tbuckley/cabot-search huggingface dataset:
Abstract 12698: Myocardial Infiltration of the Epicardial Adipose Tissue in Human Heart Failure
Authors: Anissa Viveiros, Kemar J Brown, Huachen Chen, Anran Zhang, Mobin Khoramjoo, Yuri Kim, Jonathan G Seidman, Christine E Seidman, Gavin Y Oudit
Journal: Circulation (2023)

Introduction: The epicardial adipose tissue (EAT) is adipose tissue that is contiguous with the myocardium without barrier. However, there is a fundamental gap in knowledge for the EAT’s role in health and disease. Methods: We employed single-nucleus RNA sequencing (snRNAseq) and molecular techniques to phenotype human EAT procured from patients with heart failure (HF) secondary to dilated cardiomyopathy (DCM) and ischemic heart disease (IHD). EAT was harvested from the right and left ventricles (RV and LV) of 10 healthy control (CTRL) donors ((median age: 54.0 (interquartile range [IQR]: 49.0-57.9) years; 5 [50.0%] males; median BMI: 25.0 ([IQR]: 24.5-28.2) kg/m 2 ), 32 DCM patients ((median age: 55.0 (interquartile range [IQR]: 48.0-60.7) years; 16 [50.0%] males; median BMI: 26.1 ([IQR]: 23.0-30.3) kg/m 2 ) and 22 IHD patients ((median age: 57.5 (interquartile range [IQR]: 52.5-64.5) years; 13 [59.1%] males; median BMI: 27.2 ([IQR]: 25.1-30.7) kg/m 2 ). HF patients were age (p=0.668 (DCM); p=0.172 (IHD)), sex (p&gt;0.999 (DCM); p=0.712 (IHD)), and BMI (p=0.711 (DCM); p=0.515 (IHD)) matched to CTRL. Results: There was a significant expansion of EAT over the LV (mean EAT thickness in CTRL: 1.11mm, DCM: 2.75mm (p=0.002) and IHD: 3.31mm (p&lt;0.001)) and the RV (mean EAT thickness in CTRL: 2.24mm, DCM: 5.57mm (p=0.029) and IHD: 5.11mm (p=0.065)) in HF. There was only a regional expansion of EAT over the LV of IHD patients. Data were analyzed using one-way ANOVA with Tukey’s post hoc test. Histological staining revealed myocardial EAT infiltration in HF, which was absent in CTRL. Nuclei isolated from EAT and adjacent myocardium were then subjected to snRNAseq. The transcriptional signature of HF intramyocardial adipocytes closely resembled unique cell states and gene expression identified in the EAT, suggesting infiltration by the EAT. By contrast, myocardial adipocytes in CTRL tissue were distinct from the EAT. The adipocytes in the interventricular septum, which lacks contiguous EAT, were similar in HF and CTRL. Conclusion: The proximity of the EAT confers a unique position to directly modulate the myocardium. As such, targeting pathogenic EAT expansion and infiltration may be critical to the development of novel therapeutic strategies in HF patients.
