bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4143538: A Predictive Tool and Diagnostic Screening Algorithm for the Identification of Transthyretin Amyloid Cardiomyopathy in High-Risk Patient Populations
Authors: Chai Jocelyn , Starovoytov Andrew , Campbell Christine , Hawkins Nathaniel , Virani Sean , Luong Michael , Straatman Lynn , Kiess Marla , Worsley Daniel , Sathananthan Janarthanan , Fine Nowell , Davis Margot
Published: November 2024

Introduction:
Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed disease that may result in heart failure (HF), arrhythmias, and valvular disease. Our aim was to develop (1) screening criteria to identify high-risk patients for ATTR-CM and (2) our own predictive tool of ATTR-CM.

Methods:
This was a prospective observational registry at 2 academic sites in Canada. We designed screening criteria to identify high-risk patients in HF, atrial fibrillation, transcatheter valve clinics, and in cardiologist’s offices from January 2019-December 2022. Patients >60 years were included if one of several screening criteria was met and they were referred for pyrophosphate scan by the cardiologist. Univariate and multivariate logistic regression were used to identify predictive clinical, imaging, and biochemical characteristics.

Results:
In total, 2500 patients were screened, and 200 patients were enrolled with a follow-up duration of 3 years. The mean age was 78 years and 65% were male. Forty-six (23%) had a diagnosis of ATTR-CM and 7 (4%) were diagnosed with AL-amyloidosis. ATTR-CM patients were older (83±7 vs. 77±8; p<0.001), predominantly male (80 vs. 60%, p=0.01), symptomatic (NYHA III-IV) (46 vs. 19%; p<0.001) and had higher NT-proBNP (3633 vs. 2018; p=0.01). Fewer were on beta-blocker (p<0.001) and renin-angiotensin inhibitors (p=0.01), and more were on amiodarone (p=0.008). They had larger left ventricular posterior wall diameters (14±3 vs. 11±2; p<0.001). On electrocardiogram, ATTR-CM patients had lower voltages (37 vs. 4%; p<0.001) and more atrioventricular blocks (39 vs. 19%; p=0.02). Tissue doppler (E/e’) was higher in ATTR-CM patients (18±7 vs. 14±6; p=0.001). The positive predictive value (PPV) for our screening criteria ranged from 16-38%, with the highest PPV and negative predictive value (NPV) for age ≥70 years and new HF (PPV 38%, NPV 95%). We identified 5 key predictors of ATTR-CM to develop a practical tool for clinicians with a score of ≥7 meeting criteria for further testing (Figure 1). This tool had a sensitivity of 89%, specificity of 85%, PPV of 64%, NPV of 96%, and an area under receiver operating characteristic curve of 0.9.

Conclusion:
Broad screening criteria applied to high-risk patient populations yielded new ATTR-CM diagnoses in 23% of patients. Screening tools for ATTR-CM can be used to help clinicians identify patients who should undergo further testing. Further studies are needed to validate our predictive tool.
Abstract 4143565:
Outstanding Research Award in Pediatric Cardiology:
Prevalence, evaluation, and treatment of neurodevelopmental disorders in publicly insured children with critical congenital heart disease in the first 5 years after infant heart surgery
Authors: O'Meara Daniel , Henson Brandi , Rollins Caitlin , Gauvreau Kimberlee , Berry Jay , Hall Matthew , Newburger Jane
Published: November 2024

Background:
Survivors of infant heart surgery are at greater risk for neurodevelopmental (ND) disorders. Rates of ND diagnoses (dx) and resource utilization are derived from referral centers or single-state studies, with few multi-state data on diagnosis and utilization across inpatient and outpatient settings.

Methods:
We characterized ND dx, medications, screening/evaluation, and non-medical therapies up to 5 years of life among children born in 2016-2020 in the Merative MarketScan Medicaid Claims database from 12 anonymized states. Surgical complexity was assessed with RACHS-2 category. Cox proportional hazards regression was used to identify risk factors for time to 1) first ND dx and 2) first ND evaluation/intervention.

Results/Data:
Among 3,147 patients enrolled for a mean 30.5 months, surgery was neonatal in 48%; 23% had a genetic dx; and highest RACHS-2 category was 1= 30%, 2=29%, 3=13%, 4=18%, and 5=10%. Brain imaging was performed in 13%, most commonly MRI (8%). Without adjusting for variable follow-up, the proportion with ≥1 ND dx was 41%, most commonly Communication Disorder (25%), Global Developmental Delay (15%), and Motor Disorder (19%). At latest follow-up, 85% had received ≥1 ND service and 78%, ≥1 direct intervention (ST, OT, and/or PT). Brief ND screening was completed in >58%, but few had psychological/neuropsychological (6.6%) or comprehensive developmental (8.5%) evaluation. Use of stimulants (0.5%), anti-depressants (0.1%) and antipsychotics (0.2%) were uncommon, but anticonvulsants had been used in 7.3%. Independent risk factors for earlier time to any ND dx were Black (p=0.043) or Hispanic (p=0.032) vs. White race/ethnicity, and RACHS-2 Category 4 (p=0.002) or 5 (p=0.007) vs. 1. Independent risk factors for shorter time to first ND evaluation or intervention included RACHS-2 Classes 2 (p=0.012), 4 (p<.001), and 5 (p<.001). Birth sex and genetic abnormalities were not significant predictors of ND dx or utilization. Data for center and region were not available.

