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Catheter ablation of arrhythmogenic right ventricular cardiomyopathy ventricular tachycardia: 18-year experience in 284 patients

Catheter ablation of arrhythmogenic right ventricular cardiomyopathy ventricular tachycardia:... Abstract Aims The study aims to describe the long-term outcome of radiofrequency catheter ablation for ventricular tachycardia (VT) in a large cohort arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. Methods and results Radiofrequency catheter ablation was performed in 284 ARVC patients due to VT between July 2000 and January 2019. An endocardial approach was used initially, with epicardial ablation procedures reserved for those patients who failed an endocardial ablation. Activation, entrainment, pace and substrate mapping strategies were used with regional ablation applied. A total of 393 ablation procedures were performed including endocardial approach only (n = 377) and endo and epicardial combined (n = 16). Right ventricular basal free wall was accounted as the primary substrate of VT in 258 (65.6%) patients. There were 81 patients underwent redo ablation procedure (second time = 81; ≥3 times = 28). New targets were observed in 68.8% of redo procedures. There were 171 VT recurrences and 19 deaths occurred during the follow-up. Ventricular tachycardia-free survival rate of the first, second, and last ablation procedure was 56.7%, 73.2%, and 78.1%, respectively. Multivariate analysis showed ≥3 induced VTs in the procedure was correlated with rehospitalized VT recurrence [hazard ratio (HR) 1.467, 95% confidence interval (CI) 1.052–2.046; P = 0.024]. For all-cause mortality, rehospitalized VT and ≥3 induced VTs were the independent risk factors (HR 2.954, 95% CI 1.8068.038; P = 0.034; HR 3.189, 95% CI 1.073–9.482; P = 0.037). Conclusion Endocardial ablation is effective to ARVC VT though it may require repeated procedures. Induced multiple VTs was correlated with worse outcomes. Arrhythmogenic right ventricular cardiomyopathy, Catheter ablation, Ventricular tachycardia, Prognosis What’s new? This retrospective study proves the safety and efficacy of repeated endocardial ablation for arrhythmogenic right ventricular cardiomyopathy and ventricular tachycardia (VT). More than or equal to 3 induced VTs in the procedure was correlated with rehospitalized VT recurrence. Rehospitalized VT and ≥3 induced VTs were the independent risk factors. For patients underwent VT recurrence and repeated electrophysiological procedures, new ablation targets were observed in 68.8%. Introduction Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy with high incidence of ventricular tachycardia (VT), which may cause sudden cardiac death.1,2 Progressive fibrofatty replacement is the pathological hallmark of ARVC and provides the substrate for ventricular arrhythmias.3 Catheter ablation of VT is an important therapeutic option for patients with ARVC,4,5 particularly in young patients. The main rationale for VT ablation at present is to improve quality of life, as no study has shown that VT ablation reduces mortality.4,6–13 Data regarding long-term follow-up after ablation are limited. The objectives of this study were to determine the long-term efficacy of catheter ablation for ARVC–VT and to identify predictors of VT recurrence and all-cause mortality. Methods Study population From July 2000 to March 2019, 284 ARVC patients who underwent catheter ablation for treatment of VT were consecutively enrolled. Every patient had at least one recurrence of sustained VT despite treatment with a membrane active antiarrhythmic medication. All patients met the 2010 diagnostic criteria for ARVC.14 Implantable cardioverter-defibrillator (ICD) implantation was advised for all indicated patients. Informed consent was obtained from all patients. The study was approved by the institutional ethics committee. Electrophysiology and catheter ablation The antiarrhythmic drugs were discontinued for at least five half-lives before the procedure. The electrophysiological testing protocol has been reported previously.7,15,16 All of the subjects were studied in the post-absorptive state under conscious sedation. Right ventricular (RV) geometry was built using Ensite Array/NavX (St Jude Medical, St Paul, MN, USA) or CARTO system (Biosense Webster). Ventricular tachycardia was induced according to standard programmed stimulation up to three ventricular extra stimuli until reaching ventricular refractoriness at two sites and burst ventricular pacing (cycle length ≤ 200 ms) if necessary. Intravenous isoproterenol was used (maximum dose, 6 µg/min) when needed. Activation mapping of VT was always performed when non-contact array was used (before 2012), especially in patients with haemodynamically unstable VT. In patients with haemodynamically tolerated and sustained VT, both activation and entrainment mapping would be performed. Pace mapping was performed if the VT is unstable or not inducible but recorded by a 12-lead electrocardiogram, and the ablation would be guided on the basis of detailed characterization of the substrate mapping (split or delayed potentials, discrete higher-voltage channels in the low-voltage region).17 An endocardial approach was used initially, with epicardial ablation procedures reserved for those patients who failed an endocardial ablation. Epicardial access was obtained from subxiphoid area under the guide of X-ray since 2014.18 An 8.5-Fr steerable sheath (Agilis, St Jude Medical, St Paul, MN, USA) was introduced to the epicardium. Deca-polar steerable catheter or ablation catheter was used to conduct activation or substrate mapping. Among the 284 patients in this series, 271 patients underwent only an endocardial approach, 8 patients underwent an endocardial and epicardial approach at the same session, and 5 patients underwent an initial endocardial approach with a separate epicardial VT ablation performed one or more weeks later. Regional ablation strategy was applied in all cases by using irrigated catheter at the target sites based on mapping findings with the upper power limits of 30–40 W and temperature limit of 45°C.7 Acute success is defined as no inducibility of any sustained ventricular arrhythmias at two different points despite a complete stimulation protocol for at least three times. Induced VT with similar morphology but a slower rate (with cycle length 30% longer and ≤160 b.p.m.) was defined as partial success. Substrate modification is defined as, in case of non-induction and unmappable VT, the abolishment of all delayed and/or fractioned potentials. Follow-up Patients’ follow-up was carried out every 6 months after discharge via telephone or outpatient visit. For the 41 patients with an ICD, ICD interrogations were conducted every 3–6 months in the device clinic. The primary endpoint of this study was freedom from death or cardiac transplantation. Another endpoint was the recurrence of sustained VT and/or appropriate ICD therapy. Follow-up data after the last procedure were reported for whom underwent multiple procedures. Statistical analyses Statistical analyses were performed using SPSS 20.0 software (SPSS Inc., Chicago, IL, USA). Continuous variables were presented as mean ± standard deviation or median (range). Categorical variables were presented as frequencies and percentages. The Mann–Whitney U and Kruskal–Wallis H tests were used to compare continuous variables between groups if the variable was not normally distributed. The χ2 analysis was used to compare the categorical variables between groups. Cox regression analyses were performed to evaluate predictors associated with the long-term endpoint outcomes. The following variables including age, gender and parameters of 2D ultrasound, and diagnostic category were analysed. All tests were two-tailed and a statistical significance was established at a P < 0.05. Results Study population There were 284 consecutive patients (231 male) with average age 38.2 ± 13.3 (14–76) years enrolled. The clinical characteristics are listed in Table 1. The age of symptom onset was 34.1 ± 13.2 years. More than half of the patients [155 (54.6%)] presented before 35 years’ old. The most common symptom was palpitation which was complained by 169 (59.5%) patients. Before the primary ablation, there were 155 (54.6%) patients who presented with a history of syncope and 92 (32.4%) patients had a cardiac arrest and cardiopulmonary resuscitation. Left ventricular ejection fraction <50% detected using transthoracic echocardiography and magnetic resonance imaging was observed in 28 patients. The rate of clinical VT reached 188.8 ± 42.3 b.p.m. Genetic data were available for 119 patients of whom 86 patients showed pathogenic desmosomal mutations. Table 1 Baseline characteristics of the study cohort (n = 284) Age (years), mean ± SD 38.2 ± 13.3 Male, n (%) 231 (81.3) Syncope, n (%) 159 (53) BMI (kg/m2), mean ± SD 23.8 ± 3.5 Rate of clinical VT (b.p.m.), mean ± SD 188.8 ± 42.3 Initial symptoms, n (%)  Palpitation 169 (59.2)  Syncope 155 (54.6)  Presyncope 28 (10.0) TTE  RV dilation, n (%) 98 (34.5)  LV dimension (mm), mean ± SD 47.5 ± 5.6  LVEF (%), mean ± SD 60.8 ± 8.7 Comorbidity, n (%)  Diabetes mellitus 10 (3.5)  Hypertension 30 (10.6)  Hyperlipidaemia 17 (6.0) NYHA, n (%)  I 247 (87.0)  II 33 (11.6)  III 1 (0.3)  IV 0 (0.0) Pathogenic mutation, n (%)  PKP2 53 (18.7)  DSG-2 21 (7.4)  DSC-2 6 (2.1)  DSP 6 (2.1) Global or regional dysfunction and structural alterations, n (%)  Major 101 (35.6)  Minor 35 (12.3) Tissue characterization of wall, n (%)  Major 5 (1.8)  Minor 0 (0.0) Repolarization abnormalities, n (%)  Major 124 (43.7)  Minor 34 (12.0) Depolarization/conduction abnormalities, n (%)  Major 36 (12.7)  Minor 47 (16.5) Arrhythmias, n (%)  Major 259 (92.0)  Minor 25 (8.8) Family history, n (%)  Major 56 (19.7)  Minor 4 (1.4) Medicines at discharge, n (%)  β-Blocker 55 (19.4)  Mexiletine 9 (3.2)  Propafenone 20 (7.0)  Sotalol 163 (57.4)  Amiodarone 22 (7.7) Age (years), mean ± SD 38.2 ± 13.3 Male, n (%) 231 (81.3) Syncope, n (%) 159 (53) BMI (kg/m2), mean ± SD 23.8 ± 3.5 Rate of clinical VT (b.p.m.), mean ± SD 