Vaccination-Associated Myocarditis and Myocardial Injury.

SARS-CoV-2 vaccine-associated myocarditis/myocardial injury should be evaluated in the contexts of COVID-19 infection, other types of viral myocarditis, and other vaccine-associated cardiac disorders. COVID-19 vaccine-associated myocardial injury can be caused by an inflammatory immune cell infiltrate, but other etiologies such as microvascular thrombosis are also possible. The clinical diagnosis is typically based on symptoms and cardiac magnetic resonance imaging. Endomyocardial biopsy is confirmatory for myocarditis, but may not show an inflammatory infiltrate because of rapid resolution or a non-inflammatory etiology. Myocarditis associated with SARS-COVID-19 vaccines occurs primarily with mRNA platform vaccines, which are also the most effective. In persons aged >16 or >12 years the myocarditis estimated crude incidences after the first 2 doses of BNT162b2 and mRNA-1273 are approximately 1.9 and 3.5 per 100 000 individuals, respectively. These rates equate to excess incidences above control populations of approximately 1.2 (BNT162b2) and 1.9 (mRNA-1273) per 100 000 persons, which are lower than the myocarditis rate for smallpox but higher than that for influenza vaccines. In the studies that have included mRNA vaccine and SARS-COVID-19 myocarditis measured by the same methodology, the incidence rate was increased by 3.5-fold over control in COVID-19 compared with 1.5-fold for BNT162b2 and 6.2-fold for mRNA-1273. However, mortality and major morbidity are less and recovery is faster with mRNA vaccine-associated myocarditis compared to COVID-19 infection. The reasons for this include vaccine-associated myocarditis having a higher incidence in young adults and adolescents, typically no involvement of other organs in vaccine-associated myocarditis, and based on comparisons to non-COVID viral myocarditis an inherently more benign clinical course.

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.

Cardiac magnetic resonance -detected myocardial injury is not associated with long-term symptoms in patients hospitalized due to COVID-19.

BACKGROUND: Long-term symptoms are frequent after coronavirus disease 2019 (COVID-19). We studied the prevalence of post-acute myocardial scar on cardiac magnetic resonance imaging (CMR) in patients hospitalized due to COVID-19 and its association with long-term symptoms. MATERIALS AND METHODS: In this prospective observational single-center study, 95 formerly hospitalized COVID-19 patients underwent CMR imaging at the median of 9 months after acute COVID-19. In addition, 43 control subjects were imaged. Myocardial scar characteristic of myocardial infarction or myocarditis were noted from late gadolinium enhancement images (LGE). Patient symptoms were screened using a questionnaire. Data are presented as mean ± standard deviation or median (interquartile range). RESULTS: The presence of any LGE was higher in COVID-19 patients (66% vs. 37%, p<0.01) as was the presence of LGE suggestive of previous myocarditis (29% vs. 9%, p = 0.01). The prevalence of ischemic scar was comparable (8% vs. 2%, p = 0.13). Only two COVID-19 patients (7%) had myocarditis scar combined with left ventricular dysfunction (EF <50%). Myocardial edema was not detected in any participant. The need for intensive care unit (ICU) treatment during initial hospitalization was comparable in patients with and without myocarditis scar (47% vs. 67%, p = 0.44). Dyspnea, chest pain, and arrhythmias were prevalent in COVID-19 patients at follow-up (64%, 31%, and 41%, respectively) but not associated with myocarditis scar on CMR. CONCLUSIONS: Myocardial scar suggestive of possible previous myocarditis was detected in almost one-third of hospital-treated COVID-19 patients. It was not associated with the need for ICU treatment, greater symptomatic burden, or ventricular dysfunction at 9 months follow-up. Thus, post-acute myocarditis scar on COVID-19 patients seems to be a subclinical imaging finding and does not commonly require further clinical evaluation.

Myocardial injury and cardiovascular complications in COVID-19: a cohort study in severe and critical patients. / Lesão miocárdica e complicações cardiovasculares na COVID-19: estudo de coorte em pacientes graves e críticos.

