tbuckley/cabot-search huggingface dataset:
Abstract 14464: Meta-Analysis Comparing Early vs Delayed Anticoagulation After Stroke in Patients With Atrial Fibrillation
Authors: Sahib Singh, Udaya Tantry, William W Ashley, Swecha Goel, Kevin Bliden, Paul Gurbel
Journal: Circulation (2023)

Introduction: Secondary prevention with anticoagulants is recommended for patients with acute ischemic stroke and atrial fibrillation (AF), but the timing of initiation of anticoagulation is debated. We performed a meta-analysis of the available studies. Methods: Studies comparing early (≤ 7 days) vs delayed (&gt; 7 days) start of anticoagulation after acute stroke in patients with AF were searched from online databases. The primary endpoints of interest were recurrent ischemic stroke, intracranial haemorrhage (ICH), and mortality at the longest available follow up. Random-effects model was used to estimate risk ratios (RR) with 95% confidence intervals (CI). Results: Four studies (2 randomized trials and 2 observational studies), with a total of 5,606 patients - 2,918 in the early group and 2,688 in the delayed group were included. The mean age was 79 years and 55% of patients were men. The follow up duration varied from 30 days to 6 months. No significant differences were found between the early and delayed anticoagulation groups with regards to risk of recurrent ischemic stroke (RR 0.80, 95% CI 0.51-1.27, p = 0.35) (Figure 1), ICH (RR 0.62, 95% CI 0.17-2.24, p = 0.47) or mortality (RR 0.88, 95% CI 0.64-1.22, p = 0.45) (Figure 2). Conclusions: In patients with acute ischemic stroke and AF, early initiation of anticoagulation has similar risk of recurrent stroke, ICH, and mortality, when compared with delayed initiation.
Abstract 13304: Intrinsic Morphology Influences the Natural History of Neo-Aortic Root Dilatation and Pathologic Neo-Aortic Regurgitation in Transposition of the Great Arteries
Authors: Aditya Sengupta, Kimberlee Gauvreau, Chrystalle K Carreon, Ji M Lee, Sanders Stephen P, Steven D Colan, Pedro J Del Nido, John E Mayer, Meena Nathan
Journal: Circulation (2023)

Introduction: Neo-aortic root dilatation and pathologic neo-aortic regurgitation (AR) can lead to significant late morbidity after the arterial switch operation (ASO) for dextro-transposition of the great arteries (dTGA). Hypothesis: The natural history of root dilatation in dTGA is influenced by intrinsic morphology. Aims: To i) delineate the natural history of root dilatation in repaired dTGA and ii) to histologically characterize the great arteries in unrepaired dTGA. Methods: A single-center review of patients who underwent the ASO from 07/1981-09/2022 was performed. Morphology was categorized as dTGA with intact ventricular septum (dTGA-IVS), dTGA with ventricular septal defect (dTGA-VSD), and double outlet right ventricle-TGA type (DORV-TGA). Echocardiographically-determined diameters and derived z-scores were measured at the annulus, sinus of Valsalva (SoV), and sinotubular junction (STJ) immediately before the ASO and throughout follow-up. Linear mixed-effects models assessed trends in dimensions over time. We also histologically examined the aortic and pulmonary roots of 10 cases of unrepaired dTGA from our Cardiac Registry. Results: Of 1359 patients meeting entry criteria, 593 (44%) had dTGA-IVS, 666 (49%) had dTGA-VSD, and 100 (7%) had DORV-TGA. At a median follow-up of 8.3 years (range 0.1-39.3 years), 129 (9.5%) patients had ≥moderate AR or required a neo-aortic valve or root reoperation ( Fig-A ). Overall growth of the root is shown in Fig-B . At baseline, there were no differences in annular, SoV, or STJ diameters between dTGA-IVS patients and dTGA-VSD or DORV-TGA patients. At 30 years, DORV-TGA patients had significantly larger diameters at the annulus (p&lt;0.001), SoV (p=0.039), and STJ (p=0.041) relative to dTGA-IVS patients ( Fig-C ). Specimens of the aortic and pulmonary roots from a representative case of unrepaired dTGA are shown in Fig-D . Conclusions: Longitudinal surveillance of the neo-aortic root is warranted long after the ASO.
Abstract 12853: [ <sup>64</sup> Cu]Cu-DOTATATE is Superior to [ <sup>68</sup> Ga]Ga-NODAGA-E[c(RGDyK)]2 (RGD) PET/CT Imaging In Detection and Quantification of Atherosclerosis: A Retrospective Analysis of a Phase 2 Trial Cohort
Authors: Harshvardhan A Khare
Journal: Circulation (2023)

