bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16346: Soluble P-Selectin Predicts Lower Extremity Peripheral Artery Disease Incidence and Change in the Ankle Brachial Index: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Wassel Christina L , Berardi Cecilia , Pankow James S , Larson Nicholas B , Decker Paul A , Hanson Naomi Q , Tsai Michael Y , Criqui Michael H , Allison Matthew A , Bielinski Suzette J
Published: July 2021

Background:
Given the global burden of peripheral arterial disease (PAD) and the associated morbidity, continuing investigation of potential biomarkers as therapeutic targets for preventing PAD is warranted. The association of P-selectin, an endothelial cell adhesion molecule, with the ankle brachial index (ABI) and PAD is not well established. Thus, we examined the association of circulating P-selectin with prevalent and incident PAD, the ABI, and change in the ABI.

Methods:
The Multi-Ethnic Study of Atherosclerosis (MESA) is a prospective population-based cohort including 6814 non-Hispanic white, African American, Hispanic and Chinese men and women aged 45-84 at baseline (2000-02). For this analysis, 5700 participants with both P-selectin at Exam 2 (2002-04) and the ABI at Exam 3 (2004-05) were available, with change in ABI from Exam 3 to Exam 5 (2010-12) available on 4276 participants. P-selectin was modeled per standard deviation (SD), while prevalent and incident PAD were defined as ABI ≤ 0.90 after excluding those with ABI>1.4. Linear regression was used for ABI, growth curve models for change in ABI, and logistic regression for prevalent and incident PAD.

Results:
In models adjusted for demographics, lifestyle factors, comorbidities, blood pressure, lipids, fasting glucose, c-reactive protein (CRP), interleukin-6 (IL-6), D-dimer, and fibrinogen, each SD (13 ng/mL) higher P-selectin was significantly associated with 0.007 lower ABI (95% CI ((-0.011, -0.004)), p<0.001), and an average change in the ABI of -0.006 ((-0.010, -0.003, p<0.001). P-selectin was also significantly associated with a 1.14-fold greater odds of prevalent PAD ((1.00, 1.28), p=0.04), and a 1.30-fold greater odds of incident PAD ((1.10, 1.55), p<0.001). There were no significant interactions of p-selectin by race/ethnicity or gender. Addition of P-selectin to models containing traditional PAD risk factors as well as CRP, IL-6, D-dimer and fibrinogen did not improve the c-statistic or net reclassification for incident PAD.

Conclusions:
P-selectin appears to be strongly associated with the development of PAD. However, further research is needed in population-based studies to confirm prospective associations of p-selectin with incident PAD and change in the ABI.
Abstract 16388: Residual SYNTAX Score and Survival Following Coronary Artery Bypass Grafting: Analysis of 1608 Patients
Authors: Melina Giovanni , Angeloni Emiliano , Refice Simone , Benegiamo Cristian V , Lechiancole Andrea , Roscitano Antonino , Bianchini Roberto , Spitaleri Pierpaolo , Capuano Fabio , Comito Cosimo , Goracci Massimo , Rosato Stefano , Seccareccia Fulvia , Monti Francesco , Serdoz Roberto , Colivicchi Furio , Paneni Francesco , Sinatra Riccardo
Published: July 2021

Introduction:
We and others have previously shown that SYNTAX score predicts outcome in patients undergoing coronary artery bypass grafting (CABG). More recently, the residual SYNTAX score (rSS) has emerged as a reliable tool to quantify the extent and complexity of untreated coronary lesions after percutaneous coronary intervention (PCI). Indeed, rSS is an independent predictor of morbidity and mortality following PCI. Whether rSS may help to stratify mortality risk after CABG remains largely unknown.

Hypothesis:
The present study was designed to investigate the predictive value of rSS on mortality risk in a prospective cohort of patients undergoing surgical revascularization.

Methods:
Average baseline SYNTAX score calculated on 1608 patients (mean age 68±6 years, F:M 213:1395) undergoing isolated first-time CABG was 26.6 ± 9.4. The rSS measured after CABG was 3.2 ± 1.8 (p<0.001 vs baseline). Complete revascularization was assumed as rSS=0. Based on rSS tertiles, the study population was stratified in low rSS (0<rSS<2), intermediate rSS (2<rSS<8) and high rSS (rSS>8).

Results:
Following CABG, 1157/1608 (71.9%) patients had rSS=0, whereas 209/1608 (12.9%) had low rSS, 176/1608 (10.9%) had intermediate rSS and 66/1608 (4.1%) had high rSS. At Kaplan-Meier analysis of survival subjects in the highest rSS tertile (rSS>8) showed significant worse survival as compared to patients with rSS=0, 0<rSS<2 and 2<rSS<8 (χ
2
77.1, p<0.0001). Cox proportional-hazards regression analysis adjusted for age, gender, diabetes, preoperative LV and renal function showed rSS to be an independent predictor of 1-year survival (b 0.48, p<0.0001).

Conclusions:
These unanticipated findings suggest that residual SYNTAX score may stratify mortality risk in patients undergoing isolated first-time CABG. Our study may set the stage for further investigation addressing this important clinical question.
Abstract 16393: Right Ventricular Energetics and Power in Pulmonary Regurgitation vs. Stenosis Using Four-Dimensional Phase-Contrast Magnetic Resonance
Authors: Kutty Shelby , Fernandes Joao Filipe , Konecny Filipe , Xiao Yunbin , Lof John , Kuehne Titus , Hammel James
Published: July 2021

Background:
We investigated kinetic energy (KE) and power efficiency in porcine models of pressure and volume loaded right ventricle (RV) using four-dimensional phase-contrast magnetic resonance imaging (4DPC-MRI).

Methods:
4DPC-MRI was performed in pig models of pulmonary stenosis (PS) and pulmonary regurgitation (PR) at baseline and at 10-12 weeks of creation of the model, in conjunction with cardiac catheterization. Phase-contrast velocities were computed over 1 cardiac cycle (25 time-steps, MevisFlow and CAIPI, Fraunhofer MEVIS, Germany), with segmentation of a moving left ventricle mask based on cine images. The segmented mask was applied to the respective calculated 3D velocity vector field per time-step. Mean KE and KE curve profiles were measured, normalized for RV volumes and compared between PS and PR groups. Catheterization pressures and pressure-volume loops (Transonic Scisense Inc.) were used to calculate RV stroke work (RVSW) and stroke power. RV power efficiency was calculated as the ratio between RV power output and stroke power.

