bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac Myocyte Gq Signaling Decreases Cardiac Function During Chronic High Blood Pressure Through Cardiac Remodeling
Authors: Harris David M
Published: July 2021

Abstract 290

David M Harris, Thomas Jefferson University, Philadelphia, PA; Xiongwen Chen, Temple University, Philadelphia, PA; Stephanie Pesant, Heather I Cohn, Thomas Jefferson University, Philadelphia, PA; Scott M MacDonnell, Temple University, Philadelphia, PA; Mattieu Boucher, Korin Faulkner, Maggie Shapiro, Patrick Most, Thomas Jefferson University, Philadelphia, PA; Steven R Houser, Temple University, Philadelphia, PA; Walter J Koch, Andrea D Eckhart, Thomas Jefferson University, Philadelphia, PA

David M Harris, 2007 Finalist and Presenting Author
Phosphodiesterase-5 is Highly Expressed in the Hypertrophied Human Right Ventricle and Acute Inhibition Causes Increased Contractility via cGMP-Inhibition of Phosphodiesterase-3
Authors: Nagendran Jayan
Published: July 2021

Abstract 278

Jayan Nagendran, Stephen L Archer, Daniel Soliman, Vikram Gurtu, Al Haromy, Ivan M Rebeyka, David B Ross, Peter E Light, Evangelos D Michelakis, University of Alberta Hosp, Edmonton, AB, Canada

Jayan Nagendran, 2007 Finalist and Presenting Author
A Prospective Comparison of NMR-Measured LDL Particle Number, Apolipoprotein B100, and Standard Lipids with Incident CHD in 27,673 Initially Healthy Women
Authors: Mora Samia
Published: July 2021

Abstract 3481

Samia Mora, Brigham And Womens Hosp, Boston, MA; James Otvos, LipoScience, Inc., Raleigh, NC; Julie E Buring, Brigham And Women’s Hospital, Boston, MA; Nader Rifai, Boston Children’s Hosp, Boston, MA; Paul M Ridker, Brigham And Women’s Hospital, Boston, MA

Samia Mora, 2007 Finalist and Presenting Author
2008 Sol Sherry Distinguished Lecture in Thrombosis—Platelet Adhesion in Acute Arterial Thrombosis
Authors: Ruggeri Zaverio M.
Published: July 2021

Platelet adhesion is an essential function in response to vascular injury, through which single platelets bind to specific membrane receptors onto cellular and extracellular matrix constituents of the vessel wall and tissues initiating thrombus formation that arrests hemorrhage and permits wound healing. Pathological conditions that cause vascular alterations and blood flow disturbances may turn this defense process into a disease mechanism resulting in arterial occlusion, mostly in atherosclerotic vessels of the heart and brain. Besides their relevant role in hemostasis and thrombosis, platelet adhesive properties are central to a variety of pathophysiological processes that extend from inflammation to immune-mediated host defense and pathogenic mechanisms as well as cancer metastasis. All these activities depend on the ability of platelets to circulate in blood as sentinels of vascular integrity, adhere where alterations are detected, and signal the abnormality to other platelets and blood cells. In this respect, therefore, platelet adhesion to vascular wall structures, to one another (aggregation), or to other blood cells represents different aspects of the same fundamental biological process. Novel concepts and tools are being developed to advance our knowledge of the mechanisms through which platelets respond to vascular injury. Of particular interest are specific microparticles endowed with selective targeting properties conferred by recombinant adhesive domains that may be used for targeting areas of the vasculature with thrombogenic potential and for diagnostic purposes. Particles with such specific adhesive properties may also be used for the local delivery of anti-thrombotic drugs.
Genetic Fate Mapping Identifies Second Heart Field Epicardial Progenitor Cells as a Source of Adipocytes in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Lombardi Raffaella
Published: July 2021

Abstract 473

Raffaella Lombardi, Jinjiag Dong, Gabriela Rodriguez, Achim Bell, Univ of Texas Hlth Sci Cnt, Houston, TX; Tack Ki Leung, Montreal Heart Inst, Université de Montréal, Montreal, Quebec, QC, Canada; Robert J Schwartz, Inst of Biotechnology, Texas A&M University, Houston, TX; James T Willerson, Univ of Texas Hlth Sci Cnt, Houston, TX; Ramon Brugada, Montreal Heart Inst, Université de Montréal, Houston, TX, Canada; Ali J Marian, Univ of Texas Hlth Sci Cnt, Houston, TX

Raffaella Lombardi, 2008 Finalist and Presenting Author
Allogeneic Mesenchymal Stem Cells in Cellular Cardiomyoplasty: Mechanisms of Cardiac Repair
Authors: Hatzistergos Konstantinos
Published: July 2021

Abstract 486

Konstantinos E. Hatzistergos, Henry Quevedo, Behzad N. Oskouei, Qinghua Hu, Ramesh Mazhari, Juan P. Zambrano, David Valdes, Gary S. Feigenbaum, Jose R. Rodriguez, Irene S. Margitich, Jeffrey M. Zimmet, Univ of Miami, Miami, FL; Concepción Revilla, INIA, Madrid, Spain; Alan W. Heldman, Ian McNiece, Joshua M. Hare, Univ of Miami, Miami, FL

Konstantinos Hatzistergos, 2008 Finalist and Presenting Author
Non-invasive MRI Assessment of Coronary Endothelial-Dependent Vasoreactivity
Authors: Hays Allison
Published: July 2021

Abstract 1077

Allison G. Hays, Glenn A. Hirsch, Sebastian Kelle, Gary Gerstenblith, Matthias Stuber, Robert G. Weiss, Johns Hopkins, Baltimore, MD

Allison Hays, 2008 Finalist and Presenting Author
Effect of Hypercholesterolemia on Myocardial Necrosis and Apoptosis in Response to Ischemia Reperfusion Injury
Authors: Osipov Robert
Published: July 2021

