tbuckley/cabot-search huggingface dataset:
Abstract 18221: Interleukin-6 in Patients With HFrEF and the Effect of Dapagliflozin: Insights From DAPA-HF
Authors: Kieran Docherty, Paul Welsh, Inder S Anand, David Berg, Rudolf A de Boer, Lars Kober, Mikhail N Kosiborod, Felipe Martinez, Eileen OMeara, David Morrow, Mark Petrie, Piotr Ponikowski, Marc S Sabatine, Morten Schou, Naveed Sattar, Ann Hammarstedt, Anna Maria Langkilde, Mikaela Sjostrand, Scott Solomon, Pardeep S Jhund, John J McMurray
Journal: Circulation (2023)

Introduction: Inflammation plays an important pathophysiological role in the development and progression of heart failure (HF). Interleukin-6 (IL-6) is a circulating cytokine which is the main regulator of the release of C-reactive protein (CRP) along with pro-inflammatory cytokines. It has been suggested that one of the potential mechanisms of action of sodium glucose co-transporter 2 (SGLT2) inhibitors may be to reduce inflammation. We examined the association between IL-6 and outcomes in patients with HF with reduced ejection fraction (HFrEF) in the DAPA-HF trial and its relationship with the effect of dapagliflozin. Methods: Key inclusion criteria were: 1) NYHA class II-IV, 2) LVEF ≤40%, 3) elevated NT-proBNP and 4) eGFR ≥30 ml/min/1.73m 2 . The primary outcome was a composite of a first episode of worsening HF or cardiovascular death. IL-6 (Roche Diagnostics, e411) was measured at baseline and 52 weeks. Results: Median (IQR) baseline IL-6 was 6.01 pg/mL (interquartile range 4.18-9.29) in the 2980/4774 with available data. Baseline IL-6 quartiles were: Q1 ≤4.18 pg/mL, Q2 4.19-6.01 pg/mL, Q3 16.02-9.29 pg/mL, Q4 ≥9.3 pg/mL. Median high-sensitivity CRP at baseline was 1.13 mg/L and 3.78 mg/L in those with an IL-6 level &lt; or ≥ the median, respectively. The adjusted risk of the primary outcome relative to Q1 was: Q2 = HR 1.39 (95%CI 1.02, 1.89), Q3 = HR 1.55 (1.15, 2.08), Q4 = 2.07 (1.55, 2.76) ( Fig A ). The beneficial effect of dapagliflozin compared with placebo was consistent whether IL-6 was analysed in quartiles (P int = 0.77) or as a continuous variable (P int = 0.69 [ Fig B ]). The placebo-corrected relative change in IL-6 at 52 weeks was -4.1% (95%CI -9.1, +1.2), p=0.13. Conclusions: In DAPA-HF, elevated IL-6 levels were an independent predictor of the risk of cardiovascular death or worsening HF. Dapagliflozin reduced the risk of cardiovascular death or worsening HF regardless of baseline IL-6.
Abstract 14909: Door-to-Diuretic Time and Mortality in Patients With Acute Heart Failure: A Meta-Analysis
Authors: Thalys Sampaio Rodrigues, Levindo Jose Garcia Quarto, Savio Nogueira, James D Theuerle, Omar Farouque, Louise M Burrell, Anoop N Koshy
Journal: Circulation (2023)

Background: Recent studies have highlighted potential benefit with time-to-therapy of intravenous (IV) diuretics in patients with acute heart failure (AHF), although the data is conflicting. We sought to evaluate the impact of door-to-IV diuretic time on mortality in patients with AHF presenting to hospital. Methods: Electronic databases were searched for prospectively registered (PROSPERO CRD42023394255) studies published up to February 2023 that evaluated the effect of door-to-IV diuretic time on clinical outcomes in AHF. The primary outcome was in-hospital mortality and the secondary outcome 30-day all-cause mortality. Three reviewers independently appraised the data, with summary odds ratios (OR) and 95% confidence intervals (CIs) pooled using a random-effects model. Results: Seven observational studies comprising 29,102 patients were included. Three studies were prospective in design. Diuretics of choice were furosemide or bumetanide. Early IV diuretic administration was defined as a reference range from 30 to 105 minutes. Early IV diuresis was not associated with any difference in in-hospital mortality (OR 0.84, 95% CI 0.57-1.24) with high heterogeneity (I 2 =74%). However, pooled data from 4 studies evaluating 30-day outcomes demonstrated reduced 30-day mortality (OR 0.77, 95% CI 0.64-0.93). Conclusion: Door-to-IV diuretic time was not associated with reduced in-hospital death but was associated with significantly improved 30-day mortality. Prospective trials are warranted to evaluate the effect of early IV diuresis across heart failure phenotypes and disease severities.
