tbuckley/cabot-search huggingface dataset:
Abstract 19097: Socioeconomic Disparities in Symptomatic Heart Failure in Patients With Acute Myeloid Leukemia
Authors: Yu Kang, Azin Vakilpour, Benedicte Lefebvre, Srinivas Denduluri, Amanda Smith, Marielle Scherrer-Crosbie
Journal: Circulation (2023)

Introduction: Patients with acute myeloid leukemia (AML) have a high risk of symptomatic heart failure (HF). In addition, socioeconomic status (SES) has a significant effect on cardiovascular health. However, little is known about the association of SES and HF in patients with AML. Hypothesis: To investigate the impact of SES in HF occurring after AML. Methods: All adult patients diagnosed with AML between August 2006 to November 2019 at the hospital of University of Pennsylvania were studied. The primary outcome was new-onset symptomatic HF defined by 2017 ACC/AHA guidelines. The median household income (MHI) was identified based on ZIP codes using the data.census.gov. Low-income was defined as MHI lower than the MHI of the United States in the same time period. Differences between low-income Black and other patients were determined using t-tests, chi-square or Mann Whitney U test. Fine and Gray’s subdistribution hazard regression analysis was used to identify characteristics associated with HF. Results: A total of 770 patients (404 men, age: 62±15 years) were included; 101 (13.1%) were Black, 669 (86.9%) White. Seventy-six patients (9.9%) experienced symptomatic HF during a median follow-up period of 442 days. The median time to HF was 106 days [46-243]. Seventy-six (75%) Black and 181 (27.1%) White patients had low-income. Low-income Black had more cardiovascular (CV) risks (≥ 2 CV risks 39.5% vs 25.1%, p=0.009) and more HF events (11 events, 19% vs 65 events, 9.1%, p=0.022), than other patients. No differences were noted in history of cardiovascular diseases, cardiovascular treatments, doses of anthracyclines, and non-cardiac death between low-income Black and other patients. The cumulative incidence of HF in low-income Black patients was higher (p=0.01). Low-income Black (HR: 2.02; 95% CI: 1.05 to 3.88; p=0.036) and hypertension (HR: 1.90; 95% CI: 1.14 to 3.16; p=0.014) were independent factors associated with HF. Conclusions: Low-income Black patients with AML have a higher rate of new-onset symptomatic HF, independently of their cardiovascular and cancer treatment. Whether these differences are due to genetic or environmental factors remains unknown.
Abstract 17405: Biodistribution, Dosimetry, and Specificity of A <sup>99m</sup> Tc-Labeled Matrix Metalloproteinase Targeted Radiotracer ( <sup>99m</sup> Tc-RP805) for Myocardial Infarct Imaging
Authors: Stephanie L Thorn, Lisa A Freeburg, Francis G Spinale, Albert J Sinusas
Journal: Circulation (2023)

Introduction: Activation of matrix metalloproteinase (MMPs) post myocardial infarction (MI) predicts post-MI remodeling. MMP activation in the heart can be detected using 99mTc-RP805 a radiolabel peptidomimetic that binds to the catalytic site. The purpose of this study was to evaluate the biodistribution, dosimetry, and specificity of clinical grade 99mTc-RP805 for first-in-human studies. Methods: Male and female rats (n=24) were injected with 99m Tc-RP805 and euthanized at 1, 3, 7 or 12 hr post injection to determine biodistribution and estimate human dosimetry. Organ activity (%ID/g) was used to estimate whole body and organ effective dose using OLINDA. MI was induced in rats by LAD ligation (n=19) and injected with 99m Tc-RP805 3 days post MI, and rats were euthanized 3 hr after injection in absence (n=9) or presence (n=10) of a 100 x blocking dose of RP805 (257 ug/kg) 30 min prior to radiotracer injection to establish specificity. In vivo SPECT/CT imaging was performed with GMP grade 99m Tc-RP805 in rats post-MI (n=4). Results: The %ID/g for each organ is presented per time point (Fig 1 A). The highest radiation dose was found in male kidneys at 3 hr (%ID/g: 6.11 ± 0.54), female kidneys at 1hr (%ID/g: 6.31 ± 0.88). The estimated total body dose for human males was calculated at 0.172 mSv/mCi and 0.283 mSv/mCi for females, equaling a dose of 3.4 mSv and 5.7 mSv for a 30 mCi injection in males and females, respectively. There is 4 fold increase 99mTc-RP805 uptake in the infarct area compared to the normal LV (Fig 1B) and uptake was blocked with cold compound (ANOVA, p&lt;0.001). In vivo SPECT/CT imaging with a newly synthesized GMP compound demonstrates uptake in the anterior LV (Fig 1C). Conclusions: We have developed and evaluated clinical grade 99m Tc-RP805 for targeted MMP imaging post-MI and demonstrated favorable dosimetry, biodistribution, and specificity for first-in-human imaging.
Abstract 14496: HIF2a Activation Reduces Pulmonary Angiogenesis and Promotes Vascular Remodeling in Pulmonary Arterial Hypertension by Suppressing Wnt7a Production in Pulmonary Endothelial Cells
Authors: Ankita Mitra, Dan Yi, Stuti Agarwal, Amy Tian, Xinguo Jiang, Mark Nicolls, Zhiyu Dai, Vinicio A Dejesus
Journal: Circulation (2023)

