Introduction: The genesis of atrial fibrillation (AF) and success of AF ablation therapy have been strongly linked with atrial fibrosis. Increasing evidence suggests that patient-specific distributions of fibrosis may determine the locations of electrical drivers (rotors) sustaining AF, but the underlying mechanisms are incompletely understood. This study aims to elucidate a missing mechanistic link between patient-specific fibrosis distributions and AF drivers.Methods: 3D atrial models integrated human atrial geometry, rule-based fiber orientation, region-specific electrophysiology, and AF-induced ionic remodeling. A novel detailed model for an atrial fibroblast was developed, and effects of myocyte-fibroblast (M-F) coupling were explored at single-cell, 1D tissue and 3D atria levels. Left atrial LGE MRI datasets from 3 chronic AF patients were segmented to provide the patient-specific distributions of fibrosis. The data was non-linearly registered and mapped to the 3D atria model. Six distinctive fibrosis levels (0–healthy tissue, 5–dense fibrosis) were identified based on LGE MRI intensity and modeled as progressively increasing M-F coupling and decreasing atrial tissue coupling. Uniform 3D atrial model with diffuse (level 2) fibrosis was considered for comparison.Results: In single cells and tissue, the largest effect of atrial M-F coupling was on the myocyte resting membrane potential, leading to partial inactivation of sodium current and reduction of conduction velocity (CV). In the 3D atria, further to the M-F coupling, effects of fibrosis on tissue coupling greatly reduce atrial CV. AF was initiated by fast pacing in each 3D model with either uniform or patient-specific fibrosis. High variation in fibrosis distributions between the models resulted in varying complexity of AF, with several drivers emerging. In the diffuse fibrosis models, waves randomly meandered through the atria, whereas in each the patient-specific models, rotors stabilized in fibrotic regions. The rotors propagated slowly around the border zones of patchy fibrosis (levels 3–4), failing to spread into inner areas of dense fibrosis.Conclusion: Rotors stabilize in the border zones of patchy fibrosis in 3D atria, where slow conduction enable the development of circuits within relatively small regions. Our results can provide a mechanistic explanation for the clinical efficacy of ablation around fibrotic regions.
Knowledge of atrial wall thickness (AWT) has the potential to provide important information for patient stratification and the planning of interventions in atrial arrhythmias. To date, information about AWT has only been acquired in post-mortem or poor-contrast computed tomography (CT) studies, providing limited coverage and highly variable estimates of AWT. We present a novel contrast agent-free MRI sequence for imaging AWT and use it to create personalized AWT maps and a biatrial atlas. A novel black-blood phase-sensitive inversion recovery protocol was used to image ten volunteers and, as proof of concept, two atrial fibrillation patients. Both atria were manually segmented to create subject-specific AWT maps using an average of nearest neighbors approach. These were then registered non-linearly to generate an AWT atlas. AWT was 2.4 ± 0.7 and 2.7 ± 0.7 mm in the left and right atria, respectively, in good agreement with post-mortem and CT data, where available. AWT was 2.6 ± 0.7 mm in the left atrium of a patient without structural heart disease, similar to that of volunteers. In a patient with structural heart disease, the AWT was increased to 3.1 ± 1.3 mm. We successfully designed an MRI protocol to non-invasively measure AWT and create the first whole-atria AWT atlas. The atlas can be used as a reference to study alterations in thickness caused by atrial pathology. The protocol can be used to acquire personalized AWT maps in a clinical setting and assist in the treatment of atrial arrhythmias.
SummaryPatient-controlled analgesia was introduced in a district general hospital in order to improve postoperative pain control. Techniques of management were developed with effectiveness, safety and practicality as the main objectives. An analysis of the first 1000 patients to use the system is presented. Problems were encountered with slow respiratory rate, monitoring, equipment function and ward management. Identijication of specijic hazards and management problems led to improvements in system safety. Patient-coetroiled analgesia has become the standard technique for postoperative pain control after major surgery in this hospital.
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