bluuebunny/crossref_metadata_2025 huggingface dataset:
New Insight into the Comparative Power Quality-Control Rules That Use Control Observations within a Single Analytical Run
Authors: Parvin Curtis A
Published: January 2020

Vol. 39:

p. 441 In the article by C.A. Parvin Entitled "New Insight into the comparative power of quality-control rules that use control observations within a single analytical run," 1993;39;440-7, the means in the first line on page 441 should have been µ1 + σb1E1 and µ2 + σb2E1. In the third paragraph on page 441, in the Sentence "Finally, I assume that total analytical imprecision increases from its stable value, σtj, to REw = 1.5σtj, because of an increase in the between-run component of imprecision from its stable value, σwj, to an out-of-control value, σwj," the word "between" should have been "within."

pp. 565-572. In the review by M.H. zweig and G. Campbell entitled "Receiver operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine," 1993;39:561-77, the label for the x-axis at the bottom of each of Figures 4 through 12 should read "False-positive fraction (1 - specificity)." Correspondingly, the label at the top of each Figure should read "True-negative fraction (specificity)." Note that the (corect) dual labeling of the x-axis solves the problem of whether to plot specificity or 1 - specificity on the x-axis.

pp. 767-769. In the article by K. Emancipator and M.H. Kroll entitled "A quantitative measure of nonlinearity," 1993;39:766-772, three equations were printed incorrectly. They should have read as follows:

Equation 6a (p. 767)

Equation 8b (p. 768)

and on p. 769, the last unnumbered equation
Serum cholesterol determined by liquid chromatography with 6-chlorostigmasterol as internal standard
Authors: Chen W X , Li P Y , Wang S , Dong J , Li J Z
Published: January 2020

We describe an accurate and precise method for determining serum cholesterol by high-performance liquid chromatography (HPLC). After addition of 6-chlorostigmasterol as internal standard, serum is treated with alcoholic potassium hydroxide. Subsequently the cholesterol and internal standard are extracted from the mixture into n-hexane and then derivatized to phenylurethanes for measurement by HPLC with ultraviolet detection. The effective chromatographic separation and the use of an appropriate internal standard make this procedure free from interferences by other serum sterols and precise. The mean cholesterol concentration in Standard Reference Material (SRM) 909 (human serum) assayed by this procedure (4.346 mmol.g-1 x L-1) agreed well with the value assigned by the National Institute of Standards and Technology (4.359 mmol.g-1 x L-1). Within-run and total CVs were 0.56% and 0.78%, respectively. Therefore the performance of this procedure is sufficiently good to allow its use as a candidate reference method for serum cholesterol determination.
Calcium determination in serum with stable alkaline Arsenazo III and triglyceride clearing
Authors: Morgan B R , Artiss J D , Zak B
Published: January 2020

We describe an analytical procedure for determining serum calcium, using the ligand Arsenazo III in an aqueous alkaline medium. The choice of pH for the proposed technique differs from current procedures, which are for the most part carried out in a slightly acidic medium. An acidic medium avoids interference from magnesium, but is spectrophotometrically suboptimal for this pH-dependent reaction: the molar absorptivity of the Arsenazo III complex with calcium at acid pH is 13,787 L mol-1 cm-1, about one-half of that at a more optimal alkaline pH (26,574 L mol-1 cm-1). We have included a clearing technique in the reagent to avoid spectral aberrations from hypertriglyceridemic samples. alpha-Cyclodextrin absorbs the nonesterified fatty acids liberated from triglycerides by a microbial lipase. This modification may also be helpful for binding nonesterified fatty acids, which are known to interfere with calcium procedures by forming calcium soaps and thus preventing the reaction with intended ligands. The use of 8-hydroxyquinoline sulfonate as the magnesium-masking agent facilitates the use of alkaline pH. The less-water-soluble alternative, 8-hydroxyquinoline, commonly used as a precipitating agent for several methods, is difficult to solubilize in the alkaline reagent and tends to precipitate when complexed to magnesium. Finally, the use of alkaline pH results in a prolonged (> or = 6 weeks) shelf life for the reagent.
Time-resolved immunofluorometric assay of human growth hormone
Authors: Albertsson-Wikland K , Jansson C , Rosberg S , Novamo A
Published: January 2020

We describe a time-resolved immunofluorometric assay (trIFMA) for human growth hormone (hGH), in which monoclonal antibody (mAb)-coated microtiter strip wells and a europium (Eu) chelate-labeled mAb are used. We compare the new trIFMA, in which two mAbs are used, with an immunoradiometric assay (IRMA) in which polyclonal antibodies are used. Serum samples (n = 185) from 36 children with various diagnoses were analyzed. In addition, 24-h profile samples (72 per child) from 39 children were analyzed. The trIFMA was more sensitive (detection limit, 0.03 mIU/L) than existing IRMAs. Both the intra- and interassay CVs were < or = 10.6% for hGH concentrations between 1 and 100 mIU/L. The trIFMA is technically simple and rapid, requires no centrifugation or separation reagent, and has a counting time of only 1 s per sample. In addition, the Eu label is nontoxic, presents no waste-disposal problems, and has a long shelf-life. Finally, the assay requires only small volumes of serum (25 muL), which is of considerable importance in pediatric use. The mAbs used for the trIFMA selectively bind the 22-kDa form of hGH, with the result that the assay detects about 80% of the amount detected by the polyclonal IRMA.
Space-resolved fluoroimmunoassay for quantifying alpha-fetoprotein in serum
Authors: Wang W K , Ho L T , Chiang Y
Published: January 2020

