tbuckley/cabot-search huggingface dataset:
Abstract 4142376: Impact of Atrial Fibrillation on Outcomes in Patients with Esophageal Cancer Receiving Neoadjuvant Chemoradiation
Authors: Aravinthasamy Sivamurugan, Udhayvir Grewal
Journal: Circulation (2024)

Limited data indicate an elevated risk of atrial fibrillation (AF) after neoadjuvant chemoradiation in esophageal cancer however the role of AF as an independent predictor of outcomes post-esophagectomy remains under-studied. We sought to the impact of AF on overall outcomes of patients undergoing neoadjuvant chemoradiation and esophagectomy, with or without adjuvant nivolumab. The global TriNetX database was used to identify patients (based on ICD-10 codes) with esophageal squamous cell carcinoma or adenocarcinoma who received neoadjuvant chemoradiation with carboplatin and paclitaxel and subsequently underwent esophagectomy between 2009 and 2024. Patients who received adjuvant nivolumab were analyzed separately. Patients who developed AF were compared with patients who did not using propensity score matching (PSM) based on age, race, BMI, and multiple comorbidities. Outcomes over a 5-year period were mortality, ischemic stroke, and use of anticoagulation. Odds ratios with 95% confidence intervals were generated with generalized linear mixed modeling and a p value of &lt;0.05 was considered statistically significant. A total of 1007 patients were identified, of these 186 (18.5%) developed AF after esophagectomy. PSM yielded 94 pairs for patients without adjuvant nivolumab. In this group, mortality was not significantly higher in patients with AF [OR=1.409 (0.793-2.504), p=0.242]. Incidence of stroke was equivalent between patients with and without AF [OR=1 (0.396-2.528), p = 1], despite significantly higher use of anticoagulation in the AF group [OR= 2.004 (1.071-3.749), p&lt;0.028]. PSM for patients receiving adjuvant nivolumab yielded 68 pairs. In this cohort, AF was not associated with a significant difference in mortality [1.86 (0.843, 3.870), p = 0.126]. Incidence of stroke was significantly higher in patients with AF [Risk difference = 0.147 (0.063, 0.231) p = 0.0001], however anticoagulation use was not significantly higher in the AF group [1.944 (0.862, 4.384), p = 0.106]. The current analysis highlights a high incidence of AF after neoadjuvant chemoradiation in esophageal cancer. However, despite rigorous vetting with PSM, we found no difference in mortality associated with AF both among patients who received or did not receive adjuvant nivolumab. Diligent use of anticoagulation is required among patients with AF post-esophagectomy due to an increased risk of stroke. These findings merit confirmation in a large prospective cohort.
Abstract 4142521: A Heart Transplant Patient’s Mysterious Illness: A Diagnostic Odyssey
Authors: Mutaz Alkalbani, Hassan Nayer, ADAM COCHRANE, Ibrahim Saeed, Mitchell Psotka, Allman Rollins, Jamie Kennedy, Vanessa Blumer
Journal: Circulation (2024)

A 60-year-old male patient underwent orthotopic heart transplant for non-ischemic cardiomyopathy three years ago. Recently, he has been followed closely in transplant clinic for persistently elevated donor-derived cell-free DNA; endomyocardial biopsy was negative for allograft rejection. Cardiac MRI showed a global increase in T1 signal with normal T2 suggestive of nonspecific myocardial injury. He later presented with fever and diarrhea. Physical examination revealed pale conjunctivae, non-edematous extremities, and no jugular venous distension. Leukocyte count was 10.1 x10 3 /uL, hemoglobin 14 g/dL, platelets 407 x10 3 /uL, creatinine 1.2 mg/dL, AST 53 U/L, ALT 50 U/L, total bilirubin 0.7 mg/dL. Infectious disease workup was positive for norovirus, which was managed conservatively. He returned a week later with sudden right-sided weakness, confusion, and recurrent fever. Brain MRI was negative for acute pathology. Leukocyte count was elevated in the cerebral spinal fluid. No other etiology could be identified. Eventually, microbial cell-free DNA test was positive for toxoplasma gondii. Follow-up endomyocardial biopsy with hematoxylin and eosin stain confirmed diagnosis of toxoplasmosis. He was started on sulfadiazine, pyrimethamine, and folinic acid for six weeks. Follow up biopsy one month later was negative for toxoplasma gondii. Toxoplasmosis can be reactivated in immunocompromised individuals. Cardiac involvement is rare but can lead to myocarditis, pericarditis, or arrhythmias. Post-transplant toxoplasmosis is often due to transmission from the allograft rather than reactivation. Endomyocardial biopsy with special staining can help differentiate between infection and allograft rejection. Microbial cell-free DNA testing can also help isolate rare infectious etiologies, especially when other serum markers are inconclusive. This case illustrates: (1) the importance of differential diagnosis in post-transplant patients and the benefit of microbial cell-free DNA testing, (2) the need to consider various diagnoses in cases of elevated donor-derived cell-free DNA, (3) the necessity for increased awareness of Toxoplasma gondii infection in transplant patients with compatible symptoms, and (4) the crucial role of a multidisciplinary approach in delivering high-quality care in complex cases.
