Michael A. Brodsky

Efficacy and Safety of Oral Dofetilide in Converting to and Maintaining Sinus Rhythm in Patients With Chronic Atrial Fibrillation or Atrial Flutter The Symptomatic Atrial Fibrillation Investigative Research on Dofetilide (SAFIRE-D) Study

BackgroundThis double-blind, multicenter, placebo-controlled study determined the efficacy and safety of dofetilide in converting atrial fibrillation (AF) or atrial flutter (AFl) to sinus rhythm (SR) and maintaining SR for 1 year. Methods and ResultsPatients with AF or AFl (n=325) were randomized to 125, 250, or 500 &mgr;g dofetilide or placebo twice daily. Dosages were adjusted for QTc response and, after 105 patients were enrolled, for calculated creatinine clearance (ClCr). Pharmacological cardioversion rates for 125, 250, and 500 &mgr;g dofetilide were 6.1%, 9.8%, and 29.9%, respectively, versus 1.2% for placebo (250 and 500 &mgr;g versus placebo;P =0.015 and P <0.001, respectively). Seventy percent of pharmacological cardioversions with dofetilide were achieved in 24 hours and 91% in 36 hours. For the 250 patients who successfully cardioverted pharmacologically or electrically, the probability of remaining in SR at 1 year was 0.40, 0.37, 0.58 for 125, 250, and 500 &mgr;g dofetilide, respectively, and 0.25 for placebo (500 &mgr;g versus placebo, P =0.001). Two cases of torsade de pointes occurred, 1 on day 2 and the other on day 3 (0.8% of all patients given active drug); 1 sudden cardiac death, classified as proarrhythmic, occurred on day 8 (0.4% of all patients given active drug). ConclusionsDofetilide, a new class III antiarrhythmic agent, is moderately effective in cardioverting AF or AFl to SR and significantly effective in maintaining SR for 1 year. In-hospital initiation and dosage adjustment based on QTc and ClCr are necessary to minimize a small but nonnegligible proarrhythmic risk.

Factors determining maintenance of sinus rhythm after chronic atrial fibrillation with left atrial dilatation

Successful therapy of atrial fibrillation (AF) has been reportedly influenced by a variety of factors including patient age, type of underlying heart disease, duration of arrhythmia, left ventricular function and left atrial (LA) size. To determine which of these factors are associated with maintenance of sinus rhythm after conversion, 43 patients with symptomatic chronic AF in the setting of a dilated left atrium (greater than or equal to 45 mm, range 45 to 78) were followed for at least 6 months after the return of sinus rhythm. Class IA drugs, IC drugs or amiodarone were used for therapy. Life table analysis showed sinus rhythm to be maintained in 81% for 6 months, 79% for 12 months and 60% for 24 months. Factors positively associated with success were conversion with drug therapy alone, duration of chronic AF less than or equal to 1 year, absence of mitral valve disease and LA dimension less than or equal to 60 mm (all p less than 0.05). Patient age, left ventricular function and presence of coronary disease were not associated with outcome. Thus, patients with moderate LA dilatation (45 to 60 mm) and a short duration of chronic AF can often be maintained in sinus rhythm, especially if they convert with pharmacologic intervention alone.

Amiodarone for maintenance of sinus rhythm after conversion of atrial fibrillation in the setting of a dilated left atrium

Previous reports suggest that the finding of left atrial (LA) dilatation (greater than 45 mm) by echocardiography identifies patients not likely to maintain sinus rhythm after conversion of atrial fibrillation (AF). However, these studies antedate the availability of amiodarone, an antiarrhythmic agent that reportedly is effective in patients with AF in whom other drug therapy has failed. To analyze the relation between LA size and the ability to maintain sinus rhythm with amiodarone therapy, 28 patients, aged 32 to 87 years (mean 61), with an LA dimension greater than 45 mm (range 46 to 78, mean 57) were studied. Thirteen patients (46%) had valvular heart disease, 10 (36%) dilated cardiomyopathy and 5 (18%) miscellaneous disorders. In 25 patients (89%) quinidine therapy had failed. After therapy with amiodarone, sinus rhythm returned in all patients and was maintained. Therapy was judged completely successful in 10 patients (alive and still in sinus rhythm with at least 1 year of follow-up), partially successful in 11 (maintaining sinus rhythm for at least 6 months before a change in status) and failed in 7. Completely successful therapy was accomplished in 9 of 18 patients with an LA dimension between 46 and 60 mm, but in only 1 of 10 patients with an LA dimension greater than 60 mm (p less than 0.05). Thus, patients with LA dimensions between 46 and 60 mm who are significantly compromised by AF can often be maintained in sinus rhythm with amiodarone therapy. However, in patients with larger LA dimensions. AF is likely to return despite aggressive antiarrhythmic therapy with amiodarone, a drug with potentially serious side effects.

