Elevated B-type Natriuretic Peptide Research Articles

Use of the Clinical Examination in the Diagnosis of Cardiac Syncope.

Patient history: Age at first syncopal episode older than 35 years = 3.3 History of atrial fibrillation or flutter = 7.3 Known severe structural heart disease = 3.3 to 4.8 Dyspnea prior to syncope = 3.5 Chest pain/angina prior to syncope = 3.4 to 3.8 Cyanotic during syncope = 6.2 Diagnostic tests: High-sensitivity cardiac troponin T > 42 pg/mL = 5.1 High-sensitivity cardiac troponin I > 31.3 pg/mL = 5.4 NT-proBNP ≥ 210.5 pg/mL = 47 NT-proBNP > 1966 pg/mL = 5.8 BNP > 302 pg/mL = 6.3 Multivariable evaluation: Heart disease, abnormal ECG, or both = 2.3 EGSYS score 3 or more = 2.8 to 3.3 Vasovagal score less than −2 = 1.7 to 8.6 Patient history: Age at first syncopal episode 35 years or younger = 0.13 Diagnostic tests: Normal cardiac troponin T or I = 0.15 to 0.39 Normal BNP level = 0.16 to 0.21 Multivariable evaluation: EGSYS score less than 3 = 0.12–0.17 Absence of heart disease, abnormal ECG or both = 0.20 Vasovagal score −2 or more = 0.10–0.84 Syncope or transient loss of consciousness is a common problem seen in the emergency department (ED), accounting for 1% to 1.5% of ED visits annually.1 Cardiac syncope caused by cerebral hypoperfusion secondary to cardiopulmonary events such as arrhythmia or structural heart disease, accounts for 5% to 21% of syncope events.2 Cardiac syncope is associated with an increased risk of premature death and cardiac events.3, 4 It is therefore important for emergency providers to differentiate cardiac syncope from other causes. This systematic review by Albassam et al.5 evaluated patient characteristics, physical examination findings, and diagnostic tests to identify cardiac causes of syncope. The authors searched the MEDLINE, Embase, CINAHL, and Cochrane databases, selecting 11 studies that met inclusion and exclusion criteria. Each study included at least 10 subjects aged 12 years or older, for a total of 4,317 patients. Studies were assigned levels of evidence developed for the Rational Clinical Examination series.6 Several historical factors were associated with an increased likelihood of cardiac syncope including age at first syncopal episode 35 years or older; history of atrial fibrillation or flutter; known severe structural heart disease; dyspnea or chest pain prior to syncope; and witnessed cyanosis during syncope. An elevated cardiac troponin T or I and an elevated B-type natriuretic peptide (BNP) both modestly increased the probability of cardiac syncope. Factors that decreased the probability included age less than 35 years at first syncopal episode; normal cardiac troponin T or I; and normal BNP. Combinations of findings such as Evaluation of Guidelines in Syncope Study (EGSYS) score ≥ 3; vasovagal score < −2; and abnormal electrocardiogram, heart disease, or both were more useful when absent than when present. The results of this review should be interpreted cautiously. Included studies generally defined cardiac syncope based on cardiologist judgment. Five of 11 studies included specialty referral populations or inpatients, leading to the potential for spectrum bias. Applying these results to a general ED population might lead to additional testing or interventions in patients who have lower risk of cardiac syncope than the studied population. Misclassification may have further skewed the results as patients with unexplained syncope were excluded from several studies. Many of the clinical findings resulted from single studies. Studies often included a wide age range of patients despite the incidence of syncope, related ED visits, and serious outcomes increasing sharply after the age of 60.7 Cardiac biomarkers such as troponin or BNP testing appear to be an attractive diagnostic option, however, they did not rule in or rule out cardiac syncope. Moreover, these cardiac biomarkers were likely used to diagnose cardiac syncope leading to incorporation bias. ACEP clinical policy, appreciating these limitations, suggests a risk stratification approach focusing on patient history and physical examination to avoid unnecessary testing and hospital admissions.1 In summary, the accurate diagnosis of cardiac syncope is helpful in determining an appropriate plan of care. While no single variable can independently diagnose or exclude cardiac syncope, several clinical findings may be used cohesively to help guide health care providers.

