Catheter Ablation for Scar-related Ventricular Tachycardias

Catheter Ablation for Scar-related Ventricular Tachycardias Jean-Marc Raymond, MD, Frederic Sacher, MD, Robert Winslow, MD, Usha Tedrow, MD, and William G. Stevenson, MD Abstract: Patients with scar-related ventricular tachycardia (VT) are subject to frequent arrhythmia recurrences; antiarrhythmic drug therapy has been disappointing due to poor efficacy and side effects. Patients receiving multiple implantable cardioverter-defibrillator shocks because of VT have impaired quality of life. The role of catheter ablation in the treatment of ventricular arrhythmias has been increasing in the last 2 decades. As more knowledge is gained about the mechanisms of VT, the potential for doing ablation has increased. Now, multiple VTs and unstable VTs can be targeted by ablation strategies. Also, electroanatomic mapping systems have made substrate mapping feasible. The purpose of this article is to review the selection and preparation of patients who require catheter ablation for scar-related VT, the different mapping techniques, and the ablation strategies employed. An overview of the pathophysiology of scarrelated VT and the variety of heart diseases that are related to scar-related VT is provided. (Curr Probl Cardiol 2009;34: 225-270.) entricular scar from prior myocardial infarction is the most common cause of sustained monomorphic ventricular tachycardia (VT). Arrhythmogenic right ventricular dysplasia, cardiac sarcoidosis, nonischemic cardiomyopathies, and ventricular surgical repairs V Disclosures: William G. Stevenson is a consultant for Biosense Webster and receives Faculty Honoria from Biosense Webster, Boston Scientific, Medtronic, and St Jude Medical. Usha B. Tedrow receives research funding from Medtronic and Boston Scientific. The other authors have no conflicts of interest to disclose. Curr Probl Cardiol 2009;34:225-270. 0146-2806/$ – see front matter doi:10.1016/j.cpcardiol.2009.01.002 Curr Probl Cardiol, May 2009 225 (such as for tetralogy of Fallot) can also produce scarring, leading to VT. Implantable cardioverter-defibrillators (ICDs) have become the mainstay of treatment of this arrhythmia.1 ICDs effectively terminate VT by antitachycardia pacing or shocks, and, often, prevent sudden cardiac death.2,3 ICD shocks are painful and reduce the quality of life.4,5 Treatments that prevent or reduce episodes of VT, therefore, remain important and are needed in 39-70% of patients who have an ICD placed following a spontaneous episode of VT.4,6 Approximately 10% of patients experience an electrical storm, defined as 3 or more episodes of arrhythmia within 24 hours, in the first 2 years following implantation of their devices.6 Moreover, ICDs do not prevent VT. Furthermore, spontaneous episodes of VT are associated with increased mortality, despite effective treatment by the ICD.7 VT ablation has been proven to decrease the number of shocks in high-risk patients with ICDs.8 It can be lifesaving when VT is incessant. However, VT ablation is a procedure that remains technically challenging with a success rate lower than for ablation of common supraventricular tachycardias. This review provides an assessment of the risks, benefits, and methods of VT ablation for patients with scar-related VTs resulting from different disease states. The substrate and mechanism of scar-related VT, mapping techniques, and ablation techniques of scar-related VT is discussed, as are patient selection and preparation, technological innovations, outcomes, and complications. Indication and Patient Selection The American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden death give ablation a Class I (level of evidence C) recommendation as adjunctive therapy for patients with an ICD who are receiving multiple shocks due to sustained VT, not amenable to ICD reprogramming or drug therapy.9 If the patient and physician wish to avoid long-term drug therapy, ablation can also be performed (Class I).9 In general, ablation for scar-related VT is usually considered for patients with recurrent symptomatic monomorphic VT, often with frequent ICD shocks or incessant VT. In some cases reduction or withdrawal of an antiarrhythmic medication because of side effects results in the need for catheter ablation. Ablation is not generally considered an option for polymorphic VT, unless storms of this arrhythmia and frequent ectopy are such that the triggering ectopy can be targeted.10 226 Curr Probl Cardiol, May 2009 Melvin M. Scheinman: Although not addressed by the authors, it is important to emphasize the entity of idiopathic ventricular fibrillation or polymorphous ventricular tachycardia (VT) owing to short coupled PVCs. These patients may have myocardial scar or normal ventricles. The typical patient shows frequent PVCs, usually of the same morphology with a short coupling interval relative to prior QRS. The PVC most often emanates from either the peripheral Purkinje system or the right ventricular outflow region. It is important for the clinician to recognize this entity as it may result in either a cure or a significant amelioration of the arrhythmia. VT ablation usually does not remove the need for an ICD, as there is still a risk of sudden death after VT ablation.11 Success of ablation requires identification and damage to the arrhythmogenic substrate. Mapping refers to the methods for identification of the substrate. In years past, mapping focused on identifying the source of VT during long episodes of VT induced in the electrophysiology laboratory. Ablation was avoided if VT was unstable for mapping due to hemodynamic intolerance, inability to induce VT, or frequent changes from 1 VT morphology to another. Contemporary methods for ablation now often allow ablation of unstable VTs. Ablation can be guided by defining the likely arrhythmia substrate during stable sinus rhythm (commonly referred to as substrate mapping) to target areas for ablation. Multielectrode arrays have been used to assess ventricular activation from a limited number of beats of VT. Judicious use of inotropic agents and devices for hemodynamic support facilitate in mapping some patients. Contraindications to catheter ablation include absence of access to the chamber of interest, such as prior aortic and mitral valve replacement with mechanical prostheses in a patient with a left ventricular tachycardia. In most cases, some vascular approach can be achieved with either transseptal, retrograde aortic, or epicardial access. When these methods are not possible, transcoronary ethanol ablation may be feasible in experienced centers. The presence of mobile thrombus in the chamber is a contraindication to endocardial mapping in that chamber due to the risk of embolism but does not preclude epicardial mapping and ablation. Melvin M. Scheinman: For patients resistant to device, drug or ablative treatments as outlined by the authors, another option is cardiac transplantation. This modality is reserved for the most resistant cases. Most centers would be hesitant to use transcoronary alcohol infusion since the area of infarct produced is less controlled, producing either less than or more than the desired effect. Curr Probl Cardiol, May 2009 227 Comorbid conditions should be taken into account. Increasingly, recurrent episodes of VT are being recognized as a manifestation of end-stage cardiomyopathy. Ablation is not appropriate if a successful procedure is not anticipated to meaningfully improve the patients’ symptoms or survival. Placement of a left ventricular assist device and/or cardiac transplantation is a more reasonable option in some cases. However, catheter ablation may be the only treatment option available when the patient is not a candidate for transplantation or left ventricular assist devices and antiarrhythmic drugs are ineffective. Electrophysiological Substrate of Scar-related Re-entry Sustained scar-related VTs are usually monomorphic and are most commonly due to re-entry involving the scar and surrounding viable myocardium. As for other re-entrant arrhythmias, the following 3 factors facilitate re-entry: (1) slow conduction; (2) areas of conduction block that may be functional or fixed; (3) an initiating mechanism that may be a premature impulse, change in autonomic tone, or particular sequence of R-R intervals.12 Regions of slow conduction can often be identified within a scar. Slow conduction facilitates re-entry because the time required for propagation through slowly conducting regions allows the tissue in the rest of the circuit to recover from each depolarization. Thus, the tissue recovers before arrival of the circulating wave front; otherwise, conduction block would terminate re-entry. Unidirectional block allows initiation of re-entry and areas of persistent block often define the re-entry circuit in areas of scar. Areas of conduction block can be anatomically fixed (present during tachycardia and sinus rhythm) or can be functional (present only during tachycardia or with faster rates).12 Fixed block occurs at anatomical borders (such as the mitral annulus) or dense unexcitable scar. Functional block can occur because of rapid rates such that the tachycardia cycle length is shorter than the time required for recovery at a site (refractory period). Functional block can also occur related to heterogeneous myocyte coupling such that the current available for depolarization is insufficient to bring the adjacent myocyte membrane to depolarization. Collision of excitation wave fronts is also an important source of block. The tissue geometry relative to arrangement of myocyte bundles and areas of fibrosis influences slow conduction and conduction block and is likely a major determinant of whether an area of ventricular scar causes re-entrant VT.13,14 For 228 Curr Probl Cardiol, May 2009 example, when a small myocyte bundle joins a larger bundle, the small bundle may supply insufficient current to depolarize the large bundle with failure of conduction due to “impedance mismatch.” Branching bundles can create the same situation and slow propagation or facilitate conduction block. In addition, fibroblasts in areas of scar may also be involved in slow electrotonic conduction of impulses, or serving as current sinks that influence conduction.15 Melvin M. Scheinman: One other mechanism for initiation of re-entrant arrhythmias is anisotropic conduction. This entity refers to variation in conduction velocity dependent on fiber orientation. For example, while conduction velocity is more rapid when an impulse travels longitudinal to fiber orientation, the safety margin is less robust. If conduction block occurs in the longitudinal direction, slowed conduction may persist in the transverse direction and result in re-entry. Re-entry can be initiated by a premature ventricular contraction that encounters a region of functional block (usually unidirectional block) and propagates around the block through a slowly conducting region, giving the area of block time to recover, so that when the circulating wave front arrives at the opposite side of the region of block, it finds the region recovered and capable of conducting, thus allowing re-entry.12 This is the presumed mechanism by which programmed electrical stimulation initiates re-entry in the electrophysiology laboratory. Interestingly, recordings of spontaneous initiation of monomorphic VT show that the initiating beat of the VT has the same morphology as subsequent VT beats in 30-50% of cases.16,17 These observations suggest that the premature beat often arises in or near the re-entry circuit and that the initiating mechanism may be related to changes in sinus rate and autonomic tone or other factors that influence conduction in the scar region. Melvin M. Scheinman: The observation that a significant minority of initiating PVCs have a contour identical to that of the monomorphic VT is indeed intriguing. It suggests as the authors imply that the patient has concealed re-entry for sinus beats and PVCs and/or VT occurs due to changes that may affect the balance of conduction and refractoriness in the scar border. Re-entry circuits causing sustained monomorphic VT vary in their size, configuration, and locations. A “figure-of-eight” type of circuit has been commonly described and characterized in animal models and has also Curr Probl Cardiol, May 2009 229 FIG 1. Theoretical re-entry circuits as they relate to areas of block and isthmuses are shown. In the schematics on the left the re-entry circuit is indicated by the arrows. Gray regions indicate conduction block that might be from fibrosis, collision of wave fronts, or refractoriness. (A) A simple circuit consisting of a single loop around a region of block. If the loop is broad, ablation in the loop (dotted black line) may increase the re-entry path but fail to interrupt re-entry. (B) A figure-of-eight type of re-entry circuit defined by wave fronts propagating around 2 regions of block and sharing a common isthmus and a common pathway (CP) through which conduction is slowed, creating a “figure-of-eight” configuration. Ablation across the common isthmus (dotted black line) would interrupt re-entry. Ablation in either loop alone leaves the other loop to continue re-entry. (C) A complex circuit with several regions of conduction block along a valve annulus that creates multiple potential channels. (D) Ablation (RF) that interrupts 1 channel and leaves the other potential channels that may support re-entry. (E) Photograph of an explanted heart from a patient who had incessant VT and failed VT ablation with a theoretical re-entry circuit (yellow arrows) is shown. Areas of dense scar, that may form electrically unexcitable scar (EUS), is indicated. A hypothetical channel/isthmus is present between 2 EUS areas. The circulating re-entry wave front propagates through the channel, emerging at the exit to propagate across the ventricles producing the QRS complex. The circulating wave front propagates along the border of the scar (outer loop) to re-enter the channel. A bystander area (black arrow) is also shown. RF lesions failed to interrupt VT, likely related to the location of the re-entry circuit deep to the endocardium. (Color version of figure is available online.) been demonstrated in humans (Fig 1B).12,18 In this circuit 2 loops share a