bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4144103: Circulating miRNAs are Differentially Expressed in Pediatric Dilated Cardiomyopathy Patients with Favorable vs. Poor Outcomes
Authors: Stuart Scott , Miyamoto Shelley , Lipshultz Steven , Hernandez Ana Laura , Hamza Taye , Wilkinson James , Karimpour-Fard Anis , Colan Steven , Sucharov Carmen
Published: November 2024

Introduction:
microRNAs (miRs) are small single stranded RNAs capable of targeting expression of several genes. Circulating miRs can be important biomarkers of disease progression. Children with dilated cardiomyopathy (DCM) experience multiple outcomes including recovered-normalization, stable disease, and progression to death/ need for transplant. We hypothesized that circulating miRs are differentially expressed among these cohorts and may serve as useful prognostic biomarkers in pediatric DCM patients.

Methods:
RNA-sequencing was used to detect and quantify circulating miRs. Samples were collected within 3 months of a new diagnosis of DCM. Inclusion criteria included <18 years of age at diagnosis of idiopathic or familial DCM (LVEF<50% or left ventricular end-diastolic dimension [LVEDd] z-score ≥+2). Primary outcomes within 1 year of enrollment were defined as: [1] Death, cardiac transplant, or initiation of mechanical circulatory support; [2] Recovered-normalization of LVsize and function (LVEF≥50% and LVEDd z-score <+2) or [3] Stable-persistent DCM with LVEF<50% or LVEDd z-score ≥+2. Statistical analysis included random forest and hierarchical clustering (HC).

Results:
Sequencing was performed on 76 patients: death/transplant (n=35), recovered (n=20), or stable DCM (n=21). The top three differentially expressed miRs between the death/transplant and recovery group were miR-424-5p, miR-335-5p, and miR-503-5p (Figure A). HC based on expression of these 3 miRs identified an expression pattern associated with death/transplant outcome (Figure B). miR-503-5p was also among the top 3 miRs most differentially expressed between the stable and the recovery group.

Conclusions:
These results indicate circulating miRs can predict recovery in the pediatric DCM population. Importantly, miR-503-5p was more highly expressed in the recovery group when compared to both the stable and transplant groups, suggesting expression of this miR may be associated with favorable outcomes. A unique biomarker signature of miRs specific to children with DCM who have the potential to recover would improve risk stratification of this population.
Abstract 4144107: ApoB-100 peptide nanoparticles inhibit established atherosclerosis progression in female HLA-A*0201 transgenic mice
Authors: Zhou Jianchang , Zhao Xiaoning , Dimayuga Paul , Lio Nicole , Cercek Bojan , Trac Noah , Chung Eun Ji , Shah Prediman , Chyu Kuang-Yuh
Published: November 2024

Background:
Sex, cholesterol and immune responses play significant roles in atherosclerosis development. Cholesterol lowering and global anti-inflammatory therapy have therapeutic limitations. Immune modulation with ApoB-100 peptide-based nanoparticles, named P210-PAM, reduced atherosclerosis in ApoE
–/–
mice carrying human
HLA-A*0201
allele (
A2Kb-Tg)
when administered before significant atherosclerosis formed. In this study, we investigated the potential interaction among sex, cholesterol and immune responses in modulating atherosclerosis with P210-PAM therapy.

Methods:
A2Kb-Tg
mice of both sexes fed high fat diet for 8 weeks were injected s.q. 3x with P210-PAM at 2–3-week intervals with or without change to normal chow at the second injection time point. PBS injections served as controls. Aortic atherosclerosis, splenic monocyte/macrophage and T cells were evaluated.

Results:
P210-PAM therapy without diet change had no effect on established atherosclerosis in both sexes (Table). P210-PAM therapy in female mice with diet change significantly inhibited growth of established atherosclerosis (Table) and reduced IL1R1 expression on splenic monocyte/macrophages (106.1±16.9, N=12,
vs
137.5±23.6, N=13; P<0.05) with increased splenic CD8
+
T
CM
(25.6±7.8%, N=13,
vs
19.5±4.9%, N=14; P<0.05). P210-PAM therapy with diet change had no effect in male mice (Table).

Conclusion:
P210-PAM therapy with cholesterol lowering has a sex-specific effect on atherosclerosis highlighting the potential interaction among sex, cholesterol and immune responses in modulating atherosclerosis.
Abstract 4144131: High Prevalence of CAC on PET/CT in Patients Undergoing Genetic Testing for Familial Hypercholesterolemia Regardless of Genetic Result
Authors: Knight Stacey , Le Viet , Rimmasch Megan , Kamp Bailey , Iverson Leslie , Knowlton Kirk , Anderson Jeffrey
Published: November 2024

Introduction:
Recently it was published that 40-50% of genetic positive familial hypercholesterolemia (FH) patients will have zero coronary artery calcium (CAC). However, it is unclear if this rate is similar to patients who met indications for FH genetic testing but had a negative genetic result. We tested the hypothesis that the presence of CAC will be similar for these 2 patient groups.

Methods:
All patients undergoing genetic testing for FH from July 2016 to Jan 2024 (n=332) that also had a cardiac positron emission tomography-computed tomography (PET/CT) stress test (n=101) were studied. The presence of CAC was determined for these patients using the low-dose attenuated correction CT images. We further examined CAC severity for those with an Agatston CAC score (n=53) or with a report of CAC severity based on the low-dose attenuated correction CT (n=18). Fisher exact tests and Wilcoxon rank sum tests were used for the comparisons.

