bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4146173: Effect of Sodium-Glucose Cotransporter-2 Inhibitors on Atrial Fibrillation Recurrence Post-Ablation: A Systematic Review and Meta-Analysis
Authors: Nugooru Sudeep , Ginnaram Shravya , Janga Chaitra , Sevella Prerana , Muhammadzai Hamza , Shah Shreeja , Sabri Muhammad , Alhassani Zaineb , Lee Tyler , Watson Robert
Published: November 2024

Background:
Recurrent atrial fibrillation (AF) occurs in approximately 20 to 40% of patients following catheter ablation. SGLT2 inhibitors (SGLT2i), known for their cardiovascular benefits beyond glycemic control in type 2 diabetes, exhibit multiple pleiotropic effects. These effects offer glucose-independent and direct cardiac protection, potentially enhancing atrial remodeling. Studies suggest that SGLT2 inhibitors may also reduce atrial tachyarrhythmia and lower the risk of recurrence after the initial ablation procedure.

Methods:
We conducted a systematic review and meta-analysis following PRISMA guidelines. Studies were identified from three databases up to May 2024: MEDLINE/PubMed, Scopus, and the Cochrane Central Register of Controlled Trials. Primary outcomes included AF recurrence with secondary outcomes of left ventricular ejection fraction (LVEF) improvement, hospitalizations and adverse events. Data was extracted and analyzed using R/R Studio. Random effects model was utilized to calculate odds ratios (OR) and 95% confidence intervals (CI).

Results:
Six studies were included with 5,456 participants (2,514 in SGLT2i group, 2,942 in control group). SGLT2i significantly reduced AF recurrence (OR = 0.44, 95% CI: 0.29-0.67, I
2
= 65%, p = 0.01). Four studies with 1,044 participants showed a non-significant trend towards LVEF improvement with SGLT2i (OR = 1.99, 95% CI: 0.99-3.99, I
2
= 0%, p = 0.88). Hospitalization rates from five studies (5,184 participants) showed no significant difference between groups (OR = 1.07, 95% CI: 0.63-1.82, I
2
= 46%, p = 0.12). Adverse events in four studies (734 participants) were not significantly higher in the SGLT2i group (OR = 1.19, 95% CI: 0.56-2.52, I
2
= 0%, p = 0.53).

Conclusions:
The results suggest that SGLT2i use significantly reduces AF recurrence following catheter ablation, with a trend toward LVEF improvement, though not statistically significant. Hospitalization rates and adverse events did not significantly differ between the SGLT2i and control groups, indicating a favorable safety profile. These findings support the potential benefit of SGLT2i in post-ablation management. Further large-scale randomized controlled trials are needed to confirm these results.
Abstract 4146187: Ivabradine Associated Atrial Fibrillation Incidence Over 1 Year
Authors: Kaur Jasmeen , Anderson Halie , KIM KIBUM , Radwanski Przemyslaw , Munger Mark
Published: November 2024

Objective:
Ivabradine (IVBD) is a hyperpolarization-activated cyclic nucleotide-gated channel blocker that inhibits the pacemaker I
f
current causing spontaneous depolarization in the sino-atrial node thereby regulating heart rate in patients with heart failure (HF). Previous reports state that IVB use is associated with an increase in risk of atrial fibrillation (AF). This study aims to determine the incidence of ivabradine-associated AF over 1 year in a real-world database of AF naïve patients with HF.

Methods:
Rates of incident AF were determined using Merative Health MarketScan
®
Commercial Claims and Medicare Supplemental Database. Using ICD codes and outpatient medication dispensing records, we extracted HF patients who filled a prescription for IVBD between 01/2015 and 12/2021. Patients with a prior diagnosis of AF before starting IVBD were excluded. The study endpoint was the first diagnosis of AF, defined by ICD 9 and 10 codes, after the index IVBD dispensing. The time to AF was projected using cumulative incidence calculation. We used Kaplan-Meier product limit estimator to calculate AF outcomes at 30, 90, 180, and 365 days from the index IVBD, where patients were censored at the end of enrollment or end of the one-year follow up.

Results:
The analytic cohort at first IVB dispensing included 498 patients with mean (SD) age of 52.27 (12.47). Analytic cohort was slightly more weighted by male with a proportion of 53.2%. The cumulative incidence of AF at 30, 90, 180 and 365 days after the IVB use was 4.91%, 12.16%, 19.24%, and 28.11%, respectively. (Figure)

Conclusions:
Cumulative incidence of AF after IVBD was higher than the published AF incidence among commercially insured HF patients. A comparative safety assessment is warranted to quantify the measure of association for the AF incidence and exposure to IVBD.
Abstract 4146189: Perioperative Aspirin and Coronary Artery Bypass Graft Surgery: An Updated Meta-Analysis of Randomised Controlled Trials
Authors: Gupta Aashray , Zaka Ammar , Lombardo Alexander , Tsimiklis James , Stretton Brandon , Kovoor Joshua , Bacchi Stephen , Ramponi Fabio , Chan Justin , Kovoor Pramesh , Smith Julian , Bennetts Jayme , Maddern Guy
Published: November 2024

Background:
The decision to continue Aspirin before elective coronary artery bypass graft surgery remains contentious due to competing thrombotic and bleeding risks. We performed a contemporary systematic review and meta-analysis to compare outcomes between CABG patients who stopped and continued aspirin before surgery.

Methods:
PubMed, MEDLINE and CENTRAL databases were searched from inception to 4
th
May 2024 for randomized controlled trials (RCTs) comparing patients undergoing CABG who continued preoperative aspirin with those who discontinued before surgery. Studies with co-intervention arms and multivariable-adjusted or propensity matched observational studies were excluded. Summary odds ratios were calculated using a random effects model for dichotomous and continuous variables. Subgroup and sensitivity analyses were conducted in order to explore sources of heterogeneity.