Introduction: Dysfunctional angiogenesis and obliterative vasculopathy are hallmarks of pulmonary arterial hypertension (PAH). Inappropriate HIF1a/2a activation and insufficient Wnt7a production are associated with pulmonary artery endothelial cell (PAEC) dysfunction, suggesting that HIF1a/2a and Wnt7a may interact as part of a signaling axis to promote PAEC homeostasis. Hypothesis: HIF1a/2a overactivation suppresses Wnt7a expression in PAH PAECs. Methods: Healthy and PAH PMVECs were obtained from explanted lungs. Cobalt Chloride (CoCl2) was used to activate HIF. PMVECs were transfected with lentiviruses carrying HIF1a/2a constructs, followed by functional and molecular studies. Lungs from mice with endothelial-specific HIF1a/2a activation (Egln1 Tie2Cre ) and HIF2a deletion (EH2) were analyzed via single cell (sc) RNA-seq and confocal imaging. Results: Compared to controls, PAH lung tissue and PAECs demonstrated an inverse correlation between increased HIF1a/2a, and reduced Wnt7a expression. Treatment with CoCl2 for 24 hours resulted in a ~4-fold increase in Wnt7a transcription that was absent in PAH PMVECs. Lentivirus transfection of healthy PAEC demonstrated that HIF1a increased Wnt7a transcription while HIF2a significantly reduced Wnt7a transcription. In silico analysis of the Wnt7a gene locus demonstrated HIF binding sites at promoter-enhancer sequences suggesting that Wnt7a is a gene target of HIF signaling. In addition, ATAC-seq and ChIP-seq analysis of the Wnt7a gene locus in PAH PMVECs indicated a closed chromatin configuration, suggesting epigenetic repression. Lung scRNA-seq and RNAScope analysis of Egln1 Tie2Cre mice demonstrated a reduction of capillary EC, which was absent in EH2 mice, suggesting a HIF2a-dependent mechanism. Confocal and WB of lung tissues demonstrate that Wnt7a expression was significantly reduced in Egln1 Tie2Cre mice but preserved in EH2 mice. Conclusions: HIF2a and epigenetic repression contribute to PAEC dysfunction by suppressing Wnt7a-dependent angiogenesis in PAH. We speculate that Wnt7a may also be required to maintain the capillary EC phenotype in the lung and that restoring Wnt7a production could compensate for HIF-driven endothelial dysfunction in PAH.
Abstract 13340: Contractility and Local Stress Patterns Depend on Directionality of Fibrosis Progression: Insights From Microscale Biomechanical Simulations
Authors: Aashild Telle, Mary Maleckar, Joakim Sundnes, Samuel T Wall, Patrick M Boyle
Journal: Circulation (2023)

Introduction: Cardiac fibrosis, a common pathological process in heart disease, leads to reduced contractility and increased myocardial stiffness. However, it remains unclear how various cellular and subcellular events individually contribute to these changes. Hypothesis: Tissue-scale biomechanical effects resulting from cellular and subcellular changes, such as myocyte loss and increased ECM stiffness, are anisotropic and depend on the prevailing direction of fibrosis progression. Methods: We used a mechanical modeling framework allowing for explicit geometrical representation of individual myocytes embedded in ECM. We used a transversely isotropic hyperelastic formulation for the cells while assuming the ECM to be isotropic. Contraction was imposed in each cell using an active stress model. In a simulated tissue domain (6х12 cells), we explored different cellular configurations (Fig. 1A) representing longitudinal, transverse, and random fibrosis progression (i.e., myocyte loss). In each configuration, we examined tissue shortening and stress distributions subject to original and 10х increased ECM stiffness. Results: Myocyte loss perpendicular to the myofiber direction had the largest impact on contractility (Fig. 1B and 1C; as low as 10.8% shortening vs. 15.4% at baseline). In particular, transverse stresses were greatly perturbed in areas near where remaining cells met replacement matrix. Longitudinal and random fibrosis progression had less impact on contractility but led to dramatic heterogeneity in stress distributions. Increased matrix stiffness (Fig. 1C) led to increased magnitude of all stress values. Conclusions: Tissue-scale changes depend on both ECM stiffening and the directionality of myocyte loss. Our model predicts that transverse fibrosis progression has the greatest impact on myocardial contraction, while longitudinal and random progression induce higher local maxima in myocardial stress distributions.
Abstract 14225: Cardiovascular Structural and Functional Changes Become Apparent With Increased Waist Circumference in Childhood Obesity
Authors: Kenji Harada, Yukiko Harada
Journal: Circulation (2023)