Introduction: Inflammation and angiogenesis are central to development of atherosclerosis. [ 64 Cu]Cu-DOTATATE and [ 68 Ga]Ga-NODAGA-E[c(RGDyK)]2 (RGD) are PET tracers that can non-invasively visualize somatostatin receptor subtype 2 (SSTR 2 ) and α v β 3 integrin expression that represent inflammation and angiogenesis respectively. Hypothesis: Whether an imaging tracer of inflammation can be compared with a tracer of angiogenesis for detection and quantification of the atherosclerotic process in patients from a Phase II cancer trial cohort. Methods: A cohort of patients from Phase II trial were divided in three groups as controls (N=7), at risk (N=6) &amp; diseased (N=7). PET/CT scans with two different tracers were performed in all subjects. The scans were retrospectively analyzed, and tracer uptake (mean of maximum target-to-background ratios (mTBRmax)) were determined in 6 arterial segments. In addition, plaques from patients (N=7) undergoing carotid endarterectomy (CEA) were studied with autoradiography and immunohistochemistry. Results: [ 64 Cu]Cu-DOTATATE uptake in the disease group was significantly higher compared to the control group in the abdominal aorta (4.4 vs 2.1, p=0.02), thoracic aorta (3.0 vs 2.2, p=0.02), aortic arch (2.8 vs 2.2, p=0.03), left carotid artery (2.2 vs 1.3, p=0.02) and the average of all six aortic segments (2.7 vs 2.0, p=0.01) whereas all aortic segments in the disease group showed a higher but a non-significant difference compared to the control group with RGD uptake. A moderate correlation was found between the mean aortic uptake of [ 64 Cu]Cu-DOTATATE &amp; RGD (r=0.41, p=0.01) in patients from the disease group. SSTR 2 and α v β 3 expression was confirmed on ex vivo plaques along with tracer binding. Conclusions: An in vivo imaging marker of inflammation was superior to a marker of angiogenesis in discriminating levels of atherosclerosis. The two markers were weakly correlated in patients with known cardiovascular disease.
Abstract 17015: Mitophagy Facilitates Cytosolic Proteostasis to Preserve Cardiac Function
Authors: David R Rawnsley, Moydul Islam, Xiucui Ma, Chen Zhao, Adelita Mendoza, Minu Kumari, Jiajie Diao, Attila Kovacs, Jess Nigro, Abhinav Diwan
Journal: Circulation (2023)

