bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15154: Therapeutic Effect of Optimal Medication on Biochemical Plaque Composition in Patients With Coronary Artery Disease as Serially Assessed by Intravascular Multi-Targeted Fluorescence Lifetime Imaging Fully Integrated With OCT
Authors: Kang Dong Oh , Nam Hyeong Soo , Kim Sunwon , Han Jeongmoo , Kim Jin Hyuk , Kim Ryeong Hyun , Kim Hyun Jung , Park Ye Hee , Kim Hyokee , Song Joon Woo , Park Eun Jin , Yoo Hongki , Kim Jin Won
Published: December 2023

Introduction:
Fluorescence lifetime imaging (FLIm) is an emerging technique that can visualize detailed molecular properties of atherosclerosis. We conducted an in vivo serial molecular characterization of human coronary plaques using a fully-integrated, dual-modal, intravascular optical coherence tomography-FLIm (OCT-FLIm) system to explore the natural history of biochemical plaque composition.

Methods:
We prospectively enrolled patients with significant coronary artery disease those who underwent 6-month serial OCT-FLIm assessment for non-culprit/non-target lesions. A non-culprit/non-target lesion was defined as medically-treated angiographic mild-to-moderate stenosis diagnosed at index procedure. Biochemical plaque compositions were categorized by FLIm-derived parameters using a dedicated machine learning classifier. Each lesion was quantitatively assessed for the pre-specified plaque compositions and compared with the serial images.

Results:
Total 53 non-culprit/non-target lesions from 30 patients were enrolled. Angiography- and OCT-defined lesion severity showed no significant difference over the follow-up (p>0.05). Intriguingly, while the macrophage signal intensity decreased after 6 months (p=0.034), FLIm-based quantitative assessment revealed a worsened plaque compositional response by increased loose fibrous tissue (p=0.004) and decreased normal/fibrous tissue burden (p<0.001). These temporal changes in individual plaque components correlated well with the achieved LDL-cholesterol level at 6-month (p<0.05), whereas no correlation was found with hs-CRP (p>0.05).

Conclusion:
From this comprehensive serial assessment of human coronary atheroma by intravascular OCT-FLIm, optimal medical therapy alone was insufficient to effectively stabilize plaque composition, and additional therapeutic strategy should be explored to alter the natural course of atherosclerosis from a molecular perspective.
Abstract 15185: Plasma miR-132 Serves as a Blood Biomarker for Monitoring Treatment Efficacy of miR-132 Targeting Drugs Using a Novel CE-Marked Kit System
Authors: Viereck Janika , Rump Steffen , Rizk Sandra , Hahm Jana , Thum Thomas
Published: December 2023

Introduction:
MicroRNAs are critical regulators of cardiovascular pathophysiology and detectable in most body fluids, proposing them as circulating biomarkers. The aim of this study was to investigate if plasma miR-132 can be used as a biomarker for monitoring treatment efficacy of miR-132 targeting drugs and to develop a CE-marked kit for relative quantification of plasma miR-132.

Methods and Results:
Correlation analysis of a porcine model of post myocardial infarction (MI) induced HF revealed a dose-dependent, highly significant linear correlation between plasma and cardiac miR-132 after treatment with CDR132L. Furthermore, significant correlations between reduced plasma miR-132 and functional improvement based on LVEF change as well as reduced plasma NT-proBNP were identified. Based on this data, we developed a qRT-PCR assay for detection of miR-132. RNA was extracted from cel-miR-39 spiked plasma samples and was transcribed into cDNA with specific primers for both miRs. The miRs were amplified in two singleplex qRT-PCRs based on hydrolysis probes. Delta Cq values were calculated between Cq values of miR-132 and the miR-39 spike-in control. No cross-reaction between both assays and no amplification on human DNA or RNA were observed confirming analytical specificity. Analytical sensitivity was verified by analysis of dilution series of cDNA templates. The clinical evaluation was carried out on a subset of 119 samples from the Phase 1b clinical trial, a safety and tolerability study for CDR132L including patients with chronic ischemic HF (NCT04045405), that also assessed target engagement. CDR132L administration was associated with a dose-dependent, statistically significant reduction in plasma miR-132 at study endpoint (day 112) whereas, the highest dosing groups showed sustained low miR levels. These results were in line with miR-132 levels assessed with commercially available research use only reagents.

Conclusion:
Plasma miR-132 was validated as a suitable target engagement and therapy monitoring biomarker and the newly developed CE-marked kit “CardiorHealth miR-132 Plasma PCR Kit (IVD)“ fulfilled its intended use to quantify plasma miR-132 and can be used for monitoring treatment with drugs targeting miR-132.
Abstract 15203: Periprocedural Oral Anticoagulation for Ventricular Tachycardia Ablation and Postprocedural Stroke - Analysis of a Japanese Nationwide Inpatient Database
Authors: Makimoto Hisaki , Yamana Hayato , Isogai Toshiaki , Matsui Hiroki , Yasunaga Hideo , Kohro Takahide
Published: December 2023

Introduction:
The effectiveness and the safety of periprocedural anticoagulation for ventricular tachycardia (VT) ablation remain to be clarified.

Hypothesis:
Periprocedural anticoagulation reduces the incidence of ischemic stroke after VT ablation without increasing intracranial hemorrhage.

Methods:
Using the Japanese Diagnosis Procedure Combination database, we identified patients aged ≥18 years who underwent VT ablation from July 2010 to March 2021. The endpoints were ischemic stroke and intracranial hemorrhage which occurred during the hospitalization of the index VT ablation or led to re-admissions within three months. We performed weighted analyses using inverse probability of treatment based on propensity-score to adjust for confounding factors. We also conducted analyses stratified by antiplatelet use.

