Changes In N-terminal Pro-brain Natriuretic Peptide Research Articles

N-terminal Pro-B-Type Natriuretic Peptide and Malnutrition in Patients on Hemodialysis.

Natriuretic peptides, brain natriuretic peptide (BNP), and N-terminal probrain natriuretic peptide (NT-proBNP) are mainly known as diagnostic markers for heart failure with high diagnostic and prognostic values in the general population. In patients who are undergoing hemodialysis (HD), changes in NT-proBNP can be related to noncardiac problems such as fluid overload, inflammation, or malnutrition and can also be influenced by the dialysis characteristics. The current review aimed to summarize findings from studies on the association between NT-proBNP and malnutrition in HD patients. Articles published after 2009 and over a ten-year period were considered for inclusion. We first briefly discuss the traditional functions of NT-proBNP, and after, we describe the functions of this prohormone by focusing on its relation with protein energy wasting (PEW) in HD patients. Mechanisms that could explain these relationships were also discussed. Overall, 7 studies in which the investigation of the relations between NT-proBNP and nutritional status in HD patients were among the main objects were taken into account. NT-proBNP levels correlated with several factors described in the 4 categories of markers indicative of PEW (body mass and composition, muscle mass, biochemical criteria, and dietary intakes) and/or were associated with PEW. Interactions between several parameters could be involved in the association between NT-proBNP and malnutrition with a strong role of weight status. NT-proBNP is elevated in HD patients and is associated with malnutrition. Nevertheless, the prognostic value of NT-proBNP on nutritional status should be evaluated.

Diagnostic Utility of N-terminal pro-Brain Natriuretic Peptide and C-reactive Protein in Diagnosing Heart Failure in Patients with Acute Hypoxemic Respiratory Failure.

IntroductionShortness of breath is a leading cause of intensive care unit (ICU) admissions and is multifactorial. Acute hypoxemic respiratory failure due to heart failure is one of the leading causes of ICU admissions. N-terminal pro-brain natriuretic peptide (NT-proBNP) is secreted by ventricles and carries a negative predictive value for heart failure (2). NT-proBNP can also be raised in sepsis (4). Changes in NT-proBNP strongly correlated with changes in C-reactive protein (CRP) and leukocytes levels (8).ObjectiveThis study was conducted to explore the diagnostic utility of NT-proBNP and CRP to diagnose heart failure in patients presenting with acute hypoxemic respiratory failure.Materials and methodsAfter informed consent and approval from the institutional review board (IRB), patients of acute hypoxemic respiratory failure were included in the study. History and physical examination were done by a medical resident and recorded in the patients' files. Data were transferred to a structured proforma by the researcher. All tests were conducted within three hours of presentation. The diagnosis of heart failure was made by a panel of experts, including the consultant cardiologist and consultant intensivist in charge. The chest X-ray was reported by the radiologist. The cost of the test was afforded by the institution.Data were analyzed by SPSS version 15 (SPSS Inc., Chicago, Illinois). Analysis of variance (ANOVA), Pearson correlation and linear regression were applied to find out the relation between variables and significance.ResultsWe studied 137 patients. Out of them, 72.9% were diagnosed as heart failure. Heart failure was more common in females (43.7%) as compared to males (29%). NT-proBNP was raised in 111 (81%) patients and out of them, 88 patients (79%) had heart failure. Sensitivity and specificity of NT-proBNP were found to be (95.56%) and (46.81%), respectively. Similarly, CRP was 90% sensitive and 25.53% specific for heart failure. The most common findings in chest X-rays of patients with heart failure were upper lobe diversion and enlarged cardiothoracic ratio (71%).ConclusionWe concluded our study as NT-proBNP is a highly sensitive test to diagnose heart failure in settings of acute hypoxemic respiratory failure. CRP is also significantly raised in heart failure. Upper lobe diversion and an increased cardiothoracic ratio is a strong predictor of heart failure.

Randomized, double-blind, placebo-controlled, multicentre pilot study on the effects of empagliflozin on clinical outcomes in patients with acute decompensated heart failure (EMPA-RESPONSE-AHF).

