bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12941: MURC/Cavin-4 Deficiency Reduces Infarct Size and Preserves Cardiac Function in a Mouse Model of Ischemia-Reperfusion Injury
Authors: Nishi Masahiro , Ogata Takehiro , Nakanishi Naohiko , Kasahara Takeru , Maruyama Naoki , Higuchi Yusuke , Matoba Satoaki
Published: April 2024

Introduction:
Cardiac ischemia-reperfusion (I/R) injury is considered clinically important issue in cardioprotective strategy for ischemic heart disease. Muscle-restricted coiled-coil protein (MURC)/Cavin-4 is a member of the cavin family, which is a component of caveola. MURC/Cavin-4 is involved in myofibrillar organization by regulating Rho/ROCK signaling pathway and cardiac hypertrophy through ERK1/2 activation. MURC/Cavin-4 mutations are observed in patients with dilated cardiomyopathy. However, the role of MURC/Cavin-4 in cardiac I/R injury remains unknown.

Methods and Results:
Cardiac I/R was performed on MURC/Cavin-4-/- mice and WT mice. Mice were subjected to 1 hour ischemia by ligating left anterior descending artery, followed by 24 hours reperfusion. MURC/Cavin-4 mRNA expression was continuously increased after reperfusion in WT mouse hearts. Compared with WT mice, MURC/Cavin-4-/- mice exhibited significantly smaller infarct size (IS), which was assessed as proportion of the area at risk (AAR) (IS/AAR[%], MURC/Cavin-4-/- vs. WT: 52.7 ± 3.1 vs. 69.8 ± 12.3, p < 0.05). Echocardiography showed that MURC/Cavin-4 deficiency significantly preserved cardiac function (LVEF[%], MURC/Cavin-4-/- vs. WT: 54.2 ± 5.6 vs. 36.2 ± 2.0, p < 0.01; FS[%], MURC/Cavin-4-/- vs. WT: 27.0 ± 3.7 vs. 16.9 ± 1.1, p < 0.01, respectively). Hydrogen peroxide (H
2
O
2
), the most abundant form of reactive oxygen species (ROS) produced during I/R, causes inflammation, apoptosis and subsequent tissue damages. In neonatal rat cardiomyocytes, MURC/Cavin-4 siRNA reduced cell death induced by H
2
O
2
compared with control siRNA, as determined by TUNEL staining (TUNEL positive cells[%],MURC/Cavin-4 siRNA vs. control siRNA: 45.1 ± 7.2 vs. 65.7 ± 12.1, p < 0.05). Western blot analysis showed that p38 MAPK activation by H
2
O
2
was inhibited in cardiomyocytes transfected with MURC/Cavin-4 siRNA compared with control siRNA. Akt/PKB signaling was not influenced by MURC/Cavin-4 siRNA transfection.

Conclusions:
Our results indicate that MURC/Cavin-4 plays a crucial role in the development of cardiac I/R injury through ROS-induced apoptosis signaling pathway in cardiomyocytes. MURC/Cavin-4 might be a novel therapeutic target for cardiac I/R injury.
Abstract 12949: Elamipretide (
Bendavia
TM
) Restores 4-Hydroxy-2-Nonenal Protein Adducts and Aldehyde Dehydrogenase-2 Activity and mRNA Expression in Left Ventricular Myocardium of Dogs With Advanced Heart Failure
Authors: Gupta Ramesh C , Singh-Gupta Vinita , Zhang Kefei , Xu Jiang , Sabbah Hani N
Published: April 2024

Background:
4-hydroxy-2-nonenal (4HNE), a reactive aldehyde, is generated in the failing heart and contributes to cardiomyocyte injury and death. Aldehyde dehydrogenase-2 (ALDH2) plays a key role in detoxifying mitochondrial (MITO) reactive aldehydes. We showed that chronic therapy with elamipretide (ELA), a novel MITO targeting peptide, improves LV systolic function, normalizes MITO function and reduces the burden of reactive oxygen species (ROS) in LV of dogs with microembolization-induced heart failure (HF).

Hypothesis:
This study tested the hypothesis that chronic therapy with ELA normalizes protein levels of 4-HNE-adducts and ALDH2 activity and expression in LV myocardium of HF dogs (LV ejection fraction ~30%).

Methods:
LV tissue from 14 HF dogs randomized to 3 months therapy with subcutaneous injections of ELA (0.5 mg/kg once daily, n=7) or subcutaneous injections of saline (control, CTR, n=7) and tissue from 6 normal (NL) dogs was used in the study. Level of 4-HNE-protein adducts was quantified using an Elisa kit. ALDH2 activity was assayed spectrophotometrically in LV MITO fractions by monitoring NADH formation from NAD to NADH at 340 nm. Protein levels of ALDH2 and porin (an internal loading control) were determined by Western blotting and band intensity quantified in densitometric units (du). mRNA expression of ALDH2 and GAPDH was measured in using real-time PCR.

Results:
Data are shown in the table. Levels of 4HNE-protein adducts were significantly increased and ALDH2 activity, mRNA expression and protein levels significantly decreased in CTR compared to NL dogs. ELA normalized 4-HNE levels, ALDH2 activity and expression. There were no differences in the level of porin or GAPDH among the 3 study groups.

Conclusions:
Chronic therapy with ELA normalizes ALDH2 and 4-HNE levels in LV myocardium of HF dogs. By limiting myocardial ROS burden, ELA contributes to cardiac end-organ protection and hence, to overall improvement in global LV function.
Abstract 12973: PR-Interval Components and Atrial Fibrillation Risk: The Atherosclerosis Risk In Communities Study
Authors: O’Neal Wesley T , Smith Justin W , Shoemaker M. B , Chen Lin Y , Alonso Alvaro , Whalen S. P , Soliman Elsayed Z
Published: April 2024

Introduction:
Reports on the association between the PR-interval and atrial fibrillation (AF) are conflicting. We hypothesized that inconsistencies stem from that fact that the PR-interval is not a single electrocardiographic (ECG) phenotype and it is more likely to represent a composite of several distinct components.

