Higher NT-proBNP Concentrations Research Articles

Left atrium volume and function changes during stress in patients with primary mitral regurgitation and preserved left ventricular ejection fraction.

Patients with primary mitral regurgitation (MR) usually remain asymptomatic for a long time due to compensatory mechanisms and an adequate treatment could be delayed. Stress echocardiography and speckle-tracking analysis could help to evaluate impaired left atrium (LA) function before the manifestation of clinically significant myocardial changes in asymptomatic patients with primary MR and preserved left ventricular (LV) ejection fraction (EF). This study prospectively enrolled 91 patients with preserved LV EF (≥60%) at rest, of which 60 patients had moderate-to-severe MR and 31 were healthy controls. Rest and stress (bicycle ergometry) echocardiography and speckle-tracking offline analysis were performed. In MR group LA volume indices were higher at rest and during stress, while LA reservoir, conduit, and contractile fractions were decreased (p < .005). LA deformation parameters at rest were similar in both groups. During maximum stress LA conduit, contractile fractions and reservoir strain were lower (p < .05) in patients with MR. Indices of LA volume were related to SPAP at rest and during stress. Higher NT-proBNP concentrations was associated with higher LA volume indices, decreased contractile and reservoir functions during peak stress (p < .05). LA volume indices, LA EF, and filling index at rest could predict exercise-induced pulmonary hypertension (EIPH) (p < .05). In patients with primary MR and preserved LV EF, LA parameters are related to SPAP and NT-pro-BNP concentration. LA volume indices, LA EF and LA filling index are predictors of EIPH.

Clinical and hemodynamic features of acute pulmonary embolism patients diagnosed in cold weather predicts adverse clinical outcome.

Acute pulmonary embolism (APE) is associated with peak incidence and mortality rate in winter. The present study sought to characterize the clinical and hemodynamic features of cold weather on APE patients. All enrolled 224 APE patients underwent clinical and hemodynamic evaluation and baseline parameters were collected. Recruited patients were grouped by weather pattern on admission into cold and warm weather group. The correlation and prognostic values among cold weather and other variables were analyzed. Compared to warm weather group, patients in cold weather group present with more severe cardiac function, with adverse WHO-functional class (P = 0.032) and higher NT-proBNP concentration [1,853.0 (398.0, 5,237.0) pg/ml vs. 847.5 (56.8, 3,090.5) pg/ml, P = 0.001]. The cold weather group also displayed much critical hemodynamic status and heavier thrombosis load, with higher mPAP (29.1 ± 11.2mmHg vs. 25.6 ± 14.2mmHg, P = 0.045), higher PVR [3.3 (1.7, 6.0) wood units vs. 1.8 (0.9, 3.8) wood units, P < 0.001], higher Miller index (21.4 ± 5.9 vs. 19.1 ± 8.0, P = 0.024), and higher D-dimer levels [2,172.0 (854.5, 3,072.5) mg/L vs. 1,094.5 (210.5, 2,914.5) mg/L, P = 0.008]. Besides, cold weather showed well correlation with the above variables. Survival analysis showed APE patients in cold weather had significantly higher clinical worsening event rate (P = 0.010) and could be an independent predictor of adverse clinical outcome in the multivariate analysis (HR 2.629; 95% CI 1.127, 6.135; P = 0.025). APE patients in cold weather were associated with thrombus overload, cardiac dysfunction, hemodynamic collapse and higher clinical worsening event rate. Cold weather proves to be an independent predictor of adverse clinical outcome.

Influence of NT-proBNP on Efficacy of Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction

BackgroundN-terminal pro–B-type natriuretic peptide (NT-proBNP) is used for diagnostic and prognostic evaluation in heart failure (HF). Previous clinical trials in heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) have shown potential heterogeneity in the treatment response by baseline NT-proBNP levels. ObjectivesThe purpose of this study was to assess the treatment effect of dapagliflozin across baseline levels of NT-proBNP among patients with HFmrEF or HFpEF. MethodsThis was a post hoc analysis from DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure), a randomized, placebo-controlled trial of dapagliflozin in patients with HFmrEF or HFpEF. Elevated NT-proBNP was part of the inclusion criteria (≥300 ng/L for non–atrial fibrillation or flutter [AFF]; ≥600 ng/L for AFF). Baseline NT-proBNP was categorized in quartiles and additionally analyzed continuously. The primary composite outcome was cardiovascular death or worsening HF events. ResultsAmong the 6,262 included patients (mean: 71.7 years and 3,516 [56%] men), the median baseline concentration of NT-proBNP was 716 (Q1-Q3: 469-1,280) ng/L and 1,399 (Q1-Q3: 962-2,212) ng/L for non-AFF and AFF, respectively. Higher NT-proBNP levels were linearly associated with a greater risk of the primary outcome (adjusted HR for log2NTpro-BNP was 1.53 [95% CI: 1.46-1.62] and Q4 vs Q1: 3.46 [95% CI: 2.48-4.22]; P < 0.001), with consistent results regardless of AFF status. The clinical benefit of dapagliflozin was present irrespective of baseline NT-proBNP concentration (P value for interaction = 0.40 by quartiles and = 0.19 continuously for the primary outcome) and the absolute risk reduction was, therefore, greater with higher NT-proBNP concentrations. The effect on health status and safety of dapagliflozin was similarly consistent across NT-proBNP quartiles. ConclusionsDapagliflozin is safe and improves outcomes irrespective of baseline NT-proBNP concentrations in HFmrEF or HFpEF, with the greatest absolute benefit likely seen in patients with higher NT-proBNP concentrations. (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213)

Protein Biomarkers Predict Risk of Gastrointestinal Bleeding in Left Ventricular Assist Device Patients

<h3>Purpose</h3> Recently, protein biomarkers such as N-terminal B-type natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) have been shown to predict risk for gastrointestinal bleeding (GIB) and stroke in atrial fibrillation. This study aims to assess the validity of these biomarkers in predicting the incidence of stroke or GIB in LVAD recipients. <h3>Methods</h3> Prospective LVAD patients were enrolled into the PREVENtion of Heartmate II Pump Thrombosis through Clinical Management (PREVENT) at 24 sites across the U.S along with patients from Inova Heart and Vascular Institute and Allegheny Health Network from 2014-2019. NT-proBNP and GDF-15 were measured before LVAD. Time to first stroke or GIB within 6-months was analyzed in relationship to the median biomarker concentration. <h3>Results</h3> A total of 470 patients were included in the analysis. Patients had the following characteristics: median patient age 60 years (IQR: 52-67), 80% male, 20% female, 75% White, 20% Black, 30% diabetes mellitus and 34% atrial fibrillation. Most patients had non-ischemic cardiomyopathy (46%) and were INTERMACS profile 2-3 (67%). At 6-months, 99 patients had a GIB (21%) and 32 had a stroke (7%). The median NT-proBNP was 2,551pg/ml (1,396-5,386) and GDF-15 was 5,000pg/ml (2,917-8,442). When patients were separated by the median biomarker concentrations, no difference in the incidence of stroke was noted (<i>p</i>=0.8). Similarly, the incidence of GIB with higher NT-proBNP concentrations was not significant (<i>p</i>=0.16, Figure A). Higher GDF-15 concentrations were associated with a higher incidence of GIB (<i>p</i>=0.02, Figure B). Patients with elevated GDF-15 levels had an incidence of GIB of 23% compared to 15% in patients with lower concentrations. <h3>Conclusion</h3> Elevated levels of GDF-15 predict risk of GIB following LVAD implant. These data highlight the ability of novel biomarkers to predict complications that could potentially guide the selection of antithrombotic therapy after LVAD placement.

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

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

Proenkephalin and the risk of new-onset heart failure: data from prevention of renal and vascular end-stage disease.

BackgroundEnkephalins of the opioid system exert several cardiorenal effects. Proenkephalin (PENK), a stable surrogate, is associated with heart failure (HF) development after myocardial infarction and worse cardiorenal function and prognosis in patients with HF. The association between plasma PENK concentrations and new‐onset HF in the general population remains to be established.HypothesisWe hypothesized that plasma PENK concentrations are associated with new‐onset HF in the general population.MethodsWe included 6677 participants from the prevention of renal and vascular end‐stage disease study and investigated determinants of PENK concentrations and their association with new‐onset HF (both reduced [HFrEF] and preserved ejection fraction [HFpEF]).ResultsMedian PENK concentrations were 52.7 (45.1–61.9) pmol/L. Higher PENK concentrations were associated with poorer renal function and higher NT‐proBNP concentrations. The main determinants of higher PENK concentrations were lower estimated glomerular filtration rate (eGFR), lower urinary creatinine excretion, and lower body mass index (all p < .001). After a median 8.3 (7.8–8.8) years follow‐up, 221 participants developed HF; 127 HFrEF and 94 HFpEF. PENK concentrations were higher in subjects who developed HF compared with those who did not, 56.2 (45.2–67.6) versus 52.7 (45.1–61.6) pmol/L, respectively (p = .003). In competing‐risk analyses, higher PENK concentrations were associated with higher risk of new‐onset HF (hazard ratio [HR] = 2.09[1.47–2.97], p < .001), including both HFrEF (HR = 2.31[1.48–3.61], p < .001) and HFpEF (HR = 1.74[1.02–2.96], p = .042). These associations were, however, lost after adjustment for eGFR.ConclusionsIn the general population, higher PENK concentrations were associated with lower eGFR and higher NT‐proBNP concentrations. Higher PENK concentrations were not independently associated with new‐onset HFrEF and HFpEF and mainly confounded by eGFR.

