tbuckley/cabot-search huggingface dataset:
Abstract 12167: Cardiac-Specific Knockout of Myosin Phosphatase Targeting Subunit 2 Prevents Cardiac Fibrosis in a Connective Tissue Growth Factor-Dependent Manner in Mineralocorticoid Receptor-Related Hypertension Mice
Authors: Zhe Ye, Ryuji Okamoto, Hiromasa Ito, Rie Ito, Keishi Moriwaki, Mizuki Ida, Lupiya Kimena, Yusuf Ali, Celso E Gomez-Sanchez, Masaaki Ito, Kaoru Dohi
Journal: Circulation (2023)

Introduction: Myosin phosphatase targeting subunit 2 (MYPT2) is an important subunit of cardiac myosin light chain phosphatase (MLCP), which plays a crucial role in regulating the phosphorylation of MLC (p-MLC). Recent research has shown that cardiac MLCP plays an important role in cardiac fibrosis as a target of Rho kinase and protein kinase G. However, it is unclear how the loss of MYPT2 affects cardiac function and fibrosis. Methods: After the knockdown of MYPT2, HL-1 cells (murine cardiomyocytes) were incubated with aldosterone (ALDO) for 24h. Cardiac specific MYPT2 knockout (c-MYPT2 -/- ) mice were generated using the Cre lox system (αMHCMerCreMer; MYPT2 f/f ). Mineralocorticoid receptor (MR)-related hypertension mice were induced by the subcutaneous infusion of ALDO and 8% NaCl food for 4 weeks after uninephrectomy. Results: In HL-1 cells, ALDO increased connective tissue growth factor (CTGF) and MYPT2 and decreased the p-MLC in a dose-dependent manner. Knockdown of MYPT2 decreased CTGF. In mice model, the MYPT2 expression in the heart from MYPT2 -/- mice was decreased to less than 30% compared with MYPT2 +/+ mice. Heart rate, blood pressure, and cardiac systolic function were normal in c-MYPT2 -/- mice. Type 1 phosphatase catalytic subunit β was decreased and p-MLC was increased in c-MYPT2 -/- mice. Blood pressure elevation and left ventricular hypertrophy were observed in both MR-related hypertension mice, while no difference in heart size and the nuclear localization of MR in cardiomyocytes. However, ejection fraction and fractional shortening in echocardiography were higher in c-MYPT2 -/- than in MYPT2 +/+ in MR-related hypertension mice. After treatment of ALDO for 28 days, both global radial and longitudinal strain (GRS and DLS) were reduced in both c-MYPT2 -/- and MYPT2 +/+ mice, but the reduction in systolic and diastolic GRS and GLS strain rates were prevented in c-MYPT2 -/- mice compared with MYPT2 +/+ mice. Histopathology revealed fibrosis degree in c-MYPT2 -/- mice was lower than MYPT2 +/+ mice with decreased CTGF and increased p-MLC. Conclusions: Cardiac-specific deletion of MYPT2 resulted in a decrease of MLCP and an increase of p-MLC. MYPT2 deletion can prevent cardiac fibrosis and dysfunction in a MR-related hypertension model.
Abstract 12837: Studies of Suboptimal Low Density Lipoprotein Reduction Following Lipid Lowering Therapy on Cardiovascular Outcomes in Patients With Acute Coronary Syndrome
Authors: SHIMPEI FUJIOKA, Daisuke Shishikura, Hideaki Morita, Mariko Shiba, Masaaki Hoshiga
Journal: Circulation (2023)

