bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4139977: Aggressive LDL cholesterol lowering post ACS with triple combination therapy: Insights from the multicentric LAI-REACT study
Authors: Puri Raman , Mahajan Kunal , Agarwala Rajeev , Gupta Ashu , Batra Aditya , Khan Aziz , Vijan Vinod , Sharma Jai Bharat , Himral Surender
Published: November 2024

Background:
Patients with acute coronary syndrome (ACS) face a high risk of recurrent events in the early post ACS period. Rapid reduction of low-density lipoprotein cholesterol (LDL-C) is crucial, but high-intensity statins (HIS) alone often fall short of goals.

Research Hypothesis:
Early use of triple combination therapy of HIS with non-statin drugs: ezetimibe and bempedoic acid (BA) is likely to help achieving the target goals rapidly.

Aim:
The LAI-REACT (Lipid Association of India Recommended Early and aggressive lipid lowering in ACS with triple Combination Therapy) study evaluated the LDL-C lowering efficacy of a novel triple combination REB (40 mg rosuvastatin, 10 mg ezetimibe, and 180 mg bempedoic acid daily), in patients with ACS.

Methods:
The multicentric LAI-REACT study enrolled 369 statin-naïve ACS patients across five Indian centers. All received the triple REB combination upon admission. Lipid profiles were assessed at baseline and weeks 1, 2, 4, and 6.

Results:
The mean age of the study population was 56.3 ± 11.3 years. The mean LDL-C at admission was 119.2 ± 37.1 mg/dL, which significantly decreased to 49.4 ± 19.3 mg/dL at week 1, 44.7 ± 17.4 mg/dL at week 2, 44.6 ± 16.6 mg/dL at week 4, and 46.7 ± 18.3 mg/dL at week 6. The percentage reductions in LDL-C at weeks 1, 2, 4, and 6 were 58.6%, 62.5%, 62.6%, and 60.8% respectively (repeated measures ANOVA, p<0.001). Similarly, non-HDL cholesterol levels demonstrated significant reductions of 53.1%, 54.7%, 54.6%, and 54.9% at weeks 1, 2, 4, and 6 respectively (repeated measures ANOVA, p<0.001). Mean apo-B levels decreased from 92.3 ± 23.6 mg/dL at admission to 65.2 ± 24.1 mg/dL at week 4 (29.4% reduction). Target LDL-C < 70 mg/dL was achieved in 87.3%, 92.1%, 93.2%, and 90.5% of patients at weeks 1,2,4 and 6 weeks respectively. Similarly, target LDL-C < 50 mg/dL was achieved in 55.2%, 70.6%, 69.6% and 64.6% of patients at 1,2,4 and 6 weeks respectively.

Conclusion:
The LAI-REACT study demonstrates the rapid and sustained efficacy of triple REB therapy in achieving LDL-C goals after ACS. Significant reductions in LDL-C were observed as early as the first week and were maintained up to the sixth week of follow-up. This affordable regimen provides an alternative to more expensive inhibitors of proprotein convertase subtilisin/kexin type 9, potentially improving access to effective lipid-lowering therapy in India.
Abstract 4139982: Ventricular Pre-excitation Related Cardiac Dysfunction Secondary to Accessory Pathway in the Absence of Tachyarrhythmia: A Systematic Review
Authors: Rahman Mansoor , Alayyat Ahmad , Aziz Sundal , Haseeb ul Rasool Muhammad , Ullah Waqas , Pavri Behzad
Published: November 2024

INTRODUCTION:
Asynchronous ventricular pre-excitation over an accessory pathway (AP) in the absence of tachyarrhythmia is sometimes reported to cause left ventricular dysfunction (LVD).

AIMS:
To analyze the pathophysiological mechanism, role of AP location, evaluation modalities, and management of pre-excitation-related LVD.

Methods:
PubMed and Google Scholar databases were searched for reports on pre-excitation-induced LVD regardless of patient's age, and publication date.

Results:
Out of 11,775 citations retrieved, 53 met inclusion criteria, including 41 case reports and 12 observational studies with 611 total participants, age range of 1.14-60.8 years, and M: F of 325:265 (Table). At initial presentation, acute HF was common in pediatric patients, with poor response to medical therapy; while adults were more often asymptomatic. Right septal and right free wall were the commonest APs location associated with LVD. Amiodarone and propafenone achieved improvement in HF status by causing AP block and restoring ventricular synchrony in pediatric patients deemed unfit for catheter ablation (CA). Septal dyskinesia (SD) and intra-LV dyssynchrony (ILVD) were the key pathophysiological mechanisms causing LVD, leading to regional myocardial wall thinning and hypotrophy. Two-dimensional strain echocardiography (2D-STE) was used in quantifying regional myocardial strain, noninvasive localization of APs, and assessing therapeutic response to CA. Systolic intervals ratio [(pre-ejection period (PEP)/LV ejection time (LVET)] assessed via continuous Doppler detected derangement in LVEF with high accuracy. Preexcitation-induced myocardial changes were usually reversible after CA of APs with recovery of LV function. However, irreversible myocardial tissue damage even after CA was reported, especially in adults. Resolution of ILVD and SD in the immediate post-CA period was predictive of response to CA.

Conclusions:
We report the largest aggregation of data regarding preexcitation-induced LV dysfunction. Long-term asynchronous activation of the LV via an AP, even without tachyarrhythmias, can causes adverse myocardial changes leading to cardiac dysfunction, especially in children with right-sided APs. 2D-STE and systolic intervals (PEP/LVET) are efficient tools for evaluation. Ablation of APs usually restores cardiac function largely; however, irreversible myocardial fibrosis can ensue. Based on these data, early CA of the APs associated with LV dysfunction is, therefore, recommended.
Abstract 4139988: Optimal Unipolar and Bipolar Electrode Separation for Recording Atrial Fibrillation in Patients
Authors: Rodrigo Miguel , Ruiperez-Campillo Samuel , Narayan Sanjiv
Published: November 2024

Background:
Ablation is an increasingly preferred treatment for patients with atrial fibrillation (AF), yet the optimal catheter configuration to record electrical activity (electrograms) is undefined. It is unclear what electrode spacing includes local activity or remote colliding waves. This may affect the certainty that potentials near pulmonary vein or other targets are local, or truly eliminated by ablation, for different catheter designs.

