Natriuretic Protein Research Articles

Late Effects of Total-Body Gamma Irradiation on Cardiac Structure and Function in Male Rhesus Macaques.

Heart disease is an increasingly recognized, serious late effect of radiation exposure, most notably among breast cancer and Hodgkin's disease survivors, as well as the Hiroshima and Nagasaki atomic bomb survivors. The purpose of this study was to evaluate the late effects of total-body irradiation (TBI) on cardiac morphology, function and selected circulating biomarkers in a well-established nonhuman primate model. For this study we used male rhesus macaques that were exposed to a single total-body dose of ionizing gamma radiation (6.5-8.4 Gy) 5.6-9.7 years earlier at ages ranging from ∼3-10 years old and a cohort of nonirradiated controls. Transthoracic echocardiography was performed annually for 3 years on 20 irradiated and 11 control animals. Myocardium was examined grossly and histologically, and myocardial fibrosis/collagen was assessed microscopically and by morphometric analysis of Masson's trichrome-stained sections. Serum/plasma from 27 irradiated and 13 control animals was evaluated for circulating biomarkers of cardiac damage [N-terminal pro B-type natriuretic protein (nt-proBNP) and troponin-I], inflammation (CRP, IL-6, MCP-1, sICAM) and microbial translocation [LPS-binding protein (LBP) and sCD14]. A higher prevalence of histological myocardial fibrosis was observed in the hearts obtained from the irradiated animals (9/14) relative to controls (0/3) (P = 0.04, χ(2)). Echocardiographically determined left ventricular end diastolic and systolic diameters were significantly smaller in irradiated animals (repeated measures ANOVA, P < 0.001 and P < 0.008, respectively). Histomorphometric analysis of trichrome-stained sections of heart tissue demonstrated ∼14.9 ± 1.4% (mean ± SEM) of myocardial area staining for collagen in irradiated animals compared to 9.1 ± 0.9 % in control animals. Circulating levels of MCP-1 and LBP were significantly higher in irradiated animals (P < 0.05). A high incidence of diabetes in the irradiated animals was associated with higher plasma triglyceride and lower HDLc but did not appear to be associated with cardiovascular phenotypes. These results demonstrate that single total-body doses of 6.5-8.4 Gy produced long-term effects including a high incidence of myocardial fibrosis, reduced left ventricular diameter and elevated systemic inflammation. Additional prospective studies are required to define the time course and mechanisms underlying radiation-induced heart disease in this model.

The prognostic value of biomarkers in stroke.

BackgroundIschemic injury triggers inflammatory cascades and changes in the protein synthesis, neurotransmitters and neuro-hormones in the brain parenchyma that may further amplify the tissue damage. The “Triage® Stroke Panel”, a biochemical multimarker assay, detects Brain Natriuretic Peptide (BNP), D-Dimers (DD), Matrix-Metalloproteinase-9 (MMP-9), and S100β protein generating a Multimarker index of these values (MMX). The aims of this prospective study in consecutive patients with ischemic or hemorrhagic stroke were to assess: 1) the rate of an increase of biomarkers (BNP, D-dimer, MMP-9 and S-100β) tested with the Triage Stroke Panel; 2) the correlation between the increase of these biomarkers and functional outcome at 4 months; 3) the risk factors for the increase of biomarkers.MethodsThe outcome of the study was 120-day mortality and it was compared in patients with Stroke Panel >4 and ≤4. Multiple logistic regression analyses were performed to identify independent predictors for death and for the increase of biomarkers.Results244 consecutive patients (mean age 73.02 years; 53.7 % males) were included in the study; 210 ischemic strokes and 34 hemorrhagic strokes. 161/244 (66.0 %) had an increase of biomarkers. At 120 days, 85 patients had died (34.8 %). Death was seen in 68/161 patients with an increase of biomarkers (42.2 %) compared with 17/83 patients without (20.5 %). Regression logistic analysis found that a Stroke Panel >4 (OR 3.1; 95 % CI 1.5–6.2, p = 0.002) was associated with mortality. The increase of biomarkers was independently predicted by an increase of PCR on admission (OR 2.9, 95 CI 1.4–6.0, p = 0.003).ConclusionsAn increase of biochemical markers such as BNP, D-Dimers, MMP-9, and S100β tested with a Triage Stroke Panel (>4) was correlated with mortality at 120 days from stroke onset.

