N-terminal pro-B-type Natriuretic Peptide Measurements Research Articles

Cardiac biomarkers and effects of aficamten in obstructive hypertrophic cardiomyopathy: the SEQUOIA-HCM trial.

The role of biomarker testing in the management of obstructive hypertrophic cardiomyopathy (oHCM) is not well defined. This pre-specified analysis of SEQUOIA-HCM (NCT05186818) sought to define the associations between clinical characteristics and baseline concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI), and to evaluate effect of treatment with aficamten on biomarker concentrations. Cardiac biomarkers were measured at baseline and serially throughout the study. Regression analyses determined predictors of baseline NT-proBNP and hs-cTnI concentrations, and to evaluate whether early changes in these biomarkers relate to later changes in left ventricular outflow tract gradient (LVOT-G), other echocardiographic measures, health status, and functional capacity. Baseline concentration of NT-proBNP was associated with LVOT-G and measures of diastolic function, while hs-cTnI was associated with left ventricular thickness. Within 8 weeks of treatment with aficamten, NT-proBNP was reduced by 79% (95% CI 83%-76%, P < .001) and hs-cTnI by 41% (95% CI 49%-32%, P < .001); both biomarkers reverted to baseline after washout. Reductions in NT-proBNP and hs-cTnI by 24 weeks were strongly associated with a lowering of LVOT-G, improvement in health status, and increased peak oxygen uptake. NT-proBNP reduction strongly correlated with the majority of improvements in exercise capacity. Furthermore, the change in NT-proBNP by Week 2 was associated with the 24-week change in key endpoints. NT-proBNP and hs-cTnI concentrations are associated with key variables in oHCM. Serial measurement of NT-proBNP and hs-cTnI appears to reflect clinical response to aficamten therapy.

Setting the optimal threshold of NT-proBNP and BNP for the diagnosis of heart failure in patients over 75years.

Diagnosing acute heart failure (AHF) remains particularly challenging in older patients. Natriuretic peptides are recommended as valuable diagnostic tools in this context. This study aims to establish the diagnostic thresholds of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for AHF in patients aged over 75years, both with and without co-morbidities. In this retrospective longitudinal multicentre cohort study, data were gathered from 12071 hospitalized patients aged 75years or older, presenting with acute dyspnoea and undergoing BNP or NT-proBNP measurement within 48h of admission across 10 Assistance Publique-Hôpitaux de Paris facilities between 2011 and 2022, encompassing geriatrics, cardiology, and pulmonology departments. Final diagnoses were categorized using ICD-10 criteria as either AHF or other acute respiratory conditions such as COPD exacerbation, pulmonary embolism, and pneumonia. The mean (SD) age of the population was 84.0 (80.0, 89.0) years, with 52.7% being female. Out of these, 7946 (65.8%) were diagnosed with AHF upon discharge. For NT-proBNP, the identified 'optimal' threshold for diagnosing AHF was 1748ng/L, with a positive predictive value (PPV) of 84%. Among patients aged over 85years, a threshold of 2235pg/mL for NT-proBNP was associated with an 84% PPV. In patients with atrial fibrillation (AF), a threshold of 2332pg/mL for NT-proBNP demonstrated a PPV of 90% for AHF diagnosis. Additionally, in patients with an estimated glomerular filtration rate (eGFR)<30mL/min, a threshold of 3474pg/mL for NT-proBNP yielded a 90% PPV for AHF diagnosis. In male patients, a threshold of 1800pg/mL showed an 85% PPV for AHF diagnosis, while in patients with obesity, a threshold of 1375pg/mL demonstrated an 85% PPV for AHF diagnosis. In older patients, we found significant effects of co-morbidities on natriuretic peptides results, particularly in patients over 85years old, older patients with abnormal renal function, obesity, and atrial fibrillation. Despite the consideration of those co-morbid conditions, NT-proBNP and BNP level continue to demonstrate utility in the diagnosis of AHF in older patients.

Longitudinal NT-proBNP: Associations With Echocardiographic Changes and Outcomes in Heart Failure.

The relationship of serial NT-proBNP (N-terminal pro-B-type natriuretic peptide) measurements with changes in cardiac features and outcomes in heart failure (HF) remains incompletely understood. We determined whether common clinical covariates impact these relationships. In 2 nationwide observational populations with HF, the relationship of serial NT-proBNP measurements with serial echocardiographic parameters and outcomes was analyzed, further stratified by HF with reduced versus preserved left ventricular ejection fraction, inpatient versus outpatient enrollment, age, obesity, chronic kidney disease, atrial fibrillation, and attainment of ≥50% guideline-recommended doses of renin-angiotensin system inhibitors and β-blockers. Among 1911 patients (mean±SD age, 65.1±13.4 years; 26.6% women; 62% inpatient and 38% outpatient), NT-proBNP declined overall, with more rapid declines among inpatients, those with obesity, those with atrial fibrillation, and those attaining ≥50% guideline-recommended doses. Each doubling of NT-proBNP was associated with increases in left ventricular volume (by 6.1 mL), E/e' (transmitral to mitral annular early diastolic velocity ratio) (by 1.4 points), left atrial volume (by 3.6 mL), and reduced left ventricular ejection fraction (by -2.1%). The effect sizes of these associations were lower among patients with HF with preserved ejection fraction, atrial fibrillation, or advanced age (Pinteraction<0.001). A landmark analysis identified that an SD increase in NT-proBNP over 6 months was associated with a 27% increase in the risk of the composite event of HF hospitalization or all-cause death between 6 months and 2 years (adjusted hazard ratio, 1.27 [95% CI, 1.15-1.40]; P<0.001). The relationships between NT-proBNP and structural/functional remodeling differed by age, presence of atrial fibrillation, and HF phenotypes. The association of increased NT-proBNP with increased risk of adverse outcomes was consistent in all subgroups.