Results:
Sixteen eligible RCTs were included with a total of 6188 patients. Patients who continued Aspirin demonstrated no significant difference in all-cause mortality [OR 1.37 (0.81-2.33)], perioperative myocardial infarction [OR 0.81 (0.55-1.18)] and postoperative blood loss [mean difference 66.12mL (-1.45-133.69)]. No significant difference was observed between low-dose and higher doses of Aspirin. There was minimal heterogeneity amongst included studies (i
2
= 0%, p=0.97 , i
2
=33%, p=0.13 and i
2
=76, p=0.06 respectively). Studies were of low methodological quality according to Cochrane Risk of Bias for Randomized Trials.

Conclusion:
This largest to-date systematic review and meta-analysis found no significant difference for risk of all-cause mortality, perioperative myocardial infarction, and postoperative bleeding between patients continuing and stopping Aspirin before CABG.
Abstract 4146190: Multinational Clinical and Community-based Validation of PRESENT-SHD, an Ensemble Deep Learning Approach for the Detection of Multiple Structural Heart Disorders Using Electrocardiographic Images
Authors: Dhingra Lovedeep , Aminorroaya Arya , Pedroso Camargos Aline , Sangha Veer , Brant Luisa , Barreto Sandhi , Ribeiro Antonio Luiz , Krumholz Harlan , Oikonomou Evangelos , Khera Rohan
Published: November 2024

Background:
Screening for structural heart disorders (SHDs) requires cardiac imaging, which has limited accessibility and requires clinical expertise. We report the multinational validation of PRESENT-SHD, an artificial intelligence-based approach for detecting multiple SHDs from a single image of a 12-lead electrocardiogram (ECG) across clinical settings in the US and a community-based cohort from Brazil.

Methods:
Using paired ECG images and transthoracic echocardiograms (TTEs) from the Yale New Haven Hospital (2015-2023) from 110,228 patients, we developed PRESENT-SHD, an ensemble deep learning approach combining CNN probabilities for individual SHDs with a person’s age and sex, as a single screen for multiple SHDs. SHD was defined as any LV systolic dysfunction (LVEF < 40%), moderate-or-severe left-sided valve disease, or severe LVH (IVSd > 15mm and LV diastolic dysfunction). We validated PRESENT-SHD across patients from 4 distinct hospitals and an outpatient medical network (Northeast Medical Group [NEMG]) in the US and in a large prospective population-based cohort study, the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), who underwent protocolized ECGs and TTEs concurrently.

Results:
We evaluated the model on a single ECG drawn from 8921 individuals at Bridgeport Hospital, 2507 at Greenwich Hospital, 17,856 at Lawrence + Memorial Hospital, 3638 at Westerly Hospital, 21,055 at NEMG, and 3014 in ELSA-Brasil. SHD prevalence ranged from 20-23% at the hospital sites and 22% at the outpatient NEMG. It was 3% in the population-based ELSA-Brasil. In the hospital-based sites, PRESENT-SHD had an AUROC ranging 0.847-0.899, with sensitivities and specifities of 81-85% and 72-80%, respectively. In the outpatient NEMG, the performance was also consistent (AUROC, 0.815 [95% CI, 0.808-0.822], sensitivity 61%, specificity 84%). In ELSA-Brasil, the model had an AUROC of 0.853 (95% CI: 0.808-0.890) with sensitivity and specificity of 63% and 90%, respectively. Model performance was consistent across demographic subgroups.

Conclusion:
PRESENT-SHD maintained excellent performance in identifying SHD on ECG images across diverse populations and clinical settings in the US and Brazil. This demonstrates strong potential as a scalable and accessible tool for SHD screening using digital or printed versions of 12-lead ECGs.
Abstract 4146217: Validation of an Unsupervised Cluster Model of Clinical and Echocardiographic characteristics for Natural Unbiased Stratification of Risk In Heart Failure with Preserved Ejection Fraction
Authors: Arango Juan , Omar Alaa , Alam Loba , Kim Ga Hee , Pinney Sean , Argulian Edgar
Published: November 2024

Background:
We previously reported computational clustering to describe clinically distinct phenotypes of heart failure with preserved ejection fraction (HFpEF). We aimed to validate our prior model exploring the clinical and echocardiographic variations in HFpEF on unseen dataset.

Methods:
Retrospectively, 556 HFpEF patients previously reported [exploration group, Age: 66±17years , 56%females, EF: 63±6%, DOI:10.1016/s0735-1097(19)31580-3] and a new unseen dataset of 1055 HFpEF patients [validation group, Age: 58±17years , 56% females, EF: 60±6%] were studied and followed for a median of 4.7 years for death and cardiac hospitalization. A 2-step unsupervised cluster model previously applied to the exploratory group and composed of 11 echo and clinical variables (age, sex, diabetes, hypertension, hematocrit, creatinine, pulmonary functions, E/A ratio, E/e’ ratio, left atrial volume index, tricuspid regurgitation velocity) was saved and applied to the unseen validation dataset. Clusters were described based on echo and clinical domains.

Results:
The analysis in the exploratory group yielded 8 different clusters with increasing distinct clinical, structural, hemodynamic, as well as adverse event risks as previously reported [low risk females (lowest risk), low risk males, hypertensive females, hypertensive males, multiple risk factor group, diabetes group, pulmonary group, and renal group (highest risk), figure 1 A,B,C]. When applied to the exploratory group, similar clinical, echocardiographic and event rate risk criteria were noted (figure 1 D,E,F). The diagnostic performance of both exploratory and validation models were comparable (AUC=0.724, 0.721, respectively). In the validation group, the clusters also differentiated brain natriuretic peptide and troponin concentration and had progressively worsening H2FPEF score, exercise capacity and exercise induced diastolic dysfunction.

