tbuckley/cabot-search huggingface dataset:
Abstract 15455: Unraveling the Mechanism of Ischemia in Pediatric Patients With R-AAOCA: Fixed and Dynamic Obstruction
Authors: Lindsay Eilers, Tam Doan, Srinath Gowda, Athar Qureshi, Shagun Sachdeva, Ziyad Binsalamah, Dana Reaves-O’Neal, Silvana M Molossi
Journal: Circulation (2023)

Introduction: Although rare, anomalous aortic origin of the right coronary artery (R-AAOCA) is associated with exercise-related sudden cardiac death and dynamic obstruction to coronary flow in the intramural segment has been proposed as the ischemia mechanism. We aim to describe fixed and dynamic obstruction mechanism of ischemia in select group of R-AAOCA patients undergoing invasive transcatheter stress FFR and iFR. Hypothesis: Ischemia in R-AAOCA involves a 2-tier mechanism involving both fixed and dynamic obstruction. Methods: Single institution retrospective study of R-AAOCA patients undergoing cardiac catheterization due to ischemic symptoms and negative perfusion defects on dobutamine stress CMRI. Coronary angiography was performed in all patients. Instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) were performed at baseline and under pharmacologic stress with adenosine (aFFR)/dobutamine (diFR) when the coronary ostium was engaged in a stable manner. Significant fixed obstruction was considered if aFFR&lt;0.80 and dynamic if diFR &lt;0.85. Results: A total of 14/446 (3%) R-AAOCA patients were included. In 10 patients, a Verrata pressure guide wire (Volcano, San Diego, CA) was able to be advanced to perform iFR and FFR. Fixed RCA obstruction was demonstrated in 4/10 patients (40%) and 2 of these (2/10, 20%) also had dynamic RCA obstruction (Table). All 4 patients were referred to surgery: 3 completed, 1 pending. In 4/14 (28%) patients, iFR and FFR were not performed due to inability to engage the RCA ostium, all of which found to be hypoplastic (1-1.5 mm) and slit-like at surgery. There were no procedural complications. Conclusions: In a small cohort of R-AAOCA patients, mechanisms for myocardial ischemia during stress suggest dynamic and fixed components. Our preliminary results provide important insight for risk stratification. Long-term follow-up will be important to validate the performance of iFR/FFR in R-AAOCA
Abstract 17220: Mathematical Modeling of Echocardiographic Underestimation of Right Ventricular Systolic Pressure in Severe Tricuspid Regurgitation
Authors: Tyler J Smith, Vinesh Appadurai, Muhammed Gercek, Kameswari Maganti, Jeesoo Lee, Michael Markl, James D Thomas
Journal: Circulation (2023)

Background: Echocardiography approximates right ventricular systolic pressure (RVSP) by the simplified Bernoulli Equation (SBE), adding mean right atrial pressure (mRA) to convective pressure (4v 2 ), where v is maximal tricuspid regurgitant (TR) velocity. As TR worsens, the inertance of TR flow increases which may cause TR peak velocity to lag behind the maximal RVSP time point. As a result, using SBE may underestimate RVSP in patients with significant TR. Currently, inertance is not measurable by echo, but theory suggests it is linearly related to regurgitant orifice diameter (3 X ROD). We sought to confirm the principle of RVSP underestimation in ≥severe TR by comparing a lumped parameter model (LPM) of the heart to cath/echo data. Methods: In MATLAB, the LPM uses time-varying elastance of atria/ventricles and the complete Bernoulli equation to model pressure and flow in all chambers/vascular beds. LPM parameters for trace and torrential TR cases yielded convective, inertial, RA and RV pressure curves and critical TR variables: TR volume, mRA, and TR velocity, which were compared to simultaneous cath/echo data in clinical patients. Results: Trace TR pressure curves aligned with RVSP and convective pressure peaks, and near perfect echo prediction. Torrential TR pressure curves show earlier peak RVSP with up to 20mmHg of inertial pressure, resulting in predicted 3.1mmHg underestimation, closely matching the observed underestimation of 3.6mmHg. For modeling demonstration, we show (from 90 subjects) 1 patient with trace TR (ROD 1.1mm), A, and 1 patient with torrential TR (ROD=11.3mm), B, in Figure 1. Conclusions: Our analysis shows the importance of inertial pressure in ≥severe TR: earlier peak RVSP congruent with accelerating increased regurgitant mass and improved approximation of RVSP by inertial pressure quantification modeling. Further clinical study of RVSP underestimation in cases of ≥severe TR and its correction by including inertial forces is recommended.
Abstract 15296: Incidence and Predictive Factors for Left Ventricular Dysfunction After Transcatheter Device Closure of Patent Ductus Arteriosus in Extremely Low Birth Weight Infants
Authors: Marissa E Adamson, Allen Ligon, Shannon Hamrick, Marcos Mills, Shazia Bhombal, Sarah E Hash, Erik Michelfelder
Journal: Circulation (2023)

