tbuckley/cabot-search huggingface dataset:
Abstract 4136452: Acute Cardiac Function Change After Catheter Ablation of Ventricular Arrhythmias in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Nathaniel Davis, Fatima Ezzeddine, Alan Sugrue, Konstantinos Siontis, Suraj Kapa, Gurukripa Kowlgi, John Giudicessi, John Bois, Ian C Chang, Samuel Asirvatham, Paul Friedman, Ammar Killu
Journal: Circulation (2024)

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder characterized by fibrofatty replacement of myocardial tissue, creating areas of electrical heterogeneity and increasing the risk of ventricular arrhythmias (VAs) and sudden cardiac death (SCD). Catheter ablation is commonly performed in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) for management of ventricular arrhythmias (VAs). Whether catheter ablation affects cardiac function post-procedurally is uncertain. Research Question: Does catheter ablation for ARVC result in acute change in cardiac function? Goals/Aims: To assess the impact of catheter ablation for VAs on cardiac function in the acute post-procedure setting. Methods: This retrospective study included patients with ARVC who underwent catheter ablation for VAs at Mayo Clinic. Cardiac function was assessed on pre- and post-procedure transthoracic echocardiograms (TTEs). Post-procedure TTEs were obtained within 4 weeks after the ablation procedure. Right ventricular (RV) enlargement and systolic dysfunction were evaluated as continuous variables (0=none, 1=mild, 2=mild-moderate, 3=moderate, 4=moderate-severe, 5=severe). Results: The study included 32 patients who underwent a total of 44 ablations. Mean age at the time of ablation was 49±16 years, and 24 (75%) were male. After a mean follow-up duration of 2.6±5.5 days, there was a significant worsening in mean RV dysfunction (1.6±1.5 to 2.0±1.4, P = 0.001). There were no significant changes in mean left ventricular ejection fraction (LVEF), left ventricular (LV) dimensions, and RV size. 6 (14%) patients had a &gt;5% decline in LVEF, and 14 (32%) patients had worsening RV function. Transient inotropic support was required in 4 (9%) patients. Conclusion(s): This study is the first to assess the acute impact of catheter ablation for VAs on cardiac function in ARVC patients. These results underscore the importance of careful post-procedure monitoring and planning of the ablation target in these patients to avoid excessive ablation and therefore impairment in cardiac function.
Abstract 4136565: Atrial Fibrillation Linked to Right Ventricular Dysfunction in Patients with Acute Pulmonary Embolism
Authors: Quinn Mallery, Riya Gupta, Jacob Clarke, Frances Greathouse, Myoung Hyun Choi, Simran Koura, Elizabeth Bruno, Punit Arora, Waddah Malas, Parth Shah, David Sutherland, Amudha Kumar, Igor Wroblewski, Amir Darki
Journal: Circulation (2024)

Background: Atrial fibrillation (AF), both new-onset and preexisting, is linked to increased mortality in acute pulmonary embolism (APE). The causal pathway for this association, whether through increased right ventricular dysfunction (RVD) is less well understood. Hypothesis: AF independently predicts RVD in APE patients, affecting mortality and clinical outcomes. Goals: Examine the relationship between AF and RVD to understand its impact on APE survival. Guide further research into optimal APE therapeutic strategies, focusing on early rhythm control. Methods: We conducted a retrospective, multi-center cohort study using data from our Pulmonary Embolism Response Team (PERT) registry. Inclusion criteria included PERT activation and adults over 18. Exclusions were for missing transthoracic echocardiogram (TTE) within 3 days or incomplete TTE data. Patients were categorized by AF status, with RVD assessed by TTE markers. Analysis involved logistic regression and Cox proportional hazards models. Results: Among 535 APE patients, 15% had AF. These patients showed higher unadjusted RVD rates (56% vs. 39%, p=0.006) and significant differences in TTE parameters: TAPSE (1.72 vs. 1.89 cm, p=0.007), S` (11.5 vs. 13.4 cm/s, p=0.0002), and RVOT VTI (13 vs. 14 cm, p=0.019). Adjusted analyses confirmed AF's significant association with RVD (OR 2.32, CI 1.3-4.1), inpatient mortality (OR 4.9, CI 1.5-17, p=0.0106), acute renal failure (OR 2.2, CI 1.2-4.1, p=0.0102), and one-year mortality (HR 1.9, CI 1.06-3.44, p=0.03). Conclusions: AF significantly influences mortality in APE, partly through increased RVD. These findings underline the need for further studies to confirm these relationships and enhance treatment strategies.
Abstract 4136459: Machine Learning in Time-to-Event Prediction of Ventricular Arrhythmias among Older Adults with Type 2 Diabetes and Coronary Artery Disease
Authors: Yein Jeon, Thomas Payne
Journal: Circulation (2024)

