tbuckley/cabot-search huggingface dataset:
Abstract 4147720: Dual Inhibition of Glutaminolysis and Pyruvate Carboxylase Attenuates Pulmonary Arterial Hypertension
Authors: Mathews Valuparampil Varghese, Joel James, Dinesh Bharti, Maki Niihori, Olga Rafikova, Ruslan Rafikov
Journal: Circulation (2024)

Introduction: Pulmonary arterial hypertension (PAH) is a serious condition that impacts the lung vasculature and has diverse underlying factors. Previous research has shown that mitochondrial dysfunction (MD) significantly contributes to PAH; however, the mechanisms remain unclear. Our recent findings indicate that in PAH, anaplerosis enhances the TCA cycle in pulmonary vascular cells, compensating for MD. Hypothesis: We hypothesize that inhibiting anaplerosis by targeting pyruvate carboxylase (PC) and glutaminolysis (GLUD1) in early PAH can prevent metabolic changes and pulmonary vascular remodeling. Methods: PAH was induced in female SD rats using Sugen/Hypoxia (Su/Hx). Anaplerosis inhibitors-phenylacetic acid (PAA), a PC inhibitor, at 20 mg/kg every other day (i.p.), and R162, a GLUD1 inhibitor, at 30 mg/kg daily (i.p.) were initiated after the right ventricular systolic pressure (RVSP) reached above 70 mmHg at week-two and continued for three weeks. Results: Hemodynamics in Su/Hx showed a PAH phenotype with increased RVSP. However, inhibiting anaplerosis reduced RVSP (111.10±3.59 mmHg to 45.87±2.202 mmHg, p&lt;0.001), Fulton Index (0.59±0.017 to 0.45±0.024, p&lt;0.001), and myocardial contractility (Max dP/dt 4511±196.9 mmHg/s to 2403.63±123.7 mmHg/s, p&lt;0.001). Our PAH model showed increased glycolytic flux with the activation of HK1 (p&lt;0.001) and PKM1 (p&lt;0.05). Increased glycolysis was found to shift to the pentose phosphate pathway via myo-inositol oxygenase (p&lt;0.001), generating ROS in the early PAH model. This leads to mitochondrial dysfunction with a reduction in complex-II (p&lt;0.05) expression and activation in the glycerophosphate shuttle with increased GPD2 (p&lt;0.001). These mitochondrial and redox imbalances trigger the endo-mesenchymal transition, leading to vascular remodeling in the late PAH model. Furthermore, the increased proliferative demand shifts the metabolism towards anabolism with NTX1 activation (p&lt;0.05), leading to proliferative signaling such as Akt (p&lt;0.01) and STAT3 (p&lt;0.05). Remarkably, inhibiting anaplerotic pathways with combined PAA and R162 therapy in the Su/Hx PAH model significantly attenuated metabolic dysfunction and prevented proliferative signaling, thus averting lung vascular remodeling. Conclusion: Our research indicates that inhibiting both pyruvate carboxylase and glutaminolysis-driven anaplerosis is a promising therapeutic approach for addressing vascular remodeling in PAH.
Abstract 4147493: Association Between Diabetes and 5-year Mortality and Major Amputation Outcomes After Revascularization in Chronic Limb-threatening Ischemia
Authors: Santiago Callegari, Jacob Cleman, Mufti Rahman, Abhinav Aggarwal, Kim Smolderen, Carlos Mena-Hurtado, Gaelle Romain
Journal: Circulation (2024)

