tbuckley/cabot-search huggingface dataset:
Abstract 12298: A Sequential Deep Learning Approach for Automated Detection and Attribution of Coronary Artery Calcification in Non-Contrast CT
Authors: Ammar Hoori, Yingnan Song, Juhwan Lee, Sadeer Al-Kindi, Sanjay Rajagopalan, David Wilson
Journal: Circulation (2021)

Introduction: Coronary artery calcium (CAC) is strongly predictive of adverse cardiovascular events, and is widely utilized for risk stratification. There is considerable interest in automated machine learning techniques for analysis of coronary calcification, that may provide incremental prognostic value and personalization in CV care. Hypothesis: Deep-learning (DL) approaches provide accurate and time-efficient automated detection of individual calcifications and classification of their corresponding territory. Methods: Two automated deep learning (DL) techniques are proposed. We use a standard detection criterion (3 connected voxels &gt;130-HU). The first DL classifies “true” CAC from an extra-coronary calcification (NON-CAC). NON-CACs include bone, aortic calcifications, noise, and lung calcifications. Candidate calcifications are centered in 2D CT patches. Each patch contains three channels of the lesion with 3 scales (х0.5, original, х2), respectively. The second DL classifies CACs as belonging to coronary territories (LAD, LCX, and RCA) using CAC patches associated with their corresponding coronary territories. Results: We used a dataset of 66 patients that generates (1903/4745: CAC/NON-CAC) patches for the first DL, while the CAC patches are subdivided into (695/321/887: LAD/LCX/RCA) patches for the second DL. We trained, validated, and tested our first DL in 80%, 10%, and 10% of patches and the second DL with a 70%,10%, and 20% split respectively. ResNet50 DL outperformed other DL algorithms for both determinations of CAC and classification of territory. Our method provides a highly accurate solution for automated CAC detection with accuracy and precision of 98.8% and 97.9%, respectively. CAC arterial classification (artery-based) showed an accuracy of 99.5%, 99.7%, and 100% for LAD, LCX, and RCA, respectively. with a precision of 98.6%, 100%, 100%, respectively. Conclusions: In this preliminary study, an automated DL framework correctly identified coronary calcifications and their corresponding territories. Further studies are warranted to scale our approach to automate CAC analysis for precision medicine approaches.
Abstract 11678: Prevalence of Elevated Blood Pressure and Left Ventricular Hypertrophy in Adolescents With Congenital Heart Disease
Authors: Aaron T Walsh, Kan N Hor, Marc Lee, Simon Lee, Andrew H Tran
Journal: Circulation (2021)

Introduction: Left ventricular hypertrophy (LVH) is defined as LVM indexed to height 2.7 (LVMi-HT 2.7 ≥ 51 g/ht 2.7 in men, ≥ 47 g/ht 2.7 in women), and ≥ 38.6 g/ht 2.7 in the pediatric population. LVH associated with hypertension (HTN) is a predictor of adverse cardiovascular (CV) events in adulthood. Adults with congenital heart disease (CHD) have higher rates of HTN compared to the general adult population. Data on the prevalence of elevated systolic blood pressure (SBP) in youths with CHD is limited. The aim of our study was to determine the prevalence of elevated SBP and LVH in adolescents with CHD. Hypothesis: We hypothesized that youths with elevated SBP will have increased LVMi-HT 2.7 by echocardiography. Methods: We retrospectively analyzed echocardiograms with a diagnosis code of CHD from 2012 to 2019. We included patients aged 13-17 years with documented BP, height, weight, and echocardiography measurement for LVMi-HT 2.7 . Patients were grouped by BP category into normotensive (NT, SBP &lt; 120 mm Hg), elevated BP (E-BP, 120 ≤ SBP &lt; 130 mm Hg), Stage 1 HTN (HTN-1, 130 ≤ SBP &lt; 140 mm Hg), and Stage 2 HTN (HTN-2, SBP ≥ 140 mm Hg). The prevalence of LVH was reported in each group defined as LVMi-HT 2.7 ≥ 38.6 g/ht 2.7 . Results: 855 patients were included with a mean age of 15.5±1.5 years with 485/855 (56.7%) male, SBP 117±13.5 mm Hg, and LVMi-HT 2.7 34.2±10.5 g/ht 2.7 . 493/855 (57.7%) were in the NT group, 214/855 (25%) in E-BP, 99/855 (11.6%) in HTN-1, and 49/855 (5.7%) in HTN-2. The prevalence of LVH increased with higher SBP with 96/493 (19.5%) in NT, 80/214 (37.4%) in E-BP, 32/99 (32.3%) in HTN-1, and 20/49 (40.8%) in HTN-2. Of the youths with LVH, 49/228 (21.5%) met adult criteria of ≥ 51 g/ht 2.7 . Conclusions: Youths with CHD have a high prevalence of elevated BP, HTN, and LVH. These findings support the importance of early detection and screening for high BP in this group because youths with CHD have baseline increased CV risk that may be compounded by HTN. Future studies will be needed to determine longitudinal changes and the influence of body mass index and sex on BP in this group.
