Association between heart failure medical therapy and clinical outcomes after durable left ventricular assist device implantation

Background In patients with heart failure (HF) and reduced left ventricular ejection fraction, guideline-directed medical therapy improves survival. For advanced HF refractory to medical and device therapies, durable left ventricular assist device (LVAD) implantation is indicated. Although LVADs provide substantial left ventricular unloading, preservation of native cardiac function remains important to maintain exercise capacity and quality of life and to prevent aortic regurgitation and right ventricular failure. However, the impact of post-implant HF medical therapy on outcomes has not been well established. Purpose To evaluate the association between HF medical therapy and clinical outcomes after durable LVAD implantation using a nationwide Japanese registry. Methods We analyzed data from the Japanese Registry for Mechanically Assisted Circulatory Support (J-MACS) between June 2010 and December 2025, including consecutive patients undergoing durable LVAD implantation. Patients who died during the index hospitalization were excluded. Associations between discharge prescriptions of ACEi/ARB/ARNI, beta-blockers, and MRA and all-cause death, right ventricular failure, ventricular arrhythmia, and hemocompatibility-related adverse events were assessed using Cox proportional hazards models adjusted for key clinical covariates. The association between the number of HF drug classes and outcomes was also examined. Results A total of 1,623 patients were included (mean age 44.9 ± 14.3 years; 73.3% male). At discharge, ACEi/ARB/ARNI, beta-blockers, and MRA were prescribed in 75.3%, 93.2%, and 72.3%, respectively. Beta-blockers were more frequently used in dilated cardiomyopathy and less in hypertrophic cardiomyopathy, whereas MRA use was more common in hypertrophic cardiomyopathy. Patients receiving ACEi/ARB/ARNI had higher estimated glomerular filtration rates and lower loop diuretic use; beta-blocker users had lower pre-implant left ventricular ejection fraction, and MRA users more frequently required loop diuretics. Post-discharge mortality and right ventricular failure were lower in patients treated with ACEi/ARB/ARNI and beta-blockers, whereas MRA was not associated with these outcomes (Figure 1). No significant associations were observed between any medication class and ventricular arrhythmia or hemocompatibility-related adverse events. The number of HF drug classes was associated with all-cause death and right ventricular failure, but not with ventricular arrhythmia or hemocompatibility-related adverse events (Figure 2). Prescription rates remained stable from discharge to one year after LVAD implantation. Conclusion These findings suggest a potential role for selected HF medical therapies in post-LVAD management; however, causal inference is limited by the observational design. RCTs are warranted to confirm these associations and define the optimal medical therapy strategy after durable LVAD implantation.Figure 1Figure 2