Can Early Ablation of Ventricular Tachycardia Improve Survival?

HomeCirculationVol. 145, No. 25Can Early Ablation of Ventricular Tachycardia Improve Survival? Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBCan Early Ablation of Ventricular Tachycardia Improve Survival? Arvindh N. Kanagasundram, MD, Travis D. Richardson, MD and William G. Stevenson, MD Arvindh N. KanagasundramArvindh N. Kanagasundram https://orcid.org/0000-0001-8295-1528 Cardiovascular Division, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. Search for more papers by this author , Travis D. RichardsonTravis D. Richardson https://orcid.org/0000-0002-9772-0308 Cardiovascular Division, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. Search for more papers by this author and William G. StevensonWilliam G. Stevenson Correspondence to: William G. Stevenson, MD, 1215 21st Avenue South, MCE 5th Floor South Tower, Nashville, TN 37232. Email E-mail Address: [email protected] Cardiovascular Division, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. Search for more papers by this author Originally published21 Jun 2022https://doi.org/10.1161/CIRCULATIONAHA.122.059730Circulation. 2022;145:1850–1852This article is a commentary on the followingDoes Timing of Ventricular Tachycardia Ablation Affect Prognosis in Patients With an Implantable Cardioverter Defibrillator? Results From the Multicenter Randomized PARTITA TrialFirst-Line Catheter Ablation of Monomorphic Ventricular Tachycardia in Cardiomyopathy Concurrent With Defibrillator Implantation: The PAUSE-SCD Randomized TrialIs my patient likely to benefit from this therapy? Clinical trials provide the most reliable answer to this question. Therapies shown to be beneficial in a circumscribed selection of subjects may then applied to the larger population, including the patient in question. Selection biases can reduce the similarities between trial subjects and the larger population, limiting generalizability. We first ask, does our patient meet the study entry criteria? Even among enrolled subjects, there are heterogeneities of baseline profiles and of treatment effect. In every positive study, some patients receive substantial treatment benefit, some receive no benefit, and some are harmed. We would also seek to determine whether our patient fits into any subgroup that is particularly likely or unlikely to benefit, but the size of subgroups rarely allows demonstration of significant interaction. Other considerations relate to the relationship between the treatment and the observed outcome differences. A treatment effect that is biologically plausible strengthens the assertion of benefit. Its absence may suggest new hypotheses, unseen factors at play, or the play of chance.Articles, see p 1829 and p 1839In this issue of the journal, 2 important randomized trials address the role of catheter ablation for preventing sustained monomorphic ventricular tachycardia (VT) in patients with structural heart disease.1,2Sustained monomorphic VT is a serious complication of previous myocardial infarction and cardiomyopathies, often causing sudden death or syncope. Implanted defibrillators (ICDs) provide an effective safety net, terminating episodes of VT. Infrequent VT episodes that are terminated by antitachycardia pacing are often well tolerated, and no additional therapy may be needed. Patients with symptomatic episodes, particularly those requiring ICD shocks, can develop posttraumatic stress disorder, and therapy to prevent recurrences with antiarrhythmic drugs or catheter ablation is desirable.3In addition, the occurrence of VT, and particularly ICD shocks for VT, predict subsequent heart failure hospitalizations and death.4 Several factors may contribute to this association. First, VT is more often associated with large ventricular scars and thus is associated with severe disease. Second, episodes of VT themselves may further impair cardiac function. Third, therapies instituted to prevent VT may have adverse effects including pulmonary or hepatic toxicities of amiodarone,5 proarrhythmia, and bradyarrhythmias, which may increase the need for pacing, potentially aggravating ventricular dysfunction. On the other hand, catheter ablation has procedural risks and the potential for myocardial damage, although procedural mortality is <1%.5–9 Patients who remain free of VT after catheter ablation have a lower mortality than those who have recurrent VT.6 Hence, it is biologically plausible that preventing VT with catheter ablation could reduce heart failure and improve survival if benefits outweigh periprocedural risk.Although the technology has improved, catheter ablation for VT has largely remained a therapy of near last resort when antiarrhythmic drugs fail. This approach is supported by the VANISH trial (Ventricular Tachycardia Ablation Versus Escalated Antiarrhythmic Drug Therapy in Ischemic Heart Disease), which showed that for patients with previous infarction and recurrent VT