bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10234: HMGCS2-Mediated Ketogenesis Induces Adult Cardiomyocyte Dedifferentiation and Enables Cardiac Regeneration
Authors: Cheng Yuan-Yuan , Gregorich Zachery , Prajnamitra Ray P , Lundy David J , Lee Yi-Chan , Ruan Shu-Chian , Lin Po-Ju , Yan Yu-Ting , Tian Rong , Kamp Timothy J , Hsieh Patrick C
Published: June 2023

Introduction:
Human cardiac regeneration after injury is limited by the low proliferative capacity of adult mammalian cardiomyocytes (CMs). However, some animals readily regenerate lost myocardium
via
a process involving CM dedifferentiation, which unlocks their proliferative capacity.

Methods:
Inspired by this concept, we generated mice with inducible, CM-specific expression of the Yamanaka factors (OSKM), enabling adult CM dedifferentiation
in vivo
. We profiled changes in CM gene expression by microarray, measured metabolite production by LC-MS and
13
C NMR, and used adeno-associated virus (AAV) to over-express target genes. Cardiac function was measured by echocardiography and intraventricular catheterization.

Results:
Two days following OSKM induction, adult CMs exhibited a dedifferentiated phenotype and increased proliferation
in vivo
. Microarray analysis revealed alterations of metabolism-related pathways, particularly an increase of the ketogenic enzyme HMGCS2. Analysis of metabolites confirmed that HMGCS2-induced ketogenesis in adult CMs allowed a metabolic switch from fatty acid oxidation towards ketone utilization. AAV-driven overexpression of HMGCS2 in OSKM mice induced more adult CM dedifferentiation and increased the proliferation rate by two-fold compared to controls. The same phenomenon was observed after myocardial infarction, specifically in the border zone. On the contrary, CM-specific HMGCS2 knockout mice showed poorer baseline cardiac function and impaired recovery following injury. Forced expression of HMGCS2 rescued cardiac function in these mice, thus demonstrating a role of ketogenesis in CM dedifferentiation and proliferation.

Conclusions:
These data demonstrate the importance of HMGCS2-induced ketogenesis as a means to regulate metabolic response to mammalian cardiac injury, allowing cell dedifferentiation and proliferation as a regenerative response.
Abstract 10237: Targeting on Nrf2/Sesn2 Signaling to Rescue Cardiac Dysfunction During High Fat Diet-Induced Obesity
Authors: Krause-Hauch Meredith , Fedorova Julia R , Zoungrana Linda Ines , Wang Hao , Li Zehui , Fatmi Mohammad , Davitt Kayla , Ren Di , Li Ji
Published: June 2023

Introduction:
Obesity increases the chances of developing cardiovascular disease and strokes. The overabundance of adipose tissue that occurs in obese individuals increases oxidative stress, which trigger upregulation of antioxidant proteins, Sesn2 and Nrf2.

Hypothesis:
Obesity-related oxidative stress triggers cardiac Sesn2 and Nrf2 to function in cardioprotective properties.

Methods:
Cardiomyocyte specific Sesn2 knock out (cSesn2
-/-
) and overexpression (tTa-tet-Sesn2) C57BL/6J mice, and their wildtype littermates (Sesn2

f/f

and tet-Sesn2) were subjected to either a high fat diet (HFD) or chow diet. Seahorse XF Analyzer for mitochondrial function and IonOptix Calcium and Contractility System for cardiomyocytes contractile functions.

Results:
The inducible cardiomyocyte overexpression of Sesn2 (tTa-tet-Sesn2) versus tet-Sesn2 mice gained less weight with HFD. Echocardiography data showed no significant differences in systolic function between tet-Sesn2 and tTa-tet-Sesn2 with HFD or chow diet. However, HFD induced diastolic dysfunction of tet-Sesn2 but not tTa-tet-Sesn2 hearts. Intriguingly, cardiac Nrf2 levels were upregulated in tTa-tet-Sesn2 but not tet-Sesn2 hearts with HFD. Conversely, cSesn2
-/-
versus Sesn2

f/f

showed lower Nrf2 levels and greater cardiac dysfunction with HFD. MitoSOX staining demonstrated that tTa-tet-Sesn2 versus tet-Sesn2 maintain redox homeostasis in the heart with HFD, while cSesn2
-/-
versus Sesn2

f/f

showed more reactive oxygen species (ROS) in the heart with HFD. Mitochondrial respiration was impaired in obese cSesn2
-/-
versus Sesn2

f/f

cardiomyocytes. Moreover, the contractility and transient calcium flux signaling was impaired in obese cSesn2
-/-
versus Sesn2

f/f

cardiomyocytes. tTa-tet-Sesn2 versus tet-Sesn2 cardiomyocytes demonstrated resistance to HFD-induced contractile dysfunctions, impaired calcium homeostasis and activation of the inflammation-related signaling NF-κB.

Conclusions:
Sesn2 and Nrf2 modulate redox homeostasis and inflammatory response during obesity pathogenesis. There is a feedforward loop relationship between Sesn2 and Nrf2 in the heart with HFD-induced obesity. Cardiac Sesn2/Nrf2 signaling ameliorates cardiac dysfunction caused by obesity.
Abstract 10250: Association of Nutritional Status With Symptoms and Quality of Life After Aortic Valve Replacement
Authors: Niemi Heikki J , Kylmälä Minna , rajala helena , Lommi Jyri , Suihko Satu
Published: June 2023

Introduction:
Most patients with aortic stenosis (AS) are elderly and have multiple comorbidities. These conditions are often associated with poor nutrition and frailty. The purpose of this study was to assess the impact of preoperative nutritional status on symptoms and quality of life (QOL) after aortic valve replacement.

Methods:
We prospectively studied 220 patients with severe AS. Nutritional status was assessed using the Mini Nutritional Assessment (MNA) questionnaire. A score below 24 out of 30 indicates risk of malnutrition. Patients were evaluated preoperatively and three months after intervention. QOL was assessed using the RAND 36-item health survey. The six-minute walking test (6MWT) and the five times sit to stand test (5TSTS) were performed in 92 and 87 patients, respectively.

