tbuckley/cabot-search huggingface dataset:
Abstract 13754: Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Alleviate Fibrosis by Reducing Energy Production of Cardiac Fibroblast via Glutamate Metabolism Regulation
Authors: yongjian chen, Jingyi Wang, Cheng Ni, Xin Yang Hu
Journal: Circulation (2023)

Background: Extracellular vesicles derived from bone marrow mesenchymal stem cells (MSC-EVs) have been validated for certain therapeutic effects on cardiac diseases, however, the underlying mechanism and precise bioactive components towards myocardial fibrosis remain unknown. Aim: The current research endeavors to investigate the utilization of MSC-EVs in pressure overload induced fibrosis and unravel the mechanisms of MSC-EVs mediated fibrosis regulation. Methods and Results: Compare to the control group, mice underwent intramyocardial injection of MSC-EVs showed remarkable improvement of cardiac function, as well as cardiac fibrosis post transverse aortic constriction (TAC) surgery. Seahorse XFe Extracellular Flux Analyzer unveiled decreased ATP production in fibroblasts after MSC-EVs administration in vitro . Targeted metabolomics and KEGG pathway analysis revealed glutamate metabolism as the predominantly metabolism process that regulated by MSC-EVs in cardiac fibroblasts. Meanwhile, cell metabolism assays indicated dysregulated α-ketoglutaric level in MSC-EVs treated fibroblasts, which directly lead to an activation of AMPK. Further screening identified glutamic pyruvate transaminase (GPT2) ,which catalyzes glutamic acid to α-ketoglutaric, to be pivotally suppressed by MSC-EVs treatment. Moreover, miR-30c-5p in MSC-EVs was uncovered to inhibit GPT2 expression. In the in vivo TAC model, MSC-EVs pretreated with the miR-30c-5p oligonucleotide did not recapitulated the same results as MSC-EVs do, while MSC-EVs with miR-30c-5p overexpression exerted better therapeutic effect than MSC-EVs alone. Conclusions: MSC-EVs ameliorate cardiac fibrosis via reducing the synthesis of ATP from cardiac fibroblast, which in turn improve cardiac function in mice under pressure overload condition. This effect is mediated by miR-30c-5p in MSC-EVs through the inhibition of GPT2 expression and subsequent AMPK activation in cardiac fibroblasts.
Abstract 137: Importance of Ventilation Rate When Assessing EtCO <sub>2</sub> Levels and Applying TOR Guidelines
Authors: Mikel Leturiondo, Jose Antonio Urigüen, Koldo Redondo, Izaskun Azcarate, Jose Julio Gutiérrez, James K Russell, Mohamud R Daya
Journal: Circulation (2023)

Introduction: Ventilation is essential for the elimination of carbon dioxide (CO 2 ) from the body during CPR. However, variation in ventilation rate (VR) is an acknowledged confounder for the interpretation of EtCO 2 . VRs that are not according to guidelines alter measured EtCO 2 levels and make the decision of termination of resuscitation (TOR) based on EtCO 2 unreliable. Aim: To retrospectively analyze the effect of ventilation rate on levels of EtCO 2 for patients that do not achieve ROSC during prehospital resuscitation. Methods: Capnograms obtained from monitor-defibrillator recordings of non-ROSC adult OHCA cases, attended by TVF&amp;R (OR, USA), were manually inspected to identify individual ventilations. Episodes were partitioned into consecutive 1-min segments, each characterized by its mean EtCO 2 and VR. We corrected the mean EtCO 2 values by adjusting the VRs to the recommended standard for patients with advanced airways (10 vpm), and obtained new EtCO 2,s values multiplying by the standardization factor 1.64 (1 - 0.91 VR ) published previously. Results: One-minute segments ( n = 3,791) from 244 cases were studied, for a total number of 27,312 ventilations. Of these, 206 cases had a duration equal or greater than 20-min, and 9.7% met the TOR criterium of EtCO 2 &lt; 10 mmHg at 20-min. Median (IQR) VR, measured EtCO 2 and corrected EtCO 2,s were 8.1 (6.2-10.6) vpm, 27.7 (17.9-39.8) and 24.1 (16.0-33.7) mmHg, respectively, all at the 20-min mark. Median EtCO 2,s was at all times lower than measured EtCO 2 , with differences from 10 to 20 min ranging from 3.3 to 5.1 mmHg. Conclusion: TOR guidelines lack consensus, but the threshold of EtCO 2 &lt; 10 mmHg at the 20-minute mark of resuscitation, as predictive of non-survivability, needs re-examination. Modern CPR introduces several confounders that produce higher measured EtCO 2 , including low VRs that are common but can be corrected. Based on a ventilation rate of 10 vpm, a new threshold should be considered as part of a multimodal approach in TOR guidelines.
