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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this review, a brief overview of the different arrhythmogenic mechanisms is given, emphasizing that the mechanisms for initiation and maintenance of tachyarrhythmias are often not the same. Normal automaticity in Purkinje fibers, surrounded by partially depolarized tissue providing entrance block, is most likely responsible for ventricular premature beats and enhanced automaticity can lead to (rare) cathecholamine dependent ventricular tachycardias. Abnormal automaticity in partially depolarized cells may underlie ectopic atrial tachycardias and accelerated idioventricular rhythms in the subacute phase of myocardial infarction. Triggered activity based on early afterdepolarizations may trigger torsade de pointes in both the congenital and acquired long QT syndrome. The various mutations, affecting both potassium and sodium channels, will be discussed. Cellular calcium overload, which may occur in digitalis intoxication, hypertrophy and heart failure, is the cause for delayed afterdepolarizations and triggered activity. Reentry, anatomical and functional, ordered or reentry, is by far the most common cause of both atrial and ventricular tachycardias and fibrillation. Special attention will be given to the phenomenon of "electrical remodeling" in which prolonged episodes of rapid electrical activity leads to changes in ion channel function, which in their turn cause long lasting electrophysiological alterations.
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PMID:Electrophysiology of arrhythmias. 1032 53

Sudden cardiac death due to ventricular arrhythmias remains a significant problem. In most studies about 50% of all death related to coronary artery disease and heart failure are sudden and unexpected and are caused by acute fatal ventricular tachycardia and fibrillation. Most of the patients suffering sudden cardiac death have some kind of structural heart disease but 80% of SCD events are associated with coronary artery disease, 10-15% with dilated and hypertrophic cardiomyopathy, and only small fraction with the less common disorders as valvular heart disease, ventricular dysplasia and cardiac involvement in sarcoidosis or amyloidosis. In some patients the anomaly responsible for sudden cardiac death is not structural but mainly electrical as in patients with the long QT syndrome, WPW syndrome or in patients with a proarrhythmic effect from antiarrhythmic drugs. In this review, data from clinical trials and other studies on on antiarrhythmic therapies have been evaluated in order to determine effective strategies for the prevention sudden cardiac death in high risk patients. Taken together with the mortality data routine prophylactic use of class I antiarrhythmic drugs in the patients survivors of acute myocardial infarction and patients with heart failure is associated with increased risk of death. Conversely beta-blockers are associated with significant reduction in nonfatal cardiac arrest in the short term trials and sudden cardiac death in long term trials. These benefits are likely due to relief ischemia, reduction of heart rate and maintenance favourable autonomic nervous system balance. Overall trial data on amiodarone suggests that this agent is effective in reducing the risk of death in survivors of cardiac arrest, post infarction patients, and patients with heart failure but the routine prophylactic use of amiodarone remains of uncertain efficacy. The physician who considers the use of antiarrhythmic medications in patients with ventricular arrhythmias must be aware of which arrhythmias are malignant or potentially malignant and which are benign and the decision to initiate antiarrhythmic therapy should be based on consideration of the patients absolute mortality risk.
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PMID:[Antiarrhythmic agents in the prevention of sudden cardiac death]. 1036 92

SCD continues to be an important cause of death and morbidity. Despite expanding insight into the mechanisms causing SCD, the population at high risk is not being effectively identified. Although there is still much to do in the management phase of SCD (predicting the efficacy of various therapies), recent clinical trials have helped define the relative risks and benefits of therapies in preventing SCD. Trials are underway to determine whether treating other patient populations, including asymptomatic patients after MI, will improve survival rate. The approach to reducing mortality rate will always be multifaceted; primary prevention of coronary artery disease and prompt salvage of jeopardized myocardium are 2 important aspects of this approach. In addition to interventions for MI, such as myocardial revascularization when indicated, simple and easily administered therapies that are likely to remain the most effective prophylactic interventions are aspirin, ACE inhibitors, beta-blockers, and cholesterol-lowering agents. However, the MADIT and AVID data clearly demonstrate a role for ICD therapy in a subgroup of patients who have VT/VF and are at risk of cardiac arrest. Even though the absolute magnitude of benefit associated with ICDs is still to be determined, the AVID study and other recent reports provide convincing evidence that patients who have VT/VF fare better with ICDs than with antiarrhythmic drug therapy. For the high-risk population described in this article, in addition to aggressive anti-ischemic and heart failure therapy, ICDs are now a mainstay of life-saving treatment. Still to be surmounted is the challenge of identifying patients who have nonischemic substrates and of providing them with the appropriate therapy. Guided by genetic studies and new insight into the mechanisms of such problems as congenital long QT syndrome, life-saving and life-enhancing therapies may soon be available for the management of SCD.
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PMID:Sudden cardiac death. 1045 74

