bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4135215: Eosinophilic Coronary Periarteritis (ECPA): An Under-recognized Coronary Disease with Fatal Consequences
Authors: Henriquez Wilfredo , Hade Allison , Booth Dana , Hsu Pamela
Published: November 2024

Clinical presentation:
A 50-year-old male with a paraesophageal hernia and grade D esophagitis presented to the ER with complaints of heartburn. He subsequently went into cardiac arrest and was diagnosed with a hemopericardium with tamponade physiology from a ruptured right coronary artery (RCA).

Imaging Findings:
Initial CT of the chest found a 1.5x1.5 cm dilation of the proximal RCA (Fig1A). Post cardiac arrest, repeat CT of the chest revealed an interval increase of the proximal RCA measuring 3.5x3.5 cm and a moderate-to-large hemopericardium (Fig1B). An emergent limited TEE demonstrated a large circumferential hemopericardium and biventricular standstill.

Decision-making:
In the ER, the initial symptoms resolved and he remained under observation. Hours later, he became bradycardic with a heart in the 20s and was found unresponsive. ACLS was activated and the patient was emergently cannulated and ECMO was initiated due to refractory cardiac arrest. Despite efforts from a multidisciplinary team including cardiology, cardiothoracic surgery and cardiac critical care, ROSC could not be achieved thus portending a poor prognosis. The family decided to withdraw care and the patient expired. Autopsy revealed a 925 mL hemopericardium from a ruptured 3.5 cm severely aneurysmal RCA and other remarkable findings included a 2 cm proximal aneurysm of left anterior descending artery and a 1 cm proximal aneurysm of left circumflex artery (Fig2A,B). Genetic testing for connective tissue disease was negative. Histopathology showed an eosinophilic predominant inflammatory infiltrate of the adventitia suggesting periarteritis (Fig2C) without signs of vasculitis in other organs.

Conclusion:
ECPA (eosinophilic coronary periarteritis) is a fatal entity with reported cases of sudden cardiac death and findings of vessel medial degeneration and coronary dissection. This case raises awareness of an under-recognized condition with limited guidance in diagnostic and therapeutic interventions.
Abstract 4135229: Endothelial glycocalyx shedding during ST-elevation acute myocardial infarction
Authors: Miranda Carlos
Published: November 2024

Background:
Endothelial glycocalyx (eGC) is a layer of glycosaminoglycans adhered to proteoglycans that cover the inner surface of the vessels. The integrity of this structure sustains some vascular properties such as shear stress-induced nitric oxide release and the prevention of platelets and neutrophils adhesion on the vessel surface. eGC shedding could contribute to atherosclerotic plaque vulnerability and acute myocardial infarction (AMI) installation. This research investigated whether acute eGC damage and microvascular dysfunction occurred during AMI.

Methods:
Sublingual microcirculation was assessed through Capiscope HCVS Handheld Video Capillaroscopy System (KK Technology, Honiton, UK) during the first 72h of hospital admission because of ST-elevation AMI (before) and repeated around six months later (after). All images were automatically analyzed using the GlycoCheck (Alpine, UT, USA), which estimated the perfused vascular density (PVD), the red blood cell (RBC) filling of the vessels, the perfused boundary region (PBR) in µm, an inverse parameter of the eGC thickness; and the microvascular health score (MVHS). This score ranges from 0-10; the lower its numerical value, the greater the microvascular impairment.

Results:
Twenty patients were included (61±10 years old, 85% males, 55% anterior AMI, 70% hypertension, 25% diabetes, 45% current smoker, all underwent primary PCI). The time between the two sublingual assessments was 188±31 days. The PBR [1.96±0.22µm vs. 1.84±0.19µm]; p=0.047 and flow-adjusted PBR [1.40±0.25µm vs. 1.24±0.16µm]; p=0.045 decreased statistically significant over time. The RBC filling [71.56±4.33% vs. 74.02±3.88%]; p=0.016 and the MVHS [4.28 (interquartile range (IRQ) 3.38-4.90) vs. 5.04 (IQR 4.37-6.00)]; p=0.044 increased statistically significant over time. The PVD [500±86 x10-2µm/mm vs. 522±84x10-2µm/mm]; p=0.255 did not modify over time.

Conclusion:
This finding was compatible with eGC shedding and microvascular dysfunction during AMI and later reconstitution of this structure after six months.
Abstract 4135307: Integrating genomics and proteomics to identify causal proteins and biologic pathways for incident atrial fibrillation in chronic kidney disease
Authors: Petzl Adrian , Norby Faye , Ren Yue , Wang Jianqiao , Dubin Ruth , Li Hongzhe , Segal Mark , Chen Lin , Alonso Alvaro , Surapaneni Aditya , Coresh Joe , Grams Morgan , Feldman Harold , Bansal Nisha , Marchlinski Francis , Go Alan , Ganz Peter , Deo Rajat
Published: November 2024

Introduction/ Background:
Individuals with chronic kidney disease (CKD) are at an increased risk for developing atrial fibrillation (AF).

Research Objective:
By integrating genomics and proteomics, we sought to identify proteins and biologic pathways causally linked to the development of AF in the CKD population.

Methods / Approach:
We measured 4638 unique plasma proteins using SomaScan v.4.0 in participants (ppts) with CKD and no prior AF from 2 cohorts: Chronic Renal Insufficiency Cohort (CRIC, n=2654) and Atherosclerosis Risk in Communities Cohort (ARIC, n=1326). Associations of individual proteins with incident AF were analyzed using Cox regression after adjustment for demographics, comorbidities, and kidney function. Among proteins independently associated with incident AF in both cohorts, we tested for causality using two-sample Mendelian Randomization (MR). Previously published genome wide association studies (GWAS) were used to identify both protein quantitative loci (cis-pQTL) and summary statistics for incident AF. We then used Ingenuity Pathway Analysis to compare proteins and pathways associated with both incident AF and an increase in left atrial (LA) size across serial echocardiograms in CRIC.

