bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of sensitive immunoassays to detect amylin and amylin-like peptides in unextracted plasma
Authors: Percy A J , Trainor D A , Rittenhouse J , Phelps J , Koda J E
Published: January 2020

Amylin is a 37-amino-acid polypeptide synthesized in and secreted from pancreatic beta cells along with insulin. Its biological actions include the slowing and reduction of postmeal increases in plasma glucose concentrations. Studies of the basic amylin biology in humans have been hampered by the lack of a rapid, sensitive assay capable of measuring physiological concentrations of amylin in small volumes of plasma. We report here two sandwich-type immunoassays that use pairs of monoclonal antibodies, the fluorescent substrate 4-methylumbelliferyl phosphate, and the enzyme alkaline phosphatase. The minimum detectable concentration of amylin in 50 microL of plasma was 0.5 to 2 pmol/L, and the dynamic range was 2 to 100 pmol/L. The assays had average intraassay CVs of <10%, average interassay CVs of <15%, and good linearity on dilution and recovery of added amylin. The two assays use the same detection antibody, which binds to the carboxyl terminus of the molecule, but different capture antibodies. One of the assays measures only human amylin; the other also detects amylin-like peptides. Examples of measurements in human plasma are provided in subjects with impaired glucose tolerance and in nondiabetic controls.
Use of neural networks to diagnose acute myocardial infarction. II. A clinical application
Authors: Pedersen S M , Jørgensen J S , Pedersen J B
Published: January 2020

We investigated the ability of neural networks to diagnose acute myocardial infarction (AMI) from laboratory data only. Several networks were trained with different combinations of data obtained at admission and within the first 12 h and 24 h after admission. The data used included the electrocardiogram (ECG) and the concentrations in serum of potassium, creatine kinase B-subunit (CKB), and lactate dehydrogenase isoenzyme 1 for 250 patients with suspected AMI. Based on admission data, the correct diagnosis was predicted for 76% of the patients in the test group from the ECG data only, and the best combination of ECG results with other variables yielded correct diagnoses for 85% of the test group. Using all of the data available within 24 h, the network predicted the correct diagnosis for 99% of the test data. Almost the same high predictability was obtained by using only two CKB values-recorded at admission and within 12 h after admission-or by using just the latter one. Neural networks and quadratic discriminant analysis performed similarly, but the neural networks were more robust for combinations with many laboratory data.
Large discrepancy between prostate-specific antigen results from different assays during longitudinal follow-up of a prostate cancer patient
Authors: Van Duijnhoven H L , Péquériaux N C , Van Zon J P , Blankenstein M A
Published: January 2020

A case is presented of a patient with stage D prostatic carcinoma, from whom a serum sample proved to be an outlier in a correlation study performed with a 2nd-generation prostate-specific antigen (PSA) assay on the Immulite system (6.4 micrograms/L) and IMx (101 micrograms/L). Clearly, the PSA result reported by Immulite was falsely low. For nine longitudinal samples, Immulite results were approximately 20-fold lower than the IMx value (range of IMx results 5-275 micrograms/L). A selection of the samples was analyzed with the ACS:180, ES-600, and IMx (all > 180 micrograms/L); Immulite, DPC Coat-A-Count IRMA, Immuno 1, AIA-pack, and Tandem-R (all <70 micrograms/L); and Immulite free PSA assay (41 micrograms/L). Gel filtration demonstrated that apart from the alpha1-antichymotrypsin (ACT) complex, no other complexes were found. However, the sample consisted of 53% free PSA (IMx). Possibly, a change of conformation of the PSA molecule resulted in a decreased binding to ACT and a reduced affinity of the antibodies used in the affected assays.
Clinical validation of renin monoclonal antibody-based sandwich assays of renin and prorenin, and use of renin inhibitor to enhance prorenin immunoreactivity
Authors: Derkx F H , de Bruin R J , van Gool J M , van den Hoek M J , Beerendonk C C , Rosmalen F , Haima P , Schalekamp M A
Published: January 2020

Newly developed IRMAs to measure the plasma concentrations of renin and prorenin were validated for clinical use and compared with a classical enzyme kinetic assay. The IRMAs involve two monoclonal antibodies, one that reacts equally well with renin and prorenin and one that recognizes renin well but prorenin only minimally. Prorenin reactivity with the second antibody was enhanced by adding the renin inhibitor, Remikiren, to plasma. The complex of prorenin with this active-site ligand undergoes a conformational change, whereby prorenin is converted into a form that cannot be differentiated from renin by the IRMA. The linear working range of the assay was 4.0-3000 mU/L. The concentration of prorenin was calculated by subtracting the assay result obtained without Remikiren (i.e., renin) from the result obtained with Remikiren (i.e., renin plus prorenin). No more than 2% of prorenin present in plasma was detected as renin. The interassay CVs for renin quantification were 18%, 13%, and 8% at low, medium, and high concentrations, respectively. The interassay CV for calculated prorenin was 8% at both low and high concentrations. The IRMA results were highly correlated with those of an enzyme kinetic assay in healthy subjects; in patients with such conditions as primary hyperaldosteronism, renovascular hypertension, and low-, medium-, and high-renin essential hypertension; and in women undergoing gonadotropin stimulation.
High serum IgA concentrations in patients with diabetes mellitus: agewise distribution and relation to chronic complications
Authors: Rodriguez-Segade S , Camiña M F , Carnero A , Lorenzo M J , Alban A , Quinteiro C , Lojo S
Published: January 2020

