NT-pro Brain Natriuretic Peptide Research Articles

Abstract 101: Serum Pro Brain Natriuretic Peptide (pro BNP) Levels In Children With Kawasaki Disease

Introduction: Brain natriuretic peptide (BNP) is a useful biomarker for diagnosing heart failure in adults and children. ProBNP, the precursor form of BNP has been shown to predict myocardial involvement in acute Kawasaki disease (KD) especially in cases of incomplete KD. As the phenotype of KD in North India is different from that in Japan and North America, this study was carried out to validate the utility of proBNP in North Indian children with KD. Objectives: To assay the levels of proBNP in North Indian children with KD. Methodology: Serum pro brain natriuretic peptide (pro BNP and NT-proBNP) levels were estimated in 25 children with Kawasaki disease, both during acute phase and later in convalescence. The levels were similarly assayed in an equal number of age and sex matched controls. The proBNP levels were estimated by an enzyme linked immunosorbent assay (ELISA) using the RayBio Human proBNP ELISA kit which detects both pro BNP and NT-pro BNP. Results: Pro BNP levels were significantly elevated in children during acute phase of KD (4259±8015 pg/ml) when compared to febrile controls (407±542pg/ml) or to children in convalescent phase of KD (509±1066 pg/ml). Pro BNP levels were also higher in children with coronary abnormalities in acute phase. Conclusions: In our experience, pro BNP is a useful biomarker for KD especially with regard to myocardial involvement. ProBNP level is markedly elevated during the acute phase in all children with KD. In children with persistent coronary artery abnormalities, the proBNP level remains elevated even during convalescence. Future impact: ProBNP may be useful marker for children with incomplete forms of KD

Abstract 43: Real Time Polymerase Chain Reaction Assays For Detection Of Respiratory Viruses In Kawasaki Disease Patients

Purpose: Respiratory symptoms are frequently observed in children with Kawasaki disease (KD) during the acute phase. The association rate of KD with antecedent respiratory illness has been reported to range from 56 to 83%. Clinical and epidemiologic features of KD support an infectious cause, but the etiology remains unknown. We investigated the association of respiratory viruses in children with KD using multiplex reverse transcriptase-polymerase chain reaction (RT-PCR). Methods: 138 KD patients were enrolled from January 2010 to June 2013. Two study groups (Group 1; n=94, KD without respiratory symptoms, Group 2; n=44, KD with respiratory symptoms) were compared with a control group (Group 3; n=5, febrile patients with respiratory symptoms). Laboratory data were obtained from each patient including complete blood count (CBC), erythrocyte sedimentation rate (ESR), platelet count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum total protein, albumin, C-reactive protein (CRP), NT-pro brain natriuretic peptide (BNP). Echocardiographic measurements were compared between the three groups. RT-PCR was performed using nasopharyngeal secretion to screen for the presence of 14 viruses (corona virus, parainfluenza virus 1, 2 and 3, influenza A and B, respiratory syncytial virus A and B, rhino virus A, B and C, metapneumo virus, adenovirus, and bocavirus) in groups 2 and 3. Results: The rate of KD with respiratory symptoms was 17.5%. The duration of fever was significantly longer and coronary artery diameter was significantly larger in group 2 than in group 1. Coronary artery diameter, CRP, platelet count, ALT, and NT-pro BNP were significantly higher and albumin lower in group 2 compared with group 3. Detection rate of adenovirus was 55.0% in group 2 and 28.6% in group 3. Conclusion: A positive RT-PCR for respiratory viruses may be helpful to elucidate the specific virus in KD patients with respiratory symptoms. NT-proBNP is a very important diagnostic tool in differentiating KD from other febrile viral respiratory infaction.

Uric acid and mild renal impairment in patients with ST-elevation myocardial infarction

Aims. Mild renal impairment (estimated GFR 60–89 ml/min/1.73 m2) is a strong independent risk factor for mortality in ST-elevation myocardial infarction (STEMI), and is submitted to mechanical revascularization. Patients with renal impairment have decreased excretion of uric acid (UA) and they are thus particularly prone to have elevated serum UA concentrations. This study was aimed at assessing the association between increased UA and mortality in STEMI patients with mild renal impairment. Methods. We prospectively assessed, in 578 STEMI patients with mild renal impairment, whether elevated UA levels are associated with increased mortality both in the short term and in the long term. Results. Patients in the highest UA tertile showed a higher incidence of Killip class III–IV (p = 0.003) and lower values of ejection fraction (EF) (p < 0.001). Lower values for estimated glomerular filtration rate (eGFR) at admission, nadir, and discharge were detected in the highest UA tertile, together with the highest values of peak troponin I (Tn I) (p = 0.002), and NT-proBrain Natriuretic Peptide [NT-proBNP] (p < 0.001). No difference was found in mortality rates (both during their stay in the intensive cardiac care unit [ICCU], and at the 1-year post-discharge follow-up) among the UA tertiles. Conclusions. The UA levels seem to serve as markers of the severity of coronary artery disease, since they identify a subset of patients characterized by an advanced age, more hemodynamic derangement, and reduced renal function. However, neither short nor long-term mortality was affected.

