bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10665: The Glycemic and Insulin Levels Contribute to the Sympathetic Response to Exercise in Individuals With and Without Diabetes Mellitus
Authors: Hamaoka Takuto , Leuenberger Urs A , Blaha Cheryl , Luck Jonathan C , Cui Jian
Published: June 2023

Introduction:
Exaggerated responses in blood pressure (BP) and muscle sympathetic nerve activity (MSNA) during exercise are suggested to contribute to adverse cardiovascular events. The risk of developing cardiovascular disease is elevated in patients suffering from diabetes mellitus (DM) and pre-DM; however, the relationship between the sympathetic responses to exercise and the glycemic and insulin indices in DM and non-DM remain unclear.Hypothesis: We hypothesized that the magnitude of MSNA response to exercise is related with glycemic and insulin indices in DM and Pre-DM subjects.

Method:
Eleven clinically diagnosed T2DM patients (54.0 ± 2.7 yrs) and 20 non-DM subjects (58.6 ± 2.3 yrs, 10 pre-DM [5.7%
≤
HbA1c < 6.5%] and 10 healthy subjects) were examined. All non-DM subjects, including pre-DM subjects, had no noted diseases and were not on any medication. Five DM patients were on antihypertensive agents. The BP and glycemic control in the DM patients was relatively well managed with medications (HbA1c, 6.8 ± 0.3 %) and were without other cardiovascular complications. Beat-by-beat BP, heart rate, and MSNA were recorded simultaneously under a resting condition and during static handgrip exercise (HGe) at 30% maximal voluntary contraction until fatigue.

Results:
Resting MSNA in DM was lower than non-DM subjects (P < 0.05). However, the MSNA response (i.e., the change) to HGe in DM was higher than non-DM (139% vs 75% increase, P < 0.05). The MSNA response to HGe was significantly correlated (R = 0.59, P < 0.05) with fasting blood glucose (FBG) across all subjects. Even in only pre-DM subjects, the MSNA response to HGe was significantly correlated with glucose/insulin indices (vs. FBG, R = 0.91, P < 0.05; vs. blood insulin concentration, R = 0.84, P < 0.05).

Conclusion:
In the present study, the MSNA response to exercise in T2DM patients was greater than that in non-DM subjects. Importantly, the MSNA response to exercise was correlated with glycemic/insulin indices over a broad range. This relationship was observed even before the development of DM. We speculate that the altered glycemic/insulin levels may contribute to the exaggerated sympathetic response to stress and in turn, contribute to the higher risk of cardiovascular diseases in these individuals.
Abstract 10730: Pkm2 Ablation Dysregulates Cardiac Glucose Metabolism in Mice
Authors: Lee Katie C , Williams Allison L , Shohet Ralph V
Published: June 2023

Introduction:
The predominant isoform of pyruvate kinase (PKM1) directs pyruvate to the Krebs cycle for oxidative metabolism in the healthy heart. Our lab described a hypoxia-mediated switch to the alternatively spliced isoform PKM2. The lower PKM activity of dimerized PKM2 redirects glycolytic metabolites to the pentose phosphate pathway (PPP) and lactate production. Recently, we have found that mice with deletion of Pkm2 had profound depletion of cardiac basal glucose and higher ROS levels compared to controls.

Hypothesis:
We hypothesize that glucose metabolism is dysregulated in the absence of Pkm2, where the remaining isoform PKM1 promotes oxidative metabolism, leading to accumulation of ROS.

Methods:
Global Pkm2 KO mice were used for this study. Transcript abundance was determined by RNA-seq and RT-qPCR. Cardiomyocytes were isolated according to an established Langendorff-free method, and metabolites were traced using [U-
13
C] glucose with LC/MS (n=3). ROS concentration was measured using DCFDA in cardiomyocytes incubated at 1% O
2
(n=4). Inflammatory marker C-reactive protein (CRP) was measured in plasma of mice before and after myocardial infarction (n=12).

Results:
Although glucose uptake was similar, glucose was redirected to fatty acid synthesis, the polyol pathway, and the PPP, and away from oxidative metabolism in Pkm2 KO cardiomyocytes. Despite the increased flux into the PPP, NADPH production was low. Assessment of ROS levels in normoxia revealed that Pkm2 KO cardiomyocytes had higher levels of ROS, possibly stimulating the inflammatory response in Pkm2 KO mice. CRP levels were higher in Pkm2 KO plasma at baseline. ROS remained high in Pkm2 KO cardiomyocytes after hypoxic treatment and CRP remained high in Pkm2 KO plasma after MI.

Conclusions:
Increased expression of Pkm1 in the Pkm2 KO mice increases flux of metabolites through oxidative metabolism, exacerbating mitochondrial ROS and activating the PPP. Although NADPH levels should have correlated with increased PPP flux, the low NADPH production in Pkm2 KO cardiomyocytes suggest rapid consumption of NADPH by ROS and fatty acid synthesis. This study suggests a role for hypoxia-stimulated PKM2 accumulation in stabilizing glucose flux to mitigate oxidative stress in the ischemic heart.
Abstract 10733: Health Status Outcomes by Race in Patients Treated With Sodium-Glucose Cotransporter 2 Inhibitors: A Pooled Patient-Level Meta-Analysis of CHIEF-HF, DEFINE-HF, and PRESERVED-HF
Authors: Gupta Kashvi , Spertus John , Birmingham Mary , Gosch Kensey , Januzzi James L , Lingvay Ildiko , Butler Javed , Kosiborod Mikhail N , Lanfear David E
Published: June 2023

Introduction
Black patients with heart failure (HF) have worse health status (symptoms, function, and quality of life) compared with White patients. Reducing this disparity is a national priority. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) not only improve cardiovascular mortality and hospitalization rates in HF patients regardless of ejection fraction (EF) but also improve patients’ health status. However, because Black patients have not been well represented in global HF outcomes trials, whether the benefits of SGLT2i on health status are consistent in patients with HF regardless of race is not well understood.

