Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The CAST was a randomized, double-blind placebo-controlled multicentre trial of antiarrhythmic medications designed to suppress ventricular arrhythmias in patients after an acute myocardial infarction (MI). A collection of 21 items derived from established scales was used to assess aspects of quality of life in CAST. The questions focused on symptoms, mental health, physical functioning, social functioning, life satisfaction, and life expectancy. Additional aspects included exposure to major stressful life events, and perceived social support and social integration. Work status was also recorded. Using the baseline values of 1465 (98%) out of 1498 patients enrolled in the CAST main study between 15 June 1987 and 19 April 1989, the reliability and validity of the scales used in CAST were computed. High internal consistency reliability (> or = 0.70) was found for Symptoms, Mental Health, and Physical Functioning. The discriminative validity, in particular for Symptoms, Mental Health, Physical and Social Functioning, showed that patients with heart failure and previous MI, as well as those suffering from angina and dyspnea, had a worse quality of life than those patients who were not experiencing these symptoms. It was concluded that the scales selected to form the CAST quality of life questionnaire were both reliable and clinically valid for this patient population and therefore could be used to detect disease progression and treatment effects.
 ...
PMID:Methods for assessing quality of life in the cardiac arrhythmia suppression trial (CAST). 130 Nov 28

The pharmacologic treatment of atrial fibrillation (AF) is aimed at controlling the ventricular response, restoring sinus rhythm, and preventing or delaying relapses. In the control of ventricular response, digitalis maintains a primary role when the arrhythmia is accompanied by heart failure. In ischemic, hypertensive, and degenerative (whose number is increasing at present) cardiopathies without evident ventricular dilatation, treatments with calcium antagonists (such as verapamil, gallopamil, or diltiazem) or beta-blocking agents must be preferred. In order to control the ventricular response in patients with chronic AF during physical activity, the association of digitalis with beta-blocking agents or calcium antagonists seems to provide satisfactory results. The drugs of the IC class, especially flecainide, represent a certain therapeutical progress in the restoration of sinus rhythm in the treatment of paroxysmal atrial fibrillation affecting subjects without evident alterations of ventricular function, particularly in subjects with Wolff-Parkinson-White syndrome, with forms of vagal origin, or with atrial fibrillation alone. A therapeutic combination of digitalis and quinidine may produce resolution of the arrhythmia in the presence of altered ventricular function or when AF is of an uncertain onset. In patients with hypertensive, ischemic, and/or degenerative cardiopathy without evident ventricular or advanced heart failure, the verapamil-quinidine association may also be effective and even quicker. The combination of drugs of the I and III class for restoration of the sinus rhythm in particularly resistant forms of AF without evident structural heart alterations is promising but must be verified in a greater number of patients. In the prevention of relapses amiodarone appears to have the widest spectrum of advantages from an electrophysiologic point of view; however, because of its many side effects, amiodarone represents a late therapeutical choice. The promising results obtained with flecainide are disputed by the results of the CAST, which limit the possibilities of using this drug to a low number of cases (W.P.W. syndrome, AF of vagal origin, atrial fibrillation alone). In the past, quinidine and disopyramide have been the drugs most widely used in the prophylaxis of AF. These drugs have a similar efficacy, and both of them provided some positive results. However, because of untoward side effects (especially for quinidine) during chronic treatment, the use of these drugs has been questioned. Perhaps in the majority of patients, the less dangerous therapeutic choice after the termination of the fibrillation is a combination of drugs slowly down AV node activity (digitalis or calcium antagonists and beta blockers) with class IA antiarrhythmics.
 ...
PMID:The pharmacologic treatment of atrial fibrillation. 167 64

