tbuckley/cabot-search huggingface dataset:
Abstract 4141719: Gender Differences in Bleeding Risk and Mortality Following Dual Antiplatelet Therapy Post-Percutaneous Coronary Intervention: A Meta-Analysis
Authors: Alhasan Saleh Alzubi, Mohammed S. Beshr, Ibrahem A. Beshr, Abdelrahman Farag Abdelwahed, Sarah Mohamed Alfaqaih, Maram Abuajamieh, Rana Hasen Shembesh, Arwi Omar Kara, Ahmed Elfaituri, Saifaleslam Jamal Elsahli, Muhammed Elhadi
Journal: Circulation (2024)

Background: Dual antiplatelet therapy (DAPT) is widely used following percutaneous coronary intervention (PCI), but it can be associated with bleeding events and adverse outcomes during therapy. This study aims to perform a gender-based analysis of the bleeding risk and mortality associated with DAPT following PCI. Methods: On May 15, 2024, we searched the following databases: PubMed, Embase and Cochrane. Our inclusion criteria included any trial or cohort that performed a gender-based analysis of bleeding and mortality outcomes in patients taking DAPT post-PCI. Our outcomes were all-cause mortality, cardiac mortality, and bleeding risk. Bleeding risk was assessed using the Bleeding Academic Research Consortium (BARC) classification, and Thrombolysis in Myocardial Infarction (TIMI) bleeding criteria. We used RevMan with a random-effects model to calculate the effect size, using odds ratios (OR) with a 95% confidence interval. Results: Out of the 1,865 articles searched, only 26 papers were eligible for inclusion and analysis. Nine were randomized controlled trials, and 17 were observational cohorts. The total number of patients was 267,986, of which 203,524 were male and 64,436 were female. There was no significant difference in cardiac mortality between males and females; the OR was 0.88 (95% CI: 0.71-1.08, P=0.22). All-cause mortality was reduced in males compared to females, with an OR of 0.81 (95% CI 0.71-0.92, p=0.002). The BRAC 2-5 classification was less likely in males compared to females, with an OR of 0.81 (95% CI: 0.70-0.94, p=0.005). Similarly, in the BRAC 3-5 classification, there was a significant lower probability of bleeding in male compared to female (OR 0.65, 95% CI: 0.52-0.82, p=0.0002). TIMI major bleeding classification was lower in males compared to females, with an OR of 0.61 (95% CI: 0.42-0.88, p = 0.009). This indicates higher rates of major bleeding in females compared to males; and Similar findings were also observed with TIMI minor (OR 0.65, 95% CI: 0.46-0.92, p=0.01). Conclusions: These findings highlight the disparities in clinical outcomes of dual antiplatelet therapy following PCI. Females had higher rates of significant bleeding events and all-cause mortality compared to males. This underscores the necessity of investigating the underlying mechanisms driving this gap, emphasizing the need for further research in order to understand and address these differences.
Abstract 4141755: New internet-based warfarin anticoagulation management approach after mechanical heart valve replacement: prospective, multicenter, randomized controlled trial
Authors: Zhihui Zhu, Meng He, Haibo Zhang, Yongqiang Lai
Journal: Circulation (2024)

Background: Mechanical heart valve replacement (MHVR) is an effective method for the treatment of severe heart valve disease. However, it subjects patients to lifelong warfarin therapy after MHVR, with the attendant risk of bleeding and thrombosis. Whether internet-based warfarin management reduces complications and improves patient quality of life remains unknown. Objective: This study aimed to compare the effects of internet-based warfarin management and the conventional approach in patients who received MHVR in order to provide evidence regarding alternative strategies for long-term anticoagulation. Methods: This was a prospective, multicenter, randomized, open-label, controlled clinical trial with a 1-year follow-up. Patients who needed long-term warfarin anticoagulation after MHVR were enrolled and then randomly divided into conventional and internet-based management groups. The percentage of time in the therapeutic range (TTR) was used as the primary outcome while bleeding, thrombosis, and other events were the secondary outcomes. Results: A total of 721 patients were enrolled. The baseline characteristics did not reach statistical differences between the two groups, suggesting the random assignment was successful. As a result, the internet-based group showed a significantly higher TTR (mean 0.53, SD 0.24 vs. mean 0.46, SD 0.21; P &lt; .001) and fraction of time in the therapeutic range (mean 0.48, SD 0.22 vs. mean 0.42, SD 0.19; P &lt; .001) than did those in the conventional group. Furthermore, as expected, the anticoagulation complications, including bleeding and embolic events, had a lower frequency in the internet-based group than in the conventional group (6.94% vs. 12.74%; P = .01). Logistic regression showed that internet-based management increased the TTR by 7% (odds ratio [OR] 1.07, 95% CI 1.05-1.09; P &lt; .001) and reduced the bleeding and embolic risk by 6% (OR 0.94, 95% CI 0.92-0.96; P = .01). Moreover, low TTR was found to be a risk factor for bleeding and embolic events (OR 0.87, 95% CI 0.83-0.91; P = .005). Conclusions: Internet-based warfarin management is superior to the conventional method, as it can reduce anticoagulation complications in patients who receive long-term warfarin anticoagulation after MHVR.
Abstract 4141717: Feasibility of point-of-wear patient satisfaction surveys to validate patient-centered product enhancements: results from over 300,000 patients for long-term ambulatory cardiac monitoring
Authors: Anthony Battisti, Ross Santee, Alice Fan, Relana Pinkerton, Hardwin Mead, Mintu Turakhia
Journal: Circulation (2024)

