bluuebunny/crossref_metadata_2025 huggingface dataset:
2024 American Heart Association and American Red Cross Guidelines for First Aid
Authors: Hewett Brumberg Elizabeth K. , Douma Matthew J. , Alibertis Kostas , Charlton Nathan P. , Goldman Michael P. , Harper-Kirksey Katrina , Hawkins Seth C. , Hoover Amber V. , Kule Amy , Leichtle Stefan , McClure Sarah Frances , Wang George Sam , Whelchel Mark , White Lynn , Lavonas Eric J. ,   on behalf of the American Heart Association and American Red Cross
Published: November 2024

Codeveloped by the American Heart Association and the American Red Cross, these guidelines represent the first comprehensive update of first aid treatment recommendations since 2010. Incorporating the results of structured evidence reviews from the International Liaison Committee on Resuscitation, these guidelines cover first aid treatment for critical and common medical, traumatic, environmental, and toxicological conditions. This update emphasizes the continuous evolution of evidence evaluation and the necessity of adapting educational strategies to local needs and diverse community demographics. Existing guidelines remain relevant unless specifically updated in this publication. Key topics that are new, are substantially revised, or have significant new literature include opioid overdose, bleeding control, open chest wounds, spinal motion restriction, hypothermia, frostbite, presyncope, anaphylaxis, snakebite, oxygen administration, and the use of pulse oximetry in first aid, with the inclusion of pediatric-specific guidance as warranted.
Abstract 4138062: Pharmacological inhibition of HDAC6 improves post-infarction cardiac function by limiting mitochondrial fission in type 2 diabetic mice
Authors: Baumgardt Shelley , Zhao Ming , Xia Zhengyuan , Fu Xuebin , Sinha Anshuman , Krishnan Swetha , Mehta Vivek , Nguyen My Linh Thi , Dudley Vincent , Waypa Gregory , Camara Amadou , Winlaw David , Schumacker Paul , Thorp Edward , Ge Zhi-Dong
Published: November 2024

Introduction:
Histone deacetylase (HDAC) 6 functions to remove acetyl groups from lysine residues on histone and non-histone proteins. We showed that the augmented activity of HDAC6 in diabetic mice undergoing myocardial ischemia/reperfusion injury (MIRI) was associated with mitochondrial damage. However, it remains unclear how the inhibition of HDAC6 activity affects post-MIRI cardiac remodeling and function in type 2 diabetes.

Hypothesis:
HDAC6 inhibition suppresses adverse cardiac remodeling and improves mitochondrial dynamics and cardiac function after MIRI in type 2 diabetic mice.

Methods:
Type 2 diabetic db/db, db/+, and C57BL/6 mice underwent coronary artery occlusion for 20 min followed by reperfusion. Tubastatin A, a selective inhibitor of HDAC6, was injected intraperitoneally 60 min before coronary artery occlusion and once daily after surgery. Mouse hearts were evaluated with echocardiography 28 days after surgery. Myocardium was imaged using electron microscopy, and the expression of mitochondrial dynamin-related protein 1 (DRP1) and fission 1 was measured by Western blotting analysis. H9c2 cardiomyocytes were subjected to hypoxia for 3 hours followed by normoxia for 24 hours in the presence of 5.5- or 25.0-mM D-dextrose and tubastatin A or vehicle.

Results:
There were no significant differences in the activity of HDAC6, left ventricular diameters and fractional shortening, mitochondrial density volume and surface area, and the ratios of DRP1/GAPDH and fission 1/GAPDH between the db/+ and C57BL/6 groups. Compared to both db/+ and C57BL/6 groups, HDAC6 activity was lower, left ventricular diameters at both end diastole and end systole were longer, fractional shortening and mitochondrial surface area were smaller, and the expression of DRP1 and fission 1 was increased in the db/db group 28 days after MIRI. Interestingly, 10 mg/kg Tubastatin A significantly mitigated these effects of MIRI in db/db mice. Hypoxia/reoxygenation in the presence of 25.0-mM D-dextrose augmented HDAC6 activity and increased the expression of DRP1 and FIS1, which were blocked by Tubastatin A.

Conclusions:
Tubastatin A prevents post-MIRI cardiac remodeling and improves cardiac function by limiting mitochondrial fission in type 2 diabetic mice.
Abstract 4138097: Single-Cell Analysis Reveals Critical Role of Macrophage Epsin in Regulating Origin of Foam Cell in Atherosclerosis
Authors: Arulsamy Kulandai Samy , Cui Kui , Chen Kaifu , Chen Hong
Published: November 2024

Background:
Excessive lipid aggregation in macrophages triggers foam cell formation, contributing to arterial plaque development. This underlies the chronic vascular condition of atherosclerosis like coronary heart disease and ischemic stroke. Epsins, endocytic adaptor proteins, are recognized as key accelerators of atherosclerosis progression, particularly in individuals adhering to a Western diet (WD). However, the intricate molecular mechanisms governing the role of epsins in foam cell formation, disease progression, and potential therapeutic interventions remain elusive. Here, we aim to probe the metabolic regulatory functions of epsins in atherosclerosis and design the potential treatment strategies.

Methods:
We established mouse models fed a WD (16 weeks), including ApoE-deficient (ApoE
-/-
) mice and macrophage-specific deletion of epsin in ApoE-deficient backgrounds (LysM-DKO/ApoE
-/-
). Foam cell formation is dramatically hindered in WD-fed LysM-DKO/ApoE
-/-
compared to ApoE
-/-
mice.

