Arrhythmogenic Manifestations of Chagas Disease: Perspectives From the Bench to Bedside.

Chagas cardiomyopathy caused by infection with the intracellular parasite Trypanosoma cruzi is the most common and severe expression of human Chagas disease. Heart failure, systemic and pulmonary thromboembolism, arrhythmia, and sudden cardiac death are the principal clinical manifestations of Chagas cardiomyopathy. Ventricular arrhythmias contribute significantly to morbidity and mortality and are the major cause of sudden cardiac death. Significant gaps still exist in the understanding of the pathogenesis mechanisms underlying the arrhythmogenic manifestations of Chagas cardiomyopathy. This article will review the data from experimental studies and translate those findings to draw hypotheses about clinical observations. Human- and animal-based studies at molecular, cellular, tissue, and organ levels suggest 5 main pillars of remodeling caused by the interaction of host and parasite: immunologic, electrical, autonomic, microvascular, and contractile. Integrating these 5 remodeling processes will bring insights into the current knowledge in the field, highlighting some key features for future management of this arrhythmogenic disease.

Atherosclerotic cardiovascular disease events among adults with high predicted risk without established risk factors.

Objective: Age is the strongest contributor to 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk. Some older adults have a predicted ASCVD risk ≥7.5 %, without established risk factors. We sought to compare ASCVD incidence among adults with predicted ASCVD risk ≥7.5 %, with and without established ASCVD risk factors, to adults with predicted risk <7.5 %. Methods: We analyzed data from REasons for Geographic and Racial Differences in Stroke study participants, 45-79 years old, without ASCVD or diabetes, not taking statins and with low-density lipoprotein cholesterol 70-189 mg/dL. Participants were categorized into 3 groups based on their 10-year predicted ASCVD risk and presence of established risk factors: <7.5 %, ≥7.5 % with established risk factors and ≥7.5 % without established risk factors. Established risk factors included smoking, systolic blood pressure ≥130 mmHg or antihypertensive medication use, total cholesterol ≥200 mg/dL, or high-density lipoprotein cholesterol <50 mg/dL for women (<40 mg/dL for men). Participants were followed for ASCVD events. Results: Among 11,115 participants, 911 incident ASCVD events occurred over a median of 11.1 years. ASCVD incidence rates were 3.6, 12.8, and 9.8 per 1,000 person-years for participants with predicted risk <7.5 %, predicted risk ≥7.5 % with established risk factors and predicted risk ≥7.5 % without established risk factors, respectively. Compared to adults with predicted risk <7.5 %, hazard ratios for incident ASCVD in participants with risk ≥7.5 % with and without established risk factors were 3.58 (95 %CI 3.03 - 4.21) and 2.72 (95 %CI 1.91-3.88), respectively. Conclusions: Adults with a 10-year predicted ASCVD risk ≥7.5 % but without established risk factors had a high ASCVD incidence.

Mouse visual cortex as a limited resource system that self-learns an ecologically-general representation.

Studies of the mouse visual system have revealed a variety of visual brain areas that are thought to support a multitude of behavioral capacities, ranging from stimulus-reward associations, to goal-directed navigation, and object-centric discriminations. However, an overall understanding of the mouse's visual cortex, and how it supports a range of behaviors, remains unknown. Here, we take a computational approach to help address these questions, providing a high-fidelity quantitative model of mouse visual cortex and identifying key structural and functional principles underlying that model's success. Structurally, we find that a comparatively shallow network structure with a low-resolution input is optimal for modeling mouse visual cortex. Our main finding is functional-that models trained with task-agnostic, self-supervised objective functions based on the concept of contrastive embeddings are much better matches to mouse cortex, than models trained on supervised objectives or alternative self-supervised methods. This result is very much unlike in primates where prior work showed that the two were roughly equivalent, naturally leading us to ask the question of why these self-supervised objectives are better matches than supervised ones in mouse. To this end, we show that the self-supervised, contrastive objective builds a general-purpose visual representation that enables the system to achieve better transfer on out-of-distribution visual scene understanding and reward-based navigation tasks. Our results suggest that mouse visual cortex is a low-resolution, shallow network that makes best use of the mouse's limited resources to create a light-weight, general-purpose visual system-in contrast to the deep, high-resolution, and more categorization-dominated visual system of primates.