Results:
We identified 18,894 patients from 750 hospitals who underwent VT ablation (12,918 males [68%], 60.5 ± 15.7 years). Postprocedural ischemic stroke and intracranial hemorrhage were documented in 84 (0.44%) and 15 (0.08%) cases, respectively. Anticoagulants and antiplatelets were administered in 4352 (23.0%) and 5319 (28.2%) patients, respectively. Propensity score-weighted analysis demonstrated no significant association between anticoagulant use and postprocedural ischemic stroke (odds ratio, 0.91; 95% confidence interval [CI], 0.51-1.63; P=0.76). Anticoagulation was also not associated with intracranial hemorrhage (odds ratio, 2.15; 95% CI, 0.65-7.15; P=0.21). In the stratified analysis, anticoagulation was associated with an increased risk of intracranial hemorrhage in patients with antiplatelets (odds ratio, 6.30; 95% CI, 1.26-31.5; P=0.025) but not in those without.

Conclusions:
Our analysis of Japanese patients who underwent VT ablation suggests that periprocedural administration of anticoagulants may not result in a reduction of ischemic strokes and that adding anticoagulants to antiplatelet therapy may increase the risk of intracranial hemorrhage. Further studies are warranted to investigate the clinical efficacy of periprocedural anticoagulation strategy after VT ablation.
Abstract 15205: miR-132 Inhibition Improves Myocardial Strain in a Large Animal Model of Chronic Adverse Remodeling
Authors: Batkai Sandor , Genschel Celina , Viereck Janika , Rump Steffen , Traxler Denise , Gyongyosi Mariann , Thum Thomas
Published: December 2023

Background:
MicroRNAs (miRNAs) are transcriptional regulators and essential drivers of heart failure (HF). The miR-132 is necessary and sufficient to progress adverse cardiac remodeling. The strong effects are exhibited by, amongst others, cardiomyocyte hypertrophy and calcium signaling impairment. Treatments directly targeting the roots of the disease are scarce, but miR-132 inhibition by CDR132L, a rationally designed synthetic oligonucleotide, significantly improves cardiac dysfunction in HF early after myocardial infarction (MI).

Rational:
The aim of the current study was to gain further data on myocardial function and efficacy of CDR132L by analyzing left ventricular (LV) and atrial (LA) wall motion by serial cardiac magnetic resonance (cMRI) strain imaging in a clinically relevant large animal (pig) model of chronic HF.

Methods and Results:
Mangalica pigs (n=15) were randomized 1-month post-MI, initiated by left anterior descending artery occlusion followed by reperfusion as a chronic model of post-MI HF. Animals received CDR132L over 5 months by monthly intravenous treatments with 5 mg/kg. LV and LA strain parameters were deteriorated after MI over time but significantly ameliorated by CDR132L treatment, compared to placebo. Strain parameters showed significant correlations with pharmacodynamic measures such as left-ventricular ejection fraction, NT-proBNP and cardiac interstitial fibrosis in remodeling hearts 6 months post-MI.

Conclusions:
LV and LA motion and contractility were improved by repeated dosing of CDR132L with monthly frequency in a large animal model of chronic post-MI HF. The results highlight the translational value and usability of MRI-based cardiac strain imaging in HF drug development and support further clinical development of CDR132L.
Abstract 15257: The “Free Choice” Diet-Induced Obese Nonalcoholic Steatohepatitis Hamster, a Clinically Relevant Model for Evaluating Drugs Targeting Heart Failure With Preserved Ejection Fraction
Authors: Assaly Rana , Briand Francois , Brousseau Emmanuel , Maupoint Julie , Dubroca Caroline , SULPICE Thierry
Published: December 2023

Intro:
Heart failure with preserved ejection fraction (HFpEF) is frequently associated with multiple comorbidities including nonalcoholic steatohepatitis (NASH) and obesity. Drug development for HFpEF is partly hampered by the limitations of preclinical models, such as diet-induced obese mouse and rat.

Hypothesis:
To overcome these limitations, we recently established a nutritional hamster model developing obesity, with human features for dyslipidemia NASH, and HFpEF. To confirm the relevance of our model, we tested whether the clinical benchmarks empagliflozin (EMPA, a SGLT2 inhibitor), vardenafil (VAR, a PDE5 inhibitor) and semaglutide (SEMA, a GLP-1r agonist) would improve HFpEF.

Methods:
To induce obesity, NASH and HFpEF, hamsters were fed with a free choice diet, which presents hamsters with a choice between control chow or high fat/cholesterol diet, and normal or 10% fructose water for 20 weeks. Obese hamsters were then randomized based on echocardiography parameters, i.e., E/A ratio and ejection fraction (EF) and were treated QD for 5 weeks with vehicle, EMPA (30mg/kg), VAR (10mg/kg) or SEMA (0.06mg/kg). Chow fed hamsters were used as control.

Results:
Compared with control, echocardiography in obese hamsters showed cardiac remodeling, preserved systolic function and normal EF. Free choice fed hamsters had impaired diastolic function with higher E/A (2.0±0.1 vs 1.41±0.03 in control, p<0.001), while the inverted E’/A’ (0.8± 0.1 vs 1.3±0.04, p<0.001), a sign of relaxation default, suggested restrictive filling pattern. Increased E/E’ suggested higher filling pressure (18-20 vs 12-14 in control, p<0.01). Plasma NT-proBNP levels were also increased (p<0.05 vs. control). Compared with vehicle, all drug treatments alleviated diastolic dysfunction: E/A returned to control values (E/A=1.4-1.5) with VAR (p<0.001 vs. vehicle), EMPA (p<0.01) and SEMA (p<0.05). As well, E’/A’ was normalized (p<0.01 for all), and E/E’ was also reduced (p<0.05 for all). EMPA and VAR reduced NT-proBNP levels (p<0.05 vs. vehicle).