Abstract 1098

Robert M Osipov, Cesario Bianchi, Jun Feng, Yuhong Liu, Richard T Clements, Neel Sodha, Frank W Sellke, Beth Israel Deaconess Medical Ctr, Boston, MA

Robert Osipov, 2008 Finalist and Presenting Author
Chest Pain and Dyspnea in a Pregnant Woman With a Prosthetic Valve
Authors: Ahmed Jameel
Published: July 2021

Abstract 1120

Jameel Ahmed, George Philippides, Michael Klein, Boston Univ Medical Ctr, Boston, MA

Jameel Ahmed, 2008 Finalist and Presenting Author
Abstract 5820: The Clinical Value of Absolute Quantification of Myocardial Perfusion in The Detection of Coronary Artery Disease. A Study Using Positron Emission Tomography to Detect Multi-vessel Disease
Authors: Kajander Sami , Ukkonen Heikki , Joutsiniemi Esa , Mäki Maija , Saraste Antti , Ala-Knuuttila Erja , Pietilä Mikko , Airaksinen Juhani , Hartiala Jaakko , Saraste Markku , Knuuti Juhani
Published: July 2021

Background: Perfusion imaging is standard technique in the detection of CAD. However, the analysis is based on assessment of relative perfusion defects that has known limitations in the detection of multi-vessel disease. Typically only the most severe perfusion abnormalities are detected but not less severe defects or balanced disease. PET measures myocardial perfusion in absolute terms potentially being able to avoid these drawbacks but the value of quantitation has not been shown in clinical studies.

Aims: To evaluate the accuracy of absolute quantification of myocardial perfusion in the diagnosis and the detection of multivessel CAD.

Patients and methods: 83 consecutive patients with moderate (30–70%) pretest likelihood of CAD were enrolled. PET perfusion imaging at rest and during adenosine stress were performed using O-15-water. The studies were analyzed using validated quantitative model and software. Both standard relative perfusion images and images that were scaled to known absolute scale (0.0–3.5 ml/min/g) were produced. The images were analyzed by two experienced readers blinded to clinical data, image scaling and invasive coronary angiography (ICA). The regions were classified as normal (>70% of uptake), mildly abnormal (50–70%) and severely abnormal (< 50%) in each vascular territory and compared against ICA.

Results: The PPV, NPV and accuracy of absolute perfusion in the detection of any CAD were 87%, 97%, 92% respectively. The corresponding values in the detection of multi-vessel disease were 94%, 96% and 95%. When standard relative images were used the respective values for multi-vessel disease were 33%, 69% and 60% against ICA. Relative analysis was able to detect only 39% of patients with multi-vessel disease. In addition, regional perfusion was often (31%) falsely interpreted as multi-vessel disease while preserved absolute perfusion was able to exclude significant stenoses.

Conclusions: The measurement of myocardial perfusion in absolute terms has significant impact on the interpretation of myocardial perfusion. Standard relative analysis is able to detect only small fraction of patients with multi-vessel disease and also quite commonly variability in perfusion is falsely interpreted as a sign of multi-vessel disease.
Abstract 5854: Serial Assessment of Pulsatile and Non-Pulsatile Left Ventricular Assist Devices on Left Ventricular Unloading
Authors: George Robert S , Yacoub Magdi H , Webb Carole , Bowles Christopher , Dean Robert , Hedger Mike , Dreyfus Giles , Khaghani Asghar , Birks Emma J
Published: July 2021

Pulsatile and continuous flow left ventricular assist device (LVAD)s combined with pharmacological agents have been used to bridge patients with end-stage dilated cardiomyopathy (DCM) to recovery. The aim of this study was to compare the effects of pulsatile versus continuous flow LVADs on left ventricular (LV) unloading. Unloading was assessed by echocardiography at 1, 3 and 6 months in 50 non-ischaemic DCM patients with LVADs. 29 patients received a pulsatile volume displacement pump (HeartMate XVE (HM I group); Thoratec Corp.) and 21 patients received a continuous-flow rotary pump (HeartMate II (HM II group); Thoratec Corp.). Parameters measured included end-systolic and end-diastolic diameters (ESD and EDD) and ejection fraction (EF). There was no difference in pre-implantation data between the two groups. At 1 month post device implantation, HM I patients showed significantly greater LV unloading compared to HM II patients (ESD 30.6±10, EDD 44±9.7, EF 64.8±14.5 vs 41.5±10.7, 50.9±9.7, 45.5±15.9, respectively), but there was no difference in LV unloading at 3 or 6 months (table 1

). In the patients recovered with HM I (n=16) there was a lower ESD and higher EF compared to those with HM II (n=7) at 1 month. No difference was seen at 3 or 6 months (table 2

). HM I XVE provided a better degree of LV unloading compared to HM II at 1 month of LVAD support. At three and six months of LVAD support both devices provided an equivalent degree of LV unloading.

Table 1.

Comparison of LV unloading between HM I and HM II patients.

Table 2.

Comparison of LV unloading between HM I and HM II recovered patients
Abstract 5880: Serum Resistin Concentrations and Risk of New Onset Heart Failure in the Elderly
Authors: Georgiopoulou Vasiliki V , Kalogeropoulos Andreas P , de Rekeneire Nathalie , Rodondi Nicolas , Smith Andrew L , Hoffmann Udo , Kanaya Alka , Newman Anne B , Kritchevsky Stephen B , Vasan Ramachandran S , Wilson Peter W , Harris Tamara B , Butler Javed
Published: July 2021

Resistin, a novel adipocytokine, is associated with inflammation and insulin resistance; both mechanisms are known to increase risk for heart failure (HF). We studied 2904 older persons without HF (age 73.3±2.8 years, 47.9% men, 58.6% whites) enrolled in the Health ABC study who underwent serum resistin measurements at baseline. Participants were divided into groups based on tertiles of resistin concentrations and rates of incident HF (defined as hospitalization for new onset HF) were compared by Cox proportional hazards models. After 7.1 year median follow-up 252 participants (8.7%) developed HF. Increasing resistin concentrations were significantly associated with increasing incident HF rates (Figure 1

