tbuckley/cabot-search huggingface dataset:
Abstract 4143935: Clinical and Hemodynamic Correlates of Supranormal Ejection Fraction in Heart Failure with Preserved Ejection Fraction (HFpEF)
Authors: Ritika Dhruve, Lajjaben Patel, Vinayak Subramanian, Matthew Segar, James Miller, Nidhish Lokesh, Neil Keshvani, Dan Tong, Alvin Chandra, Thomas Koshy, Ambarish Pandey
Journal: Circulation (2024)

Introduction: Patients with heart failure with preserved ejection fraction (HFpEF) with EF≥65% may have a higher risk for adverse outcomes, however, the exercise, functional status, and hemodynamic correlates of this phenotype in a contemporary cohort is not well defined. Methods: This single-center study included patients with LVEF ≥50% with clinically indicated invasive right heart catheterization and echocardiogram enrolled in a prospective HFpEF registry at UT Southwestern between 4/2022-5/2024. Participants underwent peak oxygen uptake (VO 2 ) assessment with maximal bicycle test (Lode ergometer), quality of life assessment (Kansas City Cardiomyopathy Questionnaire [KCCQ]), physical function testing with the Short Physical Performance Battery (SPPB), and 6-minute walk distance (6MWD). Participants were stratified by those with EF ≥ 65% and EF 50%-65%. Multivariable adjusted linear regression models were used to evaluate the association of EF ≥ 65% with peak VO 2 , quality of life, noninvasive and invasive cardiac filling pressures, and functional outcomes. Results: 347 participants were included in the study. 112 (32.3%) participants had EF≥65%, and there were no differences in demographics across EF subgroups. Patients with EF≥65% had a higher burden of hypertension (94.6% vs. 86.8%, p = 0.04) and had higher E/e’ (14.0[95% CI 10.9-18.0] vs. 12.7[95% CI 9.5-16.7], p = 0.048) and PCWP with exercise (27[95% CI 20-30] vs 22[95% CI 18-28] mmHg, p=0.04) without differences in resting PCWP or PCWP/cardiac output slope at maximal exercise. After adjustment for age, sex, race, and BMI, EF≥65% was associated with higher KCCQ. However, these findings were attenuated after adjustment for comorbidities (Model 1: β 6.6, p=0.05 vs Model 2: β 6.0, p=0.08). EF≥65% was not associated with functional outcomes, peak exercise capacity, or elevated filling pressures in adjusted models. (Table) Conclusions: There were no significant differences in quality of life, functional status, exercise capacity, and filling pressures among patients with supranormal and normal ejection fraction. These findings suggest that extra-cardiac mechanisms may be more important contributors to functional status and peak exercise capacity in patients with EF≥65%.
Abstract 4143844: Multidisciplinary management of a pregnant patient with advanced systolic heart failure
Authors: Jameson Mitchell, Karlee Hoffman, Katherine Singh
Journal: Circulation (2024)

A 35-year-old gravida 1, para 0 with biventricular heart failure (LVEF 25%), nonischemic cardiomyopathy, history stroke, history of left ventricular thrombus, class III obesity, and chronic kidney disease who had been followed by Cardio-Obstetrics throughout her pregnancy presented at 34 weeks gestation for planned induction of labor. Upon presentation, she underwent assessment with a pulmonary artery catheter (PAC) and was noted to be in cardiogenic shock with elevated biventricular filling pressures and low cardiac index necessitating hemodynamic stabilization followed by primary cesarean section. The patient was admitted to the cardiac ICU for medical optimization prior to delivery. Home medications including isosorbide dinitrate, metoprolol, and hydralazine were continued. The patient was briefly placed on inotropic support with dobutamine, which was discontinued due to ectopy. After PAC-guided IV diuresis, anticoagulation transition from enoxaparin to heparin, and twice daily fetal monitoring via non-stress test, a multidisciplinary team, including cardiology, maternal fetal medicine, cardiac anesthesia, and cardiothoracic surgery assembled for the C-section. Following pre-delivery cannulation for potential ECMO support, the patient underwent C-section and elective salpingectomy under epidural anesthesia with delivery of a healthy neonate. Post-delivery, the patient was monitored in the ICU, focusing on fluid management, anticoagulation transition to warfarin, and titration of heart failure medications, as the patient did not plan to breastfeed. After discharge, she was scheduled for a 2-week postpartum visit including echocardiogram, EKG, and NT-proBNP. Discussion: Given the patient's acute decompensation and fluid overload, medical optimization was essential prior to delivery. However, stabilization was expected to be temporary due to ongoing physiologic changes of pregnancy. Her limited mobility and concern for multiorgan compromise, such as new oxygen dependency and rising creatinine, made a prolonged induction of labor unfeasible. Due to concern for maternal intolerance of labor, unstable fetal lie, fetal distress due to decreased perfusion, and an increased likelihood of emergency C-section, a primary C-section was recommended as a safer option. The successful delivery of a healthy neonate and post-operative maternal stabilization highlights the importance of a multidisciplinary approach in managing complex cardio-obstetric cases.