Conclusions:
The prevalence of ND dx and utilization of ND services was high up to age 5 years in this population-based sample of publicly insured children who underwent infant heart surgery. Rates of developmental screening were comparable to those in general pediatric samples, but few children received formal ND evaluations, falling short of AHA recommendations for universal developmental evaluation.
Abstract 4143599: Subpopulation Benefits and Adverse Events of Prophylactic Methylprednisolone for Infant Heart Surgery: An Analysis of the STRESS Trial
Authors: Sunthankar Sudeep , Hill Kevin , Jacobs Jeffrey , Baldwin Scott , Jacobs Marshall , Li Jennifer , Graham Eric , Blasiole Brian , Husain Adil , Bleiweis Mark , Mettler Bret , Benscoter Alexis , Wald Eric , Karamlou Tara , Van Bergen Andrew , Eghtesady Pirooz , Scott John , Anderson Brett , Alfieris George , Vener M D David , Kannankeril Prince
Published: November 2024

Background:
The Steroids to Reduce Systemic Inflammation after Infant Heart Surgery (STRESS) trial randomized 1200 infants undergoing cardiac surgery with cardiopulmonary bypass to prophylactic intraoperative methylprednisolone (MP) versus placebo.

Aims:
Evaluate benefits and harms associated with MP in subset populations.

Methods:
STRESS participants were categorized based on STAT Mortality Category (1-3 and 4-5), age (neonate ≤ 30 days< non-neonate), prematurity (< 37 weeks gestation) and any chromosomal or syndromic diagnoses (CSD). Key postoperative outcomes included any steroid administration (< 72 hours after surgery), peak blood glucose (<72 hours), insulin use (< 24 hours), acute kidney injury (AKI), prolonged mechanical ventilation (>7 days), thrombosis, and infections.

Results:
The cohort consisted of 30% (364/1200) neonates, 16% (193/1197) premature, and 81% (969/1197) STAT 1-3 operations. Stratified analyses demonstrated notable beneficial effects with MP including reduced use of postoperative hydrocortisone in neonates (OR 0.39 [0.25-0.60]), those following STAT 1-3 (OR 0.65 [0.47-0.91]) and STAT 4-5 operations (OR 0.57 [0.34-0.97]), term infants (OR 0.62 [0.47-0.83]), and those without CSD (OR 0.63 [0.46-0.86]). MP associated with lower thrombosis occurrence among neonates (OR 0.37 [0.16-0.87]) and term infants (OR 0.38 [0.19-0.75]). Notable adverse associations with MP included increased postoperative peak blood glucose levels and insulin use (all subgroups, P<0.01), increased thrombosis events among premature infants (8/100 vs. 0/93, P=0.005), and increased AKI following STAT 1-3 operations (OR 1.35 [1.03-1.77]) and in neonates (OR 1.55 [1.02-2.37]). The AKI association was not significant after adjusting for preoperative renal dysfunction and peak blood glucose. No increase in overall infection or reduction in prolonged mechanical ventilation were detected in any subgroup with MP.

Conclusion:
Prophylactic intraoperative MP has beneficial and adverse effects in infants undergoing cardiac surgery. The reduction in hydrocortisone, a common treatment for low cardiac output syndrome, and absence of increased infection rates are arguments for prophylactic intraoperative MP. However, MP was associated with increased peak blood glucose levels and a neutral to harmful association with odds of AKI. Though the latter was not significant after adjusting for peak blood glucose, which suggests steroid induced hyperglycemia may contribute to AKI.
Abstract 4143606: Ficolin-1 Genetic Polymorphisms in Chronic Chagasic Cardiomyopathy
Authors: Fontana Pamela , Andrade Fabiana , Lidani Karita , Placido Helena , Catarino Sandra , de Messias-Reason Iara
Published: November 2024

Background:
Chagas disease (CD) is an infectious disease caused by the protozoa
Trypanosoma cruzi
, affecting around 6-7 million people in Latin America. Although most infected individuals remain asymptomatic throughout their lives, annually 2-5% of them progress to chronic chagasic cardiomyopathy (CCC), digestive megasyndromes, or both. Ficolins are innate immunity proteins that play a crucial role in the lectin pathway (LP) of complement activation. They recognize pathogen-associated molecular patterns and mediate the clearance of apoptotic cells and cellular debris. Genetic polymorphisms of components of LP have been associated with clinical forms of CD; however, the relationship between Ficolin-1 (
FCN1
) gene polymorphisms and CD remains unclear.

Hypothesis:
We hypothesize that polymorphisms in the
FCN1
gene, previously related to its expression, are associated with clinical forms of CD, possibly impacting LP activation.

Goals:
To investigate the association of genetic variants of the
FCN1
gene with the clinical forms of chronic CD.
Methods:
We evaluated three single-nucleotide polymorphisms (SNPs): rs2989727G>A (c.-1981G>A), rs17039495 (-399G>A) and rs10858293 (+33G>T) by sequence-specific amplification in 200 patients with chronic CD (23.5% asymptomatic, 52% CCC, 10% digestive form, and 14.5% cardiodigestive form) from Southern Brazil, and 210
T. cruzi
seronegative controls. Logistic regression models were adjusted for sex, age, and self-identified ethnicity, followed by Bonferroni correction.

Results:
The haplotypes GGG, AGT, AGG, GAT, and AAT were more frequently found in patients, while GGG, AGT, AGG, and AAT were more common in controls. We observed a higher frequency of the G allele (p=0.004; OR 1.49; 95% CI 1.14, 1.99) of SNP rs2989727 and the GG genotype (p=0.010; OR 1.82; 95% CI 1.10, 3.03) in CD patients, particularly those with symptomatic forms (p=0.008; OR 1.51; 95% CI 1.11, 2.03; and p=0.012; OR 2.05; 95% CI 1.17, 3.59) and CCC (p=0.013; OR 1.54; 95% CI 1.10, 2.16, and p=0.013; OR 2.16; 95% CI 1.18, 3.97), compared to the control group.

Conclusion:
The
FCN1
rs2989727 variant is associated with chronic CD and CCC, likely due to its impact on
FCN1
gene expression.
Abstract 4143615: Does the Prognostic Value of Zero Coronary Artery Calcium Score Vary by Patient Sex?
Authors: Anderson Jeffrey , Collingridge Dave , Le Viet , Iverson Leslie , Muhlestein Joseph , Bair Tami , Knight Stacey , Mason Steve , Knowlton Kirk , Horne Benjamin
Published: November 2024

Background:
A coronary artery calcium score of zero (CAC=0) is generally accepted as a marker of a very low 5y risk for coronary events. However, whether the prognostic value of CAC=0 varies by sex is unclear. For example, non-atherosclerotic causes of coronary ischemia present more often in women, including spontaneous coronary artery dissection and microvascular angina, which may be undetected by CAC. Further, CAC is performed at a later age in women. Whether these factors impact the utility of CAC=0 in women vs men is uncertain.

