Cardiac Injury in COVID-19: A Systematic Review of Relevant Meta-Analyses

Background: Cardiac injury (CI) is not a rare condition among hospitalized patients with coronavirus disease 2019 (COVID-19). Its prognostic value has been extensively reported through the literature, mainly in the context of observational studies. An impressive number of relevant meta-analyses has been conducted. These meta-analyses present similar and consistent results;yet interesting methodological issues emerge. Methods: A systematic literature search was conducted aiming to identify all relevant meta-analyses on (i) the incidence, and (ii) the prognostic value of CI among hospitalized patients with COVID-19. Results: Among 118 articles initially retrieved, 73 fulfilled the inclusion criteria and were included in the systematic review. Various criteria were used for CI definition mainly based on elevated cardiac biomarkers levels. The most frequently used biomarker was troponin. 30 meta-analyses reported the pooled incidence of CI in hospitalized patients with COVID-19 that varies from 5% to 37%. 32 meta-analyses reported on the association of CI with COVID-19 infection severity, with only 6 of them failing to show a statistically significant association. Finally, 46 meta-analyses investigated the association of CI with mortality and showed that patients with COVID-19 with CI had increased risk for worse prognosis. Four meta-analyses reported pooled adjusted hazard ratios for death in patients with COVID-19 and CI vs those without CI ranging from 1.5 to 3. Conclusions: The impact of CI on the prognosis of hospitalized patients with COVID-19 has gained great interest during the pandemic. Methodological issues such as the inclusion of not peer-reviewed studies, the inclusion of potentially overlapping populations or the inclusion of studies with unadjusted analyses for confounders should be taken into consideration. Despite these limitations, the adverse prognosis of patients with COVID-19 and CI has been consistently demonstrated.

Myocardial injury after major non-cardiac surgery evaluated with advanced cardiac imaging: a pilot study.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) is a frequent complication caused by cardiac and non-cardiac pathophysiological mechanisms, but often it is subclinical. MINS is associated with increased morbidity and mortality, justifying the need to its diagnose and the investigation of their causes for its potential prevention. METHODS: Prospective, observational, pilot study, aiming to detect MINS, its relationship with silent coronary artery disease and its effect on future adverse outcomes in patients undergoing major non-cardiac surgery and without postoperative signs or symptoms of myocardial ischemia. MINS was defined by a high-sensitive cardiac troponin T (hs-cTnT) concentration > 14 ng/L at 48-72 h after surgery and exceeding by 50% the preoperative value; controls were the operated patients without MINS. Within 1-month after discharge, cardiac computed tomography angiography (CCTA) and magnetic resonance imaging (MRI) studies were performed in MINS and control subjects. Significant coronary artery disease (CAD) was defined by a CAD-RADS category ≥ 3. The primary outcomes were prevalence of CAD among MINS and controls and incidence of major cardiovascular events (MACE) at 1-year after surgery. Secondary outcomes were the incidence of individual MACE components and mortality. RESULTS: We included 52 MINS and 12 controls. The small number of included patients could be attributed to the study design complexity and the dates of later follow-ups (amid COVID-19 waves). Significant CAD by CCTA was equally found in 20 MINS and controls (30% vs 33%, respectively). Ischemic patterns (n = 5) and ischemic segments (n = 2) depicted by cardiac MRI were only observed in patients with MINS. One-year MACE were also only observed in MINS patients (15.4%). CONCLUSION: This study with advanced imaging methods found a similar CAD frequency in MINS and control patients, but that cardiac ischemic findings by MRI and worse prognosis were only observed in MINS patients. Our results, obtained in a pilot study, suggest the need of further, extended studies that screened systematically MINS and evaluated its relationship with cardiac ischemia and poor outcomes. Trial registration Clinicaltrials.gov identifier: NCT03438448 (19/02/2018).

Advanced Imaging Supports the Mechanistic Role of Autoimmunity and Plaque Rupture in COVID-19 Heart Involvement.