OBJECTIVE: To characterize myocardial injury and cardiovascular complications and their predictors in severe and critical COVID-19 patients admitted to the intensive care unit. METHODS: This was an observational cohort study of severe and critical COVID-19 patients admitted to the intensive care unit. Myocardial injury was defined as blood levels of cardiac troponin above the 99th percentile upper reference limit. Cardiovascular events considered were the composite of deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, acute limb ischemia, mesenteric ischemia, heart failure and arrhythmia. Univariate and multivariate logistic regression or Cox proportional hazard models were used to determine predictors of myocardial injury. RESULTS: Of 567 patients with severe and critical COVID-19 admitted to the intensive care unit, 273 (48.1%) had myocardial injury. Of the 374 patients with critical COVID-19, 86.1% had myocardial injury, and also showed more organ dysfunction and higher 28-day mortality (56.6% versus 27.1%, p < 0.001). Advanced age, arterial hypertension and immune modulator use were predictors of myocardial injury. Cardiovascular complications occurred in 19.9% of patients with severe and critical COVID-19 admitted to the intensive care unit, with most events occurring in patients with myocardial injury (28.2% versus 12.2%, p < 0.001). The occurrence of an early cardiovascular event during intensive care unit stay was associated with higher 28-day mortality compared with late or no events (57.1% versus 34% versus 41.8%, p = 0.01). CONCLUSION: Myocardial injury and cardiovascular complications were commonly found in patients with severe and critical forms of COVID-19 admitted to the intensive care unit, and both were associated with increased mortality in these patients.

OBJETIVO: Caracterizar a lesão miocárdica e as complicações cardiovasculares e seus preditores em pacientes graves e críticos com COVID-19 admitidos à unidade de terapia intensiva. MÉTODOS: Este foi um estudo de coorte observacional em pacientes graves e críticos com COVID-19 admitidos à unidade de terapia intensiva. A lesão miocárdica foi definida como níveis sanguíneos de troponina cardíaca acima do limite de referência superior ao percentil 99. Os eventos cardiovasculares considerados foram combinação de trombose venosa profunda, embolia pulmonar, acidente vascular cerebral, infarto do miocárdio, isquemia aguda de membros, isquemia mesentérica, insuficiência cardíaca e arritmia cardíaca. Regressão logística univariada e multivariada ou modelos de risco proporcional de Cox foram utilizados para determinar os preditores de lesão miocárdica. RESULTADOS: Foram admitidos à unidade de terapia intensiva 567 pacientes graves e críticos com COVID-19, dos quais 273 (48,1%) apresentavam lesão miocárdica. Dos 374 pacientes críticos com COVID-19, 86,1% tinham lesão miocárdica, além de apresentarem mais disfunção orgânica e maior mortalidade aos 28 dias (56,6% versus 27,1%; p < 0,001). Foram preditores de lesão miocárdica idade avançada, hipertensão arterial e uso de imunomoduladores. Complicações cardiovasculares ocorreram em 19,9% dos pacientes graves e críticos com COVID-19 admitidos à unidade de terapia intensiva, e a maioria dos eventos deu-se em pacientes com lesão miocárdica (28,2% versus 12,2%; p < 0,001). A ocorrência de evento cardiovascular precoce durante internação em unidade de terapia intensiva estava associada à maior mortalidade aos 28 dias em comparação com eventos tardios ou inexistentes (57,1% versus 34,0% versus 41,8%; p = 0,01). CONCLUSÃO: Pacientes com formas graves e críticas de COVID-19 admitidos à unidade de terapia intensiva foram comumente diagnosticados com lesão miocárdica e complicações cardiovasculares, e ambas estavam associadas à maior mortalidade nesses pacientes.

Myocardial Injury and Prognosis in Hospitalized COVID-19 Patients in Brazil: Results From The Brazilian COVID-19 Registry. / Lesão Miocárdica e Prognóstico em Pacientes Hospitalizados com COVID-19 no Brasil: Resultados do Registro Nacional de COVID-19.