Conclusion:
The current study validates our previous model and confirms the previously reported heterogeneous clinical and echocardiographic phenotypes. Next, computational models such as the one reported should be applied to clinical trials to discover new therapeutic approaches unique to each phenotype.
Abstract 4146266: Long-term temporal trend in Plaque eccentricity assessed through Intravascular ultrasound observations after heart transplantation.
Authors: Nogami Kai , Ozcan Ilke , Kanaji Yoshihisa , Lerman Lilach , Gulati Rajiv , Lerman Amir
Published: November 2024

Background:
Cardiac allograft vasculopathy (CAV) is one of the leading causes of graft failure and death after heart transplantation (HTx). Conventionally, CAV is characterized by concentric intimal thickening, however the long-term progression patterns of plaque morphology are not yet well understood.

Research Question:
This study aimed to assess the plaque morphology, including histology and eccentricity, in a temporal manner post-HTx using virtual histology intravascular ultrasonography (VH-IVUS).

Methods:
We included 50 patients who underwent serial VH-IVUS assessment at three assessment points (A1:0-1 year, A2:3-5 years, A3:7-10 years) after HTx. Differences in VH-IVUS findings between timepoints A1 to A2 (early period) and A2 to A3 (late period) were investigated. Plaque volume index was defined as (plaque volume/vessel volume) × 100%. Eccentricity index (EI) was defined as (maximum intimal thickness – minimum intimal thickness)/maximum intimal thickness and was evaluated in 39 patients with significant plaque (maximal intimal thickness >0.50 mm at the A3) at each timepoint. The serial changes of EI and relationship between EI and other VH-IVUS findings were investigated.

Results:
Of 50 patients, mean age was 51±13 years, 36 (72%) were males. In both early and late periods, the plaque volume (PV) index showed a significant increase, however, the rate of progression was significantly slower in late period. (5.8% [0.9, 13.2] vs 2.4% [-0.2, 7.4], p=0.015). The EI showed a trend of decrease in the early period, compared to increases in the late period (-0.040 [-0.103, 0.004] vs 0.003 [-0.030, 0.052], p=0.036). Patients with EI change in late period higher than median value had significantly lower proportion of fibrous plaque (70.8% [67.2, 75.1] vs 62.7 [55.5, 66.9], p=0.002) and higher dense calcium (1.1% [0.9, 1.9], 4.5% [1.8, 6.9], p=0.022) at A3.

Conclusion:
In heart transplant patients, coronary artery plaque progression in the late period showed more eccentric progression with lower fibrous plaque composition, a pattern commonly observed in typical and conventional coronary atherosclerosis. These findings may provide a novel mechanism and therapeutic insight into the temporal patterns in CAV progression during long term follow up.
Abstract 4146268: Apolipoprotein A1 infusion in patients with Acute Myocardial Infarction: A Systematic Review and Meta-analysis of randomized trials
Authors: Prata Alonzo , Fukunaga Christian , Katsuyama Eric , Coan Ana Carolina , Scardini Pedro Gabriel , Petri Santos Pinheiro Rafael , Falco Neto Wilson , Fernandes Julia , Andrade Naieli , Gioli-Pereira Luciana
Published: November 2024

Background:
Low cholesterol efflux is associated with increased cardiovascular (CV) event risk. CSL112 is a reconstituted, infusible human plasma-derived apolipoprotein A-I that enhances cholesterol efflux, but its efficacy in reducing CV events is unclear. We aim to conduct a systematic review and meta-analysis comparing CSL112 infusions with placebo in acute myocardial infarction patients.

Methods:
We searched Cochrane, Embase and Pubmed databases for randomized controlled trials (RCT). The outcomes of interest were: (1) all-cause mortality; (2) emergent serious adverse events (SAE); and (3) major adverse cardiovascular events (MACE). Heterogeneity was examined with I2 statistics.We pooled risk ratios (RR) with 95% confidence intervals (CI) using a random effects model. Statistical analysis was done using R Studio 4.3.2.

Results:
Three RCTs were included, encompassing 19,557 patients, of whom 10,004 (51%) were in the CSL112 group. Most of the participants were male (74.5%), with a mean age of 65.1 years and a mean follow-up of 11.6 months. In the pooled analysis, there was no significant statistical difference in all-cause mortality (RR 1.06; 95% CI 0.57, 1.97; p=0.86; I2=19%; Fig 1), SAE (RR 1.01; 95% CI 0.84, 1.22; p=0.90; I2=48%; Fig 2A), and MACE (RR 0.94; 95% CI 0.83, 1.06; p=0.32; I2=0%; Fig 2B).

Conclusion:
Our findings suggest that the administration of CSL112 was not associated with a reduction in mortality, SAE or MACE in patients with acute myocardial infarction.
Abstract 4146278: Trends in Obesity-related Cardiovascular Disease Mortality across the United States from 1999-2022: An Analysis of Age, Gender, and Race disparities
Authors: Ayyan Muhammad , Amir Saim , Abdelnour Mark , Zahid Afra , Ehsan Muhammad , Cheema Huzaifa Ahmad , Shahid Abia , Dani Sourbha
Published: November 2024

Background:
Cardiovascular disease (CVD) is a leading cause of mortality worldwide and is inextricably linked to obesity, which is a modifiable risk factor for the pathology. In this study, we aimed to analyze the trends of obesity-related cardiovascular disease mortality in the United States from a period of 1999-2022 and also explored the incongruities between various epidemiological groups.

Methods:
Our study involved accessing multiple cause of mortality records obtained from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiological Research (CDC Wonder) database, specifically focusing on obesity-related cardiovascular mortality, from 1999 to 2022. Age-adjusted mortality rates (AAMR) per 100,000 individuals and associated annual percent changes (APC) for the overall study population were calculated. We further analyzed the data by dividing it into epidemiological groups of age, race, gender, and ethnicity. We further stratified the cardiovascular disease mortality into heart failure, hypertension, ischemic heart disease, and cerebrovascular disease. We used Joinpoint Regression Program to analyze trends in AAMR.

