cardiovascular-agents and Arrhythmias--Cardiac

Cardiomyopathies represent an important cause of heart failure, often affecting young individuals, and have important implications for relatives. Genetic testing for cardiomyopathies is an established care pathway in contemporary cardiology practice. The primary cardiomyopathies where genetic testing is indicated are hypertrophic, dilated, arrhythmogenic, and restrictive cardiomyopathies, with left ventricular noncompaction as a variant phenotype. Early identification and initiation of therapies in patients with inherited cardiomyopathies allow for targeting asymptomatic and presymptomatic patients in stages A and B of the American College of Cardiology/American Heart Association classification of heart failure. The current approach for genetic testing uses gene panel-based testing with the ability to extend to whole-exome and whole-genome sequencing in rare instances. The central components of genetic testing include defining the genetic basis of the diagnosis, providing prognostic information, and the ability to screen and risk-stratify relatives. Genetic testing for cardiomyopathies should be coordinated by a multidisciplinary team including adult and pediatric cardiologists, genetic counsellors, and geneticists, with access to expertise in cardiac imaging and electrophysiology. A pragmatic approach for addressing genetic variants of uncertain significance is important. In this review, we highlight the indications for genetic testing in the various cardiomyopathies, the value of early diagnosis and treatment, family screening, and the care process involved in genetic counselling and testing.

Topics: Arrhythmias, Cardiac; Cardiomyopathies; Cardiovascular Agents; Defibrillators, Implantable; Ethnicity; Genetic Counseling; Genetic Predisposition to Disease; Genetic Testing; Heart Failure; Humans; Patient Education as Topic; Phenotype; Prognosis; Risk Assessment

Cardiac arrhythmias are a major source of mortality and morbidity. Unfortunately, their treatment remains suboptimal. Major classes of antiarrhythmic drugs pose a significant risk of proarrhythmia, and their side effects often outweigh their benefits. Therefore, implantable devices remain the only truly effective antiarrhythmic therapy, and new strategies of antiarrhythmic treatment are required. Ivabradine is a selective heart rate-reducing agent, an inhibitor of hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels, currently approved for treatment of coronary artery disease and chronic heart failure. In this review, we focus on the clinical and basic science evidence for the antiarrhythmic and proarrhythmic effects of ivabradine. We attempt to dissect the mechanisms behind the effects of ivabradine and indicate the focus of future studies.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Heart Rate; Humans; Ivabradine

Cardiotoxicity, defined as toxicity that affects the heart, is one of the most common adverse drug effects. Numerous drugs have been shown to have the potential to induce lethal arrhythmias by affecting cardiac electrophysiology, which is the focus of current preclinical testing. However, a substantial number of drugs can also affect cardiac function beyond electrophysiology. Within this broader sense of cardiotoxicity, this review discusses the key drug-protein interactions known to be involved in cardiotoxic drug response. We cover adverse effects of anticancer, central nervous system, genitourinary system, gastrointestinal, antihistaminic, anti-inflammatory, and anti-infective agents, illustrating that many share mechanisms of cardiotoxicity, including contractility, mitochondrial function, and cellular signaling.

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Arrhythmias, Cardiac; Cardiotoxicity; Cardiovascular Agents; Drug Development; Gastrointestinal Agents; Genitourinary Agents; Histamine Antagonists; Humans; Mitochondria, Heart; Myocardial Contraction; Myocardium; Myocytes, Cardiac; Neuroprotective Agents; Safety-Based Drug Withdrawals; Signal Transduction

Background Patients with mitral valve stenosis have increased heart rate. HR reduction is known as an important treatment and therapy strategy for patients with mitral valve stenosis. Aim of the review The aim of this systematic review and meta-analysis was to compare the efficacy of ivabradine versus beta-blockers in patients with mitral stenosis in sinus rhythm. Methods Randomized controlled trials were searched in Cochrane Library, PubMed, Web of Science, CRD, Scopus, and Google Scholar with no start time limitation and ending June 2018. Risk of bias across was assessed by the Cochrane Risk of Bias Assessment tool. Fixed effects models were used to combine the results and the mean difference with a 95% confidence interval. This meta-analysis was performed using Meta Package in R software. Results Five studies entered meta-analysis. The total number of patients treated with ivabradine and beta-blockers was 178 and 178 respectively. The results showed that the mean of maximum HR and HR at rest was lower at about 5.03 units and upper 4.32 units respectively with use of ivabradine compared with the use of beta-blockers. These values were statistically significant. Conclusion It seems that the efficacy of ivabradine is good in comparison with betablockers, but it still requires more clinical trials.

Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Cardiovascular Agents; Heart Rate; Humans; Ivabradine; Mitral Valve Stenosis; Randomized Controlled Trials as Topic; Treatment Outcome

Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiac Resynchronization Therapy; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Heart Failure; Heart Rate; Humans; Mineralocorticoid Receptor Antagonists; Neprilysin; Protease Inhibitors; Risk Factors; Stroke Volume; Treatment Outcome; Ventricular Function, Left

Gastrointestinal sensorimotor dysfunction underlies a wide range of esophageal, gastric, and intestinal motility and functional disorders that collectively constitute nearly half of all referrals to gastroenterologists. As a result, substantial effort has been dedicated toward the development of prokinetic agents intended to augment or restore normal gastrointestinal motility. However, the use of several clinically efficacious gastroprokinetic agents, such as cisapride, domperidone, erythromycin, and tegaserod, is associated with unfavorable cardiovascular safety profiles, leading to restrictions in their use.. The purpose of this review is to detail the cellular and molecular mechanisms that lead commonly to drug-induced cardiac arrhythmias, specifically drug-induced long QT syndrome, torsades de pointes, and ventricular fibrillation, to examine the cardiovascular safety profiles of several classes of prokinetic agents currently in clinical use, and to explore potential strategies by which the risk of drug-induced cardiac arrhythmia associated with prokinetic agents and other QT interval prolonging medications can be mitigated successfully.

Topics: Animals; Anti-Bacterial Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Gastrointestinal Agents; Gastrointestinal Motility; Humans; Long QT Syndrome

Heat shock proteins (HSPs) are an important family of protective proteins. They are involved actively in an array of cellular processes, including protective effects on the cardiovascular system in response to various stimuli. Increasing evidence shows that pharmacologic interventions that induce expression of HSPs may be a novel approach for the treatment of cardiovascular diseases. However, agents that induce expression of HSPs used previously are toxic or have harmful side effects, which limit their clinical application. Geranylgeranylacetone (GGA) is not only a widely used antiulcer agent in Asia, but also a nontoxic inducer of HSPs expression. It increases the expression of HSPs rapidly in the presence of ischemia, anoxia, oxidative stress, and toxicants, thereby having significant protective effects. The cardioprotective effects of GGA have been corroborated by experiments in vivo and in vitro. Importantly, several derivatives of GGA have been synthesized that have improved pharmaco-chemical and HSPs-boosting properties. In this review, the current knowledge and potential cardioprotective mechanisms of GGA are summarized comprehensively. We discuss the protective effects of GGA in cardiovascular diseases and myocardial injury induced by physical or chemical injury. Currently available information suggests that GGA could be employed as a novel pharmacologic intervention against cardiovascular disease.

Topics: Animals; Anti-Arrhythmia Agents; Apoptosis; Arrhythmias, Cardiac; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular System; Diterpenes; Endothelium, Vascular; Heat-Shock Proteins; Humans; Insulin Resistance; Myocardium; Oxidative Stress; Treatment Outcome

Topics: Arrhythmias, Cardiac; Cardiac Conduction System Disease; Cardiovascular Agents; Heart Conduction System; Humans; Perioperative Care; Treatment Outcome

The peak sodium current underlies excitability and conduction in heart muscle, but a late sodium current flowing after the peak contributes to maintaining and prolonging the action potential plateau, and also to intracellular sodium loading, which in turn increases intracellular calcium with consequent effects on arrhythmia and diastolic function. Late sodium current is pathologically increased in both genetic and acquired heart disease, making it an attractive target for therapy to treat arrhythmia, heart failure, and angina. This review provides an overview of the underlying bases for the clinical implications of late sodium current block.

Topics: Action Potentials; Angina Pectoris; Arrhythmias, Cardiac; Cardiovascular Agents; Electrophysiologic Techniques, Cardiac; Heart Failure; Humans; Sodium Channels

Drugs are widely used and highly effective in the treatment of heart disease. Nevertheless, in some instances, even drugs effective in a population display lack of efficacy or adverse drug reactions in individual patients, often in an apparently unpredictable fashion. This review summarizes the genomic factors now known to influence variability in responses to widely used cardiovascular drugs such as clopidogrel, warfarin, heparin and statins. Genomic approaches being used to discover new pathways in common cardiovascular diseases and thus potential new targets for drug development are described. Finally, the way in which this new information is likely to be used in an electronic medical record environment is discussed.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Clopidogrel; Genetic Variation; Genomics; Hematologic Agents; Heparin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pharmacogenetics; Ticlopidine; Warfarin

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

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

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

Mineralocorticoid receptor (MR) antagonism is a well-established treatment modality for patients with hypertension, heart failure, and left ventricular systolic dysfunction (LVSD) post-myocardial infarction (MI). There are emerging data showing potential benefits of MR antagonists in other cardiovascular conditions. Studies have shown association between MR activation and the development of myocardial fibrosis, coronary artery disease, metabolic syndrome, and cerebrovascular diseases. This review examines the preclinical and clinical data of MR antagonists for novel indications including heart failure with preserved ejection fraction (HFPEF), pulmonary arterial hypertension (PAH), arrhythmia, sudden cardiac death, valvular heart disease, metabolic syndrome, renal disease, and stroke. MR antagonists are not licensed for these conditions yet; however, emerging data suggest that indication for MR antagonists are likely to broaden; further studies are warranted.

Topics: Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Cardiovascular Diseases; Death, Sudden, Cardiac; Disease Progression; Heart Failure; Humans; Hypertension, Pulmonary; Mineralocorticoid Receptor Antagonists; Models, Biological; Off-Label Use; Receptors, Mineralocorticoid; Severity of Illness Index

Despite the revolutionary advancements in the past 3 decades in the treatment of ventricular tachyarrhythmias with device-based therapy, sudden cardiac death (SCD) remains an enormous public health burden. Survivors of SCD are generally at high risk for recurrent events. The clinical management of such patients requires a multidisciplinary approach from postresuscitative care to a thorough cardiovascular investigation in an attempt to identify the underlying substrate, with potential to eliminate or modify the triggers through catheter ablation and ultimately an implantable cardioverter-defibrillator (ICD) for prompt treatment of recurrences in those at risk. Early recognition of low left ventricular ejection fraction as a strong predictor of death and association of ventricular arrhythmias with sudden death led to significant investigation with antiarrhythmic drugs. The lack of efficacy and the proarrhythmic effects of drugs catalyzed the development and investigation of the ICD through several major clinical trials that proved the efficacy of ICD as a bedrock tool to detect and promptly treat life-threatening arrhythmias. The ICD therapy is routinely used for primary prevention of SCD in patients with cardiomyopathy and high risk inherited arrhythmic conditions and secondary prevention in survivors of sudden cardiac arrest. This compendium will review the clinical management of those surviving SCD and discuss landmark studies of antiarrhythmic drugs, ICD, and cardiac resynchronization therapy in the primary and secondary prevention of SCD.

Topics: Acute Coronary Syndrome; Arrhythmias, Cardiac; Cardiac Resynchronization Therapy; Cardiopulmonary Resuscitation; Cardiovascular Agents; Catheter Ablation; Clinical Trials as Topic; Death, Sudden, Cardiac; Defibrillators, Implantable; Disease Management; Electric Countershock; Electrocardiography; Heart Arrest; Humans; Multicenter Studies as Topic; Primary Prevention; Recurrence; Secondary Prevention; Survivors; Sympathectomy

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

Heart failure has become the cardiovascular epidemic of the century. The European Journal of Heart Failure is dedicated to the advancement of knowledge in the field of heart failure management. In 2012 and 2013, several pioneering scientific discoveries and paradigm-shifting clinical trials have been published. In the current paper, we will discuss the most significant novel insights into the pathophysiology, diagnosis, and treatment of heart failure that were published during this period. All relevant research areas are discussed, including pathophysiology, co-morbidities, arrhythmias, biomarkers, clinical trials, and device therapy, including left ventricular assist devices.

Topics: Arrhythmias, Cardiac; Biomarkers; Cardiovascular Agents; Clinical Trials as Topic; Defibrillators, Implantable; Heart Failure; Heart-Assist Devices; Humans

The autonomic nervous system plays an important role in the modulation of cardiac electrophysiology and arrhythmogenesis. Decades of research has contributed to a better understanding of the anatomy and physiology of cardiac autonomic nervous system and provided evidence supporting the relationship of autonomic tone to clinically significant arrhythmias. The mechanisms by which autonomic activation is arrhythmogenic or antiarrhythmic are complex and different for specific arrhythmias. In atrial fibrillation, simultaneous sympathetic and parasympathetic activations are the most common trigger. In contrast, in ventricular fibrillation in the setting of cardiac ischemia, sympathetic activation is proarrhythmic, whereas parasympathetic activation is antiarrhythmic. In inherited arrhythmia syndromes, sympathetic stimulation precipitates ventricular tachyarrhythmias and sudden cardiac death except in Brugada and J-wave syndromes where it can prevent them. The identification of specific autonomic triggers in different arrhythmias has brought the idea of modulating autonomic activities for both preventing and treating these arrhythmias. This has been achieved by either neural ablation or stimulation. Neural modulation as a treatment for arrhythmias has been well established in certain diseases, such as long QT syndrome. However, in most other arrhythmia diseases, it is still an emerging modality and under investigation. Recent preliminary trials have yielded encouraging results. Further larger-scale clinical studies are necessary before widespread application can be recommended.

Topics: Acupuncture Therapy; Animals; Arrhythmias, Cardiac; Atrial Fibrillation; Autonomic Nervous System; Cardiovascular Agents; Catheter Ablation; Cryosurgery; Death, Sudden, Cardiac; Disease Models, Animal; Electric Stimulation Therapy; Ganglia, Autonomic; Heart Conduction System; Heart Rate; Humans; Medulla Oblongata; Models, Cardiovascular; Models, Neurological; Spinal Cord; Vagus Nerve; Vagus Nerve Stimulation; Ventricular Fibrillation

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

Efforts to use gene therapy to create a biological pacemaker as an adjunct or replacement of electronic pacemakers have been ongoing for about 15 years. For the past decade, most of these efforts have focused on the hyperpolarization-activated cyclic nucleotide gated-(HCN) gene family of channels alone or in combination with other genes. The HCN gene family is the molecular correlate of the cardiac pacemaker current, If. It is a suitable basis for a biological pacemaker because it generates a depolarizing inward current primarily during diastole and is directly regulated by cyclic adenosine monophosphate (cAMP), thereby incorporating autonomic responsiveness. However, biological pacemakers based either on native HCN channels or on mutated HCN channels designed to optimize biophysical characteristics have failed to attain the desired basal and maximal physiological heart rates in large animals. More recent work has explored dual gene therapy approaches, combining an HCN variant with another gene to reduce outward current, increase an additional inward current, or enhance cAMP synthesis. Several of these dual gene therapy approaches have demonstrated appropriate basal and maximal heart rates with little or no reliance on a backup electronic pacemaker during the period of study. Future research, besides examining the efficacy of other gene combinations, will need to consider the additional issues of safety and persistence of the viral vectors often used to deliver these genes to a specific cardiac region.

Topics: Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Electrophysiologic Techniques, Cardiac; Genetic Therapy; Heart; Heart Rate; Humans; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Sinoatrial Node

Cardiac arrhythmias comprise of a heterogeneous group of disorders which manifest in a wide range of clinical presentations. They can be associated with underlying cardiac disease and portend a grave prognosis, with some arrhythmias being rapidly fatal. Other arrhythmias, however are relatively benign and can be asymptomatic or may be a mere inconvenience for the patient. All primary care physicians can expect to encounter some forms of arrhythmias during the course of their practice. This review article provides a brief overview of the commonly seen tachyarrhythmias for the general practitioner and provides relevant updates on the recent developments in our understanding of their mechanisms and management.

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Flutter; Cardiovascular Agents; Catheter Ablation; Electric Countershock; Electrocardiography; Heart Ventricles; Humans; Risk Factors; Tachycardia

Topics: Adaptation, Psychological; Arrhythmias, Cardiac; Automobile Driving; Cardiac Pacing, Artificial; Cardiovascular Agents; Clinical Trials as Topic; Combined Modality Therapy; Defibrillators, Implantable; Disease Management; Electric Countershock; Electric Injuries; Equipment Failure; Humans; Monitoring, Physiologic; Mood Disorders; Multicenter Studies as Topic; Pacemaker, Artificial; Patient Acceptance of Health Care; Patient Education as Topic; Psychotherapy; Quality of Life; Sports; Stress, Psychological; Telemedicine; Terminal Care; Withholding Treatment

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

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

Adenosine receptor stimulation has negative inotropic and dromotropic actions, reduces cardiac ischemia-reperfusion injury and remodeling, and prevents cardiac arrhythmias. In the vasculature, adenosine modulates vascular tone, reduces infiltration of inflammatory cells and generation of foam cells, and may prevent the development of atherosclerosis as a result. Modulation of insulin sensitivity may further add to the anti-atherosclerotic properties of adenosine signaling. In the kidney, adenosine plays an important role in tubuloglomerular feedback and modulates tubular sodium reabsorption. The challenge is to take advantage of the beneficial actions of adenosine signaling while preventing its potential adverse effects, such as salt retention and sympathoexcitation. Drugs that interfere with adenosine formation and elimination or drugs that allosterically enhance specific adenosine receptors seem to be most promising to meet this challenge.

Topics: Adenosine; Animals; Arrhythmias, Cardiac; Atherosclerosis; Cardiovascular Agents; Cardiovascular Diseases; Humans; Insulin; Kidney; Receptors, Purinergic P1; Reperfusion Injury; Signal Transduction

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Continuity of Patient Care; Diagnostic Techniques, Cardiovascular; Electric Stimulation Therapy; Emergency Medical Services; Follow-Up Studies; Heart Block; Heart Conduction System; Humans; Models, Biological

Hyperpolarization and Cyclic Nucleotide (HCN) -gated channels represent the molecular correlates of the "funny" pacemaker current (I(f)), a current activated by hyperpolarization and considered able to influence the sinus node function in generating cardiac impulses. HCN channels are a family of six transmembrane domain, single pore-loop, hyperpolarization activated, non-selective cation channels. This channel family comprises four members: HCN1-4, but there is a general agreement to consider HCN4 as the main isoform able to control heart rate. This review aims to summarize advanced insights into the structure, function and cellular regulation of HCN channels in order to better understand the role of such channels in regulating heart rate and heart function in normal and pathological conditions. Therefore, we evaluated the possible therapeutic application of the selective HCN channels blockers in heart rate control.

Topics: Animals; Arrhythmias, Cardiac; Biological Clocks; Cardiovascular Agents; Circadian Rhythm; Cyclic Nucleotide-Gated Cation Channels; Disease Models, Animal; Heart Rate; Humans; Membrane Transport Modulators; Mice; Mice, Knockout; Mutation; Sinoatrial Node

The late Na current is of pathophysiological importance for the heart. Ranolazine is an innovative anti-ischemic and antianginal agent that inhibits the late Na current, thereby reducing the Na-dependent Ca-overload, which improves diastolic tone and oxygen handling during myocardial ischemia. In addition, ranolazine seems to exert beneficial effects on diastolic cardiac function. Moreover, there are experimental and clinical data about its antiarrhythmic properties. A beneficial atrial selectivity of ranolazine has been suggested that may be helpful for the treatment of atrial fibrillation. The purpose of this review article is to discuss possible future clinical indications based on novel experimental and preclinical results and the significance of the available data.

Topics: Acetanilides; Action Potentials; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Calcium; Cardiovascular Agents; Cations; Diastole; Enzyme Inhibitors; Heart Failure; Heart Failure, Diastolic; Humans; Myocardial Contraction; NAV1.5 Voltage-Gated Sodium Channel; Piperazines; Ranolazine; Sodium; Sodium-Calcium Exchanger

Studies have suggested that increasing whole body blood flow and oxygen delivery around the time of surgery reduces mortality, morbidity and the expense of major operations.. To describe the effects of increasing perioperative blood flow using fluids with or without inotropes or vasoactive drugs. Outcomes were mortality, morbidity, resource utilization and health status.. We searched CENTRAL (The Cochrane Library 2012, Issue 1), MEDLINE (1966 to March 2012) and EMBASE (1982 to March 2012). We manually searched the proceedings of major conferences and personal reference databases up to December 2011. We contacted experts in the field and pharmaceutical companies for published and unpublished data.. We included randomized controlled trials with or without blinding. We included studies involving adult patients (aged 16 years or older) undergoing surgery (patients having a procedure in an operating room). The intervention met the following criteria. 'Perioperative' was defined as starting up to 24 hours before surgery and stopping up to six hours after surgery. 'Targeted to increase global blood flow' was defined by explicit measured goals that were greater than in controls, specifically one or more of cardiac index, oxygen delivery, oxygen consumption, stroke volume (and the respective derived indices), mixed venous oxygen saturation (SVO(2)), oxygen extraction ratio (0(2)ER) or lactate.. Two authors independently extracted the data. We contacted study authors for additional data. We used Review Manager software.. We included 31 studies of 5292 participants. There was no difference in mortality: 282/2615 (10.8%) died in the control group and 238/2677 (8.9%) in the treatment group, RR of 0.89 (95% CI 0.76 to 1.05, P = 0.18). However, the results were sensitive to analytical methods and the intervention was better than control when inverse variance or Mantel-Haenszel random-effects models were used, RR of 0.72 (95% CI 0.55 to 0.95, P = 0.02). The results were also sensitive to withdrawal of studies with methodological limitations. The rates of three morbidities were reduced by increasing global blood flow: renal failure, RR of 0.71 (95% CI 0.57 to 0.90); respiratory failure, RR of 0.51 (95% CI 0.28 to 0.93); and wound infections, RR of 0.65 (95% CI 0.51 to 0.84). There were no differences in the rates of nine other morbidities: arrhythmia, pneumonia, sepsis, abdominal infection, urinary tract infection, myocardial infarction, congestive cardiac failure or pulmonary oedema, or venous thrombosis. The number of patients with complications was reduced by the intervention, RR of 0.68 (95% CI 0.58 to 0.80). Hospital length of stay was reduced in the treatment group by a mean of 1.16 days (95% CI 0.43 to 1.89, P = 0.002). There was no difference in critical care length of stay. There were insufficient data to comment on quality of life and cost effectiveness.. It remains uncertain whether increasing blood flow using fluids, with or without inotropes or vasoactive drugs, reduces mortality in adults undergoing surgery. The primary analysis in this review (mortality at longest follow-up) showed no difference between the intervention and control, but this result was sensitive to the method of analysis, the withdrawal of studies with methodological limitations, and is dominated by a single large RCT. Overall, for every 100 patients in whom blood flow is increased perioperatively to defined goals, one can expect 13 in 100 patients (from 40/100 to 27/100) to avoid a complication, 2/100 to avoid renal impairment (from 8/100 to 6/100), 5/100 to avoid respiratory failure (from 10/100 to 5/100), and 4/100 to avoid postoperative wound infection (from 10/100 to 6/100). On average, patients receiving the intervention stay in hospital one day less. It is unlikely that the intervention causes harm. The balance of current evidence does not support widespread implementation of this approach to reduce mortality but does suggest that complications and duration of hospital stay are reduced.

Topics: Adult; Arrhythmias, Cardiac; Blood Circulation; Cardiovascular Agents; Humans; Length of Stay; Oxygen Consumption; Plasma Substitutes; Postoperative Complications; Randomized Controlled Trials as Topic; Renal Insufficiency; Respiratory Insufficiency; Surgical Procedures, Operative; Surgical Wound Infection

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

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

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

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

Safe pharmacotherapy and prevention of arrhythmia is an urgent problem of modern cardiology. Essential micronutrients such as omega-3 polyunsaturated fatty acids (-3 PUF-) significantly contribute to the metabolic processes in cardiomyocytes and cardiac conduction system. This article presents a systematic analysis of anti-arrhythmic effects of omega-3 PUFA and of standardized ethyl esters of omega-3 PUFA. The currently available data indicate two fundamentally different molecular mechanisms of anti-arrhythmic effects: "slow" and "fast" types. Formulation of fundamental prospects of bioinformatic studies of molecular effects of anti-arrhythmic action of omega-3 PUF-s is presented.

Topics: Arachidonic Acid; Arrhythmias, Cardiac; Biotransformation; Cardiovascular Agents; Clinical Trials as Topic; Cytochromes; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Heart Conduction System; Humans; Ion Channels; Micronutrients; Myocytes, Cardiac; Receptors, Eicosanoid; Receptors, Prostaglandin

Cardiovascular diseases are among the leading causes of death in the developed world. Developing novel therapies for diseases like heart failure is crucial, but this is hampered by the high attrition rate in drug development. The withdrawal of drugs at the final hurdle of approval is mostly because of their unpredictable effects on normal cardiac rhythm. The advent of cardiac computational modeling in the last 5 decades has aided the understanding of heart function significantly. Recently, these models increasingly have been applied toward designing and understanding therapies for cardiac disease. This article will discuss how cellular models of electrophysiology, cell signaling, and metabolism have been used to investigate pharmacologic therapies for cardiac diseases including arrhythmia, ischemia, and heart failure.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Computer Simulation; Drug Discovery; Electrophysiological Phenomena; Heart; Heart Failure; Humans; Ion Channels; Ischemia; Models, Cardiovascular; Signal Transduction

In addition to their therapeutic effect, all drugs have unwanted effects. For the purpose of this MiniReview, unwanted drug effects will be discussed as either predictable, dose-dependent effects, or as less predictable events which only occur in patients pre-disposed to unwanted drug reactions when confronted with specific situations. While clinicians have long been using biomarkers to identify patients prone to less predictable unwanted drug effects, emerging data clearly suggest that such effects are often a consequence of interactions between drug effects, drug metabolism, an individual, at times genetically conferred pre-disposition to the interaction, and transient pre-disposing factors. This paper describes general principles of predictable and less predictable unwanted drug effects and discusses the complex interplay of genetic and acquired pre-disposing and precipitating factors for such effects using the example of ventricular pro-dysrhythmia. The latter, an important unwanted effect of many drugs, is a common yet not fully understood less predictable cardiac drug effect. Understanding the mechanisms of ventricular pro-dysrhythmia may allow to predict this unwanted drug effect better, and to identify novel markers for such events in the future.

