tbuckley/cabot-search huggingface dataset:
Abstract 12185: Hypoxia Exacerbates Flow-Induced Vascular Remodeling via CXCL12/CXCR4 Pathway
Authors: Tim Klouda, Savas Tsiki, Tiffany Liu, Yunhye Kim, Gary A Visner, Mark Puder, Benjamin Raby, Ke Yuan
Journal: Circulation (2023)

Intro: Patients with congenital heart disease are at risk of developing pulmonary arterial hypertension (PAH-CHD) due to increased blood flow and exposure to hypoxia (Hx). We aimed to establish a“two-hit” mouse model of pulmonary hypertension (PH) combining increased blood flow via left pneumonectomy (LP) and Hx ( Fig 1a ). Our objective was to investigate the pathogenesis of flow-induced vascular remodeling and elucidate the underlying mechanism mediated by smooth muscle cells (SMCs) through the CXCL12/CXCR4 pathway. Hypothesis: We hypothesize SMCs contribute to flow-induced vascular remodeling by upregulating the Cxcl12/Cxcr4 pathway. Methods: Mice underwent LP followed by 3 weeks of Hx(LP/Hx). PH was evaluated by measuring right ventricular systolic pressure (RVSP) and Fulton Index. Whole lung lobes and precision cut lung slices underwent tissue clearing, immunofluorescence staining and advanced microscopy. SMCs were isolated using Dynabeads and Cxcl12 signaling measured by RT-qPCR. Tissue samples from patients with PAH-CHD (ventricular septal defect) were stained for CXCL12. Results: LP/Hx mice demonstrated severe PH compared to Hx controls, as evidenced by increased RVSP (41 vs 33mm Hg), right ventricle hypertrophy (FI: 40 vs 32%) and RV dysfunction ( Fig 1b ). SMCs from LP/Hx mice exhibited an 8.6-fold increase in Cxcl12 expression compared to controls, with Hx and LP alone showing 5-fold and 2-fold increases, respectively. Advanced microscopy revealed excessive remodeling of distal arterioles in LP/Hx mice ( Fig 1c ). Furthermore, CXCL12 expression was upregulated in SMCs of patients with PAH-CHD compared to controls. Conclusion: Our study, using a novel mouse model combining increased blood flow and hypoxia, demonstrated that upregulation of Cxcl12 in SMCs and ECs contributes to flow-induced vascular remodeling. This model has the potential to serve as a pre-clinical model for studying the pathology of PAH-CHD and exploring therapeutic interventions.
Abstract 11661: Genotypic and Phenotypic Guided Antiarrhythmic Drug Management of Multifocal Premature Ventricular Contractions
Authors: Arun Gopi, Hisham Ahamed, Bridget Lee, Arun Mahtani, Jamarcus Brider, Kirollos Gabrah, Brandon Doty, Feross Al-Hindi, Devi Nair
Journal: Circulation (2023)

Introduction: Antiarrhythmic selection for progressive and intractable PVCs unresponsive to first and second line regimens can prove challenging. Genetic analysis assists by targeting specific genes, such as the SCN5a gene, which encodes for the alpha subunit of cardiac sodium channel NaV1.5. Mutations are associated with autosomal dominant phenotypes of multifocal ectopic Purkinje-related premature Contractions (MEPPCs). Case: A 38 year old female with a history of syncope and moderate left ventricular systolic dysfunction status post AICD and a family history of SCD presented for follow-up with complaints of frequent palpitations. ECG and a 72 hour Holter monitor had multifocal PVCs of purkinje origin with a burden of 31%. Despite a therapeutic trial with sotalol and amiodarone in various doses, she remained unresponsive with multifocal purkinje-related PVCs. TTE revealed global LV hypokinesia with worsening LVEF, and a cardiac MRI revealed features suggestive of a dilated cardiomyopathy (DCM) phenotype. Whole exome DNA analysis showed a heterozygous missense mutation pArg814Tryp on exon 16 of the SCN5A gene. Her specific variant, R814W, is a gain-of-function variant responsible for the hyperexcitability of the Purkinje fibers, making it amenable to sodium channel blockade with flecainide. After starting gene-directed flecainide, her PVC burden drastically reduced from 31% to 3% on repeat Holter monitor after 2 months. She has remained asymptomatic with an improved LVEF. Discussion: This is a unique case of SCN5A channelopathy with a MEPPC phenotype demonstrating a dramatic response to genotype guided management of multifocal PVCs. Clinicians should include such phenotypes in their differentials for patients that fail first and second line treatment regimens and have significant family history. It is essential to offer genetic testing to patients with a MEPPC phenotype in a DCM setting to choose the appropriate therapy and prevent SCD.
Abstract 11798: Comparison of Echocardiographic Measurements and Cardiac Biomarkers Between Neonates With Neonatal Encephalopathy Who Developed Brain Injury or Not During Therapeutic Hypothermia
Authors: Anie Lapointe, PIa Wintermark, Emmanouil Rampakakis, Jessica Simoneau, Gabriel Altit
Journal: Circulation (2023)

