bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15697: Fingertip-Based Monitoring of Vascular Reactivity and Endothelial Function: A Three-Way Comparison of Testing Modalities
Authors: Naghavi Morteza , Lin Alex Wei Haw , Kleis Stanley , Yen Albert
Published: April 2024

Introduction:
In recent years fingertip-based measurement of vascular reactivity and endothelial function using a 5-min arm-cuff reactive hyperemia protocol has become a clinical tool for clinicians to evaluate patients in the exam room. Our group previously introduced Digital Thermal Monitoring (DTM) as a simple, easy and operator-independent test that measures vascular reactivity and endothelial function by monitoring fingertip temperature. Recently we developed fingertip photoplethysmography (PPG). In this study, we performed a simultaneous comparison of the three methods to evaluate their similarities and dissimilarities.

Hypothesis:
We hypothesized that PPG correlates strongly with PAT and could be used as a replace.

Methods:
Cuff-induced reactive hyperemia protocol (5 min. baseline, 5 min. ischemia, 5 min. post deflation) tests were performed with simultaneous recording of signals from PAT Pressure sensors (on index finger), DTM temperature sensors (3rd finger), and PPG photoelectric sensors (4th finger). A total of 39 tests were performed on 17 individual subjects. Signal data were analyzed, cross correlated, and graphed using Excel software and MATLAB functions.

Results:
As shown in Figure below, all three modalities showed similar patterns. Analyses of data during reactive hyperemia phase showed the strongest correlation between PPG and PAT (mean crosscorr = 0.79), compared to PAT and DTM (mean crosscorr = 0.64) and PPG and DTM (mean crosscorr = 0.49).

Conclusions:
DTM, PPG, and PAT signals are well correlated. The strong correlation between PPG and PAT suggests they can be used interchangeably.
Abstract 15700: L-type Calcium Channels Localization and Function are Affected by Microdomain Remodelling in Human Failing Cardiomyocytes
Authors: Sanchez-Alonso Jose L , Poulet Claire E , Schobesberger Sophie , Bhogal Navneet , Balijepalli Ravi C , Punjabi Prakash P , Gorelik Julia
Published: April 2024

Introduction:
L-type calcium channels (LTCCs) are essential in determining the electrical and mechanical properties of the cardiac muscle. LTCCs are located in specialized membrane microdomains in cardiac cells. Disruption of their microdomain localization in heart failure may contribute to the pathophysiology of cardiac disease.

Methods:
We studied isolated ventricular cardiomyocytes from patients with dilated cardiomyopathy with or without Left Ventricular Assistance Device (DCM or DCM+LVAD) versus those with normal ventricular function (nonfailing). Super-resolution scanning patch clamp provided topography images of the cell surface which enabled us to record LTCC current in distinct cellular compartments (T-tubules openings and areas between them, crests). Confocal microscopy was used to score T-tubular density and regularity in Di-8-ANEPPS stained cells. Expression of β2 subunit of LTCC was detected by immunofluorescence, Western blot and qPCR.

Results:
In failing cells T-tubular density is lower than in normal. The loss of cellular micro-architecture in failing cardiomyocytes leads to a redistribution of functional LTCCs from their usual location (T-tubules) to non-native crests of the sarcolemma. These relocated LTCCs in the crest of DCM cardiomyocytes have increased open probability and lower amplitude as compared with the channels located on the T-tubules. Interestingly, in cardiomyocytes isolated from patients with LVAD the open probability of LTCC is reduced dramatically and the amplitude recovers to the normal level, as does the T-tubular density. Immunostaining of DCM cardiomyocytes shows an increased amount of LTCC β2 subunit in the crest, and Western blot/qPCR shows more abundant expression of LTCC β2 subunit.

Conclusion:
In DCM cardiomyocytes a considerable amount of LTCCs improperly located on the crest microdomain display a pathologically high activity; this study suggests that the increased expression of LTCC β2-subunit could be responsible. Although LVAD cannot reverse the remodelling in DCM cardiomyocytes it helps to restore part of the microarchitecture of the cells and to normalize the function of the LTCCs.
Abstract 15788: Percutaneous and Surgical Carotid Artery Revascularization in Patients With Moderate and Severe (Stage 3 and 4) Chronic Kidney Disease: Insights of the Healthcare Cost and Utilization Project’s National Inpatient Sample
Authors: Lima Fabio V , Yen Tzyy Y , Gruberg Luis
Published: April 2024

Background:
Carotid artery stenting (CAS) has evolved into an alternative modality for the treatment of symptomatic and asymptomatic high-grade internal carotid artery stenosis, particularly in patients considered to be at a high surgical risk for carotid endarterectomy (CEA).

Hypothesis:
There is limited data on the outcomes of patients with moderate and severe chronic kidney disease (CKD) (GFR=15-59 mL/min/1.73m
2
) (Stage 3 and 4) undergoing CEA or CAS.

Methods:
The Healthcare Cost and Utilization Project’s National Inpatient Sample was screened for hospital admissions of patients undergoing CAS and CEA from 2003-2012. Clinical characteristics and outcomes were identified in patients with stage 3 and 4 CKD. The primary outcome of interest was in-hospital major adverse cardiac and cerebrovascular events (MACCE) defined as the composite of in-hospital death, acute myocardial infarction (AMI) and acute cerebrovascular accident (CVA).

Results:
Our study population consisted of 3,608 patients that underwent CEA and 746 patients that underwent CAS. Patients undergoing CAS had significantly higher rates of coronary artery disease and peripheral vascular disease with similar rates of hypertension, diabetes and hyperlipidemia. There was a higher rate of in-hospital MACCE in patients undergoing CAS compared with patients that underwent CEA, mainly driven by a higher rate of in-hospital strokes (Fig. 1). AMI and mortality rates were similar in both groups. In a multivariable analysis, CAS (OR 1.52, 95% CI 1.25-1.84) was independently predictive of MACCE.

