tbuckley/cabot-search huggingface dataset:
Abstract 17732: Vitamin D Deficiency Causes Higher Mortality and Larger Haematoma Post Intracerebral Haemorrhage in Mice
Authors: Tsz Lung Lam
Journal: Circulation (2023)

Introduction: From clinical observation study, vitamin D deficiency (VDD) is found to be associated with worse outcome in intracerebral haemorrhage (ICH). However, whether association was causal remained unknown. This study aims to demonstrate the causal association between VDD and worse outcome post ICH, and to investigate its underlying pathophysiology mechanisms if any. Hypothesis: VDD caused higher mortality in ICH due to larger haematoma. The larger haematoma was due to dysfunctional platelets. Methods: An mice model for ICH was adopted. ICH was induced by injecting collagenase into the cerebrum. VDD was induced via special diet for 3 weeks pre-stroke, while normal group was fed with normal diet . Mortality was measured for seven days post-ICH. Haematoma volume was measured with haemoglobin assay, sectioning, and T2*-weighted MRI, and. Blood brain barrier leakage was evaluated with Evans blue extravasation study. Platelet count and platelet activation test was performed. Results: VDD caused higher mortality post-ICH. VDD also caused larger haematoma and more severe blood brain barrier leakage. Platelet count was found to be increased, and platelet activation test showed increased platelet activation. Conclusions: VDD caused higher mortality and morbidity in mice. The higher mortality and morbidity likely were attributable to the larger haematoma. The larger haematoma was likely attributable to dysfunctional platelets, causing more severe intracerebral bleeding and compromised haemostasis.
Abstract 176: The Pathological Role of Aldose Reductase in Isolated Cardiomyocytes Undergoing Hypoxia / Reoxygenation After Prior Exposure to High Glucose Concentrations
Authors: Miriam J Walter, Masakazu Shiota, Zhu Li, Matthew B Barajas, Takuro Oyama, Matthias L Riess
Journal: Circulation (2023)

Hyperglycemia increases the vulnerability of the cardiovascular system to ischemia/reperfusion (IR) injury. There are currently no effective therapeutic strategies. We hypothesized that hyperglycemia would increase glucose flux through the polyol pathway. Aldose reductase (AR) catalyzes the first step of this pathway by converting glucose to sorbitol. This reaction generates more oxidative stress due to the depletion of NADPH and osmotic stress caused by sorbitol accumulation, making the heart more susceptible to IR injury. This study aimed to better understand the injury mechanism in cardiomyocytes after high glucose exposure and IR injury. Confluent cardiomyocytes were exposed for 24 hours to 25, 50, or 100 mM glucose or 25 mM glucose with 25 or 75 mM sucrose concentrations added. The non-metabolizable sugar sucrose was used as an osmolarity control. Epalrestat, an AR inhibitor, was added at 0, 1, or 10 μM per well (n = 18 per group) during glucose or sucrose exposure. Cells were then subjected to 24 hours of hypoxic conditions (glucose-, sucrose- and serum-free media; 0.01% O 2 , 37 °C; hypoxic chamber) or normoxic conditions (complete media; 21% O 2 , 37 °C), followed by a 2-hour reoxygenation period in normoxic conditions. Cell injury was quantified by measurement of lactate dehydrogenase (LDH) release. Data were normalized to 25 mM glucose after control/normoxic conditions without AR inhibitor. A three-way ANOVA was conducted to compare groups, followed by the Holm-Šidák test. Increasing glucose concentrations lead to increased cell damage after hypoxia/reoxygenation. Adding the AR inhibitor during the glucose exposure period reduced LDH release after hypoxia/reoxygenation in a dose-dependent manner. The addition of sucrose did not increase cell injury. The AR inhibitor did not affect cells exposed to sucrose. The polyol pathway may play a dominant role in increased cell injury by hyperglycemia after hypoxia/reoxygenation.
Abstract 13494: Histopathological Analysis Indicates a Significant Role of Myocardial Perfusion Disturbance in Tissue Lesion in Chronic Chagas’ Cardiomyopathy Experimental Model
Authors: Camila G Fabricio, Denise M Tanaka, Jose A Marin-Neto, Luciano Oliveira, Fernando F Ribeiro, Alexandre T Todorovic Fabro, Sabrina S Batah, Jorge M Cabeza, Minna M Romano, Marcus V Simoes
Journal: Circulation (2023)

