Reentrant Ventricular Tachycardia Research Articles

Impact of Multidirectional Pacing on Activation and Repolarization Parameters to Localize Ischemic Ventricular Tachycardia Circuits.

In ventricular tachycardia (VT), optimal substrate mapping strategies identifying arrhythmogenic sites are not established. This study sought to evaluate multidirectional pacing on the distribution of specific conduction and repolarization metrics to localize re-entrant VT sites in a porcine infarct model. Substrate maps were created in 13 pigs with chronic myocardial infarction using the Advisor HD Grid (Abbott) during right ventricular (RV), left ventricular, biventricular pacing (BIV), and sinus rhythm (SR). Critical VT sites of early-, mid-, and late-diastolic signals were delineated. Vulnerable sites to re-entry were defined as sites of latest activation timing within and post-QRS complex, largest activation and activation-recovery interval gradients. Distances between the 20 most vulnerable sites and diastolic VT points were measured, and identification of VT points was assessed using the area under the receiver-operating characteristic curve. A total of 34 VTs were mapped, and 48 sinus and pacing maps were obtained (10 BIV, 13 left ventricular, 13 RV, 12 SR). Late potential mapping in SR was taken as the established clinical standard for comparison. Latest activation time with BIV pacing provided the closest localization for VT isthmus (median 5.5mm; IQR: 7.15mm; P< 0.005). The gradient of activation-recovery interval using RV pacing had closest localization for VT exit and entrance (median 10.6mm; IQR: 5.0mm; P< 0.005 and 9.4mm; IQR: 8.0mm; P< 0.05). Global sensitivity and specificity analysis showed that gradient of activation-recovery interval in SR achieved the highest area under the receiver-operating characteristic curve, with similar results from the gradient of activation timing. Multidirectional pacing in combination with conduction and repolarization parameters enables better localization of VT diastolic critical sites vs SR late potentials.

Localized three-dimensional reentrant ventricular tachycardia visualized by high-density mapping in arrhythmogenic right ventricular cardiomyopathy.

Localized three-dimensional reentrant ventricular tachycardia visualized by high-density mapping in arrhythmogenic right ventricular cardiomyopathy.

Wavefront curvature analysis derived from preprocedural imaging can identify the critical isthmus in patients with postinfarcted ventricular tachycardia

BackgroundWhere activation wavefront curvature is convexly shaped, functional conduction block can occur. ObjectiveThe purpose of this study was to determine whether left ventricular (LV) wall thickness determined from contrast-enhanced computed tomography (CT) is useful in localizing such areas in clinical postinfarction reentrant ventricular tachycardia (VT). MethodsWe evaluated data from 6 patients who underwent catheter ablation for postinfarction VT. CT imaging with inHEART processing was conducted 1–3 days before electrophysiological (EP) study to determine LV wall thickness (T). Activation wavefront curvature was approximated as ΔT/T, where ΔT represents wall thickness change. During EP study, bipolar LV VT electrograms were acquired using a high-density mapping catheter, and activation times were determined. Maps of T, ΔT/T, and VT activation were subsequently compared using statistical analyses. ResultsTwo of 6 cases exhibited dual circuit morphologies, resulting in a total of 8 VT morphologies analyzed. The LV wall near the VT isthmus location tended to be thin, on the order of a few hundred micrometers. Regions of largest ΔT/T partially coincided with the lateral isthmus boundaries where electrical conduction block occurred during VT. ΔT/T at the boundaries, measured from imaging, was significantly larger compared to values at the isthmus midline and to the global LV mean value (P <.001). ConclusionWavefront curvature measured by ΔT/T and caused by source–sink mismatch is dependent on ventricular wall thickness. Areas of high wavefront curvature partly coincide with and may be helpful in locating the VT isthmus in infarct border zones using preprocedural imaging analysis.

