Brain Natriuretic Peptide Values Research Articles

NLR-A Simple Indicator of Inflammation for the Diagnosis of Left Ventricular Hypertrophy in Patients with Hypertension.

This study included 386 patients with hypertension. Mann-Whitney U test and multivariate binary logistic regression analysis were used to investigate the relationship between NLR, CRP, BNP, and LVH in patients with hypertension, as well as compare the levels of NLR, CRP, and BNP in the four configurations. Receiver operator characteristic (ROC) curve was used to compare the diagnostic efficacy of NLR, CRP, and BNP on LVH. The NLR and CRP and BNP levels of the LVH group were significantly higher than those of the non-LVH group. In the multivariate logistic regression analysis, NLR as well as age, BMI, and SBP were associated with LVH. In addition, in patients with eccentric and concentric hypertrophy, the NLR and CRP and BNP levels were higher than those of the normal left ventricular geometry and concentric remodeling groups. The cutoff values of NLR, CRP, and BNP obtained by ROC curve were 2.185, 2.205, and 283.45, respectively, for the prediction of LVH. NLR is independently associated with LVH in patients with hypertension, and this is consistent with the diagnostic efficacy of CRP and BNP, which may be a simple and convenient indicator for judging LVH.

Silent coronary artery disease in asymptomatic patients with severe aortic stenosis and normal exercise testing.

There are no data about the prevalence of silent coronary artery disease in asymptomatic severe aortic stenosis patients with normal exercise testing. Importantly, unmasking significant coronary artery disease in patients with aortic stenosis could influence the choice/timing of treatment in these patients. Exercise testing was performed on semi-supine ergobicycle. Cardiopulmonary analysis during exercise testing, echocardiography, and laboratory analysis at rest was done. Standard clinical/electrocardiography criteria were assessed for symptoms/signs of ischemia during/after exercise testing. In patients with normal exercise testing coronary angiography was performed using standard femoral/radial percutaneous approach. Coronary stenosis was considered significant if >70% of vessel diameter or 50%-70% with fractional flow reserve ≤0.8. Total of 96 patients with normal exercise testing were included (67.6 years, 50.6% males). No patient had any complication or adverse event. The Pmean was 52.7 mmHg, mean indexed aortic valve area was 0.36 cm/m and left ventricular ejection fraction, 69.5%. 19/96 patients (19.8%) had significant coronary artery disease on coronary angiography. Multivariate logistic regression analysis revealed brain natriuretic peptide and blood glucose as independent predictors of silent coronary artery disease. Brain natriuretic peptide value of 118 pg/ml had sensitivity/specificity of 63%/73% for predicting coronary artery disease (area under the curve 0.727, P = 0.006). Our results are the first to show that in patients with severe aortic stenosis, normal left ventricular ejection fraction,, and normal exercise testing, significant coronary artery disease is present in as many as 1/5 patients. In such patients, further prospective studies are warranted to address the diagnostic value of brain natriuretic peptide in detecting silent coronary artery disease.

621 Anemia and its impact on clinical, echocardiographic parameters and prognosis in patients with severe aortic stenosis and normal left ventricular ejection fraction

Abstract Background Anemia is common in patients (pts) with severe aortic stenosis (AS). Untreated anemia and severe AS are individually associated with the development of heart failure, however data regarding the potential detrimental effect of anemia on left ventricular (LV) function and prognosis in pts with severe AS are controversial. Aim To investigate the impact of anemia on clinical status, echocardiographic parameters and prognosis in pts with severe AS and preserved LV ejection fraction (LVEF). Methods Consecutive patients with severe AS (aortic valve area [AVA] index ≤ 0.6 cm2/m2) and preserved LVEF (>50%) referred to our echocardiography laboratory were prospectively screened. All patients underwent complete clinical examination and comprehensive echocardiography, including speckle tracking-derived measurements of LV and left atrial (LA) strain. Baseline clinical variables included NYHA class, cardiac risk factors, haemoglobin (Hb) level and glomerular filtration rates (GFR, by MDRD formula). The definition of anemia was based on gender-specific cut-off values, as recommended by the WHO (Hb <13.0 g/dL for men, <12.0 g/dL for women). Patients with more than mild aortic regurgitation or mitral valve disease, atrial fibrillation or cardiac pacemakers were excluded. Results The study population included 264 patients (pts) (66 ± 11 yrs, 147 men). Anemia was present in 64 pts (24%). Aortic valve replacement (AVR) was performed in 151 pts. Dividing the study population into 2 groups, according to the presence/absence of anemia, no significant differences were found between groups regarding: age (p = 0.09), body surface area (p = 0.6), LVEF (62 ± 7 vs 63 ± 6%, p = 0.2), LV Global Longitudinal Strain (-15.2 ± 4 vs -14.7 ± 3 %, p = 0.4), LV mass index (p = 0.9), mean aortic gradient (p = 0.2) and indexed AVA (0.40 ± 0.09 vs 0.39 ± 0.09 cm2/m2, p = 0.6), or presence of significant coronary artery disease (p = 0.9). Compared to pts with normal Hb level, in pts with anemia NYHA class (p = 0.03), brain natriuretic peptide values (p = 0.004), lateral E/e’(16.2 ± 6.9 vs 13.7 ± 6.3, p = 0.01) and average E/e" ratio (15.9 ± 5.9 vs 14.1 ± 5.3, p = 0.03), LA volume index (54.3 ± 16.9 vs 45.0 ± 12.1 ml/m2, p < 0.001), and systolic pulmonary artery pressure (38 ± 13 vs 33 ± 8, p = 0.009) were all significantly higher. During a 3–years follow-up 47 pts died. Age, NYHA class, BNP serum level, baseline anemia, LA volume index and systolic pulmonary pressure were associated with all-cause mortality in the whole study group (p < 0.03 for all). In the group of pts who underwent AVR, NYHA class was the only independent predictor of all-cause mortality. Conclusions In our study including pts with severe AS and preserved LVEF, patients with baseline anemia presented worse functional status and LV diastolic dysfunction and increased 3-year all-cause mortality compared to those with normal Hb levels. However, in pts who underwent surgical AVR, there was no impact of baseline anemia on 3-year survival.

