Natriuretic Peptides as Biomarkers: Narrative Review and Considerations in Cardiovascular and Respiratory Dysfunctions.

Natriuretic peptides (NPs) encompass a family of structurally related hormone/paracrine factors acting through the natriuretic peptide system regulating cell proliferation, vessel tone, inflammatory processes, neurohumoral pathways, fluids, and electrolyte balance. The three most studied peptides are atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-Type natriuretic peptide (CNP). ANP and BNP are the most relevant NPs as biomarkers for the diagnosis and prognosis of heart failure and underlying cardiovascular diseases, such as cardiac valvular dysfunction, hypertension, coronary artery disease, myocardial infarction, persistent arrhythmias, and cardiomyopathies. Cardiac dysfunctions related to cardiomyocytes stretching in the atria and ventricles are primary elicitors of ANP and BNP release, respectively. ANP and BNP would serve as biomarkers for differentiating cardiac versus noncardiac causes of dyspnea and as a tool for measuring the prognosis of patients with heart failure; nevertheless, BNP has been shown with the highest predictive value, particularly related to pulmonary disorders. Plasma BNP has been reported to help differentiate cardiac from pulmonary etiologies of dyspnea in adults and neonates. Studies have shown that COVID-19 infection also increases serum levels of N-terminal pro b-type natriuretic peptide (NT-proBNP) and BNP. This narrative review assesses aspects of ANP and BNP on their physiology, and predictive values as biomarkers. We present an overview of the NPs' synthesis, structure, storage, and release, as well as receptors and physiological roles. Following, considerations focus on ANP versus BNP, comparing their relevance in settings and diseases associated with respiratory dysfunctions. Finally, we compiled data from guidelines for using BNP as a biomarker in dyspneic patients with cardiac dysfunction, including its considerations in COVID-19.

Comparison of cord blood pro-BNP levels in newborns of SARS-COV-2-positive and -negative women, and its association with adverse perinatal outcomes.

OBJECTIVE: To compare umbilical cord blood pro-B-type natriuretic peptide (BNP) levels in newborns of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) positive pregnancies to those of SARS-COV-2 negative pregnancies. METHODS: Prospectively cord blood samples from newborns of 42 SARS-COV-2 positive women, and 42 negative pregnant were collected at birth and analyzed for pro-BNP levels. RESULTS: The mean cord blood pro-BNP level was significantly higher in newborns of SARS-COV-2 positive women than in controls. Furthermore, the pro-BNP level was an independent predictor of NICU admission in both SARS-COV-2 positive and control patients. CONCLUSION: Cord blood pro-BNP level may be a parameter that can predict the under-stress fetus and adverse perinatal outcomes especially, in cases where placental involvement is present as in SARS-COV-2 infection.

Association between B-type natriuretic peptide and long-term mortality in patients with acute severe hypertension visiting the emergency department.

B-type natriuretic peptide (BNP) is a well-established prognostic factor for cardiovascular disorders. However, the association between BNP levels and mortality in patients with acute severe hypertension remains unclear. This study aimed to investigate the association between BNP levels and long-term mortality in patients with acute severe hypertension visiting the emergency department (ED). This retrospective study included patients aged ≥ 18 years who were admitted to the ED between 2016 and 2019 with acute severe hypertension (systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 100 mmHg). Patients were categorized into tertiles according to BNP levels upon admission to the ED. Of the 3099 patients with acute severe hypertension, 6.4% in the first (lowest) tertile, 24.8% in the second tertile, and 44.4% in the third (highest) tertile of BNP died within 3-years. After adjusting for clinically relevant variables, patients in the second tertile of BNP (adjusted hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.96-3.55), and patients in the third tertile of BNP (adjusted HR 4.18; 95% CI, 3.09-5.64) had a significantly higher risk of 3-year all-cause mortality than those in the first tertile of BNP. Therefore, BNP may be valuable for the initial assessment to identify high-risk patients among those with acute severe hypertension.

Hypoxic pulmonary vascular response can screen subclinical lifestyle disease in healthy population.