Introduction: Diabetes affects over 60% of patients with chronic limb-threatening ischemia (CLTI). The impact of diabetes mellitus (DM) in long-term outcomes after lower-extremity bypass (LEB) or peripheral vascular interventions (PVI) remains unclear. We aim to assess the association between DM and 5-year all-cause mortality and major amputation after LEB vs. PVI for CLTI. Methods: Patients with CLTI undergoing LEB or PVI between 2014-2019 were abstracted from the Vascular Quality Initiative registry and stratified by DM status. Mortality and major amputation outcomes were derived from Medicare claims data. Patients in LEB vs. PVI groups were 1:1 propensity matched based on 13 preprocedural variables. The 5-year cumulative incidence of mortality by revascularization group and DM status was assessed with Kaplan-Meier and the risk in patients with DM vs. no DM by revascularization group (i.e., interaction DM status*revascularization group) was tested using Cox proportional hazard regression model. The Aalen-Johansen method and Fine-Gray model assessed the 5-year cumulative incidence and interaction between DM status and revascularization accounting for the competing risk of mortality. Results: A total of 4,210 patients (mean age 70.9 ±10.9, 30.7% female) were included of whom patients with DM were 65.7% and 58.8% of the PVI and LEB groups, respectively. Mortality cumulative incidence at 5-years was higher for DM vs. no DM in PVI (65.9% vs 59.5%; p=0.022) and LEB (59.3% vs 50.4%; p=0.003), with non-significant interaction for DM status (p =0.616). Amputation risk at 5 years was higher for DM vs. no DM for PVI (29.0% vs 14.3%; p&lt;0.001) and LEB (29.0% vs 16.3%; p&lt;0.001), with non-significant interaction for DM status (p =0.744). Conclusion: Mortality and major amputation risk at 5 years after revascularization for CLTI was higher for patients with DM vs. no DM regardless of the type of revascularization, with 3 out of 5 patients deceased and 1 out of 3 with a major amputation at 5 years. Shared decision-making and life expectancy discussions are needed for planning a definitive revascularization strategy.
Abstract 4147046: <u>Trends in Stroke-Related Mortality in Hypertensive Patients Aged 65 and Older in the United States: Insights from the CDC WONDER Database</u>
Authors: Muhammad Abdullah Naveed, Ahila Ali, Sivaram Neppala, MUHAMMAD KASHAN, Rabia Iqbal, Bazil Azeem, Muhammad Omer Rehan, Faiza Ashfaque, Huzaifa Ansari, Himaja Dutt Chigurupati, Timir Paul
Journal: Circulation (2024)

Background: Stroke is one of the leading causes of death for older individuals with hypertension. This research investigates the variations in stroke mortality rates and trends among 65-year-old hypertension patients in the US from 2000 to 2020. Methods: The CDC WONDER database's mortality data from 2000 to 2020 was used for a retrospective analysis. Average Annual Percentage Change (AAPC) and Annual Percent Change (APC) were used to evaluate trends and produce age-adjusted mortality rates (AAMRs) per 100,000 people. Data was stratified by year, sex, race/ethnicity, and geographical regions. Results: Between 2000 and 2020, 598,341 deaths among individuals 65 years of age or older in the United States were related to stroke due to hypertension. Most occurred in nursing homes/long-term care facilities (36.7%). The overall AAMR for stroke in hypertension-related deaths dropped from 86.6 in 2000 to 51.8 in 2020, with an AAPC of -2.86 (95% CI: -3.18 to -2.61, p &lt; 0.000001). Between 2000 and 2012, the AAMR had a considerable reduction (APC: -2.30, p &lt; 0.000001). Subsequently, from 2012 to 2018, there was a more dramatic decrease (APC: -6.85, p &lt; 0.000001) than a notable rise (APC: 6.45, p = 0.024) from 2018 to 2020. Older women had higher AAMRs than older men (women: 66.5; men: 60.1). Both sexes experienced decreases, with the decline more prominent in women (women: AAPC: -3.20, p &lt; 0.000001; men: AAPC: -2.22, p &lt; 0.000001). There were notable racial differences: Black people had the highest AAMRs (31.0), followed by White people (21.8), American Indians and Alaska Natives (18.6), Asians and Pacific Islanders (12.9), and Hispanics (12.5). All racial groups experienced decreases in AAMRs, most pronounced in Asians (AAPC: -4.62, p &lt; 0.000001). Geographically, Massachusetts had the lowest (36.3), and Mississippi had the highest (117.7) AAMRs. The Western region had the highest average AAMR (71.8), while nonmetropolitan areas exhibited higher AAMRs than metropolitan areas (nonmetropolitan: 25.9; metropolitan: 20.7). Conclusion: The study uncovers significant variations in mortality rates among elderly individuals in the US due to stroke and hypertension. The recent uptick emphasizes the necessity for targeted efforts to tackle these disparities and improve the health outcomes of affected communities.
Abstract 4146712: Prediction of Thrombosis in Coronary Artery Aneurysms Following Kawasaki Disease Using a Deep Learning Survival Approach
Authors: Cedric Manlhiot, Audrey Dionne, Michael Portman, Nagib Dahdah, Michael Carr, Manaswitha Khare, Ashraf Harahsheh, Seda Tierney, Michael Khoury, Geetha Raghuveer, Kevin Harris, Kambiz Norozi, Therese Giglia, Sean Lang, Wadi Mawad, Brian McCrindle
Journal: Circulation (2024)