Results:
Single-cell transcriptomic profiling of aorta cells revealed 20 cell types, including seven VSMC subtypes, five macrophage subtypes, endothelial cells, and others. Pathway enrichment analysis showed that modulating VSMC1 is involved in inflammation and migration, while VSMC2 is associated with VSMC phenotype switching. We observed increased populations of modulating VSMC1, VSMC2, foamy-Trem2, and inflammatory macrophages in ApoE
-/-
mice, which decreased significantly in epsin-deficient mice. The RNA velocity analysis revealed that modulating VSMC2 transitioned towards macrophages with probabilities of 0.7 in ApoE
-/-
mice and 0.01 in LysM-DKO/ApoE
-/-
mice. Additionally, epsin deletion reversed endothelial cell dysfunction by preventing the endothelial-to-mesenchymal transition. Using MEBOCOST tool, we identified the cholesterol, glucose mediated cell-signals are downregulated in LysM-DKO/ApoE
-/-
. Moreover, enhanced inflammatory signals via ligands such as Il1b and C1qa in VSMCs are downregulated when epsin is depleted.

Conclusion:
Single-cell data analysis reveals that epsin deletion reduces foam cell formation and rewires VSMC cells function by inhibiting VSMC2 to macrophage transition. Cholesterol and glucose-mediated metabolic signals play a pivotal role in atherosclerotic lesion formation. Epsin deletion diminishes these metabolic, and inflammatory signals. Therefore, targeting epsin could offer a novel therapeutic strategy for treating atherosclerosis.
Abstract 4138112: A Case of Caseous Mitral Annular Calcification and the Utility of Multimodality Cardiac Imaging
Authors: Nguyen Amanda , English Carter , Ghasemiesfe Ahmadreza , Venugopal Sandhya
Published: November 2024

Background:
Mitral annular calcification (MAC) is a common incidental finding associated with advanced renal dysfunction, hyperlipidemia, hypertension, or abnormal calcium metabolism. Caseous mitral annular calcification (CMAC) is a less common MAC variant involving central liquefaction necrosis, which results in a paste-like substance consisting of calcium, fatty acids, and cholesterol.

Case description:
A 64-year-old female presented to clinic with chronic shortness of breath and fatigue that started after COVID-19 pneumonia in 2021. As part of the initial evaluation, a transthoracic echocardiogram (TTE) was done, which revealed moderate annular calcification, 3+ mitral valve regurgitation, and a 1.8x1.5 cm echogenic mass on the posterior mitral annulus, concerning for possible fungal vegetation. Further multimodality imaging was pursued. Transesophageal echocardiogram confirmed the presence of a 2.0x1.7 cm cystic mass but demonstrated normal mitral valve function. Cardiac MR further identified a 1.2x0.8x1.5 cm hypointense mass, with surrounding late gadolinium enhancement, suggesting an associated inflammatory/degenerative process. Gated cardiac CT scan showed a mass with ring-like dense peripheral calcification and low central attenuation. Overall, findings from multimodality imaging were most consistent with CMAC. In the present case, the patient was monitored conservatively, as her symptoms of shortness of breath improved, and she did not experience any associated complications.

Discussion:
The present case demonstrates an incidental finding of an echogenic mass on the posterior mitral annulus, later identified as CMAC. Initial imaging with TTE helps evaluate for CMAC. However, on TTE alone, CMAC is often misdiagnosed with other conditions, including intracardiac tumors, abscesses, vegetations, or thrombi, and more advanced imaging is often recommended. On cardiac MR, CMAC is usually hypointense due to the elevated calcium content and may have surrounding late gadolinium enhancement due to associated inflammation. On gated cardiac CT, CMAC presents with a hyperintense rim due to calcification and a hypointense center consistent with central necrosis. As in this patient, CMAC is usually a benign condition that can be monitored conservatively. Indications for invasive intervention include significant valvular dysfunction, embolization, or conduction abnormalities. Multimodal imaging can aid in appropriate diagnosis to mitigate unnecessary interventions.
Abstract 4138125: Interleukin-1 Antagonists in the Management of Recurrent Pericarditis due to Autoimmune Diseases: Beyond AIRTRIP and RHAPSODY
Authors: Bhalla Jaideep Singh , Saraswati Ushasi , Rosenzveig Akiva , Syed Alveena , Majid Muhammad , Klein Allan
Published: November 2024

Background:
Anakinra (AK) and Rilonacept (RL) are increasingly being used as steroid sparing agents in the management of recurrent pericarditis due to their antagonism of the IL-1 mediated innate immune activation. However, it is uncertain whether they would show a similar response in reducing recurrence of Autoimmune Pericarditis (AP), since this is mediated by the adaptive immune system and this cohort was excluded from the AIRTRIP/RHAPSODY trials.

Hypothesis:
IL-1 antagonists (IL-1#) maintain clinical remission in AP refractory to other disease modifying therapy (DMT).

Aims:
To evaluate the efficacy and safety of IL-1# in treating pericarditis associated with autoimmune diseases.

Methods:
We retrospectively analysed 31 adults at our Pericardial Center with AP that was refractory to treatment with standard DMT aimed at managing the underlying disorder and were started on AK/RL after shared decision making with the patient and their rheumatologist. Markers of disease activity (serologic/imaging) and adverse effects were obtained during the treatment period.

Results:
The cohort included 80% females with median age 51 y with ≥ 2 verified recurrences on standard DMT and treated with AK (68%)/RL (32%) for a median of 21 months. Majority of the patients had rheumatoid arthritis and inflammatory colitis. IL-1# therapy was associated with decreased number of flares, C-reactive protein levels, and late gadolinium enhancement on cardiac magnetic resonance imaging, the former 2 parameters reaching statistical significance. 6 cases of infection were noted; 2 required IL-1# cessation. No malignancies, major cardiovascular events or death was noted during follow-up.

Conclusions:
IL-1# (AK/RL) are associated with clinical improvement in patients with refractory AP, supporting the growing evidence from case reports in literature. This is the first study of this sample size analysing outcomes in patients with AP on IL-1#. This may suggest the presence of additional molecular immune pathways mediating recurrence in AP that need elucidation in future prospective studies.
Abstract 4138146: Heart Failure and Cardiomyopathy Mortality Trends and Disparities among Obese Populations: A 20-Year U.S. Study
Authors: Yeo Yong Hao , San Boon Jian , Ahmad Ela , Tan Min Choon , Sin Yuh Miin , Jani Milena , Bloomingdale Richard
Published: November 2024

Background:
The prevalence of obesity has been increasing over the past decades. While heart failure (HF) and obesity management evolve, real-world data on their population-level mortality benefits is lacking.

