Abbott Laboratories Research Articles

Establishment of trimester-specific reference intervals of renal function tests and their predictive values in pregnant complications and perinatal outcomes: A population-based cohort study

ObjectivesIn this study, we aimed to establish the trimester-specific RIs of renal function tests (RFTs) in singleton pregnant women and investigate the associations between adverse perinatal outcomes and abnormal renal function laboratory results. MethodsThe results of RFTs and the associated medical records were retrieved from 16489 singleton pregnant women who underwent first- and third-trimester prenatal screening and gave a live birth at out institute between August 2018 and December 2019. The RFTs were performed on the automated immunochemistry platform ARCHITECT ci16200 (Abbott Laboratories Ltd, Abbott Park, Illinois, US) in the clinical laboratory of our institute. The nonparametric 2.5th-97.5th percentile intervals and the indirect Hoffmann methods were used to define the trimester-specific RIs. The associations between abnormal RFTs and adverse pregnancy outcomes was assessed statistically by logistic regression. ResultsThere was no significant difference between the direct observational and the indirect Hoffmann methods in establishing RIs of RFTs. Compared with RFTs in the first trimester, the concentrations of serum BUN and Crea were slightly decreased (p < 0.001), and the serum UA and Cys C levels were significantly elevated in the third trimester (p < 0.001). In the logistic regression analysis, high concentrations of UA, Crea, and Cys C in late pregnancy were associated with an increased risk of postpartum hemorrhage. Meanwhile, early pregnancy UA was associated with a modestly increased risk of GDM, GH, and PE. ConclusionIt is necessary to establish trimester-specific RIs for RFTs, in order to appropriately interpret laboratory results and to identify women with high risks of developing various adverse outcomes.

BCL-xL Targeting to Induce Apoptosis and to Eliminate Chemotherapy-Induced Senescent Tumor Cells: From Navitoclax to Platelet-Sparing BCL-xL PROTACs.

Restoring apoptotic cell death is a critical goal for cancer therapy. One of the primary mechanisms by which cancer cells evade death and maintain survival in the face of stress signals is by overexpression of prosurvival B-cell lymphoma 2 (BCL2) family members such as BCL2, BCL-xL, and MCL1, which suppress the intrinsic (mitochondrial) pathway of apoptosis through complex protein and membrane interactions. While these antiapoptotic proteins have been validated as potent therapeutic targets, synthesis of their inhibitors remained challenging for decades mainly due to the presence of a difficult to target, highly hydrophobic groove on the surface. The groove serves as a binding site for the BH3 domain of corresponding proapoptotic partners, which leads to their sequestration and prevents apoptosis. In 2008, a Cancer Research article by Tse and colleagues, led by Dr. Steven Elmore from Abbott Laboratories, reported the discovery of the first orally bioavailable BCL2/BCL-xL inhibitor, navitoclax (ABT-263), marking the onset of an era of "BH3 mimetics" in cancer therapeutics and changing the therapeutic landscape especially for leukemia. Here, we reflect on how this landmark study fueled development of small-molecule BH3 mimetics like venetoclax and seek to indicate new strategies and future directions for improving the clinical activity of navitoclax for hematologic malignancies. See related article by Tse and colleagues, Cancer Res 2008;68:3421-3428.

THU066 An 8-year Interim Report Of The B2412 Study, An Open-label, Multicenter Pasireotide Rollover Study For Patients Who Continued To Receive Benefit From Pasireotide At Completion Of An Earlier Trial

Abstract Disclosure: M. Gadelha: Advisory Board Member; Self; Novo Nordisk, Recordati, Crinetics Pharmaceuticals. Speaker; Self; Recordati, Novo Nordisk, Ipsen, Crinetics Pharmaceuticals. M.D. Bronstein: None. E. Grineva: Advisory Board Member; Self; Ipsen, Merck, Pfizer, Inc. Speaker; Self; Recordati, Ipsen, Pfizer Berlin Chemie, Teva Pharmaceutical Industries Ltd., A. Menarini, Siemens Healthineers. N. Kapoor: None. C. De Block: Consulting Fee; Self; Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, A Menarini Diagnostics, Eli Lilly &amp; Company, Insulet Corporation, Medtronic, Novo Nordisk, Roche Pharmaceuticals. Research Investigator; Self; AstraZeneca, Boehringer Ingelheim, Indigo Diabetes, Novo Nordisk. Speaker; Self; Abbott Laboratories, AstraZeneca, Boehringer Ingelheim, A Menarini Diagnostics, Eli Lilly &amp; Company, Insulet Corporation, Medtronic, Novo Nordisk, Roche Pharmaceuticals. J.M. Escalante Pulido: None. G. Rollin: Advisory Board Member; Self; Merck Serono. Speaker; Self; Novo Nordisk, Abbott Laboratories, AstraZeneca, Merck Serono. R. Baggenstoss: None. A. Piacentini: Employee; Self; Recordati. A.M. Pedroncelli: Employee; Self; Recordati. W. Gallardo: Speaker; Self; Pfizer, Inc., Merck, Ipsen, Novartis Pharmaceuticals. Introduction: A robust clinical development program of 14 trials demonstrated that the second-generation somatostatin receptor ligand, pasireotide, is an effective treatment for patients (pts) with rare endocrine disorders, including acromegaly and Cushing’s disease (CD). Pts with acromegaly or CD have significant morbidity, reduced quality of life and, if inadequately treated, a higher mortality risk than the general population. This 8-year interim analysis evaluated the long-term safety of pasireotide treatment in pts with acromegaly, CD or other endocrine disorders. Methods: This ongoing, open-label, multicenter study allows continued treatment for pts who completed a previous pasireotide parent trial (NCT01794793). Pts who continued to receive clinical benefit, as determined by the investigator in the parent study, entered the rollover study and remained on pasireotide. Depending on the route of administration in the parent study, pts received pasireotide long-acting release (LAR; n=303) or subcutaneous (sc; n=38) as monotherapy (n=36), or sc in combination with cabergoline (n=2). The primary objective was to evaluate long-term safety, determined by frequency of adverse events (AEs)/serious adverse events (SAEs). Results: Overall, 341 pts from 29 countries have entered the study from 14 parent studies; 228 pts had acromegaly, 64 CD and 49 other endocrine disorders, including melanoma, dumping syndrome and neuroendocrine tumors. Median (min−max) exposure to all pasireotide formulations from rollover baseline to data cut-off and across all indications was 45.3 months (0.9−100.8). Median (min−max) dose from rollover baseline was 45.4 mg/month (5.3−128.3) with pasireotide LAR and 1200 µg/day (300−1800) with pasireotide sc. In total, 89 (26.1%) pts discontinued treatment; the most common reason was consent withdrawal (n=21, 6.2%). Most common AEs during rollover (≥10% in all pts) were nasopharyngitis (acromegaly n=13, 5.7%; CD n=14, 21.9%; other diseases n=14, 28.6%), hyperglycemia (acromegaly n=29, 12.7%; CD n=2, 3.1%; other diseases n=7, 14.3%), back pain (acromegaly n=20, 8.8%; CD n=7, 10.9%; other diseases n=8, 16.3%) and headache (acromegaly n=21, 9.2%; CD n=6, 9.4%; other diseases n=7, 14.3%). SAEs were reported in 87 (25.5%) pts; the most common were cholelithiasis and COVID-19 (both n=9, 2.6%). Overall, 18 (5.3%) pts discontinued treatment because of AEs. Incidence of new hyperglycemia-related AEs during rollover was low. No new safety signals were identified. Conclusions: Hyperglycemia is an expected AE during pasireotide treatment, often occurring in the first 3 months of therapy. These data in pts with acromegaly, CD or other endocrine disorders support pasireotide as a well-tolerated long-term treatment and affirm that pts continue to receive long-term benefit, with a low discontinuation rate over 8 years. Presentation: Thursday, June 15, 2023

