Educational Recommendations on Selected Analytical and Clinical Aspects of Natriuretic Peptides with a Focus on Heart Failure: A Report from the IFCC Committee on Clinical Applications of Cardiac Bio-Markers

Abstract The IFCC Committee on Clinical Applications of Cardiac Bio-Markers (C-CB) has directives and initiatives focused on providing evidence-based educational resources to aid and improve understanding around key analytical and clinical aspects of cardiac biomarkers used in clinical practice and the research setting. As a task force, we have previously published position statements and recommendations focused on use and analytical aspects of high-sensitivity cardiac troponin assays. The current educational document is the first from the C-CB highlighting important biochemical, analytical, and clinical aspects as they relate to the natriuretic peptides (NPs), including B-type natriuretic peptide (BNP) and N-terminal pro–B-type natriuretic peptide (NT-proBNP), with a focus on heart failure.

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Heart Failure and Diabetes Mellitus: Biomarkers in Risk Stratification and Prognostication

Applied Sciences ◽

10.3390/app11104397 ◽

2021 ◽

Vol 11 (10) ◽

pp. 4397

Author(s):

Michael Lichtenauer ◽

Peter Jirak ◽

Vera Paar ◽

Brigitte Sipos ◽

Kristen Kopp ◽

...

Keyword(s):

Diabetes Mellitus ◽

Heart Failure ◽

Ejection Fraction ◽

Risk Stratification ◽

Natriuretic Peptides ◽

Predictive Ability ◽

High Sensitivity ◽

Routine Practice ◽

Reduced Ejection Fraction ◽

Novel Biomarkers

Heart failure (HF) and type 2 diabetes mellitus (T2DM) have a synergistic effect on cardiovascular (CV) morbidity and mortality in patients with established CV disease (CVD). The aim of this review is to summarize the knowledge regarding the discriminative abilities of conventional and novel biomarkers in T2DM patients with established HF or at higher risk of developing HF. While conventional biomarkers, such as natriuretic peptides and high-sensitivity troponins demonstrate high predictive ability in HF with reduced ejection fraction (HFrEF), this is not the case for HF with preserved ejection fraction (HFpEF). HFpEF is a heterogeneous disease with a high variability of CVD and conventional risk factors including T2DM, hypertension, renal disease, older age, and female sex; therefore, the extrapolation of predictive abilities of traditional biomarkers on this population is constrained. New biomarker-based approaches are disputed to be sufficient for improving risk stratification and the prediction of poor clinical outcomes in patients with HFpEF. Novel biomarkers of biomechanical stress, fibrosis, inflammation, oxidative stress, and collagen turn-over have shown potential benefits in determining prognosis in T2DM patients with HF regardless of natriuretic peptides, but their role in point-to-care and in routine practice requires elucidation in large clinical trials.

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Natriuretic Peptides and Analytical Barriers

Clinical Chemistry ◽

10.1373/clinchem.2016.254714 ◽

2017 ◽

Vol 63 (1) ◽

pp. 50-58 ◽

Cited By ~ 22

Author(s):

Vlad C Vasile ◽

Allan S Jaffe

Keyword(s):

Heart Failure ◽

Clinical Practice ◽

Natriuretic Peptide ◽

Natriuretic Peptides ◽

Myocardial Function ◽

Specific Assay ◽

Peptide System ◽

Cardiovascular Homeostasis ◽

Natriuretic Peptide System

Abstract BACKGROUND The natriuretic peptide system is an endocrine, autocrine and paracrine system that plays an important role in the maintenance of cardiovascular homeostasis. Biomarkers based on these peptides are important diagnostic and prognostic tools for myocardial function. CONTENT Although natriuretic peptides were discovered more than 2 decades ago, their intricate and complex biology is associated with important questions not yet elucidated. The diversity of circulating forms of natriuretic peptides, the distinct expression of these forms in particular patients, and the heterogeneity of heart failure forms, along with specific assay-related and preanalytic issues, cause assays to be poorly harmonized. SUMMARY This review presents the relevant issues related to the biology of natriuretic peptides and differences between assays with immediate implications for clinical practice.

