Prevalence of potential primary aldosteronism in patients with heart failure with reduced ejection fraction: a post hoc analysis of the ALOFT trial

Abstract Background Primary aldosteronism (PA) is a frequently undiagnosed but potentially treatable cause of secondary hypertension, and recent guidelines recommend broader screening using simultaneous measurement of plasma renin activity (PRA) and plasma aldosterone concentration (PAC). Purpose We have examined the application of this screening approach in patients with heart failure with reduced ejection fraction (HFrEF), where some patients may also have renin-independent aldosterone production. Methods In this analysis, we included 278 patients with HFrEF enrolled in the ALOFT (ALiskiren Observation of heart Failure Treatment) trial who had available measurements of both PRA and PAC. The mean age of the cohort was 68±10 years, 78% were male, and the mean LVEF was 31±5%. Biochemical testing was performed without withdrawal of background medical therapy, and PAC was measured using an immunoassay. PA screening results were interpreted using 2 approaches: the 2025 Endocrine Society guideline criteria and a maximally sensitive screening strategy (Table). We also examined the urinary aldosterone excretion threshold of 25 μg/day, said to have high specificity for PA. Results The median PRA was 2.2 ng/mL/h, the median plasma PAC was 8.0 ng/dL, and the median aldosterone-to-renin ratio (ARR) was 3.4 ng/dL per ng/mL/h (Figure). Using the Endocrine Society criteria, 22 of 278 patients (7.9%) screened positive for PA (Table). When the maximally sensitive screening approach was applied, 43 patients (15.5%) were identified as having a positive screening test (Table). The proportion of patients with urinary aldosterone >25 μg/day was 36/276 patients (13.0%). Conclusions Potential renin-independent aldosterone production, meeting the criteria for a positive PA screening test, was identified in a substantial proportion of patients with HFrEF, with estimated prevalence ranging from approximately 7% using recent guideline criteria to over 15% with a maximally sensitive screening approach. Possible renin-independent aldosterone production and its significance should be investigated further in HFrEF (and HFpEF).Distributions of PAC,PRA, and ARRFor image description, please refer to the figure legend and surrounding text.Prevalence of positive screening for PAFor image description, please refer to the figure legend and surrounding text.