tbuckley/cabot-search huggingface dataset:
Abstract 14696: Blockade of CD47 Using a Novel Anti-CD47 Molecule, BRB-002, Attenuates Atherosclerosis in an ApoE Mouse Model
Authors: Rui Yun, Dongdong Feng, Caiaphas Ardoin, Ofelia Mata, Sharline Chen, Pavan Cheruvu, Nick J Leeper, Craig Basson, B Alexander YI
Journal: Circulation (2023)

Atherosclerosis is characterized by the deposition of lipoproteins in the vessel wall leading to inflammatory response, neointimal thickening, and occlusive plaque. Emerging data suggests that the cell surface marker CD47 is upregulated in atherosclerotic lesions. CD47 produces a ‘don’t eat me’ signal that prevents efficient clearance of diseased vascular cells by phagocytes (a process referred to as ‘efferocytosis’), and it has been hypothesized that dysregulated CD47 may contribute to expansion of atherosclerotic lesions by allowing the accumulation of inflammatory debris in the necrotic core. Blockade of CD47 has been shown to reverse this defect in efferocytosis and attenuate atherosclerosis in mouse models. Here, we evaluated the efficacy of BRB-002, a novel hybrid protein biologic inhibitor of CD47, in a mouse model of atherosclerosis. Four-week-old apolipoprotein E-deficient (ApoE -/-) male mice were fed a high fat diet for 12 weeks during which they were treated with BRB-002 at 2.5 mg/kg, BRB-002 at 10 mg/kg, or IgG isotype control (10 mg/kg) three times a week. Animals were monitored by serial measurements of hematologic parameters, pharmacokinetics, and CD47 receptor occupancy. After 12 weeks, mice were injected with a cathepsin B fluorescent probe and then necropsied to examine their descending aortas. Probes of cathepsin B activity have been used to detect atherosclerotic lesions and shown to correlate with areas of active inflammation and plaque burden. BRB-002 was generally well tolerated in ApoE -/- mice with similar hemoglobin, hematocrit, and red blood cell count between groups. Evaluation of aortas by cathepsin B activity showed that animals treated with BRB-002 at both 2.5 mg/kg and 10 mg/kg dose groups showed significantly decreased cathepsin B activity compared to mice treated with isotype control. These results suggest that blocking CD47 with BRB-002 can attenuate inflammation and atherogenesis in mice.
Abstract 16491: The Relationship Between Cardiovascular Health and 10-year Atherosclerotic Cardiovascular Risk in American Adults
Authors: Gowtham R Grandhi, Pamela L Alebna, Joaquin Ignacio Armendano, Erfan Tasdighi, Albert D Osei, Michael J Blaha, Anurag Mehta
Journal: Circulation (2023)

Introduction: Life’s Essential 8 (LE8) is a metric of overall cardiovascular health (CVH) while 10-year atherosclerotic cardiovascular disease (ASCVD) risk is routinely used to guide primary prevention. Yet, the relationship between LE8 and 10-year ASCVD risk is unclear. Hypothesis: CVH has an inverse relationship with 10-year ASCVD risk in adults aged 40–75 years from the National Health and Nutrition Examination Survey 2017-2020 cycle. Methods: Adults with ASCVD and data missing to calculate 10-year ASCVD risk and LE8 scores were excluded. LE8 score was estimated from the mean of LE8 components (scored 0 to 100), with scores ≥80, 79–50, and &lt;49 grouped into ideal, intermediate, and poor CVH, respectively. 10-year ASCVD risk was estimated using pooled cohort equation, with scores &lt;5%, 5–19.9%, and ≥20% grouped as low, borderline/intermediate, and high risk, respectively. The survey weighted chi-square and ANOVA analysis was performed. Results: We included 1,550 adults representing nearly 45 million US adults with a mean age of 57.8 years, 35.3% women. Overall, 35.4%, 42.3%, and 22.3% had low, borderline/intermediate, and high 10-year ASCVD risk, respectively. Low, borderline/intermediate, and high-risk individuals had a mean LE8 score of 68.2, 61.8, and 62.6 (p-value: &lt;0.001) while 18.1%, 7.4%, and 5.6% (p-value: 0.002) had ideal CVH, respectively. Diet, nicotine exposure, body mass index (BMI), and blood lipids metrics were very low across the risk groups (figure). Additionally, the mean blood pressure metric was 41.3 among high-risk and 61.1 among intermediate/borderline-risk individuals. Conclusions: The prevalence of ideal CVH is very low across all 10-year ASCVD risk groups primarily due to poor diet, nicotine exposure, high BMI, and high blood lipids. Since ASCVD risk is predominantly age-dependent and given comparable LE8 scores among borderline/intermediate and high-risk individuals, LE8 may denote an age-independent long-term/lifetime risk.
