The multidimensional value of natriuretic peptides in heart failure, integrating laboratory and clinical aspects.

Natriuretic peptides (NP) play an essential role in heart failure (HF) regulation, and their measurement has improved diagnostic and prognostic accuracy. Clinical symptoms and objective measurements, such as NP levels, should be included in the HF definition to render it more reliable and consistent among observers, hospitals, and healthcare systems. BNP and NT-proBNP are reasonable surrogates for cardiac disease, and their measurement is critical to early diagnosis and risk stratification of HF patients. NPs should be measured in all patients presenting with dyspnea or other symptoms suggestive of HF to facilitate early diagnosis and risk stratification. Both BNP and NT-proBNP are currently used for guided HF management and display comparable diagnostic and prognostic accuracy. Standardized cutoffs for each NP assay are essential for data comparison. The value of NP testing is recognized at various levels, including patient empowerment and education, analytical and operational issues, clinical HF management, and cost-effectiveness.

Improvement in Echocardiographic and Diagnostic Biomarkers after Systemic Glucocorticoid Therapy in Infants with Pulmonary Hypertension.

OBJECTIVE: To assess the effect of treating pulmonary hypertension (PH) in infants younger than 1 year of age with systemic glucocorticoids while using echocardiographic and diagnostic biomarkers as measures of efficacy. STUDY DESIGN: A retrospective chart review was performed on 17 hospitalized infants younger than 1 year of age at St Louis Children's Hospital who received a 5- to 7-day course of systemic glucocorticoid treatment followed by a 3-week taper with no significant intracardiac shunts from January 1, 2017, to December 31, 2021. Quantitative echocardiographic indices for PH, N-terminal pro b-type natriuretic peptide, and/or b-type natriuretic peptide levels were collected before glucocorticoid treatment, after the glucocorticoid burst, and after the 21-day taper. RESULTS: Mean (±SD) gestational age was 32.1 (±5.8) weeks, 5 infants were (29%) concomitantly treated with sildenafil, and 8 were male. Twelve were classified as World Health Organization group 3 PH (71%) and 5 as World Health Organization group 1 PH. There were significant improvements 30 days after glucocorticoid initiation in b-type natriuretic peptide levels (P = .008), PCO2 (P = .03), eccentricity index (P = .005), right ventricular ejection time (P = .04), pulmonary artery acceleration time (P = .002), and pulmonary artery acceleration time-to-right ventricular ejection time ratio (P = .02). Tricuspid regurgitation velocity was not able to be assessed. There were no mortalities during the study timeline. CONCLUSIONS: In our retrospective study, systemic glucocorticoid therapy was well tolerated and appeared to be associated with significant improvement in cardiopulmonary function in infants with PH. Further prospective study in a larger sample is warranted.

N-terminal pro-B-type natriuretic peptide levels vary by ethnicity and are associated with insulin sensitivity after gestational diabetes mellitus.

BACKGROUND: Individuals of South Asian origin have a greater risk of cardiovascular disease after gestational diabetes mellitus (GDM) than European individuals. B-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-proBNP) are commonly used for heart failure screening and diagnosis, but biologically BNP exerts several beneficial cardiovascular effects primarily by counteracting the renin-angiotensin-aldosterone-system. We asked whether ethnic differences in circulating NT-proBNP levels could be explained by the differences in cardiometabolic and inflammatory risk markers? METHODS: We examined 162 South Asian and 107 Nordic women in Norway 1-3 years after GDM with a clinical examination, fasting blood samples and an oral glucose tolerance test. We measured the levels of NT-proBNP, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), leptin, adiponectin and markers of insulin sensitivity, such as the Matsuda insulin sensitivity index (ISI). Finally, we tried to identify which independent covariate best mediated the ethnic differences in NT-proBNP. RESULTS: The mean (SD) age was 35.3 (4.5) years, BMI 29.1 (6.0) kg/m2, waist-height ratio 0.60 (0.08) and 164 women (61%) had prediabetes/diabetes. Notably, South Asian women had lower levels of NT-proBNP than Nordic women in both the normoglycemic and prediabetes/diabetes groups (median (IQR) 26  (15-38)  vs. 42 (22-66) ng/L, p < 0.001). Higher NT-proBNP levels were associated with greater insulin sensitivity in both South Asian and Nordic women (p = 0.005 and p < 0.001). South Asian women had higher levels of hsCRP (median (IQR) 2.2 (1.1-4.4) vs. 1.2 (0.3-4.2) mg/L), IL-6 (2.3 (1.5-3.2) vs. 1.5 (1.5-2.5) pg/mL), leptin (1647 (1176-2480) vs. 1223 (876-2313) pmol/L), and lower adiponectin levels (7.2 (5.3-9.3) vs. 10.0 (7.2-13.5) mg/L) and Matsuda ISI (2.4 (1.7-3.7) vs. 4.2 (2.9-6.1), pall<0.01) than Nordic women. Even after adjusting for these differences, higher NT-proBNP levels remained associated with insulin sensitivity (22% higher NT-proBNP per SD Matsuda ISI, p = 0.015). Insulin sensitivity and adiponectin mediated 53% and 41% of the ethnic difference in NT-proBNP. CONCLUSIONS: NT-proBNP levels are lower in South Asian than in Nordic women after GDM. Lower NT-proBNP levels correlate with impaired insulin sensitivity. Lower NT-proBNP levels in South Asian women could, therefore, be attributed to impaired insulin sensitivity rather than total body fat.

