tbuckley/cabot-search huggingface dataset:
Abstract 4146973: Surface Protein Profiling of Extracellular Vesicles: A Novel Biomarker Approach to detect heart allograft acute rejection
Authors: Gentaro Ikeda, Mariko Koike-Ieki, Hiroyuki Inoue, Eileen Tzng, Jiwen Li, Raymond Sierra, Soichi Wakatsuki, Hannah Valantine, Phillip Yang
Journal: Circulation (2024)

Background: After heart transplantation, endomyocardial biopsy is used to monitor for acute rejection (AR). However, endomyocardial biopsy is invasive, and its conventional histological interpretation has limitations. Extracellular vesicles (EVs) are lipid bilayer vesicles secreted by various cell types into the circulation. EVs express an array of biomolecules indicative of their parent cells and act as cargo vesicles capable of delivering nucleic acids, proteins, and organelles. Here, we investigated whether AR affects the surface markers and mitochondrial positivity of plasma EVs and explored their potential for detecting AR in cardiac transplant recipients. Methods: Plasma samples were collected from participants from the Genomic Research Alliance for Transplantation (GRAfT, sponsored by NIH). Histopathology data were collected to define AR. Patients with non-rejection (NR, N=6), acute cellular rejection (ACR, N=7), antibody-mediated rejection (AMR, N=5), and a combination of ACR and AMR (ACR/AMR, N=2) were employed. Plasma EVs were isolated from a total of 71 plasma samples using a size exclusion column (qEV, IZON Science). The size distribution and concentration of the plasma EVs were evaluated by nanoparticle tracking analysis. The positivity for surface markers was assessed by flow cytometry, including CD235a (erythrocytes), CD144 (endothelial cells), CD45 (leukocytes), CD3 (T cells), CD20 (B cells), CD14 (monocytes), and CD172a (cardiomyocytes). Additionally, the positivity for mitochondrial membrane potentials in each EV cluster was measured. Results: The concentrations and mean diameter of the plasma EVs were comparable among NR, AMR, and ACR groups (2.75 x 10 10 /mL, 9.61 x 10 9 /mL, and 2.70 x 10 10 /mL, and 192 nm and 211 nm, and 192 nm, respectively). The proportions of CD45 and CD172a-positive EVs were significantly increased in ACR/AMR compared to ACR or AMR alone. Additionally, mitochondrial markers within CD14-positive EVs exhibited a significant decrease in AMR. No significant trends were observed in the longitudinal EV profiles in each individual. Quantitative PCR confirmed that the expressions of mitochondrial DNA were decreased in the plasma EVs from AMR. Conclusion: CD172a, CD45, and mitochondrial positivity in CD14-positive EVs could serve as potential biomarkers for diagnosing AR in patients undergoing cardiac transplantation. These findings may offer insights into the pathogenesis of AMR.
Abstract Sa502: Early uric acid clearance and survival after out-of-hospital cardiac arrest: A prospective observational study
Authors: Tomoyoshi Tamura, Ryo Yamamoto, Koichiro Homma, Nobuya Kitamura, Tomohisa Nomura, Takashi Tagami, Hideo Yasunaga, Shotaro Aso, Munekazu Takeda, Junichi Sasaki
Journal: Circulation (2024)

