tbuckley/cabot-search huggingface dataset:
Abstract P471: Mechanisms Controlling Regression Of Cardiac Fibrosis By Removal Of Pressure Overload
Authors: Lily Neff, An Van Laer, Catalin F Baicu, Michael R Zile, Amy Bradshaw
Journal: Circulation Research (2021)

Background: Antecedent conditions, like aortic stenosis, can induce left ventricular pressure overload (LVPO), that can lead to Heart Failure with Preserved Ejection Fraction (HFpEF). Myocardial fibrosis and stiffness are key characteristics of HFpEF. Cardiac fibroblasts are the primary cell type regulating ECM production and deposition. In previous studies, biopsies isolated at the time of SAVR surgery, to correct stenosis, and then at 1-year and 5-years post-SAVR showed reductions in hypertrophy and fibrosis demonstrating these processes can regress. However, cellular mechanisms, including fibroblast activity, are poorly defined. Objective: Define mechanisms that contribute to remodeling of ECM before and after LVPO. Methods: LVPO was induced using transverse aortic constriction (TAC). LVPO was relieved by removal of the band (unTAC) at 4 wks. Cardiomyocyte cross-sectional area (CSA), collagen volume fraction (CVF), and protein production was measured by histology and immunoblot for five time points: nonTAC, 2wk TAC, 4wk TAC, 4wk TAC+2wk unTAC, and 4wk TAC+4wk unTAC. Results: In response to LVPO, myocyte CSA increased by 23% at 2wk TAC and by 47% at 4wk. CVF increased by 64% and 204% at 2wk and 4wk TAC, respectively, versus nonTAC. In 2wk TAC hearts, SMA, a marker of fibroblast activation was increased as was production of two collagen cross-linking enzymes, lysyl oxidase (LOX) and LOXL2, in the absence of significant increases in markers of ECM degradation. After unloading, myocyte CSA decreased by 20% in 2wk unTAC versus 4wk TAC and CVF decreased by 38% in 4wk unTAC versus 4wk TAC. Coincident with decreases in CVF, levels of pro-MMP2 increased at 2wk unTAC as did levels of degraded collagen measured by collagen hybridizing peptide reactivity. Whereas markers of ECM deposition, LOX and LOXL2, were not increased in unTAC myocardium, a resurgence of SMA production occurred in 2wk unTAC. Conclusions: In LVPO hearts, hypertrophy was characterized by increases in myocyte CSA, greater CVF, and fibroblast activation with increased production of pro-fibrotic ECM. After unloading, hypertrophy and fibrosis significantly decreased accompanied by increases in ECM degrading activity and reductions in proteins that contribute to collagen assembly.
Abstract 11906: Frequency and Characteristics of Coronary Periarteritis: An Intravascular Ultrasound Study
Authors: Toshiyuki Tsubouchi, Hajime Ichiryu, Mizuki Takai, Ryota Tochibora, Takeshi Ishihara, Sae Tateyama, YUTO MASUDA, Susumu Endo, Tamami Yoshida, Misayo Hayashi, Genki Naruse, Akihiro Yoshida, Shingo Minatoguchi, Takatomo Watanabe, Toshiki Tanaka, Nobuhiro Takasugi, Yoshihisa Yamada, Hiromitsu Kanamori, Hiroyuki Okura
Journal: Circulation (2021)

Objectives: Recently, several case reports using intravascular ultrasound (IVUS) have demonstrated peri-vascular abnormal mass (PVAM) or tumorous lesions of the coronary artery as coronary periarteritis in patients with IgG4-related disease. The aim of this study was to clarify the frequency and characteristics of PVAM in human coronary arteries. Methods: We reviewed 655 coronary vessels in 481 patients who underwent PCI for de novo coronary artery lesions using IVUS from January 1, 2017, to June 30, 2020. PVAM was defined as low echoic abnormal structures with or without high echoic areas that surround the coronary arteries (exterior to media) in a crescentic or circumferential fashion. In addition to standard gray scale IVUS observation, radiofrequency derived tissue characterization of the PVAM was performed to identify tissue characteristics using integrated backscatter IVUS (IB-IVUS). Results: PVAM were identified in 4 of 481 patients (0.83%) and 5 of 655 vessels (0.76%), respectively. Mean age was 64 years and 3 were male. Clinical presentation was chronic coronary syndrome in 3 patients and acute coronary syndrome in 1 patient. Mean length of the PVAM was 33 mm (SD 16mm) and the arc was 360°, respectively. The IB-IVUS analysis of the PVAM showed that the lesion had a mixed green, blue and purple color-coded layer (figure), indicating the tissue characteristics similar to those of fibrous plaque and lipid pool. Conclusions: Coronary periarteritis was a relatively rare (&lt;1%) finding in patients with coronary artery disease who underwent PCI. Further study with larger sample size is needed to clarify prognostic impact of the coronary periarteritis.
Abstract 10397: Prevalence and Outcomes of Primary Cardiomyopathy in Marfan Syndrome
Authors: Brynn S Connor, Claudia A Algaze, Ronnie T Collins
Journal: Circulation (2021)