Results / Data:
Over the 5-year analytic period, incident AF occurred in 150 ppts from CRIC and 140 ppts from ARIC. Eight proteins were independently associated with AF in both cohorts: NT-proBNP, SVEP1, TAGLN, TFF3, WAP4, MMP-12, CILP2 and NELL-1. Of these, 3 were significant in MR analysis (Figure 1): CILP2 and MMP-12 maintain structural integrity of the extracellular matrix in the heart and modulate the fibrotic response; NELL-1 is responsible for cell signaling in kidney disease and cardiovascular development. In addition, leading biologic pathways implicated in both development of AF and increase in LA size included systemic fibrosis (p=1.7x10
-4
for AF and 2.3 x10
-4
for LA); regulation of insulin-like growth factor (p=2.3 x10
-4
for AF and p=4.3 x10
-7
for LA) and extracellular matrix degradation (p=5.5 x10
-4
for AF and p=4.2 x10
-4
for LA).

Conclusions:
Trans-omics analyses identified 3 proteins causally associated with developing AF in the CKD population. Also, several pathways involved with cardiac remodeling and fibrosis are common to the development of AF and LA remodeling.
Abstract 4135335: A randomized trial of expedited intra-arrest transfer versus more extended on-scene resuscitation for refractory out of hospital cardiac arrest: the EVIDENCE Study
Authors: Dennis Mark , Burns Brian , Marschner Ian , Keech Anthony
Published: November 2024

Background:
Refractory out-of-hospital cardiac arrest (OHCA) has poor outcomes. The benefit of expedited intra-arrest transport with ongoing resuscitation versus more extended on-scene resuscitation for refractory OHCA is not clear.

Methods:
In this Phase III, multi-center (15 hospitals), randomized, controlled trial conducted in Sydney, Australia, we assigned patients with refractory out-of-hospital cardiac arrest to receive either expedited intra-arrest transport, with mechanical cardiopulmonary resuscitation, to a cardiac catherization-capable hospital for coronary angiography and, where available, extracorporeal membrane oxygenation (ECMO) cardiopulmonary resuscitation (ECPR) or more extended on-scene conventional CPR (advanced cardiac life support). Eligible patients were between 18 and 70 years of age, had received bystander CPR, initial rhythm VT/VF/PEA, and did not have a return of spontaneous circulation after 15 minutes of CPR, or three rounds of resuscitation. The primary outcome was survival with a favorable neurologic outcome, defined as a Cerebral Performance Category score of 1 or 2 at hospital discharge. Analyses were performed on an intention-to-treat basis.

Results:
One hundred and ninety-seven (197) eligible patients were randomized (median age, 57.0 years; 77 [81%] men), 149 VT/VF (76%). Ninety-five were assigned to receive expedited transfer and 102 to receive conventional CPR. Ten patients in the expedited arms and 6 patients in the conventional arm received ECPR at hospital. At hospital discharge, 15 patients (14.7%) in the expedited transfer group (median on scene time 26 mins) were alive with a favorable neurologic outcome, as compared with 15 patients (15.8%) (median on-scene time 36 minutes). This treatment difference was small and statistically insignificant (risk difference -1.1% [95% CI: -12.2% to 10.0%]), adjusted relative risk 0.95 [p=0.87, 95% CI: 0.50 to 1.8].

Conclusions:
Among patients with refractory out-of-hospital cardiac arrest, expedited intra-arrest transport did not significantly improve survival with neurologically favorable outcome at discharge compared with more extended on-scene resuscitation. However, clinically relevant differences could still be consistent with our results.
Abstract 4135353: Accuracy, Hallucinations, and Misgeneralizations of Large Language Models in Reviewing Cardiology Literature
Authors: Fang Spencer , Pillai Joshua , Mahin Baharullah , Kim Sarah
Published: November 2024

Introduction:
The text generation abilities of large language models (LLMs), such as ChatGPT, can streamline the process of research and potentially expedite reviewing literature.

Methods:
We evaluated the capabilities of LLMs and their major susceptibilities—hallucination and goal misgeneralization—in reviewing cardiology literature. We asked 30 comprehensive questions (n=600) regarding findings from notable cardiovascular studies and randomized controlled trials (n=20) from 2016-2020 to GPT-4, GPT-3.5, and LLaMa 3. The question groups followed a format where the initial question checked for accuracy in identification, second for misgeneralization, and third for hallucination (Table 1). All questions were communicated in individual interfaces of the models to retain independence and prevent bias. Responses were then reviewed for accuracy, misgeneralizations, and hallucinations.

Results:
GPT-4 and GPT-3.5 did not significantly differ in accuracy (55% vs. 40%, p=0.527), with a low association (φ=0.1) and an odds ratio (OR) of 1.83 (95% CI: 0.522-6.434). Similar results were observed between GPT-4 and LLaMa 3 (55% vs. 30%, p=0.201), with an OR of 2.85 (95% CI: 0.776-10.467). For generalization, GPT-4 and GPT-3.5 also did not significantly differ (30% vs. 35%, p=0.999), with a low association (φ=0.001) and an OR of 0.80 (95% CI: 0.211-2.998). Likewise, GPT-4 and LLaMa 3 showed no significant difference (30% vs. 25%, p=0.999), with an OR of 1.29 (95% CI: 0.319-5.174). For non-hallucinations, GPT-4 and GPT-3.5 did not significantly differ (30% vs. 60%, p=0.187), with a low association (φ=0.214) and an OR of 0.33 (95% CI: 0.088-1.256). Lastly, GPT-4 and LLaMa 3 showed no significant difference (30% vs. 25%, p=0.836), with an OR of 1.50 (95% CI: 0.36-6.13). Overall, all models did not differ in accuracy, misgeneralization, and hallucination. Given the moderate susceptibilities of these models, LLMs require more training before realistic usage in cardiology.

