tbuckley/cabot-search huggingface dataset:
Abstract 4140405: Hospital outcomes of patients with type 1 diabetes mellitus and moderate and severe congenital heart disease
Authors: Cameron Bose, Cindy Chin, Natalie Caryl, Omar Meziab, brent barber, Jennifer Andrews, Michael Seckeler
Journal: Circulation (2024)

Background: Advancements in life-saving treatment for patients with moderate and severe congenital heart disease (CHD) has led to the exponential growth of a novel population of individuals with CHD who previously did not survive beyond infancy. Little is known about the impact of other medical comorbidities on the overall health of these individuals. We sought to assess the effect of comorbid Type 1 diabetes (T1DM) on hospitalized individuals with CHD. Hypothesis: We hypothesized that individuals with CHD who had comorbid T1DM would have worse hospital outcomes than those without diabetes of any type. Methods: We conducted a retrospective review of the Vizient® Clinical Data Base (national, administrative database) for admissions from 10/2019-12/2023 with ICD-10 codes for moderate and severe CHD, aged 1 to 50 years. Data included: demographics, hospital outcomes and costs. Comparisons were made between those with ICD-10 codes for T1DM (E10 – E10.9) and those without any diabetes ICD-10 codes (E10 – E10.9, E11 – E11.9) using t-tests for normally distributed data, Mann-Whitney U test for non-normally distributed data and χ 2 for categorical data. Results: There were 64,189 CHD admissions, 846 (13.2%) with T1DM. Details are shown in Table 1. The T1DM group were younger, had a higher prevalence of Whites (consistent with known T1DM epidemiology), higher in-hospital mortality and lower hospital costs. Conclusions: This review of a national administrative database has found that hospitalized individuals with CHD and comorbid T1DM are hospitalized at younger ages and are at increased risk for in-hospital mortality. Despite this, hospital costs are lower. This suggests an additional negative effect of T1DM compared to CHD alone. Further studies are needed to examine potential interventions to reduce mortality in this population.
Abstract 4140442: Hidden in Plain Sight: Mavacamten’s Role in Unmasking Structural Abnormalities in Obstructive Hypertrophic Cardiomyopathy
Authors: Tanzim Bhuiya, Ji-Cheng Hsieh, Joshua Gilman, John Makaryus, Ronald Wharton
Journal: Circulation (2024)

Goals: Mavacamten not only promotes favorable cardiac remodeling in obstructive hypertrophic cardiomyopathy but can also unmask additional underlying structural abnormalities. Description of Case: An 80-year-old man with atrial fibrillation and basal septal hypertrophy with an intracardiac defibrillator, presented due to six months of exertional dyspnea. Transthoracic echocardiography (TTE) revealed severe basal septal hypertrophy (1.7cm) and systolic anterior motion (SAM) of the anterior mitral valve leaflet (peak LVOT gradient 104 mm Hg; Figure 1) . The patient was treated with metoprolol but presented again one month later with recurrent postural syncope. The metoprolol dosage was increased, and the patient was initiated on mavacamten. 12 weeks after initiation of mavacamten, surveillance TTE demonstrated a LVOT gradient of 7 mmHg at rest and 11 mmHg during Valsalva maneuver, and a basal septal wall thickness of 1.0 cm . Severe mitral regurgitation was noted with the mechanism identified as both Carpentier type I and II. The primary etiology of the regurgitation was determined to be P3 prolapse (Figure 2) . There was no longer evidence of SAM. The patient remained symptomatic and was referred to cardiothoracic surgery for mitral transcatheter edge-to-edge repair (mTEER). Post procedure, the patient’s dyspnea resolved. TTE showed the implanted Mitraclip with trace intra-valvular mitral regurgitation (Figure 3). Discussion: This patient likely had a multifactorial cause of dyspnea. Mavacamten improved the patient’s basal septal hypertrophy and SAM. Subsequent TTE revealed a previously undetected mitral regurgitation jet which was only apparent after the use of mavacamten. This finding led to resolution of symptoms with mTEER.
