tbuckley/cabot-search huggingface dataset:
Abstract 14122: Evaluating Gender Diversity in Principal Investigators of Cardiac Electrophysiology Clinical Trials
Authors: Shirin Sadri, Grace A Soontornviwath, Alice Ku, Crystal O Bernardez, Tawfique Ali, Ananya Khosla, Khusbu K Adhikari, Angelina S Duran, Joseph-Kelvin Igwe, Kira Clark, Erin Rose R Cruz, Muhammed Y Idris, Peter Poullos, VJ Periyakoil, Bryant Lin, Latha Palaniappan, Celina M Yong, Anekwe Onwuanyi, Melvin Echols, Paul J Wang, Ridhima Kapoor
Journal: Circulation (2023)

Background: Importance of diversity in clinical trial participants has been recently highlighted. Though clinical trials led by women principal investigators (PIs) are more likely to enroll diverse participants, the proportion of trials led by women PIs is unknown. Objective: To evaluate gender distribution among PIs who conduct NIH and industry-funded clinical trials in cardiac electrophysiology (EP). Methods: NIH and industry-funded trials in the clinicaltrials.gov registry completed between 1/1/2002 and 12/31/2021 in atrial fibrillation (AF), implantable cardioverter defibrillators (ICDs), pacemakers (PPMs), sudden cardiac arrest (SCA), and ventricular tachycardia (VT) were included. PI names and associated institutions were used to determine gender pronouns on institutional websites or social media. Trials with unidentifiable PI gender were categorized as unknown. Results: 51 NIH-funded and 429 industry-funded trials in AF, SCA, VT, ICDs, and PPMs and 573 total PIs were identified. 128 trials (26.7%) and 123 PIs (21.5%) had unknown PI gender. 16.4% of all trials in which PI gender was known were led by women. 9/49 (18.4%) NIH and 49/295 (16.6%) industry trials were led by women. VT trials had the lowest proportion women-led (NIH: 0/4, 0%; industry: 3/26, 11.5%), whereas PPM trials had the highest proportion women-led in both NIH (3/5, 60%) and all trials (12/48, 22.2%). Of the group with the largest number of trials (AF), 12.9% were women-led (22/170) (Table). Of 450 PIs across all trials whose gender was identified, 14.4% were women. The proportion of women PIs decreased non-significantly over time. Studies between 2002-2011 were 16% women-led, and in 2012 or later this reduced to 13% X 2 (1, N = 450) = 0.81, p &gt; .05. Conclusion: The proportion of cardiac EP clinical trials led by women PIs remains low and has not increased. Urgent efforts are needed to implement strategies to increase leadership roles in clinical trials for women in cardiac electrophysiology.
Abstract 13020: Trend and Disparities in Cardiovascular Death in Amyloidosis: A Population-Based Retrospective Study in the United States From 1999 to 2020
Authors: Min Choon Tan, Yong Hao Yeo, Boon Jian San, Reza Arsanjani, Julie Rosenthal, Kwan S Lee
Journal: Circulation (2023)

Background: Despite advancements in the management of cardiac amyloidosis, the contemporary estimates of the cardiovascular deaths (CVDs) in amyloidosis are not well-established. Objective: This study sought to assess the longitudinal trends of CVDs with comorbid amyloidosis and analyze the disparities in mortality in terms of race, gender, and geographical location. Methods: We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database and performed serial cross-sectional analyses of national death certificate data for cardiovascular mortality with comorbid amyloidosis among patients aged 25 and above. Diseases of the circulatory system (ICD-10 I00-I99) were listed as the underlying cause of death, and amyloidosis (ICD-10 E85) as contributing cause of death. We calculated age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and determined the trends over time by estimating the annual percent change using the Joinpoint Regression Program. Results: In the 22-year study period, 4,145 CVDs with comorbid amyloidosis in the United States were identified between 1999 and 2020. The AAMRs increased significantly from 0.69 per 1,000,000 individuals in 1999 to 2.13 per 1,000,000 individuals in 2020 (p&lt; 0.05), with an annual percent increase of +3.92. The AAMRs for the span of 22 years were higher in males than females (1.66 vs. 0.75, p&lt;0.05). When stratified by race, African American populations had the highest cumulative AAMR (2.34) compared to other racial groups. In terms of urbanization, the AAMR was significantly higher in the urban regions compared to the rural areas (1.15 vs. 0.91, p&lt;0.05). Conclusion: The AAMRs from CVDs with comorbid amyloidosis have increased significantly over the past two decades, with significant disparities in male and African American individuals. This emphasises the need of further research in the development of effective treatments for amyloid heart disease.
Abstract 11430: A Bad Break: Cardiogenic Shock Complicated by an Intracardiac Foreign Body
Authors: Andrew Hendrix, Kevin Li, Josh Chang, Rishi Sukhija, Manisha Das
Journal: Circulation (2023)

