cardiovascular-agents and Ventricular-Dysfunction--Left

Historically, only patients with a left ventricular ejection fraction (LVEF) of less than or equal to 40% were considered to have heart failure (HF). However, it was later found that patients could have elevated cardiac filling pressures and the stigmata of HF signs and symptoms with normal LVEF. This subset of patients has undergone multiple taxonomical variations and is now termed heart failure with preserved ejection fraction (HFpEF) with the lower limit of LVEF assigned as roughly ≥40%-50% in clinical trials and ≥50% in HF guidelines. Patients with LVEF 41%-49% did not clearly fit these designations but bear resemblance to both heart failure with reduced ejection fraction (HFrEF) and HFpEF. This cohort was initially assigned the term HFpEF (borderline), which has also undergone several modifications and is currently termed heart failure with mildly reduced ejection fraction (HFmrEF). Earlier landmark HF trials were heavily focused on patients with HFrEF. Only in the last 2 decades has there been an increasing focus on HFpEF with emergence of key drug therapies including sodium-glucose cotransport-2 inhibitors that have shown to improve outcomes across the whole LVEF spectrum. There is yet to be a focused clinical trial to determine therapeutic modalities for HFmrEF; most of the evidence has been extrapolated from subgroup analysis mostly from HFpEF trials. In this review, we provide an overview of the historical basis of HFpEF and HFmrEF and discuss key therapeutic advances in their management.

Topics: Cardiovascular Agents; Heart Failure; Humans; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

Acute ventricular dysfunction (AVD) is a complex condition with substantial morbidity and mortality, still featuring unique therapeutic challenges. Levosimendan is a calcium sensitizer and ATP-dependent potassium channel opener that was developed as an inodilating drug for the treatment of acute heart failure and cardiogenic shock. Differently from other more widely used inotropic agents, levosimendan has some exclusive characteristics, in terms of mechanisms of action, pharmacodynamic profile, and haemodynamic effects. This may have important clinical implications. In particular, in patients with AVD or in patients with pre-existing severe ventricular impairment undergoing planned myocardial stress, the administration of levosimendan before the onset of overt symptoms or before cardiovascular therapeutic procedures may have the potential to bridge the patient through the critical phase. In this review, we will focus on the rationale, the existing experimental data, and the emerging clinical experience supporting an early, even preventive use of levosimendan in severe ventricular dysfunction, beyond its recognized indications.

Topics: Animals; Cardiovascular Agents; Humans; Recovery of Function; Simendan; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

After an episode of myocardial infarction (MI), patients remain at risk for recurrent ischemic events, heart failure (HF), and sudden death. Post-MI patients with left ventricular systolic dysfunction (LVSD) have an even greater risk of mortality and morbidity. Randomized clinical trials that included post-MI patients with LVSD have demonstrated that pharmacologic therapies aimed at preventing post-MI remodeling with neurohormonal antagonists can significantly improve short- and long-term outcomes, including death, reinfarction, and worsening HF. Recent trials have also demonstrated benefits in terms of cardiovascular event reduction with effective antithrombotic therapies and cholesterol-lowering agents in post-MI setting, especially in patients at very high risk such as those with LVSD. This paper reviews clinical trials that included post-MI patients with LVSD, with or without signs and symptoms of HF, assessing the efficacy of established and emerging pharmacological therapies.

Topics: Cardiovascular Agents; Evidence-Based Medicine; Heart Failure; Humans; Myocardial Infarction; Recovery of Function; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

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 purpose of this article is to provide an overview of revascularization in patients with coronary artery disease (CAD) and left ventricular dysfunction (LVD).. Patients with significant CAD and LVD are a high-risk patient population. They make up a minority of the cases from the largest, prospective coronary revascularization trials. The Surgical Treatment for Ischemic Heart Failure (STICH) Trial and its substudies are the most important and well cited in this field. The 10-year data from STICH showed that surgical revascularization was associated with lower all-cause mortality compared with medical therapy. Several smaller studies have confirmed that surgical revascularization carries a significant risk of short-term mortality but overall improved long-term outcomes in patients with LVD. Data from multiple observational studies further confirm that coronary artery bypass graft (CABG) is superior to percutaneous coronary revascularization for long-term survival and freedom from repeat revascularization in patients with LVD. We suggest that patients with LVD undergoing CABG should be considered for multiarterial grafting and that some patients may benefit from an off-pump procedure.. Surgical revascularization confers a long-term survival benefit in patients with significant CAD and LVD. Further studies will be needed to precisely determine the ideal candidate for surgical versus percutaneous revascularization.

Topics: Cardiovascular Agents; Coronary Artery Bypass; Coronary Artery Disease; Heart Failure; Humans; Percutaneous Coronary Intervention; Practice Guidelines as Topic; Treatment Outcome; Ventricular Dysfunction, Left

Pulmonary hypertension (PH) due to left ventricular heart failure (LV-HF) is a disabling and life-threatening disease for which there is currently no single marketed pharmacological agent approved. Despite recent advances in the pathophysiological understanding, there is as yet no prospect of cure, and the majority of patients continue to progress to right ventricular failure and die. There is, therefore an urgent unmet need to identify novel pharmacological agents that will prevent or reverse the increase in pulmonary artery pressures while enhancing cardiac performance in PH due to LV-HF. In the present article, we first focused on the Natriuretic Peptide Receptor type C (NPR-C) based therapeutic strategies aimed at lowering pulmonary artery pressure. Second, we reviewed potential NPR-C therapeutic strategies to reverse or least halt the detrimental effects of diastolic dysfunction and impaired nitic oxide signalling pathways, as well as possibilities for neurohumoral modulation.

Topics: Animals; Cardiovascular Agents; Heart Failure; Humans; Hypertension, Pulmonary; Natriuretic Peptide, C-Type; Treatment Outcome; Ventricular Dysfunction, Left

Peripartum cardiomyopathy (PPCM) is a potentially life-threatening pregnancy-associated disease that typically arises in the peripartum period. While the disease is relatively uncommon, its incidence is rising. It is a form of idiopathic dilated cardiomyopathy, defined as pregnancy-related left ventricular dysfunction, diagnosed either towards the end of pregnancy or in the months following delivery, in women without any other identifiable cause. The clinical presentation, diagnostic assessment and treatment usually mirror that of other forms of cardiomyopathy. Timing of delivery and management require a multidisciplinary approach and individualization. Subsequent pregnancies generally carry risk, but individualization is required depending on the pre-pregnancy left ventricular function. Recovery occurs in most women on standard medical therapy for heart failure with reduced ejection fraction, more frequently than in other forms of nonischemic cardiomyopathy. The purpose of this review is to summarize the current state of knowledge with regard to diagnosis, treatment and management, with a focus on long term implications.

Topics: Cardiomyopathy, Dilated; Cardiovascular Agents; Female; Humans; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Puerperal Disorders; Recovery of Function; Risk Factors; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Cardiac Catheterization; Cardiovascular Agents; Clinical Decision-Making; Echocardiography; Heart Valve Prosthesis Implantation; Heart Ventricles; Humans; Mitral Valve; Mitral Valve Insufficiency; Predictive Value of Tests; Randomized Controlled Trials as Topic; Risk Factors; Severity of Illness Index; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

A series of hemodynamic and pathological responses occur in chronic aortic regurgitation, which eventually result in myocardial fibrosis and irreversible left ventricular dysfunction. According to guidelines, valvular surgery is recommended with the development of symptoms, left ventricular systolic dysfunction, or left ventricular dilatation. The optimal timing of surgical intervention has recently been questioned with documentation of irreversible myocardial damage resulting in incomplete left ventricular recovery and adverse clinical outcomes after surgery. Recognizing the shortcomings of the guidelines, we performed a comprehensive review on the novel diagnostic methods that have been shown to improve the detection of subclinical ventricular dysfunction in chronic aortic regurgitation and to improve prediction of outcomes.

Topics: Aged; Aortic Valve Insufficiency; Asymptomatic Diseases; Cardiovascular Agents; Chronic Disease; Disease Progression; Early Diagnosis; Female; Fibrosis; Heart Valve Prosthesis Implantation; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Myocardium; Predictive Value of Tests; Recovery of Function; Time Factors; Time-to-Treatment; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

This review summarizes the current management of heart failure (HF) in patients with reduced ejection fraction and the potential role of heart rate lowering agents in select populations, as recommended in the updated guidelines. Areas covered: PubMed was searched for studies that evaluated the role of heart rate lowering or ivabradine in HF management. Expert commentary: Targeting heart rate may offer benefit when added to renin-angiotensin aldosterone antagonists, and beta-blockers. Ivabradine is a heart rate lowering agent that acts on the funny current (I

Topics: Adrenergic beta-Antagonists; Benzazepines; Cardiovascular Agents; Chronic Disease; Heart Failure; Heart Failure, Systolic; Heart Rate; Hospitalization; Humans; Ivabradine; Treatment Outcome; Ventricular Dysfunction, Left

Ivabradine is licensed as add-on therapy in patients with severe left ventricular systolic dysfunction (LVSD), normal sinus rhythm, and suboptimal heart rate (HR) control, but effects are not fully established. This study sought to assess the impact of ivabradine therapy on hemodynamic and functional outcome measures in all patients with LVSD.. MEDLINE (1996-2017), Embase (1996-2017), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews, ClinicalTrials.gov , and ISI Web of Science were searched for randomized clinical trials (RCTs) comparing standard medical therapy (SMT) plus ivabradine to SMT alone for patients with LVSD of any severity. Each trial was assessed using the Cochrane Collaborations Risk of Bias tool.. Eight RCTs with 17,823 patients were included. Add-on use of ivabradine reduced resting HR (mean difference [MD] 10.3 bpm; p < 0.001), improved ejection fraction (EF) (MD 3.6%, p < 0.001), and preserved systolic blood pressure (MD 3.4 mmHg; p = 0.09). Stratified analyses according to severity of LVSD did not influence conferred benefits on HR and EF. Small improvements were noted in exercise tolerance (standardized MD 5.9 s; p = 0.004) and peak oxygen consumption (MD 2.9 ml/kg/min; p = 0.02).. Adjunct therapy with ivabradine in patients with LVSD results in a favorable hemodynamic profile and correlates with improved functional capacity. Benefits appear to be broadly preserved irrespective of baseline EF. This was a meta-analysis of RCTs, though limited by exclusion of post hoc analyses, lack of access to patient level data, and inter-study variability in some baseline characteristics. Further, large-scale RCTs are warranted to evaluate effectiveness of ivabradine in cohorts with non-severe LVSD.

Topics: Blood Pressure; Cardiovascular Agents; Exercise Tolerance; Hemodynamics; Humans; Ivabradine; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left

Resting heart rate has long been thought to be a risk factor in cardiovascular disease and a prognostic factor in heart failure. β-Blockers were originally used in heart failure for their heart rate control abilities. However, they also have negative inotropic effects contributing to their overall benefit. The role of isolated heart rate modification is unclear in left ventricular systolic dysfunction.. Two recent studies looked at the heart rate-lowering effects of the If, or funny current inhibitor ivabradine and its potential role in heart failure therapy. At the doses chosen for the studies, ivabradine is presumed to have only effects on heart rate with no other cardiotropic effects. Thus, the cardiovascular outcome benefits are presumed to be secondary to heart rate modification.. The two recent trials showed both heart rate and cardiovascular events to be significantly lower in the ivabradine-treated group of patients with left ventricular systolic dysfunction and initial heart rate at least 70 beats/min. However, neither of these trials proved causality. Hence, the link between heart rate and improved cardiovascular outcomes still remains muddled.

Topics: Benzazepines; Cardiovascular Agents; Cyclic Nucleotide-Gated Cation Channels; Heart Failure; Heart Rate; Humans; Ivabradine; Outcome Assessment, Health Care; Ventricular Dysfunction, Left

Heart failure (HF) is a systemic disease that can be divided into HF with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF). HFpEF accounts for over 50% of all HF patients and is typically associated with high prevalence of several comorbidities, including hypertension, diabetes mellitus, pulmonary hypertension, obesity, and atrial fibrillation. Myocardial remodeling occurs both in HFrEF and HFpEF and it involves changes in cardiac structure, myocardial composition, and myocyte deformation and multiple biochemical and molecular alterations that impact heart function and its reserve capacity. Understanding the features of myocardial remodeling has become a major objective for limiting or reversing its progression, the latter known as reverse remodeling (RR). Research on HFrEF RR process is broader and has delivered effective therapeutic strategies, which have been employed for some decades. However, the RR process in HFpEF is less clear partly due to the lack of information on HFpEF pathophysiology and to the long list of failed standard HF therapeutics strategies in these patient's outcomes. Nevertheless, new proteins, protein-protein interactions, and signaling pathways are being explored as potential new targets for HFpEF remodeling and RR. Here, we review recent translational and clinical research in HFpEF myocardial remodeling to provide an overview on the most important features of RR, comparing HFpEF with HFrEF conditions.

Topics: Animals; Cardiovascular Agents; Drug Design; Heart Failure; Humans; Hypertrophy, Left Ventricular; Molecular Targeted Therapy; Myocardium; Recovery of Function; Signal Transduction; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Heart failure is the commonest cause of hospitalization and of rehospitalization This review paper is a comprehensive review of current treatment of heart failure in 2016. The target of this review is all health care professionals who treat patients with heart failure. Areas covered: This article discusses stages of heart failure, treatment of heart failure with general measures, and drug therapy with diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, aldosterone antagonists, isosorbide dinitrate plus hydralazine, digoxin, other neurohormonal antagonists, sacubitril/valsartan, calcium channel blockers, and ivabradine. This article also discusses treatment of heart failure with use of cardiac resynchronization therapy, implantable cardioverter-defibrillators, and surgical therapy, and management of end-stage heart failure. This paper was written after an extensive Medline search reviewing articles written from 1970 through May, 2016. Expert commentary: Our approach as physicians must emphasize prevention of heart failure as well as treating it. Risk factors for developing heart failure, especially hypertension, must be better controlled starting in childhood. I concur with the current heart failure treatment guidelines (Tables 1 and 2 in this paper).

Topics: Cardiovascular Agents; Defibrillators, Implantable; Heart Failure; Humans; Stroke Volume; Ventricular Dysfunction, Left

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

Congestive heart failure (CHF) is the inability of the heart to meet the metabolic demands of the body. As a disease of the advanced age with a frequency of 1-2% of the population it is rare in infancy and childhood. The incidence ranges from 2.95 (in all US children's hospitals) to 23.2 (University's Childrens Hospital Essen) on 1 000 discharges. Among the diagnostic procedures echocardiography is the primary modality of imaging. Tei-index and tissue-Doppler are more sensitive parameters for LV-dysfunction. BNP/NT-proBNP are age-dependent and can guide the long-term therapy. Treatment in childhood does not differ basically from that in adulthood, recommended by several guidelines, but data regarding the various substances - outlined in detail - are very limited. Here a big work has to be done in future!

Topics: Biomarkers; Cardiovascular Agents; Child; Child, Preschool; Chronic Disease; Cross-Sectional Studies; Echocardiography; Heart Defects, Congenital; Heart Failure; Humans; Infant; Survival Rate; Ventricular Dysfunction, Left

Heart failure (HF) is commonly described according to the severity of symptoms, using the New York Heart Association (NYHA) classification, and the assessment of ventricular function, by measuring the left ventricular ejection fraction (LVEF). It is important to acknowledge, however, that the severity of symptoms does not systematically correlate with the level of ventricular systolic dysfunction. Patients with no or only mild symptoms are still at high risk of HF-related morbidity and mortality. The objective of this review was to summarize the prevalence, characteristics, and treatment of patients with chronic HF and mild or no symptoms and to review epidemiological data from three recent registries conducted in Europe. From a clinical practice perspective, patients with a reduced ejection fraction who have only mild symptoms appear to represent a group of patients for whom the provision of adequate medical care is yet to be optimized. While prescription of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and beta-blockers appears to be consistently high, the use of mineralocorticoid receptor antagonists is more variable and does not appear to be in accordance with the latest clinical guidelines. As approximately half of patients with HF and a reduced LVEF have NYHA class II symptoms, significant reductions in morbidity and mortality could be achieved by more comprehensive treatment of this population.

Topics: Cardiovascular Agents; Disease Management; Europe; Heart Failure; Humans; Outcome Assessment, Health Care; Patient Acuity; Patient Selection; Prevalence; Prognosis; Randomized Controlled Trials as Topic; Stroke Volume; Ventricular Dysfunction, Left

Acute cardiogenic pulmonary edema and cardiogenic shock are two of the main forms of presentation of acute heart failure. Both entities are serious, with high mortality, and require early diagnosis and prompt and aggressive management. Acute pulmonary edema is due to the passage of fluid through the alveolarcapillary membrane and is usually the result of an acute cardiac episode. Correct evaluation and clinical identification of the process is essential in the management of acute pulmonary edema. The initial aim of treatment is to ensure hemodynamic stability and to correct hypoxemia. Other measures that can be used are vasodilators such as nitroglycerin, loop diuretics and, in specific instances, opioids. Cardiogenic shock is characterized by sustained hypoperfusion, pulmonary wedge pressure > 18 mmHg and a cardiac index < 2.2l/min/m(2). The process typically presents with hypotension (systolic blood pressure < 90 mmHg or a decrease in mean arterial pressure > 30 mmHg) and absent or reduced diuresis (< 0.5 ml/kg/h). The most common cause is left ventricular failure due to acute myocardial infarction. Treatment consists of general measures to reverse acidosis and hypoxemia, as well as the use of vasopressors and inotropic drugs. Early coronary revascularization has been demonstrated to improve survival in shock associated with ischaemic heart disease.

Topics: Acute Disease; Cardiovascular Agents; Combined Modality Therapy; Diagnosis, Differential; Diuresis; Heart Failure; Humans; Hypotension; Hypoxia; Myocardial Infarction; Myocardial Revascularization; Narcotics; Oxygen Inhalation Therapy; Pulmonary Edema; Respiration, Artificial; Sepsis; Shock; Shock, Cardiogenic; Sodium Potassium Chloride Symporter Inhibitors; Vasoconstrictor Agents; Vasodilator Agents; Ventricular Dysfunction, Left

Topics: Antihypertensive Agents; Aortic Valve Insufficiency; Aortic Valve Stenosis; Cardiac Catheterization; Cardiology; Cardiovascular Agents; Disease Management; Echocardiography; Evidence-Based Medicine; Exercise Test; Heart Defects, Congenital; Heart Valve Diseases; Heart Valve Prosthesis Implantation; Hemodynamics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mitral Valve Insufficiency; Mitral Valve Stenosis; Patient Care Team; Pharyngitis; Referral and Consultation; Rheumatic Fever; Secondary Prevention; Severity of Illness Index; Streptococcal Infections; United States; Vasodilator Agents; Ventricular Dysfunction, Left

Topics: Algorithms; Cardiovascular Agents; Combined Modality Therapy; Diuretics; Evidence-Based Medicine; Guideline Adherence; Heart Failure; Humans; Neurosecretory Systems; Ventricular Dysfunction, Left

Topics: Cardiac Resynchronization Therapy; Cardiovascular Agents; Combined Modality Therapy; Echocardiography, Transesophageal; Heart Failure; Heart Valve Prosthesis Implantation; Humans; Mitral Valve; Mitral Valve Insufficiency; Percutaneous Coronary Intervention; Postoperative Complications; Practice Guidelines as Topic; Prognosis; Risk Factors; Surgical Instruments; Survival Rate; Ventricular Dysfunction, Left

Topics: Algorithms; Cardiac Output, Low; Cardiac Resynchronization Therapy; Cardiovascular Agents; Defibrillators, Implantable; Echocardiography, Three-Dimensional; Echocardiography, Transesophageal; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Image Processing, Computer-Assisted; Ventricular Dysfunction, Left

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

Chronic heart failure is a common public health problem. The disease has a poor prognosis with high mortality rate and the incidence increases continuously. Prognosis of chronic systolic heart failure can be improved by several different medications as well as by special cardiac interventions based on the newly-published European and American guidelines. In case of severe systolic dysfunction, hospitalization and mortality can be reduced using angiotensin converting enzyme inhibitors, angiotensin receptor blocking drugs, beta-receptor blocking agents and aldosterone antagonists, as evidenced in multicentric studies. In selected cases different cardiac interventions, such as intracardial defibrillator and/or cardiac desynchronization device implantation can be used for supporting the failing left ventricle. In terminal stage, special devices (ventricular assist device, intra-aortic balloon pump, arteficial heart) and, finally, heart transplantation can be applied. In this paper, the authors highlight therapeutic options of chronic systolic heart failure referring to recommendations of the latest, 2012 guideline from the European Society of Cardiology.

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Cardiovascular Agents; Chronic Disease; Digitalis Glycosides; Diuretics; Heart Failure, Systolic; Heart-Assist Devices; Humans; Mineralocorticoid Receptor Antagonists; Pacemaker, Artificial; Severity of Illness Index; Thromboembolism; Vasodilator Agents; Ventricular Dysfunction, Left

published data indicate that heart rate is an independent strong predictor of cardiovascular and all-cause mortality in men and women of all ages, with and without cardiovascular disease, including atherosclerosis, ventricular arrhythmias, and left ventricular dysfunction. Ivabradine is a pure heart-rate-lowering agent with well-documented antianginal and anti-ischemic properties comparable to well-established anti-anginal agents.. this short review explores recent results with ivabradine, a new medication that lowers heart rate by selectively inhibiting the I (f) current. This review also describes future potential applications.. measurement of heart rate represents an important component of the assessment of patients with coronary artery disease and chronic heart failure, and should be viewed in the same light as other risk factors, because a high heart rate has direct detrimental effects not only on myocardial ischemia but also on the progression of atherosclerosis, ventricular arrhythmias and left ventricular function. Ivabradine has anti-ischemic and antianginal efficacy equivalent to that of β-blockers and calcium channel antagonists in the treatment of chronic stable angina pectoris. Recently ivabradine has been shown to improve cardiac outcomes in stable coronary artery disease and left ventricular systolic dysfunction in patients who have heart rates of ≥ 70 bpm and in patients with stable angina.

Topics: Angina Pectoris; Animals; Benzazepines; Cardiovascular Agents; Cardiovascular Diseases; Coronary Artery Disease; Female; Heart Rate; Humans; Ivabradine; Male; Risk Factors; Ventricular Dysfunction, Left

Diastolic heart failure, also termed as heart failure with normal or preserved ejection fraction has a high prevalence and mortality world wide. The clinical manifestation comprises typical symptoms and signs of heart failure along with normal or discretely reduced left ventricular ejection fraction. Though the etiology of diastolic heart failure is incompletely understood, functional and structural abnormalities of cardiomyocytes, the extracellular matrix, and the peripheral vasculature are assumed to contribute to the etiology of diastolic heart failure. The diagnosis requires typical symptoms and signs of heart failure, evidence of elevated natriuretic peptides and an impaired diastolic ventricular function, meanwhile left ventricular systolic function is normal or just slightly impaired. Catheter and MRI exams help to ensure the diagnosis. So far, no therapy has convincingly demonstrated a reduction of morbiditiy and mortality. Therefore, current guidelines emphasize the importance of an adequate treatment of risk factors and myocardial ischemia.

Topics: Algorithms; Blood Pressure; Cardiovascular Agents; Combined Modality Therapy; Echocardiography; Heart Failure, Diastolic; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stroke Volume; Survival Rate; Ventricular Dysfunction, Left

Twenty years ago chronic heart failure was considered a contraindication for regular physical activity. Many believed exercise to be counterproductive to recovery and perhaps harmful to chronic heart failure patients. However, in recent years numerous studies have proven the feasibility and safety of exercise training in heart failure patients. Exercise now plays a pivotal role in the treatment of systolic heart failure in addition to medical or device-related therapy. Regular exercise has been shown to increase exercise capacity and quality of life, as well as reduce symptoms and lower hospitalization rates. It also has the potential to increase left ventricular ejection fraction and reduce mortality. An individual tailored regular exercise program including endurance and resistance training is recommended for all stable heart failure patients.

Topics: Cardiovascular Agents; Combined Modality Therapy; Exercise; Heart Failure; Humans; Patient Compliance; Physical Endurance; Quality of Life; Resistance Training; Survival Rate; Ventricular Dysfunction, Left

Heart failure with preserved ejection fraction (HF-PEF) is the clinical syndrome of heart failure associated with normal or near-normal systolic function. Because inhibition of the adrenergic and renin-angiotensin-aldosterone systems has been so effective in the treatment of systolic heart failure, these same therapies have been the subject of recent clinical trials of HF-PEF. In this review, we examine the current evidence about treatment of HF-PEF, with particular emphasis on reviewing the literature for large-scale randomized clinical studies. The lack of significant benefit with neurohormonal antagonism in HF-PEF suggests that this condition might not involve neurohormonal activation as a critical pathophysiologic mechanism. Perhaps heart failure as we traditionally think of it is the wrong paradigm to pursue as we try to understand this condition of volume overload known as HF-PEF.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Biphenyl Compounds; Calcium Channel Blockers; Cardiovascular Agents; Digitalis Glycosides; Exercise; Exercise Tolerance; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertrophy, Left Ventricular; Irbesartan; Mineralocorticoid Receptor Antagonists; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Stroke Volume; Tetrazoles; Ventricular Dysfunction, Left; Verapamil

Heart failure is a frequent complication of myocardial infarction. Several factors, such as recurrent myocardial ischemia, infarct size, ventricular remodeling, stunned myocardium, mechanical complications, and hibernating myocardium influence the appearance of left ventricular systolic dysfunction after myocardial infarction. Importantly, its presence increases the risk of death by at least 3- to 4-fold. The knowledge of the mechanisms and clinical features are essential for the diagnosis and treatment of left ventricular dysfunction and heart failure after myocardial infarction. Therefore, this review will focus on the clinical implications and treatment of heart failure after myocardial infarction. © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.

Topics: Cardiovascular Agents; Heart Failure; Humans; Myocardial Infarction; Stem Cell Transplantation; Treatment Outcome; Ventricular Dysfunction, Left

Topics: Cardiac Catheterization; Cardiac Resynchronization Therapy; Cardiovascular Agents; Echocardiography; Echocardiography, Three-Dimensional; Exercise Test; Heart Valve Prosthesis Implantation; Humans; Mitral Valve; Mitral Valve Insufficiency; Ventricular Dysfunction, Left

The myocardial depressant effects of excessive ethanol consumption have long been known. Excessive alcohol intake is reported in a wide range (3-40%) of patients with idiopathic dilated cardiomyopathy; furthermore, chronic excessive alcohol consumption may lead to progressive and chronic cardiac dysfunction and can be a possible cause of dilated cardiomyopathy, referred to as alcoholic cardiomyopathy (ACM). The pathophysiological mechanisms underlying ACM are poorly understood. Excessive alcohol consumption has been associated with left-ventricular myocyte loss in some animal models but not in all studies. In addition, heavy drinking may cause myocyte dysfunction, due to abnormalities in calcium homeostasis, and cause elevated levels of norepinephrine. Increasing doses of ethanol have been associated with a negative inotropic effect on myocytes in animal experiments. In this review, we evaluate the epidemiology, current pathophysiological mechanisms and possible role of factors that influence ACM and discuss its clinical presentation, prognosis and treatment.

Topics: Alcohol Drinking; Animals; Cardiomyopathy, Alcoholic; Cardiovascular Agents; Disease Progression; Female; Heart Failure; Humans; Male; Myocardium; Risk Factors; Sex Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Cardiovascular magnetic imaging is a noninvasive, three dimensional tomographic technique that allows for a detailed morphology of the cardiac chambers, the accurate quantification of right ventricle volumes, myocardial mass, and transvalvular flow. It can also determine whether right ventricular diastolic function is impaired through pulmonary hypertension. The aim of this article is to review the main kinetic, morphological and functional changes of the right ventricle that can occur in patients affected by pulmonary arterial hypertension (PAH) and to assess how the MRI findings can influence the prognosis, and guide the decision-making strategy. In those cases in which MRI shows a significant cardiac diastolic dysfunction, the prognosis is predictive of pharmacological treatment failure, and mortality. This leaves double lung-heart transplantation as the only therapeutic option. The coexistence of PAH and left ventricle impairment causes worse right ventricle function, leads to a poor prognosis, and may change the therapeutic strategies (for example, PAH associated with left ventricle dysfunction may require a double lung-heart transplant).

Topics: Adult; Blood Pressure; Cardiovascular Agents; Contrast Media; Diagnosis, Differential; Female; Heart-Lung Transplantation; Humans; Hypertension, Pulmonary; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Predictive Value of Tests; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right; Ventricular Function, Right

Cancer treatment has improved extraordinarily in recent years. The development of targeted therapies has widened the cardiotoxic spectrum of antineoplastic drugs. Optimum management of cardiovascular disease before and during antineoplastic treatment is essential to reduce morbidity and mortality in cancer patients. This article reviews the incidence and characteristics of cardiotoxic effects of antineoplastic drugs with special focus on the pathophysiological mechanisms. It also emphasizes the importance of early detection and correction of cardiovascular risk factors and the relevance of close cardiac monitoring during antineoplastic treatment in order to reduce cardiotoxicity.

Topics: Antineoplastic Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Heart Diseases; Humans; Incidence; Ischemia; Molecular Targeted Therapy; Neoplasms; Ventricular Dysfunction, Left

Primary percutaneous coronary intervention (PCI) decreases myocardial damage and reduces the occurrence of mechanical complications and acute heart failure in patients with ST elevation myocardial infarction (STEMI). Nevertheless, left ventricular (LV) dysfunction remains the leading cause of in-hospital mortality in all subsets of patients and particularly for those in whom primary PCI fails to reopen the infarct-related artery. The clinical scenarios of acute LV failure are heart failure and cardiogenic shock, both conditions being associated with extremely poor outcomes. It has been estimated that LV failure accounts for >75% of the cases of shock complicating acute STEMI. As compared to similar situations, the decision-making process in these patients can potentially benefit from the known coronary anatomy and, in many instances, from the immediate implantation of an intraaortic balloon pump at the time of PCI in selected groups of patients. A thorough clinical and instrumental evaluation is mandatory to discriminate patients who will likely recover (either spontaneously or with further conventional procedures) from those who have irreversible myocardial injury and should be screened for LV assist devices and/or emergent heart transplantation. In this review, we provide a practical diagnostic and therapeutic algorithm that may be helpful for the clinical management of patients with acute LV failure after primary PCI.

Topics: Acute Disease; Algorithms; Angioplasty, Balloon, Coronary; Cardiac Surgical Procedures; Cardiovascular Agents; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Intra-Aortic Balloon Pumping; Myocardial Infarction; Prognosis; Time Factors; Ventricular Dysfunction, Left

Diastolic heart failure (HF) is also referred to as HF with preserved left ventricular systolic function. The distinction between systolic and diastolic HFs is a pathophysiological one and isolated forms of left ventricular dysfunction are rarely observed. In diastolic HF left ventricular systolic function is normal or only slightly impaired, and the typical manifestations of HF result from increased filling pressure caused by impaired relaxation and compliance of the left ventricle. The predisposing factors for diastolic dysfunction include elderly age, female sex, obesity, coronary artery disease, hypertension and diabetes mellitus. Treatment of diastolic HF is aimed to stop the progression of the disease, relieve its symptoms, eliminate exacerbations and reduce the mortality. The management should include antihypertensive treatment, maintenance of the sinus rhythm, prevention of tachycardia, venous pressure reduction, prevention of myocardial ischemia and prevention of diabetes mellitus. The European Society of Cardiology specifies the type of therapy in diastolic HF based on: angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, non-dihydropyridine calcium channel blockers, diuretics. In order to improve the currently poor prognosis in this group of patients the treatment of diastolic HF must be optimised.

Topics: Cardiovascular Agents; Diastole; Drug Therapy, Combination; Heart Failure, Diastolic; Humans; Practice Guidelines as Topic; Stroke Volume; Systole; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Chronic stable angina pectoris (CSAP) usually occurs in patients with coronary artery disease (CAD) that affects one or more large epicardial arteries. It results when myocardial perfusion is insufficient to meet cardiac metabolic demand. Elevated heart rate (HR) is an important factor in the development of myocardial ischemia and angina pectoris. The pharmacologic agents most commonly administered in the treatment of CSAP are beta-blockers and calcium channel blockers (CCBs). However, the use of beta-blockers is limited by poor compliance related to contraindications and comorbidities, especially in elderly patients. Ivabradine is a new selective HR-lowering agent that selectively inhibits the pacemaker current I (f) in the sinus atrial node. In several randomized controlled trials, ivabradine 5-10 mg twice daily has demonstrated equivalent anti-ischemic and anti-anginal activity to beta-blockers and CCBs, with a good safety and tolerability profile. Although ivabradine has been shown not to improve cardiac outcomes in patients with stable CAD and left ventricular systolic dysfunction, it may be used to reduce the incidence of CAD outcomes in a subgroup of patients with HR > or =70 bpm. The aim of this short review is to summarize the use of ivabradine in the treatment of CSAP, and its potential utility in atherosclerosis, primitive and dilatative cardiomyopathy, and arrhythmias, such as postural tachycardia syndrome and inappropriate sinus tachycardia, where exclusive lowering of elevated HR may prove beneficial.

Topics: Adrenergic beta-Antagonists; Angina Pectoris; Benzazepines; Calcium Channel Blockers; Cardiovascular Agents; Coronary Artery Disease; Heart Failure; Heart Rate; Heart Transplantation; Humans; Ivabradine; Nitrates; Randomized Controlled Trials as Topic; Ventricular Dysfunction, Left

Cardiotoxicity is a rare but serious complication of 5-fluorouracil therapy. Coronary vasospasm and, less frequently, acute myocarditis have been identified as underlying mechanisms. We report a case of severe toxicity in a relatively young and fit male patient being treated for metastatic colonic adenocarcinoma displaying characteristics that cannot be explained by either mechanism alone.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Arrhythmias, Cardiac; Cardiomyopathy, Dilated; Cardiovascular Agents; Colonic Neoplasms; Coronary Vasospasm; Fluorouracil; Heart Diseases; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Myocarditis; Organoplatinum Compounds; Oxaliplatin; Treatment Outcome; Ventricular Dysfunction, Left

Fifty years after its discovery, aldosterone continues to stimulate interest as a therapeutic target. Early studies focused on aldosterone's actions on hypertension, the kidney, and electrolyte handling. More recently, its actions on the heart and cardiovascular system have become more apparent. Aldosterone causes cardiac fibrosis and remodeling, and stimulates neurohormonal systems that adversely affect the cardiovascular system. Aldosterone antagonism attenuates these negative effects. Clinical studies have applied this science and demonstrated improved morbidity and mortality with aldosterone blockade, specifically in patients with chronic heart failure and patients who are postmyocardial infarction and with depressed left ventricular function. This article will address the pathophysiology of aldosterone in cardiac fibrosis and remodeling, review the current clinical trial data, and explore the application of aldosterone blockade in an expanded heart failure population. The Randomized Aldactone Evaluation Study showed that the aldosterone antagonist spironolactone reduced mortality when compared to placebo in patients with chronic advanced heart failure. Similarly, the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study demonstrated a significant reduction in mortality and hospitalizations for patients randomized to the aldosterone antagonist eplerenone. A more provocative question is whether aldosterone antagonism will afford the same protection in patient populations with heart failure and preserved left ventricular function. Clinical trials are underway, and results are eagerly awaited.

