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)

Oral sotalol was given to 64 patients (78% postinfarction) with recurrent, reentrant ventricular tachycardia (VT) during an average follow-up period of 19.7 months. Fifty-nine (92%) patients had previously experienced recurrent ventricular tachycardia, in spite of having received an average of three conventional antiarrhythmic drugs (13 had previously failed on other Class III drugs). The nature and mechanism of the VT was proved with electrophysiologic testing (EPS), and the chronic sotalol dosage was determined by repeated EPS at 3- to 4-day intervals until the VT was no longer inducible. Sotalol failed in five patients and was discontinued in six patients because of severe side effects (three proarrhythmic effects, including two with torsades de pointes)--a total of 18%. Sotalol was successful alone in 42 patients (65%) and in combination with another antiarrhythmic drug in 11 patients (18%). The average dose of sotalol required for success was 589 mg; 658 mg was the mean daily dose when given alone and 486 mg when given in combination. Side effects were common and were due mainly to the beta-blocking effects of sotalol. Dual chamber pacing was required by 11 patients because of poorly tolerated bradycardia, and 14 patients remained symptomatic from worsening of the cardiac failure in spite of pacing, increased diuretics, or vasodilator therapy. The average drug dosage was the same for symptomatic (680 mg) and asymptomatic (627 mg) patients. Sotalol is a valuable antiarrhythmic drug for reentrant ventricular tachycardia. High doses are needed, and at these doses the beta-blocking activity is responsible for most of the side effects.
 ...
PMID:Efficacy of oral sotalol in reentrant ventricular tachycardia. 227 91

Beta-adrenergic blocking agents may have negative inotropic effects that are particularly worrisome in patients with depressed cardiac function. Their membrane-stabilizing properties may be a contributing factor. Sotalol is currently thought not to cause significant myocardial depression. Intravenous sotalol administration has minimal effects on resting stroke volume, although heart rate and consequently cardiac output are significantly decreased. Systolic blood pressure decreases, with a minimal change in diastolic or mean pressure. Hemodynamic effects are usually seen within 15 to 20 minutes of administration. Hemodynamic indexes are maintained even in patients with mildly depressed ejection fractions (mean ejection fraction of 43 +/- 15%) after oral sotalol administration. Although heart rate decreases, cardiac index is unchanged because of a significant increase in stroke volume index. The latter results from an increase in preload (secondary to bradycardia) and a decrease in afterload. Sotalol is well tolerated, although occasionally it may cause worsening heart failure. This is seen in patients with markedly depressed left ventricular function and inadequate cardiac reserve characterized by an inability to increase stroke volume and cardiac output with exercise. Long-term (1-year) patient follow-up reveals no significant hemodynamic deterioration from initial values obtained after oral administration.
 ...
PMID:Hemodynamic effects of intravenous and oral sotalol. 240 32

Sotalol is a nonselective beta-adrenergic blocking agent with Vaughn-Williams class III activity. Its efficacy was tested in 9 patients with sustained ventricular tachycardia (VT) that had previously remained inducible during electrophysiologic testing of type I drugs (procainamide or quinidine). Eight patients had coronary artery disease with remote myocardial infarction and 1 had cardiomyopathy (ejection fraction 0.34 +/- 0.08, mean +/- standard deviation). Type I drugs prolonged the effective refractory period of the right ventricle 12 +/- 14% and prolonged the VT cycle length 41 +/- 24%. In contrast, despite an equivalent effect on the effective refractory period, a sustained VT could no longer be initiated in any of the 8 patients ultimately tested while taking oral sotalol. Daily doses averaged 600 +/- 103 mg and blood levels associated with VT suppression in electrophysiologic studies were generally greater than 3,000 ng/ml. In addition, sotalol was moderately effective at reducing ventricular ectopic activity measured by ambulatory electrocardiography. Over a mean follow-up of 23 months (range 1 to 37), mild heart failure (3 patients), symptomatic brady-cardia requiring pacemaker (1) and drug-related polymorphous VT (1) have occurred. Sudden death occurred in 1 patient and nonfatal VT recurrence was noted in 2. Five of 8 chronically treated patients currently are successfully treated with minimal side effects. Sotalol appears to be a promising antiarrhythmic drug in the treatment of serious ventricular arrhythmias, even in patients refractory to type I antiarrhythmic agents.
 ...
PMID:Enhanced efficacy of oral sotalol for sustained ventricular tachycardia refractory to type I antiarrhythmic drugs. 312 26