Results:
MNA score was below 24 in 28 % of the patients. Age, BMI, sex, and the proportion of patients undergoing surgery or TAVI were similar between MNA < 24 and MNA > 24 groups. There were no differences in NYHA class preoperatively, however a larger proportion of patients with MNA < 24 remained in NYHA 2 or higher after intervention (42 % vs 25 %, p = 0.03). They also remained more symptomatic, with dyspnea in 28 % vs 12 % (p = 0.01) and decreased exercise capacity in 44 % vs 16 % (p < 0.001) of the patients. Postoperative QOL was worse in patients with MNA < 24, with significant differences in seven categories (Figure). They performed worse in 6MWT at baseline (median 380 m vs 480 m, p = 0.02), but the difference was not significant after intervention (480 m vs 499 m, p = 0.4). Difference in 5TSTS was not significant at baseline (13.45 s vs 11 s, p = 0.1), but they performed worse after intervention (14.95 s vs 10.8 s, p = 0.02).

Conclusions:
Malnutrition is common among AS patients and is associated with worse QOL and more symptoms after intervention. Nutritional status should be assessed in AS patients before intervention for risk stratification and to find patients who might benefit from nutritional intervention.
Abstract 10254: Renal CD11c
+
F4/80
-
Dendritic Cells, but Not Renal CD11c
+
F4/80
+
Macrophages, Transfer the Hypertension From Angiotensin II-mice
Authors: Araos Patricio A , Cortes Sut'yam , Campos Rafael , Reyes Javier , Figueroa Stefanny , Fuenzalida Maria Jose , Pacheco Rodrigo , Amador Cristian A
Published: June 2023

Introduction:
Immune system participates in Angiotensin II (AngII)-hypertension (HTN). Previously, it was shown that dendritic cells (DCs)-CD11c
+
are required for HTN development. However, new CD11c
+
cell subpopulations, presenting macrophages (Mφ) characteristics (F4/80
+
), have been described. Since renal DCs and Mφ share several markers, their participation in AngII-HTN remains under discussion. Our objective was to analyze whether renal DCs-CD11c
+
F4/80
-
or/and CD11c
+
F4/80
+
(Mφ) modify their phenotype in the AngII-HTN, and to determine if they promote HTN by transferring this phenotype to normotensive animals.

Methods:
Male C57BI/6 mice (8-10 weeks-old, n=6) were infused with AngII (490 ng/kg/min) by 14-days. We measured systolic blood pressure (SBP), and renal DCs-CD11c
+
F4/80
-
and Mφ-CD11c
+
F4/80
+
infiltrations were evaluated by flow cytometry. In addition, these cells were isolated at 14-days and transferred to normotensive mice (n=4-5) for SBP measurements. Finally, renal Mφ-CD11c
+
F4/80
+
from HTN mice were stimulated
in vitro
with AngII (100nM-24h) to analyze the mRNAs abundance of
Nox2
,
Sgk1
,
ENaC
and

AT
1
R

, by qRT-PCR.

Results:
AngII increased SBP (AngII 134.7±6.9 vs. Vehicle (Vh) 114.5±7.8mmHg; p<0.001) and promoted the infiltration of DCs-CD11c
+
F4/80
-
(AngII=45.6±11.9% vs. Vh=31.7±6.7%; p<0.05) and Mφ-CD11c
+
F4/80
+
(AngII=66.1±8.4% vs. Vh=55.6±5.1%; p<0.05) in renal medulla. No statistical differences we observed in the renal cortex. Interestingly, the adoptive transfer of renal Mφ-CD11c
+
F4/80
+
(1x10
6
-cells) from AngII animals to healthy recipient mice did not transfer HTN after 24h (baseline=106.8.0±2.3 vs. 112.4±4.5mmHg; ns), compared to DCs-CD11c
+
F4/80
-
(baseline=110.0±8.3 vs. 132.0±14.3mmHg; p<0.05). Finally, renal Mφ-CD11c
+
-F4/80
+
purified from HTN animals and re-stimulated
in vitro
with AngII did not show changes in the mRNA levels evaluated (p>0.05).

Conclusions:
The AngII-HTN promotes a differentiated infiltration of DCs-CD11c
+
F4/80
-
and Mφ-CD11c
+
F4/80
+
in renal medulla. However, only renal DCs, and not renal Mφ, acquire the ability to transfer HTN, suggesting that renal CD11c
+
cell subpopulations may have a differential role in AngII-HTN.Supported by Fondecyt-ANID #1201251 and #3201016
Abstract 10266: T-Wave Features Predict Functional Worsening in Children With Pulmonary Arterial Hypertension: Machine Learning Insights From Standard ECG
Authors: Schafer Michal , Brateng Caitlin , Frank Benjamin , Hunter Kendall , Collins Kathryn , Stone Matthew , Mitchell Max B , Ivy Dunbar D , von Alvensleben Johannes
Published: June 2023

Introduction:
Various T-wave characteristics have been shown to be predictive of ventricular diastolic dysfunction and sudden cardiac death in adults. However, specific T-wave morphologies and their predictive potential in pediatric patients is unknown.

Hypothesis:
Machine learning derived T-wave characteristics will be different between children with pulmonary arterial hypertension (PAH) and healthy controls. Furthermore, T-wave characteristics will be predictive of clinical functional worsening in PAH patients.

Methods:
Principal component analysis (PCA) was applied to ECGs collected for children with PAH (n=155) at the time of diagnostic catheterization and matched healthy controls (n=47) to describe basic T-wave characteristics. Patients (<18 y/o) with PAH were defined as a mean pulmonary pressure >25 mmHg in the absence of obstructive left heart disease. Interpreted T-wave features were then compared between PAH and control groups. Identified T-wave measurements underwent survival analysis using standardized PAH functional class worsening as a clinical endpoint.

