tbuckley/cabot-search huggingface dataset:
Abstract 4145829: Fatty Acid Binding Protein 4 as Potential Indicator for Gestational Diabetes Mellitus-Induced Fetal Endothelial Dysfunction
Authors: Maria de Leyre Villar Ballesteros, Heike Brendel, Clara Hengst, Philine Sophie Carstens, Deborah Effenberger, Jennifer Mittag, Sindy Giebe, Alexander Fruehauf, Cahit Birdir, Paul Taylor, Henning Morawietz
Journal: Circulation (2024)

Introduction/Background: Gestational diabetes mellitus (GDM) is the most common complication during pregnancy. GDM is leading to an elevated risk for the development of cardiovascular diseases both in the mother and the child in later life. Previous studies have identified fatty acid-binding protein 4 (FABP4) as a prime candidate involved in the pathophysiology of GDM. Indeed, women with GDM exhibit elevated blood levels of FABP4, suggesting its potential role as a biomarker for endothelial dysfunction and cardiovascular risk assessment in GDM. Research Question/Hypothesis: Does FABP4 affect the function of human endothelial cells from patients with GDM? Goals/Aim: Our aim is a better understanding of the role of FABP4 in fetal endothelial dysfunction of patients with GDM and the development of potential therapeutic strategies. Methods/Approach: Primary human umbilical vein endothelial cells (HUVECs) were isolated from umbilical cords obtained from normoglycemic and GDM pregnancies. Total mRNA from HUVECs was used for bulk RNA sequencing to compare gene expression pattern. HUVECs were subjected to functional analyses assessing proliferation, migration, NO and insulin signaling. Finally, human endothelial cells were exposed to high laminar flow (30 dyn/cm 2 ) or simvastatin (10 nM) treatment to investigate their impact on FABP4 expression and endothelial function. Results/Data: Bulk RNA sequencing data analysis revealed FABP4 as a gene overexpressed in GDM HUVECs compared to normoglycemic controls. Gene set enrichment analysis showed in addition an enrichment of genes involved in angiogenesis and Notch signaling pathways in human endothelial cells from GDM patients. GDM HUVECs had a significantly higher wound healing capacity compared to normoglycemic controls. The PI3K/AKT/mTOR pathway was enriched in GDM HUVECs. GDM HUVECs displayed impaired activation of AKT and eNOS (expression and phosphorylation) after stimulation with insulin, suggesting a possible insulin resistance. Finally, subjecting HUVECs to high laminar shear stress or simvastatin treatment caused a reduction of FABP4 mRNA expression and an increase of eNOS expression, indicating potential therapeutic strategies to improve endothelial function. Conclusions: We provided evidence that FABP4 could be involved in fetal GDM-induced endothelial dysfunction. High laminar shear stress and medications activating eNOS signaling could protect the endothelium against the negative impact of FABP4 in GDM.
Abstract 4144542: In-Hospital Outcomes of Open Mitral Valve Repair or Replacement versus Percutaneous Mitral Valve Repair or Replacement in patients with Prior Mediastinal Radiation: Insight from The National Inpatient Database (2015-2020)
Authors: Muhammad Osama, Nauman Naeem, asmaa ahmed, Muhammad Ahmad, Saif ur Rehman, Muhammad Hammad Sharif, Mallory Balmer-Swain
Journal: Circulation (2024)

Background: Radiation associated heart disease has a wide spectrum of manifestations including pericardial disease, coronary artery disease, and valvular heart disease. Mitral valve regurgitation is the second most common valvular dysfunction in patients with prior mediastinal radiation. Research Question: What are the outcomes of percutaneous or transcatheter mitral valve replacement/repair (T-MVR) versus surgical mitral valve replacement/repair (S-MVR) in patients with prior mediastinal radiation. Methods: The National Inpatient Sample (NIS) was analyzed from 2015-2020 to identify patients with mediastinal tumors and prior exposure to radiation therapy undergoing mitral valve repair/replacement. We subclassified the data into hospitalizations for S-MVR and T-MVR. Baseline characteristics were compared between the two groups and multivariate logistic regression was used to analyze hospitalization outcomes. Results: A total of 1725 patients with prior mediastinal radiation were hospitalized for MVR; 1110 (64.3%) patients underwent S-MVR and 615 (35.6%) patients underwent T-MVR. On a multivariable analysis, the odds of MACCE [aOR: 2.21; 95 % CI: (1.87-4.01); p &lt;0.001)], and in-hospital mortality [aOR: 5.6; 95% CI (2.06-7.35); p=0.008] were higher in patients undergoing S-MVR compared to those undergoing T-MVR. Additionally, patients undergoing S-MVR had higher odds of periprocedural complications including cardiogenic shock [aOR: 7.4; 95% CI: (3.75 -9.20); p &lt;0.001], major bleeding [aOR: 2.9; 95% CI: (1.26-7.09); p=0.01], AKI [aOR: 3.4; 95% CI: (1.33-5.23); p &lt;0.001], stroke [aOR: 5.01; 95% CI: (1.51-6.57); p=0.008], and MCS utilization [aOR: 3.05; 95% CI: (1.31-7.13); p=0.009] compared to the T-MVR cohort. Conclusion: Compared to T-MVR, S-MVR was associated with higher odds of MACCE, in-hospital mortality and periprocedural complications suggesting that T-MVR might be a safer option for MVR among patients with prior mediastinal radiation.
Abstract 4145821: Serial Vascular Responses of Balloon-expandable Stent with Biodegradable Film-type Graft in a Rabbit Iliac Artery Dissection Model (BioGard Study)
Authors: Sang Min Park
Journal: Circulation (2024)

