bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12054: Electro-anatomic Mapping Guided Endomyocardial Biopsy: A Systematic Review
Authors: Vaidya Vaibhav , Deshmukh Abhishek , Vasudevan Krithika , Farrell Ann , Cooper Leslie , Kapa Suraj , Noseworthy Peter , Packer Douglas , Asirvatham Samuel
Published: April 2024

Introduction:
Electro-anatomic mapping (EAM) has been studied as a modality to improve the sensitivity and reduce false negative rates with endomyocardial biopsy (EMB). We systematically reviewed the literature describing EAM guided EMB.

Methods:
An experienced librarian developed search strategies for Ovid MEDLINE, Ovid Embase, Ovid CDR, Cochrane Central, Scopus and Web of Science. There were no restrictions on language or publication date. Animal studies were excluded. Search strategy included MESH headings and keywords including endomyocardial biopsy and electroanatomic mapping.

Results:
Out of 139 studies initially identified, 16 (9 case series, 7 case reports) were included in this systematic review. EAM guided EMB was performed in 152 patients and results of 241 biopsies were available for analysis. The most common indications for EAM guided EMB were suspected arrhythmogenic right ventricular cardiomyopathy (ARVC), myocarditis and cardiac sarcoidosis (CS). While fluoroscopic visualization of the bioptome close to mapping catheter was the most commonly utilized biopsy technique (n=7 studies), direct visualization of bioptome on CARTO (n=4) and on NavX (n=2) were used as well. Low voltage areas had abnormal myocardial histology more commonly (range 60-100%) than normal voltage areas (range 11-52%). Sensitivity of low voltage areas for abnormal myocardium ranged from 60% to 82%. EAM guided EMB appears safe and adverse events were noted in only one study (remote hemopericardium).

Conclusions:
EAM guided EMB is a safe and efficacious method to improve the sensitivity and reduce the false negative rate of conventional fluoroscopy guided biopsy.
Abstract 12090: Seattle Heart Failure Model and Seattle Proportional Risk Model Together Identify Patients Most Likely to Benefit From Primary Prevention ICDs - An NCDR Analysis
Authors: Bilchick Kenneth C , Cheng Alan , Wang Yongfei , Curtis Jeptha , Dharmarajan Kumar , Levy Wayne
Published: April 2024

Introduction:
Risk models are greatly needed to target appropriate patients for implantable cardioverter defibrillators (ICDs) in clinical practice for primary prevention of sudden death.

Hypothesis:
We hypothesized that the Seattle Heart Failure Model (SHFM) for overall survival and the Seattle Proportional Risk Model (SPRM) for proportional risk of arrhythmic death (AD) would identify National Cardiovascular Data Registry (NCDR) ICD Registry patients most likely to have improved survival with versus without an ICD.

Methods:
SHFM and SPRM scores were determined for patients with and without ICDs (ICD Registry versus a control group derived from the University of Washington Registry, Italian Heart Failure Registry, Swedish Heart Failure Registry, COMET, Val-HeFT, and PRAISE trials). Multivariable Cox proportional hazards regression was used to evaluate adjusted associations of SPRM and SHFM with survival over 5 years from the Social Security Death Index.

Results:
Among 98,846 patients (87,914 with ICDs and 10,932 without ICDs), increasing SFHM risk was strongly associated with decreased survival (P<0.0001). Compared with patients having a lower SPRM-predicted proportional risk of AD, patients with a higher predicted proportional AD risk had approximately twice the ICD survival benefit (HR 0.602 [95% CI 0.537-0.675] for SPRM quintile 5 versus HR 0.793 [0.736-0.855] for SPRM quintile 1). The ICD-SPRM interaction was highly significant (Figure). The ICD did not improve adjusted survival versus controls in the 25% of patients with higher predicted survival (SHFM < mean) but a lower proportional AD risk (SPRM < mean) (HR 0.921, 95% CI 0.787-1.08, P=0.31); however, survival in patients with opposite findings (SHFM > mean, SPRM > mean) was greatly improved versus controls (HR 0.599, 95% CI 0.530-0.677, P<0.0001).

Conclusions:
The SHFM and SPRM scores together identify real-world patients most likely to benefit from primary prevention ICD implantation.
Abstract 12207: NEDD9 Cysteinyl Thiol Oxidation Impairs NEDD9 Binding by Smad3 to Increase Pulmonary Endothelial Matrix Metalloproteinase-2 Proteolytic Activity
Authors: Stephens Thomas E , Samokhin Andriy , Arons Elena , Gladyshev Vadim N , Marino Stefano M , Loscalzo Joseph , Lepold Jane A , Maron Bradley A
Published: April 2024

