B-type Natriuretic Peptide Concentrations Research Articles

Determinants of left atrioventricular coupling index: The Multi-Ethnic Study of Atherosclerosis (MESA)

Recent studies have described a novel left atrioventricular coupling index (LACI), which had a better prognostic value in predicting cardiovascular events than individual left atrial (LA) or left ventricular (LV) variables. To identify determinants of LACI and its 10-year annual change (ΔLACI), measured by cardiac magnetic resonance (CMR), and to better understand the variables governing this left atrioventricular coupling. In the Multi-Ethnic Study of Atherosclerosis, 2112 study participants, free from cardiovascular disease at baseline, had LACI assessed by CMR imaging at baseline (LACIBaseline; 2000-2002) and 10 years later (2010-2012). The LACI was defined as the ratio of LA to LV end-diastolic volumes. Linear regression analyses were performed to identify independent determinants of LACIBaseline and ΔLACI. In the 2112 participants (mean age 58.8±9.1 years; 46.6% male), after adjustment for all covariates, age was independently associated with LACIBaseline (R2=0.10, slope=0.16) and ΔLACI (R2=0.15, slope=0.008; both P<0.001). African Americans had the highest LACIBaseline value (18.0±7.7%). Although there was no difference in LACIBaseline between women and men (P=0.19), ΔLACI was higher in women (1.0±1.1 vs 0.8±1.1%/year; P<0.001). Diabetes and higher body mass index (BMI) were independently associated with LACIBaseline (both P<0.001). LACIBaseline was independently associated with LV myocardial fibrosis markers (native T1: R2=0.11, slope=0.09 [P=0.038]; extracellular volume: R2=0.08, slope=0.28 [P=0.035]) and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) concentration (R2=0.10, slope=-1.11; P<0.001), but was not associated with interleukin 6 or high-sensitivity C-reactive protein. Age, sex, ethnicity, diabetes and BMI were independent determinants of LACI. LACI was independently associated with myocardial fibrosis markers and NT-proBNP concentration.

B‐Type Natriuretic Peptide and Long‐Term Cardiovascular Mortality in Patients With Coronary Heart Disease

BackgroundThe plasma concentration of B‐type natriuretic peptide (BNP) is a strong predictor of adverse cardiovascular events. The aim of this study was to determine whether the association between plasma BNP concentration and cardiovascular mortality is sustained or diminishes with increasing time after BNP is measured.Methods and ResultsSix thousand seven hundred forty patients with a history of myocardial infarction or unstable angina who participated in the LIPID (Long‐Term Intervention with Pravastatin in Ischemic Disease) trial had plasma BNP concentration measured at baseline and after 1 year. Associations with cardiovascular mortality were evaluated in landmark analyses 1 to <5, 5 to <10, and 10 to 16 years after randomization. There were 1640 cardiovascular deaths. The cardiovascular mortality rate increased progressively from 10.2 to 19.1 to 26.3/1000 patient‐years from 1 to <5, 5 to <10, and 10 to 16 years after baseline, respectively. The average of baseline and 1‐year BNP concentration was more strongly associated with cardiovascular mortality compared with baseline or 1‐year BNP only. The hazard ratio (HR) for cardiovascular death associated with each doubling of average BNP concentration was similar during years 1 to <5 (HR, 1.53 [95% CI, 1.44–1.63]), years 5 to <10 (HR, 1.52 [95% CI, 1.44–1.60]), and years 10–16 (HR, 1.43 [95% CI, 1.36–1.50]), P<0.0001 for all.ConclusionsBNP concentration remains an independent predictor of cardiovascular mortality more than a decade after it is measured. Because of random variation in plasma concentrations, the average of >1 BNP measurement improves long‐term risk prediction.

Serum TP53 Protein Level as a Sensitive Biomarker for the Diagnosis of Myocardial Damage in Children.

