Myocardial Injury In COVID-19 Research Articles

Vaccines and Myocardial Injury in Patients Hospitalized for COVID-19 Infection: the CardioCOVID-Gemelli Study.

Myocardial injury is prevalent among patients hospitalized for COVID-19. However, the role of COVID-19 vaccines in modifying the risk of myocardial injury is unknown. To assess the role of vaccines in modifying the risk of myocardial injury in COVID-19. We enrolled COVID-19 patients admitted from March 2021 to February 2022 with known vaccination status and ≥1 assessment of hs-cTnI within 30 days from the admission. The primary endpoint was the occurrence of myocardial injury (hs-cTnI levels >99th percentile upper reference limit). 1019 patients were included (mean age 67.7±14.8 years, 60.8% male, 34.5% vaccinated against COVID-19). Myocardial injury occurred in 145 (14.2%) patients. At multivariate logistic regression analysis, advanced age, chronic kidney disease and hypertension, but not vaccination status, were independent predictors of myocardial injury. In the analysis according to age tertiles distribution, myocardial injury occurred more frequently in the III tertile (≥76 years) compared to other tertiles (I tertile:≤60 years;II tertile:61-75 years) (p<0.001). Moreover, in the III tertile, vaccination was protective against myocardial injury (OR 0.57, CI 95% 0.34-0.94; p=0.03), while a previous history of coronary artery disease was an independent positive predictor. In contrast, in the I tertile, chronic kidney disease (OR 6.94, 95% CI 1.31-36.79, p=0.02) and vaccination (OR 4.44, 95% CI 1.28-15.34, p=0.02) were independent positive predictors of myocardial injury. In patients ≥76 years, COVID-19 vaccines were protective for the occurrence of myocardial injury, while in patients ≤60 years, myocardial injury was associated with previous COVID-19 vaccination. Further studies are warranted to clarify the underlying mechanisms.

Myocardial injury in COVID-19: A case series

The COVID-19 pandemic has affected nearly millions of populations worldwide. The range of symptomatology is vast, though predominantly respiratory, and ranges from mild flu-like symptoms to severe respiratory illness with acute respiratory distress syndrome. COVID-19 is associated with many non-respiratory complications affecting the heart, kidneys, gastrointestinal system, central nervous system, and blood vessels. Myocardial injury in COVID-19 patients has varied presentations ranging from arrhythmias, myocardial infarction, myocarditis, and cardiomyopathy to cardiogenic shock. It is usually associated with elevated levels of cardiac biomarkers, with or without any changes in electrocardiography or cardiac imaging. Diagnosis may be difficult based on clinical symptoms or electrocardiogram changes alone, and it can be made using 2D echocardiography, coronary angiogram, CT coronary angiogram, or cardiac magnetic resonance imaging, depending on clinical suspicion. COVID-19-associated cardiac injury increases overall morbidity and mortality. In this case series, five COVID-19 cases with different cardiac manifestations were reported with the intention of presenting the various manifestations of cardiac complications, the course of the disease, and the challenges associated with the complications. This case series showed that cardiac complications are common in the 2nd week during the cytokine storm phase, and timely case-specific specialized diagnostic and therapeutic cardiac interventions might improve the chances of patient survival.

Significance of myocardial injury on in-hospital clinical outcomes of in-hospital and COVID-19 patients.

Acute Myocardial injury defined by increased troponin I level is associated with poor in-hospital outcomes and cardiovascular complications in patients with COVID-19. The current study was designed to determine the implications and clinical outcome of myocardial injury in COVID-19. This retrospective study included hospitalized COVID-19 patients. Myocardial injury was defined by high sensitivity Troponin I (hs-TNI)≥26ng/l. Cardiac biomarkers, inflammatory markers and clinical data were systemically collected and analyzed. Hazard ratio for in-hospital mortality and logistic regression for predictors of acute myocardial injury were analyzed. Of the 1821 total patients with COVID-19, 293(16.09%) patients died and 1528 (83.91%) patients survived. Patients who died had significantly higher association with presence of cardiovascular risk factors, severe CTSS ( CT severity score ) and myocardial injury as compared to survived group. 628 (34.5%) patients had evidence of myocardial injury and they had statistically significant association with cardiovascular risk factors, in-hospital mortality, procalcitonin; higher hospital, and ICCU stay. We found significant hazard ratio of diabetes (HR=2.66, (CI:1.65-4.29)), Severe CT score (HR=2.81, (CI:1.74-4.52)), hs-TNI≥26 ng/l (HR=4.68, (CI:3.81-5.76)) for mortality. Severe CTSS score (OR=1.95, CI: 1.18-3.23, P=0.01) and prior CVD history (OR=1.65, CI:1.00-2.73, P=0.05) were found significant predictors of myocardial injury in regression analysis. Almost one third of hospitalized patients had evidence of acute myocardial injury during hospitalization. Acute myocardial injury is associated with higher hospital and ICCU stay, mortality, higher in-hospital infection which indicates more severe disease and the poor in-hospital outcomes.