Introduction: We report a case of cardiogenic shock complicated by an intracardiac foreign body. This is a rare occurrence during a dangerous cardiovascular disease process which necessitated urgent multidisciplinary management. Case: A 54-year-old female with a history of hypertensive cardiomyopathy and breast cancer was not improving during a hospitalization for acutely decompensated CHF and atrial flutter with RVR. Right heart catheterization demonstrated cardiogenic shock, with a foreign body noted in the right atrium favored to be a fragment of the left subclavian port catheter also seen on fluoroscopy. This object was present on admission imaging but likely mistaken as external artifact. Coronary angiography revealed severe multi-vessel CAD. A multidisciplinary team discussed the timing and modality of foreign body removal, electing to prioritize hemodynamic optimization before intervention. Once stable, the patient underwent successful endovascular removal of the catheter fragment with immediate improvement of her heart rhythm. She remained in sinus rhythm until discharge home in stable condition. Discussion: This episode of cardiogenic shock may have been precipitated by an arrhythmogenic intracardiac foreign body. However, medication non-adherence and severe CAD on angiography suggested a multifactorial etiology, justifying a delay in the removal of the foreign body until shock had resolved. Additionally, the catheter fragment present on admission imaging should have been identified earlier as a contributing factor. Timely recognition and removal of the fragment may have prevented the hemodynamic decompensation of the patient. Conclusion: This case demonstrates the efficacy of delaying the removal of an intracardiac foreign body in favor of hemodynamic optimization in patients with cardiogenic shock, while obviating the need for maintaining a broad differential when determining the underlying etiology of decompensated heart failure.
Abstract 105: Rural-Urban Differences for Integrated First Responder and Drone Automated External Defibrillator Delivery in North Carolina
Authors: Jamal Chu, Benjamin Leung, Audrey L Blewer, Konstantin Krychtiuk, Darrell Nelson, Stephen Powell, Bryan F McNally, Christopher B Granger, Joseph P Ornato, Daniel B Mark, Timothy Chan, Monique A Starks
Journal: Circulation (2023)

Background: Early defibrillation for out-of-hospital cardiac arrest (OHCA) can improve survival significantly, but timely access to AEDs remains a barrier especially in rural areas. We analyzed whether differences exist between urban and rural areas for a proposed program of first responder (FR) and drone AED delivery in North Carolina. Methods: Using CARES registry data, we identified OHCAs in 48 counties between Jan. 2013-Dec. 2019. We applied a hypothetical intervention in which 1) all FRs were provided AEDs and 2) a network of AED-carrying drones was optimized within each county to maximize &lt;5-minute response times (defined as the interval from 9-1-1 call receipt to arrival of an AED via EMS, FR, or drone). Within each county, we classified census tracts by rural population with &lt;25% as urban, 25-75% as mixed, and &gt;75% as rural. We included only counties with ≥10 OHCAs per year in both rural and urban census tracts to compare resource allocation for counties with large geographic variation. Historical and intervention response times stratified by rurality were compared via the Wilcoxon signed-rank test. Results: We included 19 counties and 8,955 OHCAs (5,754 urban, 3,201 rural). The historical median response time was 6.9 mins [IQR: 5.1-8.7] in urban census tracts and 9.4 mins [IQR: 7.0-12.1] in rural tracts. The FR + drone intervention reduced estimated median response times by 42% to 4.0 mins [IQR: 3.1-5.0] in urban areas and by 24% to 7.1 mins [IQR: 5.2-9.4] in rural areas. Five-minute coverage improved from 24% to 77% for urban areas and 10% to 23% for rural areas. All counties showed significant improvement in response time for both urban and rural populations (p&lt;0.01). Conclusion: Deployment of AEDs by FR and drones optimized for 5-minute coverage was estimated to improve AED response more so in urban areas than rural areas. Other optimization parameters are needed to reduce inequality between urban and rural response times in areas with large geographic variation.
Abstract 18534: Catheter-Directed Mechanical Thrombectomy: A PERTinent Paradigm Shift
Authors: Bianca Honnekeri, dhriti patel, Scott J Cameron, Pulkit Chaudhury, Leben Tefera
Journal: Circulation (2023)

