tbuckley/cabot-search huggingface dataset:
Abstract 15233: Stem Cell Therapy for the Treatment of Chronic Ischemic Heart Disease: A Review
Authors: Roberto G G Carbone, Simone Negrini, Giuseppe Murdaca, Francesco Puppo
Journal: Circulation (2023)

Introduction: Chronic ischemic heart disease remains a major cause of morbidity and mortality. Several clinical trials have been performed to evaluate benefit of stem cells transplantation to restore cardiac function. Aim: The review reports potential benefit of stem cells therapy in chronic ischemic heart disease. Methods: Trials were selected applying as search terms “bone marrow cells”, “stem cells”, “mesenchymal cells”, and “chronic ischemic heart disease” in www.pubmed.gov and Cochrane library from 2005 to 2023. Studies were included if they were randomized blinded trials, randomized unblinded trials, non-randomized trials. Left ventricular ejection fraction (LVEF) increase and New York Heart Association (NYHA) class decrease were the outcome parameters at 6 and 12 months follow up. Results: We analyzed 20 trials including 1812 patients (939 treated, 789 males, mean age 62 years). Bone marrow (BMC), peripheral blood (PBC), cardiac (CDC) or mesenchymal (MES) stem cells were utilized in 8, 5, 7 trials, respectively. Total number of transplanted cells ranged from 5 x 10 6 to 1,300 x 10 6 (median 70 x 10 6 ) depending on cell type, cell population purification, and transplantation route. Transplant procedure was intracoronary in 9 trials and intramyocardial in 11 trials. At baseline mean LVEF was 33.5 % (range 27.1 - 46.0 %). Eleven trials reported a statistically significant percent LVEF increase between 4% to 19% (mean 9.6%) at 12 months after stem cells transplantation ( p values ranging from 0.05 to 0.001). BMC and PBC stem cells were utilized in all these studies. A significant correlation was found between number of transplanted cells and percent LVEF increase (Pearson correlation coefficient 0.74, p = 0.01). Conclusions: Results seem to favor a moderate positive effect of stem cells transplantation in chronic ischemic heart disease at 12 months follow up. The positive effect was correlated with the number of transplanted cells. However, caution should be exercised in the evaluation of clinical trials due to the different stem cells utilized, transplant protocols and endpoints.
Abstract 15515: SGLT2 Inhibitor Empagliflozin Increases Fatty Acid Oxidation, Coupling Between Glycolysis and Glucose Oxidation, and Decreases Left Ventricular Hypertrophy in Mice With Hypertrophic Cardiomyopathy Due to Myosin R403Q Mutation
Authors: Tomas Baka, Jarrod Moore, Fuzhong Qin, Huamei He, Jordan M Chambers, Dominique Croteau, Raghuveera Goel, Aifeng Zhang, Hunter Smith, James A Balschi, David R Pimentel, Christine E Seidman, Jonathan G Seidman, Andrew Emili, Wilson S Colucci, Ivan Luptak
Journal: Circulation (2023)

Background: A metabolic switch from fatty acid oxidation (FAO) to glycolysis associates with LV hypertrophy (LVH). Glucagon signaling increases FAO in the heart and sodium-glucose co-transporter 2 inhibitors (SGLT2i) raise glucagon/insulin ratio (GIR) in patients. We have shown that SGLT2i reprogram cardiac metabolic genes favoring FAO, yet the mechanism is unknown. Hypothesis: SGLT2i increases GIR, thereby increasing FAO and glycolysis/glucose oxidation coupling (GGC), which in turn attenuates LVH and fibrosis in a murine model of HCM (R403Q myosin mutation). Methods: Mice 9 weeks of age were treated ± SGLT2i empagliflozin (EMPA, 0.15 mg/g chow). After 2 weeks, prior to LVH onset, myocardial transcriptomic analysis was performed. After 16 weeks, echocardiography, proteomics, fasted GIR, and histology were obtained. Glucose fluxes, energetics and 13 C substrate oxidation were measured in isolated beating hearts by 31 P and 13 C NMR spectroscopy. Results: R403Q mice had ↓GIR which was normalized by EMPA. Transcriptomics (2 weeks) and proteomics (16 weeks) confirmed downregulation of electron transport and FAO pathways, and upregulation of LVH and fibrosis pathways. At 16 weeks, R403Q hearts exhibited LVH, fibrosis, ↓diastolic function and ↓contractile reserve (rate pressure product increase between low and high workload). Metabolically, R403Q had ↑glucose uptake and ↓GGC with ↑lactate production; ↓FAO and impaired energetics (↓free energy of ATP hydrolysis, ΔG ~ATP , at both workloads). The HCM phenotype and all measures of metabolic dysfunction were partially or completely prevented by EMPA. Conclusion: R403Q hearts display marked metabolic reprogramming that appears early in the disease process and leads to energetic dysfunction. SGLT2i corrects GIR, attenuates metabolic reprogramming and the energetic, structural and functional features of HCM. SGLT2i and possibly other measures to modulate glucagon signaling hold therapeutic potential in HCM.
Abstract 17437: Estimated Lifetime Benefits of Combination Therapy With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Non-Steroidal MRAs in Patients With Type 2 Diabetes and Albuminuria
Authors: Brendon L Neuen, Vlado Perkovic, George L Bakris, Hiddo Lambers Heerspink, Muthiah Vaduganathan
Journal: Circulation (2023)

