bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16752: Aortic Pulsatility, and Not Mean Arterial Pressure, is an Independent Determinant of Left Main Coronary Artery Disease
Authors: Mahmud Azra , Balghith Mohammad , Ayoub Kamal , Khan Fayaz , AlChighouri Samir , Al Mutairi Fawaz , Al Ghamdi Ali
Published: April 2024

Introduction:
Left main coronary artery(LMCA) disease is prognostically the most important lesion in the coronary tree. LMCA differs from the other coronaries in having high elastin content. As aortic blood pressure (BP) directly affects the heart and emerged as independent predictor of major cardiovascular events, there is heightened interest in exploring its relationship with coronary artery disease (CAD). Aortic pulsatility (AP) measurement eliminates the effect of cardiac output and vascular resistance and is shown to be an independent predictor of cardiovascular events in CAD.

Hypothesis:
As the left main is an elastic vessel, we hypothesized that pulsatile stress may be an independent determinant of disease in this artery.

Methods:
This was a prospective cohort study in patients undergoing coronary angiography for suspected CAD between the years 2011 and 2016(n=4633, 25% female) at King Abdul Aziz Cardiac Center, Riyadh, Saudi Arabia. We excluded patients with acute myocardial infarction, cardiogenic shock and significant valvular heart disease. Aortic systolic and diastolic BP were measured in the ascending aorta. MAP was obtained by direct integration of the BP curve. PP was calculated as the difference between systolic and diastolic BP. AP was calculated as PP divided by MAP. CAD was defined as > 50% stenosis in LMCA and the 3 major coronaries (left anterior descending, circumflex and right coronary artery). The AP in patients with LMCA disease was compared to those with non-obstructive, 1, 2 and 3-vd as well with LMCA and 3-vd.

Results:
Six percent of the study population had LMCA disease (mean age 60±11 years, 25% female). LMCA disease was associated with higher PP (69±22 vs. 58±18, p<0.0001) despite similar MAP (94±16 vs. 94.5±14, p=0.92) compared with non-LMCA disease. AP was significantly higher (0.72±0.30) in LMCA disease compared with; 3-vd( 0.63±0.32); 2-vd(0.61±0.28), 1-vd(0.58±0.31) and non-obstructive CAD (0.52±0.26) (p<0.0001). In a stepwise regression model, AP was an independent predictor of LMCA disease( R
2
=0.68,P<0.0001) when adjusted for potential confounders, including MAP, age and gender.

Conclusions:
We conclude that LMCA disease is independently associated with high aortic pulsatility compared with disease of other coronary vessels,including 3-vd. Considering aortic pulsatile stress to be an independent cardiovascular prognosticator, stiffness of the LMCA may play an important role in plaque formation, hitherto ignored. More research is warranted to test our proof-of-concept study, including outcome.
Abstract 16764: Aging-Related Myofibroblastic Transition in Aortic Valve Interstitial Cells Elevates Valvular Osteogenic Response to Oxidized Low Density Lipoprotein
Authors: Zeng Qingchun , Yao Qingzhou , Ao Lihua , Xu Dingli , Furllerton David , Meng Xianzhong
Published: April 2024

Calcific aortic valve disease (CAVD) is the most prevalent heart valve disorder in the elderly. The pathobiology of this disease involves chronic inflammation, fibrosis and calcification. However, the molecular mechanism underlying CAVD progression remains obscure. Diseased aortic valves display higher levels of oxidized low-density lipoprotein (oxLDL), and oxLDL has the potential to interact with Toll-like receptors (TLRs) in aortic valve interstitial cells (AVICs) to elevate cellular osteogenic activity. We tested the
hypotheses
that aging-related myofibroblastic transition in AVICs elevates valvular osteogenic response to oxLDL.

Methods and Results:
AVICs from normal valves of young (20-30 years old) and older (60-70 years old) people were treated with oxLDL (40 μg/ml) for 3-14 days in vitro. OxLDL had a greater effect on the up-regulation of bone morphogenetic protein-2 (BMP-2) and alkaline phosphatase (ALP), as well as on the induction of calcium deposition, in AVICs from older donors. The exaggerated pro-osteogenic effect of oxLDL in AVICs of older donors was associated with over-expression of myofibroblastic biomarker α-smooth muscle actin (α-SMA), and knockdown of α-SMA with lentiviral shRNA markedly attenuated the osteogenic response. Further, oxLDL induced greater activation of ERK1/2 and NF-κB in AVICs of older donors. Inhibition of ERK1/2 or NF-κB greatly diminished the effect of oxLDL on BMP-2 and ALP expression in AVICs from both young and older donors.

Conclusions:
The results of this study show that oxLDL exerts a greater impact on AVICs of older subjects to elevate the pro-osteogenic activity through activation of the ERK1/2 and NF-κB pathways. AVIC myofibroblastic transition associated with aging is responsible, at least in part, for the elevated osteogenic response to oxLDL. These findings reveal a novel mechanism underlying CAVD pathogenesis and indicate that suppression of AVIC myofibroblastic transition in the elderly patients may have the therapeutic potential for suppression of CAVD progression.
Abstract 16772: Gender Differences in the Presentation and Prognosis of Patients With Danon Disease
Authors: Brambatti Michela , Maolo Alessandro , Koshi Elliott , Taylor Matthew , Adler Eric
Published: April 2024

Background:
Danon Disease (DD) is a rare X-linked disorder with high morbidity and mortality. Clinical features include skeletal myopathy, hypertrophic cardiomyopathy (HCM), and neurologic symptoms. The first cases were described in 1981; however, gender differences are still poorly understood.

Methods:
From 773 manuscripts published from 2000-2017 in MEDLINE and EMBASE, we identified 180 cases. We included in the principal analysis 146 patients diagnosed with a genetic test (if index case) or muscle biopsy (if a relative of the index case).

