Changes In NT-proBNP Research Articles

Prediction of clinical outcome in patients treated with cardiac resynchronization therapy - the role of NT-ProBNP and a combined response score

BackgroundCardiac resynchronization therapy (CRT) is an established therapy for appropriately selected patients with heart failure. Response to CRT has been heterogeneously defined using both clinical and echocardiographic measures, with poor correlation between the two.MethodsThe study cohort was comprised of 202 CRT-treated patients and CRT response was defined at 6 months post-implant. Echocardiographic response (E+) was defined as a reduction in LVESV ≥ 15%, clinical response as an improvement of ≥ 1 NYHA class (C+), and biomarker response as a ≥ 25% reduction in NT-proBNP(B+). The association of response measures (E+, B+, C+; response score range 0–3) and clinical endpoints at 3 years was assessed in landmarked Cox models.ResultsEcho and clinical responders demonstrated greater declines in NT-proBNP than non-responders (median [E+/B+]: -52%, [E+]: -27%, [C+]: -39% and [E-/C-]: -13%; p = 0.01 for trend). Biomarker (HR 0.43 [95% CI: 0.22–0.86], p = 0.02) and clinical (HR 0.40 [0.23–0.70] p = 0.001) response were associated with a significantly reduced risk of the primary endpoint. When integrating each response measure into a composite score, each 1 point increase was associated with a 31% decreased risk for a composite endpoint of mortality, LVAD, transplant and HF hospitalization (HR 0.69 [95% CI: 0.50–0.96], p = 0.03), and a 52% decreased risk of all-cause mortality (HR 0.48 [95% CI: 0.26–0.89], p = 0.02).ConclusionSerial changes in NT-proBNP are associated with clinical outcomes following CRT implant. Integration of biomarker, clinical, and echocardiographic response may discriminate CRT responders versus non-responders in a clinically meaningful way, and with higher accuracy.Trial registrationThe cohort was combined from study NCT01949246 and the study based on local review board approval 2011/550 in Lund, Sweden.

Systemic inflammation and functional capacity in elderly heart failure patients.

Elevated C-reactive protein (CRP) is associated with adverse outcomes in heart failure (HF) patients. Beta-blocker therapy may lower CRP levels. To assess if the changes of high-sensitivity (hs) CRP levels in HF patients over 12-week titration with beta-blockers correlate with functional capacity, plasma hs-CRP levels were measured in 488 HF patients [72.1 ± 5.31years, LVEF 40% (33/50)]. Hs-CRP, NT-proBNP and 6-min-walk-test (6MWT) were assessed at baseline and at week 12. Patients were divided based on hs-CRP changes (cut-off > 0.3mg/dl) into low-low (N = 225), high-high (N = 132), low-high (N = 54), high-low (N = 77) groups. At baseline, median hs-CRP concentration was 0.25 (0.12/0.53)mg/dl, NT-proBNP 551 (235/1455)pg/ml and average 6MWT distance 334 ± 105m. NT-proBNP changes were significantly different between the four hs-CRP groups (P = 0.011). NT-proBNP increased in the low-high group by 30 (- 14/88)pg/ml and decreased in the high-low group by - 8 (- 42/32)pg/ml. 6MWT changes significantly differed between groups [P = 0.002; decrease in the low-high group (- 18 ± 90m) and improvement in the low-low group (24 ± 62m)]. After beta-blocker treatment, hs-CRP levels are associated with functional capacity in HF patients. Whether this represents a potential target for intervention needs further study.