Abstract 6913: Measuring Cerebrovascular Reactivity in Moyamoya Disease: Insights from Simultaneous PET/MRI
Authors: Yize Y Zhao, Michael E Moseley, Gary Steinberg, Greg Zaharchuk
Journal: Circulation (2021)

Introduction: Cerebrovascular reactivity (CVR) reflects the change in cerebral blood flow (CBF) in response to a vasoactive stimulus. Studies have demonstrated that impaired CVR was associated with a higher risk of stroke. PET imaging with 15 O-water as the radiotracer has been the standard modality to measure CBF and CVR. But it is impractical in most hospitals due to the requirement of an on-site cyclotron. Arterial spin labeling is a quantitative MRI technique that enables non-invasive CBF and CVR measurement. Hypothesis: ASL with multiple delays was more accurate than with single delay, using 15 O-water PET as the reference. Methods: Data were collected from 26 Moyamoya patients (18-64 years, 16 females) using a simultaneous 3T PET/MRI system (GE SIGNA, Waukesha, WI, USA). All patients had unilateral or bilateral vessel occlusion at the anterior cerebral artery (ACA), middle cerebral artery (MCA), and/or posterior cerebral artery (PCA). Imaging data were acquired using single post-labeling delay pseudo-continuous ASL (single-PLD PCASL), delay pseudo-continuous ASL (multi-PLD PCASL, 3 PLDs), and 15 O-water PET simultaneously at baseline and 15 minutes after the injection of the vasodilator acetazolamide (15 mg/kg with a maximum of 1 g). CBF of PET was computed using the single-compartment pharmacokinetic model; CBF of ASL was computed using the general kinetic model. CVR was computed as the percentage of CBF change compared with baseline CBF. Paired t-tests were performed to compare the mean CVR between the affected and unaffected territories. Results: Our quantitative analysis showed that the CVR of the affected regions was significantly lower than the normal regions (by 68%, 52%, and 56% for PET, single-PLD PCASL, and multi-PLD PCASL respectively). Conclusions: Both single and multi-delay ASL were effective in detecting impaired CVR in Moyamoya patients.
Abstract 12843: Amyloidosis is Associated With Increased Risk of Atrial Fibrillation. A Forgotten Link Between Uncommon and Common Cardiac Conditions. Analysis From the National Inpatient Sample
Authors: Amr Salama, Abdullah Abdullah, Ahmed Hussein, David Corteville, Mohan Rao, Richard Alweis
Journal: Circulation (2021)

Objective: This study aims at identifying the relationship between amyloidosis and atrial fibrillation Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk of stroke, heart failure, and mortality. Recent advances in cardiac imaging have increased the frequency of diagnosis of cardiac amyloidosis. Data is limited on the role of cardiac amyloid in patients with AF. Methods: This is a retrospective cohort study of patients with amyloidosis from the National Inpatient Sample (NIS) 2014. The primary outcome was diagnosis of AF in the amyloidosis vs. non-amyloidosis population. Logistic regression models were used to assess predictors of AF among the study population. Results: 5, 872,587 health encounters from the NIS were identified. Of these, 4,287 subjects had a diagnosis of amyloidosis. AF was found in 28.7% of the amyloidosis vs. 13.4% % of the non-amyloidosis group, p &lt; 0.001. The average age of the amyloidosis is 71 yrs. old, female represents 55.9% of the study population. Systolic heart failure (8.5% vs. 3.9%, p &lt; 0.001), diastolic heart failure (14.7% vs. 4.6%, p &lt; 0.001), ischemic stroke (6.3% vs. 1.9%, p &lt; 0.001) and chronic kidney disease (42.3% vs. 14.4%, p &lt; 0.001) were more prevalent in the amyloidosis vs. non-amyloidosis group. Amyloidosis was associated with the black ethnicity (19.4% vs. 14.1%, p &lt; 0.001). In addition, diabetes mellitus, hypertension, and obesity were common in the amyloidosis group. On multivariate analysis, amyloidosis was a strong predictor of AF (OR 1.37 (95% CI 1.28-1.47, p &lt; 0.001)) Conclusion: AF and amyloidosis are mutually associated identities. High suspicion should be maintained for the diagnosis of amyloidosis in patients presenting with AF. This may allow early recognition and treatment of underlying amyloidosis in patients with AF.