Background: Hyperuricemia is frequently seen in patients after cardiac arrest. Persistent hyperuricemia during a cellular energy crisis is believed to result from the breakdown of nucleotides into uric acid (UA) and indicates an insufficient restoration of adenosine triphosphate (ATP) synthesis. Hypothesis: Early reduction in serum UA level, UA clearance (UA-CL), is associated with survival after cardiac arrest. Aims: The study examined the association between UA-CL and 30-day survival following out-of-hospital cardiac arrest (OHCA). Methods: This was a prospective, multicenter, observational study of OHCA cases conducted from 2019 to 2021. The study included adult non-traumatic OHCA patients whose UA levels were measured upon hospital arrival (UA-0h) and 24 hours after cardiac arrest (UA-24h). The proportional change from UA-0h to UA-24h was represented as UA-CL (%). The primary outcome was 30-day survival. An association between UA-CL and 30-day survival was investigated using restricted cubic spline regression and multivariable logistic regression analysis fitted with generalized estimating equations adjusted for patient characteristics, pre-hospital information, resuscitation variables, and within-institution clustering. Results: Among a total of 9,909 OHCA patients, 375 patients were included in the analysis. Compared to the non-survivors (N=166), the survivors (N=209) had more cases of witnessed arrests, bystander CPR, initial shockable rhythms, cardiogenic arrests, and a shorter duration of cardiac arrest. However, there was no difference in UA-0h between survivors and non-survivors (median 7.5 [IQR: 6-9] mg/dL, 7.4 [6-9] mg/dL, respectively; P=0.72). In contrast, UA-CL was significantly higher among the survivors compared to non-survivors (21 [3-42]%, 2.5 [-16-26]%, respectively; P&lt;0.001). Cubic spline curb showed a linear increase in odds for survival with positive UA-CL. Finally, UA-CL was independently associated with 30-day survival after accounting for covariates (adjusted OR 1.01 [1.00-1.02], P=0.04). Conclusion: Regardless of UA-0h level, UA-CL was independently associated with 30-day survival after OHCA. Early UA-CL after cardiac arrest warrants research as an exploitable target to improve outcomes.
Abstract 4147504: Efficacy and Safety of Vorapaxar in Patients with Peripheral Arterial Disease: A Meta-Analysis of Randomized Controlled Trials
Authors: Muhammed Melih Dogan, Lokman Hekim Tanriverdi
Journal: Circulation (2024)

Introduction: Vorapaxar is an inhibitor of protease-activated receptor-1 (PAR1) and primarily blocks thrombin mediated platelet activation. There are discrepancies in the literature regarding whether vorapaxar alleviates ischemic outcomes and increases bleeding in patients with peripheral arterial disease (PAD). Purpose: The aim of this study is to evaluate the efficacy and safety of Vorapaxar in patients with PAD. Methods: A comprehensive literature search of Cochrane CENTRAL, PubMed, Ovid Medline, and Web of Science databases was conducted. Randomized controlled trials (RCTs) comparing Vorapaxar in patients with PAD were included. Primary efficacy outcome was defined as hospitalization for acute limb ischemia, while primary safety outcome was assessed for severe bleeding events according to GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) trial. Summary effect measures of the primary outcomes were obtained by pooling the data with an inverse variance–weighted random-effects model. Statistical analyses were performed with “meta” package in R (version 4.3.2). Results: Three unique RCTs involving 4825 patients were included in the analysis. Vorapaxar was associated with a significantly less rate of hospitalization for acute limb ischemia (Risk Ratio [RR] 0.57, 95% Confidence Interval (CI) 0.39 to 0.83, I 2 : 0%) and significantly less requirement of peripheral revascularization (RR 0.85, 95% CI 0.76 to 0.97, I 2 : 0%) compared to placebo. Furthermore, no significant differences were observed between Vorapaxar and placebo groups in fatal bleeding (RR 1.00, 95% CI 0.38 to 2.66, I 2 : 0), severe bleeding according to GUSTO trial (RR 1.38, 95% CI 0.84 to 2.27, I 2 : 0%), and lower extremity amputation (RR 0.53, 95% CI 0.17 to 1.67, I 2 : 0%). Conclusion: In patients with PAD, Vorapaxar significantly reduces hospitalizations due to acute limb ischemia and the need for peripheral revascularizations compared to placebo. However, it does not have a significant effect on the need for lower extremity amputations. In terms of safety, Vorapaxar does not lead to fatal or severe bleedings compared to placebo. Therefore, Vorapaxar should remain one of the treatment options for patients with PAD.
Abstract 4147083: Incidental and progressive tobacco smoking from childhood through young adulthood with premature structural and functional cardiac damage in 1931 children: A 14-Year Longitudinal Study
Authors: Andrew Agbaje
Journal: Circulation (2024)

