Ventricular Tachycardia Circuit Research Articles

Analysis of electrogram peak frequency during ventricular tachycardia ablation: Insights into human tridimensional ventricular tachycardia circuits

Analysis of electrogram peak frequency during ventricular tachycardia ablation: Insights into human tridimensional ventricular tachycardia circuits

Tissue composition underlying local impedance in chronic infarction: an histological study

Abstract Background Local impedance (LI) mapping is feasible and provides additional tissue characterization of the ventricular tachycardia (VT) substrate. VT isthmuses are usually located in areas of intermediate LI while low LI regions did not actively participate in the VT circuit. Histological studies evaluating the tissue composition underlying different LI values are lacking. Purpose To describe the tissue composition underling different LI subtypes in a chronic myocardial infarction (MI) swine model. Methods One-month after a non-reperfused anterior MI, five Landrace X Large White pigs underwent endocardial LI mapping (figure 1). LI thresholds were set using the blood-pool LI value to define low, intermediate, and high tissue resistance subtypes. A navigated needle-catheter was used to inject methylene-blue at sites with intermediate and low LI to guide the ex vivo tissue localization. Tissue was obtained for further histological analysis. Low and intermediate LI zones were analysed. Results A total of six and eight samples were analysed for low and intermediate LI, respectively. Compared to low LI zones, intermediate LI tissue displayed less Collagen I (1.03±0.26 vs. 0.34±0.35%, p=0.0082), Collagen III (9.92±2.98 vs. 6.47±1.80%, p=0.0380) and Collagen Volume Fraction (10.92±2.77 vs. 6.81±1.92, p=0.0163), without differences in the overall fibrotic and adipocytic deposition (figure 2). No significant differences in the Cx43, CTnI and SERCA2 expression were observed. Conclusion LI subtypes showed distinctive histological composition. Intermediate LI sites displayed less collagen content (I, III and collagen volume fraction) compared to those with low LI.Endocardial LI mappingHystological analysis: Collagen Content

Ablation of hemodynamically unstable ventricular tachycardia guided by ultra-high density pacemapping and PASO correlation map, a multi-center clinical trial

Abstract Background Due to hemodynamic instability during ventricular tachycardia (VT), obtaining a complete electroanatomic map is often difficult if not impossible. Pace-mapping has progressed but still lacks precision and may not reveal sufficient details for complete ablation of the potential critical isthmus. Purpose We hypothesized that a novel strategy of combining ultra-high density (HD) pace-mapping using the PASO algorithm and Carto system to match the induced/clinical VT may aid in the reconstruction of the VT critical isthmus and effective VT ablation leading to reduce the risks of VT recurrence. Methods This was a prospective, multi-center trial conducted between January 2021 and July 2023. We enrolled 30 patients with ischemic heart disease and scar mediated recurrent VT clinically indicated for ablation. Following induction of clinical VT, we performed ultra-HD pace-mapping (5-10 mm distance between pacing points) of the identified ventricular substrate. Using PASO Module, a pacing correlation map (PCM) was constructed based on the percentage match to the induced VT. Using the PCM and the measured stimulation to electrogram intervals, the potential VT critical isthmus was reconstructed. Radiofrequency ablation was carried out to completely transect the delineated isthmus. Post ablation, repeat HD mapping and ablation was performed, until the PASO % correlation dropped from >93% to <70%, indicating at least uni-directional (orthodromic to the perceived VT circuit) conduction block through the ablation line. Follow-up data, including ICD interrogations were collected via chart review. Outcomes were compared to 60 propensity-score matched patients with an ICD who were enrolled in the Ranolazine in High-Risk Patients with Implanted Cardioverter-Defibrillators (RAID) trial who did not undergo VT ablation and served as the control group. The primary endpoint was the first occurrence of any VT at 1-year of follow-up. Results Patients enrolled had a mean age of 69 ± 9 years and 13% were women. Propensity matched patients from the RAID trial had similar baseline clinical characteristics to patients who underwent VT ablation (Table). At 1 year follow up, there was a significantly lower cumulative probability of VT/VF recurrent events in the patients who underwent PCM guided ablation as compared with the control group (17% vs 69%, respectively; log-rank p<0.001 Figure). There were no serious procedure related complications with all patients remaining free of adverse events or death at 30 days. Conclusion Our findings suggest that ablation for unstable or unmappable VT is enhanced by ultra-high density pace-mapping to reconstruct the potential VT circuit and is associated with a significantly lower rate of recurrent VT as compared with patients managed with aggressive and escalating medical therapy.Cumulative probability of ICD therapyBaseline clinical characteristics

