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. 2025 Apr 26;16(5):494.
doi: 10.3390/genes16050494.

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

Antheia Kissopoulou  1 , Rada Ellegård  2 , Eva Ingemarsdotter Fernlund  3   4 , Jan-Erik Karlsson  1 , Henrik Green  5   6 , Cecilia Gunnarsson  2   7
Affiliations

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

Antheia Kissopoulou et al. Genes (Basel). .

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 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.

Keywords: apical aneurysm; apical hypertrophy; cardiomyopathy; genetic variant; sarcomere.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
The ECG of a male patient from this cohort with pure apical hypertrophy of 16 mm demonstrates profound negative T-wave inversion in precordial leads and voltage criteria for LV hypertrophy. ECG, electrocardiogram; LV, left ventricular.
Figure 2
Figure 2
CMR demonstrates a thickened LV apex in a female patient of this study with wall thickness extending to the midventricular septum, indicating a “mixed ApHCM” (distal-dominant form). Note the presence of LGE in the hypertrophied apex (red arrow) as well as the apical aneurysm. ApHCM, apical hypertrophic cardiomyopathy; CMR, cardiac magnetic resonance imaging; LGE, late gadolinium enhancement; LV, left ventricular.
See this image and copyright information in PMC

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