Conclusion:
Our data indicate that, VAR, EMPA and SEMA improved diastolic function in the obese NASH hamster. This novel model provides a unique alternative to mice and rats limitations for evaluating drugs targeting HFpEF.
Abstract 15258: Associations Between HV Interval and Incident Pacemaker Implant in Over 3,000 Patients
Authors: Pipilas Daniel , Sommers Thomas , Ellinor Patrick T , Khurshid Shaan
Published: December 2023

Introduction:
The His Bundle-Ventricular (HV) interval is a measure of the conduction time between the bundle of His and the ventricular myocardium and has been shown to predict atrioventricular block (AV) in patients with conduction disease. Routine HV interval measurement during electrophysiology (EP) studies affords an opportunity to assess the utility of the HV interval as a marker for future conduction disease in a broader sample.

Methods:
We analyzed consecutive EP studies from over 600,000 primary care and cardiology patients in the Mass General Brigham network. We assessed associations between HV interval and incident pacemaker (PPM) implantation in Cox proportional hazard models adjusted for age, sex, hypertension, hyperlipidemia, diabetes mellitus, coronary artery disease, heart failure, atrial fibrillation, and stroke. Person-time began 30 days after index EP study to exclude PPM implant triggered by study findings. Cumulative risk was plotted using Kaplan-Meier curves and the functional form of the relationship between HV and PPM was fit using multivariable-adjusted splines.

Results:
Of 22,019 individuals with at least one EP report, we identified 3,283 patients (age 61.1±13.6, 63% male, 91.6% White) with an HV interval measurement. In multivariable-adjusted models, a longer HV interval was associated with increased risk of PPM implant (hazard ratio [HR] 1.24 per 10ms increase, 95% CI 1.08-1.43). When assessed at binary cutoffs, there were progressively larger increases in risk of incident PPM implantation (HV ≥55: HR 1.94 (1.28-2.93); HV ≥70: HR 2.18 (1.04-4.56); HV ≥100: HR 7.75 (2.18-27.5)). PPM implant risk increased linearly until 90ms, above which risk increased sharply (Figure).

Conclusions:
Among patients undergoing EP study, a prolonged HV interval was a strong risk marker for incident PPM implantation. Patients found to have a prolonged HV interval during EP study merit close observation for the development of overt conduction disease.
Abstract 15274: STEMI as Initial Manifestation of Essential Thrombocythemia
Authors: Sanchez Christy , Donatelle Marissa A , Rogers Everett , Vedantam Karthik , Escolar Esteban
Published: December 2023

Background:
Essential thrombocythemia (ET) is a myeloproliferative neoplasm of myeloid cell expansion, mainly excessive platelet production, associated with thrombotic complications. Myocardial infarction (MI) in the setting of ET can result from thrombosis in the absence of coronary atherosclerosis. Here we present a case of ST elevation MI in the setting of previously undiagnosed ET.

Case Report:
A 59-year-old male with hypertension presented to the ED with left upper extremity weakness which started upon waking. On exam, he was in acute distress and diaphoretic. EKG revealed sinus rhythm with ST elevation in II, III, aVF, V5, and V6 suggesting inferolateral STEMI (Figure 1A). Labs were notable for Hgb 8.5g/dL, white blood cell count 33k/μL, and platelets 1.9million/μL.

Decision Making:
He was loaded with aspirin and clopidogrel (dual antiplatelet therapy-DAPT) and taken for coronary angiogram which revealed 80-90% thrombotic occlusion of the left circumflex artery (Figure 1b). Thrombectomy was performed and a drug-eluting stent was placed. A bone marrow biopsy showed JAK2 positive ET with myelofibrosis. He was immediately started on hydroxyurea. Platelets remained elevated, thus pegylated IFN alpha-2a was started which normalized platelet count. He remained on DAPT through discharge with no recurrent ischemic events or in-stent thrombosis during the 45-day hospitalization post stent placement.

Conclusion:
Patients with ET are at high risk for arterial thrombosis regardless of the presence of traditional atherosclerotic risk factors. High-risk patients, which includes those age over 60 with JAK2 mutation or history of arterial thrombosis, should be treated prophylactically with aspirin and hydroxyurea for cytoreduction. MI may be the first clinical manifestation of ET, even in patients without atherosclerotic risk factors. Initial management in patients with ET presenting with STEMI includes PCI with DAPT and early cytoreductive therapy.
Abstract 15278: Cardiac Assessments and Manifestations Among Individuals With Long-Chain Fatty Acid Oxidation Disorders: A Retrospective Claims Database Analysis
Authors: Mesa Julian , Yang Erru , Simmons Kate , Marsden Deborah , Chatfield Kathryn C
Published: December 2023

Introduction:
Long-chain fatty acid oxidation disorders (LC-FAOD) are inherited autosomal recessive defects resulting in enzyme deficiencies in the carnitine cycle or the mitochondrial β-oxidation pathway leading to deficiencies in mitochondrial energy metabolism. Cardiac manifestations, specifically cardiomyopathy and arrhythmias, are common and are leading causes of mortality in individuals with LC-FAOD.

Goal:
The goal of this study was to better understand cardiac manifestations and long-term outcomes in this group of disorders.

Methods:
The analysis was done using IQVIA PharMetrics® claims data. Individuals with confirmed LC-FAOD were identified and a non-LC-FAOD comparators group was created using 1:20 exact matching on age, gender, payer type, and enrollment start year. Cardiac-related complications were examined using ICD-10 diagnosis codes at any billing position during the study period. Cardiac diagnoses and assessments were evaluated using Current Procedural Terminology (CPT®) codes in a non-inpatient setting.

Results:
A total of 337 pediatric (peds) and 86 adult individuals with LC-FAOD were included in the study. Cardiomyopathy (peds: 8.0%, adults: 10.5%) and arrhythmias (peds: 8.9%, adults: 14.0%) were common among individuals with LC-FAOD and were significantly higher than comparators. LC-FAOD adults had significantly more cardiac conditions compared with pediatric patients and comparators. The other most common cardiac conditions among adults with LC-FAOD were chronic ischemic heart disease (18.6%), non-rheumatic mitral or tricuspid valve disorders (11.6% and 12.8%, respectively), heart failure (10.5%), atrioventricular and left bundle-branch block (7.0%), and cardiomegaly (5.1%). Individuals with LC-FAOD had significantly more cardiac related procedures than comparators. EKGs (peds: 35.9%; adults: 77.9%) and echocardiograms (peds: 44.8%; adults: 53.5%) were common among individuals with LC-FAOD.

