Low- and High-renin Heart Failure Phenotypes with Clinical Implications

Area of Science:

• Cardiology
• Pharmacology
• Biochemistry

Background:

• The renin-angiotensin system (RAS) blockade is a cornerstone therapy for heart failure with reduced ejection fraction (HFrEF).
• The utility of active renin concentration (ARC) in guiding therapy under RAS blockade requires further investigation.
• This study explores angiotensin profiles in HFrEF patients with varying RAS activation levels, as indicated by ARC.

Purpose of the Study:

• To assess angiotensin profiles in HFrEF patients with distinct RAS activations.
• To investigate the effect of different RAS blockade therapy modalities on angiotensin metabolites.
• To determine if ARC can refine HFrEF patient classification beyond NT-proBNP and NYHA stages.

Main Methods:

• Two cohorts of stable chronic HFrEF patients on optimal medical treatment (OMT) were enrolled.
• Active renin concentration (ARC) and angiotensin metabolites (AngI, AngII) were measured using mass spectrometry.
• Patients were categorized into low- and high-renin groups based on ARC screening.

Main Results:

• Concentrations of Angiotensin I (AngI) and Angiotensin II (AngII) strongly correlated with ARC, irrespective of therapy type (ACE-I or ARB).
• Approximately 30% of patients on RAS blockers exhibited lower/normal ARC levels, despite expected upregulation.
• Angiotensin levels were significantly lower in the low-ARC group compared to the high-ARC group.

Conclusions:

• Active renin concentration (ARC) allows for a more nuanced classification of HFrEF patients on OMT.
• ARC identifies distinct neurohumoral HFrEF phenotypes beyond traditional markers like NT-proBNP and NYHA stages.
• This refined classification provides a rationale for tailoring therapeutic interventions in HFrEF management.