Methods:
We tested whether the prognostic value of CAC=0 differs by sex. We searched the Intermountain Health electronic medical record (eMR) database for patients (pts) at primary coronary risk who underwent positron emission tomography/computed tomography (PET/CT) stress testing and had a zero CAC score. We assessed coronary prognosis (i.e., coronary death [CD] or non-fatal myocardial infarction [MI]) during follow-up. Primary events were adjudicated by chart review. We compared outcomes in women vs. men. Given the small number of events, chi-square rather than time-to-event analyses were performed. We also compared all-cause death or MI rates in those with CAC=0 vs. CAC>0 by sex.

Results:
The eMR search identified19,495 women and 20,523 men undergoing PET/CT who were at primary coronary risk. Of these, 7967 (19.9%) had CAC=0 on CT. Of CAC=0 patients, 5400 (67.8%) were women and 2567 (32.2%) were men. Overall age averaged 60.5y (SD 12.0) in women and 53.8y (SD 12.6) in men. In total, 13 events occurred (MI=12, CD=1) over a follow-up of 2.1y (SD 1.6). By sex, 7 events (0.13%) occurred in CAC=0 women and 6 (0.24%) in men (p=0.28). Rates of all-cause death or non-fatal MI comparing CAC=0 to CAC>0 were 3.3% vs 9.5% in women and 3.3% vs 10.2% in men (both p<.0001). MI with no obstructive coronary artery disease (MINOCA) constituted 3/7 MI’s in women and 1/5 MI’s in men.

Conclusions:
In this large, integrated healthcare system experience of symptomatic pts at primary coronary risk undergoing PET/CT, a zero CAC score predicted an excellent prognosis for coronary death or non-fatal MI in both sexes. CAC=0 was more frequently observed in women despite an older average age. Rates of coronary events were at least as low in women as in men, with a trend to more MINOCA events and fewer obstructive coronary events in women. Further, a zero calcified plaque burden predicted a 3-fold lower risk of all-cause death or MI in both sexes.
Abstract 4143622: Efficacy of Semaglutide in Patients with Obesity and Heart Failure With Preserved Ejection Fraction (HFpEF): A Systematic Review&Meta-Analysis
Authors: Mylavarapu Maneeth , Gandapur Asad , Abarca Yozahandy , Roshni Prarath , Fatima Husna , Contreras Vazquez Samantha , OBI OGECHUKWU , Siddiqui Muhammad Areeb , Huda Noor ul , Lysak Yuliya , Mowo-wale Adetola
Published: November 2024

Introduction:
Obesity-related heart failure in patients is often associated with high symptom burden. However, no treatments have been proven to specifically target obesity-related heart failure with preserved ejection fraction (HfpEF).

Objective:
The objective of this study is to evaluate the efficacy of semaglutide in patients with obesity and HfpEF.

Methods:
The study was by the PRISMA guidelines. Studies reporting endpoints of semaglutide in patients with obesity and HfpEF were included. The outcomes included percentage weight change and adjudicated heart failure events. Both random and common effects models were used for the data analysis. The random intercept logistic regression model was used to compute the proportions, and the Peto method was used to compute the odds ratios. A p-value ≤ 0.05 was considered significant.

Results:
In total, three studies with 1463 patients with obesity and HfpEF were included in the study. The mean age of the patients was 68.8 ± 3.47 years. 50.7% of the patients were females. Patients who received Semaglutide had statistically higher odds of 10% weight reduction (OR 6.35; 1.54-26.21; p<0.00001) and 15% weight reduction (OR 9.44; 2.91-30.60; p<0.0001) when compared to placebo. Additionally, patients who received Semaglutide had lower odds of adjudicated heart failure event (OR 0.32; 0.15-0.67; p=0.35) when compared to patients on placebo.

Conclusion:
Our study demonstrates that semaglutide is significantly effective in reducing weight and potentially lowering the risk of heart failure events. This suggests that semaglutide could be a promising therapeutic option for managing obesity-related HfpEF. However, we need large-scale studies to confirm these benefits.
Abstract 4143639: Night Shift Work is Associated With Coronary Microvascular Dysfunction: Involvement of Impaired Fatty Acid Utilization Revealed by Microbial and Metabolic Profiles
Authors: Xia Yan , Che Xinyu , Chen Ao , Chen Zhangwei , Qian Juying , Ge Junbo
Published: November 2024

Background and Aims

Night shift work increases the risk of coronary artery diseases, contributing to worsened prognosis. However, the association between night shifts and coronary microvascular dysfunction (CMD) remains unclear. This study aimed to investigate whether night shift workers have a high incidence of CMD, and the potential mechanisms linking night shifts and CMD.

Methods

We collected cross-sectional clinical traits of traditional cardiovascular risk factors and sleep-related parameters in a security guards cohort at Fudan University. 101 subjects with no history of coronary artery disease were enrolled, of which 50 were night shift workers. Coronary flow reserve (CFR) < 2.0 evaluated by single-photon emission computed tomography (SPECT) myocardial perfusion imaging was recognized as CMD. Integrated analysis of fecal 16s sequencing and serum untargeted-metabolomics was conducted for mechanistic exploration. Microbial features were centered log-ratio(CLR)-transformed for differential enrichment analysis, while metabolic traits were inverse-normal transformed.