Introduction: Protein quality control (PQC) is critical for maintaining sarcomere structure and function in cardiac myocytes. Mutations in PQC pathway proteins, such as CRYAB (arginine to glycine at position 120, R120G) and BAG3 (proline to lysine at position 209, P209L), induce protein aggregates with cardiomyopathy in humans. Novel observations in yeast and mammalian cells demonstrate mitochondrial uptake of cytosolic protein aggregates. The functional relevance of this pathway in myocardial proteostasis is unknown. Hypothesis: We hypothesize that mitophagy removes cytosolic protein aggregates in cardiac myocytes. Methods: Mice with inducible cardiac myocyte specific ablation of TRAF2 (TRAF2icKO), which impairs mitophagy, were assayed for protein aggregates with biochemical fractionation and super-resolution imaging in comparison to floxed controls. Transgenic mice expressing R120G CRYAB (R120G TG) were subjected to both TRAF2 gain-of-function (with AAV9-cardiac Troponin T promoter-driven TRAF2 transduction) and TRAF2 loss-of-function (with tamoxifen-inducible ablation of one Traf2 allele) in cardiac myocytes to determine the effect of mitophagy modulation on cardiac structure, function, and protein aggregate pathology. Results: Poly-ubiquitinated protein-rich aggregates accumulate in the cytosol and within mitochondria with desmin mislocalization in TRAF2icKO myocardium. CRYAB R120G and BAG3 P209L mutant proteins are taken up by isolated mitochondria. CRYAB R120G protein aggregates co-localize with damaged mitochondria and lysosomes by Coupa imaging, and accumulate in the mitochondrial fraction in R120G TG myocardium with upregulation of TRAF2 and induction of mitophagy. Adult-onset haplo-insufficiency of Traf2 accelerated mortality (P=0.003), impaired left ventricular (LV) fractional shortening (P&lt;0.001) and worsened mitochondrial morphology in R120G TG mice. AAV9-cTnT-TRAF2 transduction delayed mortality (P=0.027), rescued LV fractional shortening (P=0.039), reduced mitochondrial protein aggregates and improved desmin localization in R120G TG mice. Conclusions: Mitophagy facilitates removal of cytosolic protein aggregates and can be stimulated to ameliorate proteotoxic cardiomyopathy.
Abstract 17088: Pharmacological SERCA Activation Shifts Cardiac Fuel Preference Without Impairing Function in Obese Mice
Authors: Deveena R Banerjee, Mohsin Rahim, Clinton M Hasenour, Tomasz K Bednarski, Jamey D Young
Journal: Circulation (2023)

Introduction: Prior studies suggest that restoring Ca 2+ homeostasis by activating SERCA improves liver health and metabolism in a mouse model of metabolic syndrome. We were interested to know if these benefits extended to the heart. Here, we test the impact of pharmacological SERCA activation by CDN1163 on heart metabolism. We modeled data from in vivo 13 C tracer experiments to determine cardiac metabolic fluxes in obese mice at the end of an 8-week CDN1163 treatment period. Flux measurements were combined with echocardiography data to assess the effects of SERCA activation on heart function and metabolism. Methods: All mice in the study were hyperphagic Mc4r -/- mice. We studied three groups of Mc4r -/- mice at 16 weeks of age (n≥6 per group): mice fed a chow diet (Chow) or those switched to a western diet at 8 weeks of age (WD) ± CDN1163 (3 injections per week). Stable and radio-labeled isotopes were infused and blood was sampled from unrestrained, conscious mice through jugular vein and carotid artery catheters, respectively. Fluxes were estimated by fitting a mathematical model of liver and cardiac metabolism to 13 C enrichment measurements of plasma and tissue metabolites taken at the end of the infusion. A separate cohort of mice was used for echocardiography and gene expression analysis. Results: We found that WD increased absolute cardiac glycolytic, anaplerotic, and citric acid cycle (CAC) fluxes (~2-fold; p&lt;0.05). In contrast, CDN1163 treatment decreased these fluxes compared to both Chow and WD (~2-3-fold; p&lt;0.05). Additionally, the pyruvate partitioning between pyruvate carboxylase (PC) and pyruvate dehydrogenase (PDH) favored PDH with WD feeding (~2-fold), concurring with increased glycolysis. However, in WD+CDN1163 mice, pyruvate partitioning was restored to the Chow phenotype, favoring PC (p&lt;0.05 WD vs. WD+CDN11163), suggesting decreased reliance on glucose for the generation of acetyl CoA for the CAC. These metabolic shifts occurred without changes in cardiac function or compensatory structural remodeling of the left ventricle. Conclusions: CDN1163 treatment changes metabolic fluxes in the hearts of obese mice. These metabolic changes do not impact heart function.
Abstract 18199: Relationship Between Hospital Care Team Segregation Index and Cardiovascular Care for Black and White Patients
Authors: Adedoyin Johnson, Shannon Knapp, Janina Quintero Bisono, Dalancee Trabue, Ryan Yee, Francesca Williamson, Stephen Watty, Natalie Pool, Megan Thomas Hebdon, Wanda F Moore, Ekoh Yankah, Nneamaka Ezema, Nia Kimbrough, Johnnie Washington, Karen Lightbourne, Brownsyne Edmonds, Quinn Capers, David Brown, Denee Johnson, Jalynn Evans, Brandi Foree, Anastasia Holman, Courtland Blount, Brahmajee K Nallamothu, John Hollingsworth, Khadijah Breathett
Journal: Circulation (2023)