N-Terminal Pro-B-Type Natriuretic Peptide and Risk for Diabetes Mellitus and Metabolic Syndrome.

Natriuretic peptide concentrations are inversely associated with risk of diabetes mellitus and may be protective from metabolic dysfunction. We studied associations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with incident diabetes, metabolic syndrome (MetS), and MetS components. 2,899 participants with baseline (2003-2007) and follow-up (2013-2016) examinations and baseline NT-proBNP measurement in the REasons for Geographic And Racial Differences in Stroke study. Logistic regression models were fitted to incident MetS, MetS components, and diabetes; covariates included demographics, risk and laboratory factors. Incident diabetes, defined as fasting glucose ≥126 mg/dL, random glucose ≥200 mg/dL, or use of insulin or hypoglycemic drugs at follow-up but not baseline. Incident MetS, in participants with ≥3 harmonized criteria at follow-up and <3 at baseline. 310 participants (2,364 at risk) developed diabetes and 361 (2,059 at risk) developed MetS over mean 9.4 years follow-up. NT-proBNP was inversely associated with odds of incident diabetes (fully-adjusted OR per-SD higher log NT-proBNP 0.80, 95% CI 0.69-0.93) and MetS in the highest vs. lowest quartile only (fully-adjusted OR 0.59, 95% CI 0.37-0.92); the linear association with incident MetS was not statistically significant. NT-proBNP was inversely associated with incident dysglycemia in all models (fully-adjusted OR per-SD log NT-proBNP 0.65, 95% CI 0.53-0.79), but not with other MetS components. Effect modification by sex, race, age, or BMI was not observed. NT-proBNP was inversely associated with odds of diabetes, MetS, and the MetS dysglycemia component. The metabolic implications of B-type natriuretic peptides appear important for glycemic homeostasis.

Improved Cardiomyopathy Risk Prediction Using Global Longitudinal Strain and N-Terminal-Pro-B-Type Natriuretic Peptide in Survivors of Childhood Cancer Exposed to Cardiotoxic Therapy.

To leverage baseline global longitudinal strain (GLS) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP) to identify childhood cancer survivors with a normal left ventricular ejection fraction (LVEF) at highest risk of future treatment-related cardiomyopathy. St Jude Lifetime Cohort participants ≥5 years from diagnosis, at increased risk for cardiomyopathy per the International Guideline Harmonization Group (IGHG), with an LVEF ≥50% on baseline echocardiography (n = 1,483) underwent measurement of GLS (n = 1,483) and NT-proBNP (n = 1,052; 71%). Multivariable Cox regression models estimated hazard ratios (HRs) and 95% CIs for postbaseline cardiomyopathy (modified Common Terminology Criteria for Adverse Events ≥grade 2) incidence in association with echocardiogram-based GLS (≥-18) and/or NT-proBNP (>age-sex-specific 97.5th percentiles). Prediction performance was assessed using AUC in models with and without GLS and NT-proBNP and compared using DeLong's test for IGHG moderate- and high-risk individuals treated with anthracyclines. Among survivors (median age, 37.6; range, 10.2-70.4 years), 162 (11.1%) developed ≥grade 2 cardiomyopathy 5.1 (0.7-10.0) years from baseline assessment. The 5-year cumulative incidence of cardiomyopathy for survivors with and without abnormal GLS was, respectively, 7.3% (95% CI, 4.7 to 9.9) versus 4.4% (95% CI, 3.0 to 5.7) and abnormal NT-proBNP was 9.9% (95% CI, 5.8 to 14.1) versus 4.7% (95% CI, 3.2 to 6.2). Among survivors with a normal LVEF, abnormal baseline GLS and NT-proBNP identified anthracycline-exposed, IGHG-defined moderate-/high-risk survivors at a four-fold increased hazard of postbaseline cardiomyopathy (HR, 4.39 [95% CI, 2.46 to 7.83]; P < .001), increasing to a HR of 14.16 (95% CI, 6.45 to 31.08; P < .001) among survivors who received ≥250 mg/m2 of anthracyclines. Six years after baseline, AUCs for individual risk prediction were 0.70 for models with and 0.63 for models without GLS and NT-proBNP (P = .022). GLS and NT-proBNP should be considered for improved identification of survivors at high risk for future cardiomyopathy.