Abstract 4143897: Monocyte regulation of magnesium during salt sensitivity of blood pressure
Authors: Ashley Mutchler, Mert Demirci, Annet Kirabo
Journal: Circulation (2024)

Background: Dietary magnesium (Mg +2 ) deficiency has been linked to hypertension, chronic kidney disease, and cardiovascular disease. High sodium intake and reduced dietary Mg +2 consumption are associated with elevated blood pressure. We have previously shown a role for monocyte-producing isolevuglandins (IsoLGs) in the pathogenesis of salt-sensitivity of blood pressure (SSBP) and, in a separate study, dietary Mg +2 deficiency. However, it is unknown whether decreased Mg +2 contributes to IsoLG-adduct formation in SSBP[DM1] [PA2] . We hypothesized that decreased Mg +2 transport into monocytes leads to IsoLG-adduct formation during SSBP. Methods: In vitro studies were performed on isolated monocytes from 11 healthy patients treated with normal salt (150mM) and high salt (190mM) and submitted for RNAseq. In vivo studies were performed on 9 hypertensive subjects enrolled in an acute inpatient protocol of salt loading (SL) (460mmoL/24 hrs) and salt depletion (SD) (10mmoL/24 hrs, and furosemide 40mg x 3). Isolated PBMCs were analyzed using CITE-seq (cellular indexing of transcriptomes and epitopes). IsoLG-containing classical monocytes were identified using flow cytometry. Pearson correlation was used to analyze the associations. Salt sensitivity index (SSI) is the difference in SL versus SD systolic blood pressure. Results: Using an unbiased approach, I utilized the Harmonizome 3.0 database to identify genes involved in Mg +2 homeostasis. I identified 75 genes and cross-referenced them with our bulk RNAseq data. Analysis of differentially expressed genes demonstrated a downregulation in Mg +2 transporter 1 (log2FC=-0.44, p-adj=0.01) and cyclin M2 ( CNNM2 ) (log2FC=-0.34, p-adj=0.006) with an upregulation of solute carrier family 41 member 1 (log2FC=0.39, p-adj=0.006) in response to high salt media. In our inpatient cohort, baseline monocyte expression of CNNM2 negatively correlated with SSI (r=-0.72; p=0.045). There was a positive correlation between baseline CNNM2 with baseline %IsoLG+ classical monocytes, although not statistically significant (r= 0.69; p=0.06). Similarly, there was a trend of negative correlation of baseline %IsoLG+ classical monocytes with increasing SSI, though not significant (r=-0.68; p=0.06). Conclusions: Our preliminary findings suggest high salt downregulates Mg +2 transporters and decreased Mg +2 transport are potentially associated with monocyte-derived IsoLG-adduct formation, thus exacerbating the inflammatory response in SSBP.