BACKGROUND: Cardiovascular complications of COVID-19 are important aspects of the disease's pathogenesis and prognosis. Evidence on the prognostic role of troponin and myocardial injury in Latin American hospitalized COVID-19 patients is still scarce. OBJECTIVES: To evaluate myocardial injury as independent predictor of in-hospital mortality and invasive mechanical ventilation support in hospitalized patients, from the Brazilian COVID-19 Registry. METHODS: This cohort study is a substudy of the Brazilian COVID-19 Registry, conducted in 31 Brazilian hospitals of 17 cities, March-September 2020. Primary outcomes included in-hospital mortality and invasive mechanical ventilation support. Models for the primary outcomes were estimated by Poisson regression with robust variance, with statistical significance of p<0.05. RESULTS: Of 2,925 patients (median age of 60 years [48-71], 57.1% men), 27.3% presented myocardial injury. The proportion of patients with comorbidities was higher among patients with cardiac injury (median 2 [1-2] vs. 1 [0-2]). Patients with myocardial injury had higher median levels of brain natriuretic peptide, lactate dehydrogenase, creatine phosphokinase, N-terminal pro-brain natriuretic peptide, and C-reactive protein than patients without myocardial injury. As independent predictors, C-reactive protein and platelet counts were related to the risk of death, and neutrophils and platelet counts were related to the risk of invasive mechanical ventilation support. Patients with high troponin levels presented a higher risk of death (RR 2.03, 95% CI 1.60-2.58) and invasive mechanical ventilation support (RR 1.87, 95% CI 1.57-2.23), when compared to those with normal troponin levels. CONCLUSION: Cardiac injury was an independent predictor of in-hospital mortality and the need for invasive mechanical ventilation support in hospitalized COVID-19 patients.

FUNDAMENTO: As complicações cardiovasculares da COVID-19 são aspectos importantes da patogênese e do prognóstico da doença. Evidências do papel prognóstico da troponina e da lesão miocárdica em pacientes hospitalizados com COVID-19 na América Latina são ainda escassos. OBJETIVOS: Avaliar a lesão miocárdica como preditor independente de mortalidade hospitalar e suporte ventilatório mecânico em pacientes hospitalizados, do registro brasileiro de COVID-19. MÉTODOS: Este estudo coorte é um subestudo do registro brasileiro de COVID-19, conduzido em 31 hospitais brasileiros de 17 cidades, de março a setembro de 2020. Os desfechos primários incluíram mortalidade hospitalar e suporte ventilatório mecânico invasivo. Os modelos para os desfechos primários foram estimados por regressão de Poisson com variância robusta, com significância estatística de p<0,05. RESULTADOS: Dos 2925 pacientes [idade mediana de 60 anos (48-71), 57,1%], 27,3% apresentaram lesão miocárdica. A proporção de pacientes com comorbidades foi maior nos pacientes com lesão miocárdica [mediana 2 (1-2) vs. 1 (0-20)]. Os pacientes com lesão miocárdica apresentaram maiores valores medianos de peptídeo natriurético cerebral, lactato desidrogenase, creatina fosfoquinase, N-terminal do pró-peptídeo natriurético tipo B e proteína C reativa em comparação a pacientes sem lesão miocárdica. Como fatores independentes, proteína C reativa e contagem de plaquetas foram relacionados com o risco de morte, e neutrófilos e contagem de plaquetas foram relacionados ao risco de suporte ventilatório mecânico invasivo. Os pacientes com níveis elevados de troponina apresentaram um maior risco de morte (RR 2,03, IC95% 1,60-2,58) e suporte ventilatório mecânico (RR 1,87;IC95% 1,57-2,23), em comparação àqueles com níveis de troponina normais. CONCLUSÃO: Lesão cardíaca foi um preditor independente de mortalidade hospitalar e necessidade de suporte ventilatório mecânico em pacientes hospitalizados com COVID-19.

