tbuckley/cabot-search huggingface dataset:
Abstract 4121816: Viral Venture: A Case of Myocarditis and IgA Vasculitis from Adenovirus Infection
Authors: Ryan Khalil, Mohsin Dahodwalla, Joaquim Barboza
Journal: Circulation (2024)

Case Description: A 19-year-old man presented to the emergency department for 3 days of shortness of breath, progressive bilateral lower extremity rash, generalized fatigue, and diffuse joint following an earlier visit to urgent care for pharyngitis symptoms. Physical exam was notable for tachycardia, pain with active wrist and ankle range of motion, pharyngeal erythema, cervical adenopathy, and confluent erythematous palpable purpura and petechiae noted on bilateral lower extremities with scattered lesions on his thighs, arms, and back. Laboratory workup notable for markedly elevated high-sensitivity troponin to 3398 ng/L, and elevated CRP. Further workup was notable for normal urinalysis, negative streptococcus antigen, negative ANCA antibodies, ANA, Hepatitis B and C, and cryoglobulins. Imaging and cardiac workup were notable for normal left ventricular function and cardiac MRI notable for late gadolinium enhancement in the anteroapical mid-myocardial region suggestive of myocarditis. Skin biopsy ultimately revealed immunodeposition of IgA on superficial capillaries compatible with a diagnosis of IgA vasculitis. The patient was started on steroids for IgA vasculitis with rapid improvement in his symptoms and he was discharged home in good condition. Discussion: Recognizing the severe complications of viral infection can lead to prompt treatment and prevention of progression to severe end organ damage. Our case highlights rarely reported cardiac involvement of IgA vasculitis secondary to adenovirus infection based on laboratory and imaging diagnosis with cardiac MRI. To date, only 16 cases of cardiac involvement in IgA vasculitis have been reported. This case adds to the limited body of published cases describing this presentation of IgA vasculitis and is also consistent with the results of prior cases suggesting that an immunosuppressive regimen including glucocorticoids may help to prevent disease progression and induce remission in cases with cardiac involvement without the need for endomyocardial biopsy.
Abstract 4116177: Metabolic and Pharmacokinetic Profiling of Ketone Ester by Background SGLT2 Inhibitor Therapy in Heart Failure with Reduced Ejection: A Phase I Clinical Trial
Authors: Senthil Selvaraj, Caroline He, Elizabeth Thompson, Christoph Hornik, Adam Devore, Chetan Patel, Robert Mentz, Marat Fudim, Lydia Kwee, Lacey Taylor, Stephanie Milosovic, Melissa Hurdle, William Cade, Olga Ilkayeva, Michael Muehlbauer, Christopher Newgard, Daniel Kelly, Payman Zamani, Kenneth Margulies, Svati Shah
Journal: Circulation (2024)

Background: Growing evidence supports a therapeutic role for ketones in HFrEF. However, no pharmacokinetic (PK) studies are available to guide further investigation, and uncertainty exists regarding use with the ketogenic SGLT2i and dose-dependent effects. Methods: We conducted a phase I trial of two doses of ketone ester (KE, 250 mg/kg and 500 mg/kg) in 20 HFrEF participants, stratified by SGLT2i use. Non-compartmental analysis assessed PK parameters of ketones. Paired t-tests and generalized linear mixed models assessed changes in mass-spectrometry based targeted metabolites, blood gas, and vital sign assessments up to 4 hours after dosing. Results: The mean age was 66.0±14.8 years, 45% were women, 30% were non-White, and average EF was 33±13%. The median (25 th –75 th percentile) T max , C max , and T 1/2 for total ketones with 250 and 500 mg/kg doses were 1.01 (0.64-1.24) and 1.58 (1.06-1.99) hours, 2317 (2165-2491) and 3354 (3291-3538) µM, and 0.85 (0.66-1.24) and 2.04 (1.36-3.47) hours, respectively ( Figure 1A ). One hour after KE consumption, insulin levels robustly increased, while non-esterified fatty acids, branched-chain amino acids, and acylcarnitines decreased except for C2/C4-OH acylcarnitines, which increased (FDR-adjusted p-value&lt;0.05). Increases in ketones and C2/C4-OH acylcarnitines were dose-dependent, while background SGLT2i was associated with blunting of the decrease across acylcarnitines. One hour post KE, heart rate initially rose by 4 (95%CI 2-6) beats/min, while systolic blood pressure (-7, 95%CI -12, -2 mmHg), pH (-0.07, 95%CI -0.08, 0.05), and bicarbonate (-3, 95%CI -4, -2 mEq/L) decreased, with dose-dependent acid-based effects ( Figures 1B-C ). These values returned close to baseline by 4 hours. Adverse events were infrequent and mild. Conclusions: Acute KE ingestion is associated with rapid changes in several key metabolic pathways, with differential effects imparted by background SGLT2i (fatty acid metabolism) and dose (ketone metabolism). Hemodynamic effects were transient and irrespective of dose/SGLT2i, while acidotic effects were heightened with increasing dose. These data support the safety of combined KE and SGLT2i in HFrEF and provide grounding data for further trials.
Abstract 4118735: Interpretable deep learning translation of GWAS findings for drug repurposing in Atrial Fibrillation
Authors: Reina Tonegawa-Kuji, JIelin Xu, LIjun Dou, Yuan Hou, John Barnard, Mina Chung, Feixiong Cheng
Journal: Circulation (2024)

