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Systematic review and meta-analysis of catheter ablation of ventricular tachycardia in ischemic heart disease

      Background

      Patients with ischemic heart disease (IHD) are at risk for ventricular tachycardia (VT). Catheter ablation (CA) may reduce this risk.

      Objective

      To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) of CA of VT in patients with IHD.

      Methods

      Literature searches of MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic Reviews (CDSR) were performed from January 2000 through April 2018 to identify RCTs comparing a strategy of CA vs no ablation in patients with IHD and an implantable cardioverter defibrillator (ICD). Outcomes of interest included appropriate ICD therapies, appropriate ICD shocks, VT storm, recurrent VT/ventricular fibrillation (VF), cardiac hospitalizations, and all-cause mortality. Using an inverse variance random-effects model, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each endpoint.

      Results

      A total of 5 RCTs (N = 635 patients) were included, with a duration of follow-up ranging from 6 months to 27.9 months. Patients who underwent CA experienced decreased odds of appropriate ICD therapies (OR 0.49; 95% CI 0.28–0.87), appropriate ICD shocks (OR 0.52; 95% CI 0.28–0.96), VT storm (OR 0.64; 95% CI 0.43–0.95), and cardiac hospitalization (OR 0.67; 95% CI 0.46–0.97) vs those who did not undergo ablation. There was no evidence of a benefit for recurrent VT/VF (OR 0.87; 95% CI 0.41–1.85), although this endpoint was not reported in all trials, or for all-cause mortality (OR 0.89; 95% CI 0.60–1.34).

      Conclusion

      In this systematic review and meta-analysis of RCTs, CA was associated with a significant reduction in the odds of appropriate ICD therapies, appropriate ICD shocks, VT storm, and cardiac hospitalizations in patients with IHD.

      Keywords

      Abbreviations:

      AAD (antiarrhythmic drug), ATP (antitachycardia pacing), CA (catheter ablation), CI (confidence interval), ERC (Evidence Review Committee), ICD (implantable cardioverter defibrillator), IHD (ischemic heart disease), MI (myocardial infarction), OR (odds ratio), RCT (randomized controlled trial), VF (ventricular fibrillation), VT (ventricular tachycardia)
      Document Reviewers: Samuel J. Asirvatham, MD, FHRS; Sabine Ernst, MD, PhD.

      Background

      Patients with ischemic heart disease (IHD) are at increased risk of incident or recurrent ventricular tachycardia (VT), ventricular fibrillation (VF), and sudden cardiac death. Implantable cardioverter defibrillators (ICDs) are the mainstay of treatment to reduce the incidence of sudden cardiac death by terminating ventricular arrhythmias either by antitachycardia pacing (ATP) or by delivering a shock.
      • Tracy C.M.
      • Epstein A.E.
      • Darbar D.
      • et al.
      2012 ACCF/AHA/HRS focused update of the 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
      • Pedersen C.T.
      • Kay G.N.
      • Kalman J.
      • et al.
      EHRA/HRS/APHRS expert consensus on ventricular arrhythmias.
      • Al-Khatib S.M.
      • Stevenson W.G.
      • Ackerman M.J.
      • et al.
      2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.
      However, ICD shocks, whether appropriate or inappropriate, can have negative effects on patients’ quality of life
      • Schron E.B.
      • Exner D.V.
      • Yao Q.
      • et al.
      Quality of life in the antiarrhythmics versus implantable defibrillators trial: impact of therapy and influence of adverse symptoms and defibrillator shocks.
      • Irvine J.
      • Dorian P.
      • Baker B.
      • et al.
      Quality of life in the Canadian Implantable Defibrillator Study (CIDS).
      • Kamphuis H.C.
      • de Leeuw J.R.
      • Derksen R.
      • Hauer R.N.
      • Winnubst J.A.
      Implantable cardioverter defibrillator recipients: quality of life in recipients with and without ICD shock delivery: a prospective study.
      • Passman R.
      • Subacius H.
      • Ruo B.
      • et al.
      Implantable cardioverter defibrillators and quality of life: results from the Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation study.
      and are associated with an increased risk of subsequent mortality.
      • Poole J.E.
      • Johnson G.W.
      • Hellkamp A.S.
      • et al.
      Prognostic importance of defibrillator shocks in patients with heart failure.
      • Moss A.J.
      • Greenberg H.
      • Case R.B.
      • et al.
      Long-term clinical course of patients after termination of ventricular tachyarrhythmia by an implanted defibrillator.
      Thus, therapies that can effectively reduce the risk of ICD shocks are of great importance. Catheter ablation (CA) of VT has become established as a means to treat VT and prevent recurrence.
      • Aliot E.M.
      • Stevenson W.G.
      • Almendral-Garrote J.M.
      • et al.
      EHRA/HRS Expert consensus on catheter ablation of ventricular arrhythmias: developed in a partnership with the European Heart Rhythm Association (EHRA), a Registered Branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA).
      Several randomized controlled trials (RCTs) have been conducted comparing CA with other strategies, such as antiarrhythmic drug (AAD) therapy or control, in patients with IHD.
      The Heart Rhythm Society (HRS), the European Heart Rhythm Association (EHRA), the Asia Pacific Heart Rhythm Society (APHRS), and the Latin American Heart Rhythm Society (LAHRS), in collaboration with the American Heart Association (AHA), the American College of Cardiology (ACC), the Japanese Heart Rhythm Society (JHRS), the Brazilian Society of Cardiac Arrhythmias (Sociedade Brasileira de Arritmias Cardíacas [SOBRAC]), and the Pediatric and Congenital Electrophysiology Society (PACES), appointed a writing committee to draft an expert consensus statement to update the 2009 EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias.
      • Aliot E.M.
      • Stevenson W.G.
      • Almendral-Garrote J.M.
      • et al.
      EHRA/HRS Expert consensus on catheter ablation of ventricular arrhythmias: developed in a partnership with the European Heart Rhythm Association (EHRA), a Registered Branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA).
      The Scientific and Clinical Documents Committee of HRS recognized the need for a high-quality systematic review and meta-analysis of the published literature by an Evidence Review Committee (ERC) to inform recommendations. Such an effort must be directed toward areas where key clinical questions can be formed and where published data exist. Here, we report the findings of this effort, with the purpose of evaluating the use of CA in preventing VT events in patients with IHD through a systematic review and meta-analysis. For transparency, ERC members’ comprehensive disclosure information is available in Appendix 1, as is comprehensive disclosure information for the peer reviewers in Appendix 2.

