bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4146676: Trends In Temperature Control After Cardiac Arrest In Cardiac Intensive Care Units: An Analysis From The Critical Care Cardiology Trials Network (CCCTN) Registry
Authors: Ariss Robert , Guo Jianping , Morrow David , Berg David
Published: November 2024

Introduction:
Temperature control (TC) is recommended for comatose patients after cardiac arrest (CA). In the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial, targeted normothermia (≤37.5°C) resulted in similar mortality and functional outcomes as targeted hypothermia (33°C).

Aim:
To examine temporal trends in TC use and targets in CICUs before and after the TTM2 trial.

Methods:
The Critical Care Cardiology Trials Network (CCCTN) is a multinational registry of advanced CICUs coordinated by the TIMI Study Group (Boston, MA). Consecutive admissions were captured during annual 2-month collection periods across participating CICUs (2018-2023). Comatose CA patients were classified as being admitted before (2018-2021) or after (2021-2023) publication of TTM2. TC utilization rates, and temperature targets were compared between the pre- and post-TTM2 eras, including in subgroups of shockable (VT/VF) and non-shockable (PEA/asystole) rhythms.

Results:
Of 1,355 comatose CA admissions (median age 64y, 30% women, 69% OHCA, 52% shockable/40% non-shockable/8% unknown, 70% in shock, 28% acute MI), 773 were pre-TTM2 and 582 were post-TTM2. Rates of TC use were similar pre- and post-TTM2 (74% vs. 75%; p=0.45), including in the subgroups of shockable (84% vs 82%; p=0.45) and non-shockable rhythms (64% vs. 67%; p=0.53). As compared to pre-TTM2 admissions, post-TTM2 admissions had significantly higher median target temperatures (38% [pre] vs 67% [post] with target temperature ≥36°C; p < 0.001; Figure 1A). This trend was consistent in the subgroups of shockable and non-shockable rhythms (Figure 1B).

Conclusion:
In a large CICU cohort of comatose CA patients, overall TC utilization remained stable, but temperature targets were higher after publication of the TTM2 trial. These data provide reassurance that temperature control remains a focus of post-arrest care despite a shift in clinical practice patterns favoring normothermia.
Abstract 4146702: Analysing the Global Landscape of Hypertension-Related Aortic Aneurysm Mortality: Insights from 31-Year Analysis of Global Burden Of Disease 2021
Authors: Shaukat Muhammad Talha , Rehman Wania , Mohsin Aleenah , Rehman Aqeeb Ur , Rahman Saad Ur , Qureshi Muhammad Ahmad , Mohsin Ali
Published: November 2024

Background:
Aortic aneurysm, a potentially life-threatening condition characterized by weakness of the aortic wall, poses a significant health risk, especially when concurrent with high systolic blood pressure. In an aging population experiencing the effects of smoking and atherosclerotic disease, it is imperative to explore the burden associated with hypertension-related aortic aneurysm mortality.

Methods:
The Global Burden of Diseases (GBD) study was used to extract data for high systolic blood pressure-related aortic aneurysm from 1990-2021. Dataset was stratified globally, continent wise, and by World Bank income levels. Age-standardized death rates (ASDRs), disability-adjusted life years (DALYs), and years of life lost (YLL) were examined. Jointpoint regression was used to quantify these estimates and calculate average annual percentage changes (AAPCs).

Results:
Globally, the age standardized death rates (ASDR) for hypertension-related aortic aneurysm rupture had a declining trend from 1990-2021. In 1990, the ASDR was 0.52 (95% UI 0.39-0.65), which declined to 0.32 in 2021 (AAPC=-1.53; 95% CI -1.57 to -1.48). The disability-adjusted life-years (DALYs) were 9.55 in 1990 and decreased to 6.19 in 2021 (AAPC=-1.38; 95% CI -1.42 to -1.33). The age standardized years of life lost (YLL) also showed a uniform drop over the same period (AAPC=-1.38; 95% CI -1.42 to -1.33). In continent wise analysis, North America and Europe exhibited significant decline [(AAPC=-2.44; 95% CI -2.48 to -2.40) and (AAPC=-1.58; 95% CI -1.64 to -1.51) respectively], while Africa showed minimal variation. Importantly, however, Asia was the only continent with a rising mortality during this period (AAPC=0.77; 95% CI 0.73-0.81). According to World Bank income levels, high income countries had continuous decline in death rates while lower-middle income countries had increasing deaths rates. Upper-middle and low-income countries both had minimal variation in death rates during this period.

Conclusion:
Global efforts to reduce hypertension-related aortic aneurysm mortality have yielded positive results, but regional disparities persist. Continued research, prevention, and healthcare interventions are crucial to further mitigate this health risk.
Abstract 4146722: Incidence and Risk Factors for Atrial Arrhythmia in Adults with Systemic Right Ventricle
Authors: Havangi Prakash Shisheer , Ahmad Rimsha , Chiriac Anca , Connolly Heidi , Egbe Alexander , Deshmukh Abhishek , Asirvatham Samuel , Vijayakumar Keerthika , Madhavan Malini
Published: November 2024

Introduction:
The incidence and risk factors for atrial arrhythmia (AA) [atrial fibrillation (AF) and atrial flutter (AFL)] in adults with systemic right ventricle (SRV), specifically congenitally corrected-TGA (cc-TGA) and D-TGA palliated with atrial switch procedures, is not well understood. This study aims to better define these risks.

Methods:
Adults with SRV presenting to the Mayo Clinic between 1971 and 2022 were identified. Clinical characteristics, ECG and echocardiographic parameters were recorded at first evaluation. Sustained AA (> 30s) incidence at follow-up was documented using ECG. Cox regression analysis identified associations of incident AA.