Abstract 4143983: Benefits and Risks Associated with Mineralocorticoid Receptor Antagonists in Tafamidis-treated Transthyretin Amyloid Cardiomyopathy: A Real-World Analysis
Authors: Kuan Yu Chi, Pawel Borkowski, Anita Osabutey, Dimitrios Varrias, Junmin Song, Yu Chang, Shivank Madan, Snehal Patel
Journal: Circulation (2024)

Background: There is currently no data on the use of mineralocorticoid receptor antagonists (MRA) in tafamidis-treated transthyretin amyloid cardiomyopathy (ATTR-CM). Research Question: Does the addition of MRA provide extra benefits in ATTR-CM patients treated with tafamidis? Aim: To assess the benefits and risks associated with MRA in tafamidis-treated ATTR-CM through a new-user design propensity-score matching (PSM) analysis. Methods: We conducted a retrospective, PSM cohort study using the TriNetX Global database. We included adult ATTR-CM patients who had their first tafamidis prescription within 1 year after the identification of amyloidosis between January 1, 2018, and May 1, 2023. MRA users and non-users were subsequently identified, with the former defined as those having both tafamidis and spironolactone/eplerenone, and the latter having tafamidis without MRA. Patients with prior MRA use before their first tafamidis prescription were excluded. The primary endpoint was major adverse cardiac events (MACE), defined as a composite of all-cause mortality, heart failure (HF) hospitalization, or cardiac arrest/ventricular tachycardia/fibrillation. Secondary endpoints were individual MACE. The safety endpoint was a composite of acute kidney injury (AKI) or hyperkalemia. Incident gastrointestinal bleeding and pneumonia were set as falsification endpoints. We compare study endpoints occurring within two years of tafamidis initiation between MRA users and non-users. Results: Among 2,174 tafamidis-treated ATTR-CM patients, 471 MRA users were matched to 471 non-users with similar age (76.7 vs. 76.7), sex (female, 16.8% vs. 17.4%), and mean ejection fraction (50.1% vs. 49.9%). Amyloid staging markers and important medications were also balanced (Figure) . MRA use was not associated with a significant reduction in MACE (HR, 0.90; 95% CI, 0.64 to 1.27) (Figure) . Conversely, it was associated with a significant increase in AKI or hyperkalemia (HR, 1.69; 95% CI, 1.13 to 2.54) (Figure) . The two falsification endpoints were comparable between the two groups (Figure) . Conclusions: In ATTR-CM patients treated with tafamidis, MRA was not associated with a significant reduction in MACE but with an increased risk of AKI or hyperkalemia.
Abstract 4143923: Home-based Exercise Intervention for Children and Adolescents with Hypertrophic Cardiomyopathy: A Consensus of Experts on a Safe and Acceptable Exercise Protocol
Authors: Charles-Olivier Fortin-Moore, Aamir Jeewa, Alyssa Power, Michael Khoury, Kimberly Lin, Jonathan Edelson, Geoff Ball, Joseph Atallah, Barbara Cifra, Tara Pidborochynski, Jennifer Conway
Journal: Circulation (2024)

Background: Physical activity (PA) is a mainstay for cardiovascular health. However, those with hypertrophic cardiomyopathy (HCM) are often counselled to limit PA due to the potential risk of sudden cardiac death. The emphasis placed on restriction has put this population more susceptible for acquired cardiovascular (CV) risk factors, and poor long-term CV health from physical inactivity. To date, no consensus exists about what is appropriate and safe in terms of exercise for this population. Project Aim: Use a modified Delphi method to gain consensus amongst subject matter experts on a proposed home-based exercise intervention for children 10 to 19 years of age with HCM. Methods: A panel of experts, including pediatric cardiologists, sports cardiologists, exercise physiolologists, obesity experts, and parent/patient representatives met a series of five times to develop a home-based exericse program. The proposed program was converted into a survey and sent out through the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) from October 2023 to June 2024. Utilizing a modified Delphi method, each of the 11 components of the intervention were voted on regarding the degree of agreement by responders. For those who disagreed, they were prompted to provide feedback in order to modify that aspect of the exercise program. The participants were provided with feedback after each round. We aimed for 90% agreement on each component to declare consensus. Results: At total of 49 individuals completed the first round of the survey with 84% identified as a pediatric cardiologists, 75% working in a University center and two-thirds having more than five years of experience. After Round 1 consensus was reached on 3/11 and up to 8/11 after Round 2. The progression to the final home-based exercise protocol is outlined in Table 1. Conclusion: A home-based exercise program for children with HCM was developed, adapted from feedback, and the components were agreed to by experts in the field using a modified Delphi method. The next step in this process is to assess the safety and feasibility of this program in an in-hospital setting, prior to its evaluation through a multi-center, home-based exercise intervention.