Inhibition of sodium-glucose co-transporter 2 (SGLT2) reduces the risk of death and heart failure (HF) admissions in patients with chronic HF. However, safety and clinical efficacy of SGLT2 inhibitors in patients with acute decompensated HF are unknown. In this randomized, placebo-controlled, double-blind, parallel group, multicentre pilot study, we randomized 80 acute HF patients with and without diabetes to either empagliflozin 10mg/day or placebo for 30 days. The primary outcomes were change in visual analogue scale (VAS) dyspnoea score, diuretic response (weight change per 40 mg furosemide), change in N-terminal pro brain natriuretic peptide (NT-proBNP), and length of stay. Secondary outcomes included safety and clinical endpoints. Mean age was 76 years, 33% were female, 47% had de novo HF and median NT-proBNP was 5236 pg/mL. No difference was observed in VAS dyspnoea score, diuretic response, length of stay, or change in NT-proBNP between empagliflozin and placebo. Empagliflozin reduced a combined endpoint of in-hospital worsening HF, rehospitalization for HF or death at 60 days compared with placebo [4 (10%) vs. 13 (33%); P=0.014]. Urinary output up until day 4 was significantly greater with empagliflozin vs. placebo [difference 3449 (95% confidence interval 578-6321) mL; P < 0.01]. Empagliflozin was safe, well tolerated, and had no adverse effects on blood pressure or renal function. In patients with acute HF, treatment with empagliflozin had no effect on change in VAS dyspnoea, diuretic response, NT-proBNP, and length of hospital stay, but was safe, increased urinary output and reduced a combined endpoint of worsening HF, rehospitalization for HF or death at 60 days.

Relation of IGF-I with subclinical cardiovascular markers including intima-media thickness, left ventricular mass index and NT-proBNP.

Several studies revealed relations between low or high insulin-like growth factor I (IGF-I) levels and risk of cardiovascular diseases or mortality, whereas the mechanisms behind these associations are still unknown. The study aimed to explore the relations between IGF-I and changes in surrogate markers of cardiovascular disease including carotid intima-media thickness (IMT), left ventricular mass index (LVMI) and N-terminal pro-brain natriuretic peptide (NT-proBNP). Longitudinal data of the population-based cohort Study of Health in Pomerania (SHIP) were used. IMT was measured by ultrasonography and LVMI was determined based on echocardiography. IGF-I and IGF-binding protein-3 (IGFBP-3) levels were measured by chemiluminescent immunoassays and the IGF-I/IGFBP-3 ratio was calculated. Mixed linear regression models adjusted for known cardiovascular confounders were performed. Statistical analyses demonstrated relations between low baseline IGF-I levels (beta for ΔIMT per s.d. increase -0.044 (s.e. 0.012)) or IGF-I/IGFBP-3 ratio (beta -0.045 (0.012)) and a long-term IMT increase. No associations between IGF-I, IGFBP-3 or IGF-I/IGFBP-3 ratio and changes in LVMI were detected. With respect to NT-proBNP sex-specific associations with IGF-I were found. In women, higher baseline IGF-I levels (beta for ΔNT-proBNP per s.d. increase 5.92 (2.2)) or IGF-I/IGFBP-3 ratio (beta 4.48 (2.2)) were related to an increase in NT-proBNP levels. Among men, U-shaped relations of baseline levels of IGF-I, IGFBP-3 and the IGF-I/IGFBP-3 ratio with an increase in NT-proBNP were found. The study detected significant relations between IGF-I and long-term changes in IMT and NT-proBNP but not LVMI. These findings argue for different effects of the IGF-I axis with respect to various cardiovascular entities.

Possible Mechanisms Underlying Elevated Serum N-Terminal Pro-Brain Natriuretic Peptide in Healthy Japanese Subjects.