In this study we investigated the agewise distributions of serum IgA concentrations in 1251 type 1 and 2224 type 2 diabetic patients, and the association between serum IgA concentration and diabetic complications (retinopathy, neuropathy, nephropathy, macroangiopathy, and hypertension). The IgA concentrations of all groups of diabetic patients were significantly higher than those of the corresponding subgroups of 943 control subjects, except for type 1 patients >60 years of age. High IgA concentrations were found in 23.1% of the whole diabetic group. The prevalence of high IgA was significantly greater in males than in females among type 1 patients (24.4% vs 18%). In conclusion, an increase in circulating IgA concentrations is a generalized phenomenon among diabetic patients; IgA concentrations above the reference range are more common among male than female diabetics; and diabetic complications are associated with a significant increase in serum IgA concentration.
One-step all-in-one dry reagent immunoassays with fluorescent europium chelate label and time-resolved fluorometry
Authors: Lövgren T , Meriö L , Mitrunen K , Mäkinen M L , Mäkelä M , Blomberg K , Palenius T , Pettersson K
Published: January 2020

The availability of an intrinsically fluorescent, inert, and stable Eu chelate label made it feasible to design one-step all-in-one immunoassays with time-resolved fluorometry for detection. Both competitive and noncompetitive immunoassays are performed in microtitration wells containing all assay-specific components in a stable dry form. Only the sample and one assay buffer common for all analytes need to be added. Model assays for human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP), and progesterone all reached equilibrium in 15 min or less without compromising the performance characteristics of the measurements, all of which perform at least equivalent to state-of-the-art assays. The detection limits for hCG, AFP, and progesterone were 0.3 IU/L, 0.1 microgram/L, and 0.5 nmol/L, respectively. The assay ranges for hCG and AFP were linear to 5000 IU/L and 1200 micrograms/L, respectively. The immunoassay format can be readily implemented in a fully automated random-access immunoassay system with optimal performance characteristics and no handling of analyte-specific assay components.
New enzymatic assay for calcium in serum
Authors: Kimura S , Iyama S , Yamaguchi Y , Hayashi S , Fushimi R , Amino N
Published: January 2020

We established a simple and rapid kinetic assay for measurement of calcium in serum by using urea amidolyase (EC 3.5.1.45) from yeast species. The method is based on inhibition of the enzyme by calcium. In the assay, we eliminated endogenous ammonium ion by use of glutamate dehydrogenase (GLDH; EC 1.4.1.4); then in the presence of urea amidolyase, urea, ATP, bicarbonate, magnesium, and potassium ions, ammonium ion production was inversely proportional to calcium ion concentration in serum. The concentration of ammonium ion formed was determined by adding GLDH to produce NADP+ in the presence of 2-oxoglutarate and NADPH; we then monitored the change of absorbance at 340 nm. The within-run CVs of this method were 1.7-3.2% (n = 10) at 1.53-3.08 mmol/L, respectively. Day-to-day (total) CVs were 2.8-4.1%. Analytical recovery was 92-112%. The presence of other ions, ascorbic acid, reduced glutathione, bilirubin, hemoglobin, citrate, lipemic material, or human serum albumin did not affect this assay system. The correlation between values obtained with our method (y) and o-cresolphthalein complexone method (CPC) (x) was: y = 1.001x + 0.077 mmol/L (r = 0.949, Sy[symbol: see text]x = 0.079, n = 100); with the other enzymatic method (x) it was: y = 0.952x + 0.021 mmol/L (r = 0.955, Sy[symbol: see text]x = 0.074, n = 100). The SEs for each method were: 0.025 mmol/L, our method; 0.023 mmol/L, CPC method; and 0.025 mmol/L, the other enzymatic method.
Automated assay of plasma bromide after a single deproteinization step
Authors: Jennings G , Elia M
Published: January 2020

This study aimed to simplify the spectrophotometric fluorescein method for measuring plasma bromide, improve its reproducibility, and automate it. After major modifications of the method, we obtained an essentially linear calibration curve for plasma concentrations of bromide between 0 and 5.0 mmol/L. The intraassay CV for measuring bromide in the supernatants of deproteinized plasma samples (initial plasma concentrations 2.5-5.0 mmol/L) was as low as 0.5-1.0% (n = 9). When all the procedures were incorporated, including deproteinization and dilution of plasma, the intraassay CV was 2% at 2.5 mmol/L (n = 5) and 1% at 5.0 mmol/L (n = 5). The interassay CV for measuring bromide in plasma supernatants (initial plasma bromide concentration > 2.5 mmol/L) was 1%. Analytical recovery of bromide added to plasma was 99.1% +/- 2.5%. The new method is simpler and more reproducible than other spectrophotometric methods. Conditions for its automation are described.
Concepts in use of high-dose methotrexate therapy
Authors: Treon S P , Chabner B A
Published: January 2020

