- Email: [email protected]
Infarct transmurality as a criterion for first-line endo-epicardial substrate–guided ventricular tachycardia ablation in ischemic cardiomyopathy
Author's Accepted Manuscript
Infarct Transmurality as a Criterion for First-Line Endo-Epicardial Substrate-Guided Ventricular Tachycardia Ablation in Ischemic Cardiomyopathy Juan Acosta MD, Juan Fernández-Armenta MD, Diego Penela MD, David Andreu MSc, PhD, Roger Borras MSc, Francesca Vassanelli MD, Viatcheslav Korshunov MD, Rosario J Perea MD, PhD, Teresa M de Caralt MD, PhD, Jose T Ortiz MD, PhD, Guillermina Fita MD, PhD, Marta Sitges MD, PhD, Josep Brugada MD, PhD, Lluis Mont MD, PhD, Antonio Berruezo MD, PhD
PII: DOI: Reference:
S1547-5271(15)00892-9 http://dx.doi.org/10.1016/j.hrthm.2015.07.010 HRTHM6353
To appear in:
Heart Rhythm
www.elsevier.com/locate/buildenv
Cite this article as: Juan Acosta MD, Juan Fernández-Armenta MD, Diego Penela MD, David Andreu MSc, PhD, Roger Borras MSc, Francesca Vassanelli MD, Viatcheslav Korshunov MD, Rosario J Perea MD, PhD, Teresa M de Caralt MD, PhD, Jose T Ortiz MD, PhD, Guillermina Fita MD, PhD, Marta Sitges MD, PhD, Josep Brugada MD, PhD, Lluis Mont MD, PhD, Antonio Berruezo MD, PhD, Infarct Transmurality as a Criterion for First-Line Endo-Epicardial Substrate-Guided Ventricular Tachycardia Ablation in Ischemic Cardiomyopathy, Heart Rhythm, http://dx.doi.org/10.1016/j. hrthm.2015.07.010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Infarct Transmurality as a Criterion for First-Line EndoEpicardial Substrate-Guided Ventricular Tachycardia Ablation in Ischemic Cardiomyopathy Short Title: Infarct Transmurality and Endo-Epi VT Ablation
Juan Acosta, MD1; Juan Fernández-Armenta MD1, Diego Penela, MD1; David Andreu, MSc, PhD1; Roger Borras, MSc1; Francesca Vassanelli, MD1; Viatcheslav Korshunov, MD1; Rosario J Perea, MD, PhD2; Teresa M de Caralt, MD, PhD2, Jose T Ortiz, MD, PhD1, Guillermina Fita, MD, PhD1; Marta Sitges, MD, PhD1, Josep Brugada, MD, PhD1; Lluis Mont, MD, PhD1; Antonio Berruezo, MD, PhD1
1
Arrhythmia Section, Cardiology Department, Thorax Institute, Hospital Clínic and IDIBAPS (Institut d’Investigació Agustí Pi i Sunyer), Barcelona, Catalonia, Spain 2
Radiology Department, Hospital Clinic, University of Barcelona, Barcelona, Catalonia, Spain
Conflict of Interest: All authors have no conflict of interest to declare.
Address for Correspondence: Antonio Berruezo, MD, PhD Arrhythmia Section, Cardiology Department. Thorax Institute, Hospital Clinic C/ Villarroel 170 08036 Barcelona Phone: 0034 93 2275551 Fax: 0034 93 4513045
1
Email: [email protected]
Abstract Background: There is no consensus on the appropriate indications for epicardial approach in substrate ablation of post-myocardial infarction (MI) ventricular tachycardia (VT). Objective: Infarct transmurality (IT) could identify patients that would benefit from a combined first-line endo-epicardial approach. Methods: Before ablation, IT was assessed by contrast-enhanced magnetic resonance imaging (hyperenhancement ≥75% of wall thickness in ≥1 segment), echocardiography (dyskinesia/akinesia + hyperrefringency + wall-thinning), computer tomography (wall thinning), or scintigraphy (transmural necrosis). Prospectively from January 2011, endocardial approach was used in patients with subendocardial MI (group 1) and combined endo-epicardial approach in patients with transmural MI (group 2). Outcomes in both groups were compared with patients with transmural MI and only endocardial approach due to prior cardiac surgery or procedure performed before January 2011 (group 3). Primary endpoint was VT/VF recurrence-free survival. Results: Ninety patients (92.2% men, 67.4±9.8 years) undergoing VT substrate ablation were included: group 1, N=34; group 2, N=24; group 3, N=32. During a mean followup of 22.5±13.7 months, 5 patients in group 1 (14.7%), 3 patients in group 2 (12.5%) and 13 patients in group 3 (40.6%) had VT recurrences; p=0.011. Time to recurrence was shortest in group 3 (log-Rank p=0.018). Endocardial approach in patients with transmural MI was associated with an increased risk of recurrence (hazard ratio 4.01; 95%CI 1.41-11.3; p=0.009). Conclusion: Endocardial approach in patients with transmural MI undergoing VT substrate ablation is associated with an increased risk of recurrence. IT may be a useful criterion in the decision to choose a first-line combined endo-epicardial approach.
Key Words: Infarct Transmurality. Epicardial Approach. Ventricular Tachycardia Ablation.
2
Abbreviation List CC: conducting channel. ce-CMR: contrast-enhanced cardiac magnetic resonance. Ce-MDCT: contrast-enhanced multidetector computed tomography. EAM: electroanatomic map. E-DC: electrogram with delayed component. IT: infarct transmurality. LV: left ventricle. MI: myocardial infarction. RF: radiofrequency. VF: ventricular fibrillation. VT: ventricular tachycardia.
Introduction Substrate-based catheter ablation is an effective therapeutic option in patients with recurrent episodes of scar-related ventricular tachycardia (VT)
1, 2
. However, data
obtained from large series of patients reveal that prevention of VT recurrence is not achieved after conventional endocardial ablation in a significant proportion of patients 3, 4
. In the case of ischemic cardiomyopathy, VT recurrences after endocardial substrate
ablation might be due to the persistence of epicardial circuits in some cases. A recent study has shown that 63% of patients with post-myocardial infarction (MI) transmural scar exhibit epicardial border zone channels 5. Therefore, epicardial substrate could play an important role in this subgroup of ischemic patients. Since its description by Sosa et al 6, epicardial ablation of VT has been shown to be beneficial in several clinical scenarios such as Chagas disease 7, right ventricular dysplasia
8
, and nonischemic cardiomyopathy
9
. However, due to its technical
complexity and potential risks, it is usually restricted to patients with previous failed endocardial ablation attempts 10.
3
A recent study has shown that complete VT substrate elimination is related to better clinical outcomes after ablation
11
. Therefore, ablation strategies that pursue complete
substrate accessibility may better achieve complete VT substrate elimination and improve current results of post-MI VT ablation. In addition, there is no consensus on the appropriate timing of epicardial approach in post-MI VT substrate ablation procedures. Studies by Di Biase et al and Tung et al have proposed that the endoepicardial approach in post-MI VT ablation, either as a first-line strategy or after failed endocardial ablation, is associated with improved clinical outcomes
12, 13
. However, in
these studies a significant proportion (27% and 67%, respectively) of patients who underwent epicardial mapping did not exhibit epicardial arrhythmogenic substrate. Therefore, criteria that better identify patients requiring epicardial mapping and ablation are needed. We hypothesized that complete substrate accessibility predicts long-term outcomes of post-MI VT substrate ablation and that infarct transmurality (IT) could support the appropriate selection of patients that will benefit from an endo-epicardial approach.
Methods Study Population Consecutive post-MI patients (N=90) referred for catheter ablation of documented infarct-related sustained monomorphic VT from November 2009 to February 2015 were included. The study complies with de Declaration of Helsinki. The local Ethics Committee approved the study protocol, and all included participants signed the informed consent.
4
Infarct Transmurality Assessment Prior to the ablation procedure, IT was assessed in all patients by at least one of the following methods: contrast-enhanced cardiac magnetic resonance (ce-CMR), echocardiography, iodine-enhanced multidetector computed tomography (MDCT) or cardiac single photon emission computed tomography (SPECT). According to the imaging technique performed, IT was assessed as follows: a) Patients with prior ce-CMR. In all patients without claustrophobia or classical contraindications for magnetic resonance (n=41; 45.6%), a preprocedural ce-CMR study was performed in a 3T scanner (Magnetom Trio-Tim, Siemens, Erlangen, Germany). Contrast-enhanced images were acquired 7 minutes after bolus injection of 0.2 mmol/kg Gadobutrol (Gadoyist, Bayer Hispania, Barcelona, Spain) using a commercially available, freebreathing,
ECG-gated,
navigator-gated,
3D
inversion-recovery,
gradient-echo
technique. The ce-CMR images were analyzed by experienced cardiologists and radiologists to depict the presence of scarred tissue for each left ventricle (LV) according to the 17-segment model 14. According to previous descriptions, the presence of hyperenhancement involving ≥75% of wall thickness was defined as transmural MI 15
.
b) Patients without prior ce-CMR In patients who could not undergo ce-CMR due to classical contraindications (N=49; 54.4%), definition of IT required the presence of transmurality criteria in at least 1 of the following imaging techniques: Echocardiography A preprocedural comprehensive transthoracic echocardiography was performed. Twodimensional echocardiographic images were obtained from the standard parasternal,
5
apical, and subcostal views. According to previous publications
16-18
, scar segments
were assumed to have lost most of their muscle fibers and be mainly composed of connective tissue if they showed all of the following echocardiographic patterns: 1) a reduction in end-diastolic wall thickness ≤ 0.5 cm; 2) hyperrefringency; and 3) akinesia or dyskinesia. This echocardiographic pattern was judged as being consistent with transmural scar segments (Figure 1, panels A-C). Echocardiograms were performed by experienced operators and were reviewed by two experienced observers in order to define the presence of infarct transmurality criteria. Contrast-enhanced MDCT (ce-MDCT) Preprocedural ECG-gated ce-MDCT was performed on a 128-slice CT scanner (Somatom Definition Flash, Siemens Healthcare, Erlangen, Germany). Images were acquired during an inspiratory breath-hold with tube current modulation set on enddiastole. CT angiographic images were acquired during the injection of a 180 mL bolus of Iopromide 370 mg I/mL (Ultravist, Bayer Hispania, Barcelona, Spain) at a rate of 5 mL/s. As has been reported 19-21, wall thinning at ce-MDCT correlates with low voltages areas in electroanatomic maps (EAM). According to this, and based on reference values of LV wall thickness
22
, two criteria were used to define IT by ce-MDCT: 1) wall
thickness ≤5 mm; and 2) presence of aneurysm (Figure 2, panels A-C). SPECT performed within 6 months before procedure A standard stress SPECT was performed using a 1-day protocol with 2-metoxil-isobutilisonitrila-99mTC. In a semicircular orbit from the right anterior oblique to the left posterior oblique projections, 64 views were obtained using a dual-head gammacamera. Tomograms were displayed as short-axis and horizontal and vertical long-axis slices, and as quantitative polar maps. These images were analyzed to depict nonviable myocardial segments. The presence of an irreversible perfusion defect with an extension
6
>75% of myocardial wall thickness was considered to be consistent with a transmural MI.
