cardiovascular-agents and Myocardial-Ischemia

Treatment of ischemic mitral regurgitation (IMR) is in evolution, as percutaneous procedures and complex surgical repair have been recently investigated in randomized clinical trials and matched studies. This study aims to review and compare the current treatment options for IMR.. A comprehensive literature search was conducted using electronic databases. The primary outcome was all-cause long-term mortality. The secondary outcomes were perioperative mortality, unplanned rehospitalization, reoperation, and composite end points as defined in the original articles.. A total of 12 articles met the inclusion criteria and were included in the final meta-analysis. The MitraClip procedure did not confer a significant benefit in mortality and repeated hospitalization compared with medical therapy alone. In patients with moderate IMR, the adjunct of mitral procedure over coronary artery bypass graft is not associated with clinical improvements. When evaluating mitral valve (MV) replacement versus repair, hospital mortality was greater among patients undergoing replacement (odds ratio [OR], 1.91; P = .009), but both reoperation and readmission rates were lower (OR, 0.60, P = .05; and OR, 0.45, P < .02, respectively). Comparing restrictive annuloplasty alone with adjunctive subvalvular repair, subvalvular procedures resulted in fewer readmissions (OR, 0.50; P = .06) and adverse composite end points (P = .009).. MitraClip procedure is not associated with improved outcomes compared with medical therapy. MV replacement is associated with increased early mortality but reduced reoperation rate and readmission rate compared with MV repair using annuloplasty in moderate-to-severe IMR. Despite no significant benefit in isolated outcomes comparing annular and adjunct subvalvular procedures, the adjunct of subvalvular procedures reduces the risk of major postoperative adverse events.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Female; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Hospital Mortality; Humans; Male; Middle Aged; Mitral Valve; Mitral Valve Annuloplasty; Mitral Valve Insufficiency; Myocardial Ischemia; Patient Readmission; Postoperative Complications; Prosthesis Design; Recovery of Function; Reoperation; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

Ivabradine is a unique agent that is distinct from beta-blockers and calcium channel blockers as it reduces heart rate without affecting myocardial contractility or vascular tone. Ivabradine is a use-dependent inhibitor targeting the sinoatrial node. It is approved for use in the United States as an adjunct therapy for heart rate reduction in patients with heart failure with reduced ejection fraction. In this scenario, ivabradine has demonstrated improved clinical outcomes due to reduction in heart failure readmissions. However, there has been conflicting evidence from prospective studies and randomized controlled trials for its use in stable ischemic heart disease regarding efficacy in symptom reduction and mortality benefit. Ivabradine may also play a role in the treatment of patients with inappropriate sinus tachycardia, who often cannot tolerate beta-blockers and/or calcium channel blockers. In this review, we highlight the evidence for the nuances of using ivabradine in heart failure, stable ischemic heart disease, and inappropriate sinus tachycardia to raise awareness for its vital role in the treatment of select populations.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Humans; Ivabradine; Myocardial Ischemia; Prospective Studies; Randomized Controlled Trials as Topic; Stroke Volume; Tachycardia, Sinus

Coronary microvascular dysfunction (CMD) is defined as a mismatch of myocardial blood supply and oxygen consumption due to a dysfunction of the coronary microvessels. Up to 20-30% of patients with CMD have progressive worsening of symptoms with significant impairment of quality of life. Large-scale randomized studies of the pharmacologic treatment of CMD are lacking. Classic anti-ischemic drugs are the initial form of treatment, but efficacy is often limited. Ranolazine has a unique mechanism of action that does not affect blood pressure or heart rate. When added to existing anti-anginal agents, ranolazine improved at least one domain in eight of ten studies in which a questionnaire was used to assess patient health status. Five studies evaluated coronary arterial flow reserve (CFR), reporting that patients with low values had significant improvement in CFR and suggesting that those with more severe CMD respond more favorably to ranolazine. In two studies, exercise duration and time to myocardial ischemia were significantly increased after treatment with ranolazine. Data are lacking for ranolazine use as the sole agent for CMD treatment. Some questions remain to be answered regarding ranolazine use for CMD. Larger studies of longer duration are needed to verify the effectiveness of ranolazine in the treatment of CMD.

Topics: Cardiovascular Agents; Humans; Myocardial Ischemia; Ranolazine

Translation of cardioprotective interventions aimed at reducing myocardial injury during ischaemia-reperfusion from experimental studies to clinical practice is an important yet unmet need in cardiovascular medicine. One particular challenge facing translation is the existence of demographic and clinical factors that influence the pathophysiology of ischaemia-reperfusion injury of the heart and the effects of treatments aimed at preventing it. Among these factors, age and sex are prominent and have a recognised role in the susceptibility and outcome of ischaemic heart disease. Remarkably, some of the most powerful cardioprotective strategies proven to be effective in young animals become ineffective during ageing. This article reviews the mechanisms and implications of the modulatory effects of ageing and sex on myocardial ischaemia-reperfusion injury and their potential effects on cardioprotective interventions. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.23/issuetoc.

Topics: Aging; Animals; Cardiovascular Agents; Heart; Myocardial Ischemia; Myocardial Reperfusion Injury

Contemporary data indicate that patients with signs and symptoms of ischaemia and non-obstructive coronary artery disease (INOCA) often have coronary microvascular dysfunction (CMD) with elevated risk for adverse outcomes. Coronary endothelial (constriction with acetylcholine) and/or microvascular (limited coronary flow reserve with adenosine) dysfunction are well-documented, and extensive non-obstructive atherosclerosis is often present. Despite these data, patients with INOCA currently remain under-treated, in part, because existing management guidelines do not address this large, mostly female population due to the absence of evidence-based data. Relatively small sample-sized, short-term pilot studies of symptomatic mostly women, with INOCA, using intense medical therapies targeting endothelial, microvascular, and/or atherosclerosis mechanisms suggest symptom, ischaemia, and coronary vascular functional improvement, however, randomized, controlled outcome trials testing treatment strategies have not been completed. We review evidence regarding CMD pharmacotherapy. Potent statins in combination with angiotensin-converting enzyme inhibitor (ACE-I) or receptor blockers if intolerant, at maximally tolerated doses appear to improve angina, stress testing, myocardial perfusion, coronary endothelial function, and microvascular function. The Coronary Microvascular Angina trial supports invasive diagnostic testing with stratified therapy as an approach to improve symptoms and quality of life. The WARRIOR trial is testing intense medical therapy of high-intensity statin, maximally tolerated ACE-I plus aspirin on longer-term outcomes to provide evidence for guidelines. Novel treatments and those under development appear promising as the basis for future trial planning.

Topics: Animals; Cardiovascular Agents; Clinical Decision-Making; Coronary Circulation; Coronary Vessels; Decision Support Systems, Clinical; Decision Support Techniques; Humans; Microcirculation; Microvessels; Myocardial Ischemia; Predictive Value of Tests; Treatment Outcome

Ivabradine lowers heart rate by inhibiting the hyperpolarization-activated current in pacemaker cells, and its use for the treatment of heart failure (HF) and ischemic heart disease (IHD) is well described. Ivabradine may be an attractive treatment option for other conditions for which a reduction in heart rate is desirable but less is known about its role in these settings. The primary objective was to perform a scoping review summarizing the literature evaluating novel uses for ivabradine other than HF and IHD in adults. PubMed and EMBASE were searched for articles for all dates through September 2019. Search strategies combined terms generic, commercial/trade, and international names for ivabradine. Manual search of references was also performed to identify additional articles. Studies were included if they were published in English, evaluated the efficacy of ivabradine for indications other than HF or IHD in patients aged 18 years or older, and the primary outcome included clinically relevant end points. Articles were screened first by title and abstract followed by full-text screening of the remaining articles. After removal of duplicates, 1807 records were screened for inclusion and 84 studies were included in this scoping review. Novel uses of ivabradine were reported for various tachyarrhythmias, valvular heart disease, premedication for coronary computed tomography angiography, perioperative risk reduction, sepsis with and without multi-organ dysfunction syndrome, cor pulmonale, reactive airway disease, and erectile dysfunction. This scoping review identified several potential novel uses for ivabradine in adults. This review may help to identify existing gaps where further research is needed to elucidate the role of ivabradine for indications beyond HF and IHD.

Topics: Adult; Cardiovascular Agents; Heart Failure; Heart Rate; Humans; Ivabradine; Myocardial Ischemia; Sinoatrial Node

Among the vast number of noncommunicable diseases encountered worldwide, cardiovascular diseases accounted for about 17.8 million deaths in 2017 and ischemic heart disease (IHD) remains the single-largest cause of death in countries across all income groups. Because conventional medications are not without shortcomings and patients still refractory to these medications, scientific investigation is ongoing to advance the management of IHD, and shows a great promise for better treatment modalities, but additional research can warrant improvement in terms of the quality of life of patients. Metabolic modulation is one promising strategy for the treatment of IHD, because alterations in energy metabolism are involved in progression of the disease. Therefore, the purpose of this review was to strengthen attention toward the use of metabolic modulators and to review the current level of knowledge on cardiac energy metabolic pathways.

Topics: Animals; Cardiovascular Agents; Energy Metabolism; Humans; Mitochondria, Heart; Molecular Targeted Therapy; Myocardial Ischemia; Myocytes, Cardiac

Coronary heart disease is a chronic, systemic disease with a wide range of associated symptoms, clinical outcomes, and health care expenditure. Adverse events from coronary heart disease can be mitigated or avoided with lifestyle and risk factor modifications, and medical therapy. These measures are effective in slowing the progression of atherosclerotic disease and in reducing the risk of thrombosis in the setting of plaque disruptions. With increasing effectiveness of prevention and medical therapy, the role of coronary artery revascularization has decreased and is largely confined to subgroups of patients with unacceptable angina, severe left ventricular systolic dysfunction, or high-risk coronary anatomy. There is a compelling need to allocate resources appropriately to improve prevention. Herein, we review the scientific evidence in support of medical therapy and revascularization for the management of patients with stable coronary heart disease and discuss implications for the evaluation of patients with stable angina and public policy.

Topics: Angina, Stable; Cardiovascular Agents; Disease Management; Healthy Lifestyle; Humans; Myocardial Ischemia; Review Literature as Topic; Risk Factors; Risk Reduction Behavior; Ventricular Dysfunction, Left

The goal of this study was to investigate the effects of the antianginal drugs ranolazine, nicorandil, and ivabradine on coronary microvascular function.. Electronic scientific databases were searched for randomized trials investigating the effects of antianginal drugs on coronary microvascular function. Primary outcomes were changes in the coronary flow reserve (CFR), index of microvascular resistance (IMR), and myocardial perfusion reserve index (MPRI). The secondary outcome was the Seattle Angina Questionnaire scores. The standardized mean difference or weighted mean difference (WMD) (95% CI) served as a summary statistic.. The antianginal drugs ranolazine, nicorandil, and ivabradine did not increase the CFR compared with the control drugs (standardized mean difference, 0.39; 95% CI, -0.08 to 0.85; P = 0.10). Ranolazine did not increase the global MPRI compared with the control drugs (weighted mean difference [WMD], 0.11; 95% CI, -0.06 to 0.29; P = 0.21). However, in the subgroups with a baseline CFR <2.5 or a global MPRI <2, ranolazine increased the global MPRI (WMD, 0.19; 95% CI, 0.10 to 0.27; P < 0.0001). In addition, the subendocardial midventricular MPRI (mid-subendocardial MPRI) was improved after ranolazine treatment (WMD, 0.12; 95% CI, 0.03 to 0.20; P = 0.007). Moreover, nicorandil significantly reduced the IMR compared with the control drugs (WMD, -7.63; 95% CI, -11.82 to -3.44; P = 0.0004). In addition, ranolazine and ivabradine improved 3 of the 5 Seattle Angina Questionnaire scores.. Ranolazine improved the global MPRI in patients with definite coronary microvascular dysfunction and the mid-subendocardial MPRI with suspicious coronary microvascular dysfunction, and nicorandil reduced the IMR. In addition, ranolazine and ivabradine reduced angina. Moreover, it is possible that the IMR and mid-subendocardial MPRI are more sensitive than the CFR and global MPRI for evaluating coronary microvascular function.

Topics: Angina Pectoris; Cardiovascular Agents; Coronary Artery Disease; Humans; Ivabradine; Myocardial Ischemia; Nicorandil; Randomized Controlled Trials as Topic; Ranolazine; Treatment Outcome

Cardiac remodeling is the response of the heart to a range of pathological stimuli. Cardiac remodeling is initially adaptive; however, if sustained, it ultimately causes adverse clinical outcomes. Cardiomyocyte loss or hypertrophy, inflammation and fibrosis are hallmarks of cardiac remodeling. Proteoglycans, which are composed of glycosaminoglycans and a core protein, are a non-structural component of the extracellular matrix. The lack of proteoglycans results in cardiovascular defects during development. Moreover, emerging evidence has indicated that proteoglycans act as significant modifiers in ischemia and pressure overload-related cardiac remodeling. Proteoglycans may also provide novel therapeutic strategies for further improvement in the prognosis of cardiovascular diseases.

Topics: Animals; Cardiovascular Agents; Heart Failure; Humans; Myocardial Ischemia; Proteoglycans; Ventricular Remodeling

Patients with heart failure (HF) syndromes have been categorized as those with reduced ejection fraction (EF) or preserved EF (HFpEF), and ischemia plays a key role in both types. HF remains a major cause of morbidity and mortality worldwide, and with the aging of our population this burden continues to rise, predominantly as a result of hospitalizations for HFpEF. Patients with obstructive coronary artery disease more likely have HF with reduced EF, rather than HFpEF, secondary to acute ischemic injury resulting in myocardial infarction, and large outcomes trials of treatments with neurohumoral inhibition have documented reduced adverse outcomes. In contrast, similar treatments in patients with HFpEF have not proven beneficial. This therapeutic dilemma may be attributed, in part, to heterogeneity in the underlying pathophysiology with different systemic and myocardial signaling pathways, despite similar clinical presentations and findings, in patients with HFpEF. Also, emerging evidence indicates that impaired myocardial perfusion and inflammation secondary to multiple comorbidities are key mechanisms in HFpEF. We will thoroughly review the role of ischemic heart disease in the pathogenesis of HF with reduced EF and HFpEF, and discuss the medical management strategies available for these conditions.

Topics: Cardiovascular Agents; Comorbidity; Diet, Sodium-Restricted; Healthy Lifestyle; Heart Failure; Humans; Myocardial Ischemia; Myocardial Revascularization; Recovery of Function; Risk Factors; Risk Reduction Behavior; Smoking Cessation; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Stable ischemic heart disease (SIHD) is a leading cause of death in the United States and many other countries. The defining pathobiology is an imbalance between the metabolic demands of the myocardium and its oxygen supply, which most often results from coronary artery atherosclerosis. The classic presenting symptom of SIHD is angina, but clinical presentation varies greatly among patients. Since the last In the Clinic on SIHD in 2014, several new drugs have been approved to reduce ischemic complications, such as myocardial infarction and congestive heart failure.

Topics: Cardiovascular Agents; Coronary Artery Bypass; Diagnosis, Differential; Heart Failure; Humans; Myocardial Infarction; Myocardial Ischemia; Patient Education as Topic; Risk Factors; Risk Reduction Behavior

Half of women and 1/3 of men with angina and ischemia on stress testing have ischemia with no obstructive coronary artery disease (INOCA). These patients have quality of life (QoL) impairment comparable with patients with obstructive coronary artery disease. Clinicians generally treat INOCA with traditional antianginal agents despite previous studies demonstrating variable response to these medications. We performed a systematic review to evaluate the efficacy and safety of available pharmacologic therapies for INOCA. We systematically searched the Cochrane Central Register of Controlled Trials, Embase, MEDLINE, and the World Health Organization International Clinical Trials Registry Platform in July 2017 for randomized controlled trials (RCTs) evaluating pharmacologic agents for INOCA. The primary outcome of interest was QoL. Secondary outcomes included subjective and objective efficacy measures and safety outcomes. We included 35 RCTs from 333 identified studies. Interventions that improved QoL with moderate-quality evidence included angiotensin-converting enzyme (ACE) inhibitor (±statin) and ranolazine. Low-to-very-low-quality evidence also suggests that ACE inhibitors, β blockers, calcium-channel blockers, nicorandil, ranolazine, and statins may decrease angina frequency and delay ischemia on stress testing. Other interventions, most notably nitrates, did not significantly improve any outcome. In conclusion, evidence for pharmacologic treatment of INOCA is generally poor, and higher-quality RCTs using a standardized definition of INOCA are needed. Moderate-quality evidence suggests that ACE inhibitors and ranolazine improve QoL. Other interventions had low-quality evidence or no evidence of efficacy.

Topics: Adrenergic beta-Antagonists; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Agents; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Ischemia; Nicorandil; Nitrates; Quality of Life; Ranolazine; Vasodilator Agents

Although substantial progress has been made in recent decades in reducing mortality and performing optimal revascularization in patients with myocardial infarction, ischaemic heart disease, including acute coronary syndrome, remains the leading cause of mortality worldwide. One of the remaining challenges is to better detect, prevent and treat extended myocardial damage despite angiographically optimal revascularization. Several indices are available in clinical practice to evaluate myocardial damage, infarct size and potential myocardial recovery. These indices are divided into two categories: non-invasive, generally performed after revascularization; and invasive, performed during the revascularization procedure. They allow the clinician to detect patients at risk and may help us to tailor the medical therapy and discharge strategy according to myocardial damage. Because of the number of indices, it is difficult to properly evaluate new therapeutics or to adopt one index that will provide sufficient data to better evaluate and understand the part of the coronary vasculature that is not seen - the microcirculation or so-called "black box". The aim of this review is to describe the non-invasive and invasive indices used to describe the microcirculation and their ability to predict clinical impact, and current dedicated therapeutics that may help to reduce microvascular damage and improve clinical outcomes.

Topics: Blood Flow Velocity; Cardiac Catheterization; Cardiac Imaging Techniques; Cardiovascular Agents; Coronary Circulation; Electrocardiography; Fractional Flow Reserve, Myocardial; Humans; Microcirculation; Myocardial Ischemia; Predictive Value of Tests; Prognosis; Vascular Resistance

Cardiovascular disease remains the leading cause of death among women globally, majority of which are due to ischemic heart disease. Despite the recent advances in the overall management of CVD, there are unique challenges in the diagnosis and management of women as well as poorer outcomes.. Women with ischemic cardiomyopathy experience significant morbidity and mortality. Differences in underlying pathology, delays in presentation, diagnosis, and treatment as well as the under-representation of women in clinical trials contribute to these poor outcomes. In this review, we discuss the nuances of gender-specific differences in the burden, clinical presentation, and outcomes of ischemic cardiomyopathy in women, in addition to discussion of areas needing further research.

Topics: Cardiac Rehabilitation; Cardiac Resynchronization Therapy; Cardiomyopathies; Cardiovascular Agents; Defibrillators, Implantable; Female; Healthcare Disparities; Heart-Assist Devices; Humans; Male; Myocardial Ischemia; Risk Factors; Sex Factors; Ventricular Remodeling

Shexiang Baoxin Pill (SBP) is one of the most commonly used traditional Chinese patent medicines for cardiovascular diseases. This systematic review was designed to provide rigorous therapeutic efficacy and safety evidence on the use of SBP combined with trimetazidine in elderly patients with heart failure (HF) secondary to ischaemic cardiomyopathy (ICM).. Relevant randomized controlled trials (RCTs) investigating the clinical efficacy of SBP combined with trimetazidine in treating ICM-associated HF were widely searched in electronic databases, including PubMed, Cochrane library, EMBASE, CBM, CNKI, VMIS, and Wanfang up to January 1, 2018. The methodological quality of each trial was assessed according to the Cochrane Reviewers' Handbook 5.0. Meta-analysis was performed by using Review Manager 5.3.. Eighteen RCTs (N = 1532) that met the criteria were included in the review for the assessment of methodological quality. Meta-analysis showed that, when compared with conventional therapy, SBP combined with trimetazidine significantly improved the clinical efficacy and indices of cardiac function (including increasing left ventricular ejection fraction [LVEF] and 6-minute walk distance [6-MWD], decreasing left ventricular end-diastolic diameter [LVEDD] and left ventricular end-systolic diameter [LVESD]) without serious adverse reactions.. This work provides evidence of the benefit of SBP combined with trimetazidine for the treatment of HF secondary to ICM. More high quality and well-designed RCTs are needed to confirm these findings.

Topics: Cardiovascular Agents; Drug Therapy, Combination; Drugs, Chinese Herbal; Heart Failure; Humans; Myocardial Ischemia; Randomized Controlled Trials as Topic; Trimetazidine

The prognosis of patients after acute coronary syndromes is still suboptimal, mainly due to the risk of recurrent adverse coronary events, which is greatest during the first year, but persists over one's lifetime. Meaningful progress in preventing cardiovascular events has been achieved. However, there remains much room for improvement by embracing innovative therapies and investing in multidisciplinary approaches. Pharmacological interventions focused on optimising antithrombotic and lipid-lowering therapies are both pillars of secondary prevention that have seen recent ground-breaking advances. Moreover, new approaches in diabetic patients with cardiovascular disease and new targets for anti-inflammatory treatment may significantly improve prevention strategies in the future. However, pharmacological treatments are expensive and can have significant side effects. Developing better tools in order to identify high-risk patients and promote more personalised strategies for each patient should be an absolute priority. Furthermore, adherence to medication is still low and represents a real challenge; several strategies to improve low adherence to treatment are currently under discussion. Non-pharmacological interventions are also essential. Improving communication with patients and advanced surveillance for those secondary risk factors that may negatively impact prognosis are crucial. Encouraging multidisciplinary teams that work effectively to optimise all aspects of secondary prevention, including a cardiac rehabilitation programme, is the optimal approach. Current secondary prevention strategies and suggestions for areas of improvement are discussed in this manuscript. However, the question remains: will research in secondary prevention continue to focus on stronger and more expensive drugs, or is it time for us to embrace a more patient-centred clinical and research model?

Topics: Cardiac Rehabilitation; Cardiovascular Agents; Comorbidity; Disease Progression; Humans; Myocardial Ischemia; Patient Selection; Practice Guidelines as Topic; Quality Improvement; Quality Indicators, Health Care; Recurrence; Risk Assessment; Risk Factors; Risk Reduction Behavior; Secondary Prevention; Treatment Outcome

Survivors of myocardial infarction are at risk of recurrent events and have an annual death rate of 5%. Advances in treatment and, in particular, the interventional management of myocardial infarction have seen important mortality gains over recent decades, yet cardiovascular diseases remain the biggest killer in many European countries. Change in lifestyle and adherence to medication to prevent further events are key to the recurrence of future events following myocardial infarction, but adherence to medication for the secondary prevention of cardiovascular disease is a profound problem. This article outlines a growing evidence base about the complex nature of adherence as a psychological phenomenon that is influenced by the nature of the event itself, illness perception and factors related to medication beliefs that cannot be addressed simply through a combination of educational approaches. A whole-systems approach is advocated, starting with the education of health professionals to understand the psychology of adherence, and to react comfortably to patients decisions about medication, with a pivotal role for follow-up in secondary care and cardiac rehabilitation.

Topics: Cardiovascular Agents; Disease Progression; Health Knowledge, Attitudes, Practice; Humans; Medication Adherence; Myocardial Ischemia; Patient Education as Topic; Physician-Patient Relations; Recurrence; Risk Factors; Secondary Prevention; Treatment Outcome

In 2011, for the first time in the history of humankind, non-communicable diseases became the leading cause of death worldwide. This change in trend is obviously multifactorial and very complex, as it is the paradoxical result of social, economic and health system growth worldwide. Vaccination and infectious diseases control, changing dietary habits worldwide, sedentary behaviour, globalisation, industrialisation (resulting in a shift from manual to sedentary labour), tobacco and sugary beverage surges in low- and middle-income countries and rapid urbanisation have all played a role in this epidemic transition. At the same time, the increase in cardiovascular risk factors, together with a decline in mortality in high-income countries in the past two decades, has led to a significant upsurge in the prevalence of secondary prevention of ischaemic heart disease. With this, the effect that non-adherence to cardioprotective drugs is having has become progressively clear, both in terms of clinical outcomes and as a driver of increased healthcare expenditure. The cardiovascular polypill, which was originally proposed as a strategy to improve accessibility to cardioprotective drugs worldwide, has proven to be a mainstay therapeutic approach for improving medication adherence in cardiovascular disease. In the current paper, we aim to review the need for a polypill strategy in the present scenario of cardiovascular disease, the available data that support such a strategy and the various clinical trials that are in progress that will help further shape future indications for the cardiovascular polypill.

Topics: Administration, Oral; Cardiovascular Agents; Cost-Benefit Analysis; Disease Progression; Drug Combinations; Drug Costs; Humans; Medication Adherence; Myocardial Ischemia; Recurrence; Risk Factors; Secondary Prevention; Tablets; Treatment Outcome

Personalized management of cardiovascular disorders (CVD), also referred to as personalized or precision cardiology in accordance with general principles of personalized medicine, is selection of the best treatment for an individual patient. It involves the integration of various "omics" technologies such as genomics and proteomics as well as other new technologies such as nanobiotechnology. Molecular diagnostics and biomarkers are important for linking diagnosis with therapy and monitoring therapy. Because CVD involve perturbations of large complex biological networks, a systems biology approach to CVD risk stratification may be used for improving risk-estimating algorithms, and modeling of personalized benefit of treatment may be helpful for guiding the choice of intervention. Bioinformatics tools are helpful in analyzing and integrating large amounts of data from various sources. Personalized therapy is considered during drug development, including methods of targeted drug delivery and clinical trials. Individualized recommendations consider multiple factors - genetic as well as epigenetic - for patients' risk of heart disease. Examples of personalized treatment are those of chronic myocardial ischemia, heart failure, and hypertension. Similar approaches can be used for the management of atrial fibrillation and hypercholesterolemia, as well as the use of anticoagulants. Personalized management includes pharmacotherapy, surgery, lifestyle modifications, and combinations thereof. Further progress in understanding the pathomechanism of complex cardiovascular diseases and identification of causative factors at the individual patient level will provide opportunities for the development of personalized cardiology. Application of principles of personalized medicine will improve the care of the patients with CVD.

Topics: Biomarkers; Cardiovascular Agents; Cardiovascular Diseases; Cell- and Tissue-Based Therapy; Computational Biology; Genetic Predisposition to Disease; Genomics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Life Style; Lipids; Myocardial Ischemia; Nanotechnology; Pharmacogenomic Testing; Polymorphism, Single Nucleotide; Precision Medicine; Systems Biology

Topics: Absorbable Implants; Cardiovascular Agents; Drug-Eluting Stents; Everolimus; Humans; Metals; Myocardial Ischemia; Observational Studies as Topic; Percutaneous Coronary Intervention; Prosthesis Design; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Treatment Outcome

All patients with stable ischemic heart disease (SIHD) should be managed with guideline-directed medical therapy (GDMT), which reduces progression of atherosclerosis and prevents coronary thrombosis. Revascularization is also indicated in patients with SIHD and progressive or refractory symptoms, despite medical management. Whether a strategy of routine revascularization (with percutaneous coronary intervention or coronary artery bypass graft surgery as appropriate) plus GDMT reduces rates of death or myocardial infarction, or improves quality of life compared to an initial approach of GDMT alone in patients with substantial ischemia is uncertain. Opinions run strongly on both sides, and evidence may be used to support either approach. Careful review of the data demonstrates the limitations of our current knowledge, resulting in a state of community equipoise. The ongoing ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) is being performed to determine the optimal approach to managing patients with SIHD, moderate-to-severe ischemia, and symptoms that can be controlled medically. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522).

Topics: Cardiovascular Agents; Humans; Myocardial Ischemia; Myocardial Revascularization; Percutaneous Coronary Intervention; Quality of Life; Stents

Among the innovative drugs recently introduced for the management of chronic stable angina, Ranolazine and ivabradine represent two most true innovations. In fact, even if both drugs act by reducing myocardial work and thus oxygen consumption, this happens by a peculiar mechanism unlike that of conventional antischemic drugs. Ranolazine mediates its antianginal effects by the inhibition of cardiac late sodium current. This improves myocardial relaxation favoring myocardial perfusion. Ivabradine is a selective If channel blocker and acts by reducing firing rate of pacemaker cells in the sinoatrial node, without affecting the duration of action potential. The reduction of heart rate causes a reduction of left ventricular end diastolic pressure and increases the time useful to coronary flow by a prolongation of the diastole. A body of evidence found that two drugs are useful in ischemic patients whether at rest or during exercise. In addition, they can be used in monotherapy or in association with other conventional anti-ischemic drugs. The two medications could be used with advantage also in microvascular angina when standard therapy is ineffective. Thus, the two drugs represent an adjunctive and powerful therapeutic modality for the treatment of chronic stable angina, especially when conventional antianginal drugs were insufficient or inadequate.

Topics: Angina, Stable; Benzazepines; Cardiovascular Agents; Heart Rate; Humans; Ivabradine; Myocardial Ischemia; Oxygen Consumption; Ranolazine

Pharmacologic treatment of myocardial ischemia in patients with chronic stable angina (CSA) is mainly based on heart rate lowering drugs and vasodilator agents. Other drugs are available, however, that act by some peculiar mechanism (ranolazine, trimetazidine) and may add potential anti-ischemic and anti-anginal effects to standard therapeutic mechanisms. While anti-ischemic agents are crucial for controlling angina symptoms and improving quality of life, whether myocardial ischemia portends an ominous prognosis and its suppression improves clinical outcome in CSA patients remain debated issues.

Topics: Cardiovascular Agents; Heart Rate; Humans; Myocardial Ischemia

Angina pectoris, or symptomatic myocardial ischaemia, reflects an impairment of coronary blood flow, and usually a deficiency of available myocardial energetics. Treatment options vary with the precise cause, which may vary with regards to the roles of increased myocardial oxygen demand versus reduced supply. Traditionally, organic nitrates, β-adrenoceptor antagonists, and non-dihydropyridine calcium antagonists were the only commonly used prophylactic anti-anginal agents. However, many patients failed to respond adequately to such therapy, and/or were unsuitable for their use. Areas covered: A number of 'new' agents have been shown to represent ancillary forms of prophylactic anti-anginal therapy and are particularly useful in patients who are relatively unsuitable for either percutaneous or surgical revascularisation. These include modulators of myocardial metabolic efficiency, such as perhexiline, trimetazidine and ranolazine, as well as high dose allopurinol, nicorandil and ivabradine. The advantages and disadvantages of these various agents are summarized. Expert opinion: 'Optimal' medical treatment of angina pectoris now includes use of agents primarily intended to reduce risk of infarction (e.g. statins, aspirin, ACE inhibitors). In patients whose angina persists despite the use of 'standard' anti-anginal therapy, and who are not ideal for invasive revascularization options, a number of emerging drugs offer prospects of symptomatic relief.

Topics: Angina Pectoris; Animals; Cardiovascular Agents; Drug Design; Humans; Myocardial Infarction; Myocardial Ischemia; Oxygen

Ivabradine, acting on the funny channel (If) in the sino-atrial node, reduces myocardial oxygen demand without inducing hypotension. It was developed as a specific bradycardic agent in the 1980s, avoiding the adverse effects of more traditional antianginal agents (beta-blockers and calcium channel antagonists). This has seen significant interest in this first-in-class treatment, and is perceived as a promising drug in the management of ischaemic heart disease and heart failure. There has been much clinical research conducted exploring its role in these fields, to try to elucidate potential benefits and target patient group. The side effect profile of ivabradine ensures it is well tolerated, and consistently leads to a reduction in heart rate. This review discusses the drug development and trial data in ischaemic heart disease and chronic left ventricular systolic dysfunction. Key clinical trials and observational studies are discussed in depth to examine potential explanations of unexpected or diverging results. The emerging role of ivabradine in acute decompensated heart failure is explored with recent trial data, providing a potential novel treatment avenue in this difficult to manage patient cohort. The role of intravenous ivabradine, as a beneficial tool in the acute hospital setting, when oral medication is not ideal, or where fast onset of action is required, in cardiac computerised tomography for example, is also discussed. Future directions for research are highlighted, including options for further elucidating unexplained results from previous studies.

Topics: Animals; Benzazepines; Cardiovascular Agents; Heart Failure; Heart Rate; Humans; Ivabradine; Myocardial Ischemia; Ventricular Dysfunction, Left

Ischemic heart disease (IHD) is a major cause of death and disability among Western countries and angina pectoris is the most prevalent symptomatic manifestation. Strategies to improve management of chronic stable angina are a priority. Areas covered: A comprehensive review was conducted using the Medline and Cochrane databases as well as the clinical trial databases in the United States and Europe. Traditional therapies for angina will be discussed. This review particularly emphasizes investigational therapies for angina (including pharmacological agents, cell and gene based therapies, and herbal medications). Expert opinion: There has been renewed interest in older anti-angina agents (e.g., perhexiline, amiodarone, and phosphodiestrase-5 inhibitors). Other anti-inflammatory agents (e.g., allopurinol and febuxostat) are currently undergoing evaluation for angina therapy. Therapeutic angiogenesis continues to face some challenges. Future trials should evaluate the optimum patient population that would benefit from this form of therapy.

Topics: Angina Pectoris; Angina, Stable; Cardiovascular Agents; Cell- and Tissue-Based Therapy; Drugs, Investigational; Genetic Therapy; Humans; Myocardial Ischemia

Recent large epidemiological studies have confirmed that an elevated resting heart rate is an independent predictor of cardiovascular and overall mortality in the general population as well as in patients with hypertension, coronary heart disease and chronic heart failure. Pathophysiological studies indicate that a higher heart rate has detrimental effects that favor myocardial ischemia, ventricular arrhythmias, as well as an increase in vascular oxidative stress, endothelial dysfunction and atherosclerosis progression. Benefits of heart rate lowering drugs, such as beta-blockers and ivabradine, in reducing overall and cardiovascular-related mortality, have been demonstrated particularly in patients with coronary heart disease and heart failure. However, despite these evidences, resting heart rate is still an overlooked cardiovascular risk factor.

Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Atherosclerosis; Benzazepines; Cardiovascular Agents; Clinical Trials as Topic; Heart Failure; Heart Rate; Humans; Hypertension; Ivabradine; Myocardial Ischemia; Risk Factors

Ischaemic heart disease (IHD) is the most frequent cause of mortality among men and women. Many epidemiological studies have demonstrated that premenopausal women have a reduced risk for IHD compared with their male counterparts. The incidence of IHD in women increases after menopause, suggesting that IHD is related to declining oestrogen levels. Experimental observations have confirmed the results of epidemiological studies investigating sex-specific differences in cardiac tolerance to ischaemia. Female sex appears also to favourably influence cardiac remodelling after ischaemia/reperfusion injury. Furthermore, sex-related differences in ischaemic tolerance of the adult myocardium can be influenced by interventions during the early phases of ontogenetic development. Detailed mechanisms of these sex-related differences remain unknown; however, they involve the genomic and non-genomic effects of sex steroid hormones, particularly the oestrogens, which have been the most extensively studied. Although the protective effects of oestrogen have many potential therapeutic implications, clinical trials have shown that oestrogen replacement in postmenopausal women may actually increase the incidence of IHD. The results of these trials have illustrated the complexity underlying the mechanisms involved in sex-related differences in cardiac tolerance to ischaemia. Sex-related differences in cardiac sensitivity to ischaemia/reperfusion injury may also influence therapeutic strategies in women with acute coronary syndrome. Women undergo coronary intervention less frequently and a lower proportion of women receive evidence-based therapy compared with men. Although our understanding of this important topic has increased in recent years, there is an urgent need for intensive experimental and clinical research to develop female-specific therapeutic strategies. Only then we will be able to offer patients better evidence-based treatment, a better quality of life and lower mortality.

Topics: Acute Coronary Syndrome; Androgens; Animals; Cardiovascular Agents; Disease Susceptibility; Estrogens; Evidence-Based Medicine; Female; Heart; Humans; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Sex Characteristics

The P450 enzymes (P450s) mediate the biotransformation of several drugs, steroid hormones, eicosanoids, cholesterol, vitamins, fatty acids and bile acids, many of which affect cardiovascular homeostasis. Experimental studies have demonstrated that several P450s modulate important steps in the pathogenesis of ischemic heart disease (IHD).. This article discusses the current knowledge on i) the expression of P450s in cardiovascular and renal tissues; ii) the role of P450s in the pathophysiology of IHD, in particular the modulation of blood pressure and cardiac hypertrophy, coronary arterial tone, ischemia-reperfusion injury and the metabolism of cardiovascular drugs; iii) the available evidence from observational studies on the association between P450 gene polymorphisms and risk of myocardial infarction (MI); and iv) suggestions for further research in this area.. P450s exert important modulatory effects in experimental models of IHD and MI. However, observational studies have provided conflicting results on the association between P450 genetic polymorphisms and MI. Further, adequately powered studies are required to ascertain the biological and clinical impact of P450s on clinical IHD end-points, that is, fatal and nonfatal MI, revascularization and long-term outcomes post MI. Pharmacogenetic substudies of recently completed cardiovascular clinical trials might represent an alternative strategy in this context.

Topics: Animals; Cardiovascular Agents; Cytochrome P-450 Enzyme System; Forecasting; Humans; Kidney; Myocardial Ischemia; Myocardium

Human sexuality is an important aspect of health and quality of life. Many patients with ischemic heart disease - and their partners - are concerned that sexual activity could exacerbate their cardiac condition, possibly causing myocardial infarction or cardiac death. Patients with ischemic heart disease who wish to initiate or resume sexual activity should be evaluated with a thorough medical history and physical examination. Sexual activity is reasonable for individuals with no or mild angina and those who can exercise ≥ 3-5 METS without angina, excessive dyspnea, or ischemic ST segment changes. For the patient who is considered not be at low cardiovascular (CV) risk or in whom the CV risk is unknown, an exercise stress test is reasonable in order to determine his or her exercise capacity and to ascertain if symptoms or ischemia may occur. Regular exercise and cardiac rehabilitation can be effective in reducing the risk of CV complications associated with sexual activity for the patient with ischemic heart disease.

Topics: Angina Pectoris; Cardiovascular Agents; Death, Sudden, Cardiac; Exercise Test; Humans; Myocardial Infarction; Myocardial Ischemia; Phosphodiesterase 5 Inhibitors; Risk Assessment; Sexual Behavior

Topics: Angina, Stable; Cardiovascular Agents; Diagnosis, Differential; Humans; Life Style; Myocardial Ischemia; Myocardial Revascularization; Patient Education as Topic; Practice Guidelines as Topic

Research and development in the field of coronary stent design is a fast-evolving and fascinating journey. A device that was once introduced to salvage acute closure associated with balloon angioplasty is now the standard of care for many patients with coronary artery disease. Newer generation stents are the product of remarkable progress in technology and innovation, driven by the need to make the stents easier to deliver and to improve their safety and efficacy. As such, the design of these stents has become quite sophisticated and complex. The number of available stents has increased giving patients and physicians more choices on one hand, but also created confusion in selecting the optimal stent for a given patient. Although a 'one size fits all' approach may not be reasonable, several randomized trials have attested to the efficacy and safety of newer generation durable polymer drug eluting stents. This article discusses the evidence base to support various stent choices in contemporary practice.

Topics: Acute Coronary Syndrome; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cost-Benefit Analysis; Diabetic Angiopathies; Evidence-Based Medicine; Female; Humans; Male; Myocardial Ischemia; Patient Selection; Practice Guidelines as Topic; Stents; Treatment Outcome

Coronary artery disease (CAD) is the leading cause of death worldwide. There are several presenting clinical syndromes, including sudden cardiac death. Risk factor analysis can help the primary care provider identify patients who may need more extensive evaluation or treatment. Treatment may be medical or surgical and depends on the individual patient's comorbidities and preferences. In the future, growth of new blood vessels or cardiac cells may aid in the treatment of CAD.

Topics: Biomarkers; Cardiac Catheterization; Cardiovascular Agents; Coronary Artery Disease; Creatine Kinase, MB Form; Electrocardiography; Exercise Test; Humans; Myocardial Infarction; Myocardial Ischemia; Primary Health Care; Risk Assessment; Risk Factors; Stents; Troponin

Topics: Acetanilides; Adrenergic beta-Antagonists; Angina Pectoris; Atrial Fibrillation; Benzazepines; Calcium; Calcium Channel Blockers; Cardiovascular Agents; Coronary Artery Disease; Electrocardiography; Endothelium, Vascular; Heart Failure, Diastolic; Humans; Hypercalcemia; Ivabradine; Myocardial Ischemia; Nitrates; Piperazines; Ranolazine; Sodium; Sodium Channels; Sodium-Calcium Exchanger

Percutaneous coronary intervention (PCI) decreases ischemic complications of acute coronary syndromes. The benefits of PCI in stable ischemic heart disease (SIHD) depend on its effect on quality of life (QoL), including angina, physical activity, and emotional well-being. PCI decreases angina and the need for anti-anginal medications, and increases exercise capacity and QoL, compared with baseline status and compared with medical therapy without PCI. These benefits are greater when QOL is markedly impaired by severe angina before the procedure. When considering treatment options for symptomatic SIHD, physicians should consider and provide objective data regarding QoL effects for each treatment strategy. QoL outcomes should be considered in clinical trials, appropriate use criteria, practice guidelines, and reimbursement policies for PCI.

Topics: Angina Pectoris; Cardiovascular Agents; Consensus; Coronary Artery Bypass; Emotions; Exercise Tolerance; Health Status; Humans; Mental Health; Myocardial Ischemia; Patient Selection; Percutaneous Coronary Intervention; Quality of Life; Treatment Outcome

The scientific literature clearly establishes the occurrence of cardiovascular (CV) accidents and myocardial ischemic episodes is unevenly distributed during the 24 h. Such temporal patterns result from corresponding temporal variation in pathophysiologic mechanisms and cyclic environmental triggers that elicit the onset of clinical events. Moreover, both the pharmacokinetics and pharmacodynamics of many, though not all, CV medications have been shown to be influenced by the circadian time of their administration, even though further studies are necessary to better clarify the mechanisms of such influence on different drug classes, drug molecules, and pharmaceutical preparations. Twenty-four-hour rhythmic organization of CV functions is such that defense mechanisms against acute events are incapable of providing the same degree of protection during the day and night. Instead, temporal gates of excessive susceptibility exist, particularly in the morning and to a lesser extent evening (in diurnally active persons), to aggressive mechanisms through which overt clinical manifestations may be triggered. When peak levels of critical physiologic variables, such as blood pressure (BP), heart rate (HR), rate pressure product (systolic BP × HR, surrogate measure of myocardial oxygen demand), sympathetic activation, and plasma levels of endogenous vasoconstricting substances, are aligned together at the same circadian time, the risk of acute events becomes significantly elevated such that even relatively minor and usually harmless physical and mental stress and environmental phenomena can precipitate dramatic life-threatening clinical manifestations. Hence, the delivery of CV medications needs to be synchronized in time, i.e., circadian time, in proportion to need as determined by established temporal patterns in risk of CV events, and in a manner that averts or minimizes undesired side effects.

Topics: Aortic Aneurysm; Arrhythmias, Cardiac; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiovascular Agents; Cardiovascular Diseases; Circadian Rhythm; Heart Rate; Humans; Myocardial Ischemia; Myocardium; Stroke; Takotsubo Cardiomyopathy; Time Factors

Dipeptidyl peptidase 4 (DPP-4) inhibitors (commonly referred to as gliptins) are a novel class of oral antihyperglycaemic agents with demonstrated efficacy in the treatment of type 2 diabetes mellitus (T2DM). Preclinical data and mechanistic studies have indicated a possible beneficial action on blood vessels and the heart, via both glucagon-like peptide 1 (GLP-1)-dependent and GLP-1-independent effects. DPP-4 inhibition increases the concentration of many peptides with potential vasoactive and cardioprotective effects. Clinically, DPP-4 inhibitors improve several risk factors in patients with T2DM. They improve blood glucose control (mainly by reducing postprandial glycaemia), are weight neutral (or even induce modest weight loss), lower blood pressure, improve postprandial lipaemia, reduce inflammatory markers, diminish oxidative stress, and improve endothelial function. Some positive effects on the heart have also been described in patients with ischaemic heart disease or congestive heart failure, although their clinical relevance requires further investigation. Post-hoc analyses of phase II-III, controlled trials suggest a possible cardioprotective effect with a trend for a lower incidence of major cardiovascular events with gliptins than with placebo or active agents. However, the actual relationship between DPP-4 inhibition and cardiovascular outcomes remains to be proven. Major prospective clinical trials with predefined cardiovascular outcomes and involving various DPP-4 inhibitors are now underway in patients with T2DM and a high-risk cardiovascular profile.

Topics: Animals; Biomarkers; Blood Glucose; Blood Pressure; Cardiovascular Agents; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Endothelium, Vascular; Heart Failure; Humans; Inflammation Mediators; Lipids; Myocardial Ischemia; Oxidative Stress; Risk Factors; Treatment Outcome

Non-ST elevation acute coronary syndrome (NSTE-ACS) is the commonest acute presentation of coronary artery disease (CAD). Mortality and morbidity of the condition has improved substantially over the last few decades as a result of the cumulative effect of multiple interventions acting via different mechanisms. Despite a significant increase in the rate of coronary intervention, medical therapy continues to retain a central role in the treatment of NSTE-ACS particularly in frail patients where revascularization is inappropriate or when it is incomplete. Several antiischemic agents have been used in the treatment of the condition. Beta blockers are often the first-line choice with calcium channel blockers and nitrates being used as an alternative when beta blockers are contraindicated, or as an addition to achieve optimal symptom control. Newer agents, such as nicorandil, ivabradine, and ranolazine have also been used in refractory cases. Although most of these agents have been extensively studied in large randomized controlled trials in patients with stable CAD or ST elevation acute coronary syndrome (STE-ACS), the evidence supporting their use in NSTE-ACS is less clear cut. In this article, we review various drugs available for controlling ischemia and the latest evidence in support of their use in NSTE-ACS.

Topics: Acute Coronary Syndrome; Adrenergic beta-Antagonists; Calcium Channel Blockers; Cardiovascular Agents; Evidence-Based Medicine; Humans; Myocardial Ischemia; Treatment Outcome; Vasodilator Agents

Myocardial ischemia results in a decrease in oxygen supply to the heart, leading to cardiac dysfunction. Present therapeutic strategies for treating myocardial ischemia or infarction focus on maintaining coronary artery patency by either fibrinolysis or primary percutaneous intervention. Although these approaches have dramatically improved the prognosis in patients with angina pectoris and myocardial infarction, the complication of myocardial ischemia remains a major cause of mortality and morbidity worldwide. A novel approach that entails improving and optimizing cardiac energy metabolism of the ischemic myocardium by pharmacologically manipulating different metabolic pathways in the heart holds promise in limiting myocardial damage. Metabolic support of the ischemic myocardium is aimed at increasing glycolysis and residual oxidative phosphorylation of glucose along with decreasing fatty acid oxidation. This review discusses the various metabolic modulators, both conventional and new, along with documented evidence in both acute and chronic angina.

Topics: Cardiovascular Agents; Enzyme Inhibitors; Glucose; Glycolysis; Humans; Myocardial Ischemia

Myocardial ischemia can occur without overt symptoms. In fact, asymptomatic (or silent) ST-segment depression during ambulatory electrocardiogram monitoring occurs more often than symptomatic ST-segment depression in patients with coronary artery disease. Initial studies documented that silent ischemia provided independent prediction of adverse outcomes in patients with known and unknown coronary artery disease. The ACIP (Asymptomatic Cardiac Ischemia Pilot Study) enrolled patients in the 1990s and found that revascularization was better than medical therapy in reducing silent ischemic episodes and possibly cardiovascular (CV) events. However, the more recent COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial found similar CV event rates between patients treated with optimal medical therapy alone and those treated with optimal medical therapy plus percutaneous revascularization. Therefore, in the current era, medical therapy appears to be as effective as revascularization in suppressing symptomatic ischemia and preventing CV events. COURAGE was not designed to evaluate changes in the frequency of silent ischemia. Therefore, silent ischemia may persist despite current-era treatment and might still identify patients with increased risk of CV events. Also, silent ischemia is likely to occur frequently in heart transplant patients with denervated hearts and coronary allograft vasculopathy, and future study aimed at improving the management of silent ischemia in this population is warranted. Additionally, future research is warranted to study the effect of newer medical therapies such as ranolazine or selected use of revascularization (for example, guided by fractional flow reserve) in those patients with persistent silent ischemia despite optimal current-era medical therapy.

Topics: Cardiovascular Agents; Diagnosis, Differential; Electrocardiography, Ambulatory; Exercise Test; Humans; Myocardial Ischemia; Myocardial Revascularization

Defining optimal management of patients with stable coronary artery disease continues to be a central area of debate. While it has been established that all patients with coronary artery disease should at least be managed with optimal medical therapy, many patients with stable coronary artery disease continue to be treated with revascularization, whether by percutaneous coronary intervention or coronary artery bypass grafting. What remains unclear is whether revascularization further improves outcomes when added to medical therapy. We start by reviewing trials that define optimal medical therapy. We then review results of randomized trials comparing both revascularization strategies with optimal medical therapy and assess the strengths and limitations of each. Next, we briefly describe the ongoing ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial, which will seek to determine optimal management for patients with stable ischemic heart disease in a population of patients at a uniformly higher risk prior to diagnostic cardiac catheterization. We conclude that revascularization and medical therapy should be used as complementary strategies. Available data have shown some benefits of revascularization in addition to medical therapy, but further trials are needed to better define the optimal population and magnitude and cost effectiveness of adding revascularization to optimal medical therapy.

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Combined Modality Therapy; Coronary Artery Bypass; Humans; Myocardial Ischemia; Myocardial Revascularization; Treatment Outcome

Ischemic heart disease is a significant cause of morbidity and mortality in Western society. Although interventions, such as thrombolysis and percutaneous coronary intervention, have proven efficacious in ischemia and reperfusion injury, the underlying pathological process of ischemic heart disease, laboratory studies suggest further protection is possible, and an expansive research effort is aimed at bringing new therapeutic options to the clinic. Mitochondrial dysfunction plays a key role in the pathogenesis of ischemia and reperfusion injury and cardiomyopathy. However, despite promising mitochondria-targeted drugs emerging from the laboratory, very few have successfully completed clinical trials. As such, the mitochondrion is a potential untapped target for new ischemic heart disease and cardiomyopathy therapies. Notably, there are a number of overlapping therapies for both these diseases, and as such novel therapeutic options for one condition may find use in the other. This review summarizes efforts to date in targeting mitochondria for ischemic heart disease and cardiomyopathy therapy and outlines emerging drug targets in this field.

Topics: Animals; Cardiomyopathies; Cardiovascular Agents; Disease Models, Animal; Humans; Mitochondria, Heart; Myocardial Ischemia; Treatment Outcome

Despite continuous improvements in management of patients with cancer, cardiac side-effects still account for a substantial limitation of chemotherapy. Evaluation of cardiac toxicity in patients includes consideration of biomarkers such as cardiac troponins and B-type natriuretic peptides, together with non-invasive imaging in the form of 2D-, 3D-, or strain-echocardiography, multiple gated radionuclide angiography, quantitative gated blood-pool SPECT, (123)I-metaiodobenzylguanidine scintigraphy, or cardiac magnetic resonance imaging. These approaches differ from each other with regards to availability, accuracy, sensitivity to detect early stages of cardiac injury, individual reliability, ease of use in a longitudinal follow-up perspective, and to related cost-effectiveness. Improving prevention of these cardiac side-effects depends on several, currently unresolved issues. Early detection and quantification of cardiac damage is required to adapt chemotherapy in progress for optimal management of patients. Whether increased availability of myocardial strain imaging and repeat blood biomarkers determinations will reliably and consistently achieve these goals remain to be confirmed. Also, protective approaches to reduce cardiac toxicity of anticancer drugs should be reconsidered according to the recently restricted approval for use of dexrazoxane. Anthracycline-based regimens, encapsulated anthracyclines and non-anthracycline regimens should be revisited with regards to antitumour efficacy and cardiac toxicity. Cardiovascular drugs that proved effective in prevention of anthracycline-induced cardiac toxicity in experimental models should be investigated in clinical trials. Finally, the efficacy of cardiovascular drugs that have already been tested in clinical settings should be confirmed and compared with each other in patients in increased numbers.

Topics: Anthracyclines; Antineoplastic Agents; Antioxidants; Arrhythmias, Cardiac; Biomarkers; Cardiovascular Agents; Cytotoxins; Diagnostic Techniques, Cardiovascular; Heart Diseases; Heart Failure; Heart Function Tests; Humans; Liposomes; Molecular Targeted Therapy; Myocardial Ischemia; Natriuretic Peptides; Neoplasms; Protein Kinase Inhibitors; Troponin; Ventricular Dysfunction, Left

Despite significant improvements in pharmacological therapy heart failure is still one of the leading causes for death in the Western World. The gold standard treatment of end-stage heart failure remains cardiac transplantation, but there is a great excess of eligible candidates compared with the low number of suitable donor organs. The variety of surgical organ preserving treatment strategies has significantly increased during the last 20 years, intenting either to delay or even to prevent the need for cardiac transplantation. An individually tailored surgical concept should be considered as an alternative in any heart failure patient who has reached the limits of pharmacologic therapy. This article gives an overview about current and potential future therapeutic options in end-stage heart failure.

Topics: Cardiomyopathy, Dilated; Cardiomyoplasty; Cardiovascular Agents; Combined Modality Therapy; Heart Failure; Heart Transplantation; Heart Ventricles; Heart-Assist Devices; Humans; Mitral Valve; Mitral Valve Insufficiency; Myocardial Ischemia; Myocardial Revascularization

This article contains a review of major new developments in drug treatment and the impact they could have for the general cardiologist. New treatments for arrhythmias, chronic ischemic heart disease, and secondary prevention are changing the practice of clinical cardiology. In addition, recent publications on treatment adherence and therapeutic inertia are discussed. Finally, the work of the Clinical Cardiology and Outpatient Section of the Spanish Society of Cardiology during the last year is described.

Topics: Ambulatory Care; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiology; Cardiovascular Agents; Heart Diseases; Humans; Myocardial Ischemia; Secondary Prevention

Article presents actual comparison of therapeutic methods for patients with chronic coronary artery disease and their influence on morbidity and mortality. It calls attention to the insufficiently presented fact, that invasive methods, like percutaneous and surgical revascularization, despite great expectations, have not proved to lower morbidity and mortality in large randomized studies. In contrary several groups of drugs proved their efficiency many times. Paradoxically, the cheapest approach, life style intervention, seems to be the most efficient method for prognosis improvement of patients with chronic coronary artery disease.

Topics: Cardiovascular Agents; Chronic Disease; Coronary Artery Disease; Health Behavior; Humans; Myocardial Ischemia; Myocardial Revascularization

Worldwide, the leading causes of death are ischemic heart disease and stroke. Moreover, patients with several risk factors or a history of ischemic heart disease are at a high risk of coronary event recurrence. There is evidence that primary cardiovascular disease prevention programs are effective when applied to the general population. However, therapeutic strategies designed to control several risk factors simultaneously in patients without evidence of cardiovascular disease are expensive and difficult to implement. In contrast, combination drug therapy is commonly used for secondary cardiovascular prevention and its beneficial effects on morbidity and mortality have been clearly demonstrated. Nevertheless, the actual impact of this approach is less than might be expected, partly because of poor adherence to drug regimens and the high cost of treatment in low- and middle-income countries. In patients who have had an acute myocardial infarction, the complexity of the regimen is inversely correlated ith compliance and is, in most cases, the reason for treatment discontinuation. Moreover, globally the ast majority of cardiovascular events take place in developing countries with limited health resources here access to treatment is poor. The development of fixed-dose combinations of drugs (i.e. polypills) designed for the treatment of myocardial infarction patients could help overcome these limitations, improve compliance and facilitate the distribution of and access to treatment in developing countries. We have begun a large clinical trial in five countries to investigate the beneficial effects of treatment using a polypill (i.e. aspirin, an angiotensin-converting enzyme inhibitor and a statin) on ischemic heart disease recurrence. The results of this study could provide the basis for a new therapeutic approach to the management of not only cardiovascular disease but also diabetes and stroke.

Topics: Cardiovascular Agents; Drug Combinations; Humans; Myocardial Infarction; Myocardial Ischemia; Secondary Prevention

Heart rate is a major determinant of cardiac output, myocardial oxygen consumption and coronary blood flow under physiological and pathological conditions. Experimental and clinical data have demonstrated that heart rate reduction is the main mechanism for reducing ischemia, improving left ventricular function, decreasing the risk of plaque rupture and post myocardial infarction mortality. Nowadays betablockers are the best class of drugs that can lower heart rate in patients with cardiovascular diseases, but sometimes their use is limited by some contraindications. Ivabradine is a new drug that reduces the firing rate of pacemaker cells in the sinoatrial node through a different mechanism with respect to betablockers. The purpose of this review is to investigate the main trials that support Ivabradine adoption in clinical practice.

Topics: Adrenergic beta-Antagonists; Angina Pectoris; Benzazepines; Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Cyclic Nucleotide-Gated Cation Channels; Heart Failure; Heart Rate; Humans; Ivabradine; Myocardial Ischemia; Prognosis; Sinoatrial Node

Heart failure (HF) is a syndrome causing a huge burden in morbidity and mortality worldwide. Current medical therapies for HF are aimed at suppressing the neurohormonal activation. However, novel therapies are needed for HF, independent of the neurohormonal axis, that can improve cardiac performance and prevent the progression of heart dysfunction. The modulation of cardiac metabolism may represent a new approach to the treatment of HF. The healthy heart converts chemical energy stored in fatty acids (FA) and glucose. Utilization of FA costs more oxygen per unit of ATP generated than glucose, and the heart gets 60-90% of its energy for oxidative phosphorylation from FA oxidation. The failing heart has been demonstrated to be metabolically abnormal, in both animal models and in patients, showing a shift toward an increased glucose uptake and utilization. The manipulation of myocardial substrate oxidation toward greater carbohydrate oxidation and less FA oxidation may improve ventricular performance and slow the progression of heart dysfunction. Impaired mitochondrial function and oxidative phosphorylation can reduce cardiac function by providing an insufficient supply of ATP to cardiomyocytes and by increasing myocardial oxidative stress. Although there are no effective stimulators of oxidative phosphorylation, several classes of drugs have been shown to open mitochondrial K(ATP) channels and, indirectly, to improve cardiac protection against oxidative stress. This article focuses on the energetic myocardial metabolism and oxidative status in the normal and failing heart, and briefly, it overviews the therapeutic potential strategies to improve cardiac energy and oxidative status in HF patients.

Topics: Adenosine Triphosphate; Animals; Cardiovascular Agents; Creatine Kinase, Mitochondrial Form; Fatty Acids; Glucose; Glycolysis; Heart Failure; Humans; Mitochondria, Heart; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Oxidative Phosphorylation; Oxidative Stress; Oxygen Consumption; Potassium Channels; Substrate Specificity

Coronary artery disease remains the leading cause of mortality in most industrialized countries, although age-standardized mortality related to coronary artery disease (CAD) has decreased by more than 40% during the last two decades. Coronary atherosclerosis may cause angina pectoris, myocardial infarction, heart failure, arrhythmia, and sudden death. Medical management of atherosclerosis and its manifestation aims at retardation of progression of plaque formation, prevention of plaque rupture, and subsequent events and treatment of symptoms, when these occur as well as treatment of the sequelae of the disease. Revascularization by either percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) is performed as treatment of flow-limiting coronary stenosis to reduce myocardial ischaemia. In high-risk patients with acute coronary syndromes (ACS), a routine invasive strategy with revascularization in most patients provides the best outcome with a significant reduction in death and myocardial infarction compared with an initial conservative strategy. Conversely, the benefit of revascularization among patients with chronic stable CAD has been called into question. This review will provide information that revascularization exerts favourable effects on symptoms, quality of life, exercise capacity, and survival, particularly in those with extensive CAD and documented moderate-to-severe ischaemia. Accordingly, CABG and PCI should be considered a valuable adjunct rather than an alternative to medical therapy.

Topics: Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chronic Disease; Coronary Artery Bypass; Coronary Artery Disease; Female; Humans; Incidence; Male; Middle Aged; Myocardial Ischemia; Myocardial Revascularization; Prevalence; Risk Assessment; Stents

Angina pectoris, the pain of myocardial ischemia, is the major initial and subsequent presentation of coronary disease in women. Angina in women is associated with more adverse morbidity, mortality, and quality-of-life outcomes than for men, despite women having less obstructive coronary artery disease and better left ventricular function. Women with chest pain and myocardial ischemia, in the absence of significant obstructive disease of the coronary arteries, have prominent morbidity and mortality outcomes; the postulated mechanism is microvascular disease. Women also have more non-chest pain manifestations of myocardial ischemia than men. These variables must be incorporated in assessments of optimal diagnostic and therapeutic strategies for myocardial ischemia in women.

Topics: Angina Pectoris; Cardiovascular Agents; Chest Pain; Coronary Disease; Coronary Vessels; Female; Humans; Myocardial Ischemia; Prognosis; Quality of Life; Risk Factors; United States

A wealth of data suggests that heart rate (HR) is an independent predictor of cardiovascular and all-cause mortality in men and women of all ages with and without cardiovascular disease. Data gathered from clinical trials suggest that HR reduction is an important mechanism of benefit of HR-lowering drugs. A high HR has direct detrimental effects not only on myocardial ischemia but also on the progression of atherosclerosis, ventricular arrhythmias, and on left ventricular function. The risk increases with HR >60 b.p.m. Ivabradine, a drug that slows HR though an effect on the If channels, has been approved for the control of myocardial ischemia in patients with coronary artery disease intolerant to beta-blockers. More recently, the indication of ivabradine has been extended for use in association with beta-blockers in patients with coronary artery disease. The effects of ivabradine on myocardial ischemia are greater than those predicted by pure HR reduction with beta-blockers, suggesting additional mechanisms of action.

Topics: Adrenergic beta-Antagonists; Benzazepines; Cardiovascular Agents; Coronary Artery Disease; Heart Rate; Humans; Ivabradine; Myocardial Ischemia; Randomized Controlled Trials as Topic

We focus on the molecular and cellular basis of the improvement in myocardial energetics, which might represent an attractive therapeutic option in some forms of acute and chronic heart disease.. Myocardial dysfunction, whether related to left ventricular hypertrophy, heart failure or myocardial ischaemia, is frequently associated with impairment of myocardial energy balance. It is now apparent that this energetic impairment plays a pivotal role, not only in the evolution and outcomes of these disorders but also frequently in their pathogenesis. Despite the fact that energetic impairment may arise for many complex reasons, and the difficulty both in assessing the impairment in vivo and in determining its precise mechanism(s), a number of drugs have become available for treatment of ischaemia and heart failure, as well as potentially for limitation of pathological left ventricular hypertrophy, which act primarily by altering myocardial metabolism so as to improve energetic status. Recent studies with perhexiline and trimetazidine, agents which induce a 'metabolic shift' from long-chain fatty acid to glucose utilization, have demonstrated the utility of this therapeutic principle.. There is ongoing need for more complete mechanistic understanding of the 'metabolic agents', as well as for the large-scale clinical trials of their impact on health outcomes.

Topics: Acetanilides; Amiodarone; Cardiovascular Agents; Heart Failure; Humans; Hypertrophy, Left Ventricular; Myocardial Ischemia; Myocardial Perfusion Imaging; Myocardial Reperfusion; Myocardium; Perhexiline; Piperazines; Ranolazine; Trimetazidine; Vasodilator Agents

Microvascular obstruction (MVO) commonly occurs following percutaneous coronary interventions (PCI), may lead to myocardial injury, and is an independent predictor of adverse outcome. Severe MVO may manifest angiographically as reduced flow in the patent upstream epicardial arteries, a situation that is termed "no-reflow." Microvascular obstruction can be broadly categorized according to the duration of myocardial ischemia preceding PCI. In "interventional MVO" (e.g., elective PCI), obstruction typically involves myocardium that was not exposed to acute ischemia before PCI. Conversely "reperfusion MVO" (e.g., primary PCI for acute myocardial infarction) occurs within a myocardial territory that was ischemic before the coronary intervention. Interventional and reperfusion MVO have distinct pathophysiological mechanisms and may require individualized therapeutic approaches. Interventional MVO is triggered predominantly by downstream embolization of atherosclerotic material from the epicardial vessel wall into the distal microvasculature. Reperfusion MVO results from both distal embolization and ischemia-reperfusion injury within the subtended ischemic tissue. Management of MVO and no-reflow may be targeted at different levels: the epicardial artery, microvasculature, and tissue. The aim of the present report is to advocate a systematic approach to prevention and treatment of MVO in different clinical settings. Randomized clinical trials have studied strategies for prevention of MVO and no-reflow; however, the efficacy of measures for reversing MVO once no-reflow has been demonstrated angiographically is unclear. New approaches for prevention and treatment of MVO will require a better understanding of intracellular cardioprotective pathways such as the blockade of the mitochondrial permeability transition pore.

Topics: Angioplasty, Balloon, Coronary; Animals; Cardiovascular Agents; Coronary Circulation; Embolism; Evidence-Based Medicine; Filtration; Humans; Ischemic Preconditioning, Myocardial; Microcirculation; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; No-Reflow Phenomenon; Treatment Outcome

Premenopausal females have a comparably lower incidence of cardiovascular disease than their male counterparts. Although estrogen and activation of estrogen receptors (ERs) have been found to contribute to female protection, the complex mechanisms involved are unclear. Besides altering gene transcription, estrogen could elicit its cardioprotective effect via ER-mediated nongenomic signaling pathways. In addition to the two classic nuclear ER isoforms, ERα and ERβ, a G-protein coupled ER (GPR30 or GPER) has been found to be expressed in cardiomyocytes and plays an acute cardioprotective role in ischemia reperfusion injury. By using isoform-specific ER knockout mouse models and/or their specific modulators, the mechanisms of the different ERs involved in cardioprotection have been explored. In this review, we will focus on the signaling pathways leading to cardioprotection in ischemia reperfusion injury after ER activation and discuss the possibility and promise of specific ER modulators to treat ischemic heart diseases.

Topics: Animals; Cardiovascular Agents; Estrogen Receptor alpha; Estrogen Receptor beta; Female; Humans; Male; Mice; Mice, Knockout; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Selective Estrogen Receptor Modulators; Sex Factors; Signal Transduction

Not only the prevalence, but also the mortality due to ischaemic cardiovascular disease is higher in older than in young humans, and the demographic shift towards an ageing population will further increase the prevalence of age-related cardiovascular disease. In order to develop strategies aimed to limit reversible and irreversible myocardial damage in older patients, there is a need to better understand age-induced alterations in protein expression and cell signalling. Cardioprotective phenomena such as ischaemic and pharmacological pre and postconditioning attenuate ischaemia/reperfusion injury in young hearts. Whether or not pre and postconditioning are still effective in aged organs, animals, or patients, i.e. under conditions where such cardioprotection is most relevant, is still a matter of debate; most studies suggest a loss of protection in aged hearts. The present review discusses changes in protein expression and cell signalling important to ischaemia/reperfusion injury with myocardial ageing. The efficacy of cardioprotective manoeuvres, e.g. ischaemic pre and postconditioning in aged organs and animals will be discussed, and the development of strategies aimed to antagonize the age-induced loss of protection will be addressed.

Topics: Age Factors; Aging; Animals; Cardiovascular Agents; Cytoprotection; Humans; Ischemic Preconditioning, Myocardial; Mitochondria, Heart; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Signal Transduction; Treatment Outcome

Morbidity of patients with cardiac syndrome X (typical anginal-like chest pain and normal coronary arteriogram) is high with continuing episodes of chest pain and frequent hospital readmissions. Management of this syndrome represents a major challenge for the treating physician. Conventional therapies with antianginal agents such as nitrates, calcium channel antagonists, classic beta-adrenoceptor blockers and nicorandil have been tried, with variable success. However, this might be related to a failure to target the underlying pathophysiology and, clearly, more effective therapies are needed. Supporting evidence for the important role of endothelial dysfunction and oxidative stress in the pathogenesis of cardiac syndrome X has come from the recent observation that basal superoxide production predicts future cardiovascular events in this patient group. This review will discuss the pathophysiology, current medical management and potential new pharmacological treatment for patients with cardiac syndrome X which target endothelial dysfunction and oxidative stress. What's already known about this topic? Morbidity of patients with cardiac syndrome X is high. The important role of endothelial dysfunction and oxidative stress in the pathogenesis of cardiac syndrome X. What does this article add? This review will discuss the pathophysiology, current medical management and potential new pharmacological treatment for patients with cardiac syndrome X which target endothelial dysfunction and oxidative stress.

