bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10514: Compromised Cerebral Artery Integrity is Associated With Brain Tissue Injury and Cognition Deficits in Adolescents With Complex Congenital Heart Disease
Authors: Pike Nancy A , Roy Bhaswati , Cabrera-Mino Cristina , Shao Xingfeng , Halnon Nancy J , Lewis Alan B , Wang Danny , Kumar Rajesh
Published: June 2023

Introduction:
Adolescents with complex congenital heart disease (CCHD) show brain tissue injury in regions associated with cognitive deficits. Alteration in cerebral artery integrity (CAI), as measured by arterial transit time (ATT), may lead to perfusion deficits, and be a potential cause of brain injury in CCHD. To date, there are no reports of CAI in CCHD or associations between CAI, brain tissue integrity, and cognition in CCHD.

Methods:
70 subjects (37 CCHD / 33 controls), 14-18 years of age, undergone surgical palliation (CCHD), and no contraindications for a magnetic resonance imaging (MRI) and healthy controls (age- and sex-matched) participated. Participants completed cognitive testing (Montreal Assessment of Cognition [MoCA] and the Wide Range Assessment of Memory and Learning [General Memory Index, GMI]) and brain MRI using 3.0 Tesla scanner. ATT values (via diffusion-weighted pseudo-continuous arterial spin labeling [pCASL] procedures), and regional brain mean diffusivity [MD] (measure of tissue integrity) were computed in whole brain. Descriptive, partial correlations, and ANCOVA analyses used (covariates, age and sex).

Results:
Mean MoCA [23.1 ± 4.1 vs. 28.1 ± 2.3;
p
<.001] and GMI scores [86.8 ± 15.4 vs. 110.3 ± 14.5; p<.001] show significant cognitive deficits in CCHD compared to controls. ATT was significantly increased in CCHD vs controls (mean ± SD, sec, 1.3±0.13 vs 1.22±0.13, p=0.02), respectively, indicating compromised CAI. Partial correlations between ATT, MD values, and cognition (covariates, age and sex, p< 0.005) showed significant associations in various areas including the hippocampus, prefrontal cortices, cerebellum, frontal white matter, anterior and posterior cingulate, frontal cortex, temporal cortices, and midbrain.

Conclusion:
Adolescents with CCHD have prolonged ATTs compared to controls indicative of compromised CAI and altered cerebral perfusion. CAI is significantly associated with alterations in regional brain tissue integrity and cognitive impairment. Further evaluation is needed to test interventions to increase cerebral perfusion and to protect neural tissue.
Abstract 10541: Borderline Elevated Pulmonary Artery Pressures Not Meeting Criteria for Pulmonary Hypertension in Patients With Idiopathic Pulmonary Fibrosis is Associated With Lower Transplant-Free Survival
Authors: Patel Badar , Jesudasen Sirus J , Ash Samuel Y , Nardelli Pietro , San Jose Estepar Ruben , Harder Eileen M , Rahaghi Franck F , Waxman Aaron B , Washko George , San Jose Estepar Raul , Montesi Sydney B , Rahaghi Farbod N
Published: June 2023

Introduction:
Pulmonary hypertension (PH) in Idiopathic Pulmonary Fibrosis (IPF) is associated with poor outcomes. The hemodynamic definition of PH was revised from a mean pulmonary artery pressure (mPAP) ≥25 mmHg to >20 mmHg. We sought to explore the implications of these criteria in patients with IPF with a focus on outcomes in those with an elevated mPAP not meeting criteria for Pre- or Post-capillary PH, herein termed Borderline PH.

Methods:
We identified patients with IPF who underwent chest CT, transthoracic echocardiography (TTE), and right heart catheterization (RHC) using the Mass General Brigham Research Patient Data Repository. Medical records were reviewed to confirm the diagnosis of IPF. Established hemodynamic criteria categorized patients by PH status. Patients with elevated mPAP >20 mmHg not meeting the definition of Pre-capillary PH (PVR ≥3 Wood Units) or Post-capillary PH (PCWP ≥15 mmHg) were defined as Borderline PH. Categorical variables were assessed using Chi-squared, Continuous variables using Wilcoxon Rank-Sum, and transplant-free survival using Kaplan-Meier analysis and Gehan-Breslow-Wilcoxon test.

Results:
212 patients were identified: PH Present (n=92), Borderline PH (n=45), and PH Absent (n=75). One year from RHC, transplant-free survival was lower in patients with PH Present (n=37/92, 40%; p = 0.0002) or Borderline PH (n=20/45, 45%; p = 0.009) compared to those without PH (n=49/75, 65%) (Figure 1). Additionally, patients with Borderline PH had lower Pulmonary Artery Pulsatility Index (3.6 (3.0-6.0) vs 6.5 (4.2-10.5); p < 0.001), Pulmonary Artery Compliance (3.9 (3.2-4.6) vs 4.5 (3.4-5.8) mL/mmHg; p = 0.012), and an elevated Right Ventricular Stroke Work Index (9.9 (8.5-11.6) vs 7.3 (5.7-8.7) mmHg*mL/m
2
; p < 0.001) versus those without PH.

Conclusions:
In this retrospective study of patients with IPF, those with Borderline PH had lower rates of transplant-free survival and worse derived hemodynamics compared to those without PH.
Abstract 10553: Staged Percutaneous Coronary Intervention For Chronic Total Occlusion of Non-Infarct Related Artery: A Meta-Analysis
Authors: Lateef Noman , Ahsan Muhammad J , Ahmad Soban , Noori Muhammad Atif Masood , Latif Azka , Brown Kristen , Goldsweig Andrew M
Published: June 2023

Background:
Chronic total occlusion (CTO) of a non-infarct related artery (nIRA) is associated with adverse outcomes following acute myocardial infarction (AMI). The current study aimed to evaluate the impact of successful staged percutaneous coronary intervention (PCI) of nIRA CTO lesions on clinical outcomes.

Methods:
PubMed, EMBASE, Google Scholar and Scopus databases were queried for studies comparing outcomes between AMI patients who underwent successful staged PCI of nIRA CTO lesions (CTO PCI group) and AMI patients with medical management of nIRA CTO lesions or failed CTO PCI attempt (No CTO PCI group). The primary meta-analysis outcome was major adverse cardiovascular events (MACE). The main summary estimate was the random effects risk ratio (RR) with 95% confidence intervals (CIs).