Impact of race on outcomes from catheter ablation of ventricular tachycardia in structural heart disease: A prospective registry from south metropolitan Chicago.

Background: Whether racial disparities in outcomes are present after catheter ablation for scar-related ventricular tachycardia (VT) is not known. Objective: The purpose of this study was to examine whether racial differences exist in outcomes for patients undergoing VT ablation. Methods: From March 2016 through April 2021, consecutive patients undergoing catheter ablation for scar-related VT at the University of Chicago were prospectively enrolled. The primary outcome was VT recurrence, with secondary outcome of mortality alone and composite endpoint of left ventricular assist device placement, heart transplant, or mortality. Results: A total of 258 patients were analyzed: 58 (22%) self-identified as Black, and 113 (44%) had ischemic cardiomyopathy. Black patients had significantly higher rates of hypertension (HTN), chronic kidney disease (CKD), and VT storm at presentation. At 7 months, Black patients experienced higher rates of VT recurrence (P = .009). However, after multivariable adjustment, there were no observed differences in VT recurrence (adjusted hazard ratio [aHR] 1.65; 95% confidence interval [CI] 0.91-2.97; P = .10), all-cause mortality (aHR 0.49; 95% CI 0.21-1.17; P = .11), or composite events (aHR 0.76; 95% CI 0.37-1.54; P = .44) between Black and non-Black patients. Conclusion: In this diverse prospective registry of patients undergoing catheter ablation for scar-related VT, Black patients experienced higher rates of VT recurrence compared to non-Black patients. When adjusted for highly prevalent HTN, CKD, and VT storm, Black patients had comparable outcomes as non-Black patients.

Cardiac resynchronization considerations in left bundle branch block.

Cardiac resynchronization therapy (CRT) via biventricular pacing (BiVP) is an established treatment for patients with left ventricular systolic heart failure and intraventricular conduction delay resulting in wide QRS. Seminal trials demonstrating mortality benefit from CRT were conducted in patients with wide left bundle branch block (LBBB) pattern on electrocardiogram (ECG) and evidence of clinical heart failure. The presence of conduction block was assumed to correlate with commonly applied criteria for LBBB. More recent data has challenged this assertion, revealing that LBBB pattern may include distinct underlying pathophysiology, including patients with complete conduction block, either at the left-sided His fibers or the proximal left bundle, intact Purkinje activation with wide LBBB-like QRS, and patients demonstrating both proximal block and distal delay. Currently, BiVP-CRT is indicated for all QRS duration ≥150 ms and may be considered for BBB patterns from 130 to 149 ms with robust clinical data to support its use. Despite this, however, there remains a significant number of non-responders to BVP. Conduction system pacing (CSP) has emerged as an alternative approach to deliver CRT and correct QRS in patients with conduction block. Newer hybrid approaches which combine CSP and traditional BiVP-CRT and may hold promise for patients with IP or mixed-level block. As various approaches to CRT continue to be studied, physiologic phenotyping of the LBBB pattern remains an important consideration.

The Transulnar Approach to Coronary Angiography and Intervention: Assessing the Anatomy of the Ulnar Artery Using Angiography.

