Distinct myocardial effects of beta-blocker therapy in heart failure with normal and reduced left ventricular ejection fraction
Hamdani N et al. – Myocardial effects unique to either heart failure (HF) with normal left ventricular ejection fraction (LVEF) (HFNEF) or HF with reduced LVEF (HFREF) may contribute to the dissimilar outcome of beta-blocker therapy in both HF phenotypes. Methods- Study of whether beta-blockers have distinct myocardial effects in HFNEF and HFREF, myocardial structure, cardiomyocyte function, and myocardial protein composition in HFNEF and HFREF pts with/without beta-blockers free of coronary artery disease
- Pt classification: 16 beta-HFNEF, 16 beta+HFNEF, 17 beta-HFREF, 22 beta+HFREF
- LV endomyocardial biopsies for 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 isolated from biopsies to measure active force (Factive), resting force (Fpassive), and calcium sensitivity (pCa50)
Results- Myocardial effects of beta-blocker therapy either shared by HFNEF and HFREF, unique to HFNEF or unique to HFREF
- Shared: higher Factive, higher pCa50, lower phosphorylation of troponin I and myosin-binding protein C, and lower beta-2 adrenergic receptor expression
- Unique to HFNEF: higher Fpassive, lower CVF, lower MyD, and lower expression of stimulatory G protein
- Unique to HFREF: lower expression of inhibitory G protein
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