Bariatric surgery partially reverses subclinical proarrhythmic structural, electrophysiological, and autonomic changes in obesity.

BACKGROUND: Obesity confers higher risks of cardiac arrhythmias. The extent to which weight loss reverses subclinical proarrhythmic adaptations in arrhythmia-free obese individuals is unknown. OBJECTIVE: The purpose of this study was to study structural, electrophysiological, and autonomic remodeling in arrhythmia-free obese patients and their reversibility with bariatric surgery using electrocardiographic imaging (ECGi). METHODS: Sixteen arrhythmia-free obese patients (mean age 43 ± 12 years; 13 females; BMI 46.7 ± 5.5 kg/m2) had ECGi pre-bariatric surgery, of whom 12 had ECGi postsurgery (BMI 36.8 ± 6.5 kg/m2). Sixteen age- and sex-matched lean healthy individuals (mean age 42 ± 11 years; BMI 22.8 ± 2.6 kg/m2) acted as controls and had ECGi only once. RESULTS: Obesity was associated with structural (increased epicardial fat volumes and left ventricular mass), autonomic (blunted heart rate variability), and electrophysiological (slower atrial conduction and steeper ventricular repolarization gradients) remodeling. After bariatric surgery, there was partial structural reverse remodeling, with a reduction in epicardial fat volumes (68.7 cm3 vs 64.5 cm3; P = .0010) and left ventricular mass (33 g/m2.7 vs 25 g/m2.7; P < .0005). There was also partial electrophysiological reverse remodeling with a reduction in mean spatial ventricular repolarization gradients (26 mm/ms vs 19 mm/ms; P = .0009), although atrial activation remained prolonged. Heart rate variability, quantified by standard deviation of successive differences in R-R intervals, was also partially improved after bariatric surgery (18.7 ms vs 25.9 ms; P = .017). Computational modeling showed that presurgery obese hearts had a larger window of vulnerability to unidirectional block and had an earlier spiral-wave breakup with more complex reentry patterns than did postsurgery counterparts. CONCLUSION: Obesity is associated with adverse electrophysiological, structural, and autonomic remodeling that is partially reversed after bariatric surgery. These data have important implications for bariatric surgery weight thresholds and weight loss strategies.

Optimization of anti-tachycardia pacing efficacy through scar-specific delivery and minimization of re-initiation: a virtual study on a cohort of infarcted porcine hearts.

AIMS: Anti-tachycardia pacing (ATP) is a reliable electrotherapy to painlessly terminate ventricular tachycardia (VT). However, ATP is often ineffective, particularly for fast VTs. The efficacy may be enhanced by optimized delivery closer to the re-entrant circuit driving the VT. This study aims to compare ATP efficacy for different delivery locations with respect to the re-entrant circuit, and further optimize ATP by minimizing failure through re-initiation. METHODS AND RESULTS: Seventy-three sustained VTs were induced in a cohort of seven infarcted porcine ventricular computational models, largely dominated by a single re-entrant pathway. The efficacy of burst ATP delivered from three locations proximal to the re-entrant circuit (septum) and three distal locations (lateral/posterior left ventricle) was compared. Re-initiation episodes were used to develop an algorithm utilizing correlations between successive sensed electrogram morphologies to automatically truncate ATP pulse delivery. Anti-tachycardia pacing was more efficacious at terminating slow compared with fast VTs (65 vs. 46%, P = 0.000039). A separate analysis of slow VTs showed that the efficacy was significantly higher when delivered from distal compared with proximal locations (distal 72%, proximal 59%), being reversed for fast VTs (distal 41%, proximal 51%). Application of our early termination detection algorithm (ETDA) accurately detected VT termination in 79% of re-initiated cases, improving the overall efficacy for proximal delivery with delivery inside the critical isthmus (CI) itself being overall most effective. CONCLUSION: Anti-tachycardia pacing delivery proximal to the re-entrant circuit is more effective at terminating fast VTs, but less so slow VTs, due to frequent re-initiation. Attenuating re-initiation, through ETDA, increases the efficacy of delivery within the CI for all VTs.

