bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotype-Genotype Correlations of GH1 Gene Variants in Patients with Isolated Growth Hormone Deficiency or Multiple Pituitary Hormone Deficiency
Authors: Öztürk Ayşe Pınar , Yavas Abali Zehra , Aslanger Ayça Dilruba , Bas Firdevs , Toksoy Güven , Karaman Volkan , Bagirova Gulandam , Poyrazoglu Sukran , Uyguner Zehra Oya , Darendeliler Feyza
Published: June 2023

Introduction: Genetic forms of growth hormone deficiency (GHD) may occur as isolated GHD (IGHD) or as a component of multiple pituitary hormone deficiency (MPHD). This study aimed to present the clinical and molecular characteristics of patients with IGHD/MPHD due to the GH1 gene variants. Methods: A gene panel accommodating 25 genes associated with MPHD and short stature was used to search for small sequence variants. Multiplex ligation-dependent probe amplification was performed in patients with normal panel results to investigate gross deletion/duplications. Segregation in the family was performed by Sanger sequencing. Results: The GH1 gene variants were detected in 5 patients from four unrelated families. One patient had IGHD IA due to homozygous whole GH1 gene deletion and one had IGHD IB due to novel homozygous c.162C>G/p.(Tyr54*) variant. Two patients from a family had previously reported heterozygous c.291+1G>A/p.(?) variant in which clinical and genetic characteristics were compatible with IGHD II accompanying MPHD. One patient had clinical and laboratory characteristics of IGHD II with MPHD but the heterozygous c.468 C>T/p.(R160W) variant had conflicting results about the relationship with the phenotype. Conclusion: Expanding our knowledge of the spectrum of GH1 gene variants by apprehending clinical and molecular data of more cases, helps to identify the genotype-phenotype correlation of IGHD/MPHD and the GH1 gene variants. These patients must be regularly followed up for the occurrence of additional pituitary hormone deficiencies.
Caries Experience in Elderly People Consuming a Milk-Based Drink Nutritional Supplement: A Cross-Sectional Study
Authors: Castro Ramiro J. , Gambetta-Tessini Karla , Clavijo Ignacio , Arthur Rodrigo A. , Maltz Marisa , Giacaman Rodrigo A.
Published: June 2023

Nutritional supplements have been recommended to cope with malnutrition in elderly persons. In Chile, the Supplementary Nutrition Program for the Elderly (PACAM, for its Spanish acronym) consists in a monthly distribution of a low-fat-milk-based drink that contains 8% sucrose. The aim of this study was to determine whether older persons consuming the milk-based drink have a higher caries experience when compared to those not receiving the supplement. A cross-sectional study was conducted in the Maule Region in Chile. The representative sample comprised two groups: (a) PACAM consumers (CS) (n = 60) and (b) nonconsumers (NCS) (n = 60). Participants received intraoral examination and coronal (DMFT/DMFS) and root caries (RCI index) experience were recorded. Additionally, questionnaires regarding acceptability and consumption habits of PACAM and a 24-h diet recall were applied. The influence of predictors was calculated using binary logistic regression for a dichotomized DMFS and Poisson Regression for root caries lesions. A p value <0.05 was considered significant. No differences were detected in food consumption patterns between study groups (p > 0.05). CS participants had increased dairy product consumption. Higher DMFS mean value was observed in the CS (85.35 ± 39.0) compared with NCS (77.28 ± 28.9) (p = 0.043). The multivariate analysis showed nonconsumers of the milk-based product (β = −0.41, p = 0.02) are less likely to have root surfaces affected by caries. Additionally, CS show higher RCI, compared to nonconsumers (β = −0.17, p = 0.02). Daily consumption of a PACAM’s milk-based drink supplement seems to increase coronal and root caries risk. Based on these results, composition modification of milk-based drinks with added sucrose appears mandatory.
Perdre l’appétit. Le refus de l’autre comme quête de soi. Exemples sahariens, japonais et français
Authors: Figueiredo Cristina
Published: June 2023

Cette réflexion anthropologique s’appuie sur une recherche menée auprès de jeunes garçons, de 13 à 25 ans, cloîtrés dans leur chambre. Leur immobilité, que ne justifie aucun handicap physique ou psychique, interroge la place du corps au moment du passage à l’âge adulte. Ces jeunes expriment une absence d’appétit de l’autre qui va de pair avec l’abstinence sexuelle que leur retrait oblige. L’hypothèse émise est qu’ils vivent un rapport au corps, à leur identité sexuelle - et à leur sexualité- ainsi qu’à l’alimentation, comparable aux jeunes filles souffrant d’anorexie mentale mais de manière inversée. Ces conduites interrogent les rapports de genre et la distribution des rôles au sein de la famille. À partir d’entretiens et d’observations, à domicile et dans des structures de soin, cet article montre que ces corps adolescents invisibilisés par l’enfermement ou l’extrême maigreur sont paradoxalement une expression ostentatoire d’une dépossession de soi. Un appétit nouveau est possible lorsque le désir de différenciation émerge et permet de nouvelles rencontres.
O lugar de enunciação de dois bebês com sofrimento psíquico e atraso de linguagem
Authors: Bolzan Renata Souto , Souza Ana Paula Ramos de
Published: June 2023

Este artigo analisa a singularidade linguística e psíquica de dois bebês com desfecho de linguagem distintos aos dois anos. Para análise utilizou-se a entrevista inicial e continuada, os Indicadores Clínicos de Referência/Risco ao Desenvolvimento Infantil (IRDI), os Sinais Enunciativos de Aquisição da Linguagem (SEAL), além de filmagens da interação entre mãe e bebê. Os resultados indicaram que apenas um dos casos houve superação do sofrimento psíquico e atraso na linguagem a partir do segundo ano de vida.  Tanto o exercício das funções parentais quanto as condições dos bebês são fatores importantes em sua constituição psíquica e linguística, o que traz reflexões interdisciplinares importantes acerca da singularidade na relação entre esses dois aspectos do desenvolvimento infantil.
CLIC4 Regulates Endothelial Barrier Control by Mediating PAR1 Signaling via RhoA
Authors: Kleinjan Matthew L. , Mao De Yu , Naiche L.A. , Joshi Jagdish Chandra , Gupta Ahana , Jesse Jordan J. , Shaye Daniel D. , Mehta Dolly , Kitajewski Jan
Published: June 2023