OBJECTIVE: Subclinical life style disease can cause endothelial dysfunction associated with perfusion abnormalities and reduced vascular compliance. Subclinical elevated beta type natriuretic peptide (BNP) has been associated with altered fluid shift from extra to intracellular space during acute hypoxia. Therefore we measured vascular response and BNP levels during acute hypoxia to study endothelial functions among healthy individuals. METHODS: Individuals were exposed to acute normobaric hypoxia of FiO2 = 0.15 for one hour in supine position and their pulmonary and systemic vascular response to hypoxia was compared. Individuals were divided into two groups based on either no response (Group 1) or rise in systolic pulmonary artery pressure to hypoxia (Group 2) and their BNP levels were compared. RESULTS: BNP was raised after hypoxia exposure in group 2 only from 18.52 ± 7 to 21.56 ± 10.82 picogram/ml, p < 0.05. Group 2 also showed an increase in mean arterial pressure and no fall in total body water in response to acute hypoxia indicating decreased endothelial function compared to Group 1. CONCLUSION: Rise in pulmonary artery pressure and BNP level in response to acute normobaric hypoxia indicates reduced endothelial function and can be used to screen subclinical lifestyle disease among healthy population.

Admission high-sensitivity cardiac troponin levels as a prognostic indicator for in-hospital mortality rates in the elderly and very elderly COVID-19 patients.

BACKGROUND: Elevation of cardiac troponin (cTn) is associated with the worst prognosis not only in cardiovascular disease but also in non-cardiovascular disease. The aim of this study is to verify if cTn has a prognostic role in elderly and very elderly coronavirus disease 2019 (COVID-19) patients. METHODS: This study enrolled consecutive COVID-19 elderly patients hospitalized at INRCA hospital, with available admission high sensitivity cardiac troponin T (HS-cTnT) level. Patients were divided into three groups based on HS-cTnT level: group A (Hs-cTnT ≤ 40 pg/ml), group B (Hs-cTnT 41-100 pg/ml), and group C (Hs-cTnT ≥ 101 pg/ml). The correlation between HS-cTnT levels and mortality rates was analyzed. RESULTS: 461 patients (mean age 86 years; 59% female) were divided into group A (261 patients), group B (129 patients), and group C (71 patients). Group C resulted significantly older, more affected by heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and dementia, and with higher levels of creatinine, C-reactive protein, pro-calcitonin, interleukin-6, ferritin, NT-proBNP, D-dimer then group A and group B. Mortality rate increased significantly across groups (group A: 18.4%; group B: 36.4%; group C: 62.0%; p<0.001). Group C had a significant increase in mortality risk compared to group A, both univariate analysis (HR 3.78) and multivariate analysis (model 2 HR 3.10; model 3 HR 3.59; model 4 HR 1.72). CONCLUSION: HS-cTnT has demonstrated a prognostic role in elderly and very elderly COVID-19 patients. HS-cTnT is a simple and inexpensive laboratory exam that gives clinicians important information on mortality risk stratification.

The Combination Clinical Value of Plasma Brain Natriuretic Peptide and Serum HbAlc in the Diagnosis of Chronic Pulmonary Heart Disease.

Objective: To analyze the combination clinical value of plasma brain natriuretic peptide and serum glycated hemoglobin (HbAlc) in chronic pulmonary heart disease. Methods: A total of 200 patients with chronic pulmonary heart disease admitted to our hospital from January 2021 to January 2022 were selected as the observation group, and 200 healthy subjects were selected as the control group during the same period. All subjects were examined by an ECG vector map and plasma BNP, and HbAlc levels were detected to analyze the value and clinical significance of each index in single diagnosis and combined diagnosis. Results: Plasma BNP and HbAlc levels in the observation group were significantly higher than those in the control group (P < 0.05). There were 154 BNP positive, 146 HbAlc positive, 164 parallel combined diagnosis positive, and 132 serial combined diagnosis positive. Sensitivity of series combination diagnosis was significantly higher than other indexes (P < 0.05); especially, parallel combination diagnosis was significantly higher than other indexes (P < 0.05). Besides, area under the ROC curve of parallel combination diagnosis and series combination diagnosis was significantly higher than that of each index alone diagnosis (P < 0.05). Conclusion: In the diagnosis of chronic pulmonary heart disease, the combination of plasma BNP and HbAlc can effectively improve the diagnostic specificity and sensitivity, as well as improve the area under the ROC curve.