Prognostic Impact of Repeated NT-proBNP Measurements in Patients With Heart Failure With Reduced Ejection Fraction

BackgroundAlthough clinical studies have demonstrated the association between a single N-terminal pro–B-type natriuretic peptide (NT-proBNP) measurement and clinical outcomes in chronic heart failure, the biomarker is frequently measured serially in clinical practice. ObjectivesThe aim of this study was to determine the added prognostic value of repeated NT-proBNP measurements compared with single measurements alone for chronic heart failure patients. MethodsIn the GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study, 894 study participants with chronic heart failure with reduced ejection fraction were enrolled at 45 outpatient sites in the United States and Canada. Repeated NT-proBNP levels were measured over a 2-year study period. Associations between repeated NT-proBNP measurements and trial endpoints were assessed using a joint longitudinal and survival model. ResultsAfter adjustment for baseline covariates, each doubling of the baseline NT-proBNP level was associated with a HR of 1.17 (95% CI: 1.08-1.28; P = 0.0003) for the primary trial endpoint of cardiovascular death or heart failure hospitalization. Serial measurements increased the adjusted HR for the primary trial endpoint to 1.66 (95% CI: 1.50-1.84; P < 0.0001), and a similar increased risk was observed across secondary trial endpoints. In joint modeling, an increase in NT-proBNP occurred weeks before the onset of adjudicated events. ConclusionsRepeated NT-proBNP measurements are a strong predictor of outcomes in heart failure with reduced ejection fraction with an increase in concentration occurring well before event onset. These results may support routine NT-proBNP monitoring to assist in clinical decision making. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT]; NCT01685840)

Changes in Natriuretic Peptide Levels and Subsequent Kidney Function Decline in SPRINT

Rationale & ObjectiveNovel approaches to assessing kidney disease risk during hypertension treatment are needed given the uncertainty in how intensive blood pressure (BP) lowering impacts kidney outcomes. We determined whether longitudinal N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements during hypertension treatment are associated with kidney function decline. Study DesignProspective observational study. Setting& Participants: 8005 Systolic Blood Pressure Intervention Trial (SPRINT) participants with NT-proBNP measurements at baseline and 1 year. Exposure1-year change in NT-proBNP categorized as ≥25% decrease, ≥25% increase, and <25% change (stable). OutcomeAnnualized change in estimated glomerular filtration rate (eGFR) and ≥30% decline in eGFR. Analytical ApproachLinear mixed-effect and logistic regression models were used to evaluate the association of change in NT-proBNP with subsequent annualized change in eGFR and ≥30% decline in eGFR, respectively. Analyses stratified by baseline chronic kidney disease (CKD) status. ResultsCompared with stable 1-year NT-proBNP levels, a ≥25% decrease in NT-proBNP was associated with slower decline in eGFR in those with CKD (adjusted difference [% per year] =1.09 [95% CI, 0.35-1.83]) and without CKD (adjusted difference [% per year] =0.51 [95% CI, 0.21-0.81]; P for interaction =0.4). Meanwhile, ≥25% increase in NT-proBNP in those with CKD was associated with faster decline in eGFR (adjusted difference [% per year] = -1.04 [95% CI, -1.72 to -0.36]) and risk of ≥30% decline in eGFR (adjusted odds ratio: 1.44 [95% CI, 1.06-1.96]); associations were stronger in those with CKD versus without CKD (P for interactions =0.01 and <0.001, respectively). Relationships were similar irrespective of the randomized BP arm in SPRINT (P for interactions >0.2). LimitationsPersons with diabetes and proteinuria > 1 g/d were excluded. ConclusionsChanges in NT-proBNP during BP treatment are independently associated with subsequent kidney function decline, particularly in people with CKD. Studies should assess if dynamic NT-proBNP may be useful in monitoring kidney risk during hypertension treatment.

Abstract 18200: Prognostic Importance of Serial NT-proBNP Measurements Following High-Risk Mi: The PARADISE-MI Trial

