Patients with structural heart disease are at risk of ventricular tachycardia (VT), a major cause of sudden cardiac death (SCD) with an incidence of one to two per 1,000 per year.1 The proven life-saving benefit achieved with implantable cardioverter–defibrillators (ICDs) is due to the reduction in SCD. However, several considerations support an important role for therapies that prevent episodes of VT. First, ICDs do not prevent VT, and after a single episode of VT or ventricular fibrillation (VF), 33–69% of patients receive at least one appropriate ICD therapy within two years.2,3 In patients in whom an ICD has been implanted for primary prevention of SCD, a first episode of VT/VF occurs in 35% within three years, with a 55% risk of subsequent device therapies.4 Second, a significant number of tachycardia terminations necessitate shocks, which have an important impact on quality of life.5 In addition to this, in patients with heart failure due to ischaemic and non-ischaemic cardiomyopathy (NICM) ICD shocks might be harmful. Two or more appropriate shocks were associated with an eight-fold increased risk of death compared with patients without shocks.6 Whether episodes of VT and ICD shocks directly contribute to adverse outcome or are a marker of disease severity or progression is a matter of debate. Both factors probably play a role.7 Third, ICD trials for secondary prevention of SCD have excluded patients with haemodynamically tolerated VT. Information on the clinical outcome of these patients is therefore limited. Finally, ICDs do not reduce mortality compared with drug therapy in patients with relatively preserved ventricular function.8,9 Despite this, antiarrhythmic drug therapy has disappointing efficacy and adverse drug effects. These led to the discontinuation of amiodarone and sotalol in 18.2 and 23.5% of patients, respectively, after one year in the Optimal Pharmacological Therapy in Cardioverter Defibrillator Patients (OPTIC) trial.10
Since the introduction of radiofrequency catheter ablation (RFCA) in 1987, the safety and efficacy of the treatment for VT in the presence and absence of structural heart disease have been evaluated. In patients without structural heart disease, RFCA for monomorphic VT is curative and safe in the majority of patients and is now considered to be a first-line therapy in highly symptomatic patients.11 The most common type of VT originates from the outflow tracts. Focal ablation targeting the earliest site of activation is successful in the long term in >85% of patients.12
By contrast, in patients with structural heart disease the safety and efficacy of the procedure, appropriate patient selection, optimal timing and the best end-point are still controversial. Considerations of risks and benefits often depend on individual patient factors and the experience of the operator.
The Substrate for Scar-related Ventricular Tachycardia
The underlying mechanism of most VT in patients with structural heart disease is re-entry involving areas of ventricular scar. Areas of dense fibrosis and other areas of unexcitable tissue, such as the valve annuli, form regions of conduction block that define re-entry circuit borders and create intervening isthmuses, also referred to as channels, of surviving myocardial bundles.13–15 Fibrosis between surviving myocyte bundles functionally prolongs the pathway for impulse propagation, creating slow conduction through the scar.13 Inhomogeneous scar areas occur after myocardial infarction (MI), when a wave of cell death begins in the subendocardial myocardium and progresses towards the subepicardial myocardium, usually confined to a territory supplied by a coronary artery. Scar tissue can also occur in NICM.
Ventricular Tachycardia Ablation in Ischaemic Cardiomyopathy
Most of the data on VT ablation are derived from post-MI patients. Initially, VTs considered for ablation were drug-refractory, monomorphic, haemodynamically tolerated and reproducibly inducible in the electrophysiology lab. These pre-conditions allow for mapping during VT such that the activation sequence can be defined from point-by-point mapping. The critical isthmus can be confirmed by entrainment mapping and is the target for focal ablation (see Figure 1).