Conclusions:
In patients with moderate and severe CKD, CAS was associated with similar rates of in-hospital mortality and AMI rates but higher rates of stroke when compared with CEA.
Abstract 11150: Hyperbaric Oxygenation Enhances Transplanted Cell Graft Survival and Functional Recovery in Critical Limb Ischemia
Authors: Takagi Gen , Miyamoto Masaaki , Kirinoki-Ichikawa Sonoko , Kubota Yoshiaki , Tara Shuhei , Hada Tomohito , Takagi Ikuyo , Shimizu Wataru
Published: April 2024

Introduction:
One of the major limitations in the application of stem-cell therapy to repair ischemic tissue is the low survival of transplanted cells, possibly due to poor oxygenation. Also the effect of hyperbaric oxygen therapy (HBOT) on bone marrow-derived mesenchymal stem cells (MSCs) is poorly understood.

Hypothesis:
We hypothesized that HBOT could be used as an adjuvant treatment to augment stem-cell therapy. Therefore, this study aimed to evaluate the effect of HBOT on the engraftment of bone marrow-derived MSCs transplanted in critical limb ischemia (CLI).

Methods:
Sixty-nine consecutive CLI patients refractory to peripheral revascularization therapy were enrolled. MSC transplantation was performed in all patients. HBOT (given 100% oxygen under 2.8 atmosphere absolute, for 60 min) was administered to 36 patients with and 33 patients without, by 2 weeks after those therapies. These patients were followed up by an outpatient clinic after limb survival. The primary endpoint was tissue oxygen tension of blood flow recovery, and secondary endpoint was adverse event rate (death and major limb amputation), analyzed by intention-to-treat.

Results:
Mean follow up was 11.4 ± 0.6 years. Limb survival rate was 84.1% and survival was 76.8%. The effect of HBOT was independent of background conditions, such as diabetes and hemodialysis (NS, respectively, Breslow-Day analysis). After 4 weeks, recovery of skin oxygen tension was significantly increased in MSC+HBO group compared to that in MSC group (22.7±16.3 to 34.5±21.4 vs 24.4±15.4 to 28.3±19.6, p = 0.045, odds ratio; 0.194). Surprisingly, in diabetic patients, MSC+HBOT group had significantly lower adverse event rate compared to MSC group (2 vs. 10 cases, p = 0.043, log-rank test, figure).

Conclusions:
HBOT appears to be a potential and clinically viable non-invasive adjuvant treatment for CLI stem-cell therapy.
Abstract 11198: Heritability of Vascular Structure and Function: A Parent-child Study
Authors: Ryder Justin R , Pankratz Nathan D , Dengel Donald R , Pankow James S , Jacobs David R , Sinaiko Alan R , Gooty Vasu , Steinberger Julia
Published: April 2024

Introduction:
Vascular structure and function can be measured non-invasively in both children and adults. Understanding the heritability of these measures may aid in risk stratification and atherosclerosis prevention efforts. Data on the heritable contribution from parent to offspring for vascular measures are limited.

Hypothesis:
We hypothesized that measures of vascular structure and function would be modestly heritable in this large parent-child study.

Methods:
High-resolution ultrasound scans of the brachial and carotid arteries were obtained in parents (n=558; mean age=39.2±2.1) and their offspring (n=369; mean age 12.4±4.6). In the brachial artery, flow-mediated dilation (FMD) and lumen diameter (bLD) were measured. In the carotid artery, intima-media thickness (cIMT), lumen diameter (cLD), incremental elastic modulus (cIEM), diameter distensibility (cDD), and cross-sectional distensibility were measured (cCSD). Carotid-radial pulse wave velocity (PWV) was also obtained. Heritability analysis (h
2
, expressed as %) was performed using SOLAR on the entire cohort and adjusted for age, gender, race, body-mass index, smoking, and systolic blood pressure. Data are presented as mean (SE).

Results:
Measures of bLD (h
2
= 25.2(8.6), p<0.001), cLD (h
2
= 55.4(8.8), p<0.001), cIMT (h
2
= 28.1(12.6), p=0.014), cDD (h
2
= 28.2(7.1), p<0.001), cCSD (h
2
= 27.1(6.9), p<0.001), and PWV (h
2
= 26.3(8.9), p<0.001) were significantly heritable. Only FMD (h
2
= 1.6(8.4), p=0.44), and cIEM (h
2
= 12.7(9.3), p=0.081) were not significantly heritable.

Conclusions:
These data suggest that the majority of non-invasive measures of vascular structure and function are modestly heritable from parent to child. Early interventions targeted at youth with elevated vascular risk and/or a high familial cardiovascular risk profile may be able to modify vascular structure and function to prevent further dysfunction as these children transition into adulthood.
Abstract 11270: Liver Disease as a Novel Risk Factor for Atrial Fibrillation
Authors: Huang William A , Dunipace Eric , Sorg Julie M , Vaseghi Marmar
Published: April 2024

Background:
End-stage liver disease can significantly affect circulating inflammatory peptides, creating a pro-arrhythmic substrate. However, liver disease as a risk factor for atrial fibrillation (AF) has not been previously studied and few studies have evaluated the incidence of AF in this population.

Objective:
The purpose of this study was to examine incidence of AF in patients with cirrhosis and assess liver disease severity as a risk factor for AF.

Methods:
A single center retrospective chart review of adult patients evaluated for orthotopic liver transplantation between 1/2006 and 12/2015 was performed. Model for End-stage Liver Disease (MELD) severity scores were calculated and presence of AF assessed from chart review and billing codes. Incidence of AF for MELD score severity was quantified and Cox proportional hazard models used to analyze effect of risk factors, including quartiles of MELD score, for AF occurrence.

