tbuckley/cabot-search huggingface dataset:
Abstract 4138813: The Use of Direct Oral Anticoagulants for Valvular Atrial Fibrillation in Central Australia
Authors: Sonia Sawant, Gabrielle Freedman, Sally Terrett, Ana Garcia, Chinmay Khandkar, Anosh Sivashanmugarajah, Angus Baumann
Journal: Circulation (2024)

Background: In developed countries, valvular atrial fibrillation (vAF) in the setting of rheumatic heart disease (RHD) disproportionately impacts minority groups. In Australia, Indigenous Australians account for 92% of cases despite only representing 3.8% of the population. Studies to date, such as the INVICTUS trial, support the use of Vitamin K antagonists (VKAs) over direct oral anticoagulants (DOACs) in vAF. However, this assumes consistent adherence and regular clinic follow up. Reduced access to monitoring and dispensing clinics in Central Australia remains a challenge in the provision of VKAs and the use of DOACs may address this. Hypothesis: DOACs may be comparably effective with VKAs in preventing major adverse cardiac and cerebrovascular events (MACCE) in a real-world vAF population. Aim: To conduct a real-world retrospective observational study examining rates of MACCE for patients on VKAs or DOACs for vAF in Central Australia over a five-year period. Methods: The Northern Territory RHD Register was accessed to identify patients with RHD and vAF in January 2019. Demographic and five-year outcome data (until January 2024) were collected. The primary outcome was MACCE, a composite of ischaemic stroke, systemic embolism, non-fatal myocardial infarction, cardiovascular death and all-cause mortality. The primary safety endpoint was major bleeding. Statistical analyses were conducted as both intention-to-treat (ITT) based on initial anticoagulation and as-treated (AT) based on anticoagulation prior to MACCE or trial endpoint, each excluding patients without anticoagulation. Results: 61 patients were included. The mean age was 61.9 ± 13.9 years and 68.9% were female. At baseline, 65.6% received VKA, 14.8% DOAC and 19.7% were not anticoagulated. 30.6% of patients crossed over from the ITT analysis, with a non-significant trend favouring switch to DOAC (11 vs 0, p=0.09). In the ITT analysis (n=49), there was no significant difference in MACCE (25.0% vs 22.2%, p=0.86) or major bleeding (20.0% vs 11.1%, p=0.53) between VKA and DOAC groups. In the AT analysis (n=51), there was no significant difference in MACCE (27.3% vs 16.7%, p=0.39) or major bleeding (18.2% vs 22.2%, p=0.73) between VKA and DOAC groups. Conclusion: Over a five-year period, there was a trend towards use of DOACs over VKAs in vAF. This study demonstrates that DOACs may be as effective as VKAs for reducing MACCE in a real-world vAF population however further investigation is required.
Abstract 4138781: Neuro-specific biomarkers for risk assessment of ischemic stroke and death in patients with atrial fibrillation not receiving oral anticoagulation
Authors: Julia Aulin, Karl Sjolin, Johan Lindbäck, Alexander Benz, John Eikelboom, Jonas Oldgren, Lars Wallentin, Joachim Burman
Journal: Circulation (2024)