Introduction: Current guidelines advocate achieving a fixed LDL-C target and attaining a more than half reduction of LDL-C levels. As the heterogeneity of response to lipid lowering therapy, effective LDL-C reduction is not achieved even in patients achieved a fixed LDL-C target. Aims: This study ought to investigate the clinical impact of suboptimal LDL-C reduction following lipid lowering therapy on cardiovascular outcomes in patients with acute coronary syndrome. Methods: A total of 561 consecutive ACS patients undergone PCI with measurement of LDL-C levels at the index of admission and 12 months after PCI were enrolled in the study. Based on the current guidelines, &lt;50% LDL-C reduction within 12 months were defined as suboptimal LDL-C reduction. The relationship between the suboptimal LDL-C reduction and cardiovascular events including the composite of cardiac death, myocardial infarction, target vessel reperfusion, and stent thrombosis was evaluated. Results: In the current study, under the use of lipid-lowering therapies (statin: 84.1 %; high intensity statin: 18.9 %, ezetimibe: 24.8 % and PCSK9 inhibitor: 1.2 %), 24.6 % of study population exhibited LDL-C &lt;1.4 mmol/L at 12 month after the index of PCI and 24.2 % achieved more than half reduction of LDL-C within 12 months. There were no significant differences in cardiovascular events between 2 groups according to LDL-C &lt; 1.4 mmol/L (23.2 % - 17.4 %, P = 0.15), whereas the MACEs were higher in the suboptimal reduction group than the optimal reduction group (24.9 % - 11.8 %, P= 0.007). Of note, even in patients with LDL-C &lt;1.4 mmol/L, the MACEs were highly observed in the suboptimal reduction group than the optimal reduction group (25.0 % - 12.4 %, P= 0.04). Multivariate analysis adjusting baseline LDL-C, HbA1c, sex and age revealed that suboptimal LDL-C reduction was an independent predictor of cardiovascular outcomes (HR: 0.7, 95% CI: 0.49-0.90). Conclusions: In addition to a fixed LDL-C target, more than half reduction of LDL-C following lipid lowering therapy is another relevant potential to reduce cardiovascular outcomes in patients with ACS.
Abstract 12316: Metrnl Deficiency Destabilized the Atherosclerotic Plaque and Increased the Risk of Acute Coronary Syndrome
Authors: Rong Huang, Fengling Lai, Siyu Hou
Journal: Circulation (2023)

Introduction: Metrnl has been recently identified as a myokine/adipokine that acts as an immune/metabolic regulator. Hypothesis: Metrnl might be exert an important role in acute coronary syndrome. Methods: Circulating Metrnl levels were evaluated in 983 subjects with acute coronary syndrome and healthy controls recruited from Jinan Central Hospital. Apolipoprotein E-deficient mice infected with Metrnl-silencing adenovirus were used for investigating the function of Metrnl in atherosclerotic plaques. The relevant molecular mechanisms were then explored in-vitro in siMetrnl transfected and Metrnl treated HUSMC cells. Results: We found circulating Metrnl levels were significantly decreased in patients with ACS as compared to healthy controls. Metrnl were inversely associated with the incident and recurrent risk of acute coronary syndrome after adjustment for traditional risk factors. Metrnl inhibition in HFD-fed ApoE-/- mice resulted in aggravated atherosclerotic lesions with an SMC-poor/macrophage-rich fibrous cap. Further study demonstrated that Metrnl downregulation increased whereas overexpression prevented SMCs apoptosis and lipid trans-differentiation. KIT/SRC/AKT signaling pathway is involved in the role of Metrnl for the regulation of SMCs fate. Conclusions: Our findings demonstrated that decreased circulating Metrnl levels might be a potential biomarker for identification of patients with increased risk of acute coronary syndrome. Metrnl protected against apoptosis and lipid trans-differentiation in SMCs and stabilized the atherosclerotic plaque, suggesting a potential target for the treatment of atherosclerosis.
Abstract 11876: Impact of Online Continuing Medical Education on Advancing Physician Knowledge and Confidence Around Dual-Pathway Inhibition for Patients With Peripheral Artery Disease
Authors: Margaret Harris, Anne Sendaydiego, Michael Lacouture, Catherine Capparelli, Raghu Kolluri, Manesh R Patel, Herbert D Aronow
Journal: Circulation (2023)

Background: Patients with PAD are at risk for MACE and MALE. Antithrombotic therapy, including DPI can improve patient outcomes. Physicians who care for patients with PAD may require education to improve knowledge and confidence around employing newer treatments. Purpose: This study was conducted to determine if online CME could improve physician knowledge and confidence of advances in DPI for the treatment of patients with PAD. Methods: The educational program consisted of a 15-minute online video-based rapid-fire discussion between 2 experts that launched March 24, 2021-March 24, 2022. Data were collected from participants on March 24, 2022. Four multiple choice questions were used; 3 assessed knowledge and 1 determined confidence with Likert-type scale. Endpoints were assessed using a repeated-pair design with pre-/post-assessment. A paired samples t-test was conducted on overall average number of correct responses for physician knowledge, and a McNemar’s test was conducted at the question level (significance level, P &lt; .05) for confidence. Results: 855 physicians completed the pre-/post-assessment out of 3,825 total physician learners (22%). Physician specialties included general cardiology (28%), vascular cardiology (15%), vascular surgery (15%), other surgery (20%), and primary care (22%). Overall, significant improvements were seen in knowledge of medical treatment for PAD (P&lt;.001), data for the use of factor Xa inhibition to treat PAD (P&lt;.001), and confidence in selecting antithrombotic therapy (P&lt;.001) (Table). Gains in knowledge and confidence were highest amongst vascular specialists compared with non-vascular specialists (Table). Conclusion: This study demonstrates the effect of a 15-minute online video-based CME discussion between 2 expert faculty on knowledge and confidence among providers caring for patients with PAD related to advances in antithrombotic therapy. Continued gaps were identified for future educational targets.
Abstract 12724: High Health-Related Quality of Life Among Survivors of Out-of-Hospital Cardiac Arrest: A Nationwide Survey From 2001-2019
Authors: Harman Gailan Hassan Yonis, Kathrine Kold Sørensen, Henrik Bøggild, Kristian Bundgaard Ringgren, Carolina Malta Hansen, Christopher B Granger, Fredrik Folke, Helle Collatz Christensen, Britta Jensen, Mikkel Porsborg Andersen, Vicky Joshi, Ann-Dorthe Zwisler, Christian Torp-Pedersen, Kristian Kragholm
Journal: Circulation (2023)

