Catheter ablation of ventricular tachycardia in nonischemic cardiomyopathy.

The number of patients with nonischemic cardiomyopathy (NICM) undergoing catheter ablation of ventricular tachycardia (VT) has increased by the years, however, there are no randomized studies of VT ablation in this population. Many studies have reported more mixed or inferior outcome after the ablation in patients with NICM as compared to in those with ischemic cardiomyopathy (ICM)-likely because of the heterogeneous VT substrates in each etiology. While, various ablation strategies for substrate modification in the setting of ICM, including low voltage area ablation, late potential abolition, and local abnormal ventricular activity elimination, have been well established, it is still unknown which ablation strategy is effective for prevention of recurrence VTs in NICM patients. Therefore, this review will highlight the recent progress made in VT ablation in patients with NICM.

INTRODUCTION

Ventricular tachycardias (VTs) increase mortality in patients with a structure heart disease.1

To manage the VTs in this population, there are three feasible options: antiarrhythmic drugs (AADs), implantable cardioverter‐defibrillator (ICD), and catheter ablation (CA).

Apart from beta‐blockers, none of the AADs for ventricular arrhythmias has been shown to improve survival; amiodarone, although being the most effective AAD for preventing VT and reducing arrhythmic death,2 doesn't reduce the all‐cause mortality,3 likely because of its long‐term side effects counterbalancing its benefits.4

Implantable cardioverter‐defibrillator is the mainstay of the VTs therapy in those patients who are at risk of sudden cardiac death: however, while the benefit of ICDs in patients with ischemic cardiomyopathies (ICMs) has been well described,4, 5, 6 no randomized trials have yet clarified their beneficial role in nonischemic cardiomyopathies (NICMs).7, 8

Catheter ablation has emerged as an effective option for treating recurrent VTs9, 10 and a recent multicenter study has demonstrated the benefit of a successful ablation in preventing VT recurrences and prolonging the survival.11 In patients with ICMs, a randomized control trail has reported that the rate of a composite outcome (death, VT storm and appropriate ICD shocks) was significantly lower among the patients undergoing catheter ablation than among those receiving an escalated antiarrhythmic drug therapy12; furthermore, in the setting of ICMs, various ablation strategies for substrate modification including low voltage area ablation, late potential (LP) abolition and local abnormal ventricular activity (LAVA) elimination have been well established.13, 14

On the other hand, there are no randomized studies of catheter ablation of VT in NICM patients. Many studies have reported more mixed or inferior outcome after the ablation in patients with NICM as compared to in those with ICM15, 16, 17—likely because of the heterogeneous VT substrates in each etiology and different VT ablation strategies.18

As the number of patients with NICM undergoing VT ablation has increased by the years,19 it is important to review the progress that has been recently made in the ablation treatment of VT in patients with NICMs.

PREPROCEDURAL CONSIDERATION

VT morphology

The preprocedural analysis of the VT morphology is an indispensable tool for planning the ablation and increase the probability of success.20

We reported the correlation between VT morphology and scar area in NICM patients21: in this study, where patients were classified into two groups (anteroseptal or inferolateral scar type) according to the endocardial unipolar voltage, the left inferior VT axis was predictive of an anteroseptal scar (positive predictive value: 100%) and the right superior axis for inferolateral ones (positive predictive value: 89%).

If the clinical VT morphology in a 12‐lead ECG should not be available due to appropriate ICD interventions, we recommend to perform a noninvasive program stimulation (NIPS) or an electrophysiological study (induction of VT) before the ablation, to check the inducibility and VT morphology.

Baseline ECG

On the other hand, the VT is not always inducible before the procedure and its morphology can't be obtained: in these cases, the baseline ECG—its characteristics are well correlated with the unipolar low‐voltage distribution in high‐density endo‐epicardial maps—might be helpful to predict the arrhythmogenic substrate. Oloriz et al22 reported that the conduction disturbance with an atrioventricular block, left bundle branch block and widened QRS was associated with an anteroseptal scar in the endocardium, whereas the low QRS voltage in the limb leads was correlated with voltage abnormalities in the inferolateral area in the epicardium.

