bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12679: Circulating High-Density Lipoprotein Particle Profiles Are Independently Associated With Heart Failure With Preserved Ejection Fraction and Predict Adverse Clinical Outcomes
Authors: Hunter Wynn G , McGarrah Robert W , Kelly Jacob P , Haynes Carol , Craig Damian M , Velazquez Eric J , Kraus William E , Shah Svati H
Published: April 2024

Introduction:
High-density lipoprotein particle concentration (HDL-P) and size (HDL-Sz) impact atherogenesis and inflammation, both of which are implicated in the pathobiology of heart failure with preserved ejection fraction (HFpEF). However, the role of HDL in HFpEF has not been well evaluated. We characterized HDL particle characteristics in a large cardiovascular cohort to determine association with HFpEF and prognostic capability in this growing patient population.

Methods:
HFpEF cases (N=1004), HFrEF controls (N=782), and No-HF controls (N=4742) were identified in the CATHGEN biorepository of sequential patients undergoing cardiac catheterization. HFpEF was defined by left ventricular EF (LVEF) ≥45% and history of HF; HFrEF was defined similarly, except for LVEF <45%; No-HF had LVEF ≥45%, and no history of HF. NMR-based lipoprotein profiling was performed on frozen fasting plasma obtained at catheterization. Multivariable analysis of variance was used to compare HDL profiles among groups; proportional hazards modeling evaluated associations among HDL profiles and time-to all-cause mortality and major adverse cardiac events.

Results:
HDL-Sz, large HDL-P, and small HDL-P differed significantly across groups (all
P
≤0.006). Mean HDL-Sz was higher in HFrEF than HFpEF, both of which were higher than No-HF (all two-way
P
<0.0001
)
. Large HDL-P was greater in HFrEF than HFpEF (
P
=0.007); by contrast, small HDL-P was lower in HFrEF than HFpEF, which were both lower than No-HF (all
P
≤0.0002). Greater HDL-Sz and large HDL-P were associated with increased risk of adverse events; whereas, greater small HDL-P was associated with decreased risk (Table).

Conclusions:
In the largest analysis of HDL profiles in HFpEF, we identified derangements in HDL-P and HDL-Sz independently associated with adverse events. These findings suggest that HDL profiling may be helpful in identifying high-risk HFpEF subtypes, and could provide new insights into HFpEF pathophysiology.
Abstract 12681: Secretory Factor(s) Derived From Human Pulmonary Artery Endothelial Cells Induce Pseudo-hypoxic Activation of HIF-1α Signaling and Metabolic Reprogramming in Human Pulmonary Artery Smooth Muscle Cells
Authors: Xiao Wusheng , Oldham William , Loscalzo Joseph
Published: April 2024

Cell-cell communication is required for maintaining physiological functions of the vasculature, and is also involved in the development of vascular disorders, including pulmonary arterial hypertension. Yet, how heterologous cell-cell crosstalk influences cellular metabolism in pulmonary vascular cells is not well understood.

Objective:
We studied how the interaction of heterologous pulmonary vascular cells regulates vascular metabolism.

Methods and Results:
Human pulmonary artery endothelial cells (PAEC) and smooth muscle cells (PASMC) were cultured in a transwell coculture system with or without conditioned medium (CM) under ambient oxygen levels. Results from the Seahorse XF24 analyzer showed an increase in extracellular acidification rate (indicative of glycolysis), and a decrease in oxygen consumption rate (indicative of mitochondrial respiration) in PASMC cultured in CM from PAEC, suggesting a metabolic shift toward glycolysis induced by an endothelial product. This metabolic shift correlated with activation of HIF-1α signaling, as demonstrated by normoxic stabilization of HIF-1α protein and upregulation of its target gene expression (
GLUT1
,
HK2
, and
PDK1
) in PASMC. Interestingly, these effects were not observed in PAEC cultured with PASMC or in CM from PASMC. We also found that HIF-1α stabilization is independent of its transcription and of the protein levels of prolyl hydroxylase domain protein 2 (PHD2) and pVHL; however, PHD activity decreased in PASMC cultured in CM from PAEC, suggesting that factor(s) secreted by PAEC could suppress PHD activity in PASMC. To identify the potential factor(s), CM from PAEC were pretreated by heat inactivation or with proteinase K and fractionated by filtration column. Results from these experiments suggested that the inhibitor(s) is(are) a small molecule (<10 kDa). We then tested known PHD inhibitors and found that pyruvate, succinate, fumarate, lactate, glutamate, and reactive oxygen species were unlikely to be the mediators. Overall, our study indicates that cellular metabolism of PASMC can be reprogrammed by PAEC through a paracrine mechanism. These results may provide novel insights into mechanisms of vascular cell-cell crosstalk and its consequences for vascular metabolism and disease.
Abstract 12714: Prevalence and Risk Factors of Peripheral Vascular Disease in Rural India: A cross Sectional Study
Authors: Tummala Ramyashree , Banerjee Kinjal , Mahajan Kapil , Gupta Anjan
Published: April 2024

Background:
Peripheral vascular disease (PVD) is a major cause of morbidity and mortality especially affecting the elderly. PVD is largely undetected due to its silent progression. Ankle brachial index (ABI) is a symptom independent reliable screening tool for PVD in primary care, but remains underused. Our aim was to estimate the burden of PVD in this region and correlate it to various risk factors both quantitatively and qualitatively.

Materials and Methods:
From an outpatient medical camp in rural India, 100 patients were recruited randomly. They were assessed for symptoms, medical history and risk factor screening that included 11 well known risk factors using a pre formatted questionnaire. ABI was measured by handheld doppler. ABI <0.9 was considered abnormal. The difference in mean distribution of ABI for risk factors was calculated by Student’s t-test and was considered statistically significant for P < 0.05. Odds ratios for various risk factors were calculated.