ANALYSIS OF CHANGE IN NT-proBNP AFTER ANGIOTENSIN RECEPTOR BLOCKER (ARB) THERAPY IN PATIENT WITH HEART FAILURE

NT-proBNP is an inactive fragment of BNP secreted by stretched ventricle as response to wall stress in patients with heart failure. As a specific cardiac marker, elevated NT-proBNP correlates well with heart failure severity. The principle of heart failure therapy is modulation on neurohormonal activation. ARB can modulate neurohormon on RAA system, that result in decreasing NT-proBNP level and favorable outcomes. Reduction in NT-proBNP more than biologic variability (> 25%) shows a therapy response.This study was to analyze change of NT-proBNP after ARB therapy in ambulatory HF patients. This observational prospective study was carried from September to December 2015. Blood sampling was performed on patients who meet the inclusion criteria of the study at first visit and after 2 months therapy. NT-proBNP was measured by IMMULITE® as primary parameter and creatinin as secondary parameter. There are 14 patients met the inclusion criteria of the study (11 males and 3 females). ARB therapy used in patients were Valsartan (64%), Telmisartan (22%) and Candesartan (14%). After 2 months ARB therapy, a decrease in level of NT-proBNP with initial median 3092.5 (216 – 32112) pg/ml to 2135.5 (350 – 16172) pg/ml respectively were statistically significant (p=0.003). And the secondary parameter creatinin serum convert to eGFR shows a change in eGFR with initial median 73.33 (37.05 – 266.68) ml/minute to 81.04 (39.31 – 167.02) ml/minute respectively were statistically not significant (p=0.657). There were 7 patients (50%) have a decrease > 25%. In this study, we found that ARB therapy can change NT-proBNP level significantly after 2 months therapy.

Effect of phosphodiesterase-5 inhibition with Tadalafil on SystEmic Right VEntricular size and function – A multi-center, double-blind, randomized, placebo-controlled clinical trial – SERVE trial - Rational and design

BackgroundPatients with a systemic right ventricle (RV) have a compromised late outcome caused by ventricular dysfunction. Standard medical heart failure therapy has not been shown to improve RV function and survival in these patients. Phosphodiesterase (PDE)-5 inhibition increases contractility in experimental models of RV hypertrophy, but not in the normal RV. In clinical practice, the effects of PDE-5 inhibition on systemic RV function and exercise capacity in adults with a systemic RV have not been tested. MethodsThe SERVE protocol is a double-blind, randomized placebo-controlled multicenter superiority trial to study the effect of PDE-5 inhibition with Tadalafil on RV volumes and function in patients with either D-transposition of the great arteries repaired with an atrial switch procedure or with congenitally corrected transposition of the great arteries. Tadalafil 20mg or placebo will be given over a study period of 3years. The primary endpoint is the change in mean end-systolic RV volumes from baseline to study end at 3years of follow-up (or at the time of permanent discontinuation of the randomized treatment if stopped before 3- years of follow-up), and will be measured by cardiovascular magnetic resonance imaging (CMR) or by cardiac computed tomography in patients with contraindications for CMR. Secondary endpoints are changes in RV ejection fraction, VO2max and NT-proBNP. ConclusionThe objective of this study is to assess the effect of PDE-5 inhibition with Tadalafil on RV size and function, exercise capacity and neurohumoral activation in adults with a systemic RV over a 3-year follow-up period.

The clinical efficacy of Xinmailong on heart failure in coronary heart disease and on the levels of hs-C-reactive protein and N-terminal B-type natriuretic peptide

Objective To investigate the clinical efficacy of Xinmailong on heart failure in coronary heart disease and on the levels of hs-C-reactive protein(hs-CRP)and N-terminal B-type natriuretic peptide(NT-proBNP). Methods 84 elderly patients diagnosed with heart failure in coronary heart disease were enrolled in this study at our hospital from October 2014 to October 2015.All patients were randomly divided into the control group with conventional treatment(n=42)and observation group with conventional plus Xinmailong treatment(n=42). The Lee’s heart failure score, cardiac function grade, quality of life score and the changes of plasma hs-CRP and NT-proBNP after one week of therapy were compared between the two groups before versus after treatment.The adverse reactions were observed during the treatment. Results The clinical efficacy rate of heart failure after treatment was significantly higher in the observation group(83.3%, 35 cases)than in control group(54.7%, 23 cases)(χ2=8.016, P=0.033). The clinical efficacy of heart function after treatment was significantly higher in the observation group(80.9%, 34 cases)than in the control group(59.5%, 25 cases)(χ2=6.219, P=0.019). After treatment, the quality of life score was significantly lower in observation group(15.89±3.39)than in the control group(23.80±5.66)(t=7.266, P=0.026). The plasma levels of NT-proBNP and hs-CRP were significantly lower after than before treatment in NT-proBNP〔(1 136.6±236.8)ng/L and (2 266.9±260.9)ng/L〕, and in hs-CRP〔(3.06±0.26)mg/L and (3.56±0.29)mg/L〕(t=6.608、5.106, P=0.019、0.009). There were no serious adverse reactions in both groups during the treatment. Conclusions Xinmailong can not only improve safely and effectively the quality of life of patients, but also block the atherosclerosis of the inflammatory response. Key words: Heart failure; Natriuretic peptide, brain; C-reactive protein

