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Clinical Presentation of Left Ventricular Noncompaction Cardiomyopathy and Bradycardia in Three Families Carrying

Agata Paszkowska1, Dorota Piekutowska-Abramczuk2, Elżbieta Ciara2

  • 1Department of Cardiology, The Children's Memorial Health Institute, 04-730 Warsaw, Poland.

Genes
|March 25, 2022
PubMed

Insights

Genetic variants in the HCN4 gene are linked to left ventricular noncompaction (LVNC) and sinus bradycardia, potentially causing early and severe cardiac symptoms. Further assessment of myocardial fibrosis in both ventricles and atria is crucial for these patients.

Area of Science:

  • Cardiology
  • Genetics
  • Molecular Biology

Background:

  • Left ventricular noncompaction (LVNC) is a heterogeneous cardiomyopathy characterized by distinct myocardial layers and prominent trabeculations.
  • LVNC increases risks for heart failure, arrhythmias, and thromboembolic events.
  • Alterations in the HCN4 gene are linked to familial sinus bradycardia, but its association with LVNC is rarely reported.

Purpose of the Study:

  • To investigate the clinical phenotype of families with LVNC and sinus bradycardia.
  • To identify pathogenic variants in the HCN4 gene associated with these conditions.

Main Methods:

  • Enrolled six patients from four families with isolated LVNC.
  • Utilized echocardiography and cardiovascular magnetic resonance (CMR) for diagnosis.
  • Performed next-generation sequencing (NGS) to evaluate the molecular basis.

Main Results:

  • Six children (median age 11) were followed for a median of 12 years.
  • All patients diagnosed with LVNC; five also by CMR.
  • Five patients presented with sinus bradycardia and ascending aorta dilation; four had rare heterozygous HCN4 variants.

Conclusions:

  • HCN4 variants contribute to a complex LVNC phenotype, including sinus bradycardia and aortic dilation.
  • HCN4 alterations may lead to early symptom onset and severe disease progression.
  • Assessing myocardial fibrosis in both ventricles and atria is vital for LVNC patients with sinus bradycardia.
Abstract

Keywords:
HCN4 molecular variantcardiomyopathychildrenlate gadolinium enhancementleft ventricular noncompactionsinus bradycardia

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