Background: Despite therapeutic hypothermia (TH), many newborns with neonatal encephalopathy (NE) develop brain injury (BI). We hypothesis that newborns with NE have with brain injury have different echocardiographic (ECHO) parameters to those with no brain injury. Aims: To compare the ECHO parameters on day of life (DOL) 2 between neonates with NE undergoing TH developing or not brain injury. Methods: Prospective cohort study in a single tertiary unit enrolling neonate (born ≥36weeks and ≥1800 grams) undergoing TH for NE, between 2016 and 2020. All neonates presented on admission with moderate to severe NE by amplitude-integrated electroencephalogram (aEEG) profile and underwent a brain magnetic resonance (MRI) on DOL 2. ECHO was performed on the MRI day and data were extracted offline. Multiple logistic regression analyses were constructed to determine which parameters best predicted brain injury or not. Results: A total of 34 neonates were recruited, of which 19 (56%) had brain injury. Those with BI had a higher gestational age (GA) at birth (39.6±1.6 vs 38.2±1.5, p=0.01) and more severe pattern on aEEG (p=0.007) (Table 1). Mortality was also more frequent. Left and right ventricular performance were similar between groups by standard ECHO measures, strain and tissue Doppler imaging (Table 2). Although TAPSE was increased in those with brain injury (p=0.04), the Z-Score accounting for GA was similar. Initial aEEG pattern was the best predictor of brain injury, when accounting for GA and ECHO parameters/biomarkers. Conclusion: Initial aEEG pattern and not hemodynamic profile was most predictive of brain injury on MRI.
Abstract 11787: The Association Between Preoperative Sarcopenia and Outcomes After Cardiac Transplantation
Authors: Elissa Driggin, Alice Chung, Erin Harris, Abraham Bordon, Salwa Rahman, Gabriel T Sayer, Nir Uriel, Koji Takeda, mathew S Maurer, Jay Leb, Kevin Clerkin
Journal: Circulation (2023)

Introduction: Sarcopenia, or reduced muscle mass and function, is underdiagnosed in advanced heart failure and is not routinely assessed. In patients receiving a left ventricular assist device (LVAD), preoperative sarcopenia, defined using CT-derived pectoralis muscle area index (muscle area indexed to height), was an independent predictor of post-operative mortality. The association between preoperative sarcopenia and outcomes after cardiac transplantation is unknown. Aims/Hypotheses: The primary aim was to determine if preoperative sarcopenia, diagnosed using pectoralis muscle area index, is an independent predictor of days alive &amp; out of the hospital at 1-year post-cardiac transplant. We hypothesize that patients with preoperative sarcopenia will have fewer days alive &amp; out of the hospital compared to those without. Methods: Patients who underwent cardiac transplantation from January 2018 to June 2022 with available preoperative chest CT scans (68% of total cohort) were included. Sarcopenia was diagnosed as pectoralis muscle area index in the lowest sex-specific tertile (male &lt; 5.7 cm 2 /m 2 ; female &lt; 4.4 cm 2 /m 2 ). The primary endpoint was days alive &amp; out of the hospital at 1-year post-transplant. Results: 172 patients were included of whom 32.7% met criteria for sarcopenia. Patients with sarcopenia were more likely white with lower body mass index (BMI) (23.5 vs 27.7 kg/m 2 ). Patients with sarcopenia had fewer days alive &amp; out of the hospital compared to those without, with a median difference of 16.5 days (320.5 vs. 337 days, p=0.004). Patients with sarcopenia had a longer index hospitalization (28.5 vs. 22 days) and were more likely to be discharged to a facility other than home (40.4% vs. 12.3%). In a linear regression model, sarcopenia was a significant univariable and the strongest multivariable predictor of days alive &amp; out of the hospital at 1-year when controlling for diabetes status (β = -14.4, 95% CI -28, -1.2, p = 0.032). Conclusions: Preoperative sarcopenia, diagnosed using pectoralis muscle area index, is an independent predictor of poor outcomes after cardiac transplant. This parameter is easily measurable from commonly obtained preoperative CT scans and may be considered in the transplant evaluation as a marker of risk.
Abstract 11676: Use of Natriuretic Peptides and Echocardiography for Diagnosing Heart Failure
Authors: Khawaja M Talha, James L Januzzi, Tong Meng, Stephen J Greene, Muthiah Vaduganathan, Tijana Krnjeta Janicijevic, Ani John, Antoni Bayes-Genis, Javed Butler
Journal: Circulation (2023)