Conclusions:
This analysis shows the importance of assessing the cardiac status of individuals with LC-FAOD. More analyses and natural history studies are needed to inform healthcare providers of cardiac risks associated with LC-FAOD and reduce mortality in these individuals.
Abstract 15344: LVAD Recipients and Caregivers Understanding of Associated Complications
Authors: Malik Aroosa , Mignery Matthew , Shore Supriya
Published: December 2023

Introduction:
Shared decision-making centers around accurate patient understanding of risk-benefits associated with a therapy. This study evaluates (i) patient and caregiver estimated risks for LVAD complications and (ii) describes how patients and caregivers rationalize estimated risks.

Methods:
We conducted a qualitative study using semi-structured interviews with 18 LVAD recipients and 9 caregivers between 1/13/2023 - 6/4/2023. Interviews were transcribed and coded, with themes identified using rapid qualitative analysis.

Results:
Included patients had a median age (range) of 60.5 (28-83) years, 12 (67%) were men, 12 (67%) were White and 10 (56%) received their LVAD as destination therapy (DT). Participating caregivers included 8 (89%) women supporting 5 (56%) DT LVAD recipients. Using the Penn Columbia Risk Score, 22% of the participants were high risk, 33% moderate risk, and 44% were low risk for mortality. When asked about patient physician communication participants ranked their interactions highly. Of all LVAD risks, both patients and caregivers demonstrated good understanding of risks of stroke and heart failure hospitalization after LVAD (89% and 72% respectively). However, both patients and caregivers described poor understanding of risks of GI bleeding and LVAD associated infections (63% patients and 25% caregivers for GI bleeding and 55% patients and 37% caregivers for infection). We identified three themes explaining how patients and caregivers rationalized under-estimation of LVAD risks (i) lack of awareness (ii) survivor bias (iii) minimization. Exemplary quotes highlighting these themes are provided in the Table below.

Conclusion:
Our qualitative study highlights the poor understanding patients have with regards to LVAD complications. This highlights the need to improve LVAD recipient and caregiver education on associated risks.
Abstract 15369: Once-Weekly Insulin Icodec versus Once-Daily Long-Acting Insulin for Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Abuelazm Mohamed T , Elzeftawy Mohamed A , Gowaily Ibrahim , badr amr , Amin Ahmed Mazen , A. Ibrahim Ahmed , Saad Elsaeidy Ahmed , Ali Shafaqat , Abdelazeem Basel
Published: December 2023

Introduction:
Insulin Icodec is a novel basal insulin analog with once-weekly subcutaneous administration. Compared to once-daily long-acting insulin (insulin glargine and degludec), insulin icodec was associated with improved glycemic control. We aim to estimate the efficacy and safety of Insulin Icodec versus long-acting insulin in type II diabetic patients.

Methods:
We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching: PubMed, Web of Science, SCOPUS, and Cochrane through May 29th, 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). Our primary outcome was glycated hemoglobin (HbA1C) change.

Results:
We included five RCTs with a total of 1,611 patients. Insulin icodec was associated with significantly decreased HbA1C (MD: -0.16 with 95% CI [-0.32, -0.01], P = 0.04) and increased percentage of time with glucose in range (TIR) (MD: 4.24 with 95% CI [1.51, 6.98], P = 0.002). However, insulin icodec was associated with increased body weight (MD: 0.63 with 95% CI [0.59, 0.67], P = 0.00001). Furthermore, there was no difference regarding hypoglycemic events incidence (RR: 1.13 with 95% CI [0.96, 1.34], P = 0.14), any serious adverse events (AEs) (RR: 1.04 with 95% CI [0.71, 1.53], P = 0.84), or AEs leading to withdrawal (RR: 1.36 with 95% CI [0.55, 3.37], P = 0.5). However, insulin icodec was associated with increased any AEs incidence (RR: 1.10 with 95% CI [1.00, 1.20], P = 0.04).

Conclusions:
Insulin icodec was associated with decreased HbA1C, increased TIR, similar hypoglycemic, and serious AEs. However, it was also associated with increased body weight and the incidence of any AEs. Further large-scale phase III real-world RCTs are required to confirm insulin icodec efficacy and safety.
Abstract 15370: Excellent Short-Term Outcomes Achieved With Minimally Invasive Right Infra-Axillary Incision and Transaortic Modified Morrow Procedure
Authors: Wang Shuwei , Wang Zhenzhen , Zhou Bing , Liu Zhifang , Luo Chentao , Wu Changhao , Han Erlei , Mei Fuyang , Lu Xiaofeng , Cui Yong
Published: December 2023

Introduction:
The Morrow procedure serves as the gold standard surgical intervention for hypertrophic obstructive cardiomyopathy. However, the conventional approach has its limitations. Minimally invasive approaches have been proposed, but exposure, mitral valve disruption, and cosmetic outcomes remain challenging. This study presents a single-port mini-incision thoracotomy through the right infra-axillary region with no surgical scar on the anterior chest wall. The procedure has achieved excellent short-term surgical outcomes.

Methods:
A comprehensive retrospective analysis was conducted, examining clinical data from 110 patients who underwent video-assisted thoracoscopic transaortic modified Morrow procedure between August 2021 and March 2023. The patient cohort comprised 62 males and 48 females, ranging in age from 15 to 71 years. Echocardiography was employed to confirm moderate mitral regurgitation in 50 patients and severe mitral regurgitation in 24 patients. Preoperatively, 102 patients exhibited systolic anterior motion (SAM). All 110 patients underwent the transaortic modified Morrow procedure, utilizing a 4-cm incision in the right infra-axillary region, with femorofemoral cardiopulmonary bypass.