). After adjusting for baseline differences (including body mass index) and predictors of incident HF (age, coronary disease, smoking, blood pressure, heart rate, serum glucose, creatinine, and albumin concentrations, and left ventricular hypertrophy), serum resistin concentrations were independently associated with incident HF [highest vs. lowest tertile hazard ratio (HR) 1.96, 95% confidence interval (CI) 1.35–2.82). Further adjustment for markers of inflammation (Creactive protein, interleukin-6, and tumor necrosis factor α) and of insulin resistance (fasting insulin level and hemoglobin A1c) only moderately attenuated this association which remained significant (HR 1.67, 95% CI 1.13–2.60). These findings were consistent in both sexes and among whites and blacks. High serum resistin concentrations are independently associated with increasedrisk for HF. Further studies are needed to confirm these findings.
Abstract 5881: Influence Of Cardiac Inflammation And Extracellular Matrix Regulation On Diastolic Dysfunction In Patients With Heart Failure With Normal Ejection Fraction
Authors: Westermann Dirk , Kasner Mario , Lettau Olga , Noutsias Micheal , Schultheiss Heinz-Peter , Tschöpe Carsten
Published: July 2021

Aims: One of the hemodynamic mechanisms underlying heart failure with normal EF (HFNEF) is increased LV stiffness. In order to clarify the pathological changes leading to increased stiffness we investigated the left ventricular (LV) function using pressure-volume loops under basal conditions and during atrial pacing and investigated endomyocardial biopsies of patients with HFNEF.

Methods: In 36 patients with HFNEF and 8 controls pressure volume loops were measured under basal conditions and during atrial pacing. Furthermore, endomyocardial biopsies were analyzed for changes in the extracellular matrix regulation, cardiac inflammation and changes in the titin isoforms.

Results: Patients with HFNEF had an increased LV diastolic stiffness (+350%) compared to controls. During atrial pacing, stroke volume decreased (−35%) due to a leftward shift of the PV loops. This was associated with increased collagen content in cardiac biopsies (+380%), which blunted their cardiac output response to enhanced cardiac demand. This may explain the exercise intolerance in HFNEF patients. The total collagen correlated with cardiac stiffness in the HFNEF group (r2=0.69). This was associated with increased mRNA levels of the pro fibrotic TGF-b. Furthermore, the collagenase matrix metalloproteinases (MMP) 1 was not changed while TIMP-1 was increased (+150%), which supposes a decrease in collagen degradation in HFNEF. Nevertheless, MMP 2 was increased (+160%). This MMP is also associated with inflammation, and coherently, we investigated cardiac inflammation. We documented increased cardiac inflammation by an increment of adhesion molecules (ICAM +55%) and invading cells (CD11b cells +250%) in the cardiac tissue of HFNEF patients compared to controls. Interestingly, there was no change in titin isoforms between both groups.

Conclusion: Patients with HFNEF have increased diastolic stiffness leading to an impairment of the Frank-Starling mechanism during atrial pacing. Since increased stiffness correlated with the cardiac collagen content, changes in the ECM regulation might be important for the development of HFNEF and invading cells triggering cardiac inflammation might further participate in this pathophysiology.
Abstract 5892: Therapy For Device-determined Ventricular Arrhythmias Decrease As Biventricular Pacing Percentage Increases In Heart Failure Patients
Authors: Koplan Bruce A , Kaplan Andrew J , Jones Paul W , Seth Milan , Christman Shelly A
Published: July 2021

Introduction:
CRT-D improves cardiac function and quality of life, and decreases HF hospitalization and death for many patients. However, impact on therapy delivered for ventricular arrhythmias is less clear.

Methods:
Device-determined VT and VF episodes with therapy (n = 1835) from CRT-D patients in two trials (CRT RENEWAL & REFLEX; n = 1698) were analyzed in a post hoc fashion. Patients were divided into lifetime biventricular (BiV) pacing percentage quartiles. Zero-inflated Poisson regression models were used to evaluate impact of pacing on VT/VF incidence and frequency, adjusting for baseline covariates including lifetime ATR mode switch percentage.

Results:
Patient characteristics: 69 ± 11 years, 73% male, 68% CAD. Dividing patients in quartiles resulted in the following pacing breakdown: 0–92% (n = 445), 93–97% (n = 445), 98–99% (n = 482), and 100% (n = 326). There were no differences in gender, NYHA, or history of diabetes, MI, CAD or hypertension among the groups. Patients paced 0–92% and 93–97% had similar VT/VF therapy incidence (24.72% vs. 24.27%) and frequency (17.05% vs. 16.00%). Patients paced 98–99% had lower VT/VF therapy incidence (15.15%) than patients paced ≤ 97% (p < 0.001) but similar frequency after adjusting for incidence. Patients paced 100% had similar VT/VF therapy incidence (13.80%) and frequency (6.45%) to patients paced 98–99%. The figure

shows the time to first therapy for VT/VF.

Conclusions:
For CRT-D patients in this analysis, incidence and frequency of therapy delivered for VT/VF is significantly decreased when lifetime BiV pacing percentage is above 97%.
Abstract 5895: The Impact of Response to Cardiac Resynchronization Therapy on Ventricular Arrhythmic Events
Authors: Ando Kenji , Soga Yoshimitsu , Arita Takeshi , Shirai Shinichi , Goya Masahiko , Iwabuchi Masashi , Yokoi Hiroyoshi , Yasumoto Hitoshi , Nosaka Hideyuki , Nobuyoshi Masakiyo , Shizuta Satoshi , Doi Takahiro , Kimura Takeshi , Kit Toru
Published: July 2021

Background: It’s well known that cardiac resynchronization therapy (CRT) is effective to reduce heart failure hospitalization. However, the impact of response to CRT on ventricular arrhythmic events is not well established.