Introduction: Although 14-day patch-based long-term continuous ambulatory ECG monitoring (LTCM) has shown greater diagnostic yield and lower retest rates compared to other rhythm monitoring modalities, wear can still be limited by factors related to patient comfort and acceptance. Rather than data from small, non-generalizable focus groups, patient survey data at point of care offered to all patients may be valuable in collecting quality improvement data on product experience and satisfaction. We assessed the feasibility of this approach to compare patient satisfaction associated with the prior generation LTCM to that of a new generation, FDA-cleared LTCM product designed with patient-centered features, including a more breathable adhesive, waterproof housing, thinner profile, and lighter weight. Methods: Starting in March 2018, we implemented a survey provided to all patients prescribed Zio® XT LTCM (iRhythm Technologies, San Francisco, CA) to complete and return at end of wear. The survey was completed via paper card or digitally via a web address printed on the card. The survey included questions regarding ease of use, comfort, ability for normal activity, and willingness to wear the device again. Scores of 4 or 5 (i.e., Agree or Strongly Agree) on a Likert scale were considered affirmative responses. Beginning in April 2022, the new Zio® Monitor device was launched for use and the same survey method was used. We compared survey responses for Monitor and XT between Jan 1 and Dec 31, 2023. Results: Among 334,054 respondents, the new LTCM was associated with a greater proportion of affirmative responses across all survey categories (Table 1), with the largest gains in comfort of wear (79.1% vs. 64.7%; p&lt;0.001), ability for normal activity (90.7% vs. 83.3%; p&lt;0.001) and willingness to wear again (89.9% vs. 82.6%; p&lt;0.001). Conclusion: Patient survey data for post-market quality assessment is feasible for digital health technologies, in this case leading to over 300,000 total respondents in one year. Measures of patient satisfaction were higher with the new device, which may be due to patient-centered product enhancements.z
Abstract 4141732: Small Left Ventricular Chamber Size and Mortality in a General Population
Authors: David Leibowitz, Donna Zwas, Offer Amir, Israel Gotsman
Journal: Circulation (2024)

Background: Enlargement of the left ventricle (LV) is well recognized as an important marker of adverse cardiac remodeling and poor prognosis in the setting of known cardiovascular disease as well as in general populations. Previous studies demonstrated increased cardiovascular risk in small subsets of patients with small LV chamber size, however, the prognostic implications of small chamber size in a general population remains unclear. The objective of this study was to examine the prognosis of a small LV chamber in a large cohort of patients undergoing echocardiography. Methods: All consecutive subjects that underwent echocardiography examinations recorded in the echocardiography database of a university-affiliated laboratory from 2011 to 2023 were retrieved for analysis. Small chamber size was defined as end-diastolic diameter less than 42 mm for men and 37.8 mm for women as per ASE guidelines. The primary endpoint for the study was all-cause mortality. Results: 46,529 subjects (mean age 60 ± 19 yrs, 56% males) were included in the study of whom 3,787 had small LV chamber size. Clinical variables associated with small chamber included increasing age and lower BSA. Echocardiographic variables included higher relative wall thickness, and E:e' . On multivariate analysis, the presence of a small LV was significantly associated with mortality (HR 1.43 with 95% CI 1.33-1.54; p &lt;0.001). This finding was significant in both older (over 65) (HR 1.30 95% CI 1.19-1.41; p &lt;0.001) and younger (HR 2.09 95% CI 1.81-2.41; p &lt;0.001) subjects and in both males and females. Conclusions: In this retrospective large cohort study, small LV chamber size was significantly associated with mortality in a broad range of patients. Further study is necessary to elucidate the mechanisms for this finding.
Abstract 4141742: HFpEF with resting LVEF &gt;60% exhibit a distinct exercise response and circulating proteome to HFpEF with LVEF &lt;60%
Authors: Roshan Xavier, Sher May Ng, Jiliu Pan, Jack Miller, Ferenc Mozes, Ladislav Valkovic, Jennifer Rayner, Matthew Fronheiser, Marzia Rigolli, Stefan Neubauer, Oliver Rider, Andrew Lewis
Journal: Circulation (2024)

