tbuckley/cabot-search huggingface dataset:
Abstract 4139918: Myocardial Transcriptomics Differentiates Decompensated, Compensated, and Healthy Right Ventricular Samples in End Stage Heart Failure
Authors: Jonah Garry, Giovanni Davogustto, Vineet Agrawal, Evan Brittain
Journal: Circulation (2024)

Introduction: Myocardial transcriptional changes in the right ventricle (RV) during stress and failure are poorly understood. We hypothesized that myocardial transcriptomic signatures would differ among decompensated (d-RV), compensated (c-RV), and healthy RV (h-RV) myocardium. Methods: We obtained RV free-wall myocardial samples from pts undergoing transplant for end-stage HF (n=33). Control samples were obtained from unused donor hearts. We defined d-RV by pulmonary arterial pulsatility index &lt;/= 2.0 (10/33, 30%). We performed RNA-seq using the Illumina NovaSeq6000 with pair-wise differential gene expression using DESeq2 (FDR &lt;0.05) and Gene Set Enrichment Analysis (GSEA) using WebGestalt to identify differentially regulated pathways (FDR &lt;0.1). Results: Controls (n=8) were 44 years [IQR 39-57] and 50% male. HF pts were 53 years [44-61], 63% male, 13 ischemic and 22 non-ischemic, with median LVEF 21% (IQR 16-28%). Principal component analysis demonstrated distinct expression for h-RV vs c-RV and d-RV, but poorly differentiated between c-RV and d-RV ( Figure 1A ). Volcano plots for pairwise comparisons with differentially expressed genes (DEGs) are displayed in Figure 1B-D . Notable upregulated genes in d-RV and c-RV vs h-RV included NPPA, NPPB, and MYH6. Of the 4171 DEGs of d-RV vs h-RV, 3625 were also identified comparing c-RV vs h-RV. There were 39 DEGs differentiating d-RV vs c-RV. GSEA identified increased transcription of immune pathways, metabolism, and protein synthesis related pathways in c-RV and d-RV vs h-RV (Figure 2A ). c-RV vs d-RV featured increased protein synthesis and decreased immune system and catabolism related pathways ( Figure 2B ). Conclusions: The RV response to stress in end-stage HF features transcriptional increases in immune pathways and protein synthesis along with metabolic changes in fatty acid synthesis, insulin signaling, and steroid biosynthesis. These findings warrant further mechanistic investigation of the implicated pathways.
Abstract 4139850: Demographics and Regional Trends of Chronic Renal Failure- and Heart Failure-related mortality in older adults: Insights from CDC-Wonder Database 1999-2020
Authors: Eman Ali, Hafsah Alim Ur Rahman, Muhammad Ahmed Ali Fahim, Huzaifa Ahmad Cheema, Adeel Ahmad, Wajeeh Rehman, Sourbha Dani
Journal: Circulation (2024)

Introduction: The incidence of Heart Failure (HF) has increased as the US population ages, with Chronic Renal Failure (CRF) being a common comorbidity and risk factor for mortality. This study aims to identify annual, gender, race, and geographical trends in CRF-related mortality in patients with HF for older adults. Methods: We used ICD-10 (International Classification of Diseases 10th Revision) codes to retrospectively analyze death certificate data from the Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research (CDC WONDER) database between 1999-2020 for patients ≥65 years old with concomitant HF and CRF. Age-adjusted mortality rates (AAMRs) per 100,000 people and Annual Percentage Change (APCs) and their respective 95% Confidence Intervals (CI) were also calculated for patient data grouped according to year, gender, race, and geography. Results: From 1999-2020, 425,854 deaths occurred from CRF and HF in patients ≥ 65 years. The overall AAMR was 46.1 (95% CI: 46 to 46.3), with the APC from 1999-2020 being 2.96 (95% CI: 1.84 to 4.32). Males reported higher AAMRs than females (overall AAMRs: 62.1 vs 36.2). Stratifying data by race revealed NH (Non-Hispanic) Black or African American to have the highest AAMR (62.2) followed by NH American Indian or Alaska Native (52.5), NH White (45.5) and Hispanic or Latino (37.2), with the NH Asian or Pacific Islander race having the lowest AAMR (30). According to the census region, the highest AAMRs were reported in the Midwest (54.3), followed by the West (45.1) and South (43.4), with the lowest AAMRs in the Northeast (42.3). Furthermore, Non-Metropolitan areas revealed higher AAMRs when compared to Metropolitan areas (54.4 vs 43.3). The states in the top 90 th percentile were Indiana, Kentucky, Minnesota, North Dakota, and West Virginia. They had AAMRs nearly double those in the bottom 10th percentile, such as Arizona, Hawaii, Nevada, and New Mexico. Conclusion: Trends in CRF- and HF-related mortality in older adults have varied from 1999-2020, with the highest AAMRs being reported in men, NH Black or African Americans, Non-Metropolitan areas, and in the Midwest. Strategies to target precipitating events are necessary alongside further investigations to explain the trend variations.
Abstract 4139909: Rural and Urban Patterns of Monitoring of Implanted Cardiac Devices in the US
Authors: Emily Zeitler, Weiping Zhou, Mark Creager, James O'Malley
Journal: Circulation (2024)

