Refining the Eikonal Model to Reproduce the Influence of Atrial Tissue Geometry on Conduction Velocity

Atrial fibrillation is responsible for a significant and steadily rising burden. Simultaneously, the treatment options for atrial fibrillation are far from optimal. Personalized simulations of cardiac electrophysiology could assist clinicians in the risk stratification and therapy planning for atrial fibrillation. However, the use of personalized simulations in clinics is currently not possible due to either too high computational costs or non-sufficient accuracy. Eikonal simulations come with low computational costs but cannot replicate the influence of cardiac tissue geometry on the conduction velocity of the wave propagation. Consequently, they currently lack the required accuracy to be applied in clinics. Biophysically detailed simulations on the other hand are accurate but associated with too high computational costs. To tackle this issue, a regression model is created based on biophysically detailed bidomain simulation data. This regression formula calculates the conduction velocity dependent on the thickness and curvature of the heart wall. Afterwards the formula was implemented into the eikonal model with the goal to increase the accuracy of the eikonal model without losing its advantage of computational efficiency. The results of the modified eikonal simulations demonstrate that (i) the local activation times become significantly closer to those of the biophysically detailed bidomain simulations, (ii) the advantage of the eikonal model of a low sensitivity to the resolution of the mesh was reduced further, and (iii) the unrealistic occurrence of endo-epicardial dissociation in simulations was remedied. The results suggest that the accuracy of the eikonal model was significantly increased. At the same time, the additional computational costs caused by the implementation of the regression formula are neglectable. In conclusion, a successful step towards a more accurate and fast computational model of cardiac electrophysiology was achieved

Diffusion Reaction Eikonal Alternant Model: Towards Fast Simulations of Complex Cardiac Arrhythmias

Reaction-diffusion (RD) computer models are suitable to investigate the mechanisms of cardiac arrthymias but not directly applicable in clinical settings due to their computational cost. On the other hand, alternative faster eikonal models are incapable of reproducing reentrant activation when solved by iterative methods. The diffusion reaction eikonal alternant model (DREAM) is a new method in which eikonal and RD models are alternated to allow for reactivation. To solve the eikonal equation, the fast iterative method was modified and embedded into DREAM. Obtained activation times control transmembrane voltage courses in the RD model computing, while repolarization times are provided back to the eikonal model. For a planar wave-front in the center of a 2D patch, DREAM action potentials (APs) have a small overshoot in the upstroke compared to pure RD simulations (monodomain) but similar AP duration. DREAM conduction velocity does not increase near boundaries or stimulated areas as it occurs in RD. Anatomical reentry was reproduced with the S1-S2 protocol. This is the first time that an iterative method is used to solve the eikonal model in a version that admits reactivation. This method can facilitate uptake of computer models in clinical settings. Further improvements will allow to accurately represent even more complex patterns of arrhythmi

Recommender system for ablation lines to treat complex atrial tachycardia

Background and Objective: Planning the optimal ablation strategy for the treatment of complex atrial tachycardia (CAT) is a time consuming task and is error-prone. Recently, directed network mapping, a technology based on graph theory, proved to efficiently identify CAT based solely on data of clinical interventions. Briefly, a directed network was used to model the atrial electrical propagation and reentrant activities were identified by looking for closed-loop paths in the network. In this study, we propose a recommender system, built as an optimization problem, able to suggest the optimal ablation strategy for the treatment of CAT. Methods: The optimization problem modeled the optimal ablation strategy as that one interrupting all reentrant mechanisms while minimizing the ablated atrial surface. The problem was designed on top of directed network mapping. Considering the exponential complexity of finding the optimal solution of the problem, we introduced a heuristic algorithm with polynomial complexity. The proposed algorithm was applied to the data of i) 6 simulated scenarios including both left and right atrial flutter; and ii) 10 subjects that underwent a clinical routine. Results: The recommender system suggested the optimal strategy in 4 out of 6 simulated scenarios. On clinical data, the recommended ablation lines were found satisfactory on 67% of the cases according to the clinician’s opinion, while they were correctly located in 89%. The algorithm made use of only data collected during mapping and was able to process them nearly real-time. Conclusions: The first recommender system for the identification of the optimal ablation lines for CAT, based solely on the data collected during the intervention, is presented. The study may open up interesting scenarios for the application of graph theory for the treatment of CAT

