Major adverse cardiovascular events (MACE) in patients with severe COVID-19 registered in the ISARIC WHO clinical characterization protocol: A prospective, multinational, observational study.

PURPOSE: To determine its cumulative incidence, identify the risk factors associated with Major Adverse Cardiovascular Events (MACE) development, and its impact clinical outcomes. MATERIALS AND METHODS: This multinational, multicentre, prospective cohort study from the ISARIC database. We used bivariate and multivariate logistic regressions to explore the risk factors related to MACE development and determine its impact on 28-day and 90-day mortality. RESULTS: 49,479 patients were included. Most were male 63.5% (31,441/49,479) and from high-income countries (84.4% [42,774/49,479]); however, >6000 patients were registered in low-and-middle-income countries. MACE cumulative incidence during their hospital stay was 17.8% (8829/49,479). The main risk factors independently associated with the development of MACE were older age, chronic kidney disease or cardiovascular disease, smoking history, and requirement of vasopressors or invasive mechanical ventilation at admission. The overall 28-day and 90-day mortality were higher among patients who developed MACE than those who did not (63.1% [5573/8829] vs. 35.6% [14,487/40,650] p < 0.001; 69.9% [6169/8829] vs. 37.8% [15,372/40,650] p < 0.001, respectively). After adjusting for confounders, MACE remained independently associated with higher 28-day and 90-day mortality (Odds Ratio [95% CI], 1.36 [1.33-1.39];1.47 [1.43-1.50], respectively). CONCLUSIONS: Patients with severe COVID-19 frequently develop MACE, which is independently associated with worse clinical outcomes.

Positioning of tofacitinib in treatment of ulcerative colitis: a global perspective.

INTRODUCTION: Tofacitinib has emerged as a useful drug for the treatment of ulcerative colitis (UC). AREAS COVERED: There is an unmet need for cost-effective, non-immunogenic drugs with a safe adverse effect profile to treat patients with ulcerative colitis. In the present review, we evaluate the available literature to inform the appropriate positioning of tofacitinib in the current drug landscape and identify subsets where its use should be done with caution. EXPERT OPINION: Tofacitinib is helpful in the treatment of patients where the standard conventional or biological therapies have failed or were not tolerated. With lower costs of the generic drug than the biologicals (or biosimilars), it could be an important therapy in low- to middle-income countries. The risk of infections, especially Herpes Zoster and tuberculosis, needs to be addressed before initiation. Tofacitinib should be avoided in patients with venous thromboembolism and cardiovascular disease risk factors. Due to limited evidence, the use is not recommended in pregnancy, while it should be used with caution in elderly citizens. Future trials should look into the head-to-head comparison of tofacitinib with biologicals. The role of tofacitinib in acute severe colitis needs evaluation with comparative trials with current standards of care.

Atrial fibrillation is a risk factor for major adverse cardiovascular events in COVID-19.

Background: New-onset atrial fibrillation (AF) during COVID-19 infection is associated with worse cardiovascular outcomes and mortality, with new-onset AF being associated with worse clinical outcomes than recurrent AF. However, it is not known whether a prior history of AF is an independent cardiovascular risk factor predicting worse outcomes in COVID-19 patients. The present investigation sought to determine whether AF should be considered a risk factor for worse outcomes in COVID-19 illness. Methods: From March 2020-September 2021 patients testing positive for SARS-CoV-2 with a prior AF diagnosis (n = 3623) were propensity matched to non-AF SARS-CoV-2 positive patients (n = 3610). Multivariable Cox hazard regression was used to determine subsequent MACE (all-cause death, myocardial infarction, HF and stroke) risk among patients with and without AF. Results: COVID-19 patients with a prior history of AF were more likely to be hospitalized, require ICU care, supplemental oxygen, and ventilator support compared COVID-19 patients without a history of AF. There was a 1.40 times higher rate of MACE in the COVID-19 patients with prior AF compared to patients without prior AF (p < 0.0001). The increased rate of MACE in patients with a prior AF was primarily secondary to increases in heart failure hospitalization and death. This finding was confirmed even after controlling for acute AF during COVID-19 illness (HR 1.22, p = 0.0009). Conclusion: AF history was shown to be an independent risk factor for MACE during a COVID-19 illness. Both recurrent and principally new-onset AF were associated with an increased risk of poor clinical outcomes during COVID-19 illness.

Clinical outcomes of COVID-19 infection in patients with pre-existing cardiovascular disease.