A nickel-coated surface was used to adsorb a monolayer of anti-human alpha-fetoprotein antibody. After incubation with a patient's serum, the sample was stained with fluorescein isothiocyanate (FITC)-conjugated anti-human alpha-fetoprotein antibody. These slides were then read with a space-resolved fluorometer to determine the amount of FITC adsorbed onto the metal surface. We used an argon laser as the light source in the fluorometer. The parallel laser beam was tilted at about 45 degrees to the sample surface. The fluorescence from FITC was read with a perpendicular photon counter to reduce noise. The CV for these tests was approximately 10%. Comparison of these results (y) with those of a conventional radioimmunoassay (x) produced the regression equation y = 0.99x + 0.5, over the range 10-140 micrograms/L (n = 51).
Early diagnosis of acute myocardial infarction with use of a rapid immunochemical assay of creatine kinase MB isoenzyme
Authors: Collins D R , Wright D J , Rinsler M G , Thomas P , Bhattacharya S , Raftery E B
Published: January 2020

In 195 patients presenting with chest pain and referred acutely for cardiological assessment, blood was taken immediately for assay of creatine kinase (CK; EC 2.7.3.2) MB isoenzyme by an immunochemical method and results [mass units of enzyme per liter of plasma (microgram/L)] were obtained within 30 min of sampling. Diagnosis of acute myocardial infarction in the patients was made independently, based on electrocardiograms and conventional cardiac enzyme profiles. The administration of any thrombolytic therapy in response to the CK-MB concentration result was also noted, allowing assessment of the assay's potential influence on patient management in addition to the diagnostic efficiency evaluation. The study demonstrated that, when blood samples were collected on admission to hospital and the decision level suggested by the manufacturers was utilized, the assay had an immediate sensitivity of 52% and a specificity of 97%. Of the 81 patients who were shown by conventional means to have had acute myocardial infarction, 8 (10%) had equivocal electrocardiograms but positive CK-MB concentration results. In four of these patients (5%), thrombolytic therapy was given on the basis of the clinical features and a positive CK-MB concentration result alone.
Albuminuria in people at least 40 years old: effect of alcohol consumption, regular exercise, and cigarette smoking
Authors: Metcalf P A , Baker J R , Scragg R K , Dryson E , Scott A J , Wild C J
Published: January 2020

We investigated the relation between albuminuria and life-style factors in 5670 people, ages 40 years and over, who participated in a health screening survey of a local workforce. The degree of albuminuria showed piecewise log-linear relationships with alcohol consumption and cigarette smoking, with changes in slope (and 95% confidence interval) corresponding with 5 (2, 8) g of alcohol/day and 10 (6, 14) cigarettes/day. After adjusting for age, gender, ethnicity, and other life-style variables, relative risks (95% confidence interval) of slight albuminuria for people consuming > 32 g of alcohol/day compared with nondrinkers, and for cigarette smokers compared with nonsmokers, were 1.74 (1.02, 2.98) and 1.37 (1.01, 1.88), respectively. However, there was no significant effect of exercise. We conclude that slight albuminuria is significantly associated with cigarette smoking and heavy alcohol consumption, consistent with its role as an index of risk of cardiovascular disease.
Potential use of ketoconazole in a dynamic endocrine test to differentiate between biological outliers and testosterone use by athletes
Authors: Kicman A T , Oftebro H , Walker C , Norman N , Cowan D A
Published: January 2020

Determination of the ratio of testosterone to epitestosterone (T/E) in urine is used to detect testosterone administration in athletes, with a ratio > 6 considered as evidence of an offense. We show that administration of ketoconazole, which inhibits testosterone biosynthesis, may be useful for differentiating between an athlete who is using testosterone and one who naturally gives a ratio > 6. In a control subject pretreated with testosterone, ketoconazole caused the ratio to increase; conversely, it caused a decrease in the ratio in an athlete under investigation. Repeated administration of ketoconazole to two normal men caused a decrease in the ratio due to a large decrease in the urinary excretion rate of testosterone relative to epitestosterone. Stimulation with human chorionic gonadotropin exacerbated the differences in excretion rates. A single administration of ketoconazole to six normal men caused the T/E ratios to decrease significantly within 8 h, a suitable time scale for use in a dynamic test.
Intra- and interlaboratory quality control for assay of amino acids in biological fluids: 14 years of the French experience
Authors: Parvy P , Bardet J , Rabier D , Gasquet M , Kamoun P
Published: January 2020

The functioning of an external quality-control scheme for amino acids set up in 1978 is described. Two measurements were made each month by participating laboratories on a control plasma sample provided by the quality-control center; freeze-dried samples were used from 1978 to 1989 and liquid samples since 1990. In addition, two "blind" samples were sent to the laboratories each year. Every 3 months, the overall results and those of the individual laboratories were analyzed statistically. The validity of the liquid sample control is demonstrated. The progressive improvement of results is commendable. In 1990, the coefficients of variation for all participants ranged from 8.4% for alanine to 23.5% for methionine. The standards used for calibration could contribute to the broad range of results, especially those for histidine and ornithine. The use of blind samples made it possible to detect problems of calibration, of linearity of measurement, of contamination, and of identification of unusual amino acids.
Error-compensating kinetic method for enzymatic determination of DNAs
Authors: Lim K B , Pardue H L
Published: January 2020