Abstract 10372: A Clinical Drug-Drug Interaction Study of Imb-1018972, a Novel Investigational Cardiac Mitotrope in Phase 2 Development for the Treatment of Myocardial Ischemia and Hypertrophic Cardiomyopathy
Authors: Larry Tremaine, Suliman Al-Fayoumi, Jeroen van de Wetering, Thjis van Iersel, Jaikrishna Patel, Paul Chamberlin
Journal: Circulation (2021)

Background: IMB-1018972 (IMB-101) is a novel mitotropic agent designed to increase myocardial metabolic efficiency by shifting substrate utilization towards glucose through reducing fatty acid oxidation (inhibiting 3-ketoacyl CoA thiolase), thereby generating more ATP per unit of oxygen consumed. IMB-101 is hydrolyzed to IMB-1028814 (IMB-102, the active moiety) which is further metabolized with ~60% forming trimetazidine (TMZ). In vitro cytochrome P450 (CYP) studies reveal IMB-102 to be metabolized by multiple CYPs with CYP2C19 and CYP2D6 potentially comprising a major portion of its clearance and formation of TMZ. IMB-101 is under evaluation in Phase 2 studies in stable CAD, non-obstructive HCM &amp; T2DM, indications for which patients often take multiple medications concurrently. Aim: To evaluate the drug-drug interaction (DDI) potential of IMB-101 in healthy subjects. Methods: A fixed sequence crossover study conducted in 3 parts evaluating the effect of: 1) multiple dose oral (PO) IMB-101 on the single dose PK of PO CYP3A4 (midazolam) and CYP2C8 (repaglinide) substrates (n=23); multiple doses of strong inhibitors of 2) CYP2D6 (paroxetine) or 3) CYP2C19 (fluvoxamine) on the single dose PK of PO IMB-101 (n=14 each). Results: 1) Weak inhibition of CYP2C8 by IMB-101 based on AUC of repaglinide but none based on its Cmax. Weak inhibition of CYP3A4 by IMB-101 based on AUC and Cmax of midazolam. 2) Limited involvement of CYP2D6 in the metabolism of IMB-102 to metabolites other than TMZ based on IMB-102 AUC and Cmax when given with paroxetine. 3) A major role for CYP2C19 in the metabolism of IMB-102 to TMZ in vivo evidenced by increased IMB-102 exposure and reduced TMZ exposure when given with fluvoxamine. Based on the summation of AUCs for the active entities (IMB-102 and TMZ), exposure is unchanged with co-administration of fluvoxamine suggesting no IMB-101 dose adjustment is needed with concurrent strong CYP2C19 inhibition. Conclusions: IMB-101 does not result in clinically significant inhibition of CYP3A4 or 2C8 isoenzymes and its metabolites are not clinically relevant CYP2D6 substrates. These findings support the administration of IMB-101 with commonly used cardiovascular medications without a significant risk of DDI or requirement for dose alterations.