Introduction: Coronary microvascular perfusion disturbance (MPD) is frequently found in Chronic Chagas' cardiomyopathy (CCC), but its role in tissue lesion and left ventricular dysfunction progression is still unclear. Hypothesis: As MPD is associated with more severe subendocardial myocardial injury, we tested the hypothesis that histopathological changes in subendocardial layer could be quantitatively correlated to MPD in experimental model of CCC in hamsters. Methods: Female Syrian hamsters (n=23) infected with 3.5x10 4 blood trypomastigote forms of T. cruzi ( Y strain ) and their respective controls (n=6) were studied. At 8 months after infection, the animals underwent in vivo high-resolution myocardial rest perfusion scintigraphy with 99m Tc-Sestamibi and transthoracic echocardiography. After euthanasia, the myocardial tissue was processed for quantitative histopathological analysis of mononuclear infiltrate index (MII) using hematoxylin-eosin staining and myocardial fibrosis using picrosirius staining in LV wall layers: subendocardium, mesocardium and subepicardium. Results: Fourteen animals (61%) presented rest MPD. The area of MPD was negatively correlated with LVEF (R=-0.5; p=0.02), and positively correlated with LV diastolic diameter (R=0.83; p&lt;0.01). Animals with MPD exhibited increased extent of myocardial fibrosis in the subendocardial layer (0.67 + 0.18%) as compared to control animals (0.47 + 0.15%), p=0.03. However, the extent of total transmural fibrosis or fibrosis in other myocardial layers were similar among groups. The group with MPD presented higher values of MII in every myocardial layer as compared to controls and animals without MPD. However, only the MII in the subendocardial layer presented positive correlation with the extent of rest MPD (R=0.55, p=0.001). Conclusions: Our results indicate that MPD is significantly correlated with histopathological changes located in the subendocardial layer of LV walls. These results suggest that MPD may act as an amplifying and localizing factor for inflammation and fibrosis, suggesting a relevant role for myocardial hypoperfusion in the mechanisms of myocardial injury in CCC.
Abstract 17607: Clonal Hematopoiesis of Indeterminate Potential (CHIP) is an Independent Risk Factor for Cardiomyopathy in Patients With Solid Malignancy
Authors: Carlos F Matute Martinez, Ritujith Jayakrishnan, Ana Ferrigno Guajardo, Etienne Leveille, Derrick Lin, Yunju Im, Anthos Christofides, Nathan Chen, Lauren A Baldassarre, Jennifer VanOudenhove, Stephanie Halene, John Hwa, Jennifer M Kwan
Journal: Circulation (2023)

Background: Somatic mutations linked to clonal hematopoiesis of indeterminate potential (CHIP) are associated with increased risk of cardiomyopathy (CM) and all-cause mortality in the general population. However, this relationship is less clear in patients with solid malignancy, and it is unclear if knowing CHIP status can identify patients at risk for adverse cardiac outcomes. Objectives: To determine the association between CHIP and the development of CM in patients with solid malignancy, as well as overall survival (OS). Methods: CHIP mutation status was determined by next-generation sequencing of DNA from peripheral blood samples of 173 participants with solid malignancy. A somatic variant pipeline using MUTECT2 selected for somatic CHIP variants with a variant of allele frequency between 2-40%. CHIP association with the outcomes of OS and CM was assessed using Kaplan-Meier survival and Cox regression analyses. Results: Participants’ median age was 63 years, and 76% were female. CHIP mutations were detected in 39% of participants, most commonly in DNMT3A, TET2, and IDH2 genes. Majority were breast cancer patients 54% (n= 94). More patients with CHIP had diastolic dysfunction (21% vs 9%, p=0.037) compared to those without CHIP. After a median follow-up of 36 months, those with CHIP had an earlier time to death and earlier time to CM. Cox regression analysis showed that metastatic disease (HR 2.92, P=0.003) and male gender (HR 2.35, P=0.03) were independent risk factors for death, and CHIP (HR 2.120, P=0.02) was an independent risk factor for CM (Figure). Conclusions: Our study showed that solid malignancy patients with CHIP had worse outcomes with shorter time to death and shorter time to CM, with CHIP being an independent risk factor for CM. CHIP assessment can help us identify patients who may be at greater risk for adverse cardiovascular events during and after cancer therapy and who may warrant closer monitoring.
Abstract 17600: The 10,000 Women Project: A Deeper Dive Into the Social Determinants of Cardiovascular Health of Black Women
Authors: Rand Ibrahim, Telisa Spikes, Stacy Jaskwhich, Gina P Lundberg
Journal: Circulation (2023)