Results:
Identified T-wave principal components were 1) T-wave height and 2) early or late incidence of T-wave peak (FIGURE- 1A). The second principal component was associated with PAH diagnostic specificity (94%). Time from T-wave peak to T-wave end (TpTe) as measured in leads V4 to V6 was significantly higher in children with PAH (all P < 0.001) (FIGURE - 1B). V4 derived TpTe value > 132 ms and V5 derived TpTe value > 135 ms were associated with the higher probability of clinical functional worsening (P = 0.018 and P = 0.002, respectively) (FIGURE - 1C).

Conclusions:
T-wave features derived from standard ECG are 1) different between children with PAH and their healthy peers and 2) predictive of clinical functional worsening.
Abstract 10282: Early Anticoagulation Improves Post-Thrombotic Syndrome Outcomes and Experimental Restoration of Blood Flow in DVT Subjects
Authors: Li Wenzhu , Wang Dawei , Lee Hang , Li Guoping , Das Saumya , Weinberg Ido , Rosovsky Rachel , Reed Guy L , Libby Peter , Tawakol Ahmed A , Henke Peter , Jaffer Farouc A
Published: June 2023

Introduction:
Despite anticoagulation (AC), up to 50% of proximal deep vein thrombosis (DVT) patients will develop the post-thrombotic syndrome (PTS). In a substudy of the ATTRACT DVT trial, catheter-directedthrombectomy/thrombolysis (CDT) in addition to AC improved PTS outcomes for patients presenting at an intermediate day (D) 4-8 symptom-onset-to-randomization (SOR) timeframe, but not at an early D0-3 or late D9+ SOR timeframe. Mechanisms underlying the role of early AC and CDT are unknown, particularly iliofemoral DVT (IFDVT) patients that preferentially benefit from CDT.

Methods:
First, we assessed the temporal impact of AC on Villalta and VEINES-QoL PTS scores in a post-hoc analysis of the IFDVT ATTRACT patients (N=391). Mean scores were estimated by a piecewise linear-regression growth-curve model. Next, to mechanistically explore the effects of AC on PTS measures, C57/BL6 mice (N=76) underwent inferior vena cava (IVC) ligation to produce stasis DVT. Mice then underwent true or sham de-ligation at D2 to spur restoration of blood flow (RBF). Last, enoxaparin AC was initiated at D2 and given daily until D8, at either 0, 10, or 30 mg/kg/d SQ. D4 RBF rates in the IVC, and D8 thrombus burden were assessed.

Results:
In IFDVT ATTRACT patients, CDT+AC improved PTS scores in the intermediate D4-8 SOR timeframe (p<0.001 vs. AC alone). However, in the early D0-3 SOR timeframe, CDT+AC did not improve PTS scores (p>0.05 vs. AC alone). In the AC alone groups, early AC D0-3 significantly improved PTS scores over delayed AC (p<0.05). In sham de-ligated mice with IVC DVT, D2 enoxaparin improved D4 RBF rates (sham, 11.1%; low-dose, 33.3%; high-dose, 40.0%). D2 enoxaparin also significantly reduced D8 thrombus weight (p<0.05, both doses vs. saline). However, in true de-ligation mice, D2 enoxaparin only mildly increased D4 RBF rates (sham, 50%; low-dose, 61.5%; high-dose, 60%), and did not decrease D8 thrombus weight (p>0.05).

Conclusions:
In ATTRACT patients presenting with IFDVT at an early D0-3 SOR timeframe, PTS outcomes were improved by AC but not further improved by CDT. Experimentally, early D2 AC initiation can improve RBF rates and DVT resolution. These findings suggest that achieving early RBF may reduce the risk of PTS.
Abstract 10285: Prognostic Value of Provocative Spasm Test in Patients With Myocardial Infarction With and Without Obstructive Coronary Arteries
Authors: Ozawa Takaya , Goto Kenji , Miura Katsuya , Kimura Tomonari , Kobayashi Kazunari , Kikuta Yuetsu , sato katsumasa , Taniguchi Masahiro , Hiramatsu Shigeki , TAKEBAYASHI HIDEO , Haruta Seiichi
Published: June 2023

Introduction
: Coronary spasm potentially contributes to the pathogenesis of acute myocardial infarction (MI) with obstructive coronary artery disease (MICAD) and particularly warrants close consideration in MI with non-obstructive coronary arteries (MINOCA). However, there are limited data concerning the impact of coronary spasm in acute myocardial infarction (AMI). We aimed to assess the prognostic impact of provocative coronary spasm in both MICAD and MINOCA.

Methods:
Of 1,101 AMI patients admitted to our hospital from January 2012 to December 2019, 267 AMI patients (MICAD: n=198, MINOCA: n=69) who underwent emergency CAG and invasive provocative spasm test were assessed. The primary endpoint was a composite of major adverse cardiac events (MACE), defined as cardiovascular death, acute coronary syndrome, or revascularization. The median follow-up duration was 48 months.

Results:
Provocative test was positive in 143 (72.2%) of MICAD group and 33 (47.8%) of MINOCA group. In MICAD group, spasm-positive patients had a significantly higher occurrence of both MACE [27 (18.9%) vs. 4 (7.3%); p=0.0413] and Revascularization [25 (17.5%) vs. 3 (5.5%); p=0.0296] compared to spasm-negative patients. In MINOCA group, MACE occurred only in patients with spasm-positive [4 (12.1%) vs. 0 (0%); p=0.0473]. Among the 4 groups based on the type of MI (MICAD or MINOCA) and the presence of provoked coronary spasm, there was a significant difference in the MACE-free survival rate, with the lowest rate observed for MICAD patients with spasm-positive (log rank P=0.0111). In a Multivariable analysis, provoked coronary spasm was significantly associated with MACE in MICAD group (hazard ratio, 3.37;95% CI, 1.20-12.10; P=0.0189).

