Non-invasive three-dimensional electrical activation mapping to predict cardiac resynchronization therapy response: site of latest left ventricular activation relative to pacing site.

AIMS: Pacing remote from the latest electrically activated site (LEAS) in the left ventricle (LV) may diminish response to cardiac resynchronization therapy (CRT). We tested whether proximity of LV pacing site (LVPS) to LEAS, determined by non-invasive three-dimensional electrical activation mapping [electrocardiographic Imaging (ECGI)], increased likelihood of CRT response. METHODS AND RESULTS: Consecutive CRT patients underwent ECGI and chest/heart computed tomography 6-24 months of post-implant. Latest electrically activated site and the distance to LVPS (dp) were assessed. Left ventricular end-systolic volume (LVESV) reduction of ≥15% at clinical follow-up defined response. Logistic regression probabilistically modelled non-response; variables included demographics, heart failure classification, left bundle branch block (LBBB), ischaemic heart disease (IHD), atrial fibrillation, QRS duration, baseline ejection fraction (EF) and LVESV, comorbidities, use of CRT optimization algorithm, angiotensin-converting enzyme inhibitor(ACE)/angiotensin-receptor blocker (ARB), beta-blocker, diuretics, and dp. Of 111 studied patients [64 ± 11 years, EF 28 ± 6%, implant duration 12 ± 5 months (mean ± SD), 98% had LBBB, 38% IHD], 67% responded at 10 ± 3 months post CRT-implant. Latest electrically activated sites were outside the mid-to-basal lateral segments in 35% of the patients. dp was 42 ± 23 mm [31 ± 14 mm for responders vs. 63 ± 24 mm non-responders (P < 0.001)]. Longer dp and the lack of use of CRT optimization algorithm were the only independent predictors of non-response [area under the curve (AUC) 0.906]. dp of 47 mm delineated responders and non-responders (AUC 0.931). CONCLUSION: The distance between LV pacing site and latest electrical activation is a strong independent predictor for CRT response. Non-invasive electrical evaluation to characterize intrinsic activation and guide LV lead deployment may improve CRT efficacy.

Parameter variations in personalized electrophysiological models of human heart ventricles.

The objectives of this study were to evaluate the accuracy of personalized numerical simulations of the electrical activity in human ventricles by comparing simulated electrocardiograms (ECGs) with real patients' ECGs and analyzing the sensitivity of the model output to variations in the model parameters. We used standard 12-lead ECGs and up to 224 unipolar body-surface ECGs to record three patients with cardiac resynchronization therapy devices and three patients with focal ventricular tachycardia. Patient-tailored geometrical models of the ventricles, atria, large vessels, liver, and spine were created using computed tomography data. Ten cases of focal ventricular activation were simulated using the bidomain model and the TNNP 2006 cellular model. The population-based values of electrical conductivities and other model parameters were used for accuracy analysis, and their variations were used for sensitivity analysis. The mean correlation coefficient between the simulated and real ECGs varied significantly (from r = 0.29 to r = 0.86) among the simulated cases. A strong mean correlation (r > 0.7) was found in eight of the ten model cases. The accuracy of the ECG simulation varied widely in the same patient depending on the localization of the excitation origin. The sensitivity analysis revealed that variations in the anisotropy ratio, blood conductivity, and cellular apicobasal heterogeneity had the strongest influence on transmembrane potential, while variation in lung conductivity had the greatest influence on body-surface ECGs. Futhermore, the anisotropy ratio predominantly affected the latest activation time and repolarization time dispersion, while the cellular apicobasal heterogeneity mainly affected the dispersion of action potential duration, and variation in lung conductivity mainly led to changes in the amplitudes of ECGs and cardiac electrograms. We also found that the effects of certain parameter variations had specific regional patterns on the cardiac and body surfaces. These observations are useful for further developing personalized cardiac models.

Solving the Inverse Problem of Electrocardiography on the Endocardium Using a Single Layer Source.

The inverse problem of electrocardiography consists in reconstructing cardiac electrical activity from given body surface electrocardiographic measurements. Despite tremendous progress in the field over the last decades, the solution of this problem in terms of electrical potentials on both epi- and the endocardial heart surfaces with acceptable accuracy remains challenging. This paper presents a novel numerical approach aimed at improving the solution quality on the endocardium. Our method exploits the solution representation in the form of electrical single layer densities on the myocardial surface. We demonstrate that this representation brings twofold benefits: first, the inverse problem can be solved for the physiologically meaningful single layer densities. Secondly, a conventional transfer matrix for electrical potentials can be split into two parts, one of which turned out to posess regularizing properties leading to improved endocardial reconstructions. The method was tested in-silico for ventricular pacings utilizing realistic CT-based heart and torso geometries. The proposed approach provided more accurate solution on the ventricular endocardium compared to the conventional potential-based solutions with Tikhonov regularization of the 0th, 1st, and 2nd orders. Furthermore, we show a uniform spatio-temporal behavior of the single layer densities over the heart surface, which could be conveniently employed in the regularization procedure.