The impact of wall thickness and curvature on wall stress in patient-specific electromechanical models of the left atrium.

The left atrium (LA) has a complex anatomy with heterogeneous wall thickness and curvature. The anatomy plays an important role in determining local wall stress; however, the relative contribution of wall thickness and curvature in determining wall stress in the LA is unknown. We have developed electromechanical finite element (FE) models of the LA using patient-specific anatomical FE meshes with rule-based myofiber directions. The models of the LA were passively inflated to 10mmHg followed by simulation of the contraction phase of the atrial cardiac cycle. The FE models predicted maximum LA volumes of 156.5 mL, 99.3 mL and 83.4 mL and ejection fractions of 36.9%, 32.0% and 25.2%. The median wall thickness in the 3 cases was calculated as [Formula: see text] mm, [Formula: see text] mm, and [Formula: see text] mm. The median curvature was determined as [Formula: see text] [Formula: see text], [Formula: see text], and [Formula: see text]. Following passive inflation, the correlation of wall stress with the inverse of wall thickness and curvature was 0.55-0.62 and 0.20-0.25, respectively. At peak contraction, the correlation of wall stress with the inverse of wall thickness and curvature was 0.38-0.44 and 0.16-0.34, respectively. In the LA, the 1st principal Cauchy stress is more dependent on wall thickness than curvature during passive inflation and both correlations decrease during active contraction. This emphasizes the importance of including the heterogeneous wall thickness in electromechanical FE simulations of the LA. Overall, simulation results and sensitivity analyses show that in complex atrial anatomy it is unlikely that a simple anatomical-based law can be used to estimate local wall stress, demonstrating the importance of FE analyses.

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

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

The role of photon scattering in optical signal distortion during arrhythmia and defibrillation.

Optical mapping of arrhythmias and defibrillation provides important insights; however, a limitation of the technique is signal distortion due to photon scattering. The goal of this experimental/simulation study is to investigate the role of three-dimensional photon scattering in optical signal distortion during ventricular tachycardia (VT) and defibrillation. A three-dimensional realistic bidomain rabbit ventricular model was combined with a model of photon transport. Shocks were applied via external electrodes to induce sustained VT, and transmembrane potentials (V(m)) were compared with synthesized optical signals (V(opt)). Fluorescent recordings were conducted in isolated rabbit hearts to validate simulation results. Results demonstrate that shock-induced membrane polarization magnitude is smaller in V(opt) and in experimental signals as compared to V(m). This is due to transduction of potentials from weakly polarized midmyocardium to the epicardium. During shock-induced reentry and in sustained VT, photon scattering, combined with complex wavefront dynamics, results in optical action potentials near a filament exhibiting i), elevated resting potential, ii), reduced amplitude relative to pacing, and iii), dual-humped morphologies. A shift of up to 4 mm in the phase singularity location was observed in V(opt) maps when compared to V(m). This combined experimental/simulation study provides an interpretation of optical recordings during VT and defibrillation.

Theatre: A software tool for detailed comparative analysis and visualization of genomic sequence.

Theatre is a web-based computing system designed for the comparative analysis of genomic sequences, especially with respect to motifs likely to be involved in the regulation of gene expression. Theatre is an interface to commonly used sequence analysis tools and biological sequence databases to determine or predict the positions of coding regions, repetitive sequences and transcription factor binding sites in families of DNA sequences. The information is displayed in a manner that can be easily understood and can reveal patterns that might not otherwise have been noticed. In addition to web-based output, Theatre can produce publication quality colour hardcopies showing predicted features in aligned genomic sequences. A case study using the p53 promoter region of four mammalian species and two fish species is described. Unlike the mammalian sequences the promoter regions in fish have not been previously predicted or characterized and we report the differences in the p53 promoter region of four mammals and that predicted for two fish species. Theatre can be accessed at http://www.hgmp.mrc.ac.uk/Registered/Webapp/theatre/.