Abstract Introduction and objectives Left bundle branch block cardiomyopathy (LBBB-CM) is an increasingly recognized entity, where electromechanical dyssynchrony seems to play a central role in left ventricular dysfunction (LVD) development. This is a challenging and scarcely studied topic, as causality dilemma between LBBB and LVD is still unsolved. Our aim is to increase current evidence on the subject by analyzing a population of idiopathic LBBB patients (pts) who developed, at some point, LVD not explained by other causes. Methods Retrospective study of LBBB adult pts screened from a large tertiary care hospital electrocardiographic database from 2011 to 2017. After careful evaluation, only possible LBBB-CM pts with serial follow-up (FU) echocardiographic and clinical data were included in the analysis. Results 53 pts were identified as possible LBBB-CMP. At baseline, 44% presented left ventricular ejection fraction (LVEF)>50%, while 56% had LVD. 51% were female and mean age at first-ever LBBB report was 59 years-old. All cohort presented echocardiographic mechanical desynchrony, and additional testing to exclude other causes of LVD (non-invasive ischemia testing in 78%; coronariography in 68%; cardiac magnetic resonance in 38%). Median FU time was 10 years. Worst-LVD was reported as severe in 49% of pts, moderate in 23% and mild in 28%. Median time-to-dysfunction in those with initial LVEF>50% was 8 years. 77% of pts presented heart-failure (HF) symptoms. 40% and 42% presented at least 1 CV event and CV hospitalization, respectively. Most events and/or hospitalizations were due to acute decompensated HF. 2 CV deaths were observed. Cardiac resynchronization therapy (CRT) devices were implanted in 47% of pts. All presented clinical improvement after implantation, and LVEF significantly increased (pre-CRT median LVEF of 24% vs 48% post-CRT; p<0.001). When comparing pts with vs without CRT (Figure 1), better LVEF improvements were achieved in CRT group (median LVEF improvement of 27% in CRT vs 11%; p<0.001). Repeating the latter analysis in pts who only presented at least moderate dysfunction, higher LVEF increase was also reported in CRT group (median LVEF improvement of 27% in CRT pts vs 14%; p=0.002), and significantly more CRT pts recovered LV function (50% CRT vs 14% non-CRT; p=0.028). Notably, no differences were found in rates of medical HF therapy between groups (p=1). Conclusion Our data shows LBBB-CM as a diagnosis of exclusion, where careful evaluation of other LVD etiologies should be performed and discarded. We highlight important morbidity rates in this population, namely HF hospitalizations, as well as the apparently critical role of CRT implantation in these pts. All our CRT pts responded excellently to the therapy. Thus, our study raises awareness to the emerging question of whether this entity can be reversed after LBBB correction with CRT and if early intervention would be desirable.Figure 1