Dissociation between heart rate reduction and left ventricular filling pressure in heart failure with preserved ejection fraction: a meta-analysis of ivabradine trials

Abstract

Background: Heart rate (HR) reduction is commonly proposed to improve diastolic fi lling and reduce left ventricular (LV) fi lling pressure in heart failure with preserved ejection fraction (HFpEF). Ivabradine selectively lowers HR without direct myocardial effects, providing a mechanistic model to examine whether HR reduction alone translates into improved LV fi lling pressure. This study aims to evaluate whether selective HR reduction with ivabradine improves LV fi lling pressure and diastolic function in patients with HFpEF. Methods: MEDLINE and CENTRAL were systematically searched for randomized controlled trials comparing ivabradine with placebo or standard therapy in HFpEF. Outcomes included diastolic echocardiographic parameters (E/e′, e′ velocity, and left atrial volume index [LAVI]), resting HR, natriuretic peptides, and peak oxygen consumption (peak VO2). Pooled mean differences (MDs) with 95% confi dence intervals (CIs) were calculated using random-effects models. Results: Three RCTs (258 patients) were included. Ivabradine signifi cantly reduced resting HR (MD −12.03 bpm; 95% CI −18.43 to −5.63), yet was associated with a signifi cant increase in E/e′ (MD 1.02; 95% CI 0.22 to 1.82). Septal e′ modestly increased, while no signifi cant differences were observed for lateral or mean e′, LAVI, natriuretic peptides, or peak VO2. Conclusions: These fi ndings suggest a dissociation between HR reduction and LV fi lling pressure, underscoring the limited role of isolated chronotropic modulation in the pathophysiology of HFpE