bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12131: LMO2 Regulates Endothelial Proliferation, Angiogenesis and Tissue Regeneration
Authors: Meng Shu , Matrone Gianfranco , Wong Wing tak , Cooke John
Published: April 2024

Introduction:
LIM domain only 2 (LMO2) is a key transcription factor of embryonic angiogenesis. However, its role in adult endothelial function and tissue regeneration is unclear.

Methods:
In vitro loss- and gain-of-function studies on LMO2 were performed in human umbilical vein endothelial cells (HUVEC) with lentiviral overexpression (OE) or shRNA knock down (KD) of LMO2 respectively. LMO2 gene expression and protein level was examined by RT-PCR and western blot respectively. Cell cycle was examined by PI staining and FACS analysis. Angiogenesis was examined by network formation assay on matrigel. ChIP-PCR was used to examine the LMO2 complex binding to chromatin. Vascular and tissue regeneration was examined by caudal fin regeneration in zebrafish model.

Results:
LMO2 KD impaired endothelial proliferation and angiogenesis. LMO2 controls the G1/S transition in endothelial cells through transcriptional regulation of CDK2 and CDK4 examined by RT, western blot and ChIP, and also influences the expression of CyclinD1 and Cyclin A1. LMO2 KD downregulated a network of angiogenic genes. Among them, LMO2 regulated TGFβ through binding to the proximal promoter of TGFB1. In a zebrafish model of caudal fin regeneration, lmo2 gene was upregulated at day 5 post resection. In this model, lmo2 KD by vivo-morpholino injection reduced BrdU incorporation in endothelial cells, impaired neoangiogenesis, and substantially delayed caudal fin regeneration.

Conclusions:
LMO2 is a critical transcription factor regulating adult endothelial proliferation and angiogenesis, and in adult animals regulates vascular and tissue regeneration.
Abstract 12144: Heterogeneity Between Rates of Hypertension Among Immigrant and U.S.-born Blacks: Pooled NHANES, 2003-2014 Data
Authors: Brown Alison G , Houser Robert L , Lichtenstein Alice H , Mattei Josiemer , Folta Sara C
Published: April 2024

Introduction:
Epidemiological data suggest that Blacks in the U.S. experience the highest prevalence of hypertension (44%) worldwide. It is unclear, however, if there are differences between U.S.-born and foreign-born immigrant Blacks. Since the passage of the Immigration and Nationality Act of 1965, a growing proportion of the U.S. Black population is made up of Black immigrants and it is predicted that by 2060, 16.5% of U.S. Blacks will be immigrants. Within the Black population, there are pronounced cultural differences in food preferences and physical activity habits, as well as social experiences, which are important risk factors for hypertension.

Methods:
Pooled NHANES data (2003-2014) for non-Hispanic immigrant Black adults aged 22-79y (n=515) and their US-born counterparts (n=4,249) were analyzed. Multivariable-adjusted logistic regression was used to investigate the association between nativity and odds for hypertension (defined as diagnosed hypertension, use of medication, or measured blood pressure ≥140/90mmHg). We also examined the association between length of U.S. residency among Black immigrants and hypertension.

Results:
Nearly half (48%) of US-born Blacks and 31% of immigrant Blacks had hypertension. Black immigrants were 42.4% less likely (OR 0.58, 95% CI 0.46, 0.72) to have hypertension than their U.S.-born counterparts. Length of U.S. residency was not associated with hypertension among Black immigrants.

Conclusions:
The likelihood of hypertension differs for immigrants versus U.S.-born Blacks. Considering place of birth among U.S. Blacks in epidemiological and public health research studies may help accurately characterize health disparities and develop targeted interventions to effectively address hypertension in this population.
Abstract 12163: Pre-existing Medical Comorbidity is not Associated With Neurological Outcomes in Comatose Survivors of Cardiac Arrest Undergoing Targeted Temperature Management
Authors: Nayeri Arash , Bhatia Nirmanmoh , Holmes Benjamin , Borges Nyal , Armstrong William , Young Michael , Wells Quinn , McPherson John
Published: April 2024

Introduction:
Evidence regarding the significance of pre-existing medical comorbidity in comatose survivors of cardiac arrest who undergo targeted temperature management (TTM) remains limited.

Hypothesis:
Increasing burden of medical comorbidity will predict poor neurological outcomes following TTM.

Methods:
We analyzed a prospectively collected cohort of 314 consecutive comatose survivors of cardiac arrest treated with TTM at a tertiary care hospital between 2007 and 2014. Overall burden of medical comorbidity was estimated with the use of the Charlson Comorbidity Index (CCI). Poor neurological outcome at hospital discharge, defined as a Cerebral Performance Category (CPC) score >2, was the primary outcome. Secondary outcomes included death prior to hospital discharge and at 1 year following cardiac arrest.

Results:
Amongst all patients, the median CCI score was 1 (IQR 0-3, range 0-11). A poor neurological outcome at hospital discharge was observed in 193 (61%) patients. One hundred and seventy-nine (57%) patients died prior to hospital discharge and a total of 195 (62%) patients had died at 1 year post-arrest. In multivariable logistic regression, elevated CCI scores were not associated with increased odds of poor neurological outcomes (OR 1.04, 95% CI 0.90-1.19, p=0.608) or death (OR 0.99, 95% CI 0.86-1.13, p=0.816) at hospital discharge. No association was seen between CCI scores and death at 1 year post-arrest (OR 1.09, 95% CI 0.95-1.26, p=0.220),
Table 1
.

Conclusions:
Increasing burden of medical comorbidity is not associated with neurological outcomes or survival in patients treated with TTM. Pre-existing comorbidity should not affect a patient’s candidacy for this treatment.

Table 1.
Adjusted odds ratios of poor neurological outcomes and death.