Abstract 14418: Prevalence, Characteristics, and Factors Associated With Atrial Fibrillation and Flutter in Patients With Transthyretin Cardiac Amyloidosis
Authors: Nicholas Chan, Sergio Teruya, Alfonsina Mirabal, Jeffeny De Los Santos, Samantha Guadalupe, Carlos Rodriguez, Stephen Helmke, Margaret Cuomo, Dia Smiley, Angelo B Biviano, Jose Dizon, Elaine Y Wan, Hirad Yarmohammadi, mathew S Maurer
Journal: Circulation (2023)

Introduction: Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized form of restrictive cardiomyopathy in older adults. Adverse chamber remodeling from amyloid infiltration predisposes these patients to tachyarrhythmias such as atrial fibrillation/flutter (AF), which increase the risk of thromboembolic events. The goal of our study was to explore the prevalence, phenotypic characteristics, and factors associated with AF in ATTR-CA patients. Methods: This is a retrospective cohort study of 419 patients diagnosed with ATTR-CA comparing demographics and clinical characteristics between patients with and without AF at baseline. AF was ascertained based on review of prior electrocardiogram, long term monitors when performed, pacemaker interrogations if applicable, and charted history. Binary logistic regression was then performed to determine factors associated with prevalence of AF. Results: AF was prevalent in 58% (n=244) of ATTR-CA patients on initial presentation. Compared to those without AF, individuals with AF were older, of white race, exhibited NYHA class III-IV symptoms, and less frequently had variant disease (ATTRv-CA). They also had more prior stroke/TIA, chronic kidney disease, implanted pacemakers, and need for loop diuretics at baseline (Table 1). AF patients more consistently had Columbia stage II-III disease as per established biomarker cutoffs and greater left atrial volume index on echocardiogram (LAVI). On multivariable logistic regression, per point increase in Columbia score (OR 1.48, 95% CI 1.25-1.75) and per mL/m 2 increase in LAVI (OR 1.05, 95% CI 1.02-1.08) were predictive of prevalent AF, while ATTRv-CA (OR 0.19, 95% CI 0.07-0.55) was protective, all p&lt;0.05. Conclusions: More than half of ATTR-CA patients have preexisting AF. Wild-type ATTR-CA, greater Columbia staging, and a dilated LA are the main clinical factors associated with prevalent AF.