Molecular biomarker profile of heart failure with mid-range and preserved ejection fraction in patients with type 2 diabetes

Aim. To study molecular biomarkers in patients with type 2 diabetes (T2D) in combination with heart failure with preserved (HFpEF) and mid-range ejection fraction (HFmrEF) and compare the data obtained with clinical characteristics of myocardial remodeling.Material and methods. The study included 42 patients with T2D (men — 53%, mean age — 60 years) with clinical manifestations of class II HF: 29 patients with HFpEF (group 1) and 13 patients with HFmrEF (group 2). The control group consisted of 13 healthy people, which were comparable in sex and age and had a normal body mass index (BMI). Patients received stable glucose-lowering and optimal drug therapy for HF for 3 months prior to enrollment in the study. Patients with HFpEF and HFmrEF were comparable in clinical and demographic parameters, had glycated hemoglobin (HbA ) of 8,5% and 8,8%, respectively (p&gt;0,05), increased BMI or grade I-II obesity.We studied following biomarkers: NT-proBNP, highly sensitive C-reactive protein (hsCRP), sST2, galectin-3, procollagen type I C-terminal propeptide (PICP), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1).Results. Volumetric parameters of the left ventricle (LV),LV mass indexed to growth and NT-proBNP were higher in the group of HFpEF patients (p&lt;0,05 for all). The concentrations of galectin-3, PICP were higher, and the MMP-9/TIMP-1 ratio decreased in patients with T2D compared with the control group (p&lt;0,05 for all). PICP values were higher in patients with HFmrEF compared with patients with HFpEF (106,4 (85,4; 140,4) ng/ml vs 46,8 (12,6; 98,6 ng/ml), respectively, p=0,043). In patients with T2D and HF, a relationship was found between TIMP-1 andLV end-diastolic volume (r=-0,68; p=0,042).Conclusion. Patients with HFmrEF and T2D have higherLV volume and mass, higher concentrations of NT-proBNP and PICP in comparison with patients with HFpEF. The direction of MMP-9/TIMP-1 changes may reflect a decrease in antifibrotic processes. Further prospective studies on large samples using a multiple biomarker model are required in T2D and various HF phenotypes.

Type 2 Diabetes Mellitus and Chronic Heart Failure with Midrange and Preserved Ejection Fraction: A Focus on Serum Biomarkers of Fibrosis.

As myocardial fibrosis might be an important contributor to the association of diabetes mellitus with left ventricular (LV) dysfunction and chronic heart failure (HF), we investigated the profile of some proinflammatory, profibrotic biomarkers in patients with type 2 diabetes mellitus (T2DM) at various stages of the cardiovascular disease continuum from absence of clinic since and symptoms to HF with preserved (HFpEF) and midrange ejection fraction (HFmrEF). Material and Methods. Sixty-two patients with T2DM (age 60 [55; 61]), 20 patients without clinical manifestations of HF and 2 groups with clinical manifestations of stable HF, 29 patients with HFpEF, and 13 patients with HFmrEF, were included in the study. The control group consisted of 13 healthy subjects and normal BMI. All patients underwent transthoracic echocardiography, laboratory assessment of N-terminal fragment of the brain natriuretic peptide (Nt-proBNP), highly sensitive C-reactive protein (hsCRP), soluble suppression of tumorigenesis-2 (sST2), galectin-3, C-terminal propeptide of procollagen type I (PICP), N-terminal propeptide of procollagen type III (PIIINP), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix proteinase-1 (TIMP-1). Results. Patients with HFmrEF had higher values of LV volumetric parameters, indexed parameters of LV myocardial mass (LVMM), and higher concentrations of Nt-proBNP (all p < 0.05). The concentrations of galectin-3 were greater in patients with HFpEF and HFmrEF compared to patients without HF (p = 0.01 and p = 0.03, respectively). PICP and PICP/PIIINP ratio were greater in patients with HFmrEF compared to patients with HFpEF (p = 0.043 and p = 0.033, respectively). In patients with T2DM and HF, a relationship was found between galectin-3 and LVMM/body surface area (r = −0.58, p = 0.001), PIIINP, TIMP-1, and LV end-diastolic volume (r = −0.68 and p = 0.042 and r = 0.38 and p = 0.02, respectively). Conclusion. The dynamics at various stages of the cardiovascular disease continuum in the serum fibrosis markers may reflect an increase in fibrotic and decrease in antifibrotic processes already at the preclinical stage of HF. At the same time, the changes found in the circulating procollagen levels may indicate a shift in balance towards type I collagen synthesis in HFmrEF compared with HFpEF.

