Current practice and attitudes of stroke physicians towards rhythm-control therapy for stroke prevention: results of an international survey.

BACKGROUND: Patients with ischemic stroke and atrial fibrillation (AF) are at particularly high risk for recurrent stroke and cardiovascular events. Early rhythm control has been shown to be superior to usual care for the prevention of stroke and cardiovascular events for people with early AF. There are no data on the willingness to use rhythm control for patients with AF and acute ischemic stroke in clinical practice. METHODS: An online survey was carried out among stroke physicians to assess current practice and attitudes toward rhythm control in patients with AF and acute ischemic stroke between December 22nd 2021 and March 24th 2022. RESULTS: The survey was completed by 277 physicians including 237 from 15 known countries and 40 from unspecified countries. 79% (210/266) reported that they do not regularly apply treatment for rhythm control by ablation or antiarrhythmic drugs at all or only in small numbers (≤ 10%) of patients with AF and acute ischemic stroke. In those patients treated with rhythm-control therapy, antiarrhythmic drugs were used by the majority of respondents (89%), while only a minority reported using AF ablation (11%). 88% of respondents (221/250) stated that they would be willing to randomize patients with AF after acute ischemic stroke to either early rhythm control or usual care in a clinical trial. CONCLUSION: Despite its potential benefit, few patients with AF and acute ischemic stroke appear to be treated with rhythm control, which may result from uncertainty regarding potential complications of antiarrhythmic therapy in patients with acute stroke. Together with recent data on the effectiveness of early rhythm control in patients with a history of stroke, these results call for a randomized clinical trial to assess the efficacy of early rhythm control in patients with acute ischemic stroke and AF.

Body surface potential mapping detects early disease onset in plakophilin-2-pathogenic variant carriers.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive inherited cardiac disease. Early detection of disease and risk stratification remain challenging due to heterogeneous phenotypic expression. The standard configuration of the 12 lead electrocardiogram (ECG) might be insensitive to identify subtle ECG abnormalities. We hypothesized that body surface potential mapping (BSPM) may be more sensitive to detect subtle ECG abnormalities. METHODS AND RESULTS: We obtained 67 electrode BSPM in plakophilin-2 (PKP2)-pathogenic variant carriers and control subjects. Subject-specific computed tomography/magnetic resonance imaging based models of the heart/torso and electrode positions were created. Cardiac activation and recovery patterns were visualized with QRS- and STT-isopotential map series on subject-specific geometries to relate QRS-/STT-patterns to cardiac anatomy and electrode positions. To detect early signs of functional/structural heart disease, we also obtained right ventricular (RV) echocardiographic deformation imaging. Body surface potential mapping was obtained in 25 controls and 42 PKP2-pathogenic variant carriers. We identified five distinct abnormal QRS-patterns and four distinct abnormal STT-patterns in the isopotential map series of 31/42 variant carriers. Of these 31 variant carriers, 17 showed no depolarization or repolarization abnormalities in the 12 lead ECG. Of the 19 pre-clinical variant carriers, 12 had normal RV-deformation patterns, while 7/12 showed abnormal QRS- and/or STT-patterns. CONCLUSION: Assessing depolarization and repolarization by BSPM may help in the quest for early detection of disease in variant carriers since abnormal QRS- and/or STT-patterns were found in variant carriers with a normal 12 lead ECG. Because electrical abnormalities were observed in subjects with normal RV-deformation patterns, we hypothesize that electrical abnormalities develop prior to functional/structural abnormalities in ARVC.

ECG-based techniques to enhance clinical practice in cardiac genetic disease management.

