Left Atrial Volume Index and Left Ventricular Mass Index Determine the Benefits of Spironolactone in Patients With Heart Failure With Preserved Ejection Fraction

Clinical Snapshot

Key Findings

• P Value: Significant results: P=0.005 to P=0.045; interaction P=0.029 to P=0.045

• Effect Size: Hazard ratios ranging from 0.26 to 0.63 depending on structural parameter and outcome

• Primary Outcome: Cardiovascular mortality, heart failure hospitalization, and composite endpoint

• Nnt Or Sensitivity: Strongest effect in patients with both increased left atrial volume index and LV mass index (HR 0.31 for CV mortality)

• Confidence Interval: 95% CIs: 0.10-0.98 across different analyses

Clinical Application

Highly feasible - echocardiographic parameters routinely measured, spironolactone readily available and affordable Spironolactone listed on PBS for heart failure; echocardiographic assessment standard in Australian cardiology practice; findings support NHFA-CSANZ guidelines for individualized HFpEF management Australian HFpEF patients with structural heart changes evidenced by increased left atrial volume index or LV mass index on echocardiography

Abstract

BACKGROUND: It is unclear whether patients with heart failure with preserved ejection fraction respond to spironolactone based on cardiac structure or function. METHODS: A post hoc analysis was performed among participants with left ventricular (LV) ejection fraction ≥50% and evidence of abnormal LV diastolic function or filling pressures in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial). Log-rank tests and Cox regression models were used for comparison between groups. RESULTS: Totally, 757 subjects were qualified and stratified by parameters on cardiac structure or function. In patients with increased left atrial volume index, spironolactone reduced cardiovascular mortality (adjusted hazard ratio [HR], 0.48 [95% CI, 0.24-0.98]; P=0.042, log-rank; interaction P=0.045). Meanwhile, in patients with increased LV mass index, spironolactone decreased heart failure hospitalization (adjusted HR, 0.51 [95% CI, 0.32-0.80]; P=0.009, log-rank; interaction P=0.041) and the composite outcome of cardiovascular mortality, heart failure hospitalization, and aborted sudden death (adjusted HR, 0.63 [95% CI, 0.43-0.93]; P=0.045, log-rank; interaction P=0.029). Then, in participants with increased left atrial volume index and LV mass index, who matched at 1:1 ration by propensity score matching, spironolactone reduced cardiovascular mortality (adjusted HR, 0.31 [95% CI, 0.11-0.92]; P=0.039, log-rank), heart failure hospitalization (adjusted HR, 0.26 [95% CI, 0.10-0.68]; P=0.005, log-rank), and the composite outcome (adjusted HR, 0.33 [95% CI, 0.15-0.72]; P=0.006, log-rank). CONCLUSIONS: Spironolactone reduced cardiovascular mortality, heart failure hospitalization, or the composite outcome of cardiovascular mortality, heart failure hospitalization, and aborted sudden death in patients with heart failure with preserved ejection fraction with increased left atrial volume index or LV mass index.

References

1. 1.Zang, H., Jia, C., Pan, Y., Li, X., & Zhang, Q. (2026). Left Atrial Volume Index and Left Ventricular Mass Index Determine the Benefits of Spironolactone in Patients With Heart Failure With Preserved Ejection Fraction. Journal of the American Heart Association, Article 044115. https://doi.org/10.1161/JAHA.125.044115