We describe the adaptation and evaluation of an error-compensating method for kinetic determinations of deoxyribonucleic acids (DNAs). The DNA is first reacted with ethidium bromide to produce a fluorescent intercalation complex. Subsequent treatment of the complex with DNase catalyzes hydrolysis of the DNA, causing a time-dependent decrease in fluorescence, which is monitored. A model for two-component parallel first-order processes is fit to the decay curve to predict the total change in fluorescence expected if the process were monitored to equilibrium. The predicted change in fluorescence response varies linearly with DNA concentration with an intercept corresponding to 0.13 mg/L DNA. Results by the predictive method are 47-, 58-, and 250-fold less dependent on DNase activity, temperature, and ethidium bromide concentration, respectively, than are results for an initial-rate method utilizing the same data. Moreover, the predictive method yields a significantly wider linear range than the initial-rate method, and is much less affected by blank fluorescence and RNA interference than is an equilibrium method based on the reaction of DNA with ethidium bromide alone.
Revised structure of a delta-aminolevulinic acid derivative
Authors: Kajiwara M , Hara K , Takatori K , Matsumoto K
Published: January 2020

The structure of the fluorescent derivative formed in the method of Okayama et al. (Clin Chem 1990; 36:1494-7) for determining delta-aminolevulinic acid (ALA) concentrations was reinvestigated after esterification. The molecular ion peak at m/z 303.1473 corresponded to the molecular formula of C17H21NO4 (calcd 303.1470). The infrared spectrum showed the presence of carbonyl and carboxyl groups. This compound contained two acetyl groups, two methyl groups, and one methoxycarbonylethyl group, as revealed by 1H and 13C nuclear magnetic resonance and 13C-1H shift-correlated spectroscopy. Experiments with correlation spectroscopy via long-range coupling indicated that the main skeleton is 3H-pyrrolizine. The relative arrangement of functional groups was determined by means of nuclear Overhauser effect difference experiments. We were led to the conclusion that the methyl ester of the derivative is 2,6-diacetyl-1,5-dimethyl-7-(2-methoxycarbonylethyl)-3H-pyrrolizine. This structure was unequivocally confirmed by x-ray analysis; therefore, the structure of the derivative itself is 2,6-diacetyl-1,5-dimethyl-7-(2-carboxyethyl)-3H-pyrrolizine.
Multianalyte assay system developed for drugs of abuse
Authors: Parsons R G , Kowal R , LeBlond D , Yue V T , Neargarder L , Bond L , Garcia D , Slater D , Rogers P
Published: January 2020

A simple, 10-min immunoassay system has been developed that simultaneously screens for five different classes of drugs of abuse in a urine sample. This system tests for amphetamines, cannabinoids, cocaine metabolites, opiates, and phencyclidine, and each assay has a specific preset cutoff concentration. Accuracy is > 99% for reporting positive or negative results for samples with 200% or 50%, respectively, of the cutoff concentrations of the drugs. Tests of a panel of 96 compounds yielded only three cases of nonspecific reactivity (at a drug concentration of 100 mg/L). Another panel of 12 compounds that could normally be found in urine samples was also evaluated and no interferences were observed. Concordance was > 95% between this system and the comparable automated immunoassays for detecting drugs of abuse. Greater than 98% of GC/MS-confirmed positive samples gave positive results with this assay system.
Diagnosis of peroxisomal disorders by analysis of phytanic and pristanic acids in stored blood spots collected at neonatal screening
Authors: ten Brink H J , van den Heuvel C M , Christensen E , Largillière C , Jakobs C
Published: January 2020

Concentrations of phytanic acid and pristanic acid were measured in stored dried blood spots collected at neonatal screening from patients with peroxisomal disorders, and compared with concentrations in control blood spots. In blood spots from two patients with Zellweger syndrome both phytanic acid and pristanic acid concentrations were increased but their concentration ratio was normal. In the blood spot from a patient with rhizomelic chondrodysplasia punctata, the concentration of phytanic acid was increased, whereas pristanic acid was within the control range, resulting in a low pristanic acid/phytanic acid ratio. In the blood spot from a patient with X-linked adrenoleukodystrophy, the concentrations of the acids and their ratio were normal. These findings are consistent with results for these acids in plasma from such patients. Measurement of phytanic acid and pristanic acid and their ratios in stored dried blood collected at neonatal screening can therefore be used in the diagnosis of peroxisomal disorders, especially for those cases in which, owing to early death of the patient, no other material is available for biochemical investigations.
Solid-phase extraction technique for gas-chromatographic profiling of acylcarnitines
Authors: Van Bocxlaer J F , De Leenheer A P
Published: January 2020

We present a simple, new clean-up method for the gas-chromatographic profiling analysis of acylcarnitines. The use of a solid-phase, cation-exchange extraction combined with gas-chromatographic separation, based on the derivatization into acyloxylactones by Lowes and Rose (Analyst 1990;115:511-6), allows a selective and sensitive screening for acylcarnitines in urine. As such, a quantitative approach was developed for differential evaluation of acylcarnitines for detection of inborn errors of metabolism; the evaluation is both fast and routinely applicable in any biochemical laboratory. We validate the analysis method for acylcarnitines of various chain-lengths and present examples of its application to urine samples from diseased patients. We give special attention to the medium-chain acylcarnitines because of their association with medium-chain acylCoA dehydrogenase deficiency. Finally, the quantitative nature of the analysis allows evaluation of the acylcarnitine excretion over time.
A transcriptionally amplified DNA probe assay with ligatable probes and immunochemical detection
Authors: Carpenter W R , Schutzbank T E , Tevere V J , Tocyloski K R , Dattagupta N , Yeung K K
Published: January 2020