Sex differences in the diagnostic algorithm of screening for heart failure by symptoms and NT-proBNP in patients with type 2 diabetes.

OBJECTIVES: This study aimed to assess the guideline recommended diagnostic tools NT-proBNP and NYHA classification, with a focus on sex-specific differences. BACKGROUND: Patients with Type 2 Diabetes (T2D) face a heart failure (HF) risk up to four times higher than those without T2D, particularly affecting women more than twice as much as men. Despite distinct pathophysiological differences between men and women, there are currently no sex-specific recommendations for the diagnostic algorithm of HF in diabetic patients. METHODS: A total of 2083 patients with T2D were enrolled, and the primary endpoint was heart failure during hospitalization within a 5-year timeframe. The secondary endpoint was all-cause death. RESULTS: In female patients, frequency of HF diagnosis prior to or during hospitalization and mortality did not differ significantly between NYHA II and III, in contrast to male patients. Additionally, there was no notable difference in mean NT-proBNP levels between NYHA stage II and III only in female patients. The multivariable regression analysis highlighted NYHA classification not to be a predictor of NT-proBNP levels in female but solely in male patients. On multivariable Cox regression NYHA score was also no significant risk factor for occurence of HF in female patients. Furthermore, there was no significant disparity in mortality between men with NT-proBNP levels between 125 and 400 pg/ml and those below 125 pg/ml, whereas in women mortality was significantly higher in the group with NT-proBNP levels between 125 and 400 pg/ml than below 125 pg/ml. CONCLUSION: These findings suggest that NYHA classification may not be the most suitable tool for assessing the diagnosis of HF in female patients with T2D. Moreover, the need for consideration of a more symptom-independent screening for HF in female patients with T2D and re-evaluation of current guidelines especially regarding sex-specific aspects is highlighted.

Detecting heart stress using NT-proBNP in patients with type 2 diabetes mellitus and hypertension or high-normal blood pressure: a cross-sectional multicentric study.

BACKGROUND: We evaluated the prevalence of "heart stress" (HS) based on NT-proBNP cut-points proposed by the 2023 Consensus of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in asymptomatic patients with T2DM and hypertension or high-normal blood pressure (BP) eligible for SGLT2 inhibitors (SGLT2i) and/or GLP-1 receptor agonists (GLP1-RA), drugs with proven benefits on reducing the incidence of HF, hospitalizations, cardiovascular events and mortality. METHODS: A cross-sectional multicentric study was conducted on 192 consecutive outpatients, aged ≥ 55 years, with hypertension or high-normal BP, referred to three diabetology units. NT-proBNP was collected before starting new anti-diabetic therapy. Patients with known HF were excluded, and participants were classified based on the age-adjusted NT-proBNP cut-points. RESULTS: Mean age: 70.3 ± 7.8 years (67.5% males). Patients with obesity (BMI ≥ 30 Kg/m2): 63.8%. Median NT-proBNP: 96.0 (38.8-213.0) pg/mL. Prevalence of chronic kidney disease (CKD, eGFR < 60 mL/min/1.73m2): 32.1%. Mean arterial BP: 138.5/77.0 ± 15.8/9.9 mmHg. The NT-proBNP values, according to the proposed age-adjusted cut-points, classified 28.6% of patients as "HS likely" (organize elective echocardiography and specialist evaluation), 43.2% as "HS not likely" (a grey area, repeat NT-proBNP at six months) and 28.2% as "very unlikely HS" (repeat NT-proBNP at one year). The presence of CKD and the number of anti-hypertensive drugs, but not glycemic parameters, were independently associated with HS. CONCLUSIONS: According to NT-proBNP, over a quarter of T2DM patients with hypertension/high-normal BP, among those eligible for SGLT2i and/or GLP1-RA, were already at risk of cardiac damage, even subclinical. Most would receive an indication to echocardiogram and be referred to a specialist, allowing the early implementation of effective strategies to prevent or delay the progression to advanced stages of cardiac disease and overt HF.