Whole Genome DNA Methylation Analysis of Obstructive Sleep Apnea: IL1R2, NPR2, AR, SP140 Methylation and Clinical Phenotype.

We hypothesized that DNA methylation patterns may contribute to disease severity or the development of hypertension and excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA). Illumina's (San Diego, CA, USA) DNA methylation 27-K assay was used to identify differentially methylated loci (DML). DNA methylation levels were validated by pyrosequencing. A discovery cohort of 15 patients with OSA and 6 healthy subjects, and a validation cohort of 72 patients with sleep disordered breathing (SDB). Microarray analysis identified 636 DMLs in patients with OSA versus healthy subjects, and 327 DMLs in patients with OSA and hypertension versus those without hypertension. In the validation cohort, no significant difference in DNA methylation levels of six selected genes was found between the primary snoring subjects and OSA patients (primary outcome). However, a secondary outcome analysis showed that interleukin-1 receptor 2 (IL1R2) promoter methylation (-114 cytosine followed by guanine dinucleotide sequence [CpG] site) was decreased and IL1R2 protein levels were increased in the patients with SDB with an oxygen desaturation index > 30. Androgen receptor (AR) promoter methylation (-531 CpG site) and AR protein levels were both increased in the patients with SDB with an oxygen desaturation index > 30. Natriuretic peptide receptor 2 (NPR2) promoter methylation (-608/-618 CpG sites) were decreased, whereas levels of both NPR2 and serum C type natriuretic peptide protein were increased in the SDB patients with EDS. Speckled protein 140 (SP140) promoter methylation (-194 CpG site) was increased, and SP140 protein levels were decreased in the patients with SDB and EDS. IL1R2 hypomethylation and AR hypermethylation may constitute an important determinant of disease severity, whereas NPR2 hypomethylation and SP140 hypermethylation may provide a biomarker for vulnerability to EDS in OSA. A commentary on this article appears in this issue on page 723.

Computerized tomography measured liver fat is associated with low levels of N-terminal pro-brain natriuretic protein (NT-proBNP). Multi-Ethnic Study of Atherosclerosis

Background and AimsN-terminal pro B-type natriuretic peptide (NT-proBNP) is inversely associated with diabetes mellitus, obesity and metabolic syndrome. We aim to characterize the association between NT-proBNP and nonalcoholic fatty liver disease (NAFLD), a condition strongly associated with metabolic syndrome. Methods4529 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) free of cardiovascular disease, without self-reported liver disease and not diabetic at their baseline visit in 2000–2002 were included in this analysis. NAFLD was defined by a liver attenuation <40 HU. Relative prevalence (RP) for NAFLD was assessed adjusted for age, race, and sex, percentage of dietary calories derived from fat, total intentional exercise, alcoholic drinks per week, and interleukin-6 by quintiles of NT-proBNP. Adjusted linear spline model was used to characterize a non-linear association between NT-proBNP and liver fat. The inflection point (IP) was the NT-proBNP concentration where there was a change in slope in the association between liver attenuation and NT-proBNP. ResultsRP for NAFLD decreased by 30% from the lowest to the highest quintile of NT-proBNP, p=0.01. We observed an inverse linear association between NT-proBNP and liver fat, which plateaued (IP) at an NT-proBNP concentration of 45pg/mL. Linear regression coefficient (SE) per unit of NT-proBNP less than and greater than or equal to IP was of 0.05 (0.02), p=0.001 and 0.0006 (0.0008), p=0.5, respectively; differences between slopes, p<0.0001. ConclusionsIn this cross-sectional study of a community based multiethnic sample of non-diabetic adults, low levels of NT-proBNP are associated with greater prevalence of NAFLD.

Abstract WMP78: Follow-up High-Sensitivity C-reactive Protein is Associated With Early Recurrent Ischemic lesions in Acute Ischemic Stroke