Targeting Wavefront Discontinuity Lines for Scar-Related Ventricular Tachycardia Ablation: A Novel Functional Substrate Ablation Approach

BackgroundThe boundaries of critical isthmuses for re-entrant ventricular tachycardia (VT) are formed by wavefront discontinuities (fixed lines of block, slow propagation, and rotational propagation) seen during baseline rhythm. It is unknown whether wavefront discontinuities can be automatically identified and targeted for ablation using electroanatomic mapping systems. ObjectivesThe purpose of this study was to assess the electrophysiologic characteristics of automatically projected wavefront discontinuity lines (WADLs) and outcomes of an ablation strategy targeting WADLs in a mixed cohort of VT patients. MethodsLate activation substrate maps were analyzed from 1 or more baseline rhythm wavefronts. WADLs were identified using the Carto Extended Early Meets Late module. Number, total length, and distance to critical VT sites were measured. VT recurrence and VT-free survival were followed. ResultsIn total, 49 patients underwent 52 ablations with 71 unique substrate maps analyzed (18.8% epicardial; 62.0% right ventricular paced, 28.2% sinus rhythm, 9.9% left ventricular paced). A total of 28 VT critical sites were identified in 24 patients. WADLs were present in 49 of 71 (69.0%) maps. WADLs were present regardless of cardiomyopathy etiology, mapping wavefront, or surface. At a WADL threshold of 30%, 73.9% of critical VT sites were in close proximity (≤15 mm) to a WADL. VT-free survival was 62% at 1 year, with a competing risk model estimating a 1-year risk of VT recurrence of 23%. ConclusionsWADLs can be automatically projected in a majority of patients in a mixed cohort of cardiomyopathy etiology, mapped wavefronts, and myocardial surfaces mapped. Targeting WADLs results in low rate of VT recurrence at 1 year.

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

The evaluation of the efficacy of automated peak frequency annotation algorithm for the identification of critical isthmus of ventricular tachycardia and deceleration zones

Abstract Background Substrate modification techniques have widely been adopted due to hemodynamic instability and non-inducibility of clinical ventricular tachycardia (VT). Accurate annotation of local near field EGMs is paramount to better evaluate the ventricular substrate. Furthermore, annotation of late potentials (LP) necessitates substantial manual input and isochronal late activation mapping (ILAM) involves constant sensitivity adjustments, potentially affecting the accuracy of local ventricular signal representation. Objective This study aims to assess the utility of novel automated peak frequency (PF), which aims to determine near field local activity in low voltage regions in the prediction of the CI of scar related reentrant VTs. Furthermore, the effectiveness of automated PF annotation of near field EGMs to identify deceleration zone (DZ) during ILAM was also evaluated. Methods A total of 18 patients with scar-related VT were analyzed. In all patients, VT isthmuses were identified based on activation maps and acute termination achieved during radiofrequency ablation. Automated PF annotation using Ensite X system (Abbott) was retrospectively performed in all cases specifically in areas of low voltage with fractioned signals. The accuracy of applying the PF value and automated ILAM map for detecting VT isthmus was also assessed. Results Among the study group, 12 (66.7%) had ischemic cardiomyopathy, while 6 (33.3%) had nonischemic cardiomyopathy [3 (16.7%) with arrhythmogenic right ventricular cardiomyopathy, 2 (11.1%) with idiopathic dilated cardiomyopathy, and 1 (5.6%) with hypertrophic cardiomyopathy]. All identified isthmuses were located in areas exhibiting bipolar voltage below 0.5 mV and a PF of 250 Hz with fractionated EGMs Automated NF DZ annotation predicted the VT isthmus in 16/18 (88.9%) of the cases similar to the conventional ILAM with manual adjustment (88.9%). Conclusion Using high-density electroanatomical mapping with near field algorithm, a PF cutoff of 250 Hz accurately identified the low voltage regions to predict the CI of VT. In addition, automated annotation of EGMs during ILAM similarly identified the DZs compared with conventional last deflection algorithm with manual adjustments, which were colocalized with CI of VTs.

Bundle branch reentrant ventricular tachycardia in a patient with Fabry disease

BackgroundBundle branch reentrant ventricular tachycardia is a unique type of VT that employs both bundles and the ventricular septum as integral components of a re-entrant circuit. It is usually observed in dilated cardiomyopathy, and its circuit depends exclusively on the specialized conduction system.Case presentationA 67-year-old man with a history of Fabry disease, and atrial fibrillation ablation, was admitted for a wide QRS tachycardia at 150 bpm, with an LBBB. Pharmacological therapy failed to stop the arrhythmia. Intracardiac recordings confirm the diagnosis. His Bundle recordings are essential, and Atrioventricular (AV) dissociation is typically present. The method used to induce left BBRVT is right ventricle apex stimulation. An electrophysiological study showed an AV dissociation a long HV sequence and a similar QRS morphology between VT and sinus rhythm. An overdrive stopped it. The same arrhythmia reappears and is restored to sinus rhythm by electrical cardioversion. We decided to implant an Implantable Cardiac defibrillator (ICD) with a backup pacing for secondary prevention and to ablate the right bundle branch.ConclusionBBRVT is a rare entity that is underreported. Pharmacological therapy is usually inefficient. An ICD is recommended for secondary prevention and can provide backup pacing, frequently required after catheter ablation to prevent the development of AV block or an excessive prolonged HV interval. Catheter ablation of the bundle branch is the first-line therapy.