Results:
Symptoms first occurred in males significantly earlier than females (median age 9 years vs. 23 p<0.001). Cardiomyopathy occurred in 91% of patients, the majority of whom had HCM. Thirty-seven (25.3%) patients received automated cardiac defibrillators, as primary prevention in 64.9% of cases. Males with hypertrophy were twice as likely to develop advanced heart failure at a median age of 21 years. Conversely, dilated cardiomyopathy (DCM) was 4 times more prevalent in females (n=12, 75%) compared to males (n=3, 19%). Intellectual disability was significantly more frequent in males (53.9% males vs. 9% females with a median age of onset of 6 and 19, respectively, p=0.829). Abnormalities in the laboratory tests, such as AST, ALT or CK were described in 62.5 % of the population (83.3% of males and 15.6% female). Muscle myopathy was described in 64 (49%) cases - 57 (63.3%) males and 7 (12.7%) females- at a median age of 13 years and 19, respectively (p=0.826). Overall, 51 patients (34.9 %) died or required a left ventricular assist device (LVAD) or heart transplant (HTx). Median age at the time of death/HTx/LVAD was 26 years and 52 years in males and females, respectively (p <0.001 by the log-rank test) (fig 1). Although not statistically significant, males were more likely to experience temporary complications after HTx compared to females (25% vs. 0%, p=0.136).

Conclusions:
Despite being an X linked disease, females with Danon have significant morbidity and a shortened lifespan. DCM is more prevalent in females, while HCM and post-Htx complications were more prevalent in males. Both genders had a prolonged survival as compared to prior studies, possibly reflecting increased awareness and earlier diagnosis.
Abstract 16780: Prevalence, Treatment, and Outcomes Among Asian Subgroups With Coronary Artery Disease
Authors: Manjunath Lakshman , Chung Sukyung , Li Jiang , Palaniappan Latha , Yong Celina M
Published: April 2024

Introduction:
Asians are the most rapidly growing minority population in the United States, yet coronary artery disease (CAD) treatment and outcomes among Asian subgroups remain poorly understood.

Methods:
We analyzed 772,882 patients receiving care from the Palo Alto Medical Foundation from 2006-2015 to determine whether CAD treatment and outcomes differ by race, including Asian subgroups, with adjustment for age, gender, household income and comorbidities.

Results:
Among the cohort, 219,150 patients were Asian (38.5% Asian Indian, 28.4% Chinese, 9.6% Filipino, 4.2% Japanese, 3.2% Korean, 2.1% Vietnamese, and 14.1% “Other Asian”). Among those who received angiogram, prevalence of CAD was highest among Asian Indian (81.3%), Chinese (83.3%), and Filipinos (82.4%). Compared to Non-Hispanic Whites (NHW), Chinese were more likely to receive a stent (50.9% vs 60.8%, adj OR 1.4 [95% CI 1.0 - 1.9], p = 0.005), while Filipinos were more likely to undergo CABG (6.9% vs 20.5%, adjusted OR 2.7 [CI 1.9 - 4.0], p <0.0001). After stenting, Chinese, Filipinos, and Japanese were more likely to be prescribed clopidogrel compared to NHW (86.2%, 83.0%, and 91.4% vs 74.5%, adj ORs 1.8 [CI 1.1 - 3.0], 1.9 [CI 1.0 - 3.4], and 4.4 [CI 1.0 - 18.7] respectively, p <0.0001) but there were no significant differences in prasugrel prescription by race. There were no significant differences by race in post-angiogram 1-year mortality, stroke, transient ischemic attack, or bleeding. However, Chinese and Asian Indians were more likely to be diagnosed with a myocardial infarction within 1 year following coronary angiography compared to NHW (15.6% and 17.4% vs 11.2%, adj ORs 1.5 [CI 1.0 - 2.2] and 1.7 [CI 1.2 - 2.3] respectively, p <0.0001, see Figure).

Conclusions:
Disaggregation reveals significant diversity in CAD treatments and outcomes by Asian subgroup, highlighting potential opportunities to meet the needs of growing Asian populations in the United States.
Abstract 16784: Participation in Thrill-Seeking Activities for Hypertrophic Cardiomyopathy Patients
Authors: Papoutsidakis Nikolaos , Salberg Lisa , Ingles Jodie , Semsarian Christopher , Mannello Meghan , Olivotto Iacopo , Maurizi Niccolo , Waldman Cynthia , Heitner Stephen , Jacoby Daniel
Published: April 2024

Introduction:
Hypertrophic Cardiomyopathy (HCM) is the most common inherited cardiomyopathy and an important cause of sudden cardiac death in young. Previous work suggests that adrenergic stimulation during thrill-seeking activities may be dangerous for cardiac patients. Based on this and the Bethesda guidelines many physicians advise against participation.

Hypothesis:
We hypothesized that many patients would continue to participate in these activities and we sought to examine their characteristics and outcomes.

Methods:
Patient advocacy organizations (HCMA), social media outlets and collaborating centers invited HCM patients to complete an anonymous online survey, providing information about participation in thrill-seeking activities (Rollercoaster riding, Jet skiing, Rafting, Bungee jumping, Rappelling, Paragliding, Kayaking/canoeing, Motor racing, Snowboarding, BASE jumping, Skydiving) and associated symptoms.

Results:
Out of 633 responders, (age: 51.3+-14.4 years, 351 F, 272 M), 556 had engaged in thrill-seeking activity, with 331 continuing after HCM diagnosis. The cohort was high-risk for arrhythmias (24.4% daily symptoms, 45% post ICD, 13.8% post ICD shock, 31.4% history VT). Over a total of 7994 participations, 187 subjects (33.6%) experienced minor events consisting of nausea, dizziness, chest pain or palpitations. Nine subjects (0.02%) reported significant events during or within 60 min of participation [8 syncopal events (4 during rollercoaster riding, 4 during other activities), 1 ICD shock (during skiing)] (Figure 1).