Results:
Based on ABI <0.9, PVD was diagnosed in 57 patients. There was a high prevalence of risk factors like age >55 years (67%), hypertension (66%), smoking (42%) and diabetes mellitus (35%). Mean ABI for hypertensive population is 0.85 (95% CI: 0.83-0.88, P=0.02). Mean ABI for smokers is 0.82 (95% CI:0.79-0.85, P=0.03). Mean ABI for diabetics is 0.80 (95% CI: 0.77-0.87, P=0.04). Multivariate risk analysis for PVD showed significant association with hypertension, smoking and diabetes but less significant for age, gender and family history.

Conclusion:
There is a very high prevalence of PVD in the Indian Population which can be attributed to modifiable risk factors as mentioned above. Defining the population at risk and using ABI as an early screening tool would help in prompt treatment and prevent further complications. A simple, inexpensive screening test like ABI is useful for diagnosing PVD in clinical practice. It helps prevent complications and consequent death by timely diagnosis and treatment.
Abstract 12716: Is Pre Existing Atrial Fibrillation a Risk Factor for Contrast Induced Nephropathy After Cardiac Catheterization?
Authors: Sedhai Yub Raj , Choksi Tatvam , Asija Ankush , Ahangar Waseem , Gevorgyan David , Golamari Reshma , Borikar Madhura , Missri Jose
Published: April 2024

Introduction:
Identifying patients at risk is an important step in preventing contrast-induced nephropathy (CIN). Several risk factors have been previously identified. We investigated to determine the association of pre-existing atrial fibrillation (AF) with the development of CIN after cardiac catheterization.

Methods:
A retrospective chart review of 513 patients who underwent cardiac catheterization from June to December 2014 was done. Patients with end-stage renal disease (n=38) & without pre-procedural serum creatinine (n=57) were excluded. Serum creatinine before the procedure & each day for three days after the procedure was recorded. CIN was defined as an increase in serum creatinine by ≥25% or ≥0.5mg/dl from the pre-procedural value within 72 hours of contrast exposure. Chronic kidney disease (CKD) was defined as eGFR <60ml/min calculated by modified diet in renal disease equation. Use of ICD 9 codes for atrial fibrillation & congestive heart failure (CHF) in admission medical records was defined as pre-existing AF & CHF.

Results:
A total of 418 patients (mean age 69.1 ± 13.8, 55% male and 45% female) were included in the study. 13% of patients had pre-existing AF, 27.9% had CHF & 19.6% had CKD. 16 patients of the total 418 developed CIN. The mean incidence of CIN in the population studied was 3.8%. Higher incidence of CIN was seen in AF, CHF & CKD groups when tested by univariate analysis & chi-squared test. The incidence of CIN was 13.8% in AF group Vs. 2.3% in non-AF group (p<0.001), 8.6% in CHF group Vs. 1.9% in non-CHF group (p<0.01) & 8.9% CKD group Vs. 2.4 % in non-CKD group (p<0.002). In multivariate logistic regression analysis, development of CIN was strongly associated with pre-existing AF. AF had odds ratio (OR) 4.11, 95% confidence interval (CI) 1.40-12.07, p=0.01. CHF had OR = 2.67, 95% CI, 0.89-7.98, p=0.08. CKD had OR=3.94, 95% CI, (1.56-9.98), p=0.04.

Conclusions:
Pre-existing atrial fibrillation may have an association with higher risk of CIN after cardiac catheterization in addition to conventional risk factors.
Abstract 12757: Prevalence and Outcome of Thrombotic and Embolic Complications in Adults After Fontan Operation
Authors: Egbe Alexander , Connolly Heidi , Niaz Talha , Driscoll David
Published: April 2024

Introduction:
There are limited studies of thrombotic and embolic complications (TEC) in the adult Fontan population.

Hypothesis/objectives:
To determine the prevalence, risk factors, and outcomes of TECs in this population.

Method:
Review of adults with a previous Fontan operation, followed at Mayo Clinic, 1994-2014. Systemic TEC was defined as intracardiac thrombus, ischemic stroke, or systemic arterial embolus. Non-systemic TEC was defined as Fontan conduit/right atrial thrombus or pulmonary embolus.

Results:
We identified 387 patients; mean age 28 ±7 years and follow-up 8±2 years. An atriopulmonary connection (APC) was done for 286/387 patients. Atrial arrhythmias were present in 278/387 (72%). There were 121 TECs (systemic n=36, non-systemic n=85) in 98/387 patients (25%). Risk factors for systemic TEC were atrial arrhythmia (hazard ratio [HR], 2.28;
P
=.001) and APC (HR, 1.98;
P
=.02); non-systemic TEC also had similar risk factors.

All 98 patients received warfarin but warfarin was discontinued in 10/98 because of bleeding; and 8 of these 10 had a second TEC after discontinuing warfarin. Thrombi resolution occurred in 16/82 (20%) that continued to receive warfarin 16 (20%) and had follow-up imaging; 8 with other comorbid conditions had Fontan conversion. In total, 24/98 patients had a second TEC, most of whom had inadequate anticoagulation.

Conclusions:
TEC was not uncommon; risk factors for TEC were APC and atrial arrhythmias. Most patients were treated successfully with warfarin alone. A second TEC occurred in most patients whose anticoagulation was discontinued because of bleeding events.

Legends
Kaplan-Meier Curves comparing freedom from TEC.

(A). Freedom from TECs in all patients and in patients with vs without atrial arrhythmia (AA) (
P
=.002).

(B). Freedom from TECs in all patients and in patients with vs without atriopulmonary connection (APC) (
P
=.001). “No APC” group comprise of patients with total cavopulmonary connections.
Abstract 12759: Utilization of Cardiac Rehabilitation Among Patients With Heart Failure
Authors: Park Linda G , Schopfer David W , Zhang Ning , Shen Hui , Vercammen Chris , Whooley Mary A
Published: April 2024

Introduction:
Cardiac rehabilitation (CR) is linked to reduced mortality and morbidity including improvements in cardiorespiratory fitness, psychosocial state, and quality of life in patients with heart failure (HF). However, little is known about CR utilization among patients with HF. We sought to determine: a) the proportion of patients with HF who participated in CR during a 5-year period; and b) patient characteristics associated with participation.