Introduction: Sodium glucose co-transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and the non-steroidal mineralocorticoid receptor antagonist finerenone all reduce cardiovascular events and mortality in patients with type 2 diabetes. However, the lifetime benefits of combination therapy with all three medications are not known. Aim: To estimate lifetime gains in cardiovascular event-free and overall survival with combination SGLT2i, GLP-1RA, and finerenone in patients with type 2 diabetes and albuminuria. Methods: We used individual participant data from the CANVAS and CREDENCE trials and trial-level data from 8 GLP-1RA trials and 2 finerenone trials (FIDELIO and FIGARO) to estimate the relative effects of combination therapy on cardiovascular and mortality outcomes. Using nonparametric age-based methods, we applied combined treatment effects to placebo treated patients with urinary albumin:creatinine ratio ≥30 mg/g in the pooled CANVAS and CREDENCE trials. Results: The aggregate hazard ratio comparing combination therapy versus conventional standard of care for major adverse cardiovascular events (MACE; nonfatal myocardial infarction, nonfatal stroke or cardiovascular death) was 0.65 (95% CI 0.55-0.76) (Figure). For a 50-year-old, estimated event-free survival from MACE was 18.0 years with placebo and 21.2 years with combination therapy (3.2 years gained, 95% CI 2.1-4.2; Figure). Estimated gains in survival free from hospitalised heart failure, cardiovascular death, and all-cause death with combination therapy in a 50-year-old person were 3.3 (95% CI 2.5-4.1), 2.2 (95% CI 1.2-3.1), and 2.5 years (95% CI 1.4-3.5) respectively, with benefits evident across all ages studied. Conclusions: Combination treatment with SGLT2i, GLP-1RA and finerenone in patients with type 2 diabetes and albuminuria is projected to afford clinically important gains in cardiovascular event-free and overall survival.
Abstract 14142: Patterns of Renin Angiotensin Aldosterone Inhibitor Use in Patients After Hospitalization With Acute Kidney Injury
Authors: Dhruv M Krishnan, Jiming Fang, Dennis T Ko, Douglas Lee, David Naimark, Karen Tu, Moira K Kapral, Jacob A Udell, Cynthia Jackevicius
Journal: Circulation (2023)

Background: Renin-angiotensin system inhibitors (RASi, i.e., ACEIs and ARBs) are vital to chronic disease management and they are often held in the setting of AKI. Reinitiation after hospital discharge requires careful coordination and puts patients at risk of inappropriately remaining off RASi. Aims: Characterize patterns of RASi use post-AKI hospitalization and identify factors associated with RASi discontinuation and reinitiation after discharge. Methods: A retrospective cohort study using ICES administrative data was conducted among adults ≥66 on RASi and discharged after hospitalization with AKI in Ontario (2015-2019). Prescription claims were used to identify patients who experienced RASi discontinuation (no RASi script renewal) after discharge. These patients were then followed for an additional 6 months to monitor for reinitiation. Modified Poisson and Cox regression models were used to identify factors associated with discontinuation and reinitiation, respectively, censoring those who died or were readmitted prior to reinitiation. Results: The cohort included 84,598 patients, mean age 80.3 years, 50.8% male. Overall, 42.2% continued their RASi, 37.1% discontinued, and use was indeterminable for the 20.7% who were readmitted or died before their prescription elapsed. Of the 31,390 patients with RASi discontinuation, 47.4% did not reinitiate and 34.8% reinitiated. Discontinuation was more likely in patients with CKD (RR = 1.13, 95% CI 1.10-1.16) or on diuretics (RR = 1.06, 95% CI 1.03-1.09). Reinitiation was more likely in patients in the highest income quintile (HR 1.08, 95% CI 1.02-1.15) or on diuretics (HR = 1.09, 95% CI 1.04-1.13), and less likely in patients with HF (HR = 0.89 95% CI 0.85-0.93), dementia (HR = 0.72, 95% CI 0.67-0.76), or rural residence (HR = 0.88, 95% CI 0.82-0.94). Conclusions: After hospitalization with AKI, nearly 2 in 5 patients discontinued their RASi at discharge, with one-third of these patients restarting within 6 months. Several patient-, provider-, and system-level factors were associated with patterns of RASi use after discharge. These can be used to identify patients at higher risk of experiencing RASi interruption, which may highlight opportunities for optimization of RASi use to improve patient care.
Abstract 16300: Genetic Influences on Cardiovascular Deaths During Various Follow-Up Lengths in the 45-Year Longitudinal Twin Study
Authors: Jun Dai
Journal: Circulation (2023)