Introduction: Translating human genetic findings, such as genome-wide association studies (GWAS) to pathobiology and the discovery of therapeutic target remains a major challenge for Atrial Fibrillation (AF). We previously published a network topology-based deep learning framework to identify disease-associated genes (NETTAG). Hypothesis: By using a deep learning framework, we can efficiently identify AF risk genes, druggable targets, and candidates of repurposable drugs. Aims: To identify potential AF related genes and repurposable drug candidates using our deep learning framework. Methods: First, we collected the reported quantitative trait loci (QTLs) for AF from human heart tissues. Then, we identified the overlaps between the QTLs and the previously reported 150 AF GWAS loci in the latest meta-analysis. We previously built a comprehensive human protein-protein interactome using 18 publicly available databases, containing 351,444 unique PPIs and 17,706 proteins. Using the human protein-protein interactome and the overlaps between AF GWAS hits and QTLs, we prioritized genes and defined the genes with the top 1 % predicted score as AF risk genes (afRGs) using the NETTAG. Then, we assembled drugs from the Drugbank database relating 2,938 FDA-approved drugs or clinically investigated molecules. Using network proximity approaches to evaluate the closest distance between afRGs and a drug’s targets within the human protein-protein interactome, we computationally predicted drugs for AF using Z scores &lt;-2.0. Results: We first collected the overlaps between AF GWAS hits and QTLs, which constituted 27 expression and 12 splicing QTLs. Via NETTAG, we identified 176 afRGs. Among the 176 predicted afRGs, 12 proteins (gene products of afRGs) have been identified as known drug targets with FDA-approved medicines. In total, 1,275 targets have been widely investigated as therapeutic targets for treating AF. Using the closest-based network proximity approach, we computationally identified 49 candidate drugs. These included drugs both reportedly potentially treating AF, such as Pioglitazone (Z=2.29), Telmisartan (Z=-2.52), Sildenafil (Z=-2.86), and those have never been reported before, such as Balsalazide (Z=-2.32). Conclusion: Using a deep learning methodology that utilized GWAS and QTL findings, we identified risk genes and repurposing drug candidates for AF.
Abstract 4115801: Assessing Prevalence of Cardiac Amyloidosis at the Time of Spinal Laminectomy for Spinal Stenosis
Authors: Lidiya Sul, Lauren Ives, Richard Schlenk, Iain Kalfas, Thomas Mroz, Doug Orr, Edward Benzel, Ajit Krishnaney, Dominic Pelle, Claudiu Cotta, Megan Nakashima, Michael Steinmetz, Scott Kilpatrick, John Reith, Mazen Hanna
Journal: Circulation (2024)

