bluuebunny/crossref_metadata_2025 huggingface dataset:
Creatine measurement in serum and urine with an automated enzymatic method
Authors: Beyer C
Published: January 2020

I describe an automated enzymatic procedure to quantitate creatine in both serum and urine. In this assay, which requires no pretreatment of the sample, creatine kinase (CK; EC 2.7.3.2) and pyruvate kinase (EC 2.1.7.40) are used as auxiliary enzymes and lactate dehydrogenase (EC 1.1.1.27) is used in the indicator reaction. CK is also used as the starting reagent. Data obtained with the present method for creatine measurement in serum were compared with those from the Jaffé method and an enzymatic method: y = 1.13x - 7.58, SE = 4.48, and r = 0.925 (Jaffé); and y = 1.17x + 2.73, SE = 5.06, and r = 0.962 (enzymatic); for creatine measurement in urine: y = 0.63x + 39.74, SE = 296.7 and r = 0.719 (Jaffé). The present method provides improved precision: the total CVs for serum, determined by the present and comparative methods, respectively, were 3.5-8.9%, 8.2-43.0%, and 5.3-16%; for urine, the CVs were 3.3-5.1% and 9.6-21.2% for the present and comparative method, respectively. I established the normal reference interval as 13-74 and 13-89 mumol/L for creatine in serum, and as 175-700 and 150-1200 mumol/24 h for creatine in urine for men and women, respectively.
Europium-labeled oligonucleotides to detect point mutations: application to PIZ alpha 1-antitrypsin deficiency
Authors: Dahlén P , Carlson J , Liukkonen L , Lilja H , Siitari H , Hurskainen P , Iitä A , Jeppsson J O , Lövgren T
Published: January 2020

We describe a novel assay for detection of point mutations. The method combines the specificity and sensitivity of the polymerase chain reaction (PCR) and allele-specific oligonucleotides (ASO) with highly sensitive time-resolved fluorometry. ASO probes differing by a single base substitution and labeled with europium (Eu) chelates were hybridized in solution simultaneously with a biotinylated oligomer to a PCR-amplified nucleic acid fragment. The hybrids formed were then collected onto streptavidin-coated microtitration wells. Subsequently, the hybrids were washed under stringent conditions and the remaining ASO probe was measured in a time-resolved fluorometer. We discuss the strategy underlying the design of the Eu-labeled ASO probes for the solution hybridization assay. The method was applied to the detection of the Z-mutation in the alpha 1-antitrypsin gene. Evaluation of whole-blood samples spotted on Guthrie cards demonstrated successful accuracy of the method.
Trace elements determined along single strands of hair by inductively coupled plasma mass spectrometry
Authors: Yoshinaga J , Shibata Y , Morita M
Published: January 2020

Flow injection-inductively coupled plasma mass spectrometry has been evaluated for determining the distribution profile of trace elements along a single strand of hair. Hair was cut into several mm long sections from follicle to the distal end. Each section was solubilized in a capped 1.5-mL polypropylene tube with small volume of nitric acid (typically 50 microL) at room temperature. After dilution an aliquot (50 microL) was introduced into the mass spectrometer by flow injection. The limit of determination was typically 5-50 pg with 5-10% precision (CV), depending on the element examined; this corresponds to sub-microgram/g concentrations of these elements in hair segments. Recent exposure and intake history of individuals to thallium or mercury could be reconstructed by this system.
Determination of inorganic arsenic and its organic metabolites in urine by flow-injection hydride generation atomic absorption spectrometry
Authors: Hanna C P , Tyson J F , McIntosh S
Published: January 2020

A method has been developed for the determination of inorganic arsenic [As(III) and As(V)] and its organic metabolites (monomethylarsenic and dimethylarsenic) in urine by flow-injection hydride generation atomic absorption spectrometry. The nontoxic seafood-derived arsenobetaine and arsenocholine species were first separated by a solid-phase extraction procedure. The remaining sample was digested with a mixture of nitric and sulfuric acids and potassium dichromate, followed by attack with hydrogen peroxide. The resulting As(V) was reduced to As(III) with potassium iodide in hydrochloric acid before injection into the flow-injection manifold. The percentage analytical recoveries (mean +/- 95% confidence interval) of various arsenic species added to a urine specimen at 250 micrograms/L were 108 +/- 2, 112 +/- 11, 104 +/- 7, and 95 +/- 5 for As(III), As(V), monomethylarsenic, and dimethylarsenic, respectively. For the determination of arsenic in Standard Reference Material 2670 (toxic metals in human urine), results agreed with the certified value (480 +/- 100 micrograms/L). Analyses of samples for the Centre de Toxicologie du Quebec, containing seafood-derived species, demonstrated the viability of the separation procedure. Detection limits were between 0.1 and 0.2 microgram/L in the solution injected into the manifold, and precision at 10 micrograms/L was between 2% and 3% (CV). These preliminary results show that the method might be applicable to determinations of arsenic in a range of clinical urine specimens.
Platelet-poor plasma serotonin in normal and preeclamptic pregnancy
Authors: Middelkoop C M , Dekker G A , Kraayenbrink A A , Popp-Snijders C
Published: January 2020

We determined serotonin concentrations in platelet-poor plasma (PPP) from 11 preeclamptic pregnant women and 11 normal pregnant women by HPLC with electrochemical detection after a concentration step. Serotonin concentrations in PPP are very low in comparison with those in platelets, so it is very important to avoid in vitro release of serotonin from platelets. We therefore investigated three types of anticoagulants, the method of blood sampling, and the influence of whether the first or second 10 mL of blood is assayed. The type of anticoagulant proved to be important, K3-EDTA giving the best results. The serotonin concentrations in PPP from the preeclamptic pregnant women were significantly higher (P = 0.0001) than in the normal pregnant women: mean values +/- SD were 27.0 +/- 13.5 and 2.8 +/- 1.4 nmol/L, respectively. We suggest that the measurement of serotonin in PPP might be helpful in study of the role of serotonin in the development of preeclampsia.
Latex agglutination test for detecting antibodies to Treponema pallidum
Authors: Matsumoto M , Ishikawa F , Matsubayashi T , Nagao T , Inuzumi K , Araki H , Kawai K , Osato K
Published: January 2020