Methods:
We examined the association of the PR-interval and its components (P-wave onset to P-wave peak duration, P-wave peak to P-wave end duration, and PR-segment) with AF in 14,924 participants (mean age=54±5.8 years; 26% black; 55% female) from the Atherosclerosis Risk in Communities study. The PR-interval and its components were automatically measured at baseline (1987-1989) from standard 12-lead ECGs. PR-interval >200 ms was considered prolonged and values >95th percentile defined abnormal PR-interval components. AF was ascertained during follow-up through December 31, 2010.

Results:
Over a median follow-up of 21.2 years, 1,985 (13%) participants developed AF. Prolonged PR-interval was associated with an increased risk of AF (HR=1.19, 95% CI=1.02, 1.40). However, PR-interval components showed varying levels of associations with AF (P-wave onset to P-wave peak duration: HR=1.57, 95%CI=1.31, 1.88; P-wave peak to P-wave end duration: HR=1.20, 95%CI=0.99, 1.46; and PR-segment: HR=1.05, 95%CI=0.85, 1.29). Additionally, the components of the PR-interval had weak to moderate correlation with each other (correlation r ranged from -0.44 to 0.06).

Conclusions:
Our findings suggest the PR-interval represents a composite of distinct components that are not uniformly associated with AF. Without considering the contribution of each component, inconsistent associations between the PR-interval and AF are inevitable.
Abstract 12975: Electrocardiographic Left Ventricular Hypertrophy Predicts Atrial Fibrillation Independent of Left Ventricular Anatomy
Authors: Patel Nikhil , O’Neal Wesley T , Whalen S. P , Soliman Elsayed Z
Published: April 2024

Introduction:
It has been established that LVH detected by electrocardiography (ECG-LVH) and LVH detected by echocardiography (echo-LVH) carry different prognostic profiles in the prediction of cardiovascular disease events. It remains unclear whether ECG-LVH and echo-LVH are independently predictive of atrial fibrillation (AF).

Methods:
This analysis included 4,904 white participants (40% male; 85% white) aged 65 years or older from the Cardiovascular Health Study who were free of baseline AF and major intraventricular conduction defects. ECG-LVH was defined by Minnesota ECG Classification criteria from baseline ECG data. Echo-LVH was defined by sex-specific left ventricular mass values >95th percentile for the study population. Incident AF events were identified during the annual study ECGs and from hospitalization discharge data. Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) for the association of ECG-LVH and echo-LVH with adjudicated incident AF events, separately.

Results:
ECG-LVH was detected in 224 (4.6%) participants and echo-LVH was present in 231 (4.7%) participants. Over a median follow-up of 11.9 years, a total of 1,430 AF events were detected. In a multivariable Cox model adjusted for age, sex, race, education, income, body mass index, high-density lipoprotein cholesterol, total cholesterol, smoking, systolic blood pressure, diabetes, aspirin, antihypertensive medications, valve disease, coronary heart disease, and heart failure, ECG-LVH (HR=1.44; 95%CI=1.14, 1.83) and echo-LVH (HR=1.42; 95%CI=1.11, 1.82) were independently associated with AF. When ECG-LVH (HR=1.42, 95%CI=1.12, 1.80) and echo-LVH (HR=1.40, 1.09, 1.79) were included in the same model, both were predictive of incident AF.

Conclusions:
The association of ECG-LVH with AF is not dependent on abnormalities of left ventricular anatomy. These data suggest that abnormalities in cardiac electrophysiology provide a distinct profile in the prediction of AF.
Abstract 12995: Prevalence and Incidence of Atrial Fibrillation in a Population Implanted With Cardiac Resynchronization Therapy Devices Implanted for at Least 30 Days: Evidence From a Prospective Clinical Trial
Authors: Hayes David L , Monteiro Joao V , Klepfer Ruth , Grenz Nathan A , Tsintzos Stelios I , Eggington Simon , Shah Bimal R
Published: April 2024

Introduction:
Atrial Fibrillation (AF) is an important contributor to insufficient left ventricular pacing and mortality in patients undergoing cardiac resynchronization therapy (CRT). The incidence and prevalence of AF post-CRT implant, in patients with and without previous history of AF, has not previously been described.

Hypothesis:
AF prevalence in CRT patients, despite history of AF, is higher than previously understood.

Methods:
Subjects implanted with a CRT-Defibrillator (CRT-D) enrolled in the PainFree SST study and with device data collection were analyzed. Subjects who exited within 30 days of implant, had < 27 days of available daily AT/AF burden data, or had ≥ 10% of daily AT/AF data missing were excluded. We defined incidence and prevalence of clinically meaningful device documented AF using previously published criteria (≥1 day with AF > 6 hours). History of AF at enrollment was documented based on clinical history.

Results:
The analysis included 944 patients (68±11 years; 78% male, EF 28±9%, QRS 152±29 ms; 59% NYHA III/IV). The duration from implant to study exit or death was 2.0 ± 0.8 years (IQR 1.5-2.5). History of AT/AF was documented in 37% of patients at baseline. Overall, any AT/AF was found in 85.2 % of subjects during follow-up. Clinically meaningful AT/AF was found in 30.3% of subjects. Of the 345 subjects with history of AF at baseline, 51.9% had clinically meaningful AT/AF during follow-up vs.17.9% for subjects without known AF (p<0.0001). 24.8% of subjects experienced at least one day of ≥ 23h of AT/AF. 6.9% of subjects had ≥ 23h of AT/AF for > 95% of days with data.