INTRODUCTION: Inherited cardiomyopathies are associated with a broad spectrum of potentially lethal phenotypes characterized by structural and electrical myocardial remodeling. Increased awareness and genetic cascade screening lead to more genotype-positive, yet phenotype-negative individuals to be evaluated and followed up. The predictive value of genetic testing is hampered by incomplete penetrance and high variability in disease onset, progression and severity. CLINICAL CHALLENGES: Dilated cardiomyopathy usually manifests with symptoms of heart failure and ventricular arrhythmias (VA) develop in advanced disease. In arrhythmogenic cardiomyopathy (ACM), electrical remodeling can precede structural and functional changes and life-threatening VA can be the first disease manifestation. Early signs and symptoms may be subtle and go unnoticed. Physicians are in great need of appropriate screening and risk-stratification strategies. Task Force Criteria (TFC) were established to standardize the clinical diagnosis of ACM but risk-stratification remains challenging. Accurate prediction of disease progression in variation carriers is currently beyond the capabilities of diagnostic tests. PROPOSED DIAGNOSTIC TECHNIQUES: We propose three ECG-based techniques; isopotential mapping, inverse ECG and CineECG, to enhance risk-stratification in ACM. With the use of isopotential mapping abnormal spatio-temporal activation and repolarization may be identified. Furthermore, by combining subject specific ≥12­lead ECG data with cardiothoracic imaging using inverse ECG techniques, the direct link between ECG and cardiac anatomy can be obtained. CONCLUSION: New ECG techniques may prove more sensitive to detect early de- and repolarization abnormalities in yet asymptomatic variation carriers. Early electrical signs of disease progression may be identified prior to symptoms. Furthermore, individualized risk-stratification may be enhanced.

Feasibility of Linear Irreversible Electroporation Ablation in the Coronary Sinus.

INTRODUCTION: Previous studies demonstrated that the coronary sinus (CS) is an important target for ablation in persistent atrial fibrillation. However, radiofrequency ablation in the CS is associated with coronary vessel damage and tamponade. Animal data suggest irreversible electroporation (IRE) ablation can be a safe ablation modality in vicinity of coronary arteries. We investigated the feasibility of IRE in the CS in a porcine model. METHODS: Ablation and pacing was performed in the CS in six pigs (weight 60-75 kg) using a modified 9-French steerable linear hexapolar Tip-Versatile Ablation Catheter. Pacing maneuvers were performed from distal to proximal segments of the CS to assess atrial capture thresholds before and after IRE application. IRE ablations were performed with 100 J IRE pulses. After 3-week survival animals were euthanized and histological sections from the CS were analyzed. RESULTS: A total of 27 IRE applications in six animals were performed. Mean peak voltage was 1509 ± 36 V, with a mean peak current of 22.9 ± 1.0 A. No complications occurred during procedure and 3-week survival. At 30 min post ablation 100% isolation was achieved in all animals. At 3 weeks follow-up pacing thresholds were significant higher as compared to baseline. Histological analysis showed transmural ablation lesions in muscular sleeves surrounding the CS. CONCLUSION: IRE ablation of the musculature along the CS using a multi-electrode catheter is feasible in a porcine model.

Multielectrode Contact Measurement Can Improve Long-Term Outcome of Pulmonary Vein Isolation Using Circular Single-Pulse Electroporation Ablation.

BACKGROUND: Irreversible electroporation (IRE) ablation is generally performed with multielectrode catheters. Electrode-tissue contact is an important predictor for the success of pulmonary vein (PV) isolation; however, contact force is difficult to measure with multielectrode ablation catheters. In a preclinical study, we assessed the feasibility of a multielectrode impedance system (MEIS) as a predictor of long-term success of PV isolation. In addition, we present the first-in-human clinical experience with MEIS. METHODS: In 10 pigs, one PV was ablated based on impedance (MEIS group), and the other PV was solely based on local electrogram information (EP group). IRE ablations were performed at 200 J. After 3 months, recurrence of conduction was assessed. Subsequently, in 30 patients undergoing PV isolation with IRE, MEIS was evaluated and MEIS contact values were compared to local electrograms. RESULTS: In the porcine study, 43 IRE applications were delivered in 19 PVs. Acutely, no reconnections were observed in either group. After 3 months, 0 versus 3 (P=0.21) PVs showed conduction recurrence in the MEIS and EP groups, respectively. Results from the clinical study showed a significant linear relation was found between mean MEIS value and bipolar dV/dt (r2=0.49, P<0.001), with a slope of 20.6 mV/s per Ohm. CONCLUSIONS: Data from the animal study suggest that MEIS values predict effective IRE applications. For the long-term success of electrical PV isolation with circular IRE applications, no significant difference in efficacy was found between ablation based on the measurement of electrode interface impedance and ablation using the classical EP approach for determining electrode-tissue contact. Experiences of the first clinical use of MEIS were promising and serve as an important basis for future research.

Life-threatening ventricular arrhythmia prediction in patients with dilated cardiomyopathy using explainable electrocardiogram-based deep neural networks.

