tbuckley/cabot-search huggingface dataset:
Abstract 202: Liposome-Encapsulated Hemoglobin (HbV) Rescues Hemorrhagic Shock Heart Through Anti-Ischemic and Anti-Arrhythmogenic Effects on Myocardium in Repetitive 65% Bleeding Rat Model
Authors: Bonpei Takase, Yuko Higashimura, Nobuyuki Masaki, Manabu Kinoshita, Hiromi Sakai
Journal: Circulation (2023)

Phase I clinical trial of Liposome-encapsulated hemoglobin vesicles (HbVs) was successfully accomplished. Since several ameliorating mechanisms are not fully understood on HbVs, to investigate its mechanisms of salutary effect on myocardium, optical mapping analysis (OMP) and electrophysiological study (EPS), immunostaining pathological examination for HIF1-alpha in heart and measurement of blood troponin I (TnI) were performed in 30% spontaneous arterial bleedings five times up to approximately total 65% hemorrhage in rats. Eighteen rats in each group were resuscitated by immediately after bleeding by same volume as bleedings each five times by transvenous infusion of 5%albumin solution (ALB-group), washed erythrocytes (wRBC-group) and HbVs (HbV-group). Survival effects over 24 hours were examined. After excising heart, OMP and EPS were performed. All rats died in ALB-group, whereas all survived in wRBC-group and HbV-group. OMP showed impaired (prolonged) action potential duration dispersion (APDd: which is arrhythmogenic index) in LV in ALB-group, whereas APDds were attenuated in HbV-group and wRBC-group (26±4 vs. 11±6, 14±5ms, P&lt;0.05). Lethal arrhythmias (ventricular tachycardia [VT]/ventricular fibrillation [VF]; VT/VF) were provoked by EPS and/or spontaneously occurred in ALB-group whereas not in both wRBC-group and HbV-group. HIF1-alpha was positively stained and TnI levels were significantly elevated only in ALB-group (Peak TnI; 186±47 vs. 64±25, 91±24, 44±10pg/mL, P&lt;0.05: Figure). Conclusions: HbVs rescue lethal hemorrhage through improving lethal arrhythmias and myocardial damages by reflected by inducing HIF1-alpha and elevated TnI. HbVs could be useful for resuscitation and saving life from gun-shot arterial bleeding on-site occurred in terrorisms.
Abstract 18434: Amanita Muscaria and Pantherina Withdrawal as a Cause of Lone Atrial Fibrillation
Authors: Alejandro Cruz Ponce, Hira Akhlaq, Justin Ilagan, Kameron Tavakolian, Anton Mararenko, Ndausung Udongwo, Abbas Alshami, Anas Alrefaee, Joseph Heaton, Chase Contino
Journal: Circulation (2023)

Introduction: The Amanita mushroom family is known for use as a means of suicide or for psychedelic effects. The manifestations of Amanita mushroom poisoning include gastrointestinal poison, cholinergic effects and organ failure. In this paper, we will discuss the first observed study of a patient who developed new onset atrial fibrillation (AF) with rapid ventricular response (RVR) after withdrawal from accidental chronic poisoning of Amanita muscaria and pantherina over the course of three weeks. Case: A 29 year-old male with no prior past medical history presented with three days of palpitations. He began taking A. pantherina and muscaria three weeks prior to help treat sexual addiction. He started with 0.35 mcg twice a day, then doubled the dose after one week, then three days prior to presentation he started taking three grams twice per day. He noticed palpitations as he increased his dose, but then acutely worsened after he stopped taking mushrooms. In the emergency department, he was found to have new onset atrial fibrillation with rapid ventricular rate as well as frequent episodes of nonsustained ventricular tachycardia. An alcohol level and urine drug screen were unremarkable. Thyroid stimulating hormone was within range. His heart rate did not respond to intravenous diltiazem. He was transitioned to an esmolol infusion that responded with rapid improvement in heart rate as well as ventricular ectopy suppression. He eventually underwent a transesophageal echocardiogram and was transitioned to oral beta blocker therapy. He was discharged with no complications and near full recovery. Discussion: A report published in 1869 described the first description of the pharmacological effect of A. muscaria showing it is 143 times more toxic than acetylcholine due to the inability of cholinesterase to hydrolyse or inhibit its effect. The acute cardiovascular toxicities are well described, however, this case is the first description of chronic cardiac toxicity manifesting as new onset AF with RVR, caused by A. muscaria and pantherina withdrawal. We suggest that cardiovascular monitoring, including event monitors, are essential for complications of A. muscaria and pantherina . More detailed studies need to be done.
Abstract 13332: Assessment of Myocardial Oxygenation Response to Vasoactive Breathing Maneuvers in Patients With Repaired Dextro-Transposition of the Great Arteries an OS-CMR Study
Authors: Carlos E Guerrero, Mayssa Moukarzel, Masaki Kodaira, Judith Therrien, Elizabeth Hillier, Ariane J Marelli, Matthias Friedrich
Journal: Circulation (2023)

