tbuckley/cabot-search huggingface dataset:
Abstract 17458: Diet Quality Mediates the Relationship Between Chronic Stress and Inflammation in Patients With Metabolic Syndrome
Authors: JungHee Kang, Debra K Moser, Terry Lennie, Misook L Chung, Travis Thomas, Martha J Biddle
Journal: Circulation (2023)

Background: Metabolic syndrome is associated with a two-fold increase in cardiovascular disease (CVD) outcomes. Chronic stress is related to poor diet and development of metabolic syndrome. Inflammation plays an essential role in metabolic syndrome and can be moderated by diet. Hypothesis: Diet quality mediates the relationship between chronic stress and inflammation in patients with metabolic syndrome. Methods: Participants with metabolic syndrome (n=73, 62±12 years old, 71% female) completed questionnaires on chronic stress (Perceived Stress Scale [PSS-10]) and diet quality (Healthy Eating Index [HEI-2015]). The PSS-10 was dichotomized (highest quartile -Higher stress group- vs. lower quartiles -Lower stress group-). The HEI-2015 is comprised of 13 dietary components. Higher HEI-2015 scores indicate better diet quality. Inflammation was assessed by plasma high-sensitivity C-Reactive protein (hs-CRP). We used the PROCESS macro to test mediating roles of HEI-2015 between chronic stress and hs-CRP (log-transformed). Results: Higher stress group had worse mean HEI-2015 scores (64 ± 10 vs. 57 ± 13, P = .02). Among the 13 dietary components, the greatest differences between higher and lower stress groups were fruits and vegetable component scores (P &lt; .05). As shown in Figure, diet quality mediated the relationship between chronic stress and inflammation (indirect effect = a*b = .211, 95% Confidence Interval [CI] = .006 to .496). Higher chronic stress group was associated with lower diet quality (a = - 7.152, 95% CI = - 13.168 to - 1.137), and, in turn, increased inflammation (b = - .030, 95% CI = - .052 to - .007). Conclusions: Our findings show the important role of diet quality in the relationship of chronic stress with inflammation in patients with metabolic syndrome. Increased intake of fruits and vegetables may be one of the most important recommendations for lowering inflammation and reducing CVD risks in highly stressed patients with metabolic syndrome.
Abstract 16361: Atypical Presentation of Myocardial Ischemia Provoked by Food Ingestion
Authors: Abdul Rahman Akkawi, Sana Imran, Sean-Mikael Dodenhoff, Abhiram Challa, Ahmad Mahdi, Freidy Eid
Journal: Circulation (2023)

Introduction: A type 2 myocardial infarction typically occurs due to demand ischemia from a blood supply mismatch. Significant blockage can trigger coronary steal syndrome and worsen perfusion in areas with severe coronary artery disease (CAD). In this case, we highlight a patient who experienced a dynamic elevation in troponin levels after food consumption, ultimately necessitating coronary artery bypass graft surgery (CABG), shedding light on the diverse presentations of cardiac ischemia. Case Presentation: A 49-year-old male with a history of hypertension, type 2 diabetes mellitus, obesity, recent stroke on dual antiplatelets, and non-obstructive CAD presented with chest discomfort over a period of two months. The patient denied associated symptoms and physical examination was unremarkable. Interestingly, the chest pain occurred specifically after meals. Extensive workup, including an EGD and CTA Abdomen, were negative. The symptoms were refractory to proton pump inhibitors (PPI). An EKG revealed dynamic precordial ST segment depressions, and troponin levels were elevated after meals on multiple occasions, gradually decreasing between meals. A left heart catheterization revealed severe five-vessel blockages; thepatient consequently required a quadrupleCABG. Following surgery, the patient reported a resolution of chest pain. Discussion: Our patient developed chest pain and demonstrated elevated troponin levels after each meal. With an extensive negative workup, further evaluation was necessary. Theoretically, circulatory flow in the splanchnic circulation during food digestion can mimic physical activity. Additionally, a full stomach may irritate the diaphragm and lead to arrhythmias. This case highlights the potential role of meals as triggers for coronary artery disease in patients with critical coronary blockage. Demand cardiac ischemia can manifest with atypical presentations that may pose diagnostic challenges. It is essential to recognize the atypical presentations of myocardial infarction to aid in the timely diagnosis and treatment of this potentially life-threatening condition.