Results:
There was no conversion to full sternotomy. Postoperative gradients across the left ventricular outflow tract were (7.7±4.3) mmHg. Impressively, extubation was successfully performed on the operating table for 102 patients, who experienced a median postoperative hospital stay of (9.2±3.0) days. Drainage volume in the first 24 hours was (160.4±56.0) ml. Postoperative septal thickness was (11.0±1.8) mm, and no iatrogenic ventricular septal perforation or residual SAM was observed. Follow-up at 3~22 months showed no major complications.

Conclusions:
The single-port mini-incision thoracotomy through the right infra-axillary region is a safe and effective approach for the Morrow procedure, with excellent short-term surgical outcomes and no visible surgical scar. The procedure offers several advantages, including minimal invasiveness, reduced trauma, faster recovery, and improved cosmetic outcomes. The technique is feasible and reproducible and may be a promising alternative to traditional approaches.
Abstract 15373: Guiding Modalities for Non-Culprit Artery Revascularization in Acute Myocardial Infarction With Multivessel Disease: A Pooled Analysis of FLOWER-MI and FRAME-AMI
Authors: Suebsaicharoen Thanakit , Dejprasert Wiphut , Numthavaj Pawin , Tansawet Amarit , Sasiprapha Thinnakrit , Thakkinstian Ammarin
Published: December 2023

Background:
Currently, it is not yet clear whether angiography or fractional flow reserve (FFR) is better in guiding percutaneous coronary intervention (PCI) for non-culprit artery revascularization in patients with acute myocardial infarction (AMI) and multivessel disease (MVD) after primary PCI. Therefore, a pooled analysis is conducted to summarize the findings from two only available trials, i.e., FRAME-AMI and FLOWER-MI.

Aim:
To compare major cardiac adverse event (MACE) between angiography-guided and FFR-guided non-culprit artery revascularization in AMI and MVD

Method:
MACE defined as a primary endpoint of all-cause death, non-fatal myocardial infarction, or unplanned revascularization was the primary outcome while all-cause death was the secondary outcome. Pooled cumulative probability of developing the primary endpoint curves were constructed from extracted Kaplan-Meier curves using Weibull distribution, and a meta-analysis was performed to pool extracted hazard ratio (HR) and 95% confidence intervals (CI). Furthermore, a subgroup analysis of STEMI and NSTEMI groups was performed.

Result:
Cumulative probability curve is displayed in Figure 1A. A pooled analysis showed no difference between two guiding modalities both in MACE and all-cause death risk reduction. FFR-guided PCI reduced MACE risk by 24% (HR 0.76, 95% CI 0.25-2.27) and risk of all-cause death by 47% (HR 0.53, 95% CI 0.18-1.54) compared to angiography-guided PCI but not statistically significant as shown in Figure 1B. Regarding subgroup analysis concerning MACE, FFR-guided PCI was not superior to angiography-guided PCI in STEMI (HR 1.06, 95% CI 0.60-1.90) despite significantly superior to angiography-guided PCI in FRAME-AMI NSTEMI group.

Conclusion:
FFR-guided PCI is not superior to angiography-guided PCI in non-culprit artery revascularization in AMI and MVD concerning risk reduction of MACE and all-cause death, but might show superiority in the NSTEMI subgroup.
Abstract 15374: An Energy-Harvesting Leadless Pacemaker: Proof of Principle
Authors: Gilstrap Abby , Tang Kevin , Biswas-Diener Jedi , Malakooti Mohammad H , Nazer Babak
Published: December 2023

Introduction:
Leadless pacemakers (LPM) offer several benefits over transvenous pacemakers, including lower risks of infection and vascular complications. However, their limited battery life and long-term retrieval challenges restrict their use in younger patients.

Aims:
We aim to extend the battery life of LPM by harvesting energy from right ventricular (RV) pressure fluctuations through a housing made of biocompatible piezoelectric materials, which can transduce pressure into voltage and thus recharge the battery.

Methods:
Cylindrical prototypes (n = 3) of LPM housing were fabricated using polyvinylidene fluoride (PVDF) with a thickness of 100 μm and a polyetherimide insulator wrapped around an aluminum rod, representing the LPM (1A). Our prototypes were sealed with epoxy (1B) and their dimensions (radius 9.5 mm, length 26 mm) were comparable to that of the Micra LPM (Medtronic). Prototypes were placed in a pulsatile cardiac pressure simulator (1C) and subjected to RV systolic/diastolic pressures at 1 Hz. A pressure transducer and an oscilloscope simultaneously recorded the simulator’s pressure and prototype’s transduced voltage respectively (1D). Impedance matching was performed, and an optimal resistance of 39 MΩ (1E) was identified for energy harvesting.

Results:
At oscillating “RV” pressures of 40 and 0 mmHg, our prototype generated 4 V (1D), corresponding to 52.5 nW of harvested power on an impedance-matched circuit. Under an assumed pacing output of 1.0 V at 0.24 ms and a pacing impedance of 500 Ω, each pacing stimulus requires 480 nW. Thus, our prototype can harvest 10.9% of the energy required to power an LPM.

Conclusion:
A first-generation PVDF-based energy-harvesting LPM housing can harvest approximately 10% of the power needed for pacing from RV systolic/diastolic pressures, marginally prolonging battery life. Future work will focus on increasing energy harvesting through material selection, device structure, and circuit design.
Abstract 15400: Association of Cardiovascular Health With Early Carotid Artery Changes in Young Adults From Disadvantaged Social Backgrounds: The Future of Families and Child Wellbeing Study (FFCWS)
Authors: Lloyd-Jones Donald M , Notterman Daniel , Goldman Noreen , Allen Norrina B , Marma Amanda M , Ning Hongyan , Tracy Russell , Hou Lifang , Zheng Yinan , Joyce Brian , Van Horn Linda , Korcarz Claudia E , Hansen Kristin , Stein James H
Published: December 2023

Introduction:
Associations of cardiovascular health (CVH), as measured by the AHA’s Life’s Essential 8 (LE8) score, with early markers of arterial injury have not been described in young adults.