We have developed an automated latex agglutination test for Treponema pallidum (TPLA) for measurement of the concentration of treponemal antibodies in syphilitic sera. The assay needs neither a complicated pretreatment of the sera nor special techniques. Intra- and interassay precision studies showed high reproducibility. Potentially interfering substances, such as bilirubin, hemoglobin, triglycerides, and rheumatoid factor, did not affect the results. The results obtained with the TPLA test showed a strong correlation with those from conventional methods. This test for antibodies to T. pallidum may be useful for the mass screening of syphilitic infections.
Interference of polyclonal free light chains with identification of Bence Jones proteins
Authors: Hess P P , Mastropaolo W , Thompson G D , Levinson S S
Published: January 2020

We present a case in which kappa free light chains caused difficulty in interpreting classical urinary immunoelectrophoresis, but immunofixation electrophoresis (IFE) demonstrated the presence of a lambda-Bence Jones protein. Analysis of the urine by Ouchterlony double diffusion and IFE after gel-filtration chromatography showed that the difficulty was caused by the presence of large amounts of polyclonal free light chains. The workup also demonstrated that although IFE is the more sensitive and specific technique, IFE performed on concentrated urinary samples is especially subject to misinterpretation unless densely staining patterns are diluted and reassayed. This process of sample dilution provides a means for titrating antigen and antibody concentrations such that condition-specific patterns become visible on the gel. This workup also shows that, at some dilutions, polyclonal free light chains may migrate in the same manner as an oligoclonal band in a so-called ladder configuration. These bands were observed from both monomeric and dimeric fractions isolated by gel chromatography, consistent with reports that this pattern is largely linked to the isoelectric points of the molecules. We speculate that, in rare instances, the distinction between polyclonal and monoclonal kappa free light chains migrating as a ladder-banding pattern may be equivocal.
Urinary trans,trans-muconic acid determined by liquid chromatography: application in biological monitoring of benzene exposure
Authors: Lee B L , New A L , Kok P W , Ong H Y , Shi C Y , Ong C N
Published: January 2020

We describe a sensitive and specific high-performance liquid-chromatographic method for determining the benzene metabolite, trans,trans-muconic acid (ttMA) in urine by measuring ultraviolet absorbance at 265 nm. We mix 1 mL of urine sample with 2 mL of Tris buffer containing vanillic acid as internal standard (IS) and percolate this through a preconditioned ion-exchange column. After rinsing the column with phosphoric acid solution, acetate buffer, and deionized water, we elute the analytes with 2 mL of an equivolume solution of 1.5 mol/L sodium chloride and methanol. Of this, 5 microL is injected into the HPLC column. The mobile phase used consists of, per liter, 10 mL of acetic acid, 100 mL of methanol, and the rest 5 mmol/L sodium acetate. The flow rate was started at 1 mL/min and increased to 1.5 mL/min after 6 min. ttMA and IS were detected at 5.2 and 10.2 min, respectively. The lowest detection limit is 125 pg. Analytical recovery and reproducibility generally exceeded 90%. We validated the method with urine samples collected from normal persons and from refinery workers exposed to benzene concentrations < 1 microL/L. The results show that urinary ttMA is a promising biological marker for risk assessment of low-concentration benzene exposure.
Quantitative measurement of duplicated DNA as a diagnostic test for Charcot-Marie-Tooth disease type 1a
Authors: Hensels G W , Janssen E A , Hoogendijk J E , Valentijn L J , Baas F , Bolhuis P A
Published: January 2020

Charcot-Marie-Tooth disease type 1 (CMT1) is a hereditary motor and sensory neuropathy. The autosomal dominant subtype is often linked with a large duplication on chromosome 17p11.2. The gene encoding the peripheral myelin protein PMP 22 (the critical gene in this subtype of CMT1) is located within this duplication. To detect this duplication in chromosomal DNA from individuals thought to have CMT1, we compared the hybridization signals of two DNA probes within this duplication (VAW412R3a and VAW409R3a) with the signal of a reference probe (E3.9). When duplication was present, the signals from the first two probes increased from 100% (for nonduplicated samples) to 145% and 142%, respectively. The day-to-day variance was 3.7% and 5.1%, respectively. We demonstrated this DNA duplication in 49 of 95 DNA samples from unrelated individuals thought to have CMT1. Moreover, because hereditary neuropathy with liability to pressure palsies (HNPP) is based on a DNA deletion in the same area of chromosome 17, this quantitative test may be useful in establishing the presence of HNPP. In a preliminary investigation, four unrelated patients with HNPP yielded test values of 63% and 54%, respectively, of those for nonduplicated samples (CV 19% and 18%, respectively; n = 4), suggesting a deletion in 17p11.2.
Sandwich enzyme immunoassay of cystatin C in serum with commercially available antibodies
Authors: Pergande M , Jung K
Published: January 2020

We developed a sandwich enzyme immunoassay for determining cystatin C in serum by using commercially available antibodies. We optimized each assay step (e.g., concentrations of coating rabbit anti-human cystatin C antibodies and horseradish peroxidase-conjugated antibodies) and studied the binding kinetics of antigen and antibodies. The within-assay CV was < 5%, the between-assay CV was 8.8%, the detection limit was 0.9 microgram/L, and the assay can be performed within 2 h. Cystatin C concentrations in sera from men were significantly higher than in women (mean and SD: 2.14 +/- 0.31 vs 1.78 +/- 0.26 mg/L). We studied the cystatin C concentrations in sera of 31 outpatients with suspected kidney damages to characterize the behavior of this low-M(r) protein as a possible indicator for estimating the glomerular filtration rate. The correlation with the values obtained by a standard isotopic method involving 99mTc-diethylenetriaminopentaacetic acid was rs = -0.89. The diagnostic sensitivity of cystatin C was 88.2% of that of the standard isotope clearance method and better than those of the conventional serum indicators of reduced kidney function, beta 2-microglobulin (64.7%) and creatinine (52.9%).
Performance of Gem Premier blood gas/electrolyte analyzer evaluated
Authors: Jacobs E , Nowakowski M , Colman N
Published: January 2020

