Coronavirus Disease 2019–Associated Coagulopathy

Patients with the severe form of coronavirus disease 2019 (COVID-19) have been frequently found to suffer from both arterial and venous thrombotic events due to the perpetuation of a hypercoagulable state. This phenomenon, termed COVID-19–associated coagulopathy, is now considered a major component of the pathophysiology of this novel infectious disease, leading to widespread thrombosis. While at first, the vascular insults may be limited to the pulmonary microvasculature, as the disease progresses, systemic involvement occurs, culminating in distant organ thrombosis and multiorgan dysfunction syndrome. In this review article, we discuss recent insights into the pathophysiologic mechanisms of COVID-19–associated coagulopathy and review the clinical, histopathologic, and laboratory evidence, which leads us to conclude that COVID-19 is both a pulmonary and vascular disorder.     

Prediction of Mortality in Coronary Artery Disease: Role of Machine Learning and Maximal Exercise Capacity

ObjectiveTo develop a prediction model for survival of patients with coronary artery disease (CAD) using health conditions beyond cardiovascular risk factors, including maximal exercise capacity, through the application of machine learning (ML) techniques.MethodsAnalysis of data from a retrospective cohort linking clinical, administrative, and vital status databases from 1995 to 2016 was performed. Inclusion criteria were age 18 years or older, diagnosis of CAD, referral to a cardiac rehabilitation program, and available baseline exercise test results. Primary outcome was death from any cause. Feature selection was performed using supervised and unsupervised ML techniques. The final prognostic model used the survival tree (ST) algorithm.ResultsFrom the cohort of 13,362 patients (60±11 years; 2400 [18%] women), 1577 died during a median follow-up of 8 years (interquartile range, 4 to 13 years), with an estimated survival of 67% up to 21 years. Feature selection revealed age and peak metabolic equivalents (METs) as the features with the greatest importance for mortality prediction. Using these 2 features, the ST generated a long-term prediction with a C-index of 0.729 by splitting patients in 8 clusters with different survival probabilities (P<.001). The ST root node was split by peak METs of 6.15 or less or more than 6.15, and each patient’s subgroup was further split by age or other peak METs cut points.ConclusionApplying ML techniques, age and maximal exercise capacity accurately predict mortality in patients with CAD and outperform variables commonly used for decision-making in clinical practice. A novel and simple prognostic model was established, and maximal exercise capacity was further suggested to be one of the most powerful predictors of mortality in CAD.     

Rates of Severe Outcomes After Bamlanivimab-Etesevimab and Casirivimab-Imdevimab Treatment of High-Risk Patients With Mild to Moderate Coronavirus Disease 2019

Bamlanivimab-etesevimab and casirivimab-imdevimab are authorized by the US Food and Drug Administration for emergency treatment of mild to moderate coronavirus disease 2019 (COVID-19) in high-risk persons. There has been no study comparing their clinical efficacy. In this retrospective study of 681 patients with mild to moderate COVID-19 during a period dominated by severe acute respiratory syndrome coronavirus 2 wild-type and alpha variants, 25 patients (3.7%) had progression to a severe outcome requiring hospitalization and oxygen supplementation within 30 days after monoclonal antibody infusion. Severe outcome was significantly higher among the 181 patients who were treated with casirivimab-imdevimab when compared with the 500 patients who received bamlanivimab-etesevimab (21 [6.6%] vs 13 [2.6%]; P=.01). Patients treated with casirivimab-imdevimab had higher odds of severe outcomes compared with those who received bamlanivimab-etesevimab (odds ratio, 2.67; 95% CI, 1.17 to 6.06). The demographic and clinical characteristics, and the time to monoclonal antibody infusion, of the 2 treatment cohorts were not significantly different. The reason behind this significant difference in the clinical outcomes is unclear, but our observations emphasize potential efficacy differences among antispike monoclonal antibodies against COVID-19. Further clinical studies using larger cohorts of patients are needed to confirm or refute these observations.     

Curbing the Delta Surge: Clinical Outcomes After Treatment With Bamlanivimab-Etesevimab,Casirivimab-Imdevimab,or Sotrovimab for Mild to Moderate Coronavirus Disease 2019

ObjectiveTo describe and compare the clinical outcomes of bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab treatment of mild to moderate coronavirus disease 2019 (COVID-19) during the severe acute respiratory coronavirus 2 (SARS-CoV-2) B.1.617.2 Delta surge.MethodsThis is a retrospective study of high-risk patients who received bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab for mild to moderate COVID-19 between August 1, 2021, and December 1, 2021. Rates of severe disease, hospitalization, intensive care unit admission, and death were assessed.ResultsAmong 10,775 high-risk patients who received bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab for mild to moderate COVID-19 during the Delta surge, 287 patients (2.7%) developed severe disease that led to hospitalization, oxygen supplementation, or death within 30 days after treatment. The rates of severe disease were low among patients treated with bamlanivimab-etesevimab (1.2%), casirivimab-imdevimab (2.9%), and sotrovimab (1.6%; P<.01). The higher rate of severe outcomes among patients treated with casirivimab-imdevimab may be related to a significantly lower COVID-19 vaccination rate in that cohort. Intensive care unit admission was comparable among patients treated bamlanivimab-etesevimab, casirivimab-imdevimab, or sotrovimab (1.0%, 1.0%, and 0.4%, respectively).ConclusionThis real-world study of a large cohort of high-risk patients shows low rates of severe disease, hospitalization, intensive care unit admission, and mortality after treatment with bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab for mild to moderate COVID-19 during the SARS-CoV-2 Delta surge.     