The cardiovascular system is frequently affected by coronavirus disease-19 (COVID-19), particularly in hospitalized cases, and these manifestations are associated with a worse prognosis. Most commonly, heart involvement is represented by myocarditis, myocardial infarction, and pulmonary embolism, while arrhythmias, heart valve damage, and pericarditis are less frequent. While the clinical suspicion is necessary for a prompt disease recognition, imaging allows the early detection of cardiovascular complications in patients with COVID-19. The combination of cardiothoracic approaches has been proposed for advanced imaging techniques, i.e., CT scan and MRI, for a simultaneous evaluation of cardiovascular structures, pulmonary arteries, and lung parenchyma. Several mechanisms have been proposed to explain the cardiovascular injury, and among these, it is established that the host immune system is responsible for the aberrant response characterizing severe COVID-19 and inducing organ-specific injury. We illustrate novel evidence to support the hypothesis that molecular mimicry may be the immunological mechanism for myocarditis in COVID-19. The present article provides a comprehensive review of the available evidence of the immune mechanisms of the COVID-19 cardiovascular injury and the imaging tools to be used in the diagnostic workup. As some of these techniques cannot be implemented for general screening of all cases, we critically discuss the need to maximize the sustainability and the specificity of the proposed tests while illustrating the findings of some paradigmatic cases.

Short and Long-Term Cardiovascular Sequelae after SARS-CoV-2 Infection: A Narrative Review Focusing on Athletes.

Cardiovascular (CV) involvement after severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection was found to be frequent among the general population, especially in the pre-vaccination era, and particularly for hospitalized patients or those who experienced a more severe course of the disease. The spectrum of CV disease varies; however, acute myocarditis is particularly fearsome for the athletic population due to the possible associated risk of malignant arrhythmias during training. Alarming percentages of CV injuries, even in young and healthy athletes with a benign course of the disease, arose from a few initial studies limited to case series. Subsequent single-center studies and larger observational registries reported a lower prevalence of SARS-CoV2 CV involvement in athletes. Studies showing the occurrence of CV adverse events during follow-up periods are now available. The objective of our narrative review is to provide an updated summary of the literature on CV involvement after coronavirus disease 2019, both in the early post-infection period and over a longer period of time, with a focus on athletic populations.

COVID-19-associated myocardial injury: A case report.

Coronavirus disease 2019 (COVID-19) is often accompanied by pneumonia and can be fatal. We report a case of COVID-19-associated myocardial injury mimicking fulminant myocarditis. Endomyocardial biopsy revealed numerous von Willebrand factor-rich microthrombi with small myocardial necrotic areas, complement deposits in small vessels/microthrombi, and macrophage-predominant interstitial infiltration. These findings, distinct from those of typical lymphocytic myocarditis, show diffuse endothelial injury, complement activation, and activated macrophages as characteristic features of COVID-19-associated pathogenesis. Dysregulated serum cytokine profiles predicting severe/critical COVID-19-associated myocardial injury were also determined. This case emphasizes the occurrence of fatal cardiac manifestation with microthrombotic injury in the early stage of COVID-19.

Bibliometric evaluation of 2020-2022 publications on COVID-19-related cardiovascular disease.

Objective: This study aimed to investigate the international scientific output regarding the relationship between COVID-19 and cardiovascular diseases (CVDs) through a bibliometric analysis and explore research hotspots in this field. Methods: We searched the Web of Science Core Collection for publications and used different types of software, such as R, CiteSpace, and VOSviewer, to analyze and visualize the data. Results: A total of 10,055 publications were retrieved as of the 13 December 2022, based on the inclusion criteria after screening. The USA and China lead in the quantity and quality of publications in this field. Based on Bradford's law, 63 journals were considered core journals in the field. Co-cited references and keywords analysis indicated that researchers paid particular attention to cardiovascular comorbidities, outcomes, and COVID-19 regenerative medicine. In summary, with increasing COVID-19 research related to CVD, more attention might be drawn to the relationship between these two diseases. Conclusion: The hotspots in this field may continue to revolve around cardiovascular comorbidities, outcomes, and COVID-19 regenerative medicine. Owing to the different situations faced by different groups with COVID-19, further exploration of the related factors specific to each of these groups, e.g., history or no history of heart failure, is needed, with a view to providing a reference for intervention measures in COVID-19 research.

Frequency and prognosis of CVD and myocardial injury in patients presenting with suspected COVID-19 - The CoV-COR registry.

