Baseline elevation and reduction in cardiac electrical instability assessed by quantitative T-wave alternans in patients with drug-resistant epilepsy treated with vagus nerve stimulation in the AspireSR E-36 trial

Objective: Reports of cardiac arrhythmias and cardiac pathology at postmortem examination of patients with epilepsy suggest a possible cardiac component of risk for sudden unexpected death in epilepsy (SUDEP). T-wave alternans (TWA) is an established marker of cardiac electrical instability and risk for sudden death in patients with cardiovascular disease. We determined the TWA level before vagus nerve stimulation (VNS) system implantation and subsequently the effect of VNS on TWA in patients with drug-resistant epilepsy. Methods: Patients (n = 28) from the Seizure Detection and Automatic Magnet Mode Performance Study (E-36), a clinical trial of the AspireSR (R) VNS Therapy System (R) (NCT01325623), were monitored with ambulatory electrocardiograms (ECGs) similar to 2 weeks before de novo VNS system implantation and following 2- to 4-week VNS titration during a protocol-specified 3- to 5-day epilepsy monitoring unit stay with concurrent EEG/ECG recordings. The TWA level was assessed interictally by the Modified Moving Average (MMA) method. Results: At preimplantation baseline, TWA was elevated above the 47-mu V abnormality cutpoint in 23 (82%) patients with drug-resistant epilepsy. In 16 (70%) patients, TWA level was reduced during VNS treatment to <47 mu V, thereby converting positive TWA test results to negative. Peak TWA level in all 28 patients improved (group mean, 43%, from 72 +/- 4.3 to 41 +/- 2.3 mu V; p < 0.0001). Vagus nerve stimulation was not associated with reduced heart rate (77 +/- 1.4 to 75 +/- 1.4 beats/min; p = 0.18). Heart rate variability was unchanged. Significance: These findings suggest significant interictal cardiac electrical instability in this population of patients with drug-resistant epilepsy and suggest that VNS may be a novel approach to reducing risk

Air Pollution and ST-Segment Depression in Elderly Subjects

Increased levels of daily ambient particle pollution have been associated with increased risk of cardiovascular morbidity. Black carbon (BC) is a measure of the traffic-related component of particles. We investigated associations between ambient pollution and ST-segment levels in a repeated-measures study including 269 observations on 24 active Boston residents 61–88 years of age, each observed up to 12 times from June through September 1999. The protocol involved continuous Holter electrocardiogram monitoring including 5 min of rest, 5 min of standing, 5 min of exercise outdoors, 5 min of recovery, and 20 cycles of paced breathing. Pollution-associated ST-depression was estimated for a 10th- to 90th-percentile change in BC. We calculated the average ST-segment level, referenced to the P-R isoelectric values, for each portion of the protocol. The mean BC level in the previous 12 hr, and the BC level 5 hr before testing, predicted ST-segment depression in most portions of the protocol, but the effect was strongest in the postexercise periods. During post-exercise rest, an elevated BC level was associated with −0.1 mm ST-segment depression (p = 0.02 for 12-hr mean BC; p = 0.001 for 5-hr BC) in continuous models. Elevated BC also predicted increased risk of ST-segment depression ≥0.5 mm among those with at least one episode of that level of ST-segment depression. Carbon monoxide was not a confounder of this association. ST-segment depression, possibly representing myocardial ischemia or inflammation, is associated with increased exposure to particles whose predominant source is traffic

Prediction of sudden cardiac death with automated high-throughput analysis of heterogeneity in standard resting 12-lead electrocardiograms