Results

After adjusting for age, BMI, remnant cholesterol, TyG (triglyceride-glucose index), NT-pro BNP, and melatonin, night shift work was associated with increased occurrence of CMD (OR 5.26, 95% CI 1.41-28.71; P = 0.012). One year of prolonged night work was 29% more likely to have declined CFR, with an increasing trend between shift durations and CMD (P for trend 0.005). Instead of evident abnormalities in traditional cardiovascular risk factors, night shifts favored a microbial and metabolic profile of perturbed lipid metabolism. Specifically, reduced abundances of probiotic Lactobacillus species and an array of Bacteroides species were the main contributors to the dysbiosis of night-shift gut microbiota. Circulating metabolites of increased 2-Hydroxyhexadecanoylcarnitine and reduced LysoPC(16:0/0:0), a potential feature of impaired palmitic acid utilization, partially mediated the association between night shifts and CMD. Species- and metabolites-based classifiers of CMD status added predicting power combined with night shift durations.

Conclusions

The current study found working night shifts is associated with CMD independent of traditional cardiovascular risk factors. Identifying gut microbiota and circulating metabolites linked to CMD will help to recognize high-risk night shift workers. Probiotics or metabolite supplementation may be promising in conducting a healthier night shift.
Abstract 4143692: Racial Disparities in Age-adjusted Sudden Cardiac Death Rates in the United States: Insights from CDC-WONDER Database, 1999-2020
Authors: Bhatia Hitesh , Rao Adishwar , Khan Muhammad , Agrawal Akriti , Agrawal Siddharth , Parul . , Aafreen Asna , Bhattarai Shraddha , Sharma Saurabh
Published: November 2024

Hypothesis:
Small prospective and dataset-based studies predicted the rates of sudden cardiac death (SCD) are higher in the African American (AA) population as compared to White Americans (WA). However, there is a lack of long-term data over two decades looking

for racial differences in SCD.

Aim:
Our study aims to analyze and quantify the racial differences in age-adjusted mortality rates(AAMR) related to SCDs between AA and WA to further explore potential contributing factors, such as socioeconomic status, sex, and varied comorbidity burdens, to these differences.

Methods:
We analyzed the Centers for Disease Control and Prevention (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) database, containing death certificate records for various causes of mortality in the US from 1999 to 2020. We searched the CDC WONDER database for patients, 18-45 years old whose cause of death was SCD corresponding to ICD-10 code; I46.1. We searched for AAMR and stratified patients based on race and gender on a total population of 48668 (41975 WA; 6693 AA). Temporal trends were analyzed by fitting log-linear regression models using the Joinpoint Regression Program.

Results:
We calculated annual percent change (APC) with 95% confidence intervals (CIs) in AAMR for the line segments linking joint points. The AAMR for SCDs in AA males ranged from 2.1% in 2000 to 0.9% in 2020 with an APC of 0.68 between 1999 and 2009, -26.72 between 2009 and 2012, and 4.34 between 2012 and 2020 suggest that the rate peaked between 2008 and 2010, followed by a significant decline in the following years. WA males had consistently lower rates compared to AA males. The AAMR for WA males peaked at 1.5% in 2000 followed by a stepwise decline until it reached a rate less than 0.9% in 2020, with APCs -1.32 between 1999 and 2009, -19.58 between 2009 and 2012. [Figure A]. AA females had APCs of 2.01, -31.88, and 1.73 while WA females had APCs of -2.32, -21.38, and 0.43 between 1999 and 2009, 2009 and 2012, and 2012 and 2020, respectively [Figure B]. Rates in AA females had a similar progression to that in AA males [Figure C].

Conclusion:
Racial disparities in SCDs related AAMR in the US suggest the role of a complex interplay between healthcare delivery, underlying pathological processes, and race. AA demonstrated higher age-adjusted SCD rates than WA. These findings should be used to guide policymaking and address areas of unmet need in providing racially equitable healthcare for all patients.
Abstract 4143715: An unusual cause for very early dysfunction of a bileaflet mechanical mitral valve (when push comes to shove)
Authors: Khdeir Omar , Kliewer Brian , Vandyck Kofi , Velazco Luis , Sivaram Chittur
Published: November 2024

Description of Case:
A 44-year-old man with a history of mitral valve prolapse and mitral valve repair with triangular resection and partial annuloplasty ring placement eight years prior to presenting with dyspnea and decreased exercise tolerance. His TTE showed severe mitral stenosis with thickening of the posterior mitral leaflet. A redo sternotomy with mitral valve replacement was planned. Intra-procedurally, it was noted that the previous partial annuloplasty ring was impinging on the proximal portion of the posterior leaflet resulting in restricted motion, there was also fusion of the commissures. The partial annuloplasty ring was removed, and a 25 mm On-X mechanical valve was implanted in the mitral position. At the end of surgery, after the patient was off cardiopulmonary bypass, he developed severe hypoxia, and he was started on inhaled nitric oxide. Due to the concern for poor lung compliance, his sternotomy was not closed, and packing was placed in the anterior mediastinum and covered with an antimicrobial incise drape. In the surgical ICU, he became hypotensive and required ionotropic and vasopressor support. After diuresis, the surgical team decided to bring him back to the operating room on postoperative day 3 with concerns for mechanical valve dysfunction with the possibility of redo valve replacement in addition to closure of the anterior mediastinum and sternum. Intraoperative TEE showed that the anterolateral prosthetic mitral valve disc was fixed in the open position. There was no thrombus seen on the leaflets or the valve apparatus. On removal of the anterior mediastinal packing, the valve leaflet started functioning normally. The chest was closed without the need to redo the mechanical mitral valve.