Topics: Aldosterone; Cardiovascular Agents; Drug Therapy, Combination; Eplerenone; Fibrosis; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Myocardium; Spironolactone; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Remodeling

Trandolapril is a well known angiotensin converting enzyme (ACE) inhibitor with many cardiovascular (CV) indications. The objectives of this article are to review the pharmacokinetics and pharmacodynamics properties of trandolapril and to focus on its clinical relevance in cardiovascular medicine. Various populations have been studied in large clinical trials including patients with congestive heart failure (CHF) after an acute myocardial infarction (AMI), diabetics, patients with hypertension (HTN), stable coronary artery disease (CAD) and prevention of proteinuria. Long-term treatment with trandolapril in patients with reduced left ventricular function soon after AMI significantly reduced the risk of overall mortality, mortality from CV causes, sudden death, and the development of severe CHF. Treatment with trandolapril after AMI complicated by left ventricular dysfunction appears to be of considerable importance in patients with diabetes mellitus by saving lives and substantially reducing the risk of progression to severe CHF as well. Moreover, trandolapril reduces progression to proteinuria in high-risk patients. Some of the advantages of trandolapril over other ACE inhibitors are the wide spectrum of patient populations studied, the well established dosage and its proven trough-to-peak effect ratios permitting a safe once-a-day administration.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Cardiovascular Diseases; Coronary Artery Disease; Diabetes Complications; Drug Administration Schedule; Heart Failure; Humans; Hypertension; Indoles; Myocardial Infarction; Proteinuria; Treatment Outcome; Ventricular Dysfunction, Left

Diuretics are tools of considerable therapeutic importance. First, they effectively reduce blood pressure, while at the same time decreasing the morbidity and mortality associated with hypertension. Diuretics are currently recommended as first-line therapy for the treatment of hypertension. In addition, they remain an important component of heart failure therapy, in that they improve the symptoms of congestion, which typify the more advanced stages of heart failure. This article reviews the mode of action of the various diuretic classes and the physiologic adaptations that follow; sets up the basis for their use in the treatment of volume-retaining states, particularly as applies to the elderly; and reviews diuretic-related side effects that are normally encountered.

Topics: Aged; Cardiovascular Agents; Clinical Trials as Topic; Diuretics; Heart Failure; Humans; Ventricular Dysfunction, Left

Recent studies have evidenced that alterations of cardiac metabolism can be present in several cardiac syndromes. In heart failure, wasting of subcutaneous fat and skeletal muscle is relatively common and suggests an increased utilisation of non-carbohydrate substrates for energy production. In fact, fasting blood ketone bodies as well as fat oxidation during exercise have been shown to be increased in patients with heart failure. This metabolic shift determines a reduction of myocardial oxygen consumption efficiency. A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilisation by the heart. To date, the most effective metabolic treatments include several pharmacological agents that directly inhibit fatty acid oxidation. Clinical studies have shown that these agents can substantially increase the ischaemic threshold in patients with effort angina. However, the results of current research is also supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and towards glucose metabolism could be an effective adjunctive treatment in patients with heart failure, in terms of left ventricular function and glucose metabolism improvement. In fact, these agents have also been shown to improve overall glucose metabolism in diabetic patients with left ventricular dysfunction. In this paper, the recent literature on the beneficial therapeutic effects of modulation of cardiac metabolic substrates utilisation in patients with heart failure is reviewed and discussed.

Topics: Blood Glucose; Cardiovascular Agents; Endothelium, Vascular; Fatty Acids, Nonesterified; Heart Failure; Humans; Myocardium; Ventricular Dysfunction, Left

As for other critically ill diseases, two key factors may markedly improved morbidity and mortality of acute heart failure syndromes (AHFS): early initiation of treatment and tailored therapy. Early initiation aims to stop the negative cascade of heart dysfunction. Tailored therapy should be based on the level of systolic blood pressure at admission and fluid retention. Indeed, EFICA and OPTIMIZE-HF showed that patients with high systolic blood pressure have a left ventricular systolic function that is likely preserved and those with low systolic blood pressure have a lower left ventricular ejection fraction and frequent signs of organ's hypoperfusion. Among the proposed treatments, non-invasive ventilation is the only treatment that was consistently proven to be beneficial on morbidity and mortality in almost all types of AHFS. Concerning pharmacological agents, actions should be taken to increase the use of vasodilators and reduce the use of diuretics.

Topics: Acute Disease; Algorithms; Cardiotonic Agents; Cardiovascular Agents; Clinical Trials as Topic; Continuous Positive Airway Pressure; Diuretics; Heart Failure; Humans; Stroke Volume; Syndrome; Systole; Treatment Outcome; Vasoconstrictor Agents; Vasodilator Agents; Ventricular Dysfunction, Left

Implantable devices have become a readily available option for patients with heart failure. Not only do these patients develop bradycardia and ventricular tachycardia, but their ventricular dysfunction can often improve with cardiac resynchronization therapy. However, this is a complex and rapidly developing clinical science for which the physician chooses techniques and selects patients on the basis of the results of clinical trials, clinical experience, and rapidly evolving tools. The results depend on the interplay of these complex variables. Placement of the left ventricular lead has forced the device physician to develop new skills and/or interdisciplinary relationships with physicians with vascular intervention, imaging, and surgical skills. Familiarity with the cardiac venous anatomy, occlusive venography, venoplasty, guide wire tools, guiding catheters, stenting, and new intracardiac visualization and magnetic intracardiac lead positioning tools are examples of just a few of the novel skills that are useful in the delivery of cardiac resynchronization therapy. Beyond implantation, these patients and devices require specialized follow-up with continued medical therapy and echo-guided adjustments of device programming. Finally, there are ongoing controversies and many as yet unanswered questions that are the subject of ongoing and planned clinical trials.

Topics: Atrial Fibrillation; Bundle-Branch Block; Cardiac Catheterization; Cardiovascular Agents; Catheterization; Combined Modality Therapy; Defibrillators, Implantable; Electric Countershock; Electrophysiologic Techniques, Cardiac; Endoscopy; Follow-Up Studies; Heart Conduction System; Heart Failure; Heart Function Tests; Humans; Magnetics; Multicenter Studies as Topic; Pacemaker, Artificial; Phlebography; Phrenic Nerve; Randomized Controlled Trials as Topic; Treatment Outcome; Ventricular Dysfunction, Left

Natriuretic peptides, in particular, brain or B-type, are useful for the assessment of patients presenting with dyspnea to the medical office or emergency department. Levels of natriuretic peptides are useful for assessing prognosis of heart failure or coronary syndrome patients. Less is known about serial peptide measurements for guiding treatment strategies in heart failure. The authors review the uses, pitfalls, and practical points for using natriuretic peptides clinically.

Topics: Biomarkers; Cardiac Output, Low; Cardiovascular Agents; Drug Monitoring; Female; Humans; Male; Natriuretic Peptide, Brain; Sensitivity and Specificity; Sex Factors; Ventricular Dysfunction, Left

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: Aged; Blood Urea Nitrogen; Cardiac Volume; Cardiovascular Agents; Creatinine; Electrolytes; Evidence-Based Medicine; Frail Elderly; Heart Failure; Humans; Medical History Taking; Physical Examination; Process Assessment, Health Care; Quality Indicators, Health Care; Ventricular Dysfunction, Left

Maintaining adequate cardiac output in postoperative cardiac surgery patients is a complex and challenging feat for health care teams. Alterations in preload, afterload, contractility, heart rate, and rhythm can be devastating to these patients and lead to lethal consequences. An array of pharmacologic therapies is available in the critical care setting to help prevent and treat such complications and ensure satisfactory cardiac performance.

Topics: Arrhythmias, Cardiac; Cardiac Output, Low; Cardiac Surgical Procedures; Cardiovascular Agents; Humans; Postoperative Care; Ventricular Dysfunction, Left

The possibility of modifying cardiac metabolism by switching the fuel used by the myocardium could become increasingly important. Inhibitors of free fatty acid (FFA) oxidation could have an important role in therapeutic strategy for patients with heart failure, and shifting the energy substrate preference away from FFA metabolism and toward glucose metabolism may be an effective adjunctive treatment. Additionally, abnormalities of glucose homeostasis in patients with heart failure contribute to the progression of the primary disease. If not adequately treated, these abnormalities can contribute to the occurrence of complications, including severe left ventricular dysfunction. Apart from meticulous metabolic control of frank diabetes, special attention should be paid to insulin resistance, a distinct clinical entity. The observed combined beneficial effects of FFA inhibitors on left ventricular function and glucose metabolism represent an additional advantage of these drugs, especially when abnormalities of myocardial and glucose metabolism coexist.

Topics: Blood Glucose; Cardiovascular Agents; Endothelium, Vascular; Fatty Acids, Nonesterified; Heart Failure; Humans; Ventricular Dysfunction, Left

Diastolic heart failure occurs when signs and symptoms of heart failure are present but left ventricular systolic function is preserved (i.e., ejection fraction greater than 45 percent). The incidence of diastolic heart failure increases with age; therefore, 50 percent of older patients with heart failure may have isolated diastolic dysfunction. With early diagnosis and proper management the prognosis of diastolic dysfunction is more favorable than that of systolic dysfunction. Distinguishing diastolic from systolic heart failure is essential because the optimal therapy for one may aggravate the other. Although diastolic heart failure is clinically and radiographically indistinguishable from systolic heart failure, normal ejection fraction and abnormal diastolic function in the presence of symptoms and signs of heart failure confirm diastolic heart failure. The pharmacologic therapies of choice for diastolic heart failure are angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, diuretics, and beta blockers.

Topics: Cardiovascular Agents; Clinical Trials as Topic; Diagnosis, Differential; Diastole; Heart Failure; Humans; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Agents; Clinical Trials as Topic; Coronary Disease; Defibrillators, Implantable; Diabetes Complications; Disease Progression; Female; Follow-Up Studies; Health Surveys; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Mass Screening; Middle Aged; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Pacemaker, Artificial; Practice Guidelines as Topic; Prevalence; Severity of Illness Index; Stroke Volume; Systole; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Remodeling

Since 1988 with the discovery of B-type natriuretic peptide (BNP), many reports have confirmed the elevation of plasma BNP in symptomatic heart failure and confirmed that plasma levels are an independent predictor of death and cardiovascular events in both acute and chronic heart failure.. A more slender evidence base attests that knowledge of plasma BNP levels can be used to produce clinical benefit. One randomized controlled trial demonstrated that measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP) can be used to improve diagnostic accuracy in patients with heart failure in the community. A second study demonstrated that the provision of plasma BNP data improves the speed of diagnosis and reduces the rates of hospital admission and length of hospital stay (while reducing the costs of care) in patients with heart failure who are seen the emergency department with acute dyspnea. Finally, a randomized controlled pilot study demonstrated that serial measurements of NT-proBNP can be used to more effectively optimize heart failure pharmacotherapy with a concomitant improvement in outcome.. The large body of observational data, coupled with this small but promising evidence base from controlled trials (which attests to beneficial effects on clinical outcomes) encourages an optimistic outlook for the further implementation of plasma BNP and/or NT-proBNP in the diagnosis and treatment of acute and chronic heart failure.

Topics: Cardiovascular Agents; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Randomized Controlled Trials as Topic; Treatment Outcome; Ventricular Dysfunction, Left

The main goal of current antihypertensive therapy is to achieve a lowering of intra-arterial pressure by various mechanisms. A plethora of data suggests that this reduces cardiovascular morbidity and mortality due to stroke, heart failure and to a lesser extent, ischemic heart disease. Early cardiac manifestations of chronic hypertension, left ventricular hypertrophy (LVH) and diastolic dysfunction (CHF-D) confer additional risk of cardiovascular morbidity and mortality in patients with hypertension. Regression of left ventricular (LV) mass with antihypertensive therapy is associated with improved diastolic function and overall reduction in cardiovascular events, and this benefit may be independent of actual lowering of arterial pressure. Antihypertensive therapy should therefore be geared to both lower arterial blood pressure and specifically reverse pathophysiologic processes that promote LVH and CHF-D. Emerging therapies accomplish this without specifically affecting blood pressure. Therefore, future treatments for hypertension may require a combination of drugs performing complimentary tasks in lowering arterial pressure and reversing maladaptive physiologic and genetic processes causing hypertensive heart disease. This review summarizes the current and emerging approaches to the treatment of individuals with hypertensive heart disease.

Topics: Antihypertensive Agents; Cardiac Output, Low; Cardiovascular Agents; Heart Failure; Humans; Hypertension; Hypertrophy, Left Ventricular; Ventricular Dysfunction, Left

The results of recent studies provide the evidence that extract of hawthorn (Crataegus sp.) may provide benefits in left ventricular systolic dysfunction. The authors present a number of in vitro and in vivo studies in which the influence of this herbal drug on contractility of impaired myocardium has been proved. This kind of supplementary therapy was well tolerated and no interactions with the other compounds for heart failure were reported.

Topics: Cardiovascular Agents; Crataegus; Humans; Phytotherapy; Plant Extracts; Proanthocyanidins; Ventricular Dysfunction, Left

The pharmacologic management of the patient post myocardial infarction (MI) aims to achieve several goals. Chief among these is to prevent subsequent events, which include death, reinfarction, and rehospitalization. Secondary goals include preventing arrhythmias, minimizing left ventricular (LV) remodeling, and preventing progression to heart failure. This review describes practical algorithms for use in the pharmacologic management of the patient post MI based on American Heart Association/American College of Cardiology guidelines. The intensity of drug treatment is determined guided by the degree of LV dysfunction and the presence or absence of ischemia and arrhythmic risk markers. All patients post MI require an angiotensin-converting enzyme (ACE) inhibitor and antiplatelet therapy, usually with aspirin. In individuals who cannot tolerate an ACE inhibitor, an angiotensin receptor blocker (ARB) is an adequate substitute. Numerous studies document the efficacy of ACE inhibitors, which decrease mortality and the risk of heart failure and stroke. Aldosterone blockade is recommended long-term for patients post MI with an LV ejection fraction < or = 40% and either symptomatic heart failure or diabetes. Use of a beta blocker is an important addition to most post-MI drug regimens. Beta blockers decrease mortality and are especially effective in patients with impaired LV function. Among the beta blockers, carvedilol, which also has alpha-adrenergic receptor blocking activity, was found to decrease mortality significantly in patients with low ejection fractions and heart failure. Another drug therapy of value in post-MI treatment is use of calcium-channel blockers. These are restricted to patients with conserved LV function in whom congestion is absent and in whom beta blockers are contraindicated. Current guidelines also recommend that patients post MI with elevated cholesterol levels should be prescribed lipid therapy with a statin at hospital discharge.

Topics: Adrenergic beta-Antagonists; Algorithms; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Agents; Fish Oils; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Platelet Aggregation Inhibitors; Severity of Illness Index; Ventricular Dysfunction, Left; Ventricular Remodeling

Patients with left ventricular dysfunction (LVD) are at increased risk for dying suddenly of cardiac causes. The most common causes of LVD are coronary artery disease (CAD) and myocardial infarction (MI). Aggressive intervention following MI is essential for minimizing the myocardial damage that leads to LVD and the subsequent risk for heart failure and sudden cardiac death. This article describes practical algorithms for managing the patient post MI to minimize such risks. The degree of LVD is a key factor for determining clinical management strategies in the patient post MI. Risk factor reduction and selective neurohormonal blockade, especially with angiotensin-converting enzyme inhibitors, are usually recommended in the presence or absence of LVD, along with early use of a beta blocker. In patients with LVD, more aggressive intervention includes extended use of a beta blocker. In cases of LVD progressed to heart failure, the mixed beta and alpha blocker carvedilol has improved outcomes significantly. In clinical trials, carvedilol has been demonstrated to have antiarrhythmic activity, a property that offers protection against sudden arrhythmic death in high-risk patients with LVD. Addition of an aldosterone antagonist is also advised in patients with heart failure. In selected patients with reduced ejection fractions, use of surgical/catheter treatment and device therapy offers further benefits.

Topics: Adrenergic beta-Antagonists; Algorithms; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Cardiovascular Agents; Cardiovascular Surgical Procedures; Defibrillators, Implantable; Humans; Myocardial Infarction; Risk Factors; Risk Reduction Behavior; Ventricular Dysfunction, Left

Topics: Aged; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiovascular Agents; Diabetic Nephropathies; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Female; Heart Failure; Humans; Hypertension; Kidney Diseases; Male; Middle Aged; Myocardial Infarction; Proteinuria; Rats; Renin-Angiotensin System; Ventricular Dysfunction, Left

Diastolic heart failure (heart failure with preserved systolic function) causes 30% to 50% of all cases of heart failure, and its prognosis is almost as ominous as that of systolic heart failure. Currently, it is diagnosed when clinical criteria for heart failure are present and left ventricular ejection fraction is preserved (higher than 40% to 50%). However, determinations of brain natriuretic peptides may play an important role in the future. Because we have no evidence from clinical trials, with the exception of the slight benefit obtained with candesartan in reducing hospitalizations in the CHARM Study, treatment of diastolic heart failure is based on the identification and treatment of the causal factor (hypertension, coronary heart disease), control of heart rate, and relief of fluid congestion. Thus, combined therapy with low-dose diuretics, antihypertensive drugs for bradycardia (beta blockers, calcium antagonists) and angiotensin antagonists seems now to be the best therapeutic strategy.

Topics: Cardiovascular Agents; Clinical Trials as Topic; Diastole; Heart Failure; Humans; Prognosis; Ventricular Dysfunction, Left

Coronary artery disease is a major contributor to the progression of left ventricular systolic dysfunction and heart failure (HF). Recognizing that coronary artery disease is a leading cause of HF in the United States is critical to reducing mortality resulting from this condition. Although some patients may be candidates for mechanical revascularization to improve left ventricular function, all patients are candidates for aggressive secondary prevention strategies. This review discusses the prevalence of coronary artery disease, prognostic significance and pathophysiology, risk factor modifications, pharmacologic treatments, and the role of revascularization.

Topics: Age Distribution; Cardiovascular Agents; Chronic Disease; Coronary Artery Disease; Death, Sudden, Cardiac; Diabetes Complications; Disease Progression; Heart Failure; Humans; Hyperlipidemias; Hypertension; Morbidity; Myocardial Revascularization; Obesity; Practice Guidelines as Topic; Prevalence; Primary Prevention; Prognosis; Risk Factors; Risk Reduction Behavior; Smoking; United States; Ventricular Dysfunction, Left; Ventricular Remodeling

Traditionally, clinicians have viewed heart failure either as a problem of excessive salt and water retention caused by abnormalities of renal blood flow, or as a hemodynamic problem associated with a reduced cardiac output and excessive peripheral vasoconstriction. Recently, clinicians have begun to adopt a neurohormonal model in which heart failure progresses because of the toxic effects of endogenous biological systems that become activated in heart failure. We review the rationale for existing heart failure therapies and discuss the reasoning behind the development of some emerging therapies.

Topics: Animals; Cardiovascular Agents; Cytokines; Heart Failure; Humans; Neurotransmitter Agents; Ventricular Dysfunction, Left; Ventricular Remodeling

We sought to determine the effect of angiotensin receptor blockers (ARBs) on mortality and hospitalization in patients with heart failure (HF).. There is uncertainty regarding the efficacy of ARBs as substitute or adjunctive therapy to angiotensin-converting enzyme inhibitors (ACEIs) in the treatment of HF.. We conducted a meta-analysis of all randomized controlled trials that compared ARBs with either placebo or ACEIs in patients with symptomatic HF. The pooled outcomes were all-cause mortality and hospitalization for HF.. Seventeen trials involving 12,469 patients were included. Overall, ARBs were not superior to controls in the pooled rates of death (odds ratio: 0.96; 95% confidence interval: 0.75 to 1.23) or hospitalization (0.86; 0.69 to 1.06). Stratified analysis, however, showed a non-significant trend in benefit of ARBs over placebo in reducing mortality (0.68; 0.38 to 1.22) and hospitalization (0.67; 0.29 to 1.51) when given in the absence of background ACEI therapy. When compared directly with ACEIs, ARBs were not superior in reducing either mortality (1.09; 0.92 to 1.29) or hospitalization (0.95; 0.80 to 1.13). In contrast, the combination therapy of ARBs and ACEIs was superior to ACEIs alone in reducing hospitalization (0.74; 0.64 to 0.86) but not mortality (1.04; 0.91 to 1.20).. This meta-analysis cannot confirm that ARBs are superior in reducing all-cause mortality or HF hospitalization in patients with symptomatic HF, particularly when compared with ACEIs. However, the use of ARBs as monotherapy in the absence of ACEIs or as combination therapy with ACEIs appears promising.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Heart Failure; Humans; Randomized Controlled Trials as Topic; Risk; Survival Analysis; Treatment Outcome; Ventricular Dysfunction, Left

Topics: Atrial Natriuretic Factor; Cardiovascular Agents; Heart Failure; Humans; Models, Cardiovascular; Renin-Angiotensin System; Stroke Volume; Sympatholytics; Ventricular Dysfunction, Left; Ventricular Remodeling

Topics: Algorithms; Cardiac Pacing, Artificial; Cardiovascular Agents; Clinical Trials as Topic; Coronary Disease; Cytokines; Defibrillators, Implantable; Enzyme Inhibitors; Exercise; Heart Failure; Humans; Matrix Metalloproteinase Inhibitors; Ventricular Dysfunction, Left

Although the first non-imaging nuclear probe for clinical application was already available 25 years ago, this technique is still underused for the assessment of ventricular function. Over the years substantial technological progress rendered nuclear probes more accurate and easier to use, and so far the applicability of these devices has been evaluated in several experimental and clinical contexts. Bedside devices can be used in the evaluation of hemodynamically unstable patients and of drug therapy. In patients with several heart diseases, particularly with ischemic cardiomyopathy, accurate information on the changes in ventricular function occurring during routine activities, as well as during structured activities, can be provided using the ambulatory probes. This review will focus on the development and clinical application of these diagnostic tools.

Topics: Cardiovascular Agents; Heart; Heart Function Tests; Humans; Monitoring, Ambulatory; Monitoring, Physiologic; Point-of-Care Systems; Radionuclide Ventriculography; Ventricular Dysfunction, Left; Ventricular Function, Left

Heart failure is a changing paradigm. The hemodynamic model, which served our needs well from the 1950s through the early 1980s, has now been largely abandoned, except for the management of decompensated patients in the hospital. The pathophysiology is exceedingly complex and involves structural changes, such as loss of myofilaments, apoptosis and disorganization of the cytoskeleton, as well as disturbances in Ca(2+) homeostasis, alteration in receptor density, signal transduction, and collagen synthesis. A more contemporary working hypothesis is that heart failure is a progressive disorder of left ventricular remodeling, usually resulting from an index event, that culminates in a clinical syndrome characterized by impaired cardiac function and circulatory congestion. This change in the framework of our understanding of the pathophysiology of heart failure is predicated on the results of numerous clinical trials conducted during the past 20 years. New therapies are now evolving that are designed to inhibit neuroendocrine and cytokine activation, whereas drugs specifically designed to heighten cardiac contractility and "unload" the left ventricle have proven to be unhelpful in long-term management of patients with chronic heart failure. However, the hemodynamic model is still relevant for patients in the hospital with decompensated heart failure, where positive inotropic drugs and vasodilators are still widely used. The modern treatment of chronic heart failure is now largely based on the neurohormonal hypothesis, which states that neuroendocrine activation is important in the progression of heart failure and that inhibition of neurohormones is likely to have long-term benefit with regard to morbidity and mortality. Thus, the evolution of treatment for chronic heart failure as a result of clinical trials has provided much enlightenment for our understanding of the fundamental biology of the disorder, a reversal of the usual flow of information from basic science to clinical investigation.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiotonic Agents; Cardiovascular Agents; Chronic Disease; Diuretics; Heart Conduction System; Heart Failure; Hormones; Humans; Hypertrophy, Left Ventricular; Myocardial Contraction; Myocardium; Vasodilator Agents; Ventricular Dysfunction, Left; Ventricular Remodeling

Heart failure imposes a major burden on society. Primary care physicians, who care for 70% of all heart-failure patients, have opportunities to reduce the economic and mortality impact of this disease by improved outpatient management. Management tasks for these patients are discussed. Successful completion of these tasks will lead to an improvement in functional capacity, fewer hospitalizations, and longer lives for heart-failure patients.

Topics: Adult; Aged; Cardiovascular Agents; Female; Heart Failure; Humans; Male; Middle Aged; Primary Health Care; Referral and Consultation; Self Care; Ventricular Dysfunction, Left

Diastolic left ventricular function is altered substantially with advancing age in healthy persons, and diastolic dysfunction impacts most cardiovascular disorders in the elderly. Older, healthy persons have a delayed relaxation Doppler filling pattern and their early deceleration time is similar to, or modestly lengthened, compared with younger, healthy persons. Two abnormal Doppler filling patterns, the pseudo-normal and the restricted, are discerned more easily, and are more specific in the elderly than the young, because they are the opposite (reverse) of the normal elderly pattern. Most heart failure in the elderly occurs in the presence of preserved systolic function (presumed diastolic heart failure). Elderly patients with diastolic heart failure tend to be women with hypertrophied, hyperdynamic left ventricles, and chronic hypertension. Prognosis may be somewhat better than in systolic heart failure, but the difference diminishes when adjusted for gender and in the very elderly. The pathophysiology of this disorder is not well characterized, diagnostic criteria have not been standardized, and there are no large, multicenter, randomized trials to guide therapy. Further research in this area should be a high priority.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Diastole; Female; Hemodynamics; Humans; Male; Randomized Controlled Trials as Topic; Survival Rate; Ventricular Dysfunction, Left

Diabetes mellitus as a disease of epidemiological impact leads to diabetic cardiopathy by modulation of myocardial, vascular and metabolic components. This includes the development of a coronary microangiopathy and a decrease of diastolic and systolic function of the left ventricle as well as the development of an autonomic diabetic neuropathy. Patients with diabetes show an increased mortality concerning cardiovascular events. They more often suffer from myocardial infarction as non-diabetics mostly with a more serious course. Moreover, the post-infarction course is affected with a worse prognosis as in non-diabetics. For diagnosis of cardial involvement in diabetes electrocardiographic and echocardiographic procedures are of use. Special tests of the autonomic function complete the diagnostic ensemble. An early therapy with ACE-inhibitors and beta blocking agents as well as a strong diabetes therapy, in particular with insulin, can influence the mortality favorably. Moreover, the diagnosis and therapy of additional cardiovascular risk factors (arterial hypertension, dyslipidemia) are very important, because these are correlated with a for diabetic patients markedly increased risk of mortality. The clinical relevance of the term diabetic cardiopathy is justified by the 6 factors: macroangiopathy, microangiopathy, disturbances of the myocardial metabolism, myocardial fibrosis, autonomic diabetic neuropathy and disturbances of the coagulability. Diagnostic and therapeutic goals are discussed.

Topics: Arteriosclerosis; Cardiovascular Agents; Coronary Disease; Diabetes Complications; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Neuropathies; Diagnosis, Differential; Humans; Lipids; Myocardial Infarction; Risk Factors; Ventricular Dysfunction, Left

Diastolic dysfunction is the underlying problem in one third of patients with heart failure, but it is still not well understood. Carefully excluding other causes of heart failure and recognizing indicators of diastolic dysfunction on invasive and noninvasive tests are important in establishing the diagnosis and in guiding therapy. Left ventricular relaxation and stiffness and left atrial function are the most important factors acting together to maintain adequate cardiac output under normal filling pressure. Echocardiography is the most important tool for the diagnosis of diastolic heart dysfunction. It is portable, safe, and excludes other causes of heart failure, such as valvular disease. Diuretics can be used to reduce volume overload, but caution is advised, as aggressive diuresis decreases stroke volume more in diastolic dysfunction than in systolic dysfunction.

Topics: Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiac Output; Cardiomyopathies; Cardiovascular Agents; Coronary Disease; Diastole; Diuretics; Echocardiography; Electrocardiography; Heart Failure; Humans; Ventricular Dysfunction, Left

To review evaluation and treatment of patients with ventricular arrhythmias, based on recent studies, with an emphasis on randomized controlled trials.. MEDLINE search of English-language publications of ventricular arrhythmias and their references from 1966 through April 27, 1998. References to articles were also scanned to broaden the search.. Randomized controlled trials and all large nonrandomized trials of arrhythmias and arrhythmia therapy were reviewed. In addition, studies that led to changes in approach to patients with arrhythmias were reviewed.. We reviewed articles jointly for pertinent studies and information.. The goals of treatment of the patient with ventricular arrhythmias are to suppress symptoms and prevent a fatal event. The steps in providing such therapy include defining the cardiac anatomy, assessing arrhythmia risk through noninvasive or invasive testing, and prescribing treatment based on these results. Patients may be separated into high- and low-risk groups to help identify appropriate treatment. While low-risk groups may benefit from reassurance or medications such as beta-blockers or verapamil, high-risk groups have been more difficult to treat. Recent randomized trials of implantable cardioverter defibrillators for ventricular arrhythmias suggest that they may provide better protection for high-risk patients than do antiarrhythmic medications.. Treatment and understanding of risk from ventricular arrhythmias have advanced substantially in recent years. Classifying patients as being at high or low risk for fatal arrhythmias allows the physician to identify appropriate treatments for the high-risk patient without exposing the low-risk patient to unnecessary treatment-related risks.

Topics: Algorithms; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiac Surgical Procedures; Cardiovascular Agents; Catheter Ablation; Clinical Trials as Topic; Defibrillators, Implantable; Electrocardiography; Electrophysiology; Humans; Lidocaine; Risk Assessment; Survival Analysis; Tachycardia, Ventricular; Ventricular Dysfunction, Left; Ventricular Fibrillation

Topics: Aged; Cardiovascular Agents; Diastole; Drug Therapy, Combination; Heart Failure; Humans; Prognosis; Ventricular Dysfunction, Left

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Anticoagulants; Cardiovascular Agents; Female; Heart Failure; Humans; Male; Mineralocorticoid Receptor Antagonists; Platelet Aggregation Inhibitors; Systole; United States; Ventricular Dysfunction, Left

With the methods available today, most patients who arrive at the emergency department with acute cardiogenic pulmonary edema can be treated quickly and effectively. Modern pharmacologic therapy is based on directly counteracting the physiologic abnormalities that cause pulmonary edema. Agents that are useful in reducing LV preload and afterload and in managing hypotension are nitroglycerin, ACE inhibitors, vasodilators, vasopressors, and bipyrines. Noninvasive pressure support ventilation helps patients with pulmonary edema by decreasing the work of breathing, enhancing oxygen and carbon dioxide exchange, and increasing cardiac output. Use of BiPAP systems in emergency departments has averted endotracheal intubation in about 90% of patients with pulmonary edema who are experiencing acute respiratory failure.

Topics: Acute Disease; Cardiovascular Agents; Combined Modality Therapy; Emergency Treatment; Humans; Positive-Pressure Respiration; Pulmonary Edema; Ventricular Dysfunction, Left

Systolic heart failure leads to progressive left ventricular impairment, has a poor prognosis and negatively affects the patient's quality of life, especially when the disease advances to the point where it causes refractory symptoms. Ventricular remodeling, one of the consequences of advanced systolic heart failure, results from complex pathophysiologic mechanisms and leads to hemodynamic compromise, clinical deterioration and death. The nursing literature on heart failure has focused on neuroendocrine changes and the pharmacologic management in response to these changes. Little emphasis has been placed on other pathophysiologic mechanisms that lead to a worsening of ventricular function or on advances in clinical research that may influence current and future nursing management of the patient throughout the continuum of care. For therapy to be individualized, it is necessary for nurses to understand the pathophysiology of systolic heart failure and the importance that nursing actions have on augmenting medical management to alleviate symptoms and to deter the progression of the pathophysiologic state. Such an understanding should ultimately reduce morbidity and mortality and optimize quality of life.

Topics: Cardiovascular Agents; Heart Failure; Heart-Assist Devices; Humans; Patient Care Planning; Ventricular Dysfunction, Left; Ventricular Remodeling

Our understanding of cardiac failure has greatly changed over the last 15 years. Left ventricular diastolic dysfunction, which is now recognised as one of the primary causes of certain types of cardiac failure (1). Abnormal left ventricular diastolic function is the common determinant and indeed the earliest sign of all chronic left ventricular failures whether systolic left ventricular dysfunction is associated with it or not (2). In this paper, we review the basis of diastolic dysfunction and its impact on diagnosis and treatment of cardiac failure.

Topics: Aged; Aging; Cardiovascular Agents; Diastole; Drug Therapy, Combination; Electrocardiography; Humans; Prognosis; Ventricular Dysfunction, Left

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: Cardiovascular Agents; Diastole; Heart; Heart Failure; Heart Ventricles; Humans; Models, Biological; Systole; Ventricular Dysfunction, Left

Topics: Cardiovascular Agents; Diastole; Echocardiography; Heart Failure; Humans; Ventricular Dysfunction, Left

Heart failure is a major and increasing public health problem. Coronary artery disease has become the major etiology of heart failure. The differentiation of viable from nonviable myocardium in patients with coronary disease and impaired left ventricular systolic function is an issue of extreme importance to the clinician. Several diagnostic modalities including thallium imaging, dobutamine stress echocardiography, and positron emission tomography have gained considerable acceptance as useful tools in detecting myocardial viability. The management of heart failure with preserved left ventricular systolic function includes the use of beta blockers, calcium channel blockers, and nitrates. In patients with heart failure and impaired left ventricular systolic function, angiotensin converting enzyme inhibitors have become an integral part of the medical management. In patients whose angina is unresponsive to the addition of nitrates, a trial of bet blockers should be attempted and first generation calcium blockers should be avoided. Revascularization should always be sought, particularly when myocardial viability has been established.

Topics: Cardiovascular Agents; Coronary Disease; Heart Failure; Humans; Myocardial Revascularization; Ventricular Dysfunction, Left

More than 2 million Americans have heart failure, and about 400,000 new cases are diagnosed each year. Mortality is high, with 5-year mortality in the range of 50 percent. Many of the almost 1 million hospitalizations each year for heart failure might be prevented by improved evaluation and care. This Quick Reference Guide for Clinicians summarizes major recommendations in Heart Failure: Evaluation and Care of Patients with Left-Ventricular Systolic Dysfunction. Clinical Practice Guideline No. 11. The document was prepared by RAND, a nonprofit research and policy organization, and a private-sector panel of experts and consumers. Guideline recommendations are intended for use by a broad range of health care practitioners. The guideline recommendations are based on a combination of evidence obtained through extensive literature reviews and on expert judgment where evidence was lacking. Specific recommendations are made in the following areas: Prevention of heart failure with asymptomatic left-ventricular systolic dysfunction. Approaches to diagnosis and initial evaluation of suspected heart failure. Hospital admission and discharge criteria. Pharmacological management. Patient counseling and education. Exercise and rehabilitation. Evaluation for myocardial revascularization. Patient monitoring and followup evaluation.

Topics: Algorithms; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Coronary Artery Bypass; Counseling; Diuretics; Heart Failure; Heart Transplantation; Humans; Patient Education as Topic; Ventricular Dysfunction, Left

Exercise limitation is a cardinal manifestation of heart failure with reduced ejection fraction (HFrEF) but is not consistently improved by any of the current guideline-directed medical therapies.. To determine whether omecamtiv mecarbil, a novel direct myosin activator that improves cardiac performance and reduces the risk for cardiovascular death or first HF event in HFrEF, can improve peak exercise capacity in patients with chronic HFrEF.. Phase 3, double-blind, placebo-controlled randomized trial of patients with HFrEF (left ventricular ejection fraction ≤35%), New York Heart Association class II-III symptoms, N-terminal pro-B-type natriuretic peptide level of 200 pg/mL or greater, and baseline peak oxygen uptake (V̇o2) of 75% or less of predicted. Patients were randomized in a 2:1 ratio (omecamtiv mecarbil to placebo) between March 2019 and May 2021 at 63 sites in North America and Europe, with the last patient visit occurring on November 29, 2021.. Omecamtiv mecarbil (n = 185) or matching placebo (n = 91), given orally twice daily at a dose of 25 mg, 37.5 mg, or 50 mg based on target plasma levels, for 20 weeks.. The primary end point was a change in exercise capacity (peak V̇o2) from baseline to week 20. Secondary end points included total workload, ventilatory efficiency, and daily physical activity as determined by accelerometry.. Among 276 patients who were randomized (median age, 64 years; IQR, 55-70 years; 42 women [15%]), 249 (90%) completed the trial. The median left ventricular ejection fraction was 28% (IQR, 21-33) and the median baseline peak V̇o2 was 14.2 mL/kg/min (IQR, 11.6-17.4) in the omecamtiv mecarbil group and 15.0 mL/kg/min (IQR, 12.0-17.2) in the placebo group. Mean change in peak V̇o2 did not differ significantly between the omecamtiv mecarbil and placebo groups (mean, -0.24 mL/kg/min vs 0.21 mL/kg/min; least square mean difference, -0.45 mL/kg/min [95% CI, -1.02 to 0.13]; P = .13). Adverse events included dizziness (omecamtiv mecarbil: 4.9%, placebo: 5.5%), fatigue (omecamtiv mecarbil: 4.9%, placebo: 4.4%), heart failure events (omecamtiv mecarbil: 4.9%, placebo: 4.4%), death (omecamtiv mecarbil: 1.6%, placebo: 1.1%), stroke (omecamtiv mecarbil: 0.5%, placebo: 1.1%), and myocardial infarction (omecamtiv mecarbil: 0%, placebo: 1.1%).. In patients with chronic HFrEF, omecamtiv mecarbil did not significantly improve exercise capacity over 20 weeks compared with placebo. These findings do not support the use of omecamtiv mecarbil for treatment of HFrEF for improvement of exercise capacity.. ClinicalTrials.gov Identifier: NCT03759392.