Abstract P3121: Serological Mechanisms Driving Cardiotoxicity In Covid-19

Cardiac involvement is common in patients severely ill with COVID-19 and is associated with increased morbidity and mortality. The mechanism for myocardial injury in COVID-19 has been proposed to be at least in part due to a direct viral cytotoxic effect on cardiomyocytes. Preclinical data corroborate the notion that SARSCoV-2 can enter and replicate within hiPSC-derived cardiomyocytes. However, clinical evidence demonstrating direct viral effects on the heart remains limited. Alternatively, cardiac injury may result from excessive inflammatory cytokine production which is the main driver for the pathogenesis in COVID-19. Despite this, cardiotoxicity secondary to hyperinflammation constitutes a potentially amenable mechanism that remains largely unexplored. To investigate serological drivers of cardiotoxicity in COVID-19 we have established a bioassay that assessed the effects of serum from COVID-19 confirmed patients on human embryonic stem cell-derived cardiomyocytes (hESC-CMs). We demonstrate that serum from COVID-19 positive patients significantly reduced cardiomyocyte viability and contractility independent of viral transduction. Serum from patients with greater disease severity led to worse cardiomyocyte viability and this significantly correlated with levels of key inflammatory cytokines, including IL-6, TNF-α, IL1-β, IL-10, CRP and neutrophil to lymphocyte ratio with a specific reduction of CD4+ and CD8+ cells. Combinatorial blockade of IL-6 and TNF-α partially reversed the phenotype and preserved cardiomyocyte viability and function. Interestingly, treatment with serum from Systemic Inflammatory Response Syndrome (SIRS) patients recapitulates the effect observed with COVID-19 patients’ serum indicating that the phenotype observed is most likely not unique to COVID-19 disease. In conclusion, our results provide direct evidence that inflammatory cytokines are at least in part responsible for the cardiovascular damage seen in COVID-19 and indicate possible targets for therapeutic intervention.

Myocardial Injury in COVID-19 and Its Implications in Short- and Long-Term Outcomes.

COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still a pandemic with high mortality and morbidity rates. Clinical manifestation is widely variable, including asymptomatic or mild respiratory tract illness to severe pneumonia and death. Myocardial injury is a significant pathogenic feature of COVID-19 and it is associated with worse in-hospital outcomes, mainly due to a higher number of hospital readmissions, with over 50% mortality. These findings suggest that myocardial injury would identify COVID-19 patients with higher risk during active infection and mid-term follow-up. Potential contributors responsible for myocardial damage are myocarditis, vasculitis, acute inflammation, type 1 and type 2 myocardial infarction. However, there are few data about cardiac sequelae and its long-term consequences. Thus, the optimal screening tool for residual cardiac sequelae, clinical follow-up, and the benefits of a specific cardiovascular therapy during the convalescent phase remains unknown. This mini-review explores the different mechanisms of myocardial injury related to COVID-19 and its short and long-term implications.

Clinical Characterization and Possible Pathological Mechanism of Acute Myocardial Injury in COVID-19.

