Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sotalol is a unique beta-blocker that prolongs repolarization. Its use in 626 patients with complex ventricular ectopic activity, as reported in the literature, resulted in suppression of arrhythmia in 50 to 60% of treatment attempts. Detailed analysis of data on arrhythmias in 356 patients that were entered prospectively into a database revealed a median reduction in ventricular premature beats of 76%, compared to a median suppression of repetitive ventricular ectopic activity of 91% and of episodes of nonsustained ventricular tachycardia of 97% (p = 0.002 vs reduction of ventricular premature beats). This marked antiarrhythmic potency of sotalol in repetitive ventricular arrhythmias is thought to be due to its class III activity. Drug efficacy was independent of age, sex, the presence or absence of organic heart disease and the degree of sotalol-induced prolongation of corrected QT interval. Evaluation of left ventricular function in 215 patients treated with the drug demonstrated that depression of left ventricular ejection fraction occurred far less frequently than expected with conventional beta-blockers. Even patients with severely depressed pump function tolerated sotalol surprisingly well. There is a propensity of the drug to aggravate arrhythmia, which resulted in serious proarrhythmic events in 30 (3.5%) of 853 patients. These often consisted of torsades de pointes (9 of 30 patients). Proarrhythmia occurred primarily within the first 3 days of dosing, and exhibited a dose-dependence. In conclusion, sotalol is an effective and well-tolerated antiarrhythmic drug in patients with complex ventricular ectopic activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Efficacy and safety of sotalol in patients with complex ventricular arrhythmias. 128 7

For purposes of clinical management, ventricular arrhythmias have been divided into risk categories of benign, prognostically important (potentially malignant) and malignant. Benign arrhythmias occur in the setting of structurally normal hearts and do not require therapy unless associated with debilitating symptoms. Malignant arrhythmias such as sustained ventricular tachycardia or fibrillation deserve aggressive therapy to prevent recurrence. Arrhythmias occurring in the presence of organic heart disease (often ischemic disease) are frequently asymptomatic but prognostically important as a risk factor for sudden death or cardiac arrest. The common empiric practice to treat such arrhythmias (by about 40 to 50% of cardiologists in the United States) needs to be reassessed in the face of the Cardiac Arrhythmia Suppression Trial. For malignant arrhythmias, class IA agents (procainamide and quinidine) continue to be the standard of treatment, and class IB agents (e.g., mexiletine) may be used as alternative or additive therapy. Class IC agents are used as second-line therapy, especially in the setting of ischemic heart disease. Class III therapy with amiodarone is reserved for refractory patients because of potential toxicity. Sotalol, a new class II-III agent, may become a first-line drug. For prognostically important arrhythmias, beta blockers remain the agents of choice, class IC agents are contraindicated, and class IA or IB drugs, or both, should be used conservatively (i.e., only for symptomatic arrhythmias). For symptomatic but benign arrhythmias requiring treatment, beta blockers are safe although not always effective. Class IA, IB and IC agents may then be considered. In these patients, the proarrhythmic potential of quinidine and class IC agents remains a concern.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical implications of new studies in the treatment of benign, potentially malignant and malignant ventricular arrhythmias. 210 50

The authors envisage the hypothesis of an embryofetal intoxication by a beta-blocker (B-), sotalol, taken by the mother, not hypertensive, during all her pregnancy (160 mg/day). The fullterm newborn, hypotrophic and hypothermic, is suffering from facial dysmorphy with microcephaly, and present a severe tracheal stenosis associated with cardiopathy and important rhythm disorders: bradycardia and permanent bigeminate ventricular extrasystoles for three days. Course is fatal at five months old. On the occasion of this probable intoxication, a brief recall about pharmacology and physiopathology of transplacental passage of B- during pregnancy is done. Then, are enumerated the experimental repercussion of B blockers and their more often theoretical than real undesirable effects, on the fetus. Sotalol is possibly a B-specially aggressive, when it is prescribed abusively, on account of its excellent diffusibility and of its high tissular impregnation.
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PMID:[Possible embryofetopathy caused by beta-blocker (sotalol) taken throughout the pregnancy]. 241 88

