Memory of the renin-angiotensin system following heart transplantation or implantation of a left ventricular assist device

Abstract Background Renin-angiotensin system (RAS) inhibitors, while not routinely recommended after heart transplantation (HT), are advised in left ventricular assist device (LVAD) recipients to promote reverse remodeling and support myocardial recovery. Whether restoring hemodynamics through HT or LVAD implantation sufficiently resolves neurohormonal activation remains uncertain. Methods Patients with end-stage heart failure undergoing HT or LVAD implantation were enrolled in a prospective registry. NT-proBNP, plasma active renin concentration (ARC), aldosterone levels, and the complete profile of angiotensin metabolites were assessed before and after the intervention in 49 HT and 12 LVAD recipients. Results The use of RAS inhibitors was significantly reduced after HT ( p < 0.001) and remained comparable in LVAD patients ( p = 0.453). Both HT and LVAD were associated with reductions in NTproBNP (3015 to 1140 pg/mL; p < 0.001; 8980 to 1836 pg/mL; p = 0.002) and ARC levels (278 to 87µIU/mL; p < 0.001; 847 to 131 µIU/mL; p = 0.074), which was accompanied by a decrease in the angiotensin burden of the classical RAS axis (AngI + AngII: 159 to 47 ng/L, p < 0.001; 214 to 42 ng/L, p = 0.155). However, no patient showed normalization of NT-proBNP levels. Additionally, plasma renin remained elevated in 76% of HT and 67% of LVAD recipients, accompanied by detectable Ang II levels. Conclusion Continuing AngII spill-over after HT and LVAD may affect patient outcomes, potentially contributing to complications. The findings support the rationale for cardioprotective treatment, particularly with RAS inhibitors, in most patients, while further studies should address the long-term effect of this strategy. Graphical Abstract HT—heart transplantation, RAS—renin-angiotensin system, LVAD—left ventricular assist device. Created with BioRender.com (License by the Medical University of Vienna)