cardiovascular-agents and Death--Sudden--Cardiac

Despite major advancements in cardiovascular medicine, sudden cardiac death (SCD) continues to be an enormous medical and societal challenge, claiming millions of lives every year. Efforts to prevent SCD are hampered by imperfect risk prediction and inadequate solutions to specifically address arrhythmogenesis. Although resuscitation strategies have witnessed substantial evolution, there is a need to strengthen the organisation of community interventions and emergency medical systems across varied locations and health-care structures. With all the technological and medical advances of the 21st century, the fact that survival from sudden cardiac arrest (SCA) remains lower than 10% in most parts of the world is unacceptable. Recognising this urgent need, the Lancet Commission on SCD was constituted, bringing together 30 international experts in varied disciplines. Consistent progress in tackling SCD will require a completely revamped approach to SCD prevention, with wide-sweeping policy changes that will empower the development of both governmental and community-based programmes to maximise survival from SCA, and to comprehensively attend to survivors and decedents' families after the event. International collaborative efforts that maximally leverage and connect the expertise of various research organisations will need to be prioritised to properly address identified gaps. The Commission places substantial emphasis on the need to develop a multidisciplinary strategy that encompasses all aspects of SCD prevention and treatment. The Commission provides a critical assessment of the current scientific efforts in the field, and puts forth key recommendations to challenge, activate, and intensify efforts by both the scientific and global community with new directions, research, and innovation to reduce the burden of SCD worldwide.

Topics: Cardiovascular Agents; Death, Sudden, Cardiac; Government; Health Facilities; Humans; Interdisciplinary Studies

The use of implantable cardioverter-defibrillators (ICDs) significantly reduces the risk of mortality in patients with heart failure with reduced ejection fraction (HFrEF). Current guidelines, which are based on seminal clinical trials published nearly 2 decades ago, recommend that patients be on optimal medical therapy for HF for a minimum of 3 months before referral for prophylactic ICD. This waiting period allows for left ventricular reverse remodelling and improvement in HF symptoms, which may render primary prevention ICD implantation unnecessary. However, medical therapy for HFrEF has significantly evolved since the publication of these landmark trials. Given the plethora of medical therapy options now available for HFrEF, it is appropriate to reassess the duration of this waiting period. In the present review, we examine the landmark randomised trials in primary prevention of sudden cardiac death in patients with HFrEF, summarise the novel medical therapies (sacubitril-valsartan, sodium-glucose cotransporter 2 inhibitors, ivabradine, vericiguat, and omecamtiv mecarbil) that have emerged since the publication of those trials, discuss the optimal timing of ICD referral, and review subtypes of nonischemic cardiomyopathy where timing of ICD insertion is guided by alternative criteria. With the steps now needed to optimise medical therapy for HFrEF, in terms of both classes of drugs and doses of each agent, it can easily take up to 6 months to achieve optimisation. Following that, waiting periods of 3 months for ischemic cardiomyopathy and 6 months for nonischemic cardiomyopathy may be required to allow adequate reverse remodelling before reevaluating for ICD implantation.

Topics: Cardiomyopathies; Cardiovascular Agents; Clinical Trials as Topic; Contraindications, Procedure; Death, Sudden, Cardiac; Defibrillators, Implantable; Heart Failure; Humans; Primary Prevention; Referral and Consultation; Stroke Volume

BACKGROUND Medical therapy for heart failure with reduced ejection fraction evolved since trials validated the use of implantable cardioverter-defibrillators (ICDs). We sought to evaluate the performance of ICDs in reducing mortality in the era of modern medical therapy by means of a systematic review and meta-analysis of contemporary randomized clinical trials of drug therapy for heart failure with reduced ejection fraction. METHODS AND RESULTS We systematically identified randomized clinical trials that evaluated drug therapy in patients with heart failure with reduced ejection fraction that reported mortality. Studies that enrolled <1000 patients, patients with left ventricular ejection fraction >40%, or patients in the acute phase of heart failure and study treatment with devices were excluded. We identified 8 randomized clinical trials, including 31 701 patients of whom 3631 (11.5%) had an ICD. ICDs were associated with a lower risk of all-cause mortality (relative risk [RR], 0.85; 95% CI, 0.78-0.94) and sudden cardiac death (RR, 0.49; 95% CI, 0.40-0.61). Results were consistent among studies published before and after 2010. In meta-regression analysis, the proportion of nonischemic etiology did not affect the associated benefit of ICD. CONCLUSIONS In our meta-analysis of contemporary randomized trials of drug therapy for heart failure with reduced ejection fraction, the rate of ICD use was low and associated with a decreased risk in both all-cause mortality and sudden cardiac death. This benefit was still present in trials with new medical therapy.

Topics: Aged; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Female; Heart Failure; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Recovery of Function; Risk Assessment; Risk Factors; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

Heart failure (HF) is one of the major challenges in the management of diabetes patients. Among subjects with diabetes, up to 20% could have HF. Conversely, diabetes prevalence in HF patients varies greatly from more than 10% up to 50%. When it is present, the risk of mortality and rehospitalization increases substantially. In addition, current evidence points to an increased risk of atrial fibrillation and sudden cardiac death in patients with diabetes. The inter-relation between diabetes cardiomyopathy, left ventricular hypertrophy, coronary artery disease and renal dysfunction indicates complex and intricate pathways. Despite the great value of clinical assessment and echocardiography, there is insufficient data to suggest systematic screening for HF in asymptomatic patients with diabetes. There is little evidence to indicate that improved glycaemic control improves HF outcome in this population. In the case of established HF, the general guidelines apply in diabetes patients. However, recent advances concerning glucose-lowering treatment in patients with cardiovascular disease suggest that the choice of glucose-lowering agent is of crucial interest and should be based on the patient's phenotype. New drug classes, such as SGLT2 inhibitors, seem to be of particular benefit in these patients. In the future, new personalized strategies should aim at not only good control of the glycaemic level but also the reduction and possibly the prevention of HF onset.

Topics: Atrial Fibrillation; Cardiovascular Agents; Death, Sudden, Cardiac; Diabetes Complications; Diabetic Cardiomyopathies; Heart Failure; Humans; Hypertrophy, Left Ventricular; Hypoglycemic Agents; Prevalence; Risk; Sodium-Glucose Transporter 2 Inhibitors

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

Hypertrophic cardiomyopathy is the most common inherited cardiovascular disease. It is characterized by increased ventricular wall thickness and is highly complex due to its heterogeneous clinical presentation, several phenotypes, large number of associated causal mutations and broad spectrum of complications. It is caused by mutations in sarcomeric proteins, which are identified in up to 60% of cases of the disease. Clinical manifestations of Hypertrophic Cardiomyopathy include shortness of breath, chest pain, palpitations and syncope, which are related to the onset of diastolic dysfunction, left ventricular outflow tract obstruction, ischemia, atrial fibrillation and abnormal vascular responses. It is associated with an increased risk of sudden cardiac death, heart failure and thromboembolic events. In this article, we discuss the diagnostic and therapeutic aspects of this disease.

Topics: Animals; Atrial Fibrillation; Cardiac Surgical Procedures; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Clinical Trials as Topic; Death, Sudden, Cardiac; Diagnostic Techniques, Cardiovascular; Drug Evaluation, Preclinical; Dyspnea; Genetic Association Studies; Heart; Heart Failure; Heart Septum; Heart Ventricles; Humans; Muscle Proteins; Pacemaker, Artificial; Penetrance; Risk Assessment; Sarcomeres; Syncope

Topics: Cardiac Surgical Procedures; Cardiology; Cardiovascular Agents; Clinical Decision-Making; Consensus; Coronary Vessel Anomalies; Death, Sudden, Cardiac; Evidence-Based Medicine; Genetic Predisposition to Disease; Humans; Percutaneous Coronary Intervention; Prevalence; Risk Assessment; Risk Factors; Treatment Outcome

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 improvements in the therapy of underlying heart disease, sudden cardiac death is a major cause of death worldwide. Disturbed Na and Ca handling is known to be a major predisposing factor for life-threatening tachyarrhythmias. In cardiomyocytes, many ion channels and transporters, including voltage-gated Na and Ca channels, cardiac ryanodine receptors, Na/Ca-exchanger, and SR Ca-ATPase are involved in this regulation. We have learned a lot about the pathophysiological relevance of disturbed ion channel function from monogenetic disorders. Changes in the gating of a single ion channel and the activity of an ion pump suffice to dramatically increase the propensity for arrhythmias even in structurally normal hearts. Nevertheless, patients with heart failure with acquired dysfunction in many ion channels and transporters exhibit profound dysregulation of Na and Ca handling and Ca/calmodulin-dependent protein kinase and are especially prone to arrhythmias. A deeper understanding of the underlying arrhythmic principles is mandatory if we are to improve their outcome. This review addresses basic tachyarrhythmic mechanisms, the underlying ionic mechanisms and the consequences for ion homeostasis, and the situation in complex diseases like heart failure.

Topics: Action Potentials; Calcium; Calcium Channels; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cardiovascular Agents; Death, Sudden, Cardiac; Electrocardiography; Epigenesis, Genetic; Excitation Contraction Coupling; Heart Conduction System; Homeostasis; Humans; Ion Channel Gating; Myocytes, Cardiac; Sodium; Sodium Channels; Tachycardia; Tachycardia, Ventricular

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

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

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

Diagnostics of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) are complex, and based on the 2010 Task Force document including different diagnostic modalities. However, recommendations for clinical management and follow-up of patients with ARVC and their relatives are sparse. This paper aims to give a practical overview of management strategies, risk stratification, and selection of appropriate therapies for patients with ARVC and their family members.. This paper summarizes follow-up and treatment strategies in ARVC patients in the Nordic countries. The author group represents cardiologists who are actively involved in the Nordic ARVC Registry which was established in 2009, and contains prospectively collected clinical data from more than 590 ARVC patients from Denmark, Norway, Sweden, and Finland.. Different approaches of management and follow-up are required in patients with definite ARVC and in genetic-mutation-positive family members. Furthermore, ARVC patients with and without implantable cardioverter defibrillators (ICDs) require different follow-up strategies.. Careful follow-up is required in patients with ARVC diagnosis to evaluate the need of anti-arrhythmic therapy and ICD implantation. Mutation-positive family members should be followed regularly for detection of early disease and risk stratification of ventricular arrhythmias.

