cardiovascular-agents and Heart-Diseases

The notion that poikilotherms do not suffer from cardiovascular conditions is being increasingly challenged as diagnostic tools used in companion animal practice are applied to reptiles. However, the cause, diagnosis, and treatment of cardiac conditions in reptiles is difficult because of the scarcity of published literature. Auscultation, electrocardiography, radiography, and ultrasonography are helpful diagnostic techniques in herpetologic practice. Although the pharmacokinetics and pharmacodynamics of cardiovascular drugs are poorly understood in these animals, basic principles remain applicable; these include pharmacologic and nonpharmacologic interventions. Further research is needed to establish species-specific cardiac reference ranges and evidence-based treatment options.

Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Heart Diseases; Reptiles

Mitochondria have been recognized as key organelles in cardiac physiology and are potential targets for clinical interventions to improve cardiac function. Mitochondrial dysfunction has been accepted as a major contributor to the development of heart failure. The main function of mitochondria is to meet the high energy demands of the heart by oxidative metabolism. Ionic homeostasis in mitochondria directly regulates oxidative metabolism, and any disruption in ionic homeostasis causes mitochondrial dysfunction and eventually contractile failure. The mitochondrial ionic homeostasis is closely coupled with inner mitochondrial membrane potential. To regulate and maintain ionic homeostasis, mitochondrial membranes are equipped with ion transporting proteins. Ion transport mechanisms involving several different ion channels and transporters are highly efficient and dynamic, thus helping to maintain the ionic homeostasis of ions as well as their salts present in the mitochondrial matrix. In recent years, several novel proteins have been identified on the mitochondrial membranes and these proteins are actively being pursued in research for roles in the organ as well as organelle physiology. In this article, the role of mitochondrial ion channels in cardiac function is reviewed. In recent times, the major focus of the mitochondrial ion channel field is to establish molecular identities as well as assigning specific functions to them. Given the diversity of mitochondrial ion channels and their unique roles in cardiac function, they present novel and viable therapeutic targets for cardiac diseases.

Topics: Animals; Cardiovascular Agents; Energy Metabolism; Heart Diseases; Humans; Ion Transport; Membrane Potential, Mitochondrial; Mitochondria, Heart; Mitochondrial Membrane Transport Proteins; Myocytes, Cardiac

The patient cohort with left ventricular ejection fractions (LVEFs) of 41%-49%, which has been defined as heart failure with midrange ejection fraction (HFmrEF), represent a significant proportion of the heart failure (HF) population. Despite the clear cutoffs established by different society guidelines, confusion remains regarding the exact significance of midrange LVEF within the HF syndrome. Patients with LVEF 41%-49% represent a heterogeneous group of patients sharing pathophysiologic mechanisms, biomarker profiles, comorbidities, and clinical characteristics with patients with preserved and reduced LVEF. In this clinical review, we discuss the underlying pathophysiologic mechanisms that culminate in the clinical syndrome of HF and contribute to the disparities observed between HFpEF, HFrEF, and HFmrEF. We highlight differences and similarities in clinical characteristics and imaging features between HFpEF and HFrEF in an effort to disentangle the heterogeneous group of patients with midrange LVEF, but ultimately we conclude that LVEF should be seen as simply one important element of a continuum throughout the HF syndrome, and that although is useful, it is an oversimplification, because HF syndrome is more of a continuum. The underlying pathophysiology, etiology, and comorbidities of patients presenting with HF is becoming ever more important as the limitations of a classification solely based on LVEF are being better recognised, and as patient-specific personalisation of care is becoming ever more important.

Topics: Cardiovascular Agents; Clinical Trials as Topic; Echocardiography; Heart Diseases; Heart Failure; Humans; Magnetic Resonance Imaging, Cine; Stroke Volume; Vascular Remodeling

The development of organs-on-chip (OoC) has revolutionized in vitro cell-culture experiments by allowing a better mimicry of human physiology and pathophysiology that has consequently led researchers to gain more meaningful insights into disease mechanisms. Several models of hearts-on-chips and vessels-on-chips have been demonstrated to recapitulate fundamental aspects of the human cardiovascular system in the recent past. These 2D and 3D systems include synchronized beating cardiomyocytes in hearts-on-chips and vessels-on-chips with layer-based structures and the inclusion of physiological and pathological shear stress conditions. The opportunities to discover novel targets and to perform drug testing with chip-based platforms have substantially enhanced, thanks to the utilization of patient-derived cells and precise control of their microenvironment. These organ models will provide an important asset for future approaches to personalized cardiovascular medicine and improved patient care. However, certain technical and biological challenges remain, making the global utilization of OoCs to tackle unanswered questions in cardiovascular science still rather challenging. This review article aims to introduce and summarize published work on hearts- and vessels-on chips but also to provide an outlook and perspective on how these advanced in vitro systems can be used to tailor disease models with patient-specific characteristics.

Topics: Animals; Cardiovascular Agents; Cell Culture Techniques; Cells, Cultured; Clinical Decision-Making; Drug Development; Drug Discovery; Heart Diseases; Humans; Lab-On-A-Chip Devices; Microfluidic Analytical Techniques; Myocytes, Cardiac; Precision Medicine

Human induced pluripotent stem cells (hiPSCs) have emerged as a promising platform for pharmacogenomics and drug development. In cardiology, they make it possible to produce unlimited numbers of patient-specific human cells that reproduce hallmark features of heart disease in the culture dish. Their potential applications include the discovery of mechanism-specific therapeutics, the evaluation of safety and efficacy in a human context before a drug candidate reaches patients, and the stratification of patients for clinical trials. Although this new technology has the potential to revolutionize drug discovery, translational hurdles have hindered its widespread adoption for pharmaceutical development. Here we discuss recent progress in overcoming these hurdles that should facilitate the use of hiPSCs to develop new medicines and individualize therapies for heart disease.

Topics: Cardiovascular Agents; Drug Development; Heart Diseases; Humans; Induced Pluripotent Stem Cells

Although cardiac diseases such as acute myocardial infarction, heart failure and arrhythmias are the leading cause of cardiovascular complications in rheumatoid arthritis (RA), their pathogenesis is far from being understood and optimal therapeutic options to treat specifically these disorders in RA are lacking. Preclinical studies on animal models of arthritis can help to decipher the complex link between arthritis and the heart, and to identify critical pathways and novel therapeutic targets. This review presented the available data on cardiac disorders in animal models of RA, as well as the current knowledge on pathophysiology and pharmacology of these disorders. Future directions for translational studies in a cardiorheumatic perspective are proposed.

Topics: Animals; Antirheumatic Agents; Arthritis, Rheumatoid; Cardiovascular Agents; Disease Models, Animal; Heart Diseases; Humans; Inflammation Mediators; Joints; Myocardium; Oxidative Stress

Cyclic nucleotide phosphodiesterases comprise an 11-member superfamily yielding near 100 isoform variants that hydrolyze cAMP or cGMP to their respective 5'-monophosphate form. Each plays a role in compartmentalized cyclic nucleotide signaling, with varying selectivity for each substrate, and conveying cell and intracellular-specific localized control. This review focuses on the 5 phosphodiesterases (PDEs) expressed in the cardiac myocyte capable of hydrolyzing cGMP and that have been shown to play a role in cardiac physiological and pathological processes. PDE1, PDE2, and PDE3 catabolize cAMP as well, whereas PDE5 and PDE9 are cGMP selective. PDE3 and PDE5 are already in clinical use, the former for heart failure, and PDE1, PDE9, and PDE5 are all being actively studied for this indication in patients. Research in just the past few years has revealed many novel cardiac influences of each isoform, expanding the therapeutic potential from their selective pharmacological blockade or in some instances, activation. PDE1C inhibition was found to confer cell survival protection and enhance cardiac contractility, whereas PDE2 inhibition or activation induces beneficial effects in hypertrophied or failing hearts, respectively. PDE3 inhibition is already clinically used to treat acute decompensated heart failure, although toxicity has precluded its long-term use. However, newer approaches including isoform-specific allosteric modulation may change this. Finally, inhibition of PDE5A and PDE9A counter pathological remodeling of the heart and are both being pursued in clinical trials. Here, we discuss recent research advances in each of these PDEs, their impact on the myocardium, and cardiac therapeutic potential.

Topics: Animals; Cardiovascular Agents; Cyclic GMP; Heart Diseases; Humans; Myocardium; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Second Messenger Systems

Ivabradine lowers heart rate (HR) without affecting contractility or vascular tone. It is licensed for HR control in chronic heart diseases. We performed a systematic review and meta-analyses to examine whether ivabradine could decrease major adverse cardiovascular events (MACE) and mortality in critically ill patients.. We searched Medline, Embase, Cochrane Library, and Web of Science for RCTs. Trial quality was assessed using the Cochrane risk of bias tool. Random-effects meta-analyses were performed if at least three trials or 100 patients were available. Results are reported as weighted mean difference (WMD), odds ratio (OR), and 95% confidence intervals (CIs). Trial sequential analyses were performed to estimate the sample size needed to reach definitive conclusions of efficacy or futility.. We included 13 RCTs (n=1497 patients). We found no evidence of an impact of ivabradine on MACE (three RCTs, 819 patients; OR=0.77; 95% CI, 0.53-1.11) or mortality (10 RCTs, 1356 patients; OR=1.07; 95% CI, 0.63-1.82), but sample sizes were not reached to allow definitive conclusions. Compared with placebo or standard care, ivabradine reduced HR (eight RCTs, 464 patients; WMD, -9.5 beats min. Ivabradine reduces HR compared with placebo or standard care. The effect on MACE or mortality in acute care remains unclear. Further RCTs powered to detect changes in clinically relevant outcomes are warranted.. Prospero CRD42018086109.

Topics: Cardiovascular Agents; Critical Illness; Heart Diseases; Humans; Ivabradine; Treatment Outcome

The 3',5'-cyclic guanosine monophosphate (cGMP)-dependent protein kinase type I (cGKI aka PKGI) is a major cardiac effector acting downstream of nitric oxide (NO)-sensitive soluble guanylyl cyclase and natriuretic peptides (NPs), which signal through transmembrane guanylyl cyclases. Consistent with the wide distribution of the cGMP-generating guanylyl cyclases, cGKI, which usually elicits its cellular effects by direct phosphorylation of its targets, is present in multiple cardiac cell types including cardiomyocytes (CMs). Although numerous targets of cGMP/cGKI in heart were identified in the past, neither their exact patho-/physiological functions nor cell-type specific roles are clear. Herein, we inform about the current knowledge on the signal transduction downstream of CM cGKI. We believe that better insights into the specific actions of cGMP and cGKI in these cells will help to guide future studies in the search for predictive biomarkers for the response to pharmacological cGMP pathway modulation. In addition, targets downstream of cGMP/cGKI may be exploited for refined and optimized diagnostic and therapeutic strategies in different types of heart disease and their causes. Importantly, key functions of these proteins and particularly sites of regulatory phosphorylation by cGKI should, at least in principle, remain intact, although upstream signaling through the second messenger cGMP is impaired or dysregulated in a stressed or diseased heart state.

Topics: Animals; Cardiovascular Agents; Cyclic GMP; Cyclic GMP-Dependent Protein Kinase Type I; Heart Diseases; Humans; Myocytes, Cardiac; Phosphorylation; Second Messenger Systems; Substrate Specificity

Buyang Huanwu Decoction (BHD) is a multi-herbal composition commonly prescribed in the treatment of cerebrovascular diseases such as stroke. Although studies have been conducted at the cellular (in vitro), animal and human (in vivo) level, there was no detailed analysis on how the composition and proportion of BHD is modified according to target diseases.. The purpose of this study is to investigate the composition and proportion of each herb in BHD to summarize how the original BHD was modified according to the target disease.. Electronic literature searches were performed in three databases, collecting sixty-eight studies for the final analysis. The studies were divided into three types: cell studies, animal experiments and clinical trial. In the analysis, the decoction formula including the composition and the weight proportion of the herbs in BHD used in the studies and the target diseases were examined.. The result showed that in cell studies, the targets were mostly cell differentiation, cell injury and immune activation. In animal studies, cerebrovascular diseases such as cerebral ischemia were the most identified target diseases followed by nervous system and cardiovascular diseases. While the proportions of the herbs in BHD used in these studies were in general similar to the original formula, some studies reduced the amount of Astragali Radix to half of the original amount. Modified BHDs were used in four studies for cerebrovascular and peripheral nerve diseases. However, no significant correlation has been observed between the target diseases and the change of the proportion of the herbs in BHD.. The most commonly used formula was the original composition of BHD, and modified BHDs were reported to be used to treat cerebrovascular and nervous diseases. Further studies about the effects of BHD by composition and proportion of herbs are needed in the future.

Topics: Animals; Cardiovascular Agents; Cerebrovascular Disorders; Drug Compounding; Drugs, Chinese Herbal; Heart Diseases; Humans; Neuroprotective Agents; Peripheral Nervous System Diseases

Cardiovascular system cell biology is tightly regulated and mitochondria play a relevant role in maintaining heart function. In recent decades, associations between such organelles and the sarco/endoplasmic reticulum (SR) have been raised great interest. Formally identified as mitochondria-associated SR membranes (MAMs), these structures regulate different cellular functions, including calcium management, lipid metabolism, autophagy, oxidative stress, and management of unfolded proteins. In this review, we highlight MAMs' alterations mainly in cardiomyocytes, linked with cardiovascular diseases, such as cardiac ischemia-reperfusion, heart failure, and dilated cardiomyopathy. We also describe proteins that are part of the MAMs' machinery, as the FUN14 domain containing 1 (FUNDC1), the sigma 1 receptor (Sig-1R) and others, which might be new molecular targets to preserve the function and structure of the heart in such diseases. Understanding the machinery of MAMs and its function demands our attention, as such knowledge might contribute to strengthen the role of these relative novel structures in heart diseases.

Topics: Animals; Calcium Signaling; Cardiovascular Agents; Endoplasmic Reticulum; Heart Diseases; Humans; Membrane Proteins; Mitochondria, Heart; Mitochondrial Membranes; Mitochondrial Proteins; Myocytes, Cardiac; Receptors, sigma; Sigma-1 Receptor

Comorbidity between epilepsy and heart diseases is frequent.. All drugs classified within the group of drugs for cardiovascular system according to the Anatomical Therapeutic Chemical (ATC) classification system were reviewed for their effects on seizures or epilepsy.. Several agents showed antiseizure properties in animal models of seizures and/or in patients with epilepsy and only few were proconvulsant. Drugs with anticonvulsant effects include mecamylamine and guanfacine (antihypertensive drugs), indapamide, amiloride, furosemide and bumetanide (diuretics), fasudil (peripheral vasodilator), bioflavonoids (vasoprotective drug), propranolol (beta blocking agent), isradipine, nimodipine, verapamil and diltiazem (calcium channel blockers: CCBs), fosinopril and zofenopril (agents acting on the renin-angiotensin system), several statins, and fenofibrate (lipid-modifying agents). Drugs with proconvulsant properties in experimental models or in patients include reserpine, buflomedil, naftidrofuryl, and clonidine and propranolol at high doses. Drug-drug interactions (DDI) between antiseizure medications (ASMs) and drugs for cardiovascular system were also searched in two leading publicly accessible drug compendia. The most important DDIs occur between enzyme-inducing (EI) ASMs and ivabradine, ranolazine, macitenan and between EI-ASMs and the CCBs felodipine, nicardipine, nisoldipine, and verapamil. Simvastatin and atorvastatin are the lipid-modifying agents with more DDIs with EI-ASMs. Several pharmacodynamic interactions have been also documented.. Available data show that the treatment of patients with epilepsy and vascular comorbidities is challenging and requires the appropriate knowledge of pharmacological properties of drugs and drug interactions.

Topics: Animals; Anticonvulsants; Cardiovascular Agents; Drug Interactions; Epilepsy; Heart Diseases; Humans

Cardiac injury may have multiple causes, including ischaemic, non-ischaemic, autoimmune, and infectious triggers. Independent of the underlying pathophysiology, cardiac tissue damage induces an inflammatory response to initiate repair processes. Immune cells are recruited to the heart to remove dead cardiomyocytes, which is essential for cardiac healing. Insufficient clearance of dying cardiomyocytes after myocardial infarction (MI) has been shown to promote unfavourable cardiac remodelling, which may result in heart failure (HF). Although immune cells are integral key players of cardiac healing, an unbalanced or unresolved immune reaction aggravates tissue damage that triggers maladaptive remodelling and HF. Neutrophils and macrophages are involved in both, inflammatory as well as reparative processes. Stimulating the resolution of cardiac inflammation seems to be an attractive therapeutic strategy to prevent adverse remodelling. Along with numerous experimental studies, the promising outcomes from recent clinical trials testing canakinumab or colchicine in patients with MI are boosting the interest in novel therapies targeting inflammation in cardiovascular disease patients. The aim of this review is to discuss recent experimental studies that provide new insights into the signalling pathways and local regulators within the cardiac microenvironment promoting the resolution of inflammation and tissue regeneration. We will cover ischaemia- and non-ischaemic-induced as well as infection-related cardiac remodelling and address potential targets to prevent adverse cardiac remodelling.

Topics: Angiogenic Proteins; Animals; Cardiovascular Agents; Extracellular Matrix; Fibroblasts; Heart Diseases; Humans; Immunologic Factors; Inflammation Mediators; Myocardium; Signal Transduction; Ventricular Function, Left; Ventricular Remodeling

Beta-adrenergic receptors are expressed in cardiomyocytes and activated by either noradrenaline released from sympathetic synapses or circulating catecholamines. Their corresponding receptors have three subtypes, namely, β1, β2 and β3, which are members of the G protein-coupled receptors (GPCRs) family. Activation of β1-adrenergic receptors causes various physiological reactions including cardiac contraction and renin secretion from juxtaglomerular cells of the kidney. Antagonists of β-adrenergic receptors, known as β-blockers, have been used effectively for over four decades and have beneficial effects in the treatment of cardiovascular diseases. There are three generations of β-blockers according to their pharmacological properties. Firstgeneration β-blockers are non-selective, blocking both β1- and β2-receptors; second-generation β- blockers are more cardioselective in that they are more selective for β1-receptors; and thirdgeneration β-blockers are highly selective drugs for β1-receptors. The latter also display vasodilator actions by blocking α1-adrenoreceptors and activating β3-adrenergic receptors. In addition, thirdgeneration β-blockers exhibit angiogenic, antioxidant, anti-proliferative, anti-hypertrophic and antiapoptotic activities among other effects that are still under investigation.. The objective of this review is to describe the evolution observed during the development of the three distinctive generations, thereby highlighting the advantages of third-generation β- blockers over the other two drug classes.

Topics: Adrenergic beta-Antagonists; Animals; Cardiovascular Agents; Heart Diseases; Humans; Myocytes, Cardiac; Receptors, Adrenergic, beta; Signal Transduction; Treatment Outcome

The lymphatic vasculature, which accompanies the blood vasculature in most organs, is indispensable in the maintenance of tissue fluid homeostasis, immune cell trafficking, and nutritional lipid uptake and transport, as well as in reverse cholesterol transport. In this Review, we discuss the physiological role of the lymphatic system in the heart in the maintenance of cardiac health and describe alterations in lymphatic structure and function that occur in cardiovascular pathology, including atherosclerosis and myocardial infarction. We also briefly discuss the role that immune cells might have in the regulation of lymphatic growth (lymphangiogenesis) and function. Finally, we provide examples of how the cardiac lymphatics can be targeted therapeutically to restore lymphatic drainage in the heart to limit myocardial oedema and chronic inflammation.

Topics: Animals; Cardiovascular Agents; Heart; Heart Diseases; Humans; Lymphangiogenesis; Lymphatic Vessels; Myocardium

Topics: Attitude of Health Personnel; Cardiologists; Cardiovascular Agents; Congresses as Topic; Education, Medical, Continuing; Guideline Adherence; Health Care Sector; Health Knowledge, Attitudes, Practice; Heart Diseases; Humans; Interdisciplinary Communication; Medication Adherence; Practice Guidelines as Topic; Practice Patterns, Physicians'; Radiologists; Societies, Medical; Stakeholder Participation

Transient receptor potential (TRP) channels are nonselective cationic channels that are generally Ca

Topics: Action Potentials; Animals; Cardiovascular Agents; Fibroblasts; Heart Diseases; Humans; Molecular Targeted Therapy; Myocytes, Cardiac; Purkinje Fibers; Signal Transduction; Sinoatrial Node; Transient Receptor Potential Channels

Many cardiac therapeutics lack significant evidence of benefit in the horse, and in many cases their use is based on extrapolation of evidence from other species. In recent years there has been a push to develop a better understanding of both the pharmacodynamics and pharmacokinetics of these drugs. Recent data have described the use of antiarrhythmic agents including sotalol, flecainide, and amiodarone. Data about the use of ACE inhibitors in the management of congestive heart failure are encouraging and support their use in certain cases, wheras evidence for other medicines, such as pimobendan, remain speculative.

Topics: Animals; Cardiovascular Agents; Heart Diseases; Horse Diseases; Horses

Severe postoperative complications can affect cardiac surgery patients. Levosimendan is a novel calcium sensitizer commonly administered after cardiac surgery. However, the patient benefits are controversial. PubMed, Embase, and the Cochrane library were systematically searched for randomized controlled trials comparing levosimendan with control in adult cardiac surgery patients. Twenty-five studies (3247 patients) were included. Pooled data indicated that levosimendan reduced mortality after cardiac surgery [odds ratio (OR) 0.63, 95% confidence interval (CI): 0.47-0.84, P = 0.001]. However, this reduction was restricted to patients with low (<50%) left ventricular ejection fraction (OR 0.49, 95% CI: 0.35-0.70, P = 0.0001). It significantly reduced the incidence of postoperative acute kidney injury (OR 0.55, 95% CI: 0.41-0.74, P < 0.0001) and renal replacement therapy use (OR 0.56, 95% CI: 0.39-0.80, P = 0.002). Moreover, levosimendan significantly shortened the duration of the intensive care unit stay (weighted mean differences -0.49 day, 95% CI: -0.75 to -0.24, P = 0.0002) and mechanical ventilation use (weighted mean differences -2.30 hours, 95% CI: -3.76 to -0.84, P = 0.002). In conclusion, levosimendan reduced the mortality in patients with low left ventricular ejection fraction and decreased the incidence of acute renal injury and renal replacement therapy use. In addition, it shortened the duration of the intensive care unit stay and mechanical ventilation use.

Topics: Acute Kidney Injury; Cardiac Surgical Procedures; Cardiovascular Agents; Drug Administration Schedule; Heart Diseases; Humans; Incidence; Intensive Care Units; Length of Stay; Perioperative Care; Renal Replacement Therapy; Respiration, Artificial; Risk Factors; Simendan; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

In recent decades, cardiovascular diseases have become the greatest health threat to human beings, and thus it is particularly important to explore the subtle underlying pathogenesis of cardiovascular diseases. Although many molecular pathways have been explored to be essential in the development of cardiovascular diseases, their clinical significances are still uncertain. With the emergence of induced pluripotent stem cells (iPSCs), a unique platform for cardiovascular diseases has been established to model cardiovascular diseases on specific genetic background in vitro. This review summarizes current progresses of iPSCs in cardiovascular disease modeling and drug testing. This review highlighted iPSC-based cardiovascular disease modeling and drug testing. The technical advances in iPSC-based researches and various clinically relevant applications are discussed. With further intensive research, iPSC technology will shape the future of clinical translational research in cardiovascular diseases.

Topics: Animals; Cardiotoxicity; Cardiovascular Agents; Cells, Cultured; Drug Discovery; Genotype; Heart Diseases; Humans; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Phenotype; Toxicity Tests

Cardiovascular disease remains the largest single cause of mortality in the Western world, despite significant advances in clinical management over the years. Unfortunately, the development of new cardiovascular medicines is stagnating and can in part be attributed to the difficulty of screening for novel therapeutic strategies due to a lack of suitable models. The advent of human induced pluripotent stem cells and the ability to make limitless numbers of cardiomyocytes could revolutionize heart disease modeling and drug discovery. This review summarizes the state of the art in the field, describes the strengths and weaknesses of the technology, and applications where the model system would be most appropriate.

Topics: Animals; Cardiovascular Agents; Drug Discovery; Heart Diseases; Humans; Induced Pluripotent Stem Cells; Models, Biological; Myocytes, Cardiac

Topics: Accidents, Traffic; Age Factors; Aged; Aged, 80 and over; Automobile Driving; Cardiovascular Agents; Geriatric Assessment; Heart Diseases; Humans; Risk Assessment; Risk Factors; Safety

Chymase is primarily found in mast cells (MCs), fibroblasts, and vascular endothelial cells. MC chymase is released into the extracellular interstitium in response to inflammatory signals, tissue injury, and cellular stress. Among many functions, chymase is a major extravascular source for angiotensin II (Ang II) generation. Several recent pre-clinical and a few clinical studies point to the relatively unrecognized fact that chymase inhibition may have significant therapeutic advantages over other treatments in halting progression of cardiac and vascular disease.. The present review covers patent literature on chymase inhibitors for the treatment of cardiac diseases registered between 2010 and 2018.. Increase in cardiac MC number in various cardiac diseases has been found in pathological tissues of human and experimental animals. Meta-analysis data from large clinical trials employing angiotensin-converting enzyme (ACE) inhibitors show a relatively small risk reduction of clinical cardiovascular endpoints. The disconnect between the expected benefit associated with Ang II blockade of synthesis or activity underscores a greater participation of chymase compared to ACE in forming Ang II in humans. Emerging literature and a reconsideration of previous studies provide lucid arguments to reconsider chymase as a primary Ang II forming enzyme in human heart and vasculature.

Topics: Animals; Cardiovascular Agents; Chymases; Drug Design; Enzyme Inhibitors; Heart Diseases; Humans; Mast Cells; Patents as Topic

Twenty years after the initial description of a tissue engineered construct, 3-dimensional human cardiac tissues of different kinds are now generated routinely in many laboratories. Advances in stem cell biology and engineering allow for the generation of constructs that come close to recapitulating the complex structure of heart muscle and might, therefore, be amenable to industrial (eg, drug screening) and clinical (eg, cardiac repair) applications. Whether the more physiological structure of 3-dimensional constructs provides a relevant advantage over standard 2-dimensional cell culture has yet to be shown in head-to-head-comparisons. The present article gives an overview on current strategies of cardiac tissue engineering with a focus on different hydrogel methods and discusses perspectives and challenges for necessary steps toward the real-life application of cardiac tissue engineering for disease modeling, drug development, and cardiac repair.

Topics: Animals; Cardiology; Cardiovascular Agents; Cell Culture Techniques; Cells, Cultured; Disease Models, Animal; Drug Discovery; Drug Evaluation, Preclinical; Heart Diseases; Humans; Myocardium; Myocytes, Cardiac; Phenotype; Recovery of Function; Regeneration; Regenerative Medicine; Stem Cell Transplantation; Tissue Engineering; Tissue Scaffolds

The increasing rate of cardiovascular diseases, the improved survival after the acute phase, the aging of the population and the implementation of primary prevention caused an exponential increase in outpatient cardiac performance, thereby making it difficult to maintain a balance between the citizen-patient request and the economic sustainability of the healthcare system. On the other side, the prescription of many diagnostic tests with a view to defensive medicine and the related growth of patients' expectations, has led several scientific societies to educational campaigns highlighting the concept that "less is more".The present document is aimed at providing the general practitioner with practical information about a prompt diagnosis of signs/symptoms (angina, dyspnea, palpitations, syncope) of the major cardiovascular diseases. It will also provide an overview about appropriate use of diagnostic exams (echocardiogram, stress test), about the appropriate timing of their execution, in order to ensure effectiveness, efficiency, and equity of the health system.

Topics: Algorithms; Ambulatory Care; Cardiovascular Agents; Clinical Decision-Making; Diagnostic Techniques, Cardiovascular; Disease Management; Dyspnea; Follow-Up Studies; Health Priorities; Heart Diseases; Humans; Hypertension; Outpatients; Practice Guidelines as Topic; Symptom Assessment; Time Factors

The ability to generate patient/disease-specific human pluripotent stem cell (hPSC)-derived cardiomyocytes (hPSC-CMs) brings a unique value to the fields of cardiac disease modeling, drug testing, drug discovery, and precision medicine. Further integration of emerging innovative technologies such as developmental-biology inspired differentiation into chamber-specific cardiomyocyte subtypes, genome-editing, tissue-engineering, and novel functional phenotyping methodologies should facilitate even more advanced investigations. Here, we review cornerstone concepts and recent highlights of hPSC-based cardiac disease modeling and drug testing.

Topics: Animals; Cardiovascular Agents; Drug Discovery; Drug Evaluation, Preclinical; Heart Diseases; Humans; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Pluripotent Stem Cells

Kidney transplants are the most common solid organ abdominal transplant and are occasionally performed simultaneously with pancreas transplants in diabetic patients. Preoperative evaluation of potential transplant recipients should focus on the potential for occult cardiovascular disease while also screening for other signs of end-organ dysfunction. Intraoperatively, it is of utmost importance to ensure adequate graft perfusion to limit the risk of postoperative graft dysfunction or rejection. Postoperative care of the kidney or pancreas transplant patient should focus on ensuring normalization of volume status, electrolyte concentrations, and glycemic control.

Topics: Anesthesia; Cardiovascular Agents; Diabetes Mellitus; Fluid Therapy; Heart Diseases; Humans; Kidney Transplantation; Pancreas Transplantation; Postoperative Complications; Renal Dialysis; Renal Insufficiency

Calcium (Ca

Topics: Animals; Calcium Signaling; Cardiovascular Agents; Cell Nucleus; Cytosol; Excitation Contraction Coupling; Gene Expression Regulation; Heart Diseases; Humans; Kinetics; Myocardial Contraction; Myocytes, Cardiac; Transcription, Genetic

Colchicine has been suggested to be beneficial in preventing recurrent pericarditis. The goal of this study was to review all randomized controlled trials that assess the use of colchicine for the prevention and treatment of cardiac diseases.. We performed a meta-analysis of the effects of colchicine on pericarditis, postpericardiotomy syndrome and postprocedural atrial fibrillation recurrence, in-stent restenosis, gastrointestinal adverse effects, and treatment discontinuation rates. We conducted an EMBASE and MEDLINE search for prospective controlled trials.. We identified 17 prospective controlled randomized studies with 2082 patients that received colchicine and 1982 controls with an average follow-up duration of 12 months. Treatment with colchicine is associated with reduced risk of pericarditis recurrence/postpericardiotomy syndrome (OR: 0.37; 95% CI: 0.29-0.47; P<0.001) and lower recurrence of atrial fibrillation rates after cardiac surgery and ablation procedures. However, gastrointestinal side effects were more common in patients treated with colchicine (OR: 2.6; 95% CI: 1.82-3.72; P<0.001) in all subgroups except for those treated for prevention of recurrent pericarditis. The higher rates of side effects resulted in higher incidence of treatment discontinuation in patients treated with colchicine.. Colchicine appears to be efficacious and well tolerated for recurrent pericarditis/postpericardiotomy syndrome and recurrence of postprocedural atrial fibrillation. However, its efficacy may be limited by its gastrointestinal adverse events and treatment discontinuation rates particularly in postoperative patients.

Topics: Aged; Cardiovascular Agents; Chi-Square Distribution; Colchicine; Gastrointestinal Diseases; Heart Diseases; Humans; Middle Aged; Odds Ratio; Risk Factors; Treatment Outcome

Topics: Cardiovascular Agents; Drug Administration Schedule; Heart Diseases; Humans; Medication Adherence; Mortality; Postoperative Care; Postoperative Complications; Treatment Outcome

Cardiac practice involves the application of a range of pharmacological therapies. An anesthesiologist needs to keep pace with the rampant drug developments in the field of cardiovascular medicine for appropriate management in both perioperative and intensive care set-up, to strengthen his/her role as a perioperative physician in practice. The article reviews the changing trends and the future perspectives in major classes of cardiovascular medicine.

Topics: Cardiovascular Agents; Critical Care; Heart Diseases; Humans; Perioperative Care

Anthracycline chemotherapy maintains a prominent role in treating many forms of cancer. Cardiotoxic side effects limit their dosing and improved cancer outcomes expose the cancer survivor to increased cardiovascular morbidity and mortality. The basic mechanisms of cardiotoxicity may involve direct pathways for reactive oxygen species generation and topoisomerase 2 as well as other indirect pathways. Cardioprotective treatments are few and those that have been examined include renin angiotensin system blockade, beta blockers, or the iron chelator dexrazoxane. New treatments exploiting the ErbB or other novel pro-survival pathways, such as conditioning, are on the cardioprotection horizon. Even in the forthcoming era of targeted cancer therapies, the substantial proportion of today's anthracycline-treated cancer patients may become tomorrow's cardiac patient.

Topics: Animals; Anthracyclines; Antibiotics, Antineoplastic; Cardiotoxicity; Cardiovascular Agents; Cytoprotection; Heart Diseases; Humans; Myocytes, Cardiac; Risk Factors; Signal Transduction; Time Factors; Troponin

Phosphodiesterase 5 inhibitors (PDE5i) were developed while investigating novel treatments for coronary artery disease, but their andrological side effects shifted their indication toward the management of erectile dysfunction. Although PDE5i are now also indicated for pulmonary arterial hypertension and there are mounting preclinical and clinical evidences about their potentially beneficial cardiac effects, their use remains controversial and the involved mechanisms remain unclear.. This review aimed to analyze the effects of PDE5i administration in various animal and humans models of cardiovascular diseases.. Animal studies have shown that PDE5i have protective effects in several models of cardiac disease. In humans, some studies showed that PDE5i improves microvascular and endothelial dysfunction and exerts positive effects in different samples of cardiovascular (CV) impairment. In contrast, other studies found no benefit (and no harm) in heart failure with preserved ejection fraction. The discrepancies in these findings are likely related to the fact that the mechanisms targeted by PDE5i in human disease are still poorly understood and the target population not yet identified. The mechanisms of actions herein reviewed suggest that hypertrophy, microvascular impairment, and inflammation, should be variably present for PDE5i to work. All these conditions frequently coexist in diabetes. A gender responsiveness has also been recently proposed.. Continuous PDE5 inhibition may exert cardioprotective effects, improving endothelial function and counteracting cardiac remodeling in some but not all conditions. A better patient selection could help to clarify the controversies on PDE5i use for CV disorders.

Topics: Animals; Cardiotonic Agents; Cardiovascular Agents; Cardiovascular Diseases; Endothelium, Vascular; Heart; Heart Diseases; Humans; Microvessels; Myocardium; Phosphodiesterase 5 Inhibitors; Reproducibility of Results

Topics: Cardiovascular Agents; Drug-Related Side Effects and Adverse Reactions; Female; Heart Diseases; Humans; Hypertension; Male; Needs Assessment; Sex Factors; Treatment Outcome

Human heart failure due to myocardial infarction is a major health concern. The paucity of organs for transplantation limits curative approaches for the diseased and failing adult heart. Human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs) have the potential to provide a long-term, viable, regenerative-medicine alternative. Significant progress has been made with regard to efficient cardiac myocyte generation from hiPSCs. However, directing hiPSC-CMs to acquire the physiological structure, gene expression profile and function akin to mature cardiac tissue remains a major obstacle. Thus, hiPSC-CMs have several hurdles to overcome before they find their way into translational medicine. In this review, we address the progress that has been made, the void in knowledge and the challenges that remain. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

Topics: Calcium Signaling; Cardiovascular Agents; Cell Differentiation; Cell Lineage; Cells, Cultured; Drug Discovery; Gene Expression Regulation, Developmental; Genetic Markers; Genotype; Heart Diseases; Humans; Induced Pluripotent Stem Cells; Mutation; Myocardial Contraction; Myocytes, Cardiac; Phenotype; Recovery of Function; Regeneration; Regenerative Medicine; Sarcomeres; Stem Cell Transplantation; Tissue Engineering

Peroxisome proliferator-activated receptors, PPARα, PPARβ/δ, and PPARγ, are a group of nuclear receptors that function as transcriptional regulators of lipid metabolism, energy homeostasis, and inflammation. Given the role of metabolism imbalance under pathological states of the heart, PPARs have emerged as important therapeutic targets, and accumulating evidence highlights their protective role in the improvement of cardiac function under diverse pathological settings. Although the role of PPARs in the regulation of cardiac substrate utilization preference and energy homeostasis is well documented, their effects related to the regulation of cellular inflammatory and redox responses in the heart are less studied. In this review, we provide an overview on recent progress with respect to understanding the role of the nonmetabolic effects of PPARs in cardiac dysfunction, namely during ischemia/reperfusion injury, hypertrophy, and cardiac failure, and highlight the mechanisms underlying the protective effects against inflammation, oxidative stress, and cell death. The role of receptor-independent, nongenomic effects of PPAR agonists is also discussed.

Topics: Animals; Cardiovascular Agents; Drug Design; Heart Diseases; Humans; Molecular Targeted Therapy; Myocardium; Peroxisome Proliferator-Activated Receptors; Signal Transduction

This review discusses historical milestones, recent developments and challenges in the area of 3D culture models with cardiovascular cell types. Expectations in this area have been raised in recent years, but more relevant in vitro research, more accurate drug testing results, reliable disease models and insights leading to bioartificial organs are expected from the transition to 3D cell culture. However, the construction of organ-like cardiac 3D models currently remains a difficult challenge. The heart consists of highly differentiated cells in an intricate arrangement.Furthermore, electrical “wiring”, a vascular system and multiple cell types act in concert to respond to the rapidly changing demands of the body. Although cardiovascular 3D culture models have been predominantly developed for regenerative medicine in the past, their use in drug screening and for disease models has become more popular recently. Many sophisticated 3D culture models are currently being developed in this dynamic area of life science. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

Topics: Animals; Cardiovascular Agents; Cell Communication; Cell Culture Techniques; Cell Differentiation; Cells, Cultured; Coculture Techniques; Diffusion of Innovation; Drug Discovery; Heart Diseases; Humans; Myocytes, Cardiac; Phenotype; Regenerative Medicine; Tissue Engineering

In the heart, Ca(2+) signals regulate a variety of biological functions ranging from contractility to gene expression, cellular hypertrophy and death. In this review, we summarize the role of local Ca(2+) homeostasis in these processes in healthy cardiac muscle cells, and highlight how mismanaged Ca(2+) handling contributes to the pathophysiology of conditions such as cardiac arrhythmia, ischemic heart disease, cardiac hypertrophy and heart failure. Aiming to provide an introduction to the field with a clinical perspective, we also indicate how current and future therapies may modulate cardiomyocytes Ca(2+) handling for the treatment of patients.

Topics: Action Potentials; Animals; Calcium; Calcium Signaling; Cardiovascular Agents; Excitation Contraction Coupling; Heart Diseases; Humans; Kinetics; Myocardial Contraction; Myocytes, Cardiac

Cardiac drug discovery is hampered by the reliance on non-human animal and cellular models with inadequate throughput and physiological fidelity to accurately identify new targets and test novel therapeutic strategies. Similarly, adverse drug effects on the heart are challenging to model, contributing to costly failure of drugs during development and even after market launch. Human induced pluripotent stem cell derived cardiac tissue represents a potentially powerful means to model aspects of heart physiology relevant to disease and adverse drug effects, providing both the human context and throughput needed to improve the efficiency of drug development. Here we review emerging technologies for high throughput measurements of cardiomyocyte physiology, and comment on the promises and challenges of using iPSC-derived cardiomyocytes to model disease and introduce the human context into early stages of drug discovery. This article is part of a Special Issue entitled: Cardiomyocyte biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

Topics: Animals; Cardiovascular Agents; Cell Differentiation; Cell Lineage; Cell Proliferation; Cells, Cultured; Drug Discovery; Genetic Predisposition to Disease; Heart Diseases; High-Throughput Screening Assays; Humans; Induced Pluripotent Stem Cells; Myocardial Contraction; Myocytes, Cardiac; Phenotype; Risk Assessment

The second messenger cyclic guanosine 3'5' monophosphate (cGMP) and its downstream effector protein kinase G (PKG) have been discovered more than 40 years ago. In vessels, PKG1 induces smooth muscle relaxation in response to nitric oxide signalling and thus lowers systemic and pulmonary blood pressure. In platelets, PKG1 stimulation by cGMP inhibits activation and aggregation, and in experimental models of heart failure (HF), PKG1 activation by inhibiting cGMP degradation is protective. The net effect of the above-mentioned signalling is cardiovascular protection. Yet, while modulation of cGMP-PKG has entered clinical practice for treating pulmonary hypertension or erectile dysfunction, translation of promising studies in experimental HF to clinical success has failed thus far. With the advent of new technologies, novel mechanisms of PKG regulation, including mechanosensing, redox regulation, protein quality control, and cGMP degradation, have been discovered. These novel, non-canonical roles of PKG1 may help understand why clinical translation has disappointed thus far. Addressing them appears to be a requisite for future, successful translation of experimental studies to the clinical arena.

