Investigation of hs-TnI and sST-2 as Potential Predictors of Long-Term Cardiovascular Risk in Patients with Survived Hospitalization for COVID-19 Pneumonia.

INTRODUCTION: COVID-19 survivors reveal an increased long-term risk for cardiovascular disease. Biomarkers like troponins and sST-2 improve stratification of cardiovascular risk. Nevertheless, their prognostic value for identifying long-term cardiovascular risk after having survived COVID-19 has yet to be evaluated. METHODS: In this single-center study, admission serum biomarkers of sST-2 and hs-TnI in a single cohort of 251 hospitalized COVID-19 survivors were evaluated. Concentrations were correlated with major cardiovascular events (MACE) defined as cardiovascular death and/or need for cardiovascular hospitalization during follow-up after hospital discharge [FU: 415 days (403; 422)]. RESULTS: MACE was a frequent finding during FU with an incidence of 8.4% (cardiovascular death: 2.8% and/or need for cardiovascular hospitalization: 7.2%). Both biomarkers were reliable indicators of MACE (hs-TnI: sensitivity = 66.7%&specificity = 65.7%; sST-2: sensitivity = 33.3%&specificity = 97.4%). This was confirmed in a multivariate proportional-hazards analysis: besides age (HR = 1.047, 95% CI = 1.012-1.084, p = 0.009), hs-TnI (HR = 4.940, 95% CI = 1.904-12.816, p = 0.001) and sST-2 (HR = 10.901, 95% CI =4.509-29.271, p < 0.001) were strong predictors of MACE. The predictive value of the model was further improved by combining both biomarkers with the factor age (concordance index hs-TnI + sST2 + age = 0.812). CONCLUSION: During long-term FU, hospitalized COVID-19 survivors, hs-TnI and sST-2 at admission, were strong predictors of MACE, indicating both proteins to be involved in post-acute sequelae of COVID-19.

Early antithrombotic post-discharge therapy using prophylactic DOAC or dipyridamole improves long-term survival and cardiovascular outcomes in hospitalized COVID-19 survivors.

Introduction: Cardiovascular events are common in COVID-19. While the use of anticoagulation during hospitalization has been established in current guidelines, recommendations regarding antithrombotic therapy in the post-discharge period are conflicting. Methods: To investigate this issue, we conducted a retrospective follow-up (393 ± 87 days) of 1,746 consecutive patients, hospitalized with and surviving COVID-19 pneumonia at a single tertiary medical center between April and December 2020. Survivors received either 30-day post-discharge antithrombotic treatment regime using prophylactic direct oral anticoagulation (DOAC; n = 1,002) or dipyridamole (n = 304), or, no post-discharge antithrombotic treatment (Ctrl; n = 440). All-cause mortality, as well as cardiovascular mortality (CVM) and further cardiovascular outcomes (CVO) resulting in hospitalization due to pulmonary embolism (PE), myocardial infarction (MI) and stroke were investigated during the follow-up period. Results: While no major bleeding events occured during follow-up in the treatment groups, Ctrl showed a high but evenly distributed rate all-cause mortality. All-cause mortality (CVM) was attenuated by prophylactic DOAC (0.6%, P < 0.001) and dipyridamole (0.7%, P < 0.001). This effect was also evident for both therapies after propensity score analyses using weighted binary logistic regression [DOAC: B = -3.33 (0.60), P < 0.001 and dipyridamole: B = -3.04 (0.76), P < 0.001]. While both treatment groups displayed a reduced rate of CVM [DOAC: B = -2.69 (0.74), P < 0.001 and dipyridamole: B = -17.95 (0.37), P < 0.001], the effect in the DOAC group was driven by reduction of both PE [B-3.12 (1.42), P = 0.012] and stroke [B = -3.08 (1.23), P = 0.028]. Dipyridamole significantly reduced rates of PE alone [B = -17.05 (1.01), P < 0.001]. Conclusion: Late cardiovascular events and all-cause mortality were high in the year following hospitalization for COVID-19. Application of prophylactic DOAC or dipyridamole in the early post-discharge period improved mid- and long-term CVO and all-cause mortality in COVID-19 survivors.

Cardiovascular Biomarkers for Prediction of in-hospital and 1-Year Post-discharge Mortality in Patients With COVID-19 Pneumonia.