Abstract 16688: Impact on Preoperative Estimation of Atrial Mechanical Amplitudes Before With VDD Leadless Pacemaker
Authors: Yuya Komai, Yusuke Kondo, Masahiro Nakano, Takatsugu Kajiyama, Ito Ryo, Toshinori Chiba, SATOKO RYUZAKI, Yutaka Yoshino, Yukiko Takanashi, Yoshio Kobayashi
Journal: Circulation (2023)

Introduction: It would be useful to judge whether the device can sense atrial systole or not before an implantation of a VDD leadless pacemaker (Micra AV RT , Medtronic, US). Hypothesis: Mechanical atrial amplitude for Micra AV RT associated with atrial construction at implantation location. Methods: Echocardiographic measurements were performed to quantify the atrial motion of the interventricular septum in patients who received leadless pacemaker implantation. We visually divided the septum into five segments from the base to the apex. The myocardial velocity of each segment measured on tissue doppler imaging (TDI) was defined as EV1, 2, 3, 4, and EV5 (m/s), respectively. Results: Fourteen patients (79.5 years, 8 males) receiving Micra AV from November 2021 to February 2023 at our institution were analyzed. The average myocardial velocity of atrial contraction at each site tended to decrease as getting closer to apex (EV1:8.9, EV2:8.0, EV3:7.0, EV4:5.8, EV5:3.5 cm/s) as shown in Figure. The implantation location was estimated from fluoroscopy and postoperative echocardiography, and mechanical atrial amplitude (A4) and the local EV were compared; Patients with lower than 2.0 m/s 2 A4 had also lower the local EV than others. (3.6 vs 5.9 m/s, p=0.037). Conclusions: Preprocedural estimation of mechanical atrial amplitude of Micra AV is possible on septal TDI.
Abstract 13778: Effects of Omega-3 Fatty Acid Supplementation on Revascularization and Major Cardiovascular Events: A Systematic Review and Meta-Analysis
Authors: Francesco Sofi, Monica Dinu, Sofia Lotti, Luca Genovese, Anna Vittor Mattioli, Giuseppe Ambrosio
Journal: Circulation (2023)

Background: Benefits of omega-3 administration in preventing cardiovascular (CV) events are controversial. In particular, while statins have been associated with significant reduction of revascularizations (Revasc), effects of omega-3 on Revasc are unclear. Aim: To metanalyze evidence on the effect of omega-3 administration on incident Revasc and CV events (myocardial infarction [MI], stroke, heart failure [HF], CV death). Methods: We searched MEDLINE, Embase, Scopus, Web-of-Science and Cochrane Library for randomized controlled trials (RCTs) with ≥500 participants comparing the effects of omega-3 formulations [decosahexanoic acid+eicosapentaenoic acid (DHA+EPA) or EPA alone] versus placebo. Results: Seventeen RCTs with participants (both primary and secondary CV prevention) randomized to DHA+EPA (n=52,498) or EPA alone (n=13,415) and controls (n=65,771) were included. Follow-up ranged from 4.5 months to 7.4 years. Significant heterogeneity emerged among studies (Figure). Overall, compared to controls omega-3 supplementation was associated with reduced risk of Revasc (Figure) and MI [0.89, 95% CI 0.80-0.98; p heter =0.04; I 2 =45%; p=0.02] with no significant effect on stroke, HF, and CV death. Reduced risk of Revasc was still observed when most (≥60%) participants were already on statins (Figure). Compared to DHA+EPA, EPA alone was associated with a greater reduced risk of Revasc (Figure) and stroke [0.72, 95% CI 0.55-0.95], with no significant effect on HF and CV death. No significant differences were observed for DHA+EPA dose ≤0.9g/day vs &gt;0.9g/day, or EPA alone ≤0.7 g/day vs &gt;0.7 g/day. Conclusions: Omega-3 supplementation resulted in reduced risk of Revascularization, unaffected by background statin use. Use of EPA alone appeared to be associated with even greater benefits. Further studies are needed to clarify the role of omega-3 supplementation in preventing hard CV events
Abstract 17680: MIBG Myocardial Scintigraphy is Useful for Predicting CTRCD Caused by Trastuzumab
Authors: Takahisa Noma, Atsushi Tobiume, keigo kawaguchi, seiji moriya, Yu Ishihara, Minako Ohara, Makoto Ishizawa, KAORI ISHIKAWA, Kazushi Murakami, Tetsuo Minamino
Journal: Circulation (2023)