THU584 Comparison Of The Cardiovascular Benefits Of Bempedoic Acid With Statins- Analysis By The Cholesterol Treatment Trialists’ Methodology

Abstract Disclosure: A. Lincoff: Advisory Board Member; Self; Novo Nordisk, Eli Lilly &amp; Company. Consulting Fee; Self; GlaxoSmithKline, Medtronic, Ardelyx, Akebia, Endologix, Provention Bio. Grant Recipient; Self; Abbvie, Novartis Pharmaceuticals, Esperion, AstraZeneca, CSL Behring. Stock Owner; Self; Cadrenal. K. Ray: Consulting Fee; Self; Amgen Inc, Sanofi, Regeneron, Pfizer, Inc., Viatris, Abbott Laboratories, AstraZeneca, Eli Lilly &amp; Company, Kowa, Novo Nordisk, Boehringer Ingelheim, Esperion, Cargene, Resverlogix, Novartis Pharmaceuticals, Silence Therapeutics, New Amsterdam, SCRIBE, CRISPR, VAXXINITY, CSL Behring, Bayer, Inc., Biologixpharma, Amarin. Grant Recipient; Self; Amgen Inc, Sanofi, Regeron, Merck, Pfizer, Inc. W. Sasiela: Consulting Fee; Self; Esperion. Employee; Self; Esperion. Stock Owner; Self; Esperion. T. Haddad: None. S. Nicholls: Consulting Fee; Self; Amgen Inc, Akcea Therapeutics, AstraZeneca, Boehringer Ingelheim, CSL Behring, Eli Lilly &amp; Company, Esperion, Kowa, Merck, Takeda, Pfizer, Inc., Sanofi-Regeneron, Novo Nordisk. Grant Recipient; Self; AstraZeneca, Amgen Inc, Anthera, CSL Behring, Cerenis, Eli Lilly &amp; Company, Esperion, Resverlogix, Novartis Pharmaceuticals, InfraReDx, Sanofi-Regeneron. N. Li: Employee; Self; Esperion. L. Cho: Consulting Fee; Self; Merck, AstraZeneca. Grant Recipient; Self; AstraZeneca, Novartis Pharmaceuticals. D. Mason: None. P. Libby: Advisory Board Member; Self; Amgen Inc, Caristo Diagnostics, Cartesian Therapeutics, CSL Behring, DalCor Pharmaceuticals, Dewpoint Therapeutics, Eulicid Bioimaging, Kancera, Kowa Pharamceuticals, Olatec Therapeutics, Medimmune, Novartis Pharmaceuticals, PlaqueTec, TenSixteen Bio, Soley Therapeutics, XBiotech, Inc. Grant Recipient; Self; Novartis Pharmaceuticals, Novo Nordisk, Genentech, Inc. S. Nissen: Grant Recipient; Self; Abbvie, AstraZeneca, Amgen Inc, Bristol-Myers Squibb, Eli Lilly &amp; Company, Esperion, Medtronic, MyoKardia, New Amsterdam Pharmaceuticals, Novartis Pharmaceuticals, Pfizer, Inc., Silence Therapeutics. Background: Statins are the foundation of treatment for atherosclerotic cardiovascular (CV) disease. The Cholesterol Treatment Trialists’ (CTT) Collaboration calculated in their meta-analyses of statin trials that every 1 mmol/L (39 mg/dL) reduction in LDL-C was associated with a 22% reduction in major vascular events (MVE), a benefit which increased with cumulative duration of therapy. In the CLEAR Outcomes trial, treatment of statin-intolerant pts with the ATP citrate lyase inhibitor bempedoic acid (BA) was associated with a 21% decrease in LDL-C compared with placebo and a 13% relative reduction in the risk of major adverse CV events (MACE) [hazard ratio (HR) 0.87, 95% CI 0.79-0.96. p=0.004]. It is unknown whether the relationship between LDL-C reduction and magnitude of CV benefits achieved with non-statin therapies such as BA differs from statins. Methods: The CLEAR Outcomes trial enrolled 13,970 pts with or at high risk for CV disease, 46% of whom had diabetes and 42% pre-diabetes, and with a baseline mean LDL-C of 3.60 mmol/L. We applied the CTT methodology and endpoint definitions to CLEAR Outcomes to derive normalized HRs associated with BA treatment for the composite MVE endpoint (fatal coronary heart disease, non-fatal MI, stroke, or revascularization) and individual CV outcomes per 1 mmol/L LDL-C reduction at 1 year. We assessed treatment effect of BA on CV events relative to LDL-C reduction in the Intention to Treat (ITT) population (all randomized pts) and in an on-treatment Per Protocol Set (PPS) population (censoring events occurring &amp;gt;30 days after early study drug discontinuation, which occurred in 29% and 32% of pts allocated to BA and placebo, respectively). Cumulative HRs were calculated per year of treatment duration. Results: In the ITT analysis, placebo-corrected absolute LDL-C reduction by BA at month 12 was 0.58 mmol/L with a HR (95% CI) for MVE of 0.85 (0.77, 0.94). In the PPS analysis, LDL-C reduction was 0.71 mmol/L with a HR for MVE of 0.80 (0.71, 0.89). When normalized to 1.0 mmol/L LDL-C reduction, HRs for ITT and PPS were 0.75 (0.63, 0.90) and 0.73 (0.62, 0.85), respectively and were comparable to normalized risk reduction with statins observed in the CTT meta-analyses [risk ratio (RR) 0.78, 95% CI 0.76, 0.80]. The cumulative normalized HR for MVE improved from 0.77 at year 1 to 0.72 by year 4 of BA treatment. Normalized HRs for individual endpoints of major coronary events, non-fatal MI, revascularization, and stroke for BA vs placebo in CLEAR Outcomes were comparable to the RRs for those endpoints with statins in the CTT meta-analyses. Conclusions: CV benefits achieved with BA are comparable to those obtained with statins, being proportional to the magnitude of absolute reductions in LDL-C, and increase over time. Use of and adherence to BA can provide substantial reductions in CV risk, in particular for those pts at high CV risk due to statin intolerance and high baseline LDL-C. Presentation: Thursday, June 15, 2023

