tbuckley/cabot-search huggingface dataset:
Abstract 17883: Subacute Native Aortic and Mitral Valve Endocarditis Manifesting as Embolic ST-Elevation Myocardial Infarction
Authors: karthik sreedhara, Jason Nasser, Megan McGervey
Journal: Circulation (2023)

Case description: A 54-year-old male presented with one day of substernal chest pain. He also reported two months of malaise, myalgias, chills, and intermittent fevers. Medical history was notable for well-controlled hypertension and negative for dyslipidemia, diabetes, or drug and tobacco use. Family history was negative for premature coronary artery disease. Vitals were notable for fever of 103F, blood pressure of 108/56 mmHg, and heart rate of 88 beats per minute. Physical exam showed bounding pulses and a soft diastolic murmur at the left lower sternal border. Electrocardiogram showed inferior lead ST-elevations. He was taken for cardiac catheterization and found to have a totally occlusive thrombus in the distal right coronary artery with minimal disease in the remaining vessels. He underwent aspiration thrombectomy and placement of drug eluting stent with normal flow. He was transferred to the coronary intensive care unit. Labs showed mild leukocytosis, normal serum creatinine, and unremarkable urinalysis. Echocardiogram showed a 1.7 x 0.5 cm mobile echodensity on the aortic valve with severe aortic regurgitation and a small echodensity on the anterior mitral leaflet. Blood cultures grew Enterococcus faecalis. A CT scan of the head, chest, abdomen, and pelvis revealed no embolic disease. He underwent urgent surgery due to concern for infective endocarditis with coronary embolism. Purulence was found at the stent site and the posterior descending artery was obliterated by necrotic tissue. A bypass graft was placed distal to the stent site and infected territory was unroofed and irrigated. Mitral and aortic valve replacement was performed. He tolerated surgery and was discharged with 6 weeks of intravenous antibiotics. Discussion: This case was unique in the subacute chronicity of endocarditis and lack of other systemic emboli. Clinically relevant coronary embolism was reported in only 1.5% of cases of infective endocarditis but microemboli were found in 60% postmortem. Embolization is more common with mitral valve involvement, &gt;10 mm vegetation, and fungal or staphylococcal disease. Angiographic evidence of heavy thrombus burden or lack of significant atherosclerosis after myocardial infarction may prompt evaluation for coronary embolism.
Abstract 16419: Assessing the Evidence Base of Cardiology-Specific Oncology Guideline Recommendations: Implications for Health Policy
Authors: Nikita Jhawar, Artur Schneider, Fred Kusumoto
Journal: Circulation (2023)

Introduction: Oncology societies have been contributing guidelines/recommendations to the limited yet growing body of literature in cardio-oncology. Research Questions: What are the levels of evidence (LOE) and classes of recommendation (COR) for cardiology-specific recommendations produced by major oncology societies? Methods: We reviewed cardiology-specific recommendations published by the American Society of Clinical Oncology (ASCO), American Society of Hematology (ASoH), NCCN (National Comprehensive Cancer Network), and European Society of Cardiology (ESC). LOE and COR were noted for each recommendation. Results: The US oncologic societies have made 81 cardiac-specific recommendations (ASCO: 54 (67%); ASoH: 14 (17%); NCCN; 13 (16%) (Tables 1-3). For ASCO, 26 (48%) were COR 1, 23 (43%) COR 2, and 5 (9%) COR 3 supported by LOE A (9%), LOE B (39%), and LOE C (52%). For ASoH, 1(8%) was COR 1, 11(85%) COR 2, and 1(8%) COR 3 supported by LOE B (7%), and LOE C (93%). NCCN made 13 COR 2 recommendations and did not provide LOE classification. The most common recommendations addressed baseline (20%) and serial (24%) assessment, specific imaging modalities (9%), chemotherapy dosing (19%), and radiation therapy (20%). Most recommendations were unique without discrepant statements, but there were some redundancies. ESC produced 271 cardio-oncology recommendations (155 COR 1; 111 COR 2; 5 COR-3) with 3% LOE A, 21% LOE B, and 76% LOE C. The major areas for ESC recommendations included baseline (18%) and serial (33%) assessment, and medications (29%). Conclusions: Oncology and cardiology professional society guidelines have provided 352 cardiac related recommendations in the setting of cancer treatment and 73% have the lowest LOE. In this developing field with a limited evidence base, close collaboration between cardiologists and oncologists will be required to provide a cohesive set of recommendations for the cardiac issues associated with cancer treatment.
