Renin-Angiotensin-Aldosterone System Activation and Diuretic Response in Ambulatory Heart Failure Patients

Abstract

Rationale & Objective

Heart failure treatment relies upon loop diuretics to induce natriuresis and decongestion, but therapy is often limited by diuretic resistance. We explored the association of renin-angiotensin-aldosterone system (RAAS) activation with diuretic response.

Study Design

Observational cohort.

Setting & Population

Euvolemic ambulatory adults with chronic heart failure were administered torsemide in a monitored environment.

Predictors

Plasma total renin, active renin, angiotensinogen and aldosterone. Urine total renin and angiotensinogen.

Outcomes

Sodium output per doubling of diuretic dose (Na-DE) and fractional excretion of sodium per doubling of diuretic dose (FENa-DE).

Analytical Approach

Robust linear regression models estimated associations of each RAAS intermediate with outcomes.

Results

Analysis included 56 participants, with median age 65 years; 50% female; 41% Black. Median home diuretic dose was 80 mg furosemide equivalents. In unadjusted and multivariable adjusted models, higher levels of RAAS measures were generally associated with lower diuretic efficiency (DE). Higher plasma total renin remained significantly associated with lower Na-DE (ß=-0.41 [-0.76, -0.059] per SD change) with adjustment; higher plasma total and active renin were significantly associated with lower FENa-DE (ß=-0.48 [-0.83, -0.14] and ß=-0.51 [-0.95, -0.08], respectively) in adjusted models. Stratification by RAAS inhibitor use did not substantially alter these associations.

Limitations

Small sample size; highly-selected participants; associations may not be causal.

Conclusions

Among multiple measures of RAAS activation, higher plasma total and active renin were consistently associated with lower diuretic response. These findings highlight potential drivers of diuretic resistance and underscore the need for high-quality trials of decongestive therapy enhanced by RAAS blockade.