bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12512: Combination of Global Longitudinal Strain and Late Gadolinium Enhancement Predicts Improvement of Systolic Function After Aortic Valve Replacement in Patients With Severe Aortic Stenosis
Authors: Fujimiya Tsuyoshi , Iwai-Takano Masumi , Igarashi Takashi , Takase Shinya , Yokoyama Hitoshi
Published: April 2024

Introduction:
Myocardial fibrosis correlates with post-operative prognosis in patients with severe aortic stenosis (AS). There were a few reports that global longitudinal strain (GLS) by echocardiography decreased and correlated with myocardial fibrosis and/or late gadolinium enhancement (LGE) by MRI in patients with AS. However, it remains unclear whether GLS and LGE are possible to predict improvement of myocardial function after aortic valve replacement (AVR).

Hypothesis:
The combination of GLS and LGE identify the systolic dysfunction including myocardial fibrosis in severe AS, and predicts the improvement of systolic function after AVR.

Methods:
In 27 patients with severe AS before AVR, we examined GLS by 2D speckle tracking echocardiography and LGE by MRI for assessment of myocardial fibrosis, i.e., LGEcore(g): >mean of normal area +5SD, LGEgray(g): mean of normal area +2~5SD, and LGEcore+gray(g): LGEcore+LGEgray. In addition, fibrosis index (FI, %), as the percentage of fibrosis in myocardial specimen, was calculated in 11 patients. We evaluated the relationship among the GLS, the LGEs and the FI. Moreover, at 1 year after AVR, we assessed which indices in pre-operative period related to the improvement of GLS.

Results:
The mean values of indices were: GLS -15.6±0.9%, LGEcore 5.0±1.3g (4.5±1.2%), LGEgray 12.5±1.9g (11.5±1.4%), LGEcore+gray 17.5±3.0g (16.1±2.4%) and FI 7.1±1.4%. The FI related with the GLS (R=0.60, P<0.05), the LGEcore (R=0.58, P<0.05), and the LGEcore+gray (R=0.54, P<0.05). On the other hand, the GLS related to the LGEcore (R=0.50, P<0.05), LGEgray (R=0.52, P<0.05) and the LGEcore+gray (R=0.60, P<0.01). After AVR, the GLS was significantly improved (-15.0±1.2 to -18.6±1.1%, P<0.05). The LGE core before AVR was significantly smaller in the improvement group (GLS≥-19.0%) than the un-improvement group (GLS<-19.0%) (1.3±0.4 vs 7.1±2.5g, P<0.05).

Conclusions:
In patients with severe AS, GLS before AVR related with the mild to severe myocardial fibrosis. Moreover, the patients with severe fibrosis did not show the improvement of GLS in follow-up period. The combination of GLS and LGE will identify the potential systolic dysfunction including myocardial fibrosis, and predicts the improvement of systolic function after AVR.
Abstract 12515: Short- and Long-term Prognosis of Adaptive Servo Ventilation Therapy for Patients With Heart Failure With Preserved Ejection Fraction
Authors: Umeyama Atsushi , Takama Noriaki , Kazuyoshi Toda , Kurabayashi Masahiko
Published: April 2024

Introduction:
In Japan, Adaptive Servo Ventilation (ASV) is usually used for heart failure patients with sleep disordered breathing. However, SERVE-HF trial showed that ASV therapy could not reduce mortality and morbidity in patients with heart failure with reduced ejection fraction (HFrEF) in addition to optimized medical care in spite our data conflicting findings concerning these results. However, there is no data whether ASV therapy shows effectiveness and safety for patients with heart failure with preserved ejection fraction (HFpEF).

Hypothesis:
Our aim is to estimate short- and long-term prognosis of ASV therapy for patients with HFpEF compared with standard optical medical therapy.

Methods:
After medical therapy was optimized, a total of 157 consecutive HFpEF patients were divided into 2 groups. Fifty-six patients were tried to initiate ASV therapy (Group A), and 101 patients were categorized into optimal medical therapy (Group M). We estimate the short- (1-year) and long-term (average observational period: 1140±778 days) prognosis of ASV therapy for patients with HFpEF.

Results:
Short-term prognosis showed that ASV was equally effective and safe therapy for patients with HFpEF (Survival rate: Group A: 94.6%, Group M: 93.07%, p=0.699) (Figure 1A). On the other hands, long-term prognosis showed that ASV therapy had a tendency to fall into high fatal cardiovascular event rate (Group A: 19.6%, Group M: 9.9%, p=0.086) (Figure 1B). Especially, Group A with high central sleep apnea {central apnea index (CAI) ≧10/h} showed significant higher fatal cardiovascular event rate (CAI ≧10/h: 35.7%, CAI <10/h: 14.3%, Group M: 9.9%, p=0.029) (Figure 1C).

Conclusions:
Our results showed that short-term ASV therapy was effective and safe for patients with HFpEF compared with optimal medical therapy. On the other hands, long-term ASV therapy had limited effectiveness against HFpEF.
Abstract 12519: Identification of Novel Atrial Fibrillation Risk Factors in The Women’s Health Initiative Database Utilizing the Random Generalized Linear Model
Authors: Parizo Justin , Perez Marco
Published: April 2024

Introduction:
Atrial fibrillation (AF) is the most common cardiac arrhythmia and confers significant risk of morbidity and mortality. The etiology of AF remains incompletely understood. The Women’s Health Initiative (WHI) provides an opportunity to evaluate an extensive and diverse set of covariates in a large population to identify novel risk factors.

Hypothesis:
We hypothesized that we would validate existing predictors of AF and discover novel markers associated with AF using a random generalized linear model (RGLM).