Methods:
A retrospective study was conducted using national data from the Centers for Medicare & Medicaid Services (CMS 5% random sample) and the Veterans Health Administration (VA) Healthcare System. We used primary discharge ICD-9 codes to identify all patients hospitalized for HF between 1/2007 and 12/2011. After excluding patients who died within 30 days of hospitalization, we identified participation in CR programs using CPT codes from Medicare and VA claims data. Multivariate logistic regression was used to identify patient characteristics independently associated with CR participation.

Results:
During the five-year study period, 66,710 Veteran patients and 243,208 of the 5% Medicare sample were hospitalized for HF. Of these, 1,554 Veterans (2.3%) and 6,280 Medicare beneficiaries (2.6%) attended one or more sessions of outpatient CR. Among Medicare beneficiaries, men were more likely than women to participate in CR (3.7% vs. 1.8%; p<0.001), but there was no gender difference in Veterans (2.3% vs. 2.8%; p=0.40). Characteristics associated with participation in CR among both VA and CMS patients included younger age, white race, and history of ischemic heart disease. Chronic conditions such as diabetes, chronic obstructive pulmonary disease, chronic kidney disease, and depression were associated with lower participation in CR.

Conclusions:
Very few HF patients participated in CR between 2007 and 2011, but participation was especially low among older, non-white women with a history of depression or other chronic medical conditions. Since Medicare has recently introduced coverage for CR in patients with systolic HF, we must increase efforts to improve CR participation, especially among these vulnerable groups.
Abstract 12776: Novel Left Ventricle Contractility Index as a Marker of Left Ventricular Function in Aortic Stenosis
Authors: Boey Elaine , Sim Hui Wen , Tan Benjamin , Lin Wei Qin , Zhong Liang , Tan Ru San , Kong William , Poh Kian Keong
Published: April 2024

Introduction:
The maximal rate of change of pressure-normalized wall stress dσ*/dt
max
is a novel, non-invasive, load-independent index of left ventricular (LV) global contractility. We aim to evaluate the relationship between dσ*/dt
max
and aortic stenosis (AS).

Methods:
417 patients with severe AS (aortic valve area [AVA] <1cm
2
) and no more than moderate concomitant other valvular pathology underwent echocardiography to characterise LV dimension, structure and dσ*/dt
max
. Univariate and multivariate analyses were performed.

Results:
Critical and non critical severe AS were defined as AVA≤0.8cm
2
and AVA≤1.0cm
2
respectively. Univariate analysis is presented in Table 1. dσ*/dt
max
was reduced in subjects with critical severe AS compared to non-critical severe AS (2.17± 0.79s-1 vs 2.46 ± 0.82s-1, p<0.001). Furthermore, dσ*/dt
max
was found to correlate with other indices of AS severity. Multivariate analysis showed that dσ*/dt
max
correlated with indexed AVA (B=0.20, p<0.001), LV ejection fraction (B=0.154, p<0.001), cardiac output (B=0.377, p<0.001) and LV mass index (B=-0.664, p<0.001). dσ*/dt
max
did not co-relate with age, gender, body mass index or body surface area.

Conclusions:
dσ*/dt
max
correlates with indices of AS severity and may be a reflection of underlying LV dysfunction in severe AS.
Abstract 12780: Impact of Atrial Fibrillation on Exercise Intolerance in Patients With Preserved Left Ventricular Ejection Fraction
Authors: Goto Toshihiko , Ishida Marina , Kikuchi Shohei , Wakami Kazuaki , Mori Kento , Fukuta Hidekatsu , Ohte Nobuyuki
Published: April 2024

Introduction:
When atrial fibrillation (AF) develops, there is loss of the atrial kick, with consequent decrease of cardiac output. Therefore, AF is recognized as an exacerbating factor for heart failure in patients with heart disease. However, the relationship between permanent AF and exercise intolerance in this population has been incompletely understood. Accordingly, we examined whether the presence of AF exacerbates exercise tolerance in patients with preserved left ventricular ejection fraction (LVEF).

Methods:
We studied 402 patients (age 68.0±9.6 years; male 67.5%) with 370 in sinus rhythm (SR) and with 32 in permanent AF. All patients had preserved LVEF (>50%) and were 40 years old or more. Patients underwent cardio-pulmonary exercise testing (CPX) including an analysis for oxygen uptake at peak exercise (peak VO
2
). Before CPX, comprehensive Doppler echocardiography was carried out. Early diastolic transmitral velocity (E) and mitral annular velocity during early diastole (e’) were measured.

Results:
No significant difference was found in age, body mass index, or the E/e’ ratio (9.0±3.2vs9.9±3.8, p=0.12) between the patients with SR and those with AF. Patients with SR had significantly higher LVEF (70.9±7.9vs66.2±8.7%, p=0.001) and higher proportion of female gender (34.9vs6.3%, p=0.001) than in those who with AF. Peak VO
2
did not differ between patients with AF and those with SR (19.2±5.2vs20.4±5.8ml/kg/min, p=0.28). In multiple logistic regression analysis, age (OR 3.7, 95%CI2.4-5.9, p<0.001) and female gender (OR 4.0, 95%CI 2.4-6.7, p<0.001) significantly contributed to exercise intolerance. However, the presence of AF (p=0.12) and higher LVEF (p=0.45) were not selected.

Conclusions:
Similar exercise tolerance was observed between patients with SR and those with permanent AF. These data suggest that permanent AF does not affect the exercise intolerance in patients with preserved LVEF.
Abstract 12783: Postoperative Cardioversions for New-onset Atrial Fibrillation in Cardiac Surgery
Authors: Kiviniemi Tuomas , Malmberg Markus , Biancari Fausto , Hartikainen Juha , Ihlberg Leo , Yannopoulos Fredrik , Riekkinen Teemu , von Hellens Otto , Lehto Joonas , Nissinen Maunu , Airaksinen Juhani K , Nieminen Tuomo
Published: April 2024

Introduction:
New-onset postoperative atrial fibrillation (AF) is a frequent complication after open-heart surgery and cardioversions (CV) are often performed to restore sinus rhythm in this setting. Thromboembolic risk related to early postoperative CV and the recurrence of AF in the long-term follow-up, however, remain largely unknown.