Introduction: Patients with pre-existing cardiovascular disease may carry a higher risk for mortality from COVID-19. This study examined the association between individuals with pre-existing cardiovascular disease admitted for COVID-19 and their clinical outcomes. Methods: A retrospective cohort study was conducted on patients admitted with COVID-19 to Rush University System for Health (RUSH) to identify cardiovascular risk factors associated with increased mortality and major adverse cardiovascular events (MACE; a composite of cardiovascular death, stroke, myocardial injury, and heart failure exacerbation). Multivariable logistic regression was used to adjust for demographic data and comorbid conditions. Results: Of the 1682 patients who met inclusion criteria, the median age was 59. Patients were predominantly African American (34.4 %) and male (54.5 %). Overall, 202 (12 %) patients suffered 60-day mortality. In the multivariable model that assessed risk factors for 60-day mortality, age 60-74 (adjusted odds ratio [aOR] 3.30 [CI: 1.23-10.62]; p < 0.05) and age 75-100 (aOR 4.52 [CI: 1.46-16.15]; p < 0.05) were significant predictors when compared to those aged 19 to 39. This model also showed that those with past medical histories of atrial fibrillation (aOR 2.47 [CI: 1.38-4.38]; p < 0.01) and venous thromboembolism (aOR 2.00 [CI: 1.12-3.50]; p < 0.05) were at higher risk of 60-day mortality. Conclusion: In this cohort, patients over 60 years old with a pre-existing history of atrial fibrillation and venous thromboembolism were at increased risk of mortality from COVID-19.

Association between BNT162b2 or CoronaVac COVID-19 vaccines and major adverse cardiovascular events among individuals with cardiovascular disease.

AIMS: Concern about the cardiovascular safety of coronavirus disease 2019 (COVID-19) vaccines among individuals with cardiovascular disease (CVD) may lead to vaccine hesitancy. We sought to assess the association between two COVID-19 vaccines, BNT162b2 and CoronaVac, and the risk of major adverse cardiovascular events (MACE) in individuals with established CVD. METHODS AND RESULTS: We identified individuals with a history of CVD before 23 February 2021 and a diagnosis of MACE between 23 February 2021 and 31 January 2022 in Hong Kong. MACE was defined as a composite of myocardial infarction, stroke, revascularization, and cardiovascular death. Electronic health records from the Hong Kong Hospital Authority were linked to vaccination records from the Department of Health. A self-controlled case-series method was used to evaluate the risk of MACE for 0-13 and 14-27 days after two doses of COVID-19 vaccine. We estimated incidence rate ratios (IRRs) to compare the risk of MACE between each risk period and the baseline period. A total of 229 235 individuals with CVD were identified, of which 1764 were vaccinated and had a diagnosis of MACE during the observation period (BNT162b2 = 662; CoronaVac = 1102). For BNT162b2, IRRs were 0.48 [95% confidence interval (CI) 0.23-1.02] for the first dose and 0.87 (95% CI 0.50-1.52) for the second dose during the 0-13 days risk period, 0.40 (95% CI 0.18-0.93) for the first dose and 1.13 (95% CI 0.70-1.84) for the second dose during the 14-27 days risk period. For CoronaVac, the IRRs were 0.43 (95% CI 0.24-0.75) for the first dose and, 0.73 (95% CI 0.46-1.16) for the second dose during the 0-13 days risk period, 0.54 (95% CI 0.33-0.90) for the first dose and 0.83 (95% CI 0.54-1.29) for the second dose during the 14-27 days risk period. Consistent results were found in subgroup analyses for different sexes, age groups and different underlying cardiovascular conditions. CONCLUSION: Our findings showed no evidence of an increased risk of MACE after vaccination with BNT162b2 or CoronaVac in patients with CVD. Future research is required to monitor the risk after the third dose of each vaccine.

Hyperdynamic left ventricular ejection fraction is associated with higher mortality in COVID-19 patients.

Study objective: To compare the characteristics and outcomes of COVID-19 patients with a hyperdynamic LVEF (HDLVEF) to those with a normal or reduced LVEF. Design: Retrospective study. Setting: Rush University Medical Center. Participants: Of the 1682 adult patients hospitalized with COVID-19, 419 had a transthoracic echocardiogram (TTE) during admission and met study inclusion criteria. Interventions: Participants were divided into reduced (LVEF < 50%), normal (≥50% and <70%), and hyperdynamic (≥70%) LVEF groups. Main outcome measures: LVEF was assessed as a predictor of 60-day mortality. Logistic regression was used to adjust for age and BMI. Results: There was no difference in 60-day mortality between patients in the reduced LVEF and normal LVEF groups (adjusted odds ratio [aOR] 0.87, p = 0.68). However, patients with an HDLVEF were more likely to die by 60 days compared to patients in the normal LVEF group (aOR 2.63 [CI: 1.36-5.05]; p < 0.01). The HDLVEF group was also at higher risk for 60-day mortality than the reduced LVEF group (aOR 3.34 [CI: 1.39-8.42]; p < 0.01). Conclusion: The presence of hyperdynamic LVEF during a COVID-19 hospitalization was associated with an increased risk of 60-day mortality, the requirement for mechanical ventilation, vasopressors, and intensive care unit.

Prognostic Value of Machine Learning in Patients with Acute Myocardial Infarction.