beta-Blockers have been in clinical use for 30 years, and have an accepted role in (among others) the treatment of high blood pressure, the secondary prevention of myocardial infarction and the treatment of arrhythmias. Their place in the treatment of heart failure is currently under investigation. The drugs available in the 1970s and early 1980s were subjected to intense investigation. A new generation of beta-blockers, including some such as carvedilol and bucindolol, with vasodilating properties, is now appearing. As yet these later agents have not been the subject of large clinical trials. Clinical practice involves the treatment of individual patients with defined dosages of particular drugs. It is, therefore, not acceptable to base practice on theories derived from the clinical pharmacology of a particular drug, on the results of small trials or on a meta-analysis of results from a number of trials that were individually inadequate. Clinical practice must follow the results of large-scale trials in defined populations. The major trials in hypertension, myocardial infarction, arrhythmias and heart failure provide the best evidence for the use of individual beta-blockers in each of these clinical situations. In patients with high blood pressure, beta-blockers do not seem to have any particular advantage over other hypotensive agents. In myocardial infarction, relatively late use of a beta-blocker undoubtedly reduces fatality, though the value of early treatment is less clear. beta-Blockers are not powerful antiarrhythmics, but they do appear to prevent sudden death. Their possible role in heart failure is perhaps the most interesting current field of beta-blocker research. There are very few comparative studies of beta-blockers, and it is difficult to make precise recommendations. None of the new generation of beta-blockers has yet been used in a trial that is large enough trial for any of them to be accepted for routine use in preference to older drugs. The use of individual beta-blockers, as with any drug, should follow the results of clinical trials. Propranolol and atenolol have been studied most intensely in hypertension. For secondary prevention of myocardial infarction, the evidence is best for timolol. Sotalol is probably the best antiarrhythmic among the beta-blockers. Whether any individual beta-blocker is best for heart failure remains to be seen.
 ...
PMID:Choosing the right beta-blocker. A guide to selection. 752 29

Impaired left ventricular function after acute myocardial infarction (AMI) is associated with an increased risk of death. Despite recent advances in the management of these patients, sudden death accounts for up to 50% of this mortality, and effective treatment strategies have yet to be identified. Preliminary trials with amiodarone have offered promise that drugs that prolong action potential duration by blocking the potassium channel may be useful in reducing this mortality. The Survival With Oral d-Sotalol (SWORD) trial is a multicenter, multinational study which tests the hypothesis that the class III agent d-sotalol will reduce all-cause mortality in high-risk survivors of AMI. The trial will enroll 6,400 patients with left ventricular dysfunction (ejection fraction < or = 40%) and a recent (6 to 42 days) or a remote (> 42 days) AMI with overt heart failure (New York Heart Association class II or III). In approximately 500 centers throughout the world, men and women aged > or = 18 years will be enrolled and randomized to placebo or d-sotalol (200 mg/day). The minimal follow-up will be 18 months. The trial has a 90% power to detect a 20% reduction in all-cause mortality. The rationale, design, and trial methods are described.
 ...
PMID:Survival with oral d-sotalol in patients with left ventricular dysfunction after myocardial infarction: rationale, design, and methods (the SWORD trial). 774 82