Conclusions:
This is the first study to assess the safety of thrill-seeking activities for HCM patients. A significant number of patients participated in thrill-seeking activities even after HCM diagnosis. These activities are often associated with mild symptoms but rarely lead to significant events (syncope, ICD shock) in this high-risk population of HCM patients.
Abstract 16787: Aneurysmal Dilatation of the Main Pulmonary Artery in Patients With Isolated Pulmonary Stenosis: An Intrinsic Arteriopathy or a Flow-Related Sequela?
Authors: Ruijsink Bram , Miglianti Michela , Duong Phuoc , Frigiola Alessandra
Published: April 2024

Introduction:
In patients with isolated pulmonary stenosis (iPS), dilatation of the MPA has been reported, sometimes developing into large aneurysms (giantPA). The incidence, aetiology, natural history, and its treatment.

Methods:
We identified all patients with iPS that attended our tertiary cardiac centre (one of the largest in the UK) between 2003 and 2018 and reviewed clinical notes, echocardiography and MRI data. We evaluated the incidence of MPA dilatation in patients with iPS and its relation to age and pulmonary valve (PV) function.

Results:
197 patients (107 children, 90 adults) with iPS were identified. 122 (62%) underwent balloon dilatation of PV for severe stenosis (median age 0.65 IQR 0.08-5.18 years), 30 (15%) underwent PV repair or replacement (median age of 2.06 IQR 0.9-5.2 years) and 45 (22.8%) did not require any procedure. In patients that did not require a procedure, mean peak velocity on echocardiography was 2.55±0.65 m/sec. In patients that required an intervention, the MPA was normal to mildly dilated in most patients (mean z-score +1.2±2.6). In patients who did not undergo any procedure, the size of the MPA was only weakly correlated with age (R
2
.10
p
<.01) and severity of PV stenosis (
p
<.22). 12 patients (6% of total population) had giantPA (z-score > 4 in children, diameter > 50 mm in adults). Mean size of the largest diameter of the MPA was +5.8±1.9 z-score in children and 59±5 mm in adults. Of these patient 58% had undergone a procedure (mean age 11±14 yrs). Of note, while in the paediatric cohort the MPA size was easily obtained using echocardiography, in only 30% of adult patients the MPA was well visualized and there was a significant error (25±27%) in the provided measurements compared to 3D imaging obtained with MRI. In 7 of 8 adults with giantPA , diagnosis was made only with MRI.

Conclusion:
In patients with iPS, the incidence of giantPA is not negligible (at least 6%). MPA dilatation does not seem to correlate with PV function thus suggesting an underlying arteriopathy rather than a flow-related aetiology. In adults, MPA size is unreliably assessed using echocardiography. 3D imaging is therefore indicated in adults patients with iPS even in the presence of mild PV dysfunction.

Total; word count : 1875 characters

Figure 1: No impact of stenosis severity on MPA size in patient who did not undergo PV repair or replacement

Figure 2: Aneurysmal dilatation of the MPA in a patient with isolated pulmonary stenosis (in this case mild stenosis).
Abstract 16794: Early Detection of Myocardial Fibrosis by Electrocardiographic Abnormalities in Sickle Cell Patients
Authors: Macias Enriquez Eduardo , Johnson Mark
Published: April 2024

Introduction:
Advances in screening and treatment of sickle cell disease (SCD) continue to increase life expectancy of this population. As a result, mortality from cardiopulmonary causes has become the most prevalent cause of death. While the specific etiology of cardiac death remains unclear, multiple studies have shown that diastolic dysfunction and prolonged QT are associated with early mortality in SCD. Recently, the physiopathology of a novel cardiomyopathy with both restrictive and hyperdynamic features was described in the SCD population. In addition, a high incidence of repolarization nonspecific abnormalities has been reported in SCD patients. Although these serve as surrogates for repolarization heterogeneity, because of difficulty in reproducibility and measurability they are rarely considered of clinical significance.

Hypothesis:
Repolarization abnormalities are the earliest manifestation of microvascular changes and fibrosis in the myocardium of SCD patients.

Methods:
We performed a retrospective electrocardiographic and echocardiographic analysis of 88 patients from our SCD clinic. We used commercially available QT guard plus (QTgp) software to analyze repolarization heterogeneity parameters, and performed echocardiographic measurements of previously validated diastolic markers. In addition, data from 77 individuals - matched demographically with our SCD population- with structurally normal hearts and with normal ECGs was analyzed with QTgp.

Results:
Our statistical analysis showed correlation between Left ventricular mass index (LVMI), and mitral E/a ratio with T wave morphology changes (T peak, T offset, t wave morphology dispersion, and QRST vector) (table 1). In addition we found that T wave morphology was significatively different between our healthy controls and our SCD population (table 2).

Conclusion:
T wave morphology changes could be used as an early marker of diastolic dysfunction and increased LVM in the SCD population.
Abstract 16815: GJA1-20k, a Truncated Isoform of Connexin 43, Nucleates
De Novo
Actin Clusters
Authors: Baum Rachel , Hong TingTing , Kleber Andre G , Shaw Robin M
Published: April 2024

Introduction:
Connexin 43 (Cx43) gap junctions allow rapid communication of signals between cardiomyocytes. Loss of Cx43 gap junction coupling contributes to arrhythmogenesis. GJA1-20k, a truncated internally translated isoform of the Cx43 gene
GJA1
, is necessary for full length Cx43 trafficking to intercalated discs for gap junction formation. GJA1-20k stabilizes actin filaments, necessary for the Cx43 delivery highway. The mechanism of GJA1-20k interaction with actin, while essential for gap junction formation, is still not known.