Introduction: Long-term outcomes of patients with repaired Dextro-transposition of the great arteries (D-TGA) by arterial switch operation (ASO) are excellent. However, studies have suggested impaired myocardial blood flow reserve. Oxygen-sensitive cardiac magnetic resonance (OS-CMR) with vasoactive breathing maneuvers (BM) offers a contrast-free tool for evaluating myocardial oxygenation. Hypothesis: Evaluate myocardial oxygenation reserve and microvascular function in repaired D-TGA post-ASO using OS-CMR with BM. Methods: In this single-center study, we analyzed OS-CMR images (basal and mid-left ventricular slices) of 9 D-TGA post-ASO patients (mean age 29 ±6.52yrs, 33.3% females) and 10 healthy participants (mean age 33 ±8.9 yrs, 40% females) who completed the BM. The BM consisted of free breathing, then hyperventilation, causing vasoconstriction, then breath hold, causing vasodilatation. End-systolic OS-CMR signal intensity (SI) was measured at baseline, after hyperventilation (closest to 0 sec of breath hold), and at closest to 30 sec of breath hold. Changes in SI (ΔSI) in % were calculated in response to the different periods and compared using independent samples t-test. Results: In the D-TGA cohort, the coronary response to hyperventilation was abnormal compared to healthy subjects (5.8±19.9% vs -15.1±13.3%, p=0.01). No difference was observed in ΔSI% during breath hold (mean TGA:3.0±10.5% vs mean healthy:5.7±6%, p=0.5). No differences were observed in mid-slices for either period. Conclusions: Our findings suggest patients with D-TGA may have an impaired vasoconstrictor response to a hyperventilation maneuver. Further studies should explore the associated pathophysiology and potential impact on clinical management.
Abstract 14526: <i>CREG1</i> Deletion Inhibits Autophagy and Causes Cardiomyocyte Damage Under Nutritional Stress
Authors: Russell J Pepe, Yanmei Qi, Leonard Y Lee, Shaohua Li
Journal: Circulation (2023)