Non-invasive assessment of the ventricular tachycardia isthmus during sinus rhythm

Abstract Background The ablation of ventricular tachycardias (VT) presents significant challenges due to the complex and time-consuming approaches involved in identifying arrhythmogenic regions. Combining non-invasive electrocardiographic imaging (ECGI) with endocardial mapping could potentially enhance the efficacy of interventions. Objective To evaluate the capability of ECGI in guiding operators towards areas of VT isthmuses during sinus rhythm. Methods Patients with scar-related VT, confirmed by late gadolinium enhancement cardiac magnetic resonance, were prospectively enrolled. We compared the areas of slowed conduction identified by ECGI with the VT sustaining regions identified endocardially. Simultaneous Electroanatomical Mapping (EAM) and ECGI mapping were performed during VT ablation procedures. In patients in whom a hemodynamically stable VT was maintained, the reentry circuit was mapped endocardially, and the ablation target was identified. The left ventricle was segmented into 9 regions, categorized as either VT-isthmus or non-VT isthmus based on EAM findings. Prior to ablation, local activation times (LAT) and conduction velocity (CV) ECGI sinus maps were computed. Slow conduction was quantified non-invasively by computing different ECGI metrics per region, including the mean and the standard deviation (SD) of LAT and CV, the regional Total Activation Time (rTAT) – time span between the earliest and latest activated nodes–, and the Slow Conduction Velocity (SCV) – the percentage of nodes where velocity falls below 60 cm/s -. Results The study included 20 consecutive patients with ischemic cardiomyopathy who were referred for VT ablation. A total of 21 regions linked to the VT isthmus were identified endocardially in 17 patients (age: 66.1±8.8 years, 94.1% male, left ventricular ejection fraction: 26.4±7.3%). Figure 1 illustrates the correlation between the VT circuit and the ECGI sinus map in two patients with extensive left ventricular fibrosis. ECGI metrics related to VT isthmuses exhibited a higher standard deviation in both LAT (18.1±2.0 vs 9.8±1.2 ms; p=0.001), and CV (50.4±4.7 vs 37.1±2.8 cm/s; p=0.011), and a greater percentage of nodes with slowed conduction (13.7±2.7 vs 7.4±1.6 %; p=0.029), compared to non-VT isthmus regions, Figure 2. Multivariate logistic regression analysis revealed that SD-LAT was the strongest predictor of VT isthmus localization. Conclusion ECGI has demonstrated the capability to pinpoint slowed conduction areas responsible for VT in sinus rhythm, showing promise in planning and guiding VT ablation strategies. This advancement paves the way for further research into using this non-invasive tool to improve risk stratification methods for ventricular arrhythmias.

Novel systematic processing of cardiac magnetic resonance imaging identifies target regions associated with infarct-related ventricular tachycardia

Abstract Introduction In the clinic, complete characterization of reentrant ventricular tachycardia (VT) circuits using classical electrophysiological criteria and state-of-the-art high density mapping during VT is complex, and often cannot be completed because of hemodynamic instability. This common limitation has motivated the implementation of mapping strategies during sinus rhythm or ventricular pacing aiming to identify scar regions associated with VT isthmuses or potential arrhythmogenicity. Complementary imaging-based strategies including advanced analyses of scar tissue characteristics have been also proposed for procedure planning and identification of potential arrhythmogenic regions. However, the most recent expert consensus report on catheter ablation of ventricular arrhythmia highlights the lack of agreement on the preferable signal intensity (SI) cut-off values for assessment of tissue heterogeneity and scar areas on late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) images. The latter makes LGE-CMR imaging processing highly operator-dependent and potentially sensitive to selection bias. Purpose We aimed at developing and validating a systematic processing approach on LGE-CMR images to identify potential VT corridors that may include protected isthmuses associated with VT maintenance. Methods Translational study including 18 pigs with established myocardial infarction and inducible VT undergoing in vivo characterization of the anatomical and functional myocardial substrate associated with VT maintenance. Clinical validation was conducted in a multicenter series of 33 patients with ischemic cardiomyopathy undergoing VT ablation. Three-dimensional CMR-LGE images were processed using systematic scanning of 15 signal intensity cut-off ranges to obtain surface visualization of all potential VT corridors. Analysis and comparisons of imaging and electrophysiological data were performed in individuals with full electrophysiological characterization of the isthmus sites of at least one VT morphology. Results In both the experimental pig model and patients undergoing VT ablation, all the electrophysiologically-defined isthmus sites (n=11 and n=19, respectively) showed overlapping regions with CMR-based potential VT corridors. Such imaging-based VT corridors were less specific than electrophysiologically-guided ablation lesions at functionally relevant isthmus sites (Figure). However, in patients, decreasing from 15 to 7 the number of signal intensity cut-off ranges for systematic imaging processing significantly reduced the area of imaging-based potential VT corridors, without diminishing the capability to detect functionally relevant VT isthmus sites. Conclusions Systematic processing of 3D LGE-CMR images provides unbiased identification of imaging based potential VT corridors that contain functionally relevant protected isthmus sites.

