Re-entry Vulnerability Index Research Articles

Identification of reentry vulnerable targets during substrate mapping for ablation in scar related VT: the "visual" reentry vulnerability index

Abstract Introduction Conduction abnormalities including zones of deceleration (DZ) & late activation are functionally important targets for ablation in scar-related ventricular tachycardias (VT). Repolarisation heterogeneities are equally important but are not routinely assessed. Visualisation of a combination of both conduction & repolarisation metrics whilst in sinus in the form of a re-entry vulnerability index (RVI) may enable more precise identification of critical ablation targets. Rationale: To test accuracy of a novel functional substrate mapping strategy combining conduction & repolarisation metrics to "visually" estimate reentry vulnerability sites (RVIv) during scar related VT ablation without the need for offline processing required for "computational" RVI. Methods VT cases using a multipolar grid-catheter for contact mapping were reviewed. DZ &areas of late activation were tagged on omnipolar LAT substrate maps. The corresponding unipolar repolarisation maps depicting local repolarisation time (LRT) based on the Wyatt method (WOI over T-Wave annotating to +dV/dt, UEGM-Filter 0.05-100Hz) were then displayed side-by-side with the LAT map. Timing reference was set to onset of surface QRS. Colour scale of LRT maps was set to start at or ahead of the timing of latest LAT. "Visual RVI" zones were identified if the tagged zone of late activation was overlapping and/or directly adjacent to an area of "early" repolarisation (defined as before or within 100ms of latest LAT point) based on colour. In visually identified RVI areas, temporal (timing difference in ms) & spatial relationship (distance in mm) of EGMs with earliest RT (RTe) to EGM with latest AT (ATL) separated by max. 20mm were measured & RVI calculated (RTe subtracted by ATL). Number of RVIv zones per map, RVI metrics & distance from closest RVI to VT Exit site (defined per activation±entrainment or pace mapping) were assessed. The lower/negative the numeric RVI, the higher the vulnerability for reentry. Results 20 patients with scar-related reentry VT were included (90% male, 63.8±11.6 years, LVEF 36±16%, 60% ischemic/40% non-ischemic). LAT & LRT map point counts were 4835±2625 and 3596±2805. In 17 (85%) patients at least 1 RVIv zone was identified, with on avg. 3.3±1.7 RVIv zones/patient. Manual RVIs were calculated to 10.4±78.9ms ( "most vulnerable" RVI was -227ms) with on avg. 9.5±5.3mm distance between RTe & ATL. All maps with no RVIv zone on the mapped surface were of non-ischemic etiology. The shortest distance of RVIs to functionally critical sites during VT was 8.9±7.4mm (range 0-33mm). Conclusion Visual reentry vulnerability estimation based on a combination of established conduction and novel repolarisation maps is feasible & may help to identify functionally critical zones during substrate mapping. Future efforts should include dedicated automated repolarisation mapping tools to facilitate integration of repolarisation dynamics in functional VT substrate mapping workflows.Figure 1Example Visual RVI Mapping

Unexpected impairment of INa underpins reentrant arrhythmias in a knock-in swine model of Timothy syndrome

Timothy syndrome 1 (TS1) is a multi-organ form of long QT syndrome associated with life-threatening cardiac arrhythmias, the organ-level dynamics of which remain unclear. In this study, we developed and characterized a novel porcine model of TS1 carrying the causative p.Gly406Arg mutation in CACNA1C, known to impair CaV1.2 channel inactivation. Our model fully recapitulated the human disease with prolonged QT interval and arrhythmic mortality. Electroanatomical mapping revealed the presence of a functional substrate vulnerable to reentry, stemming from an unforeseen constitutional slowing of cardiac activation. This signature substrate of TS1 was reliably identified using the reentry vulnerability index, which, we further demonstrate, can be used as a benchmark for assessing treatment efficacy, as shown by testing of multiple clinical and preclinical anti-arrhythmic compounds. Notably, in vitro experiments showed that TS1 cardiomyocytes display Ca2+ overload and decreased peak INa current, providing a rationale for the arrhythmogenic slowing of impulse propagation in vivo.

Computational Re-Entry Vulnerability Index Mapping to Guide Ablation in Patients With Postmyocardial InfarctionVentricular Tachycardia.

