Hemodynamic-Guided Heart Failure Management in Patients With Either Prior HF Hospitalization or Elevated Natriuretic Peptides.

BACKGROUND: In patients with symptomatic heart failure (HF) and previous heart failure hospitalization (HFH), hemodynamic-guided HF management using a wireless pulmonary artery pressure (PAP) sensor reduces HFH, but it is unclear whether these benefits extend to patients who have not been recently hospitalized but remain at risk because of elevated natriuretic peptides (NPs). OBJECTIVES: This study assessed the efficacy and safety of hemodynamic-guided HF management in patients with elevated NPs but no recent HFH. METHODS: In the GUIDE-HF (Hemodynamic-Guided Management of Heart Failure) trial, 1,000 patients with New York Heart Association (NYHA) functional class II to IV HF and either previous HFH or elevated NP levels were randomly assigned to hemodynamic-guided HF management or usual care. The authors evaluated the primary study composite of all-cause mortality and total HF events at 12 months according to treatment assignment and enrollment stratum (HFH vs elevated NPs) by using Cox proportional hazards models. RESULTS: Of 999 evaluable patients, 557 were enrolled on the basis of a previous HFH and 442 on the basis of elevated NPs alone. Those patients enrolled by NP criteria were older and more commonly White persons with lower body mass index, lower NYHA class, less diabetes, more atrial fibrillation, and lower baseline PAP. Event rates were lower among those patients in the NP group for both the full follow-up (40.9 per 100 patient-years vs 82.0 per 100 patient-years) and the pre-COVID-19 analysis (43.6 per 100 patient-years vs 88.0 per 100 patient-years). The effects of hemodynamic monitoring were consistent across enrollment strata for the primary endpoint over the full study duration (interaction P = 0.71) and the pre-COVID-19 analysis (interaction P = 0.58). CONCLUSIONS: Consistent effects of hemodynamic-guided HF management across enrollment strata in GUIDE-HF support consideration of hemodynamic monitoring in the expanded group of patients with chronic HF and elevated NPs without recent HFH. (Hemodynamic-Guided Management of Heart Failure [GUIDE-HF]; NCT03387813).

Retrospective cohort study on the increase of bnP and troponin-t in pediatric patients positive to covid-19.

Background: According to data from the World Health Organization updated to September 30, 2022, SARS-CoV-2 is a viral disease, that infected six hundred million people and claimed six and a half million victims in all over the world. Some authors describe the alteration of blood parameters in pediatric age following COVID-19 such as: anomalies of the leukocyte formula, CK-MB and LDH enzymes, C reactive protein (PCR) and procalcitonin (PCT). Based on these studies we wanted to focus on two cardiac biomarkers: type B natriuretic peptide (BNP) and high sensitivity cardiac troponin (cTnT-hs). In order to suggest a strategy aimed at preventing the possible occurrence of cardiovascular complications in children we monitored them in patients with specific anti-SARS-CoV-2 immunoglobulins (IgG). Method(s): From November 2020 to December 2021, 53 children with positive IgG to SARS-CoV-2 by immunochromatographic method were tested for BNP and cTnT-hs. Samples collected in potassium EDTA tubes were tested for BNP by a fluorescence immunoassay. cTnT-hs was determined with an electrochemiluminescence sandwich test, which employs two specific monoclonal antibodies directed against cardiac troponin. The BNP cutoff is 100 pg/mL for patients aged 1 to 14 years, while that of cTnT-hs is 14 ng/L. All patients were monitored from hospitalization to discharge. Result(s): At least one of the two biomarkers resulted pathologic in 35 (66%) patients, while 18 (34%) were negative. The 35 pathologic cases were distributed as follows: 12 were simultaneously positive for cTnT-hs and BNP;13 were only positive for BNP, and 10 only positive for cTnT-hs. Sick children had a BNP mean value of 634 pg/mL at hospitalization, and of 94 pg/mL at discharge. For cTnT-hs, the initial mean value was 46 ng/l and the final was 17 ng/L. Twelve children with both altered values were monitored for a longer time, as they returned negative more slowly. Repeated dosages of the two analytes from hospitalization to discharge, showed a constant decrease over the time. After about ten days from the first dosage, both parameters returned to values near to the relative cutoffs. Conclusion(s): Measuring BNP and cTnt-hs can be useful for screening and monitoring pediatric patients positive for anti-SARSCoV-2 IgG.Copyright © 2022 EDIZIONI MINERVA MEDICA.