April 2017 at a glance: cardiomyopathies and clinical trials

April 2017 at a glance: cardiomyopathies and clinical trials

Circulating Adiponectin Levels Following Treatment Can Predict Late Clinical Outcomes in Chronic Heart Failure.

Circulating adiponectin concentration increases in patients with chronic heart failure (HF). We sought to explore the prognostic value of temporal changes in adiponectin concentration following treatment for chronic HF. Serum adiponectin levels were measured at baseline and after a 3-month anti-failure treatment in 124 patients with symptomatic chronic systolic HF. Major adverse cardiac events (MACE) including death, heart transplantation, or hospitalization with worsening HF during a median follow-up period of 752 days were determined. Univariate and multivariate analysis showed that high levels of adiponectin after a 3-month treatment were associated with a 3.8-fold increased risk of MACE (p = 0.03), independent of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Moreover, the combining of circulating levels of adiponectin with NT-proBNP provided independent and additional prognostic value in identifying high risk patients with MACE during follow-up. Changes in adiponectin and NT-proBNP over time provide prognostic information. When adiponectin is used in conjunction with NT-proBNP in chronic HF, the prognostic value may be better than if each biomarker is used separately.

ПРЕДИКТОРЫ ДЛИТЕЛЬНОЙ ГОСПИТАЛИЗАЦИИ У ВЗРОСЛЫХ ПАЦИЕНТОВ С ПРИОБРЕТЕННЫМИ ПОРОКАМИ СЕРДЦА, ОПЕРИРОВАННЫХ В УСЛОВИЯХ ГИПОТЕРМИЧЕСКОГО И НОРМОТЕРМИЧЕСКОГО ИСКУССТВЕННОГО КРОВООБРАЩЕНИЯ

Goal of the study: to identify the predictors of continuous hospital stay in adult patients with acquired valvular disease, operated with hypothermic and normothermic cardiopulmonary bypass due definitive repair of the disease. Materials and methods: 140 patients who had surgical treatment of acquired valvular disease with the use of cardiopulmonary bypass were randomly divided into two similar groups where hypothermic and normothermic cardiopulmonary bypasses were used. Peri-operative concentration of NT-proBNP, clinical course of the post-operative period, hospital morbidly and mortality were assessed. Results. No confident difference was observed in the changes of NT-proBNP in the groups, what could provide the evidence of the similar effects of both hypothermic and normothermic cardiopulmonary bypasses on integrative functional rates of cardiovascular system. However it was noted that increase of NT-proBNP plasma concentration during first 24 hours after the surgery, as well as age, chronic obstructive pulmonary disease (COPD), maximum degree of chronic cardiac failure (CCF), duration of artificial pulmonary ventilation (APV), episodes of atrial fibrillation (AF) in the post-operative period were the predictors of continuous hospital stay Conclusion. The degree of the increase in post-operative level of NT-proBNP does not depend on the perfusion temperature. NT-proBNP plasma concentration during first 24 hours after the surgery, age, COPD, maximum degree of CCF, duration of APV, episodes of AF in the post-operative period are independent predictors of continuous hospital stay.