Hypothesis:
The FIN-bioAVR study sought to assess the rate of strokes and transient ischemic attacks (TIA) shortly after CV for AF in patients who underwent isolated aortic valve replacement with bioprosthesis.

Methods:
Between 2002 and 2014, 784 patients underwent isolated aortic valve replacement with a bioprosthesis in four Finnish University Hospitals.

Results:
During postoperative hospitalization when patients with prior chronic AF were excluded, 368/685 (53.7%) of patients had at least one new-onset paroxysm of AF (median time to diagnosis 3 [3] days), and early CV was performed in 122/368 (33.2%) of them. Baseline characteristics were comparable except that patients with CV had more often prior diagnosis of heart failure and less often chronic lung disease compared to those without CV. Hospital stay was significantly shorter, but at two-weeks follow-up, the rate of stroke/TIAs was 3.3% vs. 0.4% (p=0.05) in those with vs. without CV, respectively. Strikingly, early CV was associated with a trend of increased risk of two-week stroke/TIA rate compared to patients without CV (OR 7.66 (95%-CI 0.85-69.3, p=0.07)). In the median follow-up of 1682 [1514] days patients with early CV had more often recurrences of clinical AF (57% vs. 39%, p<0.01).

Conclusions:
In this large real-world population of patients undergoing aortic valve bioprosthesis operation, the rate of new-onset in-hospital AF was over 50%. Nearly third of them had a CV and these patients had over 7-fold risk for thromboembolisms related to CV.
Abstract 12797: Morphology and Type of Repair of the Atrioventricular Valve in Patients With Single Ventricle Undergoing Staged Palliation
Authors: Ono Masamichi , Burri Melchior , Cleuziou Julie , Pabst von Ohain Jelena , Beran Elisabeth , Hager Alfred , Schreiber Christian , Lange Rüdiger
Published: April 2024

Introduction:
Significant atrioventricular valve (AVV) regurgitation is a known predictor of adverse outcomes after the Fontan procedure. AVV morphology in single ventricle can be complex and the underlying mechanisms of AVV regurgitation are multifactorial.

Hypothesis:
We analyzed our experience with AVV repair in patients with single ventricle, focusing on the mechanisms of AVV regurgitation and repeat AVV surgery.

Methods:
Among 460 patients undergoing total cavopulmonary connection (TCPC), 81 (18%) had at least one AVV repair prior or at TCPC. Morphology and function of AVV, ventricular type, and prior palliative surgery were analyzed in all patients in order to identify the risk factors for AVV repair, redo AVV surgery, and AVV replacement.

Results:
AVV morphology was two separated AVV in 24 patients (30%), mitral in 5 (6%), tricuspid in 36 (44%), and common AVV in 16 (20%). The initial AVV repair was performed at a median age of 2.0 [0.9-4.0] years. AVV regurgitation was due to one or more of the following mechanism: dysplastic leaflet in 45 patients (56%), leaflet prolapse in 42 (52%), cleft in 19 (24%), and chordal anomaly in 11 (14%). These structural anomalies were observed in 69 patients (85%), and two or more anomalies were involved in 49 patients (61%). Pure annular dilation was observed in 12 patients (15%). A second surgery was necessary in 30 patients (37%) and a third in 5 (6%). The initial repair was needed earlier in patients with a leaflet prolapse (p=0.01). Repeat repair was frequently needed in patients with high degree of AVV regurgitation prior to initial surgery (p=0.02) and common AVV (p=0.002). AVV replacement was frequently needed in patients with chordal anomalies (p=0.002) and two or more anomalies (p=0.001).

Conclusions:
In the majority of the patients, structural anomalies of the AVV lead to regurgitation, and cause early need of initial repair, of repeat surgery, and of AVV replacement. High degree of AVV regurgitation prior to initial AVV repair was a risk factor for repeat surgery.
Abstract 12808: Public Access Defibrillation Has Great Impact on Outcomes After Pediatric Out-of-hospital Cardiac Arrest
Authors: Fukuda Tatsuma , Ohashi-Fukuda Naoko , Kobayashi Hiroaki , Gunshin Masataka , Kondo Yutaka , Yahagi Naoki
Published: April 2024

Introduction:
Use of automated external defibrillators (AEDs) has been recommended for pediatric out-of-hospital cardiac arrest (OHCA). Studies in adults suggest that public-access defibrillation (PAD) improves the outcomes after OHCA, but there have been no conclusive studies in children.

Hypothesis:
We assessed the hypothesis that PAD is associated with an increased chance of favorable outcomes after pediatric OHCA.

Methods:
This was a nationwide, population-based, propensity score-matched study of pediatric OHCA in Japan from January 1, 2011, to December 31, 2012, based on data from the All-Japan Utstein Registry. We included pediatric patients who experienced OHCA and received bystander CPR. The primary outcome was a favorable neurological state one month after OHCA defined as a Glasgow-Pittsburgh cerebral performance category (CPC) score of 1-2 (corresponding to a Pediatric CPC score of 1-3). The secondary outcomes included a neurologically favorable survival with a CPC score of 1 (corresponding to a Pediatric CPC score of 1), one-month survival, and prehospital return of spontaneous circulation (ROSC).

Results:
A total of 1,193 patients were included in the final cohort; 57 received PAD and 1,136 did not. Among 1,193 patients, 188 (15.8%) survived with a favorable neurological status one month after OHCA. The odds of neurologically favorable survival were significantly higher for patients receiving PAD after adjusting for potential confounders: propensity score matching, OR 3.17 (95%CI 1.40-7.17), and multivariable logistic regression modeling, OR 5.10 (95% CI 2.01-13.70). Similar findings were observed for the secondary outcomes. In subgroup analyses, there were no significant differences in neurologically favorable survival between PAD group and no PAD group in unwitnessed cohort (OR 7.76 [0.75-81.90]) and non-cardiac etiology cohort (OR6.65 [0.64-66.24]).