Methods:
A training subset of women enrolled into the WHI without pre-existing AF were included. Women were followed for AF using self-report and medical records coding. 104 demographic, medical history and environmental exposure covariates were selected for analysis in a RGLM. RGLM is a bootstrapped aggregated generalized linear model (GLM) that combines the predictive accuracy of random forests, a machine-learning algorithm, with the interpretability of forward selected GLM’s. Variables that are most commonly found in the best-performing regression models with randomly generated covariates are determined the most influential.

Results:
Of the 60,000 women included in this training set, 5,047 developed AF over an average of 16.3 years. The women were on average 61.9 years old at enrollment, 1.7% were African American, 0.9% were Hispanic, 35.2% had hypertension and 4.2% had diabetes. The RGLM generated 100 sub-cohorts with 75 covariates through random sampling. The top 50 covariates, based on correlation with incident AF, were evaluated by forward selection to generate GLM’s. The variables identified by the RGLM as being the most influential predictors were history of leukemia, prior pregnancy, systolic blood pressure, waist circumference, history of DVT, depression, and vegetable consumption.

Conclusions:
Using RGLM, we validated several established risk factors for AF. We also, for the first time in a large population cohort, identified history of leukemia as an influential risk marker of AF. Additional study will be needed to determine if leukemia-specific chemotherapy mediates this association. Finally, these novel markers will need to be validated in additional cohorts.
Abstract 12528: ALR Protein, a Critical Protein in Cardiac Development, Regulates Cellular Iron Homeostasis by Modulating Mitochondrial Transport of ATP-Binding Cassette (ABC)-B8
Authors: Chang Hsiang-Chun , Jiang Xinghang , Senyei Grant , Shapiro Jason S , Sawicki Konrad T , Ardehali Hossein
Published: April 2024

Introduction:
Iron is an essential molecule for normal cellular physiology, and altered cellular iron homeostasis is commonly observed in diseases with disruption of iron/sulfur (Fe/S) cluster maturation, such as cardiomyopathy associated with Friedreich’s ataxia. Inhibition of Augmenter of Liver Regeneration (ALR), a mitochondrial inter-membrane-space protein involved in mitochondrial protein import, results in cardiac developmental defect in zebrafish, and its deletion is associated with increased oxidative stress and cytosolic Fe/S cluster maturation defects. ABCB8 is one of only two mitochondrial membrane proteins known to regulate cytosolic Fe/S cluster maturation. We hypothesized that ALR is critical for cytosolic Fe/S cluster maturation and iron homeostasis by regulating mitochondrial import of ABCB8.

Results:
Downregulation of ALR
in vitro
resulted in reduced cytosolic Fe/S cluster-containing enzyme activities and increased cellular iron uptake. Using a knockdown-rescue approach, we further demonstrated that only the mitochondrial, but not the cytosolic, ALR isoform is involved in the maturation of cytosolic Fe/S clusters. Because Fe/S clusters are synthesized in the mitochondria, we then assessed whether ALR can alter the levels or activity of ABCB7 and ABCB8, the two mitochondrial proteins known to regulate the maturation of cytosolic Fe/S clusters. Downregulation of ALR reduced the mitochondrial levels of ABCB8, while ABCB7 levels were not affected. We also identified defects in mitochondrial transport of ABCB8 as the mechanism for reduced mitochondrial ABCB8 levels with ALR knockdown. Finally, we demonstrated that ABCB8 physically interacts with the protein import system consisting of ALR and Mia40, thus providing a mechanism for reduced ABCB8 mitochondrial transport with ALR downregulation.

Conclusion:
Our results indicate that ALR and its interaction partner Mia40 are involved in the transport of ABCB8 into the mitochondria, which in turn regulates cytoplasmic Fe/S cluster maturation. These findings provide insights into cellular iron regulation, with implications in cardiovascular disease and cardiac development.
Abstract 12530: Tristetraprolin-mediated mRNA Degradation of Mitochondrial Electron Transport Chain Proteins Protects the Heart Against Iron Deficiency
Authors: Sato Tatsuya , Chang Hsiang-Chun , Martínez-Pastor María T , Puig Sergi , Bayeva Marina , Blackshear Perry , Wilsbacher Lisa D , Ardehali Hossein
Published: April 2024

Introduction:
Iron deficiency is the most common nutrient deficiency in the world, and cells respond to iron deficiency by activating iron regulatory proteins (IRP) to increase cellular iron uptake and availability. Although iron overload can cause cardiomyopathy, iron deficiency does not normally lead to cardiac damage. Tristetraprolin (TTP) is a tandem zinc finger protein that binds to the AU-rich elements (AREs) in the 3’ untranslated regions (UTR) of mRNA molecules and causes their degradation. We recently showed that TTP plays a role in iron conservation in the cell by targeting and degrading the mRNA for the iron importer, transferrin receptor 1. However, it is not clear how cells respond to conditions when cellular iron uptake and availability are not sufficient to match the demand. We hypothesized that TTP protects against cardiac dysfunction under iron deficiency by targeting the mRNAs of Fe/S cluster-containing proteins in the mitochondria.

Results:
To assess the effects of TTP on mitochondria, we first performed an unbiased in silico screen and identified a number of mRNAs that contain the consensus TTP-binding sequence in their 3’ UTR. Of those, steady-state levels of several mRNAs were increased with TTP deletion. However, only the mRNAs of three genes were shown to be bound by and be degraded by TTP protein: NDUFS1 in complex I, UQCRFS1 in complex III and mitochondrial aconitase. Interestingly, these proteins need Fe/S clusters to be active, suggesting that their protein levels are decreased in the absence of Fe/S cluster availability. We also demonstrate that in the absence of TTP and with iron deficiency, complex III gets formed with UQCRFS1, but without the required Fe/S cluster, which leads to the production of reactive oxygen species (ROS) and cellular injury. Finally, mice with systemic deletion of TTP display cardiac dysfunction under iron deficiency, demonstrating a major role for TTP in maintaining normal cellular function under iron deficiency.