Topics: Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Dose-Response Relationship, Drug; Electrocardiography; Humans; Long QT Syndrome; Precipitating Factors; Prognosis; Risk Factors; Sodium Channel Blockers; Torsades de Pointes

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Clinical Trials as Topic; Dietary Supplements; Evidence-Based Medicine; Fatty Acids, Omega-3; Humans; Myocardial Infarction; Treatment Outcome

Mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophies. In addition to muscle disease, there nearly always is an associated cardiomyopathy in Duchenne or Becker muscular dystrophy. In these muscular dystrophies, the severity of cardiomyopathy and congestive heart failure may not parallel the severity of skeletal muscle disease. Loss of normal dystrophin function in the heart produces four-chamber dilation and reduction in left ventricular function that develop after the onset of muscle weakness. Arrhythmias affecting both atrial and ventricular rhythms occur and may be life threatening. The degree to which hypoventilation and pulmonary dysfunction are present also directly affect cardiac function in muscular dystrophy. Care guidelines recently were issued to outline surveillance and treatment strategies for the younger patient with Duchenne muscular dystrophy. Herein, we review those guidelines, and additionally, provide recommendations for monitoring and treating cardiac disease in the populations of advanced Duchenne and Becker muscular dystrophies.

Topics: Arrhythmias, Cardiac; Cardiac Resynchronization Therapy; Cardiomyopathy, Dilated; Cardiovascular Agents; Defibrillators, Implantable; Disease Progression; Dystrophin; Genes, X-Linked; Heart Transplantation; Humans; Male; Monitoring, Physiologic; Muscular Dystrophy, Duchenne; Myocardium

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

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

Despite the FDA guidelines for studies to be performed to rule out potential cardiac toxicity, many drugs have nevertheless entered the market only to be later withdrawn from the market owing to cardiac toxicity. Cardiac toxicity may result from drugs causing impaired function or death of cardiomyocytes, valvular damage, myocardial ischemia and/or ventricular arrhythmias. Negative cardiovascular events have been implicated in 28% of drug withdrawals in the USA. The significance for patients, regulators and the pharmaceutical industry is immense.. We address whether a more rigorous and integrative approach is needed for cardiovascular safety screening of all new drug candidates. Furthermore, we will present a cardionomics approach that looks at several in vitro and in vivo models that can be applied to all drugs independent of category, therapeutic area or class.. We present examples of drugs demonstrating cardiac toxicity and provide an in-depth review of how calcium homeostasis may be a unifying theme in clinically observed cardiotoxic events. We introduce a cardionomics approach that detects clinical cardiac toxicity early in the drug discovery process, thus, preventing costly late attrition.. The consequences of a failure to detect potential cardiovascular safety issues before clinical launch can have an enormous cost for the pharmaceutical industry, when major drugs are withdrawn due to lawsuits as well as loss of time and resources. An integrated cardionomics approach may reduce the risk of drug withdrawals as a result of unexpected clinical cardiac safety issues.

Topics: Animals; Arrhythmias, Cardiac; Biomedical Research; Cardiovascular Agents; Cardiovascular Diseases; Drug Evaluation, Preclinical; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmaceutical Preparations

Cocaine is a powerful stimulant that gives users a temporary sense of euphoria, mental alertness, talkativeness, and a decreased need for food and sleep. Cocaine intoxication is the most frequent cause of drug-related death reported by medical examiners in the US, and these events are most often related to the cardiovascular manifestations of the drug. Once playing a vital role in medicine as a local anesthetic, decades of research have established that cocaine has the ability to cause irreversible structural damage to the heart, greatly accelerate cardiovascular disease, and initiate sudden cardiac death. Although pathologic findings are often reported in the literature, few images are available to support these findings, and reviews of cocaine cardiopathology are rare. We describe the major pathologic findings linked to cocaine abuse in earlier research, their underlying mechanisms, and the treatment approaches currently being used in this patient population. A MEDLINE search was conducted to identify all English language articles from January 2000 to June 2008 with the subject headings and key words 'cocaine', 'heart', 'toxicity', and 'cardiotoxicity'. Epidemiologic, laboratory, and clinical studies on the pathology, pathophysiology, and pharmacology of the effects of cocaine on the heart were reviewed, along with relevant treatment options. Reference lists were used to identify earlier studies on these topics, and related articles from Google Scholar were also included. There is an established connection between cocaine use and myocardial infarction (MI), arrhythmia, heart failure, and sudden cardiac death. Numerous mechanisms have been postulated to explain how cocaine contributes to these conditions. Among these, cocaine may lead to MI by causing coronary artery vasoconstriction and accelerated atherosclerosis, and by initiating thrombus formation. Cocaine has also been shown to block K+ channels, increase L-type Ca2+ channel current, and inhibit Na+ influx during depolarization, all possible causes for arrhythmia. Additionally, cocaine use has been associated with left ventricular hypertrophy, myocarditis, and dilated cardiomyopathy, which can lead to heart failure if drug use is continued. Certain diagnostic tools, including ECG and serial cardiac markers, are not as accurate in identifying MI in cocaine users experiencing chest pain. As a result, clinicians should be suspicious of cocaine use in their differential diagnosis of chest pain, especia

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Cocaine; Death, Sudden, Cardiac; Heart; Heart Failure; Humans; Myocardial Infarction; Myocardium; Practice Guidelines as Topic

Following a series of high profile withdrawals from the market, the ability of medications to induce potentially fatal arrhythmias is a significant problem facing the pharmaceutical industry. Current preclinical cardiac safety assays are based on the assumption that blockade of a single repolarizing K(+) channel alone precipitates drug-induced arrhythmias, however, current findings point to a range of more complex arrhythmogenic mechanisms. This review begins by exploring clinical findings and potential mechanisms underlying drug-induced sudden cardiac death and then goes on to assess current and explore future strategies to detect cardiotoxicity at the preclinical stage.

Topics: Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Death, Sudden, Cardiac; Drug Industry; Humans; Long QT Syndrome; Potassium Channel Blockers

Topics: Anti-Bacterial Agents; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Cardiac Surgical Procedures; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Catheter Ablation; Death, Sudden, Cardiac; Endocarditis; Humans; Treatment Outcome; Ventricular Outflow Obstruction

The concept of reperfusion injury has been a subject of intense debate. Some researchers believe that the entire injury develops during the ischemic period, whereas others argue that blood reflow extends tissue injury due to the release of oxygen-derived free radicals, an inflammatory reaction involving influx of various populations of immune cell, and dysregulation of intracellular and particularly mitochondrial calcium concentration. Mitochondrial calcium overload in the presence of oxygen-derived free radicals can result in the opening of the mitochondrial permeability transition pore (mPTP), which further compromises cellular energetics. The resultant low ATP and altered ion homeostasis lead to a rupture of the plasma membrane and cell death. Mitochondria have long been proposed as one of the main players in cell death, since the mitochondria are central to synthesis of both ATP and the formation of oxygen-derived free radicals. These mechanisms are centered on mitochondrial calcium overload as a key component of cell death. Pharmacological strategies that are cardioprotective attempt to reduce mitochondrial calcium overload to decrease the likelihood of arrhythmias and cardiac dysfunction elicited by reperfusion.

Topics: Adenosine Triphosphate; Animals; Apoptosis; Arrhythmias, Cardiac; Calcium; Cardiovascular Agents; Humans; Membrane Potential, Mitochondrial; Mitochondria, Heart; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Myocardial Reperfusion Injury; Reactive Oxygen Species; Signal Transduction; Time Factors

Underlying causes of ventricular tachycardia (VT) or complex ventricular arrhythmias (VA) should be treated if possible. This may include beta-adrenergic blockade radiofrequency catheter ablation and automatic implantable cardioverter-defibrillators. The ACC/AHA Class I indications for an AICD are discussed. Patients with AICDs should be treated with biventricular pacing, not with dual-chamber rate-responsive pacing at a rate of 70/minute.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium Channel Blockers; Cardiovascular Agents; Catheter Ablation; Defibrillators, Implantable; Humans; Tachycardia, Ventricular; Ventricular Fibrillation

Sodium (Na) channels are essential for cardiac electrical activity. Cardiac Na channel dysfunction, inherited or acquired, can induce life-threatening conduction and arrhythmia disorders. Inherited Na channel dysfunction may put affected patients at a greater risk for these complications when channel-modifying drugs are prescribed. This study addressed pharmacogenetic effects in three well-described Na channel-related diseases: long QT syndrome type 3, Brugada syndrome and inherited cardiac conduction disease. A review of the currently available literature on cardiac Na channel-modulating drugs was undertaken. An overview is given of the known risks of development of the previously mentioned complications of commonly prescribed drugs in patients affected with Na channel-related diseases and the underlying mechanisms.

Topics: Action Potentials; Arrhythmias, Cardiac; Brugada Syndrome; Cardiovascular Agents; Electrocardiography; Genetic Predisposition to Disease; Humans; Long QT Syndrome; Mutation; Myocardium; Pedigree; Pharmacogenetics; Protein Conformation; Risk Factors; Sodium Channels

Topics: Adrenergic beta-Antagonists; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Bradycardia; Calcium Channel Blockers; Cardiovascular Agents; Humans; Tachycardia

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

Omega-3 fatty acid therapy shows great promise in the secondary prevention of coronary artery disease. A meta-analysis of recent omega-3 trials shows reductions of coronary heart disease mortality of 36% (95% CI, 20%-50%; P<0.001) and total mortality of 17% (95% CI, 0%-32%; P=0.046). Some of the potential mechanisms for cardiovascular protection include a reduction in cardiac arrhythmias and plaque stabilization. Since the publication of the landmark GISSI-Prevenzione trial, there have been three major intermediate cardiovascular endpoint studies in patients with implantable cardioverter defibrillators (ICDs) and one large trial, the Japan EPA Lipid Interventional Study (JELIS) trial, which involved 18,645 Japanese patients in primary and secondary prevention. The three studies with ICD patients have been mixed, with favorable trends toward reduction in the incidence of ventricular arrhythmias in some but not all of the studies. Results of the recent JELIS trial in a Japanese population already consuming a high intake of omega-3 fatty acids showed a 19% risk reduction in major coronary events. Most of the reductions were in unstable angina and nonfatal coronary events, but not in sudden death and cardiovascular mortality. The totality of evidence suggests greater benefits with omega-3 fatty acids in secondary prevention than primary prevention and in populations consuming low amounts of omega-3 fatty acids.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Coronary Disease; Defibrillators, Implantable; Fatty Acids, Omega-3; Humans; Meta-Analysis as Topic; Randomized Controlled Trials as Topic

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

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

Several clinical studies demonstrate the importance of the heart rate for the cardiovascular morbidity and mortality. Over the last 50 years, some thought has been given to those substances that selectively reduce the heart rate. It is now recognized that I(f) ion channels of the sinus node play a major role in the automatism and modulation of the heart rate. Substances that selectively reduce the heart rate should decrease myocardial oxygen consumption and increase oxygen delivery via the prolonged diastolic coronary perfusion. Direct inotropic effects, however, are unlikely. In principle, anti-anginal and anti-ischemic effects of specific bradycardic substances can be expected. The clinical experience with some of the former bradycardic substances has not been sufficiently convincing. The more recent ivabradine (Procoralan presents an exception to this, as it successfully completed a clinical program for the treatment of chronically stable angina pectoris. In this review article, specific bradycardic substances (= I(f) channel inhibitors) are presented together with the corresponding experimental and clinical studies. The studies were selected against the background of the efficacy of I(f) channel inhibitors in the therapy of cardiovascular disease. As only ivabradine has completed a study on 5,000 patients, the discussion on that particular I(f) channel inhibitor is somewhat extensive. In addition, prospective possibilities and limitations of bradycardic substances are presented.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Benzazepines; Cardiotonic Agents; Cardiovascular Agents; Clonidine; Coronary Artery Disease; Humans; Isoindoles; Ivabradine; Phthalimides; Practice Guidelines as Topic; Practice Patterns, Physicians'

Identified in 2000, short QT syndrome is an electrical disease of the heart characterised as a channelopathy. At first considered extremely rare, families with this disease have been found in Brazil, Finland, Germany, Spain, the Netherlands, France, Turkey, Italy and the US. The focus of the paper is to present a current review of short QT syndrome, as well as providing an overview upon the potential molecular target-based strategies for management of this very deadly disease. Abnormalities in three different potassium channels have been recognised as the cause of the disease and targets for therapy will be discussed for each potassium channel individually. In addition to pharmacological strategies, gene therapy with transfer of genes coding for specific ion channel subunits or regulatory proteins are discussed.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Drug Delivery Systems; Genetic Therapy; Humans; Long QT Syndrome; Potassium Channels, Voltage-Gated

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

It is noteworthy that drugs having a significant impact in preventing arrhythmias (atrial or ventricular) are those with no direct specific antiarrhythmic electrophysiologic properties. Specifically, drugs able to interfere with the renin-angiotensin system and the n-3 fatty acids seem to play a relevant role as antiarrhythmics, even if they do not act in the typical manner. Angiotensin-converting enzyme (ACE) inhibitors decrease the incidence of arrhythmias in patients with decreased left ventricular function. The main reduction is linked to a decrease of ventricular arrhythmias, while several studies have suggested that ACE-inhibitors may also decrease the burden of atrial fibrillation. Furthermore, many of angiotensin receptor blockers and spironolactone have been shown to have antiarrhythmic properties. n-3 polyunsaturated fatty acids (PUFAs) are known to be antiarrhythmic as well. Their effects on the fast voltage-dependent sodium current I(NA), inhibition of I(Ca2+) and the K+ channel modulation explain their antiarrhythmic properties. For these reasons the renin-angiotensin system blockade and the n-3 PUFA intake may provide simple and safe protection from cardiac arrhythmias.

Topics: Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Cardiovascular Agents; Fatty Acids, Omega-3; Humans; Mineralocorticoid Receptor Antagonists; Receptors, Angiotensin

Topics: Airway Obstruction; Algorithms; Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Cardiopulmonary Resuscitation; Cardiovascular Agents; Cricoid Cartilage; Electric Countershock; Europe; Heart Arrest; Hospitalization; Humans; Intubation, Intratracheal

The association between chronic kidney disease and cardiovascular death is accounted for, in part, by higher rates of serious arrhythmias. Research shows an independent relationship between worsened renal function and atrial fibrillation, heart block, ventricular tachycardia, ventricular fibrillation, and asystole. These higher rates also associate with underlying structural heart disease including left ventricular hypertrophy, cardiac fibrosis, valvular disease, and left ventricular systolic and diastolic dysfunction. In addition, chronic intermittent ischemia is implicated in the arrhythmias observed during hemodialysis. The superimposed conditions of acidosis and fluxes in both potassium and magnesium also contribute to higher rates of arrhythmias. Baseline estimated glomerular filtration rate is linked to worsened outcomes and increased defibrillation thresholds in patients receiving implantable cardioverter defibrillators. Preventive strategies include meticulous management of electrolytes, baseline treatment for cardiovascular disease, and when indicated, implantable cardioverter defibrillators. Future research into the mechanisms and prevention of sudden cardiac death in patients with chronic kidney disease is warranted.

Topics: Adrenergic beta-Antagonists; Arrhythmias, Cardiac; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Heart Function Tests; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Kidney Function Tests; Outcome Assessment, Health Care; Risk Factors

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

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disease characterized by unexplained left ventricular hypertrophy, typically involving the interventricular septum. Hypertrophy may be present in infants, but commonly develops during childhood and adolescence. Management of children with HCM aims to provide symptomatic relief and prevention of sudden death, which is the primary cause of death. Unfortunately, no randomized comparative trials to date have assessed different treatment options in HCM. Medical treatment with negative inotropic agents (beta-adrenoceptor antagonists [beta-blockers], verapamil) is the first therapeutic choice in all symptomatic patients. Beta-blockers also appear to have prognostic merit in children. Surgical myectomy is effective in reducing symptoms in children with left ventricular (LV) obstruction who are unresponsive to medical treatment, although a repeat operation may be needed in a substantial proportion of patients due to relapse of LV obstruction. The recently introduced percutaneous septal ablation can also be regarded as a feasible alternative in this cohort. Technical limitations of both invasive therapeutic options should be carefully considered, preferably in experienced centers. Results of recent randomized trials indicate that dual chamber pacing, once considered a therapeutic option for patients with HCM, should only be used as treatment for conduction abnormalities. Regular clinical risk stratification for sudden death is of vital importance for the prevention of sudden death in young patients. Familial history of sudden death at a young age, LV hypertrophy >3 cm, unexplained syncope, nonsustained ventricular tachycardia in Holter monitoring, and abnormal blood pressure response during exercise are currently considered clinical risk factors for sudden death. Each factor has a low positive predictive accuracy, but patients having two or more of these risk factors are deemed as high risk. Secondary prevention of sudden death in patients successfully resuscitated from cardiac arrest and/or sustained ventricular tachycardia warrants treatment with an implantable cardioverter defibrillator (ICD). Primary prevention of sudden death in patients considered to be at high risk should aim at the management of obvious arrhythmogenic mechanisms (paroxysmal atrial fibrillation, sustained monomorphic ventricular tachycardia, conduction system disease, accessory pathway, myocardial ischemia), and the prevention and/or

Topics: Adrenergic beta-Antagonists; Amiodarone; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium Channel Blockers; Cardiac Pacing, Artificial; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Catheter Ablation; Child; Death, Sudden, Cardiac; Endocarditis; Humans; Risk Factors

Topics: Acute Disease; Arrhythmias, Cardiac; Cardiovascular Agents; Hemodynamics; Humans

Topics: Arrhythmias, Cardiac; Cardiomyopathy, Hypertrophic, Familial; Cardiovascular Agents; Death, Sudden, Cardiac; Dyspnea; Heart Septum; Humans; Hypertrophy, Left Ventricular; Pacemaker, Artificial; Prevalence

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

Chronic heart failure (CHF) is a life threatening disease with an enormous medical requirement. Approximately 15 million people worldwide suffer from CHF. The prevalence will inevitably increase due to the ageing population. Nevertheless, current treatment options based on angiotensin-converting enzyme inhibitors and beta-adrenergic receptor antagonists merely slow progression of the disease. Novel treatment concepts based on new therapeutic targets must have the capability to reverse the severity of this disease. This review, focusing on the emerging targets in the most promising therapeutic areas for the treatment of CHF, will be divided into two parts. In Part I, disease concepts such as altered calcium handling and ion channel activity, pathophysiological hypertrophy and inefficient cardiac metabolism are discussed. Validation status and potential therapeutic value for new targets in each research field is given by summarising the results of in vitro and in vivo studies.

Topics: Animals; Anti-Arrhythmia Agents; Antihypertensive Agents; Arrhythmias, Cardiac; Calcium Channel Blockers; Calcium Channels; Calcium Signaling; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Energy Metabolism; Fatty Acids; Heart Failure; Humans; Ion Channels; MAP Kinase Signaling System; Mice; Muscle Proteins; PPAR alpha; Rats; Transcription Factors

Topics: Algorithms; Arrhythmias, Cardiac; Cardiovascular Agents; Coronary Angiography; Death, Sudden, Cardiac; Defibrillators, Implantable; Diagnosis, Differential; Electrocardiography; Heart Failure; Humans; Randomized Controlled Trials as Topic; Risk Assessment

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

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

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

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

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

Several in vitro and in vivo investigations have provided data supporting the existence of M cells in the deep subepicardial layers of the ventricles in a number of species. Characterized by unique electrophysiological and pharmacological features, this population of cells is regarded to have a significant role in creating dispersion of repolarization in the ventricular wall and thus contribute importantly to arrhythmogenesis, in particular to intramural reentry and triggered activity. Focusing on M cells, the authors summarize recent findings and concepts concerning the pharmacological heterogeneity of different cell and tissue types found within the ventricles and explore how these differences may contribute to electrocardiographic manifestations. On the basis of literary data and of their own results they conclude that studying the electrical and pharmacological inhomogeneity within the ventricular wall may provide a better understanding of the pathophysiological processes that give rise to cardiac rhythm disturbances and the mechanisms by which antiarrhythmic agents act to suppress and in some cases aggravate arrhythmias.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Electrophysiology; Heart Ventricles; In Vitro Techniques; Ion Transport; Ventricular Function

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

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

Until quite recently, the cardiodepressant actions of adenosine were widely accepted. A nucleoside that produces negative chronotropic and ionotropic effects, adenosine, has been used clinically as the drug of choice for terminating supraventricular (atrioventricular node) tachycardia and is likely to play an important part in regulating arrhythmogenic activity as an endogenous antiarrhythmic metabolite. Despite this, recent experimental data, particularly resulting from in vitro studies using animal models, have shown a paradoxical excitable action of adenosine in the heart. In this article, Amir Pelleg and Steven Kutalek present the reasons why they continue to believe that any excitatory actions of adenosine in the heart are clinically irrelevant.

Topics: Adenosine; Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Clinical Trials as Topic; Depression, Chemical; Heart; Humans; Myocardial Contraction

This article reviews the critical resuscitations necessary during prehospital and emergency department treatment of cardiac arrest. Standard therapy for cardiac arrest rhythms is presented. Novel pharmacologic agents, types of cardiopulmonary resuscitation, and circulatory-assist devices are discussed.

Topics: Adult; Algorithms; Arrhythmias, Cardiac; Cardiovascular Agents; Child; Emergency Medical Services; Heart Arrest; Hemodynamics; Humans; Intubation, Intratracheal; Monitoring, Physiologic; Physical Examination; Reperfusion Injury; Respiration; Respiration, Artificial; Resuscitation

Elderly patients have a significantly higher mortality and morbidity compared with younger patients in the postmyocardial infarction period and thus, with the appropriate management have a greater potential for benefit compared with younger patients. It has been shown in the large randomized trials that elderly patients with acute myocardial infarction benefit significantly from administration of beta-blocking agents and angiotensin-converting enzyme inhibitors. Aspirin and warfarin sodium (Coumadin) have been shown to benefit patients of all age groups. Secondary prevention with cessation of smoking, use of lipid-lowering agents, treatment of hypertension, and estrogen therapy in the postmenopausal woman have been shown to be effective. Elderly patients, therefore, who are free of general noncardiac disability and who can be expected to live meaningful lives should be offered a comprehensive program to reduce their cardiac morbidity and mortality after discharge following acute myocardial infarction.

Topics: Adrenergic beta-Antagonists; Aged; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Arrhythmias, Cardiac; Aspirin; Calcium Channel Blockers; Cardiovascular Agents; Estrogens; Female; Humans; Hyperlipidemias; Hypertension; Male; Myocardial Infarction; Risk Factors; Smoking

While post-myocardial infarct patients with frequent ventricular premature contractions or nonsustained ventricular tachycardia (NSVT) are at an increased risk of sudden arrhythmic death, the empirical use of antiarrhythmic agents for such patients is no longer justified after the results of the Cardiac Arrhythmia Suppression Trial. A series of major breakthroughs in the design and clinical application of the implantable cardioverter defibrillator (ICD) have taken place over the past two decades since its invention by M Mirowski. Although there is a general consensus for the effectiveness of the ICD therapy in aborting sudden arrhythmic death, it is unknown whether the use of the ICD therapy results in prolonged survival. Three randomized clinical trials directed to the survivors of cardiac arrest due to ventricular tachycardia (VT) or ventricular fibrillation (VF) are currently in progress, comparing the ICD therapy with drug therapy (amiodarone, beta blockers, and sotalol). Already over seventeen hundred patients have been randomized and followed in these three clinical trials. All three trials continue currently indicating no emergence of statistically significant differences in total mortality between the two therapy groups. Prophylactic application of the ICD has been studied in the MADIT (Multicenter Automatic Defibrillator Implantation Trial)--the first randomized clinical trial dealing with implantable defibrillators. This study enrolled post-transmural infarct patients having documented NSVT, left ventricular dysfunction (ejection fraction 35% or lower) and inducible and nonsuppressible NSVT. The study was recently terminated because of an emergence of a highly significant lower mortality with the ICD therapy than with conventional drug therapy. The future for patients at an increased risk of sudden cardiac death is much brighter with future refinement of the ICD system and antiarrhythmic drug therapy, and with further improvement in the therapy directed at the underlying structural heart disease.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Humans; Multicenter Studies as Topic; Myocardial Infarction; Randomized Controlled Trials as Topic

The incidence and prevalence of congestive heart failure increase exponentially with advancing age. Congestive heart failure in the elderly is characterized by a multifactorial etiology, a high proportion of accompanying degenerative changes of the cardiovascular system and age-specific problems regarding diagnosis and treatment. The treatment strategy is the same as in younger patients, but the higher incidence of adverse effects and complications demands special awareness. The majority of decompensations leading to hospitalization are precipitated by insufficient compliance in life style change and drug intake.

Topics: Adult; Aged; Aging; Arrhythmias, Cardiac; Arteriosclerosis; Cardiomyopathies; Cardiovascular Agents; Coronary Disease; Heart Failure; Humans; Hypertension; Incidence; Middle Aged; Prevalence

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Emergencies; Heart Failure; Hemodynamics; Humans; Shock, Cardiogenic

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

Myocardial infarction (MI), myocardial ischemia, ventricular dysrhythmias, and sudden cardiac death (SCD) occur most frequently in the morning, especially in the first few hours after awakening. Among individual patients, however, this pattern may vary widely. Peaks in heart rate, blood pressure, and platelet aggregability and a trough in fibrinolytic activity are thought to influence the morning onset of events. beta-Blockers may blunt the peak occurrence of MI, SCD, and ischemia. Some calcium channel blockers may modify the pattern of ischemia. Alternate-day therapy with 325 mg of aspirin has been shown to blunt the morning onset of MI. The efficacy of thrombolytics may be affected by daily fluctuations in fibrinolytic activity.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Circadian Rhythm; Death, Sudden, Cardiac; Heart Rate; Humans; Myocardial Infarction; Risk Factors

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

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

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

Treatment of patients with heart failure due to major ventricular systolic dysfunction should aim not only at symptomatic but also at prognostic improvement. If correction of the underlying problem is not possible, treatment should slow down the progression of cardiac failure and eliminate triggers for sudden cardiac death due to electromechanical dissociation or arrhythmias. In every patient with chronic congestive heart failure screening for myocardial ischemia and complete revascularization is mandatory, if possible. In patients with coronary artery disease and diminished systolic function, beta-blockade may improve prognosis by reducing ischemic events and sudden cardiac death. The incidence of life-threatening arrhythmias in patients with heart failure may be reduced by eliminating facilitating factors like electrolyte disturbances, altered autonomic tone and raised intracardiac pressure rather than by antiarrhythmic medical treatment itself. One of the most important prognostic aspects in treatment is the interference with the development of the cardiomyopathy of overload, uniformly observed in chronic congestive heart failure. Modification of mechanical and neuroendocrine stimuli may postpone myocardial hypertrophy and interstitial hyperplasia as a consequence of altered gene expression. Early treatment with ACE inhibitors and in certain patients with betablockers are the most promising strategies to delay the progression of the disease. In contrast, positive inotropic drugs, including digitalis and phosphodiesterase inhibitors, do not improve prognosis. Calcium antagonists should also be used with restriction, as Verapamil and Diltiazem, but also Nifedipine may adversely affect the outcome in congestive heart failure patients.