Introduction: The emergence of catheter-directed mechanical thrombectomy (MT) heralded a paradigm shift in the management of pulmonary embolism (PE). There is a paucity of data on the degree to which the availability of this modality has impacted clinical-decision making by the multidisciplinary Pulmonary Embolism Response Team (PERT). We examine data from a single center experience at a large tertiary hospital to shed light. Research Question: How does the recent emergence of MT as a therapeutic strategy impact the approach of a PERT team? Aim: To examine the degree to which the integration of MT into the clinical decision-making algorithm for PE management has impacted the treatment course recommended by a PERT team. Methods: A retrospective analysis was performed to compare PERT recommendations in a contemporary cohort (10/2020-3/2023) to a historical cohort (1/2015-6/2016) prior to the availability of newer generation mechanical thrombectomy catheters in the same institution. Results: The contemporary cohort consisted of 306 patients, of which 50% were treated with advanced therapies including MT, catheter-directed lysis, systemic tPA, or ECMO. In the historical cohort, 28% of patients received advanced therapies. Of those treated with advanced therapies, 84% were MT and 1% were catheter-directed lysis in the contemporary cohort compared to 6% MT and 31% catheter-directed lysis in the historical PERT cohort. Conclusion: The integration of MT into the PERT decision-making process portends a new era in the management of PE. At our center, it significantly expanded the ambit of advanced therapies, such that a majority of patients now receive some form of advanced therapy, rather than anticoagulation alone. This is in stark contrast with the pre-MT era. These findings underscore the importance of a PERT team’s ability to adapt to evolving treatment modalities and highlights the need for continued multidisciplinary expertise in optimizing care for PE patients.
Spesolimab for the Treatment of Generalized Pustular Psoriasis
Authors: Diana Bernardo, Diamant Thaçi, Tiago Torres
Journal: Drugs (2023)

Generalized pustular psoriasis (GPP) is a rare but severe skin inflammatory disorder characterized by the eruption of widespread sterile neutrophilic pustules, often accompanied by systemic inflammation. Given its life-threatening potential, GPP requires prompt accurate diagnosis and effective treatment, but its rarity and relapsing-remitting nature pose challenges in performing large-scale randomized controlled clinical trials. Established international guidelines are currently lacking and management guidance often follows that for plaque psoriasis. However, while it can co-exist with plaque psoriasis and has traditionally been classified as a most severe form of psoriasis, GPP is now recognized as a distinct entity, with its own clinicopathological, autoinflammatory, immunologic and genetic features. Research conducted over the past decade revealed that an imbalance of interleukin (IL)-36 signaling favoring the proinflammatory activity is the central driver of the pathogenesis of GPP, thereby laying the groundwork for the development of targeted therapies for the disease. This article reviews the evidence thus far on spesolimab, a selective humanized antibody against the IL-36 receptor that was recently licensed in Europe and the United States for the treatment of GPP flares in adults. In phase II, randomized controlled clinical trials, spesolimab led to rapid and effective skin clearance in patients experiencing a GPP flare and demonstrated superiority to placebo in preventing flares for up to 48 weeks with maintenance treatment, with reassuring safety and tolerability profiles. Spesolimab is considered to be a first-in-class medication establishing itself as the standard of care for the treatment of GPP flares, thus changing the paradigm of the management of GPP to a new era of scientifically- and evidence-based targeted therapy for this distinctive disease.
Abstract 18422: Long-Term Changes in Tricuspid Regurgitation and Right Ventricular Function in Patients Undergoing Lung Transplantation: A 5-Year Study
Authors: Rehan Karmali, Essa Hariri, Bianca Honnekeri, Olivia Noall, MARIE BUDEV, Kenneth McCurry, Venu Menon
Journal: Circulation (2023)