Results:
A total of 33,359 deaths occurred from obesity-related cardiovascular disease in the US from 1999 to 2022. The overall AAMR for obesity-related cardiovascular mortality increased from 1999-2018 with an APC of 5.26, but following this, almost tripled from 2018-2022 with an APC of 14.69. The populations with the highest mortality rates were those in Males, African Americans, non-Hispanics, and the age group of 65-74 years. Among the stratification for the causes of CVD mortality, the highest increase in obesity-related AAMR was observed in hypertensive diseases (APC of 7.56 from 1999-2018, and 15.91 from 2018-2022).

Conclusion:
Obesity-related CVD mortality experienced a moderate incline in the United States. However, since COVID-19, there has been a significant increase in mortality. Persistent demographic and geographic disparities in mortality underscore the need for further investigation and intervention.
Abstract 4146295: Sex disparity in the in-hospital outcomes of patients with chronic kidney disease admitted for ST elevation myocardial infarction: Insights from a large national database
Authors: Rivera Frederick , Ruyeras Jade Monica Marie , Salva Wailea Faye , Balbin Jeremiahdominic , Tang Samantha , Aparece John Paul , Pine Polyn Luz , Tangco Gabriel , Bantayan Nathan Ross , Amigo John Andrew , Ansay Marie Francesca , Matabang Maria Angela , Lerma Edgar , Ong Kenneth , Collado Fareed Moses , Kazory Amir
Published: November 2024

Background:
Previous studies have highlighted the impact of sex differences on the outcomes of patients admitted for ST-elevation myocardial infarction (STEMI). However, there is limited evidence as to whether there is a difference in the outcomes between females and male STEMI patients who have a concomitant diagnosis of chronic kidney disease (CKD) and end-stage renal disease (ESRD).

Research Question:
Does sex affect the outcomes for STEMI patients with concomitant CKD and ESRD?

Methods:
This is a retrospective population-based cohort study that uses the National Inpatient Sample database. CKD patients in the United States hospitalized for STEMI were identified using the International Classification of Diseases, Ninth and Tenth Revision (ICD-9 and 10) codes. Inclusion criteria were adult patients who were hospitalized from 2012 to 2020. A subset of patients with ESRD were also identified. Multivariate regression analysis was performed, with the model adjusted for age and comorbidities. The primary outcome of interest was in-hospital mortality. Secondary outcomes evaluated included ischemic stroke, major bleeding complications, pressor requirement, permanent pacemaker implantation, percutaneous coronary intervention, coronary artery bypass grafting, surgery, pericardiocentesis, mechanical circulatory support, and mechanical ventilation.

Results:
A total of 1,283,255 STEMI patients without CKD, 158,715 STEMI patients with CKD, and 22,690 STEMI patients with ESRD were identified and analyzed. Among patients with STEMI and CKD, females demonstrated higher in-hospital mortality compared to male counterparts (16.7% vs 12.7%, aOR=1.13, 95% CI: 1.05-1.21, p<0.01). Females were also more likely to develop ischemic stroke (4.0% vs 3.0%, aOR=1.16, 95% CI: 1.01-1.34, p=0.04). While there was no sex difference in the in-hospital mortality and most secondary outcomes among STEMI patients with ESRD, female patients in this group were less likely to receive coronary artery bypass grafting (5.0% vs 8.7%, aOR=0.54, 95% CI: 0.42-0.70, p<0.001) and mechanical circulatory support (12.8% vs 17.8%, aOR=0.69, 95% CI: 0.58-0.83, p<0.001).

Conclusion:
Increased in-hospital mortality rates were shown for females admitted for STEMI with CKD. However, for STEMI patients with ESRD, there was no significant difference between males and females with respect to mortality rates. Further research needs to be conducted to better explain this said difference in outcomes.
Abstract 4146297: Cardiovascular Risk Prediction with the Kidney Failure Risk Equation Among Patients with Chronic Kidney Disease: Insights from CRIC
Authors: Correa Simon , Beldhuis Iris , Neuen Brendon , Vaduganathan Muthiah , Wilson F. Perry , Mc Causland Finnian
Published: November 2024

Background:
The Kidney Failure Risk Equation (KFRE) is an established calculator to predict the risk of kidney failure among patients with chronic kidney disease (CKD). Patients with CKD are more likely to die from cardiovascular (CV) causes than from renal causes, and more likely to experience a non-fatal CV event than to progress to kidney failure. The CV predictive ability of the KFRE among patients with CKD is unclear.

Methods:
We investigated the association of the 8-variable (age, sex, urine albumin-creatinine ratio [UACR], estimated glomerular filtration rate [eGFR], serum albumin, serum phosphate, serum bicarbonate, serum calcium) 5-year KFRE with CV disease (CVD) and death among 3,034 patients with CKD (eGFR 15-60 mL/min/1.73m
2
) in the Chronic Renal Insufficiency Cohort (CRIC). KFRE was modeled continuously and by quartiles. CVD was defined as the composite of heart failure hospitalization, myocardial infarction, or stroke. All-cause mortality was a key secondary endpoint.