Elevated Natriuretic Peptides in Patients With Severe or Critical COVID-19: A Meta-Analysis.

BACKGROUND: The worldwide COVID-19 pandemic caused by SARS-CoV-2 has resulted in an extraordinary increase in the number of patients who are severely critically ill. For many of these patients, cardiovascular risk factors are key contributors to the development of severe illness. Laboratory markers for cardiac damage and failure, such as natriuretic peptides, are reported to be elevated in patients with severe COVID-19. METHODS: We conducted a systematic review and meta-analysis to compare natriuretic peptide levels in patients with severe COVID-19 vs those with nonsevere COVID-19. PubMed and medRxiv were searched through April 7, 2020. The outcome of interest was the difference in B-type natriuretic peptide (BNP) or N-terminal-proBNP levels in patients with severe vs nonsevere COVID-19. RESULTS: We identified 9 retrospective cohort studies that had a total of 1,575 patients with COVID-19 who had their natriuretic peptides measured and were classified by disease severity. All studies were conducted in China. Patients with severe COVID-19 had significantly higher BNP levels than patients with nonsevere COVID-19 (mean difference, 69.56 pg/mL; 95% CI, 1.77-137.35 pg/mL; P = .04, I2 = 83%). Similarly, patients with severe COVID-19 had significantly higher N-terminal-proBNP levels than patients with nonsevere COVID-19 (mean difference, 518.65 pg/mL; 95% CI, 152.40-884.90 pg/mL; P = .006, I2 = 86%). CONCLUSIONS: In this study, Chinese patients with severe COVID-19 had higher natriuretic peptide levels than those with nonsevere COVID-19. Studies from all countries affected by the virus will help to further delineate whether the cause is directly or indirectly of cardiac origin and whether preexisting heart failure has an influence on this disparity.

Sex differences in determinants of COVID-19 severe outcomes - findings from the National COVID Cohort Collaborative (N3C).

OBJECTIVE: The impact of comorbidities and biomarkers on COVID-19 severity vary by sex but have not yet been verified in population-based studies. We examined the association of comorbidities, inflammatory biomarkers, and severe outcomes in men and women hospitalized for COVID-19. DESIGN: This is a retrospective cohort analysis based on the National COVID Cohort Collaborative (N3C). We included 574,391 adult patients admitted for COVID-19 at hospitals or emergency rooms between 01/01/2020 and 12/31/2021. METHODS: We defined comorbidities at or before the first admission for COVID-19 by Charlson Comorbidity Index (CCI) and CCI components. We used the averaged lab values taken within 15 days before or after the admission date to measure biomarkers including c-reactive protein (CRP), ferritin, procalcitonin, N-terminal pro b-type natriuretic peptide (NT proBNP), d-dimer, absolute lymphocyte counts, absolute neutrophil counts, and platelets. Our primary outcome was all-cause mortality; secondary outcomes were invasive mechanical ventilation (IMV) and hospital length of stay (LOS). We used logistic regression adjusted for age, race, ethnicity, visit type, and medications to assess the association of comorbidities, biomarkers, and mortality disaggregating by sex. RESULTS: Moderate to severe liver disease, renal disease, metastatic solid tumor, and myocardial infarction were the top four fatal comorbidities among patients who were hospitalized for COVID-19 (adjusted odds ratio [aOR] > 2). These four comorbid conditions remained the most lethal in both sexes, with a higher magnitude of risk in women than in men (p-interaction < 0.05). Abnormal elevations of CRP, ferritin, procalcitonin, NT proBNP, neutrophil, and platelet counts, and lymphocytopenia were significantly associated with the risk of death, with procalcitonin and NT proBNP as the strongest predictors (aOR > 2). The association between the abnormal biomarkers and death was stronger in women than in men (p-interaction < 0.05). CONCLUSION: There are sex differences in inpatient mortality associated with comorbidities and biomarkers. The significant impact of these clinical determinants in women with COVID-19 may be underappreciated as previous studies stressed the increased death rate in male patients that is related to comorbidities or inflammation. Our study highlights the importance and the need for sex-disaggregated research to understand the risk factors of poor outcomes and health disparities in COVID-19.