Abstract 4142607: Influence of Seasons on the Management and Outcomes of Pulmonary Embolism
Authors: Mridul Bansal, Aryan Mehta, Khansa Ahmad, Sreeram Yalamanchili, Lakshmi Subramanian, Jinnette Abbott, Saraschandra Vallabhajosyula
Journal: Circulation (2024)

Background: While previous studies have noted seasonal variation in acute cardiovascular conditions, such as higher myocardial infarction in the winter, there are limited data on the impact of seasonal variations in pulmonary embolism (PE) outcomes. Methods: All adult (greater than or equal to 18 years) non-elective admissions with a primary diagnosis of PE with available data on the month of admission were identified using the National Inpatient Sample (2016-2020). We stratified the seasons into spring (March-May), summer (June-August), fall (September-November), and winter (December-February). Outcomes of interest included in-hospital mortality, total hospitalization costs, hospital length of stay, and discharge disposition. Results: During 01/01/2016 to 12/31/2020, 903,254 PE admissions with were identified. Spring, summer, fall, and winter had 23.9%, 25.1%, 25.2%, and 25.5% admissions, respectively. Admissions during the four seasons were comparable on sex distribution. Spring had higher admissions of white race (spring 69.6%, summer 68.8%, fall 68.9%, winter 69.2%) whereas summer had highest black race admissions (spring 18.3%, summer 19.0%, fall 19.0%, winter 18.6%) and those in lowest socioeconomic quartile (spring 28.2%, summer 28.7%, fall 28.5%, winter 28.1%) (all p &lt;0.05). Respiratory failure was the highest in winter (spring 26.2%, summer 25.7%, fall 26.4%, winter 26.8%), whereas renal failure (spring 13.4%, summer 13.7%, fall 14.2%, winter 13.9%) bleeding complications (spring 5.7%, summer 5.8%, fall 6.1%, winter 5.9%), were higher in fall (all p&lt;0.05). Mechanical thrombectomy rates were highest in fall (spring 1.0%, summer 1.3%, fall 1.7%, winter 1.2%, p&lt; 0.001), whereas systemic thrombolysis (spring 2.8%, summer 3.2%, fall 3.1%, winter 3.1%, p=0.02) was highest in the summer. Use of catheter directed therapies was comparable. There were no difference in-hospital mortality rates among seasons but winter had highest length of stay, lowest discharges to home, and fall had highest hospitalization costs. Conclusion: In this five-year study duration, despite some differences in organ failure and complication rates, there was no significant seasonal variation in the in-hospital mortality from PE. Winter months had the highest in-hospital resource utilization.