Background: Prediction of thrombosis of coronary artery (CA) aneurysms in children with Kawasaki disease (KD) is challenging both because risk is determined by the interplay of complex anatomical, physiological and pharmacological factors and because of the rarity of events. Methods: We used data from 483 patients with at least one giant CA aneurysm (z&gt;10) and enrolled in the International Kawasaki Disease Registry to train and evaluate the performance of a deep learning survival (DeepSurv) algorithm predicting CA thrombosis over time. Outcomes were predicted separately for each CA branch. Each patient’s total follow-up duration was divided into epochs; new epochs were created with any new echocardiogram, change in thromboprophylaxis (either antiplatelet or anticoagulation) or outcome. Data (absolute aneurysm size, z-score and architecture) from the most recent echocardiogram were used at the start of each new epoch. Censoring was done on the last day of the epoch or date of last follow-up for the last epoch. Three-fold cross-validation was used to estimate model performance. SHAP analysis was used to calculate variable importance. Results: Average duration of follow-up was 4.2 years per patient; 87 (18%) patients had thrombosis during the follow-up period. The prediction model for thrombosis identified a high-risk group of epochs (28%). The high-risk epochs had a substantially greater incidence rate (5.1; 95%CI: 3.8-6.7) vs. 0.5 (95%CI: 0.4-0.7) events/100 patient-years, p&lt;0.001) and rate ratio (9.8; 95%CI: 6.3-15.4, p&lt;0.001). SHAP analysis identified critical features in predicting thrombosis, including larger aneurysm size, irregular aneurysm shape, recent change in thromboprophylaxis and, for those events diagnosed in the acute phase of the disease, immunosuppression and degree of inflammation. Events missed by the prediction algorithm were most often associated with rapid changes in CA aneurysm size during the acute phase of KD. Conclusion: A deep learning survival approach can be used to combine multiple dimensions of risk into a comprehensive, time-dependent, prediction model for thrombosis. This model identified a group of situations for which patients may be at substantially higher risk of developing a clot and where enhanced thromboprophylaxis should be considered. Particular attention should be paid to patients with large, irregular aneurysms, especially in hyperinflammatory contexts and when changing thromboprophylaxis regimen.
Abstract Sa102: Does Benefit of An Advanced Airway Depend on Initial Rhythm? A Secondary Analysis of the Pragmatic Airway Resuscitation Trial
Authors: Kianna Eurick-Bering, Henry Wang, David Berger, Robert Swor, Graham Nichol, Ahmed Idris, Mohamud Daya, Jestin Carlson
Journal: Circulation (2024)

Background: About 80 percent of patients with out-of-hospital cardiac arrest (OHCA) present with a non-shockable initial rhythm (asystole or pulseless electrical activity (PEA)), which is associated with lower survival. Advanced airway management and oxygen delivery are important OHCA interventions, but their impact based on different presenting rhythm groups are unknown. Our objective was to determine if advanced airway strategy is associated with outcomes in shockable, PEA and asystolic OHCA. Methods: We performed a secondary analysis of data collected from the Pragmatic Airway Resuscitation Trial (PART), which assigned adult OHCA to a strategy of either endotracheal intubation (ETI) or laryngeal tube (LT) for initial airway management. We stratified patients by initial cardiac rhythm: shockable (ventricular fibrillation/tachycardia, AED shock), PEA or asystole. We excluded AED non-shockable and unknown rhythms. The primary outcome was 72-hour survival. Secondary outcomes included return of spontaneous circulation (ROSC) at emergency department arrival, survival to hospital discharge, and survival with good neurological function (modified Rankin score ≤3). We used general estimating equations to determine the associations between airway strategy and outcomes, stratified by initial rhythm and adjusted for age, sex, witnessed status, and bystander CPR. Results: There were 3,004 patients in the parent trial of which 2,847 were included in this analysis. Of these 575 were shockable, 671 were PEA, and 1,601 were asystole. Compared with ETI, LT airway was not associated with improved 72-hour survival in shockable rhythms (OR adj 1.30 (0.91-1.67)), PEA (OR adj 0.97 (0.65-1.45)), or asystole (OR adj 1.13 (0.79-1.64)). Similarly, we noted no significant difference by airway strategy for secondary outcomes of ROSC, survival to discharge, and survival to discharge with good neurological function. Conclusion: Prehospital advanced airway management strategy (ETI vs. LT) was not significantly associated with outcomes regardless of initial rhythm.
Abstract 4147361: SCAI stage transition after axillary mechanical circulatory support in heart failure cardiogenic shock
Authors: Aarti Desai, Cetin Alak, Shriya Sharma, Caitlyn Luce, Jose Ruiz-Morales, Parag Patel, Rohan Goswami
Journal: Circulation (2024)