We evaluated a new analyzer designed for point-of-care testing of blood gases, sodium, potassium, ionized calcium, and hematocrit. The Gem Premier (Mallinckrodt) system has two components: the analyzer and a disposable cartridge. Analysis takes place in the cartridge, which contains the electrochemical sensors, the calibrants, the reagents, the sampling stylus, and the waste container. The system was evaluated for imprecision and accuracy. With aqueous control materials, total imprecision (CV) was: pH, 0.10-0.18%; PCO2, 3.16-5.78%; PO2, 2.92-4.85%; sodium, 0.82-1.44%; potassium, 1.35-1.48%; ionized calcium, 0.75-1.45%; and hematocrit, 1.13-1.83%. Accuracy of the system was assessed by split-sample comparison with the Radiometer ABL 330 blood gas analyzer for pH and blood gases, the Nova Stat Profile 5 for whole-blood electrolyte and hematocrit analysis, and the IL Phoenix for plasma electrolyte analysis. After outlier correction, regression statistics were excellent for all analytes except sodium, which demonstrated Sy[x values between 1.80 and 2.30 mmol/L and 0.85 < or = r < 0.90.
A reference preparation of creatine kinase BB isoenzyme
Authors: Mathieu M , Steghens J P , Hørder M , Moss D W , Colinet E , Profilis C
Published: January 2020

Creatine kinase (CK; EC 2.7.3.2) catalytic activity in serum is widely measured in clinical chemistry practice and provides information for diagnosis and follow-up in many pathological conditions affecting heart, muscle, and brain. Depending on the organ involved, the predominant CK isoenzyme in serum varies. However, routine methods measure total CK catalytic activity, and standardized methods for doing so have been recommended by the International Federation of Clinical Chemistry and by several national scientific societies. Many commercial kits for those methods are now available. With use of a reference material for CK, commercial reagents can be compared with standardized methods, improving confidence in the results. Here we present a reference preparation of CK consisting of the BB isoenzyme purified from human placentae. We describe the procedure of purification and the properties of the lyophilized preparation of CK-BB, which has been certified by the Community Bureau of Reference of the Commission of the European Communities under the designation CRM 299. The preparation can be used to calibrate assays of the catalytic activity of CK-MM and CK-MB, as well as CK-BB.
Evaluation of laboratory data by conventional statistics and by three types of neural networks
Authors: Schweiger C R , Soeregi G , Spitzauer S , Maenner G , Pohl A L
Published: January 2020

Sixty-three patients with lung (34 small-cell, 18 squamous, 11 adeno-) carcinomas and 43 patients with benign lung diseases were characterized with seven tumor markers: neuron-specific enolase (NSE); cancer antigens CA 19-9, CA 125, CA 15-3, and CA 50; carcinoembryonic antigen (CEA); and tissue polypeptide antigen. Diagnosis had been established by histological examination after surgery and used for classification. After vector transformation, the tumor marker data were fed into neural networks (NNs) based on three different types of learning algorithms: backpropagation (BP), competitive learning (CL), and Hopfield (H). For comparison, the data were evaluated with multivariate stepwise discriminant analysis (MVSDA). BP-NNs are equal to (NSE, CA 19-9, CEA) or better than (100% correct classification when using all seven markers) MVSDA in assigning the correct diagnosis to the patients. Cross-validation data yielded shrinkage effects ranging from 0% to 12.5%. Quality-control (QC) data were evaluated by traditional QC algorithms and compared with the results obtained by a BP-NN. The results show that the BP-NNs could only partly fulfill the tasks of three QC algorithms regarding the violation of static borders but gave good results with respect to dynamic changes.
Genetic algorithms-based design and optimization of statistical quality-control procedures
Authors: Hatjimihail A T
Published: January 2020

In general, one cannot use algebraic or enumerative methods to optimize a quality-control (QC) procedure for detecting the total allowable analytical error with a stated probability with the minimum probability for false rejection. Genetic algorithms (GAs) offer an alternative, as they do not require knowledge of the objective function to be optimized and can search through large parameter spaces quickly. To explore the application of GAs in statistical QC, I developed two interactive computer programs based on the deterministic crowding genetic algorithm. Given an analytical process, the program "Optimize" optimizes a user-defined QC procedure, whereas the program "Design" designs a novel optimized QC procedure. The programs search through the parameter space and find the optimal or near-optimal solution. The possible solutions of the optimization problem are evaluated with computer simulation.
62 Time course of improvement in secretory unbalance of asymmetric dimethylarginine and nitric oxide productions in response to exercise training in middle-aged and older adults
Authors: Fujie S , Hasegawa N , Sanada K , Hamaoka T , Maeda S , Iemitsu M
Published: January 2020

Funding Acknowledgements

Supported by Grants-in-Aid for Scientific Research (#17H02182, #16K13059, M. Iemitsu; #18J01024, S. Fujie)

Introduction

Aging is well known to elevate risks of cardiovascular diseases. As a mechanism of these increased risks with aging, a reduction of nitric oxide (NO) production via augmented secretion of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthesis is related. Habitual aerobic exercise has shown to improve secretory unbalance of endothelium-derived regulating factors with aging, such as increase in NO and decrease in ADMA, resulting in the reduction of arterial stiffness. However, the time course of improvement in secretory unbalance of NO and ADMA productions in response to exercise training in middle-aged and older adults remains unclear.

Purpose

This study aimed to determine the time course of changes in plasma nitrite/nitrate (NOx) and ADMA levels related to exercise-training effects of arterial stiffness in healthy middle-aged and older adults.

