tbuckley/cabot-search huggingface dataset:
Abstract 4122780: Muscle Quality Defines Sarcopenic Obesity in Older Adults In Association with Cardiac Function
Authors: Sarah Tan, JIE JUN WONG, Glades Tan, Ru Tan, Fei Gao, Loon Yee Teo, See Hooi Ewe, Wee Shiong Lim, Hong Chang Tan, Angela Koh
Journal: Circulation (2024)

Background: Obesity phenotypes are increasingly used to define cardiovascular diseases (CVD) risks. Age-related deteriorations in skeletal muscle function have ignited interest in the co-occurrence of sarcopenia and obesity in older adults. However, the traditional definition of sarcopenia (low appendicular skeletal mass [ASM] and handgrip strength [HGS]) may lead to underdiagnosis of sarcopenic obesity (SO) in overweight individuals (due to higher muscle mass). To address this enigma, we evaluated the use of muscle quality (MQ), as an alternative metric for SO, in association with cardiac function. Methods: Community older adults without CVD were prospectively annotated for skeletal mass, HGS and cardiac function via bioimpedance analysis, dynamometer, and simultaneous acquisition of echocardiography respectively. Sarcopenia was defined by low ASM and low HGS. Low MQ (HGS divided by upper body ASM) was defined by males&lt;5.76kg/kg and females&lt;5.475kg/kg. Aerobic capacity (VO2 max,ml/kg/min) was computed by a physical activity prediction model. Mitral early diastolic inflow velocity to early diastolic annular tissue velocity (E/e’) and early to late diastolic inflow velocity (E/A) ratios were recorded. Results: Overall, low MQ was prevalent (34.3%) in n=574 participants (59% females), but only 17.4% fulfilled sarcopenia diagnosis. Higher BMI correlated with higher ASM but lower MQ (Fig 1). Low MQ prevalence was higher in the obese compared to the non-obese (64.7% vs 30.2%, p&lt;0.0001). Low MQ group was significantly older (69.0±10.4 vs 64.8±14.0 years, p&lt;0.0001), had higher prevalence of dyslipidemia (49.2% vs 40.9% p=0.002) and hypertension (45.2% vs 39.3% p&lt;0.0001) than the normal MQ group. The low MQ group had greater left ventricular mass (129±45 vs 114±44, grams, p&lt;0.0001), left atrial volumes (37±14 vs 33±13, ml, p=0.001), and demonstrated a greater degree of diastolic dysfunction (lower E/A (0.89±0.28 vs 1.1±0.49, p&lt;0.0001 and higher E/e’(8.63±2.42 vs 8.00±2.58, p=0.005), compared to the high MQ. VO2 max was lower in low MQ group (33±5.7 vs 36±6.7, p&lt;0.0001). By regression, low MQ was associated with E/A (β=-0.119, adjusted p&lt;0.0001) and VO2 max (β=-0.137, p&lt;0.0001) (Table 1). Conclusion: Muscle quality is a useful metric of muscle function for sarcopenia in obese older adults. The associations between low MQ with diastolic dysfunction and reduced aerobic capacity corroborate the clinical impact of MQ as a defining metric of sarcopenia in obesity.
Abstract 4122677: Reduced Costs and Readmissions With Outpatient Versus Inpatient Diuresis in Heart Failure Patients at UNC Hospital
Authors: Sonum Tharwani, Alexandra Leamy, Emily Baker, Grayson Eubanks, Mason Sanders, Carrie Neal, Sarah Waters, Thelsa Weickert
Journal: Circulation (2024)