Background: High levels of hospital health care team segregation has been associated with worse outcomes for Black patients. We sought to determine whether hospital level segregation index (SI, degree of dissimilarity between composition of teams that care for Black versus White patients) was associated with care by a cardiologist, 30-day readmission, and 1-year survival for Black versus White patients with heart failure (HF). Methods: Using Optum’s de-identified Clinformatics® Data Mart Database, for commercial and Medicare plans, we examined SI among Black and White patients admitted with primary diagnosis of HF from 2010-2018. Hospitals were stratified into three SI groups based on tertiles from least to most segregated hospital teams. Generalized linear mixed-effects models were used to evaluate each outcome including effects of race, SI, race by SI as well as gender, age-adjusted Charlson Comborbidity Index, and hospital factors. For 30-day readmission and 1-year survival, we included effects of cardiology care, 2 and 3-way interactions of race, SI, and cardiology care. Results: Among 119, 272 patients, Black patients were less likely to be seen by a cardiologist compared to White patients across SI tertiles, particularly medium SI hospitals (OR 0.833, 95% CI 0.770-0.902). There was no significant difference in odds of readmission between races across hospital SI levels and whether seen by a cardiologist. For 1-year survival, the odds were significantly higher for Black patients compared to White patients across all SI levels ( Figure ). Conclusion: Black patients with commercial or Medicare insurance were less likely to be seen by a cardiologist for HF care than White patients across SI levels, particularly medium SI. Hospital SI levels did not demonstrate a consistent relationship between 30-day readmission and 1-year survival. Figure .
Abstract 17083: Aortic Luminal Contrast Attenuation Varies With Dissection Morphology and is Associated With Need For Intervention
Authors: Zachary M Feldman, Brandon J Sumpio, Sujin Lee, Marlena Sabatino, Charles C DeCarlo, Thomas Fedrigoni, Sunita Srivastava, Matthew Eagleton, Jahan Mohebali
Journal: Circulation (2023)

Introduction: Prognostication after acute Type B aortic dissection (aTBAD) may be limited when relying upon static computed tomographic angiography (CTA) images to evaluate a dynamic process. We performed an exploratory study to characterize variations in luminal contrast attenuation on CTA, as a surrogate for blood flow in dissection, and to determine whether the resulting parameters held prognostic value. Methods: Retrospective, single-institution data for patients with aTBAD were gathered from 1999-2020. Patients with prior dissection repairs were excluded. Dissection morphology was classified by the SVS/STS scheme and location/number of fenestrations. Hounsfield unit ratios (HUR) comparing lumina, phases, and aortic zone were calculated. Aortic growth, false lumen thrombosis, and need for intervention were evaluated with univariable logistic regression. Results: After exclusions, 85 patients were identified (mean age 61.9 years, 69.4% male). SVS/STS B 3,10 (20%) and B 3,5 (12.9%) predominated (Figure). Most fenestrations were in Zone 4/5 (56.5%) and associated with more equilibrated HUR (0.93) compared to dissections without fenestration (0.70, p = 0.04). Fenestration zone was not associated with HUR ( p = 0.59). Intervention occurred in 65.9%, most often for aneurysmal degeneration (43.8%), followed by visceral/limb ischemia (32.6%). Growth occurred in 28.2%. Increased arterial false-to-true HUR was strongly associated with eventual need for intervention (OR 25.3 [95% CI 4.15-188.4], p = 0.001) while increased delayed-to-arterial false lumen HUR was associated with decreased intervention (OR 0.49 [95% CI 0.25-0.89], p = 0.02). Conclusion: In patients with aTBAD, calculated permutations of HUR across lumina and between CTA phases may give insight into blood flow dynamics, which in turn likely impact need for intervention. Future prospective studies of time-resolved CTA are likely to hold significant prognostic value and alter management.
Abstract 15993: The Association of Aspirin With and Without Statin on Cardiovascular Outcomes in Primary Prevention Patients With Diabetes Mellitus
Authors: Pallavi Muluk, Jianhui Zhu, Floyd W Thoma, Martha Gulati, Eli Hay, Oscar C MARROQUIN, Amber Makani, Salim S Virani, Christie M Ballantyne, Suresh R Mulukutla, Anum Saeed
Journal: Circulation (2023)