A 51-year-old woman was admitted to the hospital for further elucidation of a syncope of unknown origin and exercise-induced tachycardias with broad QRS-complex. The tachycardia was induced by bicycle exercise stress testing, had a frequency of 165/min, showed an inferior axis and left bundle branch block. Organic heart disease was excluded by right and left heart catheterization and selective coronary angiography. A nodoventricular bundle or an atrio-ventricular bundle was excluded by an extensive electrophysiologic study, therefore the documented tachycardia was probably of ventricular origin. However, it was not possible to induce a ventricular tachycardia by programmed ventricular stimulation with up to three extrastimuli even after the infusion of isoprenaline. Sotalol (2 x 160 mg/die) and the combined treatment with mexiletine (2 x 360 mg/die) and disopyramide (2 x 250 mg/die) did not prevent the induction of the tachycardia by exercise testing. The combination of sotalol and flecainide (2 x 100 mg/die) evoked complex ventricular arrhythmias at rest not noted before, and it was therefore withdrawn as well. After all antiarrhythmic drugs were withdrawn verapamil was given in a dose of 3 x 120 mg and this therapy reproduceably prevented the induction of ventricular tachycardia by exercise testing.
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PMID:[Successful treatment of stress-induced therapy refractory ventricular tachycardia with verapamil]. 247 23

251 untreated patients with mild to moderate hypertension were included in a multicenter study aimed 1) to detect arrhythmias (24-H Holter recording) and 2) to assess the efficacy of sotalol on blood pressure and possible arrhythmias. Patients with coronary heart disease or previously documented arrhythmias were excluded. Atrial arrhythmias such as premature beats, fibrillation, flutter and paroxysmal atrial tachycardia were detected in 16% of patients. Monomorphic ventricular premature contractions (VPCs) (Lown I and II) were detected in 41% of patients and polymorphic VPCs or duplets/triplets (Lown III and IV) in 14%. A correlation seems to exist between the level of hypertensive cardiopathy, judged on electrocardiographic data (Tarazi classification), age of patients and severity of arrhythmias. Sotalol was administered during 2 months at a mean dose of 160 mg per day. The treatment was effective on blood pressure and arrhythmias (82% improvement of severe VPCs) and the drug was well tolerated. It was difficult to conclude if these good results are due to the betablocking properties or specific class II antiarrhythmic effects of sotalol or to the combined activity.
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PMID:[Cardiac arrhythmia in moderate arterial hypertension. Epidemiologic survey of 251 cases. Effect of sotalol]. 264 67

Fulguration of the site generator of arrhythmia was attempted in three 31, 33 and 55 year-old patients presenting ectopic atrial tachycardias resistant to various antiarrhythmic medications. Episodes of atrial fibrillation and flutter were also documented in two of them. Two patients had a surgically corrected congenital cardiopathy:interatrial communication or pulmonary stenosis. Mapping of the endocardial emergence point was carried out with electrodes placed 1 cm apart, demonstrating the high atrial origin of the tachycardia, near the right atrium. The auriculogram preceded the earliest possible ectopic P wave by 20 to 70 ms; its multiphasic and prolonged morphology, suggested a local intra-atrial conduction disorder in the three cases. Cathodic shocks were delivered at this site without complications with cumulative energies of 720 J, 480 J and 320 J, respectively. The fulguration was ineffective and revealed other arrhythmic sites in two patients. Only patient n1 has been asymptomatic since 24 months under a treatment with Sotalol 160 mg which had been previously ineffective.
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PMID:[Fulguration of foci of atrial tachycardia in the adult]. 304 46

There were studied 31 patients 20 of them sanes and 11 with sustained systemic arterial hypertension to whom it was administered propranolol and sotalol in different periods. By means of phonomechanocardiographic study it was observed that the contractile heart function didn't present alterations in the sane patients, with the administration of the two drugs. Sotalol produced significative changes with depression of contractility in hypertense patients, even though there were no alterations of the "pump" function. It is probably on account that hypertensive cardiopathy per se has a minor functional myocardiac reserve and the negative inotropic effect is made evident with greater clearness. The fall of the elevation velocity of radial pulse (EVRP) in the two groups, suggests the increase of vascular resistances by the peripheric beta blockade.
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PMID:[Effects of sotalol on ventricular function]. 741 69