Topics: Arrhythmogenic Right Ventricular Dysplasia; Cardiovascular Agents; Catheter Ablation; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Genetic Predisposition to Disease; Humans; Pedigree; Phenotype; Predictive Value of Tests; Risk Assessment; Risk Factors; Scandinavian and Nordic Countries; Treatment Outcome

The Brugada syndrome is a rare but well-defined cause of sudden cardiac death. The key underlying abnormality is a decrease in net depolarising current due to a genetic defect, though recent evidence also implicates structural abnormalities in some patients. Diagnosis requires a Brugada-type ECG as well as typical clinical features: such clinical considerations are currently key in guiding risk stratification and hence management. Whilst pharmacological therapies are under investigation, the only intervention with a robust evidence base remains insertion of an implantable cardioverter defibrillator. Further research will be required to allow more effective risk stratification and hence more rational therapy.

Topics: Brugada Syndrome; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Electrocardiography; Heart Conduction System; Heart Rate; Humans; Risk Assessment; Risk Factors; Treatment Outcome

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

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

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

Sudden cardiac death (SCD) is still a major public health issue with an estimated annual incidence ranging from 184,000 to > 400,000 per year. The ACC/AHA/ESC 2006 guidelines define SCD as "death from an unexpected circulatory arrest, usually due to a cardiac arrhythmia occurring within an hour of the onset of symptoms". A recent study of sudden cardiac death using multiple sources of ascertainment found that coronary artery disease was present in more than 50% of patients older than 35 years who died suddenly and underwent autopsy. Antiarrhythmic drugs have failed to show any mortality benefit even when compared to placebo or implantable cardiovertor defibrillators (ICDs). While patients with systolic heart failure are at higher risk of dying suddenly, most of the patients experiencing sudden cardiac death have left ventricular ejection fraction (LVEF) > 50%. β-blockers, Angiotensin enzymes (ACE) inhibitors as well as aldosterone antagonists prevent ischemia and remodelling in the left ventricle especially in post myocardial infarction (MI) patients and in patients with systolic heart failure. This article will review the data on the effects of traditional heart failure medications, especially β-blockers, Renin Angiotensin system blockers, as well as Statin therapy on sudden cardiac death in post MI patients and in patients with systolic heart failure.

Topics: Animals; Anti-Arrhythmia Agents; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Heart Failure; Humans; Incidence; Practice Guidelines as Topic

Heart failure is a highly prevalent disorder associated with increased mortality, repeated and lengthy hospitalization, and disability. Major progress has been made in the treatment of chronic heart failure associated with a reduced ejection fraction, through the development of neuromodulators such as angiotensin-converting-enzyme inhibitors, betablockers, angiotensin receptor blockers, mineralocorticoid receptor antagonists and, more recently, the bradycardic agent ivabradine. By contrast, little or no progress has been made in the management of acute heart failure or of heart failure with a preserved ejection fraction. New treatment modalities, including drugs, devices, and other novel approaches are currently being developed with the aim of reducing morbidity and/or mortality and improving the quality of life of patients with these disorders, which are a major burden for healthcare systems.

Topics: Benzazepines; Cardiac Resynchronization Therapy; Cardiotonic Agents; Cardiovascular Agents; Clinical Trials as Topic; Death, Sudden, Cardiac; Digitalis Glycosides; Disease Management; Drug Therapy, Combination; Heart Failure; Humans; Ivabradine; Multicenter Studies as Topic; Stroke Volume; Vasodilator Agents

Sudden cardiac death (SCD) is an uncommon but devastating potential consequence of participation in competitive sport. It is seen in adolescent and young adult athletes. The most common cause of this, hypertrophic cardiomyopathy (HCM), is a genetic disorder responsible for more than a third of cases and is manageable. Screening is undertaken for HCM, using differing strategies in Europe and North America. Screening and early diagnosis have reduced the mortality rate but has come at a significant economic cost. The evidence and relevant arguments for and against screening are presented together with management strategies as reflected by an illustrative case.

Topics: Adolescent; Athletes; Cardiomyopathy, Hypertrophic, Familial; Cardiovascular Agents; Death, Sudden, Cardiac; Genetic Testing; Heart Transplantation; Humans; Mass Screening; Risk Assessment; Risk Factors; Young Adult

In an aging population, major surgery is often performed in patients with complex co-morbidities. These patients present new risk constellations so that cardiac and respiratory complications mainly contribute to perioperative morbidity.. We composed a narrative review on pharmacological approaches to cardiovascular protection in the perioperative period including effects of central neuraxial blocks and hypothermia on cardiovascular outcome. The single chapters are structured as follows: pathophysiology-early studies-recent evidence-recommendations.. In coping with this challenge, innovative concepts like fast track surgery and pharmacological treatment are being utilized with increasing frequency including perioperative cardioprotection, novel strategies of anticoagulation or antiplatelet therapy, and protocols for postoperative pain therapy.. All the concepts described require an interdisciplinary approach in collaboration between operative physicians and physicians working in non-surgical disciplines like internal medicine, cardiology, and clinical pharmacology. The perioperative continuation of a pre-existing therapy with beta-blockers and other potentially cardioprotective agents like α(2)-agonists and statines is recommended. In the management of patients presenting for major surgery stratification of the perioperative risk is essential which considers both, invasiveness of the surgical procedure and conditions of the patient. Otherwise, side-effects might outweigh benefits of a potentially effective therapy as recently shown for the perioperative administration of beta-blockers that should be restricted to high-risk patients.

Topics: Cardiovascular Agents; Comorbidity; Cooperative Behavior; Coronary Thrombosis; Death, Sudden, Cardiac; Drug Therapy, Combination; Evidence-Based Medicine; Hospital Mortality; Humans; Interdisciplinary Communication; Length of Stay; Myocardial Infarction; Perioperative Care; Postoperative Complications; Risk Factors

Topics: Animals; Cardiovascular Agents; Cause of Death; Death, Sudden, Cardiac; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Electrocardiography; Female; Heart; Heart Failure; Humans; Long QT Syndrome; Male; Prognosis; Rabbits; Risk Assessment; Survival Analysis; Torsades de Pointes; Toxicity Tests

Concealed undiagnosed congenital anomalies of coronary arteries (CACA) can cause sudden death of young men. Isolated CACA are detected at 0.6-1.8% of coronary angiographies. Classification of CACA (2002) includes anomalous origin of coronary artery from pulmonary artery, anomalous origin of coronary artery from the aorta, congenital atresia of the left main coronary artery, coronary arteriovenous fistula, coronary artery with myocardial bridge, coronary artery aneurism, coronary artery stenosis. In most cases coronary artery anomalies for long time remain asymptomatic. Clinical picture of anomalous origin of coronary artery from pulmonary artery is often erroneously related to cardiomyopathy or myocarditis because of signs of heart failure. Modern methods of visualization are used for diagnosis of CACA: echocardiography (transthoracic and transesophageal), computer angiotomography (electron beam tomography, multispiral computer tomography), magnetic resonance angiography, thallium stress scintigraphy, single photon positron emission tomography, dobutamine stress echocardiography, endovascular ultrasound study. Coronary angiography is the gold standard for diagnosis of congenital anomalies of coronary arteries. Drug therapy, transluminal balloon angioplasty with stenting or surgical revascularization are indicated to patients with overt clinical picture.

Topics: Adult; Angioplasty, Balloon, Coronary; Asymptomatic Diseases; Cardiomyopathies; Cardiovascular Agents; Coronary Angiography; Coronary Vessel Anomalies; Death, Sudden, Cardiac; Diagnosis, Differential; Echocardiography; Heart Failure; Humans; Magnetic Resonance Angiography; Male; Myocarditis; Tomography, Spiral Computed; Young Adult

Hypertrophic cardiomyopathy (HCM) is the most common genetically transmitted cardiomyopathy. The underlying cause of HCM has been attributed to a number of mutations within genes encoding primarily for sarcomeric proteins, which lead to a heterogeneous phenotype of left ventricular hypertrophy in the absence of other causes (eg, hypertension, aortic stenosis, or a discrete membranous subaortic stenosis). Symptoms may range from mild to severely limiting and consist of dyspnea and chest pain with exertion or at rest, syncope, or even sudden cardiac death (SCD). The majority of patients with HCM are treated medically. The primary aim of therapy is to reduce symptoms, but it should also address the risk of SCD. Throughout the years, numerous medical treatments have been used to achieve symptom control in these patients, and include medications such as β-blockers, calcium channel blockers, amiodarone, disopyramide, and angiotensin receptor blockers. This review provides an overview of the current medical treatment of HCM.

Topics: Cardiomyopathy, Hypertrophic, Familial; Cardiovascular Agents; Death, Sudden, Cardiac; Genetic Predisposition to Disease; Humans; Mutation; Phenotype; Severity of Illness Index; Treatment Outcome

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

The management of patients with hypertrophic cardiomyopathy (HCM) has evolved markedly over the past 20 years, particularly with the rising number of indications for implantable cardiac defibrillators (ICDs) and alcohol septal ablation (ASA). However, medical therapies targeted to improve quality of life are underused; when resting and/or exercise obstruction is present, an incremental and additive approach should be used based on a high dosage of beta-blockers, verapamil and/or disopyramide. Radiofrequency catheter ablation of atrial fibrillation or A-V node has been proposed in some instances. Treatment of syncope or presyncope due to an abnormal blood pressure response during exercise remains challenging. Only patients with obstruction who remain severely symptomatic despite maximal medical therapy should be considered for invasive procedures, including dual-chamber (DDD) pacing, ASA or surgery. The reported complication rates of ASA (essentially complete A-V block, incidence above 5-10%, with mortality rates ranging from 0-4%) and the benefits at medium-term follow-up appear comparable to those observed after myectomy, which, according to guidelines, should remain the primary treatment for most severely symptomatic drug-refractory young patients with obstruction. While the overall survival of patients with HCM is similar to that of the general population, detection of patients at high risk of sudden cardiac death remains challenging, particularly in the young, and indications for ICDs in high risk patients without prior cardiac arrest should be patient- and family-orientated.

Topics: Cardiac Pacing, Artificial; Cardiology; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Catheter Ablation; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Embolization, Therapeutic; Ethanol; Heart Transplantation; Humans; Mitral Valve; Patient Selection; Quality of Life; Risk Assessment; Treatment Outcome

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

Alteration of neurohormonal homeostasis is a hallmark of the pathophysiology of chronic heart failure (CHF). In particular, overactivation of the renin-angiotensin-aldosterone system and the sympathetic catecholaminergic system is consistently observed. Chronic overactivation of these hormonal pathways leads to a detrimental arrhythmogenic remodeling of cardiac tissue due to dysregulation of cardiac ion channels. Sudden cardiac death resulting from ventricular arrhythmias is a major cause of mortality in patients with CHF. All the drug classes known to reduce mortality in patients with CHF are neurohormonal blockers. The aim of this review was to provide an overview of how cardiac ion channels are regulated by hormones known to play a central role in the pathogenesis of CHF.

