Intramural needle ablation or repeated standard ablation in patients referred for repeat ablation of scar‐related ventricular tachycardia

When ventricular tachycardia (VT) recurs after standard RF ablation (sRFA) some patients benefit from repeat sRFA, whereas others warrant advanced methods such as intramural needle ablation (INA). Our objectives are to assess the utility of repeat sRFA and to clarify the benefit of INA when repeat sRFA fails in patients with VT due to structural heart disease.


| INTRODUCTION
3][4][5] Despite prior failed standard RF ablation (RFA) some patients benefit from a repeat standard RFA (sRFA), 6 whereas others require advanced ablation methods such as intramural needle ablation (INA) that targets intramural substrate. 7We have previously reported the feasibility and safety of INA for patients with recurrent VT refractory to standard ablation and medications. 7,8In that study, patients who were enrolled and taken to the electrophysiology (EP) laboratory but then had successful sRFA before INA were exited from the study.
The aim of this study was to assess how frequently repeat sRFA benefits patients referred after failed sRFA and to clarify the benefit of INA done during the same procedural setting when repeat sRFA fails or endocardial targets were not identified.

| METHODS
Patients with scar-related sustained monomorphic VT that recurred despite sRFA and antiarrhythmic drugs were prospectively enrolled under IRB-approved protocols at Vanderbilt University Medical Center and Brigham and Women's Hospital (ClinicalTrials.govidentifier: NCT01791543) between September 2016 and August 2020.All patients provided informed consent.Study data were collected and managed retrospectively using REDCap electronic data capture tools hosted at Vanderbilt University Medical Center. 9Exclusion criteria included: LV protruding thrombus, myocardial infarct within 2 months, unstable angina, Class IV heart failure or cardiogenic shock unless due to VT, contraindication to heparin, allergy to radiographic contrast dye, severe aortic stenosis or mitral regurgitation with a flail mitral leaflet, thrombocytopenia <50,000, and other disease processes likely to limit survival to <12 months. 7,8For this study, only patients with sustained monomorphic VT associated with structural heart disease that had recurred despite prior catheter ablation and antiarrhythmic drug therapy were included.
A total of 89 patients referred for sustained monomorphic VT were enrolled; 4 patients were excluded without having VT ablation due to: atrioventricular nodal reentry tachycardia (AVNRT), a large mobile thrombus in the right ventricle (RV) detected by intracardiac echocardiography (ICE), ventricular fibrillation before ablation, and no ablation target identified.The remaining 85 patients who had mapping and ablation for VT were included (Figure 1).

| Ablation procedure
The procedures were performed under conscious sedation or general anesthesia.Femoral venous and arterial access was obtained and electrophysiologic catheters and an intracardiac ultrasound (ICE) catheter (SoundStar; Biosense Webster or Viewflex, Abbott Medical) were placed.LV access was obtained via a retrograde aortic or transseptal atrial approach.Systemic anticoagulation with heparin achieved an activated clotting time of >300 s for LV mapping and ablation.Electroanatomical maps were created using a 3D-mapping system (CARTO 3, Biosense Webster).Substrate maps were created in sinus or paced rhythm with a 3. Target regions were sought within areas of low voltage scar area on the basis of anatomical mapping and pacing study including entrainment when possible.Whether to initially perform sRFA or proceed to INA after initial mapping was at the discretion of the investigator. 7The definition of no target for sRFA was typically that the VT circuit was not identified on the endocardium and prior endocardial substrate ablation had been performed.Often pacing no longer captured in the ablation areas, consistent with prior ablation.Patients who had no target for sRFA after initial mapping or had inducible VT after sRFA received needle ablation during the same procedural setting.
The procedure goal was the abolition of all inducible sustained monomorphic VTs.
The results of programmed stimulation after ablation were defined as: 1. Absence of any inducible sustained monomorphic VT.Acute procedure success was considered 1 or 2.

| sRFA procedure
sRFA was performed with irrigated catheters at a power of 30-50 W and contact force of 5-40 g with normal saline or half-normal saline irrigation aiming for an impedance drop of at least 10-15 Ω for typically 60-90 s. 10 RF applications at the target areas were usually repeated until unipolar pacing at 10 mA, 2 ms pulse width stimulus strength failed to capture.Additional substrate modification was performed guided by pace mapping and targeting abnormal fractionated potentials or isolated late potentials during sinus or a paced rhythm.

