NT-proBNP Levels Following IVIG Treatment of Multisystem Inflammatory Syndrome in Children.

BACKGROUND AND OBJECTIVES: N-terminal of probrain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) levels are often elevated in multisystem inflammatory syndrome in children (MIS-C) secondary to inflammation, myocardial dysfunction, or increased wall tension. Intravenous immunoglobulin (IVIG), accepted treatment of MIS-C, may transiently increase myocardial tension and contribute to an increase in NT-proBNP. We sought to study the association between pre- and post-IVIG levels of NT-proBNP and CRP and their clinical significance. METHODS: This single-center, retrospective, cohort study included consecutive children, aged ≤21 years, with diagnosis of MIS-C who received IVIG from April 2020 to October 2021. Data collection included clinical characteristics, laboratory tests, management, and outcomes. Study cohort consisted of patients who received IVIG and had NT-proBNP levels available pre- and post-IVIG. RESULTS: Among 35 patients with MIS-C, 30 met inclusion criteria. Twenty-four, 80%, showed elevation in NT-proBNP post-IVIG. The median NT-proBNP level pre-IVIG was 1921 pg/mL (interquartile range 548-3956), significantly lower than the post-IVIG median of 3756 pg/mL (interquartile range 1342-7634)) (P = .0010). The median pre-IVIG CRP level was significantly higher than the post-IVIG level (12 mg/dL vs 8 mg/dL, P = .0006). All but 1 recovered before discharge, and none had signs of worsening cardiac function post-IVIG. In those who recovered, NT-proBNP had normalized by discharge or 1-week follow-up. CONCLUSIONS: Our study shows that NT-proBNP levels often transiently increase immediately after IVIG therapy without signs of worsening myocardial function. These values should be interpreted in the context of CRP levels and clinical recovery.

[Troponin-T and n-terminal pro-brain type natriuretic peptide plasma levels and its relationship with mortality in COVID-19]. / Niveles plasmáticos de troponina T y de la fracción aminoterminal del propéptido natriurético cerebral y su relación con mortalidad en COVID-19.

INTRODUCTION: Cardiovascular compromise in coronavirus disease 2019 (COVID-19) does not necessarily present with the classic symptoms described in myocarditis. There is growing evidence demonstrating subclinical cardiovascular compromise in the context of the intense inflammation unleashed, the cytokine storm involved, the baseline prothrombotic state, and the consequent endothelial dysfunction. We set out to analyse whether Troponin-T (TT) and the amino-terminal fraction of pro-brain natriuretic peptide (NT-proBNP) determined at hospital admission, are related to mortality during the hospitalization of these patients. MATERIAL AND METHODS: Analytical, observational, retrospective cohort and cross-sectional study. It included subjects with COVID-19 hospitalized for moderate-severe illness, from 20/03/20 to 15/11/20. The TT and NT-proBNP obtained in the first 24 hours from admission were analysed. Altered TT was considered if ≥.014 ng/dl and altered NT-proBNP if ≥300 pg/ml. RESULTS: One hundred and eight subjects were included, 63.2% men, age 51.5 years (59-43), 28% were admitted to the Critical Unit and 25% died. The group with elevated TT presented higher mortality (OR = 3.1; 95%CI = 1.10-8.85; p = .02). The group with elevated NT-proBNP also show higher mortality (OR = 3.47; 95%CI = 1.21-9.97; p = .01). On multivariate analysis, only NT-proBNP ≥300 pg/ml remained an independent risk factor. CONCLUSIONS: NT-proBNP levels ≥300 pg/ml at admission in patients with moderate-severe COVID-19 were associated with higher mortality.

Role of a lower cutoff of high sensitivity troponin I in identification of early cardiac damage in non-severe patients with COVID-19.