Risk Stratification of Older Adults Who Present to the Emergency Department With Syncope: The FAINT Score

Older adults with syncope are commonly treated in the emergency department (ED). We seek to derive a novel risk-stratification tool to predict 30-day serious cardiac outcomes. We performed a prospective, observational study of older adults (≥60 years) with unexplained syncope or near syncope who presented to 11 EDs in the United States. Patients with a serious diagnosis identified in the ED were excluded. We collected clinical and laboratory data on all patients. Our primary outcome was 30-day all-cause mortality or serious cardiac outcome. We enrolled 3,177 older adults with unexplained syncope or near syncope between April 2013 and September 2016. Mean age was 73 years (SD 9.0 years). The incidence of the primary outcome was 5.7% (95% confidence interval [CI] 4.9% to 6.5%). Using Bayesian logistic regression, we derived the FAINT score: history of heart failure, history of cardiac arrhythmia, initial abnormal ECG result, elevated pro B-type natriuretic peptide, and elevated high-sensitivity troponin T. A FAINT score of 0 versus greater than or equal to 1 had sensitivity of 96.7% (95% CI 92.9% to 98.8%) and specificity 22.2% (95% CI 20.7% to 23.8%), respectively. The FAINT score tended to be more accurate than unstructured physician judgment: area under the curve 0.704 (95% CI 0.669 to 0.739) versus 0.630 (95% CI 0.589 to 0.670). Among older adults with syncope or near syncope of potential cardiac cause, a FAINT score of zero had a reasonably high sensitivity for excluding death and serious cardiac outcomes at 30 days. If externally validated, this tool could improve resource use for this common condition.

Alteration of Cardiac Performance and Serum B-Type Natriuretic Peptide Level in Healthy Aging

BackgroundThe impact of aging on cardiac function is not fully elucidated. Speckle-tracking echocardiography can unmask subclinical cardiac dysfunction. ObjectivesThis study investigated the impact of healthy aging on left ventricular (LV), right ventricular (RV), and left atrial (LA) performance and their relationship with serum B-type natriuretic peptide (BNP) levels in a sample of the general population without prevalent cardiovascular risk factors and structural heart disease. MethodsSpeckle-tracking echocardiography was performed to assess LV global longitudinal strain (LVGLS), RV free wall strain, and LA phasic strain in 481 normal weight healthy participants who underwent extensive cardiovascular examination. Elevated BNP was defined as BNP >37.82 pg/ml for men and >50.86 pg/ml for women, which was the 90th percentile of BNP value distribution in the study population. ResultsMean age was 60 ± 12 years (range: 24 to 86 years), and 46% of the participants were men. The earliest alteration of age-related cardiac performance was observed in LA reservoir and conduit strain starting from decade 5, followed by elevated E/e′ from decade 6. LVGLS decreased starting from decade 7, whereas there were no significant differences in RV strain, LV ejection fraction, or LV mass index across the decades. In the multivariable linear regression analyses, age was an independent predictor of decreased LVGLS (standardized β = 0.21; p < 0.001) and decreased LA phasic strain (standardized β = −0.40 and −0.61 for reservoir and conduit strain; both p < 0.001). Age and LA strain were significantly associated with elevated BNP values (adjusted odds ratios: 1.10 and 0.93; both p < 0.05, respectively), independent of ventricular morphology and function. ConclusionsDecreases in LA reservoir and conduit strain are the earliest markers of age-related cardiac remodeling, and LA reservoir strain is an independent predictor of elevated serum BNP level, with both possibly being markers of increased risk of heart failure in older adults.

Differential Regulation of ANP and BNP in Acute Decompensated Heart Failure: Deficiency of ANP

ObjectivesThis study investigated the differential regulation of circulating atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in patients with acute decompensated heart failure (ADHF) and tested the hypothesis that a relative deficiency of ANP exists in a subgroup of patients with ADHF. BackgroundThe endocrine heart releases the cardiac hormones ANP and BNP, which play a key role in cardiovascular (CV), renal, and metabolic homeostasis. In heart failure (HF), both plasma ANP and BNP are increased as a compensatory homeostatic response to myocardial overload. MethodsANP and BNP concentrations were measured in a small group of patients with ADHF (n = 112). To support this study’s goal, a total of 129 healthy subjects were prospectively recruited to establish contemporary normal values for ANP and BNP. Plasma 3′,5′cyclic guanosine monophosphate (cGMP), ejection fraction (EF), and body mass index (BMI) were measured in these subjects. ResultsIn cases of ADHF, 74% of patients showed elevated ANP and BNP. Importantly, 26% of patients were characterized as having normal ANP (21% of this subgroup had normal ANP and elevated BNP). Cyclic GMP was lowest in the ADHF group with normal levels of ANP (p < 0.001), whereas BMI and EF were inversely related to ANP levels (p = 0.003). ConclusionsAmong a subgroup of patients hospitalized with ADHF, the presence of an ANP deficiency is consistent with a differential regulation of ANP and BNP and suggests the existence of a potentially compromised compensatory cardiac endocrine response. These findings have implications for the pathophysiology, diagnostics, and therapeutics of human HF.