Results:
Mean eGFR was 39 ±11 mL/min/1.73m
2
; median UACR was 89 mg/g [25-75th percentile 13, 619]. Median KFRE 5-year score was 0.7% [25-75th percentile 0.2, 2.9]. Five-year event rates for the primary endpoint for the lowest to highest quartiles of KFRE were 11.6%, 17.7%, 25%, and 31% (P<0.001). KFRE score (per 1-unit higher log-transformed KFRE score) was associated with a 27% higher risk of CVD (HR 1.27; 95%CI 1.22, 1.33), and a 24% higher risk of death (HR 1.24; 95%CI 1.19, 1.30). When analyzed by quartiles, higher KFRE was associated with more than a 3-fold higher risk of CVD (HR Q4:Q1 3.31; 95%CI 2.67, 4.10), and more than a 3-fold higher risk of death (HR Q4:Q1 3.28; 95%CI 2.62, 4.11).

Conclusions:
Among participants of CRIC, a higher KFRE was associated with a higher risk of CVD and all-cause death. As patients with CKD are at higher risk of both adverse kidney and CV outcomes, this suggests that KFRE could be used as a broad and simple risk-stratification tool for patients with CKD.
Abstract 4146330: Circular-RNA telomerase reverses endothelial senescence
Authors: Qin Weifeng , Cooke John , Mojiri Anahita , Kiss Daniel , Castillo Kathrina
Published: November 2024

Background:
Hutchinson-Gilford Progeria Syndrome (HGPS) is caused by a mutation in LaminA (progerin), and is characterized by accelerated aging and death from coronary or carotid disease in the mid-teens. We have shown that vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) derived from HGPS children manifest many of the hallmarks of aging including telomere erosion, reduced proliferation, impaired function, DNA damage and senescence markers, altered cellular and nuclear morphology, and an aberrant transcriptional profile. These hallmarks of aging are substantially reversed by treatment with telomerase (hTERT) linear RNA,with greater benefit in HGPS cells than the current therapy, lonafarnib. However, linear RNA has a short half-life, which necessitates frequent administration. By contrast, circular (circ) RNA is more stable than linear RNA, and with an internal ribosome entry site can be translated into protein. We hypothesized the hTERT circRNA would provide for longer duration of telomerase expression, and would have a greater benefit for HGPS ECs.

HGPS ECs were treated with hTERT linear or circ RNAs. A single treatment with 1 µg/ml hTERT circRNA reversed multiple stigmata of senescence. However, at day 28 post treatment, the benefit of hTERT circRNA exceeded that of hTERT linear RNA in all measured variables. hTERT circRNA provided for greater recovery of telomere length as determined by quantitative fluorescence in situ hybridization; induced a three-fold greater reduction in beta-gal positive cells and morphologically aberrant nuclei. In HGPS ECs, hTERT circRNA provided for a 2-3 fold greater reduction of senescentfactors, inflammatory cytokines and DNA damage signals, including Progerin, p16, p21, IL-1B, IL-6, IL-8 MCP-1 and gH2A.X. In addition, hTERT circRNA to a greater degree restored NO production, promoted cell proliferation, enhanced angiogenesis and improved LDL uptake. Importantly, mitochondrial functions, as evaluated by the oxidative stress marker (MitoSOX) and mitochondrial membrane potential marker (JC-1 staining), were restored more completely by hTERT circRNA.

Conclusion:
hTERT circRNA is more effective than hTERT linear RNA in rejuvenating senescent ECs, possibly because of its longer half-life. The novel hTERT circRNA is a promising therapy for HGPS and other disorders associated with accelerated vascular aging.
Abstract 4146349: Coronary atheroma burden and structural vascular dysfunction in women with suspected ischemia and no obstructive coronary artery disease.
Authors: Ranasinghe Sachini , Paquin Amelie , Cui Yujie , Maughan Jenna , Mancini G B John , Nelson Michael , Pepine Carl , Wei Janet , Bairey Merz C Noel
Published: November 2024

Background:
Different mechanisms have been proposed to explain abnormal coronary flow reserve (CFR), with authors describing structural vs functional endotypes of coronary microvascular dysfunction (CMD). Epicardial coronary atheroma burden (AB) index is a marker of vascular remodeling confirmed by intravascular ultrasound and is estimated by the measurement of coronary artery tapering. Atheroma burden index is inversely related to CFR in women with suspected ischemia and no obstructive coronary artery disease (INOCA). We hypothesized that AB could help better understand the pathophysiology of these CMD endotypes.

Purpose:
To evaluate the association between epicardial AB, baseline average peak velocity (APV), and resting coronary blood flow (CBF) to better understand endotypes (structural vs functional) of vascular dysfunction.

Methods:
Women with suspected INOCA (n=180) enrolled in two prospective cohort studies (NCT02582021, NCT03876223) who underwent clinically indicated invasive coronary function testing with a Doppler wire measuring CFR, baseline APV and resting CBF, were included in this analysis. Epicardial AB was measured by core laboratory and was derived for the left main and anterior descending coronary segments. The association of AB with CBF and APV was assessed using Pearson’s correlation coefficient.

Results:
Mean age was 55±10 years, body mass index 27.5±5.9 kg/m
2
, 33% had hypertension, 12% diabetes, 18% dyslipidemia and 27% were former smokers. Mean average AB was 1.33±0.37, mean maximal AB was 2.02±0.54 and mean CFR was 3.23±2.35. Both average and maximal AB negatively correlated with resting CBF (r=-0.23, p=0.005; and r=-0.20, p=0.015, respectively) and positively correlated with baseline APV (r=0.23, p=0.002; and r=0.18, p=0.015, respectively). (Figure)

Conclusions:
These results suggest that the findings of a low resting CBF and high baseline APV, among women with suspected INOCA, is associated with a higher epicardial coronary AB. The use of baseline APV and resting CBF could help identify those who are affected by a structural endotype of coronary vascular dysfunction.
Abstract 4146361: Patients demonstrate hesitancy to participate in cognitive assessments in an international coronary bypass surgery graft (CABG) surgery trial
Authors: Ninode Rivera Stephanie , Eslami Sarah , Swartz Richard , Masterson Creber Ruth
Published: November 2024

Introduction:
Coronary artery bypass surgery (CABG) is the most common cardiac surgery in adults, yet it is associated with a range of complications including stroke, cognitive impairment, and dementia. Despite the critical importance of cognitive outcomes, cognition remains understudied in CABG surgery trials, and recruitment for cardiac-related cognitive studies faces substantial challenges.