BackgroundHigh levels of TP53 protein can lead to apoptosis of myocardial cells. However, TP53 protein influence of myocardial damage remains unclear. This prospective study investigated the involvement of TP53 protein in secondary myocardial damage in children up to 18 years of age.Material/MethodsSerum TP53 protein, N-terminal prohormone B-type natriuretic peptide (NT-ProBNP), cardiac troponin-I (cTnI), and creatine kinase isoenzyme MB (CK-MB) concentrations were measured in 50 hospitalized patients with secondary myocardial damage, 50 hospitalized patients without myocardial damage, and 50 healthy individuals (control). Cardiac damage was diagnosed based on cTnI, NT-ProBNP, and CK-MB levels, with electrocardiographic evidence as the reference. The appropriate cut-off value of TP53 protein for secondary myocardial damage was analyzed by receiver operating characteristic (ROC) curves.ResultsThe serum TP53 protein, NT-ProBNP, cTnI, and CK-MB concentrations of the patients with and without myocardial damage were 10.20±1.20 and 0.30±0.10 ng/L, 505.30 and 107.8 ng/L, 0.23±0.13 and 0.02±0.01 μg/L, and 28.30±5.13 and 12.24±4.29 IU/L, respectively. For the 50 patients with myocardial damage, the area under the ROC curve for serum TP53 protein, NT-ProBNP, cTnI, and CK-MB concentrations were 0.89 (95% CI: 0.81–0.95), 0.83 (95% CI: 0.77–0.91), 0.92 (95% CI: 0.84–0.97), and 0.85 (95% CI: 0.78–0.93), respectively, and the diagnostic cut-off values were 12.00 ng/L, 500.00 ng/L, 0.16 μg/L, and 27.00 IU/L, respectively, with positive likelihood ratios of 20.8, 13.2, 24.6, and 15.6.ConclusionsTP53 protein is a valid biomarker of secondary myocardial damage in pediatric patients and can be diagnostic.

Sex and Race Differences in N-Terminal Pro–B-type Natriuretic Peptide Concentration and Absolute Risk of Heart Failure in the Community

Sex- and race-based differences in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are poorly understood. Clinical decisions are often informed by absolute-as opposed to relative-risk, but absolute risk of incident heart failure (HF) associated with NT-proBNP concentration across these important demographic categories is unclear. To determine whether physiologic determinants of NT-proBNP concentrations account for sex and race differences, and to more uniformly predict HF risk using NT-proBNP in these demographic subgroups. In the longitudinal Atherosclerosis Risk in Communities epidemiologic prospective community-based cohort study, the association of NT-proBNP concentration with relative and absolute risk of HF by sex- and race-based categories was assessed at study visit 2 (1990-1992) and study visit 5 (2011-2013) using Cox and Poisson regression. These data were analyzed from June 2018 to October 2021. The contribution of clinical, anthropometric, echocardiographic, and laboratory parameters to sex- and race-based differences in NT-proBNP concentration was assessed at visit 5 using linear regression. Participants included were free of HF in midlife (visit 2; a total of 12 750 participants) and late life (visit 5; a total of 5191 participants). NT-proBNP concentration. Incident HF or death. Among the 5191 HF-free participants at visit 5, the mean (SD) age was 76.0 (5.2) years, 2104 (41%) were male, 1043 (20%) were Black, and the median (IQR) NT-proBNP concentration was 124 (64-239) pg/. In both midlife and late life, NT-proBNP concentration was lowest in Black men (median [IQR] concentration: visit 2, 30 [14-67] pg/mL; visit 5, 74 [34-153] pg/mL) and highest in White women (median [IQR] concentration: visit 2, 70 [42-111] pg/mL; visit, 5, 154 [82-268] pg/mL). Sex and race differences in NT-proBNP concentration persisted after accounting for age, income, education, area deprivation index, cardiovascular diseases, left ventricular structure (LV), LV function, LV wall stress, weight and fat mass, and estimated glomerular filtration rate. Substantial differences in the absolute risk of incident HF or death existed across the sex- and race-based categories at any NT-proBNP concentration (eg, 7-fold [rate ratio, 6.7; 95% CI, 4.6-9.9] and 3-fold [rate ratio, 2.7; 95% CI, 1.7-4.1] difference at visit 2 and visit 5, respectively, at guideline-recommended thresholds) with higher risk consistently observed among Black men and lower risk in White women. Results were replicated in a cohort of participants from the Cardiovascular Health Study. In this study, sex- and race-based differences in NT-proBNP persisted after accounting for known physiologic determinants. Absolute risk associated with a given value of NT-proBNP varied substantially by sex and race. Consideration of NT-proBNP values in the context of sex and race allows for more uniform prediction of absolute risk across important demographic subgroups.

Stress-Delta B-Type Natriuretic Peptide Does Not Exclude ACS in the ED.