Abstract 18812: Premortem Risk Assessment Among Countywide Sudden Deaths
Authors: Kosuke Nakasuka, David Eik, Matthew Yee, Brielle Kinkead, Andrew Connolly, Ellen Moffatt, Zian Tseng, MD
Journal: Circulation (2023)

Introduction: Heart failure (HF) and left ventricular ejection fraction (EF) assessment have been hallmarks of sudden cardiac death (SCD) risk stratification for over 20 years. However, their sensitivity, specificity, and positive predictive value (PPV) for true arrhythmic death in the general population are unknown because nearly all SCD studies presume arhythmic causes. Aims: To define sensitivity, specificity, and PPV of current SCD risk stratification criteria for the autopsy-confirmed arrhythmic cause among countywide sudden deaths. Methods: POST SCD (POstmortem SysTematic Investigation of Sudden Cardiac Death) is a prospective cohort study using autopsy, clinical records, and toxicology to adjudicate arrhythmic (SAD; potentially rescuable with implantable defibrillator) or non-arrhythmic (non-SAD; e.g., tamponade, overdose) causes among presumed SCDs (pSCDs) in San Francisco County. We analyzed sensitivity, specificity, and PPV for syncope, EF≤35%, diagnosed HF, or the presence of any of 3 factors to discriminate SADs among pSCDs. Results: Between February 2011 and September 2022, 845 of 904 (93%) pSCDs 18-90 years had complete medical records available, of which 491 (58%) were SADs. Seventy-three pSCDs had history of syncope, with similar prevalence in SADs and non-SADs (p=0.4), while prevalence of HF was higher in SADs vs. non-SADs (88/491[18%] vs. 39/354 [11%], p=0.003). EF assessment was performed in 206 pSCDs (24%, 133 SADs, 73 non-SADs); prevalence of EF ≤ 35% was similar between SADs and non-SADs (p=0.112). A greater proportion of SADs had ≥1 factor than non-SADs (122/491[25%] vs. 65/354 [18%], p=0.015). Sensitivity of syncope, EF≤35%, HF, ≥1 factor for SAD was 9, 26, 17, 25%, specificity was 92, 82, 90, 82%, and PPV was 60, 73, 69, 65%, respectively. Conversely, 369 of 491 (75%) SADs had no risk factors before sudden death. Defibrillators were implanted in 4/491 (0.8%) SADs. Conclusions: In this 11-year countywide postmortem study, conventional risk factors had low sensitivity and PPV but high specificity for autopsy-confirmed arrhythmic cause of sudden death. Three-fourths of SADs had no risk factors before sudden death, highlighting the need for improved risk prediction in the general population.
Abstract 15748: Association of Clonal Hematopoiesis in the Setting of Human Immunodeficiency Virus Infection With Subclinical Atherosclerosis and Vascular Inflammation
Authors: Matthew S Durstenfeld, Katherine J Kentoffio, Alexandra J Teng, Shady M Abohashem, Danny Li, Yifei Ma, Rebecca Hoh, Steven Deeks, Alexander G Bick, Ahmed A Tawakol, Priscilla Y Hsue
Journal: Circulation (2023)

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is associated with cardiovascular disease (CVD) and common in HIV, but whether CHIP contributes to atherosclerosis in HIV is unknown. We hypothesized CHIP is associated with atherosclerosis and arterial inflammation among people with HIV (PWH). Methods: We studied treated, suppressed PWH ages 35-70 years old with ≥1 CVD risk factor. CHIP mutations were detected with a validated targeted sequencing assay. We measured carotid intima-media thickness (IMT) longitudinally with ultrasound and aortic inflammation and lymph node activity using cross-sectional 18 F-FDG-PET. Inflammatory biomarkers were measured with a multiplex electrochemiluminescence assay. We used linear regression with adjustment for age, sex, nadir CD4 count, smoking, hypertension, diabetes, and hyperlipidemia. Results: We included 231 PWH (52±9 years, 7% female). 32 (14%) had CHIP with median variant allele fraction of 3.1%. Common mutations were in DNM3TA (n=21) and TET2 (n=6). Only age was associated with CHIP (OR 2.3 per decade older, 95%CI 1.2-3.9; p=0.003). Among N=165 (CHIP=22), mean IMT was 1.0 mm with and without CHIP (p=0.63), unchanged after adjustment (Figure). CHIP was not associated with prevalent or incident plaque. Over 3.2 years, IMT progression was faster among those with CHIP (0.033 mm/year; p=0.10), attenuated after adjustment (0.022 mm/year; p=0.27). Among 80 with FDG-PET, CHIP (n=12) was associated with higher lymph node activity (SUV p=0.04) that was attenuated in reference to background activity and adjusted for risk factors. CHIP was not associated with arterial inflammation (p=0.83), inflammatory markers, or viral persistence markers. Conclusions: Among PWH, CHIP mutations were not associated with subclinical atherosclerosis or arterial inflammation, proposed mechanisms of how CHIP could cause CVD. Clinical outcomes studies are needed to ascertain the impact of CHIP on CVD in HIV.
