Poorer exercise accommodation of regional systolic myocardial motion after spironolactone treatment in heart failure patients with preserved ejection fraction and ventricular dyssynchrony

Patients with heart failure and preserved ejection fraction (HFpEF) are known to have reduced systolic myocardial velocity (Sm) with impaired accommodation to exercise. We tested the impact of an aldosterone antagonist on Sm at rest and post-exercise. Forty-nine HFpEF patients (65 ± 11 years, 24 male) with HF signs/symptoms, mitral E/Ea (annular early diastolic velocity) > 8, and left ventricular (LV) EF > 50% were randomized to spironolactone (25 mg/day, 25 patients) or the Control. At baseline and 6 months, we analyzed Sm of basal LV segments at rest and after a 6 min treadmill exercise. At 6 months, post-exercise mean Sm in the spironolactone group became greater than that in the Control (9.2 ± 1.6 vs. 8.3 ± 1.0 cm/s, p = 0.021), mainly due to the increment of post-exercise % increase of lateral Sm (44 ± 30 vs. 30 ± 19% at baseline, p = 0.045). Further analyses showed the presence of systolic dyssynchrony (standard deviation of electromechanical delay of 6-basal LV segments > 35 ms) was independently associated with a poorer response to spironolactone, defined as a post-exercise % increase of lateral Sm<50% (OR = 2.7, 95% CI = 1.8–4.2) and the increment of Ea < 1.5 cm/s (OR = 1.5, 95% CI = 1.1–2.3). Spironolactone could improve exercise accommodation of regional systolic myocardial velocity for HFpEF patients. However, its benefits could be decreased in those with ventricular dyssynchrony. This suggested possible therapeutic impacts from underlying heterogeneity within HFpEF patients.