CCI, Charlson Comorbidity Index; CI, confidence interval; CPR, cardiopulmonary resuscitation; OR, odds ratio; ROSC, return of spontaneous circulation; TTM, targeted temperature management.
Abstract 12177: Plasma Volume Status Predicts Mortality in Heart Failure Patients
Authors: Sato Yu , Yoshihisa Akiomi , Watanabe Shunsuke , Yokokawa Tetsuro , Miura Shunsuke , Sato Takamasa , Abe Satoshi , Suzuki Satoshi , Oikawa Masayoshi , Kobayashi Atsushi , Yamaki Takayoshi , Kunii Hiroyuki , Saitoh Shu-ichi , Takeishi Yasuchika
Published: April 2024

Background:
The intravascular compartment is known as the plasma volume (PV). PV expansion plays an essential role in heart failure (HF), and large degrees of congestion relate to morbidity and mortality. Recently, it has been reported that PV is estimated by a simple formula based on hematocrit and body weight, not using radioisotope assays. We aimed to investigate the impact of PV status on prognosis of HF.

Methods and Results:
We calculated PV status as the following: Actual PV=(1-hematocrit)х[a+(bхbody weight)] (a=1530 in males and a=864 in females, b=41 in males and b=47.9 in females), Ideal PV=cхbody weight (c=39 in males and c=40 in females), and PV status=[(actual PV-ideal PV)/ideal PV]х100(%). We analyzed 1115 patients with HF who admitted to our hospital. These patients were divided into 3 groups based on the PV status: 1
st
(PV status<41.9%, n=371), 2
nd
(41.9%≤PV status<49.1%, n=372) and 3
rd
tertiles (49.1%≤PV status, n=372). In the multiple regression analysis to determine PV status, among considerable clinical variables, B-type natriuretic peptide (BNP), sodium and estimated glomerular filtration rate (eGFR) were predictors of PV status (BNP: ß=0.280, P<0.001; sodium: ß=-0.197, P<0.001; and eGFR: ß=-0.214, P<0.001). In the average follow-up of 1007 days, 287 deaths (149 cardiac deaths and 138 non-cardiac deaths) occurred. In the Kaplan-Meier analysis, all-cause mortality progressively increased from 1
st
to 2
nd
and 3
rd
groups (13.5%, 21.2% and 42.5%, P<0.001). In the Cox proportional hazard analysis, after adjusting for potential confounding factors including age, NYHA class, ejection fraction, BNP, sodium, eGFR, co-morbidities and medications, PV status was an independent predictor of all-cause mortality in HF patients (hazard ratio 1.420, 95% confidence interval 1.227-1.625, P<0.001).

Conclusion:
PV status, a marker of intravascular compartment and congestion, can identify high mortality in HF patients.
Abstract 12195: Carbohydrate and Protein but not Fat or Fiber Affects Glycemic Index and Glycemic Load Value Determinations
Authors: Meng Huicui , Matthan Nirupa R , Ausman Lynne M , Lichtenstein Alice H
Published: April 2024

Introduction:
Dietary glycemic index (GI) and glycemic load (GL) values have been calculated using data derived from instruments designed to estimate daily food intake. Since the absolute amount of carbohydrate (CHO) and combination of CHO with other macronutrients and fiber is highly variable among dietary patterns, the accuracy of these values is uncertain. This issue is of concern when dietary GI and GL values are used to identify diet/health outcome associations.

Hypothesis:
Increasing amounts of macronutrients (CHO, protein and fat) and fiber added to a test CHO challenge (50g available CHO) from white bread (WB) will alter GI and GL values.

Methods:
The trial included 4 studies, during which subjects (n=20-22, 50% female, 50-80y, BMI 25-30kg/m
2
, free from chronic disease and having fasting glucose levels ≤125mg/dL) received food challenges containing different amounts of the variable nutrient in a random order. In all studies, a glucose drink (50g available CHO/500mL) was used as the reference food. Studies 1-3 consisted of 4 food challenges, containing WB (50g available CHO+500mL water) alone or with additional CHO (12.5g, 25g, 50g), protein (12.5g, 25g, 50g) and fat (5.6g, 11.1g, 22.2g) from Rice Chex breakfast cereal (General Mills), tuna, and unsalted butter, respectively. Study 4 consisted of 3 food challenges, containing WB alone or with additional fiber (4.8g, 9.6g) from Cheerios (General Mills). Arterialized venous blood was sampled at 0, 15, 30, 45, 60, 90 and 120 minutes, and GI and GL values were calculated using the recommended incremental area under the curve (AUC) method.

Results:
Addition of 12.5g, 25g and 50g additional CHO to WB incrementally increased glucose AUC (p<0.0001), GI (p<0.0001) and GL (p<0.0001) values; while addition of protein (50g) to WB decreased glucose AUC (p=0.0026), GI (p=0.0139) and GL (p=0.0140) values. Addition of fat or fiber to WB had no significant effect on any measure.

Conclusions:
These data indicate that variability in postprandial GI and GL values is introduced when CHO containing foods are consumed in different amounts or in combination with protein. These conclusions raise the issue of whether GI and GL values from individual foods should be used to calculate dietary GI and GL values from dietary intake data.
Abstract 12196: ST2 Elevation in Myocardial Infarction - Associations With Cardiac Structure and Function
Authors: Jenkins William S , Roger Veronique L , Jaffe Allan S , Enriquez-Sarano Maurice
Published: April 2024

Introduction:
Soluble ST2 (sST2) is a serum marker of cardiomyocyte stress associated with a large risk of death and heart failure after myocardial infarction (MI). The relationship between sST2 and cardiac structure and function after MI however remains incompletely defined, and greater characterization is required prior to clinical application.

Methods:
Olmsted County, Minnesota residents who experienced their first MI between 2007 and 2012 were prospectively recruited. MIs were validated using standardized criteria and patients underwent simultaneous comprehensive Doppler echocardiography and sST2 measurement. The association between cardiac morphology and hemodynamics and sST2 were examined. Published normal values were used as referent ranges for sST2 levels.

Results:
Among 316 patients (mean age 65 [SD 14] years, 67% men, 32% ST-elevation MI), sST2 was measured 2.5 [SD 1.6] days after MI and within 0.7 [SD 2.3] days of echocardiography. Soluble ST2 was elevated in 33% of patients and univariately associated with decreased LV ejection fraction (LVEF), increased LV mass, impaired LV diastolic function and increased pulmonary artery pressure (ePAP) (Table).