Topics: Animals; Antioxidants; Cardiovascular Agents; Cognitive Behavioral Therapy; Endothelium, Vascular; Estrogen Replacement Therapy; Estrogens; Exercise; Humans; Inflammation; Insulin Resistance; Microcirculation; Microvascular Angina; Myocardial Ischemia; Oxidative Stress; Treatment Outcome

LA-419, currently being developed by Lacer SA, is a thiol-containing analog of isosorbide mononitrate that is undergoing assessment in clinical trials for the treatment of chronic ischemic cardiovascular disorders. The compound was originally designed to have a reduced tendency toward tolerance sensitivity - a major limitation of established organic nitrate compounds. The rationale behind the drug design was to include an antioxidant moiety in the drug structure to combat the contribution of oxidative stress in tolerance induction. The compound is at an early stage of development, but has already provided some surprising data. First, LA-419 does not appear to require the nitroxy ester moiety for activity and its actions might not be mediated only by nitric oxide release. Second, unlike conventional nitrates, LA-419 is active in platelets, suggesting a potential role as an antithrombotic agent. Third, LA-419 has a profound impact on left ventricular hypertrophy, making the drug a plausible candidate for several additional potential therapeutic opportunities. In addition, LA-419 has demonstrated potential in the treatment of glaucoma and intestinal disorders. At the time of publication, LA-419 was in phase II clinical trials in patients with chronic ischemic cardiovascular disorders.

Topics: Animals; Antioxidants; Cardiovascular Agents; Cardiovascular Diseases; Disease Models, Animal; Drug Tolerance; Fibrinolytic Agents; Humans; Hypertrophy, Left Ventricular; Isosorbide Dinitrate; Myocardial Ischemia; Nitric Oxide Donors; Patents as Topic; Structure-Activity Relationship; Treatment Outcome

Infarct size can be limited by reducing the determinants of infarct size or increasing collateral blood flow by treatment initiated before the ischaemic event. Reperfusion is the definitive treatment for permanently reducing infarct size and restoring some degree of contractile function to the affected myocardium. Innate survival mechanisms in the heart can be stimulated by short, non-lethal periods of ischaemia and reperfusion, applied either before or after the ischaemic event. Preconditioning, a series of transient intervals of ischaemia and reperfusion applied before the lethal 'index' ischaemic event, sets in motion molecular and cellular mechanisms that increase cardiomyocyte survival to a degree that had not hitherto been seen before. The cardioprotective ischaemic-reperfusion protocol applied at onset of reperfusion, termed 'postconditioning' (Postcon), is also associated with significant cardioprotection that can be applied at the point of reperfusion treatment in the catheterization laboratory or operating room. Both preconditioning and Postcon have been successfully applied to the clinical setting and have been found to reduce infarct size and other attributes of post-ischaemic injury. This review will summarize the physiological preclinical data on preconditioning and Postcon that are relevant to their translation to clinical therapeutics and treatment.

Topics: Animals; Cardiovascular Agents; Cell Survival; Humans; Ischemic Preconditioning, Myocardial; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Treatment Outcome

Coronary artery disease (CAD) is a leading cause of mortality and morbidity in most developed countries. Gender-related differences have been found in the presentation, prevalence, and clinical outcomes of CAD in many studies. Compared to women, men present with ST-segment elevation myocardial infarction more often and have a higher prevalence of CAD. These findings indicate that gender may have an important influence on CAD. Appropriate diagnosis, prevention, recent patent inventions, and treatment will improve the care of all patients. It is therefore necessary to consider the differences in the features of ischemic heart disease between men and women when examining patients. Novel drugs for tailor-made therapy based on gender differences should be developed for the treatment of CAD in future.

Topics: Animals; Cardiovascular Agents; Female; Humans; Male; Myocardial Ischemia; Prevalence; Sex Characteristics

Although advances in percutaneous catheter-based interventions (PCI) for coronary artery disease have been associated with reductions in angiographic as well as clinical restenosis, no consistent reduction in the occurrence of death or nonfatal myocardial infarction (MI) has been observed either between devices (balloon vs bare-metal stent vs drug-eluting stent [DES]) or between device and medically treated patients with chronic stable coronary disease. Objective evidence of myocardial ischemia--irrespective of the methodology used to demonstrate its presence--is qualitatively and quantitatively related to the occurrence of death and/or nonfatal MI. The magnitude of ischemia is directly proportional to the magnitude of revascularization benefit (reduction in death or MI). Revascularization by PCI is more effective in reducing ischemia than medical therapy alone. The evolution of both PCI technology (DES) and adjunctive pharmacology has improved the relative magnitude and durability of PCI benefit compared with medical therapy alone.

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Clinical Trials as Topic; Combined Modality Therapy; Coronary Artery Disease; Evidence-Based Medicine; Humans; Multicenter Studies as Topic; Myocardial Infarction; Myocardial Ischemia; Patient Selection; Risk Assessment; Time Factors; Treatment Outcome

Antianginal and lipid-lowering medications may modify the results of stress myocardial perfusion imaging. Several studies have shown the beneficial potential of these agents in suppressing myocardial ischemia in patients with known coronary artery disease. The effects of nitrates, calcium-channel blockers, beta-blockers, and statins on myocardial perfusion imaging are likely attributable to changes in myocardial blood flow and myocardial oxygen supply-demand ratio. This comprehensive review examines relevant experimental and clinical published data. Technical issues in image interpretation specific to myocardial perfusion imaging and implications of use of cardiac medications to results of myocardial perfusion imaging are discussed.

Topics: Adrenergic beta-Antagonists; Calcium Channel Blockers; Cardiovascular Agents; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Ischemia; Nitroglycerin; Positron-Emission Tomography; Stroke Volume; Tomography, Emission-Computed, Single-Photon

Atrial fibrillation occurs and maintains itself in the context of a morphologically and functionally altered atrial substrate that can be induced by stressors such as underlying diseases (cardiac or noncardiac) or aging. The resultant structural remodeling is a slow process that progressively affects myocytes and the myocardial interstitium, and takes place from as early as the first days of atrial tachyarrhythmia. The left atrium, and particularly its posterior wall, is the location where remodeling is concentrated to the greatest extent. The mechanisms that underlie the remodeling process in atrial fibrillation have not yet been completely elucidated, although experimental and clinical investigations have indicated a number of signaling systems, inflammation, oxidative stress, atrial stretching and ischemia as factors involved in the cascade of events that leads to atrial fibrillation. The aim of this Review is to provide a comprehensive overview of the morphological changes that characterize the fibrillating atrial myocardium at histological and ultrastructural levels, and the established and hypothetical pathogenetic mechanisms involved in structural remodeling. This article also highlights the emerging therapies being developed to prevent progression of atrial fibrillation.

Topics: Animals; Atrial Fibrillation; Atrial Function; Cardiovascular Agents; Catheter Ablation; Cell Death; Connexins; Disease Models, Animal; Disease Progression; Fibrosis; Heart Atria; Humans; Inflammation; Myocardial Ischemia; Myocardium; Oxidative Stress; Risk Factors; Tachycardia, Supraventricular; Treatment Outcome

Erectile dysfunction (ED) is a sensitive indicator of wider arterial insufficiency and an early correlate for the presence of ischemic heart disease. Among patients with coronary artery disease, prevalence reports of ED range from 42% to 75%. The US Food and Drug Administration has approved 3 phosphodiesterase-5 (PDE-5) inhibitors for treatment of male sexual dysfunction: sildenafil, tadalafil, and vardenafil. PDE-5 inhibitors also have cardiovascular effects. They inhibit PDE-5 enzymes in pulmonary vasculature, which causes vasodilation that decreases pulmonary vascular pressure. Sildenafil is approved for treatment of patients with pulmonary hypertension. PDE-5 inhibition with sildenafil improves cardiac output by balancing pulmonary and systemic vasodilation, and augments and prolongs the hemodynamic effects of inhaled nitric oxide in patients with chronic congestive heart failure and pulmonary hypertension. In vivo and in vitro studies are examining the possible beneficial effects of PDE-5 inhibitors in conditions such as myocardial infarction and endothelial dysfunction.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Heart Failure; Humans; Hypertension, Pulmonary; Male; Myocardial Ischemia; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Treatment Outcome

Metabolic modulation during myocardial ischemia is possible by the use of specific drugs, which may induce a shift from free fatty acid towards predominantly glucose utilization by the myocardium to increase ATP generation per unit oxygen consumption. Three agents (trimetazidine, ranolazine, and perhexiline) have well-documented anti-ischaemic effects. However, perhexiline, the most potent agent currently available, requires plasma-level monitoring to avoid hepato-neuro-toxicity. Besides, the long-term safety of trimetazidine and ranolazine has yet to be established. In addition to their effect in ischemia, the potential use of these drugs in chronic heart failure is gaining recognition as clinical and experimental data are showing the improvement of myocardial function following treatment with several of them, even in the absence of ischemia. Future applications for this line of treatment is promising and deserves additional research. In particular, large, randomised, controlled trials investigating the effects of these agents on mortality and hospitalization rates due to coronary artery disease are needed.

Topics: Animals; Cardiovascular Agents; Humans; Ischemic Preconditioning, Myocardial; Myocardial Ischemia; Myocardium

The last few decades have seen significant advancement in the therapy of Ischemic Heart Diseases (IHD). This is a direct outcome of the increasing knowledge of the molecular mechanisms involved during an ischemic insult of the myocardium. Even then there is still a major unmet need for better strategies or drug therapies to reduce ventricular remodeling and improve post-ischemic myocardial function. The ex-vivo isolated working heart model and the in vivo myocardial infarction model are the best known techniques to elucidate the contribution of a drug therapy to confer cardioprotection in the event of an ischemic insult/reperfusion. Our review aims to provide an insight into the state of the art techniques that lay the foundations for cardiovascular drug discovery and present the prospects for further development from a preclinical perspective. The first section of the review provides an overview of the rat/mouse ex-vivo and in vivo models of myocardial ischemia. The following section will then present various applications of these clinically relevant models in characterizing cardiac functions, screening for drugs and identifying the drug induced changes in cardiac functions. Finally the role of these models in drug development is discussed with respect to functional relevance of drug treatment on heart rate, aortic flow, coronary flow, infarct size and the mechanisms by which these drugs promote myocardial protection. This review may serve as a basic knowledge for researchers who intend to study the efficacy of a drug in the treatment of ischemic heart diseases.

Topics: Animals; Cardiotonic Agents; Cardiovascular Agents; Disease Models, Animal; Drug Discovery; In Vitro Techniques; Mice; Myocardial Ischemia; Perfusion; Rats; Reperfusion Injury; Technology, Pharmaceutical; Ventricular Remodeling

Apoptosis, a form of programmed cell death (PCD), plays an important role in the initiation and progression of a number of cardiovascular disease, such as heart failure, myocardial infarction, and atherosclerosis. One of the most prominent characteristics of apoptosis is the externalisation of phosphatidylserine (PS), a plasma cell membrane phospholipid, which in healthy cells only is present on the inner leaflet of the plasma cell membrane. Annexin A5, a 35 kD plasma protein, has strong affinity for PS in the nano-molar range. Through the coupling of Annexin A5 to contrast agents, visualization of apoptotic cell death in vivo in animal models and in patients has become feasible. These imaging studies have provided novel insight into the extent and kinetics of apoptosis in cardiovascular disease. Furthermore, Annexin A5 imaging has proven to be a suitable imaging biomarker for the evaluation of cell death modifying compounds and plaque stabilizing strategies. Recent insight in PS biology has shown that PS externalisation not only occurs in apoptosis, but is also observed in activated macrophages and stressed cells. In addition, it has been shown that Annexin A5 not only binds to exteriorized PS, but is also internalized through an Annexin A5 specific mechanism. These latter findings indicate that Annexin A5 imaging is not exclusively valuable for apoptosis detection, but can also be used to visualize inflammation and cell stress. This will open novel opportunities for imaging and drug delivery strategies. In this review we will discuss the introduction of Annexin A5 in preclinical and clinical imaging studies and provide an outlook on novel opportunities of Annexin A5 based targeting of PS.

Topics: Animals; Annexin A4; Annexin A5; Apoptosis; Atherosclerosis; Biomarkers; Cardiovascular Agents; Cardiovascular Diseases; Disease Models, Animal; Fluorescent Dyes; Heart Failure; Humans; Microscopy, Fluorescence; Myocardial Ischemia; Radiopharmaceuticals; Risk Assessment; Swine; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

The indications for percutaneous coronary intervention (PCI) continue to evolve because of the steady improvement in technology, broadened patient and lesion selection criteria, and new evidence from clinical trials. Recently, the role of PCI in patients with chronic stable angina has received considerable scrutiny and has been the subject of great controversy. In these patients, the goals of therapy include the relief of symptom, treatment of ischemia, and reducing the need for subsequent interventions. Medical therapy is the cornerstone in the management of coronary artery disease and should be optimized in all patients. The COURAGE trial investigated the efficacy of combined PCI and optimal medical therapy (OMT) versus OMT alone in patients with stable disease. The trial confirmed several issues that have been already well delineated: (1) in low risk patients, the hard endpoints of death and MI are relatively infrequent and are not reduced by PCI - for prevention of these, OMT may be sufficient, (2) crossover from OMT to PCI is frequent, even in low risk patients, (3) PCI is very effective in reducing symptoms and myocardial ischemia, and (4) significant untreated ischemia is associated with greater likelihood of death and MI.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Clinical Trials as Topic; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Outcome Assessment, Health Care; Radiography; Research Design

Angina pectoris can result in an imbalance between oxygen supply and demand of the heart muscle, resulting in a compromised energy supply to the heart muscle. Currently, the primary approach to treating angina is aimed either at decreasing muscle oxygen demand, or increasing oxygen supply to the muscle. An alternative approach is to increase cardiac efficiency by increasing the amount of cardiac work at a given level of oxygen consumed. This can be achieved by inhibiting myocardial fatty acid oxidation, which leads to an increase in glucose oxidation. Consequently, lactate and proton production decrease, and as a result cardiac efficiency is improved. The approach of partial fatty acid oxidation (pFOX) inhibition is beneficial in the treatment of angina pectoris, both as a monotherapy and when used in combination with conventional therapy. pFOX inhibitors not only lessen the severity and symptoms of an angina attack, they also decrease the incidence of angina attacks in patients with coronary artery disease. The approach of optimizing energy substrate preference in the heart is a new and effective approach to treating angina pectoris.

Topics: Angina Pectoris; Animals; Cardiovascular Agents; Coronary Artery Disease; Energy Metabolism; Fatty Acids; Humans; Myocardial Contraction; Myocardial Ischemia; Oxidation-Reduction

Coronary artery bypass grafting (CABG) has played an important role in the treatment of ischemic heart disease. Recently, the introduction of a drug-eluting stent (DES) has decreased the incidence of restenosis after percutaneous intervention (PCI). PCI with a DES is being increasingly performed, whereas the number of patients for whom CABG has been indicated has decreased over the last few years in Japan and the United States. According to a report, the number of patients undergoing CABG will not decrease in the future due to its usefulness in the treatment of multi-vessel lesions. We have also reviewed how CABG should be improved. For this purpose, it may be important to carry out less invasive CABG by the off-pump method and to improve the long-term results obtained by CABG with an internal thoracic artery graft and complete revascularization. Hence, CABG may achieve better long-term results compared with PCI and continued future application of CABG.

Topics: Angioplasty, Balloon, Coronary; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Coronary Artery Bypass; Coronary Restenosis; Humans; Myocardial Ischemia; Stents

Several studies have revealed varying degrees of changes in sarcoplasmic reticular and myofibrillar activities, protein content, gene expression and intracellular Ca-handling during cardiac dysfunction due to ischemia-reperfusion (I/R); however, relatively little is known about the sarcolemmal and mitochondrial alterations, as well as their mechanisms in the I/R hearts. Because I/R is associated with oxidative stress and intracellular Ca-overload, it has been indicated that changes in subcellular activities, protein content and gene expression due to I/R are related to both oxidative stress and Ca-overload. Intracellular Ca-overload appears to induce changes in subcellular activities, protein contents and gene expression (subcellular remodeling) by activation of proteases and phospholipases, as well as by affecting the genetic apparatus, whereas oxidative stress is considered to cause oxidation of functional groups of different subcellular proteins in addition to modifying the genetic machinery. Ischemic preconditioning, which is known to depress the development of both intracellular Ca-overload and oxidative stress due to I/R, was observed to attenuate the I/R-induced subcellular remodeling and improve cardiac performance. It is suggested that a combination therapy with antioxidants and interventions, which reduce the development of intracellular Ca-overload, may improve cardiac function by preventing or attenuating the occurrence of subcellular remodeling due to ischemic heart disease. It is proposed that defects in the activities of subcellular organelles may serve as underlying mechanisms for I/R-induced cardiac dysfunction under acute conditions, whereas subcellular remodeling due to alterations in gene expression may explain the impaired cardiac performance under chronic conditions of I/R.

Topics: Animals; Antioxidants; Calcium; Cardiovascular Agents; Humans; Ischemic Preconditioning, Myocardial; Mitochondria, Heart; Myocardial Ischemia; Myocardium; Oxidative Stress; Reperfusion Injury; Sarcolemma; Ventricular Function; Ventricular Remodeling

Several systemic and cardiac diseases cause an impairment of left ventricular filling or of the ability to maintain cardiac output, without an increase in end-diastolic pressure. Prevalence of diastolic dysfunction has been found to be higher than systolic dysfunction in most studies. Many physiological conditions (age, sex and body weight), and pathological processes, such as cardiac or systemic diseases, can increase the incidence of diastolic dysfunction. Early diagnosis of left ventricular diastolic impairment has been demonstrated to have important therapeutic implications. Several invasive or non-invasive methods to investigate diastolic properties of the left ventricle have been described; a large number of studies compared different parameters of diastolic function in order to find the most accurate: this is of particular prognostic relevance since diastolic dysfunction may remain asymptomatic for a long period before resulting in overt heart failure. The purpose of this article is to provide an extensive review of the contemporary literature regarding diastolic function assessment and its role in daily practice.

Topics: Acute Disease; Angiotensin-Converting Enzyme Inhibitors; Cardiac Output, Low; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Diabetes Complications; Diastole; Echocardiography; Humans; Hypertension; Myocardial Ischemia; Pericarditis; Renin-Angiotensin System; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Cardiovascular Agents; Cardiovascular Diseases; Female; Humans; Male; Myocardial Ischemia

In patients with acute coronary syndromes (ACS), hypertension is common. The type of ACS and severity of hypertension would determine the treatment algorithm. In ST elevation myocardial infarction (MI), time to reperfusion is essential whereas in malignant hypertension the reduction of blood pressure to prevent end organ damage is the priority. Many therapeutic drugs available for ACS and hypertension are commonly used to treat both these conditions simultaneously. Once the ACS is treated medically, revascularization therapy is likely to be considered. Importantly, optimization of hypertension management may prevent subsequent complications. In this review, we discuss the frequency of hypertension and ACS as single clinical conditions, as well as combined presentations. The pathophysiology of myocardial perfusion in hypertensive patients and the effect of blood pressure (BP) normalization is discussed. This review focuses on treatment strategies from a non-interventional and interventional perspective. Finally, current medications used in treating hypertension in ACS will be compared with regards to their mode of action and prognostic value.

Topics: Cardiovascular Agents; Disease Management; Humans; Hypertension; Myocardial Ischemia; Myocardial Revascularization

Cardiovascular diseases, the clinical paradigm of atherosclerosis, are the primary cause of mortality in developed countries. The origin of the atheromatous lesion is multifactorial, as it is the therapeutic approach to its prevention and clinical complications. The initial symptoms of ischemia in a vascular bed are usually evident when the atherosclerotic process is very advanced, being indicative of a diffuse disease and of an elevated future risk for ischemic events in other vascular territories. We perform this review in this clinical scenario, highlighting the preventive and therapeutic aspects of demonstrated clinical efficacy, with no detail of those treatments with benefit insufficiently proven.

Topics: Angina Pectoris; Anticoagulants; Atherosclerosis; Brain Ischemia; Cardiovascular Agents; Combined Modality Therapy; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Infarction; Myocardial Ischemia; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Risk Factors

Stable angina pectoris is a manifestation of ischemic heart disease which frequently leeds to acute coronary syndrome. The patient has a short effort or stress situation induced retrosternal pain which is easing after the elimination of its cause, or taking nitroglycerin. Several new data have appeared in the literature about the pathogenesis and diagnosis of stable angina pectoris. Due to the international guidelines using the new drugs and revascularisation techniques, the primary and secondary prevention of stable angina pectoris was improved.

Topics: Acute Disease; Angina Pectoris; Angina, Unstable; Cardiovascular Agents; Humans; Myocardial Ischemia; Syndrome

Immunopharmacological studies show that medicines used in cardiovascular diseases (atherosclerosis, ischaemic heart disease, heart failure) can exert immunomodulatory effects on proinflammatory cytokines. In the paper the influence of statins, fibrates, angiotensin converting enzyme inhibitors (ACEI), beta-blockers, calcium channel blockers and phosphodiesterase inhibitors on the activity of cytokines was introduced.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Atherosclerosis; Calcium Channel Blockers; Cardiovascular Agents; Cardiovascular Diseases; Cytokines; Heart Failure; Humans; Immunologic Factors; Myocardial Ischemia; Phosphodiesterase Inhibitors

Topics: Aged; Cardiovascular Agents; Geriatric Assessment; Humans; Myocardial Ischemia

To describe the use of ischaemic heart disease (IHD) secondary prevention measures in the Spanish National Health System.. Systematic review of observational studies with information on the use of preventive treatment and measures in the prevention of secondary IHD.. Primary care and specialised out-patient clinics.. Medline search and complementary searches of studies published between 1995 and 2004 with a description of the use secondary prevention measures on hospital discharge or in the follow up after discharge.. A total of 125 references were found after the MEDLINE search, 13 of which were selected after an independent review by 2 researchers. The complementary sources provided 9 more studies giving a total of 22.. One researcher extracted information on the characteristics of the study and the results variables, which were independently verified by a second evaluator. RESULTS. In the 22 studies found, a high level of variation was shown in the different treatment rates: anti-aggregants (at discharge, 72%-97.1%; follow-up, 46.4%-93.8%); beta-blockers (at discharge, 29%-68.3%; follow-up, 22.4%-59.0%); drugs with action on the renin-angiotensin system (at discharge, 16.2%-52.2%; follow-up, 6.1%-53.1%); lipid lowering drugs (at discharge, 6.7%-88.7%; follow-up, 24.5%-89.5%). The treatment rates showed a progressive improvement over time during the period studied.. In the period 1994-2003 treatment rates in the secondary prevention of IHD have increased, although there is still much room for improvement.

Topics: Cardiovascular Agents; Clinical Trials as Topic; Epidemiologic Studies; Humans; Myocardial Ischemia; Spain

The management of coronary artery disease should always include life style modification, control of cardiovascular risk factors and drugs with proven prognostic efficacy, i.e. antiplatelet drugs, statins, ss-blockers and, in most cases, ACE-inhibitors. Nitrates, sometimes also calcium antagonists, are used to control the symptoms of angina pectoris. Revascularisation by percutaneous treatment (stent implantation) or bypass surgery is indicated in patients with large areas of ischemia during stress testing or with high risk coronary anatomy during angiography, especially with reduced ventricular function, or when the angina cannot be adequately controlled by medicinal management. Single vessel and uncomplicated two vessel involvement are usually treated using a stent. Main stem stenosis, three vessel and severe two vessel involvement, particularly with reduced ventricular function, remain the domain of bypass surgery. Controlled studies show identical prognoses for patients with multiple vessel involvement for whom both treatment strategies are possible, although there is a higher reintervention rate for the stent patients. Coronary anatomy, ventricular function, as well as various patient-related factors have to be taken into account when deciding on the form of revascularisation therapy.

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Bypass; Coronary Disease; Evidence-Based Medicine; Humans; Myocardial Ischemia; Prognosis

Previously defined as the failure to achieve uniform intramyocardial reperfusion after prolonged but reversible coronary occlusion, only recently has no-reflow phenomenon been characterized as a heterogeneous clinical condition. In fact, in about half of post-infarct patients that show no-reflow after 24 hours from coronary recanalization by either thrombolysis or PTCA, no-reflow phenomenon is spontaneously reversible. Reversible no-reflow is associated with favorable left ventricular remodeling even in the absence of significant improvement in regional contractile function. Thus, it may be a clinical marker of yet unknown mechanisms, which may favorably affect myocardial response to necrosis. Based on the pathogenesis and on the time-course of no-reflow, the phenomenon may be associated with lack of patency or with loss of anatomic integrity of microvessels, with the former being potentially reversible while the latter associated with definitive tissue damage. As a consequence, possible therapeutic strategies of no-reflow have to be designed according to not only the main target [microvessel patency or integrity], but also taking into account the timing of development of the damage. This "mini review" is focused on recent advances on the pathogenesis and clinical presentation on no-reflow. These data will give the opportunity to formulate novel interpretation and classification of the phenomenon and consequently, to propose adequate therapeutic strategies.

Topics: Adenosine; Animals; Calcium Channel Blockers; Cardiovascular Agents; Coronary Circulation; Coronary Vessels; Humans; Magnetic Resonance Imaging; Microcirculation; Myocardial Ischemia; Myocardial Reperfusion Injury; Nicorandil; Potassium Channels; Randomized Controlled Trials as Topic; Vascular Patency

Topics: Cardiac Pacing, Artificial; Cardiomyopathies; Cardiovascular Agents; Coronary Angiography; Echocardiography; Heart Transplantation; Humans; Magnetic Resonance Imaging; Myocardial Ischemia; Patient Selection; Positron-Emission Tomography; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity

Topics: Arrhythmias, Cardiac; Cardiomyopathies; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Humans; Myocardial Ischemia; Risk Assessment; Ventricular Fibrillation

The heart is a pump, but also a furnace able to produce at each moment a large amount of energy and to adapt fast enough to face the changes in both fuel supply and energy demand. The pharmacological treatment of angina has been largely focused on the "pump" through hemodynamic agents aimed at decreasing cardiac effort to decrease energy demand. A new concept arose focusing the "furnace" through metabolic agents aimed at decreasing the oxygen cost of ATP production. This goal can be achieved by shifting energy production from fatty acid beta-oxidation to glucose oxidation. CPT1 inhibitors were developed to prevent the fatty acid entry into mitochondria but induced cardiac hypertrophy. Regulation of carnitine biology either by carnitine supply or by gamma-butyrobetaine hydroxylase inhibitors have led to controversial data both in pharmacological and clinical concerns. Trimetazidine and ranolazine increase the glucose/fatty acid oxidation balance and exhibit beneficial effects in animal studies as well as in clinical trials, both in monotherapy and in association with a traditional hemodynamic drug. The association of metabolic and hemodynamic agents brings additive benefits in angina, whereas associations of hemodynamics do not. The mechanism of these drugs has not been fully understood in terms of specific target. In animal studies, dietary docosahexaenoic acid allowed similar protection, through a mechanism related to membrane conformation without specific enzymic target. From the mechanistic research published in this field, enough has now been understood to foresee some future possible targets, mainly related to the cardiomyocyte fatty acid metabolism.

Topics: Acyl Coenzyme A; Animals; Cardiovascular Agents; Carnitine O-Palmitoyltransferase; Clinical Trials as Topic; Fatty Acids; Fatty Acids, Omega-3; Glucose; Humans; Mitochondria, Heart; Myocardial Ischemia; Oxidation-Reduction

Topics: Cardiovascular Agents; Clinical Trials as Topic; Enzyme Inhibitors; Humans; Myocardial Ischemia; Sodium-Calcium Exchanger

Acute myocardial ischemia may result in diverse outcomes ranging from asymptomatic episodes to frank myocardial infarction. Reperfusion therapy becomes the mainstay of treatment of patients with evolving MI and provide practical approach for salvage of ischemic myocardium. Favorable modulations of metabolic events during and after ischemia results in increased myocardial salvage in reperfused myocardium. The use of GIK showed great advantage in enhancing myocardial salvage in patients with AMI. Use of other metabolic agents show great promise in experimental studies and merits further evaluation in human trials. Metabolic modulation of ischemic myocardium continues to be a unique and untapped approach to favorably effect ischemic myocardium. Metabolic adjuncts can be employed to lessen ischemic injury and thereby enhance the salutary effects of reperfusion. The use of metabolic manipulations which enhance glycolytic pathways and inhibit potentially noxious fatty acid intermediates may also offer a noble approach for the protection of transiently ischemic myocardium in patients with coronary artery disease. And one thing is certain, that is -- agents that modify myocardial metabolism in disease states have definitely enhanced the therapeutic armamentarium to fight the problem and improve the well being of the patients.

Topics: Cardiovascular Agents; Heart; Humans; Myocardial Ischemia; Myocardium

Topics: Biomedical Research; Cardiovascular Agents; Fatty Acids, Omega-3; Humans; Myocardial Ischemia

In the UGDP study, published in the 1970s, a high incidence of cardiovascular mortality was found in patients treated with the sulfonylurea agent tolbutamide. Impaired ischaemic preconditioning is presumed to be the most important mechanism for the excess cardiovascular mortality observed. However, as tolbutamide has only a low affinity for cardiac sulfonylurea receptors, interference with ischaemic preconditioning seems unlikely to account for this excess mortality. Several smaller studies also failed to establish a definite link between sulfonylurea treatment before acute myocardial infarction and in-hospital mortality. However, when the myocardium becomes exposed to repeated or prolonged periods of ischaemia, ischaemic preconditioning may become clinically important. Myocardial ischaemia can also develop during emergency or elective angioplasty and during coronary bypass surgery. Therefore discontinuation of sulfonylurea treatment should be considered in these circumstances.

Topics: Animals; Cardiovascular Agents; Catheterization; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Ischemic Preconditioning, Myocardial; Models, Biological; Myocardial Ischemia; Randomized Controlled Trials as Topic; Sulfonylurea Compounds; Tolbutamide

According to current estimates, more than 12 million people in the United States have coronary artery disease (CAD). Slightly less than half experience angina pectoris, and more than 7 million have had a myocardial infarction. In 2000, the economic cost of CAD in this country totaled $118 billion. Given the aging of the population and the improved therapy for several other disorders, a true epidemic looms on the horizon. In this article, Dr Bales examines the long-term medical treatment of patients with known ischemic heart disease, focusing on therapies proven to alter morbidity and mortality, relieve symptoms, and modify risk factors.

Topics: Adrenergic beta-Antagonists; Angina Pectoris; Calcium Channel Blockers; Cardiovascular Agents; Chronic Disease; Humans; Myocardial Ischemia; Platelet Aggregation Inhibitors; Risk Factors

Recent cross-sectional, population-based echocardiographic studies show that about half of all patients with heart failure have preserved left ventricular systolic function (HF-PSF). Cohort studies of hospitalized patients show a smaller proportion of HF-PSF. Compared to those with reduced systolic function, patients with HF-PSF are more often female, older, less likely to have coronary artery disease, and more likely to have hypertension. Patients with HF-PSF are less symptomatic and receive different pharmacologic therapy than patients with reduced systolic function. Morbidity and mortality rates in patients with HF-PSF are high but not quite as high as in patients with reduced systolic function. Though much has recently been learned about the syndrome of HF-PSF, many questions remain to be answered, not least how it should be treated.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Comorbidity; Female; Heart Failure; Hospitalization; Humans; Hypertension; Male; Middle Aged; Myocardial Ischemia; Prognosis; Quality of Life; Ventricular Function, Left

Antianginal drugs that exert their anti-ischaemic effects primarily by altering myocardial metabolism have recently attracted attention. They have the potential to relieve symptoms in patients with refractory angina who are already on "optimal" medical therapy and have disease that is not amenable to revascularisation, making these drugs an attractive addition to therapy, particularly for the elderly population. In some cases, they may even be used as first-line treatment. These drugs increase glucose metabolism at the expense of free-fatty-acid metabolism, enhancing oxygen efficiency during myocardial ischaemia. Whilst they have been demonstrated to reduce ischaemia in several clinical trials, their use remains limited. This review aims to draw attention to these "metabolic" antianginal drugs while surveying the evidence supporting their use and mode of action. Four metabolic antianginal drugs are reviewed: perhexiline, trimetazidine, ranolazine, and etomoxir. We also discuss the metabolic actions of glucose-insulin-potassium and beta-blockers and describe myocardial metabolism during normal and ischaemic conditions. The potential of these metabolic agents may extend beyond the treatment of ischaemia secondary to coronary artery disease. They offer significant promise for the treatment of symptoms occurring due to inoperable aortic stenosis, hypertrophic cardiomyopathy, and chronic heart failure.

Topics: Acetanilides; Adrenergic beta-Antagonists; Angina Pectoris; Cardiovascular Agents; Drug Therapy, Combination; Enzyme Inhibitors; Epoxy Compounds; Glucose; Humans; Hypoglycemic Agents; Insulin; Myocardial Ischemia; Myocardium; Perhexiline; Piperazines; Potassium; Ranolazine; Trimetazidine

The authors in the article described biochemical mechanisms of Mildronat. The main mechanism of Mildronat activity is based on decreasing carnitine level in the organism, which leads to hampering oxidation of fatty acids. Mildronat is believed keeps on training myocardium pharmacologically even without physical activity by adapting cells to decreasing fat acids inflow and activating glucose oxidations. Under ischemic condition to obtain energy, cells use intensively glucose oxidation. Clinical studies have reliably showed Mildronat to have positive effect in treating patients with cardiovascular and ischemic cerebral diseases as well as for enhancing physical and mental efficiency.

Topics: Animals; Cardiovascular Agents; Carnitine; Clinical Trials as Topic; Humans; Methylhydrazines; Myocardial Ischemia; Myocardium; Oxidative Stress; Treatment Outcome

Topics: Alcohol Drinking; Antihypertensive Agents; Cardiovascular Agents; Comorbidity; Diabetes Mellitus; Diet, Reducing; Diet, Sodium-Restricted; Heart Failure; Humans; Hypertension; Kidney Diseases; Life Style; Motor Activity; Myocardial Ischemia; Obesity; Practice Guidelines as Topic; Weight Loss

The number of patients with coronary artery disease and its risk factors is increasing in Western nations. New treatments for these patients may soon include a class of agents known as the metabolic modulators. This group of agents consists of the partial fatty acid oxidation inhibitors trimetazidine and ranolazine, as well as dichloroacetate, which promotes carbohydrate utilization. Metabolic modulators also include the nutriceuticals L-carnitine and D-ribose. The available evidence regarding the benefits of each of these five agents is reviewed.

Topics: Acetanilides; Cardiovascular Agents; Carnitine; Dichloroacetic Acid; Energy Metabolism; Humans; Myocardial Ischemia; Oxidation-Reduction; Piperazines; Ranolazine; Ribose; Trimetazidine

Apoptosis continues to be a controversial concept and subject of debate among scientists regarding its value as the basis for new therapeutic strategies. Today, it is widely accepted that the death of cardiac myocytes under a variety of conditions appears to be apoptotic based on a variety of criteria. However, the significance of these observations and how the insights into apoptotic molecular pathways may provide novel therapeutic targets remains to be determined. It is important to reconsider the pertinent underlying mechanisms of apoptosis regulation, and how these molecular pathways may be viewed in the functioning, intact heart. This knowledge can be applied in pursuit of practical goals in a search for new ways to prevent myocardial damage following such injuries as ischaemia/reperfusion or exposure to cardiotoxic drugs. Although recent literature contains reports of positive findings, there has not yet been a rigorous application of the model of apoptosis in the myocardium, and the potential for development of new therapeutic strategies is not yet understood.

Topics: Animals; Apoptosis; Biological Evolution; Cardiovascular Agents; Cell Differentiation; Cysteine Proteinase Inhibitors; Drug Design; Endothelial Cells; Humans; Lysophospholipids; Myocardial Ischemia; Myocarditis; Myocardium; Myocytes, Cardiac; Necrosis; Rats; Signal Transduction

In recent years, basic research has enabled a better understanding of the molecular and cellular basis of myocardial ischemia. In this context, cardiac mitochondria have been shown to perform an important role, being essential to energy production and ionic homeostasis, and thus controlling cardioprotection and cell death. Knowledge of these facts has led to the development of new therapeutic strategies for myocardial ischemia, aiming to modify its biochemical pathways and to preserve mitochondrial function. It has also led to a better understanding of the cellular and subcellular effects of classical anti-ischemic drugs, revealing that most of them also have a direct impact on cardiac mitochondrial function. This article summarizes what is currently known regarding the pharmacological modulation of mitochondrial function during ischemia and reperfusion and how it can induce cardioprotection in coronary artery disease patients.

Topics: Animals; Cardiovascular Agents; Humans; Mitochondria, Heart; Myocardial Ischemia; Myocardial Reperfusion

Ischemic heart disease (IHD) is a kind of severe cardiovascular disease. It has become one of the main reasons resulting in people's death. So it is very pressing to explore some active substances with anti-myocardial ischemia physiological activity. It is important to develop some safe and effective drugs. In this paper we review the advance in study on the source, chemical ingredient and pharmacological action of the anti-myocardial ischemia of thirty kinds of nature products.

Topics: Animals; Cardiovascular Agents; Drugs, Chinese Herbal; Humans; Myocardial Ischemia; Plants, Medicinal

While attention has historically focused on mitochondria as the primary source of ROS in myocardial ischemia/reperfusion injury, recent evidence has implicated cytochrome P450 monooxygenases (CYPs) as a significant factor. CYPs represent a large family of enzymes that catalyze the oxidation of endogenous and exogenous compounds. They catalyze arachidonic acid oxidation to a variety of biologically active eicosanoids that regulate ion channels and protein kinases, with effects on vasomotor tone and cardiac inotropy. They also represent a significant source of reactive oxygen species that may target cellular homeostatic mechanisms and mitochondria. In this review, we will consider the contribution of cytochrome P450 enzymes to reperfusion injury and will speculate on whether the mechanism of injury is due to CYP-mediated ROS production or arachidonic acid metabolites.

Topics: Animals; Apoptosis; Arachidonic Acid; Cardiovascular Agents; Cytochrome P-450 Enzyme System; Eicosanoids; Enzyme Activation; Humans; Isoenzymes; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Reactive Oxygen Species

Topics: Adolescent; Adult; Aged; Antihypertensive Agents; Arrhythmias, Cardiac; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Calcium Channel Blockers; Cardiovascular Agents; Catecholamines; Chronotherapy; Circadian Rhythm; Clinical Trials as Topic; Cross-Over Studies; Delayed-Action Preparations; Diltiazem; Double-Blind Method; Electrocardiography, Ambulatory; Hemodynamics; Humans; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Myocardial Ischemia; Sleep; Stroke; Verapamil

Thiazide diuretics, b-blockers, calcium channel blockers, and angiotensin converting enzyme (ACE) inhibitors are all superior to placebo for the primary prevention of coronary events in patients with hypertension. Recent studies have shown that ACE inhibitors are better than other antihypertensive agents in lowering overall cardiovascular morbidity and mortality, especially stroke. Blood pressure should be aggressively lowered (to < 140/90 mm Hg), especially in diabetic patients (to < 130/80 mm Hg), but care should be exercised in lowering the diastolic blood pressure below 65 mm Hg in patients with significant occlusive coronary artery disease. Hypertension in patients with stable angina should be treated with a b-blocker (alternatively a calcium channel blocker) together with an ACE inhibitor. Patients with hypertension and acute coronary syndrome (unstable angina or myocardial infarction) should be treated with a b-blocker, and with an ACE inhibitor if there is left ventricular dysfunction. A thiazide diuretic and/or a dihydropyridine calcium channel blocker could be added for blood pressure control. Calcium channel blockers should be avoided if there is significant left ventricular dysfunction.

Topics: Angina, Unstable; Blood Pressure; Cardiovascular Agents; Clinical Trials as Topic; Humans; Hypertension; Myocardial Infarction; Myocardial Ischemia

Although the past number of years have seen a substantial improvement in the therapeutic approaches for the treatment of heart failure, mortality rates continue to be high. Moreover, the incidence of heart failure is expanding rapidly. Sodium-hydrogen exchange (NHE) is a key target for the treatment of heart failure. NHE is a major mechanism for intracellular pH regulation in most cell types, including the cardiac cell. Seven isoforms of NHE have been identified so far although cardiac cells possess primarily the ubiquitous NHE-1 subtype. NHE-1 is a major contributor to ischaemic and reperfusion injury and NHE-1 inhibitors exert marked cardioprotective effects, particularly when administered before ischaemia, findings which have now been extended to clinical trials. It is emerging that NHE-1 also contributes to chronic maladaptive myocardial responses to injury (myocardial remodelling) and may contribute to the development of heart failure. Experimental studies using both in vitro approaches as well as animal models of heart failure have consistently demonstrated a beneficial effect of NHE-1 inhibitors in terms of inhibition of hypertrophy in response to various stimuli as well as inhibiting heart failure after coronary artery ligation. These effects occurred independently of any infarct size reducing effects of NHE-1 inhibitors or on any direct effects on afterload thus indicating a direct effect on the myocardial remodelling process. In fact, it appears that NHE-1 may represent a common downstream mediator for various hypertropic factors such as angiotensin II, endothelin-1 and beta(1) adrenergic receptor activation. NHE-1 inhibition, therefore, represents a potentially effective new therapeutic approach for the treatment of heart failure.

Topics: Animals; Cardiomegaly; Cardiovascular Agents; Drug Design; Drug Evaluation, Preclinical; Gene Expression Regulation; Heart Failure; Humans; Hypertrophy, Left Ventricular; Ion Transport; Myocardial Ischemia; Myocardial Reperfusion Injury; Rats; Sodium; Sodium-Hydrogen Exchangers; Ventricular Remodeling

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Bypass; Dioxolanes; Feeding Behavior; Heptanoic Acids; Humans; Life Style; Myocardial Infarction; Myocardial Ischemia; Randomized Controlled Trials as Topic; Recurrence; Risk Factors; Stents; Survival Rate; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Bypass; Dioxolanes; Feeding Behavior; Heptanoic Acids; Humans; Life Style; Myocardial Infarction; Myocardial Ischemia; Recurrence; Risk Factors; Stents

Topics: Angioplasty, Balloon, Coronary; Cardiac Catheterization; Cardiovascular Agents; Coronary Artery Bypass; Diagnostic Imaging; Heart Function Tests; Humans; Myocardial Ischemia; Practice Guidelines as Topic; Prognosis; Tissue Survival

This article reviews the fundamentals of myocardial energy metabolism and selectively outlines the use of several metabolically active drug therapies in the treatment of ischemic heart disease. These drugs - ranolazine, trimetazidine, dichloroacetate (DCA), glucose-insulin-potassium (GIK) solutions, and L-carnitine - have mechanisms of action distinct from traditional anti-ischemic drugs. These agents work by shifting myocardial energy metabolism away from fatty acids toward glucose as a source of fuel. Because these agents are well tolerated and do not affect heart rate or blood pressure, they conceivably could supplement traditional anti-ischemic drug therapy with little risk. The background, rationale for use, and published literature on each agent is reviewed, and the outcomes of pertinent clinical trials are discussed. In the case of ranolazine, data suggest benefit in the treatment of stable angina pectoris, particularly with sustained release formulations. Trimetazidine appears to have similar physiologic effects to ranolazine, and it is effective as monotherapy and as additive therapy in patients with chronic ischemic heart disease. DCA improves acidosis in critically ill patients and, likewise, improves myocardial hemodynamics in those with chronic coronary artery disease and congestive heart failure; however, its metabolism is variable and clinical data on its use in chronic ischemic heart disease are limited. GIK solutions have been shown to be beneficial in animal and human models of ischemia and acute myocardial infarction, and they offer an inexpensive means by which to improve the oxidation of glucose in the heart. Lastly, a large body of literature suggests a benefit with L-carnitine in a number of cardiovascular illnesses, including ischemic heart disease. Clinical trial data in acute myocardial infarction are promising and have prompted the initiation of a large-scale mortality trial.

Topics: Acetanilides; Animals; Cardiovascular Agents; Carnitine; Clinical Trials as Topic; Dichloroacetic Acid; Energy Metabolism; Fatty Acids; Glucose; Humans; Insulin; Myocardial Ischemia; Myocardium; Piperazines; Potassium; Ranolazine; Trimetazidine

Carvedilol is a unique cardiovascular drug of multifaceted therapeutic potential. Its major molecular targets recognized to date are membrane adrenoceptors (beta 1, beta 2, and alpha 1), reactive oxygen species, and ion channels (K+ and Ca2+). Carvedilol provides prominent hemodynamic benefits mainly through a balanced adrenoceptor blockade, which causes a reduction in cardiac work in association with peripheral vasodilation. This drug assures remarkable cardiovascular protection through its antiproliferative/atherogenic, antiischemic, antihypertrophic, and antiarrhythmic actions. These actions are a consequence of its potent antioxidant effects, amelioration of glucose/lipid metabolism, modulation of neurohumoral factors, and modulation of cardiac electrophysiologic properties. The usefulness of carvedilol in the treatment of hypertension, ischemic heart disease, and congestive heart failure is based on a combination of hemodynamic benefits and cardiovascular protection.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Animals; Antihypertensive Agents; Antioxidants; Blood Glucose; Carbazoles; Cardiovascular Agents; Cardiovascular System; Carvedilol; Heart Conduction System; Heart Failure; Humans; Hypertension; Lipids; Myocardial Ischemia; Neurotransmitter Agents; Propanolamines

Topics: Adenosine; Cardiovascular Agents; Contrast Media; Coronary Artery Disease; Dipyridamole; Dobutamine; Exercise Test; Humans; Image Enhancement; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Monitoring, Physiologic; Myocardial Ischemia

The cardiac mechano- and chemoreceptors are broadly distributed in the myocardium and coronary vessels. A portion of these receptors extends over the epicardium and pericardium and therefore can be excited by mechanical or chemical stimuli directly applied to the surface of the heart. Excitation of epicardial receptors by topical application of chemical compounds elicits a variety of reflex cardiovascular responses, without the vascular or systemic effects of the drug administered systemically. A considerable number of studies has used the epicardial sensory field as a tool to delineate the functional characteristics of the cardiac afferent neurones in normal as well as in pathological conditions. In this review we analyze the cardiovascular reflex responses induced by epicardial application of a variety of substances like bradykinin, nicotine, muscarine, isoprenaline, adenosine, potassium chloride, capsaicin, prostaglandins or substance P in physiological models and also in models with acute myocardial ischemia or heart failure. The data highlight the contribution of the epicardial sensory neurites to the overall control of the cardiovascular system and, on the other hand, strengthen the need for further investigations directed to better elucidate the reflex cardiovascular responses that may develop in patients with pericardial abnormalities.

Topics: Animals; Cardiovascular Agents; Cardiovascular Physiological Phenomena; Chemoreceptor Cells; Heart; Humans; Mechanoreceptors; Myocardial Ischemia; Reflex

ATP-sensitive potassium channels (K(ATP)) have been thought to be a mediator of cardioprotection for the last ten years. Significant progress has been made in learning the pharmacology of this channel as well as its molecular regulation with regard to cardioprotection. K(ATP)openers as a class protect ischemic/reperfused myocardium and appear to do so by conservation of energy. The reduced rate of ATP hydrolysis during ischemia exerted by these openers is not due to a cardioplegic effect and is independent of action potential shortening. Compounds have been synthesized which retain the cardioprotective effects of first generation K(ATP)openers, but are devoid of vasodilator and cardiac sarcolemmal potassium outward currents. These results suggest receptor or channel subtypes. Recent pharmacologic and molecular biology studies suggest the activation of mitochondrial K(ATP)as the relevant cardioprotective site. Implications of these results for future drug discovery and preconditioning are discussed.

Topics: Adenosine Triphosphate; Animals; Cardiovascular Agents; Cell Membrane; Humans; Ischemic Preconditioning, Myocardial; Mitochondria, Heart; Myocardial Ischemia; Potassium Channels; Sarcolemma

Perioperative cardiac morbidity and mortality are a major health care challenge with important individual as well as economic aspects. Up to 30% of all perioperative complications and up to 50% of all postoperative deaths are related to cardiac causes. Perioperative myocardial ischemia, which occurs in more than 40% of patients with or at risk for coronary artery disease and undergoing noncardiac surgery, represents a dynamic predictor of postoperative cardiac complications. Long-duration myocardial ischemia and ischemic episodes associated with myocardial cell damage are particularly of prognostic relevance. In patients suffering from this type of ischemia, the incidence of adverse cardiac outcome is increased up to 20-fold. Reducing the incidence of perioperative myocardial ischemia is associated with a decrease in adverse cardiac outcome. Important issues related to perioperative myocardial ischemia are hematocrit level, body temperature, and hemodynamic variables. In contrast, the choice of anesthetic agents and techniques appears to be less important. Perioperative administration of anti-ischemic drugs in patients at risk, however, leads to a further decrease in the incidence of myocardial ischemia and to an improvement in patient outcome. Recent studies suggest that alpha 2-agonists and particularly beta-adrenoreceptor blocking agents are effective anti-ischemic drugs in the perioperative setting. Perioperative administration of beta-adrenoreceptor blocking agents in coronary risk patients undergoing noncardiac surgery is associated with a reduced rate of postoperative cardiac complications and an improvement in long-term outcome. This is particularly relevant in high risk patients with preoperative stress-induced ischemic episodes. In clinical practice, therefore, chronically administered anti-ischemic drugs should also be administered on the day of surgery and during the postoperative period. In untreated patients with or at risk for coronary artery disease and who have to undergo urgent surgical procedures without the opportunity of preoperative anti-ischemic intervention, perioperative administration of beta-adrenoreceptor blocking agents is mandatory.

Topics: Cardiovascular Agents; Humans; Intraoperative Complications; Myocardial Ischemia; Surgical Procedures, Operative

Topics: Blood Pressure; Cardiovascular Agents; Chronobiology Phenomena; Chronotherapy; Heart Rate; Humans; Hypertension; Myocardial Ischemia; Treatment Outcome

The comparative study of ion homeostatic regulation in the cardiomyocytes in health and in experimental hypoxia showed that the elevated diastolic concentration of free ions of sodium ([Na+]in and calcium ([Ca2+]cyt) in the cardiomyocytic cytoplasm, the lower resting potential of the cell plasma membrane (delta phi n) are major arrhythmogenic agents. The decreased (delta phi n) is mainly defined by lower Na+/K(+)-ATPase activity due to insufficient energy production. The activation of Na+/H(+)-antiport underlies the elevation of [Na+]cyt. The mechanisms responsible for increased [Ca2+]cyt are increased Na/Ca exchange and inhibited Ca-ATPases in the sarcoplasmic reticulum. A test system was developed to choose and study the antiarrhythmic activity of new agents in in vitro experiments by using isolated cardiomyocytes. The screening scheme proposed involves a consecutive evaluation of the effects of chemicals on the changes occurring in the (delta phi n) of cellular Na and Ca exchange. A concept describing the molecular and cellular factors predisposing to cardiac arrhythmias and ischemic alteration is formulated; possible points of application of the cardioprotective and antiarrhythmic agents were identified.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Drug Combinations; Humans; Ion Pumps; Membrane Potentials; Myocardial Ischemia; Myocardium

Nicorandil, a potassium-channel activator used for the long-term treatment of ischemic heart disease, has been recently implicated as having a drug side effect of recurrent aphthous stomatitis. Three patients are reported with drug-induced aphthouslike ulceration secondary to nicorandil.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Humans; Male; Myocardial Ischemia; Nicorandil; Oral Ulcer; Potassium Channels

This review discusses the circadian phase dependency in the anti-anginal effects and in the pharmacokinetics of drugs used in the treatment of coronary heart diseased patients. beta-receptor blocking agents seem mainly to reduce ischaemic events during daytime hours and are of therapeutic value in the morning hours which are the hours of high cardiovascular risk. Calcium channel blockers seem to be less effective in reducing ischaemic event during the night and early morning. However, the galenic formulation and the type of calcium channel blocker may play an important role. Whereas the effects of the anti-ischaemic properties of oral nitrates are well established, their influence of the circadian organization of cardiovascular events needs to be clarified. Only limited data are available concerning the circadian phase dependency in the dose-response relationship of anti-anginal drugs. Such data would be valuable for a better understanding of the need of a time-specified drug treatment which is based on the circadian phase dependency of cardiovascular events such as coronary infarction and angina pectoris attacks.

Topics: Acute Disease; Adrenergic alpha-Antagonists; Calcium Channel Blockers; Cardiovascular Agents; Chronotherapy; Coronary Disease; Humans; Myocardial Ischemia; Nitrates; Syndrome

Topics: Anemia; Cardiovascular Agents; Combined Modality Therapy; Drug Therapy, Combination; Humans; Hypertension; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Myocardial Ischemia; Renal Dialysis

A rational approach to the treatment of chronic myocardial ischemia requires an appreciation of the pathophysiology of coronary artery disease and the treatment options available. Any factor that causes an imbalance between myocardial oxygen supply and demand can provoke ischemia. Myocardial oxygen requirements rise with increases in heart rate, contractility, or left ventricular wall stress. Myocardial oxygen supply is determined by coronary artery flow and myocardial oxygen extraction. Anti-anginal medications are the mainstay of anti-ischemic management and act to correct the balance between myocardial supply and demand by increasing coronary blood flow, reducing myocardial oxygen requirements, or both. These medications include nitrates (which act principally by venous vasodilation, but also probably by coronary dilation), beta-blockers (which act mainly by reducing heart rate and cardiac contractility), and calcium channel blockers (which act principally by arterial and coronary vasodilation). The choice of therapy and its effectiveness depend on the underlying cause of ischemia. The complimentary mechanisms of action of these drug classes suggest that their use in combination may result in a greater reduction in myocardial oxygen demand than that achieved with monotherapy. In addition, the pharmacological actions of some of these drugs may serve to offset the undesirable side effects associated with others, for example, the reflex tachycardia produced by some calcium channel blockers may be offset by beta-blocker therapy. Finally, aspirin and lipid-lowering drugs and the potential role for anti-oxidants must also be considered in combination therapy. Invasive techniques for myocardial ischemic management, such as coronary artery bypass and coronary angioplasty, improve myocardial oxygen supply by relieving or circumventing the atherosclerotic obstruction responsible for ischemia. Surgery is the preferred technique in patients with certain medical conditions, for example, those with triple-vessel disease, but is not recommended in patients with mild angina unless left main artery disease is present.

Topics: Animals; Cardiovascular Agents; Chronic Disease; Coronary Disease; Humans; Myocardial Ischemia

Clinical trials in heart failure (HF) tend to randomize patients according to demographic characteristics and severity of left ventricular dysfunction, without taking account of the precise diagnosis. This article reviews results from recent trials suggesting that the etiology of HF, and particularly whether it is ischemic or nonischemic, may influence the long-term prognosis and the response to treatment. Some studies, but not all, suggest that nonischemic HF has a better prognosis than ischemic HF. The data on the benefits of angiotensin-converting enzyme inhibitors in ischemic versus nonischemic HF are conflicting. Carvedilol, and recently, bisoprolol have been shown to reduce mortality in ischemic and nonischemic HF, whereas metoprolol has, to date, improved prognosis only in dilated cardiomyopathy. Better responses to digoxin, amlodipine and amiodarone have been reported in non-ischemic HF. There is at present no clear explanation for the apparent therapeutic differences between ischemic and nonischemic HF. Absence of a rigorous definition of "nonischemic HF" in many studies makes interpretation of the results difficult. Further studies to clarify the effects of etiology of HF on the response to treatment could be particularly important for preventing progression to more advanced stages, in which any type of drug therapy may have limited value in prolonging survival. An individualized therapeutic approach, based on etiology of HF and possibly other factors such as plasma drug levels or the levels of neurohormones, could result in major progress in treating HF patients.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiac Glycosides; Cardiomyopathy, Dilated; Cardiovascular Agents; Diagnosis, Differential; Diuretics; Drug Therapy, Combination; Heart Failure; Humans; Myocardial Ischemia; Prognosis; Randomized Controlled Trials as Topic

Primary care physicians have an important role in timely diagnosis and appropriate treatment of gravid patients with cardiac disorders. Health of the mother and child can be optimized with thorough understanding of the pathophysiology of cardiac disorders during pregnancy, especially those with potentially serious effects, such as peripartum cardiomyopathy and acute myocardial infarction. Mitral stenosis often manifests for the first time during pregnancy. Mitral valve prolapse is usually benign but in some cases necessitates antibiotic prophylaxis for delivery. Pregnancy in women with prosthetic cardiac valves may expose mother and child to risks that can be minimized with appropriate safeguards.

Topics: Cardiomyopathies; Cardiovascular Agents; Contraindications; Female; Heart Diseases; Humans; Mitral Valve Stenosis; Myocardial Ischemia; Pregnancy; Pregnancy Complications, Cardiovascular

Current management of patients after an acute myocardial infarction (AMI) reflects a variety of approaches ranging from conservative to aggressive. Although each method is appropriate in certain subgroups, their application frequently lacks a scientific basis. Current, clinically relevant, evidence-based practice guidelines are needed for secondary prevention for survivors after an AMI. To meet this need, the California Cardiology Working Group was assembled to evaluate the available data from clinical trials and other published studies and develop evidence-based, cost-effective guidelines for clinicians to use as a basis for patient management after an AMI. The group consisted of 18 members, including cardiologists from academic institutions and physicians working in cardiac intensive care, private practices, and managed care settings, representing a broad spectrum of expertise pertaining to patients who have had an AMI. The members had expertise in cardiac intensive care, interventional cardiology, nuclear cardiology, lipid disorders, echocardiography, and cardiac rehabilitation. The intended audience for these practice guidelines includes all physicians who treat survivors of MI. A literature review of all relevant clinical trials and other published data about the natural history after AMI and the effects of current therapeutic modalities are discussed herein. Case histories served as models for application of the literature-based data. The recommendations for management were reached by consensus vote based on the scientific evidence. When more than 1 management option applied, this was recognized in the recommendations. The recommendations accompany the text.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Cost-Benefit Analysis; Evidence-Based Medicine; Exercise; Humans; Hyperlipidemias; Hypertension; Myocardial Infarction; Myocardial Ischemia; Prognosis; Risk; Risk Factors; Smoking; Ventricular Function, Left

The term unstable angina should only be used to describe patients whose immediate prognosis is uncertain and the nature of the unstable disease may vary on a patient to patient basis, making broad categorization of such patients inappropriate. Unstable angina may be caused by extracardiac factors, such as uncontrolled hypertension and tachycardia, disruption of an atheromatous plaque, dynamic or intermittent coronary artery thrombosis, haemorrhagic dissection into an atheromatous plaque, epicardial coronary spasm or progression of atherosclerosis as a result of plaque healing. Control of symptoms using medical therapy with a combination of nitrates, beta-blockers and calcium antagonists is usually quite successful. In the absence of contra-indications, intravenous heparin, and possibly anti-platelet agents, should also be used in the acute phase of treatment. In addition, one aspirin a day is indicated unless there are definite contra-indications. If symptoms are relieved, evaluation and management should proceed as with chronic stable angina. Identification of patients with a poor prognosis should be the main indication for urgent revascularization. One of the best predictors of a poor prognosis in unstable disease is persistent pain despite optimum therapy. Urgent surgery should be considered in any patient with multivessel coronary artery stenosis who has evidence of persistent myocardial ischaemia, despite adequate medical therapy.

Topics: Angina, Unstable; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Bypass; Humans; Myocardial Ischemia; Randomized Controlled Trials as Topic; Survival Rate; Treatment Outcome

Despite the remarkable advances in cardiovascular therapeutics over the past four decades, little impact has been made on either the incidence or mortality rate of congestive heart failure and it remains a major clinical and public health problem. Recent practice audits have suggested that proven efficacious therapies are not maximally applied in patients with this condition. An approach to the patient with congestive heart failure is presented, emphasizing the two distinct syndromes of systolic dysfunction and diastolic dysfunction. Treatment recommendations are derived from consideration of the underlying pathophysiology and the evidence from randomised clinical trials.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Clinical Trials as Topic; Diet, Sodium-Restricted; Diuretics; Drinking; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Prevalence; Risk Factors; Severity of Illness Index; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right; Warfarin

Topics: Adenosine; Cardiovascular Agents; Echocardiography; Exercise Test; Humans; Myocardial Ischemia; Vasodilator Agents

The state of art in the treatment of silent myocardial ischemia is reviewed in such a way as to provide with the cardiologist information for the correct decision to be made in patients with ischemia, but without clinical symptoms of angina and its equivalents. Previewed-required, the concept, the classification and the diagnostic methods were reviewed. The prognosis, pharmacological treatment, intervention procedures and their results on the natural history of the disease are emphasised. It is recommended that the treatment of silent ischemia be done, at first, with primary and secondary prevention, and with pharmacological therapy. It is assumed that with the reduction of general ischemic episodes, survival can be individualized. New techniques have been introduced that modify the results in both the short and long term of these procedures.

Topics: Cardiovascular Agents; Humans; Myocardial Ischemia; Myocardial Revascularization; Prognosis

One of the most difficult problems related to coronary artery disease is the detection and eventual treatment of silent myocardial ischemia (SMI). After defining the concept of SMI and total ischemia burden, the author approaches the pathophysiology of myocardial ischemia and focuses on the ischemic cascade. Concerning the detection of SMI the importance of exercise testing and Holter ECG is stressed. Following the classification of SMI proposed by P. F. Cohn, the author analyzes SMI type III with particular interest. He refers the prevalence of SMI in patients suffering from chronic stable angina, and focuses on the prognostic importance of SMI. Afterwards, the problem of treatment and prognostic implications is approached. The paper ends with mention of the results of the most important clinical trials in this field: CASIS, CAPE, TIBBS, ASIST, ACIP, TIBET.

Topics: Angina Pectoris; Cardiovascular Agents; Clinical Trials as Topic; Humans; Myocardial Ischemia; Prevalence; Prognosis

Topics: Adenosine; Alkaloids; Animals; Benzophenanthridines; Cardiovascular Agents; Drug Therapy, Combination; Enzyme Inhibitors; Humans; Ischemic Preconditioning, Myocardial; Myocardial Ischemia; Phenanthridines; Protein Kinase C; Rabbits; Rats

The predictive value of a screening test depends on its accuracy and the pretest likelihood of disease (i.e, prevalence of the disease in the population). In ischemic heart disease, there are no absolute indications for exercise electrocardiographic testing in asymptomatic patients. However, it is the major noninvasive test for coronary artery disease (CAD). We prefer to use exercise testing whenever possible, because it provides physiologic data that may indicate prognosis and aid in decision making regarding medical treatment. In several situations, exercise assessment combined with radionuclide angiography or echocardiography is indicated for evaluation of patients with CAD. In certain groups of patients, pharmacologic stress testing is preferred. The two methods used most often are dipyridamole administration followed by thallium perfusion imaging and dobutamine administration followed by echocardiography. They have similar sensitivity, specificity, and diagnostic accuracy for CAD and CAD events. Coronary angiography, although invasive, remains the "gold standard" for assessment of CAD and its severity. It is most useful in combination with results of exercise testing. Beta-adrenergic blockers, calcium channel blockers, and nitrates have specific uses in CAD and should be chosen on the basis of their pharmacologic properties. Further details regarding non-pharmacologic and pharmacologic treatment and revascularization strategies in patients with CAD are discussed elsewhere in this symposium.

Topics: Cardiovascular Agents; Echocardiography; Exercise Test; Humans; Myocardial Ischemia; Radionuclide Angiography

To help resolve abnormalities in cardiovascular function, many different types of drugs have been developed. Only recently, however, has there been increased emphasis on determining flow these agents decrease morbidity and mortality. In some cases, standard drug therapy has been challenged somewhat by newer drugs or new applications of existing drugs that seem to provide better outcomes in terms of disease progression and survival. The purpose of this article is to provide an update on contemporary pharmacologic management of three common conditions: hypertension, congestive heart failure, and myocardial ischemia/infarction. Physical therapists should be aware of the rationale for using specific drugs in each condition and that these medications can have positive therapeutic effects and adverse side effects that can influence the patient's response to physical therapy.

Topics: Cardiovascular Agents; Heart Failure; Humans; Hypertension; Morbidity; Myocardial Ischemia; Physical Therapy Modalities; Survival Rate; Treatment Outcome

Ischemic heart disease and contributing risk factors such as the hyperlipoproteinemic states affect a great percentage of the general population. Because these disease processes can effectively place patients at risk for a life-threatening event, every health care provider must be knowledgeable, disciplined to take a thorough medical history, and prepared for emergency situations that may arise in the clinical practice of dentistry. A proactive approach to identification of risk factors and to primary prevention of ischemic heart disease not only helps to lengthen and improve the quality of patient's lives, but also ensures that necessary modifications of treatment reflect each patient's medical and pharmacologic status.

Topics: Cardiovascular Agents; Dental Care for Chronically Ill; Emergencies; Humans; Hyperlipoproteinemias; Hypolipidemic Agents; Medical History Taking; Myocardial Ischemia; Quality of Life; Risk Factors

1. Myocardial ischaemia and infarction activate vagal and sympathetic sensory endings in the ischaemic myocardium, resulting in powerful reflex effects. The vagal afferents are either mechano- or chemosensitive, whereas sympathetic afferents may be mechano-, chemosensitive or both. 2. Activation of vagal afferents results in sympathoinhibitory, cardioinhibitory, vasodepressor responses. Cardiac sympathetic afferents activated during myocardial ischaemia mediate sympathoexcitatory, vasoconstrictor cardioaccelerator responses. 3. The focus of the present review is on the activation of sympathetic afferents by myocardial ischaemia and on the resulting reflex responses that they mediate. 4. These endings are more likely to be activated as the degree of ischaemia progresses from subendocardial towards transmural. They are evenly distributed between the anterior and inferoposterior wall. Although it has been suggested that these endings are activated by bradykinin, recent evidence indicates that they are activated by adenosine released from the ischaemic myocardium. Results from our laboratory indicate that this effect is due to the activation of adenosine A1, but not adenosine A2 receptors. 5. Activation of ventricular vagal and sympathetic afferent fibres during myocardial ischaemia in humans is responsible for the autonomic changes observed and, in the case of the sympathetic afferents, for the sensation of angina pectoris.

Topics: Adenosine; Animals; Cardiovascular Agents; Heart Conduction System; Humans; Myocardial Ischemia; Neurons, Afferent; Reflex; Sympathetic Nervous System; Vagus Nerve

Topics: Antidepressive Agents; Cardiovascular Agents; Depression; Humans; Myocardial Infarction; Myocardial Ischemia

Angina pectoris and asymptomatic myocardial ischemia are part of the spectrum of coronary heart disease. Not the presence or absence of angina determines the future of the patient, but repeated ischemia and the progression of the coronaropathy. This progression is neither linear with time, nor is the moment of plaque rupture foreseeable. Silent myocardial infarctions increase with age and are very frequent in diabetics. In patients without neuropathy but with asymptomatic myocardial ischemia the central pain threshold is higher than in patients with angina pectoris. The best noninvasive test for the detection, localization and estimation of extension of myocardial ischemia, be it pain-free or symptomatic, is 201-thallium scintigraphy, combined with the exercise ECG. The fight against all amendable cardiovascular risk factors and pharmacotherapy are the first steps, if asymptomatic myocardial ischemia is suspected. Augmented dyspnea on effort and rhythm disturbances are indicators of advanced multivessel heart disease. Under these circumstances coronary angiography is indicated, and further treatment should follow the generally accepted rules such as for patients with angina pectoris.