Introduction: Heterogeneity in heart failure with preserved ejection fraction (HFpEF) is an important challenge for the development of new medicines for this disease. Clinical trials of SGLT-2 inhibitors and renin-angiotensin inhibition have demonstrated reduced efficacy in patients with higher LVEF. With the advent of myosin modulation, there is renewed focus on those with LVEF &gt;60% as a group that could benefit. Hypothesis: Patients with HFpEF and LVEF &gt;60% will have impaired cardiac response to exercise stress and reduced functional capacity compared to HFpEF with LVEF &lt;60% with a distinct circulating proteome. Methods: Patients with HFpEF (n=64, mean age 76.6± 5.5) and age-matched controls (n=16, mean age 71.9 ± 6.2) were prospectively enrolled. Assessment of cardiac volumes, function and stress response was performed using real-time cardiovascular magnetic resonance imaging at rest and sub-maximal exercise (35W for 6 minutes). Plasma samples were acquired immediately after exercise for aptamer-based proteomics to detect 7000 circulating proteins. Pathway enrichment analysis of the proteome was performed to compare both HFpEF groups to controls. Results: HFpEF patients with high LVEF (&gt; 60%, n=46) had smaller left ventricular volumes (LVEDVi 64.8 ± 14.7 vs 93.6 ± 17.1 ml/m 2 , p&lt;0.001) compared to HFpEF patients with lower LVEF (50-60%, n=18). During exercise, HFpEF patients with high LVEF had attenuated systolic augmentation (LVEF +3.1 ± 4.9 vs +5.5 ± 3.6 %, p=0.03), lower cardiac index (4.5 ± 1.1 vs 5.2 ± 1.3 L/min/m 2 , p=0.06) and lower 6-minute walk distance (348 ± 95 vs 401 ± 76m, p=0.03). When compared to controls, HFpEF patients with high LVEF had a distinct plasma proteomic signature, characterized by altered lipid metabolism pathways whereas those with lower LVEF had perturbed extracellular matrix organisation and inflammatory pathways. Conclusions: Patients with HFpEF and LVEF &gt;60% have greater functional impairment, smaller LV cavities, blunted systolic augmentation to exercise and a circulating proteome characterised by altered lipid metabolism pathways. These findings support stratified approaches to this group in future clinical trials and identify potential novel biomarkers to assess treatment response.
Abstract 4141743: Lipoprotein(a) and Outcomes After Coronary Angiography
Authors: Kelvin Supriami, Christian Andersen, Roberto Tello Ayala, So Mi Jemma Cho, Eugene Pomerantsev, Patrick Ellinor, Michael Honigberg, Akl Fahed
Journal: Circulation (2024)