Introduction: The presence and severity of tricuspid regurgitation (TR) has been associated with cardiovascular morbidity and mortality in a number of disease states. The impact of TR on future outcomes in patients selected for lung transplantation has not been adequately evaluated. Methods: We retrospectively evaluated patients who underwent lung transplant at Cleveland Clinic between 2000 and 2022. Patients undergoing multi-organ transplant, CABG, surgery or valve repair were excluded. The presence of baseline TR and its severity was assessed on the closest echo antecedent to transplantation utilizing an IRB approved Echocardiography registry. We used survival analyses to assess our primary outcome of all-cause mortality. We also assessed distribution of TR severity over short and long-term follow up. Results: We evaluated pre-transplant echocardiograms in 1490 individuals who had a mean age of 55 years; 60% being female. The proportion of 0, 1+, 2+, 3+ and 4+ TR was 56%, 25%,12%, 4% and 3% respectively. During a 5-year post-transplant follow-up period, the presence of severe TR pre-operatively was associated with an increased risk for all-cause mortality [aHR 2.1, 95% CI (1.09, 5.1); p = 0.029]. The distribution of TR severity did not appear to be significantly modified by the procedure at 6, 12, 24, 36, 48 and greater than 48-month follow up [OR 1.32, 95% CI (1.76), p = 0.062). Conclusions: Pre-operative TR severity as measured by echocardiography was associated with an increase in all-cause mortality in patients undergoing lung transplant, but the distribution of TR severity did not significantly differ on long-term post-transplant follow up.
Abstract 13050: Dysfunctional Endothelial-Subcutaneous Adipocyte Cross-Talk in Patients With Reduced Ejection Fraction Heart Failure and Type 2 Diabetes Mellitus
Authors: Oliver I Brown, Katherine I Bridge, Natallia Makava, Sam Straw, Cheukyau Luk, Pradeep Wijayagoonawardana, Muzahir Tayebjee, michael drozd, John Gierula, Klaus K Witte, Richard Cubbon, Stephen B Wheatcroft, Mark T Kearney
Journal: Circulation (2023)

Introduction: Normal subcutaneous adipose tissue (SAT) function is critical to metabolic homeostasis and is dependent on normal microvascular endothelial cell (MVEC) function. Heart failure with reduced ejection fraction (HFrEF) and type 2 diabetes mellitus (T2DM) have a synergistic deleterious relationship and of relevance to this metabolic dysregulation may drive HFrEF progression in T2DM. Detailed phenotyping of SAT microvasculature in this population is lacking. Aims: To examine SAT MVEC function and cross talk between SAT MVEC and adipocytes in patients with HFrEF and T2DM. Methods: Pectoral SAT biopsies were taken from HFrEF patients with and without T2DM undergoing pacemaker implant. SAT was examined for angiogenic potential, vascularity, adipocyte morphology and inflammatory markers. MVEC were isolated from SAT and characterised for metabolic, mitochondrial and proliferative capacity, angiogenic potential and senescence. The direct effect of altered SAT MVEC physiology in T2DM on healthy adipocytes was examined using indirect (conditioned media) and direct (co-culture) techniques. Results: We recruited 51 people with HFrEF of whom 21 (41%) had T2DM (HFDM). There was no difference in age, sex, or body mass index between groups. Macroscopically, SAT from patients with HFDM had impaired angiogenesis and increased fibrosis compared to SAT from HFrEF patients alone. SAT MVEC from patients with HFDM had lower metabolic activity, ATP production, proliferation; increased senescence and impaired angiogenesis. Healthy adipocytes co-cultured with SAT MVEC from HFDM patients had significantly increased expression of interleukin-6 and reduced uptake of 2-NBD-glucose compared to HFrEF alone. Conclusions: Cross talk between SAT MVEC from HFDM patients and healthy adipocytes leads to a deleterious alteration in adipocyte phenotype. Future work identifying the mechanism of SAT MVEC to adipocyte cross talk may identify novel therapeutic targets for patients with HFrEF and/or T2DM.
Abstract 15504: Impaired Branched-Chain Amino Acid Catabolism is Associated With Chemotherapy-Induced Heart Failure and Rescued by Metformin
Authors: Feixiong Cheng, Jessica Lal, Yuan Hou, Jonathan D Smith, David R Van Wagoner, Patrick H Collier, Mina K Chung
Journal: Circulation (2023)