Results:
Of patients undergoing FH testing (n=332), average age was 49±19 years, 51% were male, and 89% white. For those who had a PET/CT (n=101), the average age at time of FH testing was 57±13y, 59% were male, and 87% white. Patients who underwent PET/CT were less likely to have a positive genetic test (14%) compared to those without a PET/CT (27%) (p=0.006). The CAC, other PET/CT results and conclusions by the reading cardiologist, and maximum low-density lipoprotein cholesterol (LDL-C) are shown in the table. A large percentage of both positive (93%) and negative (84%) FH genetic tested patients had CAC present. The presence and severity of the CAC was not significantly different between these 2 groups. Other PET/CT results were also similar for the FH positive and negative genetic test groups. However, those with genetically confirmed FH had significantly higher maximum LDL-C than those with a negative result (p=0.006) and a higher LDL-C closest to the time of PET/CT (p=0.02).

Conclusion:
While this is a small study of selected FH tested patients with PET/CT, we found nearly all of the genetically confirmed FH patients that had a PET/CT, had CAC. Those with genetically confirmed FH had almost double the LDL-C values compared to patients that tested negative for FH on genetic testing. However, this did not result in significantly higher rates or more severe CAC scores or higher risk assessment on PET/CT.
Abstract 4144133: Racial And Ethnic Disparities In Outcomes Of St Segment Elevated Myocardial Infarction With Percutaneous Coronary Intervention
Authors: Ajenaghughrure Godbless , Rahima Kenan , Shemisa Kamal , MISHRA AAVASH , Kishore Gehna , Jaafar Nadim
Published: November 2024

Background:
Racial disparities in healthcare are a persistent and troubling issue, with profound implications for patient outcomes and societal well-being. Despite advances in medical science, studies consistently show that minority patients, particularly African Americans and Hispanics, face higher rates of STEMI incidence, delayed treatment, and poorer outcomes compared to their white counterparts.

Methods:
we examined the national inpatient sample 2017-2020 for adult admitted with st segment myocardial infarction,we compared the clincal outcome of patients admitted with stemi with pci based on racial distribution.STATA 18th edition was used for analyses. Age, gender, race, hypertension, diabetes, obesity, dyslipidemia, and Elixhauser comorbidity index were identified as confounders by univariate analyses and tested further with multivariate logistic regression models. The primary outcome was mortality. Secondary outcomes were the need for intubation, cardiac arrest, length of stay (LOS), and total hospital charges.

Results:
There were 582420 hospitalizations with STEMI with PCI. Mean age was 62 yrs and 71% were male. Among the admitted patients, Caucasians were 425064 (66.1%), Blacks were 47635(8.2%),Hispanics were 47555(8.2%), Asians were 16004(2.8%). . All-cause mortality in patients admitted with STEMI with PCI were 34090 where subgroup Analysis with Caucasians, Blacks ,Hispanics and Asians had 23700 (5.6%) vs 32870 (6%) vs 2915(6.1%) and 1155(7.2%) respectively.

Further subgroups analysis revealed that Asians (10.8%, aOR 1.77 CI 1.54-2.03,P value<0.001) were more likely to require intubation,followed by Hispanics(10.1% aOR 1.46 CI 1.33-1.6, p value <0.001) ,then Blacks (9.4% aOR 1.2,CI 1.09-1.32 P vale <0.001)and caucasians were least likely to require intubation(7.6% )

Finally, racial subgroup showed significant primary andsecondary outcomes that are presented in Table 1.

Conclusion:
All obtained results revealed statistical significance and we considered Caucasian population as baseline. Mortality, intensive care services and resource utilization proportion was highest among Asian race followed by Hispanic race then by Black race. Understanding these disparities is essential for improving healthcare equity and ensuring that all patients receive appropriate and equitable care regardless of their racial or ethnic background.
Abstract 4144137: Discontinuation vs Continuation of Renin-Angiotensin System Inhibition Before Non-Cardiac Surgery: A Systematic Review and Meta-Analysis
Authors: Queiroz Ivo , Defante Maria Luiza Rodrigues , Barbosa Lucas , Antunes Vanio do Livramento Junior , X. Mendes Beatriz , Mazetto Roberto , Bulhoes Elisio , Silva Catarina , Romeiro Pedro , Guida Camila
Published: November 2024

Background:
The optimal management of angiotensin-converting enzyme (ACE) inhibitors during elective surgeries remains uncertain. While some studies suggest that continuing ACE inhibitors increase the risk of perioperative hypotension, others argue that discontinuation may heighten the risk of significant clinical events. This meta-analysis aims to clarify the clinical outcomes associated with continuation compared to discontinuation of ACE inhibitors in surgical settings.

Methods:
We conducted a systematic search of MEDLINE, Cochrane, and Embase for clinical trials comparing the effects of continuing versus discontinuing ACE inhibitors during surgery. Outcomes evaluated included death, stroke, myocardial injury (MI), intraoperative hypotension, postoperative hypotension, and acute kidney injury (AKI). Data were synthesized using odds ratios (OR) with 95% confidence intervals (CI). Heterogeneity was assessed with I2 statistics, and a random-effects model was applied. Statistical analyses were performed using R software version 4.3.2.

Results:
From 865 identified studies, 15 studies involving 11,519 patients met the inclusion criteria. Not all studies had outcomes available for comparison between them. The average age was 65.75 years, with 86.45% having hypertension and 13.13% with heart failure. Continuing ACE inhibitors was associated with a higher risk of intraoperative hypotension (OR 1.33; 95% CI 1.16-1.53). No significant differences were found between groups for mortality (OR 1.06; 95% CI 0.68-1.65), stroke (OR 0.99; 95% CI 0.47-2.09), MI (OR 0.98; 95% CI 0.72-1.31), postoperative hypotension (OR 1.27; 95% CI 0.74-2.17), and AKI (OR 0.88; 95% CI 0.66-1.16).