Single-beat mapping during programmed ventricular stimulation identifies infarct-related ventricular tachycardia isthmus sites

Abstract Introduction Complete characterization of reentrant ventricular tachycardia (VT) circuits using classical electrophysiological criteria and high-density mapping during VT is complex. Often, VT episodes cannot be fully characterized because of hemodynamic instability during the mapping procedure. This common limitation has motivated the implementation of mapping strategies during sinus rhythm or ventricular pacing aiming to identify scar regions associated with VT isthmuses or potential arrhythmogenicity. However, these strategies still require time-consuming catheter-based mapping. Purpose We aimed to develop and validate a single-beat mapping strategy during programmed ventricular stimulation (PVS) to identify scar regions associated with VT isthmus sites. We hypothesize that protected VT isthmuses within scar regions are characterized by larger activation time dispersion than surrounding scar areas not related to critical isthmus sites. Methods Experimental study including 16 pigs with established myocardial infarction (MI) in the anterior wall. Ten-to-twelve weeks after MI, pigs underwent left ventricular characterization using 3D late-gadolinium enhancement cardiac magnetic resonance imaging, and further invasive electroanatomical mapping to obtain high-density sequential activation maps during ventricular pacing and VT. High-density maps were compared with single-beat maps using a 64-pole basket catheter positioned in the left ventricle. After VT induction, high-density activation maps in well-tolerated VT episodes were used to identify VT isthmus sites. Simultaneous activation data from the 64-pole basket catheter were also obtained during PVS and VT. Off-line analysis was performed to: (i) validate single-beat activation maps during the baseline drive pacing cycle length (S1), and (ii) identify basket-catheter electrodes with the larger local activation time-dispersion score (LAT-DS) during PVS including up to 4 coupled extrastimuli (S2, S3, S4, S5) (Figure 1). LAT-DS was defined as the normalized product of the LAT of each electrode and the activation dispersion among its neighboring electrodes. Results Basket-catheter based single-beat activation maps during S1 pacing showed high correlation values with high-density sequential activation maps (N=16. R²=0.91). In 7 pigs, the VT isthmus site was fully characterized using high-density activation maps. During any of the coupled extrastimuli of the PVS protocol, basket catheter electrodes colocalizing with documented VT isthmus sites on high-density maps showed higher LAT-DS values compared to surrounding electrodes located on scar or healthy regions. Conversely, LAT values alone could not differentiate scar regions relevant for VT maintenance during PVS protocol (Figure 2). Conclusions Sixty-four pole single-beat activation maps during PVS identify left ventricular scar areas with higher than surrounding LAT-DS values that are associated with VT isthmus sites.Figure 1.Experimental modelFigure 2.A-Example. B-C-Full results

Exploration of peak frequency mapping for ventricular tachycardia ablation. Identification of critical isthmus zones during substrate mapping

