tbuckley/cabot-search huggingface dataset:
Abstract 4140638: CARDIAC TUMORS EVOLUTION IN PATIENTS WITH TUBEROUS SCLEROSIS
Authors: Viviane Hotta, Anna Christina Ribeiro, Maria Rosa Quadro Matos, Ana Cristina Tanaka, Marilia Soliani, Gardenia Oishi, Ruiza Rocha, Nana Miura, Fabio Fernandes
Journal: Circulation (2024)

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease characterized by the formation of benign tumors located mainly in the central nervous system, skin, kidneys, heart, eyes and lungs . It is estimated that 70% to 90% of rhabdomyomas (the most prevalent cardiac tumors in the pediatric population) are related to TSC. Most cardiac tumors regress spontaneously during the first year of life. However, there are reports of recurrence, suggesting the possibility of hormonal influence. Purpose: To perform a descriptive study of clinical variables, with a cardiological focus, electrocardiographic, echocardiographic and cardiac magnetic resonance imaging characteristics, in addition to the treatment and clinical evolution of patients diagnosed with TSC treated over 24 years of follow-up. Methods: A retrospective, descriptive study will be carried out at the Clinical Unit of Cardiomyopathies and Congenital Heart Diseases of InCor/FMUSP. Data was collected from the institution's electronic medical record from January 1997 to January 2021. Patients with a clinical and or genetic diagnosis of TSC were selected. Analysis of clinical, electrocardiographic, echocardiographic and CMR variables were performed. Death and the need for surgical treatment will also be evaluated. Data from the first and last TTE and CMR available in the system were analyzed. Results: 77 patients with TSC diagnosis were included, 47 (61%) patients were females. The mean age of the patients was 24 ± 15.1 years. The majority of patients (N = 67; 87%) self-reported white ethnicity. 50 patients had cardiac tumors, 49 patients had rhabdomyomas (RM) and 1 patient presented with pericardial lipoma. Between the patients with RM, 15 (30%) had single tumors and 35 (70%) patients had two or more tumors. Regarding clinical evolution, 39 patients (78%) presented incomplete involution, 9 patients (18%) complete regression and 1 patient presented an increase in the mass. Surgical treatment was necessary, at some point, in 4 (8%) patients and 2 (4%) patients died during the postoperative period. There is no record of heart transplantation. Conclusions: Regarding clinical variables, 64% of the patients had cardiac tumors. Most patients were asymptomatic, only (4%) had complex ventricular arrhythmias. Most patients had multiple LV or biventricular rhabdomyomas assessed by TTE or CMR. The majority of patients (78%) had incomplete involution of rhabdomyomas in 24 years of follow-up.
Abstract 4140642: Comparative Analysis of Prodromal Symptoms in Head-Up Tilt Test vs. Spontaneous Vasovagal Syncope
Authors: Mohammadreza Babaei, Mehdi Mehrani, Hamed Tavolinejad, Ali Bozorgi, Saeed Sadeghian, Ali Vasheghani Farahani, Somaye Yadangi, Arya Aminorroaya, Masih Tajdini
Journal: Circulation (2024)

Background: The diagnosis of VVS largely relies on clinical history and simple diagnostic tools (e.g., electrocardiogram) to rule out dangerous differential diagnoses. However, using the head-up tilt test (HUTT) has become controversial among clinicians. This retrospective study aims to evaluate whether the prodromal symptoms experienced during HUTT are consistent with those experienced during spontaneous syncope. Methods: This study utilized data from the HUTT registry at the Syncope Unit of the tertiary Heart Center, focusing on adults aged 18 and older diagnosed with VVS. Diagnoses were based on clinical histories, physical examinations, and the latest syncope guidelines. Out of 1914 patients with HUTT results, 764 patients with positive tests were analyzed for mutual prodromal symptoms during