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Hypertrophic cardiomyopathy (HCM) is a disease of profound phenotypic and genotypic heterogeneity. While HCM-associated mutations are identified usually in patients diagnosed at younger age, the yield of genetic testing and phenotype of patients diagnosed with HCM after 65 years of age (late-diagnosis HCM) is unknown.
Between 1999 and 2007, 1053 unrelated patients with the clinical diagnosis of HCM (60% male, age at diagnosis 44.4±19 years) underwent sarcomeric HCM genetic testing (ACTC1, MYBPC3, MYH7, MYL2, MYL3, TNNC1, TNNI3, TNNT2, TPM1). Comprehensive phenotyping was done by review of electronic medical records and used for genotype-phenotype analyses.
Overall, 160 patients (15%) were diagnosed with HCM after 65 years of age (mean 71.5±5 years) with the majority of patients being female (n=103, 64%). Compared to rest of the HCM cohort (n=893), these patients had less hypertrophy (19.5±5 vs. 21.2±6 mm; p<0.001), and were less likely to have a family history of either HCM (11% vs. 36%; p<0.001) or SCD (10% vs. 22%; p<0.001). Also, they were more likely to have obstructive HCM (56% vs. 46%; p=0.03) and mild concomitant hypertension (66% vs. 31%; p<0.001). Overall, the yield of genetic testing in late-diagnosis HCM was 11% vs. 38% (p<0.001). Patients with late diagnosed HCM and negative genetic test were older at diagnosis (71.7±5 vs. 69.7±3 years; p=0.03) with the majority of such patients having sigmoidal HCM (59%). Only 8% of patients with late diagnosis, sigmoidal HCM had a positive genetic test. Based on our previously established clinical markers for a positive genetic test the yield if genetic test for patients over 65 ranged from 6% when no markers were present to ~30% when all markers were identified.
In this largest genotyped HCM cohort published to date, the overall yield of genetic testing was ~40%. The majority of patients with clinically diagnosed HCM after the age of 65 remains genetically elusive. Most late-diagnosis HCM is likely an acquired/non-genetic subtype of HCM rather than heritable, sarcomeric-HCM with different implications for the screening of first-degree family members.
Moderated Poster Contributions
Poster Sessions, Expo North
Monday, March 11, 2013, 9:45 a.m.-10:30 a.m.
Session Title: What to Look for When Evaluating Hypertrophic Cardiomyopathy
Abstract Category: 23. Pericardial/Myocardial Disease
Presentation Number: 1295M-153
- 2013 American College of Cardiology Foundation