Topics: Animals; Cardiovascular Agents; Chronic Disease; Death, Sudden, Cardiac; Heart Failure; Homeostasis; Humans; Ion Channels; Neurotransmitter Agents

The quintessential clinical diagnostic phenotype of human hypertrophic cardiomyopathy (HCM) is primary cardiac hypertrophy. Cardiac hypertrophy is also a major determinant of mortality and morbidity including the risk of sudden cardiac death (SCD) in patients with HCM. Reversal and attenuation of cardiac hypertrophy and its accompanying fibrosis is expected to improve morbidity as well as decrease the risk of SCD in patients with HCM.The conventionally used pharmacological agents in treatment of patients with HCM have not been shown to reverse or attenuate established cardiac hypertrophy and fibrosis. An effective treatment of HCM has to target the molecular mechanisms that are involved in the pathogenesis of the phenotype. Mechanistic studies suggest that cardiac hypertrophy in HCM is secondary to activation of various hypertrophic signaling molecules and, hence, is potentially reversible. The hypothesis is supported by the results of genetic and pharmacological interventions in animal models. The results have shown potential beneficial effects of angiotensin II receptor blocker losartan, mineralocorticoid receptor blocker spironolactone, 3-hydroxy-3-methyglutaryl-coenzyme A reductase inhibitors simvastatin and atorvastatin, and most recently, N-acetylcysteine (NAC) on reversal or prevention of hypertrophy and fibrosis in HCM. The most promising results have been obtained with NAC, which through multiple thiol-responsive mechanisms completely reversed established cardiac hypertrophy and fibrosis in three independent studies. Pilot studies with losartan and statins in humans have established the feasibility of such studies. The results in animal models have firmly established the reversibility of established cardiac hypertrophy and fibrosis in HCM and have set the stage for advancing the findings in the animal models to human patients with HCM through conducting large-scale efficacy studies.

Topics: Animals; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Death, Sudden, Cardiac; Drugs, Investigational; Fibrosis; Genetic Predisposition to Disease; Humans; Myocardium; Phenotype; Treatment Outcome

Use of device therapy to prevent sudden cardiac death in patients with heart failure is expanding on the basis of evidence from recent clinical trials. Three multicenter prospective clinical trials-Sudden Cardiac Death in Heart Failure (SCD-HeFT); Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION); and Cardiac Resynchronization-Heart Failure (CARE-HF)-were conducted to determine the effectiveness of devices in reducing mortality in patients with heart failure who did not have a history of ventricular arrhythmias. The 3 trials varied in the devices used, the population of patients included, and the study designs. In SCD-HeFT, implantable cardioverter defibrillators were more effective than pharmacological therapy in preventing mortality among patients with mild to moderate heart failure. In COMPANION, cardiac resynchronization therapy alone and cardiac resynchronization therapy plus an implantable cardioverter defibrillator were more effective than optimal drug treatment in reducing morbidity and all-cause mortality in patients with moderate to severe heart failure. In CARE-HF, cardiac resynchronization therapy alone was more effective than optimal drug treatment in reducing all-cause mortality in patients with moderate to severe heart failure. No direct comparison of the devices used has been done. These 3 clinical trials provide clear evidence that device therapy is beneficial for some patients with heart failure, even patients who do not have a history of ventricular arrhythmia.

Topics: Cardiovascular Agents; Critical Care; Death, Sudden, Cardiac; Defibrillators, Implantable; Heart Failure; Humans; Nurse's Role; Pacemaker, Artificial; Patient Education as Topic; Randomized Controlled Trials as Topic

Starting in the 1970s the hypothesis that the low mortality from coronary heart disease among the Greenland Eskimos was due to their high consumption of n-3 fish oil fatty acids, initiated many studies to find if the n-3 polyunsaturated fatty acids in fish oils (PUFAs) could prevent cardiac atherosclerosis. To date this possibility has not achieved clinical recognition. The recent literature shows an increase of intervention studies to learn if the fish oil fatty acids can reduce mortality from sudden cardiac death, and the mechanism(s) of such a protective effect. Indeed the most definite beneficial cardiac action of these n-3 PUFAs seems now to be their ability in the short term to prevent sudden cardiac death. It is apparent that over long periods of time the n-3 fish oil fatty acids also prevent atherosclerosis. Definition of the fatty acids to which I will be referring in the text: n-6 (omega-6) polyunsaturated fatty acids; linoleic acid (18:2n-6, LA); arachidonic acid (C20:4n-6, AA). n-3 (omega-3) fatty acids; alpha-linolenic acid (18:3n-3, ALA); eicosapentaenoic acid (20:5n-3, EPA); docosahexaenoic acid (C22:6n-3, DHA). The bold, underlined abbreviation will appear in the text to identify the fatty acid being discussed.

Topics: Animals; Atherosclerosis; Calcium Channels, L-Type; Cardiovascular Agents; Cardiovascular Diseases; Cells, Cultured; Death, Sudden, Cardiac; Dogs; Electrophysiology; Fatty Acids, Omega-3; Fish Oils; Humans; Myocytes, Cardiac; Rats

Recent guidelines have recommended more wide-ranging indications for the use of implantable cardioverter defibrillator (ICD) therapy, yet even more restrained previous guidelines have not been implemented for a variety of reasons.. This brief review critically examines the reasons most frequently put forward to explain this failure. Contrary to the frequently repeated speculation that the risk stratification for sudden death and hence prophylactic placement of ICDs is reasonably accurate, there is little cost difference between pharmacotherapy and ICD treatment over the long term. ICD therapy does not utilize an undue proportion of the healthcare budget, and the healthcare systems in Europe can afford this therapy.. Financial reasons are neither accurate nor adequate explanations for the failure of the European medical community to implement European guidelines for the implantation of ICDs for primary and secondary prevention of sudden cardiac death.

Topics: Cardiovascular Agents; Cost-Benefit Analysis; Death, Sudden, Cardiac; Defibrillators, Implantable; Drug Costs; Health Expenditures; Humans; Quality-Adjusted Life Years

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

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

Although the landscape of heart failure continues to rapidly evolve, and the widespread use of evidence-based pharmaceutical and device therapies has improved overall survival rates, mortality rates in heart failure patients remain high. Understanding the mode of death in heart failure is particularly important if we are to improve survival. This study reviews the evaluation of modes of death from heart failure and discusses the therapies, both pharmaceutical and device, that are useful in preventing these sequelae.

Topics: Adrenergic beta-Antagonists; Age Factors; Cardiac Output, Low; Cardiovascular Agents; Cause of Death; Death, Sudden, Cardiac; Female; Humans; Male; Randomized Controlled Trials as Topic; Survival Rate; Systole

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

The authors review the rapidly expanding knowledge relating to the arrhythmogenic (torsadogenic) effects of non-antiarrhythmic drugs that lengthen ventricular repolarization (i.e. the duration of electrocardiographic QT interval). After outlining the ECG characteristics and electrophysiological mechanism of drug-induced long-QT syndrome and torsades de pointes ventricular tachycardia, they discuss the concept of repolarization reserve and its role in arrhythmogenesis. Information is provided on the cardiac ion channel background of the proarrhythmic action of QT-prolonging non-antiarrhythmic drugs. The authors present pharmacoepidemiological data on the clinical importance and incidence of this peculiar adverse drug reaction that can in certain cases cause sudden arrhythmic death. They draw attention to the predisposing factors of torsades de pointes ventricular tachycardia, and list those groups of drugs and individual agents that have QT-lengthening and torsadogenic side-effects.

Topics: Action Potentials; Anti-Bacterial Agents; Antidepressive Agents, Second-Generation; Cardiovascular Agents; Death, Sudden, Cardiac; Electrocardiography; Heart Conduction System; Humans; Long QT Syndrome; Psychotropic Drugs; Risk Factors; Torsades de Pointes

Calstablin2 stabilises the ryanodine receptor (RyR2), preventing aberrant activation of the channels during the resting phase of the cardiac muscle. Loss of this stabilisation may be associated with cardiac arrhythmias, the sudden death occasionally observed in people with structurally normal hearts, as well as the atrial fibrillation in heart failure. Calstabin2-deficient mice have structurally normal hearts but exhibit exercise-induced cardiac ventricular arrhythmias that cause sudden death. In arrhythmias, the calstabin2 stabiliser JTV519 did not prevent arrhythmias in calstabin2-/- mice, but reduced the arrhythmias in calstabin2+/- mice, illustrating the antiarrhythmic potential of stabilising calstablin2. Familial polymorphic ventricular tachycardia in humans has been linked to missense mutants in the hRyR2 gene. In HEK293 cells, these RyR2 mutants showed less binding of 35S-calstabin2 than the wild type, indicating a reduced binding affinity. In human atrial fibrillation and heart failure, where there is excessive disassociation of calstabin2 from the RyR2 receptor in vitro, JTV519 is able to reverse this. In conclusion, calstabin2 is an important new target in sudden cardiac death associated with structurally normal hearts, and in the treatment of atrial fibrillation and heart failure.