Background: Survival after out-of-hospital cardiac arrest has increased over the past two decades. However, little is known about the health-related quality of life of long-term survivors. Purpose: We conducted a nationwide survey to examine the long-term quality of life of out-of-hospital cardiac arrest survivors from 2001-2019. Methods: The study included all out-of-hospital cardiac arrest patients from the Danish Cardiac Arrest Registry between 2001-2019 who were alive in October 2020. Health-related quality of life was evaluated using the EuroQol health questionnaire (EQ-5D), SF-12 Health Survey (SF-12), and Hospital Anxiety and Depression Scale (HADS). Results: Of the 4,545 survivors, 2,552 (56.1 %) completed the survey. Respondent and non-respondent age was comparable (67 vs. 68 years). The median EQ-index score for survivors who had been alive for 0-1 year was 0.8 (Q1-Q3: 0.7-1.0), while survivors who had been alive for 15-20 years had a median EQ-index score of 0.9 (0.8-1.0). These scores were comparable to a Danish reference population, whose mean EQ-index score was 0.9 (SD: 0.16). Mean standardized SF-12 physical health score was 40.6 (SD: 12.7) for 0-1 year survivors vs. 44.4 (SD: 11.8) for &gt;15-20-year survivors, and the SF-12 mental health score was 53.1 (SD: 8.4) vs. 54.1 (SD: 8.7), respectively. Both scores were comparable to a Danish reference population. In terms of symptoms of anxiety, 73% of survivors who had been alive for 0-1 year reported a normal score (score ≤ 8), compared to 89.3% of survivors who had been alive for 15-20 years. For symptoms of depression, the percentages were 79.7% and 87.5%, respectively (Figure 1). Health-related quality of life was similar for survivor groups &gt;1-2, &gt;2-4, &gt;4-6, &gt;6-8, &gt;8-10, and &gt;10-15 years after arrest. Conclusion: Short-term as well as long-term survivors of out-of-hospital cardiac arrest generally reported high health-related quality of life after the event, regardless of the time elapsed since the arrest.
Abstract 12265: Evaluation of Aortic Valve Calcification in Patients With Suspected Cardiac Amyloidosis
Authors: Daniel Ng, Karine Moussa, Francis Allinson, Adam Behroozian, Timothy Jordan, Leah Puglisi, Curtiss Stinis, Paul Teirstein, Rajeev Mohan
Journal: Circulation (2023)

Introduction: Cardiac amyloidosis (CA) is characterized by the deposition of misfolded proteins within the heart causing a restrictive cardiomyopathy. Transthyretin (TTR) is one of the most common proteins implicated in CA, as well as in aortic stenosis (AS). The mechanism of TTR-CA associated AS is unclear. Hypothesis: We propose patients with severe AS being evaluated for transcatheter aortic valve replacement (TAVR) and suspected TTR-CA by echocardiogram will have an increased aortic valve calcium score. Secondary outcomes include post-procedural complications. Methods: This was a single-center, retrospective analysis of patients with severe AS referred to the Scripps system for TAVR between January 2017 and November 2022. A total of 496 patients were included and divided into two cohorts. The enriched (Likely CA) cohort consisted of patients with both IVS ≥1.2 cm and average mitral annular systolic s’ ≤ 6 cm/s. The unenriched (Unlikely CA) cohort met only one or none of the above echocardiographic criteria. Results: Of the 496 patients analyzed, 145 patients were in the Likely CA cohort and 351 patients were in the Unlikely CA cohort. Baseline demographics (Table 1A) and echocardiographic data (Table 1B) are shown. There was no statistically significant difference in the primary end point of aortic valve calcium score between the Likely CA and Unlikely CA cohort (p = 0.914). The Likely CA cohort had evidence of worse diastolic function and increased left ventricular dimensions. There was a non-significant trend towards an increased rate of post-procedural atrial fibrillation in the Likely CA cohort (p = 0.051). Otherwise, there was no significant difference in post-procedural complications between the two cohorts (Table 1C). Conclusions: In our analysis of patients with likely TTR-CA and AS compared to those with lone AS, there was no difference in aortic valve calcium score. This suggests aortic valve leaflet calcification is a process independent of TTR-CA.
Abstract 11536: Cardiac Magnetic Resonance Imaging Paralleled Recurrent Pericarditis Clinical Response to Rilonacept Treatment Over 18 Months: A RHAPSODY Subgroup Analysis
Authors: Paul C Cremer, Antonio Brucato, Antonella Insalaco, David Lin, Sushil A Luis, Deborah H Kwon, Christine L Jellis, JoAnn Clair, Allison Curtis, Sheldon Wang, Allan L Klein, Massimo Imazio, John F Paolini
Journal: Circulation (2023)