Conclusions:
Our results provide a pathway that is activated in parallel to the IRPs and leads to degradation of mitochondrial mRNAs that require Fe/S clusters. This response to iron deficiency is critical to prevent excessive ROS production and cardiac damage.
Abstract 12544: Evidence for Involvement of Inflammatory Changes of Perivascular Adipose Tissue in the Pathogenesis of Coronary Hyperconstricting Responses Induced by Drug-Eluting Stent in Pigs in vivo -Impact of Fluorodeoxyglucose Positron Emission Tomography Imaging
Authors: Ohyama Kazuma , Matsumoto Yasuharu , Amamizu Hirokazu , Uzuka Hironori , Nishimiya Kensuke , Morosawa Susumu , Hirano Michinori , Watabe Hiroshi , Funaki Yoshihito , Takahashi Jun , Ito Kenta , Shimokawa Hiroaki
Published: April 2024

Background:
Recent studies suggested that perivascular adipose tissue (PVAT) play important roles as a source of various inflammatory mediators in the pathogenesis of cardiovascular disease. We thus tested our hypothesis that inflammatory changes in the coronary PVAT are associated with coronary hyperconstricting responses after drug-eluting stent (DES) implantation by using FDG PET.

Methods:
Everolimus-eluting stents (EES) were randomly implanted in pigs into either the left anterior descending or circumflex coronary artery while non-stented artery was used as a control. After 1 month, coronary vasoconstricting responses to intracoronary serotonin were examined by coronary angiography in vivo, followed by FDG PET/CT ex vivo imaging and autoradiography for measurement of FDG uptake.

Results:
Coronary vasoconstricting responses were significantly enhanced at the edges of the EES site compared with the control site (P<0.01, n=40) (Figures A-C). Notably, FDG PET/CT imaging showed enhanced FDG uptake at the EES-implanted coronary segment with significant association between the target to background ratio and the extent of coronary vasoconstricting responses (P<0.01) (Figures D-F). In addition, autoradiography showed that the FDG accumulation was markedly enhanced at the edge of the EES site compared with the control site and was significantly associated with the extent of coronary vasoconstricting responses (P<0.01) (Figures G-J, O). Furthermore, histological analysis and RT-PCR showed that the extent of inflammatory changes in the coronary PVAT were significantly enhanced at the edges of the EES site compared with the control site (Figures K-N).

Conclusions:
These results demonstrate for the first time that inflammatory changes in the coronary PVAT are involved in the pathogenesis of DES-induced coronary hyperconstricting responses in pigs in vivo and that FDG PET imaging may be useful for assessment of coronary PVAT inflammation.
Abstract 12557: The Impact of Spinal Cord Injury and Exercise Training on Cerebrovascular Function: Preliminary Results
Authors: Kim Dong-Il , Lapointe Matthew , Hamner Jason W , Taylor J. Andrew , Tan Can Ozan
Published: April 2024

Background:
Spinal cord injured (SCI) individuals are at higher risk of cerebrovascular disease, including stroke, suggesting that they cannot maintain steady cerebral perfusion. This may be due to disruption of nervous vascular control and/or prolonged inactivity and consequent deconditioning. If inactivity plays a significant role, appropriate exercise may reverse this decline. However, the relation between SCI and cerebrovascular function, and the impact of exercise is not well established.

Methods:
We studied cerebral blood flow responses to progressive increases in arterial CO
2
(via rebreathing) in 9 individuals with SCI (C5 - T10, >7 months post-injury). Vasoreactivity was derived from the relation between end-tidal CO
2
and cerebrovascular conductance. Five of the individuals were enrolled in 3-months hybrid-functional electrical stimulation-rowing exercise training program.

Results:
Vasoreactivity was somewhat lower in individuals with SCI compared to able-bodied controls (0.021±0.003 vs 0.030+0.009,
p
=0.28), and was related to the level of injury (R
2
=0.51,
p
=0.03), such that individuals with higher level injuries had lower vasoreactivity. Exercise training improved vasoreactivity (by ~25% overall), and the extent of improvement was strongly related to injury duration (R
2
=0.70,
p
=0.07) but not level (R
2
=0.06), such that longer injury duration was associated with a bigger improvement.

Conclusions:
Given that individuals with higher injuries are more inactive compared to those with lower injuries, these preliminary data suggest that the decline in cerebrovascular function after SCI may primarily be due to prolonged inactivity and may be reversed by appropriate exercise. These results may have implications for sustained physical inactivity and cumulative cerebrovascular risk in general population.
Abstract 12575: Cellular Basis of C-Type Natriuretic Peptide Produced Augmentation on Left Ventricular Systolic and Diastolic Functional Performance in Heart Failure
Authors: Zhang Zhi , Zhang Xiaowei , Li Tiankai , Cheng Heng-Jie , Zhou Peng , Cheng Che Ping
Published: April 2024

Background:
In addition to its well-known vasodilating and natriuretic actions, C-type natriuretic peptide (CNP), has been viewed as an endogenous inhibitor of the renin-angiotensin system, but its direct cardiac effects remain controversial. In heart failure (HF), circulating and myocardial CNP levels are increased, which may alter LV functional response to CNP. However, the alterations and cellular mechanisms of CNP-induced cardiac response in HF remain unclearly defined. We assessed the hypothesis that in HF, CNP might produce enhanced positive modulation on myocyte [Ca
2+
]
i
transient ([Ca
2+
]
iT
) and L-type Ca
2+
current (I
Ca,L
) and improve LV and myocyte functional performance.