Background: Early recurrent ischemic lesions (ERILs) on diffusion-weighted imaging (DWI) after acute ischemic stroke have been considered as a potential marker of early recurrent symptomatic stroke. The aim of this study to explore the impact of High-sensitivity C-reactive protein (hsCRP) levels at different time points on ERILs. Method: We prospectively enrolled 484 patients with acute ischemic stroke who underwent DWI and whose plasma and serum biomarkers (hsCRP, D-dimer, and brain natriuretic protein [BNP]) within 24 hours of onset and subsequently at 7 days after onset. Baseline characteristics, stroke features, initial National Institutes of Health Stroke Scale (NIHSS) score, and DWI lesion volume were recorded. ERILs were defined as new ischemic lesions on 7-day DWI, which were outside the vascular territory of index stroke with arterial occlusion and the same or outside the vascular territory of index stroke with arterial stenosis. Results: ERILs were observed in 146 patients (30.2%). In univariate analysis, atrial fibrillation (p=0.040), higher initial NIHSS score (p&lt;0.001), larger DWI infarct volume (p&lt;0.001), stroke subtype (p&lt;0.001), elevated initial and follow-up BNP (p=0.014 and p=0.003) and D-dimer (p=0.009 and p=0.011), and elevated follow-up hsCRP (p&lt;0.001) were positively associated and combination of anticoagulation and antiplatelet therapy after admission (p=0.002) was negatively associated with ERILs. In multivariate analysis, combination of anticoagulation and antiplatelet therapy after admission (Odds ratio [OR], 0.462; 95% confident interval [CI], 0.272 to 0.785; p=0.004) and follow-up log hsCRP (OR, 1.389; 95% CI, 1.054 to 1.830; p=0.020) were independent predictors of ERILs. Conclusions: Underlying inflammation after acute ischemic stroke may be associated with ERILs.

Predictive factors of resistance to intravenous immunoglobulin and coronary artery lesions in Kawasaki disease.

PurposeWe conducted a study to determine which factors may be useful as predictive markers in identifying Kawasaki disease (KD) patients with a high risk of resistance to intravenous immunoglobulin (IVIG) and developing coronary artery lesions (CAL).MethodsWe enrolled 287 patients in acute phase of KD at a single center. The demographic, clinical and laboratory data were collected retrospectively.ResultsThere were 34 patients in the IVIG resistant group. The IVIG resistant group had significantly higher serum N-terminal-pro-brain natriuretic protein (NT-proBNP) levels (P<0.01) and polymorphonuclear neutrophil (PMN) percentage (P<0.01) in comparison to the IVIG responders. The results yielded sensitivity (78.8%, 60.6%), specificity (58.2%, 90%) and cutoff value (628.6 pg/mL, 80.3%) of NT-proBNP and PMN respectively, in predicting IVIG resistance. Despite IVIG administration, 13 of the 287 patients developed CAL. The patients in the CAL group had higher NT-proBNP levels (P<0.01) and higher PMN percentage (P<0.01). In these patients, the results yielded sensitivity (73.3%, 56.7%), specificity (67.9%, 88.9%) and cutoff value (853.4 pg/mL, 80.3%) of NT-proBNP and PMN respectively, for predicting CAL. The area under the curve (AUC) for predicting resistance to IVIG was NT-proBNP 0.712, PMN 0.802. The AUC for predicting CAL was NT-proBNP 0.739, and PMN 0.773.ConclusionSerum NT-proBNP levels and PMN percentage were significantly elevated in patients with KD with IVIG resistance and CAL. Thus, they may be useful predicting markers for IVIG resistance and development of CAL in KD patients.

Effects of erythropoiesis-stimulating agents on heart failure patients with anemia: a meta-analysis.

IntroductionHeart failure (HF) is always complicated with anemia and is associated with bad prognosis in this patient population. Several studies have assessed the potential role of erythropoietin-stimulating agent (ESA) in improving cardiac function and reducing the number of hospitalizations in anemic patients with HF.AimWe performed a meta-analysis to assess the potential role of ESA in the treatment of anemic patients with HF.Material and methodsA literature and Medline search was performed to identify studies with control groups that examined the efficacy of ESA therapy in patients with HF and anemia.ResultsA total of 11 studies were included (n = 3044 subjects) in the final analysis. Compared to placebo, ESA therapy was associated with increased hemoglobin levels (1.89 g/dl; 95% CI: 1.64–2.14, p < 0.00001), increased left ventricular ejection fraction (LVEF) to 6.88 (95% CI: 0.49–13.28, p = 0.03), decreased B-type natriuretic protein (–272.20; 95% CI: (–444.52)–(–99.89), p = 0.002), improvement in New York Heart Association functional class to –0.33 mean difference (95% CI: (–0.44)–(–0.23), p < 0.00001), and decreased hospitalization (OR = 0.61, 95% CI: 0.39–0.94, p = 0.02). There was no significant between-group difference in all-cause mortality (OR = 0.78, 95% CI: 0.51–1.21, p = 0.27).ConclusionsThe treatment of anemia with ESA therapy did not reduce the rate of all-cause mortality among patients with heart failure, but ESA therapy made a potential important contribution to patients’ symptomatic improvement.