Topics: Animals; Cardiovascular Agents; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Heart Diseases; Humans; Molecular Targeted Therapy; Myocardium; Oxidation-Reduction; Phosphodiesterase 5 Inhibitors; Proteasome Endopeptidase Complex; Protein Kinase Inhibitors; Signal Transduction; Stress, Physiological; TRPC Cation Channels

Recurrent ventricular arrhythmias (VA) are a source of significant morbidity in patients without structural heart disease (SHD) and also mortality in patients with SHD. The treatment goals for these two patient populations differ greatly. Areas covered: The secondary prevention of recurrent VA in patients without and with SHD will be reviewed, focusing on clinical data (especially randomized, controlled trials) in the literature as determined through searches in PubMed and ClinicalTrials.gov. This will include β blockers, non-dihydropyridine calcium channel blockers and antiarrhythmic drugs in both subgroups and non-antiarrhythmic medications in SHD. Expert commentary: The available options for medical therapy for VA in both normal hearts and SHD are insufficient, due to substandard efficacy and toxicities. While non-pharmacologic therapies may provide an excellent option, further drug development and randomized trials are needed, as is a reappraisal of the current mode of utilization.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium Channel Blockers; Cardiovascular Agents; Catheter Ablation; Heart Diseases; Humans; Randomized Controlled Trials as Topic; Recurrence; Tachycardia, Ventricular; Ventricular Fibrillation; Ventricular Premature Complexes

Cardiac glycosides, the cardiotonic steroids such as digitalis have been in use as heart ailment remedy since ages. They manipulate the renin-angiotensin axis to improve cardiac output. However; their safety and efficacy have come under scrutiny in recent times, as poisoning and accidental mortalities have been observed. In order to better understand and exploit them as cardiac ionotropes, studies are being pursued using different cardiac glycosides such as digitoxin, digoxin, ouabain, oleandrin etc. Several cardiac glycosides as peruvoside have shown promise in cancer control, especially ovary cancer and leukemia. Functional variability of these glycosides has revealed that not all cardiac glycosides are alike. Apart from their specific affinity to sodium-potassium ATPase, their therapeutic dosage and behavior in poly-morbidity conditions needs to be considered. This review presents a concise account of the key findings in recent years with adequate elaboration of the mechanisms. This compilation is expected to contribute towards management of cardiac, cancer, even viral ailments.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cardenolides; Cardiac Glycosides; Cardiovascular Agents; Enzyme Inhibitors; Heart Diseases; Humans; Neoplasms; Renin-Angiotensin System; Saponins; Sodium-Potassium-Exchanging ATPase

Acetylsalicylic acid (aspirin) is a prototypic cyclooxygenase (COX) inhibitor. It was synthesized serendipitously from a natural compound, i.e., salicylic acid, with known analgesic activity. This chemical modification, obtained for the first time in an industrial environment in 1897, endowed aspirin with the unique capacity of acetylating and inactivating permanently COX-isozymes. Traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) were developed to mimic the pharmacological effects of aspirin, using aspirin-sensitive experimental models of pain and inflammation as the template for screening new chemical entities. Among the tNSAIDs, some were endowed with moderate COX- selectivity (e.g., diclofenac), but no studies of sufficient size and duration were performed to show any clinically relevant difference between different members of the class. Similarly, no serious attempts were made to unravel the mechanisms involved in the shared therapeutic and toxic effects of tNSAIDs until the discovery of COX-2. This led to characterizing their main therapeutic effects as being COX-2-dependent and their gastrointestinal (GI) toxicity as being COX-1-dependent, and provided a rationale for developing a new class of selective COX-2 inhibitors, the coxibs. This review will discuss the clinical pharmacology of tNSAIDs and coxibs, and the clinical read-outs of COX-isozyme inhibition. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance."

Topics: Animals; Anticarcinogenic Agents; Cardiovascular Agents; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Gastrointestinal Diseases; Heart Diseases; Humans; Inflammation; Isoenzymes; Molecular Structure; Neoplasms; Risk Factors; Signal Transduction; Structure-Activity Relationship

One target of toxicity caused by cardiac drugs is the mitochondrion. This review focuses on the mitochondrion-toxic effects of cardiac drugs and the extent to which mitochondrion-mediated side effects influence the treatment of cardiac disease in mitochondrial disorders (MIDs).. Areas discussed in this review include the pathogenesis of mitochondrion toxicity and the mechanisms by which cardiac drugs exhibit their mitochondrion-toxic effect. Whenever available, the mitochondrion-toxic effect of cardiac drugs in patients with a MID is highlighted.. Most of the drugs used in cardiology are somewhat mitochondrion-toxic. The degree of toxicity, however, is variable and dependent on the type of drug, tissue, organ, subject, cell system investigated, the co-medication, and the conditions under which the investigations have been carried out. Abnormalities induced by mitochondrion-toxic cardiac drugs include impairment of respiratory chain functions resulting in reduced ATP production, increased production of reactive oxygen species with increased oxidation of proteins or lipids, reduction of the mitochondrial membrane potential and apoptosis. Several other mitochondrial functions may be additionally impaired by culprit compounds. Cardiac drugs that should be applied with particular caution in patients with MIDs include amiodarone, phenytoin, lidocaine, quinidine, isoproterenol, clopidogrel, acetyl-salicylic acid and molsidomine.

Topics: Animals; Cardiovascular Agents; Heart Diseases; Humans; Mitochondria; Mitochondrial Diseases; Reactive Oxygen Species

Suboptimal intrauterine development has been linked to predisposition to cardiovascular disease in adulthood, a concept termed 'developmental origins of health and disease'. Although the exact mechanisms underlying this developmental programming are unknown, a growing body of evidence supports the involvement of epigenetic regulation. Epigenetic mechanisms such as DNA methylation, histone modifications and micro-RNA confer added levels of gene regulation without altering DNA sequences. These modifications are relatively stable signals, offering possible insight into the mechanisms underlying developmental origins of health and disease. This review will discuss the role of epigenetic mechanisms in heart development as well as aberrant epigenetic regulation contributing to cardiovascular disease. Additionally, we will address recent advances targeting epigenetic mechanisms as potential therapeutic approaches to cardiovascular disease.

Topics: Animals; Cardiovascular Agents; Chromatin Assembly and Disassembly; DNA Methylation; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Genetic Markers; Genetic Predisposition to Disease; Genetic Therapy; Heart; Heart Diseases; Humans; MicroRNAs; Morphogenesis; Phenotype

The current review will address key topics and recommendations of the recent 2014 update of the American College of Cardiology and American Heart Association clinical practice guideline for the perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery.. The completely rewritten guideline provides a stepwise approach for the identification and management of patients at highest risk for major adverse cardiac events and discusses new or updated recommendations. For example, β-blockers should be continued perioperatively but treatment should not be initiated within 24 h of noncardiac surgery. Angiotensin-converting enzyme inhibitors should be continued, but if held, may be restarted as soon as feasible. Routine aspirin therapy is not recommended without previous coronary stent implantation or risk assessment for myocardial ischemia. Elective noncardiac surgery should not be performed within 30 days of bare metal stent or 12 months of drug-eluting stent implantation because of in-stent thrombosis as well as bleeding risk from dual antiplatelet therapy during surgery. Noncardiac surgery may be considered, however, in patients on antiplatelet agents 180 days after drug-eluting stent placement if risk of surgical delay exceeds risk of stent thrombosis from cessation of antiplatelet therapy.. In conclusion, this review will discuss the important topics from the 2014 American College of Cardiology/American Heart Association guideline in order to provide the perioperative physician with the most recent evidence necessary to minimize major adverse cardiac events in patients undergoing noncardiac surgery.

Topics: Algorithms; Cardiovascular Agents; Elective Surgical Procedures; Heart Diseases; Humans; Perioperative Care; Surgical Procedures, Operative

Ventricular arrhythmia is the leading cause of sudden cardiac death (SCD). Deranged cardiac metabolism and abnormal redox state during cardiac diseases foment arrhythmogenic substrates through direct or indirect modulation of cardiac ion channel/transporter function. This review presents current evidence on the mechanisms linking metabolic derangement and excessive oxidative stress to ion channel/transporter dysfunction that predisposes to ventricular arrhythmias and SCD. Because conventional antiarrhythmic agents aiming at ion channels have proven challenging to use, targeting arrhythmogenic metabolic changes and redox imbalance may provide novel therapeutics to treat or prevent life-threatening arrhythmias and SCD.

Topics: Arrhythmias, Cardiac; Calcium Signaling; Cardiovascular Agents; Death, Sudden, Cardiac; Gap Junctions; Heart Conduction System; Heart Diseases; Homeostasis; Humans; Ion Channel Gating; Ion Channels; Membrane Potentials; Metabolic Diseases; Mitochondria, Heart; Myocardium; Oxidation-Reduction; Oxidative Stress; Potassium; Reactive Oxygen Species; Sodium

Sudden cardiac death is a common cause of death in patients with structural heart disease, genetic mutations, or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with sudden cardiac death. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology, including ion channel expression. Most commonly used cellular models are cellular transfection models, which are able to mimic the expression of a single-ion channel offering incomplete insight into changes of the action potential profile. Induced pluripotent stem cell-derived cardiomyocytes resemble, but are not identical, adult human cardiomyocytes and provide a new platform for studying arrhythmic disorders leading to sudden cardiac death. A variety of platforms exist to phenotype cellular models, including conventional and automated patch clamp, multielectrode array, and computational modeling. Induced pluripotent stem cell-derived cardiomyocytes have been used to study long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, and other hereditary cardiac disorders. Although induced pluripotent stem cell-derived cardiomyocytes are distinct from adult cardiomyocytes, they provide a robust platform to advance the science and clinical care of sudden cardiac death.

Topics: Animals; Cardiovascular Agents; Cell Differentiation; Cells, Cultured; Clinical Trials as Topic; Computer Simulation; Death, Sudden, Cardiac; Disease Models, Animal; Drug Evaluation, Preclinical; Electrophysiology; Forecasting; Heart Diseases; Humans; Induced Pluripotent Stem Cells; Ion Channels; Long QT Syndrome; Models, Cardiovascular; Myocytes, Cardiac; Organ Culture Techniques; Patch-Clamp Techniques; Tachycardia, Ventricular

Dietary supplements may have adverse effects and potentially interact with conventional medications. They are perceived as "natural" products, free of side effects with no need for medical consultation. Little is known about consumption of dietary supplements by patients with cardiac diseases. The objective of this study was to investigate dietary supplement consumption among cardiac patients admitted to internal and cardiology wards. Potential drug-dietary supplement interactions were also assessed.. During a period of 6 months, patients with cardiac disease hospitalized in the Internal Medicine and Cardiology Wards at Assaf Harofeh Medical Center were evaluated regarding their dietary supplement consumption. A literature survey examining possible drug-supplement interaction was performed.. Out of 149 cardiac patients, 45% were dietary supplement consumers. Patients ad-mitted to the Internal Medicine Wards consumed more dietary supplements than those admit-ted to the Cardiology Division. Dietary supplement consumption was associated with older age (OR = 1.05, p = 0.022), female gender (OR = 2.94, p = 0.014) and routine physical activity (OR = 3.15, p = 0.007). Diabetes mellitus (OR = 2.68, p = 0.020), hematological diseases (OR = 13.29, p = 0.022), and the use of anti-diabetic medications (OR = 4.28, p = 0.001) were independently associated with dietary supplement intake. Sixteen potential moderate interactions between prescribed medications and dietary supplements were found.. Consumption of dietary supplements is common among cardiac patients. It is more common in those admitted to Internal Medicine Departments than in those admitted to the Cardiology Wards. Due to the risk of various drug-supplement interactions consumed by patients with cardiac diseases, there is a need to increase awareness and knowledge among medical staff regarding the intake of dietary supplements.

Topics: Academic Medical Centers; Aged; Cardiology Service, Hospital; Cardiovascular Agents; Chi-Square Distribution; Dietary Supplements; Drug Interactions; Female; Heart Diseases; Humans; Internal Medicine; Israel; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Patient Admission; Risk Assessment; Risk Factors; Surveys and Questionnaires

The health of the cardiovascular and pulmonary systems is inextricably linked to the renin-angiotensin system (RAS). Physiologically speaking, a balance between the vasodeleterious (Angiotensin-converting enzyme [ACE]/Angiotensin II [Ang II]/Ang II type 1 receptor [AT1R]) and vasoprotective (Angiotensin-converting enzyme 2 [ACE2]/Angiotensin-(1-7) [Ang-(1-7)]/Mas receptor [MasR]) components of the RAS is critical for cardiopulmonary homeostasis. Upregulation of the ACE/Ang II/AT1R axis shifts the system toward vasoconstriction, proliferation, hypertrophy, inflammation, and fibrosis, all factors that contribute to the development and progression of cardiopulmonary diseases. Conversely, stimulation of the vasoprotective ACE2/Ang-(1-7)/MasR axis produces a counter-regulatory response that promotes cardiovascular health. Current research is investigating novel strategies to augment actions of the vasoprotective RAS components, particularly ACE2, in order to treat various pathologies. Although multiple approaches to increase the activity of ACE2 have displayed beneficial effects against experimental disease models, the mechanisms behind its protective actions remain incompletely understood. Recent work demonstrating a non-catalytic role for ACE2 in amino acid transport in the gut has led us to speculate that the therapeutic effects of ACE2 can be mediated, in part, by its actions on the gastrointestinal tract and/or gut microbiome. This is consistent with emerging data which suggest that dysbiosis of the gut and lung microbiomes is associated with cardiopulmonary disease. This review highlights new developments in the protective actions of ACE2 against cardiopulmonary disorders, discusses innovative approaches to targeting ACE2 for therapy, and explores an evolving role for gut and lung microbiota in cardiopulmonary health.

Topics: Angiotensin-Converting Enzyme 2; Animals; Cardiovascular Agents; Drug Delivery Systems; Heart Diseases; Humans; Lung Diseases; Microbiota; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Proto-Oncogene Mas

Adverse side effects of drugs are a significantly underestimated problem in modern medicine. In this review article, we summarize common adverse side effects of cardiovascular drugs. In particular, we highlight the factors promoting these adverse side effects in patients, including reduced hepatic or renal clearance in elderly patients that often requires dosage adjustment. Pharmacodynamic and pharmacokinetic interactions between drugs (e.g. through the cytochrome P450 system or P-glycoproteins) can modify the plasma concentration of many compounds, thereby also increasing the likelihood of unwanted side effects. The most prominent cardiac side effects include arrhythmias, e.g. atrioventricular (AV) block, drug-induced long-QT syndrome and torsade de pointes and altered inotropy. Non-cardiac side effects are subsequently discussed grouped by drug class. A better understanding of the risks and side effects of cardiovascular drugs is expected to reduce the mortality and morbidity associated with adverse side effects.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Dose-Response Relationship, Drug; Drug Interactions; Heart Diseases; Humans; Risk Assessment

One of actual problems of modern cardiology is assessment and correction of risk of cardiac complications of noncardiac surgery. Recommendations on this issue propose reduction of preoperative examination and wide use of drug therapy, primarily statins and β-blockers. However, new data accumulated in recent years, as well as the recognition of scientific inconsistency of the DECREASE research series, force a new outlook at the problem. In this review in light of new facts the following important issues of perioperative medicine are discussed: administration of β-blockers and statins, volume of preoperative cardiac examination, value of preventive myocardial revascularization.

Topics: Cardiovascular Agents; Heart Diseases; Humans; Myocardial Revascularization; Perioperative Care; Postoperative Complications; Risk Adjustment; Risk Assessment; Surgical Procedures, Operative

Topics: Cardiovascular Agents; Cardiovascular Surgical Procedures; Clinical Trials as Topic; Combined Modality Therapy; Comparative Effectiveness Research; Diagnostic Techniques, Cardiovascular; Heart Diseases; Humans; Outcome and Process Assessment, Health Care; Patient Selection; Therapies, Investigational

Perioperative cardiac complications are a common cause of death and major morbidity in patients undergoing non-cardiac surgery. Preoperative evaluation and medical optimisation can improve outcomes, although the evidence base is limited. Evidence of effectiveness is strongest for prophylactic use of β-blockers in high-risk patients and aspirin in patients with coronary artery disease. Particular challenges arise among patients with heart failure or valvular heart disease or those receiving antithrombotic therapy for coronary artery stents or atrial fibrillation. Close liaison between general practitioners, surgeons, anaesthetists and cardiologists is needed for optimising preoperative management and subsequent clinical outcomes in high-risk patients.

Topics: Cardiovascular Agents; Decision Support Techniques; Elective Surgical Procedures; Health Status Indicators; Heart Diseases; Humans; Percutaneous Coronary Intervention; Postoperative Complications; Preoperative Care; Risk Adjustment; Risk Assessment; Risk Factors

Most chemotherapy regimens in colorectal cancer treatment are 5-fluorouracil (5-FU)/leucovorin or capecitabine-based. Cardiotoxicity is a less common but potentially lethal complication of 5-FU or capecitabine treatment, and some physicians might be unfamiliar with treatment alternatives. Rechallenging should be avoided because it carries a high risk of recurrence of the cardiac symptoms and prophylactic treatment is not always protective. Possible alternative treatment options to be considered are to replace the oral capecitabine or intravenous 5-FU by a 5-FU bolus regimen, by uracil-tegafur or tegafur/gimeracil/oteracil, both oral fluoropyrimidines combining a 5-FU prodrug with a dihydropyrimidine dehydrogenase (DPD) inhibitor, or by raltitrexed, a thymidilate synthase inhibitor whose metabolism is independent of DPD. Patients with advanced colorectal cancer and fluoropyrimidine-induced cardiotoxicity can be treated with other non-fluoropyrimidine related chemotherapy, either as a single agent, combined, or in combination with biological agents. In this report we discuss the different alternative treatment options.

Topics: Animals; Antimetabolites, Antineoplastic; Capecitabine; Cardiovascular Agents; Colorectal Neoplasms; Deoxycytidine; Fluorouracil; Heart Diseases; Humans

The use of medications plays a pivotal role in the management of children with heart diseases. Most children with increased pulmonary blood flow require chronic use of anticongestive heart failure medications until more definitive interventional or surgical procedures are performed. The use of such medications, particularly inotropic agents and diuretics, is even more amplified during the postoperative period. Currently, children are undergoing surgical intervention at an ever younger age with excellent results aided by advanced anesthetic and postoperative care. The most significant of these advanced measures includes invasive and noninvasive monitoring as well as a wide array of pharmacologic agents. This review update provides a medication guide for medical practitioners involved in care of children with heart diseases.

Topics: Cardiology; Cardiovascular Agents; Child; Disease Management; Heart Diseases; Humans; Pediatrics; Pharmacopoeias as Topic

Development of novel cell migration modulators for anti-inflammatory and cardiovascular therapy is a complex task since any modulator will necessarily interfere with a balanced system of physiological regulators directing proper positioning of diverse immune cell types within the body. Whereas this shall serve efficient pathogen elimination, lack of proper control over these processes may result in counterproductive chronic inflammation and progressive tissue injury instead of healing. Prediction of the therapeutic potential or side effects of any migration modulator is not possible based on theoretical considerations alone but needs to be experimentally evaluated in preclinical disease models and by clinical studies. Here, we briefly summarize basic mechanism of cell migration, and groups of synthetic drugs currently in use for migration modulation. We then discuss one fundamental problem encountered with single-target approaches that arises from the complexity of any inflammation, with multiple interacting and often redundant factors being involved. This issue is likely to arise for any class of therapeutic agent (small molecules, peptides, antibodies, regulatory RNAs) addressing a single gene or protein. Against this background of studies on synthetic migration modulators addressing single targets, we then discuss the potential of endogenous proteins as therapeutic migration modulators, or as parent compounds for the development of mimetic drugs. Regulatory proteins of this type commonly address multiple receptors and signalling pathways and act upon the immune response in a phase-specific manner. Based on recent evidence, we suggest investigation of such endogenous migration modulators as novel starting points for anti-inflammatory and cardiovascular drug development.

Topics: Animals; Anti-Inflammatory Agents; Cardiovascular Agents; Cell Movement; Drug Delivery Systems; Drug Discovery; Heart Diseases; Humans; Immune System; MicroRNAs; Models, Biological

Ranolazine which is currently approved as an antianginal agent reduces the Na-dependent Ca overload via inhibition of the late sodium current (late I(Na)) and thus improves diastolic tone and oxygen handling during myocardial ischemia. According to accumulating evidence ranolazine also exerts beneficial effects on diastolic and systolic heart failure where late I(Na) was also found to be elevated. Moreover, late I(Na) plays a crucial role as an arrhythmic substrate. Ranolazine has been described to have antiarrhythmic effects on ventricular as well as atrial arrhythmias without any proarrythmia or severe organ toxicity as it is common for several antiarrhythmic drugs. In patients with diabetes, treatment with ranolazine led to a significant improvement of glycemic control. In this article possible new clinical indications of the late I(Na)-inhibitor ranolazine are reviewed. We summarize novel experimental and clinical studies and discuss the significance of the available data.

Topics: Acetanilides; Animals; Cardiovascular Agents; Diabetes Mellitus; Heart Diseases; Humans; Piperazines; Ranolazine

This article provides cardiologists with a broad overview of recent advances in clinical cardiology that could affect their daily practice in the near future. It discusses new ways of interacting with primary care physicians, the most recent findings on the remote monitoring of chronic disease, and the latest publications on the drugs used in routine clinical practice. The article ends with a summary of the work carried out by the Clinical Cardiology Section of the Spanish Society of Cardiology during the last year.

Topics: Anticoagulants; Cardiology; Cardiovascular Agents; Chronic Disease; Heart Diseases; Heart Valve Diseases; Humans; Platelet Aggregation Inhibitors; Primary Health Care

The morbidity and mortality associated with vascular surgery procedures are largely the results of cardiac events. National guidelines have been regularly proposed and updated by the American College of Cardiology (ACC)/American Heart Association (AHA) to ensure optimal perioperative management and risk stratification. Controversy remains between experts and other cardiology societies regarding several patient care issues including revascularization before surgery, timing of β-blocker therapy, and the administration of antiplatelet therapy. Several landmark articles recently published have helped to modify the guidelines in the hope of improving vascular patient outcomes. In this review, we searched all recent available literature pertaining to perioperative cardiac evaluation before major vascular surgery. We propose an algorithm for preoperative cardiac evaluation, which is a modification to the AHA recommendations. Incorporated in this algorithm are recent published pivotal articles that can help in guiding physicians caring for the vascular patient requiring major operative or endovascular interventions.

Topics: Algorithms; Anesthesia; Cardiac Surgical Procedures; Cardiovascular Agents; Endovascular Procedures; Heart Diseases; Heart Function Tests; Humans; Practice Guidelines as Topic; Predictive Value of Tests; Preoperative Care; Risk Assessment; Risk Factors; Treatment Outcome; Vascular Diseases; Vascular Surgical Procedures

Naturally occurring plant alkaloids, in particular those identified from herbal medicines, are finding therapeutic use. Heart diseases can be well managed with specific formulations of herbal medicines. The combined action of multiple constituents of herbal medicines works with therapeutic benefits in humans. The established formulations of Traditional Chinese medicines show efficacy in treatment of diseases. However, individual herbal principles seldom show pharmacological activity. Nevertheless, some of the active alkaloids and terpenoids from medicinal herbs have been identified. The pharmacological activities of these herbal compounds have been studied. These active constituents of herbal medicine are also used in nutrient supplements, but the modes of action of the active component remain sketchy. The present review describes the recent development of those active principles from herbal medicines as cardiovascular agents. The study will provide insights into herbal medicines for drug development for the treatment of cardiovascular disease.

Topics: Cardiovascular Agents; Heart Diseases; Humans; Medicine, Chinese Traditional; Phytotherapy; Plants, Medicinal

Autophagy is an evolutionarily conserved intracellular mechanism for degradation of long-lived proteins and organelles. Accumulating lines of evidence indicate that autophagy is deeply involved in the development of cardiac disease. Autophagy is upregulated in almost all cardiac pathological states, exerting both protective and detrimental functions. Whether autophagy activation is an adaptive or maladaptive mechanism during cardiac stress seems to depend upon the pathological context in which it is upregulated, the extent of its activation, and the signaling mechanisms promoting its enhancement. Pharmacological modulation of autophagy may therefore represent a potential therapeutic strategy to limit myocardial damage during cardiac stress. Several pharmacological agents that are able to modulate autophagy have been identified, such as mammalian target of rapamycin inhibitors, adenosine monophosphate-dependent kinase modulators, sirtuin activators, myo-inositol-1,4,5-triphosphate and calcium-lowering agents, and lysosome inhibitors. Although few of these modulators of autophagy have been directly tested during cardiac stress, many of them seem to have high potential to be efficient in the treatment of cardiac disease. We will discuss the potential usefulness of different pharmacological activators and inhibitors of autophagy in the treatment of cardiac diseases.

Topics: Animals; Autophagy; Cardiovascular Agents; Enzyme Inhibitors; Heart Diseases; Humans; Inositol 1,4,5-Trisphosphate; Stress, Physiological; TOR Serine-Threonine Kinases

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

Discoveries of the cardiac natriuretic peptides ANP, BNP, and CNP along with studies of their function and regulation in health and disease, have led to breakthroughs in the understanding and clinical management of heart failure. Analysis of the ANP and BNP promoters and patterns of expression uncovered a set of key regulators and pathways that converge onto these sensitive markers of early myocyte differentiation and cardiac stress. Among the most studied are the transcription factors GATA4, TBX5, and NKX2-5, which are central to cardiac development and mutations of which are associated with congenital heart disease. In clinical practice, plasma natriuretic peptides levels have been used as quantitative biomarkers of heart failure and proved to be highly effective for the diagnosis of heart failure, for risk-stratification of patients and guided therapy, as well as for screening for subclinical cardiac stress. Emerging studies are revealing the cardioprotective attributes of these peptides and may offer new therapeutic venues for myocardial infarction and heart failure. Clinical trials have documented the benefits and risks of the use of synthetic ANP (Anaritide) and BNP (Nesiritide) for treating heart failure, renal failure, and hypertension. This review summarizes the function and regulation of cardiac natriuretic peptides and the translation of the basic biochemical discoveries into clinical practice both at the diagnostic and therapeutic level.

Topics: Amino Acid Sequence; Animals; Biomarkers; Cardiovascular Agents; Gene Expression Regulation; Heart Diseases; Humans; Molecular Sequence Data; Myocardium; Natriuretic Peptides; Predictive Value of Tests; Prognosis; Transcription Factors

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

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

There is increasing recognition that coronary microvascular dysfunction also plays an important role in coronary heart disease. Little is known about this aspect of coronary heart disease due to difficulties in studying the coronary microcirculation directly. The retina is a unique site where the microcirculation can be imaged directly, providing an opportunity to study in vivo the structure and pathology of the human circulation and the possibility of detecting changes in microvasculature relating to the development of cardiovascular disease. This review covers the recent progress in research linking retinal vascular signs to coronary heart disease, and finds accumulating evidence that retinal vascular signs may provide a window into the health of the coronary microvasculature. The most widely studied signs, arteriolar narrowing, and more recently, venular dilation, are likely associated with increased risk of coronary heart disease in women, independent of traditional risk factors. Attempts to improve coronary heart disease risk prediction by incorporating retinal vessel calibre size into risk prediction scores complementing traditional algorithms such as the Framingham risk scores have so far been disappointing. Research is ongoing into the predictive utility of other retinal vascular signs. Retinal photography provides long-lasting records that enable monitoring of longitudinal changes in these retinal signs and vascular health. Full English text available fromwww.revespcardiol.org.

Topics: Cardiovascular Agents; Coronary Disease; Heart Diseases; Humans; Microcirculation; Retinal Vessels; Risk Factors

Apoptosis or progress of programmed cell death is a tightly regulated process which plays an important role in various cardiovascular diseases particularly in myocardial infarction, reperfusion injury, and heart failure. Over the past two decades, investigations of several pathways have broadened our understanding of programmed cell death. Many anti-apoptotic interventions have targeted ischemia-reperfusion, however only a limited number have been considered at the chronic stage of heart failure. Endogenous inhibitors, caspase inhibitors, PARP-1 inhibitors, as well as various other agents have been implicated as anti-apoptotic interventions. This review summarizes the apoptotic pathways associated with heart failure, discusses the current anti-apoptotic interventions available and reviews the clinical implications.

Topics: Apoptosis; Cardiovascular Agents; Gene Expression Regulation; Heart Diseases; Humans

Topics: Algorithms; Cardiovascular Agents; Chromosome Aberrations; Female; Heart Diseases; Humans; Male; Middle Aged; Myotonic Dystrophy; Young Adult

Drug-induced cardiac toxicity is a recognized challenge in development and implementation of pharmacotherapy. Appropriate biomarkers are needed to detect these abnormalities early in development and to manage the risk of potentially cardiotoxic drugs or biologic agents. Circulating cardiac troponin (cTn) is the most widely used biomarker for detection of myocardial injury. Although most commonly used to detect myonecrosis in the setting of ischemia, cTns are also elevated with other acute and chronic disease processes, including heart failure, renal failure, sepsis, pulmonary embolic disease, and many others. High-sensitivity assays for both cTnI and cTnT are now available that achieve acceptable imprecision (coefficient of variation <10%) at the 99th percentile of a normal reference population. Even more sensitive assays are being developed that detect cTn in ranges that are near the level of normal cellular turnover (apoptosis). These properties of cTn and the continuing evolution of highly sensitive assays position cTn as a potentially uniquely informative marker for early detection of cardiac toxicity. This article summarizes collaborative discussions among key stakeholders in the Cardiac Safety Research Consortium about the use of cTn monitoring in drug development.

Topics: Animals; Biomedical Research; Cardiovascular Agents; Drug Evaluation; Education, Medical, Continuing; Heart; Heart Diseases; Humans; Troponin; United States; United States Food and Drug Administration

Methylxanthines, such as theophylline, have been used to treat cardiorespiratory disorders, whereas caffeine is the most widely consumed psychoactive agent in various soft drinks. Because of the worldwide use of these drugs and the recently synthesized xanthine derivatives, an intensive research on the cardiac actions of these substances is under progress. This review focuses on the molecular mechanisms involved in the actions of xanthine derivatives with special reference to their adenosine receptor antagonistic properties. The main basic and human studies on the action of xanthines on impulse initiation and conduction, as well as the electrophysiological and mechanical activity of the working myocardium will be overviewed. The potential beneficial and harmful actions of the methylxanthines will be discussed in light of the recent experimental and clinical findings. The pharmacological features and clinical observations with adenosine receptor subtype-specific xanthine antagonists are also the subject of this paper. Based on the adenosine receptor-antagonistic activity of these compounds, it can be raised that xanthine derivatives might inhibit the cardioprotective action of endogenous adenosine on various subtypes (A(1), A(2A), A(2B) and A(3)) of adenosine receptors. Adenosine is an important endogenous substance with crucial role in the regulation of cardiac function under physiological and pathological conditions (preconditioning, postconditioning, ischemia/reperfusion injury). Recent clinical studies show that acute administration of caffeine or theophylline can inhibit various types of preconditioning in human subjects. There are no human studies, however, for the cardiovascular actions of long-term administration of these drugs. Upregulation of adenosine receptors and increased effectiveness of adenosine receptor-related cardiovascular functions have been observed after long-lasting treatment with methylxanthines. In addition, there are data indicating that blood adenosine level increases after long-term caffeine administration. Since the salutary actions (and also the adverse reactions) of a number of xanthine derivatives are repeatedly shown, the main goal is the development of novel structures that mimic the actions of the conventional methylxanthines as lead compounds, but their adenosine receptor subtype-specificity is higher, their water solubility is optimal, and the unwanted reactions are minimized.

Topics: Action Potentials; Animals; Caffeine; Cardiovascular Agents; Clinical Trials as Topic; Heart Diseases; Humans; Purinergic P1 Receptor Antagonists; Receptors, Purinergic P1; Xanthines

Persons aged 65 years or older, often referred to as the elderly, are a rapidly increasing population in the United States. Cardiovascular disease is the most common cause of morbidity and death in this age group, and acute coronary syndrome accounts for a significant proportion of the deaths. Percutaneous coronary intervention is a well-established treatment for acute coronary syndrome and symptomatic coronary artery disease. However, community studies have shown that elderly patients are less likely to undergo revascularization, perhaps due to a "treatment-risk" paradox: elderly patients-at higher risk of morbidity and death from acute coronary syndrome-are denied revascularization even though they are likely to benefit from it. Age alone is one of the many reasons why percutaneous coronary intervention is avoided in elderly patients. This review examines past clinical trials and the existing evidence that supports performing percutaneous coronary intervention in elderly patients.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Evidence-Based Medicine; Heart Diseases; Humans; Myocardial Infarction; Patient Selection; Risk Assessment; Risk Factors; Treatment Outcome

The pleiotropic cyclic nucleotide cAMP is the primary second messenger responsible for autonomic regulation of cardiac inotropy, chronotropy, and lusitropy. Under conditions of prolonged catecholaminergic stimulation, cAMP also contributes to the induction of both cardiac myocyte hypertrophy and apoptosis. The formation of localized, multiprotein complexes that contain different combinations of cAMP effectors and regulatory enzymes provides the architectural infrastructure for the specialization of the cAMP signaling network. Scaffolds that bind protein kinase A are called "A-kinase anchoring proteins" (AKAPs). In this review, we discuss recent advances in our understanding of how PKA is compartmentalized within the cardiac myocyte by AKAPs and how AKAP complexes modulate cardiac function in both health and disease.

Topics: A Kinase Anchor Proteins; Animals; Cardiovascular Agents; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Heart Diseases; Humans; Myocardium; Second Messenger Systems

This review examines how the sympathetic nervous system plays a major role in the regulation of cardiovascular function over multiple time scales. This is achieved through differential regulation of sympathetic outflow to a variety of organs. This differential control is a product of the topographical organization of the central nervous system and a myriad of afferent inputs. Together this organization produces sympathetic responses tailored to match stimuli. The long-term control of sympathetic nerve activity (SNA) is an area of considerable interest and involves a variety of mediators acting in a quite distinct fashion. These mediators include arterial baroreflexes, angiotensin II, blood volume and osmolarity, and a host of humoral factors. A key feature of many cardiovascular diseases is increased SNA. However, rather than there being a generalized increase in SNA, it is organ specific, in particular to the heart and kidneys. These increases in regional SNA are associated with increased mortality. Understanding the regulation of organ-specific SNA is likely to offer new targets for drug therapy. There is a need for the research community to develop better animal models and technologies that reflect the disease progression seen in humans. A particular focus is required on models in which SNA is chronically elevated.

Topics: Animals; Cardiovascular Agents; Heart Diseases; Humans; Hypertension; Sympathetic Nervous System

Both cardio- and microvascular complications adversely affect the life quality of patients with diabetes and have been the leading cause of mortality and morbidity in this population. Cardiovascular pathologies of diabetes have an effect on microvenules, arteries, and myocardium. It is believed that hyperglycemia is one of the most important metabolic factors in the development of both micro- and macrovascular complications in diabetic patients. Several prominent hypotheses exist to explain the adverse effect of hyperglycemia. One of them is the chronic activation by hyperglycemia of protein kinase (PK)C, a family of enzymes that are involved in controlling the function of other proteins. PKC has been associated with vascular alterations such as increases in permeability, contractility, extracellular matrix synthesis, cell growth and apoptosis, angiogenesis, leukocyte adhesion, and cytokine activation and inhibition. These perturbations in vascular cell homeostasis caused by different PKC isoforms (PKC-alpha, -beta1/2, and PKC-delta) are linked to the development of pathologies affecting large vessel (atherosclerosis, cardiomyopathy) and small vessel (retinopathy, nephropathy and neuropathy) complications. Clinical trials using a PKC-beta isoform inhibitor have been conducted, with some positive results for diabetic nonproliferative retinopathy, nephropathy, and endothelial dysfunction. This article reviews present understanding of how PKC isoforms cause vascular dysfunctions and pathologies in diabetes.

Topics: Animals; Blood Glucose; Cardiovascular Agents; Diabetes Complications; Diabetic Angiopathies; Diglycerides; Endothelium, Vascular; Enzyme Activation; Heart Diseases; Humans; Isoenzymes; Protein Kinase C; Protein Kinase Inhibitors; Signal Transduction

Fibrosis is one of the largest groups of diseases for which there is no therapy but is believed to occur because of a persistent tissue repair program. During connective tissue repair, "activated" fibroblasts migrate into the wound area, where they synthesize and remodel newly created extracellular matrix. The specialized type of fibroblast responsible for this action is the alpha-smooth muscle actin (alpha-SMA)-expressing myofibroblast. Abnormal persistence of the myofibroblast is a hallmark of fibrotic diseases. Proteins such as transforming growth factor (TGF)beta, endothelin-1, angiotensin II (Ang II), connective tissue growth factor (CCN2/CTGF), and platelet-derived growth factor (PDGF) appear to act in a network that contributes to myofibroblast differentiation and persistence. Drugs targeting these proteins are currently under consideration as antifibrotic treatments. This review summarizes recent observations concerning the contribution of TGFbeta, endothelin-1, Ang II, CCN2, and PDGF and to fibroblast activation in tissue repair and fibrosis and the potential utility of agents blocking these proteins in affecting the outcome of cardiac fibrosis.

Topics: Angiotensin II; Animals; Cardiovascular Agents; Connective Tissue Growth Factor; Drug Design; Endothelin-1; Extracellular Matrix Proteins; Fibroblasts; Fibrosis; Heart Diseases; Humans; Myocardium; Platelet-Derived Growth Factor; Signal Transduction; Transforming Growth Factor beta

Cardiotoxicity and extravasation injuries are extremely serious complications of anthracycline use. Both complications are probably caused by oxidative stress. Dexrazoxane has been approved as a cardioprotective agent and as an antidote in extravasation of anthracyclines. Randomized clinical trials have shown that dexrazoxane is the only cardioprotective agent proven to be effective in the treatment of anthracycline-induced cardiotoxicity. In these clinical studies dexrazoxane decreased the incidence of cardiac events and heart failure. Possible adverse effects of dexrazoxane when administered as a cardioprotective agent are a decreased antitumor effect of anthracyclines and the onset of secondary malignancies in children. As an antidote in anthracycline extravasation, clinical studies showed dexrazoxane to be highly efficacious in preventing the need for surgical resection. Dexrazoxane can be considered as the treatment of first choice for this indication. Dexrazoxane is well tolerated in general. The most commonly reported side effects are leukopenia, thrombocytopenia and local reactions at the infusion site.

Topics: Anthracyclines; Cardiovascular Agents; Heart Diseases; Heart Failure; Humans; Randomized Controlled Trials as Topic; Razoxane

One of the most powerful regulators of cardiovascular function is catecholamine-stimulated adrenergic receptor (AR) signaling. The failing heart is characterized by desensitization and impaired beta-AR responsiveness as a result of upregulated G protein-coupled receptor kinase-2 (GRK2) present in injured myocardium. Deterioration of cardiac function is progressively enhanced by chronic adrenergic over-stimulation due to increased levels of circulating catecholamines. Increased GRK2 activity contributes to this pathological cycle of over-stimulation but lowered responsiveness. Over the past two decades the GRK2 inhibitory peptide betaARKct has been identified as a potential therapy that is able to break this vicious cycle of self-perpetuating deregulation of the beta-AR system and subsequent myocardial malfunction, thus halting development of cardiac failure. The betaARKct has been shown to interfere with GRK2 binding to the betagamma subunits of the heterotrimeric G protein, therefore inhibiting its recruitment to the plasma membrane that normally leads to phosphorylation and internalization of the receptor. In this article we summarize the current data on the therapeutic effects of betaARKct in cardiovascular disease and report on recent and ongoing studies that may pave the way for this peptide towards therapeutic application in heart failure and other states of cardiovascular disease.

Topics: Animals; Cardiovascular Agents; Disease Models, Animal; G-Protein-Coupled Receptor Kinase 2; Genetic Therapy; Heart Diseases; Heart-Assist Devices; Humans; Molecular Targeted Therapy; Myocardium; Peptides; Protein Kinase Inhibitors; Receptors, Adrenergic, beta; Recombinant Proteins; Signal Transduction; Translational Research, Biomedical

Quality improvement in cardiology over the past decade focused on management of acute coronary syndrome with invasive and innovative medical therapies, optimizing treatment of congestive heart failure and the development of repair procedures in valvular heart disease. On the other hand cardiologist and the attendant physicians are confronted with changes in the characteristics of patients in the light of demographic facts. Comorbidity and polypharmacy raise the need for clear concepts. Therapeutic and diagnostic tools of geriatric medicine may help in that context.

Topics: Aged; Aged, 80 and over; Bradycardia; Cardiovascular Agents; Drug Interactions; Drug Therapy, Combination; Frail Elderly; Heart Diseases; Humans; Long QT Syndrome; Prescription Drugs; Syncope; Tachycardia

Cardiac involvement is undeniably one of the most challenging issues in sarcoidosis. Although autopsy studies reveal heart lesions in 20 to 30% of sarcoid patients, fewer than 5% suffer from clinical disease. Cardiac sarcoidosis (CS) has a predilection for the myocardium, but the pericardium and endocardium may also be affected. CS manifestations are various and most frequently include the following: (1) aberrations of atrioventricular or intraventricular conduction, either silent or symptomatic; (2) ventricular arrhythmias; (3) subacute congestive heart failure; and (4) sudden death. CS must be detected in all sarcoid patients by means of detailed medical history, physical examination, and resting electrocardiogram (ECG) at first evaluation and during follow-up. In patients with suspected CS, further investigations are aimed at evaluating diagnosis and cardiac consequences. Unfortunately, no gold standard exists that would allow CS diagnosis with a level of confidence. Endomyocardial biopsy is an invasive procedure that lacks sensitivity. Patients need, at a minimum, specialized cardiologic advice, echocardiography, and 24-hour ambulatory ECG. Other diagnostic tools include thallium, technetium, and gallium scintigraphy, and more recently, 18F-fluorodeoxyglucose positron emission tomography and cardiac magnetic resonance (CMR). The respective role of these new imaging tools in the diagnostic approach remains to be defined. CMR has the advantage of not exposing patients to radiation, but it is not feasible in those with cardiac devices. In Western countries, heart involvement accounts for 13 to 25% of sarcoidosis-related deaths, and it is the leading cause of mortality in Japan. The main prognostic indicators are New York Heart Association functional class, left ventricular enlargement, and sustained ventricular tachycardia. Treatment is based on systemic corticosteroids with an initial dose between 30 mg/day and 1 mg/kg/day (which is usually maintained for at least 24 months), specific cardiologic agents, and the placement of a pacemaker or implantable cardiac defibrillator in case of an atrioventricular block or severe intractable ventricular arrhythmias. Cardiac transplantation is exceptionally required.