Exploring the relation between changes in NT-proBNP and renal function in patients with suspected heart failure using structural equation modelling

BackgroundThe relation between changes in NT-proBNP and renal function has commonly been studied using multiple regressions, which may ignore the complexity of relations between related variables. Methods and resultsData were collected from patients referred with suspected heart failure (HF) to a community service. Structural equation modelling (SEM) was used to assess the association between changes in NT-proBNP at 1year, and other pre-specified variables including age, sex, BMI, eGFR, loop diuretics and ACE inhibitor. Of 1006 patients with a follow-up NT-proBNP at 1year, 882 (88%) had HF. The baseline median age was 72 (IQR: 63–78) years, 732 (73%) were men, 668 (66%) had left ventricular systolic dysfunction and 769 (76%) had NT-proBNP>400pg/ml. For all patients at 1year, 243 (24%) patients had at least a 50% reduction in NT-proBNP, and 199 (20%) had at least a 50% increase, only 40 (3%) had <3% change. Change in NT-proBNP was strongly associated with baseline NT-proBNP (the standardized coefficient (r)=0.73, p<0.001). The change in NT-proBNP was not associated with changes in eGFR, and was indirectly related with age, BMI, eGFR and loop diuretics (p<0.01 for all). ConclusionsBaseline NT-proBNP was the main determinant of change in NT-proBNP at one year.

NT-proBNP during and after primary PCI for improved scheduling of early hospital discharge.

BackgroundThe Zwolle Risk Score (ZRS) identifies primary percutaneous coronary intervention (PPCI) patients at low mortality risk, eligible for early discharge. Recently, this score was improved by adding baseline NT-proBNP. However, the optimal timepoint for NT-proBNP measurement is unknown.MethodsPPCI patients in the On-Time 2 study were candidates. The ZRS and NT-proBNP levels on admission, at 18–24 h, at 72–96 h, and the change in NT-proBNP from baseline to 18–24 h (delta NT-proBNP) were determined. We investigated whether addition of the different NT-proBNP measurements to the ZRS improves the prediction of 30-day mortality. Based on cut-off values reflecting zero mortality at 30 d, patients who potentially could be discharged early were identified and occurrence of major adverse cardiac events (MACE) and major bleeding until 10 d was registered.Results845 patients were included. On multivariate analyses, NT-proBNP at baseline (HR 2.09, 95% CI 1.59–2.74, p < 0.001), at 18–24 h (HR 6.83, 95% CI 2.94–15.84), and at 72–96 h (HR 3.32, 95% CI 1.22–9.06) independently predicted death at 30 d. Addition of NT-proBNP to the ZRS improved prediction of mortality, particularly at 18–24 h (net reclassification index 29%, p < 0.0001, integrated discrimination improvement 17%, p < 0.0001). Based on ZRS (<2) or NT-proBNP at 18–24 h (<2500 pg/ml) 75% of patients could be targeted for early discharge at 48 h, with expected re-admission rates of 1.2% due to MACE and/or major bleeding.ConclusionsNT-proBNP at different timepoints improves prognostication of the ZRS. Particularly at 18–24 h post PPCI, the largest group of patients that potentially could be discharged early was identified.Electronic supplementary materialThe online version of this article (doi: 10.1007/s12471-016-0935-2) contains supplementary material, which is available to authorized users.

Cardiac and Carotid Markers Link With Accelerated Brain Atrophy: The AGES-Reykjavik Study (Age, Gene/Environment Susceptibility-Reykjavik).

