tbuckley/cabot-search huggingface dataset:
Abstract 14089: Phase Shift Microbubbles for the Treatment of Microvascular Obstruction
Authors: Soheb Anwar Mohammed, Xucai Chen, Maria Fernanda F Acosta, Dillon Hanrahan, Evan C Unger, Emmanuelle J MEUILLET, John Pacella
Journal: Circulation (2021)

Introduction: Microvascular obstruction (MVO) following coronary intervention is a common problem associated with worse clinical outcome, and has no consistent therapy. We are developing a new technique termed sonoreperfusion (SRP), to restore microvascular patency. This entails the use of ultrasound (US) to cause microbubble (MB) cavitation to dissolve microthrombi; this MB cavitation creates shear stress, activates nitric oxide release, and results in thrombolysis. In this pilot study, to further optimize SRP, we have used Phase Shift Microbubbles (PSMBs) (Microvascular Therapeutics, Inc). Owing to their much smaller size relative to standard MBs (~400 nm vs 3 μm) and greater microthrombus penetration, we will test the hypothesis that PSMBs attain successful reperfusion of MVO, and ultimately, will provide more rapid SRP, in our model of MVO. Methods: MVO of the rat ( n =3) hindlimb was created by direct injection of microthrombi into the left femoral artery, followed by infusion of therapeutic PSMBs. Definity MBs (Lantheus Medical Imaging) were infused through the jugular vein for contrast enhanced ultrasound imaging (CEUS). A transducer was positioned vertically above the hindlimb for therapeutic US pulses during concomitant administration of PSMBs. CEUS cine loops with burst replenishment were obtained at baseline (BL), 10 min post MVO, and after each of the two SRP treatment sessions (TX1, TX2) and analyzed (MATLAB). Results: Fig. 1 depicts a typical example demonstrating successful creation of MVO and complete reperfusion after SRP treatment. Data are expressed as mean ± standard error. Blood volume (dB) at BL (15.3 ± 1.1), MVO (5.2 ± 1.3), TX1 (19.8 ± 2.4), TX2 (17.9 ± 1.8) and flow rate (dB/sec) at BL (2.7 ± 0.4), MVO (0.2 ± 0.1) TX1 (2.1 ± 0.5), TX2 (2.7 ± 0.4). Conclusions: US targeted PSMB cavitation causes successful rapid reperfusion of rat hindlimb following MVO. Studies to explore the underlying molecular mechanisms associated with SRP of PSMBs are underway.
Abstract 11896: Building Capacity for a Patient-Centered Research Agenda on Racial and Sex-Specific Cardiovascular Disease Disparities in COVID-19
Authors: Deborah L Crabbe, Alice Hausman, Briana Richardson, Elyse Castillo, Amy Confair, Sabrina Islam, Gabriel Tajeu, Krys Johnson, Heather Gardiner
Journal: Circulation (2021)

Introduction: African Americans (AA) and women are under-represented in clinical research. Barriers to including AA’s and women as research partners include fear, distrust, and a poor understanding of the research process. COVID-19 could be an opportunity to engage under-represented minorities and women in the research process. Objectives: The goal of this project was to build stakeholder capacity for patient-centered outcomes research (PCOR) and incorporate the perspectives of AA and female patients in developing a research agenda and questions suitable for use in the AHA COVID-19 CVD Quality Improvement Registry (AHA-R). The final research agenda will address the racial/sex-specific CVD disparities in COVID-19. Methods: Using community participatory principles, we established a network of stakeholders (AA patients, women, and researchers). Stakeholders were recruited to participate in focus group (FG) interviews and Town Hall (TH) meetings. All activities were held virtually and recorded. Videos and transcripts were independently reviewed. A Research advisory council (RAC, n=8) was recruited from a subset of stakeholders. RAC members received monthly research training using the PCOR Institute’s resources. RAC members attended a training workshop on narrative medicine principles and were encouraged to share their own experiences. The program sponsored 2 Facebook live events and conducted a survey to acquire and share compelling real-life COVID health stories. The questions generated from the FG, TH and RAC were prioritized by the RAC to create a research agenda and questions suitable for inquiry using AHA-R. Results: The program educated participants on CVD complications related to COVID (TH =51, 84% AA, 78% women), (FG =28, 93% AA, 82% women). There were 53 questions and 7 compelling narratives generated covering 7 topics. Topics included: COVID with and w/o heart disease, research, COVID and pregnancy, stress, racism, and general heart disease. In both groups, feedback on research results was cited as an important factor for participation in research activities. Conclusions: The project developed a research ready stakeholder network, and a prioritized research agenda about CVD disparities in COVID-19 suitable for inquiry using AHA-R.
