tbuckley/cabot-search huggingface dataset:
Abstract 17005: Brugada Syndrome: Is There a Difference Between Probands and Relatives?
Authors: James Scicluna, Jeanesse Scerri, Jessica Debattista, Christian Scerri, Mark A Sammut, Mark Abela
Journal: Circulation (2023)

Introduction: Brugada syndrome (BrS) is an inherited arrhythmic disease that is rarely linked to sudden cardiac death (SCD), often associated with SCN5A mutations. Hypothesis: The main objective of this study was to report the demographic, clinical findings and outcomes of a BrS registry in the Maltese Islands, comparing probands and relatives. Methods: Data was collected prospectively in all BrS patients. BrS was defined as per the latest European Society of Cardiology SCD guidelines published in 2022. Patients were placed in two groups (proband vs relative). Results: 120 individuals were included (2.7 per 10,000 individuals) (56.7% male, mean age 44.0±16.5 years at diagnosis, 7.5% athletes). 54 (45.0%) were probands. 61 (50.8%) reported cardiac symptoms. A relevant family history of SCD was present in 55 (46.6%). Follow up period of 49.8 ± 33.3 months. A spontaneous type 1 brugada pattern was the primary method of diagnosis in probands (71.1%), ajmaline provocation in relatives (71.6%) (p&lt;0.001). Probands reported more symptoms (33.1% vs 17.8%, p&lt;0.0001), documented arrhythmias during holter monitoring (29.0% vs 9.3%, p=0.028), and manifested J /ST elevation during stress testing (14.0% vs 5.3%, p=-0.039). The age at diagnosis was similar for probands and relatives. Similar proportions of atrioventricular block (15.7%), prolonged QRS (10.2%), early repolarisation (12.8%), QRS fragmentation (5.6%), low QRS voltages (5.6%) and pathological TWI (8.3%) were observed in both groups. 18 (20.4%) were identified with a SCN5A mutation (P, LP, VUS as per ACMG criteria). 5 patients (4.2%) had a novel variant. 17 (15.3%) were referred for a VT study. 20 (16.7%) had an ICD implanted, more frequent in probands (34.0% vs 3.1%) (p&lt;0.001). 3 were implanted because of OHCA. 27 (22.5%) were implanted with an ILR, commoner in probands (33.3% vs 16.4%, p=0.047). Two patients (10% of ICD subgroup) had an appropriate ICD therapy. One patient is on quinidine because of refractory shocks. Conclusions: The prevalence of BrS in Malta is comparable to other studies. 20.4% (probands) had a SCN5A mutation. The higher incidence of symptoms, arrhythmias, abnormal response during exercise and ICD implantation in probands (vs relatives) may suggest they are a higher risk group.
Abstract 14694: An Uncommon Mass, in an Uncommon Location, in a Common Patient?
Authors: Ngozi Osuji, Cihan Caglayan, Jacqueline Levene, Ezza F Tariq, Joseph Franz, Rafic Farah, Derek Serna-Gallegos, Jeffrey A Fowler, Catalin Toma, Adam Olson, Barinder Hansra, Joshua E Levenson
Journal: Circulation (2023)

Background: Myeloid sarcomas (MS) are rare extramedullary tumors composed of mature or immature myeloid cells. The heart is an uncommon site for this neoplasm. Case Presentation: A 68-year-old woman with a remote history of acute myeloid leukemia (AML) and allogeneic stem cell transplant presented with dyspnea. Her oxygen saturation was 70% on room air. Transthoracic echocardiography (TTE) revealed a nonhomogeneous intrapericardial mass measuring 6.3 cm by 10.0 cm, invading the right atrium and compressing the right ventricle (Figure 1). Due to persistent hypoxia, additional investigation with agitated saline contrast revealed a right-to-left intra-cardiac shunt. Cardiac magnetic resonance imaging showed invasion of the right and left ventricles, extension into the superior vena cava, and encasement of the right coronary artery. Due to worsening hypoxemia, vasopressin infusion and inhaled epoprostenol were initiated to reduce intracardiac shunting. Direct cardiac mass biopsy was considered prohibitive risk, however, a pericardiocentesis allowed for cytologic analysis of pericardial fluid which revealed atypical white blood cells, and subsequent flow cytometry indicated an aberrant myeloid population with monocytic features consistent with MS. She initiated chemotherapy with decitabine and low dose cytarabine. On day 6 of chemotherapy, she started external beam radiation therapy. A repeat TTE on day 10 of therapy showed a marked reduction in tumor size and intracardiac shunting. Discussion: MS can manifest before the development of bone marrow disease, following treatment for bone marrow disease, as relapse or progression of previous myelodysplastic or myeloproliferative neoplasms. With approximately fifty cases reported in the literature, most achieved temporary remission. Our approach to management included chemotherapy with decitabine and cytarabine and subsequent external-beam radiotherapy.