Background: Lipoprotein(a) [Lp(a)] is a potent risk factor for coronary artery disease (CAD) with novel Lp(a)-lowering therapeutics under investigation. Data regarding implications of elevated Lp(a) among patients undergoing coronary angiography are limited. We aimed to assess (i) the association between Lp(a) levels and angiographic characteristics of CAD and (ii) whether Lp(a) levels predict adverse angiographic and clinical outcomes after index coronary angiogram. Methods: Patients who underwent coronary angiography and Lp(a) measurement between 2000-2023 were classified into four Lp(a) risk groups: normal (&lt;75 nmol/L), intermediate (75-124 nmol/L), high (125-174 nmol/L), and very high (≥175 nmol/L). Angiographic characteristics (severity, burden, Gensini score—a continuous measure of angiographic CAD burden) and future outcomes starting 3 months after index angiogram (repeat angiogram, revascularization, in-stent restenosis [ISR], heart failure [HF], and all-cause mortality) were analyzed by Lp(a) risk category using Cox proportional hazard models adjusted for age, sex, and race. Results: Among 5,118 patients (26.5% female; median [IQR] age 64 [55-74]; 84.9% White), 3,138 (61.3%) had normal Lp(a) levels, 543 (10.6%) intermediate, 464 (9.1%) high, and 973 (19%) very high. Compared to normal Lp(a) levels, very high Lp(a) was associated with obstructive CAD (adjusted odds ratio [AOR], 1.50; 95%CI, 1.16-1.94), multi-vessel disease (AOR,1.79; 95%CI, 1.39-2.30), left-main disease (AOR, 1.80; 95%CI, 1.33-2.45), and a 13.9-point increase in the Gensini score (P&lt;.001). Over a mean follow-up of 11.01±7.58 years, patients with very high Lp(a) were significantly more likely to undergo a repeat angiogram (adjusted hazard ratio [AHR], 1.22; 95%CI, 1.09-1.36), revascularization (AHR, 1.40; 95%CI, 1.19-1.64), and ISR (AHR, 1.34; 95%CI, 1.10-1.63). However, no increased risk of HF was observed ( P &gt;.05). The risk of mortality was 17% higher in the very high Lp(a) group (95%CI, 1.04-1.32). These trends persisted even after adjusting for baseline CAD burden ( Figure ). Conclusion: Very high Lp(a) levels are associated with increased burden and severity of CAD and are strongly predictive of future angiographic and clinical outcomes.
Abstract 4141726: Ceramides produced by gut bacteria <i>Bacteroides thetaiotaomicron</i> causally induce aortic perivascular adipose tissue-endothelial cell senescence in aged host
Authors: Khatereh Shabanian, Benoit Pugin, Florentin Constancias, Taraneh Shabanian, Karsai Gergely, Cristina Menni, Thorsten Hornemann, Matthias Hermann, Francesco Paneni, FRANK RUSCHITZKA, Soheil Saeedi
Journal: Circulation (2024)

Introduction: Specific ceramides play a crucial role in cellular senescence by upregulating the SASP in the vasculature, leading to atherosclerosis in the aging population. Gut microbiota is emerging as a regulator of circulating ceramides in the host. However, it remains unknown what/how gut bacteria causally regulate ceramide-induced perivascular adipose tissue (PVAT) and endothelial cell (EC) senescence in aging. Methods: To address the knowledge gap in gut-derived ceramides and their regulation of (peri)vascular aging, we performed high-throughput multi-omics (fecal shotgun metagenomics and plasma LC-MS/MS lipidomics) coupled with bacterial colonization, senescence, and cell-cell interaction studies. Results: Our metagenomic and plasma lipidomic studies on human (TwinsUK Aging Cohort, n=900; Aging Heart Zurich Cohort, n&gt;800) and mouse (&gt;24 vs. 3 months, n=6) aging cohorts pinpointed a higher abundance of Bacteroides thetaiotaomicron (B. theta) harboring the serine palmitoyltransferase ( SPT ) gene, synthesizing deleterious ceramides C18:1/16:0 and C18:1/18:0 in old hosts. Importantly, plasma levels of the ceramides were positively associated with major adverse cardiovascular events (MACE) in atherosclerotic CVD patients within the Aging Heart Zurich Cohort (n=105). In vivo colonization of young mice with B. theta (4-weeks) confirmed a marked increase in circulating Cer 18:1/16:0 and 18:1/18:0, accompanied by higher signals of the SASP component IL6 and the proliferative arrest marker p16 INK4a in aortic PVAT and ECs. These mice also exhibited reduced vasorelaxation responses and angiogenic incompetence. As a proof of concept, our PVAT-EC co-culture studies demonstrated that addition of the ceramides induces senescence and dysfunction in PVAT by upregulating Notch1 signaling. This upregulation increases IL1β and its downstream IL6, leading to the downregulation of adipocyte function markers UCP1 and adiponectin. The released IL6 also induced a senescence phenotype in ECs, evidenced by increased SA-β-gal activity, DNA damage response (↑ γ-H2A.X), telomere attrition (↓ hTERT), and proliferative arrest (↑ p16 INK4a &amp;p19 INK4d ). Conclusion: This research identifies B. theta as a causal contributor to deleterious ceramides in the host circulation, leading to (peri)vascular senescence and dysfunction in aging. Targeting B. theta offers a novel microbiome-based approach to decelerate (peri)vascular senescence and extend healthspan, with potential clinical applications.
Abstract 4141710: Artificial Intelligence Guided Stress Perfusion Cardiac Magnetic Resonance Versus Standard-Of-Care in Stable Chest Pain Syndromes
Authors: Isabela Reis Marques, Marianna Daibes, Benedikt Bernhard, Michael Jerosch-Herold, Bobak Heydari, Okai Addy, Lori Powell, Juan Santos, Bob Hu, Raymond Kwong
Journal: Circulation (2024)

