CardiomyopathyElectrocardiographic Features of Sarcomere Mutation Carriers With and Without Clinically Overt Hypertrophic Cardiomyopathy
Section snippets
Methods
Genotyped HC probands and relatives identified by research protocols or through clinical evaluation were studied. Research subjects were recruited from 3 institutions: Brigham and Women's Hospital (n = 106), the Minneapolis Heart Institute Foundation (n = 57), and Copenhagen University Hospital (n = 50). Genetic status was previously determined in the family proband by direct DNA sequencing of 8 sarcomere genes, including myosin-binding protein C (MYBPC3), β-myosin heavy chain (MYH7), cardiac
Results
A total of 213 subjects from 60 different families were evaluated, including 76 G+/LVH− subjects, 57 overt (G+/LVH+) HC, and 80 genotype-negative (G−) healthy relatives who served as the normal controls. The clinical and echocardiographic characteristics are summarized in Table 2. Reflecting the age-dependent penetrance of LVH, the overt HC cohort was nearly 2 decades older than the G+/LVH− cohort. Pediatric subjects (<18 years) constituted 42% of the G+/LVH− cohort compared to 33% and 4% of
Discussion
Q waves and repolarization abnormalities are the most distinguishing ECG manifestations of sarcomere mutations in both early (G+/LVH−) and overt (G+/LVH+) HC. Despite the key role that increased LV wall thickness plays in the diagnosis of the disease, isolated ECG voltage criteria for LVH are neither sensitive nor specific markers of HC. Voltage criteria without accompanying repolarization abnormalities are frequently absent in sarcomere mutation carriers, including those with clinically overt
Acknowledgment
We are indebted to Calum A. MacRae, MBCHB, PhD for his careful reading of our manuscript and insightful comments.
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This work was supported by grant K23 HL078901 from the National Institutes of Health, Bethesda, Maryland (to C.Y.H.), Hearst Foundation, New York, New York (to B.J.M.), and the American College of Cardiology/Merck Research Foundation, Washington, DC (to N.K.L.).