Topics: Aging; Angina Pectoris; Cardiovascular Agents; Coronary Disease; Diabetes Complications; Exercise Test; Humans; Myocardial Ischemia; Prognosis; Thallium Radioisotopes

One of every four persons in the Western industrialised nations has cardiovascular disease. The perioperative setting in those patients is associated with the risk of myocardial ischaemia (PMI) and myocardial infarction, and also with the risk of perioperative stroke and dysfunction of the central nervous system (CNS). Perioperative cardiovascular morbidity represents a major healthcare challenge. The relevance of PMI is well documented. It has been demonstrated in early trials that both myocardial ischaemia and infarction are preventable in high-risk patients undergoing surgery, and that therapeutic agents such as adenosine-related agents, alpha 2-agonists, and other stress modulators can be safely administered to these patients. Regarding perioperative stroke, approximately 3 to 7% of patients undergoing cardiac surgery suffer stroke, with an additional 30% or more suffering in-hospital CNS dysfunction, and 10% suffering moderately severe long-term CNS dysfunction. Few data are available for noncardiac surgery. The number of outcome studies addressing prophylactic or therapeutic options in these patients is quite limited. In fact, only one recent study has established that perioperative stroke is preventable with the use of an adenosine-regulating agent. Thus, it appears that it may be possible to prevent stroke, even though these results require confirmation. Because of the aging of our population, and the medical, financial and social impact of cardiovascular disease, the development of anti-ischaemic therapy, particularly in the surgical patient, will be a critical area of medical research for the next several decades.

Topics: Anesthesia, General; Brain Damage, Chronic; Cardiovascular Agents; Cardiovascular Diseases; Cerebrovascular Disorders; Humans; Intraoperative Complications; Myocardial Infarction; Myocardial Ischemia; Postoperative Complications; Premedication; Risk Factors

The pharmacotherapy of ischemic heart disease has evolved at a rapid pace during the past several decades. Drug therapy is prescribed for ischemic heart disease to either increase myocardial oxygen supply, decrease myocardial oxygen demand, or both. Although the types and number of drugs to treat ischemic heart disease are increasing and will continue to do so, there are still several major categories of pharmacologic agents that are essential in managing ischemic heart disease. The major drug categories covered are antiplatelet agents, anticoagulants, nitrates, beta-adrenergic receptor antagonists (beta-blockers), calcium channel antagonists, angiotensin-converting enzyme inhibitors, and thrombolytic agents. Current information and recommendations are presented for safe and effective use of these agents.

Topics: Cardiovascular Agents; Humans; Myocardial Ischemia

The diagnosis and treatment of patients with acute manifestations of ischemic heart disease are major public health issues. This article reviews the current state of knowledge about the problem of acute ischemic syndromes, the events leading to clinical manifestations, the key elements of the diagnosis, the therapies that can affect outcome, and the organization of systems to deal with this problem in a cost-effective manner.

Topics: Acute Disease; Cardiovascular Agents; Decision Trees; Diagnosis, Differential; Hospitalization; Humans; Myocardial Ischemia; Myocardial Reperfusion; Risk Factors

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Combined Modality Therapy; Coronary Disease; Hemodynamics; Humans; Myocardial Infarction; Myocardial Ischemia; Myocardial Revascularization; Postoperative Complications

Topics: Angina Pectoris; Calcium Channel Blockers; Cardiovascular Agents; Humans; Myocardial Ischemia

The risk of infarction and sudden death is considerable in patients with silent ischemia, whether it occurs alone or is interspersed with episodes of angina. The ischemic activity can be modified or even abolished, most effectively with beta-blocker and nitrate therapy. But it is not yet clear whether treatment improves outcome, although the limited available data suggest that it does.

Topics: Adrenergic beta-Antagonists; Cardiovascular Agents; Drug Combinations; Electrocardiography, Ambulatory; Humans; Myocardial Ischemia; Nitrates; Prognosis; Risk; Treatment Outcome

Indicators such as lowering of blood pressure in hypertension, alleviation of chest pain in angina pectoris, improvement in rest or exertional dyspnea from congestive heart failure (CHF) and suppression of ventricular arrhythmia are widely used in the management of cardiovascular diseases. There are often strong associations between the physiological indicators and the long-term clinical outcomes of cardiovascular disease such as stroke, myocardial infarction, sudden death and all-cause mortality. Physicians have assumed reasonably that early improvements in physiological markers will lead invariably to better long-term clinical outcomes. In recent years, a number of large clinical trials have demonstrated that short-term physiological improvements are not necessarily linked to better long-term clinical outcomes, but may be associated with less benefit than expected or even with detrimental outcomes. Management of cardiovascular diseases is complicated by the possibility that beneficial effects of a particular drug may be offset by its negative actions on the cardiovascular system. Effective antihypertensives may depress cardiac contractility; inotropes enhance left ventricular contractility in CHF, but may increase the risk of serious ventricular dysrhythmia; drugs which suppress ventricular arrhythmia may precipitate CHF or even excite pro-arrhythmic effects. Physicians must be conscious of this interplay of potentially beneficial and deleterious effects when cardiovascular drugs are prescribed. It is important in the analysis of large clinical trials of cardiovascular drugs to identify those situations in which the drug exhibits more benefit than harm and to determine, if possible, those aspects of drug action, drug dosage and population characteristics which contribute to the beneficial and detrimental actions.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Cardiovascular Agents; Cardiovascular Diseases; Heart Failure; Humans; Hypertension; Myocardial Ischemia; Treatment Outcome

Having thoroughly reviewed the risk factors and pathophysiologic features of ischemic heart disease, the authors describe therapeutic protocols at present in use and take stock of the perspectives opened by new drugs with different kinetic and dynamic and more advanced properties compared to those at present in use.

Topics: Cardiovascular Agents; Humans; Myocardial Ischemia; Vascular Resistance

The diagnosis of coronary artery disease in the elderly is problematic because older patients often present atypical symptoms or are asymptomatic. Once coronary disease is diagnosed, the proper course of treatment is not always clear, since few studies have focused on patients older than 65 years. Moreover, older patients often have medical conditions that may aggravate coexisting cardiovascular problems or interfere with conventional pharmacotherapy. For these reasons many physicians who treat cardiovascular problems aggressively in younger patients are reluctant to do so in older individuals. There is considerable evidence, however, that older patients could benefit as much or more from aggressive therapy because of their greater risk of mortality from myocardial ischemia and infarction.

Topics: Age Factors; Aged; Cardiovascular Agents; Cause of Death; Comorbidity; Humans; Longitudinal Studies; Myocardial Infarction; Myocardial Ischemia; Randomized Controlled Trials as Topic; Risk Factors; Survival Rate; Treatment Outcome

Primary care physicians are often faced with follow-up care of patients who have had coronary artery bypass graft surgery. Familiarity with possible cardiac, pulmonary, neurologic, and infectious complications is important, and an open line of communication with the consulting cardiologist and the cardiac surgeon is essential. Modification of coronary risk factors is one of the greatest challenges after bypass surgery. The primary care physician plays the major role in directing and monitoring life-style changes that reduce the risk of progressive coronary atherosclerosis. Recurrent myocardial ischemia after bypass surgery should be evaluated fully and is often responsive to nonsurgical therapies, including percutaneous transluminal coronary angioplasty.

Topics: Activities of Daily Living; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Bypass; Coronary Disease; Family Practice; Follow-Up Studies; Humans; Myocardial Ischemia; Platelet Aggregation Inhibitors; Postoperative Care; Postoperative Complications; Recurrence; Reoperation; Risk Factors; Time Factors

The present state of investigations on molecular and cellular mechanisms of cardioprotective effects of phosphocreatine (PCr) is reviewed. The protective effect of PCr is manifested as significant improvement of heart contractile function recovery, lowering of diastolic pressure elevation and myocardial enzymes release during postischemic reperfusion as well as better preservation of high energy phosphates in comparison with control. Data from multidisciplinary studies using physico-chemical, physiological, pharmacological etc. approaches suggest that one of the key mechanisms of PCr action is its interaction with the sarcolemmal membrane. The authors own data obtained with the use of spin-labeled ESR-probe incorporated into the isolated sarcolemmal vesicles provide direct evidence in favor of the ordering effect of PCr sarcolemmal phospholipid packing with essential involvement of Ca2+ ions. PCr transform membrane phospholipids into more structured gel-like state. The results of biomedical studies suggest that the mechanism of this protective action is complex and includes at least four components: 1) inhibition of lysophosphoglyceride accumulation in the ischemic myocardium and preservation of cardiac cell sarcolemma structure via zwitterionic interaction with PCr molecules; ii) extracellular action consisting in inhibition of platelet aggregation via ADP removal in the extracellular creatine kinase reaction and increasing plasticity of red blood cells; iii) PCr penetration into cells maintenance of high local ATP levels is possible; iiii) inhibition of adenine nucleotide degradation at the step of 5'-nucleotidase reaction in cardiac cell sarcolemma.

Topics: Animals; Calcium; Cardiovascular Agents; Cell Membrane; Heart; Myocardial Contraction; Myocardial Ischemia; Oxidation-Reduction; Phosphocreatine; Phospholipids; Sarcolemma

Topics: Adrenergic beta-Antagonists; Angina Pectoris; Calcium Channel Blockers; Cardiovascular Agents; Coronary Circulation; Electrocardiography; Humans; Myocardial Ischemia; Nitrates; Prognosis

Whether revascularization by percutaneous coronary intervention (PCI) can improve event-free survival and left ventricular function in patients with severe ischemic left ventricular systolic dysfunction, as compared with optimal medical therapy (i.e., individually adjusted pharmacologic and device therapy for heart failure) alone, is unknown.. We randomly assigned patients with a left ventricular ejection fraction of 35% or less, extensive coronary artery disease amenable to PCI, and demonstrable myocardial viability to a strategy of either PCI plus optimal medical therapy (PCI group) or optimal medical therapy alone (optimal-medical-therapy group). The primary composite outcome was death from any cause or hospitalization for heart failure. Major secondary outcomes were left ventricular ejection fraction at 6 and 12 months and quality-of-life scores.. A total of 700 patients underwent randomization - 347 were assigned to the PCI group and 353 to the optimal-medical-therapy group. Over a median of 41 months, a primary-outcome event occurred in 129 patients (37.2%) in the PCI group and in 134 patients (38.0%) in the optimal-medical-therapy group (hazard ratio, 0.99; 95% confidence interval [CI], 0.78 to 1.27; P = 0.96). The left ventricular ejection fraction was similar in the two groups at 6 months (mean difference, -1.6 percentage points; 95% CI, -3.7 to 0.5) and at 12 months (mean difference, 0.9 percentage points; 95% CI, -1.7 to 3.4). Quality-of-life scores at 6 and 12 months appeared to favor the PCI group, but the difference had diminished at 24 months.. Among patients with severe ischemic left ventricular systolic dysfunction who received optimal medical therapy, revascularization by PCI did not result in a lower incidence of death from any cause or hospitalization for heart failure. (Funded by the National Institute for Health and Care Research Health Technology Assessment Program; REVIVED-BCIS2 ClinicalTrials.gov number, NCT01920048.).

Topics: Cardiovascular Agents; Coronary Artery Disease; Heart Failure; Humans; Myocardial Ischemia; Percutaneous Coronary Intervention; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Chronic kidney disease is a known risk factor in cardiovascular disease, but its influence on treatment effect of bypass surgery remains unclear. We assessed the influence of chronic kidney disease on 10-year mortality and cardiovascular outcomes in patients with ischemic heart failure treated with medical therapy (medical treatment) with or without coronary artery bypass grafting.. We calculated the baseline estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration formula, chronic kidney disease stages 1-5) from 1209 patients randomized to medical treatment or coronary artery bypass grafting in the Surgical Treatment for IsChemic Heart failure trial and assessed its effect on outcome.. In the overall Surgical Treatment for IsChemic Heart failure cohort, patients with chronic kidney disease stages 3 to 5 were older than those with stages 1 and 2 (66-71 years vs 54-59 years) and had more comorbidities. Multivariable modeling revealed an inverse association between estimated glomerular filtration rate and risk of death, cardiovascular death, or cardiovascular rehospitalization (all P < .001, but not for stroke, P = .697). Baseline characteristics of the 2 treatment arms were equal for each chronic kidney disease stage. There were significant improvements in death or cardiovascular rehospitalization with coronary artery bypass grafting (stage 1: hazard ratio, 0.71; confidence interval, 0.53-0.96, P = .02; stage 2: hazard ratio, 0.71; confidence interval, 0.59-0.84, P < .0001; stage 3: hazard ratio, 0.76; confidence interval, 0.53-0.96, P = .03). These data were inconclusive in stages 4 and 5 for insufficient patient numbers (N = 28). There was no significant interaction of estimated glomerular filtration rate with the treatment effect of coronary artery bypass grafting (P = .25 for death and P = .54 for death or cardiovascular rehospitalization).. Chronic kidney disease is an independent risk factor for mortality in patients with ischemic heart failure with or without coronary artery bypass grafting. However, mild to moderate chronic kidney disease does not appear to influence long-term treatment effects of coronary artery bypass grafting.

Topics: Aged; Cardiovascular Agents; Coronary Artery Bypass; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Male; Middle Aged; Myocardial Ischemia; Prospective Studies; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

Prompt myocardial revascularization with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). However, as much as 50% of the loss of viable myocardium may be attributed to the reperfusion injury and the associated inflammatory response.. This study sought to evaluate the effect of the interleukin-6 receptor inhibitor tocilizumab on myocardial salvage in acute STEMI.. The ASSAIL-MI trial was a randomized, double-blind, placebo-controlled trial conducted at 3 high-volume PCI centers in Norway. Patients admitted with STEMI within 6 h of symptom onset were eligible. Consenting patients were randomized in a 1:1 fashion to promptly receive a single infusion of 280 mg tocilizumab or placebo. The primary endpoint was the myocardial salvage index as measured by magnetic resonance imaging after 3 to 7 days.. We randomized 101 patients to tocilizumab and 98 patients to placebo. The myocardial salvage index was larger in the tocilizumab group than in the placebo group (adjusted between-group difference 5.6 [95% confidence interval: 0.2 to 11.3] percentage points, p = 0.04). Microvascular obstruction was less extensive in the tocilizumab arm, but there was no significant difference in the final infarct size between the tocilizumab arm and the placebo arm (7.2% vs. 9.1% of myocardial volume, p = 0.08). Adverse events were evenly distributed across the treatment groups.. Tocilizumab increased myocardial salvage in patients with acute STEMI. (ASSessing the effect of Anti-IL-6 treatment in Myocardial Infarction [ASSAIL-MI]; NCT03004703).

Topics: Aged; Antibodies, Monoclonal, Humanized; Cardiac Imaging Techniques; Cardiovascular Agents; Coronary Occlusion; Coronary Vessels; Double-Blind Method; Female; Heart; Humans; Infusions, Intravenous; Magnetic Resonance Imaging; Male; Middle Aged; Myocardial Ischemia; Myocardium; Necrosis; Percutaneous Coronary Intervention; Receptors, Interleukin-6; ST Elevation Myocardial Infarction; Time-to-Treatment

The pathomechanisms underlying restenosis of the bioabsorbable sirolimus-eluting metallic scaffold (Magmaris) remain unknown. Using serial optical coherence tomography, we investigated causes of restenosis, including the contribution of late scaffold recoil versus neointimal hyperplasia.. Patients enrolled in BIOSOLVE-II undergoing serial angiography and optical coherence tomography (post-intervention and follow-up: 6 months and/or 1 year) were analyzed. Patients were divided into 2 groups according to angiographic in-scaffold late lumen loss (LLL) <0.5 or ≥0.5 mm. End points were late absolute scaffold recoil and neointimal hyperplasia area as assessed by optical coherence tomography.. In addition to neointimal hyperplasia, late scaffold recoil contributed significantly to LLL of sirolimus-eluting absorbable metal scaffolds. The extent of late scaffold recoil was dependent on the underlying plaque morphology and was the highest among fibrotic lesions. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01960504.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Coronary Restenosis; Coronary Vessels; Female; Fibrosis; Humans; Male; Metals; Middle Aged; Myocardial Ischemia; Neointima; Percutaneous Coronary Intervention; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tomography, Optical Coherence; Treatment Outcome

There is limited data comparing the Xience everolimus-eluting stent (EES) and the Resolute zotarolimus-eluting stent (ZES) with the BioMatrix biolimus-eluting stent (BES).. This open-label, randomized, noninferiority trial enrolled all-comer patients to be randomly treated with either BES, EES, or ZES in a 1:1:1 ratio in 15 centers across South Korea. The primary end point was a device-oriented composite outcome consisting of cardiac death, target-vessel myocardial infarction, and clinically indicated target lesion revascularization at 24 months. The BES was compared with the EES and the ZES by intention-to-treat analyses with a noninferiority margin of 3.8%, respectively.. Because of slow recruitment and low event rates, this trial was prematurely terminated after enrollment of 1935 (75%) of the intended 2580 patients. Of the 1911 patients randomized to either EES (n=638), BES (n=634), or ZES (n =639), the rate of device-oriented composite outcome was 3.6%, 2.2%, and 3.9%, respectively, at 24 months (BES versus EES: absolute risk difference -1.4% [upper limit of 1-sided 95% CI: -3.2%];. The BES was noninferior to either the EES or the ZES in all-comer patients for device-oriented composite outcome at the 24-month follow-up. However, caution is advised regarding interpretation of these results due to the premature termination of this study. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01397175.

Topics: Aged; Cardiovascular Agents; Drug-Eluting Stents; Early Termination of Clinical Trials; Everolimus; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Prosthesis Design; Recurrence; Republic of Korea; Risk Factors; Sirolimus; Treatment Outcome

Numerous randomized clinical trials have demonstrated the superiority of thin-strut biodegradable polymer second-generation drug-eluting stent to the first-generation drug-eluting stent and the noninferiority to the thin-strut second-generation permanent polymer drug-eluting stent. Data on long-term clinical outcomes with a novel ultrathin drug-eluting stent, to date, are limited.. The DESSOLVE III trial (Multicenter Randomized Study of the MiStent Sirolimus Eluting Absorbable Polymer Stent System for Revascularization of Coronary Arteries; n=1398) is a prospective, multicenter, single-blinded, all-comers, randomized controlled trial (NCT02385279), allocating in a 1:1 ratio to either ultrathin-strut biodegradable polymer MiStent sirolimus-eluting stent or to thin-strut permanent polymer Xience everolimus-eluting stent. The primary end point was device-oriented composite end point, defined as the composite of cardiac death, target vessel myocardial infarction, or clinically indicated target lesion revascularization. The secondary end point was patient-oriented composite end point, defined as the composite of all-cause mortality, any myocardial infarction, or any revascularization.. In the DESSOLVE III trial, early safety and efficacy with MiStent sirolimus-eluting bioabsorbable polymer-coated stent are confirmed at a longer term follow-up when compared with Xience everolimus-eluting permanent polymer-coated stent in a large all-comers population. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02385279.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Drug-Eluting Stents; Europe; Everolimus; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Polymers; Prospective Studies; Prosthesis Design; Risk Factors; Single-Blind Method; Time Factors; Treatment Outcome

Microvascular dysfunction is known to play a key role in patients with angina and nonobstructive coronary artery disease. We investigated the impact of ranolazine among patients with angina and nonobstructive coronary artery disease.. In this randomized, double-blinded, placebo-controlled pilot trial, 26 patients with angina once weekly or more, abnormal stress test, and nonobstructive coronary artery disease (<50% stenosis by angiography and fractional flow reserve >0.80) were randomized 1:1 to ranolazine or placebo for 12 weeks. Primary end point was ΔSeattle Angina Questionnaire (SAQ) angina frequency score. Baseline and 3 months follow-up SAQ, Duke Activity Status Index scores along with invasive fractional flow reserve, coronary flow reserve (CFR), hyperemic myocardial resistance, and cardiopulmonary exercise testing measurements were performed.. Ranolazine did not demonstrate improvement in SAQ angina frequency score, invasive microvascular function, or peak metabolic equivalent compared with placebo at 3 months. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02147067.

Topics: Atherosclerosis; Cardiovascular Agents; Double-Blind Method; Fractional Flow Reserve, Myocardial; Humans; Myocardial Ischemia; Pilot Projects; Ranolazine; Treatment Outcome

To test the effect of long-term pegfilgrastim on collateral function and myocardial ischaemia in patients with chronic stable coronary artery disease (CAD).. This was a prospective clinical trial with randomized 2:1 allocation to pegfilgrastim or placebo for 6 months. The primary study endpoint was collateral flow index (CFI) as obtained during a 1-minute ostial coronary artery balloon occlusion. CFI is the ratio of mean coronary occlusive divided by mean aortic pressure both subtracted by central venous pressure (mm Hg/mm Hg). Secondary endpoints were signs of myocardial ischaemia determined during the same coronary occlusion, that is quantitative intracoronary (i.c.) ECG ST-segment shift (mV) and the occurrence of angina pectoris. Endpoints were obtained at baseline before and at follow-up after three subcutaneous study drug injections.. Collateral flow index in the pegfilgrastim group changed from 0.096 ± 0.076 at baseline to 0.126 ± 0.070 at follow-up (P = 0.0039), while in the placebo group CFI changed from 0.157 ± 0.146 to 0.122 ± 0.043, respectively (P = 0.29); the CFI increment at follow-up was +0.030 ± 0.075 in the pegfilgrastim group and -0.034 ± 0.148 in the placebo group (P = 0.0172). In the pegfilgrastim group, i.c. ECG ST-segment shift changed from +1.23 ± 1.01 mV at baseline to +0.93 ± 0.97 mV at follow-up (P = 0.0049), and in the placebo group, it changed from +0.98 ± 1.02 mV to +1.43 ± 1.09 mV, respectively (P = 0.05). At follow-up, the fraction of patients free from angina pectoris during coronary occlusion had increased in the pegfilgrastim but not in the placebo group.. Pegfilgrastim given over the course of 6 months improves collateral function in chronic stable CAD, which is reflected by reduced myocardial ischaemia during a controlled coronary occlusion.

Topics: Cardiovascular Agents; Chronic Disease; Collateral Circulation; Coronary Artery Disease; Coronary Vessels; Female; Filgrastim; Hemodynamics; Humans; Injections, Subcutaneous; Longitudinal Studies; Male; Middle Aged; Myocardial Ischemia; Polyethylene Glycols; Prospective Studies; Treatment Outcome

The landmark STICH trial found that surgical revascularization compared to medical therapy alone improved survival in patients with heart failure (HF) of ischaemic aetiology and an ejection fraction (EF) ≤ 35%. However, the interaction between the burden of medical co-morbidities and the benefit from surgical revascularization has not been previously described in patients with ischaemic cardiomyopathy.. The STICH trial (ClinicalTrials.gov Identifier: NCT00023595) enrolled patients ≥ 18 years of age with coronary artery disease amenable to coronary artery bypass grafting (CABG) and an EF ≤ 35%. Eligible participants were randomly assigned 1:1 to receive medical therapy (MED) (n = 602) or MED/CABG (n = 610). A modified Charlson co-morbidity index (CCI) based on the availability of data and study definitions was calculated by summing the weighted points for all co-morbid conditions. Patients were divided into mild/moderate (CCI 1-4) and severe (CCI ≥ 5) co-morbidity. Cox proportional hazards models were used to evaluate the association between CCI and outcomes and the interaction between severity of co-morbidity and treatment effect. The study population included 349 patients (29%) with a mild/moderate CCI score and 863 patients (71%) with a severe CCI score. Patients with a severe CCI score had greater functional limitations based on 6-min walk test and impairments in health-related quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire. A total of 161 patients (Kaplan-Meier rate = 50%) with a mild/moderate CCI score and 579 patients (Kaplan-Meier rate = 69%) with a severe CCI score died over a median follow-up of 9.8 years. After adjusting for baseline confounders, patients with a severe CCI score were at higher risk for all-cause mortality (hazard ratio 1.44, 95% confidence interval 1.19-1.74; P < 0.001). There was no interaction between CCI score and treatment effect on survival (P = 0.756).. More than 70% of patients had a severe burden of medical co-morbidities at baseline, which was independently associated with increased risk of death. There was not a differential benefit of surgical revascularization with respect to survival based on severity of co-morbidity.

Topics: Cardiomyopathies; Cardiovascular Agents; Comorbidity; Coronary Artery Bypass; Coronary Artery Disease; Cost of Illness; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Quality of Life; Severity of Illness Index; Stroke Volume; Survival Analysis; Walk Test

The importance of glycosylated hemoglobin A1c (A1c) control as part of comprehensive risk factor management in patients with stable ischemic heart disease (SIHD) and diabetes mellitus (DM) is controversial.. The purpose of this study was to determine whether a greater number of controlled risk factors at 1 year, including A1c, affects survival in patients with DM and SIHD.. Of 690 patients with DM followed in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, 592 (86%) had complete ascertainment of 7 pre-specified risk factors at baseline and after 1 year: systolic blood pressure, low-density lipoprotein cholesterol, nonsmoking, physical activity, diet adherence, body mass index, and A1c. The primary outcome measure was mortality beyond 1 year after randomization.. During a mean follow-up of 7.0 ± 4.2 years beyond 1 year after randomization, 186 subjects died (31.4% overall, 4.5%/year). The greater the number of risk factors controlled at 1 year, the higher the probability of survival (unadjusted log rank p = 0.002). Compared with 0 to 1 controlled risk factors, attaining 3 to 7 goals predicted progressively lower mortality (hazard ratio for control of 6 or 7 risk factors was 0.13; 95% confidence interval: 0.05 to 0.40). Importantly, only 10.3% of subjects achieved control of 6 or 7 risk factors. In multivariate analysis, the strongest predictors of improved survival were no smoking, regular physical activity, dietary adherence, and A1c <7%.. In this high-risk subset of SIHD patients with DM, the number of controlled risk factors, particularly lifestyle behaviors and A1c, were associated with improved survival. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657).

Topics: Aged; Cardiovascular Agents; Cause of Death; Comorbidity; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Life Style; Male; Middle Aged; Myocardial Ischemia; Prognosis; Proportional Hazards Models; Risk Assessment; Survival Analysis

Topics: Aged; Biomarkers; Cardiovascular Agents; Defibrillators, Implantable; Electric Countershock; Exercise Tolerance; Female; Heart Failure; High-Intensity Interval Training; Humans; Inflammation Mediators; Male; Middle Aged; Myocardial Ischemia; Prospective Studies; Recovery of Function; Time Factors; Treatment Outcome

Heart failure (HF) is the end stage of many heart diseases, and ischemic heart disease (IHD) is the primary cause. Yiqi Fumai lyophilized injection, a contemporary Chinese medicine preparation, widely used in the treatment of IHF patients, shows clinical efficacy on improving symptoms and cardiac function, but the quality of the current literature does not address multiple important issues. This article describes a protocol for assessment of complementary treatment with Yiqi Fumai lyophilized injection in acute decompensated IHD.. The protocol is designed as a multicenter randomized controlled trial to assess the efficacy and safety of complementary treatment with Yiqi Fumai lyophilized injection on acute decompensated IHD. This trial will be carried out in 37 hospitals in China and expected to enroll 666 inpatients with acute decompensated IHF due to coronary heart disease. On the basis of standardized western medications, patients are randomized to either the treatment group (250 ml 5% glucose / sodium injection + 5.2 g Yiqi Fumai lyophilized injection) or the control group for 7 days and follow-up for 30 ± 3 and 60 ± 3 days. The primary outcome is change in brain natriuretic peptide (BNP) concentrations. The secondary outcomes are composite endpoint, left ventricular ejection fraction, blood troponin T/I, cardiothoracic ratio, life quality scale, scores of the four traditional Chinese medicine (TCM) diagnostic methods.. Standardized western medications together with TCM have been extensively used in China and have developed into a comprehensive treatment model. The trial will provide clinical research evidence for application of complementary treatment with intravenous Yiqi Fumai lyophilized injection on decompensated IHF.. This study protocol has been listed in the Chinese Clinical Trial Registry (registration number: ChiCTR-IPR-15007396, http://www.chictr.org.cn/showproj.aspx?proj=12370 ) on November 6, 2015.

Topics: Adult; Aged; Biomarkers; Cardiovascular Agents; China; Drug Compounding; Drugs, Chinese Herbal; Female; Freeze Drying; Heart Failure; Humans; Injections, Intravenous; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Ischemia; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Stroke Volume; Treatment Outcome; Troponin; Ventricular Function, Left

The role of implantable cardioverter-defibrillator (ICD) placement in the primary prevention of sudden cardiac death (SCD) in all consecutive patients with left ventricular ejection fraction (LVEF) ≤ 35% is still a matter of hot debate due to the fact that the population of these patients is highly heterogeneous in terms of the SCD risk. Nevertheless, reduced LVEF is still the only established criterion during qualification of patients for ICD implantation in the primary prevention of SCD, therefore identification of persons with particularly high risk among patients with LVEF ≤35% is currently of lesser importance. More important seems to be the selection of individuals with relatively low risk of SCD in whom ICD implantation can be safely postponed. The aim of the study was to determine whether well-known, non-invasive parameters, such as microvolt T-wave alternans (MTWA), baroreflex sensitivity (BRS) and short-term heart rate variability (HRV), can be helpful in the identification of low-arrhythmic risk patients with ischemic left ventricular systolic dysfunction.. In 141 patients with coronary artery disease and LVEF ≤ 35%, MTWA testing, as well as BRS and short-term HRV parameters, were analysed. During 34 ± 13 months of follow-up 37 patients had arrhythmic episode (EVENT): SCD, non-fatal sustained ventricular arrhythmia (ventricular tachycardia [VT] or ventricular fibrillation [VF]), or adequate high-voltage ICD intervention (shock) due to a rapid ventricular arrhythmia ≥200/min. LVEF, non-negative MTWA (MTWA_non-neg), BRS and low frequency power in normalized units (LFnu) turned out to be associated with the incidence of EVENT in univariate Cox analysis. The cut-off values for BRS and LFnu that most accurately distinguished between patients with and without EVENT were 3 ms/mmHg and 23, respectively. The only variable that provided 100% negative predictive value (NPV) for EVENT was negative MTWA result (MTWA_neg), but solely for initial 12 months of the follow-up; the NPVs for other potential predictors of the EVENT were lower. The cut-off values for BRS and LFnu that provide 100% NPV for EVENT during 12 and 24 months were higher: 6.0 ms/mmHg and 73 respectively, but the gain in the NPV occurred at an expense of the number of identified patients. However, the number of identified non-risk patients turned out to be higher when the predictive model included MTWA_neg and the lower cut-off values for ANS parameters: 100% NPV for 12 and 24 months of follow-up was obtained for combination MTWA_neg and BRS ≥ 3 ms/mmHg, for combination MTWA_neg and LFnu ≥ 23 100% NPV was obtained for 12 months.. Well-known, non-invasive parameters, such as MTWA, BRS and short-term HRV indices may be helpful in the identification of individuals with a relatively low risk of malignant ventricular arrhythmias among patients with ischemic left ventricular systolic dysfunction; in such persons, implantation of ICD could be safely postponed.

Topics: Aged; Baroreflex; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Female; Follow-Up Studies; Heart Rate; Humans; Male; Middle Aged; Myocardial Ischemia; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Reflex, Abnormal; Risk Assessment; Systole; Tachycardia, Ventricular; Ventricular Dysfunction, Left; Ventricular Fibrillation

Topics: Cardiac Catheterization; Cardiovascular Agents; Comparative Effectiveness Research; Conservative Treatment; Eligibility Determination; Endpoint Determination; Humans; Multicenter Studies as Topic; Myocardial Ischemia; Myocardial Revascularization; Patient Selection; Randomized Controlled Trials as Topic; Sample Size; Severity of Illness Index; Treatment Outcome

Ranolazine reduces the Na-dependent calcium overload via inhibition of the late sodium current, improving diastolic tone and oxygen handling during myocardial ischemia. In patients with angina, evidence of myocardial ischemia, but no obstructive coronary artery disease (CAD), abnormal coronary autoregulation plays a key role. Transthoracic Doppler-derived coronary flow reserve (CFR) is an index of coronary arterial reactivity and decreases in both microvascular dysfunction and coronary artery stenosis. The aim of this study was to assess the effect of ranolazine on CFR in this group of patient.. Fifty-eight (39M, 19F) patients with angina and evidence of myocardial ischemia, but no obstructive CAD, were enrolled in a double-blind, placebo-controlled trial. Participants were assigned to ranolazine (29) or placebo (29) for 8 weeks (up to 500 mg twice a day). CFR was determined as the ratio of hyperemic, induced by intravenous dypiridamole administration, to baseline diastolic coronary flow velocity. CFR was assessed before and after 8-week therapy.. CFR was successfully performed in all patients. There were no significant differences in baseline characteristics and CFR between ranolazine and placebo group. After 8 weeks CFR significantly increased in ranolazine group (2.54 ± 0.44 vs. 1.91 ± 0.31; P = 0.005) but not in placebo group (1.99 ± 0.32 vs. 1.94 ± 0.29; P = ns). No patient dropped out during 8 weeks therapy. Side effects were similar in both groups.. Ranolazine is able to improve CFR in these patients. This is probably due to improvement in abnormal coronary autoregulation, both reducing baseline diastolic coronary flow velocity and increasing hyperemic diastolic coronary flow velocity.

Topics: Cardiovascular Agents; Coronary Stenosis; Double-Blind Method; Echocardiography; Female; Fractional Flow Reserve, Myocardial; Humans; Male; Myocardial Ischemia; Placebo Effect; Ranolazine; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome

Long-term nitrate treatment of stable angina is associated with side effects that can interfere with health-related quality of life (HRQoL) and medication adherence. The aim of the present study was to compare HRQoL and adherence to treatment in patients with stable angina undergoing nitrate withdrawal or maintenance.. This study is a randomized clinical trial. Patients were allocated to an intervention group (nitrate withdrawal followed by introduction of placebo) or a control group (nitrate maintenance). The assessments were made at baseline and 30 and 120 days using the Short Form Health Survey and the Seattle Angina Questionnaire. Treatment adherence was measured on the basis of the Morisky scale and pill count.. A total of 105 patients with stable angina were randomized for replacement of nitrate with placebo (n=51) and for maintenance of treatment with nitrate (n=54). After 4 months, Short Form Health Survey scores increased for bodily pain (P=0.005) and general health (P=0.004) in the nitrate maintenance group. Decreased Seattle Angina Questionnaire scores were also noted for physical limitations (P=0.039) and angina frequency (P=0.011) in the nitrate maintenance group. However, the effect size was small (≤0.44) when the intervention and control groups were compared. At the end of the study, adherence was significantly higher in the placebo group (P=0.041), but no difference was detected between the groups with the pill count method.. HRQoL was similar in patients with stable angina using nitrate regularly as compared with patients undergoing nitrate withdrawal. However, adherence to treatment was lower in nitrate users according to the Morisky scale.

Topics: Aged; Angina, Stable; Cardiovascular Agents; Female; Humans; Male; Medication Adherence; Middle Aged; Myocardial Ischemia; Nitrates; Pain; Quality of Life; Substance Withdrawal Syndrome; Surveys and Questionnaires; Time; Treatment Outcome

to evaluate the state of the structure and function of the arterial wall in patients with chronic heart failure (CHF) of ischemic etiology in combination with persistent atrial fibrillation (AF) AF and the dynamics of their changes during therapy with omega-3 polyunsaturated fatty acids (omega-3 PUFA).. in the first phase in order to identify characteristics of a CCF and the restructuring of the arterial wall 120 patients with coronary artery disease and chronic heart failure II-III functional class (FC) were included in the study, then were divided into two equal groups according to the presence of persistent AF. In the second phase patients with CHF and persistent AF were randomized into 2 groups of 30 people to determine the vasoprotective effect of omega-3 fatty acids compared with the standard treatment of CHF. The duration of treatment was 6 months. To assess the conductive and damping functions of arteries comprehensive sfigmopletizmografiyu was carried out. To assess the state of the arteries collagen matrix we determined the level of tissue inhibitor of matrix metalloproteinases type I (TIMP-1) by enzyme immunoassay.. in patients with chronic heart failure of ischemic etiology in combination with persistent AF we revealed more severe functional impairment of the arterial wall, characterized by an increase in pulse wave velocity in carotid-femoral segment (p=0.037), the aorta (p<0.001), indexes CAVI1 (p less or equal 0.001) and augmentation (p=0.049; p<0.001) in the absence of differences in the group of patients with heart failure and sinus rhythm in terms of structural changes in collagen matrix- TIMP-1. The progress of CHF against the background persistent AF was characterized by higher levels of atrial natriuretic peptide with prevalence of diastolic dysfunction, while the more frequent co-morbidities (hypertension, diabetes mellitus type 2, stroke/transient ischemic attack), and risk factors. Inclusion in the treatment of patients with chronic heart failure of ischemic etiology and persistent AF omega-3 fatty acids provides reliable vasoprotective effect by suppressing the abnormal collagen formation on the dynamics of TIMP-1 (p<0.001) and improving the elastic properties of the arterial wall to the dynamics of high-speed data and indexed blood flow the arterial tree (p<0.001), with the exception of ankle-brachial indexes.. structurally functional remodeling of the arterial wall in patients with chronic heart failure of ischemic etiology and persistent AF has a definite pattern of forming. Omega-3 fatty acids have a vasoprotective effect, providing improving elastic properties of the arteries by preventing fibrosis.

Topics: Adult; Arteries; Atrial Fibrillation; Cardiovascular Agents; Diagnostic Techniques, Cardiovascular; Drug Monitoring; Fatty Acids, Omega-3; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Protective Agents; Severity of Illness Index; Treatment Outcome; Vascular Resistance

Study aim - to elucidate possibilities of the use of precision administration of mononuclear bone marrow cells (MBMC) for the treatment of myocardial ischemia and heart failure. "Intramyocardial Multiple Precision Administration of Mononuclear Bone Marrow Cells in the Treatment of Myocardial Ischemia" was a double blind randomized placebo controlled study in which we included patients more or equal 6 months after Q-wave myocardial infarction with systolic myocardial dysfunction (ejection fraction <35%), not requiring myocardial revascularization, receiving stable optimal medical therapy for more or equal 8 weeks, and with implanted cardioverter-defibrillator. Transplantation of MBMC was guided by fluoroscopy and tridimensional NOGA XP Cardiac Navigation System. For assessment of efficacy of the method we used surrogate end points: decrease of number of fixed perfusion defects according to SPECT data and improvement of regional myocardial contractility according to data of echocardiography. Results of dynamic observation of the first experience of MBMC administration are presented in this paper.

Topics: Adult; Bone Marrow Transplantation; Cardiovascular Agents; Double-Blind Method; Female; Heart Failure; Heart Function Tests; Humans; Male; Middle Aged; Monitoring, Physiologic; Myocardial Contraction; Myocardial Infarction; Myocardial Ischemia; Radiography, Interventional; Therapy, Computer-Assisted; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

Heart failure (HF) is associated with decreased quality of life, high re-admission rate and poor prognosis. In particular, ischemic heart failure (IHF) has a worse prognosis than nonischemic HF. The use of traditional Chinese medicine (TCM) alongside Western medicine to treat HF has developed into an integrative treatment model in China. There have been small clinical trials and experimental studies to demonstrate the efficacy of TCM for treating HF; however, there is still a lack of high-quality trials. Qishen Yiqi dripping pills (QSYQ), a TCM drug, have been commonly used alongside standardized Western medicine to treat IHF. This paper describes the protocol for the clinical assessment of QSYQ in IHF patients.. A randomized, double-blind, multicenter, placebo-controlled trial will assess the efficacy and safety of QSYQ in the treatment of IHF. The trial is to enroll 640 IHF patients from 32 hospitals in China. Besides their standardized Western medicine, patients will be randomized to receive treatment of either QSYQ or placebo for 6 months and follow-up monitoring for at least a further 6 months. The primary outcome is increased exercise capacity of patients, which will be measured using the 6-minute walking test (6MWT). The secondary outcomes include composite endpoints: all-cause mortality, frequency of hospitalization or emergency due to cardiovascular events, brain natriuretic peptide levels, left ventricular ejection fraction, and cardiothoracic ratio will be documented, as well as scores on the New York Heart Association classification and Minnesota quality of life index, and information obtained from the four TCM diagnostic methods. Blood lipid tests will also be administered.. The integrative treatment model of TCM alongside Western medicine has developed into a treatment model in China. The rigorous design of the trial will assure an objective and scientific assessment of the efficacy and safety of QSYQ in the treatment of IHF.

Topics: Biomarkers; Cardiovascular Agents; China; Double-Blind Method; Drug Therapy, Combination; Drugs, Chinese Herbal; Exercise Test; Exercise Tolerance; Heart Failure; Hospitalization; Humans; Lipids; Myocardial Ischemia; Natriuretic Peptide, Brain; Predictive Value of Tests; Quality of Life; Recovery of Function; Research Design; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left; Walking

To report the agreement between gray-scale intravascular ultrasound (GS-IVUS) and optical coherence tomography (OCT) in assessing the bioresorbable vascular scaffolds (BVS) structures and their respective reproducibility.. BVS are composed of an erodible polymer. Ultrasound and light signals backscattered from polymeric material differs from metallic stents using GS-IVUS and OCT.. Forty-five patients included in the ABSORB trial were treated with a 3.0 × 18 mm BVS and imaged with GS-IVUS 20 MHz and OCT post-implantation. Qualitative (ISA, side-branch struts, protrusion, and dissections) and quantitative (number of struts, lumen, and scaffold area) measurements were assessed by two investigators. The agreement and the inter- and intraobserver reproducibility were investigated using the kappa (κ) and the interclass correlation coefficient (ICC).. GS-IVUS and OCT agreement was predominantly poor at a lesion, frame, and strut level analysis (κ and ICC <0.4) for qualitative measurements. GS-IVUS demonstrated a reduced ability to detect cross-sections with ISA (4.5% vs. 20.6%), side-branch (SB) struts (6.3% vs. 7.8%), protrusions (3.2% vs. 9.6%), and dissections (0.2% vs. 9.0%) compared with OCT. GS-IVUS reproducibility was poor-moderate (κ and ICC <0.6) except for ISA and SB-struts (κ and ICC between 0.2 and 0.75). OCT showed an excellent reproducibility (κ and ICC > 0.75) except for the assessment of tissue protrusion (κ and ICC between 0.47 and 0.94). GS-IVUS reproducibility was poor-moderate (ICC ≤ 0.5) in assessing the number of struts but excellent with OCT (ICC > 0.85). The reproducibility to assess lumen and scaffold areas was excellent using both techniques (ICC > 0.85).. GS-IVUS has a poor capacity to detect qualitative findings post-BVS implantation and its reproducibility is low compared with OCT. The use of GS-IVUS should be limited when assessing lumen and scaffold areas.

Topics: Absorbable Implants; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Drug Carriers; Everolimus; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Observer Variation; Predictive Value of Tests; Prosthesis Design; Reproducibility of Results; Sirolimus; Time Factors; Tissue Scaffolds; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

Due to the limited distensibility of the everolimus-eluting bioresorbable vascular scaffold (ABSORB) compared to metallic platform stents, quantitative coronary arteriography (QCA) is a mandatory requirement for ABSORB deployment in the on-going ABSORB EXTEND Single-Arm Study. Visual assessment of vessel size in the ABSORB Cohort B study often lead to under and over-sizing of the 3 mm ABSORB in coronary vessels (recommended range of the vessel diameter ≥ 2.5 mm and ≤ 3.3 mm), with an increased risk of spontaneous incomplete scaffold apposition post ABSORB deployment. We report whether mandatory QCA assessment of vessel size pre-implantation, utilizing the maximal luminal diameter (Dmax) and established interpolated reference vessel diameter (RVD) measurements, has improved device/vessel sizing.. Pre-implantation post-hoc QCA analyses of all 101 patients from ABSORB Cohort B (102 lesions) and first consecutive 101 patients (108 lesions) from ABSORB EXTEND were undertaken by an independent core-laboratory; all patients had a 3 mm ABSORB implanted. Comparative analyses were performed.. Within ABSORB Cohort B, a greater number of over-sized vessels (> 3.3 mm) were identified utilizing the Dmax compared to the interpolated RVD (17 vessels, 16.7% vs. 3 vessels, 2.9%; P = 0.002). Comparative analyses demonstrated a greater number of appropriate vessel-size selection (75 vessels, 69.4% vs. 48 vessels, 47.1%; P = 0.001), a trend towards a reduction in implantation in small (< 2.5 mm) vessels (29 vessels, 26.9% vs. 40 vessels, 39.2%; P = 0.057) and a significant decrease in the implantation in large (> 3.3 mm) vessels (4 vessels, 3.7% vs. 17 vessels, 16.7%; P = 0.002) in ABSORB EXTEND. Bland-Altman plots suggested a good agreement between operator and core-laboratory calculated Dmax measurements.. The introduction of mandatory Dmax measurements of vessel size prior to ABSORB implantation significantly reduced the under-sizing of the 3.0 mm scaffold in large vessels validating the use of this technique in vessel sizing prior to ABSORB implantation.

Topics: Absorbable Implants; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Drug Carriers; Everolimus; Humans; Myocardial Ischemia; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Sirolimus; Time Factors; Tissue Scaffolds; Treatment Outcome; Ultrasonography, Interventional

The COURAGE trial reported similar clinical outcomes for patients with stable ischemic heart disease (SIHD) receiving optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI). The current post hoc substudy analysis examined the relationship between baseline stress myocardial ischemia and clinical outcomes based on randomized treatment assignment.. A total of 1,381 randomized patients (OMT n = 699, PCI + OMT n = 682) underwent baseline stress myocardial perfusion single-photon emission computed tomographic imaging. Site investigators interpreted the extent of ischemia by the number of ischemic segments using a 6-segment myocardial model. Patients were divided into those with no to mild (<3 ischemic segments) and moderate to severe ischemia (≥ 3 ischemic segments). Cox proportional hazards models were calculated to assess time to the primary end point of death or myocardial infarction.. At baseline, moderate to severe ischemia occurred in more than one-quarter of patients (n = 468), and the incidence was comparable in both treatment groups (P = .36). The primary end point, death or myocardial infarction, was similar in the OMT and PCI + OMT treatment groups for no to mild (18% and 19%, P = .92) and moderate to severe ischemia (19% and 22%, P = .53, interaction P value = .65). There was no gradient increase in events for the overall cohort with the extent of ischemia.. From the COURAGE trial post hoc substudy, the extent of site-defined ischemia did not predict adverse events and did not alter treatment effectiveness. Currently, evidence supports equipoise as to whether the extent and severity of ischemia impact on therapeutic effectiveness.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Perfusion Imaging; Proportional Hazards Models; Treatment Outcome

Topics: Brachial Artery; Cardiovascular Agents; Chronic Disease; Dose-Response Relationship, Drug; Drug Therapy, Combination; Endothelium, Vascular; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Ischemia; Treatment Outcome; Ubiquinone; Ultrasonography, Doppler, Pulsed; Vasodilation; Vitamins

We conducted a pilot study for a large definitive clinical trial evaluating the impact of ranolazine in women with angina, evidence of myocardial ischemia, and no obstructive coronary artery disease (CAD).. Women with angina, evidence of myocardial ischemia, but no obstructive CAD frequently have microvascular coronary dysfunction. The impact of ranolazine in this patient group is unknown.. A pilot randomized, double-blind, placebo-controlled, crossover trial was conducted in 20 women with angina, no obstructive CAD, and ≥ 10% ischemic myocardium on adenosine stress cardiac magnetic resonance (CMR) imaging. Participants were assigned to ranolazine or placebo for 4 weeks separated by a 2-week washout. The Seattle Angina Questionnaire and CMR were evaluated after each treatment. Invasive coronary flow reserve (CFR) was available in patients who underwent clinically indicated coronary reactivity testing. CMR data analysis included the percentage of ischemic myocardium and quantitative myocardial perfusion reserve index (MPRI).. The mean age of subjects was 57 ± 11 years. Compared with placebo, patients on ranolazine had significantly higher (better) Seattle Angina Questionnaire scores, including physical functioning (p = 0.046), angina stability (p = 0.008), and quality of life (p = 0.021). There was a trend toward a higher (better) CMR mid-ventricular MPRI (2.4 [2.0 minimum, 2.8 maximum] vs. 2.1 [1.7 minimum, 2.5 maximum], p = 0.074) on ranolazine. Among women with coronary reactivity testing (n = 13), those with CFR ≤ 3.0 had a significantly improved MPRI on ranolazine versus placebo compared to women with CFR > 3.0 (Δ in MPRI 0.48 vs. -0.82, p = 0.04).. In women with angina, evidence of ischemia, and no obstructive CAD, this pilot randomized, controlled trial revealed that ranolazine improves angina. Myocardial ischemia may also improve, particularly among women with low CFR. These data document approach feasibility and provide outcome variability estimates for planning a definitive large clinical trial to evaluate the role of ranolazine in women with microvascular coronary dysfunction. (Microvascular Coronary Disease In Women: Impact Of Ranolazine; NCT00570089).

Topics: Acetanilides; Adenosine; Aged; Cardiovascular Agents; Coronary Circulation; Cross-Over Studies; Double-Blind Method; Feasibility Studies; Female; Humans; Los Angeles; Magnetic Resonance Imaging; Microvascular Angina; Middle Aged; Myocardial Ischemia; Myocardial Perfusion Imaging; Pilot Projects; Piperazines; Placebo Effect; Quality of Life; Ranolazine; Surveys and Questionnaires; Time Factors; Treatment Outcome; Vasodilator Agents

A growing number of patients with coronary disease have refractory angina. Preclinical and early-phase clinical data suggest that intramyocardial injection of autologous CD34+ cells can improve myocardial perfusion and function.. Evaluate the safety and bioactivity of intramyocardial injections of autologous CD34+ cells in patients with refractory angina who have exhausted all other treatment options.. In this prospective, double-blind, randomized, phase II study (ClinicalTrials.gov identifier: NCT00300053), 167 patients with refractory angina received 1 of 2 doses (1×10(5) or 5×10(5) cells/kg) of mobilized autologous CD34+ cells or an equal volume of diluent (placebo). Treatment was distributed into 10 sites of ischemic, viable myocardium with a NOGA mapping injection catheter. The primary outcome measure was weekly angina frequency 6 months after treatment. Weekly angina frequency was significantly lower in the low-dose group than in placebo-treated patients at both 6 months (6.8±1.1 versus 10.9±1.2, P=0.020) and 12 months (6.3±1.2 versus 11.0±1.2, P=0.035); measurements in the high-dose group were also lower, but not significantly. Similarly, improvement in exercise tolerance was significantly greater in low-dose patients than in placebo-treated patients (6 months: 139±151 versus 69±122 seconds, P=0.014; 12 months: 140±171 versus 58±146 seconds, P=0.017) and greater, but not significantly, in the high-dose group. During cell mobilization and collection, 4.6% of patients had cardiac enzyme elevations consistent with non-ST segment elevation myocardial infarction. Mortality at 12 months was 5.4% in the placebo-treatment group with no deaths among cell-treated patients.. Patients with refractory angina who received intramyocardial injections of autologous CD34+ cells (10(5) cells/kg) experienced significant improvements in angina frequency and exercise tolerance. The cell-mobilization and -collection procedures were associated with cardiac enzyme elevations, which will be addressed in future studies.

Topics: Aged; Angina Pectoris; Antigens, CD34; Biomarkers; Blood Component Removal; Cardiovascular Agents; Coronary Circulation; Double-Blind Method; Endothelial Cells; Exercise Test; Exercise Tolerance; Female; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Least-Squares Analysis; Male; Microcirculation; Middle Aged; Myocardial Ischemia; Myocardium; Neovascularization, Physiologic; Prospective Studies; Regeneration; Regression Analysis; Risk Assessment; Risk Factors; Surveys and Questionnaires; Time Factors; Tomography, Emission-Computed, Single-Photon; Transplantation, Autologous; Treatment Outcome; United States

Perhexiline improves functional capacity in heart failure, but the mechanisms are undefined. We sought its effects on myocardial deformation in patients with viable myocardium.. Thirty-six medically-treated patients, stable at least 6 months post-infarction with LV dysfunction and myocardial viability shown by dobutamine echo (DbE) were randomised to receive perhexiline or matching placebo for 1 year. Cardiopulmonary exercise testing and DbE were performed at baseline and follow-up. Peak-systolic strain (S) and strain rate (SR) were measured offline in 111 dysfunctional segments in the placebo and 88 in the treatment group at rest, low-dose (LDD) and peak-dose dobutamine (PDD).. The serum perhexiline level was 0.27+/-0.7 microg/l. There was no difference in the wall motion response to dobutamine at baseline and follow-up. Resting strain and SR were similar in the two groups at baseline and follow-up. However, SR at LDD and PDD increased in the placebo group and worsened during the same period in the perhexiline group. Patients on perhexiline and placebo had a similar rate-pressure product and exercise duration at baseline (7.9+/-2.7 vs 8.7+/-3.3 min, p=NS) and follow-up (9.6+/-4.6 vs 10.1+/-3.03 min, p=NS).. Perhexiline does not improve the deformation of abnormal myocardial segments in patients with ischaemic LV dysfunction.

Topics: Aged; Cardiotonic Agents; Cardiovascular Agents; Dobutamine; Echocardiography; Exercise Test; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Perhexiline; Placebos; Treatment Failure; Ventricular Dysfunction, Left; Ventricular Function, Left

Compared with previous three-dimensional (3D) echocardiographic scanners, high-volume rate scanners allow higher temporal resolution and the possibility of displaying cropped images side by side. These new features make 3D echocardiography (3DE) even more attractive for application during stress. The aim of this study was to compare the feasibility and diagnostic accuracy of high-volume rate 3DE with state-of-the-art two-dimensional echocardiography (2DE) in detecting ischemia during dipyridamole-induced stress (DipSE).. One hundred seven consecutive patients with known or suspected coronary artery disease were examined using 2DE and 3DE during the same DipSE examination.. Seventeen patients with inadequate images on 2DE requiring contrast infusion and 6 patients with inadequate detection of the endocardial borders on 3DE were excluded (feasibility of 3DE, 79%). The diagnostic accuracy of 3DE with DipSE was tested in the remaining 84 patients. Both acquisition time (65 +/- 30 s vs 16 +/- 3 seconds, respectively; P < .0001) and analysis time (176 +/- 63 vs 91 +/- 5 seconds, respectively; P < .0001) were significantly longer with 2DE than 3DE. Temporal resolution was significantly higher with 2DE than 3DE (75 +/- 5 frames/s vs 41 +/- 5 volumes/s, respectively; P < .0001). The wall motion score index (WMSI) at baseline was similar with 2DE and 3DE (1.041 +/- 0.023 vs 1.049 +/- 0.01, respectively; P = NS). In contrast, peak stress WMSI was significantly lower with 2DE than 3DE (1.21 +/- 0.025 vs 1.29 +/- 0.023, respectively; P = .011). In particular, mean apical peak stress WMSI was significantly lower with 2DE than 3DE (1.34 +/- 0.057 vs 1.55 +/- 0.078, respectively; P < .0001). In the 44 patients who underwent coronary angiography, the overall accuracy of 3DE was similar to that of 2DE (sensitivity, 80% vs 78%; specificity, 87% vs 91%). In the left anterior descending coronary artery territory, for which 3DE showed higher WMSI values, the sensitivity of 3DE was significantly higher than that of 2DE (87% vs 78%, P = .011), while specificity was similar.. Three-dimensional echocardiography with DipSE is feasible and offers shorter acquisition and analysis times compared with 2DE, with similar overall diagnostic accuracy. However, the ability of 3DE to identify wall motion abnormalities in the apical region explains its higher sensitivity for the left anterior descending coronary artery territory.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Coronary Artery Disease; Dipyridamole; Echocardiography; Echocardiography, Stress; Echocardiography, Three-Dimensional; Feasibility Studies; Female; Heart; Humans; Male; Middle Aged; Myocardial Ischemia

This study evaluates cardiovascular risk factors associated with progression of coronary artery disease (CAD) in patients with silent ischemia following myocardial infarction.. Coronary artery disease only progresses slowly with comprehensive risk factor intervention.. A total of 104 of 201 patients (51.7%) of the Swiss Interventional Study on Silent Ischemia Type II (SWISSI II) with baseline and follow-up coronary angiography were included. All patients received comprehensive cardiovascular risk factor intervention according to study protocol. Logistic regression was used to evaluate associations between baseline cardiovascular risk factors and CAD progression.. The mean duration of follow-up was 10.3+/-2.4 years. At baseline, 77.9% of patients were smokers, 45.2% had hypertension, 73.1% had dyslipidemia, 7.7% had diabetes, and 48.1% had a family history of CAD. At last follow-up, only 27 patients of the initial 81 smokers still smoked, only 2.1% of the patients had uncontrolled hypertension, 10.6% of the patients had uncontrolled dyslipidemia, and 2.1% of the patients had uncontrolled diabetes. Coronary artery disease progression was found in up to 81 (77.9%) patients. Baseline diabetes and younger age were associated with increased odds of CAD progression. The time interval between baseline and follow-up angiography was also associated with CAD progression.. Coronary artery disease progression was highly prevalent in these patients despite comprehensive risk factor intervention. Further research is needed to optimize treatment of known risk factors and to identify other unknown and potentially modifiable risk factors.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Antihypertensive Agents; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Stenosis; Disease Progression; Female; Humans; Hypoglycemic Agents; Hypolipidemic Agents; Logistic Models; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Odds Ratio; Risk Assessment; Risk Factors; Severity of Illness Index; Smoking Cessation; Switzerland; Time Factors

To evaluate the effect of the I(f) channel blocker ivabradine on bronchial patency and the volume parameters of external respiration function in patients with chronic obstructive pulmonary disease (COPD) in remission in order to determine whether the drug may be used in patients with coronary heart disease (CHD) concurrent with COPD.. Heart rate, bronchial patency, and lung volume were studied by body plethysmography in 59 patients with COPD before and 14 days after administration of ivabradine in a daily dose of 10 mg.. The I(f) channel blocker ivabradine that is a highly selective bradycardiac agent fails to affect the velocity and volume parameters of external respiration function, thus it may be used to treat CHD concurrent with COPD.. The I(f) channel blocker ivabradine exerts no effect on external respiration function parameters (bronchial patency, volume parameters) and it can find clinical use in the treatment of angina pectoris and chronic heart failure in patients with CHD concurrent with COPD.

Topics: Aged; Benzazepines; Cardiovascular Agents; Cyclic Nucleotide-Gated Cation Channels; Electrocardiography; Female; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Myocardial Ischemia; Pulmonary Disease, Chronic Obstructive; Respiration; Respiratory Function Tests

Hepatocyte growth-promoting factor (pHGF) has the greatest potential as a therapeutic agent for vascular growth factor. The aim of this study was to investigate the effect of pHGF on myocardial ischemia and exercise capacity in patients with severe coronary artery disease (CAD). Forty-nine patients were enrolled for a two week treatment period. Treadmill graded exercise tests with gas analysis were conducted before and after therapy. Serum levels of HGF were significantly elevated after therapy. The degrees of exercise-induced ST segment depression were decreased more significantly in the pHGF group. Similar differences were also found in the maximum heart rate and the maximum heart rate when the ST segment was depressed 1 mm while undergoing the treadmill graded exercise test. Both were increased more significantly in the pHGF group. Total exercise time, systolic blood pressure in the peak of exercise, the length of time that ST segment depression of 1 mm is needed, and total work all were increased in both groups after intervention. Furthermore, total exercise time and total work were increased more significantly in the pHGF group. The levels of HGF increased significantly after pHGF treatment. pHGF could favorably improve exercise-induced myocardial ischemia and enhance exercise capacity in patients with severe CAD.

Topics: Aged; Aged, 80 and over; Blood Pressure; Cardiovascular Agents; Coronary Artery Disease; Double-Blind Method; Drug Therapy, Combination; Echocardiography, Doppler, Color; Electrocardiography; Exercise Test; Female; Heart Rate; Hepatocyte Growth Factor; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Ischemia; Prospective Studies; Stroke Volume

Adenosine plays a key role in different protective and adaptive responses to ischemia and has been suggested to induce ischemic preconditioning.. To investigate whether a low-dose adenosine infusion reduces the ischemic burden induced by pharmacological stress without affecting the coronary flow reserve (CFR).. Myocardial ischemia was induced by dobutamine stress test and quantified by tissue Doppler echocardiography in 11 patients with advanced coronary artery disease. CFR was quantified during high-dose adenosine infusion by contrast echocardiography. Before the dobutamine stress test and contrast echocardiography, intravenous low-dose adenosine or placebo was infused over 15 min according to a randomized, double-blind, cross-over protocol. Echocardiographic left ventricular (LV) apical images and flow pattern of left anterior descending coronary artery (LAD) were obtained at baseline, during adenosine/placebo infusion, maximal, and recovery phases.Furthermore, the LV walls were categorized as ischemic or nonischemic according to a predefined ischemic threshold of at least 25% increment in peak systolic velocity (PSV)from baseline to maximal stress. CFR was measured as the ratio of peak/baseline of maximal diastolic velocity in the distal LAD.. PSV increased both during placebo and adenosine infusions from baseline to maximal stress. However, in the ischemic walls, the PSV increased only during adenosine infusion, whereas no differences were observed in the nonischemic walls. There were no differences in blood pressure, heart rate, or regional CFR during placebo or adenosine infusion.. Low-dose adenosine infusion improves regional LV systolic function in the ischemic walls, without any effect on CFR, suggesting that the observed improvement may be because of ischemic preconditioning.

Topics: Adenosine; Aged; Cardiovascular Agents; Contrast Media; Coronary Artery Disease; Cross-Over Studies; Double-Blind Method; Echocardiography, Doppler; Echocardiography, Stress; Female; Fractional Flow Reserve, Myocardial; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Contraction; Myocardial Ischemia; Severity of Illness Index; Treatment Outcome; Ventricular Function, Left

This study examined the hypothesis that the improvement in myocardial blood flow (MBF) with ranolazine therapy could be detected by serial automated quantitative myocardial perfusion imaging (MPI) in patients with coronary artery disease (CAD) and myocardial ischemia.. Myocardial ischemia enhances late sodium current, which then causes cellular calcium overload leading to mechanical left ventricular dysfunction and arrhythmias. Ranolazine inhibits late sodium current and improves diastolic tension and MBF in the animal model.. In this open-label, nonrandomized pilot study, we recruited 20 patients with known or a high probability of CAD and who had reversible perfusion defects on exercise treadmill gated single-photon emission computed tomography MPI while receiving conventional antianginal therapy. Ranolazine (up to 1,000 mg twice daily) was added to baseline therapy and a repeat treadmill MPI was obtained after 4 weeks. The extent and severity of total and reversible left ventricular perfusion abnormality (based on polar maps and a 17-segment model) were determined quantitatively using automated methods.. We screened 100 patients for 27 potential candidates; 5 declined and 2 did not complete the follow-up study. The mean age of the remaining 20 patients was 64 +/- 9 years; 30% were women and 50% had diabetes mellitus. The exercise time increased (425 +/- 105 s vs. 393 +/- 116 s, p = 0.017), and angina improved in 15 (75%) patients after ranolazine treatment. In the entire cohort, summed stress scores (10 +/- 7 vs. 13 +/- 8, p = 0.04) and summed difference scores (4.7 +/- 4 vs. 7.4 +/- 5, p = 0.0037) decreased at follow-up. An improvement in perfusion pattern and severity was noted in 14 (70%) patients. In these patients, the polar maps showed a decrease in total abnormality from 26 +/- 17% to 19 +/- 15% and a decrease in the reversible abnormality from 16 +/- 10% to 8 +/- 6% (all p values <0.05).. In this preliminary hypothesis-driven study, short-term ranolazine therapy was shown to improve myocardial perfusion and decrease the ischemic burden in patients with CAD.

Topics: Acetanilides; Aged; Angina Pectoris; Automation, Laboratory; Cardiovascular Agents; Coronary Artery Disease; Coronary Circulation; Exercise Test; Exercise Tolerance; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Perfusion Imaging; Pilot Projects; Piperazines; Ranolazine; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

This article reports the 2-year clinical, angiographic, and intravascular ultrasound outcomes of the everolimus-eluting stent (EES) compared with the paclitaxel-eluting stent (PES) in the randomized SPIRIT II trial.. This was a prospective, single-blind clinical trial in which a total of 300 patients with de novo native coronary artery lesions were randomized to either EES or PES in a 3:1 fashion. Clinical follow-up was planned at 2 years in all patients. A subset of 152 patients underwent serial angiographic and intravascular ultrasound analyses at 6 months and 2 years. After 2 years, target lesion failure (cardiac death, myocardial infarction, and ischemia-driven target lesion revascularization) rates were 6.6% and 11% in EES and PES, respectively (P=0.31). At 6 months, a significant reduction in angiographic in-stent late loss and percentage volume obstruction measured by intravascular ultrasound was observed in the EES group. However, at 2-year follow-up, a late increased intimal hyperplasia growth after implantation of an EES was observed. There were no significant differences between EES and PES for in-stent late loss (EES, 0.33+/-0.37 mm versus PES, 0.34+/-0.34 mm; P=0.84) and percentage volume obstruction (EES, 5.18+/-6.22% versus PES, 5.80+/-6.31%; P=0.65) at 2 years. The incidence of stent thrombosis was low and comparable in both groups (EES, 0.9%; PES, 1.4%).. Although the previously reported angiographic and clinical superiority of the EES has vanished over time, this report confirms and extends the previously demonstrated noninferiority in terms of in-stent late loss of the EES when compared with the PES up to 2-year follow-up. There were no significant differences between EES and PES in clinical, angiographic and intravascular ultrasound outcomes at 2 years.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Drug-Eluting Stents; Europe; Everolimus; Female; Humans; India; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; New Zealand; Paclitaxel; Prospective Studies; Single-Blind Method; Sirolimus; Thrombosis; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Ranolazine is a novel antianginal agent that reduces ischemia in patients with chronic angina but has not been studied in patients with acute coronary syndromes (ACS).. To determine the efficacy and safety of ranolazine during long-term treatment of patients with non-ST-elevation ACS.. A randomized, double-blind, placebo-controlled, multinational clinical trial of 6560 patients within 48 hours of ischemic symptoms who were treated with ranolazine (initiated intravenously and followed by oral ranolazine extended-release 1000 mg twice daily, n = 3279) or matching placebo (n = 3281), and followed up for a median of 348 days in the Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes (MERLIN)-TIMI 36 trial between October 8, 2004, and February 14, 2007.. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction (MI), or recurrent ischemia through the end of study. The major safety end points were death from any cause and symptomatic documented arrhythmia.. The primary end point occurred in 696 patients (21.8%) in the ranolazine group and 753 patients (23.5%) in the placebo group (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.83-1.02; P = .11). The major secondary end point (cardiovascular death, MI, or severe recurrent ischemia) occurred in 602 patients (18.7%) in the ranolazine group and 625 (19.2%) in the placebo group (HR, 0.96; 95% CI, 0.86-1.08; P = .50). Cardiovascular death or MI occurred in 338 patients (10.4%) allocated to ranolazine and 343 patients (10.5%) allocated to placebo (HR, 0.99; 95% CI, 0.85-1.15; P = .87). Recurrent ischemia was reduced in the ranolazine group (430 [13.9%]) compared with the placebo group (494 [16.1%]; HR, 0.87; 95% CI, 0.76-0.99; P = .03). QTc prolongation requiring a reduction in the dose of intravenous drug occurred in 31 patients (0.9%) receiving ranolazine compared with 10 patients (0.3%) receiving placebo. Symptomatic documented arrhythmias did not differ between the ranolazine (99 [3.0%]) and placebo (102 [3.1%]) groups (P = .84). No difference in total mortality was observed with ranolazine compared with placebo (172 vs 175; HR, 0.99; 95% CI, 0.80-1.22; P = .91).. The addition of ranolazine to standard treatment for ACS was not effective in reducing major cardiovascular events. Ranolazine did not adversely affect the risk of all-cause death or symptomatic documented arrhythmia. Our findings provide support for the safety and efficacy of ranolazine as antianginal therapy.. clinicaltrials.gov Identifier: NCT00099788.

