Electrocardiographic features of sarcomere mutation carriers with and without clinically overt hypertrophic cardiomyopathy

Abstract

In hypertrophic cardiomyopathy (HC), electrocardiographic (ECG) changes have been postulated to be an early marker of disease, detectable in sarcomere mutation carriers when left ventricular (LV) wall thickness is still normal. However, the ECG features of mutation carriers have not been fully characterized. Therefore, we systematically analyzed ECGs in a genotyped HC population to characterize ECG findings in mutation carriers (G+) with and without echocardiographic LV hypertrophy (LVH), and to evaluate the accuracy of ECG findings to differentiate at-risk mutation carriers from genetically unaffected relatives during family screening. The ECG and echocardiographic findings were analyzed from 213 genotyped subjects (76 G+/LVH-, 57 G+/LVH+ overt HC, 80 genetically unaffected controls). Cardiac magnetic resonance imaging was available on a subset. Q waves and repolarization abnormalities (QST) were highly specific (98% specificity) markers for LVH- mutation carriers, present in 25% of G+/LVH- subjects, and 3% of controls (p <0.001). QST ECG abnormalities remained independently predictive of carrying a sarcomere mutation after adjusting for age and impaired relaxation, another distinguishing feature of G+/LVH- subjects (odds ratio 8.4, p = 0.007). Myocardial scar or perfusion abnormalities were not detected on cardiac magnetic resonance imaging in G+/LVH- subjects, irrespective of the ECG features. In overt HC, 75% had Q waves and/or repolarization changes, but <25% demonstrated common isolated voltage criteria for LVH. In conclusion, Q waves and repolarization abnormalities are the most discriminating ECG features of sarcomere mutation carriers with and without LVH. However, owing to the limited sensitivity of ECG and echocardiographic screening, genetic testing is required to definitively identify at-risk family members.

Conflict of interest statement

DISCLOSURES

The authors have no conflicts of interest to report.

Copyright © 2011 Elsevier Inc. All rights reserved.

Figures

Figure 1. Distinguishing ECG Abnormalities in G+/LVH− Subjects

Panels A, B, C: Q waves (black arrows), and repolarization changes (T wave inversions (asterisks) and/or ST segment depressions (grey arrows)) were significantly more common in G+/LVH− subjects than G− normal control relatives. IVS = interventricular septum thickness by echo.

Figure 2. The Frequency of Key ECG Abnormalities

Q waves, repolarization abnormalities, or the presence of either (QST) were significantly more prevalent in G+/LVH− subjects than controls. QST was also the most common and distinguishing abnormality in overt HC (G+/LVH+). Notably, commonly used isolated LVH voltage criteria (Sokolow-Lyon, Cornell) were not more common in G+/LVH− subjects and were present in only a minority of patients with overt HC. Normal = absence of major or minor ECG abnormalities; Qw = Q waves; SL = Sokolow-Lyon; Repol. = T wave inversions and/or ST segment depressions; QST = Q waves, T wave inversions and/or ST segment depressions. * p