Methods:
Cell free individual actin dynamics were observed by TIRF microscopy. For real time imaging of actin nucleation and polymerization, glass bottom chamber slides were pre-incubated with 100nM N-ethylmaleimide myosin and loaded with Alexa Fluor 488-conjugated actin (Thermo Fisher) with GJA1-20k in ATP containing buffer. Actin binding assays were performed using a spin-down assay kit (Cytoskeleton, Inc.). Actin polymerization was studied by using pyrene labeled actin (Cytoskeleton, Inc.).

Results:
Cell free biochemical binding assays show that GJA1-20k binds to G-actin molecules, nucleating
de novo
actin clusters yet also surprisingly preventing G-actin polymerization. Pyrene actin assays further confirm that GJA1-20k alone does not promote polymerization. Cell free TIRF imaging also reveals that GJA1-20k promotes the formation of
de novo
G-actin clusters (Figure 1). Once a critical degree of nucleation is present however, polymerization occurs at a rate that promotes the formation of thicker actin fibers. Because GJA1-20k preferentially supports nucleation over polymerization, GJA1-20k introduces novel foci of new actin growth that, when a critical mass is present, rapidly overflows to polymerization.

Conclusions:
GJA1-20k nucleates
de novo
actin clusters, and thus is able to seed novel cytoskeleton growth patterns, dictating the direction of gap junction delivery.
Abstract 16822: Endothelial c-Myc Protects the Heart From Pro-Inflammatory Changes During Aging and Atherogenic Stress
Authors: Qi Yue , Pinto Mariana T , Florea Victoria , Lassance-Soares Roberta , Rodrigues Claudia O
Published: April 2024

Background:
Inflammation plays an important role in cardiac remodeling and occurs in response to risk factors such as aging and high-fat diet (HFD). We have recently reported that c-Myc knockdown in endothelial cells triggers a senescence-associated pro-inflammatory phenotype. We found that c-Myc expression declines in human coronary artery endothelial cells (HCAECs) during replicative senescence and aging. These findings suggest that threshold levels of c-Myc in endothelial cells are required to protect the heart. Here we investigated the impact of endothelial c-Myc in the heart during aging and exposure to HFD using a transgenic mouse model with endothelial-specific c-Myc overexpression.

Methods and Results:
Gene expression profiling and pathway analysis of young (2-month) and old (10-month) mice showed that endothelial c-Myc overexpression has a protective effect, increasing the expression of genes that prevent cardiac hypertrophy such as Rgs2, Braf and Ppargc1a and reducing inflammatory mediators such as S100a9 and Ptx3. We validated the expression of inflammatory markers IL-1β, Cxcl1 and TGF-β2 by qPCR and found that in aged group, their expression was downregulated in transgenic mice by 2.46 (p<0.002), 2.92 (p<0.001) and 1.85 (p<0.001) fold, respectively, relative to control mice. We further explored this novel protective role of c-Myc in the context of HFD using pre-designed Taqman stress array. Results showed significant downregulation of genes involved in oxidative stress (Noxo1, -1.72-fold, p<0.01), autophagy (Tfeb, -1.72-fold, p=0.03) and DNA repair (Bub1b, -1.37-fold, p=0.02) in transgenic mice under control diet. In response to HFD, most stress genes were downregulated in control mice while a specific group was upregulated in transgenic animals, including genes involved in autophagy (Tfeb, 1.39-fold, p=0.06) and antioxidant pathways (Txnrd2, 1.58-fold, p=0.03; Msra, 1.72-fold, p=0.04 and Msrb3, 1.47-fold, p=0.05).

Conclusion:
Our c-Myc overexpression mouse model exhibits a distinct gene expression pattern that is potentially cardiac protective in response to aging and HFD. Endothelial c-Myc may be essential to protect cardiac tissues under stress conditions.
Abstract 16825: Functional Analysis of Whole Exome Sequencing Candidate Genes for Left Ventricular Hypertrophy Demonstrate Changes in Cardiac Hypertrophic Signaling
Authors: Olson Benjamin , Aggarwal Praful , Irvin Marguerite , Srinivasasainagendra Vinodh , Zhi Degui , Zhi Degui , Gu Charles , de las Fuentes Lisa , Turner Amy , Matter Andrea , Tiwari Hemant , Nickerson Deborah A , Arnett Donna K , Broeckel Ulrich
Published: April 2024

As whole exome sequencing (WES) studies identify a large number of potential disease relevant genes and variants, a major challenge will be the subsequent functional analysis and interpretation. We performed WES in 1,382 African American subjects from NHLBI’s HyperGEN cohort to identify novel genes for Left ventricular (LV) hypertrophy.

Using criteria that combine significant prior linkage/association signals, expression QTL information, database annotation, and literature search, we prioritized the candidate genes to further scrutinize those with higher functional potentials. As a result, we selected four genes (
FATP6, PDE12, HAX1, TRAPPC11
) that had not been directly linked to LVH for experimental functional follow up using human iPSC-derived cardiomyocytes (hiPSC-CM). Each gene was knocked-down (KD) using siRNAs in triplicate followed by mRNA sequencing. Differential expression and pathway analyses were performed to evaluate influences of the candidate genes. The KDs of
FATP6
and
PDE12
, whose variants show significant association with increased LV internal diastolic-dimension, showed regulation changes in cardiac hypertrophy and β-adrenergic signaling pathways (p-value <0.05). In FATP6 KDs we observed 2,696 genes to have significant differential expression (adj. p-value ≤0.05). Furthermore,
FATP6
KDs also lead to the upregulation of cholesterol biosynthesis pathways (p-value 1.97E-4) that are important for caveolae formation and signal transduction. Additionally,
FATP6
KDs had a moderate increase in
FATP1
expression (p-value 0.0024) that has been reported to cause lipotoxicity and increase LV internal diastolic diameter in mice. In
PDE12
KDs we observed significant differential expression of 3,276 genes (adj. p-value ≤0.05) and saw significant decreases in Ca2+ channel expression (adj. p-value ≤0.05) that likely lead to decreases in Ca2+ handling.