Impact of oxidative posttranslational modifications of SERCA2 on heart failure exacerbation in young patients with non-ischemic cardiomyopathy: A pilot study

BackgroundOxidative posttranslational modifications (OPTM) impair the function of Sarcoplasmic/endoplasmic reticulum (SR) calcium (Ca2+) ATPase (SERCA) 2 and trigger cytosolic Ca2+ dysregulation. We investigated the extent of OPTM of SERCA2 in patients with non-ischemic cardiomyopathy (NICM). Methods and resultsEndomyocardial biopsy (EMB) was obtained in 40 consecutive patients with NICM. Total expression and OPTM of SERCA2, including sulfonylation at cysteine-674 (S-SERCA2) and nitration at tyrosine-294/295 (N-SERCA2), were examined by immunohistochemical analysis. S-SERCA2 increased in the presence of late gadolinium enhancement on cardiac magnetic resonance imaging. S-SERCA2/SERCA2 and N-SERCA2/SERCA2 correlated with cardiac fibrosis evaluated by Masson’s trichrome staining of EMB. SERCA2 expression modestly increased in parallel with an upward trend in OPTM of SERCA2 with aging. This tendency became prominent only in patients aged >65 years. OPTM of SERCA2 positively correlated with brain natriuretic peptide (BNP) values only in patients aged ≤65 years. Composite major adverse cardiac events (MACE) increased more in the high OPTM group of younger patients; however, MACE-free survival was similar irrespective of the extent of OPTM in older patients. ConclusionsOPTM of SERCA2 correlate with myocardial fibrosis in NICM. In younger patients, OPTM of SERCA2 correlate with elevated BNP and increased composite MACE.

Potential Value of Native T1 Mapping in Symptomatic Adults with Congenital Heart Disease: A Preliminary Study of 3.0 Tesla Cardiac Magnetic Resonance Imaging.

The native T1 value at 3.0 Tesla is a sensitive marker of diffuse myocardial damage. We evaluated the clinical usefulness of native T1 mapping in symptomatic adults with congenital heart disease (CHD), particularly in the systemic right ventricle (RV). Prospectively, 45 consecutive symptomatic adults with CHD were enrolled: 20 with systemic RV and 25 with tetralogy of Fallot underwent cardiac magnetic resonance (CMR) imaging at 3.0 Tesla. The Modified Look-Locker Inversion recovery sequence was used for T1 mapping. Cardiovascular events in the systemic RV were defined as heart failure and tachyarrhythmia. Brain natriuretic peptide (BNP) and indexed systemic ventricular end-diastolic volume were significantly higher in the systemic RV group. The native T1 value and extracellular volume (ECV) of the septal and lateral walls were higher in the systemic RV group, suggesting high impairment of the myocardium in the systemic RV group. There was a strong correlation between the native T1 value and ECV of the septum (r = 0.58, P = 0.03) and lateral wall (r = 0.56, P = 0.046) in the systemic RV group. Seven patients with systemic RV had cardiovascular events. In univariate logistic regression analysis, BNP and native T1 values of the insertion point were important for predicting cardiovascular events. The native T1 value at 3.0 Tesla may be a sensitive, contrast-free, and non-invasive adjunct marker of myocardial damage in CHD and predictive of cardiovascular events in the systemic RV.

P3536Prevalence and clinical impact of social frailty in elderly patients hospitalized for acute decompensated heart failure: a multicenter prospective cohort study