Methods:
The FFCWS enrolled 4898 mother-baby dyads at delivery in 20 US cities in 1998-2000, oversampling mothers who were unmarried, including a disproportionate number of minority and low-income families. In 2021-23, offspring were invited to attend an in-person exam to measure CVH and perform carotid artery ultrasound. Individual CVH metric and overall LE8 scores (except sleep) were calculated for each participant (ppt). Carotid imaging was performed by 2 trained sonographers and images were analyzed by a core lab. We examined cross-sectional associations of LE8 scores with measures of carotid intima-media thickness (IMT), gray scale (a measure of early arterial injury), and distensibility, using linear regression.

Results:
Among 1211 offspring ppts, mean age was 22y, >50% self-identified as female, and >75% as Black or Hispanic. Black and Hispanic ppts had lower, and ppts from Other racial/ethnic groups had higher, overall LE8 scores compared with White ppts (all P≤0.01; Table 1A). In unadjusted analyses, Black ppts had thicker carotid IMT and lower Young’s elastic modulus measures. Prevalence of diagnostic plaque was low. In analyses adjusted for age, sex, and race/ethnicity (Table 1B), LE8 scores were significantly associated with lower carotid IMT, higher gray scale median, and lower Young’s elastic modulus. For example, for each 10 point higher (better) LE8 score, mean-maximal carotid IMT was lower by 0.008 mm.

Conclusions:
Among young adults largely from disadvantaged social backgrounds, the LE8 score was associated with early measures of carotid arterial injury. LE8 may be an important surrogate measure for monitoring long-term CVH and may help identify young adults with emerging subclinical disease and higher long-term cardiovascular risk.
Abstract 15405: Changes in Cardiometabolic Risk Factors Following SARS-CoV-2 Infection
Authors: Varghese Jithin Sam , Guo Yi , Ali Mohammed K , Donahoo William Troy , Chakkalakal Rosette J
Published: December 2023

Introduction:
Post-acute sequelae of SARS-CoV-2 infection consist of pulmonary and extrapulmonary conditions, including a higher incidence of type 2 diabetes, but it remains unknown whether other cardiometabolic pathways are impacted by infection.

Research Question:
Does SARS-CoV-2 infection predict worsening cardiometabolic risk factors?

Methods:
Using data from OneFlorida+ (a PCORnet CRN), we compared changes over time in body mass index (BMI), systolic blood pressure (SBP) and low-density lipoprotein (LDL). We compared an Exposed cohort with a positive SARS-CoV-2 test or COVID-19 diagnosis code between March 2020 - January 2022 (n = 75,217; age: 48.5 y, 64% female), relative to a contemporary Unexposed cohort of adult patients with negative SARS-CoV-2 tests (n = 240,575; age: 52.7 y, 61% female), and an age/sex-matched Historical control cohort (March 2018 - January 2020; n = 75,217; age: 48.5 y, 64% female). We used multiple imputation for missingness in demographic and clinical factors and inverse probability weighting for confounding and loss to follow-up. We used doubly robust marginal structural models to estimate baseline and longitudinal differences in cardiometabolic indicators by cohort.

Results:
At the start of the follow-up period, adjusted for covariates and relative to the Exposed, the Unexposed (BMI: -0.5 [-0.6,-0.4] kg/m
2
, SBP: -0.5 [-0.8,-0.2] mmHg, LDL: -7.7 [-14.5, -1.0] mg/dL) and Historical control (BMI: -0.4 [-0.5,-0.3] kg/m
2
, SBP: -1.0 [-1.5,-0.6] mmHg, LDL: 12.5 [-58.3, 83.3] mg/dL) cohorts had better cardiometabolic profiles (
Figure
). Relative to changes in the Exposed, control cohorts displayed faster decreases in BMI (Unexposed only), slower increases in SBP, and no changes in LDL during the follow-up period.

Conclusions:
SARS-CoV-2 infection was associated with weight retention and a rise in blood pressure. Longer follow-up can help identify stability and impacts of these cardio-metabolic indices on events and mortality.
Abstract 15406: Loss of Estrogen Receptor α Inhibits Angiogenic Function in Right Ventricular Endothelial Cells (RVECs)
Authors: Li Jiajun , karoor vijaya , Frump Andrea L , Lahm Tim
Published: December 2023

Introduction:
Right ventricular failure (RVF) is the leading cause of death in patients with pulmonary hypertension (PH). While the pathophysiology of RVF is complex and multifactorial, insufficient angiogenesis and impaired RV endothelial cell (RVEC) function have been identified as key contributors. 17β-estradiol (E2), the most abundant female sex steroid, exerts RV-protective effects including stimulation of angiogenesis. However, the mechanism underlying E2’s pro-angiogenic function are unknown.

Hypothesis:
Estrogen Receptor (ER) α is necessary for RV angiogenesis.

Methods:
To identify the role of ERα in RVEC function and RV angiogenesis, ERα loss-of-function mutant (ERα
Mut
) rats were generated by CRISPR-Cas9.
In vivo
studies were performed in both male and female wild-type (WT) and ERα
Mut
rats. RV capillary density was assessed by immunofluorescence. RVECs were isolated from male or female WT and ERα
Mut
rats. Angiogenic function was evaluated by matrigel tube formation assay at 10h. RVEC proliferation (at 24h) was measured by Incucyte image-based analysis and Thymidine incorporation assay. RVEC migration (at 24h) was examined by transwell migration assay. Angiogenesis mediators in RVECs were quantified via Western Blot. P<0.05 was considered significant.

Results:
Female WT rats exhibited increased RV capillary density compared to males (p<0.001). However, loss of functioning ERα decreased RV capillary density (p<0.05). Loss of ERα impaired proliferation (24h) capability in female, but not male, RVECs (p<0.001). On the other hand, male, but not female, ERα
Mut
RVECs exhibited reduced cell migration in response to VEGF-A (p<0.01). Loss of ERα reduced RVEC tube formation in both sexes (p<0.05). At a molecular level, male ERα
Mut
RVECs expressed less VEGF-A, angiopoietin-2, and Id1 than WT (p<0.01) .