Heart failure often is complicated by lethal arrhythmias. This article presents an overview of current thinking about the mechanisms of sudden death in heart failure, with an emphasis on the hypothesis that cardiomyopathy is an acquired form of the long QT syndrome.
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PMID:Heart failure: the electrophysiologic connection. 1051 68

The inherited long QT syndrome (LQTS) is a familial disease characterized by QT interval changes that often are labile, syncope, and sudden death due to arrhythmias, predominantly in young people. Multiple mutations in five genes encoding structural subunits of cardiac ion channels now have been identified in families with LQTS. Correlations are being described between genotype and specific clinical features in LQTS. However, increasing screening of affected families and sporadic cases has identified incomplete penetrance with highly variable clinical manifestations, even among individuals carrying the same mutations. The identification of LQTS disease genes represents a crucial first step in developing an understanding of the molecular basis for normal cardiac repolarization. This information will be important not only for identifying new therapies in LQTS, but also in further understanding arrhythmias, and their potential therapies, in situations such as heart failure, cardiac hypertrophy, myocardial infarction, or sudden infant death syndrome, where abnormal repolarization has been linked to sudden death. LQTS thus presents a new paradigm to cardiac electrophysiology, in which new molecular information is being brought to bear both on clinical management of patients and on development of a new framework to study the fundamental causes of arrhythmias and new approaches to therapy.
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PMID:Inherited long QT syndromes: a paradigm for understanding arrhythmogenesis. 1063 97

Heart failure leads to marked suppression of the Ca(2+)-independent transient outward current (I(to1)), but it is not clear whether I(to1) downregulation suffices to explain the concomitant action potential prolongation. To investigate the role of I(to1) in cardiac repolarization while circumventing culture-related action potential alterations, we injected adenovirus vectors in vivo to overexpress or to suppress I(to1) in guinea pigs and rats, respectively. Myocytes were isolated 72 hours after intramyocardial injection and stimulation of the ecdysone-inducible vectors with intraperitoneal injection of an ecdysone analog. Kv4.3-infected guinea pig myocytes exhibited robust transient outward currents. Increasing density of I(to1) progressively depressed the plateau potential in Kv4. 3-infected guinea pig myocytes and abbreviated action potential duration (APD). In vivo infection with a dominant-negative Kv4. 3-W362F construct suppressed peak I(to1) in rat ventriculocytes, elevated the plateau height, significantly prolonged the APD, and resulted in a prolongation by about 30% of the QT interval in surface electrocardiogram recordings. These results indicate that I(to1) plays a crucial role in setting the plateau potential and overall APD, supporting a causative role for suppression of this current in the electrophysiological alterations of heart failure. The electrocardiographic findings indicate that somatic gene transfer can be used to create gene-specific animal models of the long QT syndrome.
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PMID:Molecular dissection of cardiac repolarization by in vivo Kv4.3 gene transfer. 1077 52

The role of genetics in heart disease diagnosis and management is expanding daily. Clear genetic components have been found for diseases such as hypertrophic cardiomyopathy, heart failure, and coronary artery disease. Rhythm disturbances with genetic components are atrial fibrillation and long QT syndrome. Gene therapies to treat cardiac diseases include those designed to prevent vein graft stenosis and those that promote coronary angiogenesis.
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PMID:The evolving role of genetics in the diagnosis and management of heart disease. 1107 81