Results:
Among 447 patients with SRV (mean age 34.7±14.8, 55.9% male, cc-TGA n=247; D-TGA post-atrial baffle n=200), AA was documented in 231 (51.6%) at a mean age of 37.5±18.8y. Isolated AF was observed in 88 (38.1%), isolated AFL in 71 (30.7%), and both AF and AFL in 72 (31.2%) patients. Univariate analysis showed significant predictors of AA as: age (HR:1.03, p<0.001), male sex (HR:1.49, p=0.026), NYHA class≥2 (HR:1.98, p<0.001), ventricular pacing (HR:1.64, p=0.019), QRS duration (HR:1.008, p<0.001), SRV enlargement (HR:1.73, p=0.01), SRV ejection fraction (HR:0.979,p=0.012), left atrial enlargement (HR:1.947, p=0.006), hypertension (HR:1.57, p=0.047), CKD (HR:0.991, p=0.021), and obesity (HR:1.66, p=0.023). In multivariable analysis, age (HR:1.032, p<0.001) and QRS duration (HR:1.007, p=0.013) were significant predictors of AA. Kaplan Meier analysis of time from first evaluation to incidence of AA is shown in the figure. AA was associated with heart failure in 56 (26.7%) patients. During 11.2±10.5 years of follow-up, mortality occurred in 50 (21.6%) with AA and 19 (8.8%) without AA.

Conclusion:
Atrial arrhythmia occurred in more than half of patients with SRV, predominantly in the third decade of life. Significant associations of AA included advancing age, longer QRS duration, enlargement of pulmonary venous atrium, reduced SRV function, hypertension and obesity. AA was associated with heart failure in one-fourth of patients and higher mortality. Close monitoring and early intervention in patients with risk factors may help mitigate the development of AA.
Abstract 4146739: HBA1C Level Affects Stroke Outcome in AF Patients
Authors: Bsoul Mayana , Assaf Ala' , bidaoui ghassan , Tirado Polo Francisco , Gu Yuxuan , Mekhael Mario , Younes Hadi , Jia Yishi , Liu Yingshuo , Feng Han , Lim Chanho , Hui Yanpei , Hassan Abboud , Rao Swati , Kreidieh Omar , Pandey Amitabh , donnellan eoin , Marrouche Nassir
Published: November 2024

Background:
The CHA2DS2-VASc score quantifies stroke risk for atrial fibrillation (AF patients), but considers one point for diabetic patients, regardless of glycemic control.

Objective:
We aim to study the impact of the level of HBA1C on the stroke risk in AF patients.

Methods:
Utilizing data from the Research Action for Health Network (REACHnet) database, we studied patients within the Tulane University health system from 2010 to 2019. We only included patients diagnosed with AF with at least one HbA1c measurement. For each patient, the average HbA1c was used if there were multiple HbA1c measurements. Patients were categorized to 2 groups; group 1 is patients with HbA1c ≥7% but <9%, while group 2 is Hba1c level more than ≥9%, which is severe hyperglycemia. Patients were followed up for 5 years from the diagnosis of AF. Cox regression was used to investigate the correlation between HBA1C level and ischemic strokes, with potential confounders corrected using the model.

Results:
We included 1120 patients, there was no significant difference in age (65± 10 vs 64 ± 11, p= 0.308), gender (39.1% vs 33% females, p= 0.287), BMI (30.85 ±8.9 vs 30.74 ±7.9, p=0.672) or race (35.6% vs 36.0% African Americans, p=1.000) between the 2 groups. Group 1 included 87 (7.8%) patients, while group 2 included 1033 (92.2%) with severe hyperglycemia. There was no significant difference between anticoagulants between the 2 groups (74.7% vs 71.4%, p=0.620). Our analysis showed that patients with severe hyperglycemia are at a significantly higher stroke risk compared to those with lower levels (p = 0.027, [HR] = 2.146, CI= [1.09-4.224]), correcting for age, sex, race, CHA2DS2-VASc score, anticoagulants, CAD, hyperlipidemia, and CKD. (Table.1)

Conclusion:
The analysis showed that severe hyperglycemia doubles the risk of stroke among AF patients. The findings of our study suggest that the severity of hyperglycemia may be more important than the binary status of diabetes. This study further underscores the importance of glycemic control of HBA1C in reducing thromboembolic events.
Abstract 4146753: Digital Health Interventions After An Acute Coronary Syndrome: A Systematic Review And Meta-analysis Of Randomized Controlled Trials
Authors: Kritya Mangesh , Lingamsetty Shanmukh sai pavan , Maurya Priyanshi , Doma Mohamed , Hernandez Pastrana Sarai , Fatima Syeda Rubab , Huang Wilbert , Naji Zahra , Hamdanieh Maya , Martignoni Felipe
Published: November 2024

Background:
The role of digital health interventions (DHI) in addition to usual care (UC) in patients discharged after an acute coronary syndrome (ACS) remains uncertain.

Hypothesis:
DHI improves medication adherence, and systolic blood pressure (BP) control and reduces mortality in patients after an ACS.

Purpose:
To ascertain the efficacy of adding DHI to UC in patients discharged after an ACS through a systematic review and meta-analysis.

Methods:
We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) comparing DHI plus UC versus UC alone in patients discharged after an ACS. We pooled risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for binary and continuous outcomes, respectively. Our outcomes of interest were medication adherence (as per the studies' definitions), all-cause mortality, and systolic BP. Statistical analyses were performed using R software version 4.4.0.

Results:
We included 22 RCTs comprising 20,587 patients, of whom 14,079 (68.4%) were randomized to DHI + UC. The mean age was 59.5 years and 58.5% were male. About 15% had diabetes mellitus at baseline while 54% had hypertension. In the pooled analysis, DHI plus UC significantly increased medication adherence (RR 1.06; 95% CI 1.01 to 1.13; p=0.03; Fig. 1) and reduced systolic BP (MD -3.16 mmHg; 95% CI -5.53 to -0.79; p<0.01; Figure 2A) compared with UC alone. There was no significant difference between groups in terms of all-cause mortality (RR 0.87; 95% CI 0.52 to 1.44; p=0.58; Figure 2B).