Background: Higher waist circumference (WC) is associated with cardiovascular disease, however, little is known about the association between WC and cardiovascular functional change in children. The purpose of this study is to examine the relationships between numbers of cardiovascular risk factors and left ventricular (LV) geometry and function in children. Methods: Echocardiography was performed in 401 children aged 7 to 13 years. Left atrial (LA) diameter, LV end-diastolic volume, ejection fraction, mass, mass-to-volume ratio, and carotid artery intima media-thickness (IMT) were measured. Transmitral peak flow velocities during early and late diastole and mitral annular myocardial velocities during early (Em) and late diastole (Am) were measured. LA systolic force and aortic stiffness were calculated. Lipids, uric acid, fasting glucose, insulin, high sensitive CRP, and homeostasis model assessment for insulin resistance (HOMA-IR) were also assessed. Subjects were divided into 4 groups: A group, WC within normal range; B group, increased WC; C group, increased WC plus any one of the following individual factors of hypertension, dyslipidemia (low high-density lipoprotein-cholesterol and/or high triglyceride), and raised fasting glucose; D group, metabolic syndrome. Results: Compared with the A group, LA diameter, mass/volume ratio, HOMA-IR, and uric acid were greater in the B group (p&lt;0.05 for all). With increasing number of metabolic syndrome disorders (C and D groups), dyslipidemia, increased Hs-CRP, decreased Em/Am, enhanced LA systolic force, increased IMT, and aortic stiffening were observed (Table). Conclusions: Higher WC is associated with insulin resistance, hyperuricemia, and concentric LV hypertrophy. Cardiovascular structural and functional changes become apparent with increasing number of metabolic syndrome disorders. Our findings suggest that primary prevention programs should be initiated in children with increased WC.
Abstract 15657: Stroke Survivors’ and Caregivers’ Experience of Using Game-Based Virtual Reality Training Modules Designed for Promoting Social Participation
Authors: Suzanne H Lo, Janita P Chau, Kai Chow Choi, Alexander Y Lau, Vivian W Lee, Chi Fai Eddie C Kwok, Thompson David, Robin Tianjiao T Zhang
Journal: Circulation (2023)

Introduction: Virtual reality (VR) technology may provide a promising alternative to promote stroke survivors’ social participation. Three innovative social participation-focused, game-based VR training modules for community-dwelling stroke survivors were developed. Aim: This study sought to understand the survivors’ and caregivers’ perceptions of the usefulness of VR-based interventions in supporting post-stroke recovery and their experience of using the specially developed VR modules. Methods: A qualitative study with semi-structured, in-depth, individual interviews was conducted with a convenience sample of 10 stroke survivor-caregiver dyads (n=20). Each survivor and caregiver attended a first interview about their perceptions and expectations of VR-based interventions. They were then invited to experience all games of the VR modules and were interviewed again about their experience and satisfaction with using the VR modules, and suggestions on areas for improvement. All interview data were transcribed verbatim and analyzed thematically. Results: Most of the survivors (mean age=60.80; SD=6.71) were female (70%), had an ischemic stroke (50%), and walked with a stick (70%). The mean years after stroke was 4.80 (SD=4.16). Most of the caregivers were female (80%) and had a mean age of 56.20 years (SD=7.73). All survivors had no prior VR experience. Three themes were identified: A modern strategy instilling enjoyment into the regular physical training; confidence boosting for reengaging into life situations and outdoor activities; and tailored modifications needed for reviewing training progress, supporting more social interactions and controller-free experience. They suggested enabling availability of the modules in survivors’ home or community settings for increasing the convenience to access the modules. Conclusions: The findings showed that the new VR training modules are acceptable to the survivors. Feedback elicited informed refinement of the modules and the usefulness of the modules in improving social participation of survivors will be evaluated in a large-scale randomized controlled trial.
Abstract 13943: Comparison of the Frequency and Time to True Ventricular Tachycardia Among Patients in the Cardiac, Medical/Surgical and Neurologic Intensive Care Units
Authors: Priya A Prasad, Jessica K Zegre-Hemsey, Mary Carey, Salah S Al-Zaiti, Claire E Sommargren, Lamberto Isola, David Mortara, Fabio Badilini, Michele M Pelter
Journal: Circulation (2023)