Objective:
Our study aimed to assess the HF and cardiomyopathy-related mortality trends among patients with obesity in the United States (U.S.) and disparities across demographics.

Methods:
We queried the CDC WONDER database among adults aged ≥ 25 from 1999 to 2019. We included patients in whom HF and cardiomyopathy were listed as the main cause of death, with obesity as a contributing cause of death. We calculated age-adjusted mortality rates (AAMR) per 100,000 individuals. We determined trends over time by estimating the annual percent change (APC) using the Joinpoint regression program. We evaluated the social vulnerability of U.S. counties (2014-2018) using the CDC/ATSDR SVI database.

Results:
There were 29,334 deaths related to HF and cardiomyopathy among patients with comorbid obesity. The overall AAMR increased from 0.41 (95% CI, 0.38-0.44) in 1999 to 0.94 (95% CI, 0.90-0.98) in 2019, with an APC of 3.78 (95% CI, 3.41-4.14, P<0.01). The percentage increase in the crude mortality rate of HF and cardiomyopathy among individuals with comorbid obesity was greater than that among those without comorbid obesity. Males had a higher AAMR than females (0.78 [95% CI, 0.77-0.79] vs 0.55 [95% CI, 0.54-0.56]). African Americans also had higher AAMR than Whites (1.35 [95% CI, 1.32-1.39] vs 0.62 [95% CI, 0.61-0.63]). The AAMR was higher in rural areas than in urban regions (0.76 [95% CI, 0.74-0.78] vs 0.66 [95% CI, 0.65-0.67]). The overall AAMR was higher in counties with social vulnerability index-Q4 (SVI-Q4) (most vulnerable) (1.08 [95% CI: 1.04-1.12]) compared to SVI-Q1 (least vulnerable) (0.63 [95% CI: 0.60-0.66]) with a risk ratio of 1.71 (95% CI: 1.61-1.83).

Conclusion:
Our study reveals the rising trend of HF and cardiomyopathy mortality in individuals with comorbid obesity. Males, African Americans, and individuals from rural regions had higher AAMR than their counterparts. This warrants the formulation of targeted healthcare policies for this vulnerable group.
Abstract 4138167: Comparative Efficacy Of Minimally Invasive Versus Standard Treatments For Intracerebral Hemorrhage: A Meta-Analysis and Systemic Review
Authors: Shafique Nouman , Ali Syed , Akbar Usman , Tariq Sheraz Ahmad , Mazhar Muhammad Saim , Umer Ahmed Muaaz , Ashfaq Fatima , Khan Ali Raza , Muhibullah Fnu , Shafique Adeena , Shafiq Iqra , Hasnain Haider , Ramzan Muhammad , nasir zeeshan , Talha Muhammad , Mustafa Faizan E , Nazam Imtiaz , khaliq muhammad , Ayub Muhammad , Sharma Saurabh
Published: November 2024

Background:
Intracerebral hemorrhage (ICH) has high morbidity and mortality. Traditional craniotomy causes significant trauma and lacks proven benefits. Minimally invasive techniques (MIT) like CT-guided thrombolysis, endoscopic, and neuronavigation surgeries show promise in reducing secondary neurotoxicity. Our meta-analysis compares MIT with standard treatments for supratentorial spontaneous intracerebral hematomas (SSICHs) to evaluate their effectiveness in improving clinical outcomes.

Methods:
We comprehensively searched PubMed, EMBASE, and Cochrane Library for studies published before June 1, 2024, comparing MIT versus standard treatment for ICH. Data were analyzed using R (v.4.3). Pooled proportions with 95% confidence intervals (CIs) were calculated using a random effects model. Odds ratios (ORs) and mean differences (MDs) with 95% CIs were used for dichotomous and continuous variables. Outcomes included overall survival, functional neurological outcome, hospitalization length, recurrent bleeding, volume reduction, and Glasgow Coma Scale (GCS) score at discharge.

Results:
We identified six studies, including 1,117 patients. There were 463 patients who underwent MIT and 654 patients who received standard treatment. The MIT group exhibited statistically significant increased odds of survival (OR: 1.98 [1.25, 3.15]; I2=26%; p=0.004) and functional neurological outcome (OR: 1.94 [1.27, 2.96]; I2=25%; p=0.002) compared to the standard treatment group. The MIT group demonstrated statistically significant lower length of hospitalization (MD: -2.89 [-4.49, -1.30]; I2=47%; p=0.0004) and better GCS score at discharge (MD: 1.50 [1.00, 2.00]; I2=0%; p<0.00001) compared to the standard treatment group. The MIT group also showed a trend towards more volume reduction (MD: 12.33 [-11.39, 36.05]; I2=99%; p=0.31) and lesser odds of recurrent bleeding (OR: 0.71 [0.25, 1.99]; I2=15%; p=0.52) compared to the standard treatment group, but these were not statistically significant.

Conclusion:
MIT show superior outcomes in survival, functional neurological status, hospitalization length, and GCS scores at discharge compared to standard treatments for SSICHs. While trends towards greater volume reduction and lower bleeding recurrence were observed, they were not statistically significant. Further research is needed to optimize MIT and confirm its benefits in larger, randomized trials.
Abstract 4138182: Evaluation of ACTION-ICU Score as a Predictor of Complications Requiring Intensive Care in a Mexican Cohort of Patients with Non-ST-Segment Elevation Myocardial Infarction
Authors: Alanis Naranjo Jose Martin , Rivera Hermosillo Julio Cesar , Villegas Mayoral Jose Evodio
Published: November 2024

Introduction:
The ACTION-ICU Score is a tool to assess the risk of complications associated with non-ST-segment elevation myocardial infarction (NSTEMI) requiring intensive care unit (ICU) admission. Limited studies have investigated the effectiveness of risk scores in predicting the need for ICU care in patients with NSTEMI. We evaluated the performance of the ACTION-ICU Score in Mexican patients with NSTEMI.

