Impact of the COVID-19 pandemic on acute coronary syndromes.

AIM: To assess the impact of the first wave of the COVID-19 pandemic on acute coronary syndromes and on the delay from symptom onset to first medical contact among patients presenting with ST-segment elevation myocardial infarction (STEMI), as well as to investigate whether there were patient-related reasons related to COVID-19 for delaying first medical contact. METHODS AND RESULTS: All patients undergoing percutaneous coronary intervention (PCI) at the Geneva University Hospitals for acute coronary syndromes (ACS) during the first COVID-19 wave were compared with a control group consisting of all ACS patients who underwent PCI during the same period in 2019 and those treated in the period immediately preceding the pandemic. The primary outcome measure was the difference in the delay from symptom onset to first medical contact in the setting of STEMI between the COVID-19 period and the control period. Secondary outcome measures were the difference in ACS incidence and the impact of the COVID-19 pandemic on patients’ decisions to call the emergency services, assessed using a questionnaire. Delay from symptom onset to first medical contact was longer among patients suffering from STEMI in the COVID-19 period compared with the control period (112 min vs 60 min, p = 0.049). The incidence rate of ACS was lower during the COVID-19 period (incidence rate ratio 0.6, 95% confidence interval [CI] 0.449–0.905). ACS patients delayed their call to the emergency services mainly because of fear of contracting or spreading COVID-19 following hospital admission, as well as of adding burden to the healthcare system. CONCLUSION: We observed prolonged delays from symptom onset to first medical contact and a decline in overall ACS incidence during the first wave of the COVID-19 pandemic, with a higher threshold to call for help among ACS patients.

High-Sensitivity Troponin: A Review on Characteristics, Assessment, and Clinical Implications.

The use of high-sensitivity cardiac troponin (hs-cTn) assays has become part of the daily practice in most of the laboratories worldwide in the initial evaluation of the typical chest pain. Due to their early surge, the use of hs-cTn may reduce the time needed to recognise myocardial infarctions (MI), which is vital for the patients presenting in the emergency departments for chest pain. The latest European Society of Cardiology Guidelines did not only recognise their central role in the diagnosis algorithm but also recommended their use for rapid rule-in/rule-out of MI. High-sensitivity cardiac troponins are also powerful prognostic markers for long-term events and mortality, not only in a wide spectrum of other cardiovascular diseases (CVD) but also in several non-CVD pathologies. Moreover, these biomarkers became a powerful tool in special populations, such as paediatric patients and, most recently, COVID-19 patients. Although highly investigated, the assessment and interpretation of the hs-cTn changes are still challenging in the patients with basal elevation such as CKD or critically ill patients. Moreover, there are still various analytical characteristics not completely understood, such as circadian or sex variability, with major clinical implications. In this context, the present review focuses on summarizing the most recent research in the current use of hs-cTn, with a main consideration for its role in the diagnosis of MI but also its prognostic value. We have also carefully selected the most important studies regarding the challenges faced by clinicians from different specialties in the correct interpretation of this biomarker. Moreover, future perspectives have been proposed and analysed, as more research and cross-disciplinary collaboration are necessary to improve their performance.

SARS-CoV-2 vaccination and myocarditis or myopericarditis: population based cohort study.