Topics: Arrhythmias, Cardiac; Cardiomyopathies; Cardiovascular Agents; Coronary Disease; Heart Failure; Humans; Myocardial Revascularization; Prognosis

The first part of this two-part article discussed the equipment needed for pediatric resuscitations and the techniques used for cardiopulmonary assessment, airway securance, circulatory maintenance and intravascular access. In this second part, additional life support measures are reviewed, including fluid therapy, resuscitation medications and the management of cardiac rhythm disturbances.

Topics: Arrhythmias, Cardiac; Bereavement; Cardiovascular Agents; Child; Child, Preschool; Diagnosis, Differential; Electrocardiography; Emergencies; Family; Fluid Therapy; Humans; Infant; Infant, Newborn; Life Support Care; Pediatrics; Respiration, Artificial; Resuscitation

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Death, Sudden; Digitalis; Diuretics; Heart Failure; Humans; Phosphodiesterase Inhibitors; Plants, Medicinal; Plants, Toxic; Vasodilator Agents

Patients with prostheses of the cardiac valve are, related to the total population, only a small part. But their number permanently increases. Alone in our clinic since 1973 3,250 patients have been provided with artificial cardiac valves. Thus more and more physicians are confronted with the problems of these patients. The long-term results after replacement of the cardiac valves are very essentially influenced by the prevention and well-timed recognition of complications, respectively. For this reason the medicamentous therapy is demonstrated on the basis of own experiences and modern literature. It is clearly pointed out that after replacement of the cardiac valve a permanent cardiologic control is necessary. In detail is reported on the therapy of cardiac insufficiency including disturbances of the cardiac rhythm, on the prophylaxis of thromboembolism as well as on the prophylaxis of endocarditis.

Topics: Anti-Bacterial Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Endocarditis; Heart Failure; Heart Valve Prosthesis; Humans; Postoperative Complications

Like all other scientific disciplines, preclinical pharmacological research is subject to permanent changes. New measuring devices and the possibility of continuous on line data acquisition have markedly influenced basic research in this field. Another aim of modern cardiovascular pharmacology is the testing of promising drugs in clinically relevant animal models of disease, particularly under conditions, referring to the everyday situation in patients, e.g. physical activity. Investigations carried out in this way allow an exact assessment of the clinical efficacy of new drugs, and are, thus, clearly indispensable, also from the ethical point of view, before primary evaluation of the drug in man.

Topics: Angina Pectoris; Animals; Arrhythmias, Cardiac; Austria; Cardiovascular Agents; Cats; Dogs; Drug Evaluation, Preclinical; Electric Countershock; Humans; Hypertension; Myocardial Infarction; Pharmacology; Rats; Research

There are many reasons to expect magnesium deficiency in patients with chronic congestive heart failure. Medical therapy, neurohormonal activation and decreased dietary intake could all contribute to low concentrations of serum and muscle magnesium. Although the ideal serum level of this electrolyte is not known, multiple studies have documented lower magnesium concentrations in patients with heart failure than in normal persons. Magnesium deficiency could theoretically produce hemodynamic deterioration and ventricular arrhythmias. These complications have been observed in animals and in patients without heart failure, and magnesium repletion has reversed the adverse effects of hypomagnesemia in some patients. However, the consequences of chronic depletion of the electrolyte have not been adequately evaluated. Because of the high incidence of sudden death in patients with severe congestive heart failure, well designed investigations to determine the importance of magnesium are needed.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Heart Ventricles; Hemodynamics; Humans; Magnesium; Magnesium Deficiency

Beta blockers, glucose-insulin-potassium, nitrates, and thrombolytic interventions have been demonstrated to reduce the mortality of acute MI. Because of the number of interventions available, it will become progressively more difficult to isolate their additional benefits. The next challenge will be to determine the ideal combination of interventions to limit infarct size maximally in the context of early reperfusion, thereby limiting reperfusion injury and further improving salvage.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Coronary Care Units; Humans; Monitoring, Physiologic; Myocardial Infarction

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

Atherosclerotic coronary artery disease is an important problem in the elderly and is the leading cause of death. It is a diagnosis that is often difficult to make; signs and symptoms of angina pectoris and myocardial infarction can be atypical in the elderly patient for a variety of reasons. The chest radiograph, electrocardiogram, and echocardiogram can provide diagnostic clues as to the presence of coronary artery disease. Exercise testing is foremost among the noninvasive diagnostic modalities, but it has significant limitations particular to the elderly patient. These include a decreased ability to exercise in the elderly, difficulty in interpretation because of an abnormal resting electrocardiogram, and the nature of an imperfect test that provides a statement of probability rather than an unequivocal diagnosis. Cardiac catheterization can be performed with minimal risk in selected, particularly unstable patients, in whom a surgical alternative is contemplated. The elderly patient can benefit as much from coronary artery bypass graft surgery as younger counterparts, albeit with a modestly increased risk. The medical therapy of coronary artery disease, stable and unstable angina, and myocardial infarction is not substantially different in the older patient. Nitrates, beta blockers, and calcium antagonists provide relief of anginal symptoms. The older patient stands to derive the same benefits from CCU monitoring as does the younger patient. An increased awareness of adverse drug reactions is necessary, however, and as for patients of any age, the particular goals of therapy may differ substantially and require an individualized approach.

Topics: Aged; Angina, Unstable; Arrhythmias, Cardiac; Cardiac Catheterization; Cardiovascular Agents; Coronary Artery Bypass; Coronary Disease; Echocardiography; Exercise Test; Humans; Myocardial Infarction

Topics: Adrenergic alpha-Agonists; Adrenergic beta-Antagonists; Angina Pectoris; Arrhythmias, Cardiac; Calcium Channel Blockers; Cardiovascular Agents; Digitalis; Diuretics; Hemodynamics; Humans; Hypertension; Isometric Contraction; Nitroglycerin; Physical Exertion; Plants, Medicinal; Plants, Toxic

Knowledge of the dosage, rate and route of administration, and potential side effects of drugs used to treat cardiac disease in horses has been refined. The judicious use of these drugs can increase exercise capacity, improve health, and potentially prolong life. Currently, antiarrhythmics (quinidine, lidocaine), positive inotropies (digoxin), and diuretics (furosemide) are the primary agents used to treat cardiovascular disease in horses. The development of newer drugs (verapamil, milrinone, bumetanide) and their usefulness in therapy for horses with cardiovascular disease require further investigation.

Topics: Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Cardiovascular Diseases; Edema; Female; Heart Rate; Horse Diseases; Horses; Male; Myocardial Contraction

An appreciation of the hemodynamic and biochemical changes induced by drugs is critical for a logical diagnostic interpretation of graded stress tests and the evaluation of the projected exercise prescription and exercise programs that a patient is asked to follow. Drug therapy is clearly not a contraindication to acute or chronic exercise as long as the potential benefits and complications of exercise and drug interaction are considered.

Topics: Angina Pectoris; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Coronary Disease; Heart Failure; Humans; Hypertension; Physical Exertion

Topics: Acute Disease; Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Coronary Disease; Coronary Vessels; Diastole; Dinoprostone; Dogs; Heart Arrest, Induced; Humans; Infusions, Parenteral; Myocardial Infarction; Perfusion; Prostaglandins E; Streptokinase; Time Factors

The general principles that apply to treatment of arrhythmias in the critically ill include, first, an immediate correction of arrhythmias that result in hemodynamic deterioration. This more frequently necessitates DC cardioversion, pacing, or intravenous therapy than is seen in an otherwise healthy patient. Second, having resuscitated the patient and treated the arrhythmia, the physician should be acutely aware of any precipitating factors, which should then be corrected in order to prevent recurrence of the arrhythmia. Third, the physician should also be aware of the potential proarrhythmic effects of his or her antiarrhythmic drug therapy and be prepared to withdraw therapy when it appears that the arrhythmia has worsened following drug treatment. In the future, new technologic developments, including improved defibrillation systems, intracardiac catheters for defibrillation, and automatic arrhythmia detectors using intravascular catheters, may aid in the diagnosis and treatment of recurrent arrhythmias in the critically ill.

Topics: Arrhythmias, Cardiac; Cardiac Pacing, Artificial; Cardiovascular Agents; Critical Care; Electric Countershock; Heart Atria; Heart Ventricles; Humans

The common rhythm disturbances related to electrolyte imbalance are due predominantly to abnormalities of potassium. An understanding of the mechanism underlying these abnormalities is facilitated by a brief review of normal electrical activity during impulse propagation in cardiac tissue. Also discussed are the actions of all cardioactive and antiarrhythmic drugs on membrane permeability to ions. Lastly, the nonspecific arrhythmias associated with endocrine disturbances are outlined.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Cimetidine; Digitalis Glycosides; Electrocardiography; Endocrine System Diseases; Humans; Hypercalcemia; Hyperkalemia; Hypocalcemia; Hypokalemia; Magnesium; Psychotropic Drugs; Water-Electrolyte Balance; Water-Electrolyte Imbalance

At least 10% of the American population medically use prescribed psychopharmacological medications; and such psychotropic medications account for approximately 20% of all prescriptions in this country. Furthermore, there is widespread illicit use of psychoactive drugs, including narcotics, psychostimulants, and central nervous system depressants. All of these agents have potent effects on the cardiovascular system and, in addition, may undergo numerous drug-drug interactions with cardiovascular medications. Givaen the high incidence of both cardiovascular disease and psychoactive drug use in the United States, it is likely that clinicians manage many patients with cardiovascular disease, possibly receiving cardiovascular medications, and also needing psychopharmacological interventions. Consequently, the authors have reviewed the pharmacology of the major classes of psychoactive agents: (I & II) Antidepressants (tricyclic antidepressants and monoamine oxidase inhibitors); (III) Lithium Carbonate; (IV) Major Tranquilizers (phenothiazines, thioxanthenes, butryophenones, reserpine); and (V) Minor Tranquilizers, Sedatives, and Hypnotics (benzodiazepines and barbiturates) with respect to their cardiotoxicity, cardiovascular side effects, and drug-drug interactions. Management of the cardiovascular complications of psychotropic overdose is discussed, as well as potential therapeutic uses of psychopharmacological medications in patients with cardiovascular pathology.

Topics: Adrenergic alpha-Antagonists; Anti-Anxiety Agents; Antipsychotic Agents; Arrhythmias, Cardiac; Autonomic Nervous System; Basal Ganglia Diseases; Benzodiazepines; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular System; Chlorpromazine; Coronary Circulation; Drug Interactions; Electroencephalography; Humans; Neuromuscular Blocking Agents; Reserpine; Tranquilizing Agents

Topics: Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Coronary Circulation; Coronary Disease; Death, Sudden; Denervation; Dogs; Heart; Humans; Stellate Ganglion; Sympathectomy; Sympathetic Nervous System; Ventricular Fibrillation

Clinical trials and studies with ivabradine implicate cardiac pacemaker channels (HCN4) in the pathogenesis of atrial arrhythmias. Because acute changes in cardiac autonomic tone predispose to atrial arrhythmias, we studied humans in whom profound cardiac sympathetic activation was rapidly relieved to test influences of HCN4 inhibition with ivabradine on atrial arrhythmias. We tested 19 healthy participants with ivabradine, metoprolol, or placebo in a double blind, randomized, cross-over fashion on top of selective norepinephrine reuptake inhibition with reboxetine. Subjects underwent combined head up tilt plus lower body negative pressure testing followed by rapid return to the supine position. In the current secondary analysis with predefined endpoints before data unblinding, continuous finger blood pressure and ECG recordings were analyzed by two experienced cardiac electrophysiologists and a physician, blinded for treatment assignment. The total atrial premature activity (referred to as atrial events) at baseline did not differ between treatments. After backwards tilting, atrial events were significantly higher with ivabradine compared with metoprolol or with placebo. Unlike beta-adrenoreceptor blockade, HCN4 inhibition while lowering heart rate does not protect from atrial arrhythmias under conditions of experimental cardiac sympathetic activation. The model in addition to providing insight in the role of HCN4 in human atrial arrhythmogenesis may have utility in gauging potential atrial pro-arrhythmic drug properties.

Topics: Adolescent; Adult; Arrhythmias, Cardiac; Autonomic Nervous System; Blood Pressure; Cardiovascular Agents; Cross-Over Studies; Double-Blind Method; Heart Rate; Humans; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Ivabradine; Male; Muscle Proteins; Pacemaker, Artificial; Potassium Channels; Prospective Studies; Young Adult

In acute coronary syndrome (ACS), potassium levels <3.5 mEq/L are associated with ventricular arrhythmias. Current guidelines therefore recommend a potassium target >4.0 mEq/L in ACS. Our study evaluated the association between potassium levels, cardiac arrhythmias, and cardiovascular death in patients with non-ST-segment elevation myocardial infarction or unstable angina.. Potassium levels were measured in 6515 patients prior to randomization to receive either ranolazine or a placebo in the MERLIN-TIMI 36 trial. A seven-day continuous electrocardiographic assessment was obtained to determine the incidence of non-sustained ventricular tachycardia (NSVT) and ventricular pauses. The association between potassium levels and cardiovascular death was evaluated using a Cox proportional hazards regression model with multivariable adjustment.. The lowest risk of cardiovascular death was observed in patients with admission potassium levels between 3.5 and 4.5 mEq/L. Both lower and higher levels of potassium were associated with tachyarrhythmias and bradyarrhythmias, suggesting a potential mechanistic explanation for the increased risk of cardiovascular death at the extremes of potassium homeostasis.

Topics: Aged; Angina, Unstable; Arrhythmias, Cardiac; Cardiovascular Agents; Electrocardiography; Female; Humans; Male; Middle Aged; Non-ST Elevated Myocardial Infarction; Potassium; Ranolazine

The aim of this study was to investigate the effect of different treatment interventions on plasma N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) levels and early exercise tolerance in patients with acute ST-segment elevation myocardial infarction.. 146 consecutive patients with ST-segment elevation myocardial infarction who received emergency percutaneous coronary intervention (PCI) (n = 55), elective PCI (n = 47), or drug treatment (n = 44) were included. Plasma NT-proBNP levels and left ventricular ejection fractions (LVEFs) were measured before the treatment intervention and at 1 week and 1 month afterward. An exercise stress test was performed 1 month after the intervention, and the occurrences of major adverse cardiac events (MACE) were recorded at the 1-month follow-up.. Compared with the elective PCI and drug treatment groups, at 1 week and 1 month after the intervention, the emergency PCI group's plasma NT-proBNP levels were significantly lower, and the group's LVEFs were significantly higher (all P < 0.05). There was a significantly negative correlation between plasma NT-proBNP levels and LVEFs in each group (all P < 0.05). The positive exercise stress testing rates were 13.0%, 32.6%, and 38.6% in the emergency PCI, elective PCI, and drug treatment groups, respectively (P < 0.05). The occurrences of MACE in the emergency PCI, elective PCI, and drug treatment groups were 34.5%, 59.5%, and 65.9%, respectively (P < 0.05).. Emergency PCI resulted in lower plasma NT-proBNP levels, lower MACE incidence, higher LVEFs, and better early exercise tolerance compared with elective PCI or drug treatment, indicating that lower plasma NT-proBNP levels predicted a better prognosis.

Topics: Adult; Aged; Angioplasty; Arrhythmias, Cardiac; Biomarkers; Cardiovascular Agents; Exercise Test; Exercise Tolerance; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Treatment Outcome

Exposure to single pollutants e.g. particulate matter (PM) is associated with adverse health effects, but it does not represent a real world scenario that usually involves multiple pollutants.. Determine if simultaneous exposure to PM and NO₂ results in synergistic interactions.. Healthy young volunteers were exposed to clean air, nitrogen dioxide (NO₂, 0.5 ppm), concentrated fine particles from Chapel Hill air (PM(2.5)CAPs, 89.5 ± 10.7 µg/m³), or NO₂+PM(2.5)CAPs for 2 h. Each subject performed intermittent exercise during the exposure. Parameters of heart rate variability (HRV), changes in repolarization, peripheral blood endpoints and lung function were measured before and 1 and 18 h after exposure. Bronchoalveolar lavage (BAL) was performed 18 h after exposure.. NO₂ exposure alone increased cholesterol and HDL 18 h after exposure, decreased high frequency component of HRV one and 18 h after exposure, decreased QT variability index 1 h after exposure, and increased LDH in BAL fluid. The only significant change with PM(2.5)CAPs was an increase in HDL 1 h after exposure, likely due to the low concentrations of PM(2.5)CAPs in the exposure chamber. Exposure to both NO₂ and PM(2.5)CAPs increased BAL α1-antitrypsin, mean t wave amplitude, the low frequency components of HRV and the LF/HF ratio. These changes were not observed following exposure to NO₂ or PM(2.5)CAPs alone, suggesting possible interactions between the two pollutants.. NO₂ exposure may produce and enhance acute cardiovascular effects of PM(2.5)CAPs. Assessment of health effects by ambient PM should consider its interactions with gaseous copollutants.

Topics: Adult; Air Pollutants; alpha 1-Antitrypsin; Arrhythmias, Cardiac; Atmosphere Exposure Chambers; Bronchoalveolar Lavage Fluid; Cardiovascular Agents; Cardiovascular System; Cholesterol; Drug Synergism; Female; Heart Rate; Humans; Hypercholesterolemia; Lactate Dehydrogenases; Male; Nitrogen Dioxide; North Carolina; Particulate Matter; Young Adult

Depression is independently associated with poor outcomes among patients with acute cardiac disease. Collaborative care depression management programs have been used in outpatients to improve depression outcomes, but such a program had never been initiated in the hospital or used for patients with a wide range of cardiac illnesses.. This was a prospective, randomized trial of a low-intensity, 12-week collaborative care program versus usual care for 175 depressed patients hospitalized for acute coronary syndrome, arrhythmia, or heart failure. Study outcomes, assessed using mixed regression models to compare groups at 6 weeks, 12 weeks, and 6 months, included mental health (depression, cognitive symptoms of depression, anxiety, and mental health-related quality of life) and medical (physical health-related quality of life, adherence to medical recommendations, and cardiac symptoms) outcomes. Collaborative care subjects (n=90) had significantly greater improvements on all mental health outcomes at 6 and 12 weeks, including rates of depression response (collaborative care, 59.7% versus usual care 33.7%; odds ratio, 2.91; P=0.003 at 6 weeks; 51.5% versus 34.4%; odds ratio, 2.02; P=0.04 at 12 weeks), though these effects decreased after intervention. At 6 months, intervention subjects had significantly greater self-reported adherence and significantly reduced number and intensity of cardiac symptoms.. Among patients with a broad range of cardiac diagnoses, a collaborative care depression management program initiated during hospitalization led to significant improvements in multiple clinically important mental health outcomes and had promising effects on relevant medical outcomes after intervention. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00847132.

Topics: Acute Coronary Syndrome; Aged; Antidepressive Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Depression; Female; Heart Failure; Humans; Inpatients; Male; Middle Aged; Patient Compliance; Prospective Studies; Quality of Life; Regression Analysis; Single-Blind Method; Treatment Outcome

Ivabradine is the first specific heart rate-lowering agent that has completed clinical development for stable angina pectoris. The aim of the present study was to investigate the effects of ivabradine therapy on P-wave duration, dispersion and QT duration, dispersion in coronary artery disease patients.. The study population consisted of 21 patients with CAD who have confirmed by coronary angiography previously. Written informed consent was obtained in all patients. Twelve-lead electrocardiogram was recorded for each subject at a rate of 50mm/s on admission and repeated after 1 month ivabradine therapy. QT duration, QT dispertion, maximum and minimum QT duration calculated. Maximum and minimum P wave and P wave dispersion has been calculated. Heart rate was decreased after ivabradine therapy. (75+/-15 and 63+/-10, P=0.02).There was no difference between Pmax, Pmin and Pdis values before and after treatment. QTmax value was prolonged after treatment. (410+/-43 and 431+/-14, P=0,005) but there was no difference between cQTmax value.(455+/-38 and 439+/-21) There was no difference between QTdis and cQTdis values before and after treatment. (44+/-18 & 49+/-14; and 49+/-22 & 48+/-15). QTmax was prolonged after ivabradine therapy but cQTmax, Pdis, QTdis and cQTdis were not prolonged.. There is no relationship between ivabradine therapy and increased risk of ventricular and atrial arrhythmia in coronary artery disease patient.

Topics: Adult; Aged; Arrhythmias, Cardiac; Benzazepines; Cardiovascular Agents; Coronary Angiography; Coronary Artery Disease; Female; Heart Rate; Humans; Ivabradine; Male; Middle Aged

Implantable cardioverter-defibrillators and cardiac resynchronization therapy defibrillators have relied on multiple ventricular fibrillation (VF) induction/defibrillation tests at implantation to ensure that the device can reliably sense, detect, and convert VF. The ASSURE Study (Arrhythmia Single Shock Defibrillation Threshold Testing Versus Upper Limit of Vulnerability: Risk Reduction Evaluation With Implantable Cardioverter-Defibrillator Implantations) is the first large, multicenter, prospective trial comparing vulnerability safety margin testing versus defibrillation safety margin testing with a single VF induction/defibrillation.. A total of 426 patients receiving an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator underwent vulnerability safety margin or defibrillation safety margin screening at 14 J in a randomized order. After this, patients underwent confirmatory testing, which required 2 VF conversions without failure at < or = 21 J. Patients who passed their first 14-J and confirmatory tests, irrespective of the results of their second 14-J test, had their devices programmed to a 21-J shock for ventricular tachycardia (VT) or VF > or = 200 bpm and were followed up for 1 year. Of 420 patients who underwent 14-J vulnerability safety margin screening, 322 (76.7%) passed. Of these, 317 (98.4%) also passed 21-J confirmatory tests. Of 416 patients who underwent 14-J defibrillation safety margin screening, 343 (82.5%) passed, and 338 (98.5%) also passed 21-J confirmatory tests. Most clinical VT/VF episodes (32 of 37, or 86%) were terminated by the first shock, with no difference in first shock success. In all observed cases in which the first shock was unsuccessful, subsequent shocks terminated VT/VF without complication.. Although spontaneous episodes of fast VT/VF were limited, there was no difference in the odds of first shock efficacy between groups. Screening with vulnerability safety margin or defibrillation safety margin may allow for inductionless or limited shock testing in most patients.

Topics: Aged; Aged, 80 and over; Arrhythmias, Cardiac; Cardiovascular Agents; Combined Modality Therapy; Cross-Over Studies; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Stimulation; Equipment Design; Female; Follow-Up Studies; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Research Design; Risk Reduction Behavior; Single-Blind Method; Unnecessary Procedures; Ventricular Fibrillation

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

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

Aim of the present study was to assess the effect of epirubicin-based chemotherapy on QT interval dispersion in patients with aggressive non-Hodgkin lymphoma (NHL), and the effect of dexrazoxane supplementation. Prolongation of QT dispersion may not only represent a sensitive tool in identifying the first sign of anthracycline-induced cardiotoxicity, but it may serve also in identifying patients who are at risk of arrhythmic events.. Twenty untreated patients,

Topics: Antibiotics, Antineoplastic; Arrhythmias, Cardiac; Cardiovascular Agents; Drug Therapy, Combination; Electrocardiography; Epirubicin; Female; Heart Conduction System; Humans; Lymphoma, Non-Hodgkin; Male; Razoxane; Time Factors

Atrial fibrillation (AF) is a very common cardiac arrhythmia with an increased mortality in patients with heart failure. Whether the best therapeutic approach to these patients is to restore sinus rhythm or to adequately control the ventricular rate is still controversial. The aim of this study was to compare both strategies in patients with AF and nonischemic heart failure. One hundred and fifty-four patients with AF duration greater than 48 hours and nonischemic left ventricular dysfunction were randomized either to a rhythm (n = 84) or rate (n = 74) control group. The composite end points of the study were embolism, death, and exercise capacity. The average age of the patients was 61 +/- 10 years in the rhythm control group and 58 +/- 12 years in the rate control group (P = NS). The average follow-up period was 35 +/- 21 months in the rhythm control group and 37 +/- 19 months in the rate control group (P = NS). In the first year of the study, exercise capacity and left ventricular ejection fraction (LVEF) were improved in the rhythm control group compared to the exercise capacity and LVEF of the rate control group (P < 0.0001 and P = 0.0005, respectively). There were no statistically significant differences in the embolic event rate between the two groups (P = NS). The mortality rate, especially for death due to pump failure, was significantly higher in the rate control group at the end of the study (P < 0.0001). Restoring and maintaining sinus rhythm had a beneficial effect on mortality and exercise capacity in patients with nonischemic heart failure and AF.

Topics: Aged; Arrhythmias, Cardiac; Atrial Fibrillation; Cardiovascular Agents; Electric Countershock; Electrocardiography; Exercise Test; Exercise Tolerance; Female; Heart Failure; Heart Rate; Humans; Male; Middle Aged; Survival Analysis

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

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

Doxorubicin is one of the most effective anticancer drug, but its usefulness is limited by the risk of developing cardiomyopathy, cardiac dysfunction and ventricular arrhythmias. Dexrazoxane is used to protect against doxorubicin cardiotoxicity. It is uncertain whether the dexrazoxane-mediated cardioprotective effect will be reflected in electrophysiological properties of the heart. The aim of the present study was to evaluate the occurrence of frequency-domain signal-averaged electrocardiographic (SAECG) abnormalities of the QRS complex and the initial ST segment in patients treated with and without dexrazoxane. Thirty children and young adults 2 months - 15 years after completion of doxorubicin-containing therapy for Hodgkin's disease were evaluated with SAECG. Patients from group I (n = 13) received combined therapy with doxorubicin and dexrazoxane (DOX/DZX), patients from group II (n = 17) received doxorubicin without dexrazoxane (DOX). Using fast Fourier transformation within the QRS complex and the initial ST segment, area ratio (AR) values 40-100/0-40 Hz were calculated. Significant differences in these frequency parameters in the QRS complex between DOX/DZX group and DOX group (19.45+/-12.72 vs 46.18+/-43.06; p = 0.03) might indicate protective effect of dexrazoxane on electrophysiological myocardial properties.