Abstract Purpose The aim of this study was to investigate clinical characteristics of socially frail patients and an association with social frailty and short-term rehospitalization for worsening heart failure. Methods We analyzed 169 elderly patients (≥65 years old) hospitalized for acute decompensated heart failure (ADHF) between June 2017 and August 2018 in our prospective HF registry in Japan. The patients with activities of daily living dependence and without data of social frailty and outcome were excluded. Social frailty was determined based on their responses to the 5 questions (living alone, eating alone, going out less frequently, rarely visiting friends, not helpful to friends or family). Patients with none of these components were considered social non-frailty; those with one component were considered social prefrailty; those with two or more components were considered social frailty. The outcome was rehospitalization for worsening HF within 6 months after discharge. Results The mean age was 79±8 years old. Social frailty in 86 patients (50.8%), social prefrailty in 41 patients (24.3%), and social non-frailty in 42 patients (24.9%) were observed. Age, body mass index, geriatrics nutritional risk index, Hasegawa dementia rating scale-revised score, gait speed, and handgrip strength values were significantly different among the these three groups (all Ps for trend <0.01). Left ventricular ejection fraction, brain natriuretic peptide values, and the proportion of the patients with the symptom of New York Heart Association class III/IV did not vary significantly between the groups. Kaplan-Meier analysis revealed that higher prevalence of rehospitalization for worsening HF within 6 months in the social frailty group compared to that in the social non-frailty group (Log-rank p<0.05). In a Cox proportional hazard model after adjusting covariates, patients with social frailty (hazard ratio 4.77; 95% CI 1.61–14.12, p<0.005) and social prefrailty (hazard ratio 3.73; 95% CI 1.12–12.41, p<0.05) had an increased risk of rehospitalization for worsening HF within 6 months compared with those with social non-frailty. Conclusion This study revealed that social frailty was common in elderly patients hospitalized for ADHF, and social frailty was an independent predictor of rehospitalization for worsening HF within 6 months after discharge.

P4736The Prognostic Impact of Volume Substitution on Cardiac Strain and the Development of Postoperative Atrial Fibrillation after Cardiac Surgery

Abstract Background Postoperative atrial fibrillation (POAF) represents a common complication after cardiac valve or coronary artery bypass surgery. Etiologically, multifactorial causes such as the patients' age, weight, comorbidities or local remodeling proved a strong association with this common arrhythmia. While strain of atrial tissue is known to induce atrial fibrillating impulses, less attention has been paid to potentially strain-promoting values during the peri- and post-operative period. Therefore, we aimed to determine the association of peri- and post-operative volume substitution on markers of cardiac strain and subsequently its impact on the promotion and development of POAF. Methods In this prospective observational study 271 patients undergoing elective cardiac surgery in our Medical University were enrolled (median age: 69 years [IQR: 60–75 years]; 195 [72%] male gender). Intra- and post-operative data was collected from anesthesiologic and intensive care unit protocols. Multivariate binary logistic regression analysis was used to identify the prognostic value of volume substitution on the development of POAF. Results A total of 123 (45.4%) individuals developed POAF. The average intra-operative transfusion volume was significantly elevated in the POAF subgroup (605.6ml [POAF] vs. 227.1ml [non-POAF]; p<0.001). Moreover, the fluid balance within the first 24 hours after surgery was significantly higher in patients developing POAF (+1129.6 ml [POAF] vs. +544.9 ml [non-POAF]; p=0.044). We found that N-terminal pro brain natriuretic peptide (NT-proBNP) values were significantly elevated in patients that received any volume substitution (2860.0 pg/mL [Transfusion] vs. 1486.5 pg/mL [no-Transfusion]; p=0.002). In line with those results, the postoperative fluid balance was also found to have a direct and significant correlation with postoperative NT-ProBNP values (r=0.287, p=0.002). Of note, the amount of substituted volume proved to be a strong and independent predictor for POAF with an adjusted odds-ratio (OR) per one standard deviation (1-SD) of 2.49 (95% CI: 1.25–4.96; p=0.009). Conclusion Within the present analysis we were able to demonstrate that substitution of larger transfusion volumes presents a strong and independent predictor for the development of POAF. Via the observed distinct association with NT-proBNP values, it can reasonably be assumed that post-operative atrial fibrillating impulses are triggered via volume-induced cardiac strain.

P1030Elevated baseline brain natriuretic peptide level was associated with poor outcome after multiple catheter ablation for paroxysmal atrial fibrillation