Conclusion:
Discontinuation of ACE inhibitors before non-cardiac surgery may lower the risk of intraoperative hypotension without significantly affecting mortality, stroke, MI, postoperative hypotension, or AKI. Further research with greater power and better design is needed to confirm these findings.
Abstract 4144167: Efficacy of Stem Cell Transplantation in Cardiac Regeneration and Function in Ischemic Heart Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Shivani Ravipati , Ahmad Osama , Nandipi Vibha Sri , Mathew Bejoi , MICHAEL ANITA , Vasini Vindhya , Banerjee Sumitaksha , Kaur Sakoon , Bhargav pradeep konakanchi , Baskara Salian Rishabh , Suvvari Tarun Kumar
Published: November 2024

Background:
Myocardial ischemia remains a significant global health concern for cardiovascular morbidity and mortality. In addition to the traditional treatment modalities, stem cell transplantation is emerging as a promising therapeutic intervention for cardiac regeneration and functional recovery. Our study evaluated the efficacy and clinical impact of SCT by reducing infarct scar size and improving cardiac function. The secondary objectives are to compare stem cell types, identify optimal transplantation strategies, and address safety and feasibility.

Method:
Randomized controlled trials from January 2000 to July 2023 were collected from PubMed, Cochrane, Google Scholar, and Elsevier. Based on criteria and evidence quality, screening and selection were done. A RevMan analysis was done. Infarct size, LVEF, LVESV, LVEDV, and mortality were measured. Comparator variables included placebo, medical therapy, CABG, and other types of stem cells. Randomization, allocation concealment, blinding, and therapeutic interventions differed among trials. Heterogeneity and publication bias were assessed using random-effects model and funnel plots. Sensitivity analysis and meta-regression identified outcome variability.

Results:
Seventeen studies (n = 1022 patients) met the inclusion criteria, encompassing various cell types, doses, and administration routes. Compared to controls, SCT greatly enhanced LVEF (MD: 3.39, 95% CI: 1.05 to 5.73, p = 0.005) and reduced infarct size (MD: 14.23, 95% CI: 7.12 to 21.35, p<0.0001) with an average dose of 2.03 x 107 cells/ml injected intracoronarily directly into the infarcted myocardium or the target vessel. LVESV (MD: -2.63, 95% CI: -7.99 to 2.73, p = 0.34) or LVEDV (MD: -2.00, 95% CI: -4.40 to 0.40, p = 0.10) did not improve. Differences in mortality rates were insignificant (OR: 0.71, 95% CI: 0.29 to 1.74, p = 0.46). A diverse range of patients was included, leading to moderate heterogeneity (I^2 = 52%).

Conclusion:
SCT shows potential benefits for cardiac regeneration and functional improvement. The analysis is robust, with no publication bias and mild attrition bias issues. Due to low mortality, safety was comparable to conventional therapy. These findings highlight the need for SCT strategy optimization and long-term clinical outcome studies.
Abstract 4144168: Five Years Post Heart Transplant Outcomes in Patients with Amyloidosis: A Single Center Experience
Authors: Patel Khush , Tu Zoe , Guha Ashrith , GORTHI Janardhana , Yun Allison , Krisl Jill , Kassi Mahwash , Kim Ju , Yousefzai Rayan , Ghobrial Mark , Gaber Osama , Bhimaraj Arvind
Published: November 2024

Introduction:
Many patients with amyloidosis can have advanced cardiac involvement, that drives mortality. Due to lack of definitive therapies that can reverse cardiac infiltration, cardiac replacement is the only hope for these patients. Durable left ventricular assist devices are not a good option; hence heart transplant remains mainstay. We present here long-term outcomes from a single center.

Methods:
Using EPIC Electronic Health Records’ database Clarity and UNOS center-specific report builder, we abstracted clinical information of patients who underwent a heart transplantation for cardiac amyloidosis at our center from 2004 to 2023.

Results:
Fifty-one patients underwent heart transplant for cardiac amyloidosis: 32 for Amyloid Light chain (AL) and 19 for Amyloidosis Transthyretin (TTR). Majority were males (Table 1). Of the AL transplants, 6 received concomitant kidney, 2 liver and 2 lung transplantation and of the TTR, 1 received concomitant kidney and 16 concomitant liver transplantation. There were more multi-organs in TTR compared to AL cardiac transplants (17 vs 10, p<0.001). The majority (78%) were transplanted at a higher listing status (Status 1A in older system and Status 2 in the newer system) and in the ICU at the time of transplant. Donor, baseline, and post-transplant characteristics are presented in Table 1. Five-year survival for AL cardiac transplantation was 71% compared to 92% in TTR amyloidosis with no significant difference between both (Figure 1). Majority of the causes of death were noncardiac.

Conclusion:
Select patients with end stage AL and TTR amyloidosis can successfully have prolongation of life with heart transplantation like any other etiology of end stage heart failure. Their 5 year outcomes are similar to other non-amyloid transplant patients reported in national registries.
Abstract 4144179: Cardiac Arginination Activates RIP3/CAMKII/MLKL Signaling RALBP1 Signal for ICIs-associated Myocarditis
Authors: Wang Xuejun
Published: November 2024

Background:
ICIs-induced cardiotoxicity, particularly myocarditis, poses a significant risk. This study aims to elucidate evidence of direct damage to cardiomyocytes by ICIs and explore potential molecular mechanisms for preventing ICIAM.

Methods:
Non-targeted metabolomics examined differential metabolites changes in ICIAM patients and mice. Mass spectrometry identified substrates and modification sites of the enzyme acting on aminoacyl-tRNA synthetases (ARSs). Specific acylation modification site antibody for RALBP1 were customized. The levels of endogenous and exogenous arginine acylation-modified RALBP1 were validated in cells. Immunofluorescence staining was performed to verify the degree of acylation modification. RALBP1 knockout were generated to investigate the impact of RALBP1 on cardiac function and related signaling pathways. RALBP1 deacylation modification was verified by SIRT3 knock out. RALBP1 inhibitor RBC8 validated the therapeutic effects of arginylation modification on ICIAM mice. Finally, the effect of acylation modification on RALBP1 399th lysine spot mutation (K399R) and demodification (K399A).

