Idiopathic or iatrogenic left bundle branch block (LBBB) is a unique model of electro-mechanical ventricular dyssynchrony with concordant changes in electrical activation sequence and mechanical ventricle synchronization. In chronic animal models, isolated LBBB induces structural remodeling with progressive left ventricular (LV) dysfunction. Most abnormalities can be reverted after cardiac resynchronization therapy (CRT). In humans, 2 principal models of LBBB dyssynchronopathy can be observed: the chronic model of isolated LBBB and an acute iatrogenic model of new-onset LBBB after aortic valve interventions. Although epidemiological evidence and clinical data need to be strengthened, there is a strong presumption that they may lead to LBBB-induced cardiomyopathy and benefit from CRT to prevent progression to heart failure. A large cohort study with prospective follow-up would be required to better define actual incidence, evolution over time, and predisposing factors. Parallel randomized CRT clinical trials should be conducted in selected at-risk populations: namely, patients with persistent LBBB after transcatheter aortic valve replacement.