Methods:
We assessed LV systolic and diastolic function and compared myocyte contractile, [Ca
2+
]
iT
, and I
Ca,L
responses to a clinically relevant dose of CNP (2 μg/kg bolus plus 0.4 μg/kg/min, iv, 10 min) in 12 normal (N) and 12 age-matched adult rats with isoproterenol (ISO)-induced HF (2 months after 170 mg/kg, sq, for 2 days).

Results:
In normal rats, CNP caused leftward shifts and increased slopes of P
ES
-V
ES
relations (E
ES
) (14%, 1.17 vs 1.04 mmHg/μl) with decreased LV time constant relaxation (τ, 19%, 9.0 vs 11.1ms). In HF rats, versus normal, CNP produced a significantly greater increase in E
ES
(37%, 0.81 vs 0.59 mmHg/μl) and a decrease in τ (31%, 11.0 vs 15.9 ms), indicating enhanced increases in LV contractility and the rate of LV relaxation. Consistently, in isolated myocytes, superfusion of CNP (5x10
-7
M) caused improved cell contraction and relaxation in both normal and HF myocytes. In HF myocytes, CNP resulted in significantly greater increases in the peak velocity of shortening (dL/dt
max
, 18%, 167.4 vs 141.9; 39%, 103.9 vs 74.9 μm/sec) and relengthening (dR/dt
max
, 19%, 134.7 vs 113.2; 71%, 92.1 vs 53.8 μm/sec) accompanied by significantly larger increases in [Ca
2+
]
iT
(9.5%, 0.23 vs 0.21; 29%, 0.22 vs 0.17) and I
Ca,L
(12%, 9.1 vs 8.1; 28%, 5.9 vs 4.6 pA/pF).

Conclusions:
CNP produces positive modulation on cardiac performance in both normal and HF rats. In HF, CNP caused greater improvement of LV and myocyte contraction, and relaxation with further augmentation of increased [Ca
2+
]
iT
and

I
Ca,L.
These findings support the usefulness of CNP as a new therapeutic option for HF.
Abstract 12580: Does Sex Influence the Effect of Surgical Revascularization in Patients in Ischemic Left Ventricular Dysfunction? Results From the STICH Trial
Authors: Zheng Qi , Cyrille Nicole , She Lilin , Szwed Hann , Lang Irene M , Farsky Pedro S , Castelvecchio Serenella , Biernat Jolanta , Paraforos Alexandros , Kosevic Dragana , Favaloro Liliana E , Nicolau Jose C , Varadaragan Padmini , Velazquez Eric , Pai Ramdas G , Lee Kerry , Desvigne-Nickens Patrice , Piña Ileana L
Published: April 2024

Introduction:
Studies have shown sex-specific differences regarding CAD and heart failure with left ventricular (LV) dysfunction. Whether these differences impact the benefit of CABG in patients with ischemic LV dysfunction has not been studied prospectively. Female sex is conventionally considered a risk factor for open-heart surgery, and has been included as a poor prognostic factor in multiple cardiac operative risk evaluation scores. We investigated the impact of sex on the long-term benefit of CABG in patients enrolled in the prospective Surgical Treatment for Ischemic Heart Failure Study (STICH) trial.

Method:
The STICH trial randomized 1212 patients [148 (12%) women and 1064 (88%) men] with CAD and EF≤ 35% to medical therapy alone (MED) versus MED plus CABG. Long-term (10-year) outcomes with each treatment were compared according to sex.

Results:
At baseline, women were older with higher BMI and more CAD risk factors (e.g. diabetes) except for smoking, and had lower rates of prior CABG than men (all p<0.05). Moreover, women had higher NYHA class, lower 6-min walk capacity and lower Kansas City Cardiomyopathy Questionnaire scores (all p<0.05). At 10-year follow up, the all-cause mortality rate (HR 0.70, CI 0.55-0.89, adjusted p=0.002) and CV mortality rate (HR 0.64, CI 0.48-0.86, adjusted p=0.006) were significantly lower in women than men. Furthermore, with randomization to CABG vs. MED treatment, there was no significant interaction between sex and treatment group in all-cause mortality, CV mortality, mortality or CV hospitalization (all p>0.05, Figure 1). In addition, surgical deaths were similar for both sexes among patients randomized to CABG.

Conclusion:
Sex does not impact the effect of CABG on all-cause mortality, CV mortality, CV hospitalization or surgical deaths in patients with ischemic LV dysfunction. Thus, sex should not influence treatment decisions regarding CABG in these patients.
Abstract 12607: Improvement in Skin Inflammation Associates With Improvement in Aortic Vascular Inflammation by 18-FDG PET/CT in Psoriasis
Authors: Dey Amit K , Lerman Joseph B , Aberra Tsion M , Chaturvedi Abhishek , Kabbany Mohammad T , Joshi Aditya A , Rodante Justin A , Silverman Joanna I , Dahiya Asha , Shukla Parag , Natarajan Balaji , Teague Heather L , Salahuddin Taufiq , Ng Qimin , Aridi Tarek Z , Playford Martin P , Lockshin Benjamin N , Ahlman Mark A , Chen Marcus Y , Gelfand Joel M , Mehta Nehal N
Published: April 2024

Introduction:
Inflammation is a risk factor for the initiation and progression of atherosclerosis. Psoriasis (PSO), a chronic inflammatory skin disease, is an emerging risk factor for cardiovascular (CV) disease. Indeed PSO severity is associated with increased vascular inflammation (VI) by 18-FDG PET/CT in vivo and with future CV risk. However, the longitudinal impact of changes in PSO severity on vascular disease is unknown.

Hypothesis:
We hypothesized that an improvement in PSO severity would associate with an improvement in VI by FDG PET/CT.