Introduction: Factors influencing the severity of cardiovascular diseases (CVD) in women are not fully understood. Social determinants of health (level of education, income, insurance) play an important role in predicting CVD especially in the Black women community. Hypothesis: We hypothesize that having better social determinants of health will predict better behavioral changes after a 6-month follow up from a community screening effort. Methods: Between 2015 and 2018, CVD screening and education across the southeastern metropolitan region was provided as “The 10,000 Women Project”. Social determinants of health (insurance, level of education, income), comorbidities, CVD risk factors, activity, and dietary assessment were collected. Behavioral changes were assessed at a 6-month follow-up. Logistic regression analysis was used to assess for associations while adjusting for covariates. Results: A total of n=945 Black women were screened, 16% childbearing age (20-40yr). The majority had health insurance (93%) and at least college-level education (88%). The majority (49%) had a household income &gt;$48,000. At least one CVD (HTN, DM, stroke, heart attack) was reported in 45% and smoking was reported in 11%. Only 28% met the AHA exercise recommendation (≥ 30minutes 3x/week) and 42% limited their salt intake. At 6-month follow-up, there was 60% odds of increased exercise (OR=1.6, p=0.034) among those with college-level education or higher. Also, they experienced 70% improvement in diet (1.7, p=0.024), a 60% weight loss (1.6, p=0.047), and 90% increase in regular BP measurement (1.9, p=0.016). Higher household incomes were associated with 50% higher odds of improving exercise (OR=1.5, p=0.008) and dietary habits (OR=1.5, p=0.01). Adjustments were made for age, demographics, CVD risk factors and comorbidities. Conclusions: We report greater positive changes in Black women with better baseline social determinants of health after a 6-month follow-up. Systemic changes are needed to address these underlying players of CVD diseases.
Abstract 17432: Utilization of Heart Failure Therapies: Assessing Trends and Adoption of Updated Guideline Directed Medical Therapy Following the 2022 Heart Failure Guideline Release
Authors: Aparna Narendrula, Rochell Issa, Wai Hong W Tang, David Kaelber, Deborah H Kwon
Journal: Circulation (2023)

Introduction: The adoption rate of new guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) is unclear. Thus, we assessed temporal trends in GDMT prescription following the release of the 2022 ACC/AHA heart failure guidelines. Methods: Using the TriNetX database, we identified HFrEF patients with an EF = 40%. Seven 2-month time windows between April 1, 2022 and May 31, 2023 were analyzed. Treatment categories included sacubitril (proxy variable for angiotensin receptor/neprilysin inhibitor), angiotensin-converting enzyme inhibitors (ACEi), beta blockers, mineralocorticoid-receptor antagonists, sodium glucose transport 2 inhibitors (SGLT2i), isosorbide dinitrate, ivabradine, hydralazine, and ICD/CRT. Incidence rate and prevalence of GDMT prescription were assessed over 14 months post-guideline publication. Results: Analysis included 167,740 HFrEF patients. Sacubitril prevalence doubled between 2022 (18.326%) and 2023 (36.779%), with a higher rate of increase after January 2023. ARB prescription prevalence increased from 39.031% to 58.696%, with notable incidence growth after January 2023. Prevalence of SGLT2i prescription increased from 14.794% in 2022 to 34.14% in 2023. Incidence rates for other therapies also showed upward trends, resulting in increased overall therapy prevalence. Slightly lower 1-month hospitalization (46.378% vs 46.654%) and mortality (7.327% vs 7.549%) were observed in the 14 months after guideline publication compared to the 14 months prior. Conclusions: Improved adherence to GDMT guidelines has occurred since the release of the 2022 guidelines. Notably, utilization of ARNIs and SGLT2 inhibitors significantly increased. However, prescription rates for these novel therapies were below 50%, highlighting the need to expand access to a larger proportion of HFrEF patients.
Abstract 15982: Management and Follow-Up of Inpatients With Cardiac Implantable Electronic Devices and Bacteremia With and Without Electrophysiology Consultation
Authors: Edward R Horton, Richard Saporito, David Fleece, John T Enevoldsen, Edmond Cronin, Joshua M Cooper, Isaac R Whitman, Chethan Gangireddy
Journal: Circulation (2023)