Single-centre-reported acute success rates are 71–86%, with VT recurrence rates of 26–43% over a follow-up of 13–41 months.16–20 However, in patients in whom ablation fails to eliminate the index VT or in whom another VT is inducible, the three- to four-year risk of VT recurrence was much higher (60–64%) compared with patients with no inducible monomorphic VT at the end of the procedure (14–20%).16,20
Even in stable VT, the absence of an adequate target on the endocardium where catheter ablation can interrupt re-entry is a major cause of ablation failure. Circuits located deep within the septum or subepicardially might not be accessible by standard radiofrequency (RF) applications. Compared with standard RF, cooled or irrigated RF ablation has proved more effective for terminating scar-related VT due to the formation of larger and deeper lesions, and is now preferred for ablation of scar-related VT.21
In 2000, the safety and efficacy of catheter ablation using an internal irrigation catheter was evaluated in the first prospective multicentre study on catheter ablation of VT performed in 143 patients with structural heart disease, the majority being post-MI patients.22 Patients with ≥2 episodes of stable, drug-refractory VTs were included, allowing for activation and entrainment mapping. In 106 patients (75%), all mappable VTs were successfully ablated; in 59 patients (41%) no VT could be induced after a complete induction protocol at the end of the procedure.22 Twelve patients (8%) experienced major complications, including four (2.7%) deaths. The one-year recurrence rate was 56%; however, a ≥75% reduction in the VT frequency was observed in 81% of patients. Of interest, 40% of the patients had also inducible fast VTs (cycle length <300ms) that were not targeted.22
The Need for Substrate-based Ablation
Currently, fewer than 30% of patients referred for RFCA of VT are suitable for ablation guided only by mapping during VT. The majority of patients (60–80%) have unstable VTs due to haemodynamic intolerance or poor reproducibility.23,24 In addition, multiple morphologies of VT are often inducible and VT data might only be available from ICD interrogation, preventing identification of clinical VT.23 These challenges have led to a shift away from targeting single, mappable VTs to a substrate-based approach that targets broader regions containing the likely substrate causing VT without the need for mapping during VT. These substrate-based approaches have been facilitated by the use of 3D electroanatomical mapping systems. The reduction of myocytes in regions of scar tissue reduces the local amplitude of recorded electrograms, allowing areas of scar to be identified from the peak-to-peak electrogram voltage. In animal models and humans, infarct regions typically have a bipolar electrogram amplitude of <1.5mV.24–26 These low-voltage areas can be displayed in 3D anatomical maps by colour-coding the peak-to-peak electrogram amplitude, referred to as voltage maps (see Figures 1B and 2).
After MI, scar areas are generally large, ranging in size from 30 to 110cm2.23,24 Ablation of the entire area or its circumference is usually not practical. Additional criteria to subselect regions of the scar for ablation aim to identify potential channels or isthmuses within the scar during sinus rhythm. Small single-centre studies have reported favourable results applying different criteria.27–29
Dense fibrosis as a potential channel barrier can be identified by non-capture during high-output pacing within low-voltage areas and is referred to as electrical unexcitable scar. This unexcitable scar formed at least one border of 20 VT re-entry circuits in 14 patients validated by entrainment or pace mapping.27
Based on the hypothesis that conducting channels within dense fibrosis should have larger voltage amplitudes than the surrounding non-conducting areas, adjustment of voltage criteria for dense scar to ≤0.2mV allowed for the identification of potential channels in 20 patients. Ablation in these channels abolished 88% of inducible VTs and 77% of patients remained free of VT during follow-up.28
Potential channels and areas of slow conduction can also be detected from isolated late potentials, inscribed after the end of the QRS during sinus rhythm (see Figure 1B). Targeting these areas in 18 patients with unmappable VTs abolished all inducible VTs in 13 out of 18 patients. During follow-up (9±4 months), 72% of the patients had no recurrence.29
During pace-mapping, a delay of >40ms between the stimulus and QRS onset is consistent with slow conduction away from the pacing site. A paced QRS that matches the VT with a long stimulus-QRS delay is consistent with pacing in a potential re-entry circuit isthmus.23,30 Once a potential channel is identified, RF lesions can be placed, usually parallel to the infarct border, in the electroanatomical border zone (see Figure 1E).