Abstract Background/Introduction The ability to classify and differentiate between near field and far-field components of intracardiac signals is a key element in identifying critical arrhythmogenic substrate during ventricular tachycardia (VT) ablation. Near Field algorithms based on omnipolar electrograms enable detection and automation of true localised signals providing unique insights into substrate characteristics. This novel feature identifies localised signal peak frequency (PF) which can be displayed across different voltage ranges. Purpose/Aims The significance of PF mapping in the context of VT ablation is limited and its utility in the identification of the critical diastolic isthmus zone (IZ) is not known. The aim of this study is to explore the utilisation of PF mapping during VT ablation and evaluate whether significant differences in PF occur within areas of interest and critical components of the VT circuit during substrate mapping. Methods All patients underwent VT ablation using the EnSite™ X mapping system with the HDGrid omnipolar mapping catheter. Only cases with both high density sinus rhythm (SR) substrate maps and VT activation maps with clear identification of the IZ were included. VT activation and propagation maps were generated and the diastolic IZ was superimposed onto the SR substrate map. PF analysis was performed retrospectively. Surface area, omnipolar voltage and PF of the maps were measured in the SR substrate maps and co-localised with the critical IZ of the VT circuit as identified in the VT activation maps. Analysis of PF was conducted across different voltage ranges: healthy myocardium (>1.5mV), scar (1.5-0.5mV) and dense scar (0.5-0.1mV). Sensitivity and specificity measurements were made within segments of the IZ and non-isthmus zones and depicted as ROC curves. Results 55 patients underwent VT ablation over a 12-month period, with a total of 18 fulfilling the inclusion criteria. Mean age was 70 (±12.5years) with an average ejection fraction of 36%. The overall PF of the SR substrate maps was 121.85±26.85 Hz, compared to 162.22±46.22Hz within the IZ (p=0.002). Within the low voltage scar region, the overall PF was 120.86±33.24Hz compared to 188.32±81.36Hz within the IZ (p=0.003). No significant difference in PF was observed within healthy myocardium (112.70±52.06 Hz) compared to components of the IZ within the >1.5mV range (157.61±136.11Hz), p=0.207. The AUC for PF within the overall substrate map and co-localisation with the IZ was 0.67, and 0.73 within low voltage zones (<1.5mV). Conclusions PF mapping may identify critical components of the VT circuit during SR substrate mapping and its utilisation may compliment established substrate mapping approaches. PF guided ablation strategies require further evaluation in future prospective studies.

Peak frequency analysis and differentiation between near-field and far-field electrograms of the ventricular tachycardia circuit leads to successful ablation of arrhythmia.

Peak frequency analysis and differentiation between near-field and far-field electrograms of the ventricular tachycardia circuit leads to successful ablation of arrhythmia.

Personalized voltage maps guided by cardiac magnetic resonance in the era of high-density mapping

BackgroundVoltage mapping could identify the conducting channels potentially responsible for ventricular tachycardia (VT). Standard thresholds (0.5–1.5 mV) were established using bipolar catheters. No thresholds have been analyzed with high-density mapping catheters. In addition, channels identified by cardiac magnetic resonance (CMR) has been proven to be related with VT. ObjectiveThe purpose of this study was to analyze the diagnostic yield of a personalized voltage map using CMR to guide the adjustment of voltage thresholds. MethodsAll consecutive patients with scar-related VT undergoing ablation after CMR (from October 2018 to December 2020) were included. First, personalized CMR-guided voltage thresholds were defined systematically according to the distribution of the scar and channels. Second, to validate these new thresholds, a comparison with standard thresholds (0.5–1.5 mV) was performed. Tissue characteristics of areas identified as deceleration zones (DZs) were recorded for each pair of thresholds. In addition, the relation of VT circuits with voltage channels was analyzed for both maps. ResultsThirty-two patients were included [mean age 66.6 ± 11.2 years; 25 (78.1%) ischemic cardiomyopathy]. Overall, 52 DZs were observed: 44.2% were identified as border zone tissue with standard cutoffs vs 75.0% using personalized voltage thresholds (P = .003). Of the 31 VT isthmuses detected, only 35.5% correlated with a voltage channel with standard thresholds vs 74.2% using adjusted thresholds (P = .005). Adjusted cutoff bipolar voltages that better matched CMR images were 0.51 ± 0.32 and 1.79 ± 0.71 mV with high interindividual variability (from 0.14–1.68 to 0.7–3.21 mV). ConclusionPersonalized voltage CMR-guided personalized voltage maps enable a better identification of the substrate with a higher correlation with both DZs and VT isthmuses than do conventional voltage maps using fixed thresholds.

Mechanism of Ventricular Tachycardia Occurring in Chronic Myocardial Infarction Scar.

Cardiac arrest is the leading cause of death in the more economically developed countries. Ventricular tachycardia associated with myocardial infarct is a prominent cause of cardiac arrest. Ventricular arrhythmias occur in 3 phases of infarction: during the ischemic event, during the healing phase, and after the scar matures. Mechanisms of arrhythmias in these phases are distinct. This review focuses on arrhythmia mechanisms for ventricular tachycardia in mature myocardial scar. Available data have shown that postinfarct ventricular tachycardia is a reentrant arrhythmia occurring in circuits found in the surviving myocardial strands that traverse the scar. Electrical conduction follows a zigzag course through that area. Conduction velocity is impaired by decreased gap junction density and impaired myocyte excitability. Enhanced sympathetic tone decreases action potential duration and increases sarcoplasmic reticular calcium leak and triggered activity. These elements of the ventricular tachycardia mechanism are found diffusely throughout scar. A distinct myocyte repolarization pattern is unique to the ventricular tachycardia circuit, setting up conditions for classical reentry. Our understanding of ventricular tachycardia mechanisms continues to evolve as new data become available. The ultimate use of this information would be the development of novel diagnostics and therapeutics to reliably identify at-risk patients and prevent their ventricular arrhythmias.