Methods

Thirty-two Japanese healthy middle-aged and older subjects (67 ± 1 years) were randomly divided into two groups: exercise intervention and sedentary controls. Subjects in the training group completed 8-week of aerobic exercise training (60-70% peak oxygen uptake [VO2peak] for 45 min, 3 days/week). We evaluated plasma NOx and ADMA concentrations and carotid-femoral pulse wave velocity (cfPWV) as an index of arterial stiffness, measured every 2 weeks for 8-week in the training group.

Results

cfPWV was gradually declined from baseline to 8-week and significantly decreased from baseline at weeks 6 (P < 0.05) and 8 (P < 0.01). Plasma NOx level was gradually elevated during exercise intervention and significantly increased from baseline at weeks 6 (P < 0.05) and 8 (P < 0.01). Interestingly, plasma ADMA level was significantly decreased at 8-week intervention (P < 0.05). Furthermore, the exercise training-induced reduction in plasma ADMA level was negatively correlated with the change in plasma NOx level before and after the 8-week (r = -0.483, P < 0.05). The exercise training-induced change in plasma ADMA concentration was positively correlated with training-induced change in cfPWV before and after the 8-week (r = 0.633, P < 0.01). Additionally, there was a negative correlation between the changes in plasma NOx level and cfPWV before and after the 8-week (r = -0.642, P < 0.05).

Conclusions

These results suggest that habitual aerobic exercise can normalize the secretory unbalance of NO and ADMA productions in 6 to 8 weeks, and these balance normalizations may be contributed to the reduction of arterial stiffness in the middle-aged and older adults.
64 Biomarker-based index for detecting sarcopenia in patients with cardiovascular disease
Authors: Kai H , Harada H , Niiyama N , Katoh A
Published: January 2020

Background

Clinical significance of sarcopenia has been highlighted in patients with cardiovascular disease (CVD). Sarcopenia is generally diagnosed based on the decrease in skeletal muscle index (SMI) and the reduction of either handgrip strength or gait speed. However, SMI is difficult to measure for general physicians or cardiologists, because special, expensive equipment (i.e. bioelectrical impedance assay (BIA) or dual-energy X-ray absorptiometry) is necessary.

Purpose

The aim of this study was to seek a new, simple index to detect sarcopenia in CVD patients.

Methods

We retrospectively investigated the association of sarcopenia with physical examination data and circulating biomarkers of nutrition, inflammation, skeletal muscle homeostasis in 132 CVD patients who admitted in our hospital. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia (AWGS) guidelines using SMI measurements by BIA method.

Results

Among the screened biomarkers (e.g. hsCRP and IL-6), serum adiponectin and sialic acid was significantly higher in sarcopenic patients (n = 39) than non-sarcopenic patients (n = 93). On stepwise multivariate regression analysis, adiponectin, sialic acid, sex, age, and body mass index were independent detecting factors for sarcopenia based on AWGS criteria. ROC curve analysis revealed high accuracy for sarcopenia detection of the biomarker-based sarcopenia index (BMI), obtained from the regression formula using the independent factors (Figure). Conclusions: Novel biomarker-based sarcopenia index would be a simple, useful tool for detecting sarcopenia in CVD patients.

Abstract 64 Figure. Sarcopenia Detection using BSI
223 Association of levels of IL-6, IL-10, IL-18 and TNF-alpha with rheumatic mitral stenosis and subsequent pulmonary hypertension
Authors: Tripathi GAURAV , Tyagi SANJAY , Mahajan BHAWNA , Mehta VIMAL
Published: January 2020

Background

Rheumatic heart disease (RHD) remains a serious public health problem in developing countries. The pattern of immune response after exposure to streptococcal infection is one of the main determinants of the rheumatic inflammatory process, making it essential to identify the patients who have a higher risk of disease progression.

Objective

To give an insight into the pathophysiology of the rheumatic afflicted valves and the role of IL-6, IL-10, IL-18 and TNF-α in the different stages of RHD. 

Methods

 The study included 84 consecutive patients (62 females, mean age 34.6 ± 10.6 years) with symptomatic, severe chronic rheumatic mitral stenosis (Group-A). 79 age and gender matched normal healthy volunteers were enrolled as controls (Group-B). Patients with chronic rheumatic mitral stenosis were further divided into subgroups based on severity of mitral stenosis [MVA ≤ 1 cm2 (Subgroup Aa) and MVA > 1 cm2 (Subgroups Ab)] and presence or absence of pulmonary hypertension [RVSP ≥ 36 mm Hg (Subgroup Ac) and RVSP < 36 mm Hg (Subgroup Ad)]. IL-6, IL-10, IL-18, TNF-α and hs-CRP levels were assessed in both groups.

Results

The mean serum levels of IL-6, IL-10, IL-18, TNF-α and hs-CRP in Group-A and Group-B were 6.57 ± 3.53 pg/mL and 2.73 ± 1.01 pg/mL (p <0.001), 8.19 ± 2.80 pg/mL and 3.51 ± 0.86 pg/mL (p  <0.001), 136.31 ± 89.02 pg/mL and 47.96 ± 9.76 pg/mL (p <0.001), 21.26 ± 18.59 pg/mL and 5.36 ± 3.57 pg/mL (p <0.001), 4.69 ± 6.31 pg/mL and 2.63 ± 2.22 pg/mL (p <0.008) respectively. On subgroup analysis mean TNF-α in subgroup Aa was 20.71 ± 16.84 pg/mL, while in subgroup Ab it was 7.56 ± 1.93 pg/mL (p <0.001). Mean IL-10 in subgroup Ac and Ad was 8.74 ± 3.29 pg/mL and 7.47 ± 1.82 pg/mL respectively (p <0.028).

Conclusions

Chronic rheumatic mitral stenosis patients have increased IL-6, IL-10, IL-18, TNF-α and hs-CRP levels suggesting a continuous ongoing inflammatory activity even in chronic phase. Further subjects having severe mitral stenosis had increased TNF-α levels in comparison to subjects with mild to moderate mitral stenosis suggesting its possible role in acceleration of rheumatic process.