Background: The Society for Cardiovascular Angiography and Interventions (SCAI) staging system is a crucial tool for categorizing cardiogenic shock (CS) and guiding interventions. SCAI staging is traditionally static and may not capture dynamic changes. We evaluated the impact of axillary mechanical circulatory support and SCAI stage transition in patients with CS supported until heart transplantation. Methods: A retrospective study was conducted on patients with Impella support as bridge to transplant. Hemodynamic and vasoactive support parameters were collected and SCAI stage recorded at baseline and after 72 hours. Results: 36 patients were included in the analysis. The median age was 61 (52 – 68) with an EF of 19% (15-26%) (Figure 1). Before Impella placement, the distribution of patients across SCAI stages was as follows: 19 patients in SCAI B, 8 patients in SCAI C, and 9 patients in SCAI D. After 72 hours of Impella support, 7 patients initially classified as SCAI C transitioned to SCAI B with one deteriorating to SCAI D (Figure 2). Patients in SCAI D showed notable improvement, with 8 out of 9 patients transitioning to SCAI B. For patients initially SCAI B, RA changed from 10 to 11 mmHg, and PCWP decreased from 23 to 17 mmHg. The Fick CI increased from 2.53 to 3.02 L/min/m 2 (p=0.04), and the vasoactive inotropic score (VIS) decreased from 7.5-5.0 (p=0.05). In patients initially classified as SCAI C, RA pressure decreased from 13 to 8 mmHg, and PCWP reduced from 32 to 30 mmHg. The Fick CI improved from 1.79 to 2.61 L/min/m 2 (p&lt;0.001), while the VIS decreased from 9.2 to 6.3 (p=0.004). For those initially in SCAI D, RA pressure reduced from 8 to 5 mmHg, and PCWP decreased from 27 to 18 mmHg. The Fick CI increased from 1.55 to 2.67 L/min/m 2 (p=0.002), and the VIS was notably reduced from 4.75 to 3.8 (p=0.36). All 36 patients survived to heart transplantation without major pre-transplant complications. Conclusion: SCAI stage C-E mortality ranges from 25 – 50% or worse. Implementing Impella 5.5 support reduced SCAI severity and may be associated with improved survival in HFCS. We demonstrated lower VIS after Impella 5.5 and a 100% event free survival to heart transplantation despite a 25% baseline SCAI D cohort. Larger data should be evaluated to assess this trend.
Abstract 4146996: Trends in the Management and Outcomes of ST Elevation Myocardial Infarction with Cardiogenic Shock in Older Adults: Insights from US National Database
Authors: Manoj Kumar, Nso Nso, Mark Ricciardi, Qamar Arman
Journal: Circulation (2024)

Background: Due to increased life expectancy, there is increasingly high prevalence of myocardial infarction (MI) in older adults (age ≥75 years). Older adults tend to receive less guideline recommended treatment for MI due to associated frailty. We compare the management and outcomes in older adults with ST elevation myocardial infarction (STEMI) and cardiogenic shock (CS) as compared to adults age &lt;75 years. Methods: Nationwide Readmissions Database (2016-2021) was analyzed to study patients with STEMI-CS. Cohort was stratified by age. Mahalanobis Distance Matching within the Propensity Score Caliper was used to match older adults (age ≥75 years) with patients age &lt;75 years. Inverse Probability weighting (IPW) was utilized, and Pearson’s chi-squared test was applied to the PSM-2 matched cohorts to compare outcomes. Results: Among 177,874 hospitalizations of STEMI-CS, more than half (57.7%) were older adults (age ≥75). After propensity matching (N: 55,855 in each group), older adults were less likely to receive PCI (60.6% vs. 62.2%, aOR: 0.93 [95% CI], p &lt;0.001) and had a higher mortality (45.2% vs. 33.9%, aOR:1.75 [95%CI], p &lt;0.001) as compared to patients age &lt;75 years. From the year 2016-2021, mortality of STEMI-CS has remained unchanged for older adults (mean: 43%) (p-trend &gt;0.05). Moreover, an alarming decline for PCI for older adults was also noted (59.4% to 44%, p-trend&lt;0.001). Conclusion: Older adults are less likely to receive PCI and have a higher mortality compared as to patients age &lt;75 years when presenting with STEMI and cardiogenic shock. Focused initiatives are needed to improve STEMI care in older adults.
Abstract 4147288: Social determinants and healthcare utilization among adults with hypertrophic cardiomyopathy: data from the All of Us Research Program
Authors: Milla Arabadjian, Jielu Zhang, Donglan Zhang, Shahidul Islam
Journal: Circulation (2024)