Conclusions:
In conclusion, PAD was associated with an increased chance of neurologically favorable survival after pediatric OHCA, except for unwitnessed cases and non-cardiac etiology cases.
Abstract 12829: Sodium Excretion and Risk of Cardiovascular Disease: A 20-year Follow-up Study
Authors: Zhou Long , Mai Jinzhuang , Li Ying , Gao Xiangmin , Wu Yong , Guo Min , Liu Xiaoqing , Zhao Liancheng
Published: April 2024

Introduction:
Effects of sodium intake and cardiovascular (CV) events from prospective cohort studies have been conflicting. The present study aims to estimate the effect of sodium excretion on cardiovascular disease in Chinese population.

Methods:
Data from the PRC-USA Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology were used in the analyses, including 880 men and women ages 35-59 years at baseline from 4 urban and rural population samples in Beijing and Guangzhou of China. Three timed 8-hour overnight urine samples were collected for each participant; the average of 3 times urinary sodium measurements were used. The association of urinary sodium categorized by tertiles with CV events was tested by Cox proportional hazards multivariable models.

Results:
At baseline, the mean (SD) estimated 8-hour overnight excretion for sodium was 63.48 (33.66) mmol. After a median follow-up of 20.25 years, the total CV outcome occurred in 64 (7.3%) participants, including 15 coronary heart disease (CHD) events (acute myocardial infarction, sudden cardiac death, or CHD death) and 52 stroke. From lowest (<44.28 mmol/8h) to highest (>=72.28 mmol/8h) tertile of sodium excretion, the cumulative incidence was 4.1%, 6.8%, and 10.9% for total CV events and 3.4%, 5.4%, and 8.9% for stroke. Compared with the lowest sodium excretion group, the Hazard Ratios (HRs) and 95% CI after adjustment for age, gender, site, type of work, smoke, alcohol drinking and serum total cholesterol for total CV outcome were 1.764 (0.853-3.647) and 2.745 (1.390-5.419) in middle (44.28-72.28 mmol/8h) and the highest sodium excretion groups, respectively. Furthermore, the HRs and 95% CI for stroke were 1.756 (0.789-3.912) and 2.737 (1.296-5.777) in middle and the highest sodium excretion groups, respectively. However, the association of sodium excretion with total CV outcome and stroke was not significant both in middle and the highest groups when we additionally adjusted for baseline systolic blood pressure.

Conclusions:
Higher urinary sodium excretion is associated with increased risk of CV events and stroke, but this relationship is not independent of baseline blood pressure levels.
Abstract 12899: Predictive Value of Markers of Collagen Turnover for Systolic and Diastolic Heart Failure: The MESA Study
Authors: Duprez Daniel , Gross Myron , Kizer Jorge R , Ix Joahim I , Hundley William G , Jacobs David R
Published: April 2024

Introduction:
Markers of collagen turnover have prognostic value in heart failure (HF), but the predictive value of these markers for incident heart failure in asymptomatic subjects is unknown.

Hypothesis:
Collagen turnover markers (Procollagen Type III N-Terminal Propeptide (PIIINP) and Collagen Type I Carboxy-Terminal Telopeptide (ICTP)) may be associated with new onset of HF (total, systolic and diastolic HF) in subjects free of overt cardiovascular disease (CVD) at baseline.

Methods:
We used a nested case-control design in a multi-ethnic sample of 3147 subject initially aged 45-84 years and free of CVD. We assayed baseline serum PIIINP and ICTP concentrations using radio-immunoassay. Incident HF (n=196) was based on medical records through a median 12.1 years of follow-up. Systolic HF (HFrEF) was defined if ejection fraction (EF) < 45 % and diastolic HF (HFpEF) if EF ≥ 45%. Poisson regressions were calculated using 2 models, adjusting for 1. Demographics (demog.) and estimated glomerular filtration (eGFrR) because ICTP is cleared by the kidney; 2. Model 1 + classical cardiovascular risk factors, and blood pressure and cholesterol lowering medication.

Results:
Mean (SD) ICTP was 3.38 ± 1.77 μg/L and Mean (SD) PIIINP was 5.48 ± 2.04 μg/L. Among 196 new HF cases, 95 were systolic HF (HFrEF) and 86 were diastolic HF (HFpEF); the 15 HF cases with no ejection fraction recorded were omitted from subtype analysis. In Poisson regression during 12.1 year follow-up (Table 1), Model 1 associations of ICTP and PIIINP with total HF and HFpEF were substantially attenuated in Model 2, although PIINP remained significantly associated with HFpEF.

Conclusion:
PIIINP as a marker of collagen turnover is predictive for incident HFpEF, in initially asymptomatic subjects free of overt cardiovascular disease, independently of classical cardiovascular risk factors.
Abstract 12929: Longitudinal Strain Distribution is a Powerful Predictor for Functional Recovery in Patients With Tachycardia-induced Cardiomyopathy
Authors: Kusunose Kenya , Yamada Hirotsugu , Saijo Yoshihito , Seno Hiromitsu , Hirata Yukina , Torii Yuta , Nishio Susumu , Ise Takayuki , Yamaguchi Koji , Yagi Shusuke , Soeki Takeshi , Wakatsuki Tetsuzo , Sata Masataka
Published: April 2024

Introduction:
Tachycardia-induced cardiomyopathy (TIC) is a potentially reversible cardiomyopathy by effective treatment of the tachyarrhythmia. However, cases without improvement of left ventricular (LV) systolic function were found occasionally. The diagnosis of TIC can be challenging, and the role of echocardiographic imaging in the prediction of LV functional recovery is limited.