Results:
ICIs could induce necroptosis in cadiomyocytes through MAMs-CAMKIIδ pathways. Non-targeted metabolomics indicated arginine-related metabolism might be significant in mice and human. Meanwhile, ARSs for arginine could bind to downstream substrate RALBP1 and catalyze arginylation, which was significantly increased in ICIAM. RALBP1 knockout significantly improved cardiac function, reduced arginylation reaction, inhibition of MAM-CAMKIIδ pathway activation in ICIAM mice. SIRT3 could bind to RALBP1 to inhibit acylation reaction. Necroptosis was inhibited after arginine deacetylation modification occured. RBC8 could significantly improve mouse cardiac function and suppress necroptosis occurrence. K399A-RALBP1 exhibited a increased cardiac function after deacetylation modification and inhibited necroptosis. Conversely, K399A-RALBP1 exhibited a decreased cardiac function after increased arginylation reaction and activated necroptosis.

Conclusion:
Increased serum arginine levels increases the risk of developing myocarditis in cancer patients receiving ICIs therapy by promoting RALBP1 signaling. Inhibiting RALBP1 acylation reaction or RARS activity, suppressing MAMs-CaMKIIδ pathway activation, prevents ICIAM occurrence, highlighting the potential role of nutritional and drug interventions as a novel strategy for prevention and treatment of ICIAM.
Abstract 4144188: A Meta-Analysis of Prospective Studies Comparing Short and Longterm Outcomes of Trans-Catheter Aortic Valve Replacement in Patient with and without Cancer
Authors: Khan Muhammad Aslam , Shafique Nouman , Rahman Hammad , Aafreen Asna , Muhammad Anza , Bhatia Hitesh , Khan Abid Nawaz Khan , Akbar Usman , Khan Alamzaib , Haider Adnan , Haider Taimoor , Bhattarai Shraddha , Khan Bilal , Lamichhane Bikal
Published: November 2024

Objectives:
Trans-catheter Aortic Valve Replacement (TAVR) is the preferred treatment of choice for improving clinical outcomes in patients with Severe Aortic Stenosis. Studies published in the past in patients undergoing TAVR with cancer have shown a lower risk of short-term mortality but an increased risk of long-term mortality. This study aims to compare short-term (within 30 days) and long-term (3 years) outcomes in patients with and without a diagnosis of cancer.

Methods:
Electronic databases like MEDLINE, PUBMED, and COCHRANE library were thoroughly searched from the date of inception till May2024. 4 observational prospective studies were included in this meta-analysis. Outcomes of interest included short-term mortality (<30-day), stroke, pacemaker insertion, vascular complications, major bleeding events and long-term mortality (>3 year). The results were reported as Risk Ratio (RR) with 95% confidence intervals (CI), using a random effects model.

Results:
This meta-analysis included 6603 patients from 4 studies. Among those undergoing TAVR, individuals with cancer showed clinically significant reduction in short-term mortality (RR 0.63, 95% CI: 0.43-0.94, p = 0.02) but had higher rate of long-term mortality (RR 1.27, 95% CI: 1.15-1.42, p = 0.00001) compared to those without cancer. Additionally, more major bleeding episodes (RR of 1.17, 95% CI: 1.06- 1.29, p: 0.001) were observed in the cancer group compared to the non-cancer population. No significant difference was noted between the two groups regarding risk of Stroke (RR of 0.98, 95% CI: 0.67- 1.43, p: 0.91), pacemaker (PPM) insertion (RR 1.09, 95% CI: 0.96-1.24, p: 0.20), and Vascular site complications (RR 1.09, 95% CI: 0.95- 1.25, p: 0.20).

Conclusion:
Our study shows that cancer patients undergoing TAVR have good short-term mortality rates and comparable perioperative outcomes, but higher long-term mortality as compared to those without cancer. More randomized controlled trials are needed to further assess the long-term outcomes in this population.
Abstract 4144191: The effect of sacubitril/valsartan on epicardial adipose tissue in patients with chronic heart failure and reduced left ventricular ejection fraction
Authors: Mori Hiroki , Nakamori Shiro , Fujimoto Naoki , Mizutani Hana , Kokawa Takanori , Sato Yuichi , Goto Itaru , Ishida Masaki , Tanigawa Takashi , Sakuma Hajime , Dohi Kaoru
Published: November 2024

Background:
Natriuretic peptides (NPs) have been reported to have beneficial effects on adipose tissue, as well as the cardiovascular system and kidneys. Epicardial adipose tissue (EAT) has been recognized as an important target for the treatment of heart failure. Sacubitril/valsartan (ARNI) increases NPs by inhibiting neprilysin, but its effect on EAT has not been reported. We evaluated the impact of ARNI on EAT in patients with heart failure and compared this impact in patients with ischemic cardiomyopathy (ICM) to patients with non-ischemic cardiomyopathy (NICM).

Methods:
This study was a secondary analysis of patients enrolled in the open-label, standard treatment-controlled, randomized clinical trial (SAVE-HF) investigating the effect of ARNI in 59 stable patients with chronic heart failure and reduced left ventricular ejection fraction. Cardiovascular magnetic resonance (CMR) was performed at baseline and after 9 months. EAT was measured as the thickness of adipose tissue situated between the outer wall of the right ventricular myocardium and the visceral layer of the pericardium at a mid-ventricular level on end-diastolic short-axis cine images.