OBJECTIVE: To investigate the association between SARS-CoV-2 vaccination and myocarditis or myopericarditis. DESIGN: Population based cohort study. SETTING: Denmark. PARTICIPANTS: 4 931 775 individuals aged 12 years or older, followed from 1 October 2020 to 5 October 2021. MAIN OUTCOME MEASURES: The primary outcome, myocarditis or myopericarditis, was defined as a combination of a hospital diagnosis of myocarditis or pericarditis, increased troponin levels, and a hospital stay lasting more than 24 hours. Follow-up time before vaccination was compared with follow-up time 0-28 days from the day of vaccination for both first and second doses, using Cox proportional hazards regression with age as an underlying timescale to estimate hazard ratios adjusted for sex, comorbidities, and other potential confounders. RESULTS: During follow-up, 269 participants developed myocarditis or myopericarditis, of whom 108 (40%) were 12-39 years old and 196 (73%) were male. Of 3 482 295 individuals vaccinated with BNT162b2 (Pfizer-BioNTech), 48 developed myocarditis or myopericarditis within 28 days from the vaccination date compared with unvaccinated individuals (adjusted hazard ratio 1.34 (95% confidence interval 0.90 to 2.00); absolute rate 1.4 per 100 000 vaccinated individuals within 28 days of vaccination (95% confidence interval 1.0 to 1.8)). Adjusted hazard ratios among female participants only and male participants only were 3.73 (1.82 to 7.65) and 0.82 (0.50 to 1.34), respectively, with corresponding absolute rates of 1.3 (0.8 to 1.9) and 1.5 (1.0 to 2.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively. The adjusted hazard ratio among 12-39 year olds was 1.48 (0.74 to 2.98) and the absolute rate was 1.6 (1.0 to 2.6) per 100 000 vaccinated individuals within 28 days of vaccination. Among 498 814 individuals vaccinated with mRNA-1273 (Moderna), 21 developed myocarditis or myopericarditis within 28 days from vaccination date (adjusted hazard ratio 3.92 (2.30 to 6.68); absolute rate 4.2 per 100 000 vaccinated individuals within 28 days of vaccination (2.6 to 6.4)). Adjusted hazard ratios among women only and men only were 6.33 (2.11 to 18.96) and 3.22 (1.75 to 5.93), respectively, with corresponding absolute rates of 2.0 (0.7 to 4.8) and 6.3 (3.6 to 10.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively. The adjusted hazard ratio among 12-39 year olds was 5.24 (2.47 to 11.12) and the absolute rate was 5.7 (3.3 to 9.3) per 100 000 vaccinated individuals within 28 days of vaccination. CONCLUSIONS: Vaccination with mRNA-1273 was associated with a significantly increased risk of myocarditis or myopericarditis in the Danish population, primarily driven by an increased risk among individuals aged 12-39 years, while BNT162b2 vaccination was only associated with a significantly increased risk among women. However, the absolute rate of myocarditis or myopericarditis after SARS-CoV-2 mRNA vaccination was low, even in younger age groups. The benefits of SARS-CoV-2 mRNA vaccination should be taken into account when interpreting these findings. Larger multinational studies are needed to further investigate the risks of myocarditis or myopericarditis after vaccination within smaller subgroups.

Incidence of Myopericarditis and Myocardial Injury in Coronavirus Disease 2019 Vaccinated Subjects.

Several recent publications have described myopericarditis cases after the coronavirus disease 2019 (COVID-19) vaccination. However, it is uncertain if these cases occurred secondary to the vaccination or more common etiologies of myopericarditis. To help determine whether a correlation exists between COVID-19 vaccination and myopericarditis, the present study compared the gender-specific cumulative incidence of myopericarditis and myocardial injury in a cohort of COVID-19 vaccinated patients at a tertiary care center in 2021 with the cumulative incidence of these conditions in the same subjects exactly 2 years earlier. We found that the age-adjusted incidence rate of myopericarditis in men was higher in the vaccinated than the control population, rate ratio 9.7 (p = 0.04). However, the age-adjusted incidence rate of myopericarditis in women was no different between the vaccinated and control populations, rate ratio 1.28 (p = 0.71). We further found that the rate of myocardial injury was higher in both men and women in 2021 than in 2019 both before and after vaccination, suggesting that some of the apparent increase in the diagnosis of myopericarditis after vaccination may be attributable to factors unrelated to the COVID-19 vaccinations. In conclusion, our study reaffirms the apparent increase in the diagnosis of myopericarditis after COVID-19 vaccination in men but not in women, although this finding may be confounded by increased rates of myocardial injury in 2021. The benefits of COVID-19 vaccination to individual and public health clearly outweigh the small potential increased risk of myopericarditis after vaccination.

Myocardial injury in patients with SARS-CoV-2 pneumonia: Pivotal role of inflammation in COVID-19.