Hypothesis:
We hypothesized that unipolar and bipolar electrograms in AF are impacted differently by electrode spacing, and that even adjacent bipolar electrograms may vary and reflect direction more than local activity.

Methods:
We studied 35k electrograms in N=22 patients referred for AF ablation (67±10 y.o, 3 female, 15 non-paroxysmal), collected with both grid-type (3 mm spacing; Abbott) and basket (6-8 mm spacing; Abbott) catheters. For each patient, we precisely measured separation in electroanatomic 3D shells from (x,y,z) coordinates for all electrode pairs (adjacent, next adjacent…) within and between catheters (N=12 patients had simultaneous grid/basket; fig. A). We compared similarity of AF electrograms for 1 to 20 mm distances using the Pearson correlation coefficient (CC), for unipolar and bipolar configurations, in 500ms cycle length windows.

Results:
Unipolar electrograms in AF were more similar over distance than bipoles. For unipoles, Fig B shows that AF electrograms had CC~0.8-0.9 for electrodes <2-3 mm apart, within a grid sizes, and CC>0.8 for spacing up to ~6 mm, within basket sizes. For distance > 6 mm, CC dropped in a semi-linear fashion with exponential increase in variability (p<0.05). For bipolar electrograms (fig. C), consistency was observed only partially even for very close electrodes (CC >0.8 for <2mm spacing), then fell rapidly with exponential variability (3-10mm). Fig C shows examples where even for relatively close bipoles, EGM traces showed different activation sequences (black arrows).

Conclusions:
Mapping in AF is very sensitive to unipolar or bipolar electrode configuration. Unipolar electrograms are similar for 2-6 mm separation, while bipolar electrograms vary for spacing >2 mm which may reflect direction more than local activity. Future studies should calibrate these findings against optical recordings of wave propagation or results from prospective guided ablation.
Abstract 4139995: Scoring System-Based Approach for Identifying Patients With Positive Intracoronary Acetylcholine Provocation Tests: The Original and Modified ABCD Score
Authors: Ohnaga Yoshiyuki , Saito Yuichi , Kitahara Hideki , Kobayashi Yoshio
Published: November 2024

Background:
Although intracoronary acetylcholine (ACh) provocation testing is a guideline-recommended invasive standard for the diagnosis of vasospastic angina (VSA), ACh tests are largely underused in clinical practice globally. Recently, Rinaldi et al. developed a risk-scoring system, the ABCD score, to predict positive ACh test results. However, the ABCD score, consisting of clinical presentation, myocardial bridge, C-reactive protein, and dyslipidemia, has not been externally validated yet. We aimed to examine the diagnostic ability of the score and attempted to improve the predictivity for identifying patients with VSA.

Methods:
From May 2012 to September 2023, a total 1029 patients underwent ACh provocation test for diagnosing VSA. Patients without data on C-reactive protein and high-density lipoprotein cholesterol and those who had a history of coronary artery bypass grafting and stenting in the left anterior descending artery were excluded. The original and modified ABCD score were calculated as shown in Figure 1. The positive ACh provocation test (i.e. VSA) was defined as significant angiographic vasospasm accompanied by chest pain and/or ischemic electrocardiographic changes.

Results:
Of the 723 patients included in this study, 383 (53.0%) had positive ACh provocation tests. The receiver operating characteristics curve analysis indicated that the original ABCD score was significantly predictive of VSA, but the diagnostic ability was modest (Figure 2). Using best cut-off values on receiver operating characteristics curve analyses, we developed the modified ABCD score (Figure 1), resulting in significantly greater diagnostic accuracy (Figure 2). The modified ABCD score better stratified positive ACh test results than the original score (Figure 2).

Conclusions:
The original ABCD was predictive of VSA in this external validation study with modest diagnostic accuracy. The modified ABCD score achieved better predictivity for identifying patients with VSA.
Abstract 4140060: Impact of SGLT2 Inhibitors on Mortality Risk in Type 2 Diabetes Mellitus and Coronary Artery Disease: A Systematic Review and Meta-Analysis
Authors: Gonzales Antony , Collantes-Silva Nicole , Arambulo-Castillo Sebastian , Ortiz-Benique Zhamanda N. , Munoz-Moreno Juan Manuel , Alarcon Esteban
Published: November 2024

Introduction:
Type 2 diabetes mellitus (T2DM) is a major risk factor for coronary artery disease (CAD). SGLT2 inhibitors (SGLT2i) are effective in reducing cardiovascular mortality in T2DM patients, but their benefits for those with both CAD and T2DM are uncertain.

Objective:
The primary outcome was to evaluate the efficacy of SGLT2i compared to other hypoglycemic agents or placebo in reducing the risk of all-cause mortality in patients with T2DM and CAD. Secondary outcomes included cardiovascular death, fatal or non-fatal stroke, and fatal or non-fatal myocardial infarction. We hypothesize that SGLT2i are more effective in mortality risk reduction in patients with T2DM and concomitant CAD.

Methods:
A systematic review following PRISMA-2020 guidelines was conducted across four databases to evaluate the efficacy of SGLT2i in reducing mortality risk in diabetic patients with CAD. Quantitative analysis using Stata v18 employed a random-effects model (Restricted Maximum Likelihood) with Hazard Ratios (HR) as the measure of association.