Topics: Aged; Cardiovascular Agents; Chronic Disease; Double-Blind Method; Exercise Tolerance; Female; Heart Failure; Humans; Male; Middle Aged; Stroke Volume; Urea; Ventricular Dysfunction, Left; Ventricular Function, Left

Ivabradine has potent actions in reducing heart rate and improving clinical outcomes of chronic heart failure with reduced ejection fraction (HFrEF). At present, only the short-acting formulation of ivabradine is available that needs to be administered twice daily.. This study sought to evaluate the role of ivabradine hemisulfate sustained release (SR), a novel long-acting formulation of ivabradine dosed once daily, in stable patients with HFrEF.. Patients with stabilized HFrEF in New York Heart Association functional class II-IV were enrolled and randomized to receive placebo or ivabradine SR in addition to standard medications. The primary endpoint was the change of left ventricular (LV) end-systolic volume index from baseline to week 32.. We randomly assigned 181 patients to placebo and 179 patients to ivabradine SR. After 32 weeks, a significant improvement of LV end-systolic volume index from baseline was observed in both arms with a greater effect in the ivabradine SR arm. Ivabradine SR therapy also exhibited superiority in improving LV end-diastolic volume index, LV ejection fraction, resting heart rate, the Kansas City Cardiomyopathy Questionnaire score, and hospital admission for heart failure worsening and cardiovascular disease in comparison to placebo. Overall adverse events showed no difference between the treatment arms. There were fewer occurrences of worsening heart failure in the ivabradine SR arm.. The present study demonstrates that ivabradine SR once daily in addition to optimum standard therapy improved heart function in patients with HFrEF. (Clinical Trial of Systolic Heart Failure Treatment of IvabRadine Hemisulfate Sustained-release Tablets [FIRST]; NCT02188082).

Topics: Benzazepines; Cardiovascular Agents; Delayed-Action Preparations; Double-Blind Method; Heart Failure; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

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

There is no proven medical therapy that attenuates adverse left ventricular remodeling in patients with chronic primary mitral regurgitation (CPMR). Identification of molecular pathways important in the progression of left ventricular remodeling in patients with CPMR may lead to development of new therapeutic strategies.. We performed baseline echocardiographic, cardiac catheterization, and serum NT-pro-BNP analysis in patients with severe CPMR awaiting mitral valve surgery and stratified the study population into compensated or decompensated CPMR. We obtained left ventricular endomyocardial biopsies (n=12) for mRNA expression analysis, and compared baseline transcript levels of 109 genes important in volume-overload left ventricular remodeling with levels in normal hearts (n=5) and between patients with compensated (n=6) versus decompensated (n=6) CPMR. Patients were then randomized to treatment with and without carvedilol and followed until the time of surgery (mean follow-up 8.3 months) when repeat endomyocardial biopsies were obtained to correlate transcriptional dynamics with indices of adverse remodeling. CPMR was associated with increased. Transition to decompensated CPMR is associated with calcium dysregulation, increased expression of inflammatory, extracellular matrix and apoptotic genes, and downregulation of genes important in bioenergetics. These changes are not attenuated by carvedilol therapy and highlight the need for development of specific combinatorial therapies, targeting myocardial inflammation and apoptosis, together with urgent surgical or percutaneous valve interventions.

Topics: Adult; Cardiovascular Agents; Carvedilol; Chronic Disease; Gene Expression Profiling; Humans; Middle Aged; Mitral Valve Insufficiency; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling; Young Adult

In patients with type 2 diabetes, inhibitors of sodium-glucose cotransporter 2 (SGLT2) reduce the risk of a first hospitalization for heart failure, possibly through glucose-independent mechanisms. More data are needed regarding the effects of SGLT2 inhibitors in patients with established heart failure and a reduced ejection fraction, regardless of the presence or absence of type 2 diabetes.. In this phase 3, placebo-controlled trial, we randomly assigned 4744 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either dapagliflozin (at a dose of 10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of worsening heart failure (hospitalization or an urgent visit resulting in intravenous therapy for heart failure) or cardiovascular death.. Over a median of 18.2 months, the primary outcome occurred in 386 of 2373 patients (16.3%) in the dapagliflozin group and in 502 of 2371 patients (21.2%) in the placebo group (hazard ratio, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). A first worsening heart failure event occurred in 237 patients (10.0%) in the dapagliflozin group and in 326 patients (13.7%) in the placebo group (hazard ratio, 0.70; 95% CI, 0.59 to 0.83). Death from cardiovascular causes occurred in 227 patients (9.6%) in the dapagliflozin group and in 273 patients (11.5%) in the placebo group (hazard ratio, 0.82; 95% CI, 0.69 to 0.98); 276 patients (11.6%) and 329 patients (13.9%), respectively, died from any cause (hazard ratio, 0.83; 95% CI, 0.71 to 0.97). Findings in patients with diabetes were similar to those in patients without diabetes. The frequency of adverse events related to volume depletion, renal dysfunction, and hypoglycemia did not differ between treatment groups.. Among patients with heart failure and a reduced ejection fraction, the risk of worsening heart failure or death from cardiovascular causes was lower among those who received dapagliflozin than among those who received placebo, regardless of the presence or absence of diabetes. (Funded by AstraZeneca; DAPA-HF ClinicalTrials.gov number, NCT03036124.).

Topics: Aged; Benzhydryl Compounds; Cardiovascular Agents; Cardiovascular Diseases; Combined Modality Therapy; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glucosides; Glycated Hemoglobin; Heart Failure; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume; Ventricular Dysfunction, Left

This study was designed to investigate the agreement of 2D transthoracic echocardiography (2D TTE) with cardiovascular magnetic resonance imaging (CMR) in a contemporary population of ST-elevation myocardial infarction (STEMI) patients.. In this subanalysis of the GIPS-III trial, a randomized controlled trial investigating the administration of metformin in STEMI patients to prevent reperfusion injury, we studied 259 patients who underwent same-day CMR and 2D TTE assessments four months after hospitalization for a first STEMI. Bland-Altman analyses were performed to assess agreement between LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV ejection fraction (LVEF), and LV mass measurements. Sensitivity and specificity of 2D TTE to detect categories of LVEF (≤35%, 35-50%, ≥50%) was determined. Linear regression of absolute differences in measurements between imaging modalities was used to investigate whether patient characteristics impact measurement bias.. Pairwise difference (bias) and 95% limits of agreement between CMR and 2D TTE measurements were +84 (37, 147) ml for LVEDV, +39 (6, 85) ml for LVESV, -1.1 ± 13.5% for LVEF, and -75 (-154, -14) g for LV mass. Sensitivity and specificity of 2D TTE to detect subjects with moderately depressed LVEF (35-50%) as measured by CMR were 52% and 88% respectively. We observed a significant effect of enzymatic infarct size on bias between 2D TTE and CMR in measuring LVESV and LVEF (P = 0.029, P = 0.001 respectively), of age and sex on bias between 2D TTE and CMR in measuring LV mass (P = 0.027, P < 0.001) and LVEDV (P = 0.001, P = 0.039), and of heart rate on bias between 2D TTE and CMR in LV volume measurements (P = 0.004, P = 0.016).. Wide limits of agreement, underestimation of LV volumes and overestimation of LV mass was observed when comparing 2D TTE to CMR. Enzymatic infarct size, age, sex, and heart rate are potential sources of bias between imaging modalities.

Topics: Cardiovascular Agents; Drug Administration Schedule; Echocardiography; Female; Heart Ventricles; Humans; Magnetic Resonance Angiography; Male; Metformin; Middle Aged; Multimodal Imaging; Myocardial Reperfusion Injury; Reproducibility of Results; Sensitivity and Specificity; ST Elevation Myocardial Infarction; Ventricular Dysfunction, 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: Aged; Benzazepines; Cardiovascular Agents; Chronic Disease; Cyclic Nucleotide-Gated Cation Channels; Echocardiography, Doppler, Pulsed; Female; Heart Failure; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Pulse Wave Analysis; Severity of Illness Index; Sinoatrial Node; Treatment Outcome; Ventricular Dysfunction, Left

Low cardiac output syndrome is associated with increased mortality and occurs in 3% to 14% of patients undergoing cardiac surgery on cardiopulmonary bypass (CPB). Levosimendan, a novel calcium sensitizer and K. LEVO-CTS, a large randomized multicenter clinical trial, will evaluate the efficacy, safety, and cost-effectiveness of levosimendan in reducing adverse outcomes in high-risk patients undergoing cardiac surgery on CPB.. ClinicalTrials.gov (NCT02025621).

Topics: Administration, Intravenous; Adult; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Cardiovascular Agents; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Hydrazones; Male; Middle Aged; Postoperative Complications; Pyridazines; Simendan; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left

To study the hemodynamic effect of levosimendan administration in acute heart failure patients with severe aortic stenosis (AS) and reduced left ventricular ejection fraction (LVEF).. Hemodynamic response to 24 h intravenous levosimendan infusion (0.1 μg/kg/min without a loading dose) in patients with severe AS (aortic valve area ≤1 cm(2) , time-velocity integral between left ventricular out-flow tract and aortic valve <0.25), reduced LVEF (≤40%), and a depressed cardiac index (CI) <2.2 L/min/m(2) was determined in a sequential group of nine patients aged 76 ± 10 years (5 men).. Baseline mean ejection fraction was 33 ± 0.7%; mean aortic valve area was 0.37 ±0.11 cm(2) /m(2) ; peak and mean gradients of 63.6 ± 20.53 and 36.7 ± 12.62 mmHg, respectively; and mean CI was 1.65 ± 0.20 L/min/m(2) . At 6 and 12 h of levosimendan therapy, mean CI had increased to 2.00 ± 0.41 L/min/m(2) (P = 0.02) and 2.17 ± 0.40 L/min/m(2) (P = 0.01), respectively. At 24 h, mean CI had increased further to 2.37 ± 0.49 L/min/m(2) (P = 0.01). A significant beneficial effect was also observed in pulmonary capillary wedge pressure, pulmonary artery mean pressure, central venous pressure, systemic vascular resistances, pulmonary vascular resistances, stroke volume index, left ventricular stroke work index. NTproBNP levels decreased at 24 h of levosimendan treatment. Levosimendan infusion was also well tolerated. Five patients subsequently underwent aortic valve surgery replacement. One died (of postoperative multiorgan failure). At 30 days, overall survival was 75%.. Levosimendan administration improves hemodynamic parameters in critically ill patients with severe AS and reduced LVEF. In our study, it provides a safe and effective bridge to aortic-valve replacement or oral vasodilator therapy in surgical contraindicated patients. A controlled study is needed to confirm these preliminary findings.

Topics: Aged; Aged, 80 and over; Aortic Valve Stenosis; Cardiovascular Agents; Critical Illness; Female; Heart Failure; Hemodynamics; Humans; Hydrazones; Infusions, Intravenous; Male; Middle Aged; Pyridazines; Recovery of Function; Severity of Illness Index; Simendan; Spain; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

To: (i) describe the baseline characteristics of patients in ATMOSPHERE and the changes in the planned analysis of ATMOSPHERE resulting from the mandated discontinuation of study treatment in patients with diabetes; (ii) compare the baseline characteristics of patients in ATMOSPHERE with those in the Prospective comparison of Angiotensin Receptor neprilysin inhibitors with Angiotensin converting enzyme inhibitors to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF); and (iii) compare the characteristics of patients with and without diabetes at baseline in ATMOSPHERE.. A total of 7063 patients were randomized into ATMOSPHERE April 2009-April 2014 at 755 sites in 43 countries. Their average age was 63 years and 78% were men. ATMOSPHERE patients were generally similar to those in PARADIGM-HF although fewer had diabetes, renal dysfunction, and were treated with a mineralocorticoid receptor antagonist. In ATMOSPHERE, patients with diabetes differed in numerous ways from those without. Patients with diabetes were older and had worse heart failure status but a similar left ventricular ejection fraction (mean 28%); they had a higher body mass index and more co-morbidity, especially hypertension and coronary heart disease. Mean estimated glomerular filtration rate was slightly lower in those with diabetes compared with those without.. ATMOSPHERE will determine whether patients with HF and reduced ejection fraction (particularly those without diabetes) benefit from the addition of a direct renin inhibitor to standard background therapy, including an angiotensin-converting enzyme inhibitor, beta-blocker, and a mineralocorticoid receptor antagonist. ATMOSPHERE will also determine whether aliskiren alone is superior to, or at least non-inferior to, enalapril.

Topics: Amides; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Diabetes Mellitus; Drug Therapy, Combination; Enalapril; Female; Fumarates; Heart Failure; Humans; Male; Middle Aged; Renin; Stroke Volume; Ventricular Dysfunction, Left

The study objective was to identify the predictors of outcomes in a contemporary cohort of patients from the Reduction in cardiovascular Events by acaDesine in patients undergoing CABG (RED-CABG) trial. Despite the increasing risk profile of patients who undergo coronary artery bypass grafting, morbidity and mortality have remained low, and identification of the current predictors of adverse outcomes may permit new treatments to further improve outcomes.. The RED-CABG trial was a multicenter, randomized, double-blind, placebo-controlled study that determined that acadesine did not reduce adverse events in moderately high-risk patients undergoing nonemergency coronary artery bypass grafting. The primary efficacy end point was a composite of all-cause death, nonfatal stroke, or the need for mechanical support for severe left ventricular dysfunction through postoperative day 28. Logistic regression modeling with stepwise variable selection identified which prespecified baseline characteristics were associated with the primary outcome. A second logistic model included intraoperative variables as potential covariates.. The 4 independent preoperative risk factors predictive of the composite end point were (1) a history of heart failure (odds ratio, 2.9); (2) increasing age (odds ratio, 1.033 per decade); (3) a history of peripheral vascular disease (odds ratio, 1.6); and (4) receiving aspirin before coronary artery bypass grafting (odds ratio, 0.5), which was protective. The duration of the cardiopulmonary bypass (odds ratio, 1.8) was the only intraoperative variable that contributed to adverse outcomes.. Patients who had heart failure and preserved systolic function had a similar high risk of adverse outcomes as those with low ejection fractions, and new approaches may mitigate this risk. Recognition of patients with excessive atherosclerotic burden may permit perioperative interventions to improve their outcomes. The contemporary risks of coronary artery bypass grafting have changed, and their identification may permit new methods to improve outcomes.

Topics: Age Factors; Aminoimidazole Carboxamide; Aspirin; Cardiopulmonary Bypass; Cardiovascular Agents; Chi-Square Distribution; Coronary Artery Bypass; Double-Blind Method; Heart Failure; Humans; Logistic Models; Multivariate Analysis; Odds Ratio; Patient Selection; Peripheral Arterial Disease; Protective Factors; Ribonucleosides; Risk Assessment; Risk Factors; Stroke; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Assuming that coronary interventions, both coronary bypass surgery (CABG) and percutaneous coronary intervention (PCI), are directed to preserve left ventricular function, it is not known whether medical therapy alone (MT) can achieve this protection. Thus, we evaluated the evolution of LV ejection fraction (LVEF) in patients with stable coronary artery disease (CAD) treated by CABG, PCI, or MT as a post hoc analysis of a randomized controlled trial with a follow-up of 10 years.. Left ventricle ejection fraction was assessed with transthoracic echocardiography in patients with multivessel CAD, participants of the MASS II trial before randomization to CABG, PCI, or MT, and re-evaluated after 10 years of follow-up.. Of the 611 patients, 422 were alive after 10.32 ± 1.43 years. Three hundred and fifty had LVEF reassessed: 108 patients from MT, 111 from CABG, and 131 from PCI. There was no difference in LVEF at the beginning (0.61 ± 0.07, 0.61 ± 0.08, 0.61 ± 0.09, respectively, for PCI, CABG, and MT, P = 0.675) or at the end of follow-up (0.56 ± 0.11, 0.55 ± 0.11, 0.55 ± 0.12, P = 0.675), or in the decline of LVEF (reduction delta of -7.2 ± 17.13, -9.08 ± 18.77, and -7.54 ± 22.74). Acute myocardial infarction (AMI) during the follow-up was associated with greater reduction in LVEF. The presence of previous AMI (OR: 2.50, 95% CI: 1.40-4.45; P = 0.0007) and during the follow-up (OR: 2.73, 95% CI: 1.25-5.92; P = 0.005) was associated with development of LVEF <45%.. Regardless of the therapeutic option applied, LVEF remains preserved in the absence of a major adverse cardiac event after 10 years of follow-up.. http://www.controlled-trials.com. Registration number ISRCTN66068876.

Topics: Aged; Analysis of Variance; Cardiovascular Agents; Coronary Artery Bypass; Coronary Stenosis; Echocardiography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Percutaneous Coronary Intervention; Stroke; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left

The Biventricular Pacing After Cardiac Surgery trial investigates hemodynamics of temporary pacing in selected patients at risk of left ventricular dysfunction. This trial demonstrates improved hemodynamics during optimized biventricular pacing compared with atrial pacing at the same heart rate 1 and 2 hours after bypass and reduced vasoactive-inotropic score over the first 4 hours after bypass. However, this advantage of biventricular versus atrial pacing disappears 12 to 24 hours later. We hypothesized that changes in intrinsic heart rate can explain variable effects of atrial pacing in this setting.. Heart rate, mean arterial pressure, cardiac output, and medications depressing heart rate were analyzed in patients randomized to continuous biventricular pacing (n = 16) or standard of care (n = 18).. During 30-second testing periods without pacing, intrinsic heart rate was lower in the paced group 12 to 24 hours after bypass (76.5 ± 17.5 vs 91.7 ± 13.0 beats per minute; P = .040) but not 1 or 2 hours after bypass. Cardiac output (4.4 ± 1.2 vs 3.6 ± 1.9 L/min; P = .054) and stroke volume (53 ± 2 vs 42 ± 2 mL; P = .051) increased overnight in the paced group. Vasoactive medication doses were not different between groups, whereas dexmedetomidine administration was prolonged over postoperative hours 12 to 24 in the paced group (793 ± 528 vs 478 ± 295 minutes; P = .013).. These observations suggest that hemodynamic benefits of biventricular pacing 12 to 24 hours after cardiopulmonary bypass lead to withdrawal of sympathetic drive and decreased intrinsic heart rate. Depression of intrinsic rate increases the apparent benefit of atrial pacing in the chronically paced group but not in the control group. Additional study is needed to define clinical benefits of these effects.

Topics: Aged; Arterial Pressure; Cardiac Output; Cardiac Resynchronization Therapy; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Cardiovascular Agents; Critical Care; Female; Heart Atria; Heart Rate; Humans; Male; Middle Aged; New York City; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

We assessed the relationship between diabetes and cardiac structure and function following myocardial infarction (MI) and whether diabetes influences the effect of direct renin inhibition on change in left ventricular (LV) size.. The ASPIRE trial enrolled 820 patients 2-8 weeks after MI with ejection fraction ≤ 45% and randomized them to the direct renin inhibitor aliskiren (n= 423) or placebo (n = 397) added to standard medical therapy. Echocardiography was performed at baseline and after 36 weeks in 672 patients with evaluable paired studies. Compared with non-diabetic patients, diabetic patients (n = 214) were at higher risk for a composite of cardiovascular (CV) death, heart failure hospitalization, recurrent MI, stroke, or aborted sudden death (14 vs. 7%; adjusted hazard ratio 1.63, 95% confidence interval 1.01-2.64, P= 0.045), despite similar left ventricular ejection fraction (37.9 ± 5.3 vs. 37.6 ± 5.2%, P= 0.48) and end-systolic volume (ESV) (84 ± 25 vs. 82 ± 28 mL, P= 0.46). Diabetic patients demonstrated greater concentric remodelling (relative wall thickness 0.38 ± 0.07 vs. 0.36 ± 0.07, P= 0.0002) and evidence of higher LV filling pressure (E/E' 11.1 ± 5.3 vs. 9.1 ± 4.3, P= 0.0011). At 36 weeks, diabetic patients experienced similar per cent reduction in ESV overall (-4.9 ± 17.9 vs. -5.5 ± 16.9, P= 0.67) but tended to experience greater reduction in ESV than non-diabetic patients when treated with aliskiren (interaction P = 0.08).. Compared with non-diabetic patients, diabetic patients are at increased risk of CV events post-MI despite no greater LV enlargement or reduction in systolic function. Diabetic patients demonstrate greater concentric remodelling and evidence of higher LV filling pressure, suggesting diastolic dysfunction as a potential mechanism for the higher risk observed among these patients.

Topics: Aged; Amides; Cardiovascular Agents; Diabetic Cardiomyopathies; Diastole; Double-Blind Method; Female; Fumarates; Humans; Male; Middle Aged; Myocardial Infarction; Renin; Systole; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

The long-term benefits of the maze procedure in patients with chronic atrial fibrillation undergoing mechanical valve replacement who already require lifelong anticoagulation remain unclear.. We evaluated adverse outcomes (death; thromboembolic events; composite of death, heart failure, or valve-related complications) in 569 patients with atrial fibrillation-associated valvular heart disease who underwent mechanical valve replacement with (n=317) or without (n=252) a concomitant maze procedure between 1999 and 2010. After adjustment for differences in baseline risk profiles, patients who had undergone the maze procedure were at similar risks of death (hazard ratio, 1.15; 95% confidence interval, 0.65-2.03; P=0.63) and the composite outcomes (hazard ratio, 0.82; 95% confidence interval, 0.50-1.34; P=0.42) but a significantly lower risk of thromboembolic events (hazard ratio, 0.29; 95% confidence interval, 0.12-0.73; P=0.008) compared with those who underwent valve replacement alone at a median follow-up of 63.6 months (range, 0.2-149.9 months). The effect of superior event-free survival by the concomitant maze procedure was notable in a low-risk EuroSCORE (0-3) subgroup (P=0.049), but it was insignificant in a high-risk EuroSCORE (≥4) subgroup (P=0.65). Furthermore, the combination of the maze procedure resulted in superior left ventricular (P<0.001) and tricuspid valvular functions (P<0.001) compared with valve replacement alone on echocardiographic assessments performed at a median of 52.7 months (range, 6.0-146.8 months) after surgery.. Compared with valve replacement alone, the addition of the maze procedure was associated with a reduction in thromboembolic complications and improvements in hemodynamic performance in patients undergoing mechanical valve replacement, particularly in those with low risk of surgery.

Topics: Adult; Aged; Anticoagulants; Atrial Appendage; Atrial Fibrillation; Cardiovascular Agents; Catheter Ablation; Combined Modality Therapy; Cryosurgery; Endocarditis; Female; Heart Valve Prosthesis Implantation; Hemodynamics; Humans; Kaplan-Meier Estimate; Male; Microwaves; Middle Aged; Mitral Valve Insufficiency; Postoperative Complications; Postoperative Hemorrhage; Prospective Studies; Thromboembolism; Treatment Outcome; Tricuspid Valve Insufficiency; Ultrasonography; Ventricular Dysfunction, Left

The goal of this study was to make a head-to-head comparison of 2 common forms of multidisciplinary chronic heart failure (CHF) management.. Although direct patient contact appears to be best in delivering CHF management overall, the precise form to optimize health outcomes is less clear.. This prospective, multicenter randomized controlled trial with blinded endpoint adjudication comprised 280 hospitalized CHF patients (73% male, age 71 ± 14 years, and 73% with left ventricular ejection fraction ≤45%) randomized to home-based intervention (HBI) or specialized CHF clinic-based intervention (CBI). The primary endpoint was all-cause, unplanned hospitalization or death during 12- to 18-month follow-up. Secondary endpoints included type/duration of hospitalization and healthcare costs.. The primary endpoint occurred in 102 of 143 (71%) HBI versus 104 of 137 (76%) CBI patients (adjusted hazard ratio [HR]: 0.97 [95% confidence interval (CI): 0.73 to 1.30], p = 0.861): 96 (67.1%) HBI versus 95 (69.3%) CBI patients had an unplanned hospitalization (p = 0.887), and 31 (21.7%) versus 38 (27.7%) died (p = 0.252). The median duration of each unplanned hospitalization was significantly less in the HBI group (4.0 [interquartile range (IQR): 2.0 to 7.0] days vs. 6.0 [IQR: 3.5 to 13] days; p = 0.004). Overall, 75% of all hospitalization was attributable to 64 (22.9%) patients, of whom 43 (67%) were CBI patients (adjusted odds ratio: 2.55 [95% CI: 1.37 to 4.73], p = 0.003). HBI was associated with significantly fewer days of all-cause hospitalization (-35%; p = 0.003) and from cardiovascular causes (-37%; p = 0.025) but not for CHF (-24%; p = 0.218). Consequently, healthcare costs ($AU3.93 vs. $AU5.53 million) were significantly less for the HBI group (median: $AU34 [IQR: 13 to 81] per day vs. $AU52 [17 to 140] per day; p = 0.030).. HBI was not superior to CBI in reducing all-cause death or hospitalization. However, HBI was associated with significantly lower healthcare costs, attributable to fewer days of hospitalization. (Which Heart failure Intervention is most Cost-effective & consumer friendly in reducing Hospital care [WHICH?]; ACTRN12607000069459).

Topics: Aged; Aged, 80 and over; Ambulatory Care; Australia; Cardiovascular Agents; Chronic Disease; Cohort Studies; Cost-Benefit Analysis; Female; Follow-Up Studies; Heart Failure; Home Care Services; Humans; Length of Stay; Male; Middle Aged; Patient Readmission; Prospective Studies; Quality of Life; Stroke Volume; Surveys and Questionnaires; Ventricular Dysfunction, Left

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

To assess the effect of Shenmai Injection (SMI) on left ventricular diastolic function (LVDF) in patients with chronic heart failure (CHF) by tissue Doppler imaging (TDI).. Sixty-four CHF patients were randomly assigned to two groups, the observation group and the control group. Basic treatment including polarized liquid therapy was given to all the patients. In addition, SMI was given to patients of the observation group. The treatment duration was 14 days. TDI was performed in all the patients 3 days prior to the initiation of the treatment and one week after the medication to measure the average movement velocity of the mitral ring of the left ventricle at the early systolic stage and late diastolic stage (Ea and Aa); the outcomes were compared with the corresponding parameters obtained from blood flow Doppler echocardiography, namely, the velocity of the E-wave (E) and A-wave (A).. After treatment, Ea and Ea/Aa increased and Aa decreased significantly in the observation group (P<0.05). In the control group, although some improvement was seen, there was no statistically significant change (P>0.05). No statistical significance was shown between groups in these parameters after treatment.. TDI assessment shows that SMI could effectively improve the LVDF in CHF patients.

Topics: Adult; Aged; Cardiovascular Agents; Chronic Disease; Diastole; Drug Combinations; Drugs, Chinese Herbal; Echocardiography, Doppler; Female; Heart Failure, Diastolic; Humans; Injections; Male; Middle Aged; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function

The purpose of this study was to determine whether atrial pacing is a safe alternative to minimal (backup-only) ventricular pacing in defibrillator recipients with impaired ventricular function.. The DAVID (Dual Chamber and VVI Implantable Defibrillator) trial demonstrated that dual chamber rate responsive pacing as compared with ventricular backup-only pacing worsens the combined end point of mortality and heart failure hospitalization. Although altered ventricular activation from right ventricular pacing was presumed to be the likely cause for these maladaptive effects, this supposition is unproven.. In all, 600 patients with impaired ventricular function from 29 North American sites, who required an implanted defibrillator for primary or secondary prevention, with no clinical indication for pacing, were randomly assigned to atrial pacing (at 70 beats/min) versus minimal ventricular pacing (at 40 beats/min) and followed up for a mean of 2.7 years.. There were no significant differences between pacing arms in patients' baseline characteristics, use of heart failure medications, and combined primary end point of time to death or heart failure hospitalization during follow-up, with an overall incidence of 11.1%, 16.9%, and 24.6% at 1, 2, and 3 years, respectively. Similarly, the incidence of atrial fibrillation, syncope, appropriate or inappropriate shocks, and quality of life measures did not significantly differ between treatment groups.. The effect of atrial pacing on event-free survival and quality of life was not substantially worse than, and was likely equivalent to, backup-only ventricular pacing. Atrial pacing may be considered a "safe alternative" when pacing is desired in defibrillator recipients, but affords no clear advantage or disadvantage over a ventricular pacing mode that minimizes pacing altogether. (Dual Chamber and VVI Implantable Defibrillator [DAVID] Trial II; NCT00187187).

Topics: Aged; Atrial Fibrillation; Bradycardia; Cardiac Pacing, Artificial; Cardiovascular Agents; Combined Modality Therapy; Defibrillators, Implantable; Electric Countershock; Female; Heart Failure; Hospitalization; Humans; Incidence; Male; Middle Aged; Prosthesis Design; Quality of Life; Ventricular Dysfunction, Left

Ivabradine is a selective heart rate-lowering agent that acts by inhibiting the pacemaker current If in sinoatrial node cells. Patients with coronary artery disease and left ventricular dysfunction are at high risk of death and cardiac events, and the BEAUTIFUL study was designed to evaluate the effects of ivabradine on outcome in such patients receiving optimal medical therapy. This report describes the study population at baseline.. BEAUTIFUL is an international, multicentre, randomized, double-blind trial to compare ivabradine with placebo in reducing mortality and cardiovascular events in patients with stable coronary artery disease and left ventricular systolic dysfunction (ejection fraction <40%).. A total of 10,917 patients were randomized. At baseline, their mean age was 65 years, 83% were male, 98% Caucasian, 88% had previous myocardial infarction, 37% had diabetes, and 40% had metabolic syndrome. Mean ejection fraction was 32% and resting heart rate was 71.6 bpm. Concomitant medications included beta-blockers (87%), renin-angiotensin system agents (89%), antithrombotic agents (94%), and lipid-lowering agents (76%).. Main results from BEAUTIFUL are expected in 2008, and should show whether ivabradine, on top of optimal medical treatment, reduces mortality and cardiovascular events in this population of high-risk patients.

Topics: Aged; Benzazepines; Cardiovascular Agents; Coronary Artery Disease; Diabetes Complications; Double-Blind Method; Drug Therapy, Combination; Female; Heart Failure; Humans; Ivabradine; Male; Metabolic Syndrome; Middle Aged; Myocardial Infarction; Ventricular Dysfunction, Left

To study efficacy of the myocardial cytoprotector trimethasidine MB and metabolic drug 3-(2,2,2-trimethylhydrasine) propionate dihydrate (3-TMHP) in the treatment of chronic cardiac failure (CCF).. Sixty-five patients with CCF after myocardial infarction (> 6 months) with left ventricular ejection fraction (LV EF) <40% were randomized into 3 groups: group 1 (n=28) received basic therapy plus trimethasidine in a daily dose 70 mg; group 2 (n=25)--basic therapy plus 3-TMHP in a daily dose 1000 mg; control group (n=12) received basic therapy with ACE inhibitors, beta-blockers and diuretics. Before and after 6-month treatment all the patients have undergone stress echocardiography with dobutamine. Perfusion and myocardial metabolism were determined in 34 patients with single photon emission computed tomography of the myocardium (SPECT) with 99m-Tc-technetril and positron-emission tomography of the myocardium (PET) with F-18-fluorodesoxyglucose.. Groups 1 and 2 significantly reduced functional class of CCF and prolonged the distance of a 6-min walk. Significant improvement of life quality was observed only in the treatment with trimethasidine. According to PET, treatment with trimethasidine MB and 3-TMHP has an anti-ischemic action manifesting with a significant attenuation of glucose hypermetabolism in the ischemic segment to normal values. However, significant improvement of systolic thickening in hybernated segments by SPECT as well as a significant rise of LV EF were recorded only in the treatment with trimethasidine MB. Stress echocardiography with dobutamine had high specificity (85.7%) but low sensitivity (50.4%) in detection of hybernated myocardium.. Trimethasidine MB (preductal MB) has advantages over 3-TMHP, so it is preferable in ischemic CHF.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Chronic Disease; Combined Modality Therapy; Diuretics; Drug Administration Schedule; Female; Heart Failure; Humans; Male; Methylhydrazines; Middle Aged; Positron-Emission Tomography; Trimetazidine; Vasodilator Agents; Ventricular Dysfunction, Left

There are no randomized, controlled trial data to support the benefit of beta-blockers in patients with asymptomatic left ventricular systolic dysfunction. We investigated whether beta-blocker therapy ameliorates left ventricular remodeling in asymptomatic patients with left ventricular systolic dysfunction.. Patients with left ventricular ejection fraction <40%, mild left ventricular dilation, and no symptoms of heart failure (New York Heart Association class I) were randomly assigned to receive extended-release metoprolol succinate (Toprol-XL, AstraZeneca) 200 mg or 50 mg or placebo for 12 months. Echocardiographic assessments of left ventricular end-systolic volume, end-diastolic volume, mass, and ejection fraction were performed at baseline and at 6 and 12 months. The 149 patients randomized to the 3 treatment groups (200 mg, n=48; 50 mg, n=48; and placebo, n=53) were similar with regard to all baseline characteristics including age (mean, 66 years), gender (74% male), plasma brain natriuretic peptide (79 pg/mL), left ventricular end-diastolic volume index (110 mL/m2), and left ventricular ejection fraction (27%). At 12 months in the 200-mg group, there was a 14+/-3 mL/m2 decrease (least square mean+/-SE) in end-systolic volume index and a 6+/-1% increase in left ventricular ejection fraction (P<0.05 versus baseline and placebo for both). The decrease in end-diastolic volume index (14+/-3) was different from that seen at baseline (P<0.05) but not with placebo. In the 50-mg group, end-systolic and end-diastolic volume indexes decreased relative to baseline but were not different from what was seen with placebo, whereas ejection fraction increased by 4+/-1% (P<0.05 versus baseline and placebo).. Beta-blocker therapy can ameliorate left ventricular remodeling in asymptomatic patients with left ventricular systolic dysfunction.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiovascular Agents; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Heart Rate; Humans; Male; Metoprolol; Middle Aged; Natriuretic Peptide, Brain; Stroke Volume; Treatment Outcome; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Remodeling

Little is known about the management of elderly patients with congestive heart failure (CHF) although they represent the majority of the CHF population. Therefore, the TIME-CHF study was set up (1) to evaluate the medical management of very old patients (> or = 75 years) with CHF compared with younger patients (60-74 years), (2) to compare an intensified with a standard treatment approach, and (3) to differentiate between systolic and diastolic dysfunction (ejection fraction < or = 45% vs > 45%).. In a prospective single-blinded multicenter trial, 824 symptomatic patients, CHF hospitalization within the last year and elevated NT-BNP, are randomized to an intensified versus a standard medical therapy. Treatment strategies follow the published guidelines with the aim to reduce symptoms to NYHA class < or = II (standard) or, additionally, NT-BNP levels below twice the upper limit of normal (intensified). The primary end points are 18-month hospitalization-free survival and quality of life.. By the end of 2004, 297 patients have been included, 147 randomized to intensified and 150 to standard therapy. Mean age in the older age group was 82 +/- 4 years (n = 174) and 69 +/- 4 years in the younger group (n = 123), respectively. Ejection fraction was > 45% in 26% and 10%, respectively. Significant comorbidities were present in 93% of patients.. TIME-CHF will be the first prospective randomized trial to comprehensively study the management of elderly patients with CHF. It will provide unique information comparing two treatment strategies in two age groups irrespective of ejection fraction regarding prognosis, quality of life, as well as resource utilization and costs.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Diastole; Dose-Response Relationship, Drug; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Quality of Life; Research Design; Single-Blind Method; Stroke Volume; Survival Analysis; Systole; Ventricular Dysfunction, Left

The Homburg Biventricular Pacing Evaluation (HOBIPACE) is the first randomized controlled study that compares the biventricular (BV) pacing approach with conventional right ventricular (RV) pacing in patients with left ventricular (LV) dysfunction and a standard indication for antibradycardia pacing in the ventricle.. In patients with LV dysfunction and atrioventricular block, conventional RV pacing may yield a detrimental effect on LV function.. Thirty patients with standard indication for permanent ventricular pacing and LV dysfunction defined by an LV end-diastolic diameter > or =60 mm and an ejection fraction < or =40% were included. Using a prospective, randomized crossover design, three months of RV pacing were compared with three months of BV pacing with regard to LV function, N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum concentration, exercise capacity, and quality of life.. When compared with RV pacing, BV stimulation reduced LV end-diastolic (-9.0%, p = 0.022) and end-systolic volumes (-16.9%, p < 0.001), NT-proBNP level (-31.0%, p < 0.002), and the Minnesota Living with Heart Failure score (-18.9%, p = 0.01). Left ventricular ejection fraction (+22.1%), peak oxygen consumption (+12.0%), oxygen uptake at the ventilatory threshold (+12.5%), and peak circulatory power (+21.0%) were higher (p < 0.0002) with BV pacing. The benefit of BV over RV pacing was similar for patients with (n = 9) and without (n = 21) atrial fibrillation. Right ventricular function was not affected by BV pacing.. In patients with LV dysfunction who need permanent ventricular pacing support, BV stimulation is superior to conventional RV pacing with regard to LV function, quality of life, and maximal as well as submaximal exercise capacity.

