Inducible Ventricular Tachycardia Research Articles

PO-03-090 NOVEL HIGH RESOLUTION MR IMAGING IMPROVES PRE-PROCEDURE IDENTIFICATION OF ABLATION TARGETS IN POST-INFARCT VENTRICULAR TACHYCARDIA

MRI-based personalized virtual heart models (VHM) are a useful tool for reconstructing scar distribution and identifying VT circuits for planning catheter ablation procedure, an effective therapy for preventing sudden cardiac death from VT in patients with myocardial infarction. However, the MRI resolution used to reconstruct VHMs may not be sufficient to accurately detect all VT circuits, possibly leading to erroneous predictions. To predict catheter ablation targets in the arrhythmogenic substrate using VHMs reconstructed from both clinical and high-resolution 2D MRI datasets and compare the predictions. High-resolution (1.352 x 3mm) short-axis cardiac MRI were acquired by combining two subsequent clinical resolution (1.352 x 6mm) short-axis MRI from nine post-infarct patients undergoing VT ablation. The high-resolution and two clinical MRI were used to reconstruct a total of three personalized VHMs for each patient that represented the patient-specific infarct remodeling. Rapid pacing was used to assess the VT circuits and identify ablation targets in each VHM. Differences in VT inducibility and location were assessed between the high and clinical resolution VHM reconstructions, as well as between the two clinical resolution VHM reconstructions. Virtual ablations were performed to identify emergent VTs and were also compared between the VHMs for each patient. The amount of fibrotic remodeling changed by 12.6 ± 3.3% between the high-resolution and two clinical MRI VHMs for each patient, while the distribution was only moderately affected (Fig 1). The heterogeneity of the myocardium and the fractal dimension (complexity) of the scar tissue was not statistically different between the VHMs for each patient (Fig 1). VT inducibility was observed in all VHMs with an average of 2.7 [1-4] unique VT morphologies induced in each VHM. In two patients, only one clinical VHM was able to identify all the unique VT morphologies observed in the high-resolution VHM. VT exit sites in the clinical MRI VHMs were within 5mm of the exit sites observed in the high-resolution VHMs in 72.2% of cases. Virtual ablations uncovered emergent VT circuits in two of the high-resolution VHMs, compared to only one of the corresponding clinical MRI VHMs. The distribution of ablation targets required to terminate VT was statistically different in 44.4% of cases (Fig 1). VHMs reconstructed from high-resolution MRI more accurately identify VT circuits and may improve catheter ablation outcomes.

PO-05-002 ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY WITH EXTENSIVE ABNORMAL SUBSTRATE: IS ISOLATION POSSIBLE?

In arrhythmogenic right ventricular cardiomyopathy (ARVC) patients with extensive right ventricular free wall (RVFW) abnormal substrate, large area homogenization with combined epicardial and endocardial approach is time consuming and often inadequate for modification. We aim to explore the feasibility and efficacy of RVFW abnormal substrate isolation in such patients to control ventricular tachycardia (VT). Eight consecutive ARVC patients with VT who had extensive abnormal RVFW substrate were included. VT induction was performed before substrate mapping and modification. Detailed voltage mapping was done during sinus rhythm. A circumferential linear lesion was deployed along the border zone of low-voltage-area on the RVFW to achieve electrical isolation. Other small areas with fractionated or late potentials were further homogenized. All eight patients had extensive RV endocardial low-voltage-area (113.8 ± 84.1 cm2, 49.6 ± 29.8%) and dense scar (59.6 ± 39.8 cm2, 25.0 ± 14.1%). Electrical isolation of abnormal substrate was achieved in 5/8 (62.5%) patients via endocardial approach alone and 3/8 (37.5%) patients via a combination of endocardial and epicardial approach. Electrical isolation was verified by slow automaticity (5/8, 62.5%) or RV non-capture (3/8, 37.5%) during high output pacing inside the encircled area. VTs were induced in 6 patients before ablation and all patients rendered non-inducible after ablation. During a median follow-up of 43 months (range 24-53), 7/8 (87. 5%) patients remained free of sustained VT. Electrical isolation of RVFW is feasible and effective in ARVC patients with extensive abnormal substrate and is associated with excellent long-term rhythm control.

PO-05-007 CORONARY VENOUS ETHANOL ABLATION OF SUBEPICARDIAL SUBSTRATE IN PATIENTS WITH VENTRICULAR TACHYCARDIA AND LEFT VENTRICULAR ASSIST DEVICE.

