Michael F. Caron

Intravenous plus oral amiodarone, atrial septal pacing, or both strategies to prevent post-cardiothoracic surgery atrial fibrillation: The atrial fibrillation suppression trial II (AFIST II)

Background—The effect of a hybrid intravenous and oral prophylactic amiodarone regimen on postcardiothoracic surgery (CTS) atrial fibrillation (AF) is unknown. The impact of active atrial septal pacing on post-CTS AF has not been well characterized. In addition, the effect of using both amiodarone and atrial septal pacing together to prevent atrial fibrillation is unknown. Methods and Results—Patients (n=160) were randomized to amiodarone or placebo and then to pacing or no pacing using a 2×2 factorial design. All therapies began within 6 hours post-CTS. Amiodarone was given by intravenous infusion for the first 24 hours (1050 mg total) followed by oral therapy for 4 postoperative days (4800 mg total). Atrial septal pacing was given for 96 hours. Amiodarone reduced the risk of AF by 43% and the risk of symptomatic AF by 68% (P =0.037 and P =0.019) versus placebo. Atrial septal pacing did not reduce AF or symptomatic AF incidence versus no pacing. The risk of post-CTS AF in the patients receiving amiodarone+pacing was lower than the placebo+no pacing and the placebo+pacing groups (57.9% and 60.5% reductions, P =0.047 and P =0.040, respectively). Conclusions—Amiodarone given as both an intravenous and oral regimen is effective at reducing post-CTS AF but atrial septal pacing is ineffective. Combining amiodarone and pacing is better than placebo with or without pacing but not amiodarone alone.

Influence of Global Region on Outcomes in Heart Failure Beta-Blocker Trials

OBJECTIVES We sought to describe the United States and the rest of the world (ROW) outcomes from the major β-blocker heart failure (HF) trials. BACKGROUND HF trials have demonstrated differences in outcomes by geographic region. METHODS Randomized, double-blind, placebo-controlled studies that evaluated β-blockers in HF patients, had a primary endpoint of mortality, and enrolled U.S. patients were included. Relative risk (RR) was calculated for patients enrolled in the United States and ROW. Meta-analysis of the combined mortality rates was performed using the Cochran-Mantel-Haenszel statistic, stratified by study. RESULTS A total of 8,988 patients were enrolled in the MERIT-HF (Metoprolol Controlled-Release Randomized Intervention Trial in Heart Failure), COPERNICUS (Carvedilol Prospective Randomized Cumulative Survival trial), and BEST (β-Blocker Evaluation of Survival Trial) combined; 4,198 (46.7%) were from the United States. In the U.S. cohort, the RR reduction for each β-blocker was of smaller magnitude than in the overall cohort and no longer significant, whereas in the ROW subgroup, the mortality benefit for β-blockade persisted. In the pooled analysis (n = 11,635), the RR of death was reduced by 23% (p < 0.001) with β-blockade compared with placebo. In contrast, the mortality reduction associated with β-blockade in the U.S. cohort was small and not statistically significant (RR: 0.92, 95% confidence interval [CI]: 0.82 to 1.02, p = 0.11). The survival benefit persisted in the ROW cohort (RR: 0.64, 95% CI: 0.56 to 0.72, p < 0.001). CONCLUSIONS Among patients enrolled in the United States, β-blockade was associated with a lower magnitude of survival benefit, whereas the ROW response was similar to the total study population. This geographic difference in treatment response may be a reflection of population differences, genetics, cultural or social differences in disease management, or low power and statistical chance.

Electrocardiographic and Hemodynamic Effects of Panax Ginseng

OBJECTIVE: To determine whether Panax ginseng ingestion can acutely or chronically alter electrocardiographic parameters: PR, QRS, QT, QTc, and RR intervals, and QT and QTc interval dispersion. Effects of P. ginseng on blood pressure and heart rate also were evaluated. METHODS: This is a prospective, randomized, double-blind, placebo-controlled study of healthy adults at the University of Connecticut. Thirty subjects were randomly allocated to receive 28 days of therapy with either P. ginseng extract 200 mg or placebo. Baseline 12-lead electrocardiograms (ECGs) were obtained. Subsequent ECGs were performed following study drug ingestion at 50 minutes, 2 hours, and 5 hours on days 1 and 28. Blood pressure readings were taken with each ECG. RESULTS: P. ginseng ingestion increased the QTc interval by 0.015 seconds on day 1 at 2 hours compared with the placebo group (p = 0.03). It also reduced diastolic blood pressure from 75 ± 5 mm Hg at baseline to 70 ± 6 mm Hg at the same time point (p = 0.02). The observed effects are not believed to be clinically significant. No other statistically significant changes were found in electrocardiographic or hemodynamic variables on days 1 or 28. CONCLUSIONS: P. ginseng, at doses of 200 mg of the extract daily, increases the QTc interval and decreases diastolic blood pressure 2 hours after ingestion in healthy adults on the first day of therapy.