In pulmonary arterial hypertension (PAH), endothelial dysfunction due to increased oxidant stress induces adverse vascular remodeling. In cancers that share overlap with PAH pathobiology, the CAS-L protein NEDD9 upregulates the remodeling enzyme MMP-2. Clearance of NEDD9 requires Smad3 binding to its protein-docking site, which includes Cys18. We hypothesized that NEDD9 Cys18 oxidation impairs NEDD9-Smad3 binding to increase NEDD9 and MMP-2 activity in pulmonary artery endothelial cells (PAECs). To test this hypothesis, cells were treated with hydrogen peroxide (H
2
O
2
) (250 μM) for 2.5, 5.0, and 7.5 min and NEDD9 levels were assessed by immunoblot. Compared to time 0, H
2
O
2
increased NEDD9 levels by 2.4-, 2.5-, and 3.1-fold, respectively (P<0.05). Next, structural homology to NEDD9 was modeled after 1wyx, 2181, and 3t6g, and the pKa and accessible surface area (ASA) of 10 putative Cys sulfur atoms was analyzed. By this approach, Cys18 (pKa=6.65; ASA=17.5 Å
2
) was predicted as the most reactive cysteinyl thiol. Mass spectrometry performed on in-gel trypsin digested samples of immunoprecipitated NEDD9 from PAECs treated with H
2
O
2
(500 μM) for 20 min confirmed Cys18 oxidation to cysteinyl sulfonic acid. To determine if Cys18 oxidation was associated with changes in NEDD9-Smad3 binding, PAECs were treated with vehicle (V) control, the pro-oxidant hormone aldosterone (ALDO) (10
-7
mol/L) for 24 hr, or H
2
O
2
(500 μM) for 20 min and immunoprecipitated using an antibody to the Cys18 region of NEDD9. Anti-cysteine sulfenic acid (R-SOH) immunoblotting showed that compared to V-treated cells, ALDO and H
2
O
2
increased NEDD9-SOH levels by 54% and 73%, respectively (P<0.04). In turn, increased NEDD9-SOH induced by ALDO or H
2
O
2
decreased NEDD9-Smad3 binding by 64% (P=0.08) and 87% (P<0.01), respectively. Compared to V-treated cells, ALDO also increased MMP-2 proteolysis by zymography (184 ± 4.9 vs. 248 ± 11 a.u., P<0.01), which was inhibited by 38% (P<0.05) in ALDO-treated cells transfected with si-NEDD9. Oxidative modification of NEDD9 Cys18 is a novel molecular mechanism regulating NEDD9 in PAECs in vitro. Identifying NEDD9 Cys18 as a novel target to inhibit endothelial remodeling proteins may have important therapeutic implications for patients with PAH.
Abstract 12224: Electrocardiographic Beat-to-Beat QT Interval is affected by Phases of Respiration: The Atherosclerosis Risk in Communities Study
Authors: Kabir Muammar M , Sedaghat Golriz , Thomas Jason , Waks Jonathan W , Sitlani Colleen M , Biggs Mary L , Sotoodehnia Nona , Siscovick David S , Post Wendy S , Henrikson Charles A , Solomon Scott D , Soliman Elsayed Z , Buxton Alfred E , Josephson Mark E , Tereshchenko Larisa G
Published: April 2024

Introduction:
Respiration causes changes in heart rate and autonomic tone. The effect of electrocardiographic (ECG) RR interval (RRI) on QT interval (QTI) is well described, but correction of QTI for RRI has limitations.

Hypothesis:
We hypothesized that respiration affects QTI independently from its effect on RRI, and that this effect is different in sudden cardiac death (SCD) victims vs. those without SCD.

Methods:
We prospectively analyzed 10 second 12-lead ECGs containing only sinus beats in 14908 participants including those who succumbed to SCD during median 14 years of follow-up (n=272; age:56±6y; 39% female; 55% white) in The Atherosclerosis Risk in Communities (ARIC) study. Respiration effect was derived from magnitude changes in QRS loops on vectorcardiograms derived from 12 lead ECGs. Panel time-series regression models were used. Time series of RRI and change in respiratory phase (RPH), magnitude and RR angle served as patient-specific random effect predictors. Age, sex and race were entered as fixed effect predictors. QTI time series served as an outcome.

Results:
In healthy ARIC participants with no history of coronary heart disease (CHD), heart failure, stroke, hypertension, diabetes, smoking, or bundle branch block (n=10,553; age:53±6y; 71% female; 81% white), the relationship between QTI and RPH (adjusted for RRI and demographics) was direct: 1 radian RPH

increase

was associated with a 5.2 ms

increase

in QTI (95%CI 0.78 - 9.63; P=0.021). QTI and RPH showed inverse relationships in SCD victims: 1 radian

decrease

in RPH was associated with a 99.9 ms

increase

in QTI (95%CI 26.7 - 173.2 ms; P=0.008) in

CHD SCDs

(n=28; age:57±6y; 34% female; 66% white) as compared to no effect in

non-CHD SCDs

(n=146; age:54±7y; 34% female; 100% white): +16.1 (95%CI -17.3 to 49.5 ms; P=0.344) QTI.

Conclusion:
Respiration affects QTI independently from its effect on RRI, and differently in SCD victims compared to healthy individuals. Correction of QTI should include both RRI and RPH.
Abstract 12228: Understanding the Gender Gap in Patients Undergoing Atrial Fibrillation Ablation: Women Delay Ablation Until Functionally Limited and Symptoms Are Severe
Authors: Bolger Lauren E , Mandavilli Amith , Sears Samuel F , Hummel James P , Chung Eugene H , Mounsey J P , Gehi Anil K
Published: April 2024

Introduction:
The incidence of atrial fibrillation (AF) is nearly equivalent in men and women. Yet, existing literature indicates a gender gap in patients with atrial fibrillation presenting for ablation. We examine this discrepancy among patients undergoing AF ablation at The University of North Carolina hospital.

Hypothesis:
We hypothesized that gender differences in AF symptoms and functional capacity could account for the gender gap in patients undergoing AF ablation.

Methods:
A study of 178 consecutive patients presenting for AF ablation was conducted between October 2014 and May 2015. Prior to undergoing ablation, consenting patients completed the Duke Activity Status Index (DASI) evaluating functional capacity and the Atrial Fibrillation Effect on Quality-of-Life Questionnaire Tool (AFEQT) assessing AF-specific quality of life, symptom severity, treatment concern, and daily activities. Questionnaire data was analyzed with baseline demographics and comorbidities for gender differences.

Results:
Of 178 patients completing the baseline questionnaire, the proportion of men pursuing ablation (n=129, 72.5%) largely outweighed that of women (n=49, 27.5%). There were no gender differences in baseline demographics with the exception of significantly higher prevalence of obstructive sleep apnea (p<0.001) and persistent AF in men (p<0.05). Women presented for AF ablation with significantly lower functional capacity (p<0.001), higher AF symptom severity (p<0.05) and lower overall AF quality of life (p<0.05) in comparison to men (Table).