Patients with a left ventricular assist device (LVAD) and ventricular tachycardia (VT) often have subepicardial substrate, which may not be amenable to epicardial ablation due to sternotomy-related adhesions and the LVAD itself. As an alternative approach, coronary venous ethanol ablation (VEA) can be used to ablate VT substrates without needing pericardial access. To assess the feasibility and acute safety of VEA in patients with LVAD and VT. We retrospectively studied patients with LVAD who underwent VT ablation using VEA between 8/2015 – 11/2022 at a tertiary referral medical center. Baseline patient and procedural characteristics were obtained. Of the 10 patients included, 7 presented with VT storm, 5 had prior VT ablation, 3 had multiple prior sternotomies, all were on amiodarone, 8 were on 2 or more antiarrhythmic drugs in the prior year, all had prior defibrillator implants, and 9 had shocks in the prior year. Across the cohort, 4 different vein territories were targeted for VEA, including the middle cardiac vein, posterolateral branch vein, anterolateral branch vein, and septal branch of the anterior interventricular vein. In 4 cases, 2 separate vein territories were targeted. An average of 17 ± 10 cc of ethanol was used per case. Concomitant radiofrequency ablation was used in all 10 patients. Procedure and fluoroscopy times were 290 ± 56 minutes, and 32 ± 15 minutes, respectively. Acute procedural success, defined as no inducible VT, was achieved in 9 cases. There was 1 complication, which was transiently increased threshold on the LV pacing lead and RV failure necessitating prolonged inotropic support. All the patients survived to hospital discharge. In an inherently high-risk LVAD population with VT, VEA can be used as an alternative approach to target subepicardial substrate that would otherwise be inaccessible via standard percutaneous access of the pericardial space. Acute procedural success was high in this limited cohort. Further study with larger numbers of cases and longer follow up is warranted.

PO-04-189 CLINICAL OUTCOMES OF VENTRICULAR TACHYCARDIA ABLATION IN CARDIAC SARCOIDOSIS

Cardiac sarcoidosis (CS) is a known cause of ventricular tachycardia (VT) and sudden death. CS-related ventricular tachycardia (VT) is a rare disorder, and the underlying substrate and response to ablation are poorly understood. We aimed to assess clinical outcomes after catheter ablation for VT in CS patients. The meta-analysis was performed using a meta-package for R version 4.0/RStudio version 1.2, and Freeman Tukey double arcsine transformation with Hartung-Knapp random effect model was used. Outcomes measured included – (1) acute procedure success (defined as non-inducible for any VT); (2) freedom from recurrent VT; (3) redo VT ablation; (4) procedure-related complication; and (5) all-cause mortality. Eight studies from 2006 to 2021 incorporating a total of 273 patients with CS with drug-refractory VT underwent VT ablation (67% were men, mean age 50.3 ± 11.4 years, mean left ventricular ejection fraction 43.3 ± 15.3%). 83% had inducible VT with a mean inducible VT per patient of 2.9 ± 2.6. 14.7% of patients underwent epicardial-endocardial ablation, while the rest underwent endocardial-only ablation. Overall, acute procedural success was 73.7% (95% CI 45-95.1), with a procedure-related complication rate of 4.7% (95% CI 2.6-7.2). During the follow-up period (3.3±3.4 years), the pooled incidence of freedom from recurrent VT was 46.4% (95% CI 26.9–66.5), while 27.1% (95% CI 16.9-38.5) underwent redo VT ablation. All-cause mortality was 8.1% (95% CI 3.3-14.2). Catheter ablation of VT in conjunction with antiarrhythmic drugs in CS patients is safe and effective in eliminating VT or reducing the VT burden; however, recurrences are common, probably due to the inflammatory disease phase.

PO-05-070 ENDOCARDIAL RADIOFREQUENCY ABLATION OF VT STORM IN CARDIOGENIC SHOCK PATIENTS WITH MECHANICAL CIRCULATORY SUPPORT

Ventricular tachycardia (VT) storm in the setting of cardiogenic shock requiring mechanical support (MCS) carries a high mortality rate. Limited data exist in the literature using VT ablation as a treatment strategy in this cohort of patients. We aim to evaluate the outcome of patients receiving ablation in VT storm complicated by cardiogenic shock requiring MCS, as well as assess predictors for poor outcomes. This is a single-center, retrospective cohort study in patients with refractory VT and cardiogenic shock on MCS, undergoing endocardial ablation from 2015 to 2022. Complete substrate isolation with high output pacing within the scar, followed by stimulation protocols, was used to confirm substrate isolation and the success of ablation. Patients’ demographic and outcome data was obtained from chart review. The PAINESD score, a scoring system to predict early post-procedural mortality of VT ablation, was calculated for each patient. Peak lactate levels recorded during the procedure and preoperative invasive hemodynamic measurements were also taken into consideration. A total of 37 patients with VT storm and concomitant cardiogenic shock on MCS were included. The average age was 61.7 years old, 94.7% were men, with a mean left ventricular ejection fraction of 17.3%, and the average PAINESD score was 24.9. The type of mechanical support utilized is listed in Table 1. Twenty-one were discharged alive, 8 patients (21.6%) with long-term LVAD support, and 13 (35.1%) after weaning support, while 16 patients (43.2%) didn’t survive the index hospitalization (Figure 1). The PAINESD score between those who survived and those who died was not significantly different (25.3 vs. 24.3, p = 0.31). The survivor group had a significantly higher procedure success rate (76.2% vs. 35.3%, p=0.018), higher mean pulmonary artery pulsatility index (PAPI) (2.7 vs. 1.4, p = 0.005), and lower mean intraoperative peak lactic acid level (1.1 vs. 3.5 mmol/L, p = 0.027). Ablation for medication refractory ventricular arrhythmia in cardiogenic shock is efficacious in facilitating mechanical support weaning in a large proportion of the cohort. The absence of right ventricular dysfunction as measured by PAPI, intraoperative lactic acid level, and acute procedure success, as measured by VT inducibility at the end of the procedure, predict the short-term outcome, while the PAINESD score demonstrated weak differentiating power in this moribund, high-risk cohort.