Cardiac damage in non-severe patients with coronavirus disease 2019 (COVID-19) is poorly explored. This study aimed to explore the manifestations of cardiac damage at presentation in non-severe patients with COVID-19. In this study, 113 non-severe patients with COVID-19 were grouped according to the duration from symptoms onset to hospital admission: group 1 (≤ 1 week, n = 27), group 2 (> 1 to 2 weeks, n = 28), group 3 (> 2 to 3 weeks, n = 27), group 4 (> 3 weeks, n = 31). Clinical, cardiovascular, and radiological data on hospital admission were compared across the four groups. The level of high sensitivity troponin I (hs-cTnI) in group 2 [10.25 (IQR 6.75-15.63) ng/L] was significantly higher than those in group 1 [1.90 (IQR 1.90-8.80) ng/L] and group 4 [1.90 (IQR 1.90-5.80) ng/L] (all Pbonferroni < 0.05). The proportion of patients who had a level of hs-cTnI ≥ 5 ng/L in group 2 (85.71%) was significantly higher than those in the other three groups (37.04%, 51.85%, and 25.81%, respectively) (all Pbonferroni < 0.05). Compared with patients with hs-cTnI under 5 ng/L, those with hs-cTnI ≥ 5 ng/L had lower lymphocyte count (P = 0.000) and SpO2 (P = 0.002) and higher CRP (P = 0.000). Patients with hs-cTnI ≥ 5 ng/L had a higher incidence of bilateral pneumonia (P = 0.000) and longer hospital length of stay (P = 0.000). In conclusion, non-severe patients with COVID-19 in the second week after symptoms onset were most likely to suffer cardiac damage. A detectable level of hs-cTnI ≥ 5 ng/L might be a manifestation of early cardiac damage in the patients.

Current Use of Cardiac Biomarkers in Various Heart Conditions.

Biomarkers are increasingly recognized to have significant clinical value in early identification and progression of various cardiovascular diseases. There are many heart conditions, such as congestive heart failure (CHF), ischemic heart diseases (IHD), and diabetic cardiomyopathy (DCM), and cardiac remodeling, in which the severity of the cardiac pathology can be mirrored through these cardiac biomarkers. From the emergency department (ED) evaluation of acute coronary syndromes (ACS) or suspected acute myocardial infarction (AMI) with cardiac marker Troponin to the diagnosis of chronic conditions like Heart Failure (HF) with natriuretic peptides, like B-type natriuretic peptide (BNP), N-terminal pro-B- type natriuretic peptide (Nt-proBNP) and mid regional pro-atrial natriuretic peptide (MR- proANP), their use is continuously increasing. Their clinical importance has led to the discovery of newer biomarkers, such as the soluble source of tumorigenicity 2 (sST2), galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15), and various micro ribonucleic acids (miRNAs). Since cardiac pathophysiology involves a complex interplay between inflammatory, genetic, neurohormonal, and biochemical levels, these biomarkers could be enzymes, hormones, and biologic substances showing cardiac injury, stress, and malfunction. Therefore, multi-marker approaches with different combinations of novel cardiac biomarkers, and continual assessment of cardiac biomarkers are likely to improve cardiac risk prediction, stratification, and overall patient wellbeing. On the other hand, these biomarkers may reflect coexisting or isolated disease processes in different organ systems other than the cardiovascular system. Therefore, knowledge of cardiac biomarkers is imperative. In this article, we have reviewed the role of cardiac biomarkers and their use in the diagnosis and prognosis of various cardiovascular diseases from different investigations conducted in recent years.

N-Terminal Pro-B-Type Natriuretic Peptide as a Biomarker for the Severity and Outcomes With COVID-19 in a Nationwide Hospitalized Cohort.

