tbuckley/cabot-search huggingface dataset:
Abstract 4141439: Catheter ablation and clinical outcomes among older Medicare beneficiaries with atrial fibrillation
Authors: Benjumin Hsu, Dae Kim
Journal: Circulation (2024)

Background: Catheter ablation (CA) is increasingly used for treatment of atrial fibrillation (AF). However, CA has not been widely adopted in the older population with AF. The aim of this study is to examine the risks of adverse outcomes following CA in older people with AF. Methods: Using 2014-2019 Medicare claims, we conducted a propensity score analysis of patients treated with CA within 6 months of new AF diagnosis to patients treated with only antiarrhythmic therapy in the 6-month period. The outcome follow-up began after the 6-month period. Cox proportional hazards models were used to estimate hazard ratios (HR) for the composite and individual endpoints from CABANA trial (death, stroke, major bleeding or cardiac arrest) and CASTLE-AF trial (death or heart failure). Subgroup analyses were performed by sex, race-ethnicity, social deprivation index, frailty and dementia. Results: The study population comprised of 14623 AF patients (mean age, 76.1±7.6 years; 55% female, 28% frailty, 13% dementia), including 8% receiving CA. The mean follow-up was 1.8 years. Compared to patients with only antiarrhythmic therapy, patients treated with CA had lower rates of CABANA endpoints (CA vs antiarrhythmic therapy: 5.6 vs 11.7 per 100 person-years; HR:0.72, 95%CI:0.66-0.77) and CASTLE-AF endpoints (6.5 vs 13.8 per 100 person-years; HR:0.72, 95%CI:0.67-0.78). The benefits of CA were consistent in both female and male for CABANA endpoints (female: HR:0.71, 95%CI:0.64-0.79 and male: HR:0.72, 95%CI:0.65-0.81) and CASTLE-AF endpoints (female: HR:0.65, 95%CI:0.59-0.73 and male: HR:0.78, 95%CI:0.71-0.87), and in both frail and non-frail patients for CABANA endpoints (frail: HR:0.72, 95%CI:0.66-0.80 and non-frail: HR:0.70, 95%CI:0.63-0.77) and CASTLE-AF endpoints (frail: HR:0.89, 95%CI:0.81-0.97 and non-frail: HR:0.69, 95%CI:0.63-0.75). Similar trends were observed for subgroups defined by race-ethnicity, social deprivation index, and dementia. Conclusions: These findings suggest that CA may be beneficial for older AF patients. Nonetheless, further investigation of the safety and efficacy of CA given to older patients in well-designed interventional trials are warranted.
Abstract 4147614: Prevalence and Impact of Stroke In Young (18-44 Years) ACHD-Related Admissions by Median Household Income Quartiles: A 2019 National Inpatient Sample Analysis
Authors: Pavana Appala, Nikhila Appala, Prerna Bansal, Vidhi Khanolkar, Ammara Ghaffar, Maneeth Mylavarapu, Rupak Desai
Journal: Circulation (2024)

Background: The risk of stroke in Adult Congenital Heart Disease (ACHD) is well established. However, the prevalence and impact of stroke in young ACHD-related admissions stratified by median household income remain underexplored. Methods: The National Inpatient Sample (2019) was utilized to identify the rate of stroke admissions among young (18-44 years) ACHD patients. We also evaluated comorbidities and outcomes (all-cause mortality [ACM], length of stay [LOS], disposition,&amp;charges) based on the median household income quartiles and compared two cohorts of lowest (0-25th percentile) and highest (75-100thpercentile) median household income (LMHI vs HMHI). Results: Of 41950 young (18-44 years) ACHD patients, 5360 patients had stroke (12.8%). Patients in the LMHI group were relatively older (median age 36 years vs 35 years) and had a greater proportion of males (53.8% vs 46.0%) when compared to patients in the HMHI group. Patients admitted with stroke were of greater proportion in the LMHI group (13.2% vs 12.1%) compared to the HMHI group. Comorbidities like alcohol abuse (4.7% vs. 2.3%), depression (9.8% vs. 7.0%), hypertension (13.0% vs. 5.6%), obesity (21.2% vs. 18%), drug abuse (12.3% vs 4.2%), and tobacco use disorder (30.4% vs 11.2%) were higher for LMHI when compared to HMHI. Regarding in-hospital outcomes, ACM (3.7 vs. 1.9%) and discharge to home (71.6 vs. 66.5) were higher with HMHI, whereas the LMHI cohort demonstrated fewer routine discharges, higher transfers to other facilities, and prolonged LOS (5 vs. 3 days, p&lt;0.001). When adjusted for confounders, there were statistically higher odds of AIS in ACHD patients from the LMHI group vs. the HMHI group [aOR 1.33; 1.02-1.74; p=0.045]. However, no association of income quartile with overall stroke risk was observed. Conclusion: The prevalence of stroke is significantly higher in the LMHI group. When controlled for confounders, there was a higher risk of AIS without any impact on overall stroke. Furthermore, the lowermost income quartile was associated with fewer routine dispositions, and frequent transfers can further adversely increase healthcare inequalities and healthcare costs.