Abstract 14125: Tricuspid Mass- Solving a Curious Case of Li-Fraumeni Syndrome
Authors: Tyler Huffaker, Anum Asif, Dawn Hui, Prince Otchere
Journal: Circulation (2023)

Background: Primary cardiac tumors are extremely rare (0.001-0.03%), but can have significant embolic, obstructive, and arrhythmic consequences. Li-Fraumeni syndrome (LFS) is an autosomal dominant genetic syndrome characterized by multiple malignancies, including osteosarcomas, CNS tumors, and adrenocortical, breast, and soft tissue sarcomas. We report diagnostic challenges of a patient with Li-Fraumeni syndrome found to have tricuspid valve mass and atrial septal defects. Case: 30-year-old female with Li-Fraumeni syndrome (ovarian cancer at 6 years,osteosarcoma and soft tissue sarcoma at 16 years, bilateral breast cancer at 26 years) found to have a tricuspid valve leaflet mass, as well as two atrial septal defects on surveillance echocardiography. There was concern for a primary cardiac tumor such as sarcoma or rhabdomyoma. She underwent surgical resection with biopsy showing organized mural thrombus. Decision making: Li-Fraumeni syndrome is a rare autosomal dominant cancer-predisposing syndrome, which can present with various tumor types. Cardiac tumors are extremely rare and have been limited to case reports. Although multimodality imaging is now more readily available, some cases remain diagnostic challenges if imaging is non-conclusive, histopathological studies remain the gold standard. In our case, the mass demonstrated mild enhancement in the post-gadolinium images suggestive for primary cardiac tumor versus a secondary metastatic cancer (Figure). A histopathological analysis by surgical resection demonstrated an organized thrombus. Conclusion: Diagnosis of cardiac masses in the setting of hereditary cancer syndromes such as LFS are rare and remain a challenge given the increased likelihood of primary or metastatic lesions. When imaging is inconclusive, further invasive investigations are warranted since it can alter the clinical management.
Abstract 17430: Targeting DNA Hypermethylation With Hypomethylating Drugs: Implications for Pulmonary Arterial Hypertension
Authors: EL-Kabbout Reem, ANTONELLA ABI SLEIMAN, MABROUKA SALEM, Sandra Breuils Bonnet, Alice Bourgeois, Sandra Martineau, Sarah-Eve Lemay, Charlotte Romanet, Charlie Theberge, Olivier Boucherat, Steeve Provencher, Sebastien Bonnet, Francois Potus
Journal: Circulation (2023)

Introduction: Pulmonary arterial hypertension (PAH) is a lethal vasculopathy characterized by sustained vasoconstriction and remodeling of pulmonary arteries. Excessive proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs) contribute to pulmonary artery remodeling, with limited efficacy of current pharmacotherapies. Increased DNA methylation (DNAm) has been implicated in pro-proliferative phenotypes and disease progression in cancer and cardiovascular diseases. Hypothesis: We hypothesized that increased DNAm contributes to the pro-survival phenotype of PAH-PASMCs and that targeting DNA methylation could improve PAH development. Methods and Results: Our study revealed a global increase of DNAm in remodeled pulmonary arteries of human PAH patients and three preclinical models (namely monocrotaline, sugen hypoxia, Fawn hooded rats, p&lt;0.05, immunofluorescence [IF] 5mc/SMA). In vitro, PAH-PASMCs exhibited elevated DNAm levels (IF 5mc, p&lt;0.05), increased