Methods
We combined patient-level data from three US randomized, double-blinded clinical trials of SGLT2i vs. placebo, DEFINE-HF (n=263), PRESERVED-HF (n=324), and CHIEF-HF (n=448). All three trials collected the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline and 12-weeks after treatment initiation. We assessed the change in the KCCQ clinical summary score (CSS, which comprises symptoms and physical limitations) by treatment arm in White and Black participants and tested the interaction of treatment by race using multivariable linear regression adjusting for trial and baseline KCCQ scores (as a restricted cubic spline).

Results
Among 935 participants, 236 (25%) self-identified as Black, and 469 (50.2%) were treated with an SGLT2i. Treatment-related changes in the KCCQ by race are summarized in the Table. Treatment with an SGLT2i vs. placebo resulted in 4.7-point improvement in CCS in Black patients (95% CI 0.74, 8.68; p= 0.02) and 4-point improvement in White patients (95% CI 1.69, 6.29; p=0.0007), with no treatment benefit heterogeneity by race (interaction p-value = 0.76).

Conclusions
The health status benefits of SGLT2i are consistent in Black and White patients. Therefore, whether improved access to SGLT2i can reduce HF-related health status disparities in Black patients should be tested.
Abstract 10734: Percutaneous Closure of Aorto-Right Atrial Fistula: An Interesting Case of Marfan’s Syndrome and Fistula Formation
Authors: Mahmood Ahmed , Nadipalli Vivek , Lodhi Muhammad Uzair , Hussain Bilal , Vargas Carlos E , Khan Sohail , cuevas christel , Alexander Thomas
Published: June 2023

Case Presentation:
A 43-year-old male with a history of Marfan’s syndrome, coronary artery disease and mitral valve endocarditis status-post mitral valve annuloplasty was admitted with NYHA class IV symptoms and cardiogenic shock. Two distinct color-flow jets on transesophageal echocardiography (TEE) supported evidence for fistulae formation at the aortic sinus and the right atrium (RA). After stabilization, closure options were discussed with the patient and a multi-disciplinary team including a cardiothoracic surgeon, structural heart disease specialist and heart failure specialist. Shared decision for percutaneous closure of the fistula was made. Figure 1A, demonstrates a peri-operative TEE with two distinct fistulae with color-flow jets emanating from the sinus of Valsalva into the RA. Each fistula orifice measured approximately 3mm in diameter with 5mm of separation. Under fluoroscopy, trans-aortic wire and sheath were used to cross a single fistula into the RA. An 18mm occluder device (Figure 1B and 1C), was deployed via transaortic into the RA. Intracardiac echocardiography revealed good device position and trivial jet. Post-operative TEE verified successful occlusion of both fistula. The patient tolerated the procedure and was discharged. He was seen in clinic two weeks post-discharge and reported resolution of his dyspnea.

Conclusion:
Aorto-atrial fistulas (AAF) are rare, complex and life-threatening; however, potentially treatable conditions. While most cases are acquired, congenital causes exist. This is an interesting case that illustrates a unique presentation of a rare condition and showcases potential for endovascular treatment. There are no randomized clinical trials and more scientific evidence is required to establish recommendations for a diagnostic and treatment algorithm. Until then clinical judgment with consideration for percutaneous closure seems a viable option.
Abstract 10754: AMPKγ2 Deficiency Exacerbates Macrophage Recruitment and Inflammation Post-MI via Promoting YY1-CXCL16-CXCR6 Axis
Authors: Song Ziping , Liu Dan , Yan Bing , song haixu , Zhang Yan , Cai Yi , Zhao Xiaojie , Tian Xiaoxiang , Yan Chenghui , Han Yaling
Published: June 2023

Background:
Acute myocardial infarction (MI) has got revolutionized therapeutic strategy by applying timely reperfusion therapy in a particular increase of primary percutaneous coronary intervention. Despite this cardiac remodeling following MI are very common with high mortality. A previous study claimed that AMPK played a pivotal role in intracellular adaptation to energy stress during myocardial ischemia. However, whether AMPKγ2 subunit played an important role in MI remains poorly defined.

Hypothesis:
We assessed the hypothesis that AMPKγ2 played an important role in regulating MI.

Methods:
AMPKγ2 level in monocytes of myocardial infarction patients was tested by ELISA. Ligation of left anterior descending branch (LAD) surgery was conducted to establish MI model. Lyz2-cre AMPKγ2 and AAV carrying F4/80 promoter for macrophage-specific overexpression AMPKγ2 mice were employed to investigate the role of AMPKγ2 in macrophages derived from MI.

Results:
AMPKγ2 was relatively highly expressed in the spleen and macrophage. Lyz2-cre AMPKγ2 mice developed worse cardiac dysfunction post-MI by boosting macrophage infiltration and inflammation. Overexpression of AMPKγ2 in macrophages repressed its migration and inflammation and alleviated myocardial injury. Mechanistically, CXCL16-CXCR6 axis was the contributor to macrophage migration, which was alleviated by AMPKγ2 via transcriptional regulation. Further, AMPKγ2 restrained YY1 expression, a key upstream transcription factor of CXCL16, to block the migration of macrophages. AMPKγ2 promoted YY1 degradation via smurf2 mediating ubiquitin-proteasome pathway depending on AMPKα1 subunit-mediating AMPK activity. Therefore, A769662 but not Metformin alleviated AMPKγ2 deficiency-induced migration and inflammation in macrophages. Finally, IFN-γ downregulated HOXA5 to repress AMPKγ2 transcriptional activity. Consistently, AMPKγ2 was dramatically declined in monocytes of MI patients compared to the control group.