Introduction: Continuous ECG monitoring is the non-invasive gold standard used to identify ventricular tachycardia (VT), yet 87% of current bedside monitor VTs could be false. Therefore, knowing the burden of true VT is essential to guide treatment to those at greatest risk of poor outcomes. Hypothesis: When stratifying by intensive care unit (ICU) (cardiac, medical/surgical, neurological), there will be differences in: 1) demographic and clinical characteristics of patients with true VT; and 2) frequency and time to first true VT. Methods: Retrospective cohort study of adults admitted to an academic medical center ICU, 9/13-4/15. Potential VTs among 5,679 consecutive ICU patients were manually annotated by clinicians as true/false. Patient-level data were extracted from the health record. We used Kaplan-Meier and Cox proportional hazards methods to calculate time to first true VT and 60-day VT rate by ICU type. Results: There were differences in all characteristics examined (p&lt;0.0001)(Table) and frequency of true VT, stratified by ICU type (log-rank p&lt;0.0001)(Figure). After adjustment for age, gender, and risk factors (Table), CICU patients had a 42% increased rate (HR 1.42, 95% CI 1.16-1.74) and NICU patients had a 28% decreased rate of VT (HR 0.72, 95% CI 0.59-0.89) compared to M/SICU patients. Conclusion: Patients in the CICU experienced true VT much earlier (1.5 days) after admission than patients in the M/SICU and NICU. In addition, CICU patients had a higher rate of true VT and associated VT risk factors as compared to M/SICU and NICU patients. As expected, known cardiac risk factors are associated with true VT, but may be hidden among false alarms during bedside monitoring.
Abstract 16817: Comparison of Diagnostic Performance of Quantitative Perfusion Stress Myocardial Perfusion Imaging With Cardiac Magnetic Resonance Between Different Vasodilators
Authors: Patricia Rodriguez-Lozano, Shuo Wang, Haonan Wang, Ming-Yen Ng, Paul Kim, Amita Singh, Saima Mushtaq, Sin Tsun Hei, Yuko Tada, Elizabeth Hillier, Christian Østergaard Mariager, Michael Salerno, Gianluca Pontone, Javier Urmeneta, Ibrahim M Saeed, Hena Patel, Vicente Martinez, Alicia Maceira, Jose Monmeneu, Aju P Pazhenkottil, Mitchel Benovoy, Alborz Amir-Khalili, Martin A Janich, Andrew E Arai, Matthias G Friedrich, Amit R Patel
Journal: Circulation (2023)

Introduction: Adenosine and regadenoson are commonly used vasodilators in myocardial perfusion imaging for assessment of suspected coronary artery disease. Hypothesis: The aim of this study is to determine the difference between the different vasodilators by quantifying stress and rest myocardial perfusion using cardiovascular magnetic resonance (CMR). Methods: Subjects with known or suspected CAD from 10 centers undergoing invasive coronary angiography or CT angiography were enrolled for rest and stress first-pass perfusion images using dual sequence. First-pass stress perfusion images were acquired on 1.5T or 3.0T GE scanner during adenosine or Regadenoson. Fully quantitative perfusion values were determined using Fermi deconvolution. Significant CAD was defined by: presence of≥50% stenosis in the left main coronary artery or ≥70% in the one major vessel. Diagnostic performance of stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) was measured using receiver operating characteristics curves. Results: A total of 89 subjects were recruited with a median age of 66 yrs, 69% men, 55% significant CAD, history of hypertension in 78%, diabetes in 48%, and hyperlipidemia in 74%. 36 subjects used adenosine, while 53 used regadenoson as the vasodilator agent. Stress MBF had a good area under the curve for adenosine vs. regadenoson [ 0.89 (0.78-1.00) vs. 0.82 (0.66-0.98), p=0.43], sensitivity (100% vs. 84%), and specificity (80% vs. 80%). MPR had a higher area under the curve for adenosine than regadenoson [0.87 (0.75-0.98) vs. 0.68 (0.52-0.84), p=0.06], sensitivity (100% vs. 61%), and specificity (68% vs. 73%). (Figure) Conclusions: Our study showed that fully quantitative perfusion using CMR, regadenoson, and adenosine have similar good diagnostic accuracy when stress MBF was used as the diagnostic parameter. However, adenosine outperformed regadenoson for the detection of significant CAD when MPR was used as the diagnostic parameter.
Abstract 16172: Impella Use in Large Post-Infarct Ventricular Septal Rupture
Authors: John P Hintz, Daniel R Feldman, Hannah I Chaudry
Journal: Circulation (2023)