Abstract 11649: GLP-1 Receptor Agonists in Heart Failure: Insights From a Cardiometabolic Center of Excellence
Authors: Yasser Sammour, Michael Nassif, Preetham Gunta, Fengming Tang, melissa magwire, Timothy Fendler, Taiyeb Khumri, Anthony Magalski, James H O'Keefe, Brett Sperry, Mikhail N Kosiborod
Journal: Circulation (2021)

Background: Data regarding the use of GLP-1 receptor agonists (GLP-1RA) in patients with established heart failure (HF) remain limited. Methods: We included patients with established HF treated at Cardiometabolic Center (CMC) between January 2019 and December 2020 who had at least two visits and received GLP-1RA. We compared change in outcomes of interest between baseline and last CMC visit. Results: Among 151 HF patients treated with GLP-1RA, 88 had HF with reduced ejection fraction (HFrEF) and 63 had preserved ejection fraction (HFpEF); 92% had type 2 diabetes (T2D), the rest had prediabetes, and 27% were on SGLT-2i at baseline. After a median follow-up of 6.6 (3.7-11) months, 92% of patients remained on GLP-1RA, (64% were also receiving SGLT-2i at last follow up). The median time on GLP-1RA therapy was 5.4 (3-9.7) months with HFrEF, and 6.1 (3.4-11.8) months with HFpEF. We observed reductions in median total daily insulin doses in both HFrEF and HFpEF patients (from 60 to 39 units, and 53 to 31 units, respectively, p&lt;0.001 for both), mean HbA1c (7.7% to 6.9%, p&lt;0.001 and 7.2% to 6.8%, p=0.002 respectively), and mean percent body weight (-6.2% and -7.9% respectively, p&lt;0.001 for both) ( Figure ). Additionally, lower rates of hospitalizations or urgent visits for HF were seen in those with HFrEF [13.6% vs. 34.1% (p&lt;0.001)], and HFpEF [from 15.9% vs. 33.3% (p=0.01)] during follow-up time compared with an equal duration prior to care at CMC (6.3 months with HFrEF, and 6.9 months with HFpEF). GLP-1RA therapy was generally well-tolerated with side effects in 31% of patients (mainly gastrointestinal complaints), but only 6% required drug discontinuation. Three patients stopped GLP-1RA due to cost. Conclusion: GLP-1RA therapy (in combination with SGLT-2i in most patients) was well-tolerated in both HFrEF and HFpEF, and was associated with significant reductions in insulin dose, HbA1c, body weight, and lower risk of hospitalizations or urgent visits for HF after initiation of therapy.