common, critical isthmus that is isolated by 2 lines of conduction block.12 Other types of circuits may comprise a single loop or several loops (Fig 1). In addition, these circuits are 3-dimensional. Often, some 230 Curr Probl Cardiol, May 2009 portions of the circuit are endocardial and others are intramural and even epicardial. Successful catheter ablation is dependent on the identification of regions of the circuit that are critical to re-entry and in a location where they can be interrupted with ablation lesions. For the purposes of mapping and conceptualizing re-entry circuits it can be helpful to define types of re-entry circuit regions.19 Most circuits that can be evaluated with catheter mapping are found to have evidence of an isthmus, also referred to as a channel (Fig 1). The isthmus is a region of abnormal conduction in the scarred area. It can be divided into the following 3 functional sections: an entrance, a central part, and an exit.19 Catheter recordings from an isthmus often reveal low-amplitude, fractionated electrograms (EGMs). Because excitation of the isthmus does not depolarize a large amount of tissue, it does not generate sufficient electrical activity to be detected on the surface electrocardiogram (ECG). The QRS complex only begins when the activation wave front emerges from the isthmus at the exit and propagates away from the exit to the rest of the ventricles.19 The circulating re-entry wave front then returns to the entrance by propagating through an “outer loop” of myocardium along the border of the scar, or through an inner loop that is another channel contained in the scar region. Because the QRS onset occurs after the wave front leaves the isthmus, the isthmus is depolarized before the QRS onset, shortly before the QRS onset (presystolic) near the exit, and earlier in electrical diastole for the central portion of the isthmus. The entrance may be depolarized at the end of the QRS complex or during diastole.20 Thus, during VT, recordings from the isthmus will often show electrical activity during diastole (between the end of the QRS and the onset of the following QRS). The timing of EGMs, however, is not a reliable guide to the re-entry circuit location. Areas of scar also contain regions of abnormal conduction that are not participating in the re-entry circuit but may be depolarized during diastole. These and other regions that are not participating in the re-entry circuit are termed “bystanders” (Fig 1). This situation is further complicated by the fact that a bystander region observed during 1 tachycardia circuit can be a critical isthmus for another tachycardia. Furthermore, a single isthmus region can give rise to more than one QRS morphology of VT. For example, when the circuit revolves in the opposite direction and an entrance becomes an exit. Initial Patient Evaluation Prior to the procedure, the patient’s underlying heart disease should be characterized. In patients with coronary artery disease, the potential for ischemia, which could contribute to instability during the ablation Curr Probl Cardiol, May 2009 231 FIG 2. A flow diagram for VT ablation is shown. The first step is to induce VT to confirm the diagnosis, assess inducibility as an endpoint, obtain the QRS morphology of the VT, and assess His bundle activation. In most cases, VT is terminated by pacing or cardioversion and initial mapping proceeds during sinus rhythm to identify regions of scar (voltage map), potential areas of slow conduction (late potentials, long S-QRS during pace-mapping (PM)), and exit sites (PM sites where QRS morphology resembles that of VT). The catheter is then placed at a likely re-entry circuit site and VT is induced to assess entrainment and/or termination by ablation at that site. If VT is unstable, it is terminated and ablation is performed through the target region. Programmed stimulation is then repeated to determine if ablation has abolished VT and to assess the presence of other VTs. This stepwise approach can be completed for every VT morphology. If VT is stable, mapping may be performed during VT. For patients who have multiple VTs and are unstable, ablation may be guided by the sinus rhythm electrograms and pace-mapping without attempting to induce VT until all potential isthmuses and exits have been ablated. EGM, electrogram; EUS, electrically unexcitable scar; PM, pace-map. procedure, should be assessed. Noninvasive testing is usually the first step. If the noninvasive testing is positive, coronary angiography should be performed with revascularization if necessary. The severity of ventricular dysfunction and location of areas of abnormal wall motion that could potentially contain arrhythmogenic scars should be assessed. Magnetic resonance imaging, echocardiography, and nuclear imaging may reveal areas of scar. Echocardiography is particularly useful to assess the presence of left ventricular thrombi that might increase the risk of embolization during mapping within the ventricle. A mobile thrombus is a contraindication for mapping and ablation in the left 232 Curr Probl Cardiol, May 2009 ventricle. If laminated thrombus is suspected, a period of chronic anticoagulation with warfarin may be considered in the hope of reducing the presence of friable thrombus, but there are no data assessing this approach. Because of concerns about the effects of strong magnetic fields on ICDs, and the large number of implantable devices in this population, magnetic resonance imaging is not usually performed. Assessment of peripheral arterial disease is also an important consideration before the procedure. Access to the LV for endocardial mapping is most commonly achieved retrogradely across the aortic valve. A transseptal approach to the left atrium allowing access to the LV through the mitral valve is also used, particularly for patients with peripheral vascular disease or mechanical aortic valves, or when insertion of multiple mapping catheters is desired. Mapping and Ablation The ablation procedure proceeds in steps. Following vascular access and catheter placement, programmed stimulation is performed to induce the arrhythmia. This step serves the 4 following purposes: confirmation of the diagnosis; allowance of the assessment of the QRS morphology and likely origin of the VT; assessment of hemodynamic tolerance and ability to terminate VT to guide further mapping approaches; and the demonstration that noninducibility is a potential acute endpoint for the procedure. Mapping is then performed to locate the source, either during VT or in sinus or paced rhythm. The VT source is then ablated. Finally, programmed stimulation is performed to determine if the VT is no longer inducible. These steps are reviewed below and summarized in an algorithm in Fig 2. Induction of the Ventricular Tachycardia Most patients with VT and heart disease have an ICD that usually terminates VT within seconds after it occurs. Thus, a 12-lead ECG has often not been recorded and the QRS morphology of the spontaneous, “clinical VT” is unknown. The cycle length and intracardiac EGMs of the VT that are recorded by the device are helpful. However, depending on the adrenergic tone and anti-arrhythmic therapy, the cycle length of the same VT can vary. The EGM morphology from ICD telemetry is limited in its ability to distinguish among different VTs. Stimulation protocols for inducing VT vary. Single and double extrastimuli after a basic drive of 8 stimuli with a cycle length of 400 and 600 ms are commonly employed, followed by the addition of a third extrastimulus.21 Other centers use 4 or more extrastimuli.22 ApproxiCurr Probl Cardiol, May 2009 233 FIG 3. Four morphologically different VTs from different patients are shown. At the top is a schematic of the cross-section of the ventricles. Panel 1, VT originating from the free wall of the RV outflow tract in a patient with arrhythmogenic RV dysplasia. VT has a left bundle branch block configuration in V1. VTs due to coronary artery disease are shown in panels 2-4. Panel 2, VT has a right bundle configuration in V1 with a relatively narrow QRS and axis directed leftward and superiorly. The exit was located at the left side of the interventricular septum. Panel 3, VT also has a right bundle branch block superior axis configuration but is wider than VT in panel 2. The exit was located at the inferior aspect of the left ventricular septum due to an old inferior wall infarct. Of note, in left-sided septal VTs, the QRS can also have a left bundle branch block morphology. Panel 4, VT that has a right bundle branch block configuration (positive in V1) with a frontal plane axis directed inferiorly and rightward. Dominant R-waves are present in the precordial leads. The VT exit was at the posterolateral LV at the mitral annulus in a patient with prior inferior wall infarction. (Color version of figure is available online.) mately 25% of sustained monomorphic VTs require more than 2 extrastimuli for initiation.23 Pacing is commonly performed from 2 right ventricular sites (apex and right ventricular outflow tract) and occasionally the left ventricle.21 234 Curr Probl Cardiol, May 2009 As the stimulation protocol becomes more aggressive, with multiple extrastimuli, sensitivity of initiating VT increases but specificity decreases with the potential initiation of nonspecific arrhythmias, such as polymorphic VT and ventricular fibrillation. However, when the patient has documented VT that is not initiated by routine programmed stimulation, more aggressive stimulation, and the use of beta-adrenergic stimulation with isoproterenol, is often warranted. It is not unusual for VT to be difficult to induce in the laboratory, despite frequent spontaneous occurrences. Sedation and lingering effects of anti-arrhythmic drugs are likely contributing factors. QRS Morphology to Localize VT The QRS morphology of VT is an indication of the location of the circuit exit (Fig 3). VTs with a left bundle branch block-like configuration in lead V1 have an exit in the RV or interventricular septum; dominant R-waves in V1 indicate an LV exit. Bundle branch re-entry (see below) is also an important consideration for VT that has a left bundle branch block configuration. The frontal plane axis indicates whether the exit is on the inferior wall, which produces a superiorly directed axis, or on the anterior (cranial) wall, which produces an inferiorly directed axis. A negative deflection in lead I and AVL indicates a lateral exit. In contrast, if the axis is leftward, the exit is probably near the septum or in the right ventricle. The mid precordial leads, V3 and V4, provide an indication of exit location between the base and apex; apical exits generate dominant S-waves, and basal exits generate dominant R-waves. VTs that originate in the subepicardium generally have a longer QRS duration and slower QRS upstrokes in the precordial leads compared to those with an endocardial exit.24 These generalizations should be viewed only as guides. In a patient with ventricular scars, the QRS morphology can be misleading.25 Melvin M. Scheinman: Attention should be directed at QRS durations that are unexpectedly short (ie, 12 ms). This might be indicative of involvement of the fascicular system. In addition, one should search for the typical patterns of left anterior or posterior hemiblock. A spate of recent reports has emphasized the finding that damage to the specialized conduction system may occur with ischemic heart disease, with postvalvular surgery, as well as in patients with nonischemic cardiomyopathy. In this setting, slowed conduction and conduction block in diseased Purkinje fibers may initiate re-entrant rhythms. In addition, concomitant traditional scar-related as well as fascicular VT may occur. Curr Probl Cardiol, May 2009 235 FIG 4. The effect of manipulating color ranges for voltage maps to expose potential channels and exits is shown. A, B, and C show the same voltage map of the left ventricle viewed from the inferior right anterior oblique perspective. A large inferior wall infarct region is present with electrically unexcitable scar (gray) regions. In (A), dark grey indicates an amplitude 1.5 mV or greater and the lower limit of amplitude (red) is ⬍ 0.1 mV. EGM amplitude through the infarct is heterogeneous. In (B), the lower limit is increased to 0.72 mV, highlighting the border area of the infarct that is likely to contain the VT exit. In (C), the upper limit has been decreased so that an amplitude of more than 0.49 mV is shown as dark grey. A relatively high-amplitude path is present through the infarct region. (D) shows RV paced beat recording (first beat) and pace-mapping (last 3 beats) in the mid-portion of this channel region. From the top are surface ECG leads I, II, III, V1, and V5 and the bipolar recordings from the distal and mid electrode pair of the mapping catheter. Underlying rhythm is paced. A late potential is present (first arrow). Pace-mapping captures a long S-QRS interval of 160 ms, consistent with slow conduction through a channel. (Color version of figure is available online.) Mapping When VT is hemodynamically stable, mapping can be performed during VT, assessing the activation sequence and EGM timing and using entrainment to identify the re-entry circuit. Most patients have 1 or more VTs that are “unmappable” or “unstable” for mapping during VT. Substrate Mapping During Stable Rhythm Substrate mapping refers to methods for identifying the re-entry region during stable sinus or paced rhythm, rather than during VT. This 236 Curr Probl Cardiol, May 2009 FIG 5. Findings from a patient with idiopathic cardiomyopathy and recurrent VT who underwent epicardial ablation after failed endocardial ablation. (A) Left anterior oblique image during right coronary angiography is shown. An ablation catheter (arrow) is shown in the epicardial space. Catheters are also present in the coronary sinus (CS), RV apex, and ICD leads in the right atrial appendage and RV. (B) Recordings during sinus rhythm are shown. From the top are surface ECG leads and bipolar EGMs from the ablation distal (Abl d), mid (Abl m), and distal (Abl d) and RV apex (RVA). Delayed isolated potentials are present during sinus rhythm, as evident on the enlarged inset. (C) Recordings from the same site as in (B). Sustained VT was induced and has a