Toronto hypertrophic cardiomyopathy genotype score for prediction of a positive genotype in hypertrophic cardiomyopathy

Circ Cardiovasc Genet. 2013 Feb;6(1):19-26. doi: 10.1161/CIRCGENETICS.112.963363. Epub 2012 Dec 13.


Background: Genotyping in hypertrophic cardiomyopathy has gained increasing attention in the past decade. Its major role is for family screening and rarely influences decision-making processes in any individual patient. It is associated with substantial costs, and cost-effectiveness can only be achieved in the presence of high-detection rates for disease-causing sarcomere protein gene mutations. Therefore, our aim was to develop a score based on clinical and echocardiographic variables that allows prediction of the probability of a positive genotype.

Methods and results: Clinical and echocardiographic variables were collected in 471 consecutive patients undergoing genetic testing at a tertiary referral center between July 2005 and November 2010. Logistic regression for a positive genotype was used to construct integer risk weights for each independent predictor variable. These were summed for each patient to create the Toronto hypertrophic cardiomyopathy genotype score. A positive genotype was found in 163 of 471 patients (35%). Independent predictors with associated-risk weights in parentheses were as follows: age at diagnosis 20 to 29 (-1), 30 to 39 (-2), 40 to 49 (-3), 50 to 59 (-4), 60 to 69 (-5), 70 to 79 (-6), ≥80 (-7); female sex (4); arterial hypertension (-4); positive family history for hypertrophic cardiomyopathy (6); morphology category (5); ratio of maximal wall thickness:posterior wall thickness <1.46 (0), 1.47 to 1.70 (1), 1.71 to 1.92 (2), 1.93 to 2.26 (3), ≥2.27 (4). The model had a receiver operator curve of 0.80 and Hosmer-Lemeshow goodness-of-fit P=0.22.

Conclusions: The Toronto genotype score is an accurate tool to predict a positive genotype in a hypertrophic cardiomyopathy cohort at a tertiary referral center.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Cardiomyopathy, Hypertrophic / diagnosis*
  • Cardiomyopathy, Hypertrophic / diagnostic imaging
  • Cardiomyopathy, Hypertrophic / genetics*
  • Cohort Studies
  • Echocardiography
  • Female
  • Genetic Testing / methods*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Models, Genetic
  • Young Adult