Endocardial-Epicardial Catheter Ablation Versus Endocardial Catheter Ablation Alone for Ventricular Arrhythmia in Patients With Structural Heart Disease (Meta-Analysis of Reconstructed Time-to-Event Data)

Endocardial-epicardial (Endo-epi) catheter ablation (CA) has been shown to reduce the rate of ventricular arrhythmia (VA) ablation in patients with structural heart disease (SHD). However, the effectiveness of this technique compared with endocardial (Endo) CA alone remains uncertain. This meta-analysis aims to compare the effectiveness of Endo-epi versus Endo alone in reducing the risk of VA recurrence in patients with SHD. We searched PubMed, Embase, and Cochrane Central Register with a comprehensive strategy. We used reconstructed time-to-event data to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for VA recurrence accompanied by at least one Kaplan–Meier curve for ventricular tachycardia recurrence. Our meta-analysis included 11 studies with a total of 977 patients. Endo-epi had a significantly lower risk of VA recurrence compared with those treated with Endo alone (HR 0.43, 95% CI 0.32 to 0.57, p <0.001). Subgroup analysis based on the type of cardiomyopathy revealed that patients with arrhythmogenic right ventricular cardiomyopathy and ischemic cardiomyopathy (ICM) benefited significantly from Endo-epi in reducing the risk of VA recurrence (HR 0.835, 0.55 to 0.87, p <0.021). However, there was no significant difference with non-ICM (HR 0.440, 0.55 to 0.87, p <0.33). The analysis of conditional survival showed that patients who remained free of VA recurrence for 5 years after the procedure had a very low probability of developing VA recurrence thereafter. In conclusion, Endo-epi CA is more effective than Endo CA alone in reducing the risk of VA recurrence in patients with SHD, especially those with arrhythmogenic right ventricular cardiomyopathy and ICM. Endocardial-epicardial (Endo-epi) catheter ablation (CA) has been shown to reduce the rate of ventricular arrhythmia (VA) ablation in patients with structural heart disease (SHD). However, the effectiveness of this technique compared with endocardial (Endo) CA alone remains uncertain. This meta-analysis aims to compare the effectiveness of Endo-epi versus Endo alone in reducing the risk of VA recurrence in patients with SHD. We searched PubMed, Embase, and Cochrane Central Register with a comprehensive strategy. We used reconstructed time-to-event data to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for VA recurrence accompanied by at least one Kaplan–Meier curve for ventricular tachycardia recurrence. Our meta-analysis included 11 studies with a total of 977 patients. Endo-epi had a significantly lower risk of VA recurrence compared with those treated with Endo alone (HR 0.43, 95% CI 0.32 to 0.57, p <0.001). Subgroup analysis based on the type of cardiomyopathy revealed that patients with arrhythmogenic right ventricular cardiomyopathy and ischemic cardiomyopathy (ICM) benefited significantly from Endo-epi in reducing the risk of VA recurrence (HR 0.835, 0.55 to 0.87, p <0.021). However, there was no significant difference with non-ICM (HR 0.440, 0.55 to 0.87, p <0.33). The analysis of conditional survival showed that patients who remained free of VA recurrence for 5 years after the procedure had a very low probability of developing VA recurrence thereafter. In conclusion, Endo-epi CA is more effective than Endo CA alone in reducing the risk of VA recurrence in patients with SHD, especially those with arrhythmogenic right ventricular cardiomyopathy and ICM. In spite of the underlying arrhythmogenic substrate, ventricular tachycardia (VT) is a serious cause of morbidity and mortality.1Tung R Michowitz Y Yu R Mathuria N Vaseghi M Buch E Bradfield J Fujimura O Gima J Discepolo W Mandapati R Shivkumar K Epicardial ablation of ventricular tachycardia: an institutional experience of safety and efficacy.Heart Rhythm. 2013; 10: 490-498Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar The recurrence of defibrillator shocks because of VT is associated with poor quality of life and increased mortality.2Poole JE Johnson GW Hellkamp AS Anderson J Callans DJ Raitt MH Reddy RK Marchlinski FE Yee R Guarnieri T Talajic M Wilber DJ Fishbein DP Packer DL Mark DB Lee KL Bardy GH Prognostic importance of defibrillator shocks in patients with heart failure.N Engl J Med. 2008; 359: 1009-1017Crossref PubMed Scopus (1199) Google Scholar,3Moss AJ Zareba W Hall WJ Klein H Wilber DJ Cannom DS Daubert JP Higgins SL Brown MW Andrews ML Multicenter Automatic Defibrillator Implantation Trial II Investigators. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction.N Engl J Med. 2002; 346: 877-883Crossref PubMed Scopus (5764) Google Scholar Despite the potential benefits of antiarrhythmic drugs (AADs) to reduce ventricular arrhythmias (VAs), adjunct catheter ablation (CA) may be more effective.4Santangeli P Muser D Maeda S Filtz A Zado ES Frankel DS Dixit S Epstein AE Callans DJ Marchlinski FE. Comparative effectiveness of antiarrhythmic drugs and catheter ablation for the prevention of recurrent ventricular tachycardia in patients with implantable cardioverter-defibrillators: a systematic review and meta-analysis of randomized controlled trials.Heart Rhythm. 2016; 13: 1552-1559Abstract Full Text Full Text PDF PubMed Google Scholar CA is modestly effective for VT when epicardial mapping and ablation are performed, especially when the disease substrate is arrhythmogenic right ventricular cardiomyopathy (ARVC), nonischemic idiopathic dilated cardiomyopathy (NICM), Brugada phenotypes, and in some cases ischemic cardiomyopathy (ICM).5Bai R Di Biase L Shivkumar K Mohanty P Tung R Santangeli P Saenz LC Vacca M Verma A Khaykin Y Mohanty S Burkhardt JD Hongo R Beheiry S Dello Russo A Casella M Pelargonio G Santarelli P Sanchez J Tondo C Natale A Ablation of ventricular arrhythmias in arrhythmogenic right ventricular dysplasia/cardiomyopathy: arrhythmia-free survival after endo-epicardial substrate based mapping and ablation.Circ Arrhythm Electrophysiol. 2011; 4: 478-485Crossref PubMed Scopus (202) Google Scholar,6Philips B Madhavan S James C Tichnell C Murray B Dalal D Bhonsale A Nazarian S Judge DP Russell SD Abraham T Calkins H Tandri H. Outcomes of catheter ablation of ventricular tachycardia in arrhythmogenic right ventricular dysplasia/cardiomyopathy.Circ Arrhythm Electrophysiol. 2012; 5: 499-505Crossref PubMed Scopus (167) Google Scholar Endocardial-epicardial ablation (Endo-epi) for VT has been shown to result in better outcomes than endocardial ablation alone (Endo).5Bai R Di Biase L Shivkumar K Mohanty P Tung R Santangeli P Saenz LC Vacca M Verma A Khaykin Y Mohanty S Burkhardt JD Hongo R Beheiry S Dello Russo A Casella M Pelargonio G Santarelli P Sanchez J Tondo C Natale A Ablation of ventricular arrhythmias in arrhythmogenic right ventricular dysplasia/cardiomyopathy: arrhythmia-free survival after endo-epicardial substrate based mapping and ablation.Circ Arrhythm Electrophysiol. 2011; 4: 478-485Crossref PubMed Scopus (202) Google Scholar,7Izquierdo M Sánchez-Gómez JM Ferrero de Loma-Osorio A Martínez A Bellver A Peláez A Núñez J Núñez C Chorro J Ruiz-Granell R Endo-epicardial versus only-endocardial ablation as a first line strategy for the treatment of ventricular tachycardia in patients with ischemic heart disease.Circ Arrhythm Electrophysiol. 2015; 8: 882-889Crossref PubMed Scopus (44) Google Scholar The procedure, however, carries a risk of procedural complications, including inadvertent puncture of the right ventricle free wall with bleeding and injuries to the abdominal viscera, blood vessels, liver, or diaphragm.8Bradfield JS Tung R Boyle NG Buch E Shivkumar K. Our approach to minimize risk of epicardial access: standard techniques with the addition of electroanatomic mapping guidance.J Cardiovasc Electrophysiol. 2013; 24: 723-727Crossref PubMed Scopus (19) Google Scholar, 9Scanavacca MI Venancio AC Pisani CF Lara S Hachul D Darrieux F Hardy C Paola E Aiello VD Mahapatra S Sosa E Percutaneous transatrial access to the pericardial space for epicardial mapping and ablation.Circ Arrhythm Electrophysiol. 2011; 4: 331-336Crossref PubMed Scopus (21) Google Scholar, 10Aryana A Tung R d'Avila A. Percutaneous epicardial approach to catheter ablation of cardiac arrhythmias.JACC Clin Electrophysiol. 