Dynamic LVEF Decline and Serum NT-proBNP and Uric Acid Levels before Heart Transplantation are Independent Predictors of Adverse Outcomes in Young Adult Patients with Dilated Cardiomyopathy.

Background: The present study investigated the predictors of adverse outcomes in young adult patients with dilated cardiomyopathy (DCM) who underwent heart transplantation (HTx). Methods: Twenty-four young adult patients (aged 18-45 years) with DCM who underwent HTx in our hospital from January 2012 to December 2022 were included in this retrospective analysis. Pre- and post-HTx data were collected for echocardiography, N-terminal pro-brain natriuretic peptide (NT-proBNP), and uric acid (UA). Data collected at the time of DCM diagnosis were designated as baseline data. Post-HTx assessments were conducted at 1 week and 3, 6, 12, and 36 months post-HTx. The primary endpoint was defined as any adverse event, including left ventricular ejection fraction (LVEF) < 50% (n = 3), 50% increase in right or left ventricular diameter (n = 12), or death (n = 2). Patients were categorized into a non-adverse-event group (n = 12) or an adverse-event group (n = 12). Results: Baseline NT-proBNP (p = 0.014) and UA (p = 0.012) were significantly higher in the adverse-event group than in the non-adverse-event group. Baseline NT-proBNP > 7390 pg/mL (relative risk (RR) = 7.412, p = 0.046), UA > 542 µmol/L (RR = 8.838, 95% confidence interval (95% CI) = 1.541-50.694, p = 0.014), and sustained reduction in LVEF ( ≥ 3%) over a 2-year pharmacological treatment prior to HTx (RR = 3.252, p = 0.046) were significantly associated with an increased risk of adverse events post-HTx. Conclusions: In young adult DCM patients post-HTx, heightened baseline levels of NT-proBNP and UA levels and a sustained reduction in LVEF over time prior to undergoing an HTx are significantly associated with an increased risk of adverse events post-HTx. Future studies are needed to observe whether individualized monitoring strategies could reduce the incidence of adverse events following HTx in these patients.

Intra-amniotic infection and/or inflammation is associated with fetal cardiac concentric hypertrophy and diastolic dysfunction in preterm labor and preterm prelabor rupture of membranes.

BACKGROUND: Preterm delivery is associated with cardiovascular remodeling and dysfunction in children and adults. However, it is unknown whether these effects are caused by the neonatal consequences of preterm birth or if these are already present in utero. OBJECTIVE: We evaluated fetal cardiac morphology and function in fetuses of mothers admitted for preterm labor or preterm prelabor rupture of membranes and the association of these changes with the presence of intra-amniotic infection and/or inflammation. STUDY DESIGN: In this prospective cohort study, fetal echocardiography and amniocentesis were performed at admission in singleton pregnant women with preterm labor and/or preterm prelabor rupture of membranes between 24.0 and 34.0 weeks' gestation with (intra-amniotic infection and/or inflammation group, n=41) and without intra-amniotic infection and/or inflammation (non-intra-amniotic infection and/or inflammation, n=54). Controls (n=48) were outpatient pregnant women without preterm labor or preterm prelabor rupture of membranes. Intra-amniotic infection was defined by a positive amniotic fluid culture or positive 16S ribosomal RNA gene. Intra-amniotic inflammation was defined by using the amniotic fluid interleukin-6 cutoff levels previously reported by our group being >1.43 ng/mL in preterm prelabor rupture of membranes and >13.4 ng/mL in preterm labor. Fetal cardiac morphology and function was evaluated using echocardiography, and troponin-I and N-terminal pro-brain natriuretic peptide concentrations were measured in amniotic fluid from women with preterm labor or preterm prelabor rupture of membranes and compared with 20 amniotic fluid Biobank samples obtained for reasons other than preterm labor or preterm prelabor rupture of membranes or cardiac pathology. The data were adjusted for the estimated fetal weight below the 10th percentile and for preterm prelabor rupture of membranes at admission and also for gestational age at amniocentesis when amniotic fluid biomarkers were compared. RESULTS: From 2018 to 2021, 143 fetuses were included; 95 fetuses were from mothers admitted with a diagnosis of preterm labor or preterm prelabor rupture of membranes, and among those, 41 (28.7%) were in the intra-amniotic infection and/or inflammation group and 54 (37.8%) were in the non-intra-amniotic infection and/or inflammation group. A total of 48 (33.6%) fetuses were included in the control group. Fetuses with preterm labor and/or preterm prelabor rupture of membranes had signs of subclinical cardiac concentric hypertrophy (median left wall thickness of 0.93 [interquartile range, 0.72-1.16] in the intra-amniotic infection and/or inflammation group; 0.79 [0.66-0.92] in the non-intra-amniotic infection and/or inflammation group; and 0.69 [0.56-0.83] in controls; P<.001) and diastolic dysfunction (tricuspid A duration 0.23 seconds [0.21-0.25], 0.24 [0.22-0.25], and 0.21 [0.2-0.23]; P=.007). Systolic function was similar among groups. Higher values of amniotic fluid troponin I (1413 pg/mL [927-2334], 1190 [829-1636], and 841 [671-959]; P<.001) and N-terminal pro-brain natriuretic peptide were detected (35.0%, 17%, and 0%; P=.005) in fetuses with preterm labor or preterm prelabor rupture of membranes when compared with the control group. The highest N-terminal pro-brain natriuretic peptide concentrations were found in the intra-amniotic infection and/or inflammation group. CONCLUSION: Fetuses with preterm labor or preterm prelabor rupture of membranes showed signs of cardiac remodeling and subclinical dysfunction, which were more pronounced in those exposed to intra-amniotic infection and/or inflammation. These findings support that the cardiovascular effects observed in children and adults born preterm have, at least in part, a prenatal origin.