Conclusion:
In this meta-analysis of RCTs among patients discharged after an ACS, UC with DHI significantly improved medication adherence and lowered systolic BP relative to UC alone, without significantly affecting mortality.
Abstract 4146787: Causal Association between Major Depressive Disorder and Cardiovascular Diseases: A Meta-Analysis of Mendelian Randomization Studies
Authors: Kothawala Azra , Bollu Bhaswanth , Shafi Nimra , Sharma Akshay , Yalla Naga Amrutha Sai , Singh Sandeep , Desai Rupak
Published: November 2024

Background:
Major depressive disorder (MDD) has been hypothesized to have a causal relationship with various cardiovascular diseases, including coronary artery disease (CAD), atrial fibrillation (AF), and heart failure (HF). Our meta-analysis of Mendelian Randomization (MR) studies aims to identify these associations by using genetic variants as instrumental variables and minimizing confounding factors and reverse causation.

Methods:
We systematically reviewed the Pubmed, Embase, and Scopus databases to find studies through May 2024 evaluating the association of MDD with the occurrence of Coronary Artery Disease (CAD), Heart Failure (HF), and Atrial Fibrillation (AF). Data sources included multiple genome-wide association studies (GWAS) involving European and mixed ancestries, the IEU Open GWAS Project, the Psychiatric Genomics Consortium (PGC), and combined data from 23andMe, PGC, and the UK Biobank. Random effects models and I
2
statistics were used for pooled odds ratios (OR) and heterogeneity assessments, respectively. The impact of individual studies on the overall estimate was assessed with Leave one-out sensitivity analysis.

Results:
MDD and CAD: Seven studies were included in the analysis. The overall Inverse Variance Weighted (IVW) estimate indicated odds of developing CAD were 17% higher in those with MDD than without (OR: 1.17, 95% CI: 1.08-1.28, P < 0.01), with substantial heterogeneity (I
2
= 89.89%, P < 0.01). Leave-one-out analysis confirmed equal results as the pooled estimate remained significant across all iterations (OR range: 1.14 to 1.20).

MDD and AF:
Three studies were included in the analysis. No significant association between MDD and AF was observed in the pooled IVW estimate (OR: 1.03, 95% CI: 0.98-1.08, P = 0.35). The heterogeneity was low (I
2
= 5.22%, P = 0.35).

MDD and HF:
Three studies were included in this analysis. MDD was associated with a significant risk of developing heart failure (OR: 1.11, 95% CI: 1.05-1.18, P < 0.01), with no observed heterogeneity (I
2
= 0%, P = 0.49).

Conclusion:
MDD increases the risk of CAD by 17% and the risk of HF by 11% with no significant association between MDD and AF. The substantial heterogeneity in the MDD-CAD association suggests that further studies are warranted to explore potential sources of this variability. These findings highlight the importance of managing depressive symptoms as part of cardiovascular disease prevention strategies.
Abstract 4146790: Circadian Variation of ST Elevation Mycardial Infarction is Associated Not Only With Chest Pain Onset But Also Infarct Related Artery and TIme Delays to Treatment.
Authors: Siudak Zbigniew , Tkaczyk Filip , Pytlak Kamil , Natalia Dardzinska , Jaskulska Paulina , Zabojszcz Michal
Published: November 2024

Introduction:
Available data suggest there is some regularity in the time of the day when patients experience their first clinical symptoms (pain) of ST Elevation Myocardial Infarction (STEMI). It has been noticed that the largest number of cases of myocardial infarction are observed in the early morning. Some studies, especially in Asian populations, have found a shift into the afternoon hours. Additionally, some publications suggest the existence of secondary peaks of incidence in the evening hours. There also seems to be a relationship between night hours and the occurrence of myocardial infarctions in patients with sleep apnea. Although the risk of myocardial infarction is highest in the morning, there are differences depending on the region and population which might indicate the influence of local and individual factors on the circadian rhythm of the disease.

Objective:
To analyze circadian variation of STEMI first chest pain onset occurence on one of the largest populations tested so far and to see if there is an association with time delays to Percutaneous Coronary Intervention (PCI).

Methods:
Data from the Polish National PCI Registry (ORPKI Registry) on patients with confirmed STEMI diagnosis who underwent either coronary angiography and/or PCI from 2014 untill 2022 were analyzed.

Results:
There were 153 543 individual patients in the analyzed time period with 68% of males. Circadian variation in the probablity of STEMI occurence in both men and women is presented in Figure 1 (p>0.05). Median time from chest pain onset to first medical contact (FMC) was 180 minutes (60-260; 95% CI) at 3 am and 90 minutes (59-196; 95% CI) at 1 pm respectively (p<0.001). Median tIme from FMC to PCI was 77 minutes (53-120; 95%CI) at 1 pm vs 87 minutes (60-140; 95% CI) at 7 am. Likewise the total time of ischemia from chest pain onset to PCI has been similiary affected. No differences in the periprocedural mortality was found. We have found no influence of diabetes, age and presence of chronic pulmonary obstructive disease on the circadian pattern. Interestingly, we have seen a circadian variation of LAD vs RCA ratio with LAD nadir at noon hours and peak during midnight and RCA the opposite (p<0.001).