Results:
Eight pigs (4 PS and 4 PR) were studied. Table shows demographics, volumetry, KE and power data compared between groups. Both groups had similar KE pre-procedure but significant changes in KE post-procedure. In addition, the PR group had higher RV power efficiency and KE (87.1%±14.3%; 23.5±5.3, respectively) than PS group (21.4%±15.7%; 10.9±3.9) post-procedure.

Conclusions:
Volume loaded RV from PR had higher KE and power efficiency compared to pressure load from PS. These parameters represent the KE of blood in the RV and the net energy transferred into the pulmonary artery over one cardiac cycle. PS and PR groups have different RV work load, and they operate at different energy levels.
Abstract 16397: Correlates of Successfully Achieving Statin Therapy Targets in Pediatric Patients
Authors: Mendelson Michael , Regh Todd , Harker Heather , Palumbo Nicole , Nevin James , Johnson Phillip K , Griggs Suzanne , Boghani Meera , Desai Nirav , Yellen Elizabeth , Buckley Lucy , Baker Annette , Gillman Mathew , Zachariah Justin , Graham Dionne , de Ferranti Sarah D
Published: July 2021

Introduction:
Targeting LDL-C goals for statin therapy is currently recommended for children and adolescents in NHLBI pediatric guidelines; however, there is limited information about clinical factors, especially modifiable ones, that impact successful achievement of LDL-C goals.

Methods:
We analyzed data prospectively collected as part of a quality improvement initiative, SCAMP® (Standardized Clinical Assessment and Management Program), in the Preventive Cardiology Clinic at Boston Children’s Hospital, Boston, MA. We included patients initiated on statin therapy from September 2010 to March 2014. Achieving LDL target was defined as an LDL-C < 130 mg/dL or an LDL-C < 100mg/dL with a high level risk factor (i.e. diabetes, etc.). The impact of baseline CVD risk factors were assessed in Cox proportional hazards models.

Results:
Among the 1521 pediatric patients and 3813 clinical encounters that occurred over the 3.5 year period, 116 patients were defined as initiating statin therapy. Complete data was available on 79 patients (mean [SD] age 14 [4] years; 47% female; median [IQR] LDL-C 215 [79] mg/dL). The probability of achieving LDL-C goal within 365 and 500 days of starting a statin was 0.55 (95% CI 0.44-0.68) and 0.67 (0.55-0.79), respectively; Figure 1. In univariate analyses, female sex (p=0.01) and lower baseline LDL-C (p=0.04) was associated with more rapid achievement of LDL-C goals, but not age (p=0.8), BMI (p=0.2), exercise (p=0.6), nutritional factors (p=0.3), screen time (p=0.3), cigarette smoking (p=0.9), or family history of early CVD (p=0.3).

Conclusions:
The majority of children reached LDL-C treatment goals with statin therapy. Baseline modifiable lifestyle CVD risk factors such as diet and exercise were not associated with achieving LDL-C goal on statin therapy in children and adolescents. Increased support and monitoring may be needed, particularly for males, in order to achieve therapy goals.
Abstract 16404: CETP Inhibitor K-312 Lowers PCSK9 Expression and LDL Cholesterol Levels in vivo
Authors: Miyosawa Katsutoshi , Singh Sasha , Watanabe Yuichiro , Shibata Haruki , Mizuno Ken , Tanabe Sohei , Aikawa Masanori
Published: July 2021

Background:
Despite potent LDL-cholesterol (LDL-C) therapies, substantial residual cardiovascular risk remains. Proprotein convertase subtilisin/kexin 9 (PCSK9) is a promising target for lowering LDL-C. We recently demonstrated that K-312, originally found as a cholesteryl ester transfer protein (CETP) inhibitor, decreased PCSK9 expression in vitro through the reduction of its promoter activity. The present study has further examined the underlying molecular mechanisms and in vivo effects of K-312 on PCSK9 levels using mass spectrometry.

Methods and Results:
CETP silencing by siRNA in the human hepatocyte cell line HepG2 did not compromise suppression of PCSK9 expression by K-312, indicating a mechanism independent of CETP inhibition. Transcription factors sterol-regulatory element binding protein (SREBP)-1 and SREBP-2 bind to the sterol regulatory element (SRE) of PCSK9 promoter when their precursor forms are cleaved into active forms. K-312 treatment decreased binding of SREBP-1 and SREBP-2 to SRE of the PCSK9 promoter (chromatin immunoprecipitation) and active forms of SREBP-1 and SREBP-2 (western blotting), suggesting the suppression of PCSK9 expression by K-312 involves SREBP-1 and SREBP-2. We then examined the effects of K-312 in cholesterol-fed New Zealand White rabbits administered either vehicle (N=7) or K-312 30 mg/kg (N=7) for 2 weeks. K-312 treatment decreased LDL-C (vehicle: 272.5 ± 42.2 mg/dl; K-312: 193.0 ± 36.5 mg/dl), increased HDL cholesterol (vehicle: 29.9 ± 3.7 mg/dl; K-312: 93.3 ± 14.7 mg/dl) and decreased PCSK9 mRNA levels in the liver by 63%. We further used two mass spectrometry-based approaches to measure PCSK9 levels in rabbit plasma: spectral counting and a novel high resolution (HR)-MS/MS quantification method. Immunoprecipitation of PCSK9 successfully enriched PCSK9 signal. Spectral counting and HR-MS/MS of PCSK9 peptides both demonstrated that K-312 treatment significantly decreased plasma PCSK9 levels by 76% (p<0.01) and 60% (p<0.05), respectively.