Methods:
A retrospective cohort study of patients over 18 years old who were admitted to a coronary care unit in Mexico City, Mexico, between January 1, 2017, and December 31, 2023, with a diagnosis of NSTEMI according to the fourth universal definition of myocardial infarction; patients with cardiac arrest or shock on admission were excluded from the study. The ACTION-ICU score was applied to all patients based on the collected data. The cut-off score for ICU admission is 5, with a 9.3% risk of complications. During hospitalization, the composite primary outcome included cardiac arrest, shock, heart block requiring a pacemaker, respiratory failure, stroke, or death. The score's performance was estimated with a conditional multivariable logistic regression analysis, and the area under the curve (AUC) was calculated.

Results:
Among 345 patients with NSTEMI, 41 (14.2%) developed the primary outcome. The most common complications were shock (12.5%) and respiratory failure (8.1%). Regarding the score, heart failure was the variable with a significant risk of developing the primary outcome [OR: 4.78; 95% CI 2.17-10.5, p-value <0.01]. A score of 0 to 5 points was present in 187 patients (54.2%), ten of whom (5.3%) developed the primary outcome. The score had an AUC of 0.77 [CI 0.64-0.97, p-value 0.01], better than the original study.

Conclusion:
The ACTION-ICU score identifies Mexican patients with NSTEMI who need ICU care, providing a valuable tool for predicting complications and implementing best practices in medical units with limited resources.
Abstract 4138690: A Case of Hypertrophic Cardimyopathy: Digenic Variants of Uncertain Significance Mutations in MHY7 and RYR2 Genes
Authors: Durukan Selina , Uzunoglu Ekin , Farahmandsadr Maryam , Soffer Daniel
Published: November 2024

Introduction:
Hypertrophic Cardiomyopathy (HCM) is primarily a disease caused by mutations in single genes, but around 5% of HCM patients, exhibit 2 (digenic) or more (oligogenic) causal mutations in the same gene or in different genes. We present a case of familial HCM with variants of uncertain significance (VUS) mutations in the MYH7 and RYR2 genes, highlighting the complexity of genetic inheritance and its implications on disease severity.

Case presentation:
A 40-year-old male presented with a history of hypertension, HCM, and two prior myocardial infarctions. He had syncope, non-sustained ventricular tachycardia, and a family history of sudden cardiac death (SCD) in his maternal grandfather. A dual-chamber ICD was placed for primary prevention of SCD because of his high-risk profile. Echocardiography demonstrated normal LV size and function with moderate asymmetric septal hypertrophy. Cardiac MRI indicated diffuse asymmetric hypertrophy and a 10.9% LV myocardial scar burden. Left heart catheterization revealed normal coronary arteries with LVOT gradient up to 60 mmHg, consistent with HCM. Genetic testing revealed VUS in the MYH7 (c.1305G>A, p.Met435Ile) and RYR2 (c.10528C>A, p.Arg3510Ser) genes (Figure 1). Further family genetic testing confirmed these VUS mutations in multiple relatives (Figure 2).

Discussion:
The identification of VUS mutations in MYH7 and RYR2 genes in multiple family members highlights the complexity of genetic inheritance in HCM. These findings underscore the challenges in clinical interpretation and risk stratification, as the co-occurrence of mutations in different genes may have synergistic effects on disease severity and phenotype expression. Comprehensive genetic evaluation, including family studies, is crucial for understanding the clinical significance of these mutations and guiding personalized management strategies. Further research is needed to elucidate the impact of VUS mutations on the clinical outcomes of HCM patients.
Abstract 4138835: Efficacy and Safety of Sodium-glucose Transporter 2 Inhibitors in Acute Decompensated Heart Failure Patients Concomitant with Physical or Cognitive Frailty: Finding from the WET-HF Registry
Authors: Naito Ayami , Nagatomo Yuji , Iwashita Midori , Kawai Akane , Ikegami Yukinori , Takei Makoto , Goda Ayumi , Kohno Takashi , Mizuno Atsushi , Nakano Shintaro , Sakamoto Munehisa , Kitamura Mitsunobu , Shiraishi Yasuyuki , Kohsaka Shun , Adachi Takeshi , Yoshikawa Tsutomu
Published: November 2024

Background:
Recent evidence suggests the efficacy and safety of sodium-glucose transporter 2 inhibitors (SGLT-2is) in heart failure (HF) patients. However, there still remain concerns in their use among patients with physical or cognitive frailty.

Methods:
West Tokyo Heart Failure (WET-HF) Registry is an ongoing prospective multicenter registry in Japan enrolling all patients who were hospitalized for acute decompensated heart failure. We retrospectively analyzed the impact of physical or cognitive frailty-related factors (FF) on the association of SGLT-2i prescription with long-term outcomes using the data of WET-HF (2018-23, n=5106). Patients without data of SGLT-2i prescription at discharge were excluded. Primary endpoint (PE) was defined as the composite of cardiac death and HF rehospitalization during 2 years after discharge.

