Prevalence and Prognostic Significance of Mitral Regurgitation in Acute Decompensated Heart Failure: The ARIC Study

Objectives: This study investigates the prevalence and prognostic significance of mitral regurgitation (MR) in acute decompensated heart failure (ADHF) patients. Background: Few studies characterize the burden of MR in heart failure. Methods: The ARIC (Atherosclerosis Risk In Communities) study surveilled ADHF hospitalizations for residents ≥55 years of age in 4 U.S. communities. ADHF cases were stratified by left ventricular ejection fraction (LVEF): <50% and ≥50%. Odds of moderate or severe MR in patients with varying sex and race, and odds of 1-year mortality in those with higher MR severity were estimated using multivariable logistic regression. Results: From 2005 to 2014, there were 17,931 weighted ADHF hospitalizations of which 49.2% had an LVEF <50% and 50.8% an LVEF ≥50%. Moderate or severe MR prevalence was 44.5% in those with an LVEF <50% and 27.5% in those with an LVEF ≥50%. Moderate or severe MR was more likely in females than males regardless of LVEF; LVEF <50% (odds ratio [OR]: 1.21 [95% confidence interval (CI): 1.11 to 1.33]), LVEF ≥50% (OR: 1.52 [95% CI: 1.36 to 1.69]). Among hospitalizations with an LVEF ≥50%, moderate or severe MR was less likely in blacks than whites (OR: 0.72 [95% CI: 0.64 to 0.82]). Higher MR severity was independently associated with increased 1-year mortality in those with an LVEF <50% (OR: 1.30 [95% CI: 1.16 to 1.45]). Conclusions: Patients with ADHF have a significant MR burden that varies with sex and race. In ADHF patients with an LVEF <50%, higher MR severity is associated with excess 1-year mortality

Epidemiology and Outcomes of Aortic Stenosis in Acute Decompensated Heart Failure: The ARIC Study

Background: Few studies characterize the epidemiology and outcomes of aortic stenosis (AS) in acute decompensated heart failure (ADHF). This study investigates the significance of AS in contemporary patients who have experienced an ADHF hospitalization. Methods: The ARIC study (Atherosclerosis Risk in Communities) surveilled ADHF hospitalizations for residents ≥55 years of age in 4 US communities. ADHF cases were stratified by left ventricular ejection fraction (LVEF). Demographic differences in AS burden and the association of varying AS severities with mortality were estimated using multivariable logistic regression. Results: From 2005 through 2014, there were 3597 (weighted n=16 692) ADHF hospitalizations of which 48.6% had an LVEF <50% and 51.4% an LVEF ≥50%. AS prevalence was 12.1% and 18.7% in those with an LVEF <50% and ≥50%, respectively. AS was less likely in Black than White patients regardless of LVEF: LVEF <50% (odds ratio [OR], 0.34 [95% CI, 0.28-0.42]); LVEF ≥50% (OR, 0.51 [95% CI, 0.44-0.59]). Higher AS severity was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.16 [95% CI, 1.04-1.28]); LVEF ≥50% (OR, 1.40 [95% CI, 1.28-1.54]). Sensitivity analyses excluding severe AS patients detected that mild/moderate AS was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.23 [95% CI, 1.02-1.47]); LVEF ≥50% (OR, 1.31 [95% CI, 1.14-1.51]). Conclusions: Among patients who have experienced an ADHF hospitalization, AS is prevalent and portends poor mortality outcomes. Notably, mild/moderate AS is independently associated with 1-year mortality in this high-risk population

Expression of Runx2/Cbfa1/Pebp2aA during angiogenesis in postnatal rodent and fetal human orofacial tissues

Transient expression of Runx2 is reported in endothelial cells and vascular smooth muscle cells during vessel formation in skin, stroma of forming bones and developing periodontal ligament, developing skeletal muscle cells, and fat tissue. The data suggest that Runx2 is expressed in a multipotential mesenchymal cell population that gives rise to various osseous and nonosseous cell lineages. Runx2/Cbfa1 is a transcription factor essential for cells of osteogenic and dentinogenic lineages. Here we examined expression of Runx2/Cbfa1 (all isotypes) in several nonskeletal cell types present in developing orofacial tissues of neonatal rodents and human fetuses with special emphasis on vessel formation. Sections obtained from heads or jaws of postnatal mice, hamster, and human fetuses were immunostained with monoclonal anti-Pebp2aA antibody. Mouse and human tissues were also examined by in situ hybridization. Sections of Runx2 null mutant mice with a LacZ reporter construct inserted in the Runx2 locus were stained for Runx2 promoter activity with anti-galactosidase. We found transient mRNA and protein expression in endothelial cells and in vascular smooth muscle cells of forming vessels in skin, alveoli of forming bone, and forming periodontal ligament. We also noticed weak and variable expression in some fibroblasts of embryonic skin, early differentiating cross-striated muscle cells, and differentiating fat cells. Runx2 is not an exclusive marker for chondrogenic, osteogenic, and dentinogenic tissues, but is much more widely present in an early multipotential mesenchymal cell population that gives rise to several other lineage

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 sPLA2 inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2 inhibition 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 measure was 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 sPLA2 inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246.Stephen J. Nicholls, John J. P. Kastelein, Gregory G. Schwartz, Dianna Bash, Robert S. Rosenson, Matthew A. Cavender, Danielle M. Brennan, Wolfgang Koenig, J.Wouter Jukema, Vijay Nambi, R. ScottWright, Venu Menon, A. Michael Lincoff, Steven E. Nissen for the VISTA-16 Investigator