Electrophysiology Study and Substrate Mapping The electrophysiology study was performed under conscious sedation. An endocardial high-density, 3D, electroanatomic, bipolar voltage map of the LV was obtained during stable sinus rhythm using the CARTO system (Biosense, Inc, Diamond Bar, CA). Standard voltage thresholds (<0.5 mV for the core and <1.5 mV for the border zone) were used to define the scar on the EAM. The conducting channels (CCs) on the EAM were identified as either voltage channels, corridors of border zone within scar core areas or between a core area and the mitral annulus (identification was facilitated by voltage scanning of the upper and lower voltage thresholds) 23 or late potential channels, defined as ≥2 consecutive electrograms with delayed components (E-DCs) localized in the scar area, connecting with healthy tissue, impossible to visualize with a voltage threshold modification, and showing an activation sequence of the delayed component 8, 24
. In order to facilitate mapping, CCs were not always tracked all along their trajectory.
Instead, E-DCs were tagged and dichotomously classified as entrance or inner CC points, depending on delayed-component precocity during sinus rhythm. The CC entrance was defined as the E-DC with the shortest delay between the far-field component of healthy/border zone muscle (low frequency, usually high voltage) and the local component (delayed, high frequency, usually fractionated and low voltage) corresponding to the local activation of myocardial fibers in the scar. To avoid targeting healthy tissue beyond the scar area, CC entrances were tagged in a zone with 0.5-1.5 mV voltage 8, 24.
7
Epicardial Approach Beginning in January 2011, a first-line endo-epicardial approach was performed in all patients with transmural MI and no previous cardiac surgery. Percutaneous pericardial puncture was performed as described by Sosa et al using the subxiphoid approach 6. Epicardial mapping was performed similar to the endocardial mapping described above.
VT Ablation All patients underwent substrate-guided ablation using the “scar dechanneling” technique
8, 24
. Thus, radiofrequency (RF) energy was delivered at the previously
identified CC entrances as previously described
24, 25
. A change in the CC activation
sequence of the delayed components, or their disappearance during RF application, indicated a CC entrance block. These changes were detected by continuously recording local activation in the CC with the proximal dipoles of the ablation catheter or by a remap of the scar area. RF ablation was performed with a Navistar catheter (Biosense Webster) and was controlled by a temperature limit of 45ºC with a power limit of 50W at the endocardium and 40-50W at the epicardium. The catheter irrigation rate during RF application was 26 mL/min in the endocardium and 17 mL/min in the epicardium. Coronary arteries were localized through the integration of CT/CMR into the navigation system. Phrenic nerve course was obtained by high-output epicardial pacing. A postablation remap was always performed to document the elimination of all the CCelectrograms and to eliminate the remaining E-DCs by back-up RF applications. Clinical and nonclinical induced VTs after scar dechanneling were targeted for ablation. VT isthmus and exit sites were defined by entrainment mapping if the VT was tolerated and by pace mapping if not tolerated.
8
Patient Groups According to the type of approach (endocardial vs endo-epicardial) and IT (transmural vs no transmural MI), patients were classified by substrate accessibility to permit complete substrate ablation: Group 1, nontransmural MI and only endocardial approach; Group 2, transmural MI and endo-epicardial approach; Group 3 (incomplete substrate accessibility), transmural MI and only endocardial approach, due to prior cardiac surgery and procedure performed before January 2011.
Procedural Success and Follow Up Acute success was defined as noninducibility of any monomorphic VT at the end of the procedure. Partial success was considered when the clinical VT was successfully ablated but other monomorphic VTs remained inducible. Office visits for clinical evaluation and ICD interrogation were scheduled every 6 months. The primary endpoint was the occurrence of VT or ventricular fibrillation (VF). Any sustained VT, whether or not ICD intervention was required, and any VF episode were considered a recurrence during follow-up. The secondary endpoint was all-cause mortality.
Statistical Analysis Continuous variables are presented as mean ± standard deviation. To compare means of two variables the Student’s t test, Mann-Whitney U test or Anova test were used as appropriate. Categorical variables were expressed as total number (percentages) and compared between groups using Chi-square test. Kaplan-Meier survival analysis was used to analyze the time to VT recurrence and redo, and log-rank test was used to detect significant differences among groups. The baseline clinical characteristics, recurrence and mortality were analyzed by including each patient only once in either group (per
9
patient analysis) The effect of different variables on (event-free) survival was investigated using the Cox proportional hazards model. Variables that showed a statistically significant effect on (event-free) survival in univariate analyses were entered in a multivariate Cox proportional hazards model using a backward stepwise selection to obtain the final model. At each step, the least significant variable was discarded from the model, until all variables in the model reached a P-value below 0.10. The number of variables that could enter the multivariate was limited using the P,m/10 rule to prevent over-fitting the model. For all tests, a p value <0.05 was considered significant. Statistical analysis was performed using R software for Windows version 3.1.2 (R project for statistical computing; Vienna, Austria) and SPSS version 18.0 (SPSS, Inc, Chicago, IL)..
Results A total of 90 patients (92.2% men, 67.4±9.8 years) undergoing VT substrate ablation were included (Figure 3).
Infarct Transmurality and Patient Groups. A total of 41 patients (45.6%) underwent ce-CMR before ablation. Thirty-two of them (78%) exhibited transmural MI. In the remaining 49 patients, IT was assessed by echocardiography, ce-MDCT, or SPECT (Supplemental Table 1). Among them, 24 (49%) met transmurality criteria in at least one of the imaging techniques performed. As a result, non-transmural MI was found in 34 patients (37.8%) who underwent only an endocardial approach (group 1). The remaining 56 patients exhibited transmural MI before the procedure; 24 (26.7%) underwent the endo-epicardial approach (group 2) and 32 (35.6%) the endocardial approach (group 3). It should be noted that in the majority of patients in whom ce-CMR could not be performed, infarct transmurality assessment was based on two imaging techniques (CT+echo or echo+ SPECT). No cases of discordance between imaging techniques were observed using the criteria described
10
(Supplemental Table 1).
Baseline clinical characteristics are summarized in Table 1. No differences were found between groups.
Substrate Mapping In groups 1 and 3, patients underwent only endocardial mapping; in group 2, a combined endo-epicardial approach during sinus rhythm was performed. Epicardial access was attempted in 24 (26.6%) patients and achieved in 23 (95.8%). The epicardial approach was not successful during the first procedure in only 2 patients; a successful procedure with epicardial approach was performed 4 days later in one patient, and in the other a redo with surgical epicardial approach was performed due to recurrence. Data from these substrate maps are summarized in Table 2. A total of 34 procedures with endocardial approach were performed in group 1 patients, 26 procedures with endoepicardial approach in group 2 patients, and 32 procedures with endocardial approach in group 3 patients. No statistically significant differences in endocardial scar area were found between groups. However, transmural MIs (groups 2 and 3) presented a slightly higher number of E-DCs than subendocardial MIs, albeit nonsignificant (Table 2). All patients with IT criteria that underwent epicardial mapping (N=24) had low voltage areas in the epicardium, and 21 of them (87.5%) had arrhythmogenic substrate, expressed as E-DCs. The proportion of patients meeting transmurality criteria was significantly higher in the group assessed by ce-CMR (78%) vs IT assessment by echocardiography, ce-MDCT or SPECT (49%); p=0.004. Although no statistically significant differences in endocardial and epicardial scar areas were observed between these two patient groups, a tendency towards higher values of endocardial and epicardial scar areas and numbers of E-DC
11
was observed in patients with IT according to echocardiogram/ce-MDCT/SPECT assessment (Supplemental Table 2). This suggests that the transmurality criteria proposed for ce-CMR may be less rigorous than those defined for the other three imaging techniques.
VT ablation. Acute Results All patients underwent substrate ablation with the scar dechanneling technique: endocardial in groups 1 and 3 and endo-epicardial in group 2. Complete scar dechanneling could be achieved in 32 patients (94.1%) in group 1, 20 patients (83.3%) in group 2 and 25 patients (78.1%) in group 3; p=0.170. After substrate ablation, 73 inducible residual VTs were induced in 40 patients (44.4%). The rate of residual VT inducibility was similar in all three patient groups: 13 patients (38.2%) in group 1, 8 patients (33.3%) in group 2, and 15 patients (46.9%) in group 3; p=0.572. Sixty-six (90.4%) of these residual VTs were targeted for ablation, 42 guided by activation mapping and 24 by pacemapping. In procedures with an endo-epicardial approach, a total of 9 residual VTs were induced and 2 (22.2%) of them had an epicardial origin. After residual VT ablation, the noninducibility rate of monomorphic sustained VT increased from 55.5% to 80%. No differences in noninducibility rate were observed between groups: 29 patients (85.2%) in group 1, 22 patients (91.6%) in group 2, and 24 patients (75%) in group 3; p=0.235.
Procedure-Related Complications Nine patients (10%) presented complications related to the procedure: 3 in group 1 (8.8%), 5 in group 2 (20.8%), and 1 in group 3 (3.1%); p=0.08. Complications in group 1 consisted of 1 complete AV block, 1 femoral hematoma and 1 cardiac tamponade
12
after endocardial ablation requiring pericardiocentesis. Complications in group 2 consisted of 1 cardiac tamponade requiring pericardiocentesis, 1 complete AV block requiring CRT-ICD implantation, 1 case of phrenic nerve palsy, 1 hemothorax and 1 transient ischemic attack without sequela. It should be noted that in patients with an endo-epicardial approach, only 3 complications were potentially related to the epicardial approach. The only complication in group 3 was 1 transient ischemic attack without sequelae.
Follow-up Mean duration (±SD) of follow-up was of 22.5±13.7 months. During follow-up, antiarrhythmic treatment was maintained in 22 patients (24.4%): 11 patients in group 1 (32.3%), 2 in group 2 (8.3%) and 9 in group 3 (28.1%); p=0.083. Recurrences of sustained VT were observed in 21 (23.3%) patients. Of these, 7(33.3%) received ICD shock and 8 (38%) had VT episodes that were terminated by antitachycardia pacing. Five (23.8%) patients with VT episodes were monitored in the VT detection zone and did not receive any therapy. One (4.7%) patient without ICD due to comorbidities and low life expectancy experienced a VT recurrence that required an external shock. No recurrences of VF episodes were observed. Patients with incomplete substrate accessibility (group 3) showed a significantly higher event rate for the endpoint of VT recurrence: 40.6% vs 14.7% in group 1 and 12.5% in group 2; p=0.011. Additionally, Kaplan-Meier analysis showed a significantly lower VT/VF recurrence-free survival in group 3 patients (log-Rank p=0.018) (Figure 4). Table 3 shows univariate and multivariate Cox regression analysis results for the study endpoint. Univariate analysis identified an association between 2 variables and the primary endpoint: end-procedure VT/VF inducibility (HR 2.81 [1.18-6.66], p=0.019)
13
and endocardial approach in transmural MI (HR 3.89 [1.38-11], p=0.01). No association was found between antiarrhythmic treatment during follow-up and the primary endpoint [HR 0.43 (0.18-1.02), p=0.056]. The multivariate analysis revealed that both endprocedure VT/VF inducibility (HR 3.05 [1.27-7.35], p=0.013) and endocardial approach in transmural MI were independent predictors of a sustained ventricular arrhythmia episode (HR 4.03 [1.42-11.43], p=0.009). Four (4.4%) patients died during follow-up: 3 (75%) due to advanced heart failure and 1 (25%) due to noncardiac cause. No differences in mortality were observed between groups: 1 patient died in group 1 (2.9%), 1 in group 2 (4%), and 2 in group 3 (6.2%); p=0.789.