Background: The COVID-19 pandemic led to an alteration of algorithms in emergency medicine, which may influence the management of patients with similar symptoms but underlying cardiovascular diseases. We evaluated key differential diagnoses to acute COVID-19 infection and the prevalence and the prognosis of myocardial injury in patients presenting for suspected COIVD-19 infection. Methods: This prospective observational study includes patients presenting with symptoms suggestive of COVID-19 infection during the pandemic. In patients without COVID-19, leading diagnoses was classified according to ICD-10. Myocardial injury was defined as elevated high-sensitivity Troponin I with at least one value above the 99th percentile upper reference limit and its prevalence together with 90-days mortality rate was compared in patients with vs without COVID-infection. Results: From 497 included patients (age 62.9 ± 17.2 years, 56 % male), 314 (63 %) were tested positive on COVID-19 based on PCR-testing, while another cause of symptom was detected in 183 patients (37 %). Cardiovascular diseases were the most frequent differential diagnoses (40 % of patients without COVID-19), followed by bacterial infection (24 %) and malignancies (16 %). Myocardial injury was present in 91 patients (COVID-19 positive: n = 34, COVID-19 negative: n = 57). 90-day mortality rate was higher in patients with myocardial injury (13.4 vs 4.6 %, p = 0.009). Conclusion: Cardiovascular diseases represent the most frequent differential diagnoses in patients presenting to a tertiary care emergency department with symptoms suggestive of an acute infection. Screening for cardiovascular disease is crucial in the initial evaluation of symptomatic patients during the COVID pandemic to identify patients at increased risk.Trial Registration:Clinicaltrials.gov Identifier: NCT04327479.

Site-level variability in the processes of care and outcomes over time among patients with COVID-19 and myocardial injury: Insights from the American Heart Association's COVID-19 Cardiovascular Disease Registry.

Background: Elevated cardiac troponin (cTn) levels in patients with COVID-19 has been associated with worse outcomes. Guidelines on best practices of those patients remain uncertain. Methods: We included patients with COVID-19 and cTn above the assay-specific upper limit of normal (ULN) enrolled in the American Heart Association's COVID-19 registry between March 2020-January 2021. Site-level variability in invasive coronary angiography, LVEF assessment, ICU utilization, and inpatient mortality were determined by calculating adjusted median odds ratio (MOR) using hierarchical logistic regression models. Temporal trends were assessed with Cochran-Armitage trend test. Results: Among 32,636 patients, we included 6234 (19.4 %) with cTn above ULN (age 68.7 ± 16.0 years, 56.5 % male, 51.5 % Caucasian), of whom 1365 (21.6 %) had ≥5-fold elevations. Across 55 sites, the median rate of invasive coronary angiography was 0.1 % with adjusted MOR 1.5(1.0,2.3), median LVEF assessment was 25.5 %, MOR 3.0(2.2,3.9), ICU utilization was 41.7 %, MOR 2.2(1.8,2.6), and mortality was 20.9 %, MOR 1.7(1.5,2.0). Over time, we noted a significant increase in invasive coronary angiography (p-trend = 0.001), and LVEF assessment (p-trend<0.001), and reduction in mortality (p-trend<0.001), without significant change in ICU admissions (p-trend = 0.08). Similar variability and temporal trends were seen among patients with ≥5-fold cTn elevation. Conclusions: The use of invasive coronary angiography among patients with COVID-19 and myocardial injury was very low during the early pandemic. We found moderate institutional variability in processes of care with an uptrend in invasive catheterization and LVEF assessment, and downtrend in mortality. Comparative effectiveness studies are needed to examine whether variability in care is associated with differences in outcomes.

Cardiac Arrhythmias in Post-COVID Syndrome: Prevalence, Pathology, Diagnosis, and Treatment.

An increase in post-COVID patients with late sequelae of acute COVID-19 infection is emerging as an ongoing challenge for physicians and healthcare professionals. Since the beginning of the pandemic, it has rapidly become evident that the acute infection is not limited to the respiratory tract but that several organs, including the cardiovascular system, can be affected. Moreover, in a significant proportion of patients (ranging from about 10 to up to 50%) with former COVID-19, cardiopulmonary symptoms such as dyspnea, palpitations, restricted physical capacity, and cardiac arrhythmias can persist weeks and months after the acute SARS-CoV-2 infection. The spectrum of COVID-19-associated arrhythmias is rather wide, most likely due to various pathomechanisms. In this article, the prevalence of cardiac arrhythmias and underlying pathologies are reviewed, including direct myocardial injury and abnormal consequences with an impact on cardiac electric instability. The hyperinflammatory reaction of the host immune system is specifically considered. Moreover, several distinct rhythm disorders occurring in post-COVID patients are discussed with regard to their clinical management.

