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Updated: Jan 19, 2026
Cardiomyopathy II: Dilated Cardiomyopathy
Published on: June 19, 2025
Genetic arrhythmias complicating patients with dilated cardiomyopathy
Zongzhe Li1, Peng Chen1, Chenze Li2
1Division of Cardiology, Departments of Internal Medicine and Genetic Diagnosis Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China.
Insights
Genetic variants are a significant cause of arrhythmias in dilated cardiomyopathy (DCM) patients. This study found that arrhythmia-related pathogenic variants were common in DCM patients with arrhythmias, suggesting genetic screening can aid diagnosis.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Genomics
Background:
- Malignant arrhythmias leading to sudden cardiac death are common in dilated cardiomyopathy (DCM).
- The genetic basis for arrhythmias in DCM patients remains largely unknown.
Purpose of the Study:
- To investigate the genetic underpinnings of arrhythmias in patients diagnosed with dilated cardiomyopathy.
Main Methods:
- Whole-exome sequencing and targeted next-generation sequencing of 142 genes were performed.
- Analysis included eight DCM pedigrees with arrhythmias and 1232 unrelated DCM patients (470 with arrhythmias, 762 without).
- Sanger sequencing and control screening validated identified variants.
Main Results:
- Pathogenic variants linked to Long QT Syndrome (LQTS) were found in two DCM-LQTS pedigrees.
- Arrhythmia-related pathogenic variants were identified in 4.9% of DCM patients with arrhythmias versus 0.1% without (P < 10^-9).
- These variants included those associated with LQTS, atrial fibrillation, sick sinus syndrome, cardiac conduction disease, and Brugada syndrome.
Conclusions:
- Arrhythmia-related pathogenic variants contribute to arrhythmias in a subset of DCM patients.
- Genetic screening for arrhythmia causes may improve etiological understanding and guide clinical decisions in DCM patients presenting with arrhythmias.
Background:
Sudden cardiac death due to malignant arrhythmias is a common cause of death in dilated cardiomyopathy (DCM). Whether genetic variants increase the risk of arrhythmias in DCM is unknown.
Objective:
The purpose of this study was to investigate the genetic causes of arrhythmias in DCM patients.
Methods:
Whole-exome sequencing and high-depth targeted next-generation sequencing (142-gene panel) were used. Eight specific DCM pedigrees with arrhythmias and 2 separate cohorts of 1232 consecutive unrelated sporadic DCM patients from 3 medical centers (550 in the discovery cohort, 682 in the replication cohort) were analyzed; 470 (250 in the discovery cohort, 220 in the replication cohort) suffered from arrhythmias (DCM-A group) and 762 (300 in the discovery cohort, 462 in the replication cohort) did not (DCM-NA group). All identified causative variants were Sanger sequenced to eliminate false-positive results and then screened in 700 unrelated matched arrhythmia- and DCM-free healthy controls.
Results:
We identified long QT syndrome (LQTS)-causative variants that independently cosegregated in 2 unrelated DCM-LQTS pedigrees. Pathogenic variants in arrhythmia-related genes (ion channelopathies) were identified in 4.9% (23/470) of sporadic DCM-A patients (4.0% in the discovery cohort, 5.9% in the replication cohort) but only 0.1% (1/762) of sporadic DCM-NA patients (P = 2.16 × 10-9). These arrhythmia-related pathogenic variants included long QT syndrome, atrial fibrillation, sick sinus syndrome, cardiac conduction disease, and Brugada syndrome.
Conclusion:
Some arrhythmias in DCM patients are caused by arrhythmia-related pathogenic variants. For DCM patients with explicit arrhythmias, arrhythmia-causative genetic screening may help to explain the etiology and decision-making.
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