Abstract 4864: Distinct Myocardial Effects of Beta-Blocker Therapy in Heart Failure with Normal and Reduced Left Ventricular Ejection Fraction
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 unequal outcome of β-blocker therapy in trials or registries of HFNEF and HFREF patients with mixed results in HFNEF and positive results in HFREF. To investigate if β-blocker therapy induces disparate effects in HFNEF and HFREF, the present study compares myocardial structure, function and protein composition in HFNEF (n=36) and HFREF (n=43) patients without or with β-blocker therapy (β− HFNEF, β+ HFNEF, β− HFREF, β+ HFREF). All patients were free of coronary artery disease. LV endomyocardial biopsies were used to assess collagen volume fraction (CVF) and cardiomyocyte (CM) diameter (D) by histomorphometry, phosphorylation of Troponin I (p-TnI) by PROQ-diamond phophostaining of 1D gels, and expression of β1-β2 adrenoreceptors (β1-AR,β2-AR), and G proteins (Gs, Gi) by Western immunoblotting. CM were isolated from the biopsies,attached to a force transducer and stretched to 2.2 μm to measure active tension (AT), resting tension (RT) and calcium sensitivity (pCa50). Myocardial effects of β-blocker therapy are either shared by HFNEF and HFREF phenotypes, unique to HFNEF or unique to HFREF (Table⇓). Changes in AT, pCa50, p-TnI are shared and are all beneficial for LV contractility. Changes in CVF, CMD and RT are unique to HFNEF and affect diastolic LV function. Lower Gi is unique to HFREF and improves LV contractility.
Conclusion: β-blocker therapy induces myocardial effects unique to HFNEF or HFREF. This explains the dissimilar outcome of beta-blocker therapy in HFNEF and HFREF phenotype.