Background: Along with in-person (IP) monitoring, remote monitoring (RM) is recommended for patients with a cardiac implantable electronic device (CIED) to improve clinical outcomes. Hypothesis: Rurality will adversely impact the delivery of both RM and IP monitoring as part of comprehensive CIED care. Aims: To define and compare CIED monitoring patterns among patients with a CIED in rural and urban geographies. Methods: All Medicare fee-for-service beneficiaries (2011-2021) with history of CIED implantation were included based on relevant CPT codes. Demographic characteristics were reported by implant year and stratified by rurality based on beneficiary rural-urban commuting area code. All IP and RM events in the year following implant were tabulated based on CPT and ICD-9/10 procedure codes and similarly stratified by geography. Results: Approximately 23% of the de novo CIED implants (approximately 150,000/year) were among patients living in rural areas. The mean age was 79-80 years across the study period and was slightly higher (&lt;1 yr difference) in the urban group; the proportion of men was similar in each group (~57%). Comorbidity was high in both geographic strata throughout the study period, including hypertension (~94%), ischemic heart disease (~80%) and heart failure (~65%). In the year following implant, the proportion of patients with ≥1 IP monitoring event was stable and consistently greater among the urban than rural cohort (~81% vs ~78% in 2019) until 2020 when the proportion fell for both groups (75% vs 72%, respectively) (Figure). The proportion of patients with ≥1 RM event rose substantially over the study period (from 22% to 51% in the urban group and 28% to 50% in the rural group). Conclusions: Dramatic improvements in RM were observed among Medicare beneficiaries with a CIED in the last decade. Patients in rural areas were historically more likely to undergo RM than their urban counterparts, but this gap narrowed and equalized over time. By 2020, a decline in IP monitoring was accompanied by an increase of growth in RM in both urban and rural areas, possibly reflecting effects of the COVID pandemic on CIED care access.
Abstract 4140265: Single Cell Transcriptomics Unveils Novel Lung Capillary Endothelial Cell Populations and Their Crucial Roles
Authors: Joel James, Aleksandr Dekan, Dinesh Bharti, Mathews Valuparampil Varghese, Sedat Kacar, Maki Niihori, Olga Rafikova, Ruslan Rafikov
Journal: Circulation (2024)

Background: Understanding the intricate dynamics of lung microcirculation and capillary endothelial cells (ECs) is crucial for shedding light on both normal physiological processes and the pathogenesis of pulmonary diseases. Recent advancements in single-cell transcriptomics (scRNA-seq) have unveiled distinct lung EC populations, including aerocytes and general capillary cells (gCaps). Hypothesis: We hypothesized that gCaps demonstrate more extensive diversity than previously understood, marked by distinct molecular and functional profiles. Methods: We utilized scRNA-seq and computational analysis on enriched populations of lung ECs. The mitostress Seahorse assay was conducted to study metabolic function. Electric cell-substrate impedance sensing (ECIS) assessed cell growth, and the Matrigel assay evaluated angiogenic potential of isolated ECs. Results: scRNA-seq analysis identified five novel gCap populations, each with unique molecular signatures and functions. Notably, two populations characterized by the expression of ion transporters Scn7a (Na+) and Clic4 (Cl−) are crucial for establishing arterial-to-vein zonation and enhancing the capillary barrier. We identified "root" cells (Flot1+), exhibiting the highest G2M and S scores, essential for the mitotic regeneration and repair of neighboring ECs. Depletion of Flot1+ cells significantly impaired EC proliferation, highlighting their critical role in cell repair. Furthermore, we discovered that gCaps aiding in the venous transition were characterized by the expression of Lingo2. Additionally, we identified a population of detached gCaps marked by an elevated expression of Fabp4, metabolically active genes, and tip-cell markers, suggesting a key role in regulating angiogenesis. The Matrigel sprouting assay confirmed that Fabp4+ gCaps significantly contribute to angiogenesis. Metabolic assays indicated that both Clic4+ and Fabp4+ cells exhibited increased mitochondrial function. Finally, western blot analysis across various EC junction and signaling proteins in isolated gCaps showed significant heterogeneity, further illustrating the complex nature of these cell populations. Conclusion: Our study highlights the diverse roles and molecular signatures of lung capillary ECs, enhancing our understanding of their contributions to both normal lung function and pulmonary diseases. These insights also offer valuable direction for developing therapeutic strategies aimed at addressing cardiovascular disorders.
Abstract 4139940: Safety and Efficacy of Self-Expanding vs Balloon-Expandable Valves for Transcatheter Aortic Valve Replacement in Patients with Aortic Stenosis: A Systematic Review and Real-World Meta-Analysis
Authors: Abdul Hannan Siddiqui, Javeria Mansoor, Hashir Habib, Priya Devi, Mariyam Waheed, Priya Hotwani, Kashaf Saleem, Mukesh Kumar, Laksh Kumar, Syed Anas Hussain, Ahmed Bin Hassan, Abdul Moeed, Hala Najeeb, mahboob alam
Journal: Circulation (2024)

