Cited 1 times since 2020 (1.3 per year) source: Scopus JACC. Clinical electrophysiology, Volume 6, Issue 9, 29 5 2020, Pages 1103-1114 Prevalence and Prognostic Impact of Pathogenic Variants in Patients With Dilated Cardiomyopathy Referred for Ventricular Tachycardia Ablation. Ebert M, Wijnmaalen AP, de Riva M, Trines SA, Androulakis AFA, Glashan CA, Schalij MJ, Peter van Tintelen J, Jongbloed JDH, Zeppenfeld K

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 of 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 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/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.

Keywords: Genetic mutation, Dilated cardiomyopathy, Catheter ablation, Ventricular tachycardia, Genetic Testing, Genetic Variant, Nonischemic Cardiomyopathy, Inherited Cardiomyopathy

JACC Clin Electrophysiol. 2020 7;6(9):1103-1114