Isovolumic Contraction Velocity in Heart Failure With Reduced Ejection Fraction and Effect of Sacubitril/Valsartan: the PROVE-HF Study

Abstract

To assess tissue Doppler-derived mitral annular isovolumic contraction velocity (ICV) after starting sacubitril/valsartan (sac/val) for the treatment of heart failure with reduced ejection fraction (HFrEF; left ventricular [LV] EF <40%). ICV may inform load-independent systolic function; combining ICV and LVEF may improve assessment of LV contractility. Among 651 HFrEF participants treated with sac/val, echocardiograms were performed at baseline, 6, and 12 months. Pre-treatment median ICV and LVEF were used for classification to predict LV reverse remodeling, health status using the Kansas City Cardiomyopathy Questionnaire, and biomarker concentrations. The mean age was 64.6±12.4 years, and 28% were women, baseline LVEF: 28.9±6.9%. Compared to baseline, median ICV increased post sac/val therapy (4.6 [3.5, 6.1] vs. 4.9 [3.6, 6.4], p=0.005). ICV added value to separate and combined models of biomarkers, clinical, and echocardiographic variables for prediction of post-therapy EF recovery. Classification using baseline ICV/EF yielded relatively equal numbers in 4 groups based on low/high ICV or LVEF. Most deleterious results for remodeling, health status, and biomarkers were found in low-ICV/low-EF patients, while high ICV/high EF had the best profiles; other groups were intermediate. Significant shifts towards better ICV/EF profiles were noted post sac/val treatment compared to baseline, with doubling of high-ICV/high-EF [241(60%) vs. 123(31%)] and 78% reduction of low-ICV/low-EF [28(7%) vs. 125(32%)]. In HFrEF, ICV adds to the profiling of systolic function and represents an independent predictor of reverse cardiac remodeling after treatment with sac/val. ICV changes may be used for assessment of treatment response.