Author + information
- Wojciech Kosmala, MD, PhD and
- Thomas H. Marwick, MBBS, PhD, MPH∗ ()
- ↵∗Baker Heart and Diabetes Institute, 75 Commercial Road, PO Box 6492, Melbourne, Victoria 3004, Australia
We appreciate the interest of Drs. Peverill and Gelman in our trial of spironolactone in patients with heart failure with preserved ejection fraction (HFpEF) (1). In addition to their comments about benefits of excluding atrial fibrillation and ischemia, an important contributor to homogeneity in this study group was the use of the abnormal left ventricular filling pressure response to exercise as a selection criterion.
We agree with Drs. Peverill and Gelman that the mechanism of improved exercise tolerance with spironolactone is unclear. Although we considered the possibility that diuresis caused a reduction in left atrial pressure at rest and during exertion, it would be difficult to understand how this could occur without a reduction of E or E/A ratio, which was not observed (Table 1). Again, the small reduction of blood pressure with spironolactone could contribute to the increase in tissue velocities in the treatment but not the placebo groups (Table 1). However, the correlations of systolic blood pressure with Δe′ lateral at rest (r = 0.21; p = 0.09) and Δe′ septal at rest (r = 0.06; p = 0.59) were not significant. Although the suggestion that demonstration of an early change might support hemodynamic changes as the primary driver, it should be kept in mind that diffuse fibrosis is surprisingly labile, with collagen synthesis at a rate of 5% per day (2), so it will be difficult to exclude an antifibrotic effect. For this purpose, direct imaging of fibrosis might provide interesting data.
Impaired functional capacity is an important target (3), and the findings of our study are concordant with improved exercise capacity in previous studies (4). The antifibrotic properties of spironolactone represent only 1 of the potential mechanisms accounting for the beneficial impact of this medication in HFpEF. Although we, too, would like to understand the mechanism of effect of spironolactone in this study better, we also hope that the effect—irrespective of mechanism—should dispel the therapeutic nihilism that no therapy is effective in the management of HFpEF.
Please note: Both authors have reported that they have no relationships relevant to the contents of this paper to disclose. P.K. Shah, MD, served as Guest Editor-in-Chief for this paper. Bertram Pitt, MD, served as Guest Editor for this paper.
- 2017 American College of Cardiology Foundation
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