SAT660 Predictors Of Achieving Body Weight Reduction ≥20% With Tirzepatide In People With Overweight Or Obesity In SURMOUNT-1

Abstract Disclosure: R. Srinath: Grant Recipient; Self; Dexcom. S. Pedersen: Other; Self; AstraZeneca, Bausch, Eli Lilly &amp; Company, Novo Nordisk, Jansen Pharmaceuticals, Boehringer Ingelheim, Sanofi, Merck, Abbott Laboratories, HLS, Bayer, Inc., Pfizer, Inc., Dexcom. L. Neff: Employee; Self; Eli Lilly &amp; Company. D. Cao: Employee; Self; Eli Lilly &amp; Company. C.Y. Kao: Employee; Self; Eli Lilly &amp; Company. A. Stefanski: Employee; Self; Eli Lilly &amp; Company. N. Ahmad: Employee; Self; Eli Lilly &amp; Company. C.J. Lee: Employee; Self; Eli Lilly &amp; Company. Background: Obesity is a chronic progressive disease affecting a growing number of adults and associated with many related complications. Next-generation anti-obesity medications (AOM) help achieve substantial body weight (BW) reduction needed to delay or prevent obesity-related complications. BW reduction of 20% or greater, once considered possible only with bariatric surgery, is now an achievable goal with next-generation AOMs. Tirzepatide, a GIP/GLP-1 receptor agonist approved for T2D and in development for chronic weight management, resulted in mean BW reduction of 15 - 21% in the Phase 3 SURMOUNT-1 double-blind, randomized, controlled trial. In this analysis we aimed to investigate predictors of achieving BW reduction ≥20 % with tirzepatide treatment in this trial. Methods: Adults with overweight or obesity who were randomized to receive once-weekly, subcutaneous (SC) tirzepatide (5 mg, 10 mg, or 15 mg) for 72 weeks and adherent to tirzepatide (≥75% doses received) were included in this analysis. Descriptive statistics were calculated for baseline values. Univariate logistic regression was performed on baseline demographics and laboratory values. Variables identified through a stepwise logistic regression were further analysed using a multivariate logistic regression model. Results: Among 1834 participants included in this analysis, 951 (52%) participants achieved 20% or greater BW reduction at week 72. Baseline factors associated with significantly higher odds of achieving BW reduction of ≥20% were female sex (OR [95% CI], p-value) (2.38 [1.90, 2.98], &amp;lt;0.001), lower baseline serum alanine aminotransferase (ALT) levels (1.17 [1.05, 1.30], 0.005), lower baseline HbA1c levels (1.62 [1.24, 2.10), &amp;lt;0.001), and no diagnosed hypertension (1.35 [1.09, 1.68], 0.005) based on multivariate analysis. Baseline factors not associated with higher odds of achieving BW reduction ≥20% were age, race, BW, years of education, fasting insulin, and systolic blood pressure. Conclusions: Approximately half of participants with obesity or overweight, without diabetes, treated with tirzepatide achieved BW reduction of 20% or greater in the SURMOUNT-1 study. Factors associated with a higher likelihood of achieving BW reduction of 20% or greater were female sex, lower ALT, lower HbA1c and no diagnosed hypertension at baseline. These findings may help guide obesity treatment goals and expectations with tirzepatide treatment, which is under investigation for chronic weight management. Presentation: Saturday, June 17, 2023

SAT134 CGM Use During Pregnancy Complicated By CF-Induced Diabetes

Abstract Disclosure: A.Y. Mazori: None. E.S. Markovic: None. C.J. Levy: Advisory Board Member; Self; Dexcom, Eli Lilly &amp; Company. Research Investigator; Self; Abbott Laboratories, Insulet Corporation, Tandem Diabetes Care, Dexcom. Introduction: Glycemic control remains challenging in pregnancies complicated by diabetes mellitus. Strict glycemic targets are required to optimize maternal and neonatal outcomes, but euglycemia is hindered by fluctuating insulin sensitivity and the need for frequent blood-glucose monitoring (BGM). Consensus guidelines recommend therapeutic continuous glucose monitoring (CGM) for pregnant and nonpregnant individuals with type 1 and type 2 diabetes, but current data support therapeutic CGM use in cystic fibrosis (CF)-related diabetes (CFRD) only outside of pregnancy. We report the case of a patient with CFRD who achieved recommended glycemic targets with a therapeutic CGM during a singleton pregnancy. Methods: A case report and literature review are presented. Results: A 32-year-old nulliparous woman with CF became pregnant via frozen-embryo transfer. Prior CF complications included CFRD, pancreatic insufficiency, and recurrent pancreatitis. A therapeutic Dexcom G6 CGM and intermittent BGM were used to monitor glycemic control before and during pregnancy; sensor use exceeded 96%. Pressure-induced sensor attenuations yielded sporadic hypoglycemic values discordant with simultaneous BGM. CGM analysis for the 90 days preceding conception revealed: time in range of 63-140 mg/dL (TIR) was 90.8%, time above range (TAR) 6.3%, and time below range (TBR) 2.9%. Throughout pregnancy, TIR was 92.9%, TAR 3.4%, and TBR 3.6%; no severe hypoglycemia occurred. Daytime (6AM to midnight) and nighttime hypoglycemia were 4.6% and 2.2%, respectively. In the first trimester, TIR was 90.8%, TAR 3.7%, and TBR 5.5%. During the second trimester, the patient achieved TIR 94.2%, TAR 2.6%, and TBR 3.2%. In the third trimester, TIR was 95.7%, TAR 0.9%, and TBR 3.4%. The pregestational CFRD regimen consisted of insulin glargine 12 units and lispro 3-8 units. The basal-insulin dose was 10 units at 13 weeks’ gestation, 9 units at 27 weeks’ gestation, and 8 units at 38 weeks’ gestation. The prandial-insulin doses varied between 1.5-5 units at 13 weeks’ gestation, 0-7 units at 27 weeks’ gestation, and 0-5 units at 38 weeks’ gestation. After an uncomplicated vaginal delivery at 38 weeks and six days’ gestation, maternal fasting hypoglycemia occurred after one dose of glargine 3 units. Euglycemia was obtained without basal, prandial, or correctional insulin. The neonate experienced mild hypoglycemia that resolved with oral glucose gel and feeding. The neonate was neither macrosomic nor large for gestational age (birth weight, 3.54 kg, 71st percentile) and did not require intensive-care unit management. Both the patient and neonate were discharged on postpartum day two. Conclusion: Therapeutic CGM use in a pregnancy complicated by CFRD was effective for maternal and neonatal outcomes. Further study is warranted to examine CGM use and efficacy in this population. Presentation: Saturday, June 17, 2023