Conclusions:
LLMs show potential for identifying cardiology studies, but moderate hallucination and misgeneralization render them unsuitable for this purpose. Without resolution of susceptibilities (<5-10%), LLMs remain unrealistic for accurately reviewing literature.
Abstract 4135444: Sex Disparities in Enrollment of Cardiovascular Trials: A Meta-Analysis of ClinicalTrials.gov Listings
Authors: Chi Gerald , Lee Jane , Gibson Charles
Published: November 2024

Background:
Despite increasing recognition of sex differences in the burden of cardiovascular (CV) diseases, women have historically been underrepresented in clinical trials.

Aims:
The study aimed to systematically quantify the extent of sex disparity in the enrollment of CV trials and explore the annual enrollment trends of women in CV trials.

Methods:
The analysis included studies that: (1) were registered in ClinicalTrials.gov up to February 2024; (2) were randomized trials involving ≥1 intervention; (3) investigated ≥1 CV condition, as determined by Medical Subject Heading descriptors. The exclusion criteria were: (1) studies without available enrollment information; (2) studies exclusively enrolling men or women; and (3) studies with ≤100 participants. We computed enrollment disparity difference (EDD), defined as the difference between the proportion of women in trial participants and the proportion of women with CV diseases in the general population, based on the Global Burden of Disease estimates matched by country/geographic region and enrollment period. Random-effects meta-analysis was performed to summarize the overall enrollment disparity. Subgroup analysis by trial characteristics was conducted. Meta-regression was used to assess the association of enrollment disparity with the start year of the trials.

Results:
A total of 1,687 CV trials were identified from 484,781 studies. Among 2,198,317 trial participants for whom sex was reported, 819,570 (37.3%) were women. EDD in CV trials was -0.105 (95% CI, -0.113 to -0.097), indicating that women were under-enrolled by 10.5% (Figure 1). Except for valvular heart disease trials, disparities were evident across other CV disease trials, with the most remarkable under-enrollment of women in peripheral artery disease trials (-0.302 [95% CI, -0.324 to -0.279]). Disparities were more prominent in trials with larger sample sizes, longer study durations, device or procedural interventions, and data monitoring committee oversight (p<0.001 for subgroup differences; Figure 2). There was a significant yet modest improvement in the representation of women over time (increase of 0.0028 [95% CI, 0.0011 to 0.0045] in EDD per start year of trials; p=0.001; Figure 3).

Conclusion:
Women remain substantially underrepresented in CV trials, particularly in peripheral artery disease trials. The findings underscore the imperative for interventions to mitigate sex inequity in the enrollment of CV trials.
Abstract 4135465: Efficacy of SGLT-2 inhibitors combined with percutaneous coronary intervention on clinical and echocardiographic parameters in patients with acute myocardial infarction: A systematic review and meta-analysis
Authors: Qazi Shurjeel , Samad Muhammad Ammar , Ansari Huzaifa , Mahboob Eman , Siddiqui Abdul Hannan , Qazii Sana , Ahmad Adeel , Rahman Asad , Ahmed Mushood , Ahmed Raheel , alam mahboob
Published: November 2024

Background:
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown benefits in improving cardiovascular outcomes in heart failure (HF) patients and may mitigate symptom progression in myocardial infarction (MI). However, their efficacy in acute MI patients undergoing percutaneous coronary intervention (PCI) is unclear. This study aims to evaluate whether SGLT2i combined with PCI improves clinical and echocardiographic outcomes.

Methods:
A comprehensive search of electronic databases, PubMed, Cochrane Central and SCOPUS was conducted from inception till May 2024. The study was conducted adhering to the PRISMA guidelines. The clinical benefit of PCI plus SGLT2i was assessed through risk reduction of acute kidney injury (AKI), CV death (CVD), hospitalization due to HF (hHF), all-cause mortality (ACM), and revascularization. Echocardiographic outcomes assessed were change in left ventricular ejection fraction (LVEF) and LV end-diastolic volume (LVEDV). Results were presented as risk ratios (RR) along with their 95% CI for dichotomous data while weighted mean difference (WMD) were reported for continuous outcomes. The data was aggregated using a random effects model.

Results:
Our analysis included eleven records comprising 6,411 participants. The results indicated that PCI plus SGLT2i significantly reduced the risk of AKI (RR: 0.66, 95% CI: [0.52, 0.83], p<0.01) and ACM (RR: 0.54, 95% CI: [0.4, 0.7], p<0.01) compared to PCI alone. However, the reduction in risk for CVD was not statistically significant (RR: 0.56, 95% CI: [0.2, 1.1], p=0.09), as was the case for hHF (RR: 0.65, 95% CI: [0.3, 1], p=0.07). Additionally, there was no significant difference in the risk of revascularization between the two groups (RR: 2.9, 95% CI: [0.62, 14.39], p=0.17). PCI plus SGLT2i was also significantly associated with an increase in LVEF (WMD: 2.73, 95% CI: [1.09, 4.36], p<0.01) and decrease in LVEDV (WMD: -8.0, 95% CI: [-13.17, -2.90], p<0.02).

Conclusion:
Our study demonstrates that SGLT2i administration in MI patients undergoing PCI leads to improved renal and mortality outcomes, along with enhanced cardiac function. These benefits are hypothesized to result from kidney-mediated natriuretic effects, improved blood flow regulation, reduced endothelial dysfunction, and decreased arterial stiffness, which optimize cardiac function. We recommend future studies with larger sample sizes and longer follow-ups to assess the long-term benefits of SGLT2i combined with PCI.
Abstract 4135525: Bridging the Gap: How a Specialized Heart Failure Program Improves Guideline-Directed Medical Therapy Optimization for Rural Patients
Authors: Velasco Claudia Mae , Baksh Gladys , Reesor Heather , Haydo Michele , Ali Omaima
Published: November 2024

Background:
Previous research has shown that patients with heart failure with reduced ejection fraction (HFrEF) living in rural areas have suboptimal utilization of guideline-directed medical therapy (GDMT). Considering the associated increased mortality risk, this highlights the need for novel approaches to improve GDMT optimization for rural patients. The aim of this study was to evaluate how rural residence influences outcomes in a multidisciplinary, telehealth-based HF-GDMT optimization program implemented at our institution.