cycle length of 350 ms. Fractionated double potentials are present at the ablation site. The last stimuli of a pacing train at the site are shown. Pacing accelerated all EGMs and QRS complexes to the pacing rate consistent with entrainment. There is no change in the QRS morphology, consistent with concealed fusion. The stimulus to QRS interval is 117 ms, which matches the EGM to QRS interval, consistent with a site in the re-entry circuit. The S-QRS is 33% of the cycle length, consistent with a central portion of the VT isthmus. The PPI is difficult to assess to due saturation of the distal electrode recording from the pacing stimulus. The N⫹1 method for assessing the PPI is demonstrated. The time between the last stimulus and the second beat after the S (which is the first not entrained beat) is 546 ms. This measurement is compared to the interval from the local EGM at the stimulus site in any following beat and the second beat after this local EGM. Here both equals 546, indicating that the site is in the re-entry circuit. (D) shows the 12-lead ECG during entrainment. There is entrainment with concealed fusion. In addition, QRS morphological features consistent with an epicardial re-entry circuit include a relatively late intrinsicoid deflection time in V2 of 92 ms. (E) shows that RF applied at this site terminates VT after 8 s. (Color version of figure is available online.) Curr Probl Cardiol, May 2009 237 technique is particularly useful when VT is hemodynamically unstable, but it is also used in patients with stable VT. It can be combined with other mapping approaches, by locating an initial area of interest and then initiating VT to employ other mapping techniques for further interrogation of the region during VT. Moreover, as many patients have multiple VTs that often share part of the same circuit, substrate mapping can be helpful for targeting more than 1 VT at the same time. Finally, by using substrate mapping in sinus rhythm, the time spent mapping and ablating during VT can be minimized. Mapping systems that re-create the 3-dimensional geometry of the ventricular cavity from point-by-point sampling while providing continuous display of catheter position, can be a great help in substrate mapping. Electrophysiologic data such as the activation time and EGM amplitude are color-coded for display. While helpful, one must be aware of the limitations of these systems. Cardiac and respiratory motion limit the ability to see fine anatomic details such as papillary muscles and valvular structures. Registration of preacquired computed tomography or magnetic resonance images on mapping systems shows promise for improving anatomic definition.26,27 Voltage Maps. Areas of ventricular scar can be identified from anatomic plots of bipolar EGM amplitude. There is an excellent correlation between regions of low-amplitude EGMs and infarct regions in animal models and humans.28-30 More than 95% of sites in normal ventricular regions have a bipolar EGM amplitude ⬎ 1.5 mV.29,30 Voltage maps display peak-to-peak EGM amplitude, thereby identifying regions of infarction or scar (Fig 4). These low-voltage regions often contain re-entry circuits, but they are often too large for ablation of the entire region or its circumference. Additional markers of the circuit exit or isthmus are sought to select regions for ablation. Voltage maps can be created from sinus rhythm, ventricular pacing, or during VT. The change in activation sequence produced by a change in rhythm does alter peak-to-peak EGM amplitude but in our experience does not generally alter the area defined as low voltage based on a threshold of 1.5 mV.31,32 Sinus Rhythm EGM Features of Re-entry Circuit Channels. Areas of slow and heterogeneous activation in areas of scar create EGMs that have multiple components referred to as fractionated. Abnormal EGMs are recorded from re-entry circuit sites; they are common throughout the scar and at bystander sites and are relatively nonspecific. Late potentials and isolated potentials (Fig 5B) that are inscribed after the end of the QRS complex appear to be more specific for re-entry circuit isthmuses/ 238 Curr Probl Cardiol, May 2009 channels.32-35 Ablation targeting these potentials was successful in abolishing previously inducible VT in 21 of 22 patients reported by Arenal and coworkers.33 Channels can also be identified from examining relative EGM amplitudes within regions of scar.36,37 Adjusting the upper threshold in voltage maps can identify channels of relatively greater, although still abnormal, amplitude bordered by low-amplitude areas (Fig 4). Ablation across these isthmuses abolished inducible VT in 16 of 18 patients, reported by Arenal and coworkers.36 Hsia and coworkers successfully identified isthmuses in 56% of patients using this method.37 Melvin M. Scheinman: Proper identification of channel(s) through scarred myocardial regions remains an important problem. These areas may be easily missed depending on setting the appropriate threshold voltage parameters. This problem likely accounts for the relatively high recurrence rate of ventricular arrhythmias even after successful ablation of the clinical tachycardia. It is important to recognize that not all potential channels in a scar cause clinically relevant VTs. Any individual isthmus can be an isthmus of another VT circuit, or a “bystander” channel that does not participate in a clinically relevant VT (Fig 1D). Pace-mapping. Pace-mapping is an excellent tool for targeting idiopathic VTs that have a focal origin in the normal heart.38 Pacing at the focus replicates the VT QRS morphology. It is of prime importance to consider the position of the surface leads, ensuring that they are identical for pace-mapping and recording of the VT, usually requiring induction of VT in the electrophysiology laboratory for ECG recording on the electrophysiology (EP) laboratory mapping system. Melvin M. Scheinman: The point relative to proper surface electrode positioning bears re-emphasis since the patient will have defibrillator pads in the chest wall that might interfere with appropriate lead placement. For purposes of precise mapping, care must be taken to replicate the standard lead positions. In abnormal ventricles pace-mapping is also useful, but with several important caveats.39 Pacing near or at the exit point of a VT circuit should produce a QRS morphology similar to that of the VT.29,39-41 However, when pacing during sinus rhythm in a defined isthmus, the wave front can follow 1 of 2 directions: the orthodromic, which is the same direction as Curr Probl Cardiol, May 2009 239 wave fronts during VT, or an antidromic direction. The wave front is only detected on the surface ECG when it leaves this protected channel. The QRS that will result from pacing in that channel will depend on the degree of fusion of those 2 wave fronts, which depends on the conduction time from the pacing site to the entry and exit sites, and the presence of any areas of fixed or functional block. Activation of the ventricles from the exit region produces a QRS similar to the VT QRS. If the wave front emerges from another region, the QRS will be different from that of VT. If the isthmus during VT is defined by functional block that is absent during sinus rhythm, pace-mapping in the isthmus region is likely to produce a QRS morphology that is different from that of VT. The situation is further complicated by the fact that pacing over a wide area may produce a QRS morphology similar to that of the VT in some patients.42 Bogun and coworkers34 observed that pace-mapping at sites of isolated potentials produced a QRS morphology that was either a perfect or a good match for the VT QRS at 65% of sites with sinus rhythm isolated potentials that were often associated with VT re-entry circuits, compared to only 5% of sites with abnormal EGMs without isolated potentials. However, they also found no difference in outcome between ablating at sites where the pace-map matched VT in all 12 ECG leads (perfect pace-map), as compared to sites with pace-map matches in 10 or 11 of 12 ECG leads (good pace-map).34 Thus, the QRS morphology during pace-mapping can be a guide to a potential exit region or isthmus but can also be potentially misleading. Melvin M. Scheinman: The authors have well summarized the potential problems with pace-mapping for elucidation of the VT exit site. One other point worth mentioning is that careful inspection of the spontaneous VT will often show slight beat-to-beat changes. Hence a 12 of 12 pace-map for 1 complex might be 10 of 12 for a neighboring complex. This might explain the observations by Bogun and coworkers regarding the absence of change in outcomes comparing the different mapping score. Of equal importance would be the interval from stimulus to QRS as discussed in the next paragraph. Pace-mapping can also reveal evidence of slow conduction. The S-QRS interval indicates the conduction time required for the stimulus to propagate away from the pacing site to depolarize sufficient myocardium to be detected in the surface ECG. During pacing in normal myocardial, the S-QRS interval is short, typically ⬍ 40 ms. In a re-entry circuit isthmus, the S-QRS interval is relatively short in the exit region compared 240 Curr Probl Cardiol, May 2009 FIG 6. These 4 panels (from left to right) are from a single patient. The first panel shows the patient’s induced VT that was targeted for ablation. The second and the third panels show pace-maps from 2 different sites. Both show a similar, but not identical, pace-map match for the QRS of the VT, with 2 different S-QRS intervals of 0 in the first and 206 ms (arrow) in the second. These findings are consistent with pacing near an exit site, which explains the short delay. In contrast, in the second pace-map, the catheter is further from the exit, but likely in an isthmus. The last panel shows a pace-map from a different site, which also had an abnormal sinus rhythm EGM (not shown). The QRS morphology is different from VT, but there is a long S-QRS consistent with slow conduction. This site may be in the proximal portion of the isthmus or in an abnormal area that is not involved in this VT (see text for discussion). to sites that are proximal to the exit (Fig 6B and C). In some patients the isthmus and part of its course can be identified by pace-mapping, with a QRS that matches the VT and progressively longer S-QRS intervals as the pacing site moves away from the exit region.19,39 Electrically, Unexcitable Scar. Areas of dense fibrosis that form some re-entry circuit borders can be detected as electrically unexcitable scar (EUS), where pacing does not capture (pacing threshold ⬎ 10 mA at 2-ms pulse width).43 Marking EUS areas creates a visual map of potential channels that might participate in the arrhythmia circuit, in a fashion similar to that described for voltage maps above.43 However, not all scars have large areas of EUS. Narrow bands of fibrosis likely escape detection based solely on pacing threshold. Pacing Considerations for Pace-mapping and Entrainment. Pacemapping can be performed with either bipolar (usually the anode is the proximal electrode and the cathode is the distal electrode) or unipolar Curr Probl Cardiol, May 2009 241 pacing (distal electrode is the cathode and the anode is remote from the heart). During bipolar pacing, myocardium can be captured at the cathode, anode, or both. Kadish and colleagues showed that bipolar pacing can produce a different QRS morphology than unipolar pacing presumably because of anodal capture.44 Anodal capture is potentially an issue because ablation will be performed from only the distal electrode. However, with narrow interelectrode spacings of 1 or 2 mm, common on present mapping catheters, it is unclear if bipolar pacing reduces the reliability of pace-mapping and entrainment mapping (see below). Substrate Mapping Summary. In our center, we create a voltage map with a color scale, which identifies normal myocardium as greater than 1.5 mV; the lower limit of the voltage map is typically 0.1 or 0.5 mV. As the voltage map is constructed, we note the presence of late potentials and isolated potentials at each site with colored tags. Pace-mapping is an integral part of substrate mapping. During creation of the voltage map, we pace at all low-amplitude sites, noting capture, electrically unexcitable areas, QRS morphology, and S-QRS interval. We use unipolar pacing, at 10 mA and 2 ms. The pacing cycle length is typically 600 ms, or faster if required to overdrive sinus rhythm. Although pacing close to the VT cycle length may improve the comparison of the pace-map with the VT QRS, rapid pacing is more likely to induce tachycardia. Areas of electrically unexcitable scar are tagged gray. Once the voltage map is completed, we have often identified the likely exit region for the VTs that have been seen, as well as potential channels. Either these areas can be targeted for ablation or the mapping catheter can be placed at a region of interest and VT can be induced for assessment of that site during VT. Mapping During VT Mapping during VT may include determination of the activation sequence, entrainment mapping, and the noting of sites where mechanical trauma or ablation terminates VT. The extent to which mapping is performed during VT, and which of these methods can be employed, is determined by hemodynamic stability, as well as the stability of the VT. When VT is incessant, mapping is performed during VT by necessity. Activation Sequence Mapping During VT. The onset of the QRS is usually used as a fiducial point for measuring activation times. Activation timing is useful to identify the source of focal VTs, as in idiopathic outflow tract VTs, for which local EGM typically precedes the onset QRS by 20-30 ms at the focus and activation is progressively later as the site is moved away from the focus.45 242 Curr Probl Cardiol, May 2009 In contrast, in scar-related re-entry, there is no earliest point in the circuit. Presystolic electrical activity, before the onset of the QRS, is typically recorded from the exit region. Activation of the ventricles and outer loops in the re-entry circuit typically occurs during the QRS complex. Presystolic EGMs can also originate from bystander regions. Therefore, the presence of presystolic activity