SARS-COV-ATE risk assessment model for arterial thromboembolism in COVID-19.

Patients with SARS-CoV-2 infection are at an increased risk of cardiovascular and thrombotic complications conferring an extremely poor prognosis. COVID-19 infection is known to be an independent risk factor for acute ischemic stroke and myocardial infarction (MI). We developed a risk assessment model (RAM) to stratify hospitalized COVID-19 patients for arterial thromboembolism (ATE). This multicenter, retrospective study included adult COVID-19 patients admitted between 3/1/2020 and 9/5/2021. Among 3531 patients from the training cohort, 15.5% developed acute in-hospital ATE, including stroke, MI, and other ATE, compared to 13.4% in the validation cohort. The 16-item final score was named SARS-COV-ATE (Sex: male = 1, Age [40-59 = 2, > 60 = 4], Race: non-African American = 1, Smoking = 1 and Systolic blood pressure elevation = 1, Creatinine elevation = 1; Over the range: leukocytes/lactate dehydrogenase/interleukin-6, B-type natriuretic peptide = 1, Vascular disease (cardiovascular/cerebrovascular = 1), Aspartate aminotransferase = 1, Troponin-I [> 0.04 ng/mL = 1, troponin-I > 0.09 ng/mL = 3], Electrolytes derangement [magnesium/potassium = 1]). RAM had a good discrimination (training AUC 0.777, 0.756-0.797; validation AUC 0.766, 0.741-0.790). The validation cohort was stratified as low-risk (score 0-8), intermediate-risk (score 9-13), and high-risk groups (score ≥ 14), with the incidence of ATE 2.4%, 12.8%, and 33.8%, respectively. Our novel prediction model based on 16 standardized, commonly available parameters showed good performance in identifying COVID-19 patients at risk for ATE on admission.

A 14-Year-Old Boy With Neck Pain, Fevers, and Diffuse Erythematous Rash.

A previously healthy 14-year-old boy developed right-sided neck pain, tachycardia, a diffuse erythematous rash, and subjective fevers over 2 days. He sought medical attention in a local urgent care clinic, where he had a negative Sars-CoV-2 antigen test and was referred to the local emergency department (ED) for persistent tachycardia and further workup. After fluid resuscitation, his tachycardia was not improved, so he was admitted to the Pediatric Hospital Medicine Service. Physical examination showed large areas of erythema and erythroderma of multiple body sites, perioral sparing, increased erythema in flexor skin folds, posterior soft palate petechiae, and a white strawberry tongue. There was a small, tender lesion with surrounding erythema without discharge on his right neck thought to be a possible entry point for infection. Laboratory results showed thrombocytopenia, normal white blood cell count, normal hemoglobin concentration, absolute lymphopenia, and an elevated C-reactive protein (CRP) to 130 mg/L. He was started on intravenous fluids and antibiotics for a presumed infectious cause of the rash and laboratory findings. The next morning, an expanded diagnostic workup was undertaken including electrocardiogram, echocardiogram, ferritin, triglycerides, liver enzymes, lactate dehydrogenase (LDH), brain natriuretic peptide, coagulation studies, and fibrinogen. With treatment and supportive care, his tachycardia and energy improved, so he was discharged with oral antibiotics and follow-up with the Infectious Disease Clinic in 2 days. When seen in follow-up, he was immediately admitted to the hospital for worsening fatigue, tachycardia, and new findings that prompted multiple consultations, and transfer to pediatric critical care services.

Myocardial Work in Patients Hospitalized With COVID-19: Relation to Biomarkers, COVID-19 Severity, and All-Cause Mortality.