      Methods

      This meta-analysis conforms to standard guidelines and is written in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      PRISMA Group
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
      The PICOT format (P = population, I = intervention, C = comparator, O = outcome, T = timing, S = setting)
      Institute of Medicine (US)
      Committee on Standards for Systematic Reviews of Comparative Effectiveness Research. Finding what works in health care: standards for systematic reviews.
      was used to derive the key clinical question. This question was, “In adults with a history of sustained ventricular tachycardia and ischemic cardiomyopathy, what are the effectiveness and harms of catheter ablation compared to other interventions?”

       Data Sources and Search Strategy

      We systematically searched MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic Reviews (CDSR) from January 2000 through April 2018 to identify RCTs comparing a strategy of CA vs no ablation in patients with IHD, an ICD, and a history of VT. The following Medical Subject Headings (MeSH) and keywords were used: ventricular tachycardia, ventricular arrhythmia, ventricular fibrillation, catheter ablation, antiarrhythmic agents, and antiarrhythmic drug. All searches were limited to full-text articles published in English. A manual search of references from included studies was also performed.

       Study Selection

      For the title, abstract, and full-text article review, two investigators independently examined all potentially relevant citations and articles in a parallel manner, using predefined inclusion and exclusion criteria. Studies were included in this systematic review and meta-analysis if they 1) were RCTs; 2) enrolled adults (>18 years of age); 3) enrolled patients with IHD implanted with an ICD and a history of spontaneous VT or syncope with inducible VT; 4) had at least one CA treatment group; and 5) had outcomes of interest data suitable for pooling. Studies were excluded if they were case reports, reviews, editorials, or non-English language publications. The outcomes of interest included appropriate ICD therapies (ICD shock or ATP), appropriate ICD shocks, VT storm (defined as ≥3 shocks within 24 hours), recurrent VT/VF, cardiac hospitalizations, and all-cause mortality.

       Data Extraction

      For each study, two investigators used a standardized data abstraction tool to extract all the relevant and specific information. Disagreements were resolved by consensus. Information collected from each study included author, year of publication, interventions, sample size, key inclusion criteria, months of follow-up, class I or III AADs, other cardiovascular drugs, time to last myocardial infarction (MI), prior revascularization, and pertinent patient characteristics. Study authors were contacted for clarification of information not covered in the publication. All included studies are multicenter prospective RCTs. The risk of bias for each study was independently assessed by two investigators using the Cochrane Risk of Bias Tool.
      • Higgins J.P.
      • Altman D.G.
      • Gøtzsche P.C.
      • et al.
      The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials.
      This tool includes 7 items covering the following domains: selection bias due to inadequate generation of a randomized sequence, or inadequate concealment of allocations prior to assignment; performance bias due to knowledge of the allocated interventions by participants and personnel during the study; detection bias due to knowledge of the allocated interventions by outcome assessors; attrition bias due to amount, nature, or handling of incomplete outcome data; reporting bias due to selective outcome reporting; and other bias due to problems not previously covered.
      • Higgins J.P.
      • Altman D.G.
      • Gøtzsche P.C.
      • et al.
      The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials.

       Statistical Analysis

      All outcome data were pooled using an inverse variance random-effects model producing odds ratios (ORs) and accompanying 95% confidence intervals (CIs) for each endpoint, with between-study heterogeneity (τ2) calculated using the Paule-Mandel estimator. The I2 statistic was calculated to estimate the percentage of variability in the treatment estimate attributable to statistical heterogeneity between studies, with a value >50% considered substantial.
      • Higgins J.P.
      • Thomas S.G.
      • Deeks J.J.
      • Altman D.G.
      Measuring inconsistency in meta-analyses.
      Small study effects, including publication bias, were not examined, given fewer than 10 eligible studies were identified. All analyses were performed using the ‘meta’ package in R (version 3.4.3; the R Project for Statistical Computing).
      In order to better quantify the effects of CA on our outcomes of interest, we conducted a random-effects meta-regression via iterative maximum likelihood.
      • Baker W.L.
      • White C.M.
      • Cappelleri J.C.
      • Kluger J.
      • Coleman C.I.
      Health Outcomes, Policy, and Economics (HOPE) Collaborative Group
      Understanding heterogeneity in meta-analysis: the role of meta-regression.
      An analysis evaluating the impact of baseline amiodarone therapy on each of the outcomes of interest was performed. The percentage of patients administered baseline amiodarone was used to conduct meta-regression to examine whether baseline amiodarone therapy altered the effectiveness of CA.