Hypothesis:
We hypothesized that echocardiographic imaging might provide additional information to predict LV functional recovery in patients with tachyarrhythmia. The aim of this study was to assess the time course of LV functional recovery in presumptive TIC and the predictors of the recovery in such patients.

Methods:
We prospectively performed LV segmental longitudinal strains (LS) by 2-dimensional speckle tracking in 71 consecutive patients (65±16 years; 61% men) with tachyarrhythmia and reduced LV ejection fraction (EF) without any other known cardiovascular disease. Relative apical LS ratio (RALSR) was defined as a marker of strain distribution using following equation: average apical LS / (average basal LS + average mid LS).

Results:
Improvement in EF within 6 months after treatment of index arrhythmia was observed in 41 patients, and the EF did not improve in 30 patients. In univariate analysis, lower EF at baseline (hazard ratio: HR: 0.59 per 1SD, p=0.04) and higher RALSR (HR: 11.2 per 1SD, p <0.001) were associated with no recovery in the EF during follow-up. After adjustment for clinical variables, the significant predictor of LV systolic functional recovery was RALSR (HR: 22.1 per 1SD, p=0.001). A RALSR of 0.61 was sensitive (71%) and specific (90%) in differentiating LV systolic functional recovery (area under the curve: 0.88).

Conclusions:
The RALSR was associated with LV systolic functional recovery. This information might be useful for clinical evaluation and follow-up in patients with reduced EF.
Abstract 12960: Differential Pulse Arrival Time: A Novel Approach to Continuous Cuff-less Blood Pressure Monitoring
Authors: Pandit Jay A , Miller Kyle , Wu Jung-en , Connell Sean D , Shah Sanjiv
Published: April 2024

Introduction:
Blood pressure (BP) is a continuous and dynamic physiologic variable. The sphygmomanometer has forced clinicians to rely on singular snapshots of BP to make clinical decisions about BP control. Ambulatory cuff-based BP monitoring has demonstrated superiority over the conventional, single-point office-based cuff measurement and has unveiled the important concept of nocturnal BP dipping; however, it is plagued by poor compliance leading to limited use. Thus, there is an unmet need for an unobtrusive continuous ambulatory BP monitor. Current methods for continuous, non-invasive ambulatory BP monitoring include the use of vascular unloading and pulse transit time. However, both of these techniques have limitations. We therefore propose a novel method—differential pulse arrival time (DPAT)—to continuously estimate BP non-invasively. We hypothesized that continuous DPAT-derived BP correlates well with cuff-based measurement of BP at rest and during a cold-pressor maneuver.

Methods:
Normotensive subjects were fitted with a DPAT device and a Finapres Nova ambulatory BP monitor. Each subject underwent a standardized protocol consisting of 2 minutes at rest, 2 minutes cold pressor at 40
o
F, and 2 minutes at rest. The raw data from the DPAT device was then time-matched and compared with the Finapres BP trend.

Results:
Over 100 million DPAT data points were collected from 12 normotensive subjects (age range 20-50). DPAT correlated with Finapres blood pressures with a correlation coefficient of 0.8 and there was no evidence of bias on Bland-Altman plot. (Figure 1). The root mean square error for the predicted blood pressure was ±4.76 mmHg for systolic BP and ±4.03 mmHg for diastolic BP.

Conclusions:
Differential pulse arrival time obtained by an optical-sensor based system is a viable approach to monitoring continuous BP in normotensives. Future studies in elderly, hypertensive individuals are warranted.
Abstract 12980: Circulating Level of the Growth-Differentiation Factor-15 Is Increased in Dogs With Heart Failure and Normalized After Long-term Therapy With Elamipretide
Authors: Sabbah Hani N , Gupta Ramesh C , Singh-Gupta Vinita , Zhang Kefei , Xu Jiang
Published: April 2024

Introduction:
Growth-differentiation factor-15 (GDF15) is a stress-responsive cytokine produced in pathological states associated with tissue injury and inflammation. Increased level of GDF15 is an independent predictor of adverse prognosis (disease progression and mortality) in heart failure (HF). As a prognostic biomarker, GDF15 is independent of established biomarkers including BNP, troponins, or C-reactive protein (CRP). We previously showed that increased plasma levels of nt-pro BNP, tumor necrosis factor-α, interleukin-6 and CRP are normalized in dogs with HF following long-term therapy with Elamipretide (ELA,

Bendavia
TM

), a novel mitochondria targeting peptide. We also showed that therapy with ELA also prevents progressive LV dysfunction in dogs with HF.

Hypothesis:
This study tested the hypothesis that plasma level of GDF15 is increased in dogs with HF and is normalized after long-term therapy with ELA.

Methods:
Venous blood samples were obtained from 14 dogs at baseline (normal state) prior to induction of HF, after the induction of HF by intracoronary microembolizations but prior to any therapy and again at 3 months after initiating therapy with either subcutaneous ELA (0.5 mg/kg/day, n=7) or saline v/v (Control, n=7). Plasma levels of GDF15 were measured using a dog specific commercially available enzyme-linked immunosorbent assay (ELISA) kit (MyBiosource, San Diego, CA).

Results:
In untreated HF control dogs, plasma level of GDF15 was 326±32 pg/ml at baseline and increased to 744±124 pg/ml (p<0.05) when dogs were in HF and remained elevated at 3 months after initiating therapy with saline (728± 77 pg/ml). In dogs treated with ELA, plasma level of GDF15 was 314±29 pg/ml at baseline, increased to 875±71 pg/ml (p<0.05) when dogs were in HF and was restored to near normal levels at 3 months after initiating therapy with ELA (556±25 pg/ml, p<0.05 vs. pre-treatment).