Noninvasive Surrogates for Left Ventricular Filling Pressure in Patients with Valvular Heart Disease

Background: Invasive measurement of left ventricular filling pressure is the gold standard for determining diastolic dysfunction and predicting subsequent outcomes. For repetitive assessment of diastolic function during long-term management, noninvasive surrogates are used. Their reliability and reproducibility should be validated separately for different cardiovascular diseases and conditions. The aim of this study was to identify noninvasive surrogates of invasively derived left ventricular filling pressure and to relate these surrogates to outcomes (death or valve replacement) in patients with stable, asymptomatic valvular heart disease and preserved ejection fraction. Materials and Methods: In a first cohort, we investigated 54 patients who had spiroergometry, echocardiography, and left heart catheterization within a range of 100 days. In a second cohort (n = 64), noninvasive measures were related to outcomes after follow-up of 694 ± 576 days. Transmitral doppler E/tissue doppler E’ (E/E’), E/flow propagation velocity (E/Vp), isovolumetric relaxation time/time to E’-time to E (IVRT/TE’-TE), ventilatory efficiency (VE/VCO2slope), O2 consumption at anaerobic threshold and at peak exercise (VO2AT, VO2peak) as well as NT-pro brain natriuretic peptide (NTpro-BNP) were assessed in relation to left ventricular filling pressure and outcome. Results: NT-proBNP, VO2AT, VE/VCO2slope as well as echocardiographic surrogates E/E’ and E/flow propagation velocity were indicators of elevated end diastolic filling pressure. In multivariable analysis, VO2AT was the only independent predictor. NT-proBNP was the only surrogate of left ventricular filling pressure which predicted outcome. Conclusion: In patients with asymptomatic valvular heart disease and preserved systolic function, spiroergometric parameters and NT-proBNP performed best to assess filling pressure. Only NT-proBNP showed prognostic value in this cohort.

The predictive role of circulating microparticles in patients with chronic heart failure

AimThe study aim was to evaluate whether circulating microparticles with apoptotic or non-apoptotic phenotypes are useful for risk assessment of 3-year cumulative fatal and non-fatal cardiovascular events in CHF patients. MethodsThe incidence of fatal and non-fatal cardiovascular events, as well as the frequency of occurrence of death from any cause in a cohort of 388 patients with CHF during 3years of observation was studied prospectively. Circulating levels of NT-pro brain natriuretic peptide (NT-pro-BNP), high-sensitivity C-reactive protein (hs-CRP), and endothelial apoptotic microparticles (EMPs) were measured at baseline. ResultsMedian follow-up was 2.32years (IQR=1.8–3.1). During follow-up, 110 cardiovascular events (including 43 fatal cases) were determined. Additionally, 74 subjects were hospitalized repetitively due to worsening CHF and also 16 subjects were readmitted in the hospital due to other cardiovascular reasons. In the univariate logistic regression analysis, the main factors independently related with cumulative endpoints were creatinine, fasting glucose, HbA1c, total cholesterol, uric acid, various types of EPMs, NT-pro-BNP, hs-CRP, NYHA class, decreased left ventricular ejection fraction (LVEF) less 45%, and type 2 diabetes mellitus. In multivariate model NYHA class, decreased LVEF (less 45%), NT-pro-BNP, hs-CRP, CD144+/CD31+/annexin V+ EMPs, and CD31+/annexin V+ EMPs remained statistically significant for cumulative endpoint. Adding of CD144+/CD31+/annexin V+ EMCs and CD31+/annexin V+ EMCs to the standard ABC model may improve the relative IDI for cumulative endpoint by 11.4% and 10.5% respectively. ConclusionApoptotic phenotype of circulating microparticles may relate 3-year combined clinical outcomes in CHF patients.

The proposed role of plasma NT pro-brain natriuretic peptide in assessing cardiac remodelling in hypertensive African subjects.

SummaryAimAlthough plasma NT-proBNP differentiates hypertension (HT) with or without left ventricular hypertrophy (LVH) from hypertensive heart failure (HHF), most of the published data are based on studies in Western populations. Also, most previous studies did not consider left ventricular (LV) diastolic function and right ventricular (RV) function. We therefore examined the relation between NT-proBNP on LV and RV remodelling in an African hypertensive cohort.MethodsSubjects were subdivided into three groups after echocardiography: hypertensives without LVH (HT) (n = 83); hypertensives with LVH (HT+LVH) (n = 50); and those with hypertensive heart failure (HHF) (n = 77).ResultsSubjects with HHF had significantly higher NT-proBNP levels compared to the HT+LVH group (p < 0.0002). NT-proBNP correlated positively with right atrial area, an indirect measure of RV function.ConclusionsNT-proBNP is proposed as a useful biomarker in differentiating hypertension with or without LVH from hypertensive heart failure in black hypertensive subjects.