Background: There are two approved methods for transcatheter aortic valve replacement (TAVR) namely balloon-expandable valves (BEV) and self-expanding valves (SEV). While several randomized controlled trials (RCTs) have compared the efficacy of SEV and BEV, the generalizability of their findings is questioned. Therefore, to generate concrete evidence regarding the superiority between the two, we conducted this real-world meta-analysis to compare the clinical efficacy and safety outcomes of SEV vs BEV in patients undergoing TAVR for aortic stenosis (AS). Methods: MEDLINE, EMBASE, and Scopus were queried to shortlist studies including AS patients undergoing TAVR. Primary outcomes included 30-day and 1-year all-cause and cardiac mortality. Secondary outcomes were permanent pacemaker implantation (PPI), paravalvular leak (PVL), aortic regurgitation (AR), stroke, major vascular complications (MVC), major bleeding (MB), acute kidney injury (AKI), myocardial infarction (MI), length of stay (LOS), patient prosthesis mismatch (PPM), and atrial fibrillation (AF). A random effects meta-analysis was conducted to derive risk ratios and mean differences with corresponding 95% confidence intervals (CI). Results: Our meta-analysis included 38 real-world studies. No significant association was seen in 30-day (RR=1.13, P=0.15) and 1-year all-cause mortality (RR=1.04, P=0.55), and cardiac mortality (RR=1.28, P=0.12). SEV was associated with a higher risk of 30-day PPI (RR=1.61, 95% CI 1.28-2.02, I2 = 88%, P&lt;0.0001), mild PVL (RR=1.52, 95% CI 1.17-1.97, I2=76%, P=0.002), and moderate to severe PVL (RR=1.97, 95% CI 1.43-2.72, I2=51%, P&lt;0.0001). Patients in the SEV group experienced more statistically significant AR (RR=1.72, 95% CI 1.29-2.30, I2=27%, P=0.0002), and 30-day MVC (RR=1.1, 95% CI 1.02-1.2, I2=0%, P=0.02) when compared to the BEV group. No statistically significant association was established for stroke, MB, AKI, MI, LOS, PPM, and AF. Conclusion: Our real-world analysis showed that SEV increases the risk of PPI, PVL, AR, and MVC. However, all-cause and cardiovascular mortality were comparable between both groups. Our results confirm the conclusions drawn from RCTs, thus reassuring decision-makers that these findings can be extrapolated to real-world populations.
Abstract 4139555: Transitions Between Heart Failure States in Adult Patients with Congenital Heart Disease
Authors: Emily Zhang, Qiyu Wang, Yining Fan, Aihua Liu, Yi Yang, Ariane Marelli
Journal: Circulation (2024)