Introduction: Transvenous cardiac implantable electronic device (CIED) infection is a significant cause of morbidity and mortality. Expert consensus recommends a multidisciplinary approach to bacteremia in the context of CIED incorporating both infectious disease (ID) and electrophysiology (EP) consultation to balance the risks of infection with those of CIED removal. Hypothesis: Not all patients with CIEDs and bacteremia are evaluated with EP consultation, and this difference is associated with variability in management. Methods: Using the EMR, we retrospectively identified inpatients with a CIED and a positive blood culture across three hospitals: one academic, one specialty and one community. True infection versus contaminant was determined by an EP or ID attending at the time of presentation or adjudicated retrospectively by an EP who performs extractions. We examined the rates of EP consultation based on hospital site, CIED removal and appropriate follow-up in those without CIED removal. Fisher’s exact test was used to compare the rates of follow up. Results: We identified 88 inpatients with a CIED and positive blood culture between January 2020 - February 2023. True bacteremia was adjudicated in 48 patients (55%). Of these patients, 24 were seen by EP (50%), 22 were seen by EP and ID (46%), and 14 were seen by neither (29%). Patients admitted to an academic hospital were more likely to be seen by EP (22/38, 57%) than those admitted to a specialty or community hospital (2/10, 20%). CIED removal was performed in 15 of 24 patients seen by EP (63%). Patients seen by EP were significantly more likely to have documented plans, repeat blood cultures after antibiotic completion, and appropriate follow up than those not seen by EP (24/24 100% vs. 3/24, 8%, p&lt;0.001). Conclusion: Even at a high-volume extraction center, EP consultation for patients with true bacteremia in the context of CIED only occurred 50% of the time. Patients admitted to an academic hospital were more likely to be seen by EP than at a community or subspecialty hospital. EP consultation is important for all bacteremic patients with CIEDs, not only to recommend extraction if appropriate, but also to ensure timely follow-up and management of treatment failure, consistent with expert consensus.
Abstract 17590: Association of Intensive vs Standard Blood Pressure Lowering With 1-year and 2-year Changes in Cardiac Biomarker Levels: Findings From SPRINT
Authors: Spencer L Shastid, Djhenne Dalmacy, Simon Ascher, Christie M Ballantyne, VIJAY NAMBI, James A de Lemos, Jarett D Berry
Journal: Circulation (2023)

Background: The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that intensive systolic blood pressure (SBP) lowering was associated with marked reductions in cardiovascular disease (CVD) endpoints. We recently reported that intensive SBP lowering was also associated with a small increase in high-sensitivity cardiac troponin T (hs-cTnT) and a large decrease in N-terminal pro-B-type natiuretic peptide (NT-proBNP) over 1-year. However, data on longer term biomarker changes with intensive versus standard SBP lowering have not been previously reported. Methods: hs-cTnT and NT-proBNP were measured at baseline, 1 year, and 2 years from stored specimens in SPRINT participants. Changes in biomarkers were evaluated continuously on the log scale with interval censoring of participants with CVD events. The effect of intensive SBP lowering on biomarker changes was assessed using linear regression models with treatment effects reported as geometric mean ratios. Results: Of 9,361 SPRINT participants, hs-cTnT and NT-proBNP were measured in 8,828 (baseline), 7,887 (Year 1), and 7,463 (Year 2) free of CVD events. Intensive SBP lowering led to a 3% increase in log-transformed hs-cTnT from baseline to Year 1, but there was no significant change observed from baseline to Year 2. In contrast, intensive SBP lowering led to a consistent 10% decrease in NT-proBNP from baseline to Year 1 and to Year 2. NT-proBNP levels increased slightly from Year 1 to Year 2 in both treatment arms such that the 1-Year treatment effect for intensive SBP lowering was maintained to Year 2 (see Table). Conclusions: Intensive SBP lowering was associated with a transient, modest increase in hscTnT at Year 1 that was no longer present at Year 2. In contrast, intensive SBP lowering was associated with a persistent reduction in NT-proBNP at both 1 and 2 years follow-up. These findings highlight the complex responses of cardiac biomarkers to intensive SBP lowering.
Abstract 17610: A Novel Approach Using Deep Neural Networks on Clinical Cardiac MRIs Can Identify Patients With Clonal Hematopoiesis of Indeterminate Potential With High Accuracy
Authors: Allen Ryu, Anthos Christofides, Carlos Matute Martinez, Ritujith Jayakrishnan, Shawn Ahn, Ana Ferrigno Guajardo, Jeacy Espinoza, Nathan Chen, Alokkumar Jha, Yunju Im, Stephanie Halene, Jennifer VanOudenhove, HAMID MOJIBIAN, James Duncan, Nicha Dvornek, Jennifer M Kwan
Journal: Circulation (2023)

