Specific characteristics of STEMI in COVID-19 patients and their practical implications.

ST-elevation myocardial infarction (STEMI) is one of the cardiac emergencies whose management has been most challenged by the COVID-19 pandemic. Patients presenting with the "lethal combo" of STEMI and concomitant SARS-CoV-2 infection have faced dramatic issues related to the need for self-isolation, systemic inflammation with multi-organ disease and difficulties to obtain timely diagnosis and treatment. The interplay between these and other factors has partly neutralized the major advances in STEMI care achieved in the last decades, significantly impairing prognosis in these patients. In the present review article, we will provide an overview on mechanisms of myocardial injury, specific clinical and angiographic characteristics and contemporary management in different settings of STEMI patients with COVID-19, alongside the inherent implications in terms of in-hospital mortality and short-term clinical outcomes.

Immunologic Dysregulation and Hypercoagulability as a Pathophysiologic Background in COVID-19 Infection and the Immunomodulating Role of Colchicine.

In 2020, SARS-COV-2 put health systems under unprecedented resource and manpower pressure leading to significant number of deaths. Expectedly, researchers sought to shed light on the pathophysiologic background of this novel disease (COVID-19) as well as to facilitate the design of effective therapeutic modalities. Indeed, early enough the pivotal role of inflammatory and thrombotic pathways in SARS-COV-2 infection has been illustrated. The purpose of this article is to briefly present the epidemiologic and clinical features of COVID-19, analyze the pathophysiologic importance of immunologic dysregulation and hypercoagulability in developing disease complications and finally to present an up-to-date systematic review of colchicine's immunomodulating capacity in view of hindering coronavirus complications.

Repurposing colchicine's journey in view of drug-to-drug interactions. A review.

Colchicine's medical evolution is historically bound to the Mediterranean basin, since remarkable researchers from this region underscored its valuable properties. With the passing of years colchicine became an essential pharmaceutical substance for the treatment of rheumatologic and cardiovascular diseases. In light of recent findings, the therapeutic value of colchicine has grown. In clinical practice, colchicine remains underutilized in view of its proven efficacy and safety. Its complex pharmacokinetics and multifaceted anti-inflammatory role remain under investigation. The current review addresses the safe administration of colchicine in view of key drug to drug interactions. Finally, we are briefly presenting colchicine's future potential applications.

Early detection of elevated cardiac biomarkers to optimise risk stratification in patients with COVID-19.

OBJECTIVE: Risk stratification is crucial to optimise treatment strategies in patients with COVID-19. We aimed to evaluate the impact on mortality of an early assessment of cardiac biomarkers in patients with COVID-19. METHODS: Humanitas Clinical and Research Hospital (Rozzano-Milan, Lombardy, Italy) is a tertiary centre that has been converted to the management of COVID-19. Patients with confirmed COVID-19 were entered in a dedicated database for cohort observational analyses. Outcomes were stratified according to elevated levels (ie, above the upper level of normal) of high-sensitivity cardiac troponin I (hs-TnI), B-type natriuretic peptide (BNP) or both measured within 24 hours after hospital admission. The primary outcome was all-cause mortality. RESULTS: A total of 397 consecutive patients with COVID-19 were included up to 1 April 2020. At the time of hospital admission, 208 patients (52.4%) had normal values for cardiac biomarkers, 90 (22.7%) had elevated both hs-TnI and BNP, 59 (14.9%) had elevated only BNP and 40 (10.1%) had elevated only hs-TnI. The rate of mortality was higher in patients with elevated hs-TnI (22.5%, OR 4.35, 95% CI 1.72 to 11.04), BNP (33.9%, OR 7.37, 95% CI 3.53 to 16.75) or both (55.6%, OR 18.75, 95% CI 9.32 to 37.71) as compared with those without elevated cardiac biomarkers (6.25%). A multivariate analysis identified concomitant elevation of both hs-TnI and BNP as a strong independent predictor of all-cause mortality (OR 3.24, 95% CI 1.06 to 9.93). CONCLUSIONS: An early detection of elevated hs-TnI and BNP predicts mortality in patients with COVID-19. Cardiac biomarkers should be systematically assessed in patients with COVID-19 at the time of hospital admission in order to optimise risk stratification.

Risk factors for myocardial injury and death in patients with COVID-19: insights from a cohort study with chest computed tomography.