Conclusions:
Our findings suggest that women do not present for AF ablation until symptoms are severe and functional capacity is low, likely contributing to the gender gap in AF ablation referrals. Whether this disparity is due to patient or provider factors requires further evaluation. Education of patients and providers regarding the potential efficacy and risks of ablation may help to bridge this gender gap.
Abstract 12526: Snf1-related Kinase Improves Cardiac Mitochondrial Efficiency by Decreasing Mitochondrial Uncoupling
Authors: Rines Amy K , Chang Hsiang-Chun , Wu Rongxue , Sato Tatsuya , Khechaduri Arineh , Shapiro Jason S , Shang Meng , Burke Michael A , Jiang Xinghang , Chen Chunlei , Rawlings Tenley A , Lopaschuk Gary D , Schumacker Paul T , Abel E. D , Ardehali Hossein
Published: April 2024

Introduction:
Ischemic heart disease limits oxygen and metabolic substrate availability to the heart, resulting in cardiac tissue death. Snf1-related Kinase (SNRK) is a serine/threonine kinase with sequence similarity to AMP-activated protein kinase, but its function is unknown. We found that SNRK is increased in hearts from patients with ischemic cardiomyopathy, and our gene array data suggested that SNRK alters metabolic genes. Here, we assessed the hypothesis that SNRK improves cardiac metabolic efficiency and mitochondrial uncoupling, and protects against ischemia/reperfusion (I/R) injury.

Results:
Cardiac-specific SNRK transgenic (TG) mice displayed decreased glycolysis, glucose oxidation, and palmitate oxidation compared to wild type littermate controls in perfused working hearts. However, cardiac power, contractility, ATP, and triglyceride and glycogen stores were maintained, while oxygen consumption was reduced, demonstrating that SNRK TG mice have increased cardiac metabolic efficiency. Consistent with improved cardiac metabolic efficiency, SNRK TG mice exhibited decreased infarct size after I/R. Mitochondria from SNRK TG mice also had reduced respiration, and increased respiratory control ratio and mitochondrial membrane potential, indicating reduced mitochondrial uncoupling. Uncoupling protein 3 (UCP3) levels were also decreased. Conversely, hearts from heterozygous SNRK knockout mice had increased glucose and palmitate oxidation and UCP3. SNRK knockdown in cardiac cells decreased mitochondrial efficiency, which was abolished with UCP3 knockdown. To determine the mechanism for the regulation of UCP3 by SNRK, we performed yeast two-hybrid assay, and identified tribbles homolog 3 (Trib3) to bind to SNRK. Furthermore, Trib3 enabled downregulation of UCP3 by downregulating the expression of PPARα.

Conclusions:
Our results demonstrate that overexpression of SNRK decreases cardiac metabolic substrate usage and oxygen consumption but maintains cardiac function and enhanced mitochondrial coupling. We also identify a binding partner of SNRK, Trib3, which is upregulated by SNRK in mice and mediates the regulation of PPARα and UCP3 by SNRK.
Abstract 12577: Markers of Residual Risk in Type 2 Diabetes and Stable Ischemic Heart Disease: Insights From the BARI 2D Trial
Authors: Everett Brendan M , Brooks Maria , Vlachos Helen E , Chaitman Bernard , Frye Robert , Bhatt Deepak L
Published: April 2024

Background:
In spite of aggressive preventive therapy, patients with type 2 diabetes (T2D) and stable ischemic heart disease (SIHD) remain at high risk for major cardiovascular events and death. Understanding the pathophysiologic determinants of that residual risk could help identify effective preventive therapies.

Methods and Results:
In this Ancillary Study of the BARI 2D trial, we examined the predictive value of biomarkers from 6 distinct pathophysiologic pathways in 2285 men and women with T2D and SIHD who were followed for a median (IQR) of 5.0 (4.1-6.0) years. The endpoint for this Ancillary Study was a composite of myocardial infarction, stroke, heart failure, or all-cause mortality. The 5-year Kaplan-Meier event rate was 31%. The pathophysiologic processes evaluated included dysglycemia (HbA1c), dyslipidemia (LDL-C), myocardial strain (NT-proBNP), myocardial injury (high-sensitivity cardiac troponin T [hsTnT]), subclinical inflammation (high-sensitivity C-reactive protein [hsCRP]), and nephropathy (presence/absence of macroalbuminuria). In Cox proportional hazards models adjusted for baseline risk factors, angiographic severity of disease, and ejection fraction, each marker except LDL-C was a significant predictor of outcome (Figure) in this population with 74% baseline statin use. After mutual adjustment for all 6 markers and baseline risk factors, the hazard ratio (95% CI) per 1-SD of natural logarithm transformed concentration was largest for NT-proBNP [1.29 (1.17, 1.42)], followed by hsTnT [1.16 (1.07, 1.26)], HbA1c [1.12 (1.03, 1.21)], and hsCRP [1.11 (1.03, 1.20). Macroalbuminuria was not a significant predictor after adjustment for the other markers (Figure).

Conclusions:
In this high-risk population of patients with type 2 diabetes and stable ischemic heart disease, strategies to target myocardial strain, myocardial injury, and subclinical inflammation may lead to improvements in cardiovascular outcome.
Abstract 12589: Delayed Therapeutic Hypothermia Protects Against the Myocardial No-reflow Phenomenon Independent of Infarct Size in a Rat Ischemia/reperfusion Model
Authors: Dai Wangde , Kloner Robert A
Published: April 2024

Background:
Adjunctive therapy in addition to reperfusion to reduce myocardial infarct size has been disappointing based on clinical trials. New therapeutic targets independent of infarct size modification are needed. No-reflow predicts poor clinical outcome. In this study, we investigate the effects of a single application of delayed (post-reperfusion) therapeutic hypothermia (TH) on no-reflow in rats.

Methods:
Rats were subjected to 60 min of coronary artery occlusion followed by 3 hours of reperfusion. Rats were divided into normothermic (n=5) and TH (n=5) groups. In the TH, hypothermia was initiated at 1 minute after coronary artery reperfusion by pumping room-temperature (22 °C) saline into and out of the thoracic cavity for 1 hour. This decreased intra-thoracic temperature to around 27 °C within a few minutes. At 3 hours after reperfusion, hearts were excised for infarct size (tetrazolium staining) and no-reflow zone (Thioflavin S technique) measurement.