Background: Clonal hematopoiesis of indeterminate potential (CHIP) has been shown to be an independent risk factor for heart disease and heart failure. DNA sequencing is the gold standard to diagnose CHIP. It is unclear if deep learning techniques using routine clinical imaging can aid in identifying those who are likely to have CHIP and thus likely at increased risk for heart disease and heart failure. Hypothesis: We hypothesized that deep learning models trained on routine cardiac MRI (CMR) would be able to help predict who has CHIP Methods: We enrolled patients into an IRB approved study to evaluate for CHIP and associated imaging findings. Whole exome sequencing and our somatic variant pipeline was used to identify those who had CHIP. Various machine learning techniques were employed for training and testing, including SVM, random forest and convolutional neural networks (CNN) to predict who had CHIP from CMR imaging. Results: We enrolled 98 unique patients with CMR and found that 40 (41%) had CHIP. Majority were female 65 (66%) and there was no significant difference in median age between CHIP vs no CHIP (69, IQR 62-78 vs 65, IQR 54-72). There were no significant differences between CHIP vs no CHIP patients in co-morbidities such as CAD, DM, HTN, HF. Compared to SVM and random forest, the best performing model with high sensitivity, specificity and accuracy was derived from CNN (AUC 0.64 vs 0.71 vs 0.85 respectively). We found that multi-view MRI inputs were more accurate than single view MRI inputs for the CNN model. Using an unsupervised approach with CNN and multi-view input, we were able to predict CHIP with 82% accuracy. Conclusions: CNN is a promising deep learning technique that can accurately classify CHIP and thus those at higher cardiovascular disease risk. Ongoing analyses are underway to validate these findings using the UK Biobank and TOPMED datasets and predict who will develop cardiomyopathy with CHIP.
Abstract 17596: Association of Racial-Ethnic Disparities and Frailty on Adverse Outcomes in Geriatric Patients Undergoing Elective Percutaneous Left Atrial Appendage Closure With Watchman Device
Authors: Shivaraj Patil, Avica Atri, Chaitanya Rojulpote, Sahana Tito, Abhijit Bhattaru, Viha Atri, Ola Khraisha
Journal: Circulation (2023)

Introduction: Use of left atrial appendage closure (LAAC) has become more widespread in the geriatric population. Frailty, a geriatric syndrome, is associated with significant morbidity and mortality. Hypothesis: Race/Ethnicity influences frailty status and may differentially impact adverse outcomes in elective LAAC procedure. Methods: Patients aged ≥65 years who underwent elective LAAC were identified using ICD-10 procedure code 02L73DK from 2016-2018 HCUP-NIS Database. Hospital Frailty Risk Score (HFRS) was calculated for each patient based on 109 ICD-10 diagnosis codes and classified into non-frail (HFRS &lt; 5) and frail (HFRS score ≥ 5) groups. Charlson comorbidity index (CCI) was used to assess comorbidity burden. In-hospital major adverse event (MAE) was defined as the composite of mortality, stroke (ischemic or hemorrhagic) or TIA, bleeding or transfusion, vascular complications, myocardial infarction, systemic embolization, and pericardial effusion or tamponade requiring pericardiocentesis or surgery. Outcome was in-hospital MAE. Multivariate regression analysis was used to assess the association of race/ethnicity and frailty on MAE. Results: 27,155 patients (Age = 77.3 ± 6.4 years; Female = 42.4%, White: 88%, Black: 3.4%, Hispanic:5.2%, Other: 3.4%) were included. Overall, the prevalence of frailty was 12.5% (White:12.4%, Black: 13.7%, Hispanic: 11.8%, Other: 13%). Overall, in-hospital MAE was 4.7%, with increased rates in frail patients (4% vs.9.6%; p&lt;0.001). Rates of in-hospital MAE were frail-White: 9.3%, frail-Black: 8%, frail-Hispanic:20.6%, and frail-Other: 4.2% (p&lt;0.001). On multivariate analysis, frail-White and frail-Hispanic patients were at increased risk of in-hospital MAE compared to non-frail patients (Figure). Conclusion: Further research is needed to highlight disparities by race/ethnicity and to identify potentially modifiable factors to mitigate adverse events in frail geriatric population undergoing LAAC.