Sex-Based Differences in Severe Outcomes, Including Cardiovascular Hospitalization, in Adults With COVID-19 in Ontario, Canada.

Background: While men have experienced higher risks of SARS-CoV-2 infection compared to women, an analysis of sex differences by age in severe outcomes during the acute phase of infection is lacking. Objectives: The purpose of this study was to assess heterogeneity in severe outcome risks by age and sex by conducting a retrospective cohort study of community-dwelling adults in Ontario who tested positive for SARS-CoV-2 infection during the first 3 waves. Methods: Adjusted odds ratios were estimated using multilevel multivariable logistic regression models including an interaction term for age and sex. The primary outcome was a composite of severe outcomes (hospitalization for a cardiovascular (CV) event, intensive care unit admission, mechanical ventilation, or death) within 30 days. Results: Among 30,736, 199,132, and 186,131 adults who tested positive during the first 3 waves, 1,908 (6.2%), 5,437 (2.7%), and 5,653 (3.0%) experienced a severe outcome within 30 days. For all outcomes, the sex-specific risk depended on age (all P for interaction <0.05). Men with SARS-CoV-2 infection experienced a higher risk of outcomes than infected women of the same age, except for the risk of all-cause hospitalization being higher for young women than men (ages 18-45 years) during waves 2 and 3. The sex disparity in CV hospitalization across all ages either persisted or increased with each subsequent wave. Conclusions: To mitigate risks in subsequent waves, it is helpful to further understand the factors that contribute to the generally higher risks faced by men across all ages, and the persistent or increasing sex disparity in the risk of CV hospitalization.

Association Between Vaccination Status and Outcomes in Patients Admitted to the ICU With COVID-19.

OBJECTIVES: Although COVID-19 vaccines can reduce the need for intensive care unit admission in COVID-19, their effect on outcomes in critical illness remains unclear. We evaluated outcomes in vaccinated patients admitted to the ICU with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the association between vaccination and booster status on clinical outcomes. DESIGN: Retrospective cohort. SETTING AND PATIENTS: All patients were admitted to an ICU between January 2021 (after vaccination was available) and July 2022 with a diagnosis of COVID-19 based on a SARS-CoV-2 polymerase chain reaction test in Alberta, Canada. INTERVENTIONS: None. MEASUREMENT: The propensity-matched primary outcome of all-cause in-hospital mortality was compared between vaccinated and unvaccinated patients, and vaccinated patients were stratified by booster dosing. Secondary outcomes were mechanical ventilation (MV) duration ICU length of stay (LOS). MAIN RESULTS: The study included 3,293 patients: 743 (22.6%) were fully vaccinated (54.6% with booster), 166 (5.0%) were partially vaccinated, and 2,384 (72.4%) were unvaccinated. Unvaccinated patients were more likely to require invasive MV (78.4% vs 68.2%), vasopressor use (71.1% vs 66.6%), and extracorporeal membrane oxygenation (2.1% vs 0.5%). In a propensity-matched analysis, in-hospital mortality was similar (31.8% vs 34.0%, adjusted odds ratio [OR], 1.25; 95% CI, 0.97-1.61), but median duration MV (7.6 vs 4.7 d; p < 0.001) and ICU LOS (6.6 vs 5.2 d; p < 0.001) were longer in unvaccinated compared to fully vaccinated patients. Among vaccinated patients, greater than or equal to 1 booster had lower in-hospital mortality (25.5% vs 40.9%; adjusted OR, 0.50; 95% CI, 0.0.36-0.68) and duration of MV (3.8 vs 5.6 d; p = 0.025). CONCLUSIONS: Nearly one in four patients admitted to the ICU with COVID-19 after widespread COVID-19 vaccine availability represented a vaccine-breakthrough case. Mortality risk remains substantial in vaccinated patients and similar between vaccinated and unvaccinated patients after the onset of critical illness. However, COVID-19 vaccination is associated with reduced ICU resource utilization and booster dosing may increase survivability from COVID-19-related critical illness.

Intrapulmonary and Intracardiac Shunts in Adult COVID-19 Versus Non-COVID Acute Respiratory Distress Syndrome ICU Patients Using Echocardiography and Contrast Bubble Studies (COVID-Shunt Study): A Prospective, Observational Cohort Study.