Abstract 17368: Burden of Cardiovascular Diseases in Haiti: Implications for Low-Income Countries
Authors: Lily D Yan, Rodney Sufra, Reichling St Sauveur, Marie Christine Jean-Pierre, Youry Macius, Alexandra Apollon, Rodolphe Malebranche, Michel Theard, Gerard Pierre, Jessy Devieux, Jennifer Lau, Nour Mourra, Nicholas Roberts, Rehana Rasul, Denis Nash, Myung Hee Lee, Gene F Kwan, Monika M Safford, Laure Adrien, Jean Patrick Alfred, Marie Deschamps, Patrice Severe, Daniel W FITZGERALD, Jean Pape, Vanessa Rouzier, Margaret Mcnairy
Journal: Circulation (2023)

Introduction: Although 80% of global cardiovascular disease (CVD) burden occurs in low- and middle-income countries, data from Black populations in these settings are scarce. We estimated the baseline prevalence of CVD using data from the population-based Haiti Cardiovascular Disease Cohort. Methods: Among urban Haitian adults ≥18 years, we collected data on demographics, health behaviors, psychosocial measures, anthropometrics and clinical exams including imaging and laboratory data at enrollment from 2019-2021. Prevalent cases of CVD were adjudicated using approaches guided by US and international cohorts. Multivariable Poisson regressions assessed relationships between risk factors and prevalent CVD. Results: Among 3,003 participants, median age was 40 years, 58.1% were female, and 70.2% reported income of &lt;$1/day. The most common risk factors were elevated blood pressure (30.4% hypertension, 23.0% prehypertension) and obesity (17.2%). Age-adjusted prevalence of CVD was 14.7% (95%CI 13.3%, 16.5%). Heart failure was the predominant disease with an adjusted prevalence of 11.9% (95%CI 10.5%, 13.5%), followed by stroke (2.4% [95%CI 1.9%, 3.3%]), angina (2.1% [95%CI 1.6%, 2.9%]), MI (1.0% [95%CI 0.6%, 1.8%]), and TIA (0.4% [95%CI 0.2%, 1.0%]). Of all heart failure, 80% had preserved ejection fraction, with a median age of 57 years. Heart failure was associated in a dose-response relationship with hypertension, and with obesity, diabetes, chronic kidney disease, depression, and stress. Conclusions: The burden of CVD in urban Haiti is primarily early-onset heart failure, with low prevalence of ischemic heart disease, challenging current global assumptions. These findings highlightunderscore the urgent need for local population-based epidemiologic data on cardiovascular disease and risk factors to inform health policy, planning and promotion.