Abstract Background Serum Brain Natriuretic Peptide (BNP) level is associated with various cardiovascular events. Because elevated BNP level reflects increased left ventricular end-diastolic pressure and LA pressure promoting left atrial (LA) remodeling, BNP level might be associated with the extent of arrhythmogenic substrate in patients with atrial fibrillation (AF). We hypothesized that elevated BNP level has impact on outcome after catheter ablation (CA) for AF. Purpose We investigated the impact of baseline BNP level on outcome after multiple CA for paroxysmal atrial fibrillation (PAF), and assessed the association between baseline BNP level and extent of LA remodeling. Methods This was a retrospective, single-center observational study. A total of 287 patients who underwent CA for PAF in our institute from March 2012 to March 2014. All patients had dataset of baseline BNP level and LA volume measured by multi-detector computed tomography (MDCT) in sinus rhythm. First we performed receiver operating characteristic (ROC) analysis for recurrence after multiple CA and obtained the best cut-off value of BNP. Patients were divided into Low BNP and High BNP group based on BNP cut-off value, and AF-free survival was analyzed with log-rank test. To assess the impact of BNP level on recurrence, multivariate Cox regression model were performed. Finally, we assessed the extent of baseline LA remodeling in low BNP and high BNP group. Results During follow-up period, AF recurred in 65/287 patients (26.2%) after multiple CA procedure (follow up 3.4 [2.2, 4.0] years, total number of sessions: 1.39±0.63). Patients with recurrence had greater baseline BNP than those without recurrence (99.8 pg/mL [30.0, 128] vs. 60.7 pg/mL [17.3, 80.8], recurrence vs. no-recurrence, P<0.05). In ROC analysis, baseline BNP had mild accuracy for the prediction of recurrence (AUC: 0.63, P=0.002, best cut-off value: 57.3 pg/mL). We divided patients into High BNP group (BNP≥57.3, N=106) and Low BNP group (BNP<57.3, N=181). AF-free survival was higher in Low BNP than in High BNP (Figure 1) (83.4% vs. 67.0%, Low vs. High, P<0.001). After adjustment with age, gender, hypertension, heart failure, body mass index, LA diameter and LV ejection fraction, High BNP (BNP≥57.3) was associated with recurrence (Hazard ratio: 2.31, 95% CI 1.42–3.75, P<0.001). In baseline parameters of LA remodeling measured with MDCT, Low BNP group had higher LA emptying fraction (41.7±9.5 vs. 32.0±8.5%, Low vs. High, P<0.001) and lower indexed maximum LA volume (48.5±12.0 vs. 61.3±16.7 mL/m2, P<0.001) (Figure 2). Conclusion Baseline serum BNP level was associated with recurrence after multiple procedures for PAF. The baseline extent of LA remodeling was greater in High BNP than in Low BNP. Elevated BNP level might reflect the severe LA remodeling causing ablation-refractory AF even after multiple CA. The preoperative assessment of BNP might be helpful for prediction of multiple CA outcome.

939 B-Type Natriuretic Peptide Predicts 90-Day Mortality and Need for Paracentesis in Patients With Cirrhosis and Without Systolic Heart Failure

INTRODUCTION: Fluid overload is the most frequent complication of end-stage liver disease, regardless of its etiology. Levels of brain natriuretic peptide (BNP) have been shown to be elevated in cirrhotic patients when matched to healthy subjects. There are only small observational studies done in Asian and European populations evaluating the role of BNP in predicting mortality of patients with liver disease. The use of BNP to predict 90-day requirement of paracentesis has not been studied. METHODS: Retrospective analysis of medical records of patients with a diagnosis of cirrhosis without heart failure, arrhythmia, coronary artery disease or pulmonary hypertension from John H. Stroger Hospital of Cook County Medical Record's database from 2008 to 2018. IRB approval was obtained. All analysis was done using STATAv14. RESULTS: The cohort included 430 patients with clinical and radiological diagnosis of cirrhosis without systolic dysfunction of which 12% had BNP ≥ 300 pg/mL. Patients with BNP ≥ 300 pg/mL were younger (53.3 vs 55.6 years, P = 0.027), had less proportion of hepatitis B (0% vs 100%, P = 0.013), hepatitis C (7.4% vs 92.6%, P = 0.036), higher mean number of paracentesis (1.60 vs 2.52, P = 0.005), creatinine (2.66 vs 1.03 mg/dL, P=< 0.001), bilirubin (5.36 vs 2.84 mg/dL, P=< 0.001) and INR levels (1.75 vs 1.50, P = 0.003). There was no significant difference in Child-Pugh class between the two groups and MELDNa scores were significantly higher in the BNP ≥ 300 pg/mL group. Kaplan-Meier survival estimates for death within 90 days show increased significant mortality [HR 3.49, P = 0.037] and significantly higher requirement for paracentesis in 90 days [HR 2.26, P = 0.020] with levels of BNP ≥ 300 pg/mL. CONCLUSION: This is, to our knowledge, the largest study done to assess BNP as a prognostication tool in cirrhotic patients. Despite excluding patients with overt cardiac dysfunction, we found that higher BNP levels are significantly associated with higher medium-term mortality, paracentesis requirements and higher MELDNa scores, suggesting high BNP values as an indicator of severity. The presence of hepatitis B and C seem to be a protective factor, most likely due to possible less indolent disease and more accessible treatment methods. In conclusion, BNP seems to be a reliable predictor of severity in this cohort of patients.

Impact of aortic stenosis on layer-specific longitudinal strain: relationship with symptoms and outcome.