Abstract 16624: Patients’ Perspectives on the Impact and Management of Angina - Preliminary Results of the PACT-ANGINA International Survey
Authors: Giuseppe Rosano, Maria George, Juan-Carlos Kaski, magdy abdelaziz, Jabir Abdullakutty, Rajeev Agarwala, Francois Christory, Filippo crea, Nabil M Farag, Luis Henrique W Gowdak, Martha Gulati, Gustavo F Mendez, Dalton B Percoma, Jorge Daniel Sierra Lara Martinez
Journal: Circulation (2023)

Introduction: PACT-ANGINA is a quality improvement initiative aimed to improve the understanding of challenges in the management of angina and chronic coronary syndromes. Hypothesis: An international patient survey is conducted to assess how angina and its management affect patients’ lives and what patients want in terms of the management of their angina. Methods: A working group that included 9 cardiologists and 7 patient representatives developed an online, anonymous questionnaire. Patients with angina were invited to take part in the survey by patient organizations and treating physicians. Results: Between January and June 2023, the survey was completed by 891 patients in 21 countries. The proportion of female patients was 46%. Among participants, 57% had been diagnosed with angina for 2 years or less, and 54% had never undergone a percutaneous coronary intervention. The proportion of patients with no history of smoking was 65% and the most common self-reported concomitant diseases were hypertension (49%), diabetes (38%) and dyslipidemia (23%). Pain, tightness, pressure or discomfort in the chest (89%), shortness of breath (44%), and fatigue (39%) were the most frequently reported symptoms, and 34% of participants felt that their physical activities were very or extremely limited by angina symptoms. The proportion of respondents who felt that angina was having a great or extreme impact on their quality of life was 37%. When asked to rate the relative importance of 9 treatment objectives, respondents assigned the highest priority to 1) reducing angina attacks and symptoms, 2) avoiding hospitalizations, and 3) prolonging their life as much as possible. Among different aspects of care, those considered the most important by respondents to improve the management of their angina were 1) a better follow-up of their symptoms, 2) practical and easy-to-understand information, and 3) lifestyle changes counseling. Conclusions: This study demonstrates that patients with angina are often limited by their symptoms, which impact their quality of life. Patient-centered management of angina is necessary to improve clinical care of such a common cardiac condition.