Background Currently, there is limited research on the prognostic value of NT-proBNP (N-terminal pro-B-type natriuretic peptide) as a biomarker in COVID-19. We proposed the a priori hypothesis that an elevated NT-proBNP concentration at admission is associated with increased in-hospital mortality. Methods and Results In this prospective, observational cohort study of the American Heart Association's COVID-19 Cardiovascular Disease Registry, 4675 patients hospitalized with COVID-19 were divided into normal and elevated NT-proBNP cohorts by standard age-adjusted heart failure thresholds, as well as separated by quintiles. Patients with elevated NT-proBNP (n=1344; 28.7%) were older, with more cardiovascular risk factors, and had a significantly higher rate of in-hospital mortality (37% versus 16%; P<0.001) and shorter median time to death (7 versus 9 days; P<0.001) than those with normal values. Analysis by quintile of NT-proBNP revealed a steep graded relationship with mortality (7.1%-40.2%; P<0.001). NT-proBNP was also associated with major adverse cardiac events, intensive care unit admission, intubation, shock, and cardiac arrest (P<0.001 for each). In subgroup analyses, NT-proBNP, but not prior heart failure, was associated with increased risk of in-hospital mortality. Adjusting for cardiovascular risk factors with presenting vital signs, an elevated NT-proBNP was associated with 2-fold higher adjusted odds of death (adjusted odds ratio [OR], 2.23; 95% CI, 1.80-2.76), and the log-transformed NT-proBNP with other biomarkers projected a 21% increased risk of death for each 2-fold increase (adjusted OR, 1.21; 95% CI, 1.08-1.34). Conclusions Elevated NT-proBNP levels on admission for COVID-19 are associated with an increased risk of in-hospital mortality and other complications in patients with and without heart failure.

A close-up view of dynamic biomarkers in the setting of COVID-19: Striking focus on cardiovascular system.

Based on the recent reports, cardiovascular events encompass a large portion of the mortality caused by the COVID-19 pandemic, which drawn cardiologists into the management of the admitted ill patients. Given that common laboratory values may provide key insights into the illness caused by the life-threatening SARS-CoV-2 virus, it would be more helpful for screening, clinical management and on-time therapeutic strategies. Commensurate with these issues, this review article aimed to discuss the dynamic changes of the common laboratory parameters during COVID-19 and their association with cardiovascular diseases. Besides, the values that changed in the early stage of the disease were considered and monitored during the recovery process. The time required for returning biomarkers to basal levels was also discussed. Finally, of particular interest, we tended to abridge the latest updates regarding the cardiovascular biomarkers as prognostic and diagnostic criteria to determine the severity of COVID-19.

A comparative study of IL-6, CRP and NT-proBNP levels in post-COVID multisystem inflammatory syndrome in children (MISC) and Kawasaki disease patients.

BACKGROUND: Post-COVID multisystem hyperinflammatory syndrome in children (MISC) has clinical and laboratory similarities with Kawasaki disease (KD). Inflammatory markers like C-reactive protein (CRP), interleukin 6 (IL6) as well as N-terminal probrain natriuretic peptide (NT-proBNP) are elevated in both. This study attempts a comparative analysis of the 3 markers in an attempt at early differentiation for planning appropriate management. METHODOLOGY: This analytical study conducted at the Institute of Child Health, Kolkata, India compared the levels of the above 3 markers at admission between 72 patients with KD, 30% of whom had coronary artery lesions (CALs) collected over a period of 18 months (Jan 2017-June 2018), with 71 MISC patients over a period of 6 months (July 2020-December 2020). The non-parametric Mann-Whitney U test was used to test for similarity in distributions of the samples of CRP, NT-proBNP and IL6 in KD and MISC patients using correction factor for similar ranks. The 3 parameters were compared using receiver operating characteristic (ROC) curve analysis. RESULTS: Mean IL6 value in KD was 83.22 pg/mL and in MISC 199.91 pg/mL, which was not found to be statistically significant (P = .322 > .05).However mean NT-proBNP (914.91 pg/mL) with CRP level (96.32 mg/L) in KD was significantly lower (P < .05 for both cases) than that in MISC (9141.16 pg/mL and 145.66 mg/L respectively). ROC analysis showed NT-proBNP has the best sensitivity and specificity in predicting MISC. CONCLUSION: NT-proBNP and CRP are significantly higher among MISC patients; ROC analysis shows levels >935.7 pg/mL and >99.55 mg/L respectively might act as a guide to differentiate between them.