Results:
Data from 1694 subjects (age 55±12 years, LVEF 61±7.4%) was analyzed. Mean MELD score was 16±8.5 and AF prevalence was 11.2%. Median follow up was 10.8 months (range 0.5-25). Hypertension was present in 12%, diabetes mellitus in 13%, sleep apnea in 0.7%, coronary artery disease (CAD) in 0.9%, valvular heart disease (VHD) 0.5%, and left ventricular hypertrophy (LVH) in 0.8%. After adjusting for age, gender, VHD, sleep apnea, diabetes, hypertension, LVEF, left atrial enlargement, and LVH, the highest quartile (MELD >30) had a HR of 12 (CI 5.3-29) with decreasing hazard ratios for the third (MELD = 21 to 30, HR of 6.8 (CI 3.8-12)) and second (MELD = 11 to 20, HR of 2.9 (CI 1.8-4.8)) compared to the lowest quartile (MELD = 1 to 10). Older age, sleep apnea, hemodynamic instability, VHD and lower LVEF also proved statistically significant.

Conclusion:
Patient with cirrhosis have a notable prevalence of AF. Severity of liver disease proved to be an independent risk factor for AF, even after accounting for other traditional risk factors.
Abstract 11276: Differentiating Cardiac Fibrosis From Hypertrophy in Chronic Kidney Disease Hemodialysis Patients Using Gadolinium-Free Imaging and Biomarkers of Extracellular Matrix Turnover
Authors: Stromp Tori A , Spear Tyler J , Kidney Rebecca M , Andres Kristin N , Kaine Joshua C , Charnigo Richard J , Leung Steve W , Sorrell Vincent L , Vandsburger Moriel H
Published: April 2024

Purpose:
Cardiac stress blood biomarkers are typically correlated to hypertrophy or diastolic dysfunction but not fibrosis in chronic kidney disease (CKD). Cardiac fibrosis can be measured without gadolinium as elevated normalized signal difference (ΔS/S
o
) between pairs of magnetization transfer (MT) weighted magnetic resonance (MRI) images. We used MT-MRI to compare blood biomarkers to fibrosis, hypertrophy and diastolic strain rate in CKD patients on hemodialysis (CKD5).

Hypothesis:
Biomarkers of cardiac stress correlate with left ventricular (LV) hypertrophy, not fibrosis, in CKD5 patients.

Methods:
MT-MRI generated maps of ΔS/S
o
in 23 CKD5 patients and 21 controls (Fig 1A, B). Fibrotic burden was defined as divergence in ΔS/S
o
compared to a standard distribution (Fig 1C). In a subset of 12-15 per group, serum troponin T (TnT), fibroblast growth factor 23 (FGF23), matrix metalloproteases (MMP) 2 and 9 and tissue inhibitor of MMP (TIMP) 1 and 2 were measured by ELISA and analyzed with Spearman correlations. Feature tracking measured strain.

Results:
CKD5 patients had higher ΔS/S
o
(146.2 ± 18.7%), divergence (10.0 ± 9.2%) and LV mass index (81.6 ± 28.9 g/m
2
) than controls (133.5 ± 11.5%, 5.4 ± 3.7%, 57.9 ± 15.5 g/m
2
, all
p
<0.05). Ejection fraction, diastolic strain rate and longitudinal strain were similar. While TnT, FGF23 and TIMP1/2 correlated with mass, only TIMP1 correlated with fibrotic burden (Table 1).

Conclusions:
Most stress biomarkers correlate with hypertrophy but not fibrosis in CKD5 patients. Activation of cardiac fibroblasts by TIMP1 and correlation of TIMP1 with degree of fibrosis suggest TIMP1 as an alternative target to attenuate cardiac fibrosis in CKD5 patients.
Abstract 11322: Multi-Institutional Analysis of Noninvasive Ventilation Practice After Infant Cardiac Surgery
Authors: Romans Ryan , Schwartz Steven , Costello John , Chanani Nikhil , Prodhan Parthak , Cooper David , Alten Jeffrey , Mistry Kshitij , Smith Andrew H , Gazit Avihu , Donohue Janet , Zhang Whenying , Gaies Michael
Published: April 2024

Background:
Hospitals performing infant cardiac surgery commonly use noninvasive ventilation (NIV) for postoperative respiratory support. The epidemiology of NIV use in this population remains unknown and it is unclear how practice varies across centers.

Methods:
We analyzed all infant surgical encounters (<1 year) in the Pediatric Cardiac Critical Care Consortium (PC
4
) registry from 10/2013--12/2015. NIV included high flow nasal cannula (HFNC) or positive airway pressure (PAP) support. We described patient, operative and postoperative characteristics of patients who did and did not received NIV. To examine casemix-adjusted duration of total respiratory support and the contribution of mechanical ventilation (MV) vs. NIV we created a model incorporating age, prematurity, extracardiac anomalies, surgical complexity and MV at preoperative admission. We calculated and compared adjusted mean duration of total support (MV + NIV), MV, and NIV across hospitals using observed-to-expected duration.

Results:
The cohort included 3708 encounters from 15 institutions: 2032 (55%) received NIV postoperatively, 40% were neonates, 36% were high complexity. Neonatal age group, extracardiac anomalies, single ventricle, procedure complexity, preoperative respiratory support, longer MV duration, and greater postoperative disease severity were all associated with NIV therapy vs. none (p<0.001 for all). Of those receiving NIV, 93% and 43% received HFNC and PAP, respectively. Across hospitals, NIV use ranged from 32%-65%, and adjusted mean duration ranged from 1-4 days (3 days observed mean). Differences in total adjusted respiratory support were largely driven by duration of MV (Figure 1).

Conclusions:
NIV therapy is common after infant cardiac surgery, though use varies across hospitals. The analysis suggests that initiatives to reduce differences across hospitals in postoperative respiratory support time should initially focus on MV practices, not NIV.
Abstract 11375: Hyperventilation Induced Coronary Vasospasm in a Man With Left Main Atresia With a Single Coronary Artery
Authors: Tariq M Umer , Zaheeruddin Samad , Celarier Amy , Odonoghue Susan , Gaglia Michael , Lipinski Michael
Published: April 2024

Introduction:
Coronary anomaly accounts for about a 3rd of sudden deaths in young individuals and coronary vasospasm in an anomalous coronary artery is very rare.