Conclusiions:
Strong circadian variation exists in the probablity of occurence of STEMI in both males and females with peak incidence at 8 am. STEMI chest pain onset time had influence on time delays to PCI. A circadian variaiton in LAD/RCA occlusion was observed.
Abstract 4146818: Interplay of Coronary Artery Calcium and Predicting Risk of cardiovascular disease EVENTs Equations in ASCVD Risk Prediction
Authors: Acquah Isaac , Hagan Kobina , Javed Zulqarnain , Shahid Izza , Nasir Khurram , Al-Kindi Sadeer
Published: November 2024

Background:
The American Heart Association recently introduced the Predicting Risk of CVD EVENTs (PREVENT) equations, which incorporate additional cardiometabolic risk factors to estimate atherosclerotic cardiovascular disease (ASCVD) risk in younger adults in a race-neutral manner. This study aims to assess the interplay of estimated ASCVD risk by PREVENT equations and coronary artery calcium (CAC) and their association with hard ASCVD events in a large population-based cohort.

Methods:
We analyzed data from 6,380 individuals aged 45-79 years and free of ASCVD at baseline from the Multi-Ethnic Study of Atherosclerosis (obtained from the Biologic Specimen and Data Repository Information Coordinating Center [BioLINCC]). Participants were classified by baseline CAC score (0, 1–100, >100) and clinically relevant PREVENT categories (<5%, 5%–<7.5%, ≥7.5%). In unadjusted survival analysis, we evaluated the incidence and risk of hard CVD events across PREVENT and CAC scoring profiles.

Results:
Among individuals with <5% risk, 70% had CAC=0 and 8% had CAC>100, whereas among individuals with ≥7.5% risk, 27% and 42% had CAC=0 and CAC>100 respectively, as shown in figure (
panel A
). Overall, 609 hard CVD events occurred in a median follow-up of 14.1 years (10-year observed rate of 14.3%). Individuals with <5% PREVENT score and CAC >100 had an event rate 1.5 times higher than individuals with ≥7.5% risk and CAC 0 (8.9% vs 5.9%). A CAC score of 0 was associated with 10-year CVD event rates of less than 7.5% across the estimated ASCVD risk categories (
Figure, panel B
). The interplay between continuous CAC and PREVENT is shown in figure (
panel C
)

Conclusion:
Across the spectrum of PREVENT-based ASCVD risk, the distribution of CAC is heterogeneous. A high CAC burden, even among individuals with a low estimated 10-year risk by PREVENT, is associated with an elevated event rate. Conversely, the absence of CAC, even among those with elevated risk, is associated with a low event rate. CAC testing can support individual preferences in the context of shared decision making when estimating ASCVD risk and subsequent management choices.
Abstract 4146823: Trends and Outcomes in Heart Failure Admissions and Cardiogenic Shock Among Patients with Congenital Heart Disease
Authors: Alhuneafat Laith , Ghanem Fares , Alexy Tamas
Published: November 2024

Introduction:
This study examines trends in heart failure admissions, cardiogenic shock, mechanical circulatory support (MCS) usage, and cardiac transplant among patients with congenital heart disease (CHD), focusing on double (DV) and single ventricle (SV) CHD.

Methods:
We analyzed the national inpatient sample from 2016 to 2020 for heart failure admissions, including double and single ventricle CHD, and trends in cardiogenic shock, MCS utilization, cardiac transplants, and mortality.

Results:
Out of 4,963,884 total admissions, 29,805 were for DV-CHD and 2,415 for SV-CHD. Patients without CHD were older (mean age 71.5 years) than those with DV-CHD (mean age 59.8 years) and SV-CHD (mean age 17.9 years). Non-CHD patients had shorter stays (mean 5.8 days), and lower total charges. CHD admissions remained stable from 2016 to 2020. Cardiogenic shock rates were highest among SV-CHD patients, with significant fluctuations, followed by DV-CHD patients. MCS usage increased, particularly among SV-CHD patients, while DV-CHD patients showed an upward trend and patients without CHD had consistently lower usage. Heart transplant rates were low but increased slightly in 2020 for patients without CHD, with DV and SV CHD patients showing fluctuating rates peaking in 2018 and 2019, then declining in 2020. Inpatient mortality rates were highest among SV-CHD patients, followed by DV-CHD patients, both experiencing significant fluctuations and a general increasing trend, while patients without CHD had the lowest and most stable rates.

Conclusion:
Our analysis highlights trends in CHD management, including age, length of stay, mortality rates, and healthcare costs. Variations in cardiogenic shock, MCS usage, and cardiac transplants emphasize the need for adaptive clinical practices to optimize patient outcomes.
Abstract 4146824: Performance of Clinician-Assigned SCAI Shock Staging in the AHA Cardiogenic Shock Registry
Authors: Berg David , Bohula Erin , Patel Siddharth , Palazzolo Michael , Krucoff Mitchell , Morrow David
Published: November 2024

Background:
SCAI staging of cardiogenic shock (CS) severity facilitates communication about the presentation and trajectory of CS. Most prior validations of SCAI staging have used registry-specific algorithmic adaptations of the staging criteria. Few studies have evaluated clinician-assigned SCAI staging based on holistic assessment of all clinical data.

Aim:
To assess the ability of initial and serial clinician-assigned SCAI staging to stratify risk of in-hospital mortality in a large, broadly representative CS population from the AHA CS Registry.

Methods:
Consecutive CS admissions enrolled in the Registry (64 sites, 2022-2024) were included. Clinician-assigned SCAI stage was captured at CS onset (first 6h) and serially (6-12h after CS onset). Cases with available SCAI stage at both timepoints were classified as having improved, unchanged, or worsened SCAI stage. Associations of in-hospital mortality with initial and early change in SCAI stage were assessed using logistic regression; for the latter, models were adjusted for initial SCAI stage. Key subgroups defined by CS etiology (AMI-CS vs. HF-CS) and preceding cardiac arrest (CA) were examined.