despite antiarrhythmic drug therapy, catheter ablation improved the composite outcome of death, VT storm, or ICD shocks for VT compared with escalating antiarrhythmic drug therapy.5 Benefit was driven largely by reductions in VT with no difference in total mortality (~27% in both groups during a 2.3-year median follow-up).Recurrent VT despite drug therapy defines a group with relatively severe disease, for which it is reasonable to hypothesize that earlier VT ablation may improve mortality and hospitalizations. Previous trials of catheter ablation for VT in patients with ischemic disease who have not failed antiarrhythmic therapy have generally shown that ablation reduces VT episodes and ICD shocks, but have not had sufficient power to assess the effect on mortality.7–10 A recent trial stopped for futility observed numerically more heart failure hospitalizations and deaths in an early ablation versus deferred ablation group, raising concern that procedural adverse effects may offset benefit.9The 2 trials in this issue of the journal assessed the effect of early catheter ablation and included patients with nonischemic cardiomyopathies in addition to those with coronary artery disease.PARTITAThe PARTITA trial1 assessed the effect of VT ablation on the composite end point of total mortality or hospitalization for worsening heart failure in patients who had not failed antiarrhythmic drug therapy. A landmark feature of this trial is a period of prospective follow-up after ICD implantation, providing clarity and reducing enrollment bias for the randomized phase. Patients receiving an ICD for secondary prevention after VT or primary prevention because of high-risk criteria were enrolled in phase A and followed until their first shock for VT, at which point they were consented for randomization (phase B) to early catheter ablation (within 2 months of ICD shock) versus continuation of standard therapy. Of 517 patients enrolled in phase A, 47.6% had VT episodes during a median follow-up of 2.4 years. However, only 10% of patients received an ICD shock, because most episodes terminated spontaneously or with antitachycardia pacing. This low rate of ICD shocks supports a favorable effect of modern device programming and suggests that waiting for VT to recur before instituting antiarrhythmic drug therapy or performing catheter ablation remains a reasonable strategy for many patients after their first episode of VT.Although only 47 patients were randomized, 23 to ablation and 24 to continuing standard therapy, the trial was stopped when the first interim analysis found that the primary end point had occurred in 1 patient in the ablation group compared with 10 in the standard therapy group (hazard ratio, 0.11 [95% CI, 0.01–0.85]; P = 0.034). There were no deaths in the ablation group versus 8 in the standard therapy group. This difference is striking, but the number of events is very small, leading us to seek reassurance by considering biological plausibility. VT ablation markedly reduced ICD shocks for recurrent VT (8.7% versus 41.7%, P = 0.39), and there was a trend toward reduction in total recurrent VT episodes (30.4% versus 50%). Could this reduction in arrhythmic events translate to a reduction in mortality? Of the 8 deaths, only 3 were attributed to cardiac causes (2 from worsening heart failure and 1 fatal cardiac arrest), 3 were noncardiac (1 sepsis and 2 cancer), and 2 were of unknown cause. Thus, the mechanism by which ablation could have translated to a mortality benefit is not clear.PAUSE-SCDThe PAUSE-SCD trial2 aimed to determine whether catheter ablation would reduce the composite end point of VT recurrence, cardiovascular hospitalization, or death in patients receiving an ICD after an episode of spontaneous or inducible VT. They randomized 133 patients to ablation versus standard care. Ablation was performed within a median of 2 days before ICD implantation. During a median of 31 months, the primary outcome was reduced in the ablation group to 45% versus 59% in the control group (hazard ratio, 0.58 [95% CI, 0.35–0.96]; P = 0.035). The difference was driven by a reduction in VT recurrence (31.7% versus 50.8%; hazard ratio, 0.51 [95% CI, 0.29–0.90]). In striking contrast with the smaller PARTITA trial, there were no meaningful differences in deaths (8.3% versus 6.6%) or in cardiovascular hospitalizations (28.3% versus 32.8%). Patients were not all drug-naïve; ~40% were receiving antiarrhythmic drugs, largely amiodarone, at baseline; and both groups could continue to receive antiarrhythmic drugs during follow-up.These 2 trials showed that catheter ablation soon after ICD implant or after an ICD shock reduced VT recurrences, but the effect on mortality is less certain. Although mortality was a component of the composite end points, the number of events is small, there was 1 more death in the ablation group than the control group in PAUSE-SCD, and the link between ablation and survival in PARTITA