New-onset ventricular tachycardia during pregnancy

During evaluation for palpitations, presyncope, or syncope, seven pregnant women had documented ventricular tachycardia. Before pregnancy none had a history of significant cardiac disease or symptomatic arrhythmia. The tachycardia rate ranged from 117 to 250 beats/min and lasted up to 65 seconds. Arrhythmia evaluation in five of the patients suggested catecholamine-sensitive ventricular tachycardia. This diagnosis was supported by either a positive relation to exercise or isoproterenol infusion, suppression of arrhythmia by beta-blockade or sleep, and lack of induction of arrhythmia by programmed electrical stimulation of the heart. The arrhythmias resolved in one patient soon after evaluation and in one other patient after 2 months of controlling therapy. Five other patients continued to receive therapy throughout pregnancy. Delivery was accomplished in all patients without significant maternal or neonatal complications.

Magnesium and potassium therapy in multifocal atrial tachycardia

Eight patients with multifocal atrial tachycardia received 7 to 12 gm of magnesium sulfate intravenously over a 5-hour period. Potassium supplements were given initially or added later. Initial arterial blood gases showed mean pH 7.48 +/- 0.03, PcO2 39.7 torr, PO2 72 torr, HCO-3 29.8 +/- 4.5 mEq/L, and base excess 6.84 +/- 3.78 mEq/L. Initial serum magnesium correlated well with initial serum potassium. Three patients had subnormal levels of magnesium and potassium. The level of serum magnesium rose with an intravenous injection magnesium and serum potassium levels tended to fall unless they were supplanted with potassium. There were seven patients who retained more than 20 mEq of the infused magnesium. Multifocal atrial tachycardia was successfully converted to sinus rhythm or sinus tachycardia in seven patients. Multifocal atrial rhythm (at slow rate) persisted in one patient. Two patients with falling serum potassium levels required potassium supplements. Results of this study confirm that patients with multifocal atrial tachycardia respond favorably to parenteral magnesium and potassium. We believe that serum magnesium administered together with serum potassium stabilizes the ionic balance of atrial cells and thus prevents spontaneous ectopy.

Life-threatening ventricular arrhythmias due to transient or correctable causes: high risk for death in follow-up

OBJECTIVES This study evaluated the prognosis of patients resuscitated from ventricular tachycardia (VT) or ventricular fibrillation (VF) with a transient or correctable cause suspected as the cause of the VT/VF. BACKGROUND Patients resuscitated from VT/VF in whom a transient or correctable cause has been identified are thought to be at low risk for recurrence and often receive no primary treatment for their arrhythmias. METHODS In the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial, patients with a potentially transient or correctable cause of VT/VF were not eligible for randomization. The mortality of these patients was compared with the mortality of patients with a known high risk of recurrence of VT/VF in the AVID registry. RESULTS Compared with patients having high risk VT/VF, those with a transient or correctable cause for their presenting VT/VF were younger and had a higher left ventricular ejection fraction. These patients were more often treated with revascularization as the primary therapy, more commonly received a beta-blocker, less often required therapy for congestive heart failure and less commonly received either an antiarrhythmic drug or an implantable cardioverter defibrillator. Nevertheless, subsequent mortality of patients with a transient or correctable cause of VT/VF was no different or perhaps even worse than that of the primary VT/VF population. CONCLUSIONS Patients identified with a transient or correctable cause for their VT/VF remain at high risk for death. Further research is needed to define truly reversible causes of VT/VF. Meanwhile, these patients may require more aggressive evaluation, treatment and follow-up than is currently practiced.

Beta-blocker use and survival in patients with ventricular fibrillation or symptomatic ventricular tachycardia: the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial.