Evaluation of electrocardiographic changes in patients under COVID-19 treatment regimes

Background and Aim: Awareness of electrocardiographic (ECG) changes is crucial in patients who receive coronavirus disease 2019 (COVID-19) treatment. In this study, we aimed to evaluate ECG parameters in patients under COVID-19 therapy and their relationship with the severity of lung involvement and the disease on the basis of thoracic computerized tomography (TCT) findings and laboratory parameters. Material(s) and Method(s): Of 350 patients hospitalized due to COVID-19 between March 2020 and June 2020, 300 patients with available data were retrospectively analyzed. Blood analysis, electrocardiographic, and clinical findings were evaluated. Six-month follow-up data were also recorded. Result(s): The patients were categorized into two groups: Survivor (n = 206, 68.7%, Group 1) and nonsurvivor patients (n = 94, 31.3%, Group 2). The mean total follow-up period was 125.39 +/- 73.09 days. The mean age was similar in both groups. In multivariate regression analysis that aimed to predict COVID-19 disease severity, it was found that besides increased C-reactive protein and D-dimer levels, and >=50% lung involvement in TCT, which are well known as bad prognostic factors, the corrected QT interval duration (QTc) prolongation >=60 miliseconds (msn) during hospitalization was associated with worse prognosis in COVID-19 patients during follow-up. Conclusion(s): Our study is the first study that demonstrated that the presence of >=60 msn QTc prolongation during hospital stay was found to be the most valuable ECG parameter to predict the prognosis and had a significant association with >=50% lung involvement in TCT in patients under anti-COVID therapy. Close monitoring of this ECG parameter is important both in terms of treatment planning and interpretation of disease progression. Copyright © 2022 Society of Cardiovascular Academy. All rights reserved.

Myocardial Injury on CMR in Patients With COVID-19 and Suspected Cardiac Involvement.

BACKGROUND: Myocardial injury in patients with COVID-19 and suspected cardiac involvement is not well understood. OBJECTIVES: The purpose of this study was to characterize myocardial injury in a multicenter cohort of patients with COVID-19 and suspected cardiac involvement referred for cardiac magnetic resonance (CMR). METHODS: This retrospective study consisted of 1,047 patients from 18 international sites with polymerase chain reaction-confirmed COVID-19 infection who underwent CMR. Myocardial injury was characterized as acute myocarditis, nonacute/nonischemic, acute ischemic, and nonacute/ischemic patterns on CMR. RESULTS: In this cohort, 20.9% of patients had nonischemic injury patterns (acute myocarditis: 7.9%; nonacute/nonischemic: 13.0%), and 6.7% of patients had ischemic injury patterns (acute ischemic: 1.9%; nonacute/ischemic: 4.8%). In a univariate analysis, variables associated with acute myocarditis patterns included chest discomfort (OR: 2.00; 95% CI: 1.17-3.40, P = 0.01), abnormal electrocardiogram (ECG) (OR: 1.90; 95% CI: 1.12-3.23; P = 0.02), natriuretic peptide elevation (OR: 2.99; 95% CI: 1.60-5.58; P = 0.0006), and troponin elevation (OR: 4.21; 95% CI: 2.41-7.36; P < 0.0001). Variables associated with acute ischemic patterns included chest discomfort (OR: 3.14; 95% CI: 1.04-9.49; P = 0.04), abnormal ECG (OR: 4.06; 95% CI: 1.10-14.92; P = 0.04), known coronary disease (OR: 33.30; 95% CI: 4.04-274.53; P = 0.001), hospitalization (OR: 4.98; 95% CI: 1.55-16.05; P = 0.007), natriuretic peptide elevation (OR: 4.19; 95% CI: 1.30-13.51; P = 0.02), and troponin elevation (OR: 25.27; 95% CI: 5.55-115.03; P < 0.0001). In a multivariate analysis, troponin elevation was strongly associated with acute myocarditis patterns (OR: 4.98; 95% CI: 1.76-14.05; P = 0.003). CONCLUSIONS: In this multicenter study of patients with COVID-19 with clinical suspicion for cardiac involvement referred for CMR, nonischemic and ischemic patterns were frequent when cardiac symptoms, ECG abnormalities, and cardiac biomarker elevations were present.

Clinical profile and the extent of residual myocardial dysfunction among patients with previous coronavirus disease 2019.