In small single-centre studies including nine to 40 post-MI patients, the majority of whom were ICD recipients with frequent VT episodes, all inducible VTs were targeted. Linear lesions were applied, guided by the above-described additional criteria to identify ablation target areas.23,24,31,32 Non-inducibility of all monomorphic VTs was achieved in 46–79% of patients.
The lowest acute success rate (33%) was reported in a subgroup of patients in whom no VT-related isthmus could be identified. During a mean follow-up of three to 15 months, recurrence rates ranged between 17–50% and were higher if VT was still inducible (67 versus 27%) or if a VT isthmus could not be identified (53 versus 28%).23,32 In none of these studies was a major complication reported.
Two recently conducted multicentre studies, the Euro-VT-Study (63 patients from eight centres) and the Multicenter Thermocool Ventricular Tachycardia Ablation Trial (231 patients from 18 centres) may best reflect the current status and outcome of VT ablation in post-MI patients.33,34 Both trials enrolled patients with recurrent or incessant VT for ablation with open irrigated tip catheters using substrate and/or entrainment mapping facilitated by a 3D electroanatomical mapping system. Patients had a mean of 3±2 inducible VTs and unmappable VTs were present in 63 and 69% of patients, respectively.33,34
In the European study33 acute success, defined as termination and non-inducibility of all clinically-relevant VTs, was achieved in 51 patients (81%). During the following six months, 31 patients (49%) had recurrent VT. In 79% of patients with VT recurrence, a significant reduction in device therapies was observed.
In the Thermocool study,34 ablation abolished at least one VT in 81% of patients; in 51% at least one monomorphic VT remained inducible. During the six-month follow-up period, 51% had recurrent VT; however, 67% of the 142 patients with VT recurrence had a >75% reduction in frequency of VT episodes.
In the Euro-VT study there was no procedure-related mortality. Five per cent had minor complications.34 In the Thermocool study, procedural mortality was 3%; however, six of the seven deaths were related to uncontrollable VT, which might be the inevitable consequence of a failed procedure. Seven per cent of the patients experienced non-fatal complications.33 No strokes or other thromboembolic events occurred in either study.33,34 Thus, catheter ablation is a safe and effective option to reduce VT episodes and thereby ICD interventions in post-MI patients. However, follow-up was short in all trials, and the effect of concomitant drug therapy was not systematically evaluated.
Epicardial Ablation in Post-myocardial Infarction Patients
Although a critical portion of the VT circuit after MI usually involves the endocardial layer of the left ventricle, in a substantial number the complete re-entry circuit or significant portions of the circuit may be located in the subepicardium. This is more common with inferior than anterior wall infarctions.35–38 Epicardial mapping and ablation using a transcutaneous puncture to enter the pericardial space was pioneered by Sosa and co-workers in patients with Chagas disease39 and has been extrapolated to other populations.
In a large observational multicentre series, epicardial ablation was performed in only 20 (7%) of 278 ablation procedures for post-MI VT.40 However, of the 213 patients with ischaemic cardiomyopathy, 108 (51%) had prior coronary artery bypass surgery. Adhesions after surgery might exclude percutaneous pericardial access or limit sufficient mapping, even when access is facilitated by a surgical window.41,42 Despite a potential subepicardial substrate, careful patient selection is therefore mandatory.