SAT533 The Case of an Ectopic Thyroid Twin

Abstract Disclosure: A. Abu Limon: None. S.A. Aldasouqi: Consulting Fee; Self; Abbott Laboratories. P. Kachhadia: None. S. Khan: None. Introduction: Ectopic thyroid tissue is a rare but known developmental abnormality during the descent of the thyroid tissue from the floor of the foregut to its final location Infront of the trachea. The most frequent ectopic locations are the base of the tongue and anywhere along the course of the thyroglossal duct. It is very rare to have an ectopic thyroid tissue located in the mediastinum. It’s even more rare when the patient still has an almost normal thyroid gland in its usual location in the neck, and both are sizable and functional. Case Presentation: We are reporting the case of a 38-Year-old African American Female, who was involved in a car accident with non-critical injuries to her neck and chest area. She underwent a contrasted CT scan of her neck and chest that showed an anterior mediastinal mass towards the right at the level of the great vessels and arch, right paratracheal location overall measuring 6.0 x 4.6 x 4.5 cm. She was seen by Cardiothoracic surgery group and underwent Mediastinoscopy that confirmed a large firm to hard mass just inferior to the innominate artery was firmly adherent to the trachea as well as surrounding structures. Multiple biopsies showed thyroid tissue with focal mild chronic inflammation, benign. No atypia or malignancy is noted. Then, she was referred to our clinic for further evaluation. When interviewed, the patient denies any compressive symptoms (Shortness of breath, palpitations, chest pain or dysphagia). The patient has no personal or family history of thyroid disorders, including no thyroid cancer history. She has no Goiter on exam and no Pemberton sign is elicited. Laboratory work up was unremarkable including normal thyroid functions. Neck Ultrasound confirmed presence of a thyroid gland in its expected location, with Right Lobe Measurement: 5.04 x 1.70 x 1.47 cm Vol: 6.02 ml and Left Lobe Measurement: 3.94 x 1.25 x 1.21 cm Vol: 2.87 ml. We were keen to explore this matter further and ordered a thyroid uptake scan with 0.97 uCi iodine-123, that showed a 24-hour normal uptake of 27.4% at the thyroid bed and a separate substernal and RT paratracheal location uptake. Discussion: This patient has supplementary ectopic thyroid tissue in her mediastinum along with a normal thyroid gland in her neck. From the literature review and search, This is a very rare occurrence. The discussion with the patient is about the specific concern of the malignant potential of this ectopic thyroid and if surgical intervention is needed. The probability of cancer on ectopic thyroid tissue is less than 1% and when it occurs papillary carcinoma is the most common histology. Our patient has benign biopsy results and no signs nor symptoms related to this ectopic thyroid gland. The final decision is to not undergo surgery, but rather, a follow up with CT scan in 6 months. Presentation Date: Saturday, June 17, 2023

OR23-05 Log-term Efficacy And Safety Of Transcon PTH In Adults With Hypoparathyroidism: 52-week Results From The Open-label Extension Of The Phase 3 Pathway Trial

OR23-05 Log-term Efficacy And Safety Of Transcon PTH In Adults With Hypoparathyroidism: 52-week Results From The Open-label Extension Of The Phase 3 Pathway Trial

THU296 Effect Of Tirzepatide In GADA-positive Individuals With T2D: A Post Hoc Analysis Of The SURPASS 2-5 Trials

Abstract Disclosure: A.L. Peters: Advisory Board Member; Self; Abbott Diabetes Care, Eli Lilly &amp; Company, Medscape, Novo Nordisk, Zealand. Grant Recipient; Self; Dexcom, Insulet Corporation. Stock Owner; Self; Omada Health, Teladoc. Other; Self; Abbott Diabetes Care. R. Buzzetti: Consulting Fee; Self; Sanofi, Novo Nordisk, Eli Lilly &amp; Company. Speaker; Self; AstraZeneca, Abbott Laboratories. C.J. Lee: Employee; Self; Eli Lilly &amp; Company. Stock Owner; Self; Eli Lilly &amp; Company. I. Pavo: Employee; Self; Eli Lilly &amp; Company. Stock Owner; Self; Eli Lilly &amp; Company. M. Liu: Other; Self; Eli Lilly &amp; Company. J.S. Paik: Employee; Self; Eli Lilly &amp; Company. Stock Owner; Self; Eli Lilly &amp; Company. Tirzepatide, a novel once weekly GIP and GLP-1 receptor agonist, is approved for treatment of type 2 diabetes (T2D). People with T2D and positive glutamic acid decarboxylase autoantibodies (GADA), which is also referred to as latent autoimmune diabetes in adults (LADA), may often remain undetected and may be associated with more rapid progression to insulin therapy. The diagnosis is primarily made by the presence of GADA in patients previously diagnosed with T2D. The aim of this post hoc analysis was to evaluate the effect of tirzepatide on hemoglobin A1c (HbA1c) levels in people with T2D who were GADA-positive versus GADA-negative from the Phase 3 SURPASS clinical trial program. Tirzepatide-treated patients from SURPASS 2-5 studies were included in this analysis. Patients who had GADA concentrations ≥5 IU/mL were categorized as GADA-positive (ELISA, RSR Ltd., Cardiff, UK). Change from baseline in HbA1c at 40/42 weeks was assessed in GADA-positive vs GADA-negative patients using mixed model repeated measures from the efficacy analysis set, adjusting for baseline covariates including study, sex, HbA1c, and body mass index (BMI). All randomized patients who took at least one dose of study drug, excluding patients who discontinued study drug due to inadvertent enrollment and excluding data after initiation of rescue medication or premature discontinuation of study drug, were included in this analysis. Of the 3827 tirzepatide-treated patients who were tested for GADA, 3671 (95.9%) were GADA-negative, 120 (3.2%) were GADA-positive, and 36 (0.9%) were “no GADA status”. Baseline parameters were similar between the groups, except for baseline BMI and serum triglyceride concentration which were slightly lower in GADA-positive patients compared to GADA-negative patients (mean baseline BMI [SD] 32.2 [6.1] vs 33.6 [6.3] kg/m2, mean triglycerides 169.2 [101.3] vs 188.1 [131.4] mg/dL). At 40/42 weeks, both groups achieved significant reductions in HbA1c (-2.11% vs -2.32%; p&amp;lt;0.001 for both groups) and body weight (-9.2 kg vs -9.6 kg; p&amp;lt;0.001 for both groups), for GADA-positive vs. GADA-negative patients, respectively. Reductions in HbA1c were slightly greater in GADA-negative patients (estimated treatment differences [95% confidence interval]: 0.21% [0.03, 0.39]; p=0.024), whereas reductions in body weight did not significantly differ between groups (0.38 kg [-0.99, 1.75]; p=0.588). These data demonstrate that tirzepatide was effective in reducing HbA1c and body weight, irrespective of GADA status in adults with T2D, thus suggesting that tirzepatide may be effective to improve glycemic control in GADA-positive individuals. Future studies could help elucidate the long-term impact of GADA positivity on the progression of diabetes. Presentation: Thursday, June 15, 2023