Introduction: Patients with Type 2 diabetes mellitus (T2DM) have an increased risk for coronary artery disease (CAD) compared to patients without T2DM. Ventricular arrhythmias (VA), such as ventricular fibrillation and ventricular tachycardia, are the major causes of mortality among patients with CAD. Thus, T2DM patients with CAD, especially older adults, have a higher risk of VA compared to patients without T2DM. The time-to-event prediction can contribute to decreasing mortality due to VA in older adults with T2DM and CAD by providing an estimated time and probability of diagnosis at specific time points. However, the limited number of older T2DM patients with CAD, who are diagnosed with ventricular arrhythmias, lowers the performance of a traditional time-to-event analysis model. Hypothesis: We hypothesize that machine learning can improve performance in time-to-event prediction. Methods: This study includes 3975 participants aged &gt;65 years, diagnosed with T2DM and CAD in the All of US database. The baseline time was the earliest date when the patients were older than 65 years and diagnosed with T2DM and CAD. Of all participants, 379 were diagnosed with VA within 5 years from baseline. We compared the machine learning–based time-to-event analysis models to the Cox Proportional Hazards model to explore the potential of machine learning in time-to-event analysis. Additionally, the Synthetic Minority Oversampling Technique was applied to resolve the imbalanced data issue. The model performance was evaluated based on the concordance index, which calculates the correlation between predicted risk scores and actual observations, after 5-fold cross-validation. Results: The average concordance index of the Gradient Boosting Machines model was the highest among the five models, including the Cox Proportional Hazards model, with balanced data (Table). Conclusion: We identified that machine learning could improve the performance of prediction models in time-to-event analysis. The Synthetic Minority Oversampling Technique could mitigate the issue of imbalanced data. In addition, machine learning-based survival models showed higher concordance index values compared to the Cox Proportional Hazards model.
Abstract 4136554: Comparison of short- and long-term atherosclerotic cardiovascular disease risk assessment tools in US young adults
Authors: Yiyi Zhang, Mengying Xia, Kristi Reynolds, Hui Zhou, Mengnan Zhou, Norrina Allen, Abigail Gauen, Lucia Petito, Vanessa Xanthakis, Monika Safford, Lisandro Colantonio, Jamal Rana, Brandon Bellows, Andrew Moran, Jaejin An
Journal: Circulation (2024)

Background: In 2023, the AHA published the PREVENT equations for estimating atherosclerotic cardiovascular disease (ASCVD) risk in adults aged 30-79 years. Research Questions: In young adults aged 20-39 years, does PREVENT improve risk prediction for 10- and 30-year ASCVD compared with existing risk assessment tools recommended in the current US guidelines (i.e., Pooled Cohort Equations [PCEs] and Pencina et al. equations)? Aims: To compare the performance of PREVENT vs. PCEs in predicting 10-year ASCVD, and PREVENT vs. Pencina equations in predicting 30-year ASCVD in young adults. Methods: We analyzed data from two complementary sources: (1) pooled data from two large cohorts: Coronary Artery Risk Development in Young Adults (CARDIA) and Framingham Heart Study (FHS; including the Offspring, Third Generation, Omni 1, and Omni 2 cohorts), and (2) electronic health records from Kaiser Permanente Southern California (KPSC). We included adults aged 20-39 years without a history of ASCVD at baseline. The outcome was incident ASCVD (defined as myocardial infarction, fatal coronary heart disease, fatal and nonfatal stroke) at 10 or 30 years. Model discrimination (Harrell’s C) and mean calibration (estimated as the ratio of predicted to observed event rates) were calculated for the overall population and stratified by sex and race/ethnicity. Results: We included 7,606 young adults (mean age 29 years, 53% female, 30% Black) from the pooled cohorts, and 284,667 (mean age 32 years, 61% female, 8% Black, 46% Hispanic) from KPSC. When predicting 10-year risk, PREVENT improved discrimination in both the pooled cohort (ΔHarrell’s C=0.052; 95% CI: 0.014, 0.095) and KPSC (ΔHarrell’s C=0.039; 95% CI: 0.028, 0.049) compared with the PCEs. PREVENT had good calibration (mean calibration ranged from 0.77 to 1.54), whereas the PCEs overestimated 10-year risk (mean calibration ranged from 1.99 to 4.82). When predicting 30-year risk, discrimination was similar for PREVENT and Pencina equations, but both algorithms underestimated 30-year risk with PREVENT showing worse calibration (mean calibration 0.61). Conclusion: PREVENT improved 10-year ASCVD risk prediction in young adults compared to the PCEs but underestimated 30-year risk.
Abstract 4136604: Efficacy of angiotensin receptor blockers in thoracic aortic aneurysm: meta-analysis of randomized controlled trials
Authors: Lokman Hekim Tanriverdi, Muhammed Melih Dogan, Annie Barrett, Mohammad Zafar, Bulat Ziganshin, John Elefteriades
Journal: Circulation (2024)