BACKGROUND Heterogeneity of depolarization and repolarization underlies the development of lethal arrhythmias. OBJECTIVE We investigated whether quantification of spatial depolarization and repolarization heterogeneity identifies individuals at risk for sudden cardiac death (SCD). METHODS Spatial R-, J-, and T-wave heterogeneity (RWH, JWH, and TWH, respectively) was analyzed using automated second central moment analysis of standard digital 12-lead electrocardiograms in 5618 adults (2588, 46% men; mean +/- SEM age 50.9 +/- 0.2 years), who took part in the epidemiological Health 2000 Survey as representative of the entire Finnish adult population. RESULTS During the follow-up period of 7.7 +/- 0.2 years, a total of 72 SCDs occurred (1.3%), with an average yearly incidence rate of 0.17% per year. Increased RWH, JWH, and TWH in left precordial leads (V-4-V-6) were univariately associated with SCD (P = 102 mu V) was associated with a 1.7-fold adjusted relative risk for SCD (95% confidence interval [CI] 1.0-2.9; P = .048) and increased JWH (>= 123 mu V) with a 2.0-fold adjusted relative risk for SCD (95% CI 1.2-3.3; P = .006). When both TWH and JWH were above the threshold, the adjusted relative risk for SCD was 2.9-fold (95% CI 1.5-5.7; P = .002). When RWH (>= 470 mu V), JWH, and TWH were all above the threshold, the adjusted relative risk for SCD was 3.2-fold (95% CI 1.4-7.1; P = .009). CONCLUSION Second central moment analysis of standard resting 12-lead electrocardiographic morphology provides an ultrarapid means for the automated measurement of spatial RWH, JWH, and TWH, enabling analysis of high subject volumes and screening for SCD risk in the general population.Peer reviewe

Atrial septum fat deposition and atrial anatomy assessed by cardiac magnetic resonance: relationship to atrial electrophysiology

To assess the prevalence of fat deposition in the atrial septum with and its relationship with 12-lead electrocardiogram (ECG) atrial parameters (PR interval, P wave duration) and the presence of atrial fibrillation

Theoretical and experimental investigation into the structure and dynamics of the interstitial matrix of the rat mesentery through two-dimensional microspectrophotometry

Starling first described the important role of plasma proteins in determining fluid distribution between vascular and extravascular spaces. Recently evidence has become available to suggest that the distribution of plasma proteins in perivascular spaces is not uniform as has always been assumed. We developed, validated, and applied a new technique of two dimensional microspectrophotometry to obtain the spatial distribution of water, plasma proteins, collagen in the vascular and avascular regions of the extracellular matrix of rat mesentery tissue. Multispectral (280 nm, 320 nm, 705 nm, 800 nm 1500 nm), 360 um x 360 um images of selected tissue regions were digitized into 512 x 512 pixel images of 8 bits resolution. Estimation of the nonspecific absorption and wavelength dependent scattering from 320 nm, 705 nm images allowed calculation of the tissue protein and tissue collagen distribution images from the 280 nm absorbance image. Water distribution images were calculated in a similar manner from 800 nm, 1500 nm absorbance images. Protein concentration averages (1.88 $\pm$ SD 0.8 g/dl) calculated with a scattering correction are not significantly different (p $\u3c$ 0.2) than direct measurement by electrophoresis (1.8 $\pm$ SD 0.2 g/dl). The 320 nm correction of many single beam microspectrophotometry studies yields a value (4.29 g/dl) which is significantly (p $\u3c$ 0.001) too high. The scattering corrected images show clear detail, apparent protein aggregation, straight fiber like collagen absorption. Two way ANOVA analysis (16 x 16 sections) of avascular tissue show significant spatial variation (P $\u3e$.999). Fourier analysis shows more collagen-protein organization near blood vessels. Venule radial protein gradients are significantly longer than arterioles (t = 4.84, p $\u3c$ 0.005) but not exchange vessels (t = 1.32, p $\u3c$ 0.4). Venule perivascular protein (3.73 $\pm$ 1.56 g/dl) concentration is significantly higher than for exchange vessels (2.39 $\pm$ 0.26 g/dl, t = 2.23, p $\u3c$ 0.1) or arterioles 2.17 $\pm$ 0.19 g/dl, t = 2.6, p $\u3c$ 0.05). Diffusion limited aggregation modeling yields protein distributions similar to that found in perivascular tissue. Tunnels (3 to 4 g/dl), with slowly decaying radial gradients of protein suggesting an absence of walls, have been found near some exchange vessels. Injection of saline boluses indicates that the tunnels are also a preferential water path. Thus there appears to be a great deal of organization and structure in tissue regions assumed to be homogeneous