Magnetic resonance imaging

Ventricular tachycardia ablation in patients with NICMs is considered to be challenging partly because of the frequent intramural and subepicardial location of the arrhythmogenic substrate, which can often be identified by a magnetic resonance imaging (MRI) scan that may thus have important clinical implications for preprocedural planning and intraprocedural substrate identification.23 Piers et al24 used contrast‐enhanced MRI to describe two typical scar patterns (anteroseptal and inferolateral), accounting for 89% of the arrhythmogenic substrates in patients with NICM. Anteroseptal scars are approached from the endocardium, whereas inferolateral scars frequently require an epicardial approach.

Computed tomography

While MRI is the gold standard for identifying myocardial scars, it is often not feasible in patients with an ICD, for which a safe alternative could be the multidetector computed tomography (CT).

Delayed enhancement cardiac CT can provide a 3D description of the structural substrate at the VT origin, together with a detailed heart anatomy. Preprocedural cardiac CT imaging offers important clues in the planning of VT ablations (Figure 1).25

Figure 1

Late iodine enhancement scan in a patient with postmyocarditis scar. Short‐axis (left→right = base→apex) of late iodine enhancement (LIE) scan acquired according to the method previously validated by Esposito et al25 in a patient with ICD. LIE scan shows a thin subepicardial area of hyperdensity involving the infero‐lateral wall from the base to the apex (A.B.C) and the anterior and lateral apical wall. LIE findings were referable to postmyocarditis scar. Courtesy of Antonio Esposito and Anna Palmisano

Extracorporeal membrane oxygenation

Nakahara et al26 described how, when facing unstable VTs in a NICM setting, the substrate modification approach based on late potential abolition and/or pace‐mapping offered limited success when compared to the ICMs. Therefore, when patients, especially in idiopathic dilated cardiomyopathy (IDCM), have low EF (<30%), and/or episodes of hemodynamically untolerated VTs, it could be reasonable to consider setting up an extracorporeal membrane oxygenation (ECMO) support for VT mapping and ablation, which allows for rhythm stabilization and low procedure mortality.27

WHEN DO WE NEED AN EPICARDIAL ABLATION?

From 2010 to 2016, 523 VT ablations on NICM patients were performed in our center.

Out of them, 263 cases (50%) required an epicardial access, chosen after weighting several factors (Figure 2A).

Figure 2

Proportion of epicardial ablation (A) and late potential presence in each etiology. ABL, ablation; ARVD, arrhythmogenic right ventricular dysplasia; DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy; LP, late potential; VHD, valvular heart disease

Etiology

As it is well known that patients with postmyocarditis or arrhythmogenic right ventricular dysplasia (ARVD) are often characterized by epicardial substrates, the epicardial access could be considered as a first‐line approach. In our experience, 88% of the patients with postmyocarditis and 70% of those with ARVD underwent an epicardial access.

In the setting of IDCM, the need for a first‐line epicardial access has yet to be clarified.

As the previous study on VT mapping showed, scars are often more extended in the epicardium than in the endocardium, and an epicardial ablation is likely to improve the ablation success rate28; however, as we reported recently, it might be reasonable to attempt the epicardial approach only when a free wall location of the scar was be expected.21

MRI

Magnetic resonance imaging is a good tool to guide the decision to a first‐line epicardial approach, because it can easily identify the epicardial extension of the scarred tissue.29 If patients have no implanted device, MRI is recommended before procedure.

ECG

Ventricular tachycardia morphology can be an important clue to identify which patients are likely to benefit from an epicardial approach.30

The previous study importantly suggested that the presence of a q wave in lead I, create a high degree of suspicion for a probable epicardial location in the setting of NICM.31

In patients with ARVD, while the presence of a QS pattern in lead V1‐V3 is predictive of an epicardial RV‐VT, QS pattern in the inferior leads is common in the patients with an epicardial superior axis RV VT.32

The 12‐lead ECG of the baseline rhythm, particularly when there is a contraindication to the MRI or the VT morphology is not available, may also help to exclude the possible epicardial origin of the VT and avoid the epicardial access.22

Electroanatomical findings during ablation

Besides a history of a previously failed endocardial procedure, electroanatomical findings during procedure—such as the absence of LP and low voltage area in the endocardium—provide good reasons to resort to the epicardial access. Additionally, when the unipolar penumbra area, defined as the unipolar scar beyond the bipolar low voltage area, is observed in the endocardium,33 the epicardial mapping can be rewarding.34, 35

