tbuckley/cabot-search huggingface dataset:
Abstract 4143019: Fetuses with Congenital Heart Disease and Placental Malperfusion Have Adverse Outcomes and <i>De Novo</i> Variants in Key Placental Developmental Pathways
Authors: Rebecca Josowitz, Stacy Woyciechowski, Rebecca Linn, Jack Rychik, J Gaynor, Ramakrishnan Rajagopalan, Nancy Spinner
Journal: Circulation (2024)

Background: Placental malperfusion (PMP), and perturbation of shared developmental pathways between the fetal heart and placenta, may play a role in the development and outcomes of congenital heart disease (CHD). We hypothesize that genomic variation in pathways involved in vascular or placental development underlie PMP in CHD, which in turn impacts outcomes. Methods: Fetuses were diagnosed prenatally with structural CHD in our Fetal Heart Program. Maternal characteristics, neonatal biometrics, genomic diagnoses, and outcomes data were reviewed. Placentas with PMP met pathological criteria according to the Amsterdam Placental Workshop classification for maternal or fetal vascular malperfusion, or placental weight &lt;10% for gestational age. All probands (and available parents) underwent genome sequencing and rare, predicted deleterious exonic or putative splicing single nucleotide variants and small insertion deletions were identified from whole genome sequencing data. De novo variants were identified from trios (n = 252) and pathway enrichment analysis was performed. T-tests/Mann-Whitney or Chi-squared/Fishers exact tests were performed with p-value &lt; 0.05 considered significant. Results: Of 299 fetuses with CHD, 51% had evidence of PMP (n=153). There were no significant differences in baseline characteristics or CHD subtype of those with or without PMP. Non-syndromic fetuses with PMP (n=118) had decreased birth weight (3335g vs 3000g; p&lt;0.001), length (49cm vs 48cm; p&lt;0.001), head circumference (34cm vs 33cm; p&lt;0.001), longer index hospitalization (15d vs 21d; p=0.02), and a trend towards increased mortality (6% vs 12.7%; p=0.08). The burden of vascular developmental pathway or de novo variants (34% vs 39%) was similar between groups and not associated with adverse outcomes. Genes with de novo variants were significantly enriched in cardiac developmental pathways in all CHD fetuses, however those with PMP demonstrated distinct enrichment in Notch signaling ( NOTCH1, NOTCH3, DLL4, SMAD6, VIM, TIE1 ) and collagen/extracellular matrix biosynthesis ( COL4A4, FN1, MMP2 ), genes critical for trophoblast and placental vascular development. Conclusion: CHD fetuses with PMP have impaired fetal growth, longer hospital length of stay, and a trend towards increased mortality. In CHD fetuses with PMP, rare, deleterious de novo variants were significantly enriched in several key placental developmental pathways, which may represent key mechanisms underlying PMP in CHD.
Abstract 4142149: A 10 Year Report on Fontan Candidacy
Authors: Marissa Adamson, Mohan John, Pranay Nayi, Shriprasad Deshpande, Matthew Ferguson, Kevin Maher, Paul Chai, Asaad Beshish
Journal: Circulation (2024)

Background: As patients progress through the single ventricle palliation, changing hemodynamics and non-cardiac conditions can prevent completion of Fontan. We sought to determine the incidence of completion of Fontan at our institution and to investigate the reasons for non-Fontan candidacy. Methods: Institutional database was queried to identify patients who underwent single ventricle palliation from 2010 to 2020. Patients who underwent stage 2 palliation were included for analysis. The primary outcome of interest was reason for non-Fontan candidacy or reason for delayed Fontan. Results: 526 patients who reached stage 2 single ventricle palliation were analyzed. 378 (71.9%) underwent Fontan procedure or were referred for Fontan before the age of 4-years-old at our center at the time of the study (Figure 1). 19 patients died prior to the typical age of Fontan and 38 were lost to follow up. Of the remaining 91 patients, 21 (23.1%) had a 1.5 or 2 ventricle repair, 12 (13.2%) had a Fontan at another center, and 29 (32%) had a late Fontan. Most patients with late Fontan were due to provider practice variation (22), whereas there were only 3 patients with medical conditions delaying pre-Fontan testing, and 4 patients had a Kawashima. Only 3 patients out of the 12 who had Fontan at another center were for second opinions, whereas the remainder either moved or had surgery at another center due to family preference. Reasons for non-Fontan candidacy were divided into cardiac and respiratory sources. Cardiac reasons included severely depressed ventricular function (12), diastolic dysfunction (2), atrioventricular valve stenosis or regurgitation (7), and pulmonary vein stenosis (3). Respiratory conditions leading to non-Fontan candidacy included severe OSA (1), pulmonary arterial malformation (1), and pneumonectomy (2). There are 17 patients in the non-candidacy group who had a heart transplant or were listed for transplant at the time of the study. No patient in our study was deemed not a candidate for Fontan after stage 2 palliation for developmental delay or syndrome. Discussion: This study demonstrates that the reasons for non-Fontan candidacy after completion of stage 2 palliation are broadly due to hemodynamic and respiratory condition, with many patients who are not candidates developing severe ventricular dysfunction after stage 2. There is a subset of patients who either move, are lost to follow up, or are delayed due to provider practice variation.
Abstract 4142134: Temporal Trends in Implantation of Cardiac Electronic Devices Following Septal Reduction Therapy in Obstructive Hypertrophic Cardiomyopathy
Authors: Spandan Desai, Nicholas Roma, Megan Pattoli, Kashyap Shah, Shahrad Shadman, Eluwana Amaratunga, Lindsey Magid, Jamshid Shirani
Journal: Circulation (2024)