Pathologies in the heart-brain axis might, independently or in combination, accelerate the process of brain parenchymal loss. We aimed to investigate the association of serum N-terminal brain natriuretic peptide (NT-proBNP), as a marker of cardiac dysfunction, and carotid intima media thickness (CIMT), as a marker of carotid atherosclerosis burden, with structural brain changes. In the longitudinal population-based AGES-Reykjavik study (Age, Gene/Environment Susceptibility-Reykjavik), we included 2430 subjects (mean age, 74.6 years; 41.4% men) with baseline data on NT-proBNP and CITM (assessed by ultrasound imaging). Participants underwent a high-resolution brain magnetic resonance imaging at baseline and 5 years later to assess total brain (TBV), gray matter, and white matter volumes. Each unit higher log-transformed NT-proBNP was associated with 3.6 mL (95% confidence interval [CI], -6.0 to -1.1) decline in TBV and 3.5 mL (95% CI, -5.7 to -1.3) decline in gray matter volume. Likewise, each millimeter higher CIMT was associated with 10.8 mL (95% CI, -17.3 to -4.2) decline in TBV and 8.6 mL (95% CI, -14.4 to -2.8) decline in gray matter volume. There was no association between NT-proBNP and CIMT and changes in white matter volume. Compared with participants with low NT-proBNP and CIMT, participants with both high NT-proBNP and CIMT had 3.8 mL (95% CI, -6.0 to -1.6) greater decline in their TBV and 4 mL (95% CI, -6.0 to -2.0) greater decline in GMW. These associations were independent of sociodemographic and cardiovascular factors. Older subjects with both cardiac dysfunction and carotid atherosclerosis are at an increased risk for brain parenchymal loss. Accumulated pathologies in the heart-brain axis might accelerate brain atrophy.

Influence of atrial fibrillation on post-discharge natriuretic peptide trajectory and clinical outcomes among patients hospitalized for heart failure: insights from the ASTRONAUT trial.

Change in NT-proBNP level is a common surrogate endpoint in early phase heart failure (HF) trials, but whether this endpoint is influenced by atrial fibrillation/flutter (AFF) is unclear. This analysis included 1358 patients from the ASTRONAUT trial, which randomized patients hospitalized for HF with EF ≤40% to aliskiren or placebo in addition to standard care. Patients were stratified by presence of AFF on baseline ECG. NT-proBNP was measured longitudinally by a core laboratory at baseline, 1 month, 6 months, and 12 months. Compared with non-AFF patients, AFF patients experienced greater reduction from baseline in log-transformed NT-proBNP (interaction P < 0.001), but this difference was not significant after adjustment (interaction P = 0.726). The ability of aliskiren to lower NT-proBNP during follow-up differed by AFF status (interaction P = 0.001), with aliskiren lowering NT-proBNP more than placebo among non-AFF patients only. After adjustment, baseline AFF was not associated with mortality or HF hospitalization at 12 months (all P ≥ 0.152). In this hospitalized HF cohort, AFF status did not influence post-discharge NT-proBNP trajectory or clinical outcomes after adjustment for patient characteristics. Aliskiren lowered follow-up NT-proBNP levels in patients without AFF, but had no influence among patients with AFF. This study generates the hypothesis that the ability of a HF trial to meet an NT-proBNP defined endpoint may be influenced by the prevalence of AFF in the population. Because aliskiren did not improve outcomes in patients without AFF, this analysis suggests changes in NT-proBNP induced by investigational therapies may be dissociated from clinical effects.

Distribution of circulating cardiac biomarkers in healthy children: from birth through adulthood.

While circulating biomarkers are critical tools for cardiovascular adult care, their relevance in childhood is unknown. We evaluated the behavior of plasma concentrations of clinically relevant cardiac biomarkers (NT-proBNP, hs-cTnI, sST2, Galectin-3) in 106 healthy children. Subjects were divided into age subgroups: 24 newborns (0-30 days), 26 infants (1-12 months), 30 children (1-12 years) and 26 adolescents (13-18 years). Healthy adults were used as control. NT-proBNP (newborns: 504.3 [211.07-942.7] ng/L, median [25-75 percentiles]; infants: 200.64 [76.88-306.73]; children: 97.27 [49.24-271.80]; adolescents: 24.35 [13.14-58.83]; p < 0.001) and hs-cTnI (newborns: 9.3 [3.3-93.8] ng/L; infants: 13.8 [4.82-72.52]; children: 11.45 [4.0-48.10]; adolescents: 2.6[2.07-3.90]; p < 0.001) were highest in the first month of life, showing a decline in the next years. sST2 and Galectin-3 showed no differences. Changes in hs-cTnI and NT-proBNP suggest the design of age- and sex-based reference intervals that will have to be explored in a larger population.