Results:
Out of 853 studies identified, 5 publications were included in the final quantitative analysis, which included 5225 patients. The Newcastle-Ottawa Quality Assessment Form showed all included cohort studies had a low risk of bias. Those patients taking SGLT2i had a significant reduction in 38% the risk of all-cause mortality (HR 0.62 [0.47, 0.80]), this same effect was observed when compared with each subgroup vs. other hypoglycemic agents, HR 0.52 [0.29, 0.93]; vs. placebo, HR 0.64 [0.46, 0.90]. Results show very low heterogeneity. In overall cardiovascular death analysis, a significantly greater reduction was observed with SGLT2i (HR 0.61 [0.46, 0.81]), as well as when compared with placebo (HR 0.64 [0.47, 0.86]). In contrast, when compared with other hypoglycemic agents, there was a reduction, but this was not significant (HR 0.45 [0.19, 1.03]). No statistically significant decrease in the risk of fatal or non-fatal stroke and myocardial infarction was found with SGLT2i.

Conclusion:
SGLT2i demonstrates a greater significant benefit in reducing all-cause and cardiovascular mortality in patients with T2DM and CAD.
Abstract 4140065: Feasibility of Self-Expanding Transcatheter Pulmonary Valves in Patients with Pyramidal RVOT: Favorable Mid-term Outcomes
Authors: Zhu Wenhao
Published: November 2024

Background:
Transcatheter pulmonary valve replacement (TPVR) has been acknowledged as a common and beneficial treatment for significant pulmonary regurgitation (PR), but data are still lacking about the mid-term effects of self-expanding valve implantation in patients with pyramidal right ventricular outflow tract (RVOT).

Methods:
This study was a multicenter retrospective analysis involving consecutive patients who underwent intentional TPVR between May 27, 2014, and September 14, 2023. Baseline characteristics and immediate/mid-term echocardiographic variables were gathered and compared among patients with pyramidal RVOT and those with other RVOT configurations. The primary endpoint of immediate device success rate and secondary endpoint within one year post-procedure were also evaluated in both groups.

Results:
A total of 68 patients were enrolled in the study. The primary endpoint showed a marginal difference between the two groups, with a significance level of P = 0.067 (86.7% in the pyramid-type group versus 100% in other types). At 1-year follow-up, the secondary endpoint demonstrated no intergroup differences in outcome (91.7% versus 86.0%; P = 0.605). Echocardiographic improvement and mid-term clinical outcomes were comparable in both groups (all P > 0.05). However, prosthesis valves implanted in pyramidal RVOT were observed to be more prone to developing trivial regurgitation within the first month (6 out of 11, 54.5% versus 7 out of 45, 15.6%; P = 0.016).

Conclusions:
Despite slightly lower immediate device success rates, the outcomes of Venus P-Valve implantation in pyramidal RVOT were not only acceptable but favorable during mid-term echocardiographic and clinical follow-up. The utilization of self-expanding valves has significantly broadened the indications for TPVR, necessitating specific morphology assessments to better guide future procedures.
Abstract 4140068: Apical resection preserves the proliferative capacity of cardiomyocytes located throughout the left ventricle of the heart
Authors: NGUYEN THANH , Nakada Yuji , Wei Yuhua , Zhang Jianyi
Published: November 2024

Background:
When newborn pigs underwent apical resection (AR) surgery on postnatal day (P) 1, the apex fully regenerated by P28, and when pigs underwent AR on P1 (AR
P1
) followed by myocardial infarction (MI) surgery on P28 (AR
P1
MI
P28
), or MI on P28 without previous AR surgery (MI
P28
-only), a large infarct persisted in hearts from the MI
P28
-only group on P56, while AR
P1
MI
P28
hearts had little evidence of scarring at the same time point, and the improvement appeared to be driven primarily by cardiomyocyte (CM) proliferation. Thus, whereas mammalian CMs normally undergo cell-cycle arrest just a few days after birth, AR
P1
prolonged the duration of CM cell cycle activity and the cells’ proliferative capacity through at least P28.

Hypothesis:
The two surgical procedures were performed ~5 mm (AR) and ~20 mm (MI) above the heart base; thus, we hypothesize that AR
P1
preserved the cell-cycle machinery of CMs located throughout the left ventricle (LV), rather than only near the resection site.

Approach:
CM single-nucleus RNA sequencing (snRNAseq) data were collected from uninjured (CTL) pigs on P14 (CTL-P14) and from the apex zone (AZ) and remote zone (RZ) of the LV in AR
P1
pig hearts on P2, P4, P8, and P15. These data were integrated with data collected from AR
P1
hearts on P28, from the hearts of CTL pigs on P1, P2, and P28, and from the hearts of fetal pigs (Fetal) in our previous studies, and then the expanded snRNAseq dataset was evaluated with our cell-cycle-specific Autoencoder to identify clusters of cycling CMs, which were defined by the co-enrichment of each of five markers for cell-cycle activity or proliferation (AURKB, MKI67, INCENP, BIRC5, and CDCA8). CM proliferation was also evaluated in AR
P1
hearts on P15 and CTL hearts on P14 via immunohistological analysis of phosphorylated histone 3 (PH3) and symmetric Aurora B (sAUB).

Results:
Cycling CMs were significantly more common in Fetal hearts and in both the AZ and the RZ of AR
P1
hearts on P8 and P15 than in CTL hearts on P14. PH3- and sAUB-expressing CMs were also more common in the AZ and RZ of AR
P1
hearts on P15 than in CTL hearts on P14.