Electrical storm (ES), characterised by very frequent arrhythmic episodes resulting in appropriate ICD shocks, is a frightening event that can cause sudden death and is associated with a poor long-term prognosis.43 In the absence of a reversible cause, catheter ablation can abolish the ES, either by targeting the trigger if polymorphic VT and VF are initiated by monomorphic premature ventricular contractions or by substrate-modification strategies.44,45 A recent single-centre study reported on 95 patients, the majority with coronary artery disease who presented with 14±8 ICD shocks per day. After catheter ablation targeting all inducible VTs, the ES was acutely suppressed in all patients and 85 (89%) were non-inducible for clinical VT. In non-inducible patients, no ES recurred and cardiac mortality was significantly lower compared with patients in whom clinical VT remained inducible.46
Early Use of Catheter Ablation
Although recent ACC/AHA/ESC guidelines state that RFCA is indicated as a palliative and adjunctive therapy to ICD implantation in patients who present with drug-refractory incessant VT or ES or in patients who receive multiple ICD shocks, there might be a role for catheter ablation in early intervention.47
The Substrate Mapping and Ablation in Sinus Rhythm to Halt Ventricular Tachycardia (SMASH-VT) trial included 128 post-MI patients who had undergone a planned or a recent ICD implantation for ventricular fibrillation, haemodynamically unstable VT or syncope with inducible VT during EP. The patients were randomised to ICD alone or ICD and adjunctive catheter ablation using a substrate-based approach.2 After two years of follow-up, eight patients in the ablation group (12%) and 21 (33%) in the control group had received at least one episode of appropriate ICD therapy. Catheter ablation led to a 73% reduction in ICD shocks. Of interest, there was a trend towards reduced mortality in the ablation group (9 versus 17%; p=0.29). Although there were no procedure-related deaths, 4.7% of the patients experienced a non-fatal ablation-related complication.2
The multicentre Ventricular Tachycardia Ablation in Addition to Implantable Defibrillators in Coronary Heart Disease (VTACH) trial randomised 107 post-MI patients who presented with a first episode of stable VT to ICD alone or ICD and catheter ablation.3 In the ablation group, the median time to first VT/VF was significantly prolonged (5.9 versus 18.6 months) and the median number of appropriate ICD interventions was reduced by 93% per patient per year of follow-up.3 Despite this, the VTACH trial results did not translate into an improvement of quality of life. After two years of follow-up, 53% of patients in the ablation group and 71% of controls had at least one VT or VF episode.3 In patients with a left ventricular ejection fraction of ≤30%, survival free from VT or VF did not differ between groups. There were no procedure-related deaths, but non-fatal complications occurred in 3.8% of patients, including one transient cerebral ischaemic event.3 Early use of ablation can be considered in selected patients who receive an ICD as an alternative to drug therapy, provided that the procedure can be performed safely in a highly experienced centre.
Substrate for Ventricular Tachycardia in the Reperfusion Era
Much of the understanding of the VT substrate in healed infarction is based on animal models of a chronic occluded artery with dense scars and on intaoperative mapping studies, typically performed in patients with aneurysm formation.26,36 Early reperfusion – which has become the standard treatment for acute MI – seems to be associated with less dense and less confluent histological and electroanatomical scars that appear to give rise to faster spontaneous and inducible VT.48
The larger border zone in reperfused patients with only small areas of dense scar may require a different substrate mapping approach (see Figure 2). Whether a more ‘patchy’ pattern of electroanatomical scar after reperfusion will pose a challenge in substrate-based mapping and ablation needs further evaluation.
Substrate for Ventricular Tachycardia in Non-ischaemic Cardiomyopathy
Sustained monomorphic VT occurs, although less frequently in those with NICM, in 80% of patients due to myocardial re-entry, with the remainder due to bundle branch re-entry or a focal origin.49 However, there may be important differences between post-MI scars and scars in NICM. In addition, NICM represents the clinical presentation of various aetiologies, such as idiopathic dilated cardiomyopathy, post-viral perimyocarditis, toxin-associated cardiomyopathy, sarcoidosis and others, that might influence scar characteristics and distribution. Location and extent of scar is less predictable and might have a predilection for the midmyocardium or subepicardium.