Introduction: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a potent predictor of heart failure (HF) and death following myocardial infarction (MI). NT-proBNP levels change post MI. Hypothesis: Serial measurements of NT-proBNP add prognostic information. Aims: To investigate the prognostic importance of NT-proBNP two weeks after MI in PARADISE-MI and to identify predictors of week 2 NT-proBNP. Methods: Patients with MI and LVEF ≤40% and/or pulmonary congestion (n=5661) were randomized to sacubitril/valsartan or ramipril. Patients with NT-proBNP measured at week 2 (n=1057) were analyzed. Associations of week 2 NT-proBNP with subsequent clinical outcomes were evaluated with Cox models adjusted for baseline NT-proBNP, age, sex, atrial fibrillation (AF), LVEF, STEMI presentation, BMI, eGFR, high-sensitivity troponin T (hs-cTnT), time from presentation to randomization and treatment assignment. Results: Median NT-proBNP was 1425 [685, 2598] ng/L at week 2, declining 23% (95% CI, 20-26%) from baseline. Patients in the highest NT-proBNP quartile at week 2 (≥2616 ng/L) were older, had lower LVEF and eGFR, higher Killip class, more AF, and higher baseline NT-proBNP (all p≤0.05). Higher NT-proBNP at week 2 was independently associated with greater risk of CV death or incident HF (adjusted HR [aHR] 1.62 per log2; 95% CI, 1.30-2.03), HF hospitalization (aHR 1.96; 95% CI, 1.46-2.62) and all-cause death (aHR 1.86; 95% CI, 1.40-2.47). Higher baseline NT-proBNP and hs-cTnT, longer interval between presentation and randomization and female sex were associated with higher week 2 NT-proBNP levels while sacubitril/valsartan was associated with lower levels (Table). Conclusions: Patients with elevated NT-proBNP two weeks after high-risk MI are at greater risk of subsequent death or incident HF, even after adjusting for baseline level. Higher baseline NT-proBNP and hs-cTnT are predictive of higher week 2 NT-proBNP while sacubitril/valsartan decreases levels.

Cardiac Amyloid Detection by PET/CT Imaging of Iodine (124I) Evuzamitide (124I-p5+14): A Phase 1/2 Study

BackgroundThe noninvasive detection of cardiac amyloid, as well as deposits in other vital organs, is critical for early diagnosis and quantitative disease monitoring. Positron emission tomography is an intrinsically quantitative imaging modality suitable for high-resolution amyloid detection. ObjectivesThis study sought to evaluate the safety and efficacy of a novel amyloid-reactive peptide, designated p5+14, labeled with iodine-124 (124I), in patients with diverse types of systemic amyloidosis. MethodsIn a single-site, open label phase 1/2 study (NCT03678259), the safety, biodistribution, and sensitivity of a single intravenous infusion of 124I-evuzamitide was assessed in patients with systemic amyloidosis (n = 50), asymptomatic transthyretin sequence variant carriers (n = 2), and healthy volunteers (n = 5). Subjects were administered 1.4 ± 0.2 mg of 124I-evuzamitide (71.5 ± 12.4 MBq) and positron emission tomography/x-ray computed tomography images acquired at 5.2 hours (Q25-Q75: 4.9-5.4 hours) postinfusion. Images were assessed visually and semi-quantitatively for positive uptake of radiotracer in the heart and other major organs. ResultsUptake of 124I-evuzamitide in the heart and other abdominothoracic organs was consistent with the patient’s clinical presentation and the type of amyloidosis. The patient- and cardiac-associated sensitivity for imaging and clinical observations was 93.6% (95% CI: 82.8%-97.8%) and 96.2% (95% CI: 81.8%-99.8%), respectively. Semi-quantitative uptake of the radiotracer correlated significantly with serum N-terminal pro–B-type natriuretic peptide measurements in patients with light chain–associated amyloidosis. Cardiac uptake was not observed in any healthy volunteers. The agent was well tolerated, with 1 drug-related adverse event and no deaths. Conclusions124I-evuzamitide is an amyloid-binding radiotracer capable of detecting cardiac amyloid in patients with high sensitivity.

A-018 Biological Variation Estimates for N-terminal pro-B-type Natriuretic Peptide from Eight Healthy Turkish Women

Abstract Background B-type natriuretic peptide (BNP) and its precursor N-terminal pro-B-type natriuretic peptide (NT-proBNP) are released primarily by the ventricles in the heart in response to volume or pressure overload. Measurements of NT-proBNP are used as an aid in the diagnosis and assessment of severity of congestive heart failure (CHF). Within- (CVI) and between-subject (CVG) biological variation (BV) estimates for NT-proBNP are limited. Here biological variability (BV) estimates from eight apparently healthy Turkish women for NT-proBNP are provided. Methods Serum samples were collected weekly from 24 healthy subjects (12 male, 12 female) for 10 consecutive weeks and stored at −80 °C prior to analysis. Study participant samples were analyzed in duplicate within a single run using the Atellica® IM NT-proBNP (PBNP) assay* on the Atellica IM Analyzer. Outlier detection, variance homogeneity analyses, and trend analysis were performed followed by CV-ANOVA to determine BV and analytical variation (CVA) estimates with 95% CI. The asymmetrical reference change values (RCV) using the lognormal approach, index of individuality (II), and analytical performance specification (APS), based on the CVA estimate derived in our study, were also calculated. Results PBNP results from 11 males and 3 females were lower than the limit of quantitation (LoQ) of the assay (&amp;lt;35 pg/mL). The remaining male sample was not included in the analysis. One female sample was identified as an outlier between individuals and was excluded from the analysis. To fulfil criteria for variance homogeneity of the data from eight women, 7% of results were excluded. In total, 104 analytical results were included in the analysis. PBNP data for the female group was normally distributed, and no trends were identified by regression analysis. The BV estimates derived from females were CVI: 23.7%, (95% CI 19.0–30.4) and CVG: 8.22%, (95% CI 0.0–24.7). The CVA obtained from replicate test results was 11.2% (95% CI 9.4–13.9), which was lower than the desirable APS for imprecision. The II, calculated as the ratio of CVI/CVG, indicated a low individuality of PBNP (defined as II &amp;gt; 1.6). Thus, use of a population-based reference interval for interpreting serial PBNP measurements is more appropriate than use of the RCV. Conclusions This study provides updated BV estimates for NT-proBNP derived from a protocol consistent with European Federation of Clinical Chemistry and Laboratory Medicine recommendations. The availability of BV estimates allows for refined APS and associated II and RCV, which are applicable when using PBNP as an aid in the diagnosis and assessment of severity of congestive heart failure. *The products/features mentioned here are not commercially available in all countries. Their future availability cannot be guaranteed.