Background: The growing number of adult congenital heart disease (CHD) patients facing heart failure (HF) related complications after the age of 40 has become a major concern. There is a lack of data to capture the dynamic nature of HF progression across the adulthood, with the consideration of various contributing factors. This application of multistate models paves a promising way to accurately track health state changes, thus to provide data to inform surveillance and interventions to prevent disease progression, potentially improving personalized treatment plans for a significant patient population. Aims: This study aimed to (1) determine the expected time a patient remains in each HF state, based on predisposing factors; (2) evaluate the probabilities that, across different ages, a patient will either remain at the same state, transition to the next HF state, or die; (3) identify the risk factors of transitioning between health states related to HF among CHD patients. Methods: The dataset was derived from the Quebec CHD database which encompasses 137,493 patients, spanning 35 years of follow-up from 1983 to 2017. We constructed a multistate model to include 6 states: no HF history (0HF), having one (1HF), two (2HF), three (3HF) or more than four HF events (4+HF), and death. Each HF state transition was modeled by Cox proportional hazards regression using the same predictors, including sex, presence of severe congenital heart defects, and comorbidity history. Results: The study included 83,669 adult patients with CHD. Among them, 32,934 HF events and 16,348 deaths were observed during a total of 1,732,942 person-years of follow-up. With each HF occurrence, patients showed faster progression to subsequent HF events. Patients with severe CHD lesion had nearly two decades fewer HF-free years compared to those with non-severe lesions (Figure). Early age of initial HF increased the risk of additional HF events and mortality. Comorbidities such as diabetes and chronic kidney disease markedly reduced the duration that a CHD patient remains HF-free. Conclusion: The study findings highlight the need for early intervention and personalized treatment strategies in managing HF progression in CHD patients.
Abstract 4139892: Trends in ACS-Related Mortality in Older Adults in the United States from 1999 to 2020: An Analysis of Gender, Race/Ethnicity, and Geographic Disparities
Authors: Naima Khan, Madiha Salman, Arooba Ejaz, Bazil Azeem, M. Mujeeb Zubair, Eman Ali, Huzaifa Ahmad Cheema, Adeel Ahmad, Wajeeh Rehman, Asim Shaikh, Sourbha Dani
Journal: Circulation (2024)

Background and Purpose: Specific populations of older adults in the United States are experiencing worsening trends in the incidence and prevalence of acute coronary syndrome (ACS). This study examined trends in ACS-related mortality among older adults in the United States. Methods: The CDC-WONDER (Centers for Disease Control and Prevention Wide-ranging OnLine Data for Epidemiologic Research) database was used to track deaths due to ACS in adults aged ≥ 65 years from 1999 to 2020. Age-adjusted mortality rates (AAMRs) per 100,000 population were determined and stratified by year, sex, race/ethnicity, and geographic region. Joinpoint regression was used to analyze trends in AAMRs using annual percent change (APC). Results: Altogether, 3,017,769 deaths occurred due to ACS and the overall ACS-related AAMR was 327.5 from 1999 to 2020. Following an initial period of rapid decrease in mortality rates from 1999 to 2011 (APC: -5.98; 95% CI: -6.40 to -5.65), the rate of decline halved from 2011 to 2020 (APC: -3.02; 95% CI: -3.62 to -2.19). Men had consistently higher AAMRs (410.6) than women (267.8). In racial and ethnic groups, the Non-Hispanic (NH) Black or African American population had both the highest total AAMR (374.4) and was one of the two ethnicities that displayed increasing trends from 2018-2020 (APC: 4.74; 95% CI: 0.30 to 7.10). The second ethnic group with increasing trends was Hispanic or Latino (2018-2020 APC: 9.27; 95% CI: 3.22 to 13.16). Significant geographic disparities were observed, with nonmetropolitan areas having consistently higher AAMRs (433.5) than metropolitan areas (304.1). States in the top 90th percentile (District of Arkansas, Kentucky, Mississippi, Missouri, South Dakota, and Tennessee) had almost double the AAMRs than states in the bottom 10th percentile (Alaska, Colorado, Hawaii, Minnesota, Montana, and Nevada). Conclusion: Despite an overall decrease in mortality, the deceleration of decline since 2011is concerning. Men, NH Black/African American populations, and residents of nonmetropolitan areas displayed the highest burden of ACS-related mortality. Focused strategies are required to prevent and manage ACS in older adults to mitigate the rising levels of ACS-related mortality.
Abstract 4140178: Plasma Proteomic Biomarkers Are Associated With Physical Frailty In Heart Failure: A Propensity Score Matched Exploratory Study
Authors: Quin Denfeld, Noelle Pavlovic, Christopher Lee, Jon Jacobs, Mary Roberts Davis, Samantha Powell, Marina Gritsenko, Susan Joseph, Beth Habecker
Journal: Circulation (2024)