Ventricular tachycardias (VTs) in patients with myocardial infarction (MI) are often treated with catheter ablation. However, the VT induction during this procedure does not always identify all of the relevant activationpathways or may not be possible or tolerated. The re-entry vulnerability index (RVI) quantifies regional activation-repolarization differences and can detect multiple regions susceptible to re-entry without the need to inducethe arrhythmia. This study aimed to further develop and validate the RVI mapping in patient-specific computational models of post-MI VTs. Cardiac magnetic resonance imaging data from 4 patients with post-MI VTs were used to induce VTs inacomputational electrophysiological model by pacing. The RVI map of a premature beat in each patient modelwasused to guide virtual ablations. We compared our results with those of clinical ablation in the same patients. Single-site virtual RVI-guided ablation prevented VT induction in 3 of 9 cases. Multisite virtual ablations guided by RVI mapping successfully prevented re-entry in all cases (9 of 9). Overall, virtual ablation required 15-fold fewer ablation sites (235.5 ± 97.4 vs 17.0 ± 6.8) and 2-fold less ablation volume (5.34 ± 1.79mL vs 2.11 ± 0.65mL) than the clinical ablation. RVI mapping allows localization of multiple regions susceptible to re-entry and may help guide VT ablation. RVI mapping does not require the induction of arrhythmia and may result in less ablated myocardial volumeswith fewer ablation sites.

PO-709-03 THE APPLICATION OF THE RE-ENTRY VULNERABILITY INDEX TO DETERMINE VENTRICULAR TACHYCARDIA EXIT FROM DIFFERENT PACING LOCATIONS, IN A PORCINE INFARCT MODEL

The application of high-density electroanatomic (EA) and functional mapping strategies is a new frontier in ventricular tachycardia (VT) ablation. There is no definitive method to identify arrhythmogenic substrate, and ablation outcomes remain suboptimal. The re-entry vulnerability index (RVI) integrates unipolar activation and repolarisation timing, and low RVI values correlate with vulnerable sites of re-entrant VT origin.

Assessing the ability of substrate mapping techniques to guide ventricular tachycardia ablation using computational modelling

BackgroundIdentification of targets for ablation of post-infarction ventricular tachycardias (VTs) remains challenging, often requiring arrhythmia induction to delineate the reentrant circuit. This carries a risk for the patient and may not be feasible. Substrate mapping has emerged as a safer strategy to uncover arrhythmogenic regions. However, VT recurrence remains common. GoalTo use computer simulations to assess the ability of different substrate mapping approaches to identify VT exit sites. MethodsA 3D computational model of the porcine post-infarction heart was constructed to simulate VT and paced rhythm. Electroanatomical maps were constructed based on endocardial electrogram features and the reentry vulnerability index (RVI - a metric combining activation (AT) and repolarization timings to identify tissue susceptibility to reentry). Since scar transmurality in our model was not homogeneous, parameters derived from all signals (including dense scar regions) were used in the analysis. Potential ablation targets obtained from each electroanatomical map during pacing were compared to the exit site detected during VT mapping. ResultsSimulation data showed that voltage cut-offs applied to bipolar electrograms could delineate the scar, but not the VT circuit. Electrogram fractionation had the highest correlation with scar transmurality. The RVI identified regions closest to VT exit site but was outperformed by AT gradients combined with voltage cut-offs. The performance of all metrics was affected by pacing location. ConclusionsSubstrate mapping could provide information about the infarct, but the directional dependency on activation should be considered. Activation-repolarization metrics have utility in safely identifying VT targets, even with non-transmural scars.

221Evaluating the ability of different substrate mapping techniques to identify scar-related ventricular tachycardia circuits using computational modelling