Background: The precise mechanisms underlying elevation of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) in healthy subjects have not been fully clarified.Methods and Results: In 2,844 Japanese healthy subjects with serum NT-proBNP <125 pg/mL, (1) brachial-ankle pulse wave velocity and (2) second peak of the peripheral systolic blood pressure minus diastolic blood pressure (pulse pressure 2 [PP2]), as markers of cardiac afterload; (3) fibrosis 4 score (FIB-4 score, a marker of liver fibrosis), as a marker of cardiac preload; and (4) ratio of the pre-ejection time to ejection time (PEP/ET), as a marker of cardiac systolic function, were measured. At the first examination, after the adjustments, log-transformed serum NT-proBNP was associated with PP2 and FIB-4 score, but not with PEP/ET. These parameters were successfully measured again after a 3-year interval in 1,978 subjects. On Pearson’s correlation analysis, change in PP2 and FIB-4 score during the study period was significantly correlated with change in serum NT-proBNP (r=0.05, 0.09, respectively; P<0.01).Conclusions: In apparently healthy Japanese subjects, both increased cardiac preload and increased cardiac afterload, but not impaired cardiac systolic function, may be associated with elevated serum NT-proBNP.

Effects of a Higher Heart Rate on Quality of Life and Functional Capacity in Patients With Left Ventricular Diastolic Dysfunction

There is no evidence-based treatment for heart failure with preserved ejection fraction. Although lower heart rates (HRs) provide an unequivocal benefit for patients with HF with reduced ejection fraction, higher HR might convey important hemodynamic and substrate-modifying benefits in patients with diastolic dysfunction. In a prospective study of 20 stable outpatients with diastolic dysfunction and pacemakers, we evaluated the effects of a 4-week increase in the lower pacemaker rate to 80 beats/min followed by reversal to the previous lower HR setting from weeks 4 to 6. We assessed quality of life (Minnesota Living with Heart Failure Questionnaire), 6-minute walk test and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Pacing at 80 beats/min significantly improved quality of life and the 6-minute walk test (p ≤0.05). There was a strong positive correlation between the pacing-induced changes in NT-proBNP and baseline QRS intervals (r2 = 0.31, p <0.01). Stratification by QRS duration revealed that pacing at 80 beats/min led to -21 ± 26% reduction in NT-proBNP in patients with QRS ≤150 ms, whereas QRS >150 ms was associated with a 26 ± 35% increase in NT-proBNP (p <0.01). Patients physiologically paced from the conduction system had a -46 ± 26% reduction in NT-proBNP at 80 beats/min as compared with 4 ± 26% and 13 ± 26% change with pacing from the right atrial appendage and right ventricular apical septum (pinteraction = 0.04). In conclusion, increasing the lower rate setting of pacemakers to 80 beats/min in patients with diastolic dysfunction improves quality of life, functional capacity, and NT-proBNP for those patients with a baseline QRS ≤150 ms. These findings suggest that higher HRs may provide meaningful benefits to patients with left ventricular diastolic dysfunction and heart failure with preserved ejection fraction.

Sex and regional differences in myocardial plasticity in aortic stenosis are revealed by 3D model machine learning.

Left ventricular hypertrophy (LVH) in aortic stenosis (AS) varies widely before and after aortic valve replacement (AVR), and deeper phenotyping beyond traditional global measures may improve risk stratification. We hypothesized that machine learning derived 3D LV models may provide a more sensitive assessment of remodelling and sex-related differences in AS than conventional measurements. One hundred and sixteen patients with severe, symptomatic AS (54% male, 70 ± 10 years) underwent cardiovascular magnetic resonance pre-AVR and 1 year post-AVR. Computational analysis produced co-registered 3D models of wall thickness, which were compared with 40 propensity-matched healthy controls. Preoperative regional wall thickness and post-operative percentage wall thickness regression were analysed, stratified by sex. AS hypertrophy and regression post-AVR was non-uniform-greatest in the septum with more pronounced changes in males than females (wall thickness regression: -13 ± 3.6 vs. -6 ± 1.9%, respectively, P < 0.05). Even patients without LVH (16% with normal indexed LV mass, 79% female) had greater septal and inferior wall thickness compared with controls (8.8 ± 1.6 vs. 6.6 ± 1.2 mm, P < 0.05), which regressed post-AVR. These differences were not detectable by global measures of remodelling. Changes to clinical parameters post-AVR were also greater in males: N-terminal pro-brain natriuretic peptide (NT-proBNP) [-37 (interquartile range -88 to -2) vs. -1 (-24 to 11) ng/L, P = 0.008], and systolic blood pressure (12.9 ± 23 vs. 2.1 ± 17 mmHg, P = 0.009), with changes in NT-proBNP correlating with percentage LV mass regression in males only (ß 0.32, P = 0.02). In patients with severe AS, including those without overt LVH, LV remodelling is most plastic in the septum, and greater in males, both pre-AVR and post-AVR. Three-dimensional machine learning is more sensitive than conventional analysis to these changes, potentially enhancing risk stratification. Regression of myocardial fibrosis after aortic valve replacement (RELIEF-AS); NCT02174471. https://clinicaltrials.gov/ct2/show/NCT02174471.