BACKGROUND: Many patients who have recovered from their coronavirus disease 2019 (COVID-19) episode continue to remain symptomatic and seek medical opinion. The clinical characteristics and echocardiography findings of such subjects have not been adequately studied. METHODS: The study included 472 subjects (age 54.0 ± 13.4 years, 57% men) with previous COVID-19 (median duration since COVID-19 12.0 weeks, interquartile range 9.0-26.0 weeks) and 100 controls (age 53.9 ± 13.6 years, 53% men). All subjects underwent detailed clinical assessment and echocardiography, including measurement of left ventricular (LV) ejection fraction (EF) and global longitudinal strain (GLS). RESULTS: Less than third (29.2%) of the post-COVID subjects had needed hospitalization for their initial infection. Exertional dyspnea or breathing difficulty at rest were the commonest reasons for post-COVID presentation. As compared to controls, the post-COVID subjects had impaired LV systolic (LVEF 63.2 ± 2.2 vs. 61.9 ± 4.6, P = 0.007; GLS - 19.9 ± 2.6% vs. -17.6 ± 3.4%, P < 0.001) and diastolic function. Majority of those with reduced LV GLS had preserved LVEF. The patients presenting before 12 weeks were more likely to be symptomatic, but LV GLS did not differ. The patients needing hospitalization had higher burden of co-morbidities and significantly reduced LV GLS as compared to those who had received domiciliary treatment. The patients in the lowest GLS tertile were older, had higher burden of co-morbidities, and had had more severe initial infection with greater need for hospitalization, oxygen therapy and steroids. The need for hospitalization was independently associated with lower GLS at the time of current presentation. CONCLUSION: This study shows that impairment of LV systolic and diastolic function is common among subjects recovering from previous COVID-19 episode. The patients with more severe initial infection have more marked impairment of LV function and this impairment persists even after several months of recovery from the initial infection. Routine measurement of GLS may be helpful since LV systolic dysfunction in these patients is mostly subclinical.

Non-Ischemic, Non-Hypoxic Myocardial Injury, and Long-Term Mortality in Patients with Coronavirus Disease 2019: A Retrospective Cohort Study.

Objective: Cardiac damage is commonly reported in patients with coronavirus disease 2019 (COVID-19) but its prevalence and impact on the long-term survival of patients remain uncertain. This study aimed to explore the prevalence of myocardial injury and assess its prognostic value in patients with COVID-19. Methods: A single-center, retrospective cohort study was performed at the Affiliated Hospital of Jianghan University. Data from 766 patients with confirmed COVID-19 who were hospitalized from December 27, 2019 to April 25, 2020 were collected. Demographic, clinical, laboratory, electrocardiogram, treatment data and all-cause mortality during follow-up were collected and analyzed. Results: Of the 766 patients with moderate to critically ill COVID-19, 86 (11.2%) died after a mean follow-up of 72.8 days. Myocardial injury occurred in 94 (12.3%) patients. The mortality rate was 64.9% (61/94) and 3.7% (25/672) in patients with and without myocardial injury, respectively. Cox regression showed that myocardial injury was an independent risk factor for mortality (hazard ratio: 8.76, 95% confidence interval: 4.76-16.11, P < 0.001). Of the 90 patients with myocardial injury with electrocardiogram results, sinus tachycardia was present in 29, bundle branch block in 26, low voltage in 10, and abnormal T-wave in 53. Conclusions: COVID-19 not only involves pneumonia but also cardiac damage. Myocardial injury is a common complication and an independent risk factor for mortality in COVID-19 patients.

The Evolving Impact of Myocardial Injury in Patients With COVID-19 Amid the Omicron Wave of the Pandemic.

COVID-19 with myocardial injury, defined as troponin elevation, is associated with worse outcomes. The temporal changes in outcomes during various phases of the pandemic remain unclear. We evaluated outcomes during the Omicron phase compared with previous phases of the pandemic. We analyzed patients who were COVID-19-positive with evidence of myocardial injury who presented to the MedStar Health system (11 hospitals in Washington, District of Columbia, and Maryland) during phase 1 of the pandemic (March to June 2020), phase 2 (October 2020 to January 2021), and phase 3 (Omicron; December 2021 to March 2022), comparing their characteristics and outcomes. The primary end point was in-hospital mortality. The cohort included 2,079 patients admitted who were COVID-19 positive and for whom troponin was elevated (phase 1: n = 150, phase 2: n = 854, phase 3: n = 1,075). Baseline characteristics were similar overall. Inflammatory markers were significantly elevated in phase 1 compared with phases 2 and 3. The use of remdesivir and dexamethasone was highest in phase 2. In phase 3, 52.6% of patients were fully vaccinated. In-hospital mortality, though high, was lower in phase 3 than in phases 1 and 2 (59.3% vs 28.1% vs 23.3%; p <0.001). Patients who were vaccinated showed more favorable in-hospital outcomes than did those who were unvaccinated (18.3% vs 24.2%, p = 0.042). In conclusion, patients with COVID-19 with elevated troponin during phase 3 tended to have improved outcomes when compared with patients in earlier waves of the pandemic. This improvement could be attributed to the implementation of the COVID-19 vaccines, advances in COVID-19 treatment options, provider experience, and less virulent variants.