Abstract 4147602: The Paradox Role of Sirtuin 6 In Coronary Microvascular Function under Metabolic Stress
Authors: Yang Wang, Molly Enrick, James Gadd, Blessing Nagy, Iyanuoluwa Ogunmiluyi, Liya Yin
Journal: Circulation (2024)

Coronary microvascular dysfunction (CMD), which is associated with diabetic cardiomyopathy, Takotsubo cardiomyopathy, andheart failure with preserved ejection fraction (HFpEF), is understudied. CMD is characterized by impaired endothelial-dependent vasodilation, but detailed mechanisms have yet to be elucidated. Nuclear Sirtuin 6 (SIRT6) plays essential roles in gene transcriptional, stress tolerance, DNA repair, inflammation, and aging. SIRT6 is strongly associated with cardiovascular pathologies, but how SIRT6 regulates endothelial metabolisms and homeostasis under metabolic stress and the underlying mechanism remains poorly understood. It might be because global Sirt6 knockout mice are perinatally lethal caused by hypoglycemia, suggesting the essential role of SIRT6 in glucose metabolism. In our preliminary studies, we generated inducible global Sirt6 knockout mice by crossing with Sirt6 f/f mice with CAG-cre (Sirt6 f/f, CAG ), and mice were viable with normal glucose levels. However, they showed impaired endothelial-dependent dilation (EDD) and impaired coronary flow reserve (CFR), an index clinically used to diagnose CMD. It suggests that deletion of Sirt6 might cause EC dysfunction because Sirt6 is reported to protect EC from premature senescence and oxidative stress by sustaining high eNOS levels. Surprisingly, when we studied non-inducible Sirt6 endothelial-specific knockout (Sirt6 f/f, tie-2 cre ) and inducible Sirt6 endothelial-specific knockout (Sirt6 f/f, Cdh5-cre/ERT2 ) and wild-type (WT) mice, Sirt6 f/f, Tie-2 and Sirt6 f/f, Cadh5 mice do not phenocopy the inducible global SIRT6 knockout mice, they had normal EDD and CFR. When the mice were fed a high fat and high sugar (HFHS) diet, the Sirt6 f/f, Tie-2 and Sirt6 f/f, Cadh5 had impaired EDD, suggesting Sirt 6 functioned differently in the mice fed with chow diet or HFHS diet. We hypothesize Sirt 6 deficiency causes coronary endothelial dysfunction and contributes to CMD; activating Sirt6 will ameliorate CMD. EDD was assessed using myography (DMT). Myocardial blood flow (MBF) was measured by Doppler. Our preliminary data show that the mediator of coronary vasodilation switched from NO to H 2 O 2 in the Sirt6 knockout mice with impaired EDD. Interestingly, when the mice fed on HFHS were treated with Sirt 6 activator MDL-800, the coronary microvascular function was improved, and the blood glucose level was decreased. The underlying mechanism and the pathways involved will be elucidated.