expression of DNA methyltransferases (DNMT1, DNMT3a; Western blot [WB], p&lt;0.05), and decreased expression of DNA demethylase (TET2; WB, p&lt;0.05). Consequently, hypomethylating drug Zebularine demonstrated dose-dependent reductions in PAH-PASMC proliferation (WB for surviving, plk1, MCM2; IF ki67, p&lt;0.05) and increased apoptosis (WB for Bax/BCL2; IF annexinV, p&lt;0.05,). Transcriptomic and gene ontology analyses indicated that these effects likely involve the downregulation of biological processes related to the cell cycle and mitosis. In vivo treatment with Zebularine (10 mg/kg, 2 weeks, intraperitoneal injection) improved PAH hemodynamics (e.g., decreased RVSP, vascular resistances, p&lt;0.05), decreased PASMC methylation (IF 5mc/SMA, p&lt;0.05) and proliferation (IF ki67/SMA, p&lt;0.05), and mitigated adverse pulmonary vascular remodeling in two rodent models of the disease (monocrotaline and sugen hypoxia). Statistics: unpaired t test (2 groups), ANOVA (&gt; 2 groups). Conclusions: Our findings demonstrate an association between increased DNA methylation and PAH development. Targeting DNAm represents a potential therapeutic avenue for PAH, as evidenced by the beneficial effects of Zebularine in improving PAH-related phenotypes.
Abstract 15244: Synchronous Care in Cardiovascular Disease: The DECIDE-CV Clinic Program
Authors: Pedro Marques, Anahita Emami, Abdulkhaliq Alaamiri, Daniel Ho, Michael A Tsoukas, Thomas A Mavrakanas, Abhinav Sharma
Journal: Circulation (2023)

Background: The care model for type 2 diabetes (T2D) and its main complications is thought to be “asynchronous” and associated with delays in care and low use of guideline-directed medical therapies (GDMT). Hypothesis: A synchronous care clinic for T2D patients, including a simultaneous evaluation by cardiology/endocrinology and nephrology, will enhance the rate of GDMT use and improve biomarkers of interest. Methods: Retrospectively analysis from patients evaluated in the DECIDE-CV clinic, a cardiometabolic clinic for T2D patients with either atherosclerotic cardiovascular disease, heart fialure (HF) or chronic kidney disease (CKD). Baseline data was compared to the data obtained in the last available visit. For patients with only one visit, the treatment prescribed at the end of the first visit was considered in the last visit group. Categorical data is presented as frequencies (proportions) and was analyzed using McNemar test. Continuous data is presented as mean±SD or median (IQR) as appropriate and was compared using the t-test for paired data or Wilcoxon test. Results: 150 patients, 72% male with a mean age of 67±12 years. 115 (78%) had atherosclerotic cardiovascular disease, 98 (65%) had HF and 77 (51%) CKD. Comparing baseline to last visit data, there was a statistically significant increase in GDMT and de-escalation of insulin, sulfonylureas and DPP4i (Table). For patients with two sets of available laboratory data, there was a significant decrease in N-terminal pro B-type natriuretic peptide (504 [155-1160] pg/mL vs 335 [150-1031] pg/mL, p=0.03) and albuminuria (57 [19-259] mg/g vs 57 [9-155] mg/g, p&lt;0.01). Conclusion: A synchronous care clinic for T2D patients is associated with increased use of GDMT, de-escalation of therapy that lack morbidity/mortality benefit, and improvement in prognostic biomarkers. These results can potentially translate into better outcomes in this population.
