Add-on Sacubitril/Valsartan Therapy Induces Left Ventricular Remodeling in Non-responders to Cardiac Resynchronization Therapy to a Similar Extent as in Heart Failure Patients Without Resynchronization.

Abstract

Non-responders to cardiac resynchronization therapy (CRT-NR) have poor prognosis. Sacubitril/valsartan (SV) treatment improved the outcome of patients with heart failure with reduced left ventricular (LV) ejection fraction (HFrEF) in randomized trials with no data on the specific cohort of CRT-NRs. The aim of this study was to compare the echocardiographic and biomarker changes in CRT-NR patients treated with versus without SV, and in patients with HFrEF on SV therapy. CRT-NR patients initiated on SV (groupI), CRT-NR patients on angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) (groupII), and patients with HFrEF (without CRT) initiated on SV (groupIII) were identified in our heart failure (HF) registry. CRT-NR was defined as < 10% improvement in left ventricular ejection fraction (LV EF) 6months after the implantation. Echocardiographic parameters and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at baseline and at the end of follow-up were compared. A total of 275 patients (groupI, 70; groupII, 70; and groupIII, 135) were included. After a follow-up of 7.54 ± 1.8months (mean ± standard deviation [SD]), LV EF (%) increased in groupI (25.2 ± 5.7 versus 29.4% ± 6.7; p < 0.001) and in groupIII (26.6 ± 6.4 versus 29.9 ± 6.7; p < 0.001). LV end-systolic diameters (mm) decreased in groupI (56.6 ± 9.0 versus 54.3 ± 8.7; p = 0.004) and in groupIII (55.9 ± 9.9 versus 54.3 ± 11.2; p = 0.021). The levels of NT-proBNP (pg/mL) decreased in groupI (2058.86 [1041.07-4502.51] versus 1121.55 [545-2541]; p < 0.001) and in groupIII (2223.35 [1233.03-4795.96] versus 1123.09 [500.38-2651.27]; p < 0.001). The extent of improvement was similar in groupsI and III (p > 0.05). No significant changes were detected in groupII. SV therapy induced similar improvements in echocardiographic parameters and in NT-proBNP levels in CRT-NR patients and in patients with HFrEF without resynchronization.