Background: Individual-level social determinants of health (SDoH) and healthcare utilization (HCU) are understudied among adults with hypertrophic cardiomyopathy (HCM). Objective: To examine SDoH and HCU among adult participants in the All of Us Research Program, who have a diagnosis of HCM. Methods: We conducted a cross-sectional analysis All of Us Research Program data, overall, stratified by race and ethnicity, and by self-identified gender. Eligible individuals included those with an ICD-9, or ICD-10 diagnostic codes for HCM. We used chi square tests and t-tests to examine differences in SDoH and HCU among the study population. Results: The sample was N=1,110 (51% women, 21% non-Hispanic Black [NH] adults, 11% Hispanic adults, 39% with obstructive HCM). Median [interquartile range] was 69 years [59;77]. Seventeen percent had Medicaid, 38% among Hispanic adults, vs 35% among NH Black adults and 6.8% among NH White adults, p&lt;0.001. Medicaid % was similar among women and men. The lowest education level (high school or below) was among Hispanic adults, 81%, vs 78% among NH Black adults, and 38% among NH White adults, p&lt;0.001, and among women 56%, vs men, 46%, p&lt;0.001. Seventy-nine percent of Black adults had a yearly income &lt;$50,000, vs 73% among Hispanic adults, and 35% among NH White adults, p&lt;0.001. Fifty-four percent of women had this income vs 41% of men, p&lt;0.001. HCU data was available for 50% of the sample. There were no racial or ethnic differences related to usual place of care or number of health visits over the last year. However, 27% of NH Black adults reported not being able to afford their prescriptions, vs 11% among Hispanic adults, and 9.4% among NH White adults, p=0.003. Women were more likely to delay care due to work, 7.5% vs men, 2.9%, p=0.023, and caregiving responsibilities, 4.5%, vs men, 0.9%, p=0.032. Geospatial analysis found that most participants resided at least 28 miles away from an HCM specialty center. Conclusions: This analysis identified individual-level SDoH and HCU patterns among a diverse cohort of community-dwelling adults with HCM. Findings may inform future intervention targets and intervention strategies to improve access and care for individuals with HCM.
Abstract 4146711: A meta-analysis of myocardial recovery and its associated factors in advanced heart failure with left ventricular assist device
Authors: Elfatih Hasabo, Burce Isik, Mohamed Bakr, Mohammed Mahmmoud Fadel Allah, Dina Neiroukh, Mahmoud Nosir, Cagri Ayhan, Sherif Sultan, Kadir Caliskan, OSAMA SOLIMAN
Journal: Circulation (2024)

Introduction: Patients with advanced heart failure use left ventricular assist devices (LVAD) to improve their outcomes and enhance the reverse remodeling of the heart. There has been no previous meta-analysis on the percentage or predictors of myocardial recovery after LVAD according to the device strategy. This study aims to find the pooled percentage and determinants of myocardial recovery after LVAD. Methods: A systematic search was done in PubMed, Scopus, Web of Science, Embase, and Cochrane from inception to April 2024. We used relevant keywords to include the studies that reported the percentage of people who have achieved myocardial recovery after LVAD. The percentage of participants using LVAD and achieved myocardial recovery was extracted and pooled results were stratified according to the device strategy. RevMan 5.4 was used for the meta-analysis. Results: We included 30 studies comprising 38708 patients with various LVADs used among the participants. Across the studies, multiple terms for myocardial recovery were used, most commonly being device explant following myocardial recovery and achieving left ventricular ejection fraction (LVEF) ≥40% after using LVAD. The overall pooled percentage of people who achieved myocardial recovery was 4.61% (95% CI [3.77, 5.45]), and the result was heterogeneous (I2 = 93%, p &lt;0.00001). The percentage of myocardial recovery in patients implanted as a bridge to recovery (BTR) was 24.8%, 11.1% for a bridge to transplant (BTT) and 2.9% for mixed device strategy (Figure 1). Shorter duration of heart failure, female gender, younger age, absence of implantable cardioverter-defibrillator (ICD), and low left ventricular end-diastolic diameter (LVEDD) were the most cited factors associated with myocardial recovery. Conclusion: Myocardial recovery following LVAD is low and was found to be high in patients implanted for BTR. Several factors have been identified as potential predictors of myocardial recovery in patients on LVAD therapy. Further action should be taken to improve the recovery among this population.