Distinct myocardial effects of beta-blocker therapy in heart failure with normal and reduced left ventricular ejection fraction

Nazha Hamdani, Walter J. Paulus, Loek Van Heerebeek, Attila Borbély, Nicky M. Boontje, Marian J. Zuidwijk, Jean G.F. Bronzwaer, Warner S. Simonides, Hans W.M. Niessen, Ger J.M. Stienen, Jolanda Van Der Velden

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

AimsLeft 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 β-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 β-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 β-blockers.Methods and resultsPatients, free of coronary artery disease, were divided into β-HFNEF (n = 16), β+HFNEF (n = 16), β-HFREF (n = 17), and β+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 β-adrenergic signalling and calcium handling proteins by western immunoblotting. Cardiomyocytes were also isolated from the biopsies to measure active force (Factive), resting force (Fpassive), and calcium sensitivity (pCa50). Myocardial effects of β-blocker therapy were either shared by HFNEF and HFREF, unique to HFNEF or unique to HFREF. Higher Factive, higher pCa50, lower phosphorylation of troponin I and myosin-binding protein C, and lower β2 adrenergic receptor expression were shared. Higher Fpassive, 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.

Original languageEnglish
Pages (from-to)1863-1872
Number of pages10
JournalEuropean heart journal
Volume30
Issue number15
DOIs
Publication statusPublished - Aug 1 2009

Keywords

  • Diastole
  • Heart failure
  • Hypertrophy
  • Myocardium
  • β-blockers

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Distinct myocardial effects of beta-blocker therapy in heart failure with normal and reduced left ventricular ejection fraction'. Together they form a unique fingerprint.

  • Cite this

    Hamdani, N., Paulus, W. J., Van Heerebeek, L., Borbély, A., Boontje, N. M., Zuidwijk, M. J., Bronzwaer, J. G. F., Simonides, W. S., Niessen, H. W. M., Stienen, G. J. M., & Van Der Velden, J. (2009). Distinct myocardial effects of beta-blocker therapy in heart failure with normal and reduced left ventricular ejection fraction. European heart journal, 30(15), 1863-1872. https://doi.org/10.1093/eurheartj/ehp189