Beta-blocker therapy was associated with shared myocardial effects in HFNEF and HFREF, and unique effects like lower collagen volume fraction in HFNEF and lower inhibitory G protein in HFREF.
Observational (n=71)
Does beta-blocker therapy have distinct myocardial effects in patients with heart failure with normal versus reduced ejection fraction?
Beta-blocker therapy has distinct myocardial effects in HFNEF compared to HFREF, which may explain the differing clinical outcomes of beta-blockers in these two heart failure phenotypes.
AIMS: Left ventricular (LV) myocardial structure and function differ in heart failure (HF) with normal (N) and reduced (R) LV ejection fraction (EF). This difference could underlie an unequal outcome of trials with beta-blockers in heart failure with normal LVEF (HFNEF) and heart failure with reduced LVEF (HFREF) with mixed results observed in HFNEF and positive results in HFREF. To investigate whether beta-blockers have distinct myocardial effects in HFNEF and HFREF, myocardial structure, cardiomyocyte function, and myocardial protein composition were compared in HFNEF and HFREF patients without or with beta-blockers. METHODS AND RESULTS: Patients, free of coronary artery disease, were divided into beta-(HFNEF) (n = 16), beta+(HFNEF) (n = 16), beta-(HFREF) (n = 17), and beta+(HFREF) (n = 22) groups. Using LV endomyocardial biopsies, we assessed collagen volume fraction (CVF) and cardiomyocyte diameter (MyD) by histomorphometry, phosphorylation of myofilamentary proteins by ProQ-Diamond phosphostained 1D-gels, and expression of beta-adrenergic signalling and calcium handling proteins by western immunoblotting. Cardiomyocytes were also isolated from the biopsies to measure active force (F(active)), resting force (F(passive)), and calcium sensitivity (pCa(50)). Myocardial effects of beta-blocker therapy were either shared by HFNEF and HFREF, unique to HFNEF or unique to HFREF. Higher F(active), higher pCa(50), lower phosphorylation of troponin I and myosin-binding protein C, and lower beta(2) adrenergic receptor expression were shared. Higher F(passive), lower CVF, lower MyD, and lower expression of stimulatory G protein were unique to HFNEF and lower expression of inhibitory G protein was unique to HFREF. CONCLUSION: Myocardial effects unique to either HFNEF or HFREF could contribute to the dissimilar outcome of beta-blocker therapy in both HF phenotypes.
Hamdani et al. (2009) conducted an observational in Heart failure with normal and reduced left ventricular ejection fraction (n=71). Beta-blocker therapy vs. No beta-blocker therapy was evaluated on Myocardial structure, cardiomyocyte function, and myocardial protein composition. Beta-blocker therapy was associated with shared myocardial effects in HFNEF and HFREF, and unique effects like lower collagen volume fraction in HFNEF and lower inhibitory G protein in HFREF.