188.8 ± 42.3 Initial symptoms, n (%)  Palpitation 169 (59.2)  Syncope 155 (54.6)  Presyncope 28 (10.0) TTE  RV dilation, n (%) 98 (34.5)  LV dimension (mm), mean ± SD 47.5 ± 5.6  LVEF (%), mean ± SD 60.8 ± 8.7 Comorbidity, n (%)  Diabetes mellitus 10 (3.5)  Hypertension 30 (10.6)  Hyperlipidaemia 17 (6.0) NYHA, n (%)  I 247 (87.0)  II 33 (11.6)  III 1 (0.3)  IV 0 (0.0) Pathogenic mutation, n (%)  PKP2 53 (18.7)  DSG-2 21 (7.4)  DSC-2 6 (2.1)  DSP 6 (2.1) Global or regional dysfunction and structural alterations, n (%)  Major 101 (35.6)  Minor 35 (12.3) Tissue characterization of wall, n (%)  Major 5 (1.8)  Minor 0 (0.0) Repolarization abnormalities, n (%)  Major 124 (43.7)  Minor 34 (12.0) Depolarization/conduction abnormalities, n (%)  Major 36 (12.7)  Minor 47 (16.5) Arrhythmias, n (%)  Major 259 (92.0)  Minor 25 (8.8) Family history, n (%)  Major 56 (19.7)  Minor 4 (1.4) Medicines at discharge, n (%)  β-Blocker 55 (19.4)  Mexiletine 9 (3.2)  Propafenone 20 (7.0)  Sotalol 163 (57.4)  Amiodarone 22 (7.7) Genetic data were available for 119 patients. BMI, body mass index; DSC-2, desmocollin-2; DSG-2, desmoglein-2; DSP, desmoplakin; LV dimension, left ventricular dimension; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; PKP2, plakophilin-2 gene; RV dilation, right ventricular dilation; SD, standard deviation; TTE, transthoracic echocardiography; VT, ventricular tachycardia. Open in new tab Table 1 Baseline characteristics of the study cohort (n = 284) Age (years), mean ± SD 38.2 ± 13.3 Male, n (%) 231 (81.3) Syncope, n (%) 159 (53) BMI (kg/m2), mean ± SD 23.8 ± 3.5 Rate of clinical VT (b.p.m.), mean ± SD 188.8 ± 42.3 Initial symptoms, n (%)  Palpitation 169 (59.2)  Syncope 155 (54.6)  Presyncope 28 (10.0) TTE  RV dilation, n (%) 98 (34.5)  LV dimension (mm), mean ± SD 47.5 ± 5.6  LVEF (%), mean ± SD 60.8 ± 8.7 Comorbidity, n (%)  Diabetes mellitus 10 (3.5)  Hypertension 30 (10.6)  Hyperlipidaemia 17 (6.0) NYHA, n (%)  I 247 (87.0)  II 33 (11.6)  III 1 (0.3)  IV 0 (0.0) Pathogenic mutation, n (%)  PKP2 53 (18.7)  DSG-2 21 (7.4)  DSC-2 6 (2.1)  DSP 6 (2.1) Global or regional dysfunction and structural alterations, n (%)  Major 101 (35.6)  Minor 35 (12.3) Tissue characterization of wall, n (%)  Major 5 (1.8)  Minor 0 (0.0) Repolarization abnormalities, n (%)  Major 124 (43.7)  Minor 34 (12.0) Depolarization/conduction abnormalities, n (%)  Major 36 (12.7)  Minor 47 (16.5) Arrhythmias, n (%)  Major 259 (92.0)  Minor 25 (8.8) Family history, n (%)  Major 56 (19.7)  Minor 4 (1.4) Medicines at discharge, n (%)  β-Blocker 55 (19.4)  Mexiletine 9 (3.2)  Propafenone 20 (7.0)  Sotalol 163 (57.4)  Amiodarone 22 (7.7) Age (years), mean ± SD 38.2 ± 13.3 Male, n (%) 231 (81.3) Syncope, n (%) 159 (53) BMI (kg/m2), mean ± SD 23.8 ± 3.5 Rate of clinical VT (b.p.m.), mean ± SD 188.8 ± 42.3 Initial symptoms, n (%)  Palpitation 169 (59.2)  Syncope 155 (54.6)  Presyncope 28 (10.0) TTE  RV dilation, n (%) 98 (34.5)  LV dimension (mm), mean ± SD 47.5 ± 5.6  LVEF (%), mean ± SD 60.8 ± 8.7 Comorbidity, n (%)  Diabetes mellitus 10 (3.5)  Hypertension 30 (10.6)  Hyperlipidaemia 17 (6.0) NYHA, n (%)  I 247 (87.0)  II 33 (11.6)  III 1 (0.3)  IV 0 (0.0) Pathogenic mutation, n (%)  PKP2 53 (18.7)  DSG-2 21 (7.4)  DSC-2 6 (2.1)  DSP 6 (2.1) Global or regional dysfunction and structural alterations, n (%)  Major 101 (35.6)  Minor 35 (12.3) Tissue characterization of wall, n (%)  Major 5 (1.8)  Minor 0 (0.0) Repolarization abnormalities, n (%)  Major 124 (43.7)  Minor 34 (12.0) Depolarization/conduction abnormalities, n (%)  Major 36 (12.7)  Minor 47 (16.5) Arrhythmias, n (%)  Major 259 (92.0)  Minor 25 (8.8) Family history, n (%)  Major 56 (19.7)  Minor 4 (1.4) Medicines at discharge, n (%)  β-Blocker 55 (19.4)  Mexiletine 9 (3.2)  Propafenone 20 (7.0)  Sotalol 163 (57.4)  Amiodarone 22 (7.7) Genetic data were available for 119 patients. BMI, body mass index; DSC-2, desmocollin-2; DSG-2, desmoglein-2; DSP, desmoplakin; LV dimension, left ventricular dimension; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; PKP2, plakophilin-2 gene; RV dilation, right ventricular dilation; SD, standard deviation; TTE, transthoracic echocardiography; VT, ventricular tachycardia. Open in new tab Implantable cardioverter-defibrillator was implanted in 41 (14.4%) patients, 12 (29.3%) of whom after the first ablation procedure. The indication for ICD implantation was documented sustained VT in 17 patients and sudden cardiac death in 24 patients. Patients refused ICD implantation mainly due to economic considerations and but also due to fear of inappropriate ICD discharge. A total of 67 prior catheter ablation procedures were performed in 63 patients before being referred to our centre. Electrophysiology and catheter ablation Totally, 393 catheter ablation procedures (endocardium only = 377, endo-epicardium = 16) were conducted, of which, 158 patients underwent a single procedure with the rest of 2.5 ± 0.7 procedures. Characteristics of the electrophysiological study were shown in Table 2. Ventricular tachycardia was induced in 310 (78.9%) with median 2 VTs [range (1–11)] per procedure. Non-mappable VT occurred in 67 (16.4%) procedures (non-sustained VT = 15, syncope = 52). The rate of mappable VT reached 209.4 ± 38.0 b.p.m. Ventricular fibrillation was induced or deteriorated from VT in 13 (3.2%) procedures. Left bundle branch block with superior axis was the most common types [induced in 291procedures (74.0%); median type: 1 (0–7); average rate: 207.6 ± 39.9 b.p.m.]. Table 2 Electrophysiological findings in the procedures (n = 393) VTs in the procedure  0 82  1 123  2 82  3 53  4 22  5 14  ≥6 16 Syncope, n (%) 55 (14.0) Mappable VT  LBBB with superior axis, n (%) 293 (74.5%)   Types, median (range) 1 (1–7)   Rate (b.p.m.), mean ± SD 207.6 ± 40.0  LBBB with inferior axis, n (%) 59 (15.0)   Types, median (range) 1 (1–3)   Rate (b.p.m.), mean ± SD 209.8 ± 67.5  RBBB with superior axis, n (%) 26 (6.6%)   Types, median (range) 1 (1–3)   Rate (b.p.m.), mean ± SD 210.5 ± 60.2  RBBB with inferior axis, n (%) 6 (1.5%)   Types 1   Rate (b.p.m.), mean ± SD 225.8 ± 60.0 VTs in the procedure  0 82  1 123  2 82  3 53  4 22  5 14  ≥6 16 Syncope, n (%) 55 (14.0) Mappable VT  LBBB with superior axis, n (%) 293 (74.5%)   Types, median (range) 1 (1–7)   Rate (b.p.m.), mean ± SD 207.6 ± 40.0  LBBB with inferior axis, n (%) 59 (15.0)   Types, median (range) 1 (1–3)   Rate (b.p.m.), mean ± SD 209.8 ± 67.5  RBBB with superior axis, n (%) 26 (6.6%)   Types, median (range) 1 (1–3)   Rate (b.p.m.), mean ± SD 210.5 ± 60.2  RBBB with inferior axis, n (%) 6 (1.5%)   Types 1   Rate (b.p.m.), mean ± SD 225.8 ± 60.0 LBBB, left bundle branch block; RBBB, right bundle branch block; SD, standard deviation; VTs, ventricular tachycardias. Open in new tab Table 2 Electrophysiological findings in the procedures (n = 393) VTs in the procedure  0 82  1 123  2 82  3 53  4 22  5 14  ≥6 16 Syncope, n (%) 55 (14.0) Mappable VT  LBBB with superior axis, n (%) 293 (74.5%)   Types, median (range) 1 (1–7)   Rate (b.p.m.), mean ± SD 207.6 ± 40.0  LBBB with inferior axis, n (%) 59 (15.0)   Types, median (range) 1 (1–3)   Rate (b.p.m.), mean ± SD 209.8 ± 67.5  RBBB with superior axis, n (%) 26 (6.6%)   Types, median (range) 1 (1–3)   Rate (b.p.m.), mean ± SD 210.5 ± 60.2  RBBB with inferior axis, n (%) 6 (1.5%)   Types 1   Rate (b.p.m.), mean ± SD 225.8 ± 60.0 VTs in the procedure  0 82  1 123  2 82  3 53  4 22  5 14  ≥6 16 Syncope, n (%) 55 (14.0) Mappable VT  LBBB with superior axis, n (%) 293 (74.5%)   Types, median (range) 1 (1–7)   Rate (b.p.m.), mean ± SD 207.6 ± 40.0  LBBB with inferior axis, n (%) 59 (15.0)   Types, median (range) 1 (1–3)   Rate (b.p.m.), mean ± SD 209.8 ± 67.5  RBBB with superior axis, n (%) 26 (6.6%)   Types, median (range) 1 (1–3)   Rate (b.p.m.), mean ± SD 210.5 ± 60.2  RBBB with inferior axis, n (%) 6 (1.5%)   Types 1   Rate (b.p.m.), mean ± SD 225.8 ± 60.0 LBBB, left bundle branch block; RBBB, right bundle branch block; SD, standard deviation; VTs, ventricular tachycardias. Open in new tab Table 3 Related factors of VT recurrence . Univariate analysis . P-value . Multivariate analysis . P-value . HR (95% CI) . HR (95% CI) . Gender 0.699 (0.454–1.078) 0.105 0.685 (0.444–1.057) 0.088 Age 0.994 (0.983–1.006) 0.327 0.994 (0.982–1.005) 0.295 With activation mapping 1.290 (0.855–1.947) 0.225 1.120 (0.724–2.046) 0.611 VTs (≥3) 1.482 (1.083–2.027) 0.007 1.467 (1.052–2.046) 0.024 . Univariate analysis . P-value . Multivariate analysis . P-value . HR (95% CI) . HR (95% CI) . Gender 0.699 (0.454–1.078) 0.105 0.685 (0.444–1.057) 0.088 Age 0.994 (0.983–1.006) 0.327 0.994 (0.982–1.005) 0.295 With activation mapping 1.290 (0.855–1.947) 0.225 1.120 (0.724–2.046) 0.611 VTs (≥3) 1.482 (1.083–2.027) 0.007 1.467 (1.052–2.046) 0.024 CI, confidence interval; HR, hazard ratio; VTs, ventricular tachycardias. Open in new tab Table 3 Related factors of VT recurrence . Univariate analysis . P-value . Multivariate analysis . P-value . HR (95% CI) . HR (95% CI) . Gender 0.699 (0.454–1.078) 0.105 0.685 (0.444–1.057) 0.088 Age 0.994 (0.983–1.006) 0.327 0.994 (0.982–1.005) 0.295 With activation mapping 1.290 (0.855–1.947) 0.225 1.120 (0.724–2.046) 0.611 VTs (≥3) 1.482 (1.083–2.027) 0.007 1.467 (1.052–2.046) 0.024 . Univariate analysis . P-value . Multivariate analysis . P-value . HR (95% CI) . HR (95% CI) . Gender 0.699 (0.454–1.078) 0.105 0.685 (0.444–1.057) 0.088 Age 0.994 (0.983–1.006) 0.327 0.994 (0.982–1.005) 0.295 With activation mapping 1.290 (0.855–1.947) 0.225 1.120 (0.724–2.046) 0.611 VTs (≥3) 1.482 (1.083–2.027) 0.007 1.467 (1.052–2.046) 0.024 CI, confidence interval; HR, hazard ratio; VTs, ventricular tachycardias. Open in new tab The results of substrate mapping and critical VT targets were shown in Figure 1. Right ventricular sub-tricuspid valvular regions accounted for the majority of low-voltage area, abnormal potentials and VT critical sites. Low-voltage area located mostly at the RV basal free wall (73.9%) with RV basal inferior wall, mid-lateral wall accounting for 31.4% and 32.2%, respectively. Same distributed pattern was observed in abnormal potentials. Right ventricular basal-mid