Aldosterone Blockade in Diastolic Heart Failure

Study Questions:

Does aldosterone blockade improve exercise capacity in diastolic heart failure patients who demonstrate exercise-induced elevations in left ventricular (LV) filling pressure?

Methods:

The STRUCTURE (SpironolacTone in myocaRdial dysfUnCTion with redUced exeRcisE capacity) trial was a randomized, blinded, controlled trial, which enrolled 150 diastolic heart failure patients due to nonischemic cardiomyopathy (age 67 ± 9 years) with exertional shortness of breath (New York Heart Association class II-III and exertional E/e’ >13 mm Hg). The patients were randomized to 6 months of placebo or 25 mg/day of spironolactone therapy. Peak VO2 and exertional E/e’ ratio were primary outcomes, and improvements in exercise blood pressure response and global LV longitudinal strain (GLS) were secondary outcomes.

Results:

A total of 131 patients completed therapy at the end of the follow up period—64 on spironolactone and 67 on placebo (120 mg/d of microcellulose). Predicted peak VO2 was 64 ± 17% at baseline. In the spironolactone group, exercise capacity improved significantly (increment in peak VO2 [2.9 (95% CI, 1.9-3.9) vs. 0.3 (95% CI, -0.5 to 1.1) ml/min/kg; p < 0.001], anaerobic threshold [2.0 (95% CI, 0.9-3.2) vs. -0.9 (95% CI, -3.4 to 1.6) ml/min/kg; p = 0.03], O2 uptake efficiency [0.19 (95% CI, 0.06-0.31) vs. -0.07 (95% CI, -0.17 to 0.04); p = 0.002]) with reduction in exercise-induced increase in E/e’ (-3.0 [95% CI, -3.9 to -2.0] vs. 0.5 [95% CI, -0.6 to 1.6]; p < 0.001). There was a significant interaction of spironolactone and change in E/e’ on VO2 (p = 0.039). The spironolactone arm also showed favorable changes in metabolic equivalents, exercise time, and respiratory exchange ratio at follow-up. There was no improvement in GLS.

Conclusions:

The study authors concluded that in diastolic heart failure, spironolactone therapy has a beneficial effect on exercise capacity.

Perspective:

Given that there is no definitive therapy for diastolic heart failure patients, this study with a modest sample size is important because it suggests that spironolactone may be beneficial in a subset of patients who have increased LV filling pressure due to exertion. Studies with larger sample sizes are needed to validate these findings.

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Chronic Heart Failure, Exercise

Keywords: Aldosterone, Anaerobic Threshold, Blood Pressure, Cardiomyopathies, Diuretics, Dyspnea, Exercise Tolerance, Exercise, Heart Failure, Heart Failure, Diastolic, Metabolic Equivalent, Mineralocorticoid Receptor Antagonists, Physical Exertion, Spironolactone, Stroke Volume


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