Part II: Catheter Ablation of Ventricular Tachycardia Late After Myocardial Infarction: Techniques, Indications, and Recent Advances

The initial clinical series of catheter ablation for VT limited patient enrollment to those with a single or dominant hemodynamically stable and reproducible VT morphology. However, patients with stable monomorphic VT represent only a minority of those with clinically significant VT. For example, Morady et al. reported in their original series that only 10% of consecutive patients with coronary heart disease (CHD) and refractory VT met criteria of having hemodynamically stable or mappable VT.²⁸ Another early series suggested that only 16% of 307 patients referred for treatment of refractory VT met enrollment criteria, which included hemodynamically tolerated and sustained monomorphic VT reproducible by programmed stimulation.²⁹ Furthermore, only about 60% of patients in this study could tolerate VT sufficiently for mapping and ablation at the time of procedure. Accordingly, advances in catheter mapping techniques would be required if catheter ablation was to benefit the majority of patients presenting with drug refractory VT. More recently, standard mapping techniques have been applied to target VT in patients with multiple VT morphologies in an effort to broaden patient eligibility. In 1998, Stevenson et al. reported on catheter ablation in 52 post-MI patients who were selected for ablation without regard to the presence of multiple VT morphologies. On average, there were 3.9 ± 2 VT morphologies per patient and all mappable VTs were targeted. This patient population was more representative of those with VT after myocardial infarction. Only 67% of patients demonstrated stable and mappable VT morphologies without associated unstable VT, and one-third of patients required more than one ablation session. Significant complications occurred in 10% of patients, and 33% had recurrent VT over a 3-year period.³⁸ These results underscore the difficulty in approaching pleomorphic and unstable VT in post-MI patients using standard mapping and ablation techniques. The only multi-center study of catheter ablation for VT was published in June 2000. Enrollment was offered to patients with ischemic heart disease who demonstrated drug refractory hemodynamically stable VT, frequent recurrences, and an ICD in situ.³⁹ Patients were enrolled without regard to the presence of multiple VT morphologies. The investigational protocol dictated that all hemodynamically tolerated VTs be targeted. This trial employed a new actively cooled ablation catheter (Cardiac Pathways, Sunnyvale, California), which is thought to increase power delivery and lesion size during catheter ablation.⁴⁰ One hundred and seventy-one procedures were performed on 146 patients, with 11 of the second procedures done for arrhythmia recurrence. Acute suppression of all hemodynamically stable VT morphologies was reported in 75% of subjects; however, 59% of subjects demonstrated either inducible unstable and unmappable VT morphologies or failure to achieve the endpoint of ablating all mappable VT morphologies. Arrhythmia recurrence was 46% during 243 ± 153 days of follow-up. Major complications occurred in 8%. The results of single-center series were confirmed regarding overall efficacy of the procedure. The trial also confirmed the limitations of standard mapping techniques which are ineffective for treatment of unstable pleomorphic VT; 40% of individuals enrolled in this trial had inducible VT with cycle lengths shorter than 300 ms and these VT morphologies were not targeted. Further studies will be required to determine whether successful targeting of rapid VT morphologies improves long-term success. This trial validated the concept that targeting multiple VT morphologies is feasible, thus expanding eligibility to individuals with pleomorphic and/or unstable VT, so long as some VT morphologies were mappable. New Catheter Ablation Strategies for Refractory Post Infarction Ventricular Tachycardia The suggestion that there may be clinical benefit to increasing radiofrequency ablation lesion size using actively cooled catheters led to further investigation using an irrigated-tip catheter system (Thermo-Cool^TM, Cordis-Webster, Baldwin Park, California). This is an open system using saline infusion through the catheter to cool the catheter tip and enhance RF power delivery during ablation. Power delivery is often limited by the catheter-tissue interface temperature, because excessive tip temperature produces charring and limits ablative current flow to adjacent tissue. The irrigated tip system produced lesions in humans of up to 7 mm after endocardial energy application in vivo.⁴¹ In animal studies, this system produced lesions of 4-8 mm depth, and was not found to be associated with thrombus formation⁴² in distinction to standard RF catheter systems. The later finding may be of significance, since stroke is an important complication of catheter ablation for VT after MI and has been reported to occur in 2.8% of individuals when standard mapping and ablation techniques were used.