Results:
At baseline 3208 of 4845 patients (66%) had FF defined by any of following 5 factors: BMI <18.5 kg/m
2
, Barthel index ≤85, clinical frailty scale ≥4, geriatric nutritional risk index (GNRI) <82, and a history of dementia. The study population was divided by prescription of SGLT-2is at discharge. SGLT-2i users (n=737) showed younger age (73 vs 80 years, P<0.001), higher number of male sex (67% vs. 57%, P<0.001), higher prevalence of HF with reduced ejection fraction (55% vs. 40%, P<0.001), and diabetes mellitus (63% vs. 26%, P<0.001) compared to SGLT-2i non-users. This trend was similarly seen in FF subgroup. SGLT-2i users showed significantly lower rate of PE compared to non-users (19% vs 23%, P=0.008, log-rank test). The results were directionally similar in the patients with FF (20% vs. 26%, P=0.006), but in those without FF there was no difference in PE between SGLT-2i users and non-users (17% vs. 16%, P=0.96). These associations persisted even after adjusting for patient background with a propensity score-based inverse probability of treatment weighting for SGLT-2i prescription (FF, HR 0.59 [0.39 – 0.91], P=0.016; No FF, HR 0.75 [0.47 – 1.20], P=0.23, P for interaction 0.48). At 1 year after discharge (follow up rate 61%), there was no difference in SGLT-2i continuation rate between FF and No FF groups (81% vs. 85%, P=0.14). The patients with FF who continued SGLT-2i showed no significant temporal changes in BMI, GNRI, or eGFR, whereas those without SGLT-2i showed significant decline in eGFR (P<0.001).

Conclusions:
SGLT-2is was safe and efficacious even for HF patients with FF in our retrospective analysis.
Abstract 4138908: Sex-Specific Differences During Heart Failure Development In Double Transgenic Cyclin T1/Gq Alpha Subunit Mice
Authors: Benkner Alexander , Magers Dominik , Hammer Elke , Ameling Sabine , Wenzel Kristin , Volker Uwe , Koenemann Stephanie
Published: November 2024

Background:
In an aging population, heart failure (HF) remains a leading cause of mortality worldwide. This study utilized genetically modified mice to investigate cardiac hypertrophy and HF, exploring potential age and sex-related differences. The focus was on understanding proteomic changes, functional impairment, and cardiac remodeling to gain deeper insights into the molecular intricacies of HF.

Experimental Approach:
Double transgenic (DTG) male and female mice overexpressing both Cyclin T1 and Gαq under the control of the cardiac-specific α-myosin heavy chain promoter, show pathological myocardial cell growth and develop hypertrophy, eventually progressing to HF. Comparative analyses were conducted between DTG mice and respective wild-type (WT) littermates at the age of 5 and 9 weeks (n=4 per group, time point and sex). Heart function was evaluated via small animal echocardiography. Proteomes of the left ventricles (LV) of DTG and WT mice were analyzed by mass spectrometry and altered proteins categorized using Ingenuity Pathway Analysis.

Results:
DTG mice showed a decrease in heart function over time. Independent of sex, DTG mice exhibited a significant decrease in left ventricular ejection fraction (LVEF) after 9 weeks compared to WT (DTG vs. WT: LVEF: 38.4±10.2% vs. 63.3±4.3%; p<0.001) and in relation to younger 5-week-old animals (DTG vs. WT: LVEF: 61.1±2.7% vs. 68.6±4%; p=0.16). Functional and morphological changes were clearly visible earlier in DTG males at 5 weeks compared to females. Also, LV proteomes showed differences between DTG and WT, and between sexes. The most and strongest changes in protein abundance (q<0.05, FC≥|1.5|) were observed after 9 weeks in DTG compared to WT, and much stronger in females (overall: 450↑, 437↓; males: 312↑, 347↓; females: 464↑, 463↓). Regarding age and sex differences, effects were again more pronounced at a younger age in males (5 weeks; altered proteins: 761 in males, 572 in females). These differences became even more apparent from further enrichment analyses of significantly altered proteins categorized into functional pathways such as energy metabolism and CVD-related categories.

Conclusion:
Female mice tend to be more resistant to a down-regulation of mitochondrial oxidative capacity during pathological hypertrophy at earlier stages of disease progression. These sex differences emphasize the complexity of HF, pointing to the need of sex-specific considerations in therapeutic approaches.
Abstract 4138915: Exploring mediation through major bleeding between direct oral anticoagulants and cardiovascular (CV) events
Authors: Yuan Zhong , Schuemie Martijn , Weaver James , Barnathan Elliot
Published: November 2024

Introduction:
Although extracranial major bleeding (EMB) is often transient and manageable with supportive care, there is concern that EMB may have a subsequent detrimental effect on CV outcomes. However, a causal relationship is unclear, because the association is often confounded by underlying disease and comorbidities. Clinical trial data for more comprehensive analyses via advanced modeling are limited.

Research Question:
What is the effect of rivaroxaban vs. warfarin on CV outcomes mediated through EMB?

Aim:
To determine the extent of the effect of rivaroxaban vs. warfarin on CV outcomes that is mediated through their differential impact on EMB using a novel, advanced modeling approach (EUPAS1000000168).

Methods:
Using 5 US observational databases from routine clinical practice (01-11-2010 to 31-12-2022), adult patients with non-valvular atrial fibrillation (NVAF) were identified to establish the target and comparator cohorts, with 1
st
exposure as index date. Treatment balance was achieved by matching on propensity scores derived from large-scale regularized regression. Cox proportional hazards models estimated the main effect on CV outcomes (myocardial infarction, ischemic stroke, and composite endpoint) for rivaroxaban vs warfarin, with target and comparator time-at-risk right-censored at therapy end or switch, event occurrence, or database observation end. The EMB mediation effect on outcomes was estimated by including EMB as time-varying covariate, while controlling mediator-outcome confounding by including a mediator risk score in the outcome model. Comparative analyses were conducted only when pre-specified diagnostics passed for covariate balance, equipoise, and systematic error estimated through negative controls.

Results:
In 5 databases, 378,384 rivaroxaban initiators were matched to 601,174 warfarin initiators with NVAF. Common comorbidities included hypertension, hyperlipidemia, coronary artery disease, and heart failure. Main effects and indirect effects (mediation effects) are in Table A.