AB-452673-2 REPEAT STANDARD ABLATION OR INTRAMURAL NEEDLE ABLATION AFTER FAILED STANDARD ABLATION FOR VENTRICULAR TACHYCARDIA

Some patients with recurrent scar-related VT after failed standard RF ablation (sRFA) benefit from a repeat sRFA, whereas others require advanced ablation methods such as intramural needle ablation (INA). To assess the frequency and possible clinical markers of successful repeat sRFA ablation compared to INA in patients with prior failed sRFA who were referred for INA. In consecutive pts with scar-related VT that recurred despite sRFA who were enrolled in a trial for INA, repeat sRFA was considered first. INA was performed if VT remained inducible or no sRFA targets were identified. Findings and outcomes were compared for pts treated with repeat sRFA only versus INA. We defined improvement during follow-up as a 70% decrease of VT frequency. Of 85 pts enrolled sRFA only was performed in 30 (35%) and INA was performed in 55 (65%). INA and sRFA groups were similar in heart diseases, number of prior sRFA, and VT frequency. Inducible VT was abolished or modified (acute success) in 23/85 pts (27%) with sRFA and acute success increased to 56 pts (66%) with the addition of INA when sRFA failed or targets were absent. In multivariable analysis, INA was more likely to be performed for septal VTs (Odds ratio: 5.4, 95% confidence interval: 1.9-16.6, P=0.002). Complications were similar in both groups. During follow-up improvement or abolition of VT occurred with only sRFA in 16/77 (21%) patients and increased to 42/77 (55%) with the addition of INA. In difficult to treat recurrent sustained VT that has failed standard RFA and are referred for advanced therapy, 20% have a favorable outcome with repeat standard RFA. Addition of Intramural Needle Ablation achieves a favorable outcome to over half of all patients. Septal VTs are most likely to require INA.

PO-05-037 EFFICACY AND CLINICAL CHARACTERISTICS OF AVERT-VT: ABLATION AT VIRTUAL-HEART PREDICTED VT

We have previously demonstrated the feasibility of virtual-heart simulations in determining noninvasively the optimal infarct-related ventricular tachycardia (VT) ablation targets and guiding the clinical ablation. We are now proceeding with AVERT-VT, an FDA-approved study for ten prospective patients. To develop the end-to-end personalized computational modeling prediction pipeline enabling AVERT-VT and to assess the corresponding clinical characteristics of the predicted virtual-heart ablation targets. We developed a comprehensive end-to-end computational pipeline enabling AVERT-VT (Fig). 3D LGE-MRI scans with 1.5x1.5mm in-plane spatial resolution and slice thickness <2mm were used to reconstruct the 3D left ventricular (LV) model incorporating deep scar, border (gray) zone, and non-infarcted tissue. In silico rapid pacing from 7 LV regions were performed to induce VTs. The optimal ablation targets were determined by thorough analyses of the wavefront propagation of the induced in silico VTs. A linear ablation connecting a VT ablation target to a transmural deep scar region, the basal region, or the other VT target was performed to eliminate the potential VT pathway formed by the target ablation. Potential emergent VTs in the post-ablation substrate were investigated by repeating the VT induction pacing protocol. This process was iterated until complete VT non-inducibility was achieved. The initial and repeat ablation targets, linear ablations, as well as the LV, right ventricle, infarct area, aortic arch, and left and right coronary cusp geometries, were exported as an ablation strategy plan compatible with the clinical mapping system. The figure presents results from one patient in the clinical study. The ablation plan was successfully imported and co-registered to the patient’s heart. The extent of the model infarct corresponded to the bipolar low-voltage regions. Abnormal electrograms were observed at the proposed targets. 2 VTs were observed during the procedure. Areas of latest activation in sinus rhythm and best pace maps, with a long stimulus to QRS, were found at 2 of the proposed targets. One of the seven proposed targets was not ablated due to the proximity to the left sided His potential. The patient was not inducible of any VT at the end of the procedure. AVERT-VT proposed targets corresponded to abnormal electrograms, and ablating at the targets led to VT non-inducibility.

PO-05-039 PERIPROCEDURAL ACUTE HEMODYNAMIC DECOMPENSATION ASSOCIATED WITH SUBSTRATE-BASED ABLATION OF VENTRICULAR TACHYCARDIA IN PATIENTS WITH STRUCTURAL HEART DISEASE – RARE AND NONPREDICTABLE EVENT