Abstract 14876: Characterizing Regional and Global Effects of Epicardial Adipose Tissue on Left Atrial Function
Authors: Ali A Noorbaksh, Shiva Reddy, Aditi Shankar, James P MacNamara, Christopher M Hearon, Benjamin D Levine, Satyam Sarma
Journal: Circulation (2023)

Background: Obesity is associated with left atrial (LA) dysfunction. Excess epicardial adipose tissue (EAT) deposition is one potential mechanism for this dysfunction. However, it is unknown if the effects of EAT on LA function are mediated via adjacency to LA tissue or rather, represent effects of generalized cardiometabolic dysfunction, also common in obesity. We hypothesized EAT located around the LA would be associated with LA function compared to EAT located distally on the left ventricle (LV). Methods: ardiac MRI was performed in 54 middle-aged obese adults (n = 80, age 40-55 yrs) enriched for increased heart failure risk (N-terminal pro-B-type natriuretic peptide &amp;gt;40 pg/mL or high-sensitivity cardiac troponin T &amp;gt;0.6 pg/mL; visceral fat &amp;gt;2kg). EAT was quantified by tracing the area of LV EAT depots on short axis and LA EAT depots on long axis. LA strain was assessed by MRI feature tracking as reservoir strain during LV systole, conduit strain during early LV diastole, and contractile strain during late LV diastole. Linear regression was performed between EAT area and LA strain components. LA function was quantified by LA reservoir, conduit, and contractile strain. Results: LV EAT amount was 12 times higher than LA EAT (66.7 vs 5.3 cm 2 ). LA EAT was associated with decreased LA conduit strain (r = 0.37, 95% CI = 0.12 to 0.58, p = 0.006) and a trend towards lower reservoir strain (r = -0.26, 95% CI = -0.49 to 0.01, p = 0.058). There was no association with contractile strain. There were no relationships between LV EAT and LA function. Conclusion: Increased LA EAT was associated with worse LA strain. In contrast, LV EAT had no demonstrable effect on LA strain. Our results suggest LA EAT may have direct mechanical or paracrine effects on atrial tissue function and may be a therapeutic target for improving LA function in obese patients.
Abstract 17364: Lysyl Oxidase Inhibition Induces Acute Aortic Dissection Through Activation of Focal Adhesions and Mammalian Target of Rapamycin Signaling in Mice
Authors: Zhen Zhou, Pujun Guan, Ripon Sarkar, Zhouxuan Li, Dongchuan Guo, Xue Yan Duan, Callie S Kwartler, Dianna M Milewicz
Journal: Circulation (2023)

Introduction: Defective genes that predispose to acute aortic dissections (AADs) suggest that maintenance of aortic integrity requires mature extracellular matrix (ECM) and intracellular homeostatic contraction of smooth muscle cells (SMCs). Focal adhesions (FAs) link the ECM to SMC contractile units, and we sought to determine the role of SMC FA signaling in a mouse model in which AADs are induced by disrupting ECM with a lysyl oxidase inhibitor, β-aminopropionitrile (BAPN). Methods: C57BL/6J wild-type mice at postnatal day 21 (P21) were exposed to BAPN to induce AADs. All aortas were visually inspected at necropsy or tissue harvest. Proximal aortas were harvested for single-cell RNA sequencing (scRNAseq) at P35 and for immunoblot analyses at P24 and P35. Echocardiography, tail-cuff blood pressure, and histopathology analyses were performed on surviving mice at P49. Results: MELD analysis of scRNAseq data identified SMC clusters as the top altered cell type in BAPN-treated aortas. KEGG pathway analysis identified activated FA, along with Rho/ROCK and mTOR signaling, in the BAPN-treated SMC cluster. Immunoblots confirmed increased phosphorylation of FAK, MYPT1, mTOR, p70S6K, and S6RP in BAPN-treated aortas, and FAK inhibition blocked Rho/ROCK and mTOR pathways. Pharmacological inhibition of mTOR with rapamycin significantly rescued BAPN-induced AAD deaths (9% vs. 50%, p=0.001) without altering blood pressure, aortic enlargement, or aortic medial elastic fiber degeneration. Immunoblot analyses confirmed dramatic decrease of mTOR, p70S6K, and S6RP phosphorylation levels in BAPN aortas with rapamycin treatment. Administration of a ROCK inhibitor, Y-27632, significantly augmented type A AAD incidence (p=0.04) without altering blood pressure in BAPN mice, and immunoblot analyses identified increased mTOR signaling as early as P24 in BAPN plus Y-27632-treated aortas compare with BAPN group. Conclusions: Activation of FA and downstream mTOR signaling triggers AAD when the ECM is disrupted by BAPN, and mTOR inhibition significantly attenuates these deaths. FAs also activate Rho/ROCK, which is protective. These findings support that preventing mTOR signaling or augmenting Rho/ROCK signaling are therapeutic targets to prevent AADs.