AIMS: While electrocardiogram (ECG) characteristics have been associated with life-threatening ventricular arrhythmias (LTVA) in dilated cardiomyopathy (DCM), they typically rely on human-derived parameters. Deep neural networks (DNNs) can discover complex ECG patterns, but the interpretation is hampered by their 'black-box' characteristics. We aimed to detect DCM patients at risk of LTVA using an inherently explainable DNN. METHODS AND RESULTS: In this two-phase study, we first developed a variational autoencoder DNN on more than 1 million 12-lead median beat ECGs, compressing the ECG into 21 different factors (F): FactorECG. Next, we used two cohorts with a combined total of 695 DCM patients and entered these factors in a Cox regression for the composite LTVA outcome, which was defined as sudden cardiac arrest, spontaneous sustained ventricular tachycardia, or implantable cardioverter-defibrillator treated ventricular arrhythmia. Most patients were male (n = 442, 64%) with a median age of 54 years [interquartile range (IQR) 44-62], and median left ventricular ejection fraction of 30% (IQR 23-39). A total of 115 patients (16.5%) reached the study outcome. Factors F8 (prolonged PR-interval and P-wave duration, P < 0.005), F15 (reduced P-wave height, P = 0.04), F25 (increased right bundle branch delay, P = 0.02), F27 (P-wave axis P < 0.005), and F32 (reduced QRS-T voltages P = 0.03) were significantly associated with LTVA. CONCLUSION: Inherently explainable DNNs can detect patients at risk of LTVA which is mainly driven by P-wave abnormalities.

Modeling the His-Purkinje Effect in Non-invasive Estimation of Endocardial and Epicardial Ventricular Activation.

Inverse electrocardiography (iECG) estimates epi- and endocardial electrical activity from body surface potentials maps (BSPM). In individuals at risk for cardiomyopathy, non-invasive estimation of normal ventricular activation may provide valuable information to aid risk stratification to prevent sudden cardiac death. However, multiple simultaneous activation wavefronts initiated by the His-Purkinje system, severely complicate iECG. To improve the estimation of normal ventricular activation, the iECG method should accurately mimic the effect of the His-Purkinje system, which is not taken into account in the previously published multi-focal iECG. Therefore, we introduce the novel multi-wave iECG method and report on its performance. Multi-wave iECG and multi-focal iECG were tested in four patients undergoing invasive electro-anatomical mapping during normal ventricular activation. In each subject, 67-electrode BSPM were recorded and used as input for both iECG methods. The iECG and invasive local activation timing (LAT) maps were compared. Median epicardial inter-map correlation coefficient (CC) between invasive LAT maps and estimated multi-wave iECG versus multi-focal iECG was 0.61 versus 0.31. Endocardial inter-map CC was 0.54 respectively 0.22. Modeling the His-Purkinje system resulted in a physiologically realistic and robust non-invasive estimation of normal ventricular activation, which might enable the early detection of cardiac disease during normal sinus rhythm.

CineECG: A novel method to image the average activation sequence in the heart from the 12-lead ECG.

The standard 12-lead electrocardiogram (ECG) is a diagnostic tool to asses cardiac electrical activity. The vectorcardiogram is a related tool that represents that activity as the direction of a vector. In this work we investigate CineECG, a new 12-lead ECG based analysis method designed to directly estimate the average cardiac anatomical location of activation over time. We describe CineECG calculation and a novel comparison parameter, the average isochrone position (AIP). In a model study, fourteen different activation sequences were simulated and corresponding 12-lead ECGs were computed. The CineECG was compared to AIP in terms of location and direction. In addition, 67-lead body surface potential maps from ten patients were used to study the sensitivity of CineECG to electrode mispositioning and anatomical model selection. Epicardial activation maps from four patients were used for further evaluation. The average distance between CineECG and AIP across the fourteen sequences was 23.7 ± 2.4 mm, with significantly better agreement in the terminal (27.3 ± 5.7 mm) versus the initial QRS segment (34.2 ± 6.1 mm). Up to four cm variation in electrode positioning produced an average distance of 6.5 ± 4.5 mm between CineECG trajectories, while substituting a generic heart/torso model for a patient-specific one produced an average difference of 6.1 ± 4.8 mm. Dominant epicardial activation map features were recovered. Qualitatively, CineECG captured significant features of activation sequences and was robust to electrode misplacement. CineECG provides a realistic representation of the average cardiac activation in normal and diseased hearts. In particular, the terminal segment of the CineECG might be useful to detect pathology.