(1) Background: Patients with acute myocardial infarction (AMI) still experience many major adverse cardiovascular events (MACEs), including myocardial infarction, heart failure, kidney failure, coronary events, cerebrovascular events, and death. This retrospective study aims to assess the prognostic value of machine learning (ML) for the prediction of MACEs. (2) Methods: Five-hundred patients diagnosed with AMI and who had undergone successful percutaneous coronary intervention were included in the study. Logistic regression (LR) analysis was used to assess the relevance of MACEs and 24 selected clinical variables. Six ML models were developed with five-fold cross-validation in the training dataset and their ability to predict MACEs was compared to LR with the testing dataset. (3) Results: The MACE rate was calculated as 30.6% after a mean follow-up of 1.42 years. Killip classification (Killip IV vs. I class, odds ratio 4.386, 95% confidence interval 1.943-9.904), drug compliance (irregular vs. regular compliance, 3.06, 1.721-5.438), age (per year, 1.025, 1.006-1.044), and creatinine (1 µmol/L, 1.007, 1.002-1.012) and cholesterol levels (1 mmol/L, 0.708, 0.556-0.903) were independent predictors of MACEs. In the training dataset, the best performing model was the random forest (RDF) model with an area under the curve of (0.749, 0.644-0.853) and accuracy of (0.734, 0.647-0.820). In the testing dataset, the RDF showed the most significant survival difference (log-rank p = 0.017) in distinguishing patients with and without MACEs. (4) Conclusions: The RDF model has been identified as superior to other models for MACE prediction in this study. ML methods can be promising for improving optimal predictor selection and clinical outcomes in patients with AMI.

Additional Value of Non-contrast Chest CT in the Prediction of Adverse Cardiovascular Events in Patients With Novel Coronavirus Disease 2019 (COVID-19).

Background: Coronavirus disease 2019 (COVID-19) has outbroken in China and subsequently spread worldwide since the end of 2019. Chest computed tomography (CT) plays an important role in the diagnosis of lung diseases, but its value in the diagnosis of cardiac injury remains unknown. Methods: We enrolled 241 consecutive hospitalized patients (aged 61 ± 16 years, 115 males) with laboratory-confirmed COVID-19 at Renmin Hospital of Wuhan University from January 11 to March 2, 2020. They were divided into two groups according to whether major adverse cardiovascular events (MACEs) occurred during the follow-up. The anteroposterior diameter of the left atrium (LAD), the length of the left ventricle (LV), and cardiothoracic ratio (CTR) were measured. The values of myocardial CT were also recorded. Results: Of 241 patients, 115 patients (47.7%) had adverse cardiovascular events. Compared with no MACEs, patients with MACEs were more likely to have bilateral lesions (95.7% vs. 86.5%, p = 0.01). In multivariable analysis, bronchial wall thickening would increase the odds of MACEs by 13.42 (p = 0.01). LAD + LV and CTR was the best predictor for MACEs (area under the curve = 0.88, p < 0.001) with a sensitivity of 82.6% and a specificity of 80.2%. Plasma high-sensitivity troponin I levels in patients with cardiac injury showed a moderate negative correlation with minimum CT value (R 2 = -0.636, p < 0.001). Conclusions: Non-contrast chest CT can be a useful modality for detection cardiac injury and provide additional value to predict MACEs in COVID-19 patients.

Cardiovascular findings on chest computed tomography associated with COVID-19 adverse clinical outcomes.

STUDY OBJECTIVE: Chest computed tomography (chest CT) is routinely obtained to assess disease severity in COVID-19. While pulmonary findings are well-described in COVID-19, the implications of cardiovascular findings are less well understood. We evaluated the impact of cardiovascular findings on chest CT on the adverse composite outcome (ACO) of hospitalized COVID-19 patients. SETTING/PARTICIPANTS: 245 COVID-19 patients who underwent chest CT at Rush University Health System were included. DESIGN: Cardiovascular findings, including coronary artery calcification (CAC), aortic calcification, signs of right ventricular strain [right ventricular to left ventricular diameter ratio, pulmonary artery to aorta diameter ratio, interventricular septal position, and inferior vena cava (IVC) reflux], were measured by trained physicians. INTERVENTIONS/MAIN OUTCOME MEASURES: These findings, along with pulmonary findings, were analyzed using univariable logistic analysis to determine the risk of ACO defined as intensive care admission, need for non-invasive positive pressure ventilation, intubation, in-hospital and 60-day mortality. Secondary endpoints included individual components of the ACO. RESULTS: Aortic calcification was independently associated with an increased risk of the ACO (odds ratio 1.86, 95% confidence interval (1.11-3.17) p < 0.05). Aortic calcification, CAC, abnormal septal position, or IVC reflux of contrast were all significantly associated with 60-day mortality and major adverse cardiovascular events. IVC reflux was associated with in-hospital mortality (p = 0.005). CONCLUSION: Incidental cardiovascular findings on chest CT are clinically important imaging markers in COVID-19. It is important to ascertain and routinely report cardiovascular findings on CT imaging of COVID-19 patients as they have potential to identify high risk patients.