Evaluation of the Antihyperlipidemic Properties of Dietary Supplements

We reviewed the published literature regarding the antihyperlipidemic effects of dietary supplements. A search of MEDLINE database, EMBASE Drugs and Pharmacology database, and the Internet was performed, and pertinent studies were identified and evaluated. References from published articles and tertiary references were used to gather additional data. Published trials indicate that red yeast rice, tocotrienols, gugulipid, garlic, and soy protein all have antihypercholesterolemic effects. These supplements, as well as ω‐3 fatty acids, also have antihypertriglyceridemic effects. In clinical trials none of the agents led to a reduction in low‐density lipoproteins greater than 25%, suggesting modest efficacy. When recommending these supplements, clinicians should keep in mind that their long‐term safety is not established and patients should be monitored closely.

Effect of diuresis on P-wave duration and dispersion.

Study Objective. To evaluate the effects of changing volume status on P‐wave duration and dispersion in patients with decompensated heart failure.

An evaluation of the change in electrocardiographic P-wave variables after acute caffeine ingestion in normal volunteers

Background: Caffeine’s effect on supraventricular dysrhythmias is poorly understood, and establishing a marker to predict atrial fibrillation may help to explain supraventricular dysrhythmias caused by caffeine.

Effects of Intravenous Magnesium Sulfate on the QT Interval in Patients Receiving Ibutilide

Study Objective. To determine the effect of intravenous magnesium sulfate on the QT and QTc intervals in patients receiving ibutilide for immediate chemical cardioversion of atrial flutter or fibrillation.

The Impact of Catecholamines on Defibrillation Threshold in Patients with Implanted Cardioverter Defibrillators

Objectives: To determine the effect of physiologic catecholamine concentrations on the defibrillation threshold (DFT) in patients with implanted cardioverter defibrillators.

Amiodarone in the New AHA Guidelines for Ventricular Tachyarrhythmias

OBJECTIVE: To delineate amiodarones role in the new American Heart Association guidelines for ventricular tachyarrhythmias, review the literature that supports the use of amiodarone in ventricular tachyarrhythmias, describe the pharmaceutical properties of amiodarone and elucidate their clinical implications, and discuss the dosing, preparation, and administration of amiodarone. DATA SOURCES: A search of MEDLINE (1966–October 2000) database and EMBASE Drugs and Pharmacology database (1980–October 2000) was performed. References from published articles and tertiary references were used to gather additional data. DATA EXTRACTION: All articles were screened, and pertinent studies were identified and evaluated. DATA SYNTHESIS: Recent trials have demonstrated amiodarones usefulness in the setting of ventricular tachyarrhythmias. Based on these investigations and contrary to past guidelines, amiodarone is included in the 2000 advanced cardiovascular life support guidelines as a possible agent for hemodynamically stable monomorphic ventricular tachycardia (VT), non-QT prolonged polymorphic VT, and ventricular fibrillation (VF)/pulseless VT. Although not specifically evaluated in the setting of hemodynamically stable monomorphic VT and non-QT prolonged polymorphic VT, investigations by the Intravenous Amiodarone Multicenter Trial Group and other clinical trials make amiodarone an acceptable choice for these arrhythmia categories. The results of the ARREST (Resuscitation of Refractory Sustained Ventricular Tachyarrhythmias) trial prove amiodarone to be the antiarrhythmic of choice for VF/pulseless VT. CONCLUSIONS: Amiodarone is classified as a IIb therapeutic intervention for all three arrhythmia categories, which makes it an acceptable, safe, and useful agent with fair to good evidence to support its use. In addition, amiodarone requires careful preparation and delivery to achieve safe and effective outcomes.

Economic Analysis of Intravenous Plus Oral Amiodarone, Atrial Septal Pacing, and Both Strategies to Prevent Atrial Fibrillation After Open Heart Surgery

Study Objectives. To compare the cost‐effectiveness of intravenous plus oral amiodarone, atrial septal pacing, and both strategies combined to prevent atrial fibrillation after open heart surgery. Secondary objectives were to compare the cost‐effectiveness of amiodarone versus no amiodarone and of pacing versus no pacing, and to compare hospitalization costs of the various strategies.