In cancer chemotherapy, routine monitoring of drug concentrations has been practical only for methotrexate (MTX). The primary setting for pharmacokinetic monitoring of MTX is its use in high doses (HDMTX) for adjuvant therapy of osteosarcoma, for single-agent treatment of intracranial lymphomas, and in combination therapy of childhood leukemia as well as adult and pediatric non-Hodgkin lymphomas. Typically, HDMTX is infused in doses of 3-15 g/m2 over a period of 6-24 h. Precautions must be taken to ensure a high urine flow and an alkaline urine pH, so as to prevent precipitation of MTX in urine. Patients with decreased renal function, advanced in age, and taking nonsteroidal anti-inflammatory drugs or nephrotoxic agents are at increased risk of developing renal dysfunction during MTX infusion, thus being placed at high risk for toxicity. At the end of HDMTX infusion, and periodically thereafter for 24-48 h, drug concentrations are measured to assure that the disappearance rate of MTX from plasma is occurring at a normal rate. Also, at the end of HDMTX infusion, the patient is given leucovorin (5-formyl-tetrahydrofolic acid; LV), which replenishes intracellular stores of reduced folate and attenuates the toxicity secondary to HDMTX. In the presence of inappropriately high concentrations of MTX, routine doses of LV will be ineffective; the dose of LV required must be increased in proportion to the MTX concentration it faces in plasma. In practice, routine monitoring of plasma MTX concentrations allows early detection of abnormal clearance, as well as institution of early and effective countermeasures, including the use of increased and prolonged LV rescue.
Evaluating the impact of exposure to environmental contaminants on human health
Authors: Silkworth J B , Brown J F
Published: January 2020

Humans are exposed daily to low concentrations of many different chemical substances, natural and some man-made. Although many of these substances can be toxic at high levels, typical exposures are far below the effect levels. The responses produced by man-made aromatic hydrocarbon receptor agonists, such as dioxins, polychlorinated dibenzofurans, coplanar polychlorinated biphenyls, and polycyclic aromatic hydrocarbons, are also produced, often to greater extents [corrected], by naturally occurring constituents of fried meat, cabbage, broccoli, cauliflower, cocoa, and curry. Our society seems to be concerned about the health risks associated only with the synthetic chemicals, regardless of their proportional contribution to the total agonist activity, and regulates on the basis of such concerns. It would be more protective of the public health to determine acceptable concentrations for each type of response, regardless of the origin of the inducing agent, and issue advisories or regulations accordingly.
Molecular and immunological detection of circulating tumor cells and micrometastases from solid tumors
Authors: Pelkey T J , Frierson H F , Bruns D E
Published: January 2020

Histological, immunological, and molecular methods have been used for detecting micrometastases from nonhematopoietic malignancies. Early studies utilizing cytological methods to identify circulating tumor cells demonstrated the uncertain significance of micrometastasis detection for predicting eventual recurrent disease. Recently, reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of circulating tumor cells has been suggested as a potential technique for staging of cancer. Studies using RT-PCR thus far indicate that test results may be negative in some patients with known metastatic disease, thereby raising doubts about the utility of the method for staging of disease. In this review, we survey the relevant literature and discuss the range of current applications of histological, immunological, and molecular methods for detecting micrometastases from solid tumors in blood, bone marrow, and lymph nodes and the progress toward determining the significance of micrometastasis detection.
Direct quantification of pentosidine in urine and serum by HPLC with column switching
Authors: Takahashi M , Hoshino H , Kushida K , Kawana K , Inoue T
Published: January 2020

Concentrations of pentosidine, an advanced glycation end product, are increased in aging, diabetes mellitus, and uremia. Using HPLC with column switching, we developed a direct method of measuring pentosidine in urine and serum. We inject the sample directly onto a gel-filtration precolumn, select ("heart-cut") the eluate fraction containing pentosidine, and introduce this fraction into a reversed-phased column by use of a switching valve. The recovery rate of the complete method was 97.7-99.9%. The intraassay CV was 5.7%, and the interassay CV was 5.8%. The calibration curve showed significant linearity (r = 0.998, P = 0.0001). We examined urinary concentrations of pentosidine in 12 diabetic patients (mean +/- SD, 8.7 +/- 2.3 micromol/mol of creatinine), 32 patients with chronic renal failure (CRF; 36.1 +/- 39.0), 19 osteoporotic patients (7.9 +/- 5.3), and 29 healthy control subjects (5.2 +/- 2.3). In CRF, urinary pentosidine in the patients undergoing hemodialysis was significantly higher than in CRF patients not being treated by hemodialysis (mean, 58.1 vs 18.2; P <0.001). Also, concentrations of urinary and serum pentosidine were significantly correlated (r = 0.797, P = 0.0011). Because this method does not require pretreatment of samples, it is convenient and useful for measuring urinary and serum pentosidine.
Ciba Corning ACS:180 testosterone assay evaluated
Authors: Wheeler M J , D'Souza A , Matadeen J , Croos P
Published: January 2020

A fully automated direct assay of testosterone has been developed for the Ciba Corning ACS:180 immunoassay system. We have evaluated this method and compared specimen results with those from the Diagnostic Products Corp. (DPC) and Medgenix direct assays and an in-house extraction assay. Accuracy of the method was assessed by measuring GC-MS-targeted serum pools. Within-assay im- precision was <6% and between-assay imprecision <9% over the concentration range examined. High concentrations of lipid caused an increase in the measured testosterone but other potential interferents were without effect. Recovery was quantitative but was affected by sex-hormone-binding globulin. The method was positively biased with respect to the DPC and Medgenix assays but negatively biased with the extraction assay. Measurement of the GC-MS-targeted serum pools showed the assay to overestimate recovery by approximately 13%. The ACS:180 assay is particularly attractive as a routine assay because it is fully automated, obtains the first result in only 15 min, and shows good assay performance.
Fluoroenzymometric method to measure cardiac troponin I in sera of patients with myocardial infarction
Authors: Zaninotto M , Altinier S , Lachin M , Carraro P , Plebani M
Published: January 2020