Background: The role of aspirin in primary prevention of ASCVD amongst high-risk individuals with diabetes mellitus remains unclear. We investigated aspirin use with and without statin and its association with future ASCVD events in a cohort of real-world primary prevention patients with diabetes mellitus. Methods: Primary prevention patients with diabetes were stratified based on HbA1c levels (6.5-7%, 7-9%, &gt;9%) and 10-year ASCVD risk (High-risk [≥20%]). Aspirin use was defined as no use, seldom used (&lt;30% of the time), sometimes used (≥30% - &lt; 70% of the time), and often used (≥70% of the time). Cox regression assessed HRs of myocardial infarction (MI), stroke, and mortality with aspirin use. Results: Of 79, 597 patients with diabetes, 44.6% were classified as high-risk. These patients showed highest utilization of aspirin (45.7%) and statin (44.9%). Compared to high-risk patients with diabetes and an HbA1c of &gt;9% on both a statin and an aspirin, those on statin alone had higher risk of MI [HR MI 1.74 (1.44-2.212), p &lt;0.001], ischemic stroke [HR STROKE 2.52 (1.92-3.29), p &lt;0.001], and mortality [HR 1.67 (1.27-2.19), p &lt;0.001] (Table). Aspirin use alone was associated with higher risk of MI [HR 3.11 (2.42-4.00), p &lt;0.001], ischemic stroke [HR 3.12 (2.08-4.67), p &lt;0.001], and mortality [HR 3.77 (2.71-5.23), p &lt; 0.0004] in the high-risk population with HbA1c &gt;9% (Table). At all A1c levels, patients on no statin or aspirin were at significantly higher risk for MI, stroke, and mortality (Table). In high-risk patients with an HbA1c &gt;9%, ASA use ≥ 70% resulted in significantly lower risk of MI [HR 0.58 (0.49-0.69), p&lt;0.001)], ischemic stroke [HR 0.36 (0.28-0.46), p&lt;0.001] and mortality [HR 0.52 (0.42-0.66), p&lt;0.001]. Conclusion: Low dose aspirin may play a role in prevention of ASCVD events in high-risk patients with diabetes. Future studies can clarify the risk-benefit ratio of using aspirin with statin in patients with poor glycemic control for primary prevention of ASCVD events.
Abstract 16794: Trends and Predictors of In-Hospital Mortality in Elderly STEMI Patients With Cancer - 2016-2019
Authors: Revanth Reddy Bandaru, Kesavan Sankaramangalam
Journal: Circulation (2023)

Introduction: As cancer survivors have imported survival rates, they are more likely to develop cardiovascular diseases (CV), identifying elderly cancer patients who are at high risk of mortality with the development of ST-segment elevation myocardial infarction (STEMI) becomes important. Methods: Using 2016-19 National Inpatient Sample, we identified elderly (&gt;65 years) cancer patients with STEMI admissions and were analysed for demographic and clinic risk factors of all-cause mortality (ACM). Results: Of 13470 selected STEMI admissions with cancer patients, decreased cohort had higher rates of females (41.8 vs 33.8%, p&lt;0.001), blacks &amp; Asian/Pacific Islanders (8.1 vs 0.6%; 3.1 vs 2.5%; p=0.035), patients from lower income quartile (29.5 vs 25.2%, p&lt;0.001), with severe renal failure (2.4 vs 1.6%, p&lt;0.001) vs. those who survived. STEMI-cancer patients with hypertension, hyperlipidemia, smoker status, obesity, prior MI, and prior PCI/CABG had steady trends in ACM with DM interestingly showing improving trends in mortality (24% vs 18.1%) from 2016-19. Multivariate regression also did not reveal the worse impact of traditional cardiovascular risk factors on ACM. Conclusions: We identified elderly Hispanics being the only predictor of all-cause mortality in elderly cancer patients that develop STEMI.
Abstract 17147: Hypertriglyceridemia Associated With Peritoneal Dialysis
Authors: Mini G Varughese, Jose R Rivas Rios, Christie M Ballantyne
Journal: Circulation (2023)