Abstract 17777: Sorafenib Aggravates Atherosclerotic Progression Involving With Vascular Smooth Muscle Cell (VSMCs) Phenotypic Switching and Proliferation by PKM2-Mediated Glycolysis
Authors: Qi Yu
Journal: Circulation (2023)

Introduction: As a VEGF-targeting agent, sorafenib has been used to treat a number of solid tumors but can easily lead to adverse vascular effects, including hypertension, myocardiopathy and coronary artery spasm. Our previous study reveals that sorafenib impairs endothelium-dependent vasodilatation, whereas the effect of sorafenib on atherosclerotic progression has not been determined. Hypothesis: Hence, we hypothesize that sorafenib may promote atherosclerotic progression via such adverse vascular effects. Methods: ApoE -/- mice were orally administered by sorafenib for 12 weeks, indicating that sorafenib aggravates atherosclerotic progression via promoting the formation of foam cells and the accumulation of VSMCs in intima. To study the underlying mechanism, we used sorafenib to incubate VSMCs (0, 3 and 6 mg/L) for 48 h. Results: We found that sorafenib promoted the proliferation, migration and synthetic phenotype-related gene expression in VSMCs. More importantly, sorafenib increased lactate production, the extracellular acidification rate, PKM2 expression and PK activity in VSMCs. Interestingly, after deletion of PKM2 in VSMCs by AAV-CRISPR/Cas9 system, decreased lactate production and the extracellular acidification rate were found. Meanwhile, sorafenib-induced the proliferation, migration and phenotypic switching of VSMCs were suppressed. Conclusions: Sorafenib can aggravate atherosclerotic progression and smooth muscle cell phenotypic switching, which may be partly ascribed to PKM2-depended glycolysis.
Abstract 18630: Variance In Endocardial Voltage Between The Sinus Node And Other Bi-atrial Regions In Patients With Atrial Fibrillation
Authors: Viren Srivastava, Prasanth Ganesan, Jatin Goyal, Brototo Deb, Zahra Azizi, Sanjiv M Narayan
Journal: Circulation (2023)

Background: The mechanisms for atrial fibrillation (AF) are unclear but correlate with substrates such as low voltage and CHADS2VASc risk factors, which is a target for AF ablation after the recent ERASE trial. Experimental models of AF show that fibrosis increases near the sinus node, which may explain the link between AF and sinus node dysfunction. However, such data are less clear in patients without global mapping of all regions simultaneously. Hypothesis: We hypothesize that there is a difference in regional endocardial voltages in AF patients mapping globally, specifically between the sinus node and other atrial regions. Methods: We studied N = 57 patients undergoing AF ablation with bi-atrial global endocardial voltage data (19 females, LVEF 58 ± 1.5%). Electrograms were collected using 64 pole basket catheters in the right (RA) and left (LA) atrium for 1 minute. We used custom software to analyze 3D electroanatomic maps (NavX, Abbott, IL) for voltages in 3 predefined regions in the RA near and remote from the sinus node, and in the LA (Fig 1). Results: Patients exhibited lower voltages in the lateral RA (0.43 ± 0.05 vs 0.66 ± 0.06 mV; p &lt; 0.05), and the RA septum (0.46 ± 0.04 vs 0.66 ± 0.06 mV; p &lt; 0.05) compared to the sinus node, respectively. Patients also exhibited lower voltages in the lateral RA compared to the LA roof (0.43 ± 0.05 vs 0.57 ± 0.05 mV; p &lt; 0.05). The difference between the sinus node and the LA roof (0.66 ± 0.06 vs 0.57 ± 0.05; p &gt; 0.05) and other regions failed to reach significance. No difference between combined right atrial voltage and left atrial voltage was found. Differences were maintained for successive time windows over 1 minute. Conclusion: We observed consistent regional variations in atrial voltage in AF patients, and higher voltage in the sinus node than other regions. Future studies should determine if this underlies the link between AF and sinus node dysfunction, and if this varies in comorbidities such as diabetes mellitus.