Abstract 4140448: Pericardiocentesis Outcomes in Patients With Chronic Kidney Disease : A Nationwide Analysis from the United States
Authors: Manoj Ghimire, Sajana Poudel, Karun Shrestha, Kalpana Ghimire, Salomon Chamay, Prakriti Subedi, Sameh Nassar, Oshna Pandey, Ninda Sherpa, Dinesh Kadariya, Salim Baghdadi
Journal: Circulation (2024)

Introduction: Pericardial effusions are common among patients with renal disease, especially those with advanced chronic kidney disease (CKD). This population frequently experiences uremic pericarditis, dialysis-associated pericarditis, and pericardial effusion. The natural history of pericardial effusions in the context of renal disease is highly variable. Aggressive hemodialysis can lead to resolution in some cases, whereas others may require immediate drainage for optimal management. Despite these clinical observations, there is a paucity of comprehensive literature evaluating the outcomes of pericardiocentesis in patients with CKD. Hypothesis: We hypothesize that pericardiocentesis in CKD patients associated with poor outcomes compared to patients without CKD. Methods: A retrospective observational study was conducted utilizing a national patient sample database from 2016-2021. Patients who underwent pericardiocentesis were identified using ICD-10 PCS codes. The study compared various demographics and clinical characteristics between patients with or without CKD. Results: A total of 126,834 adults who underwent pericardiocentesis were included, of which 34780(27.4%) patients had CKD, 10, 956 (8.66%) patients had ESRD and 7145 (5.6%) patients were dialysis dependent. Patients with CKD were relatively older and had higher prevalence of comorbidities as shown in the below table. Complications such as cardiac arrest (6.6% vs. 4.35%, p&lt;0.01), cardiogenic shock (13.8% vs. 9.21%, p&lt;0.01), ventricular arrhythmia (7.95% vs. 6.37%, p&lt;0.01), acute kidney injury (41.45% vs. 24.55%, p&lt;0.01), and mortality (12.57% vs. 9.56%, p&lt;0.01) were significantly higher in CKD patients. The length of stay (11.3 vs. 8.6 days, p&lt;0.01) and total hospital charges ($189,799 vs. $153,831, p&lt;0.01) were also greater for CKD patients. Conclusions: Patients with CKD who underwent pericardiocentesis for pericardial effusion has significantly higher rates complications, and mortality, along with longer hospital stays and increased healthcare costs . Further research with evaluation of etiology of pericarditis, current medical management, and stratifying patients based on CKD severity and dialysis dependence is required to assess the better outcomes.
Abstract 4140337: Resting Heart Rate and Chronotropic Incompetence are Linked
Authors: Anita Li, Summer Samuels, Markus Meyer
Journal: Circulation (2024)

Background: Cardiac output reserve and exercise capacity are strong predictors of life expectancy. Chronotropic incompetence (CI) is the inability to reach an age appropriate maximum heart rate with exercise. CI reduces cardiac output reserve and exercise capacity, both of which increase all-cause mortality risk. Sinus node dysfunction may manifest as CI and abnormally low resting heart rate (RHR). The relationship between low RHR and CI has yet to be described. Purpose: We hypothesize that resting sinus bradycardia (low RHR) could be a predictor of chronotropic incompetence and reduced exercise capacity. Methods: The derivation cohort consists of 201 patients with normal Bruce protocol treadmill stress echocardiogram. Patients with ejection fractions &lt;50%, baseline or stress induced wall motion abnormalities, and valvular diseases were excluded. The confirmation cohort, which was obtained from the National Institute of Health, consisted of 3315 patients with normal Bruce protocol treadmill stress test results in the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) Trial. RHR and peak exercise heart rates (PHR) were tabulated. All patients were categorized based on whether their PHR reached 85% of age-predicted maximum heart rates (APMHR) by the Astrand formula (220 - age in years) and the Tanaka formula (208 - 0.7 x age in years). Results: The mean(SD) age in the derivation cohort was 60(±11) years old and 45% were female. 46/201 (23%) did not reach their APMHR. The mean(SD) RHR in CI patients was 65.6(±12) beats per minute (BPM), while it was 69.2 (±12) BPM without CI (p =0.04). In the confirmation cohort, the mean age was 60(±6.9) years old and 48% were female. 427/3315 (13%) did not reach their APMHR. The mean RHR in CI patients was 68.9(±12) BPM versus 74.0 (±13) BPM in the patients that reached APMHR (p &lt;0.001). The Tanaka formula revealed similar results (p &lt;0.001). Patients with RHR below or equal to 60 BPM were almost twice as likely to have CI (20%) when compared to patients with RHR over 60 BPM (11%), with a statistical significance of p &lt; 0.001. Patients with CI had a greater cumulative hazard ratio for death and hospitalizations due to myocardial infarction or unstable angina (Image 1). Conclusion: These results demonstrate that CI is linked to lower RHR. Below 60 BPM RHR may therefore be an indicator of sinus node dysfunction and CI, both of which predict a reduced exercise capacity and increase all-cause mortality risk.