Case:
A 66 year old male with history of hypertension, diabetes & hyperlipidemia presented with syncope. He reported 2 months of episodic dyspnea, near-syncope, and epigastric pain. Stress cardiac magnetic resonance imaging demonstrated normal myocardial perfusion. While awaiting an electrophysiology study, he was observed to hyperventilate with associated epigastric pain, numbness and tingling followed by syncope with pulseless electrical activity arrest, receiving 2 minutes of cardiopulmonary resuscitation. Post-arrest electrocardiogram demonstrated posterior ST elevation MI so the patient was taken for coronary angiography which revealed congenital left main atresia with a single coronary artery taking the course of the right coronary artery giving rise to the left circumflex via the posterior lateral branch and then the left anterior descending artery (LAD) with mild to moderate disease (Fig 1). During the case, the patient had evidence of dynamic vasospasm in multiple segments that resolved with intracoronary nitroglycerin. All episodes of syncope/pre-syncope occurred after an episode of anxiety and hyperventilation, raising concern for hyperventilation-induced coronary vasospasm. Despite a trial with nifedipine, lorazepam and nitrates, he had another syncopal episode & was referred for coronary artery bypass surgery with left internal mammary artery to the LAD and saphenous vein graft to the obtuse marginal artery.

Discussion:
In this rare case, cardiac arrest was a result of coronary vasospasm which would result in global ischemia as the patient only had a single coronary artery, resulting in cardiovascular collapse with drop in cardiac output and pulseless arrest. This is the first case of vasospasm in a single coronary artery.
Abstract 11387: Examining Mortality Based on Changes in Peak Oxygen Consumption After Cardiac Rehabilitation
Authors: Kachur Sergey , De Schutter Alban , Lavie Carl , Jahangir Eiman , Dinshaw Homeyar , Milani Richard
Published: April 2024

Introduction:
Cardiac rehabilitation (CR) in stable coronary heart disease (CHD) has been shown to improve mortality commensurate with levels of improvement in cardiorespiratory fitness (CRF). We examine here if relative improvement is as important as absolute improvement on mortality.

Hypothesis:
We assessed the hypothesis that effects of absolute and relative changes in fitness, on mortality in a cardiac rehab population are different.

Methods:
890 subjects with stable CHD referred for CR were stratified according to baseline peak oxygen consumption (VO2) and post-CR improvement in VO2 (absolute group divided at 2.5 cc/kg/min, relative group divided at 20%) as measured during maximal cardiopulmonary exercise testing.

Results:
After adjusting for age, gender, left ventricular ejection fraction, baseline VO2, and body mass index, participants with higher absolute improvement had a twofold lower mortality (HR 0.56, p<0.001), whereas high relative improvement had no significant mortality effect. When post-rehab VO2 was used as a covariate, VO2 improvement was no longer associated with changes in mortality (HR 0.82, p = 0.37). High relative improvement without high absolute improvement was independently associated with increased mortality (HR 2.63, p<0.001, Figure 1) and lower baseline fitness (p < 0.001) than groups with high absolute improvement.

Conclusions:
In patients with CHD, absolute fitness after CR is the primary modulator of mortality, high absolute changes appear to be related to mortality benefits within the scope of increasing post-CR absolute CRF. This explains why high relative changes without associated absolute improvement reflects an especially low baseline CRF and high associated mortality. These results indicate that setting absolute targets for exercise capacity during CR can improve outcomes.
Abstract 11447: Interaction Between Alcohol Habits and Gene Polymorphism of Ghrelin on the Risk of Essential Hypertension in Japanese Population
Authors: Eto Masahiko , Okayama Masanobu , Takeshima Taro , Kumada Maki , Aonuma Takanori , Nakamura Yoshikazu , Kajii Eiji ,   The Jichi Community Genetics Team(JCOG)
Published: April 2024

Objectives:
To evaluate the interactions between SNP of ghrelin gene(
GHRL
) and alcohol habits on the risk of hypertension (HT:BP≥140/90) in Japanese.

Methods:
We analyzed 19036 Japanese subjects enrolled in the genome banking project at Jichi Medical University, including 8607 HT cases and 10429 non-HT controls.We divided the subjects into four groups according to gender and age (≤49 or ≥50).Alcohol habits were categorized to never, sometimes, and daily drinker for frequency of drinking. SNP rs696217(GG/GT/TT) of
GHRL
was genotyped by TaqMan method. Because the incidence of TT was low(<5%), GT and TT were combined together. The frequencies of genotypes, alcohol habits, and the combinations of both were compared between cases and controls by chi-squared test. The strength of the associations was estimated by logistic regression analysis. For the interaction, we assessed the joint ORs, which were calculated for each of six combined categories created by cross-classification. Non-risk genotypes as reference were different in M≤49(GG) and others(GT/TT).

Results:
(1)Genotype distributions significantly differed in F≤49. The frequencies of alcohol habits and combined categories significantly differed in all groups. (2) Compared to GG, the ORs (95%CI) of GT/TT were 1.25(1.0-1.55)* in M≤49. Compared to GT/TT, the ORs (95%CI) of GG were 1.57(1.20-2.06)* in F≤49, 1.01(0.90-1.13) in M≥50, and 1.04(0.93-1.16) in F≥50.(3) Compared to never drinkers, the ORs (95%CI) of daily drinkers were 1.77(1.32-2.37)* in M≤49, 1.26 (0.88-1.80) in F≤49, 1.64(1.44-1.87)* in M≥50, and 1.13(0.90-1.43) in F≥50. (4) Compared to never drinker with GG, the joint ORs (95%CI) of daily drinker with GG or GT/TT was 2.04(1.39-2.99)* and 2.34(1.55-3.54)* in M≤49. Compared to never drinker with GT/TT, the joint ORs (95%CI) of daily drinker with GT/TT or GG was 1.02(0.47-2.21) and 2.01(1.24-3.24)* in F≤49, 1.64(1.32-2.03)* and 1.70(1.40-2.08)* in M≥50, and 1.05(0.69-1.58) and 1.21(0.90-1.62) in F≥50 *(p<0.05).