Topics: Animals; Cardiovascular Agents; Death, Sudden, Cardiac; Diltiazem; Humans; Tacrolimus Binding Proteins; Thiazepines

Current guidelines define the standard of care for patients after myocardial infarction (MI), with particular focus on patients with significant ventricular dysfunction. Inherent in these recommendations are assumptions about the relative risks and benefits, as well as the costs, of the available options. This review will consider strategies to prevent sudden death and heart failure post-MI by utilization of pharmacologic therapies--angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), aldosterone antagonists, statins, and beta-blockers--in parallel with the approaches reviewed elsewhere in this supplement. A patient-centric approach necessitates that drugs in each class be compared for efficacy within this patient population. Clinical trials have demonstrated the efficacy of several drugs, such as ACE inhibitors, beta-blockers, and aldosterone antagonists, in patients post-MI, yet these benefits do not seem to be reflected in the epidemiologic data. This may reflect underutilization of these therapies or, alternatively, support the notion that efficacy in clinical trials does not assure effectiveness in clinical practice. The latter point is a subject of ongoing investigation, while the former is being addressed through quality-of-care initiatives. In clinical practice, aggressiveness is key, starting with patient education. If patients understand their risks better, compliance and adoption of a more ideal lifestyle seem more likely. However, even with educational programs, human nature teaches us that marked change in behavior is difficult and therefore, to minimize risks, particularly of sudden death and heart failure post infarction, an optimized pharmacologic regimen serves as a powerful tool.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Death, Sudden, Cardiac; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mineralocorticoid Receptor Antagonists; Myocardial Infarction; Risk Factors; Risk Reduction Behavior

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

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

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

Women who experience heart failure (HF) exhibit distinct differences from men. Because women are a minority in major HF trials and because diagnostic criteria have been variable in epidemiologic surveys, many questions remain unanswered. This article describes differences in sex hormone effects and responses to injury, pressure overload, and aging, which may account for differences observed in epidemiology, risk factors and causes, mechanisms for disease development, response to treatment, and outcomes. Hypertension,diastolic dysfunction, diabetes, obesity, and inactivity are more important factors in women, whereas ischemic heart disease and systolic dysfunction are more important factors in men. Women appear to benefit less from established treatments but have better survival. Future studies directed exclusively at women may be warranted to confirm or establish benefits of existing and future treatments.

Topics: Adult; Age Distribution; Aged; Cardiovascular Agents; Cause of Death; Clinical Trials as Topic; Coronary Disease; Death, Sudden, Cardiac; Epidemiologic Studies; Female; Gonadal Steroid Hormones; Heart Failure; Humans; Hypertension; Middle Aged; Patient Selection; Prognosis; Risk Factors; Sex Characteristics; Sex Distribution; Sex Factors; Survival Rate; Treatment Outcome; United States; Women's Health

Hypertrophic cardiomyopathy (HCM) is a relatively common disease of the cardiac sarcomere with broad heterogeneity in terms of the disease-causing gene mutation, phenotypic expression, therapy and prognosis. Besides the standard drug treatment, there are several therapeutic options available for severe refractory symptomatic HCM with obstruction. Dual-chamber pacing and transcoronary ablation of septal hypertrophy (TASH) have recently emerged as alternatives to myectomy. However, myectomy remains the current gold standard of therapy for HCM until the promising initial follow-up data for TASH can be transferred into a long-term follow-up period, or prospective randomized comparative trials between these therapies are available. However, even now, TASH represents an important therapeutic alternative in patients with relevant co-morbidities and a high operative risk. Despite significant gradient reduction and amelioration of clinical symptoms, none of these treatment strategies has a proven influence on the natural history of HCM. Hence, regarding the long-term prognosis of the disease, risk stratification of sudden cardiac death using non-invasive risk assessment has become of paramount importance, while genotyping might become the determinant and stratifying marker in the near future. At present, according to secondary prevention, treatment with an implanted cardioverter-defibrillator +/- amiodarone therapy is mandatory, while according to primary prevention treatment should particularly depend on the individual risk profile.

Topics: Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Combined Modality Therapy; Death, Sudden, Cardiac; Defibrillators, Implantable; Heart Septum; Humans; Minimally Invasive Surgical Procedures; Pacemaker, Artificial; Survival Rate; Ventricular Outflow Obstruction

Sudden cardiac death is an elusive process that claims a significant number of lives annually in the United States. It is often associated with increased mortality within the first year after myocardial infarction, with the highest frequency occurring among patients with left ventricular dysfunction. Therefore, increasing survival rates in patients with a history of both disorders is an important goal of therapy. Recent trials suggested that an implantable cardioverter-defibrillator (ICD) in these patients may be superior to medical intervention in reducing the high mortality rate. Four major trials measured the benefits of an ICD for patients at risk for life-threatening ventricular arrhythmias. We assessed whether patients in these trials received adequate drug therapy as directed by American College of Cardiology-American Heart Association guidelines. One aim was to determine if medicated patients who served as controls in the trials were fairly represented. Furthermore, the need for improved overall guideline adherence was apparent.

Topics: Adrenergic beta-Antagonists; Amiodarone; Angiotensin-Converting Enzyme Inhibitors; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Humans; Myocardial Infarction; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Treatment Outcome; 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: Arrhythmias, Cardiac; Cardiomyopathy, Hypertrophic, Familial; Cardiovascular Agents; Death, Sudden, Cardiac; Dyspnea; Heart Septum; Humans; Hypertrophy, Left Ventricular; Pacemaker, Artificial; Prevalence

The management of acute myocardial infarction has been revolutionized in the past decade. Advances in pharmacological and mechanical reperfusion therapy have improved the survival of patients who experience myocardial infarction. Although revascularisation techniques have been shown to reduce infarct size and in-hospital mortality, patients recovering from myocardial infarction are still at increased risk for reinfarction, congestive heart failure, and sudden death. Despite impressive technological advances, lifestyle modification and pharmacological interventions remain the key components of secondary prevention after myocardial infarction. Although the concept of secondary prevention of reinfarction and death has been investigated vigorously for several decades, preventive therapy has been seriously underused by physicians. The aim of this paper is to provide a comprehensive, evidence-based overview of secondary prevention postmyocardial infarction clinical trials, in the hope of improving the utilization of effective therapies in patients with coronary heart disease.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anticoagulants; Aspirin; Calcium Channels; Cardiovascular Agents; Clinical Trials as Topic; Coronary Circulation; Death, Sudden, Cardiac; Diet; Exercise; Heart Failure; Humans; Hypolipidemic Agents; Life Style; Myocardial Infarction; Myocardial Revascularization; Nitric Oxide Donors; Risk Factors; Secondary Prevention; Smoking Cessation; Vasodilator Agents

The clinical presentations of ischemic heart disease comprises the term of acute ischaemia syndromes, that include unstable angina pectoris, non-Q-wave myocardial infarction, Q-wave-myocardial infarction and sudden death. Among the different presentations of acute ischemic syndromes, the unstable angina and non-Q-wave myocardial infarction can be regarded together. In both pathologic entity, the plaque rupture, or erosion signifies the primary event, which is the source of the highly thrombogenic substances coming out from the core of the atherosclerotic plaque and entering to the coronary and systemic circulation. They cause a thrombocyte-rich "white" intracoronary thrombus, that is not fully obstructive, or there is adequate collateral circulation, being the pathogenetic substrate that prevents the development of transmural necrosis. The nosologically-bound two clinical entity can be called as "unstable coronary artery disease" (UCAD), since they have uniform etiologic, risk stratification and therapeutic backgrounds and also therapeutic targets that are basically distinct, they are admitted for transmural "ST-elevation" infarction. The review is discussing the therapy and the questions of follow-up of the disease according to the guidelines of the European Society of Cardiology and to the multicenter evidence based studies.

Topics: Angina, Unstable; Antithrombins; Cardiovascular Agents; Coronary Artery Bypass; Death, Sudden, Cardiac; Fibrinolytic Agents; Heart Conduction System; Heparin, Low-Molecular-Weight; Humans; Multicenter Studies as Topic; Myocardial Infarction; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Randomized Controlled Trials as Topic; Vasodilator Agents

Topics: Antihypertensive Agents; Blood Pressure; Cardiovascular Agents; Cardiovascular Diseases; Circadian Rhythm; Death, Sudden, Cardiac; Humans; Hypertension; Kidney Failure, Chronic; Myocardial Infarction

Cardiomyopathies have either a primary (without associated anomalies) or a secondary origin. They are classified in three groups according to their anatomy and function: hypertrophic, dilated or restrictive. We review here the relevant diagnostic points of each type as well as their treatment. Restrictive cardiomyopathies, arrhythmogenic right ventricle, non compaction and Uhl's anomaly will not be dealt with in detail as they are very seldom in children.

Topics: Cardiac Surgical Procedures; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Child; Death, Sudden, Cardiac; Diagnosis, Differential; Electrocardiography; Genetic Predisposition to Disease; Humans; Hypertrophy, Left Ventricular; Incidence

A cardiac localization is one of the most severe manifestations of sarcoidosis and may cause sudden death (ventricular tachycardia or atrial ventricular block III) or restrictive cardiomyopathy. Lesions are most frequently observed in the interventricular septum and the free left wall. Granulomatous infiltation can provoke nonspecific clinical, electric and echocardiographic signs, which, associated with regressive dipyridamol uptake on tomoscintigraphy, are suggestive of cardiac sarcoidosis. The diagnosis of cardiac sarcoidosis is based on the presence of systemic sarcoidosis, histological evidence of granuloma and the lack of another cause of cardiomyopathy. Corticosteroid therapy is indicated, associated with specific cardiologic treatments.

Topics: Anti-Inflammatory Agents; Biopsy; Cardiomyopathies; Cardiomyopathy, Restrictive; Cardiovascular Agents; Death, Sudden, Cardiac; Dipyridamole; Echocardiography; Electrocardiography; Heart Block; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Sarcoidosis; Steroids; Tachycardia, Ventricular; Vasodilator Agents

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

During the past 25 years, the cardiovascular effects of marine omega-3 (omega-3) fatty acids have been the subject of increasing investigation. In the late 1970s, epidemiological studies revealed that Greenland Inuits had substantially reduced rates of acute myocardial infarction compared with Western control subjects. These observations generated more than 4,500 studies to explore this and other effects of omega-3 fatty acids on human metabolism and health. From epidemiology to cell culture and animal studies to randomized controlled trials, the cardioprotective effects of omega-3 fatty acids are becoming recognized. These fatty acids, when incorporated into the diet at levels of about 1 g/d, seem to be able to stabilize myocardial membranes electrically, resulting in reduced susceptibility to ventricular dysrhythmias, thereby reducing the risk of sudden death. The recent GISSI (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico)-Prevention study of 11,324 patients showed a 45% decrease in risk of sudden cardiac death and a 20% reduction in all-cause mortality in the group taking 850 mg/d of omega-3 fatty acids. These fatty acids have potent anti-inflammatory effects and may also be antiatherogenic. Higher doses of omega-3 fatty acids can lower elevated serum triglyceride levels; 3 to 5 g/ d can reduce triglyceride levels by 30% to 50%, minimizing the risk of both coronary heart disease and acute pancreatitis. This review summarizes the emerging evidence of the use of omega-3 fatty acids in the prevention of coronary heart disease.