Abstract 15340: Octacosanol Exerts Anti-Inflammatory Effects on Primary Human Aorta Endothelial Cells (HAEC) Induced With Lipopolysaccharides (LPS)
Authors: Jingrong Tang, Diego Lucero, Wenling Li, Huaitian Liu, Julia Kun, Denis Sviridov, Zhi-Hong Yang, Yosuke Mukoyama, Alan T Remaley
Journal: Circulation (2023)

Atherosclerosis is a complex process characterized by chronic systemic inflammation, endothelial dysfunction, retention of lipoproteins, plaque formation in large and medium-sized arteries, and has become one of the most common causes of death in the elderly nowadays. Octacosanol, a very long chain (C28) aliphatic alcohol, is believed to be the main active ingredient in the Policosanol, which is extracted from plants, such as sugar cane and wheat germ. Policosanol has been used as a potential diet supplementary to improve fatigue, obesity and lipid metabolism. Previous animal studies have shown that both Policosanol and Octacosanol can significantly ameliorate formation of atherosclerotic lesion. To further explore the possible mechanism of Octacosanol on the formation of atherosclerosis, we examined the anti-inflammatory effects of Octacosanol on HAEC treated with LPS at 100ng/ml FBS-free cell culture medium. LPS treatment significantly enhanced human monocyte (THP1) adherence to HAEC cells in time-dependent and dose-dependent style, but Octacosanol at 1.25 or 2.5 μM markedly blocked the adhesion of THP1 to HAEC. ELISA showed that LPS can significantly increase the expression of inflammatory cytokines and adhesion molecules by HAEC at 100ng/ml within 4 hours. LPS stimulated more than 3-fold of release of IL-6, IL-8, MCP-1 at 4 hours. By flow cytometry and ELISA, LPS dramatically increase the expression of PE-Selectin and VCAM-1. When HAEC were pretreated with Octacosanol (1.25μM or 2.5μM), it significantly reduced the release of inflammatory cytokines, MCP-1(p&lt;0.01), IL-6 (p&lt;0.001) and IL-8(P&lt;0.001), and inhibited the expression of PE-selectin(p&lt;0.001) and VCAM-1(P&lt;0.001). Confocal imaging analysis of HAEC cells showed Octacosanol considerably reduced the expression of PE-Selectin and VCAM-1 and VE-Cadherin, leading to the maintenance of cell membrane integrity and underlying ECM and the prevention of THP1 cell adherence. By RNAseq analysis, Octacosanol inhibits LPS-induced inflammatory pathways related to NFKB 2 and RAS-related signaling. In summary, the beneficial effects of octacosanol on atherosclerosis appears to be related, at least partially to, is potent anti-inflammatory effects in cytokine-induced cell adherence.
Abstract 14097: State-Wise Burden of Alcohol-Induced Cardiomyopathy in the United States From 1990-2019: Results From the Global Burden of Disease Study 2019
Authors: Stefan Milutinovic, Gautam Maddineni, Rolando Rodriguez, Ricardo O Escarcega
Journal: Circulation (2023)

Introduction: Alcoholic cardiomyopathy (ACM) causes 140,000+ alcohol-related deaths yearly. Alcohol consumption and the burden of ACM vary significantly across states within the US. Methods: To assess the burden of ACM in the USA, we used the Global Health Data Exchange. Adult alcohol per capita consumption was obtained from the National Institute on Alcohol Abuse and Alcoholism. Results: Over 30 years, ACM prevalence increased by around 53.15%, reaching 198000(k). Only three US states experienced a decline in the Age-Standardized Prevalence (ASP): the District of Columbia (DC), Maryland, and Virginia. New Hampshire and Utah had the highest and lowest ASP rates, correlating with per capita alcohol consumption. Notably, total US deaths decreased by 9.7%. This decrease is primarily due to a significant reduction in female mortality by about 70%, while mortality in men continues to increase steadily. In DC, Maryland, and Hawaii, females showed the most significant improvement, with DC having the highest reduction in Age-Standardized Death Rates (ASDR) by 83%. South Dakota had the lowest ASDR for both sexes, with 25.6% and 71.88% reductions in males and females, respectively. The Age-Standardized rate of Disability-Adjusted Life Years (ASDALYs) in the US has shown a slight downward trend and has decreased to 174k. However, ASDALYs for males increased by 8.5%. DC continues to have the highest ASDALYs, but with a significant reduction (64%), while South Dakota remained the state with the lowest ASDALYs per 100k, dropping from 35.3 to 22.84. Conclusions: Significant disparities were observed among states, with a higher burden in males. However, these trends were not as pronounced among females, except for increased prevalence. Notably, states with higher per capita alcohol consumption showed a more significant burden of ACM. Targeted interventions aimed at high-risk populations can play a crucial role in reducing the morbidity and mortality associated with this disease.