Conclusions:
The interaction between
GHRL
rs696217 and alcohol habits had significant effects on HT risk in Japanese females≤49 years. The interactions between
GHRL
genotypes and alcohol habits may contribute to young-onset hypertension in Japanese females.
Abstract 11590: Liver Fibrosis Score Predicts Mortality in Heart Failure Patients With Preserved Ejection Fraction
Authors: Sato Yu , Yoshihisa Akiomi , Watanabe Shunsuke , Yokokawa Tetsuro , Miura Shunsuke , Sato Takamasa , Suzuki Satoshi , Oikawa Masayoshi , Kobayashi Atsushi , Yamaki Takayoshi , Kunii Hiroyuki , Saitoh Shu-ichi , Takeishi Yasuchika
Published: April 2024

Background:
Heart failure with preserved ejection fraction (HFpEF) has several pathophysiological aspects including stiffness of multiple organs. It has been recently reported that liver stiffness assessed by transient elastography predicts adverse prognosis in heart failure patients. Liver fibrosis is assessed by nonalcoholic fatty liver disease (NAFLD) fibrosis score (based on age, body mass index, aspartate aminotransferase [AST] to alanine aminotransferase [ALT] ratio, platelet counts and albumin) in patients with NAFLD. We aimed to investigate the impact of NAFLD fibrosis score on prognosis of HFpEF patients.

Methods and Results:
We analyzed consecutive 510 patients with HFpEF who admitted to our hospital. Out of these 510 HFpEF patients, patients with hepatitis and chronic liver disease were excluded, and 492 patients were finally analyzed. Liver fibrosis was estimated by NAFLD fibrosis score (= - 1.675 + 0.037 х age [years] + 0.094 х body mass index + 1.13 х diabetes mellitus [if presence, given 1] + 0.95 х AST [IU/L]/ ALT [IU/L] - 0.013 х platelet count [10-
9
/L] - 0.66 х albumin [mg/L]). These patients were divided into 4 groups based on the NAFLD fibrosis score: 1
st
(NAFLD fibrosis score < -1.13, n = 123), 2
nd
(-1.13 ≤ NAFLD fibrosis score < 0.20, n = 123), 3
rd
(0.20 ≤ NAFLD fibrosis score <1.56, n = 123) and 4
th
(1.56 ≤ NAFLD fibrosis score, n = 123) quartiles. In the follow-up period (mean 1107 days), 93 deaths (33 cardiac deaths and 60 non-cardiac deaths) occurred. In the Kaplan-Meier analysis, all-cause mortality progressively increased from 1
st
to 2
nd
, 3
rd
and 4
th
groups (8.1%, 12.2%, 23.6% and 31.7%, P <0.001). In the Cox proportional hazard analysis, after adjusting for potential confounding factors, NAFLD fibrosis score was an independent predictor of all-cause mortality in HFpEF patients (hazard ratio 1.98, 95% confidence interval 1.43-3.19, P < 0.001).

Conclusion:
NAFLD fibrosis score, a marker of liver fibrosis, can identify high risk patients with HFpEF.
Abstract 11603: Structural Insights Into C-terminus and N-terminus of a Designer cGMP Activating ANP-Based Antihypertensive Peptide: ZD100
Authors: Buglioni Alessia , Sangaralimgaham S Jeson , Huntley Brenda K , Harders Gerald E , McCormick Daniel J , Winaver Joseph , Chen Horng H , Burnett John C
Published: April 2024

Introduction:
As importantly underscored by the SPRINT Trial, innovative blood pressure (BP) lowering and multiorgan protective drugs are needed for treating hypertension (HTN). We engineered a Mayo Clinic designer atrial natriuretic peptide (ANP)-based drug, ZD100, which possesses a unique 12 amino acid (AA) carboxy-terminus (CT) extension while maintaining the N-terminus (NT) of ANP. ZD100 is more potent than ANP in reducing BP, inducing natriuresis and inhibiting aldosterone via pGC-A and its second messenger cGMP. To date, the in vivo actions of ZD100 in a model of essential HTN are undefined. Further, in attempt to enhance and/or minimize pGC-A activation, the importance of specific AAs in the CT and NT of ZD100 is unknown and is critical to define.

Hypothesis:
We hypothesize that ZD100 is a potent anti-HTN drug activating pGC-A/cGMP system and that specific AA variations in the CT and/or NT of ZD100 will modify the ability of activating pGC-A.

Methods:
Spontaneously hypertensive rats (SHRs) received intravenous (IV) ZD100 or vehicle and BP, plasma and urinary cGMP and the natriuretic effects were determined. We then engineered 15 strategic ZD100 variants (Vs) consisting of mutated peptides in the CT or NT or both. We stimulated HEK293 cells overexpressing pGC-A with ZD100 and the 15 Vs (10-8 M) and measured intracellular cGMP generation.

Results:
In SHRs, acute IV ZD100 reduced BP, increased plasma and urinary cGMP generation and induced natriuresis demonstrating efficacy in HTN. In vitro, we found two more potent pGC-A activators (+100% cGMP activation) only among the CT-only mutated ZD100 Vs. Importantly, key mutations of either the CT or NT resulted in 6 loss-of-function Vs identifying importance of peptide-receptor dependency.