Background:

Endothelial CLICs (chloride intracellular channel proteins) CLIC1 and CLIC4 are required for the GPCRs (G-protein–coupled receptors) S1PR1 (sphingosine-1-phosphate receptor 1) and S1PR3 to activate the small GTPases Rac1 (Ras-related C3 botulinum toxin substrate 1) and RhoA (Ras homolog family member A). To determine whether CLIC1 and CLIC4 function in additional endothelial GPCR pathways, we evaluated CLIC function in thrombin signaling via the thrombin-regulated PAR1 (protease-activated receptor 1) and downstream effector RhoA.

Methods:

We assessed the ability of CLIC1 and CLIC4 to relocalize to cell membranes in response to thrombin in human umbilical vein endothelial cells (HUVEC). We examined CLIC1 and CLIC4 function in HUVEC by knocking down expression of each CLIC protein and compared thrombin-mediated RhoA or Rac1 activation, ERM (ezrin/radixin/moesin) phosphorylation, and endothelial barrier modulation in control and CLIC knockdown HUVEC. We generated a conditional murine allele of
Clic4
and examined PAR1-mediated lung microvascular permeability and retinal angiogenesis in mice with endothelial-specific loss of
Clic4
.

Results:

Thrombin promoted relocalization of CLIC4, but not CLIC1, to HUVEC membranes. Knockdown of CLIC4 in HUVEC reduced thrombin-mediated RhoA activation, ERM phosphorylation, and endothelial barrier disruption. Knockdown of CLIC1 did not reduce thrombin-mediated RhoA activity but prolonged the RhoA and endothelial barrier response to thrombin. Endothelial-specific deletion of
Clic4
in mice reduced lung edema and microvascular permeability induced by PAR1 activating peptide.

Conclusions:

CLIC4 is a critical effector of endothelial PAR1 signaling and is required to regulate RhoA-mediated endothelial barrier disruption in cultured endothelial cells and murine lung endothelium. CLIC1 was not critical for thrombin-mediated barrier disruption but contributed to the barrier recovery phase after thrombin treatment.
Abstract 01: Diagnostic Yield, Safety, and Outcomes with Head-to-Pelvis Sudden Death Computed Tomographic Imaging after Idiopathic Out-of-Hospital Cardiac Arrest: The CT First Cohort Study
Authors: Branch Kelley R , Gatewood Medley , Kudenchuk Peter , Maynard Charles , Sayre Michael R , Carlbom David , Edwards Rachael , Karatasakis Aris , Counts Catherine , Gunn Martin
Published: June 2023

Introduction:
In survivors of out-of-hospital cardiac arrest without an obvious cause (idiopathic OHCA), diagnosing OHCA causes and complications is challenging in early post-arrest care.

Hypothesis:
Head-to-pelvis sudden death computerized tomographic CT angiography (SDCT) <6 hours after successful resuscitation will improve the time and diagnostic ability to identify the etiology of OHCA and time-critical diagnoses compared to the standard of care (SOC) alone.

Methods:
CT FIRST was a prospective observational pre-/post-cohort study of patients successfully resuscitated from OHCA. Inclusion criteria included idiopathic OHCA, age>18 years, clinical stability to undergo SDCT, no known prior cardiomyopathy or obstructive coronary artery disease. SDCT, including ECG-gated thoracic CT, was introduced to the SOC for patients resuscitated from idiopathic OHCA (pre-cohort; years 11/2014-2/2017) and compared to SOC alone (post-cohort, years 1/2011-10/2014). CT scans could be clinically ordered as part of SOC. Primary endpoints were diagnostic SDCT diagnostic yield, time to identify OHCA and time-critical diagnoses, patient safety, and survival to hospital discharge.

Results:
Baseline characteristics between the SDCT (N=104) and the SOC (N=143) cohorts were similar. A CT scan (head, chest, and/or abdomen) was clinically ordered in 74 (52%) of SOC alone patients. The primary outcomes (Table) demonstrate that compared to SOC alone, SDCT increased the identification of OHCA causes and early diagnosis of time-critical etiologies without an increase in renal insufficiency. SDCT reduced the time to OHCA diagnosis by 78%. Total number of time-critical diagnoses and patient survival to discharge were unchanged between SOC alone and SDCT cohorts.

Conclusions:
SDCT scanning early after OHCA resuscitation safely improved the efficiency and diagnostic yield for causes of OHCA compared to the standard of care.
Abstract 10005: Pregnancy Complications Are Associated With Premature Coronary Artery Disease - Linking Three South Australian Cohorts
Authors: Khoja Adeel , Andraweera Prabha H , Tavella Rosanna , Gill Tiffany , Arstall Margaret A
Published: June 2023

Introduction:
There is increasing evidence that women who experience placenta-mediated pregnancy complications and gestational diabetes mellitus (GDM) are more likely to develop coronary artery disease (CAD) at a younger age. This is the first study to assess the relationship between pregnancy complications and premature coronary artery disease (PCAD) in Australian women.

Hypothesis:
We hypothesized that there is an association between placenta-mediated pregnancy complications, GDM and risk of CAD prior to 60 years of age.

Methods:
The research project involved a data linkage approach merging three databases of South Australian cohorts by employing a retrospective, age-matched case-control study design. Cases (n=721) were ascertained from Coronary Angiogram Database of South Australia (CADOSA). Women <60 years from CADOSA were linked to South Australian Perinatal Statistics Collection (SAPSC) to determine their pregnancy outcomes. Controls (n=194) were ascertained from North West Adelaide Health Study (NWAHS) and comprised of women who were healthy or had health conditions other than CAD, age-matched to CADOSA (+/- 5 years) and linked to SAPSC to determine their pregnancy outcomes. PCAD was defined as
>
50% stenosis in one or more coronary arteries at coronary angiography.