Cardiac Presentation of Multisystem Infammatory Syndrome in Children (MIS-C)

Coronavirus disease 2019 (COVID-19) is usually mild in children. Rarely, children are severely afected. Multisystem infammatory syndrome in children (MIS-C) is an uncommon complication of COVID-19 often involving previously healthy older children and adolescents. It is thought to be the result of an abnormal immune response to the infection. Most afected children have negative polymerase chain reaction (PCR) and positive serology for SARS-CoV-2. Clinical presentation may include persistent fever, gastrointestinal symptoms and features like Kawasaki disease (KD) followed by shock or multisystem involvement. Infammatory markers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], D-dimer and procalcitonin) and cardiac biomarkers (Troponin, brain natriuretic peptide [BNP] or N-terminal proBNP [NT-proBNP]) are often elevated. Evidence of infection (PCR, antigen test or positive serology) or likely contact with COVID-19 patients should accompany. Myocardial injury, identifed by the presence of cardiac troponin above the 99th percentile upper reference limit, is common. Possible causes include viral myocarditis, infammation, hypoxia, stress cardiomyopathy and ischemia. Combinations of these mechanisms could be responsible for cardiac dysfunction. A minority of patients present cardiac symptoms or nonspecifc symptoms. ST-segment and T-wave changes, arrhythmia or heart block may occur on electrocardiography (ECG) although most patients have non-specifc ECG. Depressed left ventricular (LV) function, Coronary artery (CA) dilation or aneurysm, mitral valve regurgitation or pericardial efusion may occur on echocardiographic evaluation. Management depends on the clinical presentation and severity. All patients should receive empiric antibiotic and also antiviral therapy if evidence of active infection exists. Patients presenting shock are treated with intravenous fuid and vasoactive agents. Signifcant LV dysfunction necessitates supportive care to maintain hemodynamics, intravenous immune globulin (IVIG), diuretics and inotropes and rarely mechanical hemodynamic support. For patients with KD features, standard therapies are applied. Glucocorticoid therapy is recommended for severe or refractory shock, KD-like features with risk of IVIG resistance risk and persistent fever. Systemic anticoagulation is used for moderate to severe LV dysfunction and also older children and adolescents with moderate to severe MIS-C. The mortality rate is approximately 1 to 2 percent for MIS-C patients. Most children with cardiac involvement have recovery of ventricular function and resolution of arrhythmias at the time of hospital discharge, although mildly diastolic ventricular dysfunction usually persists in 20%.

Synergistic effect of myocardial injury and mid-regional proAdrenomedullin elevation in determining clinical outcomes of SARS-CoV-2 patients.