The present study sought to assess the impact of aortic stenosis (AS) on myocardial function as assessed by layer-specific longitudinal strain (LS) and its relationship with symptoms and outcome. We compared 211 patients (56% males, mean age 73 ± 12 years) with severe AS and left ventricular ejection fraction (LVEF) ≥50% (114 symptomatic, 97 asymptomatic) with 50 controls matched for age and sex. LS was assessed from endocardium, mid-myocardium, and epicardium by 2D speckle-tracking echocardiography. Despite similar LVEF, multilayer strain values were significantly lower in symptomatic patients, compared to asymptomatic and controls [global LS: 17.9 ± 3.4 vs. 19.1 ± 3.1 vs. 20.7 ± 2.1%; endocardial LS: 20.1 ± 4.9 vs. 21.7 ± 4.2 vs. 23.4 ± 2.5%; epicardial LS: 15.8 ± 3.1 vs. 16.8 ± 2.8 vs. 18.3 ± 1.8%; P < 0.001 for all]. On multivariable logistic regression analysis, endocardial LS was independently associated to symptoms (P = 0.012), together with indexed left atrial volume (P = 0.006) and LV concentric remodelling (P = 0.044). During a mean follow-up of 22 months, 33 patients died of a cardiovascular event. On multivariable Cox-regression analysis, age (P = 0.029), brain natriuretic peptide values (P = 0.003), LV mass index (P = 0.0065), LV end-systolic volume (P = 0.012), and endocardial LS (P = 0.0057) emerged as independently associated with cardiovascular death. The best endocardial LS values associated with outcome was 20.6% (sensitivity 70%, specificity 52%, area under the curve = 0.626, P = 0.022). Endocardial LS (19.1 ± 3.3 vs. 20.7 ± 3.3, P = 0.02) but not epicardial LS (15.2 ± 2.8 vs. 15.9 ± 2.5, P = 0.104) also predicted the outcome in patients who were initially asymptomatic. In patients with severe AS, LS impairment involves all myocardial layers and is more prominent in the advanced phases of the disease, when the symptoms occur. In this setting, the endocardial LS is independently associated with symptoms and patient outcome.

Difference in Serological Marker Profile of Fontan Patients with Decompensated Heart Failure

Introduction As survival rates of patients born with univentricular heart defects and palliated by the Fontan operation increase, Fontan failure is more frequently encountered in the adult years. The evidence for use of serological markers, including the brain natriuretic peptide (BNP), at the time of acute Fontan failure exacerbations has been limited in this patient population. Hypothesis We hypothesize that among patients with a Fontan circulation admitted for decompensation, serological markers, particularly BNP, will have a different profile when compared to the general heart failure population. Methods This was a single center retrospective study of Fontan patients who were admitted for acute decompensated Fontan failure. The patients underwent a 1:2 propensity match for age, gender and renal function with non-Fontan patients for each hospital encounter. Admission laboratory values and echocardiographic findings were collected and verified. Student's t-test and chi-square test were used for comparison between the two patient groups. A logistic regression model assessed association of patients’ variables with a length of stay greater than 3 days. Results Our study cohort consisted of 54 encounters for 20 Fontan patients with median age of 34 years and 108 encounters for 108 non-Fontan patients with a median age of 35 years. BNP levels were significantly lower in Fontan patients admitted for decompensation (p Conclusion Compared to the general heart failure population with structurally normal hearts, the BNP values in Fontan patients admitted due to decompensation are lower on admission with a smaller change from the last known outpatient value. Alternative laboratory studies profile should likely be used for risk stratification in this patient population.

Biomarkers of prehypertension and hypertension in women

The percentage of undiagnosed prehypertensive and hypertensive women are high in the population of Kazakhstan. Our study assessed biomarkers in prehypertension and hypertension in women. 203 women were divided into 3 groups: “pre-hypertensive” group ( n = 30, 46.6 ± 6.2 y.o.) with a systolic blood pressure from 120 to 139 mmHg or/and a diastolic blood pressure from 80 to 89 mm Hg. In the “hypertensive” group the blood pressure was > = 140/90 mmHg ( n = 73, 46.6 ± 5.6 y.o.). In the normotensive group the blood pressure was < = 120/80 mm Hg ( n = 100, 44.2 ± 5.9 y.o.). The MILLIPLEX MAP Human CVD 1 Magnetic Bead kit was used for the quantification of cardiovascular biomarkers in venous samples. The quantification of the level of cardiac markers was carried out on the Bio-Plex®3D multiplex analyzer Suspension Array System (Bio-Rad Laboratories, Inc., USA). The values of brain natriuretic peptide (BNP), creatine kinase-MB (CK MB), and leptin were statistically increased in women depending on their blood pressure. The BNP values in the hypertensive group (Me = 157.9 pg/ml, Q 1 = 53.75 pg/ml and Q 3 = 229.6 pg/ml) were statistically greater (p = 0.016) than in the normotensive group (Me = 85.14 pg/ml, Q 1 = 18.55 pg/ml and Q 3 = 113.9 pg/ml). The BNP values in the prehypertension group were greater than in the normotensive group and less than in the hypertensive group (Me = 73.00 pg/ml, Q 1 = 35.52 pg/ml and Q 3 = 139.4 pg/ml). The CK MB values in the hypertensive group (Me = 3693 pg/ml, Q 1 = 3105 pg/ml and Q 3 = 6178 pg/ml) were statistically higher (p = 0.022) than in the normotensive group (Me = 2688 pg/ml, Q 1 = 1629 pg/ml and Q 3 = 4532 pg/ml). The CK MB values in the prehypertension group were greater than in the normotensive group and less than in the hypertensive group (Me = 2722 pg/ml, Q 1 = 1833 pg/ml and Q 3 = 5266 pg/ml). In addition, the values of leptin in the hypertensive group (Me = 23910 pg/ml, Q 1 = 14510 pg/ml and Q 3 = 54824 pg/ml) were statistically greater (p = 0.001) than in the normotensive group (Me = 18256 pg/ml, Q 1 = 9287 pg/ml and Q 3 = 34843 pg/ml). The leptin values in the prehypertension group were: Me = 26424 pg/ml, Q 1 = 10514 pg/ml and Q 3 = 53060 pg/ml. In hypertensive women, serum BNP, CK-MB and leptin levels were significantly different from the same parameters in control women. Pre-hypertensive patients were in-between the normotensive and the hypertensive groups. However, biomarkers were not statistically different in women with prehypertension and those from the two other groups. Thus, patients with pre-hypertension cannot longer be attributed to healthy individuals although, they have not yet pronounced clinical and laboratory signs of arterial hypertension, the mechanisms of arterial hypertension are already running. Our results showed that there is need to develop recommendations for the identification and monitoring of patients with pre-hypertension in order to prevent the development of irreversible cardiovascular alterations.