Catheter Ablation for Ventricular Tachycardia in Patients With Desmoplakin Cardiomyopathy

BackgroundDesmoplakin (DSP) pathogenic/likely pathogenic (P/LP) variants are associated with malignant phenotypes of arrhythmogenic cardiomyopathy (DSP-ACM). Reports of outcomes after ventricular tachycardia (VT) ablation in DSP-ACM are scarce. ObjectivesIn this study, the authors sought to report on long-term outcomes of VT ablation in DSP-ACM. MethodsPatients with P/LP DSP variants at 9 institutions undergoing VT ablation were included. Demographic, clinical, and instrumental data as well as all ventricular arrhythmia (VA) events were collected. Sustained VAs after the index procedure were the primary outcome. A per-patient before and after ablation comparison of rates of VA episodes per year was performed as well. ResultsTwenty-four DSP-ACM patients (39.3 ± 12.1 years of age, 62.5% male, median 6,116 [Q1-Q3: 3,362-7,760] premature ventricular complexes [PVCs] per 24 hours, median 4 [Q1-Q3: 2-11] previous VA episodes per patient at ablation) were included. Index procedure was most commonly endocardial/epicardial (19/24) The endocardium of the right ventricle (RV), the left ventricle (LV), or both ventricles were mapped in 8 (33.3%), 9 (37.5%), and 7 (29.2%) cases, respectively. Low voltage potentials were found in 10 of 15 patients in the RV and 11 of 16 in the LV. Endocardial ablation was performed in 18 patients (75.0%). Epicardial mapping in 19 patients (79.2%) identified low voltage potentials in 17, and 16 received epicardial ablation. Over the following 2.9 years (Q1-Q3: 1.8-5.5 years), 13 patients (54.2%) experienced VA recurrences. A significant reduction in per-patient event/year before and after ablation was observed (1.4 [Q1-Q3: 0.5-2.4] to 0.1 [Q1-Q3: 0.0-0.4]; P = 0.009). Two patients needed heart transplantation, and 4 died (3 of heart failure and 1 noncardiac death). ConclusionsVT ablation in DSP-ACM is effective in reducing the VA burden of the disease, but recurrences are common. Most VT circuits are epicardial, with both LV and RV low voltage abnormalities. Heart failure complicates clinical course and is an important cause of mortality.

Stereotactic radiotherapy for ventricular tachycardia: A study protocol.

Currently, the standard curative treatment for ventricular tachycardia (VT) and ventricular fibrillation (VF) is radiofrequency catheter ablation. However, when the VT circuit is deep in the myocardium, the catheter may not be delivered, and a new, minimally invasive treatment using different energies is desired. This is a protocol paper for a feasibility study designed to provide stereotactic radiotherapy for refractory VT not cured by catheter ablation after at least one catheter ablation. The primary end point is to evaluate the short-term safety of this treatment and the secondary endpoint is to evaluate its efficacy as assessed by the reduction in VT episode. Cyberknife M6 radiosurgery system will be used for treatment, and the prescribed dose to the target will be 25Gy in one fraction. The study will be conducted on three patients. Since catheter ablation is the only treatment option for VT that is covered by insurance in Japan, there is currently no other treatment for VT/VF that cannot be cured by catheter ablation. We hope that this feasibility study will provide hope for patients who are currently under the stress of ICD activation. The study has been registered in the Japan Registry of Clinical Trials (jRCTs042230030).

A comparison of general anesthesia versus monitored anesthesia care during catheter ablation for ventricular tachycardia