alone is a poor predictor of VT termination by radiofrequency (RF) ablation.46,47 Focusing only on sites that display presystolic electrical activity ignores portions of the re-entrant circuit that are proximal to the exit, that may be depolarized during the end of the QRS complex.20 An isolated, low-amplitude diastolic potential is often a marker of a narrow isthmus in a re-entry circuit (Fig 5C).47,48 Isolated diastolic potentials are found in more than 50% of isthmus sites.49 However, even if they are more specific, they still can be present at some bystander sites and occasionally at outer loop and inner loop sites.46 Entrainment mapping can usually determine if the diastolic potential originates from inside the re-entrant circuit or at a bystander site. Inability to dissociate the potential from the tachycardia by pacing remotely from the circuit also suggests that the potential originates from the re-entry circuit.47 Melvin M. Scheinman: A constant relationship between the potential and succeeding QRS complex of VT is strong evidence that the potential is part of the circuit. This may be seen, as the authors state, by remote pacing but may also be seen during spontaneous changes in VT rate, especially at initiation of the tachycardia. Interpretation of activation is further complicated by the presence of far-field electrograms (see below). Both of these concerns can be recognized from entrainment mapping.50 When VT is stable for mapping, the entire circuit can occasionally be defined, with the activation sequence encompassing the tachycardia cycle length.18,22 More commonly only limited portions of the circuit are identified. Extensive characterization of endocardial activation from 1 or a few beats can be achieved using multielectrode arrays, including “noncontact” mapping systems that mathematically reconstruct potentials at a distance from the sampling electrode array. These systems identify endocardial exit regions of presystolic electrical activity in more than 90% of VTs.51-53 Some diastolic activity is identified in approximately two-thirds of patients, but complete re-entry circuits are defined in fewer than 20% of patients, likely due Curr Probl Cardiol, May 2009 243 FIG 7. Pacing for entrainment mapping during VT is shown. In the top panel, the pacing cycle length is 590 ms. Although a cursory assessment suggests entrainment with concealed fusion, in fact, that VT cycle length is 570 ms and pacing does not capture and is therefore not useful for mapping. In the middle panel, pacing captures and accelerates the QRS complexes and EGMs to the paced cycle length. The VT cycle length is 520 ms. The PPI is 534 ms, consistent with a site in the circuit. Subtle QRS fusion is present with a slight change in QRS morphology. These findings are consistent with an outer loop site. The lower panel shows findings from another site. Presystolic EGMs are present with an EGM to QRS interval of 107 ms (asterisk and arrow). Pacing accelerates all QRS complexes and EGMs to the paced cycle length. The PPI of 520 ms, with a VT cycle length of 520 ms, is consistent with a site in the circuit. There is no change in QRS morphology, consistent with concealed fusion. The S-QRS interval equals the EGM to QRS interval of 107 ms, also consistent with a re-entry circuit site. (Color version of figure is available online.) 244 Curr Probl Cardiol, May 2009 to the low-amplitude signals that are not detected from some isthmus regions, or intramural or epicardial locations of portions of the circuit.53 Melvin M. Scheinman: Other problems relating to the noncontact mapping system relate to changes in the activation pattern depending on changes in filter frequency used. In addition, contamination with far-field atrial signals may affect the map. Entrainment Mapping. Entrainment is the continuous resetting of a re-entrant circuit by a train of capturing stimuli. Entrainment is most consistent with re-entry as a tachycardia mechanism.54 During entrainment, the stimulated wave front arrives at the re-entry circuit and splits into 2 wave fronts: the orthodromic wave front travels in the same direction as the tachycardia wave fronts in the circuit. The stimulated antidromic wave front travels in the opposite direction in the circuit. The antidromic wave front collides with a returning orthodromic wave front and is extinguished. The orthodromic wave front propagates though the circuit, resetting the circuit. The depolarization of the ventricles by these 2 wave fronts produces fusion. Waldo has developed the 4 following classical criteria for entrainment. The presence of any 1 of them confirms entrainment and supports re-entry as the mechanism of tachycardia.54 1. Constant QRS fusion during pacing at a constant rate faster than the tachycardia and that does not terminate tachycardia. 2. Different degrees of fusion during pacing at different rates that fail to terminate the tachycardia, also known as progressive fusion. The contribution of the paced QRS morphology increases relative to the VT QRS morphology as the rate of the pacing is increased. 3. The EGM equivalent of progressive fusion, demonstrated when pacing from the same site at 2 different rates produces stable activation at a remote site, but with a different S-EGM interval and/or EGM morphology, indicating that the activation is different. 4. Pacing interrupts tachycardia with a characteristic finding of localized conduction block to a distant site, indicated by failure of the stimulus to depolarize the distant site, followed by activation of the site from the next stimulus with a shorter stimulus-to-EGM interval. Post Pacing Interval. The post pacing interval (PPI) is an indication of the proximity of the pacing site to the re-entry circuit.46,55 It is measured Curr Probl Cardiol, May 2009 245 FIG 8. Entrainment with concealed fusion is shown. At the top are schematics (A and B) of a double loop re-entry circuit. Pacing is performed at a site in the common isthmus. Orthodromic propagation is indicated by black arrows. Antidromic activation is indicated by the gray arrow. Conduction block is indicated by gray regions. During pacing, the stimulated orthodromic wave front propagates to the exit, such that the QRS morphology is the same as VT. The S-QRS delay is due to the conduction time from the pacing site to the exit. After the last stimulus (B), the PPI is equal to 1 revolution through the circuit, which approximates the tachycardia cycle length. (C) is a tracing showing the last 2 stimuli of a pacing train that entrained VT. From the top are surface ECG leads and intracardiac recordings from the mid (maps 2-3) and distal (maps 1-2) electrode pair of the mapping catheter. Pacing entrains tachycardia with concealed fusion. A far-field potential (asterisk) (FFP) is present at the recording site, confirmed as a far-field potential because of the following: (1) it is not depolarized during the pacing drive and (2) the PPI calculated using this potential would be shorter than the actual TCL. (A) indicates that the FFP could potentially be due to depolarization of tissue in an outer loop or remote from the circuit. The local potential (arrow) is not visible during pacing and reappears after the last entrained QRS complex. In this case the FFP has substantially greater amplitude than the local potential. (Color version of figure is available online.) from the last pacing artifact of an entrained beat to the local EGM of the next beat at the pacing site. Pacing of re-entry circuit sites, this interval is the time from the stimulated orthodromic wave front to make 1 revolution through the re-entry circuit. Therefore, the PPI should be equal to the VT 246 Curr Probl Cardiol, May 2009 cycle length (TCL) (Figs 7B, C and 8). In contrast, at sites remote from the circuit where pacing entrains the tachycardia, the PPI is increased by the conduction time from the pacing site to the re-entry circuit and back from the circuit to the pacing site.46 Thus, the longer the conduction time from the pacing site to the circuit (and likely the further the pacing site from the circuit), the longer the PPI-TCL.46 For postinfarction VT, an isthmus site with a PPI-TCL of less than 30 ms is associated with termination of tachycardia by RF ablation, thereby indicating close proximity to the re-entry circuit. However, the PPI-TCL does not identify whether the site is a narrow isthmus or a broad path in an outer loop in the circuit; analysis of QRS fusion is necessary for that determination. At outer loop sites the PPI indicates that the site is in the circuit, but entrainment occurs with QRS fusion. The S-QRS interval is also typically short due to rapid progression away from the stimulus site that is usually in the border of the scar region. Caveats of PPI Interpretation. Three fundamental assumptions must be valid for the PPI to be a reliable indication of proximity to the re-entry circuit. First, pacing captures and accelerates all EGMs and QRS complexes to the pacing rate (Fig 7). Second, pacing does not alter conduction through the re-entry circuit. The PPI will prolong if pacing slows conduction in the circuit due to decremental conduction properties, or extension of lines of functional block elongating the re-entry path. Entrainment for measurement of the PPI usually uses pacing only slightly faster than the tachycardia cycle length to avoid altering the circuit or terminating tachycardia.56 The third assumption is that the EGM selected for measurement indicates activation at the pacing site, requiring the recognition of far-field potentials.50,57 Far-field Potentials. As discussed above, EGMs recorded from areas of scarring often contain multiple potentials that reflect depolarization of myocyte bundles that are separated by areas of dense fibrosis and consequently depolarized at different times.58 The amplitude of each potential is determined by the mass of tissue generating it, and the orientation and proximity of the recording electrodes to that tissue. Far-field potentials are due to depolarization of tissue that is remote from the recording electrode. The relative amplitude of the different potentials does not reliably identify the far field potential from the local potential in the EGM that is produced by depolarization of the tissue beneath the recording electrode. A large mass of normal myocardium at the border of the scar and remote to the electrode may produce a larger potential than the local EGM (Fig 8). These “far-field potentials” are a source of error in activation mapping and measurement of the PPI.50,57 Curr Probl Cardiol, May 2009 247 Far-field potentials can often be recognized during entrainment. The EGM from the local potential is directly depolarized by the pacing stimulus and is obscured during pacing (Figs 8 and 5C). When the stimulus strength is sufficient to capture, far-field potentials are signals that are evident during pacing and are not directly depolarized by the voltage gradient from the stimulus.50 If the PPI is shorter than the actual cycle length of the tachycardia, it is likely that a far-field potential was used for the measurement and is therefore not an indication of whether the site is in the circuit. Far-field potentials have also been recognized by the lack of effect of ablation on the signal.35,50 Assessing PPI Despite Stimulus Artifact. Validity of the PPI-TCL difference is based on the assumption that the recorded EGM represents depolarization of the pacing site. However, recording from the stimulus site is not always interpretable or even obtainable due to electrical noise after the stimulus artifact. The PPI-TCL difference can be calculated from EGM that is recorded by the electrode that is adjacent to that used for pacing (proximal electrodes of the ablation catheter while the distal are used for pacing).57 However, in approximately 15% of cases the distal and proximal electrode recordings do not agree sufficiently for this approach to be considered reliable; it does introduce some error related to the distance between the recording electrodes. Alternatively, there is excellent agreement between the PPI-TCL difference and a measure termed the N⫹1 difference.59 For this technique the conduction time between the last stimulus (S) that entrains tachycardia and any reliable reference point on the QRS or intracardiac EGM of the second beat after the stimulus (N⫹ 1 beat reference point) is determined (Fig 5C). Moving to a point where the recordings from the distal electrodes of the mapping catheter are visible, the N⫹1 reference point is identified and the point that precedes the reference point by the N⫹1 interval is identified. The interval between that point and the local EGM equals the PPI-TCL difference.59 This measurement is a modification of the S-QRS measure proposed by Fontaine and colleagues discussed above60 but is valid when entrainment occurs with QRS fusion as well as without QRS fusion and allows an intracardiac EGM to be used as a reference point (Fig 5C). Entrainment with Concealed Fusion. During entrainment, the QRS complex is a product of the wave fronts that emerge from the tachycardia exit (orthodromic wave fronts) and the stimulated wave fronts from the pacing site. The morphology of a fused QRS can provide useful information on the location of the pacing catheter in relation to the site of the tachycardia circuit. The further the pacing site from the re-entry 248 Curr Probl Cardiol, May 2009 circuit exit, the more the paced beat will likely differ from the VT beat. During VT, fusion from a remote site is usually obvious. By pacing near the circuit exit, or at outer loop sites in the circuit, minimal QRS fusion can be present. Pacing in the re-entry circuit isthmus, however, entrains the tachycardia without changing the QRS morphology (Figs 5D-7C) because the stimulated orthodromic wave fronts leave the circuit from the re-entry circuit exit, and the stimulated antidromic wave front is contained in or near the circuit by collision with returning orthodromic wave fronts. This phenomena has been called entrainment with concealed fusion (ECF), concealed entrainment, or exact entrainment.46,61 ECF often identifies exit or isthmus sites. However, ECF can also be seen at inner loop sites or adjacent bystander sites. Another limitation is that a subtle amount of