Association between exposure to air pollution and blood lipids in the general population of Spain.

We aimed to assess the associations of exposure to air pollutants and standard and advanced lipoprotein measures, in a nationwide sample representative of the adult population of Spain. We included 4647 adults (>18 years), participants in the national, cross-sectional, population-based di@bet.es study, conducted in 2008-2010. Standard lipid measurements were analysed on an Architect C8000 Analyzer (Abbott Laboratories SA). Lipoprotein analysis was made by an advanced 1 H-NMR lipoprotein test (Liposcale®). Participants were assigned air pollution concentrations for particulate matter <10 μm (PM10 ), <2.5 μm (PM2.5 ) and nitrogen dioxide (NO2 ), corresponding to the health examination year, obtained by modelling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). In multivariate linear regression models, each IQR increase in PM10 , PM2.5 and NO2 was associated with 3.3%, 3.3% and 3% lower levels of HDL-c and 1.3%, 1.4% and 1.1% lower HDL particle (HDL-p) concentrations (p < .001 for all associations). In multivariate logistic regression, there was a significant association between PM10 , PM2.5 and NO2 concentrations and the odds of presenting low HDL-c (<40 mg/dL), low HDL-p (<p25) and higher LDL particle (LDL-p) concentrations (≥p75). In subgroup analyses there were stronger associations between PM10 and NO2 and low HDL-p in men (p for interaction .008 and .034), and between NO2 and low HDL-p in individuals with obesity (p for interaction .015). Our study shows an association between the exposure to air pollutants and blood lipids in the general population of Spain, suggesting a link to atherosclerosis.

A-093 Clinical Performance of Biomarkers for Traumatic Brain Injury

Abstract Background An estimated 5 million people are evaluated in emergency departments (ED) for Traumatic Brain Injury (TBI) in the United States each year. The vast majority (80%) of patients evaluated for TBI in the ED will receive head CT scans, however less than 10% of those will have any findings of acute traumatic abnormalities. This highlights the need for objective, rapid, accurate tools to help clinicians evaluate and triage TBI patients and reduce unnecessary radiation exposure. The Alinity i TBI test is a panel of in vitro diagnostic chemiluminescent microparticle immunoassays used to measure glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) in human plasma and serum. TBI performance was evaluated in a multi-center study by performing reproducibility and a pivotal study. Methods A pivotal study using prospectively collected archived (frozen) plasma specimens was conducted to establish the clinical performance of the TBI test on the Alinity i system. The testing of the archived specimens was performed at three clinical sites in the United States. The specimens tested were originally collected in a prospective, multi-center clinical study and were from individuals 18 years of age or older who presented to a health care facility or emergency department with suspected traumatic brain injury. These subjects had an initial Glasgow Coma Scale (GCS) score of 13–15 and had a computed tomography (CT) scan of the head performed per the clinical site’s standard of care. Reproducibility was assessed using multiple panel/control members for 5 days based on guidance from Clinical and Laboratory Standards Institute EP05-A3. Testing was conducted using 3 lots of GFAP and UCH-L1 reagents, and 1 Alinity i system at each of 3 testing sites. Results Of the 1899 mild TBI subjects, 120 had positive head CT scan results; 116 of the 120 specimens had a positive TBI interpretation (Sensitivity 96.7%;95%CI:91.7%,98.7%). Of the 1779 subjects with negative CT scan results, 713 had a negative TBI interpretation (Specificity 40.1%;95%CI:37.8%,42.4%). The negative predictive value (NPV) of the test was 99.4% (713/717, 95%CI:98.6%,99.8%). Within-Laboratory imprecision (includes repeatability, between-run, and between-day variance components) results ranged from 2.2% to 3.5% CV for GFAP and 1.8 to 3.2 %CV for UCH-L1. The Overall Reproducibility (includes repeatability, between-run, between-day, between-lot, between-site, and site-lot interaction variance components) results ranged from 2.5% to 4.7% CV for GFAP and 2.6 to 6.6 %CV for UCH-L1. Conclusion The Alinity i TBI clinical performance results demonstrated that the TBI test is characterized by high sensitivity and high NPV, which supports the clinical utility to assist in determining the need for a CT scan of the head in subjects presenting with suspected mild TBI. The GFAP and UCH-L1 assays demonstrated acceptable reproducibility across a wide dynamic range. These assays can report results within 18 min and be conveniently loaded into the Electronic Health Records to aid clinicians in their triage (or imaging) decisions. Funding The study was funded by Abbott Laboratories and in collaboration with the US Army Medical Materiel Development Activity, US Army Medical Research and Development Command CRADA 20-1266-CRA.