Background: Septal reduction therapy (SRT) options for obstructive hypertrophic cardiomyopathy (oHCM) include surgical myectomy (SM) and alcohol septal ablation (ASA). A significant proportion of these SRTs also concurrently receive an implantable cardioverter defibrillator (ICD). We aimed to compare recent temporal trends and outcomes in this SRT subset. Methods: National Inpatient Sample 2016-2021 was queried to identify adults with oHCM using appropriate ICD codes and procedure codes were obtained for SM with ICD placement and ASA with ICD placement respectively. Logistic regression was applied to compare in-hospital outcomes. Results: Between 2016-2021, there were 420 cases with SM and ICD placement and 185 cases with ASA and ICD placement. Cases with ASA with ICD were older (64.3 -vs- 52.4 years), more likely to be females (58.3% -vs- 40.3%, p=0.041). The proportion of annual SM with ICD placement rates continued to decrease from 2016 and 2021 (Table 1). In comparison to this, there was an increase in ASA with ICD placement rates each year. During the study period, a majority of ASA with ICD occurred in the northeast while the majority of SM with ICD occurred in the midwest. More than 90% of SRTs were performed at large urban teaching centers. ASA with ICD cases had a higher proportion of SRT complications including development of complete heart block (62.2% -vs- 41.7%, p&lt;0.001) but lower incidence of ventricular fibrillation (2.7% -vs-9.5%, p=0.003). ASA with ICD cases had a shorter length of stay (6.6 -vs- 10.9 days) and less total hospitalization cost ($240,792 -vs- $314,359). For both groups, major complications were uncommon and remained unchanged throughout this study period. Conclusion: Analysis of SRT groups in this retrospective database of hospital admissions was indicative of an overall decline in SM with ICD procedures from 2016 to 2021. Further analysis is needed to understand the impact of this trend on long term outcomes of oHCM patients.
Abstract 4142114: Significant Reduction in Left Atrial Epicardial Adipose Tissue Following Catheter Ablation for Atrial Fibrillation
Authors: Nadia Chamoun, Yaacoub Chahine, Ahmad Kassar, Hala Al Yasiri, Tori Hensley, Nazem Akoum
Journal: Circulation (2024)