A-058 Frequency of Biochemical Assessment of Risk for Heart Failure among Diabetic Population

Abstract Background Diabetes remains a prevalent chronic health condition. Patients with diabetes have nearly twice the risk of developing heart failure as the general population and the American Diabetes Association recommends annual assessment by measuring N-terminal pro-B-type natriuretic peptide (NT-proBNP) or BNP among diabetic patients. We evaluated the frequency of biomarker assessment among our diabetic population. Methods Retrospective analysis of glycated hemoglobin (A1c) and NT-proBNP measured over a period of 21 months were performed. The frequency of NTproBNP assessment among patients with diagnostic A1c values were determined. Statical analysis were performed using Microsoft® Excel and NCSS® statistical software. Results A total of 74 973 A1c and 23 540 NT-proBNP measurements were performed during the study period. Among diabetics, 16% of patients received NT-proBNP testing with about 38% exhibiting elevated values. Conclusion This preliminary and retrospective study indicated that diabetic patients are receiving biochemical assessment for heart failure and that a significant number are of diagnostic value. It is not clear if other clinical modalities for heart failure assessment are in effect and if increased utility of biochemical assessment is required. Further studies are required to assess the utility among our patient’s population and on the best protocol to apply.

Natriuretic Peptide Normative Levels and Deficiency: The National Health and Nutrition Examination Survey

BackgroundNatriuretic peptides (NPs) are hormones with a range of key functions vital for cardiometabolic health. However, the reference ranges of NPs and the prevalence of NP deficiency in the healthy United States population remains poorly defined. ObjectivesThis study aims to establish the reference range for N-terminal pro–B-type natriuretic peptide (NT-proBNP) values and to assess the prevalence of NP deficiency in a nationally representative healthy United States population. MethodsHealthy participants with NT-proBNP measurements from the 1999-2004 National Health and Nutrition Examination Survey were included. Weighted multivariable-adjusted linear regression models were used to assess the adjusted percentage difference of NT-proBNP concentrations by sex and race and ethnicity. NP deficiency was defined as concentrations <2.5th percentile in the study cohort. ResultsAmong 18,145 individuals (median age: 33.9 years [IQR: 17.1-49.0 years], 49.8% males, and 68.5% non-Hispanic White individuals), females had similar NT-proBNP concentrations in the 1-10 years group (4.2% [95% CI: −3.3% to 12.2%]), and highest differences in the 20-30 years group (150.5% [95% CI: 123.5%-180.8%]) compared with males in their respective age groups. Compared with non-Hispanic White individuals, non-Hispanic Black individuals had lower NT-proBNP concentrations in the 1- to 10-years group (19.6% [95% CI: 10.7%-27.6%]), and these differences were most pronounced in the 30-40 years group (40.2% [95% CI: 33.7%-46.0%]). An estimated 9.1 million United States individuals had NP deficiency. NP deficiency was associated with a higher risk of cardiometabolic diseases such as hypertension, dyslipidemia, obesity, and insulin resistance. ConclusionsThis study establishes the normative NP concentrations across the lifespan of a healthy United States population.

Importance of the 'area under the curve' from serial NT-proBNP measurements during treatment with sacubitril/valsartan.

Serial assessment of natriuretic peptides is widely utilized in heart failure clinics. Uncertainty exists regarding the value of multiple natriuretic peptide measurements and how they might be best interpreted. Six hundred thirty-two patients with heart failure with reduced ejection fraction (<40%) and complete biomarker data were enrolled to receive sacubitril/valsartan. Patients underwent periodic study visits during 1-year follow-ups. Echocardiographic data and cardiac biomarkers, including N-terminal pro-B-type natriuretic peptide (NT-proBNP) were collected during study visits. Patients were categorized into three groups based on tertiles of baseline NT-proBNP levels. The area under the curve (AUC) of NT-proBNP measurements across study visits was calculated. Compared with patients with higher AUC (and thus higher concentrations over a longer period of time), those with lower AUC were younger, had a lower prevalence of chronic kidney disease, prior coronary artery bypass graft, atrial fibrillation, and higher body-mass index. A significant interaction existed between baseline NT-proBNP and subsequent AUC for predicting LVEF change across visits (P-value<0.001): among those with lower baseline NT-proBNP, similar improvements in left ventricular (LV) volumes LV ejection fraction, and LV mass index were observed across subsequent AUC (P-value>0.1). However, among those with higher baseline NT-proBNP, those with lower subsequent AUC had a greater improvement in cardiac remodelling indices (P-value<0.05). Serial NT-proBNP monitoring (integrating the totality of measurements as an AUC) during treatment with sacubitril/valsartan informs unique information regarding the future changes in cardiac remodelling indices, especially among those with higher NT-proBNP levels at baseline.

