Insights into the renin–angiotensin–aldosterone system in transthyretin amyloid cardiomyopathy

AIM: This study aimed to characterize circulating renin-angiotensin-aldosterone system (RAAS) patterns in transthyretin amyloid cardiomyopathy (ATTR-CM), examine their relationship with clinical and echocardiographic parameters and determine their prognostic value. METHODS: In this prospective study, ATTR-CM patients underwent serum quantification of classical (angiotensin I-IV, aldosterone) and alternative (angiotensin 1-7, angiotensin 1-5) RAAS peptides and angiotensin converting enzyme 2 (ACE2) activity using mass spectrometry. RAAS inhibitor use was recorded. Associations of RAAS peptides with N-terminal pro brain natriuretic peptide (NT-proBNP) and echocardiographic parameters were analyzed. Prognostic associations with the composite endpoint of HF hospitalization or cardiac death were assessed using Kaplan-Meier curves stratified by median peptide values. RESULTS: Among 137 patients, RAAS inhibitor use included ACEi (21.2%), ARBs (34.3%), ARNIs (7.3%) and none (26.0%). RAAS profiles were consistent with the expected effects of the respective RAAS inhibitors. During a median follow-up of 1.6 years, 49 patients (36%) experienced the composite endpoint. Patients with adverse cardiac events had higher ACE2 activity (p