Electrocardiogram QRS Complex Duration as a Predictor of Hospital Prognosis in Patients With COVID-19.

Aim      To determine the effect of major electrocardiographic (ECG) parameters on the prognosis of patients with COVID-19.Material and methods  One of systemic manifestations of COVID-19 is heart injury. ECG is the most simple and available method for diagnosing the heart injury, which influences the therapeutic approach. This study included 174 hospitalized patients with COVID-19. Major ECG parameters recorded on admission and their changes before the discharge from the hospital or death of the patient, were analyzed, and the effect of each parameter on the in-hospital prognosis was determined. Results were compared with the left ventricular ejection fraction (LV EF), laboratory data, and results of multispiral computed tomography (MSCT) of the lungs.Results ECG data differed on admission and their changes differed for deceased and discharged patients. Of special interest was the effect of the QRS complex duration at baseline and at the end of treatment on the in-hospital survival and mortality rate. The Cox regression analysis showed that the QRS complex duration (relative risk (RR) 2.07, 95% confidence interval (CI): 1.17-3.66; р=0.01), MSCT data (RR, 1.54; 95 % CI: 1.14-2.092; р=0.005), and glomerular filtration rate (GFR) (RR, 0.98; 95 % CI: 0.96-0.99; р=0.001) had the highest predictive significance. In further comparison of these three indexes, the QRS duration and GFR retained their predictive significance, and a ROC analysis showed that the cut-off QRS complex duration was 125 ms (р=0.001). Patients who developed left bundle branch block (LBBB) in the course of disease also had an unfavorable prognosis compared to other intraventricular conduction disorders (р=0.038). The presence of LBBB was associated with reduced LV EF (р=0.0078). The presence of atrial fibrillation (AF) significantly predetermines a worse outcome both at the start (р=0.011) and at the end of observation (р=0.034). A higher mortality was observed for the group of deceased patients with ST segment deviations, ST elevation (р=0.0059) and ST depression (р=0.028).Conclusion      Thus, the QTc interval elongation, LBBB that developed during the treatment, AF, and increased QRS complex duration are the indicators that determine the in-hospital prognosis of patients with COVID-19. The strongest electrocardiographic predictor for an unfavorable prognosis was the QRS complex duration that allowed stratification of patients to groups of risk.

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).

Myocardial Involvement After Hospitalization for COVID-19 Complicated by Troponin Elevation: A Prospective, Multicenter, Observational Study.

BACKGROUND: Acute myocardial injury in hospitalized patients with coronavirus disease 2019 (COVID-19) has a poor prognosis. Its associations and pathogenesis are unclear. Our aim was to assess the presence, nature, and extent of myocardial damage in hospitalized patients with troponin elevation. METHODS: Across 25 hospitals in the United Kingdom, 342 patients with COVID-19 and an elevated troponin level (COVID+/troponin+) were enrolled between June 2020 and March 2021 and had a magnetic resonance imaging scan within 28 days of discharge. Two prospective control groups were recruited, comprising 64 patients with COVID-19 and normal troponin levels (COVID+/troponin-) and 113 patients without COVID-19 or elevated troponin level matched by age and cardiovascular comorbidities (COVID-/comorbidity+). Regression modeling was performed to identify predictors of major adverse cardiovascular events at 12 months. RESULTS: Of the 519 included patients, 356 (69%) were men, with a median (interquartile range) age of 61.0 years (53.8, 68.8). The frequency of any heart abnormality, defined as left or right ventricular impairment, scar, or pericardial disease, was 2-fold greater in cases (61% [207/342]) compared with controls (36% [COVID+/troponin-] versus 31% [COVID-/comorbidity+]; P<0.001 for both). More cases than controls had ventricular impairment (17.2% versus 3.1% and 7.1%) or scar (42% versus 7% and 23%; P<0.001 for both). The myocardial injury pattern was different, with cases more likely than controls to have infarction (13% versus 2% and 7%; P<0.01) or microinfarction (9% versus 0% and 1%; P<0.001), but there was no difference in nonischemic scar (13% versus 5% and 14%; P=0.10). Using the Lake Louise magnetic resonance imaging criteria, the prevalence of probable recent myocarditis was 6.7% (23/342) in cases compared with 1.7% (2/113) in controls without COVID-19 (P=0.045). During follow-up, 4 patients died and 34 experienced a subsequent major adverse cardiovascular event (10.2%), which was similar to controls (6.1%; P=0.70). Myocardial scar, but not previous COVID-19 infection or troponin, was an independent predictor of major adverse cardiovascular events (odds ratio, 2.25 [95% CI, 1.12-4.57]; P=0.02). CONCLUSIONS: Compared with contemporary controls, patients with COVID-19 and elevated cardiac troponin level have more ventricular impairment and myocardial scar in early convalescence. However, the proportion with myocarditis was low and scar pathogenesis was diverse, including a newly described pattern of microinfarction. REGISTRATION: URL: https://www.isrctn.com; Unique identifier: 58667920.