Discussion:
Mechanical valve dysfunction can be either endogenous or exogenous. Our case represents a unique cause of early mechanical mitral valve dysfunction related to external compression by surgical packing impinging on the anterolateral disk inferior to the left atrial appendage from the ventricular side. Intraoperative TEE with 3-D played a vital role in the recognition of this complication and the prevention of redo valve replacement.
Abstract 4143721: Large Sample Size Magnetic Resonance Imaging Measurements to Assess the Relation between Cardiac Function and Structure and White Matter Hyperintensity Volumes.
Authors: Saccoh Adama , Paliwal Nikhil , Sudre Carole , Schmidt Amand Floriaan
Published: November 2024

Background:
People with established cardiovascular disease (CVD) are at risk of early cognitive decline, and neurodegenerative diseases such as dementia. White matter hyperintensities (WMH) of presumed vascular origin are associated with progressive cerebrovascular disease and risk factors for CVD. The shared risk factors include blood pressure, sedentary lifestyle, genomic risk factors like
APOE4
mutations. The extent to which common risk factors explain the co-occurrence of CVD and neurological diseases is unclear.

Purpose:
To determine the extent of which CMR measurements associated with WMH independent of known cerebrovascular risk factors.

Methods:
Cardiac and brain MRI images were analysed for 33,198 UK biobank participants. WMH analysis included 5 brain regions (Frontal, Parietal, Temporal, Occipital, Basal Ganglia and Thalami) and total brain WMH volume. Cardiac traits included stroke volumes, atrial volumes, ejection fractions (EF) of right and left chambers, left ventricular (LV) strain, LV wall thickness and aortic areas
.
Multivariable regression analysis was carried out, where each cardiac trait was regressed on each brain region and adjusted for demographics, cardiac risk factors, family history of disease and socioeconomic factors. Results were evaluated against a multiple testing correct p-value threshold of 0.05, reflecting the number of principle components(n=10) necessary to explain at least 90% of the cardiac trait variability.

Results:
Higher values of 7 cardiac traits (LV end stroke volume, aortic areas, mid and basal wall thickness) associated with higher WMH volumes for all brain regions. Conversely three traits (LV ejection fraction, descending aorta distensibility and RV ejection fraction) associated positively with lower WMH volumes for all brain regions. LV cardiac output and maximum LAV only associated with frontal lobe WMH volumes. Associations on
APOE
- ε4 carriership, a known risk factor of Alzheimer’s disease, showed negative association in homozygous carriers between aortic distensibility of the ascending and descending aorta and higher WMH volumes in the frontal and occipital lobes.

Conclusions:
This study offers insight into WMH burden in a large population of adults. Using cardiac traits as surrogate markers of different cardiac disease could explain how cardiac functionality defines WMH volume distribution and subsequently the wider relationship between cardiovascular and cerebrovascular disease.
Abstract 4143737: Intravascular Ultrasound Guided Versus Coronary Angiography Guided Complex Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Controlled Trials
Authors: Shaikh Yasmeen , Shaikh Tasleem , Moeed Abdul , Yasmin Farah , Goyal Aman , Raza Fatima , alam mahboob
Published: November 2024

Background:
Randomized controlled trials (RCTs) examining the efficacy of intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) when compared with coronary angiography (CA)-guided PCI, for complex coronary artery disease, have produced varied findings. We aim to provide conclusive evidence by pooling all RCTs, including the latest IVUS-ACS trial, on the clinical outcomes of IVUS- and CA-guided complex PCI.

Methods:
MEDLINE, Scopus, and EMBASE were queried from inception till June 2024 for RCTs comparing IVUS and CA in patients undergoing complex PCI for lesions defined as type B2/C according to the American College of Cardiology/American Heart Association guidelines of classification of coronary lesions. The primary outcome was major adverse cardiovascular events (MACE), a composite of cardiac death, myocardial infarction (MI), or ischemia-driven repeat revascularization. Secondary outcomes were cardiac death, MI, probable/definite stent thrombosis (ST), target lesion revascularization (TLR), target vessel revascularization (TVR), and post-procedural minimal lumen diameter (MLD). A random-effects meta-analysis was performed to derive risk ratios (RR) and mean differences (MD) and their corresponding 95% confidence intervals (CI).

Results:
This meta-analysis included 11 RCTs with a total of 9,828 patients (5,037 in IVUS and 4,791 in CA) with a mean age of 63.8 years. IVUS-guided PCI was associated with significantly lower MACE (RR 0.59; 95% CI 0.51–0.68, p<0.00001) than CA. Similarly, patients in the IVUS group were significantly associated with a reduced risk of cardiac death (RR 0.47; 95% CI 0.29–0.73), MI (RR 0.77; 95% CI 0.60–0.99), TLR (RR 0.58; 95% CI 0.45–0.75), and TVR (RR 0.54; 95% CI 0.41–0.71). IVUS was also significantly associated with a greater MLD (MD 0.09; 95% CI 0.05–0.13) when compared with CA. However, no significant association could be ascertained in all-cause death (RR 0.66; 95% CI 0.40–1.10) and ST (RR 0.59; 95% CI 0.34–1.01). All outcomes reported non-significant heterogeneity and no publication bias was evident upon Egger’s regression (p=0.12).

Conclusion:
Patients undergoing complex PCI with IVUS showed significantly lower MACE, cardiac death, MI, TLR, and TVR while having a greater MLD when compared with CA-guided PCI.
Abstract 4143739: Enhancing Care for Patients with ACS in Mexico: Impact of the Get With The Guidelines®-Coronary Artery Disease Mexico Project at the National Institute of Cardiology
Authors: Najera-Rojas Andrea , Robles-Ledesma Mariana , De Los Rios Manuel , Lugo Gavidia Leslie Marisol , Leiva Jose Luis , De los ríos Arce Luis Fernando , Gopar-Nieto Rodrigo , Sierra Lara Martinez Jorge Daniel , González Pacheco Héctor , Arias-Mendoza Alexandra , Araiza Diego
Published: November 2024

Background:
The GWTG initiative has improved global patient care. We introduced GWTG-CAD at Mexico’s largest referral center, the National Institute of Cardiology. This is an independent before/after quality analysis.

Hypothesis:
Implementing a standardized tool will improve ACS patient management and guideline-recommended therapies.

Aims:
To compare the center’s data before/after implementing the GWTG-CAD tool registry.