Results:
Women who were diagnosed with PCAD were more likely to have experienced a placenta-mediated pregnancy complication, previous miscarriage, asthma or anaemia and/or have risk factors for CAD including pre-existing diabetes (I & II), active smoking and obesity during pregnancy compared to women without a history of CAD as shown in the table below (p
<
0.05). GDM was not associated with PCAD in these cohorts.

Conclusion:
Women diagnosed with PCAD have conventional CVD risk factors and some that are uniquely related to their pregnancy. These clinical events may be considered novel risk factors for future PCAD and require attention in contemporary preventative cardiology practice.
Abstract 10014: Work-Related Stress and Ideal Cardiovascular Health: The Multi-Ethnic Study of Atherosclerosis
Authors: Ogunmoroti Oluseye , Osibogun Olatokunbo , Allen Norrina B , Okunrintemi Victor , Commodore-Mensah Yvonne , Blumenthal Roger S , Michos Erin D
Published: June 2023

Background:
Work-related stress is a psychosocial risk factor linked to a higher risk of adverse health outcomes, especially cardiovascular disease (CVD). However, the association between work-related stress and ideal cardiovascular health (CVH) is not well established. We examined whether work-related stress was negatively associated with favorable CVH in a multi-ethnic population of adults free of CVD at baseline.

Methods:
We analyzed cross-sectional data of 6,486 men and women aged 45-84 years. Work-related stress was assessed by the presence or absence of ongoing job difficulty and ongoing job difficulty for >6 months. CVH was measured by a scoring system that assigned points to 7 metrics (smoking, physical activity, body mass index, diet, total cholesterol, blood pressure and blood glucose). Each metric had 3 categories: poor (0 points), intermediate (1 point) and ideal (2 points). The total score attainable was 14 points, categorized as inadequate (0-8 points), average (9-10 points) and optimal (11-14 points). We used polytomous logistic regression to examine the association of work-related stress with the CVH score and number of ideal metrics, adjusted for sociodemographic factors.

Results:
The mean age (SD) was 62 (10) years and 53% were women. Ongoing job difficulty was reported by 14% of participants while 13% reported ongoing job difficulty for >6 months. Participants who reported ongoing job difficulty had 21% and 24% lower odds of having average and optimal CVH scores, respectively
(Table).
Additionally, the presence of ongoing job difficulty for >6 months was associated with 23% and 24% lower odds of having average and optimal CVH scores, respectively. A similar trend was observed for the association of work-related stress with the number of ideal metrics.

Conclusion:
Work-related stress was negatively associated with favorable CVH. Stress reduction and CVH promotion programs in the workplace may decrease the incidence of CVD.
Abstract 10034: Novel Late-Gadolinium Enhanced Cardiac Magnetic Resonance (LGE-CMR)-Based Computational Heart Paradigm Predicts Optimal Ventricular Tachycardia (VT) Ablation Targets in Arrhythmogenic Right Ventricular (RV) Cardiomyopathy (ARVC)
Authors: Zhang Yingnan , Prakosa Adityo , Sung Eric , Gasperetti Alessio , Carrick Richard , James Cynthia , Zimmerman Stefan , Tichnell Crystal , Murray Brittney , Calkins Hugh G , Tandri Harikrishna S , Trayanova Natalia
Published: June 2023

Introduction:
ARVC is an inherited cardiac disease that increases risk of life-threatening VTs in young adults. Catheter ablation, a mainstay of VT treatment in ARVC, remains challenging due to difficulties in identifying optimal VT ablation targets.

Hypothesis:
Right Ventricular Cardiomyopathy Ablation Targeting (RVCAT) is a novel digital-heart paradigm that accurately predicts the optimal VT ablation targets of ARVC patients.

Methods:
We retrospectively enrolled 11 ARVC patients; 8 presented with clinical VTs and underwent VT ablation. In all patients, RV hyperenhancement on LGE-CMR was identified. For this study, we developed RVCAT, the first computational heart model integrating RV personalized diffuse and dense fibrosis as VT substrates. Each region was assigned ARVC-specific electrophysiologic properties. VT inducibility was assessed via rapid pacing in each model. If inducible, optimal ablation targets, which rendered the RV substrate non-inducible for each VT, were determined. Targets were compared to electroanatomic voltage maps (EAM), locations of clinical ablations, and clinical records.

Results:
Personalized model predictions correlated well with clinical observations. All 8 models of the patients with a history of clinical VT had inducible VTs (Fig A). Furthermore, model VT circuit locations matched the clinical description. Substrate distribution in models matched low-voltage zones in EAM. The predicted ablation targets coincided with clinical ablations (Fig B). Results showed that the volume of model ablation lesions was significantly smaller than that of clinical ablations (1.02±0.68 versus 1.45±0.91, p<0.05, Fig C). For the 3 patients who did not have VTs, their corresponding heart models correctly predicted that no VTs would be induced.

Conclusions:
RVCAT is a novel digital-heart technology for optimal ARVC VT ablation guidance that can be potentially integrated into clinical workflows for augmenting therapeutic precision.
Abstract 10039: Cardiomyocyte N-myristoylation Plays an Essential Role During the Development of Heart Failure
Authors: Tomita Yusuke , Misaka Tomofumi , Anzai Fumiya , Ichimura Shohei , Wada Kento , Kimishima Yusuke , Takeishi Yasuchika
Published: June 2023

Background:
N-myristoylation is co- and post-translational modifications of proteins, which involve attachment of myristic acid to the N-terminal glycine. Although N-myristoylation plays important roles in physiological activities such as intracellular signaling, the precise regulation and functional relevance of N-myristoylation in the heart remain to be elucidated.