There are many detectable changes in circulating biomarkers in the setting of myocardial ischemia. We hypothesize that there are associated changes in circulating B-type natriuretic peptide (BNP) level after stress-induced myocardial ischemia, which can be used for emergency department (ED) acute coronary syndrome (ACS) risk stratification. In a prospective study, we enrolled 340 patients over the age of 30 receiving an exercise echocardiography stress test in an ED observational unit for suspected ACS. We collected blood samples at baseline and at 2 and 4 h post-stress test, measuring the relative and absolute changes (stress-delta) in plasma BNP concentrations. In addition, patients were contacted at 90 days and at 1 year posttest for a follow-up. We calculated the diagnostic test characteristics of stress-delta BNP for a composite outcome of ischemic imaging on stress echocardiogram, nonelective percutaneous coronary intervention, coronary artery bypass graft surgery, subsequent acute myocardial infarction, or cardiac death at 1 year via a logistic regression. We analyzed the 2-h BNP concentrations using an ANOVA model to adjust for the baseline BNP level. Baseline and 2-h post-stress BNP were both higher in the positive outcome group, but the stress-delta BNP was not. Stress-delta BNP had a sensitivity and specificity, respectively, of 53% and 76% at 2 h and 67% and 68% at 4 h. It was noted that patients with the composite outcome had a higher baseline BNP level. BNP stress-deltas are poor diagnostic means for ACS risk stratification, but resting BNP remains a promising prognostic tool for ED patients with suspected ACS.

Heterogeneity Of Early B-type Natriuretic Peptide Change In HFrEF Patients Treated With Sacubitril/Valsartan

<h3>Introduction</h3> Through inhibition of neprilysin, sacubitril/valsartan (Sac/Val), an angiotensin receptor neprilysin inhibitor (ARNI), may cause initial increase in B-type natriuretic peptide (BNP) concentrations. The frequency, variability, and predictors of BNP rise during treatment of heart failure with reduced ejection fraction (HFrEF) from Sac/Val are not well-described. <h3>Hypothesis</h3> Changes in BNP after initiation of Sac/Val in HFrEF are variable and correlate with changes in NT-proBNP and ucGMP. <h3>Methods</h3> We classified BNP changes from baseline (pre Sac/Val) to Weeks 4 and12 among 367 patients treated with Sac/Val (regardless of dose) in an individual patient data analysis pooled from the EVALUATE-HF (n=221) and PROVE-HF (n=146) studies. Clinical predictors of BNP changes to Week 12 were analyzed in linear regression models and correlations with changes in NT-proBNP and ucGMP were examined using Spearman's rank correlation coefficient (rho). <h3>Results</h3> Across the two trials, median [IQR] concentration of BNP at Baseline, Week 4 and Week 12 was 145 [55, 329], 136 [50, 338] and 135 [51, 299] ng/L, respectively. There was no significant change from baseline to Week 4 (0% [-30%, +41%], p=0.36) or Week 12 (+1% [-36%, +50%], p=0.97). In adjusted analyses, predictors of BNP rise were similar to those of NT-proBNP rise and included atrial fibrillation, worse renal function, lower BMI, and lower concentrations of BNP/NT-proBNP at baseline (<b>Figure</b>). Change in BNP was strongly and linearly associated with change in NT-proBNP (rho=0.81, p<0.001), and the median [IQR] NT-proBNP change/BNP change was 66% [51%, 86%] (<b>Figure</b>). In contrast, change in BNP was only weakly associated with change in ucGMP (rho=0.19, p<0.001), and increases in ucGMP were observed regardless of whether BNP was decreased (+11% [-34%, +115%]), unchanged (+34% [-15%, +205%]), or increased (+57% [-12%, +14%]). <h3>Conclusions</h3> In this pooled analysis, following initiation of Sac/Val in HFrEF there was no significant overall increase in BNP concentrations. Early changes in BNP correlated closely with change in NT-proBNP but weakly with changes in ucGMP. Patients treated with Sac/Val demonstrate increase in ucGMP regardless of the BNP trajectory. These data argue against use of BNP rise as a biomarker of Sac/Val efficacy in HFrEF

Diuretics Versus Volume Expansion in the Initial Management of Acute Intermediate High-Risk Pulmonary Embolism.

The very early management of pulmonary embolism (PE), a part from antithrombotic treatment, has been little studied. Our aim was to compare the effects of diuretic therapy (DT) versus volume expansion (VE) in patients hospitalized for PE with RV dysfunction. We conducted a randomized open-label multicentric study including patients with intermediate high-risk PE. Patients were randomized between diuretics or saline infusion. The primary endpoint was time to troponin (Tp) normalization. Secondary endpoints were time to normalization of B-type natriuretic peptide (BNP), changes in echocardiographic RV function parameters and treatment tolerance. Sixty patients presenting intermediate high-risk PE were randomized. Thirty received DT and 30 VE. We noted no changes in Tp kinetics between the two groups. In contrast, faster normalization of BNP was obtained in the DT group: 56 [28-120] vs 108 [48-144] h: p = 0.05, with a shorter time to 50%-decrease from peak value 36 [24-48] vs 54 [41-67] h, p = 0.003 and a higher rate of patients with a lower BNP concentration within the first 12h (42% vs 12% p < 0.001). RV echocardiographic parameters were unchanged between the groups. One dose 40mg furosemide was well-tolerated and not associated with any serious adverse events. In the acute management of intermediate high-risk PE, initial therapy including diuretic treatment is well-tolerated and safe. Although changes in Tp kinetics and echocardiographic RV dysfunction parameters did not differ, normalization of BNP is achieved more quickly in the DT group. This finding, which need to be confirmed in trials with clinical end points, may reflects a rapid improvement in RV function using one dose 40mg furosemide. Clinical Trial Registration NCT02531581.