Results:
Ischemic risk area (expressed as % of LV area, assessed by blue dye technique) was 52.4 ± 2.9% in normothermic group and 44.8±3.7% in TH group (p=0.15). Infarct size (expressed as % of risk area) was similar between normothermic (73.8 ±3.8% ) and TH (72.0± 4.0%, p = 0.76) groups. No-reflow area (expressed as % of risk area) was significantly reduced in TH group (18.0 ± 4.4%) compared with normothermic group (39.5 ± 2.9%, P = 0.005). When expressed as % of necrotic area, no-reflow area was reduced by more than half in TH group (25.5 ± 6.4%) versus in normothermic group (54.4 ± 5.3%, P = 0.01).

Conclusions:
A single delayed TH markedly diminishes reperfusion induced microvascular damage and no-reflow even when initiated after reperfusion, and independent of infarct size.
Abstract 12706: Novel Correlates of Depressive Symptoms in Family Caregivers of Heart Failure Patients
Authors: Dunbar Sandra B , Corwin Elizabeth , Gary Rebecca A , HIggins Melinda K , Smith Alicia , Butler Javed
Published: April 2024

Introduction:
Family Caregivers (FCGs) of persons with heart failure (HF) often experience depressive symptoms. Greater understanding of associated factors is essential to direct HF FCG interventions.

Purpose:
This study examined correlates of depressive symptoms in FCGs of HF patients including individual factors, caregiving demands, family context, and genotype (serotonin transporter-linked polymorphic region [5-HTTLPR]) associated with a predisposition to depression.

Methods:
HF FCGs (n=127; mean age 55.3 ± 11.5 years, 92% women, 58% African American) were recruited. Measures were: demographics, family functioning (FAD), caregiving demands (Oberst Caregiving Demands, caregiver strain [CS], caring for others), sleep quality (PSQI) and depressive symptoms (CES-D). In a subsample (n= 82), 5-HTTLPR genotype was determined. Analyses included correlations and regression models for the full sample and the 5-HTTLPR genotype allele groups (XL/L, any S) separately.

Results:
Mean CES-D scores were 15.2 ± 10.4; 41.7% scored > 16 indicating depressive symptoms. Bivariate correlations (p<.05) were found between CES-D scores and caring for others, FAD, mental and physical CS, and Oberst and PSQI scores. Regression models accounted for 42.7% (F
5,106
=17.55, p<.001) of the variability in CES-D scores with PSQI (p<.001), Oberst (p=.006), FAD (p=.005), caring for others (p=.003), and race (p=.01) retained as predictors. In the 5-HTTLPR analyses of the XL/L group, only FAD and PSQI were associated with CESD (n=42; adjR
2
=.339, F(
2,39
)=11.527, p<.001). For the any S allele group, caring for others, and strain were associated with depressive symptoms (n=40; adjR
2
=.54, F (
3,46
)=20.160, p<.001).

Conclusions:
Greater depressive symptoms in HF FCGs were predicted by worse sleep, greater burden, worse family functioning, and white race. Caregiver demand/strain had less effect on depressive symptoms in the XL/L allele group whereas these factors affected the any S-type group. Allele variants of the 5-HTTLPR may interact with caregiving burden to affect depressive symptoms differentially and may help identify caregivers at greater risk for depressive symptoms. Improving sleep and reducing caregiving demand may be important targets for intervention.
Abstract 12708: Adherence to Healthy Lifestyle and Cardiovascular Diseases in Chinese
Authors: Qi Lu , Lv Jun , Yu Canqing , Guo Yu , Bian Zheng , Yang Ling , Chen Yiping , Tang Xuefeng , Zhang Weiyuan , Qian Yijian , Huang Yuelong , Wang Xiaoping , Chen Junshi , Chen Zhengming , Li Liming
Published: April 2024

Introduction:
Adherence to a combination of healthy lifestyle factors has been related to a considerable reduction of cardiovascular risk in white populations; however, little is known whether such associations persist in non-white populations.

Methods:
We examined the associations of six lifestyle factors with ischemic heart disease and ischemic stroke (IS) in the China Kadoorie Biobank of 461,211 participants aged 30-79 years without cardiovascular diseases, cancer, or diabetes at baseline. Low-risk lifestyle factors were defined as non-smoking or having stopped for reasons other than illness, alcohol consumption of <30 g/day, median or higher level of physical activity, diet rich in vegetables and fruits and low in red meat, body mass index of 18.5-23.9 kg/m
2
, and waist-to-hip ratio <0.90 for men and <0.85 for women.

Results:
During a median of 7.2 years of follow-up, we documented 3,331 incident major coronary events (MCE) and 19,348 incident IS. In multivariable-adjusted analyses, current non-smoking, light-to-moderate alcohol, high physical activity, diet rich in vegetables and fruits and low in red meat, and low adiposity were independently associated with reduced risks of MCE and IS. Compared with participants without any low-risk factors, the hazard ratio (95% confidence interval) for those with ≥5 low-risk factors was 0.37 (0.16, 0.84) for MCE and 0.50 (0.40, 0.64) for IS. Approximately 60.8% (33.4%, 78.8%) of the MCE and 29.3% (17.6%, 40.1%) of the IS were attributable to poor adherence to healthy lifestyle.

Conclusions:
Our data indicate that adherence to healthy lifestyle may substantially lower the burden of cardiovascular diseases in Chinese.
Abstract 12766: Cardiac Sympathetic Nerve System Activity Evaluated by Cardiac I-123 Metaiodobenzylguanidine Scintigraphy in Heart Failure Patients With Preserved or Reduced Ejection Fraction
Authors: Goto Toshihiko , Wakami Kazuaki , Mori Kento , Banno Tomoyuki , Kikuchi Shohei , Sugiura Tomonori , Fujita Hiroshi , Fukuta Hidekatsu , Ohte Nobuyuki
Published: April 2024

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is the predominant form of heart failure. However, there is no proven therapy for HFpEF. In contrast, significant benefits of beta-blockers that inhibit cardiac nerve system activity have been established in patients with heart failure with reduced ejection fraction (HFrEF). The purpose of this study is to compare cardiac sympathetic nerve system activity in patients with HFpEF versus HFrEF.

Methods:
The I-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed to evaluate cardiac sympathetic nerve system activity in 48 heart failure patients (age 77.0±10.6 years; male 52.1%). We compared the early and delayed heart/mediastinum (H/M) ratio and the washout rate (WR) in patients with HFpEF (left ventricular ejection fraction; LVEF≥50%, n=20) and HFrEF (LVEF<50%, n=28).