Methods and Results:
We applied a click chemistry-based approach to determine the global N-myristoylated protein profiling in the cardiomyocyte. Proteomics analysis identified 41 and 34 N-myristoylated proteins in H9c2 myocytes and neonatal rat cardiomyocytes, and 66.1% of them were discovered for the first time at endogenous levels. The levels of N-myristoylation were significantly decreased by the N-myristoyltransferase (NMT) 2 inhibition with siRNA or adenoviral shRNA knockdown, but not by the NMT1 inhibition. In response to angiotensin II (AII), N-myristoylated levels were differentially altered, and MARCKS was identified as the most down-regulated N-myristoylated protein. Wild-type MARCKS was localized to the cellular membrane, while the mutant MARKS with replacement of N-terminal glycine to alanine (G2A), which lacked the capacity of N-myristoylation, exhibited cytosolic distribution. Cardiomyocyte hypertrophy was exacerbated in mutant G2A MARCKS accompanied by increased levels of histone acetylation and phosphorylation of HDAC4 and CaMKII after AII. Gene transfer delivering NMT2 gene specific to the heart using adeno-associated virus 9 significantly improved pressure overload-induced left ventricular systolic dysfunction, cardiac hypertrophy, and myocardial fibrosis, associated with decreased levels of histone acetylation after the transverse aortic constriction in mice (
Fig
).

Conclusion:
Cardiomyocyte N-myristoylation plays an essential role in developing heart failure, and its modification by NMT2 may be a novel therapeutic strategy for heart failure.
Abstract 10050: Omecamtiv Mecarbil and Its Effects on Cardiac Parameters in Heart Failure With Reduced Ejection Fraction (HFrEF). A Meta-Analysis of Randomized Controlled Trials
Authors: Farooqui Arafat , Bilal Haris , Saleem Naira , Uddin Syed Mohammad Mazhar , Maheshwari Sanjay , SHETTY VIJAY , Hollander Gerald , Shani Jacob
Published: June 2023

Introduction:
Omecamtiv mecarbil (OM) is a novel selective cardiac myosin activator that has been shown to improve cardiac function in patients with HFrEF. Proposed mechanism of action suggests that it increases myocardial systolic function and systolic ejection time without associated increases in intracellular concentrations of calcium or the rate of change in left ventricular pressure or any direct effects on vascular tissue, cardiovascular receptors, or ion channels.

Methods:
Systematic review identified phase II/III randomized controlled trials (RCTs) evaluating OM versus placebo. Mean Difference (MD) of different echocardiographic parameters from baseline and Odds Ratios (OR) of cardiovascular (CV) death (along with 95% confidence intervals; CI) were extracted to compute pooled MD and OR using RevMan v.5.3. Random effects model was employed when there was significant heterogeneity (>40%, as assessed by I-squared).

Results:
Four RCTs were finalized (n=9331; OM: 4722, placebo: 4609). Majority of the patients were males (n=7359; 79%), of white ethnicity (n=7345; 78.7%), and had ischemic heart failure (n=5109; 54.7%). All patients had EF <40% and were on guideline-directed therapy. When patients were pooled for stroke volume; OM increased mean SV to 4.34 ml from baseline as compared to placebo (MD 4.34, 95% CI 2.03-6.65; p=0.0002; I
2
=0%). Mean LV ejection time increased to 32 milliseconds (ms) (MD 32.60, 27.34-37.87; p<0.00001; I
2
=84%). OM resulted in 1.68 mm reduction in mean LV end-systolic diameter (MD -1.68; -2.73 to -0.62; p=0.002; I
2
=0%)). However, reduction in mean end-diastolic diameter (MD -1.05; -1.98 to -0.12; p=0.34; I
2
=42%) was statistically non-significant. Mean LV Fractional Shortening improved to 2% with OM but was statistically insignificant (MD 2.18; 0.54-3.82; p=0.09; I
2
=42%). OM resulted in slightly decreased heart rate (MD -1.77 beats/min; -2.29 to -1.24; p<0.00001; I
2
=0%) with no effect on mean systolic BP (MD -0.05; -0.73 to 0.64; p=0.89; I
2
=0%). In terms of CV mortality, OM decreased the odds for mortality but results were statistically non-significant (OR 0.93, 95% CI 0.80 to 1.08; p=0.34; I
2
= 0%).

Conclusion:
Omecamtiv mecarbil improved the echocardiographic parameters in patients with HFrEF.
Abstract 10057: Cerebral Palsy Patients Admitted for Acute Myocardial Infarction; Insights From the 2019 National Inpatient Sample
Authors: Ramphul Kamleshun , Verma Renuka , Kumar Nomesh , Ramphul Yogeshwaree , Kumari Komal , Lohana Petras , Sombans Shaheen , Arti Fnu , Mejias Stephanie G
Published: June 2023

Introduction:
Past studies have suggested that respiratory diseases are the most common cause of death among children with cerebral palsy (CP). At the same time, cardiovascular complications and cancer could be the leading killer among adult in those patients. The outcomes of cerebral palsy patients and risk factors following an episode of Acute Myocardial Infarction (AMI) have not been widely examined.

Methods:
A retrospective study via the 2019 National Inpatient Sample was conducted. Cases with CP diagnosis were retrieved via their appropriate ICD-10 codes (G80.0x). We also filtered to include patients with a principal diagnosis of AMI. Various categorical variables were compared via Chi-Square tests.

Results:
In 2019, 295 patients with cerebral palsy were admitted with AMI. CP patients were younger (mean age 63.20 vs. 66.93 years) and more common among Whites (86.0%), covered by Medicare (79.7%), and of ages >60 (66.1%). Compared to non-CP patients, CP patients also recorded more cases with depression (20.3% vs. 9.3%) and drug abuse (8.5% vs. 3.0%). However, they had less cases with smoking (28.8% vs. 49.3), obesity (13.6% vs. 21.0%), hyperlipidemia (59.3% vs. 68.6%), old myocardial infarct (8.5% vs. 16.6%), hypertension (78.0% vs. 82.8%), diabetes (35.6% vs. 41.2%), peripheral vascular disease (6.8% vs. 10.6%), acute kidney injury (10.2 % vs. 20.8%), ventricular tachycardia (6.8% vs. 7.2%), and paroxysmal atrial fibrillation (6.8% vs. 9.9%). Only 38.6% of CP patients underwent PCI.