lateral wall was the most commonly area detected abnormal potentials (65.5%). Right ventricular basal inferior wall, RV outflow tract (RVOT), and RV apex accounts for 33.3%, 31.3%, and 10.2%. Figure 1 Open in new tabDownload slide Distribution of substrate mapping results and critical sites of VTs. (A) Low-voltage area distribution; (B) abnormal potentials distribution; and (C) VT critical sites distribution. RV, right ventricular; RVOT, right ventricular outflow tract; VT, ventricular tachycardia. Figure 1 Open in new tabDownload slide Distribution of substrate mapping results and critical sites of VTs. (A) Low-voltage area distribution; (B) abnormal potentials distribution; and (C) VT critical sites distribution. RV, right ventricular; RVOT, right ventricular outflow tract; VT, ventricular tachycardia. Epicardial mapping was recommended when endocardial ablation failed. Four patients refused the epicardial approach due to fear of severe complications. Furthermore, two epicardial punctures failed to due to abnormal anatomy and adhesions. Five procedures showed VT targets from endocardium rather than appositional epicardial sites probably due to large dense scar of epicardium (one typical example was shown in Supplementary material online, Figure S1). Repeated electrophysiological examination was performed at the end of ablation. Acute success was reached in 276 (70.2%) procedures a partial success in 36 (9.2%). Follow-up outcomes and related risk factors Ventricular tachycardia recurrence After 46.3 ± 40.7 months’ (median 36.0) follow-up, 123 patients underwent 171 recurrences. Ventricular tachycardia-free survival rate after first, second, and last ablation procedure was 56.7%, 73.2%, and 78.1%. The survival curve free from sustained VT recurrence and/or appropriate ICD therapy was shown in Figure 2A. Univariate analysis showed induced VTs ≥3 types in the procedure correlated with VT recurrence which was adjusted by multivariate analysis [hazard ratio (HR) 1.467, 95% confidence interval (CI) 1.052–2.046; P = 0.024] (Table 3, Figure 2B). Notably, mapping strategies (with activation mapping vs. without activation mapping) were not associated with VT recurrence (HR 1.120, 95% CI 0.724–2.046; P = 0.611). Figure 2 Open in new tabDownload slide Survival curve free from VT recurrence and related factor. (A) Survival curve free from VT recurrence and (B) impact of induced VTs in the procedure. VT, ventricular tachycardia. Figure 2 Open in new tabDownload slide Survival curve free from VT recurrence and related factor. (A) Survival curve free from VT recurrence and (B) impact of induced VTs in the procedure. VT, ventricular tachycardia. Table 4 Related factors with all-cause mortality . Univariate analysis . P-value . Multivariate analysis . P-value . HR (95% CI) . HR (95% CI) . Age 0.993 (0.960–1.026) 0.673 0.984 (0.947–1.021) 0.393 Gender 1.343 (0.492–3.668) 0.565 2.338 (0.743–7.356) 0.147 LVEF<50% 3.114 (1.010–9.596) 0.048 2.473 (0.762–8.027) 0.132 Syncope during the procedure 2.793 (1.157–6.740) 0.022 1.026 (0.311–3.380) 0.967 VT recurrence 6.195 (2.566–14.956) <0.001 2.954 (1.086–8.038) 0.034 VT induced in the procedure 5.145 (2.166–12.222) <0.001 3.189 (1.073–9.482) 0.037 . Univariate analysis . P-value . Multivariate analysis . P-value . HR (95% CI) . HR (95% CI) . Age 0.993 (0.960–1.026) 0.673 0.984 (0.947–1.021) 0.393 Gender 1.343 (0.492–3.668) 0.565 2.338 (0.743–7.356) 0.147 LVEF<50% 3.114 (1.010–9.596) 0.048 2.473 (0.762–8.027) 0.132 Syncope during the procedure 2.793 (1.157–6.740) 0.022 1.026 (0.311–3.380) 0.967 VT recurrence 6.195 (2.566–14.956) <0.001 2.954 (1.086–8.038) 0.034 VT induced in the procedure 5.145 (2.166–12.222) <0.001 3.189 (1.073–9.482) 0.037 CI, confidence interval; HR, hazard ratio; LVEF, left ventricular ejection fraction; VTs, ventricular tachycardias. Open in new tab Table 4 Related factors with all-cause mortality . Univariate analysis . P-value . Multivariate analysis . P-value . HR (95% CI) . HR (95% CI) . Age 0.993 (0.960–1.026) 0.673 0.984 (0.947–1.021) 0.393 Gender 1.343 (0.492–3.668) 0.565 2.338 (0.743–7.356) 0.147 LVEF<50% 3.114 (1.010–9.596) 0.048 2.473 (0.762–8.027) 0.132 Syncope during the procedure 2.793 (1.157–6.740) 0.022 1.026 (0.311–3.380) 0.967 VT recurrence 6.195 (2.566–14.956) <0.001 2.954 (1.086–8.038) 0.034 VT induced in the procedure 5.145 (2.166–12.222) <0.001 3.189 (1.073–9.482) 0.037 . Univariate analysis . P-value . Multivariate analysis . P-value . HR (95% CI) . HR (95% CI) . Age 0.993 (0.960–1.026) 0.673 0.984 (0.947–1.021) 0.393 Gender 1.343 (0.492–3.668) 0.565 2.338 (0.743–7.356) 0.147 LVEF<50% 3.114 (1.010–9.596) 0.048 2.473 (0.762–8.027) 0.132 Syncope during the procedure 2.793 (1.157–6.740) 0.022 1.026 (0.311–3.380) 0.967 VT recurrence 6.195 (2.566–14.956) <0.001 2.954 (1.086–8.038) 0.034 VT induced in the procedure 5.145 (2.166–12.222) <0.001 3.189 (1.073–9.482) 0.037 CI, confidence interval; HR, hazard ratio; LVEF, left ventricular ejection fraction; VTs, ventricular tachycardias. Open in new tab Recurrences decreased significantly year by year (Figure 3). The median time from ablation to recurrence is 17.3 months (range 0–157.0). Totally, 99 (57.9%) recurrences occurred within 2 years. Compared with patients in whom VT recurred within 2 years, those beyond were more likely to demonstrate new VT targets (10.1% vs. 1.4%, P = 0.022) (Supplementary material online, Figure S2). The number of induced VTs in the procedure, age, gender, and the use of activation or substrate mapping were not significantly different between patients recurred within or beyond 2 years. Figure 3 Open in new tabDownload slide Patients underwent VT recurrence negatively correlated with follow-up time (r = −0.795, P = 0.006). VT, ventricular tachycardia. Figure 3 Open in new tabDownload slide Patients underwent VT recurrence negatively correlated with follow-up time (r = −0.795, P = 0.006). VT, ventricular tachycardia. Redo ablation procedures There were 109 redo ablation procedures in 81 patients (second time = 81 and equal to or more than 3 times = 28). New targets were observed in 68.8% procedures, which may be explained by the disease progression or incomplete ablation. Incidence of preprocedural syncope decrease significantly for first, second, and more than 3 times ablation procedure [155 (54.6%) vs. 13 (16.5%) vs.1 (3.6%), P < 0.001]. Ventricular tachycardia induction rate, types of VT, fastest rate of VT in the procedure, and time interval between subsequent procedures were not significantly different in the three groups (P > 0.05). All-cause mortality During follow-up time of 73.0 ± 50.1 months (median 64), 19 patients died (12 patients died of sudden cardiac death). Multivariate analysis showed VT recurrence and induced VTs ≥3 types in the procedure were associated with death (HR 2.954, 95% CI 1.806–8.038; P = 0.034; HR 3.189, 95% CI 1.073–9.482; P = 0.037) which were also significant after adjusted by age and gender (Table 4, Figure 4). Figure 4 Open in new tabDownload slide Survival curve free from death. (A) Survival curve free from death; (B) impact of VT recurrence on all-cause mortality; and (C) impact of induced VTs in the procedure on all-cause mortality. VT, ventricular tachycardia. Figure 4 Open in new tabDownload slide Survival curve free from death. (A) Survival curve free from death; (B) impact of VT recurrence on all-cause mortality; and (C) impact of induced VTs in the procedure on all-cause mortality. VT, ventricular tachycardia. Complications Right ventricular perforation was observed in one patient whose RV apex showed aneurysm in transthoracic echocardiography. The patient was stable after drainage and suffered from sudden cardiac death 1 month after discharge. There were no procedure-related deaths. Discussion Main findings This is a large cohort study aimed at evaluating the long-term prognosis of patients of VT with ARVC underwent catheter ablation. Recurrences decreased significantly according to year. Repeated endocardial ablation (combined with epicardial when necessary) was considered effective and efficacy in facilitating VT control and the reduction in the rate of recurrent syncope. Induced VTs (≥3 types) in the procedure is the major risk factor independently associated with worse outcomes. New targets were found in most of the redo procedures. Arrhythmogenic right ventricular cardiomyopathy is associated with an increased risk of sudden death.7,11 In our cohort, syncope occurred in half of the patients and two-thirds underwent cardiopulmonary resuscitation outside hospital. These patients were in intermediate- or high-risk state.8 Implantable cardioverter-defibrillator implantation is generally recommended in patients who have experienced sustained VT, cardiac syncope, and/or sudden death.3 However, due to the finical reason and the fear of inappropriate discharges, only a small number of patients received ICD implantation.7 In this study, only less than one-sixth of patients received ICD implantation. Catheter ablation was considered as an effective method to terminate VT and reduce VT burden with the successful rate more than 80% with repeated procedures.4,5,7 However, long-term (10 years) follow-up data showed VT-free survival rate dropped to 14–15%. In our study, although incidence of VT recurrence also remains high during follow-up period, redo endocardial ablation procedures may help to remain VT suppression. Studies demonstrated that disease progression or the progressively pathological replacement of myocytes considered as one of the characteristics of ARVC which may cause VT recurrence.4 Similar to the prior studies, new critical VT targets were observed in most redo procedures. Furthermore, this study found that those recurrent beyond 2 years were more likely to demonstrate new VT targets. The median number of VTs induced during the baseline electrophysiology study was 2. Unmappable VTs (non-sustained VT, haemodynamical unstable, and deteriorating to ventricular fibrillation) occurred in one-third of the procedures. For patients with unmappable VT, substrate mapping was proved to be an effective method.19 In this study, multivariate