Introduction: International guidelines have recommended the use of echocardiography and natriuretic peptides (NP) in the diagnostic evaluation of heart failure (HF) for more than 10 years. However, real-world utilization of these tests in the US is not known. Objective: To assess contemporary trends in echocardiography and NP testing for diagnosing HF in the US. Methods: The TriNetX data was queried to ascertain the total number of first HF diagnoses in adults aged &gt; 18 in the US from 2016-2019. A random cohort was selected with the following exclusions applied: history of infiltrative or congenital causes of HF, need for heart transplant/ventricular assist device, no healthcare utilization 1 year before diagnosis, fewer than 2 recorded HF diagnoses, and without a valid visit type recorded. NP testing and echocardiography any time before through one year following index diagnosis were assessed. Temporal trend significance was evaluated using Cochran-Armitage trend tests. Findings: A total of 124,126 patients were included in the study. Mean age was 68 + 13 years, 53% were male, and 71% were White. Overall, 61,023 (49%) diagnoses were made in the outpatient and 63,103 (51%) in the inpatient setting with a significantly increasing trend toward inpatient diagnoses (p&lt;0.001; Figure 1A ). Of all incident HF diagnoses, 67,991 (55%) patients underwent NP testing, 70,612 (57%) patients underwent echocardiography, and 31,206 (25%) patients did not undergo either diagnostic test. There were increasing trends in the proportion of patients diagnosed in inpatient vs outpatient among those who underwent NP testing, echocardiography, and either diagnostic test (p&lt;0.001; Figure 1B-D ). Conclusions: We found low rates of echocardiography and NP testing in those with HF, with more such testing performed in patients diagnosed inpatient. We also found increasing rates of inpatient HF diagnoses, indicating lost opportunities for earlier treatment initiation and worse outcomes.
Abstract 11603: Reexamining the Incidence and Predictors of Radiation Induced Cardiac Implantable Electronic Device Malfunction in Cancer Patients and Streamlining Management
Authors: Amit Koduri, Siddharth Chauhan, Martin A Chacon Portillo, Atia Amatullah, Chase Miller, amanda strang, january tsai, shital vachhani, DILIP THAKAR, Julianne Pollard, Stephen Kry, Shalin Shah, Darla Wagner, Donelo Lopez, Juhee Song, Khatera Shah, Cezar Iliescu, Jean-Bernard Durand, Anita Deswal, Kaveh Karimzad
Journal: Circulation (2023)

Background: Historically, the reported incidence of Cardiac Implantable Electronic Device (CIED) malfunction during Radiotherapy (RT) is estimated to range from 3% to 20%. However, most of these studies had small sample sizes and may have overestimated the clinical impact of this problem. In this retrospective study, we examined the incidence of device reset and transient signal interference due to RT in a large cohort of patients. In addition, we studied the feasibility of a novel method of monitoring CIEDs during RT: pulse check method (PCM). Methods: From 1/2015 to 4/2023, patients with CIEDs requiring RT at a tertiary cancer center were identified. CIEDs were checked prior to RT. Candidate patients were managed with PCM, which involves programming the lower pacing rate at 75 bpm (slightly faster than lower rate of pacing during reset mode). Pulse checks were performed after each fraction of RT. Patients with heart rate less than 75 bpm had immediate device interrogation to assess for reset. After completion of RT, devices were interrogated and CIED programming returned to original settings. Results: Our study reviewed 720 patients with CIEDs undergoing 837 courses (560 pacemakers and 277 defibrillators) of RT, of which the majority (85%) were managed with PCM. Neutron producing RT (proton and photon with &gt;10MV beam energy) was used in 189 (22.6%) cases, and 9 (1.1%) devices experienced reset. All resets were recoverable and occurred in the setting of neutron-producing radiation, especially proton therapy [OR 12.06 (3.37 - 43.10), p-value 0.0001]. Site of radiation, type of device, and number of RT fractions did not predict reset. No transient signal interference or oversensing events occurred during RT. Conclusions: CIED malfunction is a rare complication of RT, occurring in the setting of neutron producing radiation, with no serious clinical consequence. Transient signal interference and oversensing during RT was not observed to be a clinical concern in contemporary devices. Thus, asynchronous pacing in pacer dependent patients and deactivation of defibrillator tachy-therapy during RT is not necessary. PCM is a practical and cost-effective way to monitor CIEDs during RT.
Abstract 12170: The Impact of Frailty on Urea Metabolism in Tanushimaru Cohort Study
Authors: Nagisa Morikawa, Mika Enomoto, Ako Fukami, Hiromi Sato, Harumi Yoshimura, Hisashi Adachi, Yoshihiro Fukumoto, Kazuo Takahashi, Kento Kitada, Yuichiro Yano, Akira Nishiyama
Journal: Circulation (2023)