Conclusion:
K-312 may lower LDL cholesterol levels by suppressing CETP activity and PCSK9 expression, serving as a novel therapy for dyslipidemia and cardiovascular disease.
Abstract 16411: Abo Blood Group and Risk of Myocardial Infarction in Hispanics
Authors: Huang Tao , Li Yanping , Xu Min , Baylin Ana , Campos Hannia , Qi Lu
Published: July 2021

Hypothesis:
ABO blood group has been associated with myocardial infarction (MI) in Caucasians. This study evaluated whether genotype-derived ABO blood group associated with MI in Hispanics, and whether lifestyle risk factors modified the associations.

Methods:
Cases (n=2273) with a first acute nonfatal MI and population-based controls (n=2274) living in Costa Rica were studied. Five ABO single-nucleotide polymorphisms (SNPs) were genotyped.

RESULTS:
Three SNPs (rs687289, rs507666, and rs579459) at ABO locus showed significant associations with MI risk, with odds ratios (ORs, 95% confidence interval) of 1.17(1.05-1.30), 1.18(1.05-1.32), and 1.14(1.02-1.28), respectively. Compared to subjects with blood group O, the ORs for blood group A, AB and B were 1.24 (95% CI, 1.08-1.43), 1.15 (95% CI, 0.95-1.39), and 1.10 (95% CI, 0.77-1.57), respectively. Subjects with non-O blood group had an adjusted OR for MI of 1.20 (95% CI, 1.05-1.37) when compared to subjects with O blood group after adjustment for age, sex, area of residence, smoking, alcohol consumption, physical activity, total calories, and family history of MI.

CONCLUSIONS:
Our results indicate both the consistency and disparity of ABO genetic effects on MI risk between Hispanics and Caucasians.
Abstract 16419: A Comparative Analysis of Prasugrel versus Ticagrelor on Rates of High On-Treatment Platelet Reactivity Following Switch From Clopidogrel Therapy
Authors: Rollini Fabiana , Cho Jung Rae , Franchi Francesco , Bhatti Mona , DeGroat Christopher , Taha Mohamad , Muniz-Lozano Ana , Singh Kamaldeep , Ferrante Elisabetta , Dunn Elizabeth C , Zenni Martin M , Guzman Luis A , Bass Theodore A , Angiolillo Dominick J
Published: July 2021

Background:
Clopidogrel is characterized by non-uniform pharmacodynamic (PD) effects leading to considerable rates of high on-treatment platelet reactivity (HPR), a marker of increased atherothrombotic risk. Prasugrel and ticagrelor have greater potency and more uniform PD effects compared with clopidogrel. The effects of switching from clopidogrel to prasugrel or ticagrelor and how this impacts HPR rates has been poorly explored.

Methods:
This was a prospective, randomized PD study conducted in patients with coronary artery disease on maintenance aspirin (81mg/qd) and clopidogrel (75mg/qd) therapy. Patients were randomized to switch to prasugrel (60mg loading dose/10mg maintenance dose qd) or ticagrelor (180mg loading dose/90mg maintenance dose bid) for 1 week. PD assessments were performed at 5 time points: before (while on clopidogrel) and 30 min, 2 hrs, 24 hrs and 1 week after switch. HPR was defined by a platelet reactivity index (PRI) > 50% assessed by VASP and platelet reaction unit (PRU) > 208 assessed by VerifyNow P2Y12 (VN).

Results:
A total of 110 patients were studied. HPR on clopidogrel therapy as defined by VASP-PRI was observed in 67.3% of the overall population. HPR rates were similarly distributed among patients subsequently randomized to prasugrel vs ticagrelor (69.8% vs 64.7%, p=0.57). After switching to prasugrel or ticagrelor, HPR rates significantly reduced as early as 30 min and continued to decrease consistently in both groups over the study time period. At 1 week, HPR was found in 13.7% and 15.6% of patients randomized to prasugrel and ticagrelor, respectively (p=0.80) (Figure). Parallel findings were observed when assessing HPR rates defined by VN-PRU (Figure).

Conclusions:
Switching from clopidogrel to a more potent P2Y
12
inhibiting agent significantly reduces HPR rates. Reduction in HPR rates occur to a similar extent between prasugrel and ticagrelor in both the acute and maintenance phases of therapy.
Abstract 16422: 4D Flow MRI Improves Assessment of Aortic and Pulmonary Peak Velocities in Patients With D-Transposition of Great Arteries Following Arterial Switch Operation
Authors: Jarvis Kelly , Schnell Susanne , Barker Alex , Vonder Marleen , Rose Michael , Carr James , Robinson Joshua D , Markl Michael , Rigsby Cynthia
Published: July 2021

BACKGROUND:
Pulmonary artery stenosis is the most common complication seen following the arterial switch operation (ASO) for D-transposition of the great arteries (DTGA). During follow-up, it is important to accurately detect peak velocity as an indicator of vessel narrowing. The purpose of this study was to compare peak velocity measurements by 4D flow MRI (4D flow) (with full volumetric coverage of aorta and pulmonary system) to those by standard 2D phase contrast MRI (2D PC) and Doppler echo.

METHODS:
4D flow and 2D PC were performed in n=14 subjects (age = 12.4 ± 7.6, range = 1 to 25) with DTGA s/p ASO. 3D segmentation of the aorta (Ao) and pulmonary arteries (PAs) was performed to isolate 4D flow velocities for these vessels (Figure a). The location and value of peak systolic velocity was determined inside volumes of interest for the ascending aorta (AAO), main (MPA), right (RPA) and left pulmonary arteries (LPA). RPA and LPA 2D PC data were not available in one patient. Contemporary echo data were available in 11 patients (11 AAO, 8 MPA, 6 RPA, 5 LPA).

RESULTS:
Peak velocity measurements by 4D flow were significantly higher than 2D PC in all regions (AAO: 1.51±0.61m/s vs. 1.15±0.24m/s, p = 0.016; MPA: 2.08±1.11m/s vs. 1.44± 0.61m/s, p = 0.004; RPA: 2.19±0.65m/s vs. 1.79±0.81m/s, p = 0.027; LPA: 2.08±0.85m/s vs. 1.74±0.70m/s, p = 0.014). Regression results indicated strong relationships between 4D flow and 2D PC (AAO: R2 = 0.46, p = 0.008; MPA: R2 = 0.69, p = 0.0002; RPA: R2 =0.50, p = 0.007; LPA: R2 = 0.74, p = 0.0001) (Figure b). No significant difference was found between peak velocities measured by 4D flow and echo (AAO: p = 0.32, MPA: p = 0.24, RPA: p = 0.91, LPA: p = 0.36) or by 2D PC and echo (AAO: p = 0.49, MPA: p = 0.62, RPA: p = 0.35, LPA: p = 0.066).