Conclusions:
Provocative spasm test could provide prognostic stratification for AMI patients.
Abstract 10291: Elevated C-Reactive Protein Level Amplifies the Association of Lipoprotein(a) With Cardiovascular Risk and Risk Reduction With Alirocumab After Acute Coronary Syndrome
Authors: Schwartz Gregory G , Szarek Michael , Bhatt Deepak , Bittner Vera A , Diaz Rafael , Garon Genevive , Goodman Shaun G , Harrington Robert A , Jukema J Wouter W , Manvelian Garen , Pordy Robert , White Harvey D , Zeiher Andreas M , Steg Philippe G
Published: June 2023

Background:
In the ODYSSEY OUTCOMES trial (NCT01663402) the PCSK9 inhibitor alirocumab [ALI] reduced the risk of cardiovascular events [CVE] after acute coronary syndrome [ACS] in patients [pts] with elevated atherogenic lipoproteins despite optimized statin treatment, an effect modified by baseline levels of lipoprotein [Lp](a). Levels of the inflammatory biomarker high-sensitivity C-reactive protein [hsCRP] are associated with risk after ACS. In this post hoc analysis, we determined whether Lp(a)-associated risk of CVE after ACS and reduction in that risk with ALI are modified by concurrent hsCRP levels.

Methods:
18,924 pts were randomized to ALI or placebo [PBO] 1-12 months after ACS and followed for median 2.8 years. Baseline Lp(a) and hsCRP were available in 18,290 pts. CVE [CV death, non-fatal MI, stroke, unstable angina or heart failure hospitalization, ischemia-driven coronary revascularization, peripheral artery events, and venous thromboembolism] were evaluated by baseline quartile of Lp(a) and by hsCRP dichotomized at 0.2 mg/dL.

Results:
Median (Q1-Q3) baseline Lp(a) was 21.3 (6.7-59.6) mg/dL. In 10,323 pts with baseline hsCRP<0.2 mg/dL (
Fig top
) risk of CVE in the PBO group increased modestly in Lp(a) Q4 (P
trend
=0.0592). Overall treatment hazard ratio [HR] was 0.91 without significant trend across Lp(a) quartiles. In 7967 pts with baseline hsCRP≥0.2 mg/dL (
Fig bottom
) risk of CVE in the PBO group was elevated and increased across Lp(a) quartiles (P
trend
<0.0001). Overall treatment HR was 0.82 and decreased across Lp(a) quartiles (P
trend
=0.0003).

Conclusion:
Elevated hsCRP amplifies the relationship of Lp(a) with risk of CVE after ACS and the reduction in that risk with alirocumab.
Funding:
Sanofi, Regeneron Pharmaceuticals
Abstract 10309: Susceptibility-Weighted Imaging is Not Inferior to CT in Detecting Intracranial Vertebral Artery Calcification
Authors: Liu Hon-Man
Published: June 2023

Susceptibility-Weighted Imaging is not inferior to CT in detecting intracranial vertebral artery calcification

Hon-Man Liu. Department of Medical Imaging, Fu-Jen Catholic University Hospital, Fu-Jen Catholic University, New Taipei City, Taiwan

Introduction:
Microcalcification is vulnerable and ready to rupture, and macrocalcification is more stable. CT is more sensitive to detect calcification than conventional MR. We demonstrated that the advance MR technique, susceptibility-weighted imaging (SWI), is not inferior to CT in detecting calcification of intracranial vertebral artery.

Hypothesis:
Susceptibility-weighted imaging can detect paramagnetic blood clots and diamagnetic calcification. Materials and methods: We reviewed the patients’ brain SWI imaging between January 2021 to March 2022 in our institute. The inclusion criteria were patients had SWI and brain CT done within 3 months. The exclusion criteria were poor imaging quality, insufficient study, and incomplete study. We defined that vessel wall calcification as void signal on SWI and hyper-attenuation (> or =100 HU) on CT. We compared the incidence and location of the calcification shown on CT and the void signal on SWI in the intracranial vertebral artery wall.

Results:
A total of 817 patients is eligible for this study. They were aged between 25 years to 90 years old and 393 were females. A 3.0T MR scanner was used in 486 patients, and 1.5T in 331. On CT, intracranial vertebral artery calcification was shown in 613 vertebral arteries. Susceptibility-weighted imaging could depict 98.5% (n=604) void signal at the corresponding intracranial vertebral artery segment shown on CT. Void signal on SWI is conspicuous in 12 foci that not shown as hyper-attenuation on CT.

Conclusion:
Susceptibility-weighted imaging is not inferior to CT in detecting intracranial vertebral artery calcification. SWI can play a role in the research about intracranial atherosclerosis in the future.
Abstract 10321: Safety of Catheter Ablation Therapy for Atrial Fibrillation in Cardiac Amyloidosis
Authors: Alhassan Hassan A , Akunor Harriet , Kainat Aleesha , Donohue Joseph , Baumgartner Scott , Saba Samir , Jain Sandeep , Soman Prem
Published: June 2023

Introduction:
Despite a high burden of atrial fibrillation (AF) in cardiac amyloidosis (CA), the safety of catheter ablation therapy (CAT) in CA is not well established. We sought to examine short-term safety outcomes following CAT for AF in patients with CA compared to matched patients with dilated cardiomyopathy (DCM).

Methods:
Using data from National Inpatient Sample (NIS), we identified all hospitalizations for AF CAT from the fourth quarter of 2015 through 2019. We matched CA to DCM admissions in a 1:5 ratio using propensity scores based on sociodemographic, clinical comorbidities, and hospital characteristics. We compared in-hospital outcomes including mortality, procedural complications, discharge disposition, total charges, and length-of-stay

Results:
Overall, 1,395 unweighted hospitalizations (representing 6,750 national hospitalizations) for AF CAT were included in analysis, out of which 45 (3.2%) were admissions for CA. Compared to DCM, CA patients were older (72.9years vs 65.1years), had a higher burden of prior stroke (20.0% vs 8.6%) and chronic kidney disease (53.3% vs 33.6%), and were less likely to have a prior ICDs (4.4% vs 23.0%). We matched 42 amyloid hospitalizations to 210 DCM hospitalizations. After matching, there was no difference in rate of in-hospital mortality (0.24 vs 0.33%, p=0.77), home disposition (97.6% vs 96.2%, p=0.65), total procedural complications (14.3% vs 10.5%, p=0.60), length-of-stay (3.1 days vs 2.1 days, p = 0.23) and total hospital charges ($137,250 vs $133,910, p=0.24).

