Influence of beta-blockers on mechanical dyssynchrony and cardiac remodeling in patients with ischemic chronic heart failure in the setting of revascularization

Abstract

Introduction: Diastolic dysfunction (DD) and cardiac dyssynchrony (DS) are involved in the progression of chronic heart failure (CHF). A comparative analysis was conducted of the effect of a 6-month course of nebivolol and bisopr­olol on DD, DS and metalloproteinase-9 (MMP-9) level in patients with ischemic chronic heart failure with preserved ejection fraction (HFpEF) and with midrange ejection fraction (HFmrEF), as well as in patients with comorbid type 2 diabetes mellitus (T2DM) in the setting of coronary artery bypass grafting (CABG) after 6 months of therapy.

Materials and methods: The study included 308 patients with CHF FC I-II, left ventricular ejection fraction (LVEF) >40%, who had undergone CABG. The average dose of nebivolol in patients with DS 6 months later was 5.1±2.6 mg/day, and bisoprolol – 4.9±2.4 mg/day. Echocardiography (EchoCG) and evaluation of MMP-9 in blood plasma were performed. Mechanical myocardial asynchrony was determined by calculating the standard deviation of time to peak systolic myocardial velocity (TS-SD) and maximum segment delay (TS12) using a 6-basal and-midsegment model.

Results and discussion: MMP-9 level in patients with CHF before CABG was 4.7 times higher (p<0.001). MMP-9 correlated with LVEF (r=-0.60, p<0.001), E/A (r=-0.49, p<0.001), DT (r=0.43, p<0.001), E` (r=-0.58, p<0.001) and DS: TS12 (r=0.54, p<0.001), TS-SD (r=0.49, p<0.001). The six-month course of nebivolol improved the values of DS: TS12 – by 30% (p<0.001), TS-SD – by 32% (p<0.01) and reduced the MMP-9 level by 11% (p<0.001). In patients with HFmrEF without DS nebivolol increased E/A by 19% (p<0.01), E` – by 16% (P<0.05), and decreased E/E’ by 9% (p<0.05), DT – by 12% (p<0.05). In patients with HFpEF and DM2, nebivolol reduced TS12 by 37% (p<0.01), TS-SD – by 29% (p<0.05) and MMP-9 – by 13% (p<0.05).

Conclusion: The positive effect of nebivolol on the DS, DD of the LV in patients with HFpEF, HFmrEF and with comorbid type 2 diabetes mellitus. The six-month course of nebivolol decreased the MMP-9 level in patients with ischemic CHF after CABG, including patients with T2DM.