QRS fusion may be difficult to appreciate in the ECG. Ormaetxe and coworkers have shown that QRS fusion is reliably detected only when more than 22% of the QRS is fused.62 Analysis of all 12 surface ECG leads may improve the detection of fusion. Additional analyses of the PPI or S-QRS and EGM-to-QRS interval are used to determine if an ECF site is an isthmus in the circuit. During ECF, the S-QRS interval indicates the time required for the stimulated wave front to propagate from the pacing site to the circuit exit. Similarly, the interval from depolarization at the pacing site to the QRS onset describes the same activation time. Thus, these 2 intervals match for ECF sites that are in the re-entry circuit.46,60 ECF sites that are bystanders are not common but can be recognized by a difference in S-QRS compared to EGM-QRS intervals at the pacing site. The indication of the conduction time between the pacing site and re-entry circuit exit shown by the S-QRS can be used to classify the pacing site position as in the exit [S-QRS ⬍ 30% of the VT cycle length (CL)], central (30-70% of the VT CL), or inner loop (⬎ 70% of the VT CL). Integrating Mapping and Ablation For re-entrant VTs, the goal of ablation is to interrupt the circuit. Theoretically, the circuit can be interrupted at more than 1 site but is most likely to be susceptible to ablation lesions of a limited size in the isthmus where the re-entry path is narrow.19 The central isthmus or exit is the location that is usually chosen for ablation of scar-related tachycardia. If VT is stable or can be tolerated for a brief period, we often apply RF lesions during VT, as termination of VT provides further evidence that the site is in the tachycardia circuit.63,64 Ablation in outer loops is usually not effective, unless the entire loop Curr Probl Cardiol, May 2009 249 TABLE 1. Common characteristics of re-entry circuit sites during substrate mapping and mapping during VT VT mapping Substrate mapping Entrainment Pace map VT Mapping QRS Late PPI S-QRSⴝ Locations\ matches isolated Presystolic Diastolic Concealed VT EGMCharacteristics VT potentials potentials potentials fusion CL QRS Isthmus Exit Outer loop Inner loop Bystander ⫹\* (long S-QRS) ⫹ ⫺ ⫹ ⫹\⫺ ⫹ ⫹/⫺ ⫹/⫺ ⫹\⫺** ⫺ ⫹/⫺ ⫹/⫺ ⫺ ⫹\⫺ ⫹\⫺ ⫹ (can be ⫹ (S-QRS late ⬎ 0.3⫻ systolic) VTCL) ⫺ ⫹ (S-QRS ⱕ0.3⫻ VTCL) ⫺/⫹ ⫺ ⫹/⫺ ⫹ ⫹/⫺ ⫹\⫺** ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫺ N/A*** ⫹ ⫺ or N/A ⫹ Characteristic is usually present. ⫺ Characteristic is usually absent. CL ⫽ cycle length. *At an isthmus location, the paced QRS often resembles VT, particularly if near the exit. At sites proximal to the exit, the wave front may leave the scar from a different site, producing a different QRS configuration. **A bystander location can mimic the tachycardia if it is close to the circuit. ***S-QRS ⫽ EGM-QRS can only be used when concealed fusion is present. can be transected. Even isthmuses can be relatively broad, requiring multiple RF applications. Mapping stable VTs, de Chillou and coauthors found isthmuses with an average width of 16 mm (ranging from 6 to 36 mm).18 Therefore, we usually place a line of lesions across the isthmus when ablating scar-related VT. Valve annuli often form one border of an isthmus, providing a convenient anchor point for an ablation line through an isthmus. When VT is related to previous inferior wall infarction, an isthmus is often present running perpendicular to the mitral annulus, such that an RF lesion line that is perpendicular to the mitral annulus toward the apex into the scar will interrupt that isthmus.65,66 RF applications are usually confined to low-voltage scar areas, in the hope of avoiding damage to contracting regions of myocardium. The precision of mapping data, the reliability of the isthmus location, and the characteristics of the isthmus dictate the extent of RF lesions required. Direct comparisons of the outcomes for different mapping approaches to guide ablation are difficult, as the approaches are often determined by the nature of the arrhythmia and the patient’s stability. For unstable VTs Marchlinsky and coauthors created voltage maps and placed RF lines connecting the lowest amplitude areas to a valve annulus 250 Curr Probl Cardiol, May 2009 or regions of normal voltage and extending through margins of the scar where the pace-map matched the VT QRS complex.29 A median of 4 lines were placed with a median of 55 RF applications in 16 patients.29 During a median follow-up of 8 months (3-36), 12 of 16 patients (75%) were free from recurrent VT. Volkmer and coworkers reported similar outcomes with acute success for 79% of patients with ablation of postmyocardial infarction VT guided by substrate mapping for 25 patients with unstable VTs versus mapping during VT in 22 patients who had stable VTs.67 We and many centers use a combination of mapping modalities (Fig 2, Table 1) that seeks to minimize the amount of time that the patient is in VT, to reduce the number of attempted VT inductions, and to reduce the potential initiation of ventricular fibrillation or rapid VTs requiring cardioversion; and seeks to ablate all monomorphic VTs.64,68 First, VT is induced to confirm the diagnosis and assess QRS morphology, which is also used to guide pace-mapping. A substrate mapping approach is performed, even if VT is stable, to identify areas of scar, likely exits, and isthmuses. Additional assessment is then performed during induced VT with limited entrainment mapping and ablation during VT to assess termination of VT when feasible. Even some unstable VTs can be induced for short periods and then entrained after substrate mapping has identified the region of interest. When a potential isthmus or exit is targeted, RF lesions are placed in that region, with evidence of ablation sought by absence of capture during pacing at 10 mA. This approach was assessed in 40 patients with prior infarction who had 143 different inducible VTs, only 40 of which were stable for mapping.64 An isthmus was identified in 63% of the cases and ablation abolished or modified that VT in all cases with a recurrence rate during follow-up of 28%. In contrast, when an isthmus was not identified and ablation lines placed at the best pace-mapping sites, more extensive ablation was performed, and there was a trend to worse outcomes with 53% of patients having recurrent VT during an average follow-up of approximately 10 months.64 Melvin M. Scheinman: The authors’ experience is reflective of the general experience, namely, multiple VT are initiated during study and the overall success rate is between 50 and 75% dependent on successful ability to locate a VT isthmus. The chief problems relate to proper identification of responsible channels in the area of scar and/or presence of intramural or epicardial circuits. Curr Probl Cardiol, May 2009 251 Creating Effective Ablation Lesions Successful ablation requires creation of an adequate lesion. Lesion creation is indicated by termination of tachycardia, a reduction in EGM amplitude, or an increase in pacing threshold. Even if the VT terminates during the first application, we usually place additional lesions if pacing continues to capture. We consider a unipolar pacing threshold greater than 10 mA at 2-ms pulse width to indicate creation of a lesion.69 The location of re-entry circuits deep within the myocardium or in the subepicardium is a major cause of failure of ablation for scar-related VTs. Technologies that attempt to increase lesion size can be expected to facilitate interruption of scar-related VT circuits. Most centers use irrigated RF catheters or large-tip electrodes, which allow greater power application. Irrigated Tip Catheter Ablation RF lesions are created by resistive heating within the tissue. The catheter electrode heats because of its contact with the tissue. When the catheter electrode surface temperatures exceed 75°C, proteins coagulate on the electrode and form a high impedance barrier, limiting further energy delivery, causing an “impedance rise.” Cooling the ablation electrode by irrigating it with room temperature saline allows greater energy application before coagulum formation occurs, facilitating creation of larger lesions. Lesion depths up to 7 mm have been observed in a human heart explanted for transplant.70 Standard RF typically produces lesions approximately 3 mm deep.71 Cooled RF ablation has been shown to be more effective in acutely terminating VT than ablation with a solid 4- or 5-mm electrode.72 However, irrigated electrodes are prone to cause deep heating within the tissue that can lead to steam formation that can explode through the tissue (“steam pops”).73,74 Tamponade can occur but is rare during ablation of scar-related LV tachycardia. The risk is likely greater in the thin-walled RV and with power exceeding 40 Watts. There are 2 types of irrigated catheters. With externally irrigated catheters, saline flows through pores in the electrode into the bloodstream. In animal models this is associated with reduced risk of thrombus formation.74 External irrigation administers a volume of saline intravascularly, requiring careful attention to the volume status of the patient and often diuresis, particularly for patients with heart failure. Extensive ablation in patients with renal insufficiency (serum creatinine ⬎ 2.5 mg/dL) is not recommended due to the limited ability to manage the intravascular volume load. An internally irrigated catheter does not administer intravascular volume but does not appear to cool the electrode or prevent thrombus formation as effectively.74 252 Curr Probl Cardiol, May 2009 Large (8- or 10-mm electrode tip) electrodes have also been used for ablation of scar-related VTs. Increasing electrode tip size exposes more electrode surface area to the cooling effects of the surrounding intracavitary blood flow, allowing greater energy application to the tissue. Temperature disparities across the electrode can foster coagulum formation, which is, in our experience, common during high-power prolonged applications with stable catheter position during ablation of atrial flutter.75 The larger electrode also theoretically reduces the resolution for mapping. Epicardial Mapping and Ablation Epicardial re-entry circuits are common in VT due to nonischemic cardiomyopathy, and in approximately 15% of VTs due to coronary artery disease, contributing to failure of endocardial ablation.76-78 Initial myocardial depolarization from an epicardial VT occurs further from the endocardial Purkinje system, such that greater delay in ventricular activation can be expected. Several ECG features also suggest an epicardial circuit.24,79 Epicardial VTs tend to have wider QRS complexes than endocardial VTs with a slower initial QRS deflection, giving rise to 2 criteria. A pseudodelta wave of more than 34 ms in duration is quite specific for epicardial VT, but less sensitive than an intrinsicoid deflection time of more than 85 ms in V2 (Fig 5D).24 For outflow tract VTs, an epicardial origin is suggested by a prolonged precordial maximum deflection index (⬎ 0.55), calculated by dividing the earliest time to maximum deflection in any of the precordial leads by the total QRS duration.79 Whether this holds true with scar-related outflow tract VTs is not clear. Epicardial circuits can be approached in the electrophysiology laboratory with the percutaneous technique described by Sosa and colleagues.78 The pericardial space is entered with an epidural needle under fluoroscopic imaging with contrast injection, followed by placement of a guide wire and introducer sheath for the mapping catheter. Mapping can be done in the same integrated method that was described previously for endocardial mapping. In the absence of adhesions, the catheter moves freely in the pericardial space. This approach may not be possible if adhesions from prior cardiac surgery or pericarditis are present. A surgical pericardial window can be used in this situation.80 Epicardial ablation with standard solid RF ablation electrodes can be successful, but absence of cooling from circulating blood often results in low power heating with the creation of small lesions, requiring irrigated RF ablation.81 Irrigated RF ablation has been used successfully and is our preference. If external irrigation is used, we insert an 8.5-F sheath that Curr Probl Cardiol, May 2009 253 allows the irrigant to be periodically aspirated from the pericardial space during ablation. With internal irrigation, pericardial drainage is not needed. Significant complications are infrequent, but the reports are derived from a relatively small number of experienced centers. The risk of injury to epicardial coronary arteries is a major concern and is dependent on proximity to the vessel, overlying fat, and vessel diameter, with smaller vessels more susceptible to thermal injury.82,83 Proximity to the coronary arteries is assessed by angiography while the ablation catheter is at the target site; ablation directly on major vessels is avoided (Fig 5A). The left phrenic nerve courses down the lateral aspect of the LV and can be identified by pacing from the ablation catheter so ablation at the nerve can be avoided to reduce the risk of injury. Pericardial bleeding can occur but rarely requires prolonged drainage or surgical treatment. Rare cases of significant subdiaphragmatic bleeding related to puncture of subdiaphragmatic vessels have occurred. After ablation, symptoms of pericarditis are common but generally resolve within a few days. Administration of a nonsteroidal anti-inflammatory agent and occasionally stronger analgesics is sometimes required. Intramural Ablation VT that originates from deep intramyocardial regions, as within the interventricular septum, may not be effectively ablated by an endocardial or epicardial approach. Retractable infusion-needle catheters are being studied in animals to address intramural substrate.84,85 Transcoronary ethanol ablation is an option in experienced centers, but the risks and efficacy are not well defined.86 In a recent series Sacher and coworkers obtained acute success in 56% of patients (89% for clinical targeted VT) despite prior failed RF ablation.87 Remote Magnetic Navigation Catheter ablation requires advanced skill in catheter manipulation. Remote navigation systems that allow computer-facilitated catheter guidance offer the potential of facilitating catheter mapping. One system uses flexible catheters and magnetic guidance to orient the catheter in an external magnetic field.88,89 Feasibility of VT mapping with this system was reported.88 It also offers the potential, when combined with a 3-dimensional mapping system, of reducing fluoroscopic imaging.88 There is also the theoretical possibility of less traumatic endocardial mapping, avoiding tachycardia termination by mechanical “bumping.” Further studies of ablation with the system are needed. 