Introduction: Rilonacept treatment in RHAPSODY resolved active pericarditis recurrences, and long-term treatment led to sustained risk reduction. Prior analysis linked greater baseline Late Gadolinium Enhancement (LGE), with more rapid recurrence upon rilonacept suspension after 12 weeks of treatment. Serial cardiac magnetic resonance (CMR) imaging (T2-STIR, LGE) enabled longitudinal assessment for tracking clinical improvement, guiding decision-making, and predicting patient outcomes after treatment cessation. Methods: At the long-term extension (LTE) 18-month decision milestone (18MDM), investigators chose, based on clinical status, to continue rilonacept, suspend rilonacept/observe, or discontinue the LTE. An imaging core lab blinded to clinical data measured pericardial thickness and graded pericardial edema (T2-STIR) and LGE at baseline and 18MDM. Pericarditis recurrence was assessed clinically following rilonacept suspension. Results: Baseline and 18MDM CMRs were available for 13 patients. Reductions in pericardial thickness, T2-STIR, and LGE from baseline to 18MDM while on treatment are provided in Figure . CMRs were obtained in 7/8 patients suspending rilonacept at 18MDM: LGE was none/trace, and T2-STIR was negative; yet, 5/7 (71%) had pericarditis recurrence within 1-4 months of rilonacept suspension despite prophylactic colchicine (n=2). Conclusions: Continued clinical improvement during prolonged rilonacept treatment corresponded with improvement on CMR, including reduced pericardial thickness, resolution of pericardial edema on T2-STIR, and resolution of LGE. Negative/trace LGE at 18MDM while on treatment did not predict absence of pericarditis recurrence upon subsequent rilonacept suspension in this size-limited subgroup. Larger prospective studies examining CMR parameters in guiding RP treatment duration decisions and informing associated clinical outcomes are warranted.
Abstract 13734: Gender Differences in Authorship of Top Congenital Heart Disease Publications
Authors: Janice T Chua, Priya Pillutla
Journal: Circulation (2023)

Introduction: Despite progress in the representation of women in medical training, men continue to dominate fields such as academic medicine and cardiology. The proportion of female cardiology trainees and physicians has increased over time; however, women continue to be underrepresented in published cardiology literature. Research Question: Our study aims to investigate whether there are gender disparities in authorship amongst the top congenital heart disease publications. Methods: We performed a bibliometric analysis of publications indexed in PubMed from 2018 to 2022 from the top seven Cardiology and congenital heart disease (CHD) journals by impact factor and H5-index. The first authors, last authors, affiliations, and countries of origin were extracted. The genders of the authors were then determined from a database of name-to-gender mappings ( Gender API; gender-api.com ). One sample and independent sample t-tests were performed. Results: We identified 1058 CHD articles on PubMed which met the inclusion criteria. Female authors accounted for 38.1% of all first authors and 29.6% of all last authors, which was a statistically significant difference from the proportion of male authors (61.9% and 70.4%, respectively, p&lt;0.001). Europe showed a greater bias towards male first authors than the United States (p=0.010), whereas there was no significant gender difference seen in last authors between the two regions (p=0.170). Publications with a male senior author were more likely to have a male first author (67.1% male, p&lt;0.001), whereas there was no difference in first author gender in publications with a female last author (49.8% male, p=0.954). Conclusions: We analyzed the first and last author genders of publications in high-impact cardiology journals over the past 5 years and found that women are underrepresented in both first and last authorship positions. Patterns in underrepresentation emerged, both geographically and based on the gender of the senior author. Additional work is needed to address these gender disparities and identify concrete solutions to increasing female representation in CHD research, as it may elucidate obstacles to female representation in cardiology leadership, recruitment, and academic advancement.
Abstract 12276: The Mediating Effects of Insomnia Symptom Severity on the Relationship Between Acculturation Stress and the Prevalence of Hypertension Among Latinx Adults
Authors: Luciana Giorgio, Darwin Arias
Journal: Circulation (2023)