Abstract 4142190: Patient-Reported Health Status Among Patients with Heart Failure with Improved Ejection Fraction
Authors: Elena Vasti, Jimmy Zheng, Neil Kalwani, Colette Dejong, Ankeet Bhatt, Andrew Ambrosy, Natasha Din, Paul Heidenreich, Alexander Sandhu
Journal: Circulation (2024)

Introduction: The prevalence of heart failure with improved ejection fraction (HFimpEF) is growing. The association of ejection fraction recovery and changes in health status has not been previously reported. Hypothesis: We hypothesized patient-reported health status (HS) will be significantly better among patients with HFimpEF compared with those with HF with reduced ejection fraction (HFrEF) or HF with mid-range/preserved ejection fraction (HFmrEF/HFpEF). Methods: We identified patients with HF with at least 2 encounters with the Stanford cardiology clinic who completed a routinely collected Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 from 8/2020 to10/2023. HFimpEF was defined as most recent EF&gt;40% from a preceding echocardiogram &gt; 30 days prior with EF &lt; 40%. We compared patient sociodemographic and clinical characteristics across EF classifications. We analyzed KCCQ-12 Overall Summary Score (OSS) across EF classifications with and without adjustment for patient characteristics via multivariable linear regression, from which we calculated the R 2 to determine the impact of clinical characteristics on variation in HS among patients with HFimpEF. Results/Data: A total of 2,519 patients were included in this analysis, of which 18.7% had HFimpEF, 55.7% had HFmrEF/HFpEF, and 25.6% had HFrEF. Median KCCQ-12 OSS was 80.3, 73.9, and 80.8 for HFimpEF, HFrEF and HFmr/HFpEF patients, respectively. Patients with HFimpEF were less likely to be women compared with patients with HFmrEF/HFpEF (41% vs 58%, p&lt;0.01). There was substantial overlap in the KCCQ-12 OSS across EF classifications ( Figure ). KCCQ-12 OSS score was 5.2 points lower among patients with HFrEF compared with patients with HFimpEF [(95% CI: -8.2 to -2.3); p=0.01] but patients with HFimpEF had similar scores to those with HFmrEF/HFpEF [-1.1 (95% CI: -3.7 to 1.6); p=0.43]. Among patients with HFimpEF, a multivariable regression model explained 16% of the variation in the KCCQ-12 OSS. Conclusions: Despite improvement in EF, patients with HFimpEF continue to have impaired HS that is similar to patients with HFpEF and HFmrEF. Further research is needed to better understand impaired HS and to identify interventions to improve health status among patients with HFimpEF.
Abstract 4142364: Active Left Atrial Ejection Fraction as a Non-Invasive Prognostic Marker in Left Heart Failure associated Pulmonary Hypertension
Authors: Di Zhou, Li Xin, Zhihong Liu, Minjie Lu
Journal: Circulation (2024)

Background: Patients with left heart failure (LHF) associated pulmonary hypertension (PH) exhibit a complex pathophysiological progression and poor prognosis. The current study aims to explore the non-invasive prognostic metrics in this population. Methods: In this retrospective study, consecutive patients who diagnosed with LHF associated PH and underwent cardiac magnetic resonance (CMR) imaging between December 2010 and December 2021were included. The endpoint were adverse events, including all-cause death, heart-lung transplantation, or left ventricular assist device implantation. Results A total of 174 patients with LHF associated PH were included in the study, and the average age of the population were 53.2 ± 14.9 years. After a median follow-up of 31.9 months, 58 patients experienced adverse events. Pulmonary artery wedge pressure had a moderate correlation with active left atrial ejection fraction (LAEF) (r = -0.397, p = 0.044). Active LAEF had a significant correlation with oxygen consumption at anaerobic threshold (r = 0.769, p &lt; 0.001) and peak oxygen consumption (r = 0.754, p &lt; 0.001). After adjusting for confounders, active LAEF can independently predict adverse events, beyond the echocardiography and other CMR variables under consideration (C-statistic: 0.773). Among HF patients with preserved ejection fraction, those with active LAEF ≤ 8.6% had a 7.046-fold higher risk of experiencing the composite endpoint compared to those with active LAEF &gt; 8.6%. Conclusions: Active LAEF is worthy of consideration for evaluating disease severity and predicting prognosis in patients with LHF associated PH. The integration of active LAEF and HF subtypes can further identify patients with different risk profiles.
