Our research recently group proposed an echocardiographic strain-based classification of left bundle branch block (LBBB)-induced cardiomyopathy in heart failure patients (from stage LBBB-1 to LBBB-4). In essence, the higher the LBBB stage, the more the left ventricular (LV) damage is caused by LBBB itself. The staged LBBB classification has potential to risk-stratify and guide clinicians in selecting patients that may most benefit from Cardiac ResynchronizationTherapy (CRT).However, the LBBB classification needs validation and optimization and the paythopysiology of LBBB requires further study. In order to address this, we will:

(1)longitudinally assess the natural history of LBBB patients; we hypothesize that LBBB patients progress towards higher stages in time, thus inferring a pathophysiological continuum of the classification

(2) to assess the reverse remodeling (RR) effects of heart failure medication at the pré-CRT stage, and whether this pharmacological response may be predicted by the staged LBBB classification; we hypothesize that the higher the stage of heart failure patient, the less the (relative) RR effects of heart failure medication and thus advocating early CRT intervention at this stage

(3) following the initial medical treatment phase in (2,) we will test whether the staged LBBB classification will predict the relative extent of RR following CRT

(4) using Circ-Adapt, we will phenotype LBBB-4 patients that have suboptimal CRT response; this will enable to optimize the staged LBBB classificatio

(5) We will study the impact of polygenic risk scores with respect to CRT super-responders vs. non CRT responders and we checck the prevalence of pathogenic DCM mutations along the staged LBBB classification.