Echocardiography-guided genetic testing in hypertrophic cardiomyopathy: septal morphological features predict the presence of myofilament mutations

Mayo Clin Proc. 2006 Apr;81(4):459-67. doi: 10.4065/81.4.459.


Objective: To examine the relationship among age, septal morphological subtype, and presence of hypertrophic cardiomyopathy (HCM)-associated myofilament mutations.

Patients and methods: Comprehensive mutation analysis of the 8 HCM susceptibility genes that encode the myofilaments of the cardiac sarcomere was performed previously in 382 unrelated patients with HCM. Blinded to genotype status, we used echocardiography to characterize the left ventricular morphological features. Multivariate regression was used to assess the relationship among morphological subtypes, clinical data, and genetic variables.

Results: The mean +/- SD age of the patients was 41.6+/-19.0 years, with 126 patients 50 years or older at initial diagnosis. The septal morphological subtype was sigmold in 181 (47%), reverse in 132 (35%), apical variant in 37 (10%), and neutral in 32 (8%). The HCM-associated myofilament mutations were Identified in 143 patients (37%). Multivariate analysis showed that the reverse curvature septal morphological subtype was a strong predictor of genotype-positive status (odds ratio, 21; P<.001). Overall, the yield of HCM genetic testing was 79% in the setting of reverse curvature HCM but only 8% in sigmold septal HCM.

Conclusion: In stark contrast to HCM in young patients, elderly patients with HCM display a predominantly sigmoid septal morphological subtype and uncommonly have perturbations of known HCM susceptibility genes. Independent of age, septal morphological subtype strongly predicts the presence or absence of HCM-associated myofilament mutations and may enable echocardiography-guided genetic testing for HCM.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / genetics*
  • Adult
  • Aged
  • Cardiomyopathy, Hypertrophic / diagnosis*
  • Cardiomyopathy, Hypertrophic / genetics
  • DNA Mutational Analysis
  • Echocardiography / methods*
  • Female
  • Follow-Up Studies
  • Genotype
  • Heart Septum / diagnostic imaging*
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Observer Variation
  • Odds Ratio
  • Retrospective Studies