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.

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.

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.

Time matters: adenosine testing immediately after pulmonary vein isolation does not substitute a waiting period.

AIMS: Adenosine testing can reveal dormant pulmonary vein (PV) conduction after PV antrum isolation (PVAI). However, the optimal timing for adenosine administration is unknown. We hypothesized that adenosine testing immediately after PVAI reliably reveals PV reconnection and thereby eliminates the need for an observation period. METHODS AND RESULTS: Fifty patients underwent PVAI. Immediately after isolation of a PV pair, adenosine was administered. Both PV pairs were separately tested. If adenosine restored PV conduction, PVs were re-isolated. During a ≥30 min observation period after immediate adenosine-guided isolation, spontaneous reconnection was assessed and reconnected PVs were re-isolated. After the observation period, adenosine testing was repeated. Immediate adenosine testing revealed dormant conduction in 10.4% of the left PVs and 16.3% of the right PVs. All PVs were successfully re-isolated. During a mean observation period of 36 ± 10 min, spontaneous reconnection occurred in 8.2% of the left and 16.3% of the right PVs. None of these PVs had shown reconnection during immediate testing. Late adenosine testing revealed dormant conduction in 12.5% of the left and 16.3% of the right PVs. In patients without reconnection during immediate adenosine testing, 14.6% of the left PVs and 30.6% of the right PVs showed either spontaneous reconnection or restored PV conduction during late adenosine testing. CONCLUSION: Adenosine testing immediately after PVAI does not reliably exclude later spontaneous or adenosine-induced PV reconnection. Adenosine testing should be performed after an appropriate observation period to reduce risk of PV reconnection.

Five-year efficacy of pulmonary vein antrum isolation as a primary ablation strategy for atrial fibrillation: a single-centre cohort study.

AIMS: Pulmonary vein antrum isolation (PVAI) is the cornerstone of atrial fibrillation (AF) ablation. There is an ongoing discussion on whether and when to add substrate modification to PVAI. This study evaluates (1) long-term efficacy of PVAI as a primary ablation strategy in all patients independently from AF type and (2) predictors of arrhythmia recurrence. METHODS AND RESULTS: A total of 509 consecutive patients (mean age 57 years, 38.9% non-paroxysmal AF) with AF underwent PVAI. In redo procedures, ablation was restricted to re-pulmonary vein (PV) isolation in case of PV reconnection. If the PVs were found to be isolated, substrate modification was performed. In total, 774 procedures were performed. Mean follow-up duration after the first and last ablation was, respectively, 66 ± 23 and 55 ± 25 months. A single PVAI was sufficient in restoring and maintaining long-term sinus rhythm in 41.3% (n = 210) of patients. Multiple procedures (mean 1.5) with re-PV isolation increased long-term success to 58.3% (n = 297). Additional substrate modification (n = 70) increased success to 62.5% (n = 318). After the last ablation, 87.5% of patients experienced success or significant clinical improvement on or off antiarrhythmic drugs. The incidence of left-sided atrial flutter or atrial tachycardia was 5% after PVAI and increased to 32% after additional substrate modification. Independent predictors for arrhythmia recurrence after the last ablation were non-paroxysmal AF, female sex, body mass index, hypertension, and AF duration. CONCLUSION: Five-year freedom of atrial tachyarrhythmia could be achieved by PVAI as primary ablation strategy in 58.3% of patients. Additional substrate modification only moderately increased overall success.

Impact of pulmonary vein antrum isolation on left atrial size and function in patients with atrial fibrillation.

PURPOSE: The success of PVAI in eliminating AF has been proven; however, its impact on the LA remains uncertain. This study aimed to determine the impact of pulmonary vein antrum isolation (PVAI) on left atrial (LA) size and function in patients with atrial fibrillation (AF). METHODS: Consecutive patients with AF were included (n = 206). Magnetic resonance imaging (MRI) was performed before and after PVAI in all patients. A subgroup (n = 52) underwent delayed enhancement MRI. Maximal LA volume (LAVmax) and minimal LA volume (LAVmin) were assessed by Simpson's rule. LA function was determined by calculating LA ejection fraction (LA EF). LA fibrosis was manually encircled and summed in the region of interest. RESULTS: Single procedure success rate was 64 %. LAVmax decreased post-ablation in all patients (125.1 to 111.9 ml, p < 0.001). LAVmin only decreased in patients with a successful outcome post-ablation (65.6 to 58.8 ml, p < 0.001). As a result, LA EF only showed a marked reduction in patients with AF recurrences (42.7 % to 37.9 %, p < 0.001). Post-ablation LA fibrosis could be visualized in 77 % of patients who underwent delayed enhancement MRI (mean amount 1.4 cm(3)). LA fibrosis showed no correlation with the decrease in LAVmax or LA EF. CONCLUSIONS: PVAI resulted in a reduction of LAVmax in all patients, indicating an effect of ablation induced fibrosis. LAVmin only decreased in patients with a successful outcome, indicating an effect of reverse atrial remodeling. As a result, LA function post-ablation was preserved in patients with a successful outcome and decreased in patients with AF recurrence.