⁴³ Further studies will be required to define the stroke rate using new ablation systems. Improved efficacy of the irrigated catheter system as compared with a standard ablation system was suggested by observations that the irrigated-tip catheter was better able to terminate VT at tachycardia isthmus sites, was able to deliver more power during ablation, resulted in quicker tachycardia termination during ablation, and required fewer RF energy applications to achieve the procedural endpoint of acute VT suppression.⁴⁴ Arrhythmia recurrence rates were also reported to be less with the irrigated catheter system though the difference did not reach significance.⁴⁴ Catheter-based tissue freezing is also under development as a percutaneous catheter ablation system.⁴⁵ Initial studies suggest that this technology is effective for catheter ablation of supraventricular tachycardias,^46,47 is less likely than RF ablation to produce patient discomfort,⁴⁸ and is less likely to produce thrombus in vivo than RF energy.⁴⁹ Data are not yet available regarding the use of percutaneous catheter based cryoablation for ventricular tachycardia, although the established success of endocardial surgical cryoablation suggests that further investigation is warranted. 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Table 1. Mapping criteria for identification of target sites for catheter ablation of VT. Standard Mapping Fragmented DP recorded during VT Stim-QRS interval during pacing = DP-QRS interval during VT Pre-systolic DP timed Anatomic Mapping Site is within area of low voltage endocardial scar Isolated DP recorded during SR or VT Site is bounded by electrically unexcitable tissue Long Stim-QRS delay evident during pacing Pace map matches VT QRS morphology Abbreviations: DP = low amplitude fragmented diastolic potential recorded from mapping catheter; SR = sinus rhythm; VT = Ventricular Tachycardia; QRS = surface ECG representation of ventricular activation; Stim = Pacing stimulus artifact on ECG recording; CL = cycle length of tachycardia in milliseconds; PPI = Post-pacing interval or the interval recorded by the distal mapping catheter electrodes between the pacing stimulus artifact and the first local activation during tachycardia after pacing from the mapping catheter with entrainment of the tachycardia⁵ Table2. Patient selection for catheter ablation of VT late after myocardial infarction. Standard Mapping Hemodynamically Stable VT Single or Few Dominant VT Morphologies Failed Antiarrhythmic Drug Therapy Anatomic Mapping Hemodynamically Stable or Unstable VT Single or Multiple VT Morphologies Failed Antiarrhythmic Drug Therapy Standard Mapping refers to ablation guided by mapping via endocardial electrogram recording and pacing maneuvers during stable VT to identify target sites for ablation. Criteria for targeting catheter ablation have been previously described,⁵ see Figure 1 legend. Not all criteria must be met for identification of successful ablation sites. Anatomic Mapping refers to ablation guided by mapping, predominantly during sinus rhythm, using an advanced mapping system to render a 3-D representation of the ventricular endocardial morphology and extent of post-infarct scar. Ablation targets are identified by information about the distribution of low voltage endocardial recordings (34 together with data about myocardial activation in response to pacing from the mapping catheter or during brief episodes of induced VT. Not all criteria must be met for identification of successful ablation sites. Table3. Guidelines of catheter ablation of ventricular tachycardia.¹ Ablation recommended for: Patients with symptomatic sustained monomorphic VT when the tachycardia is drug resistant the patient is drug intolerant or does not desire long-term drug therapy Patients with sustained monomorphic VT and an ICD who are receiving multiple shocks not manageable by reprogramming or concomitant drug therapy Ablation can be considered for: Nonsustained VT that is symptomatic when the tachycardia is drug resistant or the patient is drug intolerant or does not desire long-term drug therapy Ablation is NOT indicated for: Patients with VT that is responsive to drug, ICD, or surgical therapy and that therapy is well tolerated and preferred by the patient to ablation Unstable, rapid, multiple, or polymorphic VT that cannot be adequately localized by current mapping techniques Asymptomatic and clinically benign nonsustained VT

Of greater significance has been development of advanced catheter mapping system that have demonstrated utility in ablation of unstable or hemodynamically untolerated VT.^34,50 These system permit sinus rhythm mapping of VT using new mapping criteria,³⁴ or mapping of VT during very brief episodes of arrhythmia which are uniformly tolerated.50 The CARTO^TM electro-anatomic mapping system (Biosense Webster, Inc., Diamond Bar, California)^51,52 has been used by the majority of groups reporting recent experience with catheter ablation for unstable VT late after MI. This system allows tracking of catheter tip position in three-dimensional space. Magnetic field sensors in the catheter tip measure the strength of low-frequency magnetic fields created by 3 electromagnets positioned under the patient. A software algorithm processes this information to calculate catheter tip position relative to a reference electrode. Information about endocardial electrograms, including the waveform morphology, the local electrogram amplitude, and the local activation timing relative to an intracardiac reference signal, are recorded by the system together with the catheter tip position.