HUTT and spontaneous syncope. Results: The McNemar test revealed significant differences for several symptoms, including palpitation (X2 = 30.59, P &lt; 0.001), nausea (X2 = 16.13, P &lt; 0.001), chest pain (X2 = 24.32, P &lt; 0.001), abdominal discomfort (X2 = 22.33, P &lt; 0.001), flushing (X2 = 10.87, P &lt; 0.001), and aura (X2 = 19.86, P &lt; 0.001), indicating discrepancies in the occurrence of these symptoms. Cohen's Kappa values ranged from 0.06 to 0.32, signifying slight to fair agreement. Specifically, diaphoresis (k = 0.32), palpitation (k = 0.27), and vertigo (k = 0.25) demonstrated fair agreement, whereas nausea, aura, chest pain, abdominal discomfort, and flushing exhibited slight agreement. Among the 640 patients who experienced prodrome during spontaneous syncope, 110 (17.19%) had no symptoms. Conversely, among the 123 patients who did not experience prodrome, 96 (78.05%) experienced at least one symptom during the tilt test (Figure). Conclusion: The assessment of prodromal symptoms during HUTT compared to spontaneous syncope showed significant differences for several symptoms and overall low levels of agreement. Also, tilt cannot differentiate patients with or without prodrome during their spontaneous spells.
Abstract 4141319: Enhancing Prognostic Prediction in STEMI Patients: The Incremental Value of Computational Pressure-Fluid Dynamics Applied to Index of Microcirculatory Resistance
Authors: Yang Duan, Junyi Zhang, Yafeng Zhou
Journal: Circulation (2024)

Background: The computational pressure-fluid dynamics applied to index of microcirculatory resistance, derived from coronary angiography (CPFD-caIMR) is a promising alternative method of IMR to evaluate the prognosis of STEMI patients. This study aim to evaluate the incremental value CPFD-caIMR and MVO in predicting MACE after patients with undergoing primary percutaneous coronary PPCI. Methods: A total of 292 patients who met the inclusion criteria were selected retrospectively from 1107 STEMI patients from January 2019 to January 2021 in Affiliated Hospital of Xuzhou Medical University in China. All patients with STEMI underwent CPFD-caIMR and MVO assessment. The patients were categorized into four groups based on CPFD-caIMR and MVO presence: 1) CPFD-caIMR ≤40U without MVO; 2) CPFD-caIMR &gt;40U without MVO; 3) CPFD-caIMR ≤40U with MVO; and 4) CPFD-caIMR &gt;40U with MVO. The primary endpoint of the study was MACE, defined as cardiovascular or all-cause deaths, non-fatal MI, revascularization including target vessel reconstruction, heart failure readmission. Results: Within the included 292 patients, a notable proportion of 101 cases (34.6%) revealed discrepancies between CPFD-caIMR and MVO. Among these, 103 patients (35.3%) exhibited CPFD-caIMR values of ≤40 without MVO, while 88 patients (30.1%) displayed CPFD-caIMR values of &gt;40 with MVO on CMR. Both MVO (HR: 2.750, p=0.033) and CPFD-IMR&gt;40U (HR: 3.572, p=0.001]) were predictors of MACE over 12 months. Specifically, for every 1-unit increase in CPFD-IMR&gt;40U, MACE increased by 3.572 units. Furthermore, ROC curve analysis demonstrated that CPFD-caIMR&gt;40U (AUC, 0.724, p＜0.001) and MVO (AUC, 0.667, p=0.001) were effective in predicting MACE. Notably, combined CPFD-caIMR and MVO increased the area under the curve for MACE to 0.820, p&lt;0.001). Over 12 month of follow-up, Group 4 (HR: 8.765, p &lt;0.001) but not Group 3 (HR: 3.474, p=0.029), Group 2(HR:3.554, p=0.045) had worse clinical outcomes compared with those with no significant CMD in Group 1. Conclusion: CPFD-caIMR is a novel method for noninvasive detection of microvascular reperfusion failure, and CPFD-caIMR &gt; 40U can predict the prognosis of STEMI patients.When combined with CMR, CPFD-caIMR &gt; 40U can be used to further stratify the risk of STEMI and to identify high-risk patients who may require more aggressive treatment during follow-up.