Quality Indicators in Patient Referral Documents for Heart Failure in Japan.

This study examined quality indicators (QIs) for heart failure (HF) in patients' referral documents (PRDs).We conducted a nationwide questionnaire survey to identify information that general practitioners (GPs) would like hospital cardiologists (HCs) to include in PRDs and that HCs actually include in PRDs. The percentage of GPs that desired each item included in PRDs was converted into a deviation score, and items with a deviation score of ≥ 50 were defined as QIs. We rated the quality of PRDs provided by HCs based on QI assessment.We received 281 responses from HCs and 145 responses from GPs. The following were identified as QIs: 1) HF cause; 2) B-type natriuretic peptide (BNP) or N-terminal pro-BNP concentration; 3) left ventricular ejection fraction or echocardiography; 4) body weight; 5) education of patients and their families on HF; 6) physical function, and 7) functions of daily living. Based on QI assessment, only 21.7% of HCs included all seven items in their PRDs. HCs specializing in HF and institutions with many full-time HCs were independently associated with including the seven items in PRDs.The quality of PRDs for HF varies among physicians and hospitals, and standardization is needed based on QI assessment.

Surrogate markers of gut dysfunction are related to heart failure severity and outcome–from the BIOSTAT-CHF consortium

The contribution of gut dysfunction to heart failure (HF) pathophysiology is not routinely assessed. We sought to investigate whether biomarkers of gut dysfunction would be useful in assessment of HF (eg, severity, adverse outcomes) and risk stratification. A panel of gut-related biomarkers including metabolites of the choline/carnitine- pathway (acetyl-L-carnitine, betaine, choline, γ-butyrobetaine, L-carnitine and trimethylamine-N-oxide [TMAO]) and the gut peptide, Trefoil factor-3 (TFF-3), were investigated in 1,783 patients with worsening HF enrolled in the systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) cohort and associations with HF severity and outcomes, and use in risk stratification were assessed. Metabolites of the carnitine-TMAO pathway (acetyl-L-carnitine, γ-butyrobetaine, L-carnitine, and TMAO) and TFF-3 were associated with the composite outcome of HF hospitalization or all-cause mortality at 3 years (hazards ratio [HR] 2.04-2.93 [95% confidence interval {CI} 1.30-4.71] P≤ .002). Combining the carnitine-TMAO metabolites with TFF-3, as a gut dysfunction panel, showed a graded association; a greater number of elevated markers was associated with higher New York Heart Association class (P< .001), higher plasma concentrations of B-type natriuretic peptide (P< .001), and worse outcome (HR 1.90-4.58 [95% CI 1.19-6.74] P≤ 0.008). Addition of gut dysfunction biomarkers to the contemporary BIOSTAT HF risk model also improved prediction for the aforementioned composite outcome (C-statistics P≤ .011, NRI 13.5-21.1 [95% CI 2.7-31.9] P≤ .014). A panel of biomarkers of gut dysfunction showed graded association with severity of HF and adverse outcomes. Biomarkers as surrogate markers are potentially useful for assessment of gut dysfunction to HF pathophysiology and in risk stratification.

Inverse Regulation of Serum Osteoprotegerin and B-Type Natriuretic Peptide Concentrations by Free Fatty Acids Elevation in Young Healthy Humans.

Osteoprotegerin (OPG) and B-type natriuretic peptide (BNP) are cardiovascular risk factors, interrelated with each other, with possible associations with insulin sensitivity and glucose homeostasis. The aim of this study was to assess association between OPG and BNP concentrations in a young healthy population, their relation to insulin sensitivity and obesity and their regulation by hyperinsulinemia and serum free fatty acids (FFA) elevation. The study group consisted of 59 male volunteers, 30 of whom were of a normal weight (BMI < 25 kg/m2), and 29 were overweight/obese (BMI > 25 kg/m2). Insulin sensitivity was assessed with the 2-h hyperinsulinemic-euglycemic clamp (HEC). In the subgroup of 20 subjects, the clamp was prolonged to 6 h. After one week, another 6-h clamp, with concurrent Intralipid/heparin infusion, was performed. Serum OPG was positively associated with insulin sensitivity (p = 0.002) and negatively with BMI (p = 0.019) and serum BNP (p = 0.025). In response to 6-h hyperinsulinemia, circulating BNP decreased (p < 0.001). In response to HEC with Intralipid/heparin infusion, OPG decreased (p < 0.001) and BNP increased (p < 0.001). Our data show that OPG and BNP are differentially regulated by FFA, which suggests their association with lipid-induced insulin resistance. The assessment of these cardiovascular risk factors should take into account both long-term and short-term effects associated with insulin resistance.