Heart failure in type 2 diabetes: current perspectives on screening, diagnosis and management.

Type 2 diabetes is one of the most relevant risk factors for heart failure, the prevalence of which is increasing worldwide. The aim of the review is to highlight the current perspectives of the pathophysiology of heart failure as it pertains to type 2 diabetes. This review summarizes the proposed mechanistic bases, explaining the myocardial damage induced by diabetes-related stressors and other risk factors, i.e., cardiomyopathy in type 2 diabetes. We highlight the complex pathology of individuals with type 2 diabetes, including the relationship with chronic kidney disease, metabolic alterations, and heart failure. We also discuss the current criteria used for heart failure diagnosis and the gold standard screening tools for individuals with type 2 diabetes. Currently approved pharmacological therapies with primary use in type 2 diabetes and heart failure, and the treatment-guiding role of NT-proBNP are also presented. Finally, the influence of the presence of type 2 diabetes as well as heart failure on COVID-19 severity is briefly discussed.

Effect of Treatment With Sacubitril/Valsartan in Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

Importance: The use of sacubitril/valsartan is not endorsed by practice guidelines for use in patients with New York Heart Association class IV heart failure with a reduced ejection fraction because of limited clinical experience in this population. Objective: To compare treatment with sacubitril/valsartan treatment with valsartan in patients with advanced heart failure and a reduced ejection fraction and recent New York Heart Association class IV symptoms. Design, Setting, and Participants: A double-blind randomized clinical trial was conducted; a total of 335 patients with advanced heart failure were included. The trial began on March 2, 2017, and was stopped early on March 23, 2020, owing to COVID-19 risk. Intervention: Patients were randomized to receive sacubitril/valsartan (target dose, 200 mg twice daily) or valsartan (target dose, 160 mg twice daily) in addition to recommended therapy. Main Outcomes and Measures: The area under the curve (AUC) for the ratio of N-terminal pro-brain natriuretic peptide (NT-proBNP) compared with baseline measured through 24 weeks of therapy. Results: Of the 335 patients included in the analysis, 245 were men (73%); mean (SD) age was 59.4 (13.5) years. Seventy-two eligible patients (18%) were not able to tolerate sacubitril/valsartan, 100 mg/d, during the short run-in period, and 49 patients (29%) discontinued sacubitril/valsartan during the 24 weeks of the trial. The median NT-proBNP AUC for the valsartan treatment arm (n = 168) was 1.19 (IQR, 0.91-1.64), whereas the AUC for the sacubitril/valsartan treatment arm (n = 167) was 1.08 (IQR, 0.75-1.60). The estimated ratio of change in the NT-proBNP AUC was 0.95 (95% CI 0.84-1.08; P = .45). Compared with valsartan, treatment with sacubitril/valsartan did not improve the clinical composite of number of days alive, out of hospital, and free from heart failure events. Aside from a statistically significant increase in non-life-threatening hyperkalemia in the sacubitril/valsartan arm (28 [17%] vs 15 [9%]; P = .04), there were no observed safety concerns. Conclusions and Relevance: The findings of this trial showed that, in patients with chronic advanced heart failure with a reduced ejection fraction, there was no statistically significant difference between sacubitril/valsartan and valsartan with respect to reducing NT-proBNP levels. Trial Registration: ClinicalTrials.gov Identifier: NCT02816736.

Paediatric post-COVID-19 hyperinflammatory syndrome mimicking appendicitis: a case series.