Abstract 16773: The Association of Lp(a) and Standard Modifiable Cardiovascular Risk Factors (SMuRFs) With Incident Myocardial Infarction: The Mass General Brigham Lp(a) Registry
Authors: Arthur Shiyovich, Adam N Berman, Stephanie A Besser, David W Biery, Gurleen Kaur, Sanjay Divakaran, Avinainder Singh, Daniel M Huck, Brittany N Weber, Jorge Plutzky, Marcelo Di Carli, Khurram Nasir, Christopher P Cannon, James L Januzzi, Deepak L Bhatt, Ron Blankstein
Journal: Circulation (2023)

Introduction: Lp(a) is a robust predictor of coronary heart disease outcomes, with targeted therapies currently under investigation. However, there is a paucity of data regarding the risk of elevated Lp(a) in relation to other cardiovascular risk factors. Objective: To evaluate the association of high Lp(a) with standard modifiable risk factors (SMuRFs) for incident first acute myocardial infarction (AMI). Methods: This retrospective study utilized the MGB Lp(a) Registry which included patients ≥18 years with an Lp(a) measurement between 2000-2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasm, and prior known atherosclerotic cardiovascular disease (ASCVD). Diabetes mellitus, hyperlipidemia, hypertension, and smoking were considered SMuRFs. High Lp(a) was defined as &gt;90 th percentile and low Lp(a) as &lt;50 th . The primary outcome was fatal or non-fatal AMI. A combination of natural language processing algorithms, ICD codes, and laboratory data were employed to identify the outcome and covariates. Results: A total of 6,238 patients met the eligibility criteria. The median age was 54 (IQR: 43-65) years and 45% were women. Overall, 23.7% had no SMuRFs and 17.8% had ≥3 SMuRFs. Over a median follow-up of 8.8 (IQR: 4.2-12.8) years, the incidence of AMI increased in a stepwise manner with higher number of SMuRFs among patients with high (logrank p=0.031) and low Lp(a) (logrank p&lt;0.001). Across all SMuRFs subgroups, the incidence of AMI was significantly higher for patients with high Lp(a) vs. low Lp(a) (Figure 1). The risk of high Lp(a) was higher than the risk imposed by any of the SMuRFs and was similar to having two SMuRFs. Following adjustment for confounders and number of SMuRFs, high Lp(a) remained independently associated with the primary outcome (HR=2.9 (95%CI=2.0-4.3), p&lt;0.001). Conclusions: Among patients with no prior ASCVD, high Lp(a) is independently associated with increased risk for first AMI regardless of the number of SMuRFs.
Abstract 14741: Value of Coronary Artery Calcium Testing in Asymptomatic Individuals With Prediabetes: A Multi-Cohort Study
Authors: Mahmoud S Al Rifai, Mouaz Al-Mallah, Michael J Blaha, Jaideep Patel, John McEvoy, Khurram Nasir, Izza Shahid, Kershaw Patel, Garima Sharma, Jaume Marrugat, Helena Tizon, Raimund Erbel, Andreas Stang, Karl Joeckel, Nils Lehmann, Sara Schramm, Boerge Schmidt, Roger S Blumenthal, Salim S Virani, VIJAY NAMBI, Miguel Cainzos
Journal: Circulation (2023)

Background: The population of adults with prediabetes is growing worldwide. The value of coronary artery calcium (CAC) testing to assess ASCVD risk in this group is poorly defined. Methods: We pooled participants free of clinical ASCVD from 4 prospective cohort studies including the Multi-Ethnic Study of Atherosclerosis (MESA), Heinz Nixdorf Recall (HNR) Study, Framingham Heart Study (FHS), and Jackson Heart Study (JHS). Participants were classified as having euglycemia, prediabetes, and diabetes. Cox proportional hazards models were used to study the association between glycemia status and CAC burden and incident ASCVD, adjusting for potential confounders. Results: The study population included 14,780 participants with mean (SD) age 58 (11) years, 54% women, 57% White, 27% Black, and 16% Other. A total of 11,429 had euglycemia, 810 had prediabetes, and 2,207 had diabetes. The distribution of CAC is shown in Panel A. Among those with prediabetes, 31% had CAC &gt; 100. Individuals with prediabetes and CAC &gt; 100 had higher event rates than participants with diabetes and those with diabetes and a guideline indication for GLP1RA/SGLT2i therapy (Panel B). In adjusted analyses, compared to individuals with euglycemia, the HR (95% CI) for ASCVD was 0.70 (0.41, 1.19) for prediabetes and CAC=0, 1.10 (0.76, 1.06) for prediabetes and CAC 1-99, 1.80 (1.37, 2.38) for prediabetes and CAC≥100, 1.82 (1.56, 2.13) among those with diabetes and 1.69 (1,42, 2.02) among those with diabetes and an indication for GLP1RA/SGLT2i. Conclusion: CAC &gt; 100 is frequent among individuals with prediabetes and identifies a subgroup at very high risk of ASCVD events. Adjusted 10-year ASCVD risk among individuals with prediabetes and CAC ≥100 is similar compared to people with diabetes and those with a guideline indication for GLP1RA/SGLT2i. Future clinical trials should assess whether individuals with prediabetes and CAC ≥100 benefit from cardiovascular risk-reduction with GLP1RA and/or SGLT2i.