254 Curr Probl Cardiol, May 2009 Minimizing Risks Hemodynamic Support Hemodynamic status should be optimized before ablation when possible. In tenuous patients, placement of a pulmonary artery balloon catheter for monitoring filling pressures is reasonable. When systemic blood pressure is marginal, with sedation or following VT episodes, inotropic agents, such as dopamine, can be used to increase blood pressure during VT and facilitate stability during the procedure. We have occasionally used intra-aortic balloon counterpulsation to provide hemodynamic stability during slow incessant VT. Use of percutaneous left ventricular assist devices to provide support for mapping unstable VTs in the electrophysiology laboratory has also been reported.90 The benefits and risks of these devices should be carefully considered before implementation. Thromboembolism and Anticoagulation Systemic thromboembolism causing stroke was observed in 2.7% of 146 patients in 1 multicenter trial of ablation for postinfarction VT using an internally irrigated ablation catheter.91 In a study of 226 patients undergoing ablation using an externally irrigated ablation catheter no strokes were observed.92 Echocardiography to assess the presence of left ventricular thrombus is warranted before endocardial LV ablation. Systemic anticoagulation with heparin is mandated during all left ventricular endocardial ablation procedures. In the presence of severe peripheral vascular disease, a transvenous approach with atrial transseptal puncture for access to the endocardial LV removes the risk of embolism from aortic thrombi. Platelet and fibrin thrombi can form on the surface of RF ablation lesions.72 Some form of anticoagulation is generally employed for a minimum of 6 weeks after VT ablation, especially if ablation is performed on the left side of the heart. Warfarin is generally recommended if extensive RF lesions are made, or if the patient is at high risk for thrombus in the left ventricle, as when it is severely dilated. Aspirin alone has been used in lower risk situations. Management of Anti-arrhythmic Drug Therapy Most patients referred for VT ablation are failing anti-arrhythmic drug therapy. Discontinuing antiarrhythmic drug therapy before ablation is usually attempted to reduce the possibility that drugs will suppress Curr Probl Cardiol, May 2009 255 inducible arrhythmias, impeding mapping and assessment of ablation effects. When VT is frequent, drug withdrawal before the procedure is not always feasible. Following successful ablation, antiarrhythmic drugs may be discontinued. For amiodarone, the long half-life results in a slow taper of drug effect. In some cases a drug that failed before ablation effectively prevents recurrent VT during follow-up. Marchlinski and colleagues observed more VT recurrences after discontinuing anti-arrhythmic drug therapy after ablation.93 Complications of Ablation Complications for VT ablations can be divided into 2 main categories. Some are related to vascular access (thrombophlebitis, femoral artery pseudoaneurysm, and dissection). Others are inherent to the ablation itself. Due to longer procedure times, extensive ablation in the left-sided circulation, the presence of structural heart disease, and the high prevalence of comorbidities in this population, the procedural risks of VT ablation are higher than for most other electrophysiologic procedures. In the 1998 North American Society of Pacing and Electrophysiology (NASPE) Prospective Catheter Ablation Registry, significant procedural complications were observed in 3.8% of patients undergoing a ventricular tachycardia ablation.94 However, this registry included idiopathic VT patients. Melvin M. Scheinman: The NASPE registry that the authors allude to comprised less ill patients and less complex cases compared to cases undertaken by current investigators. This likely explains the lesser incidence of significant complications described in the registry. The complication rate is likely greater in a sicker population. A multicenter trial reported an incidence of major complications of 8% (leading to death in 2.7% of the patients) and a 6% rate of minor complications.91 The most significant complications were strokes (2.7%), cardiac tamponade (2.7%), inadvertent complete heart block (1.4%), myocardial infarction (0.7%), and aortic valve injury (0.7%).91 Other less frequently reported complications include heart failure, cardiogenic shock, coronary artery embolism, and catheter entrapment in the mitral apparatus. The incidence of complications likely varies greatly with operator experience and patient comorbidities. 256 Curr Probl Cardiol, May 2009 Inducible Ventricular Tachycardia and Ablation Endpoints Multiple potential re-entry circuits are often present in patients with scar-related VTs. A median of 3 different monomorphic VTs are usually inducible with repeated attempts. VTs with a similar morphology and rate as those that have been observed to occur spontaneously are often referred to as “clinical VTs.” Other VTs are often designated “nonclinical.” Often, however, the relation between induced and spontaneous VTs cannot be established with certainty because VT is terminated by an ICD without ECG documentation. In addition, “nonclinical” VTs may subsequently occur spontaneously.95,96 Reported endpoints and definitions of successful ablation vary. Most studies define the VTs that were targeted for ablation. Abolishing incessant VT and inducible “clinical” VT is the minimum endpoint for acute success.34,97 Other centers target all inducible VTs, or all inducible mappable VTs, in the hope of reducing recurrence.64,98-100 These different endpoints have not been directly compared. After ablation, at least 1 VT is no longer inducible in 73-100% of patients and no VT is inducible in 38-95% of patients. VTs that remain inducible are often faster than those induced before ablation and may require more aggressive stimulation.22,98,100,101 If the targeted VT remains inducible after ablation, the risk of recurrence exceeds 60%.95,102 Absence of any inducible VT is associated with a lower incidence of recurrence ranging from 3-27% in single center reports.22,43,95,98,100,102 The presence of inducible, “nonclinical” VTs is associated with increased risk of recurrence in some studies.100,103 Healing of initial ablation lesions and reduction of antiarrhythmic medications likely contribute to recurrences. Some patients benefit from a repeat procedure. In some patients VT recurs but the frequency of episodes is substantially reduced.22,29,91,104 In a multicenter trial of 146 patients, inducible VT after ablation did not predict recurrences. VT recurred in 44% of patients with no inducible VT and in 46% of those with inducible VT after ablation.91 During short-term follow-up the frequency of spontaneous VT was reduced by more than 75% in most patients. Ablation in Specific Disease Most of the scars that provoke ventricular arrhythmias are of ischemic origin. Nevertheless, other processes can also be responsible for scarCurr Probl Cardiol, May 2009 257 related tachycardia. Arrhythmogenic right ventricular dysplasia, cardiac sarcoidosis, and surgical scars can be the substrate of ventricular arrhythmias as well. Postmyocardial Infarction Patients with infarct related-scarring, referred for ablation, have generally failed drug therapy and remain symptomatic despite an ICD. Ablation is acutely successful, abolishing 1 or more VTs in 77-95% of patients. During follow-up, previously ineffective antiarrhythmic drugs, frequently amiodarone, are often continued. VT recurs in 19-50% of patients, although in the majority, the frequency is reduced. Failure of endocardial ablation can be due to intramural or epicardial re-entry circuits. Epicardial circuits are present in 10-30% of patients, more often in inferior-wall as opposed to anterior-wall infarctions.76,78 During long-term follow-up, heart failure is a major cause of death, occurring in approximately 10% of patients annually.105 The substantial mortality is consistent with severity of ventricular dysfunction and the recent recognition that recurrent ventricular arrhythmias are a marker for mortality and heart failure.7 Confining ablation lesions to areas of low-voltage scar in the hope of reducing any potential impact on ventricular function and attention to appropriate therapies for ventricular dysfunction are important in this patient population. Nonischemic Dilated Cardiomyopathy Sustained monomorphic VT is uncommon in nonischemic dilated cardiomyopathies, but 60-80% of those that occur are due to scar-related re-entry, with the remainder due to bundle branch re-entry or a focal origin.80,106-108 Myocardial scar has been demonstrated with magnetic resonance imaging and is frequently abutting a valve annulus.108,109 Progressive replacement fibrosis is a likely cause. VT ablation is often more difficult than in coronary artery disease, but recurrent arrhythmias are controlled in more than 60% of patients.80,106 Re-entry circuits are epicardial in location in a third or more of those patients. Bundle Branch Re-entrant Ventricular Tachycardia Bundle branch reentry tachycardia causes 5-8% of all sustained monomorphic VTs in patients referred for electrophysiological study.110,111 Underlying heart disease is present in almost all the cases, with coronary artery disease most common, but dilated cardiomyopathies, muscular dystrophies, and valvular heart disease are also important underlying diseases.110 258 Curr Probl Cardiol, May 2009 FIG 9. Typical bundle branch re-entry is shown. VT has a left bundle branch block configuration. A His bundle deflection is present before the QRS. Oscillation in the H-H interval, increasing from 426 to 398 ms, precedes the QRS oscillations, confirming that the His bundle is closely linked to the circuit. The inset shows simultaneous recordings from the His bundle and the ablation catheter proximal (Abl p), mid (Abl m), and distal (Abl d) electrodes and the RV catheter (RVA) that are lying along the course of the right bundle branch. Activation proceeds from the His anterogradely in the right bundle branch. (Color version of figure is available online.) It is important to have a His bundle catheter in position to make the diagnosis (Fig 9). Most commonly the circulating wave front propagates up the left bundle branch and antegradely down the right bundle branch, producing VT with a QRS configuration of typical left bundle branch block. Less frequently the circuit revolves in the opposite direction, producing a right bundle branch block configuration. Ablation of the right or left bundle branch is curative, but ablation of the right bundle is generally preferred to avoid hemodynamic consequences of left bundle branch block. The HV interval typically prolongs and implantation of a pacemaker is often warranted. Approximately a third of patients have other, scar-related VTs warranting ICD implantation as well. Rarely, re-entry occurs between 2 fascicles of the left bundle branch system alone, requiring ablation of a portion of the left bundle branch. The Purkinje system may also function as a portion of a scar-related re-entry circuit in postinfarction monomorphic VT.112 Melvin M. Scheinman: Although uncommon, the clinician should always think about the possibility of bundle-to-bundle re-entry since this is a readily Curr Probl Cardiol, May 2009 259 curable arrhythmia. These patients almost always have significant structural cardiac disease and the baseline ECG usually shows evidence of conduction system disease (bundle branch block pattern). The tachycardia form may look identical to the ECG inscribed during sinus rhythm (usually a left bundle branch block pattern) and thus mimic a supraventricular tachycardia with aberration. The tachycardia is often very rapid since it uses the conduction system and is poorly tolerated. Ablation of the right (or left) bundle branch is curative. Scar-related Right Ventricular Tachycardias Many disease processes can cause RV scars leading to VT, including idiopathic cardiomyopathies, genetic arrhythmogenic RV dysplasia, and sarcoidosis. The distinction between these diseases can be difficult, as the clinical manifestations can be similar. RV scars can also occur due to RV infarction and surgical repair of congenital heart disease, such as in patients with tetralogy of Fallot. Arrhythmogenic Right Ventricular Cardiomyopathy. Genetic arrhythmogenic right ventricular cardiomyopathy (ARVC) has been attributed to mutations in many proteins, most involved in cell-to-cell adhesion in desmosomes, such as plakoglobin and plakophillin.113,114 Areas of fibrofatty replacement of ventricular myocardium create the substrate for re-entry. VT and sudden death are the major clinical manifestations.115,116 Although involvement in the right ventricle is most commonly recognized, a substantial portion of patients have concomitant left ventricular involvement and predominant LV involvement has also been recognized. Ablation targets re-entry circuit regions in areas of scar using the methods described above. The scars are typically located near the tricuspid or pulmonic valve annuli. Focal origin VTs or epicardial re-entry with a focal endocardial breakthrough have also been described.117 Epicardial ablation is required in some cases. Verma and coworkers reported findings in 22 patients with recurrent and unstable VTs attributed to ARVC; 68% of patients had a family history of ARVC.118 Although the procedure was acutely successful in 82% of patients, VT recurred in 23, 27, and 47% of patients after 1, 2, and 3 years’ follow-up, respectively. In a multicenter registry, Dalal and colleagues also found a high recurrence rate of 75% at 14 months.119 