Results:
Eleven studies (1 randomized, 10 observational) with 2,788 patients were included. Compared with the No CTO PCI group, the CTO PCI group demonstrated a lower incidence of MACE (Figure A, RR 0.55 [0.46, 0.66], p<0.001), all-cause mortality (Figure B, RR 0.47 [0.33, 0.66], p<0.001), cardiac mortality (Figure C, RR 0.4 [0.28, 0.59], p<0.001), stroke (Figure D, RR 0.38 [0.22, 0.66], p=0.0007) and heart failure (HF) hospitalization (RR 0.61 [0.41, 0.9], p=0.01). There was no significant difference in rates of any repeat revascularization (Figure E, RR 0.98 [0.69, 1.4], p=0.92) or target vessel revascularization (Figure F, RR 0.81 [0.48, 1.37], p=0.43) between the two groups.

Conclusion
In patients with AMI, staged PCI of nIRA CTO lesions was associated with a significantly lower incidence of MACE, all-cause mortality, cardiac mortality, stroke and HF hospitalization.
Abstract 10557: A Case of Cardiogenic Shock in a Woman With a Mitochondrial Cardiomyopathy
Authors: Girard Andrew A , Heindl Brittain F , Clarkson Stephen , Litovsky Silvio , Ubogu Eroboghene , Schwartzlow Coreen , Tallaj Jose
Published: June 2023

Case Presentation:
A 35-year-old woman with nonischemic cardiomyopathy, with a left ventricular ejection fraction <20% on home dobutamine, and chronic weakness was referred to our institution for heart transplantation evaluation. She was directly admitted to the hospital for suspected cardiogenic shock after her labs revealed a lactate level of 5.4 mmol/L. Her hospital course was complicated by persistently undulating lactate levels (0.2 - 8.6 mmol/L) that increased with exertion, despite normal mixed venous oxygen saturation measurements obtained from a pulmonary artery catheter. Serologic genetic testing was negative, and electromyography revealed the presence of a proximal and axial myopathy. A deltoid muscle biopsy was obtained, and genetic testing of the specimen revealed two mitochondrial deoxyribonucleic acid deletions, and electron microscopy revealed mitochondrial paracrystalline inclusions. She subsequently underwent left ventricular assist device placement and was started on carnitine, arginine, creatine, thiamine, and coenzyme Q10 supplementation. Despite left ventricular assist device placement, the patient has continued to decline due to progressive right heart failure and is currently being considered for cardiac transplantation.

Discussion:
Mitochondrial cardiomyopathy (MCM) is an alteration in cardiac structure and function caused by genetic defects of the mitochondrial respiratory chain, in the absence of other causes of heart failure. The true prevalence of MCM is unknown. Clinical manifestations in those with MCM present on a spectrum, ranging from asymptomatic cases to those with signs and symptoms typical of heart failure. Extra-cardiac features commonly include chronic weakness and fatigue. Diagnosis is made with prompt genetic testing and microscopic evaluation of a skeletal muscle biopsy specimen. Outcomes in patients who receive a left ventricular assist device are unknown and warrant further investigation.
Abstract 10563: Differences in Donor-Derived Cell-Free DNA Levels During Allograft Rejections in Hepatitis C Positive Donor Recipient Heart Transplant Patients
Authors: Usmani Ahsan , Lee Dae H , Wu Robby , Wicks Tammi , Fernandez Joel , Huang Jessica , Berman Peter , Feliberti Jason , KUMAR SIVA , Rinde-Hoffman Debbie , Oliveira Guilherme , Mackie Benjamin
Published: June 2023

Introduction:
Non-invasive quantification of donor-derived cell-free DNA (dd-cfDNA) has recently been shown to correlate with endomyocardial biopsy (EMB) for diagnosis of allograft rejection in heart transplant (HTx) patients. Hepatitis C virus-positive (HCV+) donor hearts are being more utilized with comparable survival outcomes.

Hypothesis:
The aim of this study is to evaluate the utility of dd-cfDNA monitoring in different types of rejections in recipients of HCV+ donor hearts.

Methods:
We performed a retrospective review of recipients of HCV+ donor hearts between 2018-2022 with paired dd-cfDNA/GEP and EMB results. The levels of dd-cfDNA/GEP were compared in different rejection types and no rejection for patients using non-parametric comparison. CMR ISHLT ≥ Grade 2R and AMR ≥ Grade 1 from histology were considered as allograft rejection.

Results:
There were 17 patients who underwent heart transplant from HCV+ donor heart. There was a total of 89 paired samples with dd-cfDNA and EMB. The reason for the biopsy was mostly for routine surveillance (N=68, 76.4%). There was a total of 1 case (1.1%) of grade 2 CMR and 16 cases of pAMR (18%; 10 cases of grade 1, 6 cases of grade 2). Levels of dd-cfDNA were elevated in cases of AMR when compared to no rejection (Median: 0.24% vs. 0.12%, respectively, P<0.001; Figure 1A). There were 57 samples (78%) with dd-cfDNA reference values of <0.12%. In patients with no rejection, dd-cfDNA levels were all below 0.25%. The AUC for elevation of dd-cfDNA and allograft rejection was 0.85 [95% C.I.: 0.72-0.97; P<0.001; Figure 1B].

Conclusions:
Non-invasive quantitation of dd-cfDNA levels is elevated in allograft rejection as assessed by traditional microscopy from EMB. There was no false-positive rate of dd-cfDNA in allograft rejection at a threshold of 0.25%. Further studies are indicated to study whether dd-cfDNA levels transiently increase only in the setting of allograft rejection or active hepatitis C viremia at the time of biopsy.
Abstract 10581: Sustained Increase of Serum Glial Fibrillary Acidic Protein After First St-Elevation Myocardial Infarction
Authors: Traub Jan , Grondey Katja , Gassenmaier Tobias , Schmitt Dominik , Fette Georg , Frantz Stefan , Boivin-Jahns Valerie , Jahns Roland , Stoerk Stefan , Stoll Guido , Weber Martin , Frey Anna
Published: June 2023

Introduction:
Acute ischemic cardiac injury predisposes for cognitive impairment, dementia and depression. Beyond altered cerebral blood flow and neurohumoral activation, recent positron emission tomography data pathophysiologically suggest acute and chronic neuroinflammation, which is accompanied by astroglial activation, after acute experimental myocardial infarction (MI).

