bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 1641: Attenuation-correction Does Not Improve Quantitative Diagnostic Performance of Myocardial Perfusion SPECT in Women
Authors: Wolak Arik , Slomka Piotr J , Fish Mathews B , Gerlach James , Lorenzo Santiago , Berman Daniel S , Germano Guido
Published: July 2021

BACKGROUND: Attenuation Correction (AC) for myocardial perfusion single photon emission computed tomography (MPS) had not been evaluated separately in female population despite specific considerations in this group due to breast photon attenuation. We aimed to compare the performance of AC in women using automated quantitative analysis of MPS.

METHODS: Consecutive female pts, 137 low likelihood (LLk) and 115 with coronary angiography performed within < 3 months of MPS, referred for rest/stress ECG gated Tc-99m sestamibi MPS with AC (Vantage Pro, Philips), were considered. Imaging data were evaluated for contour quality control (QC). Additional 50 female LLk studies were used to create equivalent normal limits for studies with AC and with no correction (NC). An experienced technologist (JG) blinded to the angiography and other results performed contour QC. All other processing was performed in a fully automated manner. Quantitative analysis was performed using Cedars Cardiac Suite version 2005, (QPS). All automatic segmental analysis was performed in 17-segment/5 point AHA model. Summed Stress Scores (SSS) ≥ 4 were considered abnormal. Receiver Operator Characteristics (ROC) areas-under- curve (AUC) were obtained by Analyze-It (v 1.171) statistical package.

RESULTS: CAD (≥ 70% stenosis) was present in 70/115 (61%) pts. The normalcy rates were 96% and 98% for studies with and without AC, respectively (P=NS). SSS in studies with or without AC were the same with the exception of normal patients were SSS was higher for studies with AC. The diagnostic performance of MPS with and without AC for detection of CAD is summarized in the table

.

Conclusions: There are no diagnostic differences between quantitative MPS analysis with or without AC in women and no gain in specificity or normalcy rates contrary to previously reported findings in general populations.
Abstract 1642: Head-to-Head Comparison of Myocardial Perfusion SPECT Imaging and Delayed Enhancement Magnetic Resonance Imaging to Detect Myocardial Infarction
Authors: Carlsson Marcus , Arheden Hakan
Published: July 2021

PURPOSE: Direct visualization of myocardial infarction is possible by delayed enhancement MRI (DE-MRI). The method has been validated in animal studies and patients and is considered to be the reference method for infarct assessment. However, myocardial perfusion SPECT has remained the most common method to depict stress induced ischemia and gives simultaneous information on myocardial infarction. The accuracy of gated SPECT for infarction assessment has been under debate stating that SPECT has limited sensitivity. Therefore, the aim of this study was to determine the sensitivity and specificity of gated SPECT for infarct assessment using MRI as reference method.

METHODS: 96 patients (32 females) referred for myocardial perfusion SPECT imaging were included. A body weight adjusted dose of technetium labelled tetrofosmin was injected at rest and during adenosine infusion and gated SPECT images were aquired in all but 2 patients where SPECT were acquired without ECG-gating. In all patients, DE-MRI were performed the same day. All images were evaluated visually with the observers blinded to all clinical data and to the results of the other imaging study.

RESULTS: In 29 patients infarcts were visualized by MRI. Of these, 25 patients had infarct detected by gated SPECT. Thus, the sensitivity and specificity for infarct detection by gated SPECT on patient basis were 86% and 97%, respectively.

CONCLUSION:. This study has showed high sensitivity and very high specificity for gated SPECT on a patient basis for infarct detection. Thus, gated SPECT can be used for infarct detection with good accuracy in patients with suspected ischemic heart disease.
Abstract 1652: Age Adjusted Modification of the Duke Treadmill Score Nomogram
Authors: Rafie Amir H Sadrzadeh , Sungar Gannon W , Myers Jonathan , Froelicher Victor F
Published: July 2021

Background

: The Duke Treadmill Score (DTS) is an established clinical tool for risk stratification of patients referred for routine exercise testing, but it does not consider age. Our objectives were to determine if age could improve the prognostic power of the DTS and if so, to modify the DTS nomogram to include age.

Methods and Results

: Analyses were performed on 1959 patients referred for exercise testing at the Palo Alto Veterans Affairs Medical Center from 1997 to 2004. After removal of female and heart failure patients, 1759 male veterans (age range: 23 to 86 years) remained. The DTS was calculated as follows: [(exercise time) − (5 × maximum ST-segment deviation) − (4 × treadmill angina index)]. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves were plotted. Cox survival analysis was performed entering age and the DTS. Age and the DTS had similar magnitude but opposite signs yielding the following score: [Age − DTS]. The new score yielded an area under the ROC curve of 0.80 compared to 0.76 for the DTS. Using this equation, a nomogram was constructed by adding age to the original DTS nomogram. The point at which Age-DTS line intersects the drawing line from the DTS to the corresponding value for age indicates average annual cardiovascular mortality adjusted for age.