Prediction of new-onset heart failure in patients with type 2 diabetes derived from ALTITUDE and CANVAS.

AIM: To create and validate a prediction model to identify patients with type 2 diabetes (T2D) at high risk of new-onset heart failure (HF), including those treated with a sodium-glucose cotransporter-2 (SGLT2) inhibitor. METHODS: A prediction model was developed from the Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints (ALTITUDE), a trial in T2D patients with albuminuria or cardiovascular disease. We included 5081 patients with baseline N-terminal pro B-type natriuretic peptide (NT-proBNP) measurement and no history of HF. The model was developed using Cox regression and validated externally in the placebo arm of the Canagliflozin Cardiovascular Assessment Study (CANVAS), which included 996 participants with T2D and established cardiovascular disease or high cardiovascular risk, and in patients treated with canagliflozin. RESULTS: ALTITUDE participants (mean age 64 ± 9.8 years) had a median serum NT-proBNP level of 157 (25th-75th percentile 70-359) pg/mL. Higher NT-proBNP level, troponin T (TnT) level and body mass index (BMI) emerged as significant and independent predictors of new-onset HF in both cohorts. The model further contained urinary albumin-to-creatinine ratio, glycated haemoglobin, age, haematocrit, and use of calcium channel blockers. A prediction model including these variables had a C-statistic of 0.828 (95% confidence interval [CI] 0.801-0.855) in ALTITUDE and 0.800 (95% CI 0.720-0.880) in CANVAS. The C-statistic of this model increased to 0.847 (95% CI 0.792-0.902) in patients after 1 year of canagliflozin treatment. CONCLUSION: In patients with T2D, higher NT-proBNP level, TnT level and BMI are independent and externally validated predictors of new-onset HF, including patients using an SGLT2 inhibitor. This newly developed model may identify patients at high risk of new-onset HF, contributing to early recognition and possibly prevention.

Baseline NT-proBNP levels as a predictor of short-and long-term prognosis in COVID-19 patients: a prospective observational study.