A chemiluminescence immunoassay for the detection of NT-proBNP

BackgroundThe aim of the study was to assess the analytical performance of the HISCL NT-proBNP assay, a newly developed chemiluminescence immunoassay, for the detection of NT-proBNP. MethodsThe within-run and total imprecision of the NT-proBNP assay were determined with HISCL cardiac marker controls. The linear ranges of the NT-proBNP assays were evaluated based on the CLSI EP6-A document using selected serum samples. Two hundred serum samples were evaluated to compare the HISCL NT-proBNP and Elecsys NT-proBNP assays. Five additional high NT-proBNP concentrations serum samples were evaluated to assess if there was high-dose hook effect in the HISCL NT-proBNP assay. ResultsThe total and within-run imprecision values of the HISCL NT-proBNP assay were 5.85%, 0.81%, 2.56% and 0.54% and 6.07%, 0.73%, 2.61% and 0.59% at 6.1, 129.83, 3732.84and39737.33 pg/ml, respectively. The assay was verified to be linear for NT-proBNP levels ranging between 6.1 and 39737.33 pg/ml. The assay comparison showed that HISCL NT-proBNP = 0.9803 × Elecsys NT-proBNP −4.383. The sensitivity of HISCL NT-proBNP was 87.23%, and the specificity was 85.61%. The AUC of HISCL NT-proBNP (0.90 (95% CI, 0.86–0.93)) did not differ from that of Elecsys NT-proBNP(0.89 (95% CI, 0.85–0.93)) (P = 0.638). The results of five high NT-proBNP concentrations samples (44448, 54206, 55634, 55728 and 109406 pg/ml, measured with the Elecsys NT-proBNP assay) tested with HISCL NT-proBNP assay were all displayed with “>40000 pg/ml”. ConclusionsThe HISCL NT-proBNP chemiluminescence immunoassay showed good analytical and diagnostic performance for the detection of NT-proBNP and could be used in routine clinical practice.

Echocardiographic Assessment of Right Ventriculo-arterial Coupling: Clinical Correlates and Prognostic Impact in Heart Failure Patients Undergoing Cardiac Resynchronization Therapy.

BACKGROUNDRight ventriculo-arterial coupling (RV-PA) can be estimated by echocardiography using the ratio between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP) and it has prognostic value in the general heart failure (HF) population. We aimed to study the clinical correlates and prognostic value of RV-PA in HF patients undergoing cardiac resynchronization therapy (CRT).METHODSWe retrospectively studied 70 HF patients undergoing CRT implantation.RESULTSRV-PA coupling was estimated by TAPSE/PASP ratio using baseline echocardiography. Non-response to CRT was defined as improvement of left ventricular ejection fraction < 5% in a follow-up echo 6-12 months after CRT. Those with lower TAPSE/PASP ratios (worse RV-PA coupling) had higher NT-proBNP concentrations and increased E/e′ ratio. TAPSE/PASP ratio and PASP, but not TAPSE, predicted nonresponse to CRT with TAPSE/PASP ratio showing the best discriminative ability with a sensitivity of 76% and specificity of 71%. Among these parameters, PASP independently predicted all-cause mortality.CONCLUSIONSRV-PA coupling estimated by TAPSE/PASP ratio was associated with established prognostic markers in HF. It numerically outperformed PASP and TAPSE in predicting the response to CRT. Our data suggest that this simple and widely available echocardiographic parameter conveys significant pathophysiological and prognostic meaning in HF patients undergoing CRT.

Amino-terminal Pro-B-Type Natriuretic Peptide Among Patients Living With Both Human Immunodeficiency Virus and Heart Failure.