Introduction: Urea metabolism activation, that is urea production, is thought to be very important as a body response for water retention in the process of human evolution. However, it is not clear how that body response is changing as aging. Previous metabolomics studies suggested that various metabolites were influenced by frailty. Thus, we investigated the association between frailty and urea metabolism (urea cycle and TCA cycle) in this study. Methods: We recruited 976 participants who had a health check-up in 2009 and were followed in 2018 in the prospective Tanushimaru cohort study. We defined people with cognitive decline ((≧28 score of Mini-Mental State Examination (MMSE) in 2009 and 24-27 score in 2018), slow gait speed (&lt;1m/s), weaker grip strength (&lt;28kg in men or &lt;18kg in women) in 2018 and weight loss (difference in weight ≧ 4.5kg or 5% of weight in 2009) as “frail-like group”, while those with normal cognitive function in 2009 and 2018 and normal gait speed, grip and no weight loss in 2018 as “control group”. Among them, we extracted 10 age, sex-matched samples randomly from each group and performed targeted metabolomics by the LC/MS/MS Method Package for Primary Metabolites Ver.2 in all 20 serum samples in 2009 and 2018. We compared the activity of the metabolites between the groups and years using t-test and two-way ANOVA. Results: Mean age of 20 samples was 70.2±5.5 years old. According to metabolomics, we found that urea increased significantly in frail-like group than in control group, while other metabolites in urea cycle were not changed. In TCA cycle, Aspartate, Aconitate and Succinate decreased in frail-like group compared to control group (Fig 1). Each metabolite activity was not significantly changed over time. Conclusions: Increased urea was observed in elderly with frailty. Frailty was associated with not urea cycle itself but urea-associated cycle. That may indicate a possibility of the connection of frailty with urea metabolism change.
Abstract 11771: Validity of an Administrative Claims-Based Measure of Low-Value Carotid Revascularization
Authors: Matthew J Navarro, Jessica Han, Michelle Smith, Kelly Wu, Paul N Casale, Vinay Kini
Journal: Circulation (2023)

Introduction: Low value care is defined as care where harms or costs outweigh benefits. Researchers, payers, and policymakers commonly use administrative claims data to identify low-value care, but the validity of many claims-based algorithms has not been assessed. Research Question: What is the validity of a commonly-used claims-based algorithm to identify low-value carotid artery revascularization (CAR) procedures, compared to a reference standard of chart review? Methods: This was a retrospective cohort study of Medicare fee-for-service beneficiaries attributed to a large accountable care organization. We used administrative claims data linked to electronic health record data and identified all CAR procedures (endarterectomy or stenting) from 01/01/2020-12/31/2021. We excluded patients without claims history in the year prior to CAR. Using methods previously described by policymakers and researchers, we classified CAR as low-value by claims if patients did not have diagnosis codes for stroke, transient ischemic attack, or other neurologic symptoms such as vision changes or hemiplegia in the year prior to CAR. We then reviewed linked electronic health records to determine if cases were misclassified by the claims-based measure. Per recent guidelines, we classified CAR as low-value by chart review if it was performed in patients with less than 50% symptomatic stenosis or greater than 80% asymptomatic stenosis. Results: A total of 127 CAR cases (mean age 77 years; 63% men; 87% white) with complete electronic health record data were identified, and 48 (38%) were classified as low-value by the claims-based algorithm. Only 11 of the 48 cases classified as low-value by claims were confirmed to be low-value by chart review. The positive predictive value of the claims-based algorithm was 23%. Conclusions: A commonly-used claims-based measure to identify low-value CAR procedures had poor accuracy with a positive predictive value of 23%. Using administrative claims to identify low-value CAR procedures might overestimate the number of procedures considered to be low-value. This has implications for the current system of quality reporting, particularly when quality is tied to financial incentives.
Abstract 12269: The Association Between Measurements of Obesity and Accelerated Aging Estimated by Artificial Intelligence ECG
Authors: Rosana G Bianchettin, Jose R Medina-Inojosa, Zachi Attia, Betsy Medina-Inojosa, Andrea De Leon, Kathryn Mangold, Mohammad Ali Sheffeh, Lynne Johnson, Paul Friedman, Francisco Lopez-Jimenez
Journal: Circulation (2023)