Topics: Biopsy; Cardiovascular Agents; Echocardiography; Electrocardiography, Ambulatory; Glucocorticoids; Heart Diseases; Heart Transplantation; Humans; Magnetic Resonance Imaging; Positron-Emission Tomography; Sarcoidosis

Recent experimental data suggest glucagon-like peptide 1 (GLP-1) and its analogs to have direct effects on the cardiovascular system, in addition to their classic glucoregulatory actions. These direct effects may be cardioprotective, contractility augmenting, and vasorelaxant. A few preliminary clinical trials appear to support a mechanical function improvement after GLP-1 administration to patients with a weakened left ventricle. Based on animal studies, diminished lethal injury to the postischemic reperfused myocardium appears to be a particularly promising prospect, awaiting to be tested in clinical settings.

Topics: Animals; Blood Pressure; Cardiovascular Agents; Glucagon-Like Peptide 1; Heart Diseases; Humans; Myocardial Contraction; Myocardial Reperfusion Injury; Signal Transduction; Treatment Outcome; Vasodilation; Ventricular Function, Left

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

An understanding of onco-cardiology or cardio-oncology is critical for the effective care of cancer patients. Virtually all antineoplastic agents are associated with cardiotoxicity, which can be divided into 5 categories: direct cytotoxic effects of chemotherapy and associated cardiac systolic dysfunction, cardiac ischemia, arrhythmias, pericarditis, and chemotherapy-induced repolarization abnormalities. Radiation therapy can also lead to coronary artery disease and fibrotic changes to the valves, pericardium, and myocardium. All patients being considered for chemotherapy, especially those who have prior cardiac history, should undergo detailed cardiovascular evaluation to optimize the treatment. Serial assessment of left ventricular systolic function and cardiac biomarkers might also be considered in selected patient populations. Cardiotoxic effects of chemotherapy might be decreased by the concurrent use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or beta-blockers. Antiplatelet or anticoagulation therapy might be considered in patients with a potential hypercoagulable state associated with chemotherapy or cancer. Open dialogue between both cardiologists and oncologists will be required for optimal patient care.

Topics: Anticoagulants; Antineoplastic Agents; Cardiology; Cardiovascular Agents; Cooperative Behavior; Heart Diseases; Heart Function Tests; Humans; Medical Oncology; Patient Care Team; Predictive Value of Tests; Radiation Injuries; Thrombophilia

Curcumin (diferuoylmethane) is the active ingredient of turmeric (curcuma longa). There has been a surge of research in its anti-inflammatory and antioxidative properties, and its cardiovascular effects. A host of studies in in vitro and in vivo models of cardiac injury show that curcumin treatment reduces reactive oxygen species generation, monocyte adhesion to activated endothelial cells, and phosphorylation of c-Jun N-terminal kinase, p38 mitogen activated protein kinase and signal transducer and activator of transcription-3, and subsequent downstream signals. These alterations lead to preservation of myocardial function following ischemic or biochemical insult to the heart. Recent studies in models of pressure overload show that curcumin can reduce cardiac remodeling by altering reninangiotensin-system-transforming growth factor beta1 and collagen axis. Studies need to be done in humans to define the potential of curcumin in limitation of cardiac injury and preservation of cardiac function following ischemia.

Topics: Adrenergic beta-Agonists; Animals; Antibiotics, Antineoplastic; Cardiovascular Agents; Curcumin; Doxorubicin; Endothelium, Vascular; Heart Diseases; Humans; Isoproterenol; Muscle, Smooth, Vascular; Myocardial Reperfusion Injury; Myocytes, Cardiac; Oxidative Stress; Signal Transduction

Cardioembolic stroke accounts for one third of all ischemic strokes, and atrial fibrillation (AF) is the cardiac source of emboli in 50% of them. However, the absolute risk of stroke associated with AF has enormous variability, and several clinical risk stratification schemes have been proposed. One of the most validated and used in clinical practice is the CHADS2 index, characterized by its simplicity and rapid application. Current recommendations about antithrombotic therapy in AF patients are based on assessment of annual risk of stroke; thus, antiaggregation is indicated in patients with a low risk, and anticoagulation is prescribed when annual risk is greater than 2.5%. Relevant studies comparing rate and rhythm control do not defend achievement and maintenance of sinus rhythm as a routine management of AF patients and demonstrate that rate control is comparable or even better than rhythm control in terms of survival and quality of life. Optimal control of blood pressure is a relevant factor in preventing cardioembolic stroke in AF patients, because hypertension multiplies the risk of stroke by 12. Antihypertensive drugs such as angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers proved to reduce AF recurrences, especially in the context of left ventricular dysfunction and ventricular hypertrophy.

Topics: Anti-Arrhythmia Agents; Anticoagulants; Antihypertensive Agents; Atrial Fibrillation; Cardiovascular Agents; Embolism; Fibrinolytic Agents; Heart Diseases; Humans; Hypertension; Patient Care Team; Patient Selection; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Risk Assessment; Risk Factors; Secondary Prevention; Stroke; Treatment Outcome

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

The indications and doses of most drugs used for heart ailments in children are extrapolated from data in adult patients. Separate guidelines are needed for neonates, infants and children because of the differences in underlying heart diseases and metabolic clearance of some of these drugs.. Consensus emerged following expert deliberations at the National Meeting on Management of Congenital Heart Diseases in India, held on 13th September 2008, at the All India Institute of Medical Sciences, New Delhi, India, supported by Pediatric Cardiac Society of India.. To review the literature and frame evidence based guidelines for (i) indications, doses, adverse effects and safety profile of commonly used drugs in pediatric cardiology practice; and (ii) to provide an algorithm for treatment in various clinical settings.. Consensus review and recommendations are given for drugs used in children for heart failure, hypertension, thrombosis, supraventricular tachycardia and intensive care. Guidelines are also given for use of intravenous immunoglobulins and sildenafil in children.

Topics: Cardiovascular Agents; Child; Child, Preschool; Heart Diseases; Humans; Infant; Infant, Newborn

This review presents 201 compounds isolated and identified from plants that present cardioactive activity. These substances have been classified by chemical groups and each provides the most relevant information of its pharmacological activity, action mechanism, chemical structure, spectroscopic date and other properties. Chemical structures have been drawn to indicate the stereochemistry. In this review the summary of the scientific information of plants that present biological activity and the compounds responsible for this activity is presented, which introduces the reader to the study of medicinal plants and also provide bibliographic references, where a detailed study of pharmacology can be found.

Topics: Animals; Cardiovascular Agents; Heart Diseases; Humans; Plant Extracts; Plants; Plants, Medicinal

Classical non-insulin antihyperglycemic drugs currently approved for the treatment of type 2 diabetes mellitus (T2DM) comprise five groups: biguanides, sulfonylureas, meglitinides, glitazones and alpha-glucosidase inhibitors. Novel compounds are represented by the incretin mimetic drugs like glucagon like peptide-1 (GLP-1), the dipeptidyl peptidase 4 (DPP-4) inhibitors, dual peroxisome proliferator-activated receptors (PPAR) agonists (glitazars) and amylin mimetic drugs. We review the cardiovascular effects of these drugs in an attempt to improve knowledge regarding their potential risks when treating T2DM in cardiac patients. Metformin may lead to lethal lactic acidosis, especially in patients with clinical conditions that predispose to this complication, such as recent myocardial infarction, heart or renal failure. Sulfonylureas exert their effect by closing the ATP-dependent potassium channels. This prevents the opening of these channels during myocardial ischemia, impeding the necessary hyperpolarization that protects the cell. The combined sulfonylurea/metformin therapy reveals additive effects on mortality in patients with coronary artery disease (CAD). Meglitinides effects are similar to those of sulfonylureas, due to their almost analogous mechanism of action. Glitazones lower leptin levels, leading to weight gain and are unsafe in NYHA class III or IV. The long-term effects of alpha-glucosidase inhibitors on morbidity and mortality rates is yet unknown. The incretin GLP-1 is associated with reductions in body weight and appears to present positive inotropic effects. DPP-4 inhibitors influences on the cardiovascular system seem to be neutral and patients do not gain weight. The future of glitazars is presently uncertain following concerns about their safety. The amylin mimetic drug paramlintide, while a satisfactory adjuvant medication in insulin-dependent diabetes, is unlikely to play a major role in the management of T2DM. Summarizing the present information it can be stated that 1. Four out the five classical oral antidiabetic drug groups present proven or potential cardiac hazards; 2. These hazards are not mere 'side effects', but biochemical phenomena which are deeply rooted in the drugs' mechanism of action; 3. Current data indicate that the combined glibenclamide/metformin therapy seems to present special risk and should be avoided in the long-term management of T2DM with proven CAD; 4. Glitazones should be avoided in patients with overt he

Topics: Animals; Cardiovascular Agents; Diabetes Mellitus, Type 2; Heart Diseases; Humans; Hypoglycemic Agents; Insulin; Survival Rate

Chronic kidney disease is common in patients with chronic heart failure and has important clinical implications. The coexistence of these two syndromes is associated with a higher risk of adverse outcome and increases the difficulties of heart failure treatment because of the complex interplay between renal dysfunction and pharmacologic therapy. The underrepresentation of patients with chronic kidney disease in most heart failure trials contributes to the suboptimal treatment of this high-risk population in clinical practice. In the present review, we briefly examine the pathophysiologic mechanisms connecting chronic kidney disease and chronic heart failure and discuss the therapeutic approach to patients affected by both conditions.

Topics: Cardiovascular Agents; Chronic Disease; Heart Diseases; Humans; Kidney; Kidney Diseases; Kidney Function Tests; Treatment Outcome

Brain natriuretic peptide (BNP) plays an important role in cardiovascular homeostasis. Plasma BNP increases markedly in left ventricular dysfunction from several causes, and its levels in heart failure (HF) correlate with symptoms severity. BNP has recently emerged as a potentially important clinical marker for the diagnosis of HF in patients with unexplained dyspnea. Other clinical applications of BNP, such as screening for asymptomatic ventricular dysfunction, establishing the prognosis or guiding the titration of drug therapy, are under investigation and have not yet been sufficiently validated for widespread clinical use. Laboratory-based and point-of-care analyses are available for BNP and N-terminal proBNP as fully-automated immunoassays. Several patented inventions and reagents for the diagnosis of various heart pathologies provide helpful information, particularly in conjunction with other clinical tests. They also have prognostic value for future cardiovascular events. Patents owned by Scios Inc. recommended recombinant BNP for managing acute decompensated HF. However, this treatment apparently has safety problems and no proven clinical advantage over existing treatments in terms of improved survival and prevention of subsequent hospitalizations.

Topics: Amino Acid Sequence; Biomarkers; Cardiovascular Agents; Heart Diseases; Humans; Immunoassay; Molecular Sequence Data; Natriuretic Peptide, Brain; Patents as Topic; Peptide Fragments; Point-of-Care Systems; Prognosis; Reagent Kits, Diagnostic; Recombinant Proteins; Treatment Outcome

In various cardiac diseases, thrombembolism constitutes a major risk, and in these patients clinically silent microembolic signals (MES) are detectable within the transcranial Doppler frequency spectrum (TCD) of the major brain arteries. MES are already an accepted surrogate parameter of the future risk of stroke in patients with carotid artery stenosis. The aim of this review is to summarize and evaluate the data about occurence and clinical impact of MES in patients with chronic cardiac diseases and to clarify whether cardiogenic MES can serve as a surrogate parameter of the heart's future thrombembolic risk as well.. We performed a systematic MEDLINE search and reviewed the currently available literature about chronic cardiac diseases and atheroaortic plaques leading to MES apart from cardiosurgical procedures.. The cardiac conditions producing MES are heterogenous and therefore the prevalence of MES is highly variable. The data in patients with acute or after myocardial infarction, endocarditis, patent foramen ovale, mitral valve prolapse, dilatative cardiomyopathy and intracardiac thrombus is promising but only small patient cohorts have been investigated by means of TCD in these categories. MES in atrial fibrillation, or derived from atheroaortic plaques, have been investigated more intensively, but again larger cohorts need to be explored to draw firm conclusions. In all cardiac diseases there is a lack of large prospective studies allowing to reliably correlating MES with clinical events. Compared to carotid artery disease, the current knowledge about the impact of cardiogenic MES on the patient's risk is sparse. This should encourage the clinical research in this promising field.

Topics: Aortic Diseases; Atherosclerosis; Cardiovascular Agents; Chronic Disease; Heart Diseases; Humans; Intracranial Embolism; Risk Factors; Ultrasonography, Doppler, Transcranial

Patients undergoing vascular surgery are at increased risk for cardiac complications related to the presence of underlying coronary artery disease. Preoperative cardiac evaluation may help to identify high-risk patients in whom coronary angiography may be planned with subsequent coronary revascularization for the purpose of improving perioperative and long-term cardiac outcomes. However, the indications and efficacy for type of revascularization for the reduction of cardiac complications compared to medical therapy has been controversial. My aim in this review is to summarize the role of preoperative revascularization compared to conservative medical therapy before elective vascular surgery using current evidence from published studies.

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Bypass; Coronary Artery Disease; Echocardiography; Elective Surgical Procedures; Heart Diseases; Humans; Patient Selection; Practice Guidelines as Topic; Preoperative Care; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Severity of Illness Index; Treatment Outcome; Vascular Surgical Procedures

Unlike other CDKs, CDK9 does not regulate the cell cycle but promotes RNA synthesis in genetic programmes for cell growth, differentiation and viral pathogenesis. It is becoming clear that CDK9 inhibition contributes to the anticancer activity of most CDK inhibitors under clinic investigation. CDK9 was discovered in the context of HIV research because retroviruses hijack host transcription and CDK9 inhibitors might become specific antiretroviral agents, particularly as they might prevent drug resistance. Myocardial hypertrophy is a risk factor in congestive heart failure and is characterised by derepressed CDK9 activity. CDK9 inhibitors, thus, can find therapeutic application in cardiology. Although there are strong signs that CDK9 inhibition would be a useful therapeutic strategy in all three indications, the lack of selective inhibitors has so far confounded clinical development. Here we give an overview of the validity of CDK9 as a drug target and of the current knowledge of this kinase and its inhibitors.

Topics: Animals; Antineoplastic Agents; Antiviral Agents; Cardiovascular Agents; Cyclin-Dependent Kinase 9; Drug Delivery Systems; Heart Diseases; Humans; Neoplasms; Virus Diseases

The development of a number of regenerative strategies in recent years for curing heart disease represents a paradigm shift away from conventional approaches which aim to manage heart disease. Effective administration of pharmaceutical agents targeted directly to the diseased tissue is the key to unlocking the potential of regenerative strategies, which could augment current conventional treatments.. The authors review recent advances in targeted drug delivery to diseased cardiac tissue.. Various therapeutic methodologies designed to selectively deliver pharmaceutical agents to diseased cardiac tissue are discussed in this review.. Targeted delivery of survival and engraftment promoting factors to damaged cardiac tissue can be an important strategy, for example, in creating a suitable microenvironment encouraging the engraftment of stem cells. Further progress in this emerging field is contingent on the discovery of new biomarkers that are upregulated in damaged cardiac tissue and can be targeted for selective drug delivery. Once fully realized, breakthroughs in this field will have direct applications in the diagnosis and treatment of heart disease through more effective tissue-specific drug delivery and improved imaging modalities.

Topics: Animals; Cardiovascular Agents; Drug Carriers; Drug Delivery Systems; Heart Diseases; Humans; Myocardium; Stem Cell Transplantation; Ultrasonics

Trimetazidine (TMZ) is an effective and well-tolerated antianginal drug that possesses protective properties against ischemia-induced heart injury. Growing interest in metabolic modulation in recent years urged an up-to-date review of the literature on TMZ. This review consists of two major sections: (1) comprehensive and critical information about the pharmacological effects, mechanism of action, pharmacokinetics, side effects, and current usage of TMZ, and (2) developments in analytical techniques for the determination of the drug in raw material, pharmaceutical dosage forms, and biological samples.

Topics: Animals; Antioxidants; Cardiovascular Agents; Chemistry Techniques, Analytical; Chromatography; Coronary Circulation; Coronary Vessels; Electrochemistry; Energy Metabolism; Flow Injection Analysis; Heart Diseases; Humans; Ischemia; Luminescent Measurements; Myocardial Contraction; Myocardium; Reactive Oxygen Species; Spectrophotometry; Trimetazidine

Sudden cardiac death (SCD) is the most common cause of death and often occurs in low-risk patients. Present prevention strategies, mainly confined to high-risk subjects (proposed implantable cardioverter defibrillators recipients), have a limited effect on SCD burden in the general population. A relatively unexplored strategy for extending SCD prevention could imply targeting the early (upstream) processes of the complex cascade leading to SCD by non-antiarrhythmic drugs (i.e., beta-blockers, aldosterone antagonists, angiotensin-converting enzyme inhibitors, angiotensin receptor-blocker agents, statins and omega-3 fatty acids). In this innovative pharmacological perspective, agents with upstream effects may also be used in high-risk patients in association with a strictly downstream intervention, such as the implantable cardioverter defibrillator, in an attempt to obtain an additive/synergetic effect.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Combined Modality Therapy; Death, Sudden, Cardiac; Defibrillators, Implantable; Fatty Acids, Omega-3; Heart Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mineralocorticoid Receptor Antagonists

The phospholipases associated with the cardiac sarcolemmal (SL) membrane hydrolyze specific membrane phospholipids to generate important lipid signaling molecules, which are known to influence normal cardiac function. However, impairment of the phospholipases and their related signaling events may be contributory factors in altering cardiac function of the diseased myocardium. The identification of the changes in such signaling systems as well as understanding the contribution of phospholipid-signaling pathways to the pathophysiology of heart disease are rapidly emerging areas of research in this field. In this paper, I provide an overview of the role of phospholipid-mediated signal transduction processes in cardiac hypertrophy and congestive heart failure, diabetic cardiomyopathy, as well as in ischemia-reperfusion. From the cumulative evidence presented, it is suggested that phospholipid-mediated signal transduction processes could serve as novel targets for the treatment of the different types of heart disease.

Topics: Animals; Cardiomegaly; Cardiomyopathies; Cardiovascular Agents; Diabetes Complications; Enzyme Inhibitors; Heart Diseases; Heart Failure; Humans; Myocardial Reperfusion Injury; Myocardium; Phospholipases; Phospholipids; Sarcolemma; Signal Transduction

Although effective anti-neoplastic agents, anthracyclines are limited by their well recognized and pervasive cardiotoxic effects. The incidence of late progressive cardiovascular disease in long-term survivors of cancer is established and may contribute to heart failure and death. To maximize the benefits of these drugs, a high-risk population has been identified and new strategies have been investigated to minimize toxic effects, including limiting the cumulative dose, controlling the rate of administration and using liposomal preparations and novel anthracycline analogues. Dexrazoxane also shows promise as a cardioprotectant during treatment. This paper reviews these strategies, as well as medications used to manage anthracycline-induced cardiotoxicity, and functional and biochemical means of monitoring cardiotoxicity, including echocardiography, radionuclide scans and biomarker analysis. The treatment of adult cancer survivors who have had anthracycline-related cardiotoxicity has not been systematically studied. Empirically, anthracycline-associated cardiac dysfunction is treated very similarly to other forms of heart failure. These treatments include avoiding additional cardiotoxic regimens, controlling hypertension, lifestyle changes, medications and heart transplantation.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Cardiovascular Agents; Drug Interactions; Drug Monitoring; Heart; Heart Diseases; Humans; Neoplasms; Razoxane; Risk Factors

To evaluate the technologies used to reduce anthracycline-induced cardiotoxicity in children. Also to evaluate cardiac markers to quantify cardiotoxicity, and identify cost-effectiveness studies and future research priorities.. Eight electronic databases were searched from inception to January 2006. Bibliographies of related papers were assessed for relevant studies and experts contacted to identify additional published references.. A systematic review of the evidence was undertaken using a priori methods.. Four randomised controlled trials (RCTs) met the inclusion criteria of the review, each considering a different cardioprotective intervention; all trials included children with acute lymphoblastic leukaemia, and one also included children with non-Hodgkin's lymphoma. However, all had methodological limitations. No cost-effectiveness studies were identified. One RCT and six cohort studies on the use of cardiac markers met the inclusion criteria of the review, but also had methodological limitations. Of the two RCTs that considered continuous infusion versus bolus (rapid) infusion, one found that continuous infusion of doxorubicin did not offer any cardioprotection over bolus; the other suggested that continuous infusion of daunorubicin had less cardiotoxicity than bolus. Two studies considered cardioprotective agents, one concluded that dexrazoxane prevents or reduces cardiac injury without compromising the antileukaemic efficacy of doxorubicin and the other reported a protective effect of coenzyme Q10 on cardiac function during anthracycline therapy. One RCT suggested that cardiac troponin T can be used to assess the effectiveness of the cardioprotective agent dexrazoxane. Two cohort studies considering atrial natriuretic peptide and two considering brain (B-type) natriuretic peptide suggested that these chemicals are elevated in some subgroups of children treated with anthracyclines for cancer. N-terminal B-type natriuretic peptide levels were significantly elevated in children treated with anthracyclines who had cardiac dysfunction. One cohort study found that serum lipid peroxide was higher in younger children treated with doxorubicin than correspondingly aged children not receiving doxorubicin. No differences in carnitine levels were found in children treated with doxorubicin and a group of healthy children in one cohort study.. It is difficult to draw conclusions about the effectiveness of technologies for reducing or preventing cardiotoxicity and about the use of cardiac markers in children as the evidence is limited in quantity and quality. The lack of standardisation for monitoring and reporting cardiac performance is problematic. Not all studies report effectiveness in terms of cardiac outcomes and event-free survival with supporting statistical analyses. Studies are mostly small and of short duration, making generalisation difficult. Increasing numbers of survivors of childhood cancer treated with anthracyclines will experience cardiac damage and require long-term surveillance and management. This will have an impact on cardiac services and costs. Diverse medical problems and other late sequelae that affect cardiac outcome will have an impact on other specialist services. Mechanisms to reduce or prevent cardiotoxicity from anthracycline therapy and cardiac markers to improve monitoring could alter the extent of this impact on service provision. RCTs of the different methods for reducing or preventing cardiotoxicity in children treated with anthracyclines for cancer with long-term follow-up are needed to determine whether the technologies influence the development of cardiac damage. Cost-effectiveness research is also required.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Biomarkers; Cardiovascular Agents; Child; Drug Administration Schedule; Heart Diseases; Heart Failure; Humans; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Dexrazoxane is highly effective in reducing anthracycline-induced cardiotoxicity and extravasation injury and is used clinically for these indications. Dexrazoxane has two biological activities: it is a prodrug that is hydrolyzed to an iron chelating EDTA-type structure and it is also a strong inhibitor of topoisomerase II. Doxorubicin is able to be reductively activated to produce damaging reactive oxygen species. Iron-dependent cellular damage is thought to be responsible for its cardiotoxicity. The available experimental evidence supports the conclusion that dexrazoxane reduces doxorubicin cardiotoxicity by binding free iron and preventing site-specific oxidative stress on cardiac tissue. However, it cannot be ruled out that dexrazoxane may also be protective through its ability to inhibit topoisomerase II.

Topics: Animals; Antineoplastic Agents; Cardiovascular Agents; Clinical Trials as Topic; Doxorubicin; Enzyme Inhibitors; Heart Diseases; Humans; Neoplasms; Prodrugs; Razoxane; Topoisomerase II Inhibitors

Dexrazoxane has been in clinical use for more than 25 years for prevention of cardiotoxicity in anthracycline based anticancer therapy. However, we discovered another property of the compound, i.e. the ability to prevent the devastating tissue necrosis after accidental extravasation of anthracyclines. The preclinical and clinical studies leading to the clinical implementation of Savene (dexrazoxane) as the first and only proven antidote in anthracycline extravasation are described in short.

Topics: Animals; Anthracyclines; Antibiotics, Antineoplastic; Cardiovascular Agents; Clinical Trials as Topic; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Heart Diseases; Humans; Mice; Razoxane

Activation of the transcription factor signal transducers and activators of transcription (STAT) 3 is a defining feature of the interleukin (IL)-6 family of cytokines, which include IL-6, leukemia inhibitory factor, and cardiotrophin-1. These cytokines, as well as STAT3 activation, have been shown to be protective for cardiac myocytes and necessary for ischemia preconditioning. However, the mechanisms that regulate IL-6-type cytokine signaling in cardiac myocytes are largely unexplored. We propose that the protective character of IL-6-type cytokine signaling in cardiac myocytes is determined principally by three mechanisms: redox status of the nonreceptor tyrosine kinase Janus kinase 1 (JAK) 1 that activates STAT3, phosphorylation of STAT3 within the transcriptional activation domain on serine 727, and STAT3-mediated induction of suppressor of cytokine signaling (SOCS) 3 that terminates IL-6-type cytokine signaling. Moreover, we hypothesize that hyperactivation of the JAK kinases, particularly JAK2, mismatched STAT3 serine-tyrosine phosphorylation or heightened STAT3 transcriptional activity, and SOCS3 induction may ultimately prove detrimental. Here we summarize recent evidence that supports this hypothesis, as well as additional possible mechanisms of JAK-STAT regulation. Understanding how IL-6-type cytokine signaling is regulated in cardiac myocytes has great significance for exploiting the therapeutic potential of these cytokines and the phenomenon of preconditioning.

Topics: Animals; Cardiovascular Agents; Cytokines; Drug Delivery Systems; Heart Diseases; Humans; Interleukin-6; Janus Kinase 1; Signal Transduction; STAT3 Transcription Factor; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins

The endoplasmic reticulum (ER) is a multifunctional organelle responsible for the synthesis and folding of proteins as well as calcium storage and signaling. Perturbations of ER function cause ER stress leading to the unfolded protein response (UPR), which includes inhibition of protein synthesis, protein refolding and clearance of misfolded proteins. The UPR aims at restoring cellular homeostasis, however, prolonged ER stress can trigger apoptosis. ER stress-induced apoptosis has been implicated in the pathogenesis of various diseases such as brain ischemia/reperfusion, neurodegeneration, diabetes and, most recently, myocardial infarction and heart failure. Initial events leading to UPR and apoptosis in the heart include protein oxidation and disturbed calcium handling upon ischemia/reperfusion, and forced protein synthesis during cardiac hypertrophy. While XBP-1 and ATF6-mediated induction of ER chaperones seems to protect the heart from ischemia/reperfusion injury, the PERK/ATF4/CHOP branch of the UPR might transmit proapoptotic signals. The precise mechanism of ER stress-induced cardiomyocyte apoptosis remains elusive, however, recent data suggest that the mitochondrial apoptotic machinery is recruited through the upregulation of Puma, a proapoptotic member of the Bcl-2 family. Importantly, suppression of Puma activity prevented both ER stress and ischemia/reperfusion-induced cardiomyocyte loss, highlighting the ER stress pathways as potential therapeutic targets in cardiovascular diseases.

Topics: Animals; Apoptosis; Cardiovascular Agents; Endoplasmic Reticulum; Heart Diseases; Humans; Protein Folding; Signal Transduction; Stress, Physiological

When amyloidosis affects the heart, a devastating and progressive process can lead to congestive heart failure, arrhythmias, conduction abnormalities, angina, and death. The signs and symptoms of cardiac amyloidosis are generally dominated by diastolic heart failure resulting from restrictive cardiomyopathy. Amyloid infiltration of the heart initially causes mild diastolic dysfunction, but late disease produces a thickened heart wall with a firm and rubbery consistency, which worsens cardiac relaxation and diastolic compliance. Patients usually complain of progressive dyspnea from congestive heart failure, chest discomfort secondary to microvascular involvement, and weight loss, which might be a manifestation of cardiac cachexia. Echocardiographic findings include nondilated ventricles with concentric left ventricular thickening, right ventricular thickening, prominent valves, dilated atria, and thickening of the interatrial septum. Recent advances in our understanding of the pathophysiology of amyloid have allowed the various types to be differentiated, which has led to targeted therapy for each unique pathophysiologic process.

Topics: Amyloidosis; Anti-Infective Agents; Biomarkers; Cardiac Catheterization; Cardiomyopathy, Restrictive; Cardiovascular Agents; Drugs, Investigational; Echocardiography; Electrocardiography; Heart Diseases; Heart Failure; Heart Transplantation; Humans; Liver Transplantation; Magnetic Resonance Imaging; Stem Cell Transplantation; Treatment Outcome

Statins are pluripotent agents exhibiting multiple non-lipid-lowering actions. Besides their established role in the management of hypercholesterolemia, statins may also have beneficial actions in other pathological conditions, namely: a) osteoporosis and osteoporosis-related bone fractures, b) cancer, c) solid organ transplantation, d) cerebrovascular events (transient ischemic attack and stroke episodes), e) various neurological disorders, such as Alzheimer's disease, Parkinson's disease and multiple sclerosis, f) cardiac arrhythmias and heart failure, g) renal diseases, h) rheumatoid arthritis, i) autoimmune diseases, j) sepsis, and k) allergic asthma. We reviewed the literature searching for studies that support or oppose the use of statins in each proposed indication. In some of these emerging indications, a role for statin treatment is more firmly set; for others, current evidence is more controversial. Future trials may reveal more convincing evidence that will make statin use necessary in the therapeutic management of several diseases.

Topics: Animals; Anti-Asthmatic Agents; Antineoplastic Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Asthma; Autoimmune Diseases; Bone Density Conservation Agents; Cardiovascular Agents; Cerebrovascular Disorders; Heart Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney Diseases; Neoplasms; Nervous System Diseases; Neuroprotective Agents; Organ Transplantation; Osteoporosis; Sepsis

Thirty-eight articles have been published on the association between elevated heart rate and mortality. After adjustment for other risk factors, most studies found an independent association between heart rate and all-cause and/or cardiovascular mortality. This relationship has been found to be generally weaker among females. The four studies performed in hypertensive patients found a positive association between heart rate and all-cause mortality or cardiovascular mortality. In spite of this evidence, elevated heart rate remains a neglected cardiovascular risk factor in both genders. The pathogenetic mechanisms connecting high heart rate, hypertension, atherosclerosis and cardiovascular events have also been elucidated in many studies. Several trials retrospectively showed the beneficial effect of cardiac-slowing drugs, such as beta-blockers and non-dihydropyridine calcium antagonists on mortality, notably in patients with coronary heart disease, or heart failure, but no published data are available in patients with hypertension free of coronary heart disease. Although it has not been proven in existing trials, it would seem reasonable to recommend in hypertensive subjects with heart rate > 80-85 b/min, antihypertensive agents that decrease the heart rate. The f-channel blockers, selective heart rate-lowering agents with no effect on blood pressure, could also be profitably used in hypertensive subjects with fast heart rate.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Antihypertensive Agents; Calcium Channel Blockers; Cardiovascular Agents; Clinical Trials as Topic; Coronary Artery Disease; Drug Therapy, Combination; Heart Diseases; Heart Rate; Humans; Hypertension; Risk Factors; Survival Rate; Tachycardia

The demographic trend challenges anaesthesiologists with a growing number of elderly requiring surgery. The anaesthetist needs to identify risk patients and to optimize his strategies for perioperative management. The present article gathers the current data and summarizes effective strategies for anaesthesia in patients with ischemic heart disease.

Topics: Anesthesia; Cardiovascular Agents; Heart Diseases; Humans; Intraoperative Care; Platelet Aggregation Inhibitors; Risk Assessment

Liver cirrhosis is associated with several cardiovascular disturbances. These disturbances include hyperdynamic systemic circulation, manifested by an increased cardiac output and decreased peripheral vascular resistance and arterial pressure. Despite the baseline increase in cardiac output, cardiac function in patients with cirrhosis is abnormal in several respects. Patients show attenuated systolic and diastolic contractile responses to stress stimuli, electrophysiological repolarization changes, including prolonged QT interval, and enlargement or hypertrophy of cardiac chambers. This constellation of cardiac abnormalities is termed cirrhotic cardiomyopathy. It has been suggested that cirrhotic cardiomyopathy has a role in the pathogenesis of cardiac dysfunction and even overt heart failure after transjugular intrahepatic portosystemic shunt placement, major surgery and liver transplantation. Cardiac dysfunction contributes to morbidity and mortality after liver transplantation, even in many patients who have no prior history of cardiac disease. Depressed cardiac contractility contributes to the pathogenesis of hepatorenal syndrome, especially in patients with spontaneous bacterial peritonitis. Pathogenic mechanisms underlying cirrhotic cardiomyopathy include cardiomyocyte-membrane biophysical changes, attenuation of the stimulatory beta-adrenergic system and overactivity of negative inotropic systems mediated via cyclic GMP. The clinical features, general diagnostic criteria, pathogenesis and treatment of cirrhotic cardiomyopathy are discussed in this review.

Topics: Cardiovascular Agents; Heart Diseases; Humans; Liver Cirrhosis; Liver Transplantation; Portasystemic Shunt, Transjugular Intrahepatic; Treatment Outcome

In women, breast cancer is the second most common form of cancer and the leading cause of death caused by malignancy. The anthracycline antibiotics are potent anti-tumor agents used in a wide spectrum of malignancies. They are part of the gold standard adjuvant therapy for breast cancer and in metastatic disease they provide significant increases in response rate, time to disease progression, and overall survival. The addition of trastuzumab augments the effects of anthracycline-based therapy in both the adjuvant and metastatic settings. The successful use of anthracyclines is, however, restricted by the risk of developing life-threatening congestive heart failure. This risk increases exponentially with cumulative dose, and is further augmented by the addition of trastuzumab. Studies have reported that 10% to 26% of patients administered cumulative anthracycline doses above those recommended (> or =500 mg/m2 for doxorubicin and 1,000 mg/m2 for epirubicin) develop congestive heart failure, and that more than 50% of patients administered these doses will experience measurable functional impairment months to years after the end of therapy. The susceptibility of patients to anthracycline-induced cardiotoxicity varies widely, with a dramatic increase with advancing age. The onset of clinical and subclinical cardiac damage is delayed and occurs more than 3 months after the cessation of treatment, indicating a crucial time for functional impairment to occur and highlighting the ineffectiveness of monitoring left ventricular ejection fraction as an endpoint during anthracycline therapy. Possible future treatment options for managing anthracycline-induced cardiotoxicity include agents such as dexrazoxane that prevent oxygen-free radical generation. Further investigation is required into the use of angiotensin-converting enzyme inhibitors to redress cardiac damage and new methods of identifying patients at high risk of congestive heart failure before cardiac damage has occurred.

Topics: Age Factors; Anthracyclines; Antineoplastic Agents; Breast Neoplasms; Cardiovascular Agents; Disease Susceptibility; Female; Free Radical Scavengers; Heart; Heart Diseases; Heart Failure; Humans; Remission Induction; Risk Factors; Survival Rate

Despite significant advances in the detection, prevention and treatment of congestive heart failure, it remains a leading cause of morbidity and mortality. Recent research has revealed the potential role of stem and progenitor cells in repairing and regenerating damaged myocardium. A number of pharmacological agents that mobilize these cells, including granulocyte-colony stimulating factor, statins and AMD-3100, are currently under investigation. This review summarizes the rationale behind using these agents, as well as describing the preclinical and clinical data supporting their efficacy.

Topics: Animals; Benzylamines; Cardiovascular Agents; Cyclams; Endothelial Cells; Heart Diseases; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells; Heterocyclic Compounds; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Receptors, CXCR4; Receptors, Granulocyte Colony-Stimulating Factor; Regeneration

Pregnancy and delivery are associated with substantial physiological changes that require adaptations in the cardiovascular system. These changes, well-tolerated in pregnant women without heart disease, expose woman with cardiovascular disease to serious risk. In fact, heart disease is the most frequent cause of maternal death, after psychiatric disorders, and the number of pregnant women with heart disease is expected to grow in the coming years. Preventing cardiovascular complications should be the main aim of every cardiologist involved in managing pregnant woman with congenital or acquired heart disease. Unfortunately, there is a lack of data which would help in the management of these patients during pregnancy and the clinical practice guidelines are often based on assumptions regarding how a specific substrate is going to respond to the physiological changes occurring due to pregnancy.

Topics: Cardiovascular Agents; Female; Heart Diseases; Heart Function Tests; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Risk Factors

Topics: Biomarkers; Cardiovascular Agents; Crataegus; Evidence-Based Medicine; Heart Diseases; Heart Function Tests; Humans; Plant Extracts; Stroke Volume

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Echocardiography; Heart Diseases; Humans; Natriuretic Peptide, Brain; Stem Cell Transplantation; Tomography, X-Ray Computed

Topics: Animals; Cardiovascular Agents; Diabetic Angiopathies; Heart Diseases; Humans; Hypoglycemic Agents; Ischemic Preconditioning, Myocardial; Life Style

Recent studies call into question the necessity of hypertrophic growth of the heart as a "compensatory" response to hemodynamic stress. These findings, coupled with recent progress in dissecting the molecular bases of hypertrophy, raise the prospect of suppressing hypertrophy without provoking circulatory insufficiency. In this article, we focus on signaling pathways that hold promise as potential targets for therapeutic intervention. We also summarize observations from animal models and clinical trials that suggest benefit from an antihypertrophic strategy.

Topics: Adaptation, Physiological; Animals; Arrhythmias, Cardiac; Calcium; Cardiac Output; Cardiovascular Agents; Cell Size; Clinical Trials as Topic; Heart Diseases; Heart Failure; Humans; Hypertrophy, Left Ventricular; Ion Channels; Mechanoreceptors; Muscle Proteins; Myocytes, Cardiac; Pressure; Ventricular Remodeling

This article reviews the complications, management and prognosis of cardiac disease in pregnancy.

Topics: Antibiotic Prophylaxis; Cardiovascular Agents; Female; Heart Diseases; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Care

Pregnancy causes important alterations in the cardiovascular haemodynamics which have important bearing in the case of pre-existing cardiac disease. In addition, cardiovascular medications may be contraindicated in pregnant women. With a better recognition of the specific interactions between pregnancy and cardiac conditions, it is now possible to allow pregnancies in numerous women with recognised cardiac diseases.

Topics: Cardiovascular Agents; Female; Heart Diseases; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Risk Factors

Arterial stiffness is the most important cause of increasing systolic and pulse pressure, and for decreasing diastolic pressure with ageing. Many measures can be applied to quantify arterial stiffness, but all are approximations only, on account of the nonhomogenous structure of the arterial wall, its variability in different locations, at different levels of distending pressure, and with changes in smooth muscle tone. This article summarizes those indices with a focus on newer non-invasive methods and provides an overview of physiological, pathological and pharmacological influences on arterial hemodynamics. In the near future, the ability to detect and monitor subclinical arterial damage will improve cardiovascular risk stratification and act as a better guide in assessing the efficacy of therapeutic interventions than monitoring blood pressure alone. However, large-scale clinical trials are needed to prove the hypothesis that treatment of these new therapeutic targets will translate into clinical benefit, expressed in cardiovascular events or even mortality.

Topics: Age Factors; Arteries; Arteriosclerosis; Blood Flow Velocity; Cardiovascular Agents; Diabetes Complications; Exercise; Gender Identity; Heart Diseases; Hemodynamics; Humans; Hypertension; Pulsatile Flow

Reviewing advances in cardiology and haematology together may appear at first sight to require some artificiality to make a satisfying fit. For two reasons, at least, this is not the case. Firstly, convergence in biology has become very clear over the past decade and this could not be better illustrated by the demonstration that the haemangioblast is the common progenitor of both haemapoietic stem cells and vascular endothelium. This opens the way to common (and differential) approaches to the manipulation of these cells, a field at present in its infancy. A second convergence is the common goal of understanding the processes resulting in haemostasis, thrombosis and vascular occlusion and the means for developing effective antithrombotics. This is exemplified by a number of agents either in use or in clinical trial as a result of haematological and cardiological collaboration. This collaboration is recognisable with the development, many years ago, of streptokinase and the use of aspirin in vascular disease and continues to this day with specific antiplatelet inhibitors and oral thrombin inhibitors as they become accepted into clinical use over the next few years. Here we review current advances in pharmacological treatments in cardiology and haematology, grouped primarily by disease process, focusing on novel and emerging therapies likely to be of importance in the future.

Topics: Angioplasty, Balloon, Coronary; Animals; Cardiovascular Agents; Coronary Disease; Heart Diseases; Hematologic Diseases; Hematologic Neoplasms; Humans; Myocardial Infarction; Stem Cell Transplantation; Thrombosis

to summarize existing evidence regarding the benefits and the risks of all available interventional and medical means aimed at cardiac risk reduction in patients undergoing vascular surgery.. review of the literature.. a critical review of all studies examining the impact of various prophylactic cardiac maneuvers on perioperative outcome following vascular surgery was performed. Overall mortality, cardiac mortality and myocardial infarction rate were used as the outcome measures.. coronary artery bypass grafting is associated with a 60% decrease in perioperative mortality in patients undergoing vascular surgery, but in most of the cases this decrease does not outweigh the combined risk of the cardiac and the subsequent noncardiac vascular procedure. Data supporting the cardioprotective effect of percutaneous transluminal angioplasty in the perioperative setting are insufficient. beta-blockade has been shown to decrease perioperative mortality and cardiac morbidity in both high-risk (strong evidence) and low-risk (weak evidence) patients.. coronary revascularization is rarely indicated to simply get the patient through vascular surgery and should be reserved for patients who would need it irrespective of the scheduled vascular procedure. Among all available pharmacological agents, including beta-blockers, alpha-agonists, calcium channel blockers and nitrates, only beta-blockers have been proven to reduce the cardiac risk of vascular surgery.