Results:
Among 4,311 CS admissions, 3,110 (72%) had initial SCAI stage assessments (median age 66y, 33% women, 30% AMI-CS, 50% HF-CS, 21% preceding CA) and 2,867 (67%) had serial assessments. Most CS was initially staged as SCAI C (B: 12%; C: 59%; D: 19%; E: 10%), with a higher proportion of SCAI D/E in those with AMI-CS (34%) or preceding CA (60%). There was a stepwise gradient of mortality across SCAI stages (p<0.001;
Fig-A
), consistent when stratifying by CS etiology and preceding CA (p<0.001 for each;
Fig-B/C
). In the 12h after CS onset, most SCAI staging was unchanged (73%; worsening: 15%; improving: 12%); however, SCAI staging was more dynamic in those with preceding CA. Early worsening or improvement in SCAI stage was associated with higher (aOR 3.7, 95% CI 2.9-4.6) and lower (aOR 0.4, 95% CI 0.3-0.5) odds of mortality, respectively (
Fig-D
).

Conclusion:
In this initial analysis from the AHA CS Registry, clinician-assigned SCAI staging effectively stratified in-hospital mortality risk, and early changes in SCAI stage further refined prognostication in CS.
Abstract 4146827: Abnormal Liver Stiffness as a Risk Factor for Elevated Hemoglobin A1c in Patients with Fontan Physiology
Authors: Tumuluru Priya , Lockhart Elli , Carr Michael , Kriegermeier Alyssa , Laternser Christina , patel sheetal
Published: November 2024

Background:
Staged surgical palliation resulting in the Fontan operation increases survival in patients born with single ventricle congenital heart disease. Fontan survivors are at higher risk for dysfunction in multiple organ systems. Recent studies have shown higher prevalence of elevated hemoglobin A1c (HbA1c) as a marker of abnormal glucose metabolism in Fontan patients with modifiable associated factors such as obesity and hypertriglyceridemia. However, other risk factors associated with abnormal HbA1c in this population remain unclear. In adults with structurally normal hearts, liver fibrosis and cirrhosis are associated with insulin resistance and elevated HbA1c. One of the known complications of Fontan physiology is elevated systemic venous pressure and resultant liver congestion and fibrosis; however, it is unclear if there is a relationship between liver congestion and abnormal glucose metabolism or insulin resistance in this population. Ultrasound shear wave elastography (SWE) is a non-invasive imaging technique that can quantify the extent of liver fibrosis in patients with structurally normal hearts. Our study aimed to discern a relationship between liver stiffness measured via ultrasound SWE and elevated HbA1c in Fontan patients.

Methods:
Single-center retrospective cross-sectional cohort study including Fontan patients with documented HbA1c testing and liver stiffness measurement (kilopascals, kPa) measured via SWE. Linear correlation and variable comparisons were examined.

Results:
Of 414 Fontan patients evaluated at our center, 190 had at least one HbA1c. Abnormal HbA1c ( >5.6%) was found in 36% (n=70). Additionally, 141 patients had at least one ultrasound SWE and were included in our study. 82 (58%) were male, mean age at time of elastography was 19.46 ± 9.70 years, and 59 (42%) were Caucasian. Patients with abnormal HbA1c had a statistically significant higher median liver stiffness as compared to those with normal HbA1c (13.9± 21.0 kPa vs. 8.9 ±3.04 kPa, p=0.024).

Conclusion:
More than one third of Fontan survivors have abnormal glucose metabolism demonstrated by an elevated HbA1c. Hepatic congestion and fibrosis are known complications of Fontan physiology and increasing liver stiffness by ultrasound elastography may be associated with worsening glucose metabolism. Further investigation is needed to understand how elevated HbA1c and liver stiffness are related and how they affect long-term clinical outcomes in Fontan survivors.
Abstract 4146849: Reassessing Thresholds for Pulmonary Hypertension in Healthy and Early Stage Heart Failure - Project Baseline Health Study
Authors: Alenezi Fawaz , Celestin Bettia , Santana Everton , bagherzadeh shadi , Alajmi Hasan , Salerno Michael , Shah Svati , Rajagopal Sudarshan , Douglas Pamela , Daubert Melissa , Haddad Francois
Published: November 2024

Background:
There is increasing evidence that current thresholds for diagnosing pulmonary hypertension (PH) may underestimate its prevalence and importance in clinical practice.

Objective:
To determine reference values and correlates of right ventricle systolic pressure tricuspid regurgitation (TR) velocity and (RVSP) in the Project Baseline Health Study (PBHS), with a particular focus on diastolic function and preclinical lung and heart diseases.

Methods:
In the PBHS, 2,082 participants underwent transthoracic echocardiography. Of these, 1,132 have tricuspid regurgitation (TR) velocity with reliable estimations of peak TR velocity and RVSP. The association between TR velocity and RVSP and common clinical and TTE parameters were assessed using multidimensional network and multivariable-adjusted regression analyses. Analysis included extensive cardiometabolic risk factors, and diastolic and pulmonary function test parameters. We used the Cox proportional hazard model to analyze the relationship between TR velocity and event-free cardiovascular survival.

Results:
The mean age of the participants was 51 years, with 56.6% female and 62.6% White. Overall, 33.7% had hypertension; 10.8% had diabetes; and 78% had CAC <100. The 97
th
quantile TR velocity was 2.6 m/s and the RVSP was 30mmHg (
fig 1
). While there was a significant increase in TR velocity with age with significant median and upper quantile relationships, the overall nominal change was small. In our study, RVSP was most strongly associated with diastolic parameters (e’ and E/e’) and forced expiratory volume in 1 second (FEV1). In the multivariable-adjusted analysis, age, history of CVD, and e' were independently associated with RVSP after adjustment for traditional risk factors. While TR velocity and RVSP were related to event-free survival on univariable assessment, survival was more closely associated with e’ velocity on multivariable analysis.