Background: Genetic factors are known to affect cardiovascular and coronary heart death. The more deaths occur during the longer follow-up period in a longitudinal study. However, it is unclear whether follow-up lengths affect genetic influences on the mortality from total cardiovascular (CVD) and coronary heart diseases (CHD). Objective: To determine genetic influences on the mortality from CVD and CHD over various years of follow-up in the 45-year longitudinal National Heart, Lung, and Blood Institute (NHLBI) Twin Study. Method: A total of 1024 middle-aged, white male, veteran twins (512 pairs), including 253 monozygotic and 261 dizygotic twin pairs, were initially enrolled during 1969-1973 and then followed up on vital status and causes of death through December 31, 2015. Tetrachoric correlation coefficients were estimated for CHD and CVD death at 20, 30, and 45 years of follow-up, respectively. Genetic and environmental influences on the death were quantified using the best-fitting structural equation model selected with the smallest Akaike's Information Criterion value and the parsimony rule. Results: The age at death ranged from 43.9 to 97.3 years over a 45-year follow-up. Tetrachoric correlation coefficients in dizygotic twins were less than half of that in monozygotic twins over 20, 30, and 45 years of follow-up for CVD but over 20 and 30 years for CHD, respectively. Dominant genetic factors explained 40% (95% CI 5% ~ 68%), 39 % (16% ~ 59%), and 24% (4% ~ 43%) of variation in CVD death over 20, 30, and 45 years of follow-up, respectively, while the remaining variation in CVD death was explained by unique environmental factors during each follow-up period. For CHD death, unique environmental factors explained all variation over 20 and 45 years of follow-up. By contrast, dominant genetic factors explained 26% (95% CI -6% ~ 53%) variation in CHD death over 30 years of follow-up while the remaining variation was explained by unique environmental factors. Conclusion: Dominant genetic factors consistently influence cardiovascular mortality over 20 to 45 years of follow-up, implying a twin study of cardiovascular death can control for genetic confounding during this period.
Abstract 16291: Regional Variability in Cardiovascular MRI Access and Utilization in the U.S. Population From 2017 to 2019
Authors: Jennifer M Li, David R Ho, Nazia Husain, J. P Finn, James W Goldfarb, Anthon R Fuisz, Ibrahim M Saeed, Kim-Lien Nguyen
Journal: Circulation (2023)

Background: Despite clinical guidelines and scientific data supporting the use of cardiovascular magnetic resonance (CMR) imaging in multiple applications, CMR continues to be underutilized in the United States (U.S.). Objective: This study aims to capture geographic variability, access, and CMR practice patterns in the U.S. between 2017 and 2019. Methods: Commissioned reports from the Society of Cardiovascular Magnetic Resonance (SCMR), and data from a nationwide survey of CMR centers were used. Medicare claims for CMR studies from 2019 were compiled by the Moran Company. Surveys designed to collect data on center-specific characteristics were sent to 155 CMR centers identified through SCMR email listserve and Medicare claims data. Survey responses were reviewed to ensure only one response was captured from each center. Results: A total of 592 imaging centers were included in the Moran report and 112 unique centers responded to the survey. Of the centers included in the report, 47% billed for less than 10 of the most frequent study (CMR for morphology w/ dye) in 2019. The total density of CMR centers was 15.6 centers per million U.S. Medicare Part B beneficiaries. CMR centers are more dense in geographic areas of lowest socioeconomic disadvantage (based on the Area Deprivation Index), low poverty, and lowest percent of people lacking health insurance. Sixty-eight percent of survey responders were cardiologists, and 28% were radiologists. Seventy-two percent of centers reported performing 81-100% of their CMR exams in an academic healthcare system. Centers performing &gt;500 scans per year had an average of 19 years of experience, whereas centers performing &lt;50 scans had an average 3.5 years’ experience. The most common response for approximate patient wait time for CMR was 2 weeks to 1 month (45% of responses). Conclusions: Although CMR volume is increasing in the U.S., CMR access continues to demonstrate marked geographic variability. While almost half of centers are performing just a handful of scans annually, the greatest volumes are noted in well-established programs with years of experience. Identification of specific barriers to CMR access will be useful for future advocacy efforts and quality improvement initiatives.
Abstract 17671: Comparative Analysis of Warfarin and Direct Oral Anticoagulants for the Treatment of Left Ventricular Thrombus
Authors: Haig Pakhchanian, Spencer Carbone, Nakul Ganju, Rahul Raiker, Aseem Balhara
Journal: Circulation (2023)

