Prevalence and Prognostic Impact of Pathogenic Variants in Patients With Dilated Cardiomyopathy Referred for Ventricular Tachycardia Ablation

Micaela Ebert, Adrianus P. Wijnmaalen, Marta de Riva, Serge A. Trines, Alexander F. A. Androulakis, Claire A. Glashan, Martin J. Schalij, J. Peter van Tintelen, Jan D. H. Jongbloed, Katja Zeppenfeld*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

OBJECTIVES This study aimed to assess the frequency of (likely) pathogenic variants (LP/Pv) among dilated cardiomyopathy (DCM) ventricular tachycardia (VT) patients referred for CA and their impact on procedural outcome and long-term prognosis.

BACKGROUND The prevalence of genetic variants associated with monomorphic VT among DCM is unknown.

METHODS Ninety-eight consecutive patients (age 56 +/- 15 years; 84% men, left ventricular ejection fraction [LVEF] 39 12%) referred for DCM-VT ablation were included. Patients underwent electroanatomical mapping and testing of >= 55 cardiomyopathy-related genes. Mapping data were analyzed for low-voltage areas and abnormal potentials. LP/Pv-positive (LP/Pv+) patients were compared with LP/Pv-negative (LP/Pv-) patients and followed for VT recurrence and mortality.

RESULTS In 37 (38%) patients, LP/Pv were identified, most frequently LMNA (n = 11 of 37, [30%]), 17N (n = 6 of 37, [16%]), PLN (n = 6 of 37, [16%]), SCN5A (n = 3 of 37, [8%]), RBM20 (n = 2 of 37, [5%]) and DSP (n = 2 of 37, [5%]). LP/Pv+ carriers had tower LVEF (35 + 13% vs. LP/Pv-: 42 11%; p 0.005) and were less often men (n 27 [73%] vs. n 55 [90%] p 0.03). After a median follow-up of 2.4 years (interquartile range: 0.9 to 4.4 years), 63 (64%) patients had VT recurrence (LP/Pv+: 30 of 37 [81%] vs. LP/Pv-: 33 of 61 [54%]; p = 0.007). Twenty-eight patients (29%) died (LP/Pv +: 19 of 37 [51%] vs. LP/Pv-: 9 of 61 [15%]; p <0.001). The cumulative 2-year VT-free survival was 41% in the total cohort (LP/Pv+: 16% vs. LP/Pv-: 54%; p 0.001). The presence of LP/Pv (hazard ratio: 1.9; 95% confidence interval: 1.1 to 3.4; p = 0.02) and unipolar low-voltage area size/cm(2) increase (hazard ratio: 2.5; 95% confidence interval: 1.6 to 4.0; p <0.001) were associated with a decreased 2-year VT-free survival.

CONCLUSIONS In patients with DCM-VT, a genetic cause is frequently identified. LP/Pv+ patients have a tower LVEF and more extensive VT substrates, which, in combination with disease progression, may contribute to the poor prognosis. Genetic testing in patients with DCM-VT should therefore be recommended. (C) 2020 by the American College of Cardiology Foundation.

Original languageEnglish
Pages (from-to)1103-1114
Number of pages12
JournalJACC. Clinical electrophysiology
Volume6
Issue number9
DOIs
Publication statusPublished - Sept-2020

Keywords

  • catheter ablation
  • dilated cardiomyopathy
  • genetic mutation
  • genetic testing
  • genetic variant
  • inherited cardiomyopathy
  • nonischemic cardiomyopathy
  • ventricular tachycardia
  • NONISCHEMIC CARDIOMYOPATHY
  • CATHETER ABLATION
  • POSITION STATEMENT
  • WORKING GROUP
  • SCAR
  • SUBSTRATE
  • ARRHYTHMIAS
  • PREVENTION
  • MUTATIONS
  • FIBROSIS

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