Abstract Funding Acknowledgements National Institute for Health Research; British Heart Foundation; and The Wellcome Trust and Engineering and Physical Sciences Research Council. Background Accurate identification of targets for catheter ablation therapy of ventricular tachycardias (VTs) in the postinfarction heart remains a significant challenge. Identification of such targets often requires VT-induction to delineate the entry/exit points of the reentrant circuit sustaining the VT. However, inducibility may not be possible due to hemodynamic instability. In this scenario, substrate ablation strategies can still be performed to uncover the arrhythmogenic substrate during sinus or paced rhythm. However, substrate mapping may fail to accurately delineate the reentrant circuit resulting in VT recurrence after the procedure. Purpose To use computer simulations to compare the ability of different electroanatomical maps constructed following typical substrate ablation strategies to identify the VT exit site. Methods An image-based computational model of the porcine post-infarction left ventricle was constructed to simulate VT and paced rhythm. Electroanatomical maps were constructed based on the following features extracted from electrograms computed on the endocardial surface: activation time (AT), bipolar electrogram amplitude, signal fractionation and the reentry vulnerability index (RVI - a metric combining activation and repolarization timings to identify tissue susceptibility to reentry). Potential ablation targets during substrate mapping were compared for: highest 5% AT gradient; lowest 5% bipolar signal amplitudes; areas with fragmented signals (more than one peak); and lowest 5% RVI. The minimum distance, d, between the manually identified VT exit site and the targets was measured. Results The RVI performed better than the other metrics at detecting the VT exit site (see Figure). The minimum distance between sites of lowest RVI and the exit site was 3.2mm compared to 13.1mm and 15.9mm in traditional AT and voltage maps, respectively. As the scar was not transmural, parameters derived from all electrograms (including those located on dense scar regions) were used to construct the electroanatomical maps. This improved the performance of the RVI significantly, making it more specific than the other metrics as can be seen in the Figure. Conclusions Among all metrics investigated here, the RVI identified the vulnerable region closest to VT exit site. This finding suggests that activation-repolarization metrics may improve the detection of pro-arrhythmic regions without having to induce VT. Moreover, the RVI may be particularly well suited for detecting vulnerable regions within non-transmural scars. Abstract Figure. VT and Substrate Mapping

Evaluation of the reentry vulnerability index to predict ventricular tachycardia circuits using high-density contact mapping

BackgroundIdentifying arrhythmogenic sites to improve ventricular tachycardia (VT) ablation outcomes remains unresolved. The reentry vulnerability index (RVI) combines activation and repolarization timings to identify sites critical for reentrant arrhythmia initiation without inducing VT.ObjectiveThe purpose of this study was to provide the first assessment of RVI’s capability to identify VT sites of origin using high-density contact mapping and comparison with other activation-repolarization markers of functional substrate.MethodsEighteen VT ablation patients (16 male; 72% ischemic) were studied. Unipolar electrograms were recorded during ventricular pacing and analyzed offline. Activation time (AT), activation–recovery interval (ARI), and repolarization time (RT) were measured. Vulnerability to reentry was mapped based on RVI and spatial distribution of AT, ARI, and RT. The distance from sites identified as vulnerable to reentry to the VT site of origin was measured, with distances <10 mm and >20 mm indicating accurate and inaccurate localization, respectively.ResultsThe origins of 18 VTs (6 entrainment, 12 pace-mapping) were identified. RVI maps included 1012 (408–2098) (median, 1st–3rd quartiles) points per patient. RVI accurately localized 72.2% VT sites of origin, with median distance of 5.1 (3.2–10.1) mm. Inaccurate localization was significantly less frequent for RVI than AT (5.6% vs 33.3%; odds ratio 0.12; P = .035). Compared to RVI, distance to VT sites of origin was significantly larger for sites showing prolonged RT and ARI and were nonsignificantly larger for sites showing highest AT and ARI gradients.ConclusionRVI identifies vulnerable regions closest to VT sites of origin. Activation-repolarization metrics may improve VT substrate delineation and inform novel ablation strategies.

Characterizing the clinical implementation of a novel activation-repolarization metric to identify targets for catheter ablation of ventricular tachycardias using computational models

Identification of targets for catheter ablation of ventricular tachycardias (VTs) remains a significant challenge. VTs are often driven by re-entrant circuits resulting from a complex interaction between the front (activation) and tail (repolarization) of the electrical wavefront. Most mapping techniques do not take into account the tissue repolarization which may hinder the detection of ablation targets. The re-entry vulnerability index (RVI), a recently proposed mapping procedure, incorporates both activation and repolarization times to uncover VT circuits. The method showed potential in a series of experiments, but it still requires further development to enable its incorporation into a clinical protocol. Here, in-silico experiments were conducted to thoroughly assess RVI maps constructed under clinically-relevant mapping conditions. Within idealized as well as anatomically realistic infarct models, we show that parameters of the algorithm such as the search radius can significantly alter the specificity and sensitivity of the RVI maps. When constructed on sparse grids obtained following various placements of clinical recording catheters, RVI maps can identify vulnerable regions as long as two electrodes were placed on both sides of the line of block. Moreover, maps computed during pacing without inducing VT can reveal areas of abnormal repolarization and slow conduction but not directly vulnerability. In conclusion, the RVI algorithm can detect re-entrant circuits during VT from low resolution mapping grids resembling the clinical setting. Furthermore, RVI maps may provide information about the underlying tissue electrophysiology to guide catheter ablation without the need of inducing potentially harmful VT during the clinical procedure. Finally, the ability of the RVI maps to identify vulnerable regions with specificity in high resolution computer models could potentially improve the prediction of optimal ablation targets of simulation-based strategies.