Aims: While COVID-19 affects the cardiovascular system, the potential clinical impact of cardiovascular biomarkers on predicting outcomes in COVID-19 patients is still unknown. Therefore, to investigate this issue we analyzed the prognostic potential of cardiac biomarkers on in-hospital and long-term post-discharge mortality of patients with COVID-19 pneumonia. Methods: Serum soluble ST2, VCAM-1, and hs-TnI were evaluated upon admission in 280 consecutive patients hospitalized with COVID-19-associated pneumonia in a single, tertiary care center. Patient clinical and laboratory characteristics and the concentration of biomarkers were correlated with in-hospital [Hospital stay: 11 days (10; 14)] and post-discharge all-cause mortality at 1 year follow-up [FU: 354 days (342; 361)]. Results: 11 patients died while hospitalized for COVID-19 (3.9%), and 11 patients died during the 1-year post-discharge follow-up period (n = 11, 4.1%). Using multivariate analysis, VCAM-1 was shown to predict mortality during the hospital period (HR 1.081, CI 95% 1.035;1.129, p = 0.017), but not ST2 or hs-TnI. In contrast, during one-year FU post hospital discharge, ST2 (HR 1.006, 95% CI 1.002;1.009, p < 0.001) and hs-TnI (HR 1.362, 95% CI 1.050;1.766, p = 0.024) predicted mortality, although not VCAM-1. Conclusion: In patients hospitalized with Covid-19 pneumonia, elevated levels of VCAM-1 at admission were associated with in-hospital mortality, while ST2 and hs-TnI might predict post-discharge mortality in long term follow-up.

Gender-Specific Differences in the Intensive Care Treatment of COVID-19 Patients.

BACKGROUND: Gender-specific differences in the outcome of COVID-19 patients requiring intensive care treatment have been reported. However, a potential association with ICU therapy remains elusive. METHODS: A total of 224 consecutive patients (63 women) treated for severe COVID-19 disease requiring mechanical ventilation were screened for the study. After propensity score matching for gender, 40 men and 40 women were included in the study. Comparative analysis was conducted for laboratory parameters, ICU therapy and complications (pulmonary embolism, thrombosis, stroke, and ventricular arrhythmias), and outcome (mortality). RESULTS: Male patients had significantly higher levels of CRP (p = 0.012), interleukin-6 (p = 0.020) and creatinine (p = 0.027), while pH levels (p = 0.014) were significantly lower compared to females. Male patients had longer intubation times (p = 0.017), longer ICU stays (p = 0.022) and higher rates of catecholamine dependence (p = 0.037). Outcome, complications and ICU therapy did not differ significantly between both groups. CONCLUSION: The present study represents the first matched comparison of male and female COVID-19 patients requiring intensive care treatment. After propensity matching, male patients still displayed a higher disease severity. This was reflected in higher rates of vasopressors, duration of ICU stay and duration of intubation. In contrast, no significant differences were observed in mortality rates, organ replacement therapy and complications during ICU stay.

Dexamethasone Improves Cardiovascular Outcomes in Critically Ill COVID-19, a Real World Scenario Multicenter Analysis.

BACKGROUND: Severe COVID-19 pneumonia requiring intensive care treatment remains a clinical challenge to date. Dexamethasone was reported as a promising treatment option, leading to a reduction of mortality rates in severe COVID-19 disease. However, the effect of dexamethasone treatment on cardiac injury and pulmonary embolism remains largely elusive. METHODS: In total 178 critically ill COVID-19 patients requiring intensive care treatment and mechanical ventilation were recruited in three European medical centres and included in the present retrospective study. One hundred thirteen patients (63.5%) were treated with dexamethasone for a median duration of 10 days (IQR 9-10). Sixty five patients (36.5%) constituted the non-dexamethasone control group. RESULTS: While peak inflammatory markers were reduced by dexamethasone treatment, the therapy also led to a significant reduction in peak troponin levels (231 vs. 700% indicated as relative to cut off value, p = 0.001). Similar, dexamethasone resulted in significantly decreased peak D-Dimer levels (2.16 mg/l vs. 6.14 mg/l, p = 0.002) reflected by a significant reduction in pulmonary embolism rate (4.4 vs. 20.0%, p = 0.001). The antithrombotic effect of dexamethasone treatment was also evident in the presence of therapeutic anticoagulation (pulmonary embolism rate: 6 vs. 34.4%, p < 0.001). Of note, no significant changes in baseline characteristics were observed between the dexamethasone and non-dexamethasone group. CONCLUSION: In severe COVID-19, anti-inflammatory effects of dexamethasone treatment seem to be associated with a significant reduction in myocardial injury. Similar, a significant decrease in pulmonary embolism, independent of anticoagulation, was evident, emphasizing the beneficial effect of dexamethasone treatment in severe COVID-19.