Redo procedures A redo procedure was performed in 7 (33.3%) of the 21 patients who reached the study endpoint. All of them had a transmural MI and had undergone a previous endocardial ablation (group 3), due to prior cardiac surgery in 1 case, failure of previous epicardial approach in 1 case (which required a surgical epicardial approach), and an ablation performed before January 2011 in 5 cases. Therefore, a redo with epicardial approach was performed in 6 cases, while in the patient with previous cardiac surgery a new procedure with only endocardial approach was performed. Findings of the redo procedures are summarized in Supplemental Table 3. Briefly, all patients with transmural MI who underwent epicardial mapping consistently showed an arrhythmogenic epicardial substrate.
14
Discussion The present study describes the feasibility and benefits that could be expected with this novel image-based decision strategy for choosing the approach (endocardial vs endoepicardial) that will lower the recurrence rate in post-MI VT substrate ablation procedures. The decision is based on the identification of IT with imaging techniques routinely used in clinical practice. The study showed that patients with transmural MI who undergo only endocardial ablation are at increased risk of VT recurrence. To date, there is no consensus about the appropriate timing of an epicardial approach in post-MI VT substrate ablation procedures. It has been proposed that the persistence of epicardial substrate might be an important cause of VT recurrence in patients who had undergone a previous endocardial ablation 10. This has led to suggestions of performing an epicardial approach in patients with prior failed attempts of endocardial ablation 27
. In studies by Tung et al
13
and Di Biase et al
26,
12
, the endo-epicardial approach has
been shown to improve outcomes in patients with post-MI VT after substrate ablation; however, epicardial ablation was not performed in a significant proportion of patients due to the absence of epicardial substrate. In the study by Di Biase et al, in which epicardial approach was performed systematically, epicardial substrate was found in only 33% of patients
12
, whereas Tung et al reported absence of epicardial targets in
26.4% of cases, in which an epicardial approach was performed due to previous failed endocardial ablation, intracardiac thrombus, or electrocardiographic criteria
13
. Thus,
according to these data, better criteria are needed to identify those patients with post-MI VT that could benefit from epicardial mapping and ablation. It has been recently shown that the presence and distribution of scar provides useful clinical information to localize the target ablation substrate of VT. Andreu et al reported that the presence of epicardial hyperenhancement in any segment identified an
15
epicardial origin of the clinical VT with a high sensitivity and specificity
28
.
Additionally, it has been shown that a significant proportion of patients with transmural MI exhibit epicardial border zone channels 5. In the present study, epicardial approach was performed only if a transmural MI was observed in preprocedural cardiac imaging techniques. As a result, 87.5% of the patients that underwent epicardial mapping had an arrhythmogenic substrate, suggesting that the presence of a transmural MI correctly identifies those patients with potentially arrhythmogenic epicardial substrate. It should be noted that a tendency towards less epicardial substrate was observed in patients with IT according to ce-CMR, suggesting that it might be appropriate to define more rigorous transmurality criteria for ce-CMR for the specific purpose of deciding to perform an epicardial approach in post-MI patients undergoing VT substrate ablation. The major finding of the present study is that patients with transmural MI undergoing only endocardial ablation are at increased risk of VT recurrence. At the same time, no differences in the incidence of VT recurrence were found between patients with transmural
MI
who
underwent
endo-epicardial
ablation
and
patients
with
subendocardial MI in whom only an endocardial approach was performed. These results are consistent with the study by Jais et al, in which complete elimination of substrate was associated with a superior clinical outcome
11
. Thereby, substrate guided ablation
techniques, such as scar dechanneling, pursue complete substrate elimination under the assumption that substrate that is no related with clinical or inducible VTs at the moment of the procedure can activate and become a VT isthmus during follow-up. Therefore, the higher incidence of VT recurrence observed in patients with transmural MI and only endocardial approach could be due to the persistence of epicardial substrate. Given the differences observed in the requirement of CABG between groups 2 and 3, it could be argued that prior cardiac surgery could be associated with a higher incidence of VT
16
recurrence. However, to our best knowledge, there is no data about the potential role of prior CABG/cardiac surgery in the incidence of VT recurrence after VT substrate ablation. Furthermore, in order to assess this potential relationship, the antecedent of prior cardiac surgery was included in the univariate analysis and, according to this study’s data, it was not related with the occurrence of VT recurrence [HR 0.937(0.342.58); p=0.937] (table 3). A recent study has shown that epicardial substrate can be eliminated by endocardial ablation
29
. However, the same study also reported that
complete elimination of epicardial substrate was achieved in only a minority of ischemic cases (22.2%); therefore, the majority of them would require an epicardial ablation to completely eliminate the epicardial substrate
29
. In addition to this and
according to the present study data, patients with transmural MI who underwent only endocardial ablation are at an increased risk of VT recurrence, despite the potential impact of the endocardial ablation in the epicardial substrate. Thus, an epicardial approach should probably be considered in this group of patients in order to achieve complete substrate elimination and decrease VA episodes during follow-up.
Clinical Implications To date, there are no uniform criteria to decide on the need and the appropriate timing of an epicardial approach in post-MI VT substrate ablation procedures. Strategies based on systematic endo-epicardial mapping and ablation often fail to identify epicardial substrate
12, 13
. This could be avoided by appropriate identification of patients with
potential arrhythmogenic substrate located at the epicardium. Currently available cardiac imaging techniques such as ce-CMR, echocardiography, CT, and SPECT have been shown to appropriately assess MI extent and transmurality. Consistently, and in light of the results of the present study (better outcomes with endo-epicardial ablation in
17
patients with transmural MI), complete substrate accessibility should be pursued when attempting substrate ablation for post-MI VT, meaning that an epicardial approach should be considered in patients with evidence of IT.
Limitations This study could not determine whether the higher incidence of VT recurrence observed in patients with transmural MI and an endocardial-only approach compared to those with endo-epicardial approach is exclusively due to complete substrate accessibility or might involve other uncontrolled conditions not taken into account in this study. A randomized controlled trial comparing endo-epicardial vs endocardial-only approach in patients with transmural MI would be needed to address this question. Additionally, it remains unknown whether more extensive ablation strategies may yield better results. In order to answer this question properly, a randomized trial comparing scar dechanneling vs more extensive ablation techniques would be required. Conclusions An exclusively endocardial approach in patients with transmural MI undergoing VT substrate ablation may be associated with an increased risk of recurrence. IT may be a useful criterion in the decision to choose a combined endo-epicardial approach in postMI VT susbtrate ablation procedures. The proportion of patients meeting transmurality criteria was significantly higher in the group assessed by ce-CMR vs other imaging techniques.
Disclosures None
18
References 1.
Reddy VY, Reynolds MR, Neuzil P, Richardson AW, Taborsky M, Jongnarangsin K, Kralovec S, Sediva L, Ruskin JN, Josephson ME. Prophylactic Catheter Ablation for the Prevention of Defibrillator Therapy. New England Journal of Medicine 2007;357:2657-2665.
2.
Kuck KH, Schaumann A, Eckardt L, Willems S, Ventura R, Delacrétaz E, Pitschner H-F, Kautzner J, Schumacher B, Hansen PS, group ftVs. Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary heart disease (VTACH): a multicentre randomised controlled trial. The Lancet Feb 02 2010;375:31-40.
3.
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 Dec 16 2008;118:2773-2782.
4.
Sacher F, Tedrow UB, Field ME, Raymond J-M, Koplan BA, Epstein LM, Stevenson WG. Ventricular Tachycardia Ablation: Evolution of Patients Over 8 Years. Circulation: Arrhythmia and Electrophysiology August 1, 2008 2008;1:153-161.
5.
Fernandez-Armenta J, Berruezo A, Andreu D, et al. Three-Dimensional Architecture of Scar and Conducting Channels Based on High Resolution ceCMR: Insights for Ventricular Tachycardia Ablation. Circulation: Arrhythmia and Electrophysiology Jul 18 2013;6:528-537.
6.
Sosa E, Scanavacca M, D'Avila A, Pilleggi E. A New Technique to Perform Epicardial Mapping in the Electrophysiology Laboratory. Journal of Cardiovascular Electrophysiology 1996;7:531-536.
19
7.
Sosa E, Scanavacca M, D'Avila A, Piccioni J, Sanchez O, Velarde JL, Silva M, Reolao B. Endocardial and epicardial ablation guided by nonsurgical transthoracic epicardial mapping to treat recurrent ventricular tachycardia. J Cardiovasc Electrophysiol Mar 1998;9:229-239.
8.
Berruezo A, Fernandez-Armenta J, Mont L, Zeljko H, Andreu D, Herczku C, Boussy T, Tolosana JM, Arbelo E, Brugada J. Combined Endocardial and Epicardial Catheter Ablation in Arrhythmogenic Right Ventricular Dysplasia Incorporating Scar Dechanneling Technique. Circ Arrhythm Electrophysiol Mar 01 2012;5:111-121.
9.
Cano O, Hutchinson M, Lin D, Garcia F, Zado E, Bala R, Riley M, Cooper J, Dixit S, Gerstenfeld E, Callans D, Marchlinski FE. Electroanatomic Substrate and Ablation Outcome for Suspected Epicardial Ventricular Tachycardia in Left Ventricular Nonischemic Cardiomyopathy. J Am Coll Cardiol Aug 25 2009;54:799-808.
10.
Schmidt B, Chun KRJ, Baensch D, Antz M, Koektuerk B, Tilz RR, Metzner A, Ouyang F, Kuck KH. Catheter ablation for ventricular tachycardia after failed endocardial ablation: Epicardial substrate or inappropriate endocardial ablation? HRTHM Dec 01 2010;7:1746-1752.
11.
Jais P, Maury P, Khairy P, et al. Elimination of Local Abnormal Ventricular Activities: A New End Point for Substrate Modification in Patients With ScarRelated Ventricular Tachycardia. Circulation Jun 07 2012;125:2184-2196.
12.
Di Biase L, Santangeli P, Burkhardt DJ, et al. Endo-Epicardial Homogenization of the Scar Versus Limited Substrate Ablation for the Treatment of Electrical Storms in Patients With Ischemic Cardiomyopathy. J Am Coll Cardiol
Jul 10 2012;60:132-141.
20
13.
Tung R, Michowitz Y, Yu R, Mathuria N, Vaseghi M, Buch E, Bradfield J, Fujimura O, Gima J, Discepolo W, Mandapati R, Shivkumar K. Epicardial ablation of ventricular tachycardia An institutional experience of safety and efficacy. Heart Rhythm Apr 20 2013;10:490-498.
14.
Cerqueira MD. Standardized Myocardial Segmentation and Nomenclature for Tomographic Imaging of the Heart: A Statement for Healthcare Professionals From the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation Feb 29 2002;105:539-542.
15.
Alexandre J, Saloux E, Dugu AE, Lebon A, Lemaitre A, Roule V, Labombarda F, Provost N, Gomes S, Scanu P, Milliez P. Scar extent evaluated by late gadolinium enhancement CMR: a powerful predictor of long term appropriate ICD therapy in patients with coronary artery disease. Journal of Cardiovascular Magnetic Resonance Feb 19 2013;15:1-1.
16.
Faletra F, Crivellaro W, Pirelli S, Parodi O, De Chiara F, Cipriani M, Corno R, Pezzano A. Value of transthoracic two-dimensional echocardiography in predicting viability in patients with healed Q-wave anterior wall myocardial infarction. Am J Cardiol Nov 15 1995;76:1002-1006.
17.