Empagliflozin in heart failure patients with reduced ejection fraction: a randomized clinical trial (Empire HF)

BackgroundData from recent cardiovascular outcome trials in patients with type 2 diabetes (T2D) suggest that sodium-glucose cotransporter 2 (SGLT2) inhibitors can prevent development of heart failure (HF) and prolong life in patients without HF. Ongoing event-driven trials are investigating whether the same effect is present in patients with well-defined HF. The mechanism behind the effect of SGLT2 inhibitors in patients with T2D and the potential effect in patients with overt HF is presently unknown.MethodsThis is a randomized, double-blinded, placebo-controlled, parallel group, clinical trial including HF patients with reduced left ventricular ejection fraction (HFrEF) with an ejection fraction ≤ 40% on optimal therapy recruited from specialized HF clinics in Denmark. The primary aim is to investigate the effect of the SGLT2 inhibitor empagliflozin on N-terminal pro-brain natriuretic peptide (NT-proBNP). Secondary endpoints include cardiac biomarkers, function and hemodynamics, metabolic and renal parameters, daily activity level, and quality of life. Patients are assigned 1:1 to 90 days treatment with empagliflozin 10 mg daily or placebo. Patients with T2D are required to be on recommended doses of anti-glycemic therapy with a hemoglobin A1c (HbA1c) of 6.5–10.0% (48–86 mmol/mol). To show a between-group difference in the change of NT-proBNP of 30%, a total of 189 patients will be included.DiscussionThe Empire HF trial will elucidate the effects and modes of action of empagliflozin in HFrEF patients with and without T2D and provide important mechanistic data which will complement ongoing event-driven trials.Trial registrationClinicaltrialsregister.eu, EudraCT Number 2017-001341-27. Registered on 29 May 2017.ClinicalTrials.gov, NCT03198585. Registered on 26 June 2017.

Abstract P046: Sex Hormone Levels and 10-Year Change in N-Terminal Pro-Brain Natriuretic Peptide Among Men and Post-Menopausal Women: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background: The risk of cardiovascular disease (CVD) differs between men and women, and sex hormones are thought to play a key role. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive biomarker of ventricular wall stress and a strong predictor of incident cardiovascular disease (CVD) and heart failure (HF). It can thus be seen as an early marker of CVD. We evaluated whether sex hormones levels were associated with change in NT-proBNP concentrations over 10 years in MESA. Methods: We studied 2348 men and 2041 post-menopausal women. Serum testosterone (T), estradiol, dehydroepiandrosterone (DHEA), and sex hormone binding globulin (SHBG) were measured at Exam 1 (2000-02); free T and bioavailable T were calculated. NT-proBNP was measured by Roche assay at Exam 1, plus Exam 3 (2004-05) and/or Exam 5 (2010-12). Multivariable-adjusted linear mixed effects models were used to study associations between sex hormone levels and change in NT-proBNP over an approximately 10-year period. Results: Mean (SD) age (years) at baseline was 65 (9) for women and 62 (10) for men. Women had higher NT-proBNP than men (median 76.6 vs 37.1 pg/ml). Among women, after adjusting for demographic, socioeconomic, and CVD risk factors, higher total T, bioavailable T, and free T were independently associated with a greater increase in NT-proBNP over 10 years, whereas estradiol and SHBG were inversely associated with change in NT-proBNP ( Table ). When sex hormones were analyzed together in the same model, total T was positively associated and SHBG was inversely associated with change in NT-proBNP. In men, higher estradiol was associated with greater 10-year increase in NT-proBNP. These associations were preserved after excluding individuals with ejection fraction &lt;50%. Conclusion: A more androgenic sex hormone profile in post-menopausal women and a more estrogenic profile in men were independently associated with 10-year change in NT-proBNP levels. Sex hormone patterns may thus explain in part sex differences in the development of CVD and HF.