Methods:
Consecutively recruited PSO patients (N=102) underwent FDG PET/CT scans, and cardiometabolic profiling at baseline and 1-year. VI was assessed as target-to-background ratio (TBR) (Excellence Brilliant Workstation). PSO severity was measured as Psoriasis Area Severity Index (PASI) score. The longitudinal change in VI of the aortic arch was analyzed using unadjusted and adjusted multivariable regression.

Results:
The cohort was middle-aged, had a low CV risk by Framingham risk score and had mild to moderate PSO severity. At follow-up, patients had a median improvement in PASI score of 31.91% (p<0.001) with use of topical (67%), biological (62%) and UVB (16%) therapy. Aortic TBR in these patients improved (6.3%, p<0.001) (Table 1). Improvement in PASI score associated with an improvement in aortic arch TBR beyond adjustment for traditional CV risk factors, statin use, & systemic/biologic PSO therapy (β=0.21, p = 0.03).

Conclusions:
Improvement in PSO severity associated with an improvement in aortic VI by FDG PET/CT, suggesting that skin inflammation may present a modifiable risk factor to mitigate CV risk. This finding of a 6.3% decrease in VI with improvement in PASI score is of similar magnitude to that observed after low-dose statin therapy in coronary artery disease, suggesting control of remote inflammation may quell vascular disease progression. Larger studies are needed to confirm these findings.
Abstract 12609: Impaired Mitochondrial Respiration Precedes Clinical Heart Failure in Right Ventricular Pressure Overload
Authors: Sandeep Nefthi , Zhao Mingming , Hu Donq-Qing , Coronado Michael , Kooiker Kristina B , Fajardo Giovanni , Bernstein Daniel , Reddy Sushma
Published: April 2024

Introduction:
Congenital heart disease patients with right-sided obstruction have increased stress on the right ventricle (RV) leading to right ventricular hypertrophy (RVH) and failure (RVF). The critical role of mitochondrial energetics in the development of RVH and RVF is not known. We hypothesize that mitochondrial dysfunction contributes to the chronic energy deficit and mechanical dysfunction in heart failure.

Methods:
Adult, male FVB mice underwent pulmonary artery banding (PAB) to induce RVH (n=9) and RVF (n=4) and were compared to sham-operated controls (n=9). We used a high-resolution Oxygraph2K respirometer to measure oxygen consumption in tissue and in isolated mitochondria from the RV free wall. We evaluated leak respiration during substrate utilization by complex 1-NADH dehydrogenase and complex 2-succinate dehydrogenase and during maximal ATP generation by complex 5-ATP synthase. Groups were compared using ANOVA. Data is presented as mean ± SEM (*p<0.05).

Results:
All mice had a PAB gradient of 30-40 mmHg by echocardiography. RVH mice had preserved systolic function while RVF mice had heart failure (ascites, tachypnea, hepatomegaly) and decreased function (Table). RVH showed preserved complex 1 mediated respiration but lower complex 2 and 5 respiration and lower respiratory control ratios (RCR) while in RVF, all complexes showed impaired respiration (Table). However, isolated mitochondria from RVF demonstrated preserved respiratory capacity when supplied with exogenous substrates and no change in complex levels.

Conclusion:
Mitochondrial respiration is impaired even in stable RVH and progressively worsens in RVF in vivo. Interestingly, isolated mitochondria show normal respiration in RVF when supplied with substrates ex vivo suggesting a defect with substrate delivery rather than intrinsic mitochondrial function. Strategies to enhance substrate delivery may improve ATP generation and thereby preserve function in heart failure.
Abstract 12629: Endothelial Prolyl-4 hydroxylase 2 Deletion Induces Cardiac Hypertrophy and Heart Failure via Hypoxia Inducible Factor-2α Activation
Authors: Dai Zhiyu , Zhu Maggie M. , Gao Chen , Zhang Xianming , Zhao You-Yang
Published: April 2024

Background:
Cardiac hypertrophy is a common adaptive response to injury and stress, and can eventually lead to heart failure. The role of endothelial Prolyl-4 hydroxylase 2 (PHD2)/hypoxia inducible factors (HIFs) signaling in the pathogenesis of heart failure is unclear. We hypothesize that endothelial PHD2/HIF signaling dysfunction contributes to cardiac hypertrophy and heart failure.

Methods:
Mice with Tie2-Cre-mediated deletion of
Egln1
(encoding PHD2) (
Egln1
Tie2-Cre
), as well as double knockout mice with both
Egln1
and
Hif1a or
Egln1
and
Hif2a
were generated.

Egln1
f/f

bone marrow cells were transplanted to lethally irradiated

Egln1
Tie2-Cre

mice to determine the contribution of bone marrow cells in cardiac hypertrophy. Mice carrying
Egln1
f/f
were bred into Endo
SCL-
Cre-
ER(T)
mice containing tamoxifen-inducible
Cre
to generate mice with
Egln1
deletion only in endothelial cells in adult mice (

Egln1
SCL-Cre

) after tamoxifen injection. Echocardiography were measured to study cardiac size and function. Histological examination was also performed.

Results:

Egln1
Tie2-Cre

mice exhibited left ventricular hypertrophy evident by increased thickness of anterior and posterior wall and left ventricular mass, as well as cardiac fibrosis.
Egln1
deletion in bone marrow cells did not contribute to cardiac hypertrophy. Tamoxifen induced endothelial
Egln1
deletion in adult

Egln1
SCL-Cre

mice also induced left ventricular hypertrophy and heart failure. Genetic ablation of
Hif2a
but not
Hif1a
in

Egln1
Tie2

mice normalized cardiac size and function. Additionally, we observed a marked decrease of PHD2 expression in heart tissues from patients with dilated cardiomyopathy.