Results:
We identified 36 ICM patients and 19 NICM. There was a trend of higher prevalence of diabetes mellitus in the ICM cohort (p=0.08). Baseline EAT was similar in ICM patients (4.9 ± 1.7 mm) and NICM patients (5.1 ± 1.9 mm). In the ICM cohort, EAT was significantly reduced in the ARNI group compared with the standard treatment group (p=0.04), with an EAT reduction of 7.1%. There was an inverse relationship between the changes in EAT and atrial NP (ANP) (r=-0.39, p=0.02). After accounting for the usage of the inhibitors of the sodium-glucose cotransporter-2 receptor (SGLT2-i), the benefit of ARNI on reducing EAT remained unchanged. In contrast, ARNI was not associated with EAT reduction in the NICM cohort (p=0.9).

Conclusion:
ARNI reduced epicardial adiposity by significantly increasing circulating ANP in ICM patients, even after accounting for the usage of SGLT2-i, but it did not reduce EAT in NICM patients. These findings may suggest differential pathophysiological mechanisms of EAT adipocytes depending on the cause and pathology of heart failure.
Abstract 4144199: Safety of Discontinuing Secondary Antibiotic Prophylaxis After Echocardiographic Normalization in Early Rheumatic Heart Disease, GOAL-Post Study
Authors: Rwebembera Joselyn , Pulle Jafesi , Ndagire Emma , Okello Emmy , Engelman Daniel , Grobler Anneke , Sable Craig , Steer Andrew , Beaton Andrea
Published: November 2024

Background:
The current standard for children diagnosed with rheumatic heart disease (RHD) is secondary antibiotic prophylaxis (SAP) for at least 10 years or to a minimum age of 21. However, these recommendations were developed prior to the widespread use of echocardiography and based largely on expert opinion. A recent clinical trial in Uganda found that up to 50% of children with early RHD show echocardiographic normalization by 2 years. More research is needed to understand if continued SAP is needed after echocardiographic normalization.

Hypothesis:
There is a low risk of RHD recurrence in individuals who have had normalization of their echocardiogram following early RHD diagnosis.

Aim:
To determine the 2-year safety of not providing SAP to children and adolescents with early RHD who have shown echocardiographic normalization.

Methods:
The GOAL trial in Uganda, 2018-2021, compared SAP with Benzathine Penicillin G (BPG) to no prophylaxis among children with early RHD. GOAL-Post is a non-randomized prospective extension study of the GOAL Trial. Children with echocardiographic normalization at the end of GOAL, regardless of treatment arm, were followed prospectively without SAP, for 2 additional years. Echocardiograms were performed at the end of follow-up, uploaded to a cloud server, and interpreted by a four-person adjudication panel. Recurrence was determined by side-by-side comparison with GOAL enrollment and completion studies.

Results:
Of 345 eligible participants, 330 (96%) were enrolled, mean age 16 years (SD = 2.3), 56% female, and all completed the two-year follow-up. Only one of 330 (0.3%) progressed to moderate/severe RHD after the 2 years, and an additional 26 participants (7.9%) had evidence of mild RHD, which was clinically comparable to their cardiac status at the start of the GOAL Trial. No participants had clinical signs or symptoms of RHD and no documented rheumatic fever. This means that 99% of children and adolescents who had echocardiographic normalization were safe from moderate/severe RHD and 92% were safe from any RHD, without SAP.

Conclusion:
These findings suggest that it may be safe to consider stopping of SAP among children who show echocardiographic normalization, providing more individualized recommendations for SAP duration, rather than the current model of long-term SAP for all. Further study is needed including a stoppage of SAP trial, to generate higher quality evidence for this approach.
Abstract 4144203: "Blueberry On Top" Phenomenon. A Novel Strain Pattern In Patients With Apical Variant Hypertrophic Cardiomyopathy.
Authors: Alnaimat Saed , Mascara Mariah , Pulipati Yochitha , Madgula Anantha , Lygouris Georgios , Biederman Robert
Published: November 2024

Introduction/Background:
We have recently described “blueberry-on-top” phenomenon as a novel echocardiographic strain pattern in patients with apical variant hypertrophic cardiomyopathy (ApHCM). This so called "inverse-amyloid" pattern is identified when there is impaired peak systolic strain with paradoxically advanced time to peak strain in a hypertrophied apex with relatively spared strain in the basal segments. On a standard polar map, peak systolic strain will have a pale center while time to peak strain will depict a more robust blue center.

Research Questions/Hypothesis:
While a “blueberry-on-top” pattern has been vaguely observed in a few prior reports, its true prevalence in patients with ApHCM is currently unknown. We sought to examine the prevalence of this strain pattern among patients with ApHCM.

Methods/Approach:
A series of patients diagnosed with ApHCM, confirmed by cardiac MRI, were included. Patients with apical aneurysm, prior myocardial infarction, or aortic stenosis were excluded. All patients had a standard transthoracic echocardiogram. For uniform reporting, all echocardiogram studies were post-processed using Tomtec (Build No. 514944, Germany) which is a vendor-independent speckle tracking analysis software. Both peak longitudinal strain and time to peak strain values were exported into a standard color-coded polar map (bull's eye plot). A pixel-averaged polar map of all patients included was generated using a python script developed using an open CV library.

Results/Data:
From a cohort of 340 patients with HCM, 14 patients with ApHCM were included. Mean age was 66 years, and 50% were males. Mean LVEF was 69%. Mean scar burden by LGE quantification was 12% which is mostly localized to the hypertrophied apex. In patients who had genetic testing (n=10), half of patients had either pathogenic mutation or variant of unknown significance (VUS). About two thirds of patients had a strain pattern (inverted T waves) on EKG. Baseline characteristics are summarized in

table 1

.