Introduction: Cardiovascular disease is the leading cause of morbidity and premature mortality in Marfan Syndrome (MFS), with ≥ 50% of patients developing a secondary, dilated cardiomyopathy from chronic valvular regurgitation. Apart from significant valvular disease, patients with MFS have evidence of systolic dysfunction, suggestive of a primary cardiomyopathy. However, prior cross-sectional studies have been limited by small sample sizes and short durations of follow-up. Our aim was therefore to determine the true prevalence and long-term outcomes of a primary cardiomyopathy in MFS. Methods: We performed a retrospective chart review of all adult patients with a confirmed diagnosis of MFS followed at Stanford Health Care. Those with significant valvular dysfunction (≥moderate aortic or mitral regurgitation), coronary artery disease, or prior cardiac surgery were excluded. Myocardial dysfunction (MD) was defined as a left ventricular ejection fraction (EF) &lt;55%, as assessed by echocardiography or on cardiac MRI. Genetic, sociodemographic, and potential cardiac risk modifiers were also recorded. Results: A total of 753 patients with confirmed MFS were identified and followed over a median of 8 years (IQR 4, 13). Of the initial cohort, 241 patients (47% male, 71% Caucasian) met inclusion criteria and defined the at-risk population. MD was present in 30 patients (12.4%), with a median age of onset at 32 years (IQR 24.5, 44.8), median EF of 50.9% (IQR 48.0, 53.8), and evidence of clinical heart failure (NYHA Class ≥2) in 10% of patients. There was no significant association with the majority of queried sociodemographic and traditional cardiovascular risk variables. MD was more commonly observed in patients with larger aortic root diameters (aortic root ≥ 4.0 cm: AOR=4.2, 95% CI=1.2-15.0, p=0.03); however, corresponding use of goal-directed medical heart failure therapies did not appear to be protective against the development of MD (p=0.5). Conclusions: Even in the absence of significant valvular pathology, MD is prevalent in MFS from a young age, indicative of a primary cardiomyopathy. While dysfunction is often subclinical and mild in nature, it can progress across the lifespan and appears to be refractory to standard medical heart failure therapies.
Abstract 12524: Very Long-term Mortality After St Elevation Myocardial Infarction (stemi) Complicated By Cardiogenic Shock
Authors: Gabriel Kanhouche, Jose Nicolau, Talia Falcão Dalçoquio, Mauricio Felippi de Sa Marchi, Roberto R Giraldez, Remo Furtado, Luciano Baracioli, Roberto Kalil Filho, Fabio de Brito Junior, Alexandre Abizaid, Henrique Ribeiro
Journal: Circulation (2021)