Abstract 13467: Artificial Intelligence Guided Coronary CT Angiography Impacts Care Beyond Conventional Assessment: The CERTAIN Trial
Authors: Nick Nurmohamed, Jason H Cole, Matthew J Budoff, Ronald P Karlsberg, Himanshu Gupta, Lance Sullenberger, Carlos Quesada, Habib Rahban, Kevin Woods, Jeffrey Uzzilia, Scott Purga, Melissa Aquino, James K Min, James Earls, Andrew Choi
Journal: Circulation (2023)

Background: Atherosclerosis imaging-quantitative CT angiography (AI-QCT) guided by artificial intelligence has demonstrated high diagnostic accuracy for assessment of coronary atherosclerosis, stenosis and ischemia (AI-QCT ISCHEMIA ). Methods: CERTAIN was a multicenter study in 5 expert US centers prospectively recruiting 775 consecutive adult patients referred for CCTA. First, physicians were asked to complete an assessment of the patients’ diagnosis, additional imaging plan, intervention plan and medication management plan based on the conventional site assessment. Subsequently, coronary CT angiography (CCTA) exams were analyzed using AI-QCT, after which physicians were asked to repeat the assessment. Results: The 775 patients had a mean age of 64±12 years, 304 (39%) were female. Compared to site CCTA, AI-QCT analysis improved physician’s complete confidence two- to fivefold in every step of the care pathway (Figure). Overall, AI-QCT was associated with at least one clinical category change in over half (389; 50.2%) of patients compared to site CCTA interpretation, including CAD-RADS (304; 39.2%) and plaque burden (194; 25.2%). With implementation of AI-QCT, there was a 67% (43 vs. 14; p &lt;0.001) reduction in patients planned for myocardial perfusion imaging and a 48% (163 vs. 85; p &lt;0.001) reduction in patients referred for PCI or CABG compared to site CCTA. Conclusion: Implementing AI-QCT enabled a single-modality triple-aim assessment of stenosis, quantitative atherosclerosis and ischemia assessment through CCTA that improved physicians’ confidence, enhanced preventive medication uptake while it reduced the need for perfusion imaging and invasive testing.
Abstract 14237: Anticoagulation Strategies After Transcatheter Aortic Valve Implantation in Patients Without an Indication of Oral Anticoagulants, Network Meta Analysis of Randomized Controlled Trials
Authors: Ahmed K. Awad, Merihan A Elbadawy, Ayman K. Awad, Mohamed T Abuelazm, Shafaqat Ali, Basel Abdelazeem
Journal: Circulation (2023)

Introduction. Transcatheter aortic valve implantation (TAVI) is currently the mainstay treatment for aortic valve diseases, yet postoperative anticoagulation strategies after TAVI is still debatable. Thus, we aim to investigate the safety and efficacy of direct oral anticoagulants (DOACs) vs. single-antiplatelet therapy (SAPTs) vs. dual-antiplatelet therapy (DAPT) vs. Vitamin K antagonists (VKAs) in patients undergoing TAVI and without an indication of OACs. Methods: PubMed, Web of Science, Scopus, and Embase were systematically searched up to December 2022. A frequentist network meta-analysis has been conducted using a random-effects model calculating the odds ratio (OR) with a 95% confidence interval (CI). Results: We included 9,087 patients from 11 studies. Compared to DOACs, DAPT, SAPT, and VKAs were associated with significantly lower odds for short-term all-cause mortality (OR: 0.62; 95% CI [0.46-0.86]), (OR: 0.42; 95% CI [0.29-0.60]), (OR:0.54; 95% CI [0.31, 0.94]), respectively. DAPT was also associated with higher short-term major bleeding risk (OR:2.66; 95% CI [1.46-3.86]). Furthermore, both DAPT and SAPT were associated with significantly higher long-term bleeding rates with (OR: 1.78; 95% CI, [1.15-2.41]) and (OR:2.32; 95% CI, [1.29-3.35]), respectively. However, VKAs were associated with lower long-term bleeding rates (OR: 0.61; 95% CI, [0.24-0.98]). No intervention showed a significant difference over DOACs in terms of long-term all-cause mortality, cardiovascular mortality, and stroke, except for DAPT which showed higher odds of long-term all-cause mortality (OR: 1.83; 95% CI, [1.29-2.37]). Conclusion: Despite the long-term higher rates of major bleeding, SAPT was effective in preventing both short and long-term all-cause mortality compared to DAPT, which has both short, long term major bleeding and higher long-term all-cause mortality. Further RCTs are still required to confirm SAPT superiority compared to other strategies.
