Background: The COVID-19 pandemic has exposed longstanding racial/ethnic inequities in health risks and outcomes in the U.S.. We sought to identify racial/ethnic differences in presentation and outcomes for patients hospitalized with COVID-19. Methods: The American Heart Association COVID-19 Cardiovascular Disease Registry is a retrospective observational registry capturing consecutive patients hospitalized with COVID-19. We present data on the first 7,868 patients by race/ethnicity treated at 88 hospitals across the US between 01/17/2020 and 7/22/2020. The primary outcome was in-hospital mortality; secondary outcomes included major adverse cardiovascular events (MACE: death, myocardial infarction, stroke, heart failure) and COVID-19 cardiorespiratory ordinal severity score (worst to best: death, cardiac arrest, mechanical ventilation with mechanical circulatory support, mechanical ventilation with vasopressors/inotrope support, mechanical ventilation without hemodynamic support, and hospitalization without any of the above). Multivariable logistic regression analyses were performed to assess the relationship between race/ethnicity and each outcome adjusting for differences in sociodemographic, clinical, and presentation features, and accounting for clustering by hospital. Results: Among 7,868 patients hospitalized with COVID-19, 33.0% were Hispanic, 25.5% were non-Hispanic Black, 6.3% were Asian, and 35.2% were non-Hispanic White. Hispanic and Black patients were younger than non-Hispanic White and Asian patients and were more likely to be uninsured. Black patients had the highest prevalence of obesity, hypertension, and diabetes. Black patients also had the highest rates of mechanical ventilation (23.2%) and renal replacement therapy (6.6%) but the lowest rates of remdesivir use (6.1%). Overall mortality was 18.4% with 53% of all deaths occurring in Black and Hispanic patients. The adjusted odds ratios (ORs) for mortality were 0.93 (95% confidence interval [CI] 0.76-1.14) for Black patients, 0.90 (95% CI 0.73-1.11) for Hispanic patients, and 1.31 (95% CI 0.96-1.80) for Asian patients compared with non-Hispanic White patients. The median OR across hospitals was 1.99 (95% CI 1.74-2.48). Results were similar for MACE. Asian patients had the highest COVID-19 cardiorespiratory severity at presentation (adjusted OR 1.48, 95% CI 1.16-1.90). Conclusions: Although in-hospital mortality and MACE did not differ by race/ethnicity after adjustment, Black and Hispanic patients bore a greater burden of mortality and morbidity due to their disproportionate representation among COVID-19 hospitalizations.

Propensity score weighting methods are often used in non-randomized studies to adjust for confounding and assess treatment effects. The most popular among them, the inverse probability weighting, assigns weights that are proportional to the inverse of the conditional probability of a specific treatment assignment, given observed covariates. A key requirement for inverse probability weighting estimation is the positivity assumption, i.e. the propensity score must be bounded away from 0 and 1. In practice, violations of the positivity assumption often manifest by the presence of limited overlap in the propensity score distributions between treatment groups. When these practical violations occur, a small number of highly influential inverse probability weights may lead to unstable inverse probability weighting estimators, with biased estimates and large variances. To mitigate these issues, a number of alternative methods have been proposed, including inverse probability weighting trimming, overlap weights, matching weights, and entropy weights. Because overlap weights, matching weights, and entropy weights target the population for whom there is equipoise (and with adequate overlap) and their estimands depend on the true propensity score, a common criticism is that these estimators may be more sensitive to misspecifications of the propensity score model. In this paper, we conduct extensive simulation studies to compare the performances of inverse probability weighting and inverse probability weighting trimming against those of overlap weights, matching weights, and entropy weights under limited overlap and misspecified propensity score models. Across the wide range of scenarios we considered, overlap weights, matching weights, and entropy weights consistently outperform inverse probability weighting in terms of bias, root mean squared error, and coverage probability.