Sinus rhythm activation signature indicates reentrant ventricular tachycardia inducibility and approximate isthmus location

BackgroundSinus rhythm activation time is useful to assess infarct border zone substrate. ObjectiveWe sought to further investigate sinus activation in ventricular tachycardia (VT). MethodsCanine postinfarction data were analyzed retrospectively. In each experiment, an infarct was created in the left ventricular wall by left anterior descending coronary artery ligation. At 3 to 5 days after ligation, 196–312 bipolar electrograms were recorded from the anterior left ventricular epicardium overlapping the infarct border zone. Sustained monomorphic VT was induced by premature electrical stimulation in 50 experiments and was noninducible in 43 experiments. Acquired sinus rhythm and VT electrograms were marked for electrical activation time, and activation maps of representative sinus rhythm and VT cycles were constructed. The sinus rhythm activation signature was defined as the cumulative number of multielectrode recording sites that had activated per time epoch, and its derivative was used to predict VT inducibility and to define the sinus rhythm slow/late activation sequence. ResultsPlotting mean activation signature derivative, a best cutoff value was useful to separate experiments with reentrant VT inducibility (sensitivity, 42/50) vs noninducibility (specificity, 39/43), with an accuracy of 81 of 93. For the 50 experiments with inducible VT, recording sites overlying a segment of isochrone encompassing the sinus rhythm slow/late activation sequence spanned the VT isthmus location in 32 cases (64%), partially spanned it in 15 cases (30%), but did not span it in 3 cases (6%). ConclusionThe sinus rhythm activation signature derivative is assistive to differentiate substrate supporting reentrant VT inducibility vs noninducibility and to identify slow/late activation for targeting isthmus location.

Transmural APD heterogeneity determines ventricular arrhythmogenesis in LQT8 syndrome: Insights from Bidomain computational modeling.

Long QT Syndrome type 8 (LQT8) is a cardiac arrhythmic disorder associated with Timothy Syndrome, stemming from mutations in the CACNA1C gene, particularly the G406R mutation. While prior studies hint at CACNA1C mutations' role in ventricular arrhythmia genesis, the mechanisms, especially in G406R presence, are not fully understood. This computational study explores how the G406R mutation, causing increased transmural dispersion of repolarization, induces and sustains reentrant ventricular arrhythmias. Using three-dimensional numerical simulations on an idealized left-ventricular model, integrating the Bidomain equations with the ten Tusscher-Panfilov ionic model, we observe that G406R mutation with 11% and 50% heterozygosis significantly increases transmural dispersion of repolarization. During S1-S4 stimulation protocols, these gradients facilitate conduction blocks, triggering reentrant ventricular tachycardia. Sustained reentry pathways occur only with G406R mutation at 50% heterozygosis, while neglecting transmural heterogeneities of action potential duration prevents stable reentry, regardless of G406R mutation presence.

Novel training concept utilizing a real world-like EP simulator

Abstract Background Training in the field of invasive cardiac electrophysiology (EP) is challenging and requires intellectual skills related to the interpretation of intracardiac electrograms. Classic approach to education of young electrophysiologists focused solely on theoretical knowledge and overseen procedures in patients as no real life like simulation of complete diagnostic and therapeutic EP studies was available. Purpose The purpose of this study was to assess a novel tool for EP training based on fully interactive, online simulator providing real clinical experience to the users. Methods EP Simulator replicates EP recording system routinely used in cardiac electrophysiology laboratories and therefore enable easier transition from training to clinical situation. Users are able to access a fully functional system with simulated surface electrocardiogram and intracardiac electrograms mimicking signals recorded by a catheter located at high right atrium, His bundle, coronary sinus, and right ventricular apex. Normal electrophysiology study and the following cardiac arrhythmias are available for simulation: sick sinus syndrome, AV conduction blocks, atrial ectopy, atrial flutter and fibrillation, atrio-ventricular and atrio-ventricular nodal reentrant tachycardia and ventricular tachycardias. Evaluation by 40 electrophysiologists (mean experience 8±6y) from 16 countries was collected via online questionnaire. Results Realism of ECG signals was described as excellent or very good by 90% of responders, realism of intracardial signals by 82.5%. Realism of signal interactions and user experience was judged as excellent or very good by 75% and 70%, respectively. 100% of users agree definitely or mostly that EP Simulator helps to translate theoretical into practical knowledge. 97.5% of responders would include it in EP training programs as it is extremely or very useful for training purposes in opinion of 87.5%. 72.5% of responders think that training on EP simulator can potentially reduce rate of complications. In 87.5% the overall experience of EP simulator was completely or mostly satisfying and it would be recommended by 100% of respondents. Conclusion EP simulator is a feasible tool for training of young electrophysiologist and it may be potentially included in cardiologist curriculum. We should particularly emphasize the positive respondents’ evaluation of EP simulator overall realism. Further systematic evaluation of the training progress is needed.