Conclusions:
In this contemporary study of CAT for AF in CA, short-term safety outcomes and complication rates were similar to a propensity-score-matched cohort of DCM. Further studies exploring long-term safety outcomes are needed.
Abstract 10334: Vital Exhaustion and Cardiac Biomarkers - The Atherosclerosis Risk in Communities Study
Authors: Deshotels Matthew R , Al Rifai Mahmoud , Agha Ali , Sun Caroline , Selvin Elizabeth , Windham B Gwen , Vaccarino Viola , Michos Erin D , Jneid Hani , Levine Glenn N , Virani Salim S , Ballantyne Christie M , NAMBI VIJAY
Published: June 2023

Introduction:
Vital exhaustion (VE), defined as excessive fatigue and demoralization due to chronic stress, is a risk factor for cardiovascular disease (CVD), but the mechanism is unclear. We examined the association of VE with biomarkers of cardiac injury, neurohormonal stress and inflammation in the Atherosclerosis Risk in Communities (ARIC) study.

Methods:
Symptoms of VE were measured at ARIC visit 2 (1990-92, n= 11,588, mean age 57) using the Maastricht Vital Exhaustion Questionnaire (MVEQ). We analyzed the association of VE with cardiac biomarkers [High-sensitivity troponin T (Hs-TnT), N-terminal pro brain natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (Hs-CRP)] levels in adults without known CVD. Symptoms of VE (MVEQ scores) were categorized into quartiles. Elevated biomarker levels were defined as Hs-TnT ≥ 13 ng/L, NT-proBNP ≥ 125 pg/mL, and hs-CRP ≥ 2 mg/L. Logistic regression models adjusted for demographics and comorbidities were used to test for associations. The associations of VE (MVEQ score ≥16), elevated biomarkers, or both with incident CVD events after 6-year follow up was assessed by Cox proportional hazard regression.

Results:
Compared with the lowest quartile of VE (MVEQ ≤ 4), the highest quartile of VE (MVEQ 16-42), in adjusted models, was associated with elevated Hs-TnT, NT-proBNP, and hs-CRP [Odds Ratio (95% confidence interval) of 1.75 (1.34-2.29, p<0.01), 1.40 (1.19-1.64, p<0.01), and 1.14 (1.01-1.28, p<0.01), respectively]. The highest quartile of VE was associated with increased risk of CVD events. The risk was increased further in the setting of both significant VE (MVEQ ≥16) and elevated biomarkers (Table).

Conclusions:
Symptoms of VE are associated with elevated Hs-TnT, NT-proBNP, and Hs-CRP independent of traditional CVD risk factors. The presence of VE and elevated cardiac biomarkers is associated with high risk of incident CVD events in adults without CVD.
Abstract 10352: Characteristics of Survival in Older Patients With COVID-19: Insights From the American Heart Association COVID-19 Cardiovascular Disease Registry
Authors: Yeow Raymond Y , O'Leary Michael P , Reddy Akshay R , Kamdar Neil S , Hayek Salim S , De Lemos James A , Sutton Nadia R
Published: June 2023

Introduction:
The COVID-19 pandemic has accounted for over 6.2 million deaths worldwide, disproportionally impacting older patients. Understanding the characteristics of older patients who were hospitalized with COVID-19 and survived to hospital discharge could provide insights into key factors that confer resilience in the setting of critical illness in this population.

Methods:
We leveraged the American Heart Association COVID-19 Cardiovascular Disease (AHA COVID-19 CVD) Registry to identify determinants of in-hospital survival in older patients (age ≥80 years) hospitalized for COVID-19 through April 2021. Patients ≥80 years old who survived to discharge (excluding if discharged alive to hospice or against medical advice) were included. A hierarchical multivariable logistic regression model with random intercept for each hospital was used to identify characteristics associated with survival.

Results:
The study included 4,426 patients ≥80 years of age. The median age was 85 years (IQR 82-89). 53% were women. 73% were White, 14% were Black, and 3% were Asian. The mortality rate in this subcohort was 28%. Characteristics associated with survival included female sex (adjusted OR 1.3; CI 1.1-1.6; p< 0.001) and statin use prior to admission (adjusted OR 1.3; CI 1.1-1.6; p< 0.001). Conversely, characteristics negatively associated with survival included mechanical ventilation (adjusted OR 0.17; CI 0.13-0.22; p< 0.001), in-hospital shock (adjusted OR 0.33; CI 0.24-0.46; p< 0.001), and sustained ventricular tachycardia (adjusted OR 0.28; CI 0.13-0.60; p< 0.001).

Conclusions:
Female sex and statin use prior to admission were associated with improved survival in older patients hospitalized with COVID-19. The survival benefit associated with statin use and the increased susceptibility of older male patients to death from COVID-19 warrants further investigation.
Abstract 10362: Prognostic Value of Assessing Left Atrial Remodeling in Predicting Cardiac Events Following Transcatheter Aortic Valve Replacement
Authors: Kanzaki Hideaki , Irie Yuki , kakuta takashi , Okada Atsushi , Amaki Makoto , Takagi Kensuke , Kawamoto Naonori , Fujita Tomoyuki , Izumi Chisato
Published: June 2023

Introduction:
Left atrial (LA) volume indexed to body surface area (LAVi) is an established predictor of cardiovascular risk. The ratio of LAVi to mitral annular velocity during atrial contraction (LAVi/a') has emerged as a superior indicator to LAVi in assessing LA remodeling. However, the significance of calculating LAVi/a' in patients undergoing transcatheter aortic valve replacement (TAVR) has not been fully investigated.

Hypothesis:
The assessment of LA remodeling using LAVi/a' in patients with severe aortic stenosis (AS) provides crucial prognostic information after TAVR.