BACKGROUND: Up to 20% of COVID-19 patients can suffer COVID-19-related myocardial injury. Elevated cardiac biomarkers, such as hs-cTnT and NT-proBNP, have been related to worse short-term prognosis. However, data on NT-proBNP and long-term prognosis are scarce. We have evaluated the potential association of baseline age-adjusted NT-proBNP levels and outcomes at one-year follow-up in COVID-19 patients. METHODS: This was a single-center prospective study of 499 COVID-19 patients in whom NT-proBNP was assessed at hospital admission. NT-proBNP levels were age-adjusted and patients were classified as high or low NT-proBNP. Clinical and demographic characteristics, comorbidities, laboratory results, and in-hospital complications and mortality were compared between the two groups. Survivors of the acute phase of COVID-19 were followed up for one year from admission to detect readmissions and mortality. RESULTS: The 68 patients with high NT-proBNP levels at hospital admission were older, with more cardiovascular risk factors, cardiovascular disease, comorbidities, myocardial injury, and higher levels of inflammatory markers than patients with low NT-proBNP levels. They also had more in-hospital complications and a higher acute-phase mortality rate (60.3% vs. 10.2%, p < 0.001). High NT-proBNP levels were an independent marker of death during hospitalization (HR 1.95; CI 1.07-3.52). At one-year follow-up, high NT-proBNP levels were independently associated with mortality (HR 2.69; CI 1.47-4.89). Among survivors of the acute phase of COVID-19, there were no differences in hospital readmissions between those with high vs. low NT-proBNP levels, but survivors with high baseline NT-proBNP levels showed a higher 1-year mortality rate (7.4% vs. 1.3%, p = 0.018). CONCLUSIONS: High age-adjusted NT-proBNP levels at the time of hospital admission for COVID-19 are associated with poor short and long-term prognosis. High NT-proBNP seems also to be related to worse prognosis in survivors of the acute phase of COVID-19. A closer follow-up on these patients may be crucial.

Clinical characteristics and influencing factors of severe fever with thrombocytopenia syndrome complicated by viral myocarditis: a retrospective study.

OBJECTIVE: This study aimed to investigate the clinical characteristics of severe fever with thrombocytopenia syndrome complicated by viral myocarditis (SFTS-VM) and analyze relevant influencing factors. METHODS: Retrospective analysis was conducted on clinical data from 79 SFTS-VM patients, categorized into common (SFTS-CVM, n = 40) and severe groups (SFTS-SVM, n = 39). Clinical manifestations, laboratory results, cardiac ultrasonography, and electrocardiogram features were analyzed. Univariate and multivariate analyses identified significant indicators, which were further assessed using ROC curves to predict SFTS-SVM. RESULTS: SFTS-SVM group exhibited higher rates of hypotension, shock, abdominal pain, cough with sputum, and consciousness disorders compared to SFTS-CVM group. Laboratory findings showed elevated platelet count, ALT, AST, amylase, lipase, LDH, D-dimer, procalcitonin, TNI, and NT-proBNP in SFTS-SVM. Abnormal electrocardiograms, especially atrial fibrillation, were more prevalent in SFTS-SVM (P < 0.05). Multivariate analysis identified elevated LDH upon admission (OR = 1.004, 95% CI: 1-1.008, P = 0.050), elevated NT-proBNP (OR = 1.005, 95% CI: 1.001-1.008, P = 0.007), and consciousness disorders (OR = 112.852, 95% CI: 3.676 ~ 3464.292, P = 0.007) as independent risk factors for SFTS-SVM. LDH and NT-proBNP had AUCs of 0.728 and 0.744, respectively, in predicting SFTS-SVM. Critical values of LDH (> 978.5U/L) and NT-proBNP (> 857.5pg/ml)) indicated increased likelihood of SFTS progression into SVM. CONCLUSION: Elevated LDH, NT-proBNP, and consciousness disorders independently correlate with SFTS-SVM. LDH and NT-proBNP can aid in early identification of SFTS-SVM development when above specified thresholds.

Reference intervals for high sensitivity cardiac troponin I and N-terminal pro-B-type natriuretic peptide in children and adolescents on the Siemens Atellica.

OBJECTIVES: The cardiac biomarkers high sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are utilised in paediatric healthcare for the diagnosis and prognostic assessment of many conditions including myocarditis, congenital heart disease, multisystem inflammatory syndrome in children (MIS-C) and heart failure. However, the standardised age-related reference intervals, 99th percentile cut-offs and clinical guidelines are not available, making the interpretation of these biomarkers challenging. This study aimed to generate normative data in a paediatric cohort for the Siemens Atellica® IM 1300 analyser. METHODS: Residual plasma samples were collected from children aged up to 17 years attending primary care and out-patient settings and with no apparent evidence of cardiac dysfunction, renal dysfunction or other confounders. Reference intervals were generated using the 2.5th-97.5th percentiles, and 99th percentile cut-offs determined according to CLSI EP28-A3c. RESULTS: Statistical analysis revealed that partitioning was not required for gender for either biomarker. The reference interval for hs-cTnI for children aged one month to 16 years (n=292, 146 females and 146 males) was <14 ng/L with a 99th percentile cut-off of 19 ng/L. The reference interval for NT-proBNP for children aged one month up to one year was <714 ng/L (n=14) and for children aged 1-16 years (n=339) was <295 ng/L. CONCLUSIONS: This is the first paediatric reference interval data generated on the Siemens Atellica® solution. These reference intervals and 99th percentiles will inform clinical decisions in the paediatric cardiology setting.