Introduction: Trastuzumab is known to reduce the mortality rate, recurrence rate, and metastasis rate in Human epidermal growth factor receptor type 2 (HER2)-positive breast cancer patients, and it is recommended to administer it for 12 months to all early-stage HER2-positive breast cancer patients. However, trastuzumab administration can lead to Cancer Therapeutics-Related Cardiac Dysfunction (CTRCD). The guidelines suggest that regular echocardiography every 3 months is useful for early detection of CTRCD, but there are no tests available to predict it before its onset.The purpose of this study is to determine whether cardiac sympathetic nerve evaluation using MIBG myocardial scintigraphy before trastuzumab administration can predict the development of CTRCD three months after administration. Methods: MIBG myocardial scintigraphy was performed before trastuzumab administration in 35 HER2-positive breast cancer patients, and cardiac function assessment was conducted using echocardiography before administration, at 1 month, and at 3 months. Simultaneously, NT-proBNP and troponin levels were measured. CTRCD was defined as a decrease in global longitudinal strain (GLS) of 10% or more from before administration at the 3-month follow-up. Results: Anthracycline and trastuzumab regimens were used in 21 patients (60%). CTRCD occurred in 17 patients at the 3-month follow-up. There were no significant differences in age or previous medication between the CTRCD group and the non-CTRCD group, but the early H/M ratio in MIBG myocardial scintigraphy was significantly lower in the CTRCD group (2.77±0.36) compared to the non-CTRCD group (3.10±0.36) (p&lt;0.01). There were no significant differences in the delay H/M ratio or washout rate. None of the echocardiographic parameters, NT-proBNP levels, or troponin levels showed significant differences and did not become predictive factors. Conclusions: MIBG myocardial scintigraphy is useful for predicting CTRCD caused by trastuzumab. Preclinical studies have suggested that HER2 transactivation from β-adrenergic receptors in the myocardium confers cardioprotection. Suppression of HER2 signaling during cardiac sympathetic nerve dysfunction potentially contributes to the development of CTRCD.
Abstract 14472: Identifying the Genetic Determinants of Early Heart Failure in Patients With Congenital Heart Disease
Authors: Courtney A Bair, Leonie Kurzlechner, Ian George, Gabrielle Monaco, Amy Berkman, Judah Kreinbrook, Mary E Moya-Mendez, carla dominguez Gonzalez, Manasa Gurumoorthi, MINU BIDZIMOU, Leslie Pace, Andrew Allen, Ziv Beckerman, Nicholas D Andersen, Joseph W Turek, Martha Elisabeth Leong, Timothy Hoffman, Jennifer S Li, Andrew P Landstrom
Journal: Circulation (2023)

Introduction: Heart failure (HF) is the most common cause of death in patients with congenital heart disease (CHD). Evidence suggests genetics play a role in HF predisposition. In particular, variants in cardiomyopathy-associated genes may be associated with HF and early mortality in CHD populations. Goal: Our goal is to leverage a large, well-curated, population-based cohort of individuals with CHD in North Carolina (NC) to determine the genetic underpinnings of HF in CHD. Hypothesis: We hypothesize that rare variants in cardiomyopathy-associated genes will be over-represented in CHD patients with HF compared to patients without HF. Methods: Patients were enrolled with inclusion criteria of 1) presence of CHD, 2) 2+ cardiac evaluations. Whole blood was collected for exome sequencing (ES). The presence of HF was defined as death, cardiac transplantation or listed for cardiac transplantation, VAD placement, ECMO cannulation, EF ≤ 40% on 2 images, or diagnosis of HF by a cardiologist and taking at least 1 HF medication. ES data was filtered for variants in cardiomyopathy-associated genes. Results: We have established NC-DEFINE: Determining the Genetic Basis of Heart Failure in Patients with CHD in NC, a prospectively enrolled cohort of patients with CHD for which ES data are available. We enrolled 138 CHD patients (mean age at enrollment [std dev]: 7.44+/-11.89 years; 40.6% female, 1.4% Asian, 23.9% Black, 6.5% Hispanic). About half (52.9%) have single ventricle physiology and 26% have HF. In a pilot ES cohort of 48 patients, there was an average of 524.2 variants/patient in cardiomyopathy genes of interest. After filtering out common and tolerated variants, 8 loss-of-function and 28 missense variants were identified and interpreted using ACMG criteria. Likely pathogenic or pathogenic (LPP) variants were found in 26.9% (7/26) of HF patients and 9.1% (2/22) of non-HF patients ( p =0.15). The RR for having a cardiomyopathy-associated LPP variant and developing HF in the setting of CHD was 1.60 (95% CI 1.0-2.57). Conclusions: We have established NC-DEFINE, a novel prospectively enrolled CHD cohort, to define the genetic architecture of HF in CHD. In a pilot ES cohort, we found enrichment of rare, LPP variants in cardiomyopathy-associated genes in patients with HF.