Background: Thoracic aortic aneurysm (TAA) poses a significant risk of aortic dissection and mortality. Angiotensin receptor blockers (ARBs) have been proposed as a potential therapeutic intervention to mitigate these risks but their effects are uncertain. Aim: To evaluate the efficacy of ARBs in patients with TAA. Methods: A comprehensive search of Cochrane CENTRAL, Ovid Medline R, Pubmed, and Web of Science yielded 2563 records, from which 8 unique randomized controlled trials (RCTs) (including 7 Marfan and 1 bicuspid aortic valve+TAA populations) comprising 1575 patients were included in the analysis. The primary outcome measures were aortic dissection and all-cause mortality. Pooled risk ratios (RR) or mean differences (MD) in an inverse variance random-effects model were generated and analyses were performed with “meta” package in R (version 4.3.2). Results: Our analysis reveals no significant beneficial effect of ARBs on aortic dissection (RR 0,62 [95%CI, 0,20; 1,92], I 2 :0%) and all-cause mortality (RR 0,61 [95%CI, 0,18; 2,05], I 2 :0%), irrespective of specific ARB agents (including losartan, irbesartan, and telmisartan), comparators (beta blocker, placebo, or no treatment), disease condition (Marfan syndrome or bicuspid aortic valve), and patient demographics (children or adults). Additionally, there were no significant differences observed between ARB and control groups in changes in ascending aorta and aortic annulus diameter, as well as aortic Z-score at the 3-year mark, including the annual change in ascending aorta (MD 0.04 mm/year [95% CI, -0.07 to 0.15], I 2 :0%) and aortic root diameter (MD -0.06 mm/year [95% CI, -0.22 to 0.10], I 2 :81%) by echocardiography. However, there was a significant reduction in aortic root diameter as assessed by MRI (MD -0.48 mm/year [95%CI, -0.89 to -0.08]) and echocardiography (MD -0.51 mm/3year [95%CI, -0.85 to -0.17]), with low heterogeneity when compared with control. Risk of aortic surgery and severe adverse events were also comparable. Conclusion: We found no significant beneficial effect of ARBs in reducing the risk of aortic dissection or all-cause mortality in patients with TAA. Despite observing a significant reduction in the aortic root diameter by MRI and echocardiography with ARB therapy, other imaging outcomes were comparable between ARB and control groups.
Abstract 4136463: Novel Systemic Inflammatory Biomarkers Can Predict Significant Coronary Disease in High Risk Patients
Authors: Dania Bani Hani, Jafar Alshraideh, Hamzah Alduraidi, Salah Al-Zaiti
Journal: Circulation (2024)