analysis showed mapping strategy (with or without activation) was not associated with VT recurrence. In addition, for the mappable VTs, the most common targets were sub-tricuspid valvular regions, followed by RVOT and RV apical region. The same distributed pattern was also observed in the substrate mapping results, which demonstrates substrate mapping may be considered as an important alternative method. Furthermore, this study demonstrates that VTs induced in the procedure was correlated with worse outcomes. For these patients, ICD implantation was strongly recommended. Epicardial ablation has been reported to result in higher VT-free survival rates than endocardial ablation.12 The mapping results showed low bipolar voltage area is more widely spread in the epicardium than that of endocardium especially for patients with minimal RV structural changes and for those with limited endocardial abnormal substrate and/or failed prior endocardial ablation.5 However, large dense scar of epicardium without satisfied potential, in which cases VT terminated in the endocardium, also happened. What’s more, complications regarding the epicardial procedure were very high. Although complications of epicardial puncture (RV puncture) might be mitigated using coronary vein exit and carbon dioxide insufflation,20 coronary artery injury, pericardial inflammatory reaction, and other complications cannot be avoided. In our study, some of the patients even refused to choose epicardial puncture for fear of the related complications. On the other hand, it is also happened that failure to find satisfying targets from epicardium due to large low-voltage area and dense scar. Studies have demonstrated endocardial procedures may reflect and eliminate epicardial local abnormal ventricular activity.13 Data from our study demonstrate that endocardial ablation and appropriate epicardial ablation demonstrates favourable results. In our centre, ablation was performed via epicardial access only when endocardial ablation failed or no abnormal pace or substrate mapping targets was found intracardially. Ventricular tachycardias ≥3 strongly indicates worse follow-up outcome irrespective of ablation access and acute procedure endpoints. Careful endocardial mapping should be a prior consideration with epicardial access chosen as an alternative method. Study limitations There exist limitations. Firstly, time span of 18 years indicates the strategy of mapping and ablation evolved significantly which may have an influence on the interpretation of the results. What’s more, related factors combining clinical data were included to analyse rather than genetic testing which might provide more information on the results of catheter ablation. Thirdly, there were only 41 patients underwent ICD implantation which may underestimate the recurrence rate of VT. Conclusions In conclusion, in this large cohort study, most of the patients with ARVC and VT were in intermediate or high risk of sudden cardiac death state. The majority of the patients chose catheter ablation as the first choice. Endocardial and/or epicardial ablation achieved relatively high survival rate free from VT recurrence and death. Induced VTs ≥3 in one procedure was shown to be related risk factors with worse outcomes. Acknowledgements We are indebted to Professor Hugh Calkins who reviewed the manuscript. Funding This work was supported by the National Key R&D Program of China (2017YFC1307800), Beijing Municipal Science and Technology Commission (Z161100000516022), and National Natural Science Foundation (81570309). Conflict of interest: none declared. References 1 Corrado D , Fontaine G, Marcus FI, McKenna WJ, Nava A, Thiene G et al. Arrhythmogenic right ventricular dysplasia/cardiomyopathy: need for an international registry. Study Group on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy of the Working Groups on Myocardial and Pericardial Disease and Arrhythmias of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the World Heart Federation . Circulation 2000 ; 101 : E101 – 6 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Cappelletto C , Stolfo D, De Luca A, Pinamonti B, Barbati G, Pivetta A et al. Lifelong arrhythmic risk stratification in arrhythmogenic right ventricular cardiomyopathy: distribution of events and impact of periodical reassessment . Europace 2018 ; 20 : f20 – 9 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Corrado D , Wichter T, Link MS, Hauer R, Marchlinski F, Anastasakis A et al. Treatment of arrhythmogenic right ventricular cardiomyopathy/dysplasia: an international task force consensus statement . Eur Heart J 2015 ; 36 : 3227 – 37 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Souissi Z , Boule S, Hermida JS, Doucy A, Mabo P, Pavin D et al. Catheter ablation reduces ventricular tachycardia burden in patients with arrhythmogenic right ventricular cardiomyopathy: insights from a North-Western French Multicentre Registry . Europace 2018 ; 20 : 362 – 9 . Google Scholar Crossref Search ADS PubMed WorldCat 5 Kirubakaran S , Bisceglia C, Silberbauer J, Oloriz T, Santagostino G, Yamase M et al. Characterization of the arrhythmogenic substrate in patients with arrhythmogenic right ventricular cardiomyopathy undergoing ventricular tachycardia ablation . Europace 2017 ; 19 : 1049 – 62 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Fontaine G , Frank R, Rougier I, Tonet JL, Gallais Y, Fareno G et al. Electrode catheter ablation of resistant ventricular tachycardia in arrhythmogenic right ventricular dysplasia: experience of 13 patients with a mean follow-up of 45 months . Eur Heart J 1989 ; 10 : 74 – 81 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Yao Y , Zhang S, He DS, Zhang K, Hua W, Chu J et al. Radiofrequency ablation of the ventricular tachycardia with arrhythmogenic right ventricular cardiomyopathy using non-contact mapping . Pacing Clin Electrophysiol 2007 ; 30 : 526 – 33 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Calkins H , Corrado D, Marcus F. Risk stratification in arrhythmogenic right ventricular cardiomyopathy . Circulation 2017 ; 136 : 2068 – 82 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Garcia FC , Bazan V, Zado ES, Ren JF, Marchlinski FE. Epicardial substrate and outcome with epicardial ablation of ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy/dysplasia . Circulation 2009 ; 120 : 366 – 75 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Jais P , Maury P, Khairy P, Sacher F, Nault I, Komatsu Y et al. Elimination of local abnormal ventricular activities: a new end point for substrate modification in patients with scar-related ventricular tachycardia . Circulation 2012 ; 125 : 2184 – 96 . Google Scholar Crossref Search ADS PubMed WorldCat 11 Marchlinski FE , Zado E, Dixit S, Gerstenfeld E, Callans DJ, Hsia H et al. Electroanatomic substrate and outcome of catheter ablative therapy for ventricular tachycardia in setting of right ventricular cardiomyopathy . Circulation 2004 ; 110 : 2293 – 8 . Google Scholar Crossref Search ADS PubMed WorldCat 12 Berruezo A , Acosta J, Fernandez-Armenta J, Pedrote A, Barrera A, Arana-Rueda E et al. Safety, long-term outcomes and predictors of recurrence after first-line combined endoepicardial ventricular tachycardia substrate ablation in arrhythmogenic cardiomyopathy. Impact of arrhythmic substrate distribution pattern. A prospective multicentre study . Europace 2017 ; 19 : 607 – 16 . Google Scholar Crossref Search ADS PubMed WorldCat 13 Komatsu Y , Daly M, Sacher F, Cochet H, Denis A, Derval N et al. Endocardial ablation to eliminate epicardial arrhythmia substrate in scar-related ventricular tachycardia . J Am Coll Cardiol 2014 ; 63 : 1416 – 26 . Google Scholar Crossref Search ADS PubMed WorldCat 14 Marcus FI , McKenna WJ, Sherrill D, Basso C, Bauce B, Bluemke DA et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria . Eur Heart J 2010 ; 31 : 806 – 14 . Google Scholar Crossref Search ADS PubMed WorldCat 15 Bao J , Wang J, Yao Y, Wang Y, Fan X, Sun K et al. Correlation of ventricular arrhythmias with genotype in arrhythmogenic right ventricular cardiomyopathy . Circ Cardiovasc Genet 2013 ; 6 : 552 – 6 . Google Scholar Crossref Search ADS PubMed WorldCat 16 Wu LM , Bao JR, Yao Y, Hou BB, Zheng LH, Zhang S. Fast rate (≥250 beats/min) right ventricular burst stimulation is useful for ventricular tachycardia induction in arrhythmogenic right ventricular cardiomyopathy . J Geriatr Cardiol 2016 ; 13 : 70 – 4 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 17 Komatsu Y , Daly M, Sacher F, Derval N, Pascale P, Roten L et al. Electrophysiologic characterization of local abnormal ventricular activities in postinfarction ventricular tachycardia with respect to their anatomic location . Heart Rhythm 2013 ; 10 : 1630 – 7 . Google Scholar Crossref Search ADS PubMed WorldCat 18 Sosa E , Scanavacca M, D'Avila A, Pilleggi E. A new technique to perform epicardial mapping in the electrophysiology laboratory . J Cardiovasc Electrophysiol 1996 ; 7 : 531 – 6 . Google Scholar Crossref Search ADS PubMed WorldCat 19 Corrado D , Basso C, Leoni L, Tokajuk B, Turrini P, Bauce B et al. Three-dimensional electroanatomical voltage mapping and histologic evaluation of myocardial substrate in right ventricular outflow tract tachycardia . J Am Coll Cardiol 2008 ; 51 : 731 – 9 . Google Scholar Crossref Search ADS PubMed WorldCat 20 Silberbauer J , Gomes J, O’Nunain S, Kirubakaran S, Hildick-Smith D, McCready J. Coronary vein exit and carbon dioxide insufflation to facilitate subxiphoid epicardial access for ventricular mapping and ablation: first experience . JACC Clin Electrophysiol 2017 ; 3 : 514 – 21 . Google Scholar Crossref Search ADS PubMed WorldCat Author notes " Erpeng Liang, LingminWu and Siyang Fan contributed equally to this work. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Europace Oxford University Press

Catheter ablation of arrhythmogenic right ventricular cardiomyopathy ventricular tachycardia: 18-year experience in 284 patients

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Oxford University Press
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.