Transcriptionally amplified DNA probes are valuable tools in the development of sensitive nucleic acid-based diagnostic assays. Here we describe a model assay using a novel oligonucleotide hairpin probe that encodes a T7 RNA polymerase promoter. The hairpin probe and an adjacently hybridizing biotinylated capture probe were hybridized to target DNA and the duplex was captured onto streptavidin-coated magnetic particles. After ligation of the immobilized probes, which served to maintain specificity, the hairpin probe was transcribed by T7 RNA polymerase. The amplified RNA product was hybridized to the capture probe and bound to the streptavidin-coated magnetic particles. The immobilized heteroduplex was detected with an antibody-alkaline phosphatase conjugate specific for DNA:RNA hybrids, and the chemiluminescent substrate adamantyl-1,2-dioxetane phenyl phosphate. Ten attomoles of target DNA could be detected in a background of 5 micrograms of unrelated DNA. The chemiluminescent immunoassay was as sensitive as radioactive detection of specific product after gel electrophoresis.
Homogeneous detection of nucleic acids by transient-state polarized fluorescence
Authors: Devlin R , Studholme R M , Dandliker W B , Fahy E , Blumeyer K , Ghosh S S
Published: January 2020

We describe a transient-state polarized fluorescence-based method for detecting nucleic acids. An active ester of the phthalocyanine dye La Jolla Blue was coupled to an oligonucleotide containing an amino group at its 5' end, and the conjugate was purified by HPLC chromatography. We monitored the hybridization characteristics of the conjugate with complementary oligonucleotides and RNA as targets by transient-state polarized fluorescence measurements. The method was comparable in sensitivity to isotopic and nonisotopic heterogeneous detection systems and was capable of detecting 1 fmol of a 382-base-long RNA transcript from human immunodeficiency virus type (HIV-1) generated in a self-sustained sequence replication (3SR) reaction.
Molecular engineering: applications to the clinical laboratory
Authors: Hamilton R G
Published: January 2020

Advances in cellular and molecular biology methods have led to the molecular engineering of novel human biomolecules, some of which have been successfully applied to the documentation of clinical laboratory assays. Here I describe the use of engineered chimeric antibodies in the clinical immunology laboratory in three principal applications: (a) as reference proteins to document the specificity of clinical assay reagents, be used as reagent-grade purified antigens, and facilitate the epitope mapping of antibody reagents; (b) as calibration proteins to assign mass/volume estimates to proposed antibody standards; and (c) as interference proteins to study the effects of naturally occurring autoantibodies on the accuracy and sensitivity of current clinical assays. The model recombinant proteins used for these illustrations are chimeric antibodies with a defined V-region specificity for one of two haptens (nitrophenyl or dansyl) and C-region domains covering a spectrum of human isotypes. I also describe a panel of mutant human IgG1-4 anti-dansyl chimeric antibodies that have been genetically engineered with swapped, deleted, or point-mutated wild-type C-region exons and used as specialized reagents for mapping the epitopes to which clinically used human IgG-specific monoclonal antibodies bind. Finally, the use of a recombinant human IgG1 anti-human IgE Fc chimeric antibody to simulate human IgG anti-IgE autoantibody interference in assays of total serum IgE is investigated.
65 Clinical depression among post- acute coronary syndrome patients: A prospective single tertiary centre analysis
Authors: Leong L , Mahmood Zuhdi A S , Abdul Hafidz M I
Published: January 2020

Background

Clinical depression is a known consequence of acute coronary syndrome (ACS). It is also known to carry an adverse outcome among these patients. Despite the availability of validated tools for screening of depression in acute coronary syndrome patients, depression is still significantly under-recognized and undertreated in patients with acute coronary syndrome.

Purpose

To investigate the prevalence of depression in post-ACS patients and the factors associated with it.

Methods

Prospective cohort study conducted on 95 ACS patients (26 female, 69 male) admitted to our cardiology ward University. Data collected with consent from patients through electronic medical record and Patient Health Questionnaire (PHQ-9), Medical Adherence Questionnaire(MAQ). Depression outcome at 30-day was obtained from hospital records and via phone call to the patient. Data analyzed using SPSS 24.0. Chi-square test was used for comparison of categorical variables and independent t-test and Mann-Whitney U tests were used for comparison of continuous variables. Binary logistic regression was used to determine the independent associated factors for depression after adjusted with significant demographic variables and clinical characteristics. The strength of this association was presented in odds ratio (OR) and 95% confidence interval (CI). The significance level adopted was 0.05.

Results

Mean age of the study population is 60 years old. 72.6% were male and 27.4% female. Symptoms of depression (mild to severe) were present in 88.4% of patients at baseline. Among the depressed patients, 22.6% of the cases were found to have for severe depression, 14.3% moderately-severe depressed, 15.5% moderately depressed, 27.4% for mildly depressed and 20.2% for minimally depressed. Depression at 30-day post discharge is more likely in women, diabetics and dialysis patients (p= 0.024, p < 0.001, p= 0.008 respectively). There was no difference in depression among ethnicity. Patients with baseline moderate to severe depression are more likely to have moderate to severe depression at 30 days (p < 0.001). Patients with low adherence to medications at 30 days reported moderate to severe depression at 30 days (p = 0.007). Baseline depression is the strongest predictor of 30-days depression. An increase in one unit of PHQ-9 baseline score increases the risk of developing severe depression after 30 days by 29%. There is no difference in terms of mortality between patients with significant depression and those without.