Abstract 4142224: Efficacy of Inferior Vena Cava-Pulmonary Artery Bypass for Right Ventricular Dysfunction under Left Ventricular Assist Device Support: An in vitro study using a biventricular circulation system
Authors: Kanami Uchida, Kaoru Hattori, Hitoshi Inafuku, Takada Jumpei, Kojiro Furukawa, Kiyotaka Iwasaki
Journal: Circulation (2024)

Introduction: Right heart failure under the support of a left ventricular assist device (LVAD) presents a life-threatening condition characterized by organ edema and limited LVAD support. Implementing an inferior vena cava-pulmonary artery (IVC-PA) bypass graft may mitigate these complications by reducing central venous pressure (CVP) and improving LVAD support efficiency. This study aimed to elucidate an adequate graft diameter for an IVC-PA bypass in terms of CVP reduction during LVAD-assisted circulation using an in vitro biventricular pulsatile circulatory system. Methods: We developed a biventricular pulsatile circulation system capable of providing circulatory assistance via an LVAD (centrifugal pump) connected to the apex of a left ventricular model （Fig）. A representative condition of cardiogenic shock was produced by adjusting LV systolic pressure, aortic pressure, and CVP to 80 mmHg, 80/40 mmHg, and 7.5 mmHg, respectively. A right heart failure model was produced by adjusting LV systolic pressure, aortic pressure, and CVP to 45 mmHg, 70 mmHg, and 16 mmHg, respectively, under LVAD support at 1700 rpm. Then, an adequate IVC-PA bypass diameter was investigated in terms of reducing CVP and increasing bypass flow support among 4mm and 18 mm with 2mm interval. The diameters of PA and IVC, and systolic PA pressure were set to 19 mm, 19 mm, and 18 mmHg, respectively. Elastic LV and RV models were driven by pneumatic positive and negative pressures. Results: We found a linearly increasing trend of bypass flow and a decreasing trend of CVP with increasing bypass diameters from 4 to 12 mm. When applying the bypass graft over 12mm diameter, bypass flow and CVP plateaued at 3.4 L/min and 7.5 mmHg, respectively (Fig). Conclusion: Our sophisticated in vitro biventricular circulation study suggests that in scenarios of right heart failure under LVAD support, implementing a bypass graft from the IVC to the PA is effective for decreasing CVP and reducing right ventricular preload. This study indicates that the optimal bypass diameter for reducing CVP is 12 mm when the diameters of the IVC and PA are 19 mm. These findings encouraged us to evaluate the efficacy in in vivo clinical settings.
Abstract 4142380: Random survival forests identify myocardial gene signatures associated with survival in heart failure with preserved ejection fraction
Authors: Suraj Kannan, Hildur Knuttsdottir, Joban Vaishnav, Joel Bader, David Kass, Kavita Sharma, Virginia Hahn
Journal: Circulation (2024)

Background: Heart failure with preserved ejection fraction (HFpEF) continues to be poorly understood at the molecular level. While previous studies have identified gene expression signatures unique to HFpEF, genes associated with clinical decompensation have not been determined. Here, we performed exploratory analysis of myocardial RNA-seq data to identify genes associated with event-free survival in HFpEF. Methods: We analyzed previously published RNA sequencing data of right ventricular septal endomyocardial biopsies from HFpEF patients (n=41) with paired clinical, echocardiographic, and outcome data (including mortality and heart failure hospitalizations). We constructed random survival forests with forward stepwise regularization (the “variable hunting” method) to determine genes associated with time to first event using a combined end-point of heart failure hospitalization or all-cause death. Selection of candidate forest variables was tested with both random and weighted sampling methods. Results: We identified 33 genes that are predictive of survival in HFpEF (Figure 1A). This set includes genes previously implicated in heart failure, including ADAMTSL2 , ADRB1 , BMP6 , and METRNL . Patients with HFpEF were categorized into 3 groups (Gene Group) based on their expression of this survival gene signature. Gene Group 1 had the worst survival compared to Gene Groups 2 and 3 (log rank p values 7.85e-5 for Gene Group 1 vs 2, 1.16e-5 for Gene Group 1 vs 3, adjusted for age, sex, and renal function, Figure 1B). Survival was not significantly different between Gene Groups 2 and 3 (adjusted log-rank p value 0.17). Survival forests constructed using these genes outperform those constructed from clinical and hemodynamic parameters alone (out-of-bag C-index 0.894 vs 0.545). Moreover, in survival forests constructed from both gene data and hemodynamic measurements, individual survival genes consistently showed higher variable importance than clinical/hemodynamic parameters (Figure 1C). Conclusions: Random survival forests identify myocardial gene signatures that may better model HFpEF prognosis than clinical measurements. Further studies are warranted to validate findings in independent cohorts.