BACKGROUND: The transulnar approach (TUA) has been proposed as a safe alternative to the more established transradial approach (TRA) for cardiac catheterization. However, no study has assessed the anatomy and variability of the ulnar artery using angiography. METHODS: A retrospective analysis of patients who underwent transradial cardiac catheterization during routine clinical care was conducted. Both quantitative and qualitative measurements of artery diameter were collected. RESULTS: Among 700 consecutive patients, mean distal ulnar artery diameter (UAD) was larger in men (3.2 ± 0.9 mm) compared with women (2.7 ± 0.7 mm; P<.001). UAD was larger than radial artery diameter (RAD) at all measured sites (distal ulnar, 3.0 ± 0.8 mm; distal radial, 2.9 ± 0.7 mm; P=.046). Compared with the radial artery, the ulnar artery had more atresia (4.3% ulnar vs 0% radial; P<.001), fewer loops (0.6% ulnar vs 2.4% radial; P<.01), and less spasm (2.7% ulnar vs 23.4% radial; P<.001). UAD had more variability (distal variance, 0.68) as compared with the RAD (distal variance, 0.53; P<.001). CONCLUSION: We found that the ulnar artery has a larger diameter, fewer loops, and less spasm, but more variance than the radial artery. Additionally, males have larger ulnar arteries than women. These findings have implications on the application of TUA either as an alternative to TRA or as the primary point of access.

Increasing neural network robustness improves match to macaque V1 eigenspectrum, spatial frequency preference and predictivity.

Task-optimized convolutional neural networks (CNNs) show striking similarities to the ventral visual stream. However, human-imperceptible image perturbations can cause a CNN to make incorrect predictions. Here we provide insight into this brittleness by investigating the representations of models that are either robust or not robust to image perturbations. Theory suggests that the robustness of a system to these perturbations could be related to the power law exponent of the eigenspectrum of its set of neural responses, where power law exponents closer to and larger than one would indicate a system that is less susceptible to input perturbations. We show that neural responses in mouse and macaque primary visual cortex (V1) obey the predictions of this theory, where their eigenspectra have power law exponents of at least one. We also find that the eigenspectra of model representations decay slowly relative to those observed in neurophysiology and that robust models have eigenspectra that decay slightly faster and have higher power law exponents than those of non-robust models. The slow decay of the eigenspectra suggests that substantial variance in the model responses is related to the encoding of fine stimulus features. We therefore investigated the spatial frequency tuning of artificial neurons and found that a large proportion of them preferred high spatial frequencies and that robust models had preferred spatial frequency distributions more aligned with the measured spatial frequency distribution of macaque V1 cells. Furthermore, robust models were quantitatively better models of V1 than non-robust models. Our results are consistent with other findings that there is a misalignment between human and machine perception. They also suggest that it may be useful to penalize slow-decaying eigenspectra or to bias models to extract features of lower spatial frequencies during task-optimization in order to improve robustness and V1 neural response predictivity.

Association between diet quality and incident cardiovascular disease stratified by body mass index.

OBJECTIVE: Diet quality is a significant contributor to cardiovascular disease (CVD) development given its substantial influence on important downstream CVD mediators such as weight. However, it is unclear if there are additional pathways between diet quality and incident CVD independent of weight. We sought to determine if higher diet quality was associated with lower CVD risk stratified by BMI categories. METHODS: Prospective cohort data from the Lifetime Risk Pooling Project (LRPP) was analyzed. Diet data from 6 US cohorts were harmonized. The alternative Healthy Eating Index-2010 (aHEI-2010) score was calculated for each participant. Within each cohort, participants were divided into aHEI-2010 quintiles. The primary outcome of interest was composite incident CVD event including coronary heart disease, stroke, heart failure, and CVD death. Cox regression analysis was performed separately for three BMI strata: 18.5-24.9, 25-29.9, and ≥ 30 kg/m2. RESULTS: A total of 30,219 participants were included. During a median follow-up of 16.2 years, there were a total of 7,021 CVD events. An inverse association between aHEI-2010 score and incident CVD was identified among participants who were normal weight (comparing highest quintile with lowest quintile: adjusted hazard ratio [95% confidence interval] 0.57 [0.50 - 0.66]) and among participants with overweight (0.69 [0.61 - 0.77]). aHEI-2010 score was not associated with CVD among participants with obesity (0.97 [0.84 - 1.13]). CONCLUSIONS: Among adults in the United States, higher diet quality as measured by aHEI-2010 was significantly associated with lower risk of incident CVD among individuals with normal weight and overweight but not obesity.

A retrospective analysis of high sensitivity cardiac troponin-T ranges in non-myocardial infarction emergency department visits.