Background: Stress perfusion CMR has excellent diagnostic and prognostic values in assessing chest pain syndromes. AI-guided methods may overcome complex scanning and increase clinical adaptation of stress CMR. Aim: To assess the benefits of AI-guided stress perfusion CMR. Methods: Consecutive patients with stable chest pain underwent stress CMR using either a standard scanning method (SOC) or an AI-assist (AIA) machine learning protocol to automate scan planning, plane prescription, sequence tuning, and image reconstruction. Scan duration, the ratio of scan preparation time over the entire scan duration, and scan quality using a 5-point scale were compared between AIA and SOC. Cox regression models were constructed to associate evidence of ischemia on stress CMR, by either scanning method, with composite endpoints including cardiovascular death, non-fatal MI, unstable angina hospitalization, and late CABG. A second composite endpoint included the performance of additional cardiac imaging tests (stress imaging and CCTA) and invasive coronary procedures after CMR. Results: Among 594 patients (62.8 ± 14 years), 29% underwent stress CMR with AIA. 26% had stress-perfusion ischemia, and 39% had LGE present. AIA stress CMR had lower scan duration (median 44.0 [IQR 40-47] vs. 52.5 min [IQR 46-60]; p&lt;0.001), lower preparation time ratio (median 0.11 [IQR 0.09-0.15] vs. 0.21 [IQR 0.16-0.31], p&lt;0.001) and a higher mean image quality score (mean 4.2±0.7 vs. 3.9±0.6; p&lt;0.001) compared to SOC. There was a trend to a lower risk of experiencing the clinical composite endpoint and a lower need to undergo subsequent noninvasive testing among the AIA group (log-rank p=0.33 and p=0.08). Among the 152 patients with ischemia present, the incidence of invasive referral and performance of coronary revascularization within 90 days were not different. Conclusions: In this non-randomized observational cohort, AIA significantly improved stress CMR scan duration, preparation time ratio, and image quality compared to SOC.
Abstract 4141751: Exercise-Induced Improvements in Capillary Density are Influenced by Sex, Hormone Replacement Therapy, and Exercise Intensity
Authors: Anna-Maria Dagher, Katherine Collins, Leanna Ross, Brian Duscha, Joseph Houmard, Brian Annex, William Kraus
Journal: Circulation (2024)

Background: While cardiometabolic disease (CMD) is the top cause of death for US women, age at onset is 10-20 years after that of men largely due to menopausal estrogen loss. Along with premenopausal estrogen, exercise decreases CMD risk in part by increasing capillary density (CD). To better understand CMD risk in postmenopausal women, we investigated the impact of sex, hormone replacement therapy (HRT), and exercise amount/intensity on CD. We hypothesized that compared to women not using HRT and independent of exercise amount/intensity, women using HRT and men would display greater exercise improvements in CD and lesser declines during a detraining period. Methods: Previously sedentary adults with overweight/obesity (n=228) were randomized to an inactive control or one of three 6-mo exercise groups: 1) low-amount/moderate-intensity (LAMI); 2) low-amount/vigorous-intensity (LAVI); or 3) high-amount/vigorous-intensity (HAVI). Biopsy-derived skeletal muscle CD was measured at baseline, 24-h-, 4-days-, and 14-days post-intervention (detraining period). Change scores were calculated by subtracting baseline from post-intervention CDs and analyzed using one-way ANOVA and post-hoc by two-tailed two-sample t-tests. The effects of sex, HRT, and exercise group on CD over time were assessed by linear mixed models. Results: Exercise significantly increased CD in all groups except LAMI women not using HRT and LAVI men. In vigorous-intensity groups, men increased CD through detraining while women rapidly returned to baseline. With LAMI exercise, CD in women not using HRT and men returned to baseline with detraining. Women using HRT with LAMI, but not vigorous-intensity exercise, sustained CD improvements through detraining. Conclusions: Sex, HRT, and exercise intensity impacted CD responses to exercise and detraining. Men and women performing vigorous-intensity exercise display disparate detraining responses, indicating women require continued training to maintain exercise-induced CD improvements. HRT sustained CD improvements through detraining in women performing LAMI but not vigorous-intensity exercise. These findings influence recommended exercise frequency and intensity by sex and HRT use to decrease postmenopausal CMD risk.