Topics: Cardiac Surgical Procedures; Cardiovascular Agents; Evidence-Based Medicine; Heart Diseases; Humans; Risk Factors; Risk Reduction Behavior; Vascular Surgical Procedures

Cardiac toxicity due to anti-neoplastic agents has been recognized since doxorubicin, one of the most effective anthracyclines, was introduced in the early 1970s. Although the frequency of cardiac toxicity is relatively low compared with hematological and gastrointestinal toxicity, management of cardiac toxicity is crucial because of the possibility of irreversible cardiac damage. Recently, high dose-intense chemotherapy with G-CSF and stem cell transplantation, and mediastinal irradiation, produce even more toxic effects on the heart. This review describes some of the cardiac toxicity of anthracyclines and trastuzumab, and discusses attempts at management. The mainstay of management of cardiac toxicity is serial, adequate monitoring of cardiac functions.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cardiovascular Agents; Dose-Response Relationship, Drug; Doxorubicin; Echocardiography; Heart; Heart Diseases; Humans; Monitoring, Physiologic; Neoplasms; Razoxane

Topics: Cardiovascular Agents; Cardiovascular System; Drug Interactions; Heart Diseases; Humans; Mental Disorders; Psychotropic Drugs; Treatment Outcome

Topics: Cardiovascular Agents; Coitus; Counseling; Erectile Dysfunction; Heart; Heart Diseases; Heart Rate; Humans; Male; Phosphodiesterase Inhibitors; Physician's Role; Piperazines; Purines; Sexual Behavior; Sildenafil Citrate; Sulfones

Topics: Cardiovascular Agents; Dentistry; Endocarditis, Bacterial; Heart Diseases; Humans; Hypertension; Mouth Diseases; Oral Hygiene

Topics: Cardiology; Cardiovascular Agents; Counterpulsation; Heart Diseases; Heart Transplantation; Humans; Magnetic Resonance Angiography

The pregnant state imposes a supraphysiologic strain on the pregnant woman's cardiac performance through complex biochemical, electric, and physiologic changes affecting the blood volume, myocardial contractility, and resistance of the vascular bed. In the presence of underlying heart disease, these changes can compromise the woman's hemodynamic balance, her life, and that of her unborn child. Cardiac pathology represents a heterogeneous group of disorders, each with its own hemodynamic, genetic, obstetric, and social implications. Physicians caring for these women should actively address the issue of reproduction. Ideally, pregnancy should be planned to occur after optimization of cardiac performance by medical or surgical means. Once pregnancy is achieved, the concerted effort of a multidisciplinary team of obstetricians, cardiologists, anesthesiologists, nursing, social, and other services provides the best opportunity to carry the pregnancy to a successful outcome.

Topics: Algorithms; Cardiovascular Agents; Cardiovascular Physiological Phenomena; Delivery, Obstetric; Female; Heart Diseases; Humans; Postnatal Care; Preconception Care; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Care; Risk

Topics: Angina Pectoris; Cardiovascular Agents; Free Radical Scavengers; Heart Diseases; Humans; Myocardial Infarction; Nitric Oxide; Nitric Oxide Donors

The normal myocardium is composed of a variety of cells. Cardiac myocytes, tethered within an extracellular matrix of fibrillar collagen, represent one third of all cells; noncardiomyocytes account for the remaining two thirds. Ventricular hypertrophy involves myocyte growth. Hypertensive heart disease (HHD) includes myocyte and nonmyocyte growth that leads to an adverse structural remodeling of the intramural coronary vasculature and matrix. In HHD, it is not the quantity of myocardium but rather its quality that accounts for increased risk of adverse cardiovascular events. Structural homogeneity of cardiac tissue is governed by a balanced equilibrium existing between stimulator and inhibitor signals that regulate cell growth, apoptosis, phenotype, and matrix turnover. Stimulators (eg, angiotensin II, aldosterone, and endothelins) are normally counterbalanced by inhibitors (eg, bradykinin, NO, and prostaglandins) in a paradigm of reciprocal regulation. To reduce the risk of heart failure and sudden cardiac death that accompanies HHD, its adverse structural remodeling must be targeted for pharmacologic intervention. Cardioprotective agents counteract the imbalance between stimulators and inhibitors. They include ACE and endopeptidase inhibitors and respective receptor antagonists. Cardioreparative agents reverse the growth-promoting state and regress existing abnormalities in coronary vascular and matrix structure. ACE inhibition has achieved this outcome with favorable impact on vasomotor reactivity and tissue stiffness. Today's management of hypertension should not simply focus on a reduction in blood pressure, it must also target the adverse structural remodeling that begets HHD.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiovascular Agents; Endothelin Receptor Antagonists; Heart Diseases; Humans; Hypertension; Mineralocorticoid Receptor Antagonists; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2

Approximately 25,000 patients have been treated to date with the humanized anti-HER2 monoclonal antibody, Herceptin. This therapy has proved effective and well tolerated in patients with HER2-positive metastatic breast cancer; adverse events were generally infusion-related fever and chills of mild-to-moderate severity. Cardiotoxicity and infusion-related reactions emerged as the two main safety concerns with the use of Herceptin. Retrospective analysis revealed a higher incidence of heart failure when Herceptin was combined with anthracyclines than that expected with anthracyclines alone. Age, anthracycline exposure and cardiac risk factors were found to be predictors of cardiac adverse events. Patients experiencing cardiac dysfunction responded well to standard cardiac medication and the majority improved. Cardiac function should be monitored regularly and Herceptin should be discontinued if significant heart failure develops unless the benefits for an individual patient outweigh the risks. Of 25,000 patients, 74 (0.3%) were reported to have experienced a serious infusion-related reaction. The majority occurred during or shortly after the first infusion and were characterized by respiratory symptoms. Most patients were successfully treated; a total of 33 patients continued Herceptin therapy with no recurrence of infusion reactions. Although the benefit to risk ratio of Herceptin remains favorable, physicians must be vigilant and aggressive in managing cardiotoxicity and infusion-related reactions.

Topics: Animals; Antibiotics, Antineoplastic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiovascular Agents; Chills; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Interactions; Female; Fever; Heart Diseases; Heart Failure; Humans; Immunotherapy; Infusions, Intravenous; Neoplasm Metastasis; Pain; Palliative Care; Respiratory Insufficiency; Retrospective Studies; Risk Factors; Safety; Salvage Therapy; Trastuzumab; Treatment Outcome

Inflammation is a reaction to primary injury of various kinds, such as infection and trauma, which has both beneficial and detrimental effects. Inflammation has been associated with major diseases of the heart and vessels. Research has focused not only on ischaemia but also on post-ischaemic reperfusion, which is known to activate and amplify the inflammatory response. Although reperfusion should always be attempted in the clinical environment, it has been shown experimentally that it can cause some cardiac damage, in addition to that caused by ischaemia. Therefore, it is reasonable to attempt to increase the benefit obtainable with reperfusion by modulating inflammatory processes triggered by reperfusion itself. In this field, different potential therapeutic targets have been identified and interventions have been tested over the last 30 years. With the exception of adenosine, which probably does not act merely through inhibition of the inflammatory response, no other compounds have yet proven successful in clinical trials. Active research is ongoing. Broadening the approach from the heart to the cardiovascular system, promising data is emerging on cardiovascular protection conferred by statins in patients with coronary heart disease (CHD) and high levels of C-reactive protein (CRP), a systemic marker of inflammation. Similarly, results of trials aimed at preventing cardiovascular events by eradicating chronic infections will be among the first to directly test whether such therapies will decrease risks of cardiovascular disease.

Topics: Adenosine; Animals; Bacterial Infections; Cardiovascular Agents; Complement System Proteins; Cytokines; Enzyme Inhibitors; Heart Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Matrix Metalloproteinase Inhibitors; Neutrophils; Reactive Oxygen Species

Topics: Anesthesia; Anesthetics; Cardiovascular Agents; Drug Interactions; Heart Diseases; Heart Failure; Humans; Preoperative Care

Topics: Cardiovascular Agents; Chest Pain; Diagnosis, Differential; Heart Diseases; Humans; Physical Examination; Risk Assessment

Topics: Animals; Cardiovascular Agents; Heart Diseases; Humans; Pericardial Effusion; Pericardium

Topics: Acute Disease; Age Factors; Aged; Aged, 80 and over; Algorithms; Cardiac Surgical Procedures; Cardiovascular Agents; Cardiovascular Physiological Phenomena; Chronic Disease; Germany; Heart Diseases; Humans; Risk Factors

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Calcium Channel Blockers; Cardiotonic Agents; Cardiovascular Agents; Contraindications; Drug Interactions; Fibrinolytic Agents; Heart; Heart Diseases; Humans; Hydroxymethylglutaryl CoA Reductases; Liver; Vasodilator Agents

The provision of dental treatment under both local anaesthesia and sedation has an excellent safety record, although medical problems may occur. The high prevalence of cardiac disease in the population, particularly ischaemic heart disease, makes it the most common medical problem encountered in dental practice. Additionally, the increasing survival of children with congenital heart disease makes them a significant proportion of those attending for dental treatment. While most dental practitioners feel confident in performing cardio-pulmonary resuscitation, treating patients with co-existent cardio-vascular disease often causes concern over potential problems during treatment. This article aims to allay many of these fears by describing the commoner cardiac conditions and how they may affect dental treatment. It outlines prophylactic and remediable measures that may be taken to enable safe delivery of dental care.

Topics: Anesthesia, Dental; Angina Pectoris; Anticoagulants; Arrhythmias, Cardiac; Cardiovascular Agents; Dental Anxiety; Dental Care for Chronically Ill; Drug Interactions; Emergency Treatment; Endocarditis, Bacterial; Heart Defects, Congenital; Heart Diseases; Heart Valve Diseases; Humans; Hypertension; Monitoring, Intraoperative

Recent capability to enter the normal effusion-free pericardium has expanded intrapericardial therapy which was formerly restricted to patients with effusive pericardial disease, to intrapericardial treatment of cardiac diseases of all kinds. It is now possible to deposit in the intact pericardium a variety of therapeutic agents targeting the myocardium, valves, conduction system and even the endocardium. In addition to such specific agents, the unique microphysiology of the pericardial mesothelium provides investigators with 2 entirely new applications of intrapericardial therapy: 1. supplementing substances like prostanoids and a variety of immune factors, and 2. stimulating pericardial production of such products of metabolism, e.g., superfusion of the normal pericardium by non-steroidal antiinflammatory agents to stimulate prostanoid production with a variety of effects including possible inhibition of coronary thrombosis. Continuing research and development should determine the precise roles of these new applications in human medicine.

Topics: Cardiovascular Agents; Epithelium; Heart Diseases; Hemodynamics; Humans; Pericardium

Biological and mechanical stressors such as ischemia, hypoxia, cellular ATP depletion, Ca2+ overload, free radicals, pressure and volume overload, catecholamines, cytokines, and renin-angiotensin may independently cause reversible and/or irreversible cardiac dysfunction. As a defense against these forms of stress, several endogenous self-protective mechanisms are exerted to avoid cellular injury. Adenosine, a degradative substance of ATP, may act as an endogenous cardioprotective substance in pathophysiological conditions of the heart, such as myocardial ischemia and chronic heart failure. For example, when brief periods of myocardial ischemia precede sustained ischemia, infarct size is markedly limited, a phenomenon known as ischemic preconditioning. We found that ischemic preconditioning activates the enzyme responsible for adenosine release, ie, ecto-5'-nucleotidase. Furthermore, the inhibitor of ecto-5'-nucleotidase reduced the infarct size-limiting effect of ischemic preconditioning, which establishes the cause-effect relationship between activation of ecto-5'-nucleotidase and the infarct size-limiting effect. We also found that protein kinase C is responsible for the activation of ecto-5'-nucleotidase. Protein kinase C phosphorylated the serine and threonine residues of ecto-5'-nucleotidase. Therefore, we suggest that adenosine produced via ecto-5'-nucleotidase gives cardioprotection against ischemia and reperfusion injury. Also, we found that plasma adenosine levels are increased in patients with chronic heart failure. Ecto-5'-nucleotidase activity increased in the blood and the myocardium in patients with chronic heart failure, which may explain the increases in adenosine levels in the plasma and the myocardium. In addition, we found that further elevation of plasma adenosine levels due to either dipyridamole or dilazep reduces the severity of chronic heart failure. Thus, we suggest that endogenous adenosine is also beneficial in chronic heart failure. We propose potential mechanisms for cardioprotection attributable to adenosine in pathophysiological states in heart diseases. The establishment of adenosine therapy may be useful for the treatment of either ischemic heart diseases or chronic heart failure.

Topics: 5'-Nucleotidase; Adenosine; Adenosine Triphosphate; Cardiovascular Agents; Heart Diseases; Humans; Protein Kinase C

Modern cardiac rehabilitation is a comprehensive program of secondary prevention for patients with heart disease. Moreover, it is an important context in which to broach issues of impaired sexual function. Sexual problems plague a large portion of our cardiac patient population. Unspoken+ concerns about impotence, now more correctly called erectile dysfunction (ED), are common, as are concerns about the safety of engaging in sexual activity, especially after major cardiac events or therapeutic interventions. A large proportion of patients do not return to normal sexual activity after a cardiac event. Many factors, including normal age-related changes in sexual response, medication-induced dysfunction, and vascular changes associated with risk factors (e.g., diabetes and dyslipidemia), as well as the emotional impact of symptomatic heart disease, may influence sexual function in these patients. These factors, occurring alone or in combination, probably explain the discouraging prevalence of sexual dysfunction in patients with manifest cardiac disease. Because so few patients have specific cardiac reasons for limiting sexual activity, a clear opportunity exists for cardiologists and their staff to help enhance the emotional well-being and overall quality of life of their cardiac patients.

Topics: Aged; Aging; Attitude to Health; Cardiovascular Agents; Erectile Dysfunction; Female; Heart Diseases; Humans; Male; Quality of Life; Risk Factors; Sexual Behavior; Sexual Dysfunction, Physiological

To review the features of randomized clinical trials (RCTs) used in the development of agents that may protect against chemotherapy-induced toxicities, including trials of the cardioprotective agent dexrazoxane, hematologic growth factors, and amifostine; to suggest recommendations based on information gained from such trials and improvements in the design of ongoing and future trials.. Critical review of reports of RCTs obtained from a Medline search, references from these articles, and review of trials listed in the physician data query (PDQ) clinical trials data base.. Several of the phase III trials did not use a format of comparing widely accepted strategies of chemotherapy with and without a protective agent. Instead, patients in the control arms of some of the trials have been exposed to more prolonged use or increased dosage of toxic chemotherapy that placed them at greater risk of the toxicity the protective agent was designed to prevent (eg, cardiotoxicity in trials of dexrazoxane, myelosuppression or thrombocytopenia in trials of growth factors).. RCTs have shown clear evidence of biologic activity for the protective agents, but this does not imply therapeutic benefit as compared with alternative strategies such as avoidance of prolonged use of cardiotoxic agents or use of standard doses of chemotherapy. Ongoing and future trials of protective agents should be modified to avoid undue risk to patients.

Topics: Amifostine; Antineoplastic Agents; Cardiovascular Agents; Clinical Trials, Phase III as Topic; Heart Diseases; Hematopoietic Cell Growth Factors; Humans; Leukopoiesis; Randomized Controlled Trials as Topic; Razoxane; Research Design; Thrombocytopenia

Dexrazoxane prevents the dose-limiting cardiotoxicity of the anthracyclines without reducing their antitumor efficacy and without new adverse side effects. Dexrazoxane reduces the severity of gastrointestinal symptoms of the anthracycline containing combination doxorubicin, 5-fluorouracil, cyclophosphamide and most surprisingly and importantly, dexrazoxane increases the median survival time of advanced breast cancer responders to the doxorubicin, 5-fluorouracil, cyclophosphamide regimen. The median survival time is doubled as compared to controls to nearly 3 years.

Topics: Adult; Anthracyclines; Antineoplastic Agents; Breast Neoplasms; Cardiovascular Agents; Child; Clinical Trials as Topic; Heart Diseases; Humans; Razoxane

Two large multicenter placebo controlled trials (088001 and 088006) in metastatic breast cancer found a significant cardioprotective effect of dexrazoxane when administered with doxorubicin. A delayed dose analysis found a protective effect even after a cumulative dose of doxorubicin of 300 mg/m2. Exploratory analysis combing the arms on the two studies found a cardioprotective effect of dexrazoxane either initially or after 300 mg/m2 when administered in patients older than 65 years, compared to patients receiving only placebo. Also, patients with an ejection fraction within 10% above the lower limit of normal were protected with dexrazoxane. Objective response rates were borderline significantly lower for patients receiving dexrazoxane. Recommendations are to administer dexrazoxane after 300 mg/m2.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiovascular Agents; Dose-Response Relationship, Drug; Doxorubicin; Female; Heart Diseases; Humans; Multicenter Studies as Topic; Neoplasm Metastasis; Randomized Controlled Trials as Topic; Razoxane

The ability of dexrazoxane (DEX) to protect against anthracycline-induced cardiotoxicity has been evaluated in several European studies using either standard or high-dose regimens. In addition, one randomized trial investigated the value of cardiac radioimmunoscintigraphy with indium-111 antimyosin monoclonal antibodies in the early detection of cardiac damage. The results of these trials demonstrate that DEX is able to ameliorate doxorubicin- and epirubicin-induced cardiotoxicity, even when high single drug doses are used. The cardioprotective effect of DEX has been clearly documented by both clinical and laboratory cardiac evaluation. The use of DEX did not add to the toxicity of the anthracyclines, nor was there clear evidence of an adverse impact of the agent on antitumor activity of the chemotherapeutic regimen. Radioimmunoscintigraphy was very sensitive in detecting anthracycline cardiac damage, but its specificity is low and it cannot be considered a primary test for guiding anthracycline treatment.

Topics: Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cardiovascular Agents; Clinical Trials as Topic; Doxorubicin; Epirubicin; Europe; Heart Diseases; Humans; Razoxane

Anthracyclines have major activity against a broad range of childhood cancers. Concern over the risk of long-term cardiotoxicity associated with their use has called into question the role of these agents in the frontline treatment of many patients. Dexrazoxane was developed as a specific cardioprotectant "antidote" which can prevent anthracycline cardiotoxicity without inhibiting its antitumor effect. To date, four clinical trials of dexrazoxane have been conducted in pediatric cancer patients (primarily with sarcomas). The two largest series, conducted at the National Cancer Institute Pediatric Branch, demonstrated significant short-term cardioprotection with no evidence of interference with antitumor activity. Additional clinical trials are ongoing, or planned to open shortly, to better evaluate the role of dexrazoxane in the treatment of childhood cancer. These studies, being conducted on larger numbers of patients with better prospects for cure, are expected to definitviely answer the outstanding questions of whether preventing short-term, subclinical cardiotoxicity will translate into long-term cardioprotection, and whether the use of dexrazoxane interferes with the anti-tumor efficacy of doxorubicin-containing regimens.

Topics: Anthracyclines; Antineoplastic Agents; Cardiovascular Agents; Child; Clinical Trials as Topic; Heart Diseases; Humans; Razoxane

Dexrazoxane has been used successfully to reduce cardiac toxicity in patients receiving anthracycline-based chemotherapy for cancer (predominantly women with advanced breast cancer). The drug is thought to reduce the cardiotoxic effects of anthracyclines by binding to free and bound iron, thereby reducing the formation of anthracycline-iron complexes and the subsequent generation of reactive oxygen species which are toxic to surrounding cardiac tissue. Clinical trials in women with advanced breast cancer have found that patients given dexrazoxane (about 30 minutes prior to anthracycline therapy; dexrazoxane to doxorubicin dosage ratio 20:1 or 10:1) have a significantly lower overall incidence of cardiac events than placebo recipients (14 or 15% vs 31%) when the drug is initiated at the same time as doxorubicin. Cardiac events included congestive heart failure (CHF), a significant reduction in left ventricular ejection fraction and/or a > or = 2-point increase in the Billingham biopsy score. These results are supported by the findings of studies which used control groups (patients who received only chemotherapy) for comparison. The drug appears to offer cardiac protection irrespective of pre-existing cardiac risk factors. In addition, cardiac protection has been shown in patients given the drug after receiving a cumulative doxorubicin dose > or = 300 mg/m2. It remains to be confirmed that dexrazoxane does not affect the antitumour activity of doxorubicin: although most studies found that clinical end-points (including tumour response rates, time to disease progression and survival duration) did not differ significantly between treatment groups, the largest study did show a significant reduction in response rates in dexrazoxane versus placebo recipients. Dexrazoxane permits the administration of doxorubicin beyond standard cumulative doses; however, it is unclear whether this will translate into prolonged survival. Preliminary results (from small nonblind studies) indicate that dexrazoxane reduces cardiac toxicity in children and adolescents receiving anthracycline-based therapy for a range of malignancies. The long term benefits with regard to prevention of late-onset cardiac toxicity remain unclear. With the exception of severe leucopenia [Eastern Cooperative Oncology Group (ECOG) grade 3/4 toxicity], the incidence of haematological and nonhaematological adverse events appears similar in patients given dexrazoxane to that in placebo recipients undergoing. Dexrazoxane is a valuable drug for protecting against cardiac toxicity in patients receiving anthracycline-based chemotherapy. Whether it offers protection against late-onset cardiac toxicity in patients who received anthracycline-based chemotherapy in childhood or adolescence remains to be determined. Further clinical experience is required to confirm that it does not adversely affect clinical outcome, that it is a cost-effective option, and to determine the optimal treatment regimen.

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Cardiovascular Agents; Chelating Agents; Heart Diseases; Humans; Neoplasms; Razoxane

Cardiotoxicity is the most important side effect of the highly effective chemotherapeutic drugs anthracyclines. The total dose that must not be surpassed to avoid cardiotoxicity is specific for each anthracycline. For doxorubicin the maximal dose is 450-550 mg/mq. Nevertheless cardiotoxicity can be observed in some cases even with doses smaller than the critical ones. Clinical signs of cardiotoxic damage can appear at any stage during the course of therapy. The prevention of cardiac damage can be tried in three ways. Firstly one should extend the administration period of the total dose of the drug for about 6 hours. The second way is based on the use of anthracycline analogs less toxic and possibly equally effective than doxorubicin. Finally one can associate to the anthracycline a cardioprotective drug such as ICRF187. The diagnosis of cardiotoxicity is usually reached evaluating the reduction of left ventricular ejection fraction either with echocardiography or with angiocardiography. Other parameters, particularly those evaluating the diastolic function, are under study to make the diagnosis more quick and accurate. Both cardiac scintigraphy and tomography also seem to offer promising tools for the diagnosis of anthracycline cardiotoxicity. Endomyocardiac biopsy is highly effective for the diagnosis, but is indicated only for selected cases. The therapy of anthracycline cardiomyopathy is directed mainly to the control of congestive heart failure. In the initial phase the treatment is based on the use of digitalis and diuretics, that are substituted in the following maintaining phase by ACE inhibitors.

Topics: Anthracyclines; Cardiovascular Agents; Heart; Heart Diseases; Humans; Razoxane

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

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

Topics: Antibiotics, Antineoplastic; Cardiovascular Agents; Heart Diseases; Humans; Razoxane

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Cardiovascular Agents; Clinical Trials as Topic; Combined Modality Therapy; Dose-Response Relationship, Drug; Doxorubicin; Female; Heart; Heart Diseases; Humans; Iron; Myocardium; Razoxane; Safety; Treatment Outcome

Topics: Antibiotics, Antineoplastic; Cardiovascular Agents; Heart; Heart Diseases; Humans; Razoxane

The main cardiovascular effect of aging is a rise of the systolic blood pressure due to reduced impedance of the central arteries. The resulting increase of the afterload leads to hypertrophy, increased rigidity and lengthening of the relaxation period in the left ventricle. The manifestations of ischaemia or arrhythmias are often atypical at more advanced ages and may delay diagnosis. Ejection murmur due to stenosis of the aortic valve, to calcification or degeneration, may be difficult to distinguish from a functional murmur. The cause of heart failure is usually coronary sclerosis and, less often, hypertension or a valvular defect. Systolic heart failure is associated with decreased contractility of the left ventricle and compensatory dilation, diastolic heart failure with reduced filling of the ventricles. Both forms respond well to acute treatment with antihypertensive, diuretic and (or) vasodilator drugs; the treatment in isolated diastolic heart failure should also focus on lowering the increased blood pressure and reducing the heart rate to increase the filling phase.

Topics: Aged; Aging; Cardiovascular Agents; Cardiovascular Physiological Phenomena; Heart Diseases; Heart Failure; Heart Valve Diseases; Hemodynamics; Humans

Chemotherapy drugs have been reported to cause cardiac side effects including cardiomyopathy, ischemia, arrhythmias, and myocardial necrosis. Most important in terms of daily practice is anthracycline-induced cardiomyopathy. The bisdioxopiperazine compound, dexrazoxane (ICRF-187, ADR-529), has been shown to prevent this cumulative side effect of the anthracyclines. Recent randomized trials performed in breast cancer and in pediatric sarcoma patients have demonstrated the efficacy of this approach, which permits the administration of anthracyclines to greater cumulative doses and thus leads to a substantial reduction in the incidence of decreased left-ventricular ejection fraction or congestive heart failure. Response rates were not significantly different with the use of dexrazoxane in these trials. The risk ratio for a cardiac event was decreased by two to threefold in randomized breast studies involving more than 700 women. Paclitaxel also has been reported to cause arrhythmias and possibly ischemia. In a large data base, National Cancer Institute investigators found a 0.29% incidence of grade 4 or 5 cardiac toxicities, including heart block, ventricular tachycardia, and ischemic events. Other important chemotherapy-related cardiac toxicities discussed include fluorouracil-induced angina and arrhythmias, interleukin-4 induced-cardiomyopathy, and cardiotoxicity associated with autologous bone marrow transplantation procedures.

Topics: Adult; Anthracyclines; Antineoplastic Agents; Cardiovascular Agents; Child; Clinical Trials as Topic; Cyclophosphamide; Female; Fluorouracil; Heart; Heart Diseases; Humans; Interleukin-2; Male; Neoplasms; Paclitaxel; Razoxane; Retrospective Studies; Survivors

Pregnancy is associated with major hemodynamic changes in the cardiovascular system that can contribute to greater morbidity and mortality in women with underlying heart disease. Therefore, the diagnosis and management of these disorders in the pregnant patient require understanding of cardiovascular physiology during pregnancy, labor, delivery, and the puerperium. It is also essential to have knowledge about safety and utility of various diagnostic modalities and drugs during pregnancy to treat maternal heart disease without compromising fetal well-being.

Topics: Cardiovascular Agents; Female; Heart Defects, Congenital; Heart Diseases; Heart Function Tests; Heart Transplantation; Heart Valve Prosthesis; Humans; Pregnancy; Pregnancy Complications, Cardiovascular

Cardiovascular diseases remain the leading cause of death in ESRF patients. Coronary risk factors such as hypertension and lipid abnormalities are prevalent in the dialysis population and may be difficult to control. Special factors contributing to the imbalance between myocardial oxygen supply and demand include anemia, arteriovenous fistula, and the hemodialysis procedure itself. LVH and left ventricular dilation frequently result in symptomatic CHF. Atrial and ventricular arrhythmias are common; pericarditis may also occur. Control of the extracellular fluid volume through ultrafiltration with dialysis and the dietary avoidance of salt and water is critical to controlling hypertension in the dialysis population. The potential for drug side effects and the altered pharmacokinetics of medications in renal failure patients should be considered when prescribing cardiovascular drugs.

Topics: Cardiovascular Agents; Heart Diseases; Humans; Hypertension, Renal; Hypotension; Kidney Failure, Chronic; Renal Dialysis; Risk Factors

Topics: Animals; Calcium Channel Agonists; Cardiac Glycosides; Cardiovascular Agents; Catecholamines; Cyclic AMP; Heart Diseases; Heart Failure; Hemodynamics; Humans; Phosphodiesterase Inhibitors; Quinolines; Sodium Channels; Vasodilator Agents

To review clinical research pertaining to continuous ambulatory peritoneal dialysis (CAPD) and the heart.. A Medline computer search was employed to identify appropriate references from 1970 - 1994. Indexing terms were: continuous ambulatory peritoneal dialysis, hemodialysis, heart or cardiac, left ventricle, coronary artery disease, and survival. English and non-English language abstracts were scrutinized.. Forty-six studies were reviewed and utilized. Numerical data extracted are reported in this review as they were reported in the original article.. This review provides a broad-based survey of studies pertaining to CAPD and the heart. Most of the studies relate to CAPD and left ventricular structure or function. Little information exists concerning CAPD and coronary artery disease, valvular disease, pericardial disease, and cardiac arrhythmias. Studies pertaining to patient survival on CAPD identify coronary artery disease and congestive heart failure as major risk factors, but in-depth quantification of these cardiovascular disorders is lacking in the literature.. CAPD is capable of decreasing left ventricular (LV) volume and improving LV systolic function in patients with LV enlargement and those with LV systolic dysfunction. The effect of CAPD on left ventricular hypertrophy (LVH) and LV diastolic function is variable. CAPD produces symptomatic improvement in patients with refractory congestive heart failure, but its effect on survival in such patients is uncertain. Atherogenic lipid abnormalities occur in CAPD patients. The clinical significance of these abnormalities is uncertain. Coronary artery bypass surgery can be performed safely and effectively on CAPD patients. CAPD is not arrhythmogenic. Survival of CAPD patients is similar to that of hemodialysis patients except in elderly diabetics for whom it is slightly lower.

Topics: Arrhythmias, Cardiac; Cardiac Surgical Procedures; Cardiovascular Agents; Coronary Disease; Heart Diseases; Humans; Kidney Failure, Chronic; Peritoneal Dialysis, Continuous Ambulatory; Ventricular Function, Left

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Heart Diseases; Humans

Topics: Cardiovascular Agents; Heart Diseases; Humans; Lung Diseases

With rapidly progressing therapeutic methods in the cardiovascular medicine, scientific evaluations for newly developed cardiovascular drugs and therapies have become mandatory. We have launched five large scale multicenter cooperative studies, namely, Japan Multicenter Investigation for Cardiovascular Drugs/Therapies, J-MIC (I), (B), (M), (S), and (K). The aims of studies include to investigate: the best therapeutic approach in patients with acute myocardial infarction who underwent thrombolytic therapy with or without any adjunctive treatment (I), the long-term comparative study (3 years) of nifedipine (extended release tablet) with ACE inhibitor in patients with essential hypertension and ischemic heart disease (B), the long-term effect (3 years) of trapidil and/or ethyl icosapentate in patients with ischemic heart disease with or without arteriosclerotic obstructive disease in terms of progression or regression of atherosclerotic changes in coronary as well as peripheral arteries (M), the efficacy and safety of pravastatin to prevent post-PTCA restenosis (S), and regression of atherosclerotic lesion of coronary arteries in patients with familial hypercholesterolemia by LDL apheresis (K).

Topics: Cardiovascular Agents; Clinical Protocols; Coronary Artery Disease; Coronary Disease; Female; Heart Diseases; Humans; Hypertension; Japan; Male; Multicenter Studies as Topic

The developmental aspects of myocardial performance must be considered when pharmacologic agents are used to support the neonate with compromised cardiac function. Neonatal cardiovascular function is characterized by a limited preload reserve, decreased ventricular compliance, limited contractile reserve, and CO that is primarily dependent on the HR. Nurses caring for these neonates need a baseline understanding of normal cardiovascular physiology to evaluate the effectiveness of pharmacologic interventions to augment CO. Neonatal nurses play a pivotal role in the therapeutic management of pharmacologic interventions to provide safe, high quality care for the sick neonate.

Topics: Cardiovascular Agents; Child Development; Child, Preschool; Heart Diseases; Hemodynamics; Humans; Infant, Newborn

To review the available information about nitrate tolerance, its potential mechanisms, clinical implications, and strategies for prevention.. A survey of the National Library of Medicine MEDLINE database and bibliographies of the reviewed articles.. Studies were selected from the English language literature with an emphasis on recent studies and, when available, randomized placebo-controlled studies. Old studies were selected on the basis of their historical value and originality. A total of 134 retrieved articles were considered relevant and were reviewed in depth.. The available information about the experimental as well as the clinical evidence for tolerance to organic nitrates has been summarized. In addition, information related to potential mechanisms, clinical implications, and possible methods for prevention have been reviewed.. Evidence indicates that prolonged in-vitro exposure to organic nitrates, continuous intravenous or topical administration of nitrates, and frequent in-vivo oral dosing result in the rapid development of tolerance to the peripheral as well as to the coronary vasodilatory effects of the drugs. This phenomenon leads to the rapid attenuation of the hemodynamic and anti-ischemic effects of nitrates in patients with ischemic heart disease or congestive heart failure, or both. Tolerance development seems to be dose- and time-dependent, and its main mechanism seems to be a depletion of sulfhydryl groups at the vascular cell. Although the repletion of sulfhydryl groups with the use of sulfhydryl-containing drugs may help to prevent tolerance, the efficacy and safety of this approach requires further evaluation. Intermittent therapy allowing a sufficiently long, daily nitrate-washout interval seems to be the most effective and the most safe strategy currently available for the prevention of nitrate tolerance.

Topics: Cardiovascular Agents; Drug Tolerance; Heart Diseases; Hemodynamics; Humans; Nitrates

Dietary magnesium (Mg) deficiency is more prevalent than generally suspected and can cause cardiovascular lesions leading to disease at all stages of life. The average American diet is deficient in Mg, especially in the young, in alcoholic persons, and in those under stress or with diseases or receiving certain drug therapies, who have increased Mg needs. Otherwise normal, Mg-deficient diets cause arterial and myocardial lesions in all animals studied, and diets that are atherogenic, thrombogenic and cardiovasopathic, as well as Mg-deficient, intensify the cardiovascular lesions, whereas Mg supplementation prevents them. Diuretics and digitalis can intensify an underlying Mg deficiency, leading to cardiac arrhythmias that are refractory unless Mg is added to the regimen. Potassium (K) depletion in diuretic-treated hypertensive patients has been linked to an increased incidence of ventricular ectopy and sudden death. K supplementation alone is not the answer. Mg has been found to be necessary to intracellular K repletion in these patients. Because patients with congestive heart failure and others receiving diuretic therapy are also prone to chloride loss leading to metabolic alkalosis that also interferes with K repletion, the addition of Mg and chloride supplements in addition to the K seems prudent.

Topics: Cardiovascular Agents; Cardiovascular Diseases; Chlorides; Diet; Female; Heart Diseases; Humans; Hypertension; Magnesium; Magnesium Deficiency; Potassium; Pregnancy; Stress, Physiological

Disorders of the heart frequently cause pulmonary dysfunction because of the close structural and functional association of the heart and lungs. The pulmonary vasculature is very commonly affected by cardiac pathology. The pulmonary vasculature is normally a low-pressure, low-resistance circuit with high compliance and tremendous vascular reserve. Although resting vascular tone is low, there are many identified mediators of pulmonary arterial tone that may help mediate pulmonary blood flow. Alveolar hypoxia is clearly a stimulus for increasing pulmonary vascular resistance although factors that mediate the response to hypoxia are not fully understood. Patients with left-to-right shunting due to congenital heart disease because of elevations in pulmonary artery flow and pressure tend to develop progressive anatomic changes in the pulmonary vasculature. This leads to an increase in pulmonary vascular resistance, irreversible pulmonary hypertension, right heart failure, reversal of shunt flow, and Eisenmenger's syndrome. The degree of anatomic vascular damage due to left-to-right shunting can be graded histologically. Lesser grades of damage are reversible with corrective surgery, whereas more severe grades show no improvement or progression with operation. Chronic left-sided congestive heart failure seen in rheumatic mitral stenosis can cause secondary changes in the pulmonary vasculature. Pulmonary hypertension and increased pulmonary vascular resistance can increase reflexly and form a "second stenosis" that further limits cardiac output. Unlike congenital heart disease, severe grades of pulmonary arterial damage are not seen in left heart failure from mitral stenosis or other causes, and consequently with surgical correction pulmonary hypertension reverses. Pulmonary function testing is adversely affected by congestive heart failure. Both restrictive (stiff lungs) and obstructive (cardiac asthma) defects are observed in congestive heart failure. DLCO is abnormally decreased. With treatment of heart failure these defects reverse. Both elevated systemic and pulmonary venous pressures affect fluid filtration in the pleural space and cause pleural fluid accumulation. The fluid is transudative with low protein, low lactate dehydrogenase, and low cell counts. Transudative effusions from heart failure resolve with treatment. With large effusions and cardiomegaly, pulmonary dysfunction results because of atelectasis from compression and space-occupying effects o

Topics: Cardiovascular Agents; Heart Defects, Congenital; Heart Diseases; Humans; Hypertension, Pulmonary; Lung Diseases; Pleural Diseases; Pulmonary Circulation; Pulmonary Embolism; Respiratory Function Tests

Topics: Antidepressive Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Depressive Disorder; Heart Diseases; Humans; Monoamine Oxidase Inhibitors; Prospective Studies; Risk Factors

Reduced drug metabolism, both renal and hepatic, occurs with aging. Algorithms for dose adjustments of renally excreted drugs are available, but dose adjustments must be empiric for drugs which undergo hepatic metabolism. Decreased drug clearance in combination with potentially increased sensitivity to drugs in the elderly means that, as a general rule, drug dosages should be reduced as the age of the patient increases. The frequent need for multi-drug therapy may also lead to adverse effects in the elderly compared with younger cardiac patients. Managing the geriatric patient requires careful drug monitoring and a heightened awareness of the potential for adverse drug effects.

Topics: Aged; Aging; Cardiovascular Agents; Female; Heart Diseases; Humans; Kinetics; Male

Topics: Blood Pressure; Cardiovascular Agents; Electrocardiography; Erectile Dysfunction; Female; Heart Diseases; Heart Rate; Humans; Male; Sex

Glucagon is an important therapeutic agent in critical care medicine. Although its endogenous hormonal functions have been well described, its clinical uses are rarely discussed. Glucagon is effective in the treatment of hypoglycemia, cardiogenic shock and heart failure, propranolol overdose, esophageal meat impaction, ureteral colic due to calculi, and acute diverticulitis. It may prove useful in the treatment of endotoxin and hypovolemic shock as well as toxicity due to excesses of procainamide, quinidine, or ouabain.

Topics: Cardiotonic Agents; Cardiovascular Agents; Colic; Diverticulitis; Esophagus; Glucagon; Heart Diseases; Heart Rate; Humans; Hypoglycemia; Muscle, Smooth; Myocardial Contraction; Peristalsis; Ureteral Calculi

Topics: Aged; Antidepressive Agents, Tricyclic; Cardiovascular Agents; Cardiovascular Diseases; Heart Diseases; Humans; Mental Disorders

Topics: Adrenergic beta-Antagonists; Analgesics, Opioid; Anti-Arrhythmia Agents; Atropine; Calcium Channel Blockers; Cardiotonic Agents; Cardiovascular Agents; Cardiovascular Diseases; Digitalis Glycosides; Emergency Medical Services; Heart Diseases; Heparin; Humans; Lidocaine; Nitroprusside; Oxygen Inhalation Therapy; Vasodilator Agents

Topics: Cardiovascular Agents; Delivery, Obstetric; Female; Fetus; Heart Diseases; Hemodynamics; Humans; Labor, Obstetric; Monitoring, Physiologic; Pregnancy; Pregnancy Complications, Cardiovascular

Topics: Antidepressive Agents, Tricyclic; Antipsychotic Agents; Cardiovascular Agents; Cardiovascular System; Contraceptives, Oral, Hormonal; Dose-Response Relationship, Drug; Female; Heart; Heart Diseases; Humans; Phenothiazines; Time Factors

Topics: Biological Availability; Cardiovascular Agents; Digoxin; Half-Life; Heart Diseases; Humans; Kinetics; Lidocaine; Models, Biological; Procainamide; Propranolol; Quinidine

The availability of specific, sensitive, and convenient analytic methods has simplified determinations of plasma concentrations of several cardioactive drugs. The available data indicate that, although in general the plasma concentrations of cardioactive drugs bear a more consistent relationship to their pharmacologic effects than the doses administered, they cannot substitute for careful clinical observation and judgment. Plasma concentrations of these drugs, following a given dose, are influenced by several factors which include patient's size, renal, hepatic, cardiac, and gastrointestinal function, bioavailability of the drug, and interplay with other concurrently administered drugs. These factors cannot be predicted with any degree of accuracy before starting therapy, but measuring plasma drug concentrations under appropriate conditions can be helpful in determining individual differences in drug disposition. The majority of patients can be treated without the use of plasma concentrations of digitalis and antiarrhythmic drugs. However, the availability of measurements can be helpful in a variety of specific clinical situations discussed in the text. In practice, plasma concentrations have been most valuable in the recognition of digitalis toxicity and as guides to therapy of resistant tachyarrhythmias requiring high dosages of single or multiple antiarrhythmic drugs.