is uncertain.Excellent procedural safety in expert centers undoubtedly contributed to the favorable outcomes. There were no procedure-related deaths in either trial, no major procedure complications in the PARTITA trial, and 8.3% complications in PAUSE-SCD. Adverse events are likely to be more common outside the trial setting.These trials are among the first to address early VT ablation in both ischemic heart disease and nonischemic cardiomyopathy (NICM). In NICM, ablation procedures are often more difficult and recurrences more likely.6,11 In contrast with the subendocardial substrate generally observed in ischemic heart disease, the scars that give rise to VT in NICM are varied in location and often intramural or subepicardial. Epicardial ablation by accessing the pericardial space is more often required in this population and has been associated with a 5 to 12% risk of major complications, usually pericardial bleeding.12 In PARTITA, 22% of patients had nonischemic dilated cardiomyopathy, and the majority had ischemic heart disease. Although epicardial ablation was allowed, none was performed. PAUSE-SCD was conducted in Asia; the minority of patients, 34.7%, had ischemic heart disease; 30.6% had NICM, and 34.7% had arrhythmogenic right ventricular cardiomyopathy. It is notable that subgroup analysis of the primary end point showed better outcome with ablation in patients with arrhythmogenic right ventricular cardiomyopathy, and ischemic heart disease (not statistically significant), but for patients with NICM, the trend was for worse outcome with ablation (64.7% versus 50.%; Figure 3 in the PAUSE-SCD supplement). Although patients with NICM met the inclusion criteria for these trials, further study is warranted to determine the effect of early ablation in this important subgroup.In summary, after an initial episode of sustained VT that warrants ICD implantation, programming should be optimized to minimize the chance of ICD shocks. When VT recurs, particularly with ICD shocks, it is reasonable to consider catheter ablation at that time to prevent further VT, particularly for patients with ischemic heart disease or arrhythmogenic right ventricular cardiomyopathy. More studies are needed to clarify whether reducing VT with catheter ablation reduces hospitalizations and improves survival.Article InformationSources of FundingNone.Disclosures The authors report the following: W.G.S.: speaking honoria from Boston Scientific, Medtronic, Biotronik, Johnson and Johnson, and Abbott, patent for needle ablation consigned to Brigham Hospital; T.D.R.: consulting fees from Johnson and Johnson and Philips, research funding from Medtronic and Abbott; and A.N.K., speaking honoraria from Johnson and Johnson.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Circulation is available at www.ahajournals.org/journal/circFor Sources of Funding and Disclosures, see page 1852.Correspondence to: William G. Stevenson, MD, 1215 21st Avenue South, MCE 5th Floor South Tower, Nashville, TN 37232. Email william.g.[email protected]orgReferences1. Della Bella P, Baratto F, Vergara P, Bertocchi P, Santamaria M, Notarstefano P, Calo L, Orsida D, Tomasi L, Piacenti M, et al. Does timing of ventricular tachycardia ablation affect prognosis in patients with an implantable cardioverter defibrillator? Results from the multicenter randomized PARTITA trial.Circulation. 2022;145:1829–1838. doi: 10.1161/CIRCULATIONAHA.122.059598LinkGoogle Scholar2. Tung R, Xue Y, Chen M, Jiang C, Shatz DY, Besser SA, Hu H, Chung F-P, Nakahara S, Kim YH, Satomi K. First-line catheter ablation of monomorphic ventricular tachycardia in cardiomyopathy concurrent with defibrillator implantation: the PAUSE-SCD randomized trial.Circulation. 2022;145:1839–1849. doi: 10.1161/CIRCULATIONAHA.122.060039LinkGoogle Scholar3. 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Epicardial access for VT ablation: analysis of two different puncture techniques, incidence of adhesions and complication management.Clin Res Cardiol. 2021; 110:810–821. doi: 10.1007/s00392-020-01711-zCrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesDoes Timing of Ventricular Tachycardia Ablation Affect Prognosis in Patients With an Implantable Cardioverter Defibrillator? Results From the Multicenter Randomized PARTITA TrialPaolo Della Bella, et al. Circulation. 2022;145:1829-1838First-Line Catheter Ablation of Monomorphic Ventricular Tachycardia in Cardiomyopathy Concurrent With Defibrillator Implantation: The PAUSE-SCD Randomized TrialRoderick Tung, et al. Circulation. 2022;145:1839-1849 June 21, 2022Vol 145, Issue 25 Advertisement Article InformationMetrics © 2022 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.122.059730PMID: 35728052 Originally publishedJune 21, 2022 Keywordsventricular tachycardiaEditorialscardiomyopathyradiofrequency catheter ablationPDF download Advertisement SubjectsArrhythmiasCatheter Ablation and Implantable Cardioverter-DefibrillatorElectrophysiology