Pathological findings associated with the updated European Society of Cardiology 2022 guidelines for preoperative cardiac testing: an observational cohort modelling study.

BACKGROUND: In 2022, the European Society of Cardiology updated guidelines for preoperative evaluation. The aims of this study were to quantify: (1) the impact of the updated recommendations on the yield of pathological findings compared with the previous guidelines published in 2014; (2) the impact of preoperative B-type natriuretic peptide (NT-proBNP) use for risk estimation on the yield of pathological findings; and (3) the association between 2022 guideline adherence and outcomes. METHODS: This was a secondary analysis of MET-REPAIR, an international, prospective observational cohort study (NCT03016936). Primary endpoints were reduced ejection fraction (EF<40%), stress-induced ischaemia, and major adverse cardiovascular events (MACE). The explanatory variables were class of recommendations for transthoracic echocardiography (TTE), stress imaging, and guideline adherence. We conducted second-order Monte Carlo simulations and multivariable regression. RESULTS: In total, 15,529 patients (39% female, median age 72 [inter-quartile range: 67-78] yr) were included. The 2022 update changed the recommendation for preoperative TTE in 39.7% patients, and for preoperative stress imaging in 12.9% patients. The update resulted in missing 1 EF <40% every 3 fewer conducted TTE, and in 4 additional stress imaging per 1 additionally detected ischaemia events. For cardiac stress testing, four more investigations were performed for every 1 additionally detected ischaemia episodes. Use of NT-proBNP did not improve the yield of pathological findings. Multivariable regression analysis failed to find an association between adherence to the updated guidelines and MACE. CONCLUSIONS: The 2022 update for preoperative cardiac testing resulted in a relevant increase in tests receiving a stronger recommendation. The updated recommendations for TTE did not improve the yield of pathological cardiac testing.

Analytical and clinical performance evaluation of a new NT-proBNP assay.

BACKGROUND: The study evaluated the performance of the Mindray N-terminal pro-B-type natriuretic peptide (NT-proBNP) in a healthy population in China, focusing on creating a reference range for future clinical applications adjusted according to different demographics. METHODS: The study measured NT-proBNP in 2277 healthy individuals. We analyzed age and sex-stratified data, performed precision, accuracy, linearitcvy, and detection limit studies, and evaluated method comparison and consistency between Roche and Mindray assays on 724 serum samples. We used Excel 2010, Medcalc, and GraphPad Prism 9. RESULTS: In males, the 97.5th centile NT-proBNP concentration at age < 45, 45 to 54, 55 to 64, 65 to 74 and ≧ 75 were 89.4 ng/L, 126 ng/L, 206 ng/L, 386 ng/L and 522 ng/L, respectively. In females, the concentration of NT-proBNP at the same age was 132 ng/L, 229 ng/L, 262 ng/L, 297 ng/L and 807 ng/L, respectively. The repeatability precision coefficient of variation (CV%) for NT-proBNP was between 0.86 and 1.65 in analytical performance. In contrast, the reproducibility precision (CV%) for NT-proBNP was between 1.52 and 3.22, respectively. The study found a bias of accuracy of 3.73% in low-value samples (concentration: 148.69) and 7.31% in high-value samples (concentration: 1939.08). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 125 ng/L were 96.6%, 92.3%, 84.2%, and 98.5%, respectively. In contrast, those of 300 ng/L were 94.0%, 98.2%, 95.7% and 97.5%, respectively. CONCLUSIONS: The Mindray NT-proBNP assay showed increased levels in both males and females with age, with higher levels in women. It performs well and aligns with manufacturer specifications. We recommend adjusting cutoff values based on demographic factors.

Early changes in cardiac troponin T and NT-proBNP levels in neonates receiving ECMO support: a single-center experience.

OBJECTIVE: This study aimed to examine the changes in absolute value and decline rate of early serum cardiac troponin T (cTnT) and N-terminal pro b-type natriuretic peptide (NT-proBNP) in neonates who received veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) support therapy within the first week of life. METHODS: We retrospectively collected clinical data and laboratory test results of 18 neonates who underwent V-A ECMO support within one week of birth, from July 2021 to June 2023, using the electronic medical record system. These patients were categorized into survival and death groups. Comparative analyses of the absolute values and decline rates of cTnT and NT-proBNP were made between the groups at baseline, and at 24, 48, and 72 h post-ECMO initiation. RESULTS: Out of the 18 neonates, 12 survived (survival rate: 66.7%), while 6 succumbed. The survival group exhibited significantly lower absolute values of cTnT and NT-proBNP than the death group, and their decline rates were significantly higher. Notably, all neonates without an early decline in cTnT and NT-proBNP levels were in the death group. CONCLUSION: The early changes in the absolute value and decline rate of serum cTnT and NT-proBNP in neonates undergoing V-A ECMO may serve as predictors of their prognosis.