Introduction: Cardiac amyloidosis (CA) involves deposition of amyloid fibrils within cardiac myocardium, resulting in heart failure. Recent studies have shown an association between amyloid deposition in the ligamentum flavum (LF) and development of CA. Our study aims to investigate the prevalence of CA in patients identified with amyloid deposition in their LF at the time of spinal laminectomy for spinal stenosis, employing a comprehensive approach integrating multi-modality imaging and laboratory testing. Methods: This is a retrospective study of patients age &gt;50 years old who underwent spinal laminectomy for non-congenital spinal stenosis or spondyloarthropathy. LF tissue samples obtained during surgery were examined histologically for amyloid deposition. Patients with positive findings underwent testing, including serum markers, echocardiography, and 99mtechnetium pyrophosphate (99mTcPYP) scintigraphy. Additionally, cardiac magnetic resonance imaging (cMRI) was obtained when clinically appropriate to assess for CA. Results: Among the 197 enrolled patients, 39 (19.3%) exhibited amyloid deposition in LF tissue. Patient demographics and clinical characteristics did not significantly differ between the positive and negative groups (Table 1). Of the 39 amyloid positive specimens, subtyping using mass spectrometry identified 1 (3%) light-chain, 28 (72%) transthyretin (TTR), and 10 (25%) were unable to be subtyped. Of the 28 TTR positive patients, 8 were of the wild type genotype. Furthermore, 18 of the 28 TTR patients underwent 99mTcPYP scintigraphy, of which none had cardiac uptake consistent with TTR amyloidosis; the other 10 declined work up. Of the 10 untyped patients, 6 had 99mTcPYP scintigraphy with none of the patients having cardiac uptake. Adjunctive cMRI in select positive patients showed findings inconsistent with amyloid deposition. Serum NT-proBNP, Troponin T, and serum pre-albumin levels were similar between groups. Conclusion: Amyloid deposition in LF tissue did not correlate with cardiac manifestations of amyloidosis at the time of surgery. Longitudinal investigation is ongoing to better understand the relationship between amyloid deposition in LF tissue and the development of CA over time.
Abstract 4115652: Effect of the sodium-glucose co-transporter 2 inhibitor, Dapagliflozin, on ventricular repolarization electrocardiographic parameters: DAPA-ECG study
Authors: Rodrigo Campos, DALMO MOREIRA, Gabriel Fonseca
Journal: Circulation (2024)

Background: In patients with type 2 diabetes (T2D), hyperglycemia and glycemic variability lead to prolongation and greater heterogeneity of ventricular repolarization, manifested on the electrocardiogram through an increase in QT, QTc, TpeakTend (TpTe) intervals and the TpTe/QT ratio, increasing the risk of potentially malignant arrhythmias. Dapagliflozin has demonstrated efficacy in reducing cardiovascular events in T2D patients and in the risk of serious ventricular arrhythmias and sudden cardiac death. However, the exact mechanisms by which dapagliflozin confers this protection have not yet been fully elucidated. Goals/Aims: The main objective of the study was to evaluate the impact of dapagliflozin on the TpTe interval of patients with T2D, and secondarily, it examined its impact on various electrocardiographic parameters such as the QT and QTc intervals, the TpTf/QT ratio, QT dispersion, J-T peak interval, QRS-T angle and heart rate. Methods: This randomized, prospective, multicenter and open-label study involved 174 patients with T2D, divided into two groups: one treated with dapagliflozin and the other with optimized medical therapy without iSGLT2. Clinical, electrocardiographic, laboratory and echocardiographic evaluations were carried out at the beginning and after three months. The statistical analysis included means, standard deviations, quartiles, and frequencies, with 95% confidence intervals, using Chi-square (or Fisher) and t-test (or Mann-Whitney) for initial differences, and a linear mixed-effects model to evaluate the results, adopting a significance level of 0.05. Results: The TpTe interval was significantly reduced in the dapagliflozin group from 76.87 ± 12.47 to 67.80 ± 10.34 (p&lt;0.001), and the QTc interval reduced from 424.07 ± 30.76 to 411.26 ± 25.31 (p=0.022). The TpTe/QT ratio in the dapagliflozin group was shortened from 0.20 ± 0.03 to 0.18 ± 0.02 (p&lt;0.001). Both groups showed reductions in mean blood glucose and HbA1c, with a greater decrease observed in the control group. No significant changes were recorded in other variables analyzed. Conclusion: In patients with T2D, dapagliflozin significantly reduced the duration of the TpTe and QTc intervals, in addition to the TpTe/QT ratio. These findings indicate a decrease in ventricular electrical remodeling with a potential cardioprotective effect of dapagliflozin, which would partly explain its benefits in reducing potentially malignant ventricular arrhythmias and sudden cardiac death.
Abstract 4120680: Language AI Chat BOTs as Pioneers in Cardiovascular Diagnosis? A Retrospective Analysis on Real-Time Patients in a Tertiary Care Centre
Authors: Azka Naeem, Syed Mujtaba Baqir, Omair Khan, Kundan Jana, Fizza Mohsin, fatima sajid, oo Aung, Avleen kaur, Victor Wong, VIJAY SHETTY, Kseniya Slobodyanyuk
Journal: Circulation (2024)