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Abstract

Abstract Aims The study aims to describe the long-term outcome of radiofrequency catheter ablation for ventricular tachycardia (VT) in a large cohort arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. Methods and results Radiofrequency catheter ablation was performed in 284 ARVC patients due to VT between July 2000 and January 2019. An endocardial approach was used initially, with epicardial ablation procedures reserved for those patients who failed an endocardial ablation. Activation, entrainment, pace and substrate mapping strategies were used with regional ablation applied. A total of 393 ablation procedures were performed including endocardial approach only (n = 377) and endo and epicardial combined (n = 16). Right ventricular basal free wall was accounted as the primary substrate of VT in 258 (65.6%) patients. There were 81 patients underwent redo ablation procedure (second time = 81; ≥3 times = 28). New targets were observed in 68.8% of redo procedures. There were 171 VT recurrences and 19 deaths occurred during the follow-up. Ventricular tachycardia-free survival rate of the first, second, and last ablation procedure was 56.7%, 73.2%, and 78.1%, respectively. Multivariate analysis showed ≥3 induced VTs in the procedure was correlated with rehospitalized VT recurrence [hazard ratio (HR) 1.467, 95% confidence interval (CI) 1.052–2.046; P = 0.024]. For all-cause mortality, rehospitalized VT and ≥3 induced VTs were the independent risk factors (HR 2.954, 95% CI 1.8068.038; P = 0.034; HR 3.189, 95% CI 1.073–9.482; P = 0.037). Conclusion Endocardial ablation is effective to ARVC VT though it may require repeated procedures. Induced multiple VTs was correlated with worse outcomes. Arrhythmogenic right ventricular cardiomyopathy, Catheter ablation, Ventricular tachycardia, Prognosis What’s new? This retrospective study proves the safety and efficacy of repeated endocardial ablation for arrhythmogenic right ventricular cardiomyopathy and ventricular tachycardia (VT). More than or equal to 3 induced VTs in the procedure was correlated with rehospitalized VT recurrence. Rehospitalized VT and ≥3 induced VTs were the independent risk factors. For patients underwent VT recurrence and repeated electrophysiological procedures, new ablation targets were observed in 68.8%. Introduction Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy with high incidence of ventricular tachycardia (VT), which may cause sudden cardiac death.1,2 Progressive fibrofatty replacement is the pathological hallmark of ARVC and provides the substrate for ventricular arrhythmias.3 Catheter ablation of VT is an important therapeutic option for patients with ARVC,4,5 particularly in young patients. The main rationale for VT ablation at present is to improve quality of life, as no study has shown that VT ablation reduces mortality.4,6–13 Data regarding long-term follow-up after ablation are limited. The objectives of this study were to determine the long-term efficacy of catheter ablation for ARVC–VT and to identify predictors of VT recurrence and all-cause mortality. Methods Study population From July 2000 to March 2019, 284 ARVC patients who underwent catheter ablation for treatment of VT were consecutively enrolled. Every patient had at least one recurrence of sustained VT despite treatment with a membrane active antiarrhythmic medication. All patients met the 2010 diagnostic criteria for ARVC.14 Implantable cardioverter-defibrillator (ICD) implantation was advised for all indicated patients. Informed consent was obtained from all patients. The study was approved by the institutional ethics committee. Electrophysiology and catheter ablation The antiarrhythmic drugs were discontinued for at least five half-lives before the procedure. The electrophysiological testing protocol has been reported previously.7,15,16 All of the subjects were studied in the post-absorptive state under conscious sedation. Right ventricular (RV) geometry was built using Ensite Array/NavX (St Jude Medical, St Paul, MN, USA) or CARTO system (Biosense Webster). Ventricular tachycardia was induced according to standard programmed stimulation up to three ventricular extra stimuli until reaching ventricular refractoriness at two sites and burst ventricular pacing (cycle length ≤ 200 ms) if necessary. Intravenous isoproterenol was used (maximum dose, 6 µg/min) when needed. Activation mapping of VT was always performed when non-contact array was used (before 2012), especially in patients with haemodynamically unstable VT. In patients with haemodynamically tolerated and sustained VT, both activation and entrainment mapping would be performed. Pace mapping was performed if the VT is unstable or not inducible but recorded by a 12-lead electrocardiogram, and the ablation would be guided on the basis of detailed characterization of the substrate mapping (split or delayed potentials, discrete higher-voltage channels in the low-voltage region).17 An endocardial approach was used initially, with epicardial ablation procedures reserved for those patients who failed an endocardial ablation. Epicardial access was obtained from subxiphoid area under the guide of X-ray since 2014.18 An 8.5-Fr steerable sheath (Agilis, St Jude Medical, St Paul, MN, USA) was introduced to the epicardium. Deca-polar steerable catheter or ablation catheter was used to conduct activation or substrate mapping. Among the 284 patients in this series, 271 patients underwent only an endocardial approach, 8 patients underwent an endocardial and epicardial approach at the same session, and 5 patients underwent an initial endocardial approach with a separate epicardial VT ablation performed one or more weeks later. Regional ablation strategy was applied in all cases by using irrigated catheter at the target sites based on mapping findings with the upper power limits of 30–40 W and temperature limit of 45°C.7 Acute success is defined as no inducibility of any sustained ventricular arrhythmias at two different points despite a complete stimulation protocol for at least three times. Induced VT with similar morphology but a slower rate (with cycle length 30% longer and ≤160 b.p.m.) was defined as partial success. Substrate modification is defined as, in case of non-induction and unmappable VT, the abolishment of all delayed and/or fractioned potentials. Follow-up Patients’ follow-up was carried out every 6 months after discharge via telephone or outpatient visit. For the 41 patients with an ICD, ICD interrogations were conducted every 3–6 months in the device clinic. The primary endpoint of this study was freedom from death or cardiac transplantation. Another endpoint was the recurrence of sustained VT and/or appropriate ICD therapy. Follow-up data after the last procedure were reported for whom underwent multiple procedures. Statistical analyses Statistical analyses were performed using SPSS 20.0 software (SPSS Inc., Chicago, IL, USA). Continuous variables were presented as mean ± standard deviation or median (range). Categorical variables were presented as frequencies and percentages. The Mann–Whitney U and Kruskal–Wallis H tests were used to compare continuous variables between groups if the variable was not normally distributed. The χ2 analysis was used to compare the categorical variables between groups. Cox regression analyses were performed to evaluate predictors associated with the long-term endpoint outcomes. The following variables including age, gender and parameters of 2D ultrasound, and diagnostic category were analysed. All tests were two-tailed and a statistical significance was established at a P < 0.05. Results Study population There were 284 consecutive patients (231 male) with average age 38.2 ± 13.3 (14–76) years enrolled. The clinical characteristics are listed in Table 1. The age of symptom onset was 34.1 ± 13.2 years. More than half of the patients [155 (54.6%)] presented before 35 years’ old. The most common symptom was palpitation which was complained by 169 (59.5%) patients. Before the primary ablation, there were 155 (54.6%) patients who presented with a history of syncope and 92 (32.4%) patients had a cardiac arrest and cardiopulmonary resuscitation. Left ventricular ejection fraction <50% detected using transthoracic echocardiography and magnetic resonance imaging was observed in 28 patients. The rate of clinical VT reached 188.8 ± 42.3 b.p.m. Genetic data were available for 119 patients of whom 86 patients showed pathogenic desmosomal mutations. Table 1 Baseline characteristics of the study cohort (n = 284) Age (years), mean ± SD 38.2 ± 13.3 Male, n (%) 231 (81.3) Syncope, n (%) 159 (53) BMI (kg/m2), mean ± SD 23.8 ± 3.5 Rate of clinical VT (b.p.m.), mean ± SD 188.8 ± 42.3 Initial symptoms, n (%)  Palpitation 169 (59.2)  Syncope 155 (54.6)  Presyncope 28 (10.0) TTE  RV dilation, n (%) 98 (34.5)  LV dimension (mm), mean ± SD 47.5 ± 5.6  LVEF (%), mean ± SD 60.8 ± 8.7 Comorbidity, n (%)  Diabetes mellitus 10 (3.5)  Hypertension 30 (10.6)  Hyperlipidaemia 17 (6.0) NYHA, n (%)  I 247 (87.0)  II 33 (11.6)  III 1 (0.3)  IV 0 (0.0) Pathogenic mutation, n (%)  PKP2 53 (18.7)  DSG-2 21 (7.4)  DSC-2 6 (2.1)  DSP 6 (2.1) Global or regional dysfunction and structural alterations, n (%)  Major 101 (35.6)  Minor 35 (12.3) Tissue characterization of wall, n (%)  Major 5 (1.8)  Minor 0 (0.0) Repolarization abnormalities, n (%)  Major 124 (43.7)  Minor 34 (12.0) Depolarization/conduction abnormalities, n (%)  Major 36 (12.7)  Minor 47 (16.5) Arrhythmias, n (%)  Major 259 (92.0)  Minor 25 (8.8) Family history, n (%)  Major 56 (19.7)  Minor 4 (1.4) Medicines at discharge, n (%)  β-Blocker 55 (19.4)  Mexiletine 9 (3.2)  Propafenone 20 (7.0)  Sotalol 163 (57.4)  Amiodarone 22 (7.7) Age (years), mean ± SD 38.2 ± 13.3 Male, n (%) 231 (81.3) Syncope, n (%) 159 (53) BMI (kg/m2), mean ± SD 23.8 ± 3.5 Rate of clinical VT (b.p.m.), mean ± SD 188.8 ± 42.3 Initial symptoms, n (%)  Palpitation 169 (59.2)  Syncope 155 (54.6)  Presyncope 28 (10.0) TTE  RV dilation, n (%) 98 (34.5)  LV