Abstract 4143977: Cardiovascular Toxicities in Chimeric Antigen Receptor Therapy in Relapsed and Refractory Multiple Myeloma and Lymphoma using FAERS database.
Authors: Fathima Shehnaz Ayoobkhan, Tarun Parvataneni, Suryakumar Balasubramanian, Mohammad Arfat Ganiyani, Matta Temujin Reddy
Journal: Circulation (2024)

Introduction: Chimeric Antigen Receptor T-cell therapy (CAR-T) has revolutionized the treatment of relapsed refractory multiple myeloma (RRMM) and lymphoma over the past decade. Our objective is to examine the incidence, patterns, and outcomes of cardiac events in patients with RRMM and lymphoma who are receiving CAR-T therapy, utilizing the FDA Adverse Event Reporting System (FAERS) database. Methods: We employed the FDA Adverse Event Reporting System (FAERS) database and the Medical Dictionary for Regulatory Activities (MEDRA) to conduct a retrospective post-marketing pharmacovigilance inquiry. We analyzed the incidence of cardiac events associated with six CAR-T products, namely Idecabtagene vicleucel, Cilitacabtagene autoleucel, Axicabtagene ciloleucel, Tisagenlecleucel, Lisocabtagene maraleucel, and Brexucabtagene autoleucel, since their FDA approval (accessed 05/01/2024). We assessed the cardiotoxicities such as coronary artery disease (CAD), myocardial infarction (MI), arrhythmia, heart failure, and hypotension. Results: A total of 12,949 adverse events, including Axicabtagene ciloleucel (n=6222, 48%), Brexucabtagene autoleucel (n=1127, 8.7%), Tisagenlecleucel (n=3290, 25.4%), Lisocabtagene maraleucel (n=463, 3.5%), Idecabtagene vicleucel (n=722, 5.5%), and Cilitacabtagene autoleucel (n=1125, 8.6%). Of those, 675 cases (5.2% of the total) that were related to cardiac events, regardless of their severity. The cardiotoxicity incidence was highest in Brexucabtagene autoleucel (n=85,7.5%), followed by Idecabtagene vicleucel (n=50,6.9%), Tisagenlecleucel (n=208,6.3%), Axicabtagene ciloleucel (n=278,4.5%), Lisocabtagene maraleucel (n=17,3.6%), and Ciltacabtagene autoleucel (n=37,3.2%). Cytokine release syndrome (CRS) is linked to nearly 440 cardiac events,accounting for 65% of all cardiac events. The most prevalent cardiotoxic event was Atrial Fibrillation (122), followed by the development of heart failure (113), Ventricular arrhythmia (108), hypotension (87), and Brady arrhythmia (41). The recipients of Brexucabtagene autoleucel had the highest mortality rate (n = 26,2.3%), followed by those receiving Tisagenlecleucel (n = 71,2.1%) and Lisocabtagene maraleucel (n = 10,2.1%). Conclusion: The cardiotoxic properties of CAR-T therapy can lead to fatal adverse events. Improving outcomes and preventing mortality in these populations can be achieved through timely monitoring.
Abstract 4143858: Does Cognition Effect the Outcomes of Two Types of Virtual Cognitive Behavioral Therapy Interventions to Improve Depressive Symptoms in Patients with Cardiovascular Disease?