Conclusions

: We propose an age adjusted DTS nomogram that improves the prognostic estimates of average annual cardiovascular mortality over the DTS alone. This nomogram requires external validation and extension to women.
Abstract 274: Physical Coupling Supports Local Ca2+ Coupling Between SR Subdomains and the Mitochondria in Heart Muscle
Authors: Garcia-Perez Cecilia , Hajnoczky Gyorgy , Csordas Gyorgy
Published: July 2021

Propagation of ryanodine receptor (RyR) dependent SR Ca2+ release to the mitochondria is locally supported by high [Ca2+] microdomains at close contacts between the organelles. The objective of this study was to clarify if the close associations of SR and mitochondria underlying the local Ca2+ communication were secured via a physical coupling. Crude and Percoll-purified mitochondrial fractions of rat heart homogenates were tested for the presence of mitochondria-associated SR fragments capable of RyR-dependent Ca2+ mobilization and Ca2+ delivery to the mitochondria. SR and mitochondrial marker proteins were analyzed by Western blot or visualized in situ by immunofluorescent labeling and imaged using confocal microscopy. Mitochondrial matrix [Ca2+] ([Ca2+]m) was monitored using fluorescence imaging of rhod-2-loaded adherent individual vesicles. Ample presence of SR markers (calsequestrin, SERCA2a, phospholamban) was detected in the crude mitochondria, whereas after percoll purification they were barely detectable in the ‘heavy’ fraction but remained present in the ‘light’ fraction. ‘Immunomitochemistry’ revealed various sizes of SR particles in the crude fraction, a large portion of which was colocalized with mitochondria, while showed less SR markers in the percoll-purified heavy fraction. Fluorescence Ca2+ imaging in the adherent particles revealed well-detectable [Ca2+]m responses to caffeine stimulation that was prevented by Ca2+ predepletion of the SR using the SERCA inhibitor thapsigargin (Tg), or by inhibitors of mitochondrial Ca2+ uptake. Because the Ca2+ released from SR was diluted in the large volume of the incubation medium without causing a change in the bulk [Ca2+], only local Ca2+ regulation could mediate the Ca2+ transfer to the mitochondria. Despite the hardly detectable presence of SR, the percoll-purified ‘heavy’ mitochondrial fraction still displayed a caffeine-induced [Ca2+]m rise that was abolished by Tg-pretreatment. Our data suggest that the SR-mitochondrial associations where the local Ca2+ coupling is established, are supported by physical links between the two organelles and the mitochondria bound SR surface represents a relatively small fraction of the total SR.
Abstract 276: Heme Oxygenase-1 Induction Modulates Hypoxic Pulmonary Vasoconstriction
Authors: Ahmad Mansoor , Abraham Nader G , Wolin Michael S
Published: July 2021

Endothelium removed Bovine pulmonary arteries (BPA) contract to hypoxia through a mechanism potentially involving lowering of superoxide-derived hydrogen peroxide and removing its basal relaxing effect. Induction of heme oxygenase-1 (HO-1) in BPA by 24 hr organ culture with 0.1mM cobalt chloride was accompanied by a decrease in 5μM lucigenin-detectable superoxide and an increase in horseradish peroxidase-luminol detectable peroxide levels. Force development to 20mM KCl in BPA was not affected by HO-1, but hypoxic pulmonary vasoconstriction (HPV) was significantly reduced. Organ culture with a HO-1 inhibitor (10μM chromium mesoporphyrin) reversed the effects of HO-1 on HPV and peroxide. Pretreatment of BPA with a copper chelator 10mM diethyldithiocarbamate (DETCA) to inactivate Cu,Zn-SOD, prevented the conversion of superoxide to peroxide, and attenuated HPV. DETCA treatment increased superoxide and decreased peroxide to similar levels in control and HO-1 induced BPA. Peroxide scavenging with 0.1mM ebselen increased force development to 20mM KCl and partially reversed the decrease in HPV seen on induction of HO-1. Thus HO-1 induction in BPA causes an increase in superoxide scavenging by Cu,Zn-SOD resulting in increased levels of peroxide, leading to an attenuation of HPV. The generation of superoxide in BPA is not affected by HO-1 induction as DETCA treated control and HO-1 BPA show similar levels of superoxide. Thus, HO-1 induction appears to attenuate HPV in BPA by increasing the conversion of superoxide to peroxide, leading to peroxide levels which may not be adequately lowered by hypoxia.
Abstract 1675: Effect of Rosiglitazone versus Placebo on Rapid Angiographic Progression of Non-Culprit Coronary Lesions in Patients with Type 2 DM
Authors: Finn Aloke , Oh Jae S , Hendricks Michael , Daher Maureen , Nadelson Jeffrey , Crimins Johanna , Kastrati Adnan , Schomig Albert , Bruskina Olga , Palacios Igor , John Michael C , Gold Herman K
Published: July 2021

Background: We examined the effect of 4mg/day rosiglitazone (RSG) versus placebo (PLC) on rapid angiographic progression (RAP) of non-culprit coronary lesions (NCCL) in type 2 diabetes (DM 2).