Abstract 10310: Deep Learning for a Diagnosis of Plaque Erosion in Patients with Acute Coronary Syndromes
Authors: Makoto Araki, Sangjoon Park, Akihiro Nakajima, Hang Lee, Jong Chul Ye, Ik-kyung Jang
Journal: Circulation (2021)

Background: The diagnosis of plaque erosion by optical coherence tomography (OCT) in patients with acute coronary syndromes (ACS) requires expertise in image interpretation. Objectives: This study sought to develop a deep learning (DL) algorithm that enables an accurate diagnosis of plaque erosion even for readers without experience in image interpretation. Methods: An image sequence transformer DL algorithm that mirrors the attention given by cardiologists to sequential images during a pull-back, was developed. The DL model was trained and internally validated for a diagnosis of plaque erosion both at the frame-level and at the patient-level in 581 ACS patients from 8 institutions in 4 countries. The model was externally tested in 292 ACS patients from an independent dataset. Training and validation dataset included 237,021 cross-sectional OCT images and testing dataset 65,394 cross-sectional OCT images. The OCT image classification performance was evaluated by area under the receiver-operating characteristic curve (AUC), and sensitivity and specificity. The results were compared against diagnoses made by OCT experts both at the frame-level and at the patient-level. Results: In the training and validation data set, 206 (43.2%) patients had plaque erosion, while in the external testing data set, 86 (29.5%) patients had plaque erosion. In the external testing data set, the DL model diagnosed plaque erosion with an AUC of 0.963 (95% CI, 0.962-0.963), a sensitivity of 89.9% (95% CI, 89.7-90.0), and a specificity of 91.1% (95% CI, 91.1-91.2) at the frame-level. At the patient-level, the DL model detected plaque erosion with an AUC of 0.901 (95% CI, 0.900-0.902), a sensitivity of 89.6% (95% CI, 89.4-89.8), and a specificity of 82.0% (95% CI, 81.9-82.2). Conclusion: A newly developed DL model enabled the accurate diagnosis of plaque erosion. This novel DL model will help cardiologists make an accurate diagnosis of plaque erosion in patients with ACS.
Abstract P364: Liraglutide Protects Against Angiotensin-induced Diastolic Dysfunction And Is Associated With Altered Acetyl-coa Metabolism
Authors: Cody A Rutledge, Mabel Lopez, Steven Mullett, Stacy Wendell, Eric Goetzman, Brett A Kaufman
Journal: Circulation Research (2021)

Background: The mechanisms underlying diastolic dysfunction remain complicated and poorly understood. Previously implicated mechanisms include increased interstitial fibrosis and oxidative damage, altered calcium handling, and mitochondrial dysfunction. In this study, we investigate changes in the cardiac metabolic profile from mice with Angiotensin-II (Ang)-induced diastolic dysfunction. Because treatment with the GLP-1 agonist liraglutide (Lira) relieves Ang-induced diastolic dysfunction, we examined altered metabolites in Ang and Ang+Lira mice to identify metabolic pathways involved. Methods: 8-wk mice were implanted with Ang pumps (1000 ng/kg/min) +/- Lira (0.2 mg/kg/day) therapy for 4 wks and compared to sham mice. Baseline and 4-wk echocardiography was performed. Hearts were collected for RNA-sequencing, Western blot, histology, radiolabeled palmitate assay, and targeted metabolomics by liquid chromatography-mass spectrometry to assess metabolic changes. Results: After Ang treatment, mice had significant diastolic dysfunction but only mild hypertrophy based on echo and histologic measures and no evidence of systolic change. Compared to sham mice, Ang mice had reduced E/A (Sham, 2.67±0.40; Ang, 1.71±0.11; p&lt;0.05) and peak reverse longitudinal strain rate (rLSR;Sham, 8.48±0.65/s; Ang, 6.081±0.33/s; p&lt;0.05, consistent with diastolic dysfunction. Ang+Lira mice had improved E/A (3.57±0.50, p&lt;0.01 vs. Ang) and rLSR (8.65±0.68/s, p&lt;0.01 vs Ang). Targeted metabolomic analysis of hearts found significantly increased accumulation of Acetyl-CoA in Ang mice (peak area 0.14±0.02) compared to sham (0.04±0.02 ,p&lt;0.05) that is restored by Lira therapy (0.02±0.01 ,p&lt;0.05 vs sham and Ang). A radiolabeled palmitate oxidation assay found decreased palmitate oxidation in both Ang and Ang+Lira mice compared to sham, but interestingly, also demonstrated significantly lower acid soluble metabolite oxidation in the Ang+Lira mice vs. Ang alone. Conclusions: We found that Ang-treated mice accumulate myocardial Acetyl-CoA, suggesting a defect in TCA flux. Lira resolves the increase in Acetyl-CoA and improved measures of diastolic dysfunction. This data may implicate a novel metabolic pathway in the development of diastolic disease.
