Abstract 4329: Myocardial Protein Kinase G Activity Differs in Heart Failure with Normal and Reduced Ejection Fraction

Abstract

Concentric left ventricular (LV) remodeling and cardiomyocyte (CM) hypertrophy characterize heart failure with normal ejection fraction (HFNEF) whereas eccentric LV remodeling and low myofilamentary density characterize heart failure with reduced ejection fraction (HFREF). In rodents, low myocardial protein kinase G (PKG) activity has been implicated in the development of pathological CM hypertrophy induced by LV pressure-overload. The present study therefore compared LV remodeling, CM hypertrophy and myocardial PKG activity in patients (pts) with HFNEF (n=36) and HFREF (n=43). All pts had been admitted to hospital for worsening heart failure (NYHA 3–4) and were free of coronary artery disease. HFNEF pts had a LVEF > 50% and a LV end-diastolic pressure > 16 mmHg. HFREF pts had a LVEF <45%. LV remodeling was measured by LV mass/volume ratio derived from biplane LV angiograms and 2D-echocardiograms. CM hypertrophy and myocardial PKG activity were assessed in LV endomyocardial biopsies by histomorphometry of CM diameter and by immunohistochemistry using antibodies against the specific PKG substrate vasodilator stimulated phosphoprotein (VASP) and against phosphorylated VASP ((P)-VASP). Myocardial PKG activity corresponded to the ratio of (P)-VASP/VASP. LV mass/volume ratio and CM diameter were significantly larger in HFNEF than in HFREF (Table ). As evident from (P)-VASP/VASP ratio, PKG activity was lower in HFNEF than in HFREF (Table ). Conclusion: HFNEF patients have lower myocardial PKG activity than HFREF patients. This low myocardial PKG activity could contribute to CM hypertrophy and concentric LV remodeling observed in HFNEF. Raising myocardial PKG activity by phosphodiesterase 5A inhibition could be useful to limit CM hypertrophy and concentric LV remodeling in HFNEF.