AIMS: Infection by SARS-CoV-2 may result in a systemic disease and a proportion of patients ranging 15%-44% experienced cardiac injury (CI) diagnosed by abnormal troponin levels. The aim of the present study was to analyse the clinical characteristics of a large series of hospitalized patients for COVID-19 in order to identify predisposing and/or protective factors of CI and the outcome. METHODS AND RESULTS: This is an observational, retrospective study on patients hospitalized in two Italian centres (San Raffaele Hospital and Cremona Hospital) for COVID-19 and at least one high-sensitivity cardiac troponin (hs-cTnt) measurement during hospitalization. CI was defined if at least one hs-cTnt value was above the 99th percentile. The primary end-point was the occurrence of CI during hospitalization. We included 750 patients (median age 67, IQR 56-77 years; 69% males), of whom 46.9% had history of hypertension, 14.7% of chronic coronary disease and 22.3% of chronic kidney disease (CKD). Abnormal troponin levels (median troponin 74, IQR 34-147 ng/l) were detected in 390 patients (52%) during the hospitalization. At multivariable analysis age, CKD, cancer, C-reactive protein (CRP) levels were independently associated with CI. Independent predictors of very high troponin levels were chronic kidney disease and CRP levels. Patients with CI showed higher rate of all-cause mortality (40.0% vs. 9.1%, p = 0.001) compared to those without CI. CONCLUSION: This large, multicentre Italian study confirmed the high prevalence of CI and its prognostic role in hospitalized patients with COVID-19, highlighting the leading role of systemic inflammation for the occurrence of CI.

COVID-19 and the Incidence of Acute Myocardial Injury.

Cardiovascular manifestations are frequent in COVID-19 infection and are predictive of adverse outcomes. Elevated cardiac biomarkers are common findings in patients with cardiovascular comorbidities and severe COVID-19 infection. Troponin, inflammatory and thrombotic markers may also improve risk prediction in COVID-19. In our comprehensive review, we provide an overview of the incidence, potential mechanisms and outcome of acute cardiac injury in COVID-19. Thereby, we discuss coagulation abnormalities in sepsis and altered immune response as contributing factors favoring myocardial injury. We further highlight the role of endothelial damage in the pathophysiological concepts. Finally, observational studies addressing the incidence of myocardial infarction during COVID-19 pandemic are discussed.

Endothelial Dysfunction as a Component of Severe Acute Respiratory Syndrome Coronavirus 2-Related Multisystem Inflammatory Syndrome in Children With Shock.

TRIAL REGISTRATION: NCT04420468. OBJECTIVES: Severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children is frequently associated with shock; endothelial involvement may be one of the underlying mechanisms. We sought to describe endothelial dysfunction during multisystem inflammatory syndrome in children with shock and then assess the relationship between the degree of endothelial involvement and the severity of shock. DESIGN: Observational study. SETTING: A PICU in a tertiary hospital. PATIENTS: Patients aged under 18 (n = 28) with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children and shock, according to the Centers for Disease Control and Prevention criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Correlations between endothelial marker levels and shock severity were assessed using Spearman coefficient. The median (interquartile range) age was 9 years (7.5-11.2 yr). Sixteen children presented with cardiogenic and distributive shock, 10 presented with cardiogenic shock only, and two presented with distributive shock only. The median left ventricular ejection fraction, troponin level, and lactate level were, respectively, 40% (35-45%), 261 ng/mL (131-390 ng/mL), and 3.2 mmol/L (2-4.2 mmol/L). Twenty-five children received inotropes and/or vasopressors; the median Vasoactive and Inotropic Score was 8 (5-28). Plasma levels of angiopoietin-2 (6,426 pg/mL [2,814-11,836 pg/mL]), sE-selectin (130,405 pg/mL [92,987-192,499 pg/mL]), von Willebrand factor antigen (344% [288-378%]), and the angiopoietin-2/angiopoietin-1 ratio (1.111 [0.472-1.524]) were elevated and significantly correlated with the Vasoactive and Inotropic Score (r = 0.45, p = 0.016; r = 0.53, p = 0.04; r = 0.46, p = 0.013; and r = 0.46, p = 0.012, respectively). CONCLUSIONS: Endothelial dysfunction is associated with severe acute respiratory syndrome coronavirus 2-related multisystem inflammatory syndrome in children with shock and may constitute one of the underlying mechanisms.