INTRODUCTION: A novel hyperinflammatory syndrome has emerged in the paediatric population: paediatric inflammatory multisystem syndrome - temporally associated with SARS-CoV-2 (PIMS-TS). Up to 50% of patients develop shock with cardiac dysfunction but presentation with acute abdominal pain is common and difficult to distinguish from appendicitis. METHOD: Prospective case series of PIMS-TS patients presenting to a single UK tertiary paediatric centre. RESULTS: As of 16 September 2020, 89 patients have presented with PIMS-TS to our institution; 19 (21.3%) were referred for surgical review. Pyrexia and acute abdominal pain were seen in all 19 patients. Diarrhoea was reported in 14 (73%) and vomiting in 12 (63%). On examination, eight (42%) had right abdominal tenderness, of which five had right iliac fossa (RIF) peritonism. C-reactive protein (CRP) was universally raised: median 176 (15-463)mg/l. Abdominal imaging was performed in 17 (89%), with 11 undergoing abdominal ultrasonography (65%) and 8 abdominal computed tomography (47%); two required both. Findings included nonspecific features of inflammation in the RIF. Eight patients (42%) had an abnormal echocardiogram at admission. Two (10%) patients, with classical signs and symptoms of appendicitis, underwent appendicectomy without radiological imaging and were subsequently diagnosed with PIMS-TS. During the same period, 18 patients underwent appendicectomy for histologically confirmed appendicitis. Serum CRP and ferritin levels were significantly higher in the PIMS-TS cohort compared with children with appendicitis. CONCLUSIONS: PIMS-TS is a novel paediatric condition that may mimic appendicitis. It should be considered in patients presenting with abdominal pain to avoid unnecessary surgery in children at risk of cardiovascular instability.

ST-elevation in an adolescent with COVID-19: Myopericarditis or myocardial infarction?

Myocardial infarctions (MI) have been reported in adults with COVID-19. Although MIs are rare in children with COVID-19, cardiac involvement is still possible. In this case report, we present an adolescent with recent COVID-19 infection who presented with an ECG initially suggestive of myocardial infarction (MI). We describe how to differentiate between myocardial infarctions and myopericarditis. A 15-year-old boy, with a history of COVID-19 infection a month prior, presented to the emergency department with fever, abdominal pain, diarrhea, and chest pain. On ECG, he was found to have focal ST-segment elevations in V3 through V6. Given the immediate concern for MI, an emergent echocardiogram was done and showed normal left ventricular systolic function with no regional dyskinesia and normal coronary artery diameters. A repeat ECG showed diffuse ST elevations in the inferior leads and T-wave inversions on V5 and V6, confirming the diagnosis of myopericarditis. In conclusion, multisystem-inflammatory syndrome in children associated with COVID-19 (MIS-C) is a new entity describing a post-infectious inflammatory response in children with prior COVID-19 exposure. Cardiac involvement can include myopericarditis. Initial ECGs may show ST-changes suggestive of MI. However, serial ECGs and echocardiograms can differentiate between MI and myocarditis/myopericarditis. Even with COVID-19, MIs are extremely rare in children, and it is important to be aware of MIS-C and its cardiac complications.

Cardiac pathology 6 months after hospitalization for COVID-19 and association with the acute disease severity.

BACKGROUND: Coronavirus disease 2019 (COVID-19) may cause myocardial injury and myocarditis, and reports of persistent cardiac pathology after COVID-19 have raised concerns of long-term cardiac consequences. We aimed to assess the presence of abnormal cardiovascular resonance imaging (CMR) findings in patients recovered from moderate-to-severe COVID-19, and its association with markers of disease severity in the acute phase. METHODS: Fifty-eight (49%) survivors from the prospective COVID MECH study, underwent CMR median 175 [IQR 105-217] days after COVID-19 hospitalization. Abnormal CMR was defined as left ventricular ejection fraction (LVEF) <50% or myocardial scar by late gadolinium enhancement. CMR indices were compared to healthy controls (n = 32), and to circulating biomarkers measured during the index hospitalization. RESULTS: Abnormal CMR was present in 12 (21%) patients, of whom 3 were classified with major pathology (scar and LVEF <50% or LVEF <40%). There was no difference in the need of mechanical ventilation, length of hospital stay, and vital signs between patients with vs without abnormal CMR after 6 months. Severe acute respiratory syndrome coronavirus 2 viremia and concentrations of inflammatory biomarkers during the index hospitalization were not associated with persistent CMR pathology. Cardiac troponin T and N-terminal pro-B-type natriuretic peptide concentrations on admission, were higher in patients with CMR pathology, but these associations were not significant after adjusting for demographics and established cardiovascular disease. CONCLUSIONS: CMR pathology 6 months after moderate-to-severe COVID-19 was present in 21% of patients and did not correlate with severity of the disease. Cardiovascular biomarkers during COVID-19 were higher in patients with CMR pathology, but with no significant association after adjusting for confounders. TRIAL REGISTRATION: COVID MECH Study ClinicalTrials.gov Identifier: NCT04314232.