      Results

      The inclusion and exclusion of citations and articles identified through our systematic literature search is illustrated in Figure 1. A total of 5 studies evaluating the use of CA in patients with IHD and an ICD published between 2007 and 2017 were included in the analysis (Table 1).
      • Kuck K.H.
      • Tilz R.R.
      • Deneke T.
      • et al.
      Impact of substrate modification by catheter ablation on implantable cardioverter-defibrillator interventions in patients with unstable ventricular arrhythmias and coronary artery disease: results from the multicenter randomized controlled SMS (Substrate Modification Study).
      • Sapp J.L.
      • Wells G.A.
      • Parkash R.
      • et al.
      Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs.
      • Al-Khatib S.M.
      • Daubert J.P.
      • Anstrom K.J.
      • et al.
      Catheter ablation for ventricular tachycardia in patients with an implantable cardioverter defibrillator (CALYPSO) pilot trial.
      • Kuck K.H.
      • Schaumann A.
      • Eckardt L.
      • et al.
      Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary artery disease (VTACH): a multicentre randomised controlled trial.
      • Reddy V.Y.
      • Reynolds M.R.
      • Neuzil P.
      • et al.
      Prophylactic catheter ablation for the prevention of defibrillator therapy.
      All included studies were multicenter RCTs. Individual study sample sizes ranged from 27 patients to 259 patients. The mean patient age ranged from 64 years to 68 years, and the duration of follow-up was 6–27.9 months. The time to last MI ranged from <1 year to 15.7 years. The use of AADs varied between studies. The Substrate Mapping and Ablation in Sinus Rhythm to Halt Ventricular Tachycardia (SMASH-VT) study excluded patients treated with class I or III antiarrhythmics
      • Reddy V.Y.
      • Reynolds M.R.
      • Neuzil P.
      • et al.
      Prophylactic catheter ablation for the prevention of defibrillator therapy.
      ; 3 studies included between 32% and 37% of patients treated with amiodarone and sotalol
      • Kuck K.H.
      • Tilz R.R.
      • Deneke T.
      • et al.
      Impact of substrate modification by catheter ablation on implantable cardioverter-defibrillator interventions in patients with unstable ventricular arrhythmias and coronary artery disease: results from the multicenter randomized controlled SMS (Substrate Modification Study).
      • Al-Khatib S.M.
      • Daubert J.P.
      • Anstrom K.J.
      • et al.
      Catheter ablation for ventricular tachycardia in patients with an implantable cardioverter defibrillator (CALYPSO) pilot trial.
      • Kuck K.H.
      • Schaumann A.
      • Eckardt L.
      • et al.
      Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary artery disease (VTACH): a multicentre randomised controlled trial.
      ; and the Ventricular Tachycardia Ablation versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease (VANISH) trial required patients to have received background amiodarone or another class I or class III AAD within the previous 6 months.
      • Sapp J.L.
      • Wells G.A.
      • Parkash R.
      • et al.
      Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs.
      ICD programming was standardized in each study; however, recommendations varied between studies. Three studies reported the incidence of ICD therapies,
      • Kuck K.H.
      • Tilz R.R.
      • Deneke T.
      • et al.
      Impact of substrate modification by catheter ablation on implantable cardioverter-defibrillator interventions in patients with unstable ventricular arrhythmias and coronary artery disease: results from the multicenter randomized controlled SMS (Substrate Modification Study).
      • Kuck K.H.
      • Schaumann A.
      • Eckardt L.
      • et al.
      Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary artery disease (VTACH): a multicentre randomised controlled trial.
      • Reddy V.Y.
      • Reynolds M.R.
      • Neuzil P.
      • et al.
      Prophylactic catheter ablation for the prevention of defibrillator therapy.
      4 studies reported ICD shocks and VT storm,
      • Baker W.L.
      • White C.M.
      • Cappelleri J.C.
      • Kluger J.
      • Coleman C.I.
      Health Outcomes, Policy, and Economics (HOPE) Collaborative Group
      Understanding heterogeneity in meta-analysis: the role of meta-regression.
      • Kuck K.H.
      • Tilz R.R.
      • Deneke T.
      • et al.
      Impact of substrate modification by catheter ablation on implantable cardioverter-defibrillator interventions in patients with unstable ventricular arrhythmias and coronary artery disease: results from the multicenter randomized controlled SMS (Substrate Modification Study).
      • Al-Khatib S.M.
      • Daubert J.P.
      • Anstrom K.J.
      • et al.
      Catheter ablation for ventricular tachycardia in patients with an implantable cardioverter defibrillator (CALYPSO) pilot trial.
      • Kuck K.H.
      • Schaumann A.
      • Eckardt L.
      • et al.
      Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary artery disease (VTACH): a multicentre randomised controlled trial.
      all studies reported all-cause mortality,
      • Kuck K.H.
      • Tilz R.R.
      • Deneke T.
      • et al.
      Impact of substrate modification by catheter ablation on implantable cardioverter-defibrillator interventions in patients with unstable ventricular arrhythmias and coronary artery disease: results from the multicenter randomized controlled SMS (Substrate Modification Study).
      • Sapp J.L.
      • Wells G.A.
      • Parkash R.
      • et al.
      Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs.
      • Al-Khatib S.M.
      • Daubert J.P.
      • Anstrom K.J.
      • et al.
      Catheter ablation for ventricular tachycardia in patients with an implantable cardioverter defibrillator (CALYPSO) pilot trial.
      • Kuck K.H.
      • Schaumann A.
      • Eckardt L.
      • et al.
      Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary artery disease (VTACH): a multicentre randomised controlled trial.
      • Reddy V.Y.
      • Reynolds M.R.
      • Neuzil P.
      • et al.
      Prophylactic catheter ablation for the prevention of defibrillator therapy.
      4 studies reported hospitalizations for cardiac cause,
      • Baker W.L.
      • White C.M.
      • Cappelleri J.C.
      • Kluger J.
      • Coleman C.I.
      Health Outcomes, Policy, and Economics (HOPE) Collaborative Group
      Understanding heterogeneity in meta-analysis: the role of meta-regression.
      • Kuck K.H.
      • Tilz R.R.
      • Deneke T.
      • et al.
      Impact of substrate modification by catheter ablation on implantable cardioverter-defibrillator interventions in patients with unstable ventricular arrhythmias and coronary artery disease: results from the multicenter randomized controlled SMS (Substrate Modification Study).
      • Sapp J.L.
      • Wells G.A.
      • Parkash R.
      • et al.
      Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs.
      • Al-Khatib S.M.
      • Daubert J.P.
      • Anstrom K.J.
      • et al.
      Catheter ablation for ventricular tachycardia in patients with an implantable cardioverter defibrillator (CALYPSO) pilot trial.
      and 3 studies reported recurrent VT/VF.
      • Kuck K.H.
      • Tilz R.R.
      • Deneke T.
      • et al.
      Impact of substrate modification by catheter ablation on implantable cardioverter-defibrillator interventions in patients with unstable ventricular arrhythmias and coronary artery disease: results from the multicenter randomized controlled SMS (Substrate Modification Study).
      • Al-Khatib S.M.
      • Daubert J.P.
      • Anstrom K.J.
      • et al.
      Catheter ablation for ventricular tachycardia in patients with an implantable cardioverter defibrillator (CALYPSO) pilot trial.
      • Kuck K.H.
      • Schaumann A.
      • Eckardt L.
      • et al.
      Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary artery disease (VTACH): a multicentre randomised controlled trial.
      Trial investigators provided additional outcome results: appropriate ATP or appropriate shocks in VANISH; and appropriate ATP or appropriate shocks, VT storm, and cardiac hospitalizations in Catheter Ablation for Ventricular Tachycardia in Patients with an Implantable Cardioverter Defibrillator (CALYPSO). The majority of studies were at low risk for selection bias, attrition bias, and reporting bias. All studies were at high risk of performance bias due to a lack of blinding of participants and personnel, given the nature of patients being randomized to receiving a procedure or no procedure. Two studies were determined to be at high risk of other biases due to their study design comparing patients who received an ablation with those who received changes in AAD therapy.
      • Sapp J.L.
      • Wells G.A.
      • Parkash R.
      • et al.
      Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs.
      • Al-Khatib S.M.
      • Daubert J.P.
      • Anstrom K.J.
      • et al.
      Catheter ablation for ventricular tachycardia in patients with an implantable cardioverter defibrillator (CALYPSO) pilot trial.
      Additionally, 2 studies were determined to possess a high risk of other biases due to substantial crossover between randomized groups throughout the study (Figure 2).
      • Al-Khatib S.M.
      • Daubert J.P.
      • Anstrom K.J.
      • et al.
      Catheter ablation for ventricular tachycardia in patients with an implantable cardioverter defibrillator (CALYPSO) pilot trial.
      • Kuck K.H.
      • Schaumann A.
      • Eckardt L.
      • et al.
      Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary artery disease (VTACH): a multicentre randomised controlled trial.
      Table 1Baseline characteristics of included studies
      Study

