Titin‐truncating variants (TTNtv) have been recognized as the most prevalent genetic cause of dilated cardiomyopathy. However, their effects on phenotypes of left ventricular non‐compaction cardiomyopathy (LVNC) remain largely unknown.
TTN was comprehensively screened by targeted sequencing in a cohort of 83 adult patients with LVNC. Baseline and follow‐up data of all participants were collected. The primary endpoint was a composite of death and heart transplantation. The secondary endpoint was heart failure (HF) events, a composite of HF‐related death, heart transplantation, and HF hospitalization.
Overall, 13 TTNtv were identified in 13 patients, with 9 TTNtv located in the A‐band of titin. There was no significant difference in baseline characteristics between patients with and without TTNtv. During a median follow‐up of 4.4 years, no significant difference in death and heart transplantation between the two groups was observed. However, more HF events occurred in TTNtv carriers than in non‐carriers ( P = 0.006). Multivariable analyses showed that TTNtv were associated with an increased risk of HF events independent of sex, age, and baseline cardiac function (hazard ratio: 3.25, 95% confidence interval: 1.50‐7.01, P = 0.003). Sensitivity analysis excluding non‐A‐band TTNtv yielded similar results, but with less strength.