Left bundle branch pacing in heart failure patients with left bundle branch block: A systematic review and meta-analysis.

The clinical benefit of cardiac resynchronization therapy (CRT) in heart failure patients with left bundle branch block (LBBB) has been demonstrated. However, a nonresponse rate of CRT nearly 1/3. Recent studies have reported left bundle branch pacing (LBBP) has achieved remarkable effect in CRT. This study aim to explore the efficacy and safety of LBBP in heart failure patients with LBBB. We searched PubMed, Cochrane Library, Web of science, and CNKI databases for studies about LBBP in heart failure patients with LBBB. QRS duration (QRSd), New York Heart Association (NYHA) classification, B-type natriuretic peptide (BNP) concentration, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), pacing threshold and other related data were extracted and summarized. A total of 6 studies were included, and the success rate of LBBP was 93.2%. Compared with baseline, LBBP could shorten QRSd (MD=61.23, 95% CI: 58.21-64.25, p<.01). Echocardiographic parameters including LVEF and LVEDD significantly improved (both with p<.01). Clinical outcomes including NYHA classification and BNP dramatically reduced (both with p<.01). Compared with biventricular pacing (BVP), LBBP could further improve QRSd, LVEF, LVEDD, and NYHA classification (all with p<.01). However, the pacing threshold at follow-up was 0.06 V higher than that at baseline (p<.01), and the incidence of complications was 2.4%. LBBP is effective and safe in heart failure patients with LBBB, whether it is better than BVP needs to be verified by randomized controlled trials.

Early B-Type Natriuretic Peptide Change in HFrEF Patients Treated With Sacubitril/Valsartan: A Pooled Analysis of EVALUATE-HF and PROVE-HF

ObjectivesThis study assessed changes in B-type natriuretic peptide (BNP) among patients with heart failure with reduced ejection fraction (HFrEF) treated with sacubitril/valsartan (Sac/Val) according to standard prescribing information. BackgroundThrough inhibition of neprilysin, Sac/Val may increase BNP concentrations. MethodsIn an individual patient analysis from the EVALUATE-HF (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction) (n = 221) and the PROVE-HF (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes) (n = 146) studies, we examined changes in BNP, N-terminal pro-BNP (NT-proBNP), and urinary cyclic guanosine monophosphate (ucGMP) from baseline to week 4 and week 12. ResultsMedian (IQRs) concentration of BNP at baseline, week 4, and week 12 were 145 [IQR: 55-329], 136 [IQR: 50-338], and 135 [IQR: 51-299] ng/L, respectively. There was no significant change from baseline to week 4 (0% [−30% to +41%]; P = 0.36) or week 12 (+1% [−36% to +50%]; P = 0.97). By week 12, one-half of the study participants had a BNP decline. There was no association between Sac/Val dose and BNP changes. Change in BNP was directly associated with change in NT-proBNP (rho: = 0.81; P < 0.001), which decreased by −30% (−50% to −8%) and −32% (−54% to −1%) to weeks 4 and 12 (P < 0.001 for both). In contrast, change in BNP was only weakly associated with change in ucGMP (rho: = 0.19; P < 0.001). Increases in ucGMP were observed regardless of whether BNP was decreased (+11% [−34% to +115%]), unchanged (+34% [−15% to +205%]), or increased (+57% [−12% to +14%]). ConclusionsIn this pooled analysis of patients with HFrEF with standard indications for Sac/Val treatment, there was no significant overall increase in BNP concentrations, and patients demonstrated increase in ucGMP regardless of the trajectory of BNP change. (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction [EVALUATE-HF]; NCT02874794) (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).