Pharmacodynamic modeling of cardiac biomarkers in breast cancer patients treated with anthracycline and trastuzumab regimens

Trastuzumab is associated with cardiotoxicity, manifesting as a decrease of the left-ventricular ejection fraction (LVEF). Administration of anthracyclines prior to trastuzumab increases risk of cardiotoxicity. High-sensitive troponin T and N-terminal-pro-brain natriuretic peptide (NT-proBNP) are molecular markers that may allow earlier detection of drug-induced cardiotoxicity. In this analysis we aimed to quantify the kinetics and exposure–response relationships of LVEF, troponin T and NT-proBNP measurements, in patients receiving anthracycline and trastuzumab. Repeated measurements of LVEF, troponin T and NT-proBNP and dosing records of anthracyclines and trastuzumab were available from a previously published clinical trial. This trial included 206 evaluable patients with early breast cancer. Exposure to anthracycline and trastuzumab was simulated based on available dosing records and by using a kinetic-pharmacodynamic (K-PD) and a fixed pharmacokinetic (PK) model from literature, respectively. The change from baseline troponin T was described with a direct effect model, affected by simulated anthracycline concentrations, representing myocyte damage. The relationship between trastuzumab and LVEF was described by an indirect effect compartment model. The EC50 for LVEF decline was significantly affected by the maximum troponin T concentration after anthracycline treatment, explaining 15.1% of inter-individual variability. In this cohort, NT-proBNP changes could not be demonstrated to be related to anthracycline or trastuzumab treatment. Pharmacodynamic models for troponin T and LVEF were successfully developed, identifying maximum troponin T concentration after anthracycline treatment as a significant determinant for trastuzumab-induced LVEF decline. These models can help identify patients at risk of drug-induced cardiotoxicity and optimize cardiac monitoring strategies.

Plasma N-terminal pro-brain natriuretic peptide concentrations before and after pericardiocentesis in dogs with cardiac tamponade secondary to spontaneous pericardial effusion

ObjectiveTo determine if concentrations of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) are increased in dogs with cardiac tamponade and if there is a significant increase in plasma NT-proBNP after pericardiocentesis. AnimalsTen client-owned dogs with spontaneous cardiac tamponade. MethodsProspective clinical study. Cardiac tamponade was suspected from physical examination and confirmed with echocardiography. Blood was collected and plasma NT-proBNP concentrations were measured before and 30–60 min following pericardiocentesis and resolution of cardiac tamponade. Within-subject changes in plasma NT-proBNP were compared by the Wilcoxon signed-rank test. ResultsThe plasma NT-proBNP concentrations measured within the reference interval in seven of 10 dogs before pericardiocentesis and in six of 10 dogs following pericardiocentesis. Following pericardiocentesis, there was a statistically significant increase in median NT-proBNP concentration (733 pmol/L, range 250–3,297) compared with the values measured before (643 pmol/L, range 250–3,210, P = 0.004). The NT-proBNP concentration increased in 90% of the dogs following pericardiocentesis. ConclusionsAn upper reference limit of 900 pmol/L for plasma NT-proBNP is insensitive for the diagnosis of pericardial effusion and cardiac tamponade in dogs. Plasma NT-proBNP concentration commonly increases following pericardiocentesis, perhaps related to improved ventricular filling and stretch.