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New biohumoral markers of differential diagnosis in patients with suspected heart failure

Medicinski pregled ◽

10.2298/mpns1006387m ◽

2010 ◽

Vol 63 (5-6) ◽

pp. 387-392

Author(s):

Radomir Matunovic ◽

Zdravko Mijailovic ◽

Milorad Rabrenovic ◽

Violeta Rabrenovic

Keyword(s):

Heart Failure ◽

Congestive Heart Failure ◽

Natriuretic Peptide ◽

Correct Diagnosis ◽

Clinical Manifestations ◽

High Sensitivity ◽

Renal Diseases ◽

Significant Implication ◽

Acute Patient ◽

Degree Of Certainty

Introduction. In the regular clinic practice, the assessment of the cause of dispnea is a dilemma which has a significant implication in both the estimation of prognosis and treatment of the patient. In emergency cases, when most necessary, it is often very difficult to determine whether dispnea was caused by a heart or lung disease. Role of natriuretic peptide in patients with dispnea. An acute patient with dispnea might suffer serious consequences of inadequately established diagnosis so congestive heart failure (CHF) has to be diagnosed quickly and precisely in the ER. Unfortunately, symptoms and signs of CHF are unspecific, it is sometimes impossible to obtain an adequate anamnesis and diagnosic procedures currently applied are either insufficiently precise or provide scarce information or can not always be performed under appropriate conditions. On the basis of previous findings, it has been proved that brain natriuretic peptide (BNP) can considerably contribute to the establishment of correct diagnosis as well as to the possibility of introducing an adequate therapy for those patients. However, the real value of those peptides should be estimated in relation to other clinical manifestations and indicators and the specifics of examined patients including the age, gender and the presence or absence of pulmonary or renal diseases. Natriuretic peptide in accessement gradient of heart failure. Determination of natriuretic peptide has represented most probably the greatest progress in diagnosing the heart failure since the introduction of echocardiography into practice. Its high sensitivity and negative predicted value makes it a valid test for excluding congestive heart failure with a very high degree of certainty.

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Short- and Long-term Biologic Variability of Galectin-3 and Other Cardiac Biomarkers in Patients with Stable Heart Failure and Healthy Adults

Clinical Chemistry ◽

10.1373/clinchem.2015.246553 ◽

2016 ◽

Vol 62 (2) ◽

pp. 360-366 ◽

Cited By ~ 24

Author(s):

Emily I Schindler ◽

Jeffrey J Szymanski ◽

Karl G Hock ◽

Edward M Geltman ◽

Mitchell G Scott

Keyword(s):

Heart Failure ◽

Troponin I ◽

Prognostic Biomarker ◽

High Sensitivity ◽

Cardiac Biomarkers ◽

Healthy Individuals ◽

Short Term ◽

Galectin 3 ◽

Short And Long Term

Abstract BACKGROUND Galectin-3 (Gal-3) has been suggested as a prognostic biomarker in heart failure (HF) patients that may better reflect disease progression than traditional markers, including B-type natriuretic peptide (BNP) and cardiac troponins. To fully establish the utility of any biomarker in HF, its biologic variability must be characterized. METHODS To assess biologic variability, 59 patients were prospectively recruited, including 23 male and 16 female patients with stable HF and 10 male and 10 female healthy individuals. Gal-3, BNP, and high-sensitivity cardiac troponin I (hs-cTnI) were assayed at 5 time points within a 3-week period to assess short-term biologic variability. Long-term (3-month) biologic variability was assessed with samples collected at enrollment and after 4, 8, and 12 weeks. RESULTS Among healthy individuals, mean short-term biologic variability, expressed as intraindividual CV (CVI), was 4.5% for Gal-3, 29.0% for BNP, and 14.5% for hs-cTnI; long-term biologic variability was 5.5% for Gal-3, 34.7% for BNP, and 14.7% for hs-cTnI. In stable HF patients, mean short-term biologic variability was 7.1% for Gal-3, 22.5% for BNP, and 8.5% for hs-cTnI, and mean long-term biologic variability was 7.7% for Gal-3, 27.6% for BNP, and 9.6% for hs-cTnI. CONCLUSIONS The finding that Gal-3 has minimal intraindividual biological variability adds to its potential as a useful biomarker in HF patients.