Topics: Acetanilides; Aged; Angina Pectoris; Cardiovascular Agents; Double-Blind Method; Enzyme Inhibitors; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Piperazines; Proportional Hazards Models; Ranolazine; Recurrence

Analysis of the 3-year outcome of the original population of the TAXi trial which compared the efficacy of the paclitaxel (PES) and the sirolimus (SES) stents in a randomized "real world" investigation.. The widespread use of drug-eluting stents strongly modified the world of interventional cardiology. The TAXi trial was a randomized comparison between PES and SES and showed similar efficacy between the two prostheses. Recently, emerging discussions raised questions about potential long-term risk with the use of DES. The present work attempts to describe the long-term outcome of the patients compared during the TAXi trial.. During April 2003 and January 2004, 202 patients were prospectively randomly assigned to the PES group (102 patients) and to the SES group (100 patients). The primary aim of the present investigation was the comparison of combined incidence of cardiac death, myocardial infarction, and target lesion revascularization within 36-months.. No difference in mortality of all causes was noted in the PES and the SES groups (3% vs. 7%, P=0.98) or in major adverse cardiac event free survival (89% vs. 83%, P=0.28). Four stent thromboses were observed, two in the PES group (205 and 788 days) and two in the SES group (210 and 772 days).. The long-term outcome analysis of the TAXi trial confirms available published data showing the equivalence of PES and SES on clinical basis.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cardiovascular Diseases; Female; Follow-Up Studies; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Paclitaxel; Prospective Studies; Prosthesis Design; Research Design; Sirolimus; Stents; Thrombosis; Time Factors; Treatment Outcome

The rationale and design of the Surgical Treatment for Ischemic Heart Failure trial is described. Before the Surgical Treatment for Ischemic Heart Failure trial, less than 1000 patients with ischemic cardiomyopathy had been studied in randomized comparisons of medical therapy versus coronary artery bypass grafting. Trial data reflect how these therapies were delivered more than 20 years ago and do not indicate the relative benefits of medical therapy versus coronary artery bypass grafting in contemporary practice.. Randomization of consenting patients with heart failure, left ventricular ejection fraction of 0.35 or less, and coronary artery disease is based on whether patients are judged by attending physicians to be candidates only for coronary artery bypass grafting or can be treated with medical therapy without coronary artery bypass grafting. Patients eligible for surgical ventricular reconstruction because of significant anterior wall akinesis or dyskinesis but ineligible for medical therapy are randomly assigned to coronary artery bypass grafting with or without surgical ventricular reconstruction. Patients eligible for medical therapy are randomly assigned between medical therapy only and medical therapy with coronary artery bypass grafting. Patients eligible for all 3 are randomly assigned evenly to medical therapy only, medical therapy and coronary artery bypass grafting, or medical therapy and coronary artery bypass grafting and surgical ventricular reconstruction. Major substudies will examine quality of life, cost-effectiveness, changes in left ventricular volumes, effect of myocardial viability, selected biomarkers, and selected polymorphisms on treatment differences.. Enrollment is now complete in both STICH hypotheses. Follow-up will continue until sufficient end points are available to address both hypotheses with at least 90% power. The primary outcome of hypothesis 2 is expected to be reported in 2009. The primary outcome of hypothesis 1 is expected to be reported in 2011.. The Surgical Treatment for Ischemic Heart Failure trial is a National Heart, Lung, and Blood Institute-funded multicenter international randomized trial addressing 2 specific primary hypotheses: (1) coronary artery bypass grafting with intensive medical therapy improves long-term survival compared with survival with medical therapy alone, and (2) in patients with anterior left ventricular dysfunction, surgical ventricular reconstruction to a more normal left ventricular size plus coronary artery bypass grafting improves survival free of subsequent hospitalization for cardiac cause when compared with that with coronary artery bypass grafting alone.

Topics: Adult; Cardiac Surgical Procedures; Cardiovascular Agents; Coronary Artery Bypass; Female; Heart Failure; Heart Ventricles; Humans; Male; Myocardial Ischemia; Randomized Controlled Trials as Topic; Research Design; Survival Analysis

Chronic heart failure (CHF) is a major cause of morbidity and mortality that requires a novel approach to therapy. Perhexiline is an antianginal drug that augments glucose metabolism by blocking muscle mitochondrial free fatty acid uptake, thereby increasing metabolic efficiency. We assessed the effects of perhexiline treatment in CHF patients.. In a double-blind fashion, we randomly assigned patients with optimally medicated CHF to either perhexiline (n=28) or placebo (n=28). The primary end point was peak exercise oxygen consumption (VO2max), an important prognostic marker. In addition, the effect of perhexiline on myocardial function and quality of life was assessed. Quantitative stress echocardiography with tissue Doppler measurements was used to assess regional myocardial function in patients with ischemic CHF. 31P magnetic resonance spectroscopy was used to assess the effect of perhexiline on skeletal muscle energetics in patients with nonischemic CHF. Treatment with perhexiline led to significant improvements in VO2max (16.1+/-0.6 to 18.8+/-1.1 mL . kg(-1) . min(-1); P<0.001), quality of life (Minnesota score reduction from 45+/-5 to 34+/-5; P=0.04), and left ventricular ejection fraction (24+/-1% to 34+/-2%; P<0.001). Perhexiline treatment also increased resting and peak dobutamine stress regional myocardial function (by 15% and 24%, respectively) and normalized skeletal muscle phosphocreatine recovery after exercise. There were no adverse effects during the treatment period.. In patients with CHF, metabolic modulation with perhexiline improved VO2max, left ventricular ejection fraction, symptoms, resting and peak stress myocardial function, and skeletal muscle energetics. Perhexiline may therefore represent a novel treatment for CHF with a good safety profile, provided that the dosage is adjusted according to plasma levels.

Topics: Aged; Cardiovascular Agents; Chronic Disease; Echocardiography, Stress; Fatty Acids; Female; Glucose; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardium; Oxygen Consumption; Perhexiline; Quality of Life; Stroke Volume; Treatment Outcome

The article substantiates the necessity to administer the antioxidants--vitamins E and ascorbic acid--to patients suffering from coronary heart disease with type II hyperlipoproteinemia in addition to basic therapy, and demonstrates their efficacy and safety. The authors discuss the mechanism of the positive effect of these antioxidants on lipid peroxidation and the blood content of atherogenic lipoproteins.

Topics: Adult; Antioxidants; Biomarkers; Cardiovascular Agents; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Hyperlipoproteinemia Type II; Lipid Peroxidation; Lipoproteins; Male; Middle Aged; Myocardial Ischemia; Treatment Outcome

Many patients with chronic angina experience anginal episodes despite revascularization and antianginal medications. In a previous trial, antianginal monotherapy with ranolazine, a drug believed to partially inhibit fatty acid oxidation, increased treadmill exercise performance; however, its long-term efficacy and safety have not been studied in combination with beta-blockers or calcium antagonists in a large patient population with severe chronic angina.. To determine whether, at trough levels, ranolazine improves the total exercise time of patients who have symptoms of chronic angina and who experience angina and ischemia at low workloads despite taking standard doses of atenolol, amlodipine, or diltiazem and to determine times to angina onset and to electrocardiographic evidence of myocardial ischemia, effect on angina attacks and nitroglycerin use, and effect on long-term survival in an open-label observational study extension.. A randomized, 3-group parallel, double-blind, placebo-controlled trial of 823 eligible adults with symptomatic chronic angina who were randomly assigned to receive placebo or 1 of 2 doses of ranolazine. Patients treated at the 118 participating ambulatory outpatient settings in several countries were enrolled in the Combination Assessment of Ranolazine In Stable Angina (CARISA) trial from July 1999 to August 2001 and followed up through October 31, 2002.. Patients received twice-daily placebo or 750 mg or 1000 mg of ranolazine. Treadmill exercise 12 hours (trough) and 4 hours (peak) after dosing was assessed after 2, 6 (trough only), and 12 weeks of treatment.. Change in exercise duration, time to onset of angina, time to onset of ischemia, nitroglycerin use, and number of angina attacks.. Trough exercise duration increased by 115.6 seconds from baseline in both ranolazine groups (pooled) vs 91.7 seconds in the placebo group (P =.01). The times to angina and to electrocardiographic ischemia also increased in the ranolazine groups, at peak more than at trough. The increases did not depend on changes in blood pressure, heart rate, or background antianginal therapy and persisted throughout 12 weeks. Ranolazine reduced angina attacks and nitroglycerin use by about 1 per week vs placebo (P<.02). Survival of 750 patients taking ranolazine during the CARISA trial or its associated long-term open-label study was 98.4% in the first year and 95.9% in the second year.. Twice-daily doses of ranolazine increased exercise capacity and provided additional antianginal relief to symptomatic patients with severe chronic angina taking standard doses of atenolol, amlodipine, or diltiazem, without evident adverse, long-term survival consequences over 1 to 2 years of therapy.

Topics: Acetanilides; Adrenergic beta-Antagonists; Aged; Amlodipine; Angina Pectoris; Atenolol; Calcium Channel Blockers; Cardiovascular Agents; Chronic Disease; Diltiazem; Double-Blind Method; Drug Therapy, Combination; Electrocardiography; Exercise Test; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Nitroglycerin; Physical Exertion; Piperazines; Ranolazine; Survival Analysis

Resynchronization therapy by simultaneous pacing of the right and left ventricles has gained wide acceptance as a useful treatment for patients with severe congestive heart failure. Several short-term hemodynamic studies in humans and animals failed to demonstrate any benefit of biventricular pacing over left univentricular pacing, but long-term studies on this pacing mode are lacking. The objective of this study was to assess the outcome over a 1-year period of patients paced exclusively in the left ventricle.. Clinical, angiographic, echocardiographic, and ergometric data were collected at baseline and after 12 months in 22 patients (age, 69.3+/-6.5 years) with NYHA class III or IV (10 patients), sinus rhythm, left bundle-branch block, and no bradycardia indication for pacing. After 12 months, compared with baseline values, NYHA class improved significantly by 40% (P<0.0001), 6-minute walk distance by 30% (P=0.01), peak VO2 by 26% (P=0.01), left ventricular end-diastolic diameter by 5% (P=0.02), ejection fraction by 22% (P=0.07), mitral regurgitation area by 40% (P=0.01), and norepinephrine level by 37% (P=0.04).. In patients with severe congestive heart failure, sinus rhythm, and left bundle-branch block despite optimal pharmacological treatment, left univentricular pacing is feasible and results in significant midterm benefit in exercise tolerance and left ventricular function.

Topics: Aged; Bundle-Branch Block; Cardiac Pacing, Artificial; Cardiovascular Agents; Combined Modality Therapy; Coronary Angiography; Diuretics; Exercise Tolerance; Female; Follow-Up Studies; Heart Failure; Heart Ventricles; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Myocardial Ischemia; Norepinephrine; Oxygen Consumption; Prospective Studies; Stroke Volume; Treatment Outcome; Ultrasonography; Walking

Stent implantation for isolated stenosis of the proximal left anterior descending coronary artery (LAD) with preserved left ventricular function has been found to have a better clinical and angiographic outcome at one year than balloon angioplasty (PTCA).. To establish whether those results are maintained at five year follow up.. Patients were followed at least every six months. For those who died during follow up, data were obtained from medical records.. Freedom from death, non-fatal myocardial infarction, cerebrovascular accident, and repeated target lesion revascularisation. Secondary end points were revascularisation in a remote region and freedom from angina.. Follow up was complete in all patients. At five years, the primary end point was reached more often by patients randomised to stent implantation than to PTCA (80% v 53%; odds ratio (OR) 0.29 (95% confidence interval (CI) 0.13 to 0.69); p = 0.0034). In the PTCA group, 35% of patients underwent target lesion revascularisation v 15% in the stent group (OR 0.33, 95% CI 0.13 to 0.80; p = 0.014). There was a trend towards increased mortality in the PTCA group than in the stent group (17% v 7%; OR 0.36, 95% CI 0.10 to 1.21; p = 0.098). No significant differences were found between PTCA and stent groups for non-fatal myocardial infarction (8% v 5%; OR 0.58, 95% CI 0.13 to 2.54; p = 0.46) or cerebrovascular accident (2% v 0%).. In patients with isolated stenosis of the proximal LAD, a five year clinical follow up confirmed a better outcome in those treated with stenting than with PTCA.

Topics: Acute Disease; Angina Pectoris; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Stenosis; Follow-Up Studies; Humans; Myocardial Infarction; Myocardial Ischemia; Myocardial Revascularization; Stents; Treatment Outcome

The utility of N-terminal proBNP (NT-proBNP) to predict the occurrence of death and hospitalization was prospectively evaluated in the COPERNICUS study, which enrolled patients with an ejection fraction <25% and symptoms of chronic congestive heart failure at rest or on minimal exertion.. Baseline plasma concentrations of NT-proBNP were measured in a subgroup of 814 men and 197 women with symptoms at rest or on minimal exertion who were enrolled in the COPERNICUS study and were randomized to placebo (n=506) or carvedilol (n=505). Values of NT-proBNP were markedly increased despite the requirement that patients be euvolemic before the start of treatment (mean+/-SD, 3235+/-4392 pg/mL; median, 1767 pg/mL). By univariate Cox regression analysis, NT-proBNP was found to be a powerful predictor of subsequent all-cause mortality (relative risk [RR], 2.7; 95% CI, 1.7 to 4.3; P=0.0001 for above versus below median) and all-cause mortality or hospitalization for heart failure (RR, 2.4; 95% CI, 1.8 to 3.4; P=0.0001 for above versus below median). The predictive value of NT-proBNP was similar when both placebo and carvedilol patients were analyzed separately. No significant interaction was found between NT-proBNP and treatment group (P=0.93 for above- versus below-median NT-proBNP).. NT-proBNP was consistently associated with increased risk for all-cause mortality and for all-cause mortality or hospitalization for heart failure in patients with severe congestive heart failure, even in those who were clinically euvolemic. This marker therefore may be a useful tool in risk stratification of patients with severe congestive heart failure.

Topics: Adrenergic beta-Antagonists; Aged; Biomarkers; Blood Pressure; Carbazoles; Cardiovascular Agents; Carvedilol; Creatinine; Drug Therapy, Combination; Europe; Female; Heart Failure; Hospitalization; Humans; Life Tables; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Predictive Value of Tests; Prognosis; Propanolamines; Proportional Hazards Models; Prospective Studies; Stroke Volume; Survival Analysis

Ischemic heart disease patients (20 men, 20 women, age 36-72 years) with class II-III effort angina and depression (Beck Depression Inventory -- BDI -- score > or = 19) were randomized to standard therapy were treatment of stable ischemic heart disease (control group) or standard therapy plus tianeptine 37.5 mg/day. After 6 weeks 52% decrease of BDI score occurred in tianeptine treated patients (from 24.9+/-1.2 to 11.9+/-1.5, p<0.001). This was associated with decrease of number and severity of cardialgias, better blood pressure control in patients with hypertension, lengthening of exercise time during exercise test (by 3.3+/-0.9 min, p<0.05), and increase of overall index of quality of life (by 2.6+/-0.9 points, p<0.01). No dynamics of these parameters occurred in control group.

Topics: Adult; Aged; Antidepressive Agents, Tricyclic; Cardiovascular Agents; Depression; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Quality of Life; Risk Factors; Thiazepines; Time Factors; Treatment Outcome

The deterioration of the long-term fractal component of heart rate variability (beta) is reported in patients with organic heart disease. To examine the day-to-day variability of beta and to study the effects of nipradilol (NIP), an antianginal agent, on beta in patients with coronary artery disease (CAD), we performed 24-hour ambulatory ECG (AECG) in 24 patients with silent myocardial ischemia (SMI) and obtained the conventional frequency domain heart rate variability (HRV) indices and beta using the MemCalc system. Patients were divided into two groups: group I consisted of 10 patients (64 +/- 5 years of age) for the assessment of the day-to-day variability of beta; group II comprised 14 patients (60 +/- 6 years of age) for evaluation of the effect of NIP (3 mg b.i.d). In group I, AECG was repeated twice a week, while AECG was recorded before NIP treatment (placebo) and on the last day of the 4-week NIP treatment in group II. In group I, there was significant correlation between the values of beta on day 1 and day 2 (r = 0.79, p < 0.05), the difference being 0.09 +/- 0.15 (coefficient of variance: 6.8%). Bland and Altman's analysis indicated that the results were easily reproducible, making this approach feasible for clinical use. In group II, NIP significantly decreased the values of beta by 10.6% (from -1.23 +/- 0.09 to -1.18 +/- 0.07; p < 0.05). NIP also significantly increased the conventional HRV indices. The degree of decrement of beta by NIP was larger than that of the day-to-day variability. In conclusion, a day-to-day variability exists in beta in patients with SMI, but its value is relatively small. A daily dose of 6 mg NIP ameliorates beta and overcomes this variability.

Topics: Adrenergic alpha-Antagonists; Blood Pressure; Cardiovascular Agents; Circadian Rhythm; Drug Administration Schedule; Electrocardiography, Ambulatory; Female; Fractals; Heart Rate; Humans; Japan; Male; Middle Aged; Myocardial Ischemia; Propanolamines; Single-Blind Method

We sought to determine whether a potent Rho-kinase inhibitor fasudil prevents the occurrence of myocardial ischemia in patients with microvascular angina attributable to coronary microvascular spasm.. Effective treatment of patients with angina who have normal coronary arteriograms (microvascular angina) has not yet been established. Rho-kinase-mediated calcium sensitization of the myosin light chain in smooth muscle cells has been implicated as substantially contributing to vascular hyperconstriction.. We studied consecutive 18 patients with angina and normal epicardial coronaries in whom intracoronary acetylcholine (ACh) induced myocardial ischemia (ischemic electrocardiographic changes, myocardial lactate production, or both) without angiographically demonstrable epicardial coronary vasospasm. All patients underwent a second ACh challenge test after pretreatment with either saline (n = 5) or fasudil (4.5 mg intracoronarily, n = 13).. Myocardial ischemia was reproducibly induced by ACh in the saline group. In contrast, 11 of the 13 patients pretreated with fasudil had no evidence of myocardial ischemia during the second infusion of ACh (p < 0.01). The lactate extraction ratio (median value [interquartile range]) during ACh infusion was improved by fasudil pretreatment, from -0.16 (-0.25 to 0.04) to 0.09 (0.05 to 0.18) (p = 0.0125).. Fasudil ameliorated myocardial ischemia in patients who were most likely having coronary microvascular spasm. The inhibition of Rho-kinase may be a novel therapeutic strategy for this group of patients with microvascular angina.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Acetylcholine; Aged; Cardiovascular Agents; Coronary Circulation; Coronary Vasospasm; Enzyme Inhibitors; Female; Heart Function Tests; Humans; Infusions, Intra-Arterial; Intracellular Signaling Peptides and Proteins; Microvascular Angina; Middle Aged; Myocardial Ischemia; Protein Serine-Threonine Kinases; rho-Associated Kinases; Treatment Outcome; Vasodilator Agents

To study effects of the drug pumpan on exercise tolerance and myocardial ischemia induced by exercise in patients with ischemic heart disease of functional class II-III.. The study included 30 patients with various forms of ischemic heart disease (myocardial infarction, coronary artery bypass grafting) having stable effort angina of functional class II-III.. The addition of a compound drug pumpan to a standard antianginal therapy reduced the number of anginal attacks and ST depression at bicycle exercise test.. Pumpan is an adjuvant medication in conduction of antianginal therapy in ischemic heart disease patients with stable angina of effort of functional class II-III.

Topics: Blood Pressure; Cardiovascular Agents; Drug Therapy, Combination; Electrocardiography; Exercise Tolerance; Female; Heart Rate; Homeopathy; Humans; Male; Middle Aged; Myocardial Ischemia; Treatment Outcome

To compare the impact of therapy with dialtiazem and enapril on myocardial ischemia, this randomized study included 25 patients with chronic obstructive bronchitis and myocardial ischemia. A comparative assessment of the results of therapy showed a uniform time course of changes in the parameters of Holter monitoring and bicycle ergometry (BEM). In a group of patients receiving dialthizem, there were reduces in the number of episodes of painful and silent ischemia by 66.6 and 72.2%, respectively; the duration of myocardial ischemia and the value of the maximum ST depression decreased by 47.4%. In patients receiving enalapril, the episodes of painful and silent ischemia became fewer by 55.9 and 63.6%, respectively; the duration of ischemia and the value of the maximum ST depression decreased by 46 and 43%, respectively.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Bronchitis, Chronic; Calcium Channel Blockers; Cardiovascular Agents; Diltiazem; Echocardiography; Electrocardiography; Electrocardiography, Ambulatory; Enalapril; Exercise Test; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Time Factors; Treatment Outcome

The Circadian Anti-ischemia Program in Europe (CAPE II) compared the efficacy of amlodipine and diltiazem (Adizem XL) and the combination of amlodipine/atenolol and diltiazem (Adizem XL)/isosorbide 5-mononitrate on exercise and ambulatory myocardial ischemia during regular therapy and after omission of medication.. The optimal medical therapy for ischemia suppression and the impact of irregular dosing using agents with different pharmacologic properties has not been established in patients with coronary disease.. Patients with > or = 4 ischemic episodes or > or = 20 min of ST segment depression on 72-h electrocardiogram were randomized to amlodipine 10 mg once daily or diltiazem (Adizem XL) 300 mg once daily in a 14-week double-blind randomized multicountry study. In the second phase, atenolol 100 mg was added to amlodipine and isosorbide 5-mononitrate 100 mg to diltiazem (Adizem XL). Ambulatory monitoring (72 h) and exercise testing were repeated after both phases, on treatment and after a 24-h drug-free interval.. Both monotherapy with amlodipine and diltiazem (Adizem XL) were effective on symptoms and ambulatory and exercise ischemia. Combination therapy reduced ischemia further, with amlodipine/atenolol superior to diltiazem (Adizem XL)/isosorbide 5-mononitrate. Amlodipine/atenolol was significantly superior during the drug-free interval with maintenance of ischemia reduction.. Amlodipine, with its intrinsically long half-life alone or together with beta-blocker, is likely to produce superior ischemia reduction in clinical practice when patients frequently forget to take medication or dose irregularly.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Amlodipine; Atenolol; Calcium Channel Blockers; Cardiovascular Agents; Coronary Disease; Diltiazem; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Electrocardiography; Exercise Test; Female; Humans; Isosorbide; Male; Middle Aged; Myocardial Ischemia

In patients with stable angina pectoris or silent myocardial ischemia, who had signs of ischemia in ECG during exercise, the Asymptomatic Cardiac Ischemia Pilot (ACIP) study compared 2 types of medication strategies (ischemia-guided and angina-guided) and a strategy of primary revascularization by PTCA or CABG. ACIP substantiated, after 2 years of observation, a clear advantage of the revascularization strategy compared to both drug strategies in terms of clinical effectiveness. This advantage is even more distinct in patients with very severe angiographic results.. This is a retrospective, incremental cost-effectiveness analysis from the perspective of the German third party payer (statutory sick funds) on the basis of the ACIP study.. The direct costs of the revascularization strategy after 2 years are about 2 to 3 times higher than those of the drug therapies. The incremental cost-effectiveness of the ischemia-guided strategy versus an angina-guided strategy is DM 2,600 per life-year saved. Furthermore, the cost-effectiveness of a revascularization strategy versus an angina guided therapy is DM 15,100 per life-year saved.. A primary revascularization strategy is cost-effective in patients with stable coronary artery disease with proven myocardial ischemia and positive angiographic signs.

Topics: Aged; Angina Pectoris; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Bypass; Coronary Disease; Cost-Benefit Analysis; Disease Management; Female; Germany; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Revascularization; Pilot Projects; Randomized Controlled Trials as Topic; Retrospective Studies; Single-Blind Method; Survival Analysis

Correction of the metabolic link of the natural course of ischemic heart disease (IHD) was found out to be a real reserve of enhancement of therapy efficiency in treating this condition. A total of 137 IHD patients were examined, presenting with functional class II-III exertional angina, their age ranging between 67 to 86 years. Kinds of metabolic complexes to be used in IHD treatment included amino acids, antioxidants, cofactors, energy-providing compounds that enhance efficiency of basic methods of IHD therapy. A positive therapeutic effect of metabolic correction treatments was evidenced by earlier dispelling of electrocardiographic signs of myocardial ischemia, higher tolerance to physical load, improvement in parameters characterizing cardio-hemodynamics.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Cardiovascular Agents; Drug Therapy, Combination; Energy Metabolism; Heart; Hemodynamics; Humans; Myocardial Ischemia; Myocardium

The authors made an analysis of results of examination of 41 patients with ischemic heart disease treated by the standard medicamentous therapy and when using different methods of photohemotherapy against its background. It was established that medicamentous therapy during 2 weeks failed to result in a substantial improvement of rheological properties of blood, while its combination with photohemotherapy could give a considerable positive effect coinciding with clinical improvement of the patient's state. Shorter terms are required to correct hemorheological indices when autotransfusions of photomodified blood are used.

Topics: Aged; Blood; Blood Transfusion, Autologous; Blood Viscosity; Cardiovascular Agents; Catheterization, Peripheral; Combined Modality Therapy; Drug Therapy, Combination; Female; Hemorheology; Humans; Male; Middle Aged; Myocardial Ischemia; Time Factors; Ultraviolet Therapy

The role of testosterone on the development of coronary artery disease in men is controversial. The evidence that men have a greater incidence of coronary artery disease than women of a similar age suggests a possible causal role of testosterone. Conversely, recent studies have shown that the hormone improves endothelium-dependent relaxation of coronary arteries in men. Accordingly, the aim of the present study was to evaluate the effect of acute administration of testosterone on exercise-induced myocardial ischemia in men.. After withdrawal of antianginal therapy, 14 men (mean age, 58+/-4 years) with coronary artery disease underwent 3 exercise tests according to the modified Bruce protocol on 3 different days (baseline and either testosterone or placebo given in a random order). The exercise tests were performed 30 minutes after administration of testosterone (2.5 mg IV in 5 minutes) or placebo. All patients showed at least 1-mm ST-segment depression during the baseline exercise test and after placebo, whereas only 10 patients had a positive exercise test after testosterone. Chest pain during exercise was reported by 12 patients during baseline and placebo exercise tests and by 8 patients after testosterone. Compared with placebo, testosterone increased time to 1-mm ST-segment depression (579+/-204 versus 471+/-210 seconds; P<0. 01) and total exercise time (631+/-180 versus 541+/-204 seconds; P<0. 01). Testosterone significantly increased heart rate at the onset of 1-mm ST-segment depression (135+/-12 versus 123+/-14 bpm; P<0.01) and at peak exercise (140+/-12 versus 132+/-12 bpm; P<0.01) and the rate-pressure product at the onset of 1-mm ST-segment depression (24 213+/-3750 versus 21 619+/-3542 mm Hgxbpm; P<0.05) and at peak exercise (26 746+/-3109 versus 22 527+/-5443 mm Hgxbpm; P<0.05).. Short-term administration of testosterone induces a beneficial effect on exercise-induced myocardial ischemia in men with coronary artery disease. This effect may be related to a direct coronary-relaxing effect.

Topics: Aged; Cardiovascular Agents; Coronary Disease; Electrocardiography; Exercise Test; Humans; Injections, Intravenous; Male; Middle Aged; Myocardial Ischemia; Testosterone

Topics: Biomarkers; Cardiovascular Agents; Diltiazem; Humans; Ischemic Preconditioning, Myocardial; Myocardial Ischemia; Perioperative Care; Troponin I

Topics: Angina Pectoris; Antioxidants; Cardiovascular Agents; Coenzymes; Cytoprotection; Female; Heart; Humans; Lipid Peroxidation; Male; Middle Aged; Myocardial Ischemia; Myocardium; Physical Exertion; Time Factors; Ubiquinone

Dilthiazem has been shown to exert a positive effect on haemodynamics in patients in different stages of heart failure. Reduction in postload under the influence of dilthiazem is a cardinal factor of improvement of intracardiac haemodynamics making for increase in cardiac output and regional blood flow.

Topics: Adult; Cardiovascular Agents; Diltiazem; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia

We hypothesized that among the patients enrolled in the Asymptomatic Cardiac Ischemia Pilot (ACIP) trial, those who reported angina either within the previous 6 weeks or experienced angina during ambulatory electrocardiographic (ECG) monitoring during activities of daily life or during stress testing would be more likely to experience an adverse cardiac event within a year than those who did not experience angina. Of the 558 patients enrolled in ACIP, 325 (58.2%) reported angina in the previous 6 weeks, 300 (53.8%) had stress-induced angina, and 63 (11.3%) reported angina during activities of daily life associated with ST-segment changes on the 48-hour ambulatory electrocardiogram. Some patients had > 1 of these angina symptoms and thus 8 angina status categories were identified. Adverse cardiac events were defined as death, nonfatal myocardial infarction (MI), or hospitalization for ischemic events, which included revascularization not specified by the ACIP protocol. One hundred and sixty-seven patients (29.9%) were asymptomatic (i.e., they never had angina) by our defined criteria. Three hundred ninety-one patients (70.1%) were symptomatic. Symptomatic patients had a higher incidence of death, MI, or hospitalization for ischemic events (15.3% symptomatic vs 7.8% asymptomatic, p = 0.016). History of angina within 6 weeks before randomization was predictive of death, MI, or hospitalization for ischemic event (p = 0.007). This finding was due to a large difference in the need for hospitalizations which would be expected to be driven by the presence of angina. By contrast, angina during ambulatory electrocardiogram or stress test was not predictive of an adverse cardiac event. The asymptomatic status of coronary disease patients who have objective documentation of ischemia is not uniformly defined and many different categories can be identified. In this population of patients with proven coronary artery disease and myocardial ischemia, a history of angina in the previous 6 weeks was a good predictor of an adverse event occurring in the next year.

Topics: Angina Pectoris; Cardiovascular Agents; Death, Sudden, Cardiac; Electrocardiography, Ambulatory; Follow-Up Studies; Hospitalization; Humans; Incidence; Life Tables; Myocardial Infarction; Myocardial Ischemia; Myocardial Revascularization; Pilot Projects; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Time Factors

To evaluate the perioperative effects of intravenous diltiazem infusion on left ventricular functions, hemodynamics and as an anti-ischemic and antiarrhythmic agent in patients undergoing coronary artery bypass grafting (CABG).. A double blind, randomised study was performed on 71 patients undergoing elective CABG. Infusion of diltiazem (0.1 mg/kg per h, n = 34) or nitroglycerin (1 microgram/kg per min, n = 37) was given for 24 h starting from onset of cardiopulmonary bypass. Holter monitoring, electrocardiogram and serum cardiac enzymes levels were used to diagnose myocardial ischemia. Myocardial function was assessed by perioperative transesophageal echocardiography.. The two groups did not differ with respect to preoperative and operative data. Diltiazem had no influence on hemodynamic parameters except for significant reduction in post operative heart rate and pulse pressure rate. Transient ischemic events (dilitiazem 10.2% versus nitroglycerin 33.3%, P = 0.15) and transient coronary spasm (diltiazem-6.8% versus nitroglycerin 25.9%, P = 0.15) were reduced in the diltiazem group as compared with the nitroglycerin group. The postoperative incidence of atrial fibrillation (diltiazem 3% versus nitroglycerin 22%, P = 0.03), supra ventricular tachycardia (diltiazem-3% versus nitroglycerin-22%, P = 0.03) and average ventricular premature contraction per h (diltiazem-40.2 +/- 10.2 versus nitroglycerin 53.8 +/- 12.3, P < 0.01) were significantly lower in the diltiazem group. Transesophageal echocardiography showed no significant difference in left ventricular functions and better preservation of left ventricular diastolic functions in post cardiopulmonary bypass period in diltiazem group. In addition mean deceleration time for the E wave on a 12 h post cardiopulmonary bypass period was significantly lower in the diltiazem group as compared with nitroglycerin (diltiazem 131 +/- 6 versus nitroglycerin 171 +/- 6, P < 0.01).. The present study demonstrates that diltiazem infusion provides superior anti-ischemic protection and control of supraventricular arrhythmias as compared to nitroglycerin and does not produce any negative inotropic effect, as demonstrated by transesophageal echocardiography.

Topics: Aged; Arrhythmias, Cardiac; Cardiovascular Agents; Coronary Artery Bypass; Diltiazem; Double-Blind Method; Female; Hemodynamics; Humans; Infusions, Intravenous; Intraoperative Care; Male; Middle Aged; Monitoring, Intraoperative; Myocardial Ischemia; Nitroglycerin; Vasodilator Agents

Lipid-lowering therapy reduces cardiac morbidity and mortality. Less is known about its potential anti-ischemic effect.. In a 2-year prospective randomized placebo-controlled study, the effect of pravastatin 40 mg on transient myocardial ischemia was assessed. Forty-eight-hour ambulatory ECGs with continuous ST-segment analysis were performed in 768 male patients with stable angina pectoris, documented coronary artery disease, and serum cholesterol between 4 and 8 mmol/L (155 and 310 mg/dL). During the trial, patients received routine antianginal treatment. In the patients randomized to pravastatin, transient myocardial ischemia was present at baseline in 28% and after treatment in 19%; in the placebo group, it was found in 20% and 23% of the patients, respectively (P = .021 for change in percentage between two treatment groups; odds ratio, 0.62; 95% CI, 0.41 to 0.93). Ischemic episodes decreased by 1.23 +/- 0.25 (SEM) episode with pravastatin and by 0.53 +/- 0.25 episode with placebo (P = .047). Under pravastatin, the duration of ischemia decreased from 80 +/- 12 minutes to 42 +/- 10 minutes (P = .017) and with placebo, from 60 +/- 13 minutes to 51 +/- 9 minutes (P = .56). The total ischemic burden decreased from 41 +/- 5 to 22 +/- 5 mm.min in the pravastatin group (P = .0058) and from 34 +/- 6 to 26 +/- 4 mm . min in the placebo group (P = .24). Adjusted for independent risk factors for the occurrence of ischemia, the effect of pravastatin on the reduction of risk for ischemia remained statistically significant (odds ratio, 0.45; 95% CI, 0.22 to 0.91; P = .026).. In men with documented coronary artery disease and optimal antianginal therapy, pravastatin reduces transient myocardial ischemia.

Topics: Angina Pectoris; Anticholesteremic Agents; Cardiovascular Agents; Cholesterol; Drug Therapy, Combination; Electrocardiography, Ambulatory; Humans; Male; Middle Aged; Myocardial Ischemia; Pravastatin; Prospective Studies

To examine the degree of success at maintaining patients randomized to epidural or general anesthesia for peripheral vascular surgery within predetermined blood pressure (BP) and heart rate (HR) limits. To investigate associations between such hemodynamic control and intraoperative myocardial ischemia and postoperative major cardiac morbidity.. Prospective randomized clinical trial.. University-affiliated hospital.. 100 patients undergoing elective lower extremity revascularization for atherosclerotic peripheral vascular disease.. Patients were randomized to receive either epidural anesthesia or general anesthesia. Blood pressure and HR limits were determined prior to randomization. Hemodynamic monitoring and management of anesthesia was standardized. Myocardial ischemia and major cardiac morbidity were diagnosed by a blinded cardiologist, based on continuous ambulatory ECG monitoring, cardiac enzymes, and 12 lead ECGs. Intraoperative BP and HR date were analyzed by investigators masked to the type of anesthesia given.. A greater percentage of patients randomized to general anesthesia had intraoperative BPs more above their limit (95% vs 72%, p = 0.002) and/or more rapid changes in HR (75% vs 48%, p = 0.008) or BP (100% vs 93%, p = 0.04) than those randomized to epidural anesthesia. Intraoperative ischemia and major cardiac morbidity were similar in the two anesthesia groups. Patients experiencing intraoperative ischemia, regardless of anesthetic type, more frequently had BPs greater than 10% above their upper limit (90% vs 60% p = 0.04) and/or more rapid HR changes (90% vs 58%, p = 0.03) compared with patients without ischemia. These vital sign abnormalities, however, were not necessarily temporally related to the ischemic episodes. Patients experiencing subsequent major cardiac morbidity were not different from other patients with respect to excursions out of BP on HR limits.. Prevention of elevated intraoperative BP and/on rapid changes in BP or HR may be more successful with epidural than with general anesthesia. Such vital sign abnormalities may occur more frequently in patients who have had intraoperative ischemia or are at risk for having it later in the procedure.

Topics: Aged; Anesthesia, Epidural; Anesthesia, General; Arteriosclerosis; Blood Pressure; Cardiovascular Agents; Elective Surgical Procedures; Electrocardiography, Ambulatory; Female; Heart Diseases; Heart Rate; Humans; Intraoperative Complications; Leg; Male; Middle Aged; Monitoring, Intraoperative; Myocardial Ischemia; Myocardium; Peripheral Vascular Diseases; Postoperative Complications; Prospective Studies; Risk Factors; Single-Blind Method

This pilot study demonstrated that (1) patients with CAD and asymptomatic cardiac ischemia can be randomized to medical or revascularization strategies using a complex and demanding protocol, (2) asymptomatic cardiac ischemia can be suppressed in 40-50% of patients with clinically advanced coronary disease with relatively low to moderate doses of medication titrated over a period of 12 weeks (3). Revascularization was the most effective of the treatment strategies studied in reducing ischemia. Any type of therapy, whether it be drugs or revascularization requiring repetitive monitoring with ambulatory ECG or other methods to detect ischemia over a long period of time, will escalate the cost of quality medical care for our patients. Thus, the health care costs implications and treatment of asymptomatic ischemia are enormous. But the apparent cost advantage of treating only symptoms, that is ignoring all ischemia, could disappear if treatment of ischemia reduces the risk of adverse events. The clinical question to be addressed in the future is what is necessary to reduce the cardiac-event rates of death and myocardial infarction in this group of patients? Will more aggressive drug therapy eliminate more ischemia and will therapy directed at the elimination of all detectable ischemia improved clinical outcome better than therapy directed to control angina only? These questions can only be answered by a large clinical trial. The results of such a trial will provide the basis and rationale for safe and effective therapy for patients with coronary disease and evidence of cardiac ischemia. Whatever the answer to this important medical and scientific question is, it will have tremendous economic implications.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Angina Pectoris; Angioplasty; Cardiovascular Agents; Combined Modality Therapy; Coronary Artery Bypass; Electrocardiography, Ambulatory; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Prognosis

This report from the Asymptomatic Cardiac Ischemia Pilot (ACIP) study examines differences in the magnitude of reduction of myocardial ischemia as determined by exercise treadmill testing in patients randomized to three different treatment strategies: angina-guided medical therapy, ischemia-guided medical therapy and coronary revascularization.. No prospective randomized clinical trials in patients with exercise electrocardiographic (ECG) abnormalities and asymptomatic cardiac ischemia on ambulatory ECG monitoring have compared the impact of different treatment strategies, including coronary revascularization, in terms of reducing myocardial ischemia.. The ACIP exercise protocol was used. Exercise variables measured included final exercise stage; presence of exercise-induced angina or ischemia; time to angina; time to 1-mm ST segment depression; number of exercise ECG leads with abnormalities; maximal depth of ST segment depression in any lead; sum of ST segment depression; ST/HR index; and rate-pressure product at time to angina, at time to 1-mm ST segment depression and at peak exertion.. Peak exercise time was increased by 0.5, 0.7 and 1.6 min in patients assigned to the angina-guided, ischemia-guided and coronary revascularization strategies, respectively, from the qualifying visit to the 12-week visit (p < 0.001). At the qualifying visit, the sum of exercise-induced ST segment depression was 9.4 +/- 5.0 (mean +/- SD), 9.6 +/- 4.7 and 9.9 +/- 5.5 mm (p = NS) in the three treatment strategies, respectively. At the 12-week visit, the sum of exercise-induced ST segment depression was 7.4 +/- 5.7, 6.8 +/- 5.3 and 5.6 +/- 5.6 mm (p = 0.02) in the three treatment strategies, respectively. Each treatment strategy resulted in a significant reduction in all exercise-induced variables of myocardial ischemia measured at 12 weeks.. Coronary revascularization significantly reduced the extent and frequency of exercise-induced myocardial ischemia compared with either medical strategy. The prognostic impact of these observations should be evaluated in a large-scale multicenter clinical trial.

Topics: Analysis of Variance; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Combined Modality Therapy; Coronary Artery Bypass; Drug Therapy, Combination; Electrocardiography, Ambulatory; Exercise Test; Female; Humans; Male; Myocardial Ischemia; Pilot Projects; Prospective Studies; Remission Induction; Rest; Time Factors; Treatment Outcome

This report discusses the outcome at 1 year in patients in the Asymptomatic Cardiac Ischemia Pilot (ACIP) study.. Comparative efficacy of medical therapy versus revascularization in treatment of asymptomatic ischemia is unknown. The ACIP study assessed the ability of three treatment strategies to suppress ambulatory electrocardiographic (ECG) ischemia to determine whether a large-scale trial studying the impact of these strategies on clinical outcomes was feasible.. Five hundred fifty-eight patients with coronary anatomy amenable to revascularization, at least one episode of asymptomatic ischemia on the 48-h ambulatory ECG and ischemia on treadmill exercise testing were randomized to one of three treatment strategies: 1) medication to suppress angina (angina-guided strategy, n = 183); 2) medication to suppress both angina and ambulatory ECG ischemia (ischemia-guided strategy, n = 183); or 3) revascularization strategy (angioplasty or bypass surgery, n = 192). Medication was titrated atenolol-nifedipine or diltiazem-isosorbide dinitrate.. The revascularization group received less medication and had less ischemia on serial ambulatory ECG recordings and exercise testing than those assigned to the medical strategies. The ischemia-guided group received more medication but had suppression of ischemia similar to the angina-guided group. At 1 year, the mortality rate was 4.4% in the angina-guided group (8 of 183), 1.6% in the ischemia-guided group (3 of 183) and 0% in the revascularization group (overall, p = 0.004; angina-guided vs. revascularization, p = 0.003; other pairwise comparisons, p = NS). Frequency of myocardial infarction, unstable angina, stroke and congestive heart failure was not significantly different among the three strategies. The revascularization group had significantly fewer hospital admissions and nonprotocol revascularizations at 1 year. The incidence of death, myocardial infarction, nonprotocol revascularization or hospital admissions at 1 year was 32% with the angina-guided medical strategy, 31% with the ischemia-guided medical strategy and 18% with the revascularization strategy (p = 0.003).. After 1 year, revascularization was superior to both angina-guided and ischemia-guided medical strategies in suppressing asymptomatic ischemia and was associated with better outcome. These findings require confirmation by a larger scale trial.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Combined Modality Therapy; Coronary Artery Bypass; Drug Therapy, Combination; Electrocardiography, Ambulatory; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Pilot Projects; Prospective Studies; Remission Induction; Time Factors; Treatment Outcome

The Asymptomatic Cardiac Ischemia Pilot (ACIP) study showed that revascularization is more effective than medical therapy in suppressing cardiac ischemia at 12 weeks. This report compares the relative efficacy of coronary angioplasty or coronary artery bypass graft surgery in suppressing ambulatory electrocardiographic (ECG) and treadmill exercise cardiac ischemia between 2 and 3 months after revascularization in the ACIP study.. Previous studies have shown that coronary angioplasty and bypass surgery relieve angina early after the procedure in a high proportion of selected patients. However, alleviation of ischemia on the ambulatory ECG and treadmill exercise test have not been adequately studied prospectively after revascularization.. In patients randomly assigned to revascularization in the ACIP study, the choice of coronary angioplasty or bypass surgery was made by the clinical unit staff and the patient.. Patients assigned to bypass surgery (n = 78) had more severe coronary disease (p = 0.001) and more ischemic episodes (p = 0.01) at baseline than those assigned to angioplasty (n = 92). Ambulatory ECG ischemia was no longer present 8 weeks after revascularization (12 weeks after enrollment) in 70% of the bypass surgery group versus 46% of the angioplasty group (p = 0.002). ST segment depression on the exercise ECG was no longer present in 46% of the bypass surgery group versus 23% of the angioplasty group (p = 0.005). Total exercise time in minutes on the treadmill exercise test increased by 2.4 min after bypass surgery and by 1.4 min after angioplasty (p = 0.02). Only 10% of the bypass surgery group versus 32% of the angioplasty group still reported angina in the 4 weeks before the 12-week visit (p = 0.001).. Angina and ambulatory ECG ischemia are relieved in a high proportion of patients early after revascularization. However, ischemia can still be induced on the treadmill exercise test, albeit at higher levels of exercise, in many patients. Bypass surgery was superior to coronary angioplasty in suppressing cardiac ischemia despite the finding that patients who underwent bypass surgery had more severe coronary artery disease.

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Combined Modality Therapy; Coronary Artery Bypass; Drug Therapy, Combination; Electrocardiography, Ambulatory; Exercise Test; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Ischemia; Pilot Projects; Prospective Studies; Recurrence; Remission Induction; Time Factors; Treatment Outcome

Over an eight year period (1985-1993), we treated 424 patients with various forms of cardiovascular disease by adding coenzyme Q10 (CoQ10) to their medical regimens. Doses of CoQ10 ranged from 75 to 600 mg/day by mouth (average 242 mg). Treatment was primarily guided by the patient's clinical response. In many instances, CoQ10 levels were employed with the aim of producing a whole blood level greater than or equal to 2.10 micrograms/ml (average 2.92 micrograms/ml, n = 297). Patients were followed for an average of 17.8 months, with a total accumulation of 632 patient years. Eleven patients were omitted from this study: 10 due to non-compliance and one who experienced nausea. Eighteen deaths occurred during the study period with 10 attributable to cardiac causes. Patients were divided into six diagnostic categories: ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM), primary diastolic dysfunction (PDD), hypertension (HTN), mitral valve prolapse (MVP) and valvular heart disease (VHD). For the entire group and for each diagnostic category, we evaluated clinical response according to the New York Heart Association (NYHA) functional scale, and found significant improvement. Of 424 patients, 58 per cent improved by one NYHA class, 28% by two classes and 1.2% by three classes. A statistically significant improvement in myocardial function was documented using the following echocardiographic parameters: left ventricular wall thickness, mitral valve inflow slope and fractional shortening. Before treatment with CoQ10, most patients were taking from one to five cardiac medications. During this study, overall medication requirements dropped considerably: 43% stopped between one and three drugs. Only 6% of the patients required the addition of one drug. No apparent side effects from CoQ10 treatment were noted other than a single case of transient nausea. In conclusion, CoQ10 is a safe and effective adjunctive treatment for a broad range of cardiovascular diseases, producing gratifying clinical responses while easing the medical and financial burden of multidrug therapy.

Topics: Cardiomyopathy, Dilated; Cardiovascular Agents; Cardiovascular Diseases; Coenzymes; Diastole; Drug Therapy, Combination; Echocardiography; Female; Follow-Up Studies; Heart Function Tests; Heart Valve Diseases; Humans; Hypertension; Male; Middle Aged; Mitral Valve Prolapse; Myocardial Ischemia; Treatment Outcome; Ubiquinone

Prostaglandins and prostacyclin are potent vasodilators with marked hemodynamic effects, i.e., both improve cardiac function and possibly cause myocardial ischemia. In order to assess the stable prostacyclin analogon taprostene (T) we first performed an open preliminary study with increasing T-doses (6.5-50 ng/kg/min) and, secondly a double-blind crossover study versus placebo to investigate its influence on ischemic ST-segment depression during exercise stress testing under continuous T-infusions of 25 ng/kg/min (in one case 12.5 ng/kg/min). Eleven of 12 normotensive male patients (age 40 to 60, mean 52.8 +/- 8.4 years) suffering from angiographically proven coronary heart disease and stable angina pectoris completed the study. T was well tolerated, even under increasing doses, and blood pressure and the ECG parameters did not change. The double-blind study revealed no variation in the extent of ischemic ST-segment depression when compared to placebo, and all other ECG parameters as well as the blood pressure remained unaffected. Thus, myocardial ischemia cannot be ruled out completely under T, but earlier clinical findings may be confirmed characterizing T as a marked cytoprotective agent and, to a less degree, as a potent vasodilator.

Topics: Adult; Aged; Cardiovascular Agents; Coronary Circulation; Coronary Disease; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Epoprostenol; Exercise Test; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia

Myocardial ischemia-reperfusion injury leads to aggravated cardiac remodeling and heart failure. After myocardial infarction (MI), angiogenesis plays a vital role in the repair and regeneration of tissue. The purpose of the current study was to determine the effect of Tanshinone IIA (Tan IIA) on angiogenesis and elucidate its related mechanism.. The C57BL/6 mice MI model was established to evaluate the therapeutic effect of Tan IIA in vivo. MicroRNA (miRNA) microarray and bioinformatics analysis were performed to determine the differential expressions of miRNAs after Tan IIA administration. Cell proliferation, migration, and angiogenesis capacity were detected by EdU, Transwell, and Tube formation assay in vitro, respectively. The relationship between miR-499-5p (miR-499) and paired phosphate and tension homolog deleted on chromosome ten (PTEN) was confirmed by using a Dual-luciferase reporter assay.. Our results showed that Tan IIA administration improved cardiac function after MI by activating angiogenesis. Further miRNA microarray and bioinformatics analysis revealed that miR-499 was significantly down-regulated, while PTEN was remarkably upregulated after Tan IIA administration post-MI. In addition, we found that miR-499 knock-down effectively promotes cell proliferation, migration, and tube formation ability of HUVECs. Dual-luciferase reporter assay demonstrated that PTEN contains a direct binding site for miR-499-5p.. Tan IIA improves cardiac function post-MI by inducing angiogenesis. In terms of the mechanism, Tan IIA promotes therapeutic angiogenesis by regulating miR-499-5p/PTEN signaling pathway.

Topics: Abietanes; Animals; Cardiovascular Agents; Disease Models, Animal; Mice; Mice, Inbred C57BL; MicroRNAs; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Neovascularization, Pathologic; Neovascularization, Physiologic; PTEN Phosphohydrolase

Myocardial autophagy has been recognized as an important factor in heart failure. It is not known whether changes in ventricular geometry by left ventriculoplasty influence autophagy in ischemic cardiomyopathy. We hypothesized that myocardial autophagy plays an important role in left ventricular (LV) redilation after ventriculoplasty.. Four weeks after ligation of the left anterior descending artery, ventriculoplasty or sham operation was performed. The animals were euthanized at 2 days (early) or 28 days (late) after the second operation. Ventricular autophagy was evaluated by protein expression of microtubule-associated protein light chain 3 II, an autophagosome marker. Cardiomyocyte area was assessed by histologic examination. LV function was evaluated by echocardiography. To examine the implications of autophagy, an autophagy inhibitor (3-methyladenine) was injected intraperitoneally for 3 weeks before sacrifice.. The LV was reduced in size early and redilated late after ventriculoplasty. LV systolic function was improved early and later worsened after ventriculoplasty. Light chain 3 II expression decreased early after ventriculoplasty and increased in the late period. Myocyte area increased from the early to late stage after ventriculoplasty. Autophagic inhibition exaggerated the increased myocyte hypertrophy and LV redilation.. In a rat model of myocardial infarction, autophagy decreased early after ventriculoplasty and increased again during LV redilation. These results provide new insights into the mechanism underlying the late failure of ventriculoplasty.

Topics: Adenine; Animals; Autophagy; Autophagy-Related Proteins; Cardiomyopathy, Dilated; Cardiomyoplasty; Cardiovascular Agents; Echocardiography; Microtubule-Associated Proteins; Myocardial Ischemia; Myocytes, Cardiac; Rats; Recurrence; Ventricular Function, Left; Ventricular Remodeling

Topics: Animals; Biological Availability; Caco-2 Cells; Cardiovascular Agents; Diffusion; Disease Models, Animal; Humans; Hydrogen Bonding; Isoflavones; Isoproterenol; Male; Myocardial Ischemia; Nanoparticles; Particle Size; Rats; Rats, Sprague-Dawley; Solubility

Recently, 12 randomized clinical trials (RCTs) have demonstrated the efficacy of novel therapies for mainly secondary prevention of atherosclerotic cardiovascular disease. However, given the potential overlapping eligibility of the RCTs, along with the cost of the new therapies, there are uncertainty and questions about implementing these RCT findings in real-world clinical practice.. To determine the eligibility and preventive potential for these new preventive therapies in a contemporary population.. This population-based contemporary cohort study included 6292 patients with known ischemic heart disease (IHD) and 2277 with a previous myocardial infarction (MI) enrolled between November 2003 and February 2015. Analyses were performed in the Copenhagen General Population Study with a mean (SD) of 7.7 (3.5) years of follow-up. The data were analyzed between January and October 2019.. We determined the drug eligibility and evidence-based potential for preventing major cardiovascular events of the 12 cardiovascular drugs tested in the following recent RCTs: IMPROVE-IT, PEGASUS, EMPA-REG, LEADER, SUSTAIN-6, FOURIER, CANVAS, REVEAL, CANTOS, COMPASS, ODYSSEY-OUTCOMES, and REDUCE-IT. The analyses were performed in patients with known IHD or with a previous MI at baseline.. Of 6292 participants, 3861 (61%) were men and the mean (interquartile range) age was 69 (62-76) years. In patients with IHD or MI at baseline, eligibility for 1 or more new medications was 80% (n = 5036) and 99% (n = 2273), respectively, by meeting RCT enrollment criteria. Dividing the new therapies into 4 drug classes (lipid-modifying, antithrombotic, anti-inflammatory, and antidiabetic drugs), 2594 and 1834 patients with IHD or MI (41% and 81%, respectively) were eligible for 2 or more drug classes simultaneously. The 5-year estimated percentage of major cardiovascular events that could be prevented for each new therapy was 1% to 20% in patients with IHD or MI at baseline.. Most patients with known IHD or previous MI are eligible for additional new secondary prevention therapies. This raises questions for the cardiovascular community and health care authorities about access to these potentially expensive therapies, including strategies for prioritizing their use.

Topics: Aged; Atherosclerosis; Cardiovascular Agents; Cohort Studies; Evidence-Based Pharmacy Practice; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Secondary Prevention

Topics: Adult; Aged; Angina Pectoris; Cardiovascular Agents; Coronary Circulation; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Middle Aged; Myocardial Ischemia; Myocardial Perfusion Imaging; Prospective Studies; Recovery of Function; Risk Assessment; Risk Factors; Sex Factors; Surveys and Questionnaires; Time Factors; Treatment Outcome; United States; Ventricular Function, Left; Ventricular Remodeling

Orthostatic hypotension (OH) is a disabling condition accompanying several diseases. It has increased morbidity and mortality, and limited chances of treatment. We report a case of a patient with stable ischemic heart disease and severe OH unresponsive to usual care. A baseline 75° head-up tilt test (HUT) was positive for symptomatic OH, i.e. pre-syncope with a systolic arterial pressure drop of 35 mmHg. On top of optimal treatment, ivabradine was started. Symptoms improved within 24 hours. At a repeated HUT, the patient could tolerate the up-right position up to 25 minutes. He was able to undergo an individualized training program with further amelioration of quality of life. Thereafter, titration of ACE inhibitors became possible. Lasting benefits were present at a 6-month follow-up. To our knowledge, this is the first reported case of successful use of ivabradine to integrate cardiac rehabilitation for management of a highly disabling OH.. L’ipotensione ortostatica è una condizione disabilitante che si accompagna a diverse patologie, è di sempre più frequente riscontro, aumenta la mortalità e ha limitate opzioni terapeutiche. Il caso clinico riportato è quello di un paziente con cardiopatia ischemica stabile e grave ipotensione ortostatica, nonostante l’adozione di tutte le terapie standard. A un primo tilt test a 75° eseguito in condizioni basali, il paziente ha sviluppato ipotensione ortostatica grave (riduzione della pressione sistolica di 35 mmHg) con pre-sincope. Alla terapia in atto è stata aggiunta ivabradina 5 mg due volte al giorno. Nelle 24 ore successive si è assistito a un netto miglioramento soggettivo. È stato quindi ripetuto il tilt test di durata 25 minuti, che il paziente ha ben tollerato. In corso di proseguimento della terapia con ivabradina il paziente è stato in grado di completare un programma di allenamento fisico individualizzato che ha ulteriormente migliorato la sua qualità di vita ed ha anche permesso di titolare correttamente la terapia con ACE inibitori. A una visita di controllo dopo 6 mesi, il paziente riferiva assenza di episodi sincopali o pre-sincopali. In conclusione, questo è il primo caso di utilizzo efficace dell’ivabradina, in associazione con un programma di riabilitazione cardiologica, per il trattamento dell’ipotensione ortostatica grave in un paziente con cardiopatia ischemica.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiac Rehabilitation; Cardiovascular Agents; Humans; Hypotension, Orthostatic; Ivabradine; Male; Myocardial Ischemia; Quality of Life; Standing Position; Tilt-Table Test; Time Factors

Topics: Aged; Bronchopulmonary Sequestration; Cardiovascular Agents; Conservative Treatment; Coronary Vessel Anomalies; Female; Humans; Multimodal Imaging; Myocardial Ischemia; Pulmonary Artery; Treatment Outcome

Optimal medical therapy is endorsed by national guidelines in the management of ischemic heart disease; however, few studies have examined its long-term utilization following percutaneous coronary intervention (PCI) and association with clinical outcomes. We sought to assess longitudinal trends in medical therapy use after PCI and its prognostic significance.. From the Veteran Affairs Clinical Assessment, Reporting, and Tracking System Program, we retrospectively identified 57 900 Veteran's Affairs patients undergoing PCI from January 2005 to May 2014. Using prescription fill dates, the utilization of 4 classes of medical therapy including statins, β-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, P2Y12 inhibitors, and their composites were assessed at discharge, 6 months, 1, 3, and 5 years post-PCI. Multivariable Cox regression models were developed to assess the association between medical therapy status and major adverse cardiovascular events, defined as all-cause mortality, rehospitalization for myocardial infarction, rehospitalization for stroke, or repeat revascularization. At discharge following PCI, 58.3% of patients received all 4 classes of medical therapy. Utilization of statins, β-blockers, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers decreased from 89%, 84.9%, and 72.2% on discharge, respectively, to 72.7%, 67.9%, and 57.9% at 5 years. Prescription refills of P2Y12 inhibitors declined from 96.5% on discharge to 28.3% at 5 years, driven by a large decline in P2Y12 inhibitor use after 1 year. Use of each class of medical therapy, and its composite use, was associated with a significant reduction in major adverse cardiovascular events at 5 years, with the largest effect size seen by the use of statins (HR, 0.77; 95% CI, 0.75-0.79;. Consistent declines in medical therapy use following PCI were observed over time, which is associated with worse outcomes. Further efforts are needed to promote long-term adherence to secondary prevention therapies after revascularization.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Databases, Factual; Disease Progression; Drug Utilization; Female; Guideline Adherence; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Practice Guidelines as Topic; Practice Patterns, Physicians'; Purinergic P2Y Receptor Antagonists; Recurrence; Retrospective Studies; Risk Assessment; Risk Factors; Secondary Prevention; Time Factors; Treatment Outcome; United States; United States Department of Veterans Affairs; Veterans Health Services

Heart failure (HF) with recovered ejection fraction (EF) is emerging as a different HF subtype. There is little information about his clinical profile in hospitals that are not a reference.. We analysed characteristics and prognosis in patients with recovered HF followed prospectively in the HF Unit of a non-tertiary hospital.. A total of 431 patients with HF with reduced EF were followed (median 50 months, 79.3% males, mean age 70.3±12.2years). Of the patients, 26.9% (N 116) recovered EF, mainly in the first year of follow-up (76.7%). Compared with patients that did not recovered EF in the follow-up, they were younger, rate of ischemic origin of cardiomyopathy was less frequent and presented less comorbidity. Mortality was lower in patients with recovered HF (survival median of 85.2±2.1 vs. 74.2±1.9 months [log-rank χ. HF with recovered EF is a frequent phenomenon. It has a more favourable clinical course, prognosis and basal characteristics than HF with persistent reduced EF. Further studies are needed to identify natural history and optimal medications for HF-recovered patients.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Cause of Death; Comorbidity; Female; Follow-Up Studies; Heart Failure; Heart Transplantation; Hospitals, General; Humans; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Myocardial Ischemia; Odds Ratio; Prognosis; Proportional Hazards Models; Prospective Studies; Spain; Stroke Volume; Survival Analysis

Topics: Adrenergic Agents; Animals; Anxiety; Cardiovascular Agents; Clonidine; Disease Models, Animal; Disease Susceptibility; Heart; Male; Myocardial Ischemia; Myocardium; Propranolol; Random Allocation; Rats, Sprague-Dawley; Stress Disorders, Post-Traumatic; Sympathetic Nervous System; Treatment Failure

Background The severity of coronary artery disease (CAD) and of ischemia are evaluated to guide therapy, but their relative prognostic importance remains uncertain. Accordingly, we sought to clarify their association with long-term survival in the COURAGE trial (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation). Methods and Results Survival data from after the original trial period ended was obtained at 15 Veterans Affairs sites and 13 of 18 United States non-Veterans Affairs sites. Date of death was obtained from the Veterans Affairs system-wide Corporate Data Warehouse and the National Death Index. Of the original 2287 patients in COURAGE, 1370 (60%) had both stress perfusion imaging and quantitative coronary angiography available, with extended survival evaluated in 767 subjects. Survival was calculated by the Kaplan-Meier method, and a Cox proportional-hazards model adjusted for baseline differences. There were 369 all-cause deaths during a median follow-up of 7.9 years (range, 0-15 years). The number of coronary arteries diseased predicted survival (HR, 1.25; 95% CI, 1.09-1.43), whereas severity of ischemia did not (HR, 0.99; 95% CI, 0.80-1.22). Percutaneous coronary intervention did not offer a survival advantage over optimal medical therapy (HR, 0.95; 95% CI, 0.77-1.16) and there was no interaction between therapeutic strategy and number of coronary arteries diseased or severity of ischemia. In fully adjusted models, the number of coronary arteries diseased was not associated with increased mortality. Conclusions In univariate analysis, the number of coronary arteries diseased predicted long-term mortality, but severity of ischemia did not. Adjusted for baseline variables, neither assessment approach predicted mortality. Overall, there was no survival benefit from percutaneous coronary intervention in any subset defined by either angiographic or ischemic severity. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00007657.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Perfusion Imaging; Percutaneous Coronary Intervention; Predictive Value of Tests; Prognosis; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Tomography, Emission-Computed, Single-Photon; United States; United States Department of Veterans Affairs

We investigated the influence of the extent of viability using low dose dobutamine wall motion score index (WMS) on the survival benefit of surgical revascularization (CABG) versus medical therapy. In the STICH trial, viability assessment was not helpful in determining the benefit of CABG. However, the extent of viable myocardium with contractile function was not assessed in the trial. Dobutamine echocardiography was performed in 250 patients with ischemic left ventricular dysfunction (125-medically treated, 125-CABG). The mean ejection fraction (EF) was 32% in both groups. WMS during low dose dobutamine infusion was used to classify patients into groups with extensive (WMS < 2.00), intermediate (WMS 2.00-2.49), and limited (WMS ≥ 2.50) viability. Survival free of cardiac death was assessed at 2 years and for the complete duration of follow-up. There were 44 (35.2%) and 67 (53.6%) cardiac deaths in the revascularized and medically treated patients respectively (follow-up of 5.7 ± 5.8 years). Revascularized and medically treated patients with extensive viability had similar 2-year survival (p = 0.567) but revascularized patients had improved long-term survival (p = 0.0001). In those with intermediate viability, revascularization improved both 2 year (p = 0.014) and long-term survival (p = 0.0001). In patients with limited viability, 2-year survival was worse in revascularized patients (p = 0.04) and long-term survival was similar (p = 0 .25) in revascularized and medically treated groups. Patients with extensive and intermediate amounts of viability have improved survival with CABG but those with limited viability have poorer short-term outcome and no long-term benefit.

Topics: Aged; Cardiomyopathies; Cardiotonic Agents; Cardiovascular Agents; Clinical Decision-Making; Coronary Artery Bypass; Dobutamine; Echocardiography, Stress; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardium; Patient Selection; Predictive Value of Tests; Recovery of Function; Retrospective Studies; Risk Factors; Stroke Volume; Time Factors; Tissue Survival; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Successful chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can markedly reduce angina symptom burden, but many patients often remain on multiple antianginal medications (AAMs) after the procedure. It is unclear when, or if, AAMs can be de-escalated to prevent adverse effects or limit polypharmacy. We examined the association of de-escalation of AAMs after CTO PCI with long-term health status.. In a 12-center registry of consecutive CTO PCI patients, health status was assessed at 6 months after successful CTO PCI with the Seattle Angina Questionnaire and the Rose Dyspnea Scale. Among patients with technical CTO PCI success, we examined the association of AAM de-escalation with 6-month health status using multivariable models adjusting for revascularization completeness and predicted risk of post-PCI angina (using a validated risk model). We also examined predictors and variability of AAMs de-escalation.. Of 669 patients with technical success of CTO PCI, AAMs were de-escalated in 276 (35.9%) patients at 1 month. Patients with AAM de-escalation reported similar angina and dyspnea rates at 6 months compared with those whose AAMs were reduced (any angina: 22.5% vs 20%, P = .43; any dyspnea: 51.8% vs 50.1%, P = .40). In a multivariable model adjusting for complete revascularization and predicted risk of post-PCI angina, de-escalation of AAMs at 1 month was not associated with an increased risk of angina, dyspnea, or worse health status at 6 months.. Among patients with successful CTO PCI, de-escalation of AAMs occurred in about one-third of patients at 1 month and was not associated with worse long-term health status.

Topics: Aged; Angina Pectoris; Calcium Channel Blockers; Cardiovascular Agents; Chi-Square Distribution; Chronic Disease; Coronary Occlusion; Dyspnea; Female; Health Status; Health Surveys; Humans; Logistic Models; Male; Myocardial Ischemia; Nitro Compounds; Percutaneous Coronary Intervention; Prospective Studies; Quality of Life; Ranolazine; Registries; Time Factors

To compare clinical outcomes of patients treated with overlapping versus non-overlapping Absorb BVS.. Limited data are available on the clinical impact of stent overlap with the Absorb BVS bioresorbable stent.. We compared outcomes of patients receiving overlapping or non-overlapping Absorb BVS in the multicenter prospective RAI Registry.. Out of 1,505 consecutive patients treated with Absorb BVS, 1,384 were eligible for this analysis. Of these, 377 (27%) were in the overlap group, and 1,007 (73%) in the non-overlap group. The most frequent overlap configuration was the marker-to-marker type (48%), followed by marker-over-marker (46%) and marker-inside-marker (6%) types. Patients of the overlap group had higher prevalence of multivessel disease and higher SYNTAX score, and required more frequently the use of intravascular imaging. At a median follow-up of 368 days, no difference was observed between overlap and non-overlap groups in terms of a device-related composite endpoint (cardiac death, TV-MI, ID-TLR) (5.8% vs. 4.1%, P = 0.20) or of a patient-related composite endpoint (any death, any MI, any revascularization) (15.4% vs. 12.5%, P = 0.18). Cardiac death (1.0% vs. 1.3%, P = 0.54), MI (4.5% vs. 3.6%, P = 0.51), TVR (4.5% vs. 3.6%, P = 0.51) and stent thrombosis (1.1 vs. 1.5%, P = 1.00) were also comparable between groups. When assessing outcomes of the overlap population according to overlap configurations used, no difference was observed in terms of the device- or patient-related composite endpoints.. Outcomes of patients with or without overlapping BVS were comparable at mid-term follow-up despite higher angiographic complexity of the overlap subset. © 2017 Wiley Periodicals, Inc.