Conclusion:
This analysis suggested that EMB had no impact on the effect of rivaroxaban vs. warfarin on CV outcomes. A limitation is that EMB occurrence and CV events after EMB were limited, which reduced mediation impact.
Abstract 4138919: Evaluating Perioperative Colchicine's Influence On New-Onset Heart Block After Transcatheter Aortic Valve Implantation: A US Multicenter Retrospective Analysis
Authors: Abdelsayed Kerollos , Amer Basma , Fouad Michele , Elfert Khaled , Thangjui Sittinun , Banour Sandi , Abdelazeem Basel
Published: November 2024

Background:
New-onset heart block (NOHB) is a frequent early complication following transcatheter aortic valve intervention (TAVI), partially driven by mechanical edema. Colchicine, known for its anti-inflammatory properties and efficacy in reducing myocardial infarction in coronary artery disease, has never been studied for its effects on NOHB post-TAVI.

Methods:
This study used the TriNetX database (January 2013 to May 2024) to compare patients receiving colchicine (at least one dose within two days before and up to 12 days after their first TAVI) with those never exposed to colchicine up to one year after the procedure. A propensity score-matched (PSM) analysis controlled for baseline demographic and clinical characteristics (figure 1A). Outcomes included NOHB in addition to all-cause hospitalizations, all-cause mortality, new-onset atrial fibrillation (NOAF), acute coronary syndrome (ACS), and stroke at one and six months post-TAVI and were assessed through the risk ratio (RR) and 95% confidence interval (CI).

Results:
The control group included 49,384 patients, while the colchicine group included 725. After PSM, 712 patients were included in each group; 36.1% and 40.3% were females. The mean age was 77.8 (±8.9) and 78.1 (±8.8) years, respectively. Colchicine was associated with a significant reduction of NOHB at one month (RR= 0.64, 95% CI [0.49; 0.83],
p=0.001
) and six months (RR= 0.61, 95% CI [0.48; 0.78],
p<0.0001
) post-TAVI. Similarly, all-cause hospitalizations and mortality were significantly lower in the colchicine group at one month (RR= 0.65, 95% CI [0.60; 0.71],
p<0.0001
; RR= 0.41, 95% CI [0.21; 0.80],
p=0.007
, respectively) and six months (RR= 0.96, 95% CI [0.64; 0.74],
p<0.0001
; RR= 0.67, 95% CI [0.46; 0.97],
p=0.03
, respectively). Other postprocedural complications were comparable between the groups at one and six months (figure 1B). Sensitivity analysis revealed an E-value of 2.26 at one month and 2.4 at six months for the RR of NOHB.

Conclusion:
Perioperative colchicine was associated with reduced risk of NOHB, all-cause hospitalization, and all-cause mortality at one and six months after TAVI. However, it was not associated with reduced postoperative risk of NOAF, ACS, or stroke at one or six months.
Abstract 4138936: Outcomes of Over 1,000 Heart Transplants Using Donation After Circulatory Death Donors in the United States
Authors: Bhandari Krishna , Kwon Jennie , Uehara Atsuko , Sitsis Sophia , Sollie Zachary , Inampudi Chakradhari , Carnicelli Anthony , Rao Vishal N. , Houston Brian , Tedford Ryan , Kilic Arman
Published: November 2024

Introduction:
Heart transplantation (HT) with donation after circulatory death (DCD) donors has been increasing exponentially since its resurgence in the US. The aim of this study was to evaluate national outcomes of DCD HT.

Methods:
Adult HT recipients from 2019-2023 were identified from the United Network Organ Sharing registry. Patients were categorized based on donor-type (donation after brain death [DBD] or DCD). Kaplan-Meier and multivariable Cox regression analyses were used for survival. A propensity-matched analysis was also performed. A further sub-analysis was conducted comparing outcomes of DCD HT using normothermic regional perfusion (NRP) versus direct procurement and perfusion (DPP).

Results:
Among 19,684 HTs identified, 14,122 DBD and 1,139 DCD were included. The number of DCD HT increased from 7 in 2019 to 534 in 2023. In unadjusted analysis, 30-day (97.1% vs 96.7%, p=0.46) and 1-year (91.2% vs 90.5%, p=0.59) survival were comparable between DBD vs. DCD donors, although 3-year survival was worse in DCD recipients (DBD 83.7% vs DCD 76.8%, p=0.05; DCD multivariable HR 1.25, 95% CI 1.02-1.54; p=0.03). Similar findings were observed in the propensity-matched analysis, where DCD recipients had worse 1- and 3-year survival, findings that were confirmed after risk-adjustment (Figure). In sub-analysis comparing NRP versus DPP, unadjusted survival was comparable at all time intervals although there was a trend towards improved survival with NRP at 3-years (NRP 85.7% vs DPP 74.4%, p=0.08; NRP multivariable HR 0.63, 95% CI 0.39-1.02; p=0.06).

Conclusions:
This represents the largest real-world series to date of DCD HT and associated outcomes. DCD HT has increased substantially in the past several years and now comprises 15% of all HT performed in the United States. Although early outcomes are comparable with DBD donors, mid-term survival was worse by use of DCD, warranting further research. Although not statistically significant, use of NRP technique when using DCD for HT may confer a survival benefit.
Abstract 4138949: Type 2 Diabetes is Not a Coronary Artery Disease Risk Equivalent: Longterm Results from a Prospective Cohort Study on Patients Who Underwent Coronary Angiography
Authors: Plattner Thomas , Larcher Barbara , Mader Arthur , Vonbank Alexander , Leiherer Andreas , Muendlein Axel , Drexel Heinz , Saely Christoph H
Published: November 2024

Type 2 Diabetes (T2DM) and pre-existing coronary artery disease (CAD) are strong and independent risk factors for cardiovascular events, and data from large cohort studies suggest that the cardiovascular risk conferred by T2DM in the absence of CAD is equivalent to that conferred by CAD in the absence of T2DM. However, because the presence of CAD in these studies was defined clinically rather than by visualization, unrecognized subclinical CAD in T2DM patients may have biased results.