Abstract 18159: Cardiac Resynchronization Therapy Response Predicted by Tissue Characterization Using Cardiac Magnetic Resonance Imaging in Non-Ischemic Dilated Cardiomyopathy
Authors: Jaewon Oh, Se-Eun Kim, Daehoon Kim, Hee Tae Yu, Chan Joo Lee, Tae-Hoon Kim, Jae-sun Uhm, Hui-Nam Pak, Moon Hyoung LEE, BOYOUNG JOUNG, Seok-min Kang
Journal: Circulation (2023)

Introduction: Tissue characterization using cardiac magnetic resonance (CMR) is helpful for risk stratification in non-ischemic dilated cardiomyopathy (NIDCM). Hypothesis: This study aimed to investigate the predictive role of tissue characterization identified by CMR on cardiac resynchronization therapy (CRT) response. Methods: We retrospectively reviewed the patients who underwent CMR within 1 year before CRT implantation in NIDCM patients at a single tertiary center from January 2018 to September 2022. Late gadolinium enhancement (LGE), native T1, T2 and extracellular volume (ECV) were analyzed. CRT response was defined as a decrease in left ventricular end-systolic volume (LVESV) &gt; 15% or an increase in left ventricular ejection fraction &gt; 5% on TTE after at least 3 months after CRT implantation. Results: Among a total of 101 patients (mean age 66 years, 52.5% of male), 76 (75.2%) patients were defined as CRT responders. CRT responders had more LBBB (96.1% vs. 60.0%, p&lt;0.001) and longer QRS duration (156.0±178.5 vs. 167.0±176.5ms, p=0.005) compared with CRT non-responders. However, LGE burden (34.3 vs. 13.3%, p&lt;0.001), native T1 (1371.6 vs. 1336.8ms, p=0.033), T2 (45.9 vs. 42.1ms, p&lt;0.001), and extracellular volume (ECV, 36.8 vs. 31.0%, p&lt;0.001) were significantly higher in CRT non-responders. The area under the curve (AUC) to predict CRT response is the highest in LGE burden (0.817, 95% confidence interval [CI]: 0.710-0.925), followed by ECV (0.808, 95% CI: 0.711-0.905), T2 (0.779, 95% CI: 0.663-0.895), and native T1 (0.643, 95% CI: 0.520-0.766). After adjustment, LGE burden&gt;20% (odds ratio [OR]: 0.15, 95% CI: 0.02-0.71, p=0.024) and ECV &gt; 34% (OR: 0.13, 95% CI: 0.01-0.78, p=0.037) were independently poor CRT response predictors. Conclusions: The tissue characterization by using CMR is helpful to predict CRT response and clinical outcomes in patients with NIDCM, independently of conventional CRT response predictors.
Abstract 14213: A Retrospective Natural History Study of Danon Disease
Authors: Kimberly N Hong, Tarek Khedro, Emily Eshraghian, Jennifer Attias, Garrett Storm, Melina Tsotras, Isaiah Jackson, Elijah Ahmad, Quan M Bui, Sharon Graw, Luisa Mestroni, Eric Adler, Matthew Taylor
Journal: Circulation (2023)

Introduction: Danon disease (DD) is a rare X-linked dominant cardioskeletal myopathy caused by mutations in the lysosome-associated membrane protein-2 (LAMP2) gene. The purpose of this study is to characterize disease progression and outcomes in males and females with DD. Methods: Data were from the International Danon Disease Registry that includes patients from the United States and Europe consented between 2005 and 2022. Records were obtained from the first episode of care to the date of enrollment and included demographics, clinical characteristics and outcomes. Chi square and Wilcoxon testing were used for cross-sectional and mixed effects models used for longitudinal analyses. Data were censored after TXP or LVAD. Results: This study included 112 patients with a median follow up of 6.8 yrs (IQR: 2.5-12.8 yrs). Demographics and outcomes are in Table 1. Males were more likely to experience the combined heart failure outcome. At least mild ventricular dysfunction occurred in 30% of patients, and almost all patients had LV hypertrophy. Regarding arrhythmias, WPW and CIED placement were common. Over time, LVEF decreased in both sexes and LV wall thickness did not increase, although LV mass increased in males only. BNP, CPK and AST did not change. [Table 2] Conclusions: DD is a multisystem and progressive disease with potential for cardiac arrhythmias, progressive hypertrophy and ventricular dysfunction. Currently, there are no disease modifying therapies for DD, although gene therapy trials are underway. Understanding the natural history of DD is critical for informing patient selection of therapies, including heart transplantation and new gene modifying therapies.