Results:
There were no differences in age and sex between two groups. LVEF was significantly higher in patients with HFpEF than in those with HFrEF (62.5±11.7 vs 31.7±9.1%, p<0.001). Plasma BNP level was significantly lower in patients with HFpEF than in those with HFrEF (205.1 [IQR, 155.0-430.5] vs 369.0 [IQR, 196.6-662.1] pg/mL, p=0.04). Plasma norepinephrine level was not different between HFpEF patients and HFrEF patients (428.5 [IQR, 210.5-676.3] vs 392.5 [IQR, 307.2-535.8] pg/mL, p=0.93). No significant differences were found in the early H/M ratio (2.17±0.46 vs 2.10±0.32, p=0.53) and in the delayed H/M ratio (1.94±0.53 vs 1.80±0.35, p=0.91) between HFpEF patients and HFrEF patients. The WR was also similar in HFpEF patients and HFrEF patients (37.9±17.0 vs 46.3±16.4%, p=0.09). The use of beta-blockers was significantly lower in patients with HFpEF than in those with HFrEF (35.0 vs 71.4%, p=0.01).

Conclusions:
Although the use of beta-blockers was lower in patients with HFpEF as compared to in those with HFrEF, cardiac sympathetic nerve system activity was elevated to a similar extent between patients with HFpEF and HFrEF. These findings suggest that cardiac sympathetic nerve system is a promising therapeutic target in patients with HFpEF.
Abstract 12861: Assessment of Both Coronary Microvascular Damage and Epicardial Flow Velocity Measurement Immediately After Successful Percutaneous Coronary Intervention Predicts In-Hospital Complications and Survival in ST-Segment Elevation Myocardial Infarction
Authors: Yamamuro Atsushi , Tamita Koichi , Yoshikawa Junichi , Shuichiro Kaji , Furukawa Yutaka
Published: April 2024

Background:
Quantitative measurement of post-reperfusion epicardial flow velocity by a Doppler guidewire can predict clinical cardiac events in ST-segment elevation myocardial infarction (STEMI). It has also been reported that the coronary flow velocity pattern in patients with microvascular obstruction is characterized by the presence of early systolic retrograde flow and a rapid diastolic deceleration time (DDT). The purpose of this study was to examine the role of assessing both epicardial flow velocity and microvascular damage in the prediction of in-hospital complications and survival after percutaneous coronary intervention (PCI).

Methods:
Two hundred and fifty-one consecutive patients with first anterior STEMI who underwent successful PCI were subjected to coronary flow measurement with a Doppler guidewire. The coronary flow velocity spectrum provided the following parameters: time-averaged peak velocity (cm/s, APV), systolic peak velocity (cm/s) and DDT (ms). We defined the presence of microvascular obstruction as DDT ≤600 ms and the presence of systolic flow reversal, and slow epicardial flow as resting APV ≤10cm/s. We classified the patients into three categories: without microvascular obstruction (group 1, n=140), with microvascular obstruction and normal epicardial flow (group 2, n= 51, with microvascular obstruction and slow epicardial flow (group 3, n=60). The clinical event rate was compared among the 3 groups.

Results:
The in-hospital event rates for congestive heart failure (15/140 [11%], 15/51 [29%] and 34/60 [57%], respectively;
P
< 0.01), left ventricular thrombus (3/140 [2%], 9/51 [18%] and 14/60 [23%], respectively;
P
< 0.01), and cardiac rupture (0/140 [0%], 5/51 [10%], and 16/60 [27%];
P
< 0.01) were highest in group 3 and lowest in group 1. Group 3 was at the highest risk of cardiac death, while group 1 was at the lowest (0/140 [0%], 3/51 [6%], and 12/60 [20%];
P
< 0.01).

Conclusions:
Assessment of both coronary microvascular damage and epicardial flow velocity can accurately predict in-hospital complications and survival in STEMI patients who underwent successful reperfusion of the infarct-related coronary artery, identifying a subset of high risk patients.
Abstract 12874: E/e’ SV is a Better Predictor of Outcome Than E/e’ in Patients With Heart Failure With Preserved Left Ventricular Ejection Fraction
Authors: Kanda Takashi , Fujita Masashi , Iida Osamu , Masuda Masaharu , Okamoto Shin , Ishihara Takayuki , Nanto Kiyonori , Sunaga Akihiro , Tsujimura Takuya , Okuno Shota , Matsuda Yasuhiro , Yanaka Koji , Ohashi Takuya , Kawai Hiroyuki , Tsuji Aki , Hata Yosuke , Uematsu Masaaki
Published: April 2024

Introduction:
Predictors of outcome in patients with heart failure with preserved left ventricular ejection fraction (HFpEF) remain unclear. The ratio of early diastolic transmitral flow velocity to early diastolic myocardial velocity (E/e’) has been proposed as one of them, but the predictive accuracy remains insufficient.

Hypothesis:
We hypothesized E/e’ SV, E/e’ normalized by the stroke volume (SV), may be a better predictor of outcome in patients with HFpEF than E/e’, by reflecting the terminal slope of the end-diastolic pressure-volume relation, i.e., stiffness of the left ventricle. The aims of this study were to propose a novel echocardiographic index, E/e’ SV, and investigate the feasibility and accuracy of this method in HFpEF patients.

Methods:
Echocardiography including E/e’ SV measurement was performed in consecutive 43 patients with HFpEF at discharge in index hospitalization (female 22 patients (51%), age 78±9 years old). Patients were followed for a median of 6.5 months. The end points included the admission for heart failure and cardiovascular death.

Results:
During the follow-up, 9 patients (21%) encountered the end points. In ROC analysis, E/e’ SV was a better predictive factor than E/e’ (E/e’ SV: AUC=0.820; E/e’: AUC=0.768). Kaplan-Meier analysis showed patients with E/e’ SV>0.420 had a poorer prognosis than those with E/e’ SV<0.420 (P<0.01). In Cox regression multivariate analysis, high E/e’ SV was an independent predictor of event-free survival (Adjusted Hazard ratio [95% CI] = 17.2 [3.1, 94.8] (p=0.001)).