Abstract 12489: Sex Differences in Incidence and Outcomes of Patients With New-Onset Post-Transplant Diabetes Mellitus After Heart Transplantation
Authors: Alice Chung, Heidi Hartman, Stephanie Golob, Daniella Concha, Jaya Batra, Ersilia DeFilippis, Gabriel T Sayer, Farhana Latif, Melana Yuzefpolskaya, Jayant Raikhelkar, Justin A Fried, Koji Takeda, Nir Uriel, Kevin Clerkin
Journal: Circulation (2023)

Introduction: Post-transplant diabetes mellitus (PTDM) is a common complication following heart transplantation (HT), mostly commonly occurring in the first year after transplant. A few risk factors for the development of PTDM have been identified, including immunosuppressive medications such as calcineurin inhibitors and glucocorticoids. Some studies have suggested that among HT recipients, women have higher rates of acute rejection which may necessitate higher doses of steroids and further hyperglycemia. However, differences between sexes in the incidence of PTDM after HT have not been established. Methods: A retrospective review of patients who underwent HT at a large-volume center between January 1, 2010 and December 31, 2019 was performed. Patients undergoing re-transplantation or dual-organ transplantation were excluded. PTDM was defined as hemoglobin A1C≥6.5% or a random glucose &gt;200 after HT among patients with no prior history of DM. Predictors of PTDM by sex were analyzed with logistic regression, and post-transplant outcomes were analyzed with Chi-Square analysis. Results: Among 317 transplant patients without pre-transplant DM, 71 (22.4%) patients were identified who had PTDM: 24 females (33.7%), 47 males (66.2%). There were no statistically significant differences in baseline characteristics between males and females who developed PTDM including age, race, pre-transplant HTN, calcineurin or steroid dosing at 1 month and 1 year post-transplant. Baseline HTN (OR 2.9, [1.3, 6.7], p=0.009) and mean steroid dose over the first 2 years post-transplant (OR 1.2, [1.0, 1.3], p=0.006) were predictors of PTDM in females but not in males, and mean tacrolimus dose was a predictor in males (OR 1.1, [1.0, 1.2], p=0.001) but not in females. Time to PTDM diagnosis did not differ by sex (log-rank p=0.56). Additionally, post-transplant outcomes in patients with PTDM including acute cellular rejection, antibody-mediated rejection, coronary allograft vasculopathy and death did not differ by sex. Conclusion: PTDM is a common complication of HT. Our study suggests that risk factors for PTDM among HT recipients differ by sex. Future studies should investigate the mechanisms underlying these differences to further guide sex-specific post-HT care.
