Jeffrey Kluger

Thiazolidinedione use and post-operative atrial fibrillation: a US nested case-control study.

ABSTRACT Background: Previous investigations suggested thiazolidinediones (TZDs) have the ability to suppress inflammation. Since the pathophysiology of atrial fibrillation (AF) after cardiothoracic surgery (CTS) likely involves an inflammatory mechanism, we sought to determine whether preoperative use of TZDs could further reduce the incidence of post-CTS AF in a population treated with beta-blockers and prophylactic amiodarone. Methods: All diabetic patients over the age of 50 years, not in atrial arrhythmia prior to surgery, who underwent CTS from the Atrial Fibrillation Suppression Trials I, II and III (AFIST I, II and III) were evaluated in this nested case-control study. Patient demographics, surgical characteristics, medication utilization and the incidence of post-CTS AF (AF > 5 minutes duration) were collected as part of AFIST I, II and III. Multivariate logistic regression was used to calculate adjusted odds ratios with 95% confidence intervals (CIs). Results: One hundred and eighty-four diabetic patients were enrolled in the three trials. Overall, the study population averaged 66.9 ± 7.3 years of age, 71.7% were male, 7.1% underwent valve surgery, 4.9% had prior AF, 17.9% had heart failure and 84.2% and 41.8% received postoperative beta-blockade and prophylactic amiodarone, respectively. Forty patients (21.7%) received a preoperative TZD and 144 (78.3%) did not. In total, 66 patients (35.9%) developed post-CTS AF. Upon multivariate logistic regression, the preoperative use of TZDs was found to be associated with a 20% non-statistically significant reduction in post-CTS AF (adjusted odds ratio; 0.80, 95% CI 0.32–1.99; p = 0.63). Limitations: Patients were not randomized to receive TZDs or not. We may not have had adequate power to evaluate our post-CTS AF endpoint. Conclusions: In a diabetic population treated perioperatively with beta-blocker and amiodarone, adjunctive TZD use was associated with a non-statistically significant reduction in a patients odds of developing post-CTS AF. Further research is needed to determine whether TZDs, in fact, do not have anti-fibrillatory effects or whether our study was underpowered to detect a statistically significant benefit with TZDs.

Prevention of Fatal Arrhythmias in High-Risk Subjects by Fish Oil n-3 Fatty Acid Intake

Background— The long-chain n-3 fatty acids in fish have been demonstrated to have antiarrhythmic properties in experimental models and to prevent sudden cardiac death in a randomized trial of post–myocardial infarction patients. Therefore, we hypothesized that these n-3 fatty acids might prevent potentially fatal ventricular arrhythmias in high-risk patients. Methods and Results— Four hundred two patients with implanted cardioverter/defibrillators (ICDs) were randomly assigned to double-blind treatment with either a fish oil or an olive oil daily supplement for 12 months. The primary end point, time to first ICD event for ventricular tachycardia or fibrillation (VT or VF) confirmed by stored electrograms or death from any cause, was analyzed by intention to treat. Secondary analyses were performed for “probable” ventricular arrhythmias, “on-treatment” analyses for all subjects who had taken any of their oil supplements, and “on-treatment” analyses only of those subjects who were on treatment for at least 11 months. Compliance with double-blind treatment was similar in the 2 groups; however, the noncompliance rate was high (35% of all enrollees). In the primary analysis, assignment to treatment with the fish oil supplement showed a trend toward a prolonged time to the first ICD event (VT or VF) or of death from any cause (risk reduction of 28%; P=0.057). When therapies for probable episodes of VT or VF were included, the risk reduction became significant at 31%; P=0.033. For those who stayed on protocol for at least 11 months, the antiarrhythmic benefit of fish oil was improved for those with confirmed events (risk reduction of 38%; P=0.034). Conclusions— Although significance was not achieved for the primary end point, this study provides evidence that for individuals at high risk of fatal ventricular arrhythmias, regular daily ingestion of fish oil fatty acids may significantly reduce potentially fatal ventricular arrhythmias.