COVID-19 is a respiratory disease that can cause damage to multiple organs throughout the body. Cardiovascular complications related to COVID-19 mainly include acute myocardial injury, heart failure, acute coronary syndrome, arrhythmia, myocarditis. Among them, myocardial injury is the most common complication in COVID-19 hospitalized patients, and is associated with poor prognosis such as death and arrhythmias. There is a continuous relationship between myocardial injury and the severity of COVID-19. The incidence of myocardial injury is higher in critically ill patients and dead patients, and myocardial injury is more likely to occur in the elderly critically ill patients with comorbidities. Myocardial injury is usually accompanied by more electrocardiogram abnormalities, higher inflammation markers and more obvious echocardiographic abnormalities. According to reports, COVID-19 patients with a history of cardiovascular disease have a higher in-hospital mortality, especially in the elder patients. At present, the mechanism of myocardial injury in COVID-19 is still unclear. There may be direct injury of myocardial cells, systemic inflammatory response, hypoxia, prethrombotic and procoagulant state, myocardial interstitial fibrosis, interferon-mediated immune response and coronary artery plaque instability and other related factors, and angiotensin-converting enzyme-2 receptor may play a key role in the myocardial injury in COVID-19.

Serial Assessment of Myocardial Injury Markers in Mechanically Ventilated Patients With SARS-CoV-2 (from the Prospective MaastrICCht Cohort)

Myocardial injury in COVID-19 is associated with in-hospital mortality. However, the development of myocardial injury over time and whether myocardial injury in patients with COVID-19 at the intensive care unit is associated with outcome is unclear. This study prospectively investigates myocardial injury with serial measurements over the full course of intensive care unit admission in mechanically ventilated patients with COVID-19. As part of the prospective Maastricht Intensive Care COVID cohort, predefined myocardial injury markers, including high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and electrocardiographic characteristics were serially collected in mechanically ventilated patients with COVID-19. Linear mixed-effects regression was used to compare survivors with nonsurvivors, adjusting for gender, age, APACHE-II score, daily creatinine concentration, hypertension, diabetes mellitus, and obesity. In 90 patients, 57 (63%) were survivors and 33 (37%) nonsurvivors, and a total of 628 serial electrocardiograms, 1,565 hs-cTnT, and 1,559 NT-proBNP concentrations were assessed. Log-hs-cTnT was lower in survivors compared with nonsurvivors at day 1 (β −0.93 [−1.37; −0.49], p <0.001) and did not change over time. Log-NT-proBNP did not differ at day 1 between both groups but decreased over time in the survivor group (β −0.08 [−0.11; −0.04] p <0.001) compared with nonsurvivors. Many electrocardiographic abnormalities were present in the whole population, without significant differences between both groups. In conclusion, baseline hs-cTnT and change in NT-proBNP were strongly associated with mortality. Two-thirds of patients with COVID-19 showed electrocardiographic abnormalities. Our serial assessment suggests that myocardial injury is common in mechanically ventilated patients with COVID-19 and is associated with outcome.

COCARDE Study-Cardiac Imaging Phenotype in Patients With COVID-19: Protocol for a Prospective Observational Study.

BackgroundThe effects of SARS-CoV-2 (COVID-19) on the myocardium and their role in the clinical course of infected patients are still unknown. The severity of SARS-CoV-2 is driven by hyperinflammation, and the effects of SARS-CoV-2 on the myocardium may be significant. This study proposes to use bedside observations and biomarkers to characterize the association of COVID-19 with myocardial injury.ObjectiveThe aim of the study is to describe the myocardial function and its evolution over time in patients infected with SARS-CoV-2 and to investigate the link between inflammation and cardiac injury.MethodsThis prospective, monocentric, observational study enrolled 150 patients with suspected or confirmed SARS-CoV-2 infection at Toulouse University Hospital, Toulouse, France. Patients admitted to the intensive care unit (ICU), regular cardiologic ward, and geriatric ward of our tertiary university hospital were included during the pandemic period. Blood sampling, electrocardiography, echocardiography, and morphometric and demographic data were prospectively collected.ResultsA total of 100 patients were included. The final enrolment day was March 31, 2020, with first report of results at the end of the first quarter of 2021. The first echocardiographic results at admission of 31 patients of the COCARDE-ICU substudy population show that biological myocardial injury in COVID-19 has low functional impact on left ventricular systolic function.ConclusionsA better understanding of the effects of COVID-19 on myocardial function and its link with inflammation would improve patient follow-up and care.Trial RegistrationClinicaltrials.gov NCT04358952; https://clinicaltrials.gov/ct2/show/NCT04358952International Registered Report Identifier (IRRID)DERR1-10.2196/24931

Multi-modality imaging of inflammation and ischemia for assessment of myocardial injury in Covid-19

Multi-modality imaging of inflammation and ischemia for assessment of myocardial injury in Covid-19

The Pathogenesis of COVID-19 Myocardial Injury: An Immunohistochemical Study of Postmortem Biopsies.