Background: Biomarkers measured in plasma reflecting cardiorenal dysfunction and inflammation are associated with clinical outcomes in atrial fibrillation (AF). We recently showed an association between the plasma level of the neuronal biomarker neurofilament light chain (NFL) and subsequent stroke and death in patients with AF not receiving oral anticoagulation (OAC). Purpose: We aimed to compare NFL with other circulating neuro-specific biomarkers, specifically glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), concerning associations with the risk of stroke and other outcomes in patients with AF. Methods: Concentrations of NFL, GFAP, tau, and UCHL1 were determined with Single Molecule Array (Simoa®) in plasma samples obtained at baseline from 967 patients with AF randomized to aspirin in the ACTIVE A trial. Median follow-up was 3.6 years. Associations between baseline biomarker concentrations, clinical variables (age, sex, body mass index, smoking, alcohol consumption, type of AF, cardiac rhythm at baseline, heart failure, hypertension, diabetes, prior stroke/transient ischemic attack, peripheral arterial disease, and myocardial infarction), and outcomes (ischemic stroke, cardiovascular and all-cause death) were analysed with Cox regression, adjusting for clinical variables and other biomarkers. Results: Increasing age and female sex were associated with elevated levels of all four biomarkers. Plasma levels of NFL were positively correlated with those of GFAP (r=0.67, p&lt;0.001), tau (r=0.12, p&lt;0.001), and UCHL1 (r=0.37, p&lt;0.001). NFL was independently associated with subsequent ischemic stroke (HR 1.27, 95% CI 1.03–1.56 for a doubling of NFL), cardiovascular death (HR 1.37, 95% CI 1.13–1.64 for a doubling of NFL), and all-cause death (HR 1.46, 95% CI 1.25–1.70 for a doubling of NFL) after adjustment for clinical factors and other biomarkers. In unadjusted analyses, GFAP was associated with ischemic stroke and death; tau and UCHL1 with death only, however, these associations were not significant after adjusting for clinical variables (Table). Conclusions: In patients with AF not receiving OAC, NFL was independently associated with ischemic stroke and death. Further investigation of NFL and its association with clinical outcomes in patients with cardiovascular disease is therefore warranted.
Abstract 4138633: Infusion of human apolipoprotein A-I (CSL112) promotes several aspects of reverse cholesterol transport
Authors: Rommel Mathias, Elena Velkoska, Svetlana Diditchenko, Brandon Greene, Xiahui Tan, Alexey Navdaev, Heidi Collins, Steven Adelman, Kyal Young, Andreas Gille, Danielle Duffy, C. Michael Gibson, Matthias Pelzing, Bronwyn Kingwell
Journal: Circulation (2024)

Background: High-density lipoprotein (HDL)-cholesterol is inversely correlated with cardiovascular risk, but increasing its circulating concentration is insufficient to prevent adverse cardiovascular outcomes. Instead, the emerging paradigm is on increasing the function of HDL and its major protein constituent apolipoprotein A-I (apoA-I), to increase reverse cholesterol transport. Objective: To investigate the effect of apoA-I [human] (CSL112) infusion on HDL protein composition, and provide further insights into the mechanism of action of CSL112 administered post-acute myocardial infarction (AMI). Methods: A mass spectrometry (MS)-based proteomic approach was used to evaluate changes in HDL protein composition in patients (n=50) from the AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) study who received either placebo or CSL112 post AMI. HDL was immuno-isolated from patient plasma using anti-apoA-I antibodies. Cholesterol esterification rate (CER) was measured to determine lecithin-cholesterol acyl transferase (LCAT) activity. Cholesterol efflux capacity (CEC) and hepatocyte uptake were assessed using patient serum in ex vivo cell-based assays. Results: CSL112 induced extensive rearrangement of HDL proteins at 4 hours post-infusion. Levels of apolipoproteins A2, B, C, and E as well as the acute phase proteins serum amyloid A1 and A4 were significantly reduced. By contrast, apoA-I, apoM, and LCAT significantly increased. Elevated apoA-I and LCAT levels on HDL were associated with an increase in CEC, plasma HDL-C levels, and CER in CSL112-treated patients. Furthermore, enhanced CEC strongly correlated with cholesterol uptake by hepatic cells (r=0.95 p&lt;0.001). Conclusion: CSL112 altered HDL composition and increased HDL functionality by promoting multiple steps of the reverse cholesterol transport pathway.
Abstract 4138715: Disparities in Aortic Dissection and Aortic Aneurysm-Related Mortality in The United States From 1999-2020
Authors: Maryam Shahzad, Mariyah Zainab Irfan, FNU Danisha, Vikash Jaiswal, Jishanth Mattumpuram
Journal: Circulation (2024)