Cytokines in various subgroup Parameter IL-6 (pg/ml) p IL-10 (pg/ml) p IL-18 (pg/ml) p TNF-α (pg/ml) p hs-CRP (pg/ml) p Subgroup Aa 5.63 ± 3.25 0.13 8.38 ± 3.06 0.32 146.35 ± 103.84 0.20 20.71 ± 16.84 <0.001 3.72 ± 3.43 0.67 Subgroup Ab 6.90 ± 3.57 7.72 ± 2.04 112.28 ± 22.79 7.56 ± 1.93 4.27 ± 3.81 Subgroup Ac 6.86 ± 3.50 0.44 8.74 ± 3.29 0.02 145.29 ± 103.01 0.29 20.25 ± 17.02 0.53 4.77 ± 0.93 0.93 Subgroup Ad 6.21 ± 3.49 7.47 ± 1.82 124.67 ± 66.95 22.91 ± 20.68 4.66 ± 3.44

Abstract 223 Figure. Cytokines in case and control
225 Rheumatic heart disease in Timor Leste school students (RHD-TL) follow-up study: assessment of secondary prophylaxis and outcomes in Timor Leste
Authors: Horton A , Remenyi B , Davis K , Mock N , Paratz E , Harries J , Dos Santos J A , Francis J R
Published: January 2020

Background

The Rheumatic Heart disease in Timor Leste school students (RHD-TL) study identified Timor Leste as having some of the highest rates of definite rheumatic heart disease (RHD) in the world. The RHD-TL follow-up study aimed to assess the delivery and outcomes of the secondary prophylaxis program in known patients with echocardiographic screen detected definite and borderline RHD.

Methods

School-students in Timor Leste where reassessed over a 3-year period since the initial study in 2016. Prospective assessments included adherence to secondary prophylaxis, complications of prophylaxis, follow-up clinical assessment and serial echocardiography. Of the 48 patients, 25 Definite and 23 Borderline, 38 (79%) of all patients, and 92% of definite RHD cases have had one or more follow-up assessments including full datasets for adherence, recurrence rates and progression of disease. Follow-up is provided by the volunteer paediatric cardiology team and rheumatic heart disease team of two NGOs in collaboration with local clinics.

Results

The median duration of follow-up of the 38 patients was of 1.6 years. The median age was 13 years (range 8-22) and 75% were female. Adherence rates in patients with definite RHD was on average greater than 95% during the follow-up period. Of the 23 patients with mild or moderate RHD one case with documented acute rheumatic fever (ARF) recurrence progressed whilst 8 cases improved on benzathine-penicillin G (BPG) therapy. There was no progression of the 6 borderline cases who were not prescribed BPG. Out of the 9 borderline cases in whom BPG was prescribed, one, with 67% adherence, had a documented episode of ARF leading to echocardiographic progression and moderate definite RHD.

Conclusion

This was the first follow-up study to look at disease natural history, both in treated and untreated groups, in Timor-Leste and brought practical insights into the efficacy of the Timor Leste RHD monitoring and prophylaxis programs. Its ongoing project will enable advocacy and quality assessment for the program as it expands.

Abstract 225 Figure 1.
P6 Characterisation of right heart dysfunction in left ventricular systolic failure
Authors: Chen H H L , Gan C H , Makarious D , Ng C H , Bhat A , Khanna S , Tan T C
Published: January 2020

Funding Acknowledgements

Nil

Background

Left and right ventricular (RV) function is proposed to be intimately linked. Reduced systolic ventricular interaction in patients with reduced global left ventricular (LV) performance is hypothesised to result in a reduction in RV contractile performance, even if the RV is not directly involved in the disease process. Concurrent RV and LV dysfunction is known to carry a poorer prognosis. However, the incidence of RV structural change and systolic dysfunction in patients with LV dysfunction in patients in a clinical setting is not well characterised.

Purpose

To determine the prevalence of RV systolic impairment in patients with LV systolic impairment from non-ischaemic cardiomyopathy (NICM); and to characterise the relationship between LV and RV systolic function using echocardiographic parameters.

Methods

86 consecutive patients with stable heart failure with reduced ejection fraction secondary to NICM without valvular, congenital, and pulmonary disease were recruited. All patients underwent a comprehensive transthoracic echocardiogram and were stratified into tertiles based on LVEF (mild: 40-49%, moderate: 30-39%, severe: <30%). RV function was characterised using standard and novel measures. 2D RV free wall peak systolic strain (RV FWS) was measured using vendor independent software (TomTec Image Arena, Germany v4.6). 

Results

Of the mild, moderate and severe groups (mean age 58 ± 34, 36% men): mean LVEF (%) was 46 ± 6, 35 ± 6, 22 ± 10 ; mean pulmonary artery systolic pressure (mmHg) was 28 ± 24, 34 ± 31, 38 ± 24; 26%, 79%, 74% had mild or moderate pulmonary hypertension respectively. 33% had RV impairment based on TAPSE of <1.6cm; 48% had RV impairment based on RVS’ of <10cm/s; and 65% had RV impairment based on a FAC of <35%. 

Conclusion

Whilst there is a concurrent increase in the prevalence of RV impairment with severity of LV systolic impairment, interestingly not all patients with LV dysfunction had RV dysfunction. The presence of RV dysfunction is greatest when measured using FAC and RV FWS. Routine screening of RV dysfunction in patients with HFrEF secondary to NICM may help identify patients with poorer prognosis, who could benefit with more intensive follow up and treatment.