Incorporating structural abnormalities in equivalent dipole layer based ECG simulations.

Introduction: Electrical activity of the myocardium is recorded with the 12-lead ECG. ECG simulations can improve our understanding of the relation between abnormal ventricular activation in diseased myocardium and body surface potentials (BSP). However, in equivalent dipole layer (EDL)-based ECG simulations, the presence of diseased myocardium breaks the equivalence of the dipole layer. To simulate diseased myocardium, patches with altered electrophysiological characteristics were incorporated within the model. The relation between diseased myocardium and corresponding BSP was investigated in a simulation study. Methods: Activation sequences in normal and diseased myocardium were simulated and corresponding 64-lead BSP were computed in four models with distinct patch locations. QRS-complexes were compared using correlation coefficient (CC). The effect of different types of patch activation was assessed. Of one patient, simulated electrograms were compared to electrograms recorded during invasive electro-anatomical mapping. Results: Hundred-fifty-three abnormal activation sequences were simulated. Median QRS-CC of delayed versus dyssynchronous were significantly different (1.00 vs. 0.97, p < 0.001). Depending on the location of the patch, BSP leads were affected differently. Within diseased regions, fragmentation, low bipolar voltages and late potentials were observed in both recorded and simulated electrograms. Discussion: A novel method to simulate cardiomyopathy in EDL-based ECG simulations was established and evaluated. The new patch-based approach created a realistic relation between ECG waveforms and underlying activation sequences. Findings in the simulated cases were in agreement with clinical observations. With this method, our understanding of disease progression in cardiomyopathies may be further improved and used in advanced inverse ECG procedures.

Comparing Non-invasive Inverse Electrocardiography With Invasive Endocardial and Epicardial Electroanatomical Mapping During Sinus Rhythm.

This study presents a novel non-invasive equivalent dipole layer (EDL) based inverse electrocardiography (iECG) technique which estimates both endocardial and epicardial ventricular activation sequences. We aimed to quantitatively compare our iECG approach with invasive electro-anatomical mapping (EAM) during sinus rhythm with the objective of enabling functional substrate imaging and sudden cardiac death risk stratification in patients with cardiomyopathy. Thirteen patients (77% males, 48 ± 20 years old) referred for endocardial and epicardial EAM underwent 67-electrode body surface potential mapping and CT imaging. The EDL-based iECG approach was improved by mimicking the effects of the His-Purkinje system on ventricular activation. EAM local activation timing (LAT) maps were compared with iECG-LAT maps using absolute differences and Pearson's correlation coefficient, reported as mean ± standard deviation [95% confidence interval]. The correlation coefficient between iECG-LAT maps and EAM was 0.54 ± 0.19 [0.49-0.59] for epicardial activation, 0.50 ± 0.27 [0.41-0.58] for right ventricular endocardial activation and 0.44 ± 0.29 [0.32-0.56] for left ventricular endocardial activation. The absolute difference in timing between iECG maps and EAM was 17.4 ± 7.2 ms for epicardial maps, 19.5 ± 7.7 ms for right ventricular endocardial maps, 27.9 ± 8.7 ms for left ventricular endocardial maps. The absolute distance between right ventricular endocardial breakthrough sites was 30 ± 16 mm and 31 ± 17 mm for the left ventricle. The absolute distance for latest epicardial activation was median 12.8 [IQR: 2.9-29.3] mm. This first in-human quantitative comparison of iECG and invasive LAT-maps on both the endocardial and epicardial surface during sinus rhythm showed improved agreement, although with considerable absolute difference and moderate correlation coefficient. Non-invasive iECG requires further refinements to facilitate clinical implementation and risk stratification.

The relation of 12 lead ECG to the cardiac anatomy: The normal CineECG.