Topics: alpha-Linolenic Acid; Cardiovascular Agents; Coronary Disease; Death, Sudden, Cardiac; Fatty Acids, Omega-3; Fish Oils; Greenland; Humans; Inuit; Myocardial Infarction; Randomized Controlled Trials as Topic

Topics: Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Death, Sudden, Cardiac; Humans

Sudden cardiac death is characterised by the unexpected death of a patient who has been clinically stable. It is frequently due to the development of ventricular tachyarrhythmias. With appropriate treatment, patients can be appropriately resuscitated. Clinically, it is essential to develop treatment strategies to prevent such an episode, as most patients do not survive out-of-hospital cardiac arrest. beta-Blockers are an effective pharmacological therapy in patients following myocardial infarction and in those with congestive heart failure. They may also be effective in other types of heart disease. Anti-arrhythmic agents are not useful as prophylactic drug therapy for reducing mortality in patients at risk for sudden cardiac death. Amiodarone is a notable exception, which may have some benefit, particularly in some subgroups. The implantable cardioverter-defibrillator has emerged as the most effective therapy for preventing sudden cardiac death in high-risk patients. Further work is required to enhance the characterisation of high-risk patients. Genetic analyses in patients with cardiovascular disorders may also identify new approaches to the prevention of sudden cardiac death.

Topics: Adrenergic beta-Antagonists; Animals; Anti-Arrhythmia Agents; Cardiovascular Agents; Clinical Trials as Topic; Death, Sudden, Cardiac; Defibrillators, Implantable; Humans

Chronic heart failure (CHF) is generally associated with a poor prognosis with an annual mortality rate ranging between 15-50% depending on the severity of cardiac dysfunction thus presenting a major health problem in our society. Drugs for the treatment of CHF include vasodilators (ACE-inhibitors, angiotensin II receptor blockers), diuretics, digoxin and beta-blockers. However, antiarrhythmic drugs are not currently recommended in the management of CHF with the exception of beta-blockers for which a favorable effect on the prognosis could be shown. Amiodarone is effective in the suppression of ventricular arrhythmias without a significant effect on total mortality. Implanted defibrillators are superior to antiarrhythmic drug therapy in prolonging survival among survivors of sudden cardiac death. They should be offered as firstline therapy in case of life-threatening ventricular tachy-arrhythmias.

Topics: Anti-Arrhythmia Agents; Cardiovascular Agents; Chronic Disease; Death, Sudden, Cardiac; Drug Therapy, Combination; Follow-Up Studies; Heart Failure; Humans; Survival Rate; Tachycardia, Ventricular

Heart failure is a clinical syndrome that is predominantly caused by cardiovascular disorders such as coronary heart disease and hypertension. However, several classes of drugs may induce heart failure in patients without concurrent cardiovascular disease or may precipitate the occurrence of heart failure in patients with preexisting left ventricular impairment. We reviewed the literature on drug-induced heart failure, using the MEDLINE database and lateral references. Successively, we discuss the potential role in the occurrence of heart failure of cytostatics, immunomodulating drugs, antidepressants, calcium channel blocking agents, nonsteroidal anti-inflammatory drugs, antiarrhythmics, beta-adrenoceptor blocking agents, anesthetics and some miscellaneous agents. Drug-induced heart failure may play a role in only a minority of the patients presenting with heart failure. Nevertheless, drug-induced heart failure should be regarded as a potentially preventable cause of heart failure, although sometimes other priorities do not offer therapeutic alternatives (e.g., anthracycline-induced cardiomyopathy). The awareness of clinicians of potential adverse effects on cardiac performance by several classes of drugs, particularly in patients with preexisting ventricular dysfunction, may contribute to timely diagnosis and prevention of drug-induced heart failure.

Topics: Adjuvants, Immunologic; Anesthetics; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Antineoplastic Agents; Cardiovascular Agents; Death, Sudden, Cardiac; Heart Failure; Humans; Survival Rate

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

Sudden cardiac death is a major medical problem. The techniques to identify high risk patients have a limited value. Only betablockers, and perhaps amiodarone, are useful for primary prevention of sudden cardiac death. Prospective studies being carried out today with implantable cardioverter-defibrillator, will show us if these are the best way of treatment (secondary prevention) of sudden cardiac death.

Topics: Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Heart; Humans; Risk Factors

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

Ventricular arrhythmias are a frequent finding in patients with heart failure, and heart failure is a major underlying condition which is correlated to sudden death. Therefore, both sudden death and death from progression of heart failure strongly overlap. Besides long-term ECG recording, newer diagnostic techniques have been developed. The prognostic significance of the signal-averaged ECG in patients with advanced left ventricular dysfunction in the presence of coronary artery disease has been demonstrated; however, in patients with dilated cardiomyopathy, signal-averaging for detection of late potentials has not yet been clearly established as a useful diagnostic tool. Furthermore, heart period variability has been shown to correlate to overall mortality but not to a specific mechanism. Finally, programmed ventricular stimulation, though useful in patients with left ventricular dysfunction and/or heart failure in the setting of coronary artery disease, is of questionable significance in patients with dilated cardiomyopathy. With increasing degrees of left ventricular dysfunction, the efficacy of antiarrhythmic drugs decreases. On the other hand, with increasing degrees of heart failure, antiarrhythmic drugs demonstrate a greater negative inotropic effect, more frequent proarrhythmic effects, and more frequent bradyarrhythmias. Currently, several ongoing amiodarone trials are assessing different approaches of antiarrhythmic treatment in patients with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cardiovascular Agents; Clinical Trials as Topic; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Heart Failure; Humans; Risk Factors; Tachycardia, Ventricular

The pharmacologic approach to coronary protection, defined here as the prevention or delay of sudden death and myocardial infarction (without negatively affecting noncardiac mortality), is critically discussed. The value of pharmacologically treating mild hypertension and mild hypercholesterolemia is questioned, and the need for well-designed, randomized clinical trials with definitive endpoints to determine a drug's cardioprotective capability is emphasized. Based on such studies, it is concluded that some (but perhaps not all) beta-receptor antagonists as well as aspirin have been shown to protect against sudden cardiac death. Trials of thiazide diuretics, calcium antagonists, and angiotensin-converting enzyme inhibitors have not shown a reduction in sudden cardiac death, despite having individual benefits with respect to other aspects of cardiovascular disease. The demonstration that some beta blockers are cardioprotective is discussed in terms of the pathophysiology of sudden cardiac death, and differences in the pharmacokinetic profiles of individual agents.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Animals; Calcium Channel Blockers; Cardiovascular Agents; Death, Sudden, Cardiac; Europe; Humans; Hypercholesterolemia; Hypertension; Myocardial Infarction

Background Plasma omega-3 polyunsaturated fatty acids (ω3-PUFAs) have been shown to be inversely correlated with the risk of cardiovascular death in primary prevention. The risk relationship in the setting of an acute coronary syndrome is less well established. Methods and Results Baseline plasma ω3-PUFA composition (α-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) was assessed through gas chromatography with flame ionization detection in a case-cohort study involving 203 patients with cardiovascular death, 325 with myocardial infarction, 271 with ventricular tachycardia, and 161 with atrial fibrillation, and a random sample of 1612 event-free subjects as controls from MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation-Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 36), a trial of patients hospitalized with non-ST-segment-elevation -acute coronary syndrome. After inverse-probability-weighted multivariable adjustment including all traditional risk factors, a higher relative proportion of long-chain ω3-PUFAs (eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid) were associated with 18% lower odds of cardiovascular death (adjusted [adj] odds ratio [OR] per 1 SD, 0.82; 95% CI, 0.68-0.98) that was primarily driven by 27% lower odds of sudden cardiac death (adj OR per 1 SD, 0.73; 95% CI, 0.55-0.97). Long-chain ω3-PUFA levels in the top quartile were associated with 51% lower odds of cardiovascular death (adj OR 0.49; 95% CI, 0.27-0.86) and 63% lower odds of sudden cardiac death (adj OR, 0.37; 95% CI, 0.16-0.56). An attenuated relationship was seen for α-linolenic acid and subsequent odds of cardiovascular (adj OR, 0.92; 95% CI, 0.74-1.14) and sudden cardiac death (adj OR, 0.91; 95% CI, 0.67-1.25). No significant relationship was observed between any ω3-PUFAs and the odds of cardiovascular death unrelated to sudden cardiac death, myocardial infarction, atrial fibrillation, or early post-acute coronary syndrome ventricular tachycardia. Conclusions In patients after non-ST-segment-elevation-acute coronary syndrome, plasma long-chain ω3-PUFAs are inversely associated with lower odds of sudden cardiac death, independent of traditional risk factors and lipids. Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00099788.

Topics: Acute Coronary Syndrome; Biomarkers; Cardiovascular Agents; Death, Sudden, Cardiac; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Fatty Acids, Omega-3; Female; Humans; Incidence; Male; Middle Aged; Ranolazine; Risk Assessment; Risk Factors; United States

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

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

Appropriate implantable cardioverter-defibrillator (ICD) therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF) depends, in part, on the programming of tachycardia zones.. We assessed events treated with ICD shocks or antitachycardia pacing (ATP) in the Inhibition of Unnecessary RV Pacing with AV Search Hysteresis in ICDs (INTRINSIC RV) trial.. ATP and shock episodes from 1530 patients with dual-chamber ICDs were analyzed.. For episodes in which electrograms were stored and adjudicated, ATP was delivered for 763 episodes (182 patients), shock-only was delivered for 300 episodes (146 patients), and shock following ATP was delivered for 81 episodes (56 patients). ATP was delivered appropriately for 507 episodes (130 patients), with 93% success, and inappropriately for 256 episodes (89 patients). For ATP episodes, appropriate (VT: 170 ± 28 bpm) and inappropriate (not VT: 165 ± 21 bpm) rates did not differ (P = .16). When the initial therapy was shock, onset rates were higher for appropriate therapy than for inappropriate therapy (224 ± 46 bpm vs 187 ± 31 bpm; P <.001). Inappropriate ATP was more likely to be followed by a shock (odds ratio 2.49; 95% confidence interval 1.56-3.97; P <.001). Fifty-eight percent (225 of 381) of shocked episodes had rates <200 bpm. For episodes between 200 and 250 bpm, 20% (23 of 113) were polymorphic VT or VF, 59% were monomorphic VT, 19% were supraventricular, and <1% was artifact. For episodes >250 bpm, 37% were VF, 28% polymorphic VT, 23% monomorphic VT, 7% supraventricular, and 5% artifact.. In a general ICD population, ATP treated VT effectively or obviated the need for shock. Most ventricular arrhythmias <250 bpm were not VF. Proper zone programming may identify and treat VT without shock.