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.

Correlation relationships of the reentrant ventricular tachycardia circuit

IntroductionA quantitative analysis of the components of reentrant ventricular tachycardia (VT) circuitry could improve understanding of its onset and perpetuation. MethodIn 19 canine experiments, the left anterior descending coronary artery was ligated to generate a subepicardial infarct. The border zone resided at the epicardial surface of the anterior left ventricle and was mapped 3–5 days postinfarction with a 196–312 bipolar multielectrode array. Monomorphic VT was inducible by extrastimulation. Activation maps revealed an epicardial double-loop reentrant circuit and isthmus, causing VT. Several circuit parameters were analyzed: the coupling interval for VT induction, VT cycle length, the lateral isthmus boundary (LIB) lengths, and isthmus width and angle. ResultsThe extrastimulus interval for VT induction and the VT cycle length were strongly correlated (p < 0.001). Both the extrastimulus interval and VT cycle length were correlated to the shortest LIB (p < 0.005). A derivation was developed to suggest that when conduction block at the shorter LIB is functional, the VT cycle length may depend on the local refractory period and the delay from wavefront pivot around the LIB. Isthmus width and angle were uncorrelated to other parameters. ConclusionsThe shorter LIB is correlated to VT cycle length, hence its circuit loop may drive reentrant VT. The extrastimulation interval, VT cycle length, and shorter LIB are intertwined, and may depend upon the local refractory period. Isthmus width and angle are less correlated, perhaps being more related to electrical discontinuity caused by alterations in infarct shape at depth.

Deep learning-mediated prediction of concealed accessory pathway based on sinus rhythmic electrocardiograms.

Concealed accessory pathway (AP) may cause atrial ventricular reentrant tachycardia impacting the health of patients. However, it is asymptomatic and undetectable during sinus rhythm. To detect concealed AP with electrocardiography (ECG) images, we collected normal sinus rhythmic ECG images of concealed AP patients and healthy subjects. All ECG images were randomly allocated to the training and testing datasets, and were used to train and test six popular convolutional neural networks from ImageNet pre-training and random initialization, respectively. We screened 152 ECG recordings in concealed AP group and 600 ECG recordings in control group. There were no statistically significant differences in ECG characteristics between control group and concealed AP group in terms of PR interval and QRS interval. However, the QT interval and QTc were slightly higher in control group than in concealed AP group. In the testing set, ResNet26, SE-ResNet50, MobileNetV3_large_100, and DenseNet169 achieved a sensitivity rate more than 87.0% with a specificity rate above 98.0%. And models trained from random initialization showed similar performance and convergence with models trained from ImageNet pre-training. Our study suggests that deep learning could be an effective way to predict concealed AP with normal sinus rhythmic ECG images. And our results might encourage people to rethink the possibility of training from random initialization on ECG image tasks.

Sex Related Differences in Electrocardiography.

Since its implementation into the clinical medicine by Willem Einthoven electrocardiography had become one of crucial diagnostic method in cardiology. In spite of this fact effects of gender differences on parameters of electrocardiographic recordings started to be studied only recently. Sex related differences in physiological ECG are only minimal in childhood but there are developing during adolescence reflecting rapidly evolving differences particularly in hormonal secretion and activity of an autonomic nervous system. The heart rate is approximately 7 % higher in women than in men, PQ and QRS intervals are longer in men while QT interval is longer in women. The ST segment in females is flatter but generally the sex-related differences in ST-T waveform patterns are relatively very small with higher level of ST segment and taller T wave in men. The effects of sex-related differences, including sex hormones, on cardiac cell injury and death and their influence in determining rhythmogenesis and action potential configuration and conduction play an important role in clinics. Women have a higher prevalence of sick sinus syndrome, inappropriate sinus tachycardia, atrioventricular nodal reentry tachycardia, idiopathic right ventricular tachycardia, and arrhythmic events in the long QT syndrome. In contrast, men have a higher prevalence of atrioventricular block, carotid sinus syndrome, atrial fibrillation, supraventricular tachycardia due to accessory pathways, Wolff-Parkinson-White syndrome, reentrant ventricular tachycardia, ventricular fibrillation and sudden death, and the Brugada syndrome.