BACKGROUND: The interpretation of the 12­lead ECG is notoriously difficult and requires experts to distinguish normal from abnormal ECG waveforms. ECG waveforms depend on body build and electrode positions, both often different in males and females. To relate the ECG waveforms to cardiac anatomical structures is even more difficult. The novel CineECG algorithm enables a direct projection of the 12­lead ECG to the cardiac anatomy by computing the mean location of cardiac activity over time. The aim of this study is to investigate the cardiac locations of the CineECG derived from standard 12­lead ECGs of normal subjects. METHODS: In this study we used 6525 12­lead ECG tracings labelled as normal obtained from the certified Physionet PTB XL Diagnostic ECG Database to construct the CineECG. All 12 lead ECGs were analyzed, and then divided by age groups (18-29,30-39,40-49,50-59,60-69,70-100 years) and by gender (male/female). For each ECG, we computed the CineECG within a generic 3D heart/torso model. Based on these CineECG's, the average normal cardiac location and direction for QRS, STpeak, and TpeakTend segments were determined. RESULTS: The CineECG direction for the QRS segment showed large variation towards the left free wall, whereas the STT segments were homogeneously directed towards the septal/apical region. The differences in the CineECG location for the QRS, STpeak, and TpeakTend between the age and gender groups were relatively small (maximally 10 mm at end T-wave), although between the gender groups minor differences were found in the 4 chamber direction angles (QRS 4°, STpeak 5°, and TpeakTend 8°) and LAO (QRS 1°, STpeak 13°, and TpeakTend 30°). CONCLUSION: CineECG demonstrated to be a feasible and pragmatic solution for ECG waveform interpretation, relating the ECG directly to the cardiac anatomy. The variations in depolarization and repolarization CineECG were small within this group of normal healthy controls, both in cardiac location as well as in direction. CineECG may enable an easier discrimination between normal and abnormal QRS and T-wave morphologies, reducing the amount of expert training. Further studies are needed to prove whether novel CineECG can significantly contribute to the discrimination of normal versus abnormal ECG tracings.

Feasibility study of a 3D camera to reduce electrode repositioning errors during longitudinal ECG acquisition.

INTRODUCTION: Longitudinal monitoring of sometimes subtle waveform changes of the 12­lead electrocardiogram (ECG) is complicated by patient-specific and technical factors, such as the inaccuracy of electrode repositioning. This feasibility study uses a 3D camera to reduce electrode repositioning errors, reduce ECG waveform variability and enable detailed longitudinal ECG monitoring. METHODS: Per subject, three clinical ECGs were obtained during routine clinical follow-up. Additionally, two ECGs were recorded guided by two 3D cameras, which were used to capture the precordial electrode locations and direct electrode repositioning. ECG waveforms and parameters were quantitatively compared between 3D camera guided ECGs and clinical ECGs. Euclidian distances between original and repositioned precordial electrodes from 3D guided ECGs were measured. RESULTS: Twenty subjects (mean age 65.1 ± 8.2 years, 35% females) were included. The ECG waveform variation between routine ECGs was significantly higher compared to 3D guided ECGs, for both the QRS complex (correlation coefficient = 0.90 vs 0.98, p < 0.001) and the STT segment (correlation coefficient = 0.88 vs. 0.96, p < 0.001). QTc interval variation was reduced for 3D camera guided ECGs compared to routine clinical ECGs (5.6 ms vs. 9.6 ms, p = 0.030). The median distance between 3D guided repositioned electrodes was 10.0 [6.4-15.2] mm, and did differ between males and females (p = 0.076). CONCLUSIONS: 3D guided repositioning of precordial electrodes resulted in, a low repositioning error, higher agreement between waveforms of consecutive ECGs and a reduction of QTc variation. These findings suggest that longitudinal monitoring of disease progression using 12­lead ECG waveforms is feasible in clinical practice.

Novel CineECG enables anatomical 3D localization and classification of bundle branch blocks.