After adjustment for age, sex, LVEF and key measures of LV filling pressures, elevated sST2 was independently associated with reduced LVEF (p=0.01) mitral valve deceleration time (p=0.03), greater left atrial volume (p=0.03) and mitral regurgitation (≥mild; p=0.09). LVEF and ePAP exhibited the strongest associations with elevated sST2 (both p<0.001).

Conclusions:
Soluble ST2 is frequently elevated following MI and is strongly associated with the morphologic and hemodynamic determinants of adverse LV remodeling that infer poor long-term outcome after MI.
Abstract 12209: Anticoagulation Use and Clinical Outcomes Following Major Bleeding on Dabigatran or Warfarin in Atrial Fibrillation
Authors: Hernandez Inmaculada , Zhang Yuting , Brooks Maria M , Chin Paul K , Saba Samir
Published: April 2024

Introduction:
Little is known about the patterns of anticoagulation use and clinical outcomes associated with the resumption of anticoagulation after a major hemorrhage.

Hypothesis:
We hypothesized that the discontinuation of anticoagulation would be associated with higher thromboembolic risk but lower risk of recurrent bleeding than the post-hemorrhage resumption of anticoagulation with warfarin or dabigatran.

Methods:
Using 2010-2012 Medicare Part D data, we identified atrial fibrillation patients who experienced a major bleeding while using warfarin (n=1135) or dabigatran (n=404) and categorized them by their post-hemorrhage use of anticoagulation. We followed them until a clinical event of ischemic stroke, recurrent hemorrhage, or death through December 31, 2012. We constructed logistic regression models to evaluate factors impacting anticoagulation resumption, and Cox Proportional Hazard models to compare the risk of ischemic stroke, all-cause mortality, and recurrent bleeding between treatment groups.

Results:
CHA2DS2-Vasc and HAS-BLED scores did not affect the odds of post-hemorrhage anticoagulation resumption. The odds of resuming anticoagulation decreased however by 11% (95%CI, 4%-18%) and 24% (95%CI, 9%-37%) for every 5 years increase in age for warfarin and dabigatran users, respectively. Resumption of anticoagulation with warfarin (hazard ratio (HR) 0.76; 95%CI, 0.59-0.97) or dabigatran (HR0.66; 95%CI 0.44-0.99) was associated with lower combined risk of ischemic stroke and all-cause mortality than anticoagulation discontinuation. The incidence of recurrent major bleeding was higher for patients who were prescribed warfarin after the bleeding event than for those prescribed dabigatran (HR2.31; 95%CI, 1.19-4.76) or whose anticoagulation ceased (HR1.56; 95%CI, 1.10-2.22), but did not differ between patients restarting dabigatran and those discontinuing anticoagulation.

Conclusions:
The benefit/risk ratio of dabigatran among atrial fibrillation patients who have survived a major hemorrhage is superior to that of warfarin and of anticoagulation discontinuation.
Abstract 12446: Comparison of Midterm Outcomes After Surgical Correction in Patients With Biventricular Obstruction Hypertrophic Cardiomyopathy
Authors: Zhai Shanshan , Fan Chaomei , Yan Jun , Wang Shuiyun , Song Yunhu , Yang Yinjian , Guo Xiying , An Shuoyan , Wang Zhimin , Duan Fujian , Zhao Shihua , Li Yishi
Published: April 2024

Introduction:
Data on the incidence, natural history and treatments of biventricular obstruction hypertrophic cardiomyopathy are limited.

Objective:
We aimed to the compare midterm outcomes of surgery and medication in biventricular outflow tract obstruction(BVOTO) HCM with left ventricular outflow tract obstruction (LVOTO) HCM and non-obstructive hypertrophic cardiomyopathy (NOHCM).

Methods:
Among 4945 HCM patients, we identified 43 with BVOTO and recruited age and sex matched 54 with LVOTO and 52 with NOHCM. The primary endpoint was all cause death and second endpoints were cardiovascular events.

Results:
Age and male were paired among BVOTO, LVOTO and NOHCM (26±17 ys, 30±18 ys, 31±16 ys P=0.3; 57%, 66%, 69%, p=0.5). More patients with BVOTO (69%) had NYHA III/IV than with LVOTO (51%)and NOHCM (15%) (p=0.000). And patients with BVOTO (5.6%±4 %) had higher risk of SCD than with LVOTO (3.9%±1.8%) and NOHCM (2.9%±2.1%)(p=0.000). In BVOTO, 20 patients had left-and-right sided correction (LRVC-B) (1 died and 5 had III AVB), 12 patients accepted left-sided correction (LVC-B) (1 died and 1 occurred III AVB) while 11 patients received medication. At the last follow-up, patients in LRVC-B and LVC-B had a reduction in left and right ventricular intracavity pressure gradient and NYHA class (vs before myectomy, p < 0.001). And no death occurred in the remained 147 patients. The second endpoint-free survival rates of BVOTO were less than LVOTO and NOHCM while the rates were similar among LRVC-B, LVC-B, LVC-L and NOHCM groups. (Fig1ab) Independent predictors of the second endpoint were age (HR 1.05,95%CI 1.0-1.1), RVOTO (HR 1.06,95%CI 1.03-1.10), myectomy (HR 0.16,95%CI 0.03-0.61) and pre-NYHA (HR 4.1,95%CI 2.1-8.33).

Conclusions:
Patients with BVOTO had more severe symptoms. Both LRVC-B and LVC-B could improve symptom but LRVC-B had a higher risk of III AVB. Mid-term outcomes after surgical correction in BVOTO were similar to that in NOHCM.
Abstract 12447: Early Coronary Reperfusion Improves Cerebral and Systemic Hemodynamics After Ischemic Refractory Cardiac Arrest and Extracorporeal Resuscitation in Pigs
Authors: Hutin Alice , Lamhaut Lionel , Lidouren Fanny , Kohlhauer Matthias , Mongardon Nicolas , Carli Pierre , Berdeaux Alain , Ghaleh Bijan , Tissier Renaud
Published: April 2024

Introduction:
Extracorporeal cardiopulmonary resuscitation (ECPR) is widely proposed for the treatment of refractory cardiac arrest. It should be associated to etiologic determination, especially if acute coronary artery occlusion is suspected. However, prioritization of care remains unclear in this situation.