Background: Coronary artery disease (CAD) is a major cause of morbidity and mortality worldwide. Chronic inflammation is a known risk factor for atherosclerosis, plaque formation, disease progression, and plaque instability. Novel inflammatory biomarkers have been recently linked to excess risk of adverse cardiovascular events, including incident myocardial infarction. Elevated inflammatory biomarkers may help identify patients at higher risk for severe CAD. Aim: This study aimed to evaluate the use of novel systemic inflammatory markers in predicting the pretest probability of severe CAD in patients referred to diagnostic coronary angiography in a single tertiary care center. Methods: This was a prospective observational cohort study enrolling consecutive patients referred to diagnostic coronary angiography in a tertiary care center. Preprocedural laboratory results were obtained from medical charts, including complete blood counts with differentials. Three novel systemic inflammatory markers were computed using existing mathematical formulas: systemic immune-inflammation index (SII = neutrophil count*platelet/lymphocyte); systemic inflammation response index (SIRI = neutrophil*monocyte/lymphocyte); and systemic immune inflammatory response index (SIIRI = neutrophil*monocyte*platelet/lymphocyte). The primary study outcome was severe CAD defined as the presence of ≥70% stenosis in one of three main coronary arteries requiring percutaneous coronary intervention). The outcome was adjudicated by an independent reviewers blinded to computations of biomarkers. Result: The sample included 264 patients (age 59.3±10.8, 47% Females). Overall, 84 patients (32%) met the primary study outcomes. In univariate analysis, those with severe CAD had significantly higher SIRI (2.9±0.7 vs. 2.6±0.6, p = 0.001) and SIIRI (8.4±0.8 vs. 8.1±0.7, p = 0.015) compared to their counterparts. In multivariate analysis adjusted for age and sex, only SIRI was an independent predictor of severe CAD. Using SIRI &gt; 20.8 (upper quartile) was associated with nearly three-fold excess risk of severe CAD (OR = 2.72, 95% CI 1.45-5.09). Conclusion: Elevated SIRI, a marker of ongoing systemic inflammatory response, could be indicative of severe CAD. As an inexpensive biomarker based exclusively on complete blood count, SIRI can be used to prioritize patients referred for diagnostic angiography and potentially expedite treatments in those at higher risk for coronary events.
Abstract 4136687: VTRNA2-1 Promoter Methylation as a Prognostic Biomarker in Peripheral Artery Disease: Implications for Maternal Nutritional Influence
Authors: Ming-lung Tsai, Yi-Chun Huang, Chao-Yung Wang
Journal: Circulation (2024)

Background: Peripheral artery disease (PAD) is associated with high morbidity and mortality and is closely related to diabetes mellitus (DM) and atherosclerosis. Recent advances in epigenetics have highlighted the critical relationships of non-coding RNA Vault RNA 2-1 (VTRNA2-1) promoter methylation and periconceptional nutritional status. Furthermore, the abundance of methylation of the VTRNA2-1 promoter is associated with glucose metabolism and cell aging. This study investigates the association between VTRNA2-1 promoter methylation and clinical outcomes in PAD patients requiring revascularization. Hypothesis: VTRNA2-1 promoter methylation status is associated with clinical outcomes in PAD patients requiring revascularization. Methods: A total of 133 PAD patients requiring revascularization were enrolled. Inclusion criteria included adults over 20 years old, consent to participate, and a requirement for angioplasty. Blood samples were processed to isolate leukocytes, and DNA was extracted using the DNeasy blood kit. Bisulfite pyrosequencing was performed to quantify CpG site-specific DNA methylation at the VTRNA2-1 promoter locus. General population samples from the National Health Research Institutes were used as the control group to compare the methylation status. Patients' one-year clinical outcomes were evaluated. Results: The study found significant differences in VTRNA2-1 promoter methylation status between PAD patients and the control group (P &lt; 0.001). Hypomethylation of VTRNA2-1 promoter was associated with a higher amputation rate in PAD patients (HR 2.19, 95% CI 1.09-4.42, p=0.027). Among patients without ESRD (N=79), those with hypomethylation had a significantly increased risk of major adverse limb events (MALE) (HR 2.78, 95% CI 1.11-6.97, p=0.024), amputations (HR 2.58, 95% CI 1.02-6.57, p=0.044), and progression to ESRD (p=0.039). Conclusion: The methylation status of VTRNA2-1 promoter is significantly different between PAD patients and the normal population, with hypomethylation linked to poorer clinical outcomes in PAD patients undergoing revascularization. These findings suggest that VTRNA2-1 promoter methylation status could serve as a valuable biomarker for predicting prognosis and guiding treatment strategies in PAD. Our results open a molecular link between the periconceptional environment and the risks of PAD.
Abstract 4136511: Targeting ATP Citrate Lyase: A Novel Therapeutic Strategy for Vascular Remodeling in Pulmonary Hypertension
Authors: Yann Grobs, Charlotte Romanet, Sarah-Eve Lemay, Alice Bourgeois, Pierre Voisine, Charlie Theberge, Melanie Sauvaget, Sandra Breuils Bonnet, Sandra Martineau, EL-Kabbout Reem, Andreanne Pelletier, Manon Mougin, Elizabeth Dumais, Jean Perron, Nicolas Flamand, Francois Potus, Steeve Provencher, Olivier Boucherat, Sebastien Bonnet
Journal: Circulation (2024)