Topics: Absorbable Implants; Aged; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Everolimus; Female; Humans; Italy; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Prospective Studies; Prosthesis Design; Recurrence; Registries; Risk Factors; Time Factors; Tomography, Optical Coherence; Treatment Outcome; Ultrasonography, Interventional

The impact of atrial fibrillation (AF) on the prognosis of heart failure with preserved ejection fraction (HFpEF) is still the subject of debate. We analysed the influence of AF on the prognosis on mortality and readmission in patients with HFpEF.. Prospective observational study in 1,971 patients with HFpEF, who were admitted for acute heart failure. Patients were divided into 2 groups according to the presence or absence of AF. We analysed mortality, readmissions and combined mortality/readmissions at one year follow-up.. A total of 1,177 (59%) patients had AF, mean age 80.3 (7.8) years and 1,233 (63%) were women. Patients with HFpEF and AF were older, female, greater valvular aetiology and lower comorbidity measured by the Charlson index. At the one year follow-up, 430 (22%) patients had died and 840 (43%) had been readmitted. In the 2 groups analysed, there was no difference in all-cause mortality (22 vs. 21%; P=.739, AF vs. no-AF, respectively) or cardiovascular causes (9.6 vs. 8.2%; P=.739, AF vs. no-AF, respectively). In the multivariable analysis, factors associated with higher mortality were: age, male, valvular aetiology, uric acid, and comorbidity. In the analysis of the subgroup with HFpEF with AF, the presence of chronic AF compared to de novo AF was associated with higher mortality (HR 1,716; 95% CI 1,099-2,681; P=.018).. In patients with HFpEF, the presence of AF is frequent. During the one-year follow-up, the presence of AF does not influence mortality or readmissions in patients with HFpEF.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cardiovascular Agents; Cause of Death; Comorbidity; Female; Heart Failure; Heart Valve Diseases; Humans; Hypertension; Male; Myocardial Ischemia; Patient Readmission; Prospective Studies; Stroke Volume

Takayasu arteritis (TA), a systemic vasculitis typically occurring in female patients aged ≤40, can affect coronary arteries and cause ischemic heart disease (IHD). In this study, we investigated the prevalence of TA in young women presenting with IHD in the Emergency Department.. We evaluated hospital records of 158,860 consecutive female patients aged <40, who accessed the Emergency Department of our institution over 8 consecutive years (2007-2015). The prevalence of different etiologies of IHD was determined. Diagnosis of TA was established based on the 1990 ACR criteria.. Overall, 1950 women aged <40 presented to the Emergency Department with chest pain, dyspnea, palpitations, angina, heart failure, or cardiac arrest; 40 had acute IHD. The etiology was 'classic' atherosclerosis in 24 cases (60%), TA in 4 cases (10%), vasospasm and sympathomimetic drug abuse in 3 cases each (7.5%), coronary artery dissection and microvascular angina in 2 cases each (5%), Takotsubo and radiation-induced cardiomyopathy in 1 case each (2.5%).. Although a diagnosis of TA is likely to be overlooked, TA is not infrequent in younger females presenting with acute IHD, a finding relevant to the diagnosis and management of these patients.

Topics: Acute Disease; Adult; Cardiovascular Agents; Chest Pain; Emergency Medical Services; Female; Humans; Myocardial Ischemia; Prevalence; Takayasu Arteritis

The purpose of this study is to revisit cases rated as "inappropriate" in the 2012 appropriate use criteria (AUC) using the 2017 AUC.. AUC for coronary revascularization in patients with stable ischemic heart disease (SIHD) were released in January 2017. Earlier 2012 AUC identified a relatively high percentage of New York State patients for whom percutaneous coronary intervention (PCI) was rated as "inappropriate" versus optimal medical therapy alone.. New York State's PCI registry was used to rate inappropriateness of patients undergoing PCI in 2014 using the 2012 and 2017 AUC, and to examine patient characteristics for patients rated differently.. A total of 911 of 9,261 (9.8%) patients who underwent PCI in New York State in 2014 with SIHD without prior coronary artery bypass grafting were rated as "inappropriate" using the 2012 AUC, but only 171 (1.8%) patients were rated as "rarely appropriate" ("inappropriate" in 2012 AUC terminology) using the 2017 AUC. A total of 26% of all 8,407 patients undergoing PCI in New York State with 1- to 2-vessel SIHD were without high-risk findings on noninvasive testing and were either asymptomatic or without antianginal therapy. No current or past randomized controlled trials have focused on these patients.. The percentage of 2014 New York State PCI patients with SIHD who are rated "rarely appropriate" has decreased substantially using 2017 AUC in comparison with the older 2012 AUC. However, for many low-risk patients undergoing the procedure, the relative benefits of optimal medical therapy with and without PCI are unknown. Randomized controlled trials are needed to study these groups.

Topics: Cardiovascular Agents; Clinical Decision-Making; Guideline Adherence; Humans; Myocardial Ischemia; New York; Patient Selection; Percutaneous Coronary Intervention; Practice Guidelines as Topic; Practice Patterns, Physicians'; Process Assessment, Health Care; Registries; Risk Assessment; Risk Factors; Time Factors

Topics: Cardiac Catheterization; Cardiovascular Agents; Comparative Effectiveness Research; Endpoint Determination; Humans; Myocardial Ischemia; Randomized Controlled Trials as Topic; Research Design; Time Factors; Treatment Outcome

Ischemic heart disease (IHD) is associated with a shockable rhythm in out-of-hospital cardiac arrest (OHCA). However, the impact of IHD severity on first recorded rhythm is unknown. We hypothesized that the strength of the association between IHD and shockable rhythm increases with increasing IHD severity.. OHCA patients were identified in the Danish Cardiac Arrest Registry (2001-2014). Population-based registries were used to identify chronic diseases, drug prescriptions and cardiac procedures such as coronary angiography (CAG), percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). Severity of IHD was categorized as 1) No diagnosis of IHD, 2) IHD without previous CAG, PCI or CABG, 3) IHD with CAG, 4) IHD with PCI, and 5) IHD with CABG. Adjusted odds ratios (ORs) for a shockable rhythm was computed using multivariable logistic regression.. Of 34,749 patients with OHCA, 6325 (18.2%) patients had a diagnosis of IHD. The prevalence of a shockable rhythm was higher for patients with a previous diagnosis of IHD (25.6%) and for those with previous CAG (33.3%), PCI (36.4%) or CABG (34.0%) when compared to patients without IHD (21.2%). IHD was associated with shockable rhythm (OR = 1.69, 95%CI 1.55-1.85) when compared to patients without IHD. The association with shockable rhythm was higher for patients with a history of CAG (OR = 1.92, 95%CI 1.67-2.20) and PCI (OR = 1.93, 95%CI 1.67-2.23), but similar in patients with CABG (OR = 1.69, 95%CI 1.37-2.10).. IHD was associated with a shockable rhythm, with a moderate increase in the association in patients with a CAG or PCI procedure.

Topics: Aged; Cardiovascular Agents; Coronary Angiography; Denmark; Electric Countershock; Emergency Medical Services; Female; Heart Rate; Humans; Male; Middle Aged; Myocardial Ischemia; Out-of-Hospital Cardiac Arrest; Percutaneous Coronary Intervention; Registries; Severity of Illness Index

The purposes of this study were to probe spectral behaviors of the toxic targets in trans-crotonaldehyde (TCA) in mitochondria altered by diallyl disulfides (DADS) derived from garlic. Ultraviolet absorption spectra showed that when ethanol as a solvent, the DADS blue shifted the peak of TCA from 318 nm to 312 nm. In mitochondria, the DADS further blue displaced the peak of TCA from 312 nm to 308 nm. Raman spectra displayed that the SS of DADS directly interacted with the CC toxic target of TCA, then the CCC of DADS interacted with the CHO toxic target of TCA. When DADS to TCA was 1:2, the DADS was the most powerful for the removal of the CC and CHO toxic targets of TCA. Study suggested that the SS of DADS altered the CC toxic target of TCA, while the CCC of DADS eliminated the CHO toxic target of TCA via local electron delocalization. The above two together clearly depicted the spectral behaviors of the toxic targets of TCA in mitochondria altered by DADS. These results are of great significance and value to elucidate the effects of garlic organic polysulfide on myocardial ischemia for the extensive development and use of garlic extracts.

Topics: Aldehydes; Allyl Compounds; Animals; Cardiovascular Agents; Cells, Cultured; Disulfides; Male; Mitochondria; Myocardial Ischemia; Myocardium; Rats; Rats, Wistar

Acute ischemic cardiogenic shock is associated with poor prognosis, and the impact of inotropic support on diastolic function in this context is unclear. We assessed two suggested new inotropic strategies in a clinically relevant pig model of ischemic acute heart failure (AHF): treatment with the myosin activator omecamtiv mecarbil (OM) or dobutamine and ivabradine (D+I). Left ventricular (LV) ischemia was induced in anesthetized pigs by coronary microembolization (n = 12). The animals then received OM (bolus 0.75 mg/kg, followed by 0.5 mg/kg per h) (n = 6) or D+I (5 μg/kg per min + 0.29 ± 0.16 mg/kg) (n = 6), respectively. Ischemia reduced the stroke volume (SV), despite the increased left atrial pressure associated with impaired LV early relaxation, systolic dilatation, and LV late diastolic stiffness. Both treatments improved systolic ejection, but only D+I increased the SV from 26 ± 5 to 33 ± 5 mL. D+I enhanced LV early relaxation (Tau; from 45 ± 11 to 29 ± 4 msec) and prolonged the diastolic time (DT) from 338 ± 60 to 352 ± 40 msec. In contrast, OM prolonged Tau (42 ± 5 to 62 ± 10 msec) and shortened the DT (from 326 ± 68 to 248 ± 84 msec). Our data suggest that enhanced early relaxation by D+I improves LV pump function in postischemic acute heart failure. In contrast, OM worsened lusitropy in this model.

Topics: Animals; Cardiotonic Agents; Cardiovascular Agents; Diastole; Dobutamine; Drug Therapy, Combination; Heart Failure; Ivabradine; Male; Myocardial Ischemia; Swine; Treatment Outcome; Urea

Coronary artery spasm (CAS) could cause serious lethal ventricular arrhythmias. While implantable cardioverter defibrillators (ICDs) have been recommend for secondary prevention of sudden cardiac death related to lethal ventricular arrhythmias. However, in resuscitated sudden cardiac death caused by CAS, the effect of ICD is still not well clear.. A 60-year-old male presented with 2 episodes of syncope. Coronary angiography showed normal coronary arteries. Twenty-four hour Holter electrocardiograms revealed that there were repeatedly transient marked ST segment elevation in the all leads except avR lead, junctional rhythm, and subsequently nonsustained ventricular tachycardia.. Ischemic-induced lethal ventricular arrhythmias caused by CAS.. Both calcium channel blocker (diltiazem, 180 mg twice daily) and nitrate (isosorbide dinitrate 40 mg twice daily) were initially administrated, and ICD was subsequently implanted as a secondary prevention.. In the early stage of CAS, ICD therapy terminated the lethal ventricular arrhythmias. Conversely, after the administration of epinephrine, ICD therapy, even combined with external defibrillation, failed in resuscitating sudden cardiac death.. For the sudden cardiac death related to lethal ventricular arrhythmias caused by CAS, ICD therapy is an efficient secondary prevention base on administrating coronary vasodilators. Furthermore, administration of epinephrine should be avoided during cardiorespiratory resuscitation of sudden cardiac death caused by CAS.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Coronary Vasospasm; Death, Sudden, Cardiac; Defibrillators, Implantable; Fatal Outcome; Humans; Male; Middle Aged; Myocardial Ischemia

Coronary artery disease is the most prevalent cardiovascular disease. In the United States, 7% of adults over 20 years of age are estimated to have coronary artery disease. In Brazil, a prevalence of 5 to 8% has been estimated in adults over 40 years of age, with an increased number of hospitalizations associated with both stable and acute clinical manifestations; and health care costs have quadrupled in the last decade. To estimate the direct costs of managing ischemic heart disease patient care in a teaching hospital in Brazil from the perspective of the service payer, the Brazilian Unified Health System.. This study was a retrospective cohort study for the identification and valuation of resources used at both the outpatient and in-hospital levels in a sample of 330 patients selected from the hospital's ischemic heart disease clinic. Data were collected from computerized hospital records and patients' hospital bills from January 2000 to October 2015. A bivariate analysis and binary logistic regression were performed with p < 0.05 considered statistically significant.. The study population consisted of 330 patients with a mean age 61 ± 10 years and a follow-up period of 107 ± 2.6 months; of the patients, 55% were male, 89% had hypertension, 48% had diabetes, and 65% had acute myocardial infarction. The mean annual cost of outpatient management was US $1,521 per patient. The mean cost per hospitalization was US $1,976, and the expenses were higher in the first and last years of follow-up. Unstable angina, revascularization procedures, diabetes, hypertension and obesity were predictors of higher hospitalization costs (p <0.05).. The cost estimates in this study indicate a high proportion of drug treatment costs in the treatment of ischemic heart disease. Treatment costs are higher in the first year and at the end of treatment, and some clinical factors are associated with greater hospital care costs. These results may serve as a basis for the evaluation of existing public policies and inputs for cost-effectiveness studies in coronary artery disease.. CEP HCPA 11-0460 . Ethics Committee of Hospital de Clínicas de Porto Alegre.

Topics: Aged; Ambulatory Care; Brazil; Cardiovascular Agents; Comorbidity; Drug Costs; Female; Hospital Costs; Hospitals, Teaching; Humans; Linear Models; Logistic Models; Male; Middle Aged; Models, Economic; Myocardial Ischemia; Process Assessment, Health Care; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome

The burden of heart failure has long plagued the productive years of the population, with therapeutic advances in the timely treatment of ischemic heart disease decreasing its associated mortality. Angiotensin-converting enzyme inhibitors and β-blockers have impacted heart failure therapeutics in a revolutionary way. The importance of blockade of the renin-angiotensin system and adrenergic stimulation are fully accepted concepts that apply in young and old, symptomatic and asymptomatic, borderline low and very low Ejection Fraction (EF), left ventricular failure and biventricular failure. Despite several interventions, both pharmaceutical and device based for the treatment of ensuing heart failure, the incidence is increasing in large proportions. Newer molecules like sacubitril show more promise. Despite these novel therapies, several patients relentlessly progress to a stage of advanced heart failure. The use of left-ventricular-assist devices has variable clinical benefit, with some patients progressing to heart transplantation.

Topics: Cardiac Surgical Procedures; Cardiomyopathies; Cardiovascular Agents; Disease Progression; Heart Failure; Heart-Assist Devices; Hemodynamics; Humans; Models, Cardiovascular; Myocardial Ischemia; Recovery of Function; Renin-Angiotensin System; Risk Factors; Stroke Volume; Treatment Outcome; Ventricular Function, Left

to assess efficacy and endotheliotropic properties of short-term addition of meldonium to basic therapy of patients with chronic ischemic heart failure and type 2 diabetes.. The study demonstrated the ability of meldonium to significantly improve endothelial function and the state of microcirculatory vascular bed, as well as to influence beneficially heart rate variability.

Topics: Aged; Cardiovascular Agents; Chronic Disease; Diabetes Mellitus, Type 2; Female; Heart Failure; Heart Rate; Humans; Male; Methylhydrazines; Middle Aged; Myocardial Ischemia

Increase in heart rate triggers most ischemic episodes due to disbalance between myocardial oxygen delivery and consumption. Furthermore, increased heart rate is a modifiable risk factor in patients with chronic heart failure. Ivabradine reduces heart rate by selectively inhibiting the If current of sinoatrial node cells. Recent studies have shown that ivabradine may reduce myocardial ischaemia and its consequences not only through heart rate reduction, but also because of additional pleiotropic effects. This review summarizes last findings that demonstrate variety of ivabradine actions on coronary blood flow and left ventricular function in patients with ischemic heart disease.

Topics: Angina, Stable; Benzazepines; Cardiovascular Agents; Heart Failure; Heart Rate; Hemodynamics; Humans; Ivabradine; Myocardial Ischemia; Sinoatrial Node

Patients with microvascular angina are characterized by angina pectoris with proof of myocardial ischemia in the absence of any relevant epicardial stenosis and without myocardial disease (type 1 coronary microvascular dysfunction according to Crea and Camici). Structural and functional alterations of the coronary microvessels (diameter < 500 µm) are the reason for this phenomenon. Frequently such alterations are associated with cardiovascular risk factors. Patients with angina pectoris without epicardial stenoses represent for 10 - 50 % of all patients undergoing coronary angiography depending on the clinical presentation. Diagnostic approaches include non-invasive (e. g. combination of coronary CT-angiography and positron emission tomography/echo Doppler-based coronary flow reserve measurements) as well as invasive procedures (coronary flow reserve measurements in response to adenosine, intracoronary acetylcholine testing). Pharmacological treatment of these patients is often challenging and should be based on the characterization of the underlying mechanisms. Moreover, strict risk factor control and individually titrated combinations of antianginal substances (e. g. beta blockers, calcium channel blockers, nitrates, ranolazine, ivabradine etc.) are recommended.

Topics: Adrenergic beta-Antagonists; Calcium Channel Blockers; Cardiovascular Agents; Coronary Vasospasm; Coronary Vessels; Humans; Implantable Neurostimulators; Microvascular Angina; Myocardial Ischemia; Physical Conditioning, Human; Risk Factors; Sodium Channel Blockers

Herbal medicine is a concoction of numerous chemical ingredients, and it exhibits polypharmacological effects to act on multiple pharmacological targets, regulating different biological mechanisms and treating a variety of diseases. Thus, this complexity is impossible to deconvolute by the reductionist method of extracting one active ingredient acting on one biological target.. To dissect the polypharmacological effects of herbal medicines and their underling pharmacological targets as well as their corresponding active ingredients.. We propose a system-biology strategy that combines omics and bioinformatical methodologies for exploring the polypharmacology of herbal mixtures. The myocardial ischemia model was induced by Ameroid constriction of the left anterior descending coronary in Ba-Ma miniature pigs. RNA-seq analysis was utilized to find the differential genes induced by myocardial ischemia in pigs treated with formula QSKL. A transcriptome-based inference method was used to find the landmark drugs with similar mechanisms to QSKL.. Gene-level analysis of RNA-seq data in QSKL-treated cases versus control animals yields 279 differential genes. Transcriptome-based inference methods identified 80 landmark drugs that covered nearly all drug classes. Then, based on the landmark drugs, 155 potential pharmacological targets and 57 indications were identified for QSKL.. Our results demonstrate the power of a combined approach for exploring the pharmacological target and chemical space of herbal medicines. We hope that our method could enhance our understanding of the molecular mechanisms of herbal systems and further accelerate the exploration of the value of traditional herbal medicine systems.

Topics: Animals; Cardiovascular Agents; Disease Models, Animal; Drug Discovery; Gene Expression Profiling; Gene Regulatory Networks; Herbal Medicine; Molecular Targeted Therapy; Myocardial Ischemia; Plant Preparations; Polypharmacology; Protein Interaction Maps; Swine; Swine, Miniature; Systems Biology; Transcriptome

Topics: Animals; Cardiovascular Agents; Diabetes Mellitus, Experimental; Disease Models, Animal; Glycation End Products, Advanced; Male; MAP Kinase Signaling System; Myocardial Ischemia; Rats, Wistar; Receptor for Advanced Glycation End Products; Reperfusion Injury; Signal Transduction; Treatment Outcome; Xanthones

Previous studies have indicated that the Ilex genus exhibits antioxidant, neuroprotective, hepatoprotective, and anti-inflammatory activities. However, the pharmacologic action and mechanisms of Ilex cornuta against cardiac diseases have not yet been explored. The present study was designed to investigate the antioxidant and cardioprotective effects of Ilex cornuta root with in vitro and in vivo models. The anti-oxidative effects of the extract of Ilex cornuta root (ICR) were measured by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging and MTT assays as well as immunoassay. Furthermore, a rat model of myocardial ischemia was established to investigate the cardioprotective effect of ICR in vivo. Eight compounds were isolated and identified from ICR and exhibited DPPH free-radical scavenging activities. They also could increase cell viability and inhibit morphological changes induced by H

Topics: Animals; Antioxidants; Apoptosis; Cardiovascular Agents; Cell Survival; Hydrogen Peroxide; Ilex; Malondialdehyde; Myocardial Infarction; Myocardial Ischemia; Myocardium; Myocytes, Cardiac; Oxidative Stress; Phytotherapy; Plant Extracts; Plant Roots; Rats, Sprague-Dawley; Reactive Oxygen Species; Superoxide Dismutase

Perhexiline, originally used as a first-line prophylactic antianginal agent, is now regarded primarily as a treatment for otherwise refractory myocardial ischemia. Recent studies have also demonstrated its short-term utility in heart failure, hypertrophic cardiomyopathy, and inoperable aortic stenosis. Its benefits on myocardial energetics state are potentially counter-balanced by risk of hepatotoxicity and peripheral neuropathy during long-term treatment if drug accumulation occurs. Since perhexiline exhibits complex pharmacokinetics with wide inter-individual variability, its long-term use requires regular plasma concentration monitoring. In this study, the risk of neuro- and hepato-toxicity during long-term perhexiline therapy in relation to the intensity of therapeutic drug monitoring was investigated. Furthermore, determinants of mortality during perhexiline treatment were evaluated.. In 170 patients treated with perhexiline for a median of 50 months (interquartile range: 31-94 months), outcomes and relationship to plasma drug concentrations were documented.. Rationale for treatment with perhexiline included myocardial ischemia in 88% and severe systolic heart failure in 38%. Plasma concentrations were within the therapeutic range of 150-600 ng/mL on 65% of assay occasions and toxic levels accounted for 8.8% of measurements. No patient developed hepatotoxicity attributable to perhexiline while 3 developed peripheral neuropathy possibly induced by treatment. Actuarial 5-year survival rate was 83% overall, and 76.3% in patients with associated systolic heart failure.. This first audit of a large population treated long-term perhexiline demonstrates the following: (1) Although the frequency of monitoring is less than ideal, therapeutic drug monitoring effectively limits occurrence of toxic drug concentrations and virtually eliminates long-term hepato- and neuro-toxicity and (2) Mortality rates during long-term therapy, notably for patients with concomitant heart failure, are surprisingly low.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Drug Monitoring; Female; Follow-Up Studies; Heart Failure, Systolic; Humans; Male; Myocardial Ischemia; Perhexiline; Survival Rate; Time Factors

Chronic ischaemic cardiovascular disease (CICD) is a major cause of mortality and morbidity worldwide. The primary objective of the CICD-Pilot registry was to describe the clinical characteristics and management modalities across Europe in a broad spectrum of patients with CICD.. The CICD-Pilot registry is an international prospective observational longitudinal registry, conducted in 100 centres from 10 countries selected to reflect the diversity of health systems and care attitudes across Europe. From April 2013 to December 2014, 2420 consecutive CICD patients with non-ST-elevation acute coronary syndrome (n = 755) and chronic stable coronary artery disease (n = 1464), of whom 933 (63.7%) were planned for elective coronary intervention, or with peripheral artery disease (PAD) (n = 201), were enrolled (30.5% female patients). Mean age was 66.6 ± 10.9 years. The following risk factors were reported: smoking 54.6%, diabetes mellitus 29.2%, hypertension 82.6%, and hypercholesterolaemia 74.1%. Assessment of cardiac function was made in 69.5% and an exercise stress test in 21.2% during/within 1 year preceding admission. New stress imaging modalities were applied in a minority of patients. A marked increase was observed at discharge in the rate of prescription of angiotensin-converting enzyme-inhibitors/angiotensin receptor blockers (82.8%), beta-blockers (80.2%), statins (92.7%), aspirin (90.3%), and clopidogrel (66.8%). Marked differences in clinical profile and treatment modalities were observed across the four cohorts.. The CICD-Pilot registry suggests that implementation of guideline-recommended therapies has improved since the previous surveys but that important heterogeneity exists in the clinical profile and treatment modalities in the different cohorts of patients enrolled with a broad spectrum of CICDs.

Topics: Aged; Biomarkers; Cardiovascular Agents; Chronic Disease; Europe; Female; Guideline Adherence; Hospitalization; Humans; Male; Myocardial Ischemia; Pilot Projects; Practice Guidelines as Topic; Prospective Studies; Registries

This study aimed to investigate whether sedentary work is a distinct risk factor for ischemic heart disease (IHD) when the effect of occupational sitting is disentangled from that of occupational physical activity.. Data on occupational sitting time and several covariates were derived from the Danish Work Environment Cohort Study (DWECS) conducted every five years from 1990-2005 among the active Danish population. This study was designed as a multi-wave longitudinal study including participants employed at entry. Respondents were followed in national registers, first for death or hospital treatment due to IHD and second for purchase of medication that may prevent IHD from (re)occurring serving as a proxy for IHD.. During 145 850 person-years of follow-up, 510 cases of fatal and non-fatal IHD occurred. After adjustment for age, sex, body mass index (BMI), and socioeconomic status, no difference in risk of IHD was observed between sedentary and non-sedentary employees [hazard ratio (HR) 0.95, 95% confidence interval (95% CI) 0.78-1.16]. During 44 949 and 42 456 person-years of follow-up among men and and women, respectively, 1263 men and 1364 women purchased IHD-related medication. No differences in risk were observed between sedentary and non-sedentary participants, either for men or women. A dose-response relationship between occupational sitting time and the risk of IHD was also not detected.. This study could not confirm the hypothesis that sedentary work is a distinct risk factor for IHD. Future studies may further investigate the association with objective measures of occupational sitting time.

Topics: Adult; Cardiovascular Agents; Denmark; Exercise; Female; Humans; Interviews as Topic; Leisure Activities; Longitudinal Studies; Male; Middle Aged; Myocardial Ischemia; Occupational Health; Prospective Studies; Risk Assessment; Risk Factors; Sedentary Behavior; Workplace

Over the past decade, landmark randomized clinical trials comparing initial management strategies in stable ischemic heart disease (SIHD) have demonstrated no significant reduction in 'hard' end points (all-cause mortality, cardiac death or myocardial infarction) with one strategy versus another. The main advantage derived from early revascularization is improved short-term quality of life. Nonetheless, questions remain regarding how best to manage SIHD patients, such as whether a high-risk subgroup can be identified that may experience a survival or myocardial infarction benefit from early revascularization, and if not, when should diagnostic catheterization and revascularization be performed. The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial is designed to address these questions by randomizing SIHD patients with at least moderate ischemia to an initial conservative strategy of optimal medical therapy or an initial invasive strategy of optimal medical therapy plus cardiac catheterization and revascularization.

Topics: Cardiac Catheterization; Cardiovascular Agents; Humans; Myocardial Ischemia; Myocardial Revascularization; Practice Guidelines as Topic; Randomized Controlled Trials as Topic

This survey study was performed to provide an overall picture on the incidence of symptoms, with or without typical angina, in the real-life clinical practice and to identify clinical factors associated with atypical presentations in an unselected population of consecutive outpatients with chronic coronary artery disease (CAD).. Thirty-six cardiology units located in different geographic areas of Italy enrolled a total of 1475 outpatients (73.6% men and 26.3% women; mean age 71 ± 10 and 67 ± 9 years in men and women, respectively) with a documented diagnosis of chronic CAD. Each patient underwent a medical history, with a detailed investigation as to the presence of typical angina or ischemic equivalents defined as sensation of chest pressure, or arm, neck, or jaw pain.. At admission, symptoms suggesting ischemic episodes were reported by 24.4% of patients. After an in-depth medical history collection by the specialist, the prevalence of combined typical or atypical myocardial ischemic episodes was ascertained in 39.3% of the overall population.Typical angina was reported by 13.6% of men and 22.7% of women (P < 0.0001), whereas ischemic equivalents were present in 7.3 and 12.9% of male and female patients, respectively (P < 0.001). Previous coronary artery bypass grafting (CABG; P < 0.001) and fewer medical visits by cardiologists (P = 0.02) were independent predictors of atypical presentations.. The ISPICA study shows that in an Italian population of real-world patients with chronic CAD, ischemic episodes, with both typical and atypical presentation, are still present in nearly 50% of patients, despite optimal medical therapy, and that atypical presentations of angina are linked to fewer visits by specialists and previous CABG. These findings would suggest to encourage patients with chronic CAD and general practitioners to consider more frequent cardiology specialist visits and to take into account the possibility of atypical presentations, particularly in patients with previous CABG.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Cardiovascular Agents; Chronic Disease; Coronary Artery Disease; Female; Health Surveys; Humans; Incidence; Italy; Male; Middle Aged; Myocardial Ischemia; Myocardial Revascularization; Risk Factors

Successful reperfusion is the most effective strategy to reduce ischemic injury in acute myocardial infarction (AMI). Ischemic injury, however, also triggers a secondary ischemia-independent injury, known as reperfusion injury, contributing to the overall infarct size. We hypothesize that inhibition of the Nod-like Receptor Protein-3 (NLRP3) inflammasome limits infarct size following myocardial ischemia/reperfusion (I/R), by inhibiting the inflammatory component of the reperfusion injury.. CD-1 male mice underwent transient ligation of the left anterior descending coronary artery for 30 or 75min followed by reperfusion. Infarct size was measured at 1, 3 and 24h. A NLRP3 inflammasome inhibitor (NLRP3inh) or vehicle was administrated immediately at time of reperfusion or with a delay of 1 or 3h of reperfusion.. A time-dependent increase in infarct size was measured at 1, 3, and 24h after reperfusion (11±2%, 30±5% and 43±4% of the area at risk respectively; P<0.001 for trend). NLRP3 myocardial expression was significantly increased at 24h and 6h vs 3h (P<0.01). Administration of the NLRP3inh at reperfusion did not reduce infarct size at 3h, while it significantly reduced infarct size at 24h (-56% vs vehicle, P<0.01). The NLRP3inh given 1h after reperfusion also significantly decreased caspase-1 activity and infarct size measured at 24h, whereas the NLRP3inh did not when given with a delay of 3h.. Pharmacological inhibition of the NLRP3 inflammasome within 1h of reperfusion limits the secondary inflammatory injury and infarct size following myocardial ischemia-reperfusion in the mouse.

Topics: Animals; Cardiovascular Agents; Inflammasomes; Male; Mice; Mice, Inbred ICR; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Reperfusion Injury; NLR Family, Pyrin Domain-Containing 3 Protein

It is the aim of this manuscript to take into account the peculiarities and specific characteristics of elderly patients with chronic ischaemic heart disease from a multidisciplinary perspective, with the participation of the Spanish Society of Cardiology (sections of Geriatric Cardiology and Ischaemic Heart Disease/Acute Cardiovascular Care), the Spanish Society of Internal Medicine, the Spanish Society of Primary Care Physicians and the Spanish Society of Geriatrics and Gerontology. This consensus document shows that in order to adequately address these elderly patients a comprehensive assessment is needed, which includes comorbidity, frailty, functional status, polypharmacy and drug interactions. We conclude that in most patients medical treatment is the best option and that this treatment must take into account the above factors and the biological changes associated with aging.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Chronic Disease; Combined Modality Therapy; Comorbidity; Drug Interactions; Frail Elderly; Geriatric Assessment; Humans; Myocardial Ischemia; Percutaneous Coronary Intervention; Polypharmacy; Spain

Refractory angina pectoris (RAP) represents a clinical condition characterized by frequent episodes of chest pain despite therapy optimization. According to myocardial stunning and myocardial hibernation definitions, RAP should represent the ideal condition for systolic dysfunction development. We aim to investigate the evolution of left ventricular (LV) function in patients with RAP. A retrospective study which encompasses 144 patients with RAP referred to our institution from 1999 to December 2014 was performed. Of them, 88 met the inclusion criteria, and LV function was assessed by echocardiography. All of them had persistent angina episodes on top of optimal medical therapy and evidence of significant inducible myocardial ischemia and no further revascularization options. Nitrates consumption rate, time of angina duration, and the number of angina attacks were evaluated. In the whole population, ejection fraction (EF) was 44% ± 2. EF was significantly lower in patients with previous myocardial infarction (41% ± 1.5 vs 51% ± 1.8, p <0.0001). The duration time and the number of angina attacks did not correlate with EF in the whole population and in patients without previous myocardial infarction. In patients with previous myocardial infarction, the number of anginal attacks did not correlate with EF, but EF appeared higher in patients with angina duration >5 years (<5 years EF 37% ± 1 [n = 26]; >5 years 44% ± 2 [n = 44]; p 0.02). Long-term LV function in patients with RAP is generally preserved. A previous history of myocardial infarction is the only determinant in the development of systolic dysfunction. In conclusion, frequent angina attacks and a long-term history of angina are not apparently associated to worse LV function.

Topics: Aged; Angina Pectoris; Benzazepines; Cardiovascular Agents; Echocardiography; Exercise Test; Female; Follow-Up Studies; Humans; Ivabradine; Male; Myocardial Ischemia; Ranolazine; Retrospective Studies; Sodium Channel Blockers; Stroke Volume; Systole; Time Factors; Tomography, Emission-Computed, Single-Photon; Trimetazidine; Vasodilator Agents; Ventricular Function, Left

Therapeutic strategies aimed at increasing hydrogen sulfide (H2S) levels exert cytoprotective effects in various models of cardiovascular injury. However, the underlying mechanism(s) responsible for this protection remain to be fully elucidated. Nuclear factor E2-related factor 2 (Nrf2) is a cellular target of H2S and facilitator of H2S-mediated cardioprotection after acute myocardial infarction. Here, we tested the hypothesis that Nrf2 mediates the cardioprotective effects of H2S therapy in the setting of heart failure.. Mice (12 weeks of age) deficient in Nrf2 (Nrf2 KO; C57BL/6J background) and wild-type littermates were subjected to ischemic-induced heart failure. Wild-type mice treated with H2S in the form of sodium sulfide (Na2S) displayed enhanced Nrf2 signaling, improved left ventricular function, and less cardiac hypertrophy after the induction of heart failure. In contrast, Na2S therapy failed to provide protection against heart failure in Nrf2 KO mice. Studies aimed at evaluating the underlying cardioprotective mechanisms found that Na2S increased the expression of proteasome subunits, resulting in an increased proteasome activity and a reduction in the accumulation of damaged proteins. In contrast, Na2S therapy failed to enhance the proteasome and failed to attenuate the accumulation of damaged proteins in Nrf2 KO mice. Additionally, Na2S failed to improve cardiac function when the proteasome was inhibited.. These findings indicate that Na2S therapy enhances proteasomal activity and function during the development of heart failure in an Nrf2-dependent manner and that this enhancement leads to attenuation in cardiac dysfunction.

Topics: Animals; Cardiovascular Agents; Disease Models, Animal; Endoplasmic Reticulum Stress; Heart Failure; Hydrogen Sulfide; Hypertrophy, Left Ventricular; Male; Mice, Inbred C57BL; Mice, Knockout; Myocardial Ischemia; Myocardium; NF-E2-Related Factor 2; Oxidative Stress; Proteasome Endopeptidase Complex; Signal Transduction; Sulfides; Time Factors; Ventricular Function, Left

Myocardial ischemia (MI) is one of the leading causes of death, while Qishen Yiqi Drop Pill (QYDP) is a representative traditional Chinese medicine to treat this disease. Unveiling the pharmacological mechanism of QYDP will provide a great opportunity to promote the development of novel drugs to treat MI. 64 male Sprague-Dawley (SD) rats were divided into four groups: MI model group, sham operation group, QYDP treatment group and Fosinopril treatment group. Echocardiography results showed that QYDP exhibited significantly larger LV end-diastolic dimension (LVEDd) and LV end-systolic dimension (LVEDs), compared with the MI model group, indicating the improved cardiac function by QYDP. (1)H-NMR based metabonomics further identify 9 significantly changed metabolites in the QYDP treatment group, and the QYDP-related proteins based on the protein-metabolite interaction networks and the corresponding pathways were explored, involving the pyruvate metabolism pathway, the retinol metabolism pathway, the tyrosine metabolism pathway and the purine metabolism pathway, suggesting that QYDP was closely associated with blood circulation. ELISA tests were further employed to identify NO synthase (iNOS) and cathepsin K (CTSK) in the networks. For the first time, our work combined experimental and computational methods to study the mechanism of the formula of traditional Chinese medicine.

Topics: Animals; Cardiovascular Agents; Disease Models, Animal; Drugs, Chinese Herbal; Echocardiography; Enzyme-Linked Immunosorbent Assay; Magnetic Resonance Spectroscopy; Metabolomics; Myocardial Ischemia; Myocardium; Rats, Sprague-Dawley; Treatment Outcome

Topics: Aged; Cardiomyopathies; Cardiovascular Agents; Female; Heart Failure, Systolic; Humans; Male; Middle Aged; Mortality; Myocardial Ischemia; Retrospective Studies

Almost a third of outpatients with chronic coronary artery disease (CAD) report having angina in the prior month, which is frequently under-recognized by their cardiologists. Whether under-recognition is associated with less treatment escalation to control angina, and potential underuse of treatment, is unknown.. Patients with CAD from 25 US cardiology outpatient practices completed the Seattle Angina Questionnaire (SAQ) prior to their clinic visit, and angina was categorized as daily, weekly, monthly and no angina. Cardiologists (n=155) independently quantified patients' angina, blinded to patients' SAQ scores. Under-recognition was defined as the physician reporting a lower category of angina frequency than the patient. Among 1257 patients with CAD, 411 reported angina in the past month, of whom 178 (43.3%) patients were under-recognized. Treatment escalation-defined as intensification (up-titration or addition) of antianginal medications, referral for diagnostic testing or revascularization, or hospital admission-occurred in 106 (25.8%) patients with angina. Patients with under-recognized angina were less likely to get treatment escalation than patients whose angina was appropriately recognized (8.4% vs 39.1%, P<0.001). In a hierarchical multivariable logistic regression model adjusting for demographic and clinical characteristics, as well as the burden of angina, under-recognition remained strongly associated with a lack of treatment escalation (adjusted OR 0.10, 95% CI 0.04-0.21, P<0.001).. Under-recognition of angina in cardiology outpatient practices is associated with less aggressive treatment escalation and may lead to poorer angina control. Standardizing clinical recognition of angina using validated tools could reduce under-recognition of angina, facilitate treatment, and potentially improve outcomes.

Topics: Aged; Aged, 80 and over; Angina Pectoris; Cardiologists; Cardiovascular Agents; Clinical Competence; Coronary Artery Disease; Cross-Sectional Studies; Female; Health Status; Humans; Male; Middle Aged; Myocardial Ischemia; Outpatients; Practice Patterns, Physicians'; Prevalence; Quality Indicators, Health Care; United States

Topics: Aged; Cardiovascular Agents; Europe; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Russia; Treatment Outcome

to analyze clinical and economical effectiveness of meldonium as component of integrated program of cardio-rehabilitation in patients with ischemic heart disease (IHD) in the early period after percutaneous coronary intervention (PCI) with incomplete revascularization.. A program of controlled physical training (CPT) was carried out in patients with stable IHD and positive post PCI exercise test (n=48, age less or equal 65 years) starting 8-10 days after PCI. CRT program consisted of 2 phases - inhospital (exercise on treadmill with max heart rate [HR] 80% of that achieved in initial test, 10 times during 2 weeks) and home (exercise on treadmill with max HR 60% of HR achieved in initial test, 3 times a week for 2 months). Before initiation of CRT patients were distributed into 2 groups: CRT without (n=23; 56.7+/-7.1 years) and with (n=25; 54.6+/-6.8 years) administration of meldonium (1000 mg/day intravenously). Control group (n=24; 50+/-8.4 years) consisted of patients who were under outpatient observation, received similar drug therapy, but were not subjected to CRT. After completion of CRT (in 2.5 months) all patients underwent clinical-instrumental examination with determination of exercise tolerance.. Exercise duration and metabolic equivalent (MET) increased by 43.9, 36.6, 4.1% and 42.1, 34.8, 3.4% in CRT+ meldonium, CRT only, and control groups, respectively.. In patients with documented ischemia after PCI inclusion of meldonium in the scheme of rehabilitation was associated with improved physical performance and optimal cost-effectiviness.

Topics: Cardiovascular Agents; Coronary Disease; Exercise Test; Exercise Tolerance; Female; Humans; Male; Methylhydrazines; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Treatment Outcome

We report a 23-month old girl who presented with bilateral epiphora who underwent bilateral lacrimal probing and syringing, during which a cocaine adrenaline solution was used. Two hours after the procedure she developed acute pulmonary oedema secondary to myocardial ischaemia. The patient was treated with intravenous glyceryltrinitrate and milrinone infusions; cardiac enzymes and left ventricular function normalised over the subsequent 72 hours. Topical administration of cocaine and adrenaline solution may have dangerous systemic cardiac effects and should always be used judiciously.

Topics: Administration, Topical; Anesthetics, Local; Cardiovascular Agents; Cocaine; Diagnostic Techniques, Ophthalmological; Epinephrine; Female; Humans; Infant; Lacrimal Apparatus Diseases; Milrinone; Mydriatics; Myocardial Ischemia; Nitroglycerin; Treatment Outcome

Topics: American Heart Association; Cardiomyopathies; Cardiovascular Agents; Humans; Myocardial Ischemia; Randomized Controlled Trials as Topic; Stents; United States

The ratio of revascularization to medical therapy (referred to herein as the revascularization ratio) for the initial treatment of stable ischemic heart disease varies considerably across hospitals. We conducted a comprehensive study to identify patient, physician and hospital factors associated with variations in the revascularization ratio across 18 cardiac centres in the province of Ontario. We also explored whether clinical outcomes differed between hospitals with high, medium and low ratios.. We identified all patients in Ontario who had stable ischemic heart disease documented by index angiography performed between Oct. 1, 2008, and Sept. 30, 2011, at any of the 18 cardiac centres in the province. We classified patients by initial treatment strategy (medical therapy or revascularization). Hospitals were classified into equal tertiles based on their revascularization ratio. The primary outcome was all-cause mortality. Patient follow-up was until Dec. 31, 2012. Hierarchical logistic regression models identified predictors of revascularization. Multivariable Cox proportional hazards models, with a time-varying covariate for actual treatment received, were used to evaluate the impact of the revascularization ratio on clinical outcomes.. Variation in revascularization ratios was twofold across the hospitals. Patient factors accounted for 67.4% of the variation in revascularization ratios. Physician and hospital factors were not significantly associated with the variation. Significant patient-level predictors of revascularization were history of smoking, multivessel disease, high-risk findings on noninvasive stress testing and more severe symptoms of angina (v. no symptoms). Treatment at hospitals with a high revascularization ratio was associated with increased mortality compared with treatment at hospitals with a low ratio (hazard ratio 1.12, 95% confidence interval 1.03-1.21).. Most of the variation in revascularization ratios across hospitals was warranted, in that it was driven by patient factors. Nonetheless, the variation was associated with potentially important differences in mortality.

Topics: Age Factors; Aged; Angina, Stable; Cardiovascular Agents; Cohort Studies; Comorbidity; Coronary Angiography; Coronary Artery Bypass; Databases, Factual; Diabetes Mellitus; Exercise Test; Female; Hospitals; Humans; Hyperlipidemias; Hypertension; Income; Logistic Models; Male; Middle Aged; Myocardial Ischemia; Myocardial Revascularization; Ontario; Percutaneous Coronary Intervention; Peripheral Vascular Diseases; Practice Patterns, Physicians'; Proportional Hazards Models; Pulmonary Disease, Chronic Obstructive; Severity of Illness Index; Smoking

The management of stable coronary artery disease has evolved in recent years and is now based on the latest recommendations of the European Society of Cardiology. Drug prescription takes into account two strategic approaches: on the one hand, pharmacological treatments that improve the prognosis and on the other hand treatments to improve symptoms and/or ischemia. Improving the prognosis involves reducing as well as stabilizing coronary plaque thanks to 3 therapeutic classes: aspirin, statins and renin-angiotensin system blockers (ACE inhibitors or ARBs). In parallel, a fast-acting nitrovasodilator associated with a beta-blocker or a heart-slowing calcium-channel blocker makes it possible to reduce the angina. In addition, pharmacological modifications and regular reassessments are fundamental aspects of CAD management.

Topics: Cardiovascular Agents; Coronary Artery Disease; Diet; Drug Prescriptions; Humans; Hygiene; Myocardial Ischemia; Prognosis

Topics: Aged; Benzazepines; Cardiovascular Agents; Cyclic Nucleotide-Gated Cation Channels; Female; Follow-Up Studies; Humans; Ivabradine; Male; Myocardial Ischemia; Program Evaluation; Quality of Life; Retrospective Studies; Surveys and Questionnaires; Time Factors; Treatment Outcome

Mental stress can trigger myocardial ischemia, but the prevalence of mental stress-induced ischemia in congestive heart failure (CHF) patients is unknown. We characterized mental stress-induced and adenosine-induced changes in myocardial perfusion and neurohormonal activation in CHF patients with reduced left-ventricular function using SPECT to precisely quantify segment-level myocardial perfusion.. Thirty-four coronary artery disease patients (mean age±SD, 62±10 y) with CHF longer than 3 mo and ejection fraction less than 40% underwent both adenosine and mental stress myocardial perfusion SPECT on consecutive days. Mental stress consisted of anger recall (anger-provoking speech) followed by subtraction of serial sevens. The presence and extent of myocardial ischemia was quantified using the conventional 17-segment model.. Sixty-eight percent of patients had 1 ischemic segment or more during mental stress and 81% during adenosine. On segment-by-segment analysis, perfusion with mental stress and adenosine were highly correlated. No significant differences were found between any 2 time points for B-type natriuretic peptide, tumor necrosis factor-α, IL-1b, troponin, vascular endothelin growth factor, IL-17a, matrix metallopeptidase-9, or C-reactive protein. However, endothelin-1 and IL-6 increased, and IL-10 decreased, between the stressor and 30 min after stress. Left-ventricular end diastolic dimension was 179±65 mL at rest and increased to 217±71 after mental stress and 229±86 after adenosine (P<0.01 for both). Resting end systolic volume was 129±60 mL at rest and increased to 158±66 after mental stress (P<0.05) and 171±87 after adenosine (P<0.07), with no significant differences between adenosine and mental stress. Ejection fraction was 30±12 at baseline, 29±11 with mental stress, and 28±10 with adenosine (P=not significant).. There was high concordance between ischemic perfusion defects induced by adenosine and mental stress, suggesting that mental stress is equivalent to pharmacologic stress in eliciting clinically significant myocardial perfusion defects in CHF patients. Cardiac dilatation suggests clinically important changes with both conditions. Psychosocial stressors during daily life may contribute to the ischemic burden of CHF patients with coronary artery disease.

Topics: Adenosine; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Agents; Coronary Circulation; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Stress, Psychological; Tomography, Emission-Computed, Single-Photon; Ventricular Function, Left

Prospective data on the safety and efficacy of the wearable cardioverter defibrillator (WCD) in a real-world setting are lacking. The Prospective Registry of Patients Using the Wearable Defibrillator (WEARIT-II) Registry was designed to provide real-world data on the WCD as a strategy during a period of risk stratification.. The WEARIT-II Registry enrolled 2000 patients with ischemic (n=805, 40%), or nonischemic cardiomyopathy (n=927, 46%), or congenital/inherited heart disease (n=268) prescribed WCD between August 2011 and February 2014. Clinical data, arrhythmia events, implantable cardioverter defibrillator implantation, and improvement in ejection fraction were captured. The median age was 62 years; the median ejection fraction was 25%. The median WCD wear time was 90 days, with median daily use of 22.5 hours. There was a total of 120 sustained ventricular tachyarrhythmias in 41 patients, of whom 54% received appropriate WCD shock. Only 10 patients (0.5%) received inappropriate WCD therapy. The rate of sustained ventricular tachyarrhythmias by 3 months was 3% among patients with ischemic cardiomyopathy and congenital/inherited heart disease, and 1% among nonischemic patients (P=0.02). At the end of WCD use, 840 patients (42%) were implanted with an implantable cardioverter defibrillator. The most frequent reason not to implant an implantable cardioverter defibrillator following WCD use was improvement in ejection fraction.. The WEARIT-II Registry demonstrates a high rate of sustained ventricular tachyarrhythmias at 3 months in at-risk patients who are not eligible for an implantable cardioverter defibrillator, and suggests that the WCD can be safely used to protect patients during this period of risk assessment.

Topics: Aged; Arrhythmias, Cardiac; Cardiomyopathies; Cardiovascular Agents; Combined Modality Therapy; Death, Sudden, Cardiac; Defibrillators; Defibrillators, Implantable; Electric Countershock; Female; Follow-Up Studies; Heart Defects, Congenital; Humans; Male; Middle Aged; Myocardial Ischemia; Patient Compliance; Prescriptions; Prospective Studies; Registries; Stroke Volume

We assessed quality of life in 80 patients with ischemic heart disease and pronounced dysfunction of left ventricular myocardium. Forty patients underwent coronary bypass surgery and 40 patients received only medical therapy. Duration of follow-up was 7 years. Baseline quality of life was low in both groups. Degree of its lowering was positively related to functional class of angina and heart failure and negatively - to exercise tolerance. Incessant drug treatment was associated with moderate improvement of quality of life both in groups of patients subjected and not subjected to surgery.

Topics: Aged; Cardiovascular Agents; Coronary Artery Bypass; Exercise Tolerance; Female; Follow-Up Studies; Heart Failure; Humans; Male; Myocardial Ischemia; Quality of Life; Severity of Illness Index; Siberia; Ventricular Dysfunction, Left

Results of the multicenter open observational program NACHALO (evaluation of therapy in patients with combined coronary artery disease and heart failure as part of daily clinical practice), in which 569 doctors in 58 regions of the Russian Federation participated, were presented. The program included 2751 patients with ischemic heart disease, stable angina complicated by heart failure at the age from 25 to 94 years (mean age 62.6 ± 9.3 years). The follow-up period was 3 months, during which two visits were carried out--after 4 weeks and a final visit--12 weeks after the initiation of therapy. Despite treatment, angina attacks (mean 6.7 6.1 per week), increased blood pressure (average 145.1 ± 20.9/87.2 ± 1.8 mm Hg) and heart rate (average 85.8 ± 9.5 beats/min) were noted in patients before the inclusion in the program. The addition of ivabradine therapy resulted in a significant (p < 0.00001) reduction in heart rate to 73.2 ± 8.7 (at visit 1) and down to 65.2 ± 6.1 beats/min (at visit 2), the number of angina attacks per week to 3.8 (at visit 1) and 1.9 (at visit 2). There were significant (p < 0.00001) positive dynamics of the clinical wellness and the severity of symptoms in patients. Adverse effects that, according to doctors, were associated with the agent, were observed in only 0.15% of cases. Thus, in real clinical practice inhibitor of the if channels ivabradine has been shown to be highly effective in treatment of stable angina in patients with coronary artery disease complicated by heart failure.

Topics: Adult; Aged; Aged, 80 and over; Angina, Stable; Benzazepines; Cardiovascular Agents; Cyclic Nucleotide-Gated Cation Channels; Female; Follow-Up Studies; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Myocardial Ischemia; Treatment Outcome

This study investigated the effects of an adenosine receptor agonist, 2-octynyladenosine (YT-146), on mitochondrial function in ischemic and ischemic/reperfused hearts. Isolated rat hearts were perfused in the Langendorff manner with a constant flow rate, and exposed to 30 min of ischemia followed by 60 min of reperfusion. Preischemic treatment with YT-146 significantly improved postischemic recovery of left ventricular developed pressure. The high-energy phosphate content in reperfused hearts treated with YT-146 was also more greatly restored than in untreated hearts. YT-146 treatment attenuated the Na(+) content of a mitochondria-enriched fraction, but not the myocardial Na(+) content, at the end of ischemia. These results suggest that preischemic YT-146 treatment preserves the energy-producing ability of mitochondria during ischemia in the Na(+)-accumulated myocardium. YT-146 also attenuated both the sodium lactate-induced decrease in mitochondrial energy-producing ability and the increase in mitochondrial Na(+) concentration in the myocardial skinned fibers. YT-146 may attenuate Na(+) influx to myocardial mitochondria in ischemic cardiac cells, resulting in both preservation of the ability of mitochondria to produce energy and enhancement of the contractile recovery in reperfused hearts. Our findings suggest that the cardioprotective effects of YT-146 against ischemia/reperfusion injury are at least partially due to the preservation of mitochondrial function in the ischemic myocardium.

Topics: Adenosine; Adenosine Triphosphate; Alkynes; Animals; Cardiovascular Agents; Energy Metabolism; Heart; Male; Mitochondria, Heart; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Purinergic P1 Receptor Agonists; Rats, Wistar; Sodium

Although an increased heart rate (HR) is a strong predictor of poor prognosis in cases of chronic heart failure (HF), the clinical value of HR as a predictor in acute decompensated HF (ADHF) is unclear. Seventy-eight patients with nonischemic dilated cardiomyopathy (NIDCM) with sinus rhythm who were first hospitalized for ADHF from 2002 to 2010 were retrospectively investigated after exclusion of patients with tachycardia-induced cardiomyopathy. The patients were divided into two groups stratified by HR on admission with a median value of 113 beats/min (Group H with HR ≥ 113 beats/min; Group L with HR < 113 beats/min). Despite similar backgrounds, including pharmacotherapy for HF, HR changes responding to titration of β-blocker (BB) therapy and myocardial interstitial fibrosis, left ventricular (LV) ejection fractions improved more significantly 1 year later in Group H than in Group L (57 % ± 11 % vs. 46 % ± 12 %, P < 0.001). Cardiac event-free survival rates were also significantly improved in Group H (P = 0.038). Multiple regression analysis revealed that only the peak HR on admission was an independent predictor of LV reverse remodeling (LVRR) 1 year later (β = 0.396, P = 0.005). High HR on first admission for ADHF is a strong predictor of LVRR, with a better prognosis in the event of NIDCM in response to optimal pharmacotherapy, independent of pre-existing myocardial damage and subsequent HR reduction by BB therapy.

Topics: Adult; Aged; Cardiomyopathy, Dilated; Cardiovascular Agents; Disease-Free Survival; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Myocardial Ischemia; Patient Admission; Retrospective Studies; Risk Factors; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling

We evaluated the clinical value of a single measurement of high-sensitivity C-reactive protein (hs- CRP) in patients presenting to the emergency department with chest pain. We screened 408 consecutive patients of whom 292 comprised the final cohort for this study. Hs-CRP measured in the emergency department (ED) in patients presenting with chest pain and admitted for evaluation of acute myocardial infarction was neither sensitive nor specific in predicting acute myocardial infarction, myocardial ischemia on SPECT imaging, need for coronary revascularization, or cardiovascular or all-cause rehospitalization at 30 days. In addition, use of a specific CRP cut off >1 was not associated with an increase in all-cause rehospitalization at 30 days.

Topics: Acute Disease; Aged; C-Reactive Protein; Cardiovascular Agents; Chest Pain; Comorbidity; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Patient Readmission; Percutaneous Coronary Intervention; Sensitivity and Specificity; Severity of Illness Index

The aim of the present work was to establish whether or not prescribed medication is a usable risk indicator for work-related ischaemic heart disease (IHD), in Denmark.. Weighted Spearman rank correlation coefficients (rho) were used to evaluate the agreement between Standardised Hazard Ratios (SHR) for hospital treatment or death due to IHD and SHR for purchase of prescriptions for medicine that may prevent IHD from (re)occurring, among socio-occupational and economic activities groups in Denmark. The SHR were based on a 10-year prospective follow-up of 2 million people in Danish national registers 1996-2005.. We found approximately 7 times more cases of medicine usage (N = 411 651) than we did for hospital treatment or death (N = 55 684). The correlations between the 2 types of SHR were strong (rho = 0.94 for the socio-occupational groups; rho = 0.74 for the economic activities groups). We observed, however, one markedly contradictive result; the industrial group entitled 'general practitioner, dentists etc.' was associated both with significantly high rates of medicine usage (SHR = 1.15, 95% CI: 1.12-1.19) and significantly low rates of hospital treatment or death due to IHD (SHR = 0.80, 95% CI: 0.71-0.91).. Apart from a few caveats, the strong correlations obtained in the present study signify that purchase of a prescription for IHD-related medication is a usable risk indicator for IHD in the working population of Denmark. The usage of medicine data in addition to or instead of the use of death or hospital data in epidemiological studies on work-related IHD risk will bring about a tremendous increase in statistical power.

Topics: Adult; Cardiovascular Agents; Cause of Death; Denmark; Female; Follow-Up Studies; Hospitals; Humans; Incidence; Male; Middle Aged; Myocardial Ischemia; Prospective Studies; Registries; Risk Assessment; Risk Factors; Socioeconomic Factors; Young Adult

Topics: Benzazepines; Bisoprolol; Cardiovascular Agents; Comparative Effectiveness Research; Drug Monitoring; Drug Therapy, Combination; Exercise Tolerance; Female; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Myocardial Ischemia; Myocardial Revascularization; Postoperative Complications; Tachycardia; Treatment Outcome

Matrix metalloproteinases (MMPs) as well as their inhibitors (TIMPs) play a crucial role in controlling extracellular matrix turnover and have recently been associated with atherosclerosis, myocardial and vascular injury. Moreover, the genetic variability of MMP genes has been suggested to play an important role in vascular remodeling and age-related arterial stiffening. This study aims to describe associations of 14 selected polymorphisms in genes for MMPs and TIMPs with selected cardiovascular parameters (including central pulse pressure), clinical conditions and drug treatment profiles in 411 stable ischemic patients with preserved systolic function of the left ventricle. The genotyping of 14 single-nucleotide polymorphisms in 8 genes was carried out either using 5´ exonuclease (TaqMan®) reagents or by restriction analysis. Numerous associations of the investigated polymorphisms with systolic and diastolic blood pressure, maximum left ventricular end diastolic pressure and ejection fraction were observed. While some of the observed effects were found to be age-dependent, associations with clinical conditions (hypertension, diabetes mellitus, angina pectoris) were only observed in women and associations with four groups of drugs (statins, nitrates, calcium channel blockers, anti-aggregation drugs) were only observed in men. The results of this study indicate that the genetic variability of MMPs and TIMPs is an important factor which influences cardiovascular functions and may have important consequences for individual therapy customization in the future.

Topics: Blood Pressure; Cardiovascular Agents; Female; Genetic Variation; Humans; Male; Matrix Metalloproteinases; Myocardial Ischemia; Tissue Inhibitor of Metalloproteinases

Topics: Cardiovascular Agents; Chest Pain; Dyspnea; Humans; Myocardial Ischemia; Myocardial Revascularization; Prognosis; Quality of Life; Surveys and Questionnaires; Symptom Assessment

This study sought to compare the survival of asymptomatic patients with previous revascularization and ischemia, who subsequently underwent repeat revascularization or medical therapy (MT).. Coronary artery disease is progressive and recurring; thus, stress myocardial perfusion scintigraphy (MPS) is widely used to identify ischemia in patients with previous revascularization.. Of 6,750 patients with previous revascularization undergoing MPS between January 1, 2005, and December 31, 2007, we identified 769 patients (age 67.7 ± 9.5 years; 85% men) who had ischemia and were asymptomatic. A propensity score was developed to express the associations of revascularization. Patients were followed up over a median of 5.7 years (interquartile range: 4.7 to 6.4 years) for all-cause death. A Cox proportional hazards model was used to identify the association of revascularization with all-cause death, with and without adjustment for the propensity score. The model was repeated in propensity-matched groups undergoing MT versus revascularization.. Among 769 patients, 115 (15%) underwent revascularization a median of 13 days (interquartile range: 6 to 31 days) after MPS. There were 142 deaths; mortality with MT and revascularization were 18.3% and 19.1% (p = 0.84). In a Cox proportional hazards model (chi-square test = 89.4) adjusting for baseline characteristics, type of previous revascularization, MPS data, and propensity scores, only age and hypercholesterolemia but not revascularization were associated with mortality. This result was confirmed in a propensity-matched group.. Asymptomatic patients with previous revascularization and inducible ischemia on MPS realize no survival benefit from repeat revascularization. In this group of post-revascularization patients, an ischemia-based treatment strategy did not alter mortality.

Topics: Age Factors; Aged; Asymptomatic Diseases; Cardiovascular Agents; Cause of Death; Coronary Artery Disease; Disease Progression; Female; Humans; Hypercholesterolemia; Male; Middle Aged; Myocardial Ischemia; Myocardial Perfusion Imaging; Myocardial Revascularization; Outcome Assessment, Health Care; Postoperative Complications; Proportional Hazards Models; Reoperation; Risk Assessment

Although the recent surgical treatment of ischemic heart failure substudy reported that revascularization of viable myocardium did not improve survival, these results were limited by the viability imaging technique used and the lack of inducible ischemia information. We examined the relative impact of stress-rest rubidium-82/F-18 fluorodeoxyglucose positron emission tomography identified ischemia, scar, and hibernating myocardium on the survival benefit associated with revascularization in patients with systolic dysfunction.. The extent of perfusion defects and metabolism-perfusion mismatch was measured with an automated quantitative method in 648 consecutive patients (age, 65±12 years; 23% women; mean left ventricular ejection fraction, 31±12%) undergoing positron emission tomography. Follow-up time began at 92 days (to avoid waiting-time bias); deaths before 92 days were excluded from the analysis. During a mean follow-up of 2.8±1.2 years, 165 deaths (27.5%) occurred. Cox proportional hazards modeling was used to adjust for potential confounders, including a propensity score to adjust for nonrandomized treatment allocation. Early revascularization was performed within 92 days of positron emission tomography in 199 patients (33%). Hibernating myocardium, ischemic myocardium, and scarred myocardium were associated with all-cause death (P=0.0015, 0.0038, and 0.0010, respectively). An interaction between treatment and hibernating myocardium was present such that early revascularization in the setting of significant hibernating myocardium was associated with improved survival compared with medical therapy, especially when the extent of viability exceeded 10% of the myocardium.. Among patients with ischemic cardiomyopathy, hibernating, but not ischemic, myocardium identifies which patients may accrue a survival benefit with revascularization versus medical therapy.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Female; Fluorodeoxyglucose F18; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Perfusion Imaging; Myocardial Revascularization; Myocardial Stunning; Myocardium; Patient Selection; Positron-Emission Tomography; Predictive Value of Tests; Propensity Score; Proportional Hazards Models; Radiopharmaceuticals; Recovery of Function; Risk Assessment; Risk Factors; Rubidium Radioisotopes; Stroke Volume; Time Factors; Tissue Survival; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Under experimental myocardial ischemia in rats of 10 months treatment with mildronate resulted in essential changes in metabolism of cardiomyocites. This includes stimulation of aerobic and anaerobic ways of power supply of heart cells: activation of glycolysis, oxidative phosphorylation and oxidative pyruvate decarboxylation with restoration of adenosine triphosphate pool to intact rats level in myocardium, serum and erythrocytes with signs of stabilization of cardiomyocytes membranes and essential decrease of tissue hypoxia. Introduction of mildronate to old rats (24 months) with an experimental myocardium ischemia was accompanied by lesser expressed changes of metabolism: activation of glycolysis and oxidative pyruvate decarboxylation without stimulation of Crebs' cycle enzymes. This became sufficient for restoration of adenosine triphosphate pool in myocardium without change of its quantity in serum and erythrocytes with signs of stabilization of cardiomyocytes membranes and moderate reduction of tissue hypoxia degree.

Topics: 2,3-Diphosphoglycerate; Adenosine Triphosphate; Age Factors; Animals; Cardiovascular Agents; Creatine Kinase; Decarboxylation; Energy Metabolism; Glycolysis; Isoenzymes; L-Lactate Dehydrogenase; Male; Methylhydrazines; Myocardial Ischemia; Myocytes, Cardiac; Pyruvates; Rats; Rats, Wistar

Coronary artery disease leading to myocardial ischemia is the most common cause of heart failure. Apelin (APLN), the endogenous peptide ligand of the APJ receptor, has emerged as a novel regulator of the cardiovascular system.. Here we show a critical role of APLN in myocardial infarction (MI) and ischemia-reperfusion (IR) injury in patients and animal models. Myocardial APLN levels were reduced in patients with ischemic heart failure. Loss of APLN increased MI-related mortality, infarct size, and inflammation with drastic reductions in prosurvival pathways resulting in greater systolic dysfunction and heart failure. APLN deficiency decreased vascular sprouting, impaired sprouting of human endothelial progenitor cells, and compromised in vivo myocardial angiogenesis. Lack of APLN enhanced susceptibility to ischemic injury and compromised functional recovery following ex vivo and in vivo IR injury. We designed and synthesized two novel APLN analogues resistant to angiotensin converting enzyme 2 cleavage and identified one analogue, which mimicked the function of APLN, to be markedly protective against ex vivo and in vivo myocardial IR injury linked to greater activation of survival pathways and promotion of angiogenesis.. APLN is a critical regulator of the myocardial response to infarction and ischemia and pharmacologically targeting this pathway is feasible and represents a new class of potential therapeutic agents.

Topics: Adipokines; Animals; Apelin; Cardiovascular Agents; Disease Models, Animal; Endothelial Cells; Heart Failure; Humans; Intercellular Signaling Peptides and Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Neovascularization, Physiologic; Peptides; Recovery of Function; Stem Cells; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

This paper presents the specific features of clinical manifestation and treatment of coronary heart disease (CHD) in the Russian Federation and compares them to the data from other countries participating in the international CLARIFY (ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) Registry. In accordance with the exclusion and inclusion criteria, 2249 patients from 43 Russian regions were included in the Registry. Russian patients were younger and had a higher prevalence of risk factors and comorbidities, compared to patients from other countries. In particular, the former more often had cardiovascular disease in family history, smoked (20.9% vs 11.8%; p<0.0001), and had dyslipidemia (77.8% vs 74.6%; p<0.0001) or hypertension (79.6% vs 70.3%; p<0.0001).They also had a higher heart rate (p<0.0001). ). While the incidence of myocardial infarction, based on medical history, was significantly higher than in patients from other countries (78.3% vs 58.4%; p<0.0001), percutaneous coronary intervention (PCI) was performed 2.5 times less often. Particularly striking differences were observed for the prevalence of stable angina and heart failure, which was, respectively, 4.0 and 7.8 times higher in Russian patients, despite the fact that the prescription frequency was similar in the Russian Federation and other countries. These findings should focus Russian doctors attention on the potential ways to solve the problem of "national features" in the treatment of stable CHD.

Topics: Cardiovascular Agents; Comorbidity; Female; Health Status Indicators; Humans; Incidence; Internationality; Male; Middle Aged; Myocardial Ischemia; Percutaneous Coronary Intervention; Registries; Risk Factors; Russia; Survival Analysis

Topics: Acute Coronary Syndrome; Aged, 80 and over; Aortic Diseases; Atherosclerosis; Calcinosis; Cardiovascular Agents; Colitis, Ischemic; Dietary Supplements; Humans; Hyperparathyroidism, Secondary; Hypertension; Hypotension; Kidney Failure, Chronic; Male; Myocardial Ischemia; Nephrosclerosis; Obesity; Parenteral Nutrition; Pneumatosis Cystoides Intestinalis; Renal Dialysis; Splanchnic Circulation

Topics: Cardiovascular Agents; Clopidogrel; Evidence-Based Medicine; Health Services Accessibility; Humans; Male; Middle Aged; Myocardial Ischemia; Poverty; Ramipril; Randomized Controlled Trials as Topic; Research Design; Simvastatin; Ticlopidine; Treatment Outcome

We prospectively applied the Surgical Treatment of Ischemic Cardiomyopathy trial entry criteria to an observational database to determine whether coronary artery bypass grafting (CABG) decreases mortality compared with medical therapy (MED) for patients with coronary artery disease and depressed left ventricular ejection fraction.. This was a retrospective, observational, cohort study of prospectively collected data from the Duke Databank for Cardiovascular Disease. Long-term mortality was the main outcome measure. Between January 1, 1995, and July 31, 2009, 86,874 patients underwent cardiac catheterization for suspected ischemic heart disease and were evaluated for inclusion in the analysis.. A total of 2,624 patients were found to have left ventricular ejection fraction less than 0.35, coronary artery disease amenable to CABG, and no left main stenosis of greater than 50%. After exclusions including ongoing Canadian Cardiovascular Society class III angina and acute myocardial infarction, 763 patients were included for propensity score analysis, including 624 who received MED and 139 who underwent CABG. Adjusted mortality curves were constructed for those patients in the three quintiles most likely to receive CABG. The curves diverged early, with risk-adjusted mortality rates at 5 years of 46% for MED versus 29% for CABG, and the survival benefit of CABG over MED continued through 10 years of follow-up (hazard ratio, 0.63; 95% confidence interval, 0.45 to 0.88).. Among a propensity-matched, risk-adjusted, observational cohort of patients with coronary artery disease, left ventricular ejection fraction less than 0.35, and no left main disease of greater than 50%, CABG is associated with a survival advantage over MED through 10 years of follow-up.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiac Catheterization; Cardiovascular Agents; Comorbidity; Coronary Artery Bypass; Databases, Factual; Female; Follow-Up Studies; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mitral Valve Insufficiency; Models, Cardiovascular; Myocardial Ischemia; North Carolina; Retrospective Studies; Risk Factors; Stroke Volume; Treatment Outcome

Coronary heart disease is the leading cause of death worldwide. In the United States, approximately 1 of every 6 deaths in 2007 was caused by coronary heart disease. Clinical presentation in the acute setting is mostly due to atherosclerotic plaque rupture leading to flow limitation in the affected vessel, and myocardial ischemia and infarction. ST-segment elevation myocardial infarction is usually associated with complete occlusion of the coronary artery and carries the worst prognosis in terms of in-hospital mortality. Despite various advances in treatment options, including percutaneous coronary intervention, ischemic heart disease still carries a significant morbidity and mortality. In this article, we aim to provide a summary of a few key advances in the management of ST-segment elevation myocardial infarction.