Abstract 14320: The Utility of Zebrafish Cardiac Arrhythmia Model to Predict the Pathogenicity of <i>KCNQ1</i> Variants
Authors: Kenshi Hayashi, Yaowen DENG, Cui Shihe, Isao Kobayashi, Akihiro Nomura, Ryota Teramoto, KEISUKE USUDA, Jingjing Kobayashi-Sun, Yuya Tazaki, Ayana Sasaki, Takashi Kusayama, Toyonobu Tsuda, Hayato Tada, Takeshi Kato, Kenji Sakata, Noboru Fujino, Masakazu Yamagishi, Masayuki Takamura
Journal: Circulation (2023)

Introduction: Genetic testing for inherited arrhythmias and discriminating pathogenic or benign variants from variants of unknown significance (VUS) is essential for gene-based medicine. KCNQ1 is a causative gene of type 1 long QT syndrome (LQTS) and familial atrial fibrillation (AF), and approximately 30% of the variants found in type 1 LQTS are classified as VUS. Aims: We studied the role of zebrafish cardiac arrhythmia model in determining the clinical significance of KCNQ1 variants. Methods and Results: We generated homozygous kcnq1 deletion zebrafish ( kcnq1 del/del ) using the CRISPR/Cas9 technique and expressed human Kv7.1/MinK channels in kcnq1 del/del embryos. We dissected the hearts from the thorax at 72 h postfertilization and measured the transmembrane potential of the ventricle or the atrium in the zebrafish heart. Action potential duration was calculated as the time interval between peak maximum upstroke velocity and 90% repolarization (APD90). The APD90 of the kcnq1 del/del embryonic ventricle was 280 ± 47 ms (n = 63), which was significantly shortened by injecting KCNQ1 wild-type (WT) cRNA and KCNE1 cRNA (162 ± 28 ms, n = 34, P &lt; 0.01 vs. kcnq1 del/del ). A study of two pathogenic variants (S277L and T587M) and one VUS (R451Q) associated with clinically definite LQTS showed that the APD90 of kcnq1 del/del embryonic ventricles with mutant Kv7.1/MinK channels (292 ± 40 ms for S277L, n = 27; 297 ± 63 ms for T587M, n = 25; 218 ± 49 ms for R451Q, n = 29, respectively) was significantly longer than that of Kv7.1 WT/MinK channels (P &lt; 0.01). Regarding the pathogenic variant (S140G) associated with familial AF, the APD90 of the kcnq1 del/del embryonic atrium with mutant Kv7.1/MinK channel was 124 ± 21 ms (n=13), which was significantly shorter than that with Kv7.1 WT/MinK (148 ± 17 ms, n = 8, P &lt; 0.05 vs. kcnq1 del/del with S140G Kv7.1/MinK channel). Conclusions: Functional analysis using in vivo zebrafish cardiac arrhythmia model may be useful for determining the pathogenicity of both loss-of-function variants in patients with LQTS and gain-of-function variants in patients with familial AF.