Topics: Anti-Arrhythmia Agents; Cardiotonic Agents; Cardiovascular Agents; Dose-Response Relationship, Drug; Heart Diseases; Humans; Patient Compliance

Topics: Amyl Nitrite; Cardiovascular Agents; Coronary Disease; Digitalis Glycosides; Heart Diseases; Humans; Nitroglycerin; Pharmacology; Quinidine

Anthracyclines treat a broad range of cancers. Basic and retrospective clinical data have suggested that use of atorvastatin may be associated with a reduction in cardiac dysfunction due to anthracycline use.. To test whether atorvastatin is associated with a reduction in the proportion of patients with lymphoma receiving anthracyclines who develop cardiac dysfunction.. Double-blind randomized clinical trial conducted at 9 academic medical centers in the US and Canada among 300 patients with lymphoma who were scheduled to receive anthracycline-based chemotherapy. Enrollment occurred between January 25, 2017, and September 10, 2021, with final follow-up on October 10, 2022.. Participants were randomized to receive atorvastatin, 40 mg/d (n = 150), or placebo (n = 150) for 12 months.. The primary outcome was the proportion of participants with an absolute decline in left ventricular ejection fraction (LVEF) of ≥10% from prior to chemotherapy to a final value of <55% over 12 months. A secondary outcome was the proportion of participants with an absolute decline in LVEF of ≥5% from prior to chemotherapy to a final value of <55% over 12 months.. Of the 300 participants randomized (mean age, 50 [SD, 17] years; 142 women [47%]), 286 (95%) completed the trial. Among the entire cohort, the baseline mean LVEF was 63% (SD, 4.6%) and the follow-up LVEF was 58% (SD, 5.7%). Study drug adherence was noted in 91% of participants. At 12-month follow-up, 46 (15%) had a decline in LVEF of 10% or greater from prior to chemotherapy to a final value of less than 55%. The incidence of the primary end point was 9% (13/150) in the atorvastatin group and 22% (33/150) in the placebo group (P = .002). The odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost 3 times greater for participants randomized to placebo compared with those randomized to atorvastatin (odds ratio, 2.9; 95% CI, 1.4-6.4). Compared with placebo, atorvastatin also reduced the incidence of the secondary end point (13% vs 29%; P = .001). There were 13 adjudicated heart failure events (4%) over 24 months of follow-up. There was no difference in the rates of incident heart failure between study groups (3% with atorvastatin, 6% with placebo; P = .26). The number of serious related adverse events was low and similar between groups.. Among patients with lymphoma treated with anthracycline-based chemotherapy, atorvastatin reduced the incidence of cardiac dysfunction. This finding may support the use of atorvastatin in patients with lymphoma at high risk of cardiac dysfunction due to anthracycline use.. ClinicalTrials.gov Identifier: NCT02943590.

Topics: Adult; Aged; Anthracyclines; Antibiotics, Antineoplastic; Atorvastatin; Cardiovascular Agents; Double-Blind Method; Female; Follow-Up Studies; Heart Diseases; Heart Failure; Humans; Lymphoma; Male; Middle Aged; Retrospective Studies; Stroke Volume; Ventricular Function, Left

Cardiac rehabilitation (CR) is an essential component of contemporary management for patients with coronary heart disease, including following an acute coronary syndrome (ACS). CR typically involves education and support to assist people following an ACS to make lifestyle changes and prevent subsequent events. Despite its benefits, uptake and participation in tradition CR programs is low. The use of mobile technologies (mHealth) offers the potential to improve reach, access, and delivery of CR support. We aim to determine the effectiveness and cost-effectiveness of a text-messaging intervention (Text4Heart II) to improve adherence to medication and lifestyle change in addition to usual care in people following an ACS. A second aim is to use the RE-AIM framework to inform the potential implementation of Text4Heart II within health services in New Zealand.. Text4Heart II is a two-arm, parallel, superiority randomized controlled trial conducted in two large metropolitan hospitals in Auckland, New Zealand. Three hundred and thirty participants will be randomized to either a 24-week theory- and evidence-based personalized text message program to support self-management in addition to usual CR, or usual CR alone (control). Outcomes are assessed at 6 and 12 months. The primary outcome is the proportion of participants adhering to medication at 6 months as measured by dispensed records. Secondary outcomes include medication adherence at 12 months, the proportion of participants adhering to self-reported healthy behaviors (physical activity, fruit and vegetable consumption, moderating alcohol intake and smoking status) measured using a composite health behavior score, self-reported medication adherence, cardiovascular risk factors (lipids, blood pressure), readmissions and related hospital events at 6 and 12 months. A cost-effectiveness analysis will also be conducted. Using the RE-AIM framework, we will determine uptake and sustainability of the intervention.. The Text4Heart II trial will determine the effectiveness of a text-messaging intervention to improve adherence to medication and lifestyle behaviors at both 6 and 12 months. Using the RE-AIM framework this trial will provide much needed data and insight into the potential implementation of Text4Heart II. This trial addresses many limitations/criticisms of previous mHealth trials; it builds on our Text4Heart pilot trial, it is adequately powered, has sufficient duration to elicit behavior change, and the follow-up assessments (6 and 12 months) are long enough to determine the sustained effect of the intervention.. Australian New Zealand Clinical Trials Registry, ID: ACTRN12616000422426 . Registered retrospectively on 1 April 2016.

Topics: Cardiac Rehabilitation; Cardiovascular Agents; Cost-Benefit Analysis; Health Behavior; Health Care Costs; Heart Diseases; Humans; Medication Adherence; Multicenter Studies as Topic; New Zealand; Randomized Controlled Trials as Topic; Reminder Systems; Risk Reduction Behavior; Self Care; Text Messaging; Time Factors; Treatment Outcome

Anthracyclines (ANTs) are a class of active antineoplastic agents with topoisomerase-interacting activity that are considered the most active agents for the treatment of breast cancer. We investigated the efficacy of carvedilol in the inhibition of ANT-induced cardiotoxicity.. In this randomized, single-blind, placebo-controlled study, 91 women with recently diagnosed breast cancer undergoing ANT therapy were randomly assigned to groups treated with either carvedilol (n = 46) or placebo (n = 45). Echocardiography was performed before and at 6 months after randomization, and absolute changes in the mean left ventricular ejection fraction, left ventricular end diastolic volume, and left ventricular end systolic volume were determined. Furthermore, the percentage change in the left atrial (LA) diameter and other variables of left ventricular (LV) diastolic function, such as transmitral Doppler parameters, including early (E wave) and late (A wave) diastolic velocities, E/A ratio and E wave deceleration time, pulmonary venous Doppler signals, including forward systolic (S wave) and diastolic (D wave) velocities into LA, late diastolic atrial reversal velocity, and early diastolic tissue Doppler mitral annular velocity (e') were measured. In addition, tissue Doppler mitral annular systolic (s') velocity, as a marker of early stage of LV systolic dysfunction, E/e' ratio, as a determinant of LV filling pressure, and troponin I level, as a marker of myocardial necrosis were measured.. At the end of follow-up period, left ventricular ejection fraction did not change in the carvedilol group. However, this parameter was significantly reduced in the control group (P < 0.001). Echocardiography showed that both left ventricular end systolic volume and LA diameter were significantly increased compared with the baseline measures in the control group. In pulse Doppler studies, pulmonary venous peak atrial reversal flow velocity was significantly increased in the control group. Moreover, a significant decrease in the mitral annuli early diastolic (e') and peak systolic (s') velocities and a significant increase in the E (the peak early diastolic velocity)/e' ratio in the control group were also observed. However, none of these variables were adversely changed at the end of follow-up in the carvedilol group. Furthermore, the TnI level was significantly higher in the control group than in the carvedilol group (P = 0.036) at 30 days after the initiation of chemotherapy.. Prophylactic use of carvedilol may inhibit the development of anthracycline-induced cardiotoxicity, even at low doses.

Topics: Adult; Aged; Anthracyclines; Antibiotics, Antineoplastic; Atrial Function, Left; Biomarkers; Breast Neoplasms; Carbazoles; Cardiotoxicity; Cardiovascular Agents; Carvedilol; Echocardiography, Doppler, Pulsed; Female; Heart Diseases; Humans; Iran; Middle Aged; Propanolamines; Risk Assessment; Risk Factors; Single-Blind Method; Stroke Volume; Time Factors; Treatment Outcome; Troponin I; Ventricular Function, Left; Young Adult

The SYNTAX score (SXscore) has been shown to be an effective predictor of clinical outcomes in patients undergoing percutaneous coronary intervention (PCI).. The SXscore was prospectively collected in 1,397 of the 1,707 patients enrolled in the "all-comers" LEADERS trial (patients post-surgical revascularisation were excluded). Post hoc analysis was performed by stratifying clinical outcomes at two-year follow-up, according to one of three SXscore tertiles: SXlow ≤8 (n=464), 816 (n=461). At two-year follow-up the rate of major adverse cardiovascular events was 18.4%, 12.0% and 9.4% in the SXhigh, SXmid, and SXlow tertile, respectively (HR 1.45; CI 1.21-1.74; p<0.01). There was a significantly higher rate of cardiac death in patients in the highest SXscore tertile (7% SXhigh versus 2.4% SXmid versus 1.8% SXlow; HR 2.22; CI 1.5-3.27; p<0.001). Within the SXhigh tertile the rate of cardiac death was significantly lower in patients treated with the biolimus-eluting stent compared with the sirolimus-eluting stent (4.7% versus 9.6%, HR 0.48; CI 0.23-0.99; p=0.046).. The SXscore when applied to an "all-comers" patient population allows for prospective risk stratification of patients undergoing PCI up to two years follow-up. In addition, the SXscore appears to separate the performance of devices in high risk patient groups.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Heart Diseases; Humans; Male; Middle Aged; Polymers; Proportional Hazards Models; Prospective Studies; Prosthesis Design; Risk Assessment; Risk Factors; Sirolimus; Thrombosis; Time Factors; Tomography, Optical Coherence; Treatment Outcome

Prostaglandin E1 incorporated into lipid microspheres (lipo-PGE1) is effective in the treatment of peripheral vascular disorders and diabetic neuropathy. It is unknown whether it has protective effects in patients with angina pectoris undergoing percutaneous coronary intervention (PCI).. The goal of this pilot study was to investigate whether lipo-PGE1 has protective effects in patients with angina pectoris undergoing PCI.. A single-blinded, randomized controlled trial was conducted in 79 patients with stable or unstable angina pectoris. The control group received standard medical therapy, and the Lipo-PGE1 group (n = 40) received 20 μg/day of lipo-PGE1 intravenously, starting at least 48 h before PCI and continuing for 5 days. Cardiac troponin T (cTnT) and creatine kinase myocardial isoenzyme (CK-MB) were measured before lipo-PGE1 infusion and at 6, 12 and 24 h after PCI.. The cTnT and CK-MB concentrations were lower in the lipo-PGE1 group than in the control group at 6 h (0.15 ± 0.33 vs. 0.43 ± 0.77; 2.87 ± 3.99 vs. 5.64 ± 6.27, respectively; P < 0.05), 12 h (0.20 ± 0.48 vs. 0.54 ± 0.85; 3.58 ± 5.22 vs. 7.45 ± 9.48; P <  0.05) and 24 h (0.18 ± 0.50 vs. 0.50 ± 0.75; 3.15 ± 4.50 vs. 6.16 ± 6.83; P < 0.05). The incidence of postprocedural myocardial injury, defined as an elevation of cTnT more than 0.1 ng/ml or CK-MB more than 5.0 ng/ml, was less in the PGE1 group than in the control group (30 vs. 54%; 13 vs. 31%, respectively; P < 0.05). Lipo-PGE1 was well tolerated and there were no serious adverse events or side-effects.. Lipo-PGE1 treatment appears to reduce myocardial injury following elective PCI in angina patients.

Topics: Aged; Alprostadil; Analysis of Variance; Angina Pectoris; Angina, Unstable; Angioplasty, Balloon, Coronary; Biomarkers; Cardiovascular Agents; Chi-Square Distribution; China; Coronary Angiography; Creatine Kinase, MB Form; Drug Administration Schedule; Female; Heart Diseases; Humans; Infusions, Intravenous; Liposomes; Male; Microspheres; Middle Aged; Pilot Projects; Single-Blind Method; Time Factors; Treatment Outcome; Troponin T

We report 2-year outcomes in a large unselected drug-eluting stent population (N=7,492) in the TAXUS Express2 ARRIVE post-market surveillance programme (101 U.S. sites).. No specific inclusion/exclusion criteria were mandated; patients enrolled at procedure initiation. Two-year follow-up was 94%, with independent adjudication of major cardiac events, monitoring of patients with cardiac events and an additional 10-20% sample by site. Most ARRIVE cases (64%, n=4,794) typified expanded use based on patient/lesion characteristics outside the simple use (single vessel/stent) pivotal trial populations. These expanded use patients had higher 2-year rates than simple use patients for mortality (7.8% vs. 4.2%, P<0.001), myocardial infarction (MI, 3.9% vs. 2.2%, P<0.001), target lesion revascularisation (TLR, 9.2% vs. 5.4%, P<0.001), and stent thrombosis (3.3% vs. 1.4%, P<0.001). Among subgroups with renal disease, chronic total occlusion (CTO), lesion >28 mm, reference vessel diameter (RVD) <2.5 mm, multivessel stenting, acute MI, bifurcation, vein graft, or in-stent restenosis, TLR ranged from 3.8% to 8.9% in year one, and from 1.3% to 6.0% during year two.. Mortality and stent-related events were higher in expanded use than simple use patients in the pivotal trials. ARRIVE provides a detailed estimate of procedural and 2-year outcomes in such real-world patients.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Coronary Restenosis; Coronary Thrombosis; Drug-Eluting Stents; Female; Heart Diseases; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Product Surveillance, Postmarketing; Proportional Hazards Models; Prosthesis Design; Registries; Risk Assessment; Time Factors; Treatment Outcome; United States

To improve medication adherence in cardiac patients, in partnership with a safety-net provider, this research team developed and evaluated a low-literacy medication education tool.. Using principles of community-based participatory research, the team developed a prototype of a low-literacy hospital discharge medication education tool, customizable for each patient, featuring instruction-specific icons and pictures of pills. In 2007, a randomized controlled clinical trial was performed, testing the tool's effect on posthospitalization self-reported medication adherence and knowledge, 2 weeks postdischarge in English- and Spanish-speaking safety-net inpatients. To validate the self-report measure, 4 weeks postdischarge, investigators collected self-reports of the number of pills remaining for each medication in a subsample of participants. Nurses rated tool acceptability.. Among the 166/210 eligible participants (79%) completing the Week-2 interview, self-reported medication adherence was 70% (95% CI=62%, 79%) in intervention participants and 78% (95% CI=72%, 84%) in controls (p=0.13). Among the 85 participants (31%) completing the Week-4 interview, self-reported pill counts indicated high adherence (greater than 90%) and did not differ between study arms. Self-reported adherence was correlated with self-reported pill count in intervention participants (R=0.5, p=0.004) but not in controls (R=0.07, p=0.65). There were no differences by study arm in medication knowledge. The nurses rated the tool as highly acceptable.. Although the evaluation did not demonstrate the tool to have any effect on self-reported medication adherence, patients who received the schedule self-reported their medication adherence more accurately, perhaps indicating improved understanding of their medication regimen and awareness of non-adherence.

Topics: Adult; Aged; Attitude of Health Personnel; Cardiovascular Agents; Comprehension; Female; Health Literacy; Heart Diseases; Hospitals, Urban; Humans; Male; Medication Adherence; Middle Aged; Nurses; Patient Discharge; Patient Education as Topic

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

Perioperative myocardial ischemia occurs in 35% of unselected elderly patients undergoing hip fracture surgery. Perioperative epidural analgesia may reduce the incidence of adverse cardiac events.. The effect of early administration of epidural analgesia during the stressful period, on cardiac events was evaluated in a prospective randomized study in 68 patients with hip fractures who either had known coronary artery disease or were at high risk for coronary artery disease. On admission to the emergency room, patients were assigned to receive a usual care analgesic regimen (intramuscular meperidine, control group, n = 34) or continuous epidural infusion of local anesthetic and opioid (epidural group, n = 34). Monitoring in the preoperative period included a preoperative history and physical examination, daily assessment of cardiac adverse events, serial electrocardiograms, cardiac enzymes, and pain scores.. Preoperative adverse cardiac events were significantly more prevalent in the control group compared with the epidural group (7 of 34 0 of 34; = 0.01). Adverse cardiac events included fatal myocardial infarction in three, fatal congestive heart failure in one, nonfatal congestive heart failure in one, and new onset atrial fibrillation in two. The incidence of intraoperative and postoperative adverse cardiac events was similar for the two groups. The significant difference between groups in the incidence of preoperative cardiac events prompted interruption of the study after the planned interim analysis.. The authors' data indicate that compared with conventional analgesia, early administration of continuous epidural analgesia is associated with a lower incidence of preoperative adverse cardiac events in elderly patients with hip fracture who have or are at risk for coronary artery disease. Preoperative epidural analgesia may be advantageous for this surgical population.

Topics: Aged; Aged, 80 and over; Analgesia, Epidural; Analgesics, Opioid; Anesthesia; Anesthetics, Local; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Disease; Female; Heart Diseases; Heart Failure; Hip Fractures; Humans; Injections, Intramuscular; Male; Orthopedic Procedures; Pain Measurement; Postoperative Period; Preoperative Care; Risk Factors; Treatment Outcome

Dexrazoxane (DEX) selectively blocks the development of irreversible diffuse myocardial toxicity induced by anthracyclines and related antitumor agents, such as mitoxantrone (MTX). Therefore, daunorubicin (DNR) should not be administered to patients with cumulative DNR doses higher than 550 to 700 mg/m2, which we used for remission induction and consolidation therapy in patients with acute myeloid leukemia (AML). To administer further doses of anthracyclines without risks in seven relapsed AML patients and in one patient with impaired heart functions receiving consolidation therapy, we used DEX as a cardioprotective agent. Patients received DEX 30 minutes before DNR 45 mg/m2 or MTX 10 mg/m2 in doses eight to 13 times higher (DNR) or 30 to 60 times higher (MTX) in the treatment cycle with 10 high doses (2,000 mg/m2/12 hr) of cytosine arabinoside plus two doses of DNR or MTX on the fourth and fifth day. When this cycle was used as reinduction therapy, complete remission was achieved in all five cases. A cycle of MTX and etoposide was given three times with DEX as consolidation. Myelotoxicity of the treatment cycles with DEX was similar to the cycles without it. Two patients received cumulative anthracyclines doses corresponding to more than 1,300 and 1,000 mg/m2 of DNR, respectively; the remaining five relapsed patients received 550 to 850 mg/m2 of DNR, all without signs of cardiac toxicity. Delayed administration of DEX after cumulative doses of DNR 500 mg/m2 in AML patients at relapse provides cardioprotection against DNR or MTX in combination with high doses of cytosine arabinoside. This type of chemotherapy seems to be effective for remission induction in relapsed, heavily pretreated AML patients or in patients with impaired heart functions.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cardiovascular Agents; Daunorubicin; Female; Heart Diseases; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mitoxantrone; Razoxane

Although originally developed as an antitumor agent in the 1970s, dexrazoxane (DEX) is currently used as a cardioprotective agent in combination with doxorubicin (DOX). Due to concerns about anthracycline-induced cardiotoxicity at higher cumulative doses, many investigators have chosen to administer DOX by prolonged infusion. Therefore, with the ultimate goal of combining infusional DEX and DOX, we performed a phase I study of intravenous DEX alone as a 96-hour infusion. Surprisingly, the maximum tolerated dose of DEX identified in this study was 10- to 15-fold lower than previously determined using different schedules of administration. Results of pharmacokinetic studies in support of the trial have found that steady-state DEX plasma concentrations in the range of 4 to 5 micromol/L can be achieved safely. Because previous experiments have explored the ability of DEX to inhibit the catalytic activity topoisomerase II at low micromolar concentrations and due to a lack of in vitro cytotoxicity data for long-term exposures, we performed further laboratory studies to provide a context for our pharmacokinetic findings. As a result of these correlative studies, we have found that prolonged exposures to DEX are cytotoxic to human leukemic cells at concentrations that are clinically achievable.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cardiovascular Agents; Doxorubicin; Heart Diseases; Humans; Razoxane; Topoisomerase II Inhibitors

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

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

Dexrazoxane was found effective in reducing doxorubicin cardiotoxicity when given at a dose ratio (dexrazoxane: doxorubicin) of 20:1. Preclinical studies indicated that dexrazoxane at a dose ratio of 10 to 15:1 also protected against epirubicin-induced cardiotoxicity. The main objective of this study was to investigate the efficacy of dexrazoxane, given at a dose ratio of 10:1 against epirubicin cardiotoxicity.. One hundred sixty-two advanced breast cancer patients were randomized to receive epirubicin-based chemotherapy with or without dexrazoxane. Patients who had previously received adjuvant chemotherapy that contained anthracyclines were treated with cyclophosphamide 600 mg/m2 intravenously (IV), epirubicin 60 mg/m2 IV, and fluorouracil 600 mg/m2 IV, on day 1 every 3 weeks. The other patients were treated with epirubicin 120 mg/m2 IV on day 1 every 3 weeks. Cardiac toxicity was defined as clinical signs of congestive heart failure, a decrease in resting left ventricular ejection fraction (LVEF) to < or = 45%, or a decrease from baseline resting LVEF of > or = 20 EF units.. One hundred sixty patients were evaluated. Cardiotoxicity was recorded in 18 of 78 patients (23.1%) in the control arm and in six of 82 (7.3%) in the dexrazoxone arm. The cumulative probability of developing cardiotoxicity was significantly lower in dexrazoxane-treated patients than in control patients (P = .006; odds ratio, 0.29; 95% confidence limit [CL], 0.09 to 0.78). Noncardiac toxicity, objective response, progression-free survival, and overall survival were similar in both arms.. Dexrazoxane given at a dexrazoxane:epirubicin dose ratio of 10:1 protects against epirubicin-induced cardiotoxicity and does not affect the clinical activity and the noncardiac toxicity of epirubicin. The clinical use of dexrazoxane should be recommended in patients whose risk of developing cardiotoxicity could hamper the eventual use and possible benefit of epirubicin.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiovascular Agents; Epirubicin; Female; Heart Diseases; Humans; Middle Aged; Razoxane

Anthracyclines are among the most effective and commonly-prescribed antitumor agents but have dose-limiting cumulative cardiotoxicity. We performed a pharmacoeconomic evaluation of the ability of dexrazoxane to prevent cardiac-related adverse events in patients with Stage IIIB or IV metastatic breast cancer who were treated with a median of 10 cycles of intravenous FAC (5-fluorouracil, doxorubicin and cyclophosphamide) at doses of 500/50/500 mg/m2 respectively. Dexrazoxane was given at 500 mg/m2 commencing at the seventh cycle of treatment. We determined the cost of each cardiac event prevented and the cost of each additional life-year saved by dexrazoxane use. The cost per cardiac event prevented was CDN $5745 and the cost per additional life-year saved was CDN $2856. With the increasing use of anthracyclines in Stages I and II breast cancer, these favorable clinical and economic results may broaden the range of therapeutic possibilities for anthracyclines in adjuvant and metastatic therapy of breast cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiovascular Agents; Cost-Benefit Analysis; Cyclophosphamide; Decision Support Techniques; Doxorubicin; Economics, Pharmaceutical; Female; Fluorouracil; Health Care Costs; Heart; Heart Diseases; Humans; Markov Chains; Middle Aged; Models, Economic; Neoplasm Staging; Razoxane; Sensitivity and Specificity

1. Cardiologists and pharmacists at the University Hospital of Wales collaborated to write 20 individual leaflets incorporating guidelines for a range of drugs used in the treatment of cardiology patients. The Plain English Campaign advised on the intelligibility and presentation of the information. 2. One hundred and twenty-five patients from the Regional Cardiology Unit, University Hospital of Wales were randomly allocated to receive usual verbal counselling about their drug treatment with or without an individualised drug information wallet. Two weeks after discharge from hospital patients completed a postal questionnaire to determine their satisfaction with the information about their drug treatment and their understanding of it. Forty-nine questionnaires were returned from the leaflet group and 52 from the control group. 3. The provision of written guidelines resulted in significant improvements in patients' satisfaction with their drug treatment (chi 2 = 33.3, P less than 0.001) and their understanding of it (P less than 0.001, Mann-Whitney test). Overall, patients who received leaflets were more likely to be aware of the potential side effects of their drugs but less likely to be apprehensive about them. Succinct guidelines concerning drug therapy can be assimilated by cardiology patients and provide them with a permanent record for future reference.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Agents; Communication; Consumer Behavior; Female; Heart Diseases; Humans; Male; Middle Aged; Patient Education as Topic

The energy used by the heart is generated mainly by the metabolism of fatty acids and glucose. Trimetazidine (TMZ) inhibits fatty acid metabolism and is used for the treatment of heart diseases such as heart failure. 3-Bromopyruvate (3-BrPA) can suppress glucose metabolism, and it is considered a promising candidate agent for tumor therapy. Because TMZ and 3-BrPA can separately inhibit the 2 main cardiac energy sources, it is necessary to investigate the effects of 3-BrPA combined with TMZ on the heart. Forty male Wistar rats were randomly divided into 4 groups: a control group, a TMZ group, a 3-BrPA group, and a 3-BrPA + TMZ group. Weight was recorded every day, and echocardiography was performed 14 days later. Heart function, the levels of adenosine triphosphate, oxidative stress-related factors (ROS, glutathione, oxidized glutathione, malondialdehyde, superoxide dismutase and total antioxidant capacity), and apoptosis in heart tissues were assessed to evaluate the effects of 3-BrPA and TMZ on the heart. In our study, no obvious changes occurred in the 3-BrPA group or the TMZ group compared with the control group. The combination of 3-BrPA and TMZ worsened heart function, decreased adenosine triphosphate levels, and increased oxidative stress and myocardial apoptosis. In conclusion, 3-BrPA and TMZ are not recommended for concurrent use.

Topics: Adenosine Triphosphate; Animals; Apoptosis; Cardiotoxicity; Cardiovascular Agents; Energy Metabolism; Enzyme Inhibitors; Heart Diseases; Male; Myocytes, Cardiac; Oxidative Stress; Pyruvates; Rats, Wistar; Signal Transduction; Trimetazidine; Ventricular Function, Left

Diabetes is a serious global health concern which severely affected public health as well as socio-economic growth worldwide. Scutellarin (SCU), a bioactive flavonoid, is known for its efficacious action against a range of ailments including cardiovascular problems. The present study was conducted to find out possible protective effect and its associated mechanisms of SCU on experimental type 2 diabetes-induced cardiac injury.. Type 2 diabetes was induced by treating animals with high fat diet for 4 weeks and a single intraperitoneal dose (35 mg/kg body weight) of streptozotocin and diabetic animals received SCU (10 or 20 mg/kg/day) for 6 weeks.. Scutellarin attenuated type 2 diabetes-induced hyperglycemia, bodyweight loss, hyperlipidaemia, cardiac functional damage with histopathological alterations and fibrosis. Scutellarin treatment to type 2 diabetic mice ameliorated oxidative stress, inflammatory status and apoptosis in heart. Furthermore, the underlying mechanisms for such mitigation of oxidative stress, inflammation and apoptosis in heart involved modulation of Nrf2/Keap1 pathway, TLR4/MyD88/NF-κB mediated inflammatory pathway and intrinsic (mitochondrial) apoptosis pathway, respectively.. The current findings suggest that SCU is effective in protecting type 2 diabetes-induced cardiac injury by attenuating oxidative stress and inflammatory responses and apoptosis, and it is also worth considering the efficacious potential of SCU to treat diabetic cardiomyopathy patients.

Topics: Animals; Apigenin; Apoptosis; Biomarkers; Blood Glucose; Body Weight; Cardiovascular Agents; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Dose-Response Relationship, Drug; Gene Expression Regulation; Glucuronates; Heart Diseases; Inflammation; Lipids; Male; Mice; Oxidative Stress; RNA, Messenger

Background There is no clinical guidance on treatment in patients with non-ischemic myocardial injury and type 2 myocardial infarction (T2MI). Methods and Results In a cohort of 22 589 patients in the emergency department at Karolinska University Hospital in Sweden during 2011 to 2014 we identified 3853 patients who were categorized into either type 1 myocardial infarction, T2MI, non-ischemic acute and chronic myocardial injury. Data from all dispensed prescriptions within 180 days of the visit to the emergency department were obtained concerning β-blockers, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, statins, and platelet inhibitors. We estimated adjusted hazard ratios (HR) with 95% CI for all-cause mortality in relationship to the number of medications (categorized into 0-1 [referent], 2-3 and 4 medications) in the groups of myocardial injury. In patients with T2MI, treatment with 2 to 3 and 4 medications was associated with a 50% and 56% lower mortality, respectively (adjusted HR [95% CI], 0.50 [0.25-1.01], and 0.43 [0.19-0.96]), while corresponding associations in patients with acute myocardial injury were 24% and 29%, respectively (adjusted HR [95% CI], 0.76 [0.59-0.99] and 0.71 [0.5-1.02]), and in patients with chronic myocardial injury 27% and 37%, respectively (adjusted HR [95% CI], 0.73 [0.58-0.92] and 0.63 [0.46-0.87]). Conclusions Patients with T2MI and non-ischemic acute or chronic myocardial injury are infrequently prescribed common cardiovascular medications compared with patients with type 1 myocardial infarction. However, treatment with guideline recommended drugs in patients with T2MI and acute or chronic myocardial injury is associated with a lower risk of death after adjustment for confounders.

Topics: Aged; Cardiovascular Agents; Cohort Studies; Emergency Service, Hospital; Female; Guideline Adherence; Heart Diseases; Humans; Male; Mortality; Myocardial Infarction; Outcome Assessment, Health Care; Practice Guidelines as Topic; Practice Patterns, Physicians'; Sweden

Topics: Animal Testing Alternatives; Biomedical Research; Cardiovascular Agents; Cells, Cultured; Heart Diseases; Humans; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Pharmacology

Cardiovascular risk factors and usage of cardiovascular medication are prevalent among coronavirus disease 2019 (COVID-19) patients. Little is known about the cardiovascular implications of COVID-19. The goal herein, was to evaluate the prognostic impact of having heart disease (HD) and taking cardiovascular medications in a population diagnosed of COVID-19 who required hospitalization. Also, we studied the development of cardiovascular events during hospitalization.. Consecutive patients with definitive diagnosis of COVID-19 made by a positive real time- -polymerase chain reaction of nasopharyngeal swabs who were admitted to the hospital from March 15 to April 14 were included in a retrospective registry. The association of HD with mortality and with mortality or respiratory failure were the primary and secondary objectives, respectively.. A total of 859 patients were included in the present analysis. Cardiovascular risk factors were related to death, particularly diabetes mellitus (hazard ratio in the multivariate analysis: 1.810 [1.159- -2.827], p = 0.009). A total of 113 (13.1%) patients had HD. The presence of HD identified a group of patients with higher mortality (35.4% vs. 18.2%, p < 0.001) but HD was not independently related to prognosis; renin-angiotensin-aldosterone system inhibitors, calcium channel blockers, diuretics and beta-blockers did not worsen prognosis. Statins were independently associated with decreased mortality (0.551 [0.329-0.921], p = 0.023). Cardiovascular events during hospitalization identified a group of patients with poor outcome (mortality 31.8% vs. 19.3% without cardiovascular events, p = 0.007).. The presence of HD is related to higher mortality. Cardiovascular medications taken before admission are not harmful, statins being protective. The development of cardiovascular events during the course of the disease is related to poor outcome.

Topics: Aged; Cardiovascular Agents; Comorbidity; COVID-19; Female; Heart Diseases; Humans; Male; Pandemics; Prognosis; Retrospective Studies; SARS-CoV-2

Topics: Animals; Cardiovascular Agents; Cyclic GMP; Cyclic GMP-Dependent Protein Kinase Type I; Heart Diseases; Humans; Myocardium; Second Messenger Systems

Topics: Algorithms; Antiviral Agents; Arrhythmias, Cardiac; Betacoronavirus; Cardiovascular Agents; Coronavirus Infections; COVID-19; Electrocardiography; Heart Diseases; Humans; Pandemics; Pneumonia, Viral; Risk Factors; SARS-CoV-2

The human heart requires a complex ensemble of specialized cell types to perform its essential function. A greater knowledge of the intricate cellular milieu of the heart is critical to increase our understanding of cardiac homeostasis and pathology. As recent advances in low-input RNA sequencing have allowed definitions of cellular transcriptomes at single-cell resolution at scale, we have applied these approaches to assess the cellular and transcriptional diversity of the nonfailing human heart.. Microfluidic encapsulation and barcoding was used to perform single nuclear RNA sequencing with samples from 7 human donors, selected for their absence of overt cardiac disease. Individual nuclear transcriptomes were then clustered based on transcriptional profiles of highly variable genes. These clusters were used as the basis for between-chamber and between-sex differential gene expression analyses and intersection with genetic and pharmacologic data.. We sequenced the transcriptomes of 287 269 single cardiac nuclei, revealing 9 major cell types and 20 subclusters of cell types within the human heart. Cellular subclasses include 2 distinct groups of resident macrophages, 4 endothelial subtypes, and 2 fibroblast subsets. Comparisons of cellular transcriptomes by cardiac chamber or sex reveal diversity not only in cardiomyocyte transcriptional programs but also in subtypes involved in extracellular matrix remodeling and vascularization. Using genetic association data, we identified strong enrichment for the role of cell subtypes in cardiac traits and diseases. Intersection of our data set with genes on cardiac clinical testing panels and the druggable genome reveals striking patterns of cellular specificity.. Using large-scale single nuclei RNA sequencing, we defined the transcriptional and cellular diversity in the normal human heart. Our identification of discrete cell subtypes and differentially expressed genes within the heart will ultimately facilitate the development of new therapeutics for cardiovascular diseases.

Topics: Adipocytes; Adult; Aged; Cardiovascular Agents; Endothelial Cells; Fibroblasts; Gene Ontology; Heart; Heart Atria; Heart Diseases; Heart Ventricles; Homeostasis; Humans; Lymphocyte Subsets; Macrophages; Microfluidic Analytical Techniques; Middle Aged; Myocardium; Myocytes, Cardiac; Myocytes, Smooth Muscle; Pericytes; RNA-Seq; Sex Characteristics; Single-Cell Analysis; Transcription, Genetic; Transcriptome

Topics: Aged, 80 and over; Antineoplastic Agents; Benzamides; Cardiovascular Agents; Digoxin; Drug Monitoring; Heart Diseases; Humans; Immunoassay; Luminescent Measurements; Male; Middle Aged; Nitriles; Phenylthiohydantoin; Prostatic Neoplasms

Topics: Age Factors; Aging; Animals; Biomedical Research; Cardiology; Cardiovascular Agents; Genetic Therapy; Heart Diseases; Humans; Myocardium; RNA, Untranslated

Levosimendan (LEVO) a clinically-used inodilator, exerts multifaceted cardioprotective effects. Case-studies indicate protection against doxorubicin (DXR)-induced cardiotoxicity, but this effect remains obscure. We investigated the effect and mechanism of different regimens of levosimendan on sub-chronic and chronic doxorubicin cardiotoxicity.. Based on preliminary in vivo experiments, rats serving as a sub-chronic model of doxorubicin-cardiotoxicity and were divided into: Control (N/S-0.9%), DXR (18 mg/kg-cumulative), DXR+LEVO (LEVO, 24 μg/kg-cumulative), and DXR+LEVO (acute) (LEVO, 24 μg/kg-bolus) for 14 days. Protein kinase-B (Akt), endothelial nitric oxide synthase (eNOS), and protein kinase-A and G (PKA/PKG) pathways emerged as contributors to the cardioprotection, converging onto phospholamban (PLN). To verify the contribution of PLN, phospholamban knockout (PLN-/-) mice were assigned to PLN-/-/Control (N/S-0.9%), PLN-/-/DXR (18 mg/kg), and PLN-/-/DXR+LEVO (ac) for 14 days. Furthermore, female breast cancer-bearing (BC) mice were divided into: Control (normal saline 0.9%, N/S 0.9%), DXR (18 mg/kg), LEVO, and DXR+LEVO (LEVO, 24 μg/kg-bolus) for 28 days. Echocardiography was performed in all protocols. To elucidate levosimendan's cardioprotective mechanism, primary cardiomyocytes were treated with doxorubicin or/and levosimendan and with N omega-nitro-L-arginine methyl ester (L-NAME), DT-2, and H-89 (eNOS, PKG, and PKA inhibitors, respectively); cardiomyocyte-toxicity was assessed. Single bolus administration of levosimendan abrogated DXR-induced cardiotoxicity and activated Akt/eNOS and cAMP-PKA/cGMP-PKG/PLN pathways but failed to exert cardioprotection in PLN-/- mice. Levosimendan's cardioprotection was also evident in the BC model. Finally, in vitro PKA inhibition abrogated levosimendan-mediated cardioprotection, indicating that its cardioprotection is cAMP-PKA dependent, while levosimendan preponderated over milrinone and dobutamine, by ameliorating calcium overload.. Single dose levosimendan prevented doxorubicin cardiotoxicity through a cAMP-PKA-PLN pathway, highlighting the role of inotropy in doxorubicin cardiotoxicity.

Topics: Animals; Antibiotics, Antineoplastic; Calcium Signaling; Calcium-Binding Proteins; Cardiotoxicity; Cardiovascular Agents; Cells, Cultured; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Dose-Response Relationship, Drug; Doxorubicin; Female; Heart Diseases; Male; Mammary Neoplasms, Experimental; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Myocardial Contraction; Myocytes, Cardiac; Nitric Oxide Synthase Type III; Proto-Oncogene Proteins c-akt; Rats, Wistar; Simendan; Time Factors

Topics: Acute Coronary Syndrome; Adult; Biopsy; Cardiovascular Agents; Diagnostic Errors; Echocardiography, Doppler, Color; Female; Heart Diseases; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Multimodal Imaging; Myositis; Predictive Value of Tests; Tomography, Optical Coherence

Topics: Acetic Acid; Antineoplastic Agents; Cardiovascular Agents; Heart Diseases; Humans; Neoplasms; Oxalates

The aim of this study is to assess the prevalence of polypharmacy, inappropriate drug use, and drug-drug interactions (DDIs) in elderly patients presenting at outpatient cardiology clinics in Turkey.. The EPIC (Epidemiology of Polypharmacy and Potential Drug-Drug Interactions in Elderly Cardiac Outpatients) study will be an observational, real-world, multicenter study conducted to evaluate DDIs and polypharmacy in elderly cardiac outpatients. All consecutive patients (aged ≥65 years) admitted to outpatient cardiology clinics between July 30, 2018 and July 30, 2019 who provide written, informed consent will be enrolled. A total of approximately 5000 patients are to be enrolled in this non-interventional study. All of the data will be collected at one point in time and current clinical practice will be evaluated (ClinicalTrials.gov NCT03370523).. Patient demographics, comorbid disease characteristics, laboratory test results, and details of medication use will be collected using self-reports and medical records. The severity of comorbid disease will be recorded and scored according to Charlson Comorbidity Index (CCI) and patients will be divided into 3 groups: mild, those with a CCI score of 1-2; moderate, those with a CCI score of 3-4; and severe, those with a CCI score of ≥5. Polypharmacy will be defined as the use of 5 or more medications at one time. DDIs will be determined using the Lexicomp Online drug interaction screening tool and potentially inappropriate medications will be defined based on the 2015 update of the Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. Severe drug interactions will be defined as those in category D or X.. EPIC will be the first large-scale study in Turkey to evaluate polypharmacy, potentially inappropriate medications, and DDIs in elderly cardiac outpatients in a real-world clinical setting.

Topics: Aged; Aged, 80 and over; Ambulatory Care; Cardiovascular Agents; Clinical Trials as Topic; Drug Interactions; Heart Diseases; Humans; Polypharmacy; Potentially Inappropriate Medication List; Research Design

Levosimendan is a calcium sensitizer and adenosine triphosphate-dependent potassium channel opener, which exerts sustained hemodynamic, symptomatic, and organ-protective effects. It is registered for the treatment of acute heart failure, and when inotropic support is considered appropriate. In the past 15 years, levosimendan has been widely used in clinical practice and has also been tested in clinical trials to stabilize at-risk patients undergoing cardiac surgery. Recently, 3 randomized, placebo-controlled, multicenter studies (LICORN, CHEETAH, and LEVO-CTS) have been published reporting on the perioperative use of levosimendan in patients with compromised cardiac ventricular function. Taken together, many smaller trials conducted in the past suggested beneficial outcomes with levosimendan in perioperative settings. By contrast, the latest 3 studies were neutral or inconclusive. To understand the reasons for such dissimilarity, a group of experts from Austria, Belgium, Finland, France, Germany, Italy, Switzerland, and Russia, including investigators from the 3 most recent studies, met to discuss the study results in the light of both the previous literature and current clinical practice. Despite the fact that the null hypothesis could not be ruled out in the recent multicenter trials, we conclude that levosimendan can still be viewed as a safe and effective inodilator in cardiac surgery.