Hypothesis:
Peripheral serum biomarkers indicating neuronal and glial involvement are altered in the year after first acute MI.

Methods:
Within the investigator-initiated, prospective, multicenter diagnostic ETiCS study, we quantified serum levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) using ultra-sensitive molecular immunoassays serially in the year after first ST-elevation MI (STEMI). Cardiac magnetic resonance imaging enabled precise detection of infarction volume and ejection fraction.

Results:
Sufficient biomaterial was available from 45 STEMI patients (aged 28 to 78 years, median 56 years, 11% female). Median serum NfL (quartiles) at hospital admission was 10.6 (7.2, 14.8 pg/ml) and median GFAP 63.8 (47.0, 89.9 pg/ml). Absolute levels of NfL (ρ=0.78; p<0.001) and GFAP (ρ=0.56; p<0.001) correlated to patient age at all time-points. While NfL remained unaltered in the course of one year, GFAP after STEMI increased in the first 3 months after MI with a mean change of +10.6±25.0 pg/ml (p=0.007), and remained elevated after 6 months (+12.4±32.9 pg/ml; p=0.015) and 12 months (+12.6±31.2 pg/ml; p=0.010) compared to baseline. Larger relative infarction volume (ρ=0.41; p=0.009) and higher peak creatine kinase levels (ρ=0.39; p<0.001), but not ejection fraction, correlated to increases of GFAP and NfL, respectively.

Conclusions:
Our findings suggest subtle glial damage after STEMI which correlates to infarction volume. Further studies need to evaluate the valence of serum GFAP as a peripheral biomarker of cognitive decline after MI.
Abstract 10584: Nerve Growth Factor/Tropomyosin Receptor Kinase A Axis Plays a Pivotal Role in Breast Cancer Progression After Myocardial Infarction
Authors: Tani Tetsuya , Oikawa Masayoshi , Misaka Tomofumi , Ishida Takafumi , Takeishi Yasuchika
Published: June 2023

Background:
Several studies have shown that cancer incidence is increasing in patients with chronic heart failure. We have reported that nerve growth factor (NGF) plays a pivotal role in sympathetic nerve remodeling after myocardial infarction (MI). However, the impact of NGF on cancer progression in the setting of MI-induced heart failure remains to be elucidated.

Methods and Results:
NGF phosphorylated tropomyosin receptor kinase A (TrkA) in murine breast carcinoma 4T1 cells, and NGF increased the percentage of Ki-67 positive 4T1 cells. MI was induced by permanent ligation of the left anterior descending artery of female Balb/c mice. Then, 4T1 cells were injected into the right fourth mammary fat pad at two weeks after MI surgery. Serum levels of NGF were higher in the MI group than in the sham group at the time of 4T1 cell injection (279±107 pg/ml vs. 172±36 pg/ml, P=0.014). The size of breast cancer was significantly larger in the MI group than in the sham group at three weeks after 4T1 cell injection (451.8±137 mm
3
vs. 304.3±136 mm
3
, P=0.0014, figure). The percentage of Ki-67 positive cells in cancer tissue was higher in the MI group compared to the sham group (37.1±6.8% vs. 16.5±3.2%, P<0.001). Furthermore, membranous TrkA was more phosphorylated in the MI group than in the sham group (1.56±0.11 AU vs. 1.00±0.11 AU, P<0.001). Knockdown of TrkA with siRNA in 4T1 cells suppressed the increase of Ki-67 positive cells by NGF stimulation (51.9±1.2% vs. 24.9±3.7%, P=0.044). A TrkA inhibitor, GW441756, suppressed the NGF-induced phosphorylation of TrkA in 4T1 cells. Moreover, the percentage of Ki-67 positive cells in cancer tissue was lower in the MI mice treated with a TrkA inhibitor (10 mg/kg/week, I.P.) than in the MI mice without a TrkA inhibitor (26.3±3.6% vs. 45.6±3.7%, P<0.001).

Conclusion:
Increased NGF caused by MI is associated with breast cancer progression through NGF/TrkA axis.
Abstract 10590: Detection of Cardiac Attr Amyloidosis in a Real-World Hf Population by Natural Language Processing Guided Automated Data Extraction From Electronic Health Records
Authors: Beles Monika , Hens Dries , Masuy Imke , verstreken sofie , Heggermont Ward , Dierckx Riet , Bartunek Jozef , Vanderheyden Marc
Published: June 2023

Background:
As cardiac aTTR amyloidosis(aTTR-CM) is frequently underdiagnosed and missed, improved screening to enhance earlier diagnosis of the disease is essential. Recent observations have demonstrated that clinical clues related to the presence of aTTR-CM and additional predisposing or associated medical conditions derived from machine learning(ML) models may provide a systematic framework to increase the suspicion of aTTR-CM in heart failure(HF) pts.
Objectives:
The present study was set up to explore the use of a systematic framework to diagnose aTTR-CM in a real-world HF population.

Methods:
Between 2014 and 2018, 3035 HF pts (Age:74 ± 12 years; EF: 45 ± 19 %, male: 50 %) consecutively referred to a community HF clinic were assessed. Using targeted disease-specific electronic health record (EHR) models (Natural language processing/ LynxCare Inc., Leuven, Be) the prevalence and odds ratios for cardiac, non-cardiac, and combinations of both cardiac and non-cardiac phenotypes predictive for aTTR-CM were assessed.

Results:
101 pts((Age: 78.57 ± 9.17 years; EF 46 ±15 %, male: 40% ) were diagnosed with aTTR-CM. Besides HF and cardiomyopathy-related phenotypes, atrial fibrillation was the strongest cardiac predictor for aTTR-CM(prevalence:76 %, OR 2.95, 95% CI= 2.10, 4.14) whereas the strongest non-cardiac predictor was carpal tunnel syndrome(prevalence :21 %, OR 6.55, 95% CI= 7.21, 5.90). The combination of heart block, joint disorders, and combined systolic and diastolic HF was the highest combined phenotype in aTTR-CM(prevalence:16 %, ORR 2.63, 95% CI = 0.96, 3.28).