Abstract Background Catheter ablation of ventricular tachycardia (VT) may be performed under general anesthesia (GA) or monitored anesthesia care (MAC). There is a paucity of data studying these two sedation strategies with respect to intraprocedural characteristics, and outcomes of VT ablation. Purpose The purpose of this study was to assess the effects of anesthesia techniques on VT inducibility and outcomes. Methods A single-center, retrospective study of patients undergoing catheter ablation for scar-related VT, from 2016-2022, was conducted. Data collected included demographics, comorbidities, medications, relevant laboratory abnormalities, electrocardiograms, echocardiograms, detailed procedural characteristics, and outcomes. Results One hundred sixty-eight patients who underwent a total of 200 VT ablation procedures were included. The patients undergoing GA had a greater burden of comorbidities including congestive heart failure (77.2% vs. 60.9%), hypertension (66.9% vs. 60.0%), atrial arrhythmias (50.7% vs. 43.8%), diabetes mellitus (21.3% vs. 9.4%), chronic kidney disease (44.1% vs. 31.3%), prior stroke (11.8% vs. 10.9%), myocardial infarction (31.6% vs. 29.7%), pre-existing implantable cardioverter-defibrillator (86.8% vs. 71.9%) and had a higher median number of antiarrhythmic drugs at baseline (2 vs. 1) [Figure 1]. There was a greater percentage of patients with non-ischemic cardiomyopathy (58.1% vs. 51.6%) in the GA cohort. The mean left ventricular ejection fraction was not different among the two groups (39.3 ± 13.9 vs. 42.5 ± 15.3). The GA group had more hemodynamic instability at baseline (p < 0.01), and during VT induction (p < 0.01). There was no significant difference in the number of VT induced, or tachycardia cycle length, in each group. Despite higher radiofrequency energy delivery time in the GA group as compared to the MAC group, the GA group had higher VT inducibility post-procedure and were more likely to be discharged on antiarrhythmic drugs. Even though the recurrence of VT was higher in the GA group compared to the MAC group (41.9% vs. 31.3%), the VT-free survival curves were not significantly different by Kaplan-Meier analysis (p=0.19) [Figure 2]. In a multivariate regression analysis, the sedation strategy was not an independent predictor of VT recurrence (p=NS). However, baseline hemodynamic instability was an independent predictor of VT recurrence after accounting for all intraprocedural characteristics (p=0.008). Conclusion Patients undergoing VT ablation under GA have more comorbidities and tend to be on more antiarrhythmic drugs. The GA group had more hemodynamic instability during the procedure and had greater overall VT recurrence, however, not significant in a time-based analysis. The greater overall recurrence in the GA group could be because they represent a sicker population, or the hemodynamics during the procedure preclude adequate ablation of the VT circuit elements.Figure 1Figure 2

Predicting ventricular tachycardia circuits in patients with arrhythmogenic right ventricular cardiomyopathy using genotype-specific heart digital twins.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiac disease that leads to ventricular tachycardia (VT), a life-threatening heart rhythm disorder. Treating ARVC remains challenging due to the complex underlying arrhythmogenic mechanisms, which involve structural and electrophysiological (EP) remodeling. Here, we developed a novel genotype-specific heart digital twin (Geno-DT) approach to investigate the role of pathophysiological remodeling in sustaining VT reentrant circuits and to predict the VT circuits in ARVC patients of different genotypes. This approach integrates the patient's disease-induced structural remodeling reconstructed from contrast-enhanced magnetic-resonance imaging and genotype-specific cellular EP properties. In our retrospective study of 16 ARVC patients with two genotypes: plakophilin-2 (PKP2, n = 8) and gene-elusive (GE, n = 8), we found that Geno-DT accurately and non-invasively predicted the VT circuit locations for both genotypes (with 100%, 94%, 96% sensitivity, specificity, and accuracy for GE patient group, and 86%, 90%, 89% sensitivity, specificity, and accuracy for PKP2 patient group), when compared to VT circuit locations identified during clinical EP studies. Moreover, our results revealed that the underlying VT mechanisms differ among ARVC genotypes. We determined that in GE patients, fibrotic remodeling is the primary contributor to VT circuits, while in PKP2 patients, slowed conduction velocity and altered restitution properties of cardiac tissue, in addition to the structural substrate, are directly responsible for the formation of VT circuits. Our novel Geno-DT approach has the potential to augment therapeutic precision in the clinical setting and lead to more personalized treatment strategies in ARVC.

Predicting ventricular tachycardia circuits in patients with arrhythmogenic right ventricular cardiomyopathy using genotype-specific heart digital twins

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiac disease that leads to ventricular tachycardia (VT), a life-threatening heart rhythm disorder. Treating ARVC remains challenging due to the complex underlying arrhythmogenic mechanisms, which involve structural and electrophysiological (EP) remodeling. Here, we developed a novel genotype-specific heart digital twin (Geno-DT) approach to investigate the role of pathophysiological remodeling in sustaining VT reentrant circuits and to predict the VT circuits in ARVC patients of different genotypes. This approach integrates the patient’s disease-induced structural remodeling reconstructed from contrast-enhanced magnetic-resonance imaging and genotype-specific cellular EP properties. In our retrospective study of 16 ARVC patients with two genotypes: plakophilin-2 (PKP2, n = 8) and gene-elusive (GE, n = 8), we found that Geno-DT accurately and non-invasively predicted the VT circuit locations for both genotypes (with 100%, 94%, 96% sensitivity, specificity, and accuracy for GE patient group, and 86%, 90%, 89% sensitivity, specificity, and accuracy for PKP2 patient group), when compared to VT circuit locations identified during clinical EP studies. Moreover, our results revealed that the underlying VT mechanisms differ among ARVC genotypes. We determined that in GE patients, fibrotic remodeling is the primary contributor to VT circuits, while in PKP2 patients, slowed conduction velocity and altered restitution properties of cardiac tissue, in addition to the structural substrate, are directly responsible for the formation of VT circuits. Our novel Geno-DT approach has the potential to augment therapeutic precision in the clinical setting and lead to more personalized treatment strategies in ARVC.