Positive Response to Cardiac Resynchronization Therapy - The Role of NT-proBNP

Abstract Background: Cardiac resynchronization therapy (CRT) is effective, but only 60-70% of patients benefit from the therapy. Despite numerous implantations, identification of predictive factors for response is still a challenge. We sought to assess the correlation of echocardiographic and clinical response to baseline demographics in relation to change in NT-proBNP levels at 6 months. Methods: 211 patients on optimal medical therapy were included retrospectively (72 ± 10 yrs., 66% LBBB, 48% DCMP, 80% male) and investigated at baseline and 6 months later. Improvement of ≥ 1 NYHA class was used as a marker for clinical response, and >15% reduction of left ventricular end-systolic volume was used to de ne reverse remodeling. NT-proBNP levels were measured at baseline and at 6 months and were compared to echocardiographic and clinical response status.Results: Four groups were identi ed: 1) non-responder, 2) echo responder, 3) clinical responder, and 4) double responder (echo and clinical). Responders were younger (70 vs. 74 years, p=0.04), had better NYHA class (2.1 vs. 2.5, p=0.01) and had lower NT- proBNP compared to non-responders at baseline. NT-proBNP slightly increased or remained unchanged in non-responders, whereas reduction in NT-proBNP was of similar magnitude for clinical or echo responders, and was most pronounced for double responders. A reduction of NT-proBNP ≥25% separated non- responders from responders (p=0.01). No signi cant differences in NT-proBNP levels and no signi cant changes in NT-proBNP were found across the responder subgroups.Conclusion: Six-month reduction in NT-proBNP is most pronounced for “double responders, ” but was comparable in patients with either clinical or echo response. Lack of NT-proBNP reduction can help identify the non-responders for further intervention.Keywords Cardiac resynchronization therapy; Electrocardiography; Echocardiography (Less)

Urine measurement indicates the plasma brain natriuretic peptide concentration during optimization of heart failure treatment

Aim: To assess the correlation between the amino-terminal pro-hormone brain natriuretic peptide (NT-proBNP) concentration in blood and urine during a period when actively adjusting the treatment of heart failure (HF). Methods: Plasma and urine analyses of NT-proBNP were compared in 51 patients on admission to and discharge from a nurse-led outpatient clinic where HF treatment was optimized. The median time between the two measurements was 42 days. Correlations were analyzed using linear regression, where R2 is the degree of variability in the plasma NT-proBNP concentration that can be accounted for by the urinary NT-proBNP. Results: There was a statistically significant linear relationship between the urine and plasma concentrations of NT-proBNP on both occasions, but R2 varied greatly depending on how the data were presented. The correlation between the raw data showed an R2 of only 30%, and it almost doubled upon logarithm transformation, which shows that the variability (error) was concentration-dependent. Correction of the urinary NT-proBNP for urinary creatinine further increased R2 for the logarithm-transformed correlation to 68% on admission and 76% on discharge. The highest R2 (77%) was obtained when the relative changes in urinary NT-proBNP/creatinine between admission and discharge were compared with the corresponding relative changes in the plasma concentration. The sensitivity and specificity of the urine in indicating plasma concentration changes > 10% were 82% and 86%, respectively. Conclusion: Relative changes in plasma NT-proBNP could be reliably estimated from urine samples during a period of optimization of HF treatment.