Management and outcomes of patients with reduced ejection fraction after acute myocardial infarction in cardiac rehabilitation centers

Background:We aimed to describe the contemporary management of patients with systolic chronic heart failure (CHF) during a cardiac rehabilitation (CR) stay and present outcomes with focus on lipids, blood pressure, exercise capacity, and clinical events.Methods:Comparison of 3199 patients with moderately or severely impaired left ventricular ejection fraction (low EF, 13.3%) and 20,913 patients with slightly reduced or normal LVEF (normal EF, 86.7%) who underwent an inpatient CR period of about 3 weeks in 2009–2010.Results:Patients with low EF compared to those with normal EF were somewhat older (65.1 vs. 63.0 years, p < 0.0001), and more often had risk factors such as diabetes mellitus (39.7% vs. 32.0%, p < 0.0001) or other comorbidities. The overall rate of patients with regular physical activity of at least 90 minutes per week prior to CR was low overall (54.4%), and reduced in patients with low EF compared to those with normal EF (47.7% vs. 55.5%, p < 0.0001). The rate of patients that achieved lower LDL cholesterol (<100 mg/dl), total cholesterol (<200 mg/dl) and triglyceride (<150 mg/dl) values at discharge increased compared to baseline. Mean blood pressure was substantially lower in the low EF group compared to the normal EF group both at baseline (124/75 vs. 130/78 mmHg, p < 0.0001) and at discharge (119/72 vs. 124/74 mmHg, p < 0.0001). Maximum exercise improved substantially in both groups (at baseline 71 vs. 91 Watts, p < 0.0001; at discharge 85 vs. 105 Watts, p < 0.0001). Event rates during CR were low, and only 0.3% in the low EF group died. As limitations to this study, information on brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-pro BNP) and/or cardiac troponin were not documented, and no long-term information was collected beyond the 3-week CR stay.Conclusions:Patients with CHF account for a considerable proportion of patients in CR. Also patients with moderate/severe EF benefited from participation in CR, as their lipid profile and physical fitness improved.

In-hospital peak glycemia in non-diabetic patients with heart failure complicating acute coronary syndrome

Acute heart failure syndromes (AHF) remain a major cause of morbidity andmortality, in part because of the lack of definitive evidence for AHFmanagement and risk stratification parameters [1], and there is a clinical need to identify clinical and/or laboratory tools useful for risk stratification in the AHF population [2]. The relation between glucose values and insulin resistance and mortality, both at short and long term [3–5], is still poorly understood and previous studies were based only on admission glucose level [6–10], while data on in-hospital glucose values are still lacking. The present investigation was aimed at assessing the prognostic role of admission and peak in-hospital glycemia in 273 consecutive patients with AHF complicating acute coronary syndrome (ACS) and without previously known diabetes, admitted to our Intensive Cardiac Care Unit (ICCU) from June 30, 2009 to December 31, 2012. Even if in all cases datawere collected prospectively, the current study is a retrospective analysis of those data. The study population includes 141 patients with ST-elevation myocardial infarction (STEMI) (51.6%) and 132 (48.4%) patients with Non ST Elevation myocardial infarction (NSTEMI). All patients were submitted to coronary angiography. STEMI patients were admitted to our ICCU after mechanical revascularization. Among NSTEMI patients, 24 (18%) patients underwent urgent coronary artery bypass graft, while percutaneous coronary interventionwas performed in 65 NSTEMI patients (49%) and medical therapy was administered to the remaining 43 NSTEMI patients (33%). The presence of comorbidities was determined by taking the patients' history directly [11]. On ICCU admission, in a fasting blood sample, the following parameters were measured: glucose (g/l), insulin (UI/L), troponin I (Tn I, ng/ml), uric acid (mg/dl), glycated hemoglobin (%), NT-pro Brain Natriuretic Peptide (NT-proBNP) (pg/ml), leukocytes count (*10/μl), fibrinogen (mg/dl) and lactate (mmol/l). Creatinine (mg/dl) was also measured in order to calculate glomerular filtration rate (ml/min/1.73 m) [12]. In all patients, glucose levels and Tn I were measured three times a day, and peak glycemia [13,14] and peak Tn I were considered, respectively. Acute insulin resistancewas investigated bymeans of thehomeostaticmodel assessment index (HOMA index), as previously described [15–17]. Intensive insulin therapy was administered in patients with significant hyperglycemia (that is plasma glucose N180 g/l) [18]. The study population was divided according to tertiles of peak glycemia. Outcome was in-ICCU mortality. The study protocol was in accordance with the Declaration of Helsinki and approved by the local Ethics Committee. Informed consent was obtained in all patients before enrolment. Categorical values have been reported as frequency (percentage); continuous variables have been reported as mean± SD or median (interquartile range, IR) as appropriate. Between-group comparisons were made by means of chi-square and ANOVA or Kruskal–Wallis test as needed. Logistic regression analysis, both uniand multivariable, were carried out considering as outcome intra-ICCU mortality. Variables were chosen as those clinically related to in-ICCU death. A receiver operating characteristic (ROC) curve was plotted to identify a cutoff of peak glycemia with respect to in-ICCU death. A p value less than 5% has been taken as statistically significant (IBM-SPSS 20.0 for Windows® statistical software (IBM-SPSS Inc., USA)). Clinical characteristics of the study population are depicted in Table 1. Patients in the third tertile showed the highest percentage of STEMI, thehighest incidenceof COPDand the lowest valuesof admission and discharge LVEF. The highest in-ICCUmortality rate was observed in patients in the third tertile. Patients with the highest values of peak glycemia showed the highest admission glycemia levels and the highest incidence of HOMA-index and HOMA positivity. In the third subgroup, it was observed a progressive increase in leukocytes count, in NT-pro BNP levels and in peak Tn I. Devices and inotropes were more frequently used in patients in the third tertiles (Table 2). A cutoff of 1.91 g/l peak glycemia was identified with C-statistic as significantly related to an in-ICCU higher mortality rate: AUC, 0.81 (95% CI = 0.74 to 0.87), p b 0.001; sensitivity, 75% (95% CI = 69% to 81%); specificity, 76% (95% CI = 59% to 87%); predictive value of positive test,