Introduction: The effect of obesity on physiologic aging has not been completely established. We previously developed an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm that predicts age and determines that the difference between AI-ECG age and chronological age (Age-Gap) may reflect accelerated aging, as it is associated with increased total and cardiovascular (CV) mortality. Hypothesis: Obesity is associated with an increased Age-Gap reflecting morbidity and accelerated aging. Methods: We included adults undergoing a wellness evaluation including, body fat percentage (BF%) determination by air displacement plethysmography (Bod-Pod®) and a 12-lead ECG within 2 years. We excluded those with coronary artery disease, congestive heart failure, stroke or being underweight defined as having a BMI&lt;18.5 kg/m2. Logistic regression models tested the association between obesity by BMI (≥30 kg/m2) or BF% quartiles (≥35% for men and ≥25 in women) and being older by AI-ECG. Results: We included 1295 subjects (70% women), mean chronological age 46.7 ± 13.1 years. Mean Age-gap positive difference compared to those with BMI&lt;25 was 1.39, 2.06 and 2.83 for those with BMI 25-29.9, 30-34.9, and &gt;35 respectively (p&lt;0.05). In the BF% group, Age-gap difference compared to those in the 1st quartile was 0.008, 0.37 and 1.52 for those in the 2nd, 3rd, and 4th quartile (p&lt;0.05). Those&gt;3 years older by ECG were more likely to have obesity by BMI and BF%, see figure. Conclusions: Obesity, either by BMI or BF%, is associated with increased physiologic age as measured by AI-ECG, highlighting the importance of obesity as a health threat.
Abstract 12109: Infective Endocarditis Post-Transcatheter Edge-to-Edge Mitral Valve Repair: A Systematic Review
Authors: Vikash Jaiswal, Muhammad Hanif, Vibhor Agrawal, abhigan babu Shrestha, Mayank Jha, Endurance O Evbayekha, Gayatri Ghadvaje, Jia Ee E Chia, Song Peng Ang, Endurance O Evbayekha
Journal: Circulation (2023)

Background: Infective Endocarditis (IE) post-MitraClip procedure has not been well recognized, with very limited reports published to date. Objective: We aim to systematically evaluate the clinical characteristics, management, outcomes, and prognosis among IE patients after Mitral valve repair with the MitraClip device. Methods: We conducted a systematic literature search in PubMed, Embase, and Scopus from inception till 10th March 2023 by using predefined MESH terms and "AND" and "OR." The following search terms were used: “Infective Endocarditis” AND “Transcatheter mitral valve repair”. Results: A total of 26 publications describing 29 cases of IE following percutaneous edge-to-edge mitral valve repair were identified. The mean age of the patients was 72.62 ± 12.76 years, of which 62.96% were male. The etiology of MR was mostly functional/secondary in 54.55% of cases, while the mean number of implanted clips was 1.65 ± 0.68 (Mode = 1), and the most common location for MitraClip® implantation was the A2-P2 segment. The mean duration from MitraClip® intervention to readmission with IE was 44.44 ± 57.11 weeks. Echocardiography findings showed severe MR in 70.83% of patients. Staphylococcus aureus was the most common infectious organism involved in 56% of cases. Surgical mitral valve replacement with a bioprosthesis was performed in 55.17% of the patients, and 34.48% were managed medically. The most common antibiotic regimen was vancomycin, in addition to rifampicin and gentamycin. Mortality was higher in the medically managed patients as compared to the ones that underwent surgical MVR (40% vs. 37.5%). Conclusion: IE post-TEER of the mitral valve is a rare complication but is associated with a higher mortality rate. Aggressive antibiotic medication and proper prophylaxis during index procedures can be beneficial.