AIMS: Whether pulmonary artery (PA) dimension and coronary artery calcium (CAC) score, as assessed by chest computed tomography (CT), are associated with myocardial injury in patients with coronavirus disease 2019 (COVID-19) is not known. The aim of this study was to explore the risk factors for myocardial injury and death and to investigate whether myocardial injury has an independent association with all-cause mortality in patients with COVID-19. METHODS AND RESULTS: This is a single-centre cohort study including consecutive patients with laboratory-confirmed COVID-19 undergoing chest CT on admission. Myocardial injury was defined as high-sensitivity troponin I >20 ng/L on admission. A total of 332 patients with a median follow-up of 12 days were included. There were 68 (20.5%) deaths; 123 (37%) patients had myocardial injury. PA diameter was higher in patients with myocardial injury compared with patients without myocardial injury [29.0 (25th-75th percentile, 27-32) mm vs. 27.7 (25-30) mm, P < 0.001). PA diameter was independently associated with an increased risk of myocardial injury [adjusted odds ratio 1.10, 95% confidence interval (CI) 1.02-1.19, P = 0.01] and death [adjusted hazard ratio (HR) 1.09, 95% CI 1.02-1.17, P = 0.01]. Compared with patients without myocardial injury, patients with myocardial injury had a lower prevalence of a CAC score of zero (25% vs. 55%, P < 0.001); however, the CAC score did not emerge as a predictor of myocardial injury by multivariable logistic regression. Myocardial injury was independently associated with an increased risk of death by multivariable Cox regression (adjusted HR 2.25, 95% CI 1.27-3.96, P = 0.005). Older age, lower estimated glomerular filtration rate, and lower PaO2/FiO2 ratio on admission were other independent predictors for both myocardial injury and death. CONCLUSIONS: An increased PA diameter, as assessed by chest CT, is an independent risk factor for myocardial injury and mortality in patients with COVID-19. Myocardial injury is independently associated with an approximately two-fold increased risk of death.

Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial.

Importance: Severe acute respiratory syndrome coronavirus 2 infection has evolved into a global pandemic. Low-dose colchicine combines anti-inflammatory action with a favorable safety profile. Objective: To evaluate the effect of treatment with colchicine on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19). Design, Setting, and Participants: In this prospective, open-label, randomized clinical trial (the Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention), 105 patients hospitalized with COVID-19 were randomized in a 1:1 allocation from April 3 to April 27, 2020, to either standard medical treatment or colchicine with standard medical treatment. The study took place in 16 tertiary hospitals in Greece. Intervention: Colchicine administration (1.5-mg loading dose followed by 0.5 mg after 60 min and maintenance doses of 0.5 mg twice daily) with standard medical treatment for as long as 3 weeks. Main Outcomes and Measures: Primary end points were (1) maximum high-sensitivity cardiac troponin level; (2) time for C-reactive protein to reach more than 3 times the upper reference limit; and (3) time to deterioration by 2 points on a 7-grade clinical status scale, ranging from able to resume normal activities to death. Secondary end points were (1) the percentage of participants requiring mechanical ventilation, (2) all-cause mortality, and (3) number, type, severity, and seriousness of adverse events. The primary efficacy analysis was performed on an intention-to-treat basis. Results: A total of 105 patients were evaluated (61 [58.1%] men; median [interquartile range] age, 64 [54-76] years) with 50 (47.6%) randomized to the control group and 55 (52.4%) to the colchicine group. Median (interquartile range) peak high-sensitivity cardiac troponin values were 0.0112 (0.0043-0.0093) ng/mL in the control group and 0.008 (0.004-0.0135) ng/mL in the colchicine group (P = .34). Median (interquartile range) maximum C-reactive protein levels were 4.5 (1.4-8.9) mg/dL vs 3.1 (0.8-9.8) mg/dL (P = .73), respectively. The clinical primary end point rate was 14.0% in the control group (7 of 50 patients) and 1.8% in the colchicine group (1 of 55 patients) (odds ratio, 0.11; 95% CI, 0.01-0.96; P = .02). Mean (SD) event-free survival time was 18.6 (0.83) days the in the control group vs 20.7 (0.31) in the colchicine group (log rank P = .03). Adverse events were similar in the 2 groups, except for diarrhea, which was more frequent with colchicine group than the control group (25 patients [45.5%] vs 9 patients [18.0%]; P = .003). Conclusions and Relevance: In this randomized clinical trial, participants who received colchicine had statistically significantly improved time to clinical deterioration. There were no significant differences in high-sensitivity cardiac troponin or C-reactive protein levels. These findings should be interpreted with caution. Trial Registration: ClinicalTrials.gov Identifier: NCT04326790.

The Greek study in the effects of colchicine in COvid-19 complications prevention (GRECCO-19 study): Rationale and study design.

OBJECTIVE: Colchicine has been utilized safely in a variety of cardiovascular clinical conditions. Among its potential mechanisms of action is the non-selective inhibition of NLRP3 inflammasome which is thought to be a major pathophysiologic component in the clinical course of patients with COVID-19. GRECCO-19 will be a prospective, randomized, open-labeled, controlled study to assess the effects of colchicine in COVID-19 complications prevention. METHODS: Patients with laboratory confirmed SARS-CoV-2 infection (under RT PCR) and clinical picture that involves temperature >37.5 oC and at least two out of the: i. sustained coughing, ii. sustained throat pain, iii. Anosmia and/or ageusia, iv. fatigue/tiredness, v. PaO2<95 mmHg will be included. Patients will be randomised (1:1) in colchicine or control group. RESULTS: Trial results will be disseminated through peer-reviewed publications and conference presentations. CONCLUSION: GRECCO-19 trial aims to identify whether colchicine may positively intervene in the clinical course of COVID-19. (ClinicalTrials.gov Identifier: NCT04326790).