Predictive Value of Circulating Apoptotic Microparticles in Patients with Ischemic Symptomatic Moderate-To-Severe Chronic Heart Failure

Aim: To evaluate the prognostic value of circulating CD31+/annexin V+ Microparticles (MPs) for cumulative survival in patients with ischemic Chronic Heart Failure (CHF). Methods: A total of 154 patients with ischemic symptomatic moderate-to-severe CHF were enrolled in the study on discharge from the hospital. Observation period was up to 3 years. Blood samples for biomarkers measurements were collected. Flow cytometry analysis for quantifying the number of CD31+/annexin V+ MPs was used. CD31+/ annexin V+ MPs number for cumulative survival cases due to CHF were tested. Additionally, all-cause mortality, and CHF-related death were examined. Results: During a median follow-up of 2.18 years, 21 participants died and 106 subjects were hospitalized repetitively. Medians of circulating levels of CD31+/annexin V+ MPs in patients who survived and subjects who died were 0.286 n/mL (95% confidence interval [CI] = 0.271-0.309 n/mL) and 0.673 n/mL (95% CI = 0.65-0.74 n/ mL) (P 0.850 n/mL). ROC analysis has been shown that cut off point of CD31+/ annexin V+ MPs number for cumulative survival function was 0.514 n/mL. Area under cure was 0.913 (Std. error = 0.025; 95% CI = 0.863-0.962), sensitivity and specificity were 89.6% and 69.7% respectively. It has been found a significantly divergence of Kaplan-Meier survival curves in patients with high quartile (MPs number >0.514 n/mL) of MPs numbers when compared with low quartiles. Using a stepwise model selection method for multivariable prediction model we investigated that CD31+/annexin V+ MPs number alone and combination of CD31+/annexin V+ MPs number with NT-pro-brain natriuretic peptide (NT-pro-BNP) remained statistically significant predictors for all-cause mortality, CHF-related death, and CHF-related re-hospitalisations, whereas combination of CD31+/annexin V+ MPs with both NT-pro-BNP and left ventricular ejection fraction did not. Conclusion: Increased circulating CD31+/annexin V+ MPs associates with increased 3-year CHF-related death, all-cause mortality, and risk for recurrent hospitalization due to CHF.

Hyper-Prolactinemia in Men With Idiopathic Dilated Cardiomyopathy: Does It Have any Prognostic Implications?