Conclusion:
This studies define for the first time an unexpected role of endothelial PHD2 deficiency in inducing cardiac hypertrophy and heart failure in a HIF-2α dependent manner. Thus, targeting PHD2/HIF-2α signaling represents a novel therapeutic approach for the treatment of heart failure.
Abstract 12641: Absolute Change in Troponin Outperforms Relative Change in Troponin for Discrimination of Acute Myocardial Infarction: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Arora Sameer , Kaul Prashant , Chang Patricia P , Rossi Joseph S , Hall Michael E , Rosamond Wayne D , Caughey Melissa C
Published: April 2024

Introduction:
The rise or fall of cardiac troponin plays a central role in classification of acute myocardial infarction (AMI) by the Third Universal Definition. Clinical Practice Guidelines (CPG) advocate using a 20% change in serial troponin measurements for AMI detection. However, it is uncertain whether absolute or relative change in troponin has greater diagnostic accuracy.

Hypothesis:
Absolute and relative change in troponin will have differing abilities to detect AMI in patients hospitalized with chest pain and elevated troponin.

Methods:
Since 1987, the ARIC study has conducted surveillance of hospitalized events in 4 US communities. Clinical and laboratory data were abstracted, including troponin values from 1996 onward. AMI was classified by ARIC with a validated algorithm, using elevated biomarkers, presence of chest pain, and ECG evidence. Our analysis was based on patients with chest pain and serial troponin measurements (day 1 and day 2 of hospitalization), with elevated troponin on day 1. Patients undergoing revascularization procedures <24 hours after event onset were excluded. The absolute and relative change in troponin between days 1 and 2 were calculated, and outcome discrimination was analyzed using the area under the receiver operating characteristic curve (AUC). All analyses were weighted by the inverse of the sampling probability.

Results:
A total of 6,232 hospitalizations spanning January 1 1996 - December 31, 2012 met our inclusion criteria. Most patients were white (64%) and male (60%), with a mean age of 63 years. Troponin I was more often assayed (93%) than troponin T. A total of 5,408 (87%) were classified as AMI by the ARIC algorithm, with 10% as STEMI. Absolute change in troponin outperformed relative change in troponin for detection of AMI (AUC: 0.69 vs. 0.64), NSTEMI (AUC: 0.68 vs. 0.64), and STEMI (AUC: 0.77 vs. 0.65); p <0.001 for all comparisons. The recommended 20% cut-point endorsed by CPG diagnosed AMI, NSTEMI, and STEMI similarly, with a sensitivity of 75% and specificity of 44%.

Conclusion:
In patients hospitalized with chest pain and elevated troponin, absolute and relative change in serial troponin values detected AMI with moderate diagnostic accuracy; however, absolute change in troponin was a better discriminator.
Abstract 12645: Coronary Sinus Biomarker Assessments in Non-ST Elevation Acute Coronary Syndrome: Systemic or Local Cardiac Release of High Sensitivity C-Reactive Protein?
Authors: Damen Sander A , Cramer Gilbert E , Aengevaeren Wim R , Oude Ophuis Ton J , Fokkert Marion J , Dikkeschei Lambert D , Dieker Hendrik-Jan , Gehlmann Helmut , Verheugt Freek W , Suryapranata Harry , Brouwer Marc A
Published: April 2024

Introduction:
High sensitivity C-reactive protein (hsCRP) is frequently elevated in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). However, controversy remains regarding the origin of hsCRP. Reported theories vary from a systemic increase in inflammatory status, to a more local process.

Purpose:
To assess concentrations of hsCRP in patients with ongoing NSTE-ACS using multiple sampling sites, to enable measurement of systemic or local changes.

Methods:
46 Troponin positive NSTE-ACS patients with significant coronary artery disease were included. Systemic arterial and venous blood was obtained, and right sided catheterization was performed to sample blood from the coronary venous system (CVS). In suitable patients, an additional blood sample was collected from the culprit coronary artery distal to the culprit lesion. Six hours post procedure blood was obtained from the systemic venous circulation. hsCRP concentrations were compared between the sampling sites.

Results:
The median hsCRP concentrations in the systemic arterial and venous blood were high and not significantly different. hsCRP concentrations in the CVS were significantly lower (table).The median hsCRP concentrations between blood collected from the culprit coronary artery distal to the culprit lesion and the systemic arterial circulation were not significantly different (4.56mg/L to 4.40mg/L, respectively, n=14; p=0.551). Systemic hsCRP concentrations six hours post procedure were significantly higher (5.66mg/L vs 4.86mg/L; p<0.001).

Conclusion:
In this series of patients with ongoing NSTE-ACS a decrease in hsCRP from the systemic circulation to the CVS was observed. This observation, combined with similar concentrations proximal and distal to the culprit and higher systemic concentrations six hours post procedure favors an extracardiac source of hsCRP.
Abstract 12657: Congenital Pseudoaneurysm of the Mitral-Aortic Intervalvular Fibrosa: A Case Report
Authors: Harrington Jamie K , Glickstein Julie , Shah Amee
Published: April 2024

Introduction:
The mitral-aortic intervalvular fibrosa (MAIVF) is the area of fibrous continuity between the mitral and aortic valves. Pseudoaneurysm formation can rarely occur here after trauma, commonly surgical or infectious. We describe the first case of a congenital pseudoaneurysm of the MAIVF (PMAIVF) seen prenatally as an isolated cardiac defect and followed conservatively postnatally.