Patients with structural heart disease (SHD) and recurrent ventricular tachycardia (VT) are at considerable risk of periprocedural complications of radiofrequency (RF) catheter ablation including acute hemodynamic decompensation (AHD). The PAINESD score [sum of 5, 3, 6, 6, 3, 5, and 3 points for chronic obstructive pulmonary disease (COPD), age >60 years, ischemic cardiomyopathy (ICM), NYHA Class >2, LV ejection fraction (LVEF) <25%, electrical storm (ES), and diabetes mellitus (DM), respectively] was proposed to predict the risk of AHD, and identify the patients who may benefit from pre-emptive use of percutaneous left ventricular assist device (pVAD). The single-center, retrospective study investigated the incidence of AHD in large-volume, tertiary referral EP center and the predictive power of the PAINESD score. We included patients who had their first ablation for SHD-related VT between August 2006 and December 2020. The procedure was performed under conscious sedation except for patients who were on mechanical ventilation because of hemodynamical or electrical instability before the ablation. Substrate mapping/ablation was performed primarily during spontaneous rhythm or right-ventricular pacing. Activation and entrainment mapping were used rarely, only in well-tolerated VTs. The goal of ablation was to abolish all inducible VTs. AHD triggered by ablation procedure was defined as intra- or early post-procedural (<12 h) development of acute pulmonary oedema or refractory hypotension, requiring urgent intervention like inotropic agents and/or artificial ventilation and/or pVAD implant. The study cohort consisted of 1143 patients (age: 63±13 years, males: 87%, ICM: 67%, ES: 25%, NYHA Class: 2.1±1.0, LVEF: 34±13%, DM: 32%, COPD: 12%). Their PAINESD score was 11.4 ± 6.6 (median: 12, interquartile range: 6–17). The ablation procedure (total duration 187±78 min, RF time: 23±15 min) was complicated by AHD in 13/1143 = 1.1% patients and these adverse events were not predicted by PAINESD score (Figure). We observed a substantially lower rate (1.1%) of AHD than previously reported (up to 11%). These events did not accumulate in patients with upper-tercile PAINESD score in whom the highest AHD risk was reported (up to 24%). This observation may be explained by careful substrate-based ablation under conscious sedation that prevents prolonged low-output state related to repeated VT induction and mapping in general anesthesia.

PO-05-068 MAJOR VASCULAR COMPLICATIONS IN A LARGE COHORT OF PATIENTS UNDERGOING CATHETER ABLATION FOR VPB/VT IN A HIGH-VOLUME, TERTIARY EP CENTER

Catheter ablation is an established treatment method both in patients with idiopathic premature ventricular complexes (PVC) or ventricular tachycardia (VT) and in structural heart disease (SHD) VT. Major vascular complications (MVCs) are the most frequent in these populations. A retrospective study investigating the incidence of MVCs in large-volume, specialized VT center and analyzing their predictors. We included PVC/VT patients who had their first ablation procedure between August 2006 - December 2020. The procedures were performed under conscious sedation except for patients who were on mechanical ventilation because of hemodynamical or electrical instabilit. Activation mapping supported by an electroanatomic mapping system was used in idiopathic cases. In SHD, substrate mapping using an electroanatomic mapping system and pacemapping was employed as a prerequisite for complete substrate modification during spontaneous rhythm or pacing. Activation and entrainment mapping for well-tolerated VTs were rarely used. The goal of ablation was to abolish all inducible VTs. A specific institutional tracking system for complications of invasive procedures was used to collect all periprocedural complications that were subsequently adjudicated. MVCs were defined as those that result in permanent injury or death, require intervention or treatment, prolong hospitalization (>48 hrs) or require new hospitalization. Idiopathic PVC/VT ablation was performed in 656 pts (males: 50%, age: 51 ± 17 years, re-ablations: 15%). SHD VT was ablated in 1637 pts (males: 88%, age: 63 ± 13 years, re-ablations: 30%, ischemic cardiomyopathy: 65%, left ventricular ejection fraction: 34 ± 13%, electrical storm: 24%). In idiopathic PVC/VT, MVCs were observed in 2.4 % (4.0% in males vs. 0.9% in females, P <0.01). In SHD, the rate of MVCs reached 3.5 % (2.8% in males vs. 9.4% in females, P <0.00001). Based on the multivariable regression model, the composite risk score to predict MVCs was proposed that was calculated as a sum of risk points for age (0, 1, 2, and 3 points for <50, 50–59, 60–69, and ≥70 years, respectively), female gender (2 points), and serum creatinine >1.3mg/dL (2 points), range 0–7 (Figure). While in an idiopathic setting, MVCs were more frequent in males, which may reflect a higher proportion of more complex LV ablations and arterial access, there was a significant female predominance in MVCs in SHD. The composite risk score predicts the risk of MVCs independently of VT cause.

CE-452773-4 ANATOMY OF THE ISTHMUS: UNRAVELING TISSUE COMPOSITION OF VENTRICULAR TACHYCARDIA DIASTOLIC PATHWAY

Unequal tissue composition of post-myocardial infarction (MI) scar (viable myocardium, fibrosis, fatty infiltration) leads to heterogeneous conduction properties and excitability. The presence of a protected diastolic, slow-conducting pathway (isthmus) is the electrophysiological landmark of post-MI reentrant ventricular tachycardia (VT). Contemporary histological studies evaluating the tissue features needed for slow, protected conduction during VT are lacking. To characterize tissue composition singularities of confirmed VT isthmuses (VTI) in a chronic MI swine model, and to compare it to non-isthmus scar (NIS). One-month after a non-reperfused anterior MI, 9 Landrace X Large White pigs (4 female; 33.6±2.2 Kg) with inducible VT underwent high-density activation mapping to define the diastolic corridor. VTI was defined as part of the diastolic pathway exhibiting mid-diastolic potentials. Discrete radiofrequency applications were delivered in the vicinity of the VTI and used as tissue landmarks to guide the ex vivo isthmus localization. Tissue transverse samples (5 mm) from the labelled VTI and NIS were obtained for further histological and immunohistochemical analysis. Dense scar and border zones were analyzed. Compared to NIS, border zone of VTI showed significantly higher fatty infiltration (p=0.016) and dense scar displayed less Collagen I (p=0.053), Collagen III (p=0.043), and Collagen Volume Fraction (p=0.027), without differences in the overall fibrotic deposition (P=0.119). Immunohistochemical studies revealed greater vascular density (Isolectin B4-positive vessels) at VTI, compared to NIS (p=0.018). Arteries and veins at the VTI were mostly surrounded by preserved cardiomyocytes (figure). Viable cardiomyocytes and fibroblasts at VTI displayed higher density of Cx43 and Cx40, respectively, compared to those at NIS (p=0.022 and p=0.004, respectively), despite no differences in cTnI, SERCA2 and Vimentin expression. The VTI exhibits distinctive tissue features compared to NIS. Unique electrophysiological properties of the VTI may be driven by increased adipocytic deposition, vascular density and Cx43/Cx40 expression, as well as lower presence of Collagen III and Collagen Volume Fraction.