These substantial recurrence rates may be due to disease progression. In contrast to the high recurrence rates observed in some studies, Marchlinski and coworkers120 found a better success rate of 89% for a series of 19 patients with RV scar-related VTs followed for 27 ⫾ 22 260 Curr Probl Cardiol, May 2009 months.120 Satomi and colleagues121 reported freedom from recurrent VT for 13 of 17 patients (76%) during a mean follow-up of 26 months.121 Based on these reports, it seems that scar-related VT reports include a somewhat heterogeneous group of patients, with genetic ARVC appearing to have a substantial risk of recurrences. Procedural risks appear to be low, but cardiac perforation and tamponade has been reported.95 Cardiac Sarcoidosis. Cardiac sarcoid is an important diagnostic consideration in nonischemic scar-related VT. Koplan and coworkers found cardiac sarcoid in 8% of patients with nonischemic forms of cardiomyopathy who were referred for catheter ablation.122 In more than half of those patients VT was the first manifestation of sarcoidosis. Scars were present in the right (100%) and the left (63%) ventricle. Ablation results were disappointing. Although ablation abolished 1 or more VT in 75% of patients, other VTs remained inducible in 88% of patients; more than 75% had recurrences of VT by 6 months.122 The role of ablation appears to be largely palliative in these patients. Postsurgical Scar-related VT involving RV regions of repair occur late after surgical correction of congenital heart disease, notably tetralogy of Fallot. Catheter ablation is feasible and can reduce recurrences, but in 1 small series only 43% of 14 patients with tetralogy of Fallot remained free of VT.123 Outcomes were better in a recent series of patients who had normal LV function and were continued on antiarrhythmic drug therapy during follow-up.124 Conclusions Catheter ablation is an important tool in the therapeutic arsenal for scar-related VT. The approach and outcomes are influenced by the underlying disease process. The use of newer tools and substrate mapping approaches now allow VTs that were formerly considered “unmappable” to be treated. Catheter ablation of epicardial VTs is now possible. Moreover, the field continues to benefit from technologic advancements. When expertise is available, catheter ablation should be increasingly considered for treatment of recurrent VT. Melvin M. Scheinman: The authors have provided us with a superb, very clearly written exposition on the total approach for ablation of scar-related VT. I believe that this contribution will be of immense value not only to the cardiac electrophysiology fellows but to general cardiologists interested in Curr Probl Cardiol, May 2009 261 the methods and results of ablation therapy. It is really interesting to reflect on the enormous changes that have evolved over the years relative to this important problem. The era of nonpharmacologic management of scarrelated VT actually started in the 1970s with a surgical approach that used endocardial mapping in the operating room. This was pioneered by Drs. Josephson, Miller, and Harken. In the mid 1980s ablative approaches using high-energy shock was introduced but this was associated with widespread barotrauma and was not precise enough for clinical use. The era of RF ablation as well as lessons learned about entrainment mapping (Drs. Waldo and Stevenson) allowed for a paradigm using entrainment mapping to located the VT isthmus as is elegantly described in the current text. The latest contributions include substrate mapping, use of 3D anatomic mapping, as well as use of epicardial ablative techniques. The progress in this field has been stunning and is very expertly described in text. Obviously, the final chapter has not been written since much more needs to be done to characterize and ablate these difficult myocardial circuits. REFERENCES 1. Maisel WH, Moynahan M, Zuckerman BD, et al. Pacemaker and ICD generator malfunctions: analysis of Food and Drug Administration annual reports. JAMA 2006;295:1901-6. 2. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med 2002;346:877-83. 3. Bardy GH, Lee KL, Mark DB, et al. Amiodarone or an implantable cardioverterdefibrillator for congestive heart failure. N Engl J Med 2005;352:225-37. 4. Connolly SJ, Dorian P, Roberts RS, 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;295:165-71. 5. Schron E, Exner DV, 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;105:589-94. 6. Credner SC, Klingenheben T, Mauss O, et al. Electrical storm in patients with transvenous implantable cardioverter-defibrillators: incidence, management and prognostic implications. J Am Coll Cardiol 1998;32:1909-15. 7. Moss AJ, Greenberg H, Case RB, et al. Long-term clinical course of patients after termination of ventricular tachyarrhythmia by an implanted defibrillator. Circulation 2004;110:3760-5. 8. Strickberger SA, Man KC, Daoud EG, et al. A prospective evaluation of catheter ablation of ventricular tachycardia as adjuvant therapy in patients with coronary artery disease and an implantable cardioverter-defibrillator. Circulation 1997;96: 1525-31. 9. European Heart Rhythm Association, Heart Rhythm Society: Zipes DP, Camm AJ, Borggrefe M, et al. ACC/AHA/ESC 2006 guidelines 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 and the European Society of Cardiology Committee for Practice guidelines (Writing 262 Curr Probl Cardiol, May 2009 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. Committee to Develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death). J Am Coll Cardiol 2006;48:e247-346. Haissaguerre M, Shoda M, Jais P, et al. Mapping and ablation of idiopathic ventricular fibrillation. Circulation 2002;106:962-7. Sarter BH, Finkle JK, Gerszten RE, et al. What is the risk of sudden cardiac death in patients presenting with hemodynamically stable sustained ventricular tachycardia after myocardial infarction? J Am Coll Cardiol 1996;28:122-9. el-Sherif N, Gough WB, Zeiler RH, et al. Reentrant ventricular arrhythmias in the late myocardial infarction period. 12. Spontaneous versus induced reentry and intramural versus epicardial circuits. J Am Coll Cardiol 1985;6:124-32. de Bakker JM, van Rijen HM. Continuous and discontinuous propagation in heart muscle. J Cardiovasc Electrophysiol 2006;17:567-73. Kleber AG, Rudy Y. Basic mechanisms of cardiac impulse propagation and associated arrhythmias. Physiol Rev 2004;84:431-88. Camelliti P, Green CR, Kohl P. Structural and functional coupling of cardiac myocytes and fibroblasts. Adv Cardiol 2006;42:132-49. Roelke M, Garan H, McGovern BA, et al. Analysis of the initiation of spontaneous monomorphic ventricular tachycardia by stored intracardiac electrograms. J Am Coll Cardiol 1994;23:117-22. Saeed M, Link MS, Mahapatra S, et al. Analysis of intracardiac electrograms showing monomorphic ventricular tachycardia in patients with implantable cardioverter-defibrillators. Am J Cardiol 2000;85:580-7. de Chillou C, Lacroix D, Klug D, et al. Isthmus characteristics of reentrant ventricular tachycardia after myocardial infarction. Circulation 2002;105:726-31. Stevenson WG, Friedman PL, Sager PT, et al. Exploring postinfarction reentrant ventricular tachycardia with entrainment mapping. J Am Coll Cardiol 1997; 29:1180-9. Bogun F, Knight B, Goyal R, et al. Discrete systolic potentials during ventricular tachycardia in patients with prior myocardial infarction. J Cardiovasc Electrophysiol 1999;10:364-9. Wellens HJ, Brugada P, Stevenson WG. Programmed electrical stimulation of the heart in patients with life-threatening ventricular arrhythmias: what is the significance of induced arrhythmias and what is the correct stimulation protocol? Circulation 1985;72:1-7. Bogun F, Kim HM, Han J, et al. Comparison of mapping criteria for hemodynamically tolerated, postinfarction ventricular tachycardia. Heart Rhythm 2006;3: 20-6. Buxton AE, Waxman HL, Marchlinski FE, et al. Role of triple extrastimuli during electrophysiologic study of patients with documented sustained ventricular tachyarrhythmias. Circulation 1984;69:532-40. Berruezo A, Mont L, Nava S, et al. Electrocardiographic recognition of the epicardial origin of ventricular tachycardias. Circulation 2004;109:1842-7. Josephson ME, Callans DJ. Using the twelve-lead electrocardiogram to localize the site of origin of ventricular tachycardia. Heart Rhythm 2005;2:443-6. Reddy VY, Malchano ZJ, Holmvang G, et al. Integration of cardiac magnetic resonance imaging with three-dimensional electroanatomic mapping to guide left Curr Probl Cardiol, May 2009 263 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 264 ventricular catheter manipulation: feasibility in a porcine model of healed myocardial infarction. J Am Coll Cardiol 2004;44:2202-13. Iwai S, Cantillon DJ, Kim RJ, et al. Right and left ventricular outflow tract tachycardias: evidence for a common electrophysiologic mechanism. J Cardiovasc Electrophysiol 2006;17:1052-8. Callans DJ, Ren JF, Michele J, et al. Electroanatomic left ventricular mapping in the porcine model of healed anterior myocardial infarction. Correlation with intracardiac echocardiography and pathological analysis. Circulation 1999;100: 1744-50. Marchlinski FE, Callans DJ, Gottlieb CD, Zado E. Linear ablation lesions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopathy. Circulation 2000;101:1288-96. Reddy VY, Neuzil P, Taborsky M, et al. Short-term results of substrate mapping and radiofrequency ablation of ischemic ventricular tachycardia using a salineirrigated catheter. J Am Coll Cardiol 2003;41:2228-36. Brunckhorst CB, Delacretaz E, Soejima K, et al. Impact of changing activation sequence on bipolar electrogram amplitude for voltage mapping of left ventricular infarcts causing ventricular tachycardia. J Interv Card Electrophysiol 2005;12: 137-41. Bogun F, Bender B, Li YG, et al. Analysis during sinus rhythm of critical sites in reentry circuits of postinfarction ventricular tachycardia. J Interv Card Electrophysiol 2002;7:95-103. Arenal A, Glez-Torrecilla E, Ortiz M, et al. Ablation of electrograms with an isolated, delayed component as treatment of unmappable monomorphic ventricular tachycardias in patients with structural heart disease. J Am Coll Cardiol 2003; 41:81-92. Bogun F, Good E, Reich S, et al. Isolated potentials during sinus rhythm and pace-mapping within scars as guides for ablation of post-infarction ventricular tachycardia. J Am Coll Cardiol 2006;47:2013-9. Harada T, Stevenson WG, Kocovic DZ, et al. Catheter ablation of ventricular tachycardia after myocardial infarction: relation of endocardial sinus rhythm late potentials to the reentry circuit. J Am Coll Cardiol 1997;30:1015-23. Arenal A, del Castillo S, Gonzalez-Torrecilla E, et al. Tachycardia-related channel in the scar tissue in patients with sustained monomorphic ventricular tachycardias: influence of the voltage scar definition. Circulation 2004;110:2568-74. Hsia HH, Lin D, Sauer WH, et al. Anatomic characterization of endocardial substrate for hemodynamically stable reentrant ventricular tachycardia: identification of endocardial conducting channels. Heart Rhythm 2006;3:503-12. Morady F, Kadish AH, DiCarlo L, et al. Long-term results of catheter ablation of idiopathic right ventricular tachycardia. Circulation 1990;82:2093-9. Brunckhorst CB, Delacretaz E, Soejima K, et al. Identification of the ventricular tachycardia isthmus after infarction by pace mapping. Circulation 2004;110:652-9. Harada T, Tomita Y, Nakagawa T, et al. Pace-mapping conduction delay at reentry circuit sites of ventricular tachycardia after myocardial infarction. Heart Vessels Suppl 1997;12:232-4. Brunckhorst CB, Stevenson WG, Soejima K, et al. Relationship of slow conduction detected by pace-mapping to ventricular tachycardia re-entry circuit sites after infarction. J Am Coll Cardiol 2003;41:802-9. Curr Probl Cardiol, May 2009 42. Waxman HL, Josephson ME. Ventricular activation during ventricular endocardial pacing. I. Electrocardiographic patterns related to the site of pacing. Am J Cardiol 1982;50:1-10. 43. Soejima K, Stevenson WG, Maisel WH, et al. Electrically unexcitable scar mapping based on pacing threshold for identification of the reentry circuit isthmus: feasibility for guiding ventricular tachycardia ablation. Circulation 2002;106: 1678-83. 44. Kadish AH, Schmaltz S, Morady F. A comparison of QRS complexes resulting from unipolar and bipolar pacing: implications for pace-mapping. Pacing Clin Electrophysiol 1991;14:823-32. 45. Gupta AK, Kumar AV, Lokhandwala YY, et al. Primary radiofrequency ablation for incessant idiopathic ventricular tachycardia. Pacing Clin Electrophysiol 2002; 25:1555-60. 46. Stevenson WG, Khan H, Sager P, et al. Identification of reentry circuit sites during catheter mapping and radiofrequency ablation of ventricular tachycardia late after myocardial infarction. Circulation 1993;88:1647-70. 47. Fitzgerald DM, Friday KJ, Wah J, et al. Electrogram patterns predicting successful catheter ablation of ventricular tachycardia. Circulation 1988;77:806-14. 48. Bogun F, Bahu M, Knight BP, et al. Comparison of effective and ineffective target sites that demonstrate concealed entrainment in patients with coronary artery disease undergoing radiofrequency ablation of ventricular tachycardia. Circulation 1997;95:183-90. 49. Kocovic DZ, Harada T, Friedman PL, et al. Characteristics of electrograms recorded at reentry circuit sites and bystanders during ventricular tachycardia after myocardial infarction. J Am Coll Cardiol 1999;34:381-8. 50. Tung S, Soejima K, Maisel WH, et al. Recognition of far-field electrograms during entrainment mapping of ventricular tachycardia. J Am Coll Cardiol 2003;42:110-5. 51. Strickberger SA, Knight BP, Michaud GF, et al. Mapping and ablation of ventricular tachycardia guided by virtual electrograms using a noncontact, computerized mapping system. J Am Coll Cardiol 2000;35:414-21. 52. Della Bella P, Pappalardo A, Riva S, et al. Non-contact mapping to guide catheter ablation of untolerated ventricular tachycardia. Eur Heart J 2002;23:742-52. 53. Schilling RJ, Peters NS, Davies DW. Feasibility of a noncontact catheter for endocardial mapping of human ventricular tachycardia. Circulation 1999;99: 2543-52. 54. Waldo AL. From bedside to bench: entrainment and other stories. Heart Rhythm 2004;1:94-106. 