Methods:
Retrospective, comparative study of ACS patients either transferred from eight referring hospitals or arriving directly to our center. We compared two groups: admissions from July 2022-March 2023 (
before
) and April 2023-April 2024 (
after
). Continuous variables are presented as mean±standard deviation or median and interquartile range, based on their distribution.

Data:
A total of 473 patients, (202 in the
before
-period and 271 in the
after
-period). Age, gender, comorbidities and medical history were non-different between groups. The diagnoses included STEMI 73.2% vs. 58.1%, NSTEMI 23.3% vs. 38.8%, UA 3.4% vs. 2.9%. Symptom onset to first medical contact median time was 504(195-972 min) vs. 395(170-688 min), p=0.28. From the
before
-period, 32.2% underwent pPCI and 61.7% thrombolysis, vs. 46.2% and 42.9% in the
after
-period. Among all patients, the median time of arrival at referring hospital to PCI was 2,329(356-5142 min) during the
before
-period vs. 559(164-1702 min) in the
after
-period (p=0.002). Among STEMI transfers, the time of arrival at referring hospital to PCI was significantly lower (151[110-460] vs. 106[91-142] min, p=0.02). Among direct arrivals, door-to-balloon time was numerically, but not statistically lower (78.5[51-162] vs. 71[45-90] min, p=0.08). Prescription of guideline-recommended therapies from the
before
-period vs.
after
-period was DAPT (93.1% vs. 94.1%, p=0.68), ACEI/ARB (83.7% vs. 85.1%, p=0.68), BB (84.8% vs. 89.8%, p=0.10) and statins (97.3% vs. 95.3%, p=0.26). The overall survival rate was (95.5 vs. 97.4%).

Conclusions:
In this comparative study we observed a significant reduction of transfer to PCI times in all ACS patients after the implementation of the GWTG-CAD project. High prescription of guideline-recommended therapies at discharge were documented.
Abstract 4143740: Efficacy of SGLT2 Inhibitors on Cardiovascular Outcomes Following Acute Myocardial Infarction without Heart Failure: A Propensity-Matched Registry Study
Authors: Issa Rochell , Calcagno Tess , Mahalwar Gauranga , Issa Ryan , Kaelber David , Brateanu Andrei , Menon Venu , Tang Wai Hong , Griffin Brian , Kwon Deborah , Wang Tom Kai Ming
Published: November 2024

Background:
Sodium-glucose co-transporter-2 (SGLT2) inhibitors have a Class 2a indication for treating heart failure with preserved ejection fraction (HFpEF). Despite established benefits in heart failure management, their effects post-acute myocardial infarction (AMI) have not been fully explored.

Aims:
We aim to determine if an SGLT2 inhibitor (SGLT2i) may be associated with improved cardiovascular morbidity and mortality.

Methods:
Patients with AMI treated with or without SGLT2i were identified using the TriNetX global health network, which includes data from over 100 million patients. Propensity score matching utilizing demographic, medical, procedural, medication, and laboratory information created two cohorts of 18,546 patients. Major adverse cardiovascular events (MACE) were defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke. Survival analyses between 30 days and 5 years post-AMI were set to assess cohort outcomes, examining MACE and its individual component outcomes.

Results:
The analysis included 21,032 post-AMI patients between 2014 and 2023, with a mean age of 68.6 ± 11.4 years, 40.5% female. Of the SGLT2i group, 83.2% had T2DM compared to 84.8% of the non-SGLT2i group. The SGLT2i group had significantly lower 30-day mortality (2.6% versus 6.3%, P<0.0001) and MACE (38.0% versus 44.2%, P=0.002). Over a 5-year period, the SGLT2i group exhibited significantly lower mortality (41.3% versus 56.1% HR 0.704, P<0.0001) and a lower rate of MACE (58.6% versus 109.2%, HR 0.860, P<0.0001). Other outcomes, including MI, stroke, and bleeding events, also favored the SGLT2i group at both 30 days and 5 years (P<0.0001).

Conclusions:
This study showed that the use of SGLT2i post-AMI in patients with normal EF was associated with decreased mortality, MACE, AMI, and stroke. These results advocate for the further investigation of SGLT2i in the post-AMI care path, highlighting their potential to improve post-AMI outcomes.
Abstract 4143744: Cross-talk between oxidized LDL, oxidative stress and renin-angiotensin-aldosterone system: Impact on endothelial function and atherosclerosis
Authors: Catar Rusan , Kamhieh-Milz Julian , Goettsch Claudia , Chen Lei , Zickler Daniel , Taye Ashraf , Hofmann Anja , Brunssen Coy , Muller Gregor , Cybularz Maria , Hengst Clara , Villar Ballesteros Maria de Leyre , Lehmann Susann , Schubert Undine , Ludwig Barbara , Ziegler Christian , Bornstein Stefan , Krug Alexander , Walther Thomas , Moll Guido , Morawietz Henning
Published: November 2024

Introduction/Background:
Hypertension and hypercholesterolemia are important risk factors of endothelial dysfunction and atherosclerosis. Previous studies suggested a crosstalk between an activated renin-angiotensin-aldosterone system (RAAS), reactive oxygen species (ROS) and oxidized low-density lipoproteins (oxLDL) in atherosclerosis, but the underlying molecular mechanisms are not well understood.

Research Question/Hypothesis:
Can we identify novel signaling pathways controlling the molecular crosstalk of the RAAS with ROS and oxLDL in endothelial dysfunction and atherosclerosis?

Methods/Approach:
The impact of AT
1
R blockade on oxLDL-induced superoxide anion formation and endothelial dysfunction was studied in human umbilical artery endothelial cells and aortic rings of wild-type mice by chemiluminescence and Mulvany myograph. We cloned 5’-terminal deletions of the AT
1
R promoter and assessed the luciferase activity in human endothelial cells. Oct-1 binding to the human AT
1
R promoter region was studied by EMSA. Further assays included real-time PCR, confocal microscopy, Western blotting, G protein reporter assays, phospho-ERK1/2 antibodies and specific siRNAs. The data were validated in heart of obese C57BL/6 mice and cardiac and aortic tissue of AT
1a
/AT
1b
double knockout mice
in vivo
.