PO-05-034 CLINICAL CHARACTERISTICS AND OUTCOMES AFTER VENTRICULAR TACHYCARDIA ABLATION USING ULTRALOW TEMPERATURE CRYOABLATION IN PATIENTS WITH PRIOR CATHETER ABLATION

Ablation of scar mediated Ventricular Tachycardia (VT), especially when the location of circuit is intramural can be quite challenging with the use of radiofrequency (RF) ablation. Preclinical data with the use of Ultralow temperature Cryoablation has shown that it can create deep, transmural lesions and can generate temperature as low as -196° C. To present a series of patients who had recurrent VT despite prior RF ablation and then underwent VT ablation with Ultralow temperature cryoablation system (Adagio) as part of the FDA compassionate use authorization. We performed retrospective analysis of patients who had undergone VT ablation using the Adagio system. Follow up data on clinical outcomes and recurrence of VT episodes were collected based on clinic visits, device interrogations and remote transmissions from Implantable Cardioverter Defibrillators (ICDs). A total of 5 patients underwent Ultralow temperature cryoablation for VT between 10/2021 and 05/2022 at our institution. The average age of patients in our case-series was 72 +/- 8.6 years and 3 (60%) of patients had h/o ischemic cardiomyopathy. The median number of prior VT ablations performed per patient was 2, and 40% of patients had presented in electric storm. During the VT ablation procedure using the Adagio system, the average number of inducible VT episodes was 2.6 +/- 1.8. All 5 patients were non-inducible at the end of VT ablation. At an average follow up period of 207.6 +/- 77.7 days, after having undergone VT ablation using the Adagio system, all 5 patients remained free of ICD shocks or electric storm during the follow up period and only 2 patients were maintained on anti-arrhythmic therapy. One patient underwent cardiac transplant because of recurrence of relatively slow VT episodes and advanced congestive heart failure. It is also worthwhile to note that in this patient, given the inaccessible location of VT circuit (peri-mitral region after prior cardiac surgery for cardiac aneurysm), ablation lesions could not be optimally delivered. Another patient experienced 1 episode of slow monomorphic VT, which was ATP terminable. Although our experience is based on a small sample size, the follow up outcomes using Ultralow temperature Cryoablation system for VT ablation in a challenging patient subset with limited options seems promising. Future studies would yield data on efficacy and safety of this system in high-risk subset of patients.

PO-05-089 COMPARISON OF VIRTUAL HEART ARRHYTHMIA ABLATION TARGETING PREDICTIONS WITH AREAS OF ISOCHRONAL CROWDING IN SCAR-DEPENDENT VENTRICULAR TACHYCARDIA

Isochronal late activation mapping (ILAM) is a functional substrate mapping technique which detects deceleration zones (DZ) in those with scar-dependent VT. DZ have been shown to correlate with the critical isthmus during re-entrant VT. Personalised virtual heart arrhythmia ablation targeting (VAAT) is a technique which aims to non-invasively identify the optimum ablation targets through computational modelling. The association of the VAAT predictions with DZ is unknown, nor is the effect of extrastimulus pacing on identification of DZ. To assess to relationship between VAAT predicted targets with areas of slow conduction on ILAM in those with scar-dependent VT. Gadolinium-enhanced MRI scans were used to reconstruct virtual heart models. Simulated ventricular pacing was performed to demonstrate VT inducibility and predict optimum lesion sets to terminate all likely VTs in the models. ILAMs were generated by annotating the latest activation of ventricular electrograms during right ventricular and extrastimulus pacing at 20ms above VERP. DZ were defined as > 3 isochrones in a 1cm radius. VAAT predictions were superimposed on the invasive ILAM. The spatial relationship was assessed. DZ identified during RV and extrastimulus pacing were compared. 11 patients (100% male) with scar-dependent VT underwent invasive ILAM mapping and VAAT protocol. 3195 ± 935 EAM points per patient were analysed. Mean VAAT-predicted area was 11.2 ± 4.3 cm2 representing 22.3% of the total MRI infarct area. RV pacing identified 13 DZ (mean 1.2 DZ per patient, range 0-3). 10/13 (76.9%) were located within 5mm of a VAAT predicted site, whereas 3/13 (23.1%) were remote (>5mm from a predicted site). Extrastimulus pacing identified 25 DZ (mean 2.3 DZ per patient, range 1-4). 21/25 (84%) were within 5mm of a VAAT predicted site, 4/25 (16%) were remote. More DZ were identified during extrastimulus compared to RV pacing (25 vs 13, p = 0.04). The mean distance of RV pacing-identified DZ and extrastimulus-identified DZ from VAAT predictions was not significantly different (3.3 ± 6.7 mm vs 2.9 ± 5.4 mm respectively, p = 0.84). 11/13 (84.6%) of RV pacing-identified DZ were also identified by extrastimulus pacing. 14/25 (56%) of extrastimulus-identified DZ were novel, having not been detected by RV pacing. Deceleration zones visualised on ILAM are closely spatially associated with VAAT-predicted optimum targets for VT ablation. Extrastimulus pacing identifies significantly more DZ compared to RV pacing.