Mapping of ventricular arrhythmias using a novel noninvasive epicardial and endocardial electrophysiology system.

INTRODUCTION: The aim of this study was to assess the use of a novel noninvasive epicardial and endocardial electrophysiology system (NEEES) for mapping of ventricular arrhythmias. METHODS: Eight patients (2 females, mean age 50±17 years) with ischemic (n=3) and nonischemic (n=5) cardiomyopathy and inducible ventricular arrhythmias during electrophysiology study were enrolled. Noninvasive mapping of ventricular arrhythmias was performed using the NEEES based on body-surface electrocardiograms and computed tomography imaging data. Arrhythmia patterns were analyzed using noninvasive phase mapping. RESULTS: Macro-reentrant VT circuits were observed in 3 ischemic and 1 nonischemic cardiomyopathy patient, respectively. In the remaining 4 patients, phase mapping revealed relatively stable rotor activity and multiple wavelets. CONCLUSIONS: Noninvasive cardiac mapping was able to visualize the macro-reentrant circuits in patients with scar-related VT. In patients without myocardial scar only polymorphic VT or VF was inducible, and rotor activity and multiple wavelets were observed.

Noninvasive phase mapping of persistent atrial fibrillation in humans: Comparison with invasive catheter mapping.

BACKGROUND: A novel noninvasive epicardial and endocardial electrophysiology system (NEEES) to identify electrical rotors and focal activity in patients with atrial fibrillation (AF) was recently introduced. Comparison of NEEES data with results from invasive mapping is lacking. METHODS: Six male patients (59 ± 11 years) with persistent AF underwent cardiac mapping with the NEEES, which included the creation of isopotential and phase maps. Then patients underwent catheter mapping using a PentaRay NAV catheter and the CARTO 3 system. Signals acquired by the catheter were analyzed by customized software that applied the same phase mapping algorithm as for the NEEES data. RESULTS: In all patients, noninvasive phase mapping revealed short-lived electrical rotors occurring 1.8 ± 0.3 times per second and demonstrating 1-4 (mean 1.2 ± 0.6) rotation cycles. Most of these rotors (72.7%) aggregated in 2-3 anatomical clusters. In two patients, focal excitation from pulmonary veins was observed. Invasive catheter mapping in the dominant rotor aggregation sites and in the three control sites demonstrated the presence of electrical rotors with properties similar to noninvasively detected rotors. Spearman's correlation coefficient between rotor occurrence rate by noninvasive and invasive mapping was 0.97 (p < .0001). Mean rotors' cycle length at dominant aggregation sites, scores of their full rotations, and the proportion of rotors with clockwise rotation were not significantly different between the mapping modalities. CONCLUSION: In patients with persistent AF, phase processing of unipolar electrograms recorded by catheter mapping could reproduce electrical rotors as characterized by NEEES-based phase mapping.

Noninvasive epicardial and endocardial mapping of premature ventricular contractions.

AIMS: The aim of the present study was to estimate the accuracy of a novel non-invasive epicardial and endocardial electrophysiology system (NEEES) for mapping ectopic ventricular depolarizations. METHODS AND RESULTS: The study enrolled 20 patients with monomorphic premature ventricular contractions (PVCs) or ventricular tachycardia (VT). All patients underwent pre-procedural computed tomography or magnetic resonance imaging of the heart and torso. Radiographic data were semi-automatically processed by the NEEES to reconstruct a realistic 3D model of the heart and torso. In the electrophysiology laboratory, body-surface electrodes were connected to the NEEES followed by unipolar EKG recordings during episodes of PVC/VT. The body-surface EKG data were processed by the NEEES using its inverse-problem solution software in combination with anatomical data from the heart and torso. The earliest site of activation as denoted on the NEEES 3D heart model was compared with the PVC/VT origin using a 3D electroanatomical mapping system. The site of successful catheter ablation served as final confirmation. A total of 21 PVC/VT morphologies were analysed and ablated. The chamber of interest was correctly diagnosed non-invasively in 20 of 21 (95%) PVC/VT cases. In 18 of the 21 (86%) cases, the correct ventricular segment was diagnosed. Catheter ablation resulted in acute success in 19 of the 20 (95%) patients, whereas 1 patient underwent successful surgical ablation. During 6 months of follow-up, 19 of the 20 (95%) patients were free from recurrence off antiarrhythmic drugs. CONCLUSION: The NEEES accurately identified the site of PVC/VT origin. Knowledge of the potential site of the PVC/VT origin may aid the physician in planning a successful ablation strategy.