2020; 6: 1-20Crossref PubMed Scopus (13) Google Scholar A combined Endo-epi ablation has not been widely used as a standard treatment for VT because of these risks and an unproved benefit compared with an endocardial-only approach. As demonstrated in a previous meta-analysis by Romero et al11Romero J Patel K Briceno D Alviz I Gabr M Diaz JC Trivedi C Mohanty S Della Rocca D Al-Ahmad A Yang R Rios S Cerna L Du X Tarantino N Zhang XD Lakkireddy D Natale A Di Biase L Endo-epicardial ablation vs endocardial ablation for the management of ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy: a systematic review and meta-analysis.J Cardiovasc Electrophysiol. 2020; 31: 2022-2031Crossref PubMed Scopus (9) Google Scholar in a previous meta-analysis, Endo-epi VT ablation is associated with a significant reduction in VA recurrence when compared with Endo ablation alone but does not significantly affect all-cause mortality or acute procedural complications in patients with ARVC. Despite the high quality of the meta-analysis, authors used a fixed-effects model to pool their data for incident risk ratio (RR) measures despite a median average follow-up of just 4.4 years. In traditional meta-analyses, time-to-event outcomes are difficult to include. The researchers have used a pooled median survival rate, RR, or event rate derived from survival estimates at a given time point or they have directly derived RR. In all 3 approaches, Kaplan–Meier curves are not produced and censoring and proportional hazards assumptions are not recognized, which are central tenets of survival analysis.12Guyot P Ades AE Ouwens MJ Welton NJ. Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves.BMC Med Res Methodol. 2012; 12: 9Crossref PubMed Google Scholar Time-to-event meta-analysis has emerged as the gold standard in response to inconsistent reporting caused by divergent approaches, the “curve approach” has emerged as the gold standard.13Wei Y Royston P. Reconstructing time-to-event data from published Kaplan–Meier curves.STATA J. 2017; 17: 786-802Crossref PubMed Scopus (118) Google Scholar Reconstructing individual patient data (IPD) from published Kaplan–Meier graphs is achieved with this method. In this meta-analysis, using Kaplan–Meier-derived reconstructed IPD, we compared Endo-epi ablation for VT in patients with ARVC, NICM, and ICM versus Endo alone. In this review, we followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for systematic reviews.14Liberati A Altman DG Tetzlaff J Mulrow C Gøtzsche PC Ioannidis JP Clarke M Devereaux PJ Kleijnen J Moher D The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration.PLoS Med. 2009; 6e1000100Crossref Scopus (10668) Google Scholar We adhered to the statement of ethical publishing as appears in the American Journal of Cardiology (AJC). We included in this meta-analysis the nonrandomized controlled trials and cohort studies that included patients who had VT with ARVC, ICM, and NICM and underwent Endo-epi ablation and/or Endo CA therapy. We considered only the studies with VA recurrence outcomes with Kaplan–Meier curves. We excluded study designs without a control group, studies not reporting AV recurrence along Kaplan–Meier curves and studies restricted to patients with idiopathic ventricular arrhythmias without structural heart disease. We searched PubMed, Embase, and Cochrane Central Register for trials comparing Endo-epi ablation with Endo ablation alone to manage ARVC with VT. Literature searches were limited to studies published before August 2022 in these major databases. We used the following terms: ventricular tachycardia, ventricular arrhythmias, VT, or VA, with endocardial ablation, epicardial access, epicardial ablation, endo-epicardial ablation, radiofrequency ablation, CA, RFA and ARVD, ARVC, arrhythmogenic right ventricular dysplasia or ARVC. We systematically assessed the bias risk of included studies using the ROBINS-I (Risk of Bias in Non-Randomized Studies of Interventions tool).15Sterne JA Hernán MA Reeves BC Savović J Berkman ND Viswanathan M Henry D Altman DG Ansari MT Boutron I Carpenter JR Chan AW Churchill R Deeks JJ Hróbjartsson A Kirkham J Jüni P Loke YK Pigott TD Ramsay CR Regidor D Rothstein HR Sandhu L Santaguida PL Schünemann HJ Shea B Shrier I Tugwell P Turner L Valentine JC Waddington H Waters E Wells GA Whiting PF Higgins JP ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions.BMJ. 2016; 355: i4919Crossref PubMed Google Scholar There were 2 independent