Abstract 4140423: Advanced maternal age and association with major adverse cardiovascular events from NHANES from 1999 to 2018
Authors: Adhya Mehta, Olayinka Agboola, Danish Iltaf Satti, Colleen Harrington, Nandita Scott, Amy Sarma, Antonio Saad, Scott Sullivan, Kelly Epps, Michael Honigberg, Jamie Kennedy, Jared Spitz, Garima Sharma
Journal: Circulation (2024)

Introduction: Pregnancy at an advanced age is becoming increasingly common in developed countries. The relationship between advanced maternal age (AMA) (≥ 35 years) and major cardiovascular events (MACE) is not well studied. Therefore, we evaluated the association of AMA at the time of last childbirth with MACE in a large nationally representative sample. Methods: We analyzed data from the 1999–2018 National Health and Nutrition Examination Survey. Females aged ≥45 years with no missing pregnancy record were included in the analysis. Based on the age of their last childbirth, they were divided into 4 groups- those who delivered at &lt;35 years (GROUP 1), 35-40 years (GROUP 2), &gt;40 years (GROUP 3), and nulliparous (GROUP 4). MACE was defined as a composite of a history of congestive heart failure, coronary artery disease, stroke, or all-cause death. We assessed the association between these groups and MACE using univariate and multivariate logistic regression models. Results: Among 13,180 (weighted frequency = 53,636,595) females included in this analysis, 20% had a history of AMA (groups 2 and 3), 70.6% had no history of AMA (group 1), and 9.4% were nulliparous. Compared to nulliparous women, women with no history of AMA had an 83% higher odd of MACE with an OR 1.83 (95% CI 1.45 – 2.31), while those with history of childbirth between ages 35 – 40 years had a 84% higher odd of MACE with OR of 1.84 (95% CI 1.37 - 2.46), and women with childbirth &gt;40 had 2.7 higher odds of MACE (2.73, (1.87 - 4.00)). However, after adjusting for demographic characteristics and surrogates for social determinants of health such as income, food insecurity, and insurance status, as well as cardiovascular (CV) risk factors like alcohol use, smoking, and comorbidities such as diabetes, dyslipidemia, and hypertension, this association was attenuated. (Table 1) Conclusion: Our study did not find a significant independent association between the maternal age of last childbirth and MACE. This suggests that maternal age alone may not be the primary risk factor; the effect of AMA might be mediated by other CV, social risk factors, and parity. This warrants further investigation to better risk stratify women with AMA as a documented risk factor.
