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

Study Questions:

Does a mutation in the cardiac troponin T gene (TNNT2) portend a high risk of sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM)?


Adults and children with HCM (n = 522) were screened for the TNNT2 gene mutation. An additional 236 relatives gave consent for clinical and genetic screening for HCM. Probands and relatives underwent both electrocardiograms (ECGs) and echocardiograms. Left ventricular hypertrophy (LVH) from ECG was defined as a score ≥5 using the Romhilt-Estes criteria. Diagnostic criteria for HCM from echocardiogram was defined as a maximum LV wall thickness (MLVWT) ≥13 mm in one or more myocardial segment or a MLVWT exceeding two standard deviations corrected for age, size, or gender. Probands and relatives were followed for the occurrence of events (sudden death, death due to heart failure, occurrence of a cardiac transplant, other cardiovascular death, noncardiovascular death). Event rates were compared to reported historical rates in HCM. Mean follow-up for adults and children was 10 ± 5 and 8 ± 3 years, respectively.


A TNNT2 mutation was found in 3.6% of the 522 HCM patients and 30% of the 236 relatives screened. In the mutation carriers studied, 90% of children (19 of 21) and 24% of adults (16 of 71) had a normal echocardiogram. The ECG was normal in 68% of children, but only 19% of adults. Only 10% of adults with the TNNT2 had both a normal echo and normal ECG. In patients and relatives with a TNNT2 mutation, the rate of sudden cardiac death was 0.93% and the rate of cardiovascular death, transplant, or ICD discharge was 1.6%.


TNNT2 mutations rarely cause LVH in children. About 25% of adults with the TNNT2 mutation lack LVH, but adults tend to manifest ECG changes suggestive of LVH. Rates of cardiovascular death in gene carriers were comparable to referral populations.


The authors have investigated the TNNT2 mutation in HCM patients and their genotype-positive family members to see if this particular mutation is associated with more sudden death and/or less hypertrophy, as previously suggested. They did find an important 25% of adult gene carriers with a normal echocardiogram. Of those who had abnormal echocardiograms, the distribution of LVH was similar to that of other HCM sarcomere mutations. As noted with other gene mutations, phenotype and penetrance in HCM is variable. While the cumulative incidence of sudden death was not higher than that of other HCM sarcomere types, the large number of individuals with a normal echo is concerning. Certainly, more studies or registries are needed to further examine these ‘normal’ patients and to determine if LVH manifests later (adult follow-up only mean of 10 years), and to determine if their risk of sudden death is also higher than that of the general population.

Clinical Topics: Heart Failure and Cardiomyopathies, Heart Failure and Cardiac Biomarkers

Keywords: Mutation, Hypertrophy, Left Ventricular, Biological Markers, Cardiomyopathy, Hypertrophic, Troponin T, Electrocardiography

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