reviewers who assessed bias risk. In case of disagreement, a third reviewer evaluated the data and made the final decision. The summary risk of bias is demonstrated in Figure 1. The Reconstructed IPD: There are 2 steps to reconstructing IPD. The first step is data extraction from Kaplan–Meier curves. For this step, we used WebPlotDigitizer-4.5 to extract data coordinates time and survival probabilities. The second step is preprocessing the time and survival probabilities to get the reconstructed IPD (time, status). In this step, the iterative algorithm was introduced by Liu et al.16Liu N Zhou Y Lee JJ. IPDfromKM: reconstruct individual patient data from published Kaplan-Meier survival curves.BMC Med Res Methodol. 2021; 21: 111Crossref PubMed Scopus (87) Google Scholar To assess the accuracy of the reconstructed IPD data we considered: root mean square error ≤0.05, mean absolute error ≤0.02, and max absolute error ≤0.05. The Mann–Whitney test and Bootstrap t test were used to compare the distribution of the read-in and the new estimated survival curve, a large p value is desirable. Then, all data from the included studies were pooled for further analysis. Further, we compared the newly reconstructed IPD Kaplan–Meier curves with the original curves by inspection to make sure there is no difference between the reconstructed and original data. IPD from the KM package and R version 4.2.1 were used for this step. We used Kaplan–Meier to calculate the overall survival and log-rank test to compare the 2 groups with a p ≤0.05 to be considered statistically significant. Cox proportional hazards were used to build a regression model. Schoenfeld residuals test was used to test the proportional hazard assumption. The Cox regression model was validated for calibration accuracy in predicting the probability of surviving at different times. For sensitivity analysis, we separated the data into 3 groups (ARVC, ICMP, NICMP). The Kaplan–Meier curve and Cox model were fitted again to each of the 3 groups. We also re-run the analysis after the exclusion of data with a follow-up time of over 365 days, as the shortest follow-up time in the included studies was 12 months. Literature searches identified 3,181 studies imported for screening, 1,471 duplicates removed, 1,170 studies screened, 1,638 irrelevant, 72 full-text studies assessed for eligibility, 61 excluded, and 11 studies included as shown in PRISMA flow (Figure 2). The meta-analysis included a total of 11 studies with 977 patients in total. The studies varied in size, with the largest study involving 163 patients and the smallest including 45 patients. The mean follow-up duration for all studies was 31.92 months. The mean age of patients was 53.77 years, and they were predominantly male. The patient's mean left ventricular ejection fraction was 42.17%. The characteristics of the studies, the mean follow-up period, and the characteristics of the patients are described, as listed in Table 1.Table 1Study characteristicsStudyType of StudyMean agenMale (n)Previous ablationMean follow-up time, moSubstrateAblation approachMean LVEF, %Number of patients with ICDEndo-epicardialEndoEndo-epicardialEndoBai et al 20115Bai R Di Biase L Shivkumar K Mohanty P Tung R Santangeli P Saenz LC Vacca M Verma A Khaykin Y Mohanty S Burkhardt JD Hongo R Beheiry S Dello Russo A Casella M Pelargonio G Santarelli P Sanchez J Tondo C Natale A Ablation of ventricular arrhythmias in arrhythmogenic right ventricular dysplasia/cardiomyopathy: arrhythmia-free survival after endo-epicardial substrate based mapping and ablation.Circ Arrhythm Electrophysiol. 2011; 4: 478-485Crossref PubMed Scopus (202) Google ScholarProspective, Multicenter, Nonrandomized35.54967%Epi: 54%Endo: N/A36.5ARVC26235549Müssigbrodt et al 201717Müssigbrodt A Efimova E Knopp H Bertagnolli L Dagres N Richter S Husser D Bollmann A Hindricks G Arya A. Should all patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy undergo epicardial catheter ablation?.J Interv Card Electrophysiol. 