      Year

      N
      Interventions (N)Key inclusion criteriaActual FU (months)LVEFNYHA classAge, years (range of means)Other CV drugsClass I or III AADsTime to last MI, yearsPrior revascularization
      SMS

      2017

      N = 111
      Catheter ablation (N = 54)

      No ablation (N = 57)
      CAD, LVEF ≤40%, and clinically unstable spontaneous VT; or cardiac arrest or syncope with unstable VT inducible at electrophysiological study27.6 ± 13.2≤30 = 45%

      >30 = NR
      I–III = 100%

      IV = 0%
      66–68ACEI/ARB = 95%

      BB = 91%

      Digoxin = NR

      Diuretic = NR

      Statin = NR

      ASA = NR

      AC = NR
      32% (amiodarone)9.8 ± 7.3PCI = 46%

      Surgical = 42%
      VANISH

      2016

      N = 259
      Catheter ablation + background of AAD (N = 132)

      No ablation + escalation of AAD (N = 127)
      Previous MI; undergone placement of an ICD; had an episode of VT during treatment with amiodarone or another class I or III AAD within the previous 6 months27.9 ± 17.131 (mean)I = 24%

      II = 53%

      III = 24%

      IV = 0%
      67–70ACEI/ARB = 88%

      BB = 95%

      Digoxin = 20%

      Diuretic = 69%

      Statin = NR

      ASA = 71%

      AC = 43%
      100%15.7PCI = 43%

      CABG = 46%
      CALYPSO

      2015

      N = 27
      Catheter ablation + no AAD (N = 13)

      No ablation + AAD (N = 14)
      ICD implanted for primary or secondary prevention indication; IHD; ≥1 documented ICD shock or ≥ 3 ATP therapies within 6 months for monomorphic VT92% completed 3 months; 71% completed 6 months23%–25% (range of medians)I = 19%

      II = 30%

      III = 15%

      IV = 0%
      64–65ACEI/ARB = 93%

      BB = 93%

      Digoxin = NR

      Diuretic = NR

      Statin = 85%

      ASA = NR

      AC = NR
      37% (amiodarone and sotalol)<1 year = 7%

      1–2 years = 0%

      >2 years = 41%

      Unknown = 48%
      PCI = 52%

      CABG = 59%
      VTACH

      2010

      N = 110
      Catheter ablation (N = 54)

      No ablation (N = 56)
      Indication for ICD as secondary prevention after documented stable clinical VT without a reversible cause; CAD; previous MI; and LVEF ≤50%22.5 ± 9≤30 = 40%

      >30 = 60%
      NR64–68ACEI/ARB = NR

      BB = 75%

      Digoxin = NR

      Diuretic = NR

      Statin = NR

      ASA = NR

      AC = NR
      35% (amiodarone)12.9 ± 8.2PTCA = 47%

      Surgical = 45%
      SMASH-VT

      2007

      N = 128
      Catheter ablation (N = 64)

      No ablation (N = 64)
      MI ≥1 month; undergone a planned or recent (within 6 months) implantation of a defibrillator for VF, hemodynamically unstable VT, or syncope with inducible VT; class I or class III AAD-naïve22.5 ± 5.5≤30 = 52%

      >30 = 48%
      I/II = 80%

      III/IV = 20%
      66–67ACEI/ARB = 92%

      BB = 96%

      Digoxin = NR

      Diuretic = NR

      Statin = 59%

      ASA = 71%

      AC = NR
      0%7.9–8.8 (range of means)PTCA/CABG = 67%
      AAD = antiarrhythmic drug; AC = anticoagulant; ACEI = angiotensin converting enzyme inhibitor; ARB = angiotensin II receptor blocker; ASA = aspirin; ATP = antitachycardia pacing; BB = beta blocker; CABG = coronary artery bypass grafting; CAD = coronary artery disease; CV = cardiovascular; FU = follow-up; ICD = implantable cardioverter defibrillator; IHD = ischemic heart disease; LVEF = left ventricular ejection fraction; MI = myocardial infarction; N = number; NR = not reported; NYHA = New York Heart Association; PCI = percutaneous coronary intervention; PTCA = percutaneous transluminal coronary angioplasty; SMASH-VT = Substrate Mapping and Ablation in Sinus Rhythm to Halt Ventricular Tachycardia; VF = ventricular fibrillation; VT = ventricular tachycardia.
      Upon meta-analysis, patients who were randomized to CA had decreased odds of appropriate ICD therapies (OR 0.49; 95% CI 0.28–0.87), appropriate ICD shocks (OR 0.52; 95% CI 0.28–0.96), VT storm (OR 0.64; 95% CI 0.43–0.95), and cardiac hospitalizations (OR 0.67; 95% CI 0.46–0.97) vs those who did not undergo CA. There was no evidence of a significant difference in the odds of recurrent VT/VF (OR 0.87; 95% CI 0.41–1.85) or all-cause mortality (OR 0.89; 95% CI 0.60–1.34) between the ablation and no ablation groups (Figures 3 and 4).
      Figure thumbnail gr3
      Figure 3Pooled odds of appropriate ICD therapies (A), appropriate ICD shocks (B), and all-cause mortality (C). ABL = ablation; CI = confidence interval; ICD = implantable cardioverter defibrillator; OR = odds ratio.
      Figure thumbnail gr4
      Figure 4Pooled odds of VT storm (A), recurrent VT/VF (B), and cardiac hospitalizations (C). ABL = ablation; CI = confidence interval; OR = odds ratio; VF = ventricular fibrillation; VT = ventricular tachycardia.