Abstract 14287: Real-World Healthcare Resource Utilization Among Patients With Hypertension or Congestive Heart Failure and Comorbid Alcohol Use Disorder
Authors: Regina Grebla, Lauren Strand, Summera Qiheng Zhou, Xin Zhao, Allison Keshishian, Monica McClain
Journal: Circulation (2023)

Introduction: Excessive alcohol consumption has been associated with increased risk of cardiovascular (CV) disease. Hypertension (HTN) is a known risk factor for CV disease, in general, including congestive heart failure (CHF). Healthcare resource utilization (HRU) and costs associated with comorbid alcohol use disorder (AUD) among patients with HTN or CHF were evaluated. Methods: This retrospective cohort study identified adults with moderate-to-severe AUD from patients with ≥1 inpatient, or ≥2 outpatient claims on separate days, for HTN or CHF (MarketScan® and Medicare [1/1/2016-12/31/2020], Medicaid [1/1/2016-12/31/2019] databases), and ≥1 year of continuous healthcare enrollment prior to diagnosis (baseline) and 3 months after. Monthly HRU and costs were compared between propensity-score matched patients based on AUD presence using rate ratios in generalized linear models. Results: Of 4,015,785 patients with HTN, 1% were diagnosed with AUD. Use of HTN pharmacotherapy was similar for all patients, except for less frequent use of angiotensin receptor blockers (ARBs) in those with AUD. HTN patients with comorbid AUD had a higher risk of inpatient visits (89%), ED visits (39%), longer inpatient stays (98%), and outpatient visits (9%) relative to non-AUD patients. Of 294,892 patients with CHF, 2% had comorbid AUD. CHF pharmacotherapy use was similar for all patients, except for less frequent ARB use in those with AUD. CHF with comorbid AUD had a higher risk of inpatient visits (31%), ED visits (25%), and longer inpatient stays (34%) relative to non-AUD patients. Outpatient visits were 5% lower in CHF patients with AUD. AUD was associated with higher acute care costs, fewer pharmacy claims, and lower pharmacy costs in both HTN and CHF cohorts. Patients with AUD in both cohorts were more likely to be younger, male, enrolled in Medicaid, with a higher comorbidity burden. Conclusion: In this real-world study, the presence of AUD in patients with either HTN or CHF was associated with greater comorbidity burden, higher acute care utilization and costs, and lower outpatient pharmacy utilization relative to patients without AUD. These findings suggest that AUD impacts care for both HTN and CHF, which could be an opportunity for improved screening and treatment.
Abstract 16630: Economic Impact of Frailty in Patients Undergoing Elective Percutaneous Left Atrial Appendage Closure (LAAC) With WATCHMAN Device
Authors: Shivaraj Patil, Sahana Tito, Chaitanya Rojulpote, Viha Atri, Avica Atri, Abhijit Bhattaru, Ola Khraisha
Journal: Circulation (2023)

Introduction: Frailty is associated with significant morbidity and mortality in older adults. Currently, standard practice after percutaneous left atrial appendage closure involves monitoring patients overnight and discharging them the following day. Hypothesis: Frailty predicts increased hospital cost and length of stay (LOS) in patients undergoing elective LAAC with WATCHMAN device. Methods: Patients aged ≥65 years who underwent elective LAAC with WATCHMAN device were identified using ICD-10 procedure code 02L73DK from 2016-2018 HCUP-NIS Database. In-hospital major adverse event (MAE) was defined as the composite of mortality, stroke (ischemic or hemorrhagic) or TIA, bleeding or transfusion, vascular complications, myocardial infarction, systemic embolization, and pericardial effusion or tamponade requiring pericardiocentesis or surgery. Hospital Frailty Risk Score (HFRS) was calculated for each patient based on 109 ICD-10 diagnosis codes and classified into non-frail (HFRS &lt; 5) and frail (HFRS score ≥ 5) groups. Multivariate regression analysis was used to assess the relationship between the HFRS and hospital cost hospitalization (≥90 centile) and prolonged LOS (&gt;72 hours). Results: 28,050 patients (Age = 77.3 ± 6.4 years; Female = 42.6%) were included. Median hospitalization cost was $24,500 (inter-decile range: $14,000-37,100) and median LOS was 1 day (inter-decile range: 1-2 days) and 4.7% experienced in-hospital MAE. Frail patients (HFRS score ≥ 5) constituted 12.5% of the cohort. Increasing Hospital Frailty Risk Score was associated with a greater risk of high-cost hospitalization and LOS &gt; 72 hours (Figure). Conclusions: Increasing frailty is a significant predictor of increased hospital cost and LOS in elective LAAC. This effect is independent of age and in-hospital MAE.