CONCLUSION:
4D flow outperformed 2D PC for detecting peak velocity in the Ao and PAs. No significant difference was found between peak velocities measured by 4D flow and echo. Further studies are warranted in a larger patient cohort to determine clinical impact.
Abstract 16451: Dose-Escalation Study Using Novel Continuous Flow Intracoronary Delivery of Allogeneic Cardiosphere-Derived Stem Cells: Is There a Threshold for Cell Therapy?
Authors: Tseliou Eleni , Dawkins James , Gallet Rpmain , Kreke Michelle , Smith Rachel , Middleton Ryan , Valle Jackelyn , Cingolani Eugenio , Kar Saibal , Marbán Linda , Makkar Rajendra , Marbán Eduardo
Published: July 2021

BACKGROUND:
Intracoronary (IC) infusion of cardiosphere-derived stem cells (CDCs) under stop-flow conditions has proven efficacious in producing myocardial regeneration in preclinical and clinical studies. However, the minimally-effective dose is not known, nor is it clear whether benefit is straightforwardly dependent on CDC dose.

OBJECTIVE:
To determine the dose-efficacy relationship of allogeneic CDCs in a large-animal chronic myocardial infarction (MI) model.

METHODS:
Escalating doses of allogeneic CDCs (3.125M, 6.25M, 12.5M, 25M; or vehicle as a control) were infused into the left anterior descending coronary artery using a nonocclusive guiding catheter in an anterior chronic MI minipig model. Magnetic resonance imaging (MRI) was used to assess structural and functional endpoints.

RESULTS:
CDCs were infused in a total of 25 animals under continuous flow at a rate of 1.25M CDCs/min. An additional 5 control animals underwent continuous flow of vehicle over 10 min. No animals experienced adverse events during or after the infusions. One month post therapy, ejection fraction (EF) was preserved at doses of 6.25M, 12.5M and 25M, but not with 3.125 M allo-CDCs or control (ΔEF = -6.7±0.9% in the placebo, -5.1±1.8% in 3.125M, -1.4±0.6% in the 6.25M, -2±1.4% in the 12.5M and -2.3±1.2% in the 25M group; p=0.04 by one way ANOVA for treatment effect). All doses of CDCs (except 3.125M) led to equivalent scar mass reductions, as assessed by MRI with Gd enhancement (p=0.0037 treated vs placebo, one-way ANOVA). Provocative electrophysiology testing at the end of the study revealed no enhanced arrythmogenic potential after cell therapy.

CONCLUSIONS:
Allogeneic CDCs can be safely administered with a non-occlusive method, over a wide dosage range. All doses >3.125M lead to enhanced preservation of left ventricular function and tissue remodeling, but to similar degrees. Our data reveal that CDCs work by a “threshold” effect that does not obey classical drug-receptor kinetics. This finding is consistent with the extraordinary ability of seemingly-homeopathic doses to exert large, lasting benefits.
Abstract 16460: Enhanced Trpc Channel-Mediated Ca2+ Influx in the Cells With Phospholipase C-δ1 Overexpression
Authors: Murakami Kazuo , Osanai Tomohiro , Tanaka Makoto , Nishizaki Kimitaka , Narita Ikuyo , Kinjo Takahiko , Tanno Tomohiro , Tomita Hirofumi , Okumura Ken
Published: July 2021

Background:
We recently showed that ergometrine induces coronary spasm in the mice with enhanced phospholipase C (PLC)-δ1 activity, which was detected in patients with coronary spasm (Circulation 2012), and PLC-mediated Ca2+ entry is involved in the genesis of coronary spams. We examined the role of enhanced PLC-δ1 in extracellular Ca2+ entry and its underlying mechanisms in human embryonic kidney (HEK)-293 cells and human coronary arteries smooth muscle cells (CASMC).

Methods and Results:
The cells were stimulated with acetylcholine (ACh) in a extracellular Ca2+-free condition, and the increase in intracellular free Ca2+ concentration ([Ca2+]i) after addition of extracellular Ca2+ was defined as Ca2+ influx. [Ca2+]i was measured by fura-2. In HEK-293 cells, ACh-induced Ca2+ influx (nM ) was 21±2 in the control and 52±6 in the cells with PLC-δ1 overexpression (p<0.05). ACh-induced Ca2+ influx in the cells with PLC-δ1 overexpression was suppressed by nifedipine in a dose-dependent manner but was partially by 36±13% at 10-5M (p<0.05), thereby even after treatment with nifedipine at 10-5M, ACh-induced Ca2+ influx was increased by 2.9±0.1 times by enhanced PLC-δ1 compared with the control (p<0.05). To clarify the role of diacylglycerol (DAG) in Ca2+ influx, the effect of blockers for DAG-activated transient receptor potential (TRPC) channel was examined. ACh-induced Ca2+ influx in the cells with PLC-δ1 overexpression was suppressed by 2-APB, an inhibitor of non-selective cation channel TRPC, in a dose-dependent manner, and was almost completely blocked by 89±12% at 10-4M (p<0.05). While TRPC3 siRNA did not affect ACh-induced Ca2+ influx (59±27 vs 75±23 nM, p=ns), TRPC6 siRNA suppressed Ca2+ influx to 37±28 nM (p<0.05). In human CASMC, ACh-induced Ca2+ influx was 41±11 in the control and 64±15 in the cells with PLC-δ1 overexpression (p<0.05). Like HEK-293 cells, pretreatment with nifedipine partially suppressed Ca2+ influx, whereas either 2-APB or TRPC6 siRNA almost completely blocked it.