Conclusion:
E/e’ SV is a better predictor of outcome in patients with HFpEF than E/e’.
Abstract 12886: In-hospital and Early Post-discharge Troponin Elevations Among Patients Hospitalized for Heart Failure: Insights From the ASTRONAUT Trial
Authors: Greene Stephen J , Zannad Faiez , Fonarow Gregg C , Subacius Haris , Triggiani Marco , Ambrosy Andrew P , Böhm Michael , Butler Javed , Chioncel Ovidiu , Maggioni Aldo P , Solomon Scott D , Vaduganathan Muthiah , Gheorghiade Mihai , Senni Michele
Published: April 2024

Introduction:
Troponin level is commonly elevated among patients hospitalized for heart failure (HF) and may correlate with worse clinical outcomes. The prognostic significance of early post-discharge troponin level and persistent troponin elevation is unclear.

Methods:
The ASTRONAUT trial randomized 1,615 hospitalized HF patients with ejection fraction ≤40% to daily aliskiren or placebo, in addition to standard care. Troponin I was measured per protocol at baseline and 1-month in a core lab with elevated level defined as >0.04 ng/mL. Outcomes were compared by presence/ absence of troponin I elevation at baseline and 1-month. Landmark analysis was performed to account only for events subsequent to troponin measurement.

Results:
Overall, 1,469 (91.0%) patients had troponin data at baseline, of which 609 (41.5%) had elevated levels (median 0.10 ng/mL). At 1 month, 1,301 (80.6%) patients had troponin data, of which 389 (29.9%) had elevated levels (median 0.10 ng/mL). Among patients with baseline elevated troponin with troponin data at 1 month, 313/518 (60.4%) had persistently elevated troponin level. After adjustment, elevated baseline troponin was not significantly associated with 1-year all-cause death or cardiovascular mortality/ HF hospitalization
(Table).
However, 1-month troponin elevation was independently predictive of 1-year clinical outcomes. The association between 1-month troponin elevation and outcomes was not influenced by presence/ absence of baseline troponin elevation (P for interaction ≥ 0.69).

Conclusion:
Troponin I was elevated in >40% of hospitalized HF patients, and remained persistently elevated in >60% of these patients early post-discharge. Elevated troponin I levels at 1-month follow-up, but not during hospitalization, were independently predictive of increased clinical events. Measurement of troponin I during the early post-discharge vulnerable phase should be considered as a practical means of risk stratification.
Abstract 12889: Drug-Eluting Stents in the Treatment of Saphenous Vein Graft Disease: Disappointing Outcome During Long-term Follow-up
Authors: Ruggiero Nicholas J , Fischman David L , Durney Philip , Madsen Brandon M , Walinsky Paul , Gannon Michael , Jasti Babu , Ogilby David , McCarey Melissa , Adams Suzanne , Savage Michael P
Published: April 2024

Introduction:
Drug-eluting stents (DES) have been shown to have superior short term outcomes in the treatment of saphenous vein graft (SVG) disease compared to bare metal stents.

Hypothesis:
The goal of this study was to assess the long term clinical outcome of all patients with SVG disease treated with DES.

Methods:
183 consecutive patients undergoing SVG intervention with DES were evaluated. Post-procedure, antiplatelet therapy included aspirin indefinitely and dual antiplatelet therapy for a minimum of 1 year. Major adverse cardiac events (MACE) were assessed at a mean follow-up of 5 years. MACE was defined as any of the following: death, stroke, myocardial infarction, repeat bypass surgery, repeat target vessel revascularization, or stent thrombosis.

Results:
The study population consisted of 149 men and 34 women with a mean age of 69 ± 10 years. Diabetes was present in 83 (45%) and acute coronary syndromes were present in 116 (63%). Mean SVG age was 12 ± 6 years. Diffuse disease (≥ 30 mm of treated disease and/or 3 or more lesions in a single vessel) was present in 37%. A total of 243 lesions were treated with 395 DES. Procedural techniques during DES deployment included direct stenting in 50%, pretreatment with intracoronary nicardipine in 49%, and use of a distal protection device in 38%. Kaplan Meier analysis of long-term MACE free survival is shown in the Figure. Although only 18% of patients had a MACE at one year, continued events were common after the first year. At 49 months, 50% of the patients had one or more MACE. Event free survival which was 82% at 1 year was only 41% at 5 years. MACE free survival after first and second generation DES were similar.

Conclusions:
The long-term outcome after percutaneous intervention of aortocoronary bypass vein grafts continues to present a clinical challenge. Within 5 years after DES placement for SVG disease, fewer than half of the patients remain event free.
Abstract 12897: The Synergistic Effects of Fatigue and Depression on Use of Medical Services in Patients With Heart Failure
Authors: Heo Seongkum , McSweeney Jean , Tsai Pao-Feng , Ounpraseuth Songthip
Published: April 2024

Introduction:
Heart failure (HF) is an expensive clinical condition, which imparts a considerable burden on patients and society. Fatigue and depression are the most common physical and psychological symptoms, and together may have more impact on use of medical services than one symptom alone.

Hypothesis:
We hypothesized that fatigue and depression would have the synergistic effects on use of different medical services controlling for common covariates.

Methods:
We conducted a secondary data analysis of a university medical center electronic database (N = 582, mean age 63 ± 14 years, 54% males). Data were collected on fatigue, depression, covariates (i.e., sociodemographic and clinical characteristics, vital signs, laboratory tests [serum troponin, albumin, triglycerides, creatinine, sodium, hemoglobin, monocytes, and neutrophils], and medication [beta-blockers, antidepressants, and angiotensin converting enzyme inhibitors]), and frequency of medical service use based on CPT codes. Patients were categorized into one of four symptom groups based on ICD-9 codes: no symptom, fatigue only, depression only, and fatigue and depression. General linear regression was used to analyze the data.