Comparison of Propagation Models and Forward Calculation Methods on Cellular, Tissue and Organ Scale Atrial Electrophysiology

The bidomain model and the finite element method are an established standard to mathematically describe cardiac electrophysiology, but are both suboptimal choices for fast and large-scale simulations due to high computational costs. We investigate to what extent simplified approaches for propagation models (monodomain, reaction-Eikonal and Eikonal) and forward calculation (boundary element and infinite volume conductor) deliver markedly accelerated, yet physiologically accurate simulation results in atrial electrophysiology. Methods: We compared action potential durations, local activation times (LATs), and electrocardiograms (ECGs) for sinus rhythm simulations on healthy and fibrotically infiltrated atrial models. Results: All simplified model solutions yielded LATs and P waves in accurate accordance with the bidomain results. Only for the Eikonal model with pre-computed action potential templates shifted in time to derive transmembrane voltages, repolarization behavior notably deviated from the bidomain results. ECGs calculated with the boundary element method were characterized by correlation coefficients >0.9 compared to the finite element method. The infinite volume conductor method led to lower correlation coefficients caused predominantly by systematic overestimations of P wave amplitudes in the precordial leads. Conclusion: Our results demonstrate that the Eikonal model yields accurate LATs and combined with the boundary element method precise ECGs compared to markedly more expensive full bidomain simulations. However, for an accurate representation of atrial repolarization dynamics, diffusion terms must be accounted for in simplified models. Significance: Simulations of atrial LATs and ECGs can be notably accelerated to clinically feasible time frames at high accuracy by resorting to the Eikonal and boundary element methods

Modelo de Negocio Segmentado Guascas Tradición, Nutrición y Sabor

Con el pasar de los años y el desgaste de los mismos, el cuerpo sufre numerosas transformaciones que hacen que nuestro estilo de vida con el pasar de los años cambie. Por ejemplo, la textura de la piel, la descalcificación de los huesos, la pérdida de flexibilidad, movilidad, sueño y apetito, enfermedades cardíacas y digestivas, entre otras, son el diario vivir de un gran porcentaje de los adultos mayores. Pero, pasamos desapercibido el papel fundamental que cumple una buena alimentación para controlar o aliviar las enfermedades y más, cuando nuestro ritmo de vida se ve apaciguado por la vejez

A Molecular Characterization of the Allelic Expression of the BRCA1 Founder Δ9–12 Pathogenic Variant and Its Potential Clinical Relevance in Hereditary Cancer:International Journal of Molecular Sciences

Hereditary breast and ovarian cancer (HBOC) syndrome is a genetic condition that increases the risk of breast cancer by 80% and that of ovarian cancer by 40%. The most common pathogenic variants (PVs) causing HBOC occur in the BRCA1 gene, with more than 3850 reported mutations in the gene sequence. The prevalence of specific PVs in BRCA1 has increased across populations due to the effect of founder mutations. Therefore, when a founder mutation is identified, it becomes key to improving cancer risk characterization and effective screening protocols. The only founder mutation described in the Mexican population is the deletion of exons 9 to 12 of BRCA1 (BRCA1Δ9–12), and its description focuses on the gene sequence, but no transcription profiles have been generated for individuals who carry this gene. In this study, we describe the transcription profiles of cancer patients and healthy individuals who were heterozygous for PV BRCA1Δ9–12 by analyzing the differential expression of both alleles compared with the homozygous BRCA1 control group using RT–qPCR, and we describe the isoforms produced by the BRCA1 wild-type and BRCA1Δ9–12 alleles using nanopore long-sequencing. Using the Kruskal–Wallis test, our results showed a similar transcript expression of the wild-type allele between the healthy heterozygous group and the homozygous BRCA1 control group. An association between the recurrence and increased expression of both alleles in HBOC patients was also observed. An analysis of the sequences indicated four wild-type isoforms with diagnostic potential for discerning individuals who carry the PV BRCA1Δ9–12 and identifying which of them has developed cancer

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Recurrence of atrial fibrillation following non-cardiac surgery or acute illness:A common but rarely detected complication

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