Myocardial Structural, Perfusion and Metabolic Correlates of Left Bundle Branch Block Mechanical Derangement in Patients with Dilated Cardiomyopathy: A Tagged Cardiac Magnetic Resonance and Positron Emission Tomography Study Running Title: Insights in LBBB Mechanisms by Multi-Imaging

Background – Left bundle branch block (LBBB) influences upon regional left ventricular (LV) structure, perfusion and metabolism were not thoroughly investigated in dilated cardiomyopathy (DCM) patients. Methods and Results – Eleven DCM patients with LBBB (69±11 years, LV ejection fraction[EF]: 35±8%) and 7 DMC patients without LBBB (58±9 years, LV EF: 37±10%) were studied by cardiac magnetic resonance (CMR) and positron emission tomography (PET). Left ventricle was divided in 3 regions: septum, adjacent (anterior-inferior) and lateral. Regional midwall circumferential strain, maximum shortening ( peak) and strain rate were obtained from tagged CMR. Systolic stretch index (SSI) was calculated as positive strain rate (stretching) divided by total strain rate. Myocardial metabolic rate of glucose (MMRG), resting and hyperemic myocardial blood flow (MBF) were quantitated using 2[F]fluoro-2-deoxyglucose and [N]ammonia PET, respectively. Conversely from non LBBB patients, LBBB patients showed highly inhomogeneous systolic deformation pattern which changed gradually moving from discoordinate [(SSI: 0.485 (0.284)] and poorly contracting ( peak: -1.14±0.96%) septum to coordinate [SSI: 0.002 (0.168)] and strongly contracting ( peak: -13.63±2.58%) lateral region (both P<0.0001). This pattern was closely matched to MMRG distribution disclosing lowest, intermediate and highest values respectively in the septum, adjacent and lateral regions (P<0.0001). Septal-to-lateral thickness ratio was lower in LBBB than non LBBB patients (P=0.03). In both groups, LV distribution of resting and hyperemic MBF and MBF reserve did not differ significantly. Conclusions In DCM patients, the extensive LV contraction abnormalities induced by LBBB caused regional myocardial metabolic and structural remodeling without consistent changes in blood flows.