Introduction: The cellular repressor of E1A-stimulated genes 1 (CREG1) is a small, highly conserved glycoprotein ubiquitously expressed in mammalian tissues. It localizes in the endosomal-lysosomal compartment and promotes lysosome biogenesis and acidification. The goal of the current study was to elucidate the physiological function of CREG1 in the mouse heart. Hypothesis: We hypothesized that deletion of Creg1 would result in pathological cardiac remodeling following nutritional stress. Methods: We generated whole-body and cardiomyocyte-specific Creg1 KO mouse lines via mating Creg1 fl/fl mice with UBC-Cre-ERT2 and Myh6-Cre mice, respectively. Mice were fasted for 16-40 hours, and hearts were evaluated by H&amp;E staining, immunofluorescence, electron microscopy, and biochemical analysis. Knockout mice were compared to within-litter controls. Results: Under ad lib feeding, some whole-body knockout mice exhibited myofibril disarray and irregular nuclei in the heart. After prolonged fasting, both whole-body and cardiomyocyte-specific deletion of Creg1 resulted in significantly increased intracellular vacuoles, pale cytoplasm, and loss of nuclei in the papillary muscles and interventricular septa ( Figure 1 ). Immunofluorescence staining demonstrated significantly increased size and number of LC3 puncta (an autophagosome marker), and Western blot demonstrated accumulation of LC3II in the Creg1 KO hearts. In Creg1 KO cardiomyocytes, electron microscopy revealed condensed and irregular mitochondria, which lost their registry with myofibers. In addition, mitophagy was impaired and sarcomeric Z-discs were either damaged or obliterated. Conclusion: CREG1 protects the heart from nutritional stress-induced injury, likely through the promotion of autophagic flux.
Abstract 14672: Exercise Hemodynamic Profiles of Resting and Exercise-Based Definitions of Cancer Therapy-Related Cardiac Dysfunction in Anthracycline-Treated Breast Cancer Survivors
Authors: Stephen Foulkes, Erin Howden, Mark J Haykowsky, Yoland Antill, Kristel Janssens, Sophie Nightingale, Leah Wright, Ben Costello, Andre La Gerche
Journal: Circulation (2023)

Introduction: Detection of cancer therapy-related cardiac dysfunction (CTRCD) is a cornerstone of heart failure (HF) risk assessment. However, it is unclear how closely CTRCD definitions reflect typical HF features of reduced exercise tolerance (VO 2 peak) and blunted cardiac reserve. Hypothesis: Standard CTRCD metrics (resting LVEF and GLS) will show poor agreement with reduced VO 2 peak and changes in cardiac reserve following anthracycline chemotherapy (AC). Methods: This analysis used baseline (pre-AC) and 12-month assessments from a randomized trial of exercise training in breast cancer patients (n=104) undergoing AC ± anti-HER2 therapy. Assessments included resting echocardiography (LVEF and GLS), cardiopulmonary exercise testing (VO 2 peak) and exercise cardiac magnetic resonance (peak cardiac output [CO], stroke volume [SV] and LVEF [LVEF peak ]). CTRCD was defined as ≥10% absolute decline in LVEF to a value &lt;50%, &gt;15% decline in GLS, and a ≥10% decline in VO 2 peak from pre-AC. Results: Seventy-nine participants (76%) completed pre-AC and 12-month assessments, 14 of whom (18%) met LVEF and 30 (38%) met GLS CTRCD criteria (10% met both criteria). In addition to declines in resting LVEF and GLS, these participants showed a reduction in LVEF peak , but no change in peak SV, CO or VO 2 peak (Figure 1A-B). In contrast, 19 participants (24%) had a ≥10% VO 2 peak decline (-17% vs Pre-AC, P&lt;0.001) that coincided with a decline in peak SV (-6%, P=0.03), and LVEF peak (-11%, P=0.02), with no significant change in resting LVEF or GLS (Figure 1C). Of those who met VO 2 peak criteria, only three (16%) and five (26%) met LVEF or GLS criteria, respectively, and only one met all three criteria. Conclusions: Whilst capturing reduced global LV systolic function, CTRCD definitions are insensitive to meaningful declines in VO 2 peak and cardiac reserve. Incorporating measures of VO 2 peak into CTRCD surveillance may improve HF risk stratification in breast cancer survivors.
Abstract 15167: The Use of Echocardiography in Patients With Advanced Peripheral Arterial Disease
Authors: Yasser Jamil, Joshua Huttler, Dana Alameddine, Haoran Zhuo, Carlos Mena-Hurtado, Eric J Velazquez, Raul J Guzman, Cassius I Ochoa
Journal: Circulation (2023)