Introduction and Background: Arterial dissection during endovascular therapy rarely occurs but can be lethal. A significant blood volume extravasation during coronary artery interventions is related to the very high mortality (20-30%). In this hyperacute emergent clinical situation, covered stents have been considered as a primary measure to prevent further serious arterial events. A fabric-based covered graft stents yield poor clinical outcomes. To overcome these challenges, the balloon-expandable stent with biodegradable film-type graft for treating arterial dissection was invented. Research Questions and Objectives: A novel balloon-expandable stent with biodegradable film graft for overcoming these issues would be valid for efficacy and safety in a rabbit iliac artery dissection model. Method and Approach: Eighteen iliac artery dissections were induced by balloon over-inflation on angiography (Ellis type 2 or 3) and treated using the test device (3.0 x 24 mm). Subsequently, twelve animals underwent histologic examinations and micro-computed tomography (CT) at 0, 2, 4, and 8 weeks and 3, 6, 9, and 12 months and angiography at one-year. Results and Data: There were no adverse cardiovascular events during the one-year. Early-stage histologic examination revealed complete sealing of disrupted vessels by the device, exhibiting mural hematoma, peri-stent red thrombi, and dense infiltration of inflammatory cells. Mid- and long-term histologic examination showed patent stents with neointimal hyperplasia over the stents (% area stenosis: 11.8 at 2weeks, 26.1 at 1month, 29.7 at 3months, 49.2 at 9months, and 51.0 at 1year), along with mild peri-strut inflammatory response (Grade: 1-2 at mid-term and 0-1 at long-term). The graft film became scarcely visible after six months. Both CT and angiography revealed no instances of thrombotic occlusion or in-stent restenosis (% diameter stenosis: 5.7 at 2weeks, 12.3 at 1month, 14.2 at 3months, 25.1 at 9months, and 26.6 at 1 year). Conclusion: The novel balloon-expandable stent with a biodegradable film graft demonstrates feasibility in managing severe artery dissection and preventing lethal vascular events in animal model. Future human studies are warranted to validate these findings and elucidate the clinical outcomes of the study.
Abstract 4140136: Aortic Valve Calcification Density Performs Better Compared to Absolute Aortic Valve Calcification in Aortic Stenosis Risk Stratification
Authors: Syed Ahmad, HangYu Watson, Maan Awad, Kunal Patel, Sameh Nassar, Harshith Thyagaturu, Sudarshan Balla, Mohammad Kawsara, Ramesh Daggubati, Irfan Zeb
Journal: Circulation (2024)

Aortic valve calcification (AVC) scores can be used to stratify aortic stenosis (AS) severity. Current practice guidelines recommend use of absolute AVC scores without considering body surface area or aortic annulus size. We investigated whether size variation in aortic annular area should be considered in identifying optimal AVC cutoffs for patients with severe AS. This was a retrospective analysis of AS patients that underwent AVC assessment during 2018-2023. Outcomes were composite of valve intervention or all-cause mortality. AVC density was defined by dividing AVC by echo-derived left ventricular tract area. Receiver operator curve analysis determined optimal AVC density scores. Absolute AVC cutoffs of &gt;1200AU for females and &gt;2000AU for males were used to identify severe AS. The study included 749 patients (mean age 78 years, 46% female). Median CT-annulus area was larger for males compared with females (532mm 2 [Q1, Q3: 479, 582] vs. 413mm 2 [370, 458], p&lt;0.001). There was a strong association of absolute AVC with CT-annulus area for both males and females (Spearman coefficient: 0.87 and 0.83, p&lt;0.01 each) respectively (Figure 1). The optimal AVC density cutoffs for males and females were 427 and 326, respectively (accuracy 76%, sensitivity 83%, specificity 51%). Composite outcomes were better differentiated with AVC density (males: HR 2.48, 95% CI: 1.82-3.37, p&lt;0.001; females: HR 2.37 (1.71-3.28), p&lt;0.001) compared with absolute AVC scores (males: HR 1.81 (1.43-2.30), p&lt;0.001; females: HR 2.11 (1.62-2.74), p&lt;0.001) (Figure 2). AVC is strongly associated with CT-annulus area and risk stratification is improved with the use of AVC density compared with absolute AVC. This may be especially helpful in patients with extremes of annulus area sizes.
Abstract 4146301: Relationship Between Calf Muscle Pump Function and Exercise Stress Testing
Authors: Atefeh Ghorbanzadeh, Robert McBane, David Liedl, Amanda Bonikowske, Max Guarda, Damon Houghton
Journal: Circulation (2024)