The endpoint of pharmacologic therapy in patients with recurrent paroxysmal atrial fibrillation or in patients with chronic atrial fibrillation successfully cardioverted is to prevent recurrences. Recent studies have cautioned against the use of sodium channel blockers (class I agents) in terms of safety. A number of patients with atrial fibrillation have coronary artery disease and the use of class I agents may be of concern, as suggested by the CAST trial. Recently a concern was also raised, regarding the safety of quinidine following cardioversion of atrial fibrillation. In patients with congestive heart failure on antiarrhythmic therapy, the SPAF trial has shown an increase in cardiac mortality and arrhythmic deaths. In this review a case is made in favor of the use of low-dose amiodarone as a first-line agent in patients with atrial fibrillation. Amiodarone is a potent antiarrhythmic agent with little if any negative inotropic effect and, therefore, is the agent of choice in patients with heart failure. In patients with coronary artery disease, the antianginal properties may be useful, and recent studies have shown a decrease in sudden death in the amiodarone group. Therefore, a number of advantages do exist in favor of the use of amiodarone as a first-line drug, at least in selected indications.
 ...
PMID:Amiodarone as a first-line drug in the treatment of atrial fibrillation: the protagonist viewpoint. 787 75

The usual frequent tachyarrhythmias well known to the specialists in internal medicine, such as ventricular tachycardia and ventricular fibrillation, are not discussed in this publication; nor are the bradycardias connected with the sick sinus syndrome or with atrioventricular block of higher degrees (with one exception). In the first section a stratification of the risk after myocardial infarction is presented including the therapeutic implications. Severely reduced left ventricular function is of most negative prognostic value. After the poor results of the CAST study, which revealed a threefold greater mortality of patients with myocardial infarction and severely impaired left ventricular function under treatment with some antiarrhythmic agents of class I (Vaughan Williams), compared to patients on placebo, cardiologists have resorted to beta-blocking agents again or, in patients with severely reduced left ventricular function, to amiodarone (Cordarone), based on preliminary results of current amiodarone studies. For selected patients, implantable cardioverter-defibrillator (ICD) devices seem to have a promising future. In the second part some rare and persistent arrhythmias are mentioned that may induce heart failure in an otherwise healthy heart, such as ectopic atrial tachycardia, atrioventricular junctional tachycardia with RP > PR, His bundle tachycardia and idiopathic ventricular tachycardia (this arising only in infants). In the third section some infrequent forms of tachycardia are discussed that may be sporadically encountered in a medical office. Ventricular tachycardia of the type "torsades de pointes" is associated with on a prolonged QT or QTU time in the ECG and is mainly due to drugs (especially antiarrhythmic agents). The therapy consists in withdrawal of the drug and may include magnesium intravenously and even a temporary pacemaker. The tachycardias associated to the Wolff-Parkinson-White syndrome have gained more practical importance since it has become possible to localize the accessory pathway involved by mapping with subsequent interruption by surgery or ablation. In atrial fibrillation with an ECG pattern of delta waves at the beginning of QRS complexes, digitalis and verapamil are contraindicated since they may induce ventricular fibrillation. The Mobitz type is one, and the most rare, form of the three atrioventricular blocks of second degree. It is almost always combined with an infra-His-bundle conduction disturbance in the conducted beats, and is an immediate precursor of complete atrioventricular block. Patients with the Mobitz block usually need a pacemaker. Finally, two case reports are presented to show that superficial and incorrect diagnosis of an arrhythmia is followed by incorrect and dangerous therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Dangerous arrhythmias]. 849 70

After a brief classification of antiarrhythmic drugs and their mode of action, ventricular dysrhythmias are defined and characterized with respect to underlying causes. A short chapter is dedicated to the treatment of acute ventricular tachycardia, a longer one to the prophylaxis of ventricular dysrhythmias, based on our knowledge in the "post CAST Study era' (CAST = Cardiac Arrhythmia Suppression Trial). A special interest is dedicated to patients commonly encountered in daily practise: patients with coronary artery disease, patients with chronic heart failure, and patients without underlying heart disease. Then a separate assessment is made of the proarrhythmic effects of antiarrhythmic drugs.
 ...
PMID:[Ventricular arrhythmias: diagnosis and drug therapy]. 868 56