Conclusion:
ACh-induced Ca2+ influx, mediated by both voltage-gated Ca2+ channels and non-selective cation channels TRPC6, is enhanced by PLC-δ1 overexpression. Inhibition of TRPC may be effective in enhanced PLC-δ1-mediated coronary spasm.
Abstract 16471: Illness Perception in Patients Hospitalized for Acute Coronary Syndrome
Authors: Suarez-Bagnasco Mariana , Estevez Ariel O , Higa Claudio , Monsalvo Maria Laura
Published: July 2021

Introduction:
Studies of Illness perception in patients with acute coronary syndrome (ACS) conducted in Canada and Finland showed that genetic factors, stress and lifestyle behaviors are the most common perceived cause of ACS (unstable angina, myocardial infarction). As illness perception is influenced by the personal experience of the illness and its management, as well as by cultural and social factors, we conducted a study to assess illness perception in patients with acute coronary syndrome in Argentina.

Methods:
Descriptive, cross-sectional, multicenter study. Adults over 18 years old hospitalized for ACS participated in the study. The day of discharge from the Coronary Care Unit, each subject completed a questionnaire generated and validated in Argentina aimed at assessing illness perception. Clinical data were collected by the treating physician at each participating institution.

Results:
109 patients between 33 and 84 years old (mean [SD] age = 61 [12] years, 70% male) were enrolled; 57% was diagnosed with ACS without ST-segment elevation and 37% was diagnosed with acute myocardial infarction (MI) with ST-segment elevation; in 6% the acute MI was indeterminate. Many patients attributed the heart disease to their traditional cardiovascular risk factors: 93% to hypertension, 81% to cholesterol, 71% to diabetes mellitus, 69% to physical inactivity, 67% to obesity, 63% to smoking. Only 30% of patients with a positive family history identified it as a risk factor. Stress, anxiety, and personality were identified as the cause for their heart disease in 71%, 64%, and 42% of patients, respectively. The majority of patients (74%) considered that they should improve the adherence to medications after discharge and 80% that should attend the medical follow-ups.

Conclusion:
Most patients identified their modifiable risk factors as causal for coronary heart disease. Only 30% of participants with a positive family history recognized it as a risk factor. A high percentage of patients recognized suboptimal behaviors in relation to medication adherence and medical follow-ups.
Abstract 16509: Young Long QT Syndrome Patients With KCNH2 Mutations Have Late Onset but Severe Symptoms
Authors: Ozawa Junichi , Ohno Seiko , Itoh Hideki , Makiyama Takeru , Horie Minoru
Published: July 2021

Introduction:
The long QT syndrome (LQTS) is one of the causes of sudden cardiac death in children. Although the risk factors for cardiac events depending on the genotype have been reported, age-related difference in phenotype remains unknown.

Objectives:
We aimed to clarify the age-and genotype-related clinical features in the young LQTS cohort (form 1 to 20y.o.).

Methods and Results:
This study comprised 101 symptomatic LQTS patients that were genotyped (male n=36, mean age 10.6±4.3). We excluded patients with multiple mutations. Fifty patients carried heterozygous mutations in KCNQ1, 48 in KCNH2 and 3 in SCN5A. LQTS-related cardiac events were classified into 3 categories; syncope, documented Torsades de pointes (TdP) and cardio-pulmonary arrest (CPA). Ninety patients experienced syncope, 7 were documented TdP and 4 suffered CPA. Figure shows a frequency histogram for the ages of first event in each genotype. The mean age of the onset in KCNH2 mutation carriers were significantly older (12.2±4.6y.o.) than those in KCNQ1 (9.2±3.5y.o., p<0.001). The numbers and mean ages of the patients suffered CPA were 1 in KCNQ1 (12y.o.), 2 in KCNH2 (10.5±3.5y.o.) and 1 in SCN5A (6y.o.). TdP was significantly more frequently documented in the patients with KCNH2 mutations (n=6, 13.7±3.3y.o.) than those with KCNQ1 mutations (n=1, 9y.o., p=0.029).

Conclusion:
In the young LQTS patients, therefore, KCNH2 mutation carriers showed a severer phenotype than those of KCNQ1, though their age of onset was older. These finding helped us to choose more appropriate preventive therapy depend on the age of onset and genotype.
Abstract 16511: EN-RAGE: A Novel Inflammatory Marker for Coronary Heart Disease
Authors: Ligthart Symen , Sedaghat Sanaz , Ikram M A , Hofman Albert , Franco Oscar H , Dehghan Abbas
Published: July 2021

Introduction:
Inflammation plays a key role in atherosclerosis. We hypothesized that uninvestigated inflammatory markers may predict the risk of coronary heart disease (CHD).

Methods:
We investigated the association of 16 inflammatory biomarkers with the risk of CHD in a random subset of 839 CHD free individuals in a prospective population-based cohort study. A Bonferroni corrected p-value of 3.1х10
-3
was used as a threshold of statistical significance. We additionally tested whether the association of any identified marker was independent of traditional CHD risk factors and previously studied inflammatory markers.

Results:
Mean age at baseline was 72.8 years. During a median follow-up of 10.6 years, 99 cases of incident CHD were observed. Among all novel inflammatory biomarkers, neutrophil derived human s100a12 (EN-RAGE) showed the strongest association with the risk of CHD (p-value 2.0х10
-3
). In the age and sex adjusted model, each standard deviation increase in the natural log-transformed EN-RAGE was associated with 37% higher risk of incident CHD (Hazard ratio (HR): 1.37; 95% confidence interval (CI) CI: 1.12 - 1.67). After further adjustment for established cardiovascular risk factors, the effect estimates attenuated slightly (HR: 1.30; 95% CI: 1.06 - 1.59). Adjustment for ten previously studied inflammatory markers did not attenuate the association (HR: 1.41; 95% CI: 1.12 - 1.77). Excluding individuals with prevalent type 2 diabetes, impaired kidney function or individuals using antihypertensive medication did not change the effect estimates.

Conclusions:
Our results highlight EN-RAGE as a novel inflammatory marker for CHD independent of traditional CHD risk factors and inflammatory markers, suggesting a specific inflammatory risk pathway for CHD.
Abstract 16517: Atrial Natriuretic Peptide as a Marker for Early Rule-Out of Acute Myocardial Infarction
Authors: Slagman Anna , Searle Julia , Holert Fabian , Vollert Jörn Ole , Muller Reinhold , Stockburger Martin , Müller Christian , Möckel Martin
Published: July 2021

Introduction:
Mid-regional pro-ANP is mainly synthesized in the atria of the heart and it′s secretion is stimulated by ischemia and distension of the myocardium.