| INA procedure
Details of INA procedures have been described previously. 7,8In brief, the 8 French needle ablation catheter has a dome (tip) electrode and a single proximal ring electrode.A single hole in the dome allows a 27G nitinol needle electrode to be extended for up to 10 mm.The length of the needle is adjustable and was set to less than myocardial thickness as estimated from ICE, typically 6-9 mm.Unipolar electrograms and bipolar electrograms are obtained from the needle and both external electrodes.Unipolar needle and dome recordings were high-pass filtered at 0.5, 30 Hz, and low-pass filtered at 500 Hz.
Bipolar recordings were filtered at 30-500 Hz.The needle was extended at the endocardial sites felt to be closest to the deeper target substrate based on the initial mapping with a standard ablation catheter or a multi-electrode catheter.Unipolar pacing from the needle electrode was performed to assess tissue excitability at 10 mA, 2 ms pulse width stimulus strength.If no capture was found, the needle was retracted and mapping continued.Activation mapping and entrainment study were assessed with the needle catheter at only selected sites.To confirm intramyocardial position, 1 mL of (50% saline and 50% radiographic contrast) solution was injected manually.
Tissue staining was assessed with fluoroscopy. 11Normal saline was then infused at 2 mL/min and after 60 s RF current was applied in a unipolar fashion at the needle electrode in temperature control mode with a maximum temperature of 60°C and a maximum power of 50 W for up to 90-120 s.This system has been shown to be capable of the creation of intramural RF lesions to 10 mm in depth in experimental models. 12Unipolar needle pacing was performed to assess postablation capture for the evidence of lesion creation. 7,8cause the endocardial surface can be spared, additional endocardial RF lesions were placed with standard RF at the discretion of the investigator, usually if endocardial pacing was captured at the site.
After the procedure, antiarrhythmic drugs and anticoagulation management were at the discretion of the physicians.Patients were followed for 6 months.VT recurrence was defined as any sustained VT (>30 s) or requiring intervention for termination including implantable cardiac defibrillator shocks or anti-tachycardia pacing.
Primary endpoints 1.The prespecified efficacy endpoint: freedom from hospitalization for recurrent VT during the 6 months following ablation.
2. Safety endpoint: absence of all adverse events that are potentially device-related and occur within 30 days of the ablation procedure.
Additional secondary analyses included: acute outcomes of ablation, any VT recurrence, and clinical improvement in VT defined as a 70% decrease in VT frequency and absence of previously incessant VT without an increase in medications during the 6-month follow-up.
INA group: patients underwent intramural needle ablation after mapping or sRFA.

| RESULTS
The characteristics of the 85 patients who underwent mapping and ablation are shown in Table 1.They had a median age of 65 years 87% were male, and 60% had nonischemic cardiomyopathy (NICM).Before the ablation procedure, 82% had failed amiodarone therapy.The median number of failed prior ablation procedures was 2 (interquartile range [IQR], 1-3), including RF with half-normal saline irrigation in 15 (18%) patients, and epicardial ablation in 15 (18%).ICD shocks had occurred in 74% and VT storm (>3 episodes in 24 h) within the past 3 months in 38%.

| Standard RFA
After mapping sRFA was performed in 55 (65%) patients (Figure 2).but other faster, nonclinical VTs were inducible in 4 (4.7%), and postablation programmed stimulation was not performed due to concerns for aggravation of the hemodynamic status (not tested) in 6 (7%) patients, including one who required surgical repair of cardiac perforation.In these 30 patients (sRFA-only group), needle ablation was not performed.
In the sRFA-only group, the median number of ablation lesions was 41 (IQR, 22-55), and most of the papillary muscle and RV-free wall VTs were in this group (Table 2).A total of 23 of the 30 (77%) patients completed follow-up and 7 were lost during the 6-month follow-up.Freedom from hospitalization for VT was achieved in 20/23 (87%) (Figure 3A).At least one VT recurrence occurred in five patients (22%), but 78% were free of any VT (n = 18) and 4% were improved (n = 1) (Figure 3B,C).Most of the patients had a decrease in antiarrhythmic drugs following ablation, but the differences between admission and discharge, or admission and 6-month follow-up, did not reach statistical significance (Figure 5).