Endocardial bipolar voltage mapping performed in patients who present with VT in the context of NICM revealed an only modest distribution of abnormal electrograms, usually involving <25% of the total endocardial surface.49–52 In those patients who underwent epicardial voltage mapping, the electroanatomical scar tends to be larger on the epicardial surface with a basal left ventricular (LV) predilection, often in the inferolateral LV-free wall (see Figure 3).49,51,52
Data on catheter ablation of VT in NICM are from small single-centre studies performed in highly symptomatic patients after drug failure. Large multicentre studies are lacking.
Endocardial ablation seems to be associated with lower success rates (27–74%) compared with post-MI patients; however, after endocardial ablation failure, epicardial ablation can be effective.49,51 Eighteen of 22 patients who underwent endo- and epicardial substrate mapping and ablation after prior endocardial ablation failure were rendered non-inducible at the end of the procedure, with favourable long-term results (29% recurrence during 18±7 months of follow-up). In one patient the procedure was aborted due to hypotension after tamponade.51 The majority of patients had multiple and unstable VT requiring a substrate-based ablation approach.
Late potentials, which are likely to reflect areas of slow conduction in a fixed substrate, have been used to guide ablation. However, compared with post-MI patients, these potentials were observed less frequently in one series comparing 16 NICM patients with 17 post-MI patients.52 A substrate-based approach including ablation of late potential was acutely effective in 82% of post-MI patients and only 44% of patients with NICM. VT recurred in 18% of post-MI and 50% of NICM patients after a follow-up of 12±10 and 15±13 months respectively.52 These data suggest that the VT substrate differs between NICM and post-MI and that in some patients functional areas of block, rather than a fixed anatomical substrate, might play an important role.
Scar-related Right Ventricular Tachycardia
Scar-related right VTs are infrequent, and arrhythmogenic right ventricular cardiomyopathy (ARVC) is the most commonly described cause in single-centre studies reporting on the outcome of VT ablation. ARVC is a progressive, often inherited cardiomyopathy, characterised by loss of right ventricular myocytes, with replacement of fibro-fatty tissue beginning in the subepicardium and progressing to the subendocardium.
Before the widespread use of electroanatomical mapping systems, ablation sites were predominately guided by conventional mapping techniques. Two series including 24 and 29 patients reported acute success rates, defined as non-inducibility of any VT, of 46 and 45%, respectively.53,54 After two years of follow-up, high recurrence rates after a single procedure of 75 and 41% were found. One procedure-related death was reported.53,54
As in post-MI VT, the concept of substrate mapping and ablation facilitated by a 3D mapping system has evolved over time, including the application of linear lesions to encircle low-voltage areas and connect scars during stable rhythm. This strategy seems to translate into better acute outcome. In three reported series, acute success was similar and achieved in 79–88% of the patients.55–57 There was one acute pericardial tamponade requiring drainage.56 Despite the success rates, recurrence rates differed substantially during follow-up. In two series, VT recurred in 24% and 12% of patients during a mean follow-up of 26±15 months and 27±22 months, respectively.55,57 In one series the recurrence rate reached 47% after a three-year follow-up.56
The variable outcome in these small series might reflect progression of the disease and perhaps inclusion of patients with post-inflammatory myopathy or sarcoidosis, which can mimic ARVD.58,59 In the latter study, ablation results were disappointing. Although ablation abolished at least one VT in 75% of the patients, in one small series the majority remained inducible (88%) and more than 75% had recurrence during short-term follow-up.59
An autopsy series of ARVD patients has identified a more extensive epicardial involvement.60 Accordingly, systematically-performed endocardial and epicardial mapping after endocardial ablation failure could demonstrate that the electroanatomical substrate was significantly larger on the epicardium. In addition, certain VT electrocardiography (ECG) characteristics seem to predict an epicardial exit. A combined endocardial and epicardial ablation rendered 85% of 13 patients uninducible. During follow-up (18.3±12.7 months), 77% of patients were free of VT recurrence.61
Indications, Complications and Limitations of an Epicardial Approach
The chance of needing an epicardial approach in patients with ischaemic and NICM cannot be reliably predicted based on the pre-procedural data available. Although likely overestimated because of the referral nature, the highest prevalence of epicardial VT was reported in patients with ARVC (41%), followed by NICM (35%).41 In addition, certain VT echocardiography morphology characteristics seem to predict an epicardial exit.62–64
The efficacy of epicardial ablation after failed endocardial ablation in selected patients is encouraging; however, the data are derived from highly experienced centres and may not be applicable to less experienced operators.