Statistics and Management COVID-19 in Kosovo-Case Study Hospital of Ferizaj

Infectious diseases are disorders caused by microorganisms such as bacteria, viruses, parasites or fungi. According to the World Health Organization, infectious diseases cause about 26% of the world's deaths and are the leading cause of death in people younger than 50 years old. Infectious diseases are classified into new infectious diseases, which include SARS-1, SARS-2, bird flu, etc., and recurrent diseases, which include pre-existing infections with known incidence and geographical spread. Coronaviruses are a family of viruses widely found in animals and humans, responsible for a variety of diseases, ranging from common cold to much more severe diseases which often lead to pneumonia. The group of new diseases also includes Coronavirus 2019 (COVID-19), which initially causes a respiratory infection with the continuation of other complications. This virus is a new type of beta-coronavirus, which first appeared in China and later spread very fast all over the world leading to a global pandemic. Disease monitoring should primarily include erythrocyte sedimentation rate, leukocyte count, leukocyte formula, C-reactive protein (CRP), determination of Troponin I (hsTnI) and T (cTnT), pro-B Type N-terminal natriuretic peptide (NT-proBNP), fibrinogen and D-dimer levels. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Statistical Processing of Relationship Between Biomarkers and Disease Severity Caused by COVID-19 Infection-Delta Variant

Severe infectious disease caused by acute respiratory syndrome, COVID-19 (SARS-CoV-2), spread rapidly worldwide, infecting several million people. According to scientific data, the disease develops through several different stages. After 2–4 days of infection and disease development, the lower respiratory tract is attacked and in a relatively short time interstitial pneumonia develops in a certain number of patients (with genetic predisposition between 5 and 10% of cases). Patients infected with COVID-19 have symptoms such as very high temperatures, fever, persistent cough, joint and bone pain, in some cases diarrhea, and loss of appetite and taste. Disease monitoring should primarily include erythrocyte sedimentation rate, leukocyte count, leukocyte count formula, C-reactive protein (CRP), determination of troponin I (hsTnI) and T (cTnT) levels, N-terminal pro-B natriuretic peptide (NT-proBNP), fibrinogen, and D-dimer level. Previous studies have shown that in pneumonia developed from chronic and acute obstructive pulmonary infections, high levels of D-dimer are observed in patients, and it is suggested that this parameter can be used as a specific prognostic biomarker, and the values higher than > 1000 ng/ml represent increased risk factors for mortality in patients with COVID-19. Because vascular thrombosis affects the promotion of an unfavorable clinical progression for the patient, the identification of early and accurate predictors of the worst outcome seems to be essential for timely and appropriate anticoagulant treatment in patients with SARS-CoV-2 infection. Overall, these data suggest that acute myocardial damage, or heart failure, may be an important indicator of disease severity and adverse prognosis in patients with COVID-19. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

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.

Cardiac biomarkers in COVID-19: a narrative review

The diagnosis and risk stratification of coronavirus disease 2019 (COVID-19) is primarily based on discretionary use of laboratory resources. Several lines of evidence now attest that cardiovascular disease not only is a frequent complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but its pre-existence may increase the risk of morbidity, disability, and death in patients with COVID-19. To this end, routine assessment of biomarkers of cardiac injury (i.e., cardiac troponin I or T) and dysfunction (e.g., natriuretic peptides) has emerged as an almost essential practice in patients with moderate, severe, and critical COVID-19 illness. Therefore, this narrative review aims to provide an overview of cardiac involvement in patients with SARS-CoV-2 infection as well as the clinical background for including cardiac biomarkers within specific panels of laboratory tests for managing COVID-19 patients. © 2021 International Federation of Clinical Chemistry and Laboratory Medicine. All rights reserved.

A Novel Paradigm Based on ST2 and Its Contribution towards a Multimarker Approach in the Diagnosis and Prognosis of Heart Failure: A Prospective Study during the Pandemic Storm.