       Post Hoc Sensitivity Analysis and Meta-Regression

      The VANISH and CALYPSO trials differed from the other studies included in this meta-analysis in that they compared CA with AAD therapy. Patients in the VANISH trial were randomly assigned to receive either CA (ablation group) with continuation of baseline AADs or escalated AAD therapy (escalated-therapy group).
      • Sapp J.L.
      • Wells G.A.
      • Parkash R.
      • et al.
      Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs.
      The CALYPSO trial was a comparison of AADs with CA.
      • Al-Khatib S.M.
      • Daubert J.P.
      • Anstrom K.J.
      • et al.
      Catheter ablation for ventricular tachycardia in patients with an implantable cardioverter defibrillator (CALYPSO) pilot trial.
      Due to the differences in trial design, we ran a sensitivity analysis with the removal of these two trials. Upon analysis, the removal of the VANISH and CALYPSO trials decreased the between-study heterogeneity (I2 = 0% vs 65%) and showed a greater effect of ablation on appropriate ICD shocks (OR 0.38; 95% CI 0.22–0.64). The removal of these two studies resulted in lower odds of VT storm (OR 0.55; 95% CI 0.30–1.01), cardiac hospitalizations (OR 0.58; 95% CI 0.29–1.15), recurrent VT/VF (OR 0.71; 95% CI 0.34–1.50), and all-cause mortality (OR 0.77; 95% CI 0.41–1.46); however, statistical significance was lost for some outcomes, likely due to type 2 error (Figure 5). A random-effects meta-regression showed no significant association between baseline amiodarone therapy and appropriate ICD therapies (P = .27), VT storm (P = .35), cardiac hospitalizations (P = .65), or all-cause mortality (P = .43). There was, however, a significant association between baseline amiodarone therapy and appropriate ICD shocks (P <.01). A negative association was seen: as the percentage of patients on concomitant AAD therapy increased, the effectiveness of CA in preventing appropriate ICD shocks decreased (Figure 6).
      Figure thumbnail gr5
      Figure 5Sensitivity analysis of appropriate ICD shocks (A), VT storm (B), cardiac hospitalizations (C), recurrent VT/VF (D), and all-cause mortality (E). ABL = ablation; CI = confidence interval; ICD = implantable cardioverter defibrillator; OR = odds ratio; VF = ventricular fibrillation; VT = ventricular tachycardia.
      Figure thumbnail gr6
      Figure 6Random-effects meta-regression evaluating relationship between percentage of concomitant AAD and effectiveness of catheter ablation on reduction of appropriate ICD shocks. The circles represent individual studies, with the size of the circle proportional to the weight of each study. The line represents the best fit line describing the relationship between the percent AAD use in each study (x-axis) and the effect on appropriate ICD shocks (y-axis). As the percentage of AAD users in the studies increased, the beneficial effect of catheter ablation on reducing appropriate ICD shocks decreased. AAD = antiarrhythmic drug; ICD = implantable cardioverter defibrillator.

       Adverse Events

      Adverse events were variably defined, and some protocols mandated ICD implantation at or soon after randomization, making attribution of adverse events to the ablation procedure or the ICD implantation procedure difficult. However, adverse events related to the ablation procedure occurred in 30 of 315 (9.5%) patients in the ablation arms of the included trials. Adverse events in the control arms were not reported uniformly due to variations in control strategies. In the two trials that directly compared ablation versus AAD therapy, adverse events were more common in the AAD arm than in the ablation arm.
      • Sapp J.L.
      • Wells G.A.
      • Parkash R.
      • et al.
      Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs.
      • Al-Khatib S.M.
      • Daubert J.P.
      • Anstrom K.J.
      • et al.
      Catheter ablation for ventricular tachycardia in patients with an implantable cardioverter defibrillator (CALYPSO) pilot trial.

      Discussion

      In this systematic review of the literature and a meta-analysis of 5 RCTs, we found that CA reduced the likelihood of appropriate ICD therapies, appropriate ICD shocks, VT storm, and cardiac hospitalization vs controls. In a sensitivity analysis, excluding the 2 studies that specifically randomized patients to CA versus AAD, the magnitude of such reductions was increased, although CIs also widened. This result might suggest an effect of AAD in reducing the risk of VT recurrence and ICD therapies, as found in earlier pharmacotherapy trials.
      • Pacifico A.
      • Hohnloser S.H.
      • Williams J.H.
      • et al.
      Prevention of implantable-defibrillator shocks by treatment with sotalol. d,l-Sotalol Implantable Cardioverter-Defibrillator Study Group.
      • Connolly S.J.
      • Dorian P.
      • Roberts R.S.
      • et al.
      Comparison of beta-blockers, amiodarone plus beta-blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: the OPTIC Study: a randomized trial.
      Although at first it might appear contradictory that ablation reduced the risk of several VT-related endpoints, but not recurrent VT/VF, this contradiction is likely explained by the different endpoints reported by the trials, meaning some trials did not contribute data to each endpoint in our analysis. For example, only 3 trials, including fewer than half of the total of 635 patients, contributed to the recurrent VT/VF endpoint. In contrast, 4 of 5 trials, including >95% of the total number of patients, contributed to the appropriate ICD shocks and VT storm endpoints; and all trials contributed to the all-cause mortality endpoint, leading to a higher degree of confidence for these findings. Overlap of events was possible; for example, slow VT underdetection of an ICD could count toward recurrent VT/VF but not toward appropriate ICD therapies.
      The finding that baseline amiodarone therapy was associated with appropriate ICD shocks could indicate that patients receiving amiodarone had more advanced heart disease, as reported in a subgroup analysis of VANISH,
      • Parkash R.
      • Nault I.
      • Rivard L.
      • et al.
      Effect of baseline antiarrhythmic drug on outcomes with ablation in ischemic ventricular tachycardia: a VANISH substudy (Ventricular Tachycardia Ablation Versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease).
      and therefore were at higher risk of receiving ICD shocks. It is also possible that amiodarone was stopped after an acutely successful ablation procedure in some patients, with subsequent recurrence of VT that had been suppressed by amiodarone therapy. However, these interpretations are hypotheses that require confirmation. Of note, only VANISH included a 30-day “blanking” period to allow for full loading of amiodarone
      • Sapp J.L.
      • Wells G.A.
      • Parkash R.
      • et al.
      Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs.
      ; in the other trials, the duration of amiodarone therapy prior to an endpoint was not reported.
      Our results are largely consistent with several other investigations in this field. Three previous meta-analyses did not include the most recently published trials,
      • Mallidi J.
      • Nadkarni G.N.
      • Berger R.D.
      • Calkins H.
      • Nazarian S.
      Meta-analysis of catheter ablation as an adjunct to medical therapy for treatment of ventricular tachycardia in patients with structural heart disease.
      • Patel D.
      • Hasselblad V.
      • Jackson K.P.
      • Pokorney S.D.
      • Daubert J.P.
      • Al-Khatib S.M.
      Catheter ablation for ventricular tachycardia (VT) in patients with ischemic heart disease: a systematic review and a meta-analysis of randomized controlled trials.
      • Maskoun W.
      • Saad M.
      • Abualsuod A.
      • Nairooz R.
      • Miller J.M.
      Outcome of catheter ablation for ventricular tachycardia in patients with ischemic cardiomyopathy: a systematic review and meta-analysis of randomized clinical trials.
      or included studies available only in abstract form.
      • Mallidi J.
      • Nadkarni G.N.
      • Berger R.D.
      • Calkins H.
      • Nazarian S.
      Meta-analysis of catheter ablation as an adjunct to medical therapy for treatment of ventricular tachycardia in patients with structural heart disease.
      One systematic review and meta-analysis has focused on prophylactic CA only (excluding trials in which patients were randomized to AAD).
      • Atti V.
      • Vuddanda V.
      • Turagam M.K.
      • et al.
      Prophylactic catheter ablation of ventricular tachycardia in ischemic cardiomyopathy: a systematic review and meta-analysis of randomized controlled trials.
      However, one of these trials enrolled patients who had received their first ICD shock from a primary prevention ICD after a protocol amendment,
      • Reddy V.Y.
      • Reynolds M.R.
      • Neuzil P.
      • et al.
      Prophylactic catheter ablation for the prevention of defibrillator therapy.
      whereas the other two enrolled patients after a qualifying VT event, and permitted AAD therapy in both arms.
      • Kuck K.H.
      • Tilz R.R.
      • Deneke T.
      • et al.
      Impact of substrate modification by catheter ablation on implantable cardioverter-defibrillator interventions in patients with unstable ventricular arrhythmias and coronary artery disease: results from the multicenter randomized controlled SMS (Substrate Modification Study).
      • Kuck K.H.
      • Schaumann A.
      • Eckardt L.
      • et al.
      Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary artery disease (VTACH): a multicentre randomised controlled trial.
      In practice, the choice between starting or changing AAD therapy on the one hand, vs CA on the other, is often the most relevant decision to be made. This question was addressed by two of the included trials.
      • Sapp J.L.
      • Wells G.A.
      • Parkash R.
      • et al.
      Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs.
      • Al-Khatib S.M.
      • Daubert J.P.
      • Anstrom K.J.
      • et al.
      Catheter ablation for ventricular tachycardia in patients with an implantable cardioverter defibrillator (CALYPSO) pilot trial.
      Due to the small size of one of these trials, a separate meta-analysis of these two was not performed. A recent systematic review and meta-analysis of the effect of AAD and CA in patients with an ICD (including substrates other than IHD) is also available.
      • Santangeli P.
      • Muser D.
      • Maeda S.
      • et al.
      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.
      The current study is the only one to use an expert ERC to systematically review the literature on CA in IHD and perform a meta-analysis.
      Our study has several limitations. The trials included in this analysis mandated the presence of an ICD, or implantation of one soon after randomization. Although this requirement likely improved the sensitivity and uniformity of arrhythmia detection, it limits applicability of our results to patients with an ICD and cannot be extrapolated to those without. Different ablation techniques, technologies, and endpoints were used during the timeframe in which these studies were conducted (Table 2). Causes of death were not uniformly reported across all trials. The absolute number of deaths was small, therefore a separate analysis by cause of death (arrhythmic, cardiac, noncardiac) was not performed. We limited our analysis to trials published as a full peer-reviewed article. The authors are aware of at least 3 other prospective trials that were presented in abstract form, and other studies that were closed due to low enrollment and remain unpublished. How inclusion of these trials would have affected our results is unknown.
      Table 2Ablation strategy characteristics
      Study