The aim of our study was to evaluate the clinical relevance of serum troponin I (TnI) as a marker of ischemic myocardial injury by using an automated fluoroenzymometric assay. The reference range for serum TnI was established by measuring serum TnI concentrations in blood from 75 healthy donors. The concentration was then compared with serum creatine kinase (CK) activity, CK-MB mass, and myoglobin concentrations in 20 patients with myocardial infarction diagnosed according to the WHO criteria, 20 patients with chest pain of nonischemic origin, 9 patients with unstable angina, 11 with stable angina, 11 patients with chronic muscular diseases, 6 patients with muscular trauma without chest contusion, and 13 patients with chronic renal disease. We found that: (a) 99% of the blood donors had TnI concentrations <0.26 microgram/L (detection limit of the assay in our study); (b) TnI values in acute myocardial infarction (AMI) patients 4 h after onset of chest pain showed a sensitivity of 0.769 and a specificity of 1.0 at a decisional concentration for AMI of 1 microgram/L, even in the presence of severe skeletal muscle injuries or renal diseases; (c) the increase in TnI concentrations after infarction (interquartile range 3.25-6 h) and the peak occurred later (interquartile range 11.5-24 h) than the rise found in myoglobin and CK-MB, but the increase persisted much longer (>96 h); (d) receiver-operating characteristic curve analysis showed the high diagnostic accuracy of TnI in diagnosing AMI even in patients in whom traditional biochemical markers are adversely influenced by underlying clinical situations.
The impacts of climate change on the biomechanics of animals
Authors: Domenici Paolo , Seebacher Frank
Published: January 2020

Anthropogenic climate change induces unprecedented variability in a broad range of environmental parameters. These changes will impact material properties and animal biomechanics, thereby affecting animal performance and persistence of populations. Climate change implies warming at the global level, and it may be accompanied by altered wind speeds, wave action, ocean circulation, acidification as well as increased frequency of hypoxic events. Together, these environmental drivers affect muscle function and neural control and thereby movement of animals such as bird migration and schooling behaviour of fish. Altered environmental conditions will also modify material properties of animals. For example, ocean acidification, particularly when coupled with increased temperatures, compromises calcified shells and skeletons of marine invertebrates and byssal threads of mussels. These biomechanical consequences can lead to population declines and disintegration of habitats. Integrating biomechanical research with ecology is instrumental in predicting the future responses of natural systems to climate change and the consequences for ecosystem services such as fisheries and ecotourism.
The SSP 2020: The Revised School Success Profile
Authors: Bowen Natasha K , Lucio Robert , Patak-Pietrafesa Michele , Bowen Gary L
Published: January 2020

To support student success effectively, school teams need information on known predictors of youth behavior and academic performance. In contrast to measures of behavioral and academic outcomes that are commonly relied on in schools, the School Success Profile (SSP) for middle and high school students provides comprehensive information on predictors of outcomes that reside in students’ neighborhoods, schools, peer systems, and families. This article presents the SSP 2020, a newly revised version of the SSP that is now freely available to schools and researchers. The online, self-report SSP 2020 retains the strengths of the SSP but is shorter and simpler. Revised group- and individual-level reports are automatically generated once SSP data are collected. The SSP 2020 dashboard allows users to request reports on numerous demographic subgroups. A comprehensive prevention road map walks teams through each step of an evidence-informed decision-making process based on SSP 2020 data. Resources embedded in the road map include information on evidence-informed prevention strategies for SSP dimensions with corresponding brief assessments and fidelity checklists. School social workers are encouraged to take the lead in bringing the SSP 2020 to school teams charged with promoting student behavioral and academic success.
63 Effect of 100-km ultramarathon on N-terminal pro-B-type natriuretic peptide variation
Authors: How C , Li L , Kao W
Published: January 2020

Introduction

The change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels follows strenuous endurance exercise-imposed paradox. Our previous reports showed significant body weight (BW) loss with dehydration was common in ultramarathon runners. The aim of this study is to investigate whether the dehydration and renin-angiotensin-aldosterone system activation possibly contribute to exercise-induced NT-proBNP release.

Methods

Twenty-six participants who finished a 100-km ultramarathon in Taiwan were enrolled. For each participant, blood samples and spot urine samples were collected one week before the race, as well as immediately and 24 hours after the finish. Body weight change was recorded to monitor the hydration status.

Results

Prolonged endurance exercise led to a substantial increase in NT-pro-BNP. Compared to pre-race values, NT-pro-BNP levels significantly increased immediately after the race (24.3 ± 20.2 to 402.9 ± 305.9 pg/mL, p < 0.05) and maintained the lasting high levels till 24 hours after the race finished (143.7 ± 126.1 pg/mL, p < 0.05). The fractional excretion of sodium values were all below 1% in three different time points. The 100-km ultramarathon resulted in significant BW loss, and elevated of renin and aldosterone levels. However, only 24 hours after the race, there was a positive significantly relationship between NT-proBNP and aldosterone levels, but negative significantly relationship between NT-proBNP and BW increase during the recovery phase.