Predictive value of circulating N-terminal pro-brain natriuretic protein and VE-catherin in patients with regression of multiple myeloma

Predictive value of circulating N-terminal pro-brain natriuretic protein and VE-catherin in patients with regression of multiple myeloma

Abstract 11682: Prognostic Impact of Periodic Leg Movements in Hospitalized Heart Failure Patients

Background: Periodic leg movements during sleep (PLMs) are the disorder characterized by regularly recurring movements of the legs during sleep. Recently, it has been reported that PLMs have a critical association with cardiovascular mortality and morbidity. However, the prevalence and impact of PLMs on cardiac and all-cause mortality still remain unclear in patients with heart failure (HF). Methods and Results: Consecutive 114 patients admitted for treatment of HF and underwent polysomnography were divided into two groups based on PLM index: moderate-severe PLMs group (PLM index ≥ 20/h, n = 24) and non-mild PLMs group (PLM index &lt; 20/h, n = 90). We compared patient characteristics, findings of echocardiography and cardio-pulmonary exercise test between the two groups. Furthermore, we prospectively followed cardiac events including cardiac death and all-cause mortality. The moderate-severe PLMs group, as compared to non-mild PLMs groups, had lower levels of estimated GFR (46.8 vs. 59.5 ml/min/1.73cm 2 , P = 0.032) and tended to have lower peak VO 2 (14.5 vs. 16.3 ml/min/kg, P = 0.09). In contrast, age, body mass index, systolic blood pressure, B-type natriuretic peptide, hemoglobin, sodium, C-reactive protein and left ventricular ejection fraction were similar between the two groups. Importantly, cardiac mortality (log-rank P = 0.005) and all-cause mortality (P = 0.028) were higher in moderate-severe PLMs group than in non-mild PLMs group (Figure). In the multivariable Cox proportional hazard analyses, after adjusting for potential confounding factors, PLM index was an independent predictor of cardiac (HR 1.024, 95% CI 1.006-1.042, P = 0.009) and all-cause mortality (HR 1.016, 95% CI 1.001-1.031, P = 0.045) in HF patients. Conclusions: The PLM index was a novel predictor of cardiac and all-cause mortality in HF patients.

Abstract 18549: High-sensitivity Troponin I in Stable Patients With Atherosclerotic Disease in the TRA2°P- TIMI 50 Trial

Background: Cardiac troponin I, measured with a high-sensitivity assay (hsTnI), is a well-established prognosticator in patients with acute coronary syndromes. However, its prognostic role in patients with stable atherosclerotic disease, particularly with respect to new or recurrent myocardial infarction (MI), is less defined. Methods: We measured hsTnI (Abbott ARCHITECT) in 19,429 patients with prior MI, ischemic stroke, or symptomatic peripheral arterial disease, who had available baseline samples in the TRA 2°P-TIMI 50 trial of the platelet inhibitor vorapaxar vs. placebo. hsTnI concentration was categorized into 5 groups based on the detection limit (1.9 ng/L), the 99th percentile reference limit (26 ng/L), and tertiles in between (1.9-26 ng/L). The median follow-up was 2.5 years. Sensitivity analyses excluded patients with a history of MI in the prior 30 days and tested sex-specific cutpoints. Results: Higher baseline hsTnI levels were associated with older age, male sex, and an increased burden of atherosclerotic disease. hsTnI identified a graded risk of cardiovascular (CV) death, MI, or stroke with a consistent pattern across each element of this composite, in particular CV death and MI (Figure). This risk relationship was independent of established clinical risk indicators, B-type natriuretic peptide and C-reactive protein (adj-HR 2.17, 95% CI 1.61-2.92 for hsTnI &gt;26 ng/L) and was consistent after excluding pts with recent MI (adj-HR 2.69, 95% CI 1.95-3.71 for hsTnI &gt;26 ng/L). There were no meaningful differences using sex-specific hsTnI cutpoints. The interaction with efficacy of vorapaxar vs. placebo according to hsTnI will be presented. Conclusion: When measured in stable patients with established atherosclerosis, hsTnI concentrations, even below the 99th percentile reference limit, effectively stratified the risk of new or recurrent MI.

