Electrocardiography is often advocated as a screening tool in children for hypertrophic cardiomyopathy (HC). We sought to establish an electrocardiographic screening tool to identify children with HC. We hypothesized that a pediatric-specific electrocardiographic criterion would perform better than the popular criteria used for screening children for left ventricular hypertrophy and HC. The earliest available electrocardiogram for children (n = 108) with HC (ages 7 to 21 yrs) was reviewed. We sought to compare the diagnostic accuracy of 4 screening algorithms: (1) Sokolow-Lyon criterion (SV 1 + RV 5 /RV 6 >35 mm), (2) Cornell criterion (RaVL + SV 3 >28 mm in men, 20 mm in women), (3) total 12-lead voltage criterion (R wave to the nadir of Q/S wave >175 mm), and (4) pediatric-specific criterion (RaVL + SV 2 >23 mm). The same criteria were applied to a cohort of age-matched and gender-matched controls without cardiac disease. Statistically significant correlations were found between children with HC and positive screen using all 4 criteria. However, comparison of receiver operating characteristic demonstrated an area under the curve of 0.67 for Sokolow-Lyon criterion, 0.70 for Cornell criterion, 0.83 for total 12-lead criterion, and 0.82 for pediatric-specific criterion. Pediatric-specific criterion had superior sensitivity in gene-positive children and superior overall specificity than total 12-lead criterion. In conclusion, our study demonstrates that the pediatric-specific criterion employing leads RaVL + SV 2 is more accurate in identifying children with HC in comparison with other popular screening criteria.
Hypertrophic cardiomyopathy (HC) is the leading cause of sudden cardiac death in the young (<35 years) in the United States. Great advances have been made in the diagnosis and management of this disease. However, the search and debate for an adequate screening test continues. Multiple studies have demonstrated the inaccuracy of electrocardiography at detection of left ventricular (LV) hypertrophy in children, and there are no reports of sensitivity for screening children for HC in the United States. Our study aims to apply an electrocardiographic screening tool for HC that is tailored for children. We hypothesized that a modified criterion of aVL + SV 2 would be more accurate in detecting HC in children than Sokolow-Lyon, Cornell, or total 12-lead voltage criterion.
Methods
We performed a retrospective cross-sectional study using data that were collected from the HC database compiled at our institution. This includes all patients aged 7 to 21 years managed at a single referral center followed up with the diagnosis of HC (International Classification of Diseases, ninth revision, codes 425.18 and 425.11) from 1991 to 2012. Echocardiography was performed on all patients to determine phenotype. The criteria diagnosis of HC at our center is left ventricular posterior wall thickness at end-diastole >2 standard deviations above the normal mean for body-surface area or localized ventricular hypertrophy: such as, septal thickness >1.5 × left ventricular posterior wall thickness with at least normal left ventricular posterior wall thickness, with or without dynamic outflow obstruction. Genetic testing was offered to all patients with phenotypic findings and patients with family history of HC. A selection of patients, however, did not have genetic testing results for a variety of reasons including failure of insurance to cover testing, family refusal, and pending test results at the time of publication. Patients aged <7 years, diagnosis of other structural heart diseases, and diagnosis of syndromes (Noonan’s syndrome, Friedreich’s ataxia, various metabolic disorders, and so forth) that could account for LV hypertrophy were excluded. Control patients were selected from a database of normal electrocardiograms at Children’s Healthcare of Atlanta. Cases and controls were frequency matched.