Background: Tobacco smoking in adolescence has been associated with increased risk of premature death in mid-forties. However, due to the scarcity of repeated measures of cardiac structure and function in a large cohort of children and adolescents, there is limited knowledge regarding the independent associations of initiating and progressive tobacco smoking with premature cardiac damage in apparently healthy youth. The earliest manifestation of the cardiovascular consequence of tobacco smoking is critical for public health intervention and preventive cardiology. Purpose: To investigate the incidence of tobacco smoking during growth from childhood through young adulthood and the longitudinal association of tobacco smoking with structural and functional cardiac damage. Methods: From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1931 children had questionnaire-based smoking status assessed at ages 10, 13, 15, 17 and 24 years clinic visits were included. Repeated echocardiography measured left ventricular mass indexed for height 2.7 (LVMI 2.7 ), relative wall thickness (RWT), LV diastolic function from mitral E/A ratio (LVDF), and LV filling pressure from E/e ratio (LVFP) were available at ages 17 and 24 years. LVMI 2.7 ≥51g/m 2.7 , RWT ≥0.44, LVDF&lt;1.5, and LVFP ≥8 were categorised as LV hypertrophy, high RWT, LVD dysfunction, and high LVFP, respectively. Results: Among 1931 children (mean [SD] age at baseline was 10.6 [0.26] years; 1211 [62.7%] females]) the prevalence of smoking was 0.3%, 1.6%, 13.6%, 24%, and 26.4% at ages 10, 13, 15, 17, and 24 years, respectively. The prevalence of LV hypertrophy increased from 2.8% to 7.5% at age 24 years while LVD dysfunction prevalence increased from 10.4% to 16.9%. In a fully adjusted model, persistent smoking from childhood through young adulthood was significantly associated with higher odds of LV hypertrophy (odds ratio 1.52; [95% CI, 1.39 – 1.66], p&lt;0.001), high RWT (1.38; [1.26 – 1.51], p&lt;0.001), LVD dysfunction (1.33; [1.22 – 1.46], p&lt;0.001), and high LVFP (1.35; [1.25 – 1.45], p&lt;0.001) at age 24 years. Persistent smoking from childhood contributed 0.46g/m 2.7 (0.17 – 0.75) of 2.84g/m 2.7 increase in LVMI from ages 17 – 24 years. Conclusion: Tobacco smoking from childhood through young adulthood was prospectively associated with structural and functional cardiac damage and contributed 16% to cardiac mass increase between ages 17 to 24 years.
Abstract 4147484: Association Between Protein Energy Malnutrition and Transplant Rejection in the Heart Transplant Population. A Retrospective Inpatient Database Analysis
Authors: Endurance Evbayekha, EUGENE OMOIKE, Gabriel Alugba, jayadev sajja, Uthman Younis, CRAIG REISS
Journal: Circulation (2024)

Introduction: Heart transplant (HT) is the gold standard for advanced heart failure, and the individuals burdened by advanced heart failure often have multiple comorbidities. Protein-energy malnutrition (PEM) is a common comorbidity and is frequently underdiagnosed. Previous studies examined the relationship between PEM and mortality in HT and found a positive association. However, the relationship between PEM and HT rejection, HT failure, and cardiac allograft vasculopathy (CAV) is scarce. Given that these complications also impact survival, we sought to explore the relationship. Methods: We identified all HT patients using ICD-10 codes from the 2016 to 2021 National Inpatient Sample database. Then, the PEM group was compared to the no-PEM group. We used Student’s Test and Pearson’s Chi-squared to analyze continuous and categorical variables. Then, multivariable logistic regression models were used to account for confounders and to predict the outcomes. The primary outcomes were HT rejection, HT failure, and CAV. The secondary outcomes were mortality, arrhythmias (composite of atrial and ventricular fibrillation and flutter, and supraventricular tachycardia), length of hospital stay, and cost of hospitalization. A 2-sided p-value was the statistical threshold for significance. Results: During the study period, 31,215 HT hospitalizations occurred, and 11.9% (3,700) had PEM. The median age for the PEM group was 65 years. Compared to the no-PEM group, HT rejection 0.8 (0.4-1.5), HT failure 0.8 (0.3-2.1), and CAV 1.08 (0.6-1.9) did not differ between both groups, p&gt;0.05, each. The PEM group had a higher association with mortality 2.8 (2.1-3.6), arrhythmias 1.4 (1.07-1.8), longer LOS 8 vs. 4 days, and higher cost of hospitalization, $84,687 vs. $43,285, p&lt;0.01 each. Conclusion: Among the heart transplant population, protein-energy malnutrition was not associated with transplant rejection, transplant failure, or CAV. However, protein-energy malnutrition was associated with mortality, arrhythmias, a longer hospital stay, and a higher cost of hospitalization.
Abstract Sa307: Head and Thorax Elevation Cardiopulmonary Resuscitation versus Flat Cardiopulmonary Resuscitation with Extracorporeal Membrane Oxygenation as Salvage Therapy in a Severe Porcine Model of Cardiac Arrest
Authors: Johanna Moore, Pouria Pourzand, Bayert Salverda, Mithun Suresh, Michael Lick, Hamza Hai, Bailey Kent, Anja Metzger, Keith Lurie
Journal: Circulation (2024)