Abstract 9860: P38MAPK Deficiency in VSMCs Mitigates Abdominal Aortic Aneurysm and Atherosclerosis Progression via Promoting MKL1 Ubiquitin Proteasome Degradation
Authors: Shengshuai Shan, Jinjing Zhao, Pan Gao, Orazio Slivano, Wei Zhang, Xiaochun Long
Journal: Circulation (2021)

Cardiovascular diseases (CVD) are the leading cause of death in developed countries. Two major manifestations of CVD are aortic aneurysm and atherosclerosis, which are devastating and lack effective pharmacological therapy. The stress responsive pathway, p38 mitogen-activated protein kinase (MAPK), has been reported as a pivotal regulator in diverse processes, including cell proliferation, migration, inflammation, and apoptosis, contributing to cardiovascular development and pathology. However, a detailed understanding of the mechanistic role of p38MAPK in vascular smooth muscle cells (VSMCs) in the pathogenesis of aortic aneurysm and atherosclerosis has yet to be elucidated. Using a VSMC-specific lineage tracing reporter system, we showed that the phosphorylated form of p38MAPK (p-p38MAPK) was markedly elevated in VSMCs of aneurysmal vessels. VSMC-specific p38α ( Mapk14 ) knockout mice displayed attenuated abdominal aortic aneurysm (AAA) and atherosclerotic lesion formation compared to wild-type control mice. Further, loss of MAPK14 in VSMCs abolished the protein expression of multiple ER stress markers, including BIP, Protein Disulfide Isomerase (PDI), and ATF4, which was accompanied by the downregulation of the cleaved Caspase-3 and upregulation of BCL2 protein. This indicates a crucial role of p38MAPK in potentiating ER stress and apoptosis. Interestingly, aortas from VSMC-MAPK14 null mice displayed dramatically reduced protein levels of MKL1, a vital transcription factor with a well-recognized role in promoting AAA and atherosclerosis progression via regulating vascular apoptosis. In vitro, deficiency of p38MAPK in VSMCs via siRNA or SB203580, a selective inhibitor of p38MAPK pathway, downregulated whereas forced expression of MKK6 (activates p38MAPK) increased MKL1 protein expression. Finally, activation of p38MAPK inhibited MKL1 ubiquitination, which was partially rescued by SB203580. Collectively, our data demonstrated a critical role of VSMC-p38MAPK in promoting AAA and atherosclerosis progression, likely through stabilization of MKL1 via p38MAPK-dependent inhibition of MKL1 ubiquitin proteasome degradation.
