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Background: Left ventricular assist devices (LVADs) are underused among women with advanced heart failure, but reasons remain unclear. Outcomes in women compared with men with contemporary fully magnetically levitated LVADs remain uncertain., Objectives: The authors examined differences in characteristics, 2-year outcomes, and risk for key adverse events among women and men., Methods: In 2,200 HeartMate3 (HM3) (Abbott Cardiovascular) LVAD recipients in the MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3), survival free of disabling stroke or reoperation to replace or remove a malfunctioning pump at 2 years was analyzed between women and men. Other outcomes included overall 2-year survival, adverse events, and functional measures., Results: Women comprised 20.4% (n = 448 of 2,200) of the study population and were younger, with nonischemic cardiomyopathy, and more often were Black persons compared with men. The primary endpoint (women 79.4% vs men 75.5% (adjusted [a]HR: 0.96 [95% CI: 0.75-1.24]; P = 0.66) or survival at 2 years (women 82.4% vs men 80.2%; aHR: 1.06 [95% CI: 0.81-1.40]; P = 0.66) was no different. Women had an increased rate of stroke (adjusted incidence rate ratio [aIRR]: 1.52 [95% CI: 1.09-2.11]; P = 0.012), major bleeding (aIRR: 1.28 [95% CI: 1.15-1.42]; P < 0.0001) and infection (aIRR 1.14 [95% CI: 1.03-1.55]; P = 0.01), but these differences were not seen among older (>65 years) patients. Both groups had similar gains in 6-minute walk distance and quality-of-life measurements., Conclusions: There were no differences in the primary composite endpoint or overall survival in women compared with men at 2 years of support. Reasons underlying increase in hemocompatibility-related events and infection-related morbidity in younger women deserves further study. (MOMENTUM 3 IDE [HM3], NCT02224755; MOMENTUM 3 Continued Access Protocol [MOMENTUM 3 CAP], NCT02892955)., Competing Interests: Funding Support and Author Disclosures Both MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) IDE (Investigational Device Exemption) and CAP (Continued Access Protocol) studies were sponsored by Abbott. Dr Cogswell has served on Speakers Bureau and as an advisory board member for Abbott and Medtronic; her spouse is an employee of Medtronic. Dr Ravichandran has served on Speakers Bureau for Abbott and Medtronic. Dr Cleveland has served as an advisory board member for Abbott and Medtronic. Dr Mehra has received consulting fees from Abbott, paid to Brigham and Women’s Hospital; has served as steering committee member for Medtronic and Janssen (Johnson and Johnson); has served on the data and safety monitoring board for Mesoblast; has served as a consultant for Natera, Paragonix, Transmedics, Moderna, Baim Institute of Clinical Research, and Broadview Ventures; and has served as a scientific board member for NuPulseCV, Leviticus, and FineHeart. Dr Goldstein has served as a consultant and as an advisory board member for Abbott and Abiomed. Dr Uriel is on the medical advisory board for Livemetric, Revamp, and Leviticus; and has received grants from Abbott, Abiomed, and Fire. Nicholas Dirckx and Dr Ahmed are employed by Abbott. Dr Yuzefpolskaya has served on Speakers Bureau for Abbott; and has received an educational grant from Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Heart failure (HF) is the leading cause of hospital admissions in the United States in people over the age of 65 years. Major advancements in the medical therapy of HF, combined with automatic implantable cardioverter-defibrillators and cardiac resynchronization therapy, have substantially reduced the mortality and morbidity of chronic HF, but mortality remains high, and the availability of donor hearts for transplantation is limited. Thus, there has been and continues to be a need for alternative therapies to support the failing heart. The development of mechanical pumps designed to assist or replace cardiac function started three decades ago with the National Heart, Lung, and Blood Institute's request for proposals to develop an artificial heart. Significant progress has been made, with ventricular assist devices evolving from bulky extracorporeal devices to internalized miniaturized devices. Improvements in durability, thrombogenicity, ease of implantation, and patient selection have allowed expanding indications for these devices.

Background: Heart failure is associated with reversal to a fetal gene expression pattern of contractile and metabolic genes. Substantial recovery of ventricular function with assist devices is rare. Our goal was to evaluate the effects of assist devices on fetal gene expression and hypoxia inducible factor-1 alpha (HIF-1 alpha), a transcriptional factor in hypoxic signaling., Methods: Human heart tissue was obtained from the left ventricular apex at the time of assist device implantation and again from the left ventricular free wall during cardiac transplantation. Non-failing tissue was obtained from unused hearts from human donors. Gene expression was measured with the Affymetrix 133 plus 2 Array. HIF-1 alpha was measured by Western blotting with commercially available antibodies., Results: Heart failure was associated with a decrease in alpha-myosin heavy chain and sarcoplasmic reticulum-Ca(2+) adenosine triphosphatase messenger RNA expression along with an increase in skeletal tropomyosin. This pattern persisted after assist device therapy. Heart failure was also associated with abnormalities in regulatory metabolic genes including glucose transporter 1 (GLUT1). These patterns also persisted after assist device therapy despite a reduction in atrial natriuretic peptide expression and normalization of HIF-1 alpha., Conclusions: Failure of assist devices to produce sustained recovery of myocardial contractile function may be due in part to persistent fetal transcriptional patterns of contractile and metabolic genes.