Hypothesis:
Our goal was to determine whether reperfusion should be instituted as soon as possible during ischemic refractory cardiac arrest treated by extracorporeal cardiopulmonary resuscitation (ECPR) in pigs.

Methods:
Pigs were instrumented and submitted to coronary artery occlusion prior to ventricular fibrillation. After 5 min of untreated cardiac arrest, life support was started using external chest compression (ECC) during 15 min followed by ECPR during 240 min, respectively. Animals randomly underwent either early or late coronary reperfusion after 20 or 120 min of ECPR, respectively. Return of spontaneous circulation (ROSC) was determined as organized ECG rhythm with systolic blood pressure above 80 mmHg.

Results:
Hemodynamic parameters were not different between groups at baseline or during ECC. Since the onset of ECPR, carotid blood flow was improved by ≈70% vs ECC in both groups. No animal (0/7) elicited ROSC after late reperfusion vs 4/7 after early reperfusion (p<0.05). Hemodynamic parameters, such as mean arterial pressure and carotid blood flow, were improved in early vs late reperfusion groups (Figure), along with infarct size decrease (71±4 vs 84±2 % of the risk zone, respectively; p<0.05).

Conclusions:
Early reperfusion improved hemodynamic status and increased ROSC chances after ischemic refractory cardiac arrest treated by ECPR. This supports the need of rapid reperfusion in this situation.

Figure:
Carotid blood flow after extracorporeal cardiopulmonary resuscitation (ECPR) and successful defibrillation (*, p<0.05 between groups; comparisons were only made at the end of the follow-up).
Abstract 12458: Mineralocorticoid Receptor Antagonist Use in Patients With Heart Failure and Co-Morbid Diabetes or Chronic Kidney Disease
Authors: Cooper Lauren B , Lippmann Steven J , Greiner Melissa A , Kelly Jacob P , Sharma Abhinav , Fonarow Gregg C , Yancy Clyde W , Heidenreich Paul A , Hernandez Adrian F
Published: April 2024

Introduction:
The risk of hyperkalemia or acute renal insufficiency (ARI) may limit the use of mineralocorticoid receptor antagonists (MRAs) in heart failure (HF) patients, especially in those with diabetes mellitus (DM) or chronic kidney disease (CKD).

Hypothesis:
Despite risks, MRAs may be beneficial in these patients.

Methods:
Using the GWTG-HF registry linked to Medicare claims, we analyzed patients hospitalized from 2005-2013 with a history of DM or CKD and not on a MRA at admission. Patients were stratified by MRA use at discharge. We used proportional hazards models, weighted by inverse treatment probability, for associations between MRA use and 30-day, 1- and 3-year mortality, all-cause readmissions, and readmission for HF, hyperkalemia, or ARI. We performed interaction analyses for differential effects on 3-year outcomes for reduced and preserved ejection fraction (HFrEF and HFpEF).

Results:
Of 16,848 patients, 12.3% received a MRA at discharge. Higher creatinine was associated with lower odds of MRA use (OR 0.66, 95% CI 0.61, 0.71) but higher potassium was not (OR 1.00, 95% CI 0.90, 1.11). There was no difference in risk of mortality between groups (Table). MRA use was associated with increased short- and long-term risk of hyperkalemia and ARI, but decreased risk of 1- and 3- year all-cause rehospitalization. In the interaction analysis, HFpEF patients on MRA had increased rehospitalization for hyperkalemia (HR 1.44, 95% CI 1.17, 1.78) and ARI (HR 1.29, 95% CI 1.15, 1.44), but HFrEF patients did not (hyperkalemia HR 1.04, 95% CI 0.86, 1.25; ARI HR 0.94, 95% CI 0.82, 1.07). There were no significant interactions by EF group for mortality, or all-cause or HF readmission.

Conclusions:
Among patients with HF and DM or CKD, MRA use was associated with less all-cause hospitalizations despite increased risk of hyperkalemia and ARI. The increased risk of adverse events was confined to patients with HFpEF. MRAs may be safe in a highly selected group of HF patients with DM or CKD.
Abstract 12470: Carotid Intima-Media Thickness and Risk of Sudden Cardiac Death: The Atherosclerosis Risk In Communities (ARIC) Study
Authors: Suzuki Takeki , Wang Wanmei , Wilsdon Anthony , Butler Kenneth R , Adabag Selcuk , Griswold Michael E , Nambi Vijay , Rosamond Wayne , Sotoodehnia Nona , Mosley Thomas H
Published: April 2024

Introduction:
Sudden cardiac death (SCD) has been a public health issue worldwide. Carotid intima-media thickness (C-IMT) is a known surrogate marker for atherosclerosis. Whether subclinical atherosclerosis is associated with risk of SCD remains unknown especially in a middle-aged general population.

Methods:
We investigated the associations of C-IMT with SCD through 2012 among 15,307 blacks and whites participants at the first visit (1987-1989) of the community based-ARIC study. C-IMT (mean and maximum of C-IMT and common carotid artery (CCA)-IMT) was measured at the first visit by ultrasound. Presence of plaque was judged by trained readers and defined as two of the following three criteria: abnormal wall thickness (defined as C-IMT >1.5 mm), abnormal shape (protrusion into the lumen and loss of alignment with adjacent arterial wall boundary), and abnormal wall texture (brighter echoes than adjacent boundaries). Kaplan-Meier curves and Cox proportional hazards models were used to evaluate associations of incident SCD with baseline C-IMT.

Results:
Over a median of 23.48 years of follow-up, 569 participants had SCD (37 cases per 1,000 person-years). C-IMT was associated with risk of SCD after adjustment for traditional risk factors (Figure and Table). Presence of plaque was associated with risk of SCD (HR 1.55; 95% CI 1.28-1.86,
P
<0.001).