Objective:
Identify barriers to recruitment in a cognitive auxiliary study in the international Randomized Comparison Of The Clinical Outcome Of Single Vs Multiple Arterial Grafts (ROMA) trial.

Methods:
Semi-structured interviews were conducted with research staff (n=12) involved in the ROMA trial to explore themes related to recruitment barriers into ROMA:Cognition. The average interview length was approximately 25 minutes. Qualitative data were analyzed using a directed content analysis approach, and inter-rater reliability was assessed with Cohen's kappa score based on the five most frequently applied codes.

Results:
Twelve participants were recruited, with a mean age of 48 years. Of these, 90% were female, 60% were from North America, and 30% were from Europe. Key themes identified included: (1) misconceptions of cognition as equivalent to psychiatric disorders, (2) gaps in understanding the importance of measuring cognition for a cardiac-related study, (3) distrust in international data sharing practices, and (4) stigma and apprehension surrounding cognitive decline and mental health issues (Table 1).

Conclusion:
Educational interventions are crucial to improve patient understanding of the importance of cognitive assessments in the context of cardiac surgery. Addressing misconceptions and reducing stigma related to cognitive testing can enhance patient recruitment and engagement in cognitive auxiliary studies. Emphasizing the brain-heart connection and distinguishing cognitive assessment from psychiatric evaluation are essential steps to ensure comprehensive postoperative care and improve outcomes for CABG patients.
Abstract 4146404: The Strain of Pregnancy: Markers of Cardiac Strain and Inflammation in Pregnancies with and without Hypertension – a Case Control Study
Authors: Kovell Lara , Denu Mawulorm , Shankara Sravya , Skaritanov Ekaterina , Berkowitz Julia , Panella Leslie , Maxner Ben , Juraschek Stephen
Published: November 2024

Background:
Pregnancy poses physiologic changes that can precipitate severe or fatal cardiovascular events among women with hypertension (HTN). Understanding mechanisms by which delivery might contribute to these events in women with HTN is critical for prevention.

Aims:
To examine trends in markers of cardiac wall strain or inflammation measured via N-terminal pro b-type natriuretic peptide (NTproBNP) and high-sensitivity C-reactive protein (hs-CRP) in pregnancies with and without HTN.

Methods:
In a prospective, 1:1 case-control design, we enrolled pregnant women with and without HTN between 24-32 weeks gestation (2019-2022). HTN was defined by a clinician diagnosis of chronic or gestational HTN or a baseline blood pressure (BP) ≥140/90 mm Hg. The control group (no HTN) had a systolic BP <120 mm Hg and no diagnosis of HTN. Serum was collected at baseline, pre-delivery (at the delivery admission), and postpartum day 1. We used mixed effects tobit models to compare log-transformed NTproBNP and hs-CRP, across HTN groups and over time, adjusted for age and BMI.

Results:
The mean age of the HTN group (N=38) was 33.6 (SD 5.4) vs. 30.3 (5.8) years for the no HTN group (N=38). Mean (SD) baseline BP was 131.1 (14.7)/88.2 (13.5) for the HTN group and 110.1 (7.2)/70.9 (8.2) mm Hg for no HTN. At baseline, NTproBNP was 29.6 (4.2) in the HTN group and 29.5 (4.4) pg/mL in the no HTN group (
Figure
). Compared to baseline, there was a non-significant change in NTproBNP pre-delivery and an increase at postpartum for both groups (114% [49-208%] for HTN, 120% [51-219%] for no HTN). Baseline hs-CRP was 6.9 (1.1) in the HTN group and 5.1 (0.8) mg/L in the no HTN group. Compared to baseline, there was a non-significant change in hs-CRP pre-delivery and an increase at postpartum for both groups (550% [337-867%] for HTN, 662% [407-1050%] for no HTN). Across all time points, there were no significant differences in NTproBNP and hs-CRP between the two groups.

Conclusion:
While HTN was not associated with greater cardiac wall strain or inflammation compared to no HTN, delivery alone led to an approximately 2-fold increase in cardiac wall strain and 7–fold increase in inflammation from mid-pregnancy to immediate postpartum.
Abstract 4146405: Blood Volume Prediction Equations Do Not Precisely Estimate Blood Volume in Adults with Heart Failure with Preserved Ejection Fraction (HFpEF)
Authors: Sooda Meera , Wakeham Denis , Samels Mitchel , Brazile Tiffany , Leahy Michael , Manferdelli Giorgio , Macnamara James , Sarma Satyam , Hearon Christopher , Levine Benjamin
Published: November 2024

Background:
In heart failure with preserved ejection fraction (HFpEF) expanded blood volume (BV) can result in significant hemodynamic stress that contributes to disease pathogenesis. Due to the lack of routine access to methods of BV measurement, clinicians typically rely on BV prediction equations. However, current prediction equations do not accurately or precisely estimate BV, or its components, in HFpEF. The aim of our analysis was to directly measure blood volume in adults with HFpEF and compare newly developed BV prediction equations (Oberholzer
et al
., 2023) to previously validated equations (Nadler and Pearson).

Methods:
In 52 adults with HFpEF (65% female; age: 70±7 years; BMI: 38±7[GM1] kg/m
2
) we assessed total hemoglobin mass via carbon monoxide rebreathing, enabling calculation of BV. We estimated BV with the Oberholzer simple (age, sex, height and body mass) and clinical (age, height, and lean mass) equations, as well as Nadler and Pearson equations. Data were compared via either paired or independent samples t-tests or a one-way ANOVA with values presented as mean [95% CI] or mean ± standard deviation.