Post-procedural tricuspid regurgitation predicts long-term survival in patients undergoing percutaneous mitral valve repair

BackgroundFunctional tricuspid regurgitation (TR) is frequently present in patients with severe mitral regurgitation and is associated with worse outcome. While percutaneous mitral valve repair (PMVR) is on the increase, the role of TR in those patients is unclear. This study aimed to compare pre- and post-procedural TR and investigated the impact of post-procedural TR and major clinical risk factors on long-term survival in patients undergoing PMVR. MethodsIn this retrospective observational cohort study, data from 213 consecutive patients at a tertiary care center undergoing PMVR from 2010 to 2016 were analyzed. Two different groups, dichotomized according to the degree of TR (none/mild and moderate/severe) were compared. Multivariable analyses were performed assessing predictors for long-term survival adjusting for major risk factors. ResultsFollowing PMVR TR was significantly reduced by at least 1 grade in 23.0% (p=0.001), while echocardiographic pulmonary pressure was decreased (TR Vmax 3.21±0.49m/s vs. 2.98±0.53m/s; p=<0.001). Patients with moderate or severe TR presented with worse New York Heart Association functional class and elevated N-terminal pro B-type natriuretic peptide levels compared to patients with none or mild TR. Median survival time was 1458 days. Proportional hazards model, adjusted for major risk factors, revealed post-procedural TR grade (HR 2.055, CI 1.317–3.206, p=0.02), severely impaired left ventricular function (HR 3.145, CI 1.199–8.250, p=0.020), and chronic kidney disease [glomerular filtration rate (GFR) 30–60ml/min HR 1.917, CI 1.109–3.314, p=0.020; GFR<30ml/min HR 3.969, CI 1.981–7.951, p<0.001] as independent predictors for long-term survival. ConclusionPost-procedural moderate and severe TR predicts worsened long-term survival in patients undergoing PMVR and is associated with adverse clinical outcome. Whether outcome might be improved by interventional reduction of post-procedural TR has to be investigated in the future.

BNP Levels as a Predictive Marker for Preterm Birth in Women With Hypertensive Disorders in Pregnancy [10A

INTRODUCTION: Few tests are able to determine the risk of preterm birth (PTB) in women with hypertensive disorders in pregnancy. B-type natriuretic peptide (BNP) is a sensitive marker discerning early cardiac dysfunction and volume expansion in these women. The primary purpose of this study is to evaluate BNP levels in pregnant women with hypertensive disorders as a predictor of medically indicated PTB. METHODS: Pregnant women who presented at Touro Infirmary, New Orleans, LA, between April 2015 and May 2017 for hypertension evaluation were eligible for enrollment. BNP values were collected prior to and at delivery. A BNP level of >100 was considered elevated. All obstetrical and neonatal outcomes were recorded. Fisher's test was used to compare the proportion of patients with elevated BNP levels for women with versus without indicated PTB and for women with versus without newborn requiring neonatal intensive care unit (NICU) stay. Neonatal weight and Apgar scores were compared using the Wilcoxon rank sum test. RESULTS: Of 52 women with hypertensive disorders as an indication for PTB, 34.6% had an elevated BNP, as compared to 12.5% of those with hypertensive disorders that delivered at term (p=0.004). Of 41 women whose newborn required NICU stay, 34.2% had an elevated BNP, as compared to 15.4% of those whose newborn did not require NICU stay (p=0.021). Neonatal weight and Apgar scores were not different (p>0.05) for those with elevated maternal BNP levels. CONCLUSION: BNP measurement may be helpful in determining which women with hypertensive disorders are at higher risk for medically indicated PTB.

B-Type Natriuretic Peptide (BNP) and Hypertensive Disorders in Pregnancy [31H

INTRODUCTION: B type natriuretic peptide (BNP) is a sensitive marker discerning early cardiac dysfunction and has demonstrated correlation with volume expansion and pressure overload in hypertensive disorders in pregnancy. The purpose of this study is to examine variations of BNP values in women with chronic hypertension and severe preeclampsia as indications for delivery. METHODS: Pregnant women greater than 20 weeks gestation and women up to 14 days postpartum presenting at Touro Infirmary in New Orleans between April 1, 2015 and May 30, 2017 for hypertension evaluation were eligible for inclusion. After informed consent, BNP values were collected at any evaluation for hypertension during the antepartum period, at admission for delivery and up to 14 days postpartum. 132 women were included. A BNP value above 100 pg/dL was considered elevated. Standards for hypertension and preeclampsia were determined by criteria described by the American College of Obstetrics and Gynecology. RESULTS: Of 18 women with chronic hypertension exacerbation as an indication for delivery, none had an elevated BNP, as compared to 24.6% of women without the indication (n =132, p=0.0248). Of 43 women with severe preeclampsia as an indication for delivery, 37.2% had an elevated BNP, as compared to 13.5% of women without the indication (p=0.003). CONCLUSION: Women with chronic hypertension exacerbation as an indication for delivery are not likely to have elevated BNP. Women with severe preeclampsia as an indication for delivery are more likely to have elevated BNP, which is congruent with the notion that BNP is a measure of acute stress to the heart.