Background—: Surgical risk scores do not include frailty assessments (eg, gait speed), which are of particular importance for patients with severe aortic stenosis considering transcatheter aortic valve replacement. Methods and Results—: We assessed the association of 5-m gait speed with outcomes in a cohort of 8039 patients who underwent transcatheter aortic valve replacement (November 2011–June 2014) and were included in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. We evaluated the association between continuous and categorical gait speed and 30-day all-cause mortality before and after adjustment for Society of Thoracic Surgeons–predicted risk of mortality score and key variables. Secondary outcomes included in-hospital mortality, bleeding, acute kidney injury, and stroke. The overall median gait speed was 0.63 m/s (25th–75th percentile, 0.47–0.79 m/s), with the slowest walkers (0.83 m/s) constituting 24% of the population. Thirty-day all-cause mortality rates were 8.4%, 6.6%, and 5.4% for the slowest, slow, and normal walkers, respectively ( P <0.001). Each 0.2-m/s decrease in gait speed corresponded to an 11% increase in 30-day mortality (adjusted odds ratio, 1.11; 95% confidence interval, 1.01–1.22). The slowest walkers had 35% higher 30-day mortality than normal walkers (adjusted odds ratio, 1.35; 95% confidence interval, 1.01–1.80), significantly longer hospital stays, and a lower probability of being discharged to home. Conclusions—: Gait speed is independently associated with 30-day mortality after transcatheter aortic valve replacement. Identification of frail patients with the slowest gait speeds facilitates preprocedural evaluation and anticipation of a higher level of postprocedural care. Clinical Trial Registration—: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01737528.

Amyloid β (Aβ) peptides, the main pathological species associated with Alzheimer's disease (AD), disturb intracellular calcium homeostasis, which in turn activates the calcium-dependent phosphatase calcineurin (CaN). CaN activation induced by Aβ leads to pathological morphological changes in neurons, and overexpression of constitutively active calcineurin is sufficient to generate a similar phenotype, even without Aβ. Here, we tested the hypothesis that calcineurin mediates neurodegenerative effects via activation of the nuclear transcription factor of activated T-cells (NFAT). We found that both spine loss and dendritic branching simplification induced by Aβ exposure were mimicked by constitutively active NFAT, and abolished when NFAT activation was blocked using the genetically encoded inhibitor VIVIT. When VIVIT was specifically addressed to the nucleus, identical beneficial effects were observed, thus enforcing the role of NFAT transcriptional activity in Aβ-related neurotoxicity.In vivo, when VIVIT or its nuclear counterpart were overexpressed in a transgenic model of Alzheimer's disease via a gene therapy approach, the spine loss and neuritic abnormalities observed in the vicinity of amyloid plaques were blocked. Overall, these results suggest that NFAT/calcineurin transcriptional cascades contribute to Aβ synaptotoxicity, and may provide a new specific set of pathways for neuroprotective strategies.

Background: Catheter ablation is an increasingly used treatment for symptomatic atrial fibrillation (AF). However, there are limited prospective, nationwide data on patient selection and procedural characteristics. This study describes patient characteristics, techniques, treatment patterns, and safety outcomes of patients undergoing AF ablation. Methods: A total of 3139 patients undergoing AF ablation between 2016 and 2018 in the Get With The Guidelines-Atrial Fibrillation registry from 24 US centers were included. Patient demographics, medical history, procedural details, and complications were abstracted. Differences between paroxysmal and patients with persistent AF were compared using Pearson χ ² and Wilcoxon rank-sum tests. Results: Patients undergoing AF ablation were predominantly male (63.9%) and White (93.2%) with a median age of 65. Hypertension was the most common comorbidity (67.6%), and patients with persistent AF had more comorbidities than patients with paroxysmal AF. Drug refractory, paroxysmal AF was the most common ablation indication (class I, 53.6%) followed by drug refractory, persistent AF (class I, 41.8%). Radiofrequency ablation with contact force sensing was the most common ablation modality (70.5%); 23.7% of patients underwent cryoballoon ablation. Pulmonary vein isolation was performed in 94.6% of de novo ablations; the most common adjunctive lesions included left atrial roof or posterior/inferior lines, and cavotricuspid isthmus ablation. Complications were uncommon (5.1%) and were life-threatening in 0.7% of cases. Conclusions: More than 98% of AF ablations among participating sites are performed for class I or class IIA indications. Contact force-guided radiofrequency ablation is the dominant technique and pulmonary vein isolation the principal lesion set. In-hospital complications are uncommon and rarely life-threatening.