Abstract 15358: Deletion of <i>Csf2</i> Accelerates Disease Progression in a Mouse Model of Arrhythmogenic Cardiomyopathy
Authors: Stephen P Chelko, Vinay Penna, Morgan Engel, Maicon Landim-Vieira, Ann Centner, Elisa N Cannon, Kory Lavine, Jeffrey E Saffitz
Journal: Circulation (2023)

Arrhythmogenic cardiomyopathy (ACM) is a familial heart muscle disease driven by persistent innate immune signaling. We have shown that ventricular fibrosis and contractile dysfunction in Dsg2 mut/ mut mice, a model of ACM with homozygous knock-in of a variant in the gene for the desmosomal protein desmoglein-2, is mediated by activation of NFκB and actions of pro-inflammatory macrophages that express CCR2. To gain further insights into the roles of specific immune signaling pathways in the pathogenesis of ACM, we crossed Dsg2 mut/ mut mice with mice with germline deletion of Csf2 which encodes GM-CSF. This factor acts to mobilize inflammatory cells to sites of injury. Csf2 -/- mice have a normal leukocyte repertoire and no apparent phenotype under basal conditions, but show reduced immune cell infiltration after MI associated with improved healing and cardiac function. Thus, we anticipated delayed onset and less severe disease in Dsg2 mut/ mut Csf2 -/- mice compared with Dsg2 mut/ mut mice. In fact, the opposite occurred. By 8-weeks of age, Dsg2 mut/ mut Csf2 -/- mice showed a marked increase in ventricular fibrosis (18.2±6.2% of section area; n=11; p&lt;0.05 vs all) compared to Dsg2 mut/ mut (2.6±0.4%; n=27) or wildtype (WT) control (0.9±0.1%; n=18) mice. Dsg2 mut/ mut Csf2 -/- mice also had reduced LV ejection fractions (49.6±8.3%; n=11; p&lt;0.05 vs all) compared to Dsg2 mut/ mut (64.5±3.2%; n=27) or WT (81.8±1.0%; n=18) mice. Hearts of 8-week Dsg2 mut/ mut Csf2 -/- mice contained increased levels of pro-inflammatory chemokines (CCL21, CXCL1), matrix metalloproteinases, osteopontin (Spp1) and periostin (Postn). Single nucleus RNA sequencing studies revealed increased numbers of Spp1 + macrophages and Postn + fibroblasts, and a marked decrease in cDC2 dendritic cells in hearts of Dsg2 mut/ mut Csf2 -/- mice compared to Dsg2 mut/ mut or WT mice. cDC2 dendritic cells are known to have anti-inflammatory actions. These results suggest that cDC2 cells, mobilized by GM-CSF, may act to mitigate disease onset and severity in ACM. If so, cDC2 cells could serve as a determinant of disease expression in ACM patients.