In summary, our study demonstrates the hiPSC-CM based knockdown model as an effective approach to functionally test and characterize candidate genes identified through WES. Further development of the approach using hiPSC derived cells will offer a scalable platform for high-throughput, multi-omics analyses using genome-matched, disease-relevant tissue types.
Abstract 16826: Reversal of TSPO Upregulation in the Diabetic Heart by Chronic TSPO Gene Silencing Causes Metabolic Sink via an Increase in ROMK Expression
Authors: Ilkan Zeki , Strauss Benjamin , Akar Fadi G
Published: April 2024

Introduction:
The mitochondrial translocator protein (TSPO) is an integral component of a macromolecular complex that regulates cell death & survival pathways. Myocardial TSPO levels are markedly increased in diabetes.

Objectives:
We sought to investigate the electrophysiological effects of TSPO in diabetes using a cardiotropic TSPO gene silencing approach that avoids off-target effects of TSPO ligands.

Methods:
In a standard model of diabetes mellitus consisting of Zucker Obese rats, AAV9.shTSPO (5E11 gc/mL) was delivered by tail vein injection (N=5). Non-diabetic lean (N=4) and spontaneously hypertensive (N=16) rats served as treatment controls. Untreated diabetic (N=6) and non-diabetic (N=6) hearts were also studied. The TSPO ligand DZP (64μμ) was perfused in additional diabetic hearts to contrast its effects with those of chronic TSPO knockdown. Optical action potential (AP) mapping was performed 2 wks following gene transfer. Hearts were challenged with 12 min ischemia followed by reperfusion.

Results:
Myocardial TSPO knockdown by AAV9.shTSPO promoted metabolic sink in diabetic hearts. This manifested as rapid and spatially heterogeneous loss of AP amplitude and upstroke velocity in response to ischemia (Figure). Areas of early loss of excitability remained inexcitable upon reperfusion resulting in wide regions of conduction block that supported VT. These findings were specific to diabetes as AAV9.shTSPO did not alter the response of non-diabetic hearts to ischemia. Loss of excitability was not related to irreversible cell death by TUNEL staining. Analysis of the expression of ATP-sensitive channel subunits revealed marked upregulation of ROMK in response to TSPO knockdown exclusively in the diabetic heart. Unlike TSPO knockdown, DZP did not promote metabolic sink but rather prevented post-ischemic VT.

Conclusions:
Chronic gene silencing of TSPO promotes VT via a metabolic sink mechanism likely arising from compensatory upregulation of ROMK.
Abstract 16830: Late Removal of a pLVAD Increases Mortality
Authors: Chen Qi , Pollet Mark , Mehta Adwait , Dean Juliette , Parenti Jennifer , Rojas Francia , Xi Yutao , Cheng Jie , Mathuria Nilesh
Published: April 2024

Objective:
The impact of the timing of removal of a percutaneous left ventricular assist device (pLVAD) during VT ablation on outcomes is uncertain. We compare the outcomes of patients with early (≤ 24 hours) versus late (>24 hours) removal of pLVAD during VT ablation.

Methods:
We reviewed the data of 27 male patients who underwent VT ablation with pre-emptive pLVAD support between March 2013 to November 2017. There were 2 groups: (1) Early removal group: pLVAD was removed in ≤ 24 hours after VT ablation (n = 18), (2) Late removal group: pLVAD was removed > 24 hours (n = 9).

Results:
There was no significant difference of age (67.33 ± 12.67
vs.
60.67 ± 14.93 yrs, p = 0.236), Diabetes (both 33.3%), ICMP (56%
vs.
44%, p = 0.60), COPD (16.7%
vs.
11.1%, p = 0.71), VT storm (both 22.2%), procedure duration (391.5 ± 70.76
vs.
395.67 ± 126.32 min, p = 0.912) between the 2 groups. There was a trend towards longer VT duration during the procedure in Group 2 (28.00 ± 27.16
vs.
60.4 ± 25.1 min, p = 0.148). The LVEF in group 1 is significantly higher (28.09% ± 9.44%
vs.
20.00 ± 2.50%, p = 0.019). The 90-day mortality was higher in group 2 (11.1%
vs.
44.4%, p = 0.025).

Conclusions:
Late removal (>24 hours) of a pLVAD for VT ablation is associated with an increased 90-day mortality. Severely depressed LVEF and potentially prolonged time in VT may predict poorer outcomes despite pLVAD support.

Figure 1
Kaplan-Meier Survival Curve of the patients with structural heart disease undergoing catheter ablation of ventricular tachycardia under the support of percutaneous left ventricular assist device (pLVAD) (group 1: patient had pLVAD removed ≤ 24 hours after VT ablation; group 2: patient had pLVAD removed >24 hours after VT ablation)
Abstract 16833: Long-Term Outcomes and Complications of Anticoagulant Therapy for Bioprosthetic Valve Thrombosis in a Large Matched-Cohort Study
Authors: Petrescu Ioana , Ionescu Filip , Nkomo Vuyisile T , Connolly Heidi M , Pellikka Patricia A , Pislaru Cristina , Egbe Alexander C , Pislaru Sorin V
Published: April 2024

Introduction:
Bioprosthetic valve thrombosis (BPVT) is a well-recognized cause of prosthetic dysfunction. Anticoagulation restores prosthetic valve gradients, but long term outcomes and complications from therapy are unknown.