dimension (mm), mean ± SD 47.5 ± 5.6  LVEF (%), mean ± SD 60.8 ± 8.7 Comorbidity, n (%)  Diabetes mellitus 10 (3.5)  Hypertension 30 (10.6)  Hyperlipidaemia 17 (6.0) NYHA, n (%)  I 247 (87.0)  II 33 (11.6)  III 1 (0.3)  IV 0 (0.0) Pathogenic mutation, n (%)  PKP2 53 (18.7)  DSG-2 21 (7.4)  DSC-2 6 (2.1)  DSP 6 (2.1) Global or regional dysfunction and structural alterations, n (%)  Major 101 (35.6)  Minor 35 (12.3) Tissue characterization of wall, n (%)  Major 5 (1.8)  Minor 0 (0.0) Repolarization abnormalities, n (%)  Major 124 (43.7)  Minor 34 (12.0) Depolarization/conduction abnormalities, n (%)  Major 36 (12.7)  Minor 47 (16.5) Arrhythmias, n (%)  Major 259 (92.0)  Minor 25 (8.8) Family history, n (%)  Major 56 (19.7)  Minor 4 (1.4) Medicines at discharge, n (%)  β-Blocker 55 (19.4)  Mexiletine 9 (3.2)  Propafenone 20 (7.0)  Sotalol 163 (57.4)  Amiodarone 22 (7.7) Genetic data were available for 119 patients. BMI, body mass index; DSC-2, desmocollin-2; DSG-2, desmoglein-2; DSP, desmoplakin; LV dimension, left ventricular dimension; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; PKP2, plakophilin-2 gene; RV dilation, right ventricular dilation; SD, standard deviation; TTE, transthoracic echocardiography; VT, ventricular tachycardia. Open in new tab Table 1 Baseline characteristics of the study cohort (n = 284) Age (years), mean ± SD 38.2 ± 13.3 Male, n (%) 231 (81.3) Syncope, n (%) 159 (53) BMI (kg/m2), mean ± SD 23.8 ± 3.5 Rate of clinical VT (b.p.m.), mean ± SD 188.8 ± 42.3 Initial symptoms, n (%)  Palpitation 169 (59.2)  Syncope 155 (54.6)  Presyncope 28 (10.0) TTE  RV dilation, n (%) 98 (34.5)  LV dimension (mm), mean ± SD 47.5 ± 5.6  LVEF (%), mean ± SD 60.8 ± 8.7 Comorbidity, n (%)  Diabetes mellitus 10 (3.5)  Hypertension 30 (10.6)  Hyperlipidaemia 17 (6.0) NYHA, n (%)  I 247 (87.0)  II 33 (11.6)  III 1 (0.3)  IV 0 (0.0) Pathogenic mutation, n (%)  PKP2 53 (18.7)  DSG-2 21 (7.4)  DSC-2 6 (2.1)  DSP 6 (2.1) Global or regional dysfunction and structural alterations, n (%)  Major 101 (35.6)  Minor 35 (12.3) Tissue characterization of wall, n (%)  Major 5 (1.8)  Minor 0 (0.0) Repolarization abnormalities, n (%)  Major 124 (43.7)  Minor 34 (12.0) Depolarization/conduction abnormalities, n (%)  Major 36 (12.7)  Minor 47 (16.5) Arrhythmias, n (%)  Major 259 (92.0)  Minor 25 (8.8) Family history, n (%)  Major 56 (19.7)  Minor 4 (1.4) Medicines at discharge, n (%)  β-Blocker 55 (19.4)  Mexiletine 9 (3.2)  Propafenone 20 (7.0)  Sotalol 163 (57.4)  Amiodarone 22 (7.7) Age (years), mean ± SD 38.2 ± 13.3 Male, n (%) 231 (81.3) Syncope, n (%) 159 (53) BMI (kg/m2), mean ± SD 23.8 ± 3.5 Rate of clinical VT (b.p.m.), mean ± SD 188.8 ± 42.3 Initial symptoms, n (%)  Palpitation 169 (59.2)  Syncope 155 (54.6)  Presyncope 28 (10.0) TTE  RV dilation, n (%) 98 (34.5)  LV dimension (mm), mean ± SD 47.5 ± 5.6  LVEF (%), mean ± SD 60.8 ± 8.7 Comorbidity, n (%)  Diabetes mellitus 10 (3.5)  Hypertension 30 (10.6)  Hyperlipidaemia 17 (6.0) NYHA, n (%)  I 247 (87.0)  II 33 (11.6)  III 1 (0.3)  IV 0 (0.0) Pathogenic mutation, n (%)  PKP2 53 (18.7)  DSG-2 21 (7.4)  DSC-2 6 (2.1)  DSP 6 (2.1) Global or regional dysfunction and structural alterations, n (%)  Major 101 (35.6)  Minor 35 (12.3) Tissue characterization of wall, n (%)  Major 5 (1.8)  Minor 0 (0.0) Repolarization abnormalities, n (%)  Major 124 (43.7)  Minor 34 (12.0) Depolarization/conduction abnormalities, n (%)  Major 36 (12.7)  Minor 47 (16.5) Arrhythmias, n (%)  Major 259 (92.0)  Minor 25 (8.8) Family history, n (%)  Major 56 (19.7)  Minor 4 (1.4) Medicines at discharge, n (%)  β-Blocker 55 (19.4)  Mexiletine 9 (3.2)  Propafenone 20 (7.0)  Sotalol 163 (57.4)  Amiodarone 22 (7.7) Genetic data were available for 119 patients. BMI, body mass index; DSC-2, desmocollin-2; DSG-2, desmoglein-2; DSP, desmoplakin; LV dimension, left ventricular dimension; LVEF, left ventricular ejection fraction; NYHA, New York Heart Association; PKP2, plakophilin-2 gene; RV dilation, right ventricular dilation; SD, standard deviation; TTE, transthoracic echocardiography; VT, ventricular tachycardia. Open in new tab Implantable cardioverter-defibrillator was implanted in 41 (14.4%) patients, 12 (29.3%) of whom after the first ablation procedure. The indication for ICD implantation was documented sustained VT in 17 patients and sudden cardiac death in 24 patients. Patients refused ICD implantation mainly due to economic considerations and but also due to fear of inappropriate ICD discharge. A total of 67 prior catheter ablation procedures were performed in 63 patients before being referred to our centre. Electrophysiology and catheter ablation Totally, 393 catheter ablation procedures (endocardium only = 377, endo-epicardium = 16) were conducted, of which, 158 patients underwent a single procedure with the rest of 2.5 ± 0.7 procedures. Characteristics of the electrophysiological study were shown in Table 2. Ventricular tachycardia was induced in 310 (78.9%) with median 2 VTs [range (1–11)] per procedure. Non-mappable VT occurred in 67 (16.4%) procedures (non-sustained VT = 15, syncope = 52). The rate of mappable VT reached 209.4 ± 38.0 b.p.m. Ventricular fibrillation was induced or deteriorated from VT in 13 (3.2%) procedures. Left bundle branch block with superior axis was the most common types [induced in 291procedures (74.0%); median type: 1 (0–7); average rate: 207.6 ± 39.9 b.p.m.]. Table 2 Electrophysiological findings in the procedures (n = 393) VTs in the procedure  0 82  1 123  2 82  3 53  4 22  5 14  ≥6 16 Syncope, n (%) 55 (14.0) Mappable VT  LBBB with superior axis, n (%) 293 (74.5%)   Types, median (range) 1 (1–7)   Rate (b.p.m.), mean ± SD 207.6 ± 40.0  LBBB with inferior axis, n (%) 59 (15.0)   Types, median (range) 1 (1–3)   Rate (b.p.m.), mean ± SD 209.8 ± 67.5  RBBB with superior axis, n (%) 26 (6.6%)   Types, median (range) 1 (1–3)   Rate (b.p.m.), mean ± SD 210.5 ± 60.2  RBBB with inferior axis, n (%) 6 (1.5%)   Types 1   Rate (b.p.m.), mean ± SD 225.8 ± 60.0 VTs in the procedure  0 82  1 123  2 82  3 53  4 22  5 14  ≥6 16 Syncope, n (%) 55 (14.0) Mappable VT  LBBB with superior axis, n (%) 293 (74.5%)   Types, median (range) 1 (1–7)   Rate (b.p.m.), mean ± SD 207.6 ± 40.0  LBBB with inferior axis, n (%) 59 (15.0)   Types, median (range) 1 (1–3)   Rate (b.p.m.), mean ± SD 209.8 ± 67.5  RBBB with superior axis, n (%) 26 (6.6%)   Types, median (range) 1 (1–3)   Rate (b.p.m.), mean ± SD 210.5 ± 60.2  RBBB with inferior axis, n (%) 6 (1.5%)   Types 1   Rate (b.p.m.), mean ± SD 225.8 ± 60.0 LBBB, left bundle branch block; RBBB, right bundle branch block; SD, standard deviation; VTs, ventricular tachycardias. Open in new tab Table 2 Electrophysiological findings in the procedures (n = 393) VTs in the procedure  0 82  1 123  2 82  3 53  4 22  5 14  ≥6 16 Syncope, n (%) 55 (14.0) Mappable VT  LBBB with superior axis, n (%) 293 (74.5%)   Types, median (range) 1 (1–7)   Rate (b.p.m.), mean ± SD 207.6 ± 40.0  LBBB with inferior axis, n (%) 59 (15.0)   Types, median (range) 1 (1–3)   Rate (b.p.m.), mean ± SD 209.8 ± 67.5  RBBB with superior axis, n (%) 26 (6.6%)   Types, median (range) 1 (1–3)   Rate (b.p.m.), mean ± SD 210.5 ± 60.2  RBBB with inferior axis, n (%) 6 (1.5%)   Types 1   Rate (b.p.m.), mean ± SD 225.8 ± 60.0 VTs in the procedure  0 82  1 123  2 82  3 53  4 22  5 14  ≥6 16 Syncope, n (%) 55 (14.0) Mappable VT  LBBB with superior axis, n (%) 293 (74.5%)   Types, median (range) 1 (1–7)   Rate (b.p.m.), mean ± SD 207.6 ± 40.0  LBBB with inferior axis, n (%) 59 (15.0)   Types, median (range) 1 (1–3)   Rate (b.p.m.), mean ± SD 209.8 ± 67.5  RBBB with superior axis, n (%) 26 (6.6%)   Types, median (range) 1 (1–3)   Rate (b.p.m.), mean ± SD 210.5 ± 60.2  RBBB with inferior axis, n (%) 6 (1.5%)   Types 1   Rate (b.p.m.), mean ± SD 225.8 ± 60.0 LBBB, left bundle branch block; RBBB, right bundle branch block; SD, standard deviation; VTs, ventricular tachycardias. Open in new tab Table 3 Related factors of VT recurrence . Univariate analysis . P-value . Multivariate analysis . P-value . HR (95% CI) . HR (95% CI) . Gender 0.699 (0.454–1.078) 0.105 0.685 (0.444–1.057) 0.088 Age 0.994 (0.983–1.006) 0.327 0.994 (0.982–1.005) 0.295 With activation mapping 1.290 (0.855–1.947) 0.225 1.120 (0.724–2.046) 0.611 VTs (≥3) 1.482 (1.083–2.027) 0.007 1.467 (1.052–2.046) 0.024 . Univariate analysis . P-value . Multivariate analysis . P-value . HR (95% CI) . HR (95% CI) . Gender 0.699 (0.454–1.078) 0.105 0.685 (0.444–1.057) 0.088 Age 0.994 (0.983–1.006) 0.327 0.994 (0.982–1.005) 0.295 With activation mapping 1.290 (0.855–1.947) 0.225 1.120 (0.724–2.046) 0.611 VTs (≥3) 1.482 (1.083–2.027) 0.007 1.467 (1.052–2.046) 0.024 CI, confidence interval; HR, hazard ratio; VTs, ventricular tachycardias. Open in new tab Table 3 Related factors of VT recurrence . Univariate analysis . P-value . Multivariate analysis . P-value . HR (95% CI) . HR (95% CI) . Gender 0.699 (0.454–1.078) 0.105 0.685 (0.444–1.057) 0.088 Age 0.994 (0.983–1.006) 0.327 0.994 (0.982–1.005) 0.295 With activation mapping 1.290 (0.855–1.947) 0.225 1.120 (0.724–2.046) 0.611 VTs (≥3) 1.482 (1.083–2.027) 0.007 1.467 (1.052–2.046) 0.024 . Univariate analysis . P-value . Multivariate analysis . P-value . HR (95% CI) . HR (95% CI) . Gender 0.699 (0.454–1.078) 0.105 0.685 (0.444–1.057) 0.088 Age 0.994 (0.983–1.006) 0.327 0.994 (0.982–1.005) 0.295 With activation mapping 1.290 (0.855–1.947) 0.225 1.120 (0.724–2.046) 0.611 VTs (≥3) 1.482 (1.083–2.027) 0.007 1.467 (1.052–2.046) 0.024 CI, confidence interval; HR, hazard ratio; VTs, ventricular tachycardias. Open in new tab The results of substrate mapping and critical VT targets were shown in Figure 1. Right ventricular sub-tricuspid valvular regions accounted for the majority of low-voltage area, abnormal potentials and VT critical sites. Low-voltage area located mostly at the RV basal free wall (73.9%) with RV basal inferior wall, mid-lateral wall accounting for 31.4% and 32.2%, respectively. Same distributed pattern was observed in abnormal potentials. Right ventricular basal-mid lateral wall was the most commonly area