Abstract 4140535: High throughput screen reveals that atypical antipsychotics promote continual efferocytosis by antagonizing dopamine signaling and promoting vitamin A-dependent Arginase1 upregulation
Authors: Yoko Kojima, Zhongde Ye, Fudi Wang, Mozhgan lotfi, Shaunak Adkar, Caitlin Bell, Lingfeng Luo, Changhao Fu, Nick Leeper
Journal: Circulation (2024)

Introduction: Programmed cell removal, or efferocytosis, has been proposed as a method to dispose of unwanted cells that accumulate to promote diseases such as cancer, infection, and atherosclerosis. The defective efferocytosis process in advanced atherosclerotic plaque causes secondary necrosis and contributes to plaque vulnerability. Blockade of ‘don’t eat me’ molecules such as CD47 induces favorable vascular effects, but can induce the clearance of some healthy tissue such as RBCs. Accordingly, we conducted a high-throughput screen of about 3000 FDA-approved drugs and compounds, to identify new pro-efferocytic therapies that may have translational potential. Methods&amp;Results: Using flow cytometry-based phagocytosis assays with RAW 264.7 murine macrophages, we identified 8 candidate compounds that reproducibly increased efferocytosis. Subsequent validation assays using Incucyte live-cell imaging assay in RAW cells, primary cultured murine macrophages, and human macrophages allowed us to identify the atypical antipsychotic drug, thiothixene, as a promising candidate for clinical translation, which induced cellular clearance without changing macrophage apoptosis, migration or proliferation. Leveraging thiothixene’s known inhibitory effects on a wide range of neurotransmitters and catecholamines, we found that dopamine has a potent inhibitory effect on efferocytosis, which thiothixene could partially offset. Thiothixene induced macrophage polarization and Arginase1 upregulation, promoting continual efferocytosis. Mechanistically, RNA-sequencing revealed that thiothixene upregulated Stra6L, a receptor for retinol-binding protein that mediates cellular uptake of retinol. Retinol and all-trans retinoic acid upregulated Arginase1 expression and promoted efferocytosis, which could be reversed via knockdown of Stra6l. Conclusion: This unbiased screen identified unanticipated anti-efferocytic properties of dopamine, while highlighting the translational potential of a generic, FDA-approved anti-psychotic drug. This therapy may represent a novel method for promoting continual efferocytosis and the disposal of unwanted cells that otherwise can promote a range of clinical disorders including atherosclerosis.
Abstract 4140074: Risk of the Post-Partum Period Among Women with Diagnosed and Treated Type 2 Long QT Syndrome (LQT2)
Authors: Raquel Neves, Sahej Bains, Johan Bos, John Giudicessi, Michael Ackerman
Journal: Circulation (2024)

Background: Long QT syndrome (LQTS) is a potentially lethal cardiac channelopathy. Among women with LQT2, the post-partum period has been considered high risk for cardiac events. However, whether this risk persists after establishing their diagnosis and implementing their LQT2-directed treatment program remains to be determined. Objective: To describe the management and outcomes of LQT2 women during the 9 months post-partum period. Methods: A retrospective analysis of 1869 patients with LQTS treated and evaluated at a tertiary center specializing in Genetic Heart Disease from January 2000 to November 2023 was performed to identify women with diagnosed and treated LQT2 who had a pregnancy during follow-up. Data were abstracted for patient demographics, clinical characteristics, symptomatic status, and treatment plans before and after pregnancy. Results: Overall, 30 pregnancies occurred in 22 women with LQT2. Their average QTc was 489 ± 34 ms with 7 patients (32%) having a resting QTc &gt; 500 ms. Prior to their first post-partum period, 5/22 (23%) were symptomatic with 2 (9%) experiencing a LQT2-triggered sudden cardiac arrest (SCA). Before their post-partum period, their LQT2-directed therapy comprised preventative measures only in 7 (23%), drug therapy in 16 (53%), combination therapy in 7 (23%), and 10 women (43%) had an implantable cardioverter defibrillator (ICD). Pre-emptive treatment intensification was done for 24/30 post-partum periods. Only a single VF-terminating ICD therapy occurred in 1 (3%) of the 30 post-partum periods involving a 21-year-old with p.Lys610Asn-KCNH2 variant, QTc = 490 ms, and a pre-diagnosis presentation of seizures. Conclusion: Although the post-partum period is regarded as a ‘high risk’ window of time for women with LQT2, the risk of a LQT2-triggered cardiac event after diagnosis and implementation of contemporary therapies is very low. This designation of “high risk” among correctly diagnosed and treated women is misleading and generates inappropriate and unnecessary anxiety.