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Bradycardia; Cardiac Pacing, Artificial; Cardiovascular Agents; Combined Modality Therapy; Cross-Over Studies; Exercise Tolerance; Female; Heart Block; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Quality of Life; Single-Blind Method; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

Patients with left ventricular dysfunction who are undergoing major noncardiac vascular surgery are at increased risk of adverse postoperative events. We sought to evaluate whether perioperative medication use, including angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, statins, and aspirin, was associated with a reduced incidence of postoperative in-hospital mortality in these high-risk patients. The study enrolled 511 patients with left ventricular dysfunction (left ventricular ejection fraction <30%) who were undergoing major noncardiac vascular surgery. Cardiac risk factors and medication use were noted before surgery. Preoperative dobutamine stress echocardiography (DSE) was performed to identify patients with stress-induced myocardial ischemia. The end point was postoperative in-hospital mortality. Univariate and multivariate logistic regression analyses were performed to evaluate the relation between perioperative medication use and mortality. The mean age of the study population was 64 +/- 11 years, and 75% were men. Perioperative use of ACE inhibitors, beta-blockers, statins, and aspirin was recorded in 215 (48%), 139 (27%), 107 (21%), and 125 patients (24%), respectively. Stress-induced myocardial ischemia occurred in 82 patients (16%). Sixty-four patients (13%) died. Perioperative use of ACE inhibitors (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.12-0.91), beta-blockers (OR, 0.03; 95% CI, 0.01-0.26), statins (OR, 0.06; 95% CI, 0.01-0.53), and aspirin (OR, 0.13; 95% CI, 0.03-0.55), was significantly associated with a reduced incidence of mortality, after adjusting for cardiac risk factors and DSE results. In conclusion, the present study showed that the perioperative use of ACE inhibitors, beta-blockers, statins, and aspirin is independently associated with a reduced incidence of in-hospital mortality in patients with left ventricular dysfunction who are undergoing major noncardiac vascular surgery.

Topics: Adrenergic beta-Agonists; Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Cardiovascular Agents; Dobutamine; Echocardiography; Endpoint Determination; Female; Heart Diseases; Hospital Mortality; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intraoperative Complications; Male; Middle Aged; Vascular Surgical Procedures; Ventricular Dysfunction, Left

Nearly 1 million hospitalizations for chronic heart failure occur yearly in the United States, with most related to worsening systemic congestion. Diuretic use, the mainstay therapy for congestion, is associated with electrolyte abnormalities and worsening renal function. In contrast to diuretics, the vasopressin antagonist tolvaptan may increase net volume loss in heart failure without adversely affecting electrolytes and renal function.. To evaluate the short- and intermediate-term effects of tolvaptan in patients hospitalized with heart failure.. Randomized, double-blind, placebo-controlled, parallel-group, dose-ranging, phase 2 trial conducted at 45 centers in the United States and Argentina and enrolling 319 patients with left ventricular ejection fraction of less than 40% and hospitalized for heart failure with persistent signs and symptoms of systemic congestion despite standard therapy.. After admission, patients were randomized to receive 30, 60, or 90 mg/d of oral tolvaptan or placebo in addition to standard therapy, including diuretics. The study drug was continued for up to 60 days.. In-hospital outcome was change in body weight at 24 hours after randomization; outpatient outcome was worsening heart failure (defined as death, hospitalization, or unscheduled visits for heart failure) at 60 days after randomization.. Median (interquartile range) body weight at 24 hours after randomization decreased by -1.80 (-3.85 to -0.50), -2.10 (-3.10 to -0.85), -2.05 (-2.80 to -0.60), and -0.60 (-1.60 to 0.00) kg in the groups receiving tolvaptan 30, 60, and 90 mg/d, and placebo, respectively (P< or =.008 for all tolvaptan groups vs placebo). The decrease in body weight with tolvaptan was not associated with changes in heart rate or blood pressure, nor did it result in hypokalemia or worsening renal function. There were no differences in worsening heart failure at 60 days between the tolvaptan and placebo groups (P =.88 for trend). In post hoc analysis, 60-day mortality was lower in tolvaptan-treated patients with renal dysfunction or severe systemic congestion.. Tolvaptan administered in addition to standard therapy may hold promise for management of systemic congestion in patients hospitalized for heart failure.

Topics: Ambulatory Care; Antidiuretic Hormone Receptor Antagonists; Benzazepines; Cardiovascular Agents; Diuretics; Double-Blind Method; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Tolvaptan; Ventricular Dysfunction, Left; Weight Loss

Topics: Adult; Aged; Cardiovascular Agents; Diastole; Drug Therapy, Combination; Drugs, Chinese Herbal; Female; Heart Failure; Humans; Injections; Male; Middle Aged; Phytotherapy; Systole; Ventricular Dysfunction, Left

The effects of cardiac resynchronization therapy (CRT) in patients with mildly symptomatic heart failure have not been fully elucidated.. The Multicenter InSync ICD Randomized Clinical Evaluation II (MIRACLE ICD II) was a randomized, double-blind, parallel-controlled clinical trial of CRT in NYHA class II heart failure patients on optimal medical therapy with a left ventricular (LV) ejection fraction < or =35%, a QRS > or =130 ms, and a class I indication for an ICD. One hundred eighty-six patients were randomized: 101 to the control group (ICD activated, CRT off) and 85 to the CRT group (ICD activated, CRT on). End points included peak VO2, VE/CO2, NYHA class, quality of life, 6-minute walk distance, LV volumes and ejection fraction, and composite clinical response. Compared with the control group at 6 months, no significant improvement was noted in peak VO2, yet there were significant improvements in ventricular remodeling indexes, specifically LV diastolic and systolic volumes (P=0.04 and P=0.01, respectively), and LV ejection fraction (P=0.02). CRT patients showed statistically significant improvement in VE/CO2 (P=0.01), NYHA class (P=0.05), and clinical composite response (P=0.01). No significant differences were noted in 6-minute walk distance or quality of life scores.. In patients with mild heart failure symptoms on optimal medical therapy with a wide QRS complex and an ICD indication, CRT did not alter exercise capacity but did result in significant improvement in cardiac structure and function and composite clinical response over 6 months.

Topics: Aged; Cardiovascular Agents; Defibrillators, Implantable; Disease Progression; Double-Blind Method; Electric Countershock; Electrocardiography; Exercise Test; Exercise Tolerance; Heart Conduction System; Heart Failure; Humans; Male; Middle Aged; Postoperative Complications; Survival Rate; Tachycardia, Ventricular; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Fibrillation; Ventricular Remodeling

To assess the prevalence of heart failure and asymptomatic left ventricular systolic dysfunction in the chronically paced population.. Three hundred and seven patients were identified from attendance at routine pacemaker follow-up clinic. Subjects underwent a medical history and examination, 6-minute walk test and echocardiography. 94 (31%) had a left ventricular ejection fraction (LVEF) <40%, of whom 83 had symptoms of heart failure (70% NYHA II, 26% NYHA III and 4% NYHA IV). Heart failure was more prevalent in patients with single chamber compared to dual chamber pacemakers, (DDD(R) 18% vs 35% VVI(R), p<0.008), and those with chronic atrial fibrillation (AF) compared to those with sinus rhythm (42% vs 21%, p=0.003). Decreasing 6-minute walk distance, history of ischaemic heart disease and years of pacing were independently associated with the presence of heart failure (combined R=0.572, p<0.001).. Heart failure due to left ventricular systolic dysfunction is common in the paced population. Only a minority of these had a pre-existing diagnosis and a smaller proportion were on 'optimal' therapy. Echocardiographic screening of this high-risk population is justified to improve rates of diagnosis and treatment of heart failure.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Blood Flow Velocity; Cardiac Output, Low; Cardiac Pacing, Artificial; Cardiovascular Agents; Diabetic Angiopathies; Double-Blind Method; Dyspnea; Echocardiography; Exercise Tolerance; Fatigue; Female; Humans; Male; Middle Aged; Risk Factors; Stroke Volume; Ventricular Dysfunction, Left

To assess antiischemic efficacy, safety and effect on myocardial perfusion of a course treatment with mildronate (as monotherapy and in combination with atenolol) in patients with postinfarction left ventricular dysfunction associated with moderate heart failure.. Patients (n=47) with postinfarction cardiosclerosis, angina, and decreased tolerance to physical exertion were divided into 2 groups. Patients of group 1 had functional class II angina and NYHA class I-II heart failure, patients of group 2 had functional class II-III angina and severe heart failure. Mildronate (0.75-1.0 g/day) was used as monotherapy in group 1 and in combination with atenolol (25-50 mg/day) in group 2. Duration of therapy was 3 weeks.. The use of mildronate was associated with marked antiischemic effect. Combined administration of mildronate and atenolol resulted in additional antiischemic effect without impairment of hemodynamics in patients with severe heart failure. Course use of mildronate was well tolerated. Adverse effects were registered in 4,2% of cases.

Topics: Adrenergic beta-Antagonists; Atenolol; Cardiovascular Agents; Drug Therapy, Combination; Humans; Male; Methylhydrazines; Middle Aged; Mitochondrial Trifunctional Protein; Multienzyme Complexes; Myocardial Infarction; Ventricular Dysfunction, Left

Implantable cardioverter defibrillator (ICD) therapy with backup ventricular pacing increases survival in patients with life-threatening ventricular arrhythmias. Most currently implanted ICD devices provide dual-chamber pacing therapy. The most common comorbid cause for mortality in this population is congestive heart failure.. To determine the efficacy of dual-chamber pacing compared with backup ventricular pacing in patients with standard indications for ICD implantation but without indications for antibradycardia pacing.. The Dual Chamber and VVI Implantable Defibrillator (DAVID) Trial, a single-blind, parallel-group, randomized clinical trial.. A total of 506 patients with indications for ICD therapy were enrolled between October 2000 and September 2002 at 37 US centers. All patients had a left ventricular ejection fraction (LVEF) of 40% or less, no indication for antibradycardia pacemaker therapy, and no persistent atrial arrhythmias.. All patients had an ICD with dual-chamber, rate-responsive pacing capability implanted. Patients were randomly assigned to have the ICDs programmed to ventricular backup pacing at 40/min (VVI-40; n = 256) or dual-chamber rate-responsive pacing at 70/min (DDDR-70; n = 250). Maximal tolerated medical therapy for left ventricular dysfunction, including angiotensin-converting enzyme inhibitors and beta-blockers, was prescribed to all patients.. Composite end point of time to death or first hospitalization for congestive heart failure.. One-year survival free of the composite end point was 83.9% for patients treated with VVI-40 compared with 73.3% for patients treated with DDDR-70 (relative hazard, 1.61; 95% confidence interval [CI], 1.06-2.44). The components of the composite end point, mortality of 6.5% for VVI-40 vs 10.1% for DDDR-70 (relative hazard, 1.61; 95% CI, 0.84-3.09) and hospitalization for congestive heart failure of 13.3% for VVI-40 vs 22.6% for DDDR-70 (relative hazard, 1.54; 95% CI, 0.97-2.46), also trended in favor of VVI-40 programming.. For patients with standard indications for ICD therapy, no indication for cardiac pacing, and an LVEF of 40% or less, dual-chamber pacing offers no clinical advantage over ventricular backup pacing and may be detrimental by increasing the combined end point of death or hospitalization for heart failure.

Topics: Adrenergic beta-Antagonists; Aged; Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anticoagulants; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Cardiovascular Agents; Catheter Ablation; Defibrillators, Implantable; Digoxin; Diuretics; Female; Heart Failure; Humans; Male; Middle Aged; Pacemaker, Artificial; Single-Blind Method; Survival Analysis; Tachycardia, Ventricular; Ventricular Dysfunction, Left; Warfarin

This study was conducted to evaluate willingness to prescribe medication based on identical data presented in different outcome terms to health professionals of varied discipline, geographic location, and level of training. Cross-sectional survey using a self-administered questionnaire was performed in 400 health professionals (physicians, pharmacists, physicians-in-training, and pharmacy students) in the United States and Europe. Data reflecting a clinical trial were presented in 6 outcome terms: 3 terms describing identical mortality (relative risk reduction, absolute risk reduction, and number of patients needed to be treated to prevent 1 death); and 3 distractors (increased life expectancy, decreased hospitalization rate, and decreased cost). Willingness to prescribe and rank order of medication preference assuming willingness to prescribe were measured. The results of the study showed that willingness to prescribe and first choice preference were significantly greater when study results were presented as relative risk reduction than when identical mortality data were presented as absolute risk reduction or number of patients needed to be treated to avoid 1 death (p <0.001). Increase in life expectancy was the most influential distractor. In conclusion, this study, performed in the era of "evidence-based medicine," demonstrates that the method of reporting research trial results has significant influence on health professionals' willingness to prescribe. The high numerical value of relative risk reduction and the concrete and tangible quality of increased life expectancy exert greater influence on health professionals than other standard outcome terms.

Topics: Cardiovascular Agents; Clinical Trials as Topic; Cross-Sectional Studies; Drug Prescriptions; Drug Utilization; Europe; Evidence-Based Medicine; Humans; Practice Patterns, Physicians'; Surveys and Questionnaires; United States; Ventricular Dysfunction, Left

In order to better explore the toxicity and the activity of high dose epirubicin (120 mg/m2, 3 weeks) we analyzed a population of 127 metastatic breast cancer patients, treated in a randomized clinical trial conducted to evaluate the cardioprotective effect of dexrazoxane against epirubicin induced cardiotoxicity. All the patients had a diagnosis of metastatic breast cancer, an ECOG performance status < or = 2 and normal hematologic, renal, hepatic and cardiac function. No prior adjuvant chemotherapy including anthracycline was allowed. Epirubicin was given at the dose of 120 mg/m2 i.v. bolus every 3 weeks. One hundred twenty five patients were evaluable for toxicity and response. Seventeen patients (11%) had a complete response and 47 patients (37%) a partial response, for an overall response rate of 48%. The median progression free and overall survivals were 8.3 months and 18.3 months, respectively. Grade 3 and 4 leukopenia were observed in 8% and 7% of the patients, respectively. The most frequent nonhematological grade 3 toxicities were alopecia (87%), nausea and vomiting (16%), and mucositis (8%). Cardiotoxicity, defined as occurrence of congestive heart failure, decrease in resting left ventricular ejection fraction (L-VEF) to < or = 45%, or 20 EF units decrease from baseline L-VEF, was observed in 19% of the patients, after a median cumulative dose of epirubicin of 720 mg/m2 (range 120-1440). This study confirms in a large series of patients the activity of high dose epirubicin; however, the high incidence of cardiotoxicity requires a careful evaluation of cardiac risk factors before treatment.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Breast Neoplasms; Cardiovascular Agents; Epirubicin; Female; Heart Failure; Humans; Injections, Intravenous; Middle Aged; Razoxane; Treatment Outcome; Ventricular Dysfunction, Left

Previous studies have suggested suboptimal use of cardiac medications for secondary prevention after myocardial infarction (MI) and atrial fibrillation (AF), especially among older people.. To determine whether patients older than 75 years are less likely than those aged 65 to 74 to be prescribed medications with evidence-based indications, including angiotensin-converting enzyme (ACE) inhibitors for left ventricular dysfunction (LVD) and/or diabetes mellitus (DM), aspirin and/or beta-blockers for those with a history of MI, and warfarin for chronic AF.. A retrospective cohort study.. Twenty-nine hospitals, predominantly tertiary-care institutions.. A total of 407 patients randomized to ventricular or dual-chamber pacing from February 26, 1993, to September 30, 1994, in the Pacemaker Selection in the Elderly (PASE) trial.. A review of the patient's medical history and a physical exam at study enrollment, three follow-up timepoints, and a study closeout.. Patients older than 75 years with LVD and/or DM were less likely to be prescribed ACE inhibitors (OR = .56 (0.31-1.00)); patients older than 75 with a history of MI were less likely to be taking aspirin (OR = .43 (0.19-.95)), and patients older than 75 with AF were less likely to be prescribed warfarin (OR = .18 (0.05-.61)). Patients older than 75 years of age with any or all of the conditions studied were less likely to be prescribed indicated medications than those ages 65 to 74 (OR = .35 (0.18-.70)), after controlling for between-group differences in comorbidity, gender, and number of noncardiac medications.. Older age is a significant independent negative correlate of evidence-based cardiac medication use in this cohort. Causes for this finding need to be explored.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Cardiovascular Agents; Combined Modality Therapy; Comorbidity; Diabetes Mellitus; Drug Therapy, Combination; Drug Utilization; Female; Frail Elderly; Humans; Male; Myocardial Infarction; Pacemaker, Artificial; Retrospective Studies; Single-Blind Method; Ventricular Dysfunction, Left

Topics: Acute Disease; Bisoprolol; Cardiomegaly; Cardiomyopathies; Cardiovascular Agents; Echocardiography; Genetic Testing; Heart Failure; Humans; Loeys-Dietz Syndrome; Losartan; Male; Middle Aged; Mutation; Pulmonary Edema; Receptor, Transforming Growth Factor-beta Type I; Spironolactone; Treatment Outcome; Ventricular Dysfunction, Left

Topics: Acyclic Monoterpenes; Aldehydes; Animals; Cardiovascular Agents; Diabetic Cardiomyopathies; Fibrosis; Heart Failure; Male; Rats, Sprague-Dawley; Vascular Endothelial Growth Factor Receptor-1; Ventricular Dysfunction, Left

Topics: Cardiovascular Agents; Eligibility Determination; Heart Failure; Humans; India; Interrupted Time Series Analysis; Prospective Studies; Stroke Volume; Ventricular Dysfunction, Left

Many studies have shown the beneficial effects of aconite water-soluble alkaloid extract (AWA) in experimental models of heart disease, which have been ascribed to the presence of aconine, hypaconine, talatisamine, fuziline, neoline, and songorine. This study evaluated the effects of a chemically characterized AWA by chemical content, evaluated its effects in suprarenal abdominal aortic coarctation surgery (AAC)-induced chronic heart failure (CHF) in rats, and revealed the underlying mechanisms of action by proteomics.. Rats were distributed into different groups: sham, model, and AWA-treated groups (10, 20, and 40 mg/kg/day). Sham rats received surgery without AAC, whereas model rats an AWA-treated groups underwent AAC surgery. after 8 weeks, the treatment group was fed AWA for 4 weeks, and body weight was assessed weekly. At the end of the treatment, heart function was tested by echocardiography. AAC-induced chronic heart failure, including myocardial fibrosis, cardiomyocyte hypertrophy, and apoptosis, was evaluated in heart tissue and plasma by RT-qPCR, ELISA, hematoxylin and eosin (H&E) staining, Masson's trichrome staining, TUNEL staining, and immunofluorescence staining of α-SMA, Col Ⅰ, and Col Ⅲ. Then, a proteomics approach was used to explore the underlying mechanisms of action of AWA in chronic heart failure.. AWA administration reduced body weight gain, myocardial fibrosis, cardiomyocyte hypertrophy, and apoptosis, and rats showed improvement in cardiac function compared to model group. The extract significantly ameliorated the AAC-induced altered expression of heart failure markers such as ANP, NT-proBNP, and β-MHC, as well as fibrosis, hypertrophy markers MMP-2 and MMP-9, and other heart failure-related factors including plasma levels of TNF-α and IL-6. Furthermore, the extract reduced the protein expression of α-SMA, Col Ⅰ, and Col Ⅲ in the left ventricular (LV), thus inhibiting the LV remodeling associated with CHF. In addition, proteomics characterization of differentially expressed proteins showed that AWA administration inhibited left ventricular remodeling in CHF rats via a calcium signaling pathway, and reversed the expression of RyR2 and SERCA2a.. AWA extract exerts beneficial effects in an AAC-induced CHF model in rats, which was associated with an improvement in LV function, hypertrophy, fibrosis, and apoptotic status. These effects may be related to the regulation of calcium signaling by the altered expression of RyR2 and SERCA2a.

Topics: Aconitum; Animals; Apoptosis; Calcium Signaling; Cardiovascular Agents; Chronic Disease; Disease Models, Animal; Fibrosis; Heart Failure; Hypertrophy, Left Ventricular; Myocytes, Cardiac; Plant Extracts; Rats, Sprague-Dawley; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Solubility; Solvents; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling; Water

Cancer associated thrombosis is recognized. However, pulmonary embolism (PE) from testicular cancer is rarely reported. Right ventricular (RV) function and PE are closely related. The RV cannot cope with a sudden increase in afterload because of PE and this causes dysfunction, but isolated left ventricular dysfunction in this context is not reported in the literature.. We report an unusual association of pulmonary embolism and testicular germ cell tumor complicating severe left heart failure and full recovery at three months follow up in a 33-year-old patient with no prior medical history. The diagnosis was made after comprehensive history taking and physical examination with the help of different imaging modalities. Full recovery was achieved after optimal medical therapy.. This case raises our awareness of unusual clinical presentation as we report associated left-sided severe heart failure in cancer-related pulmonary embolism. Pulmonary embolism in healthy young adults warrant in-depth causative exploration.

Topics: Adult; Anticoagulants; Cardiovascular Agents; Heart Failure; Humans; Male; Neoplasms, Germ Cell and Embryonal; Orchiectomy; Pulmonary Embolism; Recovery of Function; Testicular Neoplasms; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Aneurysm, False; Bisoprolol; Cardiovascular Agents; Catheter Ablation; Female; Heart Ventricles; Humans; Middle Aged; Tachycardia, Ventricular; Ventricular Dysfunction, Left

Topics: Action Potentials; Cardiomyopathies; Cardiovascular Agents; Defibrillators, Implantable; Electric Countershock; Electrocardiography; Female; Heart Rate; Humans; Immunosuppressive Agents; Middle Aged; Tachycardia, Supraventricular; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Vepoloxamer (VEPO), a rheologic agent, repairs damaged cell membranes, thus inhibiting unregulated Ca. Thirty-five HF dogs were studied. Study 1: 21 of 35 dogs were randomized to 2-h infusion of VEPO at dose of 450 mg/kg (n = 7) or VEPO at 225 mg/kg (n = 7) or normal saline (control, n = 7). Hemodynamics were measured at 2 h, 24 h, 1 week, and 2 weeks after infusion. Study 2: 14 HF dogs were randomized to 2-h infusions of VEPO (450 mg/kg, n = 7) or normal saline (control, n = 7). Each dog received 2 infusions of VEPO or saline (pulsed therapy) 3 weeks apart and hemodynamics measured at 24 h, and 1, 2, and 3 weeks after each infusion. In both studies, the change between pre-infusion measures and measures at other time points (treatment effect, Δ) was calculated.. Study 1: compared to pre-infusion, high dose VEPO increased LVEF by 11 ± 2% at 2 h, 8 ± 2% at 24 h (p < 0.05), 8 ± 2% at 1 week (p < 0.05), and 4 ± 2% at 2 weeks. LV EF also increased with low-dose VEPO but not with saline. Study 2: VEPO but not saline significantly increased LVEF by 6.0 ± 0.7% at 2 h (p < 0.05); 7.0 ± 0.7%% at 1 week (p < 0.05); 1.0 ± 0.6% at 3 weeks; 6.0 ± 1.3% at 4 weeks (p < 0.05); and 5.9 ± 1.3% at 6 weeks (p < 0.05).. Intravenous VEPO improves LV function for at least 1 week after infusion. The benefits can be extended with pulsed VEPO therapy. The results support development of VEPO for treating patients with acute on chronic HF.

Topics: Animals; Calcium Signaling; Cardiovascular Agents; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Heart Failure; Infusions, Intravenous; Poloxamer; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

The study aimed to investigate the effects of the sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin on chronic heart failure (HF) in normoglycemic rats. The effects of empagliflozin were compared with the standard medications for HF, e.g., angiotensin-converting enzyme (ACE) inhibitor fosinopril, beta-blocker bisoprolol, and aldosterone antagonist spironolactone. Myocardial infarction (MI) was induced in male Wistar rats via permanent ligation of the left descending coronary artery. One-month post MI, 50 animals were randomized into 5 groups (n = 10): vehicle-treated, empagliflozin (1.0 mg/kg), fosinopril (10 mg/kg), bisoprolol (10 mg/kg), and spironolactone (20 mg/kg). All medications except empagliflozin were titrated within a month and administered per os daily for 3 months. Echocardiography, 24-hour urine volume test, and treadmill exercise tests were performed at the beginning and at the end of the study. Treatment with empagliflozin slowed the progression of left ventricular dysfunction: LV sizes and ejection fraction were not changed and the minute volume was significantly increased (from 52.0 ± 15.5 to 61.2 ± 21.2 ml/min) as compared with baseline. No deaths occurred in empagliflozin group. The 24-hour urine volume tends to be higher in empagliflozin and spironolactone groups than in vehicle and fosinopril group. Moreover, empagliflozin exhibited maximal physical exercise tolerance in comparison with all investigated groups (289 ± 27 s versus 183 ± 61 s in fosinopril group, 197 ± 95 s in bisoprolol group, and 47 ± 46 s in spironolactone group, p = 0.0035 for multiple comparisons). Sodium-glucose co-transporter 2 inhibitor empagliflozin reduced progression of left ventricular dysfunction and improved tolerance of physical exercise in normoglycemic rats with HF. Empagliflozin treatment was superior with respect to physical tolerance compared with fosinopril, bisoprolol, and spironolactone.

Topics: Animals; Benzhydryl Compounds; Bisoprolol; Cardiovascular Agents; Chronic Disease; Disease Models, Animal; Exercise Tolerance; Fosinopril; Glucosides; Heart Failure; Male; Myocardial Infarction; Rats, Wistar; Sodium-Glucose Transporter 2 Inhibitors; Spironolactone; Ventricular Dysfunction, Left; Ventricular Function, Left

HFpEF (heart failure with preserved ejection fraction) is a major consequence of diabetic cardiomyopathy with no effective treatments. Here, we have characterized Akita mice as a preclinical model of HFpEF and used it to confirm the therapeutic efficacy of the mitochondria-targeted dicarbonyl scavenger, MitoGamide.. A longitudinal echocardiographic analysis confirmed that Akita mice develop diastolic dysfunction with reduced E peak velocity, E/A ratio and extended isovolumetric relaxation time (IVRT), while the systolic function remains comparable with wild-type mice. The myocardium of Akita mice had a decreased ATP/ADP ratio, elevated mitochondrial oxidative stress and increased organelle density, compared with that of wild-type mice. MitoGamide, a mitochondria-targeted 1,2-dicarbonyl scavenger, exhibited good stability in vivo, uptake into cells and mitochondria and reactivity with dicarbonyls. Treatment of Akita mice with MitoGamide for 12 weeks significantly improved the E/A ratio compared with the vehicle-treated group.. Our work confirms that the Akita mouse model of diabetes replicates key clinical features of diabetic HFpEF, including cardiac and mitochondrial dysfunction. Furthermore, in this independent study, MitoGamide treatment improved diastolic function in Akita mice.

Topics: Animals; Benzamides; Cardiovascular Agents; Diabetic Cardiomyopathies; Disease Models, Animal; Glycation End Products, Advanced; Heart Failure; Male; Mice, Inbred C57BL; Mice, Mutant Strains; Mitochondria, Heart; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Aged; Cardiovascular Agents; Carvedilol; Drug Hypersensitivity Syndrome; Female; Humans; New Zealand; Ventricular Dysfunction, Left

This study aimed to investigate the effects and molecular mechanisms of ivabradine in preventing cardiac hypertrophy in an established transverse aortic constriction (TAC) mouse model. A total of 56 male C57BL/6 mice were randomly assigned into the following seven groups (8 mice per group): sham, TAC model, Iva-10 (10 mg/kg/day ivabradine), Iva-20 (20 mg/kg/day ivabradine), Iva-40 (40 mg/kg/day ivabradine), Iva-80 (80 mg/kg/day ivabradine), and Rap (rapamycin, a positive control). Echocardiography and left ventricular hemodynamics were performed. Hematoxylin-eosin (H&E), Masson's trichome staining, and TUNEL assays were conducted to evaluate cardiac hypertrophy, fibrosis, and apoptosis, respectively. Western blotting was performed to detect the expression of proteins related to the PI3K/Akt/mTOR/p70S6K pathway. Ivabradine could effectively improve left ventricular dysfunction and hypertrophy induced by TAC in a dose-independent manner. Moreover, no obvious change in heart rate (HR) was observed in the TAC and Rap groups, whereas a significant decrease in HR was found after ivabradine treatment (P < 0.05). Cardiac hypertrophy, fibrosis, and apoptosis induced by TAC were notably suppressed after either rapamycin or ivabradine treatment (P < 0.05). Ivabradine and rapamycin also decreased the expression of PI3K/Akt and mTOR induced by TAC. Ivabradine improved cardiac hypertrophy and fibrosis as well as reduced cardiomyocyte apoptosis via the PI3K/Akt/mTOR/p70S6K pathway in TAC model mice.

Topics: Animals; Aortic Diseases; Apoptosis; Cardiovascular Agents; Constriction, Pathologic; Disease Models, Animal; Hypertrophy, Left Ventricular; Ivabradine; Male; Mice; Mice, Inbred C57BL; Myocytes, Cardiac; Pressure; Ventricular Dysfunction, Left

Left ventricular (LV) dysfunction due to anthracycline-induced cardiotoxicity (AIC) has been believed to be irreversible. However, this has not been confirmed and standard medical treatment for heart failure (HF) including renin-angiotensin inhibitors and β-blockers may lead to its recovery.. We thus retrospectively studied 350 cancer patients receiving anthracycline-based chemotherapy from 2001 to 2015 in our institution. Fifty-two patients (14.9%) developed AIC with a decrease in LV ejection fraction (LVEF) of 24.1% at a median time of 6 months [interquartile range (IQR) 4-22 months] after anthracycline therapy. By multivariate analysis, AIC was independently associated with cardiac comorbidities including ischemic heart disease, valvular heart disease, arrhythmia, and cardiomyopathy [odds ratio (OR) 6.00; 95% confidence interval (CI) 2.27-15.84, P = 0.00044), lower baseline LVEF (OR per 1% 1.09; 95% CI 1.04-1.14, P = 0.00034). During the median follow-up of 3.2 years, LV systolic dysfunction recovered among 33 patients (67.3%) with a median time of 4 months (IQR 2-6 months), which was independently associated with the introduction of standard medical treatment for HF (OR 9.39; 95% CI 2.27-52.9, P = 0.0014) by multivariate analysis.. Early initiation of standard medical treatment for HF may lead to LV functional recovery in AIC.

Topics: Adult; Aged; Anthracyclines; Antibiotics, Antineoplastic; Cardiotoxicity; Cardiovascular Agents; Female; Heart Failure; Humans; Male; Middle Aged; Neoplasms; Recovery of Function; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Recent studies reported that cAMP-binding protein Epac1-deficient mice were protected against various forms of cardiac stress, suggesting that pharmacological inhibition of Epac1 could be beneficial for the treatment of cardiac diseases. To test this assumption, we characterized an Epac1-selective inhibitory compound and investigated its potential cardioprotective properties.. We used the Epac1-BRET (bioluminescence resonance energy transfer) for searching for non-cyclic nucleotide Epac1 modulators. A thieno[2,3-b]pyridine derivative, designated as AM-001 was identified as a non-competitive inhibitor of Epac1. AM-001 has no antagonist effect on Epac2 or protein kinase A activity. This small molecule prevents the activation of the Epac1 downstream effector Rap1 in cultured cells, in response to the Epac1 preferential agonist, 8-CPT-AM. In addition, we found that AM-001 inhibited Epac1-dependent deleterious effects such as cardiomyocyte hypertrophy and death. Importantly, AM-001-mediated inhibition of Epac1 reduces infarct size after mouse myocardial ischaemia/reperfusion injury. Finally, AM-001 attenuates cardiac hypertrophy, inflammation and fibrosis, and improves cardiac function during chronic β-adrenergic receptor activation with isoprenaline (ISO) in mice. At the molecular level, ISO increased Epac1-G protein-coupled receptor kinase 5 (GRK5) interaction and induced GRK5 nuclear import and histone deacetylase type 5 (HDAC5) nuclear export to promote the activity of the prohypertrophic transcription factor, myocyte enhancer factor 2 (MEF2). Inversely, AM-001 prevented the non-canonical action of GRK5 on HDAC5 cytoplasmic shuttle to down-regulate MEF2 transcriptional activity.. Our study represents a 'proof-of-concept' for the therapeutic effectiveness of inhibiting Epac1 activity in cardiac disease using small-molecule pharmacotherapy.

Topics: Animals; Cardiovascular Agents; Cell Death; Chronic Disease; Disease Models, Animal; Fibrosis; G-Protein-Coupled Receptor Kinase 5; Guanine Nucleotide Exchange Factors; HEK293 Cells; Histone Deacetylases; Humans; MEF2 Transcription Factors; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Myocardial Infarction; Myocardial Reperfusion Injury; Myocytes, Cardiac; Rats; Signal Transduction; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Arrhythmic risk stratification is a challenging issue in patients with dilated cardiomyopathy (DCM), particularly when left ventricular ejection fraction (LVEF) is more than 35%. We studied the prevalence and predictors of sudden cardiac death or malignant ventricular arrhythmias (SCD/MVAs) in DCM patients categorized at low arrhythmic risk because of intermediate left ventricular dysfunction under optimal medical treatment (OMT).. DCM patients considered at low arrhythmic risk (LVEF >35% and New York Heart Association class I-III after 6 ± 3 months of OMT) were analysed. An arrhythmogenic profile was defined as the presence of at least one among a history of syncope, nonsustained ventricular tachycardia, at least 1000 premature ventricular contractions/24 h, at least 50 ventricular couplets/24 h at Holter ECG monitoring. SCD/MVAs was considered as the study end-point.. During a median follow-up of 152 months (interquartile range 100-234), 30 out of 360 (8.3%) patients at low arrhythmic risk (LVEF 47 ± 7%) experienced the study end-point [14 (3.9%) SCD and 16 (4.4%) MVA]. Compared with survivors, patients who experienced SCD/MVAs had more frequently an arrhythmogenic profile and a larger left atrium. Their LVEF at the last available evaluation before the arrhythmic event was 36 ± 12%. At multivariable analysis, left atrial end-systolic area [hazard ratio 1.107; 95% confidence interval (95% CI) 1.039-1.179, P = 0.002 for 1 mm increase] and arrhythmogenic profile (hazard ratio 3.667; 95% CI 1.762-7.632, P = 0.001) emerged as predictors of SCD/MVAs during follow-up.. A consistent quota of DCM patients with intermediate left ventricular dysfunction receiving OMT experienced SCD/MVA during follow-up. Left atrial dilatation and arrhythmogenic pattern were associated with a higher risk of SCD/MVA.