detected abnormal potentials (65.5%). Right ventricular basal inferior wall, RV outflow tract (RVOT), and RV apex accounts for 33.3%, 31.3%, and 10.2%. Figure 1 Open in new tabDownload slide Distribution of substrate mapping results and critical sites of VTs. (A) Low-voltage area distribution; (B) abnormal potentials distribution; and (C) VT critical sites distribution. RV, right ventricular; RVOT, right ventricular outflow tract; VT, ventricular tachycardia. Figure 1 Open in new tabDownload slide Distribution of substrate mapping results and critical sites of VTs. (A) Low-voltage area distribution; (B) abnormal potentials distribution; and (C) VT critical sites distribution. RV, right ventricular; RVOT, right ventricular outflow tract; VT, ventricular tachycardia. Epicardial mapping was recommended when endocardial ablation failed. Four patients refused the epicardial approach due to fear of severe complications. Furthermore, two epicardial punctures failed to due to abnormal anatomy and adhesions. Five procedures showed VT targets from endocardium rather than appositional epicardial sites probably due to large dense scar of epicardium (one typical example was shown in Supplementary material online, Figure S1). Repeated electrophysiological examination was performed at the end of ablation. Acute success was reached in 276 (70.2%) procedures a partial success in 36 (9.2%). Follow-up outcomes and related risk factors Ventricular tachycardia recurrence After 46.3 ± 40.7 months’ (median 36.0) follow-up, 123 patients underwent 171 recurrences. Ventricular tachycardia-free survival rate after first, second, and last ablation procedure was 56.7%, 73.2%, and 78.1%. The survival curve free from sustained VT recurrence and/or appropriate ICD therapy was shown in Figure 2A. Univariate analysis showed induced VTs ≥3 types in the procedure correlated with VT recurrence which was adjusted by multivariate analysis [hazard ratio (HR) 1.467, 95% confidence interval (CI) 1.052–2.046; P = 0.024] (Table 3, Figure 2B). Notably, mapping strategies (with activation mapping vs. without activation mapping) were not associated with VT recurrence (HR 1.120, 95% CI 0.724–2.046; P = 0.611). Figure 2 Open in new tabDownload slide Survival curve free from VT recurrence and related factor. (A) Survival curve free from VT recurrence and (B) impact of induced VTs in the procedure. VT, ventricular tachycardia. Figure 2 Open in new tabDownload slide Survival curve free from VT recurrence and related factor. (A) Survival curve free from VT recurrence and (B) impact of induced VTs in the procedure. VT, ventricular tachycardia. Table 4 Related factors with all-cause mortality . Univariate analysis . P-value . Multivariate analysis . P-value . HR (95% CI) . HR (95% CI) . Age 0.993 (0.960–1.026) 0.673 0.984 (0.947–1.021) 0.393 Gender 1.343 (0.492–3.668) 0.565 2.338 (0.743–7.356) 0.147 LVEF<50% 3.114 (1.010–9.596) 0.048 2.473 (0.762–8.027) 0.132 Syncope during the procedure 2.793 (1.157–6.740) 0.022 1.026 (0.311–3.380) 0.967 VT recurrence 6.195 (2.566–14.956) <0.001 2.954 (1.086–8.038) 0.034 VT induced in the procedure 5.145 (2.166–12.222) <0.001 3.189 (1.073–9.482) 0.037 . Univariate analysis . P-value . Multivariate analysis . P-value . HR (95% CI) . HR (95% CI) . Age 0.993 (0.960–1.026) 0.673 0.984 (0.947–1.021) 0.393 Gender 1.343 (0.492–3.668) 0.565 2.338 (0.743–7.356) 0.147 LVEF<50% 3.114 (1.010–9.596) 0.048 2.473 (0.762–8.027) 0.132 Syncope during the procedure 2.793 (1.157–6.740) 0.022 1.026 (0.311–3.380) 0.967 VT recurrence 6.195 (2.566–14.956) <0.001 2.954 (1.086–8.038) 0.034 VT induced in the procedure 5.145 (2.166–12.222) <0.001 3.189 (1.073–9.482) 0.037 CI, confidence interval; HR, hazard ratio; LVEF, left ventricular ejection fraction; VTs, ventricular tachycardias. Open in new tab Table 4 Related factors with all-cause mortality . Univariate analysis . P-value . Multivariate analysis . P-value . HR (95% CI) . HR (95% CI) . Age 0.993 (0.960–1.026) 0.673 0.984 (0.947–1.021) 0.393 Gender 1.343 (0.492–3.668) 0.565 2.338 (0.743–7.356) 0.147 LVEF<50% 3.114 (1.010–9.596) 0.048 2.473 (0.762–8.027) 0.132 Syncope during the procedure 2.793 (1.157–6.740) 0.022 1.026 (0.311–3.380) 0.967 VT recurrence 6.195 (2.566–14.956) <0.001 2.954 (1.086–8.038) 0.034 VT induced in the procedure 5.145 (2.166–12.222) <0.001 3.189 (1.073–9.482) 0.037 . Univariate analysis . P-value . Multivariate analysis . P-value . HR (95% CI) . HR (95% CI) . Age 0.993 (0.960–1.026) 0.673 0.984 (0.947–1.021) 0.393 Gender 1.343 (0.492–3.668) 0.565 2.338 (0.743–7.356) 0.147 LVEF<50% 3.114 (1.010–9.596) 0.048 2.473 (0.762–8.027) 0.132 Syncope during the procedure 2.793 (1.157–6.740) 0.022 1.026 (0.311–3.380) 0.967 VT recurrence 6.195 (2.566–14.956) <0.001 2.954 (1.086–8.038) 0.034 VT induced in the procedure 5.145 (2.166–12.222) <0.001 3.189 (1.073–9.482) 0.037 CI, confidence interval; HR, hazard ratio; LVEF, left ventricular ejection fraction; VTs, ventricular tachycardias. Open in new tab Recurrences decreased significantly year by year (Figure 3). The median time from ablation to recurrence is 17.3 months (range 0–157.0). Totally, 99 (57.9%) recurrences occurred within 2 years. Compared with patients in whom VT recurred within 2 years, those beyond were more likely to demonstrate new VT targets (10.1% vs. 1.4%, P = 0.022) (Supplementary material online, Figure S2). The number of induced VTs in the procedure, age, gender, and the use of activation or substrate mapping were not significantly different between patients recurred within or beyond 2 years. Figure 3 Open in new tabDownload slide Patients underwent VT recurrence negatively correlated with follow-up time (r = −0.795, P = 0.006). VT, ventricular tachycardia. Figure 3 Open in new tabDownload slide Patients underwent VT recurrence negatively correlated with follow-up time (r = −0.795, P = 0.006). VT, ventricular tachycardia. Redo ablation procedures There were 109 redo ablation procedures in 81 patients (second time = 81 and equal to or more than 3 times = 28). New targets were observed in 68.8% procedures, which may be explained by the disease progression or incomplete ablation. Incidence of preprocedural syncope decrease significantly for first, second, and more than 3 times ablation procedure [155 (54.6%) vs. 13 (16.5%) vs.1 (3.6%), P < 0.001]. Ventricular tachycardia induction rate, types of VT, fastest rate of VT in the procedure, and time interval between subsequent procedures were not significantly different in the three groups (P > 0.05). All-cause mortality During follow-up time of 73.0 ± 50.1 months (median 64), 19 patients died (12 patients died of sudden cardiac death). Multivariate analysis showed VT recurrence and induced VTs ≥3 types in the procedure were associated with death (HR 2.954, 95% CI 1.806–8.038; P = 0.034; HR 3.189, 95% CI 1.073–9.482; P = 0.037) which were also significant after adjusted by age and gender (Table 4, Figure 4). Figure 4 Open in new tabDownload slide Survival curve free from death. (A) Survival curve free from death; (B) impact of VT recurrence on all-cause mortality; and (C) impact of induced VTs in the procedure on all-cause mortality. VT, ventricular tachycardia. Figure 4 Open in new tabDownload slide Survival curve free from death. (A) Survival curve free from death; (B) impact of VT recurrence on all-cause mortality; and (C) impact of induced VTs in the procedure on all-cause mortality. VT, ventricular tachycardia. Complications Right ventricular perforation was observed in one patient whose RV apex showed aneurysm in transthoracic echocardiography. The patient was stable after drainage and suffered from sudden cardiac death 1 month after discharge. There were no procedure-related deaths. Discussion Main findings This is a large cohort study aimed at evaluating the long-term prognosis of patients of VT with ARVC underwent catheter ablation. Recurrences decreased significantly according to year. Repeated endocardial ablation (combined with epicardial when necessary) was considered effective and efficacy in facilitating VT control and the reduction in the rate of recurrent syncope. Induced VTs (≥3 types) in the procedure is the major risk factor independently associated with worse outcomes. New targets were found in most of the redo procedures. Arrhythmogenic right ventricular cardiomyopathy is associated with an increased risk of sudden death.7,11 In our cohort, syncope occurred in half of the patients and two-thirds underwent cardiopulmonary resuscitation outside hospital. These patients were in intermediate- or high-risk state.8 Implantable cardioverter-defibrillator implantation is generally recommended in patients who have experienced sustained VT, cardiac syncope, and/or sudden death.3 However, due to the finical reason and the fear of inappropriate discharges, only a small number of patients received ICD implantation.7 In this study, only less than one-sixth of patients received ICD implantation. Catheter ablation was considered as an effective method to terminate VT and reduce VT burden with the successful rate more than 80% with repeated procedures.4,5,7 However, long-term (10 years) follow-up data showed VT-free survival rate dropped to 14–15%. In our study, although incidence of VT recurrence also remains high during follow-up period, redo endocardial ablation procedures may help to remain VT suppression. Studies demonstrated that disease progression or the progressively pathological replacement of myocytes considered as one of the characteristics of ARVC which may cause VT recurrence.4 Similar to the prior studies, new critical VT targets were observed in most redo procedures. Furthermore, this study found that those recurrent beyond 2 years were more likely to demonstrate new VT targets. The median number of VTs induced during the baseline electrophysiology study was 2. Unmappable VTs (non-sustained VT, haemodynamical unstable, and deteriorating to ventricular fibrillation) occurred in one-third of the procedures. For patients with unmappable VT, substrate mapping was proved to be an effective