Conclusions

Results of this study showed the mechanism of NT-proBNP release immediate following the race were multifaceted. However, during the recovery phase, rehydration might lead to the decrease of NT-proBNP in the volume depletion state.
66 Simple bedside cardiovascular autonomic examinations for predicting chronotropic incompetence
Authors: Rusnanta F , Rizal A
Published: January 2020

Background

Simple bedside cardiovascular autonomic reflex test (CARTs) are usually used to determine cardiovascular autonomic neuropathy (CAN). CAN may contribute to chronotropic incompetence (CI) which is the inability of the heart rate (HR) to rise in proportion to an increase in metabolic demand. Determination of CI is widely based on measurement of maximum HR during exercise testing. This study aimed to evaluate the role of CARTs to determine CI.

Methods

We included in 105 patients using a derivation and validation sampling ratio of 2:1. CARTs were performed for analyzing heart rate variation during three parasymphathetic standard tests (deep breathing, lying to standing, Valsava maneuver) and two sympathetic standard tests (systolic blood pressure from lying to standing and diastolic blood pressure during handgrip maneuver). Variables independently associated with CI in multivariable analysis in the derivation set were assigned points based on their respective odds ratios.

Results

CI group showed significantly lower values of among three parasympathetic standard tests (p < 0.05) but not significantly among two sympathetic standars tests. Valsava maneuver (OR 0.1, p < 0.001, 95%CI 0.001-0.004), deep breathing (OR 0.91, p = 0.025, 95% CI 0.836-0.988), and handgrip maneuver (OR 0.85, p = 0.01, 95% CI 0.744-0.961) were found to be an independent risk factor for CI from multivariate regression analysis. The accuracy of different CART parameters in the prediction of CI was described by the receiver operating curve (ROC) analysis. Regarding logistic regression model, we constructed formula of 15 - ([12 x Valsava maneuver] + [0.1 x deep breathing] + [0.2 x handgrip maneuver]) which will show negative and positive results indicating CI and non-CI, respectively. The resulting score showed good calibration and discriminatory capacity in the derivation (Hosmer-Lemeshow x² 10.051, p = 0.186, AUC = 0.878). The difference between AUCs in the derivation and validation sets was Δ =  0.122 (p = 0.174).

Conclusion

The decrease in heart rate variations during Valsava maneuver and deep breathing and in diastolic blood pressure during handgrip maneuver seems to be related to development of CI. Formula of CARTs score is a useful tool for predicting CI.

Final score sheet based on formula Total score CI probability <-0.1 High probaility 0.2-0.6 Intermediate probability >0.6 Low probability
149 Acute effects on left ventricular systolic and diastolic function of a post-implant echocardiographic biventricular pacemaker optimization protocol following cardiac resynchronization therapy
Authors: Barbier P , Guglielmo M , Agalbato C , Viscone I , Savioli G
Published: January 2020

Background

Cardiac resynchronization therapy (CRT) has demonstrated efficacy in at least 60% of patients with left ventricular (LV) failure and guideline-based indication to CRT. Whereas lack of response to CRT in up to a third of patients is multifactorial, a relevant factor is thought to be inadequate biventricular pacemaker (BIV) optimization (OPT) of either the intraventricular (VVd) or atrioventricular (AVd) delay

Purpose

In this echocardiographic observational study, we compared the acute effects on LV contractility, output, and diastolic function of BIV intra-implant QRS duration-based (OPTq) and post-implant Doppler echocardiography-based (OPTe) OPT of VVd and AVd.

Methods

In 160 patients with ischemic (n = 86) or idiopathic (n = 74) dilated cardiomyopathy, guideline-based different de novo CRT systems were implanted followed by immediate OPTq. Post-implant (10 days) OPTe was performed measuring: transmitral velocity-time integral (MVFi), % diastolic filling time (MVFt%), and E/A ratio, LV outflow integral (LVOTi), ejection time (LVOTt), and stroke volume (SV), isovolumic contraction (IVCT) and relaxation (IVRT) times, and LV myocardial performance index (MPI). The protocol included, sequentially: 1) Doppler measurements with OPTq settings; 2) measurements (separated by 3’ intervals) during a range (80/200 ms) of AVd with synchronous VVd; 3) algorithm-based AVd selection (at least 2 of following: increase in MVFi or SV, decrease in MPI); 4) measurements, with set AVd, during range of VVd: LV-first (-20, -40ms); RV-first (20, 40ms); synchronous; 5) VVd selection based on same algorithm used for AVd selection. Results. At OPTq, 58.6% of patients were set synchronous, 38.6% LV-first and 3% RV-first, with a 126 ± 29 mean AVd. This increased to 137 ± 36 after OPTe, when 49.1% were set synchronous, 38% LV-first and 12.4% RV-first, resulting in modifications of AVd and VVd in 59% and 36% of patients. Further, gain in SV with OPTe, compared to OPTq, was 8.3% (p<.001), paralleled by an increase in MVFi (21.2 ± 8 cm vs 20.5 ± 8, p<.001) and decrease in E/A (1.25 vs 1.45, p<.001). The greatest increase in SV with OPTe was found in patients in whom both AVd and VVd were modified (n = 48; 81 ± 26 ml vs 71 ± 23, p<.001) vs. patients without modifications (n = 42), or with change of either AVd or VVd (n = 70; 77 ± 20 vs 72 ± 20, p<.01). Only in the first patient group both MVFi (22 ± 9 vs 20 ± 9, p<.001) and MVFt% (52 ± 7 vs 49 ± 8, p=.004) increased, along with a decrease in MPI (.82±.31 vs .92 ± 36, p=.007) and IVRT (144 ± 51 vs 156 ± 62, p=.02.