LVEF 40-49% (n = 31) LVEF 30-39% (n = 28) LVEF < 30% (n = 27) ONE WAY ANOVA Significance (P value) Mean RV Basal Diameter (cm) 4.1 ± 1.3 3.7 ± 1.6 3.6 ± 1.5 0.51 Mean TAPSE (cm) 2.1 ± 0.8 1.9 ± 1.0 1.7 ± 1.1 0.49 Mean RVS" (cm/s) 11 ± 5 11 ± 6 9 ± 6 0.24 Mean FAC (%) 44 ± 20 29 ± 21 17 ± 13 0.000 Mean RV FWS (%) -27.4 ± 14.4 -17.2 ± 11.6 -7.9 ± 6 0.000
P11 The difference in the serial change of indoxyl sulfate after catheter ablation among atrial fibrillation patients with or without chronic kidney disease
Authors: Koike H , Watanabe I , Akitsu KATSUYA , Shinohara MASAYA , Kinoshita TOSHIO , Yuzawa HITOMI , Suzuki TAKEYA , Fujino TADASHI , Morita TOSHISUK , Ikeda TAKANORI
Published: January 2020

Introduction

It is well known that catheter ablation (CA) for patients with atrial fibrillation (AF) improves their renal function. However, the precise mechanism of improving a renal function, such as a transition of the uremic toxin is unclear.

Purpose

Indoxyl sulfate (IS), a protein-bound uremic toxin, induces chronic kidney disease (CKD) and AF. This study aimed to investigate the transition of serum IS level in the AF patients with and without CKD after CA.

Methods

A total of 138 consecutive AF patients who underwent CA and maintained sinus rhythm were prospectively enrolled (age 65.5 ± 10.7 years, paroxysmal AF 67.4%). Patients were divided into 4 groups (non-CKD/low-IS:68, non-CKD/high-IS:28, CKD/low-IS:13, CKD/high-IS:29). CKD was defined as CKD stage III (estimated glomerular filtration rate (eGFR) 30-60 ml/min/1.73m2), and high-IS was defined according to the mean of IS (IS≥1.1 μg/ml) before CA. Plasma IS levels and eGFR were determined before and at 1 year after CA. We evaluated the relationship between the IS and eGFR after CA among the 4 groups.

Results

CA significantly improved the eGFR in patients with CKD (from 50.2 ± 5.7 to 55.4 ± 10.8 ml/min/1.73m2, p < 0.001). The serum IS level in the patients with non-CKD/high-IS was significantly decreased (from 1.7 ± 0.7 to 1.1 ± 0.6 μg/ml, p < 0.001). However, the serum IS level in the patients with CKD/high-IS was not improved (from 1.9 ± 0.9 to 1.7 ± 0.7 μg/ml, p = 0.22) and significantly higher than that in the others (p < 0.001), regardless of improving their eGFR (Figure). Furthermore, the multiple regression analysis revealed that the ΔIS, between before and after CA, was independent of eGFR.

Conclusion

The change of IS in the patients with CKD was significantly different from that in those without CKD. In the patients with CKD, CA improved their eGFR, however, the serum level of IS, a protein-bound uremic toxin, was not improved after CA.

Abstract P11 Figure. Serial Change of eGFR and IS
P16 Relationship of plasma long Pentraxin-3 concentration with clinical and angiographic outcomes of patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary
Authors: Sari N Y , Dharma S , Sukmawan R , Dakota I , Rao S V
Published: January 2020

Background

Inflammation has an important role for the progression of coronary plaque vulnerability to acute coronary thrombosis. Long pentraxin-3 (PTX3) is a sensitive marker of inflammation released upon exposure to primary inflammatory signals. Whether concentration of PTX3 affects coronary thrombus severity and impaired coronary flow in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is unknown.

Purpose

This study sought to evaluate the relationship of plasma PTX3 concentration with coronary thrombus severity and final TIMI flow after primary PCI in patients with acute STEMI.

Methods

We prospectively enrolled 335 consecutive patients with acute STEMI undergoing primary PCI between 1 January 2018 and 2 August 2018. Plasma PTX3 concentrations were measured at admission by ELISA method. 

Results

Compared to low PTX3 group (<0.33 ng/mL; N = 223), patients in the high PTX3 group (≥ 0.33 ng/mL; N = 112) had higher proportion of thrombus grade 4 and 5 on initial coronary angiogram (83% vs. 72%, p= 0.03), final TIMI flow <3 (66% vs. 51%, p= 0.01), incomplete ST segment resolution after primary PCI (85% vs. 72%, p= 0.002) and Killip classification II-IV at entry (34.8% vs. 13%, adjusted odds ratio= 3.38, p< 0.001). High PTX3 concentration was associated with an increased risk of 30-day mortality (adjusted hazard ratio= 3.41, 95% confidence interval, 1.27 to 9.11, p= 0.01). 

Conclusion

High plasma PTX3 concentration is associated with worse clinical and angiographic outcomes among patients undergoing primary PCI for STEMI. Further study is needed to eludicate whether PTX3 is a causal agent for adverse outcomes and whether therapies directed at reducing PTX3 levels are effective.

Table 1. Variable Hazard ratio (95% confidence interval) P-value Long pentraxin-3 ≥0.33 ng/mL 3.41 (1.27 - 9.11) 0.01 Age >65 years 0.38 (0.11 - 1.41) 0.15 Male gender 0.43 (0.13 - 1.44) 0.16 Diabetes Mellitus 1.24 (0.44 - 3.52) 0.68 Hypertension 0.64 (0.23 - 1.80) 0.39 Baseline creatinine ≥1.3 mg/dL 4.06 (1.43 - 11.53) 0.009 TIMI risk score > 4 8.31 (2.69 - 25.59) < 0.001 Multivariable Cox regression analysis showing association between PTX3 concentration and selected confounding variables for all-cause death at 30 day.
P18 The utility and validity of intracoronary administration of nicorandil alone for the measurement of fractional flow reserve in patients with intermediate coronary stenosis
Authors: Ishibuchi K , Fujii K , Tamaru H , Yamamoto W , Hasegawa K , Takiuchi S , Otsuji S , Higashino Y
Published: January 2020

Backgrand

Recently, intracoronary nicorandil (ICN) administration in addition to intravenous adenosine 5"-triphosphate (IVATP) is generally used to achieve maximal hyperemia for evaluating fractional flow reserve (FFR). This study investigated the usefulness and safety of ICN alone compared with  IVATP and ICN during IVATP for the achievement of maximal hyperemia in patients with suspected angina pectoris. 