Conclusions:
AF occurs in a substantial proportion of CRT-D patients and clinically documented history of AF prior to CRT-D implant corresponds poorly with device documented AT/AF during follow-up. Device documented AF should be evaluated in CRT-D patients with and without previous history of AF to individualize strategies to maximize left ventricular pacing and minimize disruption due to AF.
Abstract 13000: Physical Activity is Associated With Reduced Left Ventricular Mass Index in Blacks: Insights From the Genetic Epidemiology Network of Arteriopathy (GENOA) Study
Authors: Kamimura Daisuke , Suzuki Takeki , Wang Wanmei , Mosley Thomas H , Butler Kenneth R , Hall Michael E
Published: April 2024

Background:
Physical activity (PA) has been associated with decreased left ventricular hypertrophy (LVH) in some clinical studies, however factors which influence this relationship have yet to be clarified. Blacks are disproportionately affected by cardiac diseases including LVH, partly due to higher rates of hypertension and obesity. Because other factors may also play a role, we investigated clinical factors that may affect the relationship between PA and LVH in blacks.

Methods and Results:
We evaluated 1314 black participants with preserved LV ejection fraction (EF>50%) from the Genetic Epidemiology Network of Arteriopathy (GENOA) Study (mean age 62.4 years, 73% women). LV mass index (LVMI) was calculated from echocardiography using the

Devereux

formula and indexed by height
2.7
. Total hours of PA per day (TPA hours) were assessed by self-report. The relationship between TPA hours and LVMI was evaluated by generalized estimating equation (GEE) with identity link, and adjusted for possible confounders. The effect of TPA hours on LVMI by age group, sex, body mass index (BMI), history of hypertension, diabetes or coronary heart disease, estimated glomerular filtration rate and current smoking status were plotted. After adjustment for these factors, longer TPA hours were independently associated with lower LVMI (p<0.05). There were significant interactions between TPA hours and obesity (BMI≥30), and history of hypertension on LVMI (p for interaction <0.05, for both, Figure). Longer TPA hours were associated with lower LVMI more in obese or hypertensive participants compared to non-obese or non-hypertensive participants.

Conclusions:
More PA was associated with lower LVMI in blacks. The protective effect of PA against LVH was present in obese and hypertensive black participants illustrating the importance of recommending increasing PA to prevent LVH and potentially reduce the risk of heart failure.
Abstract 13013: Associations Between Unplanned Cardiac Reinterventions and Early Outcomes After Pediatric Cardiac Surgery: Findings From the Society of Thoracic Surgeons Congenital Heart Surgery Database
Authors: Costello John M , Monge Michael C , Hill Kevin D , Kim Sung Hee , Pasquali Sara K , Yerokun Babatunde , Jacobs Jeffrey P , Backer Carl L , Mazwi Mjaye L , Jacobs Marshall L
Published: April 2024

Introduction:
In children undergoing cardiac surgery, we sought to determine the incidence of unplanned cardiac reinterventions (surgery or therapeutic catheterization) during the same hospitalization as the index operation, identify risk factors for reinterventions, and explore associations between unplanned reinterventions and adverse outcomes.

Hypothesis:
We hypothesized that younger patients undergoing more complex operations would be at greater risk for unplanned cardiac reinterventions, and that operative mortality and postoperative length of stay (LOS) would be greater in patients who undergo reintervention when compared to those who do not.

Methods:
Patients ≤18 years of age in the STS Congenital Heart Surgery Database from January 2010-June 2015 were included. Multivariable logistic regression was used to evaluate risk factors for unplanned reintervention, and the impact of reintervention on outcomes including operative mortality and post-operative LOS. Covariates were included to adjust for important patient characteristics (e.g., weight, age, and comorbidities), case complexity, and center effects.

Results:
Included were 84,404 patients from 117 centers, of whom 21% were neonates and 36% infants. An unplanned cardiac reintervention was performed in 5.4% of patients, including 11.8% of neonates, 5.2% of infants, and 2.8% of children. Independent risk factors for an unplanned reintervention included presence of non-cardiac anomalies and genetic syndromes, non-Caucasian race, younger age, lower weight among neonates and infants, prior cardiothoracic operations, preoperative mechanical ventilation, preoperative risk factors, and higher STAT Mortality Category (adjusted p<0.001 for all). The performance of an unplanned reintervention was an independent risk factor for operative mortality (adjusted OR, 5.34, 95% CI, 4.83-5.91, p<0.001) and longer post-operative LOS (adjusted RR=2.31, 95% CI, 2.20-2.42, p<0.001).

Conclusions:
Unplanned cardiac reinterventions are not rare, particularly in neonates, and are independently associated with mortality and increased post-operative LOS. Patients at greater risk may be readily identified preoperatively, presenting opportunities for quality improvement.
Abstract 13063: Dapagliflozin Provides Multiple Ultrasonic-Evaluated Antiatherosclerotic Effects Independent of Diabetic Improvement for Type-2 Diabetics With Coronary Artery Disease Receiving Statin or Sartan
Authors: Murakami Tatsuaki , Ohsato Kazuo
Published: April 2024

Introduction:
Diabetes mellitus is thought to be highly involved in complex atherothrombogenic processes, but the antiatherosclerotic therapies in patients with type-2 diabetes mellitus have not been established.

Hypothesis:
We assessed hypothesis that antidiabetic therapy with dapagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, pleiotropically inhibits atherosclerotic progression in patients with type-2 diabetes mellitus treated by statin or sartan, one of the best possible antiatherosclerotic therapies.

Methods:
Type-2 diabetic patients with stable coronary artery disease taking statin or sartan were randomized to group-D where they received antidiabetic therapy with dapagliflozin for 6 months, or to group-C where they received enhanced therapies with conventional antidiabetic agents without an SGLT2 inhibitor. We quantified flow-mediated endothelium-dependent dilatation of brachial artery after transient forearm occlusion (FMD), and also quantified intima-media thickness of brachial artery (IMT) using high-resolution ultrasonography. Changes in FMD, IMT, and other metabolic variables were compared between the 2 groups.