Simultaneous Non-Invasive Epicardial and Endocardial Mapping in Patients With Brugada Syndrome: New Insights Into Arrhythmia Mechanisms.

BACKGROUND: The underlying mechanisms of Brugada syndrome (BrS) are not completely understood. Recent studies provided evidence that the electrophysiological substrate, leading to electrocardiogram abnormalities and/or ventricular arrhythmias, is located in the right ventricular outflow tract (RVOT). The purpose of this study was to examine abnormalities of epicardial and endocardial local unipolar electrograms by simultaneous noninvasive mapping in patients with BrS. METHODS AND RESULTS: Local epicardial and endocardial unipolar electrograms were analyzed using a novel noninvasive epi- and endocardial electrophysiology system (NEEES) in 12 patients with BrS and 6 with right bundle branch block for comparison. Fifteen normal subjects composed the control group. Observed depolarization abnormalities included fragmented electrograms in the anatomical area of RVOT endocardially and epicardially, significantly prolonged activation time in the RVOT endocardium (65±20 vs 38±13 ms in controls; P=0.008), prolongation of the activation-recovery interval in the RVOT epicardium (281±34 vs 247±26 ms in controls; P=0.002). Repolarization abnormalities included a larger area of ST-segment elevation >2 mV and T-wave inversions. Negative voltage gradient (-2.5 to -6.0 mV) between epicardium and endocardium of the RVOT was observed in 8 of 12 BrS patients, not present in patients with right bundle branch block or in controls. CONCLUSIONS: Abnormalities of epicardial and endocardial electrograms associated with depolarization and repolarization properties were found using NEEES exclusively in the RVOT of BrS patients. These findings support both, depolarization and repolarization abnormalities, being operative at the same time in patients with BrS.

Validation of the mapping accuracy of a novel non-invasive epicardial and endocardial electrophysiology system.

AIMS: Use of a non-invasive electrocardiographic mapping system may aid in rapid diagnosis of atrial or ventricular arrhythmias or the detection of ventricular dyssynchrony. The aim of the present study was to validate the mapping accuracy of a novel non-invasive epi- and endocardial electrophysiology system (NEEES). METHODS AND RESULTS: Patients underwent pre-procedural computed tomography or magnetic resonance imaging of the heart and torso. Radiographic data were merged with the data obtained from the NEEES during pacing from implanted pacemaker leads or pacing from endocardial sites using an electroanatomical mapping system (CARTO 3, Biosense Webster). The earliest activation as denoted on the NEEES three-dimensional heart model was compared with the true anatomic location of the tip of the pacemaker lead or the annotated pacing site on the CARTO 3 map. Twenty-nine patients [mean age: 62 ± 11 years, 6/29 (11%) female, 21/29 (72%) with ischaemic cardiomyopathy] were enrolled into the pacemaker verification group. The mean distance from the non-invasively predicted pacing site to the anatomic reference site was 10.8 ± 5.4 mm for the right atrium, 7.7 ± 5.8 mm for the right ventricle, and 7.9 ± 5.7 mm for the left ventricle activated via the coronary sinus lead. Five patients [mean age 65 ± 4 years, 2 (33%) females] underwent CARTO 3 verification study. The mean distance between non-invasively reconstructed pacing site and the reference pacing site was 7.4 ± 2.7 mm for the right atrium, 6.9 ± 2.3 mm for the left atrium, 6.5 ± 2.1 mm for the right ventricle, and 6.4 ± 2.2 for the left ventricle, respectively. CONCLUSION: The novel NEEES was able to correctly identify the site of pacing from various endo- and epicardial sites with high accuracy.

Was Earth ever infected by martian biota? Clues from radioresistant bacteria.

Here we propose that the radioresistance (tolerance to ionizing radiation) observed in several terrestrial bacteria has a martian origin. Multiple inconsistencies with the current view of radioresistance as an accidental side effect of tolerance to desiccation are discussed. Experiments carried out 25 years ago were reproduced to demonstrate that "ordinary" bacteria can develop high radioresistance ability after multiple cycles of exposure to high radiation dosages followed by cycles of recovery of the bacterial population. We argue that "natural" cycles of this kind could have taken place only on the martian surface, and we hypothesize that Mars microorganisms could have developed radioresistance in just several million years' time and, subsequently, have undergone transfer to Earth by way of martian meteorites. Our mechanism implies multiple and frequent exchanges of biota between Mars and Earth.