Inducibility Conundrum for Ablation of Ventricular Tachycardia

HomeCirculation: Arrhythmia and ElectrophysiologyVol. 11, No. 3Inducibility Conundrum for Ablation of Ventricular Tachycardia Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessEditorialPDF/EPUBInducibility Conundrum for Ablation of Ventricular TachycardiaAre We Done Yet? Roy M. John, MBBS, PhD, Arvindh N. Kanagasundram, MD and William G. Stevenson, MD Roy M. JohnRoy M. John From the Cardiovascular Division, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. , Arvindh N. KanagasundramArvindh N. Kanagasundram From the Cardiovascular Division, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. and William G. StevensonWilliam G. Stevenson From the Cardiovascular Division, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN. Originally published15 Mar 2018https://doi.org/10.1161/CIRCEP.118.006246Circulation: Arrhythmia and Electrophysiology. 2018;11:e006246See Article by Oloriz et alThe application of programmed electrical stimulation (PES) by Wellens et al1 to the evaluation of ventricular tachycardia (VT) in humans was a landmark achievement establishing a method that has led to pathophysiologic insights and improved VT diagnosis and therapy for >4 decades. The ability to initiate VT, ablate, and then demonstrate that VT is no longer inducible has been fundamental to assessing the acute effects of catheter ablation. Although there has been substantial progress with ablation in patients with heart disease and scar-related reentry and it is superior to escalating antiarrhythmic drug therapy in many situations, multicenter trials continue to report arrhythmia recurrences in 20% to 50% of patients.2,3 Recurrences are more frequent for nonischemic dilated cardiomyopathies and are associated with increased mortality and hospitalizations.2,4,5 Can PES shed light on the reasons for ablation failure? Or is its use to assess the acute procedural endpoint part of the problem? When one ablates an accessory pathway, the arrhythmia is no longer inducible, but we also confirm that the pathway is gone. Does use of noninducibility as an endpoint obfuscate the goal of abolishing the substrate?There are many limitations and caveats in the use of PES for assessing procedure outcome. VT inducibility is probabilistic and influenced by drugs, autonomic state, and the nuances of the stimulation protocol. The pacing sites, number of extrastimuli, and manner in which the extrastimuli are applied vary among laboratories. Some patients do not have inducible VT at baseline. Initiation of reentrant VT demonstrates that the substrate for reentry is present but is not informative about the existence of initiating triggers. Programmed stimulation is generally performed from sites remote from the reentry circuit, whereas recordings of spontaneous VT initiation often show that the first VT beat is similar to the subsequent beats, suggesting origin close to or from the reentry circuit.Early ablation approaches focused on inducing a VT with the same QRS and cycle length as one that had occurred spontaneously, and defining it as a clinical VT. Identifying the circuit of a clinical VT and rendering that VT no longer inducible by ablation was associated with freedom from spontaneous recurrence of that VT.6 However, PES in patients with scar-related VT usually induces multiple morphologies of VTs. Inducible VTs that differ from the clinical VT have been referred to as nonclinical, implying that they have a lower chance of occurring spontaneously and were considered a manifestation of the limited specificity of PES. However, the presence of inducible nonclinical VTs is associated with VT recurrences.7,8 Complete noninducibility would, therefore, seem to be a reasonable goal. Despite multiple and usually poorly tolerated VTs, this is now feasible with substrate mapping targeting areas of abnormal conduction within low-voltage scar recognized from abnormal sinus rhythm electrograms or pace mapping. Extensive substrate-guided ablation is associated with less recurrent VT compared with ablation that targets only an inducible hemodynamically tolerated VT.9,10The optimal approach to substrate ablation is still under investigation, and there are limitations.11 Although an anatomic approach covering the entire low-voltage region is used by some, it is not an option for nonischemic cardiomyopathy patients who do not have large confluent areas of low-voltage scar, it can be difficult for large scars, it is problematic when the low-voltage area includes high-risk regions near the His bundle or epicardial coronary arteries, it may include areas of electrically inert fibrosis that do not require ablation, and finally, this extent of ablation is clearly not necessary for success in all patients. With more focused substrate ablation, a VT remains inducible in up to 50% of patients, and some of these VTs can be ablated with the guidance of additional mapping.11,12 When substrate ablation is combined with ablation targeting inducible VTs, successful abolition of the substrate electrograms is associated with a lower risk of recurrences.11–14With any of these approaches, it is not always possible to abolish inducible VT, which brings us back to the interpretation of PES. If nonclinical VTs remain inducible should ablation continue, should it proceed to the epicardium, or include high-risk areas? There are no randomized trials comparing these strategies. Stopping the procedure and considering further ablation if VT recurs is often reasonable. A recent study by Watanabe et al7 suggests that better recognition of inducible VTs that confer increased risk is possible. Fast VTs are typically more difficult to initiate with PES than slow VTs, suggesting that they may indicate less risk, but this contention is not consistently supported in retrospective analysis.15 