Topics: Adult; Arrhythmias, Cardiac; Cardiomyopathy, Dilated; Cardiovascular Agents; Death, Sudden, Cardiac; Female; Humans; Incidence; Italy; Male; Middle Aged; Prevalence; Prognosis; Registries; Retrospective Studies; Risk Assessment; Risk Factors; Stroke Volume; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left

Background The Heart Team ( HT ) comprises integrated interdisciplinary decision making. Current guidelines assign a Class Ic recommendation for an HT approach to complex coronary artery disease ( CAD ). However, there remains a paucity of data in regard to hard clinical end points. The aim was to determine characteristics and outcomes in patients with complex CAD following HT discussion. Methods and Results This observational study was conducted at St Thomas' Hospital (London, UK). Case mixture included unprotected left main, 2-vessel (including proximal left anterior descending artery) CAD , 3-vessel CAD , or anatomical and/or clinical equipoise. HT strategy was defined as optimal medical therapy ( OMT ) alone, OMT +percutaneous coronary intervention ( PCI ), or OMT +coronary artery bypass grafting. From April 2012 to 2013, 51 HT meetings were held and 398 cases were discussed. Patients tended to have multivessel CAD (74.1%), high SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) scores (median, 30; interquartile range, 23-39), and average age 69±11 years. Multinomial logistic regression analysis performed to determine variables associated with HT strategy demonstrated decreased likelihood of undergoing PCI compared with OMT in older patients with chronic kidney disease and peripheral vascular disease. The odds of undergoing coronary artery bypass grafting compared with OMT decreased in the presence of cardiogenic shock and left ventricular dysfunction and increased in younger patients with 3-vessel CAD . Three-year survival was 60.8% (84 of 137) in the OMT cohort, 84.3% (107 of 127) in the OMT + PCI cohort, and 90.2% in the OMT +coronary artery bypass grafting cohort (92 of 102). Conclusions In our experience, the HT approach involved a careful selection process resulting in appropriate patient-specific decision making and good long-term outcomes in patients with complex CAD .

Topics: Age Factors; Aged; Aged, 80 and over; Cardiology; Cardiovascular Agents; Clinical Decision-Making; Cooperative Behavior; Coronary Artery Bypass; Coronary Artery Disease; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Patient Care Team; Percutaneous Coronary Intervention; Prospective Studies; Severity of Illness Index; Shock, Cardiogenic; Survival Rate; Thoracic Surgery; United Kingdom; Ventricular Dysfunction, Left

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

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Drug Therapy, Combination; Heart Failure; Humans; Hypertrophy, Left Ventricular; Mineralocorticoid Receptor Antagonists; Recovery of Function; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Oxidative stress results in mtDNA damage and contributes to myocardial cell death. mtDNA repair enzymes are crucial for mtDNA repair and cell survival. We investigated a novel, mitochondria-targeted fusion protein (Exscien1-III) containing endonuclease III in myocardial ischemia-reperfusion injury and transverse aortic constriction (TAC)-induced heart failure. Male C57/BL6J mice (10-12 wk) were subjected to 45 min of myocardial ischemia and either 24 h or 4 wk of reperfusion. Exscien1-III (4 mg/kg ip) or vehicle was administered at the time of reperfusion. Male C57/BL6J mice were subjected to TAC, and Exscien1-III (4 mg/kg i.p) or vehicle was administered daily starting at 3 wk post-TAC and continued for 12 wk. Echocardiography was performed to assess left ventricular (LV) structure and function. Exscien1-III reduced myocardial infarct size ( P < 0.01) at 24 h of reperfusion and preserved LV ejection fraction at 4 wk postmyocardial ischemia. Exscien1-III attenuated TAC-induced LV dilation and dysfunction at 6-12 wk post-TAC ( P < 0.05). Exscien1-III reduced ( P < 0.05) cardiac hypertrophy and maladaptive remodeling after TAC. Assessment of cardiac mitochondria showed that Exscien1-III localized to mitochondria and increased mitochondrial antioxidant and reduced apoptotic markers. In conclusion, our results indicate that administration of Exscien1-III provides significant protection against myocardial ischemia and preserves myocardial structure and LV performance in the setting of heart failure. NEW & NOTEWORTHY Oxidative stress-induced mitochondrial DNA damage is a prominent feature in the pathogenesis of cardiovascular diseases. In the present study, we demonstrate the efficacy of a novel, mitochondria-targeted fusion protein that traffics endonuclease III specifically for mitochondrial DNA repair in two well-characterized murine models of cardiac injury and failure.

Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; Cardiovascular Agents; Disease Models, Animal; DNA Damage; DNA, Mitochondrial; Fibrosis; Heart Failure; Hypertrophy, Left Ventricular; Male; Mice, Inbred C57BL; Mitochondria, Heart; Myocytes, Cardiac; Oxidative Stress; Recombinant Fusion Proteins; Signal Transduction; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Left ventricular (LV) dysfunction develops during LV hypertrophy and particularly during tachycardia. Thus we investigated the effects of heart rate (HR) reduction with ivabradine, an I. Eight chronically instrumented pigs receiving continuous angiotensin II infusion during 28days to induce chronic hypertension and LV hypertrophy. Measurements were performed at Days 0 and 28 after stopping angiotensin II infusion in the presence and absence of ivabradine.. At Day 0, reducing HR from 75±3 to 55±2beats/min with ivabradine did not affect LV twist but slowed LV untwist along with an increase in LV end-diastolic pressure. At Day 28, LV posterior and septal wall thickness as well as the estimated LV mass increased, indicating LV hypertrophy. LV twist and untwist were significantly reduced by 33±4% from 16±1° and 32±6% from -154±9°/s, respectively, showing global LV systolic and diastolic dysfunction. In this context, ivabradine decreased HR by 25% from 86±5beats/min and significantly improved LV twist from 11±1 to 14±1° and LV untwist from -104±8 to -146±5°/s.. Administration of ivabradine during chronic hypertension and LV hypertrophy improved LV twist and untwist. This further supports the beneficial effect of this drug on both LV systolic and diastolic function during the development of LV hypertrophy.

Topics: Animals; Benzazepines; Cardiovascular Agents; Chronic Disease; Female; Hypertension; Hypertrophy, Left Ventricular; Ivabradine; Swine; Ventricular Dysfunction, Left

The molecular mechanisms through which ghrelin exerts its cardioprotective effects during cardiac remodeling post-myocardial infarction (MI) are poorly understood. The aim of this study was to investigate whether the cardioprotection mechanisms are mediated by modulation of JAK/STAT signaling and what triggers this modulation. Rats were divided into six groups (n = 12/group): control, sham, sham + ghrelin (100 µg/kg, s.c., daily, starting 1 day post-MI), MI, MI+ ghrelin, and MI+ ghrelin+ AG490, a potent JAK2 inhibitor (5 mg/kg, i.p., daily). All treatments were administered for 3 weeks. Administration of ghrelin to MI rats improved left ventricle (LV) architecture and restored cardiac contraction. In remote non-infarcted areas of MI rats, ghrelin reduced cardiac inflammation and lipid peroxidation and enhanced antioxidant enzymatic activity. In addition, independent of the growth factor/insulin growth factor-1 (GF/IGF-1) axis, ghrelin significantly increased the phosphorylation of JAK2 and Tyr702 and Ser727 residues of STAT3 and inhibited the phosphorylation of JAK1 and Tyr701 and Ser727 residues of STAT1, simultaneously increasing the expression of BCL-2 and decreasing in the expression of BAX, cleaved CASP3, and FAS. This effect coincided with decreased expression of SOCS3. All these beneficial effects of ghrelin, except its inhibitory action on IL-6 expression, were partially and significantly abolished by the co-administration of AG490. In conclusion, the cardioprotective effect of ghrelin against MI-induced LV injury is exerted via activation of JAK2/STAT3 signaling and inhibition of STAT1 signaling. These effects were independent of the GF/IGF-1 axis and could be partially mediated via inhibition of cardiac IL-6.

Topics: Animals; Apoptosis; Cardiovascular Agents; Disease Models, Animal; Ghrelin; Heart Ventricles; Interleukin-6; Janus Kinase 2; Male; Myocardial Infarction; Myocytes, Cardiac; Oxidative Stress; Rats, Sprague-Dawley; Signal Transduction; STAT1 Transcription Factor; STAT3 Transcription Factor; Suppressor of Cytokine Signaling 3 Protein; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Peripartum cardiomyopathy (PPCM) is a left ventricular systolic dysfunction failure emerges during the antepartum or puerperal period, and can result in maternal death. Reported incidences are increasing and differing globally. Echocardiography is the cornerstone for the diagnosis. The immediate goals in acute management are the stabilization of the hemodynamic state, providing symptomatic relief, and ensuring fetal wellbeing. Emergency physicians should be aware of PPCM at the differential diagnosis of dyspnea in pregnancy related emergencies and play role in early diagnosis.

Topics: Adrenergic beta-1 Receptor Antagonists; Adult; Anticoagulants; Cardiomyopathies; Cardiovascular Agents; Chest Pain; Drug Therapy, Combination; Dyspnea; Echocardiography; Emergency Service, Hospital; Female; Hemodynamics; Humans; Metoprolol; Puerperal Disorders; Radiography; Ventricular Dysfunction, Left

Left ventricular ejection fraction (LVEF) has shown to predict outcomes in patients with heart failure (HF). Left ventricular recovery (LVR) has shown to improve prognosis.. Guideline-directed medical therapy will predict LVR in patients with HF and reduced LVEF.. We studied 244 patients with newly diagnosed HF and an LVEF ≤35%. LVR was defined as an increase in LVEF ≥40%. Patients who experienced LVR were compared with those who had persistent left ventricular dysfunction.. Population characteristics included ischemic etiology, 38.1%; baseline LVEF, 23% ±6%; and mean baseline heart rate (HR), 75 ±13 bpm. Guideline-directed medical therapy was achieved as follows: angiotensin-converting enzyme inhibitors, 74.3%; β-blockers (BB), 95.4%; target dosing of angiotensin-converting enzyme inhibitors, 33.7%; target dosing of BB, 40.2%. LVR occurred in 154/244 patients (63.1%). By multivariable analysis, baseline HR ≤70 bpm was the only independent predictor of LVR (odds ratio: 3.39, 95% confidence interval: 1.5-7.5, P = 0.003). Target dosing of BB therapy was predictive of LVR only in the univariate analysis (odds ratio: 1.9, 95% confidence interval: 1.1-3.4, P = 0.03). Furthermore, the composite endpoint of HF hospitalization or mortality occurred less frequently in those who did vs those who did not achieve target BB doses (5.4% vs 16.7%, respectively; P = 0.023).. The novel findings of our analysis reveal that the only predictor of LVR in this study was a low baseline HR. Early modulation of HR in newly diagnosed HF patients may increase the rates of LVR.

Topics: Cardiovascular Agents; Chi-Square Distribution; Disease Progression; Heart Failure; Heart Rate; Hospitalization; Humans; Kaplan-Meier Estimate; Logistic Models; Multivariate Analysis; Odds Ratio; Recovery of Function; Retrospective Studies; Risk Factors; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Heart failure is a common adverse effect associated with doxorubicin treatment. The aim of this study is to investigate the effect of ivabradine treatment on doxorubicin-induced heart failure in conscious rats. Rats were treated with doxorubicin (2.5 mg/kg/d) or ivabradine (10 mg/kg/d) alone or along with doxorubicin injections. Changes in heart rate variability (HRV), baroreflex sensitivity, left ventricular (LV) function, serum cardiac troponin T, and cardiac histological features were taken as index parameters for the development of heart failure. Ivabradine significantly reduced the elevated heart rate; normalized the parameters of LV function, dP/dtmax and the relaxation time constant (Tau); reduced the elevated serum level of cardiac troponin T; and minimized the cardiac structural abnormalities in doxorubicin-treated rats. Moreover, ivabradine significantly increased the diminished time domain parameters of HRV, SDNN and rMSSD, and decreased the elevated low frequency power and the low frequency/high frequency while having no effect on the reduced high frequency power. Consistently, ivabradine significantly lowered the elevated baroreflex sensitivity measured by sodium nitroprusside. In conclusion, ivabradine ameliorated the LV dysfunction induced by doxorubicin. Moreover, ivabradine increased the overall HRV and restored the autonomic balance by reducing the sympathetic over activation. Therefore, ivabradine may have a possible therapeutic potential against doxorubicin-induced heart failure.

Topics: Animals; Arterial Pressure; Autonomic Nervous System; Autonomic Nervous System Diseases; Baroreflex; Cardiotoxicity; Cardiovascular Agents; Cardiovascular System; Disease Models, Animal; Doxorubicin; Heart Failure; Heart Rate; Ivabradine; Male; Rats, Wistar; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Pressure

Topics: Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Cardiovascular Agents; Catheter Ablation; Chronic Disease; Clinical Decision-Making; Heart Failure; Humans; Patient Selection; Randomized Controlled Trials as Topic; Recovery of Function; Recurrence; Research Design; Risk Assessment; Risk Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Anti-Arrhythmia Agents; Anticoagulants; Atrial Fibrillation; Cardiovascular Agents; Catheter Ablation; Chronic Disease; Clinical Decision-Making; Heart Failure; Humans; Patient Selection; Randomized Controlled Trials as Topic; Recovery of Function; Recurrence; Research Design; Risk Assessment; Risk Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Cardiovascular Agents; Clinical Decision-Making; Coronary Artery Bypass; Coronary Artery Disease; Humans; Patient Selection; Percutaneous Coronary Intervention; Risk Factors; Severity of Illness Index; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Patients developing cancer treatment-related left ventricular dysfunction (CTrLVD) require a prompt therapy. Hypotension, dizziness, and fatigue often limit the use of angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and β-blockers (BB) in cancer patients who may already be afflicted by these symptoms. Ivabradine is a heart rate-lowering drug that does not cause hypotension and may be used in heart failure with reduced left ventricular ejection fraction (LVEF).. The aim of this paper was to investigate the role of ivabradine to treat CTrLVD.. A retrospective analysis in a cohort of 30 patients with CTrLVD (LVEF < 50%) receiving ivabradine on top of the maximal tolerated dose of ACEi/ARB and BB was performed. We evaluated cardiovascular treatment, oncologic treatment, LVEF, functional class (New York Heart Association [NYHA]), and fatigue during the study period.. Ivabradine was initially started at the dose of 2.5 mg/b.i.d. in most patients and then carefully titrated. Hypotension (70%) and fatigue (77%) were the main causes limiting the treatment with ACEi/ARB and BB. After a mean follow-up of 6.5 months, LVEF increased from 45.1% (SD = 6.4) to 53.2% (SD = 3.9; p < 0.001). When patients were analyzed according to the type of cancer therapy, no difference in LVEF changes across the groups was found. NYHA class ameliorated in 11 patients, while fatigue improved in 8 patients. No serious cardiovascular side effects were reported.. The ability to improve symptoms and LVEF in unfit cancer patients makes ivabradine a reasonable pharmacological tool for treating CTrLVD.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anthracyclines; Cardiovascular Agents; Dose-Response Relationship, Drug; Fatigue; Female; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Neoplasms; Retrospective Studies; Trastuzumab; Ventricular Dysfunction, Left

Topics: Cardiac Pacing, Artificial; Cardiovascular Agents; Combined Modality Therapy; Coronary Restenosis; Heart Arrest; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Recurrence; ST Elevation Myocardial Infarction; Stents; Ventricular Dysfunction, Left; Ventricular Fibrillation; Ventricular Premature Complexes

Patients with coronary microvascular dysfunction (CMD) often have diastolic dysfunction, representing an important therapeutic target. Ranolazine-a late sodium current inhibitor-improves diastolic function in animal models and subjects with obstructive coronary artery disease (CAD).. We hypothesized that ranolazine would beneficially alter diastolic function in CMD.. To test this hypothesis, we performed retrospective tissue tracking analysis to evaluate systolic/diastolic strain, using cardiac magnetic resonance imaging cine images acquired in a recently completed, randomized, double-blind, placebo-controlled, crossover trial of short-term ranolazine in subjects with CMD and from 43 healthy reference controls.. Diastolic strain rate was impaired in CMD vs controls (circumferential diastolic strain rate: 99.9% ± 2.5%/s vs 120.1% ± 4.0%/s, P = 0.0003; radial diastolic strain rate: -199.5% ± 5.5%/s vs -243.1% ± 9.6%/s, P = 0.0008, case vs control). Moreover, peak systolic circumferential strain (CS) and radial strain (RS) were also impaired in cases vs controls (CS: -18.8% ± 0.3% vs -20.7% ± 0.3%; RS: 35.8% ± 0.7% vs 41.4% ± 0.9%; respectively; both P < 0.0001), despite similar and preserved ejection fraction. In contrast to our hypothesis, however, we observed no significant changes in left ventricular diastolic function in CMD cases after 2 weeks of ranolazine vs placebo.. The case-control comparison both confirms and extends our prior observations of diastolic dysfunction in CMD. That CMD cases were also found to have subclinical systolic dysfunction is a novel finding, highlighting the utility of this retrospective approach. In contrast to previous studies in obstructive CAD, ranolazine did not improve diastolic function in CMD.

Topics: Adult; Aged; Cardiovascular Agents; Clinical Trials as Topic; Coronary Artery Disease; Coronary Circulation; Coronary Vessels; Diastole; Female; Humans; Magnetic Resonance Imaging, Cine; Male; Microcirculation; Microvessels; Middle Aged; Myocardium; Ranolazine; Retrospective Studies; Sodium Channel Blockers; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Adult; Aged; Cardiomyopathy, Dilated; Cardiovascular Agents; Diastole; Disease Progression; Echocardiography, Doppler, Pulsed; Female; Heart Failure; Humans; Male; Middle Aged; Prospective Studies; Recovery of Function; Stroke Volume; Systole; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Hydralazine-nitrate combination is recommended for patients with heart failure with reduced ejection fraction (HFrEF)/systolic heart failure who are symptomatic despite guideline-directed medical therapy (GDMT). Use of nitrates alone for this indication is not well-established. This study aims to evaluate the effect of oral nitrates on all-cause mortality and hospitalization in HFrEF patients using GDMT.. Nitrate prescription at discharge and its association with all-cause mortality and heart failure hospitalization were examined in a propensity-matched analysis of 648 HFrEF patients followed for a median of 56 months. A total of 269 (42%) patients died during that period. In Cox regression analysis, nitrate usage was associated with a slightly increased mortality risk compared with not using nitrates (hazard ratio 1.29; 95% confidence interval 1.01-1.65; P = .040), which continued modestly after the propensity-matched analysis (hazard ratio  1.26; 95% confidence interval 0.95-1.68; P = .102). In both prematch and propensity-matched analyses, nitrate use was not associated with risk of rehospitalization. No significant effect was detected on subgroups stratified by coronary artery disease, age, gender, and background medical therapy.. In this study, oral nitrate use alone in addition to GDMT did not affect all-cause mortality and hospitalization risk in HFrEF patients during a long-term follow-up. There was even a modest tendency for increased risk of mortality.

Topics: Aged; Cardiovascular Agents; Female; Heart Failure; Hospitalization; Humans; Isosorbide Dinitrate; Male; Middle Aged; Mortality; Propensity Score; Retrospective Studies; Risk Factors; Stroke Volume; Survival Analysis; Turkey; Ventricular Dysfunction, Left

Patients with myocarditis and left ventricular (LV) dysfunction may improve after standard heart failure therapy. This improvement seems to be related to retreat of myocardial inflammation. The aim of the present study was to assess changes in clinical, echocardiographic and some laboratory parameters and to correlate them with changes in the number of inflammatory infiltrating cells in endomyocardial biopsy (EMB) samples during the 6-month follow-up, and to define predictors of LV function improvement among baseline parameters. Forty patients with biopsy-proven myocarditis and impaired LV function (LV ejection fraction-LVEF <40 %) with heart failure symptoms ≤ 6 months were evaluated. Myocarditis was defined as the presence of >14 mononuclear leukocytes/mm(2) and/or >7 T-lymphocytes/mm(2) in the baseline EMB. The EMB, echocardiography and clinical evaluation were repeated after 6 months of standard heart failure therapy. LVEF improved on average from 25 ± 9 to 42 ± 12 % (p < 0.001); LV end-systolic volume and LV end-diastolic volume (LVEDV) decreased from 158 ± 61 to 111 ± 58 ml and from 211 ± 69 to 178 ± 63 ml (both p < 0.001). NYHA class decreased from 2.6 ± 0.5 to 1.6 ± 0.6 (p < 0.001) and NTproBNP from 2892 ± 3227 to 851 ± 1835 µg/ml (p < 0.001). A decrease in the number of infiltrating leukocytes (CD45+/LCA+) from 23 ± 15 to 13 ± 8 cells/mm(2) and in the number of infiltrating T lymphocytes (CD3+) from 7 ± 5 to 4 ± 3 cells/mm(2) (both p < 0.001) was observed. The decline in the number of infiltrating CD45+ cells significantly correlated with the change in LVEF (R = -0.43; p = 0.006), LVEDV (R = 0.39; p = 0.012), NYHA classification (R = 0.35; p = 0.025), and NTproBNP (R = 0.33; p = 0.045). The decrease in the number of CD3+ cells correlated with the change of systolic and diastolic diameters of the left ventricle (R = -0.33; p = 0.038 and R = -0.45; p = 0.003) and with the change in LVEDV (R = -0.43; p = 0.006). Tricuspid annular plane systolic excursion (TAPSE) (OR 0.61; p = 0.005) and early transmitral diastolic flow velocity (E wave) (OR 0.89; p = 0.002) were identified as predictors of LVEF improvement. Improvements in clinical status, LV function and NTproBNP levels correlated with decrease in the number of infiltrating inflammatory cells. TAPSE and E wave velocity were significant predictors of improvement in multivariate regression. Our observations suggest that contemporary guidelines-based therapy of heart failure is an effective treatment

Topics: Adult; Biomarkers; Biopsy; Cardiomyopathies; Cardiovascular Agents; Chemotaxis, Leukocyte; Echocardiography, Doppler; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Predictive Value of Tests; Recovery of Function; Risk Factors; Stroke Volume; T-Lymphocytes; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Nitric oxide synthase uncoupling occurs under conditions of oxidative stress modifying the enzyme's function so it generates superoxide rather than nitric oxide. Nitric oxide synthase uncoupling occurs with chronic pressure overload, and both are ameliorated by exogenous tetrahydrobiopterin (BH4)-a cofactor required for normal nitric oxide synthase function-supporting a pathophysiological link. Genetically augmenting BH4 synthesis in endothelial cells fails to replicate this benefit, indicating that other cell types dominate the effects of exogenous BH4 administration. We tested whether the primary cellular target of BH4 is the cardiomyocyte or whether other novel mechanisms are invoked.. Mice with cardiomyocyte-specific overexpression of GTP cyclohydrolase 1 (mGCH1) and wild-type littermates underwent transverse aortic constriction. The mGCH1 mice had markedly increased myocardial BH4 and, unlike wild type, maintained nitric oxide synthase coupling after transverse aortic constriction; however, the transverse aortic constriction-induced abnormalities in cardiac morphology and function were similar in both groups. In contrast, exogenous BH4 supplementation improved transverse aortic constricted hearts in both groups, suppressed multiple inflammatory cytokines, and attenuated infiltration of inflammatory macrophages into the heart early after transverse aortic constriction.. BH4 protection against adverse remodeling in hypertrophic cardiac disease is not driven by its prevention of myocardial nitric oxide synthase uncoupling, as presumed previously. Instead, benefits from exogenous BH4 are mediated by a protective effect coupled to suppression of inflammatory pathways and myocardial macrophage infiltration.

Topics: Animals; Anti-Inflammatory Agents; Biopterins; Cardiovascular Agents; Cytokines; Cytoprotection; Disease Models, Animal; GTP Cyclohydrolase; Humans; Hypertrophy, Left Ventricular; Inflammation Mediators; Macrophages; Mice, Transgenic; Myocytes, Cardiac; Nitric Oxide; Nitric Oxide Synthase; Oxidation-Reduction; Signal Transduction; Superoxides; Time Factors; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

Heart rate (HR) reduction with ivabradine improves left ventricle filling by the prolongation of the diastolic time and increases stroke volume. But, it remains unclear what ivabradine's effect is on atrial conduction time and atrial mechanical functions. The aim of our study was to evaluate in stable outpatients with systolic heart failure (HF) the 3 months effect of ivabradine on atrial conduction time and mechanical functions.. We evaluated prospectively 43 (31 males, 12 females) patients with HF. Before and after treatment, all patients were evaluated by transthoracic M mode, two dimensional (2D), pulsed-wave (PW), continuous wave (CW), color flow and tissue Doppler imaging (TDI), and LA volumes were obtained apical four-chamber views by a disc's method. LA maximum volume (Vmax) at the end-systolic phase, LA minimum volume (Vmin) at the end-diastolic phase, and LA volume before atrial systole (Vp) were evaluated. The LA function parameters were calculated as follows: LA passive emptying volume = Vmax - Vp; LA passive emptying fraction = [(Vmax - Vp)/Vmax] × 100%, LA active emptying volume = Vp - Vmin; LA active emptying fraction = [(Vp - Vmin)/Vp] × 100%.. Thirty men and 13 women with mean ± SD age of 63.9 ± 10.1 years were included in this study. Resting heart rate was significantly reduced after ivabradine treatment. There were no significantly difference in LVEF, and E/A before and after ivabradine treatment. LA diameter and Vmin were similar before and after ivabradine treatment (p = 0.793 and p = 0.284). However, Vmax and Vp were significantly decreased after ivabradine treatment (p = 0.040 and p = 0.012). Moreover, LA active emptying volume and LA active emptying fraction were significantly decreased after ivabradine treatment (p = 0.030 and p = 0.008). The PA lateral, septal, and tricuspid durations were significantly reduced after ivabradine treatment (p < 0.001, p < 0.001, and p = 0.002, respectively). Interatrial electromechanical delay and right intra-atrial electromechanical delay were significantly decreased after ivabradine treatment (33.7 ± 12.7 vs 26.2 ± 10.1, p = 0.001; and 14.1 ± 6.1 vs 9.2 ± 6.8, p < 0.001).. The present study demonstrated that adding ivabradine to the standard therapy reduced HR and improves significantly LA electrical and mechanical functions in systolic HF patients.

Topics: Benzazepines; Cardiovascular Agents; Female; Heart Failure; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left

Everolimus drug-eluting stents (EES) are superior to early-generation drug-eluting stents (DES), releasing sirolimus (SES) or paclitaxel (PES) in preventing stent thrombosis (ST). Since an impaired LVEF seems to increase the risk of ST, we aimed to investigate the difference in outcome of patients with varying LVEF using EES versus early-generation DES.. In a prospective cohort study, we compared the risk of ST in patients in three LVEF subgroups: normal (LVEF >50%), mildly impaired (LVEF >40% and ≤50%) and moderate-severely impaired (LVEF ≤40%). Within these various LVEF groups, we compared EES with SES and PES after adjustment for baseline differences.. We assessed a cohort of 5363 patients, with follow-up of up to 4 years and available LVEF. Overall definite ST occurred in 123 (2.3%) patients. ST rates were higher in the LVEF moderate-severely impaired group compared with the normal LVEF group (2.8% vs 2.1%; HR 1.82; CI 1.10 to 3.00). Especially early ST (EST) was more frequent in the moderate-severely impaired LVEF group (HR 2.20; CI 1.06 to 4.53). Overall rates of definite ST were lower in patients using EES compared with patients using SES or PES in all LVEF groups. Interaction terms were not statistically significant. ST rates were higher in the moderate-severely impaired LVEF group compared with the normal LVEF group when using SES or PES, but not significantly different when using EES.. EES was associated with a lower risk of definite ST compared with early-generation DES. This lower risk was independent of LVEF, even though ST rates were higher in patients with a moderate-severely impaired LVEF.. MEC-2013-262.

Topics: Cardiovascular Agents; Coronary Artery Disease; Coronary Thrombosis; Drug-Eluting Stents; Everolimus; Humans; Incidence; Kaplan-Meier Estimate; Percutaneous Coronary Intervention; Proportional Hazards Models; Prospective Studies; Prosthesis Design; Registries; Risk Factors; Severity of Illness Index; Sirolimus; Stroke Volume; Switzerland; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Predicting the occurrence of aortic insufficiency (AI) during left ventricular assist device (LVAD) support has remained unsolved.. We enrolled 52 patients who had received continuous flow LVAD (14 axial and 38 centrifugal pumps) and who been followed for ≥6 months between Jun 2006 and Dec 2013. Native aortic valve (AV) opening was observed in 18 patients (35%) with improved LV systolic function, and none of them had AI. On multivariate logistic regression analysis preoperative shorter heart failure duration was the only independent predictor of postoperative native AV opening (P=0.042; odds ratio [OR], 0.999). Of the remaining 34 patients (65%) with closed AV, 11 had AI with enlargement of the aortic root and narrow pulse pressure. Among those with closed AV, axial pump use (n=13) was the only significant predictor of the development of AI (P=0.042; OR, 4.950). Patients with AI had lower exercise capacity and a higher readmission rate than those without AI during 2-year LVAD support (55% vs. 8%; P<0.001).. Native AV opening during LVAD support is profoundly associated with reversal of LV systolic function, especially in patients with preoperative shorter heart failure duration. Among those in whom the native AV remains closed, low pulsatility of axial flow pump may facilitate aortic root remodeling and post-LVAD AI development that results in worse clinical outcome.

Topics: Adult; Aortic Valve; Aortic Valve Insufficiency; Cardiovascular Agents; Combined Modality Therapy; Equipment Design; Female; Heart Failure; Heart Valves; Heart-Assist Devices; Hemodynamics; Humans; Male; Middle Aged; Postoperative Complications; Radiography; Retrospective Studies; Ultrasonography; Ventricular Dysfunction, Left

Difficulties initiating and uptitrating β-blockers due to tolerability can complicate management of heart failure. Among other actions, β-blockers reduce heart rate, which is an important cardiovascular risk factor in heart failure. A new therapeutic strategy is ivabradine, which reduces resting heart rate and is associated with improved outcomes.. A 5-month, prospective, open-label, nonrandomized single-center study was performed in 69 patients. All patients had chronic heart failure with left ventricular systolic dysfunction in sinus rhythm, each were initiated on 3.125 mg twice daily (bid) carvedilol alone (n = 36) or 3.125 mg bid carvedilol/5 mg bid ivabradine (n = 33), on top of background therapy including angiotensin-converting enzyme inhibitor (88%), diuretics (86%), antiplatelet agents (91%), and statins (90%). Dosages were uptitrated every 2 weeks to 25 mg bid carvedilol in both groups and 7.5 mg bid ivabradine maximum in the carvedilol/ivabradine group. Uptitration of carvedilol lasted 1.9 ± 0.4 months with carvedilol/ivabradine and 2.8 ± 0.6 months with carvedilol alone (P < 0.05).. The patients receiving ivabradine had lower resting heart rate at 5 months (61.6 ± 3.1 versus 70.2 ± 4.4 bpm, P < 0.05). Adding ivabradine to carvedilol in patients with heart failure was associated with increases in the 6-min walk test and ejection fraction (all P < 0.05). Treatment tolerability was satisfactory. Patients receiving ivabradine and carvedilol had lower heart rates and better exercise capacity than those on carvedilol alone.. Adding ivabradine to carvedilol in patients with chronic heart failure improves the uptitration of β-blocker. The results merit further verification in a prospective double-blind study.

Topics: Adrenergic beta-Antagonists; Aged; Benzazepines; Carbazoles; Cardiovascular Agents; Carvedilol; Drug Therapy, Combination; Exercise; Exercise Tolerance; Female; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Propanolamines; Prospective Studies; Risk Factors; Ventricular Dysfunction, Left

Topics: Adenoviridae Infections; Adult; Biopsy; Cardiovascular Agents; Combined Modality Therapy; Defibrillators; Disease Progression; Emergencies; Female; Fever; Heart-Assist Devices; Hemodynamics; Humans; Myocarditis; Myocardium; Parvoviridae Infections; Pericarditis; Shock, Cardiogenic; Spironolactone; Ventricular Dysfunction, Left

Topics: Ablation Techniques; Aged; Cardiac Resynchronization Therapy Devices; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Diagnosis, Differential; Disease Management; Echocardiography; Female; Heart Septum; Humans; Takotsubo Cardiomyopathy; Time; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Outflow Obstruction

Enhanced heart rate observed in metabolic syndrome (MS) contributes to the deterioration of left ventricular (LV) function via impaired LV filling and relaxation, increased myocardial O2 consumption, and reduced coronary perfusion. However, whether heart rate reduction (HRR) opposes LV dysfunction observed in MS is unknown.. We assessed in Zucker fa/fa rats, a rat model of MS, the cardiovascular effects of HRR induced by the If current inhibitor S38844 (3 mg · kg(-1) · d(-1)).. Delayed short-term (4 days) and long-term (90 days) HRR induced by S38844 reduced LV end-diastolic pressure and LV end-diastolic pressure-volume relation, increased myocardial tissue perfusion, decreased myocardial oxidized glutathione levels, and preserved cardiac output, without modifying LV end-systolic pressure and LV end-systolic pressure-volume relation, although only long-term S38844 opposed LV collagen accumulation. Long-term S38844 improved flow-induced endothelium-dependent dilatation of mesenteric arteries, while metabolic parameters, such as plasma glucose levels, and Hb1c, were never modified.. In rats with MS, HRR induced by the If inhibitor S38844 improved LV diastolic function and endothelium-dependent vascular dilatation, independent from modifications in metabolic status. Moreover, this improvement in cardiac function involves not only immediate effects such as improved myocardial perfusion and reduced oxidative stress but also long-term effects such as modifications in the myocardial structure.

Topics: Animals; Cardiovascular Agents; Diastole; Electrocardiography; Heart Rate; Heart Ventricles; Hemodynamics; Ion Channels; Male; Metabolic Syndrome; Oxidative Stress; Rats, Zucker; Ventricular Dysfunction, Left; Ventricular Function, Left

Through contemporary literature, the optimal strategy to manage coronary chronic total occlusions (CTOs) remains under debate.. The aim of the Italian Registry of Chronic Total Occlusions (IRCTO) was to provide data on prevalence, characteristics, and outcome of CTO patients according to the management strategy.. The IRCTO is a prospective real world multicentre registry enrolling patients showing at least one CTO. Clinical and angiographic data were collected independently from the therapeutic strategy [optimal medical therapy (MT), percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG)]; a comparative 1-year clinical follow-up was performed.. A total of 1777 patients were enrolled for an overall CTO prevalence of 13.3%. The adopted therapeutic strategies were as follows: MT in 826 patients (46.5%), PCI in 776 patients (43.7%), and CABG in the remaining 175 patients (9.8%). At 1-year follow-up, patients undergoing PCI showed lower rate of major adverse cardiac and cerebrovascular events (MACCE) (2.6% vs. 8.2% and vs. 6.9%; P < 0.001 and P < 0.01) and cardiac death (1.4% vs. 4.7% and vs. 6.3%; P < 0.001 and P < 0.001) in comparison with those treated with MT and CABG, respectively. After propensity score-matching analysis, patients treated with PCI showed lower incidence of cardiac death (1.5 vs. 4.4%; P < 0.001), acute myocardial infarction (1.1 vs. 2.9%; P = 0.03), and re-hospitalization (2.3 vs. 4.4% P = 0.04) in comparison with those managed by MT.. Our data showed how CTO PCI might significantly improve the survival and decrease MACCE occurrence at 1 year follow-up in comparison with MT and/or CABG.

Topics: Aged; Cardiovascular Agents; Chronic Disease; Coronary Angiography; Coronary Artery Bypass; Coronary Occlusion; Female; Humans; Italy; Male; Percutaneous Coronary Intervention; Prevalence; Prospective Studies; Registries; Treatment Outcome; Ventricular Dysfunction, Left

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

Patients with severe aortic stenosis (AS) and left ventricular systolic dysfunction pose a significant challenge to the managing physician. Conventional pharmacological therapy for systolic heart failure has not been proven beneficial in this setting. Ivabradine, a selective current inhibitor, decreases the spontaneous firing rate of sinoatrial nodal cells, thereby reducing the heart rate, and has been shown to reduce a composite end-point of heart failure hospitalization and mortality in patients with impaired left ventricular function. Herein are reported details of the hemodynamic effects and clinical outcome of ivabradine treatment in an 86-year-old man with severe AS and severe left ventricular systolic function.

