Results:

A total of 147 patients were included, comprised of 106 patients with DCM at initial evaluation and 41 patients as asymptomatic carriers. Mean age of 106 patients with DCM at first evaluation was 39 years, 42% were female, and one-half had New York Heart Association class II symptoms or worse. Mean ejection fraction (EF) was 40% and 58% had left ventricular (LV) noncompaction (LVNC) morphology by magnetic resonance imaging (MRI). Atrial arrhythmias were noted in 6%, ventricular arrhythmias in 21%, and conduction disease in 21%. Carriers were younger at first evaluation with a mean age of 27 years and 71% had LVNC by MRI. Over a median follow-up duration of 4.5 years, 24% developed DCM. The strongest predictor of DCM was presence of intraventricular conduction delay and LVNC was not associated with DCM onset.

Overall, mean age at DCM onset among all patients was 37 years. Males were younger than females at age of onset and most patients were diagnosed between 20-60 years and phenotypic expression rate was 99% by age 80 years. Occurrence of DCM before the age of 18 years occurred in 16%. Incidence of LV reverse remodeling was similar to the LMNA cohort but lower than the TTN cohort. Overall incidence of malignant ventricular arrhythmias (MVAs) at 5 years was 1% and all these patients had an EF ≤35%. Incidence of end-stage heart failure (HF) at 5 years was 12%, similar to the TTN cohort. Most mutations were in the head region of the protein (65%) and these were more likely to be affected with LVNC than mutations elsewhere in the protein. The mutation location was not associated with MVA or end-stage HF. Patients with MYH7 variants classified as variant of uncertain significance (VUS) had a similar prevalence of MVA and end-stage HF and more likely to have LV reverse remodeling compared with individuals with pathogenic MYH7 variants.