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Electrocardiography; Fibrinolysis; Hospital Mortality; Humans; Myocardial Infarction; Myocardial Ischemia; Stents

Topics: Absorbable Implants; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Everolimus; Humans; Myocardial Ischemia; Sirolimus; Tissue Scaffolds

This report contains authors own data about hyperglycemia impact on main functional properties of endothelial cells, mesenchymal stem cells and circulating progenitor cells, which define their participation in angiogenesis. Obtained data shows that cultivation of endothelial cells in hyperglycemic conditions leads to decrease of their ability for targeted migration and vascular-like structures formation on matrigel, and to suppression of VEGF receptors expression in these cells. Mesenchymal stem cells cultivated in hyperglycemic conditions have altered expression profile, decreased ability to stimulate angiogenesis via paracrine activity. Hyperglycemia in CHD patients with concomitant diabetes mellitus type II most probably lead to circulating bone marrow progenitor cells mobilisation distortion in response to tissue ischemia and damage to the endothelium, that can infringe upon their participation in endothelium reparation and angio- and vasculogenesis in the ischemic conditions. Found distortions can be used as targets for the treatment aimed at cardiovascular complications prevention in diabetic patients.

Topics: Bone Marrow Cells; Cardiovascular Agents; Cell Movement; Diabetes Mellitus; Drug Discovery; Endothelial Cells; Endothelium, Vascular; Humans; Hyperglycemia; Myocardial Ischemia; Neovascularization, Physiologic; Receptors, Vascular Endothelial Growth Factor; Secondary Prevention; Stem Cells

Topics: Cardiology; Cardiovascular Agents; Cardiovascular Diseases; Evidence-Based Medicine; Female; Humans; Myocardial Ischemia; Risk Factors; Sex Factors; Women's Health

The effect of 17-methoxyl-7-hydroxy-benzene-furanchalcone isolated from the roots of Millettia pulchra (Benth.) Kurz var. Laxior (Dunn) Z. Wei on rat myocardial ischemia has been investigated. An in vitro cardiocyte apoptosis model and an in vivo myocardial ischemia model were used to elucidate the mechanism of 17-methoxyl-7-hydroxy-benzene-furanchalcone. In contrast to hydrogen peroxide (H2O2, 100 µmol/L), 17-methoxyl-7-hydroxy-benzene-furanchalcone in vitro (255 and 510 µmol/L) increased the quantity of total superoxide dismutase and the protein expression of B cell lymphoma/leukemia-2, while it inhibited cardiocyte apoptosis, the release of malondialdehyde and tumor necrosis factor α, and protein expression of nuclear factor κ Bp65 and Bcl-2-associated X protein. Furthermore, pretreatment with MHBFC in vivo (10 and 20 mg/kg) decreased heart rate, systolic pressure, diastolic pressure, average pressure, left ventricular systolic pressure, the largest upstroke velocity of the left ventricular pressure (+ dp/dtmax), total antioxidative capability, myoglobin isoenzyme of creatine kinase, and inducible nitric oxide synthase, while it increased endothelial nitric oxide synthase, ATPases, left ventricular diastolic pressure, left ventricular end-diastolic pressure, the largest descendent velocity of the left ventricular pressure (-dp/dtmax) and the interval from the beginning of left ventricular contraction to +dp/dtmax (t - dp/dtmax), all in a dose-dependent manner. Our present results suggest that 17-methoxyl-7-hydroxy-benzene-furanchalcone is an attractive antimyocardial ischemia agent mostly because of its negative heart rate and negative inotropic effects, the reduction in myocardial oxidative damage, and the modulating expression of genes associated with apoptosis, which improves diastolic function.

Topics: Animals; Apoptosis; Cardiovascular Agents; Cells, Cultured; Chalcones; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Female; Hemodynamics; Male; Millettia; Myocardial Contraction; Myocardial Ischemia; Myocardium; Myocytes, Cardiac; Plant Roots; Rats; Rats, Sprague-Dawley; Superoxide Dismutase

To compare outcomes following intervention in dialysis-dependent patients with ischemic heart disease.. Ischemic heart disease is a major cause of mortality in dialysis-dependent patients. Coronary revascularization and medical modification to relieve symptoms is common, however, there is no clear consensus regarding optimal treatment.. Ninety dialysis-dependent patients with ischemic heart disease were prospectively assessed between 1999 and 2009, with a median follow-up of 24 months; 35 received best medical management, 31 had percutaneous coronary angioplasty and stenting, and 24 had coronary artery bypass grafting.. By multivariate analysis, higher body mass index and lower logistic EuroSCORE were associated with having either procedure compared to medical management. Using the time-to-event Kaplan-Meier method, both stenting and coronary bypass grafting had lower risks of an adverse outcome than best medical management. Mortality was 40/90 (44.4%). Multivariate predictors of mortality were smoking and a logistic EuroSCORE of 7-14. Overall mortality was not different among groups, however, the stent group had a survival advantage at 30-days and 1-year compared to the coronary bypass group. Composite median survival was 52.3 months. SF-36 questionnaires showed quality of life after bypass grafting was significantly better than medical management or stenting. Physical function was better after bypass grafting compared to medical management or stenting.. Dialysis-dependent patients with ischemic heart disease have poor survival despite intervention. Coronary artery bypass achieves fewer composite adverse events and better quality of life than stenting. Symptoms and coronary anatomy should dictate treatment decisions in dialysis-dependent patients.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Bypass; Female; Humans; Kaplan-Meier Estimate; Kidney Failure, Chronic; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Odds Ratio; Patient Selection; Proportional Hazards Models; Quality of Life; Queensland; Renal Dialysis; Retrospective Studies; Risk Assessment; Risk Factors; Stents; Time Factors; Treatment Outcome

The aim of this study was to evaluate the independent prognostic significance of ischemia change in stable coronary artery disease (CAD).. Recent randomized trials in stable CAD have suggested that revascularization does not improve outcomes compared with optimal medical therapy (MT). In contrast, the nuclear substudy of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial found that revascularization led to greater ischemia reduction and suggested that this may be associated with improved unadjusted outcomes. Thus, the effects of MT versus revascularization on ischemia change and its independent prognostic significance requires further investigation.. From the Duke Cardiovascular Disease and Nuclear Cardiology Databanks, 1,425 consecutive patients with angiographically documented CAD who underwent 2 serial myocardial perfusion single-photon emission computed tomography scans were identified. Ischemia change was calculated for patients undergoing MT alone, percutaneous coronary intervention, or coronary artery bypass grafting. Patients were followed for a median of 5.8 years after the second myocardial perfusion scan. Cox proportional hazards regression modeling was used to identify factors independently associated with the primary outcome of death or myocardial infarction (MI). Formal risk reclassification analyses were conducted to assess whether the addition of ischemia change to traditional predictors resulted in improved risk classification for death or MI.. More MT patients (15.6%) developed ≥5% ischemia worsening compared with those undergoing percutaneous coronary intervention (6.2%) or coronary artery bypass grafting (6.7%) (p < 0.001). After adjustment for established predictors, ≥5% ischemia worsening remained a significant independent predictor of death or MI (hazard ratio: 1.634; p = 0.0019) irrespective of treatment arm. Inclusion of ≥5% ischemia worsening in this model resulted in significant improvement in risk classification (net reclassification improvement: 4.6%, p = 0.0056) and model discrimination (integrated discrimination improvement: 0.0062, p = 0.0057).. In stable CAD, ischemia worsening is an independent predictor of death or MI, resulting in significantly improved risk reclassification when added to previously known predictors.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Bypass; Coronary Artery Disease; Databases, Factual; Disease Progression; Female; Humans; Kaplan-Meier Estimate; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Myocardial Ischemia; Myocardial Perfusion Imaging; North Carolina; Percutaneous Coronary Intervention; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Time Factors; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

We describe in this article a clinical case of a patient with arterial hypertension, painless myocardial ischemia and extensive constrictive atherosclerosis of coronary arteries. Coronary heart disease (painless ischemia) was suspected basing on results of transesophageal electrostimulation coupled with stress echocardiography and was confirmed by coronary angiography. This description is followed by discussion of possibilities of different instrumental methods in diagnostics of painless ischemia, classification of painless ischemia, treatment, and prognosis.

Topics: Angioplasty; Anticholesteremic Agents; Asymptomatic Diseases; Atorvastatin; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Drug-Eluting Stents; Echocardiography; Electrophysiologic Techniques, Cardiac; Exercise Test; Heptanoic Acids; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Myocardial Ischemia; Pyrroles; Severity of Illness Index; Treatment Outcome

Basic studies have shown a variety of ion channels are involved in the pathogenesis of ischemic heart disease, including L type Ca(2+) channel, T type Ca(2+) channel, ATP-sensitive potassium channel, If (funny) channel and late Na(+) channel. Clinical studies showed that the regulation of these channels function can improve myocardial blood supply and metabolism of myocardium. What is summarized below relates to the clinical usefulness of various ion channel antagonists reviewed by a clinical cardiologist, not a basic scientist working on ion channel biology.

Topics: Cardiovascular Agents; Humans; Ion Channels; Myocardial Ischemia

Purinergic receptors have attracted growing interest as therapeutic targets. This perspective focuses on P2X(4) receptors as a new cardioprotective target in heart failure.

Topics: Adenosine Triphosphate; Animals; Cardiovascular Agents; Heart Failure; Humans; Myocardial Ischemia; Myocardium; Purinergic P2X Receptor Agonists; Receptors, Purinergic P2X4; Signal Transduction

After 1970 the preexisting gap in population health between democratic Europe and communist countries became even more prominent. While in the democratic Europe there was a progressive rise in life expectancy associated with the decline in ischaemic heart disease (IHD), the trend on the other side of the iron curtain was exactly reverse. After the fall of communism in 1989 population health in the post-communist central Europe (CE) rapidly signalled a favourable recovery. This biphasic trend in post-communist countries is very remarkable. Most remarkably the decline in IHD mortality started soon after the demise of totality, even before the modernization of health care (new more effective medications and diagnostic technology), public campaign against smoking and improved supply of protective nutrients got chance to attain an important role. The decades-long psychosocial depression of communism was rapidly replaced with a promise of a better future. It is generally accepted that psychosocial factors are powerfool tools in the pathogenesis of IHD.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Diet; Europe, Eastern; Humans; Life Expectancy; Myocardial Ischemia

According to some data up to 20% of patients with thyrotoxicosis suffer from vasospastic angina. But presence of coronary artery spasm can be rarely confirmed. We describe a case of development of spasm of coronary arteries in a patients with severe thyrotoxicosis. Despite active treatment of thyrotoxicosis and use of drugs aimed at prevention of coronary spasm this patient with minor changes in coronary arteries (according to autopsy data) developed episode of acute myocardial ischemia leading to lethal outcome. This clinical case shows that patients with thyrotoxicosis and documented transitory myocardial ischemia should receive therapy with thyrostatics and drugs preventing coronary spasm in maximal doses until stable normalization of levels of thyroid hormones.

Topics: Antithyroid Agents; Atrial Fibrillation; Cardiovascular Agents; Coronary Angiography; Electrocardiography; Fatal Outcome; Heart Failure; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardium; Thyrotoxicosis

Patients with ischemic heart disease and depressed left ventricular (LV) ejection fraction (LVEF) develop varying degrees of LV remodeling after cardiac surgical revascularization. Fifty-three patients with stable ischemic heart disease and impaired LV function (LVEF 34.9 ± 4%) were prospectively followed up for 24 months. Thirty-seven patients underwent coronary artery bypass grafting (CABG), 16 patients were treated conservatively. Cardiac magnetic resonance imaging (MRI) and SPECT were performed at baseline and after 12 and 24 months of follow-up. The patients were divided into responders and non-responders depending on the degree of LVEF improvement at 24 months follow-up (>5%-responders). MRI with ≤5 segments with DE/wall thickness ratio (DEWTR) ≥50% predicted LV reverse remodeling with a sensitivity of 86% and a specificity of 75% (AUC 0.81). An MRI finding of ≤2 segments with the DEWTR ≥75% had a corresponding sensitivity of 71% and specificity of 67% (AUC 0.75) while fixed perfusion defect on SPECT <16.5% of LV predicted reverse remodeling with a sensitivity of 64% and a specificity of 69% (AUC 0.64). A preoperative number of segments with the DE/wall thickness ratio of ≥50 and ≥75% obtained by MRI, was found to be a better predictor of left ventricular reverse remodeling than fixed perfusion defect by SPECT. No other MRI or SPECT parameter predicted LVEF improvement at 24 months after CABG.

Topics: Aged; Aged, 80 and over; Cardiomyopathies; Cardiovascular Agents; Coronary Angiography; Coronary Artery Bypass; Czech Republic; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Myocardial Ischemia; Predictive Value of Tests; Prospective Studies; Recovery of Function; Stroke Volume; Time Factors; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling

The protective effects of cyclic dipeptides in alcoholic beverages were investigated in the perfused guinea-pig hearts subjected to ischemia and reperfusion. Subsequently, in order to determine the importance of cyclic dipeptide structure, the effects of cyclo(L-Leu-L-Tyr) (cLY) were compared with those of the newly synthesized non-cyclic dipeptides, L-Leu-L-Tyr (LY) and L-Tyr-L-Leu (YL). After reperfusion, pressure recovery (%) in the left ventricle reached a peak of over 90% in the presence of cLY (10(-6) M and 10(-5) M) (control: 22.9%). The recovery by LY and YL was significantly lower than that by cLY, and ATP levels simultaneously monitored using (31)P-NMR were already lower during the ischemic end period than those observed with cLY treatment. In perfused mitochondrial preparations, cLY significantly inhibited mitochondrial Ca(2+) ([Ca(2+)](m)) elevation in a similar way to that of the mitochondrial permeability transition pore (MPTP) inhibitor cyclosporin A. In vitro electron paramagnetic resonance (EPR) revealed that the active oxygen radicals quenching activity of cLY was greater than those of non-cyclic dipeptides. cLY inhibited caspase-3-induced apoptosis. The cyclic dipeptide structure inhibits opening of the MPTP by preventing [Ca(2+)](m) overload-induced apoptosis related to mitochondrial active oxygen radical accumulation in ischemia-reperfusion hearts.

Topics: Adenosine Triphosphate; Animals; Antioxidants; Apoptosis; Calcium; Cardiovascular Agents; Caspase 3; Cyclosporine; Dipeptides; Female; Guinea Pigs; Male; Mitochondria; Mitochondrial Membrane Transport Proteins; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Peptides, Cyclic; Structure-Activity Relationship; Ventricular Dysfunction, Left

Spontaneous coronary artery dissection (SCAD) is a rare cause of chest pain and cardiomyopathy. This phenomenon usually occurs during the peripartum period. SCAD associated with exercise and heavy weight lifting is even rarer and has been reported in less than 10 cases in the literature. We describe a case of SCAD associated with heavy weight lifting and exercise in a 29-year-old male who presented with exertional chest pain. The patient subsequently underwent a cardiac catheterization that showed a left ventricular ejection fraction of 40% and a dissection in the left anterior descending (LAD) coronary artery after the first diagonal/septal branch with extension to the distal LAD that wrapped around the apex. He was effectively managed with the combination of medical therapy followed by a few days later with stenting. In summary, diagnosis and treatment of this rare phenomenon is a challenge, but early diagnosis and appropriate management can lead to a successful outcome.

Topics: Adult; Angina Pectoris; Angioplasty, Balloon, Coronary; Aortic Dissection; Cardiac Catheterization; Cardiomyopathies; Cardiovascular Agents; Coronary Aneurysm; Electrocardiography; Humans; Male; Myocardial Ischemia; Stents; Stroke Volume; Treatment Outcome; Ventricular Function, Left; Weight Lifting

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Comparative Effectiveness Research; Cross-Cultural Comparison; Diabetes Mellitus, Type 2; Effect Modifier, Epidemiologic; Europe; Female; Health Services Accessibility; Humans; Hyperlipidemias; Hypolipidemic Agents; International Cooperation; Male; Middle Aged; Monitoring, Physiologic; Myocardial Ischemia; Patient Compliance; Physical Fitness; Risk Factors; Secondary Prevention; Smoking

Although hypoxia and ischemia are known to be involved in the pathogenesis of cardiovascular disease, specific therapeutic targets still remain elusive. To address this important issue, we have performed 2 series of experimental studies, aiming at erythropoietin (Epo)/Epo receptor (EpoR) based on the following backgrounds. Epo has long been regarded as a hematopoietic hormone that acts exclusively in the proliferation and differentiation of erythroid progenitors. Although recent studies have demonstrated that EpoR is expressed in the cardiovascular system, the potential protective role of the vascular Epo/EpoR system in vivo remains to be examined. We hypothesized that the vascular Epo/EpoR system plays an important protective role against the development of cardiovascular disease. Using vascular EpoR-deficient mouse, we demonstrated that the vascular Epo/EpoR system plays a crucial role for endothelial function and vascular homeostasis. The vascular Epo/EpoR system is important for the activation of the vascular endothelial growth factor/vascular endothelial growth factor receptor-2 system, inhibits hypoxia-induced pulmonary endothelial damage and promotes ischemia-induced angiogenesis in vivo. These results indicate that the vascular Epo/EpoR system plays an important protective role against hypoxia/ischemia, demonstrating that this system is a novel therapeutic target in cardiovascular medicine.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Drug Delivery Systems; Endothelium, Vascular; Erythropoietin; Homeostasis; Humans; Hypoxia; Mice; Mice, Knockout; Myocardial Ischemia; Receptors, Erythropoietin

Carthamus tinctorius injection (CTI) is a traditional Chinese medicine (TCM) specifically used for the treatment of cerebral ischemia and myocardial ischemia.. This study evaluated the protective effects of CTI on isoprenaline-induced acute myocardial ischemia (AMI) in rats and explored the underlying mechanisms.. (i) Sprague-Dawley rats were randomly divided into 5 groups: control, myocardial ischemia model, and high-, low-dose of CTI groups (2.5 and 0.625 g/kg, respectively, i.p. for 5 days), and Xiang-Dan (20 g/kg) group (n = 10 in each group). AMI was induced by isoproterenol (5 mg/kg) by intraperitoneal injection. Assessment of electrocardiograms (ECG) was carried out. (ii) Another 40 rats were randomly divided into 5 groups, the concentration of IL-6 and TNF-α in serum were measured by radioimmunological assay; Bcl-2 and Bax protein expression were measured by immunohistochemistry.. CTI (2.5 and 0.625 g/kg) significantly inhibited the typical ECG S-T segment elevation, reduced concentration of IL-6 and TNF-α in serum, suppressed overexpression of Bax protein and also inhibited the reduction of Bcl-2 expression and markedly depressed the Bax/Bcl-2 ratio.. These findings demonstrate that CTI is cardioprotective against AMI in rats and is likely to related to decrease inflammatory response mediated by TNF-α and IL-6, down-regulate protein level of Bax and up-regulate that of Bcl-2 in the heart tissue.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Cardiovascular Agents; Carthamus tinctorius; Disease Models, Animal; Drugs, Chinese Herbal; Electrocardiography; Female; Inflammation Mediators; Injections, Intraperitoneal; Interleukin-6; Isoproterenol; Male; Myocardial Ischemia; Myocardium; Plant Preparations; Plants, Medicinal; Protective Agents; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Time Factors; Tumor Necrosis Factor-alpha

Treatment of patients with hypertension and ischemic heart disease should be focused not only on the control of overall cardiovascular risk factors, particularly blood pressure, but also on eliminating anginal symptoms, or at least reducing them, as angina symptoms have a crucial prognostic value. Although the amount of blood pressure reduction, rather than the choice of antihypertensive drug, is the major determinant of reduction of cardiovascular risk, some drugs such as ?-blockers should be preferably used in patients with angina. However, ?-blockers are contraindicated or produce intolerable side effects in many patients. Although, in the last years, new drugs for the treatment of stable angina have emerged, diltiazem should remain as a good alternative in the treatment of these patients. In this article, available evidence regarding diltiazem in the treatment of hypertension and ischemic heart disease is updated.

Topics: Antihypertensive Agents; Blood Pressure; Cardiovascular Agents; Cardiovascular Diseases; Diltiazem; Humans; Hypertension; Myocardial Ischemia; Risk Factors

This study aimed to determine persistence, adherence, and time without therapy with cardiovascular medicines over all episodes of use among veterans following hospitalization for ischemic heart disease.. Retrospective cohort study using Department of Veterans' Affairs database including 9635 veterans with a hospitalization for acute myocardial infarction, angina, or ischemic heart disease, and who had been dispensed cardiovascular medicines in the 3 months posthospitalization. The main outcome measures were duration of first treatment episode, duration of overall treatment episode, and adherence with recommended therapies: angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), lipid-lowering therapy, calcium channel blockers (CCBs), beta-blockers, and antiplatelet therapy.. The median duration of overall treatment was 6.2 years [95% confidence interval (CI): 6.0-6.4] for lipid-lowering therapy, 5.4 years (95% CI: 5.1-5.5) for ACE inhibitors/ARBs, 5.0 years (95% CI: 4.8-5.1) for antiplatelets, 3.4 years (95% CI: 3.3-3.6) for beta-blockers, and 2.8 years (95% CI: 2.6-3.0) for CCBs. Adherence was 72% for CCBs, 75% for ACE inhibitors/ARBs, 84% for lipid-lowering therapy, and 84% for antiplatelets other than aspirin. The median time without therapy was 4.5 months or less for ACE inhibitors/ARBs, antiplatelets, and lipid-lowering therapy.. Problems with medication adherence can relate to either persistence or compliance during treatment. This novel method provides a way to determine which of these factors is most problematic when considering chronic therapies. We found that Australian veterans with established cardiovascular disease are persistent with their cardiovascular therapy, with only small gaps in therapy.

Topics: Aged; Aged, 80 and over; Australia; Cardiovascular Agents; Drug Prescriptions; Female; Humans; Male; Medication Adherence; Myocardial Ischemia; Retrospective Studies; Time Factors; Veterans

Topics: Cardiovascular Agents; Humans; Myocardial Ischemia; Perhexiline; Treatment Failure

The American Heart Association (AHA) Scientific Sessions 2009 meeting held in Orlando, FL, USA included topics covering new treatments for cardiovascular disease. This conference report highlights selected presentations on stem cell treatments for ischemia, treatments for hypertension and atherosclerosis, and LDL-lowering compounds.

Topics: Anticholesteremic Agents; Atherosclerosis; Cardiovascular Agents; Cardiovascular Diseases; Cholesterol, LDL; Humans; Hypertension; Myocardial Ischemia; Stem Cell Transplantation

Myocardial ischemia (MI) is a worldwide epidemic. Compound Danshen Tablets (CDTs), an herbal compound preparation, are widely used to treat MI in China. In this study, we aimed to explore novel biomarkers to increase the understanding of MI and investigate therapeutic mechanisms of CDT by using a metabolomic approach. Plasma extracts from sham, MI model, CDT- and western medicines (isosorbide dinitrate, verapamil, propranolol, captopril, and trimethazine)-treated rats were analyzed by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The orthogonal partial least square (OPLS) model was built to find metabolites expressed in significantly different amounts between MI and sham rats. Meanwhile, partial least squares discriminant analysis (PLS-DA) was used to investigate CDT's protective effects. The results showed that CDT presented protective effects on MI by reversing potential biomarkers to sham levels, especially for the four metabolites in the pathway of purine metabolism (hypoxanthine, xanthine, inosine and allantoin).

Topics: Allantoin; Animals; Biomarkers; Cardiovascular Agents; Chromatography, Liquid; Disease Models, Animal; Drugs, Chinese Herbal; Hypoxanthine; Inosine; Least-Squares Analysis; Male; Metabolomics; Myocardial Ischemia; Principal Component Analysis; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Salvia miltiorrhiza; Spectrometry, Mass, Electrospray Ionization; Tablets; Xanthine

To investigate the involvement of reactive oxidant species (ROS), presumably arising from cytochrome P-450 (CYP)-catalyzed metabolism of schisandrin B (Sch B), in triggering glutathione antioxidant response, Sch B induced reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent and CYP-catalyzed reaction and associated ROS production were examined in rat heart microsomes. Sch B analogs were also studied for comparison. Using rat heart microsomes as a source of CYP, Sch B and schisandrin C (Sch C), but not schisandrin A and dimethyl diphenyl bicarboxylate (an intermediate compound derived from the synthesis of Sch C), were found to serve as co-substrate for the CYP-catalyzed NADPH oxidation reaction, with concomitant production of ROS. The stimulation of CYP-catalyzed NADPH oxidation reaction and/or ROS production by Sch B or Sch C correlated with the increase in mitochondrial reduced glutathione level and protection against ischemia/reperfusion (I/R) injury in rat hearts. The involvement of ROS in Sch B-induced cardioprotection was further confirmed by the suppressive effect produced by N-acetylcysteine or alpha-tocopherol pretreatment. Taken together, these results suggest that Sch B-induced glutathione antioxidant response and cardioprotection may be mediated by ROS arising from CYP-catalyzed reaction.

Topics: Acetylcysteine; alpha-Tocopherol; Animals; Antioxidants; Cardiovascular Agents; Cyclooctanes; Cytochrome P-450 Enzyme System; Drugs, Chinese Herbal; Female; Glutathione; Lignans; Microsomes; Mitochondria; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; NADP; Oxidation-Reduction; Phytotherapy; Polycyclic Compounds; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Schisandra

A 77-year-old woman was referred to our Department of Cardiology because of exacerbation of chest pain and decreased exercise intolerance. No acute ischemic electrocardiography changes were seen in an electrocardiogram recorded on admission. An exercise test was terminated at 7 METS because of shortness of breath without evidence of ischemia. The patient was referred for a coronary angiography which showed a coronary artery fistula filling from the left anterior descending (LAD) artery and resulting in a large inflow to the main pulmonary artery, without other significant coronary lesions. Transthoracic echocardiography showed a coronary artery fistula draining to the main pulmonary artery. Coronary steal was suspected and coronary flow reserve was evaluated in LAD, showing normal values for age. Due to the overall clinical picture, with the predominance of heart failure symptoms and the lack of significant abnormalities of flow reserve in LAD, medical therapy was selected. The patient remained free from cardiovascular symptoms at 6-month follow-up.

Topics: Aged; Angina Pectoris; Arterio-Arterial Fistula; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Circulation; Echocardiography, Doppler; Electrocardiography; Exercise Test; Exercise Tolerance; Female; Humans; Myocardial Ischemia; Predictive Value of Tests; Pulmonary Artery

To investigate the cardioprotective potential of Syringa pinnatifolia Hems1. var. alashanensis essential oil (SPEO) against experimental acute myocardial ischemia (AMI), hydrogen peroxide (H(2)O(2))-induced myocyte injury and activities against hypoxia and platelet aggregation.. Wistar rats, Kunming mice and primary cultured rat neonatal myocytes were used in this study. AMI in rats was induced by ligation of the left anterior descending (LAD) coronary artery, and deviation of ST-segment, as well as changes of myocardial enzyme activities were observed. Hypoxia test in Kunming mice was performed to evaluate the effect of SPEO against hypoxia. The protective effect of SPEO on H(2)O(2)-induced cell injury was evaluated in terms of cell viability assay. The in vitro effect of SPEO against platelet aggregation was studied using adenosine 5'-diphosphate (ADP) as agonist.. Administration of SPEO reduced deviation of ST-segment, decreased the levels of lactate dehydrogenase (LDH), creatine kinase (CK) and Troponin T (TnT) while increased the activities of superoxide dismutase (SOD). The protective role of SPEO was further confirmed by histopathological examination. In the hypoxia test, both 8 and 32 mg/kg of SPEO could prolong survival time of mice under hypoxia condition. At the meantime SPEO showed remarkable protective effect on cultured rat myocyte death induced by H(2)O(2). SPEO also inhibited ADP-induced rat platelet aggregation by 47.4%, 37.0% and 32.9% at the dose of 5, 2.5 and 1.25 microg/mL, respectively.. These results suggest that SPEO possessing activities against hypoxia, oxidative stress and platelet aggregation has a significant protective effect against experimental myocardial ischemia.

Topics: Animals; Cardiovascular Agents; Cell Death; Creatine Kinase; Disease Models, Animal; Electrocardiography; Female; Hydrogen Peroxide; Hypoxia; L-Lactate Dehydrogenase; Male; Mice; Mice, Inbred Strains; Muscle Cells; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Oils, Volatile; Phytotherapy; Plant Extracts; Plant Stems; Platelet Aggregation; Rats; Rats, Wistar; Superoxide Dismutase; Syringa; Troponin T

Ischemic heart disease (IHD) is the leading cause of death worldwide. Novel cardioprotective strategies are therefore required to improve clinical outcomes in patients with IHD. Although a large number of novel cardioprotective strategies have been discovered in the research laboratory, their translation to the clinical setting has been largely disappointing. The reason for this failure can be attributed to a number of factors including the inadequacy of the animal ischemia-reperfusion injury models used in the preclinical cardioprotection studies and the inappropriate design and execution of the clinical cardioprotection studies. This important issue was the main topic of discussion of the UCL-Hatter Cardiovascular Institute 6th International Cardioprotection Workshop, the outcome of which has been published in this article as the "Hatter Workshop Recommendations". These have been proposed to provide guidance on the design and execution of both preclinical and clinical cardioprotection studies in order to facilitate the translation of future novel cardioprotective strategies for patient benefit.

Topics: Age Factors; Animals; Cardiovascular Agents; Disease Models, Animal; Humans; Ischemic Postconditioning; Ischemic Preconditioning, Myocardial; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Sex Factors; Species Specificity; Translational Research, Biomedical; Treatment Outcome

The cardioprotective property of Spondias mombin (SM) was investigated and compared with that of the ACE inhibitor, ramipril. Alterations to markers of myocardial injury and indices of antioxidant capacity by isoproterenol (ISP) intoxication were significantly corrected in groups treated with SM. The inflammatory index was increased by 24% in ISP-intoxicated group compared with control (P < 0.001) but reduced in the groups administered ISP and treated with 100 or 250 mg/kg SM by 17% (P < 0.001) and 11% (P < 0.05) respectively. Serum lactate dehydrogenase activity and cholesterol level which were significantly increased in ISP-intoxicated group compared with control were reduced in groups administered ISP and treated with SM. Serum phosphate levels in groups administered ISP and treated with SM were significantly lower than values obtained for the ISP-intoxicated group (P < 0.001). Tissue catalase and superoxide dismutase activities as well as glutathione level were significantly increased in groups administered ISP and treated with SM compared to ISP-intoxicated group while MDA and nitrite levels were decreased. Disruption in the structure of cardiac myofibrils by ISP intoxication was reduced by treatment with SM. Comparable results were obtained for ramipril. These results are indicative of the potent cardioprotective property of SM.

Topics: Anacardiaceae; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiovascular Agents; Catalase; Cholesterol; Disease Models, Animal; Dose-Response Relationship, Drug; Glutathione; Isoproterenol; L-Lactate Dehydrogenase; Male; Malondialdehyde; Myocardial Infarction; Myocardial Ischemia; Myocardium; Nitrites; No-Reflow Phenomenon; Phosphates; Plant Extracts; Plant Leaves; Ramipril; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Time Factors

The prognostic role of rest-redistribution 201-Thallium imaging has not been extensively investigated in patients with left ventricular ischemic dysfunction.. The aim of this study was to evaluate the ability of rest-redistribution 201-Thallium single photon emission computed tomography to predict cardiac death and occurrence of acute myocardial infarction in patients with ischemic mild-to-moderate left ventricular dysfunction.. One-hundred and twenty-six patients with chronic coronary artery disease and mean left ventricular ejection fraction 39 +/- 11% were followed-up for 30 +/- 17 months after a rest-redistribution 201-Thallium imaging single photon emission computed tomography. Cardiac death and acute myocardial infarction were considered as major cardiac events.. During the follow up, 11 (9%) cardiac deaths and 9 (7%) acute myocardial infarctions occurred. The only variable showing significant difference between patients with and without events was the number of severe irreversible defects (1.7 +/- 1.9 versus 0.9 +/- 1.2, respectively; P = 0.02). By Kaplan-Meier analysis, the presence of three or less, or more than three severe defects was selected as the best cutoff to identify patients with longer event-free survival from cardiac death or acute myocardial infarction (log rank 19.84; P < 0.0001). When only cardiac death was considered as clinical event, the presence of at least two severe defects best separated patients who died from those who survived (log rank 8.68; P = 0.0032).. Rest-redistribution 201-Thallium single photon emission computed tomography provides prognostic information in coronary patients with mild-to-moderate left ventricular dysfunction. The number of severe irreversible defects per patient is a powerful predictor of prognosis.

Topics: Aged; Cardiovascular Agents; Chronic Disease; Coronary Angiography; Coronary Artery Disease; Disease-Free Survival; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Myocardial Revascularization; Predictive Value of Tests; Prospective Studies; Risk Assessment; Severity of Illness Index; Thallium Radioisotopes; Time Factors; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Ventricular Dysfunction, Left

Myocardial fatty acid (FA) oxidation is regulated acutely by the FA supply and chronically at the transcriptional level owing to FA activation of peroxisome proliferator-activated receptor-alpha (PPARalpha). However, in vivo administration of PPARalpha ligands has not been shown to increase cardiac FA oxidation. In this study we have examined the cardiac response to in vivo administration of tetradecylthioacetic acid (TTA, 0.5% w/w added to the diet for 8 days), a PPAR agonist with primarily PPARalpha activity.. Despite the fact that TTA treatment decreased plasma concentrations of lipids [FA and triacylglycerols (TG)], hearts from TTA-treated mice showed increased mRNA expression of PPARalpha target genes. Cardiac substrate utilization, ventricular function, cardiac efficiency, and susceptibility to ischaemia-reperfusion were examined in isolated perfused hearts. In accordance with the mRNA changes, myocardial FA oxidation was increased 2.5-fold with a concomitant reduction in glucose oxidation. This increase in FA oxidation was abolished in PPARalpha-null mice. Thus, it appears that the metabolic effects of TTA on the heart must be owing to a direct stimulatory effect on cardiac PPARalpha. Hearts from TTA-treated mice also showed a marked reduction in cardiac efficiency (because of a two-fold increase in unloaded myocardial oxygen consumption) and decreased recovery of ventricular contractile function following low-flow ischaemia.. This study for the first time observed that in vivo administration of a synthetic PPARalpha ligand elevated FA oxidation, an effect that was also associated with decreased cardiac efficiency and reduced post-ischaemic functional recovery.

Topics: Administration, Oral; Animals; Blood Glucose; Cardiovascular Agents; Disease Models, Animal; Energy Metabolism; Fatty Acids; Gene Expression Regulation; Liver; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Myocardial Contraction; Myocardial Ischemia; Myocardium; Oxidation-Reduction; Oxygen Consumption; PPAR alpha; Recovery of Function; RNA, Messenger; Sulfides; Triglycerides; Ventricular Function

A new fluorenone alkaloid (caulophine) was isolated from the radix of Caulophyllum robustum Maxim. (collected from the Qinling mountains) using cell membrane chromatography as the screening method. Caulophine was identified as 3-(2-(dimethylamino)ethyl)-4,5-dihydroxy-1,6-dimethoxy-9H-fluoren-9-one based on physicochemic and spectroscopic analyses, particularly by NMR spectroscopic data (i.e., COSY, HMQC, HMBC, NOESY). Caulophine possessed anti-myocardial ischemia activity.

Topics: Alkaloids; Animals; Cardiovascular Agents; Caulophyllum; Chromatography; Disease Models, Animal; Fluorenes; Magnetic Resonance Spectroscopy; Male; Molecular Structure; Myocardial Infarction; Myocardial Ischemia; Rats; Rats, Sprague-Dawley

Mildronate [3-(2,2,2-trimethylhydrazinium) propionate] is an anti-ischaemic drug whose mechanism of action is based on its inhibition of L-carnitine biosynthesis and uptake. As L-carnitine plays a pivotal role in the balanced metabolism of fatty acids and carbohydrates, this study was carried out to investigate whether long-term mildronate treatment could influence glucose levels and prevent diabetic complications in an experimental model of type 2 diabetes in Goto-Kakizaki (GK) rats.. GK rats were treated orally with mildronate at doses of 100 and 200 mg.kg(-1) daily for 8 weeks. Plasma metabolites reflecting glucose and lipids, as well as fructosamine and beta-hydroxybutyrate, were assessed. L-carnitine concentrations were measured by ultra performance liquid chromatography with tandem mass spectrometry. An isolated rat heart ischaemia-reperfusion model was used to investigate possible cardioprotective effects. Pain sensitivity was measured with a tail-flick latency test.. Mildronate treatment significantly decreased L-carnitine concentrations in rat plasma and gradually decreased both the fed- and fasted-state blood glucose. Mildronate strongly inhibited fructosamine accumulation and loss of pain sensitivity and also ameliorated the enhanced contractile responsiveness of GK rat aortic rings to phenylephrine. In addition, in mildronate-treated hearts, the necrosis zone following coronary occlusion was significantly decreased by 30%.. These results demonstrate for the first time that in GK rats, an experimental model of type 2 diabetes, mildronate decreased L-carnitine contents and exhibited cardioprotective effects, decreased blood glucose concentrations and prevented the loss of pain sensitivity. These findings indicate that mildronate treatment could be beneficial in diabetes patients with cardiovascular problems.

Topics: 3-Hydroxybutyric Acid; Administration, Oral; Animals; Blood Glucose; Cardiovascular Agents; Carnitine; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Disease Models, Animal; Fructosamine; Heart; Hyperalgesia; Hypoglycemic Agents; In Vitro Techniques; Lipids; Male; Methylhydrazines; Myocardial Ischemia; Pain Threshold; Rats; Rats, Wistar

Severe and extensive coronary artery disease is the underlying cause of stress-induced wall motion abnormalities (SWMA) with low-dose (10 microg/kg/min) dobutamine suggesting that these abnormalities may identify those with poor outcome.. We assessed the prognostic value of low-dose SWMA in medically treated patients with ischemic cardiomyopathy.. Low- and peak-dose dobutamine echocardiography was performed in 235 patients with ischemic cardiomyopathy (ejection fraction 31% +/- 8%) who were treated with medical therapy. The survival of patients with low-dose SWMA (n = 33) was compared with the survival of patients without ischemia (n = 85) and those with peak-dose SWMA (n = 117).. There were 123 cardiac deaths (52%) during follow-up of 4.1 +/- 3.3 years. Multivariate predictors of cardiac death were age (p = 0.002, hazard ratio [HR]: 1.03), diabetes (p = 0.028, HR: 1.54), New York Heart Association (NYHA) class III, IV heart failure (p = 0.001, HR: 1.94), the presence of peak dose SWMA (p < 0.001, HR: 2.59), and low-dose SWMA (p = 0.005, HR: 2.28). Survival of patients without ischemia was significantly better than those with peak-dose SWMA (p < 0.0001) and those with low-dose SWMA (p = 0.001). The survival of patients with low-dose SWMA was the same as those with peak-dose SWMA (p = 0.89).. Low-dose SWMA is an independent predictor of cardiac mortality in medically treated patients with ischemic cardiomyopathy. Patients with low-dose SWMA are at equivalent risk to those with peak-dose SWMA.

Topics: Aged; Cardiomyopathies; Cardiovascular Agents; Dobutamine; Echocardiography, Stress; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Predictive Value of Tests; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left

The aim of this study was to investigate the long-term prognosis of non-interventionally followed patients with myocardial bridge and angiographic milking of the left anterior descending (LAD) coronary artery.. All of the coronary angiography records from May 2000 to November 2007 were reevaluated and patients who had more than 70% narrowing during systole on LAD were eligible for the present study. Follow-up was carried out by physical examination, echocardiography, and treadmill exercise testing. The clinical situations of the patients, medical treatment at the time of follow-up, and experienced events (death, myocardial infarction, or revascularization) were recorded.. There were 59 eligible patients (44 male, 74.6%). The mean age of the patients was 54 +/- 11 years. The bridges were located in the proximal, mid, and distal portion of the LAD in 17 (28.8%), 20 (33.9%), and 22 (37.3%) patients, respectively. Distributions of the narrowing degree were as follows: between 70% to 89% in 33 (56%) patients and 90% to 100% in 26 (44%) patients. Mean follow-up duration of the group was 37 +/- 13 months (range 15-65 mo). The clinical presentation during follow-up was stable angina in 9 (15.3%) cases, atypical angina in 12 (20.3%), atypical chest pain in 13 (22%), dyspnea in 3 (5.1%), and syncope in 3 (5.1%) cases. There were no experienced events and/or hospitalizations related to cardiac disease. Echocardiographic examination revealed normal systolic ventricular function. Only 17 (28.8%) patients continued to use medication. Most of them were on beta-blocker therapy.. Patients with myocardial bridges and angiographic milking of the LAD coronary artery have a good long-term prognosis.

Topics: Adult; Aged; Angina Pectoris; Cardiovascular Agents; Cineangiography; Coronary Angiography; Coronary Stenosis; Dyspnea; Echocardiography; Exercise Test; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Bridging; Myocardial Ischemia; Registries; Severity of Illness Index; Syncope; Time Factors; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Bypass; Diabetes Mellitus, Type 2; Humans; Information Dissemination; Myocardial Ischemia; Patient Selection; Randomized Controlled Trials as Topic; Research Design; Risk Assessment; Severity of Illness Index; Treatment Outcome

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Bypass; Coronary Artery Disease; Humans; Myocardial Ischemia

The anti-anginal drug Ranolazine, a partial fatty acid oxidation (pFOX) inhibitor, is thought to modulate the metabolism during myocardial ischemia by activating pyruvate dehydrogenase activity to promote glucose oxidation. Ranolazine and its five principal metabolites: CVT-2512, CVT-2513, CVT-2514, CVT-2738 and CVT-4786, were synthesized. The effect of Ranolazine and its metabolites on the ECG (electrocardiogram) of mice with myocardial ischemia induced by isoprenaline and their effect on alleviating the symptom of myocardial ischemia were tested and compared. The results showed that CVT-2738 and CVT-2513 could be protective against mice myocardial ischemia induced by isoprenaline. Within all the metabolites tested in this study, CVT-2738 exhibited the best potency, however, it was still less potent than Ranolazine.

Topics: Acetanilides; Animals; Cardiovascular Agents; Drug Evaluation, Preclinical; Electrocardiography; Female; Glucose; Isoproterenol; Male; Mice; Mice, Inbred Strains; Myocardial Ischemia; Oxidation-Reduction; Piperazines; Ranolazine

Topics: Acetanilides; Angina Pectoris; Cardiovascular Agents; Coronary Artery Disease; Coronary Circulation; Exercise Test; Humans; Myocardial Ischemia; Myocardial Perfusion Imaging; Oxygen Consumption; Piperazines; Ranolazine; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon; Treatment Outcome

Patients with peripheral arterial disease constitute a high-risk population. Guideline-recommended medical therapy use is therefore of utmost importance. The aims of our study were to establish the patterns of guideline-recommended medication use in patients with PAD at the time of vascular surgery and after 3 years of follow up, and to evaluate the effect of these therapies on long-term mortality in this patient group.. Data on 711 consecutive patients with peripheral arterial disease undergoing vascular surgery were collected from 11 hospitals in the Netherlands (enrollment between May and December 2004). After 3.1+/-0.1 years of follow-up, information on medication use was obtained by a questionnaire (n=465; 84% response rate among survivors). Guideline-recommended medical therapy use for the combination of aspirin and statins in all patients and beta-blockers in patients with ischemic heart disease was 41% in the perioperative period. The use of perioperative evidence-based medication was associated with a reduction of 3-year mortality after adjustment for clinical characteristics (hazard ratio, 0.65; 95% CI, 0.45 to 0.94). After 3 years of follow-up, aspirin was used in 74%, statins in 69%, and beta-blockers in 54% of the patients respectively. Guideline-recommended medical therapy use for the combination of aspirin, statins, and beta-blockers was 50%.. The use of guideline recommended therapies in the perioperative period was associated with reduction in long-term mortality in patients with peripheral arterial disease. However, the proportion of patients receiving these evidence-based treatments-both at baseline and 3 years after vascular surgery-was lower than expected based on the current guidelines. These data highlight a clear opportunity to improve the quality of care in this high-risk group of patients.

Topics: Adrenergic beta-Antagonists; Aged; Aspirin; Cardiovascular Agents; Drug Therapy, Combination; Evidence-Based Medicine; Female; Follow-Up Studies; Guideline Adherence; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Myocardial Ischemia; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prognosis; Registries; Risk Factors

In the ABSORB trial, the feasibility of using a fully bioabsorbable everolimus-eluting stent (BVS; Abbott Vascular, Santa Clara, CA) in patients with ischemia and a single de novo coronary lesion was investigated. Some important concerns about the efficacy of this device were raised by this study. The in-stent late loss with the BVS (0.44 mm) was comparable to that seen with some drug-eluting stents currently on the market, and the late lumen loss was primarily due to reduction in stent area. Technical improvements aimed at definitively preventing late vessel recoil and negative remodeling, as well as clarification of the behavior of these devices with longer follow-up, are needed before fully bioabsorbable drug-eluting stents can be considered a therapeutic option for patients with coronary artery disease.

Topics: Absorbable Implants; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Clinical Trials as Topic; Coronary Artery Disease; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Humans; Myocardial Ischemia; Prosthesis Design; Research Design; Sirolimus; Treatment Outcome

Females demonstrate improved cardiac recovery after ischemia/reperfusion injury compared with males. Attenuation of myocardial dysfunction with preischemic estradiol suggests that estrogen may be an important mediator of this cardioprotection. However, it remains unclear whether post-injury estradiol may have clinical potential in the treatment of acute myocardial infarction. We hypothesize that postischemic administration of 17beta-estradiol will decrease myocardial ischemia/reperfusion injury and improve left ventricular cardiac function.. Adult male Sprague Dawley rat hearts (n = 20) (Harlan, Indianapolis, IN) were isolated, perfused with Krebs-Henseleit solution via Langendorff model, and subjected to 15 min of equilibration, 25 min of warm ischemia, and 40 min reperfusion. Experimental hearts received postischemic 17beta-estradiol infusion, 1 nm (n = 4), 10 nm (n = 4), 25 nm (n = 4), or 50 nm (n = 4), throughout reperfusion. Control hearts (n = 4) were infused with perfusate vehicle.. Postischemic recovery of left ventricular developed pressure was significantly greater with 1 nm (51.6% +/- 7.4%) and 10 nm estradiol (47.7% +/- 8.6%) than with vehicle (37.8% +/- 9.7%) at end reperfusion. There was also greater recovery of the end diastolic pressure with 1 nm (47.8 +/- 4.0 mmHg) and 10 nm estradiol (54.0 +/- 4.0) compared with vehicle (75.3 +/- 7.5). Further, 1 nm and 10 nm estrogen preserved coronary flow after ischemia and decreased coronary effluent lactated dehydrogenase compared with controls. Estrogen at 25 nm and 50 nm did not provide additional benefit in terms of functional recovery. Estrogen at all concentrations increased extracellular signal-regulated protein kinase phosphorylation.. Postischemic infusion of 17beta-estradiol protects myocardial function and viability. The attractive potential for the clinical application of postischemic estrogen therapy warrants further study to elucidate the mechanistic pathways and differences between males and females.

Topics: Animals; Cardiovascular Agents; Estradiol; Heart; Male; Myocardial Ischemia; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Tissue Survival; Ventricular Function, Left

Ischemic and non-ischemic cardiomyopathy (ICM and NICM) both cause heart failure, but the different etiologies may result in differences in management and outcome, which were explored in this study.. Cohort study of 168 consecutive patients (90 ICM, 78 NICM) recruited from a tertiary referral heart failure clinic followed for 40+/-19 months.. Patients with ICM were older than NICM with worse NYHA functional state but similar left ventricular ejection fraction (LVEF) and dimensions at baseline. Similar proportions (>80%) in both groups were on a beta-blocker and angiotensin-converting-enzyme inhibitor and/or angiotensin-II-receptor blocker (ACE inhibitor+/-ARB) by end of study. Mean LVEF improved in both groups over time (27.3+/-11.9% vs. 33.1+/-12.6%, p<0.05). Overall 40-month mortality was 17%. In univariate analysis of patients <80 years old, ICM, NYHA class, serum creatinine, ACE inhibitor+/-ARB, and amiodarone use were predictors of mortality, but only serum creatinine was significant in multivariate analysis, with a 2.9-fold relative risk of death (95%CI, 1.34-6.42, p<0.01) for creatinine >/=120 micromol/L compared to <120 micromol/L.. Mortality of patients with cardiomyopathy remains high and is strongly related to serum creatinine. NICM patients were younger and showed greater improvement in symptoms and left ventricular function in long-term follow-up.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathy, Dilated; Cardiovascular Agents; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Pilot Projects; Prognosis; Prospective Studies; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke Volume; Treatment Outcome; Ventricular Function, Left

We determined the prescription rates of medications for the secondary prevention of ischaemic heart disease and left ventricular systolic dysfunction in stable dialysis patients. In patients with established ischaemic heart disease, statins, beta-blockers and renin-angiotensin-aldosterone system blockers were substantially underprescribed. Furthermore, beta-blockers and renin-angiotensin-aldosterone system blockers were prescribed in less than half of those with left ventricular systolic dysfunction. Contraindications to treatment were infrequent and did not explain these findings.

Topics: Cardiovascular Agents; Heart Failure; Humans; Myocardial Ischemia; Renal Dialysis

A 67-year-old man was admitted to a coronary care unit for non-ST-segment elevation myocardial infarction with complicating acute heart failure. Severe mitral regurgitation was detected by echocardiography at presentation. Repeat echocardiography carried out during another ischemic episode revealed a marked reduction in the patient's mitral regurgitation that was related to decreased apical traction of the valve leaflets.. Physical examination, electrocardiography, laboratory tests, coronary angiography, chest radiography, echocardiography.. Mitral regurgitation associated with acute coronary syndrome.. Early revascularization by percutaneous coronary intervention, supported by pharmacological therapy to decrease left ventricular filling pressure.

Topics: Acute Disease; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Echocardiography, Doppler, Color; Humans; Male; Mitral Valve; Mitral Valve Insufficiency; Myocardial Contraction; Myocardial Ischemia; Papillary Muscles; Ventricular Function, Left

Hydroxymethyl glutaryl (HMG)-coenzyme A (CoA) reductase inhibitors (statins) protect the myocardium against ischemia-reperfusion injury via a mechanism unrelated to cholesterol lowering. Statins may inhibit isoprenylation and thereby prevent activation of proteins such as RhoA. We hypothesized that statins protect the myocardium against ischemia-reperfusion injury via a mechanism involving inhibition of geranylgeranyl pyrophosphate synthesis and translocation of RhoA to the plasma membrane. Sprague-Dawley rats were given either the HMG-CoA reductase inhibitor rosuvastatin, geranylgeranyl pyrophosphate dissolved in methanol, the combination of rosuvastatin and geranylgeranyl pyrophosphate, rosuvastatin and methanol, or distilled water (control) by intraperitoneal injection for 48 h before ischemia-reperfusion. Animals were anesthetized and either subjected to 30 min of coronary artery occlusion followed by 2 h of reperfusion where at infarct size was determined, or the expression of RhoA protein was determined in cytosolic and membrane fractions of nonischemic myocardium. There were no significant differences in hemodynamics between the control group and the other groups before ischemia or during ischemia and reperfusion. The infarct size was 80 +/- 3% of the area at risk in the control group. Rosuvastatin reduced infarct size to 64 +/- 2% (P<0.001 vs. control). Addition of geranylgeranyl pyrophosphate (77 +/- 2%, P<0.01 vs. rosuvastatin) but not methanol (65 +/- 2%, not significant vs. rosuvastatin) abolished the cardioprotective effect of rosuvastatin. Geranylgeranyl pyrophosphate alone did not affect infarct size per se (84 +/- 2%). Rosuvastatin increased the cytosol-to-membrane ratio of RhoA protein in the myocardium (P<0.05 vs. control). These changes were abolished by addition of geranylgeranyl pyrophosphate. We conclude that the cardioprotection and the increase of the RhoA cytosol-to-membrane ratio induced by rosuvastatin in vivo are blocked by geranylgeranyl pyrophosphate. The inhibition of geranylgeranyl pyrophosphate formation and subsequent modulation of cytosol/membrane-bound RhoA are of importance for the protective effect of statins against myocardial ischemia-reperfusion injury.

Topics: Animals; Cardiovascular Agents; Cell Membrane; Cytosol; Disease Models, Animal; Fluorobenzenes; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Polyisoprenyl Phosphates; Protein Transport; Pyrimidines; Rats; Rats, Sprague-Dawley; rhoA GTP-Binding Protein; Rosuvastatin Calcium; Sulfonamides

This study investigated the effects of increasing doses of rac-perhexiline maleate and CYP2D6 phenotype and genotype on the pharmacokinetics of (+) and (-)-perhexiline.. In a prospective study, steady-state plasma concentrations of (+) and (-)-perhexiline were quantified in 10 CYP2D6 genotyped patients following dosing with 100 mg/day rac-perhexiline maleate, and following a subsequent dosage increase to 150 or 200 mg/day. In a retrospective study, steady-state plasma concentrations of (+) and (-)-perhexiline were obtained from 111 CYP2D6 phenotyped patients receiving rac-perhexiline maleate.. In the prospective study, comprising one poor and nine extensive/intermediate metabolizers, the apparent oral clearance (CL/F) of both enantiomers increased with the number of functional CYP2D6 genes. In the nine extensive/intermediate metabolizers receiving the 100 mg/day dose, the median CL/F of (+)-perhexiline was lower than that of (-)-perhexiline (352.5 versus 440.6 l/day, P<0.01). Following the dosage increase, the median CL/F of both enantiomers decreased by 45.4 and 41.4%, respectively. In the retrospective study, the median (+)-/(-)-perhexiline plasma concentration ratio was lower (P<0.0001) in phenotypic extensive/intermediate (1.41) versus poor metabolizers (2.29). Median CL/F of (+) and (-)-perhexiline was 10.6 and 24.2 l/day (P<0.05), respectively, in poor metabolizers, and 184.1 and 272.0 l/day (P<0.001), respectively, in extensive/intermediate metabolizers.. Perhexiline's pharmacokinetics exhibit significant enantioselectivity in CYP2D6 extensive/intermediate and poor metabolizers, with both enantiomers displaying polymorphic and saturable metabolism via CYP2D6. Clinical use of rac-perhexiline may be improved by developing specific enantiomer target plasma concentration ranges.

Topics: Biological Availability; Cardiovascular Agents; Cytochrome P-450 CYP2D6; Genotype; Humans; Metabolic Clearance Rate; Myocardial Ischemia; Perhexiline; Phenotype; Polymorphism, Genetic; Prospective Studies; Retrospective Studies; Sensitivity and Specificity; Stereoisomerism

Maternal heart disease during pregnancy is the main cause of obstetric morbidity and mortality. We report the case of a 40-year-old woman with a history of myocardial infarction and percutaneous transluminal coronary angioplasty. The patient suffered a second heart attack and received pharmacologic treatment. After admission, she was seen to be 29 weeks pregnant. Delivery was by cesarean section under progressive epidural block without complications. We review the medical, obstetric, and anesthetic implications of myocardial infarction during pregnancy. The management of such patients should be multidisciplinary and decisions about delivery should be taken based on obstetric considerations.

Topics: Adult; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cesarean Section; Combined Modality Therapy; Contraindications; Coronary Angiography; Diagnosis, Differential; Elective Surgical Procedures; Ergotamine; Female; Humans; Myocardial Infarction; Myocardial Ischemia; Obesity, Morbid; Oxytocin; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy, High-Risk; Recurrence; Stents; Thrombophilia

Microvascular dysfunction in hypertrophic cardiomyopathy (HCM) may create an ischemic substrate conducive to sudden death, but it remains unknown whether the extent of hypertrophy is associated with proportionally poorer perfusion reserve. Comparisons between magnitude of hypertrophy, impairment of perfusion reserve, and extent of fibrosis may offer new insights for future clinical risk stratification in HCM but require multiparametric imaging with high spatial and temporal resolution.. Degree of hypertrophy, myocardial blood flow at rest and during hyperemia (hMBF), and myocardial fibrosis were assessed with magnetic resonance imaging in 35 HCM patients (9 [26%] male/26 female) and 14 healthy controls (4 [29%] male/10 female), aged 18 to 78 years (mean+/-SD, 42+/-14 years) with the use of the American Heart Association left ventricular 16-segment model. Resting MBF was similar in HCM patients and controls. hMBF was lower in HCM patients (1.84+/-0.89 mL/min per gram) than in healthy controls (3.42+/-1.76 mL/min per gram, with a difference of -0.95+/-0.30 [SE] mL/min per gram; P<0.001) after adjustment for multiple variables, including end-diastolic segmental wall thickness (P<0.001). In HCM patients, hMBF decreased with increasing end-diastolic wall thickness (P<0.005) and preferentially in the endocardial layer. The frequency of endocardial hMBF falling below epicardial hMBF rose with wall thickness (P=0.045), as did the incidence of fibrosis (P<0.001).. In HCM the vasodilator response is reduced, particularly in the endocardium, and in proportion to the magnitude of hypertrophy. Microvascular dysfunction and subsequent ischemia may be important components of the risk attributable to HCM.

Topics: Adolescent; Adult; Aged; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Contrast Media; Coronary Circulation; Endocardium; Female; Fibrosis; Gadolinium DTPA; Humans; Hyperemia; Image Processing, Computer-Assisted; Magnetic Resonance Angiography; Male; Microcirculation; Middle Aged; Myocardial Ischemia; Myocardium; Rest; Risk; Vasodilation

Sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) both significantly reduce the need for repeat intervention compared to bare metal stents. Studies comparing the clinical outcomes of these stents in noncomplex subsets of patients and lesions demonstrate a similar safety and efficacy profile. The data for more complex subsets of patients and lesions remains conflicting. This study aimed to compare SES with PES in a selected population with a broad range of complex features.. The patient population consisted of 1,591 consecutive patients with complex features undergoing drug-eluting stent (DES) implantation. In the SES group there were 1,095 patients (1,653 lesions) and in the PES group 496 patients (802 lesions). In-hospital, 30-day, and 12-month clinical outcomes were compared between groups. No discernable difference in major adverse cardiac events (MACE) between SES and PES was detected at intermediate and longer-term follow-up (SES 22.4% vs. PES 20.5% at 12 months; P=0.407). A trend toward increased angiographically documented stent thrombosis was observed in the SES group at both 3 and 12 months (SES 2.2% vs. PES 0.8% at 12 months; P=0.051). When adopting the more inclusive definition of probable stent thrombosis, this trend was no longer seen. After adjusting for baseline differences between the two groups, there still remained no difference in MACE between SES and PES (HR 1.051 [CI 0.826-1.339] P=0.685). The trend toward increased angiographically documented stent thrombosis in the SES group remained after adjustment for baseline differences (HR 2.836 [CI 0.968-8.311] P=0.057).. In a selected population with complex disease the rate of MACE was comparable between SES and PES, with higher overall rates of thrombosis and MACE compared to a noncomplex population. Thus, the focus should be directed to prevent late complications in this complex subset regardless of stent type selection.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cardiovascular Diseases; Coronary Angiography; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Paclitaxel; Proportional Hazards Models; Prosthesis Design; Research Design; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sirolimus; Stents; Thrombosis; Time Factors; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Cardiomyopathies; Cardiovascular Agents; Cardiovascular Diseases; Coronary Artery Bypass; Humans; Myocardial Ischemia; Paclitaxel; Patient Selection; Prosthesis Design; Radiography; Severity of Illness Index; Sirolimus; Stents; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left

The purpose of this study was to determine whether hemodynamic and pharmacologic factors can influence the extent and severity of myocardial necrosis produced by coronary occlusion. In 48 dogs, 10 to 14 epicardial leads were recorded on the anterior surface of the left ventricle in the distribution and vicinity of the site of occlusion of a branch of the left anterior descending coronary artery. The average S-T segment elevation for each animal was determined at 5-min intervals after occlusion. This elevation was used as an index of the presence and severity of myocardial ischemic injury. Isoproterenol, ouabain, glucagon, bretylium, and tachycardia given prior to a repeated occlusion each increased the severity and extent of ischemic injury, while propranolol decreased it. Elevation of arterial pressure with methoxamine reduced the occlusion-induced S-T segment elevation, and lowering of the mean arterial pressure by hemorrhage had the opposite effect. In 19 additional experiments, propranolol, isoproterenol, and alterations in arterial pressure produced similar alterations in S-T segment elevation when these interventions were applied as long as 3 hr after ligation. Myocardial creatine phosphokinase (CPK) activity determined 24 hr after coronary artery ligation correlated well with S-T segment elevation at the same sites recorded 15 min after ligation. Moreover, isoproterenol increased and propranolol decreased the area of depression of myocardial CPK activity. We conclude that the hemodynamic status and neurohumoral background at the time of coronary occlusion and for at least 3 hr thereafter can alter the extent and severity of myocardial ischemic injury and myocardial necrosis.

Topics: Anesthesiology; Animals; Atorvastatin; Blood Pressure; Cardiovascular Agents; Coronary Disease; Dogs; Heart Diseases; Heart Rate; Heptanoic Acids; History, 20th Century; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Ischemia; Myocardial Revascularization; Necrosis; Oxygen; Pyrroles

We compared the outcome of drug eluting stent (DES) implantation (Sirolimus or Paclitaxel) in patients with ischemic cardiomyopathy and severe left ventricular (LV) dysfunction with the outcome of a similar group of patients undergoing coronary artery by-pass grafting (CABG).. Revascularization provides long-term benefits in patients with severe LV dysfunction. However the modality to achieve it is still unsettled in this high risk group of patients.. Two-hundred-twenty patients (20% women) with severe LV dysfunction (LV Ejection Fraction

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiomyopathies; Cardiovascular Agents; Cardiovascular Diseases; Coronary Angiography; Coronary Artery Bypass; Female; Follow-Up Studies; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Ischemia; Paclitaxel; Prosthesis Design; Research Design; Retrospective Studies; Severity of Illness Index; Sirolimus; Stents; Time Factors; Treatment Outcome; United States; Ventricular Dysfunction, Left

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Biomarkers; Cardiology; Cardiovascular Agents; Heart Failure; Heart Transplantation; History, 20th Century; History, 21st Century; Humans; Hungary; Myocardial Infarction; Myocardial Ischemia; Severity of Illness Index; Thrombolytic Therapy

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cardiovascular Diseases; Humans; Myocardial Ischemia; Paclitaxel; Patient Selection; Prosthesis Design; Risk Assessment; Severity of Illness Index; Sirolimus; Stents; Thrombosis; Treatment Outcome

The performance of drug eluting stents (DES) and impact on every day practice in the USA, where complex, nonselective cases are the rule, remain unknown.. The Brigham and Women's Hospital interventional experience in the bare metal stents (BMS) (6/2002 to 2/2003) and after abrupt and near universal adoption of DES (4/2003 to 9/2004) were compared. Demographic, procedural and in-hospital outcomes for all consecutive cases where investigated. Predictors and angiographic characteristics of patients returning for clinically driven target lesion revascularization (TLR) in both eras were analyzed.. Of 2,555 DES cases (3,061 lesions, 87.9% Cypher, 12.1% Taxus), 47 underwent TLR during follow-up (68 lesions, 2.2%). Of the 1,731 BMS cases (1,798 lesions), 162 underwent clinically indicated TLR (209 lesions, 11.6%), representing an 81% DES era TLR risk reduction. Multivariate predictors of TLR in the DES era: left main lesion (LM) (odds ratio (OR) 7.65, 95% confidence interval (CI) 3.33-17.53, P<0.01, treatment of restenosis (OR 5.96, CI 3.21-11.08, P<0.01), and diabetes (OR 1.68, CI 0.92-3.04, P=0.07). Predictors of restenosis in the BMS era included additional clinical, lesion, and stent characteristics, while LM lesion was absent. Angiographic patterns of stent restenosis differed in the DES (focal) and BMS (diffuse) era.. The transition from BMS to DES in the setting of a large USA hospital practice is safe and associated with significant reduction in clinically driven TLR. Treatment of specific lesions types (repeat restenosis, distal LM) and diabetic patients remain suboptimal and warrant further investigation.

Topics: Aged; Angioplasty, Balloon, Coronary; Boston; Cardiovascular Agents; Cardiovascular Diseases; Coronary Angiography; Coronary Restenosis; Diabetes Complications; Female; Follow-Up Studies; Humans; Incidence; Logistic Models; Male; Metals; Middle Aged; Myocardial Ischemia; Odds Ratio; Prospective Studies; Prosthesis Design; Registries; Research Design; Risk Assessment; Risk Factors; Stents; Time Factors; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Cardiovascular Diseases; Coronary Restenosis; Diabetes Complications; Humans; Incidence; Metals; Myocardial Ischemia; Prosthesis Design; Risk Assessment; Risk Factors; Stents; Treatment Outcome

Drug-eluting stents (DES) present a slightly higher incidence of stent thrombosis compared to bare metal stents and some cases of DES thrombosis are described in the literature. Therefore, there is consensus in recommending treatment with clopidogrel for at least 6 months in addition to life-long aspirin administration. We describe a case of very late paclitaxel-eluting stent thrombosis despite 21 months of clopidogrel treatment, which occurred just 2 weeks after its withdrawal, causing an acute coronary syndrome that was promptly resolved with an urgent invasive strategy. In our experience, paclitaxel-eluting stent thrombosis can occur several months after stent implantation despite prolonged clopidogrel treatment.

Topics: Acute Disease; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Clopidogrel; Coronary Angiography; Coronary Thrombosis; Humans; Male; Middle Aged; Myocardial Ischemia; Paclitaxel; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Prosthesis Design; Stents; Syndrome; Ticlopidine; Time Factors; Treatment Outcome

The aim of this study was to investigate the impact of statin on systemic inflammation, left ventricular systolic and diastolic function and prognosis in low risk ischemic heart disease (IHD) patients.. A total of 430 consecutive IHD patients without congestive heart failure were enrolled. One hundred and thirty-two patients (31%) were treated with statin (statin group) and 298 patients (69%) were not (no statin group). Echocardiographic indices, high sensitivity CRP, and prognosis were compared.. Ejection fraction (EF) was significantly higher in the statin group (p<0.01). The ratio of the early transmitral flow velocity to early diastolic velocity of the mitral annulus (E/E') was significantly lower in the statin group than in the no statin group (p<0.01). Although LDL-cholesterol level did not differ, high sensitivity CRP level was significantly lower in the statin group (0.3+/-0.5 vs. 1.1+/-2.3 mg/dl, p=0.005). Cardiac event-(cardiac death and congestive heart failure)free survival rate was significantly higher in the statin group than in no statin group (Log-rank p<0.0001). By multivariate logistic regression analysis, E/E' > 15 (p=0.002), EF < 50% (p=0.003), lack of statin use (p=0.009), left atrial dimension (p=0.02), use of diuretics (p=0.03) and lack of beta-blockers (p=0.04) were independent predictors of cardiac events. In 248 patients matched by propensity scores, statin remained associated with better event-free survival (Log-rank p=0.006).. Statin may improve left ventricular function and thus improve the prognosis in low risk patients with IHD.