Efficient Patient-Specific Simulations of Ventricular Tachycardia Based on Computed Tomography-Defined Wall Thickness Heterogeneity

BackgroundElectrophysiological mapping of ventricular tachycardia (VT) is tedious and poorly reproducible. Substrate analysis on imaging cannot explicitly display VT circuits. ObjectivesThis study sought to introduce a computed tomography–based model personalization approach, allowing for the simulation of postinfarction VT in a clinically compatible time frame. MethodsIn 10 patients (age 65 ± 11 years, 9 male) referred for post-VT ablation, computed tomography–derived wall thickness maps were registered to 25 electroanatomical maps (sinus rhythm, paced, and VT). The relationship between wall thickness and electrophysiological characteristics (activation-recovery interval) was analyzed. Wall thickness was then employed to parameterize a fast and tractable organ-scale wave propagation model. Pacing protocols were simulated from multiple sites to test VT induction in silico. In silico VTs were compared to VT circuits mapped clinically. ResultsClinically, 6 different VTs could be induced with detailed maps in 9 patients. The proposed model allowed for fast simulation (median: 6 min/pacing site). Simulations of steady pacing (600 milliseconds) from 100 different sites/patient never triggered any arrhythmia. Applying S1-S2 or S1-S2-S3 induction schemes allowed for the induction of in silico VTs in the 9 of 10 patients who were clinically inducible. The patient who was not inducible clinically was also noninducible in silico. A total of 42 different VTs were simulated (4.2 ± 2 per patient). Six in silico VTs matched a VT circuit mapped clinically. ConclusionsThe proposed framework allows for personalized simulations in a matter of hours. In 6 of 9 patients, simulations show re-entrant patterns matching intracardiac recordings.

Utility of Very High-Output Pacing to Identify VT Circuits in Patients Manifesting Traditionally Inexcitable Scar

BackgroundEntrainment and pace mapping are used to identify critical components (CCs) of ventricular tachycardia (VT) circuits. In patients with dense myocardial scarring, VT circuits may elude capture at standard high pacing outputs (up to 10 mA at a 2-millisecond pulse width). ObjectivesThe purpose of this study was to assess the utility of very high–output pacing (V-HOP, 50 mA at 2 milliseconds) for identifying CCs of VT circuits after standard high pacing output failed to elicit capture in densely scarred myocardial tissue. MethodsOur standard VT ablation approach included electroanatomic mapping for substrate characterization and entrainment and/or pace mapping to identify CCs of VT circuits. Patients that required V-HOP to capture sites of interest comprised the study cohort. Ablation endpoints were VT termination and noninducibility. ResultsTwenty-five patients (71 ± 10 years of age, all males) undergoing 26 VT ablations met the inclusion criteria. The mean left ventricular ejection fraction was 30% ± 14%, and 85% had ischemic cardiomyopathy. V-HOP was used to successfully entrain VT in 17 patients, yielding central isthmus sites in 10 and entrance/exit sites in 4. VT terminated with radiofrequency ablation at these sites in 15 patients. In 9 patients, V-HOP identified scar locations with a delayed exit. Acute procedural success was achieved in 24 patients without any adverse events. Over a follow-up period of 16 ± 21 months, 2 patients experienced VT recurrence requiring repeat ablation during which the same location was targeted successfully in 1 patient. ConclusionsIn VT patients with a dense scar that is traditionally inexcitable, V-HOP can identify CCs of the re-entrant circuit and guide successful ablation.

Guiding ablation strategies for ventricular tachycardia in patients with structural heart disease by analyzing links and conversion patterns of traceable abnormal late potential zone.