Methods:
We studied 322 patients who participated in a HF-GDMT optimization program led by a HF nurse practitioner and clinical pharmacist at Penn State Hershey Medical Center. We categorized residence at the time of enrollment using the Rural-Urban Commuting Area (RUCA) classification system. Differences in patient characteristics and program outcomes between the two groups were analyzed. P < 0.05 indicated statistical significance.

Results:
Among the 322 patients enrolled, 56 (17.4%) resided in rural areas and 266 (82.6%) in urban areas. Rural patients were younger (mean age 61.1 vs. 65.1; p=0.04) and the two groups differed significantly in racial demographics (p=0.006). The rural group had a higher proportion of patients with chronic HF (55.4% vs. 39.8%; p=0.038) and fewer patients with a recent HF hospitalization (30.4% vs. 49.2%; p=0.012). As far as outcomes, program completion rates were similar between rural and urban patients (83.9% vs. 83.1%; p=1). Those who received target doses of the four GDMT drug classes versus the maximum tolerated dose were also similar between the rural and urban groups (21.4% vs. 15.8%; p=0.32).

Conclusions:
Patients from rural areas were more likely to present with chronic HF and less likely to have recent HF hospitalizations compared to their urban counterparts, suggesting potential disparities in access to HF care. Despite these differences, program outcomes, measured by completion rates and GDMT medication titration, were comparable between the two groups. Our findings emphasize the crucial role of specialized HF programs in advancing GDMT use for rural patients, which may ultimately improve HF outcomes and bridge the healthcare gap.
Abstract 4135741: Perioperative and Long-term Impact of Contemporary Optimal Guideline-Directed Medical Therapy in Patients with Reduced Ejection Fraction Undergoing Aortic Valve Surgery for Pure Severe Chronic Aortic Regurgitation
Authors: Cinq-Mars Alexandre , Blais Marie-Christine , St-Louis Roxanne , PUJOS Charline-Hélyette , Massot Montse , Veillette Jean-Benoît , Bernier Florence , Turgeon Pierre Yves , Belzile David , Bernier Mathieu , Dagenais Francois , Senechal Mario
Published: November 2024

Background:
Although recent studies have showed improved outcomes, aortic valve replacement (AVR) for chronic aortic regurgitation (AR) in the presence of reduced left ventricular ejection fraction (LVEF) is associated with a higher surgical risk. Contemporary long-term outcome remains poorly investigated.

Methods:
Between January 2004 and August 2019, we identified 122 patients who underwent AVR for pure chronic severe AR with LVEF less than 50%. Patients with severe reduced LVEF (<35%, n=37) were compared with those with mild to moderate reduced LVEF (35% to 50%, n=85).

Results:
Preoperative and intraoperative characteristics were similar in both groups. Operative mortality for the entire cohort was 1,6% (n=2) and similar across the LVEF spectrum. Postoperative intra-aortic balloon pump has been used in 2/37 patients with LVEF < 35% compared to 0/85 patients with LVEF 35-50% (p = 0.09). Patients with severely reduced LVEF had a longer length of stay (10.1±5.5 vs 7.8±3.5 days, p=0,02) while the rate of stroke, atrial fibrillation, acute renal failure, and pulmonary infection were similar between groups. Postoperatively, optimal medical therapy was achieved in most patients and more than a quarter of patients with LVEF < 35% benefited from cardiac resynchronization therapy. At the latest follow-up, mean LVEF was 42±12% in the severe reduced LVEF (vs. baseline 28±6%, p<0.001) and 51±9% in the mild to moderate reduced LVEF group (vs. baseline 45±4%, p<0.001). Freedom from cardiovascular (CV) death at ten years was 87.2% in the severe reduced LVEF group and 94.7% in patients with mild to moderate reduced LVEF (p=0.10). Freedom from heart failure (HF) hospitalization at ten years was higher in the mild to moderate reduced LVEF group (96.3%) than in the severely reduced LVEF group (88.3%) (p=0.009).

Conclusion:
In this contemporary cohort of patients undergoing AVR for chronic severe AR, patients with severely reduced EF treated with optimal guideline-directed medical therapy had a similar operative mortality and freedom from CV death than patients with mild to moderate reduced LVEF. Favorable left ventricular remodeling was observed in both groups at 1 year follow-up. Hospitalization for HF was low with less than 15% in both groups at 10 years follow-up; although rehospitalisation occurred more frequently in severe reduced LVEF group.
Abstract 4135790: Carotid Plaque Inflammation Is Associated with Atrial Fibrillation
Authors: Nardi Valentina , Di Venanzio Ludovica , Mahmoudi Hamidabad Negin , Copley Elizabeth , Tiwari Ani , Rajotia Arush , Lutgens Esther , Lerman Lilach , Lerman Amir
Published: November 2024

Introduction:
Atrial fibrillation (AF) is prevalent in patients with atherosclerotic coronary and carotid artery disease and is associated with elevated plasma inflammatory markers, such as Interleukin (IL)-6. In carotid artery atherosclerosis, macrophages are considered a local marker of inflammation.

Hypothesis:
We hypothesize that AF is independently associated with carotid plaque inflammation.

Aims:
In patients undergoing carotid endarterectomy (CEA), we aimed to determine whether carotid plaques inflammation is associated with AF.

Approach:
In this prospective cohort study, consecutive patients with carotid artery disease undergoing CEA were enrolled. From the plaques removed during surgery, fixed in formalin and embedded in paraffin blocks, sections were stained with antibodies against CD68 to detect macrophages
(Fig.1A)
. Digital copies of the slides were created by Motic Easy Scan and histologically annotated with QuPath. The percentage of CD68+ cells was defined as (CD68+ positive cells/total nuclei) x 100. Flash-frozen plaque segments were analyzed by ELISA for IL-6 concentration. Baseline demographics and clinical data, including AF diagnosis, were extracted from the electronic health records.