Topics: Aged; Cardiovascular Agents; Diastole; Female; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Myocardial Ischemia; Prognosis; Systole; Ventricular Function, Left

To analyse the kinetic changes of uptake, washout and retention of Tc-sestamibi in order to evaluate the protective effects and possible mechanism of ischaemic preconditioning and adenosine preconditioning on myocardium injured by ischaemia/reperfusion.. Isolated ischaemia/reperfusion rabbit heart models, as established by Langendorff, were used. Eighteen rabbit hearts perfused in Krebs-Henseleit (KH) buffer were randomly assigned to three groups: ischaemia/reperfusion (I/R, n=6), adenosine preconditioning (AD, n=6), and ischaemic preconditioning (IPC, n=6). Tc-sestamibi (55.5 MBq) in KH was perfused for 40 min and washed out for 40 min. The kinetic changes of Tc-sestamibi within myocardial tissue was monitored during the uptake and washout phases. Cardiac haemodynamic parameters, creatine kinase and lactate dehydrogenase leakage in coronary effluent, and myocardial infarct size were measured to assess myocardial injuries in rabbit hearts.. In the early phases of uptake, there were no significantly different uptake rates of Tc-sestamibi between AD (before 20 min), IPC (before 15 min) and I/R myocardium (all P>0.05). Uptake rates of Tc-sestamibi in myocardium of the three groups all tended to increase, with the uptake time increasing. In the late phases of uptake, AD and IPC were significantly higher than I/R (all P<0.05). In the washout phases, the retention fractions of Tc-sestamibi in myocardium of the three groups all showed a descending tendency with washout time increasing. The retention fractions in AD and IPC were all higher than I/R (all P<0.05). There were no statistical differences in uptake rates and retention fractions of Tc-sestamibi between AD and IPC (all P>0.05). Cardiac haemodynamic parameters, creatine kinase and lactate dehydrogenase leakage, and myocardial infarct size demonstrated there is lighter injury in AD and IPC myocardium than in I/R (all P<0.05). The retention of Tc-sestamibi and myocardial infarction weight were significantly negatively correlated (r=-0.8384, P<0.001).. Adenosine preconditioning has similar myocardial protective effects on ischaemia/reperfusion myocardium as does ischaemic preconditioning. Tc-sestamibi may be a sensitive and reliable measure for evaluating the importance and mechanism of ischaemic preconditioning and adenosine preconditioning.

Topics: Adenosine; Animals; Blood Pressure; Cardiovascular Agents; Heart; Heart Rate; In Vitro Techniques; Ischemic Preconditioning, Myocardial; Male; Myocardial Infarction; Myocardial Ischemia; Myocardium; Positron-Emission Tomography; Rabbits; Radiopharmaceuticals; Reperfusion Injury; Technetium Tc 99m Sestamibi

Cardiomyocyte energy production during ischemia depends upon anaerobic glycolysis inefficiently yielding two ATP per glucose. Substrate augmentation with fructose 1,6-diphosphate (FDP) bypasses the ATP consuming steps of glucokinase and phosphofructokinase thus yielding four ATP per FDP. This study evaluated the impact of FDP administration on myocardial function after acute ischemia.. Male Wistar rats, 250-300 g, underwent 30 min occlusion of the left anterior descending coronary artery followed by 30 min reperfusion. Immediately prior to both ischemia and reperfusion, animals received an intravenous bolus of FDP or saline control. After 30 min reperfusion, myocardial function was evaluated with a left ventricular intracavitary pressure/volume conductance microcatheter. For bioenergetics studies, myocardium was isolated at 5 min of ischemia and assayed for ATP levels.. Compared to controls (n=8), FDP animals (n=8) demonstrated significantly improved maximal left ventricular pressure (100.5+/-5.4 mmHg versus 69.1+/-1.9 mmHg; p<0.0005), dP/dt (5296+/-531 mmHg/s versus 2940+/-175 mmHg/s; p<0.0028), ejection fraction (29.1+/-1.7% versus 20.4+/-1.4%; p<0.0017), and preload adjusted maximal power (59.3+/-5.0 mW/microL(2) versus 44.4+/-4.6 mW/microL(2); p<0.0477). Additionally, significantly enhanced ATP levels were observed in FDP animals (n=5) compared to controls (n=5) (535+/-156 nmol/g ischemic tissue versus 160+/-9.0 nmol/g ischemic tissue; p<0.0369).. The administration of the glycolytic intermediate, FDP, by intravenous injection, resulted in significantly improved myocardial function after ischemia and improved bioenergetics during ischemia.

Topics: Adenosine Triphosphate; Animals; Anti-Arrhythmia Agents; Cardiovascular Agents; Fructosediphosphates; Glycolysis; Injections, Intravenous; Male; Models, Animal; Myocardial Ischemia; Myocardial Reperfusion Injury; Phosphofructokinase-1; Rats; Rats, Wistar; Ventricular Dysfunction, Left

Topics: Acetylcholine; Angina Pectoris; Bundle-Branch Block; Calcium Channel Blockers; Cardiovascular Agents; Coronary Vasospasm; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Humans; Myocardial Ischemia; Syncope; Ventricular Fibrillation

Two patients with life-threatening episodes of ventricular fibrillation (VF) showed typical ST elevation in V1-V3 leads. Both had spontaneous clinical episodes of resting angina. Intracoronary injection of acetylcholine provoked coronary vasospasm and ST elevation was the same as Brugada-type ST elevation in 1 case but not in the other. Calcium channel antagonist was prescribed to prevent coronary vasospasm but Brugada-type ST elevation and the occurrence of VF could not be prevented. The symptoms accompanied both cases. Considering these cases, the pathogenesis of Brugada syndrome should differ from that of coronary vasospasm because it could not be prevented by calcium channel antagonist.

Topics: Acetylcholine; Amlodipine; Calcium Channel Blockers; Cardiovascular Agents; Coronary Vasospasm; Defibrillators, Implantable; Diltiazem; Electric Countershock; Electrocardiography; Fatal Outcome; Heart Function Tests; Humans; Male; Middle Aged; Myocardial Ischemia; Syncope; Ventricular Fibrillation

CYP2D6 protein expression is determined by the number of functional CYP2D6 alleles. It is also higher in individuals with at least one CYP2D6*2 allele. This study has investigated the effect of the number of functional CYP2D6 alleles and the influence of CYP2D6*2 alleles on plasma perhexiline concentrations in patients administered a standard loading regimen over 3 days.. Eighteen patients with myocardial ischaemia who were not taking any drugs known to inhibit CYP2D6 metabolism in vivo commenced treatment with 200 mg of perhexiline twice per day. On the fourth day, blood was drawn for genotyping and the measurement of trough plasma concentrations of perhexiline and its major metabolite, cis-OH-perhexiline.. The only genotypic CYP2D6 poor metabolizer had a trough plasma perhexiline concentration of 2.70 mg l-1 and no detectable cis-OH-perhexiline. The mean+/-SD trough plasma perhexiline concentration in patients with one functional allele was significantly higher (0.63+/-0.31 mg l-1, n=8, P=0.05) than in patients with two functional alleles (0.37+/-0.17 mg l-1, n=9). Conversely, the mean metabolic ratio was significantly lower in patients with one functional allele (2.90+/-1.76, P<0.01) compared with patients with two functional alleles (6.52+/-3.26). Patients with at least one CYP2D6*2 allele had a lower plasma perhexiline concentration (0.20+/-0.09 mg l-1, n=5, P<0.001) and a higher metabolic ratio (7.86+/-2.51, P<0.01) than the non-poor metabolizer patients with no CYP2D6*2 alleles (0.62+/-0.23 mg l-1 and 3.55+/-2.54, respectively, n=12).. Patients with only one functional allele and not CYP2D6*2 have diminished CYP2D6 metabolic capacity for perhexiline.

Topics: Aged; Aged, 80 and over; Alleles; Cardiovascular Agents; Cytochrome P-450 CYP2D6; Gene Frequency; Genotype; Humans; Middle Aged; Myocardial Ischemia; Perhexiline; Polymorphism, Single Nucleotide

Topics: Cardiovascular Agents; Gastrointestinal Diseases; Humans; Myocardial Ischemia; Treatment Outcome

Ivabradine is the first selective and specific inhibitor of the I(f) current (the cardiac pacemaker 'funny' current), and provides pure heart rate reduction without altering myocardial contractility, the cardiac conduction system or coronary vascular resistance. Clinical proof of the antianginal efficacy and tolerability of ivabradine comes from the largest clinical development programme that has ever been performed in stable angina, involving more than 5000 patients. Ivabradine was shown to be as effective as well-established reference antianginal drugs, such as beta-blockers and calcium antagonists. It is well tolerated and is free of the most commonly observed side effects of currently prescribed antianginal drugs. It offers clear therapeutic benefits for a whole range of patients with stable angina, including those with contraindications or intolerance to beta-blockers.

Topics: Adrenergic beta-Antagonists; Angina Pectoris; Animals; Benzazepines; Calcium Channel Blockers; Cardiovascular Agents; Drug Administration Schedule; Drug Evaluation, Preclinical; Drug Therapy, Combination; Heart Rate; Humans; Ivabradine; Myocardial Ischemia; Nitrates; Randomized Controlled Trials as Topic; Sinoatrial Node

We examined the efficacy of drug-eluting stent (DES) implantation (Sirolimus or Paclitaxel) in patients with ischemic cardiomyopathy and severe left ventricular (LV) dysfunction and compared the outcome with a similar group of patients undergoing bare metal stent (BMS) implantation.. Patients with severe LV dysfunction are a high risk group. DES may improve the long term outcomes compared with BMS.. One hundred and ninety one patients (23% women) with severe LV dysfunction (LV ejection fraction < or =35%) underwent coronary stent implantation between May 2002 and May 2005 and were available for follow-up. One hundred and twenty eight patients received DES (Sirolimus in 72 and Paclitaxel in 54) and 63 patients had BMS. Patients with acute S-T elevation myocardial infarction (STEMI) were excluded. The primary endpoint was cardiovascular mortality. A composite endpoint of major adverse cardiac events (MACE) including cardiovascular mortality, myocardial infarction (MI), and target vessel revascularization (TVR) was the secondary endpoint.. Mean follow-up was 420 +/- 271 days. No differences were noted in age (69 +/- 10 years vs. 70 +/- 10 years, P = NS), number of vessel disease (2.3 +/- 0.7 vs. 2.2 +/- 0.8, P = NS), history of congestive heart failure (47% vs. 46%, P = NS), MI (60% vs. 61%, P = NS), or number of treated vessels (1.3 +/- 0.5 vs. 1.3 +/- 0.6, P = NS) for the DES and BMS group, respectively. Diabetes was more common among DES patients (45% vs. 25%, P = 0.01). The left ventricular ejection fraction (LVEF) was similar between the two groups (28% +/- 6% vs. 26% +/- 8%, P = NS for the DES and BMS, respectively). During the follow-up, there were a total of 25 deaths of which two were cancer related (2 in DES group). There were 23 cardiac deaths, 8/126 (6%) which occurred in the DES group and 15/63 (24%) in the BMS group (P = 0.05 by log-rank test). MACE rate was 10% for the DES group and 41% for the BMS group (P = 0.003). NYHA class improved in both groups (from 2.5 +/- 0.8 to 1.7 +/- 0.8 in DES and from 2 +/- 0.8 to 1.4 +/- 0.7 in the BMS, P = NS).. Compared with bare-metal stents, DES implantation reduces mortality and MACE in high risk patients with severe left ventricular dysfunction.

Topics: Aged; Aged, 80 and over; Blood Vessel Prosthesis Implantation; Cardiomyopathies; Cardiovascular Agents; Coated Materials, Biocompatible; Coronary Angiography; Female; Follow-Up Studies; Heart Failure; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Paclitaxel; Prosthesis Design; Research Design; Severity of Illness Index; Sirolimus; Stents; Stroke Volume; Survival Rate; Treatment Outcome; United States; Ventricular Dysfunction, Left

Secondary prevention is needed following coronary artery bypass graft (CABG) surgery to reduce the subsequent risk of unstable angina, myocardial infarction and death. However, little research exists on the use of cardiovascular medical therapy in CABG surgery patients. The objective of the present study is to describe the use of cardiovascular medical therapy among patients discharged after CABG surgery.. The use of acetylsalicylic acid, clopidogrel, warfarin, antilipid agents, beta-blockers, calcium channel blockers, nitrates and angiotensin-converting enzyme (ACE) inhibitors was examined among 320 patients enrolled in the Routine versus Selective Exercise Treadmill Testing After Coronary Artery Bypass Graft Surgery (ROSETTA-CABG) Registry. Logistic regression identified the determinants of medication use at 12 months following CABG surgery.. Most patients were male, hyperlipidemic and underwent CABG surgery for relief of angina symptoms. At admission, discharge and at 12 months, acetylsalicylic acid was used in 71%, 92% and 87% of cases, respectively, and some form of antiplatelet agent was used in 74%, 94% and 89% of cases, respectively. The use of antilipid agents remained constant, from 55% at admission to 57% at discharge. However, 24% of patients were not receiving antilipid agents at 12 months. The use of beta-blockers was 57% at admission, 71% at discharge and 64% at 12 months. The use of calcium channel blockers and nitrates decreased modestly from admission to discharge and remained stable at approximately 20% and 22%, respectively, at 12 months. ACE inhibitor use remained stable, from 33% at admission to 38% at 12-months. Hyperlipidemia, hypertension, obesity and pre-CABG surgery left ventricular ejection fraction less than 40% were all found to be important determinants of 12-month medication use. Importantly, the use at discharge was an important determinant of 12-month use of for each medication examined in the present study.. The use of antilipid agents, beta-blockers and ACE inhibitors was found to be too low among post-CABG surgery patients, who are known to benefit from their use, and the use of nitrates was too high. Discharge from hospital provides a unique opportunity for physicians to modify the use of cardiovascular medical therapy among patients undergoing CABG surgery.

Topics: Aged; Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Cardiovascular Agents; Coronary Artery Bypass; Coronary Artery Disease; Europe; Exercise Test; Female; Follow-Up Studies; Humans; Hypolipidemic Agents; Male; Middle Aged; Myocardial Ischemia; North America; Pakistan; Platelet Aggregation Inhibitors; Postoperative Complications; Prospective Studies; Registries; Stroke Volume; Treatment Outcome

Topics: Cardiovascular Agents; Clinical Trials as Topic; Epidemiologic Studies; Humans; Myocardial Ischemia; Spain

With the reduction in restenosis rates by drug-eluting stents, there is new controversy concerning the optimal management of incidental, nontarget lesions identified during percutaneous coronary intervention (PCI). Such lesions have been treated conservatively because of risk of restenosis but now are being considered for PCI to prevent plaque instability. However, the impact of incidental stenoses on future cardiac events remains unknown.. We performed a retrospective cohort study to determine the rate and features of clinical plaque progression using the National Heart, Lung, and Blood Institute Dynamic Registry of consecutive patients undergoing PCI at multiple centers in 1997 to 1998 and 1999. Of 3747 PCI patients, 216 (5.8%) required additional nontarget lesion PCI for clinical plaque progression at 1 year. Fifty-nine percent presented with new unstable angina, and 9.3% presented with nonfatal myocardial infarction. Patients with multivessel coronary artery disease during original PCI were more likely to require nontarget lesion PCI during follow-up (adjusted odds ratio, 1.72 [95% CI, 1.18 to 2.52] for 2 vessels; adjusted odds ratio, 3.37 [95% CI, 2.32 to 4.89] for 3 vessels). Angiographic review showed that the majority (86.9%) of lesions requiring subsequent PCI were < or =60% in severity during original PCI, with the mean lesion stenosis 41.8+/-20.8% at the time of the initial PCI and 83.9+/-13.9% during the recurrent event.. Approximately 6% of PCI patients will have clinical plaque progression requiring nontarget lesion PCI by 1 year. Greater coronary artery disease burden confers a significantly higher risk for clinical plaque progression.

Topics: Angioplasty, Balloon, Coronary; Cardiac Catheterization; Cardiovascular Agents; Cohort Studies; Combined Modality Therapy; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Disease Progression; Follow-Up Studies; Humans; Incidental Findings; Life Tables; Myocardial Infarction; Myocardial Ischemia; Registries; Retrospective Studies; Risk; Stents

In order to assess adherence to guidelines and international variability in management, the Euro Heart Survey of Newly Presenting Angina prospectively studied medical therapy, percutaneous coronary intervention (PCI), and surgery in patients with new-onset stable angina in Europe.. Consecutive patients, 3779 in total, with a clinical diagnosis of stable angina by a cardiologist were enrolled. After initial assessment by a cardiologist, 78% were treated with aspirin, 48% with a statin, and 67% with a beta-blocker. ACE-inhibitors were prescribed by the cardiologist in 37% overall. Revascularization rates were low, with only 501 (13%) patients having PCI or coronary bypass surgery performed or planned. However, when restricted to patients with coronary disease documented within 4 weeks of assessment, over 50% had revascularization performed or planned. Among other factors, the national rate of angiography and availability of invasive facilities significantly predicted the likelihood of revascularization, OR 2.4 and 2.0, respectively.. This survey shows a shortfall between guidelines and practice with regard to the use of evidence-based drug therapy and evidence that revascularization rates are strongly influenced by non-clinical, in addition to clinical, factors.

Topics: Analysis of Variance; Angina Pectoris; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Decision Making; Europe; Female; Guideline Adherence; Hospitalization; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Revascularization; Practice Guidelines as Topic; Prospective Studies; Referral and Consultation; Regression Analysis

To evaluate the utility of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels to detect myocardial ischemia.. We conducted a prospective observational study in 260 consecutive patients with suspected myocardial ischemia referred for rest/ergometry myocardial perfusion single-photon emission computed tomography. Levels of NT-proBNP were determined before and immediately after symptom-limited bicycle ergometry.. Inducible myocardial ischemia on perfusion images was detected in 129 patients (49.6%). Baseline NT-proBNP and exercise induced increase in NT-proBNP (DeltaNT-proBNP) were significantly higher in patients with myocardial ischemia (median baseline NT-proBNP 155 pg/mL vs 91 pg/mL, P <.001; DeltaNT-proBNP 15 pg/mL vs 7 pg/mL, P = .002). Compared with patients in the lowest DeltaNT-proBNP quartile, those in the highest quartile of DeltaNT-proBNP had three times the risk of inducible ischemia (relative risk, 2.9; 95% confidence interval, 1.4 to 6.0; P = .003). Overall, the accuracy of baseline NT-proBNP and DeltaNT-proBNP in the detection of myocardial ischemia were similar to that of the exercise electrocardiogram (ECG). Combining exercise ECG and baseline NT-proBNP or DeltaNT-proBNP slightly increased the accuracy of exercise ECG only.. The NT-proBNP level at rest as well as DeltaNT-proBNP during exercise stress testing is associated with inducible myocardial ischemia. NT-proBNP levels may have incremental value in the diagnosis of myocardial ischemia.

Topics: Aged; Biomarkers; Cardiovascular Agents; Comorbidity; Electrocardiography; Exercise Test; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Risk Factors; Sensitivity and Specificity; Tomography, Emission-Computed, Single-Photon

Topics: Cardiovascular Agents; Combined Modality Therapy; Humans; Myocardial Ischemia; Treatment Outcome

The CURE study showed that adding clopidogrel to standard therapy with acetylsalicylic acid reduces the risk of cardiovascular events (i.e., stroke, myocardial infarction, and cardiovascular death) in patients with acute coronary syndrome but without ST-segment elevation. The objective of this study was to carry out short- and long-term cost-effectiveness analyses of administering clopidogrel in addition to standard therapy during the first year of treatment.. For the short-term analysis, clinical data and information on health resource utilization were taken from the CURE study. For the long-term analysis, an adaptation of an internationally used Markov model involving six health states was employed. Clinical data were obtained from clinical trials and epidemiological studies. Information on resource use was obtained from two Spanish registries of patients with acute coronary syndrome, a literature review, and consultations with an expert panel. Results are expressed in terms of incremental cost per event avoided or per life-year gained.. In the short-term analysis, the incremental cost per event avoided of adding clopidogrel to standard therapy was ;17 190. In the long-term analysis, the incremental cost per life-year gained was ;8132, which is below the Spanish cost-effectiveness threshold of ;30 000 per life-year gained.. Adding clopidogrel to standard therapy during the first year of treatment is cost-effective in both the short and long term.

Topics: Cardiovascular Agents; Clopidogrel; Cost-Benefit Analysis; Humans; Models, Economic; Myocardial Ischemia; Platelet Aggregation Inhibitors; Spain; Ticlopidine; Treatment Outcome

Ischaemic heart disease and congestive heart failure are common and important conditions in family practice. Effective treatments may be underutilized, particularly in women and the elderly. The objective of the study was to determine the rate of prescribing of evidence-based cardiovascular medications and determine if these differed by patient age or sex.. We conducted a two-year cross-sectional study involving all hospitals in the province of Nova Scotia, Canada. Subjects were all patients admitted with ischaemic heart disease with or without congestive heart failure between 15 October 1997 and 14 October 1999. The main measure was the previous outpatient use of recommended medications. Chi-square analyses followed by multivariate logistic regression analyses were used to examine age-sex differences.. Usage of recommended medications varied from approximately 60% for beta-blockers and angiotensin converting enzyme (ACE) inhibitors to 90% for antihypertensive agents. Patients aged 75 and over were significantly less likely than younger patients to be taking any of the medication classes. Following adjustment for age, there were no significant differences in medication use by sex except among women aged 75 and older who were more likely to be taking beta-blockers than men in the same age group.. The use of evidence-based cardiovascular medications is rising and perhaps approaching reasonable levels for some drug classes. Family physicians should ensure that all eligible patients (prior myocardial infarction, congestive failure) are offered beta-blockers or ACE inhibitors.

Topics: Aged; Ambulatory Care; Cardiology; Cardiovascular Agents; Cross-Sectional Studies; Drug Utilization; Evidence-Based Medicine; Family Practice; Female; Heart Failure; Hospitals, Community; Humans; Male; Middle Aged; Myocardial Ischemia; Nova Scotia

Occlusion of the left main coronary artery for 45 min caused sizable infarct scarring of the left ventricular wall in the rat heart at 14 days post-reperfusion. Daily oral administration of des-aspartate-angiotensin I (DAA-I) for 14 days attenuated the area of the infarct scar and transmurality. The attenuation was dose-dependent and biphasic; maximum effective dose was 1524 nmol/kg, and doses higher than this were progressively inactive. The exact mechanism of the biphasic attenuation is not known, and receptor down-regulation by internalization, which has been implicated in a similar biphasic nature for the anticardiac hypertrophic action of DAA-I, could be a likely cause. Indomethacin (101 micromol/kg, i.p.), administered sequentially after the daily oral dose of DAA-I (1524 nmol/kg), completely inhibited the attenuation at 14 days post-reperfusion, indicating that prostaglandins may be involved in transducing the attenuation. The present findings support earlier indications that DAA-I exerts protective actions in cardiovascular pathologies in which angiotensin II is implicated. It is suggested that DAA-I exerts the cardioprotective action by acting on the same indomethacin-sensitive angiotensin AT1 receptor. Although similar array of protective actions are also seen with another endogenous angiotensin, angiotensin-(1-7), the present findings demonstrate for the first time the ability of an endogenous angiotensin to reduce the infarct size of an ischemic-reperfusion injured rat heart.

Topics: Administration, Oral; Angiotensin I; Animals; Cardiovascular Agents; Indomethacin; Male; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Reperfusion Injury; Prostaglandins; Rats; Rats, Sprague-Dawley

Platelet activation is a hallmark of acute coronary syndromes. Numerous lines of evidence suggest a mechanistic link between von Willebrand factor or platelet hyperfunction and myocardial damage in patients with acute coronary syndromes. Thus, we assessed whether platelet function under high shear rates (collagen adenosine diphosphate closure times [CADP-CTs]) measured with the platelet function analyzer (PFA-100) may be enhanced in patients with myocardial infarction (MI) and whether it may predict the extent of myocardial damage as measured by creatine kinase (CK-MB) or troponin T (TnT) levels.. Patients with acute chest pain or symptoms suggestive of acute coronary syndromes (n=216) were prospectively examined at an emergency department. CADP-CT was significantly shorter in patients with MI, particularly in those with an ST-segment-elevation MI (STEMI) compared with the other patient groups (unstable angina, stable coronary artery disease, or controls). Furthermore, CADP-CT and collagen epinephrine-CT at presentation were independent predictors of myocardial damage as measured by CK-MB or TnT. Patients with MI whose CADP-CT values fell in the first quartile had 3-fold higher CK-MB and TnT levels than those in the fourth quartile.. Patients with STEMI have significantly enhanced platelet function when measured under high shear rates. CADP-CT is an independent predictor of the severity of MI, as measured by markers of cardiac necrosis. Measurement of platelet function with the PFA-100 may help in the risk stratification of patients presenting with MI.

Topics: Abciximab; Adenosine Diphosphate; Aged; Antibodies, Monoclonal; Anticoagulants; Aspirin; Cardiovascular Agents; Clopidogrel; Collagen; Comorbidity; Eptifibatide; Female; Humans; Immunoglobulin Fab Fragments; Leukocyte Count; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Myocardium; Necrosis; Peptides; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Predictive Value of Tests; Prospective Studies; Ticlopidine; Tirofiban; Tyrosine; von Willebrand Factor

Topics: Age Factors; Aged; Cardiovascular Agents; Cardiovascular Diseases; Diabetes Mellitus; Drug Prescriptions; Female; Humans; Ireland; Male; Myocardial Ischemia; Prejudice; Primary Health Care; Secondary Prevention; Sex Factors; Socioeconomic Factors

Oral antiplatelet agents (OAAs) can prevent further vascular events in cardiovascular disease. How prior use or recent discontinuation of OAA affects clinical presentation of acute coronary syndromes (ACS) and clinical outcomes (death, myocardial infarction [MI]) is unclear.. We studied and followed up for up to 30 days a cohort of 1358 consecutive patients admitted for a suspected ACS; of these, 930 were nonusers, 355 were prior users of OAA, and 73 had recently withdrawn OAA. Nonusers were at lower risk, more frequently presented with ST-elevation MI on admission, and more frequently had Q-wave MI at discharge than prior users (36.6% versus 17.5%, P<0.001; and 47.8% versus 28.2%, P<0.001, respectively). However, there was no difference regarding the incidence of death or MI at 30 days between nonusers and prior users (10.3% versus 12.4%, P=NS). In addition, prior users experienced more major bleeds within 30 days compared with nonusers (3.4% versus 1.4%, respectively; P=0.04). Recent withdrawers were admitted on average 11.9+/-0.8 days after OAA withdrawal. Interruption was primarily a physician decision for scheduled surgery (n=47 of 73). Despite a similar cardiovascular risk profile, recent withdrawers had higher 30-day rates of death or MI (21.9% versus 12.4%, P=0.04) and bleedings (13.7% versus 5.9%, P=0.03) than prior users. After multivariate analysis, OAA withdrawal was found to be an independent predictor of both mortality and bleedings at 30 days.. Among ACS patients, prior users represent a higher-risk population and present more frequently with non-ST-elevation ACS than nonusers. Although patients with a recent interruption of OAA resemble those chronically treated by OAA, they display worse clinical outcomes.

Topics: Acute Disease; Administration, Oral; Aged; Aspirin; Cardiovascular Agents; Cohort Studies; Drug Therapy, Combination; Electrocardiography; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Paris; Platelet Aggregation Inhibitors; Prospective Studies; Risk Factors; Syndrome; Thrombosis; Treatment Outcome; Withholding Treatment

To determine the extent to which cardiovascular therapies are prescribed in primary care for those with diabetes, compared with those without diabetes.. Population study of patients with and without diabetes identified using a national primary care prescribing database. All patients receiving a prescription for any diabetes therapy, including insulin and oral hypoglycaemic drugs, or diagnostic test kit for glucose ( n=8523) and those receiving no such therapies ( n=145,756) during a 1-year period (September 1999-August 2000) in the Eastern Regional Health Authority of Ireland were identified. In addition, a sub-set of patients receiving a nitrate prescription, a marker for ischaemic heart disease (IHD), were also identified ( n=14,826). Odds ratios and 95% confidence intervals for prescribing of cardiovascular therapies between those with diabetes and those without, adjusted for age and gender, were calculated using logistic regression.. The proportion of those (and 95% CES) with diabetes and IHD prescribed secondary preventative therapies was 37.3% (35.0, 39.6) for statins, 55.3% (53.0, 57.6) for angiotension converting enzyme inhibitors, 34.7% (32.5, 36.9) for beta blockers, 73.3% (71.2, 75.4) for aspirin, 4.4% (3.4, 5.4) for angiotensin-II antagonists and 2.5% (1.8, 3.2) for fibrates. The adjusted odds ratios for prescribing in those with diabetes compared with those without are 1.44 (1.30, 1.61) for statins, 3.09 (2.79, 3.42) for angiotension converting enzyme inhibitors, 0.82 (0.74, 0.91) for beta blockers, 1.23 (1.09, 1.38) for aspirin, 1.47 (1.13, 1.87) for angiotensin-II receptor blockers and 4.23 (2.88, 6.14) for lipid-lowering fibrates.. The greater rate of prescribing of cardiovascular therapies in those with diabetes relative to those without is not unexpected given the higher risk of coronary heart disease in those with diabetes. However, the proportion of patients with diabetes, particularly those with established IHD, prescribed cardiovascular therapies is considerably below that recommended in local and international guidelines.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Cardiovascular Agents; Cardiovascular Diseases; Databases, Factual; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Prescriptions; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Myocardial Ischemia; Nitrates; Pharmacoepidemiology; Primary Health Care

Circadian rhythms have long been recognized to occur in many biologic phenomena, including secretion of hormones as well as autonomic nervous system. There is increasing evidence that circadian rhythms have been also found in cardiovascular events, for example, myocardial infarction, sudden cardiac death as well as stroke have shown a circadian pattern of the distribution. Transient myocardial ischemia, detected by ambulatory ST segment monitoring, is also unevenly distributed during the day. The pathophysiology and the mechanism underlying these variations are the focus of much investigation, while it is not full understood up to date. Heart rate, blood pressure, neural and humoral vasoactive factors such as plasma norepinephrine levels and renin activity, and probably also contractility are increased in the morning hours, indicating that increase in myocardial oxygen demand contribute importantly to the increased prevalence of ischemia in the morning. Our recent study found that circadian rhythm of ischemic threshold detected by repetitive exercise treadmill tests in patients with chronic coronary artery disease is also apparently associated with levels of plasma ET-1. This information should enable better understanding as well as treatment on patients on circadian variation of cardiovascular events.

Topics: Cardiovascular Agents; Circadian Rhythm; Endothelin-1; Exercise Test; Humans; Models, Cardiovascular; Myocardial Ischemia

Previous studies have examined medication use among patients with coronary artery disease who have suffered an acute myocardial infarction (MI). However, little is known about medication use among patients with coronary artery disease who undergo percutaneous coronary intervention (PCI).. To examine the patterns of use of medical therapy among patients who undergo PCI; and to examine the determinants of medical therapy in these patients.. The Routine versus Selective Exercise Treadmill Testing after Angioplasty (ROSETTA) registry is a prospective multicentre study examining the use of functional testing after PCI. The medication use was examined among 787 patients who were enrolled in the ROSETTA registry at 13 clinical centres in five countries.. Most patients were men (mean age 61+/-11 years, 76% male) who underwent single vessel PCI (85%) with stent implantation (58%). At admission, discharge and six months, rates of acetylsalicylic acid use were 77%, 96% and 93%, respectively (discharge versus six months, P<0.0001). Rates of use of other oral antiplatelet agents were 11%, 59% and 2% (P=0.02). For individual anti-ischemic medications, rates of use were as follows: beta-blockers 49%, 58% and 59% (P<0.0001); calcium antagonists 34%, 43% and 42% (P<0.0001); and nitrates 42%, 56% and 43% (P<0.0001). Rates of use of combination anti-ischemic medications were as follows: triple therapy 7%, 9% and 9% (P<0.0001); double therapy 34%, 47% and 38% (P<0.0001); monotherapy 36%, 36% and 41% (P<0.0001); and no anti-ischemic therapy 23%, 8% and 12% (P<0.0001). Rates of use of angiotensin-converting enzyme inhibitors were 25%, 33% and 32% (P<0.0001), and rates of use of lipid lowering agents were 41%, 52% and 61% (P<0.0001).. Trials and guidelines statements have favourably affected the rates of use of acetylsalicylic acid and other antiplatelet agents after PCI. However, in spite of patients undergoing a successful revascularization procedure, physicians do not reduce the use of anti-ischemic medical therapy.

Topics: Adrenergic beta-Antagonists; Aftercare; Aged; Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Calcium Channel Blockers; Cardiovascular Agents; Coronary Disease; Drug Therapy, Combination; Drug Utilization; Exercise Test; Female; Follow-Up Studies; Humans; Hypolipidemic Agents; Male; Middle Aged; Myocardial Ischemia; Nitrates; Platelet Aggregation Inhibitors; Prospective Studies; Registries

The effects of L-cis and D-cis diltiazem on the extracellular potassium concentration ([K(+)]e), pH and cardiac function were compared in ischemic guinea pig hearts. Before inducing ischemia, L-cis diltiazem (10 and 30 microM) reduced the left ventricular developed pressure (LVDP) with a marginal inhibition of heart rate (HR), whereas lower doses of the D-cis isomer decreased both LVDP and HR. L-cis Diltiazem only slightly inhibited the increase in [K(+)]e and the decrease in pH but significantly inhibited ischemic contractures in contrast to the marked inhibition of these parameters produced by even low doses of the D-cis isomer. Notably, at equipotent doses for the ischemic parameters, L-cis diltiazem restored the left ventricular end-diastolic pressure (LVEDP) and HR after reperfusion to a greater extent than the D-cis isomer. These results suggest that the L-cis isomer may specifically improve postischemic function, in addition to the modest action on [K(+)]e and pH, in guinea pig hearts.

Topics: Animals; Atrial Function, Left; Cardiovascular Agents; Diltiazem; Dose-Response Relationship, Drug; Guinea Pigs; Isomerism; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Potassium; Up-Regulation

A possible mechanism for the action of nicorandil on the improvement of energy metabolism of ischemic/reperfused hearts was examined. Perfused rat hearts were subjected to 35-min ischemia/60-min reperfusion. The heart was treated with nicorandil at concentrations of 10 to 100 microM for the last 30-min of pre-ischemia. Nicorandil preserved the mitochondrial oxygen consumption rate during ischemia and attenuated the decrease in mitochondrial function during reperfusion in association with the enhanced post-ischemic recovery of the left ventricular developed pressure. To assess the direct effect on mitochondria, myocardial saponin-skinned bundles were incubated under hypoxic conditions in vitro. Hypoxia-induced decrease in the mitochondrial oxygen consumption rate was attenuated by treatment of the bundles with 100 microM nicorandil. This attenuation was abolished by the combined treatment with the K(ATP) channel blocker, 5-hydroxydecanoate (5-HD). These results suggest that nicorandil is capable of attenuating ischemia/reperfusion injury of isolated perfused hearts through preservation of mitochondrial function during ischemia.

Topics: Animals; Cardiovascular Agents; Cell Hypoxia; Cytochrome c Group; Energy Metabolism; In Vitro Techniques; Male; Mitochondria, Heart; Myocardial Ischemia; Myocardial Reperfusion Injury; Nicorandil; Oxygen Consumption; Rats; Rats, Wistar; Ventricular Function, Left

Low amounts of ethanol reduce cardiac damage induced by ischemia. The protection from ischemic damage by acute exposure to low amounts of ethanol in isolated myocytes and intact heart have been attributed to activation of protein kinase C (PKC). We previously found that two PKC isozymes, delta and xi, are activated by ethanol in several cell models. Here, we perfused isozyme-selective agonist and antagonist peptides that we have generated into intact heart to determine the role of these two isozymes in ethanol-induced protection from transient ischemia. Whereas xi PKC activation was required for ethanol-induced protection, delta PKC activation led to further damage. These data explain the conflicting reports on the role of acute exposure to ethanol in protection from cardiac ischemia. The clinical implications of these findings are also discussed.

Topics: Animals; Cardiovascular Agents; Enzyme Activation; Ethanol; Heart Injuries; Isoenzymes; Male; Mice; Myocardial Ischemia; Protective Agents; Protein Kinase C; Protein Kinase C-delta; Protein Kinase C-epsilon

Previous work described ATP-sensitive K(+) channel (K(ATP)) openers (e.g., BMS-180448), which retain the cardioprotective activity of agents such as cromakalim while being significantly less potent as vasodilators. In this study, we describe the pharmacologic profile of BMS-191095, which is devoid of peripheral vasodilating activity while retaining glyburide-reversible cardioprotective activity. In isolated rat hearts subjected to 25 min of global ischemia and 30 min of reperfusion, BMS-191095 increased the time to onset of ischemic contracture with an EC(25) of 1.5 microM, which is comparable to 4.7 microM and 3.0 microM for cromakalim and BMS-180448, respectively. Comparisons of cardioprotective and vasorelaxant potencies in vitro and in vivo showed BMS-191095 to be significantly more selective for cardioprotection with virtually no effect on peripheral smooth muscle, whereas cromakalim showed little selectivity. In addition to increasing the time to the onset of contracture, BMS-191095 improved postischemic recovery of function and reduced lactate dehydrogenase release in the isolated rat hearts. The cardioprotective effects of BMS-191095 were abolished by glyburide and sodium 5-hydroxydecanoate (5-HD). BMS-191095 did not shorten action potential duration in normal or hypoxic myocardium within its cardioprotective concentration range nor did it activate sarcolemmal K(ATP) current (< or =30 microM). BMS-191095 opened cardiac mitochondrial K(ATP) with a K(1/2) of 83 nM, and this was abolished by glyburide and 5-HD. These results show that the cardioprotective effects of BMS-191095 are dissociated from peripheral vasodilator and cardiac sarcolemmal K(ATP) activation. Agents like BMS-191095 may owe their cardioprotective selectivity to selective mitochondrial K(ATP) activation.

Topics: Action Potentials; Animals; Benzopyrans; Cardiovascular Agents; Cromakalim; Decanoic Acids; Dose-Response Relationship, Drug; Glyburide; Guanidines; Guinea Pigs; Heart; Heart Conduction System; Hydroxy Acids; Imidazoles; In Vitro Techniques; Male; Mitochondria; Myocardial Ischemia; Myocardial Reperfusion; Papillary Muscles; Patch-Clamp Techniques; Potassium; Potassium Channels; Rats; Rats, Sprague-Dawley; Vasodilator Agents; Vasomotor System

Simvastatin attenuates ischemia and reperfusion in normocholesterolemic animals by stabilizing endothelial nitric oxide synthase activity and inhibiting neutrophil-mediated injury. Because endothelial dysfunction is a detrimental effect of hypercholesterolemia, we examined whether short-term treatment with simvastatin could inhibit leukocyte-endothelium interaction and attenuate myocardial ischemia-reperfusion injury in apoE-deficient (apoE(-/-)) mice fed a high-cholesterol diet.. We studied leukocyte-endothelium interactions in apoE(-/-) mice fed a normal or a high-cholesterol diet after short-term (ie, 18 hours) simvastatin treatment. We also studied simvastatin treatment in myocardial ischemia-reperfusion injury by subjecting apoE(-/-) mice to 30 minutes of ischemia and 24 hours of reperfusion. ApoE(-/-) mice fed a high-cholesterol diet exhibited higher blood cholesterol levels, which were not affected by short-term simvastatin treatment. However, the increased leukocyte rolling and adherence that occurred in cholesterol-fed apoE(-/-) mice (P<0.001 versus control diet) were significantly attenuated by simvastatin treatment (P<0.01 versus vehicle). Cholesterol-fed apoE(-/-) mice subjected to myocardial ischemia-reperfusion also experienced increased myocardial necrosis (P<0.01 versus control diet), which was significantly attenuated by simvastatin (P<0.01 versus vehicle). Simvastatin therapy also significantly increased vascular nitric oxide production in apoE(-/-) mice.. Simvastatin attenuates leukocyte-endothelial cell interactions and ameliorates ischemic injury in hypercholesterolemic mice independently of lipid-lowering actions.

Topics: Animals; Anti-Inflammatory Agents; Anticholesteremic Agents; Apolipoproteins E; Cardiovascular Agents; Cell Adhesion; Cell Communication; Cholesterol; Cholesterol, Dietary; Endothelium, Vascular; Genotype; Heart Ventricles; Leukocytes; Mice; Mice, Mutant Strains; Myocardial Ischemia; Myocardial Reperfusion Injury; Neutrophils; Nitric Oxide; Simvastatin

The purpose of the following experiment was to determine whether amelioration of myocardial contractile dysfunction by diltiazem is mediated by shortening of monophasic action potential duration (MAPD) during myocardial ischemia in anesthetized dogs. Diltiazem improved regional contraction during reperfusion after 10-min occlusion. The shortening of MAPD and increase in [K+]e were blunted by treatment with diltiazem. These results suggest that shortening of action potential duration during myocardial ischemia is unlikely to be a reason for the amelioration of contractile dysfunction.

Topics: Action Potentials; Anesthesia; Animals; Cardiovascular Agents; Diltiazem; Dogs; Female; Male; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion

Nitrates are one of the most commonly prescribed drug groups for cardiac disease, especially for angina pectoris and congestive heart failure. The chronic efficacy of nitrates is limited by the development of tolerance, which can be attenuated by use of sustained-release preparations or administration of regular-release preparations asymmetrically.. To determine whether patients receiving isosorbide 5-mononitrate (ISMN) use the drug in a pharmacologically appropriate manner and whether they had been instructed in the prophylactic use of sublingual nitrates prior to effort.. We administered a questionnaire regarding details of nitrate use to 229 patients with ischemic heart disease using oral ISMN, prescribed prior to their current admission. The study was conducted in a 600-bed university-affiliated hospital.. We found that only 15% of patients receiving regular-release ISMN were taking the drug asymmetrically. In contrast, 82.6% of the patients receiving sustained-release ISMN were using the drug properly. Only 38.1% of the patients treated with regular-release ISMN were treated with the dose recommended in the literature. Furthermore, of the 190 patients who reported experiencing effort angina, only 17.9% had been instructed in the prophylactic use of nitrates prior to effort.. The majority of patients (85%) using regular-release ISMN were taking the medication in an inappropriate fashion, while most patients taking sustained-release preparations were using them properly. More than half the patients treated with regular-release ISMN were treated with doses exceeding the recommended dose. In addition, most patients experiencing effort angina had not been instructed regarding the prophylactic use of nitrates. These findings suggest that both physicians and pharmacists must be reminded of the continuing need to properly counsel patients regarding appropriate drug use.

Topics: Administration, Sublingual; Aged; Angina Pectoris; Cardiovascular Agents; Drug Prescriptions; Drug Utilization Review; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Nitrates; Surveys and Questionnaires

Potential long-term cardioprotection was investigated in an extensive experimental study. Lactobacillus cultivation components (LCC) were administered intravenously in anesthetized rats 1, 7, and 21 days before global ischemia (GI). GI was produced by full stop flow in isolated Langendorff-perfused hearts for 20 min and was followed by reperfusion. Control animals were injected with saline. LCC reduced reperfusion tachyarrhythmia significantly and improved functional recovery of the ischemized rat heart. These beneficial effects were associated with reduction of release of norepinephrine (NE) and prostacyclin at the first minute of reperfusion, activation of myocardial catalase, and overexpression of 70-kDa heat stress protein (HSP-70) at ischemia and reperfusion (P < 0.05). This cardioprotection was documented up to 21 days after a single injection of LCC. Thus Lactobacillus cultivation components are new nontoxic materials that produce marked long-term cardioprotection against ischemia-reperfusion damage. This effect is attributed to an activation of the cellular defense system, manifested by activation of the antioxidant pathway and by expression of protective proteins. NE is involved in this process, and the data also suggest a role for prostacyclin in this model of cardioprotection. The potential of LCC and related compounds working through similar mechanisms in the prevention and therapy of various ischemic heart syndromes should be explored.

Topics: Adenosine Triphosphate; Animals; Body Temperature; Cardiovascular Agents; Catalase; Coronary Circulation; Epoprostenol; Hemodynamics; HSP70 Heat-Shock Proteins; Lactic Acid; Lactobacillus; Male; Myocardial Ischemia; Norepinephrine; Pharmaceutical Preparations; Rats; Rats, Sprague-Dawley; Recovery of Function; Reperfusion Injury; Tachycardia

Cardiac troponin T (cTnT) represents a sensitive and specific marker of ischemic myocardial damage in adult and neonatal populations. The aim of this study was to detect the potential ischemic effect of persistent patent ductus arteriosus (PDA) and indomethacin treatment on the coronary vascular bed by measuring cTnT concentrations. cTnT levels were measured in 23 preterm infants (<32 weeks of gestational age) with respiratory distress syndrome (RDS), 11 with PDA and 12 without, at 2, 4, and 7 days after birth. cTnT concentrations (mean +/- SEM) significantly decreased (P<0.05) from the 2nd (0.63+/-0.09 microg/l) and the 4th (0.77+/-0.13 microg/l) to the 7th postnatal day (0.28+/-0.04 microg/l). At day 2 after birth, cTnT levels in preterm infants with RDS were significantly higher (P<0.05) than our reference values for healthy preterm neonates (0.63+/-0.09 microg/l vs. 0.18+/-0.04 microg/l). No differences were found between RDS infants with and without PDA at 2 (0.65+/-0.13 vs. 0.61+/-0.14 microg/l), 4 (0.71+/-0.21 vs. 0.87+/-0.16 microg/l), and 7 (0.26+/-0.05 vs. 0.29+/-0.07 microg/l) days of life. In infants with PDA, cTnT levels did not differ before the first dose of indomethacin was given (0.65+/-0.14 microg/l) or 2 h (0.65+/-0.15 microg/l) and 48 h (0.71+/-0.21 microg/l) afterwards.. In preterm infants with RDS the occurrence of PDA and indomethacin treatment are not associated with ischemic cardiac damage as detected by cTnT measurements.

Topics: Cardiovascular Agents; Ductus Arteriosus, Patent; Humans; Indomethacin; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Myocardial Ischemia; Respiratory Distress Syndrome, Newborn; Troponin T

The Halifax County MONItoring of trends and determinants in CArdiovascular disease (MONICA) Project found that between 1984 and 1988, the proportion of myocardial infarctions (MIs) that were fatal within 28 days remained constant, but declined between 1989 and 1993. The objective was to investigate association among case fatality, treatment and case severity of MI in hospitalized patients.. The MONICA MI register contains data on demographics, health history, in-hospital investigations, interventions and treatment, and vital status at 28 days after onset of symptoms for all MIs occurring in residents of Halifax County, aged 25 to 74 years. Logistic regression analysis was used to estimate trends in the use of cardioactive drugs and revascularization procedures. A case severity score was developed from patient characteristics at time of admission. Case fatality was calculated as the proportion of MIs that were fatal within 28 days.. Between 1984 and 1988, a large increase (OR 1.3) occurred in the use of angiotensin-converting enzyme (ACE) inhibitors, acetylsalicylic acid (ASA), thrombolysis and percutaneous transluminal coronary angioplasty (PTCA); a minor increase occurred in use of calcium channel blockers (OR=1.29, 99% CI 1.19 to 1.40); beta-blocker use decreased; case fatality remained constant and case severity score increased. From 1989 to 1993, ACE inhibitor use increased (OR=1.4, 99% CI 1.27 to 1.55); minor increases occurred in use of ASA and beta-blockers, and in PTCA and coronary artery bypass grafting; case severity did not change and case fatality decreased.. While use of beneficial treatment increased between 1984 and 1988, MI case fatality did not decrease, probably because case severity increased. Between 1989 and 1993, case severity remained constant, and the further increase in the use of beneficial therapy was associated with a decline in case fatality.

Topics: Acute Disease; Adrenergic beta-Antagonists; Adult; Aged; Angioplasty, Balloon, Coronary; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Agents; Coronary Artery Bypass; Diagnosis, Differential; Drug Utilization; Female; Hospital Mortality; Hospitalization; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Myocardial Revascularization; Nova Scotia; Risk Factors; Severity of Illness Index; Syndrome; Thrombolytic Therapy

Diltiazem has cardioprotective properties following myocardial ischemic injury. However, there are controversial results regarding the beneficial effects of diltiazem on regional myocardial flow after ischemia. Therefore, we investigated the effect of diltiazem on changes in regional myocardial flow due to ischemia for different periods. Non-radioactive colored microspheres were used for this measurement in isolated rat heart. After 20 or 40 min of global ischemia and 40 min of reperfusion, regional myocardial flow was decreased, especially in the endocardial layer. The endocardial/epicardial ratio was also decreased. The decreases in endocardial flow and the endocardial/epicardial ratio were more remarkable after 40 min of ischemia than after 20 min of ischemia. Diltiazem (10(-6) M), which was administered 15 min before ischemia, prevented only the decrease in endocardial flow and endocardial/epicardial ratio after 20 min of ischemia, whereas it did not prevent that after 40 min of ischemia. Nifedipine (2x10(-6) M) did not exert a cardioprotective effect. These findings suggested that the effect of ischemia is marked in the endocardium and, also, that the protective effect of diltiazem is seen only during a decrease in endocardial flow following short-term and reversible ischemia.

Topics: Animals; Calcium Channel Blockers; Cardiovascular Agents; Coronary Circulation; Diltiazem; Heart; Heart Rate; Heart Ventricles; In Vitro Techniques; Injections; Male; Microspheres; Myocardial Ischemia; Nifedipine; Rats; Rats, Wistar; Regional Blood Flow; Time Factors

We designed a joint research project to investigate the incidence of ischemic heart diseases in patients undergoing noncardiac surgery and to define the risk of perioperative cardiac complications in these patients. Of the 8358 surgical patients in the 8 departments of anesthesiology between March 1997 and June 1997, 328 (3.9%) had ischemic heart diseases. Among the 328 patients, 54 (16.4%) developed perioperative cardiac events, including myocardial infarction (3 patients) and either lethal or potentially dangerous dysrhythmias (51 patients). Preoperative cardiac assessments were performed while the anesthetic techniques including intensive monitoring and perioperative prophylactic therapy were also employed. Patients with ischemic heart diseases received various types of preoperative evaluation to identify the degree of coronary artery disease and to assess the overall cardiac function. The patients were monitored using a multilead electrocardiogram, an arterial line, a central venous catheter, a pulmonary artery catheter, and by transesophageal echocardiography intraoperatively. Therapeutically, isosorbide, nitroglycerin, beta-blockers, calcium channel blockers, and/or nicorandil were administered to prevent perioperative ischemia. So far, no generally accepted management strategies have been established in patients with cardiovascular disorders based on large-scale outcome trials in Japan. Therefore, nationwide large multicenter trials are awaited with interest in order to establish helpful guidelines to improve the perioperative management and to reduce ischemia in cardiac patients undergoing noncardiac surgery.

Topics: Anesthesia; Cardiovascular Agents; Humans; Incidence; Intraoperative Complications; Monitoring, Intraoperative; Myocardial Infarction; Myocardial Ischemia; Perioperative Care; Postoperative Complications; Practice Guidelines as Topic; Risk

Adenosine released during cardiac ischemia exerts a potent, protective effect in the heart via activation of A(1) or A(3) receptors. However, the interaction between the two cardioprotective adenosine receptors and the question of which receptor is the more important anti-ischemic receptor remain largely unexplored. The objective of this study was to test the hypothesis that activation of both receptors exerted a cardioprotective effect that was significantly greater than activation of either receptor individually. This was accomplished by using a novel design in which new binary conjugates of adenosine A(1) and A(3) receptor agonists were synthesized and tested in a novel cardiac myocyte model of adenosine-elicited cardioprotection. Binary drugs having mixed selectivity for both A(1) and A(3) receptors were created through the covalent linking of functionalized congeners of adenosine agonists, each being selective for either the A(1) or A(3) receptor subtype. MRS 1740 and MRS 1741, thiourea-linked, regioisomers of a binary conjugate, were highly potent and selective in radioligand binding assays for A(1) and A(3) receptors (K(i) values of 0.7-3.5 nm) versus A(2A) receptors. The myocyte models utilized cultured chick embryo cells, either ventricular cells expressing native adenosine A(1) and A(3) receptors, or engineered atrial cells, in which either human A(3) receptors alone or both human A(1) and A(3) receptors were expressed. The binary agonist MRS 1741 coactivated A(1) and A(3) receptors simultaneously, with full cardioprotection (EC(50) approximately 0.1 nm) dependent on expression of both receptors. Thus, co-activation of both adenosine A(1) and A(3) receptors by the binary A(1)/A(3) agonists represents a novel general cardioprotective approach for the treatment of myocardial ischemia.

Topics: Adenosine; Animals; Cardiovascular Agents; Cell Hypoxia; Cells, Cultured; Chick Embryo; Drug Design; Heart Atria; Heart Ventricles; Humans; Myocardial Ischemia; Purinergic P1 Receptor Agonists; Receptor, Adenosine A3; Receptors, Purinergic P1; Recombinant Proteins; Thiourea

The present study is designed to investigate the mechanism of cardioprotective effect of angiotensin II preconditioning. Isolated perfused rat heart was subjected to global ischaemia for 30 min followed by reperfusion for 120 min. Coronary effluent was analysed for lactate dehydrogenase and creatine kinase enzyme release to assess the degree of cardiac injury. Myocardial infarct size was estimated macroscopically using triphenyltetrazolium chloride staining. Four episodes of angiotensin II preconditioning markedly reduced lactate dehydrogenase and creatine kinase release in the coronary effluent and decreased myocardial infarct size. Administration of prazosin (alpha(1)-adrenoceptor antagonist) before global ischaemia reduced the extent of ischaemia-reperfusion-induced myocardial injury. Moreover, administration of prazosin during angiotensin II preconditioning or depletion of biogenic amines by reserpinisation (0.5 mg/kg i.p.) did not affect the cardioprotective effect of angiotensin II preconditioning. On the other hand, colchicine (5 mg/kg i.p.) or polymyxin B (50 microM) treatment markedly attenuated the cardioprotective effect of angiotensin II preconditioning. On the basis of these results, it may be concluded that the cardioprotective effects of angiotensin II preconditioning may be mediated through protein kinase C and may not involve release of norepinephrine or activation of alpha(1)-adrenoceptor.

Topics: Angiotensin II; Animals; Blood Pressure; Cardiovascular Agents; Colchicine; Creatine Kinase; Female; Heart; In Vitro Techniques; Ischemic Preconditioning, Myocardial; L-Lactate Dehydrogenase; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Polymyxins; Prazosin; Rats; Rats, Wistar; Reserpine; Tyramine

Carvedilol, a selective alpha(1) and non-selective beta-adrenoceptor antagonist and antioxidant, has been shown to provide significant cardiac protection in animal models of myocardial ischemia. To further explore the mechanisms contributing to the efficacy of carvedilol cardioprotection, the effects of carvedilol on hemodynamic variables, infarct size and myeloperoxidase activity (an index of neutrophil accumulation) were compared with a beta(1) selective adrenoceptor antagonist, bisoprolol. Carvedilol (1 mg/kg) or bisoprolol (1 mg/kg) was given intravenously 5 min before reperfusion. In vehicle-treated rabbits, ischemia (45 min) and reperfusion (240 min) resulted in significant increases in left ventricular end diastolic pressure, large myocardial infarction (64.7+/-2.6% of area-at-risk) and a marked increase in myeloperoxidase activity (64+/-14 U/g protein in area-at-risk). Carvedilol treatment resulted in sustained reduction of the pressure-rate-index and significantly smaller infarcts (30+/-2.9, P<0.01 vs. vehicle) as well as decreased myeloperoxidase activity (26+/-11 U/g protein in area-at-risk, P<0.01 vs. vehicle). Administration of bisoprolol at 1 mg/kg resulted in a pressure-rate-index comparable to that of carvedilol and also decreased infarct size (48.4+/-2.5%, P<0.001 vs. vehicle, P<0.05 vs. carvedilol), although to a significantly lesser extent than that observed with carvedilol. Treatment with bisoprolol failed to reduce myeloperoxidase activity in the ischemic myocardial tissue. In addition, carvedilol, but not bisoprolol, markedly decreased cardiac membrane lipid peroxidation measured by thiobarbituric acid formation. Taken together, this study suggests that the superior cardioprotection of carvedilol over bisoprolol is possibly the result of carvedilol's antioxidant and anti-neutrophil effects, not its hemodynamic properties.

Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Animals; Antioxidants; Bisoprolol; Carbazoles; Cardiovascular Agents; Carvedilol; Creatine Kinase; Disease Models, Animal; Dose-Response Relationship, Drug; Heart Rate; Isoproterenol; Lipid Peroxidation; Male; Membrane Lipids; Myocardial Ischemia; Myocardium; Peroxidase; Propanolamines; Rabbits; Reperfusion Injury; Ventricular Pressure

Because part of the cardioprotective effects of angiotensin-converting enzyme (ACE) inhibitors results from their protective effects on cardiac bradykinin (BK) metabolism, the purpose of this study was to define the metabolism of BK in normal and failing human hearts and to compare the effect of omapatrilat, a vasopeptidase inhibitor (VPI), which simultaneously inhibits both neutral endopeptidase (NEP) and ACE, with that of an ACE inhibitor. Exogenous BK at a nanomolar concentration was incubated alone, in the presence of an ACE inhibitor (ramiprilat, 36 nM), or in the presence of a VPI (omapatrilat, 61 nM) with left ventricular membranes prepared from normal donor hearts (n = 7), and hearts from patients with an ischemic (n = 11) or dilated (n = 12) cardiomyopathy (DCM). The half-lives calculated for BK alone (199 +/- 60, 224 +/- 108, and 283 +/- 122 s; P = NS) exhibited similar values for normal, ischemic, and DCM heart tissues, respectively. Ramiprilat significantly increased the half-life of BK (P <.01), but the effect was similar for the three kinds of tissues (297 +/- 104, 267 +/- 157, and 407 +/- 146 s, respectively; P = NS). The potentiating effect of the VPI omapatrilat on the kinetic parameter of BK (478 +/- 210, 544 +/- 249, and 811 +/- 349 s, respectively) was greater than that of the ACE inhibitor (P <.01). Moreover, omapatrilat had a more important potentiating effect with DCM than normal heart membranes (P <.05). These results show that not only ACE but also and mainly NEP play an important role in the degradation of BK in human heart membranes. Omapatrilat, a VPI, has a greater protective effect on BK metabolism than that of a pure ACE inhibitor. Thus, inhibition of both ACE and NEP with omapatrilat could be more cardioprotective than ACE inhibition alone.

Topics: Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Cardiomyopathy, Dilated; Cardiovascular Agents; Female; Half-Life; Heart; Humans; Male; Membranes; Middle Aged; Myocardial Ischemia; Myocardium; Neprilysin; Peptidyl-Dipeptidase A; Protease Inhibitors; Pyridines; Ramipril; Thiazepines

To perform an ecological study in an effort to generate questions concerning the preventive impact of various cardiovascular drugs on mortality from stroke and ischaemic heart disease (IHD) in the community, and to explore the association between sales of nitrates and mortality from stroke and IHD.. Out-patient drug utilization (sales) of blood pressure lowering drugs, lipid lowering drugs and nitrates were categorized in four groups of equal size by quartiles and compared with mortality from IHD and stroke, using the group of municipalities with the lowest utilization as reference, from 1989 to 1993 in 283 of Sweden's 288 municipalities, by Poisson regression. Adjustments were made for population size, age and gender proportions, the utilization rate of cardiovascular drugs other than the tested drug group and location of the municipality.. Compared with the group of municipalities with the lowest sales and adjusting only for population size, mortality from IHD and stroke increased with the extent of utilization of blood pressure lowering drugs and nitrates. In contrast, mortality decreased with increased utilization of lipid lowering drugs. After further adjustments by percentage of men, age structure, geographical location (mid-points) of the municipalities, and, as a proxy for cardiovascular disease, the sales of cardiovascular drugs other than the tested drug group, the increased risk associated with blood pressure lowering drugs disappeared, and there was a dose-response association between sales of diuretics and old antihypertensives and decreasing mortality, sales of nitrates continued to be associated with an increased risk, and the low mortality risk associated with sales of lipid lowering drugs persisted.. Lipid lowering drugs may have a preventive impact in the general population, but the preventive impact of blood pressure lowering drugs, with the exception of diuretics and old antihypertensives, may be low in many municipalities. The safety of nitrates needs more investigation at the individual level.

Topics: Antihypertensive Agents; Cardiovascular Agents; Cerebrovascular Disorders; Data Collection; Female; Humans; Hyperlipidemias; Hypertension; Hypolipidemic Agents; Male; Myocardial Ischemia; Nitrates; Sweden

Topics: Adenosine; Cardiovascular Agents; Humans; Myocardial Ischemia; Vasodilator Agents

Because coronary blood flow is impeded during systole, the duration of diastole is an important determinant of myocardial perfusion. The aim of this study was to show that coronary flow modulates the duration of diastole at constant heart rate.. In anesthetized, open-chest dogs, diastolic time fraction (DTF) increased significantly when coronary flow was reduced by lowering perfusion pressure from 100 to 70, 55, and 40 mm Hg. On average, DTF increased from 0.47+/-0.04 to 0.55+/-0.03 after a pressure step from 100 to 40 mm Hg in control, from 0.42+/-0.04 to 0.47+/-0.04 after administration of adenosine, and from 0.46+/-0.07 to 0.55+/-0.06 after L-NMMA (mean+/-SD, 6 dogs for control and adenosine, 4 dogs for L-NMMA, all P<0.05). Flow normalized to its value at full dilation and pressure of 90 mm Hg (375+/-25 mL/min) increased during the period of reduced pressure at 40 mm Hg; control, from 0.005+/-63 (2 seconds after pressure step) to 0.09+/-0.06 (15 seconds after pressure step); with adenosine, from 0.19+/-0.06 to 0. 22+/-0.06; and with L-NMMA, from 0.013+/-0.007 to 0.12+/-0.02 (all P<0.05). The increase in DTF at low pressure may be explained by a decrease in interstitial volume at low pressure, which either decreases the preload of the myocytes or reduces the buffer capacity for ions determining repolarization, thereby causing an earlier onset of relaxation.. Because the largest increase in DTF occurs at pressures below the autoregulatory range when blood flow to the subendocardium is closely related to DTF, modulation of DTF by coronary blood flow can provide an important regulatory mechanism to match supply and demand of the myocardium when vasodilatory reserve is exhausted.

Topics: Adenosine; Animals; Blood Pressure; Cardiac Pacing, Artificial; Cardiovascular Agents; Coronary Circulation; Diastole; Dogs; Enzyme Inhibitors; Heart; Muscle Relaxation; Myocardial Ischemia; Myocardium; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; omega-N-Methylarginine; Perfusion; Time Factors; Vascular Resistance

l-cis Diltiazem, an optical isomer of diltiazem, protects against myocardial dysfunction in vitro, whereas its Ca2+ channel blocking activity is about 100 times less potent than that of diltiazem. However, there is no evidence that l-cis diltiazem actually protects against ischemia/reperfusion injury in vivo. To assess this, we employed an anesthetized rabbit model, where the left circumflex artery was occluded for 15 min and reperfused for 360 min. Treatment with diltiazem before and during ischemia (bolus 200 microg/kg and 15 microg/kg per minute for 25 min, i.v.; 575 microg/kg total) showed slightly depressed hemodynamic parameters, while l-cis diltiazem (1150 microg/kg) had no effect. Treatment with l-cis diltiazem produced a high recovery of the thickening fraction and limited the infarct size in a dose-dependent manner. Furthermore, the treatment with l-cis diltiazem (1150 microg/kg) or diltiazem (575 microg/kg) 5 min before reperfusion also limited the infarct size, but not after reperfusion. These results suggest that l-cis diltiazem affects some events in the onset of reperfusion, independently of Ca2+-channel-blocking action. Our observations are the first to show that l-cis diltiazem demonstrated its cardioprotective action in the ischemic rabbit heart in vivo.

Topics: Anesthesia; Animals; Cardiovascular Agents; Diltiazem; Dose-Response Relationship, Drug; Heart; Hemodynamics; Isomerism; Male; Myocardial Infarction; Myocardial Ischemia; Rabbits; Reperfusion Injury; Time Factors

To study quality of life (QL) of patients with chronic heart failure (CHF) and QL changes resultant from mildronate therapy.. QL was studied in 30 IHD patients with CHF of NYHA class II-IV, ejection fraction > 45%; 40 IHD patients without CHF and 30 healthy subjects. CHF patients were treated for 30 days with oral mildronate (250 mg 4 times a day). QL was assessed according to the method SF-36 Health Status Survey.. QL in CHF patients is much lower than that of the controls. Objective severity of the disease and subjective satisfaction with life do not always coincide. Mildronate in a dose 1 g/day per os may be beneficial for LQ of CHF patients.. It is thought desirable to include QL in analysis of efficiency of managing patients with CHF. SF-36 is a tool able to follow up changes in QL of CHF patients within a short-term treatment period.

Topics: Administration, Oral; Adult; Cardiovascular Agents; Chronic Disease; Female; Heart Failure; Humans; Male; Methylhydrazines; Middle Aged; Myocardial Ischemia; Patient Satisfaction; Quality of Life; Stroke Volume; Treatment Outcome

1 This study investigated the effects of soluble complement receptor type 1 (sCR1) or sCR1sLex, agents which function as a complement inhibitor or as a combined complement inhibitor and selectin adhesion molecule antagonist, respectively, on the infarct size and cardiac troponin T (cTnT) release caused by regional myocardial ischaemia and reperfusion in the rat. 2 Eighty-two, male Wistar rats were subjected to 30 min occlusion of the left anterior descending coronary artery (LAD) followed by 2 h of reperfusion. Haemodynamic parameters were continuously recorded and at the end of the experiments infarct size (with p-nitro-blue tetrazolium) and cTnT release were determined. 3 Infusion of sCR1 (1, 5 or 15 mg kg-1, each n=7) or sCR1sLe(x) (1, 5 or 15 mg kg-1, n=7, 13 or 13, respectively) 5 min prior to LAD-reperfusion caused a reduction in infarct size from 59+/-2% (PBS - control, n=12) to 46+/-6%, 25+/-9% and 37+/-6% or 42+/-6%, 35+/-6% and 35+/-4%, respectively. 4 Infusion of sCR1 (15 mg kg-1, n=5) or sCR1sLe(x) (15 mg kg-1, n=5) also reduces the myocardial TnT release from 80+/-20 ng ml-1 (control) to 13+/-7 or 4+/-1 ng ml-1, respectively. 5 Thus, sCR1 or sCRsLe(x) significantly reduce infarct size and cardiac TnT release caused by 30 min of regional myocardial ischaemia and 2 h of reperfusion in the rat. The mechanisms of the cardioprotective effects of sCR1 or sCR1sLe(x) are not entirely clear, but may be due complement inhibition and/or prevention of the adhesion and activation of neutrophils.

Topics: Animals; Blood Pressure; Cardiovascular Agents; Glycosylation; Heart Rate; Hemodynamics; Male; Monocytes; Myocardial Infarction; Myocardial Ischemia; Myocardium; Oligosaccharides; Rats; Rats, Wistar; Receptors, Complement; Recombinant Proteins; Sialyl Lewis X Antigen; Troponin T

1. The potential for the N-hydroxyguanidine compound PR5 (N-(3, 4-dimethoxy-2-chlorobenzylideneamino)-N'-hydroxyguanidine) as a cardioprotective agent in heart ischaemia and reperfusion injury was investigated using rat models. 2. Administration of 1-10 mg kg-1 of PR5 5 min before 10 min of left coronary artery occlusion, followed by 20 min reperfusion, strongly inhibited reperfusion burst of arrhythmias and markedly improved the survival of the animals (e.g. ventricular fibrillation incidence 93 vs 43% (P<0.05); mortality 47 vs 0% (P<0.05), for controls and for 3 mg kg-1 of PR5, respectively). 3. Administration of 3 mg kg-1 of PR5 1 min before reperfusion to rats subjected to 10 min occlusion, 20 min reperfusion was most effective in reducing arrhythmias and decreasing mortality (43 vs 0%, P<0.05), but effects were also seen when PR5 was administered 0, 1 and 5 min after start of reperfusion. 4. Coronary occlusion/reperfusion (10 - 20 min) increased malondialdehyde (MDA) of rat hearts (0.88+/-0.13 for sham vs 1.45+/-0.12 nmol mg-1 protein for ischaemic; P<0.05). In rats where 3 mg kg-1 PR5 were administered 1 min before reperfusion the increase was attenuated (MDA being 1.04+/-0.12; P<0.05 vs ischaemic). 5. PR5 caused a substantial reduction of the infarction size in rats subjected to 180 min left coronary artery occlusion, followed by 120 min of reperfusion; the necrotic zone being 326+/-32 mg for controls vs 137+/-21 mg for animals treated with 3x3 mg kg-1 of PR5 (P<0.01). 6. PR5 reduced the elevation of the ST-segment of the ECGs, as well as caused pronounced attenuation of the rapid blood pressure drop seen at the start of reperfusion following coronary artery occlusion. 7 We conclude that the N-hydroxyguanidine PR5 provides remarkable protection against ischaemia and reperfusion induced myocardial necrosis and life-threatening arrhythmias. These effects of PR5 are discussed in relation to a recently discovered ability of N-hydroxyguanidines to function as electron acceptors at the xanthine oxidase enzyme.

