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Genetic arrhythmias complicating patients with dilated cardiomyopathy: How it happens

  • Jeffrey A. Towbin
    Correspondence
    Address reprint requests and correspondence: Dr Jeffrey A. Towbin, Heart Institute, Division of Pediatric Cardiology, Le Bonheur Children’s Hospital, 49 N. Dunlap St, FOB, Room 344, Memphis, TN 38103.
    Affiliations
    Heart Institute, Division of Pediatric Cardiology, Le Bonheur Children’s Hospital, University of Tennessee Health Science Center, Memphis, Tennessee
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Published:October 18, 2019DOI:https://doi.org/10.1016/j.hrthm.2019.10.019
      In this edition of Heart Rhythm Journal, Li et al
      • Li Z.
      • Chen P.
      • Li C.
      • et al.
      Genetic arrhythmias complicating patients with dilated cardiomyopathy.
      report on patients with dilated cardiomyopathy (DCM) and arrhythmias (DCM-A) compared to patients with DCM with no arrhythmias (DCM-NA), with the explicit intent to identify the genetic causes of arrhythmias in DCM. Using whole-exome sequencing and high-depth targeted next-generation sequencing followed by Sanger sequencing of all causative variants to eliminate false-positive results, 8 specific DCM-A pedigrees and 2 separate cohorts of 1232 consecutive unrelated sporadic DCM-NA patients were studied (550 patients in discovery cohort; 682 patients in replication cohort). Of these patients, 470 had DCM-A (250 in discovery cohort; 220 in replication cohort) and 762 had DCM-NA (300 in discovery cohort; 462 in replication cohort). Pathogenic variants were identified in genes known to cause long QT syndrome (LQTS) that independently co-segregated in 2 unrelated DCM-LQTS pedigrees. Pathogenic variants in arrhythmia-related genes were identified in 4.9% of sporadic DCM-A patients (4.0% in discovery cohort; 5.9% in replication cohort) but in only 0.1% of sporadic DCM-NA patients. These arrhythmia-related pathogenic variants included those resulting in LQTS, atrial fibrillation (AF), sick sinus syndrome (SSS), cardiac conduction disease (CCD), and Brugada syndrome (BrS). The authors concluded that some arrhythmias in DCM patients are caused by arrhythmia-related pathogenic variants in ion channel-encoding genes.
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