Abstract 16620: Long-Term Prognostic Factors for Cardiovascular Events in Patients With Chest Pain Without Diabetes Mellitus and Significant Coronary Stenosis
Authors: Seung-Woon Rha, Byoung Geol Choi, Woo Jin Ahn, Se Yeon Choi, Jae Kyeong Byun, Jinah Cha, Sujin Hyun, Soohyung Park, Dong Oh Kang, Eun Jin Park, Cheol Ung Choi
Journal: Circulation (2023)

Background: Chest pain is the most common symptom of coronary artery disease (CAD) and diabetes mellitus (DM) is a well-known single strongest risk factor for cardiovascular diseases. Thus, the impact of CAD and DM on long-term clinical effects is reported widely, but the prognostic factors of non-DM patients presenting with chest pain without significant CAD are limited. Methods: A total of 1,046 patients with chest pain without DM and significant CAD who underwent coronary angiography (CAG) and acetylcholine (ACH) provocation tests were finally enrolled. Propensity score matching and multivariate Cox-proportional hazard ratio analysis were performed to adjust for baseline potential confounders. Major adverse cardiovascular events (MACE) were defined as the composite of total death, myocardial infarction (MI), and revascularization. Major adverse cardiac and cerebrovascular events (MACCE) were defined as the composite of MACE, stroke, and recurrent angina. This study aimed to evaluate the long-term prognostic factors for MACCE in patients with chest pain without DM and CAD up to 5 years. Results: Coronary artery spasm (CAS) was the most common cause of chest pain. However, long-term MACCE of CAS was not worse than those of patients with chest pain without CAS when patients with CAS had subsequent optimal anti-anginal medication therapy. However, a recurrent chest pain remains a problem even with continuous anti-anginal medication therapy. Up to 5-year, the incidence of MACCE was in 7.3%, including recurrent angina 6.9%. Dyslipidemia, ICS, the use of aspirin and nitrates were associated with long-term MACCE. Conclusions: Among the patients with chest pain without DM and significant CAD, the incidence of MACE were rare, but recurrent angina was still a challenging problem who had treated with anti-anginal medications.
Abstract 18079: Forecasting Inpatient Cardiology Consultation and Transthoracic Echocardiogram Volumes
Authors: Catherine Wang, Matthew C Tattersall, Hessam Bavafa, Bob Batt, Matthew M Kalscheur
Journal: Circulation (2023)

Introduction: The demand for inpatient cardiology consultation and transthoracic echocardiography (TTE) places a significant strain on hospital resources. There is limited understanding of the frequency and predictors of cardiology consultations and TTE in a real-world inpatient setting which hinders efforts to optimize staffing and workload expectations. Forecasting methods may shed light on these critical aspects of healthcare delivery. Hypothesis: Forecasting methods may predict the daily volumes of inpatient cardiology consultations and TTEs in an academic medical center. Methods: Our study examines the daily consultation and TTE ordering patterns using a dataset of over 26000 adult patients admitted to a teaching hospital in 2019 under “observation” or “inpatient” status. Using individual patient characteristics and clinical data, we sought to forecast the probability of a cardiology consult or TTE being ordered at the patient level and then aggregated these probabilities to predict daily volumes. The dataset was partitioned into a training cohort (80%) and a testing cohort (20%). Models tested included logistic regression, random forest, support vector machine, neural networks, gradient boosting machines, and hybrid models. Model performance was assessed using mean absolute error (MAE). Results: In 2019, the average daily cardiology consult and TTE volumes were 2.8 (SD = 1.5) and 13 (SD = 4.5), respectively, in the hospital studied. No strong seasonal pattern was observed in the consultation and TTE orders. Utilizing individual-level forecasting followed by aggregation at a daily level resulted in reasonable daily estimates. Preliminary results indicate that the best-performing machine learning-based models for individual predictions yield MAE values ranging from 1.06 to 1.19 for consultations and from 3.18 to 3.62 for TTEs. These findings suggest that, on average, the predictions deviate by approximately 1 unit in absolute value for consultations and around 3 units in absolute value for TTEs from the true values. Conclusion: Our findings suggest the feasibility of utilizing machine learning models for individual predictions to forecast and facilitate planning for hospital inpatient cardiology consultations and TTE volumes.