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Unravelling the Genotype of the Apical Variant of Hypertrophic Cardiomyopathy in a Swedish Cohort

Kissopoulou, Antheia ; Ellegård, Rada ; Fernlund, Eva Ingemarsdotter LU orcid ; Karlsson, Jan Erik ; Green, Henrik and Gunnarsson, Cecilia (2025) In Genes 16(5).
Abstract

Background: Apical hypertrophic cardiomyopathy (ApHCM) is a distinct variant of hypertrophic cardiomyopathy (HCM). Few studies have focused on the genetic determinants of this subtype. We aimed to investigate the genetic basis of apical hypertrophy in a Swedish cohort. Methods–Results: Longitudinal data on 58 unrelated index patients with ApHCM from the Southeast healthcare region in Sweden from 2010 to 2024 were assessed retrospectively. Additionally, the original raw data from genetic testing were re-evaluated using AI-based Emedgene software. Patients were 47 ± 14 years old, and 60% males. A total of 72.4% had the pure apical type and the remaining had the mixed phenotype, dominant distal. In the cohort, 50/58 (86.2%) underwent... (More)

Background: Apical hypertrophic cardiomyopathy (ApHCM) is a distinct variant of hypertrophic cardiomyopathy (HCM). Few studies have focused on the genetic determinants of this subtype. We aimed to investigate the genetic basis of apical hypertrophy in a Swedish cohort. Methods–Results: Longitudinal data on 58 unrelated index patients with ApHCM from the Southeast healthcare region in Sweden from 2010 to 2024 were assessed retrospectively. Additionally, the original raw data from genetic testing were re-evaluated using AI-based Emedgene software. Patients were 47 ± 14 years old, and 60% males. A total of 72.4% had the pure apical type and the remaining had the mixed phenotype, dominant distal. In the cohort, 50/58 (86.2%) underwent genetic testing, of whom 7/50 (14%) were considered genotype positive for a pathogenic/likely pathogenic variant, mainly in MYH7 (43%) and in the non-sarcomeric ALPK3 gene (28.6%). A re-evaluation of the original data from genetic testing identified a previously unreported variant in the skeletal muscle α-actin (ACTA1) gene. Overall, 21 of 58 patients (36.2%) had HCM-related events during their disease course: 10% had a stroke, and 12% had heart failure. Atrial fibrillation was present in 41.4% and non-sustained ventricular tachycardia occurred in 29.3% of the patients. Apical aneurysm was observed in 17.2% of cases. Patients with a positive genotype were more likely to have a positive family history of HCM compared to those with a negative genotype (p = 0.020). Conclusions: In ApHCM, a positive genotype was found less frequently compared to classic HCM. Only 14% of patients with ApHCM were found to be genotype positive, indicating that apical hypertrophy represents a genetically unique population with low risk of mortality. Nevertheless, patients with ApHCM faced higher rates of atrial fibrillation, ventricular arrhythmias, and apical aneurysms.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
apical aneurysm, apical hypertrophy, cardiomyopathy, genetic variant, sarcomere
in
Genes
volume
16
issue
5
article number
494
publisher
MDPI AG
external identifiers
  • pmid:40428316
  • scopus:105006758958
ISSN
2073-4425
DOI
10.3390/genes16050494
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 by the authors.
id
c6108e38-5027-4e9a-b542-ee1d3dad80e3
date added to LUP
2025-08-06 12:21:14
date last changed
2025-08-07 03:00:08
@article{c6108e38-5027-4e9a-b542-ee1d3dad80e3,
  abstract     = {{<p>Background: Apical hypertrophic cardiomyopathy (ApHCM) is a distinct variant of hypertrophic cardiomyopathy (HCM). Few studies have focused on the genetic determinants of this subtype. We aimed to investigate the genetic basis of apical hypertrophy in a Swedish cohort. Methods–Results: Longitudinal data on 58 unrelated index patients with ApHCM from the Southeast healthcare region in Sweden from 2010 to 2024 were assessed retrospectively. Additionally, the original raw data from genetic testing were re-evaluated using AI-based Emedgene software. Patients were 47 ± 14 years old, and 60% males. A total of 72.4% had the pure apical type and the remaining had the mixed phenotype, dominant distal. In the cohort, 50/58 (86.2%) underwent genetic testing, of whom 7/50 (14%) were considered genotype positive for a pathogenic/likely pathogenic variant, mainly in MYH7 (43%) and in the non-sarcomeric ALPK3 gene (28.6%). A re-evaluation of the original data from genetic testing identified a previously unreported variant in the skeletal muscle α-actin (ACTA1) gene. Overall, 21 of 58 patients (36.2%) had HCM-related events during their disease course: 10% had a stroke, and 12% had heart failure. Atrial fibrillation was present in 41.4% and non-sustained ventricular tachycardia occurred in 29.3% of the patients. Apical aneurysm was observed in 17.2% of cases. Patients with a positive genotype were more likely to have a positive family history of HCM compared to those with a negative genotype (p = 0.020). Conclusions: In ApHCM, a positive genotype was found less frequently compared to classic HCM. Only 14% of patients with ApHCM were found to be genotype positive, indicating that apical hypertrophy represents a genetically unique population with low risk of mortality. Nevertheless, patients with ApHCM faced higher rates of atrial fibrillation, ventricular arrhythmias, and apical aneurysms.</p>}},
  author       = {{Kissopoulou, Antheia and Ellegård, Rada and Fernlund, Eva Ingemarsdotter and Karlsson, Jan Erik and Green, Henrik and Gunnarsson, Cecilia}},
  issn         = {{2073-4425}},
  keywords     = {{apical aneurysm; apical hypertrophy; cardiomyopathy; genetic variant; sarcomere}},
  language     = {{eng}},
  number       = {{5}},
  publisher    = {{MDPI AG}},
  series       = {{Genes}},
  title        = {{Unravelling the Genotype of the Apical Variant of Hypertrophic Cardiomyopathy in a Swedish Cohort}},
  url          = {{http://dx.doi.org/10.3390/genes16050494}},
  doi          = {{10.3390/genes16050494}},
  volume       = {{16}},
  year         = {{2025}},
}