Admission NT-proBNP and outcomes in patients without history of heart failure hospitalized with COVID-19.

AIMS: We examined the value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients admitted for coronavirus disease 2019 (COVID-19) without prior history of heart failure (HF) or cardiomyopathy. METHODS AND RESULTS: Retrospective cohort of consecutive adults (N = 679; median age 59 years; 38.7% women; 87.5% White; 7.1% Black; 5.4% Asian; 34.3% Hispanic) admitted with documented COVID-19 in an academic centre in Long Island, NY. Admission NT-proBNP was categorized using the European Society of Cardiology Heart Failure Association age-specific criteria for acute presentations. We examined (i) mortality and the composite of death or mechanical ventilation and (ii) out-of-hospital, intensive care unit (ICU)-free, and ventilator-free days at 28 days. Estimates were adjusted for confounders using a lasso selection process. Using age-specific criteria, 417 patients (61.4%) had low, 141 (20.8%) borderline, and 121 (17.8%) high NT-proBNP. Mortality was 5.8%, 20.6%, and 36.4% for patients with low, borderline, and high NT-proBNP, respectively. In lasso-adjusted models, high NT-proBNP was associated with higher mortality [hazard ratio (HR) 2.15; 95% confidence interval (CI) 1.06-4.39; P = 0.034] and composite endpoint rates (HR 1.66; 95%CI 1.04-2.66; P = 0.035). Patients with high NT-proBNP had 32%, 33%, and 33% fewer out-of-hospital, ICU-free, and ventilator-free days compared with low NT-proBNP counterparts. Results were consistent across age, sex, and race, and regardless of coronary artery disease or hypertension, except for stronger mortality signal with high NT-proBNP in women. CONCLUSIONS: In patients with COVID-19 and no HF history, high admission NT-proBNP is associated with higher mortality and healthcare resources utilization. Preventive strategies may be required for these patients.

Predictive value of cardiac markers in the prognosis of COVID-19 in children.

BACKGROUND AND AIM: Occasionally, children with COVID-19 may develop arrhythmia, myocarditis, and cardiogenic shock involving multisystemic inflammatory syndrome in children (MIS-C). This study aimed to identify the laboratory parameters that may predict early cardiovascular involvement in these patients. MATERIALS AND METHODS: Data of 320 pediatric patients, aged 0-18 years (average age, 10.46 ± 5.77 years; 156 female), with positive COVID-19 reverse transcription-polymerase chain reaction test and with cardiac biomarkers at the time of admission to the pediatric emergency department were retrospectively scanned. The age, sex, COVID-19-associated symptoms, pro-brain natriuretic peptide (proBNP), CK-MB, and troponin I levels of the patients were recorded. RESULTS: Fever was noted in 58.1% of the patients, cough in 29.7%, diarrhea in 7.8%, headache in 14.7%, sore throat in 17.8%, weakness in 17.8%, abdominal pain in 5%, loss of taste in 4.1%, loss of smell in 5.3%, nausea in 3.4%, vomiting in 3.8%, nasal discharge in 4.4%, muscle pain in 5%, and loss of appetite in 3.1%. The proBNP value ≥282 ng/L predicted the development of MIS-C with 100% sensitivity and 93% specificity [AUC: 0.985 (0.959-1), P < 0.001]; CK-MB value ≥2.95 with 80% sensitivity and 77.6% specificity [AUC: 0.792 (0.581-1), P = 0.026]; and troponin I value ≥0.03 with 60% sensitivity and 99.2% specificity [AUC: 0.794 (0.524-1)]. CONCLUSIONS: Cardiac markers (proBNP and troponin I), especially proBNP, could be used to detect early diagnosis of cardiac involvement and/or MIS-C in pediatric patients with COVID-19 and to predict related morbidity and mortality.