Abstract 16660: Precision Diagnosis of Hypertrophic Cardiomyopathy: A New Definition of Inappropriate Hypertrophy
Authors: Hunain Shiwani, Rhodri Davies, Constantin-Cristian Topriceanu, Anjali T Owens, Betty Raman, Raffaello Ditaranto, Joao Augusto, Camilla Torlasco, Matthew Webber, Benjamin Dowsing, Rebecca Hughes, Inês Miranda, Walter Witschey, Elizabeth Thompson, Silvia Castelletti, Lia Crotti, Luigi Lovato, Alberto Ponziani, Konstantinos Moschonas, George Joy, Iain Pierce, Peter Kellman, Alun Hughes, Elena Biagini, Saidi Mohiddin, Luis Lopes, Victor Ferrari, Harold Litt, Gabriella Captur, James Moon
Journal: Circulation (2023)

Introduction: The definition of hypertrophic cardiomyopathy (HCM), unaltered for 50 years, requires unexplained left ventricular hypertrophy with a maximum wall thickness (MWT) ≥15mm in probands. However, this doesn’t consider age, sex and body-size which is inadequate for a precision therapy era. Aim: To develop a personalised definition of inappropriate hypertrophy using cardiac MRI and evaluate potential care implications. Methods: Healthy reference cardiac MRIs from the Framingham Heart Study, UK Biobank, and multiple healthy volunteer studies were analysed by a validated AI algorithm. Generalized additive mixed models accounting for age, sex, and body surface area (BSA) established a personalized hypertrophy threshold for MWT (&gt;95% prediction interval) and conditional Z-scores. We assessed the discordance in HCM diagnosis between a “≥15mm” and “personalized hypertrophy” threshold applied to the UK Biobank and clinical HCM cohorts. Results: In healthy subjects (n=5,255), 36% of MWT variation was explained by age, sex and BSA. In the UK Biobank (n=44,690), using ≥15mm, there is a substantial sex skew; 8% of males and 1% of females are classified as hypertrophic. With a personalized threshold, this reduces to 3% of males and 2% of females classified as hypertrophic. 17% of subjects have a predicted hypertrophy threshold of 15mm (with 46% predicted ≤ 14mm, 37% predicted ≥16mm). In clinical HCM cohorts (n=1,854) across 5 centres in 4 countries (UK, USA, Italy, Portugal), females had thinner hearts (17.7 vs 19.1mm; p&lt;0.001) but more relative hypertrophy evidenced by greater deviation (Z-scores) from their predicted MWT (5.4 vs 5.1; p=0.05). Conclusion: We propose a new, personalised definition for hypertrophy that mitigates for significant age, sex and BSA confounding inherent in a 15mm cut point. We have identified potential for under/over diagnosis in a population cohort and suboptimal risk stratification in smaller, younger and/or female HCM patients.