Cwajg JM, Cwajg E, Nagueh SF, He ZX, Qureshi U, Olmos LI, Quinones MA, Verani MS, Winters WL, Zoghbi WA. End-diastolic wall thickness as a predictor of recovery of function in myocardial hibernation: relation to restredistribution T1-201 tomography and dobutamine stress echocardiography. J Am Coll Cardiol Apr 2000;35:1152-1161.
18.
Mele D, Agricola E, Galderisi M, Rigo F, Citro R, Dal Monte A, Della Valentina P, Calabrese A, Ferrari R. Echocardiographic myocardial scar burden predicts response to cardiac resynchronization therapy in ischemic heart failure.
21
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography Jun 2009;22:702-708. 19.
Tian J, Jeudy J, Smith MF, et al. Three-Dimensional Contrast-Enhanced Multidetector CT for Anatomic, Dynamic, and Perfusion Characterization of Abnormal Myocardium To Guide Ventricular Tachycardia Ablations. Circ Arrhythm Electrophysiol Oct 19 2010;3:496-504.
20.
Dickfeld T, Lei P, Dilsizian V, Jeudy J, Dong J, Voudouris A, Peters R, Saba M, Shekhar R, Shorofsky S. Integration of Three-Dimensional Scar Maps for Ventricular Tachycardia Ablation With Positron Emission TomographyComputed Tomography. JACC: Cardiovasc Imaging Feb 2008;1:73-82.
21.
Cochet H, Komatsu Y, Sacher F, et al. Integration of Merged Delayed-Enhanced Magnetic Resonance Imaging and Multidetector Computed Tomography for the Guidance of Ventricular Tachycardia Ablation: A Pilot Study. J Cardiovasc Electrophysiol Dec 17 2012;24:419-426.
22.
Stolzmann P, Scheffel H, Leschka S, Schertler T, Frauenfelder T, Kaufmann PA, Marincek B, Alkadhi H. Reference values for quantitative left ventricular and left atrial measurements in cardiac computed tomography. European radiology Aug 2008;18:1625-1634.
23.
Arenal A, del Castillo S, Gonzalez-Torrecilla E, Atienza F, Ortiz M, Jimenez J, Puchol A, Garcia J, Almendral J. Tachycardia-related channel in the scar tissue in patients with sustained monomorphic ventricular tachycardias: influence of the voltage scar definition. Circulation Oct 26 2004;110:2568-2574.
24.
Berruezo A, Fernandez-Armenta J, Andreu D, et al. Scar dechanneling: a new method for scar-related left ventricular tachycardia substrate ablation. Circ Arrhythm Electrophysiol Apr 2015;8:326-336.
22
25.
Fernández-Armenta J, Andreu D, Penela D, Trucco E, Cipolletta L, Arbelo E, Berne P, Tolosana JM, Pedrote A, Brugada J, Mont L, Berruezo A. Sinus rhythm detection of conducting channels and ventricular tachycardia isthmus in arrhythmogenic right ventricular cardiomyopathy. Heart Rhythm Jun 01 2014;11:747-754.
26.
Sacher F, Roberts-Thomson K, Maury P, et al. Epicardial Ventricular Tachycardia Ablation: A Multicenter Safety Study. J Am Coll Cardiol May 25, 2010 2010;55:2366-2372.
27.
Sarkozy A, Tokuda M, Tedrow UB, Sieira J, Michaud G, Couper GS, John R, Stevenson WG. Epicardial Ablation of Ventricular Tachycardia in Ischemic Heart Disease. Circ Arrhythm Electrophysiol Oct 09 2013;6:1115-1122.
28.
Andreu D, Ortiz-Perez JT, Boussy T, Fernandez-Armenta J, De Caralt TM, Perea RJ, Prat-Gonzalez S, Mont L, Brugada J, Berruezo A. Usefulness of contrast-enhanced cardiac magnetic resonance in identifying the ventricular arrhythmia substrate and the approach needed for ablation. Eur Heart J Feb 06 2014;35:1316-1326.
29.
Komatsu Y, Daly M, Sacher F, et al. Endocardial Ablation to Eliminate Epicardial Arrhythmia Substrate in Scar-Related Ventricular Tachycardia. J Am Coll Cardiol May 15 2014;63:1416-1426.
23
Clinical Perspectives To date, there is no consensus on the need and appropriate timing of epicardial ablation in post-infarction VT substrate ablation. The present study provides useful information for the selection of patients that could be candidate for first-line endoepicardial approach. Firstly, a high proportion of patients (87.5%) with transmural scar identified by means of routinely used imaging techniques had epicardial arrhythmic substrate, which indicates that infarct transmurality correctly identified patients requiring epicardial approach to completely eliminate this arrhythmogenic substrate. Secondly, the study shows that patients with transmural infarction who undergo an exclusively endocardial approach during VT substrate ablation procedures are at an increased risk of VT/VF recurrence. Therefore, according to the results of this study, infarct transmurality could be assessed and used to decide on the approach needed when the ablation procedure is aimed to completely eliminate the arrhythmic substrate. Randomized controlled trials comparing endo-epicardial vs endocardial-only approach in patients with transmural infarction would be needed to clarify the benefit of first line endo-epicardial approach for VT substrate ablation procedures.
Figure 1. Infarct transmurality criteria in an anterior myocardial infarction. A, Magnetic resonance images showing an apical left ventricular aneurysm and a transmural anterosepto-apical myocardial hyperenhancement (yellow arrow). B, Echocardiography: 4chamber view showing an aneurismatic left ventricle and apical wall thinning. C, Electroanatomic bipolar maps (left anterior oblique views) of endocardial and epicardial left ventricle surface, showing low voltage areas in segments that exhibited transmurality criteria in both ce-CMR and echocardiography. Electrograms with sequential activation pattern can be observed in endocardium and epicardium.
Figure 2. Infarct transmurality criteria in an inferoposterior myocardial infarction. A, Magnetic resonance images showing a transmural inferoposterior myocardial hyperenhancement (yellow arrows). B, Computed tomography showing basal
24
inferoposterior wall thinning. C, Electroanatomic bipolar maps (left anterior oblique views) of endocardial and epicardial left ventricle surface, showing low-voltage areas in segments that exhibited transmurality criteria in both ce-CMR and computed tomography. Electrograms with sequential activation pattern can be observed in endocardium and epicardium.
Figure 3. Study Flow Chart. MI, myocardial infarction; VT, ventricular tachycardia.
Figure 4. Kaplan-Meier curve for the endpoint of ventricular tachycardia recurrence according to infarct transmurality and type of approach. Group 1: patients with subendocardial infarction and endocardial approach. Group 2: patients with transmural infarction and endo-epicardial approach. Group 3: patients with transmural infarction and endocardial approach. VT=ventricular tachycardia.
25
Table
1.
Baseline
Clinical
Characteristics.
Group
1,
subendocardial
infarction/endocardial approach; Group 2, transmural infarction/endo-epicardial approach; Group 3. transmural infarction/endocardial approach. Group 1
Group 2
Group 3
(N=34)
(N=24)
(N=32)
Age, yrs
66.8±11.6
67.8±10.2
67.1±8.8
0.913
Follow-up, months
24.8±13.5
17.5±12.3
23.8±14.5
0.112
Hypertension
30 (88.2%)
18 (75%)
25 (78.1%)
0.289
ICD
28 (82.4%)
24 (100%)
28 (87.5%)
0.096
NYHA ≥III
6 (17.6%)
3 (12.5%)
6 (18.7%)
0.749
33.4±12
34.6±7.7
31±12
0.297
-1
15 (48.4%)
11 (45.8%)
8 (25%)
-2
6 (19.4%)
5 (20.8%)
8 (25%)
-3
6 (19.4%)
3 (12.5%)
14 (43.7%)
Class III
23 (67.6%)
12 (50%)
16 (50%)
0.252
Prior PCI
17 (50%)
13 (54.1%)
21 (65.5%)
0.745
Prior Cardiac
7 (21.2%)
0 (0%)
14 (46.8%)
0.011
LVEF, %
p value
Diseassed vessels
0.135
Surgery - CABG - CABG + valve - Valve Time from MI, yrs
6 (17.6%)
13 (40.6%)
0
1 (3.1%)
1 (2.9%)
0
16.4±7.9
18.6±9.8
14.9±10.1
- Anterior/Apical
15 (45.4%)
10 (45.8%)
11 (34.3%)
- Inferior
18 (52.9%)
12 (50%)
20 (62.5%)
- Lateral
1 (2.9%)
1 (4.2%)
1 (3.1%)
0.359
Scar localisation
0.913
26
Abbreviations: AAD, antiarrhythmic drugs; ICD, implantable cardioverter defibrillator; NYHA, New York Heart Association; LVEF, left ventricular ejection fraction; PCI, percutaneous coronary intervention; MI, myocardial infarction
27
Table 2. Substrate Mapping Data: Comparison by Procedure Type. Group 1, subendocardial infarction/endocardial approach; Group 2, transmural infarction/endoepicardial approach; Group 3, transmural infarction/endocardial approach. Group 1
Group 2
Group 3
(N=34)
(N=24)
(N=32)
521±202.9
473.5±158.4
---
478.6±257.5
---
60.4± 33.2
63.5±34.6
72.4±34.1
---
48.2±31.6
---
- endocardial
57.1±31,5
73.8±31.5
75.7±45.3
- endocardial
---
46.3±25.9
---
23.5±15.4
18.2±10.8
27.6±15.1
--
7.7±7.2
---
32 (94.1%)
20(83.3%)
25(78.1%)
p value
No of points - endocardial - epicardial
553.4±205.2 0.335 n/a
Scar area < 1.5 mV (cm2) - endocardial - epicardial
0.465 n/a
No of E-DCs 0.096 n/a
No of RF applications - endocardial - epicardial
Complete CC-EG elimination
0.065 n/a
0.170
(%)
Abbreviations: Endo-Endo, subendocardial scar with endocardial approach; TransEndo, transmural scar with endocardial approach; Trans-Endo/Epi, transmural scar with endo-epicardial approach; N values, number of procedures; CC-EG, conducting channel electrogram; E-DC, electrogram with delayed component; RF, radiofrequency.