Results:
The mean number of total medical service use was 96.5 ± 84.3 over 3 years. The mean number in the fatigue and depression group (152.6 ± 103.4) was greater than the fatigue only (122.9 ± 97.9, p = .016), depression only (84.3 ± 62.0, p < .001), and no symptom groups (61.7 ± 46.7, p < .001) controlling for covariates. In further analyses, the numbers of medical service use in the fatigue and depression group compared with the other groups were greater in evaluation and management services (e.g., inpatient and outpatient services, p < .001), radiology services (e.g., diagnostic imaging and ultrasound, p < .001), and medicine services (e.g., medical services and procedures such as cardiovascular, p < .05).

Conclusion:
Fatigue and depression showed synergistic impact on the number of total medical service use. Clinicians should assess and manage fatigue and depression together and provide interventions to manage them effectively to assist in reducing medical service use.
Abstract 12919: Co-aligned and Inherently Co-registered Intravascular Ultrasound and Optical Coherence Tomography in a Hybrid Imaging Catheter is Feasible for Characterizing Coronary Artery Disease
Authors: Li Brian H , Harduar Mark , Virdi Kuljit , Toma Jonathan , Alves Natasha , Courtney Brian K
Published: April 2024

Introduction:
Combined use of intravascular ultrasound (IVUS) and optical coherence tomography (OCT) demonstrates synergistic benefits, which may improve the characterization and therapeutics of coronary artery disease. However, sequential use of stand-alone catheters is impractical.

Hypothesis:
IVUS and OCT can be implemented in a dual-modality catheter with co-alignment of imaging beams, allowing simultaneous imaging of coronary lesions that are inherently co-registered.

Methods:
A 3-French rotational custom hybrid IVUS-OCT imaging catheter was built using a 40 MHz ultrasound transducer with embedded OCT imaging fiber optics, as well as co-alignment of the IVUS and OCT imaging centers. Ex-vivo intraluminal IVUS and OCT images of 70 coronary artery segments from 5 cadaveric autopsies were acquired simultaneously at 25 frames/sec with 5 mm/sec pull back. Imaging at 100 frames/sec was also briefly conducted. Thirty segments had potential pathological findings and underwent histologic slicing and hematoxylin-eosin staining at 250μm intervals. Morphological features were identified based on standard criteria for IVUS and OCT, then compared to corresponding histology findings.

Results:
IVUS and OCT were well co-registered based on fiduciary markings. A number of vascular pathologies were identified, including normal, fibrous, lipid-rich, calcified, and thrombus tissues. These findings were confirmed on corresponding histology. Complementary features of IVUS and OCT were also qualitatively apparent. IVUS showed deeper image depth to allow assessment of plaque size and vascular remodeling. OCT showed superior near field imaging, resolution and tissue contrast.

Conclusions:
We demonstrated feasibility of co-aligning IVUS and OCT, providing co-registered hybrid images that highlight the complementary advantages of both modalities. Quantitative comparison and validation of this technology is on-going.
Abstract 12936: Hepatic Steatosis and Cardiometabolic Risk in Rural India: A Prospective Cohort Study
Authors: Spahillari Aferdita , Barik Anamitra , Shah Ravi V , Murthy Venkatesh L , Das Ranendra , Rai Rajesh K , Das Kaushik , Santra Amal , Hembram Jaba Ranjan , Bhattacharya Dilip , Das Saumya , Chowdhury Abhijit
Published: April 2024

Background:
While liver fat is linked to metabolic disease in first-world environments, its prevalence and impact in rural locations are less clear. We aimed to measure the association between liver fat, cardiometabolic profiles and subclinical cardiovascular disease (CVD) in a large rural Indian cohort.

Hypothesis:
We hypothesized that despite lower BMI, the presence of liver fat would be related to cardiometabolic risk and subclinical CVD.

Methods:
In 4691 individuals in the Birbhum Population Project (BPP) in West Bengal, India, we performed liver ultrasonography, carotid ultrasound and biochemical and clinical profiling. We assessed the association of liver fat with risk factors (dysglycemia, dyslipidemia, hypertension) and subclinical CVD (by carotid intimal-medial thickness) in models adjusted for age, sex, income, education, BMI, waist circumference, smoking, blood pressure and glucose.

Results:
Rural Indians exhibited a higher visceral adiposity index and pro-atherogenic dyslipidemia at a lower BMI than Americans. Individuals with any degree of liver fat by ultrasound had a greater probability of dysglycemia (adjusted odds ratio OR=1.67, 95%CI 1.31-2.12, P<0.0001) and pro-atherogenic dyslipidemia (OR=1.33, 95% CI 1.07-1.63, P=0.009), but not hypertension. We observed a positive association between liver fat and carotid intimal-medial thickness (CIMT) in an unadjusted model (β=0.02, P=0.0001), which was extinguished after adjustment for cardiometabolic risk factors.

Conclusion:
In a large population of rural Indians, presence of liver fat was associated with prevalent cardiometabolic risk and subclinical CVD at lower BMIs relative to multi-ethnic Americans, though the association with subclinical CVD was extinguished after adjustment. These results underscore the emerging relevance of hepatic steatosis in the developing world, and suggest efforts to target this accessible phenotype for cardiometabolic risk prevention.
Abstract 12937: The Risk for Major Bleeding Was Similar in Patients Receiving Ticagrelor or Aspirin After TIA or Acute Ischemic Stroke in the SOCRATES Study
Authors: Easton J D , Albers Gregory W , Aunes Maria , Amarenco Pierre , Denison Hans , Evans Scott R , Held Peter , Jahreskog Marianne , Johnston S C , Jonasson Jenny , Minematsu Kazuo , Molina Carlos A , Wang Yongjun , Wong Lawrence K ,   for the SOCRATES Steering Committee and Investigators
Published: April 2024

Introduction:
The randomized, double-blind SOCRATES study (NCT01994720) was the first trial with the reversibly binding P2Y12 receptor blocker ticagrelor in patients with acute ischemic stroke (AIS) or TIA. The main safety objective was assessment of PLATO defined major bleedings, with special focus on intracranial hemorrhage (ICH).