Abstract 16410: Burden of Delirium on Mortality and Healthcare Resources Utilization in Geriatric Patients Hospitalized for Acute Coronary Syndrome: 5-years Retrospective Cohort Study
Authors: Majd Al Ahmad, Laith Alhuneafat, Anas Al-Ahmad, Mohammad Hamza, Bharadwaj Satyavolu, Hafiza Hareem Waqar, ahmad jabri, Ahmad Al-Abdouh, Anas Alameh
Journal: Circulation (2023)

Introduction: Acute coronary syndrome (ACS) and delirium are frequently observed in the geriatric population. Nevertheless, the precise impact of delirium on ACS outcomes and resource utilization remains inadequately elucidated. Hypothesis: We aim to investigate the burden of delirium on the outcomes of geriatric patients admitted for management of ACS. Methods: This is an analysis of the National Inpatient Sample of the years 2016 to 2020. We identified patients &gt;= 65 years old who were admitted with a principal diagnosis of ACS. Outcome studied included mortality difference, and length of stay (LOS) and cost of care (COC) as indicatives of healthcare resources utilization. Regression analysis was performed to compare those that developed delirium vs. those that did not while adjusting for baseline characteristics and comorbidities Results: Out of 1,845,379 elderly patients admitted for ACS, 1.3% (24,090 patients) developed delirium. The delirium group did not experience higher rates of in-hospital mortality compared to the non-delirium group (aOR 1.022, p=0.69, 95% CI 0.916-1.140). However, elderly ACS patients with delirium had a longer length of stay (aMD 5.60 days, 95% CI 5.26-5.95, p&lt;0.001) and higher cost of care (aMD $84,512, 95% CI $77,168-$91,857, p&lt;0.001). Conclusions: Elderly patients hospitalized for ACS face extended hospital stays and higher costs of care when they develop delirium. These findings highlight the significant economic impact of delirium and emphasize the importance of preventive measures in elderly ACS patients
Abstract 17571: Lessons From Launching a Digital Health Trial for Hybrid Cardiac Rehabilitation
Authors: Chang H Kim, Mansi Nimbalkar, Nino Isakadze, Yumin Gao, Zane MacFarlane, Jie Ding, Ashley Broderick, Alexandra Bush, Jeanmarie Gallagher, Brittany Wiley, Jackie Lobien, Tara Reddy, Carlos Aguado, Preeti Benjamin, Brittany Neigh, Kerry J Stewart, Lena M Mathews, Erin Spaulding, Seth S Martin, Francoise A Marvel
Journal: Circulation (2023)

BACKGROUND: Despite the well-established benefits of cardiac rehabilitation (CR) for secondary prevention of cardiovascular disease, participation remains low due to limited supply and access barriers. We built a hybrid CR program that combines in-person and home-based CR (with smartphone app (Corrie Health), smartwatch, Bluetooth blood pressure monitor, and health coaching delivered over 12 weeks). We assessed this novel CR program in a pilot study at Johns Hopkins Hospital and applied the lessons learned to launch a randomized controlled trial (mTECH REHAB; NCT05238103) of hybrid versus traditional CR. METHODS: We examined pilot data from Nov 2022 to Feb 2023 for electronic health record (EHR) screening, bedside enrollment, technology onboarding, access to CR, and weekly health coaching. We identified barriers in the enrollment process which we then used to guide trial design and team organization. RESULTS: EHR screening yielded 1,270 candidates, among which 209 (16.5%) were eligible following chart review. Our team approached 106 (50.7%) at bedside and 20 (9.6%) were enrolled into the pilot study. Ten (50.0%) were lost to follow up, with reasons of: loss of interest (3), post-procedural complication (3), frailty requiring acute CR (1), no insurance coverage (1), follow up in external CR (1), and technology challenges (1). These findings informed trial design as follows: 1) pre-specified filters for cardiovascular procedures/surgeries were added to EHR screening; 2) remote enrollment pathway was added; 3) a 2-week run-in period was added to verify insurance and continued interest following hospital discharge; and 4) standardized workflows and specialized teams were developed for patient recruitment, technology onboarding, and health coaching. The mTECH REHAB trial was launched in Apr 2023. In the first 9 weeks, 851 patients were screened, 157 (18.4%) were eligible, 148 (94.2%) were able to be reached at bedside or via telephone, 41 (27.7%; 16 bedside, 25 remote) were enrolled, and 5 (12.2%) were lost to early follow up because of: loss of interest (3), post-procedural complication (1), and patient relocation (1). CONCLUSIONS: A pilot study can inform and improve the enrollment process in a multi-component digital health trial.