A “blueberry-on-top” strain pattern was observed in 92% (n=13) of patients, while one patient had a distorted strain pattern due to apical foreshortening. A pixel-averaged polar map of all patients is shown in

figure 1

.

Conclusions:
This is the first-in-human report establishing the prevalence of “blueberry-on-top” strain pattern in a series of patients with ApHCM. This newly recognized strain pattern is unique and can be used as a supportive diagnostic feature in patients with ApHCM.
Abstract 4144244: Delineating SCAD and Non-SCAD in Acute Myocardial Infarction: Prevalence, Demographic Predictors, and Clinical Outcomes
Authors: Tan Samuel , Watanabe Atsuyuki , Trenschel Robert , Siu Wenchy , Adinugraha Paulus
Published: November 2024

Background:
Spontaneous Coronary Artery Dissection (SCAD) is an rare but increasingly recognized cause of acute myocardial infarction (AMI) traditionally thought to predominantly affect young healthy women without typical cardiac risk factors. Recent studies suggest that SCAD may be underdiagnosed, particularly among underrepresented ethnic minority groups, and that its prevalence and clinical characteristics may vary across different populations. Furthermore, gender specific differences have not yet been well explored. Contemporary population-based studies on SCAD are lacking while comparing risk factors and trends to SCAD are not well explored.

Research question:
This study aims to elucidate the trends, incidence, and risk factors associated with SCAD compared to non-SCAD acute myocardial infarction (AMI) patients. We hypothesize that there are demographic and clinical differences between SCAD and non-SCAD AMI patients

Objectives:
To describe the incidence and trends of SCAD among AMI patients.

To identify and compare risk factors for SCAD versus non-SCAD AMI.

To analyze in-hospital outcomes associated with SCAD.

Methods:
We utilized data from the Nationwide Inpatient Sample (NIS) database from January 1, 2016, to December 31, 2019, identifying patients with AMI who underwent angiography. Patients were stratified into SCAD and non-SCAD AMI groups. Multivariable logistic regression was performed to identify risk factors associated with SCAD, and in-hospital outcomes were compared between the two groups.

Results:
Out of 1,912,780 AMI patients, 0.93% were identified with SCAD. Female SCAD patients had a median age of 57 years compared to 72 years for non-SCAD females. For males, the median age was 62 years for SCAD and 67 years for non-SCAD. Older age was associated with a lower risk of SCAD, while female sex and fibromuscular dysplasia (FMD) increased the risk. SCAD patients experienced higher in-hospital mortality (5.1% vs 3.5%), more post-procedural bleeding (8.0% vs 6.6%), and greater use of mechanical circulatory support (MCS) (13.9% vs 6.2%).

Conclusion:
SCAD patients show distinct age and gender-specific risk factors compared to non-SCAD AMI patients. SCAD is associated with higher in-hospital complications, including mortality and post-procedural bleeding. Understanding these differences is crucial for improving the diagnosis and management of SCAD in diverse patient populations.
Abstract 4144255: Treatment of Human Engineered Heart Tissue with Serum from Cancer Patients with Clonal Hematopoiesis of Indeterminate Potential Cytokine Leads to Impaired Function
Authors: Kaur Harleen , Halder Saiti , Espinoza Jeacy , Chen Nathan , VanOudenhove Jennifer , Biancon Giulia , Gu Sean , Chakraborty Raja , Jain Kanika , Park Jinkyu , Qyang Yibing , Ibrahim Eiman , Halene Stephanie , Hwa John , Campbell Stuart , Jha Alokkumar , Kwan Jennifer
Published: November 2024

Introduction:
Clonal hematopoiesis of indeterminate potential (CHIP) has been shown to be an independent risk factor for heart failure and is associated with increased cardiomyopathy and mortality in cancer patients. Given that CHIP is associated with increased inflammatory cytokines, we sought to characterize the CHIP secretome in cancer patients and its impact on human engineered heart tissue (EHT) function.

Methods:
We used machine learning to identify top cytokine features associated with CHIP in a cardio oncology cohort of 173 patients. Serum from breast cancer patients who were age, co-morbidity and medication matched between CHIP and non CHIP were used in the experiments. We used human EHTs to assess whether CHIP serum treatment affects contractility and used RNA sequencing to identify significantly differentially expressed pathways. Cytokine profiling of serum samples was done using a Luminex platform for 71 human cytokines.

Results:
Machine learning identified IL-1B and CD40L as two top features of CHIP. Given DNMT3A CHIP was the most common in the cardio onc cohort, we focused on evaluating the effect of DNMT3A CHIP serum on EHT function. Compared to non CHIP serum, DNMT3A CHIP serum significantly reduced EHT contractility (p= 0.03). To evaluate whether the top cytokines identified by our machine learning model could contribute to the impairment in contractility, we co-incubated CHIP and Non-CHIP serum treated EHTs with antagonists of IL-1B or CD40L. Treatment with either IL-1B or CD40L antagonists rescued contractility defects in CHIP serum treated EHTs (p=0.015, 0.0095, respectively) but had no significant impact on non CHIP serum treated EHTs.

RNA sequencing of EHTs and pathway analysis revealed differential expression of genes and pathways in CHIP-treated and Non-CHIP serum-treated EHTs as well as in IL-1B antagonist and CD40L antagonist treated EHTs. Inflammation, metabolism pathways were top pathways differentially regulated in CHIP vs non CHIP serum treated EHTs and antagonist treatment showed modulation of these pathways.