Methods and Results:
This study was composed of 486 patients with sinus rhythm (aged 83 ± 5 years; 175 men, 311 women) who underwent TAVR. Transthoracic echocardiography, including tissue Doppler, was performed before TAVR. Patients were divided into two groups according to the median LAVi/a'. The Kaplan-Meier method showed more adverse cardiac events (cardiac death and heart failure hospitalization) in the group with LAVi/a' above the median (log-rank test, P = 0.030). Multivariate Cox regression analysis adjusted for age and sex revealed that LAVi/a' was an independent prognostic parameter (hazard ratio, 1.058; P = 0.001).

Conclusions:
Patients with AS who have advanced LA remodeling are more likely to develop the adverse cardiac events even after successful TAVR. LAVi/a' is useful for predicting the cardiac events following TAVR and may be superior to LAVi.
Abstract 10368: Optimal Medical Therapy After Percutaneous Coronary Intervention in Very Elderly Patients With Coronary Artery Disease
Authors: Nakamura Takamitsu , Horikoshi Takeo , Kobayashi Tsuyoshi , Yoshizaki Toru , Uematsu Manabu , Watanabe Yousuke , Sato Akira
Published: June 2023

Introduction:
It is still unclear whether optimal medical therapy (OMT) after percutaneous coronary intervention (PCI) has beneficial effects on long-term clinical outcomes in patients aged ≥80 years with coronary artery disease (CAD).

Methods:
This study analyzed the time to the first major adverse clinical event, namely, death or nonfatal myocardial infarction (MI), for up to 3 years after PCI using multicenter registry data. Data for 1056 patients aged
>
80 years with CAD who were successfully treated with PCI were included in the analysis. OMT was defined as a combination of an antiplatelet drug, a statin, a beta-blocker, and an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker.

Results:
In total, 204 (19%) patients in this study received OMT and 852 (81%) received sub-OMT. During a median follow-up of 725 days, adverse clinical events occurred in 183 patients (death, n=177; nonfatal MI, n=6). Kaplan-Meier analysis showed that patients who received OMT had a lower probability of adverse clinical events than those who received sub-OMT (p<0.01, log-rank test). Propensity score matching yielded 202 patient-pairs treated with OMT or sub-OMT, in whom 64 adverse clinical events (death, n=59, nonfatal MI, n=5) occurred during follow-up. Kaplan-Meier analysis showed that patients who received OMT still had a lower probability of adverse clinical events than those who received sub-OMT (p=0.02, log-rank test). OMT remained significant in terms of reduction of the risk of adverse clinical events in a multivariate Cox proportional hazards model (hazard ratio 0.44; 95% confidence interval 0.26-0.75; p=0.003).

Conclusions:
OMT after PCI was associated with significantly fewer adverse clinical events, including all-cause death and nonfatal MI, in patients aged
≥
80 years with CAD. OMT might be safe and effective for these very elderly patients.
Abstract 10390: Using a Trial Modelling Framework to Emulate a Target Trial Evaluating Revascularisation Strategies in Patients With Heart Failure
Authors: Pathak Suraj , Lai Florence , Miksza Joanne , Petrie Mark , Murphy Gavin
Published: June 2023

Introduction:
We developed a novel trial modelling framework which utilises real world data to emulate a target trial and estimate key parameters to support trial planning. We applied this framework using the UK Hospital Episode Statistics (HES), which captures all admissions at NHS hospitals in England, and reported the findings of an emulated target trial evaluating revascularisation strategies in heart failure (HF) patients with coronary artery disease.

Methods:
Phenotyping algorithms derived from the target trial protocol were applied to HES, to identify HF patients who had coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA). Trial participants are often different from the target trial population due to voluntary basis of participation. The HES-derived cohort was matched on baseline features (age, gender, comorbidities) to an existing trial (STICH) which targeted the same high-risk population, so that the matched cohort mimics a likely trial population. Treatment effects were estimated using instrumental variable analysis (IVA) and meta-learning models to adjust for confounding.

Results:
A total of 13,519 HF patients undergoing revascularisation during April 2009 and March 2015 met the eligibility criteria. This HF patient cohort was matched with the STICH cohort, resulting in 2046 patients in the study cohort. The 5-year composite outcome of all-cause mortality or cardiovascular hospitalisation was observed in 51.1% of HF patients who had CABG and 70.0% in those who had PTCA. IVA showed that CABG was associated with a lower risk of the composite outcome (risk difference -16.2%, 95%CI: -20.6% to -11.8%). This was consistent with the treatment effects derived from other machine learning models. Our analyses also identified a trend in greater treatment effects being observed in the matched cohort than unmatched cohort. This suggests that a clinical trial may over-estimate treatment effects when compared to the actual treatment benefit observed in clinical practice.

Conclusions:
The framework provides a structured process to emulate a trial and anticipate findings of the trial. Our analyses showed that CABG is associated with a greater long-term benefit in HF patients requiring revascularisation.
Abstract 10400: The Characteristics and Outcomes of Heart Failure Associated With Methamphetamine Use
Authors: Forst Beani , Olagunju Abdulbaril , Bhattarai Bikash , Harwood Tyler , Fath Ayman , White Michael
Published: June 2023

Introduction:
Heart failure (HF) remains a significant cause of morbidity and mortality in the United States (US). Approximately 6.2 million adults in the United Status have HF and results in an estimated 13.4% of deaths annually. While the development of HF is linked to a variety of risk factors, the incidence and prevalence of methamphetamine-associated HF (HF-Meth) is rising secondary to the methamphetamine epidemic that is plaguing America. This study aims to compare the characteristics and outcomes of HF-Meth with other forms of HF.

Methods:
The discharge data of the National Inpatient Sample (NIS) from 2009 to 2014 were analyzed and records for HF hospitalization were identified using all ICD-9 codes for HF. These were further stratified based on meth use with the ICD-9 codes (304.40, 305.7, 969.72). We compared frequency of in-hospital mortality,incidence of cardiac arrhythmias, sudden cardiac death (SCD), rates of unemployment, and homelessness between patients with and without ICD-9 codes indicative of meth use. Percentage and chi-square-based P-values were reported.

