Abstract 13373: Specific Genotype Predicts Phenotype and Survival in Familial Transthyretin Cardiomyopathy
More than 100 transthyretin (TTR) mutations are identified which cause familial systemic amyloidosis. Frequency of specific variants differs by geographic location and ethnicity. Reports of cardiac involvement and outcome have been limited by small case numbers due to low prevalence.
Hypothesis: TTR variants differ by cardiac phenotype and survival.
Methods: 386 subjects who underwent genotyping for TTR variants and echocardiography were identified by retrospective review of medical records at our institution. Of these, 197 had TTR variants previously associated with familial systemic amyloidosis and were subgrouped by genotype for comparison.
Results: The 3 largest genotype subgroups included T60A (n=66), V30M (n=42) and V122I (n=21). Remaining subjects (n=68) were distributed amongst 35 different genotypes and excluded from analysis. At mean follow up 3.0±2.8 years there were 63 deaths. Subjects with V122I genotype were older at presentation (p=0.04), and more often had edema (p<0.001) and dyspnea (p<0.001). Septal (p=0.003) and posterior wall thickness (p=0.001), left ventricular (LV) mass index (p=0.003), and right ventricular (RV) systolic pressure (p=0.01) were greater in V122I group and LVEF lower (p<0.001). By echocardiography, V30M TTR variant subjects had least severe cardiac disease and best survival, while V122I had most severe disease and worst survival (Figure; p=0.005).The association of genotype with mortality persisted after adjustment for age, sex, septal and posterior wall thickness, and LVEF. This association was attenuated by RV systolic pressure and LV mass index.
Conclusion: For familial TTR amyloid cardiomyopathy, specific genotype predicts both severity of phenotypic expression as measured by echocardiography and survival. These results suggest routine clinical genotyping of TTR variants may improve risk prediction, and tailor treatment by identification of patients at highest risk of adverse outcomes.
- © 2011 by American Heart Association, Inc.