Results:
Unlike the Oberholzer simple (-226 [-507 – 55] ml,
P
=0.113) equation, the Oberholzer clinical equation significantly underestimated measured BV (-513 [-807 – 219] ml,
P
=0.001); both of which were imprecise with large typical error values (TE; Simple: 11%; Clinical: 11%). Compared to the Oberholzer equations, the mean estimated-measured difference was greater with the Nadler (
P
<0.001; TE=12%) and Pearson (
P
<0.001; TE=11%) equations (Figure 1A). We observed greater accuracy and precision of all prediction equations for females compared to males (Figure 1B-C): Oberholzer simple (
P
=0.070); Oberholzer clinical (
P
=0.047); Nadler (
P
<0.001); Pearson (
P
<0.043).

Conclusions:
The Oberholzer simple equation yielded the most accurate and precise prediction of BV in adults with HFpEF, with greater accuracy and precision in females. However, all prediction equations remain imprecise with substantial error up to 11% and should therefore be used with caution. As such, there needs to be more widespread measurement of BV to refine prediction equations utilized in clinical settings.
Abstract 4146428: Molecular Imaging of Atherosclerotic Plaque Erosion Using Hyaluronan-Targeted Near-Infrared Fluorescence
Authors: Maino Alessandro , Ha Khanh , Iwamoto Yoshiko , Mauskapf Adam , Ramesh Ashvita , McCarthy Jason , Jaffer Farouc
Published: November 2024

Introduction:
Plaque erosion (PE) has a distinct pathogenesis, clinical presentation, and prognosis than other acute coronary syndrome (ACS) causes such as plaque rupture (PR). At present the ability to distinguish between PE and PR using in vivo imaging is limited. A critical feature of PE is the enrichment of hyaluronic acid (HA) at the luminal interface, which is poorly present in the other types of plaque. To better resolve mechanisms of ACS in vivo, we designed and investigated a new hyaluronan-targeted near-infrared fluorescence (NIRF) molecular imaging agent and tested the agent in vitro, in mouse PE in vivo, and in resected human carotid specimens. NIRF has emerged as a translational intravascular imaging modality that allows visualization of plaque pathobiology in vivo.

Methods:
The NIRF agent was generated via microwave-assisted solid phase peptide synthesis and was conjugated to the NIR fluorophore CyAl5 (ex/em 643/661 nm), to yield the hyaluronan-targeted NIRF agent (HAT-CyAl5). In vitro binding of HAT-CyAl5 to HA was assessed by fluorescence reflectance imaging (FRI). HAT-CyAl5 or a scramble control peptide-CyAl5 (scrambled-CyAl5) were intravenously injected in an established electrical injury-based mouse model of carotid artery PE; intravital microscopy (IVM, n=7) was performed in mice injected with HAT-CyAl5 (n=4) or scrambled-CyAl5 (n=3). Next, freshly resected human carotid specimens were incubated with HAT-CyAl5 (n=4) or PBS (n=4). Histological analyses then assessed specific binding of HAT-CyAl5 in murine PE and human atheroma.

Results:
The blood half-life of HAT-CyAl5 was 5.7 minutes (95% CI, 3.4-9.8min). In vitro HA binding analyses showed a significant higher target-to-background ratio (TBR) in the HAT-CyAl5 group (P < 0.03 vs. Scrambled-CyAl5). In carotid PE undergoing IVM, HAT-CyAl5 double the TBR in vivo (4.7 ±1.36 vs. 2.38 ± 0.17 Scrambled-CyAl5, P< 0.05). In human carotid plaques, HAT-CyAl5 markedly increased plaque NIRF signal (TBR
post-incubation - pre-incubation
4.95 ±3.36 vs. 0.00 ± 0.15 PBS, P< 0.03). Histology of human plaques showed that HAT-CyAl5 localized well with HA immunohistochemical expression.

Conclusion:
HAT-CyAl5 is a new NIRF probe that avidly and specifically binds HA in murine PE in vivo and in human plaques. HAT-CyAl5 coupled with intravascular NIRF imaging has the potential to specifically diagnose PE and provide new insights into the pathogenesis of PE.
Abstract 4146430: Microglia Mediated Neuroinflammation: Understanding Mechanisms of Augmented Sympathetic Nerve Activity in Chronic Kidney Disease
Authors: Sharma Swati , Paloczi Janos , McTernan Patrick , Mohandas Rajesh
Published: November 2024

Background:
Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). Excess sympathetic nerve activity (SNA) is thought to be a major mechanism for elevated cardiovascular risk in these patients. However, the mechanisms that drive excess SNA in patients with CKD are not well understood. A growing body of evidence suggests that CKD is associated with inflammation and immune dysfunction. However, the role of neuroinflammation in CKD has not been studied.

Hypothesis:
We hypothesize that microglial activation and neuroinflammation underlies excess sympathetic activity in chronic kidney disease (CKD).

Aim:
Understand the extent to which microglia mediate neuroinflammation and contribute to excess SNA in CKD.

Methods:
C57/BL6 mice (18-22 gm, 8 weeks old) were randomized to 0.2% adenine in casein (CKD) or continued on casein-only diet (Control) for 2, 4 or 6 weeks. SNA was assessed by heart rate variability, as determined by spectral analysis of the electrocardiogram (Low Frequency / High-Frequency HF/LF ratio) and catecholamine levels (ELISA). Neuroinflammation will be evaluated by profiling the cytokines/chemokines in serum and CSF using Luminex cytokine array. Microglia phenotyping was performed by flow cytometry. Renal function was quantified by serum creatinine and cystatin C levels.