Biologic variability of N-terminal pro-brain natriuretic peptide in healthy dogs and dogs with myxomatous mitral valve disease

IntroductionTo determine the biologic variability of N-terminal pro-brain natriuretic peptide (NTproBNP) in healthy dogs and dogs with various stages of myxomatous mitral valve disease (MMVD). AnimalsThirty-eight privately owned dogs: 28 with MMVD and 10 healthy controls. Materials and methodsProspective clinical study with comprehensive evaluation used to group dogs as healthy or into three stages of MMVD based on current guidelines. NTproBNP was measured hourly, daily, and weekly. For each group, analytical (CVA), within-subject (CVI), and between-subject (CVG) coefficients of variability were calculated in addition to percent critical change value (CCV) and index of individuality (IoI). ResultsFor healthy dogs, calculated NTproBNP values were: CVA = 4.2%; CVI = 25.2%; CVG = 49.3%; IoI = 0.52, and CCV = 70.8%. For dogs with MMVD, calculated NTproBNP values were: CVA = 6.2%; CVI = 20.0%; CVG = 61.3%; IoI = 0.34, and CCV = 58.2%. ConclusionsBiologic variability affects NTproBNP concentrations in healthy dogs and dogs with MMVD. Monitoring serial individual changes in NTproBNP may be clinically relevant in addition to using population-based reference ranges to determine changes in disease status.

N-terminal pro-B-type natriuretic peptide-guided therapy in patients hospitalized for acute heart failure.

In patients with acute heart failure, high levels of N-terminal-pro-brain natriuretic peptide (NT-proBNP) at discharge are associated with worse outcomes. We hypothesized that NT-proBNP-guided therapy may improve prognosis. Two hundred and seventy-one consecutive patients, admitted for acute heart failure, were prospectively randomized to NT-proBNP-guided therapy or control group. The NT-proBNP-guided therapy group underwent medical treatment intensification when predischarge NT-proBNP was at least 3000 pg/ml. The primary endpoint was cardiovascular death or cardiovascular rehospitalization at day 182. The secondary endpoints were all-cause death, cardiovascular death, cardiovascular rehospitalization, heart failure rehospitalization, and cardiovascular death or heart failure rehospitalization at day 182. Treatment intensification in the NT-proBNP-guided therapy group regarded mainly diuretics. The NT-proBNP strategy was not associated with a significant reduction of the primary endpoint [43% intervention vs. 39% controls, hazard ratio 1.22 (0.84, 1.76), P = 0.305] and of any secondary endpoint. The change of NT-proBNP from predischarge to discharge was associated with the risk of cardiovascular death or cardiovascular rehospitalization through day 182, even after multivariable adjustment. NT-proBNP-guided therapy resulted mainly in an increase of diuretics in acute setting and compared with clinical evaluation alone did not improve prognosis. However, the reduction of NT-proBNP at discharge was an independent predictor of outcomes.

Improvement in insulin resistance is greater when infliximab is added to methotrexate during intensive treatment of early rheumatoid arthritis-results from the IDEA study.

To determine the change in established biomarkers of cardiovascular (CV) risk, namely, total cholesterol/high-density lipoprotein cholesterol ratio (TC/HDL-C), N-terminal pro-brain natriuretic peptide (NT-proBNP) and insulin resistance (IR) in patients with early RA treated with two different treat-to-target strategies. Fasting glucose, lipids, insulin and NT-proBNP were measured at baseline, weeks 26 and 78 in 79 DMARD-naïve RA patients, free of CV disease, as part of a double-blind randomized controlled trial of MTX with either infliximab (IFX) or methylprednisolone as induction therapy. Homeostasis model assessment-estimated IR (HOMA-IR) (glucose*insulin/405) was used to measure IR. Multiple imputation was employed, and linear regression analyses were adjusted for baseline values. Changes in DAS44-CRP did not differ between the treatment arms at weeks 26 and 78. Mean TC/HDL-C, HOMA-IR and NT-proBNP improved in both groups at weeks 26 and 78, although change in NT-proBNP was not statistically significant at week 78. Changes in TC/HDL-C and NT-proBNP were similar between treatment arms, but HOMA-IR values in the IFX + MTX arm were 42% lower than those treated with MTX + methylprednisolone at week 78 (P = 0.003); the difference remained significant after adjustment for baseline BMI, ACPA positivity, smoking status and intramuscular glucocorticoid use (P = 0.007). When implementing a treat-to-target approach, treatment of early RA was associated with improvement in TC/HDL-C, HOMA-IR and NT-proBNP, and a greater long-term improvement in HOMA-IR was seen in those treated with IFX. EU Clinical Trials Register, http://www.clinicaltrialsregister.eu, Eudract-2005-005013-37; ISRTCNregisrty, http://www.isrctn.com, ISRCTN48638981.