Introduction: About 5-10% of myocardial infarctions develop severe form of presentation, with cardiogenic shock (CS). Despite evidence showing higher in-hospital and short-term mortality in patients with STEMI complicated by CS, long-term follow-up data is lacking. Hypothesis: The aim of this study was to assess very long-term prognosis of survived patients with STEMI complicated by CS. Methods: STEMI patients (n=1,444) were included (1998-2017) and followed for up to 17.6 years (median 5.4 [2.5-9.9] years). Long-term survival was assessed by Log-Rank test. Results: Compared to STEMI without CS, patients who presented CS (n=118) had no significant differences regarding age (62.0 ± 11.8 vs. 60.7 ± 12.7; p=0.31) and female sex (28.0% vs. 25.1%, p=0.51), but had lower left ventricle ejection fraction (38.8±13.0% vs. 49.7±13.1%, p&lt;0.001) and higher mean baseline creatinine levels (1.4±0.6mg/dL vs. 1.2±0.7mg/dL, p=0.002). Of note, CS patients presented higher in-hospital mortality (42.2%) compared to those without CS (OR=28.5; 18.1-44.7, p&lt;0.001). Long-term survival was lower in patients with CS (10.7±0.6 vs. 13.3±0.2 years, log rank =0.016). By multivariate analysis adjusted for baseline characteristics the main factors predicting mortality were age (HR=1.06; CI95% 1.05-1.07, p&lt;0.001), previous MI (HR=1.34;CI% 1.06-1.69, p=0.01), history of heart failure (HR=1.65; CI95% 1.15-2.37, p=0.007), stroke (HR=1.67; CI95% 1.12-2.47, p=0.01), diabetes (HR=1.41; CI95% 1.14-1.74, p=0.001) and the presence of CS (HR=3.65; CI95% 2.92-4.56, p&lt;0.001). Conclusions: In a very long-term follow-up after a STEMI, CS increased ~4-fold the mortality rates. After hospital discharge, CS remains an important independent risk factor for death in the follow-up. Our findings reinforce the importance of intensive clinical monitoring with optimal medical and non-pharmacological therapy for the remarkable risk factors in the very long-term post-STEMI complicated by CS.
Abstract 13721: Impact of COVID-19 Pandemic on Door-to-Balloon Time and Mortality Within a High Reliability STEMI System of Care
Authors: Weili Zheng, Grant W Reed, Chetan Huded, Anirudh Kumar, Kathleen A Kravitz, Amar Krishnaswamy, A M Lincoff, Stephen Meldon, Damon M Kralovic, Samir R Kapadia, Umesh N Khot
Journal: Circulation (2021)

Background: The COVID-19 pandemic is associated with delayed revascularization and worse clinical outcomes for patients with ST-Elevation MI (STEMI). The purpose of this study was to evaluate whether a comprehensive STEMI protocol (CSP), which improved door-to-balloon times (D2BT) and mortality prior to the pandemic, mitigated the pandemic’s negative effect on STEMI care and outcomes. Methods: We performed a prospective, single-center, registry-based study of 433 patients who received PCI for STEMI though an established CSP. We compared D2BT and in-hospital mortality of the period immediately prior to the pandemic (control period; 1/1/19 -3/14/20, N=291) with the period from 3/15/20 to 12/31/20 (study period, N=142), in-line with the declaration of a state of emergency by the state of Ohio. Results: Between control and study period, patients were similar in regards to age (61.2 +/- 12.0 yrs vs. 61.7 +/-13.2 yrs), female sex (32.3% vs 30.3%), nonwhite race (30% vs 26%), smoking status, BMI (30.4 +/- 8.9 vs 29.9 +/- 6.3), and other comorbidities. There was no significant difference in % meeting D2BT goals for STEMI (&lt;=90 minutes for ED and in-hospital, &lt;=120 minutes for hospital transfer patients) during control and study periods (79.0% v 78.9%, p = 0.97). When stratified by STEMI presenting location, there was no significant difference between control and study period D2BT for patients presenting in primary ED (48 min [IQR 36-66] vs 60 min [IQR 42-73], p = 0.09), as hospital transfers (96 min [IQR 79-119] vs 95 min [IQR 80-112], p = 0.86), or from in-hospital locations (95 min [IQR 80-112] vs 95.8 min [IQR 52-120], p = 0.50). There was no significant difference in in-hospital mortality between the control and study periods (4.5% and 2.1%, p = 0.22). Conclusions: Despite the profound effect of pandemic on overall health care operations, there was little overall change in STEMI process and outcome metrics within a high reliability CSP.
Abstract 12131: Improved Knowledge and Confidence of Antiarrhythmic Drugs in Atrial Fibrillation via Online Educational Intervention
Authors: Margaret Harris, Walid Amara, Lih-Fan Chang, Michael Lacouture, Philippe Guedj
Journal: Circulation (2021)