Abstract 4116486: Association of assessment of clinical congestion in patients with heart failure compared with assessment using bioimpedance and microwave spectroscopy
Authors: Agata Bielecka-Dabrowa, Ilona Zasada, Wielislaw Olejniczak, Agata Sakowicz, Maciej Slot
Journal: Circulation (2024)

Background: Physicians have to find a balance between decongestion therapy and the risk of dehydration so non-invasive methods assessing congestion are of great importance. Purpose: The study aimed to compare the clinical assessment of congestion to bioimpedance and microwave spectroscopy. Methods: 27 hospitalized HF patients with congestion (40% females) (Congestion Group) and 59 HF patients without fluid overload (66% females) (NON-Congestion Group) were included. Clinical examination, chest x-ray, laboratory results, echocardiography, non-invasive body mass analysis (Tanita Pro), NT-poBNP, and selected modern biomarkers concentrations [GDF-15, galectin-3, FABP, copeptin, VEGF were performed. Additionally, we assessed pulmonary congestion using a proprietary sensor with a microwave spectroscopy method based on analyzing the dielectric properties of an object (patent applications P.442466). Results: There were no differences in body mass index, blood pressure values, left ventricular ejection fraction (LVEF), and echocardiographic parameters of diastolic left ventricular function between groups. In the Congestion Group, we observed significantly more patients in NYHA Class 3 and 4 (p&lt;0.001), lower values of fT3 (median 2.4 vs 2.7; p=0.02), higher a FIB-4 index (p=0.04), lower GFR MDRD (median 52.7 vs 66.7;p=0.04), higher concentrations of: NT-proBNP (pg/ml) (median 545 vs 101; p&lt;0.001), galectin-3 (ng/ml) (median 15.01 vs 11.35; p=0.01), GDF-15 (pg/ml) (median 2069.27 vs 734.64; p=0.01), FABP (pg/ml) (median 293.6 vs 101; p=0.008) compared to NON-Congestion Group, and a larger number of detected congestion in chest x-ray (p&lt;0.01) and more patients with limb edema (p= 0.0037). The patients with congestion also needed longer hospitalizations (p=0.008). Patients with congestion had lower total body water content in kg and intracellular water (ICW) (kg) (p=0.02 and p=0.01, respectively), and the higher extracellular water/total body water index (ECW/TBW) (p=0.001) assessed in bioimpedance and significantly higher Absorption Loss evaluated with the use of microwave spectroscopy (p=0.02). In a multiple logistic regression model, the factor that was independently associated with clinically diagnosed congestion was NT-proBNP &gt;1095 pg/ml (OR 111.6, 95% CI: 2.6-50.6; p=0.001) (Figure 1). Conclusions: Absorption Loss and ECW/TBW are valuable new diagnostic tools in diagnosing lung congestion in patients with heart failure.