      Year

      N
      Ablation strategy descriptionMapping strategies

      N (%)
      VT induction (Yes/No)EndpointEpicardial approach %Total radiofrequency time (min)Fluoroscopy time (min)
      SMS

      2017

      N = 111
      Catheter ablation was to be performed before ICD implantation. Mapping criteria for ablation in stable VT and the lesion design for substrate modification in cases of noninducible or unstable VT followed standard criteria. Inducibility of the targeted VT was assessed by programmed stimulation using the same protocol as before ablation, stimulation at 2 sites in the right ventricle, with ≤3 extrastimuli at 2 drive cycle lengths.CARTO electroanatomical system
      Biosense Webster, Diamond Bar, CA.
      36 (75%)

      EnSite NavX system

      10 (21%)

      Conventional mapping

      2 (4%)
      YesSuccess: Noninducibility of the clinical tachycardia

      Failure: Lack of adequate endocardial target sites or ineffective lesions despite adequate target sites
      NoNRNR
      VANISH

      2016

      N = 259
      Procedures followed a standardized approach that specifically targeted all inducible VTs. VT induction was with programmed ventricular stimulation from two ventricular sites at two drive cycle lengths with ≤3 extrastimuli, coupled not closer than 180 msec. If clinical VT was not induced, isoproterenol could be administered 0.5–10 mcg/min in a dose adjusted to achieve a 30% increase in baseline heart rate. Hemodynamically tolerated VT was approached with activation and entrainment mapping. Nontolerated VT was mapped with pace mapping and bipolar voltage mapping and linear ablation performed parallel to the scar margin. Very fast or noninducible clinical VT ablated with a pure substrate-based approach was used, targeting late potentials and sites with a long stimulus-QRS.Activation mapping

      92 (41.1%)

      Entrainment mapping

      80 (35.7%)

      Substrate mapping

      197 (87.9%)

      Pace mapping

      168 (75.0%)
      YesNoninducibility; very fast VT (cycle length <300 msec) and polymorphic VTs were not specifically targetedNRCatheter Ablation Group: 38.7 ± 21.9

      Antiarrhythmic Group: 36.8 ± 20.6
      Catheter Ablation Group: 31.5 ± 20.8

      Antiarrhythmic Group: 29.4 ± 35.1
      CALYPSO

      2015

      N = 27
      Although endocardial ablation was the preferred ablation strategy in this trial, epicardial ablation was allowed only if the clinical VT could not be ablated via an endocardial approach. The only ablation catheter that was allowed in this study was the Biosense Webster NaviStar ThermoCool externally irrigated 3.5-mm electrode catheter.
      Diamond Bar, CA.
      The selection of the mapping system and details of methods for identifying reentry circuit sites were left to the discretion of the treating physician within guidelines based on whether the VTs were hemodynamically stable or not.YesSuccess: Achieve noninducibility of clinical or presumptive clinical VT if the clinical or presumptive clinical VT was known and was inducible at the beginning of the procedure

      Other acute procedural endpoints: 1) modification of induced VT cycle length (elimination of all VTs with cycle lengths equal to or longer than the spontaneously documented or targeted VT); 2) noninducibility of any VT
      NR
      Epicardial approach allowed, no percentages reported.
      NRNR
      VTACH

      2010

      N = 110
      Mapping criteria for ablation in stable VT and the lesion design for substrate modification in case of noninducible or unstable VT followed standard criteria.CARTO electroanatomical system
      Biosense Webster, Diamond Bar, CA.


      32 (71.1%)

      EnSite noncontact system
      Abbott Laboratories, Abbott Park, IL.