55. Stevenson WG, Sager PT, Friedman PL. Entrainment techniques for mapping atrial and ventricular tachycardias. J Cardiovasc Electrophysiol 1995;6:201-16. 56. Fei H, Hanna MS, Frame LH. Assessing the excitable gap in reentry by resetting. Implications for tachycardia termination by premature stimuli and antiarrhythmic drugs. Circulation 1996;94:2268-77. 57. Hadjis TA, Harada T, Stevenson WG, et al. Effect of recording site on postpacing interval measurement during catheter mapping and entrainment of postinfarction ventricular tachycardia. J Cardiovasc Electrophysiol 1997;8:398-404. 58. de Bakker JM, van Capelle FJ, Janse MJ, et al. Fractionated electrograms in dilated cardiomyopathy: origin and relation to abnormal conduction. J Am Coll Cardiol 1996;27:1071-8. Curr Probl Cardiol, May 2009 265 59. Soejima K, Stevenson WG, Maisel WH, et al. The N ⫹ 1 difference: A new measure for entrainment mapping. J Am Coll Cardiol 2001;37:1386-94. 60. Fontaine G, Frank R, Tonet J, Grosgogeat Y. Identification of a zone of slow conduction appropriate for VT ablation: theoretical and practical considerations. Pacing Clin Electrophysiol 1989;12:262-7. 61. Morady F, Kadish A, Rosenheck S, et al. Concealed entrainment as a guide for catheter ablation of ventricular tachycardia in patients with prior myocardial infarction. J Am Coll Cardiol 1991;17:678-89. 62. Ormaetxe JM, Almendral J, Martinez-Alday JD, et al. Analysis of the degree of QRS fusion necessary for its visual detection: importance for the recognition of transient entrainment. Circulation 1997;96:3509-16. 63. Ellison KE, Stevenson WG, Sweeney MO, et al. Catheter ablation for hemodynamically unstable monomorphic ventricular tachycardia. J Cardiovasc Electrophysiol 2000;11:41-4. 64. Soejima K, Suzuki M, Maisel WH, et al. Catheter ablation in patients with multiple and unstable ventricular tachycardias after myocardial infarction: short ablation lines guided by reentry circuit isthmuses and sinus rhythm mapping. Circulation 2001;104:664-9. 65. Hadjis TA, Stevenson WG, Harada T, et al. Preferential locations for critical reentry circuit sites causing ventricular tachycardia after inferior wall myocardial infarction. J Cardiovasc Electrophysiol 1997;8:363-70. 66. Wilber DJ, Kopp DE, Glascock DN, et al. Catheter ablation of the mitral isthmus for ventricular tachycardia associated with inferior infarction. Circulation 1995;92: 3481-9. 67. Volkmer M, Ouyang F, Deger F, et al. Substrate mapping vs. tachycardia mapping using CARTO in patients with coronary artery disease and ventricular tachycardia: impact on outcome of catheter ablation. Europace 2006;8:968-76. 68. Delacretaz E, Stevenson WG. Catheter ablation of ventricular tachycardia in patients with coronary heart disease. Part I: mapping. Pacing Clin Electrophysiol 2001;24:1261-77. 69. Delacretaz E, Soejima K, Brunckhorst CB, et al. Assessment of radiofrequency ablation effect from unipolar pacing threshold. Pacing Clin Electrophysiol 2003; 26:1993-6. 70. Delacretaz E, Stevenson WG, Winters GL, et al. Ablation of ventricular tachycardia with a saline-cooled radiofrequency catheter: anatomic and histologic characteristics of the lesions in humans. J Cardiovasc Electrophysiol 1999;10:860-5. 71. Bartlett TG, Mitchell R, Friedman PL, et al. Histologic evolution of radiofrequency lesions in an old human myocardial infarct causing ventricular tachycardia. J Cardiovasc Electrophysiol 1995;6:625-9. 72. Soejima K, Delacretaz E, Suzuki M, et al. Saline-cooled versus standard radiofrequency catheter ablation for infarct-related ventricular tachycardias. Circulation 2001;103:1858-62. 73. Cooper JM, Sapp JL, Tedrow U, et al. Ablation with an internally irrigated radiofrequency catheter: learning how to avoid steam pops. Heart Rhythm 2004; 1:329-33. 266 Curr Probl Cardiol, May 2009 74. Yokoyama K, Nakagawa H, Wittkampf FH, et al. Comparison of electrode cooling between internal and open irrigation in radiofrequency ablation lesion depth and incidence of thrombus and steam pop. Circulation 2006;113:11-9. 75. Matsudaira K, Nakagawa H, Wittkampf FH, et al. High incidence of thrombus formation without impedance rise during radiofrequency ablation using electrode temperature control. Pacing Clin Electrophysiol 2003;26:1227-37. 76. Brugada J, Berruezo A, Cuesta A, et al. Nonsurgical transthoracic epicardial radiofrequency ablation: an alternative in incessant ventricular tachycardia. J Am Coll Cardiol 2003;41:2036-43. 77. Soejima K, Stevenson WG, Sapp JL, et al. Endocardial and epicardial radiofrequency ablation of ventricular tachycardia associated with dilated cardiomyopathy: the importance of low-voltage scars. J Am Coll Cardiol 2004;43:1834-42. 78. Sosa E, Scanavacca M, d’Avila A, et al. Nonsurgical transthoracic epicardial catheter ablation to treat recurrent ventricular tachycardia occurring late after myocardial infarction. J Am Coll Cardiol 2000;35:1442-9. 79. Daniels DV, Lu YY, Morton JB, et al. Idiopathic epicardial left ventricular tachycardia originating remote from the sinus of Valsalva: electrophysiological characteristics, catheter ablation, and identification from the 12-lead electrocardiogram. Circulation 2006;113:1659-66. 80. Soejima K, Couper G, Cooper JM, et al. Subxiphoid surgical approach for epicardial catheter-based mapping and ablation in patients with prior cardiac surgery or difficult pericardial access. Circulation 2004;110:1197-201. 81. d’Avila A, Houghtaling C, Gutierrez P, et al. ME Josephson, et al. Catheter ablation of ventricular epicardial tissue: a comparison of standard and cooled-tip radiofrequency energy. Circulation 2004;109:2363-9. 82. Lustgarten DL, Bell S, Hardin N, et al. Safety and efficacy of epicardial cryoablation in a canine model. Heart Rhythm 2005;2:82-90. 83. D’avila A, Gutierrez P, Scanavacca M, et al. Effects of radiofrequency pulses delivered in the vicinity of the coronary arteries: implications for nonsurgical transthoracic epicardial catheter ablation to treat ventricular tachycardia. Pacing Clin Electrophysiol 2002;25:1488-95. 84. Sapp JL, Cooper JM, Zei P, et al. Large radiofrequency ablation lesions can be created with a retractable infusion-needle catheter. J Cardiovasc Electrophysiol 2006;17:657-61. 85. Thiagalingam A, Pouliopoulos J, Barry M, et al. Cooled needle catheter ablation creates deeper and wider lesions than irrigated tip catheter ablation. J Cardiovasc Electrophysiol 2005;16:508-15. 86. Kay GN, Epstein AE, Bubien RS, et al. Intracoronary ethanol ablation for the treatment of recurrent sustained ventricular tachycardia. J Am Coll Cardiol 1992; 19:159-68. 87. Sacher F, Sobieszczyk P, Tedrow U, et al. Transcoronary ethanol ventricular tachycardia ablation in the modern electrophysiology Era. Heart Rhythm (in press). 88. Aryana A, d’Avila A, Heist EK, et al. Remote magnetic navigation to guide endocardial and epicardial catheter mapping of scar-related ventricular tachycardia. Circulation 2007;115:1191-200. Curr Probl Cardiol, May 2009 267 89. Burkhardt JD, Saliba WI, Schweikert RA, et al. Remote magnetic navigation to map and ablate left coronary cusp ventricular tachycardia. J Cardiovasc Electrophysiol 2006;17:1142-4. 90. Friedman P, Munger TM, Torres N, et al. Percutaneous endocardial and epicardial ablation of hypotensive ventricular tachycardia with percutaneous left ventricular assist in the electrophysiology laboratory. J Cardiovasc Electrophysiol 2007;18: 106-9. 91. Calkins H, Epstein A, Packer D, et al. Catheter ablation of ventricular tachycardia in patients with structural heart disease using cooled radiofrequency energy: results of a prospective multicenter study. Cooled RF Multi Center Investigators Group. J Am Coll Cardiol 2000;35:1905-14. 92. Wilber DJ, Stevenson WG, Nakagawa H, et al. Catheter ablation for patients with mappable versus unmappable VT late after myocardial infarction. Heart Rhythm 2005;2:S119. 93. Marchlinski FE, Zado ES, Callans DJ, et al. Hybrid therapy for ventricular arrhythmia management. Cardiol Clin 2000;18:391-406. 94. Scheinman MM, Huang S. The 1998 NASPE prospective catheter ablation registry. Pacing Clin Electrophysiol 2000;23:1020-8. 95. Borger van der Burg AE, de Groot NM, van Erven L, et al. Long-term follow-up after radiofrequency catheter ablation of ventricular tachycardia: A successful approach? J Cardiovasc Electrophysiol 2002;13:417-23. 96. Segal OR, Chow AW, Markides V, et al. Long-term results after ablation of infarct-related ventricular tachycardia. Heart Rhythm 2005;2:474-82. 97. El-Shalakany A, Hadjis T, Papageorgiou P, et al. Entrainment/mapping criteria for the prediction of termination of ventricular tachycardia by single radiofrequency lesion in patients with coronary artery disease. Circulation 1999;99:2283-9. 98. Della Bella P, Riva S, Fassini G, et al. Incidence and significance of pleomorphism in patients with postmyocardial infarction ventricular tachycardia. Acute and long-term outcome of radiofrequency catheter ablation. Eur Heart J 2004;25: 1127-38. 99. O’Donnell D, Bourke JP, Furniss SS. Standardized stimulation protocol to predict the long-term success of radiofrequency ablation of postinfarction ventricular tachycardia. Pacing Clin Electrophysiol 2003;26:348-51. 100. Deneke T, Grewe PH, Lawo T, et al. Substrate-modification using electroanatomical mapping in sinus rhythm to treat ventricular tachycardia in patients with ischemic cardiomyopathy. Z Kardiol 2005;94:453-60. 101. Kautzner J, Cihak R, Peichl P, et al. Catheter ablation of ventricular tachycardia following myocardial infarction using three-dimensional electroanatomical mapping. Pacing Clin Electrophysiol 2003;26:342-7. 102. Stevenson WG, Wilber DJ, Natale A, et al. Irrigated radiofrequency catheter ablation guided by electroanatomic mapping for recurrent ventricular tachycardia after myocardial infarction: the multicenter thermocool ventricular tachycardia ablation trial. Circulation 2008;118:2773-82. 103. Della Bella P, De Ponti R, Uriarte J, et al. Catheter ablation and antiarrhythmic drugs for haemodynamically tolerated post-infarction ventricular tachycardia; long-term outcome in relation to acute electrophysiological findings. Eur Heart J 2002;23:414-24. 268 Curr Probl Cardiol, May 2009 104. Sra J, Bhatia A, Dhala A, et al. Electroanatomically guided catheter ablation of ventricular tachycardias causing multiple defibrillator shocks. Pacing Clin Electrophysiol 2001;24:1645-52. 105. Stevenson WG, Soejima K. Catheter ablation for ventricular tachycardia. Circulation 2007;115:2750-60. 106. Cesario DA, Vaseghi M, Boyle NG, et al. Value of high-density endocardial and epicardial mapping for catheter ablation of hemodynamically unstable ventricular tachycardia. Heart Rhythm 2006;3:1-10. 107. Delacretaz E, Stevenson WG, Ellison KE, et al. Mapping and radiofrequency catheter ablation of the three types of sustained monomorphic ventricular tachycardia in nonischemic heart disease. J Cardiovasc Electrophysiol 2000;11:11-7. 108. Hsia HH, Callans DJ, Marchlinski FE. Characterization of endocardial electrophysiological substrate in patients with nonischemic cardiomyopathy and monomorphic ventricular tachycardia. Circulation 2003;108:704-10. 109. Nazarian S, Bluemke DA, Lardo AC, et al. Magnetic resonance assessment of the substrate for inducible ventricular tachycardia in nonischemic cardiomyopathy. Circulation 2005;112:2821-5. 110. Blanck Z, Dhala A, Deshpande S, et al. Bundle branch reentrant ventricular tachycardia: Cumulative experience in 48 patients. J Cardiovasc Electrophysiol 1993;4:253-62. 111. Lopera G, Stevenson WG, Soejima K, et al. Identification and ablation of three types of ventricular tachycardia involving the his-Purkinje system in patients with heart disease. J Cardiovasc Electrophysiol 2004;15:52-8. 112. Bogun F, Good E, Reich S, et al. Role of Purkinje fibers in post-infarction ventricular tachycardia. J Am Coll Cardiol 2006;48:2500-7. 113. Calkins H. Arrhythmogenic right-ventricular dysplasia/cardiomyopathy. Curr Opin Cardiol 2006;21:55-63. 114. Sen-Chowdhry S, Syrris P, Ward D, et al. Clinical and genetic characterization of families with arrhythmogenic right ventricular dysplasia/cardiomyopathy provides novel insights into patterns of disease expression. Circulation 2007;115:1710-20. 115. Dalal D, Nasir K, Bomma C, et al. Arrhythmogenic right ventricular dysplasia: a US experience. Circulation 2005;112:3823-32. 116. Hulot JS, Jouven X, Empana JP, et al. Natural history and risk stratification of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circulation 2004;110: 1879-84. 117. Miljoen H, State S, de Chillou C, et al. Electroanatomic mapping characteristics of ventricular tachycardia in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia. Europace 2005;7:516-24. 118. Verma A, Kilicaslan F, Schweikert RA, et al. Short- and long-term success of substrate-based mapping and ablation of ventricular tachycardia in arrhythmogenic right ventricular dysplasia. Circulation 2005;111:3209-16. 119. Dalal D, Jain R, Tandri H, et al. Long-term efficacy of catheter ablation of ventricular tachycardia in patients with arrhythmogenic right ventricular dysplasia/ cardiomyopathy. J Am Coll Cardiol 2007;50:432-40. 120. Marchlinski FE, Zado E, Dixit S, et al. Electroanatomic substrate and outcome of catheter ablative therapy for ventricular tachycardia in setting of right ventricular cardiomyopathy. Circulation 2004;110:2293-8. 121. Satomi K, Kurita T, Suyama K, et al. Catheter ablation of stable and unstable Curr Probl Cardiol, May 2009 269 ventricular tachycardias in patients with arrhythmogenic right ventricular dysplasia. J Cardiovasc Electrophysiol 2006;17:469-76. 122. Koplan BA, Soejima K, Baughman K, et al. Refractory ventricular tachycardia secondary to cardiac sarcoid: electrophysiologic characteristics, mapping, and ablation. Heart Rhythm 2006;3:924-9. 123. Morwood JG, Triedman JK, Berul CI, et al. Radiofrequency catheter ablation of ventricular tachycardia in children and young adults with congenital heart disease. Heart Rhythm 2004;1:301-8. 124. Furushima H, Chinushi M, Sugiura H, et al. Ventricular tachycardia late after repair of congenital heart disease: efficacy of combination therapy with radiofrequency catheter ablation and class III antiarrhythmic agents and long-term outcome. J Electrocardiol 2006;39:219-24. 270 Curr Probl Cardiol, May 2009