Results:
A total of 106 patients undergoing CEA, with a median age of 73 [67-78] years and comprising 83 (78.3%) males, were included in the study. AF was diagnosed prior to CEA in 13 (12.3%) patients. Univariate logistic regression showed that plaque CD68+ cell content was associated with AF (OR 1.048 [95% CI 1.010 – 1.088]; p = 0.013).

Additionally, in Mann-Whitney test IL-6 levels were significantly over twofold higher in plaques of patients with AF compared to those without AF (82.4 [64.9-111.7] pg/mg vs 37.0 [18.4-93.3] pg/mg; p=0.020)
(Fig. 1B)
.

Conclusions:
The current study demonstrates an association between carotid atherosclerotic plaque macrophage content, IL6 levels and AF, supporting the role of inflammation in the pathogenesis of AF in these patients. Further studies are needed to determine the potential of plaque inflammation as a therapeutic target in AF.
Abstract 4136030: Fatty acids disturb cardiomyocyte proliferation by increasing PDK4 and HMGCS2 via PPARδ activation
Authors: Tanaka Shota , Hirota Akane , Okada Yoshiaki , Obana Masanori , Fujio Yasushi
Published: November 2024

Background:
Almost all cardiac diseases are difficult to cure entirely because cardiomyocytes rarely proliferate to recover cardiac damage. In fact, most mammals have a capacity to regenerate cardiomyocytes immediately after birth. Newborn infant drastically changes cardiac metabolism from glycolysis to oxidative phosphorylation using fatty acids. Previous research revealed that lipid metabolism had a negative influence on cardiomyocyte cell cycle but the mechanism has not been clarified completely.

Objective:
This study was performed to elucidate the way fatty acid metabolism affects cardiomyocyte proliferation.

Methods and results:
Isolated and cultured neonatal rat cardiomyocytes (NRCM) were treated with the mixture of palmitic acid, oleic acid, and L-carnitine (FA mix) for 24 hours. Realtime RT-PCR revealed that FA mix increased the mRNA expressions of pyruvate dehydrogenase kinase 4 (PDK4), a fatty acid metabolism regulator, and HMG-CoA synthase 2 (HMGCS2), a ketogenic factor, as well as β-oxidation-related enzymes in dose dependent manner. Simultaneously, the results of immunofluorescent staining showed that FA mix decreased cardiomyocytes expressing Ki67, a cell cycle marker. GW501516, a peroxisome proliferator-activated receptor δ (PPARδ) agonist, also increased fatty acid metabolism factors with the reduction of Ki67 positive cardiomyocytes, whereas fenofibrate, a PPARα agonist, or pioglitazone, a PPARγ agonist, caused little or no change in these phenotypes. Moreover, NRCM pretreated with GSK3787, a PPARδ antagonist, before FA mix stimulation suppressed the upregulations of fatty acid metabolism factors and the reduction of Ki67 expressing cardiomyocytes. Finally, the lentiviral vectors which expressed PDK4 or HMGCS2 were produced to investigate these proteins suppressed NRCM cell cycle directly. Either overexpressing PDK4 or HMGCS2 decreased Ki67 positive NRCM without the upregulation of each other or β-oxidation-related enzymes.

Conclusion:
Fatty acids disturbed NRCM proliferation by upregulating PDK4 and HMGCS2 through the activation of PPARδ independently from β-oxidation.
Abstract 4136136: Left Ventricular Global Longitudinal Strain: An Imaging Marker Associated with Improved Survival in Paradoxical Low-Flow, Low-Gradient Severe Aortic Stenosis
Authors: Dahan Shani , Tran Nathanael , Kang Jagdip , Dal-Bianco Jacob , Hung Judy
Published: November 2024

Background:
The optimal clinical management and timing of intervention are less well defined in paradoxical low-flow, low-gradient severe aortic stenosis (PLFLG AS). Left ventricular global longitudinal strain (LV-GLS) has been shown to predict outcomes in high flow severe AS, but there is lack of data in patients with PLFLG AS. Given the exaggerated LV hypertrophy and remodeling pattern in PLFLG AS, LV-GLS may be a mechanistic imaging marker for worse outcomes.

Hypothesis:
In patients with PLFLG AS, LV-GLS is associated with adverse clinical outcomes by detecting subclinical myocardial fibrosis resulting from myocardial remodeling due to LV pressure overload.

Methods:
We examined patients with PLFLG AS defined as AVA <1cm
2
, mean gradient <40mmHg and preserved left ventricular ejection fraction (LVEF) ≥50%, with low-flow state defined as transvalvular flow rate (Q) ≤210 ml/sec. Exclusion criteria included moderate or greater mitral or aortic regurgitation and presence of atrial fibrillation at the time of echocardiogram. LV strain analysis was performed using 2D-strain imaging software (TomTec, Chicago, IL). Clinical outcome data were obtained via the electronic health record. The primary outcome was defined as all-cause mortality. Patients were stratified by LV-GLS above and below the median value.

Results:
A total of 198 patients were included in the analysis, with a median LV-GLS of -12.3% [IQR: (-9.8,-16.3)]. Over a median follow-up time of 1.2 years, 130 deaths (65.6%) were identified. Patients with less negative LV-GLS (n=101) had worse survival than those with more negative LV-GLS (n=97; 22 vs 38%; p=0.02) (Fig 1). After multivariable adjustment for potential confounders (stroke volume index, aortic valve mean gradient, relative wall thickness, age, sex, heart failure, hypertension, coronary artery disease, and diabetes), less negative LV-GLS was independently associated with adverse outcomes (HR 1.56; 95% CI (1.03-2.38); p=0.04).

