Long-Term Outcomes in Hypertrophic Cardiomyopathy Caused by Mutations in the Cardiac Troponin T Gene

Background-Hypertrophic cardiomyopathy caused by mutations in the cardiac troponin T gene (TNNT2) has been associated with a high risk of sudden cardiac death (SCD) and mild left ventricular hypertrophy. However, previous studies are limited by sample size, cross-sectional design, and few data in relatives. Methods and Results-Five hundred fifty-two unrelated hypertrophic cardiomyopathy probands were screened for TNNT2 mutations. First-degree relatives were invited for clinical and genetic evaluation. Ninety-two individuals (20 probands and 72 relatives) carried TNNT2 mutations (51 [55%] male; 30 +/- 17 years). ECGs and echo were available in 87 (95%) and 88 (96%) individuals, respectively. ECG was normal in 13 (68%) children (<16 years) and 13 (19%) adults. Echo was normal in 18 (90%) children and 16 (24%) adults; 7 (10%) adults had a normal ECG and echo. Thirteen (65%) of 20 families had a history of SCD. Follow-up was available for 75 patients (mean, 9.9 +/- 5.2 years); 2 of 16 adults and 2 of 18 children with normal echoes developed left ventricular hypertrophy. Twenty-three (22%) received an implantable cardioverter-defibrillator (20 for primary prophylaxis). One child and 3 adults died of SCD and 2 adults were resuscitated from ventricular fibrillation. One patient had an appropriate implantable cardioverter-defibrillator discharge. The rate of cardiovascular death, transplant, and implantable cardioverter-defibrillator discharge was 1.6% (0.016 person/y; 95% confidence interval, 0.83-2.79%), and SCD 0.93% (0.0093 person/y; 95% confidence interval, 0.37-1.92%). Conclusions-Left ventricular hypertrophy is rare in children with TNNT2 mutations. Left ventricular hypertrophy is absent in the minority of adults, but most have an abnormal ECG. Despite adverse family histories, the rate of cardiovascular death during follow-up was similar to that reported in large referral populations. (Circ Cardiovasc Genet. 2012;5:10-17.)