Conclusion:
In the multiracial deeply phenotyped PBHS study, TR velocity thresholds were consistent with ASE guidelines and recent The World Alliance Societies of Echocardiography (WASE) studies. The RVSP was mainly related to diastolic parameters and FEV1.
Abstract 4146852: Impact of Left Ventricular Diastolic Function in Pulmonary Arterial Hypertension Outcomes
Authors: Miller Alexandria , Visovatti Scott , Vanderpool Rebecca
Published: November 2024

Introduction:
The demographics of patients with pulmonary arterial hypertension (PAH) is shifting towards older age, increased comorbidity burden, and an increase in the risk of left ventricular (LV) diastolic dysfunction. The H
2
FPEF score and probability were developed to assist in heart failure with preserved ejection fraction (HFpEF) diagnosis. We evaluated the utility of the H
2
FPEF score as well as echocardiographic measures of LV diastolic function in PAH.

Hypothesis:
Development of left-sided heart failure in a population of patients diagnosed with PAH may affect outcomes for those treated with PAH based therapies.

Methods:
Participants with an inpatient admission and a prostacyclin order at the Ohio State University Medical Center between Jan 2020 and Dec. 2022 were included. Chart review was performed to obtain clinical and echocardiographic data. The H
2
FPEF score and probability were calculated at the time of the Echo. Survival analysis was performed (Outcome: PAH related-hospitalization or death). Significant predictors of outcomes were identified using Cox logistic regression analysis. Data are presented as mean ± standard deviation or mean [interquartile range].

Results:
Overall, 140 participants were identified (age: 56±16 years; BMI: 30.04±8.04 kg/m
2
; 74% female) with normal left ejection fraction (LVEF: 63±9%). The majority were on prostacyclin therapy or no therapy at the time of the echo. Median H
2
FPEF score was 3[2-4] and median H
2
FPEF probability was 88[67-95%]. High H
2
FPEF probability was driven by high systolic PA pressure (70±22 mmHg) in the continuous equation (
Fig 1A
). The H
2
FPEF score and probability did not associate with outcomes. However, E/A ratio (HR:0.49(0.26-0.92), p=0.03) and estimated RA pressure (HR:1.1(1-1.1), p=0.02) did significantly associate with outcomes individually and in a multivariable assessment with adjusting for age and BMI (
Fig 1B
).

Conclusions:
The continuous H
2
FPEF probability did not perform well in this inpatient PAH cohort primarily on prostacyclin therapy. Notably measures of right and left atrial function (E/A and estimated RA pressure) did significantly associate with hospitalization and mortality. Future studies in a broader cohort of PAH patients are needed to better understand how diastolic function parameters may impact outcomes.
Abstract 4146866: Associations Between Short-term Outdoor Heat Measures and Arterial Stiffness are Modifed by Neighborhood Greenness: The Green Heart Project
Authors: Riggs Daniel , Sears Clara , Cobbold Sonia , srivastava sanjay , Keith Rachel , Bhatnagar Aruni
Published: November 2024

Introduction:
Accumulating evidence suggests that cardiovascular disease (CVD) risk is associated with climatic variables and the impact of these factors is likely to be increasing with changes in the global climate. Nevertheless, the underlying physiological mechanisms remain unclear, and it remains unknown whether urban greenspaces could contribute to climatic resilience by mitigating these mechanisms. Moreover, to-date most studies assessing CVD risk consider only ambient temperature, which may not fully capture physiologically relevant thermal conditions. Accordingly, using varied measures of heat, our objective was to assess how short-term heat exposure is related to arterial stiffness, and whether these associations are modified by area greenness.

Methods:
Adult participants, aged 25-70 years, were recruited from a neighborhood in Louisville, KY during the summer months of 2018 and 2019. Arterial Stiffness was measured by augmentation index (AIX) via pulse wave analysis in 714 participants. We assessed 7 heat metrics, including ambient temperature, dew point temperature, net effective temperature, Heat Index, and Universal Thermal Climate Index (UTCI), calculated as the 24h mean on the day of participants’ visit. Greenness surrounding participants’ homes was assessed by tree canopy within a 500m buffer. Linear regression was used to estimate associations between heat metrics and arterial stiffness, adjusting for socio-demographic and behavioral factors. Subgroup analysis was performed by tertiles of greenness.

Results:
Participants were predominantly female (61%) and White (77%), with an average age of 49.5 years. The median daily temperature during study visits was 24.4°C (range=12.2 to 28.9°C) and the median daily UTCI was 26.1°C (IQR=5.4°C). The strongest association between heat metrics and AIX was observed for UTCI (2.0% per IQR; 95% CI:0.4, 3.6), followed by net effective temperature (1.8% per IQR; 95% CI: 0.1, 3.6), while dew point temperature had the weakest association (0.6% per IQR; 95% CI: -0.8, 2.0). Stratifying our analysis by tertiles of tree canopy, we observed significant associations between heat metrics and AIX in low canopy areas, with a dose response decrease in associations among medium and high canopy areas.

Conclusion:
Increased arterial stiffness could be an important contributor to excessive CVD risk associated with physiologically relevant measures of heat exposure, which could be mitigated by surrounding greenspaces.
Abstract 4146868: Mapping 3’ untranslated regions reveal compromised alternative polyadenylation in human right ventricle failure
Authors: Thandavarayan Rajarajan , Neupane Rahul , Mahalingam Rajasekaran , Suarez Erik , Wagner Eric , Yalamanchili Hari Krishna , Guha Ashrith
Published: November 2024

Background:
Right ventricular failure (RVF) impacts the prognosis of pulmonary arterial hypertension (PAH). Alternative polyadenylation (APA) generates transcript diversity and is implicated in diseases, including left heart failure. However, understanding genome-wide polyadenylation maps in RVF patients with PAH is limited, with no studies investigating RVF-specific APA events.

Objective:
This study mapped 3' untranslated regions (3'UTRs) to explore APA dynamics in RVF development, comparing healthy donors and RVF from patients with PAH.