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of sotalol hydrochloride are reviewed. The chemical name of sotalol hydrochloride is 4'-[1-hydroxy-2-(isopropylamino)ethyl]methanesulfonanilide monohydrochloride. Sotalol is a class III antiarrhythmic that prolongs the action potential and refractoriness of cardiac tissue and has potent nonselective beta-blocking activity. Sotalol is well absorbed after oral administration. The pharmacokinetics of sotalol can be described by an open, linear, two-compartment model. The drug is eliminated primarily by the kidneys; mean elimination half-life is 12 hours. Sotalol has been found to be effective in controlling life-threatening ventricular arrhythmias, including sustained ventricular tachycardia, ventricular fibrillation, and premature ventricular complexes. Although sotalol has FDA-approved labeling for use in the treatment of ventricular arrhythmias only, it is also effective against a variety of supraventricular arrhythmias. Noncardiac adverse effects include fatigue, impotence, depression, headache, nausea, diarrhea, and increased triglyceride levels. Cardiovascular adverse effects include atrioventricular block, bradycardia, hypotension, exacerbation of heart failure, and polymorphic ventricular tachycardia. Overall, 11-21% of patients experience adverse effects; 6-18% of these patients have reactions serious enough to warrant the discontinuation of sotalol therapy. The initial dosage of oral sotalol hydrochloride in adults is 80 mg twice daily or 160 mg once daily; the dosage can be increased every three to four days in increments of 40-160 mg/day to a maximum of 480 mg/day. Sotalol is useful in the control of intractable, life-threatening ventricular arrhythmias, as well as a variety of supraventricular arrhythmias, in patients who do not respond to or are intolerant of more conventional antiarrhythmics.
 ...
PMID:Sotalol: a new class III antiarrhythmic agent. 813 5

We explored the central hemodynamic responses to oral sotalol during dose titration in patients with ventricular arrhythmias who underwent programmed ventricular stimulation. Twelve patients were included in the study, 9 with a history of sustained ventricular tachyarrhythmias (6 postmyocardial infarction and 3 with cardiomyopathy) and 3 with a history of nonsustained ventricular tachycardia postmyocardial infarction. Left ventricular ejection fractions were < 45% in 10 patients, and < 35% in 5; the mean ejection fraction was 37% (range 20-51%). Sotalol prevented the induction of ventricular tachycardia in each of 3 patients with nonsustained ventricular tachycardia and in 6 of 9 with sustained ventricular tachycardia at baseline study. At peak action (2 hours) after sotalol loading (mean dose, 167 mg orally twice daily), the hemodynamic effects included bradycardia, decreased cardiac index, increased left ventricular filling pressure and systemic vascular resistance, and no change in stroke volume or stroke work index. One patient was not continued on sotalol, owing to an excessive increase in the pulmonary capillary wedge pressure, despite the lack of symptomatic heart failure. Congestive heart failure in association with marked bradycardia developed in another patient, who had suppression of inducible ventricular tachycardia after sotalol loading; this patient was managed with a reduction in the dose of sotalol and a regimen of digoxin and furosemide, and has been well compensated and without a recurrence of sustained ventricular tachycardia for more than 4 years. Ventricular tachycardia has been controlled with sotalol, without hemodynamic deterioration, in 6 of these patients.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of oral sotalol on systemic hemodynamics and programmed electrical stimulation in patients with ventricular arrhythmias and structural heart disease. 834 25

Two trial designs have been used in evaluating sotalol in patients with sustained tachyarrhythmias: open-label dose escalation and randomized comparison with reference agents. At least 7 open-label studies (n = 16-65) have been reported from single centers in patients in whom trials of numerous other antiarrhythmic agents were unsuccessful. At the doses used, usually 320-640 mg/day, plasma concentrations were in the range associated with both beta blockade and class III antiarrhythmic activity (2-3 micrograms/mL). These concentrations produced electrophysiologic changes that were consistent across studies: 10-16% increase in right ventricular effective refractory period (ERP), 4-8% increase in corrected QT interval (QTc), and 17-30% increase in sinus cycle length (corresponding to a 15-23% decrease in heart rate). In these open-label trials, sotalol suppressed inducible ventricular tachyarrhythmias in 20-72% of patients; the higher degrees of efficacy were reported when induction protocols were confined to double extrastimuli. Side effects leading to discontinuation of sotalol in patients with sustained ventricular tachycardia or fibrillation include fatigue (4.0%), marked bradycardia (3.0%), torsades de pointes (3.0%), and heart failure or pulmonary edema (1.0%). A multicenter randomized trial compared intravenous sotalol with intravenous procainamide in a double-blind prospective fashion. Sotalol suppressed ventricular tachyarrhythmias inducible with triple extrastimuli in 15 (30%) of 50 patients, whereas procainamide was effective in 10 (20%) of 50. In this and other series, responsiveness to sotalol was prospectively identified by a particularly fast tachycardia at baseline (e.g., cycle length of < 270 msec), but not by the extent of changes in global indices of repolarization (QTc, ERP).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Usefulness of sotalol for life-threatening ventricular arrhythmias. 834 27