Abstract 16702: Associations Between Knowledge, Attitudes, and Practices and Blood Pressure Control Among Iraqi and Syrian Refugees in the United States
Authors: Abeer Alharthi, Oluwabunmi Ogungbe, Rawnaq Behnam, Cheryl Dennison Himmelfarb, Yvonne Commodore-Mensah, tala al-rousan
Journal: Circulation (2023)

Introduction: Displacement due to war or persecution has resulted in an unprecedented refugee crisis. Refugees face increased cardiovascular disease risk and poor blood pressure (BP) control. Yet, insights into their knowledge, attitudes, and practices (KAP) influencing BP management are limited. Objective: To examine associations between KAP and BP control among Iraqi and Syrian refugees resettled in the United States. Method: Refugees from Iraq and Syria diagnosed with hypertension were recruited using a patient list at a federally qualified health center in San Diego. They completed a KAP survey and measured home BP (HMBP) using digital cuffs for at least 3 days/week for 4 weeks. Scores were computed for each KAP sub-scale; knowledge (0-16), attitude (1-20), and practice (1-8). Scores were categorized into quartiles (poor-excellent). The outcome was BP control calculated from an average of HMBP readings over 3 days for 4 weeks. Mixed effect logistic regression was used to assess the relationship between each KAP quartile and BP control (&lt;130/80 mmHg). Results: Final analysis included 95 refugees (79% Iraqis, 21% Syrians). Participants were male (56%), with mean age 58.4 (±16.34) years, 86% unemployed, 22% had at least a Bachelor's degree, 66% had limited English proficiency and only 3.6% had annual income ≥$35,000. The mean scores were as follows: BP 129/79 mmHg, with 61% having uncontrolled BP, knowledge 13.2 (± 2.37), attitude 14.6 (± 2.38), and practice 6.5 (± 1.17). Higher knowledge correlated with higher odds of BP control (adjusted Odds ratio (aOR): 1.89,95% Confidence Interval (CI): 1.39 - 2.55). Those who had fair and good attitude had lower odds of BP control (aOR: 0.63, 95% CI: 0.52 0.77; OR: 0.58, CI: 0.45 - 0.75) respectively (Table). Conclusion: Findings suggest poorer BP knowledge correlates with BP control in Syrian and Iraqi refugees who are receiving BP care. Tailored health interventions for refugees are needed to promote cardiovascular health equity.
Abstract 15856: Genetics, Pathologic Characteristics, and Burden of Lethal Hypertrophic Cardiomyopathy Among Countywide Sudden Deaths
Authors: Leila Haghighat, David Eik, Matthew Yee, Brielle Kinkead, Julianne Wojciak, Andrew Connolly, Francesca N Delling, Theodore P Abraham, Ellen Moffatt, Zian H Tseng
Journal: Circulation (2023)

Background: Annual incidence of sudden cardiac death (SCD) is reported at 1% in cohorts with known hypertrophic cardiomyopathy (HCM), but these estimates presume arrhythmic cause and miss occult cases dying before diagnosis. Hypothesis: Prospective surveillance and postmortem investigation of community sudden deaths will uncover the true burden of presumed SCD (pSCD) and arrhythmic death (SAD) attributable to HCM. Objectives: Determine characteristics and precise contribution of HCM to population pSCD and SAD. Methods: POST SCD (POstmortem SysTematic Investigation of Sudden Cardiac Death) is a prospective cohort study using autopsy, clinical records, and toxicology to adjudicate arrhythmic (potentially rescuable with implantable defibrillator) or non-arrhythmic (e.g., tamponade, overdose) causes among pSCDs 0-90 years in San Francisco County. We included all incident cases from 2/1/11-3/1/14 (n=525) and approximately every 3rd day from 3/1/14-9/1/22 (n=497). We identified HCM victims via 3 parallel approaches: 1) pathology criteria; 2) echocardiogram (TTE) review; 3) genetic analysis. Results: Of 1022 pSCDs in the 11-year study period, we