Topics: Cardiac Surgical Procedures; Cardiovascular Agents; Clinical Decision-Making; Congresses as Topic; Consensus; Evidence-Based Medicine; Heart Diseases; Humans; Patient Selection; Perioperative Care; Randomized Controlled Trials as Topic; Risk Factors; Simendan; Treatment Outcome

Topics: Bed Rest; Cardiology; Cardiovascular Agents; Heart Diseases; History, 20th Century; History, 21st Century; Humans; Length of Stay; Myocardial Infarction

We aimed to determine the effect of aquatic cycling and different levels of immersion on respiratory responses in healthy and heart disease (HD) volunteers. Thirty-four age matched volunteers, 21 HD and 13 healthy controls (HC) took part in this study. The ventilatory pattern, phase 1V

Topics: Aged; Bicycling; Carbon Dioxide; Cardiovascular Agents; Exercise Therapy; Female; Heart Diseases; Humans; Immersion; Male; Middle Aged; Respiration; Tidal Volume; Water

Cardiomyocytes from human pluripotent stem cells (hPSCs-CMs) could revolutionise biomedicine. Global burden of heart failure will soon reach USD $90bn, while unexpected cardiotoxicity underlies 28% of drug withdrawals. Advances in hPSC isolation, Cas9/CRISPR genome engineering and hPSC-CM differentiation have improved patient care, progressed drugs to clinic and opened a new era in safety pharmacology. Nevertheless, predictive cardiotoxicity using hPSC-CMs contrasts from failure to almost total success. Since this likely relates to cell immaturity, efforts are underway to use biochemical and biophysical cues to improve many of the ~30 structural and functional properties of hPSC-CMs towards those seen in adult CMs. Other developments needed for widespread hPSC-CM utility include subtype specification, cost reduction of large scale differentiation and elimination of the phenotyping bottleneck. This review will consider these factors in the evolution of hPSC-CM technologies, as well as their integration into high content industrial platforms that assess structure, mitochondrial function, electrophysiology, calcium transients and contractility. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

Topics: Biomedical Research; Cardiovascular Agents; Cell Differentiation; Cell Lineage; Cell Proliferation; Cells, Cultured; Drug Discovery; Genotype; Heart Diseases; High-Throughput Screening Assays; Humans; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Phenotype; Risk Assessment; Toxicity Tests

Both biomedical research and clinical practice rely on complex datasets for the physiological and genetic characterization of human hearts in health and disease. Given the complexity and variety of approaches and recordings, there is now growing recognition of the need to embed computational methods in cardiovascular medicine and science for analysis, integration and prediction. This paper describes a Workshop on Computational Cardiovascular Science that created an international, interdisciplinary and inter-sectorial forum to define the next steps for a human-based approach to disease supported by computational methodologies. The main ideas highlighted were (i) a shift towards human-based methodologies, spurred by advances in new in silico, in vivo, in vitro, and ex vivo techniques and the increasing acknowledgement of the limitations of animal models. (ii) Computational approaches complement, expand, bridge, and integrate in vitro, in vivo, and ex vivo experimental and clinical data and methods, and as such they are an integral part of human-based methodologies in pharmacology and medicine. (iii) The effective implementation of multi- and interdisciplinary approaches, teams, and training combining and integrating computational methods with experimental and clinical approaches across academia, industry, and healthcare settings is a priority. (iv) The human-based cross-disciplinary approach requires experts in specific methodologies and domains, who also have the capacity to communicate and collaborate across disciplines and cross-sector environments. (v) This new translational domain for human-based cardiology and pharmacology requires new partnerships supported financially and institutionally across sectors. Institutional, organizational, and social barriers must be identified, understood and overcome in each specific setting.

Topics: Animals; Biomarkers; Cardiac Imaging Techniques; Cardiology; Cardiotoxicity; Cardiovascular Agents; Cooperative Behavior; Diffusion of Innovation; Electrophysiologic Techniques, Cardiac; Heart Diseases; Humans; Interdisciplinary Communication; Models, Cardiovascular; Patient-Specific Modeling; Pharmacology; Predictive Value of Tests; Prognosis; Public-Private Sector Partnerships; Translational Research, Biomedical

There is accumulating evidence that the cardioprotective effects of stem cells are predominantly mediated by the release of a blend of factors, possibly clustered into extracellular vesicles, which harness endogenous repair pathways. The clinical translation of this concept requires the identification of the cell-secreted signaling biomolecules and an appropriate transfer method. The study by Wei and colleagues has addressed these 2 requirements by showing that the epicardial delivery of a collagen patch loaded with the cardiokine follistatin-like 1 improved left ventricular function in animal models of myocardial infarction. Beyond the choice of the factor and its vehicle, these data may open a new therapeutic path whereby the functionalization of biomaterials by bioactive compounds could successfully substitute for the current cell transplantation-based strategy.

Topics: Animals; Cardiovascular Agents; Diffusion of Innovation; Drug Carriers; Follistatin-Related Proteins; Heart Diseases; Humans; Myocardium; Phenotype; Recovery of Function; Regeneration; Regenerative Medicine; Signal Transduction; Stem Cell Transplantation; Stem Cells; Treatment Outcome

To evaluate the role of routine troponin surveillance in patients undergoing major noncardiac surgery, unblinded screening with cardiac consultation per protocol was implemented at a tertiary care center. In this study, we evaluated 1-year mortality, causes of death, and consequences of cardiac consultation of this protocol.. This observational cohort included 3224 patients ≥60 years old undergoing major noncardiac surgery. Troponin I was measured routinely on the first 3 postoperative days. Myocardial injury was defined as troponin I >0.06 μg/L. Regression analysis was used to determine the association between myocardial injury and 1-year mortality. The causes of death, the diagnoses of the cardiologists, and interventions were determined for different levels of troponin elevation.. Postoperative myocardial injury was detected in 715 patients (22%) and was associated with 1-year all-cause mortality (relative risk [RR] 1.4, P = 0.004; RR 1.6, P < 0.001; and RR 2.2, P < 0.001 for minor, moderate, and major troponin elevation, respectively). Cardiac death within 1 year occurred in 3%, 5%, and 11% of patients, respectively, in comparison with 3% of the patients without myocardial injury (P = 0.059). A cardiac consultation was obtained in 290 of the 715 patients (41%). In 119 (41%) of these patients, the myocardial injury was considered to be attributable to a predisposing cardiac condition, and in 111 patients (38%), an intervention was initiated.. Postoperative myocardial injury was associated with an increased risk of 1-year all-cause but not cardiac mortality. A cardiac consultation with intervention was performed in less than half of these patients. The small number of interventions may be explained by a low suspicion of a cardiac etiology in most patients and lack of consensus for standardized treatment in these patients.

Topics: Aged; Aged, 80 and over; Biomarkers; Blood Transfusion; Cardiovascular Agents; Cause of Death; Chi-Square Distribution; Electrocardiography; Female; Heart Diseases; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardial Revascularization; Odds Ratio; Postoperative Complications; Predictive Value of Tests; Referral and Consultation; Retreatment; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Troponin

Medical management of acute aortic dissections limited to the descending thoracic aorta (AD-desc) is associated with acceptable outcomes. Uncertainty remains about whether acute type B aortic dissections involving the aortic arch (AD-arch) have an increased risk of retrograde extension into the ascending aorta or other dissection-related complications. This study compared outcomes of AD-arch with AD-desc managed medically.. Consecutive patients admitted from 2005 to 2014 with acute aortic dissections not involving the ascending aorta were retrospectively analyzed. Primary end points included dissection-related death and operative intervention.. The study included 99 patients (63% men; mean age, 60 ± 14 years) with acute aortic dissections. Dissections were limited to the aorta distal to the left subclavian artery (AD-desc) in 79 patients (80%), and 20 (20%) had involvement of the left subclavian (n = 16), left common carotid (n = 1), or innominate (n = 3) arteries (AD-arch). Dissections ended proximal to the celiac artery in 30 patients (30%), between the celiac artery and aortic bifurcation in 36 (36%), and distal to the aortic bifurcation in 33 (33%). During medical management, further proximal extension into the arch occurred in two AD-arch patients and one AD-desc patient (P < .05), but proximal dissection into the ascending aorta occurred in only one AD-arch patient with Marfan disease. Compared with patients with AD-desc, those with AD-arch were younger (53 ± 12.5 vs 62 ± 16 years; P < .01) and had more frequent early interventions (40% vs 19%; P = .047), cardiac complications (35% vs 11%; P < .01), and neurologic events (25% vs 6%; P < .01). Seven AD-arch patients (35%) and nine AD-desc patients (11%) died of dissection-related causes (P < .01). Among survivors, late interventions were performed in four of eight AD-arch patients (50%) and in six of 58 AD-desc patients (10%; P = .02). Medical treatment without intervention was successful in four AD-arch patients (20%) and in 52 AD-desc patients (66%; P < .001). Multivariate logistic regression retained arch involvement as the sole predictor of dissection-related death (odds ratio, 4.2; 95% confidence interval, 1.3-13.4) and failure of medical treatment (odds ratio, 7.7; 95% confidence interval, 2.5-29). The distal extent of dissection had no bearing on outcome.. AD-arch dissections are associated with a higher risk of cardiac and neurologic events, need for early intervention, and dissection-related death than AD-desc dissections. Because further proximal dissections into the ascending aorta were rare in this study, medical management appears to be safe as the initial treatment of AD-arch dissections. However, surgeons should be aware of the increased risk of complications and the potential need for urgent interventions in these patients.

Topics: Acute Disease; Adult; Aged; Aorta, Thoracic; Aortic Aneurysm, Thoracic; Aortic Dissection; Aortography; Cardiovascular Agents; Chi-Square Distribution; Disease Progression; Female; Heart Diseases; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Nervous System Diseases; Odds Ratio; Retrospective Studies; Risk Factors; Tennessee; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Vascular Surgical Procedures

Topics: Adult; Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Agents; Female; Heart Diseases; Humans; Male; Middle Aged; Prevalence; Risk Factors; Spain; Young Adult

Defibrillation testing (DT) is considered a standard procedure during implantable cardioverter-defibrillator (ICD) implantation. However, little is known about the factors that are significantly related to patients with high defibrillation threshold (DFT) using the present triad system.. We examined 286 consecutive patients who underwent ICD implantation with a transvenous dual-coil lead and DT from December 2000 to December 2011. We defined patients who required 25 J or more by the implanted device as the high DFT group, and those who required less than 25 J as the normal DFT group. For each patient, assessment parameters included underlying disease, comorbidities, NYHA functional class, drugs, and echocardiographic measures. The high DFT group consisted of 12 patients (4.2%). Multivariate analysis identified 3 independent predictors for high DFT: atrial fibrillation (odds ratio (OR) 4.85, 95% confidence interval (CI) 1.24-22.33, P=0.023), hypertension (OR 4.01, 95% CI 1.08-15.96, P=0.039), thickness of interventricular septum (IVS) >12 mm (OR 4.82, 95% CI 1.17-20.31, P=0.030).. Atrial fibrillation, hypertension and IVS hypertrophy were significantly associated with high DFT. Identification of such patients could help to lower the risk of complications with DT.

Topics: Atrial Fibrillation; Cardiovascular Agents; Combined Modality Therapy; Defibrillators, Implantable; Electrodes; Equipment Design; Female; Heart Diseases; Heart Septum; Humans; Hypertension; Hypertrophy; Male; Middle Aged; Retrospective Studies; Risk Factors; Ventricular Fibrillation

Ambulatory measurement of intrathoracic impedance (ITI) with an implanted device may detect increases in pulmonary fluid retention early, but the clinical utility of this method is not well established. The goal of this study was to test whether conventional ITI-derived parameters can diagnose fluid retention that may cause early stage heart failure (HF).. HF patients implanted with high-energy devices with OptiVol (Medtronic) monitoring were enrolled in this study. Patients were monitored remotely. At both baseline and OptiVol alert, patients were assessed on standard examinations, including analysis of serum brain natriuretic peptide (BNP). From April 2010 to August 2011, 195 patients from 12 institutes were enrolled. There were 154 primary OptiVol alert events. BNP level at the alerts was not significantly different from that at baseline. Given that ITI was inversely correlated with log BNP, we added a criterion specifying that the OptiVol alert is triggered only when ITI decreases by ≥4% from baseline. This change improved the diagnostic potential of increase in BNP at OptiVol alert (sensitivity, 75%; specificity, 88%).. BNP increase could not be identified based on OptiVol alert. Decrease in ITI ≥4% compared with baseline, in addition to the alert, however, may be a useful marker for the likelihood of HF (Clinical trial info: UMIN000003351).

Topics: Acute Disease; Aged; Aged, 80 and over; Algorithms; Biomarkers; Cardiac Resynchronization Therapy; Cardiography, Impedance; Cardiovascular Agents; Clinical Alarms; Combined Modality Therapy; Defibrillators, Implantable; Electric Impedance; Female; Heart Diseases; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Pulmonary Edema; ROC Curve; Telemedicine; Vena Cava, Inferior; Weight Gain

Topics: Autonomic Nervous System; Cardiopulmonary Resuscitation; Cardiovascular Agents; Death, Sudden, Cardiac; Disease Management; Heart; Heart Conduction System; Heart Diseases; Humans; Myocardium

Cardiac cachexia, a loss of lean body mass caused by heart disease, often accompanies congestive heart failure (CHF). Blocking myostatin, which is a protein that inhibits muscle growth, appears to greatly enhance muscle size and strength in rodent models and human clinical trials. The objective of this study was to evaluate a dog-specific myostatin antagonist (CAP-031) in a pilot study to test its safety and efficacy in dogs with CHF and cardiac cachexia.. Dogs with CHF and cardiac cachexia.. Eligible dogs received four weekly subcutaneous injections of CAP-031. Endpoints were body weight, body condition score (BCS, on a 1-9 scale), muscle condition score (MCS, on a five-point scale, where 0 = no muscle loss and 4 = severe muscle loss), appetite, and a quality of life (QOL) score.. Seven dogs with CHF and moderate-to-severe cachexia were enrolled in the study. For the six dogs that completed the study, the median age was 8.8 years (range 6.4-10.6). At baseline, the median body weight was 27.0 kg (range 17.3-62.0), the median BCS was 4 (2-5), and median MCS was 3 (3-4). There were no significant changes in body weight, BCS, appetite, or QOL score. The change in MCS (from a median of 3 at baseline to a median of 2.5 at week 4) was not statistically significant (p = 0.06).. The myostatin antagonist appeared to be well tolerated in most dogs. Earlier identification of cachexia is important, and randomized, controlled trials of myostatin antagonists or other drugs to treat cardiac cachexia are needed.

Topics: Activin Receptors, Type II; Animals; Cachexia; Cardiovascular Agents; Dog Diseases; Dogs; Female; Heart Diseases; Male; Myostatin; Pilot Projects

To describe cardiac involvement in patients with acute thrombotic microangiopathy (TMA).. The case histories of 46 patients with proven TMA, including 17 patients diagnosed with atypical hemolytic uremic syndrome (aHUS) and 29 patients with catastrophic antiphospholipid syndrome (CAPS), were analyzed.. Different documentarily verified signs of cardiac involvement were revealed in 6 (13%) patients (5 and 1 patients diagnosed as having aHUS and CAPS, respectively). Five patients developed myocardial involvement at disease onset in the presence of multiple organ dysfunction.. Cases of cardiac involvement in TMA of various genesis are presented. The exact incidence of myocardial involvement and its prognostic value are unknown so far.. Цель исследования. Описать поражение сердца у больных острой тромботической микроангиопатией (ТМА). Материалы и методы. Проанализировали 46 историй болезни пациентов с доказанной острой ТМА, из которых у 17 диагностирован атипичный гемолитико-уремический синдром (аГУС), у 29 - катастрофический антифосфолипидный синдром (КАФС). Результаты. Различные документально подтвержденные признаки поражения сердца выявлены у 6 (13%) больных (5 - с диагнозом аГУС, 1 - с КАФС). У 5 пациентов вовлечение миокарда развилось в дебюте заболевания в рамках полиорганного поражения. Заключение. Представлены наблюдения поражения сердца при ТМА разного генеза. Точная частота вовлечения миокарда и его прогностическое значение у пациентов с ТМА до настоящего времени неизвестны.

Topics: Acute Disease; Adolescent; Adult; Antiphospholipid Syndrome; Atypical Hemolytic Uremic Syndrome; Cardiovascular Agents; Echocardiography; Electrocardiography; Female; Heart Diseases; Humans; Male; Renal Dialysis; Renal Insufficiency; Thrombotic Microangiopathies; Treatment Outcome

Topics: Anticoagulants; Arrhythmogenic Right Ventricular Dysplasia; Atrial Fibrillation; Benzazepines; Bradycardia; Cardiovascular Agents; Heart Diseases; Hemorrhage; Humans; Ivabradine; Point-of-Care Systems

Cardiac abnormalities attributed to adrenergic surge are common after aneurysmal subarachnoid hemorrhage. Prescribed medications that block adrenergic stimulation may suppress the onset of cardiopulmonary compromise in patients after aneurysmal subarachnoid hemorrhage.. To compare the incidence of early cardiac complications between patients who reported prescribed use of β-blockers and/or angiotensin-converting enzyme inhibitors before aneurysmal subarachnoid hemorrhage and patients who did not.. A retrospective review of 254 adult patients after acute aneurysmal subarachnoid hemorrhage who were enrolled in an existing R01 study. Demographic data and history were obtained from patients'/proxies' reports and charts. Cardiac enzyme levels, 12-lead electrocardiograms, and chest radiographs were obtained on admission. Holter monitoring and echocardiograms were completed as a part of the R01 study.. Patients reporting prescribed use of angiotensin-converting enzyme inhibitors or β-blockers before aneurysmal subarachnoid hemorrhage had more ventricular and supraventricular ectopy on a Holter report than did patients who did not (P < .05). When age, race, sex, and injury (Fisher grade) were controlled for, patients reporting use of β-blockers were 8 times more likely than others to have occasional to frequent ventricular ectopy (P = .02).. No concrete evidence was found that exposure to adrenergic blockade before aneurysmal subarachnoid hemorrhage provides protection from neurocardiac injury.

Topics: Adrenergic beta-Antagonists; Adult; Age Distribution; Aged; Aneurysm, Ruptured; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Female; Heart; Heart Diseases; Humans; Intracranial Aneurysm; Male; Middle Aged; Retrospective Studies; Sex Distribution; Subarachnoid Hemorrhage; Survival Analysis; Young Adult

Many patients suffer from both heart and lung diseases. The choice of medical drugs should not only be driven by the clinical and prognostic effects on the target organ but should also be selected based on the effects on the respective other organ. Beta blockers and statins have both beneficial and harmful effects on the respiratory system. Angiotensin-converting enzyme (ACE) inhibitors and amiodarone can cause severe lung damage. Low-dose thiazides and calcium antagonists are first-line medications in hypertensive asthma patients but beta blockers should be avoided. Theophyline should be used with caution in patients with known cardiac disease. Glucocorticosteroids can cause cardiovascular symptoms while the phosphodiesterase inhibitor roflumilast appears to have no relevant cardiovascular side effects. Anticholinergic drugs have both favorable and unfavorable cardiovascular (side) effects. Short-acting beta-2 sympathomimetic drugs (SABA) and macrolides in particular can trigger arrhythmia and some SABAs are associated with a higher incidence of myocardial infarction. Detailed knowledge of the effects of drugs used for the treatment of lung and heart diseases on the respective other organ and the associated complications and long-term effects are essential in providing optimal medical care to the many patients who present with both respiratory and cardiovascular diseases.

Topics: Cardiovascular Agents; Evidence-Based Medicine; Heart Diseases; Humans; Lung Diseases; Respiratory System Agents; Treatment Outcome

In adult patients, cardiovascular drugs are widely administered in the treatment of numerous diseases. The indications and doses are strictly codified by international Guidelines, which are periodically updated by the American and European Societies of Cardiology. In paediatric patients, however, the situation is substantially different. The lack of large interventional studies on the use of these compounds has led to a greater uncertainty, with a less extensive administration and more limited indications. Furthermore, some important differences in therapeutic approach for the same diseases are present between the U.S. and Europe. The purpose of this Special Issue is to review the pharmacological treatment of certain heart diseases, such as heart failure, and arterial blood pressure, which can result in both adult and pediatric patients [1, 2]. Differences and similarities have been highlighted. Regarding the differences in medical treatment for the same disease in the U.S. and Europe, it has been emphasized that the regulation of drugs is largely determined not only by scientific considerations, but also by other concerns - legal, cultural - which vary in different parts of the world. Such discrepancies are found even in the informational documents provided by pharmaceutical companies (different in USA and Europe for the same drug) and drug agencies (different between FDA and equivalent agencies in Europe). In this issue of Current Medicinal Chemistry, a specific paper is dedicated to the pharmacological treatment of the patency of ductus arteriosus in neonates, which is still a controversial issue. In fact, notwithstanding ibuprofen appears to be lesser dangerous for newborns than indomethacin, with a similar efficacy in closing the ductus; in a number of countries the latter is still administered to all preterm subjects as a prophylactic tool [3]. An unusual case report is the interesting starting point to perform an extensive literature review about the new indications of beta blockers [4]. In this respect, beta blockers, most specifically propranolol, have serendipitously been shown to induce involution of infantile hemangiomas. Mechanisms of action, target doses, formulation, contraindications and cardiovascular monitoring for beta blockers have been analyzed as well. It has recently been demonstrated that preterm birth is negatively associated with an early onset of cardiovascular diseases. Cardiovascular mortality is higher among former preterm ad

Topics: Adult; Cardiovascular Agents; Child; Heart Diseases; Humans; Metabolomics

Pericardial defects are rare in both people and dogs. They may be congenital or acquired in origin, and partial or total in extent. Commonly, pericardial defects are incidental findings at autopsy; however, diagnostic methods such as thoracic radiography and echocardiography can be useful in the ante mortem diagnosis of pericardial defects. This report describes the first case of a dog with syncope, supraventricular tachycardia, and a partial left pericardial defect with herniation of the left auricle for which extensive ante mortem diagnostic information was available. Partial absence of the pericardium should be considered in dogs with disproportionate enlargement of cardiac chambers for which other congenital and acquired heart diseases are ruled out.

Topics: Animals; Cardiovascular Agents; Dog Diseases; Dogs; Electrocardiography; Female; Heart Atria; Heart Diseases; Hernia; Pericardium; Syncope

Topics: Adolescent; Adult; Angiography, Digital Subtraction; Arteriovenous Malformations; Blood Loss, Surgical; Blood Transfusion; Cardiovascular Agents; Female; Heart Diseases; Humans; Lower Extremity; Magnetic Resonance Imaging; Male; Tomography, X-Ray Computed; Treatment Outcome; Vascular Surgical Procedures

Patients' perception of risk and their lifestyle choices are of major importance in the treatment of common chronic diseases. This study reveals determinants for and knowledge about why people accept or reject preventive medical interventions against heart disease.. A representative sample of 40-60-year-old Danish inhabitants was invited to participate in a web-based survey. The respondents were presented with a hypothetical scenario and asked to imagine that they were at an increased risk of heart disease, and subsequently presented with an offer of a preventive medical intervention. The aim was to elicit preference structures when potential patients are presented with different treatment conditions.. About one third of the respondents were willing to accept preventive medical treatment. Respondents with personal experience with heart disease were more likely to accept treatment than respondents with family members with heart disease or no prior experience with heart disease. The willingness to accept treatment was similar for both genders, and when adjusting for experience with heart disease, age was not associated with willingness to accept treatment. Socioeconomic status in terms of lower education was positively associated with acceptance. The price of treatment reduced willingness to accept for the lower income groups, whereas it had no effect in the highest income group. Some 57% of respondents who were willing to accept treatment changed their decision following information on potential side effects.. In accordance with our pre-study hypothesis, individuals with low income were more sensitive to price than individuals with high income. Thus, if the price of preventive medication increases above certain limits, a substantial proportion of the population may refrain from treatment. More than half of the respondents who were initially willing to accept treatment changed their decision when informed about the presence of potential side effects. This is an important observation in relation to risk communication, since most side effects occur very seldom, and a skewed assessment of treatment efficacy compared to risk of side effects may refrain some patients from treatment. Thus, more research is needed to better allow patients to compare treatment efficacy with risk of side effects in quantitative terms.

Topics: Adult; Aged; Cardiovascular Agents; Choice Behavior; Chronic Disease; Commerce; Communication; Data Collection; Denmark; Family; Female; Health Behavior; Heart Diseases; Humans; Internet; Life Style; Male; Middle Aged; Patient Acceptance of Health Care; Risk; Socioeconomic Factors; Treatment Outcome

In order to evaluate the effectiveness mildronate in rehabilitative treatment in connective tissue dysplasia examined 240 patients (24,41 ± 7,62 years, 130 men). All patients were treated with 5 ml of mildronate 10% intravenously for 10 days, then 1 capsule (250 mg), 2 times per day for 4 months. The therapy showed a significant decrease in asthenic complaints, reducing the incidence of violations repolarization I (p<0.05) and II infarction (p<0.05), a significant increase in end-diastolic volume (p<0.05), stroke volume (p<0.05), left ventricular ejection fraction (p<0.05) by echocardiography, increased exercise tolerance with the normalization of reaction to physical stress on a dystonic normotonichesky, improved quality of life. During the treatment was not recorded adverse events in patients receiving the drug. Portability mildronate majority of patients described as good to very good (average 8.67 points).

Topics: Adult; Asthenia; Cardiovascular Agents; Connective Tissue Diseases; Drug Administration Routes; Drug Monitoring; Exercise Tolerance; Female; Heart Diseases; Heart Function Tests; Humans; Male; Methylhydrazines; Myocardial Contraction; Treatment Outcome

Heart disease is the number one killer of women, and studies have shown connections between cardiovascular and oral health. However, interprofessional community-based participatory initiatives promoting women's oral health have received little research attention. This study evaluated the effectiveness of personalized oral health education (POHE) during a free one-day interprofessional women's health promotion event. The objectives were to 1) assess the participants' knowledge about the connection between oral health and heart disease; 2) disseminate information about oral-systemic linkages; 3) encourage comprehensive dental examinations; and 4) evaluate POHE outcomes. West Virginia University School of Dentistry faculty and students delivered POHE to the participants. These POHE instructors were calibrated with a standardized script regarding periodontal disease, health impact of tobacco, xerostomia-inducing medications, and oral hygiene instruction. Immediately prior to and following each POHE session, all the participants (N=165; 100 percent response rate) completed a number-coded questionnaire. The findings showed that the participants' knowledge of oral-systemic health linkages had increased following the POHE. The respondents received oral health kits and were offered discount vouchers toward the cost of a comprehensive oral examination at the dental school. This replicable model may prove useful to other dental schools in promoting women's oral health.

Topics: Aged; Attitude to Health; Bacteremia; Cardiovascular Agents; Dental Care; Female; Health Education, Dental; Health Fairs; Health Promotion; Heart Diseases; Humans; Information Dissemination; Memory Disorders; Middle Aged; Oral Health; Oral Hygiene; Periodontal Diseases; Precision Medicine; Stroke; Tobacco Products; Women's Health; Wound Healing; Xerostomia

Topics: Cardiology; Cardiovascular Agents; Heart Diseases; History, 19th Century; History, 20th Century; Humans; Hypertension

Cardiac fibrosis greatly impairs normal heart function post infarction and there is no effective anti-fibrotic drug developed at present. The current therapies for cardiac infarction mainly take effect by eliminating occlusion in coronary artery by thrombolysis drugs, vascular stent grafting or heart bypass operation, which are capable to provide sufficient blood flow for intact myocardium yet showed subtle efficacy in ameliorating fibrosis condition. The advances of in vitro cell/tissue models open new avenues for drug assessment due to the low cost, good controllability and availability as well as the convenience for operation as compared to the animal models. To our knowledge, no proper biomimetic in vitro cardiac fibrosis model has been reported yet. Here we engineered an in vitro cardiac fibrosis model using heart-derived fibroblasts, and the fibrogenesis was recapitulated by patterning the substrate rigidity which mimicked the mechanical heterogeneity of myocardium post-infarction. Various biomarkers for cardiac fibrosis were assayed to validate the biomimicry of the engineered platform. Subsequent addition of Rho-associated protein kinase (ROCK) pathway inhibitor reduced the ratio of myofibroblasts, indicating the feasibility of applying this platform in screening anti-fibrosis drugs.

Topics: Amides; Animals; Cardiovascular Agents; Cell Proliferation; Cells, Cultured; Drug Discovery; Fibrosis; Heart Diseases; Male; Mechanotransduction, Cellular; Mice; Models, Cardiovascular; Myofibroblasts; NIH 3T3 Cells; Pyridines; Rats, Sprague-Dawley

Peripartum cardiomyopathy (PPCM) is a rare type of heart failure which presents towards the end of pregnancy or in the first 5 months after delivery. Depending on the geographical location the incidence is reported in the literature as 1:300 up to 1:15,000. There are a number of known risk factors, such as multiparity and age of the mother over 30 years. The symptoms of PPCM correspond to those of idiopathic cardiomyopathy. The diagnosis is mainly carried out using echocardiography which shows a clear reduction of systolic left ventricular function. The therapeutic approach is the same as for idiopathic cardiomyopathy and in this context it is absolutely necessary to show caution concerning the state of pregnancy and the resulting contraindications for therapeutic drugs. The prognosis is dependent on recovery from the heart failure during the first 6 months postpartum. The lethality of the disease is high and is given in the literature as up to 28 %. Because of its complexity PPCM is an interdisciplinary challenge. In the peripartum phase a close cooperation between the disciplines of cardiology, cardiac surgery, neonatology, obstetrics and anesthesiology is indispensable. For anesthesiology the most important aspects are the mostly advanced unstable hemodynamic condition of the mother and the planning and implementation of the perioperative management. This article presents the case of a patient in advanced pregnancy with signs of acute severe heart failure and a suspected diagnosis of PPCM. The patient presented as an emergency case and delivery of the child was carried out using peridural anesthesia with a stand-by life support machine.

Topics: Adult; Anesthesia, Conduction; Anesthesia, General; Cardiovascular Agents; Cesarean Section; Electrocardiography; Female; Heart Diseases; Humans; Monitoring, Intraoperative; Perioperative Care; Peripartum Period; Postoperative Care; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis; Risk Factors

To characterize sleeping respiratory rates (SRRs) and resting respiratory rates (RRRs), collected in the home environment, of dogs with subclinical heart disease that could result in left-sided congestive heart failure.. Prospective cross-sectional study.. 190 adult dogs with subclinical left-sided heart disease.. Most dogs had mitral valve disease or dilated cardiomyopathy of various severities. Clients collected ten 1-minute SRRs or RRRs during a period ranging from 1 week to 6 months. Clinicians provided echocardiographic and medical data on each patient.. The within-dog mean SRR (SRRmean; 16 breaths/min) was significantly lower than the within-dog mean RRR (RRRmean; 21 breaths/min). Seven dogs had SRRmean and 33 dogs had RRRmean > 25 breaths/min; 1 dog had SRRmean and 12 dogs had RRRmean > 30 breaths/min; these dogs mostly had a left atrial (LA)-to-aortic ratio > 1.8. Dogs with moderate LA enlargement had a significantly higher SRRmean than did other dogs. However, median SRRmean for each of 4 levels of LA enlargement was < 20 breaths/min; median RRRmean for each of 4 levels of LA enlargement was < 25 breaths/min. Both within-dog SRR and RRR remained stable for 10 consecutive measurements. Treatment with cardiac medications or presence of pulmonary hypertension was not associated with SRRmean or RRRmean.. Results suggested that dogs with confirmed subclinical left-sided heart disease of various severities generally had SRRmean < 25 breaths/min, which was infrequently exceeded at any time, and that SRR and RRR remained stable, regardless of individual within-dog SRRmean or RRRmean.

Topics: Animals; Cardiovascular Agents; Dog Diseases; Dogs; Female; Heart Diseases; Male; Respiratory Physiological Phenomena; Sleep

Patients with chronic kidney disease (CKD) frequently suffer from heart disease as well. The combination of the two processes can exacerbate inflammation, resulting in increases in both resistance to erythropoietin (EPO) and mortality.. The aim of this study was to determine the prevalence of heart disease in a representative group of non-dialysis patients with stage 4-5 CKD, and the influence of that entity on EPO requirements and on mortality during a period of 36 months.. 134 patients (68% on EPO at the beginning, increasing to 72.3% during follow-up) were monitored for 36 months. To evaluate the dose-response effect of EPO therapy, we used the erythropoietin resistance index (ERI) calculated as the weekly weight-adjusted dose of EPO divided by the haemoglobin level. The ERI was determined both initially and during the last six months before the end of the study.. 39 patients (29.1%) had history of heart disease; 22 (16.4%) had suffered from heart failure (HF). The ERI was higher in patients with a history of heart disease or HF and those treated with drugs acting on the renin-angiotensin system (ACE inhibitors or ARBs). Using ERI as the dependent variable in the multivariate analysis, the variables that composed the final model were ferritin, haemoglobin, glomerular filtration rate and history of HF. The 36 month mortality rate (n=39 patients) was higher in the group having ERI above the median (2.6IU/week/kg/gram of haemoglobin in 100ml) (P=.002), and in the groups with heart disease (P=.001) or HF (P=.001) according to the Kaplan-Meier survival analysis.. Patients with history of heart disease or HF have a higher ERI, and all of these characteristics are associated with lower survival. ERI can be considered a marker for risk of death in the short to-medium term.

Topics: Aged; Aged, 80 and over; Anemia; Autoimmune Diseases; Cardio-Renal Syndrome; Cardiovascular Agents; Comorbidity; Cross-Sectional Studies; Dose-Response Relationship, Drug; Drug Resistance; Erythropoietin; Female; Ferritins; Glomerular Filtration Rate; Heart Diseases; Heart Failure; Hemoglobins; Humans; Kaplan-Meier Estimate; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Recombinant Proteins; Severity of Illness Index

Metabolic syndrome (MetS) is a clustering of factors that are associated with increased cardiovascular risk. We aimed to investigate the proportion of patients with MetS in patients undergoing cardiac rehabilitation (CR), and to describe differences between patients with MetS compared to those without MetS with regard to (1) patient characteristics including demographics, risk factors, and comorbidities, (2) risk factor management including drug treatment, and (3) control status of risk factors at entry to CR and discharge from CR.. Post-hoc analysis of data from 27,904 inpatients (Transparency Registry to Objectify Guideline-Oriented Risk Factor Management registry) that underwent a CR period of about 3 weeks were analyzed descriptively in total and compared by their MetS status.. In the total cohort, mean age was 64.3 years, (71.7% male), with no major differences between groups. Patients had been referred after a ST elevation of myocardial infarction event in 41.1% of cases, non-ST elevation of myocardial infarction in 21.8%, or angina pectoris in 16.7%. They had received a percutaneous coronary intervention in 55.1% and bypass surgery (coronary artery bypass graft) in 39.5%. Patients with MetS (n = 15,819) compared to those without MetS (n = 12,085) were less frequently males, and in terms of cardiac interventions, more often received coronary artery bypass surgery. Overall, statin use increased from 79.9% at entry to 95.0% at discharge (MetS: 79.7% to 95.2%). Patients with MetS compared to those without MetS received angiotensin converting enzyme inhibitors, angiotensin receptor blockers, oral antidiabetics, and insulin at entry and discharge more frequently, and less frequently clopidogrel and aspirin/clopidogrel combinations. Mean blood pressure was within the normal range at discharge, and did not differ substantially between groups (124/73 versus 120/72 mmHg). Overall, between entry and discharge, levels of total cholesterol, low density lipoprotein cholesterol, and triglycerides were substantially lowered, in particular in MetS patients. Thus, control rates of lipid parameters improved substantially, with the exception of high density lipoprotein cholesterol. Low density lipoprotein cholesterol rates <100 mg/dL increased from 38.7% at entry to 73.8% at discharge (MetS: from 39.4% to 74.6%) and triglycerides control rates (<150 mg/dL) from 58.1% to 70.4% (MetS: 43.7% to 62.2%). Physical fitness on exercise testing improved substantially in both groups.. Patients with and without MetS benefited substantially from the participation in CR, as their lipid profile, blood pressure, and physical fitness improved. Treatment effects were similar in the two groups.

Topics: Aged; Angioplasty, Balloon, Coronary; Blood Glucose; Blood Pressure; Cardiovascular Agents; Chi-Square Distribution; Comorbidity; Coronary Artery Bypass; Drug Therapy, Combination; Drug Utilization; Female; Germany; Guideline Adherence; Heart Diseases; Humans; Inpatients; Lipids; Male; Metabolic Syndrome; Middle Aged; Practice Guidelines as Topic; Practice Patterns, Physicians'; Preventive Health Services; Prospective Studies; Registries; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

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

Topics: Blood Coagulation; Cardiovascular Agents; Drug Design; Heart Diseases; Humans

In women with cardiac disease physiological changes in the cardiovascular system associated with pregnancy may precipitate decompensation. Heart disease is the commonest cause of maternal death. Close multidisciplinary working is important to ensure the best care possible for pregnant women with heart disease.

Topics: Breast Feeding; Cardiovascular Agents; Female; Heart Diseases; Humans; Preconception Care; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Care

Cardiac rehabilitation programs develop in accordance with guidelines, but also in response to local needs and resources. This study evaluated features of Ontario cardiac rehabilitation programs in accordance with guidelines, emerging evidence and treating underserved populations.. In this cross-sectional study, all Ontario cardiac rehabilitation programs were mailed an investigator-generated survey. Responses were received from 38 of 45 (84.4%) programs.. Twenty-seven (71.1%) cardiac rehabilitation programs were located within a hospital. Twenty-four (63.2%) programs reported that they offer two sessions of exercise and education per week. Twenty-six (68.4%) programs offered an alternative model of program delivery other than on-site, with 10 (27.0%) programs reporting they tailored their programs to rural patients. Twenty-three (62.2%) programs provided services to patients with a noncardiac primary indication. Twenty-six (68.4%) programs systematically screened patients for depressive symptoms. Twenty-seven (71.1%) offered resources to patients postgraduation.. Most cardiac rehabilitation programs offered alternative models of care, such as home-based rehabilitation. Cardiac rehabilitation sites are well integrated within their community, enabling smooth postcardiac rehabilitation transitions for patients. Cardiac rehabilitation programs continue to offer proven comprehensive components, while simultaneously attempting to adapt to meet the needs of patients with other chronic diseases.

Topics: Cardiology Service, Hospital; Cardiovascular Agents; Community Health Services; Comorbidity; Cross-Sectional Studies; Delivery of Health Care, Integrated; Depression; Exercise Therapy; Guideline Adherence; Health Care Rationing; Health Care Surveys; Health Knowledge, Attitudes, Practice; Health Services Accessibility; Health Services Needs and Demand; Heart Diseases; Home Care Services, Hospital-Based; Humans; Models, Organizational; Ontario; Patient Education as Topic; Practice Guidelines as Topic; Risk Factors; Rural Health Services; Surveys and Questionnaires; Vulnerable Populations

Topics: Adolescent; Adult; alpha-Galactosidase; Cardiovascular Agents; Child; Contraindications; Delayed Diagnosis; Diagnosis, Differential; Disease Management; Enzyme Replacement Therapy; Fabry Disease; Female; Heart Diseases; Humans; Incidence; Infant, Newborn; Kidney Failure, Chronic; Leukocytes; Lysosomes; Male; Neuralgia; Renal Replacement Therapy

Cardiovascular disease death rates are higher among Australians from regional and remote areas than those from major cities.. To investigate the causes of excess mortality from heart disease in rural compared to urban Australian women aged over 75 years..   In 2004, 944 older urban and rural participants in the Australian Longitudinal Study on Women's Health aged 77-83 years with self-reported ischaemic heart disease (IHD), heart failure or atrial fibrillation took part in a nested cross-sectional substudy. We used clinical guidelines to determine key management issues for these conditions. Using logistic regression we calculated odds ratios (OR) and 95% confidence intervals (CI) to assess the relationship between management and area of residence.. These older Australian women often did not receive recommended management for their heart conditions. Only 30% reported having had an echocardiogram. Reported use of statins and beta-blockers was low among women with IHD (58% and 41% respectively) and only 32% of women reporting heart failure were taking angiotensin-converting enzyme inhibitors. Women from regional/remote areas had greater odds of reporting never having seen a cardiologist (OR = 3.88, 95% CI 1.72-8.72) and never having had an echocardiogram than women from major cities (OR = 2.86, 95% CI 1.42-5.75). Medication use was similar for rural and urban women.. Our results suggest that best-practice treatments for heart conditions are suboptimally provided to older women. In addition, they suggest differential use of some health services, which might help explain higher cardiovascular mortality among rural compared with urban women.

Topics: Aged; Aged, 80 and over; Australia; Cardiology; Cardiovascular Agents; Comorbidity; Disease Management; Drug Utilization; Echocardiography; Female; Guideline Adherence; Health Services Accessibility; Health Surveys; Heart Diseases; Humans; Office Visits; Practice Guidelines as Topic; Referral and Consultation; Rural Population; Self Report; Socioeconomic Factors; Urban Population

Topics: Cardiac Glycosides; Cardiovascular Agents; Diagnostic Techniques, Cardiovascular; Heart Diseases; History, 20th Century; Humans; Phytotherapy; Switzerland

An ageing population and the extension of indications will in all probability result in an increasing number of cardiac device implantations.. Patients implanted in 2008 and 2009 were identified by means of the French National Hospital Discharge database to establish the implantation rate and the National Health Insurance (NHI) Information System database for patient profiles (76% of the population).. Of the 64,306 pacemaker implantations (1003.7 per million inhabitants [pmi]) in 2009, 21.4% were single chamber, 75.4% double chamber and 3.2% triple chamber (CRT-P). Of the 9028 cardioverter-defibrillator implantations (140.8 pmi) in 2009, 30.1% were single chamber, 27.5% double chamber and 42.5% triple chamber (CRT-D), accounting for 65% of cardiac resynchronization therapy (CRT) implants. Among NHI beneficiaries, 58.6% of cardioverter-defibrillators were implanted for primary prevention. Between 2008 and 2009, CRT-P implantations increased by 8.8% and CRT-D implantations by 29.3%. Regional variations in implantation rates were observed regarding single-chamber pacemakers (15-33%) and CRT-D among CRT (46.2-73.8%). Pacemaker implantations cost €158.4 million overall, 4.5% of which was for CRT-P; cardioverter-defibrillator implantations cost €96 million, 49% of which was for CRT-D. For NHI beneficiaries, 11.9% of CRT-P patients and 6.5% of CRT-D patients already had a device of the same type implanted in the 3 preceding years.. The results confirm the increase in cardioverter-defibrillator implantations in France. The implantation rate remains lower than that in the USA but falls within the European average. Reasons behind significant regional variations in implantation rates need further study.