Radiofrequency catheter ablation of ventricular tachycardia using combined endocardial techniques in patients with structural heart disease improves procedural effectiveness and reduces arrhythmia episodes.

Evidence indicates that radiofrequency catheter ablation (RFCA) of ventricular tachycardia (VT) in patients with structural heart disease (SHD) is safe and effective. However, arrhythmia recurrence is still relatively high, and the optimal procedural strategy is unclear. In clinical practice, several combinations of mapping and ablation techniques are used to improve VT ablation efficacy. The study aimed to evaluate and provide evidence on the efficiency and safety of a systematized combination of VT ablation (mapping) techniques in patients with SHD. From 2016 to 2019, 47 patients (54 procedures) with SHD (89% heart failure, 94% ischemic heart disease, 37% VT storm) who underwent RFCA of VT were retrospectively analyzed from a group of 58 consecutive patients. During RFCA of VT, different combinations of three techniques, activation mapping (AM), pace mapping (PM), and substrate-based mapping (SbM), were used. The procedures were performed using the CARTO® 3 (Biosense Webster Inc., Diamond Bar, CA, US) electro-anatomical mapping system. During a median (interquartile range [IQR]) follow-up of 25.5 months (11.75-52.25), VT-free survival after ablation was 68.5% (n = 37/54 procedures). Acute procedural success was achieved in 85% (n = 46/54 procedures). The number of induced VT morphologies, induction of non-clinical or non-sustained VT after ablation, and fewer VT mapping techniques used during the procedure were related to decreasing VT-free survival. VT ablation strategy based on systemic use of combined techniques is effective and safe in long-term follow-up of patients with SHD.

Evaluation of a deep learning-enabled automated computational heart modelling workflow for personalized assessment of ventricular arrhythmias.

Personalized, image-based computational heart modelling is a powerful technology that can be used to improve patient-specific arrhythmia risk stratification and ventricular tachycardia (VT) ablation targeting. However, most state-of-the-art methods still require manual interactions by expert users. The goal of this study is to evaluate the feasibility of an automated, deep learning-based workflow for reconstructing personalized computational electrophysiological heart models to guide patient-specific treatment of VT. Contrast-enhanced computed tomography (CE-CT) images with expert ventricular myocardium segmentations were acquired from 111 patients across five cohorts from three different institutions. A deep convolutional neural network (CNN) for segmenting left ventricular myocardium from CE-CT was developed, trained and evaluated. From both CNN-based and expert segmentations in a subset of patients, personalized electrophysiological heart models were reconstructed and rapid pacing was used to induce VTs. CNN-based and expert segmentations were more concordant in the middle myocardium than in the heart's base or apex. Wavefront propagation during pacing was similar between CNN-based and original heart models. Between most sets of heart models, VT inducibility was the same, the number of induced VTs was strongly correlated, and VT circuits co-localized. Our results demonstrate that personalized computational heart models reconstructed from deep learning-based segmentations even with a small training set size can predict similar VT inducibility and circuit locations as those from expertly-derived heart models. Hence, a user-independent, automated framework for simulating arrhythmias in personalized heart models could feasibly be used in clinical settings to aid VT risk stratification and guide VT ablation therapy. KEY POINTS: Personalized electrophysiological heart modelling can aid in patient-specific ventricular tachycardia (VT) risk stratification and VT ablation targeting. Current state-of-the-art, image-based heart models for VT prediction require expert-dependent, manual interactions that may not be accessible across clinical settings. In this study, we develop an automated, deep learning-based workflow for reconstructing personalized heart models capable of simulating arrhythmias and compare its predictions with that of expert-generated heart models. The number and location of VTs was similar between heart models generated from the deep learning-based workflow and expert-generated heart models. These results demonstrate the feasibility of using an automated computational heart modelling workflow to aid in VT therapeutics and has implications for generalizing personalized computational heart technology to a broad range of clinical centres.