High troponin levels in patients hospitalized for coronavirus disease 2019: a maker or a marker of prognosis?

AIMS: Controversial data have been published regarding the prognostic role of cardiac troponins in patients who need hospitalization because of coronavirus disease 2019 (COVID-19). The aim of the study was to assess the role of high-sensitivity troponin plasma levels and of respiratory function at admission on all-cause deaths in unselected patients hospitalized because of COVID-19. METHODS: We pooled individual patient data from observational studies that assessed all-cause mortality of unselected patients hospitalized for COVID-19. The individual data of 722 patients were included. The ratio of partial pressure arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) and high-sensitivity troponins was reported at admission in all patients. This meta-analysis was registered on PROSPERO (CRD42020213209). RESULTS: After a median follow-up of 14 days, 180 deaths were observed. At multivariable regression analysis, age [hazard ratio (HR) 1.083, 95% confidence interval (CI) 1.061-1.105, P < 0.0001], male sex (HR 2.049, 95% CI 1.319-3.184, P = 0.0014), moderate-severe renal dysfunction (estimated glomerular filtration rate  < 30 mL/min/m2) (HR 2.108, 95% CI 1.237-3.594, P = 0.0061) and lower PaO2/FiO2 (HR 0.901, 95% CI 0.829-0.978, P = 0.0133) were the independent predictors of death. A linear increase in the HR was associated with decreasing values of PaO2/FiO2 below the normality threshold. On the contrary, the HR curve for troponin plasma levels was near-flat with large CI for values above the normality thresholds. CONCLUSION: In unselected patients hospitalized for COVID-19, mortality is mainly driven by male gender, older age and respiratory failure. Elevated plasma levels of high-sensitivity troponins are not an independent predictor of worse survival when respiratory function is accounted for.

Decrease of left ventricular ejection fraction in severe illness patients due to COVID-19 may improve as the disease resolves

Background/aim: Increase in publications supporting myocardial involvement in the COVID-19 disease has led to need to gain insight into the the global burden of heart failure after pandemic. We examined the course of myocardial systolic function in patients without elevated troponin levels. Materials and methods: We performed a prospective study. Patients with high troponin levels were excluded from the study in order to definitively exclude complications known to cause permanent left ventricular systolic dysfunction, such as acute coronary syndromes. Two echocardiographic examinations were performed. The first evaluation was performed within the days of hospitalization, if possible, on the day when dyspnea is severe. The second evaluation was performed during the outpatient clinic controls one month after the patient was recovered. Left ventricular ejection fraction (LVEF) was measured using the biplane method of disks (modified Simpson's rule). Results: In the first evaluation, LVEF was found to be significantly lower in the severe illness group than mild/moderate illness group (50 ± 6% and 59 ± 6%; p = 0.03). LVEF decrease (<50%) was found in fifteen patients (43 ± 4%) and detected as global hypokinesia but not segmental. All of these patients were in the severe illness group. In the second evaluation, LVEFs of the fifteen patients with decreased LVEF in the first evaluation were improved and detected in normal limits (first evaluation = 43 ± 4% and second evaluation = 55 ± 2%, p = 0.01). Conclusion: Considering patients without elevated troponin levels during COVID-19 infection, no permanent systolic dysfunction was detected after first month of recovery. We found that transient myocardial dysfunction may develop in the severe illness group with normal troponin levels, LVEF may decrease in the acute phase and improve with the recovery period.

Coronavirus disease 2019 in patients with cardiovascular disease: clinical features and implications on cardiac biomarkers assessment.