Background COVID-19 infection has been hypothesized to affect left ventricular function; however, the underlying mechanisms and the association to clinical outcome are not understood. The global work index (GWI) is a novel echocardiographic measure of systolic function that may offer insights on cardiac dysfunction in COVID-19. We hypothesized that GWI was associated with disease severity and all-cause death in patients with COVID-19. Methods and Results In a multicenter study of patients admitted with COVID-19 (n=305), 249 underwent pressure-strain loop analyses to quantify GWI at a median time of 4 days after admission. We examined the association of GWI to cardiac biomarkers (troponin and NT-proBNP [N-terminal pro-B-type natriuretic peptide]), disease severity (oxygen requirement and CRP [C-reactive protein]), and all-cause death. Patients with elevated troponin (n=71) exhibited significantly reduced GWI (1508 versus 1707 mm Hg%; P=0.018). A curvilinear association to NT-proBNP was observed, with increasing NT-proBNP once GWI decreased below 1446 mm Hg%. Moreover, GWI was significantly associated with a higher oxygen requirement (relative increase of 6% per 100-mm Hg% decrease). No association was observed with CRP. Of the 249 patients, 37 died during follow-up (median, 58 days). In multivariable Cox regression, GWI was associated with all-cause death (hazard ratio, 1.08 [95% CI, 1.01-1.15], per 100-mm Hg% decrease), but did not increase C-statistics when added to clinical parameters. Conclusions In patients admitted with COVID-19, our findings indicate that NT-proBNP and troponin may be associated with lower GWI, whereas CRP is not. GWI was independently associated with all-cause death, but did not provide prognostic information beyond readily available clinical parameters. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04377035.

Changes in Some Vascular Biomarkers in Patients with Severe COVID-19 with Various Degrees of Pulmonary Hypertension.

The aim of the study was to evaluate the levels of cardiac biomarkers endothelin 1, B-natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (Nt-proBNP), NO2, and NO3 in patients with COVID-19 pneumonia and various degrees of pulmonary hypertension. Group 1 included patients with pulmonary artery systolic pressure <25 mm Hg, group 2 with 25-40 mm Hg, and group 3 with 40-60 mm Hg. In the group of patients with pulmonary artery systolic pressure <25 mm Hg, the level of NT-proBNP was higher than in the rest two groups by 41.3% (p=0.015) and 38.2% (p=0.015), respectively. The levels of nitrites and nitrates in group 1 patients were lower: NO2 was reduced by 31.1% (p=0.026) and 62.8% (p=0.008), and NO3 was reduced by 28% (p=0.029) and by 54.6% (p=0.006), respectively. No other changes in the parameters in patients receiving oxygen therapy were found. These findings suggest that severe course of COVID-19 in patients with severe pulmonary hypertension is associated with impaired nitrite and nitrate metabolism and reduced levels of Nt-proBNP.

Diagnostic Yield of Cardiac Biomarker Testing in Predicting Cardiac Disease and Multisystem Inflammatory Syndrome in Children in the Pandemic Era.

OBJECTIVES: This study aimed to assess whether elevations in cardiac biomarkers are associated with pediatric cardiac diagnoses in the era of COVID-19 and multisystem inflammatory syndrome in children (MIS-C). STUDY DESIGN: This single-center retrospective study analyzed children with a troponin drawn in the emergency department or inpatient unit between April 21 and December 31, 2020. The primary outcome was the presence of a cardiac diagnosis or MIS-C. Relationships among demographics, complaint, cardiac diagnostics, and cardiac biomarkers were analyzed. RESULTS: Four hundred eighty-six patients (mean ± SD; age 13.1 ± 7.8 years; 46.7% women) met inclusion criteria, for whom a cardiac diagnosis (excluding MIS-C) was made in 27 (5.6%) patients, with MIS-C diagnosed in 14 (2.9%) patients. The sensitivity and specificity of an elevated initial high-sensitivity troponin T (hsTropT) value (>14 ng/L) in predicting the composite outcome of a cardiac diagnosis or MIS-C were 54% and 89%, respectively. Four percent of patients with negative initial troponin values were found to have a cardiac diagnosis or MIS-C. Multivariable regression analysis demonstrated that elevated hsTropT (>14 ng/L; odds ratio [OR] [95% confidence interval]: 4.9 [1.70-14.0]) and elevated N-terminal pro B-type natriuretic peptide values (>500 pg/mL; 6.4 [2.01-20.1]) were associated with increased odds of a cardiac diagnosis or MIS-C. CONCLUSIONS: Children with elevated cardiac biomarkers have increased odds of a cardiac diagnosis or MIS-C and warrant workup regardless of indication for testing. Although a negative hsTropT may reassure providers, further investigation is critical in developing algorithms to reliably exclude cardiac disease.