Background: Ventricular Septal Rupture (VSR) is a deleterious complication associated with myocardial infarction (MI). The most common form of mechanical circulatory support (MCS) utilized in post-MI complications is intra-aortic balloon pump (IABP). Impella is a far less commonly used modality as there is the potential for right-to-left shunting and a chance of mechanical perforation of the heart. Below is a case where an Impella 5.5 catheter was necessary to bridge a patient for surgical repair. Case presentation: A 76-year-old male patient presented to an outside hospital with an acute inferior ST-elevation myocardial infarction. He was treated with thrombolysis and was emergently taken to the catheterization lab where he underwent stenting of his RCA with plan to medically manage his non-culprit disease. His hospital course was complicated by cardiogenic shock with an echocardiogram that demonstrated a large VSR (Figure 1). A right heart catheterization demonstrated a significant left-to-right shunt (Qp/Qs ratio of 6:1) which necessitated mechanical support with an IABP as per standard of care. Post-IABP his Qp/Qs ratio improved to 1.6:1 but he continued to be under supported and remained in cardiogenic shock. Surgical repair of the VSR was planned for 1-week post-MI so he was transitioned to an Impella 5.5 catheter in order to stabilize and bridge him for surgery. Patient underwent surgical VSR repair and CABG on hospital day 7. Post-op he did well and was later discharged to rehabilitation center with subsequent recovery. Conclusions: If properly managed, utilization of an Impella catheter can be an effective tool to stabilize patients in post-MI VSR with refractory cardiogenic shock and bridge patients towards surgical repair. It is particularly effective when additional MCS support is required beyond the contemporary IABP and it can be used to stabilize patients for longer durations to ultimately avoid emergent surgery.
Abstract 13163: Clonal Hematopoiesis Risk Score is Associated With All-Cause and Cardiovascular Mortality in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Seyedmohammad Saadatagah, Md Mesbah Uddin, Lachelle D Weeks, Abhishek Niroula, Meng Ru, Koichi Takahashi, Steven Bradley, Bing Yu, Alexander G Bick, Benjamin L Ebert, Elizabeth A Platz, Pradeep Natarajan, Christie M Ballantyne
Journal: Circulation (2023)

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) is common in older adults, but the prognostic significance is unknown. We studied the prevalence of CHIP and its mortality in older adults and investigated whether the CHIP risk score (CHRS) -tool to predict hematologic malignancies (HM)- is associated with mortality in this population. Method: In ARIC cohort, CHIP was identified using exome sequencing, and CHRS scores were calculated using demographic, blood parameters, and molecular features. Individuals with CHIP were categorized into low- (CHRS≤9.5), intermediate- (9.5&lt;CHRS&lt;12.5), and high-risk (CHRS ≥12.5) groups. The primary outcome was all-cause death, and secondary outcomes were death from HM and cardiovascular disease (CVD). Results: In 3871 participants without a history of HM (aged 75.7 ± 5.2 years, 58.5% female, 23.1% Black), we identified 938 (24.2%) with CHIP, of whom 562 (59.9%) were low risk, 318 (33.9%) intermediate risk, and 58 (6.2%) high risk by the CHRS. During a median follow-up of 7.13 years, 570 (19.4%) deaths occurred in participants without CHIP and 128 (22.8%), 93 (29.2%), and 33 (56.9%), in the CHRS groups, respectively. Using multivariable competing risk regression, the hazard ratio HR (95% confidence interval) for all-cause mortality was 1.09 (0.90-1.32, P = 0.35), 1.13 (0.90-1.42, P = 0.29), 2.57 (1.75-3.77, P &lt;0.001), for low-, intermediate-, and high-risk CHIP, respectively. ( Fig. 1A ) Compared to those without CHIP, in the high-risk CHIP, the HR of death from HM (6 deaths of 58, 10.3%) was 25.92 (8.04-83.57, P &lt;0.001) and from CVD (12 of 58, 20.7%) was 2.97 (1.59-5.53, P &lt;0.001). ( Fig. 1B ). Conclusions: CHIP can be identified in one-fourth of older adults, and most were low-risk and had the same survival. However, individuals with high-risk CHIP face not only an elevated risk of death from HM but also a threefold higher risk of death from CVD. The latter was the most common cause of death in this group. Funding: NHLBI, NCI, NPCR