Frailty index is associated with increased risk of elevated BNP in an elderly population: the Rugao Longevity and Ageing Study.

To explore whether frailty, defined by frailty index (FI), is associated with the risk of elevated B-type natriuretic peptide (BNP), a surrogate endpoint of cardiovascular events. Data of 1382 community-dwelling elders who had no documented cardiovascular diseases aged 70-84years from the ageing arm of the Rugao Longevity and Ageing Study was used. Traditional risk factor index (TI) was constructed using eight established cardiovascular-related risk factors. FI was constructed using 36 health deficits. Elevated BNP was defined as BNP ≥ 100pg/mL. Cardiovascular events include incident major cardiovascular events and cardiovascular death. During a 3-year follow-up period, 97 participants had cardiovascular events. TI was not associated with the risk of elevated BNP, but was associated with cardiovascular events (HR = 1.16, 95% CI 1.01-1.34). Frailty index was not only associated with cardiovascular events (HR = 1.32, 95% CI 1.06-1.64), but also associated with elevated BNP with an OR of 1.22 (95% CI 1.02-1.47) for each 0.1 increment. Further, both frailty (OR = 1.93, 95% CI 1.67-3.17) and pre-frailty (OR = 1.54, 95% CI 1.06-2.25) were associated with increased risk of elevated BNP. FI is associated with increased risks of both cardiovascular events and surrogated endpoint of cardiovascular disease-elevated BNP. Frailty may be a non-traditional risk factor of cardiovascular diseases and frailty index may be a measurement for early identifying high risk elderly individuals of cardiovascular abnormities.

Annals for Educators - 15 January 2019.

Annals for Educators - 15 January 2019.

Predictive values of dyslipidemia and B-type natriuretic peptide levels in juvenile systemic lupus erythematosus: A two center-experience.

B-type natriuretic peptide (BNP) is a biomarker that helps in determining the diagnosis and prognosis of heart failure (HF). There is an increased risk for cardiovascular disease (CVD) in systemic lupus erythematosus (SLE) with high disease activity, demonstrated by the higher frequency of dyslipidemia and higher BNP concentrations than in healthy controls. The aim of the work was to evaluate the association between the levels of lipids and BNP in pediatric patients with SLE with HF. We classified our subjects into three groups as follows: Group 1 (active SLE group): included 38 patients who subgrouped into 16 with HF and 22 without HF; Group 2 (inactive SLE group): included 38 patients, and Group 3 (control group): included 38 apparently healthy children. All children were subjected to complete history taking, clinical examination, SLE disease activity index scoring and investigations included complete blood count, erythrocyte sedimentation rate, 24-h urinary protein, anti-double strand deoxy-ribonucleic acid and anti-nuclear antibody, lipid profile, serum albumin, protein, and BNP. There was a significantly elevated lipid level and decreased high-density lipoproteins in lupus patients than in healthy controls. The dyslipidemia was more prevalent in active SLE. There were significantly elevated BNP levels in lupus patients than in healthy controls. In this study, we found that BNP was a biomarker in determining the diagnosis and prognosis of HF. This study revealed that BNP levels were increased in SLE patients without cardiac symptoms as compared to healthy controls; furthermore, the BNP levels were higher in active SLE patients with HF. The data indicated that there is a high risk for CVD in SLE with high disease activity, as demonstrated by the higher frequency of dyslipidemia and higher BNP concentrations than in healthy controls.

B-type natriuretic peptide is associated with remodeling and exercise capacity after transcatheter aortic valve replacement for aortic stenosis.

BackgroundWe aimed to assess longitudinal changes of B‐type natriuretic peptide (BNP) in aortic stenosis (AS) patients treated by transcatheter aortic valve replacement (TAVR).MethodsFrom our TAVR database, we identified 193 consecutive patients with severe symptomatic AS who underwent TAVR and were prospectively followed using serial BNP levels and echocardiography. Patients were divided into subgroups according to type of left ventricular (LV) remodeling as having normal LV mass and relative wall thickness, or showing concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH).ResultsAt baseline, 30 patients (16%) had EH, 115 (60%) had CH, 37 (19%) had CR, and 11 (6%) had normal LV geometry. After TAVR, BNP decreased in the first 30 days, with further improvement during follow‐up. Patients with EH had higher BNP at baseline (P < 0.01) and a greater subsequent decrease (P < 0.001). During the median follow‐up of 1331 days (interquartile range: 632‐1678), 119 (62%) patients died. BNP showed a time‐dependent association with all‐cause mortality both in a univariable (hazards ratio [HR] 1.24, 95% confidence interval [CI]: 1.04‐1.47, P = 0.017), and in a multivariable model with Society of Thoracic Surgeons score and baseline BNP forced into the analysis (HR 1.32, 95% CI: 1.001‐1.73, P = 0.049). Elevated BNP was associated with a larger LV end‐diastolic volume index (P < 0.001) and shorter 6‐minute walk test distance (P = 0.013) throughout follow‐up.ConclusionIn patients with AS, BNP was associated with LV remodeling phenotypes and functional status before and after TAVR. Elevated BNP levels were associated with poor prognosis.