Multiparametric approach to congestion for predicting long-term survival in heart failure

BackgroundCongestion is a marker of adverse prognosis in patients with heart failure (HF). In addition to brain natriuretic peptide (BNP), estimated plasma volume status (ePVS), bioimpedance vector analysis (BIVA), and blood urea nitrogen/creatinine ratio (BUN/Cr) are emerging as new markers for congestion. The aim of this study was to evaluate the prognostic value of BNP, ePVS, BIVA, and BUN/Cr in HF. MethodsWe analyzed the data from 436 patients with acute or chronic heart failure (AHF, n=184, and CHF, n=252, respectively). BNP, ePVS, hydration index (HI%), and BUN/Cr were collected from all patients at admission. The endpoint was all-cause mortality. ResultsNinety-two patients died after a median follow-up of 463 days (IQR: 287–669). The cumulative mortality of all of the patients was 21% (31% and 13% in AHF and CHF, respectively, p<0.0001). The optimal cut-offs for death occurrence were BNP: >441pg/mL, ePVS: >5.3dL/gr, HI: >73.8%, BUN/Cr: >25. Multivariate Cox regression analysis maintained an independent predictive value for mortality (HR 2. 1, HR 2.2, HR 2.1, and HR 1.7; C-index 0.756). AHF status was no longer associated with death. Together, these variables explained 40% of the risk of death (R2 adjusted=0.40). Patients with all four parameters below or above their optimal cut-off had mortality rates of 4% and 59%, respectively. ConclusionsBNP, ePVS, BIVA, and BUN/Cr at admission provide independent and complementary prognostic information in patients with HF and, when combined, explain the 40% risk of death in these patients independent from the acute or chronic HF condition.

SAT-262 RATIONALE AND DESIGN OF “CARDINAL”: A PHASE 2/3 STUDY OF THE EFFICACY AND SAFETY OF BARDOXOLONE METHYL IN PATIENTS WITH ALPORT SYNDROME

Alport syndrome, a rare and serious hereditary disease with no approved pharmacological therapy, is caused by mutations in the genes encoding type IV collagen that result in structural defects of the glomerular basement membrane resulting in inflammation, remodeling, fibrosis, and loss of kidney function. Through induction of Nrf2 and suppression of NF-κB, bardoxolone methyl (Bard) and related analogs improve renal function, reduce inflammation, and prevent fibrosis in multiple animal models of renal injury and disease. In previous clinical studies that enrolled over 2,600 patients, including primarily patients with chronic kidney disease (CKD) caused by type 2 diabetes, Bard improved estimated and measured GFR as assessed by inulin clearance. A Phase 2/3 trial was designed to test the hypothesis that Bard will improve renal function in patients with Alport syndrome. The Phase 2/3 trial of the Efficacy and Safety of Bardoxolone Methyl in Patients with Alport Syndrome (CARDINAL NCT03019185) is a double-blind, randomized, placebo-controlled, multinational, multicenter study that will enroll approximately 150 patients on stable RAAS blockade, ages 12 to 70 years with confirmed genetic or histologic diagnosis of Alport syndrome, eGFR values between 30 to 90 mL/min/1.73 m2, and albumin to creatinine ratio ≤ 3500 mg/g. Patients with brain natriuretic peptide (BNP) values > 200 pg/mL at baseline or with significant cardiovascular histories, including left ventricular ejection fraction < 40% (based on echocardiogram), are excluded. The primary efficacy endpoint will be the change from baseline in eGFR in Bard-treated patients relative to placebo after 48 weeks of treatment. The key secondary endpoint will be the change from baseline in eGFR in Bard-treated patients relative to placebo at Week 52 following a 4-week drug treatment withdrawal period. The 4 week withdrawal period represents 17 half-lives of the drug and is associated with 1) sub-therapeutic serum Bard concentrations, 2) return to baseline of pharmacodynamic markers of Nrf2 activation, 3) and loss of pharmacologic activity. All patients enrolled in the study will be followed for two years. The open-label Phase 2 portion of the CARDINAL trial enrolled 30 subjects and showed that Bard significantly increased eGFR in patients with Alport syndrome after 12 weeks of treatment and these improvements were sustained for up to 48 weeks (+10.4 mL/min/1.73 m2; n=25; p<0.0001). Bard also resulted in a significant retained benefit of +4.1 mL/min/1.73 m2 4 weeks post-drug withdrawal. Urinary albumin to creatinine ratios were not significantly different from baseline at Weeks 48 or 52. The Phase 3 portion enrolled 157 patients and data are not yet available. Initial 1-year data from the Phase 2 portion of CARDINAL, in particular the retained benefit after Bard is stopped, support that the mechanism by which Bard increases eGFR is not harmful and may even suggest disease-modifying activity in patients with Alport syndrome. The Phase 3 portion of CARDINAL is the first randomized, placebo-controlled trial to test the hypothesis that Bard will slow the progression of CKD in patients with Alport syndrome.