Conclusion:
Subclinical atherosclerosis measured by C-IMT was associated with risk of SCD in a middle-aged general population. These results may suggest importance of subclinical atherosclerosis in SCD risk and lead to early therapeutic intervention to prevent SCD.
Abstract 12514: Myocardial Glucose Metabolism Evaluated by Fasting 18Fluorodeoxyglucose-Positron Emission Tomography in Pulmonary Hypertension
Authors: Nakamura Tomohisa , Tahara Nobuhiro , Sugiyama Youichi , Bekki Munehisa , Tahara Atsuko , Honda Akihiro , Kumagai Eita , Igata Sachiyo , Fukumoto Yoshihiro
Published: April 2024

Background:
The myocardium changes its energy substrate from fatty acid oxidation to glycolysis under increased afterload. 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) can provide clinical information about myocardial glucose metabolism.

Purpose:
We aimed to investigate the myocardial glucose metabolism in patients with pulmonary hypertension (PH).

Methods:
We studied 45 patients with pre-capillary PH (36 females; mean age 54 ± 16 years), who underwent magnetic resonance imaging and FDG-PET. FDG uptake in the right ventricle (RV) and left ventricle (LV) was measured by maximum standardized uptake values (SUV). Further, we examined whether pulmonary vasodilators could shift the myocardial glucose metabolism in 30 patients.

Results:
The ratio of FDG uptake between RV to LV (SUV
R/L
) and mean pulmonary arterial pressure (mPAP) were 0.84±0.08 and 39.2±1.7 mmHg, respectively. Multiple stepwise regression analysis revealed that mPAP was independently associated with SUV
R/L
(R
2
=0.396). The SUV
R/L
was significantly decreased from 0.88±0.41 to 0.70±0.29 (
p
<0.05) by treatment with pulmonary vasodilators. The increases in RV ejection fraction and 6-min walk distance were independently associated with the decrease in SUV
R/L
after treatment (R
2
=0.466).

Conclusions:
The present study reveals that SUV
R/L
is associated with disease severity of PH, suggesting that myocardial glucose metabolism may contribute to its clinical importance of patient care.
Abstract 12529: The Association of the Different Vitamin D Metabolites to Death, Myocardial Infarction, Heart Failure, and Stroke: Results From the Intermountain Heart Collaborative Study
Authors: May Heidi T , Galenko Oxana , Carlquist John F , Weaver Lindell K , Knight Stacey , Barker Tyler , Knowlton Kirk U , Muhlestein Joseph B
Published: April 2024

Introduction:
Many epidemiological studies have shown that total circulating levels of 25-hydroxyvitamin D (VitD) are strongly associated with poor cardiovascular (CV) outcomes. However, 85-90% of circulating VitD is bound to vitamin D binding protein (BP) or albumin, and levels obtained may not be truly reflective of the VitD available to act on target cells. Whether more direct markers of VitD activity such as bioavailable VitD (BIO) or free VitD (FREE) are more effective in predicting future CV risk is not known.

Hypothesis:
The more direct markers of VitD activity are more strongly associated with adverse CV outcomes.

Methods:
Patients (N=4285) undergoing angiography for CAD determination were studied. Levels of VitD, BP and albumin were directly measured and BIO and FREE were calculated using standard formulae. Multivariable Cox hazard regression was utilized to determine quartile (Q) associations with death (all-cause, CAD, and cardiac), MI, HF hospitalization, and stroke. Median length of follow-up was 10.9 years.

Results:
Patients averaged 64±12 years, 66% male, 23% diabetic, 90% Caucasian, and 70% diagnosed with CAD. Median and interquartile ranges of VitD, BP, BIO, and FREE were 24.9 (20.0, 28.7) ng/mL, 168.3 (103.7, 245.9) ug/mL, 7.1 (3.9, 15.2) ng/mL, and 15.7 (9.2, 33.3) pg/mL, respectively. Multivariable hazard ratios for the various metabolites with each of the outcomes are shown in Table. BP was not associated with any of the outcomes. VitD, BIO, and FREE were all associated with death (all-cause, CAD, and cardiac). VitD continued to be significantly associated with HF hospitalization and stroke, with its association to MI being attenuated.

Conclusion:
Among this predominately Caucasian population, VitD was found to consistently be the strongest predictor of all of the outcomes over BP, BIO, and FREE. Future studies are needed to evaluate whether obtaining thresholds of VitD levels are associated with a reduction in CV risk.
Abstract 12563: Anatomical Situation Surrounding the Esophagus Affects the Prevalence of Transmural Thermal Injury After Pulmonary Vein Isolation
Authors: Kaneshiro Takashi , Suzuki Hitoshi , Matsumoto Yoshiyuki , Nodera Minoru , Kamioka Masashi , Kamiyama Yoshiyuki , Yoshihisa Akiomi , Takeishi Yasuchika
Published: April 2024

Introduction:
Transmural thermal injury (TTI), such as esophageal erythema and periesophageal nerve injury leading to gastric hypomotility, is an important complication associated with pulmonary vein isolation (PVI). Esophagus is surrounded with a small distance by left atrium (LA) posterior wall, descending aorta and left inferior PV (LIPV) in infero-posterior portion of LA. However, the predictor of this complication associated with anatomical situation among these structures has not been fully established.

Methods:
The consecutive 133 patients (61±9 years, 111 men) who underwent PVI for drug refractory atrial fibrillation and gastrointestinal endoscopy on the day following PVI were investigated. With echocardiography data, LA dimension and LA volume index in each patient were measured. We measured the angle of LA posterior wall to descending aorta (LA-Ao angle), the branching angle of LIPV to coronal plane (LIPV angle), and the minimum distance between descending aorta and LA posterior wall sandwiching esophagus with computed tomography. The relationships of TTI with clinical and anatomical parameters were examined.

Results:
All patients had left-sided or central location of esophagus, which overlay the posterior ablation line of left PV. Radiofrequency energy was delivered with a maximum output of 20 watts, and contact force was maintained between 10-20 g in left posterior ablation line. TTIs were occurred in 24 patients after PVI (erythema in 5 and gastric hypomotility in 19). The parameters including age, gender, body mass index, LA diameter and LA volume index in echocardiography were not associated with the prevalence of TTI. However, LIPV angle was larger (33.2±13.6 ° vs. 20.7±10.2 °, P< 0.0001) and LA-Ao distance was shorter (4.3±1.4 mm vs. 6.2±2.4 mm, P= 0.0002) in TTI (+) group compared to TTI (-) group. LA-Ao angle tended to be smaller in TTI (+) group (25±10 degrees vs. 29±10 degrees, P= 0.08), and was significantly correlated with LA-Ao distance (R= 0.321, P= 0.0002).