Authors: Jessica Thompson, Jia-Rong Wu, Misook Chung, Geunyeong Cha, Abigail Latimer, Chin-Yen Lin, JungHee Kang, Martha Biddle, Debra Moser
Journal: Circulation (2024)

Background: Depressive symptoms are prevalent in patients with coronary heart disease (CHD) and heart failure (HF) living in rural areas and are associated with worse health outcomes. Cognitive behavioral therapy (CBT) has been shown to be effective at improving depressive symptoms in patients with CHD and HF. Traditional CBT is not accessible to many rural individuals, thus alternative virtual modalities are being tested to ascertain their effectiveness. Cognitive impairment is a core feature of depressive disorders and is prevalent in up to 95% of all clinical depression diagnoses. It is unknown how cognition impacts the reduction of depressive symptoms in patients utilizing virtual CBT interventions. Aim: To determine if cognition moderates the impact of two different modalities of virtual CBT on depressive symptoms over a 12-month period. Methods: This is an on-going 12-month randomized comparative effectiveness trial. Participants with at least mild depressive symptoms were randomly assigned to CBT with either a video-conference with a therapist or a self-directed internet-based application. Depressive symptoms were measured by the Patient Health Questionnaire-9 (PHQ9) and were measured at baseline, 3-, 6-, and 12-months. Cognition was measured at baseline using two instruments, the MOCA and the Mini-Cog. Those with significant cognitive dysfunction were excluded from the study. Scores were standardized from both instruments using Z-scores and separated by the median into lower cognitive function and higher cognitive function. Repeated measures ANOVA was performed to determine whether cognitive function interacted with either intervention to produce an effect on depressive symptoms over time. Results: Participants (n=305) were 58±12 years old, 49% female, and had 13±3 years of education. Baseline PHQ-9 scores showed no significant difference between lower and higher cognition groups. (12±6 vs 11±5, respectively, p=.17). There was no interaction of cognition by intervention group on depressive symptoms (p=0.217). Both intervention groups had significant decreases in depressive symptoms over time (p&lt;0.001 for time effect). There was no between-group difference in improvement of depressive symptoms (p=0.059). Conclusion: Both cognitive groups experience significant symptom reduction with virtual CBT, suggesting effectiveness regardless of cognitive function in rural CHD and HF patients, provided significant cognitive dysfunction is absent.
Abstract 4143974: hiPSCs Derived Cardiomyocyte Spheroid Transplantation Induces Proliferation of Pig Myocytes by Mediating YAP Signaling
Authors: Yuhua Wei, Gregory Walcott, THANH NGUYEN, Xiaoxiao Geng, Bijay Guragain, Hanyu Zhang, Akazha Green, Manuel Rosa-Garrido, Jack Rogers, Daniel Garry, Lei Ye, Jianyi Zhang
Journal: Circulation (2024)

Background: Our previous study showed that cardiomyocytes (CMs) differentiated from hiPSCs with cyclin-D2 overexpression ( CCND2-OE hiPSC-CMs) induced the proliferation to repopulate &gt; 50% of the scar in immunodeficient mouse hearts. To reduce the immunogenicity of CCND2-OE hiPSCs, we knocked out the HLA classes -I and -II ( KO/OE hiPSCs) and assessed the therapeutic efficacy and mechanism of KO/OE hiPSCs-derived CMs ( KO/OE hiPSC-CMs) for myocardial infarction (MI) treatment. Methods: KO/OE hiPSC-CM or wild-type hiPSC-CM ( WT hiPSC-CM) spheroids were differentiated in shaking flasks, purified, characterized, and injected into pig hearts post ischemia/reperfusion (I/R), while controls received medium injection only. Cardiac function was evaluated using cardiac magnetic resonance imaging (cMRI). CM proliferation was assessed through immunostaining and single-nucleus RNA sequencing (snRNAseq). Results: KO/OE hiPSC-CM spheroids secreted abundant follistatin compared to WT hiPSC-CM spheroids (30.3±4.13 vs 16.6±1.43 ng/mL, p=0.0056). Follistatin, which interacts with HIPPO/YAP pathway, stimulated