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Abstract 2793: Comparison of Midregional Pro-atrial Natriuretic Peptide, B-type Natriuretic Peptide, and Amino-terminal Pro-B-type Natriuretic Peptide in Patients with Chronic Heart Failure: Influencing Factors, Detection of Left Ventricular Systolic Dysfunction, and Prediction of Death

Circulation ◽

10.1161/circ.116.suppl_16.ii_620-b ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Deddo Moertl ◽

Martin Huelsmann ◽

Joachim Struck ◽

Andreas Gleiss ◽

Alexandra Hammer ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Atrial Natriuretic Peptide ◽

Natriuretic Peptide ◽

Influencing Factors ◽

Natriuretic Peptides ◽

Left Ventricular Systolic Dysfunction ◽

Systolic Dysfunction ◽

Left Ventricular ◽

Ventricular Systolic Dysfunction

Background: Although natriuretic peptides are increasingly used for the management of chronic heart failure (CHF), there are sparse comparative data. Therefore, we compared the importance of influencing factors, the ability to detect left ventricular systolic dysfunction, and the prognostic power of midregional pro-atrial natriuretic peptide (MR-proANP), B-type natriuretic peptide (BNP), and aminoterminal pro-B-type natriuretic peptide (NT-proBNP) in patients with chronic heart failure. Methods and Results: MR-proANP, using a new assay directed at the midregion of aminoterminal-proANP, was compared with BNP and NT-proBNP, using conventional assays, in 797 patients with CHF. All three natriuretic peptides were independently influenced by left ventricular ejection fraction (LVEF), glomerular filtration rate (GFR), and the presence of ankle edema. Area under receiver-operator characteristic curves for detection of an LVEF <40% were similar between MR-proANP (0.799 [0.753– 0.844]) and BNP (0.803 [0.757– 0.849]), and NT-proBNP (0.730 [0.681– 0.778]. During a median observation time of 68 months, 492 patients died. In multiple Cox regression analysis each natriuretic peptide was the strongest prognostic parameter among various clinical variables, but proportion of explained variation showed that NT-proANP was a significantly stronger predictor of death than NT-proBNP and BNP (Figure ). Conclusions: Despite similarities in influencing factors and detection of reduced LVEF, MR-proANP outperformed BNP and NT-proBNP in the prediction of death. A new assay technology and the high biological stability of MR-proANP are potential explanations for these findings.

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High sensitivity, contemporary and point-of-care cardiac troponin assays: educational aids developed by the IFCC Committee on Clinical Application of Cardiac Bio-Markers

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2018-1211 ◽

2019 ◽

Vol 57 (5) ◽

pp. 623-632 ◽

Cited By ~ 21

Author(s):

Paul O. Collinson ◽

Amy K. Saenger ◽

Fred S. Apple ◽

Keyword(s):

Cardiac Troponin ◽

Task Force ◽

Clinical Chemistry ◽

Point Of Care ◽

High Sensitivity ◽

Laboratory Medicine ◽

International Federation ◽

Cardiac Biomarkers ◽

Educational Materials ◽

Extensive Information

AbstractThe International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) formed a Task Force on the Application of Cardiac Bio-markers (TF-CB) in 2008, re-designated in 2018 as a committee (C-CB), to produce educational materials on cardiac biomarkers. Established in June 2017, definitive tables covering the majority of high-sensitivity, contemporary and point-of-care (POC) cTn assays have been developed by the C-CB and are available on the IFCC website. These tables provide extensive information about assays’ analytical characteristics and encompass information on diagnostic discriminants, particularly the 99th percentiles, as provided by the manufacturers.

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N-terminal Pro-brain Natriuretic Peptide plasma levels are Associated With a Short-Term Diagnosis of Cancer in Patients with Coronary Artery Disease

10.21203/rs.3.rs-135088/v1 ◽

2020 ◽

Author(s):

José Tuñón ◽

Álvaro Aceña ◽

Ana Pello ◽

Sergio Ramos-Cillán ◽

Juan Martínez-Milla ◽

...