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.

Targeting and Modulation of the Natriuretic Peptide System in Covid-19: A Single or Double-Edged Effect?

Natriuretic peptide system (NPS) is a group of peptide hormones or paracrine factors, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and natriuretic peptide precursor C (NPC), that are structurally related. The physiological effects of NPS include natriuresis, increased glomerular filtration rate, inhibition release of renin, vasopressin, and aldosterone, sympathetic inhibition, vasodilatations, and prevents cardiac hypertrophy and remodeling. ANP has immunological effects, as it is produced locally from immune cells; it regulates innate and adaptive immune responses. Metabolism and degradation of ANP are achieved by neutral endopeptidase (NEP), also known as neprilysin. Coronavirus disease 2019 (Covid-19) pandemic may lead to acute lung injury (ALI) and/or respiratory distress syndrome (ARDS). The underlying causes of inflammatory and immunological disorders in patients with severe Covid-19 are connected to the immune over-stimulation with the subsequent release of pro-inflammatory cytokines. Covid-19 severity is linked with high ANP serum levels regardless of acute cardiac injury. Inflammatory stimuli appear to be linked with the release of NPs, which anti-inflammatory effects prevent the development of ALI/ARDS in Covid-19. Therefore, neprilysin inhibitors like sacubitril increase endogenous NPs and may reduce the risk of ALI in Covid-19 due to the potentiation of endogenous anti-inflammatory effects of NPs. However, sacubitril increases gastrin-releasing peptide, cathepsin G and release of pro-inflammatory cytokines that are inactivated by neprilysin. In conclusion, NPs and neprilysin have cardio-pulmonary protective effects against Covid-19-induced ALI/ARDS. Neprilysin inhibitor sacubitril has dual protective and harmful effects regarding metabolizing vasoactive peptides by neprilysin. These findings require potential reevaluation of the effect of neprilysin inhibitors in managing Covid-19.

The prognostic value of biomarker levels and chest imaging in patients with COVID-19 presenting to the emergency department.

INTRODUCTION: We aimed to compare the prognostic value of a quantitative CT severity score with several laboratory parameters, particularly C-reactive protein, Procalcitonin, Neutrophil to lymphocyte ratio, D-dimer, ferritin, lactate dehydrogenase, lactate, troponin and B-type Natriuretic Peptide in predicting in-hospital mortality. METHODS: This was a retrospective chart review study of COVID-19 patients who presented to the Emergency Department of a tertiary care center between February and December 2020. All patients ≥18 years old who tested positive for the COVID-19 real-time reverse transcriptase polymerase chain reaction and underwent CT imaging at presentation were included. The primary outcome was the prognostic ability of CT severity score versus biomarkers in predicting in-hospital mortality. RESULTS: The AUCs were: D-dimer (AUC: 0.67 95% CI = 0.57-0.77), CT severity score (0.66, 95% CI = 0.55-0.77), LDH (0.66, 95% CI = 0.55-0.77), Pro-BNP (0.65, 95% CI = 0.55-0.76), NLR (0.64, 95% CI = 0.53-0.75) and troponin (0.64, 95% CI = 0.52-0.75). In the stepwise logistic regression, age (OR = 1.07 95% CI = 1.05-1.09), obesity (OR = 2.02 95% CI = 1.25-3.26), neutrophil/lymphocyte ratio (OR = 1.02 95% CI = 1.01-1.04), CRP (OR = 1.01 95% CI = 1.004-1.01), lactate dehydrogenase (OR = 1.003 95% CI = 1.001-1.004) and CT severity score (OR = 1.17 95% CI = 1.12-1.23) were significantly associated with in-hospital mortality. CONCLUSION: In summary, CT severity score outperformed several biomarkers as a prognostic tool for covid related mortality. In COVID-19 patients requiring lung imaging, such as patients requiring ICU admission, patients with abnormal vital signs and those requiring mechanical ventilation, the results suggest obtaining and calculating the CT severity score to use it as a prognostic tool. If a CT was not performed, the results suggest using LDH, CRP or NLR if already done as prognostic tools in COVID-19 as these biomarkers were also found to be prognostic in COVID-19 patients.