Methods:
An independent adjudication committee blinded to study treatment (ticagrelor or ASA) classified bleedings according to PLATO, TIMI and GUSTO definitions. The definition of major bleeding was adapted to the acute stroke population by excluding asymptomatic hemorrhagic transformations of ischemic cerebral infarctions and micro-bleeds <10 mm evident only on gradient-echo MRI from being considered ICH and major bleedings. The on-treatment (OT) period was defined as OT + 7 days after stop of study drug.

Results:
In total, 13130 (of 13199 randomized) patients received at least one dose of study drug (safety analysis set). PLATO major bleedings occurred in 31 (0.5%) patients on ticagrelor and 38 (0.6%) on ASA (HR 0.83, 95% CI 0.52 to 1.34). TIMI major bleedings were identified in 21 patients on ticagrelor vs 27 on ASA; and for GUSTO severe 18 vs 21. Patients with PLATO major bleedings had a mean age of 70.2 ±11.2 years, 60.9% were men, and 78.3% were randomized as AIS and 21.7% as TIA, as compared with the overall SOCRATES safety population with mean age 65.9 ± 11.3 years, 58.5% men, AIS in 73.3% and high-risk TIA in 26.7%. The most common locations of major bleedings were intracranial and gastrointestinal. ICH was reported in 12 (0.2%) patients on ticagrelor and 18 (0.3%) on ASA. There were 6 spontaneous, 3 traumatic and 3 procedural ICHs on ticagrelor. For ASA the corresponding numbers were 13, 3 and 2. Thirteen (4 on ticagrelor vs 9 on ASA) were hemorrhagic strokes and 4 (2 vs 2) were symptomatic hemorrhagic transformations. The ICH was fatal in 6/12 patients on ticagrelor and 4/18 on ASA. In total, 9 fatal bleedings occurred on ticagrelor and 4 on ASA. The composite of ICH or fatal bleeding included 15 patients on ticagrelor versus 18 on ASA.

Conclusions:
Antiplatelet therapy with ticagrelor in patients with AIS or TIA showed a similar bleeding profile as ASA for major bleedings. There were few ICHs.
Abstract 12939:
18
F-Sodium Fluoride Positron Emission Tomography for Molecular Imaging of Coronary Atherosclerosis Based on Computed Tomography Analysis
Authors: Kitagawa Toshiro , Yamamoto Hideya , Toshimitsu Shinya , Sasaki Ko , Senoo Atsuhiro , Hirokawa Yutaka , Kihara Yasuki
Published: April 2024

Background:
Arterial
18
F-sodium fluoride (
18
F-NaF) uptake on positron emission tomography (PET) has been reported to reflect active atherosclerosis with osteogenesis and inflammatory stimulus. We evaluated the relation of
18
F-NaF uptake to computed tomography (CT)-based coronary atherosclerosis.

Methods:
We enrolled 25 patients with ≥1 coronary atherosclerotic lesions detected on cardiac CT, who underwent
18
F-NaF PET/CT. Each lesion was evaluated with luminal stenosis and plaque types (calcium plaque = CP, non-calcified plaque = NCP, and partially calcified plaque = PCP) on coronary CT angiography. For CP and PCP, focal calcium density and volume were measured on plain CT images. For NCP and PCP, the presence of CT-based high-risk features (minimum CT density ≤30 Hounsfield units, and vascular remodeling index ≥1.1) was determined. Focal
18
F-NaF uptake of each lesion on PET/CT was quantified by maximum tissue-to-background ratio (TBR
max
).

Results:
A total of 87 lesions were studied. In a patient-based analysis, 12 patients having a past history of myocardial infarction or unstable angina showed higher maximum TBR
max
per patient than those without (Fig 1). In a lesion-based analysis, PCP had higher TBR
max
than CP and NCP, and the lesions with high-risk features had higher TBR
max
than those without (Fig 2, 3), while TBR
max
did not correlate with focal calcium density (r = 0.05, p = 0.65) or volume (r = 0.18, p = 0.12). On multivariate analysis adjusted for the presence of >50% stenosis, focal calcium density and volume, and location of lesions, the plaque type of PCP showed a significant correlation with increased TBR
max
(β = 0.57, p < 0.0001).

Conclusions:
Coronary arterial
18
F-NaF uptake, independently of calcium amount, is related to the heterogeneous and high-risk features of coronary atherosclerosis based on CT analysis.
18
F-NaF PET/CT may provide a new molecular imaging approach to identify high-risk patients and coronary lesions, in combination with cardiac CT.
Abstract 12940: Prognosis of Hemodialysis Patients With Severe Aortic Stenosis: Findings From the Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis (CURRENT AS) Registry
Authors: Kawase Yuichi , Kadota Kazushige , Taniguchi Tomohiko , Morimoto Takeshi , Iwasaki Keiichiro , Kuwayama Akimune , Miura Katsuya , Ohya Masanobu , Shimada Takenobu , Amano Hidewo , Fuku Yasushi , Maruo Takeshi , Kimura Takeshi
Published: April 2024

Background:
Prognosis of hemodialysis (HD) patients with severe aortic stenosis (AS) remains unclear.

Methods and Results:
The CURRENT AS registry, a Japanese multicenter registry enrolled 3815 consecutive patients with severe AS. There were 1197 patients treated with the initial aortic valve replacement (AVR) strategy including surgical AVR and transcatheter aortic valve implantation and 2617 patients treated with the conservative strategy. The median follow-up duration after the index echocardiography was 1361 days, with a 90% follow-up at 2-year. HD patients accounted for 11% (405/3815 patients). The cumulative 5-year incidence of all-cause death (primary outcome measure) was significantly higher in HD patients than in non-HD patients in both the entire cohort and the initial AVR group (see Figure). Among HD patients, the initial AVR group as compared with the conservative group was associated with significantly lower cumulative 5-year incedences of all-cause death (see Figure) and sudden death (10.2% versus 31.7%, P<0.001). Operative mortality rate at 30-day after AVR in HD patients was as high as 7.7% (10/131 patients).

Conclusions:
Being on HD indicates a grimmer prognosis in patients with severe AS, even when treated with the initial AVR strategy. The initial AVR strategy in HD patients was associated with high operative mortality risk, while it was associated with lower risk of death in long-term.