Prognostic parameters of in-hospital mortality in COVID-19 patients-An Italian experience.

Background During COVID-19 outbreak, Italy was the first country in Europe to be heavily affected with an intensive care unit mortality of 26%. In order to reduce this percentage, physicians should establish clear and objective criteria to stratify COVID-19 patients at high risk of in-hospital death. Thus, the aim has been to test a large spectrum of variables ranging from clinical evaluation to laboratory biomarkers to identify which parameter would best predict all-cause in-hospital mortality in COVID-19 patients. Design observational study. Results Multivariate Cox regression analysis showed that each 5 years of increase in age corresponded to a hazard ratio (HR) of 1.28 (95% CI 1.00-1.65, P = .050); each increment of 803 ng/L of N-terminal pro-B-type natriuretic peptide (NT-proBNP) corresponded to a HR of 1.24 (95% CI 1.11-1.39, P < .001); each increment of 58 ng/L of interleukin (IL)-6 corresponded to a HR of 1.23 (95% CI 1.09-1.40, P < .001), and each increment of 250 U/L of lactate dehydrogenase (LDH) corresponded to a HR of 1.23 (95% CI 1.10-1.37, P < .001). According to the calculated cut-points for age (≥70 years), NT-proBNP (≥803 ng/L), IL-6 (≥58 ng/L) and LDH (≥371 U/L) when 2 out of these 4 were overcome, the HR was 2.96 (95% CI 1.97-4.45, P < .001). Conclusion In COVID-19 patients, besides age, the evaluation of three biochemical parameters, available in few hours after hospital admission can predict in-hospital mortality regardless of other comorbidities.

Troponin and Other Biomarker Levels and Outcomes Among Patients Hospitalized With COVID-19: Derivation and Validation of the HA2T2 COVID-19 Mortality Risk Score.

Background The independent prognostic value of troponin and other biomarker elevation among patients with coronavirus disease 2019 (COVID-19) are unclear. We sought to characterize biomarker levels in patients hospitalized with COVID-19 and develop and validate a mortality risk score. Methods and Results An observational cohort study of 1053 patients with COVID-19 was conducted. Patients with all of the following biomarkers measured-troponin-I, B-type natriuretic peptide, C-reactive protein, ferritin, and d-dimer (n=446) -were identified. Maximum levels for each biomarker were recorded. The primary end point was 30-day in-hospital mortality. Multivariable logistic regression was used to construct a mortality risk score. Validation of the risk score was performed using an independent patient cohort (n=440). Mean age of patients was 65.0±15.2 years and 65.3% were men. Overall, 444 (99.6%) had elevation of any biomarker. Among tested biomarkers, troponin-I ≥0.34 ng/mL was the only independent predictor of 30-day mortality (adjusted odds ratio, 4.38; P<0.001). Patients with a mortality score using hypoxia on presentation, age, and troponin-I elevation, age (HA2T2) ≥3 had a 30-day mortality of 43.7% while those with a score <3 had mortality of 5.9%. Area under the receiver operating characteristic curve of the HA2T2 score was 0.834 for the derivation cohort and 0.784 for the validation cohort. Conclusions Elevated troponin and other biomarker levels are commonly seen in patients hospitalized with COVID-19. High troponin levels are a potent predictor of 30-day in-hospital mortality. A simple risk score can stratify patients at risk for COVID-19-associated mortality.

Characteristics and impact of cardiovascular comorbidities on coronavirus disease 2019 in women: A multicentre cohort study.