identified 13 cases with HCM, yielding a 2% contribution to arrhythmic death burden: 10 met pathology criteria; 2 via review of 203 TTEs (missed on initial report); 1 with pathogenic ALPK3 mutation. Only 2 of 13 (15%) pSCDs with HCM had premortem diagnosis. A greater proportion of pSCDs with HCM had autopsy-confirmed arrhythmic cause than pSCDs without HCM (11/13 [85%] vs. 547/1009 [54%], p=0.03). HCM contribution to pSCD burden decreased with age (p=0.003), highest among victims &lt;35 years, accounting for 7.1% (6/84) of pSCDs and 9.4% (3/32) of SADs. Genetic testing of 317 consented pSCDs (5/12 meeting pathologic or TTE HCM criteria) yielded pathogenic mutations in 40% (2/5), and identified 1 additional case without clinical phenotype. Conclusions: In this 11-year countywide postmortem study, HCM meeting pathologic, clinical, or genetic criteria was associated with autopsy-confirmed arrhythmic cause of sudden death, accounting for 2% of SADs, highest in cases &lt;35 years. As 85% of cases were undiagnosed before pSCD, the true burden of HCM-related sudden death may be substantially underestimated.
Abstract 17676: An Electrocardiographic Deep Learning Model is Informative for the Prediction of Atrioventricular Block After Transcatheter Aortic Valve Replacement
Authors: Arjun Aggarwal, Jonathan Mayl, Liam Butler, Scott Thiesfeldt, Nisha Patel, Sanket Pattanaik, Abigail Thomas, Ethan Yohannan, Turgay Celik, Oguz Akbilgic, Prashant Bhave, David X Zhao
Journal: Circulation (2023)

Introduction: Atrioventricular block requiring a permanent pacemaker (PPM) is an important complication after transcatheter aortic valve repair (TAVR). While several risk factors have been identified, a clinically useful risk prediction algorithm has been challenging to develop. Furthermore, while artificial intelligence methods utilizing structured clinical data have been used, a deep learning approach using raw electrocardiogram (ECG) data is a novel method in this field. Research Question: The objective of our study was to develop an electrocardiographic artificial intelligence (ECG-AI) model to assess the risk of PPM placement after TAVR using only the pre-procedure ECG. Methods: We analyzed data from 651 patients that underwent TAVR at Atrium Health Wake Forest Baptist in the last 10 years. We obtained raw ECG files in XML format from General Electric (Boston, MA, USA). The ECG data were used as inputs within a convolutional neural network (CNN) model. The CNN was an adjusted residual network with a batch size of 64, had 100 epochs, and used Adam optimization with default parameters. The model was trained using a 5-fold cross-validation strategy on 80% of the data and validated on a 20% hold-out set. The CNN was supervised on need for new PPM within 30 days after TAVR. All model evaluations were performed on the hold-out set. Results: Of the 651 patients in our sample, 61 patients required PPM placement within 30 days after TAVR. The average age was 77.2±9 years and there were 260 females (40%). In our sample, 34/268 (12.7%) patients with self-expanding valves and 26/377 (6.9%) patients with balloon-expanding valves received a PPM. Results of our final model on the hold-out set yielded an area under the receiver-operator characteristic curve (AUC) of 0.74 (95% CI 0.56-0.92). The accuracy of our preliminary model was 77% with a sensitivity of 60% and specificity of 79%. Conclusion: Our ECG-AI model achieved a moderate AUC for the prediction of PPM after TAVR. This serves as a proof of concept that pre-TAVR ECGs alone are informative for prediction of PPM. Future work includes model optimization and adding demographic and clinical variables to refine and develop a robust predictive model with continual improvement of the accuracy for prediction of TAVR outcomes.