OBJECTIVES: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 acute respiratory distress syndrome (ARDS) with worse associated outcomes. We evaluated the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia workup for shunt etiology and associations with mortality. DESIGN: Prospective, observational cohort study. SETTING: Four tertiary hospitals in Edmonton, Alberta, Canada. PATIENTS: Adult critically ill, mechanically ventilated, ICU patients admitted with COVID-19 or non-COVID (November 16, 2020, to September 1, 2021). INTERVENTIONS: Agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler ± transesophageal echocardiography assessed for R-L shunts presence. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were shunt frequency and association with hospital mortality. Logistic regression analysis was used for adjustment. The study enrolled 226 patients (182 COVID-19 vs 42 non-COVID). Median age was 58 years (interquartile range [IQR], 47-67 yr) and Acute Physiology and Chronic Health Evaluation II scores of 30 (IQR, 21-36). In COVID-19 patients, the frequency of R-L shunt was 31 of 182 COVID patients (17.0%) versus 10 of 44 non-COVID patients (22.7%), with no difference detected in shunt rates (risk difference [RD], -5.7%; 95% CI, -18.4 to 7.0; p = 0.38). In the COVID-19 group, hospital mortality was higher for those with R-L shunt compared with those without (54.8% vs 35.8%; RD, 19.0%; 95% CI, 0.1-37.9; p = 0.05). This did not persist at 90-day mortality nor after adjustment with regression. CONCLUSIONS: There was no evidence of increased R-L shunt rates in COVID-19 compared with non-COVID controls. R-L shunt was associated with increased in-hospital mortality for COVID-19 patients, but this did not persist at 90-day mortality or after adjusting using logistic regression.

Anticoagulation and Antiplatelet Therapy for Prevention of Venous and Arterial Thrombotic Events in Critically Ill Patients With COVID-19: COVID-PACT.

BACKGROUND: The efficacy and safety of prophylactic full-dose anticoagulation and antiplatelet therapy in critically ill COVID-19 patients remain uncertain. METHODS: COVID-PACT (Prevention of Arteriovenous Thrombotic Events in Critically-ill COVID-19 Patients Trial) was a multicenter, 2×2 factorial, open-label, randomized-controlled trial with blinded end point adjudication in intensive care unit-level patients with COVID-19. Patients were randomly assigned to a strategy of full-dose anticoagulation or standard-dose prophylactic anticoagulation. Absent an indication for antiplatelet therapy, patients were additionally randomly assigned to either clopidogrel or no antiplatelet therapy. The primary efficacy outcome was the hierarchical composite of death attributable to venous or arterial thrombosis, pulmonary embolism, clinically evident deep venous thrombosis, type 1 myocardial infarction, ischemic stroke, systemic embolic event or acute limb ischemia, or clinically silent deep venous thrombosis, through hospital discharge or 28 days. The primary efficacy analyses included an unmatched win ratio and time-to-first event analysis while patients were on treatment. The primary safety outcome was fatal or life-threatening bleeding. The secondary safety outcome was moderate to severe bleeding. Recruitment was stopped early in March 2022 (≈50% planned recruitment) because of waning intensive care unit-level COVID-19 rates. RESULTS: At 34 centers in the United States, 390 patients were randomly assigned between anticoagulation strategies and 292 between antiplatelet strategies (382 and 290 in the on-treatment analyses). At randomization, 99% of patients required advanced respiratory therapy, including 15% requiring invasive mechanical ventilation; 40% required invasive ventilation during hospitalization. Comparing anticoagulation strategies, a greater proportion of wins occurred with full-dose anticoagulation (12.3%) versus standard-dose prophylactic anticoagulation (6.4%; win ratio, 1.95 [95% CI, 1.08-3.55]; P=0.028). Results were consistent in time-to-event analysis for the primary efficacy end point (full-dose versus standard-dose incidence 19/191 [9.9%] versus 29/191 [15.2%]; hazard ratio, 0.56 [95% CI, 0.32-0.99]; P=0.046). The primary safety end point occurred in 4 (2.1%) on full dose and in 1 (0.5%) on standard dose (P=0.19); the secondary safety end point occurred in 15 (7.9%) versus 1 (0.5%; P=0.002). There was no difference in all-cause mortality (hazard ratio, 0.91 [95% CI, 0.56-1.48]; P=0.70). There were no differences in the primary efficacy or safety end points with clopidogrel versus no antiplatelet therapy. CONCLUSIONS: In critically ill patients with COVID-19, full-dose anticoagulation, but not clopidogrel, reduced thrombotic complications with an increase in bleeding, driven primarily by transfusions in hemodynamically stable patients, and no apparent excess in mortality. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04409834.

Clinical risk, sociodemographic factors, and SARS-CoV-2 infection over time in Ontario, Canada.