Among persons living with human immunodeficiency virus (PHIV), incident heart failure (HF) rates are increased and outcomes are worse; however, the role of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations among PHIV with HF has not been characterized. Patients were derived from a registry of those hospitalized with HF at an academic center in a calender year. We compared the NT-proBNP concentrations and the changes in NT-proBNP levels between PHIV with HF and uninfected controls with HF. Among 2578 patients with HF, there were 434 PHIV; 90% were prescribed antiretroviral therapy and 62% were virally suppressed. As compared to controls, PHIV had higher admission (3822 [IQR, 2413-7784] pg/ml vs 5546 [IQR, 3257-8792] pg/ml, respectively; P < .001), higher discharge (1922 [IQR, 1045-4652] pg/ml vs 3372 [IQR, 1553-5452] pg/ml, respectively; P < .001), and lower admission-to-discharge changes in NT-proBNP levels (32 vs 48%, respectively; P = .007). Similar findings were noted after stratifying based on left ventricular ejection fraction (LVEF). In a multivariate analysis, cocaine use, a lower LVEF, a higher NYHA class, a higher viral load (VL), and a lower CD4 count were associated with higher NT-proBNP concentrations. In follow-up, among PHIV, a higher admission NT-proBNP concentration was associated with increased cardiovascular mortality (first tertile, 11.5; second tertile, 20; third tertile, 44%; P < .001). Among PHIV, each doubling of NT-proBNP was associated with a 19% increased risk of death. However, among patients living without HIV, each doubling was associated with a 27% increased risk; this difference was attenuated among PHIV with lower VLs and higher CD4 counts. PHIV with HF had higher admission and discharge NT-proBNP levels, and less change in NT-proBNP concentrations. Among PHIV, VLs and CD4 counts were associated with NT-proBNP concentrations; in follow-up, higher NT-proBNP levels among PHIV were associated with cardiovascular mortality.

Clinical Features and the NT-proBNP Marker in Patients with Chronic Heart Failure in the Setting of Atrial Fibrillation and Chronic Obstructive Pulmonary Disease

Aim: To determine the clinical features and analyse the concentration of the heart failure (HF) marker in patients with atrial fi brillation (AF) and chronic obstructive pulmonary disease (COPD).Materials and methods: 120 patients were divided into the following groups: 1) experimental group including patients with chronic heart failure (CHF), AF and COPD (n = 29); 2) comparison group 1 including patients with COPD, but without cardiovascular diseases (CVD) (n = 28); 3) comparison group 2 consisting of patients with CHF and COPD, but without AF (n = 30); 4) comparison group 3 comprising patients with CHF and AF, but without COPD (n = 33). Clinical symptoms and tolerance to physical load were assessed for all patients with CHF using the clinical condition scale (CCS) and the 6 Minute Walk Test (6MWT), respectively. The severity of dyspnoea was assessed (mMRC scale) in the groups of patients with COPD. The concentration of NT-proBNP was analysed using a Biomedica NT-proBNP reagent pack (SK-1204).Results: A comparative analysis of the CHF clinical manifestations (according to CCS) in the study groups showed higher median values in the group of patients with CHF, AF and COPD, as compared to the same indicator in patients with CHF and AF, but without COPD (p &lt; 0.001). An intergroup analysis of the dyspnoea symptom using the mMRC scale showed the lowest degree of dyspnoea in the group with COPD and without CVD, which signifi cantly differed from the same indicator in patients with CHF and COPD, but without AF (p = 0.015). The 6MWT results did not reveal signifi cant differences between the groups (p = 0.017). In assessing the level of the HF marker, higher concentrations of NT-proBNP were found in the group of patients with CHF, AF and COPD, which exceeded its concentration in patients with CHF and COPD, but without AF (p = 0.0003), as well as in patients with CHF and AF, but without COPD (p = 0.01).Conclusion: 1. Due to the presence of chronic bronchial obstructive syndrome, higher severity of clinical HF symptoms was established in patients with CHF, AF and COPD – as compared to the group including patients with CHF and AF, but without COPD. 2. A statistically signifi cant higher level of NT-proBNP was determined in patients with CHF, AF and COPD, which is associated with the presence of hemodynamic load on both ventricles of the heart under the mutual infl uence of AF and chronic bronchial obstruction on the hemodynamics of the pulmonary circulation.