Abstract 17144: Pi3 Kinase Activation by Platelet-Derived Purified Exosome Product to Induce Angiogenesis
Authors: Skylar A Rizzo, Ryan Mahlberg, Ashley Amontree, Timothy E Peterson, Tyra A Witt, Mary Nagel, Monique Bagwell, Laura Becher, Sungjo Park, Michael Sabbah, D. Kent K Arrell, Mark Li, Parisa Kargaran, jialun li, Yoha Kim, Fabrice LUCIEN, Paul Stalboerger, Andre Terzic, steven moran, Atta Behfar
Journal: Circulation (2023)

Introduction: Platelets are heavily implicated in angiogenesis; however, the underlying mechanism remains relatively uncharacterized. The goal of this study was to evaluate the angiogenic potency of a platelet-derived regenerative exosome product (PEP) in an effort to develop a novel treatment for peripheral arterial disease. Here, we evaluated the mechanistic basis of PEP in angiogenesis and it’s use In Vivo in a rodent hind limb ischemia model. Methods/Results: Under Current Good Manufacturing Practices, conditioned medium from apheresis platelet cultures was purified to acquire the exosomes. PEP, enriched in exosome markers CD63, CD9 and Flotillin, induced human umbilical vein endothelial cell (HUVEC) proliferation, migration, and vascular tube formation In Vitro. Proteomic evaluation of PEP highlighted receptor tyrosine kinase (RTK) pathways and western blot validation demonstrated induction of phospho-MAPK and phospho-AKT following PEP treatment of HUVECs. Systematic evaluation of RTK receptor involvement was performed using small molecule inhibitors and receptor knock-down in HUVECs, ruling out RTK activation as a mode of action. However, small molecule inhibition of PI3 kinase demonstrated elimination of PEP-induced AKT phosphorylation and reduction in PEP-induced angiogenesis In Vitro measured by HUVEC proliferation and migration. In Vivo, evaluation of angiogenesis was performed in a rodent model of hindlimb ischemia treated with PEP embedded in fibrin glue (PEP/TISSEEL). Blood flow was evaluated by SPY angiography on day 0 pre- and post-operation, day 21, and day 28. Animals treated with PEP/TISSEEL showed a significant increase in blood flow compared to sham and TISSEEL treated animals (percent perfusion at 28 days: sham 40.9%, TISSEEL 44.3%, PEP/TISSEEL 100.2%), with significant increase in vascular area on histology (at 28 days vascular area (μm 2 )/muscle area(μm 2 ): healthy control 12.71, sham 4.66, TISSEEL 4.76, PEP/TISSEEL 15.54). Conclusions: Exosome driven activation of PI3 kinase can induce angiogenesis both In Vitro and In Vivo. PEP provides a novel, clinical-grade, off-the-shelf therapy to promote angiogenesis for the treatment of peripheral arterial disease.
Abstract 17155: Lipoprotein (a) Testing in an Academic Medical System
Authors: Marwan Hamed, Alborz Sherafati, Lubna Alhalabi, Mohammadreza Naderian, Azin Teymourzadeh, Seyedmohammad Saadatagah, Yakub Nur, Iftikhar J Kullo
Journal: Circulation (2023)

Introduction: Lp(a) is a causal risk factor for ASCVD that is often elevated in patients with personal or family history (FHx) of ASCVD. The 2019 ESC guidelines recommend universal Lp(a) testing, while the 2019 AHA/ACC guidelines include Lp(a) as a ‘risk enhancer’. We used electronic health records (EHR) to assess utilization of Lp(a) testing in patients with ASCVD, premature ASCVD, and FHx of ASCVD at Mayo Clinic sites in Rochester MN, Phoenix AZ and Jacksonville FL and the Mayo Clinic Health System (MCHS) from 1999-2021. Methods: We ascertained Lp(a) testing using LOINC codes and ASCVD status using validated ICD/CPT-based algorithms. ASCVD included coronary heart disease (CHD), cerebrovascular disease (CVD) (ischemic stroke and/or carotid artery stenosis), peripheral artery disease, and abdominal aortic aneurysm. Premature ASCVD was defined as occurring in males &lt; 55 years and females &lt; 65 years. We ascertained FHx using EHR survey data from 2017-2021. We estimated the proportion of patients with ASCVD, premature ASCVD, or FHx of ASCVD who underwent Lp(a) testing. Results: Between 1999-2021, we identified 310,760 patients with at least 1 ASCVD subtype of whom 66,710 had premature disease. FHx data was available starting 2017. For the timeframe 2017-2021, we identified 267,177 patients with FHx of ASCVD and 90,269 ASCVD patients. As summarized in Table 1, Lp(a) was tested only in a small proportion of patients; 7% of ASCVD patients, 11% of premature ASCVD patients, and 6% of patients with FHx of ASCVD. Premature CHD patients had the highest testing proportion (17%). Conclusions: Our results demonstrate underutilization of Lp(a) testing in patients with personal or FHx of ASCVD. Lp(a) is one of the mediators of “ASCVD residual risk” in patients on statins, and with new Lp(a)-lowering medications in phase III clinical trials, patient and provider education will be needed to increase awareness of Lp(a) as a modulator of ASCVD risk.