Background: Heart failure (HF) remains a leading cause of hospital admissions, with high morbidity, mortality, and projected healthcare costs of $70 billion by 2030. Effective management of the patient’s volume status is crucial in managing symptom burden, preventing rehospitalization, and thus reducing healthcare expenses. In 2017, UNC Hospital opened an ambulatory diuresis clinic to address this issue. Aim: This retrospective cohort study evaluates the cost and rehospitalization rates of HF patients treated in the ambulatory diuresis clinic versus those receiving inpatient diuresis at the hospital. Methods: We retrospectively analyzed 2,950 unique HF patients from August 2017 to September 2023, treated with IV diuresis at UNC Hospital or its outpatient clinic. Patients were classified into a clinic cohort, who visited the diuresis clinic at least once, and a non-clinic cohort, who never visited and were defined by a primary HF diagnosis with an ED/observation visit or inpatient stay ≤ two days. The primary outcome measured was average readmissions per cohort; the secondary outcome included total charges from billing records. Rehospitalization and mortality rates were tracked via EHR. Statistical analyses, including descriptive and inferential statistics, were conducted to compare costs and outcomes between the two groups. Results: This study compared 996 patients in the clinic group with 1,954 in the non-clinic group, noting similar baseline characteristics of average ages of 66.80 and 67.24 years, BMIs of 33.95 and 33.73 kg/m^2, and one-year all-cause mortality rates of 21.18% and 22.77%, respectively. Average admissions per cohort were higher for the clinic group one year prior to the index visit—0.159 vs. 0.127—but decreased post-index visit: by six months, admissions were 0.094 for the clinic and 0.161 for the non-clinic; at one year, they were 0.133 and 0.210, respectively. Financially, the clinic group incurred $7,895 less in charges during the index visit and had lower total costs one-year post-index, at $17,785 compared to $23,982 for the non-clinic group. Conclusions: The study demonstrates that outpatient diuresis at UNC Hospital is more cost-effective than inpatient diuresis for HF patients and reduces rehospitalization rates at six months and one-year post-index visit. These results suggest that outpatient diuresis is cost-effective, may enhance patient outcomes, and could alleviate the strain on healthcare resources.
Abstract 4113188: Increased Physical Activity Intensity Associated with Reduced Risk of Atrial Fibrillation among Older Adults in South Korea: A Retrospective Cohort Study
Authors: Sun Jae Park, Hye Jun Kim, Minseo Kim, Jihun Song, Seogsong Jeong, Sang Min Park
Journal: Circulation (2024)

Introduction: Physical activity (PA) may be associated with a lower risk of atrial fibrillation (AF), but this relationship remains controversial. In particular, further research is needed on the association between changes in PA intensity and AF risk among older adults. Hypothesis: We hypothesized that an increase in PA intensity would be associated with a reduced risk of AF among older adults aged 65 years and older in South Korea. Aim: This cohort study aimed to evaluate the association between changes in metabolic equivalent tasks (METs)-min/week and the risk of AF in the elderly using a nationally representative database. Methods: We conducted a retrospective cohort study using the Korea National Health Insurance Service (KNHIS) database. This cohort included 1,726,697 individuals aged 65 years and older without a history of cardiovascular disease diagnosis who underwent two consecutive health screening examinations from 2009 to 2012. PA was defined as MET-min/week derived from two consecutive health examinations during 2009-2010 (1st period) and 2011-2012 (2nd period), respectively. The primary outcome was an AF diagnosis during the follow-up period from 2013 to 2021. We estimated the sub-distribution hazard ratio (sHR) and 95% confidence interval (CI) for the association of changes in PA intensity with AF using Fine-Gray sub-distribution hazard models after adjustment for covariates. Results: This study included 1,726,697 participants (mean age 71.08; 46.78% male). An increase in PA intensity was associated with a reduced risk of AF (P for trend&lt;0.001). Compared to persisting in physical inactivity, a change in PA intensity from physically inactive to ≥1000 MET–min/week was associated with a lower risk of AF (sHR, 0.83, 95% CI, 0.81-0.85). In contrast, a change in PA intensity from ≥1000 MET–min/week to being physically inactive was associated with a higher risk of AF (sHR, 1.30, 95% CI, 1.27-1.33) as compared to persistence in ≥1000 MET–min/week of PA intensity. Conclusions: An increase in MET-min/week may be associated with a reduced risk of AF among adults aged 65 years and older. Therefore, interventions encouraging PA should be recommended to maximize the health benefits of AF prevention in the elderly.
Abstract 4115027: Transcutaneous phototherapy improves left ventricular systolic function
Authors: James Kneller, Joe Nuttall
Journal: Circulation (2024)