Abstract 4146311: Cardiac Thickening, Cell Free DNA, and Rejection in the 2 <sup>nd</sup> Porcine Cardiac Xenograft
Authors: Andrew Tully, Muhammad Mohiuddin, Javier Galindo, Sarah Cipriano, Kapil Saharia, Allison Lankford, Timm Dickfeld, Sadegh Asadi, Albert Hicks, Susie Hong-Zohlman, Anuj Gupta, Alison Grazioli, Erika Feller, Bartley Griffith, Manjula Ananthram
Journal: Circulation (2024)

Introduction/Background: A 58-year-old man with inotrope dependent heart failure was declined for allotransplant and MCS at multiple centers and was transplanted with a 10 gene-edited porcine cardiac xenograft under FDA expanded access Investigational New Drug (eIND) approval. After requiring perioperative transfusions, by post operative day (POD) 13, endomyocardial biopsy revealed antibody and complement deposition without damage or cellular infiltrate. Hemodynamic decompensation on POD 29 prompted biopsy revealing antibody mediated rejection (AMR). The patient required ECMO support POD31 and chose comfort care POD 40. Research Questions/Hypothesis: The cardiac xenograft doubled in mass from implant to autopsy. Donor derived cell free DNA (cfDNA) correlated temporally with the rejection findings. These processes are hypothesized to correlate. Approach: Routine TTE measurements of diastolic LV posterior wall dimension (LVPWd), intraventricular septal dimension (IVSd), LV mass, and LV mass index were taken. Donor derived cfDNA was measured weekly and PRN (Care Dx Inc., Brisbane, CA). Pearson correlation coefficient analysis was conducted in GraphPad Prism 10 (Dotmatics, Boston, MA). Results/Data: POD 26 TTE measurements indicated thickening graft. POD 30 cfDNA began elevating. cfDNA correlated moderately with LVPWd (r = 0.43, p=0.4) and IVSd (r= 0.5, p=0.31) less so with LV mass (r= 0.28, p=0.59) and LV mass index (r=0.34, p=0.51) Conclusions: Xenograft cardiac thickening measured on TTE preceded elevation in cfDNA. Both were moderately correlated and temporally corresponded to biopsy diagnosed AMR and ultimate graft failure. Future xenograft surveillance will likely benefit from multimodal approach.
Abstract 4140102: Changes in EQ-5D-5L with Aficamten in Obstructive Hypertrophic Cardiomyopathy (oHCM): the SEQUOIA-HCM Trial
Authors: Christian Schulze, Theodore Abraham, Roberto Barriales-Villa, Brian Claggett, Caroline Coats, Pablo Garcia-Pavia, Albert Hagege, James Januzzi, Ian Kulac, Raymond Kwong, Martin maron, Ahmad Masri, Michael Nassif, Iacopo Olivotto, John Spertus, Josef Veselka, Michael Butzner, Stephen Heitner, Daniel Jacoby, Stuart Kupfer, Fady Malik, Lixin Meng, Sanatan Shreay, Amy Wohltman, Mathew Maurer
Journal: Circulation (2024)

Introduction: In patients with obstructive hypertrophic cardiomyopathy (oHCM), the SEQUOIA-HCM trial demonstrated that aficamten, a next-in-class cardiac myosin inhibitor, improved exercise capacity, heart failure symptoms and hemodynamics compared with placebo. Aficamten’s impact on overall quality-of-life (QoL) in oHCM has not been reported. Hypothesis: Aficamten, compared with placebo, improves QoL as assessed by the EQ-5D-5L. Aims: To describe EQ-5D-5L changes in patients enrolled in SEQUOIA-HCM. Methods: SEQUOIA-HCM (NCT05186818) is a phase III, placebo-controlled trial of adults with symptomatic oHCM randomized to aficamten (n=142) or placebo (n=140) on top of standard-of-care medical therapy. Participants underwent blinded dose escalation over 6 weeks and were treated for 24 weeks followed by a 4-week washout. EQ-5D-5L (ranges from 0 to 1) and overall QoL using the Visual Analogue Scale (VAS; from 0 to 100) was measured at baseline through week 28 with higher scores indicating better QoL. Aficamten treatment effect on EQ-5D-5L was estimated using linear regression (study visits) and mixed effects regression (overall treatment effect) using all follow-up data with model adjustments for baseline EQ-5D-5L score and randomization stratification variables. Results: Mean age (n=282) was 59.1±12.9 years (40.8% women; 79.1% white). Aficamten baseline EQ-5D-5L index and VAS scores were 0.8±0.19 and 71.2±17.9 (placebo: 0.78±0.2; 68.9±18.6), respectively. Aficamten improved the EQ-5D-5L by 0.026 (95% CI: -0.001, 0.052; p=0.056) and the VAS by 2.8 points (95% CI: 0.8, 4.8; p=0.006) versus placebo with significant differences as early as 8 weeks after treatment initiation (p=0.005). After treatment withdrawal at 24 weeks, QoL benefits in aficamten-treated patients decreased compared with placebo (Figure: Index, p&lt;0.001; VAS, p=0.003), with hemodynamic parameters returning to baseline. Conclusions: Aficamten yielded early, sustained and significant improvement in overall QoL compared with placebo. Withdrawal of aficamten was associated with the loss of treatment benefits and perhaps an increased perception of pre-treatment symptoms. These data support a role of aficamten in improving QoL among patients with oHCM.