Characterization of Cardiovascular Adverse Events and B-Type Natriuretic Peptide Levels in Patients with Multiple Myeloma Who Are Treated with Carfilzomib

BackgroundCarfilzomib (K), a second generation proteasome inhibitor that is approved for patients (pts) with relapsed refractory multiple myeloma (RRMM) is associated with increased cardiovascular (CV) adverse effects (AE), in particular hypertension (HTN), dyspnea and cardiac failure (CCF), based on the ENDEAVOR (Dimopoulos, MA. et al. Lancet 2016) and ASPIRE studies (Stewart, K.et al. NEJM 2015). The clinical characteristic and underlying mechanism of K induced CVAE have been poorly elucidated, and the limited published data on the utility of cardiac enzymes as biomarkers have not been revealing. We conducted a retrospective single centre review of K-treated pts who have undergone systemic serial cardiovascular and cardiac enzyme assessment, to profile the nature of CVAE and patterns in cardiac enzymes that might have predictive utility in K-induced CVAE.Method:Between January 2016 to June 2018, all pts who were treated with K (D1,2,8,9,15,16 in a 28 day cycle)-based regimen for RRMM at St.Vincent's Hospital Melbourne underwent systematic cardiovascular assessment including documentation of baseline cardiac risk factors (RF) and transthoracic echo (TTE). Serial troponin, creatinine kinase (CK) and B-type Natriuretic Peptide (BNP) were performed at baseline (C1D1 or 2), mid cycle (D8 or 9) and end of treatment (D16) of every cycle. Repeat TTE was done at physicians' discretion. Systematic documentations of CVAEs (graded according to CTCAEv5) were retrieved from medical records. The incidence and severity of CVAE was collated and correlated with serial cardiac enzyme levels, the association of which was tested using Student's t-test.Results76 pts (67% male; median age 66(46-86) years) with RRMM who received a median of 6 cycles (1-26) of K-based treatment were included in this analysis. At baseline, 16 pts (21%) had at least 1 CVRF including HTN, history of ischaemic heart disease, hyperlipidaemia, diabetes or smoking. The incidence of HTN prior to treatment was 39%. On treatment, the incidence of HTN was 85% (28% grade≥3). 17% of pts required the addition of antihypertensive medications and 11% had K dose reduction due to HTN. K-related dyspnea occurred in 53% of pts (28% grade≥3), 52% of who required K dose reduction/interruption. CCF occurred in 14.5% (grade≥3, 13%) that all necessitated K interruption/dose reduction. 69 pts had baseline TTE that showed a median RVSP (right ventricular systolic pressure) of 32mmHg (range 20-48). On treatment, 38 pts had repeat TTE, mainly driven by dyspnea with a median RVSP of 41(20-93mmHg). Of the 18 pts with grade≥3 dyspnea who had repeat TTE, 83% had RSVP ≥39mmHg and 33% had RVSP≥50mmHg, compared to 70% with RSVP ≥39mmHg and 10% RVSP≥50mmHg in the group with grade 1-2 dyspnea. Troponin_I and CK level did not change significantly throughout K-treatment. However BNP level rose and fell within each cycle, typically with peaks at mid cycle (D9 and D16) and troughs at the beginning of a new cycle (D1 or 2). 87.1% of pts had at least one elevated BNP (>100ng/L) with a median maximal level of 300ng/L (range 114-2320ng/L). There was a significant difference in the incidence of grade ≥3 CVAEs (mainly HTN) in pts whose mid cycle BNPs (D9 or 16) were elevated in ≥50% of measurements during the first 4 cycles of K compared to the rest (65.5% vs. 25.0%, p=0.0084). In pts with dyspnea, persistent rise in mid cycle BNPs that does not normalise prior to next treatment cycle trended towards an increased incidence of raised RVSP of ≥39mmHg (21.7% vs. 7.9%, p=0.0543).Conclusion.The incidence of CVAEs in pts treated with K is higher in the real-world setting compared to that reported in the Endeavor and ASPIRE studies. Dyspnea is frequent, the degree of which correlates with the degree of raised RVSP, thus indicating pulmonary hypertension as a contributor to dyspnea in the setting of K treatment. BNP level typically peaks during mid cycle and troughs at the beginning of next cycle, indicating a temporal relationship to K infusions. In pts with dyspnea, the association of persistent rise in mid-cycle BNP (rather than troponin or CK) with raised RVSP and HTN perhaps indicate transient endothelial dysfunction as the mechanism for K-induced CVAE rather than myocyte injury. DisclosuresQuach:Amgen: Consultancy, Research Funding; Sanofi Genzyme: Research Funding; Janssen Cilag: Consultancy; Celgene: Consultancy, Research Funding. Tam:Roche: Honoraria; AbbVie: Honoraria, Research Funding; Pharmacyclics: Honoraria, Travel funding; Beigene: Honoraria, Other: Travel funding; Pharmacyclics: Honoraria; Gilead: Honoraria; Janssen: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Beigene: Honoraria, Other: Travel funding; Gilead: Honoraria; Roche: Honoraria.