Results:
Glycemic variables represented by HbA1c significantly improved in both groups. All patients in group-D (n=20) manifested good compliance and significant improvements in multiple metabolic variables, while those in group-C (n=10) showed no improvement. In group-D FMD (%) significantly increased (from 3.4±2.5 to 6.3±2.3, p<0.01) and IMT (mm) significantly decreased (from 0.33±0.06 to 0.30±0.05, p=0.04), while both FMD (from 3.6±2.3 to 3.8±2.4, p=0.72) and IMT (from 0.34±0.12 to 0.35±0.14, p=0.84) remained unchanged in group-C. Changes of FMD or IMT in group-D did not correlate to those of HbA1c (FMD: r=0.14, p=0.69, IMT: r=0.10, p=0.72).

Conclusions:
These results indicate inhibition of sodium glucose co-transporter-2 with dapagliflozin improves endothelial function, and reduces arterial wall thickening independent of glucose lowering, which may have novel potential benefit of dapagliflozin for management of progressive atherosclerosis in type-2 diabetics with coronary artery disease treated by statin or sartan one of the best possible antiatherosclerotic therapies.
Abstract 13135: The Clinical Significance of Intraoperative Iloprost Inhalation on Outcome of High Risk Cardiac Surgical Patients: A Multicenter Randomized Controlled Trial
Authors: Winterhalter Michael , Rex Steffen , Stoppe Christian , Kienbaum Peter , Müller Hans-Helge , Kaufmann Ines , Dongas Aristidis , Kuppe Hermann , Zwissler Bernhard
Published: April 2024

Background:
Perioperative right ventricular (RV) failure due to pressure overload resulting from pulmonary hypertension (PH) worsens postoperative outcomes in cardiac surgery. Inhaled iloprost is a potent pulmonary vasodilator improving biventricular performance, ameliorating myocardial and pulmonary ischemia-reperfusion injury and attenuating inflammation. We hypothesized that the prophylactic inhalation of iloprost improves postoperative outcome in patients undergoing elective open heart surgery being at an increased risk for perioperative RV failure.

Methods and Results:
In this phase 3, multicenter, randomized, double-blind, placebo-controlled trial, we randomly assigned 253 cardiac surgical patients at high risk for perioperative RV failure to the prophylactic inhalation of 20μg iloprost or placebo before and during weaning from extracorporeal circulation (ECC). The primary endpoint was the duration of postoperative ventilation. Secondary endpoints included perioperative hemodynamics, intensive care unit and hospital length of stay, and 90-days mortality. Safety was assessed by the incidences of adverse events. Iloprost had no significant effect on the time until extubation (iloprost: median: 720min [first quartile, third quartile][540min; 1218min]; placebo: 780min [468min; 1170min]; p=0.37). While the nebulization of iloprost decreased RV afterload and improved cardiac index, major secondary endpoints were not significantly affected. Treatment with iloprost was safe with the incidences of adverse events not differing between groups.

Conclusions:
The prophylactic inhalation of iloprost does not result in any meaningful improvement of perioperative morbidity and outcome in high-risk cardiac surgical patients.

Clinical Trial Registration:
URL:
http://www.clinicaltrialsregister.eu
. Unique identifier: EudraCT-number: 2008-002090-12; URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00927654
Abstract 13186: Rare and Low Frequency Variants Associated With Hypertension and Systolic Blood Pressure in Taiwan Chinese Families
Authors: de las Fuentes Lisa , Schwander Karen L , Sung Yun Ju , Hsiung Chao Agnes , Sheu Wayne , Hixson James E , Taylor Kent D , Rotter Jerome I , Rao D. C , Chen Ida ,   and the THRV Study
Published: April 2024

Introduction:
Hypertension (HTN) and related disorders constitute a major public-health burden. While genome-wide association studies have identified common variants for HTN, <2.5% of blood pressure (BP) variance has been explained.

Hypothesis:
Exome sequencing in families highly enriched for HTN will identify novel rare and low frequency variants associated with HTN and systolic blood pressure (SBP) with larger effect sizes.

Methods:
Exome sequencing in 150 hypertensive sib-pairs (300 subjects) and 300 unrelated controls identified 6,000 top variants which were then genotyped in SAPPHIRe families (N=1,100) and 1,100 unrelated matched controls. Single-variant analysis and four gene-based association tests (burden and SKAT tests using minor allele frequency thresholds of 1% [T1] and 5% [T5]) were performed for HTN and SBP. Bonferroni-adjusted significance level (5.4•10
-5
) was used.

Results:
Novel rare and low frequency variants with significant/suggestive association and biologic plausibility for roles in BP regulation were identified:
PLA2G4B-SPTBN5
(7 variants, burden T1 p-value 1.3•10
-6
for SBP and burden T1 p-value 4.2•10
-5
for HTN);
RGS2
(1 variant, burden T1 p-value 1.4•10
-5
for SBP and burden T1 p-value 8.9•10
-4
for HTN);
BCHE
(4 variants, burden T1 p-value 3.4•10
-5
for SBP and burden T1 p-value 5.6•10
-4
for HTN);
STRADA
(5 variants, burden T1 p-value 5.8•10
-5
for HTN);
DYNC2LI1
(8 variants, SKAT T1 p-value 9.9•10
-5
for SBP);
TNK1-PLSCR3
(8 variants, SKAT T5 p-value 3.5•10
-4
for SBP).
PLAG4B
,
BCHE
and
RGS2,
identified by both SBP and HTN analyses, are notable for roles played in the synthesis and signal transduction of vasomodulatory peptides in the vascular endothelium and vascular smooth muscle.
DYNC2LI1
and
STRADA
play roles in the regulation of renal water and salt handling via aquaporin and sodium-chloride cotransporters, respectively. Murine
PLSCR3
knock-out models lead to a metabolic syndrome phenotype in mice.