Topics: Aged, 80 and over; Aortic Valve Stenosis; Benzazepines; Cardiac Catheterization; Cardiovascular Agents; Electrocardiography; Heart Failure, Systolic; Heart Rate; Heart Valve Prosthesis Implantation; Humans; Ivabradine; Male; Recovery of Function; Severity of Illness Index; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Algorithms; Cardiac Resynchronization Therapy; Cardiovascular Agents; Combined Modality Therapy; Defibrillators, Implantable; General Practice; Germany; Heart Failure; Humans; Monitoring, Ambulatory; Ventricular Dysfunction, Left

For multiple chemotherapeutics, cardiotoxicity is dose limiting and can lead to substantial morbidity and mortality. Early cardiac intervention has the potential to positively affect clinical course.. We reviewed 247 consecutive patients referred to the Stanford cardiology clinic for cancer therapy-associated cardiac abnormalities from 2004 to 2012. A comprehensive review of records was performed, with documentation of baseline characteristics, cardiac imaging, medications, and clinical course. Seventy-nine patients who had left ventricular ejection fraction (LVEF) declines temporally associated with cancer therapy were included. The most common malignancies were breast (46%) and hematologic (35%); 71% of the patients were female, and overall mean age was 52 years. The primary cancer therapeutics associated with LVEF decline included anthracyclines, trastuzumab, and tyrosine kinase inhibitors. The mean LVEF was 60% before cancer therapy and 40% after cancer therapy. The most common cardiac interventions included beta-blockers (84%) and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (83%). Mean LVEF after cardiac intervention rose to 53%; 77% of patients had LVEF recovery to ≥50%, and 68% of these patients had recovery within 6 months of starting cardiac therapy; 76% of patients were able to continue their planned cancer therapy.. With appropriate cardiac intervention, the majority of patients with LVEF decline from cancer therapy can achieve LVEF recovery and complete their cancer therapy.

Topics: Adult; Aged; Antineoplastic Agents; Cardiovascular Agents; Cohort Studies; Early Medical Intervention; Female; Humans; Male; Middle Aged; Neoplasms; Prognosis; Retrospective Studies; Ventricular Dysfunction, Left

Topics: Antineoplastic Agents; Cardiovascular Agents; Early Medical Intervention; Female; Humans; Male; Neoplasms; Ventricular Dysfunction, Left

Mineralocorticoid receptor(MR) antagonism reduces sudden cardiac death in heart failure, but the underlying mechanism remains poorly understood. Concurrent treatment with an MR antagonist during rapid ventricular pacing (RVP) prevents development of adverse ventricular electrophysiological remodeling, interstitial fibrosis, inflammatory cytokine gene activation, and ventricular tachyarrhythmia inducibility without diminishing the extent of systolic dysfunction. We hypothesized that attenuating preexistent inflammatory pathways and myocardial fibrosis with eplerenone after systolic heart failure is established by rapid pacing can reduce electrical activation delays and arrhythmia vulnerability.. Dogs subjected to RVP for 8 weeks in the absence or presence of eplerenone treatment during the final 4 weeks of pacing were assessed by echocardiography, electrophysiology study,ventricular fibrosis measurements, and inflammatory cytokine mRNA expression analysis. Eplerenone reversed preexistent ventricular activation delays, interstitial fibrosis, inflammatory cytokine (interleukin-6, tumor necrosis factor-α) gene overexpression, and arrhythmia vulnerability in ventricular paced dogs with heart failure. Eplerenone failed to improve left ventricular systolic dysfunction or chamber enlargement. A correlation between severity of fibrosis and ventricular arrhythmia inducibility was found.. MR antagonism regresses rapid pacing-induced electrical delays, inflammatory cytokine gene activation, and fibrosis in heart failure. Ventricular arrhythmia vulnerability in heart failure is correlated with extent of fibrosis and electrical activation delays during premature excitation.

Topics: Action Potentials; Animals; Anti-Inflammatory Agents; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Cardiovascular Agents; Disease Models, Animal; Dogs; Eplerenone; Fibrosis; Heart Failure; Hypertrophy, Left Ventricular; Inflammation Mediators; Interleukin-6; Male; Mineralocorticoid Receptor Antagonists; Myocardium; Spironolactone; Time Factors; Tumor Necrosis Factor-alpha; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling

To explore changes in healthcare professionals' views about the diagnosis and management of heart failure since a study in 2003.. Focus groups and a national online cross-sectional survey.. Focus groups (n=8 with a total of 56 participants) were conducted in the North East of England using a phenomenological framework and purposive sampling, informing a UK online survey (n=514).. 4 categories were identified as contributing to variations in the diagnosis and management of heart failure. Three previously known categories included: uncertainty about clinical practice, the value of clinical guidelines and tensions between individual and organisational practice. A new category concerned uncertainty about end-of-life care. Survey responses found that confidence varied among professional groups in diagnosing left ventricular systolic dysfunction (LVSD): 95% of cardiologists, 93% of general physicians, 66% of general practitioners (GPs) and 32% of heart failure nurses. For heart failure with preserved ejection fraction (HFpEF), confidence levels were much lower: 58% of cardiologists, 43% of general physicians, 7% of GPs and 6% of heart failure nurses. Only 5-35% of respondents used natriuretic peptides for LVSD or HFpEF. Confidence in interpreting test findings was fundamental to the use of all diagnostic tests. Clinical guidelines were reported to be helpful when diagnosing LVSD by 33% of nurses and 50-56% of other groups, but fell to 5-28% for HFpEF. Some GPs did not routinely initiate diuretics (23%), ACE-inhibitors (22%) or β-blockers (38%) for LVSD for reasons including historical teaching, perceived side effects and burden of monitoring. For end-of-life care, there was no consensus about responsibility for heart failure management.. Reported differences in the way heart failure is diagnosed and managed have changed little in the past decade. Variable access to diagnostic tests, modes of care delivery and non-uniform management approaches persist. The current National Health Service (NHS) context may not be conducive to addressing these issues.

Topics: Adult; Attitude of Health Personnel; Cardiovascular Agents; Cross-Sectional Studies; Disease Management; England; Female; Focus Groups; General Practice; Health Care Surveys; Health Services Accessibility; Heart Failure; Humans; Male; Middle Aged; Practice Patterns, Physicians'; Professional Competence; Qualitative Research; Surveys and Questionnaires; Terminal Care; Ventricular Dysfunction, Left; Young Adult

Topics: Antineoplastic Agents; Cardiovascular Agents; Early Medical Intervention; Female; Humans; Male; Neoplasms; Ventricular Dysfunction, Left

Topics: Antineoplastic Agents; Cardiovascular Agents; Early Medical Intervention; Female; Humans; Male; Neoplasms; Ventricular Dysfunction, Left

Topics: Adolescent; Benzazepines; Cardiomyopathy, Dilated; Cardiovascular Agents; Humans; Ivabradine; Male; Treatment Outcome; Ventricular Dysfunction, Left

The aim of the study was to assess heart rate reduction for a acute decompensated heart failure in patients with reduced left ventricular systolic function and in patients with heart failure without significant reduction in ejection fraction. Were examined 79 patients with an ejection fraction less than 40%. 38 of them took If-channel blocker, ivabradine, 41 amounted to a control group. A group of patients with diastolic dysfunction was 48 patients (23 in the treatment of ivabradine and 25 subgroups of control). During the 14 days of observation it was found that the positive effect of reducing the sinus rate by ivabradine was observed in patients with diastolic dysfunction. In this group of patients on the background of decreasing heart rate, improves the passive diastolic properties of the left ventricle and an increase in the distance traveled by the patients during 6-minute walk test compared with the control group. The data obtained in our study support the use of ivabradine in patients with acute decompensated heart failure. The most significant changes in hemodynamic parameters and functional status were obtained in patients with diastolic dysfunction. Given the small sample, the results need to be further confirmed in larger clinical trials.

Topics: Acute Disease; Aged; Benzazepines; Cardiovascular Agents; Dose-Response Relationship, Drug; Drug Monitoring; Echocardiography; Exercise Test; Female; Heart Failure, Systolic; Heart Rate; Humans; Ivabradine; Male; Middle Aged; Statistics as Topic; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

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

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

Contemporary therapeutic options have led to substantial improvement in survival of patients with heart failure. However, limited evidence is available specifically on idiopathic dilated cardiomyopathy. We thus examined changes in prognosis of a large idiopathic dilated cardiomyopathy cohort systematically followed during the past 30 years.. From 1977 to 2011, 603 consecutive patients (age, 53±12 years; 73% men; left ventricular ejection fraction, 32±10%) fulfilling World Health Organization criteria for idiopathic dilated cardiomyopathy, including negative coronary angiography, were followed up for 8.8±6.3 years. Patients were subdivided in 4 enrollment periods on the basis of heart failure treatment eras: (1) 1977-1984 (n=66); (2) 1985-1990 (n=102); (3) 1991-2000 (n=197); (4) 2001-2011 (n=238). Rates of patients receiving angiotensin-converting enzyme inhibitors/angiotensin receptors blockers, β-blockers, and devices at final evaluation increased from 56%, 12%, 8% (period 1) to 97%, 86%, 17% (period 4), respectively (P<0.05). There was a trend toward enrollment of older patients with less severe left ventricular dilatation and dysfunction during the years. During follow-up, 271 patients (45%) reached a combined end point including death (heart failure related, n=142; sudden death, n=71; and noncardiac, n=22) or cardiac transplant (n=36). A more recent enrollment period represented the most powerful independent predictor of favorable outcome {period 2 versus 1 (hazard ratio [HR], 0.64; P=0.04), period 3 versus 1 (HR, 0.35; P<0.001), period 4 versus 1 (HR, 0.14; P<001)}. Each period was associated with a 42% risk reduction versus the previous one (HR, 0.58; 95% confidence interval, 0.50-0.67; P<0.001), reflecting marked decreases in heart failure-related mortality and sudden death (period 4 versus 1: HR, 0.10; P<001 and HR, 0.13; P<0.0001, respectively).. Evidence-based treatment has led to dramatic improvement in the prognosis of idiopathic dilated cardiomyopathy during the past 3 decades. The benefits of controlled randomized trials can be replicated in the real world, emphasizing the importance of tailored follow-up and long-term continuity of care.

Topics: Adolescent; Adrenergic beta-Antagonists; Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiac Resynchronization Therapy; Cardiomyopathy, Dilated; Cardiovascular Agents; Chi-Square Distribution; Death, Sudden, Cardiac; Disease Progression; Evidence-Based Medicine; Female; Heart Failure; Heart Transplantation; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Outcome and Process Assessment, Health Care; Proportional Hazards Models; Risk Factors; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling; Young Adult

Takotsubo cardiomyopathy (TC) is increasingly recognised in patients presenting with features of acute coronary syndrome. We present a single centre experience of TC with medium term follow up.. Fifty-two consecutive patients presenting with a diagnosis of TC were included. The clinical presentation, complications, baseline and follow-up echocardiograms and cardiac magnetic resonance imaging were analysed.. Fifty-one patients were female. A stressful event preceded presentation in 37 (71%) patients. Chest pain was the most common symptom (83%). Two patients presented with an out-of-hospital cardiac arrest. ST segment elevation (40%) and global T wave inversion (44%) were the most frequent electrocardiogram changes. Left ventricular assessment demonstrated typical apical ballooning in 41 patients and 11 patients demonstrated the mid-wall variant. In-hospital complications occurred in 11 patients (21%) and included acute pulmonary oedema (n = 2), cardiogenic shock (n = 5); two of whom had a significant left ventricular outflow gradient, atrial fibrillation (n = 1), left ventricular thrombus (n = 2) and a cerebrovascular event (n = 2). Left ventricular function at presentation and follow up was compared in 40 patients. The mean ejection fraction in this group at presentation was 47% (20-70%) compared with that at follow up of 63% (44-76%). There were no significant complications or recurrences at follow up.. While TC is a reversible condition with low rates of complications and recurrence at follow up it is, as demonstrated in our cohort, associated with significant in-hospital morbidity in a proportion of patients.

Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Cardiac Catheterization; Cardiovascular Agents; Chest Pain; Diagnosis, Differential; Electrocardiography; Female; Follow-Up Studies; Heart Arrest; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Platelet Aggregation Inhibitors; Pulmonary Edema; Queensland; Shock, Cardiogenic; Stress, Psychological; Stroke Volume; Takotsubo Cardiomyopathy; Ultrasonography; Ventricular Dysfunction, Left

Diabetes mellitus has been associated with changes in the structure and function of the myocardium manifesting in the early stages of the disease as subtle systolic and diastolic dysfunction; the role of dobutamine stress echocardiography (DSE) in this setting remains unclear. We sought to evaluate the prevalence of dobutamine-induced systolic dysfunction amongst diabetic patients with normal at rest left ventricular ejection fraction and no coronary artery disease and to investigate whether an optimized therapeutic approach can reverse these abnormalities. 1,363 patients with DM referred to our echocardiography laboratory for DSE between January 2008 and June 2010 were prospectively investigated. Patients with normal left ventricular ejection fraction (LVEF) at rest and significant deterioration during peak dobutamine infusion (defined as a ≥10% decrease) in the absence of coronary artery disease or vasospasm were enrolled. They received on top of their usual treatment 5 mg perindopril and had their glycemic control intensified. At 60 days, all of them were controlled for clinical status and underwent a control DSE. 18 patients were included, there were 9 males and 9 females, mean age was 66.1 ± 10.2 years. All the patients had type II DM with a mean duration of 12.7 ± 6.6 years. They all had normal at rest echocardiographic findings with no wall motion abnormalities; mean LVEF was 62 ± 6%. At peak dobutamine, LVEF significantly deteriorated in all the patients with a mean 15 ± 5% decrease compared to baseline. After therapeutic optimization, Glycated haemoglobin improved from 8.53 ± 2.05% to 6.8 ± 0.6% (δ HbA1C = 1.73%, P = 0.001), mean LVEF at peak dobutamine infusion evolved from 47.17 ± 4.2% pre-optimization to 58 ± 4.8% at control (10.83% improvement; P < 0.001). In patients with DM and normal at rest LVEF, Dobutamine infusion during DSE can induce a significant deterioration in LVEF in the absence of coronary artery disease or vasospasm. This specific condition could be largely reversed through an optimized therapy based on a tighter metabolic control and a more stringent renin-angiotensin-aldosterone system inhibition.

Topics: Adrenergic Agonists; Adult; Aged; Aged, 80 and over; Biomarkers; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Dobutamine; Echocardiography, Stress; Female; France; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Male; Middle Aged; Predictive Value of Tests; Prevalence; Prospective Studies; Stroke Volume; Systole; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Amides; Animals; Cardiovascular Agents; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Female; Fumarates; Humans; Male; Myocardial Infarction; Renin; Ventricular Dysfunction, Left; Ventricular Remodeling

Rheumatic heart disease (RHD) remains an important health issue for indigenous women of child-bearing age in northern Australia. However, the influence of RHD on maternal outcomes with current clinical practice is unclear.. To determine maternal cardiac complications and obstetric outcomes in patients with RHD.. Retrospective case note analysis of women with RHD who received obstetric care between July 1999 and May 2010 at Cairns Base Hospital in north Queensland. Outcome measures were obstetric interventions and outcomes, cardiac interventions and complications, stratified according to a cardiac risk score (CRS).. Ninety-five confinements occurred in 54 patients, of whom 52 were Indigenous Australians. There were no maternal or neonatal deaths. With a CRS of 0, cardiac complications occurred in 0 of 70 confinements; with a CRS of 1, complications occurred in 5 of 17 confinements (29%); with a CRS of >1, complications occurred in 2 of 4 confinements (50%). Another four patients were first diagnosed with RHD after developing acute pulmonary oedema during the peripartum period..   RHD has a major impact on maternal cardiac outcomes. However, with current management practices, maternal and fetal mortality are low, and the incidence of complications is predictable based on known risk factors.

Topics: Adult; Cardiovascular Agents; Delivery, Obstetric; Female; Heart Valve Diseases; Humans; Infant, Newborn; Native Hawaiian or Other Pacific Islander; Parity; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Puerperal Disorders; Pulmonary Edema; Queensland; Retrospective Studies; Rheumatic Heart Disease; Ultrasonography; Ventricular Dysfunction, Left; Young Adult

Coarctation of the aorta (CoA) is a common congenital anomaly that is usually treated in infancy or childhood. Adult patients with coarctation have a high incidence of associated cardiac disorders, including valve diseases, atrial fibrillation and ischemic heart disease. Most patients with uncorrected CoA die before reaching the age of 50 from complications such as myocardial infarction, intracranial hemorrhage, congestive heart failure (HF), infective endocarditis or aortic dissection. We report the case of a 65 year-old woman admitted to hospital with symptoms of heart failure NYHA class IV. She had been treated for several years for refractory arterial hypertension and concomitant stenocardia (II CCS). The symptoms of HF had been increasing over several months. Outpatient echocardiography examination revealed significant, increasing mitral and tricuspid valve regurgitation with progressive left ventricular dysfunction. The patient was referred for surgical repair of the mitral and tricuspid valves. In-hospital echocardiography and angiography revealed descending aorta discontinuity at the level of the aortic isthmus. This congenital disease revealed during hospitalization was determined to be the underlying cause of all the symptoms the patient presented. Due to the clinical status of the patient, she was discharged from surgical procedures and put on medication.

Topics: Aged; Aortic Coarctation; Aortography; Cardiac Catheterization; Cardiovascular Agents; Delayed Diagnosis; Echocardiography, Doppler; Female; Heart Failure; Humans; Mitral Valve Insufficiency; Predictive Value of Tests; Tricuspid Valve Insufficiency; Ventricular Dysfunction, Left

Left ventricle ejection fraction (LVEF) ≤ 30-35% is widely accepted as a cut-off for primary prevention with an implantable cardiac defibrillator (ICD) in patients with both ischaemic and non-ischaemic cardiomyopathy supposedly on optimal medical therapy. This study reports evolutions of LVEF and treatments of patients implanted in our institution with an ICD for primary prevention of sudden death, after 2 years of follow-up.. Among 84 patients with LVEF under 35% implanted between 2005 and 2007, 28 (33%) had improved their LVEF >35% after the 2 years of follow-up. During this period, even if Beta-blockers (98%) and renin-angiotensin system (RAS) blockers (95%) were already initially prescribed, treatments were significantly optimized with improvement of maximal doses of beta-blockers and RAS blockers at 2 year follow-up compared with initial prescription (62 vs. 37% and 68 vs. 45%, respectively). In patients with improved LVEF, a trend toward a better treatment optimization and revascularization procedures (in the sub-group of ischaemic patients) were observed compared with non-improved LVEF patients.. In our study of patients with prophylactic ICD, one-third of them have improved their LVEF after a 2 year follow-up. Despite an optimal medical therapy at the time of implantation, we were able to further improve the maximal treatment doses after implantation. This study highlights the issue of what should be considered as 'optimal' therapy and the possibility of improvement of LVEF related to a real optimized treatment before implantation.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathies; Cardiovascular Agents; Chi-Square Distribution; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Female; France; Humans; Male; Middle Aged; Primary Prevention; Recovery of Function; Retrospective Studies; Risk Factors; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Doxorubicin, an anthracycline antibiotic commonly used as a chemotherapeutic agent for breast cancer, is well known to cause cardiotoxicity. We report the case of an active, otherwise healthy 57-year-old breast cancer survivor who, 17 years after chemotherapy, presented with symptoms of overt heart failure. She had no cardiac risk factors, and neither laboratory nor imaging findings suggested myocarditis or dilated cardiomyopathy. Echocardiographic findings and differential diagnosis led us to attribute her condition to late doxorubicin-induced cardiomyopathy. By virtue of tapered medical therapy, her left ventricular ejection fraction improved from 0.20 to 0.55 in 8 months, and she was asymptomatic after 1 year. The reversibility of left ventricular dysfunction in our patient and the very late appearance of cardiotoxicity secondary to doxorubicin therapy raise questions about the pathogenesis and prevalence of late doxorubicin-induced cardiomyopathy and how to improve outcomes in patients who present with related symptoms of heart failure.

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Cardiomyopathies; Cardiovascular Agents; Chemotherapy, Adjuvant; Doxorubicin; Electrocardiography; Female; Heart Failure; Humans; Magnetic Resonance Imaging; Mastectomy, Segmental; Middle Aged; Recovery of Function; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Cardiac fibrosis is a hallmark of heart disease and plays a vital role in cardiac remodeling during heart diseases, including hypertensive heart disease. Hexarelin is one of a series of synthetic growth hormone secretagogues (GHSs) possessing a variety of cardiovascular effects via action on GHS receptors (GHS-Rs). However, the role of hexarelin in cardiac fibrosis in vivo has not yet been investigated. In the present study, spontaneously hypertensive rats (SHRs) were treated with hexarelin alone or in combination with a GHS-R antagonist for 5 wk from an age of 16 wk. Hexarelin treatment significantly reduced cardiac fibrosis in SHRs by decreasing interstitial and perivascular myocardial collagen deposition and myocardial hydroxyproline content and reducing mRNA and protein expression of collagen I and III in SHR hearts. Hexarelin treatment also increased matrix metalloproteinase (MMP)-2 and MMP-9 activities and decreased myocardial mRNA expression of tissue inhibitor of metalloproteinase (TIMP)-1 in SHRs. In addition, hexarelin treatment significantly attenuated left ventricular (LV) hypertrophy, LV diastolic dysfunction, and high blood pressure in SHRs. The effect of hexarelin on cardiac fibrosis, blood pressure, and cardiac function was mediated by its receptor, GHS-R, since a selective GHS-R antagonist abolished these effects and expression of GHS-Rs was upregulated by hexarelin treatment. In summary, our data demonstrate that hexarelin reduces cardiac fibrosis in SHRs, perhaps by decreasing collagen synthesis and accelerating collagen degradation via regulation of MMPs/TIMP. Hexarelin-reduced systolic blood pressure may also contribute to this reduced cardiac fibrosis in SHRs. The present findings provided novel insights and underscore the therapeutic potential of hexarelin as an antifibrotic agent for the treatment of cardiac fibrosis.

Topics: Animals; Blood Pressure; Cardiovascular Agents; Collagen Type I; Collagen Type III; Disease Models, Animal; Fibrosis; Gene Expression Regulation; Heart Diseases; Hydroxyproline; Hypertension; Hypertrophy, Left Ventricular; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Myocardium; Oligopeptides; Rats; Rats, Inbred SHR; Rats, Wistar; Receptors, Ghrelin; RNA, Messenger; Time Factors; Tissue Inhibitor of Metalloproteinase-1; Ventricular Dysfunction, Left; Ventricular Function, Left

Cardiomyopathy refers to nonspecific myocardial dysfunction that may be due to a variety of causes. Viral illnesses have long been known to cause cardiomyopathy, and the list of viral causes is extensive. Influenza infection is a rare cause of myocarditis. Recent reports, however, indicate that influenza A (H1N1) can cause acute myocarditis and cardiomyopathy in adults and fulminant myocarditis in children as seen during the 2009 global outbreak of the H1N1 influenza virus. The following presents a case series of adult patients with acute reversible cardiomyopathy associated with influenza A (H1N1) infection (see Table 1 for patient characteristics).

Topics: Acute Disease; Aged; Antiviral Agents; Cardiomyopathies; Cardiovascular Agents; Female; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Male; Middle Aged; Myocarditis; Recovery of Function; Treatment Outcome; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Function, Left

Vasopeptidase inhibition (VPI), a therapeutic strategy by dual inhibition of both ACE and neutral endopeptidase 24.11, has not shown a prognostic benefit over ACE inhibition in chronic severe heart failure (CHF). Nevertheless, the effects of early treatment by VPI on cardiac remodelling have not been well assessed. We analysed the effects of early chronic VPI (50 mg/kg/day Omapatrilat) on cardiac remodelling and neurohumoral function during the progression of rapid ventricular pacing-induced heart failure in rabbits (early left ventricular dysfunction [ELVD]: 10 days at 330 bpm, CHF: further 10 days at 360 bpm). VPI-treated animals (ELVD-VPI n = 6; CHF-VPI n = 8) and placebo treated animals (ELVD n = 6; CHF n = 7) were compared with control rabbits (CTRL n = 5). LV fractional shortening (FS) and enddiastolic diameter (LVEDD) were assessed by echocardiography (12 MHz probe). LV BNP- and LV IL-6 gene expression was analysed quantitatively by real time PCR. Neurohumoral function was assessed by ANP, cGMP, plasma renin activity (PRA) and Aldosterone. In ELVD, LVEDD and atrial mass were significantly increased (both p < 0.05). This increase was markedly attenuated by VPI (both p < 0.05 vs. placebo). CHF was associated with a further increase in atrial mass and an increase in LV mass (both p < 0.05), which was again attenuated by VPI (atrial mass, p < 0.05 vs. untreated). LV BNP mRNA was significantly increased in CHF (p < 0.05 vs. control), and chronic VPI completely abolished this increase in ELVD and significantly attenuated it in CHF (p < 0.05 vs. CHF-placebo). Beyond that, the increase of cGMP was augmented by chronic VPI (p < 0.05 vs. placebo in CHF) in heart failure and that of Aldosterone was attenuated (p < 0.05 vs. placebo in ELVD), whereas PRA was temporarily increased (p < 0.05 vs. placebo in ELVD). Combined inhibition of ACE and NEP by VPI significantly inhibits early cardiac remodelling and LV BNP gene expression. If initiated early enough, it may slow down cardiac remodelling and represents a promising therapeutic strategy in progressive heart failure.

Topics: Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiomegaly; Cardiovascular Agents; Disease Models, Animal; Gene Expression Regulation; Heart Failure; Male; Natriuretic Peptide, Brain; Neprilysin; Pyridines; Rabbits; Renin; Renin-Angiotensin System; RNA, Messenger; Tachycardia; Thiazepines; Ventricular Dysfunction, Left; Ventricular Remodeling

Detection of cardiac recovery that allows long-term cardiac stability after ventricular assist device (VAD) explantation is a major goal. After normalization of ventricular diameters during unloading, the pre-explant left ventricular ejection fraction (LVEF) allows the detection of patients with the potential to remain stable after VAD explantation. However, some patients with LVEF >45 before VAD explantation show early recurrence of heart failure (HF). We aimed to find out if unstable improvement can be recognized before VAD explantation.. Among 96 patients weaned from VADs since 1995, a relatively homogenous group of 53 patients with nonischemic chronic cardiomyopathy (CCM) was selected for the study. The pre-explant stability of major parameters of LV function, size, and geometry that were measured by echocardiography during serial "off-pump" trials was tested for relationship with cardiac stability after VAD explantation. LVEF, systolic peak wall motion velocity (Sm), end-diastolic diameter (LVEDD), end-diastolic relative wall thickness (RWT(ED)) and end-diastolic short/long-axis ratio (S/L(ED)) were selected for evaluation. In postweaning unstable patients, the selected parameters showed relevant instability already before VAD explantation during the time period between best cardiac improvement and VAD explantation and also during the final off-pump trial just before VAD explantation. For all parameters, there were significant differences (P<0.05) in pre-explant changes between patients with and without postweaning cardiac stability. Using the optimal cutoff values obtained from receiver-operating characteristic analysis, we found for our selected parameters predictive values for postexplant cardiac stability of ≥1 year, ≥3 years, and ≥5 years, ranging between 94 and 100, 92, and 100, and 78 and 100, respectively. Using for all parameter changes the cutoff value of 10, we found similar predictive values for cardiac stability of ≥1 year, ≥3 years, and ≥5 years, ranging between 93 and 97, 90 and 96, and 83 and 92, respectively.. Our results strongly suggest the possibility to improve the prediction of postexplant transplant/VAD-free outcome in CCM patients with cardiac improvement during VAD support by analyzing the pre-explant stability of several LV off-pump echocardiographic parameters during serial off-pump trials.

Topics: Adolescent; Adult; Aged; Cardiovascular Agents; Combined Modality Therapy; Device Removal; Female; Heart Failure; Heart-Assist Devices; Humans; Hypertrophy, Left Ventricular; Kaplan-Meier Estimate; Male; Middle Aged; Organ Size; Prognosis; Proportional Hazards Models; Recovery of Function; Recurrence; Retrospective Studies; Stroke Volume; Treatment Outcome; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Function, Left; Young Adult

A 34-year-old female with a diarrhoeal illness and palpitations was found to have an abnormal ECG and troponin T. Subsequent coronary angiography identified angiographically normal epicardial coronary arteries with moderate impairment of left ventricular systolic function due to mid-ventricular akinesis with apical hyperkinesis. Cardiac MRI, performed 1 week later, demonstrated complete resolution of ventricular dysfunction and a diagnosis of atypical variant stress cardiomyopathy, due to gastrointestinal illness, was proposed.

Topics: Adult; Anxiety; Cardiovascular Agents; Coronary Angiography; Diarrhea; Female; Humans; Remission, Spontaneous; Takotsubo Cardiomyopathy; Troponin T; Ventricular Dysfunction, Left

The authors present a case of a 70-year-old woman in whom clinical picture of an acute coronary syndrome with ST segment elevation was suggestive of takotsubo cardiomyopathy (TC). Chest pain, extensive ECG changes and typical TC left ventricular contraction pattern were preceded by emotional and physical stress, while in coronary angiography no atherosclerotic lesions were found. There was however left anterior descending coronary artery myocardial bridging with total systolic compression. Following treatment with beta-blocker and diltiazem, spectacular left ventricle function improvement, with near total recovery after 6 months was observed. Magnetic resonance imaging detected the presence of subendocardial late gadolinium enhancement indicative of postmyocardial scar.

Topics: Adrenergic beta-Antagonists; Aged; Cardiovascular Agents; Diagnosis, Differential; Diltiazem; Drug Therapy, Combination; Female; Humans; Magnetic Resonance Imaging; Myocardial Bridging; Myocardial Infarction; Takotsubo Cardiomyopathy; Ventricular Dysfunction, Left

We have previously shown that a specific combination of drug therapy and left ventricular assist device unloading results in significant myocardial recovery, sufficient to allow pump removal, in two thirds of patients with dilated cardiomyopathy receiving a Heartmate I pulsatile device. However, this protocol has not been used with nonpulsatile devices.. We report the results of a prospective study of 20 patients who received a combination of angiotensin-converting enzymes, β-blockers, angiotensin II inhibitors, and aldosterone antagonists followed by the β₂-agonist clenbuterol and were regularly tested (echocardiograms, exercise tests, catheterizations) with the pump at low speed. Before left ventricular assist device insertion, patient age was 35.2 ± 12.6 years (16 male patients), patients were on 2.0 ± 0.9 inotropes, 7 (35) had an intra-aortic balloon pump, 2 were hemofiltered, 2 were ventilated, 3 had a prior Levitronix device, and 1 had extracorporeal membrane oxygenation. Cardiac index was 1.39 ± 0.43 L · min⁻¹ · m⁻², pulmonary capillary wedge pressure was 31.5 ± 5.7 mm Hg, and heart failure history was 3.4 ± 3.5 years. One patient was lost to follow-up and died after 240 days of support. Of the remaining 19 patients, 12 (63.2) were explanted after 286 ± 97 days. Eight had symptomatic heart failure for ≤6 months and 4 for >6 months (48 to 132 months). Before explantation, at low flow for 15 minutes, ejection fraction was 70 ± 7, left ventricular end-diastolic diameter was 48.6 ± 5.7 mm, left ventricular end-systolic diameter was 32.3 ± 5.7 mm, mV(O₂) was 21.6 ± 4 mL · kg⁻¹ · min⁻¹, pulmonary capillary wedge pressure was 5.9 ± 4.6 mm Hg, and cardiac index was 3.6 ± 0.6 L · min⁻¹ · m⁻². Estimated survival without heart failure recurrence was 83.3 at 1 and 3 years. After a 430.7 ± 337.1-day follow-up, surviving explants had an ejection fraction of 58.1 ± 13.8, left ventricular end-diastolic diameter of 59.0 ± 9.3 mm, left ventricular end-systolic diameter of 42.0 ± 10.7 mm, and mV(O₂) of 22.6 ± 5.3 mL · kg⁻¹ · min⁻¹.. Reversal of end-stage heart failure secondary to nonischemic cardiomyopathy can be achieved in a substantial proportion of patients with nonpulsatile flow through the use of a combination of mechanical and pharmacological therapy.

Topics: Adult; Cardiomyopathy, Dilated; Cardiovascular Agents; Clenbuterol; Female; Heart Failure; Heart-Assist Devices; Humans; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left; Young Adult

To assess heart failure therapies in diabetic patients with preserved as compared to impaired systolic ventricular function.. 3304 patients with heart failure from 9 different studies were included (mean age 63 ± 14 years); out of these, 711 subjects had preserved left ventricular ejection fraction (≥ 50%) and 994 patients in the whole cohort suffered from diabetes.. The majority (>90%) of heart failure patients with reduced ejection fraction (SHF) and diabetes were treated with an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) or with beta-blockers. By contrast, patients with diabetes and preserved ejection fraction (HFNEF) were less likely to receive these substance classes (p < 0.001) and had a worse blood pressure control (p < 0.001). In comparison to patients without diabetes, the probability to receive these therapies was increased in diabetic HFNEF patients (p < 0.001), but not in diabetic SHF patients. Aldosterone receptor blockers were given more often to diabetic patients with reduced ejection fraction (p < 0.001), and the presence and severity of diabetes decreased the probability to receive this substance class, irrespective of renal function.. Diabetic patients with HFNEF received less heart failure medication and showed a poorer control of blood pressure as compared to diabetic patients with SHF. SHF patients with diabetes were less likely to receive aldosterone receptor blocker therapy, irrespective of renal function.

Topics: Aged; Blood Pressure; Cardiovascular Agents; Comorbidity; Cross-Sectional Studies; Diabetes Complications; Female; Germany; Glomerular Filtration Rate; Guideline Adherence; Heart Failure; Humans; Kidney; Logistic Models; Male; Middle Aged; Practice Guidelines as Topic; Stroke Volume; Systole; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

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

Two hundred patients at steady-state on long-term perhexiline were identified retrospectively. The ratio of maintenance dose to steady-state plasma concentration (dose:[Px]) was correlated with the following putative determinants via simple and multiple linear regression analyses: age, weight, left ventricular ejection fraction (LVEF), and creatinine clearance (CrCl, Cockroft-Gault formula). A Mann-Whitney U test was performed to determine if severe left ventricular systolic impairment affected maintenance dose.. Advanced age, left ventricular systolic impairment, and renal impairment were frequently encountered. Using simple linear regression, age was a negative correlate of dose:[P] (R = 0.23, P = 0.001), whereas weight (R = 0.27, P = 0.0001) and CrCl (R = 0.30, P < 0.0001) were positive correlates. Mann-Whitney U analysis showed no difference between dose: [Px] among patients with LVEF of less than 30% versus 30% or greater. Advancing age was strongly associated with decreasing weight (R = -0.45, P < 0.00001) and calculated CrCl varied directly with weight, as expected (R = 0.66, P < 0.0001). Stepwise multiple linear regression using age, LVEF, CrCl, and weight as potential predictors of dose:[P] yielded only weight as a significant determinant.. Perhexiline has become a "last-line" agent for refractory angina as a result of complex pharmacokinetics and potential toxicity. Use has increased predictably in the aged and infirm who have exhausted standard medical and surgical therapeutic options. Beyond genotype, the effect of patient characteristics on maintenance dose has not been explored in detail. In this study, dose requirement declined with age in a frail and wasting population as a result of weight-related pharmacokinetic factors. LVEF had no apparent effect on maintenance dose and should not be considered a contraindication to use.. A weight-adjusted starting dose may facilitate the safe and effective prescription of perhexiline and is calculated by 50 + 2 × weight (kg) mg/d, rounded to the closest 50 mg/day.