B-303 Comparison of Tacrolimus Concentrations Obtained By the Newly Approved Alinity i Tacrolimus Assay With a Reference Liquid-Chromatography Combined With Tandem Mass spectrometry Assay

Abstract Background Tacrolimus belongs to the calcineurin-inhibitor class of medications and used for preventing and maintenance of organ rejection in transplant recipients alone or in combination with other medications. Due to narrow therapeutic window and significant nephrotoxicity, this drug is routinely monitored with a suggested therapeutic range of 5–15 ng/mL. Recently, Abbott Laboratories (Abbott Park, IL) received FDA approval for using tacrolimus immunoassay on the Alinity i platform. We compared tacrolimus values in 101 transplant patients using Alinity i analyzer and a reference method based on liquid chromatography combined with mass tandem spectrometry (LC-MS/MS). Methods Tacrolimus immunoassay on the Alinity i analyzer is a chemiluminescent microparticle immunoassay (CMIA) requiring pretreatment of whole blood specimen prior to analysis. The analytical measurement range of the assay is 2–30 ng/mL. The left-over blood specimens were sent to Eurofins-Viracor reference laboratory in Lenexa, KS for analysis using LC-MS/MS method. After liquid-liquid extraction, specimens were analyzed using ascomycin as the internal standard for the presence of tacrolimus (assay is capable of analyzing other immunosuppressants simultaneously). UPLC C-18 column (waters) was used for separation using two mobile phases (A: 2.0 mM ammonium acetate in 0.1% formic caid in water and B: 2.0 mM ammonium acetate in 0.1% formic acid in methanol). Mass spectrometer was operated in positive ionization electrospray mode (tacrolimus m/z 821.6 &amp;gt; 768.6, ascomycin m/z 809.756.6. Results The total precision of the low control was 3.6% (mean: 4.48 ng/mL; CV 0.16 ng/mL, n = 20) while the total precision of the high control was 5.1% (mean: 25.4 ng/mL, SD: 1.29 ng/mL, n = 20). The linearity of the assay (2.0–30.0 ng/mL) was verified by running various calibrators as unknown. Comparing tacrolimus values in specimens from 101 transplant patients (49 kidney, 19 bone marrow transplant, 16 liver and 15 heart transplant) using the reference method (LC-MS/MS) as the x-axis and the corresponding values obtained by the tacrolimus immunoassay using Alinity I analyzer, we observed the following regression equation: y = 0.97 x + 1.005 (n = 101, r = 0.95). For kidney transplant recipients, the regression equation was y = 0.96 + 1.20 (n = 49, r = 0.94). Discussion Excellent correlation between tacrolimus values obtained by the newly FDA approved tacrolimus immunoassay with the reference LC-MS/MS based assay indicates further improvement in the performance of immunoassays for therapeutic drug monitoring of immunosuppressants. This may be due to reduced cross-reactivity of metabolites as indicated in the package insert. Conclusions The newly approved tacrolimus immunoassay for the application on the Alinity I analyzer can be used for routine therapeutic drug monitoring of tacrolimus in clinical laboratories.

A-369 Evaluation of a Point-of-Care Whole Blood Creatinine Assay and eGFR Concordance using the CKD-EPI 2021 Equation

Abstract Background Estimated glomerular filtration rate (eGFR) from serum creatinine is considered a better assessment of renal function than serum creatinine alone. Patients with chronic kidney disease have a higher risk of developing contrast-induced nephropathy (CIN). GEM Premier ChemSTAT (Instrumentation Laboratory, Bedford, USA) whole blood (WB) creatinine assay along with eGFR reporting capability per the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 eGFR equation is now available and could provide a quick point-of-care (POC) screening test alternative to the lab assay for patient risk management. Currently the CKD-EPI 2009 formula for non-AA population has been used to estimate eGFR in our institution. Recently the CKD-EPI 2021 equation without race adjustment has been recommended by multiple professional societies. The goal of this clinical evaluation was to compare the analytical performance of the ChemSTAT WB creatinine assay and the clinical concordance of eGFR to an established lab method by CKD-EPI 2021 equation. Methods Remnant heparinized WB samples along with age and gender were obtained. The WB samples were analyzed on the GEM Premier ChemSTAT and the plasma assayed on an Architect analyzer (Abbott Laboratories, Lake Forest, USA) as the reference method. The eGFR based on the CKD-EPI 2009 equation were obtained for both WB and plasma creatinine. The eGFR based on CKD-EPI 2021 equation were retrospectively calculated based on WB and plasma creatinine, age and gender. The clinical concordance of categorizing patients with abnormal kidney function (eGFR &amp;lt; 60 ml/min/1.73 m2) and overall concordance of patients (eGFR &amp;lt; 60 + eGFR≥60) was assessed for WB vs plasma eGFR. Error grid analysis was performed for eGFR as described by Snaith et al. (1) to identify the impact of discordant results between WB and plasma eGFRs. Results A total of 60 patient samples were analyzed, median age (SD) = 68.5 (15.2), 53.3% female. The WB ChemSTAT creatinine assay correlated well with the Architect across the tested ranges with regression results of: ChemSTAT_Creatinine (μmol/L) = 1.1099*Architect_Creatinine – 16.0, r = 0.990. A small mean bias (SD) of -3.0 (22.6) μmol/L was observed between ChemSTAT and Architect from the Bland-Altman analysis. When identifying patients with abnormal kidney function (eGFR &amp;lt; 60), ChemSTAT WB eGFR showed 84% (21/25) concordance against the plasma eGFR. An overall clinical eGFR concordance of 88% (53/60) was observed for ChemSTAT. The error grid analysis indicated 100% (60/60) of ChemSTAT WB eGFRs (Zones A and B combined) had no implication to clinical management. Mean biases (SD) from reported CKD-EPI eGFR 2021 vs 2009 equation of 3 (1.6) and 2 (2.6) were observed from Architect plasma creatinine and ChemSTAT WB creatinine, respectively. Conclusions Strong correlations were observed between the ChemSTAT WB POC creatinine assay and eGFR versus the lab method. Based on the high clinical concordance of WB eGFR with CKD-EPI 2021 equation and low mean bias, GEM Premier ChemSTAT demonstrated good performance as POC method for rapid and lab quality renal function assessment.

B-187 Evaluation of Clinical Utility of LC-MS/MS Method for Thyroglobulin Measurement in Comparison with Immunoradiometric Assay and Chemiluminescence Microparticle Immunoassay