Objective:
To assess the utility of ANP for rule out NSTEMI in combination with cardiac troponin in unselected patients who attend the Emergency Department (ED) with acute cardiac chief complaints.

Methods:
Patients with chest pain and dyspnea were enrolled over a period of 30 months in the Emergency Department (n=537). Patients with STEMI were excluded from the analysis as diagnosis is ECG- and not biomarker-based (n=18). Blood samples were drawn within 2 hours after admission. Gold-Standard diagnoses were adjudicated by an independent cardiologist. ANP was measured using the BRAHMS Kryptor MR-proANP assay. The lower limit of detection is 2.1 pmol/l. The 97.5
th
percentile of a normal population is 86.2 pmol/l and was applied as a cut-off value in this analysis. Troponin I was measured using the Stratus CS and a cut-off value of 0.1 μg/L was applied. Variables are shown as median (IQR) and 95%-CIs.

Results:
The median ANP-value in all patients (n=519) was 135 pmol/l. Patients with NSTEMI (n=58) had significantly higher ANP-values (244/104-350 pmol/l) as compared to patients with other diagnoses (126/74-256; p<0.0001). In ROC-analysis ANP had an area under the curve of 0.648 (CI:0.582-0.715) for the diagnosis of NSTEMI. Of all patients, 74.2% were troponin negative at admission (n=385). Of these patients, 32.2% (n=124) were also ANP negative. The prevalence of AMI in this subgroup was 1.6% (n=2). The NPV for the combination of troponin and ANP was 98.4% (CI: 94.3-99.8%) and thus higher than for both markers alone (figure 1). In combination with Copeptin, the NPV increased to 100% (CI: 96.3-100%).

Conclusions:
ANP has potential for early rule-out of AMI in combination with troponin and, due to a different pathophysiological stimulus, it might be used as part of a triple-marker strategy with copeptin and troponin.
Abstract 16529: Intracoronary Infusion of GCSF-Mobilized Human CD34+ Cells Preserves Left Ventricular Function and Prevents Infarct Expansion in a Swine Model of Acute Myocardial Infarction
Authors: Fujita Yasuyuki , Kinoshita Makoto , Akimaru Hiroshi , Akimaru Erika , Komatsu Miki , Furukawa Yutaka , Asahara Takayuki , Kawamoto Atsuhiko
Published: July 2021

Background:
A phase I clinical trial revealed the safety and potential efficacy of intracoronary (i.c.) infusion of bone marrow (BM) CD34+ cells in patients with acute myocardial infarction (AMI). The final results of the “PreSERVE AMI” randomized phase II trial will be obtained this year. Despite such clinical development, CD34+ cell therapy for AMI has been preclinically investigated in the rat and mouse models, but not large animals.

Methods:
AMI was induced by 60 min-balloon inflation and reperfusion in the left anterior descending artery of the farm swine. One week after AMI, swine were randomly allocated to receive i.c. infusion of 2х105/kg GCSF-mobilized human CD34+ cells (cell group, n=8) or saline (control group, n=7). Immunosuppression was maintained by intramuscular injection of cyclosporine daily from week 1 to 5. Magnetic resonance imaging was performed to assess cardiac function and infarct size at week 1 and 5. All swine were sacrificed at week 5. Chemical staining for isolectin B4 was performed to detect capillaries in the cardiac tissue.

Results:
Left ventricular ejection fraction (LVEF) significantly increased in cell group (42.9±5.2 at week 1 to 48.5±4.1% at week 5, p<0.05) but not control group (47.6±2.4 to 44.8±3.5%, p=NS). LV end-systolic volume (LVESV) decreased in cell group (38.3±4.9 to 31.4±5.3 ml, p<0.01) but not control group (35.4±5.4 to 37.7±5.4 ml, p=NS). Regional wall thickening (RWT) in the border zone increased in cell group (30.8±14.9 to 45.5±10.4%, p<0.01) but not control group (37.2±16.4 to 26.4±9.3%). Infarct size by delayed enhancement increased in control group (16.8±7.5 to 22.35±6.4% of LV mass, p<0.05) but not cell group (20.5±10.2 to 20.87±8.0%). Changes in LVEF, LVESV and RWT between week 1 and 5 were better preserved in cell group than control group (p<0.05, 0.05 and 0.01, respectively). Histological capillary density in border zone was greater in cell group than control group (1698.0±474.2 vs 998.6±269.6/mm2, p<0.01).

Conclusions:
Human CD34+ cell therapy may preserve global and regional LV function and prevent infarct expansion through enhancing neocapillary formation in swine with AMI. The favorable outcomes would support the further clinical development of the cell-based therapy in patients with AMI.
Abstract 16571: Temporal Release Pattern of Copeptin and Troponin in Patients With Suspected ACS and Spontaneous Acute Myocardial Infarction
Authors: Slagman Anna , Searle Julia , Holert Fabian , Müller Christian , Möckel Martin
Published: July 2021

Introduction:
Copeptin, a surrogate marker for vasopressin has been shown to have potential for the early rule-out of acute myocardial infarction in combination with cardiac troponin. The temporal release pattern of copeptin in spontaneous AMI has not been investigated until now at more than three time-points.

Objective:
To investigate the temporal release pattern of copeptin and cardiac troponin in spontaneous acute myocardial infarction at six time-points from ambulance until 12-36 hours.

Methods:
Patients with suspected ACS and acute symptom onset were enrolled in this study. Blood samples were collected on the ambulance, at admission and after 2, 4, 6 and 12-36 hours. Gold-Standard diagnoses were adjudicated according to the third definition of myocardial infarction by a cardiologist. Copeptin (BRAHMS Kryptor Copeptin us) and troponin T (Roche Diagnostics, Elecsys) were measured in heparin plasma.