Background: Aortic dissection (AD) and aneurysm (AA) have a low incidence but are severe health risks associated with high mortality rates, and based on location, can have a mortality rate of over 80%. We aim to highlight disparities in mortality based on gender, race, age and demographic background. Methods: This retrospective study analyzed death certificate data for AD and AA (ICD-10 code I71) from 1999 to 2020 using the CDC WONDER database. Age-adjusted mortality rates (AAMR) per 100,000 were assessed for adults aged 25 and older by gender, race, year, state, and place of death, while crude mortality rates (CMR) per 100,000 were used for age groups. Joinpoint regression calculated the annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals. Results: From 1999 to 2020, AD and AA resulted in 400,748 deaths in the US. During this period, AAMR for men (12.19) was approximately double that for women (5.77). Overall, the AAMR decreased from 12.40 to 6.71 (AAPC: -2.93; 95% CI: -3.06 to -2.79; p-value&lt;0.000001). NH whites had the highest AAMR at 8.93, while Hispanic and Latino populations had the lowest at 4.20. Approximately 52.3% of the deaths occurred in inpatient medical facilities, whereas 18.4% occurred at home. Vermont, West Virginia, and Wyoming had the highest AAMRs, at 11.60, 11.47, and 11.30, respectively. Among racial groups, both males and females experienced a decrease in AAMR except for NH black men. For this group, there was an increase in AAMR from 9.42 in 2012 to 10.43 in 2020 (APC:1.03; 95% CI: 0.15 to 2.22; p-value:0.028). The CMR for young adults rose significantly from 0.62 in 2014 to 0.73 in 2020 (APC:2.55; 95% CI 1.11 to 6.74; p-value:0.02), and for middle-aged adults from 3.09 in 2010 to 3.61 in 2020 (APC: 1.57; 95% CI 1.04 to 2.25; p-value&lt;0.000001). Conversely, a steep decline in CMR was observed for older adults from 27.93 in 2014 to 25.4 in 2020 (APC:-1.34; 95% CI -1.9 to -0.69; p-value:0.0004). Conclusion: Although AD and AA mortality rates have declined over time, significant disparities persist for NH Black men and young/middle-aged adults. This highlights the need for early screening programs and equitable healthcare provision for all populations.
Abstract 4138721: Outcomes of Coronary Revascularization in Patients with Contemporaneous Abdominal Organ Transplant
Authors: Siavash Zamirpour, Justin Zhang, Elaine Tseng, Krishan Soni, Marko Boskovski
Journal: Circulation (2024)

Background: Clinical evaluation surrounding liver and kidney transplantation may reveal obstructive coronary artery disease (CAD). However, little is known about outcomes after revascularization in this population. Our aim was to examine coronary artery bypass grafting (CABG) and percutaneous intervention (PCI) in peri-transplant patients compared to the general CABG/PCI populations. Methods: We conducted a matched retrospective cohort study between 2014-2022 at a single academic center. Matching was done by optimal full matching of a logistic regression-based propensity score adjusting for age, chronic kidney disease, diabetes, tobacco use, chronic lung disease, hypertension, prior myocardial infarction, and valvular disease. Covariate balance was assessed as standardized mean difference &lt;0.2. The primary outcome was a composite of in-hospital death, stroke, and myocardial infarction, and a key secondary outcome was incident arrhythmia. Results: The study population comprised 2655 patients: 24 CABG/transplant (median age, 64 [IQR, 59-66]; 4 female [17%]), 1037 CABG/non-transplant (age, 66 [59-73]; 190 female [18%]), 27 PCI/transplant (age, 62 [IQR, 55-67]; 6 female [22%]), and 1567 PCI/non-transplant (age, 70 [IQR, 60-78]; 399 female [25%]). CABG/PCI preceded transplant by a median 321/324 days, respectively, and followed transplant by a median 461/36 days, respectively. For the primary outcome in CABG patients, there were no events in the transplant group and an estimated potential outcome in 6.5% of the matched non-transplant group (marginal RR, &lt;0.001; p&lt;0.001). For the primary outcome in PCI patients, there were no events in the transplant group and an estimated potential outcome in 2.4% of the matched non-transplant group (marginal RR, &lt;0.001; p&lt;0.001). For incident arrhythmia in CABG patients, the estimated potential outcome was 12% and 17.5% in the transplant and matched non-transplant groups, respectively (marginal RR, 0.98; 95% CI, 0.37-2.6; p=0.97). For incident arrhythmia in PCI patients, the estimated potential outcome was &lt;0.001% and 3.6% in the transplant and matched non-transplant groups, respectively (marginal RR, 0.89; 95% CI, 0.12-6.5; p=0.91). Conclusions: Patients with contemporaneous abdominal organ transplant undergoing coronary revascularization suffered no in-hospital mortality, stroke, or myocardial infarction, and were not at greater risk of incident arrhythmia than similar non-transplant patients.
Abstract 4138714: Implementation of the KDIGO Guidelines to Prevent Cardiac Surgery Associated Acute Kidney Injury in Patients with Heart Failure With Preserved Ejection Fraction Undergoing Coronary Artery Bypass Grafting
Authors: Heng Zhang, Jiawei Han, Juntong Zeng, Xiaoting Su, Hongyan Zhou, Sheng Liu, Zhe Zheng
Journal: Circulation (2024)