Background:Prolactin (PRL) has increasingly been recognized to play a stimulatory role in inflammatory response. Recently, studies have reported an increase in prolactin level among patients with chronic heart failure, however, there is conflicting data about its role as a prognostic factor in these patients.Objectives:We aimed to measure PRL level in male patients with idiopathic dilated cardiomyopathy (IDC) and its relationship with some prognostic factors.Patients and Methods:Serum prolactin level was assessed in 33 men with a diagnosis of IDC, left ventricle ejection fraction (LVEF) less than 35% on standard medical therapy for heart failure and New York Heart Association class II-III. Serum NT-Pro BNP (N terminal pro brain natriuretic peptide), hs-CRP (High sensitive C reactive protein) and six-minute walk test (6MWT) were also measured. Our secondary endpoints were mortality, transplantation and hospitalization due to acute heart failure and all patients were followed for one year.Results:The mean age was 33 ± 7 years (24-45 years) and the mean LVEF was 23% ± 6.5. The mean PRL level was 16 ± 7.7 ng/mL (95% confidence interval: 13.3-18.7 ng/mL), which was significantly higher than normal reference values (4.04-15 ng/mL) (P < 0.0001). There was no correlation between PRL levels and pro BNP, hs-CRP or 6MWT test, however, the serum PRL level was slightly higher among patients who died or were hospitalized or transplanted.Conclusions:Considering our study results, prognostic implication of PRL should be questioned. However, it seems that the significant increase in serum PRL in the study population needs more consideration and may have its own pathophysiologic importance. Further studies are recommended for better addressing the role of PRL in chronic heart failure patients.

Inhibition Of JAK-STAT Pathway As a Therapeutic Option For Myelofibrosis Associated Pulmonary Hypertension

Pulmonary hypertension (PH) is an under-recognized complication of myelofibrosis (MF) occurring in 30% of MF patients and associated with poor survival. Echocardiographic diagnostic findings include; elevated right ventricular systolic pressure (RVSP)>35 mmHg, right atrial (RA) enlargement and increased tricuspid regurgitation velocity (TRV) ≥2.5 m/sec. The pathophysiology of PH in MF has not been elucidated, although in idiopathic PH, the proliferation of pulmonary artery endothelial cells has been linked to activation of STAT3 pathway. Dysregulation of JAK-STAT pathway has been implicated in the pathogenesis of MF. Ruxolitinib, a JAK1/2 inhibitor, was approved for management of splenomegaly and cytokine-mediated symptoms in MF. Furthermore, no specific therapy in the management of MF-associated PH has been established. Given the association between MF and PH and the possible pathophysiologic link mediated by JAK signaling, we prospectively followed 19 patients with MF-associated PH and compared their echocardiographic findings and PH relevant serum biomarker levels (nitric oxide [NO], NT-pro brain natriuretic peptide [NT-proBNP], von Willebrand antigen (vWB), ristocetin co-factor (RCA), and uric acid (UA) pre- and post-ruxolitinib therapy. All categorical data were summarized for frequency, counts and percentages, and the comparison between two groups was performed by two-sample Wilcoxon signed rank test. Among 19 patients (pts), 9 had PMF, 5 post-ET MF, 4 post-PV MF and one CMML-1. In this cohort, 11 were females and 8 were males. The median age of the cohort was 68 years (range, 50-81 years). Fifteen pts were JAK2 V617F positive and 4 were wild-type, 8 were intermediate-1, 4 intermediate-2 and 6 high risk per Dynamic International Prognostic Scoring System-Plus risk grouping. The mean ruxolitinib dose was 10 mg BID (range: 5 mg QOD-20 mg BID]. Median duration of disease was 32 mos (6-164 mos), ruxolitinib duration of treatment was 10 mos (4 -17 mos) and follow-up was 11 mos (6-22 mos). Prior to the initiation of ruxolitinib treatment, NT-pro BNP levels, were measured and found to be elevated in 90% (17/19) of pts. In addition, UA, vWB, and RCA levels were all elevated in 47% (9/19), 24% (4/17), and 12% (2/17) of pts respectively. The strongest correlation among serum biomarkers was between plasma vWB and RCA levels (r2=-0.89, P=<.001). The biomarker most closely associated with elevated NT-pro BNP was UA both in the pre- (r2=-0.53, P=.065) and post-treatment (r2=-0.64, P=.019) settings. Echocardiographic findings by TTE pre- and post ruxolitinib therapy were available for 12 pts (63%). All 12 had documented PH with a mean RVSP of 47.5 mm Hg (42-68) [normal pressure ≤30 mmHg]. Echocardiographic evidence correlated with RCA (r2=-0.64, P= .045) and plasma NT-pro BNP levels (r2=-0.8, P=.013). Ruxolitinib resulted in reductions in NT-pro BNP level (88%) (p=.013), plasma UA levels in (71%), vWB (71%), and RCA (71%) (P=.045). Nitric oxide, a primary regulator of vascular endothelial function is reduced in MF patients with PH compared to normal individuals (median NO, 36 vs 65 pM). Treatment with ruxolitinib resulted in marked increase in NO levels compared to baseline (68 pM vs 36 pM; P=0.04) while no changes in NO levels were observed after treatment with hydroxyurea and lenalidomide (N=10). Treatment with ruxolitinib also resulted in reduction of key cytokines (TNF-α, IL-4, IL-10) that inhibit NO production and induction of cytokines (IFN-γ) that lead to increase in NO synthesis supporting the role of cytokines in PH pathogenesis in MF. Murine studies further supported the role of ruxolitinib in induction of NO levels. Eight normal CD-1 mice were treated with ruxolitinib (50 mg/kg p.o. daily for 5 days for three consecutive cycles with 14 day intervals between each cycle). After the first cycle, NO levels were significantly higher compared to baseline followed by significant increase compared to baseline at cycle 3 (P=.04). In addition, PH mice (Caveoline-1 mice) have been bred and undergoing treatment with ruxolitinib to assess changes in NO levels and its impact in improving of PH. In conclusion, aberrant JAK-STAT signaling in MF mediates PH by dysregulation of NO and cytokines levels which can be restored by therapy with JAK inhibitors. This suggests that inhibition of the JAK-STAT signaling pathway is a novel and viable target for the management of patients with MF-associated PH. Disclosures:No relevant conflicts of interest to declare.