In a multicentre safety study reporting on 156 procedures in 134 patients, percutaneous epicardial access and mapping failed in 10% of cases due to pericardial adhesions after prior surgery or prior pericarditis.41 A total of 14 (9%) acute major complications occurred, eight (5%) related to pericardial access (seven cases of epicardial bleeding and one coronary stenosis).
In addition, three delayed major complications were observed, consisting of a delayed tamponade, one MI due to direct coronary artery injury from ablation and one major pericardial reaction.41 In particular, the latter might preclude a second epicardial approach when adhesions prevent successful access. Other reported complications include intra-abdominal bleeding after diaphragmatic vessel injury, increased defibrillation threshold due to air in the pericardial space and phrenic nerve injury.65–67
Despite the identification of a potential successful ablation site, delivery of RF energy should be withheld in the vicinity of the phrenic nerve (the course of which can be identified by high output pacing) and the coronary arteries (which requires coronary angiography during the procedure). The course of the main branches can be visualised by image integration with pre-acquired multislice CTs (see Figure 4). Finally, RFCA might not be effective due to poor energy transfer in the presence of an epicardial fat layer >4mm, which can cover >26±18.9% of the total epicardial surface.68
Imaging of the Ventricular Tachycardia Substrate
Detailed endo- and epicardial voltage mapping is time consuming and is essentially 2D. The electrically-defined scar may not reflect the complex 3D geometry of the actual scar.
Contrast-enhanced magnetic resonance imaging (CE-MRI) allows the detection of small, intramural and subepicardial scarring in various NICM (see Figure 3). This information may be helpful in planning the ablation procedure and may predict whether an epicardial approach is required.69 In addition, CE-MRI can further characterise infarct scars by differentiating the core infarct and infarct grey-zones, the extent of which has been associated with inducible and spontaneous VT.70,71 Furthermore, animal studies have shown that CE-MRI-defined scar geometry can predict the location of VT re-entry circuits.72,73 Thus, the integration of CE-MRI-derived scar information with electroanatomical mapping may provide important additional information to facilitate VT ablation procedures.
The feasibility and accuracy of integration of CE-MRI-derived scar information with voltage mapping has been demonstrated allowing for visualisation of the 3D scar distribution during ablation procedures (see Figure 5).69,74 Whether CE-MRI-derived scar information can be used to guide substrate-based ablation and translates into improved outcome needs further evaluation.
The reasons for the high VT recurrence rates despite good acute success are not fully understood. The extent of the substrate, disease progression and ongoing remodelling may contribute. In addition, deep intramural circuits targeted from the endocardium or epicardium may be more likely to recur after the healing of ablation lesions. Lesion formation may be improved by the use of realtime contact force measurement.75 In particular, deep septal re-entry circuits may require deeper lesions that might be facilitated by bipolar ablation between two catheters on either side of the septum or by the use of intramural needle ablation.76,77
Major progress has been achieved in the treatment of patients with ventricular arrhythmias by RFCA since its introduction more than 20 years ago. New imaging technologies to improve the identification of the arrhythmogenic substrate are enabling the treatment of fast and unstable VT, thereby reducing subsequent ICD therapies. The integration of different imaging modalities may even further improve outcomes. The most important targets for the next era will be the reduction of recurrences and ‘preventive’ treatment of patients at risk for developing malignant arrhythmias. Ideally preventive ablation may ultimately render ICD treatment obsolete.