Conclusion:
Identification of IL-1B as a top feature of CHIP is consistent with prior work. CD40L, however, has not previously been implicated in CHIP and may be more unique to cancer patients with CHIP. We show that antagonizing this pathway was able to rescue the contractility defect in CHIP serum treated EHTs, which could be another therapeutic target in patients with CHIP. The effect of other CHIP variants are underway.
Abstract 4144270: Air purification with portable air cleaners and its effect on blood pressure : An updated systematic review and meta-analysis of 21 studies.
Authors: Ramadan Shrouk , Mohamed Ahmed , Elbenawi Hossam , Afify Raneem , Desouki Mariam , Elkhayat Ibrahim , Arafa Amr Ossama Gaber , Elnady Mohamed , Mohamed Elshafey Shams Mahmoud , Elesawy Mahmoud , Abdelaziz Ahmed
Published: November 2024

Background:
Air pollution is a leading cause of cardiovascular diseases including ischemic heart disease and stroke contributing to millions of deaths, with elevated blood pressure, endothelial dysfunction, and systemic inflammation being some of the most important underlying mechanisms. Various studies showed a promising beneficial effect of indoor air purification on various health outcomes, including blood pressure. We aimed to assess the effect of indoor air purification on systolic blood pressure (SBP) and Diastolic blood pressure (DBP) and provide a rationale for home use of these filters.

Methods:
We searched PubMed, Web of Science, Cochrane and Scopus for published literature up to May 2024. We included studies that assessed air purification, including HEPA filters or electrostatic air filters, as an intervention compared to no intervention. The primary outcome of interest was mean changes in blood pressure both systolic and diastolic. Secondary outcomes were biomarkers of inflammation and oxidative stress. Mean difference (MD) and 95% CI was used in a fixed-effect model to analyze the data.

Results:
A total of 21 studies were included in our meta-analysis with a total of 1955 participants. Air purification was associated with a significant reduction in systolic blood pressure (SBP) (MD: -2.42, 95% CI: -3.42, -1.41), and diastolic blood pressure (DBP) (MD: -1.11, 95% CI: -1.76, -0.46). However, there was no significant changes in levels of inflammatory biomarkers or oxidative stress.

Conclusion: Indoor air purification was associated with significant reductions in systolic and diastolic blood pressure levels, but questions arise whether these reductions are clinically relevant or not. Further studies should assess these findings.

Conclusion:
Indoor air purification was associated with significant reductions in systolic and diastolic blood pressure levels, but questions arise whether these reductions are clinically relevant or not. Further studies should assess these findings.
Abstract 4144271: AI-Assisted Transseptal Puncture: Visual-Prompt Fine-Tuning of Foundation Models on Low-Dose X-RAY Images
Authors: QI Xiuyu , Wang Xingyao , Cui Chang , JU WEIZHU , Chen Minglong
Published: November 2024

Background:
Transseptal puncture (TSP) is a critical step allowing access from right atrium to left atrium in cardiac interventions. The operation relies heavily on real-time X-ray imaging and often involves subjective decision-making needing experience. Recent advancements in artificial intelligence (AI), particularly visual foundation model offer promising solutions to enhance the precision and consistency of TSP.

Research questions:
We hypothesize that a foundation model fine-tuned on real TSP images and expert annotations, can accurately predict the optimal puncture site on imaging.

Aims:
This study aims to develop and validate an AI method that automatically identifies the ideal TSP site using only the CS catheter as a reference in X-RAY image. This approach seeks to replicate the decision-making process of experienced clinicians, thereby improving the accuracy and safety of the procedure.

Methods:
A pilot study enrolled 101 patients in one center. Three experienced senior practitioners are responsible for labeling these images. To learn information from limited X-RAY images, we design a co-training framework based on Segment Anything Model (SAM) to fine-tune the decision module for TSP by combining visual prompts of the three bounding boxes (heart edge, spine, and coronary sinus electrode). The input images are captured before puncture and resized to 512*512. The candidate puncture area is set as a circle centered at actual puncture point with a radius of 10 pixels.

Results:
Images from 80 patients were used to fine-tune the decision module, while 21 for validation. The Intersection over Union (IoU) on validation set is 70.22% for the pre-defined candidate TSP circle. In validation, the success rates of the predicted TSP point (the center of the predicted area) falling within radii of 5, 10, 15 pixels cantered on the actual TSP site are 56.30%, 72.01% and 83.54%, respectively.

Conclusions:
In this study, we introduce an AI-assisted visual prompt for TSP using SAM-based fine-tuning. With the limited samples, the performance of puncture-site prediction underscores the potential of our framework as an efficient solution for TSP guidance and assistance. The future works include expanding the sample size and testing whether visual prompts can enhance TSP quality and clinical training.
Abstract 4144277: Analysis risk factors of long-term adverse outcomes and construction of nomogram based on fractional flow reserve for coronary artery disease patients with an intermediate stenosis
Authors: Li Fan Qi , Liu Qiming , Xiao Yichao
Published: November 2024

Background:
The role of fractional flow reserve (FFR) in intermediate lesions has been widely demonstrated and recommended by guidelines. However, the long-term outcomes in patient with an intermediate stenosis received FFR have not yet been investigated comprehensively.

Methods:
We retrospective included 558 patients underwent both coronary artery angiography (CAG) and FFR. All patients were randomly divided into a training set containing 390 individuals and a validation set of 168 individuals at a ratio of 7:3. Valuable predictors were screened for constructing nomogram by statistical and clinical significance. The prediction efficiency of nomogram was evaluated by multiple methods, including C-index, area under the curve (AUC), calibration curves and decision-curve analysis (DCA).

Results:
During a median follow-up of 6.2 years, 87 (15.59%) adverse events were documented. The nomogram consists of age, smoking, hypertension, diabetes mellitus (DM), hyperuricemia, and FFR≤0.8 six factors. The C-index in the training and validation sets were 0.807 and 0.832. The AUC of 3-year, 5-year, 7-year receiver operating characteristic (ROC) curves of training set were 0.697, 0.823, 0.854, and of validation set were 0.845, 0.824, 0.856. The calibration curves and DCAs illustrated the ability of the nomogram to predict long-term adverse outcomes and its net benefits in clinical practice.