Background: The emerging field of cardiac optogenetics uses pulses of light to stimulate optically-sensitive proteins in the heart, influencing cellular physiology with unprecedented spatiotemporal resolution. Potential benefits may include heart rhythm stabilization and relief from congestive heart failure (CHF). Transcutaneous phototherapy devices (LifeWave Inc, San Diego, USA) may provide similar benefit without the need for opsin expression in the heart or exogenous light sources. Objective: To investigate whether upregulation of carnosine activity using a wearable cutaneous phototherapy device may improve echocardiographic measures of left ventricular systolic function. Methods: The Carnosine ® adhesive skin patch (34 mm diameter) contain an organic crystalline material that reflects specific frequencies of infra-red light emitted through the skin, and known to activate carnosine dipeptides throughout the body. These function as a high-energy phosphate system known to enhance muscle function. Study participants (n=12 healthy volunteers, 40-66 years of age) underwent a focused baseline echocardiogram, which included atrial (A) and early (E) mitral valve inflow, peak tissue velocity (E’) at both the lateral and septal mitral annulus, and left ventricular ejection fraction (LVEF). 10-12 patches were then applied along the sternum and across the left thorax (3 rd -5 th interspace), incorporating the anterior axilla. The echocardiogram was repeated after 20-30 minutes. Results: LVEF was improved following application of the phototherapy device, increasing from 59.4±5.8% to 66.65±5.8% (Δ 6.3%, p&lt;0.05), predicting an improvement in overall cardiac function. In those with normal diastolic function at baseline, septal E’ increased 7.3±0.57 cm/s to 8.2±0.58 cm/s (Δ 0.87 cm/s, p&lt;0.05), indicating a direct effect on contractility. E and A wave velocities increased 2.46±0.14 cm/s and by 5.7±0.72 cm/s, indicating augmented hemodynamics trending towards significance. Conclusion: Cutaneous phototherapy devices may enhance left ventricular systolic function without the need for drug delivery, gene manipulation, or exogenous light sources.
Abstract 4114694: A Large Animal Model of Persistent Atrial Fibrillation
Authors: Pouria Mostafizi, Eli Lefkowitz, Jacob Ref, Sherry Daugherty, Adrian Grijalva, Kyle Eric Cook, Ike Chinyere, Jordan Lancaster, Jen Koevary, Steven Goldman, Talal Moukabary
Journal: Circulation (2024)

Purpose: Persistent atrial fibrillation (AFib), the most common sustained cardiac arrhythmia in the United States, poses substantial health hazards, such as the formation of blood clots, stroke, and heart failure. Despite available therapies such as ablation and antiarrhythmic drugs, there still is no definitive cure for AFib. Our study aims to bridge this gap by investigating the genetic and molecular factors underlying AFib through the development of an AFib model using Yucatan mini swine as the medium that closely mimics human cardiac physiology. Methods: We selected Yucátan mini swine as animal models because they closely resemble humans physiologically and are of a convenient size for performing extended experiments. We surgically implanted pacing leads, implantable cardiac monitors (ICMs), and pacing generators into the swine, along with external Fitbark 2.0 Collars to use activity levels as a measurement of quality of life. After the procedures the swine underwent rapid atrial pacing with the intention to induce persistent atrial fibrillation. Findings: An electrocardiogram (ECG) showed that the method of stimulating the right atrium of the heart induced persistent atrial fibrillation in pigs and decreased levels of activity, indicating a decline in their general health. This continued for &gt;7 days after atrial pacing was terminated. Overcoming challenges associated with animal dimensions and model design, we devised specific surgical techniques, including jugular cut-down, lateral cervical implantation coupled with antibiotic support, long sheaths, and customized styluses. These innovations were instrumental in achieving a successful AFib model and overcoming anatomical obstacles. Summary: Our study demonstrates the feasibility of creating a large animal model of AFib using Yucatan mini swine. This model closely resembles the clinical presentation of human AFib and could provide valuable insights into the disease mechanism and potential therapeutic strategies. Animal heart and vascular dimensions were the most challenging surgically.
Abstract 4123371: Hyperoxia is not a significant predictor of ICU mortality and is likely a surrogate parameter for reduced native cardiac function in patients supported with VA-ECMO
Authors: Ryan Ruaysungnoen, Connor Obrien, Alan Baik, sylvie Baudart, anja strehlow
Journal: Circulation (2024)