Assessment of a conduction-repolarisation metric to predict Arrhythmogenesis in right ventricular disorders

BackgroundThe re-entry vulnerability index (RVI) is a recently proposed activation-repolarization metric designed to quantify tissue susceptibility to re-entry. This study aimed to test feasibility of an RVI-based algorithm to predict the earliest endocardial activation site of ventricular tachycardia (VT) during electrophysiological studies and occurrence of haemodynamically significant ventricular arrhythmias in follow-up. MethodsPatients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) (n = 11), Brugada Syndrome (BrS) (n = 13) and focal RV outflow tract VT (n = 9) underwent programmed stimulation with unipolar electrograms recorded from a non-contact array in the RV. ResultsLowest values of RVI co-localised with VT earliest activation site in ARVC/BrS but not in focal VT. The distance between region of lowest RVI and site of VT earliest site (Dmin) was lower in ARVC/BrS than in focal VT (6.8 ± 6.7 mm vs 26.9 ± 13.3 mm, p = 0.005). ARVC/BrS patients with inducible VT had lower Global-RVI (RVIG) than those who were non-inducible (−54.9 ± 13.0 ms vs −35.9 ± 8.6 ms, p = 0.005) or those with focal VT (−30.6 ± 11.5 ms, p = 0.001). Patients were followed up for 112 ± 19 months. Those with clinical VT events had lower Global-RVI than both ARVC and BrS patients without VT (−54.5 ± 13.5 ms vs −36.2 ± 8.8 ms, p = 0.007) and focal VT patients (−30.6 ± 11.5 ms, p = 0.002). ConclusionsRVI reliably identifies the earliest RV endocardial activation site of VT in BrS and ARVC but not focal ventricular arrhythmias and predicts the incidence of haemodynamically significant arrhythmias. Therefore, RVI may be of value in predicting VT exit sites and hence targeting of re-entrant arrhythmias.

83Use of ECGi and re-entry vulnerability index to predict VT Re-entry sites in sinus rhythm

83Use of ECGi and re-entry vulnerability index to predict VT Re-entry sites in sinus rhythm

32 Global high density mapping of re-entry vulnerability index aids risk stratification and identifies sites of arrhythmia initiation in brugada syndrome and arvc

Introduction Initiation of reentrant ventricular tachycardia (VT) involves complex interactions between activation (AT) and repolarization times (RT). Recently, an algorithm has been developed to generate a spatial map (designated the re-entry vulnerability index-RVI) from intervals between local ATs and RTs at adjacent points over a multielectrode grid. The algorithm has been shown to accurately identify the region of a macro-reentrant circuit in two animal models (1). The aim of this study was to test the feasibility of RVI mapping in the right ventricle (RV) to aid ablation strategy of reentrant arrhythmias. Methods Patients with Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) (n=10), Brugada Syndrome (BrS) (n=14) and normal heart RV outflow tract (RVOT) VT (n=6) underwent electrophysiological studies and were followed up for 113±21 months post procedure. Unipolar electrograms were recorded from a non-contact array (St Jude Medical) placed in the RVOT and geometry created with the Ensite system. Recordings were made during a programmed electrical stimulation protocol consisting of a 600 ms drive train and S2 extras. ATs and RTs were computed from the unipolar electrograms and the RVI calculated as previously described (1). Minimum 10% of global RVI values corrected for cycle length ( RVI c 10% ) and distance between region of lowest 5% of RVI values and region of earliest activation during VT ( D min ) were computed for each patient. Results Shortest values of RVI, which represent sites of highest susceptibility to re-entry, co-localised with earliest activation point during VT in the 9 patients with ARVC/BrS where VT was initiated (figure 1). In the ARVC patients this corresponded with location of RV scar as seen on MRI. In the 6 patients with normal heart focal VT, regions of lowest RVI did not co-localise with VT origin. Distance between region of lowest RVI and region of earliest activation during VT, D min , was significantly lower in BrS and ARVC than in normal heart VT (Fig 2A). In both ARVC patients D min =0, indicating region of lowest RVI overlapped with region of earliest VT activation. Of the patients with ARVC/BrS, those with inducible VT or clinical VT at follow-up had significantly lower minimum values of RVI c than those without (−61.0±13.8 ms vs −37.1±7.1 ms) (Fig 2B). Patients with normal heart VT had highest values of RVI c (−27.0±11.3 ms). Conclusion An algorithm based on relative local ATs and RTs identifies localised regions of high susceptibility to conduction block and re-entry, with lowest RVI values localising VT origin of reentrant but not focal arrhythmias. This index could be applied to: 1. Risk stratify ARVC/BrS patients to target ICD prophylaxis. 2. Target ablation for reentrant arrhythmias which are difficult to induce or are haemodynamically unstable, without need for arrhythmia initiation. Reference . Child Net al. Heart Rhythm2015;12:1644–1653