Oral amiodarone for prevention of atrial fibrillation after open heart surgery, the Atrial Fibrillation Suppression Trial (AFIST): a randomised placebo-controlled trial

BACKGROUND Beta-blockers and amiodarone reduce the frequency of atrial fibrillation after open-heart surgery but the effectiveness of oral amiodarone in older patients already receiving beta-blockers is unknown. We have assessed the efficacy of oral amiodarone in preventing atrial fibrillation in patients aged 60 years or older undergoing open-heart surgery. METHODS We did a randomised, double-blind placebo-controlled trial in which patients undergoing open-heart surgery (n=220, average age 73 years) received amiodarone (n=120) or placebo (n=100). Patients enrolled less than 5 days before surgery received 6 g of amiodarone or placebo over 6 days beginning on preoperative day 1. Patients enrolled at least 5 days before surgery received 7 g over 10 days beginning on preoperative day 5. FINDINGS Patients on amiodarone had a lower frequency of any atrial fibrillation (22.5% vs 38.0%; p=0.01; absolute difference 15.5% [95% CI 3.4-27.6%]), and there were significant differences in favour of the active drug for symptomatic atrial fibrillation (4.2% vs 18.0%, p=0.001), cerebrovascular accident (1.7% vs 7.0%, p=0.04), and postoperative ventricular tachycardia (1.7% vs 7.0%, p=0.04). Beta-blocker use (87.5% amiodarone vs 91.0% placebo), nausea (26.7% vs 16.0%), 30-day mortality (3.3% vs 4.0%), symptomatic bradycardia (7.5% vs 7.0%), and hypotension (14.2% vs 10.0%) were similar. INTERPRETATION Oral amiodarone prophylaxis in combination with beta-blockers prevents atrial fibrillation and symptomatic fibrillation and reduces the risk of cerebrovascular accidents and ventricular tachycardia.

Mechanisms governing the postural response and baroreceptor abnormalities in chronic congestive heart failure: effects of acute and long-term converting-enzyme inhibition.

We assessed the hemodynamic and hormonal response to tilt and the baroreceptor response in 12 patients in sinus rhythm with severe chronic congestive heart failure. We also assessed the response to acute (n = 12) and chronic (n = 8) converting-enzyme inhibition with captopril. The control tilt was characterized by high cardiac filling pressures, absence of significant peripheral pooling and apparent absence of afferent stimuli for hemodynamic and hormonal response. After acute captopril, the hemodynamic response to tilt was improved, but not normalized. The chronic response was characterized by the absence of a reflex increase of systemic vascular resistance on tilt despite peripheral pooling. Five patients developed orthostatic hypotension, but responded to acute infusion of 0.9% sodium chloride. Efferent sympathetic activity (response to cold pressor) was abnormal during the control study, but indistinguishable from normal subjects by the time of chronic captopril therapy. This paralleled an improved responsiveness of plasma catecholamines during chronic tilt. The Valsalva maneuver remained abnormal. There was a distinct absence of the normally anticipated heart rate increase on tilt, suggesting a parasympathetic abnormality.

Understanding heterogeneity in meta‐analysis: the role of meta‐regression

Background:  Meta‐regression has grown in popularity in recent years, paralleling the increasing numbers of systematic reviews and meta‐analysis published in the biomedical literature. However, many clinicians and decision‐makers may be unfamiliar with the underlying principles and assumptions made within meta‐regression leading to incorrect interpretation of their results.

Cost–Effectiveness of Rivaroxaban Compared to Warfarin for Stroke Prevention in Atrial Fibrillation

Rivaroxaban has been found to be noninferior to warfarin for preventing stroke or systemic embolism in patients with high-risk atrial fibrillation (AF) and is associated with a lower rate of intracranial hemorrhage. To assess the cost-effectiveness of rivaroxaban compared to adjusted-dose warfarin for the prevention of stroke in patients with AF, we built a Markov model using a United States payer/Medicare perspective and a lifetime time horizon. The base-case analysis assumed a cohort of patients with AF 65 years of age with a congestive heart failure, hypertension, age, diabetes, stroke (2 points) score of 3 and no contraindications to anticoagulation. Data sources included the Rivaroxaban Once-daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) and other studies of anticoagulation. Outcome measurements included costs in 2011 United States dollars, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Patients with AF treated with rivaroxaban lived an average of 10.03 QALYs at a lifetime treatment cost of

Therapeutic hypothermia is associated with improved neurologic outcome and survival in cardiac arrest survivors of non-shockable rhythms

94,456. Those receiving warfarin lived an average of 9.81 QALYs and incurred costs of

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)

88,544. The ICER for rivaroxaban was

Neurothrombectomy devices for the treatment of acute ischemic stroke: state of the evidence

27,498 per QALY. These results were most sensitive to changes in the hazard decrease of intracranial hemorrhage and stroke with rivaroxaban, cost of rivaroxaban, and time horizon. Monte Carlo simulation demonstrated rivaroxaban was cost-effective in 80% and 91% of 10,000 iterations at willingness-to-pay thresholds of

Sympathetic responsiveness and plasma norepinephrine during therapy of chronic congestive heart failure with captopril.

50,000 and