Conclusion:
On top of well-known diagnoses and phenotypes unique combinations of cardiac and non-cardiac phenotypes predict aTTR-CM In a real-world HF population. Therefore, if successfully employed in the EHR this strategy may identify aTTR-CM pts and lead to earlier detection of it by raising the suspicion of the diagnosis in HF pts.
Abstract 10593: Resting Energy Expenditure is an Important Factor to Predict Cardiac Mortality in Chronic Heart Failure
Authors: Sato Takamasa , Yoshihisa Akiomi , Ishida Takafumi , Takeishi Yasuchika
Published: June 2023

Introduction:
Parameters derived from cardiopulmonary exercise testing (CPET) with respiratory gas analyzer are important prognostic factors in patients with chronic heart failure (CHF). However, all patients with CHF cannot undergo CPET for reasons such as frailty and comorbidity. On the other hands, resting energy expenditure (REE) derived from respiratory gas analyzer can be easily measured in most patients with CHF, but clinical significance of this parameter had not been fully elucidated in patients with CHF.

Aims:
We aimed to determine the clinical importance including the prognostic impact of REE in patients with CHF.

Methods:
A total of 1185 consecutive CHF patients who underwent CPET were enrolled. REE was calculated by Weir's formula (3.941resting oxygen consumption (VO
2
)+1.106resting carbon dioxide production (VCO
2
)). The study population was divided into two groups according to median REE and we compered the clinical characteristics between two groups. Also, we examined the value of REE to predict cardiac mortality in CHF patients.

Results:
In all subjects, 966 were males, median age was 63 years. Median resting VO
2
was 236 ml/min, median resting VCO
2
was 222 ml/min and median REE was 1178 kcal/day. Patients with low REE (<1178 kcal/day) were older and had higher prevalence of female and anemia, lower body mass index (BMI), more impaired renal function, lower parameters of nutrition such as serum total protein and albumin, higher levels of plasma type-B natriuretic peptide, lower resting VO
2
, lower resting VCO
2
and lower peak VO
2
than those with high REE (>1178 kcal/day). But left ventricular ejection fraction was similar between two groups. Patients with low REE had significantly higher rates of cardiac death, all cause death and composite cardiac event (cardiac death and re-hospitalization due to worsening heart failure). Furthermore, REE was the independent predictor of cardiac death, all-cause death and composite cardiac events in the Cox proportional hazard analysis after adjusted cofounding variables including peak VO
2
.

Conclusions:
REE as well as peak VO
2
is important predictor of cardiac mortality in patients with CHF.
Abstract 10615: The Effects of Maternal Hypothyroidism on Progeny Cardiac Development and Disease Susceptibility
Authors: Li Yijia , Yang Yijun , Johnson Jaslyn , Foster Michael , KUBO Hajime , Berretta Remus , Chen Xiongwen , CHen Xiongwen , Houser Steven R
Published: June 2023

Introduction:
Maternal hypothyroidism (MH) is a common clinical condition with high prevalence. MH is thought to have adverse effects on progeny's cardiac development and disease susceptibility.

Hypothesis:
MH impacts progeny's postnatal cardiac development and the susceptibility to adverse cardiac disease responses as adults.

Methods:
MH model was induced by thyroidectomy (TX) with total thyroxine (TT4) under 1ng/dl after surgery. Offspring of mice that underwent TX or Sham surgery was termed THD (Deficient) and THN (Normal) animals. Hearts were collected from THD and THN animals to determine heart weight, cardiomyocyte (CM) size, and CM proliferation. Transverse Aortic Constriction (TAC) was performed to induce pressure overload-induced cardiac hypertrophy and/or heart failure (HF) model in adult THD and THN mice. ECHO (in-vivo) and histological (in-vitro) were performed at specific times after TAC. RNA-seq was performed at embryo day (E) 18.5 and Postnatal day 5 (P5) using heart tissue.

Results:
The postnatal TT4 level was not different between the THD and THN mice. The heart weight (HW) to body weight (BW) ratio was similar between the two groups on P7, P14, and P60, but the THD mice had larger CM sizes. EdU+, Ki67+, and PH3+ CMs were lower in THD progenies on P0, P5, and P13. RNA-seq data showed that the genes related to cell division and DNA replication were downregulated in THD mice on E18.5 and P5, respectively. In adult animals six weeks after TAC, the THD mice had a greater HW/BW ratio and lung weight(LW) to BW ratio, consistent with more severe cardiac hypertrophy and HF than the THN mice. After TAC, THD mice had a lower LVEF, higher absolute E/e' ratio, greater end-diastolic pressure, and more severe LV fibrosis than THN mice.

Conclusions:
Alterations in CM proliferation during fetal and early postnatal development results in fewer adult CMs in animals from MH mothers. These changes are associated with increased disease susceptibility in adult MH progeny.
Abstract 10618: Modified Rna Ccnd2 Promotes Myocardial Remuscularizationin Lv Infarct by Regulating Cardiomyocyte Cell Cycle
Authors: Wang Lu , Sun Jiacheng , Zhou Yang , Wei Yuhua , Zhang Jianyi J
Published: June 2023