Objectives:
To define the complications and long-term outcomes of anticoagulant therapy for BPVT.

Methods:
Retrospective matched cohort study of patients treated with warfarin for presumed BPVT at a single center from 1999 to 2016. Controls with normal bioprostheses by echocardiography were matched 2:1 for age at implantation, gender, prosthetic valve position, and type of prosthesis (porcine / pericardial).

Results:
A total of 83 presumed BPVT patients (40 aortic, 21 mitral, 18 tricuspid, and 4 pulmonary) and 166 controls were included. Age at BPVT diagnosis was 60±19 yrs (41±41 months post implantation); 45 (54%) were male. Transvalvular gradients returned to baseline in 63 (76%) of the patients, after 5±4 months of warfarin; 60 (72%) patients were maintained on warfarin indefinitely. Recurrent BPVT was seen in 13 (16%) patients, 33±31 months after initial therapy. When compared to controls, warfarin-treated BPVT patients had similar incidence of stroke [4(5%) vs 5 (3%), p=0.49], peripheral embolic events [4(5%) vs 10 (6%), p=0.78)], and death [12 (14%) vs 28 (17%), p= 0.72] (Figure, left panel), but more bleeding requiring transfusion [18 (22%) vs 3 (2%), p<0.0001]. Presumed BPVT patients more often required surgical or percutaneous valve re-replacement (Figure, center panel); this difference persisted even when comparing only patients with confirmed BPVT (those who responded to anticoagulant therapy) vs. their matched controls (Figure, right panel).

Conclusion:
Warfarin anticoagulation for presumed BPVT is successful in the majority of patients, without increase in stroke, peripheral embolism or death, but at the cost of excess bleeding. Recurrent BPVT occured in 16% of patients. Importantly, patients with BPVT required more often valve re-replacement. This finding suggests that anticoagulant therapy does not fully restore prosthetic valve durability, and that BPVT patients should be closely monitored.
Abstract 16853: Peer Relationships of Children With Critical Congenital Heart Defects
Authors: Vannatta Kathryn , Quade Emeric , Kelleher Jennifer , Mah May Ling , Jackson Jamie L
Published: April 2024

Introduction:
Neurodevelopmental and executive functioning deficits place survivors of critical congenital heart defects (CHD) at risk for poor adaptive outcomes. Peer relationships play a critical role in development, but have received little scientific attention in CHD. Brief, general ratings of ‘social problems’ by children and parents inconsistently identify difficulties, but lack the rigor and specificity of school-based sociometric methods that identify impairment in other children with acquired brain injury. Our objective was to compare the peer interactions and social adjustment of CHD survivors to healthy control classmates (CC) using school-based methods.

Hypothesis:
CHD survivors would be higher in victimization, isolation, and disruptive behavior, lower in peer acceptance and mutual friendships than CC.

Method:
Data were collected in the classrooms of 34 children (9-12 yoa, 68% male) with critical CHD (dTGA, TOF, HLH/SVA, coarctation of aorta). One CC, matched for gender and age, was identified per class. Classmates with parental consent (N=723, 89% available) rated each other using the Extended Class Play (ECP; nominations of social and nonsocial attributes), Peer Acceptance Ratings (1-5, “like a lot” to “don’t like a lot”), and named Three Best Friends. Self-ratings were made on the PROMIS Peer Relationships scale. Teachers completed the Teacher Report Form (TRF). Independent two-tail t-tests compared the CHD and CC groups.

Results:
CHD survivors were higher in Victimization (
d
= 0.76, p = 003) and Isolation (
d
= 0.46,
p
= .063) but not Aggressive-disruptive behavior (
d
= 0.09, p = .674) on the ECP. CHD survivors had fewer mutual friends (
d
= -0.62,
p
= .015) but not lower Peer Acceptance (
d
= 0.24,
p
= 325). The ECP found that CHD survivors were seen as doing worse academically (
d
= -0.61,
p
= .014) and athletically (
d
= -0.99,
p
= .000) than CC, but not seen as more “ill” (tired, sick, or absent) (
d
= -0.30,
p
= .215). Differences on the PROMIS were not found. TRF for the CHD group suggested Social Problems (
M
T
= 55.6) and Academic deficits (
M
T
= 45.4) but not Internalizing (
M
T
= 51.4) or Externalizing (
M
T
= 51.2) behavior.

Conclusion:
Peer relations of children with critical CHD are a concern, may signal further developmental risk, and warrant more study.
Abstract 16862: Hypertrophic Cardiomyopathy in Octogenarians: Is Age Just a Number?
Authors: Papoutsidakis Nikolaos , Rodonski Anna , Williams Christina , Scanlon Irene , Brescia Carol , Jacoby Daniel
Published: April 2024

Introduction:
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and is typically diagnosed in youth or early adulthood. The clinical characteristics of hypertrophic cardiomyopathy among the very old have not been described.

Methods:
This is a single-center, retrospective observational study. We queried the Yale Inherited Cardiomyopathies database, obtaining data on HCM patients that were 80 years or older at time of inclusion (5/1/2018) or time of death. Care was taken to exclude patients with other diagnoses that could mimic the HCM phenotype.

Results:
Results are presented in Table 1. The majority had non-obstructive disease with apical hypertrophy in a substantial majority. All had echocardiographic diastolic dysfunction with concurrent symptomatic heart failure (NYHA II-IV). LA enlargement was substantial with mean LA ESV index of 53.2+-37.5 ml/m2. Atrial fibrillation was common (50%). High risk features such as SCD, ventricular arrhythmias and extreme hypertrophy were absent from this cohort, although syncope and family history of SCD were reported. Genetic test yield was 33%.