Background: Antiarrhythmic drugs (AAD) are currently used for the management of patients with arrhythmias. Despite randomized trial and real-world data many physicians remain hesitant to select an AAD in the daily-life routine. Purpose: To determine if an online continuing professional development intervention could improve knowledge and confidence of cardiologists and primary care physicians (PCPs) related to real-world data for AAD. Methods: Cardiologists and PCPs electively participated in a video-based, 2-faculty educational panel discussion on AAD management of arrhythmias, including real-world data. Educational effect was assessed using a repeated pair, pre-assessment/post-assessment study design and a chi-square test assessed differences from pre- to post-assessment. P -values &lt; .05 are statistically significant. Cramer’s V assessed level of educational effect using the range of &lt; 0.06 (modest), 0.06-0.15 (noticeable), 0.16-0.26 (considerable), and &gt; 0.26 (extensive). Data were collected June 5, 2020 through July 20, 2020. Results: Overall significant improvements were seen after education for cardiologists (N = 367; P &lt; .0001; V = .359) and PCPs (N = 760; P &lt; .0001; V = .359). Pre-assessment, the average correct response rate was 32% for cardiologists and 29% for PCPs, while post-assessment average correct response rates increased to 68% and 61%, respectively. Significant improvements were observed in cardiologists’ and PCPs’ knowledge related to the effect of AAD on outcomes (Table). As a result of the education, 36% of cardiologists and 45% of PCPs had a measurable improvement in confidence regarding selection of appropriate antiarrhythmic therapy for patients with AF. Conclusion: The statistically significant improvements observed in this intervention demonstrate that participation in a video-based panel discussion improved the knowledge and confidence regarding real-world data for AAD regarding their effects on outcomes.
A Nanocoating Co‐Localizing Nitric Oxide and Growth Factor onto Individual Endothelial Cells Reveals Synergistic Effects on Angiogenesis
Authors: Hyejoong Jeong, Daheui Choi, Yoogyeong Oh, Jiwoong Heo, Jinkee Hong
Journal: Advanced Healthcare Materials (2021)

Abstract The delivery of nitric oxide (NO)—an intrinsic cellular signaling molecule—is promising for disease treatment, in particular to vascular diseases, due to its endothelial‐derived inherent nature. The limited diffusion distance of labile NO prompts researchers to develop various carriers and targeting methods for specific sites. In contrast to the apoptotic effect of NO, such as anticancer, delivering low NO concentration at the desired targeting area is still intricate in a physiological environment. In this study, the layer‐by‐layer assembled nanocoating is leveraged to develop a direct NO delivery platform to individual endothelial cells (ECs). NO can be localized to individual ECs via S ‐nitrosothiol‐bound polyacrylic acid which is a polymer directly providing an endothelial‐like constant level of NO. To increase angiogenic activation along with NO, VEGF is additionally applied to specific receptors on the cell surface. Notably, the survival and proliferation of ECs are significantly increased by a synergistic effect of NO and VEGF co‐localized via nanocoating. Furthermore, the nanocoating remarkably promoted cell migration and tubule formation—prerequisites of angiogenesis. The proposed unique technology based on nanocoating demonstrates great potential for conferring desired angiogenic functions to individual ECs through efficient NO delivery.
Abstract P387: Deceasing Tissue Stiffness Improves The Efficacy Of Extracellular Matrix-based Therapy For Myocardial Infarction
Authors: Xinming Wang, Samuel Senyo
Journal: Circulation Research (2021)

Hypothesis and objective: We hypothesize that lowering heart stiffness improves heart regeneration induced by extracellular matrix (ECM) proteins. In this study we investigated heart post-injury responses in non-regenerative mice hearts with modulated tissue stiffness and ECM hydrogel. The objectives are 1) determining if heart stiffness affects heart regeneration in response to extracellular biomolecules; and 2) identifying specific signaling pathways that regulate fibroblasts and cardiomyocytes mechanosensitivity to extracellular proteins. Methods: P5 mouse heart stiffness was modulated by BAPN and genipin injections. Solubilized porcine fetal ECM was injected immediately after ligating coronary artery. Heart function and histology were conducted on day 3 and week 3 post-myocardial infarction (MI). A mice ventricle explant model was used to investigate the molecular mechanisms. Results: Heart stiffness was lowered from 50kPa to 9kPa by BAPN and increased to 142kPa by genipin. We observed that fetal ECM treatment preserved cardiac output, reduced fibrosis, and promoted cardiomyocyte cell cycle activity. Decreasing tissue stiffness further improved the therapeutic efficacy of fetal ECM on heart post-MI response (Fig.1). Decreasing tissue stiffness lowered fibrosis in non-ECM treated MI control hearts, but did not affect the other aspects. Using a ventricle explant model of various stiffness, molecular evidence demonstrated that agrin-YAP signaling pathway is involved in the mechano-regulation of fetal ECM-induced heart regeneration. Agrin expression was elevated and cardiomyocyte YAP activation was not affected by changing tissue stiffness in control (no-ECM) mechano-modulated explants. However, YAP activation in fetal-ECM treated explants was increased by softening tissue. We also demonstrated that ECM hydrogel inhibits fibroblast to myofibroblast differentiation through CAPG protein.
Abstract 12388: Impaired Mitochondrial Bioenergetics is Associated With Progression of Right Ventricular Dysfunction in Pulmonary Arterial Hypertension
Authors: Peng Zhang, Alexander Vang, Denielli da Silva Goncalves Bos, Julia Feord, Thomas Mancini, Alexander Park, Gaurav Choudhary
Journal: Circulation (2021)