      11 (24.4%)

      Conventional mapping

      2 (4.4%)
      YesSuccess: Noninducibility of any VT at the end of the procedure

      For patients with noninducible VT, the ablation endpoint was substrate modification, defined as absence of all channels inside the area of interest or ablation with linear lesions based on pace mapping along the infarct scar target sites
      NoNRNR
      SMASH-VT

      2007

      N = 128
      The ablation procedure was performed in sinus rhythm. The procedure was divided into 3 steps: 1) induction of VT; 2) localization of the myocardial infarct; and 3) targeting the “arrhythmogenic portions” of the infarct for catheter ablation. Programmed stimulation was performed using up to triple extrastimuli and rapid pacing from the right ventricular apex, right ventricular outflow tract, or left ventricle. If only VF or polymorphic VT was inducible, stimulation was repeated after first infusing a class I antiarrhythmic drug intravenously (procainamide or ajmaline). Catheter mapping and radiofrequency ablation were performed using either the NaviStar 4-mm tip
      Biosense Webster, Diamond Bar, CA.
      standard or the Thermocool 3.5-mm tip saline-irrigated catheter.
      Biosense Webster, Diamond Bar, CA.
      CARTO electroanatomical system
      Biosense Webster, Diamond Bar, CA.
      was used in all procedures
      YesVT was repeatedly induced until either the same VT morphology was induced, or the patient required multiple shocks to terminate induced rhythms during the procedureNRNRNR
      ICD = implantable cardioverter defibrillator; mm = millimeter; msec = millisecond; N = number; NR = not reported; SMASH-VT = Substrate Mapping and Ablation in Sinus Rhythm to Halt Ventricular Tachycardia; VF = ventricular fibrillation; VT = ventricular tachycardia.
      Biosense Webster, Diamond Bar, CA.
      Abbott Laboratories, Abbott Park, IL.
      Diamond Bar, CA.
      § Epicardial approach allowed, no percentages reported.

      Conclusion

      This systematic review and meta-analysis of 5 RCTs found that patients with IHD who underwent CA for VT experienced decreased odds of appropriate ICD therapies, appropriate ICD shocks, VT storm, and cardiac hospitalization vs those who did not undergo ablation.

      Acknowledgments

      The authors thank Sana M. Al-Khatib, MD, MHS, FHRS, CCDS (Duke University Medical Center, Durham, North Carolina) and John L. Sapp, Jr., MD, FHRS (Queen Elizabeth II Health Sciences Centre, Halifax, Canada) for their assistance in providing additional data.

      Appendix

      Appendix 1Author disclosure table
      Committee memberEmploymentHonoraria/Speaking/ConsultingSpeakers’ bureauResearch
      Research and fellowship support are classed as programmatic support. Sources of programmatic support are disclosed but are not regarded as a relevant relationship with industry for writing group members or reviewers.
      Fellowship support
      Research and fellowship support are classed as programmatic support. Sources of programmatic support are disclosed but are not regarded as a relevant relationship with industry for writing group members or reviewers.
      Ownership/Partnership/Principal/Majority stockholderStock or stock optionsIntellectual property/RoyaltiesOther
      Brandon K. Martinez, PharmDUniversity of Connecticut School of Pharmacy, Storrs, Connecticut; Hartford Hospital Evidence-Based Practice Center, Hartford, ConnecticutNoneNoneNoneNoneNoneNoneNoneNone
      William L. Baker, PharmDUniversity of Connecticut School of Pharmacy, Storrs, Connecticut; Hartford Hospital Evidence-Based Practice Center, Hartford, ConnecticutNoneNoneNoneNoneNoneNoneNoneNone
      Anna Konopka, PharmDUniversity of Connecticut School of Pharmacy, Storrs, ConnecticutNoneNoneNoneNoneNoneNoneNoneNone
      Devon Giannelli, PharmDUniversity of Connecticut School of Pharmacy, Storrs, ConnecticutNoneNoneNoneNoneNoneNoneNoneNone
      Craig I. Coleman, PharmDUniversity of Connecticut School of Pharmacy, Storrs, Connecticut; Hartford Hospital Evidence-Based Practice Center, Hartford, ConnecticutNoneNoneNoneNoneNoneNoneNoneNone
      Jeffrey Kluger, MDHartford HealthCare Heart and Vascular Institute, Hartford Hospital, Hartford, Connecticut; University of Connecticut School of Medicine, Farmington, ConnecticutNoneNoneNoneNoneNoneNoneNoneNone
      Edmond M. Cronin, MB, BCh, BAO, FHRS, CCDS, CEPS-AHartford HealthCare Heart and Vascular Institute, Hartford Hospital, Hartford, Connecticut; University of Connecticut School of Medicine, Farmington, ConnecticutNoneNoneNoneNoneNoneNoneNoneNone
      Number value: 0 = $0; 1 = ≤ $10,000; 2 = > $10,000 to ≤ $25,000; 3 = > $25,000 to ≤ $50,000; 4 = > $50,000 to ≤ $100,000; 5 = > $100,000.
      Research and fellowship support are classed as programmatic support. Sources of programmatic support are disclosed but are not regarded as a relevant relationship with industry for writing group members or reviewers.
      Appendix 2Reviewer disclosure table
      Peer reviewerEmploymentHonoraria/Speaking/ConsultingSpeakers’ bureauResearch
      Research and fellowship support are classed as programmatic support. Sources of programmatic support are disclosed but are not regarded as a relevant relationship with industry for writing group members or reviewers.
      Fellowship support
      Research and fellowship support are classed as programmatic support. Sources of programmatic support are disclosed but are not regarded as a relevant relationship with industry for writing group members or reviewers.
      Ownership/Partnership/Principal/Majority stockholderStock or stock optionsIntellectual property/RoyaltiesOther
      Samuel J. Asirvatham, MD, FHRSMayo Clinic College of Medicine, Rochester, Minnesota1: Abbott; 1: BIOTRONIK; 1: Boston Scientific; 1: MedtronicNoneNoneNoneNoneNone1: AliveCorNone
      Sabine Ernst, MD, PhDRoyal Brompton and Harefield Hospitals, London, England2: Biosense Webster; 2: StereotaxisNone3: Catheter Precision; 4: Baylis; 4: Spectrum DynamicsNoneNoneNoneNoneNone
      Number value: 0 = $0; 1 = ≤ $10,000; 2 = > $10,000 to ≤ $25,000; 3 = > $25,000 to ≤ $50,000; 4 = > $50,000 to ≤ $100,000; 5 = > $100,000.
      Research and fellowship support are classed as programmatic support. Sources of programmatic support are disclosed but are not regarded as a relevant relationship with industry for writing group members or reviewers.