Abstract 4147644: Regional Distribution and Overlap of Left Atrial Epicardial Adipose Tissue and Fibrosis
Authors: Ahmad Kassar, Aashild Telle, Yaacoub Chahine, Nadia Chamoun, Patrick Boyle, Nazem Akoum
Journal: Circulation (2024)

Background: Left atrial epicardial adipose tissue (LA-EAT) and fibrosis are implicated in the pathophysiology of the atrial fibrillation (AF) substrate. Hypothesis: The distribution of fibrosis and LA-EAT differs across various regions of the LA. Aims: Ascertain whether high fibrosis regions coincide with high EAT regions. Identify specific anatomical regions in which LA-EAT and fibrosis tend to co-localize. Methods: LA-EAT was imaged using MRI Dixon sequences and images were segmented axially using the software contouring tools. LGE-MRI was used for LA fibrosis quantification and segmentation. The regions of fibrosis and fat were then co-registered with the atrial geometry and projected onto the left atrial shell. A universal atrial coordinates (UAC) approach was then used to systematically delineate anatomical LA regions in a manner independent of inter-individual variabilities in scale and shape. Specifically, the LA was divided into 10 regions (left and right versions of: posterior-inferior, posterior-superior, roof, anterior-superior, and anterior-inferior). Levene’s test and ANOVA were used to check for any statistically significant variability. Results: Nineteen patients were recruited (94% male; median age 72[62-74]; BMI 32.1±6.3; LA volume index 71.0±21.5mL/m 2 ).LA fibrosis was highest in the left posterior superior segment, right anterior inferior, and left posterior inferior (39.3±16.2%,34.7±26.8%, and 25.7±20.9% respectively;F=1.9,p=0.15). LA-EAT was most prominent in the right anterior superior, left posterior inferior, and left anterior inferior segments (38.1±25.3%,35.6±18.4%,and 33.1±18.9% respectively; F=0.94, p= 0.39). Spatial co-localization of fat and fibrosis was highest in the left posterior inferior region (8.95±2.1%), followed by the left posterior superior, right anterior superior, and left anterior inferior region (7.9±2.1%,7.2±1.7%,and 6.3±1.6% respectively; F= 0.29, p=0.83 ). Conclusion: LA fibrosis and EAT have differing regional preponderances, impacting the AF substrate through infiltrative and paracrine effects. This fibro-fatty remodeling creates structural and conduction abnormalities, forming stable reentrant circuits and perpetuating AF by providing varied pathways and refractory periods.
Abstract 4141446: Sodium Glucose Co-transporter 2 (SGLT2) Inhibitors Promote Resiliency to High Pressure Stress in the Human Microvasculature
Authors: Gopika SenthilKumar, Julie Freed, Katie Cohen
Journal: Circulation (2024)

Emerging evidence suggests that vascular stress from cardiovascular-related co-morbidities promotes microvascular dysfunction, a key component in the development of heart failure with preserved ejection fraction. The sodium glucose co-transporter 2 (SGLT2) inhibitor empagliflozin has been shown to reduce both morbidity and mortality associated with heart failure with preserved ejection fraction, however the full scope of influence of this therapy on human microvascular function remains unknown. We hypothesized that pre-treatment of isolated human microvessels with empagliflozin will prevent stress-induced endothelial dysfunction as evidenced by preserving both the magnitude of flow-induced dilation (FID) as well as the ability to dilate to nitric oxide. Human resistance arterioles (80-250µm) from healthy adults (defined as patients with ≤1 risk factor for cardiovascular disease) were dissected from discarded surgical adipose tissue and treated with empagliflozin (1µM), or vehicle control (ethanol) for 16-20 hours prior to the flow experiment. Vessels were cannulated for videomicroscopy and subjected to high intraluminal pressure (150mmHg, 30 min), an acute stress known to induce endothelial dysfunction. Vessels were pre-constricted with endothelin-1 prior to initiation of flow. A nonlinear logistic regression was used to determine differences between curves. Compared to vehicle control, vessels pre-treated with empagliflozin (1µM ) exhibited nitric oxide-dependent FID as dilation was impaired in the presence of the nitric oxide synthase inhibitor L-NAME (EC50 Control: 10.7 vs L-NAME 83.45, p=0.0107). This data suggests that empagliflozin, an SGLT2 inhibitor, promotes microvascular resilience to stress via preservation of nitric oxide-mediated FID. The ability to elicit stress resilience may explain in part some of the cardiovascular benefits associated with SGLT2 inhibitors and may offer unique opportunities for early intervention or prevention of microvascular dysfunction associated with comorbidities that contribute to heart failure with preserved ejection fraction.