Abstract 12701: Safety and Tolerability of Angiotensin Receptor Neprilysin Inhibitor Initiation in High-Risk Acute Myocardial Infarction Relative to Drug Initiation Setting: A Subgroup Analysis of the PARADISE-MI Trial
Authors: Carmine De Pasquale, Brian Claggett, Karola Jering, John J McMurray, Douglas L Mann, Christopher Granger, Lars Kober, Eldrin F Lewis, Aldo Pietro P Maggioni, Jean L Rouleau, Scott Solomon, Philippe G Steg, peter van der meer, Eugene Braunwald, Marc A Pfeffer
Journal: Circulation (2023)

Background: The initiation of blood pressure lowering pharmacologic agents during an acute myocardial infarction (AMI) can be challenging. The PARADISE MI trial randomised AMI patients with LV dysfunction and/or pulmonary congestion to either sacubitril/valsartan or ramipril within 7 days of presentation. At the physician’s discretion, drug initiation occurred in the inpatient (IP), day of discharge (DD), or outpatient (OP) setting. Objectives: To explore the safety and tolerability of sacubitril/valsartan versus ramipril when initiated in AMI in the IP, DD or OP care setting. Methods: Efficacy (cardiovascular death or incident heart failure), safety and tolerability were compared across initiation settings, and by randomization to either sacubitril/valsartan or ramipril. Results: Compared to IP, both DD and OP groups had fewer poor prognostic characteristics. Furthermore, serious adverse events were less frequent in the DD and OP compared to IP cohorts. The efficacy of sacubitril/valsartan on the primary outcome did not vary. Although overall adverse event rates were similar within initiation setting cohorts, systolic BP was lower with sacubitril/valsartan, regardless of initiation setting. The increased relative risk of hypotension with sacubitril/valsartan was similar across initiation settings. Conclusion: In this analysis of the PARADISE-MI trial based on drug initiation setting, sacubitril/valsartan reduced BP compared to ramipril. However, the clinical setting of drug commencement did not impact adverse event or tolerability signals between sacubitril/valsartan and ramipril.
Abstract 287: Psychosocial and Functional Status Are Associated With Readiness for Hospital Discharge Among Cardiac Arrest Survivors
Authors: Alexander M Presciutti, Kate Flickinger, Patrick J Coppler, Cecelia Ratay, Ankur A Doshi, Sarah Perman, Ana-Maria Vranceau, Jonathan Elmer
Journal: Circulation (2023)

Introduction: Long-term cardiac arrest (CA) survivors have recounted feeling unprepared to confront the psychosocial, functional, and cognitive sequelae of CA, but this has not been assessed quantitatively. Hypothesis: Psychosocial, functional, and cognitive status are associated with readiness for discharge post-CA. Methods: We prospectively recruited CA survivors treated by the University of Pittsburgh Post-Cardiac Arrest Service (4/21-9/22) who completed study measures within 72 hours prior to hospital discharge. We used linear regression to examine unadjusted associations between potential covariates (sex, income, arrest location, Charlson Comorbidity Index, time to return of spontaneous circulation, initial rhythm), post-CA sequelae (emotional distress screen via PROMIS Depression and Anxiety Short Forms 4A or PTSD Checklist-5, functional status via modified Rankin Scale, cognitive status via Telephone Interview for Cognitive Status, and social support via ENRICHD Social Support Inventory) and our dependent variable (readiness for discharge assessed via Patient Readiness for Hospital Discharge Scale - Short Form). Covariates significant at p &lt; 0.10 were included in a multivariable regression. Results: We included 110 grossly cognitively intact CA survivors (mean age 59 years, 64% male, 88% non-Hispanic White, 48% low income, 36.4% emotionally distressed, 21.9% functionally dependent, 24.5% cognitively impaired). Emotional distress, functional dependence, and lower social support were associated with lower readiness for discharge (β’s [absolute value]: 0.23-0.31, p &lt; 0.01; R 2 = 0.34) after adjusting for CA location and Charlson Comorbidity Index. Cognitive status, demographic covariates, and other CA clinical characteristics were not associated with readiness for discharge. Conclusion(s): Psychosocial and functional status predict readiness for discharge in this sample of grossly cognitively intact CA survivors. Further research should focus on developing interventions targeted towards these domains prior to hospital discharge.