Conclusions

Clinical depression is prevalent in our post-ACS patients. Associated factors are female gender, diabetics and dialysis patients. Depression at baseline predicts clinical depression at 30-days post discharge and is associated with low adherence to their medications. Thus we should actively screen for depression among ACS patients in order to administer appropriate treatment.
148 Inappropriate elevation of angiopoietin-2 relative to hemodynamic stability is associated with bleeding events in patients with continuous flow mechanical circulatory support
Authors: Nakamura M , Hori M , Nakagaito M , Kinugawa K
Published: January 2020

Funding Acknowledgements

none

Background

Elevated angiopoietin-2 (Ang-2) has been attributable to a potential cause of gastrointestinal bleeding among patients with continuous flow (CF) mechanical circulatory support (MCS) in the US, but Ang-2 levels have not been examined in the Japanese MCS patients who are likely to have less gastrointestinal bleeding.

Methods

We enrolled 18 patients (64 ± 16y; LVEF 26 ± 9%) with advanced heart failure (HF) who received temporary or durable MCS, or were given intravenous inotropes from August 2018 to January 2019. Serum Ang-2 and plasma BNP were simultaneously measured at various treatment status. The relationship between each value and any spontaneous bleeding events requiring hemostasis or blood transfusion was examined.

Results

103 blood samples were collected and divided into 2 groups. One was the CF group, which consisted of samples from patients under CF-MCS (Impella, ECMO, Jarvik2000, HeartMateII), and the others were assigned to the Non-CF group. Ang-2 levels had a positive correlation with BNP levels (r = 0.33, p = 0.0006, Fig). CF-MCS efficiently lowered BNP levels (353 ± 125 in CF vs 1053 ± 119 in Non-CF, pg/mL, p < 0.0001), but Ang-2 levels relative to BNP levels were significantly higher in the CF group as shown in the Figure (Ang-2/log10(BNP) ratio: 3.77 ± 0.30 in CF vs 2.43 ± 0.29 in Non-CF, p = 0.0017). Bleeding events were remarkably frequent when Ang-2/log10(BNP)>3.17 (77.8%) than ≦3.17 (22.2%, p = 0.0002).

Conclusions

High Ang-2 level is normally a marker for hemodynamic compromise, but CF-MCS may stimulate Ang-2 production despite hemodynamic stabilization. Most of spontaneous bleeding events accompany inappropriately high Ang-2 relative to BNP level among Japanese patients with advanced HF.

Abstract 148 Figure. Correlation between Ang-2 and BNP
299 The prevalence and role of SCN10A variants in Han Chinese patients with Brugada syndrome: the SADS-TW BrS registry
Authors: Chen C-Y , Liu Y-B , Lu T-P , Yu Q-Y , Lin L-Y , Yu C-C , Makita N , Ishikawa T , Lai L-P , Hwang J-J , Yeh S-F , Lin J-L , Juang J-M , Horie M , Antzelevitch C
Published: January 2020

On Behalf

SADS-TW BrS registry

Background

Brugada syndrome (BrS) is an inheritable arrhythmic disease responsible for sudden cardiac death. Information on the prevalence and role of SCN10A variants in BrS is limited and equivocal.

Purpose

We aimed to investigate the prevalence and role of SCN10A variants in BrS in Han Chinese.

Methods

From 2000 to 2017, we prospectively and consecutively enrolled 176 unrelated BrS patients from the Han Chinese population in Taiwan (the SADS-TW BrS registry). Thirty-four BrS-related genes were screened by next-generation sequencing, using Taiwan Biobank as the population reference. The pathogenicity was evaluated by literature review and in silico analyses, including the SKAT-O algorithm.

Results

The SKAT-O algorithm showed that rare variants of SCN10A, but not common variants, were significantly different between BrS patients and healthy controls in the additive and dominant models (p-value <0.001), suggesting that rare SCN10A variants may play a role in BrS. Six likely pathogenic SCN10A variants were found in 6 patients and were compared to 25 pathogenic or likely pathogenic SCN5A variants found in 29 patients. The patients with likely pathogenic SCN10A variants tended to exhibit sudden death in older age and have a shorter QRS interval than those carrying pathogenic or likely pathogenic SCN5A variants or no variants in either gene (p = 0.06, 0.07, respectively). Collectively, the prevalence of likely pathogenic SCN10A variants was 3.4% in Han Chinese patients with BrS in Taiwan.

Conclusions

SCN10A likely pathogenic variants were present in 3.4% of Han Chinese BrS patients. Rare SCN10A variants may play a role in BrS, and may have impact on clinical and electrocardiographic manifestations.

Table 1. Patient Nucleotide Amino acid TWB gnomAD_EA REVEL CADD PHRED SIFT Polyphen-2 GERP++ 1 c.5789A > T p.D1930V 0.001318 0.0008700 0.479 24.5 Damaging Possibly damaging 4.22 2 c.2341G > A p.G781R 0 0.00005301 0.866 33 Damaging Probably damaging 4.83 3 c.5587C > T p.R1863W 0.000502 0 0.832 27.8 Damaging Probably damaging 1.97 4 c.2161C > T p.P721S 0.000989 0.0009016 0.933 28.5 Damaging Probably damaging 4.19 5 c.3749G > A p.R1250Q 0 0 0.907 31 Damaging Probably damaging 4.23 6 c.1825A > T p.R609W 0.000659 0.0001591 0.811 32 Damaging Probably damaging 4.28 Clinical and predicted functional characteristics of 6 likely pathogenic SCN10A variants. EA = East Asian; GERP = Genomic Evolutionary Rate Profiling; TWB = Taiwan Biobank. Transcript: NM_006514.3.