BACKGROUND: Acute heart failure (HF) represents an increasingly common and challenging presentation in the emergency room, also inducing a great socio-economic burden. Extensive research was conducted toward finding an ideal biomarker of acute HF, both in terms of sensitivity and specificity, but today practicians' interest has shifted towards a more realistic multimarker approach. Natriuretic peptides (NPs) currently represent the gold standard for diagnosing HF in routine clinical practice, but novel molecules, such as sST2, emerge as potentially useful biomarkers, providing additional diagnostic and prognostic value. METHODS: We conducted a prospective, single-center study that included 120 patients with acute HF and 53 controls with chronic HF. Of these, 13 patients (eight with acute HF, five from the control group) associated the coronavirus-19 disease (COVID-19). The diagnosis of HF was confirmed by a complete clinical, biological and echocardiographic approach. RESULTS: The serum levels of all studied biomarkers (sST2, NT-proBNP, cardiac troponin) were significantly higher in the group with acute HF. By area under the curve (AUC) analysis, we noticed that NT-proBNP (AUC: 0.976) still had the best diagnostic performance, closely followed by sST2 (AUC: 0.889). However, sST2 was a significantly better predictor of fatal events, showing positive correlations for both in-hospital and at 1-month mortality rates. Moreover, sST2 was also associated with other markers of poor prognosis, such as the use of inotropes or high lactate levels, but not with left ventricle ejection fraction, age, body mass index or mean arterial pressure. sST2 levels were higher in patients with a positive history of COVID-19 as compared with non-COVID-19 patients, but the differences were statistically significant only within the control group. Bivariate regression showed a positive and linear relationship between NT-proBNP and sST2 (r(120) = 0.20, p < 0.002). CONCLUSIONS: we consider that sST2 has certain qualities worth integrating in a future multimarker test kit alongside traditional biomarkers, as it provides similar diagnostic value as NT-proBNP, but is emerging as a more valuable prognostic factor, with a better predictive value of fatal events in patients with acute HF.

A Contemporary View of Natriuretic Peptides in the SARS-CoV-2 Era.

The heart releases natriuretic peptides (NPs) which represent an important hormonal axis with cardiorenal protective effects. In view of their properties, NPs have pathophysiologic, diagnostic and prognostic implications in several cardiovascular diseases (CVDs). Severe pulmonary inflammation, as induced by the SARS-COV2, may increase pulmonary pressure with potential influence on NPs release, whereby normal cardiovascular integrity becomes impaired. Moreover, pre-existing CVDs are strong negative prognostic factors since they exacerbate the effects of the viral infection and lead to worse outcomes. In this context, it may be expected that NPs exert a key protective role toward the virus infection whereas an impairment of NPs release contributes to the virus deleterious effects. In this review article we explore the potential involvement of NPs in the COVID-19 disease. To this aim, we will first focus on the interactions between NPs and the Ang II/ATIR arm of the renin-angiotensin-aldosterone system (RAAS) as well as with the protective ACE2/Ang (1-7) arm of the RAAS. Subsequently, we will review evidence that strongly supports the role of increased NT-proBNP level as a marker of cardiac damage and of worse prognosis in the COVID-19 affected patients. Finally, we will discuss the potential therapeutic benefits of these protective hormones toward the viral infection through their endothelial protective function, anti-inflammatory and anti-thrombotic effects. In conclusion, the potential implications of NPs in the SARS-CoV-2 infection, as discussed in our article, represent an important issue that deserves to be fully investigated.

[Myocardial injury in coronavirus disease 19 (Covid-19): main pathophysiological mechanisms and clinical utility of cardiac biomarkers]. / Atteintes myocardiques au cours de la maladie à coronavirus 19 (Covid-19) : principaux mécanismes physiopathologiques et utilité clinique des biomarqueurs cardiaques.

Covid-19 is responsible for myocardial injury in many infected patients, which is associated with severe disease and critical illness. The mechanisms by which SARS-CoV-2 may cause myocardial damage involve direct effect of the virus in cardiac cells and indirect effect due to the clinical consequences of Covid-19. Cardiomyocytes are well known to express Angiotensin-Converting Enzyme-2 receptors (ACE-2) to facilitate the virus cell entry, which could explain the occurrence of myocarditis, functional alterations in the myocardium, and more rarely, myocardial infarction. Myocardial injury may also be secondary to systemic inflammation or coagulopathy due to complicated Covid-19. The existence of a cardio-intestinal axis with alteration of tryptophan metabolism in the small bowel leading first to colitis and then to systemic inflammation has also been evoked to explain the myocardial injury. Morphological and metabolic disturbances of the heart during the Covid-19 are associated with elevated concentrations of cardiac blood biomarkers, mainly troponins and natriuretic peptides. The determination of these biomarkers has proven to be very useful for diagnosis, prognosis, and risk stratification. Indeed, recent data demonstrated that about 20% of infected patients admitted to the hospital have elevated troponin or BNP levels, and Covid-19 patients with elevated troponin concentrations beyond the diagnostic threshold (99th percentile) were associated with a higher risk of in-hospital mortality. In conclusion, after more than a year of a unique global pandemic, it is now clearly established that myocardial injury during Covid-19 is frequent and strongly contributes to the severity of the disease. Cardiac alterations secondary to direct infection of cardiac cells by SARS-CoV-2 or to the clinical consequences of Covid-19 are associated with elevated levels of cardiac biomarkers in blood, whose measurement is crucial in clinical decision making.