Abstract 15901: Radiofrequency Ablation for Persistent Atrial Fibrillation: Earlier Catheter-based Interventions are associated With Better Outcomes and in Direct Association With Markers of Pathways of Atrial Remodeling

Introduction: Persistent atrial fibrillation (PerAF) ablation has been associated with significant recurrence rates which could reflect progressive AF-related atrial remodeling. We hypothesized that the first-diagnosis to ablation time for PerAF is a major determinant of success rates and in direct association with pathways of atrial remodeling. Methods: Two-year outcomes were assessed in 1241 patients undergoing first time ablation of PerAF between January 2005 and December 2012 at our institution. The time intervals between the first diagnosis of PerF and the ablation procedures were determined. Patients had echocardiograms and measures of B-type natriuretic peptide (BNP) and C-reactive protein (CRP) before the ablation procedures. During ablations, patients with atrial scarring by voltage were identified. Results: The median time-to-ablation since the first PerAF diagnosis was 3 years (interquartile range 1-6.5). With longer diagnosis-to-ablation time (based on quartiles), there was a significant increase in BNP levels (p=0.01), CRP levels (p&lt;0.0001), left atrial size (p=0.03) and scarring (p=0.04). Atrial arrhythmia recurred after a single ablation in 555 patients (44.7%); and 364 (29.3%) underwent repeat ablations. At last follow-up, 1005 patients (81.0%, 390 on antiarrhythmic medications) were either arrhythmia free or had their arrhythmia controlled. In Cox Proportional Hazard analyzes, BNP levels, CRP levels, left atrial size and scarring were associated with arrhythmia recurrence. The diagnosis-to-ablation time had the strongest association with success rates which persisted in multivariate Cox analyzes (HR for recurrence per +1Log diagnosis-to-ablation time 1.25, 95%CI 1.11-1.42, p&lt;0.0001; 4th vs. 1st quartile 2.27, 95%CI 1.52-3.47, p&lt;0.0001). Conclusions: The success rates with PerAF ablation are highest with early intervention, that is ablation before the progression of atrial remodeling.

Abstract 12797: A Global Longitudinal Strain in Endocardial Layer Selectively Correlated With Left Ventricular Ejection in Systemic Autoimmune Disorder Patients: A Multi-layer Transthoracic Echocardiography Study

Introduction: In patients with systemic autoimmune disorders (SAD), hemodynamic abnormalities such as pulmonary hypertension occur. Hypothesis: Some specific myocardial characteristics in SAD patients may precipitate hemodynamic abnormalities. Using myocardial multi-layer transthoracic echocardiography (TTE) analysis, we determine left ventricular (LV) myocardial characteristics in SAD patients, and compared LV ejection fraction (LVEF), estimated pulmonary arterial systolic pressure (ePASP) on TTE and serum brain natriuretic protein (BNP). Methods: Twenty SAD patients (18 female; mean age 49±18 years; systemic lupus erythematosus 35%; vasculitis 20%; scleroderma 5%, rheumatoid arthritis 5%, mixed connective tissue disease 5%) underwent TTE (Vivid E9, GE Healthcare). Apical 2-, 3-, and 4-chamber GLS views and parasternal short axis GCS view at the level of the papillary muscle was acquired. GLS was defined by averaging all 17 LV segments. GCS was defined as averaged LV segments at the level of papillary muscle. Furthermore strain measurements (absolute values) of whole, endocardial, and epicardial layers were performed using Echo PAC version 113 (GE Healthcare). Results: There was no significant correlation between GLS (whole, endocardial, and epicardial layers) and LVEF, ePASP, and BNP, respectively. GCS was significantly negatively correlated with serum BNP (R=-0.606 (whole), -0.452 (endocardial) and -0.447 (epicardial layer)). GCS in whole and epicardial layer was significantly negative correlated with ePASP (-0.528 (whole) and -0.457 (epicardial layer)). Only GCS in endocardial layer was significantly positive correlated with LVEF (R=0.466). Conclusions: In SAD patients, GCS significantly correlated with cardiac function and, especially in the endocardial layer selectively and positively correlated with LVEF. These specific myocardial characteristics in SAD patients may precipitate hemodynamic abnormalities.

E-selectin and vascular cell adhesion molecule-1 as biomarkers of 3-month outcome in cerebrovascular diseases.