Topics: Adolescent; Antineoplastic Agents; Arrhythmias, Cardiac; Cardiomyopathies; Cardiovascular Agents; Child; Child, Preschool; Combined Modality Therapy; Doxorubicin; Electrocardiography; Female; Fourier Analysis; Hodgkin Disease; Humans; Infant; Male; Razoxane

The arrhythmogenic hazard of adenosine treatment in an emergency room (ER) has not been established. Thus, in this study, we set out to prospectively determine the prevalence and clinical consequences of the arrhythmogenic effects associated with urgent adenosine treatment in the ER. One hundred and sixty consecutive patients treated with adenosine for regular wide or narrow complex tachyarrhythmias at our ER were included in the study. An initial bolus of 3 mg of adenosine was used, up to a maximum dose of 18 mg (mode 6 mg). Proarrhythmia was defined as the new appearance of any brady- or tachyarrhythmia within 1 minute from the bolus administration of adenosine. Of the 160 study patients, 84% had narrow complex tachycardia and 16% had wide complex tachycardia. Adenosine was effective in the diagnosis and/or treatment of the underlying arrhythmia in 92%. The overall prevalence of adenosine-induced proarrhythmia was 13%, including prolonged AV block inducing asystole > 4 seconds (7%), paroxysmal atrial fibrillation (1%) and non-sustained ventricular tachycardia (5%). All adenosine-induced arrhythmias were transient and subsided spontaneously. It is concluded, firstly, that adenosine-induced proarrhythmia proved to be frequent in a consecutive ER series, and included potentially dangerous arrhythmias. Secondly, nevertheless, all adenosine-induced arrhythmias subsided spontaneously and did not require treatment. Therefore, urgent adenosine treatment is safe and can be recommended in an emergency setting, provided a strict protocol of administration under close monitoring by highly trained personnel.

Topics: Adenosine; Adult; Age Distribution; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Comorbidity; Diabetes Mellitus; Drug Therapy, Combination; Drug Tolerance; Electrocardiography; Emergency Service, Hospital; Female; Humans; Hypertension; Hyperthyroidism; Italy; Logistic Models; Male; Middle Aged; Prevalence; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Sex Distribution; Tachycardia; Treatment Outcome

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

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

This study was conducted to explore mechanisms that could explain the possible clinical benefit of early administration of a beta 1-selective adrenoreceptor blocking agent or a bradycardiac drug as adjunct to thrombolysis in acute myocardial infarction.. The effects of beta-blockers given concomitantly with thrombolytic therapy in patients with acute myocardial infarction have not been fully examined. The potential role of specific bradycardiac agents lacking negative inotropism as an alternative to beta-blockers in this setting has never been studied in humans.. In a double-blind study, we examined the effects of early intravenous and continued oral administration of a beta-blocker (atenolol), a specific bradycardiac agent (alinidine) or placebo on left ventricular function, late coronary artery patency, infarct size, exercise capacity and incidence of arrhythmias.. A total of 292 patients with acute myocardial infarction of < or = 5 h duration and without contraindications to thrombolytic or beta-blocker therapy were studied. Of these, 100 were allocated to treatment with atenolol (5 to 10 mg intravenously followed by 25 to 50 mg orally every 12 h), 98 to alinidine (20 to 40 mg intravenously followed by 20 to 40 mg orally every 8 h) and 94 to placebo. All patients received 100 mg of alteplase over 3 h and full intravenous heparinization. No significant differences in coronary artery patency, global ejection fraction or regional wall motion were observed at 10 to 14 days among the three groups. Likewise, enzymatic and scintigraphic infarct size were also very similar. Neither atenolol nor alinidine was associated with a significant reduction in the incidence of arrhythmias during the 1st 24 h. No significant differences in clinical events were observed, with the exception of a greater incidence of nonfatal pulmonary edema in the atenolol group (6% vs. 1% in the alinidine group and 0% in the placebo group, p = 0.021).. In the absence of contraindications, the administration of a beta-blocker or a specific bradycardiac agent together with thrombolytic therapy was safe. In this limited number of patients, these agents did not appear to enhance myocardial salvage or preservation of left ventricular function or to reduce the incidence of major arrhythmias in the early phase of infarction.

Topics: Adult; Aged; Arrhythmias, Cardiac; Atenolol; Cardiovascular Agents; Clonidine; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Exercise Test; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Myocardial Infarction; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome; Vascular Patency; Ventricular Function, Left

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Humans

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Child; Heart Rate; Humans; Ivabradine

Adults with systemic right ventricle have a significant risk for long-term complications such as arrhythmias or heart failure.. A nationwide retrospective study based on the German National Register for Congenital Heart Disease was performed. Patients with transposition of the great arteries after atrial switch operation or congenitally corrected TGA were included.. Two hundred and eight-five patients with transposition of the great arteries after atrial switch operation and 95 patients with congenitally corrected transposition of the great arteries were included (mean age 33 years). Systolic function of the systemic ventricle was moderately or severely reduced in 25.5 % after atrial switch operation and in 35.1% in patients with congenitally corrected transposition. Regurgitation of the systemic atrioventricular valve was present in 39.5% and 43.2% of the cases, respectively. A significant percentage of patients also had a history for supraventricular or ventricular arrhythmias. However, polypharmacy of cardiovascular drugs was rare (4.5%) and 38.5 % of the patients did not take any cardiovascular medication. The amount of cardiovascular drugs taken was associated with NYHA class as well as systemic right ventricular dysfunction. Patients with congenitally corrected transposition were more likely to receive pharmacological treatment than patients after atrial switch operation.. A significant portion of patients with systemic right ventricle suffer from a relevant systemic ventricular dysfunction, systemic atrioventricular valve regurgitation, and arrhythmias. Despite this, medication for heart failure treatment is not universally used in this cohort. This emphasises the need for randomised trials in patient with systemic right ventricle.

Topics: Adult; Arrhythmias, Cardiac; Cardiovascular Agents; Congenitally Corrected Transposition of the Great Arteries; Heart Defects, Congenital; Heart Failure; Heart Ventricles; Humans; Retrospective Studies; Transposition of Great Vessels; Ventricular Function; Ventricular Function, Right

Between 2012 and 2017, the FDA approved 29 therapies for a cardiovascular disease (CVD) indication. Due to the limited literature on patient safety outcomes for recently approved CVD medications, this study investigated adverse drug reports (ADRs) reported in the FDA Adverse Event Reporting System (FAERS).. A disproportionality analysis of spontaneously reported ADR was conducted. Reports in FAERS from Quarter 1, 2012, through Quarter 1, 2019, were compiled, allowing a 2-year buffer following drug approval in 2017. Top 10 reported ADRs and reporting odds ratios (ROR; confidence interval (CI)), a measure of disproportionality, were analyzed and compared to drugs available prior to 2012 as appropriate.. Of 7,952,147 ADR reports, 95,016 (1.19%) consisted of reports for newly approved CVD medications. For oral anticoagulants, apixaban had significantly lower reports for anemia and renal failure compared to dabigatran and rivaroxaban but greater reports for neurological signs/symptoms, and arrhythmias. Evaluating heart failure drugs, sacubitril/valsartan had greater reports for acute kidney injury, coughing, potassium imbalances, and renal impairment but notably, lower for angioedema compared to lisinopril. Assessing familial hypercholesterolemia drugs, alirocumab had greater reports for joint-related-signs/symptoms compared to other agents in this category. A newer pulmonary arterial hypertension treatment, selexipag, had greater reports of reporting for bone/joint-related-signs/symptoms but riociguat had greater reports for hemorrhages and vascular hypotension.. Pharmacovigilance studies allow an essential opportunity to evaluate the safety profile of CVD medications in clinical practice. Additional research is needed to evaluate these reported safety concerns for recently approved CVD medications.

Topics: Adverse Drug Reaction Reporting Systems; Aminobutyrates; Arrhythmias, Cardiac; Biphenyl Compounds; Cardiovascular Agents; Cardiovascular Diseases; Databases, Factual; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacovigilance; United States; United States Food and Drug Administration

of the progress in arrhythmias in 2020. RACE4 and ALL-IN indicated that integrated nurse-led care improves outcomes in AF patients.3,4 The same was reported for early rhythm control therapy15 and cryoablation as initial AF treatment.25,26 Subcutaneous ICD was non-inferior to classical transvenous ICD therapy in PRAETORIAN.54 One mechanistic study showed that autoantibodies against misexpressed actin, keratin, and connexin-43 proteins create a blood-borne biomarker profile enhancing diagnosis of Brugada syndrome.50 Another mechanistic study indicated that transseptal LV pacing yields similar improvement in contractility as His bundle pacing whilst being more easy to execute.44 In PRE-DETERMINE a simple-to-use ECG risk score improved risk prediction in patients with ischemic heart disease possibly enhancing appropriate ICD therapy in high risk patients.58.

Topics: Arrhythmias, Cardiac; Brugada Syndrome; Cardiovascular Agents; Defibrillators, Implantable; Humans; Treatment Outcome

There has been great interest in phospholipids (PLs) from marine by-products due to their long-chain polyunsaturated fatty acids with unique health and functional properties. Here, marine PLs from squid viscera and gonads were comprehensively characterized and compared by UPLC-Q-Exactive Orbitrap/MS-based lipidomics analysis. A total of thirteen phospholipid classes including 1223 molecular species were identified and quantified in both resources. PC, PE and SM were further isolated from the total PLs of squid viscera and gonads, respectively. All isolated squid PL components were first evaluated for anti-inflammatory, antioxidant and cardiovascular effects using in vivo zebrafish models. Our results showed the diversity, content and physiological functions of PLs from squid by-products, which provided a basis for their future application in the nutritional and pharmaceutical industry.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Arrhythmias, Cardiac; Cardiovascular Agents; Chromatography, High Pressure Liquid; Decapodiformes; Fibrinolytic Agents; Gonads; Humans; Lipidomics; Mass Spectrometry; Phospholipids; Thrombosis; Viscera; Zebrafish

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Cardiovascular System; Humans; Out-of-Hospital Cardiac Arrest; Ventricular Fibrillation

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

Screening compounds for activity on the hERG channel using patch clamp is a crucial part of safety testing. Automated patch clamp (APC) is becoming widely accepted as an alternative to manual patch clamp in order to increase throughput whilst maintaining data quality. In order to standardize APC experiments, we have investigated the effects on IC. APC instruments SyncroPatch 384i, SyncroPatch 384PE and Patchliner, were used to record hERG expressed in HEK or CHO cells. Up to 27 CiPA compounds were used to investigate effects of voltage protocol, incubation time, labware and time between compound preparation and experiment on IC. All IC. Assessing the influence of different experimental conditions on hERG assay reliability, we conclude that either the step-ramp protocol recommended by CiPA or a standard 2-s step-pulse protocol can be used to record hERG; a minimum incubation time of 5 min should be used and although glass, Teflon, PP or polystyrene (PS) compound plates can be used for experiments, caution should be taken if using Teflon, PS or PP vessels as some adsorption can occur if experiments are not performed immediately after preparation. Our recommendations are not limited to the APC devices described in this report, but could also be extended to other APC devices.

Topics: Animals; Arrhythmias, Cardiac; Astemizole; Benchmarking; Calibration; Cardiovascular Agents; Cell Line; CHO Cells; Cricetulus; Drug Discovery; Drug Evaluation, Preclinical; ERG1 Potassium Channel; Heart; HEK293 Cells; Humans; Patch-Clamp Techniques; Phenethylamines; Polypropylenes; Polytetrafluoroethylene; Reference Standards; Reproducibility of Results; Sulfonamides; Terfenadine

Novel studies conducting cardiac safety assessment using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are promising but might be limited by their specificity and predictivity. It is often challenging to correctly classify ion channel blockers or to sufficiently predict the risk for Torsade de Pointes (TdP). In this study, we developed a method combining in vitro and in silico experiments to improve machine learning approaches in delivering fast and reliable prediction of drug-induced ion-channel blockade and proarrhythmic behaviour. The algorithm is based on the construction of a dictionary and a greedy optimization, leading to the definition of optimal classifiers. Finally, we present a numerical tool that can accurately predict compound-induced pro-arrhythmic risk and involvement of sodium, calcium and potassium channels, based on hiPSC-CM field potential data.

Topics: Algorithms; Arrhythmias, Cardiac; Cardiovascular Agents; Computational Biology; Databases, Factual; Drug Evaluation, Preclinical; Humans; Induced Pluripotent Stem Cells; Ion Channels; Models, Cardiovascular; Myocytes, Cardiac; Torsades de Pointes

Despite the progress in the management of patients with adult congenital heart disease (ACHD), a significant proportion of patients still develop pulmonary hypertension (PH). We aimed to highlight the rate of the complications in PH-ACHD and the predicting factors of cumulative mortality risk in this population.. Data were obtained from the cohort of the national registry of ACHD in Greece from February 2012 until January 2018.. Overall, 65 patients receiving PH-specific therapy were included (mean age 46.1±14.4 years, 64.6% females). Heavily symptomatic (New York Heart Association (NYHA) class III/IV) were 53.8% of patients. The majority received monotherapy, while combination therapy was administered in 41.5% of patients. Cardiac arrhythmia was reported in 30.8%, endocarditis in 1.5%, stroke in 4.6%, pulmonary arterial thrombosis in 6.2%, haemoptysis in 3.1% and hospitalisation due to heart failure (HF) in 23.1%. Over a median follow-up of 3 years (range 1-6), 12 (18.5%) patients died. On univariate Cox regression analysis history of HF hospitalisation emerged as a strong predictor of mortality (HR 8.91, 95% CI 2.64 to 30.02, p<0.001), which remained significant after adjustment for age and for NYHA functional class.. Long-term complications are common among patients with PH-ACHD. Hospitalisations for HF predict mortality and should be considered in the risk stratification of this population.

Topics: Adult; Arrhythmias, Cardiac; Cardiovascular Agents; Female; Follow-Up Studies; Greece; Heart Defects, Congenital; Heart Failure; Hospitalization; Humans; Hypertension, Pulmonary; Male; Middle Aged; Mortality; Prognosis; Registries; Risk Assessment; Stroke

Syncope accounts for 1% of emergency department (ED) visits, yet few experience a serious adverse event (SAE). Two-thirds of syncope patients are transported to the ED by ambulance, placing considerable burden on emergency medical services (EMS), and many of these transports may be unnecessary. We estimated the proportion of syncope patients who fell into a low-risk category based on an ED diagnosis of vasovagal syncope and the absence of EMS intervention, hospitalization, or SAE.. We conducted a multicentre prospective cohort study enrolling adult syncope patients transported to the ED by ambulance over 13 months. We collected demographics and EMS interventions, and followed patients for 30 days to identify all SAE, including death, dysrhythmia, myocardial infarction, aortic dissection, pulmonary embolism, subarachnoid hemorrhage, significant hemorrhage, and related procedural interventions.. Of 990 (67.2%) patients transported to the ED by ambulance, 121 had EMS interventions, 137 suffered 30-day SAE, 393 (39.7%; 95%CI 36.6, 42.8) were deemed low risk, 41 patients with vasovagal syncope were lost to follow-up, and 298 patients were diagnosed with non-vasovagal syncope. During transport, 121 (12.2%; 95%CI 10.2, 14.3) patients underwent some EMS intervention, and 137 (14.6%; 95%CI 12.4, 16.9) suffered SAEs within 30 days.. About 40% of patients transported to the ED by ambulance are at low risk and may not benefit from paramedic care or transport to a hospital. A robust clinical decision tool would help identify patients safe for treat-and-release, diversion to alternative care, or rapid offload into low-acuity ED areas, potentially reducing EMS workload and cost.. Les syncopes motivent 1 % des consultations au service des urgences (SU), mais le malaise entraîne peu d’événements indésirables graves (EIG). Ainsi, deux tiers des patients ayant subi une syncope sont transportés en ambulance au SU, ce qui impose un lourd fardeau sur les services médicaux d’urgence (SMU), et pourtant bon nombre de transports effectués seraient non nécessaires. Aussi l’étude visait-elle à estimer la proportion de patients ayant subi une syncope dont l’état serait jugé à faible risque d’après le diagnostic de syncope vasovagale posé au SU ainsi que d’après l’absence d’intervention faite par les SMU, d’hospitalisation ou d’EIG.. Il s’agit d’une étude prospective de cohortes, multicentrique, menée chez des adultes qui ont subi une syncope et qui ont été transportés en ambulance au SU, sur une période de 13 mois. Ont été recueillies des données démographiques ainsi que les notes sur les interventions effectuées par les SMU; à cela s’ajoute un suivi de 30 jours aux fins de collecte de renseignements sur tout EIG : mort, arythmie, infarctus du myocarde, dissection de l’aorte, embolie pulmonaire, hémorragie sous-arachnoïdienne, hémorragie importante et gestes interventionnels liés aux troubles en question.. Au total, 990 patients (67,2 %) ont été transportés en ambulance au SU; sur ce nombre, 121 ont subi des interventions pratiquées par les SMU; 137 ont connu un EIG au cours des 30 jours suivant le malaise; 393 (39,7 %; IC à 95 % : 36,6-42,8) ont été jugés à faible risque; 41 ayant fait une syncope vasovagale ont été perdus de vue durant le suivi; et 298, ont fait une syncope non vasovagale. Durant le transport, 121 patients (12,2 %; IC à 95 % : 10,2-14,3) ont subi une forme quelconque d’intervention par les SMU et, au cours des 30 jours de suivi, 137 (14,6 %; IC à 95 % : 12,4-16,9) ont connu un EIG.. Environ 40 % des patients transportés en ambulance au SU connaissent un faible risque et, dans leur cas, la prestation de soins paramédicaux ou le transport à l’hôpital pourraient ne pas être nécessaires. Un outil d’aide à la décision clinique qui soit digne de confiance pourrait faciliter le repérage des patients dont l’état se prêterait au traitement suivi du congé, à une orientation vers d’autres types de soins ou à un passage rapide dans des zones de petites urgences, ce qui permettrait à la fois de réduire la charge de travail des SMU ainsi que les coûts.

Topics: Ambulances; Antiemetics; Arrhythmias, Cardiac; Canada; Cardiac Pacing, Artificial; Cardiovascular Agents; Cohort Studies; Drug Utilization; Emergency Service, Hospital; Female; Glucose; Humans; Hypnotics and Sedatives; Male; Middle Aged; Sweetening Agents; Syncope

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

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

Short QT syndrome (SQTS) predisposes afflicted patients to sudden cardiac death. Until now, only one drug-quinidine-has been shown to be effective in patients with SQTS type 1(SQTS1). The objective of this study was to use human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with SQTS1 to search for potentially effective drugs for the treatment of SQTS1 patients. Patch clamp and single-cell contraction measurements were employed to assess drug effects. Ivabradine, mexiletine, and ajmaline but not flecainide, ranolazine, or amiodarone prolonged the action potential duration (APD) in hiPSC-CMs from an SQTS1 patient. Ivabradine, ajmaline, and mexiletine inhibited KCNH2 channel currents significantly, which may underlie their APD-prolonging effects. Under proarrhythmic epinephrine stimulation in spontaneously beating SQTS1 hiPSC-CMs, ivabradine, mexiletine, and ajmaline but not flecainide reduced the epinephrine-induced arrhythmic events. The results demonstrate that ivabradine, ajmaline, and mexiletine may be candidate drugs for preventing tachyarrhythmias in SQTS1 patients.

Topics: Action Potentials; Arrhythmias, Cardiac; Cardiovascular Agents; Dose-Response Relationship, Drug; Epinephrine; ERG1 Potassium Channel; Heart Conduction System; Heart Defects, Congenital; Humans; Induced Pluripotent Stem Cells; Myocytes, Cardiac

Cardiac tissue engineering provides unique opportunities for cardiovascular disease modeling, drug testing, and regenerative medicine applications. To recapitulate human heart tissue, we combined human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with a chitosan-enhanced extracellular-matrix (ECM) hydrogel, derived from decellularized pig hearts. Ultrastructural characterization of the ECM-derived engineered heart tissues (ECM-EHTs) revealed an anisotropic muscle structure, with embedded cardiomyocytes showing more mature properties than 2D-cultured hiPSC-CMs. Force measurements confirmed typical force-length relationships, sensitivity to extracellular calcium, and adequate ionotropic responses to contractility modulators. By combining genetically-encoded calcium and voltage indicators with laser-confocal microscopy and optical mapping, the electrophysiological and calcium-handling properties of the ECM-EHTs could be studied at the cellular and tissue resolutions. This allowed to detect drug-induced changes in contraction rate (isoproterenol, carbamylcholine), optical signal morphology (E-4031, ATX2, isoproterenol, ouabin and quinidine), cellular arrhythmogenicity (E-4031 and ouabin) and alterations in tissue conduction properties (lidocaine, carbenoxolone and quinidine). Similar assays in ECM-EHTs derived from patient-specific hiPSC-CMs recapitulated the abnormal phenotype of the long QT syndrome and catecholaminergic polymorphic ventricular tachycardia. Finally, programmed electrical stimulation and drug-induced pro-arrhythmia led to the development of reentrant arrhythmias in the ECM-EHTs. In conclusion, a novel ECM-EHT model was established, which can be subjected to high-resolution long-term serial functional phenotyping, with important implications for cardiac disease modeling, drug testing and precision medicine. STATEMENT OF SIGNIFICANCE: One of the main objectives of cardiac tissue engineering is to create an in-vitro muscle tissue surrogate of human heart tissue. To this end, we combined a chitosan-enforced cardiac-specific ECM hydrogel derived from decellularized pig hearts with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from healthy-controls and patients with inherited cardiac disorders. We then utilized genetically-encoded calcium and voltage fluorescent indicators coupled with unique optical imaging techniques and force-measurements to study the functional properties of the generated engineered

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Calcium; Cardiovascular Agents; Disease Models, Animal; Drug Evaluation, Preclinical; Extracellular Matrix; Heart; Humans; Hydrogels; Induced Pluripotent Stem Cells; Models, Cardiovascular; Myocardial Contraction; Myocytes, Cardiac; Organ Specificity; Swine; Tissue Engineering

The management of pregnancy in patients with mitral valve stenosis disease continues to pose a challenge to the clinician.. The aim of study was to evaluate the association between mitral valve stenosis and maternal and fetal out come.. Eighty-three pregnant women with mitral valve disease, followed-up from 2009 to 2012, were prospectively evaluated medical history, NYHA class assessment, ECG and echocardiography were performed during pregnancy and after delivery.. Women with mitral stenosis had significantly clinical higher incidence of complications deterioration of clinical status was observed (44.57%, P=0.0001) congestive heart failure had observed (27.71%, P=0.0001), hospitalization (33.73%, P=0.0001), need of cardiac medications (53.75%, P=0.009), arrhythmias (16%, P<0.05), New born outcome, mitral stenosis had an effect on fetal outcome. We had increasing preterm, delivery (17.50%, P=0.018), hypotrophy (20.48%, P=0.001), intra-uterine growth retardation (12.04%, P=0.011) new born hospitalizations (13.25%, P=0.03) Increased maternal morbidity and unfavorable fetal outcome was seen mostly in patients with moderate and severe mitral stenosis.. Pregnant with critical mitral stenosis form a high-risk groups of life-threatening complications. There is need for close maternal follow-up and fetal surveillance and repair of mitral stenosis should be performed before pregnancy.

Topics: Adult; Algeria; Arrhythmias, Cardiac; Cardiovascular Agents; Drug Utilization; Female; Fetal Growth Retardation; Heart Failure; Hospitalization; Hospitals, University; Humans; Infant, Newborn; Middle Aged; Mitral Valve Stenosis; Pregnancy; Pregnancy Complications, Cardiovascular; Premature Birth; Prospective Studies; Young Adult

Hospitalized patients have a high prevalence of prolonged QTc and are a high-risk population for Torsades de Pointes (TdP). One modifiable risk factor for TdP is the use of QT prolonging drugs. Electronically alerting providers who are ordering QT prolonging drugs in at-risk patients may help to achieve safer prescribing practices. Our previous study decreased inappropriate prescription of IV haloperidol by 36% using a targeted "smart" electronic alert. We wanted to assess an approach to expanding this type of electronic alert to commonly used QT prolonging medications and evaluate how this would affect prescribing practice. This retrospective cohort study evaluated the impact of these alerts for 12 frequently prescribed high-risk medications across a major health system. Between October 2016 and June 2017, a total of 6453 alerts fired and resulted in 3020 (46.8%) orders being cancelled by the provider. Our focused electronic alert significantly decreased prescribing of QT prolonging medications in high-risk patients.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Electrocardiography; Heart Rate; Humans; Retrospective Studies; Risk Factors; Torsades de Pointes

Spontaneous calcium (Ca) waves in cardiac myocytes underlie delayed afterdepolarizations (DADs) that trigger cardiac arrhythmias. How these subcellular/cellular events overcome source-sink factors in cardiac tissue to generate DADs of sufficient amplitude to trigger action potentials is not fully understood. Here, we evaluate quantitatively how factors at the subcellular scale (number of Ca wave initiation sites), cellular scale (sarcoplasmic reticulum (SR) Ca load), and tissue scale (synchrony of Ca release in populations of myocytes) determine DAD features in cardiac tissue using a combined experimental and computational modeling approach. Isolated patch-clamped rabbit ventricular myocytes loaded with Fluo-4 to image intracellular Ca were rapidly paced during exposure to elevated extracellular Ca (2.7 mmol/L) and isoproterenol (0.25 μmol/L) to induce diastolic Ca waves and subthreshold DADs. As the number of paced beats increased from 1 to 5, SR Ca content (assessed with caffeine pulses) increased, the number of Ca wave initiation sites increased, integrated Ca transients and DADs became larger and shorter in duration, and the latency period to the onset of Ca waves shortened with reduced variance. In silico analysis using a computer model of ventricular tissue incorporating these experimental measurements revealed that whereas all of these factors promoted larger DADs with higher probability of generating triggered activity, the latency period variance and SR Ca load had the greatest influences. Therefore, incorporating quantitative experimental data into tissue level simulations reveals that increased intracellular Ca promotes DAD-mediated triggered activity in tissue predominantly by increasing both the synchrony (decreasing latency variance) of Ca waves in nearby myocytes and SR Ca load, whereas the number of Ca wave initiation sites per myocyte is less important.