Conclusion:
Macrophage AMPKγ2 deficiency played an important role in cardiac dysfunction following MI by activating the YY1-CXCL16-CXCR6 axis, which can be developed as a precision therapeutic target to ameliorate cardiac remodeling post-MI.
Abstract 10765: Association Between Prehospital Nitroglycerin and Clinical Outcome in Acute Coronary Syndrome
Authors: Komaki Soichi , TOKAI TATSUYA , Kaichi Ryota , Takae Masafumi , Mori Takayuki , Toida Reiko , Kurogi Kazumasa , Yamamoto Nobuyasu , Tsujita Kenichi , TSURUDA Toshihiro , Kaikita Koichi
Published: June 2023

Introduction:
Whether prehospital Nitroglycerin use is associated with major adverse cardiac events (MACE) remains unknown in the era of primary percutaneous coronary intervention (PCI) using stents.

Hypothesis:
We hypothesized that prehospital Nitroglycerin use would be associated with MACE in acute coronary syndrome (ACS) patients who underwent primary PCI.

Methods:
This retrospective observational study enrolled 947 consecutive patients who received the emergent PCI. Patients were classified into the two groups, with and without prehospital Nitroglycerin use. 250 patients were given prehospital Nitroglycerin sublingually or via oral spray or intravenously. The clinical outcome was MACE defined as a composite of all-cause death, myocardial infarction, and stroke at a one-year follow-up.

Results:
The Systolic blood pressure at the emergency department was 132 (105, 141) mmHg in the prehospital Nitroglycerin, and 135 (113, 158) mmHg in the non-Nitroglycerin group (P < 0.001). Kaplan-Meier survival curves revealed that the MACE frequency was higher in the prehospital Nitroglycerin group (p = 0.021). Multivariate Cox regression analysis revealed that the prehospital Nitroglycerin use (hazard ratio, 1.65; 95% confidence interval [CI], 1.02-2.65; p = 0.002) was an independent predictor for MACE. Prehospital Nitrogricerin use, Killip classification, and Ejection fraction models resulted in a c-statistic with a statistically significant 95% PI and moderate discriminative performance (c-statistic=0.763; 95% CI, 0.7111-0.816, p<0.001).

Conclusions:
The present results suggested that the prehospital Nitroglycerin use might worsen the one-year prognosis in ACS patients undergoing primary PCI.
Abstract 10768: Double Whammy: An Unusual Case of Mycotic Abdominal Aortic Aneurysm in a Bacteremic Patient - Case Report
Authors: Valdez Maria Monica , Rubiano Dana Rosielou L , Yamamoto Milagros E , Yamamoto Jose S
Published: June 2023

Introduction:
Ruptured mycotic aortic aneurysm is a relatively rare, life-threatening disease, which is associated with remarkable mortality. In East Asia, mortality caused by this disease is high and it is commonly caused by Salmonella species. Majority of cases of mycotic aneurysms caused by Salmonella were in the abdominal aorta wherein most of them presented with chills and fever while some presented with diarrhea from 2 days to 1 month before the aneurysm was diagnosed. Patients who present with diarrhea and abdominal pain are likely to be missed. It is therefore important that mycotic abdominal aneurysm be recognized early, and prompt treatment be initiated.

Case:
A 78-year-old American male, Philippine immigrant with history of ischemic stroke and chronic smoking presented with diarrhea and severe abdominal pain. Complete blood count showed leukocytosis with neutrophilic predominance. A computed tomography scan of whole abdomen exhibited a fusiform aneurysm of the infrarenal abdominal aorta with large periaortic hematoma indicating prior rupture. Open abdominal aortic aneurysm repair was successfully done and intravenous Meropenem and Ciprofloxacin were given. Blood, urine, thrombus, and aortic plaque cultures were obtained and all revealed Salmonella specie with same antibiogram. Intravenous Meropenem and Ciprofloxacin was transitioned to intravenous Ceftriaxone and was continued for 6 weeks post-operatively.

Conclusion:
Mycotic abdominal aortic aneurysm can be diagnosed with the combination of clinical symptoms, laboratory, radiological findings, and intraoperative findings. However, vague and non-specific symptoms do not rule out the diagnosis. High index of suspicion and low threshold for CT imaging is necessary in any patient age >60 years who present with abdominal pain and with previous history of gastroenteritis. Prompt initiation of antibiotic therapy and surgical intervention are the treatment of choice.
Abstract 10769: Circulating Branched-Chain Amino Acids, Incident Cardiovascular Disease, and Mortality in the African American Study of Kidney Disease and Hypertension
Authors: Luo Shengyuan , Surapaneni Aditya , Rebholz Casey , Appel Lawrence J , Coresh Josef , Grams Morgan
Published: June 2023

Introduction:
Branched-chain amino acids (BCAAs), i.e., leucine, isoleucine, and valine, are involved in glucose regulation, immunity, and cell signaling. Higher circulating BCAAs were associated with incident cardiovascular disease (CVD) in the general population which may be mediated by insulin resistance. BCAA’s role in CVD in the absence of diabetes is unclear.

Hypothesis:
BCAAs are associated with cardiovascular outcomes in non-diabetic chronic kidney disease (CKD), a highly prevalent condition that substantially alters circulating metabolites and elevates CVD risk.

Methods:
In the African American Study of Kidney Disease and Hypertension (AASK), we conducted serum metabolomic profiling and assessed associations between BCAAs and risks for incident CVD (hospitalization for nonfatal myocardial infarction, cardiac revascularization, heart failure, stroke, or cardiovascular death), cardiovascular death, and all-cause mortality using multivariable Cox regression.

Results:
In 962 participants (mean age 56 years, 39% women, mean glomerular filtration rate [GFR] 48 ml/min/1.73m
2
, mean fasting blood glucose 94 mg/dl, mean low density lipoprotein cholesterol [LDLc] 137 mg/dl), BCAAs were minimally correlated with GFR, proteinuria, C-reactive protein, LDLc, or blood glucose. During follow-up (median 7.4 years), there were 192 CVD events (myocardial infarction or revascularization, n=57; stroke, n=74; heart failure, n=74) and 220 deaths of which 54 were cardiovascular deaths. Adjusted for covariates, no association was found between BCAAs and incident CVD, but higher BCAAs were associated with lower cardiovascular death (per doubling BCAA, HR=0.52, 95%CI 0.31-0.87; p=0.013 for isoleucine; HR=0.30, 95%CI 0.13-0.68, p=0.004 for leucine, HR=0.39, 95%CI 0.16-0.94, p=0.04 for valine). Associations were unchanged accounting for all-cause death as competing risk using Fine-Gray modeling. Leucine and isoleucine were associated with lower all-cause mortality (HR=0.57, 95%CI 0.36-0.96, p=0.035 for leucine; HR=0.70, 95%CI 0.49-1.00, p=0.049 for isoleucine).