Experimental venous thrombus resolution is driven by IL-6 mediated monocyte actions

Deep venous thrombosis and residual thrombus burden correlates with circulating IL-6 levels in humans. To investigate the cellular source and role of IL-6 in thrombus resolution, Wild type C57BL/6J (WT), and IL-6−/− mice underwent induction of VT via inferior vena cava (IVC) stenosis or stasis. Vein wall (VW) and thrombus were analyzed by western blot, immunohistochemistry, and flow cytometry. Adoptive transfer of WT bone marrow derived monocytes was performed into IL6-/- mice to assess for rescue. Cultured BMDMs from WT and IL-6−/− mice underwent quantitative real time PCR and immunoblotting for fibrinolytic factors and matrix metalloproteinase activity. No differences in baseline coagulation function or platelet function were found between WT and IL-6−/− mice. VW and thrombus IL-6 and IL-6 leukocyte-specific receptor CD126 were elevated in a time-dependent fashion in both VT models. Ly6Clo Mo/MØ were the predominant leukocyte source of IL-6. IL-6−/− mice demonstrated larger, non-resolving stasis thrombi with less neovascularization, despite a similar number of monocytes/macrophages (Mo/MØ). Adoptive transfer of WT BMDM into IL-6−/− mice undergoing stasis VT resulted in phenotype rescue. Human specimens of endophlebectomized tissue showed co-staining of Monocyte and IL-6 receptor. Thrombosis matrix analysis revealed significantly increased thrombus fibronectin and collagen in IL-6−/− mice. MMP9 activity in vitro depended on endogenous IL-6 expression in Mo/MØ, and IL-6−/− mice exhibited stunted matrix metalloproteinase activity. Lack of IL-6 signaling impairs thrombus resolution potentially via dysregulation of MMP-9 leading to impaired thrombus recanalization and resolution. Restoring or augmenting monocyte-mediated IL-6 signaling in IL-6 deficient or normal subjects, respectively, may represent a non-anticoagulant target to improve thrombus resolution.

Ventricular anatomical complexity and sex differences impact predictions from electrophysiological computational models.

The aim of this work was to analyze the influence of sex hormones and anatomical details (trabeculations and false tendons) on the electrophysiology of healthy human hearts. Additionally, sex- and anatomy-dependent effects of ventricular tachycardia (VT) inducibility are presented. To this end, four anatomically normal, human, biventricular geometries (two male, two female), with identifiable trabeculations, were obtained from high-resolution, ex-vivo MRI and represented by detailed and smoothed geometrical models (with and without the trabeculations). Additionally one model was augmented by a scar. The electrophysiology finite element model (FEM) simulations were carried out, using O'Hara-Rudy human myocyte model with sex phenotypes of Yang and Clancy. A systematic comparison between detailed vs smooth anatomies, male vs female normal hearts was carried out. The heart with a myocardial infarction was subjected to a programmed stimulus protocol to identify the effects of sex and anatomical detail on ventricular tachycardia inducibility. All female hearts presented QT-interval prolongation however the prolongation interval in comparison to the male phenotypes was anatomy-dependent and was not correlated to the size of the heart. Detailed geometries showed QRS fractionation and increased T-wave magnitude in comparison to the corresponding smoothed geometries. A variety of sustained VTs were obtained in the detailed and smoothed male geometries at different pacing locations, which provide evidence of the geometry-dependent differences regarding the prediction of the locations of reentry channels. In the female phenotype, sustained VTs were induced in both detailed and smooth geometries with RV apex pacing, however no consistent reentry channels were identified. Anatomical and physiological cardiac features play an important role defining risk in cardiac disease. These are often excluded from cardiac electrophysiology simulations. The assumption that the cardiac endocardium is smooth may produce inaccurate predictions towards the location of reentry channels in in-silico tachycardia inducibility studies.

Biophysical Tissue Characterization of Ventricular Tachycardia Substrate With Local Impedance Mapping to Predict Critical Sites

BackgroundNew tools are needed to improve ventricular tachycardia (VT) substrate characterization and optimize outcomes. LI provides biophysical tissue characterization. ObjectivesThe purpose of this study was to test local impedance (LI)-based mapping to predict critical ventricular tachycardia components after myocardial infarction (MI). MethodsOne month after a nonreperfused anterior MI, endo-epicardial high-density electroanatomic mapping and endocardial LI mapping were performed in 23 Landrace Large X White pigs. LI thresholds were set using the blood pool value to define a 10 Ω range: low (<blood pool −1Ω), intermediate (≥blood pool −1Ω and ≤blood pool +9Ω), and high (normal) tissue resistance (>blood pool +9Ω). ResultsLow LI was detected in low-voltage areas in 100% of cases, but intermediate LI was found in both core (87%) and border zone (12.5%) voltage areas. A total of 17 VTs were induced (VT isthmus identified in 9 animals). VT inducibility was associated with the size of intermediate LI area (OR: 1.19 [95% CI: 1.0-1.4]; P = 0.039) and the presence of specific LI patterns: LI corridor (OR: 15.0 [95% CI: 1.3-169.9]; P = 0.029); LI gradient (OR: 30.0 [95% CI: 2.1-421.1]; P = 0.012), high LI heterogeneity (OR: 21.7 [95% CI: 1.8-260.6]; P = 0.015), and presence of ≥2 low LI regions (OR: 11.3 [95% CI: 1.0-130.2]; P = 0.053). Potential VT isthmuses were in areas of intermediate LI and colocalized to LI patterns associated with VT inducibility in all cases (LI corridors or LI gradient). Low LI regions did not actively participate in the VT circuit (0%). ConclusionsLI mapping is feasible and may add useful characterization of the VT substrate. Specific LI patterns (ie, corridors, gradients) were associated with VT inducibility and colocalized with the VT isthmus, thus representing a potential new target for ablation in substrate-based procedures.