Conclusions:
CP patients may present with AMI at a younger age and express a higher depression and drug abuse rate. Physicians and providers linked with their care should be encouraged to reach out to them for signs of depression and provide them with adequate facilities to seek treatment.
Abstract 10064: Tracking Multi-Organ Treatment Response in Systemic Al-Amyloidosis With Cardiac Magnetic Resonance Derived Extracellular Volume Mapping
Authors: Ioannou Adam , Patel Rishi , Razvi Yousuf , Porcari Aldostefano , Hutt David , Martinez-Naharro Ana , Kotecha Tushar , Venneri Lucia , Chacko Liza , Knight Daniel , Lachmann Helen
Published: June 2023

Introduction:
Systemic light-chain (AL) amyloidosis commonly involves the liver, spleen and heart. Cardiac magnetic resonance (CMR) with extracellular volume (ECV) mapping has demonstrated accuracy in measuring hepatic, splenic and cardiac amyloid infiltration. We sought to assess multi-organ response to treatment using CMR derived ECV mapping.

Methods:
We identified 351 patients who underwent baseline SAP scintigraphy and CMR at diagnosis, of which 171 had follow-up imaging.

Results:
Liver and spleen ECV correlated with amyloid load assessed by SAP scintigraphy (R=0.751, P<0.001; R=0.765, P<0.001), with serial measurements accurately tracking treatment response. ECV regression was observed at 6-months in those with a good haematological response (liver=15%, spleen=15%, heart=5%). The remaining patients with a good response had stable liver and spleen ECVs, but 20% had cardiac progression. Baseline liver (HR=1.03, 95%CI[1.01-1.05], P<0.001) and myocardial ECV (HR=1.05, 95CI%[1.03-1.07], P<0.001) independently predict mortality. Change in liver (HR=1.06,95%CI[1.01-1.11], P=0.015) and myocardial ECV (HR=1.11, 95%CI[1.02-1.19], P=0.011) a 6-months independently predict mortality, while liver and cardiac regression at 12-months predict survival.

Conclusions:
Multi-organ ECV quantification accurately tracks treatment response, and demonstrates different rates of organ regression, with the liver and spleen regressing more rapidly than the heart. Liver and myocardial ECV at diagnosis and increases in ECV at 6-months independently predict mortality.
Abstract 10093: Association Between B-Thalassemia and Atrial Fibrillation: Insights From the United States National Inpatient Sample
Authors: Abdelmottaleb Wael , Maraey Ahmed , Ozbay Mustafa , Elsharnoby Hadeer , Khalil Mahmoud
Published: June 2023

Introduction:
β-thalassemia (BT) disease requires a lifelong blood transfusion. Despite improved prognosis with transfusion and chelation therapy, the iron overload can predispose to atrial fibrillation (AF). We sought to study the impact of AF on BT patients through large database analysis.

Methods:
The study used the Agency for Healthcare Research and Quality’s Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS) for 2016-2019. Adult BT admissions were included. BT admissions were identified using ICD-10 code (D56.1). Admissions were stratified according to AF presence. A series of multivariate logistic regression was performed to evaluate the impact of atrial fibrillation on BT and to account for potential confounders. Continuous variables were compared using Student t-test, and categorical variables were compared using ꭓ2 tests. Subgroup analysis according to sex was performed. Outcomes evaluated were in-hospital mortality and prolonged length of stay (LOS) ≥ 75th percentile.

Results:
A total of 17,150 admissions were included, of which 2,100 (12.2%) had an associated diagnosis of AF. Admissions with AF were older (72.1 vs 47.3, P<0.001), white race (66% vs 41%), and more likely to have congestive heart failure (CHF), hypertension, valvular heart disease, and renal disease. BT was associated with higher AF prevalence than non-BT admissions across all age groups. AF was not associated with increased risk of in-hospital mortality in the general cohort nor increased LOS (adjusted odds ratio [aOR]: 1.36 [0.67-2.78], P=0.398, and 1.00 [0.78-1.29], P=0.997, respectively). In subgroup analysis, including only female admissions, AF was associated with increased in-hospital mortality (aOR: 2.73 [1.09-6.8], P=0.031) but not with prolonged LOS (P=0.218). Predictors of in-hospital mortality were age, CHF, and liver disease, while predictors of prolonged LOS were Diabetes Mellitus in addition to CHF and age.

Conclusions:
We reported significant findings. First, AF is more common in BT compared to the general population, irrespective of age. Second, AF was independently associated with increased mortality in BT females. Third, CHF, liver disease, diabetes, and increased age are poor outcome predictors.
Abstract 10097: Clinical Presentations and Outcomes of Atherosclerotic Cardiovascular Disease With and Without Underlying Clonal Hematopoiesis
Authors: Gumuser Esra , Sporn Zachary A , Paruchuri Kaavya , Uddin Md Mesbah , Niroula Abhishek , Ebert Benjamin , Natarajan Pradeep , Honigberg Michael
Published: June 2023

Introduction:
Clonal hematopoiesis of indeterminate potential (CHIP), the expansion of hematopoietic stem cells harboring a leukemogenic mutation without blood cancer, is associated with accelerated atherosclerosis in large datasets. The clinical impact of underlying CHIP mutations on clinical presentation and outcomes among those with atherosclerotic cardiovascular disease (ASCVD) events is unknown.