2017; 48: 193-199Crossref PubMed Scopus (27) Google ScholarRetrospective, Single Center53.24568.5%Epi: 100%Endo: N/A31.3ARVC222356NPWei et al 201718Wei W Liao H Xue Y Fang X Huang J Liu Y Deng H Liang Y Liao Z Liu F Lin W Zhan X Wu S. Long-term outcomes of radio-frequency catheter ablation on ventricular tachycardias due to arrhythmogenic right ventricular cardiomyopathy: a single center experience.PLoS One. 2017; 12169863Google ScholarRetrospective, Single Center39.94868.7%Epi: 35%Endo: 0%71.4ARVC173151.411Mahida et al 201919Mahida S Venlet J Saguner AM Kumar S Baldinger SH AbdelWahab A Tedrow UB Castelletti S Pantazis A John RM McKenna WJ Lambiase PD Duru F Sapp JL Zeppenfeld K Stevenson WG. Ablation compared with drug therapy for recurrent ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy: results from a multicenter study.Heart Rhythm. 2019; 16: 536-543Abstract Full Text Full Text PDF PubMed Scopus (26) Google ScholarRetrospective, Multicenter38110 (75 ablations)83%NPNP36ARVC403555109Mathew et al 201920Mathew S Saguner AM Schenker N Kaiser L Zhang P Yashuiro Y Lemes C Fink T Maurer T Santoro F Wohlmuth P Reißmann B Heeger CH Tilz R Wissner E Rillig A Metzner A Kuck KH Ouyang F. Catheter ablation of ventricular tachycardia in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia: a sequential approach.J Am Heart Assoc. 2019; 8e010365Crossref PubMed Scopus (20) Google ScholarRetrospective, Single Center444781%NPNP50ARVC25 (+11 epicardial)45NP35Juan Acosta 201621Acosta J Fernández-Armenta J Penela D Andreu D Borras R Vassanelli F Korshunov V Perea RJ de Caralt TM Ortiz JT Fita G Sitges M Brugada J Mont L Berruezo A. Infarct transmurality as a criterion for first-line endo-epicardial substrate-guided ventricular tachycardia ablation in ischemic cardiomyopathy.Heart Rhythm. 2016; 13: 85-95Abstract Full Text Full Text PDF PubMed Scopus (61) Google ScholarProspective, Nonrandomized67.45692.2%0%0%22.5ICMP243232.5452Luigi Di Biase 201222Di Biase L Santangeli P Burkhardt DJ Bai R Mohanty P Carbucicchio C Dello Russo A Casella M Mohanty S Pump A Hongo R Beheiry S Pelargonio G Santarelli P Zucchetti M Horton R Sanchez JE Elayi CS Lakkireddy D Tondo C Natale A Endo-epicardial homogenization of the scar versus limited substrate ablation for the treatment of electrical storms in patients with ischemic cardiomyopathy.J Am Coll Cardiol. 2012; 60: 132-141Crossref PubMed Scopus (312) Google ScholarProspective, Nonrandomized629281%NPNP25ICMP43492692Ammar M Killu 201623Killu AM Mulpuru SK Al-Hijji MA Sugrue A Munger TM Hodge DO McLeod CJ Packer DL Kapa S Asirvatham SJ Friedman PA Outcomes of combined endocardial-epicardial ablation compared with endocardial ablation alone in patients who undergo epicardial access.Am J Cardiol. 2016; 118: 842-848Abstract Full Text Full Text PDF PubMed Scopus (11) Google ScholarRetrospective, Nonrandomized53.716371%80%12NICMP (49%), ICMP (12%),115484590Tung 20121Tung R Michowitz Y Yu R Mathuria N Vaseghi M Buch E Bradfield J Fujimura O Gima J Discepolo W Mandapati R Shivkumar K Epicardial ablation of ventricular tachycardia: an institutional experience of safety and efficacy.Heart Rhythm. 2013; 10: 490-498Abstract Full Text Full Text PDF PubMed Scopus (115) Google ScholarRetrospective, nonrandomized Single Center63.413686%Epi: 81%Endo: 24%12ICMP (53%) and NICMP (47%)508629.26130Arenal 202224Arenal Á Ávila P Jiménez-Candil J Tercedor L Calvo D Arribas F Fernández-Portales J Merino JL Hernández-Madrid A Fernández-Avilés FJ Berruezo A. Substrate ablation vs antiarrhythmic drug therapy for symptomatic ventricular tachycardia.J Am Coll Cardiol. 2022; 79: 1441-1453Crossref PubMed Scopus (41) Google ScholarRetrospective, Multicenter7014496%NPNP23.8ICMP-7143.771Philips et al 20126Philips B Madhavan S James C Tichnell C Murray B Dalal D Bhonsale A Nazarian S Judge DP Russell SD Abraham T Calkins H Tandri H. Outcomes of catheter ablation of ventricular tachycardia in arrhythmogenic right ventricular dysplasia/cardiomyopathy.Circ Arrhythm Electrophysiol. 