Role of BNP vs NT-proBNP Testing in the Age of New Drug Therapies: Sacubitril-Valsartan

Sacubitril-valsartan (Entresto), a new dual drug therapy that includes an angiotensin receptor neprilysin (NEP)15 inhibitor (sacubitril), is directed at reducing the risk of cardiovascular death and hospitalization for heart failure (HF) in patients with chronic HF (New York Heart Association classes II–IV) and reduced ejection fraction (HFrEF). Since its approval for the treatment of HFrEF, a commonly raised question has been whether treatment with this drug can complicate the interpretation of B-type natriuretic peptide (BNP) testing results compared to those of the N-terminal proBNP assay because Entresto may interfere with BNP clearance. The clinical and analytical studies addressing this issue are limited. Furthermore, the diversity of both BNP and NT-proBNP assays used in clinical laboratory practice have not been adequately evaluated in clinical trials, and studies to provide an evidence-based conclusion regarding the appropriate assays to use when a patient is on Entresto are lacking. In this article, 5 experts from the US and Europe provide their views regarding this issue. Do you think the differences between BNP and NT-proBNP measurements in patients receiving Entresto are only an early phenomenon because they both seem to be reduced over time? James Januzzi: In the PARADIGM-HF trial, NT-proBNP fell acutely after initiation of Entresto and then continued to drop over time until the end of the trial. Both the enalapril and Entresto arms had a slow, gradual drop in NT-proBNP by the end of trial. This drop likely reflects one of 2 possibilities. First, it may be the subtraction of noncompleters by the end of trial led to a perceived further drop in NT-proBNP (sicker patients that withdrew or died who likely had higher NT-proBNP concentrations). Alternatively, longer treatment with either therapy (angiotensin-converting enzyme inhibitor or angiotensin receptor neprilysin inhibitors) led to further stability, resulting in less synthesis and release of …

Relationship of Natriuretic Peptides with Left Atrial Structure and Function within 1 Month after Electrical Cardioversion in Patients with Persistent Atrial Fibrillation.

Atrial fibrillation (AF) despite the absence of heart failure is related to increased levels of natriuretic peptides (NPs). NPs have not been widely investigated in relation to left atrium (LA) function after sinus rhythm (SR) restoration and duration of AF. The aim of the study was to determine the changes of NPs levels and to define their relation with LA phasic function after electrical cardioversion (ECV). Methods. The study included 48 persistent AF patients with restored SR after ECV. NT-proANP and NT-proBNP were measured for all patients before the ECV. LA phasic function (reservoir, conduit, and pump phases) was assessed using echocardiographic volumetric analysis within the first 24 hours after ECV. Patients were repeatedly tested after 1 month in case of SR maintenance. Results. After 1 month, SR was maintained in 26 (54%) patients. For those patients, NT-proBNP decreased significantly (p=0.0001), whereas NT-proANP tended to decrease (p=0.13). Following 1 month after SR restoration, LA indexed volume decreased (p=0.0001) and all phases of LA function improved (p=<0.01). Patients with AF duration < 3 months had lower NT-proANP compared to patients with AF duration from 6 to 12 months (p = 0.005). Higher NT-proANP concentration before ECV was associated with lower LA reservoir function during the first day after SR restoration (R=-0.456, p=0.005), whereas higher NT-proBNP concentration after 1 month in SR was significantly related to lower LA reservoir function (R=-0.429, p=0.047). Conclusions. LA indexed volume, all phases of LA function, and NT-proBNP levels improved significantly following 1 month of SR restoration. Preliminary results suggest that higher baseline NT-proANP levels and higher NT-proBNP for patients with maintained SR for 1 month are related to lower LA reservoir function. The longer duration of persistent AF is associated with higher NT-proANP concentration.

Abstract 16819: Circulating Growth Factors and Cardiac Remodeling in the Community: The Framingham Heart Study