Conclusions:
In African Americans with non-diabetic CKD, higher circulating BCAAs were associated with lower cardiovascular death, lower mortality, but not incident CVD.
Abstract 10788: Identifying Clinical and Demographic Factors Associated With Sub-Optimal Statin Prescription Rates Following Carotid Endarterectomy
Authors: Eppler Michael , Singh Nikhil , Ding Li , Magee Gregory , Garg Parveen
Published: June 2023

Introduction:
Statin therapy is under prescribed in patients undergoing carotid endarterectomy (CEA). We determined new statin prescription rates following CEA as well as the demographic, clinical, and procedural characteristics associated with likelihood of new prescription.

Methods:
A retrospective Vascular Quality Initiative analysis of patients undergoing CEA and not on statin therapy pre-procedure between 2013 to 2021 was performed. Multivariate logistic regression was used to determine patient characteristics associated with new statin therapy.

Results:
Participants undergoing CEA were predominantly male (61%) and white (90%), with a mean age of 70.6 ± 9.1 years. Of all eligible subjects, 13.2% were not on statin therapy at time of CEA, corresponding to 15,733 procedures. New statin therapy was prescribed following 48% of these procedures, with rates increasing throughout the study period (36.2% in 2013 to 62% in 2021) (Figure). A higher likelihood of new statin prescription was associated with non-white race (Asian vs. White (Relative Risk (RR) 1.13; 95% Confidence Interval (CI) 1.06-1.20); Black vs. White (RR 1.26; 95% CI 1.11-1.43)), diabetes (oral medications vs. no diabetes (RR 1.06; 95% CI 1.02-1.11)), coronary heart disease (RR 1.12; 95% CI 1.08-1.16), prior stroke (RR 1.29; 95% CI 1.22-1.37), TIA (RR 1.07; 95% CI 1.00-1.13), and a non-elective indication (elective vs. emergent (RR 1.39; 95% CI 1.27-1.53)). A lower likelihood of new statin prescription was associated with older age (≥77 vs. ≤65 (RR 0.88; 95% CI 0.84-0.93)), female gender (RR 0.95; 95% CI 0.92-0.99), COPD (RR 0.95; 95% CI 0.91-0.99), and prior carotid revascularization (RR 0.87; 95% CI 0.82-0.92).

Conclusions:
A significant percentage of patients are not on a statin at the time of CEA, and of those, only 48% are discharged on one. System-wide and provider-focused efforts are needed to identify shortcomings in the introduction of this cardioprotective medication into standard of care.
Abstract 10789: Disruption of Stromal Interaction Molecule 1 in Immune Regulatory T Cells Protects Vascular Endothelial Function in Renovascular Hypertension
Authors: Matrougui Khalid , SRINIVAS BALAJI , Alluri Kiran , O'Regan Jacob D , Belmadani Souad
Published: June 2023

Introduction & Hypothesis:
Microvascular dysfunction in renovascular hypertension is a major risk factor for cardiovascular diseases. However, the underlying mechanism of vascular endothelial dysfunction in renovascular hypertension is not fully understood. Here, we sought to determine the role and impact of the stromal interaction molecule 1 (STIM1) knockout in immune regulatory T cells (Stim1
Treg-/-
) in renovascular hypertension-induced vascular endothelial dysfunction.

Methods:
Mice were divided into four groups. Group 1 and 2: Stim1
flx/flx
male and female mice with and without 2-kidney-1-clip (2K1C) surgery for four weeks. Group 3 and 4: Stim1
Treg-/-
male and female mice with and without 2K1C for four weeks. We measured body weight, arterial blood pressure, cardiac hypertrophy, lung edema, inflammation, fibrosis, and assessed microvascular endothelial function.

Results:
Stim1
flx/flx
both male and female mice subjected to 2K1C for four weeks develop hypertension, cardiac hypertrophy, lung edema, low running performance, and vascular dysfunction. Interestingly, the disruption of STIM1 in Treg cells in both male and female mice protected from 2K1C-induced hypertension, cardiac hypertrophy, and lung edema. Moreover, microvascular endothelial function was also protected in both groups.

Conclusion:
Our data illustrate that STIM1 in immune Treg cells has s significant impact in renovascular hypertension-induced cardiovascular complications. Thus, targeting STIM1 in Treg cells could be a potential therapeutic approach to protect from renovascular hypertension-induced cardiovascular diseases.
Abstract 10822: Familial Hypercholesterolemia in the EMERGE Network: 1-Year Outcomes After Return of Results
Authors: Sherafati Alborz , Dikilitas Ozan , Saadatagah Seyedmohammad , Satterfield Benjamin , Kochan David , Jones Laney , Perez Emma , Anderson Katherine , Salvati Zachary , Hebbring Scott , Sharp Richard , Sturm Amy , Gibbs Richard , Linder Jodell , Zouk Hana , Venner Eric , Chung Wendy , Peterson Josh , Jarvik Gail , Rehm Heidi , Roden Dan M , Williams Marc , Manolio Teri A , Kullo Iftikhar J
Published: June 2023

Introduction:
Relatively little is known about outcomes following return of secondary findings detected in large scale sequencing projects. We assessed 1-year outcomes following return of pathogenic/likely pathogenic (P/LP) variants associated with familial hypercholesterolemia (FH) in phase III of the eMERGE network (2015-2019).