The adult mammalian heart has limited capacity to regenerate, due to postnatal cardiomyocyte cell cycle arrest. This study examined whether the cardiomyocyte cell-cycle reactivation can enhance myocardial remuscularization in hearts with acute myocardial infarction (AMI). Because the G1-to-S phase transition of the cell cycle is critically regulated by cyclin D proteins, and the expression of cyclin D2 (CCND2) could regenerate injured myocardium, we hypothesized that a transient and exclusive overexpression of CCND2 in cardiomyocytes can result in myocytes proliferation and therefore, remuscularize myocardial infarct. The transient and exclusive myocyte overexpression of CCND2 was achieved by Specific ModRNA Translation system (SMRTs)
1
.
In vitro
assessments were performed in hiPSC-derived cardiomyocytes (hiPSC-CMs) by immunofluorescence staining of cell proliferation markers (Ki67, BrdU, PH3, and Aurora B) to evaluate whether cardiomyocyte-specific modified RNA CCND2 (
CMS
modRNA-CCND2) could reactivate cell cycle. Using a mouse model of AMI, normal and infarcted mice were compared 4 weeks after AMI to assess the structural and functional outcomes of myocardial injection 100μg
CMS
modRNA-CCND2.
In vitro
, the,
CMS
modRNA-CCND2 resulted in significantly higher CMs cell cycle activity as evidenced by significantly higher percentage of hiPSC-CMs that expressed Ki67 (8.68 ± 1.64 VS 36.68 ± 2.61 , p<0.01), BrdU (8.44 ± 1.14% VS 17.59 ± 0.84%, p<0.01), PH3 (0.51 ± 0.04% VS 1.68 ± 0.09%, p<0.01), and Aurora B (0.47 ± 0.03% VS 1.59 ± 0.07%, P<0.01),
CMS
modRNA-Luciferase vs
CMS
modRNA-CCND2, respectively.
In vivo,
CMs cell cycle activity was significantly increased in SMRT treated hearts 4 weeks post AMI as evidenced by: Ki67 (0.41 ± 0.04% VS 2.00 ± 0.17%, p<0.01), PH3 (0.039 ± 0.004% VS 0.30 ± 0.006%, p<0.01), AMI VS AMI + SMRT, respectively. LV Infarct size also decreased significantly 4 weeks after AMI in AMI + SMRT group of hearts (50.04 ± 1.42% VS 31.28 ± 1.28%, p<0.01). Thus,
CMS
modRNA-CCND2 could induce myocardial remuscularization by re-activating CM cell- cycle in hearts with AMI. *, equal contribution first author
Abstract 10623: Association of Changes in Glycemic Status and Risk of Cardiovascular Disease Among Adults With Hypertension - A Post-Hoc Analysis of the Systolic Blood Pressure Intervention Trial (SPRINT)
Authors: Levy Drew , Hagan Kobina , Cainzos Achirica Miguel , Nasir Khurram , Pandey Ambarish , Patel Kershaw
Published: June 2023

Introduction:
Prediabetes (preDM) is a risk factor for diabetes mellitus (DM) and both are associated with elevated risk of cardiovascular disease (CVD). However, the association of transitions in glycemic status with cardiovascular disease (CVD) is not well established.

Methods:
The present study included participants with hypertension enrolled in the Systolic Blood Pressure Intervention Trial (SPRINT) without DM at baseline. Study participants had available fasting plasma glucose (FPG) at baseline and 2-year follow-up and no primary outcome CVD event (myocardial infarction, other acute coronary syndrome, stroke, heart failure, or cardiovascular death) prior to 2 years. Euglycemia, preDM, and DM status were defined based on FPG, self-reported history, or use of glucose-lowering medication. Participants were stratified by glycemic status at baseline and 2-year follow up. The association of changes in glycemic status with CVD risk were assessed using adjusted Cox models.

Results:
The present study included 4,708 participants (33.6% women, 35.1% Black, 41.4% preDM). Among 2,760 participants with euglycemia at baseline, 716 (25.9%) developed preDM or DM over 2-year follow-up. Most participants with baseline preDM continued to have preDM or progressed to DM (71.3%). After the 2-year visit, 151 participants (3.2%) had a CVD event. Participants with persistent euglycemia had fewer CVD events (2.6%) compared with those with incident preDM or DM on follow-up (4.5%) (Figure 1A). In adjusted analysis, among participants with baseline euglycemia, those who developed prediabetes or diabetes had 70% higher risk of a CVD event during follow-up compared with those with persistent euglycemia (HR [95% CI], 1.70 [1.09-2.64]) (Figure 1B).

Conclusions:
In adults with hypertension, worsening glycemic status from euglycemia to preDM or DM was associated with higher risk for CVD. Prevention of dysglycemia may be an important target to prevent CVD in hypertension.
Abstract 10679: Do Hospitals Caring for a High Proportion of Black Adults Deliver Lower Quality Care for Heart Failure? An Analysis of the Get With the Guidelines-Heart Failure Registry
Authors: Diamond Jamie E , Ayodele Iyanuoluwa , Joynt Maddox Karen E , Yeh Robert W , Fonarow Gregg C , Allen Larry A , Greene Stephen J , Devore Adam D , Chiswell Karen , Yancy Clyde W , Wadhera Rishi
Published: June 2023

Introduction:
Black individuals have higher hospitalization and mortality rates from heart failure (HF). Black adults receive care at a limited set of US hospitals (minority-serving hospitals [MSH]) and understanding quality of care at these sites could inform efforts to improve health equity. Using the Get With The Guidelines (GWTG) - HF Registry, we compared HF care quality and clinical outcomes at MSH vs. non-MSH.

Methods:
We identified adults ≥18 years hospitalized for HF at GWTG-HF sites. MSH were defined as the top quintile of proportion of hospitalizations for Black adults. We compared performance on GWTG-HF quality measures at MSH vs. non-MSH, adjusting for age, sex, comorbidities, and hospital characteristics, using GEE to account for clustering within sites. After restricting to adults ≥65 years and linking to Medicare FFS claims, we used multivariable Cox proportional hazard models to compare post-discharge outcomes.

Results:
Study population included 422,483 hospitalizations at 480 hospitals, of which 96 (with >38% Black patients) were MSH. Care quality was similar between MSHs and non-MSHs for 10 of 13 GWTG-HF measures; MSH patients were less likely to be discharged with 7-day follow up, CRT device planning, or aldosterone antagonist
(Figure).
Overall defect-free care was similar across sites; there were no within-hospital disparities between Black vs. White patients at both MSH and non-MSH. Among 111,930 Medicare beneficiaries, risk-adjusted 30-day readmissions were higher at MSH compared with non-MSH (HR 1.14, 95% CI 1.02-1.26), but risk-adjusted 30-day mortality was similar (HR 0.92, 95% CI 0.84-1.02).