Topics: Aged; Aged, 80 and over; Aging; Angina Pectoris; Body Weight; Cardiovascular Agents; Creatinine; Humans; Middle Aged; Perhexiline; Renal Insufficiency; Retrospective Studies; Ventricular Dysfunction, Left

Topics: Capillary Leak Syndrome; Cardiovascular Agents; Combined Modality Therapy; Diagnosis, Differential; Emergencies; Fatal Outcome; Female; Fluid Therapy; Humans; Hypotension, Orthostatic; Middle Aged; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Pasteurella Infections; Pasteurella multocida; POEMS Syndrome; Respiration, Artificial; Shock, Septic; Skin Diseases, Bacterial; Ventricular Dysfunction, Left

Ejection fraction (EF) is crucial information when studying the use and effectiveness of therapies in patients with heart failure (HF) and myocardial infarction (MI). We aimed to assess the validity of claims data-based definitions of systolic dysfunction (SD).. We identified 1072 patients with EF recorded for an HF/MI hospitalization in Medicare linked with pharmacy data and national HF/MI registries in 1999-2006. Thirteen claims-based definitions for SD were developed using a single or combination of ICD-9 diagnosis codes and cardiovascular medications use. We calculated sensitivity, specificity, and positive predictive values (PPVs) using recorded EFs as the gold standard.. Using an EF cutoff of 45%, the definitions based on digoxin use and no atrial fibrillation or flutter had the highest PPVs (76% to 84%) and specificity (>97%) but low sensitivity (6%-14%). As we varied the EF cutoff between 50% and 25%, the specificity decreased by 3%, but the PPVs decreased by 52%. We observed potential differences in the PPVs by patients' characteristics. In a hypothetical study assessing implantable defibrillator effectiveness, using our definition to identify patients with SD would underestimate the effectiveness by 3% to 24%. In another hypothetical study comparing two classes of angiotensin system blockers where SD was considered confounding, our definition introduced ~43% misclassification bias.. Claims-based definitions for SD had excellent specificity and good PPV but low sensitivity. The definitions with good PPV could be used for cohort identification or confounding adjustment by restriction and would result in relatively small misclassification bias albeit limited generalizability.

Topics: Aged; Aged, 80 and over; Bias; Cardiovascular Agents; Confounding Factors, Epidemiologic; Databases, Factual; Female; Heart Failure; Hospitalization; Humans; Insurance Claim Review; International Classification of Diseases; Male; Medicare; Myocardial Infarction; Predictive Value of Tests; Sensitivity and Specificity; Stroke Volume; United States; Ventricular Dysfunction, Left

Congenital heart defects that have a component of right ventricular outflow tract obstruction, such as tetralogy of Fallot, are frequently palliated in childhood by disruption of the pulmonary valve. Although this can provide an initial improvement in quality of life, these patients are often left with severe pulmonary valve insufficiency. Over time, this insufficiency can lead to enlargement of the right ventricle and to the deterioration of right ventricular systolic and diastolic function. Pulmonary valve replacement in these patients decreases right ventricular volume overload and improves right ventricular performance. To date, few studies have examined the effects of pulmonary valve replacement on left ventricular function in patients with biventricular dysfunction. We sought to perform such an evaluation.Records of adult patients who had undergone pulmonary valve replacement from January 2003 through November 2006 were analyzed retrospectively. We reviewed preoperative and postoperative echocardiograms and calculated left ventricular function in 38 patients.In the entire cohort, the mean left ventricular ejection fraction increased by a mean of 0.07 after pulmonary valve replacement, which was a statistically significant change (P < 0.01). In patients with preoperative ejection fractions of less than 0.50, mean ejection fractions increased by 0.10.We conclude that pulmonary valve replacement in patients with biventricular dysfunction arising from severe pulmonary insufficiency and right ventricular enlargement can improve left ventricular function. Prospective studies are needed to verify this finding.

Topics: Adult; Cardiac Surgical Procedures; Cardiovascular Agents; Child; Child, Preschool; Female; Heart Defects, Congenital; Heart Valve Prosthesis Implantation; Humans; Hypertrophy, Right Ventricular; Male; Middle Aged; Pulmonary Valve; Pulmonary Valve Insufficiency; Recovery of Function; Reoperation; Retrospective Studies; Stroke Volume; Texas; Treatment Outcome; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right; Ventricular Function, Left; Ventricular Function, Right; Young Adult

The STICH trial showed that CABG surgery does not necessarily improve cardiovascular outcomes in patients with coronary artery disease and left ventricular dysfunction who are receiving optimal medical therapy. However, surgical revascularization should still be considered if the coronary artery disease is severe and viable myocardium can be identified.

Topics: Cardiovascular Agents; Coronary Artery Bypass; Coronary Artery Disease; Evidence-Based Medicine; Humans; Patient Selection; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Treatment Outcome; Ventricular Dysfunction, Left

Patients with heart failure may experience psychiatric disorders for which electroconvulsive therapy (ECT) is indicated. Little is known, however, about the safety of ECT in these patients. We assessed the safety of ECT in patients with a history of heart failure and decreased left ventricular systolic heart function.. We conducted a retrospective review of the medical records of 35 patients with a history of heart failure and reduced left ventricular systolic heart function who underwent ECT at Mayo Clinic in Rochester, Minnesota, between January 1995 and December 2009.. Of the 35 patients, 18 (51%) were women. The median age was 77 years (range, 54-92 years). The median left ventricular ejection fraction was 30% (range, 15%-40%). The 35 patients underwent 513 ECT sessions (median number of sessions per patient, 10; range, 1-44). The 35 patients tolerated ECT well. No patient died or experienced decompensated heart failure, myocardial ischemia, or myocardial infarction during or within 24 hours after an ECT session. Prophylactic intravenous β-blockers were given to patients who, during previous ECT sessions, had marked hypertension (eg, systolic blood pressure >180-200 mm Hg) or a heart rate greater than 100 beats per minute; overall, this prophylaxis was used in 26 patients during 413 ECT sessions (80% of the total number of ECT sessions). Three patients experienced temporary, non-life-threatening cardiac arrhythmias.. Electroconvulsive therapy was safe in 35 patients with a history of heart failure and decreased left ventricular systolic heart function treated at our institution.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Anesthesia; Anesthetics; Blood Pressure; Cardiovascular Agents; Electroconvulsive Therapy; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Oxygen Inhalation Therapy; Retrospective Studies; Ventricular Dysfunction, Left

Guidelines have been established for the treatment of patients with heart failure (HF) and left ventricular dysfunction, but renal dysfunction might limit adherence to these guidelines. Few data have characterized the use of guideline-recommended therapy for patients with HF, left ventricular dysfunction, and renal dysfunction who are treated in outpatient settings. The Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF) was a prospective study of patients receiving treatment as outpatients in cardiology practices in the United States. The rates of adherence to 7 guideline-recommended therapies were evaluated for patients with a left ventricular ejection fraction of < or = 35%. The estimated glomerular filtration rate was estimated using the Modification of Diet in Renal Disease formula for 13,164 patients who were categorized as having stage 1 through stage 4/5 chronic kidney disease (CKD). More than 1/2 (52.2%) of the patients had stage 3 or 4/5 CKD. Older patients and women were at increased risk of higher stage CKD, and the rates of co-morbid health conditions were significantly greater among patients with more severe CKD. The patients with more severe CKD were significantly less likely to receive all interventions except cardiac resynchronization therapy. However, multivariate analysis controlling for patient characteristics revealed that the severity of CKD was an independent predictor of adherence to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy but not to any of the 6 other guideline-recommended measures. In conclusion, these results confirm that CKD is common in patients with HF and left ventricular dysfunction but is not independently associated with adherence to guideline-recommended therapy in outpatient cardiology practices, with the exception of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy.

Topics: Aged; Cardiovascular Agents; Creatinine; Echocardiography; Female; Follow-Up Studies; Glomerular Filtration Rate; Guideline Adherence; Heart Failure; Humans; Kidney Failure, Chronic; Magnetic Resonance Imaging; Male; Middle Aged; Outpatients; Practice Guidelines as Topic; Prognosis; Prospective Studies; Renal Insufficiency; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

Topics: Benzazepines; Cardiovascular Agents; Coronary Artery Disease; Endpoint Determination; Heart Rate; Humans; Ivabradine; Randomized Controlled Trials as Topic; Ventricular Dysfunction, Left

Methylphenidate is a potent central nervous system stimulant that exerts its effects by increasing synaptic levels of dopamine and norepinephrine. It has become key to treating attention deficit-hyperactivity disorder (ADHD) in children and adolescents. As the use of stimulant medications has ballooned in the past decade, so too has awareness of the cardiovascular complications of these drugs. Effects on heart rate and blood pressure as well as tachyarrhythmias have been well described. However, acute cardiomyopathy and pericarditis secondary to methylphenidate use has been rarely reported. We report the case of a 17-year-old male who developed chest pain, elevated cardiac biomarkers, and acute left ventricular dysfunction following a single dose of methylphenidate. The risk of cardiomyopathy in the setting of methylphenidate treatment should prompt further study on the safety of this drug, and lead to ways of identifying those at risk of developing these complications.

Topics: Acute Disease; Adolescent; Angina Pectoris; Attention Deficit Disorder with Hyperactivity; Cardiomyopathies; Cardiovascular Agents; Central Nervous System Stimulants; Drug Therapy, Combination; Electrocardiography; Humans; Male; Methylphenidate; Pericarditis; Ventricular Dysfunction, Left

We investigated treatment of 200 consecutive patients hospitalized for heart failure (HF). Of the 200 patients, 100 (50%) had an abnormal left ventricular ejection fraction (LVEF) and 100 (50%) had a normal LVEF. Although in-hospital mortality was significantly increased in patients with HF and an abnormal LVEF, the duration of hospitalization and the NYHA class at discharge were similar in patients with HF and abnormal or normal LVEF.

Topics: Aged; Cardiovascular Agents; Female; Heart Failure; Hospitalization; Humans; Male; Patient Compliance; Sodium, Dietary; Ventricular Dysfunction, Left

The aim of this study was to report a series of patients with stress cardiomyopathy precipitated by the intravenous administration of catecholamines and beta-receptor agonists.. Stress cardiomyopathy is a syndrome of transient cardiac dysfunction precipitated by intense emotional or physical stress. Excessive sympathetic stimulation is believed to be central to the pathogenesis of this disorder, but a causal link has not been convincingly demonstrated.. We observed 9 cases of stress cardiomyopathy precipitated immediately by the intravenous administration of epinephrine (n = 6) or dobutamine (n = 3). Patients were evaluated with coronary angiography and with serial echocardiography, electrocardiography, and cardiac enzymes.. The median age was 44 years (interquartile range [IQR]: 30 to 48 years), and 7 (78%) were woman. Troponin-I was mildly elevated (median 4.07 ng/ml, IQR: 0.47 to 5.63 ng/ml), but none of the patients undergoing angiography had obstructive coronary disease. All patients developed corrected QT interval (QTc interval) prolongation (median QTc interval 504 ms, IQR: 477 to 568 ms) within 24 h of receiving drug. All 3 previously described variants of left ventricular "ballooning" (apical, midventricular, and basal) were observed. The median ejection fraction on admission was 35% (IQR: 35% to 40%). During follow-up (median 7 days, IQR: 4 to 13 days) there was recovery of left ventricular systolic function in all patients (median ejection fraction 55%, IQR: 40% to 60%, p < 0.001 vs. admission).. Exposure to catecholamines and beta-receptor agonists used routinely during procedures and diagnostic tests can precipitate all the features of stress cardiomyopathy, including cardiac isoenzyme elevation, QTc interval prolongation, and rapidly reversible cardiac dysfunction. These observations strongly implicate excessive sympathetic stimulation as central to the pathogenesis of this unique syndrome.

Topics: Adrenergic beta-Agonists; Adult; Cardiomyopathies; Cardiovascular Agents; Catecholamines; Dobutamine; Epinephrine; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Ventricular Dysfunction, Left

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

Few data are available in the literature regarding the characteristics and prognosis of asymptomatic patients with idiopathic dilated cardiomyopathy (DCM).. To determine the frequency with which patients affected by DCM are diagnosed in the asymptomatic state as well as to evaluate the natural history of such patients and the factors influencing their outcome. Moreover, we sought to compare the outcome of asymptomatic patients with that of patients with signs of overt heart failure at the time of first evaluation.. We analyzed the data of 747 patients with DCM enlisted in the Heart Muscle Disease Registry of Trieste from 1978 to 2007. We divided our population into four groups; group 1 comprised 118 asymptomatic [New York Heart Association (NYHA) I] patients without a history of congestive symptoms (16%), group 2 comprised 102 asymptomatic (NYHA I) patients (14%) with a positive anamnesis for heart failure stabilized in medical therapy, group 3 comprised 327 patients (44%) with signs of mild heart failure (NYHA II) and group 4 comprised 200 patients (26%) in NYHA III-IV. During the follow-up of 112+/-63 months, 46 (21%) of 220 asymptomatic patients with DCM died or underwent heart transplantation. By Cox proportional model, left ventricular ejection fraction of 30% or less was a unique independent predictor either for death/heart transplantation (hazard ratio 3.15, 95% confidence interval 1.5-6.7, P=0.003) or for sudden death/major ventricular arrhythmias (hazard ratio 3.9, 95% confidence interval 1.7-9.3, P=0.002). Patients from group 1 had a trend for a better outcome with respect to those from group 2 (P=0.06). In comparison with the asymptomatic patients, those with signs of overt heart failure at baseline had a worse prognosis.. The proportion of asymptomatic patients with DCM at the moment of first evaluation at our center is significant (30%). Among them, those without a previous history of heart failure had a less advanced disease and a trend for a better long-term outcome on optimal medical treatment. Therefore, early diagnosis may offer better long-term quality of life and even better survival. Further studies on larger populations are indicated.

Topics: Adult; Cardiomyopathy, Dilated; Cardiovascular Agents; Disease Progression; Female; Heart Failure; Heart Transplantation; Humans; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Proportional Hazards Models; Registries; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome; Ultrasonography; Ventricular Dysfunction, Left; Young Adult

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

Hydroxyl radicals and hydrogen peroxide are involved in the pathogenesis of systolic dysfunction in diabetic rats, but the precise mechanisms and the effect of antioxidant therapy in diabetic subjects have not been elucidated. We aimed to evaluate the effects of dimethylthiourea (DMTU), a potent hydroxyl radical scavenger, on both force-dependent and velocity-dependent indexes of cardiac contractility in streptozotocin (STZ)-induced early and chronic diabetic rats. Seventy-two hours and 8 wk after STZ (55 mg/kg) injection, diabetic rats were randomized to either DMTU (50 mg x kg(-1) x day(-1) ip) or vehicle treatment for 6 and 12 wk, respectively. All rats were then subjected to invasive hemodynamic studies. Maximal systolic elastance (E(max)) and maximum theoretical flow (Q(max)) were assessed by curve-fitting techniques in terms of the elastance-resistance model. Both normalized E(max) (E(maxn)) and afterload-adjusted Q(max) (Q(maxad)) were depressed in diabetic rats, concomitant with altered myosin heavy chain (MHC) isoform composition and its upstream regulators, such as myocyte enhancer factor-2 (MEF-2) and heart autonomic nervous system and neural crest derivatives (HAND). In chronic diabetic rats, DMTU markedly attenuated the impairment in Q(maxad) and normalized the expression of MEF-2 and eHAND and MHC isoform composition but exerted an insignificant benefit on E(maxn). Regarding preventive treatment, DMTU significantly ameliorated both E(maxn) and Q(maxad) in early diabetic rats. In conclusion, our study shows that DMTU has disparate effects on Q(maxad) and E(maxn) in chronic diabetic rats. The advantage of DMTU in chronic diabetic rats might involve normalization of MEF-2 and eHAND, as well as reversal of MHC isoform switch.

Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Cardiovascular Agents; Diabetes Mellitus, Experimental; Elasticity; Free Radical Scavengers; Hemodynamics; Hydroxyl Radical; Male; Myocardial Contraction; Myocardium; Myogenic Regulatory Factors; Myosin Heavy Chains; Oxidative Stress; Protein Isoforms; Rats; Rats, Wistar; Thiourea; Time Factors; Ventricular Dysfunction, Left

We present an unusual case of cardiomyopathy in a two month old male infant with a grade-I systolic murmur. Echocardiographic examination disclosed left ventricular (LV), dysplasia with saw-tooth like inwards myocardial projections extending from the lateral walls towards the LV cavity. There was mild LV systolic dysfunction with apical hypokinesia. Cardiovascular magnetic resonance demonstrated in detail these cross bridging muscular projections originating from the inferior interventricular septum and lateral LV wall, along with areas of hypokinesis at the LV septum and apex in a noncoronary distribution, without any late gadolinium enhancement. We have termed this condition saw-tooth cardiomyopathy because of the very characteristic appearance.

Topics: Cardiomyopathies; Cardiovascular Agents; Heart Failure; Heart Murmurs; Humans; Infant; Magnetic Resonance Imaging; Male; Myocardium; Ventricular Dysfunction, Left; Ventricular Septum

Cardiomyopathy is a generic term for any heart disease in which the heart muscle is involved and functions abnormally. Recent developments and ongoing research in cardiology have led to descriptions of 3 previously less recognized or incompletely characterized cardiomyopathies. These entities are being increasingly noticed in adult patient populations. Primary care providers and cardiovascular specialists need to be aware of the clinical features of these illnesses and the best strategies for diagnosis and management. We have discussed the causes and diagnostic methods for these newly described cardiomyopathies and ways to manage them.

Topics: Adolescent; Adult; Aged; Arrhythmogenic Right Ventricular Dysplasia; Cardiovascular Agents; Female; Humans; Middle Aged; Takotsubo Cardiomyopathy; Ventricular Dysfunction, Left

Spontaneous coronary artery dissection (SCAD) is a potentially life-threatening entity with a variety of clinical presentations. We report a patient who presented with chest pain and angiographic evidence of coronary dissection. Due to the rapid resolution of symptoms and benign-appearing nature of the dissection, no intervention was pursued and the patient was maintained on medical therapy. She represented 2 days later with substernal chest pain, dynamic EKG changes, positive cardiac biomarkers and a transient depression of her left ventricular function.

Topics: Aortic Dissection; Cardiovascular Agents; Coronary Aneurysm; Female; Humans; Middle Aged; Recurrence; Systole; Ventricular Dysfunction, Left

This report describes the prompt resolution of an apical left ventricular (LV)-thrombus complicating transient apical ballooning in a 74-year-old woman. The patient was admitted to our emergency department with acute chest pain and ST-elevation on the electrocardiogram. Coronary angiography showed normal coronary arteries and LV-angiography demonstrated the presence of apical ballooning akinesis associated with basal hypercontraction. Echocardiography and MRI studies confirmed the presence of LV-apex akinesis and detected an apical thrombus. Follow-up echocardiography on day 12 before discharge of the patient, revealed a marked improvement of regional contractility of the LV-apex and surprisingly the complete resolution of the LV-apical thrombus. The patient was diagnosed with takotsubo cardiomyopathy.

Topics: Aged; Angina Pectoris; Anticoagulants; Cardiomyopathies; Cardiovascular Agents; Female; Heart Diseases; Humans; Remission Induction; Thrombosis; Ventricular Dysfunction, Left

Chronic heart failure is an increasingly frequent clinical syndrome, characterized by reduced physical performance, dyspnea and an adverse prognosis. It is associated with age, indicating that it will become more common. Diagnosis requires the characterization of cardiac dysfunction and a precise definition of the underlying cardiac disease. Treatment guidelines of the cardiac societies, which were updated 2005, recommend therapy with ACE-inhibitors, AT1 receptor antagonists, beta-blockers, aldosterone antagonists and digitalis. It is essential, however, to consider the individual circumstances such as underlying disease, age as well as the frequent complications and comorbidities.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Chronic Disease; Digitalis Glycosides; Dose-Response Relationship, Drug; Drug Administration Schedule; Heart Failure; Hemodynamics; Humans; Mineralocorticoid Receptor Antagonists; Practice Guidelines as Topic; Ventricular Dysfunction, Left

Takotsubo cardiomyopathy is an acute cardiac syndrome characterized by transient LV regional wall motion abnormalities (with peculiar apical ballooning appearance), chest pain or dyspnea, ST-segment elevation and minor elevations of cardiac enzyme levels. A 68-year-old woman was admitted to the Emergency Department because of sudden onset chest pain occurred while transferring her daughter, who had earlier suffered a major seizure, to the hospital. The EKG showed sinus tachycardia with ST-segment elevation in leads V2-V3 and ST-segment depression in leads V5-V6, she was, thus, referred for emergency coronary angiography. A pre-procedural transthoracic echocardiogram revealed regional systolic dysfunction of the LV walls with hypokinesis of the mid-apical segments and hyperkinesis of the basal segments. Coronary angiography showed patent epicardial coronary arteries; LV angiography demonstrated the characteristic morphology of apical ballooning with hyperkinesis of the basal segments and hypokinesis of the mid-apical segments. The post-procedural course was uneventful; on day 5 after admission the echocardiogram revealed full recovery of apical and mid-ventricular regional wall-motion abnormalities.. Takotsubo cardiomyopathy is a relatively rare, unique entity that has only recently been widely appreciated. Acute stress has been indicated as a common trigger for the transient LV apical ballooning syndrome, especially in postmenopausal women. The present report is a typical example of stress-induced takotsubo cardiomyopathy in a Caucasian Italian postmenopausal woman.

Topics: Aged; Cardiomyopathies; Cardiovascular Agents; Coronary Angiography; Echocardiography; Electrocardiography; Female; Humans; Ventricular Dysfunction, Left

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

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

Recent advances in pharmacological and pacemaker-based treatments for heart failure (HF) have brought about significant improvements in left ventricular function.. To identify the proportion of treated systolic HF patients in whom left ventricular systolic function improves and/or returns to normal.. This was a retrospective analysis of 221 HF patients. Improvement in left ventricular function was defined as an improvement in ejection fraction (LVEF) of > or =10% on echocardiography. Return to normal was defined as an improvement of LVEF to > or =50% and a reduction in left ventricular end diastolic diameter to < or =55 mm. Changes in BNP were also recorded.. Improvement in LVEF was observed in 44.3% of patients and return to normal systolic function in 10.9%, only 2.3% had both a return to normal echocardiographic parameters and a BNP<100 pg/ml. A higher percentage of the improved group were on target doses of beta-blockers (p=0.004). Baseline BNP was not a predictor of improvement. There was a trend towards a reduction in HF readmissions in the improved group (p=0.07) but no difference in the risk of death or all-cause readmission.. While a substantial proportion of treated HF patients have an improvement in left ventricular function over time, only a small proportion return to normal dimensions and LVEF, underlining the permanent nature of ventricular damage in the vast majority of patients.

Topics: Aged; Cardiac Pacing, Artificial; Cardiovascular Agents; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Male; Myocardial Contraction; Natriuretic Peptide, Brain; Recovery of Function; Retrospective Studies; Stroke Volume; Systole; Treatment Outcome; Ventricular Dysfunction, Left

Stress cardiomyopathy is a reversible left ventricular dysfunction precipitated by emotional stress. Affected patients are generally women, whose symptoms are similar to myocardial infarction with reversible apical dyskinesis associated with hypercontractile basal segments and no evidence for hemodynamically significant coronary arterial stenoses by angiography. We report the case of an 82-year-old woman who presented with acute onset of chest pain after emotional stress and with reversible left ventricular dysfunction consisting of akinesis of the midventricular segments and hyperkinesis of the basal and apical segments.

Topics: Aged, 80 and over; Angina Pectoris; Cardiovascular Agents; Coronary Angiography; Echocardiography, Four-Dimensional; Electrocardiography; Female; Humans; Myocardial Contraction; Takotsubo Cardiomyopathy; Treatment Outcome; Ventricular Dysfunction, Left

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

Heart failure (HF) affects approximately 5 million persons in the United States each year. HF is predominantly a disease of the elderly: Approximately 80% of patients hospitalized with HF are older than age 65. Approximately one-half of older adult patients with CHF have a decreased ejection fraction. Elderly patients with HF and a reduced LVEF have a higher mortality than elderly patients with HF with a normal LVEF. Despite numerous excellent studies showing the efficacy of appropriate drugs in reducing mortality in patients with HF and a reduced LVEF, these medications are underutilized in the treatment of HF. This article discusses the latest guidelines from the American College of Cardiology/American Heart Association for the treatment of patients with HF and a reduced LVEF.

Topics: Aged; Cardiac Output, Low; Cardiovascular Agents; Combined Modality Therapy; Death, Sudden, Cardiac; Exercise; Heart Failure; Humans; Risk Factors; Secondary Prevention; Treatment Outcome; Ventricular Dysfunction, Left

Heart failure has an annual mortality rate ranging from 5% to 75%. The purpose of the study was to develop and validate a multivariate risk model to predict 1-, 2-, and 3-year survival in heart failure patients with the use of easily obtainable characteristics relating to clinical status, therapy (pharmacological as well as devices), and laboratory parameters.. The Seattle Heart Failure Model was derived in a cohort of 1125 heart failure patients with the use of a multivariate Cox model. For medications and devices not available in the derivation database, hazard ratios were estimated from published literature. The model was prospectively validated in 5 additional cohorts totaling 9942 heart failure patients and 17,307 person-years of follow-up. The accuracy of the model was excellent, with predicted versus actual 1-year survival rates of 73.4% versus 74.3% in the derivation cohort and 90.5% versus 88.5%, 86.5% versus 86.5%, 83.8% versus 83.3%, 90.9% versus 91.0%, and 89.6% versus 86.7% in the 5 validation cohorts. For the lowest score, the 2-year survival was 92.8% compared with 88.7%, 77.8%, 58.1%, 29.5%, and 10.8% for scores of 0, 1, 2, 3, and 4, respectively. The overall receiver operating characteristic area under the curve was 0.729 (95% CI, 0.714 to 0.744). The model also allowed estimation of the benefit of adding medications or devices to an individual patient's therapeutic regimen.. The Seattle Heart Failure Model provides an accurate estimate of 1-, 2-, and 3-year survival with the use of easily obtained clinical, pharmacological, device, and laboratory characteristics.

Topics: Adult; Aged; Aged, 80 and over; Area Under Curve; Cardiac Pacing, Artificial; Cardiovascular Agents; Cohort Studies; Combined Modality Therapy; Comorbidity; Defibrillators, Implantable; Diuretics; Female; Follow-Up Studies; Forecasting; Heart Failure; Heart-Assist Devices; Hemoglobins; Humans; Life Expectancy; Lymphocyte Count; Male; Middle Aged; Models, Cardiovascular; Multivariate Analysis; Proportional Hazards Models; Prospective Studies; Randomized Controlled Trials as Topic; ROC Curve; Survival Analysis; Survival Rate; Treatment Outcome; Ventricular Dysfunction, Left

The management of asymptomatic severe mitral regurgitation remains controversial. The aim of this study was to evaluate the outcome of a watchful waiting strategy in which patients are referred to surgery when symptoms occur or when asymptomatic patients develop left ventricular (LV) enlargement, LV dysfunction, pulmonary hypertension, or recurrent atrial fibrillation.. A total of 132 consecutive asymptomatic patients (age 55+/-15 years, 49 female) with severe degenerative mitral regurgitation (flail leaflet or valve prolapse) were prospectively followed up for 62+/-26 months. Patients underwent serial clinical and echocardiographic examinations and were referred for surgery when the criteria mentioned above were fulfilled. Overall survival was not statistically different from expected survival either in the total group or in the subgroup of patients with flail leaflet. Eight deaths were observed. Thirty-eight patients developed criteria for surgery (symptoms, 24; LV criteria, 9; pulmonary hypertension or atrial fibrillation, 5). Survival free of any indication for surgery was 92+/-2% at 2 years, 78+/-4% at 4 years, 65+/-5% at 6 years, and 55+/-6% at 8 years. Patients with flail leaflet tended to develop criteria for surgery slightly but not significantly earlier. There was no operative mortality. Postoperative outcome was good with regard to survival, symptomatic status, and postoperative LV function.. Asymptomatic patients with severe degenerative mitral regurgitation can be safely followed up until either symptoms occur or currently recommended cutoff values for LV size, LV function, or pulmonary hypertension are reached. This management strategy is associated with good perioperative and postoperative outcome but requires careful follow-up.

Topics: Aged; Atrial Fibrillation; Cardiovascular Agents; Case Management; Comorbidity; Disease Progression; Disease-Free Survival; Female; Follow-Up Studies; Humans; Hypertension, Pulmonary; Hypertrophy, Left Ventricular; Life Tables; Male; Middle Aged; Mitral Valve Insufficiency; Mitral Valve Prolapse; Prospective Studies; Survival Analysis; Time Factors; Treatment Outcome; Ultrasonography; Ventricular Dysfunction, Left

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

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Defibrillators; Defibrillators, Implantable; Heart Failure; Humans; Mineralocorticoid Receptor Antagonists; Practice Guidelines as Topic; Sodium Chloride Symporter Inhibitors; Ventricular Dysfunction, Left; Ventricular Fibrillation

Raised resting heart rate (HR) is associated with increased cardiovascular and total mortality. Ivabradine is a new specific HR-reducing agent, which has been shown to have antianginal and anti-ischemic properties in patients with stable angina. Because patients with coronary artery disease and left ventricular dysfunction are at high risk of cardiac events and death, we hypothesized that they could derive particular benefit from a specific HR-lowering agent such as ivabradine.. BEAUTIFUL is a multicenter, randomized, international, double-blind placebo-controlled trial to evaluate the superiority of ivabradine over placebo in reducing cardiovascular events in patients with stable coronary artery disease and left ventricular systolic dysfunction (ejection fraction < or = 39%). The primary end point is the composite of cardiovascular mortality and hospital admission for acute myocardial infarction or new onset or worsening of heart failure. This event-driven study will randomize 9650 patients and continue until 950 primary end points have occurred, providing 90% power to detect a 19% reduction in relative risk. In approximately 660 centers, men and women aged > or = 55 years if nondiabetic and > or = 18 years if diabetic are randomized to placebo or oral ivabradine (5 mg twice daily for 2 weeks then target dose of 7.5 mg twice daily). Follow-up is expected to last between 18 and 36 months.. The first patient was randomized in January 2005.. BEAUTIFUL will be the first major outcome trial of a specific HR-reducing agent. The study results are expected in 2008.

Topics: Adult; Benzazepines; Cardiovascular Agents; Coronary Artery Disease; Double-Blind Method; Female; Heart Rate; Hospitalization; Humans; Ivabradine; Male; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Randomized Controlled Trials as Topic; Research Design; Ventricular Dysfunction, Left

The objective was to assess the cardiac effects of growth hormone (GH) therapy. Anthracycline-treated childhood cancer survivors frequently have reduced left ventricular (LV) wall thickness and contractility, and GH therapy may affect these factors.. We examined serial cardiac findings for 34 anthracycline-treated childhood cancer survivors with several years of GH therapy and baseline cardiac z scores similar to those of a comparison group (86 similar cancer survivors without GH therapy).. LV contractility was decreased among GH-treated patients before, during, and after GH therapy (-1.08 SD below the age-adjusted population mean before therapy and -1.88 SD 4 years after therapy ceased, with each value depressed below normal). Contractility was higher in the control group than in the GH-treated group, with this difference being nearly significant. The GH-treated children had thinner LV walls before GH therapy (-1.38 SD). Wall thickness increased during GH therapy (from -1.38 SD to -1.09 SD after 3 years of GH therapy), but the effect was lost shortly after GH therapy ended and thickness diminished over time (-1.50 SD at 1 year after therapy and -1.96 SD at 4 years). During GH therapy, the wall thickness for the GH-treated group was greater than that for the control group; however, by 4 years after therapy, there was no difference between the GH-treated group and the control group.. GH therapy among anthracycline-treated survivors of childhood cancer increased LV wall thickness, but the effect was lost after therapy was discontinued. The therapy did not affect the progressive LV dysfunction.

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Body Height; Cardiovascular Agents; Child; Child, Preschool; Enalapril; Female; Heart Ventricles; Hemodynamics; Human Growth Hormone; Humans; Hypertrophy, Left Ventricular; Hypopituitarism; Infant; Male; Myocardial Contraction; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Survivors; Ultrasonography; Ventricular Dysfunction, Left

Nesiritide is a recombinant brain-type natriuretic peptide (BNP), which decreases pulmonary arterial (PA) pressures and myocardial oxygen consumption while increasing coronary flow and urine output. Mitral valve (MV) surgery in patients with severe mitral regurgitation (MR), impaired left ventricular function, and pulmonary hypertension is associated with a high operative mortality. We hypothesized that the perioperative use of Nesiritide is safe, and may improve surgical outcomes.. From May 2003 to August 2004, 14 patients (11 male, 3 female; mean age, 64 years [23-87 years]; mean systolic PA, 63 mm Hg [48-94 mm Hg]; mean ejection fraction, 36% [10-50%]), undergoing MV surgery (10 repairs, 2 replacements, and 2 rereplacements) for severe MR, were treated for a median of 24 hours (13-55 hours) preoperatively with intravenous Nesiritide. Expected mortality by EuroSCORE was 26% (7.8-59%) (5 reoperations). Concomitant procedures included tricuspid valve repair (n = 7), coronary artery bypass grafting (n = 5), and left atrial maze procedure (n = 3). Eleven patients received Nesiritide postoperatively during a mean duration of 22 hours (2-80 hours).. Operative mortality was 0%. Prior to surgery after BNP treatment, mean systolic PA pressure dropped to 39 mm Hg (p = 0.0003), pulmonary capillary wedge pressure to 15 mm Hg (p = 0.001), central venous pressure to 6 mm Hg (p = 0.002), and weight by 3.7 kg (p = 0.006). Postoperative median ventilation time was 14 hours (4-48 hours). All other major hemodynamic parameters (systemic blood pressure, heart rate, and cardiac output) remained constant. The treatment was well-tolerated in all patients.. Perioperative use of Nesiritide is safe, and may contribute to improved early outcomes in high-risk patients undergoing MV surgery. This may be due to improved ventricular loading conditions (decreased PA pressures, more effective diuresis) and/or a direct myocardial effect of BNP. Further prospective evaluation of the role of BNP in cardiac surgery is warranted.

Topics: Adult; Aged; Aged, 80 and over; Cardiac Surgical Procedures; Cardiovascular Agents; Female; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; Mitral Valve; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Prospective Studies; Ventricular Dysfunction, Left

It was the aim of the Euro Heart Survey on Heart Failure to assess whether patients are being treated according to current guidelines.. In Germany, patients were screened in 7 medical centers if their discharge diagnoses were myocardial infarction, a new episode of atrial fibrillation, or diabetes mellitus. Patients were enrolled if at least one additional criterion was fulfilled: (1) clinical diagnosis of heart failure, (2) hospital admission due to heart failure within the last 3 years, (3) therapy with loop diuretic, (4) medication for heart failure or ventricular dysfunction documented by echocardiography within the past 24 hours prior to death.. 2166 patients were screened of whom 747 were included in the study (478 men, 269 women). 93% of the patients suffered from heart failure. Despite the high number of patients with known heart failure (ischemic heart failure in 71%), only 72% received ACE inhibitors and 62% beta-blockers. Average daily dose met recommendations in only 63% of patients on ACE inhibitors and 54% on beta-blockers. 74% of the patients received diuretics (furosemide 36%, thiazide 34%, spironolactone 17%).. An inadequately low number of patients with heart failure receives medical therapy according to guidelines, despite all the overwhelming evidence for improved morbidity and mortality. Awareness of physicians needs to be improved.

Topics: Adrenergic beta-Antagonists; Age Factors; Aged; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Cardiovascular Agents; Diuretics; Drug Therapy, Combination; Europe; Female; Fibrinolytic Agents; Guideline Adherence; Health Surveys; Heart Failure; Humans; Male; Middle Aged; Patient Readmission; Practice Guidelines as Topic; Sex Factors; Sodium Potassium Chloride Symporter Inhibitors; Statistics as Topic; Survival Analysis; Ventricular Dysfunction, Left

Topics: Cardiac Surgical Procedures; Cardiovascular Agents; Chronic Disease; Combined Modality Therapy; Contraindications; Evidence-Based Medicine; Exercise; Germany; Health Behavior; Heart Failure; Humans; Life Style; Meta-Analysis as Topic; Prognosis; Randomized Controlled Trials as Topic; Treatment Outcome; Ventricular Dysfunction, Left

Rapid hemodynamic deterioration is caused by induction of brain death, but the exact mechanism is still uncertain. The aim of this study was to investigate the contribution of endothelin-1 by using endothelin-1 receptor antagonist (TAK-044) in a canine brain-death model.. Dogs were divided into 2 groups: (1) the TAK group, in which TAK-044 was intravenously injected 30 minutes before brain-death induction at a dose of 3 mg/kg; and (2) the control group. Brain death was induced by rapid inflation of a sub-durally placed balloon catheter. Left ventricular function and coronary flow reserve was compared between the 2 groups.. Brain death caused a transient hyperdynamic response followed by hemodynamic deterioration after 60 minutes in both groups. Left ventricular function, evaluated by the slope of the end-systolic pressure-volume relation was significantly decreased from 7.7 +/- 0.6 to 3.7 +/- 0.3 mm Hg/ml (p < 0.01) in the control group, but was not decreased in the TAK group (7.7 +/- 0.8 to 7.3 +/- 0.9 mm Hg/ml, p = 0.75). Coronary flow reserve, measured by direct injection of acetylcholine (3 microg) into the coronary artery, was significantly reduced at 60 minutes after brain death in the control group (264.8% to 176.6%, p < 0.01), but not in the TAK group (291.2% to 301.3%, p = 0.84). Exactly the same results were obtained when sodium nitroprusside (SNP; 100 microg) was administered.. TAK-044 can prevent the deterioration of left ventricular function and coronary flow reserve that follows induction of brain death, suggesting that endothelin-1 could play an important role in hemodynamic deterioration by impairment of coronary microcirculation after brain death.