Conclusions:
Non-obstructive HCM with diastolic dysfunction, symptomatic heart failure, and arrhythmia are common among the very old with HCM. These features may reflect a combination of age related diastolic dysfunction and inherited HCM. Despite excellent survival symptomatic structural heart disease, arrhythmia, and stroke risk was the norm. The male:female ratio >1 usually seen in HCM is reversed, suggesting some degree of survival bias. Genetic testing remains useful in this age category. In summary, although HCM is not incompatible with reaching advanced old age, diastolic dysfunction drives significant HCM related morbidity.
Abstract 16863: Cardiac Magnetic Resonance T1 Mapping as a Window Into the Myocardium in Friedreich Ataxia
Authors: Lin Kimberly Y , Delatycki Martin , Corben Louise , Cheung Michael , Ferrari Victor , Fogel Mark , Moir Stuart , Peverill Roger
Published: April 2024

Introduction:
Left ventricular (LV) remodeling and hypertrophy are common findings in Friedreich Ataxia (FA) and associated with a poorer prognosis. Cardiac magnetic resonance (CMR) T1 mapping, a technique used to assess myocardial fibrosis, may be able to identify cardiomyopathic changes in FA at an early stage of the cardiac disease process. We hypothesized that T1 mapping variables would demonstrate myocardial involvement in FA independently of the recognized LV structural and functional changes.

Methods:
A standardized CMR protocol including T1 mapping and measurements of LV mass, LV end-diastolic volume, native T1 time, post gadolinium (PostGad) T1 time, and calculation of the LV mass/volume ratio (LVMVR), partition coefficient (PC), and extracellular volume (ECV) was performed at two sites on FA subjects who were homozygous for GAA repeats in the
FXN
gene. GAA repeat length in the shorter allele (GAA1) of the frataxin gene (
FXN
) was used as a surrogate for the degree of frataxin deficiency.

Results:
Ninety-five FA subjects (56% males, median age 22 yrs, age of onset 10 yrs, GAA1 700) were scanned. Nine FA subjects had a LV ejection fraction (EF) <55%; their T1 variables were not different than those with preserved LVEF. Fifty-three subjects had an elevated LVMVR (>1.20); their T1 variables were not different from those without an elevated LVMVR. On multivariate analysis, GAA1 correlated with native T1 time (p=0.009), PostGad T1 time (p=0.003), PC (p<0.001), and ECV (p<0.001) after adjusting for sex, age and site. LVMVR was a correlate of native T1 time when adjusted for sex, age and site (p=0.019), but not when also adjusted for GAA1, whereas GAA1 still predicted native T1 when adjusted for sex, age, site, and LVMVR (p=0.018).

Conclusion:
T1 mapping provides information about the myocardium in FA which is correlated with the degree of frataxin deficiency and is independent of LV remodeling. Study of the relationship between T1 variables and cardiac outcomes is now needed to help determine the utility of this technique as a monitoring and prognostic biomarker for this rare disease.
Abstract 16865: Debunking the Concept That the “Metabolically Obese Normal Weight” Phenotype is Independent of Fat: It is All About Central Obesity
Authors: Medina-Inojosa Jose R , Batsis John , Saeidifard Farzane , Maugeri Andrea , Homolka Martin , Allison Thomas , Bonikowske Amanda , Vinciguerra Manlio , Lopez-Jimenez Francisco
Published: April 2024

Background:
The Metabolically Obese Normal Weight (MONW) phenotype has been described as a unique subgroup of individuals with metabolic dysregulation similar to obese individuals, but not considered obese
per se
. In theory, these individuals have an adiposity-independent substrate predisposing them to metabolic dysregulation. We tested whether central obesity explains the metabolic abnormalities in persons with MONW in a prospective population-based cohort in the Czech Republic.

Methods:
We used data from Kardiovize Brno 2030 study, a prospective community-based cohort in Central Europe. We defined obesity using World Health Organization categories for body mass index (BMI) and central obesity by waist circumference (WC≥ 94 cm in men and ≥ 80 cm in women). Metabolically obese (MO) was defined using AHA criteria by having three or more of the following: Hypertriglyceridemia (≥ 1.7 mmol/l); HDL cholesterol level <1.0 mmol/l in men or <1.3 mmol/l in women; elevated blood pressure (systolic ≥ 130 mmHg and/or diastolic ≥ 85 mmHg) or antihypertensive drug treatment or history of hypertension; elevated fasting plasma glucose ≥ 5.6 mmol/l; or drug treatment and central obesity.

Results:
Of the 2,056 participants (46% men; mean age= 47.2 years, SD=11.2) included in the current analysis, 975 (47.4%) had normal weight and 696 (33.8%) were overweight. Prevalence of MO in the overall sample was 20.6% (n=424), 3.7% (n=36) among those with normal BMI and 9.9% (n=204) among overweight individuals. From the 36 subjects with MONW, 33 (91.6%) had central obesity by WC, while 201/204 (98.5%) with metabolically obese overweight, had central obesity by WC. Remarkably, in a subgroup of people with no metabolic obesity factors nobody had central obesity, see
Figure
.

Conclusions:
Metabolic dysregulation in people labeled as MONW can be explained by excessive visceral adiposity and not by an inherent predisposition, independent of adiposity.These findings underscore the importance of identifying central obesity in clinical practice even if BMI is below the obese criteria.
Abstract 16866: Sex Differences in Access to Care Before Acute Myocardial Infarction: Does the Health Care System Matter?
Authors: Raparelli Valeria , Pilote Louise , Krumholz Harlan M , Dreyer Rachel P
Published: April 2024

Introduction:
Access to high-quality health care for young women with acute myocardial infarction (AMI) lags behind that of men. Whether access to care varies based on the health care system remains unknown. We evaluated sex differences in pre-AMI access to care in young patients with AMI across countries.