Abstract 4141243: All That Blocks is Not Clot: A Case of Left Ventricular Assist Device Obstruction from Extrinsic Compression
Authors: Jamnius Waller, Suyu Zhang, Veena Agusala, Nicole Guynn, Timothy Fernandez, Tamer Attia
Journal: Circulation (2024)

Description of Case: A 36-year-old male with a history of non-ischemic cardiomyopathy status post HeartMate 3 left ventricular assist device (LVAD) presented with a 2-day history of dizziness, lightheadedness, chest pain, and an increase in low flow alarm frequency from his LVAD. On admission, his temperature was 37.2, return to flow was 86, oxygen saturation was 100% on room air, heart rate was 99, and respiratory rate was 23. His lungs were clear to auscultation, and his abdomen was distended, tense, and non-tender. His extremities were warm, with moderate edema in his legs bilaterally. He had mild increased work of breathing without accessory muscle uses. Laboratory evaluation revealed a prothrombin time of 2.6 seconds, a B-type natriuretic peptide level of 176 pg/mL, and a hemoglobin of 13.7 g/dL. Imaging revealed a chest CT demonstrating a complete obstruction of the distal outflow cannula near its attachment to the aorta. Patient hemodynamics worsened after admission, necessitating transfer to the cardiac intensive care unit. After an unsuccessful attempt at warfarin reversal and tissue plasminogen activator administration, the patient was eventually taken for surgical intervention with cardiothoracic surgery. During the procedure, there were no signs of outflow graft thrombus; instead, a sizeable peri-graft fluid collection was observed and drained, which relieved the outflow graft obstruction. The patient’s post-operative course was uneventful, and he was eventually discharged home with a resolution of his symptoms. Discussion: This patient's presentation presents a few key features that suggest an alternative cause of an outflow obstruction other than an acute thrombus. The most important feature is that the patient had been diligent with his anticoagulation to indicate his being a therapeutic prothrombin time on admission, consistent with the patient's reported anticoagulation adherence. We believe that cases such as this one provide clinical support for the reevaluation of the way we approach outflow tract obstructions in LVADs; especially as we continue to develop devices that have lower thrombus risk that their predecessors. We hope that this patient’s clinical presentation and course will be helpful in the future differentiation of intrinsic vs extrinsic compression of LVAD cannulas and the management of such obstructions.
Abstract 4141227: Characterization of NIMA-related kinase 7 (NEK7)-NLRP3 inflammasome complex in macrophages by combining CRISPR/Cas9 gene-editing with comprehensive proteomic
Authors: Yuto Nakamura, Sarvesh Chelvanambi, Taku Kasai, Mary Whelan, Yusuke Sasaki, Sasha Singh, Elena Aikawa, Masanori Aikawa
Journal: Circulation (2024)

Background: The aberrant activation of the NLRP3 inflammasome in macrophages promotes chronic inflammation in cardiovascular disease (CVD). NEK7 is essential to the NLRP3 inflammasome’s function, however, its role in inflammasome-mediated macrophage activation has yet to be elucidated. Methods&amp;Results: We employed CRISPR/Cas9 gene editing to delete NEK7 in human primary macrophage cells (PBMCs) and in a macrophage-like cell line (THP-1). First, we employed mass spectrometry-based proteomics to monitor the response of Scramble control (ΔScr) or NEK7-null (ΔNEK7)-THP-1 cells to monosodium urate crystal (MSU). We quantified 4,030 proteins representing ΔNEK7-THP-1 and ΔScr-THP-1 conditions, analyzed at 4 timepoints (0hr, 