β-Blockers and ivabradine differentially affect cardiopulmonary function and left ventricular filling index

Patients with left ventricular (LV) diastolic dysfunction are characterized by exertional dyspnoea. Heart rate (HR) reduction by β-blockers can improve exercise tolerance by prolonging LV filling, but their negative inotropic and lusitropic properties can be detrimental in this disease. We tested the effects of administering ivabradine, a HR-lowering drug without impact on cardiac kinetics that may favorably affect diastolic function.

Twenty-four patients with coronary artery disease (CAD) and normal LV ejection fraction on chronic β-blocker therapy were included. NT-proBNP serum levels were determined prior to and after cardiopulmonary exercise. β-Blockers were then replaced by ivabradine and patients were re-tested after 6 weeks. Patients were initially classified as having a low (E/e' ≤ 8; n = 11) or high (E/e' > 8; n = 13) LV filling index.

E/e' significantly decreased during ivabradine therapy in patients with high E/e' (10.7 ± 2.9 vs. 8.9 ± 1.7; p < 0.01), whereas no difference occurred in patients with low E/e' (6.4 ± 0.7 vs. 6.5 ± 1.1; p = ns). With ivabradine, patients with high E/e' had an increased oxygen uptake at the anaerobic threshold (from 10.8 ± 1.4 to 11.8 ± 1.9 ml/min/kg; p < 0.05) and a steeper slope of the initial oxygen pulse curve (from 293 ± 109 to 359 ± 117 µl/beat/kg/W; p < 0.05). Moreover, patients with high E/e' had lower NT-proBNP serum levels at rest (169 ± 207 vs. 126 ± 146 pg/ml; p < 0.05) and after exercise (190 ± 256 vs. 136 ± 162 pg/ml; p < 0.05) during ivabradine therapy.

In patients with CAD and elevated E/e', switching therapy from β-blockers to ivabradine may cause a reduction in LV filling pressures and an improved stroke volume response to exercise.