Topics: Aged; Aged, 80 and over; Cardiac Pacing, Artificial; Cardiovascular Agents; Chi-Square Distribution; Cost-Benefit Analysis; Databases as Topic; Defibrillators, Implantable; Electric Countershock; Equipment Design; Female; France; Health Care Costs; Healthcare Disparities; Heart Diseases; Humans; Male; Middle Aged; National Health Programs; Pacemaker, Artificial; Practice Patterns, Physicians'; Preventive Health Services; Prosthesis Design; Residence Characteristics; Time Factors

The pacemaker channel isoforms are encoded by the hyperpolarization-activated and cyclic nucleotide-gated (HCN) gene family and are responsible for diverse cellular functions including regulation of spontaneous activity in sino-atrial node cells and control of excitability in different types of neurons. Four channel isoforms exist (HCN1-HCN4). The hyperpolarization-activated cardiac pacemaker current (I(f)) has an important role in the generation of the diastolic depolarization in the sino-atrial node, while its neuronal equivalent (I(h)) is an important contributor to determination of resting membrane potential, and plays an important role in neuronal functions such as synaptic transmission, motor learning and generation of thalamic rhythms. Ivabradine is a novel, heart rate-lowering drug which inhibits the pacemaker (I(f)) current in the heart with high selectivity and with minimal effect on haemodynamic parameters. Ivabradine is beneficial in patients with chronic stable angina pectoris equally to beta receptor blocker and calcium channel antagonist drugs. There is increasing interest to apply this drug in other fields of cardiology such as heart failure, myocardial infarction, cardiac arrhyhtmias. Heart rate reduction might improve clinical outcomes in heart failure. HCN upregulation presumably contributes to increased (I(f)) and may play a role in ventricular and atrial arrhythmogenesis in heart failure. In the nervous system the HCN channels received attention in the research areas of neuropathic pain, epilepsy and understanding the mechanism of action of volatile anaesthetics. This article delineates that the pharmacological modulation of cardiac and neuronal HCN channels can serve current or future drug therapy and introduces some recently investigated HCN channel inhibitor compounds being potential candidates for development.

Topics: Benzazepines; Cardiovascular Agents; Clinical Trials as Topic; Cyclic Nucleotide-Gated Cation Channels; Heart Diseases; Heart Rate; Humans; Ivabradine; Protein Isoforms; Sinoatrial Node

Topics: Abortion, Induced; Aortic Diseases; Cardiovascular Agents; Contraindications; Counseling; Female; Heart Diseases; Humans; Hypertension; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Complications, Infectious; Prenatal Care; Prenatal Diagnosis; Venous Thromboembolism

Topics: Cardiology; Cardiovascular Agents; Elective Surgical Procedures; Europe; Heart Diseases; Heart Function Tests; Humans; Perioperative Care; Peripheral Vascular Diseases; Practice Guidelines as Topic; Risk Assessment; Societies, Medical; Vascular Surgical Procedures

Our aim was to access the incidence of late major adverse cardiac events (MACE) and stent thrombosis (ST) in nonselected, complex patients followed for a period >/=4 years.. Despite the efficacy of drug-eluting stents (DES) in reducing repeated target lesion revascularization, concerns regarding the occurrence of late and very late ST have partially obscured the benefits of this novel technology.. All consecutive patients treated solely with DES between May 2002 and January 2005 were enrolled into this prospective, nonrandomized, single-center registry. The primary end point was long-term occurrence of MACE up to 7 years. Independent predictors of MACE, cardiac death, target lesion revascularization, and ST were obtained by a multivariate Cox proportional hazards regression model.. A total of 1,010 patients were enrolled. Most of them were men (77%) with a mean age of 63.7 years. Stent/patient rate was 1.4. Patients were kept in dual antiplatelet therapy for 3 and 6 months after Cypher (Cordis, Johnson & Johnson, Miami Lakes, Florida) and Taxus (Boston Scientific Corp., Natick, Massachusetts) stent implantation, respectively. Follow-up was obtained in 98.2% of the cohort (median 5.01 years). Survival free of MACE and cumulative incidence of definite/probable ST were 84.6% and 1.7%, respectively. Independent predictors of ST were percutaneous coronary intervention in the setting of acute myocardial infarction, DES overlapping, treatment of multivessel disease, presence of moderate-to-severe calcification at lesion site, and in-stent residual stenosis.. The deployment of DES in complex, real-world patients resulted in a low rate of very long-term MACE and ST. However, ST still occurs very long after the index procedure.

Topics: Aged; Angioplasty, Balloon, Coronary; Brazil; Calcinosis; Cardiovascular Agents; Coronary Restenosis; Disease-Free Survival; Drug Therapy, Combination; Drug-Eluting Stents; Female; Heart Diseases; Humans; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Platelet Aggregation Inhibitors; Proportional Hazards Models; Prospective Studies; Registries; Risk Assessment; Risk Factors; Sirolimus; Thrombosis; Time Factors; Treatment Outcome

Growing evidence suggests that arginase misregulation plays a key role in the pathophysiology of essential hypertension. In the present study, we investigated the potential cardiovascular therapeutic effects of a long-term treatment with an arginase inhibitor in adult spontaneously hypertensive rats (SHR) with fully developed hypertension.. Treatment of 25-week-old SHR with the arginase inhibitor N(omega)-hydroxy-nor-L-arginine (nor-NOHA, 40 mg/day for 10 weeks) sustainably reduced systolic blood pressure (-30 mmHg, P < 0.05). The antihypertensive effect of nor-NOHA was associated with changes on mesenteric artery reactivity including the restoration of angiotensin-II-induced contraction and acetylcholine-induced vasodilation to the values of normotensive Wistar Kyoto rats. Both nitric oxide synthase and cyclooxygenase-dependent mechanisms account for the improvement of endothelial function afforded by the arginase inhibitor, which in addition blunted hypertension-induced endothelial arginase I overexpression in mesenteric arteries. Nor-NOHA also prevented the remodelling of aorta as measured by collagen content and media/lumen ratio, and improved the compliance of carotid artery in SHR. Cardiac fibrosis assessed by collagen content of left heart ventricle was reduced by nor-NOHA, with no significant effect on cardiac hypertrophy.. Our results report that a long-term treatment with an arginase inhibitor reduced blood pressure, improved vascular function, and reduced cardiac fibrosis in SHR with fully developed hypertension. These data suggest that arginase represents a promising novel target for pharmacological intervention in essential hypertension.

Topics: Animals; Aorta; Arginase; Arginine; Blood Pressure; Cardiovascular Agents; Carotid Arteries; Collagen; Compliance; Cyclooxygenase 1; Cyclooxygenase 2; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelium, Vascular; Enzyme Inhibitors; Fibrosis; Heart Diseases; Hypertension; Male; Membrane Proteins; Mesenteric Arteries; Myocardium; Nitric Oxide Synthase; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Time Factors; Vasoconstriction; Vasoconstrictor Agents; Vasodilation; Vasodilator Agents

Peripheral vascular disease (PVD) is associated with a high risk of cardiovascular events after an acute coronary syndrome (ACS). The impact of suboptimal risk-factor control and drug prescription on morbidity and mortality rates in patients with PVD following an ACS remains to be established.. To assess whether a global atherosclerosis management programme and optimal secondary prevention could benefit high-risk PVD patients after an ACS.. A total of 851 ACS patients underwent an intensified intervention focusing on evaluating risk factors and atherosclerosis lesions, and on optimizing treatment and education. We compared its impact on long-term risk factors, medication observance and cardiovascular outcomes in patients with coronary artery disease (CAD) alone (n=715, 84.0%) and with both CAD and PVD (n=136).. At a median follow-up of 18.6months, both groups reached recommended secondary prevention goals and showed no significant differences in rates of drug prescription. PVD was not associated with minor cardiovascular events (hazard ratio [HR] 1.32, 95% confidence interval [CI] 0.57-3.02) but remained independently associated with major (HR 2.15, 95% CI 1.12-4.13) and total (HR 1.76, 95% CI 1.05-2.93) cardiovascular events. Compared to patients with CAD alone, this risk was significantly higher in CAD patients with both PVD and diabetes (HR 2.87, 95% CI 1.52-5.43), but not in PVD patients without diabetes (HR 1.35, 95% CI 0.71-2.56) or diabetic patients without PVD (HR 1.11, 95% CI 0.68-1.81).. Despite optimization of risk-factor control and drug prescription after ACS, patients with both PVD and diabetes carry a 2.9-fold higher risk of cardiovascular events at 18-month follow-up versus patients with CAD alone. This excess risk was not significant in PVD patients without diabetes or in diabetic patients without PVD.

Topics: Acute Coronary Syndrome; Aged; Cardiovascular Agents; Chi-Square Distribution; Diabetes Complications; Drug Prescriptions; Female; Health Knowledge, Attitudes, Practice; Heart Diseases; Humans; Male; Medication Adherence; Middle Aged; Patient Education as Topic; Peripheral Vascular Diseases; Proportional Hazards Models; Risk Assessment; Risk Factors; Secondary Prevention; Time Factors; Treatment Outcome

This study aimed to evaluate the impact of angiographic and intravascular ultrasound (IVUS) features on clinical outcome in nondiabetic and type 2 diabetic patients after percutaneous coronary intervention (PCI) with sirolimus-eluting stent (SES) implantation.. Repeat coronary angiography with IVUS imaging was performed after SES-based PCI for de-novo lesions in 128 diabetic and 327 nondiabetic patients (189 lesions and 504 lesions, respectively). The rate of major adverse cardiac events including cardiac death, non fatal myocardial infarction (MI), and target lesion revascularization during clinical follow-up was recorded.. In-stent and in-segment late loss, intimal hyperplasia volume, and percentage volumetric obstruction were similar, but stented external elastic membrane cross-sectional area and reference/stented segment ratio were lower in diabetic than in nondiabetic patients. Incomplete stent apposition (ISA) was less frequent, but occurrence of new coronary lesions was higher in diabetic than in nondiabetic patients. Despite similar target lesion revascularization, cumulative survival rates freedom from composite cardiac death and nonfatal MI or major adverse cardiac events were reduced in diabetic patients. Cox proportional hazards model identified diabetes, left ventricular ejection fraction, minimal stent CSA, maximal ISA area, atherosclerotic progression and lesion length as independent predictors of non fatal MI or mortality at follow-up.. In diabetic patients, PCI with SES implantation neutralizes the excess risk of intimal hyperplasia and decreases occurrence of ISA, but could not modify the propensity of increased adverse clinical outcomes at follow-up.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Coronary Vessels; Diabetes Mellitus, Type 2; Drug-Eluting Stents; Female; Heart Diseases; Humans; Hyperplasia; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Predictive Value of Tests; Proportional Hazards Models; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Treatment Outcome; Ultrasonography, Interventional

Topics: Animals; Cardiovascular Agents; Dog Diseases; Dogs; Electrocardiography, Ambulatory; Heart Diseases; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests

Cardiotoxicity is frequently present with anthracycline treatment. Most acute myeloid leukemia (AML) protocols use anthracyclines. Dexrazoxane has cardioprotective activity. The aim of this study was to evaluate cardioprotection of dexrazoxane in a prospective study. Fifty pediatric AML patients were treated with a Medical Research Council AML 10 modified protocol with dexrazoxane previous to any anthracycline dose. Cardiac function was evaluated at diagnosis, before every cycle, and every 6 months after the end of chemotherapy. Accumulative doses of anthracycline reached 424 mg/m (150 to 850 mg/m). Forty-eight patients (96%) received a dose higher than 300 mg/m. Twenty-eight percent had a grade of cardiotoxicity (24% grade 1 and 4% grade 2). Non 3 or 4 grade cardiotoxicity was seen. Cumulated anthracycline doses did not correlated with cardiotoxicity (P=0.815). The event-free survival was 53%, 15.7% died of disease, and 11.8% died free of leukemia. There is still not an agreement for the optimal method to reduce cardiotoxicity in children receiving anthracyclines. In our study, we could conclude that the use of dexrazoxane was effective cardioprotectant to allow a high-dose of anthracycline therapy. A randomized study is necessary to consolidate this asseveration.

Topics: Adolescent; Anthracyclines; Cardiovascular Agents; Child; Child, Preschool; Female; Follow-Up Studies; Heart Diseases; Humans; Infant; Leukemia, Myeloid, Acute; Male; Prospective Studies; Razoxane; Survival Rate; Treatment Outcome

The aim of this study was to determine which drug-eluting stent (DES) is preferable for the treatment of ST-segment elevation myocardial infarction (STEMI) and to elucidate the impact of diabetes mellitus on the outcome of each DES.. Recent studies have shown the benefit of DES in patients with STEMI. Diabetes mellitus might differentially affect outcomes of each DES.. We analyzed the large-scale, prospective, observational KAMIR (Korea Acute Myocardial Infarction Registry) study, which enrolled 4,416 STEMI patients (26% with diabetes) treated with paclitaxel-eluting stent (PES) or sirolimus-eluting stent (SES). Primary outcome was major adverse cardiac event (MACE), defined as a composite of mortality, nonfatal myocardial infarction, and target lesion revascularization (TLR).. In the overall population, the MACE rate at 1 year was significantly higher in the PES than the SES group (11.6% vs. 8.6%, p = 0.014), which was mainly due to increased TLR (3.7% vs. 1.8%, p < 0.001). In the diabetic subgroup, however, the MACE rate was not significantly different between PES and SES (14.5% vs. 12.3%, p = 0.217), in contrast to the nondiabetic subgroup, where PES was inferior to SES as in the overall population. Matching by propensity-score did not significantly alter these results. For TLR, there was interaction between the type of stents and diabetes mellitus (unadjusted: p = 0.052; after propensity-score matching: p = 0.035).. The PES was inferior to the SES in the overall population, with regard to the occurrence of MACE and TLR. However, subgroup analysis for diabetic subjects showed no differences in clinical outcomes between PES and SES. These results suggest that diabetes differentially affects the outcome of first-generation DES.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Chi-Square Distribution; Diabetes Complications; Drug-Eluting Stents; Female; Heart Diseases; Humans; Korea; Male; Middle Aged; Myocardial Infarction; Paclitaxel; Propensity Score; Proportional Hazards Models; Prospective Studies; Prosthesis Design; Recurrence; Registries; Risk Assessment; Risk Factors; Sirolimus; Time Factors; Treatment Outcome

Doxorubicin may cause a rare but serious cardiotoxicity. Dexrazoxane is a cardioprotectant drug used to reduce the risk of cardiotoxicity in human patients. In this study, 25 tumour-bearing dogs were treated with concurrent doxorubicin and dexrazoxane. The total number of doses of dexrazoxane given was 54 (range 1-5 doses per dog, median 2 doses). Five dogs received more than 165 mg m(2) cumulative doxorubicin dose before starting dexrazoxane. Haematologic, gastrointestinal and cardiovascular toxicities were considered tolerable. The combination of doxorubicin with dexrazoxane was well tolerated with minimal side-effects in this patient cohort. Future studies are required to evaluate potential cardioprotective effects of dexrazoxane given concurrently with doxorubicin.

Topics: Animals; Cardiovascular Agents; Dog Diseases; Dogs; Doxorubicin; Drug Therapy, Combination; Gastrointestinal Diseases; Heart Diseases; Neoplasms; Razoxane

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Cardiovascular Agents; Child; Doxorubicin; Female; Heart Diseases; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Randomized Controlled Trials as Topic; Razoxane; Sex Characteristics

Topics: Animals; Biomarkers; Cardiovascular Agents; Heart Diseases; Humans; Myocardial Contraction; Myocardium

Herein, we describe the case of a 50-year-old man who had a fistula, located between the left anterior descending coronary artery and the left ventricle, that caused myocardial infarction. Electrocardiography revealed a loss of R-wave progression in leads V(1) through V(4), and transthoracic echocardiography showed an apical aneurysm. Selective coronary angiography was performed. Dimensions of the left anterior descending coronary artery, and digital caliper measurements of stenosis within, were normal. After the injection of angiographic contrast material from the distal part of the left anterior descending coronary artery, a smoky, opaque accumulation colored the left ventricle. The digital caliper measurement of the left anterior descending coronary artery was again found to be normal. In the apex of the left ventricle, ventriculography in the left anterior oblique position revealed a small aneurysm, and a myocardial perfusion scan showed a fixed perfusion defect.Cases of coronary fistulae that result in myocardial infarction are rare. Because the patient had no ongoing symptoms after his myocardial infarction, medical therapy was prescribed.

Topics: Cardiovascular Agents; Coronary Angiography; Coronary Vessel Anomalies; Echocardiography; Electrocardiography; Heart Diseases; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Infarction; Vascular Fistula

In addition to their central role in ATP synthesis, mitochondria play a critical role in cell death. Oxidative stress accompanied by calcium overload, ATP depletion, and elevated phosphate levels induces mitochondrial permeability transition (MPT) with formation of nonspecific MPT pores (MPTP) in the inner mitochondrial membrane. Pore opening results in mitochondrial dysfunction with uncoupled oxidative phosphorylation and ATP hydrolysis, ultimately leading to cell death. For the past 20 years, three proteins have been accepted as key structural components of the MPTP: adenine nucleotide translocase (ANT) in the inner membrane, cyclophilin D (CyP-D) in the matrix, and the voltage-dependent anion channel (VDAC) in the outer membrane. However, most recent studies have questioned the molecular identity of the pores. Genetic studies have eliminated the VDAC as an essential component of MPTP and attributed a regulatory (rather than structural) role to ANT. Currently, the phosphate carrier appears to play a crucial role in MPTP formation. MPTP opening has been examined extensively in cardiac pathological conditions, including ischemia/reperfusion as well as heart failure. Accordingly, MPTP is accepted as a therapeutic target for both pharmacological and conditional strategies to block pore formation by direct interaction with MPTP components or indirectly by decreasing MPTP inducers. Inhibition of MPTP opening by reduction of CyP-D activity by nonimmunosuppressive analogs of cyclosporine A or sanglifehrin A, as well as attenuation of reactive oxygen species accumulation through mitochondria-targeted antioxidants, is the most promising. This review outlines our current knowledge of the structure and function of the MPTP and describes possible approaches for cardioprotection.

Topics: Animals; Cardiovascular Agents; Heart Diseases; Heart Failure; Humans; Mitochondria; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Reperfusion Injury

In October 2008, in a public forum organized by the Cardiac Safety Research Consortium and the Health and Environmental Sciences Institute, leaders from government, the pharmaceutical industry, and academia convened in Bethesda, MD, to discuss current challenges in evaluation of short- and long-term cardiovascular safety during drug development. The current paradigm for premarket evaluation of cardiac safety begins with preclinical animal modeling and progresses to clinical biomarker or biosignature assays. Preclinical evaluations have clear limitations but provide an important opportunity to identify safety hazards before administration of potential new drugs to human subjects. Discussants highlighted the need to identify, develop, and validate serum and electrocardiogram biomarkers indicative of early drug-induced myocardial toxicity and proarrhythmia. Specifically, experts identified a need to build consensus regarding the use and interpretation of troponin assays in preclinical evaluation of myocardial toxicity. With respect to proarrhythmia, the panel emphasized a need for better qualitative and quantitative biomarkers for arrhythmogenicity, including more streamlined human thorough QT study designs and a universal definition of the end of the T wave. Toward many of these ends, large shared data repositories and a more seamless integration of preclinical and clinical testing could facilitate the development of novel approaches to both cardiac safety biosignatures. In addition, more thorough and efficient early clinical studies could enable better estimates of cardiovascular risk and better inform phase II and phase III trial design. Participants also emphasized the importance of establishing formal guidelines for data standards and transparency in postmarketing surveillance. Priority pursuit of these consensus-based directions should facilitate both safer drugs and accelerated access to new drugs, as concomitant public health benefits.

Topics: Arrhythmias, Cardiac; Biomarkers; Cardiovascular Agents; Cardiovascular Diseases; Critical Pathways; Drug Evaluation; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Heart Diseases; Humans; Research; Risk Management; Safety; Technology Transfer; Troponin

Topics: Algorithms; Biomarkers; Cardiovascular Agents; Diagnostic Techniques, Cardiovascular; Exercise Tolerance; Heart Diseases; Humans; Hypertension, Pulmonary; Hypoxia; Lung Transplantation; Prognosis; Pulmonary Veno-Occlusive Disease; Referral and Consultation; Risk Factors; Terminal Care; Thromboembolism

Topics: Adult; Aged; Anesthesia; Biomarkers; Blood Glucose; Cardiac Catheterization; Cardiovascular Agents; Cerebrovascular Disorders; Coronary Angiography; Echocardiography; Electric Countershock; Electrocardiography; Heart Diseases; Humans; Intraoperative Complications; Lung Diseases; Middle Aged; Myocardial Revascularization; Pain, Postoperative; Preoperative Care; Risk Assessment; Young Adult

Neuregulin-1 (NRG1) is a potential therapeutic agent for the treatment of doxorubicin (Dox)-induced heart failure. NRG1, however, activates the erbB2 receptor, which is frequently overexpressed in breast cancers. It is, therefore, important to understand how NRG1, via erbB2, protects the heart against Dox cardiotoxicity. Here, we studied NRG1-erbB2 signaling in Dox-treated mice hearts and in isolated neonatal rat ventricular myocytes (NRVM). Male C57BL/6 mice were treated with recombinant NRG1 before and daily after a single dose of Dox. Cardiac function was determined by catheterization. Two-week survival was analyzed by the Kaplan-Meier method. Cardiac troponins [cardiac troponin I (cTnI) and cardiac troponin T (cTnT)] and phosphorylated Akt protein levels were determined in mice hearts and in NRVM by Western blot analysis. Activation of caspases and ubiquitinylation of troponins were determined in NRVM by caspase assay and immunoprecipitation. NRG1 significantly improved survival and cardiac function in Dox-treated mice. NRG1 reduced the decrease in cTnI, cTnT, and cardiac troponin C (cTnC) and maintained Akt phosphorylation in Dox-treated mice hearts. NRG1 reduced the decrease in cTnI and cTnT mRNA and proteins in Dox-treated NRVM. Inhibition of erbB2, phosphoinositide 3-kinase (PI3K), Akt, and mTOR blocked the protective effects of NRG1 on cTnI and cTnT in NRVM. NRG1 significantly reduced Dox-induced caspase activation, which degraded troponins, in NRVM. NRG1 reduced Dox-induced proteasome degradation of cTnI. NRG1 attenuates Dox-induced decrease in cardiac troponins by increasing transcription and translation and by inhibiting caspase activation and proteasome degradation of troponin proteins. NRG1 maintains cardiac troponins by the erbB2-PI3K pathway, which may lessen Dox-induced cardiac dysfunction.

Topics: Animals; Animals, Newborn; Antibiotics, Antineoplastic; Biomarkers; Cardiovascular Agents; Caspases; Cells, Cultured; Creatine Kinase; Disease Models, Animal; Doxorubicin; Glycoproteins; Heart Diseases; Humans; Injections, Subcutaneous; Intracellular Signaling Peptides and Proteins; Male; Mice; Mice, Inbred C57BL; Myocardium; Neuregulin-1; Phosphatidylinositol 3-Kinases; Phosphorylation; Proteasome Endopeptidase Complex; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Wistar; Receptor, ErbB-2; Recombinant Proteins; Signal Transduction; Time Factors; TOR Serine-Threonine Kinases; Transcription, Genetic; Troponin I; Troponin T; Ubiquitination; Up-Regulation; Ventricular Function, Left

To investigate the incidence of atrial fibrillation after successful radiofrequency ablation for typical atrial flutter (AFL) and to compare its incidence with that of a reference population from the Framingham Heart Study to determine whether atrial flutter is an independent predictor for development of atrial fibrillation.. Medical records of 234 patients who underwent radiofrequency ablation for AFL between January 1, 2002, and June 30, 2006, were reviewed. Patients were excluded if they had a history of atrial fibrillation or sustained atrial arrhythmia other than AFL or if they had atrial tachyarrhythmias other than AFL that could be induced during electrophysiology study (133 total patients excluded). The remaining 101 patients who underwent successful radiofrequency ablation for AFL were monitored for new-onset atrial fibrillation.. During the mean+/-SD follow-up period of 574+/-315 days, atrial fibrillation developed in 13 (12.9%) of 101 patients. Atrial fibrillation developed in 12 of these patients within 6 months of ablation. The cumulative event-free rates (95% confidence intervals) were 97% (94%-100%) at 1 month, 91% (87%-97%) at 3 months, and 86% (81%-94%) at 6 months. Compared with the general population, patients aged 50 to 79 years who had ablation had a significantly higher incidence of atrial fibrillation (50-59 years, P=.01; 60-69 years, P=.001; 70-79 years, P=.007).. Our finding of atrial fibrillation in 12.9% of patients whose atrial flutter was successfully eradicated suggests that patients with atrial flutter are at increased risk of developing atrial fibrillation, especially within the first 6 months after ablation.

Topics: Aged; Atrial Fibrillation; Atrial Flutter; Cardiovascular Agents; Catheter Ablation; Electrophysiology; Female; Heart Diseases; Humans; Kaplan-Meier Estimate; Male; Medical Records; Middle Aged; Risk Factors; Ultrasonography

The objective of this study was to investigate whether a cytoprotective herb-derived agent, Ginkgo biloba extract (EGb) 761, could have a beneficial effect on doxorubicin-induced cardiac toxicity in vitro and in vivo.. Primary cultured neonatal rat cardiomyocytes were treated with the vehicle, doxorubicin (1 microM), EGb761 (25 microg/mL), or EGb761 plus doxorubicin. After 24 h, doxorubicin upregulated p53 mRNA expression, disturbed Bcl-2 family protein balance, disrupted mitochondrial membrane potential, precipitated mitochondrion-dependent apoptotic signalling, induced apoptotic cell death, and reduced viability of cardiomyocytes, whereas EGb761 pretreatment suppressed all the actions of doxorubicin. Similarly, rats treated with doxorubicin [3 mg/kg intraperitoneally (i.p.) three doses every other day] displayed retarded growth of body and heart as well as elevated apoptotic indexes in heart tissue at both 7 and 28 days after exposure, whereas EGb761 pretreatment (5 mg/kg i.p. 1 day before each dose of doxorubicin) effectively neutralized the aforementioned gross and cellular adverse effects of doxorubicin.. Doxorubicin impairs viability of cardiomyocytes at least partially by activating the p53-mediated, mitochondrion-dependent apoptotic signalling. EGb761 can effectively and extensively counteract this action of doxorubicin, and may potentially protect the heart from the severe toxicity of doxorubicin.

Topics: Animals; Animals, Newborn; Apoptosis; Cardiovascular Agents; Caspase 3; Cell Survival; Cells, Cultured; Cytochromes c; Cytoprotection; Disease Models, Animal; Doxorubicin; Ginkgo biloba; Heart Diseases; Male; Membrane Potential, Mitochondrial; Mitochondria, Heart; Myocytes, Cardiac; Plant Extracts; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Time Factors; Tumor Suppressor Protein p53

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Bypass; Coronary Artery Disease; Echocardiography; Elective Surgical Procedures; Heart Diseases; Humans; Myocardial Infarction; Patient Selection; Practice Guidelines as Topic; Preoperative Care; Randomized Controlled Trials as Topic; Research Design; Risk Assessment; Risk Factors; Severity of Illness Index; Treatment Outcome; Vascular Surgical Procedures

Topics: Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Artery Bypass; Coronary Artery Disease; Echocardiography; Elective Surgical Procedures; Heart Diseases; Humans; Patient Selection; Practice Guidelines as Topic; Preoperative Care; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Severity of Illness Index; Treatment Outcome; Vascular Surgical Procedures

Cardiovascular disease is an important cause of morbidity and death in kidney transplant recipients. This study examines the Framingham risk score's ability to predict cardiac and stroke events. Because cyclosporine and tacrolimus have different cardiovascular risk profiles, these agents were also examined.. A prospective cohort evaluation of 540 patients were followed for a median of 4.7 yr in an outpatient kidney transplant clinic. Baseline Framingham risk scores were calculated and all cardiovascular outcomes were collected.. Rates per 100 patient-years were 1.79 for cardiac and 0.78 for stroke events. The ratio of observed-to-predicted cardiac events was 1.64-fold higher [95% confidence interval (CI) 1.19 to 2.94] for the cohort, 2.74-fold higher (95% CI 1.70 to 4.24) in patients age 45 to 60 with prior cardiac disease or diabetes mellitus, but not higher in other age subgroups. Stroke was not increased above predicted. Risk scores for cardiac (c = 0.65, P = 0.003) and stroke (c = 0.71, P = 0.004) events were modest predictors. 10-yr event scores for cardiac (9.3 versus 13.5%, P < 0.001) and stroke (7.1 versus 10.0%, P = 0.002) were lower for tacrolimus compared with cyclosporine-treated patients. However observed cardiac events were higher in tacrolimus recipients (2.50, 95% CI 1.09 to 5.90) in an adjusted Cox model.. Although risk scores are only modest predictors, patients with the highest event rates are easily identified. Treating high-risk patients with cardioprotective medications should remain a priority.

Topics: Adult; Age Factors; Aged; Ambulatory Care Facilities; Cardiovascular Agents; Cyclosporine; Diabetes Complications; Disease-Free Survival; Female; Health Status Indicators; Heart Diseases; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Stroke; Tacrolimus; Time Factors

To describe spontaneously reported cases of torsades de pointes (TdP) in Sweden and to investigate if this adverse drug reaction (ADR) was labelled in the summary of product characteristics (SPC) for the drugs implicated.. Reported cases of TdP 1991-2006 were identified and evaluated with regard to drug use and other possible risk factor.. Among a total of 61 788 ADRs, 88 cases of TdP were identified. In these cases, 27 different suspected drugs were implicated. Cardiac drugs were involved in most reports (74%; 65/88), with sotalol being the most frequently suspected drug (57%, 58/88). In addition to drug treatment two or more established risk factors were present in 85% of the cases (75/88). Heart disease (90%; 79/88) was the most common risk factor followed by age over 65 years (72%; 63/88) and female gender (70%; 62/88). TdP or QT prolongation were labelled in the SPC for 33% (9/27) of the drugs implicated in the 88 cases. However, supporting evidence for an association was found elsewhere in 56% (15/27) for the different drugs implicated in the reports. Although citalopram was the third most common suspected drug in the reports (10%; 9/88), TdP was not listed in the SPC.. TdP is a rarely reported ADR. Several risk factors are often present. In two thirds of the drugs implicated in the reports neither TdP nor QT prolongation was labelled in the SPC. Further investigations are needed regarding the association between citalopram and TdP.

Topics: Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Age Factors; Aged; Aged, 80 and over; Cardiovascular Agents; Citalopram; Databases, Factual; Drug Labeling; Female; Heart Diseases; Humans; Long QT Syndrome; Male; Middle Aged; Risk Factors; Sex Factors; Sotalol; Sweden; Torsades de Pointes

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

The enhanced myocardial collagen content, collagen glycation and the resulting advanced glycation end products (AGE) which exhibit the characteristics of increased cross-linking are proposed for the stiffness of myocardium in diabetes. To explore the cardioprotective effect of green tea in diabetes, we study the effect of green tea extract on myocardial collagen characteristics in streptozotocin diabetic rats. The effect of green tea on marker enzymes in serum and cardiac tissues were also assayed to understand the extent of protection. Six weeks after the diabetes induction, diabetic rats were treated with green tea extract [300 mg (kg body weight)(-1)day(-1)] for 4 weeks. AGE were determined by fluorescence assay and cross-linking of collagen by solubility measurement while collagen content was measured by biochemical assay. The activities of aspartate transaminase (AST), lactate dehydrogenase (LDH) and creatine kinase (CPK) were measured by biochemical assay. The increase in blood glucose, glycated hemoglobin and systolic blood pressure in diabetic rats were reduced upon green tea treatment. The activities of AST, LDH and CPK were significantly increased in serum whereas decreased in cardiac tissues in diabetic rats representing the cardiac damage. Administration of green tea to diabetic rats significantly ameliorates these enzyme activities. There was no significant difference in the myocardial collagen content among the experimental rats. A significant (P<0.05) increase in collagen linked Maillard-type fluorescence and decrease in collagen solubility in the myocardium of diabetic rats as compared to control rats (0.955+/-0.02 versus 0.683+/-0.04 and 30+/-1.41 versus 45.17+/-1.17, respectively) indicates the increase in advanced glycation end products formation and degree of collagen cross-linking. Green tea administration to diabetic rats significantly (P<0.05) decreased the fluorescence (0.73+/-0.02) whereas increased the solubility of collagen (41.5+/-1.04) indicating the reduction in advanced glycation end products and collagen cross-linking. The present study reveals that green tea by ameliorating myocardial collagen characteristics may provide a therapeutic option in the treatment of cardiovascular complications of diabetes.

Topics: Animals; Aspartate Aminotransferases; Blood Glucose; Blood Pressure; Caffeine; Camellia sinensis; Cardiovascular Agents; Catechin; Collagen; Creatine Kinase; Diabetes Mellitus, Experimental; Fibrosis; Glycated Hemoglobin; Glycation End Products, Advanced; Glycosylation; Heart Diseases; Hypoglycemic Agents; L-Lactate Dehydrogenase; Maillard Reaction; Male; Myocardium; Plant Extracts; Plant Leaves; Protein Processing, Post-Translational; Rats; Rats, Wistar; Solubility; Spectrometry, Fluorescence

We describe a male patient with Fabry disease and use this case study to illustrate the importance of a detailed cardiovascular evaluation and the role of supportive therapy in routine management of the disease. The major areas of discussion include the management of exertional chest pain, progressive heart failure and the diagnosis and treatment of atrial and ventricular arrhythmia.. In the era of enzyme replacement therapy, conventional pharmacological and device-based therapies remain central to the management of cardiovascular symptoms and the prevention of complications, such as arrhythmia and stroke.

Topics: Cardiovascular Agents; Fabry Disease; Heart Diseases; Humans; Male; Middle Aged

Topics: Adult; Angina Pectoris; Anticoagulants; Biopsy; Cardiovascular Agents; Endocardium; Heart Diseases; Heart Failure; Humans; Magnetic Resonance Imaging; Male; Myocarditis; Parvoviridae Infections; Parvovirus B19, Human; Thrombosis

Topics: Calcium; Cardiovascular Agents; Cell Death; Heart; Heart Diseases; Humans; Hypocalcemia; Infant

The authors aimed to compare the clinical outcomes with repeat drug-eluting stent (DES) implantation utilizing the same type versus an alternate DES type for in-stent restenosis (ISR) of DES.. : DES are proven as an effective treatment for bare metal ISR.. A cohort of 116 patients previously treated with a sirolimus-eluting stent (SES) or a paclitaxel-eluting stent (PES) who presented with angiographic ISR were treated with repeat DES. Of these, 62 (53.4%) were treated with different DES and 54 (46.6%) were treated with the same DES. This cohort was followed for clinical events at 30 days, 6 months, and 1 year.. Baseline characteristics were similar except for more diabetes among patients receiving the different type of DES. Of the 116, overall 16.4% of the DES were implanted for previous ISR and 2.6% had previously received brachytherapy. At 6 months, the overall target vessel revascularization (TVR) rate was 12.2% for the entire cohort. The TVR-major adverse cardiac event (MACE) rate for the patients treated with different DES was 14.5% and 16.7% for the same DES (P = 0.750). Overall TVR rate at 1 year was 28.8%. The TVR-MACE was 32.6% for different DES and 35.0% for the same DES (P = 0.814).. Reimplantation of DES for the treatment of DES ISR (same or different) is safe but associated with a high rate of recurrences at 1 year regardless of the initial DES type. Other treatment modalities for ISR of DES should be considered to further improve the overall TVR-MACE.

Topics: Aged; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Angiography; Coronary Restenosis; Female; Follow-Up Studies; Heart Diseases; Humans; Kaplan-Meier Estimate; Male; Metals; Middle Aged; Paclitaxel; Prosthesis Design; Reoperation; Secondary Prevention; Sirolimus; Stents; Time Factors; Treatment Outcome

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

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

This study examines the construction of the "heart disease candidate" in advertisements for cardiovascular drugs in Scandinavian medical journals.. All advertisements for cardiovascular drugs (n = 603) in Scandinavian medical journals (Denmark, Finland, Norway, and Sweden) in 2005 were collected. Only advertisements that portray users (n = 289, 48% of the advertisements) were analyzed.. The results show that coronary candidacy is constructed as a male condition in half of the advertisements for cardiovascular drugs. The advertisements suggest a gendering of heart disease: men are the major victims of heart failure and cardiac insufficiency, and women are in need of cholesterol-lowering drugs. The cardiovascular drug advertisements portray a restoration of men's hyperactive agency, valorized by means of sporty images, by drawing on masculinity as a fixed trait and behavior. Hypercholesterolemia as a woman's disease reproduces the tyranny of slimness for women: Only women's stoutness is medicalized, and there are no pictures of heavy men.. The findings point to the public health implications of gendered images of coronary candidacy in medical advertising.

Topics: Advertising; Cardiovascular Agents; Denmark; Drug Industry; Female; Finland; Health Education; Heart Diseases; Humans; Male; Norway; Sex Factors; Social Identification; Sweden; Women's Health

Little information is available concerning adverse drug events (ADEs) in cardiac patients. Therefore, the investigators report the results of cardiac patients in an ADE surveillance program, with the intent of reducing the frequency of future events. All reported adverse drug reactions and medication errors in cardiac patients over a 5-year period at Brigham and Women's Hospital were reviewed. There were 547 ADEs in cardiac patients, a rate of 1.9 events for every 100 patient admissions. Preventable ADEs most often occurred during medication administration (34.2%), with wrong rate or frequency of medication administration the most widespread event. Cardiovascular agents (29.8%), anticoagulants (28.5%), and antimicrobial agents (10.8%) were the most common drug classes associated with ADEs. Injury or prolonged hospitalization occurred in 5.3% of patients. ADEs occurred most frequently on the admission day, on weekdays, and in the early morning hours. Peak frequencies of ADEs coincided with nursing shift changes. In conclusion, ADEs occur often in hospitalized cardiac patients and affect 2 of every 100 patient admissions. Given the high percentage of ADEs associated with drug administration, more resources should be directed at this step of medication use. Focusing interventions around nursing shift changes may further enhance preventive strategies.

Topics: Adverse Drug Reaction Reporting Systems; Anticoagulants; Boston; Cardiovascular Agents; Drug Utilization Review; Drug-Related Side Effects and Adverse Reactions; Heart Diseases; Hospitalization; Hospitals, University; Hospitals, Urban; Humans; Medication Errors; Nursing Staff, Hospital; Personnel Staffing and Scheduling; Time Factors

Topics: Cardiac Surgical Procedures; Cardiovascular Agents; Diagnostic Imaging; Heart Diseases; Humans; Lipid Metabolism

We examined how repolarization and depolarization abnormalities contribute to the development of extrasystoles and subsequent ventricular fibrillation (VF) in a model of the Brugada syndrome.. Repolarization and depolarization abnormalities have been considered to be mechanisms of the coved-type ST-segment elevation (Brugada-electrocardiogram [ECG]) and development of VF in the Brugada syndrome.. We used high-resolution (256 x 256) optical mapping techniques to study arterially perfused canine right ventricular wedges (n = 20) in baseline and in the Brugada-ECG produced by administration of terfenadine (5 micromol/l), pinacidil (2 micromol/l), and pilsicainide (5 micromol/l). We recorded spontaneous episodes of phase 2 re-entrant (P2R)-extrasystoles and subsequent self-terminating polymorphic ventricular tachycardia (PVT) or VF under the Brugada-ECG condition and analyzed the epicardial conduction velocity and action potential duration (APD) restitutions in each condition.. Forty-one episodes of spontaneous P2R-extrasystoles in the Brugada-ECG were successfully mapped in 9 of 10 preparations, and 33 of them were originated from the maximum gradient of repolarization (GR(max): 176 +/- 54 ms/mm) area in the epicardium, leading to PVT (n = 12) or VF (n = 5). The epicardial GR(max) was not different between PVT and VF. Wave-break during the first P2R-extrasystole produced multiple wavelets in all VF cases, whereas no wave-break or wave-break followed by wave collision and termination occurred in PVT cases. Moreover, conduction velocity restitution was shifted lower and APD restitution was more variable in VF cases than in PVT cases.. Steep repolarization gradient in the epicardium but not endocardium develops P2R-extrasystoles in the Brugada-ECG condition, which might degenerate into VF by further depolarization and repolarization abnormalities.

