Frank A. McGrew

The effect of diabetes on outcomes of patients with advanced heart failure in the BEST trial

OBJECTIVES This was a retrospective analysis to determine the effect of diabetes on outcome in patients with advanced heart failure (HF), and to determine the effect of beta-blockade in patients with HF with and without diabetes mellitus. BACKGROUND In chronic HF the impact on clinical outcomes and therapeutic response of the prevalent comorbid condition diabetes mellitus has not been extensively investigated. METHODS We assessed the impact of diabetes on prognosis and effectiveness of beta-blocker therapy with bucindolol in patients with HF enrolled in the Beta-Blocker Evaluation of Survival Trial (BEST). We conducted a retrospective analysis to examine the prognosis of patients with advanced HF with and without diabetes, and the effect of beta-blocker therapy on mortality and HF progression or myocardial infarction (MI). The database was the 2,708 patients with advanced HF (36% with diabetes and 64% without diabetes) who were randomized to the beta-blocker bucindolol or placebo in BEST and followed for mortality, hospitalization, and MI for an average of two years. RESULTS Patients with diabetes had more severe chronic HF and more coronary risk factors than patients without diabetes. Diabetes was independently associated with increased mortality in patients with ischemic cardiomyopathy (adjusted hazard ratio 1.33, 95% confidence interval 1.12 to 1.58, p = 0.001), but not in those with a nonischemic etiology (adjusted hazard ratio 0.98, 95% confidence interval 0.74 to 1.30, p = 0.89). Compared with patients without diabetes, in diabetic patients beta-blocker therapy was at least as effective in reducing death or HF hospitalizations, total hospitalizations, HF hospitalizations, and MI. Ventricular function and physiologic responses to beta-blockade were similar in patients with and without diabetes. CONCLUSIONS Diabetes worsens prognosis in patients with advanced HF, but this worsening appears to be limited to patients with ischemic cardiomyopathy. In advanced HF beta-blockade is effective in reducing major clinical end points in patients with and without diabetes.

Efficacy of Esmolol in the Treatment and Transfer of Patients with Supraventricular Tachyarrhythmias to Alternate Oral Antiarrhythmic Agents

The efficacy and safety of esmolol, a titratable intravenous beta‐adrenergic blocking agent with a short elimination hall‐life (t1/2 = 9.0 min) was evaluated in a multicenter open‐label study for the treatment of supraventricular tachyarrhythmias (heart rate greater than 100 bpm). The study also investigated the feasibility of transferring patients from esmolol to alternate oral antiarrhythmic agents without loss of therapeutic response. Of the 113 patients studied, 95 (84%) achieved therapeutic response (reduction in heart rate of 15% or more or conversion to sinus rhythm). Most of these patients (93%) achieved the therapeutic response at esmolol doses of 200 μg/kg/min or lower. Transfer from esmolol to an oral antiarrhythmic agent(s) was studied in 76 patients. Alternate antiarrhythmic agents used in this study were digoxin (N = 25), propranolol (N = 21), verapamil (N = 10), metoprolol (N = 11), quinidine (N = 2), and a combination of two antiarrhythmic agents (N = 7). Sixty‐seven (88%) patients were successfully transferred to oral antiarrhythmic agents without loss of the therapeutic response obtained with esmolol. The most frequent adverse effect observed during the study was hypotension, which resolved quickly (16 ± 14 min) either by decreasing the dose or by discontinuation of esmolol infusion. This study supports previous observations concerning the safety and efficacy of esmolol in the treatment of supraventricular tachyarrhythmias. Furthermore, it demonstrates that the majority of patients successfully treated with esmolol can be safely and effectively transferred to oral therapy with alternate antiarrhythmic agents.

EFFECTIVE CONTROL OF ATRIAL FIBRILLATION CAN BE ACHIEVED WITH VERY LOW DOSES OF AMIODARONE

Background: Amiodarone is the most effective antiarrhythmic agent for the treatment of atrial fibrillation (AF) but its use is limited by side effects related to the cumulative drug exposure. Protocol driven down titration is not commonly employed. We sought to demonstrate the effectiveness and