| Intramural needle ablation
INA was performed in 55 patients (INA group), including 25 who had clinically relevant VT that remained inducible after sRFA, and 30 who went directly to needle ablation after mapping without sRFA.In the 25/55 (45%) who had inducible clinically relevant VT after sRFA, the median number of sRFA lesions before INA was 16 (IQR, 9-37).
The INA target region was most commonly located in the septum (Table 2).The median number of needle ablations per patient was 13 Clinical improvement in VT was defined as a 70% decrease in VT frequency without an increase in medications.Details are described in the text.Abbreviations as in Figure 1.

| Safety
Of the 35 procedures in sRFA-only group, any procedure-related adverse event requiring therapy within 30 days occurred in two patients (6.6%) (Table 3).One patient developed a pericardial effusion following a steam pop at the basal lateral mitral annulus LV requiring surgical repair.Of the 55 procedures in the INA group, any procedure-related adverse event requiring therapy within 30 days occurred in nine patients (16%).Two patients developed pericardial effusion without hemodynamic compromise that was noted at the end of the procedure and treated with pericardiocentesis. 7Two patients developed a small pericardial effusion noted on echocardiographic imaging that did not require drainage.Two patients developed complete AV block from septal ablation, which was expected due to the VT location.There were five deaths that occurred between 29 days and 168 days after ablation in the needle ablation group.All occurred in patients with advanced heart disease, and none were related to the ablation procedure (Table 3). 8

| DISCUSSION
Patients with recurrent VT after standard ablation have an increased risk of mortality and are often difficult to manage. 13,148][19] In this series of patients with recurrent sustained VT who are suspected of having an intramural substrate and are referred for needle ablation therapy, 23% had no VT recurrence with repeat endocardial standard ablation.It would be useful to be able to identify these patients, before the procedure.Clinical characteristics of the patients adequately treated with sRFA were overall relatively similar to those who went on to receive intramural needle ablation, although some nonsignificant trends in history of drug failure, and underlying heart disease suggest that these patients had less severe substrate.Therefore, repeat mapping and standard ablation from the endocardium is a reasonable consideration for some patients, even when the intramural substrate is suspected.These observations are consistent with previous studies reporting VT recurrence rates of 29%-55% in patients with multiple prior ablation procedures who continue to have VT warranting referral for further ablation. 5,6

| Incremental benefit of intramural needle ablation
With the addition of INA, freedom from VT recurrences increased to 40/ 77 (52%) of patients (Central illustration 1).Our population had difficult arrhythmia substrate with the majority having nonischemic cardiomyopathies including sarcoid and genetic cardiomyopathies that often have difficult-to-control arrhythmias.Some had failed other approaches to ablation of intramural VT substrate including bipolar RFA, simultaneous unipolar RFA, trans coronary vascular ethanol ablation, and surgical ablation.1][22][23] INA offers the potential for acquiring intramural electrograms and pacing to identify intramural substrate (Figure 6). 8,24On the other hand, additional sRFA is still often needed and was used to address spared endocardial substrate in 24% of the needle ablation VT patients. 8It is known that septal VT substrate is often intramural and is associated with a high recurrence rate. 21,25In the present study, 51% (43/85) of all patients who failed sRFA or had no target for sRFA had septal VTs.

| Safety
The patients in the INA group had more adverse events than the sRFA-only group (16.4% vs. 6.7%;p = .31).Several factors contributed.They had longer procedures as needle ablation was performed after failed sRFA for 45% and they likely had more difficulty in identifying arrhythmia substrate (Table 1).Pericardial effusion requiring treatment, which might be expected to be more frequent with INA, occurred in one patient (3.3%) treated with sRFA only and two (3.6%) with INA.The numbers are insufficient for comparison, but the rates do not appear to be outside of expectations with sRFA for VT. 13,26,27AV block occurred in two INA-treated patients and was expected due to the basal septal location of the VT substrate.
5-mm tip standard ablation catheter (ThermoCool ® SmartTouch™, CF-sensing catheter, Biosense Webster) or a multi-electrode catheter (PentaRay ® NAV or Decanav Catheters, Biosense Webster).ECG and electrograms were also stored in a digital recording system (GE Medical, Inc).Bipolar recordings were filtered at 30-500 Hz.Unipolar recordings were high-pass filtered at 0.5 Hz and low-pass filtered at 500 Hz.Low voltage scar areas were defined as having a peak-to-peak bipolar F I G U R E 1 Patient flow chart.Of 89 patients enrolled４patients were excluded with no ablation.Ablation was performed in 85 patients.Patients who failed standard RFA or had no target for standard RFA had INA.AVNRT, atrial ventricular nodal reentry tachycardia; INA, intramural needle ablation; RFA, radiofrequency ablation; VF, ventricular fibrillation.electrogram amplitude <1.5 mV.Low amplitude unipolar electrograms were defined as <8.3 mV for the LV and <5.5 mV for the RVfree wall.VT was induced with programmed stimulation with up to four extra stimuli at two drive cycle lengths and burst pacing with epinephrine or isoproterenol infusion if required.