BACKGROUND: Although women account for up to half of patients hospitalized for coronavirus disease 2019 (COVID-19), no specific data have been reported in this population. AIMS: To assess the burden and impact of cardiovascular comorbidities in women with COVID-19. METHODS: All consecutive patients hospitalized for COVID-19 across 24 hospitals from 26 February to 20 April 2020 were included. The primary composite outcome was transfer to an intensive care unit or in-hospital death. RESULTS: Among 2878 patients, 1212 (42.1%) were women. Women were older (68.3±18.0 vs. 65.4±16.0 years; P<0.001), but had less prevalent cardiovascular comorbidities than men. Among women, 276 (22.8%) experienced the primary outcome, including 161 (13.3%) transfers to an intensive care unit and 115 (9.5%) deaths without transfer to intensive care unit. The rate of in-hospital death or transfer to an intensive care unit was lower in women versus men (crude hazard ratio [HR]: 0.62, 95% confidence interval [CI]: 0.53-0.72). Age (adjusted HR: 1.05 per 5-year increase, 95% CI: 1.01-1.10), body mass index (adjusted HR: 1.06 per 2-unit increase, 95% CI: 1.02-1.10), chronic kidney disease (adjusted HR: 1.57, 95% CI: 1.11-2.22) and heart failure (adjusted HR: 1.52, 95% CI: 1.04-2.22) were independently associated with the primary outcome in women. Elevated B-type natriuretic peptide/N-terminal prohormone of B-type natriuretic peptide (adjusted HR: 2.41, 95% CI: 1.70-3.44) and troponin (adjusted HR: 2.00, 95% CI: 1.39-2.88) concentrations at admission were also associated with the primary outcome, even in women free of previous coronary artery disease or heart failure. CONCLUSIONS: Although female sex was associated with a lower risk of transfer to an intensive care unit or in-hospital death, COVID-19 remained associated with considerable morbimortality in women, especially in those with cardiovascular diseases.

Cardiac markers of multisystem inflammatory syndrome in children (MIS-C) in COVID-19 patients: A meta-analysis.

OBJECTIVE: A meta-analysis of laboratory cardiac markers for multisystem inflammatory syndrome in children (MIS-C) was performed in patients with coronavirus disease 2019 (COVID-19). METHODS: Eight databases were searched until April 10, 2021, for studies on cardiac markers, including B-type natriuretic peptide (BNP)/N-terminal pro-BNP (NT-proBNP), troponin, aspartate aminotransferase (AST), in MIS-C patients. RESULTS: Of the 2583 participants enrolled in 24 studies, 1613 patients were diagnosed with MIS-C. MIS-C patients exhibited higher BNP levels than patients with non-severe COVID-19 [SMD (95% CI): 1.13 (0.48, 1.77), p < 0.05]. No significant differences in BNP levels were observed between patients with MIS-C and severe COVID-19 [SMD (95% CI): 0.29 (-0.07, 0.65), p = 0.117]. Comparisons of MIS-C patients to all COVID-19 patients revealed no significant differences in levels of troponin [SMD (95% CI): 0.13 (-0.07, 0.32), p = 0.212] or AST [SMD (95% CI): 0.10 (-0.11, 0.31), p = 0.336]. Compared to patients with non-severe MIS-C, those with severe MIS-C exhibited higher levels of BNP [SMD (95% CI): 0.26 (0.04, 0.48), p < 0.05], but no differences in troponin [SMD (95% CI): 0.05 (-0.06, 0.16) p = 0.387] or AST [SMD (95% CI): 0.19 (-0.34, 0.71), p = 0.483] were observed. Moreover, there was no significant difference in BNP [SMD (95% CI): -0.21 (-1.07, 0.64), p = 0.624] or troponin [SMD (95% CI): -0.07 (-0.45, 0.31), p = 0.710] between MIS-C with and without coronary artery abnormality. Sensitivity analyses were performed to assess stability. No publication bias was detected based on Begg's test. CONCLUSIONS: The key cardiac marker that showed differences between patients with MIS-C/non-severe COVID-19 and between patients with severe/non-severe MIS-C was BNP. Other markers, such as troponin and AST, did not exhibit notable differences in indicating cardiac injury between patients with MIS-C and COVID-19.