Conclusion:
AR
P1
preserved the cell-cycle activity and proliferative capacity of CMs throughout the LV.
Abstract 4140072: Icosapent Ethyl-Associated New Atrial Fibrillation Incidence compared to Omega-3 Fatty Acids: An Observational Cohort Study
Authors: Sarker Jyotirmoy , Patton Samantha , Kim Michael , Radwanski Przemyslaw , Munger Mark , Kim Kibum
Published: November 2024

Introduction:
Icosapent ethyl (IE), an ethyl ester derivative of eicosapentanoic acid (EPA), and omega-3 acid ethyl esters, an ethyl ester derivative of both EPA and docosahexaenoic acid (DHA), are approved as adjunct to statin therapy for reducing MACE in patients with elevated triglyceride levels. There are concerns regarding atrial fibrillation (AF) risk associated with IE. This study aims to assess the incidence of AF while receiving IE versus omega-3-acid ethyl esters (DHA/EPA), both alongside baseline statin therapy.

Methods:
In this retrospective cohort study, we used data from the Merative MarketScan Commercial Claims and Medicare Supplemental Databases (2013-2021). Adult patients on statin therapy who initiated either IE or DHA/EPA were identified using outpatient dispensing records. Patients with an AF diagnosis during the one-year baseline period were excluded. Patients were followed for up to two years to assess the incidence of AF. Censoring occurred if there was treatment discontinuation, switching between treatments, end of enrollment, or end of the study. Patients experiencing events or being censored within the first 30 days were also excluded. Propensity score matching was used to create comparable groups, with exact matching on time periods (2013-2015, 2016-2018, and 2019-2021). Using Cox proportional hazard regression model, we calculated hazards ratio of the onset of AF for IE versus DHA/EPA.

Results:
The analytic cohort consisted of 17,638 matched pairs. Patients in both groups had a median age of 56 years. Male patients accounted for a 65.7% of the IE group and 64.5% of the DHA/EPA group. Baseline cardiovascular risk factors were well matched between both groups. The 2-year cumulative incidence of AF for IE and DHA/EPA groups were 5.322% and 3.994%, respectively, resulting in a HR of 1.257 [95% CI,1.159-1.364], p=0.0032. (Figure 1)

Conclusions:
IE is associated with a higher risk of AF compared to DHA/EPA combined products, indicating the need for careful risk-benefit discussion between clinicians and patients considering IE therapy.
Abstract 4140203: Prognosis of Cardiovascular Magnetic Resonance Myocardial Characterization Among Individuals with Undifferentiated Non-ischemic Cardiomyopathy
Authors: Zhang Lu , Jha Mawra , Shenoy Ujwala , Manning Warren , Tsao Connie
Published: November 2024

Background:
Contrast cardiovascular magnetic resonance (CMR) is the gold standard non-invasive method to characterize the left ventricular (LV) myocardium, yet its role in heart failure (HF) prediction in undifferentiated non-ischemic cardiomyopathy (uNICM, without etiology) is unclear.

Aim:
To evaluate CMR myocardial tissue characteristics [late gadolinium enhancement (LGE), native T1 mapping, and extracellular volume (ECV)] in HF diagnosis and prognosis among patients with uNICM.

Methods:
From 3583 consecutive patients referred for clinical CMR at our center (2019-2023), we identified patients with uNICM, with or without HF, based upon presence of: elevated T1 or ECV, non-ischemic LGE (e.g., mid-wall, subepicardial, transmural in patchy or non-coronary distribution), global LV dysfunction, and/or conclusion of uNICM. Individuals without HF were assessed for incident HF by physician medical record review. Multivariable (MV) regression models were used to assess the association between T1, ECV, and LGE with prevalent and incident HF.

Results:
Among 782 patients with uNICM, 379 had all CMR variables of LV structure and function (59±15 y; 36% F, 48% prevalent HF). Patients with HF had less favorable LV function and structure: ejection fraction (37 vs. 50%), mass index (71 vs. 64 g/m
2
), end-diastolic volume index (121 vs 100 ml/m
2
), T1 (1287 vs 1259 ms), and ECV (34 vs 31%), all p<0.001, except LGE (51 vs 59%, p = 0.150). In MV models, elevated T1 and ECV, but not LGE, were associated with prevalent HF (
Table
). In patients without prevalent HF (n=196), 33% patients developed HF over a median follow-up of 13 (IQR: 3-23) months. Elevated ECV conferred a >2-fold risk for incident HF (HR 2.77, 95%CI:1.36-5.66, p=0.005) in MV models (
Table
,
Fig
).

Conclusion:
Elevated ECV, possibly indicating diffuse fibrosis, is associated with both prevalent and incident HF in patients with uNICM referral for CMR. Larger studies may allow study of the prognosis of these measures in other hard outcomes.
Abstract 4140204: Relationship of Oxidized Phospholipids and Lp(a) to Outcomes after Acute Coronary Syndrome: A Post Hoc Analysis of the ODYSSEY OUTCOMES Trial
Authors: Tsimikas Sotirios , Szarek Michael , Cobbaert Christa , Reijnders Esther , Jukema J , Bhatt Deepak , Bittner Vera , Diaz Rafael , Fazio Sergio , Garon Genevieve , Chong Yuan , Gong Xiaomin , Goodman Shaun , Harrington Robert , White Harvey , Zeiher Andreas , Steg Philippe , Schwartz Gregory
Published: November 2024

Background:
Oxidized phospholipids (OxPL) are preferentially carried by and contribute to the pro-inflammatory properties of lipoprotein(a) [Lp(a)]. OxPL can be quantitated on all apolipoprotein B-100 containing lipoproteins (OxPL-apoB), a dominant proportion of which are present on Lp(a) particles.

Objectives:
To assess the effect of PCSK9 inhibition by alirocumab on plasma levels of OxPL-apoB, and the relationship to Lp(a) and major adverse cardiovascular events (MACE) in patients with a recent acute coronary syndrome (ACS) on optimized statin treatment.

