Reverse Remodeling Effects of Sacubitril-Valsartan: Structural and Functional Optimization in Stage C Heart Failure

Sacubitril-valsartan, an angiotensin receptor-neprilysin inhibitor, reduces all-cause mortality and the rate of heart failure hospitalizations in patients with heart failure with reduced ejection fraction. This study aimed to elucidate the benefits of initiating sacubitril-valsartan on ventricular remodeling in patients previously optimized on guideline-directed medical therapy. In this prospective, single-arm longitudinal study, 40 patients with heart failure with reduced ejection fraction who were optimized on guideline-directed medical therapy were transitioned to sacubitril-valsartan. The primary end point was the change in left ventricular (LV) volume at 1 year as assessed by 3-dimensional transthoracic echocardiography. Other echocardiographic end points included change in LV-function and change in right ventricular (RV) size and function. The mean age was 55 +/- 12 years, and 63% were male. At 1 year, LV end-diastolic volume decreased from 242 +/- 71 to 157 +/- 57 ml (p <0.001) with a corresponding increase in LV ejection fraction from 32 +/- 7% to 44 +/- 9% (p <0.001). RV end-diastolic volume decreased from 151 +/- 51 to 105 +/- 45 ml (p <0.001). Although RV ejection fraction did not change (51 +/- 8 vs 51 +/- 10; p = 0.35), RV global longitudinal strain improved from -14.9 +/- 3.4 % to -19.3 +/- 4.3% (p <0.001). When added to standard medical therapy for heart failure, sacubitril-valsartan induces significant remodeling of both the right and left ventricles as assessed by 3-dimensional echocardiography.