28
Table 3. Univariate and Multivariate Cox Regression Analysis for the Association Between Clinical and Procedure-related Variables for the Study Endpoint (VT Recurrence). Univariate
P
HR (95%CI)
Multivariate
P
HR (95%CI)
Age
1.03(0.98-1.07)
0.270
LVEF
0.99(0.96-1.03)
0.664
Heart failure
1.79(0.65-4.91)
0.259
Prior Cardiac Surgery
0.93(0.34-2.58)
0.937
ICD
1.06(0.31-3.60)
0.928
Class I
1.84(0.54-6.29)
0.330
Class III
1.45(0.59-3.52)
0.412
1.73(0.61-4.18)
0.225
0.99(0.99-1.01)
0.888
VT/VF 2.81(1.18-6.66)
0.019
AAD
Arrhythmic Storm/Incessant VT Clinical VT CL End-procedure
3.05(1.27-7.35)
0.013
inducibility Endo Scar area <1,5 mV 1(0.99-1.02)
0.742
(cm2) Number of EG-DC Radiofrequency
1.01(0.99-1.02)
0.181
ablation 1(0.99-1.01)
0.166
EG-DC 0.99(0.97-1.01)
0.743
time Number
of
(remap) Type of Approach - Endo-Endo
1
- Transmural-Endo/Epi
1.85(0.43-8.00)
0.410
1.49(0.34-6.49)
0.599
- Transmural-Endo
3.89(1.38-11.00)
0.01
4.03(1.42-11.43)
0.009
30
31
32
33
34
Infarct Transmurality as a Criterion for First-Line Endo-Epicardial Substrate-Guided Ventricular Tachycardia Ablation in Ischemic Cardiomyopathy Juan Acosta MD, Juan Fernández-Armenta MD, Diego Penela MD, David Andreu MSc, PhD, Roger Borras MSc, Francesca Vassanelli MD, Viatcheslav Korshunov MD, Rosario J Perea MD, PhD, Teresa M de Caralt MD, PhD, Jose T Ortiz MD, PhD, Guillermina Fita MD, PhD, Marta Sitges MD, PhD, Josep Brugada MD, PhD, Lluis Mont MD, PhD, Antonio Berruezo MD, PhD
PII: DOI: Reference:
S1547-5271(15)00892-9 http://dx.doi.org/10.1016/j.hrthm.2015.07.010 HRTHM6353
To appear in:
Heart Rhythm
www.elsevier.com/locate/buildenv
Cite this article as: Juan Acosta MD, Juan Fernández-Armenta MD, Diego Penela MD, David Andreu MSc, PhD, Roger Borras MSc, Francesca Vassanelli MD, Viatcheslav Korshunov MD, Rosario J Perea MD, PhD, Teresa M de Caralt MD, PhD, Jose T Ortiz MD, PhD, Guillermina Fita MD, PhD, Marta Sitges MD, PhD, Josep Brugada MD, PhD, Lluis Mont MD, PhD, Antonio Berruezo MD, PhD, Infarct Transmurality as a Criterion for First-Line Endo-Epicardial Substrate-Guided Ventricular Tachycardia Ablation in Ischemic Cardiomyopathy, Heart Rhythm, http://dx.doi.org/10.1016/j. hrthm.2015.07.010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Infarct Transmurality as a Criterion for First-Line EndoEpicardial Substrate-Guided Ventricular Tachycardia Ablation in Ischemic Cardiomyopathy Short Title: Infarct Transmurality and Endo-Epi VT Ablation
Juan Acosta, MD1; Juan Fernández-Armenta MD1, Diego Penela, MD1; David Andreu, MSc, PhD1; Roger Borras, MSc1; Francesca Vassanelli, MD1; Viatcheslav Korshunov, MD1; Rosario J Perea, MD, PhD2; Teresa M de Caralt, MD, PhD2, Jose T Ortiz, MD, PhD1, Guillermina Fita, MD, PhD1; Marta Sitges, MD, PhD1, Josep Brugada, MD, PhD1; Lluis Mont, MD, PhD1; Antonio Berruezo, MD, PhD1
1
Arrhythmia Section, Cardiology Department, Thorax Institute, Hospital Clínic and IDIBAPS (Institut d’Investigació Agustí Pi i Sunyer), Barcelona, Catalonia, Spain 2
Radiology Department, Hospital Clinic, University of Barcelona, Barcelona, Catalonia, Spain
Conflict of Interest: All authors have no conflict of interest to declare.
Address for Correspondence: Antonio Berruezo, MD, PhD Arrhythmia Section, Cardiology Department. Thorax Institute, Hospital Clinic C/ Villarroel 170 08036 Barcelona Phone: 0034 93 2275551 Fax: 0034 93 4513045
1
Email: [email protected]
Abstract Background: There is no consensus on the appropriate indications for epicardial approach in substrate ablation of post-myocardial infarction (MI) ventricular tachycardia (VT). Objective: Infarct transmurality (IT) could identify patients that would benefit from a combined first-line endo-epicardial approach. Methods: Before ablation, IT was assessed by contrast-enhanced magnetic resonance imaging (hyperenhancement ≥75% of wall thickness in ≥1 segment), echocardiography (dyskinesia/akinesia + hyperrefringency + wall-thinning), computer tomography (wall thinning), or scintigraphy (transmural necrosis). Prospectively from January 2011, endocardial approach was used in patients with subendocardial MI (group 1) and combined endo-epicardial approach in patients with transmural MI (group 2). Outcomes in both groups were compared with patients with transmural MI and only endocardial approach due to prior cardiac surgery or procedure performed before January 2011 (group 3). Primary endpoint was VT/VF recurrence-free survival. Results: Ninety patients (92.2% men, 67.4±9.8 years) undergoing VT substrate ablation were included: group 1, N=34; group 2, N=24; group 3, N=32. During a mean followup of 22.5±13.7 months, 5 patients in group 1 (14.7%), 3 patients in group 2 (12.5%) and 13 patients in group 3 (40.6%) had VT recurrences; p=0.011. Time to recurrence was shortest in group 3 (log-Rank p=0.018). Endocardial approach in patients with transmural MI was associated with an increased risk of recurrence (hazard ratio 4.01; 95%CI 1.41-11.3; p=0.009). Conclusion: Endocardial approach in patients with transmural MI undergoing VT substrate ablation is associated with an increased risk of recurrence. IT may be a useful criterion in the decision to choose a first-line combined endo-epicardial approach.
Key Words: Infarct Transmurality. Epicardial Approach. Ventricular Tachycardia Ablation.
2
Abbreviation List CC: conducting channel. ce-CMR: contrast-enhanced cardiac magnetic resonance. Ce-MDCT: contrast-enhanced multidetector computed tomography. EAM: electroanatomic map. E-DC: electrogram with delayed component. IT: infarct transmurality. LV: left ventricle. MI: myocardial infarction. RF: radiofrequency. VF: ventricular fibrillation. VT: ventricular tachycardia.
Introduction Substrate-based catheter ablation is an effective therapeutic option in patients with recurrent episodes of scar-related ventricular tachycardia (VT)
1, 2
. However, data
obtained from large series of patients reveal that prevention of VT recurrence is not achieved after conventional endocardial ablation in a significant proportion of patients 3, 4
. In the case of ischemic cardiomyopathy, VT recurrences after endocardial substrate
ablation might be due to the persistence of epicardial circuits in some cases. A recent study has shown that 63% of patients with post-myocardial infarction (MI) transmural scar exhibit epicardial border zone channels 5. Therefore, epicardial substrate could play an important role in this subgroup of ischemic patients. Since its description by Sosa et al 6, epicardial ablation of VT has been shown to be beneficial in several clinical scenarios such as Chagas disease 7, right ventricular dysplasia
8
, and nonischemic cardiomyopathy
9
. However, due to its technical
complexity and potential risks, it is usually restricted to patients with previous failed endocardial ablation attempts 10.
3
A recent study has shown that complete VT substrate elimination is related to better clinical outcomes after ablation
11
. Therefore, ablation strategies that pursue complete
substrate accessibility may better achieve complete VT substrate elimination and improve current results of post-MI VT ablation. In addition, there is no consensus on the appropriate timing of epicardial approach in post-MI VT substrate ablation procedures. Studies by Di Biase et al and Tung et al have proposed that the endoepicardial approach in post-MI VT ablation, either as a first-line strategy or after failed endocardial ablation, is associated with improved clinical outcomes
12, 13
. However, in
these studies a significant proportion (27% and 67%, respectively) of patients who underwent epicardial mapping did not exhibit epicardial arrhythmogenic substrate. Therefore, criteria that better identify patients requiring epicardial mapping and ablation are needed. We hypothesized that complete substrate accessibility predicts long-term outcomes of post-MI VT substrate ablation and that infarct transmurality (IT) could support the appropriate selection of patients that will benefit from an endo-epicardial approach.
Methods Study Population Consecutive post-MI patients (N=90) referred for catheter ablation of documented infarct-related sustained monomorphic VT from November 2009 to February 2015 were included. The study complies with de Declaration of Helsinki. The local Ethics Committee approved the study protocol, and all included participants signed the informed consent.
4
Infarct Transmurality Assessment Prior to the ablation procedure, IT was assessed in all patients by at least one of the following methods: contrast-enhanced cardiac magnetic resonance (ce-CMR), echocardiography, iodine-enhanced multidetector computed tomography (MDCT) or cardiac single photon emission computed tomography (SPECT). According to the imaging technique performed, IT was assessed as follows: a) Patients with prior ce-CMR. In all patients without claustrophobia or classical contraindications for magnetic resonance (n=41; 45.6%), a preprocedural ce-CMR study was performed in a 3T scanner (Magnetom Trio-Tim, Siemens, Erlangen, Germany). Contrast-enhanced images were acquired 7 minutes after bolus injection of 0.2 mmol/kg Gadobutrol (Gadoyist, Bayer Hispania, Barcelona, Spain) using a commercially available, freebreathing,
ECG-gated,
navigator-gated,
3D
inversion-recovery,
gradient-echo
technique. The ce-CMR images were analyzed by experienced cardiologists and radiologists to depict the presence of scarred tissue for each left ventricle (LV) according to the 17-segment model 14. According to previous descriptions, the presence of hyperenhancement involving ≥75% of wall thickness was defined as transmural MI 15
.
b) Patients without prior ce-CMR In patients who could not undergo ce-CMR due to classical contraindications (N=49; 54.4%), definition of IT required the presence of transmurality criteria in at least 1 of the following imaging techniques: Echocardiography A preprocedural comprehensive transthoracic echocardiography was performed. Twodimensional echocardiographic images were obtained from the standard parasternal,
5
apical, and subcostal views. According to previous publications
16-18
, scar segments
were assumed to have lost most of their muscle fibers and be mainly composed of connective tissue if they showed all of the following echocardiographic patterns: 1) a reduction in end-diastolic wall thickness ≤ 0.5 cm; 2) hyperrefringency; and 3) akinesia or dyskinesia. This echocardiographic pattern was judged as being consistent with transmural scar segments (Figure 1, panels A-C). Echocardiograms were performed by experienced operators and were reviewed by two experienced observers in order to define the presence of infarct transmurality criteria. Contrast-enhanced MDCT (ce-MDCT) Preprocedural ECG-gated ce-MDCT was performed on a 128-slice CT scanner (Somatom Definition Flash, Siemens Healthcare, Erlangen, Germany). Images were acquired during an inspiratory breath-hold with tube current modulation set on enddiastole. CT angiographic images were acquired during the injection of a 180 mL bolus of Iopromide 370 mg I/mL (Ultravist, Bayer Hispania, Barcelona, Spain) at a rate of 5 mL/s. As has been reported 19-21, wall thinning at ce-MDCT correlates with low voltages areas in electroanatomic maps (EAM). According to this, and based on reference values of LV wall thickness
22
, two criteria were used to define IT by ce-MDCT: 1) wall
thickness ≤5 mm; and 2) presence of aneurysm (Figure 2, panels A-C). SPECT performed within 6 months before procedure A standard stress SPECT was performed using a 1-day protocol with 2-metoxil-isobutilisonitrila-99mTC. In a semicircular orbit from the right anterior oblique to the left posterior oblique projections, 64 views were obtained using a dual-head gammacamera. Tomograms were displayed as short-axis and horizontal and vertical long-axis slices, and as quantitative polar maps. These images were analyzed to depict nonviable myocardial segments. The presence of an irreversible perfusion defect with an extension
6
>75% of myocardial wall thickness was considered to be consistent with a transmural MI.