Topics: Aniline Compounds; Animals; Arrhythmias, Cardiac; Caffeine; Calcium; Calcium Signaling; Cardiovascular Agents; Computer Simulation; Fluorescent Dyes; Intracellular Space; Male; Membrane Potentials; Models, Cardiovascular; Myocytes, Cardiac; Patch-Clamp Techniques; Rabbits; Sarcoplasmic Reticulum; Voltage-Sensitive Dye Imaging; Xanthenes

Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are emerging as new and human-relevant source in vitro model for cardiac safety assessment that allow us to investigate a set of 20 reference drugs for predicting cardiac arrhythmogenic liability using optical action potential (oAP) assay.. Here, we describe our examination of the oAP measurement using a voltage sensitive dye (Di-4-ANEPPS) to predict adverse compound effects using hiPS-CMs and 20 cardioactive reference compounds. Fluorescence signals were digitized at 10kHz and the records subsequently analyzed off-line. Cells were exposed to 30min incubation to vehicle or compound (n=5/dose, 4 doses/compound) that were blinded to the investigating laboratory. Action potential parameters were measured, including rise time (T. Significant effects on oAPD were sensitively detected with 11 QT-prolonging drugs, while oAPD shortening was observed with I. The results of this blinded study indicate that OAP is a sensitive method to accurately detect drug-induced effects (i.e., duration/QT-prolongation, shortening, beat rate, and incidence of early after depolarizations) in hiPS-CMs; therefore, this technique will potentially be useful in predicting drug-induced arrhythmogenic liabilities in early de-risking within the drug discovery phase.

Topics: Action Potentials; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiotonic Agents; Cardiotoxins; Cardiovascular Agents; Cells, Cultured; Dose-Response Relationship, Drug; Humans; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Predictive Value of Tests

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

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

The majority of patients with Duchenne muscular dystrophy (DMD) have electrocardiographic abnormalities, but the clinical significance of conduction disturbances remains unclear. This study aimed to evaluate age-dependent cardiac conduction disturbances by electrocardiogram (ECG) to identify risks of complete atrioventricular (AV) block in this patient population.In total, 47 patients with DMD (age, ≥20 ys) who recorded ECGs at our hospital from July 2015 to June 2016 were included in this study. The PR interval and QRS duration in their previous ECGs were analyzed retrospectively. Associations between ECG findings and left ventricular (LV) systolic function obtained from the latest echocardiography were examined.The mean age of patients was 27.6 ± 6.0 years, and the mean observation period was 9.8 ± 3.7 years. The PR interval gradually increased with age, but no ECGs showed an abnormally prolonged PR interval. On the other hand, the QRS duration tended to increase progressively with age, and some patients had an abnormally prolonged QRS duration. The QRS duration was not correlated with LV systolic function (P = 0.867). One patient who developed a complete AV block had a drastically prolonged QRS duration before the onset of the disorder.The QRS duration tended to increase progressively with age, irrespective of LV systolic function in patients with DMD. Attention should be paid to the QRS duration as an indicator of risk for complete AV block in older patients.

Topics: Adult; Age Factors; Arrhythmias, Cardiac; Cardiovascular Agents; Disease Progression; Echocardiography; Electrocardiography; Humans; Male; Muscular Dystrophy, Duchenne; Retrospective Studies; Risk Factors; Ventricular Function, Left; Young Adult

Cardiac disease in SSc can manifest in various ways and is associated with a poor prognosis. There is little evidence on how best to detect and manage cardiac disease in SSc. Our objective was to produce an expert consensus best practice pathway for the management of cardiac disease in SSc.. The UK Systemic Sclerosis Study Group set up several working groups to develop a number of consensus best practice pathways for the management of SSc-specific complications, including cardiac disease. A multidisciplinary task force was convened. The guidelines were partly informed by a comprehensive literature review.. A best practice pathway for cardiac disease (with a focus on primary cardiac disease) in SSc is presented, including approaches for early detection and standard pharmacological and device therapies. Due to the benefits, shared care and a multidisciplinary approach are recommended. A future research agenda has been formulated in response to the relative lack of understanding of the natural history of primary cardiac disease that was highlighted by the initiative.. The physician should be alert to the possibility of cardiac disease in SSc; it is best managed within a multidisciplinary team including both rheumatologists and cardiologists. This pathway provides a reference for all physicians managing patients with SSc.

Topics: Arrhythmias, Cardiac; Biomarkers; Cardiomyopathies; Cardiovascular Agents; Electrocardiography; Evidence-Based Medicine; Heart Failure; Humans; Magnetic Resonance Angiography; Medical History Taking; Monitoring, Ambulatory; Patient Care Team; Pericarditis; Physical Examination; Risk Factors; Scleroderma, Systemic

: A 55-year-old gentleman with hypertrophic obstructive cardiomyopathy and heart failure symptoms underwent cardiac catheterization, which confirmed a significant pressure drop (60 mmHg) across the left ventricular outflow tract, a double-peaked pulse (pulsus bisferiens) and an absent postextrasystolic potentiation (Brockenbrough-Braunwald-Morrow sign) in the left ventricular outflow tract and the aorta. He was treated with medical therapy optimization and intracardiac defibrillator implantation. Cardiac catheterization may provide characteristic clues not only to diagnose obstructive hypertrophic cardiomyopathy, but also to understand its pathophysiological correlates.

Topics: Arrhythmias, Cardiac; Cardiac Catheterization; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Defibrillators, Implantable; Echocardiography; Electric Countershock; Electrocardiography; Hemodynamics; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Predictive Value of Tests; Treatment Outcome; Ventricular Function, Left; Ventricular Outflow Obstruction; Ventricular Pressure

Amitriptyline, a frequently used tricyclic antidepressant agent, has powerful cardiotoxic effects especially in high doses. Serum and urine levels of amitriptyline dosages are not correlated with severity of toxicity; therefore, it increases the importance of electrocardiography (ECG) abnormalities. The prolongation of QTc can be a predictive marker for cardiotoxicity. Hence, in this study, it is aimed to evaluate possible effects of metoprolol and diltiazem in amitriptyline toxicity.. The rats were separated into four groups. First one was control group, the second was the amitriptyline + saline group, third one was the amitriptyline + metoprolol group, and forth one was the amitriptyline + diltiazem group. ECG were recorded on rats under anesthesia.. In amitriptyline group, QTc duration was prolonged compared with all other groups. The prolongation of QTc was shorter in amitriptyline + metoprolol group and amitriptyline + diltiazem group than amitriptyline group (p < 0.01 and p < 0.01, respectively).. According to the results, it is possible to report ameliorating effects of both metoprolol and diltiazem on QTc prolongation related with amitriptyline intoxication. With further studies, these agents may be used for amitriptyline toxicity and besides, they may be used for patients in cardiovascular risk groups who take amitriptyline treatment regularly.

Topics: Amitriptyline; Animals; Antidepressive Agents, Tricyclic; Arrhythmias, Cardiac; Cardiovascular Agents; Diltiazem; Metoprolol; Rats

Serum digoxin levels have limited utility for determining digoxin toxicity in adults. Paediatric data assessing the utility of monitoring serum digoxin concentration are scarce. We sought to determine whether serum digoxin concentrations are associated with signs and symptoms of digoxin toxicity in children.. We carried out a retrospective review of patients 2 ng/ml).. There were 87 patients who met study criteria (male 46%, mean age 8.4 years). CHD was present in 67.8% and electrocardiograms were performed in 72.4% of the patients. The most common indication for digoxin toxicity was heart failure symptoms (61.5%). Toxic serum digoxin concentrations were present in 6.9% of patients (mean 2.6 ng/ml). Symptoms associated with digoxin toxicity occurred in 48.4%, with nausea/vomiting as the most common symptom (36.4%), followed by tachycardia (29.5%). Compared with those without toxic serum digoxin concentrations, significantly more patients with toxic serum digoxin concentrations were female (p=0.02). The presence of electrocardiogram abnormalities and/or signs and symptoms of digoxin toxicity was not significantly different between patients with and without serum digoxin concentrations (p>0.05).. Serum digoxin concentrations in children are not strongly associated with signs and symptoms of digoxin toxicity.

Topics: Adolescent; Age Factors; Arrhythmias, Cardiac; Cardiovascular Agents; Child; Child, Preschool; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Infant; Male; Nausea; Retrospective Studies; Texas; Vomiting

Elevated resting heart rate has been linked to poor outcomes in patients with chronic systolic heart failure. Blockade of funny current channel with ivabradine reduces heart rate without inotropic effects. Ivabradine was recently approved by US Food and Drug Administration for patients with stable, symptomatic chronic heart failure (HF) with left ventricular ejection fraction (LVEF) ≤35 %, who are in sinus rhythm with resting heart rate (HR) ≥ 70 bpm and either are on maximally tolerated doses of beta-blockers, or have a contraindication to beta-blockers. This article will review and evaluate the data supporting the use of ivabradine in patients with HF and explore its mechanisms and physiologic effects.

Topics: Arrhythmias, Cardiac; Benzazepines; Cardiomyopathies; Cardiovascular Agents; Clinical Studies as Topic; Heart Failure; Heart Rate; Heart Transplantation; Humans; Ivabradine; Shock, Cardiogenic; Ultrasonography

Preclinical and clinical studies have demonstrated that berberine (BBR) improves diabetic complications and reduces mortality of patients with congestive heart failure. The therapeutic effects of BBR have been reported to be mediated by its regulation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). We previously reported that BBR protects against ischemia-reperfusion injury via regulating AMPK activity in both ischemic and nonischemic areas of the rat heart. Since diabetic hearts are more sensitive to ischemia-reperfusion injury, we examined whether BBR treatment exhibited cardioprotective effects in the diabetic heart. Type 2 diabetic rats were pretreated plus or minus BBR for 7 days and subjected to 30-minute ischemia followed by 120-minute reperfusion. Pretreatment of type 2 diabetic rats with BBR reduced ischemia-reperfusion injury infarct size and attenuated arrhythmia compared to untreated diabetic controls. Subsequent to ischemia-reperfusion, serum triglyceride, total cholesterol, and malondialdehyde levels were reduced by pretreatment of type 2 diabetic rats with BBR compared to untreated diabetic controls. In contrast, serum glucose and superoxide dismutase levels were unaltered. The mechanism for the BBR-mediated cardioprotective effect was examined. Pretreatment with BBR did not alter AMPK activity in ischemic areas at risk but increased AMPK activity in nonischemic areas compared to untreated diabetic controls. The increased AMPK activity in nonischemic areas was due an elevated ratio of AMP to adenosine triphosphate (ATP) and adenosine diphosphate to ATP. In addition, pretreatment with BBR increased protein kinase B (AKT) phosphorylation and reduced glycogen synthase kinase 3β (GSK3β) activity in nonischemic areas compared to untreated diabetic controls. These findings indicate that BBR protects the diabetic heart from ischemia-reperfusion injury. In addition, BBR may mediate this cardioprotective effect through AMPK activation, AKT phosphorylation, and GSK3β inhibition in the nonischemic areas of the diabetic heart.

Topics: AMP-Activated Protein Kinases; Animals; Arrhythmias, Cardiac; Berberine; Biomarkers; Blood Glucose; Cardiovascular Agents; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Energy Metabolism; Enzyme Activation; Glycogen Synthase Kinase 3 beta; Lipids; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats, Wistar; Signal Transduction

α-Lipoic acid (LA) has been shown to offer protection against ischemia-reperfusion injury (IRI) in multiple organ systems. N-[(R)-1,2-dithiolane-3-pentanoyl]-L-glutamyl-L-alanine (CMX-2043), a novel analogue of LA, was studied as part of a preclinical development program intended to identify safe and efficacious drug candidates for prevention or reduction in myocardial IRI. This study was designed to evaluate the efficacy of CMX-2043 in an animal model of myocardial IRI and to establish effective dosing conditions. CMX-2043 or placebo was administered at different doses, routes, and times in male Sprague-Dawley rats subjected to 30-minute left coronary artery ligation. Fluorescent microsphere injection defined the area at risk (AR). Animals were euthanized 24 hours after reperfusion, and the hearts were excised, sectioned, and stained with triphenyltetrazolium. Cytoprotective effectiveness was determined by comparing the unstained myocardial infarction zone (MI) to the ischemic AR. The reduction in the MI-AR ratio was used as the primary measure of drug efficacy relative to placebo injections. Treatment with CMX-2043 reduced myocardial IRI as measured by the MI-AR ratio and the incidence of arrhythmia. The compound was effective when administered by injection, both before and during the ischemic injury and at reperfusion. The most efficacious dose was that administered 15 minutes prior to the ischemic event and resulted in a 36% (P < .001) reduction in MI-AR ratio compared to vehicle control.

Topics: Administration, Oral; Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Cytoprotection; Dipeptides; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Injections, Intravenous; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Rats, Sprague-Dawley; Thioctic Acid

The effectiveness of drug remaxol inclusion in the scheme of treatment of patients with myocardial infarction on the background of degree III - III acute cardiac insufficiency was evaluated by the analysis of clinical and laboratory data of 126 patients with newly diagnosed acute myocardial infarction including ST-segment elevation on the background of acute cardiac insufficiency. Depending on the regimen, patients were divided into two groups. The first (control) group included 60 patients who received conventional thrombolytic therapy; the second (main) group included 66 patients which, after thrombolytic therapy, received remaxol (single daily intravenous administration, 400 mL at 3 - 4 mL/min rate) with controlled central venous pressure, arterial pressure, and diuresis. The course lasted for 3 - 5 days, depending on the severity of condition. A high efficiency of the treatment regimen including remaxol was established as characterized by more rapid (in comparison to conventional therapy) stabilization of disturbed systemic hemodynamics and recovery of weakened myocardial contractility, decreased risk of cardiac arrhythmias, and relieved hyperhomocysteinemia that, in turn, reduced the risk of complications such as thrombosis and thromboembolism.

Topics: Aged; Arrhythmias, Cardiac; Blood Pressure; Cardiovascular Agents; Case-Control Studies; Drug Administration Schedule; Female; Fibrinolytic Agents; Heart Rate; Humans; Hyperhomocysteinemia; Injections, Intravenous; Male; Middle Aged; Shock, Cardiogenic; Succinates; Thromboembolism; Thrombolytic Therapy; Thrombosis; Treatment Outcome

Increasing evidence has demonstrated the potential risks of cardiac arrhythmias (such as prolonged QT interval) using tyrosine kinase inhibitors for cancer therapy. We report here that a widely used selective inhibitor of Src tyrosine kinases, PP2, can inhibit and prevent isoproterenol stimulation of cardiac pacemaker activity. In dissected rat sinus node, PP2 inhibited and prevented isoproterenol stimulation of spontaneous beating rate. In isolated sinus node myocytes, PP2 suppressed the hyperpolarization-activated "funny" current (If) by negatively shifting the activation curve and decelerating activation kinetics, associated with decreased cell surface expression and reduced tyrosine phosphorylation of hyperpolarization-activated cyclic nucleotide-modulated channel 4 (HCN4) channel proteins. In human embryonic kidney 293 cells overexpressing recombinant human HCN4 channels, PP2 reversed isoproterenol stimulation of HCN4 and inhibited HCN4-573x, a cAMP-insensitive human HCN4 mutant. Isoprotenrenol had little effects on HCN4-573x. These results demonstrated that inhibition of presumably tyrosine Src kinase activity in heart by PP2 decreased and prevented the potential β-adrenergic stimulation of cardiac pacemaker activity. These effects are mediated, at least partially, by a cAMP-independent attenuation of channel activity and cell surface expression of HCN4, the key channel protein that controls the heart rate.

Topics: Animals; Antineoplastic Agents; Arrhythmias, Cardiac; Cardiotonic Agents; Cardiovascular Agents; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Ion Channel Gating; Isoproterenol; Phosphorylation; Rats; Sinoatrial Node; src-Family Kinases

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

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

Heart rate slowing produced by cardiac parasympathetic (vagal) stimulation is thought to be the result of modulation of the acetylcholine-activated K(+) current (IK,ACh) and the pacemaker current (If) in sinoatrial (SAN) pacemaker cells. However, the contribution of these and other ion currents to vagal slowing is controversial. Here, we examined the contributions of IK,ACh and If to vagal slowing in 15 isolated, vagal-innervated preparations of guinea-pig atria, using 300 nM tertiapin-Q (TQ) and 2 μM ZD7288 to obtain full and substantial block of these currents, respectively. Blocking IK,ACh alone reduced atrial rate responses to 10-s trains of regular vagal stimulation (supramaximal stimulation, 2-ms duration, 1-10 Hz) by ~50% (P<0.01; N=11); blocking If alone had no effect (N=7). Blocking both IK,ACh and If produced ~90% reduction (P<0.01; N=4). Atrial cycle length response to a single burst of vagal stimuli (3 stimuli at 50 Hz), delivered at the optimum phase of the cycle was strongly suppressed by blocking IK,ACh (reduced by 98%; P<0.01; N=9), and modestly reduced by blocking If alone (by ~43%; P=0.20; N=6). The response was abolished by combined block of IK,ACh and If (P=0.04; N=4). Our data show that modulation of IK,ACh and If is sufficient to account for all the vagal slowing observed in this preparation. The vagally-induced negative shift in activation potential for If will be opposed by hyperpolarisation of SAN through activation of IK,ACh. Thus removal of IK,ACh by TQ may have exaggerated the overall contribution of If to vagal slowing.

Topics: Acetylcholine; Animals; Arrhythmias, Cardiac; Bee Venoms; Biological Clocks; Cardiovascular Agents; Cations; Disease Models, Animal; Guinea Pigs; Heart Rate; Parasympathetic Nervous System; Potassium; Potassium Channel Blockers; Pyrimidines; Sinoatrial Node; Vagus Nerve; Vagus Nerve Stimulation

The evaluation of proarrhythmic and hemodynamic liabilities for new compounds remains a major concern of preclinical safety assessment paradigms. Contrastingly, albeit functional liabilities can also translate to clinical morbidity and mortality, lesser preclinical efforts are focused on the evaluation of drug-induced changes in inotrope and lusitrope, particularly in the setting of concomitant hemodynamic/arrhythmic liabilities. This study aimed to establish the feasibility of an anesthetized guinea pig preparation to assess functional liabilities in the setting of simultaneous drug-induced electrocardiographic/hemodynamic changes, by evaluating the effects of various compounds with known cardiovascular properties on direct and indirect indices of left ventricular function. In short, twenty nine male guinea pigs were instrumented to measure electrocardiograms, systemic arterial pressure, and left ventricular pressure-volume relationships. After baseline measurement, all animals were given intravenous infusions of vehicle and two escalating concentrations of either chromanol 293B (n = 8), milrinone (n = 6), metoprolol (n = 7), or nicorandil (n = 8) for 10 minutes each. In all cases, these compounds produced the expected changes. The slope of preload-recruitable stroke work (PRSW), a pressure-volume derived load independent index, was the most sensitive marker of drug-induced changes in inotropy. Among the indirect functional indices studied, only the "contractility index" (dP/dtmax normalized by the pressure at its occurrence) and the static myocardial compliance (ratio of end diastolic volume and pressure) appeared to be adequate predictors of drug-induced changes in inotropy/lusitropy. Overall, the data confirms that both electrophysiological and mechanical liabilities can be accurately assessed in an anesthetized guinea pig preparation.

Topics: Anesthesia; Animals; Arrhythmias, Cardiac; Blood Pressure; Cardiovascular Agents; Cardiovascular System; Drug Evaluation, Preclinical; Electrocardiography; Feasibility Studies; Guinea Pigs; Heart Rate; Hemodynamics; Male; Myocardial Contraction; Toxicity Tests; Ventricular Function, Left

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

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

Insufficient correction of mechanical dyssynchrony is a cause of non-response to cardiac resynchronization therapy (CRT).. To determine if CRT delivery could be optimized during the implantation procedure by choosing the number and location of pacing sites using echocardiography guidance.. In patients with a QRS ≥ 150 ms or a QRS < 150 ms and criteria for mechanical dyssynchrony, the objective of the implantation procedure was to shorten the left pre-ejection interval (LPEI), measured online, by at least 10 ms compared with standard biventricular configuration, by moving the right ventricular (RV) lead at different locations and, if necessary, by adding a second RV lead.. Ninety-one patients (70 men; mean age 73 ± 10 years; left ventricular [LV] ejection fraction 29 ± 10%) were included. The final pacing configuration was standard biventricular in 15 (17%) patients, optimized biventricular in 22 (24%) and triple-site ventricular in 54 (59%). LPEI was shortened by ≥ 10 ms compared with standard biventricular stimulation in 73 (80%) patients. Compared with standard biventricular pacing, the final optimized pacing configuration improved global intraventricular synchrony (decreasing LPEI from 158 ± 36 ms to 134 ± 29 ms; P<0.001), LV systolic efficiency (decreasing LPEI/LV ejection time from 0.58 ± 0.18 to 0.46 ± 0.13; P<0.001) and LV filling (increasing LV filling time/RR from 44 ± 8% to 47 ± 7%; P<0.001) and decreased mitral valve regurgitation.. Intraoperative echocardiography-guided placement of RV lead(s) during CRT implantation is feasible and acutely improves LV synchrony compared with standard biventricular stimulation.

Topics: Aged; Arrhythmias, Cardiac; Cardiac Resynchronization Therapy; Cardiac Resynchronization Therapy Devices; Cardiovascular Agents; Combined Modality Therapy; Electrodes, Implanted; Female; Humans; Intraoperative Care; Male; Middle Aged; Prospective Studies; Prosthesis Implantation; Stroke Volume; Ultrasonography, Interventional; Ventricular Function, Left

Topics: Aged; Arrhythmias, Cardiac; Benzazepines; Cardiovascular Agents; Humans; Ivabradine; Male; Middle Aged; Multiple Organ Failure; Pilot Projects; Sepsis; Treatment Outcome

Topics: Arrhythmias, Cardiac; Cardiac Surgical Procedures; Cardiovascular Agents; Cyanosis; Diagnostic Techniques, Cardiovascular; Female; Humans; Hypoxia; Infant, Newborn; Male; Pacemaker, Artificial; Postoperative Complications; Pulmonary Valve Insufficiency; Respiration, Artificial; Tetralogy of Fallot

Inherited heart conditions are the most common cause of sudden cardiac death in those under the age of 35 and the leading cause of non-traumatic death in young athletes. Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease affecting 1 in 500 of the population. Some patients may exhibit severe left ventricular hypertrophy, others may show nothing more than an abnormal ECG. Left ventricular hypertrophy most commonly manifests in the second decade of life. Sudden death is rare and usually affects patients in the first three decades whereas older patients present with heart failure, atrial fibrillation and stroke. Arrhythmogenic right ventricular cardiomyopathy is a rare, autosomal dominant heart muscle disorder which affects between 1 in 1,000 and 1 in 5,000 of the population. Dilated cardiomyopathy (DCM) is characterised by a dilated left ventricle with impaired function that cannot be explained by ischaemic heart disease, hypertension or valvular heart disease. At least 25% of cases of DCM are familial. DCM may be associated with multisystem conditions such as muscular dystrophy. Chemotherapy and certain other drugs, alcohol abuse and myocarditis may also lead to a dilated and poorly contracting left ventricle. In many cases the first manifestation of an inherited cardiomyopathy can be a sudden cardiac arrest. Other presentations include chest pain or breathlessness during exertion, palpitations and syncope. In many of the cardiomyopathies, the diagnosis can be made with a standard ECG and echocardiogram. However if the diagnosis is not certain or the cardiologist wishes to look at the heart structure in greater detail, a cardiac MRI may be performed.

Topics: Adult; Arrhythmias, Cardiac; Cardiomyopathies; Cardiovascular Agents; Death, Sudden, Cardiac; Desmoplakins; Disease Management; Echocardiography; Electric Countershock; Electrocardiography; Female; Heart Rate; Humans; Magnetic Resonance Imaging; Male; Mutation; Myocardium; Syncope

Drug-induced torsades de pointes (TdP) and related clinical entities represent a current regulatory and clinical burden.. As part of the FP7 ARITMO (Arrhythmogenic Potential of Drugs) project, we explored the publicly available US FDA Adverse Event Reporting System (FAERS) database to detect signals of torsadogenicity for antipsychotics (APs).. Four groups of events in decreasing order of drug-attributable risk were identified: (1) TdP, (2) QT-interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. The reporting odds ratio (ROR) with 95 % confidence interval (CI) was calculated through a cumulative analysis from group 1 to 4. For groups 1+2, ROR was adjusted for age, gender, and concomitant drugs (e.g., antiarrhythmics) and stratified for AZCERT drugs, lists I and II (http://www.azcert.org , as of June 2011). A potential signal of torsadogenicity was defined if a drug met all the following criteria: (a) four or more cases in group 1+2; (b) significant ROR in group 1+2 that persists through the cumulative approach; (c) significant adjusted ROR for group 1+2 in the stratum without AZCERT drugs; (d) not included in AZCERT lists (as of June 2011).. Over the 7-year period, 37 APs were reported in 4,794 cases of arrhythmia: 140 (group 1), 883 (group 2), 1,651 (group 3), and 2,120 (group 4). Based on our criteria, the following potential signals of torsadogenicity were found: amisulpride (25 cases; adjusted ROR in the stratum without AZCERT drugs = 43.94, 95 % CI 22.82-84.60), cyamemazine (11; 15.48, 6.87-34.91), and olanzapine (189; 7.74, 6.45-9.30).. This pharmacovigilance analysis on the FAERS found 3 potential signals of torsadogenicity for drugs previously unknown for this risk.

Topics: Adverse Drug Reaction Reporting Systems; Amisulpride; Antipsychotic Agents; Arrhythmias, Cardiac; Benzodiazepines; Cardiotoxins; Cardiovascular Agents; Databases, Pharmaceutical; Death, Sudden, Cardiac; Female; Humans; Male; Olanzapine; Phenothiazines; Risk; Sulpiride; Tachycardia; Torsades de Pointes; United States; United States Food and Drug Administration; Ventricular Fibrillation

Drug-induced arrhythmia is one of the most common causes of drug development failure and withdrawal from market. This study tested whether human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) combined with a low-impedance microelectrode array (MEA) system could improve on industry-standard preclinical cardiotoxicity screening methods, identify the effects of well-characterized drugs, and elucidate underlying risk factors for drug-induced arrhythmia. hiPSC-CMs may be advantageous over immortalized cell lines because they possess similar functional characteristics as primary human cardiomyocytes and can be generated in unlimited quantities.. Pharmacological responses of beating embryoid bodies exposed to a comprehensive panel of drugs at 65 to 95 days postinduction were determined. Responses of hiPSC-CMs to drugs were qualitatively and quantitatively consistent with the reported drug effects in literature. Torsadogenic hERG blockers, such as sotalol and quinidine, produced statistically and physiologically significant effects, consistent with patch-clamp studies, on human embryonic stem cell-derived cardiomyocytes hESC-CMs. False-negative and false-positive hERG blockers were identified accurately. Consistent with published studies using animal models, early afterdepolarizations and ectopic beats were observed in 33% and 40% of embryoid bodies treated with sotalol and quinidine, respectively, compared with negligible early afterdepolarizations and ectopic beats in untreated controls.. We found that drug-induced arrhythmias can be recapitulated in hiPSC-CMs and documented with low impedance MEA. Our data indicate that the MEA/hiPSC-CM assay is a sensitive, robust, and efficient platform for testing drug effectiveness and for arrhythmia screening. This system may hold great potential for reducing drug development costs and may provide significant advantages over current industry standard assays that use immortalized cell lines or animal models.