Background: Left ventricular (LV) dysfunction is a known complication after ligation or device closure of patent ductus arteriosus (PDA). Recently, an increasing number of premature and extremely low birth weight (ELBW) infants undergo transcatheter device closure of PDAs. Afterload sensitivity of the immature myocardium may be expected to result in important changes in LV ejection fraction (EF) post-procedure. Aim: To evaluate incidence and magnitude of LV dysfunction after device closure of PDA in ELBW infants. Methods: Subjects undergoing PDA device closure from 2020-2022 who were ELBW (&lt;1 kg) and extremely premature (gestational age &lt;29 weeks) at birth were included. A single cardiologist reviewed each pre- and post-intervention echocardiogram and calculated LVEF. Mildly depressed function was defined as an LVEF &lt;53%, moderately depressed as LVEF &lt;40% and severely depressed as LVEF &lt;30%. Results: There were 62 subjects who met inclusion criteria. Mean gestational age and birth weight were 24.8 weeks and 646 g, respectively. Mean age and weight at intervention were 7.9 weeks and 1718 g, respectively. All patients had normal LVEF pre-procedure (mean LVEF 68%) with a significant decline post-procedure to 60% (p&lt;0.001) (Figure). Post-procedure, 80.6% of subjects maintained normal LVEF. Of 12 subjects who developed depressed function, 83% (n=10) had mildly depressed function and 17% (n=2) had moderately depressed function. There was no significant difference in post-procedure LV dysfunction in relation to pre-procedural PDA size, left atrial dilation, or LV dilation on univariate analysis. All subjects recovered function without additional inotropic support with a median time to observed normal LVEF of 5 days. Conclusions: LV dysfunction develops in 19% of ELBW infants undergoing PDA device occlusion, is usually mild in severity, and normalizes in all subjects. The size of PDA or degree of left heart dilation does not predict LV dysfunction in this population.
Abstract 15416: High Neighbourhood-Level Material Deprivation is Associated With Increased Rates of Cardiovascular Outcomes in Patients With ASCVD: A Population-Based Cohort Study
Authors: Maya S Sheth, Irene Jeong, Anna Chu, Shalane Basque, Jiming Fang, Peter C Austin, Candace D McNaughton, Husam M Abdel-Qadir, Dennis T Ko, Douglas S Lee, Jacob A Udell
Journal: Circulation (2023)

Background: Disparities in atherosclerotic cardiovascular disease (ASCVD) may persist even in jurisdictions with universal health care. The aim of this study was to examine the relationship between material deprivation and cardiovascular (CV) events in a population with established ASCVD. Methods: This population-based cohort study identified individuals in Ontario, Canada ≥66 years old as of January 1, 2019, with an ASCVD event in the prior 10 years. The primary exposure was neighbourhood-level material deprivation, denoting the inability to attain basic material needs, categorized into quintiles, from Q1 (least deprived) to Q5 (most deprived). Cause-specific hazard models estimated the association between material deprivation and CV outcomes over 3 years, adjusted for baseline characteristics. Trend tests across deprivation quintiles were performed. Results: Among 195,742 individuals with established ASCVD (median age 76 years, 37.3% female), individuals in the most deprived neighbourhoods (Q5) had higher rates of co-morbid conditions and CV disease, including myocardial infarction (MI), angina, peripheral artery disease, and coronary artery bypass grafts, compared to those in the least deprived neighbourhoods (Q1). Q5 residents had higher hazards of the composite outcome of all-cause death, MI, or stroke (hazard ratio [HR], 1.20 [95% CI, 1.16-1.24]), and component outcomes: all-cause death (HR, 1.23 [95% CI, 1.19-1.28]), MI (HR, 1.20 [95% CI, 1.11-1.31]), stroke (HR, 1.13 [95% CI, 1.03-1.23]), and heart failure (HR, 1.22 [95% CI, 1.16-1.28]), compared to Q1 residents. There were no significant differences for Q5 versus Q1 for coronary revascularization (HR, 0.97 [95% CI, 0.90-1.04]). We observed a progressive increase in risk across each quintile of deprivation (P-trend &lt;0.05 for all outcomes). Conclusion: Despite universal health care, increasing deprivation was independently associated with higher rates of CV outcomes.
Abstract 17093: The 3D T-Tubule Network Significantly Remodels in Cardiomyocytes Subjected to Mechanical Load
Authors: Leo Song, Vasiliki Courelli, Alexia Vite, Benjamin Prosser, Kenneth B Margulies, Michael Ibrahim
Journal: Circulation (2023)