Abstract 14326: Temporal Trends in Renal Artery Stenting Among Older Patients in the United States
Authors: William B Earle, Siling Li, Yang Song, Anna Krawisz, Jennifer Cluett, Herbert D Aronow, Sahil A Parikh, Brett Carroll, Eric A Secemsky
Journal: Circulation (2023)

Introduction: There is mixed evidence to support renal artery (RA) stenting for improvement in blood pressure control or reduction in cardiovascular and renal events, yet it remains a treatment option in specific clinical scenarios. Contemporary procedural rates and outcomes have been incompletely evaluated. Objective This study aims to describe temporal trends in RA stenting and outcomes among older US patients. Methods: Fee-for-service Medicare beneficiaries age over 65 years, with &gt;1 year of enrollment in Medicare, who underwent RA stenting between January 1, 2016 and December 31, 2020 were included. Outcomes included: (i) a composite of hospitalization for hypertensive urgency, stroke, or myocardial infarction (MI), (ii) new initiation of dialysis, and (iii) need for repeat RA stenting. The cumulative incidence function was used to estimate the incidence of outcomes, accounting for the competing risk of death. Results: A total of 31,359 were included: 55.7% female, average age 75.7 ±6.4 years, 88.9% white and 6.6% black. Among the study sample, 75.9% had chronic kidney disease (CKD), 98.2% had hypertension, and 80.9% had ischemic heart disease. Between 2016-2020, the incidence of RA stenting decreased annually from 27.3 to 15.9 per 100,000 Medicare beneficiaries. The 1-year post-procedure incidence of MI was 4.0%, stroke 2.6%, hypertensive urgency 4.6%, dialysis initiation 2.1% and repeat RA stenting 4.6%. Adverse events occurred more frequently among older patients, Black patients, those whom the indication for RA stenting was cardiovascular disease or CKD, and patients enrolled in both Medicare and Medicaid. ( Fig. 1 ) Conclusion: RA stenting rates in the US are declining, yet it is still frequently used in clinical practice. Post-procedure cardiovascular and renal events are infrequent, but their incidence varies by patient population. Further investigation is warranted to evaluate the risks and benefits of this procedure in specific patient populations.