Cardiac Troponin T and NT-proBNP for Prediction of 30-Day Readmission or Death in Patients with Acute Dyspnea: Data from the Akershus Cardiac Examination 2 Study

Introduction: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) measurements are recommended in patients with acute dyspnea. We aimed to assess the prognostic merit of cTnT compared to NT-proBNP for 30-day readmission or death in patients hospitalized with acute dyspnea. Methods: We measured cTnT and NT-proBNP within 24 h in 314 patients hospitalized with acute dyspnea and adjudicated the cause of the index admission. Time to first event of readmission or death ≤30 days after hospital discharge was recorded, and cTnT and NT-proBNP measurements were compared head-to-head. Results: Patients who died (12/314) or were readmitted (71/314) within 30 days had higher cTnT concentrations (median: 32.6, Q1–Q3: 18.4–74.2 ng/L vs. median: 19.4, Q1–Q3: 8.4–36.1 ng/L; p for comparison <0.001) and NT-proBNP concentrations (median: 1,753.6, Q1–Q3: 464.2–6,862.0 ng/L vs. median 984, Q1–Q3 201–3,600 ng/L; for comparison p = 0.027) compared to patients who survived and were not readmitted. cTnT concentrations were associated with readmission or death within 30 days after discharge both in the total cohort (adjusted hazard ratio [aHR]: 1.64, 95% confidence interval [CI]: 1.30–2.05) and in patients with heart failure (HF) (aHR: 1.58, 95% CI: 1.14–2.18). In contrast, NT-proBNP concentrations were not associated with short-term events, neither in the total cohort (aHR: 1.10, 95% CI: 0.94–1.30) nor in patients with adjudicated HF (aHR: 1.06, 95% CI: 0.80–1.40). Conclusion: cTnT concentrations are associated with 30-day readmission or death in patients hospitalized with acute dyspnea, as well as in patients adjudicated HF.

Evaluation of the Correlation of Pulmonary Arterial Hypertension (PAH) with the Pulmonary Artery Trunk Diameter and Serum Level of N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) in Patients with PAH

Background: Due to its non-specific symptoms, pulmonary arterial hypertension (PAH) is difficult to diagnose via non-invasive methods. Various diagnostic tests are required to evaluate PAH patients. The increased diameter of the main pulmonary artery in computed tomography (CT) imaging represents a high probability of PAH. Moreover, N-terminal pro B-type natriuretic peptide (NT-proBNP) and pro B-type natriuretic peptide (proBNP) can be considered as prognostic predictors in patients with PAH. Objectives: This study aimed to evaluate the correlation of CT-based main pulmonary artery diameter (MPAD) and the serum level of NT-proBNP (as a strong pro-inflammatory factor) with the severity of PAH in echocardiography among patients with PAH. Patients and Methods: In this cross-sectional study, a total of 63 hospitalized patients with PAH due to chronic obstructive pulmonary disease were recruited from 2019 to 2020 after initial evaluations and collection of serum NT-proBNP measurements and echocardiographic findings. On the chest CT scans, the largest diameter of the pulmonary artery trunk was determined, and then, correlation of CT-based MPAD with both PAH severity on echocardiography and NT-proBNP level in patients with PAH were evaluated. Results: The results of the present study on 63 patients (70% male; mean age, 67.02 years) showed a significant positive correlation between the MPAD and NT-proBNP level (r = 0.444, P &lt; 0.001). Moreover, a significant positive relationship was observed between the pulmonary artery pressure (PAP) and NT-proBNP (r = 0.353, P = 0.005) and also between MPAD and PAP (r = 0.306, P = 0.015). In PAH patients, the mean values of MPAD, PAP, and NT-proBNP were 32.58 mm, 47.9 mmHg, and 6563 pg/mL, respectively. Conclusion: Considering the significant positive correlation between PAP, MPAD, and NT-proBNP level in subgroup comparisons based on MPAD and PAP, if the MPAD is abnormal on CT scan, additional echocardiographic assessments and serum NT-proBNP measurements can be helpful.