Introduction: T-tubules (TT) are critical for excitation-contraction coupling in cardiomyocytes (CMs). Past work studying heart failure has spatially localized TT loss with inhibited Ca2+ release in the 2D space. This limited view does not consider tubules in other z-planes, necessitating a 3D understanding of the network. Hypothesis: We hypothesize that the ultrastructure of the 3D TT network significantly remodels in response to increase in culture substrate stiffness. Methods: Adult rat ventricular CMs were cultured ex vivo on substrate with either physiological stiffness (10 kPa) or pathological stiffness (50 kPa) for 2 days. Live CMs were stained for TTs (Di-8-ANEPPS) and Ca2+ (Fluo-4). 3D renderings of the TT network were reconstructed from z-stacks of 2D confocal images in the Arivis software. Within a set 3D region of interest, orientation (longitudinal, transverse, axial), volume, and surface area of tubules were measured. Ca2+ transients were taken from a line scan. Data from 18 CMs cultured at 10 kPa and 15 CMs cultured at 50 kPa were acquired. Results: CMs cultured on 50 kPa surfaces exhibited a decrease in the number of transverse elements (147 to 112) and an increase for longitudinal elements (3 to 16) compared to control CMs cultured on 10 kPa surfaces. For all 3 orientations, the volume of the average tubule increased by at least 20% following culture on 50 kPa surfaces. The total surface area of all axial and longitudinal tubules increased by at least 130% and decreased by 13% for all transverse tubules following culture on 50 kPa surfaces. Conclusions: Two days of culture on stiffened surfaces, designed to mimic the stiffness of diseased hearts, produces significant TT remodeling. Our work suggests that the remodeled TT network has less spatial capacity to release Ca2+ and worsened access to actin-myosin sites. In the future, we will associate the distance between each pixel on the line scan to the nearest TT with Ca2+ release parameters. This model system will permit further elucidation of how particular aspects of TT remodeling affect Ca2+ release and will facilitate testing of therapeutic interventions designed to prevent load-dependent defects in excitation-contraction coupling.
Abstract 16973: Using an in-vitro and ex-vivo Test Platform for Evaluation of a Pen-Sized Ultrasound Vascular Access Device (Vu-Path)
Authors: Sofia I Hernandez-Torres, Eric J Snider, David M Berard, Robert Rothstein, Theodore Abraham
Journal: Circulation (2023)

Introduction: Despite several off-the-shelf ultrasound systems being used for large vessel access, reliable and safe vascular access remains a problem. This is especially true during combat casualty care where skilled operators may not be available. We tested a novel small-footprint platform for efficacy and timeliness of large vessel access at normovolemic and hypovolemic states Hypothesis: A custom-designed device with optimized ergonomics and workflow will yield high success rates and low training needs for large vessel access Methods: Vu-Path has a pen-size 10 mm ultrasound transducer with a proprietary needle guide and a lightweight engine deployed with a tablet or laptop. The display has an overlay showing the needle insertion path. Once the vessel is visible within the overlay, insertion of the needle using the needle guide directs insertion to the vessel. We used 3 models to simulate femoral vessel access: 1) a commercially available phantom (CAE Blue Phantom); 2) a custom in-vitro tissue phantom mimicking swine normovolemic and hypovolemic femoral vascular states; 3) an ex-vivo model of a euthanized swine lower-body section with canulated femoral vessels looped with a peristaltic pump to simulate normovolemic and hypovolemic states. Results: Vu-Path tested in these 3 models resulted in 87% successful insertions across all models and conditions; 100% success on the commercial model versus 83% in the custom tissue phantoms. In every model, 2 metrics were evaluated as summarized in Figure: total time to align vessel in the needle track window, and total time after aligning to confirmed insertion. Mean attempts needed to gain system expertise was 6. Conclusions: Vu-Path had high success rates for vessel visualization and needle access guidance in 3 models simulating normovolemic and hypovolemic conditions. Training requirements were minimal. These data suggest Vu-Path is capable of potentially improving safety and reliability of large vessel access.
Abstract 17056: Hierarchical Clustering of ‘Inflammaging’ Markers Reveals Pro-Inflammatory Cytokines to Associate With Outcome Independent of Chronologic Age After TAVR
Authors: Lukas Zanders, Silvia Mas-Peiro, Alexander Berkowitsch, Lukas Tombor, Tina Rasper, David M Leistner, Stefanie Dimmeler, Andreas M Zeiher
Journal: Circulation (2023)