Background: Physical frailty is highly prevalent in heart failure (HF), but we lack an understanding of the underlying pathophysiology. Proteomics evaluation of plasma samples may elucidate potential mechanisms and biomarkers of physical frailty in HF. Purpose: To identify plasma proteomic biomarkers that are differentially expressed between physically frail and non-physically frail adults with HF. Methods: This was a secondary analysis of a subset of data and plasma samples from a study of frailty among patients with New York Heart Association (NYHA) Functional Classification I-IV HF. Physical frailty was measured using the Frailty Phenotype Criteria. Propensity score matching was used to match pairs of physically frail (n = 20) vs. non-physically frail (n = 20) patients on clinical characteristics. Plasma samples were processed using a sensitive liquid chromatography mass spectrometry platform, utilizing a multiplexed tandem mass tag-labeled quantitative proteomics approach. Differentially expressed proteins were quantified individually using paired t tests with associated log2 fold change of 0.3 and using Fisher’s combined p values. Results: The sample (n = 40) was 62.8±16.9 years old, 58% female, and 55% NYHA class III/IV. The log2 fold changes for each of the 2684 proteins were compared with the corresponding -log10 p-values in a volcano plot ( Figure ), which identified 27 proteins significantly different (10 downregulated and 17 upregulated with physical frailty). Of these, 7 proteins were differentially expressed across all three plexes: matrix metalloproteinase-14 was downregulated in frailty, and copine-1, low affinity immunoglobulin gamma Fc region receptor III-A and III-B, probable non-functional immunoglobulin kappa variable 2D-24, glutathione S-transferase Mu 1, and argininosuccinate lyase were upregulated in frailty. Conclusions: Proteomic biomarkers related to the immune system, stress response, and detoxification were differentially expressed between physically frail and non-physically frail adults with HF. Patients with HF who are physically frail appear to be in a state of chronic immune and stress response upregulation coupled with downregulation of cellular activation.
Abstract 4139790: Efficacy and Safety of Omecamtiv Mecarbil in Heart Failure with Reduced Ejection Fraction According to Age: the GALACTIC-HF Trial
Authors: Henri Lu, Brian Claggett, Gary Felker, John McMurray, John Teerlink, Marco Metra, Stephen Heitner, Rafael Diaz, Fady Malik, Muthiah Vaduganathan, Scott Solomon
Journal: Circulation (2024)

Background: Older age is associated with a high prevalence of comorbidities and worse cardiovascular (CV) outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Omecamtiv mecarbil (OM), a selective cardiac myosin activator, is relatively hemodynamically neutral with no known extra-cardiac effects, and thus may be well-tolerated in older individuals with comorbidities (e.g., low blood pressure or renal dysfunction). The safety profile and clinical benefits of OM across the age spectrum remain uncertain. Purpose: To assess the CV outcomes, treatment response and tolerability to OM according to age, in patients enrolled in the GALACTIC-HF trial. Methods: GALACTIC-HF was a randomized, double-blind clinical trial testing OM vs placebo in patients with symptomatic HF. Key eligibility criteria included an age between 18 and 85 years, elevated natriuretic peptides and a left ventricular ejection fraction (LVEF) ≤35%. We examined the treatment effect of OM vs placebo for the primary endpoint of CV death or first HF event (hospitalization or urgent visit for HF), in the overall population and severe HF subgroup (LVEF≤30%, New York Heart Association [NYHA] Class III/IV, HF hospitalization within 6 months), as well as safety outcomes according to predefined age groups (&lt;65 or ≥65). Results: A total of 8,232 patients (age 64.5±11.4 years, 54.5% ≥65 years, 21% women) were included. The rate of the primary outcome was 21.4 per 100py in age &lt;65 years and 28.8 per 100py in age ≥65 years. The treatment effect of OM for the primary outcome (hazard ratio [HR] 0.92; 95% confidence interval [CI] 0.86-0.99; p=0.025) was consistent in age groups (P interaction =0.73, Figure 1 Panel A ) and irrespective of age as a continuous variable (P interaction =0.19), after adjustment for treatment interactions with known modifiers of the effects of OM (LVEF and baseline atrial fibrillation status). In patients with severe HF, OM significantly reduced the risk of the primary outcome in both age &lt;65 years (HR 0.77; 95% CI 0.64-0.92) and age ≥65 years (HR 0.83; 95% CI 0.71-0.97; P interaction =0.72, Figure 1 Panel B ). The safety profile of OM was consistent irrespective of age (P interaction &gt;0.05 for all, Table 1 ). Conclusions: In GALACTIC-HF, older individuals were well-represented and faced higher risks of CV events. Treatment with OM was safe irrespective of age, and reduced the risk of CV death or first HF event across the age spectrum, especially in those with severe HF.