Methods:
We included patients in the Mass General Brigham Biobank with available whole exome sequences who experienced a first ASCVD event (coronary artery disease [CAD], cerebrovascular, or peripheral artery event) following or within 6 months before blood sample collection. Individuals with CHIP (variant allele fraction >2%) were matched 1:2 with CHIP-free patients by qualifying ASCVD subtype, age, sex, race, current/former smoking, and type 2 diabetes. Clinical characteristics, management, and subsequent outcomes were abstracted by chart review.

Results:
The sample (N=120) included 40 individuals with and 80 without CHIP (overall mean age 64.1 years), of whom 99 (82.5%) had CAD as the qualifying event. The most common CHIP drivers were DNMT3A (32.5%), TET2 (30.0%), and PPM1D (15.0%). Median (IQR) calculated 10-year ASCVD risk was 13.4% (6.9-19.5%) in those with CHIP vs. 15.5% (9.6-22.7%) in those without. Among individuals with CAD, burden of obstructed major coronary arteries on angiography was unexpectedly lower in those with CHIP (P=0.04), as were rates of revascularization. Over a median 4.1 years of follow-up after the index event, the composite of acute coronary syndrome, stroke, peripheral artery disease, and mortality occurred in 35.0% with CHIP vs. 25.0% without (P=0.29), including in 50.0% with PPM1D, 33.3% with TET2, and 23.1% with DNMT3A CHIP.

Conclusions:
CHIP may be prognostic among those with ASCVD events. Future larger studies should characterize mechanisms of first and recurrent events and heterogeneity across CHIP subtypes.
Abstract 10112: Association of Coronary Artery Disease Testing During Index Hospitalization for New-Onset Heart Failure With Thirty-Day Readmission Rates and Mortality
Authors: Jang Sun-Joo , Malaguez Webber Fabricio , Yeo Ilhwan , Pinto Edward R , Da Silva De Abreu Adrian , Kittleson Michelle M , Zarich Stuart
Published: June 2023

Introduction:
Testing for coronary artery disease (CAD) is recommended for patients with new-onset heart failure (HF). There are limited data on the association between testing for CAD during index hospitalization for patients with the new-onset HF and early readmission rates and readmission mortality.

Hypothesis:
CAD testing for new-onset HF during index hospitalization may reduce 30-day readmission rates and readmission-related mortality.

Methods:
Patients hospitalized for new-onset HF were identified from the Nationwide Readmission Database of the United States. Clinical characteristics, 30-day readmission rates, readmission-related mortality were compared in patients with or without testing for CAD during index hospitalization. CAD testing includes coronary angiography, coronary CT angiography, cardiac MRI, nuclear imaging or cardiac stress test.

Results:
Between January 2016 and November 2019, of 151,172 patients hospitalized for new-onset HF, 30,444 (20.1%) patients underwent testing for CAD during index hospitalization. Younger patients, males, and patients with HF with reduced ejection fraction (HFrEF) had more frequent testing for CAD. Only 9.5% of CAD-tested patients received percutaneous coronary intervention during the index hospitalization. Patients with CAD testing had lower 30-day readmission rates than those without testing (11.4% vs 14.3%, P<0.001; adjusted odds ratio (OR) 0.81, 95% confidence interval (CI) 0.76 to 0.87). Patients with CAD testing had lower 30-day readmission-related mortality rates than those without testing (0.5% vs 0.9%, P<0.001; adjusted OR 0.82, 95% CI 0.65 to 1.04). Readmission rate for HF at 30 days was 2.3% for patients with CAD testing vs 3.5% for those without testing (P<0.001; adjusted OR 0.67, 95% CI 0.59 to 0.76). There was a significant interaction between HF type (HFrEF vs HF with preserved EF) and CAD testing on 30-day readmission rates (P for interaction <0.001).

Conclusions:
Testing for CAD during index hospitalization for patients with new-onset HF was associated with reduced 30-day readmission rates. There was substantial decrease in readmission for HF and readmission-related mortality in patients who underwent CAD testing during index hospitalization.
Abstract 10153: Cord Blood Metabolite Signatures for Elevated Blood Pressure in Childhood and Adolescence
Authors: Zhang Mingyu , Brady Tammy M , Buckley Jessie P , Appel Lawrence J , Hong Xiumei , Wang Guoying , Liang Liming , Wang Xiaobin , Mueller Noel T
Published: June 2023

Background:
Risk factors for high blood pressure (BP) in children start
in utero
. Cord blood metabolites reflect exposures of the developing fetus to the
in utero
environment. No studies have examined whether cord blood metabolites are associated with BP in children.

Objectives:
To examine prospective associations of cord blood metabolites with systolic BP (SBP), diastolic BP (DBP), and risk of elevated BP in childhood and adolescence.

Methods:
We used data from the Boston Birth Cohort. Metabolites were measured in cord blood plasma samples collected at birth. SBP and DBP were measured at clinic visits between 3 to 18 years. We calculated BP percentiles per the 2017 American Academy of Pediatrics Clinical Practice Guideline. We examined associations of cord metabolites with SBP and DBP percentiles using linear mixed models and with elevated BP using mixed-effects Poisson regression. We used the False Discovery Rate (FDR) method to adjust for multiple comparisons.

Results:
Our study included 902 mother-child dyads (60% Black, 23% Hispanic, 45% female). Children were followed for a median of 9.2 (IQR: 6.7-11.7) years, and the median number of BP observations per child was 7 (IQR: 4-11). After FDR adjustment, 3, 94, and 22 metabolites were respectively associated with SBP, DBP, and risk of elevated BP; 2 metabolites (1-methylnicotinamide, dimethylguanidino valeric acid) were associated with all three outcomes, and 22 metabolites were associated with both DBP and risk of elevated BP. After multivariable adjustment, 48 metabolites remained significantly associated with DBP. Metabolites that showed the strongest associations with SBP, DBP, and risk of elevated BP included nucleotides (e.g., xanthosine, hypoxanthine, xanthine) and acylcarnitines (e.g., C6 and C7 carnitines), which represent fatty acid oxidation and purine metabolism pathways.