Liver fibrosis, NT-ProBNP and mortality in patients with MASLD: A population-based cohort study.

BACKGROUND & AIM: Liver fibrosis is the strongest predictor of liver-related mortality in many chronic liver diseases. NT-ProBNP is independently associated with cardiovascular mortality in general population settings. Here, we evaluate the relative contribution of non-invasively identified liver fibrosis and NT-ProBNP on all-cause and cardiovascular mortality in patients with metabolic (dysfunction)-associated steatotic liver disease (MASLD). METHODS AND RESULTS: Serum NT-ProBNP levels were measured in 4229 patients with MASLD from the general population without a known history of heart failure that participated in the 1999-2004 cycles of the National Health and Nutrition Examination Survey. Presence of liver fibrosis was estimated using the Fibrosis-4 index (FIB-4). We applied Cox proportional hazard models adjusted for cardiovascular risk factors to evaluate the association between NT-ProBNP and FIB-4 levels and all-cause and cardiovascular mortality through December 2019. Mortality was lower for participants with normal levels of both biomarkers, intermediate if a single biomarker was elevated and highest when both were above the chosen threshold. In the multivariable-adjusted models, both elevated FIB-4 (≥2.67) and elevated NT-ProBNP levels (≥125 pg/ml) were independently associated with higher risks of all-cause mortality (HR 2.2, 95 % CI 1.5-3.2 and HR 1.6, 95 % CI 1.4-2.0, respectively) and cardiovascular mortality (HR 2.1, 95 % CI 1.2-3.7 and HR 2.1, 95 % CI 1.5-2.9, respectively). The associations remained consistent in subgroup analyses based on sex, obesity and age. CONCLUSIONS: Both FIB-4 and NT-ProBNP are independently associated with higher mortality in patients with MASLD. Their combined use might prove useful to risk-stratify patients in clinical practice.

Artificial intelligence universal biomarker prediction tool.

Through experiencing cardiopulmonary arrest, an artificial intelligence universal biomarker prediction tool was developed to help patients understand improvement in the trends of their disease. PyPI tool handles two biomarkers, hbA1c for diabetes and NP-proBNP for heart failure, to predict the next hospital visit. Predicting improvement in disease is a great hope for patients.

Electrocardiographic abnormalities and NT-proBNP levels at long-term follow-up of patients with dyspnea after pulmonary embolism.

OBJECTIVES: Electrocardiogram (ECG) and measurement of plasma brain natriuretic peptides (BNP) are established markers of right ventricular dysfunction (RVD) in the setting of acute pulmonary embolism (PE) but their value at long-term follow-up is largely unknown. The purpose of this prospective study was to determine the prevalence of ECG abnormalities, describe levels of N-terminal proBNP (NT-proBNP), and establish their association with dyspnea at long-term follow-up after PE. DESIGN: All Swedish patients diagnosed with acute PE in 2005 (n = 5793) were identified through the Swedish National Patient Registry. Surviving patients in 2007 (n = 3510) were invited to participate. Of these, 2105 subjects responded to a questionnaire about dyspnea and comorbidities. Subjects with dyspnea or risk factors for development of chronic thromboembolic pulmonary hypertension were included in the study in a secondary step, which involved collection of blood samples and ECG registration. RESULTS: Altogether 49.3% had a completely normal ECG. The remaining participants had a variety of abnormalities, 7.2% had atrial fibrillation/flutter (AF). ECG with any sign of RVD was found in 7.2% of subjects. Right bundle branch block was the most common RVD sign with a prevalence of 6.4%. An abnormal ECG was associated with dyspnea. AF was associated with dyspnea, whereas ECG signs of RVD were not. 61.2% of subjects had NT-proBNP levels above clinical cut-off (>125 ng/L). The degree of dyspnea did not associate independently with NT-proBNP levels. CONCLUSIONS: We conclude that the value of ECG and NT-proBNP in long term follow-up after PE lies mostly in differential diagnostics.