Conclusions:
In patients with PLFLG AS as defined by a transvalvular flow rate (Q) ≤210 ml/sec, reduced LV-GLS is associated with increased all-cause mortality. LV-GLS may serve as an imaging marker to help guide clinical decision making in PLFLG AS.
Abstract 4136210: Meta-Analysis of Efficacy and Safety in DAPT De-escalation: Transitioning from Ticagrelor to Clopidogrel in Acute Myocardial Infarction Following Percutaneous Coronary Intervention at twelve-Month Follow-Up
Authors: Hashim Hashim Talib , Alhatemi Ahmed Qasim Mohammed , Riaz Sania , Ali Zahraa Hussein , Rifai Mohamed K , Saeed Humza , Tabassum Shehroze , Sulaiman Fatimah Abdullah , Al-Obaidi Ahmed Dheyaa , Saab Omar
Published: November 2024

Background:
In the management of acute myocardial infarction (AMI) following percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) plays a crucial role in preventing recurrent ischemic events. Recent studies have explored the feasibility and safety of de-escalating DAPT from ticagrelor to clopidogrel.

Methods:
We conducted a systematic review and meta-analysis by searching several databases, including Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, MEDLINE (including MEDLINE InProcess) (OvidSP), Web of Science, Embase (OvidSP), and Scopus. We assessed the risk of bias using the ROB2 Cochrane tools for randomized controlled trials (RCTs). The analysis was performed using RevMan Cochrane software.

Results:
A total of ten studies including observational and clinical studies involving N=18,001patients (11,458 de-escalated from ticagrelor to clopidogrel after 12 months and 6,543 remained on ticagrelor after 12 months post-PCI) were included. There was no difference in the risk of all-cause death (RR 0.98; 95% CI 0.69 to 1.38; p=0.90), cardiovascular death (RR 1.09; 95% CI 0.68 to 1.74; p=0.73), myocardial infarction (RR 0.90; 95% CI 0.71 to 1.14; p=0.37) and stroke (RR 0.81; 95% CI 0.50 to 1.32; p=0.41) between the two groups.

Conclusion:
In conclusion, transitioning from ticagrelor to clopidogrel in acute myocardial infarction following percutaneous coronary intervention appears to be a feasible strategy for de-escalating dual antiplatelet therapy (DAPT). While maintaining efficacy in preventing adverse cardiovascular events, such as stent thrombosis, this approach may mitigate bleeding risks associated with prolonged ticagrelor use.
Abstract 4136274: A Case of Myocardial Infarction with Non-obstructive Coronary Arteries (MINOCA) Complicated by a Ventricular Septal Defect (VSD)
Authors: Thai Theresa , Lipinski Jerry , Sola Michael , El Rafei Abdelghani , Desai Aken , Sailer Christine
Published: November 2024

Case:
A 69-year-old woman with a history of hypertension and tobacco use disorder presented with acute chest pain. The patient was found to have classic anterior ST elevation myocardial infarction (STEMI) pattern on electrocardiogram (ECG) with high-sensitivity troponin of 12,772 ng/L and was taken emergently to the catheterization laboratory. Coronary angiography showed tortuous coronary vessels though without evidence of obstructive coronary artery disease, plaque rupture, ulceration, dissection, or vasospasm. Transthoracic echocardiogram showed an apical ventricular septal defect (VSD) with normal left ventricular systolic function of 60%. Cardiac computed tomography (CT), confirmed a discrete apical VSD that was 7.93 mm in diameter and multiple small VSDs distally in the septum. Right heart catheterization revealed severe left-to-right shunting with a ratio of pulmonary blood flow to systemic blood flow (Qp:Qs) of 2.8.

Early surgical repair of the apical VSD was pursued despite known high operative risk given the hemodynamic significance of the shunt. The patient developed ongoing hemodynamic instability from cardiogenic shock with inability to ween from intra-aortic balloon pump (IABP). Unfortunately, because of the location of the residual VSDs and elevated panel-reactive antibody testing of 98%, the patient was deemed to not be a candidate for percutaneous closure or heart transplantation, respectively.

Discussion:
An acquired ventricular septal defect (VSD) is a rare and catastrophic complication of myocardial infarction, typically with a culprit obstructive coronary artery lesion identified on coronary angiography. Acquired VSDs in myocardial infarction with nonobstructive coronary arteries (MINOCA) is an even more rare phenomenon. Possible causes include low flow, inflammation, intimal disruption, or vasospasm of coronary arteries. Our case highlights that MINOCA can present with life-threatening complications similar to obstructive STEMI.

The timing of intervention and treatment approach of acquired VSDs remains an area of debate. The life-threatening effects of VSDs make it critical to manage in a multidisciplinary manner involving advanced imagers, interventional cardiologists, cardiothoracic surgeons, and heart failure specialists. This case emphasizes the importance of maintaining a high index of suspicion for abnormal coronary anatomy, even in patients with MINOCA, and prompt interdisciplinary decision making to reduce mortality.
Abstract 4136280: Inflammation and Cancer Mortality among CVD Individuals: NHANES-Continuous study
Authors: Elsayed Omar , Okwuosa Tochi , Addison Daniel , Cortes Jorge , Dent Susan , Al-Kindi Sadeer , Hedrick Catherine , Weintraub Neal , Wang Xiaoling , Guha Avirup
Published: November 2024

Background:
Both cancer and cardiovascular disease (CVD) are the leading causes of death worldwide. While previous research showed a relationship between CVD and cancer incidence, limited evidence is available regarding the relationship between inflammation and cancer mortality in CVD patients.

Methods:
A prospective cohort study using data from the continuous National Health and Nutrition Examination Survey (NHANES) (1999-2016) merged with Medicare and National Death Index (NDI) mortality data until December 31, 2018. We included CVD individuals with no history of cancer at baseline to investigate the relationship between inflammatory markers, including Neutrophil-to-Lymphocyte ratio (NLR), as the main exposure and cancer mortality as the main outcome.