Results:
Overall 93 patients were enrolled. The most frequent diagnosis was STEMI (n=37, 39.8%), 20 patients were diagnosed with NSTEMI (21.5%), 20 patients had UAP (21.5%) and 16 patients were diagnosed with other, non-ACS diagnoses (17.2%). The release kinetic of copeptin differed between different diagnoses: patients with AMI had significantly higher values at admission as compared to patients with UAP and other diagnoses (figure 1 A).

Troponin values on the ambulance were low in all patients but increased over time in patients with STEMI and NSTEMI (figure 1B).

Conclusions:
In early presenters with ACS copeptin and troponin show typical temporal release pattern; the very early rise and decrease within 12-36h of copeptin in spontaneous AMI has been shown for the first time. The pathophysiological stimulus for the copeptin-release in spontaneous AMI should be further investigated.
Abstract 16592: The Diamond-Forrester Criterion Significantly Overestimates the Risk of Obstructive Coronary Artery Disease in Patients Presenting to the Emergency Department With Low-Risk Chest Pain
Authors: Lecher Todd , Davidson William R , Foy Andrew
Published: July 2021

Introduction:
We sought to (1) classify patients who underwent stress echocardiography in an emergency department observation unit based on their pretest probabilities of obstructive CAD using the Diamond-Forrester criterion, (2) to compare observed versus expected frequencies of obstructive CAD based on the Diamond-Forrester risk categories of low (<25%), intermediate (25-75%), and high (>75%) pretest probability of disease, and (3) to test the association of traditional cardiovascular risk factors (age, gender, hypertension, diabetes, high cholesterol, and smoking) with obstructive CAD.

METHODS:
Retrospective review of the electronic medical record for patients who presented to the emergency department with chest pain and underwent observation followed by stress echocardiography between the period January 1, 2012 to December 31, 2012. Patients were classified as low, intermediate, or high risk for obstructive CAD using the Diamond-Forrester criterion. Main outcome measures were stress echocardiography results as well as receipt of cardiac catheterization and results.

RESULTS:
A total of 504 patients were included in the final analysis. Overall, 4.8% had a positive stress test and only 1.2% had angiographic evidence of obstructive CAD. In each category of risk, the observed frequency of obstructive CAD was significantly lower than expected. Having a high pretest probability as defined by the Diamond-Forrester criterion was significantly associated with obstructive CAD. Age, gender, diabetes, hypertension, high cholesterol, and smoking were not independently associated with evidence of obstructive CAD; nor were any composites of these risk factors.

CONCLUSIONS:
The traditional Diamond-Forrester criterion significantly overestimates the probability of obstructive CAD in ED observation unit patients. Reliance on the Diamond-Forrester criterion and other traditional risk factors associated with obstructive CAD in the outpatient setting could lead to faulty Bayesian reasoning, overuse of non-invasive imaging, and improper interpretation of test results in an ED population of low-risk chest pain patients. Further work is required to determine an optimal risk-assessment strategy for this patient population.
Abstract 16599: Impaired Right Ventricular Contractile Reserve During Exercise in Endurance Athletes With Right Ventricular Arrhythmias
Authors: Claessen Guido , La Gerche Andre , Voigt Jens-Uwe , Dymarkowski Steven , Van Hees Luc , Van Cleemput Johan , Claus Piet , Heidbuchel Hein
Published: July 2021

Introduction:
Ventricular arrhythmias in endurance athletes (EAs) frequently originate from a mildly dysfunctional right ventricle (RV). We evaluated whether RV dysfunction in EAs with ventricular arrhythmias of RV origin (EA-VAs) becomes more apparent during exercise than at rest.

Methods:
Ten healthy EAs, 7 healthy non-athletes (NAs) and 17 EA-VAs (8 with ICD) first underwent cardiopulmonary exercise testing to determine maximal power (Pmax). Then, exercise echocardiography was performed at 25%, 50% and 66% of Pmax to measure the RV end-systolic pressure-area ratio (ESPAR), a surrogate of RV contractility, which was calculated as systolic pulmonary artery pressure/RV end-systolic area. Finally, all subjects without ICD underwent cardiac MRI during supine bicycle exercise at similar workloads with simultaneous invasive pulmonary artery pressure measurement to determine the RV end-systolic pressure-volume ratio (SP/ESV).

Results:
At rest, RV ESPAR was similar in EA-VAs relative to NAs (P=0.1), although slightly lower than in NAs (P=0.02). During exercise, EA-VAs had an impaired increase in RV ESPAR compared to both EAs and NAs (interaction P<0.0001; Figure 1A). Also the slopes of RV ESPAR to absolute workload (in Watts) were lower in EA-VAs than in EAs and NAs (P<0.0001) and correlated highly with the slopes of RV SP/ESV to workload obtained by MRI and invasive pressure measures (R=0.75; P<0.0001). Figure 1B shows that resting and peak exercise RV ESPAR cutoffs of 1.4 and 3.9 mmHg/cm
2
had a sensitivity of 77% and 79% and specificity of 80% and 100%, respectively, to identify EA-VAs.

Conclusion:
EA-VAs have impaired RV contractility which is evident during exercise but hardly at rest. This strengthens the association between RV arrhythmias and functional impairment. Our data suggest that exercise echocardiography is sufficiently accurate to determine RV contractile reserve in a non-invasive manner and may assist in risk stratification of RV remodeling in EAs.
Abstract 16626: Digital Health Interventions Improves Cardiovascular Risk Factors and Reduces Rehospitalizations After Usual Cardiac Rehabilitation
Authors: Widmer Robert J , Allison Thomas , Lerman Lilach , Lerman Amir
Published: July 2021

Introduction:
Cardiovascular disease (CVD) is the leading cause of morbidity/mortality in the US. Despite being a class 1A evidence-based recommendation, secondary prevention efforts in the period following cardiac rehabilitation (CR) lack a proven and successful intervention. A previously validated digital health intervention (DHI) delivered Mayo Clinic’s CR, including educational material, tracking CVD indices, and diet/exercise adherence, for 3 months after usual CR.

Hypothesis:
We hypothesized DHI use would improve CVD risk factors and rehospitalizations/ emergency department (ED) visits.