The utility of brain natriuretic peptides in septic shock as markers for mortality and cardiac dysfunction: A systematic review.

To conduct a systematic review evaluating the utility of brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) as biomarkers in adult patients with septic shock. Pubmed/Medline databases were searched from inception to November 2018 using the search terms: (septic[Title/Abstract] AND shock[Title/Abstract]) AND bnp[Title/Abstract]) and (septic[Title/Abstract]) AND shock[Title/Abstract]) AND natriuretic[Title/Abstract]). No restriction was applied regarding date of publication. Comparative observational studies evaluating BNP and NT-proBNP in patients with septic shock aged ≥18years were eligible for inclusion. Bibliographies from the extracted articles were also reviewed to identify additional relevant publications. In total, 46 studies met all eligibility criteria and were included. A strong body of literature has demonstrated that in patients with septic shock, increased values of BNP and NT-proBNP are associated with increased mortality. An increase from baseline BNP values has also been associated with increased mortality, whereas decreases from baseline values are not related to worse outcome. Brain natriuretic peptides have also been associated with cardiac dysfunction in patients with sepsis. Moreover, BNP values have been found to be significantly elevated in septic shock, regardless of cardiac dysfunction, and have been used to distinguish between septic and cardiogenic shock. Furthermore, BNP and NT-proBNP are significantly increased in patients with septic shock, compared to patients with sepsis and severe sepsis. BNP and NT-proBNP appear to be reliable predictors of outcome in septic shock.

Increased Plasma Soluble Fractalkine in Patients with Chronic Heart Failure and Its Clinical Significance

Fractalkine has been reported to play an important role in the pathophysiology of various cardiovascular disorders. This research aims to study the change of soluble fractalkine (sFKN) in plasma level of patients with chronic heart failure (CHF) and evaluate its prognostic value.A total of 96 patients with CHF and 45 healthy subjects were included in this study. The plasma levels of sFKN, brain natriuretic peptide (BNP), and Interleukin-18 (IL-18) were determined by ELISA kits when they were first admitted to the hospital. Left ventricular ejection fraction (LVEF) was measured by echocardiogram. Rehospitalization status within 1 year after the first hospitalization was also recorded.The plasma levels of sFKN, BNP, and IL-18 in patients with CHF were significantly higher than in the control group (P < 0.05). The concentrations of sFKN and BNP were increased with the severity of heart failure classified by NYHA classification (P < 0.05). There were no statistical differences among all CHF subgroups classified by etiology (P > 0.05). Plasma sFKN level in CHF group was positively correlated with BNP (r = 0.441, P < 0.001) and IL-18 (r = 0.592, P < 0.001). Receiver operating characteristic curve analysis showed that area under the curve values of FKN, BNP, and IL-18 were 0.885 (95%CI: 0.810 to 0.960, P < 0.001), 0.889 (95%CI: 0.842 to 0.956, P < 0.001), and 0.878 (95%CI: 0.801-0.954, P < 0.001), respectively. The concentrations of sFKN and BNP were increased in patients readmitted more than once within 1 year (P < 0.05).

Different inflammatory profile in young and elderly STEMI patients undergoing primary percutaneous coronary intervention (PPCI): Its influence on no-reflow and mortality

BackgroundCoronary no-reflow phenomenon in ST-segment elevation myocardial infarction (STEMI) is associated with a poor clinical prognosis. Although its pathophysiology is not fully elucidated, a deregulated systemic inflammatory response plays an important role. Specifically, the relationship between age-associated differences in inflammatory markers and either no-reflow or mortality in STEMI patients undergoing primary percutaneous coronary intervention (pPCI) has never been investigated. Methods and resultsWe retrospectively enrolled 625 consecutive STEMI patients undergoing pPCI for whom a complete laboratory inflammatory pattern was available. Routinely blood measured laboratory parameters were collected at the moment of admission. No reflow was defined as Thrombolysis in Myocardial Infarction (TIMI) flow-grade lower than 3. The population was divided into two groups using a cut-off centered at 65 years. Compared to younger patients, elderly patients had higher mean values of fibrinogen, brain natriuretic peptide (BNP), leukocytes, neutrophil-to-lymphocyte ratio (NLR), C reactive protein/albumin ratio (CAR). Conversely, lymphocyte count and albumin levels were higher in young patients. In elderly patients, the values of NLR, CAR as well as leukocytes, fibrinogen and neutrophils were associated with no-reflow, while in young patients only BNP value was associated. At multivariate Cox regression analysis, only BNP and NLR resulted as independent predictors of all-cause mortality in the whole population and in elderly patients. ConclusionsElderly STEMI patients on admission had a higher acute pro-inflammatory profile than young patients, associated to coronary no-reflow and mortality outcome. These results suggest that a different therapeutic approach between elderly and young STEMI patients should be agreed.

