Benefits of diastolic function improvement in heart failure questioned

By Caroline Price, Senior medwireNews Reporter

The importance of left ventricular (LV) diastolic function improvement in patients with heart failure (HF) with preserved ejection fraction (EF) has been questioned, after researchers found that treatment with spironolactone resulted in some functional improvements but failed to impact on patients' exercise capacity.

Burkert Pieske (Medical University Graz, Austria) and colleagues report in JAMA that long-term aldosterone blockade with spironolactone resulted in improvement in LV end-diastolic filling but no changes in maximal exercise capacity (peak VO₂) on cardiopulmonary exercise testing.

Patients receiving spironolactone also had no improvements in HF symptoms or quality of life, compared with those who received placebo.

The study - the Aldosterone Receptor Blockade in Diastolic HF trial - included 422 patients (mean age, 67 years) with chronic New York Heart Association (NYHA) class II or III HF, LVEF of 50% or greater, echocardiographic evidence of diastolic dysfunction (grade ≥1) or atrial fibrillation, and peak VO₂ of 25 mL/kg per min or less. Patients were randomly assigned to receive either 25 mg spironolactone once daily (n=213) or matching placebo (n=209).

After a mean follow-up of 11.6 months, patients who received spironolactone had significantly improved diastolic function compared with those on placebo. In the spironolactone-treated patients, the ratio of peak early transmitral ventricular filling velocity to early diastolic tissue Doppler velocity (E/e^') declined from 12.7 to 12.1, whereas it increased in the placebo group from 12.8 to 13.6, a significant between-group difference.

However, there were similar increases in peak VO₂ from 16.3 to 16.8 mL/min per kg in the spironolactone group and from 16.4 to 16.9 mL/min per kg in the placebo group.

While the spironolactone patients did have improvements in some other (secondary) echocardiographic endpoints, such as LVEF, LV end-diastolic diameter, LV mass index relative to the placebo group, as well as a slight improvement in 6-minute walk distance, they had no improvements in NYHA class, quality of life, or depressive symptoms.

The authors conclude that the "lack of accepted minimal clinically important differences in E/e^' or peak VO₂ in HF with preserved EF warrants additional prospective, randomized, adequately powered studies to further evaluate the effect of improving diastolic function on symptomatic, functional, and clinical end points."

In a related editorial, John Cleland and Pierpaolo Pellicori (University of Hull, UK) reason that patients in the trial may not have had severe enough cardiac dysfunction to account for impaired exercise capacity, "which could account for the lack of effect of spironolactone."

Noting that ACE inhibitors and angiotensin receptor blockers have been shown to improve clinical endpoints in HF with preserved EF, they conclude that until further data are available, mineralcortiocoid antagonists such as spironolactone "appear useful for managing congestion and preventing diuretic-induced hypokalemia with the attendant risk of sudden arrhythmic death."

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