QT dispersion reflects in homogenecity of ventricular repolarization. It is calculated using 12-leads standard synchronized ECG or 24-hours Holter monitoring. The most common used indicators are: QT dispersion (QTd), based on Bazett's formula corrected for heart rate QT dispersion (QTcd) and QT dispersion ratio (QTdR). QT apex and QTd corrected for total number of leads ECG in which QT interval was counted are rare used. Increased QT dispersion is observed among others: following myocardial infarction (MI), coronary heart disease (CAD), hypertension, chronic heart failure (CHF), long QT syndrome, as well as diabetes. Following mentioned diseases increased QT dispersion has prognostic value for sustained ventricular tachycardia. Dispersion of repolarization > or = 80 ms after MI is a risk factor for sudden cardiac death. Following acute MI decrease of QT dispersion after successful thrombolytic therapy is observed and its value > or = 100 ms is regarded as a marker of reperfusion insufficiency. QT dispersion in patients with CAD correlates with extent of ischemia and decreases after coronary angioplasty (PTCA). In recent years beneficial effect of angiotensin-converting enzyme inhibitors and beta-adrenolytic therapy on QT dispersion was described. Actually the improvement of computerised methods in assessment of QT dispersion is observed, but it require further investigations.
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PMID:[Measurement dispersion of the QT interval and its significance in different diseases]. 1157 33

Recent studies have established the presence of three distinct cell types in the ventricular myocardium: epicardial, M and endocardial cells. Epicardial and M cell action potentials differ from endocardial cells with respect to the morphology of phase 1. These cells possess a prominent transient outward current (I(to))-mediated notch responsible for the 'spike and dome' morphology of the epicardial and M cell response. M cells are distinguished from the other cell types in that they display a smaller slowly activating delayed rectifier current (I(Ks)), but a larger late sodium current (late I(Na)) and sodium-calcium exchange current (I(Na-Ca)). These ionic distinctions underlie the longer action potential duration (APD) and steeper APD-rate relationship of the M cell, which is more pronounced in the presence of antiarrhythmic agents with class III actions. The preferential prolongation of the M cell action potential results in the development of a transmural dispersion of repolarization (TDR), which can be estimated from the electrocardiogram (ECG) as the interval between the peak and the end of the T wave (QTpeak-QTend interval). Using the canine arterially perfused ventricular wedge model, transmembrane action potentials of the various cardiac cell types can be correlated to the waveforms of the ECG, providing insight into the cellular etiology of ECG abnormalities. Two congenital syndromes of sudden cardiac death that have been modeled using this technique are the long QT and Brugada syndromes. The long QT syndrome has been linked to 5 gene mutations on chromosomes 3, 7, 11, and 21. Mutations in the cardiac sodium channel SCN5A have been linked to families with a history of the Brugada syndrome. Although the etiologies of these two syndromes are different, lethal arrhythmias in both are thought to arise due to amplification of intrinsic electrical heterogeneities. Similar mechanisms are likely responsible for life-threatening arrhythmias in a variety of other cardiomyopathies ranging from heart failure and hypertrophy, which involve mechanisms similar to those operative in LQTS, to ischemia and infarction, which may involve mechanisms more closely resembling those responsible for the Brugada syndrome.
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PMID:Electrical heterogeneity within the ventricular wall. 1177 69

In the United States alone 300,000-400,000 people die of sudden cardiac death every year. Much of this mortality is assumed to be caused by ventricular tachyarrhythmias. Prolonged QTc reflect cardiac repolarization prolongation and/or increased repolarization inhomogenity known to be associated with increased risk of arrhythmias. The paper gives a review of the possibilities to assess the risk of ventricular arrhythmia and/or cardiac death from QTc. Prolonged QTc may hold independent prognostic importance for mortality in common diseases as ischemic heart disease and diabetes mellitus where as the prognostic importance in heart failure and arterial hypertension is more uncertain. In more rare diseases as the inborn long QT syndrome the QT interval gives not only important hint to the diagnosis but the magnitude also provides information on prognosis. QTc has probably no independent prognostic importance in hypertrophic cardiomyopathy or in the arrhythmogenic right ventricular disease. The degree of QTc prolonging during treatment with QTc prolonging drugs is prognostic for the risk of ventricular arrhythmia in form of torsade de pointes and QTc prolonging drugs should probably not be prescribed for patients with a QTc greater than 460 ms and withdrawn if QTc exceeds 500 ms during treatment. Data from the DIAMOND study suggest that QTc can be used to point out those heart failure patients who will benefit from antiarrhythmic therapy.
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PMID:QTc interval in the assessment of cardiac risk. 1211 54


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