Abstract 10319: Community Socioeconomic and Urban-Rural Differences in Emergency Medical Services Time Intervals for Suspected Stroke Patients in North Carolina
Authors: Srihari V Chari, Eric R Cui, Haylie E Fehl, Antonio R Fernandez, Jane H Brice, Mehul D Patel
Journal: Circulation (2021)

Introduction: Rapid emergency medical services (EMS) response, care, and transport of acute stroke patients increases the likelihood of receiving time-sensitive treatment. There is limited research on the relationship of community factors with prehospital delays in EMS management of stroke. We compared EMS prehospital time intervals for suspected stroke patients by community socioeconomic status (SES) and urban-rural status in North Carolina (NC). Methods: We analyzed 2019 NC EMS encounter data collected in the National EMS Information System Version 3 standard. Eligible patients were adults requiring a 911 call response by EMS for stroke-like symptoms and transport to the hospital. Incident street addresses were geocoded to census tracts using ArcGIS Pro and linked to SES data from the American Community Survey and rural-urban commuting area (RUCA) codes. Community SES was defined as high, medium, or low based on tertiles of the AHRQ SES index. Urban, suburban, and rural tracts were defined by RUCA codes 1, 2-6, and 7-10, respectively. Differences in mean times by community SES and urban-rural status were evaluated using Kruskal Wallis tests. Results: We identified 17,117 eligible EMS encounters of suspected stroke (65% (11,121 of 17,117) 65+ years old; 55% (9,330 of 17,117) female; 70% (11,839 of 17,117) White) from 2,028 tracts. Median response, scene, and transport times were 8 (interquartile range, IQR 6-11) min, 16 (IQR 12-20) min, and 14 (IQR 9-22) min, respectively. Mean transport times were shorter in low SES (16 min) than in medium and high SES communities (17 min, p&lt;.0001). Mean transport times were longer in rural (21 min) and suburban (19 min) than in urban tracts (14 min, p&lt;.0001). Conclusions: EMS transport times were on average longer for suspected stroke patients in rural but not in low SES tracts. Further research is needed on the role of community socioeconomic deprivation and rurality in contributing to delays in prehospital stroke care.
Spleen Stiffness By Magnetic Resonance Elastography or Ultrasound Elastography As a Surrogate Marker of Bone Marrow Fibrosis in Myelofibrosis Patients
Authors: Laura Coutinho Vassalli, Alex Freire Sandes, Angela Hissae Motoyama Caiado, Giuseppe D`Ippolito, Alberto Lobo Machado, Julio Tadeu Mendonça Gonçalves da Silva, Maria de Lourdes Chauffaille, Daniella Kerbauy
Journal: Blood (2021)
Potential Utility of Circulating Tumor DNA Monitoring in Primary Mediastinal B-Cell Lymphoma Treated with R-DA-EPOCH
Authors: Ana Jimenez-Ubieto, María Poza, Alejandro Martín-Muñoz, Sara Dorado, Yanira Heredia, Pilar Sarandeses, Carmen Bárcena, Laura Rufian, Miguel Canales, Alejandra Juarez, Antonia Rodriguez Izquierdo, Tycho Baumann, Carlos Grande, Ricardo Sanchez, Juan Manuel de la Rosa, Nieves López-Muñoz, Marta Hidalgo, Elena Vera, Miguel Gallardo, Inmaculada Rapado, Rosa Ayala, Joaquín Martínez-López, Santiago Barrio
Journal: Blood (2021)
Abstract 10389: Identifying High-Risk Clinical Phenogroups of Pulmonary Hypertension Through a Clustering Analysis
Authors: Paula Rambarat, Emily K Zern, Dongyu Wang, Shahrooz Zarbafian, Elizabeth E Liu, Jessica K Wang, Jenna N McNeill, Carl T Andrews, Eugene V Pomerantsev, Nathaniel Diamant, Puneet Batra, Steven A Lubitz, Michael H Picard, Jennifer E Ho
Journal: Circulation (2021)

Introduction: The classification and management of pulmonary hypertension (PH) is challenging due to clinical and hemodynamic heterogeneity of patients. We sought to identify distinct phenogroups of PH that are at particularly high-risk for adverse events. Methods: A hospital-based cohort of patients referred for right heart catheterization between 2005-2016 with PH (mean pulmonary artery pressure &gt; 20 mmHg at rest) were included. Key exclusion criteria were shock, cardiac arrest, cardiac transplant or valvular surgery. K-prototypes, an unsupervised clustering algorithm, was used to cluster patients into subgroups based on 11 clinical covariates. The optimal number of clusters was determined using the silhouette method. Results: Among 5208 patients with mean age 64 (SD 12) years, 39% women, we identified 6 phenogroups when clustering on baseline clinical comorbidities ( Table 1 ). Phenogroups 2 and 4 had the greatest baseline prevalence of heart failure (both) and diabetes (group 4). Over a median follow-up of 6.3 (IQR 3.6 to 9.8) years we observed 2182 deaths and 2002 major cardiovascular events (MACE). Phenogroups 2 and 4 had the highest risk for future adverse events including death (age and sex adjusted HR 1.33, 95% CI 1.05-1.68 and 1.42, 95% CI 1.13-1.77, each compared with the lowest risk group 3 respectively) and MACE (HR 5.97, 95% CI 4.83-7.38 and 4.06, 95% CI 3.30-4.99, compared with group 3 respectively; Figure 1 ). Conclusions: Cluster-based analyses identify patients with PH and specific comorbid cardiovascular burden that are at higher risk for adverse clinical outcomes. Further studies are needed to better understand clinical heterogeneity among patients with PH.
