Estimated Plasma Volume Status May Modify the Association between Estimated Glomerular Filtration Rate and Atrial Fibrillation in Heart Failure with Preserved Ejection Fraction: A post hoc Analysis of the TOPCAT Trial.

Abstract

Introduction: This post hoc analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial examined whether estimated plasma volume status (ePVS) modifies the association between estimated glomerular filtration rate (eGFR) and incident atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF).

Methods: A total of 2,202 HFpEF patients without baseline AF were included. ePVS was calculated using the Duarte formula, and participants were stratified into low and high ePVS groups based on the cohort median. Multivariable Cox proportional hazards models were used to assess the association between eGFR and incident AF, with stratified analyses by spironolactone treatment.

Results: During follow-up, 4.9% of patients developed incident AF. No significant association between eGFR and AF was observed in the low ePVS group. In contrast, among patients with high ePVS, higher eGFR was associated with a reduced risk of incident AF after multivariable adjustment, with a significant nonlinear relationship (p for nonlinearity <0.001) and a statistically significant eGFR × ePVS interaction (p for interaction = 0.010). The association was consistent regardless of spironolactone use.

Conclusion: This exploratory post hoc analysis suggested that ePVS may modify the association between eGFR and incident AF in HFpEF, with lower eGFR linked to higher AF risk primarily in patients with elevated ePVS. These hypothesis-generating findings should be interpreted cautiously given the limited number of events. Prospective studies are warranted to validate this potential interaction and its clinical implications.