AIMS: Ventricular conduction disorders can induce arrhythmias and impair cardiac function. Bundle branch blocks (BBBs) are diagnosed by 12-lead electrocardiogram (ECG), but discrimination between BBBs and normal tracings can be challenging. CineECG computes the temporo-spatial trajectory of activation waveforms in a 3D heart model from 12-lead ECGs. Recently, in Brugada patients, CineECG has localized the terminal components of ventricular depolarization to right ventricle outflow tract (RVOT), coincident with arrhythmogenic substrate localization detected by epicardial electro-anatomical maps. This abnormality was not found in normal or right BBB (RBBB) patients. This study aimed at exploring whether CineECG can improve the discrimination between left BBB (LBBB)/RBBB, and incomplete RBBB (iRBBB). METHODS AND RESULTS: We utilized 500 12-lead ECGs from the online Physionet-XL-PTB-Diagnostic ECG Database with a certified ECG diagnosis. The mean temporo-spatial isochrone trajectory was calculated and projected into the anatomical 3D heart model. We established five CineECG classes: 'Normal', 'iRBBB', 'RBBB', 'LBBB', and 'Undetermined', to which each tracing was allocated. We determined the accuracy of CineECG classification with the gold standard diagnosis. A total of 391 ECGs were analysed (9 ECGs were excluded for noise) and 240/266 were correctly classified as 'normal', 14/17 as 'iRBBB', 55/55 as 'RBBB', 51/51 as 'LBBB', and 31 as 'undetermined'. The terminal mean temporal spatial isochrone contained most information about the BBB localization. CONCLUSION: CineECG provided the anatomical localization of different BBBs and accurately differentiated between normal, LBBB and RBBB, and iRBBB. CineECG may aid clinical diagnostic work-up, potentially contributing to the difficult discrimination between normal, iRBBB, and Brugada patients.

Follow-up after hemodynamically not tolerated ventricular tachycardia in patients with midrange reduced to normal ejection fraction: A retrospective single-centre case series.

INTRODUCTION: The benefit of implantable cardioverter-defibrillator (ICD) implantation in patients with hemodynamically not tolerated ventricular tachycardia (VT) and midrange reduced to normal ejection fraction (LVEF >35%) is currently unclear. The purpose of this study was to investigate follow-up after hemodynamically not tolerated VT in patients with LVEF >35%. In addition, we aimed to find possible predictive factors to identify who will benefit from ICD implantation. METHODS: In a retrospective single-centre case series, all patients with hemodynamically not tolerated VT and LVEF >35% that underwent electrophysiological study (EPS) and/or radiofrequency VT ablation were included. RESULTS: Forty-two patients (5 women, median age 68 years) with hemodynamically not tolerated VT and LVEF >35% underwent EPS. VT ablation was performed in thirty-one patients, which was considered successful in twenty-three patients. Nineteen patients had an ICD at discharge while 23 patients were discharged without an ICD. The severity of hemodynamic compromise, LVEF and ablation success played an important role in the decision-making for ICD implantation. Six patients (14.3%) had recurrence of VT, all hemodynamically tolerated. CONCLUSIONS: In this small case series, patients with hemodynamically not tolerated VT and LVEF >35% had a relatively low recurrence rate and all recurrences were nonfatal. Based on our results, we hypothesize that the severity of hemodynamic compromise, LVEF and ablation success might modify the risk for VA recurrence. A prospective study to determine the prognostic value of these factors in patients with hemodynamically not tolerated VT and LVEF >35% is necessary.

In vivo analysis of the origin and characteristics of gaseous microemboli during catheter-mediated irreversible electroporation.

AIMS: Irreversible electroporation (IRE) ablation is a non-thermal ablation method based on the application of direct current between a multi-electrode catheter and skin electrode. The delivery of current through blood leads to electrolysis. Some studies suggest that gaseous (micro)emboli might be associated with myocardial damage and/or (a)symptomatic cerebral ischaemic events. The aim of this study was to compare the amount of gas generated during IRE ablation and during radiofrequency (RF) ablation. METHODS AND RESULTS: In six 60-75 kg pigs, an extracorporeal femoral shunt was outfitted with a bubble-counter to detect the size and total volume of gas bubbles. Anodal and cathodal 200 J IRE applications were delivered in the left atrium (LA) using a 14-electrode circular catheter. The 30 and 60 s 40 W RF point-by-point ablations were performed. Using transoesophageal echocardiography (TOE), gas formation was visualized. Average gas volumes were 0.6 ± 0.6 and 56.9 ± 19.1 µL (P < 0.01) for each anodal and cathodal IRE application, respectively. Also, qualitative TOE imaging showed significantly less LA bubble contrast with anodal than with cathodal applications. Radiofrequency ablations produced 1.7 ± 2.9 and 6.7 ± 7.4 µL of gas, for 30 and 60 s ablation time, respectively. CONCLUSION: Anodal IRE applications result in significantly less gas formation than both cathodal IRE applications and RF applications. This finding is supported by TOE observations.

Efficacy of multi-electrode linear irreversible electroporation.