Objective: Coronavirus disease 2019 (COVID-19) is a systemic disease induced by SARS-CoV-2 causing myocardial injury. To date, there are few data on the correlation between mid-regional proAdrenomedullin (MR-proADM) and myocardial injury. The aim of this study was to evaluate whether the association of myocardial injury and elevated mid-regional proAdrenomedullin values could predict mortality of SARS-CoV-2 patients, to offer the best management to COVID-19 patients. Materials and methods: All patients hospitalized for SARS-CoV-2 infection at the COVID-19 Center of the Campus Bio-Medico of Rome University were included between October 2020 and March 2021 and were retrospectively analyzed. Myocardial injury was defined as rising and/or fall of cardiac hs Troponin I values with at least one value above the 99th percentile of the upper reference limit (≥15.6 ng/L in women and ≥34.2 ng/L in men). The primary outcome was 30-day mortality. Secondary outcomes were the comparison of MR-proADM, CRP, ferritin, and PCT as diagnostic and prognostic biomarkers of myocardial injury. Additionally, we analyzed the development of ARDS, the need for ICU transfer, and length of stay (LOS). Results: A total of 161 patients were included in this study. Of these, 58 (36.0%) presented myocardial injury at admission. An MR-proADM value ≥ 1.19 nmol/L was defined as the optimal cut-off to identify patients with myocardial injury (sensitivity 81.0% and specificity 73.5%). A total of 121 patients (75.2%) developed ARDS, which was significantly more frequent among patients with myocardial injury (86.2 vs. 68.9%, p = 0.015). The overall 30-day mortality was 21%. Patients with myocardial injury presented significantly higher mortality compared to those without the same (46.6 vs. 6.8%, p < 0.001). When dividing the entire study population into four groups, based on the presence of myocardial injury and MR-proADM values, those patients with both myocardial injury and MR-proADM ≥ 1.19 nmol/L presented the highest mortality (53.2%, p < 0.001). The combination of myocardial injury and MR-proADM values ≥ 1.19 nmol/L was an independent predictor of death (OR = 7.82, 95% CI = 2.87-21.30; p < 0.001). Conclusion: The study is focused on the correlation between myocardial injury and MR-proADM. Myocardial injury induced by SARS-CoV-2 is strongly associated with high MR-proADM values and mortality.

Cardiac adverse reactions of COVID-19 vaccination: cardiac MRI findings.

BACKGROUND: The rapid development of COVID-19 vaccines in the wake of the COVID-19 pandemic has led to an equally expediently deployed vaccination campaign with more than 12 billion vaccinations administered worldwide. Reports of vaccine-associated adverse reactions (VAARs) have ranged from headaches and pain at the injection site to potentially life-threatening events such as cerebral venous sinus thrombosis. The heart has also not been spared of VAARs, as vaccine-associated myocardial infarction and more commonly, albeit still rare, myocarditis and perimyocarditis have been reported in predominantly young male recipients. METHODOLOGICAL INNOVATIONS: Cardiac magnetic resonance imaging findings of vaccine-associated myocarditis such as prolonged T1 and T2 relaxation times, increased T2 signal intensity ratio, and subepicardial late gadolinium enhancement have been demonstrated to be similar to those in virus-induced myocarditis, enabling the use of the modified 2018 Lake Louise Criteria for diagnostic purposes to confirm vaccination-associated myocardial inflammation. Other reported cardiac findings such as cardiomyopathies and arrhythmias were confined to case reports. The incidence of myocardial infarction was not noted to be higher than in the overall population. CONCLUSION: The overall preliminary prognosis of vaccine- associated myocarditis seems to be good as suggested by initial reports, but long-term follow-up is needed to sufficiently assess possible sequelae and consequences.

Cardiovascular Complications in Kidney Transplant Recipients with COVID-19: A Case Series.

Kidney transplant recipients (KTRs) are at a higher risk for developing severe COVID-19 which can be associated with cardiovascular complications. We studied five KTRs recipients infected with COVID-19 who developed severe cardiovascular complications. Two patients presented with ST segment myocardial infarction and two with clinically suspected myocarditis. One patient presented with atrial fibrillation. Two of these patients developed cardiogenic shock. Inflammatory markers were at peak during the event in four of these who had presented with severe COVID-19. Coronary angiography done in two patients with STEMI did not reveal any evidence of atherosclerotic coronary artery disease. Also, based on the cardiovascular (CV) risk estimation by Framingham score, four patients had low CV risk and one patient had intermediate CV risk. All five patients survived. Even with low CV risk, KTRs can develop myocardial injury and arrhythmias solely because of severe COVID-19.

Myocardial Injury and Altered Gene Expression Associated With SARS-CoV-2 Infection or mRNA Vaccination.

SARS CoV-2 enters host cells via its Spike protein moiety binding to the essential cardiac enzyme angiotensin-converting enzyme (ACE) 2, followed by internalization. COVID-19 mRNA vaccines are RNA sequences that are translated into Spike protein, which follows the same ACE2-binding route as the intact virion. In model systems, isolated Spike protein can produce cell damage and altered gene expression, and myocardial injury or myocarditis can occur during COVID-19 or after mRNA vaccination. We investigated 7 COVID-19 and 6 post-mRNA vaccination patients with myocardial injury and found nearly identical alterations in gene expression that would predispose to inflammation, coagulopathy, and myocardial dysfunction.