Topics: Action Potentials; Adolescent; Arrhythmias, Cardiac; Cardiovascular Agents; Cells, Cultured; Drug Evaluation, Preclinical; Electric Impedance; Humans; Induced Pluripotent Stem Cells; Male; Microelectrodes; Myocytes, Cardiac; Tissue Array Analysis

We present here analysis of surgical treatment of 24 patients (5 women, 19 men, age 20-75, mean age 50.7 +/- 2.5 years) with dilated cardiomyopathy (DCM) operated during the period from 2008 to 2013. Duration of the disease ranged from 4 months to 12 years (mean 49.4 +/- 7.5 months). According to symptoms and results of 6-minute walk test 3 patients (13%) had heart failure NYHA class III and 21 patients (87%)--NYHA class IV. Average end-diastolic left ventricular size was 7.4 +/- 0.18 cm (6.0-9.2 cm), ejection fraction--26.7 +/- 2.1% (13-47%), mean pulmonary artery pressure 54.9 +/- 2.9 mm Hg (35-80 mmHg). All patients underwent organ-conserving surgery aimed at reverse remodeling of the heart. Surgery was accompanied with implantation of implantable cardioverter defibrillator in 3 patients and/or cardiac resynchronization therapy device in 6 patients. Two patients (8.3%) died during hospitalization of hemodynamically significant ventricular arrhythmias; seven patients (29.2%) died in the late postoperative period. The results of the analysis indicate that reverse-remodeling surgery may be effective in patients with DCM of any age group with preserved reserves of the liver, kidney, and lung function in the absence of active myocarditis. Further observations are needed to determine the place of this operation in the protocol of treatment of patients with DCM.

Topics: Arrhythmias, Cardiac; Cardiac Resynchronization Therapy; Cardiac Surgical Procedures; Cardiomyopathy, Dilated; Cardiovascular Agents; Defibrillators, Implantable; Female; Follow-Up Studies; Heart Function Tests; Humans; Male; Middle Aged; Moscow; Organ Sparing Treatments; Postoperative Complications; Postoperative Period; Survival Analysis; Treatment Outcome

The use of drugs is the subject of numerous recommendations. The purpose of this study was to evaluate the prevalence of drug-related sudden deaths (SD) and the possible changes during these past 20 years.. 271 patients, 205 men, 66 women aged from 12 to 88 years (mean 59 ± 15) were admitted after SD resuscitation outside the acute phase of myocardial infarction, 146 before 2000 (group I), 125 between 2000 and 2010 (group II). Complete check-up was performed.. Ischemic HD (41%) vs (37%), idiopathic dilated cardiomyopathy (12%) vs (11%), various HD (5%) vs (8%) were as frequent in groups I and II. Valvular HDs were more frequent in group I than II (12%) vs 6% (p<0.01). Abnormalities at ECG (preexcitation syndrome, conduction disturbance, atrial fibrillation or ion channel disorders) were less frequent in group I than II (8%) vs (18%) (p<0.02). Drug-facilitated or related SD's did not change in groups I and II: 54 patients presented a drug-related ventricular fibrillation or asystole, 16% in group I and 24% (NS) in group II. SD was caused by hypokalemia, QT interval increase or conduction disturbance. HD or abnormal ECG was present in 42 patients. Digoxin, diuretics, calcium inhibitors, betablockers, antiarrhythmic drugs alone or in association were mainly implicated.. Drug-related arrhythmias continue to explain or favour at least 20% of SDs. Despite numerous recommendations on the use of drugs, the prevalence of fatal events that may be attributed to a cardiovascular drug does not decrease between the years before 2000 and after 2000.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Cardiopulmonary Resuscitation; Cardiovascular Agents; Child; Death, Sudden, Cardiac; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prevalence; Time Factors; Young Adult

Topics: Arrhythmias, Cardiac; Cardiac Resynchronization Therapy; Cardiovascular Agents; Catheter Ablation; Defibrillators, Implantable; Heart Arrest; Humans

Sudden arrhythmic death syndrome (SADS) occurs when a person suffers a sudden, unexpected death, with no cause found at postmortem examination. We aimed to describe the cardiac screening outcomes in a population of relatives of SADS victims. Prospective and retrospective cohort study of consecutive families attending the Family Heart Screening clinic at the Mater Misericordiae Hospital in Dublin, Ireland, from January 2007 to September 2011. Family members of SADS victims underwent a standard screening protocol. Adjunct clinical and postmortem information was sought on the proband. Families who had an existing diagnosis, or where the proband had epilepsy, were excluded. Of 115 families identified, 73 were found to fit inclusion criteria and were retained for analysis, with data available on 262 relatives. Over half of the screened family members were female, and the mean age was 38.6 years (standard deviation 15.6). In 22 of 73 families (30%), and 36 of 262 family members (13.7%), a potentially inheritable cause of SADS was detected. Of the population screened, 32 patients (12.2%) were treated with medication, and 5 (1.9%) have received implantable cardiac defibrillators. Of the five families with long QT syndrome (LQTS) who had a pathogenic gene mutation identified, three carried two such mutations.. In keeping with international estimates, 30% of families of SADS victims were found to have a potentially inherited cardiac disease. The most common positive finding was LQTS. Advances in postmortem standards and genetic studies may assist in achieving more diagnoses in these families.

Topics: Adult; Arrhythmias, Cardiac; Autopsy; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Electrocardiography; Electrophysiologic Techniques, Cardiac; Exercise Test; Female; Genetic Predisposition to Disease; Genetic Testing; Heredity; Humans; Ireland; Male; Middle Aged; Pedigree; Phenotype; Predictive Value of Tests; Primary Prevention; Prospective Studies; Retrospective Studies; Young Adult

The microelectrode array (MEA) can be used to study extracellular field potentials (exFPs) of electrogenic cells. Microcontact printing, which must be repeated after each experiment, is often used to promote accurate positioning of cells onto electrodes. The present study used MEAs with evenly spaced detection electrodes aligning along permanent SU-8 topographical guidance channels to measure propagation direction and speed. Chronotropic agents, isoproterenol (ISO, 1 nM-1 mM), and verapamil (VP, 1 nM-10 μM); and potassium channel openers (KCOs), pinacidil (PIN), and SDZ PCO400 (SDZ), were used to characterize these MEA chips. ISO (1 mM) enhanced the propagation speed from 247.25 ± 50.58 μm/ms 381.29 ± 92.01 μm/ms (n = 9, p < 0.05), whereas VP (10 μM) reduced the propagation speed completely (n = 12, p < 0.001). PIN (1 mM) significantly reduced the propagation speed from 278.6 ± 43.7 μm/ms to 49.7 ± 27.7 μm/ms (n = 10, p < 0.001), whereas SDZ (1 mM) completely stopped the propagation (n = 9, p < 0.001). Both KCOs induced conduction pattern changes similar to those observed in cardiac arrhythmia. The MEA chips with SU-8 guidance channels may be used to study cardiovascular diseases that are related to conduction disruption.

Topics: Animals; Arrhythmias, Cardiac; Biomedical Engineering; Cardiovascular Agents; Cells, Cultured; Electrophysiological Phenomena; Membrane Potentials; Microelectrodes; Microscopy, Electron, Scanning; Myocytes, Cardiac; Potassium Channels; Rats

Cardiovascular drugs are used in pregnancy to treat maternal and fetal conditions. Mothers may also require drug therapy postpartum. Most cardiovascular drugs taken by pregnant women can cross the placenta and therefore expose the developing embryo and fetus to their pharmacologic and teratogenic effects. These effects are influenced by the intrinsic pharmacokinetic properties of a given drug and by the complex physiologic changes occurring during pregnancy. Many drugs are also transferred into human milk with potential adverse effects on the nursing infant. This article summarizes some of the literature concerning the risks and benefits of using cardiovascular drugs during pregnancy.

Topics: Abnormalities, Drug-Induced; Anti-Arrhythmia Agents; Anticholesteremic Agents; Anticoagulants; Arrhythmias, Cardiac; Cardiac Glycosides; Cardiovascular Agents; Female; Fibrinolytic Agents; Humans; Hypertension, Pregnancy-Induced; Maternal-Fetal Exchange; Platelet Aggregation Inhibitors; Pregnancy; Pregnancy Complications, Cardiovascular

To evaluate the long-term prognostic impact of baseline symptoms in a cohort of hypertrophic cardiomyopathy (HCM) patients.. We considered 84 HCM patients symptomatic at diagnosis: 26 (31%) with heart failure (group 1), 34 (40%) with syncope/palpitations (group 2) and 24 (29%) with chest pain (group 3). During a median follow-up of 102 (53-187) months, 25 (30%) patients died/underwent heart transplant (HTx), 14 of 26 (54%) in group 1, 10 of 34 (29%) in group 2 and one of 24 (4%) in group 3. At 12, 60 and 120 months, HTx-free survival rates were 100, 79 and 52% in group 1, vs. 100, 97 and 69% in group 2, vs. 96, 96 and 96% in group 3, respectively (P = 0.008). At multivariate analysis, heart failure [hazard ratio (HR) 2.59, confidence interval (CI) 95% 1.09-6.17, P = 0.032] and left atrium diameter (HR 1.83, CI 95% 1.16-2.89, P = 0.009) emerged as independent predictors of death/HTx, with incremental prognostic power with respect to echo Doppler variables of left ventricular systolic and diastolic dysfunction [area under the curve (AUC) of receiver operating characteristics (ROC) curves at 5 years: 0.90 vs. 0.78, respectively, P = 0.03].. Clinical presentation emerged as a relevant prognostic tool in HCM patients symptomatic at onset, as heart failure was associated with a particularly poor outcome. Heart failure and left atrium diameter at diagnosis showed incremental prognostic power compared with echo Doppler assessment of left ventricular systolic and diastolic dysfunction.

Topics: Adolescent; Adult; Aged; Arrhythmias, Cardiac; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Chest Pain; Chi-Square Distribution; Child; Child, Preschool; Disease-Free Survival; Echocardiography, Doppler; Female; Heart Atria; Heart Failure; Heart Transplantation; Humans; Infant; Italy; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Registries; Risk Factors; Syncope; Time Factors; Ventricular Function, Left; Young Adult

Dexrazoxane (DEX), an inhibitor of topoisomerase II and intracellular iron chelator, is believed to reduce the formation of reactive oxygen species (ROS) and protects the heart from the toxicity of anthracycline antineoplastics. As ROS also play a role in the pathogenesis of cardiac ischaemia/reperfusion (I/R) injury, the aim was to find out whether DEX can improve cardiac ischaemic tolerance. DEX in a dose of 50, 150, or 450 mg·(kg body mass)(-1) was administered intravenously to rats 60 min before ischaemia. Myocardial infarct size and ventricular arrhythmias were assessed in anaesthetized open-chest animals subjected to 20 min coronary artery occlusion and 3 h reperfusion. Arrhythmias induced by I/R were also assessed in isolated perfused hearts. Only the highest dose of DEX significantly reduced infarct size from 53.9% ± 4.7% of the area at risk in controls to 37.5% ± 4.3% without affecting the myocardial markers of oxidative stress. On the other hand, the significant protective effect against reperfusion arrhythmias occurred only in perfused hearts with the dose of DEX of 150 mg·kg(-1), which also tended to limit the incidence of ischaemic arrhythmias. It is concluded that DEX in a narrow dose range can suppress arrhythmias in isolated hearts subjected to I/R, while a higher dose is needed to limit myocardial infarct size in open-chest rats.

Topics: Acute Disease; Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Disease Models, Animal; Dose-Response Relationship, Drug; Electrocardiography; In Vitro Techniques; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Perfusion; Rats; Rats, Wistar; Razoxane; Reactive Oxygen Species; Treatment Outcome

Cardiovascular diseases (CVDs) are the main cause of morbidity and mortality all over the world. Acute myocardial infarction (AMI) is the leading cause of death and disability in the Iranian population. This prospective comprehensive study aimed to assess the clinical characteristics and in-hospital outcomes with possible correlations between them in patients with AMI.. From December 2009 to January 2011, patients admitted with ST-segment elevation myocardial infarction were included in this study. Patients' demographic data, drug history, prehospital delay, door-to-needle or door-to-balloon interval (time to order), type of intervention, presence of arrhythmia, hemodynamic parameters, Framingham risk score, electrocardiogram findings and laboratory data were recorded. Also the length of patients' hospitalization and in-hospital outcome were documented. The correlations between patients' baseline clinical data and in-hospital outcomes were investigated.. During the study period, 167 patients with a median age (range) of 61 (29-92) years were enrolled in our study. Patients' prehospital delay had the median (range) of 3 (0.5-48) h. Eighty-eight (52.7%) patients received streptokinase, for whom the median (range) of door-to-needle time was 30 (6-330) min. The door-to-balloon median (range) time of 44 (26.4%) patients treated with primary percutaneous coronary intervention (PCI) was 30 (60-300) min. Thirty-five (20.9%) patients were not eligible for thrombolysis or PCI due to late arrival (delay of more than 12 h). There were significant relationships between older ages of patients and occurrence of arrhythmia (P = 0.027), hypertension (P = 0.009) and consuming cardiovascular (P = 0.002) agents. In a multivariate analysis, younger individuals [odds ratio (OR) 0.036, 95% confidence interval (CI) 0.003-0.069] and those reperfused with primary PCI (OR 0.44, 95% CI 0.39-0.47) had significantly shorter hospital stays (discharged within a week).. Our results provide emphasis on prevention of cardiovascular risk factors and further support to decrease patients' prehospital delay and accelerate in-hospital interventions for patients with AMI.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Arrhythmias, Cardiac; Biomarkers; Cardiovascular Agents; Comorbidity; Coronary Angiography; Cross-Sectional Studies; Electrocardiography; Female; Fibrinolytic Agents; Hospitals, Teaching; Humans; Hypertension; Iran; Length of Stay; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Prospective Studies; Referral and Consultation; Risk Assessment; Risk Factors; Streptokinase; Thrombolytic Therapy; Time Factors; Time-to-Treatment; Treatment Outcome

Noncompaction myocardium (NCM) is a genetic heterogeneous primary cardiomyopathy which affects both children and adults and can be either isolated or combined with other congenital heart disorders. It has common pathogenesis of symptoms but is distinguished by pronounced clinical polymorphism. We have observed 25 adult patients (15 men, 10 women aged from 20 to 62 years, mean age 42.9+/-13.3 years) with NCM syndrome. Heart failure have been found in 96% of patients (functional class [FC] I in 7, II - in 6, III in 7, and IV - in 4 patients). Ninety two percent of patients have ventricular extrasystoles, 32% - atrial fibrillation, 28% - FC I-III angina. Mean end diastolic left ventricular dimension is 6.5+/-0.8cm, ejection fraction 29.7+/-13.0%, mean pulmonary artery pressure - 42.6+/-13.5 mm Hg. Intracardiac thrombosis have been found in 24% of patients. In 7 patients morphological study of myocardium has been performed. NCM syndrome was diagnosed at initial investigation just in 1 case. We distinguished the following clinical masks (variants of diagnosis) of NCM: 1) clinically not manifest, is revealed at accidental examination (4%); 2) exists under mask of "idiopathic" rhythm disturbances (8%); 3) has a mask of ischemic heart disease; 4) is revealed in patients with acute or subacute myocarditis (12%); 5) has a mask of dilated cardiomyopathy (52%); 6) NCM in patients with other primary cardiomyopathies (hypertrophic, restrictive, genetic myopathy, arrhythmogenic right ventricular dysplasia). Combination of NCM with congenital heart defects has been found in 20% of patients. In 56% of cases myocarditis was diagnosed (it was viral in no less than 44%). Only in 32% of patients it is possible to consider presence of isolated NCM syndrome. This paper contains discussion of problems of diagnostics (including morphological) and treatment in the presented group of patients, significance of myocarditis for development of decompensation, role of NCM in patients with other primary cardiomyopathies, possibility of compensatory (secondary) character of NCM in severe systolic dysfunction.

Topics: Adult; Arrhythmias, Cardiac; Biopsy; Cardiomyopathies; Cardiovascular Agents; Diagnosis, Differential; Disease Management; Electrocardiography; Female; Heart Defects, Congenital; Heart Failure; Heart Function Tests; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Myocarditis; Myocardium; Prognosis; Syndrome; Tomography, Spiral Computed; Treatment Outcome

Oxymatrine is one of the main alkaloid components extracted from SOPHORA roots and has been shown to play various protective roles in the cardiovascular system. The present study was designed to study the protective effect of oxymatrine on arrhythmias and their ionic channel mechanism. Rat arrhythmic models were established by aconitine injection and coronary artery ligation. Rat cardiomyocytes were acutely isolated, and the whole-cell patch clamp technique was employed to investigate the effects of oxymatrine on sodium channels. Pretreatment with oxymatrine markedly increased the dose of aconitine required to induce arrhythmias in rats. Additionally, oxymatrine significantly delayed the initial time and shortened the duration time of rat arrhythmias induced by coronary artery ligation. Cardiac mortality rate in coronary artery ligation-induced arrhythmias was also effectively decreased by oxymatrine in rats. The electrophysiological study showed that oxymatrine could significantly inhibit sodium and calcium currents in isolated rat cardiomyocytes in a concentration-dependent manner. In summary, oxymatrine plays a remarkably preventive role in rat arrhythmias through the inhibition of sodium and calcium currents.

Topics: Aconitine; Alkaloids; Animals; Arrhythmias, Cardiac; Calcium; Cardiovascular Agents; Coronary Vessels; Disease Models, Animal; Dose-Response Relationship, Drug; Myocytes, Cardiac; Phytotherapy; Plant Extracts; Plant Roots; Quinolizines; Rats; Rats, Wistar; Sodium; Sodium Channels; Sophora

Topics: Arrhythmias, Cardiac; Cardiology; Cardiotonic Agents; Cardiovascular Agents; Cardiovascular Surgical Procedures; Diffusion of Innovation; Heart Failure; Humans; Kidney Failure, Chronic; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Societies, Medical; Stem Cell Transplantation; Sweden; Therapies, Investigational

To assess the safety of long-term treatment with flecainide in patients with atrial fibrillation (AF), particularly with regard to sudden cardiac death (SCD) and proarrhythmic events.. Retrospective, observational cohort study.. Single-centre study at Örebro University Hospital, Sweden. Subjects.  A total of 112 patients with paroxysmal (51%) or persistent (49%) AF (mean age 60 ± 11 years) were included after identifying all patients with AF who initiated oral flecainide treatment (mean dose 203 ± 43 mg per day) between 1998 and 2006. Standard exclusion/inclusion criteria for flecainide were used, and flecainide treatment was usually combined with an atrioventricular-blocking agent (89%).. Death was classified as sudden or nonsudden according to standard definitions. Proarrhythmia was defined as cardiac syncope or life-threatening arrhythmia.. Eight deaths were reported during a mean follow-up of 3.4 ± 2.4 years. Compared to the general population, the standardized mortality ratios were 1.57 (95% confidence interval (CI) 0.68-3.09) for all-cause mortality and 4.16 (95% CI 1.53-9.06) for death from cardiovascular disease. Three deaths were classified as SCDs. Proarrhythmic events occurred in six patients (two each with wide QRS tachycardia, 1 : 1 conducted atrial flutter and syncope during exercise).. We found an increased incidence of SCD or proarrhythmic events in this real-world study of flecainide used for the treatment of AF. The findings suggest that further investigation into the safety of flecainide for the treatment of patients with AF is warranted.

Topics: Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrial Fibrillation; Cardiovascular Agents; Cohort Studies; Comorbidity; Death, Sudden, Cardiac; Female; Flecainide; Humans; Incidence; Male; Middle Aged; Patient Selection; Research Design; Retrospective Studies; Risk Factors; Sweden

Topics: Aged; Arrhythmias, Cardiac; Cardiovascular Agents; Defibrillators, Implantable; Echocardiography; Electrocardiography; Female; Genetic Predisposition to Disease; Heart Failure; Heart Ventricles; Humans; Isolated Noncompaction of the Ventricular Myocardium; Pulmonary Embolism

Surgical treatment of mitral stenosis (MS) usually consists of open mitral commissurotomy (MC) or percutaneous balloon MC, which require a cardiopulmonary bypass or transseptal approach, respectively. We describe here the first surgical management of congenital MS in a dog using a less invasive procedure, a surgical closed MC under direct echo guidance. A 5-year-old female Cairn terrier was referred for ascites, weakness, and marked exercise intolerance for 2 months, which was refractory to medical treatment. Diagnosis of severe MS associated with atrial fibrillation (AF) was confirmed by echo-Doppler examination and electrocardiography. Poor response to medical treatment suggested a corrective procedure on the valve was indicated. However, due to the cost and high mortality rate associated with cardiopulmonary bypass, a hybrid MC was recommended. A standard left intercostal thoracotomy was performed and three balloon valvuloplasty catheters of differing diameters were sequentially inserted through the left atrium under direct echo guidance. Transesophageal echocardiography revealed a 62% reduction in the pressure half-time compared to the pre-procedure. Thirteen months after surgery the dog is still doing well with resolution of ascites and a marked improvement of most echo-Doppler variables.

Topics: Animals; Arrhythmias, Cardiac; Cardiac Surgical Procedures; Cardiovascular Agents; Dog Diseases; Dogs; Echocardiography; Female; Mitral Valve Stenosis

A 5-year-old English Bulldog was presented for acute onset of syncope and fatigue caused by sustained ventricular tachycardia with left bundle block morphology and inferior axis. This arrhythmia had the electrocardiographic features of a ventricular tachycardia arising from the right ventricular outflow tract (RVOT), as described in an experimental canine model and in people. Since a RVOT aneurysm was identified by echocardiography, a segmental form of arrhythmogenic right ventricular cardiomyopathy (ARVC) was suspected. Gross examination of the heart confirmed the bulging of the RVOT and histological examination of the ventricular myocardium revealed segmental involvement of the RVOT with transmural fibro-fatty degeneration. To the authors' knowledge, this is the first reported case of AVRC in an English Bulldog and the first example of segmental AVRC described in the dog.

Topics: Animals; Arrhythmias, Cardiac; Cardiomyopathies; Cardiovascular Agents; Dog Diseases; Dogs; Fatal Outcome; Female; Ventricular Dysfunction, Right

This study was performed to clarify the present global clinical status, including medication(s) and social abilities, of adult patients with single ventricular physiology (SVP).. Clinical charts were retrospectively reviewed to evaluate the global clinical status, including functional capacity, medication(s), complications, and social activities of 68 adult patients with SVP aged 20-53 years (41 males); 50 had undergone the Fontan operation and they were divided into the young adult (25 patients) and adult Fontan groups. The others were cyanotic patients without the Fontan operation (non-Fontan group). Although the Fontan groups showed better functional capacity, higher arterial oxygen saturation and brain natriuretic peptide levels, and a better renal function, there was no difference in the cardiovascular events during follow-up between the 3 groups. The most frequent complication was arrhythmia without a significant group difference, although the non-Fontan group showed a high percentage of heart failure. Only 41 patients (60%) had a job and 8 (12%) were married.. Although the Fontan groups had favorable pathophysiological conditions, the high rate of cardiovascular events, as well as unsatisfactory social situations, indicate the importance of meticulous life-long management of patients with SVP, regardless of the type of surgical intervention.

Topics: Adult; Age Factors; Arrhythmias, Cardiac; Biomarkers; Cardiovascular Agents; Disease-Free Survival; Employment; Female; Fontan Procedure; Heart Defects, Congenital; Heart Failure; Heart Ventricles; Hemodynamics; Humans; Japan; Kaplan-Meier Estimate; Male; Marital Status; Middle Aged; Natriuretic Peptide, Brain; Palliative Care; Quality of Life; Retrospective Studies; Risk Assessment; Survivors; Time Factors; Treatment Outcome; Young Adult

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: Anesthetics, Local; Arrhythmias, Cardiac; Cardiovascular Agents; Fat Emulsions, Intravenous; Heart Arrest; Humans; Hypokalemia; Recurrence; Treatment Outcome

Topics: Advisory Committees; Angioplasty, Balloon, Coronary; Arrhythmias, Cardiac; Cardiology; Cardiovascular Agents; Clinical Trials as Topic; Emergency Medical Services; Hospitalization; Humans; Myocardial Infarction; Risk Assessment; Risk Reduction Behavior; Thrombolytic Therapy

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Clinical Trials as Topic; Digitalis Glycosides; Heart Failure; Humans; Morbidity

Acute cardiogenic shock is a lethal condition that results in death from myocardial failure, arrhythmia, or combinations of both. Aggressive medical, surgical, and interventional maneuvers have helped reduce the mortality. For the most advanced cases, ventricular assist devices have been used for persistent shock states. The purpose of this report is to describe the collaboration between cardiac surgery and cardiology subspecialty in an effort to promote native heart recovery in a complex case of cardiogenic shock requiring coronary artery bypass surgery, percutaneous coronary intervention, ventricular ablative therapy, and mechanical cardiac support.

Topics: Aged; Angioplasty, Balloon, Coronary; Arrhythmias, Cardiac; Cardiology; Cardiovascular Agents; Catheter Ablation; Coronary Artery Bypass; Heart-Assist Devices; Humans; Male; Myocardial Infarction; Patient Care Team; Shock, Cardiogenic; Stents; Thoracic Surgery

Topics: Aged, 80 and over; Arrhythmias, Cardiac; Cardiovascular Agents; Colitis, Ischemic; Colonic Neoplasms; Colonic Polyps; Colonoscopy; Digoxin; Drug Therapy, Combination; Female; Humans; Hypertension; Intestinal Mucosa; Nicardipine; Postoperative Complications; Propranolol; Risk Factors; Sigmoid Neoplasms

Topics: Adolescent; Advanced Cardiac Life Support; Airway Obstruction; Arrhythmias, Cardiac; Australia; Cardiovascular Agents; Catheterization; Child; Child, Preschool; Clinical Protocols; Electric Countershock; Electrocardiography; Heart Arrest; Heart Massage; Humans; Infant; Infant, Newborn; Intubation, Intratracheal; Monitoring, Physiologic; Oxygen Inhalation Therapy; Pediatrics; Respiration, Artificial

Topics: Arrhythmias, Cardiac; Cardiac Surgical Procedures; Cardiovascular Agents; Coronary Disease; Heart Failure; Humans; Myocardial Infarction

Sudden cardiac death is mainly caused by arrhythmic events, triggered by ischemia. About half of the affected persons had no previous diagnosis of coronary heart disease, thus rendering them practically unreachable for specific preventive measures. This fact makes it necessary to optimize reanimation conditions. The establishment of international reanimation standards (ILCOR) has stimulated an intensified scientific evaluation of therapeutic options. While the use of vasopressin, adrenaline and reanimation by bystanders is being evaluated at the moment, amiodarone has not fulfilled the expectation of reducing mortality. Secondary prevention of sudden cardiac death after cardiac events is based on betablockers, ACE inhibitors and antilipemic therapy. Guidelines on prevention of sudden cardiac death also recommend aldosterone blockade and n-3-fatty acids. Persons at highest risk gain most from the use of ICDs, yet it has not been shown that their use immediately after myocardial infarction reduces mortality.