We aimed to determine whether early public health interventions in 2020 mitigated the association of sociodemographic and clinical risk factors with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We conducted a population-based cohort study of all adults in Ontario, Canada who underwent testing for SARS-CoV-2 through December 31, 2020. The outcome was laboratory-confirmed SARS-CoV-2 infection, determined by reverse transcription polymerase chain reaction testing. Adjusted odds ratios (ORs) were determined for sociodemographic and clinical risk factors before and after the first-wave peak of the pandemic to assess for changes in effect sizes. Among 3,167,753 community-dwelling individuals, 142,814 (4.5%) tested positive. The association between age and SARS-CoV-2 infection risk varied over time (P-interaction < 0.0001). Prior to the first-wave peak, SARS-CoV-2 infection increased with age whereas this association reversed thereafter. Risk factors that persisted included male sex, residing in lower income neighborhoods, residing in more racially/ethnically diverse communities, immigration to Canada, hypertension, and diabetes. While there was a reduction in infection rates after mid-April 2020, there was less impact in regions with higher racial/ethnic diversity. Immediately following the initial peak, individuals living in the most racially/ethnically diverse communities with 2, 3, or ≥ 4 risk factors had ORs of 1.89, 3.07, and 4.73-fold higher for SARS-CoV-2 infection compared to lower risk individuals in their community (all P < 0.0001). In the latter half of 2020, this disparity persisted with corresponding ORs of 1.66, 2.48, and 3.70-fold higher, respectively. In the least racially/ethnically diverse communities, there was little/no gradient in infection rates across risk strata. Further efforts are necessary to reduce the risk of SARS-CoV-2 infection among the highest risk individuals residing in the most racially/ethnically diverse communities.

Derivation and validation of a clinical risk score to predict death among patients awaiting cardiac surgery in Ontario, Canada: a population-based study.

BACKGROUND: Surgical delay may result in unintended harm to patients needing cardiac surgery, who are at risk for death if their condition is left untreated. Our objective was to derive and internally validate a clinical risk score to predict death among patients awaiting major cardiac surgery. METHODS: We used the CorHealth Ontario Registry and linked ICES health administrative databases with information on all Ontario residents to identify patients aged 18 years or more who were referred for isolated coronary artery bypass grafting (CABG), valvular procedures, combined CABG-valvular procedures or thoracic aorta procedures between Oct. 1, 2008, and Sept. 30, 2019. We used a hybrid modelling approach with the random forest method for initial variable selection, followed by backward stepwise logistic regression modelling for clinical interpretability and parsimony. We internally validated the logistic regression model, termed the CardiOttawa Waitlist Mortality Score, using 200 bootstraps. RESULTS: Of the 112 266 patients referred for cardiac surgery, 269 (0.2%) died while awaiting surgery (118/72 366 [0.2%] isolated CABG, 81/24 461 [0.3%] valvular procedures, 63/12 046 [0.5%] combined CABG-valvular procedures and 7/3393 [0.2%] thoracic aorta procedures). Age, sex, surgery type, left main stenosis, Canadian Cardiovascular Society classification, left ventricular ejection fraction, heart failure, atrial fibrillation, dialysis, psychosis and operative priority were predictors of waitlist mortality. The model discriminated (C-statistic 0.76 [optimism-corrected 0.73]). It calibrated well in the overall cohort (Hosmer-Lemeshow p = 0.2) and across surgery types. INTERPRETATION: The CardiOttawa Waitlist Mortality Score is a simple clinical risk model that predicts the likelihood of death while awaiting cardiac surgery. It has the potential to provide data-driven decision support for managing access to cardiac care and preserve system capacity during the COVID-19 pandemic, the recovery period and beyond.

Temporal trends of suicide-related non-traumatic out-of-hospital cardiac arrest characteristics and outcomes with the COVID-19 pandemic.

Background: Jurisdictions have reported COVID-19-related increases in the incidence and mortality of non-traumatic out-of-hospital cardiac arrest (OHCA). We hypothesized that changes in suicide incidence during the COVID-19 pandemic may have contributed to these changes. We investigated whether the COVID-19 pandemic was associated with changes in the: (1) incidence of suicide-related OHCA, and (2) characteristics and outcomes of such cases. Methods: We used the provincial British Columbia Cardiac Arrest Registry, including non-traumatic emergency medical system (EMS)-assessed OHCA, to compare suicide-related OHCA (defined as clear self-harm or a priori communication of intent) one-year prior to, and one year after, the start of the COVID-19 pandemic (March 15, 2020). We calculated differences in incidence (with 95% CI), overall and within subgroups of mechanism (hanging, suffocation, poisoning, or unclear mechanism), and in case characteristics and hospital-discharge favourable neurological outcomes (CPC 1-2). Results: Of 13,785 EMS-assessed OHCA, we included 274/6430 (4.3%) pre-pandemic and 221/7355 (3.0%) pandemic-period suicide-related cases. The median age was 43 years (IQR 30-57), 157 (32%) were female, and 7 (1.4%) survived with favourable neurological status. Suicide-related OHCA incidence decreased from 5.4 pre-pandemic to 4.3 per 100 000 person-years (-1.1, 95% CI -2.0 to -0.28). Hanging-related OHCA incidence also decreased. Patient characteristics and hospital discharge outcomes between periods were similar. Conclusion: Suicide-related OHCA incidence decreased with the COVID-19 pandemic and we did not detect changes in patient characteristics or outcomes, suggesting that suicide is not a contributor to increases in COVID-related OHCA incidence or mortality. Overall suicide-related OHCA outcomes in both time periods were poor.