Abstract 15223: Clinical and Economic Impact of Patient Loss-to-Follow-Up After Short-Term Cardiac Monitor Usage in Cryptogenic Stroke
Authors: Klaus K Witte, Sarah C Rosemas, Karah Neisen, Paul D Ziegler
Journal: Circulation (2023)

Introduction: Short-term cardiac monitors (STMs) are increasingly used in the work-up of cryptogenic stroke patients before proceeding to long-term continuous monitoring for atrial fibrillation (AF) with insertable cardiac monitors (ICM). However, the rate of ICM placement after STM is only 4-5% based on large real-world studies. The impact of patient fall-out after STM on clinical/economic outcomes is unknown. Research Question: The objective of this analysis was to project the risk of additional ischemic strokes and stroke-related costs with varying rates of patient loss to follow-up (LTFU) after 48-hour, 14-day or 30-day monitors, compared to an approach of continuous ICM monitoring post-stroke. Methods: A previously published Markov model based on the CRYSTAL-AF trial was utilized to project lifetime ischemic strokes after various monitoring strategies, from a US payer perspective. Patient characteristics and AF detection rates were based on CRYSTAL-AF: diagnostic yield with the initial STMs were 0.8% for 48-hr, 3.1% for 14-day and 6.8% for 30-day monitors. AF detection resulted in a change from aspirin to DOAC, with subsequent risks of ischemic strokes and associated costs (including acute + post-acute care) modeled based on published literature. Results: Increasing rates of patient LTFU after STM were associated with higher projected additional secondary strokes compared to an immediate ICM approach, across all 3 STM types (figure). In the scenario based on real-world data (95% LTFU), a range of 62-68 additional strokes are projected per 1,000 patients, with associated stroke costs of $4,928-$5,449/patient when averaged across the population. Conclusions: Loss of patient follow-up after STM in real-world CS patients is projected to lead to substantial secondary stroke burden due to undetected AF, compared to continuous monitoring with ICM. Future work could focus on optimizing stroke pathways to ensure timely and continued access to monitoring.