Keyword(s):

Heart Failure ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Plasma Levels ◽

High Sensitivity ◽

Short Term ◽

Artery Disease

Abstract Background N-terminal pro-brain natriuretic peptide (NT-proBNP) plasma levels are increased in patients with cancer. In this paper we test whether NT-proBNP may identify patients who are going to receive a future cancer diagnosis (CD) in the short term. Methods We studied 962 patients with stable coronary artery disease and free of cancer and heart failure at baseline. NT-proBNP, galectin-3, monocyte chemoattractant protein-1, high-sensitivity C-reactive protein, high-sensitivity cardiac troponin I (hsTnI), and calcidiol (vitamin D) plasma levels were assessed. The primary outcome was new CD. Results After 5.40 (2.81-6.94) years of follow-up, 59 patients received a CD. NT-proBNP [HR 1.036 CI (1.015-1.056) per increase in 100 pg/ml; p=0.001], previous atrial fibrillation [HR 3.140 CI (1.196-8.243); p=0.020], and absence of previous heart failure [HR 0.067 CI (0.006-0.802); p=0.033] were independent predictors of a receiving a CD in first three years of follow-up. None of the variables analyzed predicted a CD beyond this time. A previous history of heart failure was present in 3.3% of patients receiving a CD in the first three years of follow-up, in 0.0% of those receiving this diagnosis beyond three years, and in 12.3% of patients not developing cancer (p=0.036). Conclusions In patients with coronary artery disease, NT-proBNP is an independent predictor of CD in the first three years of follow-up but not later, suggesting that it could be detecting subclinical undiagnosed cancers. The existence of previous heart failure does not account for these differences. New studies in large populations are needed to confirm these findings.

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Extrém magas B típusú natriureticus prohormon prognosztikai szerepe a szívelégtelenség miatt kezelt betegek kórházi halálozására

Orvosi Hetilap ◽

10.1556/650.2017.30761 ◽

2017 ◽

Vol 158 (20) ◽

pp. 779-782

Author(s):

Béla Bózsik ◽

Erzsébet Nagy ◽

Miklós Somlói ◽

János Tomcsányi

Keyword(s):

Heart Failure ◽

Hospital Mortality ◽

Hospital Stay ◽

Natriuretic Peptide ◽

Natriuretic Peptides ◽

Prognostic Value ◽

Response To Therapy ◽

Cardiology Department ◽

The Difference ◽

One Year

Abstract: Introduction: Patients hospitalized for heart failure have a very high in-hospital as well as one-year mortality. Natriuretic peptides play both a diagnostic and a prognostic role in this disease. Changes of natriuretic peptide levels in response to therapy are a well-known prognostic marker. Regarding in-hospital mortality, however, little is known about the prognostic value of extremely high levels of natriuretic peptides measured on admission. Aim: To decide whether extremely high levels of B-type natriuretic peptide have a prognostic value with regard to in-hospital mortality. Method: NT-proBNP levels on admission and in-hospital mortality were extracted retrospectively from the data of patients treated with heart failure in the cardiology department of the Hospital of St. John of God in Budapest. We separately analyzed the data of patients hospitalized for heart failure in 2015 with extremely high initial NT-proBNP levels. The cut-off value in this regard was 10 000 ng/l. We also analyzed the comorbidities of these patients. Results: The median NT-proBNP level of those patients who survived beyond the index hospital stay in the last 10 years was 4842 ng/l, whereas the median NT-proBNP level of those 182 patients who died during their hospital stay was 10 688 ng/l (p<0.001). In the year 2015, we treated 118 patients with an NT-proBNP level above 10 000 ng/l. Thirteen of these patients died, which means that their in-hospital mortality exceeded 10%. In comparison, the in-hospital mortality of all heart failure patients was 5.8%. The difference of median NT-proBNP levels of surviving versus deceased patients in this group with extremely high NT-proBNP levels was no longer significant (17 080 ng/l vs. 19 152 ng/l). Conclusions: Patients with an NT-proBNP level of >10 000 ng/l on admission have a significantly higher in-hospital mortality. The difference of NT-proBNP levels of surviving versus deceased patients in the group with admission NT-proBNP levels >10 000 ng/l is no longer significant. We could not identify any etiological factors that would explain these extremely high NT-proBNP levels or the excess in-hospital mortality. Orv Hetil. 2017; 158(20): 779–782.