Methods:
Adult participants (n=18,544) at 7 sites were enrolled in a prospective cohort study to study the clinical impact of returning results from targeted sequencing of 68 actionable genes, including
LDLR
,
APOB
, and
PCSK9
. Process, intermediate, and/or clinical outcomes within 1-year after return of results (RoR) were ascertained by electronic health record (EHR) review. A process outcome was defined as referral to a specialist or ordering new tests, including lipid profile and screening tests for coronary heart disease. An intermediate outcome was defined as new diagnosis of FH or atherosclerotic cardiovascular disease. A clinical outcome was defined as initiation or change in lipid-lowering medication. The primary outcomes were a new diagnosis of FH and modification of lipid lowering therapy.

Results:
Results were returned to 134 individuals, and data for 119 participants were available for the outcomes analysis. Process (86%), intermediate (49%), and/or clinical (26%) outcomes occurred in 92% of participants. Process outcomes included 72% with new tests ordered and 61% referred to a specialist. Before RoR, 86.5% of individuals with FH associated P/LP variants had a diagnosis of hypercholesterolemia but only 17.6% had a diagnosis of FH; 89% were on a statin but only 58% were on a high intensity statin. Following RoR, 44% (52/119) received a new diagnosis of FH. Lipid lowering treatment was modified in 26% (31/119), including initiation of a statin in 5%, increasing statin dose in 13%, and adding ezetimibe or a PCSK9 inhibitor in 12.6%.

Conclusions:
In a multisite cohort of EHR-linked biobanks, monogenic FH was underdiagnosed (only 17.6% had a specific diagnosis) and undertreated (only 58% were on a high intensity statin); 44% of participants received a new diagnosis of FH and 26% had lipid lowering treatment modified after RoR. These results highlight the clinical utility of returning FH variants in EHR-linked biobanks.
Abstract 10825: Tumor-Bearing Induces Cardiomyopathy by Disrupting Cardiometabolic Reprogramming
Authors: Yang Ming , xiong shijie , Tan Jing , li yuanlong , Shen Conghui , Wu Teng , fu xinlu , feng ziqi , ji yuanjun , zheng huiting , cai weibin
Published: June 2023

Introduction:
Advances in cancer therapies have significantly improved patient survival. However, prolonged tumor-bearing (TB) survival makes the originally hidden cardiovascular disease become an increasingly important cause of death in tumor patients. In addition, some commonly used chemotherapeutic agents, such as the doxorubicin (DOX), have definite cardiotoxicity. Moreover, epidemiological studies found higher risks of cardiovascular disease in cancer patients than in the general population. This study aimed to investigate the if the TB state leads to cardio-fragility and myocardial sensitivity which further causes excessive cardiotoxicity of DOX in tumor patients.

Methods and Results:
We established mouse TB models with six types of transplantation tumors. We administrated them and littermate controls with DOX intraperitoneal injections of 10mg/kg weekly for four weeks. The results showed more severer myocardial injury in TB mice than control group based on the echocardiography, cardiac fibrosis, and etc. The RNA-seq, extracellular flux analysis, and PET-CT indicated an increased proportion of myocardial glycolytic metabolism in the TB state. Furthermore, the Secretomic results of clinical cancer patients and control group, along with the Co-IP of TB mice, showed that the TB state induced hyper-phosphorylation of protein tyrosine residues in cardiomyocytes (CMs) via the increase of secreted growth factors, which introduced an elevated expression of pyruvate kinase muscle 2 (PKM2) and increased the proportion of dimer conformation. Meanwhile, those changes allowing re-entry of CMs into the cell cycle and further increased DNA damage co-localization with EdU, eventually led to excessive cardiotoxicity in the TB state by DOX. Finally, treatment with AG-1478 or TEPP-46 with DOX restricted the cardiotoxicity in the TB state, which meanwhile enhanced the tumor-suppressive effect in lung cancer and melanoma models.

Conclusion:
Our study reveals that differences in tyrosine phosphorylation of CMs between TB and normal states could cause metabolic pattern shift and cell cycle re-entry in CMs. The increased cardio-fragility induced by TB state may be involved in the enhanced cardiotoxic side effects of chemotherapeutics.
Abstract 10849: Clinical Outcomes at Medium-Term Follow-Up of COVID-19
Authors: Xuereb Rachel Anne , Barbara Jessica , Gatt Jessica , Tabone Adami Nicholas , Darmanin Jessica , Erasmi Renee , Xuereb Robert G , Stephen Fava , Magri Caroline J
Published: June 2023

Introduction:
Long COVID syndrome is defined as physical, cognitive and psychological symptoms that persist for over 12 weeks following the acute illness and are not explained by other diagnosis.

Aim:
To assess medical and health-related quality of life (HR QOL) outcomes at medium-term follow-up in subjects previously infected with COVID-19.

Methods:
2646 patients who were diagnosed with COVID-19 infection were randomly selected. They were interviewed to assess for symptoms and HR QOL using a post-COVID questionnaire and Short Form Survey (SF-36) respectively. Blood investigations were taken.

Results:
The median age was 44 years (IQR 31-55), 49% were males. 5% were hospitalised and 1% intubated. Smokers comprised 17%, 10% were ex-smokers. 17% suffered from hypertension, 11% hyperlipidaemia, ischaemic heart disease was present in 2%, heart failure in 1%, obesity in 18%, chronic kidney disease in 0.2%, chronic respiratory disease in 7% and type 2 diabetes mellitus (DM) in 7%.

Median time to follow up was 142 days (IQR 128-161). 22% of participants claimed they felt worse than before. Most common symptoms were anosmia (55%), abnormal taste (53%), fatigue (23%), dyspnoea (23%), headache (20%) and myalgia (15%). The SF-36 survey showed that hospitalized patients fared worse in all domains except for role-emotional.

New onset DM was diagnosed in 50 patients, similar to the rate of undiagnosed DM in the population. Hospitalised patients had significantly higher liver transaminases, FPG, HbA1c, uric acid, RDW, MPV, triglyceride levels and troponin levels but lower eGFR and HDL-cholesterol at follow-up. The differences in RDW, MPV, triglyceride, GGT and FPG remained significant after adjusting for confounders (Table 1).