Topics: Action Potentials; Animals; Cardiovascular Agents; Disease Models, Animal; Dogs; Electrocardiography; Electrophysiologic Techniques, Cardiac; Endocardium; Heart Conduction System; Heart Diseases; Heart Ventricles; Lidocaine; Male; Pericardium; Pinacidil; Tachycardia, Ventricular; Terfenadine; Ventricular Fibrillation

Topics: Belgium; Cardiovascular Agents; Combined Modality Therapy; Europe, Eastern; Heart Diseases; History, 20th Century; Humans; Patient Compliance; Patient Education as Topic; Primary Health Care; Quality of Life; Rehabilitation Centers

The clinical profiles and outcomes of patients treated surgically for acute type B aortic dissection (ABAD) are often reported for those in small series or for those cared for at a single institution over a long time period, during which a continuous evolution in techniques has occurred. Accordingly, we sought to evaluate the clinical features and surgical results of patients enrolled in the International Registry of Acute Aortic Dissection by identifying primary factors that influenced surgical outcome and estimating average surgical mortality for ABAD in the current era.. A comprehensive analysis of 290 clinical variables and their relation to surgical outcomes for 82 patients who required surgery for ABAD (from a population of 1256 patients; mean+/-SD age, 60.6+/-15.0 years; 82.9% male) and who were enrolled in the International Registry of Acute Aortic Dissection was performed. The overall in-hospital mortality was 29.3%. Factors associated with increased surgical mortality based on univariate analysis were preoperative coma or altered consciousness, partial thrombosis of the false lumen, evidence of periaortic hematoma on diagnostic imaging, descending aortic diameter >6 cm, right ventricle dysfunction at surgery, and shorter time from the onset of symptoms to surgery. Factors associated with favorable outcomes included radiating pain, normotension at surgery (systolic blood pressure 100 to 149 mm Hg), and reduced hypothermic circulatory arrest time. The 2 independent predictors of surgical mortality were age >70 years (odds ratio, 4.32; 95% confidence interval, 1.30 to 14.34) and preoperative shock/hypotension (odds ratio, 6.05; 95% confidence interval, 1.12 to 32.49).. The present study provides insights into current-day clinical profiles and surgical outcomes of ABAD. Knowledge about different preoperative clinical conditions may help surgeons in making treatment decisions among these high-risk patients.

Topics: Acute Disease; Aged; Anastomosis, Surgical; Antihypertensive Agents; Aortic Aneurysm, Thoracic; Aortic Dissection; Aortic Rupture; Atherosclerosis; Blood Vessel Prosthesis Implantation; Cardiovascular Agents; Comorbidity; Disease Susceptibility; Europe; Female; Follow-Up Studies; Heart Diseases; Hemodynamics; Hospital Mortality; Humans; Hypertension; Japan; Male; Marfan Syndrome; Middle Aged; Paraplegia; Postoperative Complications; Registries; Spinal Cord Ischemia; Stents; Survival Analysis; Treatment Outcome; United States

Topics: Age Factors; Aged; Aged, 80 and over; Attitude of Health Personnel; Cardiovascular Agents; Heart Diseases; Humans; Practice Guidelines as Topic; Risk Assessment

In 18 horses, the pulmonary artery wedge pressure and the heart rate were measured during pharmacological stress load. 12 horses were healthy (4 trained, 8 untrained) and 6 horses had a heart disease (3 trained, 3 untrained). Pharmacological stress induction was carried out with the sympathomimetic drug dobutamine at a dosage rate of 7.5 microg/kg/min over 10 minutes of infusion. At the fourth minute, the parasympatholytic drug atropine was administered (5 microg/kg bw), and the heart rate and the pulmonary artery wedge pressure were continuously measured over 26 minutes. During sole dobutamine infusion, a significant decrease in heart rate and a significant increase in pulmonary artery wedge pressure were observed. After the application of atropine in the fourth minute, a significant increase in heart rate (from 35.7 +/- 6 up to 106 +/- 38/ min) and in pulmonary artery wedge pressure (from 15.7 +/- 3 up to 24 +/- 8.6 mmHg) were visible in the group of healthy horses. The horses with heart diseases had a significantly higher increase in both parameters (heart rate and pulmonary artery wedge pressure) with a significantly positive correlation (r = 0.7). The heart rate increased in the horses with heart diseases from 35.2 +/- 2,8 beats/min up to 132 +/- 45.7 beats/min and the pulmonary artery wedge pressure increased from 17.3 +/- 3,2 mmHg up to 32.7 +/- 13 mmHg. The cardiac status (healthy or heart disease) as well as the training level of the horses (untrained or trained) had a significant influence on the heart rate and the pulmonary artery wedge pressure. The untrained horses (healthy and heart disease) showed significantly higher values over a longer period of time than did the trained horses with the same cardiac status. Additionally the influence of pharmacological stress induction on echocardiographic parameters was investigated. The left atrial size (p = 0.015) and left ventricular diameter were significanly different in the systole (p = 0.008) and in the diastole (p = 0.001) between healthy horses and horses with heart diseases. All horses showed a positive correlation between the pulmonary artery wedge pressure and the left atrial size (r = 0.8), as well as between the left ventricular systolic (r = 0.6) and the diastolic diameter (r = 0.6). The correlation between the pulmonary artery wedge pressure and the left atrial size was nearly the same in the healthy horses (r = 0.74) and in the horses with heart diseases (r = 0.76). Regarding the traini

Topics: Animals; Atropine; Cardiovascular Agents; Case-Control Studies; Dobutamine; Echocardiography; Female; Heart Diseases; Heart Rate; Horse Diseases; Horses; Male; Parasympatholytics; Pulmonary Wedge Pressure; Stress, Physiological; Sympathomimetics; Time Factors

Azidothymidine, a nucleoside-analogue reverse transcriptase inhibitor (NRTI), is a commonly used antiretroviral drug in AIDS treatment, however its use is limited by severe toxic side effects due to its influence on mitochondria that result in myopathy, particularly affecting the cardiac muscle. We suggest that effective protection of azidothymidine-induced cardiopathology can be expected from drugs that are capable of targeting mitochondria. Therefore the present study in mice was carried out with mildronate, a cardioprotective drug of the aza-butyrobetaine class, which previously has been shown to act as a highly potent protector of mitochondrial processes. In our study, saline (control), azidothymidine (50 mg/kg), mildronate (50, 100 and 200 mg/kg), and azidothymidine + mildronate (at the doses mentioned) were injected intraperitoneally daily in separate groups of mice for two weeks. At the termination of the experiment, mice were sacrificed, the hearts were removed and cardiac tissue was examined morphologically and immunohistochemically. It was found that azidothymidine, compared to control and mildronate groups, induced major morphologic changes in cardiac tissue, which were manifestated as degeneration and inflammation. These changes were prevented when mildronate was co-administered with azidothymidine. Mildronate also reduced the azidothymidine-induced expression of nuclear factor kappaBp65 (NF-kappaBp65). The obtained data demonstrate a high ability of mildronate of preventing azidothymidine-induced cardiopathologic changes, and suggest mildronate's indirect action on azidothymidine-caused oxidative stress reactions leading to mitochondrial dysfunction. This offers a rational combination of mildronate with azidothymidine or other anti-HIV drugs for beneficial application in AIDS therapy.

Topics: Animals; Cardiovascular Agents; Disease Models, Animal; Heart Diseases; Methylhydrazines; Mice; Mice, Inbred ICR; Mitochondria; Zidovudine

To develop HPLC-UV/ELSD and HPLC-UV/MS3 fingerprints of Japan Jiuxin pill using multi-dimensional hyphenated methods and study on its chemical base.. Separation was performed on Altima C18 analytical column (250 mm x 4.6 mm ID, 5 microm). The mobile phases consisted of water containing 0.2% formic acid and acetonitrile was used as gradient elute. The flow rate was 1.0 mL x min(-1). An electrospray ion trap mass spectrometer was utilized for qualitative analysis and both positive and negative secondary ion scan mode were applied.. HPLC-UV/ELSD and HPLC-UV/ MS3 fingerprints of Japan Jiuxin pill with well separation and reproducibility were obtained. Totally 21 components in the complex formula were identified and the chemical structural information of glycocholic acid and its isomer were suggested.. The research is propitious to offer an effective and reliable pattern for analyzing Japanese Kampo Medicines as well as its quality control.

Topics: Cardiovascular Agents; Chromatography, High Pressure Liquid; Heart Diseases; Humans; Japan; Medicine, Chinese Traditional; Spectrometry, Mass, Electrospray Ionization

Topics: Animals; Anti-Arrhythmia Agents; Cardiovascular Agents; Crataegus; Heart Diseases; Humans; Phytotherapy; Plant Extracts; Vascular Diseases

Topics: Bias; Cardiovascular Agents; Crime; Databases, Nucleic Acid; Drug Combinations; Forensic Sciences; Gene Frequency; Genetic Variation; Genetics, Medical; Heart Diseases; Humans; Hydralazine; Hypertension; Isosorbide Dinitrate; Pharmacogenetics; Phenotype; Polymorphism, Single Nucleotide; Racial Groups

Topics: Cardiovascular Agents; Heart Diseases; Humans; Intraoperative Complications; Myocardial Infarction; Risk Factors; Surgical Procedures, Operative

Topics: Bronchodilator Agents; Cardiovascular Agents; Drug Interactions; Drug Therapy, Combination; Heart Diseases; Humans; Pulmonary Disease, Chronic Obstructive

Patients with kidney disease and acute myocardial infarction (AMI) receive standard therapy, including thrombolytic medication, less frequently than patients with normal kidney function. Our goal is to identify potential differences in thrombolytic medication delays and thrombolytic-associated bleeding events by severity of kidney disease.. This is a retrospective cohort analysis of Cooperative Cardiovascular Project data for all Medicare patients with AMI from 4,601 hospitals. Outcome measures included time to administration of thrombolytic medication censored at 6 hours and bleeding events.. Of 109,169 patients (mean age, 77.4 years; 50.6% women), 13.9% received thrombolysis therapy. Average time to thrombolytic therapy was longer in patients with worse kidney function. Adjusted hazard ratios for minutes to thrombolytic therapy were 0.83 (95% confidence interval [CI], 0.79 to 0.87) for patients with a serum creatinine level of 1.6 to 2.0 mg/dL (141 to 177 micromol/L) and 0.58 (95% CI, 0.53 to 0.63) for patients with a creatinine level greater than 2.0 mg/dL (>177 micromol/L) or on dialysis therapy compared with those with normal kidney function. Odds ratios for bleeding events in patients administered thrombolytics versus those who were not decreased with worse kidney function: adjusted odds ratios, 2.28 (95% CI, 2.16 to 2.42) in patients with normal kidney function and 1.84 (95% CI, 1.09 to 3.10) in dialysis patients.. Patients with worse kidney function experienced treatment delays, but were not at greater risk for thrombolysis-associated excess bleeding events. Physician concerns of thrombolytic-associated bleeding may not be sufficient reason to delay the administration of thrombolytic medication.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Cohort Studies; Comorbidity; Creatinine; Databases, Factual; Diabetes Mellitus; Female; Fibrinolytic Agents; Heart Diseases; Hemorrhage; Humans; Hypertension; Kidney Diseases; Life Tables; Male; Medicare; Myocardial Infarction; Peptic Ulcer; Proportional Hazards Models; Retrospective Studies; Sampling Studies; Thrombolytic Therapy; Time Factors; United States

The prevalence of prescription medication use among older people increases with advancing age and is related to their comorbidities. Cardiovascular medication is the medication category that is the most commonly prescribed. We retrospectively determined the repercussion of the cardiological consultation of the Hôpital de gériatrie de Genève on the cardiovascular medication. For the year 2001, 191 hospitalized patients were randomely selected and their treatment before and after the consultation was compared. The treatment was simplified after consultation considering the number of medication classes, drugs, and pills. Adverse effect (11% of consultations) is the main reason for interrupting a medication. The number of medication before consultation is an important factor to decide whether the treatment needs to be simplified. The medication cost is not modified. By simplifying treatment the cardiological consultation reduces the adverse effects of medication and probably improves therapeutic adherence. A prospective study is necessary to confirm these data and estimate their long term consequences.

Topics: Aged; Cardiology; Cardiovascular Agents; Comorbidity; Drug Interactions; Heart Diseases; Humans; Patient Compliance; Referral and Consultation; Retrospective Studies

In this study, patients with heart diseases were classified into 2 groups: Warfarin user and Warfarin non-user, and six salivary components were determined to assess intraoral pathologic conditions. Groups of healthy subjects and patients with periodontal disease without receiving any medication were set as control groups, and they were compared with those of the 2 groups with heart diseases. In patients with heart diseases in both the groups, albumin (ALB) level was found to be significantly higher compared to that in the control groups, and it was significantly higher in the patient group receiving Warfarin user and Warfarin non-user compared to that in the patient group with periodontal disease. C-reactive protein (CRP) levels were found to be higher in both the groups with heart diseases than those in the healthy group. Correlations between various salivary components and the clinical parameters were examined, showing significant correlations between ALB and gingival index (GI) and clinical attachment level (CAL), and between alanine aminotransferase (ALT) and GI, probing depth (PlI), bleeding on probing (BOP) and CAL. Significant correlations were also found between creatine kinase (CK) and PlI, GI and BOP. Thus, it was suggested that ALB and CRP might serve as the markers of intraoral pathologic conditions, and CK and ALT might serve as those alternative to GI.

Topics: Adult; Aged; Alanine Transaminase; Albumins; Anticoagulants; Aspartate Aminotransferases; Biomarkers; C-Reactive Protein; Cardiovascular Agents; Creatine Kinase; Dental Plaque Index; Gingival Hemorrhage; Heart Diseases; Humans; Middle Aged; Periodontal Attachment Loss; Periodontal Diseases; Periodontal Index; Periodontal Pocket; Saliva; Salivary Proteins and Peptides; Warfarin

Topics: Cardiovascular Agents; Comorbidity; Female; Health Knowledge, Attitudes, Practice; Health Priorities; Heart Diseases; Humans; Life Style; Practice Guidelines as Topic; Risk Assessment; Risk Factors; Stroke

Topics: Cardiac Surgical Procedures; Cardiology; Cardiovascular Agents; Echocardiography; Electrocardiography; Heart Diseases; History, 18th Century; History, 19th Century; History, 20th Century; Humans; Periodicals as Topic; Sweden

Topics: Cardiovascular Agents; Heart Diseases; Humans; Interprofessional Relations; Patient Compliance; Pharmacists; Pharmacy Service, Hospital; Professional Role; Quality of Life

Topics: Adult; Aged; Cardiovascular Agents; Drug Costs; Heart Diseases; Humans; Managed Care Programs; Middle Aged; Patient Compliance; United States

To better define the reported increased digitalis-like immunoreactive substances (DLIS) in neonatal plasma, we studied the relation among plasma DLIS level, blank intensity (BLK-I) value at FPIA measurement and plasma total bilirubin level.. The DLIS levels were measured in 10 neonates with or without jaundice and 10 infants in good health, using fluorescence polarization immunoassay (FPIA) and microparticle enzyme immunoassay (MEIA). BLK-I value and plasma total bilirubin level were also measured simultaneously.. In neonates with jaundice, DLIS using FPIA, BLK-I and total bilirubin level were 0.58 +/-0.13 ng/mL, 2598 +/- 408, and 17.98 +/- 1.13 mg/dL, respectively, before phototherapy, and 0.33 +/-0.06 ng/mL, 1886 +/- 237, and 15.16 +/- 2.07 mg/dL after phototherapy. Corresponding values in neonates without jaundice were (DLIS: 0.34 +/-0.04 ng/mL; BLK-I: 1,764 +/- 278; total bilirubin: 10.37 +/- 4.54 mg/dL); in healthy infants (0.12 +/-0.06 ng/mL, 400.7 +/- 4.6 and 0.42 +/- 0.13 mg/dL, respectively) and in healthy volunteers (0.10 +/-0.07 ng/mL, 403.1 +/- 8.4, and 0.58 +/- 0.30 mg/dL, respectively). Using MEIA, DLIS was not detected in 10 neonates, 10 infants and 20 healthy volunteers.. A fluorescent compound related to bilirubin increased the BLK-I value in the measurement of neonatal plasma using FPIA. The fluorescence was not the result of endogenous digitalis-like factors.

Topics: Bilirubin; Cardenolides; Cardiovascular Agents; Child, Preschool; Digoxin; Female; Fluorescence Polarization Immunoassay; Heart Diseases; Humans; Infant; Infant, Newborn; Jaundice; Male; Phototherapy; Reference Values; Saponins

Topics: Aldosterone; Cardiovascular Agents; Cardiovascular Physiological Phenomena; Heart Diseases; Humans; Hyperaldosteronism; Hypertension; Mineralocorticoid Receptor Antagonists

Topics: Adolescent; Adult; Age Factors; Aged; Animals; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Lewis Lung; Cardiotonic Agents; Cardiovascular Agents; Chelating Agents; Child; Clinical Trials as Topic; Doxorubicin; Echocardiography; Electrocardiography; Female; Heart; Heart Diseases; Humans; Immunosuppressive Agents; Leukemia, Experimental; Male; Mice; Mice, Inbred C57BL; Neoplasms; Neoplasms, Experimental; Razoxane; Time Factors

Topics: Age Factors; Cardiovascular Agents; Female; Heart Diseases; Hormone Replacement Therapy; Humans; Middle Aged

To evaluate the maternal and fetal outcome of pregnancies complicated by cardiac disease in a developing country.. A retrospective analysis was carried out of 207 pregnancies in women with cardiac disease who delivered at >or=28 weeks of gestation from June 1994 through December 2000 at a tertiary care center.. Rheumatic heart disease (n=183, 88%) with isolated mitral stenosis (n=71) was the predominant cardiac problem. Septal defects were the most common form of congenital heart disease (n=24). In 28 (13.52%) women, the diagnosis of cardiac disease was made during pregnancy. Cardiac complications were noted in 62 (29.95%) and fetal complications in 42 (20.28%) pregnancies. Patients in NYHA class I/II (n=175, 84.54%) had fewer maternal complications and their babies had a higher birth weight than those in NYHA class III/IV (n=32, 15.45%). Cardiac intervention was performed prior to pregnancy in 111 (60.65%) patients with rheumatic heart disease: PTMC/CMV in 73 and valve replacement (VR) in 38. Maternal and fetal outcome was better in patients with prosthetic valves (n=38) and the majority (97.4%) of them remained in NYHA class I/II. Cardiac intervention was safely carried out during pregnancy in 10 women (PTMC in 7, CMV in l, and VR in 2). One of them developed congestive cardiac failure during labor. None of the newborns of the 41 women who had received anticoagulants had any congenital malformation.. Rheumatic heart disease was the predominant type. Patients in NYHA class I/II had a better maternal and fetal outcome than those in NYHA class III/IV. Surgical correction of the cardiac lesion prior to pregnancy was associated with better pregnancy outcome. Pregnant women with prosthetic valves tolerated pregnancy well.

Topics: Adolescent; Adult; Cardiovascular Agents; Female; Heart Defects, Congenital; Heart Diseases; Heart Valve Prosthesis; Humans; India; Infant, Low Birth Weight; Infant, Newborn; Labor, Obstetric; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Pregnancy, High-Risk; Retrospective Studies; Rheumatic Heart Disease; Risk Assessment; Severity of Illness Index

For Medicare beneficiaries who report having heart disease, drug coverage and type of supplemental health insurance affect the likelihood of usage and costs of heart medications, but not the extent of usage. Nearly one in five does not use heart medications and of the latter, one-third lack drug coverage. Some non-users without drug coverage go without prescribed heart medications because of limited financial access. Compared to non-users with coverage, they utilize medical provider services more, and if hospitalized, their inpatient costs are twice as high. Medicare may accrue cost savings by providing drug coverage to and monitoring these at-risk beneficiaries.

Topics: Aged; Aged, 80 and over; Cardiovascular Agents; Female; Health Expenditures; Health Services Accessibility; Heart Diseases; Humans; Insurance Coverage; Insurance, Pharmaceutical Services; Male; Medicare; Medicare Part B; Multivariate Analysis; United States

Topics: Aged; Aging; Cardiovascular Agents; Drug Combinations; Heart Diseases; Humans; Life Style

There is increasing interest in studying trends in drug utilization because drug costs are the fastest growing sector of the health care system.. To focus on the trends in the utilization of and expenditures for cardiovascular drugs in Canada by drug class and by province over a six-year period.. Data from the IMS Health Canada CompuScript Audit database were used for this study from the period of February 1996 to January 2002. Patterns of drug utilization and expenditures in Canada were described for cardiovascular drug classes, individual agents within classes and by provincial analyses.. Substantial increases in both the utilization of and the expenditures for cardiovascular medications have occurred in Canada over the last six years. Newer medication classes such as angiotensin converting enzyme inhibitors and statins now comprise the majority of cardiovascular drugs prescribed, along with continued high use of diuretics. Increases in some drug classes, such as angiotensin converting enzyme inhibitors, statins and beta-blockers, appear to be based on trial evidence or guidelines. However, marketing may play a larger role in the increases in use of angiotensin receptor blockers and specific drugs, such as amlodipine besylate and atorvastatin, because their increased utilization cannot be explained by major clinical trial evidence and/or practice guidelines.. Changes in patterns of cardiovascular drug utilization and expenditures in Canada may be associated with clinical trial evidence, clinical practice guidelines, policy changes and/or marketing initiatives.

Topics: Canada; Cardiovascular Agents; Drug Costs; Drug Prescriptions; Drug Utilization; Health Expenditures; Heart Diseases; Humans; Practice Patterns, Physicians'

Topics: Cardiovascular Agents; Cation Transport Proteins; Clinical Trials as Topic; DNA-Binding Proteins; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels; Heart Diseases; Humans; Long QT Syndrome; Potassium; Potassium Channels; Potassium Channels, Voltage-Gated; Trans-Activators; Transcriptional Regulator ERG

Circulatory disturbances may occur during and after the treatment of acute lymphoblastic leukemia (ALL). The reasons are: leukemic infiltrations of the heart, anaemia, renal disturbances, infections, cardiotoxic drugs, especially anthracyclines (Atc). The aim of the study was echocardiographic assessment of circulatory system in patients during and 3-5 years after ALL therapy in childhood. The study group (group B) consisted of 20 children, aged 1-16 years, who underwent Atc treatment with cumulative doses 155.8-330 mg/m2 and cardioprotective agent--dexrazoxane. In this group echocardiography was performed before the treatment as well as after 1, 6, 12 months and 3 years. The retrospective group (R) consisted of 36 persons aged 12-24 years, examined 3-5 years after the completion of ALL treatment, who had undergone the treatment with Atc in doses 148.6-416.7 mg/m2 without cardioprotection. The control group (K) consisted of 28 healthy volunteers, aged 9-25 years. In all subjects echocardiography was performed, standard measurements taken, systolic and diastolic indices of left ventricle (LV) function calculated. In patients during and 3-5 years after the treatment neither LV dilatation nor abnormal wall-thickness was found. The systolic indices remained normal. In the group B echocardiographic indices did not change significantly during 3 years of treatment and did not correlate with growing cumulative Atc doses. In this group isovolumetric relaxation time (IVRT) was significantly longer, what emphasized the need of further clinical and echocardiographic follow-up.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Cardiovascular Agents; Case-Control Studies; Child; Child, Preschool; Cyclophosphamide; Doxorubicin; Drug Therapy, Combination; Echocardiography; Female; Heart Diseases; Humans; Infant; Male; Paclitaxel; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Razoxane; Taxoids; Time Factors; Ventricular Function, Left; Ventricular Function, Right

Topics: Antidepressive Agents; Arrhythmias, Cardiac; Autonomic Nervous System; Cardiovascular Agents; Depressive Disorder; Drug Interactions; Heart Diseases; Humans

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Cardiovascular Agents; Coronary Artery Bypass; Heart Diseases; Humans

Topics: Antibiotics, Antineoplastic; Cardiovascular Agents; Heart Conduction System; Heart Diseases; Humans; Razoxane

Normal physiological changes in the cardiovascular system in pregnancy such as increase in cardiac output, vasodilatation and hypervolemia are of clinical relevance as they are able to aggravate, mask or even imitate cardiovascular diseases. There is an increase of cardiac size and volume during pregnancy; furthermore hormonal changes lead to diaphragmatic elevation and barrel-shaped thorax followed by a rotation of the cardiac axis to the left (15 degrees-30 degrees). Cardiac topography and size, changes in cardiac functioning and physiology as well as hemodynamic changes lead to auscultatory and ECG changes (i.e. S1-Q3-type, ST-depression, T wave flattening). In addition there is a high incidence of functional systolic and diastolic sounds during pregnancy, which are also able to imitate cardiovascular diseases. The physiological changes in pregnancy are similar to those under heavy exercise. This results in continuous cardiac stress during the whole pregnancy. This stress is specifically high from the 28th to the 34th week of pregnancy and in the post-partum period; the maximum of cardiac stress is reached during labor. Important for the specific cardiac risk during pregnancy is not the type of heart disease but cardiac functioning and the severity of complaints before pregnancy. Principally it has to be expected that preexisting heart diseases will experience an aggravation of one grade according to NYHA during pregnancy. In cases of heart diseases with shunt defects, with shunt defect and injured myocardium, with continuous arrhythmia or atrial fibrillation, patients are at extremely high risk of cardiac death. A termination of pregnancy should be considered in all patients with heart diseases grade III or IV according to NYHA, severe pulmonary hypertension, Eisenmenger's syndrome, severe aortic or pulmonary stenosis, Marfan's syndrome, and severe continuous cardiac insufficiency. The drug therapy of cardiac diseases during pregnancy depends on the specific type of heart disease. Prescription of most drugs is principally possible during pregnancy and breast feeding. However, for most drugs there is only very limited therapeutic experience during this period. Definitively contraindicated during pregnancy and breast feeding are ACE inhibitors, angiotensin I and II blocking agents, vasopeptidase inhibitors and molsidomin, a NO-prodrug. In life-threatening conditions, however, sometimes it will be necessary to administer drugs with only poor experiences

Topics: Cardiovascular Agents; Female; Gestational Age; Heart Diseases; Hemodynamics; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications, Cardiovascular; Puerperal Disorders; Risk Factors

The prospective study compares prescribed drugs of 192 primarily cardiological patients at discharge and 7 weeks later in ambulatory care. The data were determined by discharge summaries and by standardized patient-questionnaires. The drug division was made with the ATC-classification according to the recommendations of the World Health Organisation for Drug Utilisation Studies. The intraindividual cost comparison was calculated by current pharmacy sale prices. The findings were changes in hospital discharge medications in ambulatory care in over 2/3 of the cases. The most frequent change was the additional prescribing of drug groups. The average daily tablet number increased in patients with the same or worsened subjective feeling after discharge. Additionally we found in a number of patients a change of drug therapy within the ATC-groups, or in fact, withdrawal of drug therapy all together. The frequency of changes increased with the number of patient/doctor contacts. The observation that the average daily therapeutical cost decreased just slightly could give an indication that cost saving was a minor part of the doctors decision for drug changing. However, the frequency of changes has shown to be dependent upon the specialities of the physician or pharmaceutical group.

Topics: Adult; Aged; Aged, 80 and over; Ambulatory Care; Cardiovascular Agents; Cost Control; Drug Costs; Drug Prescriptions; Female; Germany; Heart Diseases; Humans; Male; Middle Aged; Patient Discharge

In black Africa, and particularly in Togo, management of thyreotoxicosis is not simple. The intervention of several specialists and effective patient collaboration is needed. In a majority of cases, the patient's apprehensions, financial problems, and taboos prevent correct management. We report 30 cases of thyreotoxicosis in 82 patients with thyroid disease seen over a 5-year period in the Internal Medicine and Cardiology Department of the Lomé teaching hospitals. Graves' disease was the most frequent (83.33%), followed by multinodular goiter (10%) and toxic nodule (6.67%). Diagnosis was strictly clinical in 53.33% of the cases. The main complication was cardiothyreosis in 46.67% of the patients. Drug treatment was used. Short-term results (4 - 6 weeks) was favorable in 96.67% of the cases. A percentage (65.41%) were lost to follow-up after discharge. The main impairment encountered for the management of thyreotoxicosis was financial and economical difficulties not specific to the disease. Other problems included the lack of diagnostic and therapeutic means and insufficient cooperation between the surgeon, the cardiologist and the endocrinologist.

Topics: Adult; Carbimazole; Cardiovascular Agents; Developing Countries; Drug Therapy, Combination; Exophthalmos; Female; Follow-Up Studies; Goiter, Nodular; Graves Disease; Health Services Needs and Demand; Heart Diseases; Hospitalization; Hospitals, University; Humans; Hypnotics and Sedatives; Interprofessional Relations; Iodine; Male; Patient Care Team; Sweating; Thyroidectomy; Thyrotoxicosis; Togo; Tremor

Topics: Adult; Arrhythmias, Cardiac; Cardiomyopathies; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Heart Diseases; Humans; Myocardial Infarction; Prognosis; Resuscitation; Risk Factors

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Heart Diseases; Humans; Instillation, Drug; Pericardium

The authors prospectively investigated the incidence of asystole (absence of heartbeat for 5 seconds) in elderly patients receiving electroconvulsive therapy (ECT) at a university-based geriatric psychiatry unit. In all, 65.8% of patients experienced asystole at some time during their course of ECT. Those who experienced asystole were significantly younger (average age, 72.2) than those without asystole (average age, 77.0; P = 0.026) and were also less likely to have cardiac rhythm disturbances on electrocardiogram (P = 0.024). Medical history, history of cardiac disease, electrode placement, energy level, and number of ECT treatments did not predict asystole. Asystole is a common side effect of ECT in elderly patients. It was not associated with any untoward outcome. The fact that "old-old" patients and those with cardiac disease are less likely to experience asystole than younger, healthier patients is reassuring to practitioners of ECT.

Topics: Age Factors; Aged; Anesthetics; Cardiovascular Agents; Chi-Square Distribution; Electroconvulsive Therapy; Female; Geriatric Psychiatry; Heart Arrest; Heart Diseases; Humans; Male; Mood Disorders; Prospective Studies; Treatment Outcome

Topics: Anthracyclines; Antineoplastic Agents; Cardiovascular Agents; Heart; Heart Diseases; Humans

Topics: Cardiology; Cardiovascular Agents; Decision Making; Heart Diseases; Hemodynamics; Humans; Periodicals as Topic; Publishing

A cardiotoxic effect induced by adriamycin (by repeated i.v. administration to experimental rats in 7-day intervals of administration) begins to be manifested in the ECG record by prolongation of the S alpha T segment between days 14 and 20, on day 30 it is statistically significant. By means of this index, the known protective effect of dexrazoxane (the preparation Cardioxan) against adriamycin cardiotoxicity has been successfully confirmed in a four-week experiment. A comparative study (using the identical frequency of the dosing scheme and S alpha T segment as the decisive parameter) has revealed that antimet-as another original substance of the diketopiperazines group-also involves (though less significantly) protective effects against the toxic action of adriamycin.

Topics: Administration, Oral; Animals; Cardiovascular Agents; Doxorubicin; Drug Evaluation, Preclinical; Electroencephalography; Female; Heart Diseases; Myometrium; Piperazines; Rats; Rats, Wistar; Razoxane

The estimation of an individual patient's "resistance" to major surgery has become an complex matter. Clinical parameters allow risk stratification in a large number of patients who are about to undergo noncardiac surgery. Low risk patients can be "cleared" for surgery. Moderate risk patients should undergo further testing. Exercise testing and pharmacological stress testing with myocardial perfusion imaging can refine risk estimation in these patients. This risk stratification is well backed by scientific data, although most of it is derived from studies in the same very high risk population, i.e. patients scheduled for vascular surgery. Less hard evidence exists when it comes to the management of the high-risk patient. Coronary bypass surgery should probably be reserved for those in whom additional indications for this procedure exist. The perioperative use of beta-blockers can possibly reduce operative risk. Data on perioperative monitoring and anesthetic technique are not yet convincing. The relative merits of various perioperative management strategies will remain uncertain until randomised trials are performed to evaluate the alternatives systematically.

Topics: Age Factors; Anesthesia; Cardiovascular Agents; Coronary Angiography; Female; Heart Diseases; Heart Function Tests; Humans; Male; Myocardial Revascularization; Postoperative Complications; Preoperative Care; Risk Factors; Surgical Procedures, Operative

Topics: Cardiovascular Agents; Drug Utilization; Heart Diseases; Humans; Practice Patterns, Physicians'; United States

Topics: Adult; Antibiotics, Antineoplastic; Antineoplastic Agents; Cardiovascular Agents; Child; Heart; Heart Diseases; Humans; Neoplasms; Razoxane

Topics: Adult; Animals; Antibiotics, Antineoplastic; Cardiovascular Agents; Child; Heart; Heart Diseases; Humans; Neoplasms; Razoxane

Topics: Aged; Anxiety; Cardiovascular Agents; Depression; Female; Heart Diseases; Humans; Male; Middle Aged; Sleep Wake Disorders; Surveys and Questionnaires

Responses (473) were collated from a questionnaire sent to 5054 veterinarians in Australia enquiring about drug preferences for treating cardiac disease in dogs and cats. When treating a small breed dog with endocardiosis and mild left congestive heart failure, 74% of 472 respondents used a diuretic, 67% a theophylline derivative, 27% a vasodilator and 20% a positive inotrope. Frusemide was the preferred diuretic and digoxin the preferred inotrope, but vasodilator use varied. Low sodium diets were "often recommended" by 71% of respondents. Propranolol was preferred to diltiazem for treating feline hypertrophic cardiomyopathy. Digoxin was clearly preferred for treating supraventricular dysrhythmias, while lignocaine and digoxin were preferred equally for ventricular dysrhythmias. Respondents appeared more willing than US veterinarians to use theophylline derivatives and prasozin, and less inclined to employ nitrates, hydralazine, inotropes other than digoxin, and low sodium diets.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Australia; Cardiotonic Agents; Cardiovascular Agents; Cat Diseases; Cats; Digoxin; Diuretics; Dog Diseases; Dogs; Furosemide; Heart Diseases; Heart Failure; Lidocaine; Propranolol; Surveys and Questionnaires; Vasodilator Agents

Topics: Cardiovascular Agents; Critical Care; Emergencies; Heart Diseases; Humans

Topics: Cardiovascular Agents; Cardiovascular System; Heart Diseases; Humans

I have tried to highlight some of the extraordinary advances in cardiology over the last 25 years. Many conditions, however, such as primary pulmonary hypertension or cardiogenic shock remain as refractory to treatment now as then. There is no room for complacency. In addition the increasing cost of technology and the increasing demand for interventional cardiology are not being met. We are far behind our European colleagues in being able to provide this service.

Topics: Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Cardiology; Cardiovascular Agents; Diagnostic Imaging; Heart Diseases; History, 20th Century; Humans; Thrombolytic Therapy

Topics: Animals; Antibiotics, Antineoplastic; Cardiovascular Agents; Doxorubicin; Electric Stimulation; Guinea Pigs; Heart; Heart Diseases; In Vitro Techniques; Pyridazines

Topics: Cardiovascular Agents; Family; Heart Diseases; Humans; Infant, Newborn; Nursing Assessment

Cardiac patients are often on drugs. They invariably benefit from a rehabilitation programme where they may be seen more frequently than in a routine follow-up clinic. Rehabilitation units must keep alert for drug-induced adverse effects or symptomatic deterioration, as well as the more usual psychological and physical benefits they induce.

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Calcium Channel Blockers; Cardiovascular Agents; Digoxin; Diuretics; Heart Diseases; Humans; Nitrates; Warfarin

Topics: Adult; Aged; Cardiovascular Agents; Clonidine; Female; Heart Diseases; Hemodynamics; Humans; Male; Middle Aged; Postoperative Period; Time Factors

Topics: Adult; Cardiovascular Agents; Exercise Test; False Positive Reactions; Female; Health Services Misuse; Heart Diseases; Heart Rate; Humans; Male; Middle Aged

Topics: Blood Specimen Collection; Cardiovascular Agents; Dose-Response Relationship, Drug; Heart Diseases; Humans; Metabolic Clearance Rate; Monitoring, Physiologic; Protein Binding

The rational therapy of cardiovascular disease in horses requires a thorough knowledge of the pharmacology and pharmacokinetics of several specific drugs (digitalis, digoxin). Calcium solutions, dopamine, and dobutamine are frequently used to treat congestive heart failure in horses. Quinidine, procainamide, lidocaine, and propranolol are used to treat a variety of supraventricular and ventricular arrhythmias. Furosemide, a highly potent loop diuretic, is used to eliminate edema and promote diuresis. A thorough understanding of the applied pharmacology, dosage recommendations, toxicity, and practical considerations must be attained before these drugs can be used effectively.

Topics: Administration, Oral; Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Digoxin; Diuretics; Dobutamine; Dopamine; Drug Administration Schedule; Edema; Heart Diseases; Heart Failure; Heart Rate; Hemodynamics; Horse Diseases; Horses; Injections, Intravenous; Lidocaine; Procainamide; Propranolol; Quinidine

Topics: Age Factors; Aged; Anesthesia; Cardiovascular Agents; Coronary Disease; Heart Diseases; Hemodynamics; Humans; Middle Aged; Postoperative Complications; Preoperative Care; Risk; Surgical Procedures, Operative

Currently recommended dosages for the more commonly prescribed drugs discussed above are given in Table 3. The approach to the failing heart in the pediatric patient requires an understanding of the pathophysiology of heart failure and an understanding of the mechanisms, effects and clinical pharmacology of several classes of therapeutic agents. The pediatric patient differs in many respects from his adult counterpart in the manifestations of heart failure and in his response to drug therapy to treat heart failure.

Topics: Cardiotonic Agents; Cardiovascular Agents; Child; Digitalis Glycosides; Diuretics; Heart Diseases; Heart Failure; Hemodynamics; Humans; Infant; Pyridones; Sympathomimetics; Vasodilator Agents

Topics: Cardiovascular Agents; Female; Heart Diseases; Hemodynamics; Humans; Pregnancy; Pregnancy Complications, Cardiovascular

Topics: Cardiovascular Agents; Heart Diseases; Humans

Topics: Cardiovascular Agents; Heart Diseases; Humans; Nitrates

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Coronary Disease; Heart Diseases; Heart Failure; Heart Valve Diseases; Humans

Functional disorders of the left ventricle at rest and under 6 minutes lasting bicycle ergometer exercise of 50 W were studied in 249 patients after myocardial infarction. By means of well defined circumstances, measurement of pulmonary artery diastolic pressure with floating catheter allows evaluation of left ventricular enddiastolic pressure. The upper borderline of this pressure is 20 mmHg which was reached in 45% of patients in the age group under 40, in 75% in those who are 60 and older. Independent to other exercise limiting factors, like angina, ischemic ECG-changes, augmented heart volume, congestive heart failure or critical extrasystoles, it could be shown that measurement of pulmonary artery pressure in these cases is the base for rational therapy like administration of digitalis, vasodilator drugs or beta-adrenergic blocking agents. Furthermore it can be predicted wether physical training could be usefull or dangerous.

Topics: Adult; Age Factors; Aged; Cardiac Volume; Cardiovascular Agents; Electrocardiography; Exercise Test; Heart Diseases; Humans; Middle Aged; Myocardial Infarction; Pulmonary Wedge Pressure; Rest

Topics: Cardiovascular Agents; Drug Labeling; Heart Diseases; Humans; Patient Education as Topic; Physician-Patient Relations; Set, Psychology

Topics: Angina Pectoris, Variant; Calcium; Cardiovascular Agents; Diltiazem; Heart Diseases; Hemodynamics; Humans; Models, Biological; Muscle, Smooth, Vascular; Nifedipine; Vasoconstriction; Verapamil

Topics: Cardiovascular Agents; Heart Diseases; Humans

Topics: Animals; Cardiovascular Agents; Dog Diseases; Dogs; Emergencies; Heart Arrest; Heart Diseases; Heart Failure; Resuscitation; Shock

Topics: Calcium; Cardiovascular Agents; Heart Diseases; Humans; Resuscitation

Topics: Anaphylaxis; Cardiovascular Agents; Drug Hypersensitivity; Electrocardiography; Heart Diseases; Humans; Serum Sickness

Topics: Cardiovascular Agents; Cardiovascular Diseases; Electrocardiography; Electrodes; Exercise Test; Heart; Heart Diseases; Humans; Reference Values

Topics: Anti-Arrhythmia Agents; Cardiac Glycosides; Cardiovascular Agents; Heart Diseases; Humans

Topics: Aging; Cardiovascular Agents; Digitalis; Digitalis Glycosides; Diuretics; Drug Tolerance; Geriatrics; Heart Diseases; Iatrogenic Disease; Norway; Statistics as Topic; Toxicology

Topics: Adolescent; Amyl Nitrite; Atropine; Blood Protein Electrophoresis; Cardiovascular Agents; Dihydroergotoxine; Electrocardiography; Ergot Alkaloids; Heart Diseases; Humans; Pharmacology; Typhoid Fever; Typhoid-Paratyphoid Vaccines

Topics: Cardiovascular Agents; Coronary Disease; Ergonovine; Ergot Alkaloids; Heart Diseases; Humans; Nitrites; Nitroglycerin; Oxytocics

Topics: Adrenal Cortex Hormones; Cardiovascular Agents; Glucocorticoids; Heart Diseases

Topics: Anti-Arrhythmia Agents; Cardiotonic Agents; Cardiovascular Agents; Digitalis; Heart Diseases; Humans

Topics: Anti-Arrhythmia Agents; Cardiovascular Agents; Diuretics; Heart Diseases; Humans

Topics: Cardiotonic Agents; Cardiovascular Agents; Glycosides; Heart Diseases; Plant Extracts

Topics: Adrenal Cortex Hormones; Cardiovascular Agents; Diuretics; Heart Diseases; Humans; Pregnadienes

Topics: Cardiovascular Agents; Digitalis; Digitalis Glycosides; Heart Diseases; Iatrogenic Disease; Plant Extracts

Topics: Cardiotonic Agents; Cardiovascular Agents; Diuretics; Heart Diseases; Honey; Strophanthins