Conclusions:
Across GWTG-HF-participating hospitals, HF care quality and mortality were similar at MSH vs. non-MSH, but MSH 30-day readmissions were higher. Improving MSH post-discharge follow-up could improve equity in HF outcomes, though additional investigation to address higher MSH readmissions is needed.
Abstract 10683: Alternations in Autonomic Function During Pulmonary Vein Isolation Without Targeting Ganglionated Plexi Ablation in Patients With Atrial Fibrillation
Authors: Hamaoka Takuto , Luck Jonathan C , Gonzalez Mario , Cui Jian
Published: June 2023

Introduction:
Abnormal autonomic innervation in the left atrium was reported to be related to developing/sustaining atrial fibrillation (AF). Autonomic denervation by radiofrequency catheter ablation (RFCA), evaluated by heart rate variability (HRV), is associated with a lower recurrence rate of AF. Ganglionated Plexi (GP) has been regarded as a target of autonomic denervation during the RFCA; however, the degree by which autonomic function is altered during the RFCA procedure remains unclear. Hypothesis:We tested the hypothesis that autonomic function is altered consistently during the ablation procedure without targeting GP.

Method:
Thirteen patients with paroxysmal AF who underwent pulmonary vein isolation (PVI) via RFCA were included (Age, 64.3 ± 1.9; Male/Female, 10/3). PVI was performed in the order prescribed (left superior, left inferior, right superior, and right inferior PV). HRV was assessed prior to, during each PV ablation, and post-ablation.

Results:
A vagal response (significant bradycardia) during the procedure was observed in three patients. The parameter of para-sympathetic nerve activity (para-SNA) (e.g., RMSSD, 38.7 ± 7.8 vs. 26.6 ± 6.0 ms, P < 0.05), and total power of HRV (1861 ± 831 vs. 1105 ± 584 ms, P < 0.05) were decreased by the procedure. While the balance of SNA to para-SNA (ratio of low to high frequency, LF/HF) was unchanged, which may indicate both SNA and para-SNA denervation. Using a linear mixed effect model, the effect of the “period” (i.e., pre, each PV, post) on the reduction in para-SNA parameter (HF) or total power of HRV was significant (both, P < 0.05). The reduction was consistent in each PV, and post-hoc analysis (Bonferroni) showed significant differences only between baseline and post-RFCA in these parameters (P < 0.05). Even in the patients without significant bradycardia response, the reduction in HRV parameter was significant in the linear mixed effect model (e.g., the effect of the “period” on RMSSD, P < 0.05).

Conclusion:
We found that the PVI by RFA, without targeting GP, modified autonomic function, even in the patients who did not develop vagal responses. The HRV change was consistent during each PV isolation, which may suggest the non-necessity of GP ablation for autonomic modification by the ablation.
Abstract 10747: Left Atrial Volume Index is Associated With New-Onset Heart Failure Admission and Cardiovascular Death in Patients With Asymptomatic Moderate Aortic Stenosis
Authors: Maeda Mika , Omori Taku , Kuwajima Ken , Shiota Takahiro
Published: June 2023

Background:
Left atrium enlargement is the marker of increased left ventricular (LV) filling pressure and morphological indicator of chronically increased hemodynamic burden. However, the potential utility and clinical significance of left atrial volume (LAV) index in asymptomatic moderate aortic stenosis (AS) patients have been unknown. Therefore, we assessed the impact of LAV index on cardiovascular events in asymptomatic moderate AS patients.

Methods:
We retrospectively analyzed 549 patients (mean age 79±13 years) with asymptomatic moderate AS (mean transaortic pressure gradient 20 to 39 mmHg) and LVEF ≥50 %. Cardiovascular events were defined as cardiovascular death or admission for heart failure (HF).

Results:
During a follow-up period (median, 1301 days; range, 296 to 2179 days), 216 patients underwent aortic valve replacement (AVR) or balloon aortic valvuloplasty (BAV), and 132 HF admission and 37 cardiovascular deaths occurred. In the multivariable analysis, LAV index, lateral E/e′, and peak tricuspid regurgitation velocity were independent predictors of cardiovascular events (Hazard ratio (HR) 1.07 [1.05 to 1.09]; HR 1.04 [1.00 to 1,08]; HR 1.04 [1.00 to 1.07], respectively) after adjusting for age, female, body mass index, previous myocardial infarction, atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease, moderate mitral regurgitation, E velocity, LV hypertrophy, and surgical or transcatheter AVR or BAV. LAV index of 27 mL/m
2
was the optimal cutoff value for predicting cardiovascular events with sensitivity of 89% and specificity of 60% and C-statistics for LAV index demonstrated superiority to lateral E/e′ and peak tricuspid regurgitation velocity (
P
<0.001) (Figure).

Conclusion:
LAV index is an important predictor for cardiovascular events in asymptomatic moderate AS patients.
Abstract 10781: An Unusual Case of Transient Inflammatory Constrictive Pericarditis: IgG4 Disease
Authors: Majid Muhammad , Lak Hassan Mehmood , Yaker Zachary S , Mazumder Samia H , Agrawal Ankit , Syed Alveena , Klein Allan L
Published: June 2023

Case Presentation:
A 54-year-old male with a past medical history of hypertension presented with chest tightness, shortness of breath, fatigue, and ankle edema. His vital signs were within normal limits but physical exam was significant for jugular venous distension and bilateral peripheral edema. Laboratory studies were unremarkable except for elevated inflammatory markers (C-reactive protein [23.6 mg/dl] and erythrocyte sedimentation rate [34 mm/hour]). Interferon assay, Influenza A/B antigens and anti-nuclear antibody were negative. The patient was diagnosed with constrictive pericarditis (CP). Although the patient was treated appropriately for pericarditis with a steroid taper, colchicine and ibuprofen, his symptoms recurred. Therefore, he underwent a radical pericardiectomy which resulted in a marked clinical improvement. The final pericardial pathology revealed fibrosis and plasma cell infiltrates with >30% of cells positive for IgG4. An echocardiogram revealed a small pericardial effusion with septal bounce, annulus reversus, and a plethoric inferior vena cava consistent with a diagnosis of CP. Cardiac magnetic resonance imaging showed a small circumferential pericardial effusion and respirophasic septal flattening during inspiration with marked pericardial delayed enhancement (DHE).