Results:
We included 4,089 adult individuals representing 127,809,316 individuals (47% females, 72% non-Hispanic Whites, and 5% Hispanics). The risk factor analysis (Table) using the competing risk modeling showed that while inflammatory markers did not show significant associations with cancer mortality in the overall analysis, upon stratification by race/ethnicity, NH-Blacks showed higher cancer mortality with higher WBC count (aHR 5.61, 95% CI 1.66-18.91, p=0.007) and NLR (aHR 2.97, 95% CI 1.19-7.42, p=0.02), but lower cancer mortality with higher neutrophil (aHR 0.08, 95% CI 0.01-0.60, p=0.02) and lymphocyte (aHR 0.34, 95% CI 0.15-0.80, p=0.02) counts. Notably, our NH-Blacks showed lower neutrophils at baseline than others which could be explained by a phenomenon called “Benign Ethnic Neutropenia -BEN-” that still brings more complexity when interpreting NLR.

Conclusions:
Our study highlights the close relationship between cardiovascular health, inflammation, and cancer mortality. The findings also suggest that race/ethnicity may play a significant role in the relationship between inflammation and cancer mortality among individuals with CVD. Yet, further research is still needed to underpin the biological pathways influencing this relationship.
Abstract 4136294: Carbohydrate intakes and cardiovascular disease risk factors in South Asians: Results from 56,024 participants in Bangladesh, India, Pakistan, and Sri Lanka
Authors: Lahiri Anwesha , Imamura Fumiaki , Kasturiratne Anuradhani , Jha Vinitaa , Katulanda Prasad , Khawaja Khadija , Mridha Malay , Anjana Ranjit Mohan , Chambers John , Forouhi Nita
Published: November 2024

Background:
Evidence on effects of carbohydrate intake with cardiovascular disease risk factors is inconsistent and has limited generalizability to diverse populations such as South Asians, whose carbohydrate intakes are typically high.

Aims:
We examined the association of the quantity and types of carbohydrate intake with two risk factors for major cardiovascular events– hypertension (HT) and hypercholesterolemia (HC).

Methods:
We analyzed cross-sectional data from participants aged ≥18 years in the South Asia Biobank in Bangladesh, India, Pakistan, and Sri Lanka. Using dietary data assessed with interviewer-led 24h diet recalls, we calculated intakes of total and subtypes of carbohydrates and several indices of carbohydrate quality. Primary outcomes were HT and HC, defined by medication use, doctor diagnosis, blood pressure and blood lipid levels. With mixed effects Poisson regression, HT and HC was regressed on quantiles of carbohydrate intakes by country to estimate prevalence ratios (PR) and 95% confidence intervals (CI), followed by meta-analysis pooling country-specific estimates. We examined interactions by diabetes status and adiposity.

Results:
Of 56,024 adults, 36.6% had HT, 16.1% had HC. In pooled multivariable analyses comparing extreme quantiles, total carbohydrate intake was not associated with HT or HC prevalence. Fructose, free sugar and free sugar-to-fiber ratio were associated with higher prevalence of HT (PRs
Q5vsQ1
: 1.03-1.15). Higher intakes of cereal fiber (PR
Q4vsQ1
: 0.96, 95% CI: 0.95-0.98) and legume fiber (PR
Q4vsQ1
: 0.98, 95% CI: 0.97-0.98) were associated with lower prevalence of HT and higher cereal fiber intake with lower HC prevalence (PR
Q5vsQ1
: 0.80, 95% CI: 0.75-0.85). Diabetes and adiposity were observed as effect-modifiers (p<0.001). There were null associations in adults with diabetes but in non-diabetic adults, free sugar intake was related positively with HT (PR
Q5vsQ1
: 1.07, 95% CI: 1.05-1.09) while fiber intake was inversely related (PR
Q5vsQ1
: 0.98, 0.95-0.97). Starch, sugar and free sugar intake were associated positively with HT prevalence in adults with high body fat (≥20% for men; ≥30% for women) and visceral fat (≥10%) levels (PRs
Q5vsQ1
: 1.03-1.20); associations were null for low body and visceral fat levels. Associations varied by country (between-country heterogeneity I
2
>60%).

Conclusion:
Associations of dietary carbohydrates with HT and HC depended on the quality and type of intake in South Asians.
Abstract 4136316: BMP10 as novel marker for right atrial dilatation and pressure in precapillary pulmonary hypertension
Authors: Llucia-Valldeperas Aida , Van Wezenbeek Jessie , Groeneveldt Joanne , Sanchez-Duffhues Gonzalo , Vonk Noordegraaf Anton , Bogaard Harm , Goumans Marie Jose , De Man Frances
Published: November 2024

Introduction:
Precapillary pulmonary hypertension (precPH) leads to increased right atrial (RA) stretch and pressure. The right atrium is the major source of bone morphogenetic protein 10 (BMP10) in adults.

Aim:
This study aims to investigate BMP10 in relation to RA dilatation and pressure overload.

Methods:
We studied
BMP10
mRNA in fresh RA tissue of N=5 Chronic Thromboembolic Pulmonary Hypertension (CTEPH) patients and N=9 controls and protein expression in paraffin-embedded RA tissue of N=4 Pulmonary Arterial Hypertension (PAH) patients and N=6 controls. We prospectively included 48 precPH patients (N=22 idiopathic PAH, N=14 hereditary PAH and N=12 CTEPH, and N=16 controls. To study BMP10-induced transcriptional activity, we assayed serum samples in human microvascular endothelial cells (HMEC) with a BMP-responsive transcriptional luciferase assay. BMP10 activity was calculated by subtracting BMP activity after incubation with antibodies for Alk1Fc and bone morphogenetic protein 9 (BMP9). We assessed correlations between BMP10 activity and RA dilatation (RA max volume>79 ml/m
2
for male or >69 ml/m
2
for female) and right ventricular (RV) dilatation (RV end-diastolic volume>108 ml/m
2
for male and >96 ml/m
2
for female). In a cohort of CTEPH patients that underwent pulmonary endarterectomy (PEA) we assessed the effect of pressure unloading on BMP10 activity. Normality of data was checked and statistical differences between groups were tested using an independent sample t-test or Wilcoxon rank-sum test.