Conclusions

These preliminary results point to a significant incremental role of post-implant OPTe to enhance LV output, contractility, and diastolic function in patients with CRT. The prognostic role of OPTe-determined AVd and VVD changes remains to be determined.
P13 Safety and efficacy of sacubitril-valsartan initiation during and after acute decompensated heart failure with reduced ejection fraction
Authors: Tan C T , Koh K T , Onn Y Y , Ho K H , Said A , Mohd Amin N H , Shu F E P , Khiew N Z , Cham Y L , Fong A Y Y , Ong T K , Eng S Y , Lee Z Y , Madzlan N
Published: January 2020

Background

The PIONEER-HF trial has demonstrated the safety of Sacubitril-Valsartan initiation during acute decompensated heart failure (ADHF) compared to Enalapril. The efficacy outcome was also addressed by the surrogate end point of reduction in NT-proBNP. However, the safety and efficacy of Sacubitril-Valsartan initiation during ADHF compared to initiation after ADHF was unknown.

Objectives

(1) To compare the safety and efficacy of Sacubitril-Valsartan initiation during ADHF(inpatient) to initiation after ADHF(outpatient). (2) To explore the echocardiogram parameters associated with Sacubitril-Valsartan initiation during ADHF(inpatient) versus after ADHF(outpatient).

Methods

We enrolled patients diagnosed with heart failure with reduced ejection fraction (HFrEF) initiated on Sacubitril-Valsartan from February 2017 to December 2018. The baseline characteristics, echocardiogram parameters (changes in LVEF and positive remodeling), composite safety outcomes (hypotension, interruption of Sacubitril-Valsartan and worsening of renal function), and efficacy outcomes (cardiac death, readmission for heart failure) were compared.

Results

Thirty-seven patients were identified out of which 21 patients started Entresto after ADHF (outpatient group) and 16 patients during ADHF (inpatient group). The median follow-up duration was 196 days (IQR: 105 to 328days). The baseline characteristics were similar between the 2 groups. Outpatient groups achieved a significantly higher maximally tolerable dose of Sacubitril-Valsartan compared to inpatient group (median 400mg/day versus 200mg/day, p = 0.008) despite a similar starting dose (median 100mg/day versus 100mg/day, p = 0.127). The composite efficacy outcomes were similar between the 2 groups (4.8% versus 18.8%, p = 0.296). The composite safety outcome was similar between the groups (18.8% versus 4.8%, HR5.70 p = 0.054, 95%CI 0.967 to 33.60). Both groups achieved a significant improvement in LVEF after initiation of Sacubitril-Valsartan therapy: mean LVEF 23.44 ± 7.88% to 34.30 ± 13.88% (p = 0.001) in outpatient group; mean LVEF 22.99 ± 11.31% to 38.81 ± 13.91% (p = 0.002) in inpatient group. Reverse remodeling (reduction of LVESV≥15%) was similar between the 2 groups (61.9% versus 50.0%, p = 0.506).

Conclusions

Among patients with HFrEF in ADHF, initiation of Sacubitril-Valsartan therapy during or after ADHF led to similar safety and efficacy. Overall, there was a significant improvement in LVEF and positive remodeling of the LV regardless of the timing of initiation of therapy.
P14 Use of bromocriptine for the treatment of peripartum cardiomyopathy: a meta-analysis of randomized controlled trials
Authors: Villanueva D L , Villanueva M C , Llanes E J
Published: January 2020

Background

Peripartum cardiomyopathy is a rare, pregnancy associated cause of left ventricular heart failure in previously healthy women. It remains an important cause of cardiac-related maternal morbidity and mortality worldwide. Half of the patients will recover left ventricular function after 6 months. However, in the remainder of patients who do not recover cardiac function, they will require advanced heart failure therapies. Bromocriptine, a dopamine agonist which inhibits prolactin release, has demonstrated improvement in left ventricular recovery and clinical outcome. We sought to determine the effect of adding Bromocriptine to standard heart failure therapy on the improvement and recovery of left ventricular function of these patients.

Inclusion Criteria. Studies were included if they satisfied the following criteria:1) Randomized Controlled Trials; 2) Pregnant patients who fulfilled the criteria for diagnosis of peripartum cardiomyopathy and 3) Reported data on improvement in left ventricular ejection fraction and clinical outcomes.

Methods

  Using PUBMED, Clinical Key, Science Direct, Scopus, and Cochrane databases, a search for eligible studies was conducted from June to December 31, 2018. The quality of each study was evaluated using the Cochrane Risk of Bias Tool. The primary outcome of interest is on the effect of Bromocriptine on the improvement of left ventricular function and clinical outcomes among these patients. Review Manager 5.3 was utilized to perform analysis of random effects for continuous outcomes.

Results

We identified 2 randomized controlled trials of 58 pregnant patients diagnosed with peripartum cardiomyopathy, showing that among those who received Bromocriptine on top of standard heart failure therapy, there is a significant improvement in the left ventricular ejection fraction at 6 months [mean difference 15.14 (95% CI, 6.53 to 23.75) p <0.05] compared to standard heart failure therapy alone. It was also observed that those who received Bromocriptine had better clinical outcomes.

