Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

A comparison of acoustic cardiography and echocardiography for optimizing pacemaker settings in cardiac resynchronization therapy

BACKGROUND: Cardiac resynchronization therapy (CRT) is useful in managing patients with refractory heart failure. To increase efficacy, pacemaker settings are optimized, with Doppler echocardiography being the preferred method. Recently, acoustic cardiography, an automated method that records, analyzes, and displays simultaneous ECG and heart sound data, has been developed. In this study, the suitability of acoustic cardiography as an alternative to Doppler echocardiography in CRT optimization is evaluated. METHODS: We studied 43 CRT patients undergoing optimization. Using Doppler echocardiography, we determined the optimal atrioventricular (AV) delay with a transmitral flow assessment. For optimization of the interventricular (VV) delay, we used the left ventricular outflow tract velocity time integral (VTI). For acoustic cardiography, we used the electromechanical activation time (EMAT, the interval from QRS onset to the S1). Reproducibility of echocardiography and acoustic cardiography was determined by programming 10 different delay settings twice in random order. RESULTS: All 43 subjects underwent AV optimization, and 14 had CRT devices allowing VV optimization. While the intraobserver variability of EMAT and Doppler echocardiography parameter was similar (9.9% vs 8.5%), the reproducibility of EMAT was the highest (r = 0.91) and VTI was the lowest (r = 0.35). The correlation between the optimal AV delays determined by EMAT versus transmitral flow assessment was 0.86 (P > 0.001). The correlation between the optimal VV delays determined by EMAT versus VTI was 0.58 (P > 0.05), perhaps due to the poor reproducibility of the VTI. CONCLUSION: For CRT optimization, acoustic cardiography provides results similar to echocardiography but with improved reproducibility and ease of use

The correlation between presenting ST-segment depression and the final size of acute myocardial infarcts in patients with acute coronary syndromes

The use of reperfusion therapy in patients with ST elevation acute coronary syndromes had been established. However, reperfusion therapy is usually considered contra-indicated in those with ST depression, despite the knowledge that regional posterior infarction is typically indicated by ST depression maximal in leads V 1 to V 3 and nonregional subendocardial infarction is typically indicated by marked ST depression maximal in other leads. This study of patients with non-ST-elevation acute coronary syndromes investigates the quantitative relationship between presenting ST depression and final QRS changes in both of these subgroups. The final QRS score was significantly higher (2.44 points) than that of a control group with not ST depression, (1.55 points) in the group with maximal ST depression in V 1 to V 3 ( P=0.04). However, in the entire population, there was a highly significant correlation ( P=.003) between the sum of the presenting ST depression and the final QRS score. Trials of reperfusion therapy will be required to determine if such evolution to electrocardiogram documented acute myocardial infarction can be prevented in patient with marked ST depression acute coronary syndromes