Background: Exercise stress testing uses metabolic equivalents of tasks (METs) to measure the energy cost of activities, aiding in the assessment of exercise capacity and cardiovascular health. Despite its significance, the correlation between calf muscle pump function (CPF) and exercise stress testing remains unexplored. We aimed to evaluate the relationship between CPF and peak METs as determined by cardiopulmonary treadmill exercise stress testing. Methods: The study included adults who underwent exercise cardiopulmonary stress testing and venous plethysmography at Mayo Clinic between April 2017 and March 2020. The protocols other than Bruce, Mayo, Modified Naughton, and Naughton protocols were excluded. The CPF ejection fraction (EF) was calculated per leg based on refill volumes post-exercise as a percentage of passive drain refill. The classification of CEAP (Clinical-Etiology-Anatomy-Pathophysiology) was utilized to better understand chronic venous insufficiency (CVI). Results: A total of 155 patients who underwent both exercise stress testing and venous plethysmography were included, with a mean age of 61.31 ± 14.03 years, and 84 (54.2%) were male. The peak measured METs for normal, unilaterally reduced, and bilaterally reduced CPF were 8.5 (2.5), 7.3 (2.1), and 7.1 (2.4), respectively (p=0.004, Figure 1). Multiple linear regression models were developed with METs as the outcome to determine if CPF was an independent predictor of METs on cardiopulmonary exercise stress testing. IIn model 1, the following independent variables were included: resting heart rate, peak heart rate, peak systolic blood pressure, recovery heart rate at minute 1, and worst EF (Table 1). In model 1, with only exercise parameters, lower EF was associated with lower METs (p=0.03). In a second analysis, variables identified as statistically significant with METs in the initial model were included, along with CEAP class (model 2) and CCI (model 3) (Table 2). In model 2, CEAP class 3 or higher was associated with decreased METs on the exercise stress test. This correlation implies that individuals with moderate to severe CVI may influence exercise capacity, demonstrating the interconnectedness of the cardiovascular system. Moreover, in model 3, the CCI, a predictor for mortality, was not significantly associated with METs. Conclusion: Our findings revealed that more severe CVI (CEAP class and reduced CPF) was associated with reduced exercise capacity after accounting for other factors.
Abstract Sa1105: The Effect of a Combination of Neuroprotective Medications on Post-Cardiac Arrest Survival
Authors: Kenna Pollard, Anelly Gonzales, Yulan Ren, Natalia Leontovich, Samantha Shellen, Andy Chen, Imani Goins, Nancy Amoroso, Wendy Wise, David Kaufman, David Fridman, Pedro Rivera, Jacklyn Hagedorn, Shari Brosnahan, John Papadopoulos, Alyson Katz, Elyse LaFond, Anthony Andriotis, jan bakker, Ronald Goldenberg, Anthony Lubinsky, Deepak Pradhan, James Horowitz, Karsten Drus, Sam Parnia
Journal: Circulation (2024)