RyR2 inhibition with dantrolene is antiarrhythmic, prevents further pathological remodeling, and improves cardiac function in chronic ischemic heart disease

Diastolic Ca2+ leak due to cardiac ryanodine receptor (RyR2) hyperactivity has been widely documented in chronic ischemic heart disease (CIHD) and may contribute to ventricular tachycardia (VT) risk and progressive left-ventricular (LV) remodeling. Here we test the hypothesis that targeting RyR2 hyperactivity can suppress VT inducibility and progressive heart failure in CIHD by the RyR2 inhibitor dantrolene. Methods and resultsCIHD was induced in C57BL/6 J mice by left coronary artery ligation. Four weeks later, mice were randomized to either acute or chronic (6 weeks via implanted osmotic pump) treatment with dantrolene or vehicle. VT inducibility was assessed by programmed stimulation in vivo and in isolated hearts. Electrical substrate remodeling was assessed by optical mapping. Ca2+ sparks and spontaneous Ca2+ releases were measured in isolated cardiomyocytes. Cardiac remodeling was quantified by histology and qRT-PCR. Cardiac function and contractility were measured using echocardiography. Compared to vehicle, acute dantrolene treatment reduced VT inducibility. Optical mapping demonstrated reentrant VT prevention by dantrolene, which normalized the shortened refractory period (VERP) and prolonged action potential duration (APD), preventing APD alternans. In single CIHD cardiomyocytes, dantrolene normalized RyR2 hyperactivity and prevented spontaneous intracellular Ca2+ release. Chronic dantrolene treatment not only reduced VT inducibility but also reduced peri-infarct fibrosis and prevented further progression of LV dysfunction in CIHD mice. ConclusionsRyR2 hyperactivity plays a mechanistic role for VT risk, post-infarct remodeling, and contractile dysfunction in CIHD mice. Our data provide proof of concept for the anti-arrhythmic and anti-remodeling efficacy of dantrolene in CIHD.

Accuracy of a novel ECGi system in localising the critical isthmus exit site in scar-dependant re-entrant ventricular tachycardia

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Vision in ventricular onset (VIVO) is a novel, non-invasive, mapping system designed to locate the site of earliest activation in ventricular arrhythmia. VIVO utilises a mathematical algorithm, cross-sectional imaging data (CT or MRI), 3D images of the electrodes on the patient torso, and a 12-lead electrocardiogram (ECG) to identify the site of earliest ventricular activation.(1) The system has been shown to accurately predict earliest activation of focal premature ventricular contractions (PVCs), but its accuracy in scar dependant re-entrant ventricular tachycardia (VT) has not been investigated.(1-3) Objective To assess the accuracy of VIVO in localising the VT exit site for patients with ischaemic cardiomyopathy (ICM) and scar related re-entrant VT. Methods 5 patients with ICM (age 56 ± 19 yrs, male n = 5) were investigated (table 1). All patients had an implantable cardioverter-defibrillator with standard indications for VT ablation. Invasive electro-anatomical mapping was performed with the Advisor HD Grid multipolar catheter and maps were generated using omnipolar electrograms (EGMs). The VT exit site was identified using activation ± pace-maps and the location defined by the primary operator using the American Heart Association (AHA) 17 segment model of the left ventricle.(4) Using the intra-procedural VT ECG recordings, VIVO maps were constructed post-procedure. The VIVO predicted VT exit site was identified using the AHA 17-segment model by a second operator, blinded to the results of the procedure. A "complete match" was defined as exact segment concordance between the two operators, "partial match" as adjacent segments, and "no match" if neither requirements satisfied. Results Mean left ventricular ejection fraction was 30.5 ± 9.0%. Mean procedure time was 233 ± 31 minutes, with a mean ablation time of 24 ± 18 minutes. A total of 11 re-entrant VTs were mapped. The VT exit site was identified in all cases (10 activation-map; 1 pace-map). A complete match was seen in 91% of VTs and partial match in 9% (table 2). None of the cases demonstrated a "no match" between the invasive and VIVO maps. There were no procedural complications. Conclusion The VIVO mapping system can accurately predict the VT exit site in scar dependant re-entrant VT. Further studies to assess the feasibility of VIVO-guided ablation in scar dependant VT are ongoing.