Different Types of Myocardial Injury due to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Variant.

Coronavirus disease 2019 (COVID-19) associated myocardial injury was caused by various mechanisms. We herein describe 2 cases presenting different types of myocardial injury due to Omicron variant. In both patients, diffuse reduced left ventricular (LV) wall motion in transthoracic echocardiography, electrocardiographic abnormality, and elevated myocardial enzymes were demonstrated. In addition, cardiovascular magnetic resonance (CMR) findings fulfilled the 2018 Lake Louise Criteria (LLC) for myocarditis. However, histological findings in 1 patient showed inflammatory cell infiltration with myocyte degeneration, while those in the other showed interstitial edema without inflammatory cell infiltration. Histological findings were crucial for a differential diagnosis of myocardial injury due to Omicron variant.

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.

Inflammatory biomarkers and cardiac injury in COVID-19 patients.

Introduction: Cardiac injury has received considerable attention due to the higher risk of morbidity and mortality associated with coronavirus disease. However, in a developing country, there is a scarcity of data on cardiac injury in COVID-19 patients related to inflammatory biomarkers. Methods: Therefore, the present research retrospectively analyzes data from three territorial hospitals in Pakistan's Punjab province to investigate the potential impact of the cardiac injury on the mortality and severity of COVID-19-infected patients. We evaluated 2,051 patients between January 16 and April 18, 2022, with confirmed COVID-19. The in-hospital mortality recorded for the selected sample size was about 16.28%. Results: The majority of the participants were identified as male (64%) with a median age of 65 years. Also, fever, fatigue, and dyspnea were reported as common symptoms. An aggregate of 623 patients (30.38%) had a cardiac injury, and when these patients are compared to those without cardiac injury, the participants were significantly older and had more comorbidities with higher leukocyte counts, elevated levels of C-reactive protein, interleukin-6, procalcitonin, myohemoglobin, creatinine kinase-myocardial band, serum creatinine, high-sensitivity troponin-I, N-terminal pro-B-type natriuretic peptide had a significant amount of multiple ground-glass opacity and bilateral pulmonary infiltration in radiographic results. Participants with heart injury required more non-invasive or invasive mechanical respiration than those who did not have a cardiac injury. Individuals with cardiac injury had higher rates of sepsis, acute respiratory distress syndrome (ARDS), d-dimer concentration, and respiratory failure than those without cardiac injury. Patients who had had a cardiac injury died at a higher rate than those who had not suffered cardiac damage. In the multivariable logistic regression analysis, participants with cardiac injury showed greater odds of COVID-19 mortality and were found associated with older age (OR = 1.99, 95% CI = 0.04-3.19), elevated cardiac troponin I (OR = 18.64, 95% CI = 13.16-23.01), the complication of sepsis (OR = 10.39, 95% CI = 7.41-13.39) and ARDS (OR = 6.65, 95% CI = 4.04-8.91). Conclusion: Cardiac injury is a frequent complication among patients with coronavirus-induced infection in Punjab, Pakistan, and it is significantly linked to a greater risk of in-hospital mortality.