Results:
Out of the 25,209,723 sampling weight-adjusted patients with ICD-9 codes indicative of HF, 58,359 (0.23%) had ICD codes indicative of Meth use. Relative to other patients with HF, HF-Meth experienced a lower in-hospital mortality rate (2.9 vs 5.0%, p <0.001), had a higher incidence of cardiac arrhythmias (7.1 vs 5.9%, p <0.001) and SCD (2.6 vs 1.8%, p <0.001), a higher rate of unemployment (0.49 vs 0.03%, p <0.001) and homelessness (6.1 vs 0.2%, p <0.001). In addition, HF-Meth was associated with a higher rate of alcohol abuse (21.1 vs 2.9%, p <0.001), cigarette smoking (73.8 vs 28.2%, p<0.001) and essential hypertension (43.8 vs 40.3%, p <0.001). Diabetes and hyperlipidemia were more prevalent in patients with other forms of HF (29.3 vs 43.44%, p <0.001 and 0.26 vs 0.45%, p <0.001 respectively).

Conclusions:
Patients with HF-Meth had a higher rate of cardiac arrhythmias, SCD, unemployment and homelessness. Additionally, they had a lower in-hospital mortality when compared with those not associated with meth use.
Abstract 10434: Very Late Stent Thrombosis Caused by Rupture of In-Stent Neoatherosclerosis 15-Years After Bare Nitinol Stent Implantation in Superficial Femoral Artery Visualized With Multimodality Imaging
Authors: Toyoshima Taku , Iida Osamu , Asai Mitsutoshi , masuda masaharu , Okamoto Shin , Ishihara Takayuki , Nanto Kiyonori , Tsujimura Takuya , Matsuda Yasuhiro , Hata Yosuke , Uematsu Hiroyuki , Higashino Naoko , Nakao Sho , Mano Toshiaki
Published: June 2023

A 77-year-old man complained of intractable rest pain in his left leg, which occurred one week before hospital admission. His past medical history included diabetes mellitus and history of smoking. He was prescribed cilostazol for treatment of peripheral vascular disease. He underwent endovascular therapy (EVT) 15-years earlier with a bare nitinol stent (BNS) implantation in his left superficial femoral artery (SFA), and no restenosis was detected by annual duplex ultrasound (DUS) follow-up until this session. DUS observed restenosis with 14.8 peak systolic velocity ratio, and initial angiography (
Panel A
, white arrow) revealed subtotal occlusion at the stented lesion. Intravascular angioscopy (
Panel C
) demonstrated disrupted cavity with red thrombus attached. Optical frequency domain imaging (OFDI) (
Panel D
) and intravascular ultrasound (IVUS) (
Panel E
) demonstrated fibrous cap disruption with a clear cavity formed inside the plaque (6 to 11 o’clock in Panel D and E), as well as thin sheet calcification. The other side (11 to 6 o’clock) shows a signal rich region with high attenuation that indicates fibroatheroma. The lesion was diagnosed as very late stent thrombosis (VLST) because multimodality images revealed rupture of in-stent neoatherosclerosis with red thrombus attached. After successful vessel preparation with a high-pressure 6mm balloon, 6 mm drug-coated balloons were used. The completion angiogram revealed an acceptable result with neither residual stenosis nor flow-limiting dissection (
Panel B
). Neoatherosclerosis has been reported as one of the major causes of VLST in the coronary arteries; however, it has rarely been reported in the peripheral arteries. This case illustrates valuable direct visualization with multimodality imaging of a case with VLST caused by rupture of in-stent neoatherosclerosis 15-years after BNS implantation, and the value of multimodality imaging for comprehensive evaluation to diagnose the mechanism of VLST in SFA.
Abstract 10442: Protective Effect of Inhibition of Sglt2 on Nanoplastics-Induced Premature Endothelial Senescence and Dysfunction
Authors: Dhakal Bikalpa , Shiwakoti Saugat , Ko Ju-Young , KANG KI-WOON , Schini-Kerth Valerie , Oak Min-Ho
Published: June 2023

Background:
Nanoplastics (NPs) are now widely acknowledged as a vital part of environmental pollution. However, the effects of NPs on the cardiovascular system are not well understood. We previously reported that NPs induce premature endothelial senescence and dysfunction via a redox-sensitive signaling pathway. Increasing evidence has shown that SGLT2 inhibitors (gliflozins) exhibit protective effects against the development of major cardiovascular diseases.

Objective:
This study aimed to investigate the role of SGLT2 on NPs-induced premature endothelial senescence and dysfunction, and, if so, to assess the effect of SGLT2 inhibition.

Methods:
Porcine coronary artery (PCA) rings and cultured endothelial cells (ECs) were exposed to NPs in the presence or absence of the SGLT2 inhibitor, Enavogliflozin (ENA), and the level of SGLTs expression, senescence-associated-beta galactosidase (SA-β-gal) activity, senescence markers, oxidative stress level, and vascular function were evaluated.

Results:
NPs were internalized in ECs in a time- and concentration-dependent manner. Exposure of PCAECs to NPs significantly up-regulated SGLT2 expression and increased SA-β-gal activity, one of the prominent senescence markers. ENA significantly reduced the NPs-induced increase of SA-β-gal activity in PCA and PCAECs. In addition, ENA prevented the NPs-induced up-regulation of senescence markers, p53, and p21 that promoted the inhibition of ECs proliferation. ENA prevented also the NPs-induced oxidative stress and up-regulation of NOX2 and p22phox in ECs. Exposure of coronary artery rings to NPs blunted endothelium-dependent relaxation and decreased the expression level of endothelial nitric oxide synthase level, and both of these effects were prevented by ENA.

Conclusion:
The present findings indicate that premature endothelial senescence and dysfunction induced by nanoplastics involve, at least in part, an upregulation of SGLT2, which is associated with increased levels of oxidative stress and the down-regulation of eNOS. They further raise the possibility that SGLT2 may be a potential target for preventing and/or treating environment pollution-associated cardiovascular diseases.
Abstract 10450: Interleukin-17A-Correlated Myocarditis in Patients With Psoriasis
Authors: Frustaci Andrea , Alfarano Maria , Richetta Antonio , Verardo Romina , Scura Felicita , Bagnato Giulia , Scialla Rossella , Chimenti Cristina
Published: June 2023

Background.
Psoriasis is a common immune-mediated disease of the skin with possible extension to joints, aorta and eye. Myocardial inflammation has been rarely suggested. However, its incidence and pathologic mechanism have not been elucidated so far.