Recently, Gökoglan demonstrated the superiority of the end‐epicardial ablation (scar homogenization) over the standard ablation (the epicardial mapping/ablation was performed in patients for whom either the VT was inducible after the endocardial ablation or there was no endocardial scar) in patients with dilated NICMs and VT.15 In the study, after a single procedure and with a mean follow‐up period of 14 ± 2 months, the freedom from any ventricular arrhythmia in the scar homogenization group was 64%, compared with 39% in the standard ablation cohort; consequently, the epicardial ablation might be indicated for this population. On the other hand, a European multicenter study reported that the complication rate related to the epicardial access was not low, even in high experienced centers.36 For the above‐mentioned reasons, the authors suggest that we should carefully evaluate the indication to an epicardial access with a patient‐by‐patient approach.

MAPPING AND ABLATION

The procedures are performed under general anesthesia. Since the stability of the catheter and the quality of the contact depend on the anatomy of the heart and on the site of the ablation, the standard approach in our center involves a double access (retrograde transaortic and antegrade transseptal approach), allowing for a more flexible ablation strategy.

If a first‐line combined epicardial and endocardial mapping approach is undertaken, the epicardial puncture and mapping are performed before transseptal puncture.

What follows is a summary of our VT ablation workflow:

Activation mapping and substrate ablation:

Patients presenting incessant VTs at the beginning of the procedure undergo an activation mapping‐guided CA and, after the VT termination, a substrate modification is attempted during sinus or paced rhythm.

Patients in sinus rhythm (SR) undergo a substrate mapping, followed by a programmed ventricular stimulation and ablation guided by the activation map built during the VT; after the VT termination, the CA continues during SR, aiming at completing the substrate modification.

Activation mapping ablation: in cases of inducible VTs and absence of targetable substrate during SR.

Substrate ablation: in patients in whom the VT was not inducible, the CA was performed during SR aiming for the achieving the substrate modification.

Substrate modification was performed with the aim of abolishing the LPs or, in case of absence of the LPs, targeting the LAVAs or the bipolar/unipolar low voltage area (<1.5 and <8.3 mV, respectively). For mapping, we recommend using multielectrode catheters, such as the Pentaray (Biosense Webster, Diamond Bar, CA), the Livewire (St. Jude Medical, Saint Paul, MN) and the Orion (Boston Scientific, Marlborough, MA) mapping catheter: acquiring the points is rapid and the high‐resolution permits to differentiate near‐field from far‐field ventricular signals, not as easy with conventional mapping catheters; furthermore, using a multielectrode catheter facilitates the identification of the conduction system site, leading to a clear bundle branch reentry diagnosis during the procedure.

The procedure end‐point is always the combination of LP abolition and VT noninducibility, verified by performing a programmed ventricular stimulation (≤4 extrastimuli) at the right ventricular apex and at multiple left ventricular sites.

CONSIDERATIONS BY EACH ETIOLOGY

We believe it is important to consider practical ablation strategies according to each etiology.

IDCM

Idiopathic dilated cardiomyopathy is the most common etiology among NICM patients, accounting for about 50% of our whole population undergoing a VT ablation (Figures 3 and 4).

Figure 3

Distribution of etiologies in NICM patients. ARVD, arrhythmogenic right ventricular dysplasia; IDCM, idiopathic dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy; NICM, nonischemic cardiomyopathy; VHD, valvular heart disease

Figure 4

Voltage map in a patient with IDCM. Voltage map in bipolar (left panel) and unipolar (right panel) shows low voltage area (LVA) at basal and septal area in right anterior oblique view (RAO). Ablation (pink tags) targeting diastolic pathway of ventricular tachycardia (VT) at the anterobasal area was performed, leading to VT termination. IDCM, idiopathic dilated cardiomyopathy

However, when compared to ICM patients, several studies have suggested unsatisfying long‐term outcomes after the ablation,16, 17, 28, 37, 38 probably because of the less defined arrhythmia substrate (patchy or diffuse microscarring process) and the frequent intramural or subepicardial location.

Hsia et al39 studied 19 patients with IDCM and VT using electroanatomic mappings, observing how the regions of abnormal electrograms were mainly located at the basal and lateral aspects of the LV, adjacent to the mitral valve annulus.