Higher Incidence of Stroke in Severe COVID-19 Is Not Associated With a Higher Burden of Arrhythmias: Comparison With Other Types of Severe Pneumonia

Aims: Thromboembolic events, including stroke, are typical complications of COVID-19. Whether arrhythmias, frequently described in severe COVID-19, are disease-specific and thus promote strokes is unclear. We investigated the occurrence of arrhythmias and stroke during rhythm monitoring in critically ill patients with COVID-19, compared with severe pneumonia of other origins. Methods and Results: This retrospective study included 120 critically ill patients requiring mechanical ventilation in three European tertiary hospitals, including n =60 COVID-19, matched according to risk factors for the occurrence of arrhythmias in n = 60 patients from a retrospective consecutive cohort of severe pneumonia of other origins. Arrhythmias, mainly atrial fibrillation (AF), were frequent in COVID-19. However, when compared with non-COVID-19, no difference was observed with respect to ventricular tachycardias (VT) and relevant bradyarrhythmias (VT 10.0 vs. 8.4 %, p = ns and asystole 5.0 vs. 3.3%, p = ns) with consequent similar rates of cardiopulmonary resuscitation (6.7 vs. 10.0%, p = ns). AF was even more common in non-COVID-19 (AF 18.3 vs. 43.3%, p = 0.003;newly onset AF 10.0 vs. 30.0%, p = 0.006), which resulted in a higher need for electrical cardioversion (6.7 vs. 20.0%, p = 0.029). Despite these findings and comparable rates of therapeutic anticoagulation (TAC), the incidence of stroke was higher in COVID-19 (6.7.% vs. 0.0, p = 0.042). These events also happened in the absence of AF (50%) and with TAC (50%). Conclusions: Arrhythmias were common in severe COVID-19, consisting mainly of AF, yet less frequent than in matched pneumonia of other origins. A contrasting higher incidence of stroke independent of arrhythmias also observed with TAC, seems to be an arrhythmia-unrelated disease-specific feature of COVID-19.

J-waves in acute COVID-19: A novel disease characteristic and predictor of mortality?

BACKGROUND: J-waves represent a common finding in routine ECGs (5-6%) and are closely linked to ventricular tachycardias. While arrhythmias and non-specific ECG alterations are a frequent finding in COVID-19, an analysis of J-wave incidence in acute COVID-19 is lacking. METHODS: A total of 386 patients consecutively, hospitalized due to acute COVID-19 pneumonia were included in this retrospective analysis. Admission ECGs were analyzed, screened for J-waves and correlated to clinical characteristics and 28-day mortality. RESULTS: J-waves were present in 12.2% of patients. Factors associated with the presence of J-waves were old age, female sex, a history of stroke and/or heart failure, high CRP levels as well as a high BMI. Mortality rates were significantly higher in patients with J-waves in the admission ECG compared to the non-J-wave cohort (J-wave: 14.9% vs. non-J-wave 3.8%, p = 0.001). After adjusting for confounders using a multivariable cox regression model, the incidence of J-waves was an independent predictor of mortality at 28-days (OR 2.76 95% CI: 1.15-6.63; p = 0.023). J-waves disappeared or declined in 36.4% of COVID-19 survivors with available ECGs for 6-8 months follow-up. CONCLUSION: J-waves are frequently and often transiently found in the admission ECG of patients hospitalized with acute COVID-19. Furthermore, they seem to be an independent predictor of 28-day mortality.

Overview of Current International Recommendations for Echocardiography Exams During the Covid-19 Pandemic and Its Local Implementation in Austria.

Since its first appearance in December 2019, the novel Coronavirus SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2) has spread throughout the world at rapid pace causing the coronavirus disease 2019 (Covid-19). Originating in the Chinese province Hubei, more than 91.8 million people globally have now been infected with the coronavirus and more than 1.966.000 patients have died thus far from Covid-19 (as of January 13th 2021). The virus spreads primarily by droplet infection as well as via aerosols during close physical contact. Particularly in medical examinations with close physical contact between examiner and patient, like echocardiography, the risk of contracting the virus is increased. Therefore, the use of personal protective equipment is recommended for the protection of patients and medical personnel alike. In this article, the current recommendations of international professional associations on the use of personal protective equipment and their local implementation are presented.

Myocardial injury in severe COVID-19 is similar to pneumonias of other origin: results from a multicentre study.

AIMS: COVID-19, a respiratory viral disease causing severe pneumonia, also affects the heart and other organs. Whether its cardiac involvement is a specific feature consisting of myocarditis, or simply due to microvascular injury and systemic inflammation, is yet unclear and presently debated. Because myocardial injury is also common in other kinds of pneumonias, we investigated and compared such occurrence in severe pneumonias due to COVID-19 and other causes. METHODS AND RESULTS: We analysed data from 156 critically ill patients requiring mechanical ventilation in four European tertiary hospitals, including all n = 76 COVID-19 patients with severe disease course requiring at least ventilatory support, matched to n = 76 from a retrospective consecutive patient cohort of severe pneumonias of other origin (matched for age, gender, and type of ventilator therapy). When compared to the non-COVID-19, mortality (COVID-19 = 38.2% vs. non-COVID-19 = 51.3%, P = 0.142) and impairment of systolic function were not significantly different. Surprisingly, myocardial injury was even more frequent in non-COVID-19 (96.4% vs. 78.1% P = 0.004). Although inflammatory activity [C-reactive protein (CRP) and interleukin-6] was indifferent, d-dimer and thromboembolic incidence (COVID-19 = 23.7% vs. non-COVID-19 = 5.3%, P = 0.002) driven by pulmonary embolism rates (COVID-19 = 17.1% vs. non-COVID-19 = 2.6%, P = 0.005) were higher. CONCLUSIONS: Myocardial injury was frequent in severe COVID-19 requiring mechanical ventilation, but still less frequent than in similarly severe pneumonias of other origin, indicating that cardiac involvement may not be a specific feature of COVID-19. While mortality was also similar, COVID-19 is characterized with increased thrombogenicity and high pulmonary embolism rates.