Prognostic utility of serum NT-proBNP (fragments 1-76aa and 13-71aa) and galectin-3 in predicting death and re-hospitalisation due to cardiovascular events in patients with heart failure.

Patients with heart failure (HF) are at a higher risk of rehospitalisation. In this study, we investigated the prognostic utility of galectin-3 (Gal-3) and NT-proBNP fragments (1-76aa and 13-71aa) as biomarkers to predict outcomes for patients with HF. We collected blood samples from patients with HF (n = 101). Gal-3 and NT-proBNP fragments (1-76aa and 13-71aa) concentrations were measured by immunoassay. Survival analysis and Cox proportional regression models were used to determine the prognostic utility of Gal-3 and NT-proBNP fragments. In patients with increased baseline levels of NT-proBNP1-76 the time to primary endpoint (cardiovascular death or re-hospitalisation) was significantly shorter (p = 0.0058), but not in patient with increased baseline levels of Gal-3 or NTproBNP13-71. Patients with increased levels of NT-proBNP13-71aa at 1 month showed reduced time to the primary endpoint (p = 0.0123). Our findings demonstrated that Gal-3 and NT-proBNP can be used as prognostic biomarkers to stratify patients with HF.

NT-pro BNP level at dialysis initiation is a useful biomarker for predicting hospitalization for ischemic heart disease.

BACKGROUND: Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular disease including stroke, heart failure, and ischemic heart disease (IHD). To prevent the occurrence and progression of CVD, a reliable prognostic cardiac biomarker is essential. We investigated the prognostic value of NT-proBNP for each incident type of CVD. METHODS: Male patients from the Ibaraki Dialysis Initiation Cohort (iDIC) study with preserved serum samples from dialysis initiation day (n = 212) were analyzed. Patients were classified into four groups according to quartiles of baseline NT-pro BNP levels. The relationship between NT-proBNP levels at the initiation of dialysis and the subsequent incidence of hospitalization events due to IHD, heart failure, and stroke was analyzed. RESULTS: The incidence rate for hospitalization due to IHD was significantly higher in the highest NT-proBNP category (Log rank p = 0.008); those of stroke and heart failure showed no significant differences among quartiles. Cox proportional hazards regression analysis revealed that serum NT-proBNT was the only prognostic factor for hospitalization for IHD after adjustment by major known IHD risk factors. (HR, 1.008; 95% confidence interval, 1.002-1.014; p = 0.01) The ROC curve analysis for the incidence of hospitalization due to IHD showed that NT-proBNP had an area under the curve (AUC) of 0.759 (95% CI 0.622-0.897; p = 0.004) at a cut-off value of 956.6 pg/mL. CONCLUSION: NT-proBNP measurement at the initiation of dialysis therapy is useful to predict later hospitalization for IHD. TRIAL REGISTRATION: UMIN000010806.

Influence of a 7-day Transalpine Trail Run on cardiac biomarkers and myocardial function.

Intense physical exercise is known to increase cardiac biomarkers; however, it is unclear, whether this phenomenon is physiological, or if it indicates myocardial tissue injury. The aim of our study was to investigate the effects of seven consecutive days of excessive endurance exercise on continuous assessment of cardiac biomarkers, function, and tissue injury. During a 7-day trail-running competition (Transalpine Run, distance 267.4 km, altitude ascent/descent 15556/14450 m), daily blood samples were obtained for cardiac biomarkers (hs-TnT, NT-proBNP, and suppression of tumorigenicity-2 protein (ST2)) at baseline, after each stage and 24-48 h post-race. In addition, echocardiography was performed every second day, cardiac magnetic resonance imaging (CMR) before (n = 7) and after (n = 16) the race. Twelve (eight males) out of 17 healthy athletes finished all seven stages (average total finish time: 43 ± 8 h). Only NT-proBNP increased significantly (3.6-fold, p = 0.009) during the first stage and continued to increase during the race. Hs-TnT revealed an incremental trend during the first day (2.7-fold increase, p = 0.098) and remained within the pathological range throughout the race. ST2 levels did not change during the race. All cardiac biomarkers completely returned to physiological levels post-race. NT-proBNP kinetics correlated significantly with mild transient reductions in right ventricular function (assessed by TAPSE, tricuspid annular plane systolic function; r = -0.716; p = 0.014). No significant echocardiographic changes in LV dimensions, LV function, or relevant alterations in CMR were observed post-race. In summary, this study shows that prolonged, repetitive, high-volume exercise induced a transient, significant increase in NT-proBNP associated with right ventricular dysfunction without corresponding left ventricular functional or structural impairment.