Abstract 15932: <i>Lactobacillus</i> Suppresses Glycoprotein-130-Mediated Microtubule Remodeling to Support Right Ventricular Function in Pulmonary Arterial Hypertension
Authors: Sasha Z Prisco, Madelyn Blake, Neal Vogel, Felipe Kazmirczak, Edward K Weir, Thenappan Thenappan, Kurt W Prins
Journal: Circulation (2023)

Introduction: Microtubules (MTs) are crucial for cardiomyocyte function as they regulate t-tubule structure, nuclear morphology, and gap junction protein localization. Glycoprotein-130 (GP130) signaling promotes pathological MT remodeling and right ventricular (RV) dysfunction in pulmonary arterial hypertension (PAH), but the trigger for the inflammation-MT connection is unknown. Microbiome dysbiosis activates systemic inflammation, and levels of the anti-inflammatory bacteria Lactobacillus are associated with RV function in rodents. However, the direct effects of Lactobacillus on GP130 signaling, MT remodeling, and RV function in PAH are unknown. Methods: Rats were randomly allocated into 3 groups: control, MCT-water, and MCT rats given Lactobacillus (MCT- Lactobacillus ). Echocardiography and pressure-volume loops defined RV function. Next-generation sequencing evaluated the composition of the bacterial components of the fecal microbiome. SomaScan proteomics quantified the serum proteome. RV and jejunal morphology were assessed with light and super resolution confocal microscopy. The relationship between Lactobacillus abundance and RV response to afterload was assessed in 65 PAH patients. Results: Lactobacillus augmented RV function (A) and reduced RV hypertrophy and fibrosis without altering PAH severity. Lactobacillus shifted the serum proteomic signature towards control (B) and reduced circulating GP130 ligands, normalized RV t-tubule architecture (C), MT density (D), and nucleus size (E), and prevented connexin-43 lateralization in RV cardiomyocytes (F). Lactobacillus restructured the microbiome, and concomitantly improved jejunal epithelial cell morphology with increased villus/microvillus length and glycocalyx thickness. PAH patients with fecal Lactobacillus had superior RV adaptation as afterload increased (G). Conclusion: Lactobacillus combats GP130-mediated MT remodeling to support RV function.