OBJECTIVES To evaluate whether use of beta-adrenergic blocking agents, alone or in combination with specific antiarrhythmic therapy, is associated with improved survival in persons with ventricular fibrillation (VF) or symptomatic ventricular tachycardia (VT). BACKGROUND The ability of beta-blockers to alter the mortality of patients with VF or VT receiving contemporary medical management is not well defined. METHODS Survival of 1,016 randomized and 2,101 eligible, nonrandomized patients with VF or symptomatic VT followed in the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial through December 31, 1996 was assessed using Cox proportional hazards analysis. RESULTS The 817 (28%) patients discharged from hospital receiving beta-blockers had less ventricular dysfunction, fewer symptoms of heart failure and a different pattern of medication use compared with patients not receiving beta-blockers. Before adjustment for important prognostic variables, beta-blockade was not significantly associated with survival in randomized or in eligible, nonrandomized patients treated with specific antiarrhythmic therapy. After adjustment, beta-blockade remained unrelated to survival in randomized or in eligible, nonrandomized patients treated with amiodarone alone (n = 1142; adjusted relative risk [RR] = 0.96; 95% confidence interval [CI] 0.64-1.45; p = 0.85) or a defibrillator alone (n = 1347; adjusted RR = 0.88; 95% CI 0.55 to 1.40; p = 0.58). In contrast, beta-blockade was independently associated with improved survival in eligible, nonrandomized patients who were not treated with specific antiarrhythmic therapy (n = 412; adjusted RR = 0.47; 95% CI 0.25 to 0.88; p = 0.018). CONCLUSIONS Beta-blocker use was independently associated with improved survival in patients with VF or symptomatic VT who were not treated with specific antiarrhythmic therapy, but a protective effect was not prominent in patients already receiving amiodarone or a defibrillator.

Significance of magnesium in congestive heart failure

Electrolyte balance has been regarded as a factor important to cardiovascular stability, particularly in congestive heart failure. Among the common electrolytes, the significance of magnesium has been debated because of difficulty in accurate measurement and other associated factors, including other electrolyte abnormalities. The serum magnesium level represents < 1% of total body stores and does not reflect total-body magnesium concentration, a clinical situation very similar to that of serum potassium. Magnesium is important as a cofactor in several enzymatic reactions contributing to stable cardiovascular hemodynamics and electrophysiologic functioning. Its deficiency is common and can be associated with risk factors and complications of heart failure. Typical therapy for heart failure (digoxin, diuretic agents, and ACE inhibitors) are influenced by or associated with significant alteration in magnesium balance. Magnesium therapy, both for deficiency replacement and in higher pharmacologic doses, has been beneficial in improving hemodynamics and in treating arrhythmias. Magnesium toxicity rarely occurs except in patients with renal dysfunction. In conclusion, the intricate role of magnesium on a biochemical and cellular level in cardiac cells is crucial in maintaining stable cardiovascular hemodynamics and electrophysiologic function. In patients with congestive heart failure, the presence of adequate total-body magnesium stores serve as an important prognostic indicator because of an amelioration of arrhythmias, digitalis toxicity, and hemodynamic abnormalities.

Magnesium therapy in new-onset atrial fibrillation

Abstract In new-onset atrial fibrillation (AF), digoxin has a limited ability to control ventricular response, is no better than placebo for facilitating conversion to sinus rhythm, and has a slow onset of action with a narrow toxic-therapeutic ratio.1,2 Magnesium (Mg) has been shown to slow and sometimes normalize the heart rhythm in supraventricular tachyarrhythmias.3,4 A randomized trial found Mg prevents AF in patients after cardiac surgery.5 Because of these factors, we conducted a prospective, randomized, double-blind, placebo-controlled study addressing whether Mg and digoxin were superior to digoxin alone in controlling the ventricular response of AE.

Magnesium sulfate therapy for sustained monomorphic ventricular tachycardia

Abstract A variety of supraventricular and ventricular arrhythmias have responded favorably to therapy with intravenous magnesium sulfate (MgSO 4 ) regardless of the patients initial serum magnesium level. 1–9 The ventricular arrhythmia most commonly reported to be responsive to MgS 4 is torsades de pointes. 3,5–7,9 We report the responses of 11 patients with sustained monomorphic ventricular tachycardia (VT) to a bolus injection of MgSO 4 .