Abstract 10210: Automating Risk Assessment of Acute Kidney Injury for Patients Undergoing Percutaneous Coronary Intervention
Authors: Chenxi Huang, Karthik Murugiah, Amarnath Annapureddy, Wade Schulz, Frederick A Masoudi, John Rumsfeld, Bobak Mortazavi, Harlan M Krumholz
Journal: Circulation (2021)

Background: The risk of acute kidney injury (AKI) for percutaneous coronary intervention (PCI) can inform decision-making and mitigation. However, risk assessment is hampered by the burden of manually abstracting and inputting data required by the established model developed on registry data. Accordingly, there is a need to develop AKI models that use automatically extracted electronic health records (EHR) data and evaluate their performance in comparison to the contemporary registry model. Methods: We used EHR data for PCIs performed at Yale New Haven Hospital (YNHH) and the linked local National Cardiovascular Data Registry (NCDR) CathPCI data to develop and compare the EHR models with the NCDR model. AKI was defined as an increase of ≥0.3 mg/dL or 50% in serum creatinine. To maximize interoperability across systems and usability at the point of care, we only considered structured EHR readily extractable before PCI, and implemented simple but universal data preprocessing. Longitudinal data was aggregated into 24h, 7d and 14d prior to PCI. We used Lasso regression and gradient descent boosting (GDB) to train the models and tested their capacity to approximate the NCDR model predictions and predict AKI independently. We evaluated performance via cross-validation by c-statistic, calibration slope, and predictive range defined by event rate difference in the lowest and highest risk deciles. We used paired t tests for model comparison. Results: The cohort included 9,202 PCIs from December 2012 to November 2019 at YNHH for 8,445 patients and had a mean age of 67.0±12.0 years with 27.6% females and 798 (8.7%) AKIs. Evaluated on the same test sets, the EHR models approximating the NCDR model predictions achieved similar performance to that model (all p&gt;0.05). Further, the EHR model employing GDB to independently predict AKI achieved slightly better performance than the NCDR model in c-statistic (0.84 vs 0.83, p=0.02) and predictive range (41.2% vs 39.5%, p=0.13) with similar calibration (slope 0.98 vs 0.99). Conclusion: The automatically extracted EHR data produced models with similar performance to the registry model. These models can automate AKI risk assessment for PCI, alleviating provider burden and increase uptake of risk assessment.
Abstract 10132: Human Ipsc Derived Cardiac Tissue Matured by Spontaneous Traveling Waves for Improved Drug Assessment
Authors: Junjun Li, YING HUA, Xiang Qu, Nagako Sougawa, Yoshiki Sawa, Shigeru Miyagawa, Li Liu, Takuji Kawamura
Journal: Circulation (2021)

Introduction: The precise evaluation of safety and efficacy for newly developed medication is of vital importance for drug discovery. As a promising candidate for the drug assessment, the human iPSC derived cardiomyocytes (hiPSC-CMs) tend to be less mature than adult cardiomyocytes, which could limit their application. We developed spontaneous traveling waves (TW) to rapidly pace and mature hiPSC-CMs. We hypothesized that the TW-matured hiPSC-CMs could serve as a more accurate model for drug discovery and development. Method and Results: The silicone wells and pillars were mounted in petri dishes. hiPSC-CMs were plated into the wells to form close-loop tissue where TW originated and paced the CMs in most of the wells (83.33 ± 13.6%, 18 wells from 3 tests). After 14-day culture, the hiPSC-CMs were evaluated by immunostaining, gene expression, western blotting and electron microscopy. Micro