1hr, 3hr, 6hr; MSU treamtent). NEK7 was identified in ΔScr but not in ΔNEK7 cells. In order to identify proteins whose abundances were suppressed by ΔNEK7, we performed a multiplexed high-dimensional clustering and network analysis using our custom made software ( XINA , Fig.A). Specifically, we identified NOD-like receptor and Interleukin-1 (IL-1) signaling in clusters 16 and 17, that a) increased steadily over the timepoints and b) were overrepresented by proteins from the ΔScr condition (Fig.A, red rectangles). Whereas in ΔNEK7, these proteins migrated to either clusters 3, 5, 25, or 35 (Fig.B, alluvial plot), indicating their suppression (Fig.A, blue rectangles). In ΔNEK7-PBMCs, IL-1β secretion decreased in response to MSU compared to ΔScr-PBMCs (Fig.C, n=8); and less chemotaxis as determined by high-content imaging that monitored PBMC migration (Fig.D, n=6). Finally, we confirmed that small molecule inhibitor of the NLRP3-NEK7 complex itself decreased IL-1β secretion in an MSU-elicited peritonitis mouse model (C57BL/6J, n= 8, Control: PBS, p&lt;0.05). Conclusions: NEK7 itself is sufficient as a therapeutic target to suppress inflammasome-mediated macrophage activation; providing molecular bases for the development of new therapies for CVD.
Abstract 4140970: Association Between Prescription Fill Rates and Adverse Outcomes within an mHealth Clinical Trial Designed to Improve Medication Adherence
Authors: Mallette Asmuth, Patrick Hosokawa, Larry Allen, Pamela Peterson, Mary Plomondon, Lisa Caputo Sandy, Shawni Vaughn, Joy Waughtal, Joel Marrs, Steven Orlando, Joseph Saseen, Richard Blankenhorn, Sheana Bull, Michael Ho
Journal: Circulation (2024)

Background: Medication nonadherence is associated with adverse outcomes in observational studies. However, whether that association persists in a clinical trial designed to improve adherence is uncertain. Question: We describe factors associated with low adherence among patients enrolled in a mHealth intervention utilizing text messages to improve cardiovascular (CV) medication refills. The relationship between adherence and adverse outcomes was then assessed. Methods: The NUDGE study was a pragmatic clinical trial randomizing patients to usual care versus different types of text messages (generic, behavioral nudge, behavioral nudge plus an AI chatbot) to improve refill rates when patients had a 7-day delay in a CV medication refill. For the current analysis, the primary exposure of low adherence was determined from pharmacy data and was defined as a proportion of days covered by medication (PDC, as calculated by prescription fill data) ≤0.80 in the first 3 months after enrollment. Adverse outcomes were defined as time to emergency department visit, hospitalization or death. The association between low adherence and adverse outcomes was evaluated using Cox proportional hazards models. Results: Of the 9268 patients enrolled in the study with prescription fill data, the median PDC was 0.74 (0.19-0.96, 25%-75% percentile). Patients with low adherence comprised 53.5% of the cohort. In this clinical trial, all 3 text messaging intervention arms increased refill adherence at similar rates (~5%) at 3-months compared to usual care. In multivariable analyses, low adherence in the first 3 months was associated with adverse outcomes (HR 1.13; 95% CI 1.06-1.19) regardless of study arm enrollment. Conclusion: Among patients enrolled in a randomized clinical trial to improve medication refill adherence, low adherence remains common and was associated with adverse outcomes. While this mHealth intervention increased CV medication refills, additional solutions are needed to improve medication adherence.