Case Report:
A fetal echocardiogram was performed at 30 weeks gestation after an echogenic cardiac focus was seen on fetal ultrasound. A large left atrial mass with mixed echogenicity was seen oriented along the atrial septum with suggestion of flow in the lesion on color Doppler (Fig 1A-B). The mass was not obstructing mitral, aortic or foramen ovale flow and the rest of the cardiac anatomy was normal. A comparative view on the postnatal echocardiogram confirmed the presence of an echolucent mass with flow into the lesion on color Doppler (Fig 1C-D). The parasternal long axis demonstrated the neck of the aneurysm arising between the mitral and aortic annuli with lack of fibrous continuity (Fig 2A). Color Doppler demonstrated blood flow into the pouch during systole and into the left ventricular outflow tract during diastole consistent with a congenital PMAIVF (Fig 2B-C). Pulsed-Doppler showed antegrade and retrograde flow in the neck (Fig 2D). The infant is now 4 months old and serial echocardiograms have shown stable size and appearance of the PMAIVF, with low velocity bidirectional flow into the neck, and it has remained non-obstructive.

Conclusion:
PMAIVF can exist without preceding trauma as a rare, isolated congenital cardiac defect. The natural history of a congenital PMAIVF is unclear.
Abstract 12663: Ankle-brachial Index For Prognosis of Cardiovascular Disease in Patients With Mild Renal Insufficiency
Authors: Nishimura Hitoshi , Miura Takashi , Minamisawa Masatoshi , Ueki Yasushi , Abe Naoyuki , Hashizume Naoto , Mochidome Tomoaki , Harada Mikiko , Shimizu Kunihiko , Shoin Wataru , Yoshie Koji , Oguchi Yasutaka , Ebisawa Soichiro , Motoki Hirohiko , Izawa Atsushi , Koyama Jun , Ikeda Uichi
Published: April 2024

Background:
Low ankle-brachial index (ABI) is a known predictor for future cardiovascular events and mortality in patients with advanced stage chronic kidney disease (CKD) or undergoing hemodialysis. While most prior studies defined CKD as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m
2
, recent reports have demonstrated that cardiovascular risk may increase even in earlier stages of renal insufficiency. We hypothesized that low ABI may predict future cardiovascular morbidity and mortality in patients with mild impairment of renal function.

Methods:
The IMPACT-ABI study was a retrospective, single-center, cohort study that enrolled and obtained ABI measurements for 3131 patients hospitalized for cardiovascular disease between January 2005 and December 2012. From this cohort, we identified 1511 patients with mild renal insufficiency (eGFR = 60-89 ml/min/1.73 m
2
), and stratified them into two groups: ABI ≤ 0.9 (low ABI group; 9.3%) and ABI > 0.9 (90.6%). The primary outcome measured was the cumulative incidence of major adverse cardiovascular events (MACE: cardiovascular death, myocardial infarction, and stroke).

Results:
Over a mean follow-up of 5.1 years, 101 MACE occurred. The incidence of MACE was significantly higher in patients with low ABI than in those with ABI > 0.9 (29.7% vs. 14.3%, log rank P < 0.001). In multivariate Cox proportional hazard analysis adjusted for traditional cardiovascular risk factors, low ABI was an independent predictor of MACE (hazard ratio: 1.79; 95% confidence interval: 1.03-3.08; P = 0.036).

Conclusions:
Low ABI was an independent predictor for MACE in patients with mild renal insufficiency.
Abstract 12670: Variability in Radiation Dose and Image Quality: A Comparison Across Fluoroscopy-system Vendors and Generations of Equipment
Authors: Hill Kevin D , Carboni Michael P , Doyle Thomas P , Idriss Salim , Janssen Dana , Nicholson George , Sathanandam Shyam , Mann Steve , Fleming Gregory
Published: April 2024

Introduction:
Increased recognition of the potentially harmful effects of ionizing radiation has spurred technological advances to reduce exposure during fluoroscopy. However there is currently little understanding of the dose-image quality (IQ) relationship between fluoroscopy vendors and across generations of equipment used for imaging during pediatric catheterization.

Methods:
We evaluated latest generation fluoroscopy systems from Phillips, Siemens, GE and Toshiba, and an older generation Phillips system (2004 release). Fluoroscopy and cineangiography were performed on a tissue simulation anthropomorphic phantom using a standardized imaging approach. Phantom surface exposures were used for Monte Carlo simulations to calculate radiation effective dose, accounting for differences in beam parameters. We also imaged a fluoroscopy IQ phantom to assess contrast-detail and line-per-inch visualization. IQ images were scored by 3 blinded reviewers with scores averaged to produce a composite rating (scale 0-18). To assess the impact of imaging approach we then simulated a neonatal cardiac catheterization incorporating “typical” imaging protocols provided by institutions using the various systems.

Results:
Effective doses and IQ scores are summarized in the table. Effective doses varied by >400% with the older generation system consistently delivering markedly higher doses. The associated figure summarizes dose and IQ for a simulated neonatal cardiac catheterization which accounts for measured doses as well as the reported institutional imaging parameters summarized in the figure legend.

Conclusion:
These data demonstrate substantial technological improvements in fluoroscopy equipment and may be useful to justify institutional “upgrades”. Comparing latest generation systems across vendors and institutions, we found variability in the dose-IQ relationship that reflects both equipment and imaging approach.
Abstract 12684: Cpr Quality During Out- Of- Hospital Cardiac Arrest Transport
Authors: Cheskes Sheldon , Zhan Cathy , Byers Adam , Verbeek Richard , Drennan Ian , Lin Steve , Taher Ahmed , Brooks Steven , Buick Jason , Morrison Laurie J
Published: April 2024

Background:
Previous studies have demonstrated significant associations between cardiopulmonary resuscitation (CPR) quality metrics and survival to hospital discharge following out-of- hospital cardiac arrest (OHCA). No large study has explored the relationship between location of resuscitation (scene vs. transport) and CPR quality.

Objective:
We sought to determine the impact of CPR location on CPR quality metrics during OHCA.