Introduction: Patients with peripheral arterial disease (PAD) are at high risk of concomitant cardiac diseases. Transthoracic echocardiography (TTE) is a common imaging modality to assess cardiac function and is used as a screening tool, especially for patients with advanced PAD undergoing lower extremity revascularization (LER). The current study evaluates the incidental use of TTE in patients undergoing LER. Hypothesis: Patients with a perioperative TTE have improved outcomes compared to patients who do not undergo TTE. Methods: The electronic records of patients undergoing LER between 2013-2020 were reviewed. All TTE within 6 months of initial LER were captured. Patient characteristics and outcomes were compared between patients who underwent TTE and those who did not. Results: A total of 1,988 patients underwent LER, and 69.3% (N=1,377) had TTE. Patients in the TTE group were more likely to be African American and have diabetes mellitus, chronic kidney disease, and coronary artery disease. Patients with TTE were more likely to be on aspirin and undergo open/hybrid revascularization. There was no significant difference between the 2 groups in perioperative MI, major amputation, or mortality. Furthermore, patients with TTE had higher MALEs. (Table) However, there were no differences in MALE-free survival between the two groups (Figure 1) Conclusion: TTE was obtained in 69.3% of patients with advanced PAD undergoing LER but did not seem to be associated with outcomes in this institutional series. Further research is warranted to identify PAD patients that would benefit from TTE prior to LER.
Abstract 16391: Pro-Neoplastic Properties of Small Extracellular Vesicles From Failing Hearts
Authors: Tal Caller, Itai Rotem, Olga Shaihov–Teper, Daria Lendengolts, Yeshai Schary, Ruty Shai, Efrat Glick-Saar, Dan Dominissini, Alex Boomgarden, Crislyn D'Souza-Schorey, Nili Naftali Shani, Jonathan Leor
Journal: Circulation (2023)

Background: Heart diseases are associated with an increased incidence of cancer independently of shared risk factors. The mechanism beyond this link is complex, unclear and limits our ability to develop effective therapies. We aimed to test the hypothesis that small cardiac extracellular vesicles (sEVs) contribute to the link between HF and cancer. Methods &amp; Results: We used mouse models of heterotopic and orthotopic lung cancer and post-myocardial infarction (MI) heart failure (HF). sEVs were isolated by size exclusion chromatography. To determine the role of cardiac EVs in tumor growth, we focused on sEVs from cardiac mesenchymal stromal cells (cMSCs). cMSCs after MI secreted twice more sEVs, characterized with a unique proteome, compared with cMSCs from sham-MI ( Fig 1A ). cMSC-sEVs from post-MI HF harbored more tumor-promoting cytokines and microRNA (miR), such as periostin, osteopontin, IL-6, TNFα, galectin-3, and miR's 221 and 21. The pro-neoplastic effects of cMSC-sEVs on cancer cells were depended on cancer type, with a marked increase in proliferation and migration of lung and colon cancer cells but only a modest increase with more malignant triple-negative breast and melanoma cancer cells. Next, we inoculated lung cancer cells into mice and found that post-MI HF accelerated tumor growth. Furthermore, adoptive transfer of cMSC-sEVs from failing hearts accelerated tumor growth with and without systemic EV depletion ( Fig 1B ). Finally, we found that spironolactone mitigated the neoplastic effects of HF, attenuated tumor growth ( Fig 1C ), and reduced the number of cMSC-sEVs by 26%. Conclusions: We show, for the first time, that cardiac extracellular vesicles from post-MI failing heart harbor pro-neoplastic properties and promote tumor growth independently of other secreted factors. Spironolactone reduces the number of cardiac extracellular vesicles and the pro-neoplastic effects of post-MI heart failure.
Abstract 17815: Effectiveness of Artificial Intelligence in Triaging Transmissions From Cardiac Implantable Electronic Devices
Authors: Danish Bawa, Adnan Ahmed, Rajesh Kabra, shanti l bansal, Eric Olsen, Ilyas Colombowala, Rachad Ghazal, Naga Venkata Pothineni, Douglas J Darden, Rakesh Gopinathannair, Dhanunjaya R Lakkireddy
Journal: Circulation (2023)