Conclusions:
In this predominantly urban, low-income, minority cohort, cord blood metabolites were prospectively associated with BP and risk of elevated BP from childhood to adolescence. Acylcarnitines and purine metabolism may be involved in the early life origins of hypertension. Cord metabolites may explain the intergenerational effects of
in utero
environments on BP in childhood and adolescence.
Abstract 10170: Comparison of Impella, Intra-Aortic Balloon Pump, and Vasopressors Alone in Patients With Acute Myocardial Infarction and Cardiogenic Shock Undergoing Percutaneous Coronary Intervention
Authors: Javaid Awad I , Michalek Joel E , Aslam Imran , Gruslova Aleksandra B , Hoskins Serene A , Ahsan Chowdhury H , Feldman Marc D
Published: June 2023

Introduction:
Previous studies have compared Impella to intra-aortic balloon pump (IABP) in patients with acute myocardial infarction and cardiogenic shock (AMI-CS) undergoing percutaneous coronary intervention (PCI) but did not include a cohort of patients receiving vasopressors alone. We assessed the hypothesis that there would be a difference in clinical outcomes in patients with AMI-CS undergoing PCI who received Impella alone, IABP alone, and vasopressor therapy without MCS.

Methods:
We queried the National Inpatient Sample inclusive of 2015 to 2018 and created three propensity-matched cohorts (Impella alone vs IABP alone, Impella alone vs vasopressors without MCS, and IABP alone vs vasopressors without MCS). We performed propensity matching by adjusting for 21 clinical variables including age, comorbidities, and presence of lactic acidosis. Patients receiving both MCS and vasopressors were excluded, in order to best isolate the effect of each intervention.

Results:
Among 17,762 hospitalized patients with AMI-CS undergoing PCI, Impella use was associated with significantly higher in-hospital mortality (40.6% vs 27.4%; p=0.003), major bleeding (29.3% vs 13.5%; p < 0.001), acute kidney injury (56.4% vs 45.9%; p=0.04), and hospital charges compared to IABP use (p <0.001) (Figure). Impella patients had significantly higher rates of mortality (42.8% vs 35.5%; p=0.01) and major bleeding (32.7% vs 22.5%; p=0.001), when compared to patients with vasopressors without MCS. There were no significant differences in clinical outcomes between IABP patients and patients receiving vasopressors without MCS.

Conclusions:
When compared to IABP or vasopressor therapy without MCS, Impella patients with AMI-CS undergoing PCI had higher mortality, major bleeding, and in-hospital costs. A vasopressor-only strategy showed no difference in clinical outcomes when compared to IABP. Randomized trials are necessary to determine optimal MCS management in AMI-CS.
Abstract 10174: Intravenous Muse Cell Transplantation Enhances Angiogenesis and Reduces Muscle Fibrosis in a Mouse Hindlimb Ischemia Model
Authors: Hori Yusuke , Kitani Tomoya , Yanishi Kenji , SUGA TAKAOMI , Kusaba Tetsuro , Kushida Yoshihiro , Dezawa Mari , Matoba Satoaki
Published: June 2023

Introduction:
Multilineage-differentiating stress enduring (Muse) cells, a unique subpopulation of mesenchymal stem cells (MSCs), have been proposed as a promising cell source for regenerative medicine. However, the therapeutic potential of the Muse cells in ischemic limb disease remains unclear. In this study, we aimed to investigate therapeutic potential of Muse cell transplantation for the treatment of severe limb ischemia.

Methods and Results:
Muse cells isolated from human MSCs, non-Muse MSCs, or mouse bone marrow-derived mononuclear cells (BM-MNCs) were administered intravenously or intramuscularly to a mouse model of hindlimb ischemia (HLI). When the same number of cells were administered, blood flow recovery of the ischemic limb was significantly enhanced in the mice administered with Muse cells over 2 weeks compared to the others. Intravenous Muse cell administration resulted in comparable blood flow recovery to intramuscular Muse cell administration. Immunohistochemistry analysis revealed that intravenous Muse cell administration increased microvascular density and ameliorated interstitial fibrosis in the ischemic limb. We detected mCherry-labeled Muse cells expressing CD31 and human genomic DNA in the ischemic limb 1 week after the intravenous Muse cell administration. Muse cells produced higher VEGF compared to non-Muse MSCs, and Muse cell administration increased tissue VEGF level and expression of angiogenesis-related genes in the ischemic limb. Moreover, we found that Muse cell administration increased M2 macrophage and gene expression ratio of anti-inflammatory genes to proinflammatory gene, iNOS, in the ischemic limb. Lastly, we administered Muse cell intravenously at day 1 and 3, or high-dose BM-MNCs intramuscularly at day1 after the HLI surgery and found that repetitive Muse cell administration resulted in significantly enhanced blood flow recovery in the ischemic limb compared to high-dose BM-MNCs administration.

Conclusions:
Using an animal model, we demonstrated that intravenous Muse cell transplantation exerts robust therapeutic effects on limb ischemia injury. Therefore, Muse cell-based therapy may provide a novel therapeutic approach for patients with severe limb ischemia.
Abstract 10178: Concurrent Left Ventricular and Left Anterior Coronary Artery Thrombus;
Is Covid-19 an Innocent Bystander?
Authors: Somma Vincenzo , Brennan Anthony , Ha Francis J , Trytell Adam , Phan Khoa , Moneghetti Kegan J
Published: June 2023

Case presentation:
A 36-year-old male was admitted to a local hospital with respiratory failure secondary to COVID-19 pneumonia. Initial management included oxygen, dexamethasone and baricitinib. On day 14 of illness the patient developed severe chest pain associated with widespread dynamic ST segment elevation and an elevated high sensitivity troponin I (17516 ng/L). He was transferred to a tertiary center for cardiac evaluation. Cardiovascular risk factors included treated hypertension and obesity (BMI 34). Physical exam revealed a blood pressure of 145/95 mmHg, regular heart rate at 90 bpm and coarse crepitations in bilateral lower lungs with a 3L oxygen requirement. Differentials included myopericarditis however, clinical suspicion for an acute coronary syndrome remained high. Urgent coronary angiogram revealed a large filling defect (figure 1A) at the mid-vessel of the LAD at the 1st diagonal bifurcation, likely a thrombus. Dual antiplatelet therapy, heparin and tirofiban infusion were commenced. Furthermore, echocardiography performed the same day revealed a reduced LVEF secondary to LAD territory hypokinesis and an associated apical left ventricular thrombus measuring 2.2x1.3 cm (figure 1B). Once established on anticoagulation the patient experienced no further chest pain and was discharged home on warfarin.The left ventricular thrombus was monitored for resolution in the community with serial transthoracic echocardiograms.