In recent years, the results of large randomized and controlled trials of antiarrhythmic agents for primary and secondary prevention of ventricular tachycardia and ventricular fibrillation have changed perceptions of the actions of antiarrhythmic agents regarding both efficacy and risk. The premature termination of the CAST trials of primary prevention in postinfarct patients highlighted the proarrhythmic risk and inefficacy of the sodium channel blockers (class I action), encainide, flecainide, and moricizine, in patients at relatively low risk for death in the long term. The excess mortality with therapy was attributed to proarrhythmia due to facilitation of reentry, especially during acute ischemia. About the same time, European trials with amiodarone, a complex agent with antiadrenergic action and powerful action to prolong refractoriness (class III action), indicated enhanced survival after infarction with amiodarone but not with agents with class I action. Recent verbal reports of larger and placebo-controlled trials (EMIAT and CAM-IAT) confirm a significant reduction in arrhythmia mortality, possibly with a favorable trend in total mortality. While an older trial with dl-sotalol (class III and beta-blocking actions) showed a trend toward improved survival after infarction, a recent trial with d-sotalol in patients with recent infarction or remote infarction and heart failure was prematurely terminated because of excess mortality attributed to proarrhythmia (torsades de pointes), indicating the importance of beta-blocking properties of a class III agent. A secondary prevention trial (ESVEM) in patients surviving an episode of VT or VF showed significant superiority of dl-sotalol compared to an array of agents that block sodium channels with respect to both efficacy and tolerance. Occurrence rates of arrhythmias treated with drugs tested for efficacy either by suppression of inducible arrhythmias or by suppression of spontaneous ectopy were higher and equivalent for both testing methods. A secondary prevention trial of amiodarone and multiple agents that block sodium channels in survivors of cardiac arrest (CASCADE) showed a significant increased efficacy of amiodarone but poorer long-term tolerance compared with the other agents. Comparative analysis of the results of the various trials suggests that class III action coupled with antiadrenergic action is more efficacious in both primary and secondary prevention of life-threatening ventricular arrhythmias and that lethal proarrhythmias may be the predominant effect in attempts at primary prevention in low-risk populations due to class I or so-called pure class III action.
 ...
PMID:From first class to third class: recent upheaval in antiarrhythmic therapy--lessons from clinical trials. 878 Mar 26

To compare the medical treatment of heart failure 30 years ago and at present implies more than the report of new therapeutic strategies and their application. First of all, there is a change in pathophysiological concepts: 30 years ago the therapeutic aim was the increase of myocardial contractility, currently afterload reduction without reactive activation of the sympatho-neuronal and of the renin-angiotensin system is aimed. In contrast to the situation 30 years ago, nowadays new therapeutic strategies can no longer be based on pathophysiological considerations or the demonstration of a potentially beneficial acute effect. The efficacy of any new treatment for heart failure has to be evaluated by controlled randomized trials with the primary end point of prolongation of life. The treatment of chronic heart failure 30 years ago was essentially based on general methods and on the application of diuretics and digitalis. Improved survival of patients with heart failure was first documented by afterload reduction with hydralazine/isosorbide dinitrate. Further improvement was achieved by application of ACE-inhibitors. For diuretics no results are available indicating improved prognosis. For digitalis two studies indicate symptomatic but no prognostic improvement. The treatment of heart failure with betablockers is not yet finally decided. Especially in the post-CAST area the drug treatment of ventricular tachyarrhythmias is very problematic. Class I antiarrhythmic drugs should generally be rather avoided. The application of betablockers or class III antiarrhythmic drugs maybe considered, although there is no proof. In symptomatic patients the implantation of a cardioverter/defibrillator system may be preferred.
 ...
PMID:[Cardiology. I. Heart failure]. 946 3

Immunoglobulin mu binding protein 2 (IGHMBP2) is a DNA/RNA helicase with a putative role in transcriptional regulation and splicing. A recessive mutation of the Ighmbp2 gene in neuromuscular degeneration (nmd) mice causes progressive neurogenic atrophy of limb muscles. Affected mice show significant loss of motor neurons with large caliber axons and a moderate reduction of neurons with small caliber axons in the ventral nerve roots of the spinal cord. To investigate the role of Ighmbp2 in the pathogenesis of neuromuscular degeneration, we generated two independent lines of transgenic mice expressing the full-length Ighmbp2 cDNA specifically in neurons. Histopathological evaluation of L4 ventral nerve roots revealed that transgenic expression of the Ighmbp2 cDNA prevented primary motor neuron degeneration, while restoring the normal axonal morphology and density in nmd mice. A similar neuronal improvement is found in mutant mice carrying the CAST/EiJ-derived modifier of nmd (Mnm(C)). Intriguingly, both the transgenic and modified nmd mice went on to develop a previously unobserved cardiac and skeletal myopathy. Necropsy of nmd mice in end-stage heart failure revealed a primary dilated cardiomyopathy with secondary respiratory failure that was confirmed by in vivo ECG and echocardiographic measures. Our results suggest that reduced levels of IGHMBP2 in nmd mice compromise the integrity and function not only of motor neurons but also of skeletal and cardiac myocytes. These findings highlight the important role of IGHMBP2 in the maintenance and survival of these terminally differentiated cell types.
 ...
PMID:Transgenic rescue of neurogenic atrophy in the nmd mouse reveals a role for Ighmbp2 in dilated cardiomyopathy. 1506 27