Abstract 16779: Mitochondrial Related Intragraft Gene Expression During Acute Rejection After Heart Transplantation

Introduction: Endomyocardial biopsies (EMB) for the surveillance of acute cellular rejection (ACR) after heart transplant (HT) is inconsistent and provides limited information. Mitochondrial dysfunction is associated with poor allograft prognosis and can overstimulate the inflammatory response. Mitochondrial related gene expression (GE) in EMB may be useful as a functional surrogate for EMB. Hypothesis: We hypothesize that down-regulated mitochondrial associated GE in EMB correlates with ACR. Methods: We collected 64 EMB from 47 post HT patients (mean age 50 ± 14.7 years). Purified mRNA was subjected to whole-genome next-generation sequencing. Weighted gene co-expression network analysis was applied to construct functional gene modules. Module derived eigengenes were correlated with ISHLT EMB criteria or using an unsupervised classification method we previously developed and B-type natriuretic peptide (BNP) levels. Biological significance and function of each module were assessed by gene ontology (GO) and pathway analyses. Highly relevant genes were identified by Hub gene analysis. Results: The reconstructed network resulted in 16 modules including two mitochondria-related modules (MRM) and one immune response module (IRM). Compared to 0R (n= 30/46.9%) samples, 2R (n= 11/17.2%) EMB showed enrichment of IRM and decreased expression of MRM. ISHLT 1R (n= 23/35.9%) samples did not show a significant correlation with IRM or MRM. Following the unsupervised classification method, findings were concordant, with higher phenotype-module eigengene correlation and significance level. MRM Hub genes included ATP5B, ATP5O, ACO2, COX14, COX4I1 , FH, NDUFV1, PDK2, SDHA and UQCR11 among others. GO categories enriched by these genes included oxidative phosphorylation, beta-oxidation, tricarboxylic acid cycle, glycolysis and gluconeogenesis. There was an inverse correlation between MRM and BNP level and positive correlation between IRM and BNP (Figure). Conclusions: EMB of patients with ISHLT 2R ACR show decrease activity of MRM, increased activity of IRM and elevated BNP suggesting an inverse functional relationship between immune activation, mitochondrial activity and cardiac allograft function.

Association of BNP with Frailty in Elderly Population: Rugao Longevity and Ageing Study

To explore the associations of B-type natriuretic peptide (BNP) with physical frailty status as well as each domain of frailty in a general elderly population. Cross-sectional analysis of prospective cohort study. All of 31 communities in Jiang'an township. Overall 1338 participants (aged 70-89 years, mean 77.42±4.08 years) without a history of cardiovascular diseases in the third-wave of the aging arm of the Rugao Longevity and Aging Study (RuLAS). Frailty was defined as the presence of ≥3 domains among five modified Fried's criteria (unintentional weight loss, low physical activity level, weakness (low grip strength), exhaustion, and slowness (slow gait speed)) and pre-frailty as the presence of 1-2 domains. The prevalence of frailty and pre-frailty was 10.4% and 53.3%, respectively, in this elderly population. Elevated BNP (≥100 pg/mL) was significantly associated with pre-frailty (OR: 1.61, 95% CI: 1.13-2.29) and frailty (OR: 2.63, 95% CI: 1.61-4.32) after adjustment for covariates. In addition, elevated BNP was associated with low grip strength (OR: 2.00, 95% CI: 1.41-2.82) and low gait speed (OR: 1.62, 95% CI: 1.15-2.28) after adjustment for multiple covariates. Log BNP was inversely associated with grip strength (r= -0.265, p<0.001) and gait speed (r= -0.189, p<0.001). Elevated plasma BNP was associated with increased risks of frailty, pre-frailty, and low levels of grip strength and gait speed in the elderly community people.

Echo- and B-Type Natriuretic Peptide-Guided Follow-Up versus Symptom-Guided Follow-Up: Comparison of the Outcome in Ambulatory Heart Failure Patients.