Bone Marrow-Based Biomarkers for Predicting aGVHD Using Targeted RNA Next Generation Sequencing and Machine Learning
Authors: Maher Albitar, Hong Zhang, Andrew L. Pecora, Andrew Ip, Andre H. Goy, Spiraggelos Antzoulatos, Ivan De Dios, Wanlong Ma, Sukhdeep Kaur, Hyung C. Suh, Michele L. Donato, Scott D. Rowley
Journal: Blood (2021)
Abstract P428: A New Mouse Model Of Myocardial Lipids, Fibrosis, Arrhythmia And Diastolic Dysfunction Induced By Hyperlipidemia And Cardiac LDLR
Authors: Monique Williams, Camila Iansen Irion, Jose Manuel Condor Capcha, Guerline Lambert, Grace Seo, Jeffrey J Goldberger, Lina A Shehadeh
Journal: Circulation Research (2021)

Background: Hyperlipidemia is a major risk factor for CVD. Patients with HF with preserved ejection fraction (HFpEF) have more myocardial lipid accumulation than patients with reduced EF (HFrEF). RNASeq data from cardiac biopsies showed downregulation of the gene for lipoprotein lipase (LPL) that degrades triglycerides, in HFpEF patients compared to healthy and HFrEF controls. Poloxamer-407 (p407) induces hyperlipidemia by blocking LPL and subsequent increase in plasma triglycerides and low-density lipoprotein (LDL) cholesterol. We hypothesized that mice treated with p407 and cardiac LDL-Receptor (LDLR) over-expression (OE) develop hyperlipidemia, myocardial lipid accumulation, and diastolic dysfunction resulting in HFpEF and arrhythmias. Methods: Baseline cardiac function was assessed by echo for male and female C57Bl6 mice (n=9) for 2 groups: 4wk biweekly i.p. p407-injections with (n=4) or without (n=3) single i.v. injection with AAV9-cTnT-LDLR. Cardiac function was assessed by echocardiography at 3 and 4 wks. Blood Pressure (BP) and Whole Body Plethysmography (WBP) were assessed during wk4. Ttest was used for statistics. PR and ORO staining and telemetry were performed at wk4. Results: At wk3, P407 and LDLR OE led to alterations in diastolic function (increased IVCT, IVRT, MV E/E’, MPI, and NFT) and increased LV wall thickness, p&lt;0.05. At wk4, there was pulmonary hypertension (increased mean pulmonary arterial pressure, decreased pulmonary acceleration time p &lt;.05).Histology showed excessive myocardial lipids and fibrosis, and telemetry showed incidents of second-degree and higher-degree AV block. The group injected solely with p407 show e d alterations in diastolic function (increased IVCT, IVRT, NFT, LVMPI, LVMPI NFT p&lt;.05 ) and decreased EDV, ESV, EDLVM, ESLVM, p&lt;.05 at wk4. All groups had preserved %EF and no abnormalities in BP or WBP. Conclusions: P407 and cardiac LDLR OE induce a drastic decline in cardiac diastolic function over a shorter period of time compared to p407 alone. Diastolic dysfunction was observed in wk3 followed by pulmonary hypertension, arrhythmia, myocardial lipid accumulation and fibrosis in wk4. This new model may allow for more rapid investigations of cardiac abnormalities seen in HFpEF patients.
INNV-42. ACTIVE VS RECEPTIVE MUSIC LISTENING THERAPY IN BREAST CANCER PATIENTS USING ARMCAN
Authors: Soma Sengupta, Claudia Rebola, Rhonna Shatz, Abigail Koehler, Yehudit Rothman, Abdelkader Mahammedi, Michelle Kirschner
Journal: Neuro-Oncology (2021)

Abstract Secondary brain tumors and neurocognitive damage from radiation or chemotherapy are often the commonest neuro-oncological problems in cancer. Breast cancer is the most commonly diagnosed cancer in women, with approximately 2 million women diagnosed in 2018.1 The 10-year survival rate for women diagnosed with breast cancer is 78% (World Cancer Research Fund, 2018). Although the 10-year survival rate is high, women who undergo chemotherapy can experience neurocognitive impairment resulting in significant effects of their cognitive functioning.2 Chemo related dysfunction is known as “chemobrain” or “chemofog.” Chemobrain can result in difficulty with attention, daily activities of living, and memory. This impacts people’s livelihoods and affects their general well-being. Current research on the topic of chemobrain in breast cancer survivors is minimal. However, this study aims to reduce the post-chemotherapy outcomes of chemobrain through the use of interactive versus receptive music. “Brain Fog” or chemobrain is the basis of significant neurological morbidities in the breast cancer population. It causes difficulty in people being able to even carry out activities of daily living. We have developed a prototype “ARMCan—a music software application to help breast cancer patients with “brain fog.” We are conducting a pilot feasibility study to beta test this interactive application which will promote executive function recovery in breast cancer patients with chemobrain.
Treatment Patterns and Economic Burden Among Elderly Patients with Acute Myeloid Leukemia Treated with Hypomethylating Agents: A SEER-Medicare Analysis
Authors: Andrew M. Brunner, David Huggar, Ronda Copher, Zheng-Yi Zhou, Miriam L. Zichlin, Annika Anderson, Nathaniel Downes, Ali McBride
Journal: Blood (2021)