Results/Data:
AT
1
R promoter activation studies upon Ang II- and oxLDL-stimulation in endothelial cells revealed that Ang II and oxLDL activate AT
1
R signaling through G protein Gα
12/13
, followed by activation of ERK1/2 MAP kinases, and transcription and translation of Oct-1, resulting in up-regulation of AT
1
R, LOX-1 and NOX2 expression, which could be antagonized by specific inhibitors at each step of the identified signaling cascade. AT
1
R blockade improved oxLDL-induced endothelial dysfunction in aortic rings of wild-type mice. Male C57BL/6 mice fed a high-fat diet exhibited upregulation of Oct-1 levels in cardiac tissues, compared to normal controls, while AT
1a
/AT
1b
double knockout mice demonstrated downregulation of Oct-1, AT
1
R, LOX-1, and NOX2 on mRNA and protein level in cardiac and aorta tissue, thus confirming the identified signaling cascade
in vivo
.

Conclusions:
Oct-1 is an essential transcription factor for Ang II- and oxLDL-induced upregulation of AT
1
R and LOX-1 expression in endothelium, thus identifying a novel molecular cross-talk of oxLDL with ROS signaling and the RAAS contributing to development of endothelial dysfunction and atherosclerosis.
Abstract 4143776: Growth Differentiation Factor 15 is a Novel Cardiac Hormone that Causes Cachexia in Heart Failure
Authors: Trujillo Maya , Gupta Ria , Lee Da Young , Jiao Zhe , Berhanu Samuel , Antolic Andrew , Weitzmann M. Neale , Burke Michael
Published: November 2024

Background:
Cachexia is a common complication of heart failure (HF) and is associated with high mortality. Growth differentiation factor 15 (GDF15) regulates food intake and can cause cancer cachexia. GDF15 is a sensitive biomarker in humans, though its biologic function in HF is unknown.

Objective:
We sought to define the role of GDF15 in HF.

Methods:
We utilized a genetic mouse model of dilated cardiomyopathy (DCM) caused by a mutation in the phospholamban gene (PLN
R9C
). PLN
R9C
mice have dysregulated cardiac calcium handling (a common feature of nearly all forms of HF) and develop progressive DCM that leads to HF and premature death. Expression analyses were performed on tissue and isolated myocardial cells via flow cytometry and single nucleus RNA-sequencing (snRNA-seq) in PLN
R9C
and age-matched wild type (WT) mice. A double transgenic mouse was created by crossing PLN
R9C
with a constitutive
Gdf15
knock-out (KO). Cardiac function and fibrosis were assessed using echocardiography and histochemistry, respectively. We measured food intake in individually housed mice, and tissue composition was quantified by weight at necropsy, dual-energy X-ray absorptiometry (DXA) and histochemistry. Survival was assessed by Kaplan-Meier.

Results:
GDF15 mRNA (43-fold; p<0.01) and protein (54-fold; p<0.01) were increased in LV tissue, and circulating GDF15 was elevated (8.3-fold; p=0.03) in PLN
R9C
mice. In other organs,
Gdf15
expression was minimal and did not increase with DCM. Single nucleus sequencing revealed that
Gdf15
was specifically increased in cardiomyocytes with progression to DCM. The GDF15-specific receptor GDNF-family receptor a-like (GFRAL) was selectively expressed in the hindbrain of these mice. PLN
R9C
mice consumed less food and developed cachexia (reduced fat and lean mass at necropsy, reduced fat mass by DXA and reduced skeletal muscle cross-sectional area; p<0.01 for all vs. WT), findings that were reversed in PLN
R9C
-
Gdf15
KO mice.
Gdf15
KO had no effect on cardiac structure or function by echocardiography and PLN
R9C
/
Gdf15
KO mice displayed only a small reduction in cardiac fibrosis relative to PLN
R9C
mice (-3%; p<0.01). Despite this,
Gdf15
KO prolonged survival in PLN
R9C
(29±3 vs. 25±3 weeks; p<0.01).

Conclusions:
Selective upregulation of GDF15 in failing cardiomyocytes triggers cardiac cachexia and worsens survival by an extra-cardiac mechanism. We therefore propose that GDF15 is a novel cardiac hormone produced in HF.
Abstract 4143788: Physical Activity Reduces Incident DVT Risk: Greater Impact Among Individuals with Anxiety or Depression
Authors: Civieri Giovanni , Lau Hui Chong , Abohashem Shady , ABI KARAM KRYSTEL , Aldosoky Wesam , Khalil Maria , Seligowski Antonia , Osborne Michael , Rosovsky Rachel , Tawakol Ahmed
Published: November 2024

Background:
Physical activity (PA) reduces cardiovascular (CV) disease risk, and this has recently been shown to be due, in part, to reduction of stress-related neural activity (SNA). Further, the CV benefits of PA are higher in individuals likely to have higher baseline SNA (i.e., those with depression/anxiety). Moreover, anxiety and depression associate with increased risk of deep venous thrombosis (DVT) partly through increased SNA, yet it remains unknown how PA impacts this relationship.

Hypotheses:
1) PA associates with lower risk of DVT, 2) this PA benefit is more pronounced in individuals with anxiety and depression.

Aims:
To evaluate the association between PA and DVT risk and the differential benefits among subjects with anxiety or depression.

Methods:
Subjects enrolled in the Mass General Brigham Biobank were studied; total PA was derived from a health survey that assessed different activities during the previous year. Higher
vs
lower PA was defined according to quintiles of PA in our population (low PA: 1° and 2° quintile; high PA: 4° and 5° quintile; subjects in the 3° quintile were excluded to avoid possible overlaps). Depression, anxiety, and DVT were defined using ICD codes. Subjects <18 years old or with previous DVT were excluded. Risk of incident DVT was investigated with multivariable Cox-regression.