IDENTIFYING PATIENTS AT HIGH RISK OF MORTALITY AND READMISSION AFTER DECOMPENSATED HEART FAILURE: PROGNOSTIC SIGNIFICANCE OF 1-MONTH POSTDISCHARGE BNP

Background: In individuals with congestive heart failure, B-type natriuretic peptide (BNP) levels may indicate future cardiovascular complications. The majority of research has linked baseline B-type natriuretic peptide (BNP) levels to lengthy effects. The prognostic value of 1-month post-discharge BNP concentrations in acute heart failure is little understood. Method: Patients who were hospitalized repeatedly for deteriorating heart failure were included. BNP levels were evaluated at admission, prior to discharge, and 15 days after discharge. For 6 months, patients were monitored for mortality and readmission to the hospital as endpoints. Results: The heart failure study involved a total of 100 patients, with an average age of 60.7 ± 13.7 years. 80 patients (53%) experienced acute heart failure as a result of acute coronary syndrome, while the remaining 20 patients (45%) experienced sudden decompensation of chronic heart failure regardless of the underlying cause. The ejection fraction on average was 28.5 ± 8.8%. 13 people passed away while they were hospitalized. P value =0.002 indicates that BNP upon admission was a significant predictor of in-hospital death. Over the next one month, 5 incidents (2 fatalities and 3 re-hospitalizations) happened after release. Both the baseline and discharge BNP values (P values =0.02 and 0.002, respectively) were predictive of the 1-month outcome. Conclusion: BNP concentration is a helpful prognostic indicator that, in confirmed cases with heart failure, predicts death and rehospitalization at 1-month follow-up and aids in the identification of patients who require more extensive medication treatment and continuous follow-up.

Predictors of mortality and cardiovascular outcomes in Emery-Dreifuss muscular dystrophy in a long-term follow-up.

Emery-Dreifuss muscular dystrophy (EDMD) is an extremely rare muscular dystrophy due to either emerinopathy (EMD) or laminopathy (LMNA). The main risk for patients is that of cardiovascular complications. This study aimed to identify predictors of adverse clinical events in patients with EDMD in a long-term follow-up observation. A total of 45 patients with confirmed EMD or LMNA mutation were included in the study. The relationships between clinical parameters, the overall survival rate, and risk factors for disease progression were assessed. The primary endpoint was defined as death, while the secondary endpoint comprised death, resuscitated cardiac arrest (RCA), heart transplant (HTX), stroke, end-stage heart failure (ESHF), and hospitalization due to heart failure (HF). During a median length of follow-up observation of ten years (interquartile range, 5-15), ten patients (22%) died, one suffered RCA, two had HTX, and six suffered ischemic strokes (13%). Seven patients developed ESHF, and eight were hospitalized due to HF. The secondary endpoint occurred in 16 patients (36%). LMNA mutation (hazard ratio [HR], 6.01; 95% confidence interval [CI], 1.61-22.4; P = 0.008) and higher serum N-terminal fragment of B-type natriuretic peptide (NT-proBNP) concentration (HR, 1.29; 95% CI, 1.06-1.56 per 100 pg/ml; P = 0.01) increased the risk of death. Higher tricuspid annular plane systolic excursion (TAPSE) decreased the risk for the secondary endpoint (HR, 0.78; 95% CI, 0.68-0.90 mm; P <0.001). NT-proBNP >257 pg/ml and TAPSE <21 mm may be assumed as the best cut-off values for the primary and secondary endpoints, respectively. LMNA mutation and higher NT-proBNP concentration were associated with increased mortality in EDMD. Lower TAPSE was a predictor of a composite secondary endpoint in EDMD.

Application of B-Type Natriuretic Peptide in Neonatal Diseases.

Numerous congenital or secondary diseases, including, heart disease, respiratory disease, sepsis and many others, can lead to neonatal death. B-type natriuretic peptide (BNP) is a peptide hormone secreted by ventricular cells following an increase in ventricular wall tension. BNP functions to promote vasodilation, diuresis, and sodium release to regulate blood pressure. BNP is a sensitive index reflecting ventricular function, which may aid the diagnosis and monitoring of various neonatal diseases. In neonates, there is currently no consensus on a reference BNP level, as the plasma BNP concentration of healthy newborns varies with age, peaks in the first week after birth, and then gradually decreased to a stable level. In disease states, the correlation between the plasma BNP concentration and the results of echocardiography is good, which is of great significance in the screening, monitoring, and prognosis evaluation of neonatal cardiovascular diseases, including congenital heart disease, patent ductus arteriosus, etcetera. It also facilitates the judgment of the efficacy of treatment and perioperative management. Moreover, the monitoring of plasma BNP concentration provides guidance for the diagnosis, evaluation, and treatment selection of certain neonatal respiratory diseases and neonatal sepsis. This review summarizes the normal BNP values and discusses the application value of BNP in relation to physiological and pathological aspects in neonates.