Anatomy of the isthmus: unraveling tissue composition of ventricular tachycardia diastolic pathway

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Spanish Ministry of Science and Innovation Background 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. Purpose 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). Methods 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. Results 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 1). 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 (figure 2). Conclusion 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.

Lateral Boundaries of the Ventricular Tachycardia Circuit Align With Sinus Rhythm Discontinuities

BackgroundSinus rhythm electrical activation mapping can provide information regarding the ischemic re-entrant ventricular tachycardia (VT) circuit. The information gleaned may include the localization of sinus rhythm electrical discontinuities, which can be defined as arcs of disrupted electrical conduction with large activation time differences across the arc. ObjectivesThis study sought to detect and localize sinus rhythm electrical discontinuities that might be present in activation maps constructed from infarct border zone electrograms. MethodsMonomorphic re-entrant VT with a double-loop circuit and central isthmus was repeatedly inducible by programmed electrical stimulation in the epicardial border zone of 23 postinfarction canine hearts. Sinus rhythm and VT activation maps were constructed from 196 to 312 bipolar electrograms acquired surgically at the epicardial surface and analyzed computationally. A complete re-entrant circuit was mappable from the epicardial electrograms of VT, and isthmus lateral boundary (ILB) locations were ascertained. The difference in sinus rhythm activation time across ILB locations, vs the central isthmus and vs the circuit periphery, was determined. ResultsSinus rhythm activation time differences averaged 14.4 milliseconds across the ILB vs 6.5 milliseconds at the central isthmus and 6.4 milliseconds at the periphery (ie, the outer circuit loop) (P ≤ 0.001). Locations with large sinus rhythm activation difference tended to overlap ILB (60.3% ± 23.2%) compared with their overlap with the entire grid (27.5% ± 18.5%) (P < 0.001). ConclusionsDisrupted electrical conduction is evident as discontinuity in sinus rhythm activation maps, particularly at ILB locations. These areas may represent permanent fixtures relating to spatial differences in border zone electrical properties, caused in part by alterations in underlying infarct depth. The tissue properties producing sinus rhythm discontinuity at ILB may contribute to functional conduction block formation at VT onset.

PO-03-203 NOVEL TRAINING CONCEPT UTILIZING A REAL WORLD LIKE EP SIMULATOR

Training in the field of invasive cardiac electrophysiology (EP) is challenging and requires intellectual skills related to the interpretation of intracardiac electrograms. Classic approach to education of young electrophysiologists focused solely on theoretical knowledge and overseen procedures in patients as no real life like simulation of complete diagnostic and therapeutic EP studies was available. The purpose of this study was to assess a novel tool for EP training based on fully interactive, online simulator providing real clinical experience to the users. EP Simulator replicates EP recording system routinely used in cardiac electrophysiology laboratories and therefore enable easier transition from training to clinical situation. Users are able to access a fully functional system with simulated surface electrocardiogram and intracardiac electrograms mimicking signals recorded by a catheter located at high right atrium, His bundle, coronary sinus, and right ventricular apex. Normal electrophysiology study and the following cardiac arrhythmias are available for simulation: sick sinus syndrome, AV conduction blocks, atrial ectopy, atrial flutter and fibrillation, atrio-ventricular and atrio-ventricular nodal reentrant tachycardia and ventricular tachycardias. Evaluation by 35 electrophysiologists (mean experience 10±6y) from 14 countries was collected via online questionnaire. To every question 5 gradual answers were proposed. Realism of ECG signals was described as excellent or very good by 88% of responders, of intracardial signals by 80%. Realism of signal interactions and user experience was judged as excellent or very good by 75% and 70% accordingly. 100% of users agree definitely or mostly that EP Simulator helps to translate theoretical into practical knowledge. 97% or responders would include it in EP training programs as it is extremely or very useful for training purposes in opinion of 85%. 70% of responders think that training on EP simulator can potentially reduce rate of complications. In 85% the overall experience was completely or mostly satisfying and would be recommended by 100% of responders. Real life like EP simulator is a feasible tool for training of young electrophysiologist. Further systematic evaluation of the training progress is warranted.