Methods

Two-hundred-ten angiographically intermediate lesions in two-hundred-seven patients who underwent FFR assessments were enrolled. FFR was measured after ICN (2mg/5seconds), IVATP (150µg/kg/min) for 2 minutes, IVATP (210µg/km/min) for 2 minutes, and ICN (2mg/5seconds) during IVATP (150µg/kg/min). Maximal hyperemia was defined as the lowest FFR measured among each method.

Results

During the protocol, 92% of patients achieved maximal hyperemia with ICN2mg, 54% with IVATP 150µg/kg/min, 91% with IVATP 210µg/kg/min, and 99% with ICN2mg during IVATP 150µg/kg/min, respectively. The FFR obtained with ICN2mg were strongly correlated with those obtained with ICN2mg during IVATP150µg/kg/min (r²=0.93, P< 0.001). The mean aortic pressure drop during hyperemia was significantly lower in ICN2mg than in IVATP 150µg/kg/min, IVATP 210µg/kg/min, and ICN2mg during IVATP 150µg/kg/min(9 ± 10, 11 ± 14, 24 ± 17, and 27 ± 19mmHg, p < 0.001, respectively). Despite no side effects reported during hyperemia with ICN2mg alone, transient atrioventricular block was observed in 1(1%) patient with IVATP 150µg/kg/min and 9(4%) patients with IVATP 210µg/kg/min. Also, 20 (10%) patients with  IVATP 150µg/kg/min and 56(27%) with IVATP210µg/kg/min experienced chest discomfort during hyperemia.

Conclusions

The intracoronary administration of NIC2mg is safe and well tolerated, and shortens the procedure. Furthermore, intracoronary NIC2mg produced a more pronounced hyperemia than IVATP and may be the preferred mode of application for the assessment of FFR.
P37 Long-term outcomes of patients at risks for Fontan operation: role of temporary fenestration
Authors: Ozawa H , Hoashi T , Nakata T , Shimada M , Ichikawa H
Published: January 2020

Purpose

Whereas fenestration at Fontan operation was reported to be effective for smooth initiation to Fontan circulation, subsequently developed aortopulmonary collateral arteries under the presence of remaining hypoxia were a matter of concern.So as our institutional policy, it is closed as much and early as possible (temporary fenestration). This study aimed to reveal long-term outcomes for patients at riskswho underwent Fontan operation with temporary fenestration.

Methods

Of 107 patients undergoing Fontan operation from 1995 to 2004, 79 patients (73.8%) were free from any risks (NR group) and 28 patients (26.2%) had risks for Fontan operation (R group). Hypoplastic left heart syndrome, heterotaxy syndrome with obstructive total anomalous of pulmonary venous connection, and individual cases with high preoperative pulmonary artery pressure (PAP), systemic ventricular end diastolic pressure (SVEDP) or low ejection fraction (SVEF) were defined as a risk for Fontan completion.Age at Fontan operation was older in R group (6.6 vs 2.3years-old, p = 0.0004). Preoperative PAP (12.8 vs 11.3mmHg, p = 0.03) and SVEDP (8.8 vs 7.1mmHg, p = 0.02) were higher and SVEF (53.7 vs 60.0%, p = 0.002) was lower in R group. Pulmonary vascular resistance (PVR) was not different. Fenestration was created in all patients in R group, then it was closed at the mean duration of 2.9 years after Fontan operation.

Results

Freedom from death or protein-losing enteropathy rate at 5, 10, and 15 years after Fontan operation were 97, 96, and 93% in NR group and 96, 93, and 86% in R group (log-rank: p = 0.20). Fifty-one patients (64.6%) in NR group and 17 patients (60.7%) in R group underwent serial catheter examinations at 5, 10, and 15 years after Fontan operation and exercise capacity testing at 15 years after Fontan operation (Figure). In R group, arterial oxygen saturation was lower and PVR was higher even after close of fenestration (Figure). In addition, 12 patients (71%) in R group developed significant veno-venous collaterals, which were defined by more than 3mm in diameter of collateral veins or a condition where pulmonary veins were contrasted in venography. On the contrary, cardiac index (CI), SVEDP, and PAP were not different and no significant difference on peak oxygen uptake and anaerobic threshold were observed between in 2 groups. 

Conclusions

Although the mild cyanosis remained due to the development of veno-venous collaterals after the closure of temporary fenestration, CI, SVEDP and PAP well maintained in patients at risk for Fontan operation. These results might to lead acceptable life prognosis and freedom fromprotein-losing enteropathy rate for patients at risk for Fontan operation.

Abstract P37 Figure
P38 Developing a model for predicting in-hospital death in patients with the use of extracorporeal membrane oxygenation
Authors: Lin J W , Yu H Y , Chen Y S
Published: January 2020

Funding Acknowledgements

Minister of Science and Technology

Background

The objective of this study was to develop a predicting model for estimating the odds of in-hospital death in the patients who receive extracorporeal membrane oxygenation (ECMO).

Methods

Adult patients who received ECMO for a variety of etiologies in our National University Hospital from 2005 and 2016 were included. The demographic, anthropometric, hemodynamic, and laboratory data when ECMO was instituted were recorded for each individual. A logistic regression model was applied to find the risk variables that were independently associated with in-hospital mortality. The predicted probability derived from the model was used to plot a receiver-operating-characteristic (ROC) curve, and area under curve (AUC) was found to represent the differentiating capacity of this approach.