RationaleMyocardial injury associates significantly and independently with mortality in COVID-19 patients. However, the pathogenesis of myocardial injury in COVID-19 remains unclear, and cardiac involvement by SARS-CoV-2 presents a major challenge worldwide.ObjectiveThis histological and immunohistochemical study sought to clarify the pathogenesis and propose a mechanism with pathways involved in COVID-19 myocardial injury.Methods and ResultsPostmortem minimally invasive autopsies were performed in six patients who died from COVID-19, and the myocardium samples were compared to a control group (n=11). Histological analysis was performed using hematoxylin-eosin and toluidine blue staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against targets: caspase-1, caspase-9, gasdermin-d, ICAM-1, IL-1β, IL-4, IL-6, CD163, TNF-α, TGF-β, MMP-9, type 1 and type 3 collagen. The samples were also assessed for apoptotic cells by TUNEL. Histological analysis showed severe pericardiocyte interstitial edema and higher mast cells counts per high-power field in all COVID-19 myocardium samples. The IHC analysis showed increased expression of caspase-1, ICAM-1, IL-1β, IL-6, MMP-9, TNF-α, and other markers in the hearts of COVID-19 patients. Expression of caspase-9 did not differ from the controls, while gasdermin-d expression was less. The TUNEL assay was positive in all the COVID-19 samples supporting endothelial apoptosis.ConclusionsThe pathogenesis of COVID-19 myocardial injury does not seem to relate to primary myocardiocyte involvement but to local inflammation with associated interstitial edema. We found heightened TGF-β and interstitial collagen expression in COVID-affected hearts, a potential harbinger of chronic myocardial fibrosis. These results suggest a need for continued clinical surveillance of patients for myocardial dysfunction and arrythmias after recovery from the acute phase of COVID-19.

The Prognostic Value of Cardiac Biomarkers and Echocardiography in Critical COVID-19.

Background: Early risk stratification is crucial in critically ill COVID-19 patients. Myocardial injury is associated with worse outcome. This study aimed to evaluate cardiac biomarkers and echocardiographic findings in critically ill COVID-19 patients and to assess their association with 30-day mortality in comparison to other biomarkers, risk factors and clinical severity scores.Methods: Prospective, single-center, cohort study in patients with PCR-confirmed, critical COVID-19. Laboratory assessment included high sensitive troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) on admission to ICU: a hs-cTnT ≥ 14 pg/mL and a NT-proBNP ≥ 450 pg/mL were considered as elevated. Transthoracic echocardiographic evaluation was performed within the first 48 h of ICU admission. The primary outcome was 30-day all-cause mortality. Predictive markers for mortality were assessed by ROC analysis and cut-off values by the Youden Index.Results: A total of 100 patients were included. The median age was 63.5 years, the population was predominantly male (66%). At the time of ICU admission, 47% of patients had elevated hs-cTnT and 39% had elevated NT-proBNP. Left ventricular ejection fraction was below 50% in 19.1%. Elevated cardiac biomarkers (hs-cTnT P-value < 0.001, NT-proBNP P-value = 0.001) and impaired left ventricular function (P-value = 0.011) were significantly associated with mortality, while other biomarkers (D-dimer, ferritin, C-reactive protein) and clinical scores (SOFA) did not differ significantly between survivors and non-survivors. An optimal cut-off value to predict increased risk for 30-day all-cause mortality was 16.5 pg/mL for hs-cTnT (OR 8.5, 95% CI: 2.9, 25.0) and 415.5 pg/ml for NT-proBNP (OR 5.1, 95% CI: 1.8, 14.7).Conclusion: Myocardial injury in COVID-19 is common. Early detection of elevated hs-cTnT and NT-proBNP are predictive for 30-day mortality in patients with critical COVID-19. These markers outperform other routinely used biomarkers, as well as clinical indices of disease severity in ICU. The additive value of routine transthoracic echocardiography is disputable and should only be considered if it is likely to impact therapeutic management.