Abstract 15490: NIL10: A Novel Nanotechnological Compound to Prevent Monocyte Infiltration and Adverse Cardiac Remodeling in a Porcine Model of Myocardial Ischaemia-Reperfusion
Authors: Laura Tesoro, Beatriz Jimenez, Rafael Ramirez-Carracedo, Laura Botana, Ignacio Hernandez Navarro, Javier Diez Mata, Nunzio Alcharani, Claudia Gonzalez-Cucharero, Marta Saura, Jose Zamorano, Carlos Zaragoza
Journal: Circulation (2023)

Introduction: Adverse cardiac remodeling following acute myocardial infarction (AMI) depends on how promptly the phagocytic-nuclear system responds. Among strategies to limit the inflammatory response, we have developed a nanoparticle (NIL10) which binds to IL-10 receptor (IL-10R) in-vitro and promotes macrophage polarization towards a resolutive phenotype in animal models of myocardial ischemia-reperfusion (I/R). However, its therapeutic use still depends on understanding its ability to regulate monocyte recruitment. Hypothesis: Targeting the IL-10R in circulating monocytes may represent a new therapeutic approach to improve cardiac function in patients undergoing AMI. Objective: To explore the molecular mechanisms leading to the inhibition of monocyte recruitment by NIL10 in pigs undergoing cardiac I/R. Methods: By using a porcine model of myocardial I/R, we arranged the following groups: (1) control group (2) intravenous administration (IV) 1 mg/kg NIL10, (3) IV of 4x10 5 isolated monocytes from group 2, (4) IV of 4x10 5 isolated monocytes from group 1 and then incubated with NIL10 (A). Results: Groups 2-4 exhibited better cardiac function compared to group 1 (B), which resulted in a decrease in myocardial fibrosis (C), along with a reduction of circulating CCR2+ monocytes (D) and a decrease in classical-monocyte infiltration, as shown by a reduction of CCR2+ macrophages in the necrotic area of the heart (E). As a result, CCL2 plasma expression, a functional ligand of CCR2, was decreased by day 7 post-I/R (F) in contrast to the necrotic tissue expression profile in which we detected large amounts of CCL2 (G) and STAT3 activation, indicative of IL10R activity (H). Conclusion: In addition to macrophage polarization, NIL10 induces cardiac protection by limiting classical monocyte infiltration after myocardial I/R, which opens a new window for using, in combination with endogenous monocyte therapy, to treat AMI.
Abstract 17494: The Incremental Risk Prediction of Cardiac CTA-Derived Quantitative Atherosclerosis in the International Advance Registry
Authors: Kavitha M Chinnaiyan, Ilana Guez, Vida Sussman, Manesh R Patel, Bjarne L Norgaard, Timothy Fairbairn, Nieman Koen, lynne koweek, Gianluca Pontone, Neils P Sand, Jeroen Sonck, Mark Rabbat, Sarah Mullen, Nicholas Ng, Bernard De Bruyne, Campbell Rogers, Hitoshi Matsuo, Jeroen J Bax, Jonathon Leipsic
Journal: Circulation (2023)

Background: We sought to assess the incremental prognostic utility of AI-enabled quantitative coronary plaque assessment (AI-QCPA) beyond stenosis severity and FFR CT , for the prediction of late revascularization and MACE in the large prospective international ADVANCE registry. Methods: 4737 participants were submitted for AI-QCPA evaluation. Total plaque volume (TPV), calcified plaque volume (CPV), non-calcified plaque volume (NCPV), and low attenuated plaque volume (LAPV) were quantified. In addition, total percent plaque volume (TPAV) and its components were calculated (PV/Vessel Volume * 100). Demographics, stenosis severity, lowest FFR CT , and Delta FFR CT were also recorded. To explore the relationship between plaque measures and MACE (death, myocardial infarction, and unplanned hospitalization leading to revascularization) and late revascularization (&gt;90 days) we performed Kaplan Meier event free outcomes analyses following adjustments for stenosis severity, FFR CT and Delta FFR CT . Results: AI-QCPA was available in 4430 subjects. Mean (SD) TPV was 542.4 ± 522.5 mm 3 . Optimal cutpoints of plaque metrics were predictive of MACE and/or late revascularization when adjusted-TPV (HR- 1.45 CI- 1.06-1.98; P=0.02); CPV (HR- 1.65 CI- 1.21- 2.26; p=0.002); NCPV (HR 1.43 CI- 1.02-1.99; P=0.04) and LAPV (HR- 2.23 CI 1.62-3.07; P=0.03 . Stronger risk prediction was achieved by plaque measures adjusted for vessel volume: TPAV (HR 1.92 CI 1.40- 2.64 P&lt;0.001). This incremental risk discrimination of quantitative plaque measures remained significant as a predictor of MACE alone- TPV- (HR 1.84 CI 1.02- 3.29 P=0.04) TPAV (HR 3.33 CI- 1.85- 6.02 P&lt;0.0001) (Figure 1). Conclusions: In this large prospective international registry, AI-QCPA provided incremental risk discrimination for MACE and late revascularization beyond stenosis severity and FFR CT .