Intro: Hyperoxia has been associated with adverse outcomes in VA-ECMO patients. Whether hyperoxia represents a mechanism of mortality or is a surrogate for worse cardiac function is unknown. Aim: To determine patient characteristics, lab values, and hemodynamic parameters associated with increased mortality in VA-ECMO patients. Methods: Single-center retrospective cohort study at UCSF in VA-ECMO patients (2020-2023). Patients were categorized into 3 groups: Dead, Advanced Therapy-Free Survivors, and Advanced Therapy Survivors (survived to ICU discharge with LVAD or heart transplant). Wilcox rank sum and two sample proportion tests were performed. In-hospital mortality was evaluated using multiple logistic regression. Results: Of 179 patients, 87 died and 92 survived to ICU discharge. Of the survivors, 22 received advanced therapies. Compared to Advanced Therapy-Free Survivors, Dead patients had higher PaO2 levels (297[95% CI,164-400], p = 0.01). Dead and Advanced Therapy Survivors groups had similarly high PaO2 levels, but the latter group showed less acidosis and were more likely to have HFrEF (59%; 13/22; p = 0.02). ECMO support and VIS scores were similar. The multivariate model showed PaO2 is not associated with mortality (adjusted OR, 1.002 [95% CI, 0.99-1.004]; p = 0.131). Conclusion: Hyperoxia was associated with both death and advanced therapies, but did not predict mortality in a multivariate model. Advanced therapy survivors and patients that died were more likely to have HFrEF, suggesting that high PaO2 at cannulation reflects a proximal mixing cloud due to weak native cardiac function. Future work will analyze ECHO parameters to examine the association between hyperoxia and reduced cardiac output in VA-ECMO patients.
Abstract 4122717: An Epigenetic Drug, GSK126 Mitigates Endothelial to Mesenchymal Transition Attenuating Atherosclerosis in Diabetes
Authors: Misbah Aziz, Karin Jandeleitdahm, Abdul Waheed Khan
Journal: Circulation (2024)

Background: Endothelial to mesenchymal transition (EndMT) involves transformation of an endothelial to mesenchymal like cellular state. Recent studies implicate EndMT in atherosclerosis development. Diabetes is associated with both EndMT as well as accelerated atherosclerosis. Experimental evidence supports the use of epigenetic drugs that act on relevant epigenetic mechanisms to attenuate atherosclerosis. Recently, inhibition of a histone methyltransferase Enhancer of zest homolog 2 (EZH2) with GSK-126 attenuated atherosclerosis development. However, the role of EZH2 in induction of EndMT in diabetes induced atherosclerosis is not known. Methods: An in-vitro model of EndMT was generated using high glucose (HG) and TNF-α in human aortic endothelial cells (HAECs). EZH2 methyltransferase activity was inhibited using EZH2 specific inhibitor GSK-126. RNA sequencing was performed in this setting. EZH2 genetic knockdown (shRNA) in HAECs was also performed to validate role of EZH2 in EndMT. In addition, EZH2 mediated H3K27me3 and EndMT was assessed in atheroprone diabetic mouse model. Results: In HAECs, morphological changes as well as gene and protein expression confirmed TNF-α+HG induced EndMT, which was blunted by GSK-126. Elevated EZH2 mediated H3K27me3 activity by the TNF-α + HG stimulation was blunted with GSK-126 treatment. Furthermore, RNA sequencing identified several enriched pathways including AGE-RAGE signaling pathway in diabetic complications, focal adhesion, and leukocyte trans-endothelial migration directly relevant to EndMT and commonly deregulated in diabetic complications, which were rescued by EZH2 inhibition. Transcriptomic analysis showed that 242 genes including MMP2, NOS3 linked to EndMT were dysregulated. Interestingly, expression of 76 dysregulated genes in EndMT were rescued by GSK-126. EZH2 knockdown studies in HAECs also validated the role of EZH2 in EndMT. Furthermore, immunofluorescence staining identified elevated levels of H3K27me3 in the aortic endothelial layer of diabetic Apoe -/- mice. Co-localization of EndMT markers was observed in the endothelial layer of aortic sinus of diabetic Apoe -/- mice which was blunted with GSK-126 treatment. Conclusion: The study identified EZH2 inhibition as a novel therapeutic target in diabetes induced EndMT in atherosclerosis. These findings highlighted ongoing efforts to develop targeted therapies for diabetic patients who are at risk to develop cardiovascular disease.
Abstract 4114497: Shape Variations in Right Ventricular 3D Geometry are associated with adverse outcomes in Hypoplastic Left Heart Syndrome Patients: A Fontan Outcomes Registry using CMR Examination (FORCE) Study
Authors: Yue-Hin Loke, Ryan O'Hara, Jacqueline Contento, Nicole Marella, Lekha Anantuni, Susana Gaviria, Sarah Kollar, Ravi Vegulla, Rittal Mehta, Elias Balaras, YVES D'UDEKEM, Tarek Alsaied, Laura Olivieri, Uyen Truong, Francesco Capuano
Journal: Circulation (2024)