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Redefining Cardiac Biomarkers in Predicting Mortality of Inpatients With COVID-19

Hypertension ◽

10.1161/hypertensionaha.120.15528 ◽

2020 ◽

Vol 76 (4) ◽

pp. 1104-1112 ◽

Cited By ~ 7

Author(s):

Juan-Juan Qin ◽

Xu Cheng ◽

Feng Zhou ◽

Fang Lei ◽

Gauri Akolkar ◽

...

Keyword(s):

Natriuretic Peptide ◽

Troponin I ◽

Cox Model ◽

Cardiac Injury ◽

High Sensitivity ◽

Cardiac Biomarkers ◽

Cardiac Biomarker ◽

Increased Risk ◽

Poor Outcomes ◽

Prognostic Power

The prognostic power of circulating cardiac biomarkers, their utility, and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multicentered retrospective study, we enrolled 3219 patients with diagnosed COVID-19 admitted to 9 hospitals from December 31, 2019 to March 4, 2020, to estimate the associations and prognostic power of circulating cardiac injury markers with the poor outcomes of COVID-19. In the mixed-effects Cox model, after adjusting for age, sex, and comorbidities, the adjusted hazard ratio of 28-day mortality for hs-cTnI (high-sensitivity cardiac troponin I) was 7.12 ([95% CI, 4.60–11.03] P <0.001), (NT-pro)BNP (N-terminal pro-B-type natriuretic peptide or brain natriuretic peptide) was 5.11 ([95% CI, 3.50–7.47] P <0.001), CK (creatine phosphokinase)-MB was 4.86 ([95% CI, 3.33–7.09] P <0.001), MYO (myoglobin) was 4.50 ([95% CI, 3.18–6.36] P <0.001), and CK was 3.56 ([95% CI, 2.53–5.02] P <0.001). The cutoffs of those cardiac biomarkers for effective prognosis of 28-day mortality of COVID-19 were found to be much lower than for regular heart disease at about 19%–50% of the currently recommended thresholds. Patients with elevated cardiac injury markers above the newly established cutoffs were associated with significantly increased risk of COVID-19 death. In conclusion, cardiac biomarker elevations are significantly associated with 28-day death in patients with COVID-19. The prognostic cutoff values of these biomarkers might be much lower than the current reference standards. These findings can assist in better management of COVID-19 patients to improve outcomes. Importantly, the newly established cutoff levels of COVID-19–associated cardiac biomarkers may serve as useful criteria for the future prospective studies and clinical trials.

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Clinical Applications of Natriuretic Peptides in Heart Failure and Atrial Fibrillation

International Journal of Molecular Sciences ◽

10.3390/ijms20112824 ◽

2019 ◽

Vol 20 (11) ◽

pp. 2824 ◽

Cited By ~ 6

Author(s):

Masako Baba ◽

Kentaro Yoshida ◽

Masaki Ieda

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Natriuretic Peptides ◽

Clinical Applications ◽

Current Evidence ◽

Clinical Prognosis ◽

Diagnosis And Management ◽

Artery Disease

Natriuretic peptides (NPs) have become important diagnostic and prognostic biomarkers in cardiovascular diseases, particularly in heart failure (HF). Diagnosis and management of coronary artery disease and atrial fibrillation (AF) can also be guided by NP levels. When interpreting NP levels, however, the caveat is that age, sex, body mass index, renal dysfunction, and race affect the clearance of NPs, resulting in different cut-off values in clinical practice. In AF, NP levels have been associated with incident AF in the general population, recurrences after catheter ablation, prediction of clinical prognosis, and the risk of stroke. In this article, we first review and summarize the current evidence and the roles of B-type NP and atrial NP in HF and coronary artery disease and then focus on the increasing utility of NPs in the diagnosis and management of and the research into AF.

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