Substrate-based ablation can treat uninducible or hemodynamically instability scar-related ventricular tachycardia (VT). However, whether a correlation exists between the critical VT isthmus and late activation zone (LAZ) during sinus rhythm (SR) is unknown. To demonstrate the structural and functional properties of abnormal substrates and analyze the link between the VT circuit and abnormal activity during SR. Thirty-six patients with scar-related VT (age, 50.0 ± 13.7 years and 86.1% men) who underwent VT ablation were reviewed. The automatic rhythmia ultrahigh resolution mapping system was used for electroanatomic substrate mapping. The clinical characteristics and mapping findings, particularly the LAZ characteristics during SR and VT, were analyzed. To determine the association between the LAZ during the SR and VT circuits, the LAZ was defined as five activation patterns: entrance, exit, core, blind alley, and conduction barrier. Forty-five VTs were induced in 36 patients, 91.1% of which were monomorphic. The LAZ of all patients was mapped during the SR and VT circuits, and the consistency of the anatomical locations of the LAZ and VT circuits was analyzed. Using the ultrahigh resolution mapping system, interconversion patterns, including the bridge, T, puzzle, maze, and multilayer types, were identified. VT ablation enabled precise ablation of abnormal late potential conduction channels. Five interconversion patterns of the LAZ during the SR and VT circuits were summarized. These findings may help formulate more precise substrate-based ablation strategies for scar-related VT and shorter procedure times.

Identification of Human Ventricular Tachycardia Demarcated by Fixed Lines of Conduction Block in a 3-Dimensional Hyperboloid Circuit.

The circuit boundaries for reentrant ventricular tachycardia (VT) have been historically conceptualized within a 2-dimensional (2D) construct, with their fixed or functional nature unresolved. This study aimed to examine the correlation between localized lines of conduction block (LOBs) evident during baseline rhythm with lateral isthmus boundaries that 3-dimensionally constrain the VT isthmus as a hyperboloid structure. A total of 175 VT activation maps were correlated with isochronal late activation maps during baseline rhythm in 106 patients who underwent catheter ablation for scar-related VT from 3 centers (42% nonischemic cardiomyopathy). An overt LOB was defined by a deceleration zone with split potentials (≥20 ms isoelectric segment) during baseline rhythm. A novel application of pacing within deceleration zone (≥600 ms) was implemented to unmask a concealed LOB not evident during baseline rhythm. LOBs identified during baseline rhythm or pacing were correlated with isthmus boundaries during VT. Among 202 deceleration zones analyzed during baseline rhythm, an overt LOB was evident in 47%. When differential pacing was performed in 38 deceleration zones without overt LOBs, an underlying concealed LOB was exposed in 84%. In 152 VT activation maps (2D=53, 3-dimensional [3D]=99), 69% of lateral boundaries colocalized with an LOB in 2D activation patterns, and the depth boundary during 3D VT colocalized with an LOB in 79%. In VT circuits with isthmus regions that colocalized with a U-shaped LOB (n=28), the boundary invariably served as both lateral boundaries in 2D and 3D. Overall, 74% of isthmus boundaries were identifiable as fixed LOBs during baseline rhythm or differential pacing. The majority of VT circuit boundaries can be identified as fixed LOBs from intrinsic or paced activation during sinus rhythm. Analysis of activation while pacing within the scar substrate is a novel technique that may unmask concealed LOBs, previously interpreted to be functional in nature. An LOB from the perspective of a myocardial surface is frequently associated with intramural conduction, supporting the existence of a 3D hyperboloid VT circuit structure. Catheter ablation may be simplified to targeting both sides around an identified LOB during sinus rhythm.

Stereotactic radiotherapy for ventricular tachycardia: A study protocol

Background: Currently, the standard curative treatment for ventricular tachycardia (VT) and ventricular fibrillation (VF) is radiofrequency catheter ablation. However, when the VT circuit is deep in the myocardium, the catheter may not be delivered, and a new, minimally invasive treatment using different energies is desired. Methods: This is a protocol paper for a feasibility study designed to provide stereotactic radiotherapy for refractory VT not cured by catheter ablation after at least one catheter ablation. The primary end point is to evaluate the short-term safety of this treatment and the secondary endpoint is to evaluate its efficacy as assessed by the reduction in VT episode. Cyberknife M6 radiosurgery system will be used for treatment, and the prescribed dose to the target will be 25Gy in one fraction. The study will be conducted on three patients. Conclusion: Since catheter ablation is the only treatment option for VT that is covered by insurance in Japan, there is currently no other treatment for VT/VF that cannot be cured by catheter ablation. We hope that this feasibility study will provide hope for patients who are currently under the stress of ICD activation. Trial registration: The study has been registered in the Japan Registry of Clinical Trials (jRCTs042230030).