Methods:
Patients undergoing usual Mayo Clinic CR were recruited to use the application following usual CR (n=17) and compared to a similar cohort undergoing standard post-CR care, but not assigned to the application (n=11). DHI patients performed daily informational tasks, entered their own risk factor information (weight, blood pressure (BP), glucose, lipids, physical activity, and diet) at baseline and for three months post-CR. Changes in risk factors, re-hospitalizations/ED visits were assessed after three months.

Results:
There were no differences in baseline demographics between the two groups. There was no difference in weight change between the two groups during the three months of usual CR, yet in the three months following usual CR the DHI group had significant reductions in weight (-2.5±3.8 kg, p=0.04) and systolic BP (-12.6±12.4 mmHg, p=0.001) compared to the control group. The DHI group also showed significantly lower rate of rehospitalizations/ED visits (-28%, p=0.04, Figure).

Conclusions:
A DHI post-CR program can enhance secondary prevention strategies compared to standard post-CR care by augmenting weight and BP reduction and reducing the healthcare burden of repeat CVD events. This study thus supports development and implementation of DHI programs.
Abstract 16685: Depletion of Circulating CD34+/KDR+ Cells in Type 2 Diabetes is Associated With Glycemic Control
Authors: Zafar Nagma , Krishnasamy Sathya S , Shah Jasmit , McCracken James , Holden Candice R , DeJarnett Natasha K , Abplanalp Wesley T , Hill Bradford , Conklin Daniel , O’Toole Timothy , Rai Shesh , Bhatnagar Aruni
Published: July 2021

Background and Hypothesis:
Circulating levels of endothelial progenitor cells have been found to be predictive of cardiovascular events and mortality. Although the levels of these cells reflect overall cardiovascular disease (CVD) risk, studies assessing their association with major CVD factors - hypertension, dyslipidemia and diabetes have yielded inconsistent results and the mechanisms contributing to EPC depletion remain unknown. We hypothesized that EPC depletion occurring in diabetes is mediated in part by hyperglycemia or insulin resistance.

Methods:
Circulating levels of progenitor cells were measured by flow cytometry in 108 diabetic or non-diabetic subjects recruited from the University of Louisville Health System. Reactive hyperemia index (RHI) was measured by the EndoPAT. Demographic information was acquired and blood, plasma and urine were used for biochemical analyses. Subjects were divided into high and low EPC count groups using the median split. Data was analyzed using a Chi-square test, a two-sample rank sum test, and univariable and multivariable logistic regressions.

Results:
Levels of CD34
+
/KDR
+
/CD14
−
/CD16
−
cells (EPCs) were associated with the diagnosis of diabetes (p=0.04), but not with other demographic covariates, hypertension or dyslipidemia. Levels of CD34
+
, AC133
+
and CD34
+
/AC133
+
/CD45
+
cells also displayed significant association with diabetes (p=0.038, 0.014 and 0.038 respectively). RHI was strongly associated with diabetes (p<0.0001) hypertension and dyslipidemia, however, no significant associations were observed between RHI and EPCs. EPC levels were inversely associated with HbA1C (p=0.047) and fasting blood glucose, but not with insulin levels or the HOMA-IR score. In the complete model, the association between EPCs and diabetes was strengthened by the inclusion of RHI, indicating more robust EPC depletion in those with endothelial dysfunction.

Conclusion:
Circulating EPC levels are a robust index of long-term glycemic control and are associated with hyperglycemia rather than contemporaneous insulin levels or endothelial dysfunction. These findings may help in prognosis and early identification of CVD risk in patients with diabetes, independent of other risk estimates.
Abstract 16687: Abnormal Peripheral Muscle Oxygenation During Submaximal Exercise Contributes to Exercise Intolerance in Pulmonary Arterial Hypertension
Authors: Malenfant Simon , Potus François , Mainguy Vincent , Neyron Anne-Sophie , Leblanc Evelyn , Malenfant Mathieu , Tremblay ève , Breuils-Bonnet Sandra , Maltais François , Saey Didier , Bonnet Sébastien , Provencher Steeve
Published: July 2021

Introduction:
Pulmonary arterial hypertension (PAH) is a vascular remodeling disease leading to right ventricular failure. Despite the most modern therapies, most patients display persistent and significant exercise intolerance. Many observations suggest that exercise limitation in PAH is not simply due to pulmonary hemodynamic impairment, but that other determinants intrinsic to the skeletal muscle are involved.

Hypothesis:
We hypothesized that O2 delivery to skeletal muscles during exercise is impaired in PAH independently of cardiac output.

Methods and Results:
Ten PAH patients performed a submaximal exercise at 70% of their peak workload (mean workload = 58 (15) W). Ten healthy controls performed the same exercise at the same workload as the PAH patients with whom they were paired. The increase in muscle deoxyhemoglobin concentration [HHb] (near-infrared spectroscopy, ISS) of the dominant quadriceps was significantly higher in PAH patients compared to healthy controls (29.6 (3.7) vs 9.7 (2.5) %; p<0.01) at the end of the submaximal exercise. This was not related to differences in cardiac output increases during exercise (+4.0 (0.7) vs +3.2 (0.4) L/min; p=0.29) (Nexfin BMEYE) or hemoglobin level (138.4 (2.4) vs 138.1 (3.7) g/L; p=0.94) for PAH patients and controls, respectively. Conversely, exercise-induced arterial O2 desaturation was more pronounced for PAH patients (-5.5 (1.8) vs -0.2 (0.6) %; p=0.03). Adding O2 supplementation did not significantly modified end-exercise muscle [HHb] (p=0.53), cardiac output increases (p=0.72) and arterial O2 desaturation (p=0.18). Quadriceps muscle biopsy confirmed that PAH patients had lower capillarity density compared to healthy controls (202 (27) vs 304 (23) #cap/mm2; p=0.01) that correlated with end-exercise muscle [HHb] (R2=0.37; p<0.01). Finally, muscle [HHb] during submaximal exercise correlated with VO2 max (R2=0.65; p<0.01) and 6 minutes walk test distance (R2=0.54; p=0.01).

Conclusions:
Our results demonstrate that PAH patients exhibit a lower skeletal muscle capillarity density that contributes to inadequate muscle O2 supply during exercise and exercise intolerance.