Backgrounds: The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommended the initiation of multiple supportive measures in patients at high risk for cardiac surgery associated acute kidney injury (CSA-AKI). Heart failure with preserved ejection fraction (HFpEF) was known as a critical risk factor for CSA-AKI. Purpose: Our study was designed to assess the effectiveness of KDIGO guidelines and the risk of CSA-AKI following coronary artery bypass grafting (CABG) among patients with HFpEF. Methods: This retrospective cohort study included 7420 patients undergoing CABG from 2019 to 2022, including 1960 patients with pre-operative HFpEF and 5460 patients without pre-operative HF as comparison. Implementation of the KDIGO guidelines consists of 6 measures in the first 72 hours after surgery, including avoidance of nephrotoxic agents, discontinuation of ACEi and ARB, implementation of advanced hemodynamic monitoring, avoidance of hyperglycemia, optimization of hemodynamics, and intensified monitoring of renal function. The primary outcome was in-hospital postoperative AKI according to the KDIGO criteria. Results: Among the included patients with HFpEF, 125 (6.4%) patients were classified as fully implementing the KDIGO guidelines. For the primary outcome, implementation of guidelines was associated with a significantly decreased risk of CSA-AKI (46.4% vs. 62.0%; OR, 0.591 [95% CI, 0.407-0.857]; p = 0.006). Meanwhile, implementation of guidelines had a greater preventive effect on CSA-AKI for HFpEF patients compared with non-HF patients (OR, 0.921 [95% CI, 0.759-1.118]; p = 0.405). Noticeably, we found that avoidance of hyperglycemia (OR, 0.737 [95% CI, 0.591-0.920]; p = 0.007) and optimization of hemodynamics (OR, 0.638 [95% CI, 0.508-0.802]; p &lt; 0.001) were associated with lower incidence of CSA-AKI. Conclusions: Despite a lack of adherence to the KDIGO guidelines in patients undergoing CABG, implementation of the guidelines was found to be associated with a significantly lower risk of CSA-AKI for patients with HFpEF. Among the measures in the guidelines, avoidance of hyperglycemia and optimization of hemodynamics had stronger preventive effects for CSA-AKI.
Abstract 4138738: Clinical Evidence of Immune Response to Transplanted Allogeneic iPS Cell-Derived Cardiomyocytes
Authors: Takuji Kawamura, Emiko ito, Maki Takeda, Daisuke Yoshioka, Ai Kawamura, Yusuke Misumi, Shunsuke Saito, Takashi Yamauchi, Shigeru Miyagawa
Journal: Circulation (2024)

Background&amp;Purpose: The clinical application of cell transplantation therapy utilizing induced pluripotent stem cells (iPS cells) for heart failure is progressing, with the primary strategy being the use of pre-prepared allogeneic iPS cells. The immune response to these transplanted cells is crucial and may affect therapeutic efficacy, necessitating the use of immunosuppressive drugs. However, detailed clinical reports on immune responses are sparse. This study aims to analyze the immune response to transplanted cells in clinical iPS cell-derived cardiomyocyte (iPSC-CM) transplants and examine the correlation between immune response and therapeutic efficacy. Methods: In the "Phase 1 multicenter clinical trial of transplantation of iPSC-CMs for ischemic cardiomyopathy" (https://jrct.niph.go.jp/en-latest-detail/jRCT2053190081), conducted as the First-in-Human trial, the immune response to transplanted cells was analyzed in four cases at our hospital. Comprehensive analysis of anti-human leukocyte antigen (HLA) antibodies in serum and single-cell RNA sequencing in peripheral blood mononuclear cells was performed to investigate their relationship with therapeutic effects on cardiac function. Results: Patients received immunosuppressive drugs (tacrolimus, mycophenolate mofetil, and steroids) for 3 months post-transplantation, followed by a 1-year follow-up. In all cases, an increase in transplant cell HLA-specific antibodies was observed after discontinuing immunosuppressive drugs (Figure 1 and 2). Single-cell analysis revealed a decrease in immunocompetent cells in peripheral blood during immunosuppressive therapy. Cardiac function analysis showed improvements in all cases except Case 2 (Figure 3), where pre-existing anti-HLA-DQ antibodies were present before transplantation. Conclusions: No immune response to the transplanted cells was observed during immunosuppressive therapy. In a case with limited therapeutic response, pre-existing antibodies to transplanted cells were detected, potentially impacting the therapeutic outcome.
Abstract 4138698: Association of ALDH2*2 Variant with Increased HDL-Cholesterol Levels in East Asian Populations
Authors: Ruina Zhang, Subhanik Purkayastha, Kabir Malkani, Sean Heffron
Journal: Circulation (2024)