beta-Adrenoceptor antagonists (beta-blockers) provide multiple benefits to patients with coronary artery disease. The 2001 American Heart Association and American College of Cardiology (AHA/ACC) guidelines for secondary prevention of myocardial infarction (MI) recommend initiating beta-adrenoceptor blockade in all post-MI patients and continuing therapy indefinitely. Atenolol and metoprolol have been shown to decrease vascular mortality in the acute-MI period. In the post-MI period timolol provided a 39% reduction in mortality in the Norwegian Multicenter Study group and propranolol was associated with a 26% reduction in mortality in BHAT (Beta-blocker Heart Attack Trial). beta-Adrenoceptor antagonist therapy results in reduction of myocardial oxygen demand and is therefore also effective for the treatment of angina pectoris. In CAST (Cardiac Arrhythmia Suppression Trial) beta-adrenoceptor antagonist therapy was associated with a significant reduction in arrhythmic death or cardiac arrest. In the post-MI amiodarone trials EMIAT (European Myocardial Infarct Amiodarone Trial) and CAMIAT (Canadian Amiodarone Myocardial Infarction Trial) there was a mortality benefit and decreased arrhythmic death in patients who received both amiodarone and beta-adrenoceptor antagonist therapy, compared with patients receiving amiodarone therapy alone. In the post-MI defibrillator (implantable cardioverter defibrillator [ICD]) trials, AVID (Antiarrhythmic Versus Implantable Defibrillator) and MUSTT (Multicenter Unsustained Tachycardia Trial), beta-adrenoceptor antagonist therapy was independently associated with improved overall survival. The exception was the ICD patients in MUSTT, and the benefit was attenuated in the amiodarone and ICD patients in AVID.AHA/ACC guidelines recommend the use of beta-adrenoceptor antagonists in all patients with symptomatic left ventricular dysfunction, based on several large, controlled heart failure trials. Extended-release metoprolol succinate reduced all-cause mortality by 34% in MERIT-HF (Metoprolol Controlled-Release/Extended-Release Randomized Intervention Trial in Heart Failure). Bisoprolol was associated with a 34% mortality benefit in CIBIS-II (Cardiac Insufficiency Bisoprolol Study II) and carvedilol was associated with a 35% mortality reduction in the COPERNICUS (Carvedilol Prospective Randomized Cumulative Survival) trial. beta-Adrenoceptor antagonists reduce perioperative mortality in patients undergoing cardiac as well as non-cardiac surgery; however, they remain underutilised. Contraindications to beta-adrenoceptor antagonist therapy include severe bradycardia, high-grade atrioventricular block, marked sinus node dysfunction and acute exacerbations of heart failure. Many of the perceived adverse effects of beta-adrenoceptor antagonists have not been substantiated by large clinical trials.beta-Adrenoceptor antagonists differ with regard to receptor selectivity, receptor affinity, lipophilicity and intrinsic sympathomimetic activity. Beneficial properties of beta-adrenoceptor antagonists may not always be extrapolated as a class effect, and patient selection and drug preparations should follow trial guidelines. The beneficial effects of beta-adrenoceptor antagonists are clearly proven in cardiac patients and those at risk for cardiac disease. They are indicated for heart failure and proven beneficial in patients undergoing cardiac and non-cardiac surgery. These benefits appear to be consistent across most patient subgroups. beta-Adrenoceptor antagonists are generally well tolerated, yet significant morbidity and mortality result from their continued underutilisation.
 ...
PMID:Optimising the use of beta-adrenoceptor antagonists in coronary artery disease. 1581 91