Cardiac and vascular growth factors may influence myocardial and vascular remodeling through their pro- and anti-angiogenic effects. We hypothesized that higher circulating concentrations of growth factors will be associated with cardiac remodeling patterns consistent with their known biological effects. We related circulating concentrations of vascular endothelial growth factor (VEGF), VEGF-1, angiopoietin 2 (Ang2), Hepatocyte GF (HGF), insulin-like GF (IGF)-1, IGF binding protein (IGFBP)-3, growth differentiation factor-15 (GDF-15), to echocardiographic (echo) indices of cardiac remodeling in 3151 Framingham Study participants (mean age 40 years, 55% women). We evaluated the following echo measures (dependent variables): left ventricular (LV) mass index (LVMi), LV ejection fraction (LVEF), global longitudinal strain (GLS), left atrial ejection fraction (LAEF), and aortic root diameter (AoR) using generalized linear models to account for relatedness. We also related circulating NTProBNP and Troponin (TnI) to echo measures (as positive controls). In multivariable-adjusted analyses blood GDF-15 levels were associated with higher values of LVMi. TnI concentrations were negatively associated with LVEF. IGF-1 and Ang2 concentrations were positively and negatively associated with GLS, respectively. Lower IGFBP-3 concentrations and higher NT-ProBNP concentrations were associated with lower LAEF. Higher VEGF-1, Ang2 and NT-Pro-BNP levels were associated with smaller AoR (Figure). In our large community-based cross-sectional study, we observed patterns of associations between several circulating vascular growth factors and cardiac remodeling indices that are consistent with the known biological effects of these pro- and anti-angiogenic factors on the myocardium and conduit arteries. Additional findings are warranted to replicate our findings and assess their prognostic significance

The effect of BMI, serum leptin, and adiponectin levels on prognosis in patients with non-ischaemic dilated cardiomyopathy.

The recent studies demonstrated that obese heart failure patients have better prognosis - "obesity paradox". The aim of the study was to evaluate the relationship between body mass index (BMI), leptin and adiponectin concentrations and prognosis in patients with heart failure due to non ischeamic dilated cardiomyopathy (NIDCM). 128 patients with NIDCM were included and followed-up for three years. Leptin and adiponectin were measured at baseline using commercially available ELISA tests. Clinical data, routine laboratory parameters, NT-proBNP were assessed as risk factors for reaching the study endpoints: urgent heart transplantation (B), death (C), or combined endpoint death or urgent heart transplantation (D). Patient with adverse outcome had lower BMI and higher NT-proBNP concentration. Leptin was significantly elevated in group C and adiponectin was higher in groups B and D than in survived patients. Patients with leptin concentration below median or with adiponectin concentration above median were more often transplanted in three years follow-up (p = 0.029, p = 0.022, respectively). The cumulative probability of death was greater in patients with concentration of leptin above median (p = 0.024). In the multivariable Cox proportional hazards analyses, increasing leptin and lower BMI were predictors of death. Adiponectin was associated with higher risk of heart transplantation. Both an inverse association of BMI and positive association of leptin and adiponectin with combined endpoint were discovered. Further adjustment to established risk factors abolished association between combined endpoint and BMI, and modestly attenuate with adiponectin and leptin concentration. Evaluation of adiponectin and leptin concentrations was more useful than BMI in prediction of unfavourable outcome in patients with NIDCM. (Endokrynol Pol 2017; 68 (1): 26-34).

Abstract 11912: Glycocalyx Shedding is Markedly Increased During Acute Phase of Takotsubo Cardiomyopathy

Introduction: Acute myocardial infarction (AMI) and other forms of myocardial acute oxidative stress are associated with variable “shedding” of vascular and other glycocalyx. This glycocalyx shedding (GCS) can be quantitated by release into plasma of glycocalyx components such as Syndecan-1 (SD1), which is the most prevalent proteoglycan. Previous in vitro studies have implicated both catecholamines and BNP release as potential accentuating factors in GCS: since these are prominent aspects of the pathogenesis of Takotsubo cardiomyopathy (TTC), we hypothesised that TTC (i) would be associated with increased GCS both acutely and during subsequent 3 months of continued myocardial inflammation and (ii) extent of GCS would be predictable on the basis of NT-proBNP and catecholamine releases. Methods: SD1 concentrations were measured in 49 TTC patients acutely and after 3 months in comparison with 12 normal age-matched controls and 10 myocardial infarct patients. Correlations between SD1 and (i) acute LV function, (ii) lowest BP on admission, (iii) peak catecholamine release, and (iv) extent of systemic and myocardial inflammatory activation [measured by high sensitive C-reactive protein (hsCRP), NT-proBNP concentrations, and myocardial T2 signal intensity on cardiac MRI] were sought. Results: Acute SD1 concentrations in TTC patients were significantly elevated compared to 3 month and control values (2-way ANOVA) (Figure). However, there was no significant difference between acute TTC and MI levels. In addition, there were no correlations between SD1 concentrations and extent of severity of acute episode. Conclusions: 1. TTC, despite minimal associated myocardial necrosis, is associated with marked increase in GCS. 2. Extent of GCS in TTC is not closely related to either release of NT-proBNP or normetanephrine. We postulate that GCS may contribute to some of the clinical features of TTC, such as development of pulmonary oedema without marked increases in PCWP.