INTRODUCTION: Current evidence suggests that high sensitivity cardiac troponin-T (hs-cTnT) values differ based on sex, race, age, and kidney function. However, most studies examining the relationship of hs-cTnT and these individual factors are in healthy participants, leading to difficulty in interpreting hs-cTnT values in the Emergency Department (ED) setting. We seek to examine the relationship between hs-cTnT values and sex, race, age, and kidney function in a contemporary, urban academic setting. METHODS: ED visits from June 2018 through April 2019 with at least 1 hs-cTnT and no diagnosis of acute myocardial infarction (AMI) at an academic medical center in the south side of Chicago were retrospectively analyzed. Median hs-cTnT values were stratified by sex (male or female), race (African American or Caucasian), age, estimated glomerular filtration rate (eGFR), and stage of chronic kidney disease. RESULTS: 9679 encounters, representing 7989 distinct patients, were included for analysis (age 58 ± 18 years, 59% female, 85% black). Males had significantly higher median hs-cTnT values than females (16 [8-34] vs. 9 [6-22] ng/L, p < 0.001), African Americans had a significantly lower median value than Caucasians (10 [6-24] vs. 15 [6-29] ng/L, p < 0.001), and those with atrial fibrillation (27 [16-48] vs. 9 [6-19] ng/L, p < 0.001) and heart failure (28 [14-48] vs. 8 [6-15] ng/L, p < 0.001) had higher median values than those without. Median hs-cTnT values increased significantly with increased age and decreased eGFR. All relationships continued to be significant even after multivariable regression of sex, age, race, eGFR, presence of atrial fibrillation, and presence of heart failure (p < 0.01). CONCLUSIONS: Analysis of hs-cTnT in non-AMI patients during ED encounters showed that males have higher values than females, African Americans have lower values than Caucasians, those with atrial fibrillation and heart failure have higher values than those without, and that older age and lower eGFR were associated with higher median values.

Takotsubo Syndrome Presenting as Cardiogenic Shock in Patients With COVID-19: A Case Series and Review of Current Literature.

Takotsubo's syndrome (TTS) is a form of stress cardiomyopathy with a relatively benign long-term course, but may lead to arrhythmias and cardiogenic shock in the acute setting. Despite a recent rise in suspected stress-induced cardiomyopathy, the relationship between the novel coronavirus disease 19 (COVID-19) and TTS is not fully understood. Early recognition of TTS in these patients is important to guide management and treatment. We present 2 cases of TTS arising in the setting of COVID-19 with rapid progression to biventricular heart failure and cardiogenic shock.

Direct Evidence of Plasticity within Human Primary Motor and Somatosensory Cortices of Patients with Glioblastoma.

Glioblastoma multiforme (GBM) is a devastating disease without cure. It is also the most common primary brain tumor in adults. Although aggressive surgical resection is standard of care, these operations are limited by tumor infiltration of critical cortical and subcortical regions. A better understanding of how the brain can recover and reorganize function in response to GBM would provide valuable clinical data. This ability, termed neuroplasticity, is not well understood in the adult human brain. A better understanding of neuroplasticity in GBM could allow for improved extent of resection, even in areas classically thought to have critical, static function. The best evidence to date has demonstrated neuroplasticity only in slower growing tumors or through indirect measures such as functional MRI or transcranial magnetic stimulation. In this novel study, we utilize a unique experimental paradigm to show direct evidence of plasticity via serial direct electrocortical stimulation (DES) within primary motor (M1) and somatosensory (S1) cortices in GBM patients. Six patients with glioblastoma multiforme in or near the primary motor or somatosensory cortex were included in this retrospective observational study. These patients had two awake craniotomies with DES to map cortical motor and sensory sites in M1 and S1. Five of six patients exhibited at least one site of neuroplasticity within M1 or S1. Out of the 51 total sites stimulated, 32 (62.7%) demonstrated plasticity. Of these sites, 14 (43.7%) were in M1 and 18 (56.3%) were in S1. These data suggest that even in patients with GBM in or near primary brain regions, significant functional reorganization is possible. This is a new finding which may lead to a better understanding of the fundamental factors promoting or inhibiting plasticity. Further exploration may aid in treatment of patients with brain tumors and other neurologic disorders.