Topics: Aged; Cardiac Pacing, Artificial; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Electrocardiography; Equipment Failure Analysis; Health Status; Humans; Male; Middle Aged; Monitoring, Physiologic; Outcome and Process Assessment, Health Care; Tachycardia, Ventricular; Treatment Outcome

We assessed whether a novel programme to evaluate/communicate predicted coronary heart disease (CHD) risk could lower patients' predicted Framingham CHD risk vs. usual care.. The Risk Evaluation and Communication Health Outcomes and Utilization Trial was a prospective, controlled, cluster-randomised trial in nine European countries, among patients at moderate cardiovascular risk. Following baseline assessments, physicians in the intervention group calculated patients' predicted CHD risk and were instructed to advise patients according to a risk evaluation/communication programme. Usual care physicians did not calculate patients' risk and provided usual care only. The primary end-point was Framingham 10-year CHD risk at 6 months with intervention vs. usual care.. Of 1103 patients across 100 sites, 524 patients receiving intervention, and 461 receiving usual care, were analysed for efficacy. After 6 months, mean predicted risks were 12.5% with intervention, and 13.7% with usual care [odds ratio = 0.896; p = 0.001, adjusted for risk at baseline (17.2% intervention; 16.9% usual care) and other covariates]. The proportion of patients achieving both blood pressure and low-density lipoprotein cholesterol targets was significantly higher with intervention (25.4%) than usual care (14.1%; p < 0.001), and 29.3% of smokers in the intervention group quit smoking vs. 21.4% of those receiving usual care (p = 0.04).. A physician-implemented CHD risk evaluation/communication programme improved patients' modifiable risk factor profile, and lowered predicted CHD risk compared with usual care. By combining this strategy with more intensive treatment to reduce residual modifiable risk, we believe that substantial improvements in cardiovascular disease prevention could be achieved in clinical practice.

Topics: Cardiovascular Agents; Clinical Protocols; Cluster Analysis; Communication; Coronary Disease; Death, Sudden, Cardiac; Female; Humans; Male; Middle Aged; Myocardial Infarction; Prognosis; Prospective Studies; Risk Assessment; Risk Factors; Weight Loss

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

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

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

The pharmacologic approach to coronary protection, defined here as the prevention or delay of sudden death and myocardial infarction (without negatively affecting noncardiac mortality), is critically discussed. The value of pharmacologically treating mild hypertension and mild hypercholesterolemia is questioned, and the need for well-designed, randomized clinical trials with definitive endpoints to determine a drug's cardioprotective capability is emphasized. Based on such studies, it is concluded that some (but perhaps not all) beta-receptor antagonists as well as aspirin have been shown to protect against sudden cardiac death. Trials of thiazide diuretics, calcium antagonists, and angiotensin-converting enzyme inhibitors have not shown a reduction in sudden cardiac death, despite having individual benefits with respect to other aspects of cardiovascular disease. The demonstration that some beta blockers are cardioprotective is discussed in terms of the pathophysiology of sudden cardiac death, and differences in the pharmacokinetic profiles of individual agents.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Animals; Calcium Channel Blockers; Cardiovascular Agents; Death, Sudden, Cardiac; Europe; Humans; Hypercholesterolemia; Hypertension; Myocardial Infarction

Topics: Athletes; Cardiovascular Agents; Computed Tomography Angiography; Coronary Angiography; Coronary Artery Disease; Death, Sudden, Cardiac; Exercise; Humans; Predictive Value of Tests; Prognosis; Protective Factors; Risk Assessment; Risk Factors; Risk Reduction Behavior; Vascular Calcification

 The ABC (age, biomarkers, and clinical history)-stroke and ABC-bleeding are biomarker-based scores proposed to predict stroke and bleeding, but non-specificity of biomarkers is common, predicting different clinical events at the same time. We assessed the predictive performance of the ABC-stroke and ABC-bleeding scores, for outcomes beyond ischemic stroke and major bleeding, in a cohort of atrial fibrillation (AF) patients..  We included AF patients stable on vitamin K antagonists for 6 months. The ABC-stroke and ABC-bleeding were calculated and the predictive values for myocardial infarction (MI), acute heart failure (HF), a composite of cardiovascular events, and all-cause deaths were compared..  We included 1,044 patients (49.2% male; median age 76 [71-81] years). During 6.5 (4.3-7.9) years, there were 58 (5.6%) MIs, 98 (9.4%) acute HFs, 167 (16%) cardiovascular events, and 418 (40%) all-cause deaths. There were no differences in mean ABC-stroke and ABC-bleeding scores in patients with/without MI (.  In AF patients, the ABC-stroke and ABC-bleeding scores demonstrated similar predictive ability for outcomes beyond stroke and bleeding, including MI, acute HF, a composite of cardiovascular events, and all-cause deaths. This is consistent with nonspecificity of biomarkers that predict "sick" patients or poor prognosis overall.

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Area Under Curve; Atrial Fibrillation; Biomarkers; Cardiovascular Agents; Cause of Death; Comorbidity; Death, Sudden, Cardiac; Decision Support Techniques; Female; Heart Failure; Hemorrhage; Humans; Male; Mortality; Myocardial Infarction; Platelet Aggregation Inhibitors; Prognosis; ROC Curve; Severity of Illness Index; Stroke; Vitamin K

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

Topics: Cardiac Resynchronization Therapy; Cardiovascular Agents; Combined Modality Therapy; Death, Sudden, Cardiac; Disease Progression; Heart Failure; Humans; Risk Adjustment; Ventricular Remodeling

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

There is limited knowledge on the residual risk of cardiovascular death (CVD) in patients with stable coronary artery disease (CAD) who receive modern secondary prevention. Our aim was to analyze the causes of death and to determine predictors of CVD in the 5-year CORONOR registry.. We studied 4184 consecutive CAD outpatients who were free from any myocardial infarction (MI) or coronary revascularization for more than 1 year at inclusion. Antithrombotics were prescribed in 99%, statins in 92%, inhibitors of renin-angiotensin system in 82%, and β-blockers in 79%; 86% had prior coronary revascularization. Follow-up was performed at 5 years with adjudication of the causes of death.. There were 677 deaths during follow-up. The cause of death was cardiovascular in 269 patients (1.3%/year), with 99 deaths from heart failure (HF), 91 sudden deaths, and 65 vascular deaths (stroke, MI, limb or mesenteric ischemia, aortic aneurysm). Predictors of CVD were age [subhazard ratio (SHR)=1.06 (1.04-1.07) per year increase], previous hospitalization for decompensated HF [SHR=3.10 (2.19-4.40)], left ventricular ejection fraction [SHR=0.97 (0.96-0.98) per percentage increase], prior aortic or peripheral intervention [SHR=1.61 (1.12-2.13)], and estimated glomerular filtration rate [SHR=0.99 (0.98-1.00)] per ml/min/1.73m increase]. In analyses stratified on age, prior HF, and left ventricular ejection fraction, the estimated 5-year cardiovascular mortality rates varied from less than 2% to more than 50%.. In stable CAD patients widely treated by secondary prevention medications, the main causes of CVD are death from HF and sudden death. The risk of CVD can be predicted by simple baseline variables. New therapeutic strategies are needed for the high-risk patients.

Topics: Aged; Cardiovascular Agents; Cause of Death; Coronary Artery Disease; Death, Sudden, Cardiac; Female; France; Heart Failure; Humans; Incidence; Male; Middle Aged; Myocardial Revascularization; Registries; Risk Assessment; Risk Factors; Secondary Prevention; Stroke Volume; Time Factors; Treatment Outcome; Ventricular Function, Left

Early repolarization syndrome (ERS) is associated with polymorphic ventricular tachycardia (PVT) and ventricular fibrillation, leading to sudden cardiac death.. The present study tests the hypothesis that the transient outward potassium current (Ito)-blocking effect of phosphodiesterase-3 (PDE-3) inhibitors plays a role in reversing repolarization heterogeneities responsible for arrhythmogenesis in experimental models of ERS.. Transmembrane action potentials (APs) were simultaneously recorded from epicardial and endocardial regions of coronary-perfused canine left ventricular (LV) wedge preparations, together with a transmural pseudo-electrocardiogram. The Ito agonist NS5806 (7-15 μM) and L-type calcium current (ICa) blocker verapamil (2-3 μM) were used to induce an early repolarization pattern and PVT.. After stable induction of arrhythmogenesis, the PDE-3 inhibitors cilostazol and milrinone or isoproterenol were added to the coronary perfusate. All were effective in restoring the AP dome in the LV epicardium, thus abolishing the repolarization defects responsible for phase 2 reentry and PVT. Arrhythmic activity was suppressed in 7 of 8 preparations by cilostazol (10 μM), 6 of 7 by milrinone (2.5 μM), and 7 of 8 by isoproterenol (0.1-1 μM). Using voltage clamp techniques applied to LV epicardial myocytes, both cilostazol (10 μM) and milrinone (2.5 μM) were found to reduce Ito by 44.4% and 40.4%, respectively, in addition to their known effects to augment ICa.. Our findings suggest that PDE-3 inhibitors exert an ameliorative effect in the setting of ERS by producing an inward shift in the balance of current during the early phases of the epicardial AP via inhibition of Ito as well as augmentation of ICa, thus reversing the repolarization defects underlying the development of phase 2 reentry and ventricular tachycardia/ventricular fibrillation.

Topics: Action Potentials; Animals; Cardiac Electrophysiology; Cardiovascular Agents; Cilostazol; Death, Sudden, Cardiac; Disease Models, Animal; Dogs; Electrocardiography; Ion Channels; Isoproterenol; Milrinone; Tachycardia, Ventricular; Tetrazoles; Ventricular Fibrillation

Topics: Acute Disease; Adrenergic beta-Antagonists; Algorithms; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Biphenyl Compounds; Cardiac Resynchronization Therapy; Cardiovascular Agents; Chronic Disease; Death, Sudden, Cardiac; Defibrillators, Implantable; Drug Combinations; Early Medical Intervention; Echocardiography; Europe; Extracorporeal Membrane Oxygenation; Heart Failure; Humans; Ivabradine; Mineralocorticoid Receptor Antagonists; Natriuretic Peptides; Practice Guidelines as Topic; Spain; Stroke Volume; Tetrazoles; Valsartan

Studies evaluating long-term (≥5 years) outcome of percutaneous coronary intervention (PCI) compared with coronary artery bypass grafting (CABG) in patients with unprotected left main coronary artery disease (ULMCAD) are still limited, despite concerns for late adverse events after drug-eluting stents implantation.. We identified 1,004 patients with ULMCAD (PCI: n=364, CABG: n=640) among 15,939 patients with first coronary revascularization enrolled in the CREDO-Kyoto PCI/CABG registry cohort-2. The primary outcome measure in the current analysis was a composite of death, myocardial infarction, and stroke (death/MI/stroke). The cumulative 5-year incidence of and the adjusted risk for death/MI/stroke were significantly higher in the PCI group than in the CABG group (34.5% vs. 24.1%, log-rank P<0.001, adjusted hazard ratio (HR): 1.48 [95% confidence interval (CI): 1.07-2.05, P=0.02]). The adjusted risks for all-cause death was not significantly different between the 2 groups. Regarding the stratified analysis by the SYNTAX score, the adjusted risk for death/MI/stroke was not significantly different between the 2 groups in patients with low (<23) or intermediate (23-33) SYNTAX score, whereas it was significantly higher in the PCI group than in the CABG group in patients with high (≤33) SYNTAX score.. CABG as compared with PCI was associated with better long-term outcome in patients with ULMCAD, especially those with high anatomical complexity.

