Rationale, design, and baseline characteristics of the multicENter, randomized, open-label, parallel group, study to evaluate the use of sacubitril/valsartan in HeartMate 3 left ventricular assist device recipients (ENVAD-HF).

Abstract

Background: With notable improvements in long-term survival and hemocompatibility-related events, heart failure (HF) is emerging as a leading cause of death in the contemporary left ventricular assist device (LVAD) population. Although prospective randomized controlled trials have not investigated the use of HF therapies in recipients of LVAD, observational data suggest benefits of neurohormonal blockers, especially in achieving blood pressure (BP) targets associated with improved outcomes.

Methods: The study "multicENter, randomized, open-label, parallel group, pilot study to evaluate the use of sacubitril/valsartan in HeartMate 3 LVAD recipients" (ENVAD-HF) is an investigator-initiated prospective multicenter, randomized, open-label, parallel group, pilot study of recipients of HeartMate 3 (HM3) LVADs to evaluate the safety and tolerability and insights on efficacy of sacubitril/valsartan compared to standard of care (SOC) for managing BP. Medically stable recipients of LVADs after a recent HM3 implantation or in ambulatory follow-up were eligible for participation and randomized 1:1 to receive sacubitril/valsartan or SOC used for treating BP, both titrated aiming for a mean arterial pressure goal 75-90 mm Hg over a 12-month follow-up. The primary endpoint, designed to assess the safety and efficacy of sacubitril/valsartan compared with SOC, is a composite of freedom from all-cause death, deterioration in renal function, hyperkalemia, or symptomatic hypotension. The occurrence of the primary endpoint will be assessed in the first three months and during the overall duration of the trial (12 months). Other endpoints include clinical and patient-reported outcomes, biomarker, and echocardiography assessments during follow-up.

Results: ENVAD-HF enrolled 60 patients between February 2021 and March 2024: 17% were female, mean age was 57 ± 12 years, 67% were in ambulatory follow-up, 55% had ischemic etiology, and 25% were receiving an LVAD as destination therapy, with mean baseline mean arterial pressure 87 ± 7 mm Hg and median N-terminal pro B-type natriuretic peptide 2552 (1595-3543) pg/mL.

Conclusion: ENVAD-HF is the first prospective randomized controlled trial of pharmacologic therapy for the management of BP in stable recipients with HM3 LVADs achieving target enrollment. It will provide data on safety, tolerability, and insights on efficacy of sacubitril/valsartan versus SOC used for treating BP.