BackgroundInflammation is known to worsen cerebral damage at the acute phase of stroke. In this setting, cell adhesion molecules (CAMs) play a crucial role mediating migration of immune cells into the infarcted area. However, their value in long-term outcome prediction for patients with cerebrovascular diseases (CVD) is less described.MethodsLevels of four CAMs (E-selectin, P-selectin glycoprotein ligand-1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 (VCAM-1)) and six other known biomarkers (C-reactive protein (CRP), interleukin-6 (IL-6), N-terminal pro-brain natriuretic peptide (NT-proBNP), troponin I, vasopressin-neurophysin 2-copeptin, and S100 calcium-binding protein B) were measured in a population of patients presenting CVD. Blood collections for analysis were performed within different time windows after stroke onset: 0–6 h, 6–36 h, 2–3 days, 5–7 days, and 2–3 weeks. Independent associations with poor outcome at 3 months (modified Rankin Scale score > 2) were sought using univariate and multivariate analysis after adjustments for age and National Institute of Health Stroke Scale score. Predictive ability of each biomarker has also been assessed with ROC analysis.ResultsOne hundred patients were prospectively included whom 75 presented with ischemic strokes, nine with hemorrhagic strokes and 16 with transient ischemic attacks. During the first 6 h after stroke onset, E-selectin was found to be an independent predictor of 3-month outcome (odds ratio (OR) =24; 95 % confidence interval (95 % CI), 2–354; p = 0.022) (area under the curve (AUC) =78 %), as was VCAM-1 during the third week after onset (OR = 8; 95 % CI, 2–37; p = 0.01) (AUC = 73 %). Associations remained after the exclusion of patients with hemorrhagic strokes and transient ischemic attacks. Independent associations with outcome were also found for CRP (OR = 5; 95 % CI, 1–22; p = 0.023) and IL-6 (OR = 5; 95 % CI, 1–17; p = 0.021) at 2–3 days and for NT-proBNP at 6–36 h (OR = 20; 95 % CI, 1–337; p = 0.04).ConclusionsE-selectin and VCAM-1 were independent predictors of outcome in a population of patients with CVD. The predictive capability of other biomarkers known to be indicators for prognosis also emerged, confirming the study’s robustness. CAMs levels could be considered as objective biological criteria for prognosis in CVD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12950-015-0106-z) contains supplementary material, which is available to authorized users.

Editorial: Natriuretic Hormones.

Editorial: Natriuretic Hormones.

Prognostic Role of Hypothyroidism in Heart Failure: A Meta-Analysis.

Hypothyroidism is a risk factor of heart failure (HF) in the general population. However, the relationship between hypothyroidism and clinical outcomes in patients with established HF is still inconclusive.We conducted a systematic review and meta-analysis to clarify the association of hypothyroidism and all-cause mortality as well as cardiac death and/or hospitalization in patients with HF. We searched MEDLINE via PubMed, EMBASE, and Scopus databases for studies of hypothyroidism and clinical outcomes in patients with HF published up to the end of January 2015. Random-effects models were used to estimate summary relative risk (RR) statistics. We included 13 articles that reported RR estimates and 95% confidence intervals (95% CIs) for hypothyroidism with outcomes in patients with HF. For the association of hypothyroidism with all-cause mortality and with cardiac death and/or hospitalization, the pooled RR was 1.44 (95% CI: 1.29–1.61) and 1.37 (95% CI: 1.22–1.55), respectively. However, the association disappeared on adjustment for B-type natriuretic protein level (RR 1.17, 95% CI: 0.90–1.52) and in studies of patients with mean age <65 years (RR 1.23, 95% CI: 0.88–1.76).We found hypothyroidism associated with increased all-cause mortality as well as cardiac death and/or hospitalization in patients with HF. Further diagnostic and therapeutic procedures for hypothyroidism may be needed for patients with HF.

Exercise capacity independently predicts bone mineral density and proximal femoral geometry in patients with acute decompensated heart failure.