Abstract 9071: Prognosis of Elderly Non-Valvular Atrial Fibrillation Patients Stratified by B-type Natriuretic Peptide Concentration: A Subanalysis of Data from the ELDERCARE-AF Trial

Introduction: B-type natriuretic peptide (BNP) is a known predictor of prognosis and disease severity in patients with heart failure. However, only limited data are available on the relation between BNP and outcomes in very elderly (age, ≥ 80 years) patients ineligible for standard anticoagulation with non-valvular atrial fibrillation (NVAF). Therefore we evaluated the prognostic and therapeutic outcomes of very elderly Japanese NVAF patients stratified by BNP concentration. Methods: This was a subanalysis of data from ELDERCARE-AF, a multicenter, randomized, double-blind, placebo-controlled phase 3 study of edoxaban 15 mg (once daily) in very elderly Japanese NVAF patients considered ineligible for standard anticoagulant treatment. Patients were stratified according to BNP concentration at enrollment, and their outcomes were compared. The primary efficacy endpoint was stroke or systemic embolism (SSE). The primary safety endpoint was major bleeding. Results: A total of 984 patients (mean age, 86.6 years) were randomized to edoxaban 15mg ( n = 492) or placebo ( n = 492). BNP concentration at enrollment was &lt; 200 pg/mL (low), 200 to &lt; 400 pg/mL (moderate), and ≥ 400 pg/mL (high) in 428, 300, and 256 patients, respectively. Mean CHADS 2 score was 2.9 in the low BNP and 3.2 in the moderate and high BNP groups. The incidences of SSE were 1.2%/patient-year (7/428), 5.9%/patient-year (24/300), and 8.6%/patient-year (28/256) in the low, moderate, and high BNP groups, respectively: unadjusted HR = 5.03 (95% confidential interval [CI], 2.17-11.67), P = 0.0002, for low versus moderate BNP; unadjusted HR = 7.07 (3.09-16.18), P &lt; 0.0001, for low versus high BNP. No significant intergroup differences were found for the incidence of major bleeding. Edoxaban 15mg was superior to placebo in preventing SSE in the moderate and high BNP groups: unadjusted HR, 0.27 (0.10-0.73), P &lt; 0.01, and unadjusted HR, 0.34 (0.15-0.81), P &lt; 0.05, respectively. There was no significant difference in major bleeding between the edoxaban 15mg and placebo groups. Conclusions: In very elderly NVAF patients, BNP concentration was positively related to the incidence of SSE, and edoxaban 15mg had a preventive effect, regardless of BNP concentration.

Abstract 9062: A Rapid and Point-of-Care Device for Real-Time Monitoring of Pulmonary Hypertension Biomarkers

Introduction: Pulmonary hypertension (PH) is a life-threatening condition that remains undetected at an early stage because diagnosis relies heavily on physiological presentations. The gold standard for biomolecular analysis is a blood test, which is invasive and increases the risk of infections, particularly in rural areas. To narrow this gap, we used a low-cost fabrication method to develop a sensor for real-time and bedside monitoring of a PH biomarker, B-type natriuretic peptide (BNP) in serum. Hypothesis: The sensor will facilitate research on early identification of the risk of PH from dynamic measurements of biomarkers, which will reduce cardiac failures resulting from delayed and missed diagnoses of PH Methods: We used a low-cost screen-printing technique to fabricate a 3 electrode-based electrochemical sensor on a flexible polyimide substrate (Fig. 1a). The working electrode (WE) was functionalized with anti-BNP. The sensor was interfaced with a potentiostat that applied a potential between the WE and reference electrode (RE) and measured the resulting current from the WE to counter electrode (CE). The BNP/anti-BNP binding on the WE resulted in variations in the redox current. Results: The sensor detected BNP in only 50 μl of fetal bovine serum. Fig. 1b shows the current vs. potential scan for BNP concentrations ranging from 0.1 to 500 pg/mL. The amount of current flow between WE and CE was proportional to the serum BNP levels. The sensor exhibited a sensitivity of 0.584 μA (pg/mL) -1 cm 2 (from Fig. 1c) and a response time of 4s. The sensor also showed high selectivity against common interfering species (Fig. 1d) and good repeatability with a response variability of &lt;1% between identical sensors (Fig. 1e). Conclusions: The project will advance the field of bedside monitoring of PH biomarkers. The low-cost and plug-and-play feature of the sensor allows adoption by rural communities. The sensor can be readily reconfigured and expanded to monitor other biomarkers.