Conclusions:
A significant proportion of post-COVID patients were symptomatic at medium-term follow-up. Hospitalised patients had more biochemical and haematological abnormalities, suggesting ongoing inflammation in those more severely affected.
Abstract 10855: Murine Model of Phenylhydrazine-Induced Chronic Hemolytic Anemia Leads to Development of Early Pulmonary Hypertension
Authors: Gonzales Janae , Humpal Cat , CHEN Weiguo , Epshtein Yulia , Fraidenburg Dustin R
Published: June 2023

Introduction:
Pulmonary hypertension (PH) in sickle cell disease is associated with high morbidity and early mortality, yet the pathogenesis remains incompletely understood.
In vitro
data by our group implicates extracellular hemoglobin in the endothelial dysfunction that leads to precapillary vascular changes seen in PH and identifies endothelial to mesenchymal transition (EndoMT) as a likely mechanism. To support these findings, we hypothesize that a murine model of chronic hemolysis will show signs of EndoMT and early development of PH.

Methods
C57BL/6J mice were treated with 40 mg/kg of phenylhydrazine (PHZ), a toxin known to induce hemolysis, or saline, as control, twice a week for three weeks. Plasma cytokine concentrations and complete blood counts were measured. Non-invasive and invasive measures of PH were obtained by echocardiography (TTE), hemodynamic pressure assessments, and measures of right ventricular (RV) hypertrophy. Explanted lung tissue was homogenized and subjected to Western blot analysis to evaluate markers of EndoMT.

Results
PHZ administration causes anemia (9.1 g/dL vs 11.4 g/dL in control mice) without a significant drop in other hematopoietic cell lines. PHZ-treated mice have increased plasma cytokines CXCL1 and IL-6, which are known to be upregulated in PH. TTE shows significantly decreased pulmonary artery acceleration time (16.7 vs 19.5 msec, p < 0.05), and a trend toward decreased tricuspid annular plane systolic excursion in PHZ-treated mice (0.9 vs 1.2 mm). Invasive hemodynamics show a slight increase in right ventricular systolic pressure (25.6 vs 23.4 mm Hg) and analysis of RV hypertrophy shows increased Fulton index in PHZ-treated mice compared to control (0.28 vs 0.24). Western blot analysis of lung tissue shows upregulation of EndoMT transcription factor SNAI2 in PHZ-treated mice versus control.

Conclusions
PHZ-treated mice demonstrate early invasive and non-invasive signs of PH with upregulation of EndoMT transcription factor SNAI2, suggesting a relationship between hemolysis, EndoMT, and the development of PH. PHZ administration may be a novel murine model for PH due to chronic hemolysis, facilitating pathobiological and therapeutic discovery for this devastating complication of sickle cell disease.
Abstract 10856: Artificial Intelligence-Guided Screening for Atrial Fibrillation Using the Electrocardiogram in Sinus Rhythm
Authors: Noseworthy Peter A , Attia Zachi I , Behnken Emma M , Giblon Rachel E , Bews Katherine A , Liu Sijia , Gosse Tara , Linn Zachery D , Deng Yihong , Yin Jun , Gersh Bernard J , Graff-Radford Jonathan , Rabinstein Alejandro A , Siontis Konstantinos , Friedman Paul , Yao Xiaoxi
Published: June 2023

Introduction:
Prior AF screening trials demonstrated low yield, highlighting the need for more targeted approaches. An AI algorithm was developed to identify ECG signatures of AF risk during normal sinus rhythm, which has been validated in diverse external populations.

Hypothesis:
An AI-guided, targeted screening approach could improve the diagnosis of AF.

Methods
We conducted a pragmatic decentralized trial to prospectively recruit patients with stroke risk factors but no prior AF. The AI algorithm was applied to the ECGs performed in routine practice and divided patients into high- or low-risk groups. The primary endpoint was AF lasting ≥ 30 seconds on a subsequent 30-day continuous cardiac rhythm monitor. In a secondary analysis, trial participants were 1:1 propensity score-matched to real-world controls derived from the eligible but unenrolled population.

Results
A total of 1,003 patients from 40 U.S. states completed the study, with a mean age of 74 [SD 8.8] years. Over a mean of 22.3 days of continuous monitoring, AF was detected in 6 (1.6%) of low-risk patients and 48 (7.6%) of high-risk patients (OR 4.98 [2.11-11.75], p<0.001). Compared to usual care, AI-guided AF screening was associated with increased detection of AF (high-risk group: 4.2% vs. 11.1%, p<0.001; low-risk group: 0.9% vs. 2.4%, p=0.12) over a median follow-up of 10 months.

Conclusions
A prospective pragmatic study found that the AI a can risk-stratify a relatively uniform population (i.e., older adults at risk for stroke) to detect AF during short-term cardiac monitoring. Furthermore, when compared with usual care, AI-guided cardiac monitoring was associated with increased AF detection. As such, an AI-guided AF screening approach, leveraging existing EHR data and infrastructure, could be effective, patient-centered, and massively scalable, thereby reducing unnecessary health utilization and diagnosis-related anxiety (Clinicaltrials.gov: NCT04208971).
Abstract 10889: Unplanned Limb Revascularization With Rivaroxaban versus Placebo in Patients With Critical Limb Ischemia After Endovascular and Surgical Treatment: Insights From Voyager Pad
Authors: Hogan Shea E , Patel Manesh R , Debus Sebastian , Nehler Mark , Anand Sonia S , Canonico Mario Enrico , Hess Connie N , Rogers R. Kevin , Hsia Judith A , Muehlhofer Eva , Haskell Lloyd P , Berkowitz Scott D , Bauersachs Rupert , Bonaca Marc P
Published: June 2023

Introduction:
Patients with critical limb ischemia (CLI) have a class I indication for lower extremity revascularization (LER) by either endovascular or surgical approach. A common complication is recurrent arterial occlusion requiring unplanned index limb revascularization (UILR). VOYAGER PAD established the efficacy of rivaroxaban in patients with symptomatic peripheral artery disease (PAD) after successful LER, including a reduction in UILR. Whether this benefit differs by LER approach for CLI is unknown.