Methods:
We performed a retrospective cohort study of prospectively collected data from the Toronto RescuNET Epistry- cardiac arrest database. We analyzed CPR quality data from all treated adult OHCA occurring over a 39 month period beginning January 1, 2013. We included OHCA patients who underwent resuscitation by emergency medical services and had CPR quality metric data for both scene and transport phases of the resuscitation. Based on 2010 American Heart Association guidelines, high quality CPR was defined as chest compression fraction (CCF)> 0.70, compression rate >100/min and compression depth > 5.0 cm. Scene and transport CPR quality metrics were compared for each patient using a Wilcoxon rank-sum paired-samples test . The proportion of patients who received high quality CPR (defined as meeting all 3 CPR quality benchmarks) was compared between resuscitation locations using a chi-square statistic.

Results:
Amongst 842 included patients (69.5% male, mean (SD) age 66.8±17.0), median compression rate was statistically higher on scene compared to transport (105.8 vs. 102.0 ; Δ 3.8; 95% CI: 2.5, 4.0), while median compression depth (5.56 vs. 5.33; Δ 0.23; 95% CI: 0.12, 0.26) and median CCF (0.95 vs. 0.87; Δ 0.08; 95% CI: 0.07, 0.08) were statistically higher during the transport phase. The proportion of patients with high quality CPR was similar on scene compared to during transport (45.8% vs. 42.5%; Δ 3.3; 95% CI: -1.4, 8.1).

Conclusions:
High quality CPR metrics were identified in both (scene and transport) locations of resuscitation and exceeded current CPR quality benchmarks. These results suggest that high quality, manual compressions can be performed by well-trained EMS systems regardless of location. Further study is required to determine whether these metrics can be replicated in other EMS jurisdictions.
Abstract 12778: 44 % of Patients With Myocardial Infarction are Silent Manifestation in Diabetics
Authors: Soejima Hirofumi , Morimoto Takeshi , Okada Sadanori , Sakuma Mio , Nakayama Masafumi , Jinnouchi Hideaki , Sugiyama Seigo , Waki Masako , Saito Yoshihiko , Ogawa Hisao
Published: April 2024

Background:
Diabetes mellitus is well known as a significant predictor of silent myocardial ischemia. The incidence rates of silent events with newly developed Q waves, (especially, silent myocardial infarction (SMI)) in diabetic patients, have yet to be elucidated. We sought to evaluate the prevalence and predictors of SMI in type 2 diabetic patients without a history of atherosclerotic events.

Methods:
The Japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) trial was performed to examine the efficacy of low-dose aspirin therapy for the primary prevention of atherosclerotic events in type 2 diabetes patients. Initially, there were no Q waves in any electrocardiograms (ECGs). The JPAD trial was a multicenter, prospective, randomized, open label, blinded, end-point study done from 2002 to 2008. After completion of the JPAD trial, we followed up the patients until 2015. ECGs of 1648 patients were re-examined to discover SMI in 2013 and 2015. We compared predictive factors for SMI to those for acute myocardial infarction (AMI).

Results:
During follow up of a median of 10.3 years, 64 patients suffered from a first AMI and 51 patients suffered from a first SMI. We novelly demonstrated that the incidence rate of SMI is comparable to that of AMI in diabetic patients (Figure). Age, smoking, dyslipidemia, and HbA1c ≥ 7.2 % were all associated with AMI. Hypertension was associated with SMI. Cox proportional hazards model analysis revealed that age ≥ 65 years and HbA1c ≥ 7.2 % were independent factors for AMI (P=0.0003, 0.0214, respectively, Figure). On the other hand, there were no significant independent factors for SMI.

Conclusions:
Our study demonstrates that age ≥ 65 years and HbA1c ≥ 7.2 % were independently associated with the incidence rate of AMI, but they were not associated with the incidence rate of SMI. Clinically, diabetic patients should frequently get ECGs for the detection of SMI because the rate of SMI is similar to AMI rates.
Abstract 12791: Heart Rate at One Minute Impact Neonatal Resuscitation & Clinical Outcomes in Infants
Authors: Kumar Vasantha H , Skrobacz Annie , Ma Changxing
Published: April 2024

Introduction:
Fetal hypoxia from intrapartum events can lead to absent heart rate (HR) or bradycardia (BC) at birth requiring neonatal resuscitation. Neonatal resuscitation guidelines do not differentiate infants with BC (HR<100/min) from absent HR at birth;

Hypothesis:
As HR is the primary determinant of resuscitation, we hypothesize that infants with no HR at 1min [determined by Apgar score (AS) of 0 @ 1min] would require more extensive resuscitation with worse clinical outcomes compared to infants with BC at 1min (determined by AS=1 @ 1 min).

Methods:
A retrospective analysis was done on infants born from 1/1/00 - 12/31/15 with AS of 0 (ASZ grp) or AS of 1 (ASN grp) at 1min. Patient demographics, resuscitation characteristics & clinical outcomes were analyzed in both the groups. Descriptive statistics & logistic procedure was performed (SAS System, Cary, NC).

Results:
Table.1 summarizes the resuscitation characteristics analyzed. AS were different between the groups over time (Fig.1). Death was higher in ASZ grp compared to ASN grp [0.37 (0.18-0.77)] & at lower gestational ages (GA) [0.82 (0.76-0.89)]. Infants who died had lower AS at 5 min [0.67 (0.55-0.82)]. Infants < 32 wks GA had higher incidence of PDA & severe IVH in the ASZ grp.

Conclusions:
Infants with no HR at 1min did worse than infants with BC. Death & low AS may reflect the severity of illness at birth, particularly in premature infants with no HR. Current guidelines do not address management of infants with HR of zero at birth. NRP need to include an algorithm for a subset of infants with absent HR at birth, as prompt resuscitation may decrease mortality & improve clinical outcomes of these infants.