Prognostic value of self-reported subjective exercise capacity in patients with acute dyspnea

Abstract Background Quantitative assessment of self-reported exercise capacity as provided by the Duke Activity Status Index (DASI) is a validated measure of exercise capacity in stable ambulatory patients. Objectives This study aimedto test whether the quantification of self-reported exercise capacityusing the DASI may aid physicians in the risk stratification of patients presenting with acute dyspnea to the emergency department (ED). Methods Basics in Acute Shortness of Breath EvaLuation (BASEL V) was a prospective cohort study recruiting dyspneic patients at the ED. The prognostic value and accuracy of theDASI assessed shortly after presentation were quantified using Cox regression analyses and the Area under the curve (AUC). Results Among 1019 patients eligible for this analysis 529 (51.9%) had an adjudicated final diagnosis of acute heart failure, 75 (7.4%) and 297 (29.1%) patients died within 90 and 720 days after presentation. Unadjusted hazard ratios (HR) and multivariable adjusted hazard ratios (aHR) for 90-day and 720-day mortality increased continuously from the fourth (best self-reported exercise capacity) to the first DASI-quartile (worst self-reported exercise capacity). For 720-day mortality in the first quartile theHR was 9.1 (95%-CI 5.5–14.9) (aHR 6.1 [95%-CI 3.7–10.1]), in the second quartile 6.4 (95%-CI 3.9–10.6) (aHR 4.4 [95%-CI 2.6–7.3]), while in the third quartile the HR was 3.2 (95%-CI 1.9–5.5) (aHR 2.4 [95%-CI 1.4–4.0]). The prognostic accuracy of the DASI was moderate-to-high and higher than that of B-type natriuretic peptide (BNP) and NT-proBNP (N-terminal pro-BNP) concentrations, e.g. for 720-day mortality prediction AUC 0.70 versus 0.64, p=0.020; 0.72 versus 0.68, p=0.074. Conclusions Quantification of self-reported subjective exercise capacityusing the DASI provides moderate-to-high prognostic accuracy in patients presenting with acute dyspnea to the ED and may aid physicians in further risk stratification. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union, the Swiss National Science Foundation. Duke Activity Status Index

Sex Differences in Time-Dependent Changes in B-Type Natriuretic Peptide in Hypertrophic Cardiomyopathy.

Background: Female sex is reported to be associated with poor prognosis in hypertrophic cardiomyopathy (HCM). The plasma B-type natriuretic peptide (BNP) concentration is a prognostic predictor in HCM. However, the effect of sex on BNP concentrations remains unclear among HCM patients.Methods and Results: Patient records in the Clinical Personal Records of HCM national database of the Japanese Ministry of Health, Labour and Welfare from 2009 to 2014 were analyzed. Of 3,570 HCM patients, 611 in whom BNP concentrations were assessed at both baseline and the 2-year follow-up were included in this analysis. The mean age was 60.4 years and 254 (41.6%) patients were female. Median (interquartile range) BNP concentrations were higher in females than males at both baseline (320.3 [159.0–583.1] vs. 182.8 [86.1–363.9] pg/mL; P<0.001) and the 2-year follow-up (299.2 [147.0–535.3] vs. 161.0 [76.2–310.0] pg/mL; P<0.001). Female sex was associated with higher natural log-transformed BNP at the 2-year follow-up regardless of clinical characteristics, including echocardiographic findings and BNP concentrations at baseline (coefficient 0.31; 95% confidence interval 0.13–0.48; P<0.001). Cubic spline analysis showed that, among patients with high BNP concentrations at baseline, females had higher BNP concentrations at the 2-year follow-up than males.Conclusions: In HCM, female sex was associated with higher BNP concentrations than male sex, independent of clinical characteristics, including BNP concentrations at baseline.

Initial Real-World Practical Experience of Sacubitril/Valsartan Treatment in Japanese Patients With Chronic Heart Failure.

Background: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, has demonstrated survival benefit and reduces heart failure hospitalization compared with enalapril in patients with heart failure and reduced ejection fraction. However, its efficacy in real-world practice in Japan remains unknown.Methods and Results: We initiated sacubitril/valsartan treatment for 37 patients (median age 68 years; median left ventricular ejection fraction 37%) between August and November 2020. Within 3 months, sacubitril/valsartan was discontinued in 3 patients due to symptomatic hypotension or worsening heart failure. Two patients were hospitalized due to worsening heart failure, with one of these patients undergoing percutaneous mitral valve repair. Three patients received scheduled non-pharmacological treatment: 1 received cardiac resynchronization therapy (CRT), 1 received CRT and underwent transcatheter aortic valve implantation, and 1 underwent left ventricular assist device implantation. Of the 30 patients who continued sacubitril/valsartan for 3–6 months without additional non-pharmacological therapy, there was a tendency for a decrease in N-terminal pro B-type natriuretic peptide concentrations (baseline vs. after 3–6 months ARNI treatment; median 733 vs. 596 pg/mL; P=0.097) and an increase in left ventricular ejection fraction (median 37% vs. 39%; P=0097).Conclusions: Sacubitril/valsartan therapy with a lower initial dose was safe and may be effective in Japanese heart failure patients in a real-world setting. Further evaluation of optimal patient selection and clinical management using sacubitril/valsartan is warranted.