2012; 5: 499-505Crossref PubMed Scopus (167) Google ScholarRetrospective, Nonrandomized38 ± 138752%NPNP88.3 ± 66.1ARVC-149NP83ARVC = arrhythmogenic right ventricular cardiomyopathy; endo = endocardial; endo-epi = endo-epicardial; ICD = implantable cardioverter-defibrillator; ICMP = ischemic cardiomyopathy; LVEF = left ventricular ejection fraction; n = number; NICMP = nonischemic cardiomyopathy; NP = not published; RF = radiofrequency. Open table in a new tab ARVC = arrhythmogenic right ventricular cardiomyopathy; endo = endocardial; endo-epi = endo-epicardial; ICD = implantable cardioverter-defibrillator; ICMP = ischemic cardiomyopathy; LVEF = left ventricular ejection fraction; n = number; NICMP = nonischemic cardiomyopathy; NP = not published; RF = radiofrequency. The median survival time for all groups combined was 1,559 days. There was a significant difference in survival between the 2 groups (Endo vs Endo + Epi) as determined by the chi-square test (p <0.01) (Table 2).Table 2The median survival timeNumber of patientsEventsMedian(days)0.95LCL0.95UCL9293441559900NANumber of patientsEventsMedian(days)0.95LCL0.95UCLEndocardial5822348717441559Endocardial plus Epicardial347110NANANA Open table in a new tab Figure 3, Figure 4 to 5 show the pooled Kaplan–Meier curve for the cumulative risk of VA recurrence in all included studies.1Tung R Michowitz Y Yu R Mathuria N Vaseghi M Buch E Bradfield J Fujimura O Gima J Discepolo W Mandapati R Shivkumar K Epicardial ablation of ventricular tachycardia: an institutional experience of safety and efficacy.Heart Rhythm. 2013; 10: 490-498Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar, 5Bai R Di Biase L Shivkumar K Mohanty P Tung R Santangeli P Saenz LC Vacca M Verma A Khaykin Y Mohanty S Burkhardt JD Hongo R Beheiry S Dello Russo A Casella M Pelargonio G Santarelli P Sanchez J Tondo C Natale A Ablation of ventricular arrhythmias in arrhythmogenic right ventricular dysplasia/cardiomyopathy: arrhythmia-free survival after endo-epicardial substrate based mapping and ablation.Circ Arrhythm Electrophysiol. 2011; 4: 478-485Crossref PubMed Scopus (202) Google Scholar, 6Philips B Madhavan S James C Tichnell C Murray B Dalal D Bhonsale A Nazarian S Judge DP Russell SD Abraham T Calkins H Tandri H. Outcomes of catheter ablation of ventricular tachycardia in arrhythmogenic right ventricular dysplasia/cardiomyopathy.Circ Arrhythm Electrophysiol. 2012; 5: 499-505Crossref PubMed Scopus (167) Google Scholar, 17Müssigbrodt A Efimova E Knopp H Bertagnolli L Dagres N Richter S Husser D Bollmann A Hindricks G Arya A. Should all patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy undergo epicardial catheter ablation?.J Interv Card Electrophysiol. 2017; 48: 193-199Crossref PubMed Scopus (27) Google Scholar, 18Wei W Liao H Xue Y Fang X Huang J Liu Y Deng H Liang Y Liao Z Liu F Lin W Zhan X Wu S. Long-term outcomes of radio-frequency catheter ablation on ventricular tachycardias due to arrhythmogenic right ventricular cardiomyopathy: a single center experience.PLoS One. 2017; 12169863Google Scholar, 19Mahida S Venlet J Saguner AM Kumar S Baldinger SH AbdelWahab A Tedrow UB Castelletti S Pantazis A John RM McKenna WJ Lambiase PD Duru F Sapp JL Zeppenfeld K Stevenson WG. Ablation compared with drug therapy for recurrent ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy: results from a multicenter study.Heart Rhythm. 2019; 16: 536-543Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 20Mathew S Saguner AM Schenker N Kaiser L Zhang P Yashuiro Y Lemes C Fink T Maurer T Santoro F Wohlmuth P Reißmann B Heeger CH Tilz R Wissner E Rillig A Metzner A Kuck KH Ouyang F. Catheter ablation of ventricular tachycardia in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia: a sequential approach.J Am Heart Assoc. 2019; 8e010365Crossref PubMed Scopus (20) Google Scholar, 21Acosta J Fernández-Armenta J Penela D Andreu D Borras R Vassanelli F Korshunov V Perea RJ de Caralt TM Ortiz JT Fita G Sitges M Brugada J Mont L Berruezo A. Infarct transmurality as a criterion for first-line endo-epicardial substrate-guided ventricular tachycardia ablation in ischemic cardiomyopathy.Heart Rhythm. 2016; 13: 85-95Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 22Di Biase L Santangeli P Burkhardt DJ Bai R Mohanty P Carbucicchio C Dello Russo A Casella M Mohanty S Pump A Hongo R Beheiry S Pelargonio G Santarelli P Zucchetti M Horton R Sanchez JE Elayi CS Lakkireddy D Tondo C Natale A Endo-epicardial homogenization of the scar versus limited substrate ablation for the treatment of electrical storms in patients with ischemic cardiomyopathy.J Am Coll Cardiol. 2012; 60: 132-141Crossref PubMed Scopus (312) Google Scholar, 23Killu AM Mulpuru SK Al-Hijji MA Sugrue A Munger TM Hodge DO McLeod CJ Packer DL Kapa S Asirvatham SJ Friedman PA Outcomes of combined endocardial-epicardial ablation compared with endocardial ablation alone in patients who undergo epicardial access.Am J Cardiol. 