Introduction: Chronic kidney disease and kidney replacement therapies (KRT) are associated with increased incidence of dyslipidemia and cardiovascular disease. In patients with chronic kidney disease, uremic dyslipidemia can cause qualitative and quantitative changes in the lipoproteins due to inflammation, malnutrition, and proteinuria. The major abnormalities include increase in triglyceride (TG) rich particles and reduced activity of lipoprotein lipase (LP). In this case, we present a patient who developed worsening hypertriglyceridemia after KRT changed to peritoneal dialysis (PD). Clinical Course: A 65-year-old female with end stage renal disease (ESRD) on PD, mixed dyslipidemia and hypertension who presented for elevated triglycerides 2084 mg/dL. Patient had been on KRT for 5 years and was switched to PD for the past 3 years. TG prior to starting PD was 203 mg/dL. Patient was started on atorvastatin 40 mg daily, Omega-3 Fatty Acids 2 g twice daily and substituted hypertonic glucose exchange with icodextrin for dialysate. TG improved to 391 mg/dL with these changes. Discussion: Hypertriglyceridemia is a common condition with management include lifestyle modifications and medications. In uremic dyslipidemia, there is increase in triglyceride-rich lipoproteins, small dense low-density lipoprotein particles, increased lipoprotein (a), and decreased high density lipoprotein. The pathogenesis of hypertriglyceridemia seen in PD is not well understood. There is overproduction of very low-density lipoprotein, peritoneal protein loss through drained dialysate, carbohydrate loading from the glucose based dialysate and reduced LP function contributing to the hypertriglyceridemia. This patient’s TG worsened when she was switched to PD from hemodialysis. TG improved with lifestyle modifications, medications and change in dialysate fluids. Hypertriglyceridemia associated with PD is rare, but it is important to recognize and treat to reduce risk of pancreatitis and cardiovascular complications.
Abstract 14807: Direct Carotid Sinus Nerve Stimulation in Anesthetized Human Subjects
Authors: Jonathan Baskin, Gilles Pinault, Elizabeth Heald, Dustin Tyler, Jeremy Dunning, Steve Majerus
Journal: Circulation (2023)

Introduction: Drug resistant hypertension is a growing clinical phenomenon across the world and there is a critical need for alternative therapeutic modalities. Hypothesis: A novel multi-contact electrode designed to interface with the carotid sinus nerve in conjunction with a unique implantation technique can selectively activate the baroreflex causing reversible drops in blood pressure (BP) &amp; heart rate (HR) in anesthetized humans. Methods: Patients undergoing therapeutic operations that necessitated carotid bulb exposure were prospectively enrolled in this IRB approved trial. Using a novel surgical approach, an application specific electrode was placed around the CSN followed by contact interface mapping to identify presumed baroafferent fibers which were selectively stimulated. Outcome measures included change in systolic BP (SBP), diastolic BP (DBP), and HR during and after stimulation. Results: 14 subjects met eligibility criteria. In 13, following correct contact identification, stimulation caused a 23±20mmHg (mean±SD) maximum drop in SBP with associated drops in DPB (11±9mmHg), and HR (10±9bpm). All subjects recovered immediately following stimulation withdrawal. All drops were significant (p&lt;0.001, t-test). In subjects with baseline SBP &gt;120mmHg (n=8), maximum SBP drop was 30±23mmHg, while subjects with baseline SBP &lt;120mmHg (n=5) exhibited a maximum SBP drop of 11±3mmHg. There was evidence of a positive dose (current) response relationship. Conclusions: Using a novel surgical approach and electrode, CSN stimulation in anesthetized human subjects caused a marked drop in BP/HR followed by rapid recovery with stimulation withdrawal. There was evidence of dose dependency.