Author + information
- Received January 3, 2020
- Revision received April 13, 2020
- Accepted April 20, 2020
- Published online July 29, 2020.
- Micaela Ebert, MDa,
- Adrianus P. Wijnmaalen, MD, PhDa,
- Marta de Riva, MDa,
- Serge A. Trines, MD, PhDa,
- Alexander F.A. Androulakis, MDa,
- Claire Glashan, MDa,
- Martin J. Schalij, MD, PhDa,
- J. Peter van Tintelen, MD, PhDb,c,
- Jan D.H. Jongbloed, MSc, PhDd and
- Katja Zeppenfeld, MD, PhDa,∗ ()
- aDepartment of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
- bDepartment of Clinical Genetics, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands
- cDepartment of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands
- dDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
- ↵∗Address for correspondence:
Dr. Katja Zeppenfeld, Leiden University Medical Center, Department of Cardiology (C-05-P), P.O. Box 9600, 2300 RC Leiden, the Netherlands.
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%]), TTN (n = 6 of 37, [16%]), PLN (n = 6 of 37, [16%]), SCN5A (n = 3 of 37, [8%]), RBM20 (n = 2/37, [5%]) and DSP (n = 2 of 37, [5%]). LP/Pv+ carriers had lower 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 (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/cm2 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 lower 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.
- catheter ablation
- dilated cardiomyopathy
- genetic mutation
- genetic testing
- genetic variant
- inherited cardiomyopathy
- nonischemic cardiomyopathy
- ventricular tachycardia
This work was supported by the Dutch Heart Foundation (CVON2015-12 eDETECT and 2018-30 PREDICT [to Dr. van Tintelen]). The Department of Cardiology Leiden has received research and fellowship grants from Edward Lifesciences, Boston Scientific, Medtronic, Biotronik, and Biosense Webster. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Clinical Electrophysiology author instructions page.
- Received January 3, 2020.
- Revision received April 13, 2020.
- Accepted April 20, 2020.
- 2020 American College of Cardiology Foundation
This article requires a subscription or purchase to view the full text. If you are a subscriber or member, click Login or the Subscribe link (top menu above) to access this article.