Discussion:
Raised highly sensitive troponin in the vicinity of severe COVID-19 infection is common, however, when associated with chest pain and or dynamic ECG changes myocarditis must be considered. The cytokine storm triggered by a SARS-CoV-2 infection can be thrombogenic, resulting from increased platelet activation and decreased fibrinolysis. This process may further complicate the evaluation and acute coronary syndrome does need consideration, even in those patients at a younger age with minimal risk factors.
Abstract 10222: Impact of Bleeding Event for New Cancer Diagnosis in Patients With Antiplatelet Therapy After Percutaneous Coronary Intervention
Authors: Sakuma Yuya , Shimizu Takeshi , Kurosawa Yuta , Ohara Himika , Sugawara Yukiko , Muto Yuki , Sato Yu , Kiko Takatoyo , Sato Akihiko , Misaka Tomofumi , Yoshihisa Akiomi , Yamaki Takayoshi , Nakazato Kazuhiko , Ishida Takafumi , Takeishi Yasuchika
Published: June 2023

Background:
It has been reported that the bleeding event represents unmasking of an occult cancer in anticoagulated patients with atrial fibrillation. However, the impact of bleeding event in patients with antiplatelet therapy after percutaneous coronary intervention (PCI) for new cancer diagnosis remains unclear.

Methods and Results:
Consecutive 1796 patients with coronary artery disease who underwent PCI and taking antiplatelet therapy were enrolled. Patients taking oral anticoagulants were excluded, and relationships between bleeding event and new cancer diagnosis were examined. Among 1565 patients, 189 (12.0%) experienced any bleeding events defined as Bleeding Academic Research Consortium (BARC) type-2/3/5 bleeding, 78 (4.9%) experienced minor bleeding events defined as BARC type-2 bleeding, and 116 (7.4%) were diagnosed with new cancer during a mean follow-up period of 1528 days. Patients with any bleeding were older (71.3 vs. 68.8 years, P = 0.005) and had higher prevalence of being at Academic Research Consortium criteria for high bleeding risk (62.4% vs. 43.8%, P < 0.001) than those without bleeding event. Of 189 patients with any bleeding and 78 patients with minor bleeding events, 31 (16.4%) and 16 (20.5%) were diagnosed with new cancer, respectively. In the univariate Cox proportional hazard analysis, the incidence of new cancer diagnosis was higher in patients with any bleeding and minor bleeding events than those without bleeding event (hazard ratio [HR] 3.19, P < 0.001 and HR 5.70, P < 0.001, respectively). In the multivariate analysis after adjusting for confounding factors, any bleeding and minor bleeding events were the independent predictors of new cancer diagnosis (HR 2.27, P = 0.003 and HR 3.93, P < 0.001, respectively). In addition, any gastrointestinal bleeding and minor bleeding events were associated with higher rates of new gastrointestinal cancer diagnosis (HR 4.46, P = 0.041 and HR 6.73, P = 0.009, respectively).

Conclusion:
In patients with antiplatelet therapy after PCI, any bleeding and minor bleeding events were associated with subsequent new cancer diagnosis. Even minor bleeding should be taken care as the first manifestation of underlying cancer during antiplatelet therapy.
Abstract 10230: Epidemiology of Early and Late Ventricular Assist Device Infections in Bridge-to-Transplant Patients: A Single Centre Experience
Authors: Goyal Ansh , Hockney Sara M , Kumar Rebecca , Harap Rebecca , Wilcox Jane E , Pham Duc Thinh T , Stosor Valentina
Published: June 2023

Introduction:
Bacterial infections are common after ventricular assist device (VAD) implantation. Better understanding of their epidemiology in bridge-to-transplant (BTT) pts will allow for improved infection prevention, management, and optimization for transplantation.

Methods:
We performed a retrospective cohort study of 42 BTT pts with VAD infections from 4/2006-10/2020. VAD-specific and VAD-related infections were characterized according to 2011 ISHLT definitions. Infections were classified as early if occurring
≤
90 days, and late if occurring >90 days after VAD implantation.

Results:
The prevalence of VAD infections among BTT pts was 23%, with 24% of those occurring early and 76% occurring late. Pts with infections were predominantly male (n=32, 76%) and white (n=30, 71%), with non-ischemic cardiomyopathy (n=22, 52%), and mean age at implantation of 52.7y. There were no significant differences in baseline characteristics between pts who developed early or late VAD infections (Table 1). Pts had VAD infections involving the bloodstream (n=22), driveline (n=22), pump (n=9), and pocket (n=3), with an additional 10 pts with possible endocarditis and 3 with sternal infections/mediastinitis. Most superficial driveline infections occurred more than 90 days after implantation (19 vs. 1, p=0.029). There were no significant differences in the incidence of early and late infection for the remainder of VAD-related infections reviewed (Table 2). Gram-negative organisms were responsible for the most infections (n=15), followed closely by
Staphylococcus aureus
(n=14); there was no significant difference in organisms causing early vs. late infection (Table 3).

Conclusions:
In this single center study of BTT pts over a 14-year period, superficial drive-line infections rarely occurred in the first 90 days post-VAD implantation. Gram-negative rods and
Staphylococcus aureus
were nearly equally responsible for most infections.