We therefore prospectively investigated patients with T2DM and non-diabetic subjects in whom the baseline CAD state was diagnosed angiographically. We recorded cardiovascular events over a follow-up period of 22 years in a large cohort of 1819 patients undergoing coronary angiography for the evaluation of established or suspected stable CAD.

From our patients, 595 had neither significant CAD nor T2DM (CAD-/T2DM-), 171 had T2DM but not significant CAD (CAD-/T2DM+), 701 had significant CAD but not T2DM (CAD+/T2DM-) and 352 had both T2DM and significant CAD (CAD+/T2DM+). The incidence of cardiovascular events was lowest in CAD-/T2DM- patients (24.7%). Compared to this group it was significantly higher in CAD-/T2DM+ patients (36.1%; p<0.001) and in CAD+/T2DM- patients (50.8%; p<0.001) and highest (p=0.001) in CAD+/T2DM+ patients, in whom it was higher than in CAD-/T2DM+ (p<0.001) or CAD+/T2DM- (p=0.001) patients. Importantly, CAD+/T2DM- patients were at a significantly higher risk of cardiovascular events than CAD-/T2DM+ patients (p<0.001). In Cox regression analysis the risk increase conferred by CAD was higher (adjusted (HR 2.35 [1.92-2.89]; p<0.001) than that conferred by T2DM (adjusted HR 1.54 [1.33-1.78]; p< 0.001).

From our long term results we conclude that angiographically diagnosed CAD is a stronger predictor of future cardiovascular events than T2DM. T2DM is not a CAD risk equivalent.
Abstract 4138967: SLPI and Serpin E1 differentiate between and can be used as AKI biomarkers in obese and non-obese patients
Authors: Wozniak Marcin , Brown Naomi , Pan Haiyan , Horley Barbara , Joel-David Lathishia , Aujla Hardeep , Murphy Gavin , BIN YANG Bin
Published: November 2024

Background:
Acute kidney injury (AKI) is among the most common complications after cardiac surgery, with an 18% prevalence and is associated with an increased risk of death. Cardiopulmonary bypass surgery generates danger-associated molecular patterns that trigger a release of proinflammatory molecules that can lead to AKI. Obesity is also associated with chronic low-grade inflammation and an increased risk for AKI. We investigated the utility of inflammatory molecules in the diagnosis of AKI in obese and non-obese cardiac surgery patients.

Methods:
A panel of 13 circulating plasma molecules, including CXCL1, CXCL10, CXCL13, CCL22, IL-5,6,8,10,16, SLPI, TIM1, Properdin, Serpins E1 and A3, was measured using MAGPIX. The samples were collected from 95 MaRACAS patients (NCT02315183) before and 6-72 hours (h) after surgery. Obesity was defined as BMI>=32, based on our previous study.

Results:
There was no significant difference in the incidence of AKI between obese (46%) and non-obese patients (58%). The levels of the selected molecules were compared between AKI and non-AKI groups in patients with and without obesity. In obese patients with AKI, the levels of serpin E1 were lower before surgery (22.16 vs 40.94ng/mL, q=0.03) and higher 6h post-surgery (49.26 vs 21.65ng/mL, q=0.02), while properdin was lower 72h post-surgery (11.12 vs 14.35ng/mL, q=0.01). In the non-obese group, CXCL10 was higher in the AKI group 6-48h post-surgery, peaking at 6h (218.5pg/mL vs 131.38pg/mL, q=0.02); CXCL13 was higher at 6h (435.78 vs 291.0pg/mL, q=0.04) and 24h (215.18 vs 157.49pg/mL, q=0.04); IL-16 was higher at 6h (256.01 vs 174.44, q=0.04) and 24h (344.94 vs 174.02, q=0.02); and SLPI was higher 6-72h post-surgery, peaking at 6h (50.44 vs 33.53 at 6h, q<0.01). ROC AUC analyses showed that Serpin E1 had a diagnostic value for AKI in obese patients pre (75.6%, 58.3%-92.8%) and 6h post-surgery (80%, 64.6%-95.4%); while SLPI had a diagnostic value in non-obese patients 6h after surgery (75.0%, 62.2%-87.8%).

Conclusions:
AKI leads to different expression levels of proinflammatory molecules in obese and non-obese patients undergoing cardiac surgery. SLPI and Serpin E1 have diagnostic potential as biomarkers, but should be validated in larger cohorts.
Abstract 4139025: The Impact of Diastolic Function on Cardiac Outcomes in Patients with Cirrhosis after Liver Transplantation
Authors: Wadid Mark , Bedrosian Aram , Lessey Candace , Shah Jui , Dani Sourbha , Diaco Maurizio , Gadey Gautam , Qamar Amir , Malik Raza , Rowin Ethan
Published: November 2024

Introduction:
Diastolic dysfunction may prognosticate adverse cardiovascular outcomes post-liver transplantation (LT). However, the impact of diastolic dysfunction on post-transplant outcomes has not been thoroughly investigated. We sought to determine the prognostic utility of baseline echocardiographic abnormalities on post-LT outcomes.

Methods:
A retrospective cohort study was conducted on adult patients who underwent LT at Lahey Hospital (2015-2020), followed until 2023 for major adverse cardiovascular events (MACE) and mortality. Diastolic dysfunction was assessed per 2016 ASE guidelines: septal e' < 7 cm/s; lateral e' < 10 cm/s; E/e' ≥ 15; Left atrial volume index > 34 ml/m
2
; Tricuspid Regurgitation velocity > 2.8 m/s. with 0 or 1 abnormal parameter considered normal, 2 abnormal parameters were categorized as indeterminate, and ≥3 as diastolic dysfunction.