Background: Monitoring of cardiac implantable electronic devices (CIED) may cause tremendous burden on device clinics. Multiple transmissions for device alerts pose challenges in terms of triaging and clinical action. In this study we compared the effectiveness of artificial Intelligence (AI) as compared to Device technicians (DTs) in triaging the data from CIED. Methods: The study included remote transmissions from CIEDs being monitored at 78 clinics across USA from Jan to April 2023. Transmissions were initially processed by AI and were either dismissed, forwarded to the DT for review or forwarded directly to the device clinic. The data forwarded to the DT was analyzed and was either dismissed or forwarded to the device clinic with and without alerts. Transmissions were further classified based on urgency of response needed. About 15% of all transmissions processed by AI and DT were randomly examined by EP for accuracy. Results: A total of 42,534 patients with CIEDs generated 273,435 transmissions. Of these, 21% (57,345) transmissions were dismissed by AI - 17.8% (38,530) without alerts and 33.1% (18,815) with alerts. Of the transmissions dismissed, alerts for AT/AF represented the largest proportion in DT group, whereas alerts for pacing percentage was most seen with AI (table 1). Similar trends were seen with transmissions that were forwarded to clinics with pacing percentage dominating in AI group, and AT/AF detection in the DT group (table 2). Conclusion: In our study, compared to DT, AI algorithm was found to be more accurate in overall triage of remote transmission data and has the potential to improve the clinical efficiency of device clinics and care of patients with CIEDs.
Abstract 16194: Relationship Between Change in Global Longitudinal Strain and Sustained Handgrip Induced Afterload as Assessed Using Invasive Left Ventricular Pressure Measurements and Machine Learning Analytics
Authors: Meiling Chen, Mi-Ok Kim, Krishan Soni, Victoria Liu, Richard Cheng, Yerem Yeghiazarians, Harsh Agrawal, Aaron Grober, Adriana Martin, Hernan Vera Sarmiento, Thomas Ports, Theodore Abraham
Journal: Circulation (2023)

Introduction: Global longitudinal strain (GLS) is a sensitive, quantitative measure of left ventricular (LV) systolic function and affected by afterload. We sought to compute the impact of LV systolic pressure (LVP) increase on GLS using handgrip stress during invasive LVP measurements. Methods: Patients undergoing left heart catheterization (n=51; mean age 64+/-11 years; 31% women; Table) for standard of care indications underwent echocardiography during handgrip stress with a catheter in the LV cavity. GLS and LVP were measured simultaneously over 15 seconds of continuous handgrip. GLS and LVP relationships were analyzed using linear regression and machine learning methods. Results: Sustained handgrip (HG) stress significantly increased LVP and reduced GLS. There was no significant correlation between resting and peak HG stress LVP and GLS (p= 0.32 &amp; 0.36, respectively). However, change in GLS was significantly correlated with change in LVP (p&lt;0.0001; Figure) with every 10 unit increase in LVP associated with a 0.6 reduction in GLS. The penalized maximum likelihood machine learning method was used to select key factors associated with the within subject slope of % change in GLS over % change in LVP (median slope -0.53; IQR-0.91 to -0.29). LV ejection fraction was identified as an important predictor of the GLS-LVP slope. LV ejection fraction was significantly associated with the slope (p=0.0005; Figure) with a 10 unit increase in LV ejection fraction corresponding to 0.22 increase in the slope. Conclusions: LV afterload is associated with significant decrements in GLS. LV ejection fraction is an important predictor of the GLS-LVP slope. These data provide the foundation to build models that would account for change in LVP during serial measurements of GLS thus allowing reliable comparison of repeated GLS measurements.
Abstract 13788: Association Between Floroquinolones and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis
Authors: NEHA VERMA, Vikash Jaiswal, Amira Mohamed Taha, Novonil Deb, Endurance O Evbayekha, Shiva Gupta, ROMARIE JOY CASTILLO, Abhigan Babu Shrestha, Vagisha Sharma, Akanksha Sharma, Alaa Ramadan, Kripa Rajak, David Song, Abdelrahman Attia, Prachi Sharma
Journal: Circulation (2023)