Conclusion:
The anatomical proximity of LA posterior wall, LIPV and descending aorta surrounding esophagus is strongly associated with the prevalence of TTI.
Abstract 12588: Invasive Therapies Reduce Cardiovascular Death but Not Sudden Cardiac Death in Obstructive Hypertrophic Cardiomyopathy
Authors: An Shuo-yan , Yang Yin-jian , Fan Chao-Mei , Qiao Shu-bin , Wang Shui-yun , Song Yun-hu , Yuan Jian-song , You Shi-jie , Guo Xi-ying , Zhai Shan-shan , Wang Zhi-min , Duan Fu-jian , Zhang Xiu-ling , Zhao Xing , Wang Fengqi , Zhu Hongguang , Lin Aiqing , Wu Xia , Li Yi-shi
Published: April 2024

Background:
Data on survival after medical therapy, alcohol septal ablation (ASA) and myectomy of Asian patients with obstructive hypertrophic cardiomyopathy (HCM) were lacking. Besides, long-term effects of ASA and myectomy, especially on sudden cardiac death were controvertial.

Hypothesis:
We assessed the hypothesis that patients with obstructive HCM who were treated with invasive therapy had a favorable survival, similar to that of patients with non-obstructive HCM.

Methods:
This study included 1,065 consecutive patients with HCM (mean age 48±13 years, 64.3% male ) from 4 centers. A total of 750 patients (70.4%) had left ventricular outflow tract gradients ≥ 50 mm Hg, of whom 254 (23.8%) were treated medically, 236 (22.2%) underwent ASA, and 260 (24.4%) underwent myectomy. Primary endpoints were and aborted cardiac arrest.

Results:
The mean follow-up period was 5.5±3.7 years. The 5- and 10-year endpoint-free survival rates were similar among ASA patients(94.6% and 93.6%), myectomy patients (93.8% and 91.2%), and non-obstructive patients (95.6% and 93.4%), and better than that of medical therapy (85.9%, and 81.6%; log-rank p =0.004, = 0.025 and <0.001, respectively). The incidence of sudden cardiac death was similar among the ASA group (2.2%), myectomy group (1.6%), medically treated group (3.5%) and non-obstructive HCM (1.6%) (P=0.53). For the total study population, independent determinants of the endpoints were female (HR: 1.65, 95% CI: 1.03-2.66, P=0.037), unexplained syncope (HR: 1.70, 95% CI: 1.07-2.71, P=0.026), and left atrial diameter (HR: 1.06, 95% CI: 1.03-1.10, P<0.001). For the obstructive HCM patients, invasive therapy (HR: 0.50, 95% CI: 0.29-0.88, P=0.016), female (HR: 1.82, 95% CI:1.06-3.12, P=0.03) and left atrial diameter (HR: 1.05, 95% CI: 1.01-1.09, P=0.01) were independently associated with primary endpoints.

Conclusions:
ASA and myectomy in patients with obstructive HCM have a low incidence of cardiovascular death, similar to that of patients with non-obstructive HCM. But sudden cardiac death was not improved after invasive therapies.
Abstract 12613: High-sensitivity Troponin-I is Predictive of Incident Atrial Fibrillation in a High-Risk Patient Population
Authors: Schultz William , Hayek Salim , Ko Yi-An , Lisko John , Awad Mosaab , Hosny Kareem , Ahmed Hina , Patel Keyur , Yuan Michael , Hartsfield Joy , Gray Brandon , Bhimani Ravilla , Kim Jonathan , Shaw Leslee , Wilson Peter , Vaccarino Viola , Quyyumi Arshed
Published: April 2024

Introduction:
Biomarkers have been linked to incident atrial fibrillation (AF) in the general population. We evaluated the association between several biomarkers previously shown to be predictors of death and myocardial infarction (MI), and development of AF in a high-risk patient population with CAD.

Hypothesis:
Biomarkers will predict new-onset AF in a population with CAD.

Methods:
2773 patients (age 62±13 years) with known or suspected CAD were enrolled in the Emory Cardiovascular Biobank. Circulating levels of high-sensitivity troponin I (hs-TnI), fibrin degradation products (FDP), c-reactive protein (CRP), soluble urokinase-type plasminogen activator receptor (suPAR), and heat shock protein 70 (HSP70) were measured with ELISA. Biomakers were dichotomized into high or low levels by median, as well as into quartiles. Cox proportional hazard models were used to investigate the associations between biomarkers and incident AF after adjustment for age, sex, race, body mass index (BMI), smoking history, hypertension, diabetes, hyperlipidemia, history of MI, CAD severity by Gensini score, estimated glomerular filtration rate, and use of ACE inhibitors/ARBs/statins.

Results:
During a median 5.75 years of follow-up, 423 (15.3%) patients developed AF. Subjects with incident AF were older, had higher BMI, greater CAD severity, lower eGFR, and more often had prior MI. Elevated levels of hs-TnI (≥median 4.7 pg/mL) were associated with incident AF (hazard ratio (HR) 2.00, [95% confidence interval (CI) 1.60-2.51], P<0.001), that remained significant after adjustment for the aforementioned covariates (HR 1.75, 95%CI 1.33-2.31, P<0.0001). The findings were supported by quartile analysis when comparing the first quartile to the fourth quartile (HR 1.82, 95% CI 1.23-2.70, p=0.003 after adjustment). FDP, suPAR, CRP, and HSP70 were not associated with incident AF after adjustment for covariates.