Abstract 19564: Short Term Improvement in Subtle Cardiac Dysfunction in Severely Obese Patients After Bariatric Surgery is Not Associated With Changes in Nt-pro-bnp: A Speckle Tracking Study

Background and objective: The impact of bariatric surgery on sub-clinical alteration of cardiac function assessed using speckle-tracking strain and its relationship with metabolic changes is unknown. We assessed in obese patients with normal left ventricle (LV) systolic function who underwent the biliopancreatic diversion with duodenal switch (BPD-DS); 1) prevalence of subclinical cardiac dysfunction and dyssynchrony in comparison with gender-matched subjects and, 2) the impact of bariatric surgery on myocardial function and its association with changes in NT-proBNP levels and insulin sensitivity. Methods: Prospective, observational study of the effect of BPD-DS after six months on strain, strain rate (SR) and displacement curves using a repeated measures mixed linear regression model analysis. Changes in systolic (LV end-systolic dimension, longitudinal strain) and diastolic (E/A, ESr) parameters were correlated with changes in body mass index (BMI), HOMA and NT-proBNP. Results: Thirty-eight severely obese patients (BMI 48.4±7.4 Kg/m 2 ) had decreased longitudinal strain (-17.0±2.5%) in comparison with 20 patients without obesity (-19.7±1.5%) (p&lt;0.001), which was comparable to controls after surgery (19.3±1.8%) at a mean BMI of 35.7±6 mg/m 2 . Eighteen patients (47%) had a global longitudinal strain considered clinically abnormal. Following surgery, 94% of these patients improved their LV mechanics, with normalization of their global longitudinal strain (p&lt;0.001). Changes in longitudinal strain were not related with changes in NT-proBNP or improvement in insulin sensitivity. Conclusions: There is significant subclinical cardiac dysfunction in patients with severe obesity with normal systolic function. Improvement in longitudinal strain after surgery was not explained by improved insulin sensitivity or changes in NT-proBNP.

Abstract 14223: Atrial Fibrillation, Clinical Outcomes, and Post-discharge Natriuretic Peptide Trajectory Among Patients Hospitalized for Heart Failure: Findings From the ASTRONAUT Trial

Introduction: Heart failure (HF) clinical trials have used change in NT-proBNP as a surrogate endpoint, but the influence of atrial fibrillation/ flutter (AFF) on this endpoint is unclear. We investigated the association of AFF with change in NT-proBNP and clinical outcomes following HF hospitalization. Methods: Characteristics and outcomes of 1,358 patients from the ASTRONAUT trial were compared by presence/ absence of AFF on baseline ECG. Patients with history of AFF but without AFF on ECG were excluded. Full factorial repeated measures design using AFF and study randomization was used to predict NT-proBNP changes from baseline to 1, 6, and 12 months. Survival analysis was used to examine the correlation between AFF and outcomes. Results: Patient characteristics and outcomes are displayed in the Table. Among placebo patients, AFF was associated with higher NT-proBNP level at all time points, but larger reductions from baseline levels (p for interaction &lt;0.01). These differences became non-significant after accounting for other clinical characteristics. The ability of aliskiren to lower NT-proBNP over time differed by AFF status (p for interaction &lt;0.01, Figure). After adjustment for patient characteristics, AFF was not associated with cardiovascular mortality/ HF hospitalization or all-cause death at 12 months (all p≥0.15). Conclusions: Absolute levels and change from baseline in NT-proBNP over time differ in HF patients with and without AFF. The ability of a study drug to lower NT-proBNP may depend on the AFF prevalence in the population. AFF was not independently associated with clinical outcomes in this cohort.