Soejima et al28 described the importance of the epicardial mapping and ablation and reported on the scar being predominantly in the basal perivalvular area; the concept of a basal interventricular septum scar was subsequently further investigated by Haqqani et al.40 These findings suggest the possibility of an intramural or epicardial substrate, which may translate into limited results after ablation.

On the other hand, Muser et al41 recently reported favorable outcomes on a population of 282 patients with IDCM, with a VT‐free survival after the ablation of about 70% at a 5 year follow‐up. Notably, according to his experience, the majority of the procedures can be effectively approached through an endocardial strategy only, whereas just 32% of the patients required an epicardial ablation; this further confirms the necessity of an ad‐hoc evaluation of every case, as no clear criteria is yet available to identify the need of an epicardial approach.

Finally, a substrate modification strategy targeting the LPs appears to be less applicable in patients with ICMs, because of the LPs being less frequently observed in this population in our study, only 44% of the IDCM patients showed LPs at baseline (Figure 2B).

ARVD

In ARVDs, the arrhythmogenic substrate often involves the perivalvular area (the tricuspid annulus and pulmonic valve annulus), mainly at the right ventricular free wall, while the apex are typically spared42; in this setting, epicardial ablations are more frequently required compared with patients with ICMs.43

In ARVD patients undergoing catheter ablation, the freedom from VT recurrence is generally good during long‐term follow‐up.44 (Figure 5)

Figure 5

Late potential (LP) mapping and VT activation pattern in a patient with ARVD. Representative case of LP mapping and ablation. 3D activation map in patients with arrhythmogenic right ventricular dysplasia. During creating the sinus activation map (left panel), LPs was recorded after QRS offset (blue arrow), while, during the ventricular tachycardia (VT) (right panel), these same LPs became the whole diastolic potential (orange arrow) connecting the first QRS to the next one. Therefore, we performed the ABL aiming at the area where we had recorded the LPs, finally obtaining the VT noninducibilty

Kirubakaran et al32 reported 29 ARVD patients undergoing VT ablation, classifying their cardiomyopathies as “electrical” or “structural” according on the presence of major structural criteria. In patients with an electrical cardiomyopathy the scar was only found close to the epicardial surface, mainly in the outflow tract, whereas patients with a structural disease showed a greater involvement of the endocardium. Targeting the LPs proved to be effective to prevent VT recurrences in both groups, although, when compared with the electrical cardiomyopathies, patients with a structural RV cardiomyopathy showed a trend toward higher recurrence rates (40% vs 15%).

Postmyocarditis

Postmyocarditis seems to be characterized by an arrhythmogenic substrate set predominantly in the epicardium.45 The previous study reported how 23 patients with postmyocarditis (88% of the study population) required an epicardial ablation, and that catheter ablation was a safe and effective solution in the short term (77% of the patients remained free of VT recurrences during the 2 year follow‐up period).46

Due to the lateral LV wall localization of the arrhythmogenic substrate, the epicardial ablations were frequently limited by the presence of the coronary arteries and phrenic nerve; 19% of the patients required their phrenic nerve to be displaced with a valvuloplasty balloon, allowing to complete the LP abolition in the majority of the cases (Figure 6). However, the proximity of a coronary artery to the ablation site remains an unresolved issue.

Figure 6

Phrenic nerve displacement with balloon in a patient with myocarditis. Fluoroscopic images of the displacement of the phrenic nerve using a large balloon (20 mm × 45 mm) in the right anterior oblique view in the myocarditis case. When the balloon was inflated, the phrenic capture successfully disappeared. After confirming the PN displacement, a late potential abolition was performed at that site. ABL, ablation catheter

Valve heart disease

Sustained VTs can occur any time after undergoing after a valve surgery. Eckart et al47 reported that periannular scars were frequently observed in patients with VT developed after the valve repair.

Although the main challenge when dealing with this population is the limited LV accessibility, hindered by the mechanical prosthetic valve, Soejima et al48 described the feasibility of the epicardial ablation in patients who had previously undergone an aortic and mitral valve mechanical repair; all patients presented abnormally low voltage areas with fractionated or delayed isolated potentials on the apical epicardium, and a microscopic pathological evaluation of the resected tissue of two patients revealed more dense fibrosis on the epicardium than the endocardium. These findings may allow the option of an ablation strategy based on the epicardial access only to be considered even in case of previous mechanical prosthetic valve surgery.