Conclusions:
In subjects with CAD, higher hs-TnI levels are associated with incident AF even after adjustment for severity of CHD. Risk stratification for incident AF may permit institution of more aggressive risk factor modification and targeted screening.
Abstract 12625: Splenic Leukocytes Defines the Resolution of Inflammation and Left Ventricle Healing in Heart Failure Pathology
Authors: Halade Ganesh V , Vlasakov Iliyan , Kain Vasundhara , Norris Paul , Serhan Charles N , Ingle Kevin A
Published: April 2024

Introduction:
After myocardial infarction (MI) self-healing is prominent in mice but not in humans. MI-induced innate inflammatory and resolving response is unclear in left ventricle (LV) healing.

Hypothesis:
To define innate and resolving response, our aim was to quantitate time-dependent generation of specialized pro-resolving mediators (SPMs) and leukocyte trafficking in the LV and spleen post-MI.

Methods:
We determined the leukocyte kinetics by flow cytometry and quantitated resolution metabolome using mass spectrometry in C57BL/6 mice after permanent coronary ligation.

Results:
Lipid Mediator metabololipidomic analyses revealed that spleen not only serves as a leukocyte reservoir but it also participates actively in SPMs production post-MI. Post-MI leukocyte (CD11b
+
Ly6G
+
CD206
+
) turnover at d1 linked to increased SPMs levels in the infarcted LV with marked increase of resolvin (Rv)D1, RvD3-6, maresin (MaR)1, lipoxins (LX) and protectin D1 compared to d0 naïve controls and d5 post-MI. Before MI, SPMs such as RvD5, RvD6, protectin (PD)1, AT-PD1, MaR1, LXA
4
, AT-LXA
4
, AT-LXB
4
, were higher in spleen than LV indicating that splenic leukocytes mobilize SPMs to activate the healing program in LV post-MI. Lipoxygenase (LOX -5, -12 and -15) were preferentially activated in LV, while cyclooxygenase (COX-1 and -2) in the spleen post-MI. MI-induced comprehensive leukocyte analyses provided the self-regulating means of pro-inflammatory and resolving neutrophils (CD11b
+
Ly6G
+
CD206
+
) and macrophages (CD11b
+
Ly6C
hi
CD206
+
) in a time dependent manner in the infarcted LV but to a lesser extent in the spleen. Thus, the splenic storage of SPMs, generation of increase LOX-mediated SPMs in the infarcted LV and COX-mediated prostanoids in the spleen facilitates the MI-induced murine LV healing post-MI.

Conclusions:
The abundance of SPMs in the spleen before MI and amplified SPMs generation in the infarcted LV within 24 hours post-MI confirms that splenic leukocytes determine the murine self-healing post-MI. Thus, the acute phase coincides with the resolving response post-MI and demands investigation of the SPMs role in heart failure pathology.
Abstract 12626: Co-Injection of Induced Pluripotent Stem Cell-Derived Endothelial Cells With Shear Thinning Hydrogel Enhances Survival and Angiogenesis in a Murine Model of Peripheral Arterial Disease
Authors: Huang Ngan F , Cai Lei , Dewi Ruby , Strassberg Zachary , Foster Abbygail , Hou Luqia , Heilshorn Sarah C
Published: April 2024

Introduction:
Human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) are a promising cell source for enhancing blood perfusion for treatment of peripheral arterial disease (PAD). However, poor cell survival is a critical bottleneck to the efficacy of stem cell therapy.

Hypothesis:
We hypothesize that encapsulation of cells within an injectable shear-thinning hydrogel with controllable properties will prolong cell survival under ischemic conditions and maintain cellular phenotype, in comparison to cell injection in saline.

Methods:
The protein hydrogel is comprised of two complementary engineered proteins that self-assemble upon simple mixing. The hydrogel network incorporates a polyethylene glycol physical crosslinker that modulates hydrogel stiffness and degradation. Bioluminescent iPSC-ECs were encapsulated within the hydrogel with controllable stiffness (
G’
~10-800 Pa) under conditions of hypoxia (1% O
2
). The cells within hydrogel were then subjected to an
in vitro
model of injection and assayed for cell survival, proliferation, and endothelial phenotype for up to 14 days. To verify these results in an experimental model of PAD, 10
6
cells were injected in saline or in 400 Pa hydrogel into the ischemic limb of SCID mice for assessment of cell viability and blood flow recovery.

Results:
Acutely after injection
in vitro
, cell survival in saline was 65%, in comparison to 94% in hydrogels with stiffnesses of 10-800 Pa. Bioluminescence imaging demonstrated the highest cell proliferation in the hydrogel with 400 Pa stiffness after 14 days. In the 400 Pa hydrogel, iPSC-ECs maintained elongated morphology with robust expression of endothelial phenotypic marker, CD31. In the ischemic hindlimb, iPSC-EC retention was markedly increased when encapsulated in the 400 Pa hydrogel, compared to saline delivery. Concomitantly, mean blood perfusion recovery in the ischemic limb after 14 days was 0.68 when treated with cells in hydrogel, in contrast to 0.61 when cells were injected in saline.

Conclusions:
These findings demonstrate that stem cell encapsulation within the 400 Pa protein hydrogel improves cell viability and blood perfusion, which may have therapeutic benefit for treatment of PAD.
Abstract 12646: Cellular Mechanisms Underlying Post-operative Atrial Fibrillation in Patients
Authors: Khan Azinwi P , Voigt Niels , Heijman Jordi , Ravens Ursula , Nattel Stanley , Dobrev Dobromir
Published: April 2024

Background:
Post-operative atrial fibrillation (poAF) after cardiac surgery is a common condition. Although usually self-limiting, poAF increases length of hospital stay and can cause debilitating strokes. A multifactorial pathophysiology involving triggered activity has been hypothesized, but the underlying cellular and molecular mechanisms are unknown and were the subject of this study.

Methods:
Multicellular action potentials (APs) were recorded with sharp microelectrodes in right atrial trabeculae obtained from sinus-rhythm patients during open-heart surgery and correlated with subsequent non-poAF (Ctl) or poAF status. Membrane currents (whole-cell voltage clamp) and [Ca
2+
]
i
(Fluo-3) were also measured in right atrial cardiomyocytes isolated from Ctl and poAF patient samples. Protein expression was quantified by immunoblot.