INTRODUCTION: Previous cardiovascular disease (CVD) and myocardial involvement are common in coronavirus disease-19 (COVID-19). We investigated relationships between CVD, cardiac biomarkers and outcome in COVID-19. METHODS: We analyzed n = 252 patients from a multicenter study and provided comparison according to the presence or absence of underlying CVD. Cardiac biomarkers high-sensitivity Troponin [upper reference of normality (URN) 35 pg/ml for Troponin I and 14 pg/ml for Troponin T] and natriuretic peptides (Nt-pro-B-type natriuretic peptide, URN 300 pg/ml and B-type natriuretic peptide, URN 100 pg/ml) were both available in n = 136. RESULTS: Mean age was 69 ±â€Š16 years (56% men, 31% with previous CVD). Raised hs-Troponin and natriuretic peptides were detected in 36 and 50% of the cases respectively. Age, chronic obstructive pulmonary disease, hemoglobin, hs-Troponin and natriuretic peptides were independently associated with underlying CVD (P < 0.05 for all). Compared with the normal biomarkers subgroups, patients with isolated hs-Troponin elevation had higher in-hospital mortality (31 vs. 4%, P < 0.05), similar CVD prevalence (15 vs. 11%) and trend towards higher D-dimer (930 vs. 397 ng/ml, P = 0.140). Patients with both biomarkers elevated had higher age, D-dimer, CVD and in-hospital mortality prevalence compared with other subgroups (all P < 0.05 for trend). Outcome analysis revealed previous CVD [model 1: OR 2.72 (95% CI 1.14-6.49), P = 0.024. model 2: OR 2.65 (95% CI 1.05-6.71), P = 0.039], hs-Troponin (log10) [OR 2.61 (95% CI 1.21-5.66), P = 0.015] and natriuretic peptides (log10) [OR 5.84 (95%CI 2.43-14), P < 0.001] to be independently associated with in-hospital mortality. CONCLUSION: In our population, previous CVD was part of a vulnerable phenotype including older age, comorbidities, increased cardiac biomarkers and worse prognosis. Patients with isolated increase in hs-Troponin suffered higher mortality rates despite low prevalence of CVD, possibly explained by higher COVID-19-related systemic involvement.

COVID-19, cardiovascular diseases and cardiac troponins.

There has been strong evidence of myocardial injury in COVID-19 patients with significantly elevated serum cardiac troponin (cTn). While the exact mechanism of injury is unclear, possible suggested pathological mechanisms of injury are discussed. These include increased susceptibility of the myocardium and endothelium to viral invasion, underlying hyperinflammatory state and subsequent cytokine storm, a hypercoagulable and prothrombotic state, and indirect myocardial injury due to hypoxemia. As a result of these pathological mechanisms in COVID-19 patients, cTn may be elevated largely due to myocarditis, microangiopathy or myocardial infarction. The utility of cTn as a biomarker for measuring myocardial injury in these patients and assessing its ability as a prognostic factor for clinical outcome is also discussed.

The prognostic value of cardiac troponin for 60 day mortality and major adverse events in COVID-19 patients.

BACKGROUND: The variability of coronavirus disease 2019 (COVID-19) illness severity has puzzled clinicians and has sparked efforts to better predict who would benefit from rapid intervention. One promising biomarker for in-hospital morbidity and mortality is cardiac troponin (cTn). METHODS: A retrospective study of 1331 adult patients with COVID-19 admitted to the Rush University System in Illinois, USA was performed. Patients without cTn measurement during their admission or a history of end stage renal disease or stage 5 chronic kidney disease were excluded. Using logistic regression adjusted for baseline characteristics, pre-existing comorbidities, and other laboratory markers of inflammation, cTn was assessed as a predictor of 60-day mortality and severe COVID-19 infection, consisting of a composite of 60-day mortality, need for intensive care unit, or requiring non-invasive positive pressure ventilation or intubation. RESULTS: A total of 772 patients met inclusion criteria. Of these, 69 (8.9%) had mild cTn elevation (> 1 to < 2x upper limit of normal (ULN)) and 46 (6.0%) had severe cTn elevation (≥ 2x ULN). Regardless of baseline characteristics, comorbidities, and initial c-reactive protein, lactate dehydrogenase, and ferritin, when compared to the normal cTn group, mild cTn elevation and severe cTn elevation were predictors of severe COVID-19 infection (adjusted OR [aOR] aOR 3.00 [CI: 1.51 - 6.29], P < 0.01; aOR 9.96 [CI: 2.75 - 64.23], P < 0.01, respectively); severe cTn elevation was a predictor of in-hospital mortality (aOR 2.42 [CI: 1.10 - 5.21], P < 0.05) and 60-day mortality (aOR 2.45 [CI: 1.13 - 5.25], P < 0.05). CONCLUSION: In our cohort, both mild and severe initial cTn elevation were predictors of severe COVID-19 infection, while only severe cTn elevation was predictive of 60-day mortality. First cTn value on hospitalization is a valuable longitudinal prognosticator for COVID-19 disease severity and mortality.