Methods:
We utilized data from the GENESIS-PRAXY and VIRGO cohorts, which included young (
<
55 yrs) AMI patients hospitalized in countries with public (Canada, Spain, Australia) or private (United States [US], Switzerland) health care systems (2009-13). We collected data on demographics, CV risk, and psychosocial factors. Pre-AMI access to care was defined as: having a primary health care provider, difficulties in access to primary/specialist care, primary health care visits/diagnostic tests for cardiac symptoms (12 months prior to AMI). Sex-stratified analysis by health care system was performed.

Results:
Among 4,689 AMI patients (58% women, mean age 47±6 yrs), 64% were from the US and 22% from Canada. Compared with men, women had more CV risk factors, higher rates of depression/stress and lower socioeconomic status (SES) (Table); more strikingly in the US. Across countries, 70% of patients had a primary health care provider. However, women experienced more difficulties accessing primary (21% vs. 15%) or specialist care (27% vs. 20%, all p<.001) versus men. Women in the US reported cost barriers (47% vs. 5%), whereas women from other countries had difficulties in contacting primary health care providers (91% vs. 46%, all p<.001). Nevertheless, compared with men, women reported more primary health care provider visits (46% vs. 37%) and tests for cardiac symptoms (66% vs. 50%), regardless of health care system.

Conclusions:
In both public and privately funded health care systems, one-fifth of young AMI patients had poor pre-AMI access to care, despite a high-risk factor burden - especially among women in the US. Young women of low SES should be targeted for primary prevention.
Abstract 16876: Saturated Arterial Vasoconstriction in the Fontan Circulation
Authors: Saiki Hirofumi , Kuwata Seiko , Takanashi Manabu , Sugamoto Kenji , Senzaki Hideaki
Published: April 2024

Background:
Cardiac afterload in the Fontan circulation is enhanced due to sequentially connected pulmonary circulation to the systemic circulation. As the augmentation of afterload, which includes both of venous and arterial components, markedly compromise stroke volume in the Fontan patients, identification of primary culprit is vitally important to determine therapeutic targets in preserving circulation and end-organ function. We tested our hypothesis that the augmentation of cardiac afterload in the Fontan circulation is attributed by the compensative arterial constriction in addition to the venous congestion.

Methods:
Transient inferior vena-caval occlusion (IVCO) was applied to induced venous congestion in 23 Fontan and 87 postoperative biventricular circulation patients(BVC), and augmentation of arterial elastance (Ea) was measured with constructing ventricular pressure-volume relationship.

Results:
As compared with BVC patients, lower cardiac output in the Fontan patient was attributed by the augmented afterload with similar contractile function. While increase of CVP was augmented in the Fontan pts as compared to those with BVC (p=0.0016), increase of Ea was similar in both groups, suggesting suppressed response of increasing Ea in the Fontan pts. This was further supported by the negative relationship between CVP increase and Ea augmentation (p=0.048). Consistent with this, increase of Ea by induced venous congestion was negatively correlated with mean circulatory filling pressure (p=0.025) as well as systemic vascular resistance (p=0.047). Importantly, augmentation of Ea was independent of renin-angiotensin-aldosterone system (RAAS).

Conclusions:
Augmentation of afterload by induced venous congestion was rather saturated in the Fontan circulation, suggesting chronic activation of excessive compensatory vasoconstriction at baseline, which involves entire vascular system. As this response was independent of RAAS activity, in addition to RAAS blockade, structural and functional interventions to suppress cardiovascular remodeling should be implemented for the further reduction of cardiac afterload.
Abstract 16888: Comparing Adverse Clinical Outcomes Between Drug Eluting Stents and Bare Metal Stents in Patients Undergoing Non-Cardiac Surgery: a Meta-Analysis
Authors: Ranka Sagar , Joshi Udit , Poudyal Abhushan , Rawal Harsh , Kolkailah Ahmed A , Siddamsetti Sisir , Munoz Ezequiel , Sreenivasan Jaykumar , Parekh Jai , Fugar Setri , Sleiman Jose
Published: April 2024

Introduction:
History of coronary stents is risk factor for short term adverse clinical events (ACE) after a non-cardiac surgery (NCS). Safety of Drug-Eluting Stent (DES) or Bare-Metal Stent (BMS) has been studied in such patients, but no clear optimal choice of stent type exists. Thus, we performed a meta-analysis to compare the two stents in patients undergoing NCS.

Methods:
PubMed, Medline, EMBASE databases were queried from inception to January 2018 for all studies comparing DES vs BMS in patients undergoing NCS. ACE was defined as 30-day event rate of myocardial infarction (MI) or death after NCS. Two subgroups created by difference in time from stent placement to NCS: Within 30-45 days and >45 days after stent placement. Random effect model was used to estimate the odds ratio (OR). Two tailed p value < 0.05 were considered significant.

Results:
Four retrospective cohort studies with 6708 patients were identified. Out of 2597 BMS patients, 8.9% had an ACE compared to rate of 6.5% ACE in DES patients (n=4111). In the overall cohort, there was no difference was observed with either stent type irrespective of duration of NCS after stent placement (OR: 0.85, 95% CI 0.70-1.03, P=0.46). In patients undergoing NCS shortly(30-45days) after stent placement, no significant difference in ACE was observed {Odds Ratio (OR): 0.90, CI 0.63-1.28, P=0.82}. Similarly, no difference was noted in ACE in patients undergoing NCS after 45 days of stent placement (OR: 0.88, CI 0.56-1.40, P=0.10).

Conclusion:
In patients undergoing NCS after coronary stenting, there is no difference in rate of ACE with BMS vs DES placement. Thus, choice of stent may not play a role in prediction of adverse clinical outcomes after an non-cardiac surgery.