Results:
In poAF, AP duration at 90% repolarization (APD
90
)

was slightly prolonged (Fig A), whereas AP amplitude, upstroke velocity, APD
20
, APD
50,
and resting membrane potential (RMP) were unchanged. I
Ca,L
-triggered [Ca
2+
]
i
transient (CaT) amplitude was 37% lower in poAF despite greater Ca
2+
influx via L-type Ca
2+
current (integral I
Ca,L
), pointing to sarcoplasmic reticulum (SR) dysfunction (Fig B). Na
+
-Ca
2+
exchange (NCX) activity was similar in both groups (Fig C). SR Ca
2+
content calculated by integrating NCX current (I
NCX
) during caffeine-induced SR Ca
2+
release was decreased by 50% in poAF (Fig C), likely because of smaller expression of SR Ca
2+
-ATPase-2a (SERCA2a) and decreased Ser16-phosphorylation (stronger SERCA2a inhibition) of the SERCA2a regulator phospholamban (PLB, Fig D). Expression of cardiac SR ryanodine receptor (RyR2) was reduced by 56% (Fig D), consistent with the reduced CaT amplitude.

Conclusions:
PoAF is associated with prolonged APD and impaired SR function. These abnormalities likely result in the Ca
2+
mishandling that predisposes patients to triggered activity underlying poAF.
Abstract 12661: Respiratory Muscle Weakness is an Independent Determinant for Decreased Parasympathetic Activity in Patients With Chronic Heart Failure
Authors: Hamazaki Nobuaki , Masuda Takashi , Kamiya Kentaro , Matsuzawa Ryota , Nozaki Kohei , Tanaka Shinya , Kamada Yumi , Yabu Kanae , Nakamura Takeshi , Tabata Minoru , Maekawa Emi , Noda Chiharu , Yamaoka-Tojo Minako , Ako Junya
Published: April 2024

Background:
Decreased parasympathetic activity and respiratory muscle weakness are known as indicators for poor outcome in patients with chronic heart failure (CHF). Although the effect of respiratory modulation on autonomic system has been documented, the relationship between respiratory muscle strength and parasympathetic activity is still unknown. The present study aimed to investigate the influence of respiratory muscle weakness on parasympathetic activity in CHF patients.

Methods:
We studied 254 patients with compensated CHF (60.3±12.0 years, 202 males) who received cardiac rehabilitation during hospitalization and after hospital discharge. Maximal inspiratory pressure (PI
max
) was measured as a respiratory muscle strength using a spirometer 2 months after the discharge. Patients received symptom limited cardiopulmonary exercise test (CPX) and then heart rate recovery (HRR) during the first minute after the cessation of CPX was assessed as a parasympathetic activity. HRR of ≤18 /min was determined as a decreased parasympathetic activity. Patients were divided into three groups based on the tertile of PI
max
: low PI
max
(PI
max
<58.7 cmH
2
O), moderate PI
max
(58.7≤ PI
max
<83.6 cmH
2
O) and high PI
max
(PI
max
≥83.6 cmH
2
O) groups. We compared the HRR among the three groups and identified the determinant for HRR of ≤18 /min using a multivariate logistic regression analysis.

Results:
Ninety-four patients among the studied patients, 47 in the low PI
max
group, 28 in the moderate PI
max
group and 19 in the high PI
max
group, showed HRR of ≤18 /min. The low PI
max
group showed significantly lower HRR as compared with the other two groups (P=0.001 and <0.001, respectively). The multivariate logistic regression analysis identified the PI
max
as a significant independent determinant for HRR of ≤18 /min (odds ratio=0.832, P=0.008, Figure).

Conclusion:
Respiratory muscle weakness was an independent determinant for decreased parasympathetic activity in patients with CHF.
Abstract 12671: Left Atrial Volumes Corrected for Heart Size are Superior Echocardiographic Measures for Diagnosing Paroxysmal Atrial Fibrillation in Ischemic Stroke and Transient Ischemic Attack Patients
Authors: Skaarup Kristoffer G , Christensen Hanne , Høst Nis , Mahmoud Masti M , Ovesen Christian , Olsen Flemming J , Biering-Sørensen Tor
Published: April 2024

Introduction:
The underlying cause of ischemic strokes (IS) and transient ischemic attacks (TIA) is not identified in 25% of the cases. However, asymptomatic paroxysmal atrial fibrillation (PAF) is often assumed to be the cause of the cryptogenic IS or TIA

Hypothesis:
The aim of this study was to examine if echocardiographic measures of LA volume (LAV) corrected for the left ventricular (LV) length (LAVMax/Min/LV length) could predict PAF in patients with IS and TIA.

Methods:
We retrospectively included 218 patients who after acute IS or TIA underwent a transthoracic echocardiographic examination in sinus rhythm. Patients were designated as PAF-patients if they had one or more reported incidents of AF before or after their echocardiographic examination.

Results:
Patients in the PAF group were significantly older (62±13 vs. 52±14 years, p<0.001), had higher CHA2DS2-VASc score (3.3±1.3 vs. 3.8±1.3, p=0.042) and higher National Institutes of Health Stroke Scale (NIHSS) score (2.9±4.9 vs. 1.4±3.3, p=0.016) than patients without PAF. Besides these, no other baseline characteristics (sex, hypertension, diabetes, cholesterol) were associated with PAF. None of the conventional echocardiographic parameters (LV ejection fraction, LV volumes, E/A-ratio, E-wave deceleration time, LAVmax) were significantly associated with PAF. However, the atrial measures corrected for LV length (LAVMax/LV length and LAVMin/LV length) were significantly higher (LAVMax/LV length: 7.6±3.3 mL/cm vs. 6.5± 2.0 mL/cm, p=0.009; LAVMin/LV length: 3.7± 2.1 mL/cm vs. 2.8±1.1 mL/cm, p<0.001) in patients with PAF (Figure), even after adjustment for age, gender, CHA2DS2-VASc and NIHSS scores.

Conclusion:
In patients with IS and TIA, measures of LA size corrected for LV length are independently associated with the presence of PAF. Applying these may yield better risk stratification for PAF-presence in patients suffering cryptogenic IS and TIA.