Authors:

C Ferreira¹ , AS Martinho¹ , JP Almeida¹ , AZ Freitas¹ , JA Ferreira¹ , C Domingues¹ , J Milner¹ , S Costa¹ , F Franco¹ , H Vieira¹ , R Coutinho¹ , R Baptista¹ , L Goncalves¹ , ¹University Hospitals of Coimbra, Cardiology A - Coimbra - Portugal ,

Citation:

BACKGROUND AND PURPOSE:The addition of Angiotensin Receptor-Neprilysin Inhibitors (ARNI) to standard therapy of heart failure with reduced ejection fraction (HFrEF) has proved to improve outcomes. Cardiopulmonary exercise testing (CPET)-derived ergometric variables, as peak oxygen consumption (VO2), are used to determine heart transplant (HTx) eligibility. We aimed to analyse the impact of ARNI therapy in CPET variables.

METHODS: We conducted a retrospective, observational cohort study, including 19 patients with symptomatic HFrEF with a left ventricular (LV) ejection fraction (LVEF) <35% and whose functional capacity was evaluated by CPET less than 6 months before initiating ARNI. We excluded patients who had implanted a cardiac resynchronization therapy device (CRT) or were submitted to heart surgery less than 6 months before the first CPET. A follow-up CPET was conducted 7±4 months after starting ARNI. 

RESULTS: Mean age was 55±12 years and 90% were male.Mean LVEF was 26±6% and before initiating ARNI, all patients were on optimal medical therapy, including angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (100%), ß-blockers (94.7%) and mineralocorticoid receptor antagonists (89.5%). Moreover, 9 patients had an implantable cardioverter defibrillator (D) and 9 patients had a CRT-D.Regarding aetiology, 11 had ischemic heart disease, 6 had dilated cardiomyopathy, 1 had corrected transposition of great arteries and 1 had LV non-compaction. The majority of the patients (73.7%) were on maximal doses of ARNI (97/103mg bid); the remaining were on intermediate dose (49/51 bid). Following ARNI, peak VO2significantly increased from 15.4±5.2 to 17.0±4.0 mL.kg-1.min-1(mean absolute increase of +1.5 mL.kg-1.min-1, p=0.03). Among the 7 patients with peak VO2<14 mL.kg-1.min-1, 3 (43%) improved peak VO2to values >14 mL.kg-1.min-1, pulling the patients out of one of the classical HTx eligibility markers. Regarding other ergometric variables, a numerically increase was observed in mean total exercise duration (12:45 to 13:27 min), in respiratory exchange ratio (RER) (1.08±0.11 to 1.12±0.08) and in peak oxygen pulse (9.9±2.7 to 10.6±2.6 mL.beat-1). Conversely, the mean respiratory efficiency index (VE/VCO2) following ARNI remained similar. 

CONCLUSION: In this cohortof HFrEF patients, ARNI significantly improved peak VO2, a major prognostic predictor. Importantly, 3 out of 7 patients with a peak VO2within the HTx threshold recovered to ineligibility values.