TY - JOUR
T1 - Prevalence and Prognostic Impact of Pathogenic Variants in Patients With Dilated Cardiomyopathy Referred for Ventricular Tachycardia Ablation
AU - Ebert, Micaela
AU - Wijnmaalen, Adrianus P.
AU - de Riva, Marta
AU - Trines, Serge A.
AU - Androulakis, Alexander F.A.
AU - Glashan, Claire A.
AU - Schalij, Martin J.
AU - Peter van Tintelen, J.
AU - Jongbloed, Jan D.H.
AU - Zeppenfeld, Katja
N1 - Funding Information:
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.
Publisher Copyright:
© 2020 American College of Cardiology Foundation
PY - 2020/9
Y1 - 2020/9
N2 - 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.
AB - 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.
KW - catheter ablation
KW - dilated cardiomyopathy
KW - genetic mutation
KW - genetic testing
KW - genetic variant
KW - inherited cardiomyopathy
KW - nonischemic cardiomyopathy
KW - ventricular tachycardia
UR - http://www.scopus.com/inward/record.url?scp=85089376577&partnerID=8YFLogxK
U2 - 10.1016/j.jacep.2020.04.025
DO - 10.1016/j.jacep.2020.04.025
M3 - Article
C2 - 32972544
AN - SCOPUS:85089376577
SN - 2405-500X
VL - 6
SP - 1103
EP - 1114
JO - JACC: Clinical Electrophysiology
JF - JACC: Clinical Electrophysiology
IS - 9
ER -