[Echocardiographic examinations in times of the COVID-19 pandemic : International recommendations and implementation]. / Echokardiographieuntersuchungen in Zeiten der COVID-19-Pandemie : Internationale Empfehlungen und Umsetzung.

Since its first appearance in December 2019, the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread all over the world at a rapid pace causing the coronavirus disease 2019 (COVID-19). Originating from the Chinese province Hubei, more than 29.4 million people globally have now been confirmed to have contracted the coronavirus and more than 930,000 patients have died so far from COVID-19 (situation as of 15 September 2020). The virus is mainly spread during close contact by small droplets and aerosols. During the close contact in medical examinations, such as echocardiography, the risk of contracting the virus is increased. Therefore, the use of personal protective equipment is recommended for the protection of patients and medical personnel alike. This article summarizes the current recommendations of international societies and describes the local implementation in Austria.

Anti-coagulation for COVID-19 treatment: both anti-thrombotic and anti-inflammatory?

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection has been linked to a higher risk of mortality compared to influenza, which is mainly due to severe secondary diseases, such as acute respiratory distress syndrome (ARDS). In turn, ARDS is characterized by an acute inflammation and an excessive activity of the coagulation cascade, rising the vulnerability for venous thromboembolic events. In order to investigate the relation of inflammation and the influence of coagulation factors on their release, human peripheral mononuclear blood cells (PBMCs) were treated with autologous serum, heparinized plasma and different doses of fibrin. Thereafter, the concentration of pro-inflammatory cytokines and chemokines in the secretome of PBMCs was measured by enzyme-linked immunosorbent assay. Our analyses revealed autologous serum to significantly increase the secretion of cytokines and chemokines after 24 h of incubation time. Furthermore, the addition of fibrin markedly increased the secretion of cytokines and chemokines by PBMCs in a dose-dependent manner. Consequently, in accordance with previous studies, our study outlines that anti-coagulation may constitute a promising tool for the treatment of SARS-CoV-2, reducing both, the cytokine storm, as well as the risk for thrombotic complications.

Effect of the COVID-19 Pandemic on Treatment Delays in Patients with ST-Segment Elevation Myocardial Infarction.

Coronavirus disease 19 (COVID-19) and its associated restrictions could affect ischemic times in patients with ST-segment elevation myocardial infarction (STEMI). The objective of this study was to investigate the influence of the COVID-19 outbreak on ischemic times in consecutive all-comer STEMI patients. We included consecutive STEMI patients (n = 163, median age: 61 years, 27% women) who were referred to seven tertiary care hospitals across Austria for primary percutaneous coronary intervention between 24 February 2020 (calendar week 9) and 5 April 2020 (calendar week 14). The number of patients, total ischemic times and door-to-balloon times in temporal relation to COVID-19-related restrictions and infection rates were analyzed. While rates of STEMI admissions decreased (calendar week 9/10 (n = 69, 42%); calendar week 11/12 (n = 51, 31%); calendar week 13/14 (n = 43, 26%)), total ischemic times increased from 164 (interquartile range (IQR): 107-281) min (calendar week 9/10) to 237 (IQR: 141-560) min (calendar week 11/12) and to 275 (IQR: 170-590) min (calendar week 13/14) (p = 0.006). Door-to-balloon times were constant (p = 0.60). There was a significant difference in post-interventional Thrombolysis in myocardial infarction (TIMI) flow grade 3 in patients treated during calendar week 9/10 (97%), 11/12 (84%) and 13/14 (81%; p = 0.02). Rates of in-hospital death and re-infarction were similar between groups (p = 0.48). Results were comparable when dichotomizing data on 10 March and 16 March 2020, when official restrictions were executed. In this cohort of all-comer STEMI patients, we observed a 1.7-fold increase in ischemic time during the outbreak of COVID-19 in Austria. Patient-related factors likely explain most of this increase. Counteractive steps are needed to prevent further cardiac collateral damage during the ongoing COVID-19 pandemic.