Introduction: Pulmonary arterial hypertension (PAH) has poor prognosis related to right ventricular (RV) dysfunction and failure. Yet, the underlying mechanisms of RV dysfunction remain unclear. Mitochondrial (mito) dysfunction and energy deficiency in RV have been implicated in RV dysfunction in PAH. A better understanding of RV mito function in PAH is critical in identifying novel therapies to improve RV function. Hypothesis: We hypothesized that impaired RV mito bioenergetics is associated with progression of RV dysfunction in PAH. Methods: PAH was induced in adult Sprague-Dawley (SD) or Fischer (CDF) rats by injecting 20 mg/kg SU5416, followed by exposure to 3 wks of hypoxia (10% FiO 2 ) and then 1-4 wks of normoxia. Control rats injected with vehicle were kept in normoxia. Echocardiography and hemodynamics were performed. RV tissues were collected for mito respiration assessments by high resolution O2K-FluoRespirometer (Oroboros), mito morphology assessments by electron microscopy, and biochemical assays. Results: PAH rats have increased RV systolic pressure, and RV systolic and diastolic dysfunction that ranged in severity from early PAH (1 wk SD), advanced PAH-mild to moderate RV dysfunction (7wks SD), to severe RV dysfunction (4 wks CDF - die of RV failure starting wk 5). Oroboros data show that mito complex I-coupled oxidative phosphorylation and maximal electron transfer capacity are significantly reduced in 7 wks SD rats (O 2 flux per mass: 216±21 vs. 90±19 and 209±22 vs. 91±22 pmol·s -1 ·mg -1 , respectively, control vs. PAH, P &lt;0.01, N=6 each), which are further reduced in 4 wks CDF rats. In parallel, RV ATP amount is significantly lower in PAH rats and is associated with increased apoptosis. There are no changes in mito membrane integrity by cytochrome c assays or in mito content by PCR. Mito size analysis show a significant increase in smaller mito in 4 wks CDF rats but not in 7 wks SD rats, suggesting increased mito fission in severe RV dysfunction. Conclusions: RV mito bioenergetics is impaired in PAH, progressively worsens with progression of RV dysfunction, and occurs prior to increased mito fission. Targeting bioenergetics may aid in developing new therapies to improve mito function and delay RV failure in PAH.
COVID-19 hospital activity and in-hospital mortality during the first and second waves of the pandemic in England: an observational study
Authors: William K Gray, Annakan V Navaratnam, Jamie Day, Julia Wendon, Tim W R Briggs
Journal: Thorax (2021)

We aimed to examine the profile of, and outcomes for, all people hospitalised with COVID-19 across the first and second waves of the pandemic in England.This was an exploratory retrospective analysis of observational data from the Hospital Episode Statistics data set for England. All patients aged ≥18 years in England with a diagnosis of COVID-19 who had a hospital stay that was completed between 1 March 2020 and 31 March 2021 were included. In-hospital mortality was the primary outcome of interest. The second wave was identified as starting on 1 September 2020. Multilevel logistic regression modelling was used to investigate the relationship between mortality and demographic, comorbidity and temporal covariates.Over the 13 months, 374 244 unique patients had a diagnosis of COVID-19 during a hospital stay, of whom 93 701 (25%) died in hospital. Adjusted mortality rates fell from 40%-50% in March 2020 to 11% in August 2020 before rising to 21% in January 2021 and declining steadily to March 2021. Improvements in mortality rates were less apparent in older and comorbid patients. Although mortality rates fell for all ethnic groups from the first to the second wave, declines were less pronounced for Bangladeshi, Indian, Pakistani, other Asian and black African ethnic groups.There was a substantial decline in adjusted mortality rates during the early part of the first wave which was largely maintained during the second wave. The underlying reasons for consistently higher mortality risk in some ethnic groups merits further study.