Conclusions:
Several significant and promising rare and low frequency variants associated with HTN and SBP were identified. Studies are underway to replicate the most promising loci. Identification of the causal variants for HTN may lead to novel drug targets and interventions.
Abstract 13226: Shorter Left Ventricular Ejection Time is Associated With Adverse Outcomes in Heart Failure Patients With Reduced Ejection Fraction
Authors: Patel Priyesh A , Phelan Matthew , MacKenzie Michael , Chiswell Karen , Van Dyke Melissa K , Tomfohr Jennifer , Alenezi Fawaz A , Honarpour Narimon , Velazquez Eric J
Published: April 2024

Introduction:
Worsening heart failure (HF) is thought to be associated with shorter left ventricular ejection time (LVET), but there are limited data describing the relationship between LVET and outcomes. We report the largest study to date describing the association between LVET and outcomes in an ambulatory HF population.

Methods:
We identified HF patients without significant structural or congenital heart disease who had an outpatient transthoracic echocardiogram (TTE) performed between 8/2008-7/2010 at Duke University Medical Center. We excluded patients with paced or irregular rhythms. All TTE were re-analyzed in triplicate. Multivariable logistic regression was used to evaluate the association between LVET and 1 year outcomes among HF patients with reduced ejection fraction (HFrEF) and patients with preserved ejection fraction (HFpEF).

Results:
We identified 545 HF patients (171 HFrEF, 374 HFpEF) meeting inclusion criteria. HFrEF patients were younger (median age was 60 (Quartile 1 to Quartile (Q1-Q3) 50-69) vs. 64 (Q1-Q3 53-74), with smaller proportion of females (30.4 vs. 56.4%) and similar ratio of African Americans (35.7 vs. 35.0%). Median EF among patients with HFrEF was 30% (Q1-Q3 25-35%) and with HFpEF was 54% (Q1-Q3 48-58%). There were no statistical differences in medical histories or neurohormonal therapies. Median LVET was shorter (280 vs. 315ms, p<0.001), median pre-ejection period was longer (114 vs. 89ms, p<0.001), and median relaxation time was shorter (351 vs 411ms, p<0.001) among patients with HFrEF versus HFpEF. Death or HF hospitalization occurred in 46/171 HFrEF patients and 44/374 HFpEF patients. After adjustment, longer LVET was associated with lower odds of the composite of 1 year death/1 year HF hospitalization among HFrEF patients, but not among HFpEF (Table).

Conclusion:
Longer LVET is independently associated with improved outcomes among HFrEF patients supporting a potential role for increasing LVET as a therapeutic target.
Abstract 13229: Varying ABCG1 Expression is Associated With Macrophage Apoptosis&Phagocytosis
Authors: Shen Si-Qi , Liu Fang , Wang Wei , Chen Lian-Feng , Yan Xiao-Wei
Published: April 2024

Introduction:
ATP-binding cassette transporter G1(ABCG1)is a transmembrane protein mediated efflux of cellular cholesterol to HDL, which plays a vital part in macrophage lipid homeostasis, but the role of ABCG1 in atherosclerosis still remains controversial. Our previous study demonstrated that human ABCG1 -367 G>A polymorphism in promoter region, which leads to lower ABCG1 protein expression, was associated with a reduced risk of CAD. However, the mechanism behind is not fully understood.

Hypothesis:
Oxysterols, the oxidized derivatives of cholesterol, whose efflux are mediated by ABCG1, exert cytotoxic effect on macrophage and accelerate cell apoptosis. Low ABCG1 expression induces excess oxysterols accumulation in macrophage, which augments the inflammatory response and accelerates apoptosis. Since defective apoptotic macrophage clearance in late lesions promotes atherosclerosis progression, we hypothesize that macrophage with lower ABCG1 expression may remove apoptotic cells more efficiently, thereby generating an antiatherogenic effect.

Methods:
To investigate the effect of ABCG1 expression on macrophage, we established ABCG1 knockdown cell line by means of lentivirus mediated shRNA. Apoptosis was determined by flow cytometry (FCM). Fluorescence labeled apoptotic model was generated and macrophage phagocytosis was evaluated. The inflammatory factors level and phagocytosis associated gene expression were measured by ELISA and realtime PCR.

Results:
Compared with control group, macrophage with lower ABCG1 expression had a higher secretion level of Inflammatory factors, such as TNF-α and IL-1β, showing an increased expression of classic inflammatory M1 phenotype markers,such as CD86 and TGF-β, and a down-regulation of CD163,Arg and IL-6 expression, which are markers of anti-inflammatory M2 phenotype macrophage. The apoptosis was significantly accelerated and the phagocytic clearance was enhanced after ABCG1 expression decreased, which means apoptotic cells could be removed more quickly. Both CD36 and Mertk showed a higher mRNA level in ABCG1 knockdown group.

Conclusions:
Decreased expression of macrophage ABCG1 may exert antiatherogenic function through accelerating apoptosis and enhancing phagocytosis.
Abstract 13384: Prognosis of Patients With Myocardial Infarction With Non-Obstructive Coronary Arteries as Compared With Obstructive Coronary Disease
Authors: Dreyer Rachel P , Tavella Rosanna , Curtis Jeptha P , Wang Yongfei , Pauspathy Sivabaskari , Messenger John , Rumsfeld John S , Maddox Thomas M , Krumholz Harlan M , Spertus John A , Beltrame John F
Published: April 2024

Introduction:
The prognosis of patients with Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) is poorly understood. We examined the prevalence of adverse events (mortality, re-infarction and readmission) in patients with MINOCA over 1 year versus patients with acute myocardial infarction (AMI) and obstructive coronary artery disease (MICAD).

