ECG risk score: A powerful predictor of sudden death in hypertrophic cardiomyopathy - genotype correlates

Abstract

Background: An ECG risk score, scoring amplitudes and morphological abnormalities, which predicts a very high relative risk of sudden death if the point score is >5 has been described. The genotype-phenotype relationships, and correlation with sudden death have been studied in a geographical cohort of patients diagnosed with HCM < 19 yrs of age in the West Götaland Region, Sweden. Methods: Diagnosis was established with echocardiography, and ECG risk score was quantified from a 12-lead ECG according to Eur.Heart J 2010;31:439. DNA was analysed at international commercial laboratories. Results: 67 patients had ECG and echocardiographic data, 64% male. 45 (67%) had familial disease, and 12 Noonan-spectrum dysmorphology. Based on ECG-risk score 28 patients were high-risk (>5 points), and 39 low-risk (<6 points). The risk score correlated with death (correlation coefficient 0.57, p < 0.0001); there were 7 sudden deaths in the high-risk group and none in the low risk group (p = 0.0005). Familial disease was more common in the low-risk (85%) than in the high-risk group (37%), but a higher proportion of genotyped individuals had positive findings in the high-risk (81%) than in the low-risk group (67%). MYH7 mutations were more common than MYBPC3 (29% versus 19%) in the high-risk group, whereas in the low-risk group MYBPC was predominant (33%). Additional genes affected in the high-risk group were ACTC, MYL, MYPN, LAMP2, RAF 1 and PTNP11. Conclusions: The simple inexpensive ECG risk score effectively pinpoints high-risk individuals who require urgent full risk assessment, and where the yield of genetic testing is particularly high.