Topics: Cardiovascular Agents; Cause of Death; Combined Modality Therapy; Comorbidity; Coronary Artery Bypass; Coronary Disease; Death, Sudden, Cardiac; Follow-Up Studies; Humans; Japan; Kaplan-Meier Estimate; Mortality; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proportional Hazards Models; Registries; Risk; Severity of Illness Index; Stents; Stroke; Treatment Outcome

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

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

Peripartum cardiomyopathy is a life-threatening cardiac condition affecting pregnant women either late in pregnancy or early in the post-partum period. The latest studies show a dramatic improvement in the mortality rates of women affected with this disorder, which has been correlated with advances in medical therapy for heart failure. However, patients continue to die of this condition. The following case report describes a typical patient with peripartum cardiomyopathy diagnosed on clinical grounds, along with echocardiogram findings of severe systolic dysfunction and global hypokinesis consistent with dilated cardiomyopathy. Emergency cesarean delivery had to be performed for fetal distress. There was significant improvement of the patient's condition with standard pharmacological management for heart failure at the time of discharge. However, five weeks after discharge, fatal cardiac arrest occurred. It is hoped that this article will raise awareness about this rare but potentially fatal condition and promote understanding of its main clinical features, diagnostic criteria, and conventional pharmacological management.

Topics: Adult; Cardiomyopathies; Cardiovascular Agents; Cesarean Section; Death, Sudden, Cardiac; Emergency Treatment; Fatal Outcome; Female; Humans; Peripartum Period

Topics: Cardiac Surgical Procedures; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Exercise Test; Genetic Predisposition to Disease; Genetic Testing; Heredity; Humans; Magnetic Resonance Imaging; Mutation; Pedigree; Phenotype; Predictive Value of Tests; Primary Prevention; Risk Assessment; Risk Factors; Risk Reduction Behavior; Ventricular Outflow Obstruction

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

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

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

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

Clinical utility of QTc prolongation as a predictor for sudden cardiac death (SCD) has not been definitely established. Ranolazine causes modest QTc prolongation, yet it shows antiarrhythmic properties. We aimed to determine the association between prolonged QTc and risk of SCD, and the effect of ranolazine on this relationship.. The relationship between baseline QTc and SCD was studied in 6492 patients with non-ST elevation acute coronary syndrome (NSTEACS) randomized to placebo or ranolazine in the MERLIN-TIMI 36 trial. In the placebo group, an abnormal QTc interval (≥450 ms in men, ≥470 ms in women) was associated with a two-fold increased risk of SCD (hazard ratio, HR, 2.3, P = 0.005) after adjustment for other risk factors (age ≥75 years, NYHA class III/IV, high TIMI risk score, ventricular tachycardia ≥8 beats, digitalis, and antiarrhythmics). In the ranolazine group, the association between abnormal QTc and SCD was similar to placebo, but not significant (HR 1.8, P = 0.074). There was no significant difference between placebo and ranolazine in the risk for SCD in patients with abnormal QTc (HR 0.78, P = 0.48). When QTc was used as a continuous variable, for every 10 ms increase in QTc, hazard rate for SCD increased significantly by 8% (P = 0.007) in the placebo group, and only by 2.9% (P = 0.412; P for interaction=0.25) in the ranolazine group.. In NSTEACS patients treated with placebo, prolonged QTc was a significant independent predictor for SCD. Ranolazine, compared with placebo, was not associated with increased risk for SCD in patients with prolonged QTc.

Topics: Acetanilides; Acute Coronary Syndrome; Aged; Cardiovascular Agents; Death, Sudden, Cardiac; Electrocardiography; Female; Humans; Incidence; Kaplan-Meier Estimate; Long QT Syndrome; Male; Multivariate Analysis; Piperazines; Proportional Hazards Models; Randomized Controlled Trials as Topic; Ranolazine; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

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

Following national guidance on management of sudden unexplained death (SUD) in the young, inherited cardiac conditions (ICC) clinics were established to identify and treat relatives thought to be at increased risk. Studies have examined diagnostic yield of these clinics but outcome of clinical management has not been reported.. Observational outcome study of consecutively referred relatives of SUD victims.. Regional ICC clinic.. 193 individuals (108 families) referred to a regional ICC clinic following SUD/aborted cardiac arrest of a young relative (mean follow-up 16.5 months, range 0.1-61).. All individuals underwent assessment by history, examination, ECG and echocardiography. Exercise electrocardiography, ajmaline provocation, further imaging techniques and genetic testing were performed in selected individuals. Implantable cardioverter-defibrillator (ICD) insertion based on national guidelines.. Forty-five patients (23%) from 38 families (35%) were diagnosed with an inheritable cause of sudden death. Eighteen had potentially prognostically important medication commenced and 4 had an ICD inserted on clinic recommendation (2 hypertrophic cardiomyopathy, 1 dilated cardiomyopathy, 1 arrhythmogenic right ventricular cardiomyopathy). Two other individuals had ICDs removed after negative testing for familial RYR2 mutations. No deaths have occurred during follow-up to date.. A diagnosis of an inheritable cause of sudden death was obtained in a significant minority of those with a family history of SUD/aborted cardiac arrest. The number of ICDs inserted as a result of specialist assessment was very small (2%). A major function of the clinic is reassurance of the clinically normal and cessation of treatment after exclusion of familial disease by genetic testing.

Topics: Adult; Algorithms; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Exercise Test; Female; Genetic Testing; Heart Arrest; Heart Defects, Congenital; Humans; Male; Middle Aged; Pedigree; Prognosis; Young Adult

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

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

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

We examined the potential of oral administration of nicorandil for protecting against cardiac death in hemodialysis patients without obstructive coronary artery disease.. This study was based on a cohort study of 155 hemodialysis patients with angiographic absence of obstructive coronary lesions, with analysis performed in 100 propensity-matched patients (54 men and 46 women, 64 ± 10 years), including 50 who received oral administration of nicorandil (15 mg/day, nicorandil group) and 50 who did not (control). The efficacy of nicorandil in preventing cardiac death was investigated.. Over a mean follow-up period of 5.3 ± 1.9 years, we observed 25 cardiac deaths among 100 propensity-matched patients, including 6 due to acute myocardial infarction, 11 due to heart failure, and 8 due to sudden cardiac death. The incidence of cardiac death was lower (p < 0.001) in the nicorandil group (4/50, 8%) than in the control (21/50, 42%). On multivariate Cox hazard analysis, cardiac death was inversely associated with oral nicorandil (hazard ratio, 0.123; p = 0.0002). On Kaplan-Meier analysis, cardiac death-free survival rates at 5 years were higher in the nicorandil group than in the control group (91.4 vs. 66.4%).. Oral nicorandil may inhibit cardiac death of hemodialysis patients without obstructive coronary artery disease.

Topics: Administration, Oral; Aged; Cardiovascular Agents; Coronary Angiography; Coronary Disease; Death, Sudden, Cardiac; Drug Evaluation; Female; Follow-Up Studies; Heart Failure; Humans; Insulin Resistance; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Nicorandil; Proportional Hazards Models; Renal Dialysis; Retrospective Studies; Tomography, Emission-Computed, Single-Photon

Topics: Aged; Angina Pectoris, Variant; Cardiovascular Agents; Coronary Angiography; Death, Sudden, Cardiac; Electrocardiography, Ambulatory; Humans; Male; Methylergonovine; Predictive Value of Tests; Resuscitation; Telemetry; Time Factors; Treatment Outcome

Topics: Adult; Antigens, Viral; Capsid; Cardiopulmonary Resuscitation; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Electrocardiography; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Immunoglobulin G; Immunoglobulin M; Myocarditis; Shock, Cardiogenic; Ventricular Fibrillation

Topics: Cardiovascular Agents; Coronary Artery Disease; Death, Sudden, Cardiac; Defibrillators, Implantable; Female; Humans; Male; Needs Assessment; Prognosis

Topics: Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Death, Sudden, Cardiac; Genetic Predisposition to Disease; Humans; Phenotype; Recovery of Function; Risk Factors; Treatment Outcome

Electrocardiographic ventricular repolarization QT parameters are independent risk factors for cardiovascular events and sudden cardiac death in diabetic patients. The aim of the study was to investigate the association of polymorphisms of the nitric oxide synthase 1 adaptor protein (NOS1AP) gene with QT interval in Chinese subjects with or without Type 2 diabetes.. Three single nucleotide polymorphisms (SNPs) (rs10494366, rs12143842 and rs12029454) were genotyped in 1240 Type 2 diabetic patients (631 men and 609 women) and 1196 normal controls (433 men and 763 women). Individuals with overt diseases other than diabetes were excluded. Heart-rate corrected QT interval (QTc) was determined by standard 12-lead ECG and Bazett formula. Sex-pooled analysis and sex-specific analysis for genotype-phenotype association were both conducted.. In the diabetic group, the rs12143842 T allele was associated with a 3.87-ms (P = 0.014, empirical P = 0.039) increase in QTc duration for each additional allele copy, while rs10494366 and rs12029454 exhibited no significant association with QTc. We found no evidence of association for the three SNPs in subjects with normal glucose regulation. No significant SNP-gender and -diabetes affection interaction was observed.. The genetic variant rs12143842 in NOS1AP is associated with QT interval duration in a Chinese population with Type 2 diabetes. Future studies in different populations are needed to validate this finding and to evaluate the impact of NOS1AP variants on cardiovascular events and sudden cardiac death in diabetic patients.