GPT-3 and GPT-4, show promise in assisting healthcare professionals with clinical questions. Their performance in real-time clinical scenarios, particularly with cardiovascular symptoms, remains underexplored. This study aims to evaluate their precision and reliability compared to physicians. Hypothesis: We hypothesize that board-certified emergency department attendings at Maimonides Medical Center exhibit higher accuracy and reliability than GPT-3.5 and GPT-4 in generating differential diagnoses based on history and physical examination for patients presenting to the emergency department. Methods: Patient data from Maimonides Medical Center's emergency department, collected from January 1, 2023, to April 30, 2023, was analyzed. Demographics, symptoms, medical history, and discharge diagnoses recorded by emergency room attendings were examined. ChatGPT-3.5 and GPT-4 generated differential diagnoses, which were compared with those by attending physicians. Accuracy was determined by comparing each rater's diagnoses with discharge diagnosis, calculating the proportion of correctly identified cases. Precision was assessed using Cohen's kappa coefficient and Intraclass Correlation Coefficient to measure agreement between raters. Results: Patient demographics showed mean age of 49.12 years, with 57.3% males and 42.7% females. Chief complaints included fever/sepsis (24.7%), gastrointestinal issues (17.7%), and cardiovascular problems (16.4%). Diagnostic accuracy against discharge diagnoses was highest for Chat GPT-4 (85.5%), followed by Chat GPT-3.5 (84.6%) and ED attendings (83%). Cohen’s kappa demonstrated moderate agreement (0.7) between AI models, with lower agreement observed for ED attendings. Stratified analysis revealed higher accuracy for gastrointestinal complaints with Chat GPT-4 (87.5%) and cardiovascular complaints with Chat GPT-3.5 (81.34%). Conclusion: Our study demonstrates that Chat GPT-4 and GPT-3.5 exhibit comparable diagnostic accuracy to attendings, highlighting their potential to aid decision-making in dynamic clinical settings. The stratified analysis revealed comparable reliability and precision of the AI chat bots for cardiovascular complaints which represents a significant proportion of the high risk patients presenting to the emergency department. This study contributes to integrating AI models into medical practice, enhancing efficiency and effectiveness in clinical decision-making
Abstract 4121039: Refining the American Heart Association Predicting Risk of Cardiovascular Disease EVENTs (PREVENT) equations using depression and anxiety disorder
Authors: Shinya Nakada
Journal: Circulation (2024)

Background: Growing evidence has suggested associations of common mental health conditions including depression and anxiety disorder with CVD, but no studies have examined their incremental predictive values in PREVENT (AHA Predicting Risk of CVD EVENTs). Research questions: Does including anxiety and/or depression improve the PREVENT predictive performance? Aims: We used a range of measures of anxiety and depression and combinations to examine whether these conditions improved the prediction performance of PREVENT. Methods: New risk prediction models were developed and internally validated using 60% and 40% of the UK Biobank cohort data, respectively. Mental health predictors included: depressive symptom score based on the four-item Patient Health Questionnaire and self-reported and record-based anxiety and depression diagnoses before baseline. CVD events were ascertained through hospital admission and death certificate data after baseline. The Cox proportional hazards models were used to calculate coefficients and 95% confidence intervals. The incremental predictive values were examined by adding the mental health predictors to the PREVENT predictors based on Harrell’s C-indices, sensitivity, specificity, positive and negative predictive values, and net reclassification improvement indices (NRIs). Results: Of the 502,366 UK Biobank participants, 195,489 were included in the derivation set and 130,326 were included in the validation set. In the validation set, the inclusion of each mental health measure produced an increase in C-index and higher sensitivity, specificity, and positive and negative predictive values compared with the PREVENT equations, with the greatest improvements for depressive symptom score. Depressive symptom score produced the greatest improvements in net reclassification overall (NRI 0.84, 95% CI 0.46–1.20) and this was further improved by adding recorded anxiety and depression (NRI 0.89, 95% CI 0.52–1.24). In addition, depressive symptom score showed better discrimination and NRI in both female and male validation sets. Conclusions: Our findings suggest that including depressive symptom score in PREVENT could improve the prediction of CVD with low cost and without invasive procedures.
Abstract 4115684: Outcomes Associated with Remote Monitoring without In-person Evaluations for Patients with Cardiovascular Implantable Electronic Devices
Authors: Laura Derry, Mary Whooley, Merritt Raitt, Thomas Rotering, Hui Shen, Gary Tarasovsky, Sanket Dhruva
Journal: Circulation (2024)