Results:
LT was performed in 423 patients (mean age 56.4 ± 9.62; 67.4% male), mainly for alcohol cirrhosis (36%), metabolic dysfunction-associated steatotic liver disease (16%), and liver malignancy (15%). Pre-operative echocardiography was conducted a median of 3 days before LT evaluation. Ejection fraction (EF) was 65 ± 4.5%; no patient had EF < 50%. Diastolic dysfunction was noted in 17 patients. 363 had normal diastolic function and 44 indeterminate diastolic function.

Over 3 years post-LT, 70 patients died (5 cardiovascular deaths), and 48 experienced MACE: 21 hospitalizations for acute heart failure, 8 nonfatal myocardial infarctions, 14 cerebrovascular events, and 5 cardiovascular deaths. Mortality and MACE rates did not differ significantly between patients with normal diastolic function (16.8% and 13.2%), indeterminate (13.6% and 9.1%), or diastolic dysfunction (18.8% and 18.8%, p=0.84 and p=0.58 respectively). However, a higher proportion of patients who experienced MACE had a history of atrial fibrillation (AF) (33% vs. 14%, p < 0.001) and CAD before LT listing (31% vs. 9%, p < 0.001), despite 60% of patients with MACE and CAD undergoing revascularization.

Conclusion:
In this cohort, diastolic dysfunction did not appear predictive of all-cause mortality or adverse cardiac events post-LT, suggesting it may not be a sensitive marker for post-LT cardiovascular complications. In contrast, patients with prior AF and CAD history are at higher risk, indicating a need for further studies to evaluate if these conditions should preclude LT.
Abstract 4139027: Glucagon-like Peptide-1 Receptor Agonist Use and Cardiac Outcomes in Patients with End Stage Kidney Disease
Authors: Catanese Benjamin , Miller Cameron , Wolf Myles , Edmonston Daniel
Published: November 2024

Background:
Despite the substantial cardiovascular (CV) risk experienced by people with end-stage kidney disease (ESKD), few medications improve CV outcomes in this population. Glucagon-like peptide-1 receptor agonists (GLP1RA) improve CV outcomes in CKD, and several are safe for use in ESKD, but no outcomes trial has studied GLP1RA in ESKD. We hypothesize that CV outcomes will be improved in people with ESKD and type 2 diabetes mellitus (T2D) who initiated GLP1RA as compared to dipeptidyl peptidase-4 inhibitors (DPP4i), an agent that comparably lowers glucose but has not been shown to improve CV outcomes.

Methods:
We analyzed electronic health records, claims, and Medicare Part D data from the United States Renal Data System between 2011 and 2021 to identify new users of GLP1RA or DPP4i after initiation of dialysis. We restricted the cohort to patients with T2D based on ICD codes and used 2:1 propensity score matching of DPP4i to GLP1RA users based on 22 covariates. The primary outcome was a modified major adverse cardiovascular events (MACE) composite of myocardial infarction (MI), stroke, and all-cause mortality. We applied cause-specific Cox proportional hazard models and Fine-Gray subdistribution hazard models to account for competing risks to analyze the primary outcome and its components.

Results:
The matched cohort included 10,196 DPP4i and 5976 GLP1RA initiators. The median age was 59 years, 49% were women, and 29% were of Black race. Compared to DPP4i initiators, GLP1RA initiators experienced a significantly lower risk of MACE (HR 0.92, 95% CI 0.89 – 0.96; Table). The risk of nonfatal MI or stroke was also significantly lower for GLP1RA initiators (HR 0.91, 95% CI 0.87-0.95). All-cause mortality did not differ based on cause-specific hazard modeling (HR 0.97, 95% CI 0.88-1.06), but was significant based on subdistribution hazard modeling (HR 0.86, 95% CI 0.79-0.94).

Conclusion:
Initiation of GLP1RA was associated with significantly lower risk of MACE in patients with T2D and ESKD compared to DPP4i.
Abstract 4139063: Sex Differences in Age of Onset of Cardiovascular Disease and Subtypes: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Freedman Alexa , Colangelo Laura , Lewis Cora , Schreiner Pamela , Khan Sadiya , Lloyd-Jones Donald
Published: November 2024

Introduction:
Historically, coronary heart disease (CHD) has been reported to develop about ten years earlier in males than females. However, whether this gap has narrowed in a contemporary sample and whether similar sex differences in age of onset exist for other cardiovascular disease (CVD) subtypes (stroke and heart failure [HF]) that are becoming more common is not known.

Methods:
Participants were enrolled in the CARDIA study between the ages of 18-30 years in 1985-1986. Sex differences in the cumulative incidence functions of premature CVD (defined as onset before 65 years), overall and for each subtype including CHD, HF, and stroke, were compared using Gray’s test.

Results:
Among 5115 participants (54.5% female, 51.6% Black), the mean age at study enrollment was 24.8 years (SD: 3.7). Over a median follow-up of 34.0 years (IQR 33.8, 35.7), cumulative incidence of total CVD, CHD, and HF was significantly higher in males compared with females (p<0.05 for all). For total CVD, males reached an incidence of 5% at a younger age than females (50.1 versus 57.3 years, Figure). CHD was the most frequent CVD subtype, and an incidence of 2% occurred at a younger age among males compared with females (48.3 vs. 58.5). For HF, an incidence of 1% occurred among males by age 48.4 compared with 51.7 for females. For stroke, an incidence of 2% occurred at similar ages for males and females (56.3 and 55.1 years). Cumulative incidence for CVD, CHD, HF, and stroke, respectively, by age 50, was 5.0%, 2.7%, 1.3%, and 1.3% for males and 3.0%, 1.0%, 1.0%, and 1.3% for females. In a secondary race-stratified analysis, Black males and females reached cumulative incidences of 6.3% and 4.5%, respectively, for total CVD by age 50, in comparison to 3.7% and 1.4% among White males and females.

Conclusion:
Males reached 5% incidence of total CVD seven years earlier than females, with the greatest difference observed in age of onset for CHD. Age of onset for HF and stroke were similar between males and females. This may inform sex-specific prevention strategies for young adults.