Methods: We investigated 216 pts received CRT in two institutions (age 69.3+/−10.8 years, NYHA class 3.1+/−0.5, LVEF 25.8+/−7.4%, LVEDD 62.1+/−8.3mm, pre QRS duration 158+/−32ms, AF 19.4%, ischemic heart disease 33.3%, CRT-D 51.3%) and divided into two groups, Responders (n=145, 67.1%) and Non-responders (n=71, 32.9%). CRT responder was defined as improvement of LVEF > or =5%, or reduction of LVEDD > or = 5mm at 3–6 month echo data. Long-term ventricular arrhythmic events (ventricular tachycardia: VT, ventricular fibrillation: VF and sudden cardiac death: SCD) were obtained. Kaplan-Meier curve were draw and Long-Rank test was used to compare event rates of two groups.

Results: Mean follow up periods was 19.3 +/−12.7 months. Event free survival rates from ventricular arrhythmic events (VT, VF and SCD) were all significantly higher in Responders compared to Non-responders (VT: 89.2% vs. 77.8% at 2 year, Log-rank p=0.031, VF: 99.2% vs. 89.9% at 2 year, Log-rank p=0.0031, SCD: 98.6% vs. 89.2% at 2 year, Log-rank p=0.0038) and event free survival rate from combined VT, VF and SCD was also significantly higher in Responders (87.8% vs. 76.5% at 2 year, Log-rank p=0.0013).

Conclusion: Response to CRT seems to reduce not only heart failure events, but also ventricular arrhythmic events.

Figure:

Adverse events in new onset AF vs no AF
Abstract 5925: Temporary Percutaneus Left Ventricular Stimulation in Patients with Cardiogenic Shock and Asynchronous Left Ventricular Contraction
Authors: Staab Charlotte , Piorkowski Christopher , Grebe Eik , Thiele Holger , Arya Arash , Sommer Philipp , Bode Kerstin , Hindricks Gerhard
Published: July 2021

Despite modern medical treatment strategies such as early coronary revascularization and intraaortic balloon pump cardiogenic shock is still associated with a high mortality. Cardiac resynchronization therapy (CRT) has shown significant benefits in patients with symptomatic heart failure and asynchronous left ventricular contraction. In the present study CRT was used as a temporary treatment strategy in patients with cardiogenic shock without further treatment options. 11 consecutive patients with cardiogenic shock (6 ICM, 5 DCM) and asynchronous left ventricular contraction (Δ PEP, SPWMD) received a temporary left ventricular (LV) lead, introduced through the right jugular vein and positioned in a posterolateral target vein. 4 patients were pacemaker dependent due to AV-block III, 7 patients were in SR with intrinsic AV conduction and additionally received a temporary right atrial lead for AV synchronous LV stimulation. The leads were externally connected to a re-sterilized single or dual chamber pacemaker. In all 11 patients the external LV lead could be positioned in a posterolateral target vein. Median procedure time was 24 (15;90) min. Median radiation time was 12 (8,25) min. After LV lead placement mean arterial pressure significantly improved in median by 15 (5,30) mmHg. After two days of therapy 8/11 (73%) patients were free from catecholamines. Median duration of temporary LV stimulation was 5 (2,12) days. The 30 day mortality measured 4/11 (36%). 6/7 surviving patients received permanent implantation of a CRT device subsequently. A temporary percutaneus left ventricular stimulation in patients with cardiogenic shock is feasible. In selected patients with terminal cardiogenic shock and lack of further treatment options temporary left ventricular stimulation can significantly improve the patient’s hemodynamic situation.
Abstract 5930: The Effect of Spironolactone on Myocardial Structure and Function Measured by Echocardiography in Patients with Early Stage Chronic Kidney Disease
Authors: Edwards Nicola C , Steeds Richard P , Ferro Charles J , Townend John N
Published: July 2021

Introduction
Early stage chronic kidney disease (CKD) is associated both with a high rate of adverse cardiovascular events and abnormal myocardial structure and function. Activation of the renin-angiotensin-aldosterone system is common in CKD and may result in adverse inflammatory, fibrotic and hypertrophic effects upon the heart and vasculature. Treatment with ACE inhibitors and ARBs frequently fails to suppress aldosterone production. We hypothesized that addition of the aldosterone antagonist spironolactone to ACE Inhibitors and ARB’s might reduce left ventricular (LV) mass and improve systolic and diastolic function measured by echocardiography.

Methods
One hundred and seventeen patients with stage 2 and 3 CKD, controlled hypertension (<130/85mmHg) and no history of cardiovascular disease or diabetes were recruited in to a double blind placebo controlled trial. After an active 4 week run in of spironolactone 25mg daily, patients were randomized to continue this treatment or receive placebo for a further 36 weeks. Echocardiographic assessment of LV mass, systolic and diastolic LV function was performed before run in and after 40 weeks of treatment.

Results
Compared to placebo, spironolactone reduced LV mass (mean (SD) −10g ± 10 vs.+3g ± 13, p<0.01). There was an improvement in LV Tei Index (−0.08 ± 0.1 vs. −0.001 ± 0.1, p<0.01) and mean basal long axis annular systolic velocities (Sm +1.4cm/s ± 1.9 vs. +0.1cm/s ± 1.1, p<0.01) but no difference in ejection fraction (+3% ± 5 vs.+2% ± 7). Transmitral E/A filing ratio (E/A +0.3 ± 0.3 vs −0.02 ± 0.2, p<0.05), basal annular early myocardial diastolic velocities (Ea +0.5cm/s ± 2.1 vs. −0.3cm/s ± 2.1, p<0.05), E/Ea ratio (−0.7 ± 1.9 vs. 0.1 ± 2.0, p<0.05), and colour flow propogation velocities (+8.7 ± 16.3 vs. −0.1 ± 16.6, p<0.05) were all improved. Systolic blood pressure was reduced with spironolactone but was not an independent predictor of change in any echocardiographic parameters.