electrode array (MEA) were used to evaluate the drug response of CMs. The TW paced the CMs to beat at a much higher rate than the group without TW (TW: 220 ± 74 bpm vs. Control: 32.4 ± 30.1 bpm, n = 18, p &lt; 0.0001, at day 6). After 14 day culture, TW group has significantly higher expression of myosin heavy chain beta, connexin 43, and myoglobin. Electron microscopy indicated TW CMs with larger sarcomeric bundles, well-defined Z disks and myofibrils. In addition, the TW group showed shortened QT interval, more close to the human adult level (female/male: 288 ± 21 and 237 ± 8 ms) than control group (TW: 280 ± 71 ms vs. Control: 460 ± 120 ms, n = 8, p = 0.0018). Moreover, TW group showed enhanced response to the β adrenoceptor agonist ( beat rate with 10 uM isoproterenol : TW: 111.1 ± 15.57 bpm vs. Control: 83.73 ± 10.92 bpm, n = 6, p = 0.0064 ). TW group showed significantly different response to sodium channel blocker and reduced data variation than control ( QT interval at 100 μM mexiletine: TW: 424.4 ± 74.7 ms, CV = 17.6% vs. Control: 694.57 ± 198.38 ms, CV = 28.6%, n = 4, p = 0.035). Conclusion: By creating the close-loop cardiac tissue, the traveling wave could spontaneously originate and rapidly pace hiPSC-CMs. The TW paced hiPSC-CMs showed improved sarcomeric and functional maturation, improved drug response with reduced data variation, holding potential as a robust and accurate candidate for drug discovery.
Abstract 12280: Exercise Chronotropic Response And Left Atrial Performance In Patients With Heart Failure
Authors: Tadafumi Sugimoto, Greta Generati, Maurizio Losito, Francesco Bandera, eleonora alfonzetti, Marco Guazzi
Journal: Circulation (2021)

Introduction: The hemodynamic impact of left atrial (LA) intrinsic properties in heart failure (HF) in relation to heart rate (HR) response to exercise has not received attention. Hypothesis: We aimed at investigating the link between LA stiffness and function vs HR reserve (rest to peak exercise) in patients with HF. Methods: A total of 191 patients with HF: 157 β blockers user (LVEF 38 ± 12%, HR reserve 42 ± 18 beats/min) and 34 Non-β blockers user (LVEF 45 ± 19%, HR reserve 36 ± 19 beats/min) underwent cardiopulmonary exercise testing combined with exercise Echo with assessment of LA strain. LA stiffness (median 0.84, IQR 0.44 to 1.89) was assessed using mitral E/E’ /LA strain ratio at rest. Results: HR reserve was positively associated with LA-strain both at rest (20 ± 11%, R = 0.29) and during exercise (20 ± 11%, R = 0.19), LA-strain rate [absolute value] both at rest (1.7 ± 1.0 /s, R = 0.27) and during exercise (1.6 ± 1.2 /s, R = 0.26) and peak VO 2 (14 ± 4 mL/kg/min, R = 0.62), and negatively associated with LA volume index (44 ± 23 ml/m 2 , R = -0.29), log-transformed LA stiffness (R = -0.35), mitral regurgitation (from 0 to 4+) both at rest (R = -0.28:) and peak exercise (R = -0.25) and VE/VCO 2 slope (32 ± 8, R = -0.32)(figure) (P&lt;0.05, respectively). There was no significant association between HR reserve and LVEF both at rest and peak exercise, stroke volume index (SVI) both at rest and peak exercise. In multivariable analysis HR reserve had a significant association with age and log-transformed LA stiffness (standardized β-coefficients: -0.17 and -0.22, P &lt;0.05, respectively) after adjusting for age, gender, hypertension, diabetes mellitus, β blockers use, ivabradine use, LA volume index, log-transformed LA stiffness, peak LVEF, peak SVI and peak mitral regurgitation ≥2. Conclusions: In HF patients, age and LA stiffness play a key role in HR response to exercise irrespective of β blockers prescription. These data may offer additional insights in the concepts of exercise limitation in HF.