Results:
BMP10
mRNA, protein and downstream activity were higher in the precPH RA tissue (Figure 1A-F). High systemic BMP10 activity was associated with RA dilatation and high RA pressure, but not RV dilatation in precPH (Figure 2A-C). Finally, pressure unloading after PEA in CTEPH patients results in a reduction in BMP10 activity (figure 2D).

Conclusions:
Local RA BMP10 expression and activity is increased in precPH. Increased systemic BMP10 activity was related to RA dilatation and pressure. Pressure unloading of the right heart leads to a reduction of systemic BMP10 activity. Future studies are needed to determine whether increased BMP10 release is an adaptative mechanism or can be used as therapeutic target.
Abstract 4136394: Elucidation of a novel genetic substrate responsible for genetically elusive ring-like arrhythmogenic cardiomyopathy
Authors: Tester David , Castrichini Matteo , Ackerman Michael , Giudicessi John
Published: November 2024

Background:
Arrhythmogenic cardiomyopathy (ACM) is a genetic heart disease characterized by fibrofatty replacement of ventricular myocardium. Arrhythmogenic left ventricular (LV) cardiomyopathy (ALVC) is a phenotypic variant of ACM predominantly involving the LV. Mutations in genes encoding for desmosome proteins and filamin C have been implicated in ALVC, especially in the setting of a ring-like late gadolinium enhancement (LGE) imaging pattern.

Objective:
To identify the underlying genetic substrate responsible for genetically elusive ring-like ALVC in a patient with seemingly sporadic/recessive disease.

Methods:
A 38-year-old male was referred for genetic investigation to determine the underlying genetic substrate responsible for his ALVC phenotype. The patient fulfilled both electrocardiographic (low voltage in the limb leads and anterolateral T-wave inversions) and imaging (>1 segment of subepicardial LGE) criteria for ALVC. Additionally, the patient experienced unexplained episodes of tachycardia, shakiness, sweating, and nausea prompting concern for an underlying neuromuscular disease. Genome sequencing (GS) was performed on DNA isolated from the affected patient and both of his unaffected parents. Variants were filtered assuming either a sporadic de novo occurrence or an autosomal recessive inheritance pattern.

Results:
GS identified compound heterozygous GNPTAB variants in the affected patient. A previously reported maternally derived p.Leu257Leu (c.771G>A) variant involving the last nucleotide of exon 7 of the
GNPTAB
gene and a novel paternally inherited Lys834fs*5 frame-shift variant were identified. The p.Leu257Leu variant has been reported to cause aberrant splicing and exon skipping of the GNPTAB mRNA transcript. Pathogenic variants in the
GNPTAB
encoded N-acetylglucosamine-1 (GlcNAc)-phosphotransferase subunits alpha/beta cause mucolipidosis type III, a rare recessive lysosomal storage disease characterized by coarse facial features, developmental delay, short stature, skeletal deformities, and cardiac involvement including valvular thickening and cardiomyopathy.

Conclusions:
Here, using a genome sequencing trio analysis we identified a compound heterozygous GNPTAB pathogenic variants as the underlying genetic substrate in a patient with ring-like ALVC and concomitant neuromuscular disease manifestation. Genome sequencing may identify the genetic etiology responsible for an otherwise undifferentiated diagnosis of cardiomyopathy.
Abstract 4136403: Impact of Coronary Artery Calcium Scores on Cardiovascular Risk and Preventive Therapies: A Systematic Review and Meta-Analysis
Authors: Bedi Angad , Al Hennawi Hussam , Khan Muhammad Khuzzaim , Tabassum Shehroze , Ramirez Rachel , Watson Robert
Published: November 2024

Introduction:
Coronary artery calcium (CAC) serves as a key marker of atherosclerosis and is widely utilized in the noninvasive evaluation of coronary artery disease. We aim to compare cardiovascular risk outcomes and the likelihood of initiating or continuing pharmacological and lifestyle preventive therapies in asymptomatic and symptomatic patients with a CAC score greater than zero and those with a CAC score of zero with no established diagnosis of coronary artery disease.

Methods:
We performed systematic searches of PubMed, Scopus, Google Scholar, Cochrane Central, and ClinicalTrials.gov from inception to May 2024. Our search focused on randomized controlled trials and observational studies comparing outcomes between patients with a CAC score greater than zero and those with a CAC score of zero.

Results:
We included 53 observational studies, incorporating data from 210,672 asymptomatic and 32,477 symptomatic patients. Over a mean follow-up duration of 8.6 years, we observed that a CAC score greater than zero significantly correlated with an elevated risk of major adverse cardiovascular events (MACE) (OR: 5.58; 95% CI: 4.05–7.69; P < 0.00001). This association extended to all-cause mortality (OR: 3.90; 95% CI: 2.78–5.48; P < 0.00001), myocardial infarction (OR: 4.01; 95% CI: 3.45–4.65; P < 0.00001), and the need for revascularization (OR: 11.90; 95% CI: 6.82–20.78; P < 0.00001). Patients with a CAC score greater than zero were more likely to commence and continue aspirin therapy (OR: 2.45; 95% CI: 1.56–3.83; P < 0.0001 for initiation and OR: 1.71; 95% CI: 1.31–2.23; P < 0.0001 for continuation). Similar trends were noted for lipid-lowering medications (OR: 2.44; 95% CI: 1.57–3.79; P < 0.0001 for initiation and OR: 2.48; 95% CI: 1.53–4.01; P = 0.0002 for continuation), as well as the initiation of blood pressure medications (OR: 1.94; 95% CI: 1.61–2.33; P < 0.00001). Furthermore, a CAC score greater than zero was linked to increased adoption of lifestyle modifications, including enhanced physical activity (OR: 1.84; 95% CI: 1.41–2.41; P < 0.00001) and dietary changes (OR: 1.94; 95% CI: 1.52–2.49; P < 0.00001).

Conclusion:
Patients with elevated CAC scores are more likely to initiate and continue preventive pharmacological therapies and adopt beneficial lifestyle modifications. These findings underscore the importance of CAC scoring in guiding the management and prevention of cardiovascular disease in both asymptomatic and symptomatic populations.