Abstract 18828: Generation and Characterization of a Novel <i>Myh11</i> Knock-In Smooth Muscle Cell-Specific CreEr <sup>T2</sup> Mouse Model
Authors: Xiangqin He, Kunzhe Dong, Guoqing Hu, David Fulton, Chenleng Cai, Jiliang Zhou
Journal: Circulation (2023)

Background: MYH11 is the most specific and robust marker for differentiated smooth muscle cells (SMCs) and its proximal promoter has been used as a SMC Cre-driver to investigate SMC-specific roles of floxed target genes. Two distinct Myh11-CreER T2 ( Myh11-CreER T2 -Off and -RAD ) mouse lines have been used widely for inducible SMC-specific Cre/loxP-mediated recombination in conditional mutagenesis or lineage tracing. However, both mouse lines were generated using bacterial artificial chromosome (BAC), which were randomly integrated into the genome, potentially resulting in multiple copies of the transgene and the unpredictable disruption of endogenous genes. An additional limitation of the Myh11-CreER T2 -Off mouse is its only works on the male mice. To address these limitations, we generated and characterized a new Myh11-CreER T2 mouse ( Myh11-CreER T2 -KI ), which results from integration of a CreER T2 cassette into the endogenous Myh11 gene locus, enabling faithful SMC-specific lineage tracing or specific gene knockout in SMC in vivo in both sexes. Method: A tamoxifen-inducible, CreER T2 cassette was inserted into one of the Myh11 gene alleles after the initiation codon of Myh11 . To validate the Myh11 CreERT2/+ -mediated gene recombination in SMCs, Myh11-CreER T2 -KI mice were crossed with mTmG dual reporter mice or the lncRNA Carmn GFP knock-in reporter/knockout mice to trace SMC lineages or generate SMC-specific inducible Carmn knockout mice. The recombination specificity in SMCs was analyzed by GFP fluorescence analysis. Results: The CreER T2 cassette inserted into the Myh11 gene locus negligibly affects endogenous MYH11 protein expression. In mTmG / Myh11-CreER T2 -KI reporter mice, GFP expression was detected specifically in both vascular and visceral SMCs in various tissues after tamoxifen mediated Cre activation. Moreover, Myh11-CreER T2 -KI -mediated Carmn SMC-specific deletion in adult female mice recapitulated the lethal intestinal pseudo-obstructive phenotype observed in male Myh11-CreER T2 -Off Carmn KO mice. Conclusions: Our new Myh11-CreER T2 -KI mouse model provides an additional genetic tool using the fidelity of an endogenous SMC gene locus to trace SMC lineages and delete genes in the SMC of both sexes of mice.
Abstract 17206: Targeted Ablation at Regions of High Oxidative Injury in Persistent Atrial Fibrillation in a Canine Model — A New Electrogram Based Therapeutic Strategy in Atrial Fibrillation?
Authors: Markus Rottmann, Anna Pfenniger, Shin Yoo, David Johnson, Wenwei Zhang, Andrew Wasserstrom, Bradley P Knight, Rod S Passman, Rishi Arora
Journal: Circulation (2023)

Introduction: Oxidative stress (OS) plays an important role in the development of atrial fibrillation (AF). However, it is currently not possible to detect regions of high OS in the atria of individual AF patients. Hypothesis: We hypothesized that in persistent AF, electrograms (EGMs) at sites of high OS, are uniquely sensitive to acute reactive oxygen species (ROS) scavenging with N-acetylcysteine (NAC), both in a large animal model and in patients and that ablation at these NAC-sensitive ‘hotspots’ can terminate or slow AF. Methods: We performed high-density mapping (both atria, pre/post-NAC, intravenous, 100mg/kg) in 17 persistent AF dogs (3-14 weeks rapid atrial pacing) using an epicardial mapping-plaque (6 regions, both atria, 130 electrodes, electrode-distance 2.5mm) (Figure 1) and in 5 patients (HD-grid, Abbott). We analyzed cycle length (CL) and dominant frequency (DF) in ‘hot spot’-sub-regions (&gt;10% change pre vs. post-NAC). In 4 dogs we performed epicardial ablation (Atricure) at 3 quadrants of the mapping fields with the largest NAC hotspots of all 6 mapped regions (Figure 2). Results: NAC led to preferential organization of AF (&gt;10% DF decrease) at several sites in both atria (NAC hot spots). In patients, NAC (Figure 3) increased CL in the left atrium in the left lateral wall and in the right atrium in the posterior lateral wall. The largest DF hotspots were in the left atrium in the superior wall. In dogs, ablation at the largest hotspots terminated AF in 50% of the cases (2/4). In all cases, ablation significantly increased CL in the left atrium and decreased DF in all atrial regions (Figure 2). Conclusions: Acute administration of NAC preferentially organizes AF electrograms in subregions of both atria (‘hotspots’). Ablation at these NAC-sensitive hotspot regions terminated or slowed AF. We have discovered a unique method to target identified atrial sub-regions of high OS in the atria. These ‘hotspots’ may be a new therapeutic target in patients with persistent AF.