Author + information
- Mário Santos, MD and
- Adelino F. Leite-Moreira, MD, PhD∗ ()
- ↵∗Department of Physiology and Cardiothoracic Surgery, Cardiovascular R&D Unit Faculty of Medicine, Universidade do Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal
We read with great interest the paper by Kosmala et al. (1) in which they report the increased exercise capacity associated with an improved left ventricular (LV) filling pressure in patients with heart failure with preserved ejection fraction (HFpEF) treated with ivabradine. In addition to the mechanisms elegantly discussed by the authors, we would like to point out other potential important contributors to the observed effect.
Heart rate (HR) is one of the major diastolic function determinants. Indeed, an increase in HR may shorten the diastole duration, precluding myocardial relaxation from being complete, and resulting in increased filling pressures. This may be particularly relevant in the setting of slower relaxation, as may be observed in HFpEF patients. Slow incomplete relaxation can be induced by excessive afterload to such an extent that it leads to marked increases in filling pressures. When the ejection fraction is preserved, the effect of afterload is particularly evident and significantly exacerbated at higher pre-loads (2). Moreover, in contrast to normal hearts, the myocardium of heart failure patients may exhibit a flat or negative myocardial relaxation velocity to HR relationship, even at a lower range of HR (3). Consequently, lowering the HR during early exercise would prevent the clinical expression of this HR-dependent relaxation impairment.
Finally, as Reil et al. (4) recently showed, ivabradine decreases arterial elastance through an enhancement of arterial compliance and a reduction in HR. This reduction in global LV afterload could also contribute to the short-term increase in exercise tolerance described in the ivabradine-treated HFpEF patient group.
The absence of a negative lusitropic pharmacological action and the ability to modulate these diastolic function determinants (HR and afterload) make ivabradine a mechanistically very attractive drug in HFpEF treatment. Future clinical trials will give the critical verdict.
- American College of Cardiology Foundation
- Kosmala W.,
- Holland D.J.,
- Rojek A.,
- Wright L.,
- Przewlocka-Kosmala M.,
- Marwick T.H.
- Zile M.R.,
- Brutsaert D.L.
- Reil J.C.,
- Tardif J.C.,
- Ford I.,
- et al.