Introduction: Reperfusion injury after cardiac arrest (CA) leads to poor survival and neurological outcomes. We hypothesized that a combination of pharmacologic neuroprotection therapies administered 24-72 hours post-CA [“combination therapy”] that target key steps in reperfusion injury; 1) excitotoxicity (Magnesium, Memantine, Perampanel, Minocycline), 2) mitochondrial dysfunction (Thiamine, Coenzyme Q10), 3) oxidative stress (Vitamin C, Vitamin E), and 4) inflammation (Hydrocortisone), would improve survival. AIMS: We compared survival between subjects with combination therapy and those without. Methods: A retrospective analysis of post-CA patients (01/01/2019 - 06/01/2023) was conducted as part of a quality improvement project. Inclusion: in-hospital CA, age ≥ 18 years, non-COVID, ≥ 5 min CPR, sustained ROSC (≥ 20 min). Exclusion: out-of-hospital CA. Combination therapy was at the discretion of the provider and given in addition to current post-CA standard critical care: targeted temperature management (TTM) (32-36°C), glucose (target 140 mg/dL), PaO2 (target 100 mmHg), PaCO2 (target 40 mmHg), and MAP (target 80 - 100 mmHg). Survival was assessed at hospital discharge. Results: Among 196 subjects, 146 received combination therapy (study group) and 50 did not (control group). Demographic variables (age, race, ethnicity) and intra-cardiac arrest variables (initial rhythm, CPR duration, and hospital site) were not statistically different between groups. Post-CA variables (mean PaCO2, PaO2, and glucose) were not statistically different between groups. MAP was 76 (69, 83) for study group and 65 (46, 72) for control group ( P = &lt;0.001). Lowest temperature in study group was 34.8°C vs. 35.9°C in control group ( P = 0.034). Survival at hospital discharge was 33% for study group and 14% for control group ( P = 0.01). There were no known safety concerns or adverse events. Conclusions: The administration of a combination of neuroprotective medications that target key pathways in reperfusion injury appears to be feasible and safe, and may improve survival beyond current post-CA standard critical care. A future randomized controlled trial that includes the assessment of neurological outcomes is warranted.
Abstract 4133846: Even Mild Increase in Pulmonary Arterial Pressure Following Kidney Transplantation is Associated with Increased Mortality
Authors: Katarina Zeder, Suman Kundu, edward siew, Kelly Birdwell, Matthew Freiberg, Gabor Kovacs, Evan Brittain, Brad Maron
Journal: Circulation (2024)

Background: In end-stage renal disease (ESRD), elevated systolic pulmonary artery pressure (sPAP) is common, attributed to post-capillary pulmonary hypertension (PH) and associated with adverse outcomes. Kidney transplantation (KT) may mitigate ESRD-PH. We aimed to profile sPAP trajectory in a national cohort of ESRD patients pre- and post-KT, and link findings to clinical outcome. Methods: We analyzed retrospectively all patients within the Veterans Affairs Healthcare System undergoing KT between 2000-2019 with sPAP recorded pre- and post-KT by echocardiography. PH was defined by &gt;35mmHg. Patients were assigned to one of the following groups: Never PH, New PH post-KT, Resolved PH post-KT, and Persistent PH. Spline curve and Kaplan-Meier analyses were used to test the association of sPAP or PH group with all-cause mortality, adjusted for age and sex. Results: From 631 patients (median 62 [IQR 58-65]yr; 97% male), there were 231 (36.6%), 184 (29.2%), 133 (21.1%), and 83 (13.1%) patients in the Persistent PH, Never PH, Resolved PH, and New PH groups, respectively. Never PH, Resolved PH and New PH had, overall, similar cardiopulmonary comorbidities ( Tab. 1 ). By contrast, Persistent PH had the highest rate of congestive heart failure, atrial fibrillation, and impaired diastolic relaxation assessed by E/E’. Creatinine post-KT, indicative for graft function, was stable in Never PH, Resolved PH and Persistent PH, but significantly increased in New PH. Of all groups, Resolved PH was associated with the most favorable survival rate (HR 0.73 [95%CI 0.51-1.05], p=0.087). New PH and Persistent PH were associated with a 51% (HR=1.51 [95%CI 1.06-2.15], p=0.023) and 37% (HR=1.37 [95%CI 1.03-1.82], p=0.029; referent group for all: Never PH) increase in adjusted mortality risk post-KT ( Fig. 1a ). Overall, we observed 21% (HR=1.21 [95%CI 1.11-1.31], p&lt;0.001) increase in mortality hazard adjusted for age, sex and baseline sPAP, per 10mmHg increment increase in sPAP from pre-KT to post-KT whereas a 10mmHg sPAP decrease was associated a 17% decrease in mortality (HR=0.83 [95%CI 0.76-0.90], p&lt;0.001) ( Fig. 1b ). Conclusion: These data suggest that PH is common post-KT and includes a sizeable group of patients without PH pre-KT. Increased PAP or failure for PH to resolve post-KT were independently associated with mortality. Overall, these data warrant prospective studies in sex-balanced cohorts that use PH to stratify KT candidacy and PAP as a longitudinal biomarker of graft function post-KT.
Abstract 4144574: Cardiovascular Risk in Cancer Survivor Patients: A Systematic Review and Meta-analysis of 1.2 Million Cancer Survivors.
Authors: Abhigan Shrestha, Sajina Shrestha, Sulochana Khadka, Anirudra Devkota, ANIL KC, Aman Goyal, Suman Kadariya, Vikash Jaiswal
Journal: Circulation (2024)