Topics: Animals; Brain Death; Cardiovascular Agents; Coronary Circulation; Dogs; Endothelin Receptor Antagonists; Endothelin-1; Epinephrine; Hemodynamics; Norepinephrine; Peptides, Cyclic; Ventricular Dysfunction, Left; Ventricular Function, Left

Congestive heart failure (CHF) results in decreased cardiac sympathetic innervation.. The purpose of this study was to test the hypothesis that therapy with the vasopeptidase inhibitor omapatrilat (OMA) attenuates cardiac neuronal remodeling in CHF.. We induced CHF in dogs with rapid ventricular pacing for 5 weeks with (CHF+OMA group, n = 8) or without (CHF group, n = 10) concomitant OMA treatment (10 mg/kg twice daily). Cardiac catheterization and echocardiography were performed to determine cardiac structure and hemodynamic parameters. Myocardial nerve density was determined by immunocytochemical staining with anti-growth associated protein 43 (GAP43) and anti-tyrosine hydroxylase (TH) antibodies. Seven normal dogs were used as histologic controls.. In the CHF group, ascites developed in 3 dogs and 4 dogs died, compared with no ascites or death in the CHF+OMA group (P = .07). In the 6 CHF dogs that survived, all had atrial fibrosis, severely depressed left ventricular systolic function, and increased atrial and ventricular chamber size. OMA treatment decreased the atrial and ventricular chamber sizes and the degree of atrial fibrosis. Most CHF dogs showed severe myocardial denervation, although some showed normal or abnormally high nerve counts. OMA treatment prevented heterogeneous reduction of nerve density. The left ventricular TH-positive nerve densities were 128 +/- 170 microm(2)/mm(2), 261 +/- 185 microm(2)/mm(2), and 503 +/- 328 microm(2)/mm(2) (P < .05), and the atrial GAP43-positive nerve densities were 1,683 +/- 1,365 microm(2)/mm(2), 305 +/- 368 microm(2)/mm(2), and 1,278 +/- 1,479 microm(2)/mm(2) (P < .05) for the control, CHF, and CHF+OMA groups, respectively.. CHF results in heterogeneous cardiac denervation. Long-term OMA treatment prevented the reduction of nerve density and promoted beneficial cardiac structural remodeling.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Cardiovascular Agents; Disease Models, Animal; Dogs; Heart Atria; Heart Failure; Heart Ventricles; Hypertrophy, Left Ventricular; Male; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue; Pyridines; Renin; Stroke Volume; Thiazepines; Ventricular Dysfunction, Left; Ventricular Pressure; Ventricular Remodeling

The cardioprotective effects of (2S,3R,4S)-N'-benzyl- N"-cyano-N-(3,4-dihydro-2-dimethoxymethyl-3-hydro- xy-2-methyl-6-nitro-2H-benzopyran-4-yl)-guanidine (KR-31372) were evaluated against ischemic/reperfusion injury in isolated rat hearts in vitro and in anesthetized rats and dogs in vivo. In isolated perfused rat hearts subjected to a 30-min global ischemia/30-min reperfusion, KR-31372 (1-10 microM) significantly improved severe contracture (end-diastolic pressure and time to contracture), markedly reduced reperfusion lactate dehydrogenase release, and enhanced the recovery of reperfusion contractile function (left ventricular developed pressure and double product) in a concentration-dependent manner compared with the vehicle-treated group. In anesthetized rats subjected to a 45-min coronary occlusion and a 90-min reperfusion, intravenous KR-31372 dose-dependently reduced infarct size from 58.6% to 48.5, 48.1 and 39.6% at 0.3, 1.0 and 3.0 mg/kg, respectively (p < 0.05). In anesthetized beagle dogs that underwent a 1.5-hour occlusion followed by a 5-hour reperfusion, KR-31372 (2 mg/kg, i.v.) markedly reduced infarct size from 57.0% in controls to 28.0% (p < 0.05). The cardioprotective effects of KR-31372 on contractile function in globally ischemic rat hearts and on reperfusion injury in anesthetized rats were significantly reversed by pretreatment with selective adenosine triphosphate-sensitive potassium (K(ATP)) channel blockers, sodium 5-hydroxydecanoate and glibenclamide. Taken together, these results indicate that KR-31372 possesses potent cardioprotective effects in rats and dogs and its effects may be mediated by activation of mitochondrial K(ATP) channels.

Topics: Animals; Benzopyrans; Cardiovascular Agents; Coronary Circulation; Coronary Disease; Dogs; Dose-Response Relationship, Drug; Glyburide; Guanidines; Heart Rate; Hypoglycemic Agents; In Vitro Techniques; L-Lactate Dehydrogenase; Male; Myocardial Reperfusion Injury; Rats; Rats, Sprague-Dawley; Ventricular Dysfunction, Left

Left ventricular assist device (LVAD) treatment is known to lead to structural and functional cellular modifications in the heart. The relevance of these changes for clinical recovery is unknown.. We compared properties of cardiomyocytes obtained from tissue taken at explantation of the LVAD in patients with clinical recovery with those obtained from hearts of patients who did not show clinical recovery, thus requiring transplantation. Compared with myocytes taken at implantation, both the recovery and nonrecovery groups showed approximately 50% reduction in cell capacitance, an index of cell size. However, action potential duration shortened, L-type Ca2+ current fast inactivation was more rapid, and sarcoplasmic reticulum Ca2+ content was increased in the recovery compared with the nonrecovery group.. These results show that specific changes in excitation-contraction coupling, and not regression of cellular hypertrophy, are specifically associated with clinical recovery after LVAD and further identify sarcoplasmic reticulum Ca2+ handling as a key functional determinant in patients with heart failure.

Topics: Caffeine; Calcium; Calcium Channels, L-Type; Calcium Signaling; Cardiovascular Agents; Cell Size; Combined Modality Therapy; Heart Failure; Heart Transplantation; Heart Ventricles; Heart-Assist Devices; Humans; Ion Transport; Myocytes, Cardiac; Remission Induction; Sarcoplasmic Reticulum; Ventricular Dysfunction, Left

There is little information on the clinical and functional course of patients with heart failure secondary to dilated cardiomyopathy due to hypertension. The objectives of our study were to assess the clinical and functional course of these patients, and to identify possible predictors of prognosis.. We evaluated a series of 49 patients with this condition diagnosed in our hospital from 1994 to 2003. Mean age was 63(11) years, and 40% were women. Left ventricular ejection fraction was 30.1(4.8)%. Follow-up was 45(23) months (median, 41 months).. Four-year survival was 0.84, the 4-year rate of hospitalization due to heart failure was 0.12, and likelihood of readmission-free survival was 0.80 at 4 years. Left ventricular ejection fraction increased from 30.1(4.8)% to 57.6(13.5)% (P< .001). An unfavorable clinical and functional outcome at 4 years (death, readmission for heart failure or persistence of dilated cardiomyopathy) was recorded in only in 40% of the patients. Multivariate analysis with the Cox model showed appropriate control of blood pressure to be the only independent predictor of a favorable clinical outcome (absence of death or readmission for heart failure) (hazard ratio = 4.58; 95% CI, 1.32-9.83; P=.032).. The course of patients with severe dilated cardiomyopathy due to hypertension was favorable in 60% of cases. Adequate control of blood pressure was the only independent predictor of a favorable clinical outcome.

Topics: Cardiomyopathy, Dilated; Cardiovascular Agents; Female; Heart Failure; Humans; Hypertension; Male; Middle Aged; Multivariate Analysis; Prognosis; Recovery of Function; Survival Analysis; Systole; Treatment Outcome; Ventricular Dysfunction, Left

Diabetes mellitus has been recognized as a strong predictor of heart failure (HF) in patients with acute myocardial infarction (AMI). However, considerable controversy exists regarding the pathogenetic mechanisms of HF after AMI in diabetic patients. We hypothesized that the increased incidence of HF in diabetic patients was associated with a greater propensity for left ventricular (LV) remodeling.. A series of 325 patients (42 diabetics) with AMI successfully treated with primary angioplasty underwent serial 2D echocardiography from admission to 1 and 6 months and 6-month angiography. No significant difference was found between diabetics and nondiabetics regarding baseline clinical, angiographic, and echocardiographic characteristics, as well as 6-month restenosis and reocclusion rates. At 6 months, a similar incidence of LV remodeling was observed in diabetics and nondiabetics (33% versus 25%; P=0.234), with similar patterns of changes in LV volumes and LV global and regional systolic function. At 5 years, the incidence of HF was higher in the diabetics (43% versus 20%, P=0.001). Diabetes was found to be an independent predictor of HF at 5 years (hazard ratio, 1.8; P=0.0366). However, LV remodeling was predictive of HF in the nondiabetics (P=0.023) but not in the diabetics (P=0.123). In a subgroup of patients, higher LV chamber stiffness (as assessed by echocardiography) was detected in the diabetics with HF.. The more frequent progression to HF in the diabetics after AMI is not explained by a greater propensity for LV remodeling. Other factors, such as diastolic dysfunction, may play a role.

Topics: Aged; Angioplasty, Balloon; Cardiac Catheterization; Cardiovascular Agents; Combined Modality Therapy; Coronary Restenosis; Diabetes Complications; Disease Progression; Echocardiography; Female; Follow-Up Studies; Heart Failure; Heart Ventricles; Humans; Incidence; Italy; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Recurrence; Systole; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Remodeling

In 2003, the Centers for Medicaid and Medicare Services recommended QRS duration as a means to identify MADIT II-like patients suitable for implanted cardiac defibrillator (ICD) therapy. We compared the ability of microvolt T-wave alternans and QRS duration to identify groups at high and low risk of dying among heart failure patients who met MADIT II criteria for ICD prophylaxis.. Patients with MADIT II characteristics and sinus rhythm had a microvolt T-wave alternans exercise test and a 12-lead ECG. Our primary end point was 2-year all-cause mortality. Of 177 MADIT II-like patients, 32% had a QRS duration >120 ms, and 68% had an abnormal (positive or indeterminate) microvolt T-wave alternans test. During an average follow-up of 20+/-6 months, 20 patients died. We compared patients with an abnormal microvolt T-wave alternans test to those with a normal (negative) test, and patients with a QRS >120 ms with those with a QRS < or =120 ms; the hazard ratios for 2-year mortality were 4.8 (P=0.020) and 1.5 (P=0.367), respectively. The actuarial mortality rate was substantially lower among patients with a normal microvolt T-wave alternans test (3.8%; 95% confidence interval: 0, 9.0) than the mortality rate in patients with a narrow QRS (12.0%; 95% confidence interval: 5.6, 18.5). The corresponding false-negative rates are 3.5% and 10.2%, respectively.. Among MADIT II-like patients, a microvolt T-wave alternans test is better than QRS duration at identifying a high-risk group and also better at identifying a low-risk group unlikely to benefit from ICD therapy.

Topics: Aged; Arrhythmias, Cardiac; Cardiovascular Agents; Case Management; Combined Modality Therapy; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Electrocardiography; False Negative Reactions; Female; Heart Failure; Humans; Life Tables; Male; Middle Aged; Myocardial Infarction; Prognosis; Prospective Studies; Risk; Survival Analysis; Treatment Outcome; United States; Ventricular Dysfunction, Left

This study was designed to examine the use of cardiovascular medications and outcomes in patients with heart failure (HF) and renal dysfunction.. Renal insufficiency is associated with poorer outcomes in patients with HF, but the mechanisms are uncertain. In particular, the degree of therapeutic nihilism in these patients, and whether it is appropriate, is unclear.. This was a prospective cohort study with a one-year follow-up.. In 6,427 patients with cardiologist-diagnosed HF and angiographically proven coronary artery disease (mean age 69 years; 65% men; one-year mortality, 10%), 39% had creatinine clearances <60 ml/min. Patients with renal insufficiency were less likely to be prescribed angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, statins, or aspirin (all p < 0.001). However, users of aspirin (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.57 to 0.85), statins (OR 0.79, 95% CI 0.64 to 0.97), and beta-blockers (OR 0.75, 95% CI 0.62 to 0.90) were less likely to die in the subsequent 12 months than nonusers, irrespective of renal function (all OR adjusted for covariates including atherosclerotic burden and ejection fraction). Although ACE inhibitor users with creatinine clearances > or =60 ml/min had lower 12-month mortality (OR 0.72, 95% CI 0.48 to 0.99), ACE inhibitor users with clearances <60 ml/min did not (OR 1.21, 95% CI 0.97 to 1.51).. Renal insufficiency is common in patients with HF and coronary artery disease, and these patients have more advanced coronary atherosclerosis. Patients with renal insufficiency are less likely to be prescribed efficacious therapies, but have better outcomes if they receive these medications.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Cardiovascular Agents; Cause of Death; Cohort Studies; Comorbidity; Coronary Artery Disease; Creatinine; Drug Utilization; Female; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Failure, Chronic; Likelihood Functions; Male; Medical Futility; Middle Aged; Odds Ratio; Survival Analysis; Ventricular Dysfunction, Left

We describe a patient who developed severe ventricular dysfunction and cardiogenic shock after intense emotional stress. Her subsequent course was favorable, with complete recovery of left ventricular systolic function. The coronary arteries were normal and no specific etiologic agent was demonstrated. Her clinical picture was compatible with transient left ventricular apical ballooning. [I123]metaiodobenzyl guanidine cardiac scintigraphy showed a marked decrease in cardiac sympathetic nerve activity. We discuss the pathophysiologic mechanisms of this syndrome.

Topics: Aged; Cardiovascular Agents; Echocardiography, Doppler; Electrocardiography; Female; Heart Ventricles; Humans; Shock, Cardiogenic; Stress, Psychological; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

We investigated the role of endothelin-A (ETA) and endothelin-B (ETB) receptors in ischemia/reperfusion-induced cardiac dysfunction and norepinephrine overflow using isolated rat hearts. According to the Langendorff technique, isolated hearts were subjected to 40 minutes of global ischemia followed by 30 minutes of reperfusion. Ischemia/reperfusion led to decreases in left ventricular developed pressure and coronary flow, and an increase in left ventricular end-diastolic pressure compared with pre-ischemic basal levels. An ETB receptor antagonist A-192621 at 1 microM worsened ischemia/reperfusion-induced cardiac dysfunction. In contrast, an ETA receptor antagonist ABT-627 at 5 microM with or without A-192621 improved the aforementioned cardiac dysfunction, to the same extent. Norepinephrine was massively released in coronary effluent from the hearts exposed to ischemia/ reperfusion. Treatment with ABT-627 significantly suppressed the norepinephrine overflow induced by the ischemia/reperfusion whereas A-192621 further enhanced it, which was completely abolished by the concomitant treatment with ABT-627. These results suggest that the detrimental effect of ETB receptor blockade on post-ischemic cardiac function is mediated by the ETA receptor-related action and that norepinephrine overflow from sympathetic nerve endings is closely related to the antagonist-induced functional changes of post-ischemic hearts.

Topics: Animals; Atrasentan; Cardiovascular Agents; Coronary Circulation; Drug Therapy, Combination; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; In Vitro Techniques; Male; Myocardial Reperfusion Injury; Myocardium; Norepinephrine; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; Receptor, Endothelin B; Sympathetic Nervous System; Time Factors; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Pressure

Topics: Aortic Valve Insufficiency; Cardiovascular Agents; Chronic Disease; Humans; Hypertrophy, Left Ventricular; Practice Guidelines as Topic; Systole; United States; Ventricular Dysfunction, Left

The present study examined the ability of dual-chamber (DDD) pacing to improve symptoms and exercise tolerance in patients with non-obstructive hypertrophic cardiomyopathy (HNCM). Seven patients with HNCM who had failed to benefit from pharmacotherapy participated in the study. The New York Heart Association (NHYA) functional class status and exercise tolerance, which was determined by the treadmill exercise test, were recorded and an echocardiographic observation was performed before, and 1 week, 3 months and 1 year after the implantation of a permanent DDD pacemaker. The atrioventricular delay (AVd) was determined by measuring the point of peak rapid filling velocity and maximum cardiac output (CO). Two patients were not implanted with a permanent pacemaker because their CO and blood pressure decreased or because palpitation occurred during temporary pacing. The ratio between early and late peaks of flow velocity (1.56, 1.21,0.95, and 0.86 before implantation and 1 week, 3 months and 1 year after implantation, respectively); deceleration time (ms: 263.2, 217.6, 204.6, 187.0); peak filling rate (ml/s: 146.2, 204.0, 233.2, 243.6); NYHA functional class status (2.0, 1.8, 1.6, 1.4); and exercise tolerance (s: 203, 264, 403, 480) were significantly improved after implantation. However, left ventricular dimension, percent fractional shortening, ejection fraction, acceleration time and the isovolumic relaxation time were not changed significantly. In conclusion, DDD pacing improved symptoms and the NYHA functional class status, which is associated with improvement of left ventricular diastolic function. It is proposed that DDD pacing would be useful in patients not only with obstructive but also non-obstructive hypertrophic cardiomyopathy refractory to medical treatment, depending on the careful selection of subjects.

Topics: Aged; Cardiac Pacing, Artificial; Cardiovascular Agents; Diastole; Drug Resistance; Echocardiography; Echocardiography, Doppler; Exercise Test; Exercise Tolerance; Female; Follow-Up Studies; Heart Failure; Heart Ventricles; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Severity of Illness Index; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Pressure

Topics: Blood Chemical Analysis; Cardiovascular Agents; Drug Therapy, Combination; Humans; Monitoring, Ambulatory; Point-of-Care Systems; Ventricular Dysfunction, Left

Topics: Accidents, Home; Adult; Anticoagulants; Antithrombin III Deficiency; Arginine; Burns; Cardiovascular Agents; Coronary Vasospasm; Debridement; Drug Therapy, Combination; Explosions; Humans; Male; Pipecolic Acids; Sulfonamides; Ventricular Dysfunction, Left; Warfarin

Peripartum cardiomyopathy (PPCM) is a rare life-threatening cardiomyopathy of unknown cause that occurs in the peripartum period in previously healthy women. In April 1997, the National Heart, Lung, and Blood Institute (NHLBI) and the Office of Rare Diseases of the National Institutes of Health (NIH) convened a Workshop on Peripartum Cardiomyopathy to foster a systematic review of information and to develop recommendations for research and education.. Fourteen workshop participants were selected by NHLBI staff and represented cardiovascular medicine, obstetrics, immunology, and pathology. A representative subgroup of 8 participants and NHLBI staff formed the writing group for this article and updated the literature on which the conclusions were based. The workshop was an open meeting, consistent with NIH policy.. Data presented at the workshop were augmented by a MEDLINE search for English-language articles published from 1966 to July 1999, using the terms peripartum cardiomyopathy, cardiomyopathy, and pregnancy. Articles on the epidemiology, pathogenesis, pathophysiology, diagnosis, treatment, and prognosis of PPCM were included. RECOMMENDATION PROCESS: After discussion of data presented, workshop participants agreed on a standardized definition of PPCM, a general clinical approach, and the need for a registry to provide an infrastructure for future research.. Peripartum cardiomyopathy is a rare lethal disease about which little is known. Diagnosis is confined to a narrow period and requires echocardiographic evidence of left ventricular systolic dysfunction. Symptomatic patients should receive standard therapy for heart failure, managed by a multidisciplinary team. If subsequent pregnancies occur, they should be managed in collaboration with a high-risk perinatal center. Systematic data collection is required to answer important questions about incidence, treatment, and prognosis.

Topics: Cardiomyopathies; Cardiovascular Agents; Congresses as Topic; Echocardiography; Female; Humans; Incidence; National Institutes of Health (U.S.); Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Trimester, Third; Pregnancy, High-Risk; Prognosis; Puerperal Disorders; Risk Factors; United States; Ventricular Dysfunction, Left

The objective of this study was to determine how subgroup analyses are performed in large randomized trials of cardiovascular pharmacotherapy.. We reviewed 67 randomized, double-blind, controlled trials involving pharmacotherapy in at least 1000 patients with unstable angina, myocardial infarction, left ventricular dysfunction, or heart failure with clinical outcomes as primary end points, published between 1980 and 1997. Nine had no subgroup analyses but 43 reported on 5 or more subgroups and 31 reported subgroups without formal statistical tests for treatment-subgroup interactions. In most trials, a rationale for subgroup selection was missing. All but 6 focused on single-factor subgroups.. Trial subgroups should ideally be defined a priori on 2 bases: single-factor subgroups with a strong rationale for biological response modification and multifactorial prognostic subgroups defined from baseline risks. However, single-factor subgroup analyses are often reported without a supporting rationale or formal statistical tests for interactions. We suggest that clinicians should interpret published subgroup-specific variations in treatment effects skeptically unless there is a prespecified rationale and a significant treatment-subgroup interaction.

Topics: Angina, Unstable; Cardiovascular Agents; Data Interpretation, Statistical; Double-Blind Method; Heart Failure; Humans; Myocardial Infarction; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Assessment; Treatment Outcome; Ventricular Dysfunction, Left

The aim of the study was to verify the prognostic implications of viability detection using baseline-nitrate sestamibi imaging in patients with left ventricular (LV) dysfunction due to chronic coronary artery disease (CAD) submitted to different therapeutic strategies.. The prognostic meaning of preserved viability in these patients is still debated. Sestamibi is increasingly used for myocardial perfusion scintigraphy and is being accepted also as viability tracer, but no data are available about the relationship between viability in sestamibi imaging, subsequent treatment, and patient's outcome.. Follow-up data were collected in 105 CAD patients with LV dysfunction who had undergone baseline-nitrate sestamibi perfusion imaging for viability assessment and had been later treated medically (group 1), or submitted to revascularization, which was either complete (group 2A) or incomplete (group 2B).. Eighteen hard events (cardiac death or nonfatal myocardial infarction) were registered during the follow-up. A significantly worse event-free survival curve was observed in the patients of group 1 (p < 0.0002) and group 2B (p < 0.03) compared to those of group 2A. Using a Cox proportional hazard model, the most powerful prognostic predictors of events were the number of nonrevascularized asynergic segments with viability in sestamibi imaging (p < 0.003, risk ratio [RR] = 1.4), and the severity of CAD (p < 0.02, RR = 1.28).. Viability detection in sestamibi imaging has important prognostic implications in CAD patients with LV dysfunction. Patients with preserved viability kept on medical therapy or submitted to incomplete revascularization represent high-risk groups.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chronic Disease; Coronary Disease; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Revascularization; Nitrates; Prognosis; Radiopharmaceuticals; Technetium Tc 99m Sestamibi; Tissue Survival; Tomography, Emission-Computed, Single-Photon; Ventricular Dysfunction, Left

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Cardiovascular Agents; Diuretics; Drug Prescriptions; Female; Heart Failure; Humans; Male; Middle Aged; Registries; Severity of Illness Index; Sex Factors; Systole; Ventricular Dysfunction, Left

Endothelial dysfunction and effectiveness of treatment of calcium antagonists are suggestive of coronary artery spasm as an underlying disorder in dilated cardiomyopathy (DCM). The aim of this study is to determine whether or not the epicardial coronary artery spasm can induce severe cardiac dysfunction like DCM. Thirty-four consecutive patients with angiographically normal coronary arteries and diffuse left ventricular hypokinesis whose causes had been unknown underwent acetylcholine provocation test and left ventricular biopsy. Eight patients were excluded according to the clinical and laboratory data and biopsy findings suggesting myocarditis or other systemic diseases. According to the results of the acetylcholine provocation test, 17 patients were finally diagnosed as having DCM, and nine patients (35% of the study patients), who had acetylcholine-induced diffuse and multivessel coronary spasm, were diagnosed as having DCM-like vasospastic angina pectoris (VSA). Clinical and cardiac catheterization data including hemodynamics and biopsy findings were similar between the two groups except that left ventricular end-systolic volume was significantly greater in DCM than in DCM-like VSA. After the acetylcholine provocation test, DCM patients received both a beta blocker and an angiotensin-converting enzyme inhibitor, and DCM-like VSA patients received antianginal drugs. In echocardiographic findings at predischarge and those after 6-month drug treatment, both DCM-lke VSA and DCM showed significant reduction in end-diastolic and end-systolic diameters and significant increase in fractional shortening and ejection fraction, whereas changes in ejection fraction and fractional shortening were significantly greater in DCM-like VSA than those in DCM. Epicardial coronary artery spasm can induce diffuse and severe left ventricular dysfunction like DCM in VSA. Although antianginal drugs markedly improve left ventricular function of these patients, only the acetylcholine provocation test can identify DCM-like VSA.

Topics: Acetylcholine; Adult; Aged; Biopsy; Cardiac Catheterization; Cardiomyopathy, Dilated; Cardiovascular Agents; Coronary Angiography; Coronary Vasospasm; Endothelium, Vascular; Female; Heart Ventricles; Hemodynamics; Humans; Male; Middle Aged; Severity of Illness Index; Ventricular Dysfunction, Left

Ventricular tachyarrhythmias present a unique set of stimuli to arterial and cardiopulmonary baroreceptors by increasing cardiac filling pressures and decreasing arterial pressure. The net effect on the control of sympathetic nerve activity (SNA) in humans is unknown. The purpose of this study was to determine the relative roles of cardiopulmonary and arterial baroreceptors in controlling SNA and arterial pressure during ventricular pacing in humans.. Two experiments were performed in which SNA and hemodynamic responses to ventricular pacing were compared with nitroprusside infusion (NTP) in 12 patients and studied with and without head-up tilt or phenylephrine to normalize the stimuli to either the arterial or cardiopulmonary baroreceptors in 9 patients. In experiment 1, the slope of the relation between SNA and mean arterial pressure was greater during NTP (-4.7+/-1.4 U/mm Hg) than during ventricular pacing (-3.4+/-1.1 U/mm Hg). Comparison of NTP doses and ventricular pacing rates that produced comparable hypotension showed that SNA increased more during NTP (P=0.03). In experiment 2, normalization of arterial pressure during pacing resulted in SNA decreasing below baseline (P<0.05), whereas normalization of cardiac filling pressure resulted in a greater increase in SNA than pacing alone (212+/-35% versus 189+/-37%, P=0. 04). Conclusions--These data demonstrate that in humans arterial baroreflex control predominates in mediating sympathoexcitation during ventricular tachyarrhythmias and that cardiopulmonary baroreceptors contribute significant inhibitory modulation.

Topics: Action Potentials; Adult; Baroreflex; Blood Pressure; Cardiac Catheterization; Cardiac Pacing, Artificial; Cardiotonic Agents; Cardiovascular Agents; Humans; Middle Aged; Nitroprusside; Peroneal Nerve; Phenylephrine; Reflex, Abnormal; Sympathetic Nervous System; Tachycardia, Supraventricular; Tachycardia, Ventricular; Tilt-Table Test; Vasodilator Agents; Ventricular Dysfunction, Left

We examined the effects of MET-88 on haemodynamics and cardiac hypertrophy in rats with an aortocaval shunt (A-V shunt). On the day of surgery, an A-V shunt was produced by using an 18-gauge needle in Wistar rats as described by Garcia and Diebold. MET-88 and captopril were orally administered to rats 1 week after surgery, and the administration was continued for 3 weeks. Four weeks after the surgery, A-V shunt-operated rats had biventricular hypertrophy and higher right atrial pressure (RAP) and left ventricular end-diastolic pressure (LVEDP) than sham-operated rats. Compared with untreated A-V shunt rats, those treated with MET-88 showed significant attenuation of the development of left ventricular (LV) hypertrophy and of the increased LVEDP. Captopril-treated A-V shunt rats also failed to show increases in LV weight and LVEDP. In in vitro studies, MET-88 had no effect on renin and angiotensin-converting enzyme (ACE) activities in the plasma of normal rats. These results suggest that MET-88 improved LV hypertrophy and LV dysfunction in rats with an A-V shunt. Furthermore, the data indicate that the beneficial effects of MET-88 may be attributed to some pathway, not involving the renin-angiotensin system, such as myocardial energy metabolism, venous return, etc. We conclude that MET-88 may be a novel agent for the therapy of chronic heart failure.

Topics: Animals; Body Weight; Cardiac Volume; Cardiomegaly; Cardiovascular Agents; Heart; Hemodynamics; Male; Methylhydrazines; Organ Size; Peptidyl-Dipeptidase A; Rats; Rats, Wistar; Renin; Ventricular Dysfunction, Left

To determine whether subsets of patients referred for a clinically indicated radionuclide adenosine stress study respond differently to a standard infusion of adenosine.. We assessed multiple clinical and hemodynamic variables in the first 2,000 patients who underwent adenosine perfusion studies in our laboratory. A relevant clinical variable was defined as one that was significantly associated with changes in heart rate and blood pressure during adenosine infusion. Relevant clinical variables that were most significantly related to hemodynamic variables included age, gender, rhythm (atrial fibrillation), diabetes, and left ventricular function. These variables were then related to symptomatic responses (adverse effects) to adenosine infusion. To determine whether the different peripheral responses to adenosine reflected clinically important differences in coronary vasodilatation, we compared perfusion imaging with coronary angiographic findings in the 408 patients who underwent both studies within 6 months of each other.. The decrease in systolic blood pressure was greater and the reflex tachycardia was less in patients 70 years of age or older and in those with insulin-dependent diabetes in comparison with younger patients and those without type 1 diabetes. Men had smaller decreases in blood pressure and smaller increases in heart rate than did women. Patients with atrial fibrillation and those with left ventricular ejection fraction less than 40% had smaller decreases in blood pressure and smaller increases in heart rate than did those in sinus rhythm or those with an ejection fraction of 40% or more. Age 70 years or older, male gender, atrial fibrillation, and left ventricular ejection fraction less than 40% were associated with fewer symptoms and less severe chest pain in comparison with patients without these variables. For patients with coronary angiograms, the relationship between coronary artery disease evident on angiography and perfusion abnormalities noted on scintigraphy was not different for any of the relevant clinical variables.. Common clinical patient subsets are associated with different peripheral hemodynamic and symptomatic responses to infusion of adenosine. Despite these observations, however, the ability to detect coronary artery disease with perfusion imaging is not obviously altered.

Topics: Adenosine; Age Factors; Aged; Atrial Fibrillation; Cardiovascular Agents; Coronary Angiography; Diabetes Mellitus, Type 1; Female; Hemodynamics; Humans; Linear Models; Logistic Models; Male; Multivariate Analysis; Retrospective Studies; Sex Factors; Tomography, Emission-Computed, Single-Photon; Ventricular Dysfunction, Left

Topics: Attitude of Health Personnel; Cardiovascular Agents; Clinical Protocols; Coronary Artery Bypass; Heart Failure; Humans; Randomized Controlled Trials as Topic; Research Design; Sensitivity and Specificity; Survival Rate; Treatment Outcome; Ventricular Dysfunction, Left

We sought to assess whether in clinically stable patients with chronic heart failure (CHF) the prolongation (i.e., increase) of an initially short (< or = 125 ms) Doppler transmitral deceleration time (DT) of early filling obtained with long-term optimal oral therapy predicts a more favorable prognosis.. It has been recently demonstrated that transmitral early DT is a powerful independent predictor of poor prognosis in patients with left ventricular dysfunction. However, DT may change over time according to loading conditions and medical treatment.. One hundred forty-four patients with CHF and a short DT (< or = 125 ms) underwent repeat Doppler echocardiographic study 6 months after the initial examination, while clinically stable with optimal oral therapy, and were then followed up for a mean period of 26 +/- 7 months.. After 6 months, DT had not changed in 80 patients (group 1), whereas it was significantly prolonged (> 125 ms) in the remaining 64 patients (group 2). Baseline Doppler echocardiographic features were similar in the two groups. No changes were found after 6 months in group 1, whereas group 2 showed a slight but significant (p < 0.01) reduction in end-systolic volume, an improvement in left ventricular ejection fraction (p < 0.01) and a decrease (p < 0.01) in the degree of tricuspid regurgitation. During follow-up, 37% of patients in group 1 experienced cardiac death versus 11% in group 2 (p < 0.0005). By Cox model analysis, prolongation of a short DT emerged as the single best predictor of survival (chi-square 15.70).. The prolongation of an initially short DT obtained with long-term optimal oral therapy predicts a more favorable outcome in clinically stable patients with CHF.

Topics: Cardiovascular Agents; Diastole; Echocardiography, Doppler; Female; Heart Failure; Humans; Male; Middle Aged; Mitral Valve; Multivariate Analysis; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Prospective Studies; Regional Blood Flow; Treatment Outcome; Ventricular Dysfunction, Left

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

Angiotensin-converting enzyme (ACE) inhibition as well as neutral endopeptidase (NEP) inhibition was demonstrated to influence hemodynamics in various cardiac disease states. However, specific effects of chronic combined ACE and NEP inhibition on left ventricular (LV) and myocyte geometry and function remain unclear. In this study, a dual-acting metalloprotease inhibitor (DMPI), which possesses both ACE and NEP inhibitory activity, was used in a rapid-pacing model of LV dysfunction. LV and myocyte geometry and function were examined in control dogs (n = 6), in dogs with pacing-induced LV dysfunction (216 +/- 2 beats/min, 28 days, n = 7), and in dogs with DMPI treatment during rapid pacing (10 mg/kg p.o., b.i.d., n = 6). With chronic rapid pacing, LV end-diastolic volume increased (84 +/- 4 vs. 49 +/- 3 ml), and LV ejection fraction decreased (38 +/- 3% vs. 68 +/- 3%) compared with control (p < 0.05). DMPI concomitantly administered during long-term rapid pacing did not change LV ejection fraction (35 +/- 3%), but LV end-diastolic volume was reduced (70 +/- 5 vs. 84 +/- 4 ml; p < 0.05) when compared with rapid pacing only. With long-term rapid pacing, myocyte cross-sectional area was decreased (278 +/- 5 vs. 325 +/- 5 microm2), and resting length increased (178 +/- 2 vs. 152 +/- 1 microm) when compared with control (p < 0.05). With DMPI concomitantly administered during rapid pacing, myocyte cross-sectional area (251 +/- 5 microm2) and resting length (159 +/- 4 microm) were reduced when compared with rapid pacing only (p < 0.05). Myocyte velocity of shortening decreased from control values with long-term rapid pacing (39.3 +/- 3.9 vs. 73.2 +/- 5.9 microm/s; p < 0.05) but improved with DMPI treatment during rapid pacing when compared with rapid pacing only (58.9 +/- 6.7 microm/s; p < 0.05). Myocyte velocity of shortening with beta-adrenergic-receptor stimulation (25 nM isoproterenol) was reduced from controls with rapid pacing (125 +/- 12 vs. 214 +/- 30 microm/s; p < 0.05) but was improved with DMPI treatment during rapid pacing when compared with rapid pacing only (178 +/- 12 microm/s; p < 0.05). In a model of rapid pacing-induced LV failure, concomitant DMPI treatment significantly reduced the degree of LV dilation with no apparent effect on LV pump function. At the level of the LV myocyte, long-term DMPI treatment with rapid pacing improved myocyte performance and beta-adrenergic response. Thus the improvement in isolated myocyte contractile function was

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiovascular Agents; Dogs; Enzyme Inhibitors; Female; Hormones; Male; Metalloendopeptidases; Myocardial Contraction; Myocardium; Neprilysin; Peptidyl-Dipeptidase A; Pyridines; Receptors, Adrenergic, beta; Thiazepines; Ventricular Dysfunction, Left

Topics: Cardiovascular Agents; Humans; Hypertension; Hypertrophy, Left Ventricular; Ventricular Dysfunction, Left

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