22 The effects of apelin on serum NT-proBNP levels in pulmonary hypertension patients

Background Pulmonary Hypertension has a poor prognosis and therapy is limited to symptomatic relief. Apelin, a new therapy, has the potential to provide both symptomatic relief and address the underlying pathology. Disease severity, in pulmonary hypertension, is measured using NT-proBNP. This study investigated the effects of apelin on serum NT-proBNP levels in groups of pulmonary hypertension patients and controls. Methods Serum samples from patients recruited for a haemodynamic investigation of apelin were used. The groups studied were controls, pulmonary arterial hypertension and pulmonary hypertension due to left heart failure. In the haemodynamic study each patient was given an apelin and placebo infusion separately, over a period of several minutes. Serum samples were taken pre and post infusions. NT-proBNP concentration in the samples was determined using the ABNOVA ELISA kit. Results Across all groups there was no significant change in NT-proBNP levels due to apelin infusion (P = 0.830). There was no significant difference in pre-infusion levels between groups (P = 0.287). Conclusions Apelin infusion, over a period of several minutes, has no effect on NT-proBNP levels in serum. This is consistent amongst control and pulmonary hypertension patients. Despite the lack of change in NT-proBNP seen in this study, the haemodynamic results for apelin were positive. These haemodynamic results have been associated with a decrease in NT-proBNP in other drug studies. The main difference in these studies was a longer time period. As a result, investigation of therapy over a longer time period is required to assess if apelin has any effect on NT-proBNP levels.

Riociguat in Combination With Endothelin Receptor Antagonists (ERAs) for the Treatment of Pulmonary Arterial Hypertension (PAH): A Subgroup Analysis of PATENT

SESSION TITLE: Pulmonary Arterial Hypertension Posters II SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM PURPOSE: The ACCP suggests that riociguat may be added to the treatment regimen of PAH patients who remain symptomatic despite stable regimens of an inhaled prostanoid or an ERA. PATENT-1 (the Pulmonary Arterial Hypertension Soluble Guanylate Cyclase-Stimulator Trial) allowed patients to enroll while on stable regimens of ERAs. Here, we report findings from analysis of the subgroup of patients from the PATENT trial who were on background ERA therapy (BERA). METHODS: Patients were assigned to placebo (N=126; n=54 on BERA), to individualized dosing of riociguat up to 2.5 mg TID (N=254; n=113 on BERA), or to an exploratory riociguat group capped at 1.5 mg TID (N=63; n=27 on BERA). Primary outcome was change from baseline (BL) in 6-minute walk distance (6MWD) at week 12. Secondary exploratory outcomes included change from BL in pulmonary vascular resistance (PVR), NT-proBNP, WHO functional class (WHO-FC), and clinical worsening. RESULTS: All apply to patients (riociguat and placebo) on BERA. For the placebo-corrected mean change from baseline to last visit, 6MWD in riociguat patients (1.0 to 2.5 mg TID) increased by 26 meters (95% CI: 5-46 meters). Mean change in PVR for riociguat patients was -174±202 dyn·s·cm-5, versus -46±266 dyn·s·cm-5 for placebo. Mean change in NT-proBNP was 90±2212 pg/mL for riociguat patients versus 172±759 pg/mL for placebo. By last visit, 26% of riociguat patients had improved one WHO-FC (71% maintained FC, while 4% worsened 1 FC) compared with 13% of placebo patients (76% maintained FC, and 9% and 2% worsened 1 and 2 FC, respectively). Among riociguat patients, only 1 (0.9%) had at least 1 clinical worsening event, compared with 3 (5.6%) among placebo patients, including 1 death. CONCLUSIONS: These data suggest that adding riociguat to stable regimens of ERAs in symptomatic PAH patients has favorable effects on 6MWD, PVR, WHO-FC, and perhaps clinical worsening. CLINICAL IMPLICATIONS: Adding riociguat to stable regimens of ERAs may be beneficial in symptomatic PAH patients but additional studies are needed to further explore this possibility. DISCLOSURE: Nicholas Hill: Consultant fee, speaker bureau, advisory committee, etc.: Bayer Healthcare Namita Sood: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Consultant fee, speaker bureau, advisory committee, etc.: Gilead, Consultant fee, speaker bureau, advisory committee, etc.: Bayer Healthcare No Product/Research Disclosure Information

GW26-e3897 Investigation of detecting plasma lactate and NT-proBNP changes in patients with pulmonary embolism subjected to thrombolytic treatment

GW26-e3897 Investigation of detecting plasma lactate and NT-proBNP changes in patients with pulmonary embolism subjected to thrombolytic treatment