      References

        • Tracy C.M.
        • Epstein A.E.
        • Darbar D.
        • et al.
        2012 ACCF/AHA/HRS focused update of the 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
        Heart Rhythm. 2012; 9: 1737-1753
        • Pedersen C.T.
        • Kay G.N.
        • Kalman J.
        • et al.
        EHRA/HRS/APHRS expert consensus on ventricular arrhythmias.
        Heart Rhythm. 2014; 11: e166-e196
        • Al-Khatib S.M.
        • Stevenson W.G.
        • Ackerman M.J.
        • et al.
        2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.
        Heart Rhythm. 2018; 15: e73-e189
        • Schron E.B.
        • Exner D.V.
        • Yao Q.
        • et al.
        Quality of life in the antiarrhythmics versus implantable defibrillators trial: impact of therapy and influence of adverse symptoms and defibrillator shocks.
        Circulation. 2002; 105: 589-594
        • Irvine J.
        • Dorian P.
        • Baker B.
        • et al.
        Quality of life in the Canadian Implantable Defibrillator Study (CIDS).
        Am Heart J. 2002; 144: 282-289
        • Kamphuis H.C.
        • de Leeuw J.R.
        • Derksen R.
        • Hauer R.N.
        • Winnubst J.A.
        Implantable cardioverter defibrillator recipients: quality of life in recipients with and without ICD shock delivery: a prospective study.
        Europace. 2003; 5: 381-389
        • Passman R.
        • Subacius H.
        • Ruo B.
        • et al.
        Implantable cardioverter defibrillators and quality of life: results from the Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation study.
        Arch Intern Med. 2007; 167: 2226-2232
        • Poole J.E.
        • Johnson G.W.
        • Hellkamp A.S.
        • et al.
        Prognostic importance of defibrillator shocks in patients with heart failure.
        N Engl J Med. 2008; 359: 1009-1017
        • Moss A.J.
        • Greenberg H.
        • Case R.B.
        • et al.
        Long-term clinical course of patients after termination of ventricular tachyarrhythmia by an implanted defibrillator.
        Circulation. 2004; 110: 3760-3765
        • Aliot E.M.
        • Stevenson W.G.
        • Almendral-Garrote J.M.
        • et al.
        EHRA/HRS Expert consensus on catheter ablation of ventricular arrhythmias: developed in a partnership with the European Heart Rhythm Association (EHRA), a Registered Branch of the European Society of Cardiology (ESC), and the Heart Rhythm Society (HRS); in collaboration with the American College of Cardiology (ACC) and the American Heart Association (AHA).
        Heart Rhythm. 2009; 6: 886-933
        • Moher D.
        • Liberati A.
        • Tetzlaff J.
        • Altman D.G.
        • PRISMA Group
        Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
        Ann Intern Med. 2009; 151: 264-269
        • Institute of Medicine (US)
        Committee on Standards for Systematic Reviews of Comparative Effectiveness Research. Finding what works in health care: standards for systematic reviews.
        National Academies Press, Washington, DC2011
        • Higgins J.P.
        • Altman D.G.
        • Gøtzsche P.C.
        • et al.
        The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials.
        BMJ. 2011; 343: d5928
        • Higgins J.P.
        • Thomas S.G.
        • Deeks J.J.
        • Altman D.G.
        Measuring inconsistency in meta-analyses.
        BMJ. 2003; 327: 557-560
        • Baker W.L.
        • White C.M.
        • Cappelleri J.C.
        • Kluger J.
        • Coleman C.I.
        • Health Outcomes, Policy, and Economics (HOPE) Collaborative Group
        Understanding heterogeneity in meta-analysis: the role of meta-regression.
        Int J Clin Pract. 2009; 63: 1426-1434
        • Kuck K.H.
        • Tilz R.R.
        • Deneke T.
        • et al.
        Impact of substrate modification by catheter ablation on implantable cardioverter-defibrillator interventions in patients with unstable ventricular arrhythmias and coronary artery disease: results from the multicenter randomized controlled SMS (Substrate Modification Study).
        Circ Arrhythm Electrophysiol. 2017; 10: e004422
        • Sapp J.L.
        • Wells G.A.
        • Parkash R.
        • et al.
        Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs.
        N Engl J Med. 2016; 375: 111-121
        • Al-Khatib S.M.
        • Daubert J.P.
        • Anstrom K.J.
        • et al.
        Catheter ablation for ventricular tachycardia in patients with an implantable cardioverter defibrillator (CALYPSO) pilot trial.
        J Cardiovasc Electrophysiol. 2015; 26: 151-157
        • Kuck K.H.
        • Schaumann A.
        • Eckardt L.
        • et al.
        Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary artery disease (VTACH): a multicentre randomised controlled trial.
        Lancet. 2010; 375: 31-40
        • Reddy V.Y.
        • Reynolds M.R.
        • Neuzil P.
        • et al.
        Prophylactic catheter ablation for the prevention of defibrillator therapy.
        N Engl J Med. 2007; 357: 2657-2665
        • Pacifico A.
        • Hohnloser S.H.
        • Williams J.H.
        • et al.
        Prevention of implantable-defibrillator shocks by treatment with sotalol. d,l-Sotalol Implantable Cardioverter-Defibrillator Study Group.
        N Engl J Med. 1999; 340: 1855-1862
        • Connolly S.J.
        • Dorian P.
        • Roberts R.S.
        • et al.
        Comparison of beta-blockers, amiodarone plus beta-blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: the OPTIC Study: a randomized trial.
        JAMA. 2006; 295: 165-171
        • Parkash R.
        • Nault I.
        • Rivard L.
        • et al.
        Effect of baseline antiarrhythmic drug on outcomes with ablation in ischemic ventricular tachycardia: a VANISH substudy (Ventricular Tachycardia Ablation Versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease).
        Circ Arrhythm Electrophysiol. 2018; 11: e005663
        • Mallidi J.
        • Nadkarni G.N.
        • Berger R.D.
        • Calkins H.
        • Nazarian S.
        Meta-analysis of catheter ablation as an adjunct to medical therapy for treatment of ventricular tachycardia in patients with structural heart disease.
        Heart Rhythm. 2011; 8: 503-510
        • Patel D.
        • Hasselblad V.
        • Jackson K.P.
        • Pokorney S.D.
        • Daubert J.P.
        • Al-Khatib S.M.
        Catheter ablation for ventricular tachycardia (VT) in patients with ischemic heart disease: a systematic review and a meta-analysis of randomized controlled trials.
        J Interv Card Electrophysiol. 2016; 45: 111-117
        • Maskoun W.
        • Saad M.
        • Abualsuod A.
        • Nairooz R.
        • Miller J.M.
        Outcome of catheter ablation for ventricular tachycardia in patients with ischemic cardiomyopathy: a systematic review and meta-analysis of randomized clinical trials.
        Int J Cardiol. 2018; 267: 107-113
        • Atti V.
        • Vuddanda V.
        • Turagam M.K.
        • et al.
        Prophylactic catheter ablation of ventricular tachycardia in ischemic cardiomyopathy: a systematic review and meta-analysis of randomized controlled trials.
        J Interv Card Electrophysiol. 2018; 21: 207-215
        • Santangeli P.
        • Muser D.
        • Maeda S.
        • et al.
        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: 1552-1559