Background: Atrial fibrillation (AF) is closely associated with obesity, and epicardial adipose tissue (EAT) has been proposed as a possible promoter of fibrosis and predictor of AF recurrence post-ablation. The impact of ablation on left atrial (LA) EAT, as well as that of LAEAT on ablation-induced scarring, have not been explored. Our aim was to assess changes in LAEAT volume following ablation and the association of LAEAT with ablation-induced scarring and AF recurrence. Methods: This is a single-center observational study of AF patients undergoing their first catheter ablation at the University of Washington. Cardiac MRIs were done pre- and post-ablation. LGE-MRI and Dixon sequences were used to assess ablation-induced scarring and LAEAT ( Panel A ). 3D atrial models of fibrosis and ablation-induced scar with superimposed EAT were created ( Panel B ). Patients were followed prospectively for AF recurrence. Results: We included 14 patients, aged 68 (60-74) years, 64% male, and 71% with paroxysmal AF. Radiofrequency ablation was performed in 8 (57%) patients and cryoballoon ablation in 6 (43%) for pulmonary vein isolation. Median BMI was 27.2kg/m2 and left atrial volume (LAV) was 115.65 ml. LAEAT decreased from 35.47ml (28.6-53.9) to 19.37ml (11.48-30.65) post-ablation (p&lt;0.001) ( Panel C ), despite minimal BMI change (median change 0.5kg/m 2 , p=0.07) ( Panel D ). The reduction was higher in persistent AF patients compared to paroxysmal (35.61ml vs. 14.46ml, p=0.016). LAEAT reduction was correlated with pre-ablation LAV (r=0.675, p=0.008), LA fibrosis (r=0.82, p&lt;0.001), and BMI (r=0.815, p&lt;0.001); and post-ablation LAV (r=0.676, p=0.011), and BMI (r=0.798, p&lt;0.001). There was no correlation between LAEAT reduction and ablation-induced scarring. AF recurred in 9 patients (64.2%). Pre- and post-ablation LAEAT trended higher in those with recurrence compared to those without (42.72mL vs. 34.87ml, p=0.11 and 26.09ml vs. 13.85ml, p=0.11). LAEAT reduction relative to pre-ablation LAEAT was similar between groups. Conclusion: AF ablation was associated with a significant decrease in LAEAT. LAEAT did not affect ablation-induced scarring. The mechanisms and potential implications of these findings require further investigation.
Abstract 4142159: Impact of Tricuspid Regurgitation on Readmission Outcomes in Patients with Heart Failure – United States Population-Based Survey Analysis
Authors: Muhammad Yousuf, Noor Fatima, Muhammad Usman Almani
Journal: Circulation (2024)

Background: Tricuspid regurgitation (TR) is a common occurrence in patients with heart failure (HF), and its role in disease progression has gained attention in recent years. While TR can worsen the clinical outcomes in HF patients, its impact on gender, racial and socioeconomic factors remains largely unexplored. With growing evidence supporting the role of percutaneous interventions for the treatment of significant TR, understanding these disparities is more crucial than ever. Methods: Data was extracted from the National Readmission 2016 - 2020 Database. We used ICD-10 code I50 to identify the patients primarily admitted for HF and subdivided the cohort into two groups based on presence or absence of TR using the ICD-10 codes I36.1 and I07.1. We performed multivariable Poisson regression analysis to determine hazard ratio of 90-day HF-specific readmission in HF patients with and without TR. Subgroup analyses were performed based on (1) gender, (2) age, (3) insurance status, (4) location and teaching status of admitting hospital, and (5) patients’ household neighborhood income quartile. All the analyses were adjusted for age, gender, insurance status, Charlson co-morbidity index and hospital characteristics. STATA 16 software was used for the analysis. Results: Among 971,368 HF patients, 83987 (9.03%) patients without TR and 3988 (9.66%) patients with TR had a 90-day HF-specific readmission. HF patients with TR were 9% more likely to have HF-specific readmission in 90-days (HR: 1.09, 95% CI 1.03 – 1.15, p = 0.002). In the subgroup analysis, female patients (HR: 1.16, 95% CI 1.07 – 1.25, p &lt; 0.001), patients with age &gt; 40 years of age (HR: 1.09, 95% CI 1.03 – 1.15, p = 0.002), patients with Medicare insurance (HR: 1.09, 95% CI 1.03 – 1.16, p = 0.005), patients admitted to urban non-teaching (HR: 1.12, 95% CI 1.01 – 1.23, p = 0.024) and urban teaching hospitals (HR: 1.08, 95% CI 1.01 – 1.15, p = 0.027) and the patients belonging to the lowest (HR: 1.11, 95% CI 1.01 – 1.22, p = 0.026) and the highest household neighborhood income quartiles (HR: 1.23, 95% CI 1.08 – 1.40, p = 0.002) had higher risk of 90-day HF-specific readmission as shown in Figure 1. Conclusion: In our adjusted population-based survey analysis, we observed significant gender, socioeconomic and hospital-based disparities in readmission outcomes of HF patients with TR compared to those without TR.
Abstract 4142971: Lower Resilience is Associated with Increased Risk of Heart Failure Hospitalizations and Cardiovascular Death in High-Risk Heart Failure
Authors: Naba Farooqui, Kyle Steiger, Jill Killian, Jamie Smith, Margaret Redfield, Shannon Dunlay
Journal: Circulation (2024)