⁵¹ These data are then presented on a computer-generated three-dimensional rendering of the endocardial surface of the heart that can be annotated by the user. Local activation or endocardial electrogram voltage amplitude data are associated with each acquired point and are presented on an anatomically accurate rendering of the cardiac chamber with a user-adjustable color scale (Figure 2B). In practice, ablative radiofrequency energy can be delivered via the catheter.⁵² The system is able to assign catheter tip location with a high degree of reproducibility (0.74 mm ± 0.13 mm) and accuracy (0.73 mm ± 0.03 mm).⁵¹ Prior studies have demonstrated that areas of endocardial scar late after MI can be identified by a diminished peak to peak voltage and fragmented morphology of the local electrogram.²² Initial animal and human studies with CARTO^TM revealed that the rendered voltage maps could accurately define regions of scar after myocardial infarction (Figure 2).⁵³ The first report of catheter ablation for treatment of unstable VT was made by Marchlinski et al. in 2000.³⁴ An electro-anatomic mapping system was used in sinus rhythm to guide catheter ablation of unstable VT. Sinus rhythm mapping guided ablation by identifying areas of infarct scar. In this report, nine patients with medically refractory rapid and unstable VT late after MI underwent sinus rhythm mapping to identify low amplitude fractionated electrograms from regions of endocardial scars. Pace map matching to brief inductions of VT identified regions of the scar border zone where the VT wave front was exiting to produce VT (Figure 2). Linear lesions using 8-87 RF applications per patient (mean: 55) were made extending from the region of dense scar to the tachycardia exit site. All patients had ICDs in situ with frequent VT episodes in the month prior to the ablation procedure. Seven of the nine patients had compete suppression or significant modification of VT. Furthermore, no patients had documented recurrent VT as determined by ICD interrogation, except one patient with a single shock at 9 months (mean follow-up: 8 m). Thus, 89% of patients that had not previously been candidates for catheter ablation due to multiple unstable VTs had complete suppression of their arrhythmia during the limited follow-up of 3-36 months. In 2001, another group reported on 40 patients undergoing ablation without regard to the presence of VT stability or multiple morphologies.³⁵ In this series, the CARTO system was also used for sinus rhythm mapping during which the infarct scar region was defined, and pace mapping was used to identify tachycardia exit sites. Ablation lines were then created parallel to the scar border and through areas that demonstrated a stim-QRS delay of > 40 ms during pacing with the QRS morphology matching that of VT. Ablation lines were extended for 2-4 cm. Eighty-three percent of patients had suppression or significant modification of VT. In this patient cohort, only 17.5% of patients had exclusively stable and mappable VTs, which underscores the importance of these mapping strategies to expand patient eligibility for catheter ablation. No patients had worsening heart failure. Delivery of multiple RF lesions to the left ventricular (LV) endocardial surface might be expected to compromise LV systolic function; however, the linear ablation strategies employed in these studies targeted only endocardial regions within the infarct scar which were already damaged by prior MI. Careful assessment of LV function after linear ablation guided by electro-anatomic mapping suggested that the production of long lines of RF lesions (26 ± 2 lesions per patient) is safe and does not worsen left ventricular systolic function.⁵⁴ An interesting finding in several studies of catheter ablation for VT was that ablation of a single isthmus region within the infarct scar was occasionally observed to abolished more than one VT morphology. For example, one series employed standard mapping techniques to identify scar isthmuses that were part of the tachycardia circuit and reported that 23 mapped VT morphologies were eliminated by targeting a total of 11 isthmus sites in 9 of 19 subjects.⁵⁵ This finding supported the notion that a single tachycardia isthmus could produce multiple clinical VT morphologies differentiated by the circuit exit site from the scar region (Figure 1). Identification of potential common isthmuses within infarct scar is enhanced by the CARTO electro-anatomic mapping system, which permits clear annotation of endocardial regions within the infarct scar that are electrically unexcitable during high output unipolar pacing (Figure 2).⁵⁶ Using this technique, Soejima et al. identified unexcitable regions in each of the 14 post-MI patients with VT that were studied.