New tools to diagnose and follow FAC patients: biomarkers

In the last decade, the availability of the cardiac biomarkers N terminal pro-natriuretic peptide type-B (NT-proBNP) and troponins has radically changed the approach to diagnosis, staging, and response assessment of cardiac amyloidosis. Despite similar appearance at standard imaging, the main types of amyloidosis involving the heart are characterized by different rates of progression and different outcomes. In general, patients with ATTRm amyloidosis have lower concentrations of cardiac biomarkers and usually a better prognosis than subjects suffering from AL amyloidosis. Nevertheless, the clinical manifestations of ATTRm amyloidosis are heterogeneous. Different amyloidogenic TTR mutations give rise to different cardiac phenotypes, ranging from exclusively neuropathic diseases, through mixed phenotypes, to mutation characterized by severe cardiac dysfunction. For instance, one of the mutations associated with cardiac involvement in ATTRm amyloidosis, Ile68Leu, presents with high NT-proBNP concentrations, comparable to those observed in patients with cardiac AL amyloidosis. In our series, survival of patients with Ile68Leu ATTRm is not different from that of cardiac AL patients. Thus, it is possible that NT-proBNP represents a viable marker for early diagnosis of cardiac involvement in ATTR patients with “aggressive” mutations. This marker could be considered in the screening of carriers of these mutations. Despite the lack of systematic studies of cardiac biomarkers in ATTR amyloidosis, the results of several small published series and the analysis of the Pavia patient population, indicate that NT-proBNP and cardiac troponins have prognostic value in this disease, correlating to amyloid burden and adding to known prognostic factors. The availability of several novel therapeutic options for ATTRm, require objective means for the assessment of treatment efficacy in routine clinical practice and in clinical trials. Early results from the Pavia series indicate that NT-proBNP progression portends a poor prognosis, and cardiac biomarkers will probably find their place in the evaluation of response to therapy in ATTRm amyloidosis. Cardiac biomarkers will most likely become increasingly useful in the management of patients with ATTRm amyloidosis in the near future. However, studies of biomarkers in this disease are hindered by small numbers and disease heterogeneity. Prospective studies and international collaboration are warranted to define the role of cardiac biomarkers in the diagnosis and follow-up of cardiac ATTRm amyloidosis.

Cautious application of pleural N-terminal pro-B-type natriuretic peptide in diagnosis of congestive heart failure pleural effusions among critically ill patients.

Background and ObjectiveSeveral studies on diagnostic accuracy of pleural N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) for effusions from congestive heart failure (CHF) conclude that pleural NT-pro-BNP is a useful biomarker with high diagnostic accuracy for distinguishing CHF effusions. However, its applicability in critical care settings remains uncertain and requires further investigations.MethodsNT-proBNP was measured in pleural fluid samples of a prospective cohort of intensive care unit patients with pleural effusions. Receiver operating characteristic curve analysis was performed to determine diagnostic accuracy of pleural NT-proBNP for prediction of CHF effusions.ResultsOne hundred forty-seven critically ill patients were evaluated, 38 (26%) with CHF effusions and 109 (74%) with non-CHF effusions of various causes. Pleural NT-proBNP levels were significantly elevated in patients with CHF effusions. Pleural NT-pro-BNP demonstrated the area under the curve of 0.87 for diagnosing effusions due to CHF. With a cutoff of 2200 pg/mL, pleural NT-proBNP displayed high sensitivity (89%) but moderate specificity (73%). Notably, 29 (27%) of 109 patients with non-CHF effusions had pleural NT-proBNP levels >2200 pg/mL and these patients were more likely to experience septic shock (18/29 vs. 10/80, P<0.001) or acute kidney injury (19/29 vs. 9/80, P<0.001).ConclusionsAmong critically ill patients, pleural NT-proBNP measurements remain a useful diagnostic aid in evaluation of pleural effusions. However, patients with non-CHF effusions may exhibit high pleural NT-proBNP concentrations if they suffer from septic shock or acute kidney injury. Accordingly, it is suggested that clinical context should be taken into account when interpreting pleural NT-proBNP values in critical care settings.

GW24-e2960 Influence of atrial fibrillation on NT-proBNP in the diagnosis of acute heart failure in dyspneic patients

ObjectivesN-terminal pro-brain natriuretic peptide (NT-proBNP) is widely used in the diagnosis and prognostic assessment of heart failure. However, the possible influence of atrial fibrillation (AF) on NT-proBNP in the diagnosis...