Introduction: Psychological resilience is the ability to adapt to significant adversity. Higher resilience has been associated with better quality of life in HF, but its association with outcomes is not known. Herein, we characterize resilience and its association with outcomes in HF. Research Questions/Hypothesis: Greater resilience is associated with better health status and outcomes in high-risk HF. Methods: In a prospective study, adult residents of 11 counties in Southeastern Minnesota with HF who had been hospitalized with decompensated HF or ventricular arrhythmia (“high-risk HF”) in the preceding 1 year were mailed a survey that included questionnaires to assess resilience (Connor Davidson resilience scale, CD-RISC2), health status (KCCQ-12), and other psychosocial constructs in March 2022. Patients were divided into tertiles by resilience scores, and association with outcomes (survival and hospitalization) were examined using Cox proportional hazard regression and Andersen-Gill models, respectively. Results: Among 649 respondents (mean age 76 ± 11.5 years, 40% women, 64.3% HFpEF), patients with greater resilience were older ( p=0.015 ), had lower BMI ( p=0.003 ) and were more often retired or employed (vs disabled or unemployed, p&lt;0.001 ). Greater resilience was moderately correlated with better health status (r=0.33), social support (r=0.27), and health literacy (r=-0.30); and lower treatment burden (r=-0.42), symptom burden (r=-0.41), and fewer depressive symptoms (r=-0.41) ( p&lt;0.001 for all ). At 1-year follow up, patients with the lowest resilience (lowest tertile) were at a significantly increased risk for HF hospitalizations (adjusted HR 2.09, 95% CI 1.06-4.11) and CV mortality (adjusted HR 1.90, 95% CI 1.01-2.57) compared to those with highest resilience. There was no statistically significant association of resilience with risks of all-cause mortality or all-cause hospitalizations after adjustment ( Figures 1A-D ). Conclusion: Higher resilience is associated with better health status and psychosocial profile. Patients with low resilience are at increased risk for HF hospitalizations and CV mortality. Impact of resilience on long term outcomes and response to interventions must be tested in future studies.
Abstract 4142104: Ischemic Stroke and TIA Incidence in Transcatheter Aortic Valve Replacement Versus Surgical Aortic Valve Replacement: A Comparative Systematic Review and Meta-analysis
Authors: Palak Patel, Vikash Kumar Karmani, Jaykumar Oza
Journal: Circulation (2024)

Objective: This systematic review and meta-analysis aimed to compare the incidence of ischemic stroke and Transient ischemic attack (TIA) post-transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) in intermediate or high surgical risk patients with aortic stenosis, as this assessment may influence the choice of intervention. Methods: In accordance with PRISMA guidelines, we conducted a comprehensive search of PubMed, Google Scholar, and Cochrane CENTRAL databases from inception to December 2023 to identify trials and observational studies comparing the incidence of stroke and TIA after 30 days and 1-year post-TAVR vs SAVR from their inception through December 2023. Odds ratios (ORs) with 95% confidence intervals (CIs) for each study, employing a random-effects model for data synthesis irrespective of heterogeneity, were utilized as measures of outcomes. Heterogeneity was assessed using I2 statistics. All statistical analyses were conducted using Review Manager (Rev Man, Version 5.4; The Cochrane Collaboration, Copenhagen, Denmark). Results: After screening of 4549 articles, eight randomized controlled trial studies consisting of 5 randomized controlled trials and three observational studies with a total of 6879 patients were included in this meta-analysis; six studies comparing 30-day stroke incidence, no significant difference was found between TAVR and SAVR (OR 0.83, 95% CI 0.59 to 1.17, p=0.30, I2 3%). Seven studies showed that TAVR patients had a similar 1-year stroke risk to SAVR patients (OR 0.92, 95% CI 0.64 to 1.33, p=0.67, I2 52%). In the TIA case, there was no evidence of a significant difference between TAVR and SAVR in the risk of having a transient ischemic attack within 30 days following surgery (OR 0.93, 95% CI 0.24 to 3.63, p=0.92, I2 52%), although There was a greater 1-year risk of having a transient ischemic attack in the TAVR group compared to the SAVR group, OR 1.15 (95% CI 0.72 to 1.82, p=0.56, I2 0%), however, this was not a statistically significant difference. Conclusion: Our meta-analysis showed no significant differences in either ischemic stroke or TIA occurrences within 30 days and 1-year post TAVR and post SAVR in intermediate or high surgical risk patients.
Abstract 4142969: Temporary Mechanical Circulatory Support Modulates Inflammation And Fibrosis In Cardiogenic Shock Patients Bridged To Cardiac Replacement.
Authors: Muthu Kumar Krishnamoorthi, Khush Patel, Arvind Bhimaraj
Journal: Circulation (2024)