Mechanisms of myocardial injury and clinical outcomes in patients hospitalised with suspected COVID-19

Abstract Background Myocardial injury is associated with adverse outcomes in patients with COVID-19. However, the prognostic role of myocardial injury in COVID-19 compared to other acute illnesses and the underlying mechanisms of injury are poorly understood. Methods In a prospective, multi-centre, cohort study conducted in secondary and tertiary care hospitals in Scotland, all consecutive patients with suspected COVID-19 underwent cardiac troponin (ARCHITECTSTAT high-sensitive troponin I (hs-cTnI) assay; Abbott Laboratories) testing in plasma that was surplus to clinical requirements. The results were not reported unless required by the attending clinician. We evaluated the prevalence of myocardial injury, mechanisms and outcomes in all patients. In those with any hs-cTnI concentration above the sex-specific 99th centile the diagnosis was adjudicated according to the 4th Universal Definition of Myocardial Infarction. The primary outcome of all-cause mortality was compared in those with and without myocardial injury and COVID-19 by cox regression adjusted for age, sex, renal function and co-morbidities. Results A total of 2,916 (median age 69 [interquartile range, IQR 54–79] years, 53% women) consecutive patients with suspected COVID-19 were followed up for 228 [IQR 203–249] days. Myocardial injury occurred in 26% (750/2,916) with a median troponin concentration of 66 [35–178] ng/L; the prevalence was 41% (46/112) and 25% (704/2,804) in those with and without COVID-19, respectively. The most common mechanism was acute non-ischaemic myocardial injury occurring in 80% (37/46) and 71% (502/704) of patients with and without COVID-19, respectively. Type 1 myocardial infarction (2% and 4%), type 2 myocardial infarction (7% and 14%) and chronic myocardial injury (11% and 11%) were less common and only one patient had confirmed myocarditis. In patients with myocardial injury mortality was increased compared to those without (P&amp;lt;0.001 log rank), whether they had COVID-19 (54% [25/46] versus 26% [17/66]) or not (35% [248/704] versus 14% [294/2100]). Myocardial injury was an independent predictor of death in all patients (adjusted hazard ratio [aHR] 2.04, 95% confidence interval [CI] 1.71 to 2.43), but this excess risk was not higher in patients with COVID-19 (aHR 1.58, 95% CI 0.75 to 3.15) compared to those without the condition (aHR 2.01, 95% CI 1.81 to 2.49). Conclusion Myocardial injury is common in hospitalised patients with suspected COVID-19 whether or not COVID-19 was the cause of their presentation. The majority of patients had acute non-ischaemic myocardial injury rather than a defined cardiac condition. Despite this the presence of myocardial injury was an independent predictor of death in all hospitalised patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): British Heart Foundation Kaplan-Meier curve for all-cause death

Cardiac MRI and Myocardial Injury in COVID-19: Diagnosis, Risk Stratification and Prognosis.

Myocardial injury is a common complication of the COVID-19 illness and is associated with a worsened prognosis. Systemic hyperinflammation seen in the advanced stage of COVID-19 likely contributes to myocardial injury. Cardiac magnetic resonance imaging (CMR) is the preferred imaging modality for non-invasive evaluation in acute myocarditis, enabling risk stratification and prognostication. Modified scanning protocols in the pandemic setting reduce risk of exposure while providing critical data regarding cardiac tissue inflammation and fibrosis, chamber remodeling, and contractile function. The growing use of CMR in clinical practice to assess myocardial injury will improve understanding of the acute and chronic sequelae of myocardial inflammation from various pathological etiologies.