Discussion:
CP is commonly caused by viral or idiopathic etiologies, with infection (tuberculosis) being more prominent in developing countries. IgG4 disease is an uncommon cause of CP with only a few cases of IgG4-related CP have been reported. Pathological findings on histology include IgG4-positive lymphoplasmacytic cells and fibrosis. The disease is characterized by steroid-responsive condition but pericardiectomy is pursued with a suboptimal response. Cardiovascular manifestations of IgG4 disease are under explored and our case illustrates the importance of recognizing and treating the pericardial complications of IgG4 disease.
Abstract 10851: A Randomized Study to Compare LDL-C-Lowering Effects of Inclisiran With Usual Care vs Usual Care Alone in Patients With Recent Hospitalization for an Acute Coronary Syndrome: Rationale and Design of the VICTORION-INCEPTION Trial
Authors: Anderson Jeffrey L , Navar Ann M , Balachander Neerja , Lecocq Jason , Desai Nihar R , Knowlton Kirk U
Published: June 2023

Introduction:
Patients are at high risk for a recurrent cardiovascular (CV) event in the first year following acute coronary syndrome (ACS). Low-density lipoprotein cholesterol (LDL-C) is a modifiable risk factor for recurrent CV events. Despite the availability of lipid-lowering therapies (LLT), many patients fail to achieve guideline recommended LDL-C <70 mg/dL in the year post-ACS. Early LDL-C evaluation and LLT intensification after recent ACS may reduce recurrent CV event risk. In prior phase III trials, inclisiran plus maximally tolerated statin therapy effectively reduced LDL-C in patients with established ASCVD. As patients with an ACS within 3 months of screening were excluded from these trials, the efficacy of inclisiran in these patients is unknown.

Objective:
To assess the LDL-C-lowering effect of inclisiran with usual care vs usual care alone in patients with recent ACS and LDL-C ≥70 mg/dL, despite statin therapy.

Methods:
VICTORION-INCEPTION (NCT04873934) is a phase IIIb, randomized, parallel-group, open-label, multicenter, US-based trial enrolling eligible patients to receive inclisiran plus usual care or usual care (
Figure
). Concomitant LLT and routine LDL-C assessment is at the discretion of the managing physician to mimic real-world clinical practice. The primary endpoints are percent change from baseline in LDL-C and proportion of patients achieving LDL-C <70 mg/dL. Key secondary endpoints include absolute change from baseline in LDL-C by visit, proportion of patients reaching pre-specified LDL-C targets, other plasma lipids, adherence to background LLT, and safety and tolerability of inclisiran. Exploratory endpoints include patient-reported outcomes and healthcare resource utilization.

Conclusions:
VICTORION-INCEPTION, an ongoing trial planned to complete in early 2024, will assess the effectiveness of inclisiran plus usual care for the management of patients with elevated LDL-C post-ACS despite receiving statin therapy.
Abstract 10860: Limb and Cardiovascular Event Risk in Type 1 and 2 Diabetic Patients With Peripheral Artery Disease
Authors: Sykora Daniel , Firth Christine , Girardo Marlene , Sarma Dhruv , Tseng Andrew S , Wennberg Paul W , Liedl David , Shamoun Fadi
Published: June 2023

Introduction:
Peripheral artery disease (PAD) is a risk factor for adverse limb events (LE) and cardiovascular events (CVE) that often coexists with type 1 (T1) and type 2 (T2) diabetes mellitus (DM), which differ mechanistically. There is a paucity of data on comparative risk of LE and CVE in T1DM and T2DM patients with PAD.

Methods:
We queried our database of 40,144 patients ≥18y old who underwent ankle brachial index (ABI) measurement from 01/1996-02/2020. We isolated patients with T1DM or T2DM and with PAD diagnosed by ABI (low [<1.0] or elevated [>1.4]). We retrieved demographics including hemoglobin A1c (A1c). Primary outcomes were LE (critical limb ischemia or vascular amputation) and CVE (myocardial infarction or ischemic stroke). All-cause mortality was a secondary outcome. Multivariable Cox proportional regression yielded hazard ratios (HR) with 95% confidence intervals (CI) after adjusting for age, sex, A1c, hypertension, hyperlipidemia, coronary artery disease (CAD), chronic kidney disease (CKD), and tobacco use.

Results:
Our study found 9,271 patients with PAD and DM (36% T1DM, 64% T2DM) with median follow-up time 34 mo (interquartile range [IQR] 85 mo). T1DM patients were younger than T2DM (mean age 67 vs 70y), with higher median A1c (7.7 [IQR 1.9] vs 6.7% [IQR 1.6]), and higher prevalence of hypertension, hyperlipidemia, CAD, and CKD. Antiplatelet and statin use did not differ. Elevated ABI was more common in T1DM (47 vs 27%). LE occurred in 23% and CVE in 12% of patients. LE risk was higher in T1DM patients than T2DM (HR 1.59[95% CI 1.45,1.74], p<0.0001), but CVE and all-cause mortality did not differ significantly.

Conclusions:
PAD patients with T1DM had a higher LE risk than those with T2DM, even after adjustment for A1c and pertinent risk factors, but CVE risk and all-cause mortality were equivocal. These data suggest a potential role for more intensive LE risk modification in PAD patients with T1DM, but further investigation is needed to minimize limb morbidity.
Abstract 10865: Reduced Right Atrial Strain is a Marker for Increased Mortality in Patients With Acute Pulmonary Embolism
Authors: Eguchi Shunsuke , Pfeiffer Michael , Peterson Brandon , Ruzieh Mohammed , Gao Zhaohui , Boehmer John , Gorcsan John , Wilson Ryan
Published: June 2023

Introduction and Hypothesis:
Evaluation of the right heart function is known to have value in assessment of patients with acute pulmonary embolism (PE). The right atrium (RA) is directly impacted by right ventricular pressures. Strain analysis is an evolving area of echocardiography, and can be applied to evaluate the RA. To date, limited studies have evaluated RA strain in the setting of PE, and we hypothesized that RA strain analysis would be prognostic of outcomes in patients with acute PE.