2 .
Absence of clinically relevant VT, but other faster, nonclinical VTs are inducible.3. Clinically relevant VT remains inducible.4.Not tested: postablation programmed stimulation was not performed due to concerns for aggravation of the hemodynamic status.
Following sRFA, there was absence of any inducible sustained monomorphic VT in 20/85 (23.5%), absence of clinically relevant VT, F I G U R E 2 Acute post-procedural outcomes of standard RFA.Standard RFA was performed in 55 patients and results are indicated.See text for further explanation.Abbreviations as in Figure 1.T A B L E 2 Procedural data.

(IQR, 8 -
25).Additional standard ablation was used after needle ablation in 20 patients due to evidence of endocardial surface sparing after INA in 5 patients and the persistent presence of inducible VTs in 15 patients; including 5 patients with both reasons for additional RF.In the 30 patients who went directly to needle ablation after mapping without initial sRFA, sRFA was performed after needle ablation in 13 patients due to evidence of endocardial sparing in 4 patients and the persistent presence of inducible VTs in 9 patients including 5 patients with both.At the end of the procedure, inducible VTs were abolished F I G U R E 3 Outcomes during the 6-month follow-up in the standard RFA-only group.(A) Kaplan-Meier survival curve showing VT hospitalization-free survival.(B) Kaplan-Meier survival curve showing VT recurrence-free survival.(C) Outcomes during the 6-month follow-up.

4
Outcomes in the intramural needle ablation group.(A) Acute outcomes at the end of the procedure.(B) Kaplan-Meier survival curve showing hospitalization-free survival.(C) Kaplan-Meier survival curve showing VT recurrence-free survival.(D) VT recurrence during the 6-month follow-up.Details are described in the text.Abbreviations as in Figure 1.

F I G U R E 5
Comparison of medications at admission, discharge, and 6-month follow-up.(A) Standard RFA-only group.(B) INA group.AAD, antiarrhythmic drug; FU, follow-up.Other abbreviations as in Figure 1.T A B L E 3 Complications and death.

F I G U R E 6
Intramural substrate in nonischemic cardiomyopathy (NICM).Data from a patient with NICM.(A) The bipolar voltage map shows periaorta and perimitral scar.Gray tags indicate sites where pacing failed to capture before ablation.Black tags indicate sites where pacing failed to capture after ablation.Red tags are standard RFA sites.Pink tags are INA sites.(B) At this site near the lateral mitral annulus (red arrow), endocardial pacing did not capture (not shown).A late potential (yellow arrows) is seen on the Needle-ring bipolar and Needle-dome bipolar electrograms consistent with intramural substrate and pace-mapping from the needle (panel C) captures and demonstrates a good pace match to the VT (panel D).Abbreviations as in Figure 1.
Continuous variables were presented as mean ± SD, or as medians and interquartile ranges.The Shapiro-Wilk test was used to check for the normality of data distribution.Comparisons of continuous variables were tested by the Student's t test or Wilcoxon signedrank test as appropriate.Categorical data were presented as n and percentage.Comparisons of categorical data were tested by the Fisher exact test or the chi-square test.Kaplan-Meier survival analysis was performed to estimate survival hospitalization for VT T A B L E 1 Clinical characteristics.
Incremental benefit of INA to standard RF ablation sRFA-only groups and INA groups were similar in age, sex, left ventricular ejection fraction (LVEF), and the presence of NICM (Table1).The INA group tended to have more incessant VT, prior epicardial ablation, and had failed a greater variety of antiarrhythmic drugs, suggesting a more difficult arrhythmia substrate.Considering the 77 patients with follow-up, sRFA abolished recurrent VT for 23%