⁵⁶ All VT circuits were adjacent to areas of unexcitable tissue. Furthermore, of potential tachycardia isthmuses so identified in these 14 patients, eleven isthmuses in eight patients participated in the genesis of more than one VT morphology. Catheter ablation targeting these 11 isthmuses suppressed 30 distinct VT morphologies. Accordingly, it is feasible to successfully treat individuals with multiple VT morphologies by identifying and targeting critical conducting isthmuses within the infarct scar with catheter ablation. Other groups have also reported similar short-term success using electro-anatomic mapping in sinus rhythm to guide ablation of VT after MI by targeting potential tachycardia isthmus^57,58 or using linear ablation to target the tachycardia exit sites.⁵⁹ It remains to be determined whether overall efficacy of catheter ablation for VT will be enhanced by these techniques though it is already clear that patient eligibility for catheter ablation has been expanded by these new approaches which permit targeting of both hemodynamically stable and unstable arrhythmias. Another advanced mapping system (Ensite, Endocardial Solutions, Inc., St. Paul, Minnesota) has been reported to permit mapping and ablation of unstable ventricular tachycardia late after MI. This system uses a 64-electrode balloon catheter that is positioned within a heart chamber, but which does not need to contact the heart surface in order to record endocardial activation (non-contact mapping). Far-field endocardial electrograms are recorded by the balloon electrodes and are used to compute 3,360 virtual electrograms, which are available for review and can be used to render an isopotential map of a pre-recorded tachycardia cycle sampled every 0.83 ms. A locator system with a resolution to 4 mm is used to define the chamber geometry. Initial reports validated the system,⁶⁰ so long as the balloon electrodes were within 3.4 cm of the chamber wall,^50,60 and demonstrated feasibility of using the system for catheter ablation.⁶¹ Two additional studies, when taken together, reported on 24 patients with post-MI VT.^50,62 The mapping system correctly identified tachycardia exit sites in the majority of patients, diastolic pathways or isthmuses presumed to be within the infarct scar in some patients, and the entire tachycardia circuit only rarely. Successful ablation was noted in 64-79% of patients.^50,62 Unstable VTs were successfully targeted in half of cases.⁵⁰Patient Selection for Catheter Ablation of Refractory VT Late After Myocardial Infarction Current recommendations regarding catheter ablation of ventricular tachycardia late after MI have been published¹ and appear in Table 2. Due to the requirement that mapping and ablation using standard methods be done during sustained tachycardia, these guidelines, developed in 1995, recommended that patients with drug refractory stable, monomorphic, and hemodynamically tolerated ventricular tachycardia were the most ideal candidates for catheter ablation. However, new arrhythmia mapping techniques show promise for treatment of unstable or untolerated VT (Table 3). When VT is recurrent, drug refractory, and unstable or pleomorphic, treatment alternatives could include catheter ablation using advanced mapping techniques, arrhythmia surgery, or cardiac transplantation. Accordingly, consultation and case-specific consideration regarding the availability of advanced treatment options should be considered. Conclusions Ventricular tachycardia after myocardial infarction is caused by re-entry of myocardial activation wave fronts through the post-infarct scar. Isthmuses produced by surviving myocytes within the infarct scar are often located near the endocardial surface and participate in arrhythmogenesis by producing regions of slow conduction, which allow for initiation and maintenance of re-entry. ICDs are the first-line therapy for ventricular tachycardia after MI; however, recurrent symptomatic episodes of VT are common and require treatment. While antiarrhythmic drugs are often used to treat recurrent VT in ICD patients, drug inefficacy or intolerance is common. Percutaneous catheter ablation of VT is well established to treat drug refractory VT. Standard mapping techniques require that the target VT be hemodynamically stable and monomorphic to allow for arrhythmia mapping during sustained episodes of tachycardia. In general, patients with stable monomorphic VT represent a small minority of those who require treatment for drug refractory VT. New electro-anatomical catheter mapping systems and new catheter ablation systems have been developed that may permit multiple pleomorphic and unstable VT morphologies to be successfully targeted with catheter ablation. Arrhythmia mapping with these systems can be accomplished during normal sinus rhythm or during brief and limited episodes of tachycardia to guide catheter ablation of either slow conducting isthmuses within the tachycardia circuit or the tachycardia exit sites. Initial studies suggest excellent long-term arrhythmia suppression with low complication rates. Further studies are required to define the role of these new technologies and mapping strategies for treatment of recurrent ventricular tachycardia late after myocardial infarction.