In-silico modeling of atrial repolarization in normal and atrial fibrillation remodeled state

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and the total number of AF patients is constantly increasing. The mechanisms leading to and sustaining AF are not completely understood yet. Heterogeneities in atrial electrophysiology seem to play an important role in this context. Although some heterogeneities have been used in in-silico human atrial modeling studies, they have not been thoroughly investigated. In this study, the original electrophysiological (EP) models of Courtemanche et al., Nygren et al. and Maleckar et al. were adjusted to reproduce action potentials in 13 atrial regions. The parameter sets were validated against experimental action potential duration data and ECG data from patients with AV block. The use of the heterogeneous EP model led to a more synchronized repolarization sequence in a variety of 3D atrial anatomical models. Combination of the heterogeneous EP model with a model of persistent AF-remodeled electrophysiology led to a drastic change in cell electrophysiology. Simulated Ta-waves were significantly shorter under the remodeling. The heterogeneities in cell electrophysiology explain the previously observed Ta-wave effects. The results mark an important step toward the reliable simulation of the atrial repolarization sequence, give a deeper understanding of the mechanism of atrial repolarization and enable further clinical investigations.     

Modeling and Registration for Electrophysiology Procedures Based on Three-Dimensional Imaging

Computer models of cardiac electrophysiology (EP) can help to better understand the mechanisms of arrhythmias and to guide interventions. However, model adjustment to patient data (personalization) is a required step that is still challenging from clinical data. The progress in the fusion of multimodal data opens up new possibilities in generating patient-specific models of the heart. In this paper, we present the state-of-the-art in multimodal data fusion for EP procedure guidance and how such integrated data can be used to personalize models and guide interventions.     

The transport and distribution of the river load from the Kacza River into the Gulf of Gdańsk (Southern Baltic Sea, Poland)

The results of measurements of suspended sediment and bed load carried by the Kacza River into the Gulf of Gdańsk are discussed. The investigations were conducted in the years 2009–2010 at the Or?owo transect and at the mouth of the Kacza River in the Gulf of Gdańsk. The research has shown that the Kacza River discharged about 673 tons of sediment annually to the Gulf of Gdańsk, with 77% being transported as bed load. The granulometric composition of the river load is dominated by coarse-grained sand fractions.     

Advanced image fusion to overlay coronary sinus anatomy with real-time fluoroscopy to facilitate left ventricular lead implantation in CRT

Background: Failure rate for left ventricular (LV) lead implantation in cardiac resynchronization therapy (CRT) is up to 12%. The use of segmentation tools, advanced image registration software, and high‐fidelity images from computerized tomography (CT) and cardiac magnetic resonance (CMR) of the coronary sinus (CS) can guide LV lead implantation. We evaluated the feasibility of advanced image registration onto live fluoroscopic images to allow successful LV lead placement. Methods: Twelve patients (11 male, 59 ± 16.8 years) undergoing CRT had three‐dimensional (3D) whole‐heart imaging (six CT, six CMR). Eight patients had at least one previously failed LV lead implant. Using segmentation software, anatomical models of the cardiac chambers, CS, and its branches were overlaid onto the live fluoroscopy using a prototype version of the Philips EP Navigator software to guide lead implantation. Results: We achieved high‐fidelity segmentations of cardiac chambers, coronary vein anatomy, and accurate registration between the 3D anatomical models and the live fluoroscopy in all 12 patients confirmed by balloon occlusion angiography. The CS was cannulated successfully in every patient and in 11, an LV lead was implanted successfully. (One patient had no acceptable lead values due to extensive myocardial scar.) Conclusion: Using overlaid 3D segmentations of the CS and cardiac chambers, it is feasible to guide CRT implantation in real time by fusing advanced imaging and fluoroscopy. This enabled successful CRT in a group of patients with previously failed implants. This technology has the potential to facilitate CRT and improve implant success. (PACE 2011; 34:226–234)     

Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection

Autoimmune liver diseases, such as autoimmune hepatitis (AIH) and primary biliary cirrhosis, often have severe consequences for the patient. Because of a lack of appropriate animal models, not much is known about their potential viral etiology. Infection by liver-tropic viruses is one possibility for the breakdown of self-tolerance. Therefore, we infected mice with adenovirus Ad5 expressing human cytochrome P450 2D6 (Ad-2D6). Ad-2D6-infected mice developed persistent autoimmune liver disease, apparent by cellular infiltration, hepatic fibrosis, "fused" liver lobules, and necrosis. Similar to type 2 AIH patients, Ad-2D6-infected mice generated type 1 liver kidney microsomal-like antibodies recognizing the immunodominant epitope WDPAQPPRD of cytochrome P450 2D6 (CYP2D6). Interestingly, Ad-2D6-infected wild-type FVB/N mice displayed exacerbated liver damage when compared with transgenic mice expressing the identical human CYP2D6 protein in the liver, indicating the presence of a stronger immunological tolerance in CYP2D6 mice. We demonstrate for the first time that infection with a virus expressing a natural human autoantigen breaks tolerance, resulting in a chronic form of severe, autoimmune liver damage. Our novel model system should be instrumental for studying mechanisms involved in the initiation, propagation, and precipitation of virus-induced autoimmune liver diseases.     

LV function validation of computer-assisted interventional system for cardiac resyncronisation therapy

Purpose

Cardiac resynchronisation therapy (CRT) is an established treatment for symptomatic patients with heart failure, a prolonged QRS duration, and impaired left ventricular (LV) function; however, non-response rates remain high. Recently proposed computer-assisted interventional platforms for CRT provide new routes to improving outcomes. Interventional systems must process information in an accurate, fast and highly automated way that is easy for the interventional cardiologists to use. In this paper, an interventional CRT platform is validated against two offline diagnostic tools to demonstrate that accurate information processing is possible in the time critical interventional setting.

Methods

The study consisted of 3 healthy volunteers and 16 patients with heart failure and conventional criteria for CRT. Data analysis included the calculation of end-diastolic volume, end-systolic volume, stroke volume and ejection fraction; computation of global volume over the cardiac cycle as well as time to maximal contraction expressed as a percentage of the total cardiac cycle.

Results

The results showed excellent correlation (\(R^{2}\) values of \(>\,0.99\) and Pearson correlation coefficient of \(>\,0.98\)) with comparable offline diagnostic tools.

Conclusion

Results confirm that our interventional system has good accuracy in everyday clinical practice and can be of clinical utility in identification of CRT responders and LV function assessment.

     

Acute pulmonary vein isolation is achieved by a combination of reversible and irreversible atrial injury after catheter ablation: evidence from magnetic resonance imaging

Background- Pulmonary vein reconnection after pulmonary vein isolation is common and is usually associated with recurrences of atrial fibrillation. We used cardiac magnetic resonance imaging after radiofrequency ablation to investigate the hypothesis that acute pulmonary vein isolation results from a combination of irreversible and reversible atrial injury. Methods and Results- Delayed enhancement (DE; representing areas of acute tissue injury/necrosis) and T2-weighted (representing tissue water content, including edema) cardiac magnetic resonance scans were performed before, immediately after (acute), and later than 3 months (late) after pulmonary vein isolation in 25 patients with paroxysmal atrial fibrillation undergoing wide-area circumferential ablation. Images were analyzed as pairs of pulmonary veins to quantify the percentage of circumferential antral encirclement composed of DE, T2, and combined DE+T2 signal. Fourteen of 25 patients were atrial fibrillation free at 11-month follow-up (interquartile range, 8-16 months). These patients had higher DE (71±6.0%) and lower T2 signal (72±7.8%) encirclement on the acute scans compared with recurrences (DE, 55±9.1%; T2, 85±6.3%; P<0.05). Patients maintaining sinus rhythm had a lesser decline in DE between acute and chronic scans compared with recurrences (71±6.0% and 60±5.8% versus 55±9.1% and 34±7.3%, respectively). The percentage of encirclement by a combination of DE+T2 was almost similar in both groups on the acute scans (atrial fibrillation free, 89±5.4%; recurrences, 92±4.8%) but different on the chronic scans (60±5.7% versus 34±7.3%). Conclusions- The higher T2 signal on acute scans and greater decline in DE on chronic imaging in patients with recurrences suggest that they have more reversible tissue injury, providing a potential mechanism for pulmonary vein reconnection, resulting in arrhythmia recurrence.