Methods:
OxPL-apoB (Diazyme, Inc) and Lp(a) (TinaQuant, Roche Diagnostics) were measured at baseline (1-12 months after ACS) in a subset of participants in the ODYSSEY OUTCOMES trial with samples available at baseline (prior to randomization to alirocumab or placebo, n=11,630) and log
2
-transformed. Proportional hazards models adjusted for 12 baseline covariates evaluated the association of predictor variables (OxPL-apoB and Lp(a)) with MACE (coronary heart disease death, non-fatal MI, ischemic stroke, and hospitalized unstable angina) and all-cause death, with HRs for doubling of the predictor variable.

Results:
Baseline OxPL-apoB correlated with Lp(a) (r=0.68, p<0.001). At 4-months, ALI reduced median (IQR) PBO-corrected OxPL-apoB by 15%, P<0.001. In the placebo group, when analyzed in separate models with multivariable adjustment, pre-randomization OxPL-apoB (HR (95% CI) 1.081 (1.026-1.139), p=0.003) and Lp(a) (HR (95% CI) 1.080 (1.041-1.120), p<0.001) each predicted MACE. However, when OxPL-apoB and Lp(a) were placed in the same model only Lp(a) remained significant (HR (95% CI) 1.069 (1.023, 1.118), p=0.003). In the alirocumab group, neither baseline OxPL-apoB nor Lp(a) predicted MACE in individual or joint models. Baseline high sensitivity C-reactive protein predicted all-cause death, but OxPL-apoB and Lp(a) did not.

Conclusions:
In statin-treated patients with recent ACS assigned to placebo, the increased risk of MACE due to elevated OxPL-apoB appears to be mainly driven by their presence on Lp(a). In patients assigned to alirocumab, these variables were not predictive of MACE, suggesting mitigation of OxPL-apoB and Lp(a)-mediated risk by alirocumab.
Abstract 4140212: Cardiac Electrophysiologic Response to Single-dose AUX-001, a Once-Daily Extended-Release Nicorandil in Development for Chronic-stable Angina in Adult Healthy Volunteers under Fasting and Fed Conditions
Authors: Tigoer Uwe , Chabowski Dawid , Fonseca Marlene
Published: November 2024

INTRODUCTION:
Nicorandil, a dual mechanism anti-anginal used in Europe, Asia, and Australia for >20 years acts as NO donor and K
+
ATP channel opener, providing balanced pre- and afterload vasodilation. Antianginal efficacy matches beta and calcium channel blockers, and long-acting nitrates but without tolerance build-up. Immediate release nicorandil (IR NIC) taken 2-3 times daily with 80% dose release in 45 min, requires high patient adherence. While EU labeling and trials highlight no proarrhythmogenicity lack of recent data remains along with prior reports of potential impact of IR NIC on EKG patterns. Once-daily extended-release nicorandil (ER-NIC) AUX-001 is being developed to improve compliance, symptom control, and QoL for chronic stable angina patients.

ONJECTIVE:
Examine ER NIC impact on EKG patterns before and after 2 sequential 24h single-dose exposures during fed and fasting status.

METHODS:
12-lead EKG was recorded in 16 adult healthy volunteers at baseline. Peak systemic exposure of ER NIC was predicted at 6h post dose. Consequently, postdose EKG was scheduled at 6h after AUX-001 administration, with 24h monitoring. Variables included PR, ST, QT, and TP interval and P, QRS and T wave duration. QT interval was corrected using Bazett’s and Fridericia’s formula.

Results:
12-lead EKGs were available on 16 fasting and 15 fed patients. None discontinued due to safety or tolerability. 13 EKGs at baseline on day 1, and 14 on day 8 showed non-clinically relevant abnormalities. No clinically relevant abnormalities were found at baseline or 6h postdose. Mean HR was 58±5.8 and 59±6.2 at baseline and 68±8.2 and 67±6.7 at 6h for fasting and fed. Mean QTc (Bazett) was 395±19 ms pre- and 400±18 ms 6h postdose under fasting and 395±14 and 399±16 ms under fed status. Mean PR interval was 170±22 ms pre- and 160±21 ms 6h post-dose fasting and 169±17 and 158±18 under fed status.

CONCLUSION:
Single dose AUX-001 caused near no QTc changes in healthy volunteers compared to baseline. 6h postdose PR intervals physiologically adjusted to changing HR, and stayed within normal range. Similar to IR NIC, AUX-001 had no discernable effect on EKG patterns during fasting or fed conditions. Findings highlight no relevant AUX-001 effect on electrophysiological safety providing additional safety information supporting development of ER NIC. Findings also confirm previous healthy volunteer trials with IR NIC highlighting no tendency promoting arrhythmia in normal, non-ischemic myocardium.
Abstract 4140246: AI and Quantum Sensors: Realization of a Safe and Effective Unshielded Bedside Magnetocardiogram to Detect Ischemia in the Emergency Room
Authors: Iwata Geoffrey , Aschbacher Kirstin , John Sajiny , Tam Simon , Au-Yeung Kit Yee , Contreras Johanna , Bhatt Deepak , Bander Jeffrey
Published: November 2024

Introduction:
Magnetocardiography (MCG) has potential to significantly improve cardiac disease diagnosis, but adoption in clinical practice is hindered by high cost and large footprints of traditional systems. Hence, we developed a bedside, non-contact MCG system that utilizes quantum magnetometers and AI methods to extract validated cardiac biomarkers, while rejecting ambient magnetic interference.

Goal:
To investigate the safety and efficacy of the bedside MCG device in identifying non-ST-segment elevation myocardial infarction (N-STEMI) among patients from an urban emergency department.