Methods:
Between July 2009 and December 2010, both patients with STEMI and NSTEMI, aged >65 years, from the National Cardiovascular Data Registry (NCDR

®

) CathPCI Registry were classified as having either obstructive or non-obstructive CAD (n=570,219) on the basis of their angiographic reports revealing no epicardial vessel with stenosis ≥50% (MINOCA) or at least one stenosis ≥50% (MICAD). Re-hospitalizations, repeat AMI, and mortality were assessed via linkage to Medicare data. We had the following exclusion criteria: (a) patients presenting with cardiac arrest within 24 hours (n=3,510), (b) patients with AMI as a complication during hospitalization (n=1,751), and (c) patients not in the Medicare data, or that could not be matched with Medicare through the patient beneficiary ID and discharge date (n=469,722). Analyses comparing MINOCA and MICAD were performed using the chi-squared test for categorical variables and the T-test for continuous variables.

Results:
Among 95,236 AMI patients, 4,831 patients (5.1%) had MINOCA. Compared to those with MICAD, patients with MINOCA were younger (75±7 vs 76±7, P<0.001), more likely to be female (78% vs 42%, P<0.001), and were predominately white (89% vs 91%, P<0.001). Outcomes over 1 year are described in the Table.

Conclusion:
In an elderly AMI population, the occurrence of MINOCA accounts for 5% of AMI presentations. Although MINOCA patients had fewer adverse events over 1 year compared with MICAD patients, they remain at modest to high risk for readmission and mortality. Further studies are needed to define whether or not these events are preventable.
Abstract 13416: The Days of the Holter Monitor Are Numbered: Extended Continuous Rhythm Monitoring Detects More Clinically Significant Arrhythmias in Adults With Congenital Heart Disease
Authors: Schultz Karen , Lui George , McElhinney Doff , Fernandes Susan , Dubin Anne , Rogers Ian , Viswanathan Mohan , Romfh Anitra , Motonaga Kara , Ceresnak Scott
Published: April 2024

Introduction:
Arrhythmias are a leading cause of death in adults with congenital heart disease (ACHD). Arrhythmia detection is essential to management and risk assessment in ACHD. While 24 to 48-hour Holter monitors are often used to assess arrhythmia burden, extended continuous rhythm monitors (ECRM) can record 2 weeks of data. We hypothesized that more clinically significant arrhythmias would be detected on ECRM beyond the first 48 hrs of monitoring.

Methods:
We reviewed ambulatory Zio® (iRhythm, San Francisco, CA) monitors performed in ACHD patients from June 2013 - May 2016. Atrial fibrillation/flutter (AF), ventricular tachycardia (VT), supraventricular tachycardia (SVT), sinus pause >3 sec, and 3
rd
or 2
nd
degree type II atrioventricular block (AVB) were considered significant. Number and type of arrhythmias detected within the first 48 hrs were compared to those identified beyond 48 hrs.

Results:
A total of 387 monitors were performed in 306 patients (34 ± 12.5 yrs, 40% male). The most common diagnoses were Tetralogy of Fallot, transposition of the great arteries, and single ventricle after Fontan. Average wear time was 9.4 ± 4.2 d. Overall, 51% of ECRM showed a significant arrhythmia, fewer than half of which were noted during the first 48 hrs (25% overall). VT was detected by ECRM in 17%, only 30% of which were within 48 hrs. SVT was detected by ECRM in 40%, 48% of which were within 48 hrs. Kaplan-Meier estimates of freedom from arrhythmia are shown in the table and figure.

Conclusion:
ECRM was more likely to detect a significant arrhythmia beyond the standard 48-hour monitoring period in ACHD patients, suggesting that ECRM may be more useful than Holter monitoring in this population.
Abstract 13441: The QTc Interval Does Not Predict Mortality at the Emergency Department
Authors: Vandenberk Bert , Siau Caroline , Vandael Eline , Foulon Veerle , Verelst Sandra , Willems Rik
Published: April 2024

Introduction:
The Bazett corrected QT interval (QTcB) has been shown a predictor of outcome at the Emergency Department (ED). Since the known limitations of QTcB at higher heart rates, we investigated the use of a recently proposed QRS width dependent QTc algorithm (QTcA) at the ED.

Methods:
We performed a retrospective age- and sex-matched cohort study, powered to detect mortality differences between normal and prolonged (> 450/470 ms in men and women respectively) QTcB at the ED. QTcA, Fridericia formula is used when QRS<120ms and Rautaharju when ≥120ms, was compared with QTcB. Cox regression modeling for in-hospital mortality was performed.

Results:
In total 1930 patients, age 72 ± 16 y, 63% male and mean triage code 2.5 ± 0.6, were included. The mean heart rate was 81 ± 22 bpm. 18% patients had a QRS duration ≥120ms and 81% had sinus rhythm. In-hospital mortality was 4.4% and 1 y mortality was 19.5%.

Using QTcB, 50% of patients had prolonged QTc, whereas only 17.4% using QTcA. In-hospital mortality in the prolonged QTcB group was significantly higher (6.0%) compared to the control group (2.8%, p<0.001), whereas with QTcA mortality rates were similar (5.4% vs 4.2% respectively, p=0.349). Also, 1 y mortality was significantly higher in patients with prolonged QTcB (22.6% vs 16.4%, p=0.001), while prolonged QTcA showed only a trend to worse survival (22.9% vs 18.8%, p=0.080).

In univariate Cox regression for in-hospital mortality, QTcB was a predictor of mortality (HR 1.004, 95%CI 1.000 - 1.009), while QTcA was not (HR 1.001, 95%CI 0.995 - 1.008).

After multivariate analysis QTcB did not remain as independent predictor of mortality. Independent predictors were heart rate (HR 1.02, 95%CI 1.01-1.03), history of cardiovascular disease (HR 1.66, 95%CI 1.00-2.76), witnessed arrhythmia requiring CPR (HR 3.79, 95%CI 1.66-8.67), neurological events (CVA, epileptic insult, IC bleeding or hematoma) (HR 3.51, 95%CI 1.91-6.43), age-adjusted Charlson Comorbodity Index (HR 1.18, 95%CI 1.10-1.27), lower eGFR (HR 0.99, 95%CI 0.98-1.00) and higher leukocyte count (HR 1.02, 95%CI 1.01-1.03).

