Beta-blocker therapy has effects unique to HF with normal or reduced LVEF
7 August 2009
MedWire News: Beta-blocker therapy has unique myocardial effects in heart failure (HF) patients with normal and reduced left ventricular ejection fraction (LVEF), possibly contributing to the different outcomes of therapy for each phenotype, reports a Dutch team.
Walter Paulus (VU University Medical Center, Amsterdam, The Netherlands) and colleagues compared myocardial structure, cardiomyocyte function, and myocardial protein composition in HF patients with normal or reduced LVEF, with or without beta-blocker therapy.
The study included a total of 71 patients, 32 with normal LVEF, of whom 16 were and 16 were not taking beta blockers, and 39 with reduced LVEF, of whom 22 were on beta-blocker therapy and 17 were not.
The researchers assessed collagen volume fraction (CVF), cardiomyocyte diameter (MyD), phosphorylation of myofilamentary proteins, expression of β-adrenergic signaling and calcium handling proteins, and cardiomyocyte function in LV endomyocardial biopsies taken from the patients on suspicion of infiltrative or inflammatory myocardial disease.
They report in the European Heart Journal that shared effects of beta-blocker therapy that are “beneficial for cardiomyocyte contractile performance” were enhanced myocyte calcium sensitivity and active force, reduced phosphorylation of troponin I and myosin-binding protein C, and reduced β2-adrenergic receptor expression.
Effects of beta-blocker therapy unique to patients with normal LVEF were reduced interstitial fibrosis, regression of cardiomyocyte hypertrophy, elevated resting force of cardiomyocytes before and after protein kinase A (PKA) administration and elevated calcium sensitivity after adding PKA, and reduced expression of stimulatory G protein, whereas reduced inhibitory G protein expression was unique to HF with reduced LVEF.
Of note, the lower MyD and higher resting force of cardiomyocytes with beta-blocker treatment in HF with normal LVEF likely relates to the hypertrophied and stiff cardiomyocytes characterisistc of this phenotype, say Paulus and team.
Meanwhile, unchanged CVF in HF patients with reduced LVEF signals poor outcome of beta-blocker therapy for those with intense myocardial fibrosis, they summarize, whereas lower G protein inhibition contributes to improve myocardial contractile performance.
“Unequal outcome of beta-blocker therapy in HF with normal LVEF and HF with reduced LVEF could related to myocardial effects of beta-blocker therapy, which are unique to either HF with normal or HF with reduced LVEF,” the researchers conclude.