Symptomatic Acute Myocarditis in 7 Adolescents After Pfizer-BioNTech COVID-19 Vaccination.

Trials of coronavirus disease 2019 (COVID-19) vaccination included limited numbers of children, so they may not have detected rare but important adverse events in this population. We report 7 cases of acute myocarditis or myopericarditis in healthy male adolescents who presented with chest pain all within 4 days after the second dose of Pfizer-BioNTech COVID-19 vaccination. Five patients had fever around the time of presentation. Acute COVID-19 was ruled out in all 7 cases on the basis of negative severe acute respiratory syndrome coronavirus 2 real-time reverse transcription polymerase chain reaction test results of specimens obtained by using nasopharyngeal swabs. None of the patients met criteria for multisystem inflammatory syndrome in children. Six of the 7 patients had negative severe acute respiratory syndrome coronavirus 2 nucleocapsid antibody assay results, suggesting no previous infection. All patients had an elevated troponin. Cardiac MRI revealed late gadolinium enhancement characteristic of myocarditis. All 7 patients resolved their symptoms rapidly. Three patients were treated with nonsteroidal antiinflammatory drugs only, and 4 received intravenous immunoglobulin and corticosteroids. In this report, we provide a summary of each adolescent's clinical course and evaluation. No causal relationship between vaccine administration and myocarditis has been established. Continued monitoring and reporting to the US Food and Drug Administration Vaccine Adverse Event Reporting System is strongly recommended.

Association of Myocarditis With BNT162b2 Messenger RNA COVID-19 Vaccine in a Case Series of Children.

Importance: The BNT162b2 (Pfizer-BioNTech) messenger RNA COVID-19 vaccine was authorized on May 10, 2021, for emergency use in children aged 12 years and older. Initial reports showed that the vaccine was well tolerated without serious adverse events; however, cases of myocarditis have been reported since approval. Objective: To review results of comprehensive cardiac imaging in children with myocarditis after COVID-19 vaccine. Design, Setting, and Participants: This study was a case series of children younger than 19 years hospitalized with myocarditis within 30 days of BNT162b2 messenger RNA COVID-19 vaccine. The setting was a single-center pediatric referral facility, and admissions occurred between May 1 and July 15, 2021. Main Outcomes and Measures: All patients underwent cardiac evaluation including an electrocardiogram, echocardiogram, and cardiac magnetic resonance imaging. Results: Fifteen patients (14 male patients [93%]; median age, 15 years [range, 12-18 years]) were hospitalized for management of myocarditis after receiving the BNT162b2 (Pfizer) vaccine. Symptoms started 1 to 6 days after receipt of the vaccine and included chest pain in 15 patients (100%), fever in 10 patients (67%), myalgia in 8 patients (53%), and headache in 6 patients (40%). Troponin levels were elevated in all patients at admission (median, 0.25 ng/mL [range, 0.08-3.15 ng/mL]) and peaked 0.1 to 2.3 days after admission. By echocardiographic examination, decreased left ventricular (LV) ejection fraction (EF) was present in 3 patients (20%), and abnormal global longitudinal or circumferential strain was present in 5 patients (33%). No patient had a pericardial effusion. Cardiac magnetic resonance imaging findings were consistent with myocarditis in 13 patients (87%) including late gadolinium enhancement in 12 patients (80%), regional hyperintensity on T2-weighted imaging in 2 patients (13%), elevated extracellular volume fraction in 3 patients (20%), and elevated LV global native T1 in 2 patients (20%). No patient required intensive care unit admission, and median hospital length of stay was 2 days (range 1-5). At follow-up 1 to 13 days after hospital discharge, 11 patients (73%) had resolution of symptoms. One patient (7%) had persistent borderline low LV systolic function on echocardiogram (EF 54%). Troponin levels remained mildly elevated in 3 patients (20%). One patient (7%) had nonsustained ventricular tachycardia on ambulatory monitor. Conclusions and Relevance: In this small case series study, myocarditis was diagnosed in children after COVID-19 vaccination, most commonly in boys after the second dose. In this case series, in short-term follow-up, patients were mildly affected. The long-term risks associated with postvaccination myocarditis remain unknown. Larger studies with longer follow-up are needed to inform recommendations for COVID-19 vaccination in this population.