Conclusion

The addition of Bromocriptine on top of standard heart failure therapy significantly improved the left ventricular ejection fraction of patients with peripartum cardiomyopathy at 6 months post-partum. This novel therapy may be considered to improve the management of these patients.
P26 Soluble programed cell death ligand-1 is associated with acute coronary syndrome
Authors: Fujisue K , Yamamoto E , Sueta D , Takae M , Nishihara T , Oike F , Komorida T , Usuku H , Takashio S , Sakamoto K , Kaikita K , Tsujita K
Published: January 2020

Background

Immune checkpoint by programmed cell death (PD)-1 and its ligand (PD-L1) play crucial role in T cell tolerance toward vascular wall antigens. PD-L1 is widely expressed on a number of cells including immune cells and vascular endothelium. It was reported that increased expression of PD-L1 in dendritic cells implicates upregulated inflammation in atherosclerotic lesions that is associated with plaque instability. Although plaque rupture in coronary atherosclerosis is an important pathogenesis of acute coronary syndrome (ACS), the association between PD-L1 and ACS is still unknown.

Purpose

We hypothesize that circulating PD-L1 might be associated with ACS, reflecting endothelial damage and coronary plaque rupture. To elucidate this hypothesis, we compared serum levels of soluble PD-L1 (sPD-L1) in stable coronary artery disease (CAD) patients with those in ACS patients.

Methods

Serum levels of sPD-L1 were measured by using commercially available ELISA kit (Human PD-L1/B7-H1 DuoSet, R&D Systems) in consecutive patients with CAD admitted to our University Hospital from February 2016 to March 2017. Patients with any malignant disease or severe inflammatory disease were excluded from this study. Serum levels of sPD-L1 and clinical backgrounds were compared between stable-CAD and ACS patients.

Results

In total, 269 patients with CAD were enrolled (28 cases [10.4 %] with ACS and 241 cases [89.6 %] with stable-CAD). PD-L1 had no correlation to C-reactive protein, cardiac troponin, and classical atherosclerotic risks such as age, body mass index, estimated glomerular filtration rate, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, and hemoglobin A1c. Although age, sex, history of smoking, and the prevalences of hypertension, diabetes mellitus and dyslipidemia were comparable between both groups, the level of LDL-C was significantly higher in patients with ACS compared with those with stable-CAD (94.0 [77.0–112.0] mg/dL vs. 78.5 [65.0–97.0] mg/dL, P = 0.008). Also serum level of sPD-L1 was significantly increased in patients with ACS compared with those with stable-CAD (106.1 [60.9–157.7] pg/mL vs. 64.8 [30.9–102.5] pg/mL, P = 0.003). Univariate logistic regression analysis identified that serum levels of both sPD-L1 and LDL-C were independently associated with ACS. Moreover, multivariable logistic regression analysis with factors from univariate analysis identified that serum level of sPD-L1 was significantly and independently associated with ACS (odds ratio: 1.006, 95 % confidence interval: 1.001–1.012, P = 0.03).

Conclusions

This is the first study to elucidate that the increased serum levels of sPD-L1 was associated with ACS. This study suggests that sPD-L1 could be a risk marker and therapeutic target for ACS.
P32 Do meteorological factors influence the occurrence of acute aortic dissection?A ten-year retrospective institutional review
Authors: Usui R , Yoshizumi T , Oshima H , Usui A
Published: January 2020

Purpose

Some studies have reported a relationship between meteorological factors and the occurrence of acute aortic dissection (AAD). Nevertheless, the results of the studies are heterogeneous. Furthermore, whether the absolute values or fluctuation of meteorological factors influence the occurrence of AAD remains controversial. The aim of this study was to determine the meteorological factors associated with the occurrence of AAD.

Methods

Two hundred eighty-two consecutive patients (male, n = 178; female, n = 104; average age, 68 years) admitted to our hospital for AAD in the 10 years from September 1st 2008 were included in this study. One hundred fifty-seven patients had type A dissection. The correlation between the clinical data and the local meteorological data over the same period (provided by the National Meteorological Agency) was analyzed. We compared the following factors on days of AAD occurrence and non-occurrence: minimum and maximum temperature, minimum and maximum temperature difference between day of occurrence and previous day, difference between maximum and minimum temperature, atmospheric pressure and atmospheric pressure difference between day of occurrence and previous day (Δatmospheric pressure), and minimum and maximum temperature difference from climatological standard normal (CSN). Cutoff values were determined by ROC curve analyses and odds ratios (ORs) were calculated by a logistic regression analysis of meteorological factors with statistically significant differences.

Results

ignificant differences between the days of AAD occurrence and non-occurrence were observed for minimum and maximum temperature (p < 0.0001), atmospheric pressure (p < 0.0001) and Δatmospheric pressure (p = 0.0286), minimum temperature difference from CSN (p < 0.0001), and maximum temperature difference from CSN (p = 0.0010).

The cutoff values were as follows: minimum temperature, 4°C; maximum temperature, 15.1°C; atmospheric pressure, 1008.9hPa; Δatmospheric pressure, 0.4hPa; minimum temperature difference from CSN, 1°C; and maximum temperature difference from CSN, -0.2°C.

The univariate logistic regression model showed revealed the following significant predictors of the occurrence of AAD; minimum temperature (OR2.42, p < 0.0001), maximum temperature (OR2.23, p < 0.0001), air pressure (OR1.75, p < 0.0001), Δatmospheric pressure (OR 1.44, p = 0.0030), minimum temperature difference from CSN (OR1.80, p < 0.0001) and maximum temperature difference from CSN (OR1.58, p = 0.0003). However, only minimum temperature (OR1.60, 95% CI 1.00-2.53, p = 0.0478) and maximum temperature difference from CSN (OR1.45, 95% CI 1.11-1.89, p = 0.0062) remained significant in the multivariate analysis.