Methods and Results:
RV tissues were obtained from patients with failing RV from heart and double lung transplant recipients. Poly(A)-ClickSeq (PAC-seq) RNA sequencing and PolyA-miner algorithm were used. Analysis revealed significant changes in cleavage site usage, identifying 690 genes with altered APA patterns in RVF. Notably, our investigation uncovered a significant finding related to CPSF6, a key factor involved in APA regulation. We observed a substantial lengthening of the 3'UTR in CPSF6, suggesting disrupted polyadenylation events in RVF. Intriguingly, this lengthening coincided with a noticeable decrease in CPSF6 protein levels, indicating a potential regulatory mechanism affecting its expression. Additionally, 530 genes had shortened 3'UTRs enriched for RNA binding and hypertrophic cardiomyopathy pathways, while 160 genes had lengthened 3'UTRs enriched for RNA surveillance and ribosomal RNA binding. Disease-specific APA signatures in RVF patients with PAH were identified.

Conclusion:
The present study highlights the significant role of APA in human RVF exerting its influence on multiple pathways and regulating specific gene expression. These findings offer insights into RVF in PAH patients and may guide the identification of therapeutic targets and strategies for improved management of the condition.
Abstract 4146885: Association of Structural Remodeling and Mitral Annular Disjunction with Significant Premature Ventricular Contraction Burden in Patients with Mitral Valve Prolapse: A Cardiac Magnetic Resonance Imaging Study
Authors: Calcagno Tess , Wang Tom Kai Ming , Kalahasti Vidyasagar , Santangeli Pasquale , Wazni Oussama , Griffin Brian , Chen David , Nguyen Christopher , Sroubek Jakub , Kwon Deborah
Published: November 2024

Background:
Mitral annular disjunction (MAD) is identified by a displacement of the posterior mitral valve annulus into the left atrial wall and is commonly coexisting with mitral valve prolapse (MVP). MAD and MVP are both associated with a high prevalence of premature ventricular complexes (PVCs); however, the underlying mechanisms of increased PVC burden in these patients are unknown. We sought to determine the association between PVC burden, structural heart changes, and late gadolinium enhancement (LGE) in patients with MVP, with and without MAD.

Methods:
We analyzed patients with MVP who underwent cardiac magnetic resonance (CMR) imaging and 24-48hr Holter monitoring from 2020 to 2024. Patients with prior myocardial infarction or ischemic pattern LGE were excluded. LGE was characterized dichotomously as present or absent. Multivariate logistic regression was performed to assess significant independent associations with PVC burden > 5%.

Results:
The study included 107 patients (mean age 53.2 ± 17.6 years old, female (65%), mean LVEDVi 99cc/m
2
, mean LVEF 58±8%, mean mitral regurgitant fraction 23±16%). There were 56 patients with MAD + MVP and 51 with MVP - MAD. PVCs > 5% were noted in 26% of the cohort, and LGE was present in 32%. MAD was present in 52%, and 14% had mitral regurgitant fraction >40%. Multivariate analysis identified MAD and sex-specific LV dilation as independent predictors of significant PVC burden. Mitral regurgitant fraction showed a trend towards significance, while LGE was not significantly associated with PVC burden >5% (Figure 1).

Conclusions:
PVC burden > 5%, MAD, and LGE were prevalent in patients with MVP referred for CMR evaluation. MAD and left ventricular (LV) dilation were independently associated and more strongly predictive of high PVC burden than LGE. Future studies are needed to investigate further structural mechanisms and potential interactions with myocardial fibrosis impacting electrical activity in patients with MVP.
Abstract 4146886: Strive for Silver: A "Measure Accurately" Blood Pressure Peer Learning Accelerator
Authors: Alicki Rebecca , Smith Alison , Montgomery Liz , Overton Katherine
Published: November 2024

Strive for Silver is a structured peer-learning quality improvement effort designed to help health care organizations adopt evidence-based approaches to blood pressure (BP) measurement and improve hypertension control rates. Developed by the American Heart Association (AHA), this opportunity also supports organizations participating in Target: BP™ to achieve annual awards.

Target:
BP is a national initiative created by the AHA and the American Medical Association (AMA) where participants report Controlling High Blood Pressure (MIPS 236) data and attest to 6 evidence-based BP measurement activities as of the prior year. Annual data submission for Target: BP recognizes organizations through awards for control rates ≥70% and/or adoption of ≥4 evidence-based activities.

Organizations that submitted data to Target: BP in 2022 but were ineligible for awards based on performance thresholds were invited to join a Strive for Silver cohort. The initiative consisted of four 1-hour weekly sessions with a brief didactic introduction reviewing the evidence-based measurement activities and related practice tools, followed by interactive breakout groups for collaborative peer-learning.

Beginning in September 2022, 14 organizations participated in the pilot peer-learning series and were monitored via their Target: BP data submissions in 2023 and 2024. Of the 14 pilot organizations, 10 submitted data in both years. When comparing pre-implementation (2022), and post-implementation (2024) Target: BP data submissions, 100% of organizations saw an increase in BP control from baseline, with an average absolute increase of 10.1%, ranging from <1%-31% improved BP control. BP measurement activity attestations increased from an average of 2.4 to 3.9, respectively. A post-assessment survey showed all participants felt that the collaborative was “very valuable.”