Electrophysiology Study and Substrate Mapping The electrophysiology study was performed under conscious sedation. An endocardial high-density, 3D, electroanatomic, bipolar voltage map of the LV was obtained during stable sinus rhythm using the CARTO system (Biosense, Inc, Diamond Bar, CA). Standard voltage thresholds (<0.5 mV for the core and <1.5 mV for the border zone) were used to define the scar on the EAM. The conducting channels (CCs) on the EAM were identified as either voltage channels, corridors of border zone within scar core areas or between a core area and the mitral annulus (identification was facilitated by voltage scanning of the upper and lower voltage thresholds) 23 or late potential channels, defined as ≥2 consecutive electrograms with delayed components (E-DCs) localized in the scar area, connecting with healthy tissue, impossible to visualize with a voltage threshold modification, and showing an activation sequence of the delayed component 8, 24
. In order to facilitate mapping, CCs were not always tracked all along their trajectory.
Instead, E-DCs were tagged and dichotomously classified as entrance or inner CC points, depending on delayed-component precocity during sinus rhythm. The CC entrance was defined as the E-DC with the shortest delay between the far-field component of healthy/border zone muscle (low frequency, usually high voltage) and the local component (delayed, high frequency, usually fractionated and low voltage) corresponding to the local activation of myocardial fibers in the scar. To avoid targeting healthy tissue beyond the scar area, CC entrances were tagged in a zone with 0.5-1.5 mV voltage 8, 24.
7
Epicardial Approach Beginning in January 2011, a first-line endo-epicardial approach was performed in all patients with transmural MI and no previous cardiac surgery. Percutaneous pericardial puncture was performed as described by Sosa et al using the subxiphoid approach 6. Epicardial mapping was performed similar to the endocardial mapping described above.
VT Ablation All patients underwent substrate-guided ablation using the “scar dechanneling” technique
8, 24
. Thus, radiofrequency (RF) energy was delivered at the previously
identified CC entrances as previously described
24, 25
. A change in the CC activation
sequence of the delayed components, or their disappearance during RF application, indicated a CC entrance block. These changes were detected by continuously recording local activation in the CC with the proximal dipoles of the ablation catheter or by a remap of the scar area. RF ablation was performed with a Navistar catheter (Biosense Webster) and was controlled by a temperature limit of 45ºC with a power limit of 50W at the endocardium and 40-50W at the epicardium. The catheter irrigation rate during RF application was 26 mL/min in the endocardium and 17 mL/min in the epicardium. Coronary arteries were localized through the integration of CT/CMR into the navigation system. Phrenic nerve course was obtained by high-output epicardial pacing. A postablation remap was always performed to document the elimination of all the CCelectrograms and to eliminate the remaining E-DCs by back-up RF applications. Clinical and nonclinical induced VTs after scar dechanneling were targeted for ablation. VT isthmus and exit sites were defined by entrainment mapping if the VT was tolerated and by pace mapping if not tolerated.
8
Patient Groups According to the type of approach (endocardial vs endo-epicardial) and IT (transmural vs no transmural MI), patients were classified by substrate accessibility to permit complete substrate ablation: Group 1, nontransmural MI and only endocardial approach; Group 2, transmural MI and endo-epicardial approach; Group 3 (incomplete substrate accessibility), transmural MI and only endocardial approach, due to prior cardiac surgery and procedure performed before January 2011.
Procedural Success and Follow Up Acute success was defined as noninducibility of any monomorphic VT at the end of the procedure. Partial success was considered when the clinical VT was successfully ablated but other monomorphic VTs remained inducible. Office visits for clinical evaluation and ICD interrogation were scheduled every 6 months. The primary endpoint was the occurrence of VT or ventricular fibrillation (VF). Any sustained VT, whether or not ICD intervention was required, and any VF episode were considered a recurrence during follow-up. The secondary endpoint was all-cause mortality.
Statistical Analysis Continuous variables are presented as mean ± standard deviation. To compare means of two variables the Student’s t test, Mann-Whitney U test or Anova test were used as appropriate. Categorical variables were expressed as total number (percentages) and compared between groups using Chi-square test. Kaplan-Meier survival analysis was used to analyze the time to VT recurrence and redo, and log-rank test was used to detect significant differences among groups. The baseline clinical characteristics, recurrence and mortality were analyzed by including each patient only once in either group (per
9
patient analysis) The effect of different variables on (event-free) survival was investigated using the Cox proportional hazards model. Variables that showed a statistically significant effect on (event-free) survival in univariate analyses were entered in a multivariate Cox proportional hazards model using a backward stepwise selection to obtain the final model. At each step, the least significant variable was discarded from the model, until all variables in the model reached a P-value below 0.10. The number of variables that could enter the multivariate was limited using the P,m/10 rule to prevent over-fitting the model. For all tests, a p value <0.05 was considered significant. Statistical analysis was performed using R software for Windows version 3.1.2 (R project for statistical computing; Vienna, Austria) and SPSS version 18.0 (SPSS, Inc, Chicago, IL)..
Results A total of 90 patients (92.2% men, 67.4±9.8 years) undergoing VT substrate ablation were included (Figure 3).
Infarct Transmurality and Patient Groups. A total of 41 patients (45.6%) underwent ce-CMR before ablation. Thirty-two of them (78%) exhibited transmural MI. In the remaining 49 patients, IT was assessed by echocardiography, ce-MDCT, or SPECT (Supplemental Table 1). Among them, 24 (49%) met transmurality criteria in at least one of the imaging techniques performed. As a result, non-transmural MI was found in 34 patients (37.8%) who underwent only an endocardial approach (group 1). The remaining 56 patients exhibited transmural MI before the procedure; 24 (26.7%) underwent the endo-epicardial approach (group 2) and 32 (35.6%) the endocardial approach (group 3). It should be noted that in the majority of patients in whom ce-CMR could not be performed, infarct transmurality assessment was based on two imaging techniques (CT+echo or echo+ SPECT). No cases of discordance between imaging techniques were observed using the criteria described
10
(Supplemental Table 1).
Baseline clinical characteristics are summarized in Table 1. No differences were found between groups.
Substrate Mapping In groups 1 and 3, patients underwent only endocardial mapping; in group 2, a combined endo-epicardial approach during sinus rhythm was performed. Epicardial access was attempted in 24 (26.6%) patients and achieved in 23 (95.8%). The epicardial approach was not successful during the first procedure in only 2 patients; a successful procedure with epicardial approach was performed 4 days later in one patient, and in the other a redo with surgical epicardial approach was performed due to recurrence. Data from these substrate maps are summarized in Table 2. A total of 34 procedures with endocardial approach were performed in group 1 patients, 26 procedures with endoepicardial approach in group 2 patients, and 32 procedures with endocardial approach in group 3 patients. No statistically significant differences in endocardial scar area were found between groups. However, transmural MIs (groups 2 and 3) presented a slightly higher number of E-DCs than subendocardial MIs, albeit nonsignificant (Table 2). All patients with IT criteria that underwent epicardial mapping (N=24) had low voltage areas in the epicardium, and 21 of them (87.5%) had arrhythmogenic substrate, expressed as E-DCs. The proportion of patients meeting transmurality criteria was significantly higher in the group assessed by ce-CMR (78%) vs IT assessment by echocardiography, ce-MDCT or SPECT (49%); p=0.004. Although no statistically significant differences in endocardial and epicardial scar areas were observed between these two patient groups, a tendency towards higher values of endocardial and epicardial scar areas and numbers of E-DC
11
was observed in patients with IT according to echocardiogram/ce-MDCT/SPECT assessment (Supplemental Table 2). This suggests that the transmurality criteria proposed for ce-CMR may be less rigorous than those defined for the other three imaging techniques.
VT ablation. Acute Results All patients underwent substrate ablation with the scar dechanneling technique: endocardial in groups 1 and 3 and endo-epicardial in group 2. Complete scar dechanneling could be achieved in 32 patients (94.1%) in group 1, 20 patients (83.3%) in group 2 and 25 patients (78.1%) in group 3; p=0.170. After substrate ablation, 73 inducible residual VTs were induced in 40 patients (44.4%). The rate of residual VT inducibility was similar in all three patient groups: 13 patients (38.2%) in group 1, 8 patients (33.3%) in group 2, and 15 patients (46.9%) in group 3; p=0.572. Sixty-six (90.4%) of these residual VTs were targeted for ablation, 42 guided by activation mapping and 24 by pacemapping. In procedures with an endo-epicardial approach, a total of 9 residual VTs were induced and 2 (22.2%) of them had an epicardial origin. After residual VT ablation, the noninducibility rate of monomorphic sustained VT increased from 55.5% to 80%. No differences in noninducibility rate were observed between groups: 29 patients (85.2%) in group 1, 22 patients (91.6%) in group 2, and 24 patients (75%) in group 3; p=0.235.
Procedure-Related Complications Nine patients (10%) presented complications related to the procedure: 3 in group 1 (8.8%), 5 in group 2 (20.8%), and 1 in group 3 (3.1%); p=0.08. Complications in group 1 consisted of 1 complete AV block, 1 femoral hematoma and 1 cardiac tamponade
12
after endocardial ablation requiring pericardiocentesis. Complications in group 2 consisted of 1 cardiac tamponade requiring pericardiocentesis, 1 complete AV block requiring CRT-ICD implantation, 1 case of phrenic nerve palsy, 1 hemothorax and 1 transient ischemic attack without sequela. It should be noted that in patients with an endo-epicardial approach, only 3 complications were potentially related to the epicardial approach. The only complication in group 3 was 1 transient ischemic attack without sequelae.
Follow-up Mean duration (±SD) of follow-up was of 22.5±13.7 months. During follow-up, antiarrhythmic treatment was maintained in 22 patients (24.4%): 11 patients in group 1 (32.3%), 2 in group 2 (8.3%) and 9 in group 3 (28.1%); p=0.083. Recurrences of sustained VT were observed in 21 (23.3%) patients. Of these, 7(33.3%) received ICD shock and 8 (38%) had VT episodes that were terminated by antitachycardia pacing. Five (23.8%) patients with VT episodes were monitored in the VT detection zone and did not receive any therapy. One (4.7%) patient without ICD due to comorbidities and low life expectancy experienced a VT recurrence that required an external shock. No recurrences of VF episodes were observed. Patients with incomplete substrate accessibility (group 3) showed a significantly higher event rate for the endpoint of VT recurrence: 40.6% vs 14.7% in group 1 and 12.5% in group 2; p=0.011. Additionally, Kaplan-Meier analysis showed a significantly lower VT/VF recurrence-free survival in group 3 patients (log-Rank p=0.018) (Figure 4). Table 3 shows univariate and multivariate Cox regression analysis results for the study endpoint. Univariate analysis identified an association between 2 variables and the primary endpoint: end-procedure VT/VF inducibility (HR 2.81 [1.18-6.66], p=0.019)
13
and endocardial approach in transmural MI (HR 3.89 [1.38-11], p=0.01). No association was found between antiarrhythmic treatment during follow-up and the primary endpoint [HR 0.43 (0.18-1.02), p=0.056]. The multivariate analysis revealed that both endprocedure VT/VF inducibility (HR 3.05 [1.27-7.35], p=0.013) and endocardial approach in transmural MI were independent predictors of a sustained ventricular arrhythmia episode (HR 4.03 [1.42-11.43], p=0.009). Four (4.4%) patients died during follow-up: 3 (75%) due to advanced heart failure and 1 (25%) due to noncardiac cause. No differences in mortality were observed between groups: 1 patient died in group 1 (2.9%), 1 in group 2 (4%), and 2 in group 3 (6.2%); p=0.789.