Topics: Adaptor Proteins, Signal Transducing; Asian People; Cardiovascular Agents; Death, Sudden, Cardiac; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Genetic Variation; Genotype; Humans; Long QT Syndrome; Male; Middle Aged; Myocardial Infarction; Phenotype; Polymorphism, Single Nucleotide; Risk Factors

Topics: Benzazepines; Cardiovascular Agents; Death, Sudden, Cardiac; Heart Failure; Heart Rate; Humans; Ivabradine; Life Expectancy; Randomized Controlled Trials as Topic

Topics: Atrial Fibrillation; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Death, Sudden, Cardiac; Genetic Predisposition to Disease; Humans; Magnetic Resonance Imaging

A 60-year-old man who had serious chest and arm pain died suddenly during hospitalization. He suffered from coronary vasospastic angina complicated by a fatal acute fulminant-type of myocarditis associated with Churg-Strauss syndrome (CSS). The diagnosis at autopsy was acute progressive eosinophilic myocarditis associated with CSS.

Topics: Angina Pectoris; Autopsy; Cardiovascular Agents; Churg-Strauss Syndrome; Coronary Angiography; Coronary Vasospasm; Death, Sudden, Cardiac; Electrocardiography; Eosinophilia; Fatal Outcome; Humans; Male; Middle Aged; Myocarditis

Topics: Angioplasty, Balloon, Coronary; Anticholesteremic Agents; Azetidines; Cardiovascular Agents; Combined Modality Therapy; Coronary Disease; Coronary Stenosis; Death, Sudden, Cardiac; Ezetimibe; Humans; Kaplan-Meier Estimate; Life Style; Multicenter Studies as Topic; Myocardial Infarction; Outcome and Process Assessment, Health Care; Randomized Controlled Trials as Topic; Simvastatin

Topics: Cardiovascular Agents; Death, Sudden, Cardiac; Diabetes Mellitus, Type 2; Humans; Hyperkalemia; Hypertension; Hypertrophy, Left Ventricular; Hypoglycemic Agents; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Risk Factors; Sulfonylurea Compounds

QT prolongation is an important risk factor for sudden cardiac death. About 35% of QT-interval variation is heritable. In a recent genome-wide association study, a common variant (rs10494366) in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene was found to be associated with QT-interval variation. We tested for association of 2 NOS1AP variants with QT duration and sudden cardiac death.. The Rotterdam Study is a population-based, prospective cohort study of individuals > or = 55 years of age. The NOS1AP variants rs10494366 T>G and rs10918594 C>G were genotyped in 6571 individuals. Heart rate-corrected QT interval (QTc) was determined with ECG analysis software on up to 3 digital ECGs per individual (total, 11,108 ECGs from 5374 individuals). The association with QTc duration was estimated with repeated-measures analyses, and the association with sudden cardiac death was estimated by Cox proportional-hazards analyses. The rs10494366 G allele (36% frequency) was associated with a 3.8-ms (95% confidence interval, 3.0 to 4.6; P=7.8x10(-20)) increase in QTc interval duration for each additional allele copy, and the rs10918594 G allele (31% frequency) was associated with a 3.6-ms (95% confidence interval, 2.7 to 4.4; P=6.9x10(-17)) increase per additional allele copy. None of the inferred NOS1AP haplotypes showed a stronger effect than the individual single-nucleotide polymorphisms. There were 233 sudden cardiac deaths over 11.9 median years of follow-up. No significant association was observed with sudden cardiac death risk.. Common variants in NOS1AP are strongly associated with QT-interval duration in an elderly population. Larger sample sizes are needed to confirm or exclude an effect on sudden cardiac death risk.

Topics: Adaptor Proteins, Signal Transducing; Aged; Aged, 80 and over; Alleles; Cardiovascular Agents; Cohort Studies; Death, Sudden, Cardiac; Electrocardiography; Female; Follow-Up Studies; Genotype; Haplotypes; Humans; Long QT Syndrome; Male; Middle Aged; Netherlands; Phenotype; Polymorphism, Single Nucleotide; Proportional Hazards Models; Prospective Studies; Risk Factors; Suburban Population

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

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

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

The choice of optimal therapy in a patient with borderline coronary lesion is difficult. The long-term outcome of conservatively treated patients has not yet been well defined.. To analyse long-term outcome in patients with a borderline lesion in a single coronary artery who were selected for conservative treatment.. The study group consisted of 65 patients (mean age 59.4+/-7.4 years, 48 males) with (1) stable angina (CCS class I/II), (2) isolated single borderline coronary lesion (40-70% stenosis demonstrated by quantitative coronary angiography) and (3) no demonstrable ischaemia during non-invasive tests. Patients with heart failure, left ventricular ejection fraction <50% or acute coronary syndrome within 6 months preceding the study were not included. All patients were prescribed statins, angiotensin converting enzyme inhibitors and aspirin. Follow-up end-points included cardiac death, new myocardial infarction (MI) with or without ST segment elevation and revascularisation of the target coronary artery.. The follow-up duration was 18.4+/-8.5 months (range 12-33, median 18 months). Forty nine (75%) patients remained free from angina during daily activity. Coronary events occurred in 16 (25%) patients, including three (5%) serious complications -- sudden death, new MI with ST elevation and new MI without ST elevation. The remaining 13 (20%) patients underwent percutaneous revascularisation of the target coronary artery. Coronary angiography was repeated in 16 (25%) patients. When the patients were divided into two groups according to the follow-up results (with or without coronary event), no differences in the clinical characteristics, lesion localisation and length or degree of stenosis were noted.. (1) Conservatively treated patients with stable angina and borderline coronary stenosis have a high rate of coronary events, especially revascularisation, during a long-term follow-up. (2) Clinical parameters and quantitative coronary angiography do not identify those patients with borderline coronary lesions who are at increased risk of future coronary events.

Topics: Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Cardiovascular Agents; Coronary Angiography; Coronary Disease; Coronary Stenosis; Death, Sudden, Cardiac; Female; Heart Conduction System; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Time Factors; Treatment Outcome

Left ventricular ejection fraction (LVEF) predicts device discharges in patients with implantable cardioverter-defibrillators (ICDs). The relationship between severity of congestive heart failure (CHF) and ICD discharges is less clear.. We prospectively analyzed the association between CHF and risk of appropriate ICD discharges in the Triggers Of Ventricular Arrhythmias (TOVA) study, a cohort study of ICD patients conducted at 31 centers in the United States. Reported shocks were confirmed for sustained ventricular tachycardia (VT) or fibrillation (VF) by analysis of stored electrograms. Proportional hazards models included CHF categorized by New York Heart Association class. Baseline CHF was present among 502 (44%) of 1140 patients; 170 (34%) had class I, 230 (46%) had class II, 97 (19%) had class III, and only 5 (1%) had class IV symptoms. During median follow-up of 212 days, 92 patients experienced 1 or more appropriate ICD discharges. Class III CHF was associated in a statistically significantly manner with ICD discharge for VT/VF (hazard ratio 2.40, 95% CI 1.16 to 4.98), even with adjustment for LVEF. The combination of LVEF <0.20 and class III symptoms resulted in a particularly high risk of shocks for VT/VF (hazard ratio 3.90, 95% CI 1.28 to 11.92).. Class III CHF, an easily accessible clinical measure, is an independent risk factor, along with LVEF, for ventricular arrhythmias that require shock therapy among ICD patients. Whether patients with class III CHF benefit to a greater degree from ICDs and whether aggressive treatment of CHF in ICD patients may prevent ventricular arrhythmias remains to be determined.

Topics: Actuarial Analysis; Aged; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Disease-Free Survival; Electric Countershock; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk; Risk Factors; Severity of Illness Index; Stroke Volume; Tachycardia, Ventricular; United States; Ventricular Fibrillation

Despite the epidemiological importance of coronary artery disease, cardiovascular events are rare from the individual viewpoint. There is considerable uncertainty when to start medical treatment. A given risk factor modification results in a relative risk reduction independent of the global risk. Therefore the global risk determines the absolute benefit of a preventive measure. The global risk can be estimated using different scoring systems. Using the global risk and the expected relative risk reduction, the Number Needed to Treat (NNT) to avoid one event or cardiac death can be calculated. The NNT is a measure for the usefulness of a preventive intervention. A NNT of < 200 appears acceptable for primary prevention. This can be achieved with pharmacological preventive strategies if the global risk of 10 years is > or = 20%. As age is one of the most important risk predictors the need for treatment at comparable risk factor constellations is age dependent. Risk stratification with estimation of the NNT is therefore important for the decision to treat or not to treat.

Topics: Adult; Aged; Cardiovascular Agents; Cholesterol, HDL; Cholesterol, LDL; Coronary Disease; Cross-Sectional Studies; Death, Sudden, Cardiac; Diabetes Complications; Diabetes Mellitus; Female; Germany; Humans; Hypercholesterolemia; Hypertension; Male; Mass Screening; Middle Aged; Risk Assessment; Triglycerides

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 new ESC guidelines for secondary prevention after STEMI recommend acetylsalicylic acid, betablockers, ACE inhibitors, statins and as a new therapeutic option 1 g n-3-fatty acids. They also advocate strict control of elevated blood pressure and plasma glucose level. To stop smoking remains obligatory, supplemented by the advice to adhere to a mediterranean diet. The clinical value of using 1 g n-3-fatty acids was shown in the GISSI-P trial and seem to reduce especially arrhythmic events. Considering the number needed to treat for the different pharmacologic therapies, betablockers and ACE inhibitors are essentials if not contraindicated, n-3-fatty acids and statins show each comparable efficacy while acetylsalicylic acid still provides a good cost/benefit relation due to its low price.

Topics: Cardiovascular Agents; Clinical Trials as Topic; Combined Modality Therapy; Death, Sudden, Cardiac; Diet, Mediterranean; Fatty Acids, Omega-3; Humans; Myocardial Infarction; Practice Guidelines as Topic; Risk Factors; Secondary Prevention; Survival Rate; Treatment Outcome

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: Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Humans; Physician Assistants; Practice Guidelines as Topic

Topics: Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Combined Modality Therapy; Death, Sudden, Cardiac; Defibrillators, Implantable; Heart Septum; Humans; Minimally Invasive Surgical Procedures; Pacemaker, Artificial; Survival Rate; Ventricular Outflow Obstruction

Topics: Acid-Base Imbalance; Cardiovascular Agents; Cardiovascular Diseases; Death, Sudden, Cardiac; Electrolytes; Humans; Survival Analysis; United States; Water-Electrolyte Imbalance

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

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

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

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