The Strive for Silver peer-learning accelerator appears to be an effective approach to helping organizations improve evidence-based practice adoption and improve BP control rates. The model has been replicated with an additional Strive for Silver cohort in 2023 and will continue to be monitored post-intervention. In 2024, Strive for Silver will expand into a Hypertension Control Accelerator with a goal of improving BP control through additional guideline-directed activities. The AHA recognizes Strive for Silver has the potential to expand into other facets of improving BP control as well as other chronic CVD conditions.
Abstract 4146890: Analysis of In-Hospital Outcomes of Transcatheter Edge-to-Edge Repair of Mitral Valve in Patients with and without COVID-19: Insights from the National Inpatient Sample Data (2020-2021)
Authors: Agrawal Siddharth , Raval Maharshi , Shah Aalesh , Sanghvi Labdhi , Bhatia Hitesh , Siddiq Sajid
Published: November 2024

Background:
COVID-19 has introduced new complexities in the management of patients undergoing the transcatheter edge-to-edge repair (TEER) procedure of the mitral valve. This study compares outcomes of mitral valve TEER in patients with and without COVID-19, utilizing data from the National Inpatient Sample (2020-2021).

Methods:
We conducted a retrospective cohort study on 23,465 patients without COVID-19 and 85 patients with COVID-19 undergoing mitral valve TEER. Multivariate logistic regression was employed to compare outcomes, adjusting for potential confounders. Primary outcomes included mortality and major complications, while secondary outcomes encompassed specific procedural complications.

Results:
Patients with COVID-19 were younger (mean age: 73.176 vs. 76.178 years, p-value <0.001) and exhibited differences in gender distribution (male: 64.71% vs. 54.80%, female: 35.29% vs. 45.20%, p=0.4125)

Patients with COVID-19 exhibited a significantly higher prevalence of mortality (OR: 16.331, 95% CI: 4.842-55.08, p<0.001), transfusion (OR: 5.424, 95% CI: 1.511-19.47, p=0.01), post-procedure shock (OR: 7.521, 95% CI: 2.731-20.708, p<0.001), intra-procedure stroke (OR: 7.892, 95% CI: 2.87-21.704, p<0.001), mechanical ventilation (OR: 13.918, 95% CI: 4.072-47.562, p<0.001), acute renal failure (OR: 7.523, 95% CI: 2.454-23.059, p<0.001), sudden cardiac arrest (OR: 26.127, 95% CI: 7.2-94.803, p<0.001), cardiogenic shock (OR: 7.971, 95% CI: 2.894-21.955, p<0.001), septic shock (OR: 23.176, 95% CI: 5.226-102.78, p<0.001), and sepsis (OR: 18.371, 95% CI: 4.926-68.51, p<0.001). The odds of bleeding (OR: 2.983, 95% CI: 0.94-9.47, p=0.064) did not significantly differ between groups.

Patients with COVID-19 had a longer length of stay (LOS) (coefficient: 11.26409 days, p=0.001) and higher total hospitalization cost (coefficient: $230,944.2, 95% CI: $107,037.8-$354,850.5, p<0.001).

Conclusion:
Patients with COVID-19 undergoing mitral valve TEER procedure face elevated risks of mortality, post-procedure shock, stroke, mechanical ventilation, acute renal failure, sudden cardiac arrest, cardiogenic shock, septic shock, and sepsis compared to those without COVID-19. Additionally, they experience longer hospital stays and incur higher total health charges. Clinicians should consider these heightened risks when evaluating the appropriateness of mitral valve TEER in COVID-19 patients. Further research is warranted to explore strategies for risk mitigation in this population.
Abstract 4146924: Endothelial lipase mediates LDLR-independent uptake of LDL by a combination of enzymatic and non-enzymatic mechanisms.
Authors: Lucero Diego , White Olivia , Aligabi Zahra , Burks Kendall , Stitziel Nathan , Goldberg Ira , Remaley Alan
Published: November 2024

Background:
Current lipid-lowering drugs rely on the LDL receptor (LDLR) pathway to lower LDL cholesterol. This leaves patients with null mutations in the LDLR, such as those with homozygous familial hypercholesterolemia (FH), potentially without an effective treatment. Remarkably, inhibitors of angiopoietin-like3 were found to reduce LDL-cholesterol in FH patients in an endothelial lipase (EL)-dependent mechanism. Recently, we found that EL overexpression enhances the cellular uptake of LDL in LDLR-knockout (KO) hepatocytes; however, the mechanism remains unclear.

Aim:
to investigate the mechanisms by which EL mediates LDLR-independent uptake of LDL in hepatocytes.

Methods:
CRISPR/Cas9-generated control and
LDLR
-KO HepG2 cells were transfected by lipofection with an empty plasmid or a plasmid containing the human
LIPG
gene (EL). Cellular uptake of fluorescent human LDL was measured by FACS. To test the contribution of heparan sulfate proteoglycans (HSPG), the cellular uptake of LDL was assessed with and without the pre-incubation with 5 U/ml heparin or a cocktail of heparinases I, II, and II. Furthermore, to analyze the role of EL enzymatic activity, LDL uptake was measured after incubating the cells with 25 µg/ml tetrahydrolipstatin (THL). Finally, we measured the expression of potential receptors by RT-qPCR to explore alternative mechanisms of internalization.

Results:
As previously shown,
LIPG
-transfected
LDLR
-KO hepatocytes showed a 2-fold increase in LDL uptake compared to LDLR-KO cells non-overexpressing EL (p<0.001). LDL uptake was completely blocked by heparinases and heparin in
LDLR
-KO cells regardless of EL over-expression. Treatment with THL partially reduced the cellular LDL uptake in LDLR-KO cells over-expressing EL (p=0.08). In addition, LDLR-KO cells showed a 2-fold increase in the mRNA levels of cluster of differentiation 36 (CD36) (p<0.01), a known scavenger receptor.

Conclusions:
Our findings demonstrate that, in LDLR deficiency, EL mediates the uptake of LDL by a combination of enzymatic and non-enzymatic mechanisms. Furthermore, our data shows that HSPG play a crucial role in the LDLR-independent LDL uptake in hepatocytes, possibly acting as a bridge facilitating LDL internalization. Further studies will determine the role of scavenger receptors in the EL-mediated uptake. These mechanisms may represent a potential druggable target to treat homozygous FH patients.