Introduction: This study aims to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in the treatment of left ventricular thrombus (LVT). Warfarin has been shown to be an effective treatment in mitigating thrombotic events; however, numerous limitations exist, including the need for frequent monitoring and increased risk of side effects. Despite this, insight into DOAC use for the treatment of LVT remains limited. Thus, this study seeks to investigate the safety and efficacy of DOACs as a potential alternative to warfarin for the treatment of LVT. Hypothesis: DOACs decreases the risk of adverse events compared to Warfarin in patients with LVT. Methods: A retrospective cohort study was conducted using a federated realtime database called TriNetX which is comprised of over 100 million patient records. ICD-10 diagnostic codes and national drug codes were used to stratify adults by warfarin or DOAC treatment within 3 months of an initial LVT diagnosis. A 1:1 matched propensity score analysis was conducted, adjusting for comorbidities and demographics, to calculate adjusted Risk Ratios (aRR) with 95% CI. 90-day risk for mortality, stroke, need for blood transfusion, hemorrhage, and arterial embolism &amp; thrombosis were examined. Results: In a matched sample of 11,206 patients in each cohort, patients with LVT who took warfarin within 3 months of initial diagnosis is at higher risk for stroke (aRR[95%CI]=1.44(1.34,1.55)], need for blood transfusion [1.29(1.11,1.51)], hemorrhage [1.56(1.35,1.8)], and arterial thromboembolism [1.28(1.13,1.45)] than LVT patients who took a DOAC. Risk for death was non-significant between cohorts. Conclusions: The findings from this large electronic medical record patient cohort establish higher rates of adverse events for patients with LVT treated with warfarin versus DOAC, with no statistically significant difference in therapeutic efficacy.
Abstract 11322: Comparative Outcomes of Impella and Intra-Aortic Balloon Pump for Left Ventricular Unloading Among Patients With Cardiogenic Shock on Veno-Arterial Extracorporeal Membrane Oxygenation
Authors: Ilhwan Yeo, Rachel Axman, Daniel Y Lu, Dmitriy N. Feldman, Jim W Cheung, Robert M Minutello, Maria G Karas, Erin M Iannacone, Ankur Srivastava, Natalia I Girardi, Yoshifumi Naka, Shing-chiu Wong, Luke K Kim
Journal: Circulation (2023)

Background: Cardiogenic shock (CS) is associated with high morbidity and mortality. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used for patients with CS. Although Impella or Intra-aortic balloon pump (IABP) is frequently used for left ventricular (LV) unloading for increased afterload during VA-ECMO therapy, there are scarce comparative outcomes data for these devices. Aims: To compare short-term outcomes of Impella and IABP in patients on VA-ECMO for CS. Methods: Using the Nationwide Readmissions Database between 2016 and 2020, we analyzed outcomes of CS patients requiring VA-ECMO based on multivariable regression and propensity score methods. Results: Of 15,980 patients on VA-ECMO, IABP and Impella were used in 19.4% and 16.4% patients, respectively. The proportion of patients managed with Impella for LV unloading significantly increased from 2016 to 2020 (6.5% vs. 25.8%; P-trend&lt;0.001). In-hospital mortality was higher in Impella group (54.8%) compared with ECMO only (50.4%) and IABP (48.4%) groups. After adjustment, LV unloading using IABP vs ECMO only was associated with lower in-hospital mortality (OR, 0.83; 95% CI, 0.70-0.98). LV unloading using Impella vs ECMO only had similar in-hospital mortality (OR, 1.09; 95% CI, 0.91-1.31) but was associated with more bleeding (OR, 1.21; 95% CI, 1.04-1.41) and more acute kidney injury (AKI) requiring hemodialysis (HD) (OR, 1.42; 95% CI, 1.13-1.77). LV unloading with Impella vs IABP was associated with greater risk of AKI requiring HD (OR, 1.49; 95% CI, 1.13-1.97), higher in-hospital mortality (OR, 1.32; 95% CI, 1.10-1.60), and high 40-day mortality (HR, 1.25; 95% CI, 1.17-1.32). Conclusions: LV unloading using Impella, compared with IABP, was not associated with improved survival at 40 days in patients treated with VA-ECMO for CS, but was associated with increased adverse events. These findings suggest a need for further studies to guide clinical practice of LV unloading in CS.
Abstract 13509: Cardiovascular Outcomes in Metabolically Healthy Obese Asian-American Population Insights From a National Inpatient Sample
Authors: Avilash Mondal, BONEY LAPSIWALA, Ayodya R Perera, Pratik Bharat Rajpopat, Athri Kodali, Venkata Balaji Chenna, Amritha Nair, Valeriia Iermolenko, Rohini Bhuvaneshwari Gurumoorthy, Brinda Desai, Subramanian Gnanaguruparan, Rupak Desai
Journal: Circulation (2023)