Hypertrophic cardiomyopathy

In patients with hypertrophic cardiomyopathies (HCMs), the occurrence of monomorphic VTs is rare. Dukkipati et al49 studied 10 such patients, identifying an epicardial scar in 8 of them (80%) and an endocardial scar in 6 (60%); 78% of the patients remained free from VT recurrences during the follow‐up period (median of about 3 years).

Lamin A/C cardiomyopathy

About 10% of the DCM patients present pathogenic genetic mutations in proteins encoded by the Lamin A/C (LMNA) gene. This autosomal dominant heart disease is generally more severe than other kind of DCMs, and it's characterized by a progressive conduction system impairment and a high risk of life‐threatening ventricular arrhythmias.50 The arrhythmogenic substrate in patients with the LMNA mutation is usually represented by an intramural and/or basal perivalvular scar, which probably explains why performing a catheter ablation in this setting is particularly challenging and less effective.51

Cardiac sarcoidosis

Cardiac sarcoidosis is usually characterized by a severe progressive heart failure, conduction system disorders and malignant ventricular arrhythmias; unfortunately, CA in these patients is burdened by a high recurrence rate, coherent with the rapid progression of the pathology.52 A recent study on this condition identified the VT mechanisms as being either scar‐ or Purkinje‐related, and showed how a systematic approach combining amiodarone, a systemic corticosteroids therapy and CA could effectively reduce the incidence of VT recurrences.53

WHAT SHOULD WE DO?

Recently, a multicenter study reported positive data on VT ablation in a huge number of patients with NICMs: among the 133 529 patients hospitalized with a principal diagnosis of VT in NICMs, 14 651 (11.0%) underwent an ablation.19The in‐hospital mortality numbered 172 of 14 318 (1.2%) patients in the catheter ablation group that, when compared with the 297 deceased among the 14 156 (2.1%) patients undergoing a medical therapy, led the authors to conclude that catheter ablation was the safest option.

Although randomized trials will be necessary to confirm these findings, such a large‐scale study surely encourage us to consider the ablation of VT more feasible option in the setting of NICMs.

Our group previously reported that a combined endpoint of LP abolition and VT noninducibility was effective to increase the long‐term arrhythmia‐free survival in patients with ICM13; on the other hand, it is still unknown whether such benefit extends also to patients with NICM.

In our experience, comprising 403 patients with NICMs, the above mentioned combined endpoint was independently associated with free survival from VT (hazard ratio (HR) 0.42, 95% Confidence Interval (CI) [0.28‐0.64], P < 0.0001) and cardiac death (HR 0.42, 95%CI [0.21‐0.82], P = 0.001); more specifically, the 1‐year VT free survival rate differed across the aetiologies, with a 62% for patients with DCMs, 79% in case of myocarditis, 86% for ARVDs, 68% in presence of a valvular heart disease and 72% in the remaining etiologies. We concluded that, even for patients with NICMs, the strategy of LP abolition and noninducibility could bear positive results in the long term. However, we again strongly recommend to plan the ablation according to the particular characteristics of every single patient, as the blind application of general criteria might prove misleading.

NEW TOOLS FOR VT ABLATION

A new multipolar grid mapping catheter54 has recently been made available and, being able to create different voltage/activation maps considering the bipolar electrograms from orthogonal wavefront direction relative to the electrodes orientation, it might be useful for mapping the ventricle.

We have been investigating the impact of a bipolar ablation to treat VTs with a septal substrate, approached with two ablation catheters opposing each other across the septum to create a transmural lesion (Figure 7).55 For intramural lesion, irrigated needle ablations might be of future help.56

Figure 7

Bipolar ablation in a patient with IDCM. Right ventricle (RV) and left ventricle (LV) in left anterior oblique view (LAO). Orange arrow indicates the correlation between the two ablation catheter's tips during RF delivery to create transmural lesion at septum. IDCM, idiopathic dilated cardiomyopathy

CONCLUSION

As the number of VT ablations in patients with NICMs is rising, it is more than ever necessary to identify the best strategy to treat this population. To attain this goal, however, further studies are necessary.

CONFLICT OF INTEREST

Authors declare no conflict of interests for this article.