Protection of zero-valent iron nanoparticles against sepsis and septic heart failure.

BACKGROUND: Septic heart failure accounts for high mortality rates globally. With a strong reducing capacity, zero-valent iron nanoparticles (nanoFe) have been applied in many fields. However, the precise roles and mechanisms of nanoFe in septic cardiomyopathy remain unknown. RESULTS: NanoFe was prepared via the liquid-phase reduction method and functionalized with the biocompatible polymer sodium carboxymethylcellulose (CMC). We then successfully constructed a mouse model of septic myocardial injury by challenging with cecal ligation and puncture (CLP). Our findings demonstrated that nanoFe has a significant protective effect on CLP-induced septic myocardial injury. This may be achieved by attenuating inflammation and oxidative stress, improving mitochondrial function, regulating endoplasmic reticulum stress, and activating the AMPK pathway. The RNA-seq results supported the role of nanoFe treatment in regulating a transcriptional profile consistent with its role in response to sepsis. CONCLUSIONS: The results provide a theoretical basis for the application strategy and combination of nanoFe in sepsis and septic myocardial injury.

Natural History of Myocardial Injury After COVID-19 Vaccine-Associated Myocarditis.

BACKGROUND: Acute myocarditis is a rare complication of mRNA-based COVID-19 vaccination. Little is known about the natural history of this complication. METHODS: Baseline and convalescent (≥ 90 days) cardiac magnetic resonance (CMR) imaging assessments were performed in 20 consecutive patients meeting Updated Lake Louise Criteria for acute myocarditis within 10 days of mRNA-based vaccination. CMR-based changes in left ventricular volumes, mass, ejection fraction (LVEF), markers of tissue inflammation (native T1 and T2 mapping), and fibrosis (late gadolinium enhancement [LGE] and extracellular volume [ECV]) were assessed between baseline and convalescence. Cardiac symptoms and clinical outcomes were captured. RESULTS: Median age was 23.1 years (range 18-39 years), and 17 (85%) were male. Convalescent evaluations were performed at a median (IQR) 3.7 (3.3-6.2) months. The LVEF showed a mean 3% absolute improvement, accompanied by a 7% reduction in LV end-diastolic volume and 5% reduction in LV mass (all P < 0.015). Global LGE burden was reduced by 66% (P < 0.001). Absolute reductions in global T2, native T1, and ECV of 2.1 ms, 58 ms, and 2.9%, repectively, were documented (all P ≤ 0.001). Of 5 patients demonstrating LVEF ≤ 50% at baseline, all recovered to above this threshold in convalescence. A total of 18 (90%) patients showed persistence of abnormal LGE although mean fibrosis burden was < 5% of LV mass in 85% of cases. No patient experienced major clinical outcomes. CONCLUSIONS: COVID-19 mRNA vaccine-associated myocarditis showed rapid improvements in CMR-based markers of edema, contractile function, and global LGE burden beyond 3 months of recovery in this young patient cohort. However, regional fibrosis following edema resolution was commonly observed, justifying need for ongoing surveillance.

Spike-based adenovirus vectored COVID-19 vaccine does not aggravate heart damage after ischemic injury in mice.

An unprecedented number of COVID-19 vaccination campaign are under way worldwide. The spike protein of SARS-CoV-2, which majorly binds to the host receptor angiotensin converting enzyme 2 (ACE2) for cell entry, is used by most of the vaccine as antigen. ACE2 is highly expressed in the heart and has been reported to be protective in multiple organs. Interaction of spike with ACE2 is known to reduce ACE2 expression and affect ACE2-mediated signal transduction. However, whether a spike-encoding vaccine will aggravate myocardial damage after a heart attack via affecting ACE2 remains unclear. Here, we demonstrate that cardiac ACE2 is up-regulated and protective after myocardial ischemia/reperfusion (I/R). Infecting human cardiac cells or engineered heart tissues with a spike-based adenovirus type-5 vectored COVID-19 vaccine (AdSpike) does not affect their survival and function, whether subjected to hypoxia-reoxygenation injury or not. Furthermore, AdSpike vaccination does not aggravate heart damage in wild-type or humanized ACE2 mice after I/R injury, even at a dose that is ten-fold higher as used in human. This study represents the first systematic evaluation of the safety of a leading COVID-19 vaccine under a disease context and may provide important information to ensure maximal protection from COVID-19 in patients with or at risk of heart diseases.