Topics: Arrhythmias, Cardiac; Cardiopulmonary Resuscitation; Cardiovascular Agents; Cause of Death; Coronary Disease; Death, Sudden, Cardiac; Humans; International Cooperation; Practice Guidelines as Topic; Risk Assessment; Secondary Prevention; Survival Analysis

The Annual Scientific Sessions of the American Heart Association is the leading scientific conference in the cardiovascular field, both for basic and clinical research in cardiology and related disclipines. This report covers the outcome of major clinical trials that were presented in the 'late-breaking' clinical trial sessions. The Valsartan in Acute Myocardial Infarction Trial (VALIANT) investigated the angiotensin receptor blocker valsartan, the angiotensin-converting enzyme inhibitor captopril, and their combination in 14,703 survivors of an acute myocardial infarction with a reduced left ventricular ejection fraction on clinical outcome. The study demonstrated that valsartan and captopril where equally effective, whereas the combination was associated with an increased risk of side effects without further benefit. VALIANT is a landmark trial because it was the first large study that compared the combination of an angiotensin receptor blocker with an angiotensin-converting enzyme inhibitor in the setting of acute myocardial infarction. Other trials that will be summarised in this report are the Na + /H + Exchange Inhibition to Prevent Coronary Events in Acute Cardiac Conditions Trial (EXPEDITION; cariporide in coronary artery bypass graft surgery), the Reversal of Atherosclerosis with Aggressive Lipid Lowering Trial (REVERSAL; atorvastatin and pravastatin for atherosclerosis reversal), the Stroke Prevention Using an Oral Thrombin Inhibitor in Atrial Fibrillation V (SPORTIF V; ximelagatran and warfarin for stroke prevention in atrial fibrillation), the Prophylactic Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularisation (PAPABEAR; amiodarone for the prevention of postoperative atrial fibrillation), the Acute and Chronic Therapeutic Impact of a Vasopressin 2 Antagonist in Congestive Heart Failure (ACTIV in CHF; vasopressin 2 antagonist tolvaptan in congestive heart failure) and Prevention of Renal and Vascular Endstage Disease Intervention Trial (PREVEND IT; fosinopril and pravastatin in microalbuminuric subjects without hypertension or hypercholesterolemia).

Topics: American Heart Association; Arrhythmias, Cardiac; Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Guanidines; Humans; Sulfones; United States

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

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

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Diazepam; Drug Overdose; Female; Humans; Hydroxychloroquine; Hypokalemia; Hypotension

Topics: Angioplasty, Balloon, Coronary; Arrhythmias, Cardiac; Cardiovascular Agents; Clinical Trials as Topic; Emergency Medical Services; Health Promotion; Hospitalization; Humans; Myocardial Infarction; Risk Assessment; Thrombolytic Therapy; Time Factors; Ventricular Dysfunction

Reliable detection of drug-induced proarrhythmia, especially the potential for polymorphic ventricular tachycardia, is of great importance in the development of new compounds that are safe for the heart and was evaluated in a blinded study.. In 142 female rabbits, the monophasic action potential was used to determine intraventricular conduction, action potential duration (APD), triangulation (APD30 to APD90), reverse use-dependence, instability and presence of chaotic behavior, early afterdepolarizations, torsades de pointes (TdP), and ventricular fibrillation. In addition, 31 coded drugs were tested in a blinded fashion in another 150 hearts. Prototype cardiovascular agents [quinidine (IA), lidocaine (IB), flecainide (IC), propranolol (II), sotalol (IIIB), amiodarone (IIIAB) and verapamil (IV)] were correctly characterized in terms of their effects upon conduction and APD. Agents documented in clinical practice to have proarrhythmic potential (droperidol, sotalol, mibefradil, bepridil, lidoflazine, ketanserin, sertindole, terfenadine, haloperidol, astemizole, cisapride, ziprasidone, lubeluzole, dofetilide, quinidine, ibutilide) were identified as such. Pimozide is reported to rarely produce TdP and was also found to elicit Class III action with few adverse effects. Equally important, agents believed not to be proarrhythmic (two solvents, atenolol, propranolol, fenoximone, cetirizine, verapamil, sildenafil, lidocaine, diltiazem) were identified as having no proarrhythmic activity.. The SCREENIT method properly characterized and quantified prototype cardiovascular drugs and correctly identified proarrhythmic noncardiovascular agents of various mechanisms, but it did not produce false-positive results.

Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Electrophysiologic Techniques, Cardiac; Female; Heart; Heart Conduction System; Pharmaceutical Preparations; Rabbits

Topics: Anesthesia, Dental; Angina Pectoris; Arrhythmias, Cardiac; Cardiovascular Agents; Cardiovascular Diseases; Dental Care for Chronically Ill; Endocarditis, Bacterial; Humans; Medical History Taking; Physical Examination; Risk Factors; Vasodilator Agents

Topics: Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Cardiovascular Diseases; Humans; Thrombosis

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

Prolongation of action potential duration (APD) is considered a major antiarrhythmic mechanism (class 2I), but paradoxically, it frequently is also proarrhythmic (torsade de pointes).. The cardiac electrophysiological effects of 702 chemicals (class 2I or HERG channel block) were studied in 1071 rabbit Langendorff-perfused hearts. Temporal instability of APD, triangulation (duration of phase 3 repolarization), reverse use-dependence, and induction of ectopic beats were measured. Instability, triangulation, and reverse use-dependence were found to be important determinants of proarrhythmia. Agents that lengthened the APD by >50 ms, with induction of instability, triangulation, and reverse use-dependence (n=59), induced proarrhythmia (primarily polymorphic ventricular tachycardia); in their absence (n=19), the same prolongation of APD induced no proarrhythmia but significant antiarrhythmia (P<0.001). Shortening of APD, when accompanied by instability and triangulation, was also markedly proarrhythmic (primarily monomorphic ventricular tachycardia). In experiments in which instability and triangulation were present, proarrhythmia declined with prolongation of APD, but this effect was not large enough to become antiarrhythmic. Only with agents without instability did prolongation of APD become antiarrhythmic. For 20 selected compounds, it was shown that instability of APD and triangulation observed in vitro were strong predictors of in vivo proarrhythmia (torsade de pointes).. Lengthening of APD without instability or triangulation is not proarrhythmic but rather antiarrhythmic.

Topics: Action Potentials; Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Blood Pressure; Cardiovascular Agents; Cation Transport Proteins; Drug Evaluation, Preclinical; Electrocardiography; Ether-A-Go-Go Potassium Channels; Heart Rate; In Vitro Techniques; Male; Potassium Channel Blockers; Potassium Channels; Potassium Channels, Voltage-Gated; Predictive Value of Tests; Rabbits; Torsades de Pointes

Topics: Aged; Arrhythmias, Cardiac; Cardiovascular Agents; Diltiazem; Electrocardiography; Female; Humans

The role of prostaglandins in the antiarrhythmic effect of ischemic preconditioning (IP) was investigated in pentobarbital-anesthetized rats. In 5 unpreconditioned control rats, 30 min of occlusion of the left coronary artery elicited ventricular tachycardia (VT) and fibrillation (VF), with an average duration of VT and VF of 51 +/- 6 and 43 +/- 4 s, respectively. Frequent ventricular premature beats (VPBs; average 1,249 +/- 145) were also documented in these animals. Thirty minutes of reperfusion after the prolonged coronary occlusion in these animals caused more severe arrhythmias, including irreversible VF. In animals pretreated with IP (n = 5), which was achieved by 3 cycles of 3 min of occlusion followed by 5 min of reperfusion, 30 min of coronary artery occlusion caused neither VT nor VF, but occasional VPBs (average 2 +/- 1, p < 0.001 vs. control). Only occasional VPBs were observed during 30 min of reperfusion in this group. In animals pretreated with indomethacin (1 mg/kg i.v., n = 5) followed by IP, prolonged ischemia and reperfusion led to frequent VPBs but no VT or VF. The average number of VPBs during ischemia and reperfusion in this indomethacin-treated group was less than that of the controls but greater than the IP-only group (p < 0.01). In conclusion, prostaglandins appear to play a role in the protective effect of IP against VPBs during acute ischemia and reperfusion.

Topics: Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Electrocardiography; Heart Rate; Indomethacin; Ischemic Preconditioning, Myocardial; Male; Prostaglandins; Rats; Rats, Sprague-Dawley; Tachycardia, Ventricular; Ventricular Fibrillation

Cardiovascular drugs are the most often prescribed drug class in Germany. The objective of this study is to analyze the adverse drug reaction (ADR) profiles of these drugs and to identify some targets for prevention of ADR.. Since 1997 specially trained medical staff members of five Pharmacovigilance Centers in Germany prospectively screened all hospital admissions at the departments of internal medicine of five large teaching hospitals. ADR leading to hospital admission were registered and reported. Especially ADR caused by cardiovascular drugs and all factors, which could have been important for their occurrence were analyzed.. 559 of 2270 (24.6%) registered ADR cases were related to cardiovascular drugs. The drugs most frequently related to ADR were angiotensin inhibitors (17.9%), digitalis (17.3%), calcium channel blockers (13.9%), beta blockers (12.8%), and diuretics (12.2%). The most often observed ADR were arrhythmias (27.1%), syncopes and blood pressure dysregulations (25.1%), gastrointestinal symptoms (12.4%), and metabolic disorders (10.2%). 72% of patients were older than 65 years. Older patients were on a significantly higher number of drugs (6.2 +/- 2.4 vs 5.5 +/- 3.2; p < 0.001) than the younger ones. Furthermore, they were hospitalized significantly longer (13.2 +/- 9.9 vs 15.3 +/- 9.3 days; p < 0.01). Eleven patients (2%) died because of ADR due to cardiovascular drugs.. Cardiovascular drugs are frequently used. They are prescribed mainly to older patients. Often observed ADR can be prevented effectively by considering their indication, by a clear definition of the therapeutic target, by a dose adjustment to the individual clinical parameters of the patient and by regular control investigations. The large number of drug-induced rhythm disorders--in particular bradycardia--show that extraordinary attention should be paid to rhythm-affecting drugs. The detailed instruction of the patient about therapeutic aims, risks and a concrete guideline for the therapy/drug handling is generally necessary.

Topics: Adrenergic beta-Antagonists; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Calcium Channel Blockers; Cardiac Glycosides; Cardiovascular Agents; Diuretics; Drug Interactions; Female; Germany; Humans; Incidence; Male; Retrospective Studies; Syncope

The antiarrhythmic profile and cardiohemodynamic effect of a novel Ca(2+) channel blocker, 4-(5H-Dibenzo[a, d]cyclohepten-5-ylidene)-1-[(E)-3-(3-methoxy-2-nitro)phenyl-2-p ropeny l]piperidine hydrochloride (AH-1058), were analyzed using the epinephrine-, digitalis- and two-stage coronary ligation-induced canine ventricular arrhythmia models. Intravenous administration of AH-1058 (100 microg/kg) effectively suppressed each of the ventricular arrhythmias accompanied by weak hypotensive effects. The results contrast well with those of a typical Ca(2+) channel blocker, verapamil, which suppresses only the epinephrine-induced ventricular arrhythmia with severe hypotension. These results indicate that AH-1058 may possess a more selective inhibitory action on Ca(2+) channels in the heart than on those in the vessels. Furthermore, the antiarrhythmic actions of AH-1058 were slower in onset and longer-lasting, than those in our previous studies using other antiarrhythmic drugs, including Na(+) and Ca(2+) channel blockers. The antiarrhythmic effects of AH-1058 did not correlate with its plasma concentrations when administered either intravenously or orally. These results suggest that AH-1058 can become a long-acting Ca(2+) channel blocker with unique antiarrhythmic properties, and that AH-1058 may be used in certain pathological processes, for which selective inhibition of the cardiac Ca(2+) channels is essential.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Bridged Bicyclo Compounds; Calcium Channel Blockers; Cardiovascular Agents; Coronary Vessels; Digitalis; Disease Models, Animal; Dogs; Epinephrine; Ligation; Piperidines; Plants, Medicinal; Plants, Toxic

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 influence and mechanisms of action of N-ethyl- and N-benzyl-1,2-diphenylethanolamines (compounds E and B, respectively) on the arterial blood pressure and the heart rate of the rat together with their effects on CaCl2-induced arrhythmias in the rat were investigated. Both E and B in doses of (1.5-12 micromol/kg IV) decreased the arterial blood pressure and the heart rate in a dose-dependent manner. Studies with various receptor blockers, enzyme inhibitors and CaCl2 revealed that E-induced cardiovascular depressant effects were mainly due to CaCl2 channel blocking action and activation of cyclic guanylyl cyclase or release of NO whereas the cardiovascular effects of B seemed to involve both blockade of Ca2+ channels and activation of parasympathetic ganglia. Both compounds (12-14.5 micromol/kg) completely protected the rat against CaCl2 (60 mg kg(-1))-induced tachyarrhythmias. The B compound seemed to be several times more potent than the E compound in its cardiovascular depressant actions. The results suggest the potential usefulness of both compounds in the treatment of hypertension and supraventricular arrhythmias.

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Calcium Chloride; Cardiovascular Agents; Cardiovascular Diseases; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Ethanolamines; Heart Rate; Histamine H1 Antagonists; Histamine H2 Antagonists; Indomethacin; Male; Pyrilamine; Ranitidine; Rats; Rats, Wistar

Aminopeptidase P and angiotensin-converting enzyme (ACE) are responsible for the metabolism of exogenously administered bradykinin in the coronary circulation of the rat. It has been shown that ACE inhibitors decrease cytosolic enzyme release from the ischemic rat heart and reduce reperfusion-induced ventricular arrhythmias by increasing endogenous levels of bradykinin. It was hypothesized that the aminopeptidase P inhibitor apstatin could do the same. In an isolated perfused rat heart preparation subjected to global ischemia and reperfusion, both apstatin and ramiprilat (an ACE inhibitor) significantly decreased creatine kinase (CK) and lactate dehydrogenase (LDH) release. The difference between the postischemia and preischemia levels of released CK was reduced 68% by apstatin and 68% by ramiprilat compared with control. The corresponding reductions in LDH release were 74% for apstatin and 81% for ramiprilat. A combination of the inhibitors was not significantly better than either one alone. Apstatin and ramiprilat also significantly reduced the duration of reperfusion-induced ventricular fibrillation by 69 and 61%, respectively. The antiarrhythmic effect of apstatin was reversed by HOE140, a bradykinin B2-receptor antagonist, suggesting that apstatin is acting by potentiating endogenously formed bradykinin. The results demonstrate that the aminopeptidase P inhibitor apstatin is cardioprotective in this model of cardiac ischemia/ reperfusion injury.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Arrhythmias, Cardiac; Bradykinin; Cardiovascular Agents; Creatine Kinase; Drug Interactions; In Vitro Techniques; L-Lactate Dehydrogenase; Male; Peptides; Perfusion; Protease Inhibitors; Ramipril; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Ventricular Fibrillation

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

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

Oxyradicals have been implicated as a possible cause of reperfusion-arrhythmias (RA). However, the use of diverse exogenous oxyradical scavengers designed to reduce RA has given contradictory results. The aim of the present study was to determine whether enhancing the activity of the main endogenous enzyme involved in peroxide elimination in cardiac cells, namely glutathione peroxidase, may limit RA in isolated heart preparations by increasing their antioxidant status. For this purpose, a group of 15 male Wistar rats received a selenium enriched diet for ten weeks (1.5 mg Se/kg diet). Control animals (n = 15) received a standard diet containing 0.05 mg Se/kg diet. The incidence of early ventricular arrhythmias was investigated during the reperfusion period following 10 min regional ischemia induced ex-vivo by left coronary artery ligation. Our results show that selenium-supplementation significantly increased the global selenium status of the animals. In the isolated heart preparations, the selenium supplementation induced a significant reduction of the severity of RA as assessed by the arrhythmia score and the limitation of the incidence of both ventricular tachycardia (control: 91% vs selenium: 36%, p < 0.05) and irreversible ventricular fibrillation (control: 45% vs selenium: 0%, p < 0.05). These effects were associated with a significant increase in cardiac mitochondrial and cytosolic glutathione peroxidase activities in both the left and the right ventricles. These results illustrate the potential protective effect of selenium against ischemia-reperfusion injury and suggest that peroxides might play a key role in the genesis of some aspects of the reperfusion syndrome.

Topics: Administration, Oral; Animals; Arrhythmias, Cardiac; Body Weight; Cardiovascular Agents; Coronary Circulation; Dietary Supplements; Erythrocytes; Free Radicals; Glutathione Peroxidase; Heart; Heart Rate; Male; Myocardial Reperfusion Injury; Myocardium; Organ Size; Rats; Rats, Wistar; Reactive Oxygen Species; Selenium

The antiischemic and antiarrhythmic effects of alinidine and a number of novel alinidine analogs were examined by using perfused rat-heart models. In the isolated working rat heart, the alinidine analog TH91:21 (10 microM; a butyl derivative) significantly increased the postischemic recovery of the heart in terms of both power and efficiency when compared with the control group. In the in situ perfused heart model, this same compound, along with TH91:22 (10 microM; a pentyl derivative) also significantly reduced the severity of both ischemia- and reperfusion-induced arrhythmias in both paced and unpaced hearts. Thus this study is the first to demonstrate the potent antiarrhythmic efficacy of two novel alinidine analogs TH91:21 and TH91:22, with TH91:21 also demonstrated to be a potent antiischemic agent in the isolated working rat heart. Although the mode of action of these compounds remains unclear, results from this study suggest that it is not simply a result of bradycardia or blockade of KATP channels, two actions these compounds possess. These compounds thus possess a novel and beneficial pharmacologic profile worthy of further study.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Bradycardia; Cardiac Pacing, Artificial; Cardiovascular Agents; Clonidine; Heart; Male; Potassium Channel Blockers; Rats; Rats, Inbred WKY; Reperfusion Injury; Structure-Activity Relationship

To investigate the prevalence of and indications for digoxin use and the prevalence of beta blocker and calcium channel blocker use in older patients with previous myocardial infarction or coronary artery disease (CAD), and the prevalence of use of diuretics, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers in older patients with hypertension in an academic hospital-based geriatrics practice.. A retrospective analysis of charts from 528 unselected older patients, seen from June 1995 through July 1996 at an academic hospital-based geriatrics practice, was performed to investigate the prevalence of digoxin use and indications for digoxin use, the prevalence of beta blocker and calcium channel blocker use in older patients with previous myocardial infarction or coronary artery disease (CAD), and the prevalence of use of diuretics, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers in older patients with hypertension.. An academic hospital-based, primary care geriatrics practice staffed by fellows in a geriatrics training program and full-time faculty geriatricians.. A total of 416 women and 112 men, mean age 81 +/- 8 years (range 58 to 101), were included in the study.. Ninety-two of the 528 patients (17%) were taking digoxin. Recorded indications for digoxin were atrial fibrillation with or without congestive heart failure (CHF) in 39% of patients, CHF with sinus rhythm and abnormal left ventricular ejection fraction (LVEF) in 18% of patients, a clinical assessment of CHF with sinus rhythm and no recorded measurement of LVEF in 20% of patients, paroxysmal atrial fibrillation in 14% of patients, and coronary artery disease (CAD) in 9% of patients. Of 121 patients with previous myocardial infarction, 23 (19%) were prescribed beta blockers, and 54 (45%) were taking calcium channel blockers. Of 173 patients with CAD, 41 (24%) were treated with beta blockers, and 79 (46%) were taking calcium channel blockers. LVEF was not recorded in the charts of 90 of 121 patients (74%) with prior myocardial infarction and of 125 of 173 patients (72%) with CAD. Of 480 older patients with hypertension, 154 (37%) were treated with diuretics, 55 (13%) were treated with beta blockers, 160 (38%) were treated with ACE inhibitors, and 197 (47%) were treated with calcium channel blockers.. In 528 older patients seen in an academic hospital-based geriatrics practice, the prevalence of digoxin use was 19%. Appropriate indications for digoxin were documented clearly in the charts of 53 of 92 patients (57%). Calcium channel blockers were used more often than beta blockers in patients with previous myocardial infarction or CAD. Calcium channel blockers were the most frequently used antihypertensive drugs.

Topics: Academic Medical Centers; Adrenergic beta-Antagonists; Age Factors; Aged; Aged, 80 and over; Ambulatory Care Facilities; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Calcium Channel Blockers; Cardiovascular Agents; Coronary Disease; Digoxin; Diuretics; Drug Utilization; Female; Geriatrics; Heart Failure; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Retrospective Studies

To define the frequency and risk factors of cardiac arrhythmias during central venous catheter procedures in acute renal failure, continuous electrocardiographic monitoring with permanent recording was performed before and during 201 guidewire insertions in 171 patients requiring a central venous catheter for parenteral nutrition and/or dialysis access (121 procedures in 107 patients with acute renal failure; 39 procedures in 31 patients with normal renal function; 41 procedures in 33 patients with ESRD on chronic hemodialysis). No differences in cardiac arrhythmia frequencies were found during baseline recording. New arrhythmias were documented in 85 cases (85/201; 42%) during the catheter procedure. Ventricular arrhythmia frequencies increased significantly in all groups, as compared with baseline values (P < 0.05 for the control group, P < 0.01 for the chronic hemodialysis group, P < 0.001 for the acute renal failure group); the most noteworthy increase was observed in the acute renal failure group. Statistically significant differences among frequencies of total ventricular arrhythmias, advanced ventricular arrhythmias, and ventricular tachycardia during central venous catheter procedures were found between the acute renal failure group and both the normal renal function group (P < 0.05 to P < 0.001), and the chronic hemodialysis group (P < 0.05 to P < 0.01). All arrhythmias resolved spontaneously soon after partial guidewire withdrawal; nine episodes were symptomatic (in one case, ventricular tachycardia, followed by 10 s asystolia); no death directly related to the catheter procedure was observed. BUN and serum creatinine levels, as well as guidewire length remaining inside the patient, were significantly higher (P < 0.01) in patients with cardiac arrhythmias during central venous catheter procedures as compared with patients without arrhythmias; differences in other variables known as possible risk factors for arrhythmias (anatomical position, preexistent cardiac disease, utilization of proarrhythmogenic drugs, hypoxemia, acid-base status, and serum electrolytes, etc.) were not significant. Our study suggests that (1) patients with acute renal failure are at increased risk for cardiac arrhythmias during central venous catheter procedures; (2) an important risk factor is also represented by guidewire overinsertion, a technical error that should be avoided.

Topics: Acute Kidney Injury; Aged; Arrhythmias, Cardiac; Cardiovascular Agents; Cardiovascular Diseases; Catheterization, Central Venous; Female; Humans; Incidence; Male; Middle Aged; Prospective Studies; Risk Factors

We recorded heart rhythms of 40 older patients (20 medicated for cardiovascular disease and 20 not medicated for cardiovascular disease) during an outpatient oral surgery visit to determine overall arrhythmia incidence and severity, differences in incidence associated with cardiovascular medication status, and the impact of surgical intervention on arrhythmia incidence. We hypothesized that both groups would show similar arrhythmia numbers and types during surgical visits and that a history of medication for cardiovascular disease would not be an indicator of cardiac arrhythmia. Enrollment remained open until 20 patients older than 60 years of age from each group agreed to participate. Data were analyzed using the chi square statistic and Fisher's exact test (2-tailed). Included in the study were 24 women and 16 men; their mean age was 70.5 years (range, 60 to 86 years). Arrhythmias were detected in 17 patients and 33 of the 160 recorded rhythms. None of the detected arrhythmias were considered life-threatening. Significantly more arrhythmias occurred before administration of anesthesia than during administration of epinephrine-containing local anesthetics (p = 0.0001), and a greater number of rhythm disturbances were seen during the surgical procedure when compared with anesthesia administration (p = 0.0170). No differences in arrhythmia incidence were seen with increasing age, when male patients were compared with female patients, or when patients pharmacologically treated for cardiovascular disease were compared with patients not taking cardiovascular therapeutic medications. We conclude that although arrhythmias in this ambulatory population are common, they are typically benign in character and cardiovascular medication status is not indicative of their presence. In addition, minor oral surgery intervention with local anesthetics used in recommended dosages has no effect on cardiac arrhythmia status in the ambulatory geriatric population.