Statins and SARS-CoV-2 Infection: Results of a Population-Based Prospective Cohort Study of 469 749 Adults From 2 Canadian Provinces.

Background Small observational studies have suggested that statin users have a lower risk of dying with COVID-19. We tested this hypothesis in a large, population-based cohort of adults in 2 of Canada's most populous provinces: Ontario and Alberta. Methods and Results We examined reverse transcriptase-polymerase chain reaction swab positivity rates for SARS-CoV-2 in adults using statins compared with nonusers. In patients with SARS-CoV-2 infection, we compared 30-day risk of all-cause emergency department visit, hospitalization, intensive care unit admission, or death in statin users versus nonusers, adjusting for baseline differences in demographics, clinical comorbidities, and prior health care use, as well as propensity for statin use. Between January and June 2020, 2.4% of 226 142 tested individuals aged 18 to 65 years, 2.7% of 88 387 people aged 66 to 75 years, and 4.1% of 154 950 people older than 75 years had a positive reverse transcriptase-polymerase chain reaction swab for SARS-CoV-2. Compared with 353 878 nonusers, the 115 871 statin users were more likely to test positive for SARS-CoV-2 (3.6% versus 2.8%, P<0.001), but this difference was not significant after adjustment for baseline differences and propensity for statin use in each age stratum (adjusted odds ratio 1.00 [95% CI, 0.88-1.14], 1.00 [0.91-1.09], and 1.06 [0.82-1.38], respectively). In individuals younger than 75 years with SARS-CoV-2 infection, statin users were more likely to visit an emergency department, be hospitalized, be admitted to the intensive care unit, or to die of any cause within 30 days of their positive swab result than nonusers, but none of these associations were significant after multivariable adjustment. In individuals older than 75 years with SARS-CoV-2, statin users were more likely to visit an emergency department (28.2% versus 17.9%, adjusted odds ratio 1.41 [1.23-1.61]) or be hospitalized (32.7% versus 21.9%, adjusted odds ratio 1.19 [1.05-1.36]), but were less likely to die (26.9% versus 31.3%, adjusted odds ratio 0.76 [0.67-0.86]) of any cause within 30 days of their positive swab result than nonusers. Conclusions Compared with statin nonusers, patients taking statins exhibit the same risk of testing positive for SARS-CoV-2 and those younger than 75 years exhibit similar outcomes within 30 days of a positive test. Patients older than 75 years with a positive SARS-CoV-2 test and who were taking statins had more emergency department visits and hospitalizations, but exhibited lower 30-day all-cause mortality risk.

COVID-19 and Disruptive Modifications to Cardiac Critical Care Delivery: JACC Review Topic of the Week.

The COVID-19 pandemic has presented a major unanticipated stress on the workforce, organizational structure, systems of care, and critical resource supplies. To ensure provider safety, to maximize efficiency, and to optimize patient outcomes, health systems need to be agile. Critical care cardiologists may be uniquely positioned to treat the numerous respiratory and cardiovascular complications of the SARS-CoV-2 and support clinicians without critical care training who may be suddenly asked to care for critically ill patients. This review draws upon the experiences of colleagues from heavily impacted regions of the United States and Europe, as well as lessons learned from military mass casualty medicine. This review offers pragmatic suggestions on how to implement scalable models for critical care delivery, cultivate educational tools for team training, and embrace technologies (e.g., telemedicine) to enable effective collaboration despite social distancing imperatives.

The Basics of ARDS Mechanical Ventilatory Care for Cardiovascular Specialists.

The ongoing COVID-19 pandemic has placed pressure on health care systems and intensive care unit capacity worldwide. Respiratory insufficiency is the most common reason for hospital admission in patients with COVID-19. The most severe form of respiratory failure is acute respiratory distress syndrome (ARDS), which is associated with significant morbidity and mortality. Patients with ARDS are often treated with invasive mechanical ventilation according to established evidence-based and guideline recommended management strategies. With growing strain on critical care capacity, clinicians from diverse backgrounds, including cardiovascular specialists, might be required to help care for the growing number of patients with severe respiratory failure and ARDS. The aim of this article is to outline the fundamentals of ARDS diagnosis and management, including mechanical ventilation, for the nonintensivist. In the absence of mechanical ventilation trials specifically in patients with COVID-19-associated ARDS, the information presented is on the basis of general ARDS trials.