Background: Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is responsible for acetaldehyde metabolism with alcohol consumption. ALDH2 deficiency is a common enzymopathy – afflicting ~540 million East Asians. The ALDH2*2 variant, a missense mutation, significantly decreases enzyme activity. Recent studies suggest a potential link between ALDH2 deficiency and increased cardiovascular disease (CVD) risk. High-Density Lipoprotein cholesterol (HDL-C) is inversely associated with CVD and is known to increase with alcohol consumption. However, the impact of ALDH2*2 on HDL-C levels in East Asians remain unclear. Methods: Using the NIH All of Us cohort, we assessed HDL-C levels and reported alcohol consumption habits (never, &lt; once/week, &gt; once/week) at enrollment, as well as ALDH2 variant status among East Asian participants. Differences in HDL-C values were analyzed with Mann-Whitney U-tests. Results: Among 3,289 US Asian adults (age 46.8 ± 16.1 years; 58.8% female), median HDL-C was 54mg/dL [IQR 45, 67]. Of these, 2809 (85.4%) had wildtype ALDH2, and 480 (14.6%) had ALDH2*2 . Individuals with ALDH2*2 reported lower alcohol consumption (Figure A) but exhibited higher HDL-C levels (p=0.0002). The association was similar regardless of sex (Figure B). Conclusion: The ALDH2*2 variant is associated with higher HDL-C levels, despite lower alcohol consumption, indicating a possible independent influence on HDL-C levels. In the context of previous studies linking ALDH2 deficiency to adverse CVD outcomes, this suggests that ALDH2 may have a role independent of HDL-C levels, or it could affect HDL function rather than the HDL-C level itself.
Abstract 4138757: Lipid-Lowering Therapy Intensification and Low-Density Lipoprotein Cholesterol Testing Following a Major Cardiovascular Event or Procedure in Adult Patients in the United States
Authors: Ran Jin, Thiago Oliveira, Jenna Jones, Jifeng Ma, Maria Kouznetsova, Rajkumar Sugumaran
Journal: Circulation (2024)

Background: Optimizing lipid-lowering therapy (LLT) use is foundational to reduce atherosclerotic cardiovascular disease (ASCVD) risk, especially among patients who have already experienced an ASCVD event. This study aimed to evaluate the patterns of LLT intensification and LDL-C testing within 12 months following an ASCVD event in US patients. Methods: Adults who experienced an ASCVD event (acute coronary syndrome, coronary revascularization, stable angina, ischemic stroke, transient ischemic attack, or peripheral arterial disease) between January 1, 2016 and December 31, 2022 in the IQVIA Longitudinal Access and Adjudication Data were included. The first instance of LLT intensification after the event was defined as an increase from a low-moderate to high intensity statin, or the initiation of statins, ezetimibe, PCSK9i, or bempedoic acid in addition to a baseline LLT regimen that did not include these medications. Baseline medication use was defined during 6 months before the ASCVD event. Results: Among 6,028,573 patients who had an eligible ASCVD event (mean age: 63.6 years, 51.5% male), 53.9% were not taking any LLT and 43.2% were taking statins only (low-moderate intensity: 26.7%; high intensity: 16.4%) during baseline. Within 1, 3, and 12 months after the event, 16.3%, 21.3%, and 30.0% of patients intensified LLT, respectively. Among patients who intensified LLT within 12 months (n= 1,820,246), the most commonly observed intensification was from no LLT use at baseline to low-moderate (29.0%) or high-intensity statins (43.5%), followed by intensification from low-moderate to high-intensity statins (20.3%). LDL-C values at baseline were available in a subset of 10.7% of patients, with the median being 95 mg/dL (78.9% ≥70 mg/dL). LDL-C values were observed in 17.7% of patients within 12 months after the ASCVD event, with the median being 84 mg/dL (68.3% ≥70 mg/dL). Conclusions: Within 12 months after an ASCVD event, only about one-third of patients intensified LLT and two-thirds did not achieve guideline-recommended LDL-C levels. The results highlight a missed opportunity to reduce recurrent ASCVD events. Future effort is warranted to address the clinical inertia that may be contributing to this unmet need.