Redo procedures A redo procedure was performed in 7 (33.3%) of the 21 patients who reached the study endpoint. All of them had a transmural MI and had undergone a previous endocardial ablation (group 3), due to prior cardiac surgery in 1 case, failure of previous epicardial approach in 1 case (which required a surgical epicardial approach), and an ablation performed before January 2011 in 5 cases. Therefore, a redo with epicardial approach was performed in 6 cases, while in the patient with previous cardiac surgery a new procedure with only endocardial approach was performed. Findings of the redo procedures are summarized in Supplemental Table 3. Briefly, all patients with transmural MI who underwent epicardial mapping consistently showed an arrhythmogenic epicardial substrate.
14
Discussion The present study describes the feasibility and benefits that could be expected with this novel image-based decision strategy for choosing the approach (endocardial vs endoepicardial) that will lower the recurrence rate in post-MI VT substrate ablation procedures. The decision is based on the identification of IT with imaging techniques routinely used in clinical practice. The study showed that patients with transmural MI who undergo only endocardial ablation are at increased risk of VT recurrence. To date, there is no consensus about the appropriate timing of an epicardial approach in post-MI VT substrate ablation procedures. It has been proposed that the persistence of epicardial substrate might be an important cause of VT recurrence in patients who had undergone a previous endocardial ablation 10. This has led to suggestions of performing an epicardial approach in patients with prior failed attempts of endocardial ablation 27
. In studies by Tung et al
13
and Di Biase et al
26,
12
, the endo-epicardial approach has
been shown to improve outcomes in patients with post-MI VT after substrate ablation; however, epicardial ablation was not performed in a significant proportion of patients due to the absence of epicardial substrate. In the study by Di Biase et al, in which epicardial approach was performed systematically, epicardial substrate was found in only 33% of patients
12
, whereas Tung et al reported absence of epicardial targets in
26.4% of cases, in which an epicardial approach was performed due to previous failed endocardial ablation, intracardiac thrombus, or electrocardiographic criteria
13
. Thus,
according to these data, better criteria are needed to identify those patients with post-MI VT that could benefit from epicardial mapping and ablation. It has been recently shown that the presence and distribution of scar provides useful clinical information to localize the target ablation substrate of VT. Andreu et al reported that the presence of epicardial hyperenhancement in any segment identified an
15
epicardial origin of the clinical VT with a high sensitivity and specificity
28
.
Additionally, it has been shown that a significant proportion of patients with transmural MI exhibit epicardial border zone channels 5. In the present study, epicardial approach was performed only if a transmural MI was observed in preprocedural cardiac imaging techniques. As a result, 87.5% of the patients that underwent epicardial mapping had an arrhythmogenic substrate, suggesting that the presence of a transmural MI correctly identifies those patients with potentially arrhythmogenic epicardial substrate. It should be noted that a tendency towards less epicardial substrate was observed in patients with IT according to ce-CMR, suggesting that it might be appropriate to define more rigorous transmurality criteria for ce-CMR for the specific purpose of deciding to perform an epicardial approach in post-MI patients undergoing VT substrate ablation. The major finding of the present study is that patients with transmural MI undergoing only endocardial ablation are at increased risk of VT recurrence. At the same time, no differences in the incidence of VT recurrence were found between patients with transmural
MI
who
underwent
endo-epicardial
ablation
and
patients
with
subendocardial MI in whom only an endocardial approach was performed. These results are consistent with the study by Jais et al, in which complete elimination of substrate was associated with a superior clinical outcome
11
. Thereby, substrate guided ablation
techniques, such as scar dechanneling, pursue complete substrate elimination under the assumption that substrate that is no related with clinical or inducible VTs at the moment of the procedure can activate and become a VT isthmus during follow-up. Therefore, the higher incidence of VT recurrence observed in patients with transmural MI and only endocardial approach could be due to the persistence of epicardial substrate. Given the differences observed in the requirement of CABG between groups 2 and 3, it could be argued that prior cardiac surgery could be associated with a higher incidence of VT
16
recurrence. However, to our best knowledge, there is no data about the potential role of prior CABG/cardiac surgery in the incidence of VT recurrence after VT substrate ablation. Furthermore, in order to assess this potential relationship, the antecedent of prior cardiac surgery was included in the univariate analysis and, according to this study’s data, it was not related with the occurrence of VT recurrence [HR 0.937(0.342.58); p=0.937] (table 3). A recent study has shown that epicardial substrate can be eliminated by endocardial ablation
29
. However, the same study also reported that
complete elimination of epicardial substrate was achieved in only a minority of ischemic cases (22.2%); therefore, the majority of them would require an epicardial ablation to completely eliminate the epicardial substrate
29
. In addition to this and
according to the present study data, patients with transmural MI who underwent only endocardial ablation are at an increased risk of VT recurrence, despite the potential impact of the endocardial ablation in the epicardial substrate. Thus, an epicardial approach should probably be considered in this group of patients in order to achieve complete substrate elimination and decrease VA episodes during follow-up.
Clinical Implications To date, there are no uniform criteria to decide on the need and the appropriate timing of an epicardial approach in post-MI VT substrate ablation procedures. Strategies based on systematic endo-epicardial mapping and ablation often fail to identify epicardial substrate
12, 13
. This could be avoided by appropriate identification of patients with
potential arrhythmogenic substrate located at the epicardium. Currently available cardiac imaging techniques such as ce-CMR, echocardiography, CT, and SPECT have been shown to appropriately assess MI extent and transmurality. Consistently, and in light of the results of the present study (better outcomes with endo-epicardial ablation in
17
patients with transmural MI), complete substrate accessibility should be pursued when attempting substrate ablation for post-MI VT, meaning that an epicardial approach should be considered in patients with evidence of IT.
Limitations This study could not determine whether the higher incidence of VT recurrence observed in patients with transmural MI and an endocardial-only approach compared to those with endo-epicardial approach is exclusively due to complete substrate accessibility or might involve other uncontrolled conditions not taken into account in this study. A randomized controlled trial comparing endo-epicardial vs endocardial-only approach in patients with transmural MI would be needed to address this question. Additionally, it remains unknown whether more extensive ablation strategies may yield better results. In order to answer this question properly, a randomized trial comparing scar dechanneling vs more extensive ablation techniques would be required. Conclusions An exclusively endocardial approach in patients with transmural MI undergoing VT substrate ablation may be associated with an increased risk of recurrence. IT may be a useful criterion in the decision to choose a combined endo-epicardial approach in postMI VT susbtrate ablation procedures. The proportion of patients meeting transmurality criteria was significantly higher in the group assessed by ce-CMR vs other imaging techniques.
Disclosures None
18
References 1.
Reddy VY, Reynolds MR, Neuzil P, Richardson AW, Taborsky M, Jongnarangsin K, Kralovec S, Sediva L, Ruskin JN, Josephson ME. Prophylactic Catheter Ablation for the Prevention of Defibrillator Therapy. New England Journal of Medicine 2007;357:2657-2665.
2.
Kuck KH, Schaumann A, Eckardt L, Willems S, Ventura R, Delacrétaz E, Pitschner H-F, Kautzner J, Schumacher B, Hansen PS, group ftVs. Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary heart disease (VTACH): a multicentre randomised controlled trial. The Lancet Feb 02 2010;375:31-40.
3.
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 Dec 16 2008;118:2773-2782.
4.
Sacher F, Tedrow UB, Field ME, Raymond J-M, Koplan BA, Epstein LM, Stevenson WG. Ventricular Tachycardia Ablation: Evolution of Patients Over 8 Years. Circulation: Arrhythmia and Electrophysiology August 1, 2008 2008;1:153-161.
5.
Fernandez-Armenta J, Berruezo A, Andreu D, et al. Three-Dimensional Architecture of Scar and Conducting Channels Based on High Resolution ceCMR: Insights for Ventricular Tachycardia Ablation. Circulation: Arrhythmia and Electrophysiology Jul 18 2013;6:528-537.
6.
Sosa E, Scanavacca M, D'Avila A, Pilleggi E. A New Technique to Perform Epicardial Mapping in the Electrophysiology Laboratory. Journal of Cardiovascular Electrophysiology 1996;7:531-536.
19
7.
Sosa E, Scanavacca M, D'Avila A, Piccioni J, Sanchez O, Velarde JL, Silva M, Reolao B. Endocardial and epicardial ablation guided by nonsurgical transthoracic epicardial mapping to treat recurrent ventricular tachycardia. J Cardiovasc Electrophysiol Mar 1998;9:229-239.
8.
Berruezo A, Fernandez-Armenta J, Mont L, Zeljko H, Andreu D, Herczku C, Boussy T, Tolosana JM, Arbelo E, Brugada J. Combined Endocardial and Epicardial Catheter Ablation in Arrhythmogenic Right Ventricular Dysplasia Incorporating Scar Dechanneling Technique. Circ Arrhythm Electrophysiol Mar 01 2012;5:111-121.
9.
Cano O, Hutchinson M, Lin D, Garcia F, Zado E, Bala R, Riley M, Cooper J, Dixit S, Gerstenfeld E, Callans D, Marchlinski FE. Electroanatomic Substrate and Ablation Outcome for Suspected Epicardial Ventricular Tachycardia in Left Ventricular Nonischemic Cardiomyopathy. J Am Coll Cardiol Aug 25 2009;54:799-808.
10.
Schmidt B, Chun KRJ, Baensch D, Antz M, Koektuerk B, Tilz RR, Metzner A, Ouyang F, Kuck KH. Catheter ablation for ventricular tachycardia after failed endocardial ablation: Epicardial substrate or inappropriate endocardial ablation? HRTHM Dec 01 2010;7:1746-1752.
11.
Jais P, Maury P, Khairy P, et al. Elimination of Local Abnormal Ventricular Activities: A New End Point for Substrate Modification in Patients With ScarRelated Ventricular Tachycardia. Circulation Jun 07 2012;125:2184-2196.
12.
Di Biase L, Santangeli P, Burkhardt DJ, et al. Endo-Epicardial Homogenization of the Scar Versus Limited Substrate Ablation for the Treatment of Electrical Storms in Patients With Ischemic Cardiomyopathy. J Am Coll Cardiol
Jul 10 2012;60:132-141.
20
13.
Tung R, Michowitz Y, Yu R, Mathuria N, Vaseghi M, Buch E, Bradfield J, Fujimura O, Gima J, Discepolo W, Mandapati R, Shivkumar K. Epicardial ablation of ventricular tachycardia An institutional experience of safety and efficacy. Heart Rhythm Apr 20 2013;10:490-498.
14.
Cerqueira MD. Standardized Myocardial Segmentation and Nomenclature for Tomographic Imaging of the Heart: A Statement for Healthcare Professionals From the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation Feb 29 2002;105:539-542.
15.
Alexandre J, Saloux E, Dugu AE, Lebon A, Lemaitre A, Roule V, Labombarda F, Provost N, Gomes S, Scanu P, Milliez P. Scar extent evaluated by late gadolinium enhancement CMR: a powerful predictor of long term appropriate ICD therapy in patients with coronary artery disease. Journal of Cardiovascular Magnetic Resonance Feb 19 2013;15:1-1.
16.
Faletra F, Crivellaro W, Pirelli S, Parodi O, De Chiara F, Cipriani M, Corno R, Pezzano A. Value of transthoracic two-dimensional echocardiography in predicting viability in patients with healed Q-wave anterior wall myocardial infarction. Am J Cardiol Nov 15 1995;76:1002-1006.
17.