Risk Differences in Secondary Prevention Patients Who Present With Acute Coronary Syndrome and Implications of Guideline-Directed Cholesterol Management.

The 2018 American College of Cardiology/American Heart Association cholesterol guidelines for secondary prevention identified a group of "very high risk" (VHR) patients, those with multiple major atherosclerotic cardiovascular disease (ASCVD) events or 1 major ASCVD event with multiple high-risk features. A second group, "high risk" (HR), was defined as patients without any of the risk features in the VHR group. The incidence and relative risk differences of these 2 groups in a nontrial population has not been well characterized. Using the Northwestern Medicine Enterprise Data Warehouse, we compared the incidence of VHR and HR patients as well as their relative risk for cardiovascular morbidity and mortality in a single-center, large, academic, retrospective cohort study. Total 1,483 patients with acute coronary events from January 2014 to December 2016 were risk stratified into VHR and HR groups. International Classification of Diseases versions 9 and 10 were used to assess for composite events of unstable angina pectoris, non-ST elevation myocardial infarction, or ST-elevation myocardial infarction, ischemic stroke, or all-cause death with a median follow-up of 3.3 years. VHR patients were found to have 87 ± 5.4 composite events per 1,000 patient-years compared with HR patients who had 33 ± 5.1 events per 1,000 patient-years (p <0.001). VHR group had increased risk of future events as compared to the HR group (multivariable adjusted hazard ratio 1.66 [1.01 to 2.74], p = 0.047). In conclusion, these results support the stratification of patients into the VHR and HR risk groups for secondary prevention.

Plasticity of the Primary Motor Cortex in Patients with Primary Brain Tumors.

There are two neuron-level mechanisms proposed to underlie neural plasticity: recruiting neurons nearby to support the lost function (ipsilesional plasticity) and uncovering latent pathways that can assume the function that was lost (contralesional plasticity). While both patterns have been demonstrated in patient groups following injury, the specific mechanisms underlying each mode of plasticity are poorly understood. In a retrospective case series of 13 patients, we utilize a novel paradigm that analyzes serial fMRI scans in patients harboring intrinsic brain tumors that vary in location and growth kinetics to better understand the mechanisms underlying these two modes of plasticity in the human primary motor cortex. Twelve patients in our series had some degree of primary motor cortex plasticity, an area previously thought to have limited plasticity. Patients harboring smaller lesions with slower growth kinetics and increasing distance from the primary motor region demonstrated recruitment of ipsilateral motor regions. Conversely, larger, faster-growing lesions in close proximity to the primary motor region were associated with activation of the contralesional primary motor cortex, along with increased activation of the supplementary motor area. These data increase our understanding of the adaptive abilities of the brain and may lead to improved treatment strategies for those suffering from motor loss secondary to brain injuries.

Time-resolved correspondences between deep neural network layers and EEG measurements in object processing.

The ventral visual stream is known to be organized hierarchically, where early visual areas processing simplistic features feed into higher visual areas processing more complex features. Hierarchical convolutional neural networks (CNNs) were largely inspired by this type of brain organization and have been successfully used to model neural responses in different areas of the visual system. In this work, we aim to understand how an instance of these models corresponds to temporal dynamics of human object processing. Using representational similarity analysis (RSA) and various similarity metrics, we compare the model representations with two electroencephalography (EEG) data sets containing responses to a shared set of 72 images. We find that there is a hierarchical relationship between the depth of a layer and the time at which peak correlation with the brain response occurs for certain similarity metrics in both data sets. However, when comparing across layers in the neural network, the correlation onset time did not appear in a strictly hierarchical fashion. We present two additional methods that improve upon the achieved correlations by optimally weighting features from the CNN and show that depending on the similarity metric, deeper layers of the CNN provide a better correspondence than shallow layers to later time points in the EEG responses. However, we do not find that shallow layers provide better correspondences than those of deeper layers to early time points, an observation that violates the hierarchy and is in agreement with the finding from the onset-time analysis. This work makes a first comparison of various response features-including multiple similarity metrics and data sets-with respect to a neural network.