Conclusion
Treatment with spironolactone reduced LV mass and improved both systolic and diastolic LV function. These data suggest that aldosterone plays an important role in cardiovascular disease in CKD and provides support for a clinical outcome trial investigating the use of aldosterone inhibitors to reduce cardiovascular risk.
Abstract 5934: Arrhythmogenic Right Ventricular Cardiomyopathy Due to Desmosomal Gene Mutations Is a Progressive Biventricular Disease
Authors: Basso Cristina , Carturan Elisa , Protonotarios Nikos , Bauce Barbara , Rampazzo Alessandra , Tsatsopoulou Adalena , Rizzo Stefania , Anastasakis Aris , Nava Andrea , Thiene Gaetano
Published: July 2021

Background:
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by a gradual loss of myocytes with fibro-fatty replacement. Mutations of gene encoding desmosomal proteins have been demonstrated in up to 50% of probands. The aim of this study was to assess the morphologic spectrum and the relative role of viruses on genotyped ARVC hearts.

Design:
Fourteen ARVC hearts (10 M/4 F, age range 7–64, mean 30 yrs), coming from sudden death (8), cardiac transplantation (4), heart failure (1) and extracardiac death (1) were investigated. Familial recurrence of ARVC was ascertained in 12 (86%). Genetic screening identified pathogenetic mutations in plakophilin-2 (5), desmoplakin (4), desmoglein-2 (2) and plakoglobin (3). Five hearts from patients with in ryanodine receptor 2 (Ryr2) gene mutations were also investigated. Morphopathologic investigation consisted of gross examination, histology, immunohistochemistry and molecular pathology (PCR) for cardiotropic viruses.

Result:
Cardiac involvement was biventricular in all but 1 case, a 7 year old girl who died of extracardiac causes and presented a structurally normal heart. Ventricular myocardium abnormalities consisted of fibro-fatty replacement in 12 cases and of subepicardial myocyte necrosis with acute inflammation and granulation tissue in a 15 year old boy who died suddenly. Inflammatory infiltrates were evident in 93% of cases, either diffuse (23%) or focal (77%), and mostly consisted of T-lymphocytes and macrophages. Molecular investigation was negative in all but one with Hepatitis C virus (7%). Ryr2 gene hearts showed only mild fatty infiltration confined to the antero-apical wall of the right ventricle.

Conclusion:
ARVC hearts from patients with desmosomal gene mutations are characterized by biventricular myocardial atrophy and fibro-fatty replacement. In early adolescence, the phenotype can be either absent or consistent with acute myocyte damage without fibro-fatty replacement, thus confirming the progressive nature of the disease. While myocarditis is a usual feature, viral genome is exceptionally detected in the myocardium as to support the reactive nature of inflammation. The pathologic features of Ryr2 hearts are not in keeping with ARVC.
Abstract 5949: Abnormal NT-Pro-BNP Levels in Asymptomatic Long Term Survivors of Childhood Cancer Treated with Anthracyclines
Authors: Mavinkurve-Groothuis Annelies M , Groot-Loonen Jacqueline , Bellersen Louise , Pourier Milanthy S , Feuth Ton , Bokkerink Jos P , Hoogerbrugge Peter M , Kapusta Livia
Published: July 2021

Objectives
:

to document plasma concentrations of cardiac Troponin T (cTnT) and NT-pro-brain natriuretic peptide (NT-pro-BNP) in a large group of asymptomatic long term survivors of childhood cancer treated with anthracyclines,

to study the relation of the abnormal biomarker levels with different risk factors for anthracycline-induced cardiotoxicity and conventional echocardiographic parameters.

Methods
: 122 asymptomatic survivors of childhood cancer underwent a detailed echocardiography. Blood samples were taken to determine the levels of NT-pro-BNP and cTnT.

Results
: None of the survivors had abnormal cTnT levels. The mean NT-pro-BNP level of our survivor group was 10 pmol/l (SD±9) with a range of 1–55 pmol/l. Thirteen percent of the survivors had abnormal NT-pro-BNP levels. Abnormal NT-pro-BNP levels were significantly related to cumulative anthracycline dosage (p<0.003). Eleven of 31 (35%) survivors treated with cumulative anthracycline dose of 300 mg/m
2
or more, had abnormal NT-pro-BNP levels which were significantly related to end-diastolic left ventricular internal diameter (LVIDd) indexed for body surface area (BSA) (p<0.01).

Conclusion
: Cardiac TnT does not contribute to the early detection of late onset anthracyline-induced cardiotoxicity. Abnormal levels of NT-pro-BNP were frequently detected in asymptomatic, long term survivors of childhood cancer. Follow up of these survivors, with both echocardiography and NT-pro-BNP, is essential to answer the question whether NT-pro-BNP is an early marker for late onset anthracycline-induced cardiotoxicity.
Abstract 5953: Flow Pulsation Affect Distal Pulmonary Artery Endothelial Cell mRNA Expression
Authors: Li Min , Stenmark Kurt , Shandas Robin , Tan Wei
Published: July 2021

Background:
Due to the development of pulmonary arterial hypertension (PAH), distal pulmonary artery endothelial cells (dPAEC) are exposed to wall shear stress (SS) that is different in physical characteristics compared to normal condition. The effect of individual components of SS on PAEC biology has not been thoroughly examined. Thus the current study was designed to examine how dPAEC respond to different component of SS in regarding to gene expression including adhesion molecules: ICAM, VCAM, E-selectin; chemokine: MCP-1 and growth factors:VEGF, Flt-1.

Methods:
Bovine dPAEC were cultured and placed on fibronectin-coated slides till confluent. Cells were then exposed to SS with different frequency (1Hz, 2Hz), pulsation (low, medium and high with an average SS of 14 dynes/cm
2
) and time (1hr or 6hrs). The flow studies were carried out using a flow chamber connected to a variable speed flow pump. All data was represented as fold change relative to static condition.