Cwajg JM, Cwajg E, Nagueh SF, He ZX, Qureshi U, Olmos LI, Quinones MA, Verani MS, Winters WL, Zoghbi WA. End-diastolic wall thickness as a predictor of recovery of function in myocardial hibernation: relation to restredistribution T1-201 tomography and dobutamine stress echocardiography. J Am Coll Cardiol Apr 2000;35:1152-1161.
18.
Mele D, Agricola E, Galderisi M, Rigo F, Citro R, Dal Monte A, Della Valentina P, Calabrese A, Ferrari R. Echocardiographic myocardial scar burden predicts response to cardiac resynchronization therapy in ischemic heart failure.
21
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography Jun 2009;22:702-708. 19.
Tian J, Jeudy J, Smith MF, et al. Three-Dimensional Contrast-Enhanced Multidetector CT for Anatomic, Dynamic, and Perfusion Characterization of Abnormal Myocardium To Guide Ventricular Tachycardia Ablations. Circ Arrhythm Electrophysiol Oct 19 2010;3:496-504.
20.
Dickfeld T, Lei P, Dilsizian V, Jeudy J, Dong J, Voudouris A, Peters R, Saba M, Shekhar R, Shorofsky S. Integration of Three-Dimensional Scar Maps for Ventricular Tachycardia Ablation With Positron Emission TomographyComputed Tomography. JACC: Cardiovasc Imaging Feb 2008;1:73-82.
21.
Cochet H, Komatsu Y, Sacher F, et al. Integration of Merged Delayed-Enhanced Magnetic Resonance Imaging and Multidetector Computed Tomography for the Guidance of Ventricular Tachycardia Ablation: A Pilot Study. J Cardiovasc Electrophysiol Dec 17 2012;24:419-426.
22.
Stolzmann P, Scheffel H, Leschka S, Schertler T, Frauenfelder T, Kaufmann PA, Marincek B, Alkadhi H. Reference values for quantitative left ventricular and left atrial measurements in cardiac computed tomography. European radiology Aug 2008;18:1625-1634.
23.
Arenal A, del Castillo S, Gonzalez-Torrecilla E, Atienza F, Ortiz M, Jimenez J, Puchol A, Garcia J, Almendral J. Tachycardia-related channel in the scar tissue in patients with sustained monomorphic ventricular tachycardias: influence of the voltage scar definition. Circulation Oct 26 2004;110:2568-2574.
24.
Berruezo A, Fernandez-Armenta J, Andreu D, et al. Scar dechanneling: a new method for scar-related left ventricular tachycardia substrate ablation. Circ Arrhythm Electrophysiol Apr 2015;8:326-336.
22
25.
Fernández-Armenta J, Andreu D, Penela D, Trucco E, Cipolletta L, Arbelo E, Berne P, Tolosana JM, Pedrote A, Brugada J, Mont L, Berruezo A. Sinus rhythm detection of conducting channels and ventricular tachycardia isthmus in arrhythmogenic right ventricular cardiomyopathy. Heart Rhythm Jun 01 2014;11:747-754.
26.
Sacher F, Roberts-Thomson K, Maury P, et al. Epicardial Ventricular Tachycardia Ablation: A Multicenter Safety Study. J Am Coll Cardiol May 25, 2010 2010;55:2366-2372.
27.
Sarkozy A, Tokuda M, Tedrow UB, Sieira J, Michaud G, Couper GS, John R, Stevenson WG. Epicardial Ablation of Ventricular Tachycardia in Ischemic Heart Disease. Circ Arrhythm Electrophysiol Oct 09 2013;6:1115-1122.
28.
Andreu D, Ortiz-Perez JT, Boussy T, Fernandez-Armenta J, De Caralt TM, Perea RJ, Prat-Gonzalez S, Mont L, Brugada J, Berruezo A. Usefulness of contrast-enhanced cardiac magnetic resonance in identifying the ventricular arrhythmia substrate and the approach needed for ablation. Eur Heart J Feb 06 2014;35:1316-1326.
29.
Komatsu Y, Daly M, Sacher F, et al. Endocardial Ablation to Eliminate Epicardial Arrhythmia Substrate in Scar-Related Ventricular Tachycardia. J Am Coll Cardiol May 15 2014;63:1416-1426.
23
Clinical Perspectives To date, there is no consensus on the need and appropriate timing of epicardial ablation in post-infarction VT substrate ablation. The present study provides useful information for the selection of patients that could be candidate for first-line endoepicardial approach. Firstly, a high proportion of patients (87.5%) with transmural scar identified by means of routinely used imaging techniques had epicardial arrhythmic substrate, which indicates that infarct transmurality correctly identified patients requiring epicardial approach to completely eliminate this arrhythmogenic substrate. Secondly, the study shows that patients with transmural infarction who undergo an exclusively endocardial approach during VT substrate ablation procedures are at an increased risk of VT/VF recurrence. Therefore, according to the results of this study, infarct transmurality could be assessed and used to decide on the approach needed when the ablation procedure is aimed to completely eliminate the arrhythmic substrate. Randomized controlled trials comparing endo-epicardial vs endocardial-only approach in patients with transmural infarction would be needed to clarify the benefit of first line endo-epicardial approach for VT substrate ablation procedures.
Figure 1. Infarct transmurality criteria in an anterior myocardial infarction. A, Magnetic resonance images showing an apical left ventricular aneurysm and a transmural anterosepto-apical myocardial hyperenhancement (yellow arrow). B, Echocardiography: 4chamber view showing an aneurismatic left ventricle and apical wall thinning. C, Electroanatomic bipolar maps (left anterior oblique views) of endocardial and epicardial left ventricle surface, showing low voltage areas in segments that exhibited transmurality criteria in both ce-CMR and echocardiography. Electrograms with sequential activation pattern can be observed in endocardium and epicardium.
Figure 2. Infarct transmurality criteria in an inferoposterior myocardial infarction. A, Magnetic resonance images showing a transmural inferoposterior myocardial hyperenhancement (yellow arrows). B, Computed tomography showing basal
24
inferoposterior wall thinning. C, Electroanatomic bipolar maps (left anterior oblique views) of endocardial and epicardial left ventricle surface, showing low-voltage areas in segments that exhibited transmurality criteria in both ce-CMR and computed tomography. Electrograms with sequential activation pattern can be observed in endocardium and epicardium.
Figure 3. Study Flow Chart. MI, myocardial infarction; VT, ventricular tachycardia.
Figure 4. Kaplan-Meier curve for the endpoint of ventricular tachycardia recurrence according to infarct transmurality and type of approach. Group 1: patients with subendocardial infarction and endocardial approach. Group 2: patients with transmural infarction and endo-epicardial approach. Group 3: patients with transmural infarction and endocardial approach. VT=ventricular tachycardia.
25
Table
1.
Baseline
Clinical
Characteristics.
Group
1,
subendocardial
infarction/endocardial approach; Group 2, transmural infarction/endo-epicardial approach; Group 3. transmural infarction/endocardial approach. Group 1
Group 2
Group 3
(N=34)
(N=24)
(N=32)
Age, yrs
66.8±11.6
67.8±10.2
67.1±8.8
0.913
Follow-up, months
24.8±13.5
17.5±12.3
23.8±14.5
0.112
Hypertension
30 (88.2%)
18 (75%)
25 (78.1%)
0.289
ICD
28 (82.4%)
24 (100%)
28 (87.5%)
0.096
NYHA ≥III
6 (17.6%)
3 (12.5%)
6 (18.7%)
0.749
33.4±12
34.6±7.7
31±12
0.297
-1
15 (48.4%)
11 (45.8%)
8 (25%)
-2
6 (19.4%)
5 (20.8%)
8 (25%)
-3
6 (19.4%)
3 (12.5%)
14 (43.7%)
Class III
23 (67.6%)
12 (50%)
16 (50%)
0.252
Prior PCI
17 (50%)
13 (54.1%)
21 (65.5%)
0.745
Prior Cardiac
7 (21.2%)
0 (0%)
14 (46.8%)
0.011
LVEF, %
p value
Diseassed vessels
0.135
Surgery - CABG - CABG + valve - Valve Time from MI, yrs
6 (17.6%)
13 (40.6%)
0
1 (3.1%)
1 (2.9%)
0
16.4±7.9
18.6±9.8
14.9±10.1
- Anterior/Apical
15 (45.4%)
10 (45.8%)
11 (34.3%)
- Inferior
18 (52.9%)
12 (50%)
20 (62.5%)
- Lateral
1 (2.9%)
1 (4.2%)
1 (3.1%)
0.359
Scar localisation
0.913
26
Abbreviations: AAD, antiarrhythmic drugs; ICD, implantable cardioverter defibrillator; NYHA, New York Heart Association; LVEF, left ventricular ejection fraction; PCI, percutaneous coronary intervention; MI, myocardial infarction
27
Table 2. Substrate Mapping Data: Comparison by Procedure Type. Group 1, subendocardial infarction/endocardial approach; Group 2, transmural infarction/endoepicardial approach; Group 3, transmural infarction/endocardial approach. Group 1
Group 2
Group 3
(N=34)
(N=24)
(N=32)
521±202.9
473.5±158.4
---
478.6±257.5
---
60.4± 33.2
63.5±34.6
72.4±34.1
---
48.2±31.6
---
- endocardial
57.1±31,5
73.8±31.5
75.7±45.3
- endocardial
---
46.3±25.9
---
23.5±15.4
18.2±10.8
27.6±15.1
--
7.7±7.2
---
32 (94.1%)
20(83.3%)
25(78.1%)
p value
No of points - endocardial - epicardial
553.4±205.2 0.335 n/a
Scar area < 1.5 mV (cm2) - endocardial - epicardial
0.465 n/a
No of E-DCs 0.096 n/a
No of RF applications - endocardial - epicardial
Complete CC-EG elimination
0.065 n/a
0.170
(%)
Abbreviations: Endo-Endo, subendocardial scar with endocardial approach; TransEndo, transmural scar with endocardial approach; Trans-Endo/Epi, transmural scar with endo-epicardial approach; N values, number of procedures; CC-EG, conducting channel electrogram; E-DC, electrogram with delayed component; RF, radiofrequency.
28
Table 3. Univariate and Multivariate Cox Regression Analysis for the Association Between Clinical and Procedure-related Variables for the Study Endpoint (VT Recurrence). Univariate
P
HR (95%CI)
Multivariate
P
HR (95%CI)
Age
1.03(0.98-1.07)
0.270
LVEF
0.99(0.96-1.03)
0.664
Heart failure
1.79(0.65-4.91)
0.259
Prior Cardiac Surgery
0.93(0.34-2.58)
0.937
ICD
1.06(0.31-3.60)
0.928
Class I
1.84(0.54-6.29)
0.330
Class III
1.45(0.59-3.52)
0.412
1.73(0.61-4.18)
0.225
0.99(0.99-1.01)
0.888
VT/VF 2.81(1.18-6.66)
0.019
AAD
Arrhythmic Storm/Incessant VT Clinical VT CL End-procedure
3.05(1.27-7.35)
0.013
inducibility Endo Scar area <1,5 mV 1(0.99-1.02)
0.742
(cm2) Number of EG-DC Radiofrequency
1.01(0.99-1.02)
0.181
ablation 1(0.99-1.01)
0.166
EG-DC 0.99(0.97-1.01)
0.743
time Number
of
(remap) Type of Approach - Endo-Endo
1
- Transmural-Endo/Epi
1.85(0.43-8.00)
0.410
1.49(0.34-6.49)
0.599
- Transmural-Endo
3.89(1.38-11.00)
0.01
4.03(1.42-11.43)
0.009
30
31
32
33
34