Background: Temporary mechanical circulatory support devices (t-MCS) facilitate recovery of the patients, to then bridge them to cardiac replacement. A new paradigm of resting and recovering the heart with a t-MCS device is being explored. The understanding of mechanisms of recovery with t-MCS’s could facilitate the modulation of specific pathways to promote recovery. We compare the impact of two widely used t-MCS strategies in heart failure (HF): percutaneous left ventricular assist device (HFpVAD) vs Intra-aortic balloon pump (HFIABP) on the genetic landscape of the heart tissue in patients being bridged to cardiac replacement. Hypothesis Cardiac tissue of patients treated with pVAD will have distinct changes when compared to IABP supported hearts in relation to unsupported heart failure tissue. Methods: Myocardial tissue was collected at the time of surgery from 4 patients bridged with a pVAD (Impella 5.5) and 4 bridged with IABP. Tissues from patients who were bridged without MCS were used as HF tissues. Bulk RNA paired-end sequencing of cardiac tissues was performed on an Illumina Hiseq 4000 was performed. StringTie was used to perform expression levels for mRNAs. Results: Gene ontology (GO) analysis of the differentially expressed genes (DEG) resulted in GO terms such as extracellular matrix, cytokine activity, and adaptive immune response indicated that most of the DEG were contributing to the regulation of fibrosis and inflammation related functions. KEGG analysis of the DEG resulted in pathway terms such as malaria, complement and coagulation cascades, ECM receptor interaction, and cell adhesion molecules. Interestingly, the predominance of ECM/fibrosis-related pathways and infection/immune system pathways in both GO and KEGG analysis signals the involvement of these pathways in the t-MCS assisted resting of the cardiac tissue in patients with cardiogenic shock. Conclusion: Our results illustrate that t-MCS in general modulates fibrosis and inflammation related genes with unloading with p-VAD having distinct changes with more genes when compared to IABP support. Further studies exploring these mechanisms could discover a therapeutic focus for promoting t-MCS assisted myocardial recovery.
Abstract 4143048: Role of Inflammatory Cytokines in Triggering Ventricular Arrhythmias in Pulmonary Hypertension
Authors: Peter Bronk, Peng Zhang, Eric Wang, Glenn Radice, Cao Tran, Gaurav Choudhary, Bum-rak Choi
Journal: Circulation (2024)

Introduction: Pulmonary hypertension (PH) is a deadly disease, and the corresponding survival rates are estimated at 50% over 5 years. Most patients with severe PH die of right heart failure or sudden cardiac death from arrhythmias. There are strong indications supporting inflammation as a major proarrhythmic factor in PH. Goal: To investigate whether and how inflammatory cytokines promote cardiac arrhythmias in PH rat model. Methods: We used rat models of PH: 1) decompensated PH using Su5416 injection (SU) and 3 weeks of hypoxia (Hx) (Su/Hx, n=7), 2) compensated PH using Hx alone (n=3), 3) sham control (CTR, n=8). Interleukin 1b (IL-1b) and IL-18 were perfused (5 ng/ml for 90 min) and action potentials (AP) were mapped using optical mapping with voltage sensitive dye. Results: APDs in the right ventricle (RV) were significantly increased in Su/Hx (86±9 ms, p=0.014) vs. Hx (75±10 ms) and CTR (74±8 ms). APD dispersion is also increased in Su/Hx (23±3 ms, p=0.011) vs. Hx (8±3 ms) and CTR (9±4 ms), leading to conduction block and reentry formation around RVOT in Su/Hx during S1S2 programmed stimulation (Fig-A). Longitudinal conduction velocity (CV) is significantly slower in Su/Hx (0.58±0.08 m/s, p=0.01) vs. Hx (0.78±0.12 m/s) and CTR (0.84±0.10 m/s). Perfusion of IL-1b/IL-18 significantly prolongs APDs in the Su/Hx model (Fig-B, APD=109±19 ms, p=0.003) but not in Hx (78±13 ms) and CTR (83±7 ms), associated with frequent PVCs in Su/Hx model (Fig-C.D, n=5/7 hearts in Su/Hx vs. 0/3 in Hx only and 2/8 hearts in CTR), indicating that inflammatory cytokines increase arrhythmia risks in decompensated PH. Conclusion: More severe form of PH (Su/Hx) showed the highest arrhythmia risks compared to the compensated PH model (Hx) and control under IL-1b/IL-18 perfusion, supporting the idea that inflammation in PH may play key roles promoting electrical remodeling and arrhythmias.