The prognostic value of serial troponin measurements in patients admitted for COVID-19.

AIMS: Myocardial injury (MI) in coronavirus disease-19 (COVID-19) is quite prevalent at admission and affects prognosis. Little is known about troponin trajectories and their prognostic role. We aimed to describe the early in-hospital evolution of MI and its prognostic impact. METHODS AND RESULTS: We performed an analysis from an Italian multicentre study enrolling COVID-19 patients, hospitalized from 1 March to 9 April 2020. MI was defined as increased troponin level. The first troponin was tested within 24 h from admission, the second one between 24 and 48 h. Elevated troponin was defined as values above the 99th percentile of normal values. Patients were divided in four groups: normal, normal then elevated, elevated then normal, and elevated. The outcome was in-hospital death. The study population included 197 patients; 41% had normal troponin at both evaluations, 44% had elevated troponin at both assessments, 8% had normal then elevated troponin, and 7% had elevated then normal troponin. During hospitalization, 49 (25%) patients died. Patients with incident MI, with persistent MI, and with MI only at admission had a higher risk of death compared with those with normal troponin at both evaluations (P < 0.001). At multivariable analysis, patients with normal troponin at admission and MI injury on Day 2 had the highest mortality risk (hazard ratio 3.78, 95% confidence interval 1.10-13.09, P = 0.035). CONCLUSIONS: In patients admitted for COVID-19, re-test MI on Day 2 provides a prognostic value. A non-negligible proportion of patients with incident MI on Day 2 is identified at high risk of death only by the second measurement.

Myocarditis Following Immunization With mRNA COVID-19 Vaccines in Members of the US Military.

Importance: Myocarditis has been reported with COVID-19 but is not clearly recognized as a possible adverse event following COVID-19 vaccination. Objective: To describe myocarditis presenting after COVID-19 vaccination within the Military Health System. Design, Setting, and Participants: This retrospective case series studied patients within the US Military Health System who experienced myocarditis after COVID-19 vaccination between January and April 2021. Patients who sought care for chest pain following COVID-19 vaccination and were subsequently diagnosed with clinical myocarditis were included. Exposure: Receipt of a messenger RNA (mRNA) COVID-19 vaccine between January 1 and April 30, 2021. Main Outcomes and Measures: Clinical diagnosis of myocarditis after COVID-19 vaccination in the absence of other identified causes. Results: A total of 23 male patients (22 currently serving in the military and 1 retiree; median [range] age, 25 [20-51] years) presented with acute onset of marked chest pain within 4 days after receipt of an mRNA COVID-19 vaccine. All military members were previously healthy with a high level of fitness. Seven received the BNT162b2-mRNA vaccine and 16 received the mRNA-1273 vaccine. A total of 20 patients had symptom onset following the second dose of an appropriately spaced 2-dose series. All patients had significantly elevated cardiac troponin levels. Among 8 patients who underwent cardiac magnetic resonance imaging within the acute phase of illness, all had findings consistent with the clinical diagnosis of myocarditis. Additional testing did not identify other etiologies for myocarditis, including acute COVID-19 and other infections, ischemic injury, or underlying autoimmune conditions. All patients received brief supportive care and were recovered or recovering at the time of this report. The military administered more than 2.8 million doses of mRNA COVID-19 vaccine in this period. While the observed number of myocarditis cases was small, the number was higher than expected among male military members after a second vaccine dose. Conclusions and Relevance: In this case series, myocarditis occurred in previously healthy military patients with similar clinical presentations following receipt of an mRNA COVID-19 vaccine. Further surveillance and evaluation of this adverse event following immunization is warranted. Potential for rare vaccine-related adverse events must be considered in the context of the well-established risk of morbidity, including cardiac injury, following COVID-19 infection.