Methods.
One hundred consecutive patients (62M/38F, mean age 55 ± 13.7 years) with psoriasis were screened for cardiac involvement. Among them, five male patients (mean age 56 ± 9.5 years) showed a dilated cardiomyopathy (LVEF < 40%) with normal coronary arteries and valves, and underwent a left ventricular endomyocardial biopsy for evaluation of myocardial substrate. Endomyocardial samples were processed for histology and immunohistochemistry, including myocardial expression of Toll-Like Receptor 4 (TLR4) and interleukin-17A (IL-17A), which plays a major role in psoriasis pathogenesis. Real-time PCR for cardiotropic viruses and Western blot analysis for myocardial expression of IL-17A were also performed. As controls for IL-17A expression, myocardial samples from 10 male patients with inflammatory cardiomyopathy and no psoriasis were included. Patients’ sera were tested for anti-heart autoantibodies.

Results.
An active lymphocytic myocarditis was revealed in all 5 patients, characterized by absence of viral genomes at PCR, positive anti-heart autoantibodies, overexpression of TLR-4 and of IL-17A at both immunohistochemistry (Figure 1A vs 1B) and Western blot analysis (mean value 44 ± 6.7 vs 12 ± 61.9 in patients with no-psoriatic myocarditis and 4± 1.5 in normal controls; Figure 1C).

Conclusion.
Interleukin-17A-related myocarditis can occur in up-to 5% of patients with psoriasis. It manifests as a progressive dilated cardiomyopathy that can potentially benefit from immunosuppression or monoclonal antibodies as the skin disease.
Abstract 10487: In vivo Efficacy of HS135, a Novel Activin and GDF Trap for the Treatment of Pulmonary Hypertension (PH) and Metabolic Syndrome (MetS)
Authors: Schang Gauthier , Poujol de Molliens Mathilde , Denis Jean-Francois , Chauvet Cristina , Brule Emilie , Schoelermann Julia , Tremblay Gilles , O'Connor-McCourt Maureen
Published: June 2023

Introduction:
PH is a disorder characterized by remodeling of the pulmonary vasculature which causes increased pulmonary vascular resistance and ultimately right ventricular (RV) failure leading to death. MetS is a recognized risk factor for PH, particularly in patients suffering from PH associated with left-sided heart failure (WHO Group 2 PH) for which there are no approved therapies.

Activins and growth differentiation factors (GDFs) are implicated in both PH pathology as well as body composition and metabolism by genetic disease association, preclinical, translational, and clinical evidence.

HS135 is a rationally designed first-in-class activin-receptor (ActR)-based fusion protein that addresses both vascular remodeling and MetS in PH without affecting hematological parameters; hematological effects limit the dosing of other ActR-based agents.

Methods:
HS135’s ability to counteract vascular remodeling and heart failure in PH was assessed using a rat monocrotaline (MCT) model: a single dose of 60 mg/kg MCT was administered on Day 0 followed by 4 weeks of twice weekly treatment with either HS135 (1, 4, or 16 mg/kg) or vehicle. PH efficacy was assessed at end of study by echocardiography and histological readouts. HS135’s ability to improve body composition and metabolism was assessed in wild type mice by administering HS135 (1, 3, 10, 20, or 50 mg/kg) or vehicle twice weekly for 3 weeks. The effect of HS135 on hematological parameters was assessed by whole blood cell count in non-human primates (NHPs) 2 weeks following a single administration of HS135 at 3 or 30 mg/kg.

Results:
HS135 at 3 or 30 mg/kg did not lead to changes in hematological parameters in NHPs. Compared to vehicle, HS135 was effective at counteracting the MCT-induced PH phenotype in rats as evidenced by significant reductions in Fulton index and improved echocardiography parameters. In wild type mice, HS135 led to significant improvements in body composition.

Conclusions:
Contrary to other ActR-based therapies, HS135 did not lead to increases in hematocrit which would limit its dosing. HS135 was efficacious at treating PH while simultaneously improving body composition in preclinical models. Clinical trials with HS135 are expected to commence within 2023.
Abstract 10515: Mechanical Dyssynchrony in Patients With a Fontan Circulation and Its Relationship to Outcomes
Authors: Gearhart Addison , Bassi Sunakshi , Dionne Audrey , Gold Maxwell P , Harrild David M , Rathod Rahul H , Ghelani Sunil J
Published: June 2023

Introduction:
The prevalence and significance of mechanical dyssynchrony is not well known in the Fontan population.

Methods:
Single-center, retrospective analysis of CMRs in Fontan patients compared to healthy controls. Feature tracking was performed on all slices of a short-axis cine stack and dyssynchrony index (DI) was defined as the standard deviation of time-to-peak circumferential strain for all segments. A composite outcome was defined as death, heart transplant listing, or new ventricular arrhythmias.

Results:
A total of 512 cases (17±9 y) and 42 controls (16±9 y) were included. Figure 1 depicts differences in EDV

i

, EF, DI, and QRS duration between the cohorts. DI correlated with EDV

i

(r=0.35; p<0.01), EF (r=-0.29; p<0.01), and QRS duration (r=0.29; p<0.01). At a median follow-up of 4.2 yrs, 10% had death or transplant listing and 4% had ventricular arrhythmias. RV dominance, EDV

i

, EF, DI, and QRS interval were associated with increased risk of the composite outcome (Table 1). Figure 2 demonstrates a significantly higher probability of the composite outcome in those with EDV

i

>120 ml/m
2
and DI>70 ms.

Conclusion:
Fontan patients have more mechanical dyssynchrony and longer QRS duration compared to controls. These abnormalities are more pronounced in RV or mixed ventricular morphology and are associated with a higher risk of ventricular arrhythmias, transplant listing, or death.