Abstract 4141025: Interleukin-22 Prevents Right Ventricular Remodeling and Tricuspid Regurgitation during Pressure Overload through a Unique Mechanism
Authors: Kodai Shibao, Hideo Yasukawa, Daiki Akagaki, Kota Okabe, Toshiyuki Yanai, Shima Kanako, Mai Yamamoto, Yoshihiro Fukumoto
Journal: Circulation (2024)

Introduction: Right ventricle (RV) remodeling is associated with prognosis in patients with RV failure. Interleukin-22 (IL-22) is a member of the IL-10 cytokine family, play roles in tissue protection and wound repair. We have previously shown that IL-22 plays an important role in left ventricular remodeling after acute myocardial infarction; however, the role of IL-22 in the development of RV remodeling remains elusive. Hypothesis: IL-22 would inhibit the development of RV remodeling during pressure overload. Methods: Pulmonary artery banding (PAB) is performed by placing a 6-0 suture around the pulmonary artery over a 24 G needle in wild type mice (C57BL/6J) and IL-22 knockout mice (IL-22 KO). Only mice with moderate pulmonary artery stenosis (peak pressure gradient across the pulmonary band&gt; 25 mmHg at 1 week after surgery by echo Doppler) were included in the study protocol. Four weeks after PAB, RV function was measured by echocardiography and transcriptome analysis was performed on mRNA samples isolated from the RV and differentially expressed genes were identified by EdgeR (p&lt;0.05). Survival confirmation of mice with moderate pulmonary artery stenosis was also performed up to 56 days. Results: IL-22 KO mice had significantly higher 56-day mortality rate compared with WT mice after PAC (p&lt;0.01). Four weeks after PAB, IL-22 KO mice showed markedly increased RV weight (IL-22 KO mice vs. wild-type mice; RV/LV+IVS: 0.48±0.05 vs 0.40±0.02, P=0.002). IL-22 KO mice exhibited significant RV enlargement and RV dysfunction 4 weeks after PAB. (RVEDV: 10±2.3mm2 vs 12.9±3.1mm2, P=0.005, FAC: 35.2±7.8% vs 23±6.0%, P&lt;0.001). Four weeks after PAB, the frequency of tricuspid regurgitation (TR) in IL-22 KO mice was significantly higher than that in wild type mice (100% vs 30%, P=0.004).Transcriptome analysis showed that genes related to extracellular matrix (ECM) organization, including collagen formation, which are involved in fibrosis during RV failure, were less upregulated in Il-22 KO mice after PAB, in contrast to the echo results of reduced RV function. Interestingly, genes related to elastic fiber formation, such as Fbn1 and Eln, were particularly less elevated in Il-22 KO mice compared to WT mice after PAB. Conclusions: These results suggest that IL-22 may play a prophylactic role in RV remodeling and tricuspid regurgitation development during pressure overload through a unique mechanism.
Abstract 4140810: Impact of Neutrophil on Ischemic Risk in Acute Coronary Syndrome Patients Across Different Low Density Lipoprotein Cholesterol Levels
Authors: Kailun Yan, Jiawen Li, Kexin Zhang, Menglu Liu, Jinqing Yuan, Xueyan Zhao
Journal: Circulation (2024)

Background: Inflammation is a significant residual risk factor for coronary artery disease. While intensive lipid-lowering therapy has reduced the prevalence of plaque rupture, plaque erosion in acute coronary syndrome (ACS) patients is increasing, with neutrophils playing a crucial role. It remains unclear whether varying low-density lipoprotein cholesterol (LDL-C) levels modify the relationship between neutrophil count and ischemic risk in ACS patients. Aim: To investigate the relationship between neutrophil counts and ischemic risk in ACS patients undergoing percutaneous coronary intervention (PCI) across different LDL-C levels. Methods: This large cohort study enrolled consecutive 10724 patients undergoing PCI at Fuwai Hospital (Peking Union Medical College) throughout the year of 2013. Patients were divided into subgroups according to baseline LDL-C levels, with cut-off points at 1.8mmol/L or 1.4mmol/L. The primary endpoint was major adverse cardiovascular event (MACE), and the secondary endpoint was revascularization. Results: Finally, 5717 ACS patients with PCI were included. The mean age was 58.43 ± 10.35 years, with 4399 (76.9%) being male. During the 5-year follow-up period, 1058 (18.5%) MACEs and 821 (14.4%) revascularizations were recorded. Restricted cubic spline analysis revealed a positive correlation between neutrophil and MACE and revascularizations only in patients with lower LDL-C levels (LDL-C &lt;1.8 and LDL-C &lt;1.4 mmol/L), but not in those with higher LDL-C levels (LDL-C ≥1.8 and LDL-C ≥1.4 mmol/L) (Figure 1) . Multivariate Cox regression analysis showed that in the LDL-C &lt;1.8 mmol/L group, each unit increase in neutrophil count was associated with a 1.129 times higher risk of MACE (HR 1.129; 95% CI 1.046-1.219) and a 1.130 times higher risk of revascularizations (HR 1.130; 95% CI 1.031-1.238). Similar findings were observed in the LDL-C &lt;1.4 mmol/L group, where higher neutrophil was independent risk factors for MACE (HR 1.222; 95% CI 1.063-1.404) and revascularizations (HR 1.274; 95% CI 1.078-1.506). However, in patients with higher LDL-C levels (LDL-C ≥1.8 and LDL-C ≥1.4 mmol/L), neutrophil counts were not associated with outcomes (Table 1) . Conclusions： High neutrophil counts are a significant risk factor for ischemic events in ACS patients with low LDL-C levels, highlighting the potential benefits of targeting neutrophils-related inflammatory pathway in the management of ACS patients with well-controlled LDL-C levels.
Abstract 4140921: Characteristics and Outcomes for Patients with Adult Congenital Heart Disease after Initiation of Dialysis for End-Stage Kidney Disease
Authors: Rhythm Vasudeva, Wan Chi Chan, Michael Vlach, Kunal Patel, Monil Majmundar, Mohammad Alarfaj, Mohinder Reddy Vindhyal, Kamal gupta, John Serfas
Journal: Circulation (2024)

Background: In a growing and aging adult population with congenital heart disease (CHD), the prevalence of renal dysfunction is increasing. There is paucity of information regarding the prevalence, spectrum of and outcomes in adult CHD patients with end-stage kidney disease (ESKD). Aims: To determine baseline characteristics of adult patients with ESKD and CHD, grouped by complexity, and to compare their mortality and morbidity outcomes to non-CHD patients. Methods: We analyzed the United States Renal Data System to identify patients ≥ 18 years of age initiating long-term dialysis between 2006 and 2020. Patients were grouped by complexity of CHD - Simple, Moderate and Complex based on ICD codes. We assessed mortality and hospitalization outcomes at 1 and 3 years by comparing percentages and adjusted hazard ratios using the Fine-Gray sub distribution hazard model. Kaplan-Meier curves were also generated. Results: A total of 1513 patients with CHD were identified. The mean age was 65.8 years with complex CHD being the youngest cohort. About 55% of patients were male and White race was the most prevalent. While patients with CHD had a higher prevalence of heart failure and arrhythmias at baseline, patients with complex CHD had especially unique characteristics. They demonstrated a higher prevalence of liver disease, thromboembolism, and causes of ESKD not related to hypertension or diabetes; a lower prevalence of CAD and CVA/TIA; and a shorter time to first hospitalization. Patients with simple [HR 0.67 95% CI (0.53 – 0.85)] and moderate CHD [HR 0.70 (0.60 – 0.81)] had significantly less mortality at 1 year compared to non-CHD patients, with similar findings at 3 years. Hospitalization rates and admissions for CHF exacerbation at 1 year and 3 years were significantly higher amongst all CHD patients, especially in complex CHD (80.4% vs 61.4% in non-CHD patients at 1 year). Kaplan-Meier curves (see Figure) over a 10-year follow-up showed significantly lesser mortality and increased hospitalizations amongst CHD patients (p &lt;0.0001). Conclusion: Patients with CHD and ESKD have better long-term survival than patients without CHD upon initiating dialysis despite higher rates of hospitalizations and heart failure admissions.