Background: Cardio-metabolic risk factors usually predict major adverse cardio and cerebrovascular events (MACCE). However, outcomes in young metabolically healthy obese (MHO) Asian Americans (AA) have not been studied yet. Methods: Using the National Inpatient Sample (2019), we identified hospitalizations among young obese AA [aged 18-44] to obtain propensity-matched MHO+ and MHO- cohorts. Multivariable regression analyses were performed after controlling baseline demographic and comorbid variables to assess the risk of MACCE, including all-cause mortality, acute myocardial infarction, cardiac arrest, and stroke. Multivariable predictors of MACCE were also analyzed. P &lt;0.05 was statistically significant. Results: Of total 327,065 young AA hospitalizations, 25,470 were obese. Propensity-matched cohorts of MHO+ (n=14,200) and MHO-(n=14,200) were comparable for demographics (Median age 32 years, females 85.9% vs 84.8%). After adjusting for baseline demographics and comorbidities, the odds of MACCE (aOR 0.98, 95%CI 0.70-1.37, p=0.886) were higher, and ACM (aOR 1.26, 95CI% 0.4-3.99, p=0.690) was lower in MHO+ compared to MHO- group however, it was not statistically significant. MHO patients also had higher rates for MACCE among males (OR 10.18, 95%Cl 3.39-30.53, p &lt;0.001), drug abusers (OR 2.87, 95%Cl 1.05-7.86, p=0.04), cancer (OR 9.70, 95%Cl 2.14-44.01, p =0.003) and congenital circulatory anomalies (OR 21.77, 95Cl 4.07-116.60, p &lt;0.001). Conclusion: Obese AA population without cardiometabolic risk factors define a subgroup of at-risk population with males, drug abusers, cancers, and congenital abnormalities pose an increased risk of adverse cardio and cerebrovascular events. Targeted interventions, early risk stratification, and preventive measures are warranted in these populations.
Abstract 17965: Hypertension Cascade and Social Determinants of Health in Women of Reproductive Age
Authors: Faith E Metlock, Biruk Teshome, Oluwabunmi V Ogungbe, Yaa A Kwapong, Thomas Hinneh, Garima Sharma, Yvonne Commodore-Mensah
Journal: Circulation (2023)

Introduction: Studies examining hypertension (HTN) among women of reproductive age (18-44 years) are sparse. We sought to evaluate HTN awareness, diagnosis, treatment, and social determinants of health among women aged 18-44 years, in a national registry. Methods: We analyzed cross-sectional data from participants enrolled in the American Heart Association Research Goes Red (RGR) Registry, an online platform powered by Verily, who responded to the Project Baseline and RGR enrollment questionnaires. HTN outcomes were examined as self-report awareness of blood pressure (yes/no), HTN diagnosis (yes/no), and current HTN medication use (yes/no). Multinomial logistic regression models were used to assess the association between HTN cascade outcomes and social determinants of health, adjusting for age. Results: In a sample of 2,422 adult women (mean age 36 ± 6 years); non-Hispanic Black women were 3-times more likely have HTN (adjusted Odds ratio [aOR] 3.08; 95%CI 1.67-5.66) and be treated (aOR 3.21; 95%CI 1.67-6.03) compared to non-Hispanic White women ( Table ). The odds of HTN prevalence were higher (aOR 1.82; 95%CI 1.11-2.94) and HTN awareness lower (aOR 0.62; 95%CI 0.39-0.98) among Hispanic women compared to non-Hispanic White women. Compared to college graduates, high school graduates had 43% lower odds of HTN awareness, 85% high odds of HTN diagnoses. Persons with lower income were more likely to have HTN diagnoses and treatment and less likely to be aware. Conclusions: Social determinants of health including race, education and income were associated with HTN cascade outcomes. Tailored public health interventions and policies for improving HTN outcomes among women of reproductive age must address social needs.