Results:
49,081 subjects (mean age 53.8 ± 16.6 yrs, 39.8% male) were studied. The incidence of DVT progressively decreased across quintiles of PA (2.1% vs 1.9% vs 1.7% vs 1.3% vs 1.2%; p<0.001). High PA was associated with lower risk of incident DVT after adjustment for the most common DVT risk factors (age, sex, cancer, oral contraceptives, and obesity; HR 0.764 [95% CI 0.648-0.901, p=0.001]) and additional confounders (
Fig. 1A
). The beneficial effect of PA on DVT risk was higher in those with anxiety and depression (interaction with anxiety p=0.002; interaction with depression p=0.052;
Fig. 1B
).

Conclusion:
PA associates with lower risk of DVT, and this association is more pronounced among individuals with anxiety or depression. These results provide further support for a brain-clot connection and suggest that further mechanistic studies are needed.
Abstract 4143799: Dose-Dependent Inhibition of Lp(a) Oxidation by Eicosapentaenoic Acid (EPA) Compared to a Fibrate and Statin due to Lipid Interactions and Antioxidant Properties
Authors: Sherratt Samuel , Libby Peter , Bhatt Deepak , Mason Preston
Published: November 2024

Background:
Elevated Lp(a) levels are an independent and causal risk factor for cardiovascular (CV) disease. Levels of oxidized Lp(a) were more predictive of CV events and endothelial dysfunction than non-oxidized forms in patients. The omega-3 fatty acid EPA reduced CV events in high-risk patients, including those with elevated Lp(a) (REDUCE-IT). EPA inhibits lipid oxidation due to scavenging activity and lipophilicity. We compared the effects of a pharmacologic concentration of EPA on oxidation rates for Lp(a) versus LDL compared to a fibrate and statin, along with lipid affinity.

Methods:
Lp(a) was enriched to 66% of total ApoB-containing particles from patients with elevated levels by isopycnic centrifugation. Samples of Lp(a) and LDL (50 µg/ml) were incubated at 37°C for 30 min with EPA at various concentrations (10 – 100 µM) compared to equimolar fenofibric acid or rosuvastatin (10 µM). Samples then underwent copper sulfate-induced oxidation (20 µM) monitored by formation of malondialdehyde (MDA). Lipid affinity of each agent was measured by UV/Vis spectroscopy using lipid vesicles containing phosphatidylcholine and cholesterol at a 0.3:1 ratio. Drug concentrations in vesicles versus buffer were measured and compared to standard curves.

Results:
Lp(a) enriched ApoB particles underwent time-dependent oxidation by 51-fold, peaking after 2 h (4.13 ± 0.10, p<0.001). EPA significantly inhibited Lp(a) oxidation in a dose and time-dependent manner; after 2 h, EPA inhibited oxidation from 31 to 69% (
p
<0.001) at 5 concentrations while fenofibric acid and rosuvastatin lacked antioxidant activity. Similar distinct antioxidant effects of EPA were observed in non-modified LDL. The antioxidant activity EPA correlated with higher lipid affinity that was significantly greater than fenofibric acid and rosuvastatin (
p
<0.001).

Conclusions:
EPA inhibited oxidation of Lp(a) enriched plasma in a dose-dependent fashion due to potent scavenging mechanism and high lipid affinity. The fibrate or statin tested did not exert similar antioxidant effects. The potent antioxidant actions of EPA may contribute to reduced events in REDUCE-IT, including in subjects with elevated Lp(a).
Abstract 4143814: Utility of Echocardiography to Prognosticate Fetal High Cardiac Output States
Authors: Viveiros Anissa , Hornberger Lisa , McBrien Angela , Eckersley Luke
Published: November 2024

Background:
Fetal anemia can lead to high cardiac output (CO) failure, fetal hydrops and fetal demise. Intrauterine transfusion (IUT) is the standard of care, but carries risks of premature delivery and fetal death; therefore, it is critical to identify the most affected fetuses prior to intervention. Elevation of the peak systolic velocity in the middle cerebral artery (MCA-PSV) is routinely used to indicate intervention; however, the reported false positive rate is as high as 12 to 14%.

Aim:
Assess whether measured CO by fetal echocardiography (FE) can be used as a complementary screening tool to predict fetal anemia.

Methods:
We identified all pregnancies referred for FE from 2009-2023 with suspected fetal anemia (n=49). We reviewed FEs (n=88) to measure ventricular function, combined CO (aortic and pulmonary outflows), and measured ventricular dimensions. Percentiles for CO were used based on published normative data. The MCA-PSV was measured and reported as multiples of the median (MoM). Where available, pre-transfusion fetal hemoglobin (Hb) readings were reported as a MoM, with temporally matched FE studies performed prior to IUT included for analysis (n=8).

Results:
Overall
,
MCA-PSV was positively associated with left ventricular (LV) CO, but not with right ventricular (RV) or combined (CCO) (LV CO p=0.037, Figure 1A; RV CO p=0.790; CCO p=0.290). The LV CO correlated with z-scores for LV and RV end diastolic dimensions (EDD) (LVEDD p<0.001; RVEDD p=0.018). The RV CO and CCO also were positively associated with LVEDD (p=0.004 and p<0.001, respectively), and RVEDD (p=0.009 and p=0.003, respectively). However, the MCA-PSV did not correlate with ventricular dimensions (LVEDD p=0.524 and RVEDD p=0.689). Fetal Hb was negatively correlated with the MCA-PSV, which approached statistical significance (Figure 1B). Fetal Hb negatively correlated with the LV CO (Figure 1C), but not with RV CO or CCO (Figure 1D).

Conclusion:
Preliminary results suggest that fetal LV CO may confer additive value to current MCA-PSV measurement in predicting the severity of fetal anemia. Larger studies are warranted to explore the relationship of fetal LV CO and MCA-PSV with fetal Hb and prognosis in high output cardiac failure.