Abstract 299 Figure. Location of the SCN10A variants
P7 The impact of coronary calcification on diagnostic performance of workstation CT derived fractional flow reserve - a multicentre experience
Authors: Ihdayhid A R , Motoyama S , Fujimoto S , Isa M , Nerlekar N , Kato E , Miyajima K , Comella A , Kamo Y , Sarai M , Kawai H , Arakita K , Hislop-Jambrich J , Cameron J , Ko B
Published: January 2020

Background

On-site workstation based computed tomography derived fractional flow reserve (CT-FFR) is an emerging method to assess the vessel specific ischaemia in coronary artery disease (CAD). The impact of coronary calcification on its diagnostic performance is unknown.

Purpose

To evaluate the impact of coronary calcification on the diagnostic performance of reduced-order CT-FFR at detecting vessel specific ischaemia.

Methods

This is a retrospective pooled analysis of 141 patients with suspected CAD enrolled from 3 global centres who underwent CT-coronary angiography (CTA), onsite CT-FFR and invasive FFR.  Coronary calcification was assessed by Agatston score (AS). The diagnostic performance of CT-FFR (≤0.8) and CTA (≥50%) in evaluation of vessel specific ischaemia (FFR ≤ 0.8) was assessed across AS quartiles (Q1-4). A comparison of diagnostic performance of the low to mid AS (Q1 to Q3) versus high AS (Q4) was performed.

Results

Mean age and median AS was 65.8 ± 9.9 and 327.3 (interquartile range = 78.5 – 798.1). Diagnostic accuracy, sensitivity and specificity of CT-FFR for low-mid AS (0-798) and high AS (799-4019) were 77.4% vs 82.9%; 78.9% vs 94.7%; 68.8% vs 76.5% respectively with no statistical difference between the two groups.  The AUC for ischaemia of CT-FFR in low to mid AS was comparable with AUC in the high AS (0.76 [95% CI: 0.66-0.86] vs 0.84 [0.69-0.99]; P = 0.397).  The AUC for ischemia for CT-FFR in both low to mid AS and high AS was significantly higher than for CTA (0.76 [0.66-0.86] vs 0.57 [0.50-0.64]; P = 0.003 and 0.84 [0.69-0.99] vs 0.48 [0.38-0.57]; P < 0.001 respectively).

Conclusion

On-site workstation CT-FFR demonstrated consistently high diagnostic performance in patients with high AS. Its diagnostic performance was superior when compared with significant stenosis assessment on CTA across all spectrum of Agatston scores.
P9 Novel use of CHA2DS2VASC score to select patients to undergo repeat atrial fibrillation screening
Authors: Sun W , Yan B P Y
Published: January 2020

Background

We have previously demonstrated unselected screening for atrial fibrillation (AF) in patients ≥65 years old in an out-patient setting yielded 1-2% new AF each time screen-negative patients underwent repeated screening at 12 to 18 month interval. Selection criteria to identify high-risk patients for repeated AF screening may be more efficient than repeat screening on all patients.

Aims

This study aimed to validate CHA2DS2VASC score as a predictive model to select target population for repeat AF screening.

Methods

17,745 consecutive patients underwent 24,363 index AF screening (26.9% patients underwent repeated screening) using a handheld single-lead ECG (AliveCor) from Dec 2014 to Dec 2017 (NCT02409654). Adverse clinical outcomes to be predicted included (i) new AF detection by repeated screening; (ii) new AF clinically diagnosed during follow-up and (ii) ischemic stroke/transient ischemic attack (TIA) during follow-up. Performance evaluation and validation of CHA2DS2VASC score as a prediction model was based on 15,732 subjects, 35,643 person-years of follow-up and 765 outcomes. Internal validation was conducted by method of k-fold cross-validation (k = n = 15,732, i.e., Leave-One-Out cross-validation). Performance measures included c-index for discriminatory ability and decision curve analysis for clinical utility. Risk groups were defined as ≤1, 2-3, or ≥4 for CHA2DS2VASC scores. Calibration was assessed by comparing proportions of actual observed events.

Results

CHA2DS2VASC scores achieved acceptable discrimination with c-index of 0.762 (95%CI: 0.746-0.777) for derivation and 0.703 for cross-validation. Decision curve analysis showed the use of CHA2DS2VASC to select patients for rescreening was superior to rescreening all or no patients in terms of net benefit across all reasonable threshold probability (Figure 1, left). Predicted and observed probabilities of adverse clinical outcomes progressively increased with increasing CHA2DS2VASC score (Figure 1, right): 0.7% outcome events in low-risk group (CHA2DS2VASC ≤1, predicted prob. ≤0.86%), 3.5% intermediate-risk group (CHA2DS2VASC 2-3, predicted prob. 2.62%-4.43%) and 11.3% in high-risk group (CHA2DS2VASC ≥4, predicted prob. ≥8.50%). The odds ratio for outcome events were 4.88 (95%CI: 3.43-6.96) for intermediate-versus-low risk group, and 17.37 (95%CI: 12.36-24.42) for high-versus-low risk group. 

Conclusion

Repeat AF screening on high-risk population may be more efficient than rescreening all screen-negative individuals. CHA2DS2VASC scores may be used as a selection tool to identify high-risk patients to undergo repeat AF screening.

Abstract P9 Figure 1
P15 Serum chloride as marker for prognosis for patient with acute decompensated heart failure: a systematic review and meta-analysis on prognosis
Authors: Evangelista L K , Ramos J D , Villanueva D L , Tiongson M D , Punzalan F E
Published: January 2020

Background

 Several studies have suggested that hypochloremia is associated with adverse outcomes among patients with heart failure. The association appears to be more marked in those with acute decompensation.