The Oxygen Cascade During Exercise in Health and Disease

The oxygen transport cascade describes the physiological steps that bring atmospheric oxygen into the body where it is delivered and consumed by metabolically active tissue. As such, the oxygen cascade is fundamental to our understanding of exercise in health and disease. Our narrative review will highlight each step of the oxygen transport cascade from inspiration of atmospheric oxygen down to mitochondrial consumption in both healthy active males and females along with clinical conditions. We will focus on how different steps interact along with principles of homeostasis, physiological redundancies, and adaptation. In particular, we highlight some of the parallels between elite athletes and clinical conditions in terms of the oxygen cascade.     

Effectiveness of COVID-19 Booster on the Risk of Hospitalization Among Medicare Beneficiaries

ObjectiveTo determine the effectiveness of booster vaccinations on the risk of hospitalization with coronavirus disease 2019 (COVID-19) and how it varies by enrollee characteristics and interval from the initial vaccination to receipt of a booster.Patients and MethodsThis cohort study used 100% Medicare claims from January 1, 2020, through December 31, 2021, and matched 3,940,475 individuals who received boosters to 3,940,475 controls based on week and type of original COVID-19 vaccine and demographic and clinical characteristics. We compared the association of booster vs no booster with COVID-19 hospitalization using Cox proportional hazards regression models controlling for patient characteristics. We also determined the association of time from original vaccine to booster with COVID-19 hospitalization.ResultsOver a maximum of 130 days of follow-up, boosted enrollees had 8.20 (95% CI, 7.81 to 8.60) COVID-19 hospitalizations per million days vs 43.70 (95% CI, 42.79 to 44.64) for controls (81% effectiveness). Effectiveness varied by race, prior hospitalizations, and certain comorbidities, for example, leukemia/lymphoma (53% effectiveness), autoimmune disease (73%), and dementia (73%). Boosters received between 6 and 9 months after original vaccination varied between 81% and 85% effectiveness, while boosters received at 5 to 6 months (62%) or less than 5 months (58%) were less effective.ConclusionBoosters are highly effective in the Medicare population. Approximately 69,225 hospitalizations would be prevented by boosters in the 15 million individuals aged 65 years or older currently not boosted in a period similar to the September 2020 through January 2021 period studied. Boosters provided the greatest benefits if they were received between 6 and 9 months following original vaccinations. However, boosters were associated with substantial decreases in COVID-19 hospitalizations in all categories of enrollees.     

Synergistic Assessment of Mortality Risk According to Body Mass Index and Exercise Ability and Capacity in Patients Referred for Radionuclide Stress Testing

ObjectiveTo determine the interrelationship between body mass index (BMI), mode of stress testing (exercise or pharmacological), exercise capacity, and all-cause mortality in patients referred for stress-rest single photon emission computed tomography myocardial perfusion imaging.Patients and MethodsWe evaluated all-cause mortality in 21,638 patients undergoing stress-rest single photon emission computed tomography myocardial perfusion imaging between January 2, 1991, and December 31, 2012. Patients were divided into exercise and pharmacologically tested groups and 9 BMI categories. The median follow-up was 12.8 years (range, 5.0-26.8 years).ResultsIn exercise patients, mortality was increased with both low and high BMI vs patients with a normal referent BMI of 22.5 to 24.9 kg/m². In pharmacologically tested patients, only low BMI, but not high BMI, was associated with increased mortality vs normal BMI. When exercise and pharmacologically tested groups were compared directly, pharmacologically tested patients manifested a marked increase in mortality risk vs exercise patients within each BMI category, ranging from an approximately 4-fold increase in mortality in those with normal or high BMI to a 12.3-fold increase in those with low BMI values. Similar findings were observed in a cohort of 4804 exercise and 4804 pharmacologically tested patients matched to have similar age and coronary artery disease risk factor profiles. In exercise patients, further risk stratification was achieved when considering both BMI and metabolic equivalent tasks of achieved exercise.ConclusionThe combined assessment of BMI and exercise ability and capacity provides synergistic and marked risk stratification of future mortality risk in patients referred for radionuclide stress testing, providing considerable insights into the “obesity paradox” that is observed in populations referred for stress testing.     

Exercise Counteracts the Cardiotoxicity of Psychosocial Stress

Physical inactivity and psychosocial stress are prevalent in residents of the United States. The purpose of this article is to review the interaction between these 2 conditions and examine the effects of exercise on stress and cardiovascular (CV) health. A query of scientific references between 1974 to 2018 was performed using the PubMed search engine accessing the MEDLINE database using the search terms psychosocial stress, CV disease (CVD), physical activity, exercise, cardiac rehabilitation, and team sports. Psychosocial stress is a strong independent risk factor for adverse CV events. Conversely, people who experience CV events subsequently have drastically elevated rates of new-onset mental health disorders, including depression and anxiety. Psychosocial stress and CVD often trigger self-reinforcing feedback loops that can worsen mental health and cardiac prognosis. Exercise predictably improves CV health and prognosis and also is effective at lowering levels of psychosocial stress. Group exercise in particular seems to provide social support while at the same time boosting fitness levels and, thus, may be the single most important intervention for patients with concomitant CVD and emotional stress. Collaborative physical activity, such as group exercise, team sports, interactive physical play, and cardiac rehabilitation programs, have the potential to improve mental health and CV prognosis.