Analyzing Dynamic Changes of Laboratory Indexes in Patients with Acute Heart Failure Based on Retrospective Study.

Background. Changes of N-terminal probrain natriuretic peptide (NT-proBNP) have been studied whether in the long term or the short term in patients of acute heart failure (AHF); however, changes of NT-proBNP in the first five days and their association with other factors have not been investigated. Aims. To describe the dynamic changes of relevant laboratory indexes in the first five days between different outcomes of AHF patients and their associations. Methods and Results. 284 AHF with dynamic values recorded were analyzed. Changes of NT-proBNP, troponin T, and C-reactive protein were different between patients with different outcomes, with higher values in adverse group than in control group at the same time points (p < 0.05). Then, prognostic use and risk stratification of NT-proBNP were assessed by receiver-operating characteristic curve and logistic regression. NT-proBNP levels at day 3 showed the best prognostic power (area under the curve = 0.730, 95% confidence interval (CI): 0.657 to 0.794) and was an independent risk factor for adverse outcome (odds ratio, OR: 2.185, 95% CI: 1.584–3.015). Classified changes of NT-proBNP may be predictive for adverse outcomes in AHF patients. Conclusions. Sequential monitoring of laboratory indexes within the first 5 days may be helpful for management of AHF patients.

Abstract 12849: Changes in N-terminal Pro Brain Natriuretic Peptide Levels Predicts Mortality and Heart Failure Hospitalization in Patients With Heart Failure and Preserved Ejection Fraction

Introduction: Changes in N-terminal pro brain natriuretic peptide (NT-proBNP) have been demonstrated to correlate with outcomes in patients with heart failure (HF) and reduced ejection fraction (EF). However the prognostic value of a change in NT-proBNP in patients with heart failure and preserved ejection fraction (HFPEF) is unknown. Hypothesis: To assess the impact of changes in NT-proBNP on all-cause mortality, HF hospitalization and their composite in an unselected population of patients with HFPEF. Methods: 643 outpatients (age 72+12 years; 41% females) with HFPEF (ejection fraction ≥40%) enrolled in the Swedish Heart Failure Registry between 2005 and 2012 and reporting NT-proBNP levels assessment at initial registration and at follow-up were prospectively studied. Patients were divided into 2 groups according the median value of NT-proBNP absolute change that was 0 pg/ml. Median follow-up from first measurement was 2.25 years (IQR: 1.43 to 3.81). Adjusted Cox’s regression models were performed using total mortality, HF hospitalization (with censoring at death) and their composite as outcomes. Results: After adjustments for 19 baseline variables including baseline NT-proBNP, as compared with an increase in NT-proBNP levels at 6 months (NT-proBNP change&gt;0 pg/ml), a reduction in NT-proBNP levels (NT-proBNP change&lt;0 pg/ml) was associated with a 45.2% reduction in risk of all-cause death (HR: 0.548; 95% CI: 0.378 to 0.796; p:0.002), a 50.1% reduction in risk of HF hospitalization (HR: 0.49; 95% CI: 0.362 to 0.689; p&lt;0.001) and a 42.6% reduction in risk of the composite outcome (HR: 0.574; 95% CI: 0.435 to 0.758; p&lt;0.001)(Figure). Conclusions: Reductions in NT-proBNP levels over time are independently associated with an improved prognosis in HFPEF patients. Changes in NT-proBNP could represent a surrogate outcome in phase 2 HFPEF trials.

Adding point of care ultrasound to assess volume status in heart failure patients in a nurse-led outpatient clinic. A randomised study

ObjectivesMedical history, physical examination and laboratory testing are not optimal for the assessment of volume status in heart failure (HF) patients. We aimed to study the clinical influence of focused...