Independent and joint associations between the triglyceride-glucose index and NT-proBNP with the risk of adverse cardiovascular events in patients with diabetes and acute coronary syndrome: a prospective cohort study

BackgroundElevated triglyceride-glucose (TyG) index and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are independently associated with increased risk of major adverse cardio-cerebral events (MACCEs) in diabetic patients with the acute coronary syndrome (ACS), but have not been evaluated jointly. We sought to investigate the independent and joint association of the TyG index and NT-proBNP with MACCEs risk.MethodsData from 5046 patients with diabetes and ACS were recorded in the Cardiovascular Center Beijing Friendship Hospital Database Bank between 2013 and 2021, including measurements of fasting triglycerides, plasma glucose, and NT-proBNP. The TyG index was calculated as Ln (fasting triglycerides [mg/dL] × fasting plasma glucose [mg/dL]/2). Associations of the TyG index and NT-proBNP with MACCEs risk were assessed using flexible parametric survival models.ResultsDuring 13589.9 person-years of follow-up, 985 incident MACCEs of the 5046 patients (65.6 years of age and 62.0% men) were observed. Elevated TyG index (HR: 1.18; 95% CI 1.05‒1.32 per 1 unit increase) and NT-proBNP categories (HR: 1.95; 95% CI: 1.50‒2.54 for > 729 pg/ml compared to < 129 pg/ml) were independently associated with MACCEs risk in the fully adjusted model. According to the joint categories of the TyG index and NT-proBNP, patients with the TyG index > 9.336 and NT-proBNP > 729 pg/ml were at the highest risk of MACCEs (HR: 2.45; 95% CI 1.64‒3.65) than the ones with TyG index < 8.746 and NT-proBNP < 129 pg/ml. The test for interaction was not significant (Pinteraction = 0.49). Incorporating these two biomarkers into the established clinical model, the Global Registry of Acute Coronary Events (GRACE) risk score, resulted in a significant improvement in risk stratification.ConclusionsThe TyG index and NT-proBNP were independently and jointly associated with the risk of MACCEs in patients with diabetes and ACS, suggesting that patients with both markers elevated should be aware of the higher risk in the future.

A Brief Report on Utility of N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) in Screening Patients at Risk of Atrial Fibrillation and Stroke

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a prohormone that is produced and released by the heart (ventricles) in response to alteration in pressure/strain/volume.[1-3] It is used as a biomarker of cardiac function and is involved in the regulation of fluid and electrolyte balance.1-3 When the heart is under stress or is experiencing decreased blood flow, the ventricular myocardium releases the precursor molecule proBNP, which is then cleaved (by a membrane-bound enzyme called corin) into B-type natriuretic peptide (BNP) and NT-proBNP in equimolar amounts.4,5 BNP is secreted into the blood and promotes vasodilation and diuresis, while NT-proBNP serves as a stable marker of cardiac function and is involved in the regulation of fluid and electrolyte balance.6,7 NT-proBNP synthesized in the cardiac ventricles as a prepropeptide (134 amino acids) undergoes several post-translational modifications, including signal peptide cleavage, propeptide cleavage, and glycosylation, before being released as the mature 76-amino acid NT-proBNP molecule.4,5 NT-proBNP is secreted into the bloodstream and is cleared primarily by the kidneys. NT-proBNP levels are influenced by a variety of factors, including age, sex, kidney function, and cardiac disease.8,9 Elevated levels of NT-proBNP are associated with an increased risk of cardiovascular events, such as heart failure, atrial fibrillation and stroke, and can be used as a diagnostic tool to identify individuals at risk of these conditions.6,10-12 The concentration NT-proBNP can be measured in serum/ plasma samples. The assays for NT-proBNP measurement typically use immunoassay techniques, such as Enzyme-Linked Immunosorbent Assay (ELISA) or Chemiluminescence Immunoassay (CLIA), which rely on the binding of specific antibodies to the NT-proBNP molecule. These assays are highly sensitive and specific, with low limits of detection and high precision, making them valuable tools for the diagnosis and management of cardiovascular disease.11,12.

Effects of Systematic Atrial Fibrillation Screening According to N-Terminal Pro-B-Type Natriuretic Peptide: a Secondary Analysis of the Randomized LOOP Study.