Methods:
The MCG system is a custom prototype with 26 optically pumped magnetometers - quantum sensors that measure cardiac magnetic fields with picoTesla sensitivity. We recruited a diverse sample of 78 adult patients (72 with analyzable data) presenting to the ED with chest pain symptoms suggestive of ACS who were not experiencing STEMI (mean age=56 years; 64% male; 11% Asian, 28% Black, 7% American Indian/Alaska Native, 44% White, 1% Native Hawaiian/Pacific Islander, 9% other/unknown; 6 technically unusable recordings, 8%). A 5-minute MCG was recorded within 2 hours of an initial 12-lead ECG. Signal processing and AI algorithms were used to remove ambient interference and recover cardiac signal. Literature-based MCG markers were inputted to a classification and regression tree (CART) model to classify patients as NSTEMI ACS rule-in or rule-out.

Results:
The CART model successfully discriminated clinically determined ACS rule-in patients (n=7) from rule-outs (n=65) with sensitivity=86% and specificity=92%. The most predictive MCG markers were the field pattern angle difference between R- and T-wave maximum, the power ratio between the R- and T-waves, and the field maximum to minimum ratio. No adverse events were reported.

Conclusions:
MCG is a promising, non-contact diagnostic tool for emergency physicians diagnosing suspected ACS cases. This pilot study shows that a bedside, quantum-sensing MCG that utilizes AI has the potential to provide safe and accurate diagnostic results, and it is feasible to integrate the device into the ED workflow.
Abstract 4140279: Myeloid/Macrophage Annexin A2 Promotes Kidney Fibrosis
Authors: Lin Ling , Richardson Elyse , Hu Kebin
Published: November 2024

Background:
Annexin A2 is a Ca
2+
- and phospholipid-binding protein widely expressed in various cells and tissues. It acts as a cell surface receptor for tissue plasminogen activator (tPA) and plasminogen, regulating the homeostasis of blood coagulation, fibrinolysis and matrix degradation. However, its role in kidney fibrosis remains largely unknown. Our previous
in vitro
work has shown that annexin A2 mediates NF-κB activation and promotes macrophage M2 to M1 phenotypic change, suggesting a critical role of macrophage annexin A2 in kidney fibrogenesis.

Methods:
We generated a novel myeloid/macrophage-specific annexin A2 knockout mouse by crossbreeding LysMCre mice and annexin A2 flox mice. Unilateral ureteral obstruction (UUO) was induced in the myeloid/macrophage-specific annexin A2 knockout mice and their wildtype counterparts, as well as C57BL/6 mice. Renal histology was evaluated. Kidney fibrosis and renal annexin A2 level were examined in these mice.

Results:
After UUO injury, annexin A2 was dramatically induced in the fibrotic kidneys from C57BL/6 mice in a time-dependent manner, and its induction correlated with the extent of fibrotic injury as indicated by fibronectin deposition. Intriguingly, double immune staining analysis found that annexin A2 was dramatically induced in the interstitial F4/80-positive macrophages. It was further found that, after obstructive injury, myeloid/macrophage-specific annexin A2 knockout mice displayed significantly reduced tubular epithelial damage and dramatically decreased deposition of matrix components such as collagen and fibronectin than that of their control littermates. Additionally, obstruction-induced epithelial transdifferentiation was significantly reduced in the myeloid/macrophage specific-annexin A2 knockout mice as indicated by increase of Ecadherin and decrease of
de novo
induction of αSMA.

Conclusion:
Thus, it is clear that myeloid/macrophage annexin A2 promotes epithelial transdifferentiation and kidney fibrosis after obstructive injury.
Abstract 4140291: Unraveling the potential receptors involved in mediating globular CTRP9's protective effects in the cardiovascular system
Authors: Wyatt Kayleigh , Tan Huilan , Wu Yalin , Shila Taslima Akter , Mahmoud Amr , liu yanwen , Ma Xinliang-Xin , Zhao Jianli , Wang Yajing
Published: November 2024

Improved reperfusion strategies have significantly reduced mortality rates after acute myocardial infarction. However, chronic heart failure cases are rising. Cardiokines and adipokines, as paralog family members, share similarities in multiple aspects and play critical roles in protecting against heart failure by blocking its progression. It has been debated and remains elusive whether the CTRP family has its own receptors or shares them with other family members during disease conditions. Our previous research has indicated that globular CTRP9 (gCTRP9) plays a vital role in protecting the cardiovascular system by promoting cell proliferation and energy production in ischemic-injured hearts. However, the signal transduction mechanisms are not yet fully understood.

To address this gap in knowledge, we aimed to identify the potential cell membrane receptor for CTRP9 by analyzing the interaction between CTRP9 and three candidate receptors, namely Cadherin-13, adiponectin receptor 2, and adiponectin receptor 1. We utilized Surface Plasmon Resonance to examine the binding specificity, kinetics, and affinity of CTRP9 at a concentration of 50 µg/ml with varying levels of Cadherin-13 and Adiponectin Receptor 1, ranging from 0.1 to 100 µg/ml.

Our results showed that gCTRP9 exhibited saturation on the carboxyl chip, indicating its ability to bind to specific mobile receptors on the surface. Notably, we observed a significant binding affinity between CTRP9 and Adiponectin Receptor 1 in a dose-dependent, suggesting a stronger interaction between Adiponectin Receptor 1 and CTRP9. In contrast, Cadherin-13 also exhibited some binding affinity with CTRP9, although the response was comparatively lower. Importantly, no binding signals were detected between CTRP9 and Adiponectin Receptor 2.

In conclusion, our study provides evidence that Adiponectin Receptor 1 is a potential cell membrane receptor for gCTRP9, playing a crucial role in transmitting signals that protect injured or diabetic cardiomyocytes. Further research is needed to fully understand the downstream signaling pathways and mechanisms by which gCTRP9 and Adiponectin Receptor 1 interact to exert their protective effects on the cardiovascular system.
Abstract 4140296: Trajectory of Diastolic Dysfunction in Patients with Takotsubo Syndrome
Authors: Liu Christopher , Ouaddi Sara , Song Christopher , lou junyang , Saltzman Adam , Salmoirago-Blotcher Elena
Published: November 2024

Introduction:
Takotsubo Syndrome (TS) is associated with impairments in systolic function, but less information is available on diastolic function. Elucidating changes in diastolic function during the months following a TS episode is important to understand the long-term prognosis of this condition.