Recent European Society of Cardiology and American Heart Association/American College of Cardiology Guidelines did not recommend biomarker-guided therapy in the management of heart failure (HF) patients. Combination of echo- and B-type natriuretic peptide (BNP) may be an alternative approach in guiding ambulatory HF management. Our aim was to determine whether a therapy guided by echo markers of left ventricular filling pressure (LVFP), lung ultrasound (LUS) assessment of B-lines, and BNP improves outcomes of HF patients. Consecutive outpatients with LV ejection fraction (EF) ≤ 50% have been prospectively enrolled. In Group I (n=224), follow-up was guided by echo and BNP with the goal of achieving E-wave deceleration time (EDT) ≥ 150 ms, tissue Doppler index E/e′ < 13, B-line numbers < 15, and BNP ≤ 125 pg/ml or decrease >30%; in Group II (n=293), follow-up was clinically guided, while the remaining 277 patients (Group III) did not receive any dedicated follow-up. At 60 months, survival was 88% in Group I compared to 75% in Group II and 54% in Group III (χ2 53.5; p < 0.0001). Survival curves exhibited statistically significant differences using Mantel–Cox analysis. The number needed to treat to spare one death was 7.9 (Group I versus Group II) and 3.8 (Group I versus Group III). At multivariate Cox regression analyses, major predictors of all-cause mortality were follow-up E/e′ (HR: 1.05; p=0.0038) and BNP >125 pg/ml or decrease ≤30% (HR: 4.90; p=0.0054), while BNP > 125 pg/ml or decrease ≤30% and B-line numbers ≥15 were associated with the combined end point of death and HF hospitalization. Evidence-based HF treatment guided by serum biomarkers and ultrasound with the goal of reducing elevated BNP and LVFP, and resolving pulmonary congestion was associated with better clinical outcomes and can be valuable in guiding ambulatory HF management.

Clinical Utility of B-Type Natriuretic Peptide on Pediatric Intensive Care Unit Admission in Predicting Mechanical Ventilatory/Circulatory Support for Heart Failure

Background: Increased B-type natriuretic peptide (BNP) level is known as a predictive value for cardiac dysfunction in intensive care unit (ICU) patients. Objectives: To verify the association between BNP on admission and clinical outcomes including need for mechanical ventilatory/circulatory support and mortality in patients with heart failure (HF) in pediatric intensive care unit (PICU). Methods: Medical records of 132 HF patients admitted to PICU between February 2009 and August 2015 were reviewed for demographic, clinical, and laboratory data. Results: Among 113 patients who were finally included, mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO) were used in 64 (56.6%) and 19 (16.8%) patients, respectively. Parameters associated with MV were high pediatric risk of mortality (PRISM) III score; highest vasoactive-inotropic score within 24 h of admission; elevated lactic acid, BNP, CK-MB, and troponin I levels. Parameters associated with ECMO were high PRISM III score, reduced left ventricular ejection fraction (LVEF), and elevated lactic acid and BNP levels. Only high PRISM III score and BNP were associated with mortality. The sensitivity and specificity of BNP with a cutoff value of 1848 pg/mL were 75.4% and 72.7% for MV and 89.5% and 50.0% for ECMO. Conclusions: In ICU settings, BNP levels on admission may be useful biomarkers during critical decision making including the determination of mechanical ventilatory/circulatory support.

Assessment of Soluble ST2 and BNP in Pediatric Patients with Left Ventricular Dysfunction

Objective We sought to determine whether soluble suppression of tumorigenicity (ST2) and B-type natriuretic peptide (BNP) are elevated in children with left ventricular dysfunction (LVD). Background Novel biomarkers could be of prognostic value in the management of LVD. METHODS: Data were analyzed from non-hospitalized patients diagnosed with chronic LVD (ejection fraction [EF] 3 months since diagnosis) at Cincinnati Children's Hospital between 2013 and 2016. We excluded neuromuscular disorders, chronic kidney and lung disease, and patients with LVD with malignancy involved. Measurement of biomarkers, heart failure functional status assessment, and non-invasive imaging assessment of ventricular function was performed. Results A total of 92 patients were included, with median age 17 years [IQR 9.5 - 20 years], 43.5% female, and 76.1% Caucasian. Soluble ST2 was elevated in children with LVD compared with controls (median 25.7 ng/mL [IQR 18.8 - 35 ng/mL] versus median 21 ng/mL [IQR 16 to 29 ng/mL]; P 100 ng/mL compared to those below that threshold (P Conclusion Soluble ST2 and BNP are higher in pediatric patients with LVD indicating hemodynamic stress. While there was no relationship between functional status and the biomarkers studied, those patients with elevated BNP did have a lower median EF. Future study of these biomarkers over time, and in relationship to treatment strategies, may provide prognostic information for pediatric patients with heart failure.