Results:
As shown in table

below,

The effect of flow frequency on gene expression depends on individual gene. There was no difference of ICAM expression between 1Hz and 2Hz. Frequency of 2Hz significantly increased VCAM and MCP-1 expression compared to frequency of 1Hz.

Compared to static condition, steady flow increased all gene expression. One hour pulsatile flow further increased ICAM, VCAM, E-selectin and MCP-1 but not VEGF or Flt-1 expression as pulsation increased. 3) Prolonged pulsatile flow further increased all gene expression.

Conclusion:
Physical characteristics of flow, especially flow pulsation stimulate dPAEC gene expression which can contribute to the development of PAH.
Abstract 5960: Implementation of Noninvasive Subharmonic Pressure Estimation on a Commercial Ultrasound Scanner
Authors: Leodore Lauren M , Leung Corina , Pelissier Laurent , Forsberg Flemming
Published: July 2021

This project aims to monitor and quantify intra-cardiac pressures via contrast-enhanced subharmonic imaging. We have proposed subharmonic aided pressure estimation (SHAPE; U.S. Patent 6,302,845) utilizing microbubble-based contrast agent signals for the noninvasive estimation of hydrostatic blood pressures in the heart cavities and in this study implemented real-time SHAPE on a commercial US scanner. An experimental pulse-echo system for SHAPE was constructed based on two single element transducers assembled confocally at a 60° angle to each other. A transducer with a bandwidth of 38% and a center frequency of 2.2 MHz (Staveley, East Hartford, CT) was used as the transmitter and a second transducer with a bandwidth of 86% and a center frequency of 3.6 MHz (Etalon Inc., Lebanon, IN) was the receiver. Changes in first, second, and subharmonic amplitudes of 6 different US contrast agents were measured in vitro at hydrostatic pressures from 0 –186 mmHg, acoustic pressures from 0.35– 0.60 MPa and frequencies of 2.5– 6.6 MHz. The optimal parameters for SHAPE were determined using linear regression analysis and implemented on a Sonix RP scanner (Ultrasonix Medical Corp, Richmond, Canada). The real-time implementation of SHAPE was tested in vitro. Over the pressure range studied the 1st and 2nd harmonic amplitudes reduced ~2 dB for all US contrast agents. Over the same pressure range, the subharmonic amplitudes decreased by 10 –14 dB and excellent linear regressions were achieved with the hydrostatic pressure variations (r
2
>0.98, p < 0.001). The optimal sensitivity for SHAPE was achieved at a transmit frequency of 2.5 MHz (i.e., receiving at 1.25 MHz) at a 0.35 MPa acoustic pressure using Sonazoid (GE Healthcare, Oslo, Norway) which declined ~14.4 dB in vitro. A Sonix RP scanner was modified to implement SHAPE on a phased array transducer PA4 –2 with a frequency range from 1.5– 4.5 MHz. A pulse inversion technique was used and the subharmonic signals are displayed in real-time and can also be stored for off-line analysis. SHAPE offers the possibility of allowing pressure gradients in the heart to be obtained noninvasively. Future studies will include in vivo pressure measurements. Supported by AHA grant no 06554414 and NIH HL081892.

This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).
Abstract 5961: Defining An Evidence-Based Cutpoint for Medication Adherence in Heart Failure
Authors: Wu Jia-Rong , Lennie Terry A , De Jong Marla J , Rayens Mary Kay , Chung Misook L , Riegel Barbara , Moser Debra K
Published: July 2021

Patients with heart failure (HF) are required to take multiple medications. Long-term adherence to the HF medication regimen is necessary in order to achieve better patient outcomes. Despite the importance of adherence, clinically relevant cutpoints for distinguishing the level of adherence associated with outcomes are unknown. The purpose of this study was to use outcomes (i.e., event-free) as a criterion to determine the level of medication adherence required to achieve the best clinical outcomes. The specific aim was to determine the cutpoint above which there is a positive relationship between level of medication adherence and outcomes. This was a longitudinal study of 135 patients with HF. Medication adherence was measured using a valid and objective measure, the Medication Event Monitoring System (MEMS). Two indicators of adherence were assessed by the MEMS:

dose-count, percentage of prescribed doses taken and

dose-days, percentage of days correct number of doses taken. Patients were followed up to 3.5 years to collect data on outcomes.

A series of Kaplan-Meier plots with log-rank tests, Cox-survival analyses, and receiver operating characteristic (ROC) curves were assessed comparing event-free survival in patients divided at one point incremental cutpoints. Event-free survival was significantly better when the prescribed number of doses taken [dose-count] or the correct dose [dose-day]) was ≥ 88%. This level was confirmed in a Cox regression model controlling for age, gender, ejection fraction, NYHA, comorbidity, angiotensin-converting enzyme inhibitor use, and beta-blocker use. ROC curves showed that adherence rates above 88 – 89% produced the optimal combination of sensitivity and specificity with respect to predicting better event-free survival. With this as the adherence cutpoint, patients in the nonadherent group were 2.2 times (by dose-count) to 3.2 times (by dose-day) more likely to experience a first event (
p
= .021 and .002, respectively), compared to patients in the adherent group. The results of this study provide clinicians and researchers with an evidence-based recommendation about the level of adherence needed to achieve the best outcomes.
Abstract 5986: Drug-Eluting Stent versus Bare Metal Stent Use: Meta-Analysis of Randomized Trials and Observational Studies
Authors: Kirtane Ajay J , Gupta Anuj , Iyengar Srinivas , Mehran Roxana , Moses Jeffrey W , Martin B , Applegate Robert , Hannan Edward , Harjai Kishore , Racz Michael , Jensen Lisette O , Park S. J , Perry Raphael , Saia Francesco , Simonton Chuck , Tu Jack V , Waksman Ron , Stone Gregg W
Published: July 2021

Background: The safety and efficacy of drug-eluting stents (DES) among more generalized patient populations than typically enrolled in pivotal randomized controlled trials (RCTs), including for “off-label” indications, is controversial. Objectives: We sought to perform a systematic review and meta-analysis of published/presented DES studies in order to estimate the relative impact of DES vs. BMS particularly outside of USFDA labeled indications, and to specifically assess differences between data derived from RCTs and observational (Obs) analyses.