Aim:
To evaluate changes in diastolic function of patients with TS at follow-up (FU) vs. admission.

Hypothesis:
Echocardiographic measures of diastolic dysfunction will show improvements at follow-up compared to admission.

Methods:
Prospectively enrolled participants with a confirmed diagnosis of TS received a transthoracic echocardiogram at hospital admission (TTE1) and during FU (TTE2). TTE1 was performed for clinical reasons and data was abstracted from medical records. TTE2 was performed as part of an ongoing prospective study and analyzed by a cardiologist. To assess diastolic dysfunction, the following measures were considered: left atrial volume index (LAVI), e’ septal (e’s), e’ lateral (e’l), peak tricuspid velocity (TRV max), E/A, and mean E/e’. Left ventricular ejection fraction (LVEF) was also included. Differences were analyzed using paired samples t-test. P-values <0.05 were considered significant. Sociodemographic information was collected through self-report surveys. Medical and psychiatric history were abstracted from medical records.

Results:
Patients (n=49; age=64.6 ± 9.3 years) were 98% female and 94% White. At FU (average = 2.2 months), systolic function had returned to normal (p <.001). At admission, diastolic function measures were within normal range with the exception of e’s and e’l. At FU, patients showed improvements in e’l (p = < .001) and TRV max (p= 0.039). There were no changes in LAVI, E/A, and mean E/e’.

Conclusion:
In this longitudinal sample of TS patients, minimal alterations of diastolic function were detected at admission, which improved at FU. The clinical significance of these findings need further study in larger, more diverse samples.
Abstract 4140299: A Model-Sharing Approach for Quality Improvement of Diabetes and Cardiovascular Disease
Authors: Elligers Kyle , Greenway Stacey , Lambro Patricia , Sadiku Steven , Schechter Rona , WHELAN JOHN , Pressley Bianca , Sednew Renee , Duckett Sara , Pollner Meghan , Overton Katherine , Congdon Michelle
Published: November 2024

INTRODUCTION:
Opportunities exist to improve health outcomes for patients with diabetes and cardiovascular disease (CVD), or at an increased risk for CVD. The American Heart Association (AHA) established the Target: Type 2 Diabetes (TT2D) national award program to recognize hospitals and health centers for adherence to guidelines for diabetes and CVD. To focus on gaps and strategies for team-based care, coordination of care, and guideline-implementation models for diabetes and CVD, the AHA launched the TT2D Quality Collective in 2023.

METHODS:
Three health systems and three Federally Qualified Health Centers (FQHCs) were invited to participate in the TT2D Quality Collective from January 2023 – February 2025. Participation includes targeted technical support for diabetes program management, peer-supported model sharing and integration, and ongoing quality improvement support as part of AHA’s inpatient and outpatient TT2D award programs. Peer-supported model sharing is conducted through nine quarterly meetings for each Quality Collective participant to first share a successful component of their diabetes care pathway, followed by space to solicit feedback, comments, and/or suggestions for identified challenges related to diabetes care within their respective systems. Technical and quality improvement support includes seven system-specific meetings with AHA staff to inform deeper discussions around site-level barriers and strategies related to guideline-directed care. Questionnaires are administered during the initiative - at baseline, midpoint, and end - to monitor quality improvement change over time associated with participation in the initiative.

RESULTS:
Findings are displayed in Table 1.

CONCLUSION:
Diverse health systems can utilize peer-supported model-sharing and rapid feedback to identify opportunities, solutions to known barriers, and resources to improve implementation of guideline-directed care for type 2 diabetes and CVD. Initial findings from this ongoing initiative reveal the need for deeper discussions in areas such as (1) availability, access, and barriers to evidence-based pharmacological treatments, (2) treatment decision-making algorithms, (3) full integration and utilization of pharmacists as part of team-based care, and (4) strategies for increasing patient engagement in diabetes self-management.
Abstract 4140321: Assessment performance of the AHA PREVENT equations in disaggregated Asian and Hispanic Subgroups
Authors: Yan Xiaowei , Bacong Adrian , Huang Qiwen , Husby Hannah , jose powell , Palaniappan Latha , Rodriguez Fatima
Published: November 2024

Background:
New race-free Predicting Risk of Cardiovascular disease (CVD) EVENT models (PREVENT) by AHA predict 10-year total CVD, ASCVD, and heart failure (HF), respectively. Although model discrimination and calibration was generally good among Non-Hispanic White and Black, their performance among Asian and Hispanic groups, particularly in disaggregated subgroups, remain unknown.

Objectives:
We assessed PREVENT model performance in a diverse population with more than 10-year follow-up electronic health records (EHR) data in different race/ethnic groups and in disaggregated Asian and Hispanic subgroups.

Methods:
Using retrospective primary care cohort who had no baseline CVD and with at least 10-year follow-up EHR data, we estimated Harrel’s C-statistics for each PREVENT submodel and by race/ethnicity. Predicted risk based on PREVENT models verse observed corresponding CVD event risk were compared in each race/ethnicity group and Asian/Hispanic subgroups.

Results:
Over 191,000 primary care patients were identified and met the study criteria, with 58.5% non-Hispanic white (NHW), 3.2% non-Hispanic Black (NHB), 21.4% non-Hispanic Asian (NHA) and 10% Hispanic. Across three PREVENT sub-models, model performance in discriminating corresponding CVD event was comparable with those in the original model development and validation cohort, with best performed on NHA (C-statistics>0.80) for all three models, poorest on NHB (C-statistics ranges 0.75-0.77). However, each model underestimated the risk for overall population, with most underestimated for NHB, but overestimated for NHA.