Pulmonary Hypertension in Sickle Cell Disease: Correlation With Echocardiographic Assessment and Serum Brain Natriuretic Peptide Concentration

Background &amp; Purpose Pulmonary hypertension (PH) in sickle cell disease (SCD) is an important risk factor for complications including sudden death. In this study, we aimed to determine the prevalence of PH and correlate the echocardiographic parameters and general laboratory data with markers of hemolysis and serum NT pro-brain natriuretic peptide [BNP] concentrations in Omani SCD patients. Methods A cohort of 163 SCD patients [Mean age 25.4±8.4 years], in steady state was prospectively screened for PH with Doppler echocardiography (defined as a tricuspid regurgitation jet flow velocity of ≥ 2.5 m/sec and/or mean pulmonary artery pressure [mPAP] ≥25 mmHg). After a written informed consent, all patients were investigated with a complete blood count, renal chemistry, hemolytic parameters including LDH, haptoglobin, liver function tests, coagulation studies, HPLC studies including HbS and HbF level estimations, X ray Chest, ECG, ABG, Pulmonary function tests, Pulse oximetry, and Serum NT pro-BNP levels. Results In the evaluable patient cohort of 116 subjects [63 females, 53-males], the prevalence of PH was 5.2%. No statistically significant differences were detected in Hb levels, ECG, chest radiography, pulmonary function tests between patients with and without PH. However, plasma NT pro-BNP levels were significantly correlated with PAH [r=0.934, p&lt;0.000], TRV jet [r=.671, p&lt;0.000], Abnormal ECHO [r=0.672, p&lt;0.000], and direct Bilirubin levels [r=0.278,p&lt;0.009] in SCD patients. Furthermore, in SCD patients with PH, there was a statistically significant increase in plasma NT pro-BNP levels [ p&lt;0.001], ALT [p&lt;0.02], S. Creatinine [p=0.045] and Total bilirubin [p&lt;0.0001] and direct Bilirubin levels [p&lt;0.0001][Table]. Conclusions Serum NT pro-BNP is a strong indicator of PH in SCD patients. Doppler ultrasound echocardiography is a useful initial screen for PH in SCD patients. The correlation between PH and hemolytic markers suggests an implication in the pathogenesis of PH. Disclosures: No relevant conflicts of interest to declare.

N-terminal pro-B-type natriuretic peptide as a predictor of incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis: the effects of age, sex and ethnicity

ObjectiveAtrial fibrillation (AF) is a common source of medical costs, morbidity and mortality. NT pro-brain natriuretic peptide (BNP) is a remarkably strong predictor of AF in older whites; we aimed...

The value of use of amino-terminal brain naturitic peptide as marker in cases of pleural effusion of different etiologies

BackgroundThe criteria of Light et al. have been used to make the differentiation between transudate and exudate effusion for the past 25years. The main problem with those criteria is that although they identify nearly all exudates correctly, they misidentify about 20–25% of transudates as exudates.The plasma NT-proBNP level is a sensitive marker of cardiac dysfunction and has proved to be a useful tool for the identification and management of systolic and diastolic cardiac dysfunction. ObjectiveThe aim of this work was to study the value of pleural NT-pro brain natriuretic peptide in the diagnosis of pleural effusion of different causes in comparison to the conventional diagnostic procedures in cases of pleural effusion. Subjects and methodsThe present study was conducted on 32 patients who suffered from pleural effusion, they were classified according to Light’s criteria into two groups namely transudate, exudate, and the third group of 10 normal healthy subjects as control group. ResultsThe levels of both serum and pleural fluid pro-BNP in group I patients with transudate effusion were significantly higher than group II patients with exudate effusion (P>0.001, 0.003) respectively. ConclusionThe results support the feasibility of using the pleural fluid amino terminal proBNP measurement in thoracentesis that would enhance discrimination among the different causes of pleural effusion especially for heart failure patients. Serum and pleural fluid levels of NT-pro BNP were closely correlated and measurement of NT-pro BNP in serum showed equally good diagnostic properties.