Research Question: What is the association of hypochloremia with mortality and worsening heart failure among patients in acute decompensation?

Objective

Determine the association of admission hypochloremia to all-cause mortality, heart failure death and worsening heart failure among patients with acute decompensated heart failure.

Criteria for Inclusion of Studies: Studies were included if they satisfied the following criteria 1) observational cohort studies; 2) included patients admitted for acute decompensated heart failure; and 3) reported data on mortality and worsening heart failure in association with admission hypochloremia.

Methods

A systematic search using MEDLINE, Clinical Key, ScienceDirect, Scopus, and Cochrane Central Register of Controlled Trials databases was done, from June 2018 to January 31, 2019. The characteristics of included studies were collated. Data abstraction and quality assessment, using the Newcastle-Ottawa Quality Assessment Scale, were done independently by two reviewers, and disagreements were settled by a third reviewer. Review Manager (RevMan) 5.3 was utilized to perform Mantel-Haenzel analysis of random effects and compute for relative risk.

Results

We included three high quality cohort studies involving 3,444 patients admitted for acute decompensated heart failure and having low serum chloride levels on admission. Our study shows that admission hypochloremia is associated with increased risk for all-cause mortality [RR 1.63, (95% CI 1.60 to 2.28, p < 0.00001]. Risks for heart failure death as mentioned in one study and worsening heart failure also in one study are likewise increased with hypochloremia on admission. 

Conclusion

Admission hypochloremia is associated with higher all-cause mortality among patients admitted for acute decompensated heart failure. The risk for heart failure death and worsening heart failure are also increased. Admission hypochloremia may be a useful prognosticator for heart failure patients.
P17 In-hospital mortality and clinical features of Japanese patients with acute myocardial infarction diagnosed by universal definition in real world from kanagawa-acute cardiovascular registry (K-ACTIVE)
Authors: Sone H , Mori H , Maeda A , Akashi Y , Ako J , Ikari Y , Ebina T , Sato N , Tamura K , Namiki A , Fukui K , Michishita I , Kimura K , Suzuki H
Published: January 2020

Background

Cardiac troponin (cTn) has been used as the preferred biomarker of myocardial injury for diagnosis of acute myocardial infraction (AMI) by universal definition. A large number of patients formerly classified by creatine kinase (CK) as unstable angina with the WHO criteria in Japan are now diagnosed by cTn as non-ST elevation myocardial infarction (NSTEMI). In this report, we aimed to understand its prevalence and clinical features of AMI diagnosed by using universal definition and the WHO criterial in real world. 

Method

This registry is a cross-sectional study of 53 facilities in Kanagawa prefecture of Japan. 4372 AMI patients were enrolled who received primary percutaneous coronary intervention (PCI) between October 1, 2015 and January 29, 2019. Patients were divided into 3 groups, 3268 patients with ST elevation myocardial infarction (STEMI), 628 patients with NSTEMI patients who satisfied the WHO criteria with CK elevation beyond twice upper limit of normal (NSTEMI + CK), and 476 patients with NSTEMI who didn’t satisfy the WHO criteria without CK elevation (NSTEMI-CK).

Result

Baseline clinical characteristics of the study patients are shown in Table 1. In-hospital mortality was significantly lower in patients with NSTEMI-CK (1.9%) than in STEMI (6.0%, P < 0.001) and NSTEMI + CK (5.3%, P < 0.004) (Figure 1). Kaplan-Meier analyses for 0-30 days of cardiac death are shown in Figure 2. From day 0, the Kaplan-Meier curves began to diverge in favor of NSTEMI-CK for up to 30 days.

Conclusion

AMI patients showed distinct clinical features depends on the type. We should be aware of the difference for the diagnosis of AMI by using universal definitions.

Table 1. 　 STEMI (n = 3268) NSTEMI + CK (n = 628) NSTEMI-CK (n = 476) STEMI vs NSTEMI + CK P value STEMI vs NSTEMI-CK P value NSTEMI + CK vs NSTEMI-CK P value Age(years) 68(59-77) 69(61-78) 70(61-79) 　 　 　 Male 76% 77% 75% 0.54 0.74 0.47 Concomitant diseases 　 　 　 　 　 　 Hypertention 65.4% 70.5% 69.3% 0.013 0.097 0.65 Diabetes 33.5% 36.5% 37.3% 0.15 0.11 0.78 Dyslipidemia 56.1% 61.2% 61.3% 0.018 0.03 0.96 Hemodialysis 2.3% 2.1% 6.8% 0.86 <0.001 0.01 Smoking 66.3% 63.1% 64.6% 0.13 0.48 0.62 Atrial fibrillation 9.6% 10.7% 14.4% 0.57 0.04 0.23 Previous MI 8.3% 17.3% 15.7% <0.001 <0.001 0.47 In-hospital mortality 6.0% 5.3% 1.9% 0.49 <0.001 0.004

Abstract P17 Figure 1. 2.
P22 Complete versus culprit only revascularization in STEMI: a single centre experience
Authors: So T
Published: January 2020

Introduction

Multiple vessel disease in STEMI is not uncommon, approximately half of STEMI patient presented with multiple vessel disease. In STEMI with multiple vessel disease that is not in cardiogenic shock, it is unclear whether complete or culprit only revascularization achieve better clinical outcome. Several trials, such as PRAMI, The CvLPRIT study, DANAMI-3 PRIMULTI, have shown mortality benefit favoring complete revascularization. Yet in a lack of large scale randomized control trial, there is no strong evidence.