Conclusion:
Several easily obtainable parameters and risk factors can be useful for risk stratification at the ED, however adequate corrected QT was not an independent predictor of mortality.
Abstract 13476: Usefulness of Dual Induction Tests for Coronary Artery Spasm and Lethal Ventricular Arrhythmias in Patients Surviving Out-of-Hospital Cardiac Arrest
Authors: Komatsu Masayasu , Takahashi Jun , Nakano Makoto , Kondo Masateru , Tsuburaya Ryuji , Hao Kiyotaka , Nishimiya Kensuke , Nihei Taro , Matsumoto Yasuharu , Ito Kenta , Fukuda Koji , Shimokawa Hiroaki
Published: April 2024

Background:
It remains to be established how to treat patients with out-of-hospital cardiac arrest (OHCA) without significant organic heart disease, especially regarding the use of implantable cardioverter-defibrillator (ICD). Among the possible causes of OHCA, coronary artery spasm (CAS) and lethal ventricular arrhythmias (VAs) are important causes of the disorder.

Methods and Results:
In 47 consecutive OHCA survivors without organic heart disease who had fully recovered (M/F 44/3, 43±13 yrs.), we performed dual induction tests for CAS and VAs. We first performed acetylcholine provocation test with subsequent calcium channel blocker-based antianginal medications and then performed ventricular fibrillation (VF) induction test with programmed stimulation at an interval of 1~2 weeks. ICD was implanted in all patients. According to the results of the dual induction tests, we divided them into 4 groups; CAS-alone (n=7), VAs-alone (n=13), both-positive (n=24), and both-negative (n=3) (
Figure A
). Among the 4 groups, no significant difference was noted in the factors that could influence the development of VF, such as QTc, late potential, familial history of sudden cardia death, or serum levels of electrolytes. During a median follow-up of 38 months, VF recurred in all groups except the both-negative group, of which 13 cases had appropriate ICD shocks to terminate fatal VAs. When we analyzed the 16 patients with Brugada-like ECG pattern (34%) separately, no VF episode was noted in the CAS-alone or both-negative group throughout the study period. Kaplan-Meier analysis showed that the CAS-alone group was at lower risk for OHCA recurrence as compared with the Brugada syndrome group (log-rank test, P=0.036) (
Figure B
).

Conclusions:
These results indicate that among OHCA survivors, those with CAS-alone and without Brugada syndrome in the dual induction tests may be at low risk for recurrent sudden death and ICD firing.
Abstract 13478: Increased Changes in Calculated Plasma Volume Predict Poor Prognosis in Heart Failure
Authors: Chishinga Nathaniel , Bilchick Kenneth , Smith LaVone , Parker Alex , Zhuo David , Mazimba Sula
Published: April 2024

Introduction:
Plasma volume (PV) is contracted in stable patients with heart failure (HF) due to the effects of therapy aimed at reducing congestion, while increased PV can complicate the progression of HF. We sought to determine the prognostic implications of calculated PV in patients with HF.

Hypothesis:
Increased changes in PV predict mortality after hospital discharge in HF patients.

Methods:
We used data from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial for our analysis. The outcome in our study was all-cause mortality after hospital discharge. We used the hemoglobin and 1-hematocrit method to calculate the percentage change in PV (%ΔPV) between baseline and hospital discharge. We used Kaplan-Meier curves to compare 180-day (6-month) survival for patients that had increased %ΔPV to patients that had reduced or no %ΔPV. We used Cox proportional hazard regression analysis to adjust for age and gender, and obtained adjusted hazard ratios (AHR) and 95% confidence intervals (CI) of the association between mortality and %ΔPV.

Results:
There were 315 patients with complete data on PV that were included, of which 231 (73.3%) were men. The mean age was 56 years (range: 22-88 years). Of these 315 patients, 59 (18.7%) died after discharge during 4365.3 person days (PDs) of observation from baseline; mortality incidence rate was 1.4 deaths/100 PDs. Patients with reduced or no %ΔPV were more likely to survive than those with increased %ΔPV at the end of follow-up (Log rank test p=0.0042). Patients with increased %ΔPV had a statistically significant increased risk of mortality compared to patients with reduced or no %ΔPV (AHR 1.9, 95% CI: 1.1-3.2).

Conclusions:
Increased changes in calculated plasma volume predicted 6-month mortality in HF patients enrolled in the ESCAPE trial. Plasma volume changes during hospitalization for acute decompensated HF could guide risk stratification and prognosis in HF patients.
Abstract 13729: Significant Prognostic Values of Acute Preload Stress Echocardiography by Using Leg-positive Pressure Maneuver in Patients With Severe Aortic Stenosis
Authors: Matsuzoe Hiroki , Matsumoto Kensuke , Tanaka Hidekazu , Takada Hiroki , Soga Fumitaka , Hatani Yutaka , Hatazawa Keiko , Shimoura Hiroyuki , Ooka Junichi , Sano Hiroyuki , Ryo-Koriyama Keiko , Hirata Ken-ichi
Published: April 2024

Introduction:
Recently, leg-positive pressure (LPP) maneuver, using customized air-bags inflated both lower limbs to maintain a constant loading pressure (90 mmHg for 5 minutes), is reported to be able to apply acute preload stress non-invasively without significant change in either heart rate or blood pressure.

Hypothesis:
We hypothesized the ability to utilize the Frank-Starling mechanism without significant increase in left ventricular (LV) filling pressure in response to LPP stress could provide additional prognostic capability for patients with aortic stenosis (AS).

Methods:
We prospectively recruited 48 patients with severe AS. LV stroke volume (SV) was assessed by means of pulsed-wave Doppler, and then normalized by body surface area (SVi). The ratio of transmitral E wave and mitral annular velocity (e’) was calculated to estimate LV filling pressure. These parameters were obtained both at rest and during LPP stress. Event-free survival was then tracked for 136 days.