Early Trends in N-Terminal Pro–Brain Natriuretic Peptide Values After Left Ventricular Assist Device Implantation for Chronic Heart Failure

Left ventricular assist devices (LVADs) acutely decrease left ventricular wall stress. Thus, early postoperative levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) should decrease. This study investigated postoperative changes in NT-proBNP levels, the parameters related to changes, and the possible association with complications by performing a retrospective analysis of changes in daily NT-proBNP (pg/ml) levels from admission to discharge both before and after LVAD implantation in a tertiary referral center. For 72 patients implanted with HeartMate II LVADs, baseline NT-proBNP levels were elevated at 3,943 ng/ml (interquartile range 1,956 to 12,964). Preoperative stabilization led to marked decreases in NT-proBNP. Levels peaked 3 days after surgery and subsequently decreased. Patients with complicated postoperative courses had higher early postoperative elevations. By discharge, NT-proBNP decreased markedly but was still 2.83 (1.60 to 5.76) times the age-based upper limit of normal. The 26% reduction in NT-proBNP between admission and discharge was due mostly to the preoperative reductions and not those induced by the LVAD itself. The decrease was not associated with decreases in LV volume. In conclusion, preoperative treatment reduces NT-proBNP values. The magnitude of early postoperative changes is related to the clinical course. Levels at discharge remain markedly elevated and similar to values after preoperative stabilization despite presumptive acute LV unloading.

Determinants of N-Terminal Pro-Brain Natriuretic Peptide Variation in Hemodialysis Patients and Prediction of Survival

Background/Aims: N-Terminal pro-brain natriuretic peptide (NT-proBNP) is a predictor of cardiac events and death in the general population and in chronic kidney disease. There is limited information on how natriuretic peptides vary in dialysis patients. The aim of this study was to analyze NT-proBNP variability, factors predicting its variability and survival related to NT-proBNP variability. Methods: A prospective 3-month observational study of prevalent hemodialysis patients with monthly measurements of NT-proBNP was carried out. A total of 211 hemodialysis patients were included, and mortality was recorded during 52 months of follow-up. Results: Inflammation was the strongest predictor of NT-proBNP variability. Patients with constantly high NT-proBNP had an increased risk of death adjusting for age, sex, dialysis vintage and comorbidity but not when also adjusting for nutritional status. Conclusions: Longitudinal changes in NT-proBNP are associated with changes in inflammation, nutritional status, age and comorbidity. Due to strong interactions with predictors of mortality such as nutritional status, we were unable to confirm NT-proBNP as an independent marker for mortality in dialysis patients.

Independence of the blood pressure lowering effect and efficacy of the angiotensin receptor neprilysin inhibitor, LCZ696, in patients with heart failure with preserved ejection fraction: an analysis of the PARAMOUNT trial

The first in class angiotensin receptor neprilysin inhibitor, LCZ696 has been shown to reduce levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), reduce left atrial size and improve New York Heart Association (NYHA) class in patients with heart failure with preserved ejection fraction (HFpEF). We examined whether the effects of LCZ696 were independent of systolic blood pressure (SBP) lowering. In the Prospective comparison of ARNi (angiotensin receptor neprilysin inhibitor) with ARB (angiotensin receptor blocker) on Management Of heart failUre with preserved ejectioN fracTion (PARAMOUNT) trial 301 patients were randomly assigned to LCZ696 or valsartan. We examined the relationship between SBP lowering and LCZ696 on NT-proBNP level, left atrial size, NYHA class and estimated glomerular filtration rate (eGFR). By 12 weeks blood pressure was reduced by 9 mmHg (SD 15)/5 mmHg (SD 11) in patients receiving LCZ696 in comparison with 3 mmHg (SD 17)/2 mmHg (SD 12) in those receiving valsartan. The change in NT-proBNP was poorly correlated with change in SBP (LCZ696, r = 0.17, P = 0.06; valsartan, r = 0.05, P = 0.58) After adjustment for change in SBP, the ratio of change in NT-proBNP at 12 weeks for LCZ696 vs. valsartan was 0.76 (95% CI 0.63-0.93, P = 0.008), and similar to the ratio not adjusting for SBP (0.76, 95% CI 0.63-0.92, P = 0.006); P for interaction was 0.38). Similarly, reduction in left atrial volume index at 36 weeks, improvement in NYHA class and eGFR were all independent of the change in SBP. In patients with HFpEF, the effect of the angiotensin receptor neprilysin inhibitor LCZ696 on NT-proBNP, left atrial volume, functional class, and eGFR was independent of reduction in SBP.