Conclusions:
ERα is necessary for RVEC angiogenic function. However, ERα effects on angiogenesis are sexually dimorphic. Male ERα
Mut
RVECs exhibit reduced cell migration potential and less angiogenesis mediators, whereas female ERα
Mut
RVECs exhibit decreased proliferation potential
in vitro
and reduced female RV capillary density
in vivo
. Targeting ERα may allow for sex-specific therapies aimed at enhancing RV adaptation in PH.
Abstract 15440: Efficacy of Statins in Counteracting Anthracyclines and/or Trastazumab-Induced Cardiotoxicity: A Systematic Review and Meta-Analysis With Trial Sequential Analysis
Authors: Soliman Youssef , Mouffokes Adel , Amer Basma E , Hendi Nada Ibrahim , Ramadan Alaa , Abozaid Ahmed M , Magdy Daniel John , yasen noha , Nasr Ahmed , Hassaballa Hatem
Published: December 2023

Aim:
Statins have been suggested as potential agents for mitigating chemotherapy-induced cardiotoxicity, particularly in the context of anthracyclines and/or trastuzumab treatment. However, conflicting findings have emerged from randomized controlled trials (RCTs) and observational studies. Therefore, the primary objective of this study is to comprehensively investigate the effectiveness of statins in ameliorating chemotherapy-induced cardiotoxicity in the case of anthracyclines and/or trastuzumab.

Methods:
We conducted a systematic search in major databases, including PubMed, Scopus, Web of Science, and Cochrane, up to May 10, 2023. Our main outcomes were the risk ratio (RR) of cardiotoxicity and the mean difference (MD) in left ventricular ejection fraction (LVEF%). We performed Trial Sequential Analysis (TSA).

Results:
A total of 9 studies (6 observational and 3 RCTs) were included. Although the pooled results from all studies favored statins in the incidence of cardiotoxicity (RR 0.54, 95% CI [0.37, 0.79]), evidence from RCTs only (n = 2) did not indicate any significant change in risk (RR 0.50, 95% CI [0.17, 1.45]). Similarly, while the overall change in LVEF% was significant when pooling all studies (MD 4.38, 95% CI [0.41, 8.35]), RCTs only (n = 3) showed no significant change (MD 3.94, 95% CI [-1.07, 8.96]). The TSA curve for RCTs evaluating LVEF% did not cross the conventional boundary for statistical significance, indicating that the cumulative evidence did not reach the predefined level of statistical significance threshold, with no strong evidence to establish a statistically significant relationship.

Conclusion:
The effectiveness of statins in mitigating chemotherapy-induced cardiotoxicity remains inconclusive, and the current evidence from randomized controlled trials does not demonstrate significant associations. Further research is necessary to clarify the role of statins in chemotherapy-induced cardiotoxicity.
Abstract 15494: Racial and Ethnic Differences in Cardiovascular Health Among US Adults With a History of Cancer
Authors: Cho So Mi J , Oren Ohad , Koyama Satoshi , Honigberg Michael C , Hornsby Whitney , Peloso Gina , Natarajan Pradeep
Published: December 2023

Introduction:
Evidence reports co-occurring risk factors between cardiovascular disease (CVD) and cancer and treatment-resultant cardiotoxicities amplifying CVD risks.

Hypothesis:
Given demographic disparities in CVD and cancer outcomes, we illustrated race and ethnicity-specific distributions of cardiovascular health (CVH) and quantified the contributions of socioeconomic factors to racial disparities in CVH among those with prior cancer.

Methods:
In the National Health Examination and Nutrition Survey 2011-2020, we identified 2628 adults aged ≥18 years with prior cancer. CVH was assessed based on the American Heart Association’s Life’s Essential 8 metrics. The Kitagawa-Blinder-Oaxaca decomposition quantified the magnitude of individual socioeconomic factors contributing to racial differences in CVH.

Results:
Of the 2628 US adults with prior cancer (mean[SD] age, 63.4[13.8] years; 57% women), 6.0% identified as Hispanic or Latino, 1.6% as non-Hispanic (NH) Asian, 5.2% as NH Black or African American, 84.1% as NH White, and 3.1% as uncategorized or multiple categories. NH Asian had the highest Life’s Essential 8 score (out of 100, women: 66.0; male: 69.2) in contrast to the poorest CVH in NH Black women (59.0) and Hispanic men (57.7). Overall, diet, physical activity, and body mass index were suboptimal. Across race, NH Black had the poorest blood pressure (women: 52.6, men: 41.8) and sleep (women: 74.3, men: 70.2), whereas uncategorized or multiracial group had high tobacco exposure (women: 43.6; men: 53.2). NH White women had the worst lipids (62.4), whereas NH Asian women (65.2) and Hispanic men (69.0) had the lowest glycemic score. Differences were partly explained by deprivation and low education contributing to poorer CVH among Hispanic and NH Black, whereas lower US nativity contributed to better CVH in NH Asian.

Conclusions:
CVH in US adults with prior cancer was suboptimal with significant racial disparities explained by socioeconomic factors.
Abstract 15497: Association of Blood Cell-Based Inflammatory Markers and C-Reactive Protein With Mortality in Acute Coronary Syndrome Patients: Analysis From the ATLAS ACS-TIMI 46 Trial
Authors: Chi Gerald , Jiang Ginger , Bahit Cecilia , Korjian Serge , Allaham Laith , Barnathan Elliot S , Plotnikov Alexei , Gibson Charles
Published: December 2023

Background:
Inflammation has been implicated in the pathogenesis of acute coronary syndrome (ACS). The comparative performance of blood cell-based inflammatory markers in mortality prediction among ACS patients remains unclear.