Heart failure is associated with increased risk of osteoporosis. We evaluated the prevalence and predictors of osteoporosis in hospitalized patients with ADHF using quantitative computed tomography. Osteoporosis and vertebral fracture are prevalent in patients with ADHF and exercise capacity independently predicts bone mass and femoral bone geometry. Heart failure is associated with reduced bone mass and increased risk of osteoporotic fractures. However, the prevalence and predictors of osteoporosis in hospitalized patients with acute decompensated heart failure (ADHF) are not well understood. Sixty-five patients (15 postmenopausal females and 50 males) with ADHF were prospectively and consecutively enrolled. After stabilization of heart failure symptoms, quantitative computed tomography for bone mineral density (BMD) and femoral geometry as well as biochemical, echocardiographic, and cardiopulmonary exercise tests were performed. Fifteen postmenopausal female showed a high prevalence of osteoporosis (40%) and vertebral fracture (53%). Among 50 male patients, 12% had osteoporosis and 32% had osteopenia, while vertebral fracture was found in 12%. Lumbar volumetric BMD (vBMD) was significantly lower in ischemic patients than non-ischemic patients (107.9 ± 47.5 vs. 145.4 ± 40.9 mg/cm(3), p = 0.005) in male. Exercise capacity, indicated by peak oxygen consumption (VO2), was significantly associated with lumbar vBMD (r = 0.576, p < 0.001) and total hip areal BMD (aBMD) (r = 0.512, p = 0.001) and cortical thickness of the femur neck (r = 0.544, p = 0.001). When controlled for age, body mass index, N-terminal proBrain natriuretic protein (NT-proBNP), etiology of heart failure, hemoglobin, and thigh circumference, multivariate regression analysis revealed peak VO2 independently predicted lumbar vBMD (β = 0.448, p = 0.031), total hip aBMD (β = 0.547, p = 0.021), and cortical thickness of the femur neck (β = 0.590, p = 0.011). In male patients with ADHF, osteoporosis and vertebral fracture are prevalent, and exercise capacity independently predicts bone mass and geometry. Given that heart failure patients with reduced exercise capacity carry a substantial increased risk of fracture, proper osteoporosis evaluation is important in these patients.

Abstract O.39: The Incidence Of Abnormal Electroencephalographic Findings And Mild Encephalitis/encephalopathy With A Reversible Splenial Lesion In Kawasaki Disease

Background: Central nervous system inflammation sometimes occurs in Kawasaki disease (KD). In 2012, we reported the first case of KD complicated with mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in a 14-year-old. Since then, similar cases have been reported. We studied the incidence of KD complicated with encephalitis/encephalopathy and MERS. Methods: We selected 36 patients (22 boys and 14 girls; age: range, 5-80 months; mean, 22 months) from 42 patients who had undergone electroencephalography (EEG) before intravenous immunoglobulin (IVIG) therapy between May 2013 and August 2014. Patients with and without abnormal EEG findings were assigned to groups A and B, respectively. Age; sex; time of diagnosis; neurological symptoms; N-terminal pro-brain natriuretic peptide, serum procalcitonin, serum sodium, serum albumin, and C-reactive protein (CRP) levels; liver disorder, coronary artery lesion, and IVIG therapy response were examined. Results: Group A comprised 6 patients (17%); and group B, 30 patients (83%). Consciousness disturbance was noted in 5 of 6 patients with abnormal EEG findings, without sequelae. Patients in group A were significantly older (56.5±16.8 vs 25.0±19.9 months ) and had higher CRP levels than those in group B (12.3±5.62 vs 6.56±3.47 mg/dL ). No other parameters showed significant differences. Magnetic resonance imaging revealed edema in 2 of 5 patients and MERS in the remaining patient in group A. Pleocytosis was noted in 1 of 4 patients in group A. Cytokine Il-6 and INF-γ levels were very high in the patient with MERS. Conclusion: EEG findings indicating central nerve disorders were noted in 17% patients, a lower incidence than that reported by Mitudome et al . We performed EEG early before IVIG therapy; thus, central nerve symptoms encountered may have occurred in the early stages of the disorders. MERS was noted in 1 of 6 patients with abnormal EEG findings, or 2 of 9 patients if past cases with neurological symptoms were included, suggesting that central nerve complications occur in a certain group of KD patients.

Abstract 27: Elevated Soluble Interleukin 2 Is A Risk Of Treatment Resistance And Coronary Artery Abnormalities In Kawasaki Disease