Topics: Aged; Aged, 80 and over; Ambulatory Surgical Procedures; Anesthesia, Dental; Anesthesia, Local; Anesthetics, Local; Arrhythmias, Cardiac; Cardiovascular Agents; Chi-Square Distribution; Dental Care for Aged; Epinephrine; Female; Geriatric Assessment; Humans; Incidence; Male; Middle Aged; Multivariate Analysis; Pilot Projects; Single-Blind Method; Stress, Physiological; Surgery, Oral; Vasoconstrictor Agents

Arrhythmias induced by coronary artery ligation in cats, by CaCl2 and epinephrine in rats, and by ouabain in guinea-pigs were used as experimental models for studying the effects of a new calcium antagonist AR-1 ([1,2,5-trimethyl-4-phenyl-4-beta-(N-cyanoethyl-N-4'-methoxybenzyl) -ethylamino]piperidine, calcium channel blocker and calmodulin antagonist) on ventricular arrhythmias. Coronary ligation caused 90% lethality (ventricular fibrillation) with 12.5 min in untreated control cats, which was prevented by administration of AR-1 (4 mg/kg body weight (b.w.) before or after arrhythmia induction. Pretreatment with AR-1 afforded protection in a dose-related fashion. A dose of 1.5 mg/KG b.w. increased survival to 45%, and all cats dosed with 3 to 5 mg/Kg b.w. survived. CaCl2 (180 mg/Kg b.w., i.v.) induced ventricular fibrillation and 100% lethality. These effects were completely prevented by an anti-arrhythmic dose of AR-1 (3 mg/kg b.w.). Epinephrine-induced ventricular arrhythmias were also prevented by the same dose of AR-1. AR-1 (5 mg/kg b.w.) did not prevent ouabain (0.5 mg/kg b.w.)-induced arrhythmias that caused death within 17 +/- 3.7 min, but displayed protective effects during 67 +/- 7.7 min. The results from these animal studies, in conjunction with previously studies demonstrating coronarodilatory and anti-platelet efficacy of this compound, collectively suggest that AR-1 has a potential to become a useful antianginal and antiarrhythmic therapeutic agent.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium Channel Blockers; Calcium Chloride; Cardiovascular Agents; Coronary Vessels; Electrocardiography; Epinephrine; Male; Ouabain; Piperidines; Rats; Rats, Wistar; Tachycardia, Ventricular; Ventricular Fibrillation

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

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

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: Adrenergic beta-Antagonists; Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Arrhythmias, Cardiac; Aspirin; Cardiovascular Agents; Heart Failure; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors

Emergencies in pediatric cardiology are heart failure, cyanosis and rhythm disturbances. The signs of heart failure are tachycardia, tachypnea and hepatomegaly. The therapy consists of oxygen, diuretics and digoxin. Occasionally, intubation with mechanical ventilation and intravenous catecholamines are needed. Cyanosis is often the only sign of a severe heart malformation, and prompt hospitalization is mandatory. Oxygen and warm environment is important during transport, correction of a possible metabolic acidosis and prostaglandin infusion are done in the hospital. Beyond the newborn period, so-called cyanotic spells are seen, particularly in tetralogy of Fallot. In supraventricular tachycardia, vagal manoeuvres can be tried first, if not successful, intravenous adenosine or electroconversion will restore sinus rhythm. In the older child, intravenous isoptin can be given. Slow heart rates from total AV block or sinus node affection are treated with atrophic, isuprel or electrical pacing.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Child; Child, Preschool; Combined Modality Therapy; Critical Care; Cyanosis; Drug Therapy, Combination; Heart Defects, Congenital; Heart Failure; Humans; Infant; Infant, Newborn

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

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

To evaluate the significance of clinical, hemodynamic and electrocardiographic risk factors in idiopathic dilated cardiomyopathy 94 patients were followed prospectively for 49 +/- 37 months. During follow-up, 30 patients died, 13 died suddenly, 13 died of congestive heart failure and 4 of other causes. Follow-up was completed in 85 patients, and overall cardiac mortality was 31%. Univariate analysis revealed left ventricular ejection fraction among 20 variables as the major indicator of risk of both cardiac death of all causes and sudden cardiac death separately. Multivariate overall analysis determined 3 independent risk factors in the following order for all causes of cardiac death: Ventricular pairs > 40/24 hours (RR 7.2, p < 0.0001), left ventricular ejection fraction < or = 35% (RR 6.5, p < 0.001) and first- or second-degree atrioventricular (AV) block (RR 3.1, p < 0.05). In the subset of patients with ejection fraction < or = 35% ventricular pairs > 40 per 24 hours (RR 10.7, p < 0.001), AV block (RR 3.9, p < 0.05), and the missing administration of vasodilators (RR 3.3, p < 0.05) were the most important. The chief risk factors for sudden cardiac death were age (RR 7.4, p < 0.01) and AV block (RR 4.6, p < 0.05) by adjustment for age, and ejection fraction < or = 35% (RR 7.1, p < 0.01) and AV block (RR 4.2, p < 0.05) if not adjusted for age. A differentiation into 4 risk groups was attempted. The additional independent prognostic importance of AV block was shown, especially in combination with reduced ejection fraction or a high incidence of ventricular pairs.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Arrhythmias, Cardiac; Atrial Fibrillation; Cardiomyopathy, Dilated; Cardiovascular Agents; Death, Sudden, Cardiac; Female; Follow-Up Studies; Heart Block; Hemodynamics; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Survival Analysis

This article discusses exercise testing in valvular heart disease, hypertension, and the evaluation of patients for surgery. It also provides information on the effects of drugs on the exercise test and the clinical significance of block patterns and arrhythmias encountered during exercise.

Topics: Arrhythmias, Cardiac; Cardiac Rehabilitation; Cardiovascular Agents; Cardiovascular Diseases; Coronary Disease; Disability Evaluation; Electrocardiography; Exercise Test; Heart Valve Diseases; Hemodynamics; Humans; Prognosis

The practice of pediatric cardiology has undergone remarkable changes over the past decade. Cardiac structural abnormalities may frequently be diagnosed with echocardiography alone, and treatment for many of these structural problems may be corrected during cardiac catheterization. Arrhythmia diagnosis and management have made similar progress, such that diagnosis of arrhythmia mechanisms and catheter ablative therapy may be performed during a single procedure, sparing the young patient a lifetime of antiarrhythmic drug therapy. Cardiac transplantation is now included among the treatment options for some patients with severe congenital or acquired cardiac abnormalities unresponsive to standard therapy. In this paper, we provide a brief description of current applications of recent advances in the practice of pediatric cardiology.

Topics: Arrhythmias, Cardiac; Cardiac Catheterization; Cardiovascular Agents; Echocardiography; Female; Fetal Monitoring; Heart Defects, Congenital; Heart Transplantation; Humans; Infant; Infant, Newborn; Male

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Coronary Disease; Electrocardiography; Heart Failure; Hemodynamics; Humans; Long-Term Care

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

Chronic cardiac failure with normal left ventricular systolic function is observed in conditions without ventricular failure (pericardial adiastole, obstruction to intracardiac blood flow) or with ventricular failure due to isolated abnormalities of left ventricular filling. These forms of cardiac failure are often subject to diagnostic error. However, it is essential that they be recognised because traditional therapy must be used with caution and because of the efficacy of treatment of the underlying pathology whenever this is possible.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Chronic Disease; Heart Failure; Humans; Ventricular Function, Left

Over 30 per cent of coronary patients die of cardiac failure excluding the acute phase of myocardial infarction. With the exception of preexisting hypertension, there is no compensatory hypertrophy in ischemic heart disease. However, hypertrophy is a costly adaptation in terms of myocardial oxygen demand and, therefore, coronary flow. Fibrous zones are unresponsive to inotropic drugs and so the treatment of cardiac failure due to ischemic heart disease consists in limiting or preventing episodes of ischemia. Each mechanism of ischemia has an appropriate treatment: the preload is reduced by trinitrin and its derivatives and by molsidomine; the after-load by calcium antagonists and angiotensin converting enzyme inhibitors; tachycardia and hypercontractile states by betablockers. The risk of arrhythmia, aggravated by many inotropic therapies, constitutes the major danger to ischemic heart failure; amiodarone, betablockers and preventive nitrate therapy are the most effective and least dangerous antiarrhythmics. Revascularisation is effective for permanently ischemic segments or for ischemia on effort but does not improve large plaques of fibrosis which sometimes require surgical ablation or plastic procedures. But these measures are incomplete if all aspects of the disease are not taken in consideration: loss of excessive body weight, exercise rehabilitation by modern techniques, limitation of bed rest at the ultimate stage of the disease allowing patients with ischemic cardiac failure a better quality of life without aggravating the prognosis.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Coronary Disease; Heart Failure; Humans; Myocardial Revascularization; Physical Exertion

The effect of neocuproine on cardiac injury was studied using retrogradely perfused isolated rat hearts in two experimental systems. In the first system, where hydrogen peroxide-induced damage was studied, neocuproine at the range of 40-175 microM provided protection at the level of 70-85%, as demonstrated by the reduced loss in the peak systolic pressure (P), in +dP/dt and in -dP/dt. In the second system, where ischemia/reperfusion-induced arrhythmias were studied, neocuproine (42 microM) provided a marked protection against cardiac injury as demonstrated by the lowering of the incidence in irreversible ventricular fibrillation, by decreasing the duration of ventricular fibrillation and by the concomitant increase of the duration of normal sinus rhythm, and by improving the post-ischemic recovery of P, +dP/dt and -dP/dt. Free radicals have already been implicated as causative agents in cardiac injury resulting from either hydrogen peroxide or ischemia followed by reperfusion. Additionally, iron and copper have already been shown to drastically exacerbate the injurious effects of free radicals. Thus, the results reported here with neocuproine, a highly effective chelator for both iron and copper, as well as with adventitious copper and with the combination of neocuproine and copper, are in accord with the mediatory role of transition metals in enhancing the deleterious effects induced by free radicals.

Topics: Animals; Arrhythmias, Cardiac; Blood Pressure; Cardiovascular Agents; Copper; Copper Sulfate; Coronary Circulation; Coronary Vessels; Heart Function Tests; Hydrogen Peroxide; In Vitro Techniques; Male; Myocardial Reperfusion Injury; Perfusion; Phenanthrolines; Random Allocation; Rats; Rats, Inbred Strains

The effects of OPC-88117, a new investigational antiarrhythmic drug, on early and delayed afterdepolarizations (EAD and DAD, respectively) were assessed in vitro in canine Purkinje fibers and in vivo in the canine right ventricle. OPC-88117 had similar electrophysiologic properties to class I antiarrhythmic agents in that it decreased Vmax. OPC-88117 decreased the amplitude and prolonged the coupling interval of DAD induced by acetylstrophanthidin. Likewise, OPC-88117 suppressed EAD induced in vitro by 4-aminopyridine. In vivo, cesium-induced EAD, ventricular arrhythmia, and atrioventricular block were suppressed by OPC-88117. In summary, OPC-88117 suppressed DAD and EAD in vitro and inhibited EAD and triggered activity in the in situ canine heart.

Topics: 4-Aminopyridine; Action Potentials; Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Cesium; Digitalis; Dogs; Electrocardiography; Heart; Heart Block; Heart Conduction System; Membrane Potentials; Piperazines; Plants, Medicinal; Plants, Toxic; Purkinje Fibers; Quinolones

Ten patients who presented with advanced heart disease and severe ventricular arrhythmia could be considered "at high risk of sudden death" caused by ventricular fibrillation. Yet they died suddenly while under Holter monitoring, and the recordings demonstrated that 4 of these deaths were due to a major disorder of conduction and 6 to ventricular fibrillation. Further analysis of these cases showed that the lethal disturbance of heart rhythm was ascribable to an anti-arrhythmic drug in 5 cases (2 with conduction disorder, 3 with ventricular fibrillation). It would appear that although patients of this kind need anti-arrhythmic drugs, these should be given with caution and in lower doses than in patients with normal left ventricular function.

Topics: Adult; Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Death, Sudden; Electrocardiography; Female; Humans; Iatrogenic Disease; Male; Middle Aged; Monitoring, Physiologic; Risk

A total of 349 patients with vasospastic angina were followed in eight centers in Japan for a period of 3.4 +/- 0.1 years (mean +/- SE). Ninety-eight percent of patients were treated with calcium blockers. Twenty-one episodes of myocardial infarction occurred in 18 patients (5%), including two fatal myocardial infarctions. The rate of myocardial infarction was higher (p less than .01) in patients with a fixed stenosis of 90% or greater than in patients with a fixed stenosis of less than 90% or normal coronary arteries. Myocardial infarctions occurred predominantly during hospital stays or at a time when the frequency of vasospastic angina increased. There were five sudden deaths (2%). Only one patient suffering sudden death had a fixed stenosis of 75% or greater. Serious arrhythmias were noted in 49 patients (14%). The risk of arrhythmias did not depend on the presence of a fixed stenosis of 75% or greater. These results suggest that cardiac events are rather infrequent in Japanese patients with vasospastic angina who are receiving treatment with calcium blockers and that the presence of a severe fixed stenosis markedly increases the risk of myocardial infarction but not the risk of arrhythmias.

Topics: Adult; Aged; Aged, 80 and over; Angina Pectoris; Arrhythmias, Cardiac; Calcium Channel Blockers; Cardiovascular Agents; Coronary Vasospasm; Death, Sudden; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Japan; Male; Middle Aged; Myocardial Infarction; Risk

Topics: Arrhythmias, Cardiac; Cardiotonic Agents; Cardiovascular Agents; Ductus Arteriosus, Patent; Humans; Infant, Newborn

The influence of chronically administered (6 weeks) herbicides (KAR, 2,4-D and 2,4,5-T) on pharmacological effects of quinidine, reserpine and strophantin K in mice and rats was examined in vivo. The investigated herbicides produced in mice an increase in acute toxicity of strophantin K, the acute toxicity of either reserpine oro quinidine being unchanged. The herbicides alone, after 6 weeks administration, significantly increased mean arterial pressure of rats, however the hypotensive response to reserpine was not statistically influenced in these animals as compared with controls. The prolonged administration of investigated herbicides produced also the increased sensibility of heart to the arrhythmic effects of quinidine and ouabain as observed in the ecg pattern in rats treated with increasing doses of these agents. The studies indicate the significance of the possible pharmacological interactions between the drugs affecting cardiovascular system and commonly used herbicides in men.

Topics: 2,4-Dichlorophenoxyacetic Acid; 2,4,5-Trichlorophenoxyacetic Acid; Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Drug Synergism; Herbicides; Male; Mice; Rats; Rats, Inbred Strains

Propranolol (0.5 mg X kg-1 X 5 min-1), alinidine (1 mg X kg-1 X 5 min-1) and the benzazepinon UL-FS 49 (0.5 mg X kg-1 X 5 min-1) were investigated in a canine model of exercise-induced transient myocardial dysfunction, mimicking exercise-induced functional impairment during angina pectoris in man. Each drug was infused intravenously, after two control treadmill exercise runs had shown comparable, ultrasonically assessed regional contractile dysfunction in an area supplied by a partly stenosed branch of the left coronary artery. All three drugs abolished exercise-induced regional contractile dysfunction. Propranolol and alinidine comparably decreased heart rate and positive dp/dtmax during exercise. UL-FS 49 showed a marked negative chronotropic effect without affecting positive dp/dtmax. Thus, prevention of exercise-induced regional contractile dysfunction has been shown for the first time using a selective bradycardic agent.

Topics: Animals; Arrhythmias, Cardiac; Benzazepines; Cardiovascular Agents; Clonidine; Dogs; Hemodynamics; Male; Myocardial Contraction; Physical Exertion; Propranolol

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

Ligation of the left anterior descending coronary artery was performed in open-chest anaesthetized rats and mortality as well as changes in ECG were evaluated for 30 min thereafter. Saline or drugs were administered 15 min prior to ligation. In the control group, following a 4 min lag period ventricular arrhythmias as single ectopic beats, ventricular tachycardia and ventricular fibrillation (VF) appeared, reaching a maximum between 10 and 20 min and disappearing after 30 min. Mortality (40% in the control group) coincided with the period of maximal arrhythmias, with VF more common in animals that died than in those surviving. Alinidine, a drug which reduces sino-atrial rate specifically but has no conventional antiarrhythmic properties, reduced mortality and VF. By means of order statistics the quantity 'risk of death' was used for evaluation of drug effects, considering incidence of death and VF as well as duration of VF. This quantity was reduced in correlation with the dose of alinidine (1-6 mg/kg i.v.) and in correlation with the reduction of heart rate. Mexiletine, an antiarrhythmic drug with membrane-depressant properties, also reduced the 'risk of death' dose dependently (1-10 mg/kg i.v.), but there was no correlation with a decrease in heart rate. It is suggested that alinidine reduced 'risk of death' by means of a reduced oxygen demand due to a decrease in heart rate.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Clonidine; Coronary Disease; Electrocardiography; Heart Rate; Hemodynamics; Male; Mexiletine; Rats; Rats, Inbred Strains; Risk; Ventricular Fibrillation

Iloprost (ILO) and ZK 96 480 (96 480) are stable prostacyclin (PGI2) analogues with platelet aggregation-inhibiting and hypotensive activities equal or superior to PGI2 which in contrast to PGI2 show longlasting pharmacological effects also after oral application. PGI2 as well as ILO and 96 480 with i.v. infusion at equihypotensive doses in rats after coronary artery ligation reduce ventricular ectopic beats, markedly reduce or abolish the periods of ventricular tachycardia and entirely prevent ventricular fibrilloflutter. Even nonhypotensive doses of the prostanoids attenuate postligation arrhythmias. Catecholamine depletion by reserpine pretreatment also markedly reduced the incidence of arrhythmias. As PGI2 and ILO have previously been shown by others to preserve noradrenaline content of sympathetic nerve terminals in ischemic myocardium, prevention of excessive catecholamine loss from hypoxically compromised sympathetic nerve terminals might be involved in the antiarrhythmic action of PGI2, ILO and 96 480.

Topics: Adenosine Diphosphate; Animals; Arrhythmias, Cardiac; Blood Pressure; Cardiovascular Agents; Epoprostenol; Iloprost; Lidocaine; Platelet Aggregation; Rats; Rats, Inbred SHR; Reserpine

Topics: Aged; Amyloidosis; Antihypertensive Agents; Arrhythmias, Cardiac; Body Weight; Cardiac Glycosides; Cardiovascular Agents; Cardiovascular Diseases; Cardiovascular System; Coronary Circulation; Coronary Disease; Heart Valve Diseases; Hemodynamics; Humans; Hypertension; Myocardial Contraction; Organ Size

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Digoxin; Drug Therapy, Combination; Electrocardiography; Furosemide; Humans; Hydrochlorothiazide; Male; Methyldopa; Middle Aged; Nitroglycerin; Potassium Chloride; Quinidine

Topics: Angina Pectoris; Anti-Arrhythmia Agents; Antihypertensive Agents; Arrhythmias, Cardiac; Cardiotonic Agents; Cardiovascular Agents; Cardiovascular Diseases; Fibrinolytic Agents; Hemodynamics; Humans; Hypertension; Platelet Aggregation; Thrombosis

Prompt defibrillation with lower energy levels (200 joules) initially is now recommended. Epinephrine is effective when instilled intratracheally and remains the treatment of choice for restoring cardiac rhythm. Enthusiasm for isoproterenol and calcium chloride has waned. Sodium bicarbonate and atropine are now used more cautiously. Bretylium and verapamil have improved the treatment of refractory ventricular fibrillation and paroxysmal supraventricular tachycardia, respectively.

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Electric Countershock; Heart Arrest; Humans; Male; Resuscitation; Tachycardia; Ventricular Fibrillation

Cardiovascular drugs, as a class, have low therapeutic indices, but also have great therapeutic potential. Plasma concentration information is therefore often of value when using these drugs. Unfortunately, the total plasma concentration may not reflect the concentration of pharmacologically active free drug, since a number of factors including disease states, heparin anticoagulation, non-linear binding characteristics, and in vitro artefacts can affect the protein binding of these agents. This may also explain their poor dose-response relationships and great interindividual variability in plasma concentration data. Careful studies relating bound and free drug concentration to pharmacological response may provide the clinician with a better guide to therapy, and enhance the usefulness of these drugs.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Binding Sites; Blood Proteins; Cardiovascular Agents; Disopyramide; Humans; Orosomucoid; Protein Binding; Quinidine

Prostacyclin (PGI2) can protect the heart against ischemia, i.e. it can reduce myocardial damage [9, 10]. PGI2 protects the myocardium in vivo by preventing platelets from clumping and by dispersing preformed platelet aggregates [1,14]. However, also in the absence of platelets, PGI2 was shown to protect the myocardium against ischemia at concentrations that did not affect smooth muscle tone in the vessel wall [2]. This protective effect of PGI2 in vitro might be related to a stabilization of cell membranes in adrenergic nerve endings and hence to the prevention of ischemia-induced catecholamine release [13]. The instability of PGI2, both in vitro and in vivo, limits its application during long ischemic periods. Recently, a stable prostacyclin analogue, ZK 36 374, was demonstrated to have several prostacyclin-mimetic activities, both in vitro and in vivo [11,12]. In this communication we report upon the beneficial effect of this stable prostacyclin analogue at a low concentration (4 nM) on the extent of ischemic damage, on the recovery of myocardial function and on the occurrence of arrhythmias in the isolated rat heart after 24 h hypothermic cardiac arrest.

Topics: Animals; Arrhythmias, Cardiac; Cardiovascular Agents; Coronary Circulation; Coronary Disease; Electrophysiology; Epoprostenol; Heart; Heart Arrest; Hypothermia, Induced; Iloprost; Male; Rats; Rats, Inbred Strains

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

This case is typical of cardiovascular drug regimens in the elderly. Indeed, patients are often on several additional drugs for cardiovascular problems as well as other diseases. Familiarity with the pharmacology of all drugs is mandatory. Interactions of drugs can be complex, and a clinical pharmacologist can be a helpful resource. The classic interaction in cardiovascular drug regimens, as in this case, is with the combination of digoxin and potassium-depleting diuretics. The special interactions of cardiovascular and psychotropic drugs will be discussed elsewhere in this symposium. General clinical concerns in the care of patients taking cardiovascular drugs include scrutiny of drug choice, dosage, and combination. The dosage of drugs may need to be altered as the client ages. Drug types and combinations also may need to be changed to meet the needs of the patient's altered physiologic responses. The patient's response to drug therapy must be continuously evaluated. The best rule is to ensure that the patient takes the least number of drugs at the minimum dose required for desired effects. Starting drug dosages low and increasing them gradually often prevent toxicity. The nurse's assessment of subtle behavior or physical changes is important for the early detection of toxicity and adverse reactions. The possibility that a noted change is drug precipitated should always be considered. Health education of the client, family, or appropriate others is a significant nursing contribution to care. Awareness of drug side effects and specific offsetting interventions can prevent many discomforts and complications. Often making the patient aware of his changing body needs helps to elicit cooperation.

Topics: Aged; Aging; Arrhythmias, Cardiac; Cardiovascular Agents; Coronary Disease; Female; Heart Failure; Humans; Hypertension; Kinetics; Middle Aged

Toxicity from cardiac drugs is a particular management challenge since the manifestations of an acute overdose and the initial indications for the drug are often similar. Plasma drug levels are essential but must be interpreted in light of the clinical picture. Hypotension, due to either vasodilatation or decreased myocardial contractility, and arrhythmias are the principal cardiac manifestations, but noncardiac effects are sometimes more troublesome. An antiarrhythmic agent of the same class should not be used in treating an arrhythmia resulting from an overdose.

Topics: Arrhythmias, Cardiac; Bretylium Compounds; Cardiovascular Agents; Cardiovascular Diseases; Digoxin; Disopyramide; Humans; Hypotension; Lidocaine; Liver; Phenytoin; Procainamide; Propranolol; Quinidine; Vasodilator Agents

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Dose-Response Relationship, Drug; Humans

The medicamentous therapy of the angina pectoris vera and of the chronic ischaemic heart disease is at present based on three groups of medicaments: nitrate compounds, beta-blocking agents and calcium antagonists. The underlying therapeutic principle which is common for them consists in the reduction of the oxygen requirement of the myocardium so that an improvement of the complaints and a larger load capacity may be achieved. The improvement may be objectified also at the behaviour of the haemodynamics and the ECG under load. The so-called coronary dilating remedies and the beta-stimulators did not prove clinically. In the acute attack rapidly acting nitroglycerin compounds remain the remedies of choice. Also the permanent treatment should at first again use longer acting nitrate preparations. When despite a sufficient dosage no satisfying improvement takes place an additional prescription of beta-blocking agents is recommended. Calcium antagonists are suitable particularly for the vasospastic form of the angina pectoris. They can be used also as basis medicaments, however, according to the hitherto yielded experiences they do not possess any advantages in contrast to the proved nitrates and beta-blocking agents. When apart from the ischaemic heart disease a hypertension exists, the beta-blocking agents are particularly indicated. This is further important for certain forms of tachycardiac disturbances of rhythm, which partly also well response to calcium antagonists. In patients with disturbances of conduction (sinus node and atrioventricular nodes, bifascicular block) beta-blocking agents are contraindicated. If there are no signs of cardiac decompensation and radiologically the heart proves to be normally large, so there is no indication for the prescription of glycosides.

Topics: Adrenergic beta-Antagonists; Angina Pectoris; Arrhythmias, Cardiac; Calcium; Cardiovascular Agents; Coronary Disease; Digitalis Glycosides; Humans; Nitroglycerin; Vasodilator Agents

The negative bathmo- ino and chronotropic effects of sparteine, butylsparteine and pentylsparteine were quantitatively determined in isolated rat atria. The antifibrillatory potency was studied in rats (aconitine arrhythmia), guinea pigs (digoxin arrhythmia) and in cats (spontaneous arrhythmia). In order to appraise the cardiovascular compatibility of these drugs, additional circulatory effects were studied in rats and cats. Acute toxicity following intravenous, intraperitoneal and oral administration was assessed in male and female mice. Pentylsparteine was more potent than sparteine and had a better therapeutic index.

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Female; Guinea Pigs; Heart; Hemodynamics; In Vitro Techniques; Lethal Dose 50; Male; Mice; Muscle Contraction; Rats; Sparteine

Topics: Adolescent; Ajmaline; Arrhythmias, Cardiac; Biomedical Research; Cardiovascular Agents; Dihydroergotoxine; Drug Therapy; Electrocardiography; Ergot Alkaloids; Humans; Neurocirculatory Asthenia; Rauwolfia

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Chemistry, Pharmaceutical; Drug Therapy; Electrophysiology; Heart; Humans; Metabolism; Pharmacology; Procainamide; Quinidine; Research

Topics: Ajmaline; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Hypnotics and Sedatives; Rauwolfia

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Drug Combinations; Pectins; Quinidine

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Cardiovascular Agents; Heart Conduction System; Humans

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Heart Arrest; Humans; Myocardial Infarction

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Humans; Quinidine

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Agents; Humans; In Vitro Techniques

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Butylamines; Cardiovascular Agents; Humans

Topics: Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Cardiovascular Agents; Digitalis; Heart Conduction System; Humans

Topics: Animals; Arrhythmias, Cardiac; Atropine; Cardiovascular Agents; Cats; Curare; Epinephrine; Heart Ventricles; Muscle Relaxants, Central

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Electrocardiography; Humans; Imidazolines; Muscle Relaxants, Central; Potassium

Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Calcium; Cardiovascular Agents; Procaine; Quinidine; Rats

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Digitalis; Humans; Poisoning

Topics: Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Cardiovascular Agents; Heart Conduction System; Humans

Topics: Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Cardiovascular Agents; Heart Conduction System; Humans

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Digitalis; Humans; Potassium; Tachycardia

Topics: Arrhythmias, Cardiac; Cardiovascular Agents; Digitalis; Potassium

Topics: Animals; Arrhythmias, Cardiac; Atrial Appendage; Atrial Fibrillation; Atrial Flutter; Cardiovascular Agents; Dihydroergotamine; Dogs; Ergot Alkaloids