Recently, Watanabe et al proposed defining fast inducible VT as having a cycle length of ≤30 ms+the right ventricular effective refractory period measured at a paced cycle length of 400 ms, reasoning that these VTs may more likely be based on functional electrophysiological properties, rather than structural substrate. After ablation of mappable VT and substrate in 191 patients, 70 had nonclinical VTs inducible. The 3-year VT recurrence rate was 83% for those with a slow VT inducible, whereas those with fast VT inducible had a 37% recurrence rate that was not statistically different from patients without inducible VT (26%).When VTs are no longer inducible, should the ablation procedure be terminated? Addition of substrate ablation seems to reduce recurrences.9–14 Unfortunately, PES immediately after ablation has limited sensitivity for predicting recurrences; and 11% to 37% of patients initially not inducible subsequently recur.7,8 In this issue of the Journal, Oloriz et al16 analyze their experience of PES immediately (early) and late (4–6 days) after ablation for predicting VT recurrence in patients with scar-related VT (48% ischemic). Early and late PES findings were concordant in 67%. However, 26% of patients with no inducible VT early had VT induced at late PES, and these patients had a higher recurrence rate compared with noninducible patients (59% versus 9%). Importantly, half of the VTs induced had been terminated with radiofrequency ablation at the index procedure. The high reinducibility rate was observed even though the stimulation protocol at the end of the ablation procedure was more aggressive, incorporating 4 extrastimuli from multiple sites, as opposed to 3 extrastimuli from only the right ventricular apex (with noninvasive programmed stimulation in 86%) at late PES. The results are consistent with a previous report by Frankel et al,17 who observed that approximately half of the patients with no inducible VT at the end of the ablation procedure had VT inducible 3 to 5 days later, one third of which were previously defined clinical VTs, and that arrhythmia-free survival at 1 year was better for those with no inducible VT compared with those with inducible clinical VT or nonclinical VT (85%, 30%, and 65%, respectively). Frankel et al found that inducible VTs slower than 300 ms were associated with greater risk of recurrence in univariable analysis; Oloriz et al16 found only a trend for association of slower VT with recurrence.17Although there are many factors that could contribute to the poor sensitivity of early PES for identifying recurrence risk, failure to create durable lesions is likely a major contributor. Achieving good radiofrequency lesions, facilitated by adequate electrode tissue contact, radiofrequency power, and duration to achieve lesion depth, is likely important. We and others use lack of pacing capture (eg, at 10 mA) as a sign of adequate ablation, but optimal parameters have not been defined, and it is not always possible to achieve noncapture, particularly in the scar border.18,19There are several limitations to studies of PES. Most are retrospective and observational. A substantial number of patients do not undergo PES because of concerns for hemodynamic impairment, and these patients tend to have more severe disease and worse outcomes.16,17 Changes in antiarrhythmic drug therapy were generally left to the treating physician and could influence inducibility and recurrences. Stimulation protocols and ablation approaches varied.We are not done with programmed stimulation. Initiation of VT provides an opportunity to confirm the diagnosis and obtain the QRS morphology of VTs that are terminated by implantable cardioverter defibrillators, information that we use to help guide ablation. When a clinical VT is known and inducible, abolition of that VT, whether by a substrate-targeted approach or limited mapping in VT, remains an important goal because failure to achieve this end point is associated with the highest risk or recurrence. The addition of substrate-guided ablation confined to low-voltage regions of scar is reasonable. Whether additional ablation for inducible nonclinical VTs with more mapping and larger lesions will improve outcomes is not clear. Many of these patients will not have recurrent VT, particularly if the induced VT is rapid. Repeating PES a few days after ablation can identify patients whose resolving radiofrequency lesions put them at increased risk for VT recurrence and can inform about implantable cardioverter defibrillator programming.16 Whether additional ablation at that time would improve outcomes is not clear; it is possible that procedure risks may be somewhat greater than that at the first procedure. However, given the mortality and morbidity associated with recurrent VT, early repeat ablation is a reasonable consideration for some patients and warrants prospective study.DisclosuresDr Kanagasundram has received speaking honoria from Biosense Webster, Zoll, and Janssen, Inc. Dr John has received honoria from Biosense Webster and Abbott Medical. Dr Stevenson has received speaking honoria from Abbott Medical and Boston Scientific and is coholder of a patent for needle ablation that is consigned to Brigham Hospital and coheld with Biosense Webster.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.Circ Arrhythm Electrophysiol is available at http://circep.ahajournals.org.Correspondence to: William G. Stevenson, MD, Cardiovascular Division, Department of Medicine, Vanderbilt University Medical Center, 1215 21st Ave S, MCE 5th Floor S Tower, Nashville, TN 37232. E-mail [email protected]References1. Wellens HJ, Schuilenburg RM, Durrer D. Electrical stimulation of the heart in patients with ventricular tachycardia.Circulation. 1972; 46:216–226.LinkGoogle Scholar2. 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