Myocardial injury in COVID-19

Myocardial injury in COVID-19

Myocardial Injury in COVID-19: A Tale of Two Syndromes

Myocardial injury is seen in many patients with severe COVID-19. These researchers compared myocardial injury related to severe COVID-19 in 243

СЕРЦЕВО-СУДИННІ УСКЛАДНЕННЯ У ПАЦІЄНТІВ ІЗ COVID-19

Cardiovascular system is one of the most vulnerable during COVID-19. The main mechanisms of cardiac injury are: direct myocardial damage, mediated by viral binding to angiotensin-converting-ensyme-2, cardiac microvascular damage and thrombosis, caused by hypercoagulability. Cardiovascular complications such as acute and chronic myocardial injury, myocarditis, myocardial infarction, pulmonary embolism, stress-cardiomyopathy, arterial and venous thrombosis and arrhythmic disorders are common among COVID-19 patients. Myocardial injury in COVID-19 could have different mechanisms and may occur at early and late stages of the COVID-19 disease, resulting in myocardial dysfunction and heart failure. Echocardiography is a first-line noninvasive imaging method to assess the cardiac injury during COVID 19 while cardiac magnetic resonance imaging is the best to identify myocardial oedema, inflammation and fibrosis. In this article we presented the analysis of experience of cardiologists in different countries concerning diagnostics ant treatment of COVID-19 related cardiovascular pathology and case reports from our own experience concerning cardiovascular complications of COVID-19. Laboratory diagnostics (troponin and brain-natriuretic peptide) and noninvasive imaging methods (echocardiography and cardiac magnetic resonance tomography) are essential to confirm the diagnosis of cardiac injury in COVID-19 and to evaluate the effect of the treatment. Long-term follow-up studies are needed to understand better the COVID-19 related cardiac pathology.

Abstract 17183: Severity of Myocardial Injury in COVID-19 Hospitalized Patients

Introduction: Myocardial injury in COVID19 is reported as high as 30% and associated with worsened prognosis (Cooper et al., Circulation). Along with elevated cardiac biomarkers, elevated inflammatory markers of cytokine storm and hemophagocytic lymphohistiocytosis (HLH) are associated with increased illness severity and mortality. Our study aimed to identify patients at highest risk for myocardial injury and subsequent cardiac decompensation. Methods: 279 consecutive patients with COVID19 from a major metropolitan academic center, discharged from 3-21-2020 to 5-17-2020, were analyzed. Primary data includes age, sex, race, and peak troponin I during hospitalization. Patients were further stratified to evaluate severe cases with acute respiratory distress syndrome (ARDS) requiring intubation (n=40), and peak levels of CRP, ferritin, and D-dimer were collected. Bivariate and multivariate measures of association between peak inflammatory marker and troponin I levels were estimated. Results: Average age of ARDS population patients was 61 +/- 15 years; 50% male and 50% female. Self-identified African Americans(AA) were 35%, Hispanic/Latinos(H/L) were 55%, and Others including two White Americans were 10%. Average peak troponin I in H/L was remarkably higher 0.51 +/-1.16 compared to AA 0.18 +/- 0.23 and Others 0.13 +/- 0.16. Per multivariate regression analysis, D-dimer had the most significant effect on the elevated troponin (p=0.027). Although weakly significant, H/L showed elevated troponin (p =0.09) compared to non-H/L. Conclusion: Elevated D-dimer is associated with increased morbidity in COVID19, and also correlates with elevated troponin concerning for increased myocardial injury. Furthermore, the H/L population may be at greater risk for developing myocardial injury and have more injury as shown by higher troponin I levels. Larger studies may better assess the relation between inflammatory markers such as CRP and ferritin and myocardial injury. Our study provides evidence of systemic inflammation contributing to significant myocardial injury in COVID19, especially in the H/L population. Identifying patients at highest risk for myocardial injury early may allow for more effective medical interventions and improved outcomes.

A recovered patient after myocardial injury related to Covid-19; a case report

ACE2 receptors are reported to have an important role in myocardial injury in Covid-19. Direct myocardial toxic effect of virus, myocarditis, cytokine injury, microangiopathic injury related to virus infection may cause myocardial injury and eventually troponin levels increase. Those mechanisms are; unstable plaques in coronary arteries resulting in myocardial hypoxia, upregulation of ACE2 receptors in coronary arteries and cardiac tissue, direct toxic effect of virus towards myocytes, systemic inflammation, myocardial interstitial fibrosis, excessive immune response to interferon, increased cytokine release from helper T lymphocytes which lead to myocardial injury. In this reported case, clinical course was mild and outcome was good, patient was followed in ward and he did not need intensive care.