Results

A total of 919 patients (659 men and 260 women) were included in the analysis. The mean age was 53.7[SD 15.9] years. The analysis showed that age (odds ratio [OR]: 1.018, 95% confidence interval [CI]: 1.008-1.028 per year), blood urea nitrogen (1.008 [1.001-1.014] per mg/dL), use of inotropic agent in terms of inotropic equivalent (1.007 [1.002-1.013]), the presence of cardiogenic shock (1.910 [1.097-3.327]), and the need of hemodialysis (2.262 [1.304-3.926]) were positively associated with mortality. In addition, body surface area (OR: 0.414 [0.204-0.840] per square meter), systolic blood pressure (0.995 [0.990-0.999] per mmHg), Glasgow Coma Scale (0.928 [0.899-0.957] per unit), pH value (0.395 [0.158-0.988] for each unit), and urine output (OR: 0.974 [0.964-0.985] per dL) were negatively associated with the probability of in-hospital death. The AUC in ROC analysis was 0.754 (95% CI: 0.722-0.787).

Conclusion

The predicting model that used a simple set of physiological parameters could substantially discriminate whether the patients receiving ECMO could survive the in-hospital course. Further studies are needed to examine why false positive and false negative predictions took place.

Abstract P38 Figure.
P89 Role of inflammation as a risk factor for atrial fibrillation in rheumatic mitral stenosis and its correlation with atrial late gadolinium enhancement (LGE) on cardiac MRI
Authors: Malik M A , Sharma G , Ganga K P , Sharma S
Published: January 2020

Funding Acknowledgements

ICMR

Aims

Association of atrial fibrillation (AF) is a common cause of morbidity and mortality in patients with rheumatic heart disease (RHD). Association of Atrial Fibrillation with inflammation is well delineated in nonvalvular AF as compared to Rheumatic AF. This study evaluated the presence of atrial inflammation, in patients with AF and rheumatic mitral stenosis (MS), using cardiac MRI and its correlation with inflammatory markers.

Methods and Results

Twenty RHD patients with predominant mitral stenosis were recruited for the study. Ten patients had persistent AF, three had paroxysmal AF and seven were in sinus rhythm. Patients with AF had lower mitral valve areas. Cardiac MRI showed evidence of late gadolinium enhancement (LGE) in the atrial wall in 61.54% (8/13) of patients with AF as compared with only 20% (1/5; p < 0.05) of patients in sinus rhythm. Mean levels of IL-6 were also significantly higher in patients with AF (10.62 ± 5.92 pg/mL versus 4.37 ± 2.68 pg/mL; P= 0.017). IL6 with a cutoff of ≥ 6.5 pg/mL was associated with a sensitivity of 76.92 % and specificity of 71.43 % for prediction of AF. There was also significant association between high IL-6 levels and LGE on MRI (13.13 ± 5.75 pg/mL vs 5.29 ± 3.23pg/mL; P < 0.05)

Conclusion

Patients with MS who developed AF show evidence of atrial inflammatory sequelae in the form of fibrosis as suggested by LGE on cardiac MRI. Systemic inflammation in the form of elevated IL-6 levels correlated significantly with atrial fibrosis and AF.

Table 1: MS patients with or without AF Clinical Features Rhythm P-Value NSR (n = 7) AF (n = 13) Mean Valve Area (cm2) 1.28 ± 0.35 0.83 ± 0.26 < 0.01 Mean Diastolic Gradient (mmHg) 6.29 ± 2.2 11.92 ± 5.65 <0.01 Wilkin Score 7 ± 0.816 8.46 ± 1.66 0.04 LVEF % (non indexed) 59.57 ± 1.13 58.77 ± 2.89 0.49 LA Volume with MRI (ml) 127.50 ± 51.32 284.33 ± 133.12 <0.01 Inflammatory Markers hs-CRP (mg/L) 5.59 ± 3.89 3.94 ± 3.47 0.34 IL6 (pg/mL) 4.37 ± 2.68 10.62 ± 5.92 0.017 sCD-40L (ng/mL) 3.72 ± 3.73 4.77 ± 2.80 0.48 Atrial LGE 0 (0%) 8 (61.5%) 0.04

Abstract P89 Figure. Image 1: Cardiac MRI showing LGE
P103 Heart failure with preserved ejection fruction defines the progression of abnormal brain aging: a prospective study of young-old hypertensive patients
Authors: Nomoto K , Kawashima K , Hirashiki A , Kokubo M , Shimizu A , Arai H , Toba K , Murohara T
Published: January 2020

Funding Acknowledgements

Ministry of Health, Labor and Welfare (MHLW) Geriatrics and Gelontorogy sponsored research funds

Background & purpose: Recently, many longitudinal studies have shown that heart failure with reduced ejection fraction (HFrEF) is associated with various types of brain abnormalities: cerebral micro-bleeding, atrophy, or pathologic degeneration (white matter hyperintensity; WMH). These brain abnormalities are known to increase with aging and to be closely associated with cognitive impairment. Heart failure with preserved ejection fraction (HFpEF) also increases with aging, but there have been few longitudinal studies to address the relationship between HFpEF and brain abnormalities. Thus, this longitudinal study aimed to clarify this relationship by focusing on WMH volume.

METHODS

The participants were 111 well-controlled hypertensive patients aged between 65 and 75 years with normal LV contraction and no history of symptomatic heart failure, ischemic heart disease, atrial fibrillation, stroke, or cognitive dysfunction. The participants were classified into 3 groups: Low E/e", E/e" < 8; Middle E/e", 8≤ E/e" ≤ 15; and High E/e", E/e" > 15. WMH volume was quantified on brain magnetic resonance imaging using analytical software.

RESULTS

During the mean 2.6 ± 1.0-year follow-up period, the rate of increase of WMH volume was significantly higher in the high E/e" group (1.1 ± 1.2 mL/year) than in the low E/e" group (0.30 ± 0.78 mL/year; P = 0.0238). Linear regression analysis including other confounders showed that the only positive association was between the rate of increase of WMH volume and the E/e" ratio (beta- coefficient = 0.225, P = 0.018).

CONCLUSION

The severity of LV diastolic dysfunction is positively correlated with increasing WMH volume.

Abstract P103 Figure. The rates of increase of WMH volumes