Background: The administration of Fluoroquinolones (FQ) has raised concerns regarding potential adverse cardiovascular outcomes, including severe arrhythmias, myocardial infarction, and even mortality. Nevertheless, a comprehensive evaluation of these outcomes and their real impact on patients receiving these antibiotics is lacking. Objective: We aim to evaluate the association between fluoroquinolones and cardiovascular outcomes.Methods: We systematically searched all electronic databases from inception until 27th May 2023. Odds ratios (OR) with corresponding 95% confidence intervals (CI) were calculated, with a p-value &lt;0.05 considered statistically significant. Results: The final analysis included a total of 11 studies, encompassing a sample size of 6,579,936 individuals (FQ: 2,005,466 and control: 4,574,470). The pooled analysis shows that the FQ group was associated with significantly higher risk arrhythmia (OR: 1.87 (95% CI: 1.22, 2.87), P&lt;0.01, cardiovascular mortality (OR: 1.72 (95% CI: 1.38, 2.14), P&lt;0.0001), and myocardial infarction (OR: 1.33 (95% CI: 1.26, 1.39), P&lt;0.0001). Conclusion: Fluoroquinolones exhibit a significant cardiotoxic effect, contributing to the development of arrhythmias, myocardial infarction, and even mortality. Consequently, caution must be exercised when prescribing this class of antibiotics, with regular follow-up recommended to monitor potential cardiovascular complications.
Abstract 13656: Effects of Left Ventricular Ejection Fraction and NYHA CHF Class on Baroreceptor Function in Congestive Heart Failure
Authors: Christina Beegle, Daniel Gulko, Jacqueline Kenitz, Gregory Petrossian, Mikhail Torosoff
Journal: Circulation (2023)

Background: Autonomic dysfunction is an important component in congestive heart failure (CHF) pathophysiology. The combined effects of reduced ejection fraction and advanced CHF Class on baroreceptor function in CHF have not been well investigated. Methods: A single center prospective study included 118 consenting patients, 68.3 ± 14.2 years old, 50 females (42.3%), BMI of 30.1 ± 8.5 kg/m 2 , with histories of HTN in 97 (82.2%), CAD in 64 (54.2%), diabetes in 49 (41.5%), and COPD or asthma in 39 (33.1%). Class I or II CHF were documented in 32 (27.1%), class III in 53 (44.9%), and class IV in 33 (28%) patients. Mean LV EF was 44.5+/-13.9%, HFrEF was present in 41 (34.7%) patients. Baroreceptor function was assessed by measuring resting and lowest heart rates (HR) during voluntary breath holding. Results: Despite treatment with beta-adrenergic blockers in 92 (78%) and non-dihydropyridine calcium channel blockers in 7 (5.9%) patients, increased CHF class was associated with significantly increased resting (71.7 ± 14.4 bpm in Class I-II, 73.1 ± 13.6 bpm in Class III, and 80.8 ± 16.9 bpm in Class IV, p=0.027) and breath holding HR (68.9 ± 15.3 bpm in Class I-II, 69.9 ± 12.2 bpm in Class III, and 80 ± 16.1 bpm in Class IV, p=0.002). In addition, when compared to the rest of the cohort, HFrEF patients manifested with increased resting (80.9 ± 14.5 vs. 71.6 ± 14.6 bpm, p=0.001) and breath holding HR (77.6 ± 13.9 vs. 69.7 ± 14.7 bpm, p=0.006). In multivariate analysis, both increased CHF NYHA class and reduced LVEF retained statistically significant independent effects on resting (p=0.037 and p=0.001, respectively) and breath holding HR (p=0.005, each). Conclusion: Decreased LV ejection fraction and increased CHF class independently and significantly contribute to autonomic dysfunction in CHF patients. Heart rate changes indicating abnormal baroreceptor function in CHF patients are apparent despite treatment with medications affecting chronotropic response.