Investigating a Novel Activation-Repolarisation Time Metric to Predict Localised Vulnerability to Reentry Using Computational Modelling

Exit sites associated with scar-related reentrant arrhythmias represent important targets for catheter ablation therapy. However, their accurate location in a safe and robust manner remains a significant clinical challenge. We recently proposed a novel quantitative metric (termed the Reentry Vulnerability Index, RVI) to determine the difference between activation and repolarisation intervals measured from pairs of spatial locations during premature stimulation to accurately locate the critical site of reentry formation. In the clinic, the method showed potential to identify regions of low RVI corresponding to areas vulnerable to reentry, subsequently identified as ventricular tachycardia (VT) circuit exit sites. Here, we perform an in silico investigation of the RVI metric in order to aid the acquisition and interpretation of RVI maps and optimise its future usage within the clinic. Within idealised 2D sheet models we show that the RVI produces lower values under correspondingly more arrhythmogenic conditions, with even low resolution (8 mm electrode separation) recordings still able to locate vulnerable regions. When applied to models of infarct scars, the surface RVI maps successfully identified exit sites of the reentrant circuit, even in scenarios where the scar was wholly intramural. Within highly complex infarct scar anatomies with multiple reentrant pathways, the identified exit sites were dependent upon the specific pacing location used to compute the endocardial RVI maps. However, simulated ablation of these sites successfully prevented the reentry re-initiation. We conclude that endocardial surface RVI maps are able to successfully locate regions vulnerable to reentry corresponding to critical exit sites during sustained scar-related VT. The method is robust against highly complex and intramural scar anatomies and low resolution clinical data acquisition. Optimal location of all relevant sites requires RVI maps to be computed from multiple pacing locations.

Dispersion in ventricular repolarization in the human, canine and porcine heart

Dispersion in repolarization is important for the genesis of the T wave, and for the induction of reentrant arrhtyhmias. Because the T wave differs across species our intent here is to review the epicardial, endocardial and transmural repolarization patterns contributing to repolarization in whole hearts from man, dog and pig. The major points we emphasize are: transmural repolarization time gradients are small and are directed from endocardium (early) to epicardium (late) in dog and human and from epicardium to endocardium in pig; the right ventricle tends to repolarize before the left ventricle and this difference is larger in dog than in pig; a negative relation between the activation times and the repolarization times is rare in man, and absent in dog and pig. Given the above, a large dispersion in repolarization between two myocardial areas does not lead to arrhythmias without a premature beat. Moreover, an arrhythmic substrate can be identified by a metric composed of activation times and repolarization times, the reentry vulnerability index, RVI.

An activation-repolarization time metric to predict localized regions of high susceptibility to reentry.

Initiation of reentrant ventricular tachycardia (VT) involves complex interactions between front and tail of the activation wave. Recent experimental work has identified the time interval between S2 repolarization proximal to a line of functional block and S2 activation at the adjacent distal side as a critical determinant of reentry. We hypothesized that (1) an algorithm could be developed to generate a spatial map of this interval ("reentry vulnerability index" [RVI]), (2) this would accurately identify a site of reentry without the need to actually induce the arrhythmia, and (3) it would be possible to generate an RVI map in patients during routine clinical procedures. An algorithm was developed that calculated RVI between all pairs of electrodes within a given radius. The algorithm successfully identified the region with increased susceptibility to reentry in an established Langendorff pig heart model and the site of reentry and rotor formation in an optically mapped sheep ventricular preparation and computational simulations. The feasibility of RVI mapping was evaluated during a clinical procedure by coregistering with cardiac anatomy and physiology of a patient undergoing VT ablation. We developed an algorithm to calculate a reentry vulnerability index from intervals between local repolarization and activation. The algorithm accurately identified the region of reentry in 2 animal models of functional reentry. The clinical application was demonstrated in a patient with VT and identified the area of reentry without the need of inducing the arrhythmia.