Background: Elevation of the head and thorax (HUP) in combination with active compression decompression (ACD) cardiopulmonary resuscitation (CPR) and an impedance threshold device (ITD) is starting to be used clinically by first responders. Extracorporeal membrane oxygenation in cardiac arrest (ECPR) for refractory cardiac arrest is also increasingly used and evolving. The potential benefit of ACD+ITD HUP CPR with ECPR is unclear. Aim: Demonstrate superior incidence of survival with ACD+ITD HUP CPR versus ACD+ITD CPR flat in an animal model that includes salvage with ECPR. Methods: Female and male Yorkshire-hybrid swine (~40 kg) were sedated and anesthetized. After intubation, bilateral percutaneous venous and arterial access were obtained. High fidelity micromanometer pressure transducers were used to measure arterial and venous pressures. Regional cerebral tissue oxygenation (rSO2) was also continuously monitored. Ventricular fibrillation was induced and left untreated for 15 minutes. During this time, animals were randomized to 1) HUP CPR or 2) flat CPR, and ACD+ITD CPR in both groups was then performed for 45 minutes. At 44 minutes, epinephrine and amiodarone were given and defibrillation attempted up to 3 times. If return of spontaneous circulation (ROSC) was not obtained, ECPR was then performed and continued for up to 6 hours. Neurological assessment was performed at 24 hours post arrest by a veterinarian blinded to the intervention. A Fisher’s exact test was used to compare outcomes between groups and an unpaired t-test for continuous data. Results: In this ongoing study (n=17), 8 animals were randomized to HUP and 9 to flat. After 44 minutes of CPR, mean ± SD rSO2 (%) was 63 ± 7.7 for the HUP group and 54.7 ± 6.6 for the flat group (p = 0.04). ROSC was achieved in 4/8 (50%) in the HUP group and 4/9 (44%) in the flat group (p = 1.0). ECPR was performed in 3/8 (37.5%) in the HUP group and 5/9 (56%) in the flat group (p = 0.64). Most animals (7/8, 88%) had ECPR performed successfully. ROSC was not obtained and ECPR deemed futile in one HUP animal. At 24 hours, 3/8 (37.5%) of the HUP animals and 0/9 (0%) of the flat animals survived (p= 0.08). One HUP animal (12.5%) survived without any neurologic deficit. None of the animals that required ECPR survived to 24 hours. Conclusions: In this severe model of cardiac arrest, a small number of animals survived, all of them receiving ACD+ITD HUP CPR and did not require ECPR.
Abstract 4147505: A RETROSPECTIVE EVALUATION OF RESOURCE UTILIZATION AND OUTCOMES IN PATIENTS USING MOBILE ECG DEVICES FOLLOWING ABLATION FOR ATRIAL FIBRILLATION
Authors: Alix Fairman, Alexander Loh, Lauren Druml, Cynthia Triplett, Taylor Liu, Seema Pursnani
Journal: Circulation (2024)

Background: Mobile electrocardiogram (mECG) algorithms have been validated for early detection of atrial fibrillation (AF), with a potential for reduced arrhythmia-related healthcare utilization. In this study, we compare healthcare utilization metrics of mECG and non-mECG users who previously underwent AF ablation to provide insights about resource utilization during the COVID 19 pandemic. Methods: This is a retrospective study of patients with known AF who underwent ablation in 2020. We identified patients as having an mECG device through chart review of the electronic health record. Baseline demographic, clinical, and procedural characteristics were collected in addition to resource utilization outcomes 1-year pre- and post-ablation. COHORT: There were 322 patients who met study criteria, with n=144 being mECG users and n=178 being non-mECG users. The mECG and non-mECG user groups were comparable by age, sex, race, and clinical/echocardiographic factors (Table 1). There was a greater proportion of persistent AF in the non-mECG user group. Results: mECG users sent a significantly larger number of secure messages to their providers in both the pre- and post-ablation period (Figure 1). There were no statistically significant differences in outpatient provider visits, ED visits, or hospitalizations (Table 2). Success rates of ablation were comparable in both groups. Discussion: mECG users, compared to non-mECG users, sent more secure messages to providers both pre and post ablation, but mECG users did not have a reduction in provider, ED or hospital visits at 1 year post AF ablation. Given that utilization of a mECG device increased the number of communications with providers, more work should be done to develop workflows for clinicians to triage, manage and integrate mobile ECG data into clinical practice. Key Takeaways: Mobile ECG users sent significantly more messages to providers, without a reduction in provider, ED, or hospital visits. Integration of wearable device data into clinical care requires further understanding on the provider specific and systemic impacts on resource utilization.
Abstract 4146814: Heart failure is time-dependent and associated with heart transplant, hepatocellular carcinoma, and death in the Fontan population
Authors: Lindsey Ivey, Cheryl Raskind-Hood, Alexandra Haffner, Yuting Guo, ABEED SARKER, Fred Rodriguez, Wendy Book
Journal: Circulation (2024)