Introduction: Hypertension (HTN), a well-known risk factor for cardiovascular morbidity and mortality, affects about 44% of Latinxs in the US. Acculturation stress, a type of sociocultural stress, is associated with poor cardiovascular outcomes (i.e., HTN), in this population yet the mechanisms driving this association are understudied. Insomnia symptom severity(ISI) has been associated with increased acculturation stress and increased risk of HTN. So, ISI may drive the positive association between acculturation stress and HTN among Latinxs. We aim to examine the direct and indirect effects of acculturation stress on the prevalence of HTN via ISI among Latinxs. Hypothesis: We hypothesize that increased acculturation stress will be directly and indirectly associated with an increased prevalence of hypertension via increasing ISI. Methods: Using a sample of Latinx adults participating in the Hispanic Community Health Survey/Study of Latinos Baseline and Sueño Ancillary studies (n=1464), we conducted weighted unadjusted and adjusted bias corrected bootstrap tests of mediation. Acculturation stress was measured through the Hispanic Stress Index. ISI was measured through the Insomnia Severity Index. Hypertension was categorized as blood pressure &amp;gt130/80 or antihypertensive medication use. Adjustments for age, sex, nativity status, body mass index, and site were made. Results: Participants were M age=41.99 (SD=12.96). Most were women (53.76%), immigrants (65.44%), and of Mexican heritage (31.80%). Participants had a M ISI=7.38 (SD=6.49). About 39.01% were hypertensive. The total and direct effects of acculturation stress on the prevalence of HTN were statistically significant (PR=1.01, 95% CI: 1.00-1.02; PR=1.01, 95%CI: 1.00-1.02). ISI was a statistically significant mediator in the relationship between increased acculturation stress and increased prevalence of HTN in unadjusted models (Indirect effect=0.002, BCa 95% CI: 0.0002-0.004). Conclusions: Results suggest acculturation stress impacts HTN via increasing ISI among Latinxs. These findings should be replicated using longitudinal designs. If replicated, ISI may be an important target of intervention to mitigate the effects of acculturation stress on HTN among Latinxs.
Abstract 12822: Prediction of New-Onset Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy Using RNA-Sequencing of Plasma Small Non-Coding RNAs
Authors: Risako Yasuda, Keitaro Akita, Kohei Hasegawa, mathew S Maurer, Albree Tower-Rader, Michael A Fifer, Veli Topkara, Muredach P Reilly, Yuichi Shimada
Journal: Circulation (2023)

Background: It is known that about 20% of patients with hypertrophic cardiomyopathy (HCM) develop atrial fibrillation (AF), which can lead to stroke and worsening of heart failure. The current clinical model to predict new-onset AF in patients with HCM (HCM-AF score) offers only modest accuracy. RNA-sequencing (RNA-Seq) can determine concentrations of thousands of small non-coding RNAs (sncRNAs) in plasma. Hypothesis/Aims: To test the hypothesis that RNA-Seq of plasma sncRNAs predicts new-onset AF in HCM. Methods: In this prospective, multi-center cohort study, we conducted RNA-Seq of 3,740 plasma sncRNAs at enrollment on 283 patients with HCM without a prior history of AF. The outcome was new-onset AF. We developed a sncRNA-Seq-based LASSO classification model (sncRNA-Seq-based model) to predict new-onset AF using data from one institution (training set, n=193). We tested the predictive ability of the model in independent samples from the other institutions (test set, n=90). We also developed a clinical model with LASSO using all components of HCM-AF score - i.e., left atrial diameter, age, age at HCM diagnosis, and New York Heart Association functional class ≥2. We then compared the area under the receiver-operating characteristic curve (AUC) between the sncRNA-Seq-based model and the clinical model in the test set. Results: During a median follow-up of 2.8 [1.9-5.1] years, 25 patients (13%) in the training set and 7 (8%) in the test set developed new-onset AF. Using the sncRNA-Seq-based model developed in the training set, the AUC to predict new-onset AF in the test set was 0.82 (95% confidence interval [CI] 0.71-0.94, Figure ). This model outperformed the clinical model (AUC 0.59; 95% CI 0.38-0.81; Delong’s test P=0.02). Conclusion: This study serves as the first to demonstrate the ability of plasma sncRNA-Seq to predict new-onset AF in patients with HCM. The prediction model may help physicians identify patients with HCM who are at high risk of developing new-onset AF.