Methods: Studies with >=100 total pts comparing DES to BMS and reporting mortality data with cumulative follow-up of >=1 year that were published and/or presented through 2/2008 were abstracted. Fixed effects and random effects models were used to generate summary estimates of the relative impact of DES vs. BMS upon all-cause mortality, myocardial infarction (MI), and target vessel revascularization (TVR). Data from 9,470 pts enrolled in 22 RCTs and from 182,901 pts studied in 34 Obs studies were included; RCT and Obs data were analyzed separately.

Results: Data from “off-label” RCTs demonstrated non-significant reductions in mortality with DES vs. BMS, with a significant reduction in TVR (Table

). The Obs studies (in which pts were treated for both on-label and off-label indications) demonstrated significant reductions in mortality and TVR with DES vs. BMS use (Table

).

Conclusions: Use of DES compared to BMS does not appear to be associated with adverse safety outcomes such as death or MI in either off-label RCTs or non-randomized Obs studies, and was associated with a significant and comparable reduction in TVR. In the absence of definitive large-scale randomized data directly comparing DES to BMS in unselected pts, these findings, derived from more than 190,000 total pts treated in 56 studies, suggest that DES are safe and have comparable efficacy in both RCTs and in the “real-world”.
Abstract 5987: Long-Term Efficacy and Safety of Sirolimus-Eluting Versus Bare-Metal Stents for On- and Off-Label Indications
Authors: Dada Marcin R , Kiernan Francis J , Murphy Deborah J , Cloutier Jill , Kapetanopoulos Athanasios , Singh Bhupinder , Sayyed Rameez , Mather Jeffrey F , Mennett Roger A , Shah Anuj R , McKay Raymond G
Published: July 2021

BACKGROUND:
Although previous data suggest persistent clinical benefit of sirolimus-eluting stents (SES) in reducing target vessel revascularization without an increase in myocardial infarction (MI), cumulative stent thrombosis and mortality, the long-term safety and efficacy of CYPHER stent use in routine clinical practice, including off-label stent implantation, remains uncertain.

METHODS:
We examined clinical characteristics, angiographic findings, in hospital and long-term clinical outcomes in 3572 patients of whom 2,550 were treated with SES, and 1,022 who were treated with bare metal or heparin-coated stents (BMS). The study groups included 1,058 SES patients (41.5%) and 488 BMS patients (47.7%) with off-label indications, including acute MI, multivessel percutaneous coronary intervention, saphenous vein grafts and complex lesion morphology. A propensity-score method was utilized to adjust for differences in baseline characteristics. Patients were followed for up to 5 years for the occurrence of all-cause mortality, MI and repeat target vessel revascularization.

RESULTS:
Compared to the BMS patients, the SES group patients demonstrated significantly improved event-free survival with respect to all-cause mortality (RR, 1.39; 95% CI, 1.07 to 1.80, p=0.014) and repeat target vessel revascularization (RR, 2.72; 95% CI, 1.99 to 3.73, p<0.001) during the follow-up period, with no significant difference in the incidence of MI. A landmark analysis, examining composite adverse events occurring six months after stent implantation in the two study groups, demonstrated no increased late hazard associated with SES use (relative risk, 1.08; 95% CI, 0.80 to 1.46).

CONCLUSIONS
: Use of SES in routine clinical practice, including off-label indications, is associated with improved long-term mortality, reduced need for repeat target vessel revascularization and no increase in MI compared to BMS.
Abstract 6001: Two Years Clinical Registry Follow Up of Endothelial Progenitor Cell Capture Stent versus Sirolimus-Eluting Bioabsorbable Polymer-Coated Stent versus Bare Metal Stents in Patients Undergoing Primary Percutaneous Coronary Intervention for ST Elevation Myocardial Infarction
Authors: Chong Eric , Shen Liang , Soon Chao Y , Ong Hean Y , Poh Kian K , Teo Swee G , Lee Ronald C , Low Adrian , Tan Huay C
Published: July 2021

Background:
Endothelial progenitor cell (EPC) capture stent (Genous
™
, OrbusNeich), is designed to promote rapid endothelization and healing and is potentially useful in patients undergoing primary percutaneous coronary intervention (PPCI) for acute ST-segment elevation myocardial infarction (STEMI). We compare its clinical efficacy and safety with a sirolimus-eluting (SES) bioabsorbable polymer-coated stent (Cura
™
, OrbusNeich) and a bare metal stent (BMS) (Liberte
™
, Boston scientific) in patients presenting with STEMI.

Methods:
All patients presented to our center with STEMI and received PPCI with either EPC, SES or BMS stents between Jan 2004 and June 2006 were enrolled in the cohort study. The study endpoints were major adverse cardiac events (MACE) defined as composite end point of death, myocardial infarction (MI) and target vessel revascularization (TVR) at 2 years as well as acute, subacute and late stent thrombosis.

Results:
A total of 366 patients (EPC=95, SES=53, BMS 218) were enrolled. Baseline demographics in terms of age, gender, diabetes mellitus, baseline renal impairment, pre-discharge left ventricular ejection fraction, cardiogenic shock were comparable among the 3 groups. Procedural success rate was high at a mean of 99.5%. Post-procedural TIMI 3 flow was achieved in EPC 91.6%, SES 96.2% and BMS 88.5%. The MACE and stent thrombosis results at 2 years are shown in the table

.