Conclusion

Meteorological factors, especially a minimum temperature under 4°C strongly influenced the occurrence of AAD. A maximum temperature difference from CSN of over -0.2°C was also a significant predictor of AAD.
P108 Clinical effect of tricuspid regurgitation caused by pacemaker lead
Authors: Shaikh M M , Aljabri S , Nadar S K
Published: January 2020

Aim

It is known that the presence of cardiac pacemaker leads across the tricuspid valve (TV) can lead to tricuspid regurgitation (TR). However the clinical implications of this are not known. The aim of this study was to evaluate the progression of TR in patients with pacemaker leads across the TV and assess the clinical effect on Right ventricular function.

Methods

Patients who had undergone cardiac device implantation (either pacemaker or implantable cardiac defibrillators) in our institution over a 5 years period were identified. Those who had an echo (for any indication) pre and post device implantation were included in this study and their data assessed. Clinical information was obtained from medical records

Results

A total of 65 patients (mean age 70 + 13 years, 31 (48%) male and 34 (52%)female)  were enrolled in the study. The median follow up after implantation was 12 (12-24) months. At baseline 29 patients had TR before implantation which increased to 51 (78%) during follow up, indicating that 22 patients developed new TR. Of those with pre existing TR,  17 had  worsening of TR by at least one grade. RV function as measured by TAPSE had decreased from 1.87+ 0.44 to 1.68 +0.42 p = 0.002 . Six patients developed RV dilatation during follow up. 18 patients had developed signs of Right heart failure (either breathlessness with raised jugular venous pressure or pedal oedema or both), of which 13 had only new pedal oedema. There was no difference in comorbidities or the percentage of pacing in the groups that had worsening of TR or RV dilatation.

Conclusion

There is definite worsening or development of new TR in patients with a pacing lead across the TV. This is associated with an increase in the incidence of right heart failure suggesting that this is not benign. However there does not appear to be any specific risk factor identified that is responsible for this.

Changes after pacemaker implantation Pre pacemaker Post pacemaker p value Presence of TR (n) 29 51 0.018 RV dilatation(n) 5 11 0.01 TAPSE (mm) 1.87 + 0.44 1.68 + 0.42 0.002 Presence of pedal oedema(n) 5 13 0.01 TR grade grade 0 Grade 1 Grade2 Grade 3 Grade 4 36 9 16 3 0 14 3 31 16 2 0.008 TR- tricuspid regurgition, TAPSE- Tricuspid annular plane systolic excursion; RV- right ventricle
P251 Fragmented QRS in prediction of ischemic heart disease diagnosed by stress cardiovascular magnetic resonance imaging
Authors: Yooprasert P , Vathesatogkit P , Thirawuth V , Prasertkulchai W , Tangcharoen T
Published: January 2020

Funding Acknowledgements

None

Background

Fragmented QRS complex (fQRS) on 12-lead EKG is not uncommon in general population. Previous studies found an association between fQRS and myocardial scar, heart failure, and increased cardiac mortality. However, data in adults without history of coronary artery disease is limited. We aimed to evaluate whether there is an association between fQRS and ischemic heart disease (IHD) diagnosed by stress cardiac MRI.

Method

We retrospectively reviewed data from 604 patients who underwent stress cardiac MRI, in which 50 patients were excluded due to known history of coronary artery disease or incomplete stress test. A positive result was defined as stress-induced perfusion defect in at least 2 contiguous myocardial segments corresponding to epicardial coronary territory, or a presence of ischemic scar. The 12-lead EKG done on the same day with MRI, prior to stress testing, were analyzed. Fragmented QRS was defined as the presence of additional R wave (R’), notching in the nadir of R or S wave, or the presence of more than one R’ in any EKG leads. Both cardiac MRI and EKG were analyzed by two independent observers.

Result

 

Final analysis included 554 patients, 39% were male, with a mean age of 67.8 ± 11.1 years. There was positive stress cardiac MRI in 219 patients (39.5%). Older age, diabetes mellitus, and hypertension were more frequent in the positive group (p <0.05). fQRS was identified in 300 patients (54.2%). Baseline characteristic did not differ significantly between patients with and without fQRS. There is an association between fQRS and IHD, OR 1.605 (95% CI 1.136-2.269), p = 0.007. Using linear regression, the number of leads with presence of fQRS showed an association with IHD (OR 1.204, p = 0.005). After adjustment for age, diabetes, hypertension, renal function, and left ventricular ejection fraction, the strong association between fQRS and IHD persisted, OR 1.709 (95% CI 1.182-2.470), p = 0.004.

Conclusion

In patients without known history of coronary artery disease, fragmented QRS is independently associated with ischemic heart disease diagnosed by stress cardiac MRI.

Multiple regression analysis OR 95% CI p-value Age (years) 1.013 0.992 - 1.035 0.234 Diabetes mellitus 1.532 1.032 - 2.274 0.034 Hypertension 1.194 0.737 - 1.935 0.471 GFR (ml/min/1.73m²) 0.999 0.987 - 1.011 0.904 LV ejection fraction (%) 0.972 0.950 - 0.994 0.014 fragmented QRS 1.709 1.182 - 2.470 0.004