Conditions for reliable grip force and jaw angle estimation of da Vinci surgical tools.

PURPOSE: This work presents an estimation technique as well as corresponding conditions which are necessary to produce an accurate estimate of grip force and jaw angle on a da Vinci surgical tool using back-end sensors alone. METHODS: This work utilizes an artificial neural network as the regression estimator on a dataset acquired from custom hardware on the proximal and distal ends. Through a series of experiments, we test the effect of estimation accuracy due to change in operating frequency, using the opposite jaw, and using different tools. A case study is then presented comparing our estimation technique with direct measurements of material response curves on two synthetic tissue surrogates. RESULTS: We establish the following criteria as necessary to produce an accurate estimate: operate within training frequency bounds, use the same side jaw, and use the same tool. Under these criteria, an average root mean square error of 1.04 mN m in grip force and 0.17 degrees in jaw angle is achieved. Additionally, applying these criteria in the case study resulted in direct measurements which fell within the 95% confidence bands of our estimation technique. CONCLUSION: Our estimation technique, along with important training criteria, is presented herein to further improve the literature pertaining to grip force estimation. We propose the training criteria to begin establishing bounds on the applicability of estimation techniques used for grip force estimation for eventual translation into clinical practice.

Blended shared control utilizing online identification : Regulating grasping forces of a surrogate surgical grasper.

PURPOSE: Surgical robots are increasingly common, yet routine tasks such as tissue grasping remain potentially harmful with high occurrences of tissue crush injury due to the lack of force feedback from the grasper. This work aims to investigate whether a blended shared control framework which utilizes real-time identification of the object being grasped as part of the feedback may help address the prevalence of tissue crush injury in robotic surgeries. METHODS: This work tests the proposed shared control framework and tissue identification algorithm on a custom surrogate surgical robotic grasping setup. This scheme utilizes identification of the object being grasped as part of the feedback to regulate to a desired force. The blended shared control is arbitrated between human and an implicit force controller based on a computed confidence in the identification of the grasped object. The online identification is performed using least squares based on a nonlinear tissue model. Testing was performed on five silicone tissue surrogates. Twenty grasps were conducted, with half of the grasps performed under manual control and half of the grasps performed with the proposed blended shared control, to test the efficacy of the control scheme. RESULTS: The identification method resulted in an average of 95% accuracy across all time samples of all tissue grasps using a full leave-grasp-out cross-validation. There was an average convergence time of [Formula: see text] ms across all training grasps for all tissue surrogates. Additionally, there was a reduction in peak forces induced during grasping for all tissue surrogates when applying blended shared control online. CONCLUSION: The blended shared control using online identification more successfully regulated grasping forces to the desired target force when compared with manual control. The preliminary work on this surrogate setup for surgical grasping merits further investigation on real surgical tools and with real human tissues.

C57BL/6J mouse apolipoprotein A2 gene is deterministic for apnea.

RATIONALE: Brainstem apolipoprotein AII (apoa2) mRNA expression correlates with apnea in breathing present in the adult C57Bl/6J (B6) sleep apnea model. OBJECTIVES: To test the hypothesis that the B6 apoa2 gene contributes to the trait, we performed plethysmographic testing in apoa2 knock out (KO: -/-) mice, an in situ brainstem-spinal cord preparation comparing KO to WT (+/+) mice, and B6xDBA recombinant inbred strains (RISs). MEASUREMENTS AND MAIN RESULTS: Apoa2 WT do, but KO and heterozygote (+/-) mice do not exhibit apnea during post-hypoxic breathing, measured in vivo. In the in situ model, pauses and instability in fictive phrenic bursting are substantially reduced in KO vs. WT preparations. In 24 RISs, apnea number in vivo was higher in strains with B6 apoa2 than with DBA apoa2 alleles. CONCLUSIONS: The B6 apoa2 polymorphism is directly involved in breath production, and its identification suggests a novel pathway influencing risk for adult sleep apnea.