Background and objective: Soluble ST2 (sST2), an interleukin (IL)-1 receptor family member, has been identified as a novel biomarker for cardiac stress. Although sST2 were reported to be elevated in acute Kawasaki disease (KD) and correlated with cardiac diastolic dysfunction, relation between sST2 levels and treatment resistance and risk of coronary artery abnormalities (CAAs) is not studied. The aim of this study is to evaluate clinical utility of sST2 in acute KD. Methods: We measured serum sST2 from 54 children (median age; 22 months, 29 boys and 26 girls) with acute KD before and after initial treatment, 10 febrile controls (FC) (median age; 14 months) and 2 healthy controls (HC). Using Kobayashi score from RAISE study, patients were divided into high (&gt;score 5)and low risk group (≤score 4) for IVIG resistance. Results: Serum sST2 in KD significantly elevated compared with FC and HC (median; KD vs FC 0.81 vs 0.25 ng/ml, p&lt;0.05, KD vs HC 0.81 vs 0.12 ng/ml, respectively, p&lt;0.05). Compared with sST2 levels before treatment, sST2 decreased at 4 days after initial therapy, but it was not significant (median 0.81 vs 0.67 ng/ml). Statistically significant differences were observed in sST2 between high risk group and low risk group (median; 1.80 vs 0.54 ng/ml, respectively, p&lt;0.05). Additionally, sST2 levels in non-responders to initial treatment were significantly higher than those in responders (median; 1.65 vs 0.64 ng/ml, respectively, p&lt;0.05). There were no significant correlations between sST2 level at diagnosis and plasma brain natriuretic peptide (r = -0.05), C-reactive protein (r = 0.04), and AST (r = 0.07). Overall, 4 children (7%) had CAAs at 4 weeks of illness. sST2 levels at diagnosis were not significantly different between children with and without CAAs, median sST2 levels in children without CAAs (1.68 vs 0.79 ng/ml, respectively, p=0.07). At 4 days after initial therapy, median sST2 levels decreased in children without CAAs, (0.79 vs 0.65, p=0.1), whereas median sST2 levels increased in children with CAAs (1.68 vs 1.70, p=0.9). Conclusions: Elevated sST2 may be a potential risk factor of initial treatment resistance and developing CAAs in acute KD.

Transfusion-associated circulatory overload (TACO): prevention, management, and patient outcomes

Transfusion-associated circulatory overload (TACO): prevention, management, and patient outcomes Nareg H Roubinian,1,2 Edward L Murphy1&ndash;3 1Blood Systems Research Institute, 2Department of Laboratory Medicine, 3Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA Abstract: Transfusion-associated circulatory overload (TACO) is acute pulmonary edema associated with left atrial hypertension or volume overload occurring within 6 hours following a blood transfusion. Recognized by physicians as a common complication of blood transfusion, its incidence has been difficult to measure because active surveillance is required to counteract underreporting; active surveillance indicates overall incidence rates as high as 1% per transfused patient. Recent clinical and translational research has focused on the development of electronic alert systems to measure TACO incidence and provide alerts to physicians regarding patients at high risk. Translational research regarding the utility of biomarkers such as brain natriuretic protein (BNP) or N-terminal pro-BNP (NT-proBNP) as diagnostic tools for TACO has been only moderately successful, but the search for other biomarkers continues. Prevention strategies can be developed based upon evidence derived from both observational studies and might include: using documented risk factors to highlight patients at risk, preferably using real-time analysis of electronic medical records; implementation of modified transfusion strategies to minimize the volume and infusion rate of blood products; consideration of prophylactic diuretic therapy; and heightened diagnostic awareness combined with rapid implementation of treatment. Randomized clinical trials will be required to test such strategies before they are widely implemented. Finally, the occurrence of TACO ought to be considered as a potentially avoidable medical complication that could be used to benchmark transfusion and critical care practice across hospitals. Keywords: blood transfusion, pulmonary edema, risk factors, prevention and control, therapeutics

Men born in 1913 followed to age 100 years

Objectives. To examine causes of death for men above 80 years of age, and health status in centenarians in a cohort of men followed from age 50 years. Factors of importance for survival were studied. Design. A representative sample of men born in 1913 was first examined in 1963 and re-examined at ages 54, 60, 67, 75, 80 and 100 years. Results. Of 973 selected men, 855 (88%) were examined at age 50, and 10 were alive at age 100.Twenty-seven percent lived until 80 years. Cardiovascular disease was the most common cause of death after this age. Dementia was recorded in two of ten men at age 100. Long survival was related to the mothers' high age at death, to non-smoking, high social class at age 50 and high maximum working capacity at age 54 years. At age 100, the seven examined men had low/normal blood pressure. Serum values of troponin T, N-terminal pro-brain natriuretic peptides and C-reactive protein were elevated, but echocardiographic findings were normal. Conclusions. Ten men experienced their 100th birthday. Survival was related to non-smoking, mothers' high age at death, high social class and previous high physical working capacity. Age-adjusted reference levels for laboratory tests are needed for centenarians.