Correlations of Changes in Brain Natriuretic Peptide (BNP) and Cardiac Troponin I (cTnI) with Levels of C-Reactive Protein (CRP) and TNF-α in Pediatric Patients with Sepsis.

BackgroundThis study investigated the changes in plasma brain natriuretic peptide (BNP) and cardiac troponin I (cTnI) levels in pediatric patients with sepsis, and explored their relationships with serum inflammatory factors in pediatric patients.Material/MethodsA total of 120 pediatric patients with sepsis admitted to and treated at our hospital from 2013 to 2017 were divided into 4 groups: a systemic inflammatory response syndrome (SIRS) group (n=28), a sepsis group (n=35), a severe sepsis group (n=27), and a septic shock group (n=30). Plasma BNP, cTnI, and creatine kinase-MB (CK-MB) levels in pediatric patients in the 4 groups were measured, and the correlations of BNP and cTnI with plasma inflammatory factors C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α) were investigated.ResultsThe plasma BNP and cTnI levels in pediatric patients with sepsis were significantly higher than those in the SIRS group (p<0.05). After hospitalization and treatment, levels of BNP and cTnI in pediatric patients were decreased. The concentrations of BNP and cTnI were correlated with CRP level (r=0.88 and 0.88, respectively). The associations (r value) of BNP and cTnI with TNF-α levels were 0.35 and 0.48, respectively.ConclusionsThe levels of plasma BNP and cTnI are associated with the severity of sepsis in pediatric patients, and were positively correlated with CRP and TNF-α levels, which provides a novel strategy for the early diagnosis and evaluation of sepsis in pediatric patients.

Screening Echocardiography and Brain Natriuretic Peptide Levels Predict Late Pulmonary Hypertension in Infants with Bronchopulmonary Dysplasia.

Through this study, we aimed to assess the ability of routine neonatal screening at time of bronchopulmonary dysplasia (BPD) diagnosis to predict the development of late pulmonary hypertension (PHTN). This is a retrospective longitudinal cohort study of 37 premature infants with BPD assessing the utility of screening serum brain natriuretic peptide (BNP) and echocardiograms performed at the time of BPD diagnosis ('early PHTN') to predict 'late PHTN' at the last follow-up. Screening evaluation demonstrated early PHTN in 9/37 patients. At an average follow-up interval of 52.7 ± 38.7weeks, 4/9 had late PHTN; one patient without early PHT had late PHT. At initial screening, infants with late PHTN were significantly more likely to have demonstrated elevated BNP values (p = 0.003), and echocardiographic evidence of right atrial dilatation (p = 0.01), right ventricular hypertrophy (p = 0.01), lower right ventricular area change percentage (p = 0.03), and larger main pulmonary artery Z-scores (p = 0.02). Serum BNP and echocardiographic evaluation performed at the time of BPD diagnosis can detect patients at increased risk of late PHTN. Large, prospective studies are necessary to further address this question.

The clinical value of brain natriuretic peptide and soluble urokinase plasminogen activator receptor in the diagnosis and prognosis of bloodstream infection in the patients of Intensive Care Unit

Objective To study the clinical value of brain natriuretic peptide (BNP) and soluble urokinase plasminogen activator receptor (suPAR) in the diagnosis and prognosis of bloodstream infection. Methods Totally 165 patients suspected of bloodstream infection admitted in intensive care unit (ICU) of the Second Hospital Affiliated to Suzhou University were enrolled in this study. According to the diagnosis standard of bloodstream inflection, patients were divided into the bloodstream infection group and non-bloodstream infection group. According to the prognosis of the patients, the bloodstream infection group was further divided into the survival group and the death group. Serum levels of suPAR, BNP, CRP, PCT, and chronic health evaluation Ⅱ acute physiology score (APACHE Ⅱ ), and mortality of the patients were analyzed, and the possible relation of the above indexes between the two groups were compared. Based on the receiver operating characteristic curve (ROC) and the area under the curve (AUC), the early diagnostic value of suPAR, BNP, CRP, PCT, and APACHE Ⅱ score in the bloodstream infection patients was determined. Results Serum levels of suPAR, BNP, CRP, PCT and APACHE II score in the bloodstream infection group were higher than those in the non-bloodstream infection group (P<0.05); Serum levels of suPAR, BNP, CRP, PCT and APACHE Ⅱ score in the death group were higher than those in the survival group (P<0.05). There was a positive correlation between serum suPAR, BNP, PCT and APHCHE Ⅱscore in patients of bloodstream infection(r=0.503, 0.548, 0.781,all P<0.05). The levels of suPAR, BNP, PCT and APACHE Ⅱ in the patients of blood stream infection were related to significant the prognosis (P<0.05). And these indexes can provide good evaluation on the prognosis of the patients. Conclusion Detection of serum suPAR, BNP can evaluate the severity of bloodstream infection and preliminarily determine the prognosis of patients with bloodstream infection. Therefore, the method is worth applying in the clinical field. Key words: Bloodstream infection; Soluble urokinase plasminogen activator receptor; Brain natriuretic peptide; APACHE Ⅱ score