Abstract 17441: Non-Invasive Quantification of Peripheral Angioplasty-Induced Vascular Inflammation in a Porcine Model Using PET/CT Imaging
Authors: Mahboubeh Nabavinia, Eleanor T Rimmerman, Corrin Mansfield, Ting-Heng Chou, Michael R Go, Mitchel R Stacy
Journal: Circulation (2023)

Background: Similarities in peripheral vascular anatomy between swine and humans make this animal an ideal model for evaluating the effects of lower extremity angioplasty procedures commonly performed to improve limb blood flow in peripheral artery disease (PAD). Hypothesis: We hypothesized that PET/CT imaging would provide a non-invasive strategy for quantifying the inflammatory response to balloon overdilation injury in a swine model of peripheral angioplasty. Methods: Five Yorkshire pigs (weight = 25 kg) underwent overdilation of the right femoral artery. A balloon catheter (7 mm x 40 mm) was introduced via the carotid artery and guided to the femoral artery under fluoroscopy. The balloon was then inflated to a pressure 1.5 times greater the recommended nominal pressure to induce arterial injury. 18 F-fluorodeoxyglucose (FDG) PET/CT imaging was performed 14 days after angioplasty to quantify in vivo inflammation in the injured and control femoral arteries, which was expressed as the maximum standardized uptake value (SUV max ). Pigs were euthanized 14 days post-angioplasty and arteries were harvested and sectioned for gamma counting ( 18 F-FDG uptake), and stained with hematoxylin and eosin histology (H&amp;E), Masson’s trichrome, and alpha-smooth muscle actin (α-SMA) for evaluation of intimal remodeling and smooth muscle cell proliferation. Results: 18 F-FDG PET/CT imaging quantified a significant increase in inflammation for the injured versus control femoral artery 14 days post-angioplasty (p=0.04). Gamma counting confirmed a significant increase in 18 F-FDG uptake in the injured artery (p=0.02). H&amp;E revealed a significant increase in intimal thickening in the injured artery (p=0.03). α-SMA expression was also significantly increased in the injured versus control femoral artery (p=0.01), demonstrating an increase in smooth muscle cell proliferation. Conclusions: 18 F-FDG PET/CT quantifies arterial inflammation resulting from overdilation injury that is associated with intimal remodeling and smooth muscle cell proliferation. PET/CT imaging may provide a non-invasive strategy for in vivo testing of the efficacy of emerging drug-coated endovascular peripheral devices.
Abstract 13688: Association Between Daylight Saving Time and Acute Myocardial Infarction in Canada
Authors: Ahmad Al Samarraie, Roger Godbout, Remi Goupil, Catalin Paul Suarasan, Melina Russo, Samaya Kanj, Mathilde Dano, Justine Roy, Laurence Reiher, Guy Rousseau, Maxime Pichette
Journal: Circulation (2023)

Background: Recent studies have suggested an increased risk of AMI following daylight saving time (DST) transitions in cohorts of American and European patients. We aim to validate this finding in a Canadian population. Methods: We performed a retrospective cohort study of patients admitted to the Hôpital du Sacré-Coeur de Montréal, with a diagnosis of AMI requiring a PCI. Patients aged ≥18 years hospitalized between 2018 and 2022 were included. The primary endpoint was the incidence of AMI two weeks following DST transitions. The secondary endpoint was infarct size by biomarker assessment and LVEF. Results: 1142 charts were reviewed with 775 patients meeting the inclusion criteria (244 in the study group and 531 in the control group). Baseline clinical characteristics were comparable between both groups. (Table 1) The rate of AMI per day following DST transitions was 1.74 compared to 1.90 during control periods. DST was not associated with an increase in AMI (IRR = 0.92, 95% CI 0.79 - 1.07, p = 0.295). (Table 2) During the spring shift, the IRR was 0.83, p = 0.106, and during the autumn shift, the IRR was 1.01, p = 0.933. The rate of AMI was higher on the first day following DST, but it did not reach statistical significance (rate of AMI per day = 2.00; IRR = 1.05; p = 0.845). The transition to DST was not associated with a larger infarct size by CK-MB assessment, but LVEF was significantly slightly higher following DST transitions (LVEF 50 ± 11 % vs 48 ± 10 %, p = 0.038). Conclusion: In this cohort of Canadian patients, there was no significant association between DST transitions and the incidence of AMI. LVEF was higher following DST transitions, but infarct size was similar between study and control groups.