Conclusions:
We demonstrate for the first time in a genetic model of HTN that ZD100 reduces BP, activates systemic and renal pGC-A/cGMP and induces natriuresis. Enhanced or reduced pGC-A activation with targeted AA mutations in the CT and NT of ZD100 provides key structure function insights into ZD100 which may lead to next generation ZD100 therapeutic peptides. These findings support ZD100 as a novel peptide therapeutic strategy for HTN and will help guide the selection of best-in-class ZD100 analogues.
Abstract 11638: Angiographic Efficacy of the Atriclip Left Atrial Appendage (LAA) Exclusion Device Placed by Minimally Invasive Thoracoscopic Approach
Authors: Patel Neel J , Aznaurov Sam , Ball Stephen K , Hoff Steven J , Adkins Keith , Carroll Amanda , Williams Jennifer R , Carr John J , Sandler Kim L , Ellis Christopher R
Published: April 2024

Introduction:
Closure of the LAA with an endocardial device is associated with a low risk for AF related embolic stroke. The Atriclip exclusion device (Atricure, Inc., West Chester, OH, USA) allows epicardial closure of the LAA, avoiding the need for oral anticoagulation (OAC) post procedure. We sought to assess long-term LAA closure efficacy of the Atriclip applied via totally thoracoscopic (TT) approach.

Hypothesis:
LAA closure efficacy will be high.

Methods:
We performed a prospective CT angiography (CTA) study of all TT placed Atriclips at Vanderbilt Medical Center implanted June 13, 2011 to October 6, 2015. All subjects provided informed consent under Vanderbilt IRB approved protocol. Intra-op TEE was performed in all cases to confirm procedural success. At a minimum of 90 days postimplant, 3-D volumetric two phase CTA was performed to assess the presence of contrast leak, exposed trabeculations, residual stump and clip position. All CTA interpretation and data was obtained by chest radiologists.

Results:
As of June 1, 2016, 63 patients completed CTA. The mean age was 64.8 ± 8.87 years and 77.8% were male. The majority of patients had persistent AF (82.5%). Mean CHADS2VASC score was 2.43 ± 1.44 and HASBLED was score 2.21 ± 1.23. Adequate LAA closure was defined as complete exclusion of the trabeculated LAA, which was confirmed in 59 subjects (93.6%). Cases without complete closure (n=4) include: 2 malpositioned clip not addressing a secondary LAA lobe, and 2 clips placed too distal leaving a stump with exposed trabeculae. Of the patients with complete closure, 30 (50.8%) had a smooth proximal stump. There were no major complications associated with TT placed Atriclips. Prospective follow-up over 143 observed patient-years reveals 1 stroke in a patient with documented complete LAA closure and no thrombus (hypertensive CVA).

Conclusions:
Angiographic LAA closure efficacy with a TT placed Atriclip is high (93.6%). The clinical significance of a remnant stump is unknown.
Abstract 11652: Sex-Specific Association of Retinal Microvascular Signs With Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis
Authors: Lin Gen-Min , Colangelo Laura Anne , Klein Ronald , Klein Barbara E.K. , Cotch Mary Frances , Wong Tien Y , Cheung Carol Y , Heckbert Susan R , Alonso Alvaro , Kwon Younghoon , Kronmal Richard A , Lloyd-Jones Donald M , Liu Kiang
Published: April 2024

Background:
Atrial fibrillation (AF) affects men more frequently than women in elderly individuals. Several risk factors have been identified; however the relationship of microvascular characteristics with AF is unclear. Assessment of the relationship of retinal microvascular signs with AF in men and women may provide insights into such a relationship.

Methods:
We prospectively examined the sex-specific association of retinal microvascular signs with incident AF events in 2,394 men and 2,618 women ages 47-86 years, who were free of prior AF, underwent fundus photography at the second exam (2002-2004) of the Multi-Ethnic Study of Atherosclerosis (MESA), and were followed through 2012. Retinal microvascular signs evaluated include retinal vascular caliber measurements from computer software (defined as the central retinal arteriolar equivalents (CRAE) and venular equivalents (CRVE)), and presence of retinopathy signs. AF events were identified using hospital discharge records, Medicare claims data, and electrocardiographic findings at visit.

Results:
Over an 8.8-year average follow-up period, 255 and 202 AF events were identified in men and women respectively. In Cox regression analyses, we adjusted for age, race, body mass index, smoking status, diabetes status, systolic blood pressure, lipid profile, HbA1c, C-reactive protein, anti-hypertensive therapy, lipid-lowering therapy, cardiovascular disease, and heart failure. In men, wider CRVE (wider venular diameter) was associated with lower risk of incident AF (hazard ratio [HR] and 95% confidence interval per 10-μm increase in CRVE: 0.92 [0.86-0.99]), whereas in women, wider CRVE was associated with higher risk of incident AF (HR: 1.09 [1.01-1.18], p-value for interaction of sex = 0.0023). There were no associations of CRAE or of any retinopathy with AF in men or women.

Conclusions:
We found associations of narrower retinal venular diameters in men and wider retinal venular diameters in women at baseline with the incidence of AF but with no evidence of relationships of retinal arteriolar diameters or the presence of any retinopathy at baseline to the incidence of AF in either men or women. The reasons for the interaction are not understood and its clinical relevance remains to be determined.
Abstract 11845: How Early Should We Initiate Targeted Temperature Management in Comatose Cardiac Arrest Survivors?
Authors: Lee ByungKook , Lee Dong Hun , Cho Yong Soo , Jeung Kyung Woon , Min Yong Il
Published: April 2024

Introduction:
The optimal time for initiation of targeted temperature management (TTM) in comatose cardiac arrest survivors has not been elucidated. We analyzed the association of time from return of spontaneous circulation (ROSC) to initiation of TTM and induction time with outcomes in cardiac arrest survivors.