Hypothesis:
Rivaroxaban reduces UILR regardless of LER approach for CLI.

Methods:
LER indication (CLI or claudication) and approach were captured at baseline. The primary composite endpoint was acute limb ischemia, major vascular amputation, MI, ischemic stroke or CV death. TIMI major bleeding was the primary safety outcome. UILR was a prespecified secondary outcome. A Cox proportional-hazards model was used to calculate hazard rations and 95% confidence intervals.

Results:
Among 6,564 participants randomized
,
1,533 (23%) had CLI, of whom 696 (45%) and 837 (55%) underwent surgical and endovascular LER, respectively. CLI patients on rivaroxaban had fewer events at three years compared to those on placebo (HR 0.85). Efficacy of rivaroxaban for the primary endpoint (p-interaction 0.40) and safety (p-interaction 0.18) in CLI were consistent regardless of approach. On background therapy (aspirin in all, statins ~80%, DAPT ~50%), at a median of 28 months, UILR occurred in 26.2% and 14.3% after endovascular and surgical LER, respectively. Rivaroxaban significantly reduced UILR by 22% in patients with CLI (HR 0.78, p=0.019, Figure), with consistent benefits in those treated with endovascular and surgical LER (p-interaction 0.70).

Conclusions:
CLI patients have high rates of UILR after LER. Rivaroxaban reduced the rate of UILR in this population, regardless of endovascular or surgical approach.
Abstract 10922: Maternal Hypercholesterolemia Induces Changes in DNA Methylation Pattern of Lipid Metabolism Genes in the Human Placenta
Authors: VS JAYALEKSHMI , BASU BUDHADITYA ,   KIMS Investigators, RAMACHANDRAN SURYA
Published: June 2023

Introduction:
Maternal hypercholesterolemia (MHC) during gestation is reported to enhance formation of fatty streaks in human fetuses leading to atherosclerosis in their adulthood. As maternal lipid levels increase during gestation as a normal physiological response to growing fetus, cholesterol levels are not routinely monitored in the outpatient clinic. The mechanisms mediating the stimulus transferred from hypercholesterolemic mothers to the fetus resulting in atherogenesis remains to be delineated.

Hypothesis:
We hypothesize that high lipid levels of hypercholesterolemic mother program the fetus by causing changes in DNA methylation patterns of lipid transport and metabolism genes in the placenta.

Methods:
Pregnant females within 100 days of first pregnancy were recruited. Total cholesterol (TC) and Low Density Lipoprotein (LDL) levels above 200mg/dL and 130mg/dL respectively were considered as hypercholesterolemic (MHC; n=50). Pregnant mothers with normal cholesterol levels were also recruited (NC; n=50). Lipid profiling of maternal blood was performed in all trimesters. Cord blood at the time of birth and neonatal blood on the 2
nd
day post birth were also profiled. DNA methylation array was performed in the placenta of MHC and NC mothers post delivery. Data were analyzed using RnBeads and Limma package. Data were validated by qRT PCR and immunohistochemistry of placental tissues.

Results:
Lipid profiling revealed high TC and LDL levels in MHC mothers and high triglycerides in their neonates on the 2
nd
day post birth. There were 3789 differentially methylated gene sets reported in the placenta of hypercholesterolemic mothers of which, 167 genes were hypomethylated and 94 genes were hypermethylated in the CpG islands. The hypermethylation and downregulation of lysosomal lipase genes (LIPA) was observed in the placenta of MHC mothers. This was complemented by upregulated expression of PEX11A, a peroxisomal biogenesis factor and ABCD1 which is a fatty acid transporter.

Conclusions:
We report the hypermethylation of lysosomal lipid degradation genes and hypomethylation of peroxisomal genes in the placenta of MHC mothers. This results in high triglycerides in neonates with a risk for early atherogenesis in adulthood.
Abstract 10949: Standard Modifiable Cardiovascular Risk Factors and Long-Term Clinical Outcomes Among Patients With ST-Elevation Myocardial Infarction
Authors: Singh Yu Suresvar , Wada Hideki , Ogita Manabu , Nakamura Yutaka , Sohshi Moriya , Ishikawa Goh , Yasuda Kentaro , Shitara Jun , SUWA Satoru , MIYAUCHI Katsumi , Minamino Tohru
Published: June 2023

Background:
Little is known about the association between standard modifiable cardiovascular risk factors (SMuRFs; hypertension, diabetes, dyslipidemia, and smoking) and clinical outcomes among patients with STEMI.

Methods and Results:
STEMI patients who underwent primary PCI were enrolled. Primary endpoint was all-cause death. Between 1999 and 2015, 126 (6.4%) of 1,963 patients with STEMI had no SMuRFs. Patients without SMuRF were significantly older and more likely to be female. During median follow-up period of 4.8 years, cumulative incidences of death were significantly higher in patients without SMuRF (log-rank p<0.0001). Multivariate Cox hazard analysis showed that patients without SMuRF had significantly higher risk of mortality (HR 1.41, 95%CI 1.07-1.86, p=0.01).

Conclusions:
STEMI patients who didn’t have SMuRFs had worse clinical outcomes compared with those with at least one SMuRFs.
Abstract 10950: Prognostic Utility of Left Atrio-Ventricular Deformation Analysis in Heart Failure Patients Underwent Cardiac Resynchronization Therapy
Authors: Sugahara Masataka , Min Kyung-Duk , Mine Takanao , Asakura Masanori , Ishihara Masaharu
Published: June 2023

Introduction:
Left atrial (LA) adverse remodeling is a prognostic marker in patients with heart failure. Although left ventricular (LV) deformation analysis by speckle tracking method has been shown as a useful predictive marker after cardiac resynchronization therapy (CRT), the prognostic impact of baseline left atrio-ventricular functional deterioration on the outcome of patients underwent CRT implantation.