Abstract 16712: Cardio-Ankle Vascular Index as an Independent Predictor of Cardiovascular Events in Patients With and Without Previous Cardiovascular Disease: A Systematic Review and Meta-Analysis
Authors: Hamed Tavolinejad, Julio A Chirinos
Journal: Circulation (2023)

Background: Large artery stiffness predicts the risk of major adverse cardiovascular events (MACE). However, most data to date are related to carotid-femoral pulse wave velocity. Data about the prognostic value of cardio-ankle vascular index (CAVI), a less blood pressure-dependent marker, are limited, especially among individuals without prior cardiovascular disease (primary prevention). Hypothesis: Higher baseline CAVI is associated with incident MACE and all-cause death. Methods: PubMed, Scopus, and Web of Science were searched up to 29 April 2023 for longitudinal studies reporting the association of CAVI with incident fatal and nonfatal cardiovascular events. Risk of bias was assessed using the MINORS tool. Pooled hazard ratios were calculated separately based on use of CAVI as a categorical or continuous variable. Subgroup analysis focused on studies of patients without prior cardiovascular disease. Results: We included 21 studies (37,658 participants; mean age range 52-75 years; 53.9% males). Median study follow-up duration was 5 years (IQR 4.4-6; range 2-12.4). Despite variations in multivariable models, studies reported adjustments for conventional risk factors. Higher CAVI was associated with risk of MACE among all studies (categorical HR=1.45 [1.23-1.70], I 2 =51%; continuous HR=1.24 [1.15-1.33], I 2 =18%) and in primary prevention studies (categorical HR=1.48 [1.12-1.96], I 2 =67%; continuous HR=1.22 [1.12-.33], I 2 =25%). While CAVI was associated with all-cause mortality in the overall analysis (HR=1.34; 95% CI: 1.09-1.63, I 2 =41%), primary prevention studies did not show a significant association (HR=1.09; 95% CI: 0.9-1.32 I 2 =15%). Conclusion: CAVI holds promise as an independent predictor for MACE, including individuals without established cardiovascular disease. Further epidemiological studies are needed to better understand its prognostic role, normative values in different groups, and its role in primary prevention strategies.
Abstract 16000: β-arrestins Mediate Cardiac Infiltration of Cytotoxic CD8+ T Cells and Macrophages in Acute CVB3 Viral Myocarditis
Authors: Emilio Y. Lucero Garcia Rojas, Haoran Jiang, Vincent D'Anniballe, Daniella Galtes, Alyssa Grogan, Soonbo D Han, Howard A Rockman
Journal: Circulation (2023)

Introduction: In response to Coxsackievirus B3 (CVB3) infection, immune cells infiltrate the heart affecting viral clearance, tissue damage, and cardiac remodeling. However, the molecular mechanisms regulating the immune response during acute CVB3-induced myocarditis are not well understood. β arrestins (βarrs), scaffolding proteins that mediate G protein-coupled receptor internalization, desensitization, and signaling are known to regulate immune responses. Hypothesis: We hypothesized that the immune populations infiltrating the heart during acute CVB3 infection are dependent on βarrs. Methods: To test our hypothesis, 5- to 7-week-old mice lacking βarr1 (βarr1 KO; n=8), βarr2 (βarr2 KO; n=4), or C57BL/6 controls (WT; n=7) were injected intraperitoneally with 1x10 4 plaque forming units (PFU) of CVB3 or saline and immune cell populations were measured in the heart at 7 days post infection (dpi) using flow cytometry. Results: At 7 dpi, there was a marked increase in cytotoxic CD8+ T cells in hearts of WT mice that positively correlated with the level of viral infection as assessed by heart tissue PFU (slope= 1.34, Y-intercept= -3.77). In contrast, the degree of infiltration of CD8+ T cells was significantly blunted in βarr KO hearts over a broad range of heart PFU (βarr1 KO: Slope=-0.3, Y-intercept=1.65; p=0.03 vs WT; βarr2 KO: Slope=-0.32, Y-intercept= 1.3; p=0.003 vs WT). Helper CD4+ T cell populations remained unaltered at 7 dpi among all groups. Macrophages at 7 dpi were significantly reduced in βarr KO hearts over a range of PFU (WT: Slope= 18.6, Y-intercept -52.32; βarr1 KO: Slope= -5, Y-intercept=32; βarr2 KO: Slope=3.46, Y-intercept=-8.4; p=0.04 vs WT). To assess cardiac injury, we measured the level of apoptosis by TUNEL staining and found that CVB3 infected βarr KO hearts showed significantly fewer TUNEL positive cells than WT CVB3 infected controls (WT 8.7%± 2.74; βarr1 KO 1.7%±0.51; βarr2 KO 1.7%±0.37; p=0.04 vs. WT). Conclusions: These data indicate that βarrs participate in the cardiac infiltration of CD8+ T cells and macrophages in response to CVB3 infection and that blocking the action of βarrs may diminish the cardiotoxicity with the acute phase of CVB3-induced myocarditis.