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. While prospective randomized controlled trials (RCTs) have not investigated the use of HF therapies in LVAD recipients, observational data suggest benefits of neurohormonal blockers, especially in achieving blood pressure (BP) targets associated with improved outcomes. METHODS: ENVAD-HF is an investigator-initiated prospective multicenter, randomized, open-label, parallel group, pilot study in HeartMate 3 (HM3) LVAD recipients to evaluate the safety and tolerability and insights on efficacy of sacubitril/valsartan compared to standard of care (SOC) for managing BP. Medically stable LVAD recipients 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 (MAP) goal 75-90 mmHg over a 12-month follow-up. The primary endpoint, designed to assess the safety and efficacy of sacubitril/valsartan compared to 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% females, mean age 57±12 years, 67% in ambulatory follow-up, 55% ischemic etiology, 25% receiving an LVAD as destination therapy, with mean baseline MAP 87±7 mmHg and median NTproBNP 2552 (1595-3543] pg/mL. CONCLUSION: ENVAD-HF is the first prospective RCT of pharmacological therapy for management of BP in stable HM3 LVAD recipients achieving target enrolment. It will provide data on safety, tolerability and insights on efficacy of sacubitril/valsartan versus SOC used for treating BP.

Brigham and Women's Hospital Harvard Medical School Boston Massachusetts USA

Cardiovascular Institute Thorax Center Department of Cardiology Erasmus Medical Centre Rotterdam The Netherlands

Department of Cardiac and Transplant Surgery Dubrava University Hospital Zagreb Croatia

Department of Cardiac and Vascular Diseases Jagiellonian University Medical College Institute of Cardiology; John Paul 2 Hospital Krakow Poland

Department of Cardiology Division of Heart and Lungs University Medical Centre Utrecht University of Utrecht the Netherlands

Department of Cardiology University Hospital of Zurich Zurich Switzerland

Department of Cardiovascular Diseases University of Zagreb School of Medicine University Hospital Centre Zagreb Zagreb Croatia

Division of Cardiology Montefiore Health System Bronx New York USA

Institute for Clinical and Experimental Medicine Prague Czech Republic

Seymour Paul and Gloria Milstein Division of Cardiology Department of Medicine Columbia University Irving Medical Center NewYork Presbyterian Hospital New York USA

University of Zagreb School of Medicine Zagreb Croatia

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