Abstract Background Thyroglobulin (Tg) is the follow-up index of choice for patients with differentiated thyroid cancer (DTC), especially who were undergone total thyroidectomy. However, due to the commonly used immunoassay’s inherent susceptibility to interference combined with the high prevalence of thyroglobulin antibody (TgAb) in DTC patients, the need for more reliable measurement for Tg independent from TgAb has been brought up. In this study, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for Tg measurement and compared its clinical usefulness and analytical performance with immunoradiometric assay (IRMA) and chemiluminescence microparticle immunoassay (CMIA). Methods We developed trypsin digestion-peptide immunoaffinity LC-MS/MS methods for Tg measurement. Analysis was performed using an LC-MS/MS system consisting of Agilent 1290 LC (Agilent Technologies, Santa Clara, CA) and Qtrap 5500+ MS/MS system(ABSciex, Framingham, MA). Tryptic Tg specific peptide (FSPDDSAGASALLR) and cleavable internal standard peptide (LSFYWTTTGDPFFDSHSDSLL*RSGPYMPQ, L*: 13C6, 15N) were quantitated against 5-point linear calibration curve with Access Thyroglobulin Calibrators (Beckman Coulter, Pasadena, CA). Three levels of serum control were prepared (3.95, 12.5, and 39.4 ng/mL). Lower limit of quantitation (LLoQ), linearity, precision, and carryover were validated for the assay. For method comparison, serum from patients with DTC or Hashimoto thyroiditis was collected. Tg was also measured with IRMA using BRAHMS TG Plus (Thermo Fisher Scientific, Waltham, MA), and CMIA using Architect Thyroglobulin (Abbott laboratories, Illinois, CA). TgAb was measured with IRMA using BRAMS Anti-Tg (Thermo Fisher Scientific) and the cut-off for TgAb was 60 IU/mL. Also, interference of TgAb was evaluated by comparing the Tg recovery of five sets of TgAb negative samples spiked with diluents and high TgAb samples. Results Within-run and between-run imprecisions were CV 7.8%–13.0% and CV 8.9%–12.7%, respectively. LLoQ was 0.5 ng/mL. The assay was linear through 0.5–650 ng/mL. No significant carryover was observed within the analytical measurement range. Out of the total 193 samples, the number of samples above LLoQ in both LC-MS/MS, and IRMA or CMIA were 73 samples (45 TgAb-positive and 28 TgAb-negative samples) and 69 samples (42 TgAb-positive and 27 TgAb-negative samples), respectively. The result well correlated between LC-MS/MS and IRMA (R2 = 0.99), and LC-MS/MS and CMIA (R2 = 0.98) in overall samples. When analyzed according to TgAb status, LC-MS/MS and IRMA (R2 = 0.84), and LC-MS/MS and CMIA (R2 = 0.93) correlated rather poorly in TgAb-positive samples, while TgAb-negative samples were consistent (R2 = 0.99 for IRMA, R2 = 0.97 for CMIA). We found one case with systemic metastatic thyroid cancer that showed significantly high Tg levels in IRMA and LC-MS/MS (above the upper limit of quantitation), whereas below LLoQ in CMIA. The interference of TgAb was negligible in LC-MS/MS, while significant interference was observed in CMIA, with a mean recovery rate of 57.6% (4.3%–82.5%). In one sample, when measured with CMIA, thyroglobulin level was 3.29 ng/mL when mixed with diluent, but below LLoQ (0.14 ng/mL) when spiked with TgAb-positive samples (TgAb 1700 IU/mL). Conclusion The LC-MS/MS method for Tg measurement was less prone to antibody interference than immunoassays. Measurement of Tg using LC-MS/MS would be useful for reliable diagnosis and proper management in TgAb-positive patients.

The Quality of MitraClip™ Content on YouTube.

Objective YouTube (YouTube LLC,San Bruno, California, United States) is used as a primary resource for many patients looking to gain healthcare knowledge. Recently, YouTube made efforts to increase the quality of posted content by accrediting trusted healthcare sources. With an increasing emphasis being placed on minimally invasive options, this study was done to investigate the quality of YouTube videos on MitraClip™ (Abbott Laboratories,Chicago, Illinois, United States) with respect to patient education. Methods YouTube was searched using the keyword "MitraClip". A total of 66 videos were evaluated, with 32 of those videos being included for final analysis after applying exclusionary criteria. Three independent reviewers separately scored the videos using the Global Quality Scale. Likes, dislikes, views, comments, and dates of upload were also recorded. Two-tailed t-tests were used to determine statistical significance. Results MitraClip videos on YouTube proved to be of medium quality, receiving an average Global Quality Scale score of 3.39. When stratified by the new YouTube accreditation process, those with accreditation had a significantly higher Global Quality Scale score of 4.11, while non-accredited videos had an average Global Quality Scale score of 3.12 (p<0.01). Shorter and more patient-friendly videos were also significantly lower in quality (p<0.05). Conclusion The YouTube accreditation process has demonstrated initial success at regulating the quality of MitraClip content, thereby reducing the spread of misinformation. However, this progress is undermined by the lack of unique videos present on the platform. Increasing the amount of original content about MitraClip may allow viewers to diversify their educational sources and ultimately gain a better understanding of the procedure.

Implant-friendly MRI of deep brain stimulation electrodes at 7 T.

The purpose of this study is to present a strategy to calculate the implant-friendly (IF) excitation modes-which mitigate the RF heating at the contacts of deep brain stimulation (DBS) electrodes-of multichannel RF coils at 7 T. An induced RF current on an implantable electrode generates a scattered magnetic field whose left-handed circularly polarizing component ( ) is approximated using a -mapping technique and subsequently used as a gauge for the electrode's induced current. Using this approach, the relative induced currents resulting from each channel of a multichannel RF coil on the DBS electrode were calculated. The IF modes of the corresponding multichannel coil were determined by calculating the null space of the relative induced currents. The proposed strategy was tested and validated for unilateral and bilateral commercial DBS electrodes (directional lead; Infinity DBS system, Abbott Laboratories) placed inside a uniform phantom by performing heating and imaging studies on a 7T MRI scanner using a 16-channel transceive RF coil. Neither individual IF modes nor shim solutions obtained from IF modes induced significant temperature increase when used for a high-power turbo spin-echo sequence. In contrast, shimming with the scanner's toolbox (i.e., based on per-channel fields) resulted in a more than 2°C temperature increase for the same amount of input power. A strategy for calculating the IF modes of a multichannel RF coil is presented. This strategy was validated using a 16-channel RF coil at 7 T for unilateral and bilateral commercial DBS electrodes inside a uniform phantom.

Insertable Cardiac Monitoring Results in Higher Rates of Atrial Fibrillation Diagnosis and Oral Anticoagulation Prescription after Ischaemic Stroke.