Abstract 4142556: Incremental Value of Multiparametric Cardiac MRI for Non-invasive Identification of Significant Acute Cardiac Allograft Rejection: a Prospective and Biopsy-proven Study
Authors: Pengyu Zhou, Shihua Zhao
Journal: Circulation (2024)

Background: Multiparametric cardiac magnetic resonance (CMR) serves as the gold standard for evaluating cardiac structure and function in vivo, and allows assessing myocardial tissue characterization non-invasively, providing a potential alternative for identifying significant acute cardiac allograft rejection (SR). Aims: This study aimed to evaluate the association between CMR multiparameters and SR, and assess the incremental value of CMR multiparameters over conventional serum examinations for identifying SR using the likelihood ratio analysis. Methods and results: Heart transplantation (HTx) recipients with endomyocardial biopsy and healthy controls were prospectively recruited for CMR assessment. CMR feature tracking (CMR-FT) was performed to evaluate the left ventricular (LV) global strain in all three directions. The last serum examinations including N-terminal pro brain natriuretic peptide (NT-proBNP) before anti-rejection therapy were recorded. Participants were divided into 3 groups based on biopsy grade: control, SR (acute cellular rejection [ACR] grade≥2R and/or antibody-mediated rejection [AMR] grade≥pAMR1), and NSR (ACR grade&lt;2R and AMR grade=pAMR0). Finally, thirty controls (43.3±13.6 years, 26 male) and 51 HTx recipients comprising 23 SRs (48.6±12.6 years, 24 male) and 28 NSRs (42.7±14.9 years, 16 male) were enrolled for analysis. Compared with NSRs, SRs showed elevated NT-proBNP (7797.0±7527.6pg/ml vs 3334.6±5935.3pg/ml, p&lt;.001), worse LV global longitudinal strain (GLS) (-9.7±3.1% vs -13.1±2.9%, p&lt;.001), and increased native T1 (1384±80.1ms vs 1321±69.9ms, p&lt;.001) and T2 values (50.9±2.7ms vs 45.7±4.3ms, p&lt;.001). In multivariable analysis, LVGLS (OR=0.76, 95%CI, 0.59 to 0.98, p=.03) and T2 value (OR=1.35, 95%CI, 1.10 to 1.65, p=.01) were independently associated with SR after NT-proBNP adjustment. Furthermore, the likelihood ratio test showed LVGLS (p=.002) and T2 value (p&lt;.001) had incremental value over NT-proBNP for identifying SR. Conclusion: LV GLS and T2 value were independently associated with SR, providing incremental value for non-invasive identification of significant rejection in HTx recipients.