Results:
The adenine model resulted in significant CKD by 2 weeks. SNA was increased by week 4 as evidenced by an increased LF/HF ratio [0.46 ± 0.1 in CKD vs. 0.21 ± 0.05 Controls] P = 0.02. There were no differences in SNA at 2 weeks. However, changes in microglia were evident as early as 2 weeks, with CKD mice showing significantly increased numbers of activated microglia (CD11b+ CD45low/int P2RY12+ CD86+) (P = 0.007). The areas of the brain that control sympathetic output showed excess microglia.

Conclusion(s):
Our data suggests that CKD is associated with neuroinflammation in sympathetic areas of the brain. Microglia activation precedes increases in SNA. Experiments to examine the effect of microglia depletion on SNA are ongoing. Together, these experiments will provide comprehensive insight into how microglial function and neuroinflammation synergize to increase SNA in CKD.
Abstract 4146434: Factors Associated with Subsequent Catheterization and Identification of High-Grade Obstructive Coronary Artery Disease in Patients Without Known Coronary Disease and a Low to Moderate Short-Term Risk PET/CT Stress Test
Authors: Knowlton Kirk , Le Viet , Mason Steve , Meredith Kent , Hu Peter , Knight Stacey
Published: November 2024

Background:
PET/CT stress test may be performed to risk stratify patients including those without known coronary artery disease (CAD) who may be at risk for short-term adverse cardiac events. In patients with low- to moderate (LTM) risk for short-term MACE and without a known history of CAD, a small percentage of these patients will undergo a coronary angiogram within 90-days, of which some will be diagnosed with high-grade stenosis. The purpose of this study is to determine factors associated with this approach and findings.

Methods:
Patients without a history of known CAD (n=43,271) undergoing a PET/CT from 2018-2023 at Intermountain Health, with scan interpreted clinically as LTM short-term risk for adverse cardiac events, and ischemic burden <10% (n=38,388) were studied. To determine factors associated with a decision to proceed with a coronary angiogram and the presence of high-grade CAD (>70% stenosis in any vessel), an a priori list of clinical data and PET/CT results were examined.

Results:
Within 90 days of the LTM risk PET/CT, 3,163 (8.2%) had a coronary angiogram. Of these, 806 (25.5% of angiograms and 2.1% of total LTM) had high-grade CAD. The PET/CT ancillary findings were associated with the largest odds of performing an angiogram and the presence of high-grade CAD (Tables). Factors most likely to be associated with performing an angiogram were an ischemic burden of 7.5-10% (adjusted-OR [adj. OR]=11.54), coronary artery calcification (CAC) score of >300 (adj.-OR =1.62), and myocardial blood flow (MBF) of <1.5 (adj. OR=2.25 compared to >MBF 2.3). Other clinical parameters associated, after adjustment, with an angiogram were age, male sex, hypertension, elevated troponin, and inpatient status. Many of the same factors were found to be associated with the identification of high-grade CAD. However, being an inpatient was associated with increased odds of angiogram but a decrease in odds of high-grade CAD.

Conclusions:
In patients without a known history of CAD who underwent PET/CT clinically adjudicated as LTM short-term risk and ischemic burden <10% of cardiac events, subsequent coronary angiograms and high-grade CAD were not common. High-grade CAD was associated with PET/CT findings of ischemic burden of 7.5%-10%, CAC, and MBF. This indicates that attention to these findings may have a role in the decision to perform catheterization to identify high-grade CAD despite an interpretation of LTM short-term risk.
Abstract 4146436: Echocardiography Analysis of Anabolic-Androgenic Steroids Effects on Cardiac Structure and Function in Athletes: A Systematic Review and Meta-Analysis
Authors: Cavalcante Douglas , Fante Gustavo Eduardo , Melo Altair , Romariz Livia , De Oliveira Fischer Bacca Caroline
Published: November 2024

Introduction:
Anabolic-androgenic steroids (AAS) have been used for performance enhancement by athletes, exposing them to potential cardiovascular effects and structural changes. Some athletes also present cardiac structural or functional changes secondary to resistance training. Therefore, the true effect of AAS in echocardiographic parameters among athletes remains unclear.

Research Question:
What are the changes in echocardiographic parameters in athletes who use AAS compared with those who do not use AAS.

Objective:
We aimed to perform a systematic review and meta-analysis comparing use with no use of AAS in athletes for echocardiography parameters.

Methods:
PubMed, Embase, and Cochrane were systematically searched for studies that assessed echocardiographic changes in athletes who used AAS compared to non-users. We computed mean differences (MD) for all continuous outcomes, with 95% confidence intervals (CI) pooled under a random-effects model. Heterogeneity was assessed with I
2
statistics. Statistical analysis was performed using Review Manager (Cochrane Collaboration).

Results:
We included 13 studies with 742 male athletes (401 AAS vs 341 control; mean age 33.4 and 32.4 years respectively). AAS was associated with a decrease left ventricular (LV) ejection fraction (MD -3.17%; 95% CI -5.51, -0.83%; p=0.008; Figure 1A) and global longitudinal strain (MD 3.58%; 95% CI 2.95, 4.20%; p<0.001; Figure 1B) when compared to no use. Athletes who used AAS also had an increased septal wall thickness (MD 0.98 mm; 95% CI 0.06, 1.9 mm; p=0.04; Figure 2A.), posterior wall thickness (MD 1.16 mm; 95% CI 0.57, 1.75 mm; p<0.01; Figure 2B) and LV mass (MD 42.9g; 95% CI 23.2, 62.5g; p<0.0001; Figure 2C) when compared to non-user athletes. LV end-diastolic diameter (MD 1.26mm; 95% CI 0.00, 2.51mm; p=0.05; Figure 2D) showed a tendency to increase in AAS users, but with no significant difference.

Conclusion:
AAS use among athletes is associated with reduced LV function and increased LV hypertrophy and overload, compared with athletes who do not use AAS.