Mavacamten and left ventricular dysfunction in hypertrophic cardiomyopathy with left bundle branch block

Mavacamten is a cardiac myosin inhibitor used for patients with obstructive hypertrophic cardiomyopathy (oHCM). The efficacy and safety of this negative inotropic agent in oHCM and concomitant left bundle branch block (LBBB) remains largely unknown. This study aimed to explore the interaction between mavacamten treatment and LBBB on longitudinal changes in left ventricular (LV) systolic function and mechanical dyssynchrony.

This multicenter observational study included 127 patients with oHCM treated with mavacamten. Echocardiographic assessment was performed at 4, 8, 12 and 24 weeks after treatment initiation. LV dyssynchrony was visually assessed by the presence of septal flash (SF) and graded using speckle tracking strain imaging of the mid-septal wall.

Baseline LVEF was not significantly different between the LBBB (60% [58; 65]) and non-LBBB cohort (60% [57; 67]) (P = 0.58). For the LBBB cohort, limited mechanical dyssynchrony was observed at baseline, with no patients expressing a LBBB strain stage ≥3 before mavacamten initiation. After 6 months of treatment, there was a significant decrease in LVEF in the LBBB-HCM patients, with a median ∆LVEF of -11% [-28; -5] and LVEF of 46% [35; 58] (P < 0.001). In addition, there was a significant increase in mechanical dyssynchrony, as reflected by higher LBBB-stages (P = 0.007). In multivariable analysis, atrial fibrillation (AF) (P = 0.005), baseline LVEF (P < 0.001) and LBBB status (P < 0.001) were associated with incident LV systolic dysfunction.

In patients with oHCM receiving mavacamten, the presence of LBBB is associated with an increased risk of developing LV systolic dysfunction. These findings underscore the importance of careful patient selection, monitoring and individualized patient management in this population.