AIMS: We investigated the efficacy of linear multi-electrode irreversible electroporation (IRE) ablation in a porcine model. METHODS AND RESULTS: The study was performed in six pigs (weight 60-75 kg). After median sternotomy and opening of the pericardium, a pericardial cradle was formed and filled with blood. A linear seven polar 7-Fr electrode catheter with 2.5 mm electrodes and 2.5 mm inter-electrode spacing was placed in good contact with epicardial tissue. A single IRE application was delivered using 50 J at one site and 100 J at two other sites, in random sequence, using a standard monophasic defibrillator connected to all seven electrodes connected in parallel. The pericardium and thorax were closed and after 3 weeks survival animals were euthanized. A total of 82 histological sections from all 18 electroporation lesions were analysed. A total of seven 50 J and fourteen 100 J epicardial IRE applications were performed. Mean peak voltages at 50 and 100 J were 1079.2 V ± 81.1 and 1609.5 V ± 56.8, with a mean peak current of 15.4 A ± 2.3 and 20.2 A ± 1.7, respectively. Median depth of the 50 and 100 J lesions were 3.2 mm [interquartile range (IQR) 3.1-3.6] and 5.5 mm (IQR 4.6-6.6) (P < 0.001), respectively. Median lesion width of the 50 and 100 J lesions was 3.9 mm (IQR 3.7-4.8) and 5.4 mm (IQR 5.0-6.3), respectively (P < 0.001). Longitudinal sections showed continuous lesions for 100 J applications. CONCLUSION: Epicardial multi-electrode linear application of IRE pulses is effective in creating continuous deep lesions.

Pulmonary Vein Isolation With Single Pulse Irreversible Electroporation: A First in Human Study in 10 Patients With Atrial Fibrillation.

BACKGROUND: Irreversible electroporation (IRE) is a promising new nonthermal ablation technology for pulmonary vein (PV) isolation in patients with atrial fibrillation. Experimental data suggest that IRE ablation produces large enough lesions without the risk of PV stenosis, artery, nerve, or esophageal damage. This study aimed to investigate the feasibility and safety of single pulse IRE PV isolation in patients with atrial fibrillation. METHODS: Ten patients with symptomatic paroxysmal or persistent atrial fibrillation underwent single pulse IRE PV isolation under general anesthesia. Three-dimensional reconstruction and electroanatomical voltage mapping (EnSite Precision, Abbott) of left atrium and PVs were performed using a conventional circular mapping catheter. PV isolation was performed by delivering nonarcing, nonbarotraumatic 6 ms, 200 J direct current IRE applications via a custom nondeflectable 14-polar circular IRE ablation catheter with a variable hoop diameter (16-27 mm). A deflectable sheath (Agilis, Abbott) was used to maneuver the ablation catheter. A minimum of 2 IRE applications with slightly different catheter positions were delivered per vein to achieve circular tissue contact, even if PV potentials were abolished after the first application. Bidirectional PV isolation was confirmed with the circular mapping catheter and a post ablation voltage map. After a 30-minute waiting period, adenosine testing (30 mg) was used to reveal dormant PV conduction. RESULTS: All 40 PVs could be successfully isolated with a mean of 2.4±0.4 IRE applications per PV. Mean delivered peak voltage and peak current were 2154±59 V and 33.9±1.6 A, respectively. No PV reconnections occurred during the waiting period and adenosine testing. No periprocedural complications were observed. CONCLUSIONS: In the 10 patients of this first-in-human study, acute bidirectional electrical PV isolation could be achieved safely by single pulse IRE ablation.

Quantitative Approach to Fragmented QRS in Arrhythmogenic Cardiomyopathy: From Disease towards Asymptomatic Carriers of Pathogenic Variants.

