Abstract 15325: Chromogranin B Levels are Increased in Myocardial Tissue in the Dyssynchronous Left Ventricle and Relate to Abnormalities in Regional Myocardial Deformation

Abstract

Introduction: Left bundle branch block (LBBB) induces abnormal activation and deformation of the LV wall. Chromogranin B (CgB) levels are increased in myocardium and plasma of heart failure patients and are linked to cardiomyocyte Ca 2+ handling. Hypothesis: That CgB expression is increased in distinct LV regions during LBBB and may be related to regional deformation abnormalities. Methods: CgB and pro-B-type natriuretic peptide (proBNP) protein levels were measured in biopsies from septum and LV lateral wall in 6 dogs with chronic LBBB (16 weeks), 8 control animals, and in 8 dogs with LBBB that received cardiac resynchronization therapy (CRT) between 8 and 16 weeks after creation of LBBB. Regional myocardial strain was assessed by speckle tracking echocardiography, LV volumes by MRI, and hemodynamics were assessed by invasive pressure measurements (LV dP/dt max and min, tau , LVP max and min, and LV end-diastolic pressure). Results: LBBB animals had increased end-diastolic volumes (55±1 vs.45±4 mL, p=0.038) but normal LV ejection fraction (50±3 vs. 55±4 %, p=0.42) compared to control animals. CgB levels were increased in both septum (p<0.001) and LV lateral wall (p=0.01) in LBBB compared to controls, despite no changes in LV proBNP levels, and with the most prominent increment found in the septum (Figure). In LBBB+CRT animals, CgB levels were 36±18% (septum) and 50±11% (LV later wall) lower compared to LBBB animals, but this difference was not statistically significant. Septal CgB levels correlated with septal early systolic rebound stretch (r=0.76, p=0.017) and lateral wall CgB levels with lateral wall pre-ejection stretch (r=0.76, p=0.018), while no correlations were found with LV dimensions or indices of global hemodynamic function. Conclusion: Myocardial CgB expression was increased in the absence of elevated proBNP levels in LBBB animals with preserved systolic function. Local CgB levels appear to relate to abnormal local early-systolic mechanical loading.