Causal Unit of Rotors in a Cardiac System

The heart exhibits complex systems behaviors during atrial fibrillation (AF), where the macroscopic collective behavior of the heart causes the microscopic behavior. However, the relationship between the downward causation and scale is nonlinear. We describe rotors in multiple spatiotemporal scales by generating a renormalization group from a numerical model of cardiac excitation, and evaluate the causal architecture of the system by quantifying causal emergence. Causal emergence is an information-theoretic metric that quantifies emergence or reduction between microscopic and macroscopic behaviors of a system by evaluating effective information at each spatiotemporal scale. We find that there is a spatiotemporal scale at which effective information peaks in the cardiac system with rotors. There is a positive correlation between the number of rotors and causal emergence up to the scale of peak causation. In conclusion, one can coarse-grain the cardiac system with rotors to identify a macroscopic scale at which the causal power reaches the maximum. This scale of peak causation should correspond to that of the AF driver, where networks of cardiomyocytes serve as the causal units. Those causal units, if identified, can be reasonable therapeutic targets of clinical intervention to cure AF.Comment: 19 pages, 9 figures. arXiv admin note: text overlap with arXiv:1711.1012

Accuracy of prediction of infarct-related arrhythmic circuits from image-based models reconstructed from low and high resolution MRI.

Identification of optimal ablation sites in hearts with infarct-related ventricular tachycardia (VT) remains difficult to achieve with the current catheter-based mapping techniques. Limitations arise from the ambiguities in determining the reentrant pathways location(s). The goal of this study was to develop experimentally validated, individualized computer models of infarcted swine hearts, reconstructed from high-resolution ex-vivo MRI and to examine the accuracy of the reentrant circuit location prediction when models of the same hearts are instead reconstructed from low clinical-resolution MRI scans. To achieve this goal, we utilized retrospective data obtained from four pigs ~10 weeks post infarction that underwent VT induction via programmed stimulation and epicardial activation mapping via a multielectrode epicardial sock. After the experiment, high-resolution ex-vivo MRI with late gadolinium enhancement was acquired. The Hi-res images were downsampled into two lower resolutions (Med-res and Low-res) in order to replicate image quality obtainable in the clinic. The images were segmented and models were reconstructed from the three image stacks for each pig heart. VT induction similar to what was performed in the experiment was simulated. Results of the reconstructions showed that the geometry of the ventricles including the infarct could be accurately obtained from Med-res and Low-res images. Simulation results demonstrated that induced VTs in the Med-res and Low-res models were located close to those in Hi-res models. Importantly, all models, regardless of image resolution, accurately predicted the VT morphology and circuit location induced in the experiment. These results demonstrate that MRI-based computer models of hearts with ischemic cardiomyopathy could provide a unique opportunity to predict and analyze VT resulting for from specific infarct architecture, and thus may assist in clinical decisions to identify and ablate the reentrant circuit(s)

Modeling the Heart as a Communication System

Electrical communication between cardiomyocytes can be perturbed during arrhythmia, but these perturbations are not captured by conventional electrocardiographic metrics. We developed a theoretical framework to quantify electrical communication using information theory metrics in 2-dimensional cell lattice models of cardiac excitation propagation. The time series generated by each cell was coarse-grained to 1 when excited or 0 when resting. The Shannon entropy for each cell was calculated from the time series during four clinically important heart rhythms: normal heartbeat, anatomical reentry, spiral reentry, and multiple reentry. We also used mutual information to perform spatial profiling of communication during these cardiac arrhythmias. We found that information sharing between cells was spatially heterogeneous. In addition, cardiac arrhythmia significantly impacted information sharing within the heart. Entropy localized the path of the drifting core of spiral reentry, which could be an optimal target of therapeutic ablation. We conclude that information theory metrics can quantitatively assess electrical communication among cardiomyocytes. The traditional concept of the heart as a functional syncytium sharing electrical information cannot predict altered entropy and information sharing during complex arrhythmia. Information theory metrics may find clinical application in the identification of rhythm-specific treatments which are currently unmet by traditional electrocardiographic techniques.Comment: 26 pages (including Appendix), 6 figures, 8 videos (not uploaded due to size limitation

Profile of Blood Glucose in Diabetic Patient Suffered from Diabetic Foot Osteomyelitis with Effective Low Carbohydrate Diet

The case was 52-year-old female with type 2 diabetes mellitus (T2DM) for 10-years. She complained of the decreased sensation of right lower foot, and revealed diabetic foot infection (DFI) and/or diabetic foot osteomyelitis (DFO) at right 1st proximal phalanx. Various data included body mass index (BMI) 33.3 kg/m2, HbA1c 11.4%, blood glucose 430 mg/dL, WBC 12100 /μL, C-reactive Protein (CRP) 13.5 mg/dL. On admission (day 1), she was started by 4 times of injection (Aspart and Glargin) with glucose profile 200-500 mg/dL. Surgical amputation of the right toe was performed between 1st metatarsal and proximal phalanx (day 17). Then, blood glucose profile decreased moderately. After discharge of the hospital, super-Low Carbohydrate Diet (LCD) was started without Aspart (day 37). Consequently, glucose profile was normalized with HbA1c 6.3% on (day 77). Consequently, LCD was evaluated to be effective for glucose variability in this case and some related discussion was described