Background: Aortic valve stenosis (AVS) is an age-related disease lacking effective causal therapies. Aging is linked to cellular senescence, which leads to the secretion of the “senescence-associated secretory phenotype” (SASP). Recent evidence suggests a connection between AVS and SASP expression. Aim: The study aimed to assess expression patterns and the prognostic impact of SASP components in patients undergoing transcatheter valve replacement (TAVR) for severe AVS. Methods: We analyzed 12 SASP components in plasma from 320 patients undergoing TAVR between February 2017 and September 2021, using the Luminex® Assay (Bio-Techne, Germany). Follow-Up was conducted up to 3 years after TAVR with all-cause mortality as the primary endpoint. Hierarchical clustering was performed to identify patterns of SASP expression, and clusters were analyzed for their impact on survival, associations with age and frailty of patients. Significant covariates (p&lt;0.1), as identified by univariate regression, were included in the AFT model for survival analyses. Results: The patients’ median age was 83.2 years (95%CI 82.4 - 83.9), with 39.7% being female. Hierarchical clustering revealed 3 main clusters, characterized by circulating concentrations of pro-inflammatory cytokines (Fig. A). Clusters with higher levels of pro-inflammatory SASP components showed worse survival after adjusting for covariates (COPD, previous stroke, NYHA class, eGFR, anemia) (Fig. B). Patients’ age did not differ between clusters, but those in clusters with higher levels of pro-inflammatory markers were more likely to be frail (Fig. C). Conclusion: In elderly patients undergoing TAVR for severe AVS, pro-inflammatory SASP components are associated with worse survival, independent of chronologic age. These findings suggest a role of cellular senescence and markers of ‘inflammaging’ in outcomes of patients with AVS and might also enhance risk stratification in patients with AVS undergoing TAVR.
Abstract 14368: FAPI-PET Imaging Detects Anthracycline-Induced Cardiotoxicity Before Echocardiography
Authors: Chul-Hee Lee, Luisa Rubinelli, Onorina Manzo, Thomas Jeitner, Sebastian Carrasco, John Babich, Annarita Di Lorenzo, James Kelly
Journal: Circulation (2023)

Introduction: We aimed to validate a PET imaging biomarker for the detection of incipient anthracycline-induced cardiotoxicity. This condition affects &gt;5% of all pediatric cancer patients, leading to long-term health deficits. We hypothesized that fibroblast activation protein (FAP) would be a suitable candidate due to its role in extracellular matrix remodeling and fibrosis during early cardiac injury and the availability of high-affinity PET probes. Methods: Cardiotoxicity was established in male C57BL/6J mice by administering a cumulative 24 mg/kg dose of doxorubicin (DOX) intraperitoneally over 2 weeks [1]. The DOX mice were imaged serially with echocardiography and [68Ga]Ga-FAPI-04 PET over 12 weeks and compared to age- and sex-matched controls. Fractional shortening (FS) was determined from the echocardiograms, and cardiac uptake of [68Ga]Ga-FAPI-04 was quantified and expressed as percent injected dose per cubic centimeter (%ID/cm3). Heart tissue samples were collected and used for the analysis of bulk RNA-seq, RT-qPCR, Western blot, in situ hybridization (ISH), and histological staining. Finally, we used the DAVID tools and STRING database to confirm the relationship between PET signal and gene expression. Results: DOX mice exhibited decreased body weight (33% by 9 weeks after end-of-treatment) and heart weight-to-tibia length ratio (HW/TL, 39%). Cardiac [ 68 Ga]Ga-FAPI-04 PET signal was significantly higher (1.7-fold) in DOX mice from 2 weeks through the study endpoint. By contrast, no cardiac dysfunction was evident by echocardiography until 10 weeks after end-of-treatment, at which point FS was significantly reduced relative to the control group (30%). Transcription and translation of FAP were elevated in the DOX hearts, in agreement with the PET data. In the heatmap generated from the RNA-seq data, genes related to cell adhesion and extracellular remodeling were significantly upregulated in the DOX mice relative to controls. The H-score of FAP ISH was linearly related to the cardiac signal of [ 68 Ga]Ga-FAPI-04 PET (p = 0.001). Conclusions: FAP is a suitable imaging biomarker for cardiotoxicity and FAPI-PET is a promising tool for identifying patients at risk of cardiotoxicity during or after anthracycline chemotherapy.
Abstract 14906: Incidence and Impact of Takotsubo Syndrome in Hospitalized COVID-19 Patients
Authors: Pengyang Li, Ao Shi, Xiaojia Lu, Chenlin Li, Peng CAI, Catherine Teng, Lingling Wu, Qi Liu
Journal: Circulation (2023)