Introduction: Right ventricular (RV) function is critical to the long-term health of patients with hypoplastic left heart syndrome (HLHS). However, conventional measurements do not consider the range of RV morphology that may impact RV function and lead to adverse outcomes. In this study, we determined associations between RV shape and clinical outcomes of HLHS using statistical shape modeling (SSM) and a large cardiac magnetic resonance (CMR) multicenter registry. Methods: Three hundred and twenty-eight studies from unique HLHS patients in the F ontan O utcomes R egistry using C MR E xaminations (FORCE) were post-processed by a core lab at one institution, including volumetry and strain analysis. 3D end-diastolic models of RV were reconstructed using Mimics (Materialise). SSM was performed via Shapeworks Studio (NIH/NIGMS CIBC) to derive mean template and quantified shape variations (shape mode) representing deviation from the mean. RV shape relationship with mortality/heart transplant was assessed using bivariable/multivariable analyses with stepwise model selection. Results: The mean template from all 328 patients resembled a circumferentially dilated RV with loss of concavity in septal wall (Fig A). Several generalized variants were identified (Fig B), particularly p1 – a sigmoidal / “apical bulge” variant where the RV apex dilates and "wraps” around the hypoplastic left ventricle (Fig C). Twenty-eight patients (8.5%) experienced mortality/heart transplant at 2.5±2.4 years after CMR. On bivariable analysis, p1 was associated with mortality/heart transplant, along with larger indexed RV end-diastolic volume/mass and reduced global circumferential strain. On multivariable analysis, p1 and indexed RV mass were associated with mortality/heart transplant (Table). Conclusions: Statistical Shape Modeling can define the “usual” RV shape of HLHS. A sigmoidal shape variant is associated with adverse outcomes. SSM may provide patient-specific metrics to define RV dysfunction in HLHS.
Abstract 4117345: Predicting Downstream Aneurysmal Degeneration Following Type A Dissection Repair With Computational Fluid Dynamics
Authors: Christopher Jensen, Arash Ghorbannia, David Urick, Mary Moya-Mendez, Andrew Vekstein, Erik Draeger, Adam Williams, G Hughes, Amanda RANDLES
Journal: Circulation (2024)

Introduction: Acute type A aortic dissection (ATAAD) is typically treated by replacement of the ascending aorta (+/- root) and proximal arch. However, 70-85% of patients have residual distal dissection post-repair, and 20-40% require late reoperation for aneurysmal degeneration of the distal aorta (ADDA). Since an individual patient’s risk of ADDA cannot be accurately predicted, current guidelines recommend lifelong aortic surveillance imaging for all patients. Hypothesis: Computational fluid dynamics (CFD) simulations of aortic hemodynamics post-repair can accurately identify patients at late risk of ADDA. Methods: We performed CFD simulations of 50 patients following hemi-arch replacement for ATAAD. Patient-specific 3D models were generated from the aortic root to iliac bifurcation (including arch branches) from postoperative 0.6mm contrast-enhanced CT angiograms taken &lt;1 year after index repair (Figure). Exclusion criteria were known heritable thoracic aortic disease and absence of residual dissection. The primary outcome was ADDA, defined as late growth of the distal arch/descending thoracic aorta (DTA) to a diameter ≥5.5cm. Hemodynamic simulations were run for 6 cardiac cycles on a high-performance computing cluster using HARVEY, a CFD solver implementing the lattice Boltzmann method. The primary hemodynamic metric was time-averaged wall shear stress (TAWSS) ratio between the false and true lumens. Results: ADDA developed in 22 patients (44%) at a mean of 3.2 years postoperatively. There were no significant clinical differences between those with and without ADDA (Table). The development of late aneurysm growth was significantly associated with a higher TAWSS ratio in the proximal DTA ( p &lt;0.05, Figure). Conclusion: ADDA following hemi-arch repair for ATAAD is associated with significantly higher false lumen TAWSS as early as the first surveillance scan. CFD simulations may help clinicians risk-stratify patients years before they meet reoperation criteria.