Results:
Eight patients developed adverse cardiac events. During acute preload stress, forward SV increased significantly (SVi : 42±9 to 48±9 ml/m
2
, p<0.001) along with minimal change in LV filling pressure (E/e’: 20±8 to 21±11, n.s.) in patients without cardiac events. On the other hand, Frank-Starling mechanism was significantly impaired (SVi: from 41±10 to 38±8 ml/m
2
), while LV filling pressure increased to the critical level (E/e’:26±7 to 33±7, p<0.01) in patients with cardiac events. When the patients were divided into two subgroups based on the response to LPP stress, patients without preload reserve (ΔSVi<5ml/m
2
) showed worse event rate than the others (p<0.05). Similarly, patients without diastolic reserve (ΔE/e’ ratio >3) exhibited significantly worse event-free survival (p<0.05).

Conclusions:
Assessment of preload reserve and diastolic reserve during LPP stress can enhance the predictive capability for cardiovascular outcomes events for patients with AS.
Abstract 13846: Telephone CPR is Independently Associated With an Increase in Initial Shockable Rhythms in Patients With Out-of-Hospital Cardiac Arrest
Authors: Panczyk Micah , Sutter John , Langlais Blake , Hu Chengcheng , Vadeboncoeur Tyler F , Mullins Terry , Spaite Daniel W , Bobrow Bentley J
Published: April 2024

Background:
Bystander CPR (BCPR) and telephone CPR (TCPR) are associated with improved OHCA outcomes. It has been shown that BCPR increases the proportion of patients with an initial shockable cardiac rhythm (VF/VT) when encountered by EMS. It is unknown whether TCPR does the same.

Objective:
To assess whether TCPR is independently associated with an increase in initial shockable cardiac rhythms during OHCA.

Methods:
Data from 9-1-1 audio recordings, first care EMS reports and hospital records were linked for OHCAs of presumed cardiac origin (1/2011-12/2014). Three cohorts were analyzed: TCPR, BCPR or no CPR. Using no CPR as the reference group, we assessed whether TCPR and BCPR were independently associated with initial shockable rhythms in a logistic regression model controlling for gender, event location, witness status and EMS response interval.

Results:
After exclusions, 2715 adult OHCA events with linked outcome data were analyzed (median age: 63; male: 66.8%; 33.3% witnessed arrest). Median response interval was 5 min. The BCPR rate (lay rescuer CPR
without
telephone instructions) was 24.8% and survival in this group was 15.4%. The TCPR rate (lay rescuer CPR with telephone instructions) was 40.2% and survival in this group was 11.7%. For the no-CPR group, 20.5% had an initial shockable rhythm. For the BCPR group, 34.6 % had an initial shockable rhythm. For the TCPR group, 23.2% had an initial shockable rhythm. Provision of BCPR and of TCPR were each independently associated with shockable rhythms [aOR (BCPR) = 1.7, 95% CI: 1.33-2.17, p=0.0001; aOR (TCPR) = 1.3, 95% CI: 1.04-1.63, p=0.0001].

Conclusion:
The provision of both BCPR and TCPR were independently associated with an increased rate of initial shockable cardiac rhythms and an increase in survival to hospital discharge compared to no CPR.
Abstract 13860: Patient and Partner (P+P) Intervention to Improve Outcomes After and Implantable Cardioverter Defibrillator (ICD): Three Month Physical Health Outcomes
Authors: Dougherty Cynthia M , Thompson Elaine A , Dobra Adrian , Kudenchuk Peter J
Published: April 2024

Introduction:
Partners of patients who get an ICD play a pivotal role in the patient’s adjustment over the initial 3 months. The purpose of this study was to compare 2 intervention programs after an initial ICD: an intervention for the patient-only (P) was compared to an intervention involving both the patient and their intimate partner (P+P).

Hypothesis:
The P+P intervention will demonstrate better patient reported outcomes than the (P)-only intervention.

Methods:
A prospective randomized control trial (RCT) comparing 2 interventions after an initial ICD on patient and partner outcomes, was conducted with 301 intimate couples in the Pacific NW. The self-efficacy based nurse telephone intervention was delivered over the 1
st
12 weeks following ICD implant for primary (60%) or secondary (40%) prevention. Patient physical health outcomes were measured at baseline hospital discharge and 3 months later using the Patient Concerns Assessment (PCA), SF-36 PCS, total steps taken on a Step Watch physical activity monitor, and the Sudden Cardiac Arrest Self-Efficacy (SCA-SE) scale. Structural equation modeling was used to test the hypothesized effects of the intervention and the mediating effects of self-efficacy on patient physical health.

Results:
ICD patients (N=150) in P-only were (mean±SD) 65.0±12.3 years old, 90.1% Caucasian, 70.2% were male, with Charlson scores of 2.26±1.4, EF% 33.8±13.5, & household income $30-49,000 (23%). ICD patients (N=151) in P+P were 63.3±12.5 years old, 92% Caucasian, 77.3% were male, with Charlson scores of 2.2±1.5, EF% 34.4±15.2. From baseline to 3 months, PCA symptoms were reduced in both groups p=0.84, and SF-36 physical health (p=0.62) and total steps/day (p=0.26) improved in both groups. The direct effect of the intervention on patient self-efficacy at 3 months was significant (
B
=0.11, p=0.03). Improvements in patient self-efficacy were associated with a reduction in 3 month physical symptoms (
B
=-0.19, p<0.001), and improved physical health (
B
=0.16, p<0.001), but not total steps/day (
B
=0.07, p=0.07). Fit indicies met standards for model fit: CFI=0.90, RMSEA=0.08.

Conclusions:
The intervention arm involving the partner (P+P) resulted in higher levels of patient physical health after an initial ICD.