Demographic, multi-morbidity and genetic impact on myocardial involvement and its recovery from COVID-19: protocol design of COVID-HEART-a UK, multicentre, observational study.

BACKGROUND: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory illness, myocardial injury is increasingly reported and associated with adverse outcomes. However, the pathophysiology, extent of myocardial injury and clinical significance remains unclear. METHODS: COVID-HEART is a UK, multicentre, prospective, observational, longitudinal cohort study of patients with confirmed COVID-19 and elevated troponin (sex-specific > 99th centile). Baseline assessment will be whilst recovering in-hospital or recently discharged, and include cardiovascular magnetic resonance (CMR) imaging, quality of life (QoL) assessments, electrocardiogram (ECG), serum biomarkers and genetics. Assessment at 6-months includes repeat CMR, QoL assessments and 6-min walk test (6MWT). The CMR protocol includes cine imaging, T1/T2 mapping, aortic distensibility, late gadolinium enhancement (LGE), and adenosine stress myocardial perfusion imaging in selected patients. The main objectives of the study are to: (1) characterise the extent and nature of myocardial involvement in COVID-19 patients with an elevated troponin, (2) assess how cardiac involvement and clinical outcome associate with recognised risk factors for mortality (age, sex, ethnicity and comorbidities) and genetic factors, (3) evaluate if differences in myocardial recovery at 6 months are dependent on demographics, genetics and comorbidities, (4) understand the impact of recovery status at 6 months on patient-reported QoL and functional capacity. DISCUSSION: COVID-HEART will provide detailed characterisation of cardiac involvement, and its repair and recovery in relation to comorbidity, genetics, patient-reported QoL measures and functional capacity. CLINICAL TRIAL REGISTRATION: ISRCTN 58667920. Registered 04 August 2020.

The Impact of COVID-19 Patients With Troponin Elevation on Renal Impairment and Clinical Outcome.

BACKGROUND: Cardiac involvement in coronavirus disease 2019 (COVID-19) is known, manifested by troponin elevation, and these patients have a worse prognosis than patients without myocardial injury. METHODS: We analyzed COVID-19-positive patients who presented to the MedStar Health system (11 hospitals in Washington, DC, and Maryland) during the pandemic (March 1-September 30, 2020). We compared renal function and subsequent in-hospital clinical outcomes based on the presence or absence of troponin elevation. The primary outcome was the incidence of acute kidney injury in COVID-19 patients with troponin elevation. We also evaluated in-hospital mortality, overall and based on the presence and absence of both troponin elevation and renal dysfunction. RESULTS: The cohort included 3386 COVID-19-positive admitted patients for whom troponin was drawn. Of these patients, 195 had troponin elevation (defined as ≥1.0 ng/mL), mean age was 61 ± 16 years, and 51% were men. In-hospital mortality was significantly higher (53.8%) in COVID-19-positive patients with concomitant troponin elevation than in those without troponin elevation (14.5%; p < 0.001). COVID-19-positive patients with troponin elevation had a higher prevalence of renal dysfunction (58.5%) than those without troponin elevation (23.4%; p < 0.001). Further analysis demonstrated that having both troponin elevation and renal dysfunction carried the worst in-hospital prognosis (in-hospital mortality 57.9%; intensive-care-unit admission 76.8%; ventilation requirement 63.2%), as compared to the absence or presence of either. CONCLUSION: COVID-19 patients with troponin elevation are at higher risk for worsening renal function, and these patients subsequently have worse in-hospital clinical outcomes. Efforts should focus on early recognition, evaluation, and intensifying care of these patients.