Introduction: Heart failure resulting from cancer therapies represents a major cause of morbidity in cancer survivors. Interventional strategies to prevent and treat heart dysfunction in cardio-oncology patients continue to remain a challenge. Hypothesis: We posit that Branched-Chain Amino Acid Catabolism (BCAA) catabolism dysfunction is a likely causal mechanistic pathway in the pathogenesis of CTHF. Methods: In this study, we leveraged electronic health records , human-induced pluripotent stem cell ( iPSC )-derived cardiomyocyte model-based mechanistic studies, murine models, and network medicine-basedtranscriptomics analytic methodologies, to suggest that rescuing BCAA catabolic dysfunction is a promising approach for managing chemotherapy-induced heart failure, using doxorubicin as a prototypical example. Results: In our large-scale cardio-oncology cohort, we observed a significant incidence of heart dysfunction and abnormal NT-proBNP levels among patients treated with doxorubicin. Using murine heart failure models, we identified significant correlations between the abundance of branched-chain amino acids (isoleucine, leucine, and valine) and cardiac dysfunction after doxorubicin exposure. Mechanistic observations in human-induced pluripotent stem cell (iPSC)-derived cardiomyocyte models further support impaired branched-chain amino acid (BCAA) catabolism by doxorubicin. Through metabolite-enzyme network analysis, we identified metformin as a repurposable drug capable of restoring branched-chain amino acid catabolism, thereby improving mitochondrial function. Human iPSC-based mechanistic studies revealed that metformin combined with doxorubicin resulted in improved insulin signaling, endothelial cell reprogramming, increased RARA gene expression (a key doxorubicin-induced heart failure GWAS gene) and reduced pro-fibrotic signaling. Furthermore, we demonstrate that metformin improved murine cardiac function following doxorubicin exposure. Conclusions: Our findings utilized electronic health records, iPSC-based mechanistic studies, and murine models to suggest that BCAA catabolic dysfunction may be a promising approach for managing chemotherapy-induced heart failure.
Abstract 11415: Integrative Metabolomics Differentiate Coronary Artery Disease, Peripheral Artery Disease, and Venous Thromboembolism Risks
Authors: Jiwoo Lee, Thomas Gilliland, Satoshi Koyama, Tetsushi Nakao, Jacqueline S Dron, Kim Lannery, Megan Wong, Gina Peloso, Whitney Hornsby, Pradeep Natarajan
Journal: Circulation (2023)

Rationale: Venous and arterial cardiovascular conditions, such as venous thromboembolism (VTE), coronary artery disease (CAD), and peripheral arterial disease (PAD), are genetically correlated. Interrogating distinct and overlapping mechanisms may shed new light on disease mechanisms. Objective: In this study, we aimed to: identify and compare (1) epidemiologic and (2) causal, genetic relationships between metabolites and CAD, PAD, and VTE. Methods: We used metabolomic data from 95,402 individuals in the UK Biobank, excluding individuals with prevalent cardiovascular disease. Logistic regression models adjusted for age, sex, genotyping array, first five principal components of ancestry, and statin use estimated the epidemiologic associations of 249 metabolites with incident CAD, PAD, or VTE. Bidirectional two-sample Mendelian randomization (MR) estimated the causal effects between metabolites and cardiovascular phenotypes using genome-wide association summary statistics for metabolites (N = 118,466 from UK Biobank), CAD (N = 184,305 from CARDIoGRAMplusC4D 2015), PAD (N = 243,060 from Million Veterans Project) and VTE (N = 650,119 from Million Veterans Project). Multivariable MR (MVMR) was further performed in subsequent analyses. Results: We found that 194, 111, and 69 metabolites were epidemiologically associated (P &lt; 0.001) with CAD, PAD, and VTE, respectively. Metabolomic profiles exhibited variable similarity between disease pairs: CAD and PAD (N = 100, R 2 = 0.499), CAD and VTE (N = 68, R 2 = 0.455), and PAD and VTE (N = 54 shared associations, R 2 = 0.752). MR revealed 28 metabolites that increased risk for both CAD and PAD and 2 metabolites that increased risk for CAD but decreased risk for VTE. Despite strong epidemiologic overlap, no metabolites had a shared genetic relationship between PAD and VTE. MVMR revealed several metabolites with shared causal effects on CAD and PAD related to cholesterol content within very-low-density lipoprotein particles. Conclusions: While common arterial and venous conditions are associated with overlapping metabolomic profiles, MR prioritized the role of remnant cholesterol in arterial diseases but not venous thrombosis.