WT hiPSC-CM proliferation and increased cell number by 28.3% over 16 days in vitro and promoted adult mice CM proliferation after MI in vivo . cMRI assessments indicated better cardiac function and scar sizes in KO/OE hiPSC-CM spheroid treated pig hearts compared to medium or WT hiPSC-CM spheroid treated pigs. Although the injected cells were only identified at 1 week, cell-cycle activity was significantly higher in the CMs of KO/OE hiPSC-CM spheroid treated pig hearts compared to the other two groups. A cluster of cycling CMs, enriched for five genes associated with cell proliferation according to snRNAseq data, was more prevalent in the KO/OE hiPSC-CM spheroid (3.65%) compared to the medium (0.89%) or WT hiPSC-CM spheroid treated (1.33%) hearts at 1 week. Pathways linked to cardiac regeneration—MAPK, HIPPO/YAP, and TGFB—were significantly upregulated in pig CMs treated with KO/OE hiPSC-CM spheroids. Furthermore, YAP protein levels and nuclear localization in CMs were higher in the KO/OE hiPSC-CM spheroid treated pig hearts compared to controls. Thus, follistatin secreted by implanted KO/OE hiPSC-CM spheroids appear to target the HIPPO/YAP pathway to promote pig CM proliferation. Conclusions: KO/OE hiPSC-CM spheroids significantly improved cardiac function and reduced infarct size in pig hearts after I/R by secreting follistatin which promoted pig CM proliferation through YAP signaling.
Abstract 4143931: Guideline Adherence in Severe Aortic Stenosis: Determinants of Timely Aortic Valve Replacement and Echocardiography Follow-up
Authors: Azin Vakilpour, Michael Levin, Emeka Anyanwu, Srinivas Denduluri, Jennifer Lee, Tiffany Sharkoski, Srinath Adusumalli, Juan Lopez-Mattei, Jesse Chittams, David Jones, Kathleen Weiss, carlton hartwell, Michael Bolooki, Jamieson Bourque, Marielle Scherrer-Crosbie
Journal: Circulation (2024)

Background: According to the 2020 ACC/AHA guidelines, patients with severe aortic stenosis (AS) should either undergo rapid AVR or be followed by an echocardiogram (echo) every 6-12 months to assess disease progression. Discrepancies have been reported in the care of severe AS. Goal: This study aims to evaluate adherence to guidelines, and identify factors associated with guidelines recommended care in patients with severe AS. Methods: All patients with a first echo report of severe AS diagnosis from January 2019 to December 2022 in a tertiary care academic health center were included. Adherence to guidelines was defined as undergoing AVR in 6 months or having a follow-up echo within 6-12 months of the index echo. Univariable and multivariable Cox proportional hazards models were performed to identify factors associated with guidelines recommended care. Patients who did not meet the endpoint and died before one year were censored at the time of death. Results: Of the 1655 patients included in the study (mean ± SD age: 77±12 years, 56% male, 80% white, 10% African-American, and 10% other race), 727 (43%) had AVR in 6 months, 184 (11%) had no AVR in 6 months but a follow-up echo within 6-12 months, and 744 (45%) did not achieve the guidelines recommended care. Two hundred and thirty-eight (14%) patients died within one year (178 patients did not meet guidelines). The multivariable Cox proportional hazards model (Table) revealed that younger age, lower LVEF, higher aortic valve mean gradient, cardiovascular history or risk factors, and having a cardiac specialty provider increased the rate of adherence to guidelines, while African-Americans and patients with renal failure were less likely to receive the guidelines recommended care. Conclusions: A substantial proportion of patients with severe AS does not receive the guidelines recommended care and follow-up. Factors including age, race, comorbidities such as renal failure, cardiovascular history and risk factors, provider specialty, and characteristics of the AS are associated with these discrepancies. These results call for urgent action to guide patient and provider behavior towards equitably implementing guideline-recommended valvular heart disease therapies.