Electrocardiographic Findings in Genotype-Positive and Non-sarcomeric Children with Definite Hypertrophic Cardiomyopathy and Subclinical Variant Carriers

Priyanka Anvekar; Paul Stephens Jr; Renzo J C Calderon-Anyosa; Hunter L Kauffman; Danielle S Burstein; Alyssa L Ritter; Rebecca C Ahrens-Nicklas; Victoria L Vetter; Anirban Banerjee

doi:10.1007/s00246-023-03281-z

Electrocardiographic Findings in Genotype-Positive and Non-sarcomeric Children with Definite Hypertrophic Cardiomyopathy and Subclinical Variant Carriers

Pediatr Cardiol. 2023 Sep 19. doi: 10.1007/s00246-023-03281-z. Online ahead of print.

Authors

Priyanka Anvekar¹, Paul Stephens Jr^{2

3}, Renzo J C Calderon-Anyosa⁴, Hunter L Kauffman², Danielle S Burstein^{2

3}, Alyssa L Ritter⁵, Rebecca C Ahrens-Nicklas^{5

3}, Victoria L Vetter^{2

3}, Anirban Banerjee^{2

3}

Affiliations

¹ Division of Cardiology, Department of Pediatrics, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA. Priyankaanvekar.pa@gmail.com.
² Division of Cardiology, Department of Pediatrics, The Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA, 19104, USA.
³ Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁴ McGill University, Montreal, QC, H3A 0G4, Canada.
⁵ Division of Human Genetics and Metabolism, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, 19104, USA.

PMID: 37725123
DOI: 10.1007/s00246-023-03281-z

Abstract

In children with hypertrophic cardiomyopathy (HCM), the genotype-phenotype association of abnormal electrocardiographic (ECG) features in the backdrop of gene positivity has not been well described. This study aimed to describe the abnormal ECG findings in children with HCM harboring who have genetic variants and determine the association with major adverse cardiac events (MACE). We retrospectively analyzed 81 variants-positive, phenotype-positive (V+P+), 66 variant-positive, phenotype-negative (V+P-), and 85 non-sarcomeric subjects. We analyzed ECG findings and clinical outcomes in the three groups of subjects. Repolarization abnormalities (ST and T wave changes) and pathologic Q waves were the most common abnormalities in variant and non-sarcomeric subjects. The V+P+ group showed higher occurrence of ST segment changes and T wave abnormalities compared to V+P- group. Independent predictors of MACE included ST segment changes (OR 3.54, CI 1.20-10.47, p = 0.022). T wave changes alone did not predict outcome (OR 2.13, CI 0.75-6.07, p = 0.157), but combined repolarization abnormalities (ST+T changes) were strong predictors of MACE (OR 5.84, CI 1.43-23.7, p = 0.014) than ST segment changes alone. Maximal wall z score by echocardiography was a predictor of MACE (OR 1.21, CI 1.07-1.37, p = 0.002). Despite the presence of significant myocardial hypertrophy (z score > 4.7), voltage criteria for LVH were much less predictive. In the non-sarcomeric group, RVH was significantly associated with MACE (OR 3.85, CI 1.08-13.73, p = 0.038). These abnormal ECG findings described on the platform of known genetic status and known myocardial hypertrophy may add incremental value to the diagnosis and surveillance of disease progression in children with HCM. Select ECG findings, particularly repolarization abnormalities, may serve as predictors of MACE in children.

Keywords: Electrocardiogram; Gene variants; Hypertrophic cardiomyopathy (HCM); Non-sarcomeric HCM; Repolarization abnormalities; Sarcomeric HCM; Sudden cardiac death (SCD).