Abstract 14035: Clinical Outcomes Following Hospitalization for COVID-19 in Patients With Cardiac Sarcoidosis in the United States
Authors: Muzammil Farhan, Kamleshun Ramphul, Raheel Ahmed, Azeem Hassan, Ali Hasan, Hasan Ahmad, Joseph Okafor, Caleb Carver, Ayesha Jadoon, Khadija Amanullah, Yumna Jamil, Maham Bilal, Sajeel Ahmed, Rahat A Memon, Hemamalini Sakthivel
Journal: Circulation (2023)

Background: Chronic immunosuppressive therapy and concomitant pulmonary involvement are two possible factors that could contribute towards adverse outcomes for patients with a history of Cardiac Sarcoidosis (CS) who are hospitalised with Covid-19. In this study, we aimed to identify co-morbidities and clinical outcomes for patients with CS post hospitalization for Covid-19. Methods: Patients aged ≥18 years, with a positive diagnosis of COVID-19 (via ICD-10 code “U071”) between 1st April 2020 to 31st December 2020, were identified from National Inpatient Sample Database. Patients with CS were compared for patient characteristics, demographics and hospital-related outcomes against patients without CS using multivariable regression analysis. Results: We identified a total of 1,608,285 cases of COVID-19 infection admitted to the hospital out of whom 60 patients were confirmed to have CS. CS patients were younger (mean 57.8 vs. 63.3 years, p&lt;0.01), had a higher mean Charlson comorbidity index (CCI: 5.17 vs. 2.72, p&lt;0.01) with greater prevalence of previous myocardial infarction (25.0% vs. 4.2%, p&lt;0.01), atrial fibrillation (58.3% vs. 15.6%, p&lt;0.01), smoking (50% vs. 26.1%, p&lt;0.01), chronic kidney disease (66.7% vs. 20.6%, p&lt;0.01) and diabetes (75.0% vs. 40.0%, p&lt;0.01) as compared to patients without CS. Moreover, clinical outcomes of patients with CS were more adverse following hospitalization for COVID-19 including use of mechanical ventilation (25.0% vs. 11.2%, p&lt;0.01, adjusted OR 1.39 95% CI: 1.37-1.41), acute kidney injury (50.0% vs. 28.2%, p&lt;0.01, adjusted OR 1.86, 95% CI: 1.84-1.88) and death (25.0% vs. 13.1%, p&lt;0.01, adjusted OR 3.15, 95% CI: 3.10- 3.20) (Table 1). Conclusion: CS patients hospitalized for COVID- 19 infection had greater CCI and worse clinical outcomes such as mechanical ventilation use, acute kidney injury and death when compared to patients without cardiac sarcoidosis. Keywords: Cardiac sarcoidosis, COVID- 19, outcomes.