Methods:
A retrospective analysis of data for adult comatose cardiac arrest survivors who were treated with TTM from 2008 to 2015 was conducted. Time from ROSC to initiation of TTM was defined as pre-induction time. Pre-induction time was divided into four groups as follows: ≤120, 121-240, 241-360, and ≥361 min. Additionally, it was divided by different binary cutoffs of 120, 180, 240, 300, 360, or 420 min to identify a threshold association. The primary endpoint was neurologic outcome at discharge.

Results:
The study included 478 patients; of these, 121 (25.3%) died, and 317 (66.3%) were discharged with poor neurologic outcomes. The median pre-induction time was 225 min (interquartile range [IQR], 155-300 min), and it differed according to good (202 min; IQR, 150-300 min) and poor (230 min; IQR, 160-310 min) neurologic outcomes (
p
=0.022). A multivariate logistic regression analysis revealed that delayed pre-induction (odds ratio [OR], 1.003; 95% confidence interval [CI], 1.001-1.005) and ≥361 min of pre-induction time (OR, 6.238; 95% CI, 1.928-19.628) compared to <120 min of pre-induction time were associated with poor neurologic outcome; however, 121-240 min (OR, 2.263; 95% CI, 0.969-5.284) and 241-360 min (OR, 2.111; 95% CI, 0.866-5.147) of pre-induction time were not associated with neurologic outcome. When the cohort was divided by cutoffs of 120 min (OR, 2.288; 95% CI, 1.044-5.012) and 360 min (OR, 2.679; 95% CI, 1.133-6.332), pre-induction time remained a significant predictor of poor neurologic outcome. Good neurologic outcome groups had a longer induction time. However, induction time was not an independent predictor of neurologic outcome.

Conclusions:
Delayed cooling was associated with increased poor neurologic outcomes at discharge among comatose cardiac arrest survivors treated with TTM. Patients with pre-induction time over 120 or 360 min had a higher probability of poor neurologic outcome.
Abstract 11854: Nationwide In-hospital Outcomes of Pregnancy in Women With Single Ventricle Congenital Heart Disease
Authors: Collins Ronnie T , Sandlin Adam , Chang Di , Goudie Anthony , Robbins James M
Published: April 2024

Introduction:
Most patients with single ventricle (SV) congenital heart disease (CHD) are expected to survive to adulthood. Women with SV are often counseled against pregnancy; however, data on pregnancies in these women are lacking. We sought to evaluate in-hospital outcomes of pregnancy in women with SV.

Methods:
We used nationally representative data from 1998 to 2012 Nationwide Inpatient Sample database to identify patients ≥ 18 years of age admitted to the hospital with International Classification of Diseases-9th Revision codes for an intrauterine pregnancy and a diagnosis of either hypoplastic left heart syndrome, tricuspid atresia or common ventricle. A matched comparison group without a diagnosis of CHD or pulmonary hypertension was identified from the database. National estimates of hospitalizations were calculated. Length of stay (LOS), total hospital charges, and cardiovascular complications were analyzed and compared between groups. Charge data were adjusted to 2012 dollars.

Results:
There were 310 admissions of pregnant women with SV (63% with deliveries) and 1547 admissions in the control group (91% with deliveries). There was no change in the annual number of SV pregnancies during the study period. Vaginal delivery was more common in SV (74% vs 72%, p<0.001). LOS (4.6 [0.98] days vs 2.5 [0.07], p<0.001) and charges ($38,627 [11,918] vs $13,880 [631], p<0.0001) were higher in SV. SV deliveries occurred more commonly in teaching hospitals (78% vs 51%, p<0.001). Complications occurred in nearly all SV admissions and were more common in SV compared to controls. (Table) There were no deaths in either group.

Conclusions:
Pregnancies in women with SV are associated with increased hospital resource utilization and cardiovascular complications, though in-hospital pregnancy related death is rare. Vaginal delivery is common in these patients. These data suggest that pregnancy and vaginal delivery are well tolerated in women with SV.
Abstract 11917: Muscarinic Stimulation Facilitates SR Ca
+2
Release by Increasing PKG Phosphorylation of RyR2 at Ser-2808 and Decreasing CaMKII Phosphorylation at Ser-2814
Authors: Ho Hsiang-Ting , Belevych Andriy E , Liu Bin , Bonilla Ingrid M , Radwanski Przemyslaw B , Valdivia Héctor H , Schober Karsten , Carnes Cynthia A , Györke Sándor
Published: April 2024

Autonomic regulation of SR Ca
+2
release is critical for modulating cardiac performance to match physiologic demand. During heart failure (HF), autonomic balanced shifts to a dominant sympathetic state to increase fractional SR Ca
+2
release. Although intended to be compensatory, this increase in sympathetic input causes increases in the frequency of proarrhythmic spontaneous SR Ca
+2
release events. Interestingly, parasympathetic augmentation was recently shown to alleviate HF phenotypes by shifting autonomic balance away from sympathetic dominance. While the effects of sympathetic stimulation and mechanism behind their action on cardiomyocyte Ca
+2
handling are relatively well established in health and disease, the modes of action and mechanisms of parasympathetic modulation of SR Ca
+2
release are poorly defined. To address this question, we investigated the effects of the cholinergic agonist, carbachol (CCH), on Ca
+2
handling (Fluo-4 FF AM) and protein phosphorylation levels in cardiomyocytes using a combination of pharmacological approaches and genetic mouse models. In settings of reduced SR Ca
+2
load, exposure to the parasympathetic agonist CCH increased fractional Ca
+2
release without affecting Ca
+2
spark frequency in cardiomyocytes. Immunoblot measurements showed that this “efficient” mode of excitation-contraction (EC) coupling involves reciprocal changes in the phosphorylation state of RyR2. Specifically, CCH treatment of cardiomyocytes increased Ser-2808 phosphorylation, mediated by muscarinic receptor subtype 2 and activation of PKG. Conversely, CCH treatment was associated with dephosphorylation at Ser-2814 through activation of muscarinic receptor subtype 3 and decreased ROS-dependent activation of CaMKII. We further demonstrate that parasympathetic stimulation improved Ca
+2
cycling efficiency in cardiomyocytes isolated from failing hearts by restoring altered RyR2 phosphorylation balance. These results suggest that parasympathetic stimulation initiates a novel mode of EC coupling in cardiomyocytes that enhances the efficiency of cardiac SR Ca
+2
store mobilization during systolic Ca
+2
release, while inhibiting pathologic diastolic Ca
+2
leak.
Abstract 11920: Electrocardiographic Predictors of Heart Failure With Reduced versus Preserved Ejection Fraction: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Mazur Matylda , O’Neal Wesley T , Bertoni Alain G , Bluemke David A , Al-Mallah Mouaz H , Lima Joao A , Kitzman Dalane W , Soliman Elsayed Z
Published: April 2024