Abrogation of a Histone Chaperone Pathway Mitigates Inflammation-Driven AML Progression
Authors: Hsin-Yun Lin, Mona M.Hosseini, Marina Villamor, John McClatchy, Sophia Jeng, Fatma Eryildiz, Andrew Adey, Shannon K. McWeeney, Travis Stracker, Anupriya Agarwal
Journal: Blood (2021)
Abstract 11351: Efficacy of Catheter Ablation for Atrial Fibrillation Across Race-Ethnicity
Authors: Bahaa Al-azzam, Annette Diaz, Taylor Tso, Miles Barney, Pranati Sreepathy, Mustafa Ali, Ishita Aggarwal, Miguel Perez, Victor Qiao, Ana Ongtengco, Sreenivas Konda, Erik Wissner, Dawood Darbar
Journal: Circulation (2021)

Introduction: Catheter ablation (CA) is now an established therapy for symptomatic atrial fibrillation (AF). Although the procedural success rate is high, the role of race-ethnicity and clinical predictors in preventing recurrence of AF remains unclear. Methods: Patients prospectively enrolled in an AF clinical-DNA biorepository and treated with CA for AF were included in the study. Recurrence of AF was assessed with symptom assessment, ECG, Holter, and event recorder evaluations in all patients during follow-up visits and Holter recordings were done when appropriate. Recurrence of AF was defined as AF detected &lt;12 months after CA. Results: Of the 238 enrolled, 84 (35.3%) were European American (EAs), 106 (44.5%) were African American (AA) and 48 (20.2%) were Hispanic American (HA). Baseline clinical characteristics were similar across the groups. Eighty-eight (37%) patients had AF recurrence within 12 months of CA. Multivariate analysis showed that compared to EAs, AAs (odds ratio [OR] 0.48, 95% confidence interval [CI]: 0.24-0.96, P+0.048) and HAs (OR 0.42, 95% CI: 0.18 - 0.94, P+0.048) are less likely to experience AF recurrence after CA (Table 1). Other clinical predictors included left atrial dilatation (OR 1.88, 95% 1.04 - 3.44, P+0.036), persistent AF (OR] 1.94, 95% [CI]: 1.04-3.64, P+0.074), valvular heart disease (VHD) (OR 2.66, 95% CI: 1.02-7.20; P=0.046) and history of smoking (OR 2.16, 95% CI: 1.18-3.99; P=0.012). Conclusion: We showed that clinical predictors of recurrence of AF after CA included left atrial dilatation, VHD, persistent AF and a history of smoking. Surprisingly, we found that AAs and HAs were less likely to experience AF recurrence than EAs and reasons for this differential response remains unclear.
Abstract 14017: Use of Cephalothin Prophylaxis in Artificial Cardiac Stimulation Procedures
Authors: Isabella Sa, Joceline Sa, Gabriella Sa, Sylton Melo
Journal: Circulation (2021)

Introduction: Antibiotic prophylaxis for artificial cardiac stimulation procedures is already established in clinical studies, however, it can be used in different prophylactic schemes and with different costs. Objective: To evaluate the effectiveness of cephalothin as a prophylactic antibiotic in artificial cardiac stimulation procedures. Secondly, to compare the cost of cephalothin with other well-established prophylaxis antibiotics in these procedures. Material and Methods: We assigned patients between 18 to 103 years old who had clinical recommendations for pacemaker implantation. In this retrospective study, we included all permanent artificial cardiac stimulation procedures with cephalothin prophylaxis realized between January 2011 and December 2020 at Hospital do Coração in Natal, Brazil. The prophylactic scheme was an intravenous infusion of cephalothin 2g administered 30 minutes before single-chamber, double-chamber implantation, and replacement pacemakers. Results: We performed 2,162 procedures and registered seven cases of postoperative infections (0.32%) after procedures. Besides, cephalothin is less expensive (U$1.35/1g - total U$5,887.81), compared to other well-established and commonly used antibiotics prophylaxis as cefazolin (U$2.91/1g - total U$12,596.00) or cefuroxime (U$7.24/750mg - total U$31,310.54). Conclusion: Cephalothin is effective in preventing postoperative infections in artificial cardiac stimulation procedures and has a better cost/dose than other well-established prophylaxis antibiotics.