Fragmented QRS complexes (fQRS) are common in patients with arrhythmogenic cardiomyopathy (ACM). A new method of fQRS quantification may aid early disease detection in pathogenic variant carriers and assessment of prognosis in patients with early stage ACM. Patients with definite ACM (n = 221, 66%), carriers of a pathogenic ACM-associated variant without a definite ACM diagnosis (n = 57, 17%) and control subjects (n = 58, 17%) were included. Quantitative fQRS (Q-fQRS) was defined as the total amount of deflections in the QRS complex in all 12 electrocardiography (ECG) leads. Q-fQRS was scored by a single observer and reproducibility was determined by three independent observers. Q-fQRS count was feasible with acceptable intra- and inter-observer agreement. Q-fQRS count is significantly higher in patients with definite ACM (54 ± 15) and pathogenic variant carriers (55 ± 10) compared to controls (35 ± 5) (p < 0.001). In patients with ACM, Q-fQRS was not associated with sustained ventricular arrhythmia (p = 0.701) at baseline or during follow-up (p = 0.335). Both definite ACM patients and pathogenic variant carriers not fulfilling ACM diagnosis have a higher Q-fQRS than controls. This may indicate that increased Q-fQRS is an early sign of disease penetrance. In concealed and early stages of ACM the role of Q-fQRS for risk stratification is limited.

MRI-guided pulmonary vein isolation for atrial fibrillation: what is good enough? An early health technology assessment.

Next to anticoagulation, pulmonary vein isolation (PVI) is the most important interventional procedure in the treatment of atrial fibrillation (AF). Despite widespread clinical application of this therapy, patients often require multiple procedures to reach clinical success. In contrast to conventional imaging modalities, MRI allows direct visualisation of the ablation lesion. Therefore, the use of real-time MRI to guide cardiac electrophysiology procedures may increase clinical effectiveness. An essential aspect, from a decision-making point of view, is the effect on costs and the potential cost-effectiveness of new technologies. Generally, health technology assessment (HTA) studies are performed when innovations are close to clinical application. However, early stage HTA can inform users, researchers and funders about the ultimate clinical and economic potential of a future innovation. Ultimately, this can guide funding allocation. In this study, we performed an early HTA evaluate MRI-guided PVIs. Methods: We performed an economic evaluation using a decision tree with a time-horizon of 1 year. We calculated the clinical effectiveness (defined as the proportion of patients that is long-term free of AF after a single procedure) required for MRI-guided PVI to be cost-effective compared with conventional treatment. Results: Depending on the cost-effectiveness threshold (willingness to pay for one additional quality-of-life adjusted life year (QALY), interventional MRI (iMRI) guidance for PVI can be cost-effective if clinical effectiveness is 69.8% (at €80 000/QALY) and 77.1% (at €20 000/QALY), compared with 64% for fluoroscopy-guided procedures. Conclusion: Using an early HTA, we established a clinical effectiveness threshold for interventional MRI-guided PVIs that can inform a clinical implementation strategy. If crucial technologies are developed, it seems plausible that iMRI-guided PVIs will be able to reach this threshold.

Incidence and predictors of implantable cardioverter-defibrillator therapy and its complications in idiopathic ventricular fibrillation patients.

AIMS: Idiopathic ventricular fibrillation (IVF) is a rare cause of sudden cardiac arrest. Implantable cardioverter-defibrillator (ICD) implantation is currently the only treatment option. Limited data are available on the prevalence and complications of ICD therapy in these patients. We sought to investigate ICD therapy and its complications in patients with IVF. METHODS AND RESULTS: Patients were selected from a national registry of IVF patients. Patients in whom no underlying diagnosis was found during follow-up were eligible for inclusion. Recurrence of ventricular arrhythmia (VA) was derived from medical and ICD records, electrogram records of ICD therapies were used to differentiate between appropriate or inappropriate interventions. Independent predictors for appropriate ICD shock were calculated using cox regression. In 217 IVF patients, recurrence of sustained VAs occurred in 66 patients (30%) during a median follow-up period of 6.1 years. Ten patients died (4.6%). Thirty-eight patients (17.5%) experienced inappropriate ICD therapy, and 32 patients (14.7%) had device-related complications. Symptoms before cardiac arrest [hazard ratio (HR): 2.51, 95% confidence interval (CI): 1.48-4.24], signs of conduction disease (HR: 2.27, 95% CI: 1.15-4.47), and carrier of the DPP6 risk haplotype (HR: 3.24, 1.70-6.17) were identified as independent predictors of appropriate shock occurrence. CONCLUSION: Implantable cardioverter-defibrillator therapy is an effective treatment in IVF, treating recurrences of potentially lethal VAs in approximately one-third of patients during long-term follow-up. However, device-related complications and inappropriate shocks were also frequent. We found significant predictors for appropriate ICD therapy. This may imply that these patients require additional management to prevent recurrent events.