Methods:
We performed a retrospective cohort study of 177 patients with acute pulmonary embolism. Strain analysis was performed on echocardiograms completed within 48 hours of admission. Peak longitudinal RA strain was applied using TomTec®. The primary outcome was 30-day all-cause mortality and in-hospital mortality. Receiver operating characteristic (ROC) curves and Kaplan-Meier curves were used for evaluation.

Results:
Study quality was sufficient to perform peak longitudinal RA strain analysis in 151 patients (86.8%). In-hospital mortality was 8.9% and 30-day mortality was 12.7%. Peak longitudinal RA strain was significantly reduced in patients with all-cause death up to 30 days and in-hospital death compared to survivors (30-day mortality: 20.9% ± 4.9% vs 30.7% ± 7.8%, p < 0.001. In-hospital mortality: 21.1% ± 5.0% vs 30.1% ± 8.0%, p < 0.001). Using ROC curves, we chose a peak longitudinal RA strain value of 26.5% (sensitivity 95%, specificity 73%) for detecting all-cause mortality up to 30 days. When dividing patients into 2 groups using this cut-off value, low peak longitudinal RA strain was associated with worse prognosis (HR 33.0, 95% CI= 4.4-248.8, p < 0.001. Figure).

Conclusions:
RA strain have significant prognostic value in patients with acute PE, and identifying those at increased risk of death which may indicate the need for more aggressive treatment. Assessment of RA strain has promise for clinical applications.
Abstract 10874: Predictors of Prehospital Opiate Use in Patients With ST Elevation Myocardial Infarction: Results From a Nationwide Database
Authors: Szabo Dominika , Szabó András , Magyar Levente , Szentgroti Rita , Kiraly Adam , János Pál Bathó , Szegeczky Tibor , Kocsis Tibor , Edes Istvan Ferenc , Ruzsa Zoltan , Becker David , Merkely Bela , Szekely Andrea , Hizoh Istvan
Published: June 2023

Introduction:
Opiates are traditionally used in STEMI patients to relieve pain, decrease pulmonary congestion, and anxiety. Yet, according to in vitro measurements, they delay and diminish the effect of all currently used oral platelet P2Y12 receptor antagonists. To be able to draw causal conclusions on the potential effects of opiates on clinical outcomes using real-world registries, the bias in treatment allocation may be minimized by propensity score methods. Therefore, we constructed a simple model of prehospital opiate administration using the database of the National Ambulance Service.

Methods:
We analyzed data of 10,139 subjects who were diagnosed with STEMI within 24 hours from symptom onset between November 2018 and June 2021. Patients with unsuccessful out-of-hospital CPR were excluded. Opiates were applied in 3,992 cases (39.4%). Besides onset-to-door time and need for CPR due to OHCA, basic demographic data like age and sex were studied as candidate predictors using logistic regression. Non-linearity of the continuous predictors was assessed by restricted cubic splines. Relative importance of the predictors was characterized by the Akaike Information Criterion (AIC).

Results:
Overall model fit was good: likelihood ratio chi-square=610.40, d.f.=10, p<0.0001. Opiate use was strongly associated with onset-to-door-time (p<0.0001, AIC=333.83) and Wald testing for linearity suggested a non-linear relationship (p<0.0001) with the highest odds at about 120 minutes. Similarly, it was also highly (p<0.0001, AIC=193.78) and non-linearly (p<0.0001) related to age with an inverted U-shaped curve. Moreover, it was negatively dependent on the need for CPR (p=0.0019, AIC=7.64) and unrelated to the sex of the patient (p=0.15, AIC=0.09).

Conclusion:
Our propensity score model may help to evaluate the role of opiate administration on clinical outcomes of STEMI patients and underscores the importance of non-linear modeling of continuous predictors.
Abstract 10880: Left Atrial Epicardial Adipose Tissue Predicts Atrial Fibrillation Recurrence Following Catheter Ablation
Authors: Chahine Yaacoub , Macheret Fima , Ordovas Karen G , Boyle Patrick M , Akoum Nazem W
Published: June 2023

Introduction:
Atrial fibrillation (AF) recurrence following catheter ablation (CA) remains high. Epicardial adipose tissue (EAT) is increasingly recognized for its significant role in promoting AF arrhythmogenesis due to its proinflammatory properties and anatomic proximity to the myocardium. We sought to assess whether left atrial (LA) EAT volume is associated with AF recurrence following CA.

Methods:
EAT was assessed via cardiac MRI using a 3D Dixon sequence (Panel A) in 101 patients undergoing radiofrequency or cryoballoon CA for AF. Patients were followed for AF recurrence.

Results:
During an average follow-up period of 300 days, post ablation AF recurrence occurred in 31 (30.7%) patients. The median time for AF recurrence following CA was 136 days. LA EAT index was higher in those with recurrence (20.7 [16.9, 30.4] vs 13.7 [10.5, 20.1] mL/m
2
, p < 0.001), and so was LA volume index (66.6 [53.8, 77.5] vs 49.9 [37.7, 62.8] mL/m
2
, p < 0.001). The ROC curve for LA EAT index in the prediction of AF recurrence had an AUC of 0.77 (95% CI 0.68-0.86, p<0.001) and showed an optimal cutoff value of 14.29 mL/m
2
to identify patients at risk of AF recurrence post ablation (Youden’s J statistic = 0.446). Integrating LA EAT with clinical risk factors (age, BMI, AF type and hypertension) provided a better discriminatory performance in predicting AF recurrence than clinical risk factors alone (AUC 0.79 vs 0.65, DeLong test p = 0.044) (Panel B). Cox regression analysis showed LA EAT (HR: 1.088; 95% CI: [1.047-1.13], p <0.001) to be an independent predictor of post ablation AF recurrence. The Kaplan-Meier curve for recurrence free survival showed a significant difference between 2 groups of patients identified by the optimal LA EAT index cut-off of 14.29 mL/m
2
(log rank = 14.79; p < 0.001) (Panel C).

Conclusion:
EAT quantified using cardiac MRI, a reproducible and widely accessible imaging parameter, is a strong and independent predictor of AF recurrence following CA.