method.19 In this study, multivariate analysis showed mapping strategy (with or without activation) was not associated with VT recurrence. In addition, for the mappable VTs, the most common targets were sub-tricuspid valvular regions, followed by RVOT and RV apical region. The same distributed pattern was also observed in the substrate mapping results, which demonstrates substrate mapping may be considered as an important alternative method. Furthermore, this study demonstrates that VTs induced in the procedure was correlated with worse outcomes. For these patients, ICD implantation was strongly recommended. Epicardial ablation has been reported to result in higher VT-free survival rates than endocardial ablation.12 The mapping results showed low bipolar voltage area is more widely spread in the epicardium than that of endocardium especially for patients with minimal RV structural changes and for those with limited endocardial abnormal substrate and/or failed prior endocardial ablation.5 However, large dense scar of epicardium without satisfied potential, in which cases VT terminated in the endocardium, also happened. What’s more, complications regarding the epicardial procedure were very high. Although complications of epicardial puncture (RV puncture) might be mitigated using coronary vein exit and carbon dioxide insufflation,20 coronary artery injury, pericardial inflammatory reaction, and other complications cannot be avoided. In our study, some of the patients even refused to choose epicardial puncture for fear of the related complications. On the other hand, it is also happened that failure to find satisfying targets from epicardium due to large low-voltage area and dense scar. Studies have demonstrated endocardial procedures may reflect and eliminate epicardial local abnormal ventricular activity.13 Data from our study demonstrate that endocardial ablation and appropriate epicardial ablation demonstrates favourable results. In our centre, ablation was performed via epicardial access only when endocardial ablation failed or no abnormal pace or substrate mapping targets was found intracardially. Ventricular tachycardias ≥3 strongly indicates worse follow-up outcome irrespective of ablation access and acute procedure endpoints. Careful endocardial mapping should be a prior consideration with epicardial access chosen as an alternative method. Study limitations There exist limitations. Firstly, time span of 18 years indicates the strategy of mapping and ablation evolved significantly which may have an influence on the interpretation of the results. What’s more, related factors combining clinical data were included to analyse rather than genetic testing which might provide more information on the results of catheter ablation. Thirdly, there were only 41 patients underwent ICD implantation which may underestimate the recurrence rate of VT. Conclusions In conclusion, in this large cohort study, most of the patients with ARVC and VT were in intermediate or high risk of sudden cardiac death state. The majority of the patients chose catheter ablation as the first choice. Endocardial and/or epicardial ablation achieved relatively high survival rate free from VT recurrence and death. Induced VTs ≥3 in one procedure was shown to be related risk factors with worse outcomes. Acknowledgements We are indebted to Professor Hugh Calkins who reviewed the manuscript. Funding This work was supported by the National Key R&D Program of China (2017YFC1307800), Beijing Municipal Science and Technology Commission (Z161100000516022), and National Natural Science Foundation (81570309). Conflict of interest: none declared. References 1 Corrado D , Fontaine G, Marcus FI, McKenna WJ, Nava A, Thiene G et al. Arrhythmogenic right ventricular dysplasia/cardiomyopathy: need for an international registry. Study Group on Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy of the Working Groups on Myocardial and Pericardial Disease and Arrhythmias of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the World Heart Federation . Circulation 2000 ; 101 : E101 – 6 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Cappelletto C , Stolfo D, De Luca A, Pinamonti B, Barbati G, Pivetta A et al. Lifelong arrhythmic risk stratification in arrhythmogenic right ventricular cardiomyopathy: distribution of events and impact of periodical reassessment . Europace 2018 ; 20 : f20 – 9 . Google Scholar Crossref Search ADS PubMed WorldCat 3 Corrado D , Wichter T, Link MS, Hauer R, Marchlinski F, Anastasakis A et al. Treatment of arrhythmogenic right ventricular cardiomyopathy/dysplasia: an international task force consensus statement . Eur Heart J 2015 ; 36 : 3227 – 37 . Google Scholar Crossref Search ADS PubMed WorldCat 4 Souissi Z , Boule S, Hermida JS, Doucy A, Mabo P, Pavin D et al. Catheter ablation reduces ventricular tachycardia burden in patients with arrhythmogenic right ventricular cardiomyopathy: insights from a North-Western French Multicentre Registry . Europace 2018 ; 20 : 362 – 9 . Google Scholar Crossref Search ADS PubMed WorldCat 5 Kirubakaran S , Bisceglia C, Silberbauer J, Oloriz T, Santagostino G, Yamase M et al. Characterization of the arrhythmogenic substrate in patients with arrhythmogenic right ventricular cardiomyopathy undergoing ventricular tachycardia ablation . Europace 2017 ; 19 : 1049 – 62 . Google Scholar Crossref Search ADS PubMed WorldCat 6 Fontaine G , Frank R, Rougier I, Tonet JL, Gallais Y, Fareno G et al. Electrode catheter ablation of resistant ventricular tachycardia in arrhythmogenic right ventricular dysplasia: experience of 13 patients with a mean follow-up of 45 months . Eur Heart J 1989 ; 10 : 74 – 81 . Google Scholar Crossref Search ADS PubMed WorldCat 7 Yao Y , Zhang S, He DS, Zhang K, Hua W, Chu J et al. Radiofrequency ablation of the ventricular tachycardia with arrhythmogenic right ventricular cardiomyopathy using non-contact mapping . Pacing Clin Electrophysiol 2007 ; 30 : 526 – 33 . Google Scholar Crossref Search ADS PubMed WorldCat 8 Calkins H , Corrado D, Marcus F. Risk stratification in arrhythmogenic right ventricular cardiomyopathy . Circulation 2017 ; 136 : 2068 – 82 . Google Scholar Crossref Search ADS PubMed WorldCat 9 Garcia FC , Bazan V, Zado ES, Ren JF, Marchlinski FE. Epicardial substrate and outcome with epicardial ablation of ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy/dysplasia . Circulation 2009 ; 120 : 366 – 75 . Google Scholar Crossref Search ADS PubMed WorldCat 10 Jais P , Maury P, Khairy P, Sacher F, Nault I, Komatsu Y et al. Elimination of local abnormal ventricular activities: a new end point for substrate modification in patients with scar-related ventricular tachycardia . Circulation 2012 ; 125 : 2184 – 96 . Google Scholar Crossref Search ADS PubMed WorldCat 11 Marchlinski FE , Zado E, Dixit S, Gerstenfeld E, Callans DJ, Hsia H et al. Electroanatomic substrate and outcome of catheter ablative therapy for ventricular tachycardia in setting of right ventricular cardiomyopathy . Circulation 2004 ; 110 : 2293 – 8 . Google Scholar Crossref Search ADS PubMed WorldCat 12 Berruezo A , Acosta J, Fernandez-Armenta J, Pedrote A, Barrera A, Arana-Rueda E et al. Safety, long-term outcomes and predictors of recurrence after first-line combined endoepicardial ventricular tachycardia substrate ablation in arrhythmogenic cardiomyopathy. Impact of arrhythmic substrate distribution pattern. A prospective multicentre study . Europace 2017 ; 19 : 607 – 16 . Google Scholar Crossref Search ADS PubMed WorldCat 13 Komatsu Y , Daly M, Sacher F, Cochet H, Denis A, Derval N et al. Endocardial ablation to eliminate epicardial arrhythmia substrate in scar-related ventricular tachycardia . J Am Coll Cardiol 2014 ; 63 : 1416 – 26 . Google Scholar Crossref Search ADS PubMed WorldCat 14 Marcus FI , McKenna WJ, Sherrill D, Basso C, Bauce B, Bluemke DA et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria . Eur Heart J 2010 ; 31 : 806 – 14 . Google Scholar Crossref Search ADS PubMed WorldCat 15 Bao J , Wang J, Yao Y, Wang Y, Fan X, Sun K et al. Correlation of ventricular arrhythmias with genotype in arrhythmogenic right ventricular cardiomyopathy . Circ Cardiovasc Genet 2013 ; 6 : 552 – 6 . Google Scholar Crossref Search ADS PubMed WorldCat 16 Wu LM , Bao JR, Yao Y, Hou BB, Zheng LH, Zhang S. Fast rate (≥250 beats/min) right ventricular burst stimulation is useful for ventricular tachycardia induction in arrhythmogenic right ventricular cardiomyopathy . J Geriatr Cardiol 2016 ; 13 : 70 – 4 . Google Scholar PubMed OpenURL Placeholder Text WorldCat 17 Komatsu Y , Daly M, Sacher F, Derval N, Pascale P, Roten L et al. Electrophysiologic characterization of local abnormal ventricular activities in postinfarction ventricular tachycardia with respect to their anatomic location . Heart Rhythm 2013 ; 10 : 1630 – 7 . Google Scholar Crossref Search ADS PubMed WorldCat 18 Sosa E , Scanavacca M, D'Avila A, Pilleggi E. A new technique to perform epicardial mapping in the electrophysiology laboratory . J Cardiovasc Electrophysiol 1996 ; 7 : 531 – 6 . Google Scholar Crossref Search ADS PubMed WorldCat 19 Corrado D , Basso C, Leoni L, Tokajuk B, Turrini P, Bauce B et al. Three-dimensional electroanatomical voltage mapping and histologic evaluation of myocardial substrate in right ventricular outflow tract tachycardia . J Am Coll Cardiol 2008 ; 51 : 731 – 9 . Google Scholar Crossref Search ADS PubMed WorldCat 20 Silberbauer J , Gomes J, O’Nunain S, Kirubakaran S, Hildick-Smith D, McCready J. Coronary vein exit and carbon dioxide insufflation to facilitate subxiphoid epicardial access for ventricular mapping and ablation: first experience . JACC Clin Electrophysiol 2017 ; 3 : 514 – 21 . Google Scholar Crossref Search ADS PubMed WorldCat Author notes " Erpeng Liang, LingminWu and Siyang Fan contributed equally to this work. Published on behalf of the European Society of Cardiology. 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Europace – Oxford University Press

Published: May 1, 2020

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