Clinical Predictors of Mortality in Patients with Moderate to Severe Mitral Regurgitation.

BACKGROUND: Mitral regurgitation is the most common form of valvular heart disease worldwide, however, there is an incomplete understanding of predictors of mortality in this population. This study sought to identify risk factors of mortality in a real-world population with mitral regurgitation. METHODS: All patients with moderate or severe mitral regurgitation were identified at a single center from January 1, 2016 to August 31, 2017. Multivariate regression was performed to evaluate variables independently associated with all-cause mortality. RESULTS: A total of 490 patients with moderate (76.3%) or severe (23.7%) mitral regurgitation due to primary (20.8%) or secondary (79.2%) etiology were identified. The mean age was 66.7 years; 50% were male. At a median follow-up of 3.1 years, the incidence of all-cause mortality was 30.1%, heart failure hospitalization 23.1%, and mitral valve intervention 11.6%. Of 117 variables, multivariate analysis demonstrated 5 that were independently predictive of mortality: baseline creatinine (hazard ratio [HR] 1.2; 95% CI, 1.0-1.3; P = .02), right atrial pressure by echocardiogram (HR 1.3; 95% CI, 1.07-1.55; P = .008), hemoglobin (HR 0.65; 95% CI, 0.52-0.83; P = .001), hospitalization for heart failure (HR 1.6; 95% CI, 1.1-2.4; P = .015), and mitral valve intervention (HR 0.40; 95% CI, 0.16-0.83; P = .049). CONCLUSION: In this retrospective, pragmatic analysis of patients with moderate or severe mitral regurgitation, admission for heart failure exacerbation, elevated right atrial pressure, renal dysfunction, anemia, and lack of mitral valve intervention were independently associated with increased risk of all-cause mortality. Whether these risk factors may better identify select patients who may benefit from more intensive monitoring or earlier intervention should be considered in future studies.

ESCRT-III is required for scissioning new peroxisomes from the endoplasmic reticulum.

Dynamic control of peroxisome proliferation is integral to the peroxisome's many functions. The endoplasmic reticulum (ER) serves as a source of preperoxisomal vesicles (PPVs) that mature into peroxisomes during de novo peroxisome biogenesis and support growth and division of existing peroxisomes. However, the mechanism of PPV formation and release from the ER remains poorly understood. In this study, we show that endosomal sorting complexes required for transport (ESCRT)-III are required to release PPVs budding from the ER into the cytosol. Absence of ESCRT-III proteins impedes de novo peroxisome formation and results in an aberrant peroxisome population in vivo. Using a cell-free PPV budding assay, we show that ESCRT-III proteins Vps20 and Snf7 are necessary to release PPVs from the ER. ESCRT-III is therefore a positive effector of membrane scission for vesicles budding both away from and toward the cytosol. These findings have important implications for the evolutionary timing of emergence of peroxisomes and the rest of the internal membrane architecture of the eukaryotic cell.