Background:
A number of studies have shown usefulness of the electrocardiogram (ECG) in predicting heart failure (HF). However, whether these ECG predictors can distinguish between the risk of heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fraction is unknown.

Methods:
We analyzed data of 6,638 participants (53% female; mean age 62±10 years) from the Multi-Ethnic Study of Atherosclerosis who were free of cardiovascular disease at the time of enrollment. Digital ECGs were collected and centrally read at baseline (2000-2002) while HF was classified by an adjudication committee during a median follow-up of 11.2 years. A Cox competing risks analysis was used to compare the association of several ECG predictors with HFpEF and HFrEF.

Results:
A total of 226 HF events occurred during follow up, of which 116 events were HFrEF. Most of the ECG predictors of HF showed stronger associations with HFrEF than HFpEF. However, only a few showed a difference that reached statistical significance including prolonged QT, ST/T abnormalities and delayed QRS intrinsicoid deflection time (
Table
).

Conclusion:
Repolarization abnormalities and delayed ventricular activation may have the potential to distinguish between participants at future risk of HFrEF and HFpEF.
Abstract 11923: Perceived Discrimination and Cardiovascular Outcomes in Older African Americans: Insights From the Jackson Heart Study
Authors: Dunlay Shannon M , Lippmann Steven J , Greiner Melissa A , O’Brien Emily C , Chamberlain Alanna M , Mentz Robert J , Sims Mario
Published: April 2024

Introduction:
Perceived discrimination is known to play a role in the development of cardiovascular (CV) risk factors such as hypertension, but the association with CV outcomes is less clear. A recent report from a multi-ethnic cohort study found a modestly increased risk of CV disease in participants reporting discrimination. We explored this association in an African American (AA) cohort.

Hypothesis:
Greater perceived discrimination is associated with a higher risk of CV disease

Methods:
We examined CV outcomes among 5085 AAs in the Jackson Heart Study enrolled in 2000-2004 and followed through December 31, 2012. We stratified participants by quartiles of perceived everyday discrimination and estimated the associations with CV outcomes (all-cause mortality, incident coronary heart disease [CHD], incident stroke, and heart failure [HF] hospitalization) using Cox models.

Results:
Greater perceived discrimination was more common in participants who were younger, male, had higher education and income, a lower perceived standing in the community, worse perceived healthcare access, and fewer comorbidities. Over a median follow-up of 9.8 years (8.0 years for HF), 573 deaths, 193 incident CHD, 156 incident strokes, and 348 HF hospitalizations occurred. Prior to adjustment, greater perceived discrimination was associated with a lower risk of death, incident CHD, stroke, and HF hospitalization (Table). After adjustment for potential confounders, we found no association of perceived discrimination with incident CHD, stroke or HF hospitalization; however, a decrease in all-cause mortality risk with higher perceived discrimination persisted.

Conclusions:
We found no independent association of perceived discrimination with risk of incident CV disease or HF hospitalization and a paradoxical negative association with mortality in this AA population. The unexpected finding of a lower risk of death with greater perceived discrimination requires further study.
Abstract 11980: National Trends and In-hospital Outcomes During Delivery in Pregnant Women With Heart Disease in the US
Authors: Koutrolou-Sotiropoulou Paraskevi , Lima Fabio V , Yang Jie , Xu Jianjin , Stergiopoulos Kathleen
Published: April 2024

Background:
Investigation of trends and outcomes in heart disease (HD) and pregnancy has been limited.

Objective:
We chose to investigate the temporal trends and outcomes of pregnancy in women with HD in the US from 2003-2012.

Methods:
Healthcare Cost and Utilization Project’s National Inpatient Sample was screened for hospital admissions for delivery in pregnant women with HD from 2003-2012. Maternal clinical characteristics and outcomes were identified in women with and without HD, and in HD subtypes: congenital (CHD), valvular (VHD), cardiomyopathy (CDM), and pulmonary hypertension (PH). Primary outcomes of interest were prevalence, trends, and major adverse cardiac events (MACE), a composite of in-hospital death, acute myocardial infarction, heart failure, arrhythmia, cerebrovascular event, embolic events, or cardiac complications of anesthesia.

Results:
We studied 81,295 patients with HD and 39,894,032 without. CHD was the most frequent type (41.8%, 33,982 of 81,295), followed by VHD (30.9%, 25,138 of 81,295), CDM (20.8%, 16,926 of 81,295) and PH (6.5%, 5,250 of 81,295). MACE was highest among women with CDM and lowest in CHD (44.0%, 7,449 of 16,926 vs 6.2%, 2,102 of 33,982 p<0.0001). PH patients had the highest in-hospital death, followed by CDM (1.0%, 51 of 5,250 and 0.7%, 124 of 16,926 respectively). Pregnant women with HD significantly increased by 24.7%, related to increases in CDM, CHD, and PH. MACE significantly increased by 18.8%.

Conclusions:
Pregnancy in women with heart disease is increasing, particularly for high risk conditions such as CDM and PH. There is a significant and gradual increase in MACE for women with heart disease.