After an ischaemic stroke, atrial fibrillation (AF) detection allows for improved secondary prevention strategies. This study aimed to compare AF detection and oral anticoagulant (OAC) initiation in patients with an insertable cardiac monitor (ICM) versus external cardiac monitor (ECM) after ischaemic stroke. Medicare Fee-for-Service (FFS) insurance claims and Abbott Labs device registration data were used to identify patients hospitalized with an ischaemic stroke in 2017-2019 who received an ICM or ECM within three months. Patients with continuous Medicare FFS insurance and prescription drug enrolment in the prior year were included. Patients with prior AF, atrial flutter, cardiac devices, or OAC were excluded. ICM and ECM patients were propensity score matched 1:4 on demographics, comorbidities, and stroke hospitalization characteristics. The outcomes of interest were AF detection and OAC initiation evaluated with Kaplan-Meier and Cox proportional hazard regression analyses. A total of 5,702 Medicare beneficiaries (ICM, n=444; ECM, n=5,258) met inclusion criteria. The matched cohort consisted of 2,210 Medicare beneficiaries (ICM, n=442; ECM, n=1,768) with 53% female, mean age 75 years, and mean CHA₂DS₂-VASc score 4.6 (1.6). ICM use was associated with a higher probability of AF detection (hazard ratio (HR) 2.88, 95% confidence interval (CI) [2.31, 3.59]) and OAC initiation (HR 2.91, CI [2.28, 3.72]) compared to patients monitored only with ECM. Patients with an ischaemic stroke monitored with an ICM were almost 3 times more likely to be diagnosed with AF and to be prescribed OAC compared to patients who received ECM only.

A Randomized, Controlled Trial of Efficacy and Safety of Cannabidiol in Idiopathic and Diabetic Gastroparesis

Cannabis (delta-9-tetrahydrocannabinol), a nonselective cannabinoid-receptor agonist, relieves nausea and pain. Cannabidiol (CBD), a cannabinoid receptor 2 inverse agonist with central effects, also reduces gut sensation and inflammation. We compared the effects of 4 weeks of treatment with pharmaceutical CBD vs placebo in patients with idiopathic or diabetic (diabetes mellitus) gastroparesis. We performed a randomized, double-blinded, placebo-controlled study of CBD twice daily (Epidiolex escalated to 20 mg/kg/d; Jazz Pharmaceuticals, Dublin, Ireland) in patients with nonsurgical gastroparesis with delayed gastric emptying of solids (GES). Symptoms were assessed by the Gastroparesis Cardinal Symptom Index Daily Diary. After 4 weeks of treatment, we measured GES, gastric volumes, and Ensure (Abbott Laboratories, Abbott Park, IL) satiation test (1 kcal/mL, 30 mL/min) to assess volume to comfortable fullness and maximum tolerance. Patients underwent specific FAAH and CNR1 genotyping. Statistical analysis compared 2 treatments using analysis of variance including baseline measurements and body mass index as covariates. Among 44 patients (32 idiopathic, 6 diabetes mellitus type 1, and 6 diabetes mellitus type 2), 5 patients did not tolerate full-dose escalation; 3 withdrew before completing 4 weeks of treatment (2 placebo, 1 CBD); 95% completed 4 weeks of treatment and diaries. Compared with placebo, CBD reduced the total Gastroparesis Cardinal Symptom Index score (P= .008), inability to finish a normal-sized meal (P= .029), number of vomiting episodes/24 hours (P= .006), and overall symptom severity (P= .034). Patients treated with CBD had a higher volume to comfortable fullness and maximum tolerance and slower GES. FAAH rs34420 genotype significantly impacted nutrient drink ingestion. The most common adverse events reported were diarrhea (14 patients), fatigue (8 patients), headache (8 patients), and nausea (7 patients). CBD provides symptom relief in patients with gastroparesis and improves the tolerance of liquid nutrient intake, despite slowing of GES. gov NCT #03941288.

Analysis of Determinants for Suture-mediated Closure Device Failure During EVAR Procedures.

Endovascular aortic repair (EVAR) for elective and emergency infrarenal aortic pathologies is the primary approach for treatment nowadays. During such procedure, the suture-mediated closure device (SMCD) (Perclose ProGlideTM, Abbott Laboratories, Chicago, IL, USA) is commonly used. This study aimed to identify potential contributors for SMCD failure in a patient cohort of elective and emergency EVAR. Archived medical records from patients who underwent EVAR for aortic pathologies in elective and emergency setting at the University Hospital Düsseldorf, Germany were included. Patient's co-morbidities, access vessel morphologies and hemostasis-related blood parameters were evaluated on their association with SMCD failure applying different statistical methods. A total of 71 patients (139 femoral accesses) was included. The mean age was 73.5 ± 8.4years. Overall SMCD failure rate was 4.3%, 4.1% for elective and 5.9% for emergency cases, respectively. Total procedure time was longer for the SMCD failure group (323 ± 117.8min vs 171 ± 43.7min). The calcification status of the common femoral artery (CFA), the diameter of the aortic bifurcation, and dual anti-platelet therapy (DAPT) on the medication plan prior to the procedure were associated with SMCD failure. Univariate binary logistic regression analysis nominated several potentially relevant predictors for SMCD failure who underwent subsequent multivariable binary logistic regression analysis. Here, DAPT on the medication plan was identified as being promising in predicting SMCD failure (OR 30.5), while anterior plaque formation in the CFA maintained as only statistically relevant determinant (OR 44.9). This study confirms the CFA calcification status to be associated with SMCD failure. Although discontinued prior to endovascular treatment, DAPT was also found to be associated with SMCD failure. Our results may advocate to perform obligatory platelet testing prior to EVAR to maximize patient safety.

Association between fractional flow reserve and CMR-derived exercise capacity

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NMRC Open-Fund Young Individual Research Grant, Singapore. NMRC Open-Fund Individual Research Grant, Singapore. Background In-scanner exercise stress cardiac magnetic resonance (ExCMR) imaging using supine cycling ergometer offers assessment of perfusion defects, inducible regional wall motion abnormalities, viability and exercise capacity in a single examination (EMPIRE Trial). Aim We aim to investigate the role of CMR-derived exercise capacity to assess the physiological stenosis severity, measured by invasive fractional flow reserve (FFR). Methods 107 patients (60±8 years, 80 males) with suspected coronary artery disease (CAD) underwent ExCMR (Siemens 1.5T) and invasive coronary angiogram with FFR measurement (PressureWireTMX Guidewire – Abbott Laboratories) followed previously published trial protocol [1]. Exercise capacity was derived as age- and sex-specific percentile of peak cardiac index, according to the reference range previously established [2]. Results Exercise capacity remains the only predictor of FFR values (beta 0.005, P&amp;lt;0.001) with backward multivariate regression of clinical variables (age, sex, BMI, presence of hyperlipidema, blood pressure, presence of diabetes mellitus) and quantitative CMR parameters (LV mass, extracellular volume, LV stroke volume at rest and exercise capacity). Patients with haemodynamically significant CAD (FFR&amp;lt;0.8) had significantly lower exercise capacity (median 14 [IQR 4–20] vs 5 [IQR 1–10] age- and sex-specific percentile of peak cardiac index, P&amp;lt;0.001) Conclusion In addition to perfusion defects, regional wall motion abnormalities and viability assessment to detect coronary artery disease, exercise capacity predicts the physiological stenosis severity.