Abstract 4140142: Neighborhood Perceptions Associate with Lipid Biomarkers in African-American Women with Cardiovascular-Kidney-Metabolic Syndrome: Data from the Step It Up Digital Health-Enabled, Community-Engaged Physical Activity Intervention
Authors: Sandy Reynolds, Marcus Andrews, Yvonne Baumer, Dana Sandler, Sonal Sharda, Shelby Hicks, Elizabeth Aquino Peterson, Fnu Abhinav Saurabh, Manuel Cintron, Mario Pita, Hannatu Tarfa, Ayushi Dave, Foster Osei Baah, Colby Ayers, Laurel Mendelsohnl, Sarah Deguzman, Azeb Redai, Marie Marah, Ayanna Wells, Katherine Tolentino, Maureen Sampson, Alan Remaley, Tiffany Powell-Wiley
Journal: Circulation (2024)

Background: Cardiovascular-kidney metabolic (CKM) syndrome is exacerbated among individuals experiencing chronic exposure to both environmental and psychosocial stressors. Both neighborhood and individual-level stressors increase chronic inflammation resulting in worsened CKM factors, such as hypertension, diabetes, and dys/hyperlipidemia. However, associations between neighborhood perceptions (NP) and lipid profiles remain understudied. Therefore, we examined associations between NP domains and lipid profiles among African-American (AA) women with ≥Stage 1 CKM syndrome (overweight/obesity) residing in resource-limited neighborhoods within the Washington, DC area. Methods: Participants were enrolled in Step It Up, a technology-enabled, community-engaged physical activity (PA) intervention. Fasting blood samples were drawn at baseline to measure lipoproteins using Nuclear Magnetic Resonance (NMR) spectroscopy. Factor analysis of overall NP identified four perception sub-scores: disorder, social cohesion, violence, and safety (higher score=favorable perception). Associations between NP domains and lipoprotein particles were analyzed using multivariable regression adjusting for BMI, ASCVD 10-year risk score, and lipid-lowering therapy. Results: Participants (n=169) had mean age=57.16 ± 12.00 and BMI 35.99 ± 6.57. Perceptions of safety were positively associated with LDL concentrations (LDLc) and large LDL particles (L-LDLp) (β=4.70 [SD=2.41], p=0.05, β= 43.75 [17.70], p= 0.01), respectively). Perceptions about neighborhood violence were positively associated with L-LDLp (marginally) and very-low-density lipoprotein size (VLDLz) (β= 7.10 [3.96], p=0.08, β= 0.31 [0.14], p= 0.02, respectively). No associations were found between disorder and social cohesion with lipid biomarkers. Conclusions: After adjusting for BMI, ASCVD risk, and lipid-lowering therapy, there were significant associations between neighborhood perceptions of safety and violence with lipid profiles among AA women with CKM syndrome. Greater perceived safety was associated with higher LDLc and L-LDLp while more favorable perception about neighborhood violence was associated with higher L-LDLp. Future work should examine whether improving neighborhood resources and perceptions may improve CKM health among urban AA women.