Purpose

To evaluate whether complete or culprit only revascularization in STEMI with multi-vessel disease (non-cardiogenic shock) achieve better clinical outcome

Method

A retrospective review of patient with STEMI and multiple vessel disease (defined as angiographic stenosis 70% and more than single vessel involvment) that is not cardiogenic shock. Data was collected in a local hospital in the period of 1/2013 to 12/2017. The end-point

follow-up was up to 12 months. Primary outcome was major adverse cardiac event (MACE), comprising all-cause mortality, recurrent myocardial infraction, heart failure, ventricular arrhythmia. The outcome variable was analyzed by time-to-first event survival analysis, Cox proportional hazard models was used to estimate hazard ratios and 95% confidence interval. Data was analyzed by software SPSS.

Result

A total number of 112 patients were included in the study. There are 69 patient in culprit group while 43 patient in complete group. In culprit only group, 17 out of 69 patients developed MACE

(24.6%) while in complete revascularization group, 11 out of 43 patients had MACE (25.6%) (Hazard ratio: 0.942; 95% confidence interval 0.441 to 2.011; p = 0.877).

Conclusion

There is no significant difference in MACE in complete revascularization and culprit only group in STEMI patient and multiple vessel disease (non-cardiogenic shock). Our result differs from previous trials, possibly due to sample size and study design. In view of heterogeneity of study design in different trials and absence of solid clinical evidence, further study is needed to determine the optimal strategy for revascularization in patient with STEMI and multiple vessel disease (non-cardiogenic shock).
P25 Polymorphism of CYP2C19 is associated with poor platelet response to clopidogrel and indirectly affect TIMIi-flow among asian patients with STEMI undergoing primary PCI
Authors: Kemalasari A , Sukmawan R , Adiarto S
Published: January 2020

Background

The platelet response to clopidogrel treatment is very important in patients with myocardial infarction undergoing primary PCI.  Asian populations have been shown to have higher proportion of CYP2C19 gene polymorphism that may alter biotransformation of clopidogrel, than Caucasians. However, It is unclear whether platelet reactivity measured by P2Y12 reaction unit (PRU) is affected by CYP2C19 polymorphism, and whether it will impair coronary flow among Asian patients with STEMI after primary PCI.  Purpose: We sought to define whether polymorphisms on CYP2C19 genes will affect platelet reactivity response to Clopidgrel therapy, and whether subsequently it will affect the TIMI flow in Asian patients with STEMI undergoing primary PCI. Method: We studied 90 patients with STEMI receiving 600 mg loading dose of clopidogrel prior to primary PCI. High-on-treatment platelet reactivity was evaluated using the VerifyNow Assay. Patients with platelet reactivity more than 208 PRU are categorized as non-responders to Clopidogrel. Genotyping of CYP2C19 was performed by real-time polymerase chain reaction (PCR). Post primary PCI TIMI flow was categorized into good (TIMI flow 3), and impaired (TIMI flow <3). Results: Among all 90 patients (median age = 54.5 years old; 93.3% male), there were 36.6 % patients with CYP2C19 polymorhisms, carrying *2 or *3 alleles. Platelet reactivity test revealed 23.4% of all patients were Clopidogrel non-responders. Multivariate analysis showed CYP2C19 polymorphism is associated with Clopidogrel non-reponders (OR 4.7, p = 0.030), along with other factors such as: Diabetes, Renal impairment, and use of proton pump inhibitor drugs. After successful stent implantation during primary PCI,  there were  24.4% patients still with TIMI flow < 3. There was no direct correlation between CYP2C19 polymorphism and TIMI flow < 3 after primary PCI. However, we found significant association between Clopidogrel non-reponders and TMI flow < 3 after primary PCI in those STEMI patients (OR 3.3, p = 0.046). Conclusions: In Asian patients with STEMI receiving clopidogrel prior to primary PCI, the CYP2C19 polymorphisms is associated with poor platelet response to Clopidogrel therapy. The Clopidogrel non-responders is associated with impaired TIMI flow after primary PCI.
P29 Arrest of progression of cardiac amyloidosis after chemotherapy predicts favorable outcome in patients with light-chain amyloidosis
Authors: Koyama J , Minamisawa M , Kuwahara K
Published: January 2020

Funding Acknowledgements

none

Background

Many studies demonstrated that cardiac involvement predicts poor prognosis in patients with systemic light-chain amyloidosis (AL). There is no data about the effect of the arrest of progression of cardiac amyloidosis on prognosis after chemotherapy.

Hypothesis

Arrest of progression of cardiac amyloidosis is associated with favorable outcome in patients with light-chain amyloidosis.

Methods

Among 126 consecutive patients with AL, we prospectively examined 94 patients serially after optimal therapy. The mean follow-up period was 1405 ± 1510 days (median value 734 days, inter quartile range 176-2343 days). Wall thickness was measured from left ventricular (LV) m-mode trace. We defined the cardiac involvement as mean LV wall thickness >12mm, and the regression or progression of cardiac amyloidosis as change in LV mean wall thickness >1mm.

Results

Among 94 patients with AL, 28 patients (30%) showed regression by definition above, 35 patients (37%) showed no interval change and 31 patients (33%) showed progression of cardiac amyloidosis. Survival analysis of 3 groups demonstrated that the regression and arrest of progression groups showed better outcome compared with the progression group (Log-rank test P < 0.0001).

Conclusions

The arrest of progression of cardiac amyloidosis predicts favorable outcome in patients with AL amyloidosis.

Abstract P29 Figure. Kaplan-Meier Curve of 3 groups