Research suggests N-terminal pro-B-type natriuretic peptide (NT-proBNP) to be a strong predictor of incident atrial fibrillation (AF) and stroke. However, its utility in AF screening remains unknown. This study aimed to investigate NT-proBNP as a potential marker for screening efficacy with respect to AF yield and stroke prevention. In the LOOP Study, 6004 AF-naïve individuals aged 70-90 years with additional stroke risk factors were randomized 1:3 to either continuous screening with implantable loop recorder (ILR) and anticoagulation initiation upon detection of AF episodes ≥6 minutes, or usual care (Control). This post-hoc analysis included the study participants with available NT-proBNP measurement at baseline. A total of 5819 participants were included (mean age 74.7 years (standard deviation, 4.1), 47.5%females). The median NT-proBNP level was 15 pmol/L [interquartile range: 9-28], corresponding to 125 pg/mL [interquartile range: 76-233]. NT-proBNP above median was associated with an increased risk of AF diagnosis both in the ILR group (hazard ratio (HR) 1.84 [95% confidence interval (CI): 1.51-2.25]) and the Control group (HR 2.79 [95% CI: 2.30-3.40]). Participants with NT-proBNP above median were also at higher risk of clinical events compared with those having lower levels (HR 1.21 [95% CI: 0.96-1.54] for stroke or systemic embolism (SE), 1.60 [95% CI: 1.32-1.95] for stroke/SE/cardiovascular death, and 1.91 [95% CI: 1.61-2.26] for all-cause death). Compared with usual care, ILR screening was associated with significant reductions in stroke/SE and stroke/SE/cardiovascular death among participants with NT-proBNP above median (HR 0.60 [95% CI: 0.40-0.90] and 0.70 [95% CI: 0.53-0.94], respectively), but not among those with lower levels (pinteraction=0.029 for stroke/SE and 0.045 for stroke/SE/cardiovascular death). No risk reduction in all-cause death was observed in either NT-proBNP subgroup for ILR versus Control (pinteraction=0.68). Analyzing NT-proBNP as a continuous variable yielded similar findings. In an elderly population with additional stroke risk factors, ILR screening for AF was associated with a significant reduction in stroke risk among individuals with higher NT-proBNP levels, but not among those with lower levels. These findings should be considered hypothesis-generating and warrant further study before clinical implementation.

Heart Rate Variability Impairment Is Associated with Right Ventricular Overload and Early Mortality Risk in Patients with Acute Pulmonary Embolism.

The association between heart rate variability (HRV) and mortality risk of acute pulmonary embolism (APE), as well as its association with right ventricular (RV) overload is not well established. We performed an observational study on consecutive patients with confirmed APE. In the first 48 h after admission, 24 h Holter monitoring with assessment of time-domain HRV, echocardiography and NT-proBNP (N-terminal pro-B-type natriuretic peptide) measurement were performed in all participants. We pre-examined 166 patients: 32 (20%) with low risk of early mortality, 65 (40%) with intermediate-low, 65 (40%) with intermediate-high, and 4 (0.02%) in the high risk category. The last group was excluded from further analysis due to sample size, and finally, 162 patients aged 56.3 ± 18.5 years were examined. We observed significant correlations between HRV parameters and echocardiographic signs of RV overload. SDNN (standard deviation of intervals of all normal beats) correlated with echocardiography-derived RVSP (right ventricular systolic pressure; r = -0.31, p = 0.001), TAPSE (tricuspid annulus plane systolic excursion; r = 0.21, p = 0.033), IVC (inferior vena cava diameter; r = -0.27, p = 0.002) and also with NT-proBNP concentration (r = -0.30, p = 0.004). HRV indices were also associated with APE risk stratification, especially in the low-risk category (r = 0.30, p = 0.004 for SDNN). Univariate and multivariate analyses confirmed that SDNN values were associated with signs of RV overload. In conclusion, we observed a significant association between time-domain HRV parameters and echocardiographic and biochemical signs of RV overload. Impaired HRV parameters were also associated with worse a clinical risk status of APE.

Efficacy of omecamtiv mecarbil in heart failure with reduced ejection fraction according to N-terminal pro-B-type natriuretic peptide level: insights from the GALACTIC-HF trial.

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is predictive of both outcomes and response to treatment in patients with heart failure with reduced ejection fraction (HFrEF). The aim of this study was to examine the effect of the cardiac myosin activator omecamtiv mecarbil according to baseline NT-proBNP level in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure trial (GALACTIC-HF). The primary outcome was the composite of a worsening heart failure event (urgent clinic visit, emergency department visit, or hospitalization) or cardiovascular death. We prespecified analysis of the effect of treatment according to baseline NT-proBNP (≤ median, > median), excluding individuals with atrial fibrillation/flutter (AF/AFL). Of the 8232 patients analysed, 8206 had an available baseline NT-proBNP measurement. Among the 5971 patients not in AF/AFL, the median (Q1-Q3) NT-proBNP level was 1675 (812-3579) pg/ml. Hazard ratios (HR) for the effect of omecamtiv mecarbil, compared with placebo, for the primary endpoint in patients without AF/AFL were: ≤ median 0.94 (95% confidence interval [CI] 0.80-1.09), > median 0.81 (0.73-0.90) (p-interaction=0.095); for the overall population (including patients with AF/AFL) the HRs were ≤ median 1.01 (0.90-1.15) and > median 0.88 (0.80-0.96) (p-interaction=0.035). There was an interaction between treatment and NT-proBNP, examined as a continuous variable, with greater effect of omecamtiv mecarbil on the primary outcome in patients with a higher baseline NT-proBNP (p-interaction=0.086). In GALACTIC-HF, the benefit of omecamtiv mecarbil appeared to be larger in patients with higher baseline NT-proBNP levels, especially in patients without AF/AFL. ClinicalTrials.gov Identifier NCT02929329; EudraCT number, 2016-002299-28.