Background: Takotsubo syndrome (TTS) has been reported in coronavirus disease-2019 (COVID-19) patients, although minimal data are available. Objectives: We assessed the incidence and impact of TTS on hospitalized COVID-19 patients. Methods: We conducted a retrospective cohort study using ICD-10 to identify patients with a primary diagnosis of COVID-19 with or without TTS in the National Inpatient Sample 2020 database. We compared outcomes between both groups after propensity score matching for patient and hospital demographics and comorbidities. Results: A total of 211,448 patients with a primary diagnosis of COVID-19 were identified. Of these, 171 (0.08%) had a secondary diagnosis of TTS. Before matching, COVID-19 patients with TTS, compared with those without TTS, were older (68.95 vs 64.26 years) and more likely to be female (64.3% vs 47.2%) and to have anxiety (24.6% vs 12.8), depression (17.5% vs 11.4%), and COPD (24.6% vs 14.7%) (all p&lt;0.05). The TTS group had worse outcomes in death (30.4% vs 11.1%), cardiac arrest (7.6% vs 2.1%), cardiogenic shock (12.9% vs 0.4%), length of stay (LOS, 10.7 vs 7.5 days), and total charges ($152,685 vs $78,468), respectively (all p&lt; 0.001). After matching, the TTS group (n=170), compared with the non-TTS group (n=508), had a higher incidence of inpatient mortality (30% vs 14%, p&lt;0.001), cardiac arrest (7.6% vs 2.8%, p=0.009), and cardiogenic shock (12.4% vs 0.4%, p&lt;0.001), a longer LOS (10.7 vs 7.6 days, p&lt;0.001), and higher total charges ($152,943 vs $79,523, p&lt;0.001). Conclusions: TTS is a rare but severe in-hospital complication in COVID-19 patients.
Abstract 14229: Cost-Effectiveness of a Multicomponent Intervention for Hypertension Control in Public Sector Primary Healthcare Services in Singapore
Authors: Junxing Chay, Tazeen H Jafar, Rebecca Su, Rupesh M Shirore, Ngiap Chuan Tan, Eric A Finkelstein
Journal: Circulation (2023)

Introduction: Recently the SingHypertension cluster-randomized controlled trial investigated integrating a multicomponent intervention (MCI) into Singapore public sector primary care clinics for patients with uncontrolled hypertension. MCI consisted of physician training in risk-based treatment, antihypertensive medication subsidies, nurse-delivered motivational conversations and telephone follow-ups. While MCI improved blood pressure control and cardiovascular disease (CVD) risk scores relative to usual care (UC), the cost-effectiveness of MCI is unknown. Aim: We evaluated the incremental cost-effectiveness of MCI over a ten-year period following the intervention, from Singapore’s health system perspective. Methods: We used a Markov model to simulate the risks and outcomes associated with heart attacks and strokes for a hypothetical cohort of patients based on the trial profile. Costs included MCI administration and oversight, antihypertensive medications, consultations, diagnostics, and hospitalizations. Effectiveness was calculated in terms of disability-adjusted life years (DALYs) averted. Due to differences in outcomes by risk-group, we reported incremental cost effectiveness ratios (ICERs) separately for patients with low and high baseline risk of CVD, as well as an overall ICER. We also assessed the robustness of our results with deterministic and probabilistic sensitivity analyses. Results: Based on a willingness-to-pay threshold of USD 55,600 per DALY, MCI was incrementally cost-effective to UC for both low- (ICER: USD 35,700 per DALY averted) and high-risk patients (ICER: USD 55,500 per DALY averted), with a combined ICER of USD 45,400 per DALY averted. ICERs were most sensitive to the effectiveness of MCI; a reduction in QCVD TM 3 score of at least 0.56 for low-risk patients and 1.00 for high-risk patients was needed for cost-effectiveness. MCI had a 99% and 50% probability of being cost-effective for low- and high-risk patients respectively. Conclusions: MCI is likely cost-effective in reducing the incidence of heart attacks and strokes, especially for lower risk hypertensive patients. Wide-scale implementation of this intervention should be considered to improve blood pressure control in Singapore and beyond.