2016; 118: 842-848Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 24Arenal Á Ávila P Jiménez-Candil J Tercedor L Calvo D Arribas F Fernández-Portales J Merino JL Hernández-Madrid A Fernández-Avilés FJ Berruezo A. Substrate ablation vs antiarrhythmic drug therapy for symptomatic ventricular tachycardia.J Am Coll Cardiol. 2022; 79: 1441-1453Crossref PubMed Scopus (41) Google Scholar The pooled analysis of all studies revealed that patients who underwent the Endo-epi procedure had a significantly lower risk of VA recurrence compared with those who underwent Endo alone, with a hazard ratio (HR) of 0.69% and 95% confidence interval (CI) of 0.55 to 0.87, p <0.00169. The analysis included data from 929 patients (Endo: 582 patients; Endo-epi: 347 patients) from 11 studies with a median follow-up of 5.47 years.Figure 4Kaplan–Meier curve with a number at risk table for all patients.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 5Cumulative hazard curve.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Conditional survival analysis showed that after 5 years and free of arrhythmia recurrence, there was no more risk of arrhythmia recurrence. However, the VT recurrence probabilities were higher in the group treated with Endo alone, and patients treated with Endo-only reached year 5 with a high probability of VT recurrence (Figure 6, Figure 7 to 8).Figure 7Conditional survival estimates of surviving to a variety of different time points given that the subject has already survived for 0 years.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 8Conditional survival estimates of surviving to a variety of different time points given that the subject has already survived for 0 years.View Large Image Figure ViewerDownload Hi-res image Download (PPT) After day 1000, there was no difference in the VT survival recurrence between the patients who underwent Endo-epi and those who underwent Endo alone, with an HR of 1.00, 4.22, and p >0.9 (Figure 9). The absence of any significant difference in long-term treatment outcomes between Endo-epi and Endo alone underscores the importance of considering this as a cornerstone in future treatment plans. The sensitivity analysis of the subtypes of the disease showed that patients with ARVC who underwent Endo-epi procedures had a significantly lower risk of VA recurrence, with an HR of 0.54 and p <0.00047. Patients with ICM who underwent Endo-epi procedures had a significantly lower risk of VA recurrence, with an HR of 0.835, 0.55 to 0.87, and p <0.021. However, there was no significant difference in the risk of VA recurrence between the Endo-epi and Endo groups for patients with nonischemic cardiomyopathies, with an HR of 0.440, 0.55 to 0.87, and p <0.33 (Figure 10, Figure 11 to 12).Figure 11Pooled Kaplan-Meier curves showing the cumulative risk between the Endo-epi and Endo group patients with ICM.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 12Pooled Kaplan-Meier curves showing the cumulative risk between the Endo-epi and Endo group patients with NICM.View Large Image Figure ViewerDownload Hi-res image Download (PPT) The overall observed heterogeneity in all studies was not significant, with a p <0.51 and an I² value of 0%, indicating no significant variability in the included studies (Figure 13). This is the first meta-analysis using reconstructed time-to-event data to compare Endo-epi CA versus Endo ablation alone. The results of the meta-analysis showed that patients who underwent the Endo-epi procedure had a significantly lower risk of VA recurrence compared with those treated with Endo CA alone. Moreover, our analysis showed that there was no significant heterogeneity in the included studies, which increases the reliability of the meta-analysis findings. The analysis of subgroups based on the type of cardiomyopathy revealed that patients with ARVC and ICM benefited significantly from Endo-epi CA in terms of reducing the risk of VA recurrence. However, there was no significant difference in VA recurrence between Endo-epi and Endo CA alone in patients with non-ICM. The analysis of conditional survival demonstrated that patients who remained free of VA recurrence for 5 years after the procedure had a very low probability of developing VA recurrence thereafter. This finding suggests that the long-term success rate of Endo-epi CA in reducing VA recurrence is promising, especially in patients who remain arrhythmia-free for at least 5 years. Our study goes along with the previous meta-analysis published by Cardoso et al25Cardoso FR Assis and A D’Avila, Endo-epicardial vs endocardial-only catheter ablation of ventricular tachycardia: A meta-analysis.J Cardiovasc Electrophysiol. 