Conclusions:
Age, DM, and hyperuricemia were independently associated with longterm adverse outcomes, and the constructed nomogram based on FFR may be used as a visible tool to predict long-term adverse outcomes for coronary artery disease (CAD) patients with an intermediate stenosis.
Abstract 4144284: A Novel RNA Interference Agent RN0191 Lowering Proprotein Convertase Subtilisin/Kexin Type 9, Low-density Lipoprotein Cholesterol and Other Lipid Biomarkers in Healthy Volunteers with Elevated LDL Cholesterol: A Randomized, Single-blind, Placebo-controlled, Phase 1 Trial
Authors: wang fangfang , Li Haiyan , Zeng Jie , Shi Stella , Li Hongmei
Published: November 2024

Background:
Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, leading to their degradation and decreasing serum LDL-cholesterol (LDL-C) to reduce risk of coronary heart disease. We aimed to investigate the safety, tolerability, pharmacodynamic characteristics of RN0191, a novel structure small interfering RNA that inhibits PCSK9 mRNA translation process, in healthy Chinese adults with elevated LDL-C who were not on lipid-lowering treatment.

Methods:
We did a randomized, single-blind, placebo-controlled, Phase 1 dose-ascending study in healthy Chinese volunteers with serum LDL-C≥100 mg/dL (2.6 mmol/L). Subjects were randomly assigned in a 6:2 ratio to receive single subcutaneous injection of RN0191 (dose ranging from 60mg to 600mg) or placebo. Primary endpoint was the safety and tolerability of RN0191. Secondary endpoints included RN0191's pharmacodynamic effects on PCSK9, LDL-C and other lipid biomarkers. All subjects were masked to treatment assignment. The study registered in ClinicalTrials.gov (NCT06132360) and is still on-going.

Results:
Of 32 subjects, 24 were randomly allocated to receive a single dose (60mg/200mg/400mg/600mg) of RN0191 (6 in each active arm) and 8 to placebo. The analysis spans all cohorts at Day 56 post-administration. All the adverse events are mild or moderate. There is no severe treatment-emergent AE (TEAE), death or TEAE leading to study discontinuation. The numbers of subjects affected by TEAEs in each cohort of RN0191 (3,4,2,2) are similar to that of placebo (3). The interim data indicates a profound dose-dependent lowering impact of RN0191 on several key lipid biomarkers. Substantial PCSK9 protein reduction is demonstrated in a dose-dependent manner. In high dose (400 mg and 600 mg) cohorts, mean maximal decreases of PCSK9 level of 85.84% on Day 21 and 86.14% on Day 28 are achieved respectively. Notably, LDL-C exhibits progressively greater reductions across escalating doses. The mean maximal decreases of LDL-C are achieved as 54.65% of 400mg cohort on Day 42 and 51.35% of 600mg cohort on Day 21 respectively. Additionally, a significant lipoprotein (a) reduction is observed with mean maximal lowering level of 43.95% at 400mg cohort on Day 21 and 52.95% at 600mg on Day 28 respectively.

Conclusions:
The preliminary safety and efficacy profile of RN0191 underscoring its comprehensive lipid-lowering capacity as a promising therapeutic candidate for managing dyslipidemia.
Abstract 4144299: Association of Sleep and Exercise with Chronic Disease: Insights from Long-Term Wearable Data Among All of Us Participants
Authors: Kalyanasundaram Asanish , Barber Jacob , Mi Michael , Keyes Michelle , Tahir Usman , Robbins Jeremy , Peters Nicholas , Sofer Tamar , Kramer Daniel , Gerszten Robert , Rao Prashant
Published: November 2024

Introduction:
Sleep and physical activity (PA) are essential components of ideal health. However, epidemiological data assessing PA and sleep have been limited by short measurement periods, small samples, or recall bias. We assess the relationship between objective measures of long-term PA and sleep across the human phenome.

Methods:
We included 9399 individuals in the All of Us cohort with >6 months of wearable (Fitbit) data and linked electronic health records. Fitbit data included daily total sleep duration (TSD) and moderate and vigorous physical activity (MVPA) over a median time of 1103 days. We used Cox regression to model the association of MVPA and TSD across 1711 phecodes (Cox pheWAS), adjusting for age, sex, and race. Top associations were investigated individually using restricted spline curves to quantify the change in hazard ratio (HR) of disease per minute of sleep or MVPA. Individual phenotype associations were further adjusted for smoking status, alcohol intake, education level, and BMI. We performed interaction analyses to assess whether TSD modifies the effect of MVPA on disease. We accounted for multiple hypothesis testing with Bonferroni correction.

Results:
TSD and MVPA levels were uncorrelated (r2: 0.004) and independently associated with several cardiometabolic and non-cardiometabolic diseases, including obesity (MVPA: HR 0.97, p 4e-14; TSD: HR 0.99, p 2e-16), hypertension (TSD: HR 0.99, p 4e-5), major depressive disorder (MVPA: HR 0.98, p 2e-7; TSD: HR 0.99, p 3e-3), and chronic migraine (MVPA: HR 0.97, p 3e-5) (Fig.1). The association between MVPA and chronic disease often demonstrated a linear or curvilinear dose-response curve. By contrast, the association of TSD and chronic disease was often sigmoidal, with increasing benefit of longer sleep between ~5hr20min and 6hr40min of sleep/day, but relatively constant health benefits/risks for longer/shorter sleep durations.

Conclusion:
In All of Us participants, TSD and MVPA are independently and inversely associated with chronic disease based on objective, long-term measures. These data highlight the importance of
both
sleep and MVPA in maintaining ideal health, and will help inform personalized, disease-specific sleep and PA recommendations.