Abstract 4142394: HDL/ApoA1 inhibits macrophage ferroptosis via upregulating NRF2/SLC7A11/GSH pathway
Authors: Yonghong Luo, Yuting Yi, Yongjie Deng, Daoquan Peng
Journal: Circulation (2024)

Background: Ferroptosis is a novel type of programmed cell death characterized by excessive lipid peroxides and iron overload inside the cell. SLC7A11/GSH is one of the most important anti-ferroptotic pathways. Macrophage ferroptosis contributes to the progression of atherosclerosis. HDL exerts anti-atherosclerotic effects primarily by promoting cholesterol efflux. Whether HDL also inhibits macrophage ferroptosis is unknown. Research Questions: This research was aimed to explore the effects and mechanisms of HDL on macrophage ferroptosis. Methods: Macrophage ferroptosis was detected in plaques from patients with coronary artery disease. In vitro, macrophage was induced ferroptosis by multiple inducers and then the cells were treated with either vehicle or HDL or ApoA1. Ferroptosis was measured by detecting multiple ferroptosis markers (lipid peroxide, LDH release, ROS production, and cellular ferrous ion level). Results: Compared to controls, iron, lipid peroxide and macrophages were co-localized and significantly increased in coronary plaques, suggesting increased macrophage ferroptosis in atherosclerosis. In mouse macrophages, ferroptosis-inducers increased ferroptosis significantly, which was inhibited by HDL and ferroptosis inhibitors, but not neither by inhibitors of apoptosis, necroptosis, or autophagy. ApoA1, the main apolipoprotein on HDL, may account for HDL’s anti-ferroptotic effect. Mechanically, ApoA1 upregulated System Xc- (encoded by SLC7A11), an amino acid antiporter that exchanges intracellular glutamate and extracellular cysteine, thus elevating intracellular GSH and reducing ferroptosis. We further elucidated that ApoA1 activated NRF2, the transcription factor of SLC7A11, by promoting its nuclear translocation. Conclusion: Our results imply that HDL/ApoA1 inhibits macrophage ferroptosis via upregulating NRF2/SLC7A11/GSH pathway, enriching the regulation and mechanisms of HDL/ApoA1’s anti-atherosclerotic effects.
Abstract 4142312: 90-Day Readmission Rates, Predictors, and Causes of Readmission After Placement of Left Atrial Appendage Occlusion Device in Patients With history of different malignancies: National Readmission Database analysis
Authors: Andres Quevedo Ramirez, Taha Teaima, Vivek Jha, Joshua Ibarra, Raquel Soon-Shiong, Javier Gomez Valencia
Journal: Circulation (2024)

Introduction: Patients with cancer have a higher risk for both arterial and venous thromboembolism. Furthermore, this population subset has an increased risk of bleeding when treated with anticoagulation. Left atrial appendage occlusion devices (LAAODs) have emerged as an alternative to oral anticoagulation in patients at high risk for bleeding events. There is a paucity of data regarding the efficacy of LAAODs in cancer patients. In our study, we investigated the readmission rates, predictors, and causes of readmission after LAAODs placement in patients with underlying malignancy. Methods: The National Readmission Database for 2016, 2018, and 2020 was queried to identify hospitalized adults for LAAOD placement with a history of cancer. Multivariate logistic and linear regression analyses were used to adjust for possible confounders. Results: A total of 566 patients were hospitalized for LAAOD placement and had a history of different malignancies with 563 discharged alive. Within 90 days from discharge, 141 patients (25%) were readmitted. Exacerbation of Congestive heart failure (CHF) (7.9%), Sepsis (6.7%), Lower GI bleeding (4.3%), Iron deficiency anemia (3.8%), unspecified gastrointestinal hemorrhage (3.1%), and paroxysmal Atrial fibrillation (2.6 %) were most common causes of readmissions. Independent predictors of readmission included female sex (aOR 1.68, 95% CI: 1.07 – 2.63, P=0.022), acute kidney injury (aOR 4.6, 95% CI: 1.5-8.4, P=0.008), and anemia (aOR 1.71, 95% CI: 1.08-2.7, P=0.023). Conclusion: Predictors of readmission included female sex, anemia, and acute kidney injury during index admission. The most common causes of readmission included Exacerbation of CHF, Sepsis, Lower GI bleeding, and Iron deficiency anemia. Addressing readmission causes and predictors is needed to prevent such a high rate of readmissions after LAAODs placement in cancer patients.