Introduction: Pulmonary arterial hypertension (PAH) is a vascular remodeling disease characterized by a progressive obliteration of distal pulmonary arteries (PA), which is driven by a cancer-like pro-proliferative phenotype of smooth muscle cells (SMCs). A metabolic shift towards glycolysis and changes in the epigenetic landscape contribute to this abnormal phenotype. ATP Citrate Lyase (ACLY) is an enzyme that plays a role in promoting the Warburg effect, lipid synthesis, and chromatin remodeling in cancer. However, its role in PAH remains unknown. We hypothesized that ACLY is upregulated in PAH and supports the abnormal phenotype of PAH-PASMCs . Methods/Results: To investigate this hypothesis, we measured ACLY expression in human distal pulmonary arteries and isolated PASMCs from PAH patients (immunoblot/Immunofluorescence). We found increased expression and activation of ACLY in PAH-PASMCs, with preferential localization in the nucleus. Inhibition of ACLY using BMS-303141 or siACLY decreased PAH-PASMCs proliferation (Ki67/MCM2, PLK1, PCNA) and survival (Annexin V/SURVIVIN). ACLY inhibition also reduced glycolysis markers and increased mitochondrial respiration. Additionally, the inhibition of ACLY lowered cholesterol levels and lipid droplet accumulation in PAH-PASMCs. Further analysis showed that ACLY promotes nuclear acetyl-CoA production, leading to acetylation of specific histone proteins and GCN5-mediated transcriptional activation of genes involved in cell cycle progression. The transcription factor FOXM1 appeared to mediate this genetic signature. In vivo , pharmacological inhibition of ACLY using BMS-303141 significantly improved pulmonary vascular remodeling (Elastica Van Gieson staining, EVG) and right ventricular function (RVSP, mPAP, TAPSE, S-Wave, SV by echocardiography and right heart catheterization) in Su/Hx-challenged rats with established PAH. SMC-specific Acly K.O mice were protected against Su/Hx-induced PAH. Consistently, tamoxifen-induced SMC-specific Acly deletion improved hemodynamics parameters in Su/Hx mice. These therapeutic effects were associated with a reduced acetylation of H3K27 and H3K9 (IF). Ex vivo , inhibition of ACLY attenuated vascular remodeling (EVG) in human precision cut lung slices exposed to a growth factor cocktail. Conclusion: Our study reveals that ACLY plays a critical role in vascular remodeling in PAH and its pharmacological inhibition may represent a novel and attractive avenue as therapeutic treatment.
Abstract 4136539: Management of Malignant SVC Syndrome and Acute SVC Thrombosis with Complex Endovascular Intervention
Authors: Karley Fischer, Ananya Reddy, Damian Valencia, Abdur Rehman
Journal: Circulation (2024)

Superior vena cava (SVC) syndrome occurs when there is SVC occlusion or obstruction. SVC obstruction can cause an increase in venous return pressure up to 40 mm Hg, producing edema of the face, neck and chest wall. Blood flow can be diverted to the right atrium through collateral venous networks in cases of gradual SVC compression. The most common cause of SVC syndrome is malignancy, as seen in 70% of cases. Traditionally, treatment is with radiation therapy but advances have now allowed for an endovascular approach. We present a case of malignant SVC syndrome with a complex percutaneous treatment approach that provided palliation with near immediate symptom improvement. A 64 year-old-female with history of cerebrovascular accident on Eliquis, right upper lobe squamous cell carcinoma of the lung in remission, and a mediastinal nodule under surveillance presented with facial and bilateral upper extremity edema. CT revealed bilateral pulmonary embolism and a large SVC thrombus causing impaired venous return. Invasive angiogram confirmed a 95% thrombotic tubular stenosis for which she underwent aspiration thrombectomy with alpha VAC F-18, then angioplasty with an Armada (Abbott) 10 x 40 mm compliant balloon and stenting with the Express (Boston Scientific) 10 x 37 mm stent. There was 0% residual stenosis and immediate clinical improvement. Oncological workup confirmed the right mediastinal mass to be a recurrence of squamous cell carcinoma. SVC syndrome occurred due to mediastinal mass compression and a near occlusive SVC thrombus. Aspiration thrombectomy was effective in treating the SVC thrombosis and was performed alongside pulmonary embolism thrombectomy. The Armada balloon is intended for lesion dilation in the peripheral arteries, but was safely used here for venous dilation. The Express stent is intended for palliation of malignant biliary neoplasms but has versatility and was utilized here for malignant neoplasm surrounding the SVC. Peripheral endovascular stenting is an advantageous treatment option for malignant SVC syndrome given the challenges due to recurrence from mass effect. This provides additional support to maintain vessel patency and is a safe palliation option for improvement in quality of life.