Conclusions:
Circulating levels of GDF15 are increased in dogs with coronary microembolizations-induced HF. Long-term treatment with ELA reverses this increase, suggesting that inflammation-mediated injury may be reduced in dogs with HF treated with ELA. Restoring GDF15 by ELA therapy may be a useful indicator of beneficial response to therapy in patients with chronic HF.
Abstract 12996: Use of Premature Ventricular Extrastimuli During Supraventricular Tachycardia to Differentiate Atrioventricular Nodal Reentrant Tachycardia From Atrioventricular Reentrant Tachycardia
Authors: Ito Hiroyuki , Badhwar Nitish , Patel Akash R , Tanel Ronn E , Hoffmayer Kurt S , Pellegrini Cara N , Hsia Henry H , Vedantham Vasanth , Lee Randall J , Marcus Gregory M , Gerstenfeld Edward P , Scheinman Melvin M
Published: April 2024

Introduction:
Ventricular entrainment is useful to distinguish atrioventricular nodal reentrant tachycardia (AVNRT) from atrioventricular reentrant tachycardia (AVRT) by subtracting the ventriculoatrial (VA) interval during tachycardia from the interval between the last pacing stimulus and the last entrained atrial electrogram (SA). We tested the hypothesis whether induced right ventricular (RV) extrastimuli (V
2
) resetting tachycardia would be equivalent or superior to ventricular entrainment to distinguish AVNRT from AVRT.

Methods:
Patients with either AVNRT or AVRT who underwent electrophysiological study in three institutions were investigated. The entire tachycardia cycle length (TCL) was scanned with V
2
delivered from the RV apex. SA-VA differences were calculated with V
2
clearly resetting the tachycardia even when it was delivered prior to His refractory period. The prematurity of V
2
was assessed the V
2
coupling interval (CI) divided by the TCL.

Results:
A total of 189 patients (age 37.0 ± 22.3 years; 104 male) were included. There were 92 AVNRT (including 5 atypical forms) and 97 AVRT including 7 AVRT with decremental accessory pathway (AP). SA-VA difference was more than 70 ms in all AVNRT and was less than 70 ms in all AVRT with right and septal AP except those with decremental AP. There was significant negative correlation between SA-VA and CI/TCL ratio in both AVNRT and AVRT without decremental AP. A SA-VA difference <110 ms with CI/TCL less than 65% distinguished AVRT using left AP from AVNRT with sensitivity, specificity, positive and negative predictive values of 100%, 88%, 68%, and 100%, respectively. Ventricular entrainment resulted in tachycardia termination or AV dissociation in 31% compared with 16% using the V
2
technique (P = 0.0024).

Conclusions:
A SA-VA of 70 ms using the V
2
technique proved excellent for differentiation of AVNRT from AVRT using septal and right AP. There was overlap between AVNRT and AVRT with decremental AP or with left AP, but use of the V
2
technique with short CI (<65% TCL) differentiated AVNRT from AVRT using left AP. This technique less frequently resulted in tachycardia termination than ventricular entrainment.
Abstract 13018: Apoa1 Binding Protein Inhibits Retinal Angiogenesis by Up-regulating Notch Signaling
Authors: Mao Renfang , Miller Yury I , Fang Longhou
Published: April 2024

ApoA-1 binding protein (AIBP), a highly evolutionary conserved protein, plays a vital role in zebrafish angiogenesis, but its role of angiogenesis in higher vertebrate has not been studied. We thus propose that the role of AIBP in angiogenesis is also conserved from zebrafish to mice to humans. Since mouse models display tremendous power in the study of human cardiovascular disease as the murine and human vasculatures are highly similar. Therefore, we generated
Apoa1bp
-/-
mice, which are viable and fertile. We then compared retinal vasculature development in
Apoa1bp
-/-
mice and wild-type mice by whole mount immunostaining. Our data show that AIBP deficiency in mice results in significantly enhanced angiogenesis. Mechanically, We found the expressions of the Notch downstream targets
Hes1
,
Hey1
and
Hey2
were upregulated in
Apoa1bp
-/-
retinas compared to controls. And the protein level of Notch intracellular domain (NICD) was decreased in
Apoa1bp
-/-
retinas. These results suggest that the activity of the Notch signaling is decreased in retinas from
Apoa1bp
-/-
mice. Furthermore, we found AIBP affects on γ-secretase activity by enhance the colocaliztion of Notch1 and γ-secretase. Moreover, we studied whether increased HDL levels can rescue retinal angiogenesis in
Apoa1bp
-/-
mice. We crossed
ApoA1
transgenic mice with
Apoa1bp
-/-
mice. As expected, increased HDL levels rescued dysregulated angiogenesis in

Apoa1bp
-/-

mice, indicating that AIBP regulates angiogenesis through its effect on lipid rafts. Our study demonstrated that AIBP positively regulates the Notch signaling pathway by effect on lipid rafts, which in turn inhibits retinal angiogenesis. We are the first to connect AIBP, a cholesterol metabolism regulator, to Notch signaling.
Abstract 13019: Unique Changes in Electrocardiographic Metrics on Continuous Telemetry Prior to In-Hospital Cardiac Arrests Identified With Automated Algorithms
Authors: Kuo Alan , Do Duc H , Daniel Yazdi , Bai Yong , Ding Quan , Mortara David , Hu Xiao , Boyle Noel G
Published: April 2024

Introduction:
Despite advances, survival to discharge for in-hospital cardiac arrests (IHCA) remains less than 25%. Patients at risk of IHCA are often on continuous ECG monitoring, but no automated methods exist to leverage this information.

Hypothesis:
We hypothesize that ECG changes detectable with automated algorithms in the hours preceding IHCA may aid in predicting which patients are at risk of IHCA.

Methods:
We conducted a retrospective study on 79 IHCA and 1743 age-matched control patients. Telemetry data was processed with SuperECG (Mortara Instruments, Milwaukee, WI) for PR, QRS duration (QRSd), ST, QTc, RR, and QRS amplitude (AMP) metrics. Median, discontinuity, tachyarrhythmia and pacer dependence filters were applied. For cases, we selected the final (C1) and preceding (C2) 3-hour blocks before IHCA. For controls, we randomly selected two consecutive 3-hour blocks (T1, T2). C1 was compared to C2 and to a pooled control group (TP), consisting of T1 and T2, to identify changes unique to the final 3 hours. C2 was compared to TP, and T1 to T2 for internal control. Single and dual metric comparisons were performed. Maximal false positive rate of 5% was used to define thresholds for metric changes. We used chi-square testing and adjusted for multiple comparisons.