The immune protein MD-2 is a novel independent predictor for long term mortality in dilated cardiomyopathy and non-inferior to nt-pro BNP

Background: Myeloid Differentiation protein 2 (MD-2) is strongly involved in activation of the innate immune receptor Toll-Like Receptor 4 (TLR4). Its role in cardiac diseases is unknown. Since cardiac inflammation is often associated with heart failure, we investigated in the present study the impact of MD-2 level at first hospital admission in patients with Dilated Cardiomyopathy (DCM) on long term mortality. Methods and results: We included 174 patients between 2005 and 2011 with biopsy-proven DCM in our study. MD-2 protein expression in serum from patients was quantified by ELISA (USCN Life Science, USA) and nt-pro brain natriuretic peptide (nt-pro BNP) level were quantified during routine diagnostics at first hospital admission. The primary end point of this study was all-cause mortality. Information on vital status of patients was obtained from official resident data files. For descriptive statistics the study population was divided into two groups according to the patients' MD-2 measurement (≥ and < median of all patients). Survival analysis was done calculating Kaplan–Meier curves and log-rank test was used for curve comparison. Multivariable Cox regression models were applied to assess the association between MD-2 level and all-cause mortality, with adjustment for age and cardiovascular risk factors. A value of p < 0.05 was considered statistically significant. All-cause mortality in DCM patients with MD-2 level ≥ overall median (302.44 ng/ml) was strongly associated with increased mortality when compared to patients with MD-2 level < overall median (31.0% versus 8.1%, p<0.001). Multivariable Cox regression analyses demonstrate, that this effect was independent from age, LV ejection fraction and other cardiovascular risk factors including diabetes, BMI, arterial systolic and diastolic blood pressure and smoking with a hazard ratio of 1.004 (p<0.001) for MD-2 as continuous variable. ROC analyses showed no statistically difference between prediction of mortality regarding MD-2 vs. nt-pro BNP (AUC: 0.79 versus 0.74, p=0.40). Conclusion: MD-2, quantified at first hospital admission, is an independent predictor for mortality in DCM and is non-inferior to nt-pro BNP suggesting a relevant role of this protein in the pathophysiology of DCM.

Brain natriuretic peptide is not predictive of dilated cardiomyopathy in Becker and Duchenne muscular dystrophy patients and carriers

BackgroundCardiomyopathy is reported in Duchenne and Becker muscle dystrophy patients and female carriers. Brain Natriuretic peptide (BNP) is a hormone produced mainly by ventricular cardiomyocytes and its production is up regulated in reaction to increased wall stretching. N-terminal-proBNP (NT-proBNP) has been shown to be a robust laboratory parameter to diagnose and monitor cardiac failure, and it may be helpful to screen for asymptomatic left ventricular dysfunction. Therefore we tested whether NT-proBNP can distinguish patients with Duchenne or Becker muscular dystrophy patients and carriers of a dystrophin mutation with a dilated cardiomyopathy from those without.MethodsIn a cohort of Duchenne and Becker muscle dystrophy patients (n = 143) and carriers (n = 219) NT-proBNP was measured, and echocardiography was performed to diagnose dilated cardiomyopathy (DCM).ResultsIn total sixty-one patients (17%) fulfilled the criteria for DCM, whereas 283 patients (78%) had an elevated NT-pro BNP. The sensitivity of NT-proBNP for DCM in patients or carriers was 85%, the specificity 23%, area under the ROC-curve = 0.56. In the specified subgroups there was also no association.ConclusionMeasurement of NT-pro BNP in patients suffering from Duchenne or Becker muscular dystrophy and carriers does not distinguish between those with and without dilated cardiomyopathy.

Tissue Doppler Imaging and Plasma N-Terminal Probrain Natriuretic Peptide for the Identification of Hypertrophic Cardiomyopathy Mutation Carriers

Previous studies have shown that tissue Doppler imaging (TDI) is able to identify mutation carriers of hypertrophic cardiomyopathy (HC) before the development of the clinical phenotype. However, data are scarce and have sometimes been controversial. We performed a systematic study that included conventional echocardiography, TDI, and plasma NT-probrain natriuretic peptide (NT-proBNP) measurement to evaluate the parameters that could identify HC mutation carriers. A total of 138 genotyped subjects were included and divided into 3 groups: group 1, those with HC (n= 62); group 2, mutation carriers (first-degree relatives with a positive genotype but negative phenotype; n= 34); and group 3, controls (first-degree relatives with a negative genotype and phenotype; n= 42). An echocardiographic study, including TDI, was performed on all subjects, and a TDI-derived index (global function index) was also determined. The age-adjusted mean differences in the echocardiographic and TDI parameters and NT-proBNP levels were compared among the 3 groups. Compared with the HC group, the carriers had significantly higher mean E' velocities, lower mean E/E' ratio, higher mean S' velocities, and lower mean global function index and NT-proBNP values. The carriers and controls did not differ significantly either in the echocardiographic parameters studied or in the NT-proBNP levels. In conclusion, the echocardiographic and TDI parameters and NT-proBNP levels cannot be used to identify the HC mutation carrier state and therefore do not appear to be reliable for the purpose of making a preclinical diagnosis of the disease.