Methods:
In this multinational, double-blind, phase 2 trial, patients with recent ACS were randomized to receive rivaroxaban or a placebo. The relationship of inflammatory markers (including neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], lymphocyte-to-monocyte ratio [LMR], systemic immune-inflammation index [SII], and C-reactive protein [CRP]) with 6-month all-cause mortality was assessed using logistic regression, and the optimal cut points were determined by the Youden index. The discriminative performance of the combinations of inflammatory markers was compared by the
c
statistic.

Results:
A total of 2918 patients were analyzed. A higher risk of mortality was observed in patients with elevated NLR (≥3.691; OR=3.732; 95% CI=1.930 to 7.217; p<0.0001), elevated PLR (≥14.18; OR=2.915; 95% CI=1.447 to 5.873; p=0.0028), decreased LMR (<3.125; OR=3.179; 95% CI=1.643 to 6.152; p=0.0006), elevated SII (≥875.7; OR=2.494; 95% CI=1.285 to 4.840; p=0.0069), or elevated CRP (≥26 mg/L; OR=3.435; 95% CI=1.771 to 6.662; p=0.0003). The discriminative capacity of CRP plus NLR (c statistic=0.7326) was greater than CRP or NLR alone (c statistic=0.6444 and 0.6443) but not significantly affected by further inclusion of PLR, PLR plus SII, or PLR plus SII plus LMR into the model (c statistic=0.7430, 0.7412, and 0.7406) (Figure 1).

Conclusion:
NLR calculated from differential white blood cell count provides incremental prognostic value to CRP in predicting mortality among ACS patients. Future studies may consider NLR and CRP conjunctively in constructing mortality risk assessment models.
Abstract 15504: Impaired Branched-Chain Amino Acid Catabolism is Associated With Chemotherapy-Induced Heart Failure and Rescued by Metformin
Authors: Cheng Feixiong , Lal Jessica , Hou Yuan , Smith Jonathan D , Van Wagoner David R , Collier Patrick H , Chung Mina K
Published: December 2023

Introduction:
Heart failure resulting from cancer therapies represents a major cause of morbidity in cancer survivors. Interventional strategies to prevent and treat heart dysfunction in cardio-oncology patients continue to remain a challenge.

Hypothesis:
We posit that Branched-Chain Amino Acid Catabolism (BCAA) catabolism dysfunction is a likely causal mechanistic pathway in the pathogenesis of CTHF.

Methods:
In this study, we leveraged
electronic health records
, human-induced pluripotent stem cell (
iPSC
)-derived cardiomyocyte model-based mechanistic studies, murine models, and network medicine-basedtranscriptomics analytic methodologies, to suggest that rescuing BCAA catabolic dysfunction is a promising approach for managing chemotherapy-induced heart failure, using doxorubicin as a prototypical example.

Results:
In our large-scale cardio-oncology cohort, we observed a significant incidence of heart dysfunction and abnormal NT-proBNP levels among patients treated with doxorubicin. Using murine heart failure models, we identified significant correlations between the abundance of branched-chain amino acids (isoleucine, leucine, and valine) and cardiac dysfunction after doxorubicin exposure. Mechanistic observations in human-induced pluripotent stem cell (iPSC)-derived cardiomyocyte models further support impaired branched-chain amino acid (BCAA) catabolism by doxorubicin. Through metabolite-enzyme network analysis, we identified metformin as a repurposable drug capable of restoring branched-chain amino acid catabolism, thereby improving mitochondrial function. Human iPSC-based mechanistic studies revealed that metformin combined with doxorubicin resulted in improved insulin signaling, endothelial cell reprogramming, increased
RARA
gene expression (a key doxorubicin-induced heart failure GWAS gene) and reduced pro-fibrotic signaling. Furthermore, we demonstrate that metformin improved murine cardiac function following doxorubicin exposure.

Conclusions:
Our findings utilized electronic health records, iPSC-based mechanistic studies, and murine models to suggest that BCAA catabolic dysfunction may be a promising approach for managing chemotherapy-induced heart failure.
Abstract 15511: Predictors of Polymorphic Ventricular Tachycardia and Ventricular Fibrillation in Patients With Stress Cardiomyopathy
Authors: Chedid Maroun , Buda Kevin , Simegn Mengistu , iqbal omer
Published: December 2023

Introduction:
Polymorphic ventricular tachycardia (PVT) and ventricular fibrillation (VF) are life-threatening complications of stress cardiomyopathy (SCM) that occur in 2-10% of patients with SCM.

Hypothesis:
To identify which social and medical factors are associated with an increased risk of PVT and VF in patients with SCM.

Methods:
All consecutive patients meeting the InterTAK (international takotsubo) diagnostic criteria for stress cardiomyopathy at the Hennepin County Medical Center between January 1
st
, 2010, and December 31
st
, 2022, were identified from electronic medical records. Logistic regression was used to estimate the odds ratios (OR). The receiver operating characteristic curve (ROC) was plotted to identify the best QTc cutoff at admission to predict ventricular arrhythmia.

Results:
A total of 296 patients were included in the study, of which 27 (9.1%) experienced PVT/VF. Baseline demographics, including gender, race, and age at diagnosis, were similar to patients without PVT/VF (median age 61 years, and 66.7% were females). Patients with PVT/VF were more likely to have a history of stimulant use (22.2% vs. 8.2%, OR =3.20 p =0.023), apical (Takotsubo) variant stress cardiomyopathy (78% vs.56%, OR=2.69 p=0.038), and an ejection fraction (EF) of less than 30% on admission (63% vs. 41.5%, OR=2.39 p=0.032) (
Table 1
). Admission QTc interval cut-off value of 490 msec had the highest sensitivity and specificity in predicting the risk of ventricular arrhythmia (AUC=0.687). Notably, all PVT/VF events occurred within 17 hours of hospital admission.

Conclusion:
Nealy 1 in 10 patients with SCM had life-threatening ventricular arrhythmia. The presence of severe LV systolic dysfunction, recent stimulant use, apical variant SCM, or prolonged QTc > 490 msec is associated with the occurrence of PVT/VF, with the first day of hospital admission being an especially high-risk period.