Background: According to the American Cancer Society, there are currently over 18 million adult cancer survivors in the US, and by 2030, that figure is estimated to rise to over 22 million. While this is positive, more and more survivors are now at risk for cardiovascular disease (CVD). Hypothesis: This meta-analysis aims to evaluate the association between cancer survivors and cardiovascular event. Methods: A systematic search was conducted in electronic databases from inception until March 2024 using appropriate Mesh terms for ‘Cancer’, and ‘cardiovascular risk’. Pooled risk ratios (RR) with their corresponding 95% confidence intervals (CI) were calculated using random effects models. A p-value of &lt;0.05 was considered statistically significant. Results: A total of nine studies with 1,209,168 people (Cancer survivor: 140697 and non-cancer: 1068471) were included in our study. The mean follow-up duration was 12.4 years. The risk of cardiovascular events was seen in all cancer survivors (RR: 1.69, 95%CI: 1.31-2.08, P &lt;0.05). The cardiovascular risk was statistically significant in patients with leukemia (RR: 1.71, 95%CI: 1.54-1.88), lung cancer (RR: 1.99, 95%CI: 1.38-2.6) and lymphoma (RR: 1.65, 95%CI: 1.29-2.01), and comparable in breast cancer (RR: 1.22, 95%CI: 0.98-1.46), colorectal cancer (RR: 1.13, 95%CI: 0.89-1.37), prostate cancer (RR: 1.08, 95%CI: 0.99-1.17) and thyroid cancer (RR: 0.96, 95%CI: 0.57-1.35). Conclusion: Our study showed that overall cancer survivors had significant risk for cardiovascular events; mainly leukemia, lung cancer, and lymphoma patients had a significant result. Early identification, continuous monitoring, and proactive management strategies are essential to mitigate the long-term cardiovascular effects of cancer treatments.
Abstract Su805: Early-Latency Evoked Brain Response Revealed using Novel Filtering Technique
Authors: Toren Arginteanu, Mingfeng Cao, Fausto Kang, Nitish Thakor, Romergryko Geocadin
Journal: Circulation (2024)

Background: Cardiac arrest (CA) can cause coma in resuscitated patients. Accuracy of prognosis is limited. Presence of brain signals such as somatosensory evoked potential (SSEP) reveals integrity of the thalamocortical pathway, which is necessary for arousal but insufficient to predict positive outcome. The N10 is a SSEP component that diminishes in CA. The N7, which can be obscured by stimulus artifact or other components, is associated with subcortical structures. Phase space area (PSA) quantifies SSEP morphology and is associated with CA recovery. It has been measured at least 5ms after stimulus. Hypothesis: Early SSEP and PSA diminish under anesthesia and during CA but may recover afterwards. Aims: By removing stimulus artifact, we capture early SSEP (N7 and early PSA) to enable improved prognostication. Methods: Six rats received 1.2, 1.8, and 2.5% isoflurane anesthesia for 30min. Two underwent 5 or 7min CA and were observed over 2hr. SSEP was recorded every 2s. An adaptive filter removed the artifact. Peaks were measured near 7 (N7) and 15 (N10) ms post-stimulus. PSA, the area occupied by the phase space curve, was recorded over 0-9ms (“early”) and 0-30ms (“total”). Signal-to-noise ratio (SNR) is the ratio of N10 amplitude to standard deviation of the signal. T tests were used for comparisons between SNR values and between experimental conditions. Results: We identified 4153 N7 peaks with latency (mean±95% C.I.) 8.6±1.3ms in the filtered data, compared to 2464 with latency 8.5±1.4ms in the unfiltered data. SNR was greater in the filtered signal (2.3±1.5) than unfiltered (0.3±0.4). N7 amplitude decreased at the highest anesthesia level; N10 decreased for each level. N7 and N10 decreased during CA and recovered after, although N10 remained below baseline during 2hr recovery. Early PSA was lower under the higher anesthesia levels, while total PSA decreased for each level. PSA decreased during CA and recovered after 5min CA; total PSA recovered to baseline and early PSA exceeded it after 2hr.Early PSA did not recover from 7min CA, while total PSA recovered but remained below baseline. Conclusion: We demonstrate a novel technique to discover an elusive early-latency response, adding detail to a neural pathway involved in arousal. We reduce noise, capture N7 consistently, and measure PSA beginning at 0ms, providing additional diagnostic dimensions responsive to anesthesia and CA. Future study will investigate outcomes in resuscitated patients.