Background: The Fontan operation has been an effective treatment plan for patients with single ventricle anomalies, greatly improving survival into adulthood. Yet, Fontan patients are at increased risk of numerous cardiac and noncardiac complications, and premature mortality. Methods: A cohort of 735 patients with a prior Fontan surgery (median age 7.6yrs at first encounter, 57.4% male, 41.0% Black), with at least one healthcare encounter from a pediatric or adult healthcare system between 2010-2019, was linked to encounter data and death certificates. Heart failure (HF) was defined by ICD-9-CM and ICD-10-CM codes determined by clinicians. The primary composite outcome included heart transplant, hepatocellular carcinoma (HCC) and death. Hospitalizations were defined as an inpatient encounter spanning at least two consecutive days. Time to event was anchored at initial encounter. Results: Characteristics of those with and without HF are seen in Table 1. Median age was 17.1yrs [3.0-70.5] and 5.5yrs [3.0-56.0] for those with and without HF, respectively. The composite outcome occurred in 85 Fontan patients (11.6%) at median 3.26yrs after initial encounter. Of those with HF, 12.5% experienced a heart transplant compared to 0.9% without HF (p&lt;0.001), 3.0% with HF had HCC vs 0.5% without HF (p&lt;0.05), and 9.4% with HF died at mean age 29.3yrs compared to 2.7% without HF at mean age 16.3yrs (p&lt;0.001). Kaplan-Meier event-free survival curves appear in Figure 1. Of those with HF, 69.0% were hospitalized at least once compared to 53.0% of those without HF (p&lt;0.001). Fontan patients without HF were 95.9% likely to be event-free at 5yrs follow-up compared to those with HF who were 84.7% likely to be event-free at 5yrs. Conclusion: Fontan patients more commonly experience HF at older ages. HF is associated with heart transplant, HCC, and death during follow-up compared with Fontan patients without HF. Hospitalizations were common in both groups, but occurred more commonly with HF.
Abstract 4147067: Acute Exposure to High PM <sub>2.5</sub> Levels Increases the Risk of Late All-Cause Mortality in Patients with STEMI
Authors: Sina Fathieh, Hao Tran, Amir Faour, Reece Pahn, Mitchell Long, Gladys Tam, Gemma Figtree, Kazuaki Negishi, John French
Journal: Circulation (2024)

Background: Short-term exposure to ambient air pollution, especially particulate matter smaller than 2.5 microns in diameter (PM 2.5 ), is associated with an increased risk of acute coronary syndrome and is identified as the leading modifiable cause of cardiovascular mortality in the long term. In this study, we set out to examine the effect of acute exposure to high levels of PM 2.5 (≥12 μg/m 3 ) on long-term mortality risk of ST-elevation myocardial infarction (STEMI) patients. Methods: From June 2010 to October 2021, 1,553 patients at Liverpool Hospital in Sydney met the 4th Universal Definition of MI criteria for STEMI. The average daily maximum PM 2.5 was measured using publicly available land-based air quality monitors in the catchment area. Mortality risk between the two groups was compared using a Kaplan-Meier plot and further assessed using the Cox regression model. Results: 915 STEMI patients presented on days with maximum PM 2.5 ≥12 μg/m 3 . These patients had a significantly increased risk of late all-cause mortality with a hazard ratio of 3.08 (CI= 2.01-4.71, p&lt;0.001) compared with those with lower PM 2.5 level exposures. Each 10-unit increase in PM 2.5 exposure was associated with a 10% (p=0.002) higher risk of late mortality. Conclusions: Patients presenting with STEMI on polluted days are at increased risk of late all-cause mortality, which may be due to increased inflammatory response and myocardial injury at the time of cardiac insult. This finding warrants a more diligent acute care and long-term follow-up strategy for this group of vulnerable patients.