Experience with oral sotalol, a beta-blocker with class III-antiarrhythmic properties, is limited in the pediatric population. Sotalol was administered to 32 patients with a mean age of 8.7 years (range 1 day-19.9 years). Mean dosage was 4.6 (1.5-9.4) mg/kg or 122.1 (52-306) mg/m2, respectively. In 27/32 patients, at least 1 antiarrhythmic agent had failed to control the dysrhythmia before sotalol was started. Cardiac diagnoses included normal heart (n = 16), status after correction of congenital heart disease (n = 13), and cardiomyopathy (n = 3). Success (based on symptoms and 24-h electrocardiogram) was achieved in 16/18 patients with reentry supraventricular tachycardia, in 7/8 patients with atrial flutter, and in 4/6 patients with ventricular tachycardia. During a mean follow-up of 15.6 (2-78) months, proarrhythmia occurred in five (16%) patients (symptomatic bradycardia n = 2, QT-prolongation and ventricular extrasystoles n = 1, ventricular extrasystoles n = 1, 2 degrees av-block n = 1), requiring dosage reduction (n = 3), cessation of treatment (n = 1) and pacemaker implantation in one patient, respectively. Symptomatic hypotension was noted in two patients, in whom therapy had to be stopped. Sotalol was a very effective agent for the treatment of various pediatric cardiac dysrhythmias. However, incidence of proarrhythmic effects warrants close electrocardiographic monitoring.
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PMID:[Results of oral sotalol therapy in children with supraventricular and ventricular arrhythmias]. 753 74

Sotalol is an antiarrhythmic medication that has properties of both a beta-blocker and a class III agent and has been used safely and effectively to treat arrhythmias of multiple mechanisms in pediatric patients. The purpose of this study was to review our institutional experience with sotalol in 45 patients with refractory arrhythmias and determine their long-term outcome. Patients responded to sotalol with 80% efficacy and a 22% incidence of adverse side effects. The mean sotalol dose was 116 mg/m2/day, and the average duration of therapy was 15.2 months. In spite of 80% efficacy, only 22% of patients remained on sotalol long-term. Sotalol was discontinued most commonly for either spontaneous resolution of disease or definitive cure by radiofrequency ablation. Other reasons for discontinuation of effective therapy included adverse side effects and arrhythmia control with either an antitachycardia pacemaker or another medication. One patient died while taking sotalol, but this case was considered a failure of treatment rather than an adverse side effect. Of the patients who still receive therapy, several have complex structural heart disease and require a combination of therapies, including sotalol, for adequate rhythm control.
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PMID:Sotalol for refractory arrhythmias in pediatric and young adult patients: initial efficacy and long-term outcome. 757 88

In recent years, there has been a major shift from the use of antiarrhythmic drugs that act by slowing conduction to those that exert their beneficial actions by lengthening cardiac repolarisation. Such a shift is occurring because sodium channel blockers may increase mortality, especially in patients with structural heart disease, and because drugs such as sotalol and amiodarone are effective, with a potential for decreasing arrhythmic mortality. In this context, the electrophysiological and antiarrhythmic properties of d-sotalol, the dextro-isomer of sotalol, are of major importance. d-Sotalol is essentially devoid of beta-blocking actions and may be considered a pure class III compound. It has been assumed that its clinical efficacy would approximate that of amiodarone and sotalol, but without the complex adverse effect profile of amiodarone and the adverse beta-blocker effects of racemic sotalol. d-Sotalol has pharmacokinetic properties that resemble those of the racemate. It lengthens the QT/QTc interval but does not affect other electrocardiographic (ECG) intervals. It increases the refractory period in the atria, ventricles, bypass tracts and the His-Purkinje system while minimally slowing the heart rate. In preliminary studies, it had a weak suppressant effect on premature ventricular contractions, prevented inducibility of ventricular tachycardia or fibrillation in about 40% of patients, and demonstrated the potential to terminate atrial flutter and fibrillation and maintain stability of sinus rhythm during prophylactic administration. The drug exhibits little or no negative inotropic actions. Thus, it is likely to be better tolerated in patients with congestive heart failure dependent on sympathetic stimulation for compensation. Because it produces less bradycardic effect than the racemate, it is believed that the drug might induce a lower rate of torsade de pointes. The role of d-sotalol in controlling cardiac arrhythmias is being addressed in a number controlled clinical trials. However, one such double-blind, placebo-controlled trial, Survival With Oral d-Sotalol (or SWORD), in survivors of myocardial infarction with depressed ventricular function was recently terminated prematurely because of a strikingly greater all-cause mortality compared with placebo (4.6 versus 2.6%). These preliminary findings, still to be fully analysed and interpreted for clinical significance, nevertheless raise valid concerns regarding the currently popular concept of controlling cardiac arrhythmias by the selective or isolated prolongation of repolarisation ('pure' class III action) as an antiarrhythmic principle.
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PMID:Pharmacodynamic, pharmacokinetic and antiarrhythmic properties of d-sotalol, the dextro-isomer of sotalol. 760 Oct 9


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