Conclusion:
The MACE rates among patients who underwent PPCI were similar in all 3 stent groups at 2 years follow-up. There was no difference in TVR rate and stent thrombosis remains a low event occurrence. None of the patients in the EPC stent group developed late stent thrombosis at 2 years follow up.
Abstract 6019: The Impact of Blood Transfusion and Other Bleeding Measures on Subsequent Mortality Among Patients Undergoing Primary PCI for Acute Myocardial Infarction: The HORIZONS-AMI Trial
Authors: Kirtane Ajay J , Parise Roxana Mehran Helen , Witzenbichler Bernard , Guagliumi Giulio , Peruga Jan Z , Brodie Bruce , Dudek Dariusz , Pocock Stuart , Clayton Tim C , Tourkova Vilia , Dangas George D , Lansky Alexandra J , Stone Gregg W
Published: July 2021

Background: Bleeding complications are strongly associated with subsequent mortality among pts with ACS. The relative importance of the individual components of the composite bleeding scales used in clinical trials is poorly understood.

Objectives and Methods: Data were drawn from the HORIZONS-AMI, in which 3602 pts with STEMI undergoing primary PCI were randomized to treatment with heparin plus a glycoprotein IIb/IIIa inhibitor vs. bivalirudin alone. Bleeding and mortality outcomes were independently adjudicated using the ACUITY major bleeding scale, which incorporates laboratory data, clinical bleeding measures including blood transfusions and access site hematomas, and other parameters. The relative impacts of various bleeding components upon 30 day mortality were examined using multivariable modeling with individual components of the ACUITY bleeding scale incorporated as time-updated covariates.

Results: By 30 days, 238 pts experienced a non CABG major bleeding event (6.6%), and 93 patients died, 26 of whom (28.0%) had a prior major bleed. Bleeding was independently associated with subsequent mortality (adjusted HR 4.29 [2.57, 7.17]). Of the individual components of the ACUITY scale (each modeled independently), retroperitoneal bleeding, reoperation for bleeding, receipt of a blood transfusion, and a reduction in hemoglobin concentration >=4 g/dL were all associated with subsequent mortality after controlling for baseline characteristics and randomized treatment assignment (Table

).

Conclusions: Objective assessment of the impact of specific components of bleeding scales upon subsequent mortality is possible, and suggests differing relative impacts of these components. A significant proportion of attributable deaths are related to a reduction in hemoglobin >=4 gm/dL and/or receipt of a blood transfusion.
Abstract 6025: Optimal Stent Deployment. Five Seconds Is Not Enough
Authors: Hovasse Thomas , Lefèvre Thierry , Ohanessian Alice , Sastry Sanjay , Bande Marta , Bendaoud Nabil , Louvard Yves , Morice Marie-Claude
Published: July 2021

Background
. The risk of thrombosis which had been well described since the advent of stenting, is currently being re-addressed in the era of drug-eluting stents (DES). Among the predictors of thrombosis risk, there are some factors which may be favourably influenced by the operator. Indeed, the quality of stent deployment is crucial, which has been well demonstrated with IVUS. Inadequate deployment may be associated with numerous parameters. The time factor has never been explored accurately so far.

Objectives.
The purpose of this study was to analyse the relationship between the duration of stent balloon inflation and the quality of stent deployment as measured by StentBoost
™
in patients with de novo lesions.

Methods.
StentBoost
™
is a software developed by Philips on the flat panel detector, which averages frames, correcting for motion by using the balloon markers. This creates an enhanced image of the stent with an improved signal-to-noise ratio and allows precise measurements. Pressure of stent deployment was selected according to the reference diameter of the lesion and the diameter/pressure chart of the stent delivery system. A constant pressure was applied for 25 seconds and stent size measured at 5, 15, 25 sec., after deflation and post dilatation when performed. Primary endpoint was optimal stent expansion defined as minimal stent diameter/reference diameter at the lesion site > 80%.

Results.
Data were collected prospectively in 77 patients aged 67.8± 12.4 yrs, diabetic (38%), acute coronary syndrome (37 %), in whom 109 stents (length 18.7±6.4 mm; diameter 2.96±0.49 mm) were deployed at a mean pressure of 13.5±2.48 atm. Lesion reference diameter was 3.06±0.58 mm.

Conclusion.
Better stent implantation may be achieved by increasing the duration of stent deployment. This may influence the risk of stent thrombosis.
Abstract 6057: Elevated LDL-Cholesterol Causes a Higher Exercise Blood Pressure Response
Authors: Duprez Daniel A , Florea Natalia , Xu Jia , Grandits Gregory A , Hoke Lynn , Cohn Jay N
Published: July 2021

Background: Increased blood pressure (BP) response during exercise has been associated with an increased cardiovascular risk. It is unknown how LDL-cholesterol (LDL-c) is related to the exercise-induced BP response as well as to the large (LAE) and small artery (SAE) elasticity in subjects free from overt cardiovascular disease (CVD). We examined the relationship between serum LDL-c and the BP response during a moderate exercise treadmill test in subjects with no overt CVD and also the relationship between LDL-c and LAE and SAE.

Methods: 1229 Subjects (700 male, 529 female) free of overt CVD were recruited during a CVD prevention screening program. A fasting venous blood sample was taken for LDL-cholesterol determination. LAE and SAE were derived from radial pulse wave contour analysis. Resting BP was measured. Then they performed a treadmill exercise test for 3 minutes at a 5 METS (metabolic equivalents) workload. Systolic and diastolic BP were measured at the peak of the 3 min exercise test, The study population was divided in quartiles among distribution of LDL-cholesterol (LDL-c).

Results: Table 1

summarizes the results. There was no significant difference in large artery elasticity.

Conclusions: In asymptomatic subjects, LDL-c is not related with resting BP. Higher LDL-c is related with higher exercise systolic BP response. This higher BP response can be explained by a lower smaller artery elasticity which is a marker for endothelial dysfunction probably related to higher LDL-c. Further studies to examine the effect of lipid-lowering therapy on exercise BP response are warranted

Table 1