Abstract 16309: Impact of the Pandemic on AMI Hospitalizations and Outcomes: A Comprehensive Medicare Fee-for-Service Analysis
Authors: Mitsuaki Sawano, Xin Xin, Yuan Lu, Cesar Caraballo, Rohan Khera, Karthik Murugiah, Zhenqiu Lin, Harlan M Krumholz
Journal: Circulation (2023)

Introduction: Studies suggest hospitalizations for acute myocardial infarction (AMI) declined early in the COVID-19 pandemic, but national patterns during the entire pandemic are not well characterized. This study aims to characterize the changes in AMI hospitalizations and 30-day mortality rates among Medicare Fee-For-Service (FFS) beneficiaries during the pandemic. Methods: We used Medicare FFS Part A data from March 2014 to November 2021 consisting of people aged ≥65 years. The dataset was divided by quarters each representing the four seasons, March 2014 to February 2020 defined as the prepandemic phase, March 2020 to May 2020 defined as the early pandemic phase, and June 2020 to August 2021 as the late pandemic phase. Patients with a principal discharge diagnosis of AMI were identified using ICD-9 and 10 codes. The number of AMI hospitalizations and crude 30-day mortality was calculated for each quarter. Results: Before the pandemic, number of AMI hospitalizations in the US were gradually declining from 48,258 per quarter in Q2 2017 to 42,639 in Q2 2019 (12 % decrease compared with 2017) with regular seasonal increases during the winter months (Q1). Thereafter, a sharp decline to 29,446 in Q2 2020 (31% decrease compared with 2019) was observed followed by a return to 34,105 in Q2 2021 (20% decrease compared with 2019). The crude 30-day mortality rate was 12.3% in the 12 months before the pandemic but increased to 13.3% in Q2 2020 during the early pandemic and remained the same at 13.3% after Q3 2020. Conclusions: In the US Medicare fee-for-service population, the number of AMI hospitalizations was in a steady decline before the pandemic, but dramatically declined during the first 3 months of the pandemic. In contrast, the crude 30-day mortality increased during the pandemic. Why these changes occurred remains a source of continuing investigation.
Abstract 17794: Rheumatoid Arthritis is Associated With Hypertension in Mendelian Randomization Analysis
Authors: Mackenzie N Samson, Quinn Wells, Matthew R Alexander
Journal: Circulation (2023)

Introduction: Epidemiologic studies have identified associations between multiple autoimmune diseases and hypertension. However, these studies can be biased by reverse causality and unmeasured confounding. Mendelian randomization (MR) is less susceptible to these biases and can provide insights into the etiological relationship between risk factors and outcomes. Question: Using MR, is there supportive evidence to suggest a causal relationship between autoimmune diseases and hypertension? Methods: Single nucleotide polymorphism (SNP)-based instrumental variables for type 1 diabetes mellitus, Crohn’s disease, ulcerative colitis, systemic lupus erythematosus, and rheumatoid arthritis were obtained from the NGHRI-EBI GWAS catalog of individuals of European ancestry using MR-Base, a database of instrumental variables derived from previously performed GWAS. The outcome was self-reported hypertension among UK Biobank participants with genome-wide genotyping of European ancestry. Two sample MR was performed using the TwoSampleMR R package, using the inverse variance weighted method with correction for linkage disequilibrium. Results: After correction for multiple comparisons using the false discovery rate, rheumatoid arthritis was associated with significantly higher odds of hypertension (beta= 0.0034, SE=0.0013, p=0.045). No significant associations were observed for type 1 diabetes mellitus (beta = 0.0046, SE=0.0023, p=0.103), Crohn’s disease (beta= 0.0023, SE= 0.0017, p= 0.267), ulcerative colitis (beta= -0.0014, SE=0.0011, p=0.267) and systemic lupus erythematosus (beta= -1.6x10 -8 , SE=0.0014, p=0.999). Sensitivity analysis using MR Egger revealed no significant confounding horizontal pleiotropy for the relationship between rheumatoid arthritis and hypertension (Egger-intercept= -0.0001, SE=0.0003, p=0.677). Conclusion: Using MR, a causal association was suggested between rheumatoid arthritis and hypertension. There was no evidence for an etiologic relationship observed with other autoimmune disease exposures tested. These findings suggest a role for rheumatoid arthritis in promoting hypertension development, which we theorize may be through enhanced immune activation.