Interplay of sex hormones and long-term right ventricular adaptation in a Dutch PAH-cohort

J van Wezenbeek, JA Groeneveldt, A Llucià Valldeperas, CEE van der Bruggen, SMA Jansen, AJ Smits, Rowan Smal, Joost W. van Leeuwen, Cris dos Remedios, A. Keogh, Marc Humbert, Peter Dorfmuller, Olaf Mercier, Christophe Guignabert, JWM Niessen, ML Handoko, JT Marcus, LJ Meijboom, F.P.T. Oosterveer, BE WesterhofAC Heijboer, HJ Bogaard, A Vonk-Noordegraaf, Marie-José T. H. Goumans, FS de Man*

*Corresponding author for this work

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: To investigate the association between altered sex hormone expression and long-term right ventricular (RV) adaptation and progression of right heart failure in a Dutch cohort of Pulmonary Arterial Hypertension (PAH)-patients across a wide range of ages.
: In this study we included 279 PAH-patients, of which 169 females and 110 males. From 59 patients and 21 controls we collected plasma samples for sex hormone analysis. Right heart catheterization (RHC) and/or cardiac magnetic resonance (CMR) imaging was performed at baseline. For longitudinal data analysis we selected patients that underwent a RHC and/or CMR maximally 1.5 years prior to an event (death or transplantation, N=49).
: Dehydroepiandrosterone-sulfate (DHEA-S) levels were reduced in male and female PAH-patients compared to controls, whereas androstenedione and testosterone were only reduced in female patients. Interestingly, low DHEA-S and high testosterone levels were correlated to worse RV function in male patients only. Subsequently, we analyzed prognosis and RV adaptation in females stratified by age. Females≤45years had best prognosis in comparison to females≥55years and males. No differences in RV function at baseline were observed, despite higher pressure-overload in females≤45years. Longitudinal data demonstrated a clear distinction in RV adaptation. Although females≤45years had an event at a later time point, RV function was more impaired at end-stage disease.
: Sex hormones are differently associated with RV function in male and female PAH-patients. DHEA-S appeared to be lower in male and female PAH-patients. Females≤45years could persevere pressure-overload for a longer time, but had a more severe RV phenotype at end-stage disease.
Original languageEnglish
JournalJournal of Heart and Lung Transplantation
Publication statusAccepted/In press - 14 Nov 2021

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