Introduction: Traditionally, patients with cardiovascular implantable electronic devices (CIEDs: pacemakers and implantable cardioverter-defibrillators) attend in-person visits at least annually, paired with remote monitoring (RM). Because similar data are obtained through RM and in-person visits, it is unclear whether routine in-person visits are necessary. Two small trials conducted outside the U.S. found no difference in clinical outcomes without routine in-person visits for patients engaged in RM, but their generalizability is uncertain. Research Aim: To determine whether routine visits for CIED care are associated with major adverse cardiac events (MACE) among patients in the U.S.’ largest public integrated health system, the Veterans Health Administration (VHA). Methods: We classified Veterans who received their CIED care within VHA and sent ≥1 RM transmission between 7/1/20-6/30/21 into one of three groups based on type of clinical encounters for CIED care: (1) any in-person, (2) virtual-only (telephone and/or videoconference), or (3) no in-person or virtual visits. Data were obtained from the VHA National Cardiac Device Surveillance Program and Corporate Data Warehouse. The primary outcome was MACE, a composite of all-cause mortality, stroke, and cardiac hospitalization, between 7/1/21-6/30/22. We performed multivariable logistic regression, adjusting for patient and device characteristics. Results: Of 40,366 patients, 27,298 (68%) had at least one in-person visit, 9,268 (23%) had only virtual visits, and 3,800 (9%) had neither. Mean age was 73 years, 97% were male, and 37% lived in rural areas. There were 6522 (23.9%) MACE events among patients who had in-person visits, 2116 (22.8%) among those who had only virtual visits, and 947 (24.9%) among those who had no visits. After multivariable adjustment, there was no significant association between encounter type and MACE [odds ratio 0.93 (95% CI: 0.85-1.01) for patients who had any in-person or virtual visits compared to those without]. Conclusion: Among patients engaged in RM, the odds of MACE was similar regardless of whether patients had in-person or virtual visits versus no visits. Although there could be unmeasured confounding, these results suggest routine in-person or virtual visits may no longer be necessary for CIED care with RM. Patients, clinicians, and healthcare systems could benefit by reducing low-value visits and re-focusing resources on visits that yield actionable interventions.
Abstract 4119891: Risk Factors of Anemia in Pulmonary Arterial Hypertension Patients with Endothelin Receptor Antagonists Administration and Related Treatment
Authors: Li Xin, Zhihui Zhao, Qin Luo, qing zhao, Qi Jin, Yi Zhang, Zhihua Huang, Anqi Duan, sicheng zhang, Luyang Gao, Yijia Wang, Sicong Li, Zhihong Liu
Journal: Circulation (2024)

Background: Endothelin receptor antagonists (ERAs) demonstrated significant efficiency in delaying clinical deterioration and improving survival of patients with pulmonary arterial hypertension (PAH). However, the frequent occurrence of anemia after ERAs administration has gained clinical attention currently, whereas the etiology of anemia is unclear. The risk factors of ERAs associated anemia remained undefined. Therefore, we aim to investigate risk factors of developing anemia after ERAs treatment and whether iron supplement could correct anemia. Method: A retrospective cohort study was performed among patients with PAH who received ERAs between January, 2017 and December, 2019 in Fuwai hospital. The primary outcome was development of anemia after ERAs therapy and secondary outcome was correction of anemia after iron supplement. Results: A total of 120 patients with PAH were included in the study and 28 patients developed anemia during follow up . Distinctively, all the patients who developed anemia were female. After ERAs administration, iron metabolism (Ferritin 95.29±144.79 μg/L versus 69.9±118.25 μg/L, P &lt;0.001) and hemoglobin (154.21±23.80 g/L versus 136.12±28.61 g/L, P &lt;0.001) reduced significantly in the total cohort with patients who developed anemia more significant. Baseline iron metabolism (Ferritin: HR 0.98, 95%CI 0.96-0.99, P =0.02) was independently associated with development of anemia after ERAs administration. Compared with patients with iron replete, patients with iron deficiency had over 9-fold risk of developing anemia after receiving ERAs (HR = 9.59, 95%CI 3.62-25.41, P &lt; 0.01). Iron supplement could effectively correct anemia. Conclusion: It is advised that patients receiving ERAs monitor iron metabolism and hemoglobin regularly, especially females and those with low hemoglobin level and compromised iron homeostasis before ERAs administration, which facilitates prevention and early detection of anemia. ERAs-related anemia is mostly mild, oral iron supplement could effectively reverse anemia and aberrant iron metabolism.