Prognostic Implications of Point-of-Care and Serial B-type Natriuretic Peptide Levels in Patients With Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HC) is a heterogenous disease with a variable clinical course. Predictors of long-term adverse cardiovascular events are needed. Our objectives were to determine the long-term prognostic value of a single and serial point of care (POC) B-type natriuretic-peptide (BNP) measurements in HC. One hundred and eleven ambulatory patients with HC (mean age 53 ± 16 years) were prospectively recruited over a 2-year period (2004 to 2006). A clinical assessment, comprehensive echocardiogram, and a POC BNP level was obtained at baseline and at a 1- to 2-year follow-up. They were subsequently followed for the occurrence of major adverse cardiac events (MACE). The median baseline BNP concentration was 114 pg/ml (range 5.3 to 1550 pg/ml). During a mean follow-up of 6.2 ± 3.4 years, 42 patients (38%) had a MACE. In a multivariable Cox model including clinical and echocardiographic predictors, logBNP (HR 4.30; 95% confidence interval 1.97 to 9.37, p <0.001) and left ventricualr ejection fraction (LVEF) (HR 0.96; 95% confidence interval 0.94 to 0.99, p = 0.011) remained significant predictors of MACE. Nested models demonstrated incremental prognostic value of logBNP for MACE (chi-square increased from 4.3 to 22.8, p <0.01) over clinical and echocardiographic factors. Patients with persistently elevated BNP (>100 pg/ml) at baseline and at the second visit were at a higher risk of developing MACE during follow-up (5-year MACE-free survival of 0.91 (SE 0.06) vs 0.45 (SE 0.09), p <0.001). In conclusion, POC BNP levels in patients with HC were predictive of long-term MACE and had independent and incremental value. Patients with persistently elevated BNP levels were at a higher risk of MACE.

Echocardiography with Elevated Central Venous Pressure Diagnosing Constrictive Pericarditis More Accurately Than Chest CT Scan: A Retrospective Study in 36 Cases.

Constrictive pericarditis (CP) is defined as impaired diastolic cardiac function caused by a calcified and thickened pericardium. We assessed the clinical characteristics and time to diagnosis, as well as patient prognosis after pericardiectomy.Methods: We analyzed the records of 36 CP patients who underwent pericardiectomy at Huashan Hospital, China, between 2012 and 2015. Clinical manifestations, length of time to diagnosis, laboratory parameters, and diagnostic imaging results were examined. All patients underwent pericardiectomy, and were assessed post-operatively for quality of life and improvement of cardiac function using the Minnesota Living with Heart Failure Questionnaire (MLHFQ).Results: All patients displayed shortness of breath and polyserous effusion, as well as elevated pro B-type natriuretic peptide and thickened pericardium. Mean time between onset of symptoms and a definitive diagnosis of CP was 9.5 ± 2.1 months. Pericardiectomy was performed within one week of diagnosis. Mean central venous pressure decreased from a pre-operative 19.92 ± 6.6 mmHg to a post-operative 8.5 ± 2.7 mmHg. Within 1.5 ± 0.7 years of surgery, all patients maintained good quality of life and cardiac function, which resulted in a mean score of 0.9 ± 0.6 on the MLHFQ.Conclusion: A definitive diagnosis of CP is usually made long after the onset of symptoms. Early detection and diagnosis by echocardiography with elevated central venous pressure and early treatment by surgery are key to an improved prognosis and resumption of good cardiac function.

Diagnostic value of lung ultrasound B-line score in acute heart failure

To investigate the value of bedside lung ultrasound B-line score in the diagnosis of acute heart failure (AHF). A retrospectively analysis was conducted. The adult patients presenting with acute dyspnea in intensive care unit (ICU) of Affiliated Hospital of Nanjing University of Traditional Chinese Medicine from January 2016 to June 2017 were enrolled. An 8-zone lung ultrasound was performed and plasma B-type natriuretic peptide (BNP) level was tested in all patients. AHF was determined as the final diagnosis by two experienced ICU doctors according to the diagnostic criteria of AHF. Patients were divided into two groups: AHF group and non-AHF group. The levels of BNP and B-line score were compared between the two groups, and the diagnostic value of BNP and B-line score in AHF was evaluated. Fifty-six patients were included in this study, with 32 of men and 24 of women, and with an average age of 77.3±8.8. Thirty-six patients were diagnosed as AHF. The level of BNP and lung ultrasound B-line score in AHF group were higher than those in non-AHF group [BNP (ng/L): 1 640.4±1 078.4 vs. 236.9±124.9, B line score: 12.8±5.3 vs. 5.4±1.8, both P < 0.01]. There was a strong correlation between elevated BNP levels and an increased B-lines score (R2 = 0.712, P = 0.000). The receiver operating characteristic curve (ROC) showed that when the cut-off of lung ultrasound B-line score was 8.5, AHF could be discriminated from dyspnea caused by other diseases (sensitivity was 77.8%, specificity was 95%, positive likelihood ratio was 15.56, negative likelihood ratio was 0.23). The area under the ROC curve (AUC) of lung ultrasound B-line score was 0.917 [95% confidence interval (95%CI) = 0.847-0.987, P = 0.000], slightly lower than that of plasma BNP [0.979 (95%CI = 0.951-1.008)]. Lung ultrasound B-line score was highly specific, but moderately sensitive for identifying patients with AHF.