Within NHA, total CVD model performed best in Asian Indian and Vietnamese (C-statistics: 0.88) and poorest on Japanese (C-statistics =0.78), ASCVD model performed best on female Vietnamese (C-statistics=0.86) and worst on female Korean (c-statistics=0.72), while HF model performed well for Asian Indian and Korean. However, total CVD model and ASCVD overestimated most for Chinese, HF overestimated most on Vietnamese (Figure 1,2,3). Within Hispanic, the models performed best in Puerto Rican.

Conclusions:
PREVENT models had significantly improved the discrimination performance in all race/ethnicity groups and disaggregated Asian and Hispanic subgroups. However, all three models underestimate risk for all groups except NHA. The variation emphasizes the importance in recognizing heterogeneity within population, individual risk should always be considered in using risk model in clinical practice.
Abstract 4140381: Does Induction Therapy with Anti-thymocyte Globulin Decrease First-year Intimal Thickening in Patients Experiencing Ischemia-Reperfusion Injury Immediately after Heart Transplantation?
Authors: Manla Yosef , Patel Jignesh , Kittleson Michelle , Kanungo Avani , Nikolova Andriana , Kransdorf Evan , Chang David , Czer Lawrence , Stern Lily , Kobashigawa Jon
Published: November 2024

Introduction:
Post-heart Transplant (HTx) ischemia-reperfusion injury (IRI) is associated with an increased risk of rejection and cardiac allograft vasculopathy (CAV). It has been suggested that induction therapy with anti-thymocyte globulin (ATG) may protect against immediate (in the first 30 days) IRI post-HTx. Additionally, ATG has been associated with reduced first-year coronary plaque progression as assessed by intravascular ultrasound (IVUS) among HTx recipients. Whether ATG can decrease first-year intimal thickening in patients experiencing IRI has not been investigated. Therefore, we aim to examine the clinical outcomes of patients who received ATG induction therapy and experienced immediate IRI post-HTx.

Methods:
Between 2010 and 2020, we assessed 241 patients undergoing HTx and were noted to have immediate post-HTx IRI on their endomyocardial biopsy. Patients were divided into those who received ATG (n=105) induction therapy vs. non-receivers (n=136). In our program, ATG is given to sensitized patients or those with baseline serum creatinine >2.0 mg/dL to delay the initiation of tacrolimus, which may introduce bias to this study. Endpoints included 1-year freedom from any treated rejection (ATR), acute cellular rejection (ACR, grade 2R or 3R), and antibody-mediated rejection (AMR, pAMR grade ≥1, 3-year survival, and 3-year freedom from non-fatal major adverse cardiac events (NF-MACE, including myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, and stroke). IVUS was performed at 4-8 weeks (baseline) and at 1 year post-HTx. Studied IVUS parameters included first-year average change in maximum initial thickness (MIT) and change in MIT ≥0.5mm.

Results:
Among patients with immediate post-HTx IRI, patients who received ATG induction therapy (57% were sensitized pre-HTx) remained at high immunological risk at 1 year with significantly lower freedom from ATR and AMR but had similar 3-year survival as compared to those who did not receive ATG (Table 1). No between-group differences were observed in the average 1-year change in MIT or the percentage of patients with ≥0.5mm change in MIT.

Conclusion:
Induction therapy with ATG did not appear to decrease first-year intimal thickening in patients experiencing IRI immediately post-HTx. Future studies are warranted to mitigate immunological complications and reduce coronary plaque progression in high-risk HTx patients.
Abstract 4140399: The Importance of Measuring Body Composition in Determining Cardiorespiratory Fitness Across the Adult Age Range
Authors: Gajjar Priya , Ravichandran Sandhiya , Sahni Shivani , Lewis Gregory , Kiel Douglas , Shah Ravi , Nayor Matthew
Published: November 2024

Background:
Maintaining cardiorespiratory fitness (CRF) is essential for healthy aging and is linked to lower risk of age-related cardiovascular diseases and frailty. However, the relations of body composition metrics and CRF levels across the adult age range are poorly understood.

Hypothesis:
Healthy body composition, characterized by higher lean mass and lower visceral and total adiposity, is associated with greater oxygen (O
2
) uptake during exercise across age and sex.

Aims:
To investigate relations of components of body composition with O
2
uptake measures during exercise and to evaluate how age and sex affect the associations.

Methods:
Framingham Heart Study participants (n=2742) underwent dual-energy X-ray absorptiometry (DXA) for body composition assessment and maximal cardiopulmonary exercise testing on a cycle ergometer at the same exam cycle. Sex-stratified linear models between DXA and O
2
uptake measures were adjusted for age, height, HDL/total cholesterol, smoking, systolic blood pressure, hypertension treatment, diabetes, and physical activity index.

Results:
The study sample had a mean age of 54±9 years, was 54% women, 9% non-white, and had a peak O
2
uptake [VO
2
] 95±20% of predicted. Higher lean mass was associated with higher peak VO
2
in ml/min in both men and women (β for standard deviation (SD) difference in log-transformed peak VO
2
for a 1-SD higher value of lean mass was 0.49 in men and 0.57 in women, P<0.0001 for both). Conversely, measures of total and visceral fat mass were associated with higher peak VO
2
in women (β= 0.14-0.15, P<0.0001) but not in men (P>0.05). The variance explained (adjusted R
2
) in peak VO
2
was higher for lean mass than other DXA measures: lean mass, age, and height explained 45-47% of the variance in peak VO
2
in men and women, while age, height, and other DXA measures explained ≤37%. Furthermore, individuals with higher observed lean mass than predicted based on age, sex, and BMI had higher observed peak VO
2
, consistent with the finding that higher lean mass is associated with higher peak VO
2
across age and sex (Figure).

Conclusion:
Maintaining lean mass across the adult age range is linked with higher peak VO
2
, which may have important implications for promoting healthy aging.