Abstract 4140554: Epigenetic Activation of Endothelial to Mesenchymal Transition Links Endothelial Dysfunction to Atrial Fibrillation in Lamin A/C Cardiomyopathy
Authors: Asia Owais, Hanna Chen, Miles Barney, Arvind Sridhar, Abhinaya Baskaran, Elif Kortan, Jaime DeSantiago, Mahmud Arif, Abul Islam, Mark Maienschein-Cline, Sang Ong, Dawood Darbar
Journal: Circulation (2024)

Introduction: Accumulating evidence supports a bidirectional association between atrial fibrillation (AF), and endothelial cell (EC) dysfunction; however, the underlying mechanisms remain elusive. Variants in LMNA , which encodes the nuclear envelope protein Lamin A/C, have been linked with AF. It is known that LMNA variants can cause atherosclerotic changes in blood vessels and increase the risk for stroke, however, it remains unclear if endothelial dysfunction creates an arrhythmogenic substrate for AF in the atria. Hypothesis: LMNA -S143P mutation induces endothelial to mesenchymal transition ( EndMT) in ECs which creates an arrhythmogenic substrate for AF by extracellular matrix (ECM) and ion channel remodeling. Methods: We generated and co-cultured human induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) and atrial cardiomyocytes (hiPSC-aCMs) from a large family harboring a pathogenic LMNA -S143P mutation ( Fig. A-B ) and performed functional characterization by an angiogenesis assay. Analysis of action potential duration (APD) (Fig. B) was performed by optical voltage mapping. Transcriptomic and epigenetic analysis was performed by RNA-sequencing and assay for transposase accessible chromatin and sequencing (ATAC-seq). Results: LMNA -S143P hiPSC-ECs show hallmarks of EC dysfunction with reduced angiogenesis ( Fig. C ), gene expression signature of EndMT, upregulation of ECM remodeling genes and downregulation of endothelial genes ( Fig. E ). Upstream regulator analysis identified TWIST-1 as a driver of EndMT (Fig. F) . ATAC-seq showed increased open chromatin at genes related to EndMT and identified TWIST-1 as one of the most significantly enriched transcription factors ( Fig. G-I ). Upregulated ATAC peaks were associated with inflammation and fibrosis pathways ( Fig. H ). Co-culture of LMNA -S143P hiPSC-ECs with wild-type hiPSC-aCMs induced APD heterogeneity (SD=0.03, 0.2, 0.01 for WT, LMNA -S143P, CRISPR-GC respectively, p&lt;0.05, n=6) ( Fig. D ). These changes were rescued by the CRSIPR-GC hiPSC-ECs. Conclusion: Our results suggest that epigenetic-driven EndMT due to a LMNA -S143P mutation promotes inflammatory and fibrotic remodeling in the atria and we identified TWIST1 as a potential therapeutic target.