Abstract 17559: Spontaneous Coronary Artery Dissection (SCAD) Under Immune Checkpoint-Inhibitor Therapy
Authors: Andreas Spannbauer, Nika Skoro-Sajer, Carolina Dona, Rupert Bartsch, Wolfgang Lamm, Mariann Gyongyosi, Irene M Lang, Jutta K Bergler-Klein
Journal: Circulation (2023)

A 49-year-old female patient was admitted with symptoms of septic shock after her 8th cycle of neoadjuvant Carboplatin + Paclitaxel plus her 3rd cycle of Pembrolizumab for triple negative breast cancer in a curative setting. Despite empiric antibiotic therapy and fluid substitution the patient’s status continuously worsened necessitating a brief transfer to an ICU unit with catecholamine support. Levels of NT-proBNP (581pg/mL) and Troponin T (41ng/L) were measured on admission and massively increased to NT-proBNP 8038pg/mL and Troponin T 1044ng/L on the 2nd day. Sinus tachycardia, hypotension and lower extremity edema were apparent as signs of decompensated heart failure. Echocardiography showed moderate pericardial effusion, with preserved LV function and lack of wall motion abnormalities. Immune-checkpoint inhibitor (ICI) induced myocarditis was suspected. An MRI showed subendocardial late gadolinium enhancement (LGE) in the apex and midventricular wall, which was interpreted as either representing ischemic infarction or atypically distributed LGE due to ICI-associated myocarditis. An LVEF of 40%, as well as apical akinesia in the apex and midventricular sections consistent with apical ballooning as in Tako Tsubo syndrome were also observed. Angiography showed lesions consistent with spontaneous coronary artery dissection (SCAD) in the LAD and RCA. No PCI was performed. Over the next 2 weeks NT-proBNP and Troponin T continued to decline until discharge, and the patient stabilized with preserved ejection fraction. To summarize, this is a case of ICI myocarditis with concurrent SCAD and takotsubo-like left ventricular dysfunction.
Abstract 13412: Diagnostic Performance of Machine Learning on 12-Lead Electrocardiogram for Predicting Multi-Vessel Coronary Vasospastic Angina
Authors: Masato Shimizu, Takahiro Tsunoda, Eiko Sakai, Atsuya Shimizu, Yoshiki Misu, Tateishi Ryo, Masao Yamaguchi, Kato Nobutaka, Hiroshi Shimada, Ami Isshiki, Hidetoshi Suzuki, Hiroyuki Fujii, Makoto Suzuki, Mitsuhiro Nishizaki, Tetsuo Sasano
Journal: Circulation (2023)

Introduction: Multi-vessel coronary vasospastic angina (multi-VSA) is life-threatening disease. We tried to predict multi-VSA by machine learning (ML) on 12-lead electrocardiogram (ECG). Hypothesis: Machine learning on 12-lead ECG has powerful diagnostic value for multi-VSA. Methods: We recruited 227 consecutive sinus-rhythm patients (63.6±12.9years, 136men) who underwent acetylcholine-provocation test in coronary angiography (CAG). Multi-VSA was defined as spasm in at least 2 major branches. ECG was recorded before CAG in no chest pain period. ML was performed on table data of ECG parameters using several ensemble learning methods. Results: 79 patients (35%) showed multi-VSA, and univariate logistic regression analysis extracted 23 significant but weak predictors, the highest area under receiver operating characteristics curve (AUROC) was 0.673. Conversely, ML demonstrated high diagnostic performance (AUROC of extra trees classifier: 0.817). Shapley additive explanation method showed male, QTc, J wave in lead II, and low amplitude of Q wave in lead I/aVL played essential roles to build the ML model. Conclusion: Several parameters of 12-lead ECG in multi-VSA patients contains potential features of VSA, and their aggregation and ensemble learning can predict VSA with high diagnostic performance.