The earliest available standard 12-lead electrocardiogram was examined and electrocardiographic parameters were measured by hand with calipers, or electronically when available, by a single observer. As demonstrated in Table 1 , the electrocardiographic voltage criteria were defined as follows on the basis of previous studies: (1) Sokolow-Lyon voltage criterion: SV 1 + RV 5 or RV 6 , whichever is >3.5 mV ; (2) Cornell voltage criterion: RaVL + SV 3 , with 0.8 mV added in women, >2.8 mV ; and (3) total 12-lead voltage, R wave to the nadir of Q/S wave, >175 mm. Our modified pediatric-specific criterion was created based on the observation that V 3 is frequently replaced with V 3 R or V 4 R and, therefore, may vary as a child ages. Additionally, Panza et al described patients with abnormalities of V 1 or V 2 before developing significant ventricular wall thickening, and Montgomery et al reported maximal voltages in leads V 1 and V 2 in patients with HC with phenotypic expression. Therefore, we used a model with RaVL + SV 2 .
| ECG Criterion | Definition |
|---|---|
| Sokolow-Lyon | S wave in V 1 + R wave in V 5 /R wave in V 6 >35 mm |
| Cornell | R wave in aVL + S wave in V 3 >28 mm in men, 20 mm in women |
| Total 12-lead voltage | Sum of total 12-lead voltage (R wave to the nadir of Q/S wave) >175 mm |
| Pediatric-specific | R wave in aVL + S wave in V 2 >23 mm |
A 2-sample t test was used to compare case-control differences. Chi-square analysis was used to determine the accuracy of each screening test in identifying HC. A receiver operating characteristic curve was created for each electrocardiographic screening criterion. Chi-square analysis was used to compare area under the curve (AUC) values. Data were analyzed using the SAS statistical software package (version 9.4; SAS Institute, Cary, North Carolina).
Results
Table 2 lists the clinical demographics, echocardiographic data, and electrocardiographic analysis. Male patients accounted for a slightly higher proportion of our cohort than previous reports. The mean diameter (expressed as a Z score) of the interventricular septum was more hypertrophied than the posterior wall of the LV (3.78 ± 3.31 vs 2.52 ± 2.44). LV outflow tract obstruction was present in 25% of patients with HC. Using the definition in the 2011 American College of Cardiology Foundation/American Heart Association guidelines for HC in children, 78% of patients met the clinical definition of HC of wall thickness ≥2 SDs. Of those who underwent genetic testing, 54% tested positive. The analysis of electrocardiographic recordings demonstrated that the Cornell criterion has the lowest sensitivity, whereas total 12-lead voltage had the highest sensitivity. When analyzing for patients who are phenotype positive, the sensitivities for Sokolow-Lyon, Cornell, total 12-lead voltage, and pediatric-specific criteria were 38%, 46%, 70%, and 73%, respectively. As demonstrated in Figure 1 , pediatric-specific criterion and total 12-lead voltage criterion had very similar AUC of 0.82 and 0.83, respectively. The AUC for pediatric-specific electrocardiographic criterion was statistically significant in comparison with Sokolow-Lyon and Cornell criteria ( Table 3 ).
| Characteristic | Cases (n = 108) | Controls (n = 107) |
|---|---|---|
| Age (yrs) | 12.2 ± 3.6 | 12.3 ± 3.1 |
| Male patients | 77 (71) | 57 (71) |
| Race/ethnicity | ||
| White | 66 (61) | 58 (54) |
| Black | 29 (27) | 40 (37) |
| Latino | 10 (9) | 4 (4) |
| Asian | 1 (1) | 5 (6) |
| Other | 2 (2) | 0 (0) |
| Voltage criteria | ||
| Sokolow-Lyon | 45 (42) | 6 (93) |
| Cornell | 40 (37) | 3 (97) |
| Total 12-lead voltage | 96 (89) | 61 (43) |
| Pediatric-specific | 77 (71) | 8 (93) |
| Echocardiographic | ||
| Interventricular septal thickness in diastole (mm) | 17.2 ± 8.9 | — |
| Interventricular septal thickness in diastole z score | 3.8 ± 3.3 | — |
| LV posterior wall dimension in diastole (mm) | 12.5 ± 5.4 | — |
| LV posterior wall dimension in diastole z score | 2.5 ± 2.4 | — |
| Presence of LV outflow tract obstruction | 27 (25) | — |
| Genotype positive | 37 (54) | — |