Hypothesis:
We hypothesized that a combination of LV and LA deformation assessments by speckle-tracking strain is of additive prognostic value in patients with CRT.

Methods:
We retrospectively analyzed 71 participants who received CRT implantation in the clinical guidelines. Global longitudinal strain (GLS) was defined as averaged strain from 3 apical views. LA strain (LAS) was calculated as the average strain using apical two- and four-chamber views. The endpoint was composite outcome of death, hospitalization due to worsening HF for 5 years after CRT implantation.

Results:
Out of 71 patients aged 68 ± 11 years with 162±24ms of QRS duration and 30±8% of LV ejection fraction, 40 patients (56%) met the endpoint. The patients were stratified using median value of LAS (-15%) and GLS (-8%). LAS and GCS remained significantly associated with poor outcome after adjusting for LVEF (LAS hazard ratio, 0.92; p<0.001; GLS hazard ratio, 1.15; p = 0.01). Kaplan-Meier analysis showed that the subgroup of patients with both lower median values of LAS and GLS had the worst outcomes over 5 years (Figure, Log-rank, p = 0.008). In the sequential Cox model, predictive value of baseline LV ejection fraction (χ2 = 4.9) was improved by the addition of GLS (χ2 = 9.2, p = 0.037), and further improved by the addition of LAS (χ2 = 15.8, p = 0.005). C-statistics also improved from 0.62 to 0.73.

Conclusions:
Baseline left atrio-ventricular functional deterioration by deformation analysis were significantly associated with poor outcome after CRT implantation.
Abstract 11006: Fick’s versus Cardiac MRI Measured Pulmonary Blood Flow in Pre-Fontan Assessment
Authors: Langanecha Bhavikkumar , Chaturvedi Rajiv , Seed Mike , Lam Christopher Z , Yoo Shi-Joon
Published: June 2023

Background:
Fick’s principle (FP) is unreliable if there are two sources of pulmonary blood flow (Q
p
) with different saturations. We compared Q
p
and pulmonary vascular resistance (PVRI) measured by cardiac MRI (CMR) and FP in pre-Fontan patients.
Material and Methods:
Retrospective analysis of CMR and catheterization data obtained under the same general anesthetic from Jan 2009 to March 2021. FP derived Q
p
and PVRI used assumed O
2
consumption from Sackler’s equation. Paired T test was used for comparison between FP and CMR parameters.

Results:
98 patients, with (mean ± sd): age 3.01±1.38 years and weight 13.31±2.4 kg. The FP derived Q
p
was 2.5(± 0.58) L/min/m
2
and PVRI1.91±0.61 Woods units*m
2
(WU*m
2
). CMR measured pulmonary arterial flow (Q
pa
) and pulmonary venous flow (Q
pv
) were 1.97±0.55 L/min/m
2
and 3.49±0.76 L/min/m
2
, respectively. The PVRI using CMR Q
pv
was 1.38±0.47 WU*m
2
. The paired mean differences between Q
p
by FP and CMR Q
pa
or CMR Q
pv
were 0.53 (95%CI 0.41, 0.66; p<0.001) and -0.98(95%CI -1.13, -0.83; p<0.001), respectively. The paired mean difference between PVRI by FP and PVRI by CMR Qpv was 0.53(95%CI 0.44, 0.61; p<0.001). The difference between CMR Q
pv
and FP derived Q
p
were correlated with aortopulmonary collateral flow (Pearson r=0.615, p<0.001). PVRI derived from FP (1.91±0.61 WU*m
2
) was higher than that from CMR (1.38±0.47, p<0.001). However, this only resulted in one FP based PVRI estimate being >4.0WU*m
2
when the CMR PVRI was <4.0WU*m
2
.

Conclusion:
s: FP derived Q
p
is lower than CMR Q
pv
resulting in higher PVRI estimates by FP. In most patients this will not affect clinical risk stratification based on PVRI. In high-risk candidates for the Fontan, CMR based flow measurements are preferrable.
Abstract 11046: Hospital Initiative to Increase Plant-Predominant Foods and Nutritional Education
Authors: Ahmad Sana , Gianos Eugenia , Hartog Katrina , Roach Nicole , Gierlinger Sven , Tison Bruno
Published: June 2023

Introduction:
Due to reduction in cardiovascular risk, healthy, plant-based foods, as opposed to animal-derived products should be promoted to patients. We created a hospital initiative on the cardiac floors to educate the multidisciplinary staff to serve as advocates for healthy eating. 

Methods:
Housestaff participated in education sessions on the benefits of plant-predominant meals and patient counseling. More plant-predominant options were added to the menu and several unhealthy items were eliminated. Food orders were assessed pre-intervention (February 2020) and post-staged interventions (October 2020 and April 2022). Food choices were assessed using the healthful and unhealthful diet index. Press Ganey scores were obtained and housestaff comfort with diet counseling was also assessed.

Results:
Resident perception of their own knowledge went from “poor” to “good” post-intervention. Confidence in talking to patients about plant-based diets went from “not confident at all” to “fairly confident".  After analysis of diet orders, a 52% decrease was noted in animal-based products (chicken, beef, pork and turkey), 35% decrease in unhealthful food items (refined grains, processed foods, potatoes and sweetened beverages), and 25% decrease in plant-predominant food items (whole grains, fruits, vegetables, nuts, salads, legumes and fish), but this time period occurred in the setting of high COVID-19 rates. A subsequent analysis of a single cardiac unit after the COVID-19 surges and after select unhealthy items were removed from the menu showed notable improvements in each parameter when adjusted for discharges; a 2% increase in plant-based, 37% decrease in animal based and 4% decrease in unhealthy items. Press Ganey ratings for the quality of food increased post-initiative by at least 27%.

Conclusions:
This quality initiative was a local pilot to increase our understanding of interventions that may have a meaningful impact on healthy eating for patients. Interpretation of results is limited due to the COVID-19 pandemic, which may have impacted food choices of admitted patients. Although further research is needed, housestaff engagement may be a promising mechanism to educate patients and encourage food and nutrition changes in a health system.