Topics: Animals; Antihypertensive Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Dose-Response Relationship, Drug; Enzyme Inhibitors; Guanabenz; Guanidines; Hydroxylamines; Male; Malondialdehyde; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Oxidation-Reduction; Rats; Rats, Wistar; Reperfusion Injury; Xanthine Oxidase

1. Soybean phytoestrogens have no oestrogen agonist effects on the reproductive system and therefore it is reasonable to explore the potential of these naturally occurring plant oestrogens in the cardiovascular pathology. We therefore investigated the effects of genistein in a rat model of myocardial ischaemia-reperfusion injury. 2. Anaesthetized rats were subjected to total occlusion (45 min) of the left main coronary artery followed by 5 h reperfusion (MI/R). Sham operated rats were used as controls. Myocardial necrosis, myocardial myeloperoxidase activity (MPO), serum creatinine phosphokinase activity (CPK), serum and macrophage Tumour Necrosis Factor-alpha (TNF-alpha), cardiac intercellular adhesion molecule-1 (ICAM-1) immunostaining, cardiac mRNA for ICAM-1 evaluated by the means of reverse transcriptase polymerase chain reaction (RT - PCR), ventricular arrhythmias and myocardial contractility (left ventricle dP/dt(max)) were evaluated. 3. Myocardial ischaemia and reperfusion in untreated rats produced marked myocardial necrosis, increased serum CPK activity and MPO activity both in the area-at-risk and in the necrotic area, reduced myocardial contractility, caused ventricular arrhythmias and induced a marked increase in serum and macrophage TNF-alpha. Furthermore myocardial ischaemia-reperfusion injury increased ICAM-1 expression in the myocardium. 4. Administration of genistein (1 mg kg(-1), i.v., 5 min after coronary artery occlusion) lowered myocardial necrosis and MPO activity in the area-at-risk and in the necrotic area, decreased serum CPK activity, increased myocardial contractility, decreased the occurrence of ventricular arrhythmias, reduced serum and macrophages levels of TNF-alpha and blunted ICAM-1 expression in the injured myocardium. Finally genistein added in vitro to peritoneal macrophages collected from untreated rats subjected to myocardial ischaemia-reperfusion injury significantly reduced TNF-alpha production. 5. Our data suggest that genistein limits the inflammatory response and protects against myocardial ischaemia-reperfusion injury.

Topics: Animals; Cardiovascular Agents; Creatine Kinase; Female; Genistein; Intercellular Adhesion Molecule-1; Myocardial Ischemia; Myocardial Reperfusion Injury; Ovariectomy; Peroxidase; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha; Ventricular Function, Left

To describe risk factors associated with the development of transplantation coronary artery disease (TCAD).. A retrospective study of the Canadian experience.. Seven hundred and nineteen patients with follow-up of at least 12 months following transplantation and a minimum of one coronary angiogram were analyzed.. Two hundred and fourteen patients (30%) developed angiographic evidence of TCAD during an average follow-up of 50+/-25 months. Actuarial freedom rate from TCAD averaged 60%, and survival averaged 85% five years following transplantation. Abnormal coronary angiograms increased from 11% to 40% between the first and the fifth year following transplantation. The Cox multivariate final model showed that recipients of donor hearts of 50 years and older (RR 4.35, 95% CI 2.32 to 8.15), patients with two or more episodes of acute rejection (RR 1.56, 95% CI 1.11 to 2.21) and patients with a diagnosis of ischemic cardiomyopathy before transplantation (RR 1.38, 95% CI 1.03 to 1.84) were at higher risk of TCAD. The same risk factors also had a significant effect on survival, although patients who were administered a hepatic hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor during follow-up had a higher survival rate (95% versus 85%, P=0.01) five years following heart transplantation.. Recipients of hearts from older donors, patients with an ischemic heart disease before transplantation and those with several episodes of acute rejection are at increased risk for TCAD. Patients who are administered an HMG-CoA reductase inhibitor during follow-up have a higher survival rate five years following transplantation.

Topics: Adult; Antihypertensive Agents; Arteriosclerosis; Aspirin; Cardiovascular Agents; Cyclosporine; Cytomegalovirus Infections; Diltiazem; Female; Follow-Up Studies; Heart Transplantation; Humans; Male; Middle Aged; Myocardial Ischemia; Postoperative Care; Postoperative Complications

The myocardial infarct size (IS)-limiting effect of CP-060S, a novel cardioprotective drug that prevents Na+-, Ca2+-overload and has Ca2+ channel-blocking activity, was compared with that of diltiazem, a pure Ca2+ antagonist, to determine whether the prevention of Na+-, Ca2+-overload contributes to this IS-limiting effect. Dogs were subjected to 90 min of left circumflex coronary artery (LCx) occlusion followed by 5 h of reperfusion. Either CP-060S (300 microg/kg) or diltiazem (600 microg/kg) was administered intravenously 20 min before the occlusion. CP-060S significantly limited IS compared with that of vehicle (percentage of the area at risk: vehicle, 50.64 +/- 6.08%; CP-060S, 21.13 +/- 3.75%; p < 0.01 vs. vehicle). Although diltiazem exerted a significant decrease in rate-pressure product (RPP; an index of myocardial oxygen consumption) during occlusion equal to that of CP-060S, diltiazem did not significantly reduce IS (33.90 +/- 4.30%). Regional myocardial blood flow (RBF) was not significantly different between any of the groups. Therefore the IS-limiting effect of CP-060S cannot be explained in terms of changes in RPP or RBF. Thus the IS limitation induced by CP-060S is probably the consequence of a direct cardioprotective effect on myocytes. The prevention of Na+-, Ca2+-overload may be the primary reason for this IS-limiting effect.

Topics: Animals; Calcium Channel Blockers; Cardiovascular Agents; Dogs; Hemodynamics; Male; Myocardial Contraction; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Necrosis; Thiazoles; Thiazolidines

Activated mast cells are present in human coronary atheromas, as well as in the adventitia of patients with variant angina, and may play an important role in plaque rupture and coronary vasomotion. To assess whether or not activation of mast cells is a primary event, we measured serum levels of tryptase, a specific marker of mast cell activation, in 8 patients with unstable angina during a spontaneous ischemic episode (Group 1) and in 5 patients with variant angina (Group 2) during ergonovine-induced coronary spasm. Blood samples were collected as soon as possible after the onset of pain and ECG changes (0 min), and after 5, 15 and 60 min. Tryptase levels in Group 1 were 0.13 U/l (range 0.017-0.44) at the onset of pain and significantly raised to 0.75 U/l (range 0.05-2.49) at 5 min, decreasing to 0.076 U/l (range 0.018-0.16) at 15 min and to 0.085 U/l (range 0.01-0.25) at 60 min (p = 0.035). Conversely, tryptase levels in Group 2 were 0.09 U/l (range 0.07-0.13) at 0 min, 0.11 U/l (range 0.07-0.22) at 5 min, 0.10 U/l (range 0.07-0.18) at 15 min, 0.11 U/l (range 0.07-0.17) at 60 min (NS). In conclusion, tryptase levels raise during spontaneous ischemic episodes in unstable angina, but not after ergonovine-provoked ischemia in variant angina, suggesting that a primary, yet unknown stimulus, may activate mast cells during some ischemic episodes in unstable angina.

Topics: Aged; Angina Pectoris, Variant; Angina, Unstable; Cardiovascular Agents; Chymases; Clinical Enzyme Tests; Ergonovine; Female; Humans; Inflammation Mediators; Male; Middle Aged; Myocardial Ischemia; Radioimmunoassay; Serine Endopeptidases; Time Factors; Tryptases

Retrograde perfusion preserves ischemic myocardium when initiated shortly after coronary artery occlusion. However, benefits diminish as the delay increases. In this study, we used this technique to deliver agents known to reduce the injury associated with the reperfusion of ischemic myocardium. We proposed that the local delivery of lidocaine or L-arginine before reperfusion would reduce the damage caused during reperfusion, even after a delay between onset of ischemia and intervention designed to approximate clinical reality.. In a porcine model of myocardial ischemia, the left anterior descending coronary artery was snared immediately distal to its second diagonal branch. After 1 hour of occlusion, 34 animals were randomized into six groups: no intervention (control) (n = 6); administration of normal saline solution into the great cardiac vein (Retro-NS) (n = 6); administration of lidocaine either intravenously (i.v.-LID) (n = 6) or retrograde (Retro-LID) (n = 6); and administration of L-arginine either intravenously (i.v.-L-ARG) (n = 5) or retrograde (Retro-L-ARG) (n = 5). After 90 minutes of ischemia, the snare was released, and the myocardium was reperfused for 3 hours. Two-dimensional echocardiograms were made prior to occlusion and 60, 150, 210, and 270 minutes after occlusion. The infarct size and the area at risk were determined by lissamine green and triphenyltetrazolium chloride staining with computer planimetric quantification. Regional wall motion was assessed by a wall motion score: normal = 1; mild hypokinesia = 2.0; severe hypokinesia = 2.5; and akinesia = 3.. The area of the left ventricle at risk for infarction was similar in all groups and represented 25.4% (5.2% [standard deviation]) of the left ventricular mass (p = 0.63). The percent area of infarction in the area at risk after 3 hours of reperfusion was 76.7% (7.1% for the control group, 73.9% (5.7%) for the Retro-NS group, 72.1% (8.7%) for the i.v.-LID group, 54.5% (10.2%) for the Retro-LID group, 58.8% (4.0%) for the i.v.-L-ARG group, and 54.3% (4.0%) for the Retro-L-ARG group p < 0.005, Retro-LID and Retro-L-ARG versus Control, Retro-NS, and i.v.-LID; p < 0.03, i.v.-L-ARG versus control and Retro-NS). No significant difference in wall motion scores between groups was detected by echocardiography (p = 0.578).. Retrograde delivery of lidocaine or L-arginine before reperfusion reduces infarct size without acutely affecting wall motion after 90 minutes of ischemia and 3 hours of reperfusion. Lidocaine must be present before reperfusion to have an effect, whereas L-arginine is beneficial if it is delivered at the time of reperfusion.

Topics: Anesthetics, Local; Animals; Arginine; Cardiovascular Agents; Coloring Agents; Coronary Vessels; Echocardiography; Heart Ventricles; Image Processing, Computer-Assisted; Infusions, Intravenous; Lidocaine; Lissamine Green Dyes; Myocardial Contraction; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Reperfusion Injury; Random Allocation; Sodium Chloride; Swine; Tetrazolium Salts; Ventricular Function, Left

The aim of the present study was to determine the effect of 5-hydroxydecanoate (5-HD) on extracellular K+ levels during global ischemia for 30 min employing K+-sensitive electrodes in isolated guinea-pig hearts. 5-HD (100 microM) reduced the K+ accumulation during the early period of ischemia, but did not inhibit the elevation of extracellular K+ in the latter half of the ischemic period which was selectively enhanced by ouabain (3 microM). Thus, 5-HD appears to exert a similar mode of action as glibenclamide on extracellular K+ accumulation in the ischemic guinea-pig hearts. The present study also strengthens the previous conclusion that an ATP-sensitive K+ channel contributes only to the initial increasing phase of extracellular K+ accumulation during ischemia in guinea-pig hearts.

Topics: Animals; Cardiovascular Agents; Decanoic Acids; Guinea Pigs; Heart; Hydroxy Acids; In Vitro Techniques; Male; Myocardial Contraction; Myocardial Ischemia; Myocardium; Ouabain; Potassium; Potassium Channel Blockers

Topics: Angina, Unstable; Cardiovascular Agents; Diagnosis, Differential; Electrocardiography; Humans; Military Personnel; Myocardial Ischemia; Prognosis; Risk Factors; Russia

A total of 502 patients presenting in Utsunomiya city and its suburbs during a 10-year period were studied to determine the clinical features of ischemic heart disease and to identify coronary risk factors. The male/female ratio was 1.21, but the ratio decreased with increasing age. The duration of chest pain showed a continuous spectrum between angina and infarction, with a short duration of chest pain not being useful for excluding the diagnosis of myocardial infarction. Hypertension was more common than hypercholesterolemia in this study, although the prevalence of the latter increased slightly with time, along with the shift towards a modernized occupational pattern. Smoking was a more important risk factor for ischemic heart disease in younger individuals than in the elderly, and diabetes mellitus was highly associated with the development of myocardial infarction. The incidence of radiologically diagnosed cardiac hypertrophy and aortic calcification decreased over time. These changes may have resulted in part from improved blood pressure control and the development of new anti-hypertensive and cholesterol-lowering agents.

Topics: Age Factors; Alcohol Drinking; Aortic Diseases; Arteriosclerosis; Calcinosis; Cardiomegaly; Cardiovascular Agents; Chest Pain; Comorbidity; Death, Sudden, Cardiac; Diabetes Mellitus; Female; Humans; Hypercholesterolemia; Hypertension; Japan; Male; Morbidity; Myocardial Ischemia; Occupations; Risk Factors; Smoking; Urban Population

Adenosine has been shown to modulate myocardial intermediary metabolism. The purpose of this study was to determine whether adenosine-mediated attenuation of in vivo myocardial stunning is associated with improved myocardial phosphorylation potential. Adult, open chest pigs were subjected to 10 minutes of regional myocardial ischemia and 90 minutes reperfusion. Regional ventricular function was assessed by measuring systolic wall thickening. Myocardial phosphorylation potential was estimated from the tissue (CrP/CrxPi) ratio determined in rapid-frozen tissue biopsy samples from normal and stunned myocardium. Control pigs were compared to animals treated prior to ischemia with intracoronary adenosine (50 micrograms/kg/min). Postischemic regional systolic wall thickening in adenosine treated pigs was significantly improved (40 +/- 3% of preischemic values) compared to control untreated pigs (26 +/- 3%). Myocardial stunning was associated with decreased ATP levels, but neither the total creatine pool (CrP + Cr) nor the (CrP/CrxPi) ratio was reduced. Adenosine pretreatment was associated with decreased Pi and Cr contents resulting in improved postischemic (CrP/CrxPi) ratio in the stunned bed compared to controls, but this effect occurred only after postischemic function had attained maximal improvement. These results suggest that adenosine attenuation of in vivo myocardial stunning is independent of elevated myocardial phosphorylation potential.

Topics: Adenosine; Animals; Cardiovascular Agents; Female; Heart; Hemodynamics; Male; Myocardial Ischemia; Myocardial Reperfusion; Myocardial Stunning; Myocardium; Phosphates; Phosphocreatine; Phosphorylation; Swine

Treatment of acute myelogenous leukemia is challenging in the setting of ischemic heart disease because anthracycline and anthracenedione drugs used in induction chemotherapy may potentiate myocardial dysfunction. We have managed two patients with coincident acute myelogenous leukemia and ischemic heart disease with the cardioprotectant drug dexrazoxane (ICRF-187), administered before each dose of mitoxantrone or idarubicin. Both patients tolerated their induction chemotherapy, developed marrow hypoplasia from chemotherapy, and achieved clinical remission. Dexrazoxane may have a role as a cardioprotectant in the treatment of select patients with acute myelogenous leukemia.

Topics: Adult; Aged; Cardiovascular Agents; Humans; Leukemia, Myeloid, Acute; Male; Myocardial Ischemia; Razoxane

To characterize KC 12291 (1-(5-phenyl-1,2, 4-thiadiazol-3-yl-oxypropyl)-3-[N-methyl-N-[2-(3,4-dimethoxy phenyl) ethyl] amino] propane hydrochloride), a newly synthezised inhibitor of voltage-gated Na+ channels, the effects of the agent on Na+ current and ischemia-induced Na+ overload were investigated in isolated cardiomyocytes, atria and saline-perfused hearts. As measured by the patch clamp technique, KC 12291 (1 microM) significantly reduced peak Na+ current after activation of voltage-gated Na+ channels in rat cardiomyocytes. Partial depolarization enhanced the inhibitory effects during steady state conditions of the channel. In isolated guinea pig atria, 1 microM KC 12291 had no effect on contractility under basal conditions but effectively delayed the onset and reduced the extent of anoxic contracture. The concentration-response curve was clearly shifted to the left when atria were partially depolarized by increased extracellular K+. As measured by 23Na NMR spectroscopy in isolated perfused guinea pig hearts, intracellular Na+ rose more than four-fold in a linear fashion during 60 min of low-flow ischemia. KC 12291 (1 microM) prevented Na+ overload within the initial 12 min of ischemia; thereafter the slope of Na+ accumulation was identical to controls. Electrical excitability of hearts, evaluated by intracardial ECG, completely ceased within 15 min after the onset of ischemia. KC 12291 (1 microM) accelerated this process by more than 6 min. The data provide first evidence that KC 12291 reduces Na+ influx through voltage-gated Na+ channels during ischemia and thus delays Na+ overload by enhancing the inexcitability of the heart.

Topics: Animals; Cardiovascular Agents; Electric Stimulation; Electrocardiography; Female; Guinea Pigs; Heart; Heart Atria; Heart Ventricles; Hypoxia; In Vitro Techniques; Ion Channel Gating; Male; Membrane Potentials; Myocardial Contraction; Myocardial Ischemia; Myocardium; Oxygen; Patch-Clamp Techniques; Perfusion; Rats; Rats, Wistar; Sodium; Sodium Channels; Thiadiazoles

The novel blocker of voltage-gated Na+ channels KC 12291 (1-(5-phenyl-1,2,4-thiadiazol-3-yl-oxypropyl)-3-[N-methyl-N- [2-(3,4-dimethoxyphenyl)ethyl] amino] propane hydrochloride) delays myocardial Na+ overload in ischemia. To test whether KC 12291 displays cardioprotective properties in the intact heart, cardiac function, energy status and intracellular pH (31P NMR) as well as ion homeostasis (23Na NMR) were investigated during low-flow ischemia (100 microl/min for 36 min) followed by reperfusion. In the well-oxygenated, isolated perfused guinea pig heart, KC 12291 (1 microM) had no effect on left ventricular developed pressure (LVDP; 54+/-19 mmHg). KC 12291 delayed the onset and decreased the extent of ischemic contracture and markedly improved the recovery of LVDP in reperfusion [39+/-14 mmHg (n=4) vs 2+/-2 mmHg in controls (n=5)]. KC 12291 did not influence the rapid drop in phosphocreatine (PCr) following onset of ischemia but attenuated the decline in ATP. It also diminished the ischemia-induced fall in intracellular pH [6.39+/-0.2 (n=6) vs 6.18+/-0.20 in controls (n=6)]. In reperfusion, KC 12291 remarkably enhanced the recovery of PCr (84.8+/-9.6% vs 51.1+/-8.8% of baseline) and ATP (38.2+/-12.9% vs 23.7+/-9.3% of baseline). It also accelerated the recovery of intracellular pH. KC 12291 not only reduced the extent of ischemia-induced Na+ overload, but also enhanced Na+ recovery. It is concluded that KC 12291 delays contracture and reduces ATP depletion and acidosis in ischemia, and markedly improves the functional, energetic and ionic recovery in reperfusion. Blocking voltage-gated Na+ channels in ischemia to delay Na+ overload may thus constitute a promising therapeutic approach for cardioprotection.

Topics: Adenosine Triphosphate; Animals; Blood Pressure; Cardiovascular Agents; Energy Metabolism; Guinea Pigs; Heart; Hydrogen-Ion Concentration; In Vitro Techniques; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Phosphocreatine; Sodium; Thiadiazoles; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Cardiovascular Agents; Drug Stability; Drug Storage; Greenhouse Effect; Humans; Myocardial Ischemia; Temperature

We determined the influence of angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism on the extent of myocardial ischemia in patients with acute myocardial infarction.. The I/D polymorphism, which in part controls plasma and tissue expression of ACE, has been implicated in predisposition to myocardial infarction and ventricular remodeling.. I/D genotyping, predischarge adenosine-thallium-201 perfusion tomography and radionuclide angiography were performed in 113 patients (72 men, 41 women) with a diagnosis of acute myocardial infarction. A subgroup of 96 patients also underwent coronary angiography.. Genotypes DD, ID and II were present in 27, 56 and 30 patients, respectively. There was no significant difference in the baseline characteristics of patients, total creatine kinase, peak MB fraction, Killip class, mean ejection fraction or the number of diseased vessels in patients with the DD, ID or II genotype. However, the size of the total and the reversible perfusion defects was greater in those with DD than in those with ID or II genotype (total defect size [mean +/- SD] 33.7 +/- 22.5%, 29.5 +/- 19.2% and 22.2 +/- 16.0%, respectively [p = 0.022]; reversible defect size 18.0 +/- 16.0%, 12.1 +/- 11.6% and 8.2 +/- 7.8%, respectively [p = 0.006]). Occlusion of the infarct-related artery was also more common in patients with DD genotype (odds ratio 3.9, 95% confidence interval 1.4 to 11.0). Multivariate analysis showed that the I/D genotype was an independent predictor of perfusion defect size and patency of the infarct-related artery (p = 0.001).. DD genotype was associated with a larger ischemic defect and occlusion of the infarct-related artery. Patients with DD genotype, having a larger ischemic defect, are expected to be at a greater risk for subsequent cardiovascular events.

Topics: Adenosine; Cardiovascular Agents; Coronary Vessels; Female; Gene Deletion; Genotype; Humans; Male; Middle Aged; Myocardial Ischemia; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Radionuclide Angiography; Thallium Radioisotopes; Vascular Patency

To determine the clinical effect of diltiazem on the metabolism of adenosine, and its importance in ischemic heart disease, arterial plasma concentrations of the purine metabolites were determined in 21 healthy volunteers (10 female and 11 male) and 19 patients with effort angina (8 female and 11 male) before, during, and immediately after standard treadmill exercise tests conducted before and after they had taken 60 mg diltiazem (Cardizem; Hoechst Marion Roussel, Laval, QC, Canada) four times a day for 1 week. The results showed that the cardiac patients had significantly lower mean plasma concentrations of uric acid (46.82 +/- 25.51 versus 95.47 +/- 35.41 micrograms/ml, p 0.05), inosine (0.25 +/- 0.19 versus 0.84 +/- 0.17 microgram/ml, p < 0.05), and hypoxanthine (0.28 +/- 0.35 versus 0.50 +/- 0.27 microgram/ml, p < 0.05). Diltiazem decreased the mean resting plasma concentrations of uric acid in patients (uric acid 43.47 +/- 22.26 versus 46.82 +/- 25.51 micrograms/ml, p < 0.05) and healthy volunteers (uric acid 85.68 +/- 26.71 versus 95.47 +/- 35.41 micrograms/ml, p < 0.05). There was no statistically significant change in the plasma concentrations of the purine metabolites during exercise (p < 0.05). Female subjects had significantly lower plasma concentrations of uric acid than males (patients, 34.87 +/- 26.93 versus 55.78 +/- 21.25 micrograms/ml; healthy volunteers, 84.79 +/- 32.07 versus 104.22 +/- 37.05 micrograms/ml; p < 0.05 for both). Results of the study suggest that normal therapeutic doses of diltiazem may modulate the metabolism of adenosine and that some of the purine metabolites may be useful markers for specific types of ischemic heart disease.

Topics: Adenosine; Adult; Cardiovascular Agents; Diltiazem; Female; Guanosine; Humans; Hypoxanthine; Inosine; Male; Myocardial Ischemia; Purines; Uric Acid; Xanthine; Xanthines

Topics: Aged; Angina Pectoris; Calcium Channel Blockers; Cardiovascular Agents; Chronic Disease; Delayed-Action Preparations; Diltiazem; Drug Evaluation; Female; Hemodynamics; Humans; Male; Middle Aged; Myocardial Ischemia; Physical Exertion; Time Factors

Cardiomyocytes isolated from rabbit hearts were preconditioned in vitro by 10 min of ischemia or treatment with 100 microM adenosine. Protection was assessed as average integrated mortality following osmotic swelling and determination of viability by trypan blue exclusion over 60-180 min ischemia. Repetitive sub-maximal stimulations with 1 microM adenosine amplified the protective response. Treatment with adenosine only at the onset of prolonged ischemia afforded a dose-dependent protection. The PKC inhibitor calphostin C (500 nm) blocked preconditioning and, when added during ischemic incubation of non-preconditioned cells, significantly increased injury. The memory of adenosine-induced preconditioning decayed over a 60 min post-incubation period. Light activation of calphostin C initially added to preconditioned ischemic cells in the dark indicated that a 10 min period of PKC activity at the onset of ischemia affords full protection. The reversible PKC inhibitors chelerythrine (5 microM) or staurosporine (100 nM) added only to bracket induction of ischemia, reduced but did not abolish protection. Protection was abolished when either drug was present during induction and a subsequent 30 min post-incubation period. Staurosporine included during initiation and post-incubation but washed out in the final 5 min of post-incubation allowed significant protection to occur. It is concluded that a single adenosine receptor-stimulation induces protection as it preconditions, and PKC activity appears to be required for both induction and protection. Memory may reside in post-receptor amplification of an initial protective response.

Topics: Adenosine; Alkaloids; Animals; Benzophenanthridines; Cardiovascular Agents; Cells, Cultured; Enzyme Activation; Enzyme Inhibitors; Heart; Ischemic Preconditioning, Myocardial; Myocardial Ischemia; Myocardium; Naphthalenes; Phenanthridines; Protein Kinase C; Rabbits; Staurosporine

We examined the in vitro preconditioning effect of non-toxic derivative of endotoxin, monophosphoryl lipid A (MLA) in adult rat cardiac myocytes. Cultured 5-7-day-old myocytes were preconditioned for 4 h by treatment with 200 ng/ml MLA. Twenty h later, cells were subjected to simulated ischemia by incubation in 0.75 mm sodium hydrosulfite, 12 mM KCl, 20 mM dl-lactic acid and 10 mM 2-deoxy-D-glucose (pH 6.5) for 2 h. MLA caused a significant reduction in the levels of LDH from 286+/-8 units/l in controls to 165+/-5 units/l (mean+/-s.e.m.; P<0.0001). Similarly, CK significantly decreased from 104+/-3.1 in controls to 85+/-1.4 U/l (P<0.001). Western blot analysis indicated a significant accumulation of 72 kD heat shock protein in MLA treated as compared to control cells. No changes in 27, 32, and 90 kD heat shock proteins were discernible in the MLA treated group. These data suggest a significant "anti-ischemic" effect of MLA in myocytes that is accompanied by induction of 72 kD heat shock protein.

Topics: Animals; Cardiovascular Agents; Cells, Cultured; Gene Expression Regulation; Heart; Heat-Shock Proteins; HSP72 Heat-Shock Proteins; Ischemic Preconditioning, Myocardial; Lipid A; Myocardial Ischemia; Myocardium; Rats

The peroxidative processes and individual antioxidant protection were measured in patients with different cardiovascular diseases. We concluded that monitoring of this system we were able to detect not only the actual changes of lipid peroxidation and antioxidant defence mechanisms, but additionally the therapeutic efficacy of the treatment.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Antioxidants; Cardiovascular Agents; Catalase; Fibrinolytic Agents; Follow-Up Studies; Free Radicals; Glutathione; Glutathione Peroxidase; Humans; Hypertension; Hypolipidemic Agents; Lipid Peroxidation; Malondialdehyde; Myocardial Infarction; Myocardial Ischemia; Nitrates; Reactive Oxygen Species; Superoxide Dismutase; Thrombolytic Therapy; Treatment Outcome

The pathological increase of oxygen free radical generation has already been recognised in more than one hundred diseases. To gain information about the consequences of oxidative stress the investigation of plasma antioxidants seems to be plausible. In our study we used a new kit (RANDOX, England) for measurement of total antioxidant status (TAS) to determine whether it has diagnostic value in comparison with our earlier results of measuring other parameters of oxidative stress in the following diseases: i./In the group of patients with ischemic heart disease (n = 19) the TAS elevated from 1.08 +/- 0.13 to 1.16 +/- 0.11 mM after 2 weeks of cardioprotective drug administration showing the beneficial effect of drug treatment. ii./In the group of patients with essential hypertension (n = 47) its values were below the normal range (1.11 +/- 0.15 mM) at the time of the first investigation and increased gradually following antihypertensive treatment. iii./The changes of TAS values of patients who underwent open (n = 21) or laparoscopic (n = 21) cholecystectomy indicated the less surgical trauma following laparoscopic procedures. Our results suggest that determination of TAS is a valuable and reproducible method to detect the actual antioxidant status in patients.

Topics: Antihypertensive Agents; Antioxidants; Blood; Cardiovascular Agents; Cholecystectomy; Cholecystectomy, Laparoscopic; Humans; Hypertension; Myocardial Ischemia; Oxidative Stress; Reactive Oxygen Species; Reproducibility of Results; Stress, Physiological

Topics: Adult; Arteriosclerosis; Cardiovascular Agents; Female; Humans; Hypertension; Male; Middle Aged; Myocardial Ischemia

This study was designed to examine the plasma levels of B-type or brain natriuretic peptide (BNP), as well as A-type or atrial natriuretic peptide (ANP) in patients with unstable angina as compared with those in patients with stable exertional angina and control subjects. We measured the plasma levels of BNP and ANP in 33 patients with unstable angina, 20 patients with stable exertional angina, and 20 control subjects. The plasma levels of BNP were significantly increased in patients with unstable angina compared with those in patients with stable exertional angina and control subjects, respectively (39.5 +/- 29.4 pg/ml vs 15.1 +/- 8.0 pg/ml; p < 0.01 and 39.5 +/- 29.4 pg/ml vs 10.3 +/- 6.4 pg/ml; p < 0.01, respectively). On the other hand, there was no significant difference in the plasma levels of ANP among the three groups. Furthermore, in patients with unstable angina, the plasma levels of BNP decreased significantly after the medical treatment (from 39.5 +/- 29.4 pg/ml to 15.8 +/- 11.0 pg/ ml; p < 0.01), whereas the plasma levels of ANP did not change. We conclude that the plasma levels of BNP are increased in the majority of patients with unstable angina and that the increased levels decrease toward normal after treatment.

Topics: Adult; Aged; Angina Pectoris; Angina, Unstable; Atrial Natriuretic Factor; Cardiovascular Agents; Echocardiography; Electrocardiography; Electrocardiography, Ambulatory; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Physical Exertion

We hypothesized that microvascular reserve is a better indicator of the extent of viable myocardium postinfarction than contractile reserve, especially in the presence of a residual stenosis of the infarct-related artery.. Fifteen dogs with various infarct sizes were studied after reperfusion. Contractile reserve, studied by use of dobutamine echocardiography, and microvascular reserve, studied by use of myocardial contrast echocardiography, were measured both before and after creation of a stenosis. In the absence of a stenosis, the relation between infarct size, expressed as percent of risk area, and wall thickening improved with increasing doses of dobutamine (r = .41, .71, and .90 for 5, 10, and 15 micrograms.kg-1.min-1, respectively; P < .01 for dobutamine 15 micrograms.kg-1.min-1). In the presence of a stenosis, however, the relation was poor for all doses of dobutamine (r = .22, .57, and .32 for 5, 10, and 15 micrograms.kg-1.min-1, respectively; P < .01 for 15 micrograms.kg-1.min-1 dobutamine in the absence of a stenosis). There was a fair correlation between infarct size and perfusion defect size on myocardial contrast echocardiography after reperfusion (r = .82), with the defect size underestimating infarct size by approximately 20%. This relationship improved (P < .01) during infusions of both adenosine (r = .99) and dobutamine (r = .94) in the absence of a stenosis. The correlations between infarct size and perfusion defect on myocardial contrast echocardiography also remained good in the presence of a stenosis (r = .95 and .81 for adenosine and dobutamine, respectively; P = NS compared with stenosis).. Microvascular reserve is superior to contractile reserve for definition of the spatial topography of necrosis and hence the extent of viable myocardium within the infarct bed after reperfusion, particularly when a residual stenosis is present in the infarct-related artery.

Topics: Adenosine; Animals; Cardiotonic Agents; Cardiovascular Agents; Contrast Media; Coronary Circulation; Coronary Disease; Dobutamine; Dogs; Echocardiography; Microcirculation; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion; Salvage Therapy

Myocardial injury following ischemia and reperfusion is increased in the aging heart. The mechanisms underlying the increased susceptibility of the aging heart to ischemic injury remain unknown. We investigated whether decreased glycogen utilization with a more rapid depletion of ATP occurred during ischemia in the aging heart. Isolated buffer-perfused hearts from adult (6 months old) and aging (24 months old) Fischer 344 rats were subjected to 0, 2, 5, 10, 15 or 25 min of global stop-flow ischemia following a 15 min equilibration period (n = 5-6 for each ischemic time at each age). ATP level were decreased at preischemic baseline in aging hearts. ATP levels remained lower in the aging heart throughout ischemia (P < 0.001) with a similar pattern of decrease in both age groups. The decrease in tissue glycogen and increase in lactate contents was similar during ischemia in both age groups, suggesting that comparable glycogen utilization occurred during ischemia in adult and aging hearts. ATP catabolism leads to ADP, AMP and then adenosine. Tissue levels of adenosine, an important cardioprotective metabolite, were measured during ischemia. Tissue adenosine levels were decreased by 50% in the aging heart at 5 and 10 min, and remained depressed at 15 min and 25 min of ischemia compared to adult controls. Thus, increased ischemic injury in the aging heart is not related to differences in glycogen consumption. Lower tissue ATP levels and decreased adenosine levels were observed during ischemia. The differences in ATP content between adult and aging hearts occurred only during early ischemia and are unlikely to provide a mechanism for the increased damage observed following more prolonged periods of ischemia in the aging heart. The potential contribution of these decreases in tissue adenosine content to the increased injury observed in the aging heart will require further study.

Topics: Adenosine; Adenosine Triphosphate; Aging; Animals; Cardiovascular Agents; Glycogen; Male; Myocardial Ischemia; Rats; Rats, Inbred F344

Advances in myocardial preservation techniques and immunosuppressive drug therapy have resulted in heart transplantation as an acceptable treatment for end-stage heart failure. However, excessive periods of global myocardial ischemia followed by reperfusion can progress to irreversible graft injury. It has been reported that cyclosporine A (in addition to its well-characterized immunosuppressive actions) can blunt certain features of ischemia and reperfusion injury. This study was performed to examine the ability of cyclosporine A to attenuate such injury in a model of heart transplantation.. Twenty rabbit heterotopic transplants were divided into four study groups: (1) 30-minute ischemic control hearts; (2) 30-minute ischemic cyclosporine A-treated hearts; (3) 4-hour ischemic control hearts; and (4) 4-hour ischemic cyclosporine A-treated hearts. A single dose of cyclosporine A (10 mg/kg intravenously) or vehicle was administered to both the donor and recipient rabbits 45 minutes before heart explantation and heart transplantation, respectively.. After transplantation and 30 minutes of reperfusion, the 4-hour ischemic control hearts showed a significant (p < 0.01) leftward shift in the left ventricular end-diastolic pressure versus left ventricular volume curve compared with the 30-minute ischemic control hearts. This finding represents higher end-diastolic pressures and incomplete diastolic relaxation caused by ischemia and reperfusion. Cyclosporine A administration to the donor and recipient rabbits resulted in a significant improvement (p < 0.01) in diastolic relaxation (shift in the left ventricular end-diastolic pressure versus left ventricular volume curve back to the right) compared with 4-hour ischemic control hearts. Cyclosporine A-treated hearts also showed significant improvements in the rate of diastolic pressure fall (p < 0.05) and tau (the isovolumetric pressure decay constant) (p < 0.01) compared with ischemic control hearts.. These results indicate that single doses of cyclosporine A to both the donor and recipient inhibit the dysfunction in extent and rate of left ventricular relaxation caused by prolonged global ischemia and reperfusion. Possible mechanisms for cyclosporine A's myocardial protective actions are presented in the discussion.

Topics: Animals; Blood Pressure; Body Fluids; Cardiovascular Agents; Cyclosporine; Disease Models, Animal; Heart Transplantation; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Rabbits; Time Factors; Transplantation, Heterotopic; Ventricular Function, Left

This study compared the effects of adenosine (Ado) on the coupling of glycolysis and glucose oxidation and on mechanical function in normal hearts and in hearts subjected to transient ischemia. Isolated working rat hearts were perfused with Krebs containing 1.2 mM palmitate and 100 microU/ml insulin. After 15 min of aerobic perfusion, hearts underwent either two cycles of 10 min of ischemia and 5 min of reperfusion (stressed) or 30 min of aerobic perfusion (control). After 45 min, hearts underwent either aerobic perfusion for 35 min (series A) or 30 min of ischemia and 30 min of reperfusion (series B). In series A, left ventricular minute work (LV work) was similar in control and stressed hearts and was not affected by Ado (500 microM) or N6-cyclohexyladenosine (CHA 0.5 microM). Ado reduced glycolysis by 49% in control hearts but increased glycolysis by 74% in stressed hearts. CHA inhibited glycolysis in both groups by 50 and 62%, respectively. In series B, LV work during reperfusion recovered to a similar extent in untreated control and stressed hearts. In control hearts, Ado reduced glycolysis by 50% while enhancing LV work to 81% of preischemic values. In stressed hearts, Ado increased glycolysis by 34% and depressed LV work to 9%, whereas CHA inhibited glycolysis by 53% and LV work to 91%. These data indicate that coupling of glycolysis to glucose oxidation is a key determinant of mechanical function of the postischemic myocardium. They also show that the metabolic and protective effects of Ado depend on the status of the heart before sustained ischemia.

Topics: Adenosine; Animals; Cardiovascular Agents; Glycogen; Glycolysis; Myocardial Ischemia; Myocardial Reperfusion; Rats; Rats, Sprague-Dawley; Stress, Physiological; Ventricular Function, Left

When no anaesthetic is used, even 3-5 short-term disturbances of the myocardium supply with blood (during a few days) are enough for its initial necrosis and for damage of its vascular bed. In acute experiments on rats rutin discovers the ability to resist such damages, but on the chronic model of stenocardia in dogs its therapeutic effect can be found only under conditions of limitation of the ischemic effect by purposefully chosen complex medicinal therapy.

Topics: Anesthesia; Angina Pectoris; Animals; Cardiovascular Agents; Coronary Vessels; Disease Models, Animal; Dogs; Drug Evaluation, Preclinical; Heart; Myocardial Ischemia; Myocardium; Necrosis; Rats; Rutin; Time Factors

Topics: Cardiovascular Agents; Coronary Artery Bypass; Humans; Myocardial Infarction; Myocardial Ischemia; Prognosis; Quality of Life

Hemosorption and plasmapheresis were studied for effects on lipid peroxidation, antioxidant blood activity, platelet hemostasis, microcirculation, myocardial contractility and intracardiac hemodynamics. The results demonstrated that antioxidant blood response is a key criterion responsible for decreased efficacy of hemosorption and plasmapheresis in patients with progressive angina pectoris with chronic heart failure. The results of hemosorption and plasmapheresis in the above patients may become better if an adjuvant antioxidant therapy is used.

Topics: Angina Pectoris; Cardiovascular Agents; Chronic Disease; Combined Modality Therapy; Drug Therapy, Combination; Evaluation Studies as Topic; Female; Heart Failure; Hemoperfusion; Humans; Male; Myocardial Ischemia; Physical Exertion; Plasmapheresis

Topics: Angina Pectoris; Cardiovascular Agents; Coronary Artery Disease; Coronary Disease; Drug Evaluation; Humans; Myocardial Ischemia

Topics: Cardiovascular Agents; Coronary Artery Disease; Humans; Myocardial Ischemia

Survivors of myocardial infarction are at increased risk for another MI, congestive heart failure, ventricular arrhythmias, and sudden death. Beta blockers reduce the rate of sudden death, reinfarction, and recurrent ischemia, particularly in elderly patients. Chronic aspirin therapy has shown significant reductions in cardiovascular morbidity and mortality and is recommended for all post-MI patients who can tolerate it. ACE inhibitor therapy has shown benefit in patients with impaired LV function. Identifying post-MI patients at risk for sudden death and preventing fatal arrhythmias has proven difficult. Class I antiarrhythmics should be avoided. Amiodarone and perhaps sotalol appear promising, but large-scale trials are still ongoing.

Topics: Aged; Arrhythmias, Cardiac; Cardiovascular Agents; Death, Sudden; Heart Failure; Heart Ventricles; Humans; Myocardial Infarction; Myocardial Ischemia; Recurrence; Risk Factors; Survival Analysis

This study tests the hypothesis that the administration of cyclocreatine prior to global ischemia enhances recovery of cardiac function during reperfusion. Two models were used. First, in a Langendorff-working heart model of normothermic cardioplegic arrest, rats (n = 6 per group) were injected intravenously with saline or cyclocreatine (600, 300, or 150 mg/kg). After 30 min or 2 h, hearts were excised and perfused in the Langendorff mode for 5 min and then in the working heart mode for 20 min. Normothermic arrest was induced by infusing warm St. Thomas solution once; then hearts were kept at 37 degrees C for 40 min. Following arrest, hearts were reperfused in the Langendorff mode for 15 min and then in the working mode for 30 min. Cyclocreatine consistently produced significantly better recovery of aortic flow and cardiac output compared to that of saline hearts. Second, in an intact canine model of cold cardioplegic arrest, adult mongrel dogs (n = 3 to 6 per group) underwent aortic cross-clamping for 1 h, followed by reperfusion on bypass for 45 min and off bypass for 4 h. Dogs were injected intravenously with saline or cyclocreatine (500 mg/kg) for 1 h before experiment. Post-bypass segmental contractility and cardiac output were significantly better in cyclocreatine hearts compared to that of controls. In a limited study, after a 3 h aortic cross-clamp time, cyclocreatine hearts achieved 91% baseline function while control hearts failed after 2 h. Results of this study suggest that cyclocreatine, without inotropic or chronotropic effect, protects the heart from global ischemic injury.

Topics: Animals; Cardiac Output; Cardiopulmonary Bypass; Cardiovascular Agents; Coronary Circulation; Creatinine; Dogs; In Vitro Techniques; Male; Models, Cardiovascular; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Sodium Chloride; Time Factors

Topics: Adrenergic beta-Antagonists; Calcium Channel Blockers; Cardiovascular Agents; Coronary Disease; Humans; Intraoperative Complications; Myocardial Ischemia; Postoperative Complications

Heart rate (HR) is a major factor determining the severity of myocardial ischemia, and HR reduction is an effective therapy for myocardial ischemia. We tested the effects of HR reduction induced by either UL-FS 49 or atenolol on regional myocardial blood flow, function, and infarct size (IS) in a porcine model of 90-min low-flow ischemia and 2-h reperfusion. In 24 Göttinger miniswine, the left anterior descending coronary artery (LAD) was cannulated and hypoperfused at constant inflow to reduce anterior systolic wall thickening (AWT, sonomicrometry) by approximately 85%. Eight swine served as a placebo group, and 8 other swine received UL-FS 49 (0.60 mg/kg intravenously, i.v.) after 10-min ischemia. In the remaining 8 swine, atenolol was infused after 10-min ischemia at a dosage [mean 1.75 +/- 1.20 (SD) mg/kg i.v.] to mimic the HR reduction observed with UL-FS 49. Systemic hemodynamics, subendocardial blood flow (ENDO, microspheres) and AWT were measured under control conditions, at 10 and 90 min of ischemia. In the swine receiving UL-FS 49 or atenolol, additional measurements were made 5 min after administration of the respective drug. After 2-h reperfusion, IS (percentage of area at risk) was determined with TTC-staining. Five minutes after administration of UL-FS 49, HR was decreased from 113 +/- 9 to 83 +/- 13 beats/min (p < 0.05) and remained unchanged when ischemia was prolonged to 90 min. In the swine receiving atenolol, HR was reduced from 117 +/- 14 to 93 +/- 7 beats/min (p < 0.05) 5 min after drug administration and decreased further to 87 +/- 10 beats/min when ischemia was prolonged to 90 min. After 10 min of ischemia, AWT in the placebo, UL-FS 49, and atenolol group was decreased to 7.0 +/- 5.5, 6.4 +/- 3.5, and 6.2 +/- 3.3% (all p < 0.05 vs. control), respectively. The reduction in ENDO was also comparable among the three groups. In the placebo group, AWT remained unchanged when ischemia was prolonged to 90 min (4.4 +/- 2.6%). In swine receiving atenolol, AWT tended to increase (13.6 +/- 10.5%), whereas in swine receiving UL-FS 49, AWT was significantly increased to 21.4 +/- 7.1% (p < 0.05 vs. 10-min ischemia and vs. the placebo and atenolol groups). IS was significantly reduced in swine receiving atenolol (3.9 +/- 3.5%) or UL-FS 49 (5.8 +/- 4.6%) as compared with the placebo-group (10.4 +/- 8.9%).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adenosine Triphosphate; Animals; Atenolol; Benzazepines; Blood Pressure; Bradycardia; Cardiovascular Agents; Coronary Circulation; Disease Models, Animal; Female; Heart; Heart Rate; Injections, Intravenous; Lactates; Male; Myocardial Infarction; Myocardial Ischemia; Myocardium; Oxygen Consumption; Phosphocreatine; Reperfusion Injury; Swine; Swine, Miniature

The frequency of chronic hypertension among cardiac surgery patients implies that experimental therapies that protect normotensive myocardium will be more clinically relevant if they also protect chronically hypertensive myocardium. We tested the effectiveness of three experimental therapies that protect normotensive myocardium from ischemic injury in both normotensive (NTR) and spontaneously hypertensive (SHR) isolated Sprague-Dawley rat hearts. Post-ischemic recovery of ATP, left ventricular end diastolic pressure, developed pressure, negative and positive left ventricular dP/dt (-dP/dt and +dP/dt) and coronary flow (CF) were compared in ischemically preconditioned, adenosine-pretreated, bethanechol-pretreated and untreated NTR and SHR isolated rat hearts. The effect of time on our preparation was evaluated by comparison to NTR and SHR hearts maintained in vitro for equal duration but not subjected to an ischemic insult (N = 7, all groups). Preconditioning, adenosine and bethanechol significantly improved recovery of ATP, left ventricular end diastolic pressure, developed pressure, -dP/dt, +dP/dt and coronary flow in both NTR and SHR hearts (P < 0.001 vs. untreated, all comparisons). Although recovery was not so pronounced in SHR hearts, these results suggest that experimental therapies that protect normotensive myocardium also protect chronically hypertensive myocardium. The effect of adenosine and that of ischemic preconditioning were nearly identical, and both treatments were significantly more cardioprotective than bethanechol in both NTR and SHR hearts (P < .05 and P < .001, respectively). This result suggests that adenosine buildup is more important than muscarinic receptor stimulation as a mechanism of the protection afforded by ischemic preconditioning.

Topics: Adenosine; Adenosine Triphosphate; Animals; Bethanechol; Cardiovascular Agents; Heart; Hemodynamics; Hypertension; Male; Muscarinic Agonists; Myocardial Ischemia; Myocardium; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley

The sequence ischaemia-reperfusion is characterized by reperfusion damage. The calcium overload occurring at the beginning of reperfusion is one of the main mechanisms responsible for reperfusion damage. Ruthenium red, a blocker of the mitochondrial calcium uniport system, could prevent this damage by preserving the ATP synthesis in the mitochondria. We tested ruthenium red and another ruthenium compound, cis-tetrammine dichlororuthenium (III) chloride in our experimental model of ischaemic-reperfused rat hearts. After a 15 minute-stabilization period, the hearts were submitted to a 30 minute global ischaemia period and then reperfused for 45 minutes with the standard perfusion solution or with ruthenium red or cis-tetrammine dichlororuthenium (III) chloride at 1, 3 or 9 microM. Ruthenium red at 3 microM exerted a protective effect in our experimental conditions by showing a significant improvement of the contractility recovery at the end of reperfusion and a significant decrease of the malondialdehyde production, which reflects free radical production. The cis-tetrammine dichlororuthenium (III) chloride (containing 1 Ru ion per molecule) at 9 microM was slightly less efficient than ruthenium red at 3 microM (containing 3 Ru ions per molecule). The heart ruthenium binding was better for the ruthenium red than for the cis-tetrammine dichlororuthenium (III) chloride, suggesting a role of the ruthenium ion complexation in the crossing of the membrane, whereas the cardiac effect seemed to be linked to the ruthenium ion heart concentration, which was similar for the ruthenium red at 3 microM and for the cis-tetrammine dichlororuthenium (III) chloride at 9 microM. One can hope that ruthenium compounds would limit reperfusion damage and infarct size after ischaemia in in vivo models.

Topics: Animals; Calcium; Cardiovascular Agents; Coronary Circulation; Creatine Kinase; Free Radicals; Heart; In Vitro Techniques; Male; Malondialdehyde; Muscle Proteins; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Organ Size; Rats; Rats, Wistar; Ruthenium Compounds; Ruthenium Red

By the results of bicycle ergometry test 28 coronary heart disease (CHD) patients were divided into 2 groups: with a pronounced anginal syndrome (group 1) and coronary insufficiency evident on ECG (group 2). Vegetative and psychophysiological parameters obtained in the examinees (heart rate, arterial pressure, pain threshold, personality profile) demonstrated that increased pain sensitivity, anxiety, predisposition to neurotic reactions were more typical for patients of group 1. Therapeutic response was achieved after psychophysiological correction by means of creation and activation of artificial stable functional connections of the brain.

Topics: Adult; Aged; Angina Pectoris; Blood Pressure; Cardiovascular Agents; Diazepam; Drug Therapy, Combination; Electrocardiography; Etimizol; Exercise Test; Female; Heart Rate; Humans; Male; Middle Aged; Myocardial Ischemia; Photic Stimulation; Psychophysiology

We have characterized the coronary vascular reserve, left ventricular function and inotropic response in dogs with chronic heart failure consequent to intracoronary embolization (EMB) with 50 microns spheres. We conducted studies 12-39 months after embolization and contrasted the findings with normal (CON) dogs. Acute embolization produced sustained LV volume enlargement and increased wall thickness, reduction of LV ejection fraction and elevated end-diastolic pressures; resting catecholamine levels were also increased. Responses to phenylephrine, nitroprusside, and dobutamine were identical in CON and EMB and coronary vasodilator reserve was reduced despite larger coronary vascular volume. Analysis by light microscopy showed a diffuse focal and interstitial fibrosis distributed uniformly from endocardium to epicardium associated with 14% loss of myocytes. This created a functional separation of myocardial muscle bundles and a disruption of the syncytial nature of the heart. Electron microscopy of the areas of fibrosis revealed myocytes in states ranging from normal appearing, to ghosts with evidence of cytolysis and loss of the sarcolemma. This model of chronic congestive heart failure with LV systolic dysfunction and elevated LV diastolic pressures shares a number of features with the syndrome in humans.

Topics: Animals; Blood Flow Velocity; Cardiovascular Agents; Chronic Disease; Coronary Circulation; Coronary Vessels; Disease Models, Animal; Dogs; Echocardiography; Embolism; Heart Failure; Hemodynamics; Hyperemia; Microscopy, Electron; Myocardial Ischemia; Myocardium; Ventricular Dysfunction, Left

Prevalence of type 1 silent myocardial ischemia (SMI; completely asymptomatic patients) is reported to appear 2 to 4% of the general population. The prognosis of these patients is said to be similar to that of patients with angina pectoris. Our study investigated a 10-year follow up of silent myocardial ischemia detected by bicycle exercise testing in comparison to a comparable control group. 10 years later 127 patients were reinvestigated by bicycle ergometry, 33 patients out of the SMI-group (group A) and 84 patients out of the control group (group B). Mean age in group A was 62 +/- 7 years (range 42 to 71 years), in group B 56 +/- 7 years (range 29 to 69 years). After 10 years there was no statistical significant difference between the 2 groups on using beta-blockers, calciumchannel-blockers and nitrates, on arterial hypertension, diabetes mellitus, smoking history and positive family-history as well as in total cholesterol, HDL- and LDL-cholesterol, triglycerides, blood glucose and uric acid. 1 patient of A and 2 of B died from a sudden cardiac death, 2 of A and 7 of B survived a myocardial infarction, 11 of A and 11 of B developed angina pectoris (p < 0.05). A statistical significant difference was found in the ergometric working capacity (maximal workload in Watt) between the 2 groups (p < 0.001) that did not change over the 10 years, the control group worked better in both investigations. SMI type 1, detected by bicycle ergometry seems to be only a risk factor for developing "loud ischemia" (= angina pectoris) but not for "hard events". A routine screening of completely asymptomatic persons with bicycle ergometry seems to have no prognostic relevance.

Topics: Adult; Aged; Angina Pectoris; Cardiovascular Agents; Cause of Death; Exercise Test; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Ischemia; Survival Rate

An experimental model of myocardial ischemia/reperfusion injury was used to assess the cardioprotective effects of SC-52608, a low molecular weight superoxide dismutase mimetic. Langendorff perfused rabbit isolated hearts were subjected to 30 min of global ischemia followed by 45 min of reperfusion. Hearts perfused in the presence of 20 microM SC-52608 exhibited a decrease in the release of creatine kinase and intracellular potassium compared to hearts receiving vehicle (control). A progressive increase in left ventricular end-diastolic pressure developed upon reperfusion in all hearts, but was significantly greater in control hearts when compared to hearts treated with SC-52608 (P < 0.05). In addition, results obtained with a radiolabeled monoclonal antibody to the intracellular protein myosin, indicate an increased degree of irreversible damage in vehicle-treated hearts. Myocardial protection was not significant in an additional group of hearts treated with 10 microM SC-52608. The hemodynamic, biochemical, morphological, as well as the antimyosin binding data, demonstrate that pretreatment with SC-52608 protects the myocardium from damage associated with global ischemia and reperfusion. The mechanism by which SC-52608 mediates the observed protective effect is most likely related to its ability to scavenge superoxide.

Topics: Animals; Antibodies, Monoclonal; Antioxidants; Blood Pressure; Cardiovascular Agents; Coronary Circulation; Creatine Kinase; Free Radical Scavengers; Intracellular Fluid; Isoenzymes; Male; Microscopy, Electron; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Myosins; Organometallic Compounds; Perfusion; Potassium; Rabbits; Superoxide Dismutase; Superoxides

On the basis of 1501 "Drug Disposal Charts" a comparative analysis was carried out of treatment schemas of ischaemic heart disease and arterial hypertension used by cardiologists and regional general practitioners, taking into account the effectiveness of treatment. Besides that the frequency was analysed of the reports by doctors on adverse reactions occurring during treatment.

Topics: Ambulatory Care Facilities; Cardiac Care Facilities; Cardiovascular Agents; Humans; Hypertension; Myocardial Ischemia; Poland; Treatment Outcome

We determined whether an organic superoxide dismutase mimetic could reduce myocardial injury resulting from a 90-min occlusion of the left circumflex coronary artery, followed by 18 hr of reperfusion in an anesthetized canine. The superoxide dismutase-mimetic studied (SC-52608) was a synthetic Mn-based macrocyclic compound. SC-52608 or the inactive analog SC-54385 was administered as four doses of 4 mg/kg i.v. Drug, inactive analog or vehicle was administered 30 and 15 min before ischemia and 15 min and immediately before reperfusion. To ensure parity of left circumflex coronary artery occlusion-induced ischemia, only animals with ischemic zone blood flow of less than 0.15 ml/min/g were included in the final analysis. Ischemic zone blood flow was 0.069 +/- 0.016 ml/min/g in control animals (n = 10), 0.072 +/- 0.010 ml/min/g in SC-52608-treated animals (n = 11) and 0.053 +/- 0.011 ml/min/g in SC-54385-treated (n = 9) animals. A transient hypotensive effect was observed upon SC-52608 administration. Hemodynamic parameters were otherwise unaffected by SC-52608 or SC-54385. The areas at risk of infarct were 39.6 +/- 1.9%, 38.7 +/- 1.1% and 39.4 +/- 1.1% in control, SC-52608-treated and SC-54385-treated animals, respectively. Myocardial infarct sizes (% of area at risk of infarct) were 44.2 +/- 5.6%, 25.7 +/- 4.3% and 35.1 +/- 4.9% in control, SC-52608-treated and SC-54385-treated animals, respectively (P < .05 control vs. SC-52608-treated). Therefore, the synthetic superoxide dismutase mimetic protected the regionally ischemic and reperfused myocardium from injury, implicating oxygen-derived radicals in the tissue-injury process.

Topics: Animals; Cardiovascular Agents; Coronary Circulation; Coronary Vessels; Dogs; Hemodynamics; Male; Manganese; Molecular Mimicry; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Organometallic Compounds; Superoxide Dismutase; Survival Analysis

The effects of the specific bradycardic agent, zatebradine (UL-FS 49), on ventricular arrhythmias occurring during an acute ischemia were compared to those of verapamil. Anesthetized rabbits were submitted to a ligation of the left circumflex coronary artery for 20 min. Zatebradine (150 and 750 micrograms/kg, i.v.) dose-dependently reduced heart rate, but changed neither the left ventricular pressure nor the (+)dp/dtmax. In comparison, verapamil (150 and 750 micrograms/kg, i.v.) reduced heart rate, systemic blood pressure, left ventricular pressure and (+)dp/dtmax. The incidence of ventricular premature beats occurring during acute ischemia was changed neither by zatebradine nor by verapamil. Ventricular fibrillation, occurring in 36% of the saline-treated rabbits, was reduced to 18% in the presence of 750 micrograms/kg of zatebradine and 0% with verapamil (750 micrograms/kg, p < 0.05). The action of zatebradine on ischemia-induced ventricular fibrillation, albeit limited, was completely reversed by atrial pacing to the predrug heart rate. To further investigate the mechanisms involved in the antiarrhythmic potential of both zatebradine and verapamil, their electrophysiological actions were compared in canine Purkinje fibers. Both zatebradine and verapamil induced a dose-dependent increase in action potential duration (APD) measured at 90% repolarization. The APDs measured during the plateau level (APD30) and at 50% of the repolarization (APD50) were shortened by verapamil and increased by zatebradine showing that at the concentrations used, zatebradine did not exhibit any calcium antagonistic activity when compared to verapamil. The results of the present study suggest that the specific bradycardic agent zatebradine showed a beneficial action mainly because of its anti-ischemic properties. However, the present studies performed in anesthetized rabbits suggest that in this species pure reduction in heart rate is not sufficient to entirely prevent ischemic arrhythmias.

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Benzazepines; Cardiovascular Agents; Dogs; Dose-Response Relationship, Drug; Electrophysiology; Female; Heart Ventricles; Hemodynamics; Injections, Intravenous; Male; Myocardial Ischemia; Purkinje Fibers; Rabbits; Verapamil

Oxygen-derived free radicals are involved in myocardial reperfusion injury. In the present study MDL 74,405 (S-(-)-3,4-dihydro-6-hydroxy-N,N,N-2,5,7,8-heptamethyl-2H-1-benzo pyran-2-ethanaminium 4-methylbenzenesulfonate), a hydrophilic derivative of alpha-tocopherol, has been shown to inhibit lipid peroxidation in rat brain homogenate, ex vivo lipid peroxidation in mouse heart and to accumulate in myocardial tissue. Infused i.v. MDL 74,405 induced a dose-related reduction of myocardial infarct size in pentobarbitone-anaesthetised rats subjected to 60 min coronary artery ligation followed by 30 min reperfusion. Similarly i.v. infusion of MDL 74,405 beginning 10 min before coronary artery occlusion (60 min) until 30 min after the onset of reperfusion (8 days) caused a decrease of infarct size associated with an increase in aortic flow. Plasma levels of creatine phosphokinase were significantly reduced. In isolated infarcted hearts, obtained from MDL 74,405-treated rats after 8 days of reperfusion and perfused according to the Langendorff technique, an increase in the contractility index (+) and (-) dP/dtmax was apparent. In isolated non-infarcted rat hearts subjected to 30 min no-flow global ischaemia, perfusion with MDL 74,405 resulted in an increase in heart rate and the contractility indices (+) dP/dtmax, and left ventricular systolic pressure during reperfusion. In conclusion MDL 74,405, is a cardioselective free radical scavenger, that reduces myocardial infarct size and attenuates post-ischaemic dysfunction.

Topics: Animals; Cardiovascular Agents; Creatine Kinase; Free Radical Scavengers; Heart; In Vitro Techniques; Lipid Peroxidation; Male; Mice; Molecular Conformation; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Rats; Rats, Sprague-Dawley; Vitamin E

This investigation determined whether attenuation of the tachycardia produced by dobutamine administration would improve perfusion and function distal to a severe coronary artery stenosis.. Tachycardia adversely affects perfusion and function distal to a coronary artery stenosis. It is not known whether a specific bradycardic agent can improve blood flow and function in an ischemic zone during administration of dobutamine.. The effects of dobutamine (2, 5 and 10 micrograms/kg body weight per min) alone and in combination with zatebradine (0.5 mg/kg), a specific bradycardic agent, on hemodynamic status, segment shortening (ultrasound length transducers) and myocardial perfusion (microspheres) were studied in anesthetized dogs with severe left circumflex coronary artery stenosis.. A 50% reduction in left circumflex coronary artery blood flow (58 +/- 4 to 29 +/- 2 ml/min [mean value +/- SEM]) produced a decrease in systolic shortening in the ischemic zone. Only a dose of dobutamine that did not elevate heart rate (2 micrograms/kg per min) produced an increase in segment shortening in the ischemic zone. High doses of dobutamine (10 micrograms/kg per min) caused an increase in heart rate without improvement in function and a reduction in the subendocardial/subepicardial flow ratio (0.74 +/- 0.06 to 0.48 +/- 0.05). Zatebradine administered in the presence of dobutamine caused a decrease in heart rate, an increase in subendocardial/subepicardial blood flow ratio (0.48 +/- 0.05 to 0.78 +/- 0.09) and allowed an increase in ischemic zone segment shortening. When normalized for changes in heart rate, ischemic zone subendocardial flow increased by 123 +/- 41% (0.39 +/- 0.09 to 0.71 +/- 0.12 ml/100 g per beat). Atrial pacing abolished the effects of zatebradine.. The present data suggest that the perfusion-contraction matching that accompanies a decrease in heart rate results in enhancement of inotropic stimulation of an ischemic zone. The actions of zatebradine are related to an increase in subendocardial blood flow per beat that allows improvement of regional contractile function.

Topics: Animals; Benzazepines; Cardiovascular Agents; Coronary Circulation; Dobutamine; Dogs; Drug Synergism; Female; Heart Rate; Hemodynamics; Male; Myocardial Contraction; Myocardial Ischemia; Stimulation, Chemical

The sympathetic-adrenal and kallikrein-kinin systems were studied in 225 patients with various coronary heart diseases before and after therapy with lipoic acid (150 mg/day), tocopherol (100 mg/day), anaprilin (40 mg/day), prodectin (750 mg/day) or their combination. Myocardial and adrenal catecholamine levels were measured in experiments on animals exposed to emotional pain stress. Their levels were found to be affected by lipoic acid, tocopherol, obsidan or their combinations in the same doses, taking into account species specificity. Lipoic acid therapy for patients with coronary heart disease decreased epinephrine excretion, enhanced the elimination of vanillylmandelic acid and norepinephrine. Tocopherol lowered daily urinary epinephrine levels and increased the release of vanillylmandelic acid, without changing epinephrine excretion. Emotional pain stress resulted in myocardial epinephrine accumulation and adrenal norepinephrine in the animals. Lipoic acid prevented this accumulation, whereas tocopherol did not possess this effect.

Topics: Adolescent; Adrenal Glands; Adult; Aged; Angina Pectoris; Animals; Cardiovascular Agents; Drug Evaluation; Drug Evaluation, Preclinical; Drug Therapy, Combination; Humans; Kallikrein-Kinin System; Male; Middle Aged; Myocardial Ischemia; Neurotransmitter Agents; Pain; Rats; Stress, Psychological; Sympathetic Nervous System

Twenty-two patients with coronary heart disease (CHD) were examined for pain threshold and pain tolerance by a tourniquet test. The relationships between pain and ST segment depression were studied simultaneously during bicycle exercise. Pain sensitivity was measured in response to action of various antianginal drugs (isosorbide dinitrate, verapamil, nifedipine, diltiazem, propranolol, atenolol) and placebo. Reproducibility of the tourniquet test proved satisfactory. There were significant correlations between tourniquet test evidence and clinical patterns of ischemic myocardial episodes: significant differences in the values of pain threshold and pain tolerance in patients with painful myocardial ischemia, in combination of angina of effort with painless myocardial ischemia (p < 0.0001). Significant were also correlations between tourniquet test findings at bicycle exercise and value describing the proportion of ST depression to pain. As for the drugs, verapamil appeared most active in the tourniquet test (p < 0.02 and p < 0.05 for pain threshold and pain tolerance, respectively). Pain tolerance changes due to isosorbide dinitrate were somewhat greater than for placebo (p = 0.06). The study provided evidence in support of the adequacy of the tourniquet test for assessment of general pain sensitivity and pain sensitivity to myocardial ischemia as well as of analgetic effects of the drugs. Verapamil and isosorbide dinitrate are suggested to have analgetic activity.

Topics: Aged; Angina Pectoris; Cardiovascular Agents; Drug Evaluation; Exercise Test; Humans; Least-Squares Analysis; Male; Middle Aged; Myocardial Ischemia; Pain Measurement; Pain Threshold; Tourniquets

The examination of 208 patients with stable exercise-induced angina has demonstrated that the long-term (12 weeks and 12 months) antianginal effect can be predicted with a high accuracy from the results of acute pair exercise test using the drugs. The negative result of the test with verapamil is not informative due to the accumulation of its antianginal effect when the agent is used long. The long-term antianginal effect of nitrosorbide is determined not only by positive pair exercise test, but mainly by its dosage regimen during a day. The fact that half the patients who took labetalol for a long time developed tolerance to its anginal effect casts some suspicion on the advisability of its administration in stable angina. Lipid peroxidation as a mechanism of platelet aggregability regulation.

Topics: Angina Pectoris; Cardiovascular Agents; Exercise Test; Exercise Tolerance; Humans; Myocardial Ischemia; Physical Exertion; Predictive Value of Tests; Prognosis; Time Factors

Topics: Animals; Benzazepines; Cardiovascular Agents; Heart Conduction System; Heart Rate; In Vitro Techniques; Myocardial Ischemia; Rabbits; Sheep

Free radicals may cause part of the irreversible injury which occurs during myocardial infarction and reperfusion. In the present study MDL 73404, a hydrophilic, cardioselective, free radical scavenger analogue of alpha-tocopherol, was evaluated for its effects on infarct size as well as on indicators of reperfusion injury. A pentobarbitone-anaesthetised rat model of coronary artery ligation (60 min; followed by 8 days of reperfusion) was used. Intravenous infusion of MDL 73404 (3 mg/kg per h) began 10 min before occlusion until 30 min after the onset of reperfusion. MDL 73404 reduced (P < 0.02) the elevated serum levels of thiobarbituric acid reactive substances and plasma levels of creatine phosphokinase (P < 0.01). An increase in cardiac output and heart rate together with a decrease (P < 0.01) in infarct size was evident in rats that had received MDL 73404, 8 days previously. Isolated infarcted hearts obtained from rats after 8 days of reperfusion had greater (P < 0.01) + dP/dt max, -dP/dt max, left ventricular systolic pressure and coronary flow after MDL 73404 compared to saline-treated controls. Infusion of [14C]MDL 73404, during the time of occlusion resulted in a concentration of 14.5 +/- 2.2 mg eq/g in the non-ischaemic ventricular tissue and a concentration of 3.0 +/- 0.4 mg eq/g in the area at risk. After infusion for the 30 min of reperfusion, 6.4 +/- 0.2 mg eq/g was detected in the non-ischaemic ventricular tissue but only 3.1 +/- 0.5 mg eq/g in the area at risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cardiovascular Agents; Catecholamines; Coronary Circulation; Creatine Kinase; Epinephrine; Free Radical Scavengers; In Vitro Techniques; Lipid Peroxidation; Lipid Peroxides; Male; Myocardial Contraction; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Norepinephrine; Rats; Rats, Sprague-Dawley; Vitamin E

Topics: Adult; Aged; Cardiovascular Agents; Chronic Disease; Drug Therapy, Combination; Erythrocytes; Heart Failure; Hemodynamics; Humans; Male; Methylhydrazines; Middle Aged; Myocardial Ischemia