The evidence that antiarrhythmic compounds that act by slowing conduction velocity increase mortality in patients with cardiac disease is now compelling. Emphasis is now shifting to agents that act by lengthening repolarization and have additional antiadrenergic properties. There is preliminary evidence that pure Class III agents devoid of antisympathetic activity may also increase rather than decrease mortality in certain patients. Thus, in recent years, sotalol and amiodarone have emerged as the preferred agents for the control of most ventricular arrhythmias occurring in the setting of significant heart disease. Sotalol has not been widely studied in postinfarct patients; one trial indicated that the drug did reduce total mortality but the difference did not reach statistical significance. A number of studies with amiodarone in the postmyocardial infarction patients have revealed benefit, but these were from nonblinded studies. Two blinded, placebo-controlled studies are currently ongoing. A potential new indication of amiodarone is in patients with arrhythmias in heart failure in whom amiodarone markedly increased left ventricular ejection fraction, with a pronounced suppressant effect on premature ventricular complexes and nonsustained ventricular tachycardia and a trend for a decrease in mortality in patients with nonischemic cardiomyopathy. The most promising indication of amiodarone in low doses is in the maintenance of sinus rhythm in patients with atrial flutter and fibrillation. For the present, amiodarone appears to be the best prototype of a desirable complex antiarrhythmic compound, if its variegated side effect profile can be favorably modified from knowledge of structure-activity relationships.
 ...
PMID:Expanding indications for the use of Class III agents in patients at high risk for sudden death. 854 10

Antiarrhythmic drug therapy is in a state of continuous flux. In the last decade or so, numerous experimental and clinical studies have revealed that drugs that act by delaying conduction, while markedly suppressing ventricular arrhythmias, have the proclivity to increase mortality in subsets of patients with significant cardiac disease. The adverse impact on mortality was confirmed by placebo-controlled randomized trials as well as meta-analysis of smaller randomized clinical trials. The latter indicated that beta blockers exert a beneficial effect on mortality. Benefit from drugs that lengthen repolarization, especially drugs that have the additional property of blocking sympathetic excitation, was also seen in relatively small numbers of patients. Sotalol and amiodarone fell into this category of antiarrhythmic drugs. There were 2 major consequences that stemmed from the results of these trials. First, the endpoint of clinical trials shifted to total mortality from surrogates such as defined degree of suppression of ventricular arrhythmias. Second, concern regarding increases in mortality produced by class I drugs engendered a shift in favor of drugs that prolong repolarization. Such a shift was bolstered by the growing body of data that established the efficacy of sotalol and amiodarone as potent agents for the control of life-threatening ventricular arrhythmias. They were both found to be superior to class I agents. The perception that the critical factor that mediates their efficacy is the homogeneous prolongation of repolarization has led to the synthesis and characterization of so-called pure class III agents, which include d-sotalol and other lKr blockers such as dofetilide, sematilide, E-4031, and almokalant, among numerous others. The increase in mortality produced by d-sotalol in patients with myocardial infarction and lowered ejection fraction and in patients with and without heart failure has led researchers to question how to design future antiarrhythmic molecules. In the search for an ideal antifibrillatory agent, should emphasis be placed on simple molecules such as pure class III agents or on those with more complex profiles, such as sotalol and amiodarone, which exhibit antiadrenergic actions and the ability to prolong cardiac repolarization? The available data are in favor of the latter approach.
 ...
PMID:The coming of age of the class III antiarrhythmic principle: retrospective and future trends. 878 Mar 25


1 2 3 Next >>