Could red cell distribution width be used for predicting cardiac injury in neonates with COVID-19?

BACKGROUND: Coronavirus disease 2019 (COVID-19) can affect people of all age groups and it can occasionally cause life-threatening clinical illnesses in immunologically immature populations, especially in newborns. High red cell distribution width (RDW) values were used as an early prognostic biomarker of some neonatal diseases. We aimed to determine the prognostic value of RDW in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infected neonates. METHODS: Newborns with positive SARS-CoV-2 polymerase chain reaction (PCR) test from a nasopharyngeal swab sample, who had refractory fever (>38°C and lasting more than 24 h during hospitalization), were screened for multisystem inflammatory syndrome in newborns (MIS-N), systemic inflammatory indexes calculated and cardiologic evaluations. Due to troponin levels (high: >45 ng/L and low: ≤45 ng/L) patients were grouped. RESULTS: Out of the 68 SARS-CoV-2 PCR-positive newborns, 26 patients had refractory fever. Comparison of laboratory findings between the high and low-troponin groups showed that RDW and neutrophil/lymphocyte ratio values were significantly higher in patients with high troponin levels (p = 0.022 and p = 0.030, respectively). The cut-off values with optimal sensitivity and specificity were determined as 1.00 for neutrophil/lymphocyte ratio (p = 0.205) and 16.6 for RDW (p = 0.014). None of the patients died. CONCLUSIONS: Neonatal COVID-19 generally has a benign prognosis, but can progress to severe disease and cases of MIS-N are rare. RDW could be prognostic in the diagnosis and management of neonates with SARS-CoV-2 infection with high troponin levels.

Cardiopulmonary predictors of mortality in patients with COVID-19: What are the findings?

BACKGROUND: Since 2019, coronavirus disease 2019 (COVID-19) has been the leading cause of mortality worldwide. AIMS: To determine independent predictors of mortality in COVID-19, and identify any associations between pulmonary disease severity and cardiac involvement. METHODS: Clinical, laboratory, electrocardiography and computed tomography (CT) imaging data were collected from 389 consecutive patients with COVID-19. Patients were divided into alive and deceased groups. Independent predictors of mortality were identified. Kaplan-Meier analysis was performed, based on patients having a troponin concentration>99th percentile (cardiac injury) and a CT severity score ≥18. RESULTS: The mortality rate was 29.3%. Cardiac injury (odds ratio [OR] 2.19, 95% confidence interval [CI] 1.14-4.18; P=0.018), CT score ≥18 (OR 2.24, 95% CI 1.15-4.34; P=0.017), localized ST depression (OR 3.77, 95% CI 1.33-10.67; P=0.012), hemiblocks (OR 3.09, 95% CI 1.47-6.48; P=0.003) and history of leukaemia/lymphoma (OR 3.76, 95% CI 1.37-10.29; P=0.010) were identified as independent predictors of mortality. Additionally, patients with cardiac injury and CT score ≥ 18 were identified to have a significantly shorter survival time (mean 14.21 days, 95% CI 10.45-17.98 days) than all other subgroups. There were no associations between CT severity score and electrocardiogram or cardiac injury in our results. CONCLUSIONS: Our findings suggest that using CT imaging and electrocardiogram characteristics together can provide a better means of predicting mortality in patients with COVID-19. We identified cardiac injury, CT score ≥18, presence of left or right hemiblocks on initial electrocardiogram, localized ST depression and history of haematological malignancies as independent predictors of mortality in patients with COVID-19.