Results:
For C1 vs C2, we found higher percentages of significant QRSd prolongation (19.0% vs 3.8%, P=0.003) and AMP decrease (11.4% vs 1.3%, P=0.009). For C1 vs TP, we found higher percentages of QRSd prolongation (19.0% vs 4.6%, P<0.001), AMP decrease (11.4% vs 4.5%, P=0.004), and ST elevation (11.4% vs 3.0%, P<0.001). For dual metric comparisons, highest sensitivity was found with having both QRSd prolongation and ST elevation (C1 vs C2: 21.5% vs 3.8%, P<0.001 and C1 vs TP: 21.5% vs 4.7%, P<0.001). The sensitivity for meeting any single or dual metric comparison was 44.3% for C1 versus a specificity of 88.6% (P<0.001) for C2 and 86.5% (P<0.001) for TP. T1 vs T2 and C2 vs TP were statistically insignificant for all comparisons above.

Conclusions:
Significant ECG changes, identified by automated methods, are seen in the hours prior to IHCA. With further refinement and investigation, algorithms to detect ECG changes can be used in conjunction with traditional methods to help identify patients at risk of IHCA.
Abstract 13027: The Activation of Glucagon-Like Peptide-1 Improves the Mitochondrial Abnormalities in Skeletal Muscle and Exercise Intolerance in Heart Failure Mice
Authors: Katayama Takashi , Takada Shingo , Masaki Yoshihiro , Kinugawa Shintaro , Matsumoto Junichi , Nakajima Takayuki , Tsuda Masaya , Furihata Takaaki , Mizushima Wataru , Fukushima Arata , Yokota Takashi , Okita Koichi , Tsutsui Hiroyuki
Published: April 2024

Introduction:
In patients with heart failure (HF), exercise capacity is limited due to impaired energy metabolism and mitochondrial abnormalities in the skeletal muscle. Glucagon-like peptide-1 (GLP-1), one of the incretin hormones, has been indicated to improve exercise capacity in HF patients. We investigated the effects of the treatment of a dipeptidyl peptidase (DPP)-4 inhibitor on the limited exercise capacity and mitochondrial abnormalities in the skeletal muscle in HF mice after myocardial infarction (MI).

Methods and Results:
C57BL/6J male mice underwent surgery to ligate the left coronary artery or sham-operation. The mice were subsequently divided at random into groups with or without the treatment providing a DPP-4 inhibitor, MK-0626 (1 mg/kg body weight/day) in the diet. Four weeks after surgery, treadmill test and echocardiography were performed in 4 groups (n=14 each). The exercise capacity was limited in the MI mice, and it was improved in the MI+MK-0626 mice without affecting the infarct size, cardiac function, and skeletal muscle weight. The citrate synthase activity, mitochondrial oxidative phosphorylation capacity, fatty acid oxidation and their quantity were reduced in the skeletal muscle of the MI mice, and these decreases were normalized in the MI+MK-0626 group, in association with the improvement of mitochondrial biogenesis via phosphorylation of AMP-activated protein kinase (AMPK)-sirtuin1 (Sirt1)-peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α) signaling. Favorable effects of MK-0626 were significantly inhibited by treatment of GLP-1 antagonist, Excendin-(9-39) (150 pmol/kg body weight/min) with subcutaneous osmotic pumps in MI+MK-0626 mice. Similarly, exercise capacity and mitochondrial complex I activity were significantly improved by treatment of GLP-1 agonist, Excendin-4 (1 nmol/kg body weight/hour) with subcutaneous osmotic pumps in MI mice.

Conclusions:
The activation of GLP-1 receptor improves the reduced exercise capacity and mitochondrial abnormalities of skeletal muscle in HF mice after MI. The activation of GLP-1 receptor may be a novel therapeutic target against reduced exercise capacity and skeletal muscle dysfunction in HF.
Abstract 13032: Evidence of Dimensional Adaptability of in vivo Tissue-engineered Allogenic “Biotube” Vascular Grafts in a Growing Canine Model
Authors: Furukoshi Maya , Nakayama Yasuhide
Published: April 2024

Introduction:
In pediatric surgery, size mismatch inducing between artificial vascular grafts and growing recipients vessels remains a serious problem to be solved. Biotubes are autologous connective tissue tubes, formed by in body tissue architecture technology (IBTA), which is a novel and practical approach of regenerative medicine based on the tissue encapsulation phenomenon. This study aimed to evaluate the growth potential of Biotubes by examining their caliber and length adaptation to growing native arteries after implantation. Allogenic implantation of Biotubes pre-prepared from adult beagles was performed to juvenile beagles.

Methods and Results:
IBTA-based Biotubes (internal diameter 3 mm, length 1 cm) were prepared in adult beagles (age, 1 year; weight ca. 10 kg) by subcutaneous embedding of silicone-based molds for 2 months. The obtained allogenic collagenous Biotubes (n=8) were implanted into the common carotid artery (internal diameter, 2 mm) of juvenile beagles (n=8, age 11 weeks, weight ca. 3 kg). In all cases, there was no aneurysm or stenosis formation with perfect patency for all observation periods. Almost complete vascular remodeling occurred only at 1 month of implantation. Follow-up angiogram showed that diameter of Biotubes was gradually expanded with that of the growing host arteries almost in the same way. In 1-year after implantation, there was little gap between them by ca.1.5-times of diameter expansion in Biotube. Interestingly, macroscopic observation showed elongation of Biotubes to ca 1.3 times in maximum.

Conclusions:
Even in allogenic manner, vascular reconstruction of Biotube to layered vascular tissue successfully occurred. After vascular reconstruction, Biotubes could be extended and expanded according to the growing native arteries. The growth potential of Biotubes was indicated in this animal experimental model for the first time. Biotubes have high potential usefulness in pediatric surgery.