Matching Ablation Endpoints to Long-Term Outcome: The Prospective Multicenter Italian Ventricular Tachycardia Ablation Registry

BackgroundMulticenter ventricular tachycardia (VT) ablation studies have shown poorer outcomes compared with single-center experiences. This difference could be related to heterogeneous mapping and ablation strategies. ObjectivesThis study evaluated a homogenous simplified catheter ablation strategy for different substrates and compared the results with those of a single referral center. MethodsThis was a multicenter prospective VT ablation registry of patients with the following 4 causes of VT: previous myocardial infarction; previous myocarditis; arrhythmogenic right ventricular dysplasia; or idiopathic dilated cardiomyopathy. The procedural protocol included precise mapping and ablation steps with the combined endpoint of late potential (LP) abolition and noninducibility of VT. The long-term primary efficacy endpoint was freedom from VT. ResultsA total of 309 patients were enrolled. LPs were present in 70% of patients and were abolished in 83%. At the end of the procedure 74% of LPs were noninducible. The primary combined endpoint of LP abolition and noninducibility was achieved in 64% of patients with LPs at baseline. Freedom from VT at 12 months was observed in 67% of patients. In the overall study group, VT inducibility was the only predictor of freedom from VT (P = 0.013). In patients with LPs, the VT recurrence rate was lower both for patients with complete LP abolition (P = 0.040) and for patients meeting the composite endpoint (P = 0.035). ConclusionsA standardized VT mapping and ablation technique reproduced the procedural outcomes of a single referral center in a multicenter prospective study. LP abolition and noninducibility were effective in reducing VT recurrences in patients with 4 causes of cardiomyopathy. (Ventricular Tachycardia Ablation Registry; NCT03649022)

Assessing the arrhythmogenic risk of engineered heart tissue patches through in silico application on infarcted ventricle models

BackgroundPost myocardial infarction (MI) ventricles contain fibrotic tissue and may have disrupted electrical properties, both of which predispose to an increased risk of life-threatening arrhythmias. Application of epicardial patches obtained from human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are a potential long-term therapy to treat heart failure resulting from post MI remodelling. However, whether the introduction of these patches is anti- or pro-arrhythmic has not been studied. MethodsWe studied arrhythmic risk using in silico engineered heart tissue (EHT) patch engraftment on human post-MI ventricular models. Two patient models were studied, including one with a large dense scar and one with an apparent channel of preserved viability bordered on both sides by scar. In each heart model a virtual EHT patch was introduced as a layer of viable tissue overlying the scarred area, with hiPSC-CMs electrophysiological properties. The incidence of re-entrant and sustained activation in simulations with and without EHT patches was assessed and the arrhythmia inducibility compared in the context of different EHT patch properties (conduction velocity (CV) and action potential duration (APD)). The impact of the EHT patch on the likelihood of focal ectopic impulse propagation was estimated by assessing the minimum stimulus strength and duration required to generate a propagating impulse in the scar border zone (BZ) with and without patch. ResultsWe uncovered two main mechanisms by which ventricular tachycardia (VT) risk could be either augmented or attenuated by the interaction of the patch with the tissue. In the case of isthmus-related VT, our simulations predict that EHT patches can prevent the induction of VT when the, generally longer, hiPSC-CMs APD is reduced towards more physiological values. In the case of large dense scar, we found that, an EHT patch with CV similar to the host myocardium does not promote VT, while EHT patches with lower CV increase the risk of VT, by promoting both non-sustained and sustained re-entry. Finally, our simulations indicate that electrically coupled EHT patches reduce the likelihood of propagation of focal ectopic impulses. ConclusionsThe introduction of EHT patches as a treatment for heart failure has the potential to augment or attenuate the risk of ventricular arrhythmias, and variations in the anatomic configuration of the substrate, the functional properties of the BZ and the electrophysiologic properties of the patch itself will determine the overall impact. Planning for delivery of this therapy will need to consider the possible impact on arrhythmia.

Correlations Between Endocardial Voltage Mapping, Diagnosis, and Genetics in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

The relations between endocardial voltage mapping and the genetic background of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) have not been investigated so far. A total of 97 patients with proved or suspected ARVC who underwent 3-dimensional endocardial mapping and genetic testing have been retrospectively included. Presence, localization, and size of scar areas were correlated to ARVC diagnosis and the presence of a pathogenic variant. A total of 78 patients (80%) presented with some bipolar or unipolar scar on endocardial voltage mapping, whereas 43 carried pathogenic variants (44%). Significant associations were observed between presence of endocardial scars on voltage mapping and previous or inducible ventricular tachycardia, right ventricular function and dimensions, or electrocardiogram features of ARVC. A total of 60 of the 78 patients (77%) with an endocardial scar fulfilled the criteria for a definitive arrhythmogenic right ventricular dysplasia diagnosis versus 8 of 19 patients (42%) without scar (p=0.003). Patients with a definitive diagnosis of ARVC had more scars from any location and the scars were larger in patients with ARVC. In the 68 patients with a definitive diagnosis of ARVC, the presence of any endocardial scar was similar whether an ARVC-causal mutation was present or not. Only scar extent was significantly greater in patients with pathogenic variants. There was no difference in the presence and characteristics of scars in PKP2 mutated versus other mutated patients. The 3-dimensional endocardial mapping could have an important role for refining ARVC diagnosis and may be able to detect minor forms with otherwise insufficient criteria for diagnosis. The trend for larger scar extent were observed in mutated patients, without any difference according to the mutated genes.