Cardiovascular biomarkers in patients with COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has increased awareness that severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) may have profound effects on the cardiovascular system. COVID-19 often affects patients with pre-existing cardiac disease, and may trigger acute respiratory distress syndrome (ARDS), venous thromboembolism (VTE), acute myocardial infarction (AMI), and acute heart failure (AHF). However, as COVID-19 is primarily a respiratory infectious disease, there remain substantial uncertainty and controversy whether and how cardiovascular biomarkers should be used in patients with suspected COVID-19. To help clinicians understand the possible value as well as the most appropriate interpretation of cardiovascular biomarkers in COVID-19, it is important to highlight that recent findings regarding the prognostic role of cardiovascular biomarkers in patients hospitalized with COVID-19 are similar to those obtained in studies for pneumonia and ARDS in general. Cardiovascular biomarkers reflecting pathophysiological processes involved in COVID-19/pneumonia and its complications have a role evaluating disease severity, cardiac involvement, and risk of death in COVID-19 as well as in pneumonias caused by other pathogens. First, cardiomyocyte injury, as quantified by cardiac troponin concentrations, and haemodynamic cardiac stress, as quantified by natriuretic peptide concentrations, may occur in COVID-19 as in other pneumonias. The level of those biomarkers correlates with disease severity and mortality. Interpretation of cardiac troponin and natriuretic peptide concentrations as quantitative variables may aid in risk stratification in COVID-19/pneumonia and also will ensure that these biomarkers maintain high diagnostic accuracy for AMI and AHF. Second, activated coagulation as quantified by D-dimers seems more prominent in COVID-19 as in other pneumonias. Due to the central role of endothelitis and VTE in COVID-19, serial measurements of D-dimers may help physicians in the selection of patients for VTE imaging and the intensification of the level of anticoagulation from prophylactic to slightly higher or even therapeutic doses.

Characterization of NT-proBNP in a large cohort of COVID-19 patients.

AIMS: Extensive research regarding the association of troponin and prognosis in coronavirus disease 2019 (COVID-19) has been performed. However, data regarding natriuretic peptides are scarce. N-terminal pro B-type natriuretic peptide (NT-proBNP) reflects haemodynamic stress and has proven useful for risk stratification in heart failure (HF) and other conditions such as pulmonary embolism and pneumonia. We aimed to adequately characterize NT-proBNP concentrations using a large cohort of patients with COVID-19, and to investigate its association with prognosis. METHODS AND RESULTS: Consecutive patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and available NT-proBNP determinations, from March 1st to April 20th, 2020 who completed at least 1-month follow-up or died, were studied. Of 3080 screened patients, a total of 396 (mean age 71.8 ± 14.6 years, 61.1% male) fulfilled all the selection criteria and were finally included, with a median follow-up of 53 (18-62) days. Of those, 192 (48.5%) presented NT-proBNP levels above the recommended cut-off for the identification of HF. However, only 47 fulfilled the clinical criteria for the diagnosis of HF. Patients with higher NT-proBNP during admission experienced more frequent bleeding, arrhythmias and HF decompensations. NT-proBNP was associated with mortality both in the whole study population and after excluding patients with HF. A multivariable Cox model confirmed that NT-proBNP was independently associated with mortality after adjusting for all relevant confounders (hazard ratio 1.28, 95% confidence interval 1.13-1.44, per logarithmic unit). CONCLUSION: NT-proBNP is frequently elevated in COVID-19. It is strongly and independently associated with mortality after adjusting for relevant confounders, including chronic HF and acute HF. Therefore, its use may improve early prognostic stratification in this condition.