Serial cardiac biomarkers for risk stratification of patients with COVID-19.

OBJECTIVES: Several studies have demonstrated an association between elevated cardiac biomarkers and adverse outcomes in patients with COVID-19. However, the prognostic and predictive capability of a multimarker panel in a prospectively collected, diverse "all-comers" COVID-19 population has not been fully elucidated. DESIGN & METHODS: We prospectively assessed high sensitivity cardiac troponin I (hsTnI), NT-pro B-type Natriuretic Peptide (NT-proBNP), Galectin-3 (Gal-3), and procalcitonin (PCT) in 4,282 serial samples from 358 patients admitted with symptomatic, RT-PCR confirmed SARS-CoV-2 infection. Outcomes examined were 30-day in-hospital mortality and requirement for intubation within 10 days. RESULTS: Baseline hsTnI had the highest AUC for predicting 30-day mortality (0.81; 95% CI, 0.73-0.88), followed by NT-proBNP (0.80; 0.74-0.86), PCT (0.77; 0.70-0.84), and Gal-3 (0.68; 0.60-0.76). HsTnI < 3.5 ng/L at baseline identified patients at low risk for in-hospital mortality (NPV 95.9%, sensitivity 97.3%) and 10-day intubation (NPV 90.4%, sensitivity 88.5%). Continuous, log-2 increases in troponin concentration were associated with reduced survival (p < 0.001) on Kaplan-Meier curves and increased risk of 30-day mortality: HR 1.26 (1.16-1.37) in univariate and 1.19 (1.03-1.4) in multivariate models. Time-varying doubling of concentrations of hsTnI and Gal-3 were associated with increased risk of 30-day mortality (adjusted HR 1.21, 1.06-1.4, and 1.92, 1.40-2.6). CONCLUSION: HsTnI, NT-proBNP, Gal-3, and PCT are elevated at baseline in patients that have worse outcomes from COVID-19. HsTnI was the only independent predictor of 30-day mortality and intubation. Time-varying, doubling in hsTnI and Gal-3 further aided in prognostication of adverse outcomes. These results support the use of hsTnI for triaging patients with COVID-19.

Right ventricular dysfunction in patients with COVID-19 pneumonitis whose lungs are mechanically ventilated: a multicentre prospective cohort study.

Cardiovascular complications due to COVID-19, such as right ventricular dysfunction, are common. The combination of acute respiratory distress syndrome, invasive mechanical ventilation, thromboembolic disease and direct myocardial injury creates conditions where right ventricular dysfunction is likely to occur. We undertook a prospective, multicentre cohort study in 10 Scottish intensive care units of patients with COVID-19 pneumonitis whose lungs were mechanically ventilated. Right ventricular dysfunction was defined as the presence of severe right ventricular dilation and interventricular septal flattening. To explore the role of myocardial injury, high-sensitivity troponin and N-terminal pro B-type natriuretic peptide plasma levels were measured in all patients. We recruited 121 patients and 118 (98%) underwent imaging. It was possible to determine the primary outcome in 112 (91%). Severe right ventricular dilation was present in 31 (28%), with interventricular septal flattening present in nine (8%). Right ventricular dysfunction (the combination of these two parameters) was present in seven (6%, 95%CI 3-13%). Thirty-day mortality was 86% in those with right ventricular dysfunction as compared with 45% in those without (p = 0.051). Patients with right ventricular dysfunction were more likely to have: pulmonary thromboembolism (p < 0.001); higher plateau airway pressure (p = 0.048); lower dynamic compliance (p = 0.031); higher plasma N-terminal pro B-type natriuretic peptide levels (p = 0.006); and raised plasma troponin levels (p = 0.048). Our results demonstrate a prevalence of right ventricular dysfunction of 6%, which was associated with increased mortality (86%). Associations were also observed between right ventricular dysfunction and aetiological domains of: acute respiratory distress syndrome; ventilation; thromboembolic disease; and direct myocardial injury, implying a complex multifactorial pathophysiology.

[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.