2019; 30: 1537-1548Crossref PubMed Scopus (5) Google Scholar and adding new important evidenced points to the literature in the long-term follow-up of the included patients: (1) The addition of recently published studies; (2) When it comes to time-to-event data, using Kaplan–Meier curves with longer follow-ups is more accurate, precise, and reliable than using incidence rate ratios; (3) Showing that there is no difference between Endo-epi ablation versus Endo ablation alone after passing 1,000 days which is a new and important ablation. Recurrent VT patients can benefit from VT ablation as a therapeutic alternative. According to the Ventricular Tachycardia Ablation versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease trial, patients who underwent VT ablation who had ICM and implantable cardioverter-defibrillators (ICDs) with recurrent VT despite being treated with AAD experienced a 30% relative risk reduction in death, VT storm, or appropriate ICD shock at a mean follow-up of 28 months compared with patients receiving only escalation of AAD therapy. There are however limits to CA's efficacy in treating VT. The Ventricular Tachycardia Ablation versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease study found that more than 40% of patients who underwent CA had an appropriate ICD shock during follow-up, and about a quarter had VT storms longer than 30 days after the procedure.26Sapp JL Wells GA Parkash R Stevenson WG Blier L Sarrazin J-F Thibault B Rivard L Gula L Leong-Sit P Essebag V Nery PB Tung SK Raymond J-M Sterns LD Veenhuyzen GD Healey JS Redfearn D Roux J-F Tang ASL Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs.N Engl J Med. 2016; 375: 111-121Crossref PubMed Google Scholar It is difficult to identify the location and anatomy of the arrhythmogenic scar during VT CA. The location of epicardial or intramyocardial reentry circuits that are substrates to monomorphic VT may limit the efficacy of standard endocardial mapping and ablation. A physician identifies patients who can benefit from CA through epicardial access (1) the likelihood of epicardial VT depending on the substrate beneath (e.g., Brugada's syndrome patients may benefit from epicardial ablation); (2) electrocardiography; (3) imaging studies determining scar location; and (4) intraoperative mapping. Although CA techniques differ significantly between centers worldwide, it is common practice to attempt Endo-only ablations first, followed by Endo-epi ablations if the Endo ablation fails. Herein comes the importance of the meta-analysis that shows which is better. To sum up, our study favors Endo-epi ablations to be done as first-line treatment. The study has 2 main limitations. First, all the included studies were nonrandomized trials, which limits the strength of the evidence. Therefore, randomized controlled trials are needed to further investigate the efficacy of Endo-epi CA. Second, the study could not include studies that did not have Kaplan–Meier graphs, which may have resulted in some studies being excluded, potentially affecting the overall findings. Nonetheless, the study provides a comprehensive analysis of the available literature using Kaplan–Meier curves with longer follow-ups, which is more accurate, precise, and reliable than using incidence rate ratios. This study provides evidence that Endo-epi CA is more effective than Endo CA alone in reducing the risk of VA recurrence in patients with structural heart disease. Overall, whereas the study provides valuable insights into the effectiveness of Endo-epi CA in reducing the risk of ventricular arrhythmia recurrence in patients with structural heart disease, its limitations highlight the need for further research to confirm these findings.