β-Adrenergic Blockade for Anthracycline- and Trastuzumab-Induced Cardiotoxicity

Breast cancer is the second leading cause of cancer-related death among women in the United States.1 Approximately 25% to 30% of breast cancers have overexpression of human epidermal growth factor receptor 2 (HER2), which is associated with an adverse prognosis.2 Adjuvant chemotherapy with trastuzumab, the humanized monoclonal antibody that directly targets HER2, significantly improves disease-free and overall survival in these patients.3 However, trastuzumab, especially when given in combination with anthracyclines, has been associated with asymptomatic and symptomatic left ventricular (LV) dysfunction3 that can lead to premature discontinuation of trastuzumab therapy and significant cardiac morbidity. Article see p 420 In this issue of Circulation: Heart Failure , Seicean et al4 retrospectively evaluated the incidence of new symptomatic heart failure (HF) in patients with breast cancer treated with anthracyclines, trastuzumab, or both, at the Cleveland Clinic between 2005 and 2010. Using 1:2 propensity matching, they compared patients on continuous β-blockers during cancer treatment to those not on β-blockade, and assessed the effect of incidental β-blocker use on new symptomatic HF and noncardiac mortality during a median follow-up of ≈3 years. The results of this study show that trastuzumab, when given alone or in combination with anthracyclines, substantially increased the risk of symptomatic HF compared with anthracyclines alone (hazard ratio, 9.5; 95% confidence interval, 3.9–23.1). Furthermore, incidental β-blocker use significantly reduced the incidence of symptomatic HF (hazard ratio, 0.2; 95% confidence interval, 0.1–0.7) but did not affect noncardiac mortality in patients with breast cancer treated with trastuzumab, anthracyclines, or both. This article highlights 2 important issues: (1) it emphasizes the magnitude of trastuzumab cardiotoxicity in the real world, and (2) it provides support for the hypothesis that prophylactic β-blocker use may be cardioprotective in patients receiving trastuzumab, anthracyclines, or both. Anthracyclines cause a dose-dependent toxicity that is felt …

Clinical application value of NT-proBNP levels in evaluating dry weight of patients in maintenance hemodialysis

Objective To investigate the relationship between plasma NT-pro brain natriuretic peptide (NT-proBNP) levels and dry weight in patients in maintenance hemodialysis (MHD) and to evaluate the clinical value of NT-proBNP in the assessment of dry weight.Methods NT-proBNP level was determined in 18 cases of MHD patients with well-controlled dry weight and 20 eases of MHD patients with bad-controlled dry weight,while the latter would be checked once again after the weight was down-regulated to dry weight in 4 weeks.Results The average level of NT-proBNP was 3419.3(2368.7～5728.3) pg/ml which was higher than normal.Plasma NT-proBNP levels were significantly lower in patients with well-controlled dry weight than those patients with bad-controlled dry weight (2872.4 vs 4568.4) pg/ml,and there was very significant difference in plasma NT-proBNP levels between pre and post treatment of down-regulation to dry weight in patients with bad-controlled dry weight (4568.4 vs 2569.0) pg/ml.Conclusions Plasma NT-proBNP can be a good marker for the evaluation of dry weight in MHD patients. Key words: Hemodialysis; NT-proBNP; Dry weight

Intra-arterial thrombolysis facilitated by ultrasound in submassive pulmonary embolism: first documented case report in Italy

A 76-year-old woman presented with a one-week history of dyspnea on minimal exertion and at rest. In the emergency room she underwent echocardiography and thoracic computed tomography scan with diagnosis of bilateral pulmonary embolism. Due to right ventricular dilatation and increasing values of NT-probrain natriuretic peptide, both markers of high risk that classify pulmonary embolism as "submassive" according to current international guidelines, we opted for thrombolysis. The patient underwent intra-arterial bilateral pulmonary thrombolysis facilitated by ultrasound, the first case in Italy. The patient recovered from pulmonary embolism after 10h of therapy, with improved gas exchange and symptoms. Subsequently, she developed arterial bleeding at the puncture site, due to accidental puncture of a branch of the femoral artery. The patient was treated with percutaneous embolization and transfusions. In patients with pulmonary embolism, even if not massive, thrombolysis should be considered, especially in the presence of high-risk markers. Direct intra-arterial pulmonary thrombolysis, facilitated by ultrasound, is an effective procedure that provides an alternative to conventional thrombolysis with the advantage of a lower thrombolytic dose.