Abstract 4140072: Icosapent Ethyl-Associated New Atrial Fibrillation Incidence compared to Omega-3 Fatty Acids: An Observational Cohort Study
Authors: Jyotirmoy Sarker, Samantha Patton, Michael Kim, Przemyslaw Radwanski, Mark Munger, Kibum Kim
Journal: Circulation (2024)

Introduction: Icosapent ethyl (IE), an ethyl ester derivative of eicosapentanoic acid (EPA), and omega-3 acid ethyl esters, an ethyl ester derivative of both EPA and docosahexaenoic acid (DHA), are approved as adjunct to statin therapy for reducing MACE in patients with elevated triglyceride levels. There are concerns regarding atrial fibrillation (AF) risk associated with IE. This study aims to assess the incidence of AF while receiving IE versus omega-3-acid ethyl esters (DHA/EPA), both alongside baseline statin therapy. Methods: In this retrospective cohort study, we used data from the Merative MarketScan Commercial Claims and Medicare Supplemental Databases (2013-2021). Adult patients on statin therapy who initiated either IE or DHA/EPA were identified using outpatient dispensing records. Patients with an AF diagnosis during the one-year baseline period were excluded. Patients were followed for up to two years to assess the incidence of AF. Censoring occurred if there was treatment discontinuation, switching between treatments, end of enrollment, or end of the study. Patients experiencing events or being censored within the first 30 days were also excluded. Propensity score matching was used to create comparable groups, with exact matching on time periods (2013-2015, 2016-2018, and 2019-2021). Using Cox proportional hazard regression model, we calculated hazards ratio of the onset of AF for IE versus DHA/EPA. Results: The analytic cohort consisted of 17,638 matched pairs. Patients in both groups had a median age of 56 years. Male patients accounted for a 65.7% of the IE group and 64.5% of the DHA/EPA group. Baseline cardiovascular risk factors were well matched between both groups. The 2-year cumulative incidence of AF for IE and DHA/EPA groups were 5.322% and 3.994%, respectively, resulting in a HR of 1.257 [95% CI,1.159-1.364], p=0.0032. (Figure 1) Conclusions: IE is associated with a higher risk of AF compared to DHA/EPA combined products, indicating the need for careful risk-benefit discussion between clinicians and patients considering IE therapy.
Abstract 4140416: Impact of reduced right ventricular function on prognosis or heart failure hospitalization in wild-type transthyretin cardiac amyloidosis
Authors: Ayumi Omuro, Shinichi Okuda, MASAKI TAMITANI, Junya Nawata, Yusuke Nakashima, Fujita Miho, Kaori Murakawa, Moe Uno, Uchida Masamune, Takayuki Okamura, Motoaki Sano
Journal: Circulation (2024)

Background： Wild-type transthyretin cardiac amyloidosis (ATTRwt-CA) is a disease that is increasingly diagnosed through non-invasive diagnostic procedures, including echocardiography and 99mTc-pyrophosphate scintigraphy, and advances in medical treatment. However, echocardiographic prognostic markers of ATTRwt-CA have not been fully clarified. Aims: The aim of this study was to evaluate physical findings, biomarkers, and echocardiographic parameters related to prognosis and heart failure (HF) in patients with ATTRwt-CA. Methods: Thirty-two consecutive patients diagnosed with ATTRwt-CA by myocardial biopsy at Yamaguchi University Hospital from April 2021 to March 2023 were included. Echocardiographic parameters associated with composite adverse outcomes including all-cause mortality or hospitalization for HF were examined. Results: During an average follow-up period of 542 days,３patients died and 3 patients were hospitalized for HF. The proportion of male was 91%, the mean NYHA was 1.9, and 44% had a history of HF hospitalization. The average of left ventricular ejection fraction (LVEF) was 44.5%, and wall thickness averaged 13.5mm at interventricular septum. At univariate analysis, systolic blood pressure（systolic BP: 121mmHg vs. 99mmHg, p&lt;0.01）, diastolic BP (68mmHg vs. 56mmHg, P&lt;0.05), NT-pro BNP (2304pg/ml vs. 5875pg/ml, p&lt;0.01), right ventricular (RV) basal diameter (37mm vs. 41mm, p&lt;0.05), tricuspid annular plane systolic excursion (16.5mm vs. 14.5mm, p&lt;0.05), right ventricular fractional area change (38% vs. 28%, p&lt;0.01), right atrial volume index (37.2ml/m2 vs. 55.2ml/m2, p&lt;0.05) were significantly associated with the composite adverse outcome. Left-sided echocardiographic parameters including LV diameter, LVEF, stroke volume index, E/E’, global longitudinal strain, and left atrial reservoir strain were not associated with outcome. Conclusion: In ATTRwt-CA, in addition to NT-pro BNP and BP, the presence of decreased RV function may correlate with prognosis or HF admission.