Methods: Using biomarkers and angiograms from 43 DM 2 enrolled in a randomized controlled double blind trial examining the effects of RSG or PLC on late loss after PCI, we investigated the effects of RSG on RAP of NCCL using logistic regression. All stenoses >=30% of vessel diameter were identified at baseline and quantified by QCA. Patients had 8 month angiography and biomarkers (HOMA (insulin resistance index), insulin, MMP-9, adiponectin (ADI), fibrinogen, hs-CRP, A1C, and LDL and HDL cholesterol) drawn at baseline and 4 months. RAP was defined as >=20% diameter reduction of pre-existing NCCL by QCA, or a new narrowing >=30% arising in a segment angiographically normal at baseline.

Results: There were 52 NCCL in the RSG versus 56 in the PLC. 14.8 % (16/108) of lesions had RAP with 7/52 (13.5%) lesions progressing in RSG versus 9/56 (16.1%) in PLC, p=ns. RSG was not a predictor of RAP. Of the biomarkers and angiographic variables examined, hsCRP was the only predictor of RAP. Patients with a 120 day hsCRP above the 75th percent had an OR of 7.35 [2.35,23] for RAP versus those below. Interestingly, although RSG treatment lowered hsCRP at 4 months (RSG 2.03Â±2.8 mg/dl vs. Placebo 3.37Â±4.25, p=0.06), it did not decrease the likelihood of plaque progression in either the low or high hsCRP groups (see graph). LDL levels at this time were not different (RSG 74Â±23 mg/dl vs. PLC 89Â±32, p=ns).

Conclusion: 120 day hsCRP is a predictor of RAP. Despite lowering 120d hsCRP, RSG did not lower the frequency of RAP.
Abstract 1684: Invasive Assessment of the Coronary Microcirculation: Novel Thermodilution Based Measure of Absolute Microvascular Resistance
Authors: Ho Yen-Dong , Nguyen Tom C , Itoh Akinobu , Yeung Alan C , Fearon William F
Published: July 2021

Background:
Assessment of coronary microcirculatory function would aid in understanding the pathophysiology of various disease states. Recently Pijls and colleagues introduced a novel thermodilution based measure of absolute coronary flow. We hypothesize that this method will allow quantitation of absolute microvascular resistance during cardiac catheterization.

Method:
Using a coronary pressure/temperature wire and subselective coronary infusion catheter, volumetric coronary flow (Q) is derived by principle of thermodilution from saline infusion rate (Q
k
), saline temperature (T
k
) at infusion catheter tip relative to baseline blood temperature, and distal blood temperature (T) relative to baseline blood temperature, with Q = Q
k
· (T
k
/T) · 1.08. We hypothesize that distal coronary pressure divided by calculated flow provides a measure of microvascular resistance (MR) and will correlate with true microvascular resistance (TMR), defined as distal coronary pressure divided by hyperemic flow measured with external ultrasonic flow probe. A total of 111 measurements in the left anterior descending (LAD) distribution were made in 8 Yorkshire swine at baseline and after microcirculatory disruption with microsphere embolization, with and without epicardial LAD stenosis.

Results:
Thermodilution based LAD flow correlated well with ultrasound based flow (
r
= 0.88, p < 0.0001, mean absolute difference 20 ml/min), in both presence (
r
= 0.88, p < 0.0001) and absence (
r
= 0.87, p < 0.0001) of microcirculatory disruption. Correspondingly, there was significant agreement between MR and TMR (
r
= 0.66, p < 0.0001). Mean MR increased significantly after microsphere injection (0.54 ± 0.11 to 0.86 ± 0.18 mmHg · mL
−1
· min
−1
, p < 0.0001), in both presence (0.56 ± 0.12 to 0.82 ± 0.11 mmHg · mL
−1
· min
−1
, p < 0.0001) and absence (0.49 ± 0.06 to 0.91 ± 0.27 mmHg · mL
−1
· min
−1
, p < 0.0001) of epicardial stenosis. After microcirculatory disruption, % change in MR (164 ± 30%) was similar to % change in TMR (161 ± 36%, p = NS
vs.
MR % change).

Conclusion:
This novel thermodilution based method provides quantitative and accurate assessment of microvascular resistance in selective coronary territories and can facilitate investigation of coronary physiology during cardiac catheterization.
Abstract 1706: Elevation of Pericardial Fluid Active Matrix Metalloproteinase-9 (MMP-9) Level Is Closely Associated With Left Ventricular Remodeling
Authors: Miyamoto Shoichi , Inoko Moriaki , Nagai Kunihiko , Nakane Eisaku , Abe Tomomi , Sasaki Kenichi , Nakashima Junji , Tanaka Nozomi , Uehara Kyokun , Ueyama Koji , Hosokawa Ryohei , Nohara Ryuji , Fujita Masatoshi
Published: July 2021

Background: The development of congestive heart failure (CHF) is associated with left ventricular (LV) remodeling. However, fundamental mechanisms that contribute to this remodeling process remain unclear. The matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) have been demonstrated to play a significant role in tissue remodeling through a number of pathological processes.

Objectives: The purpose of this study was to investigate whether MMPs and TIMPs represent autocrine/paracrine factors and are accumulated in pericardial fluid. We previously reported that active MMP-2 levels in pericardial fluid served as more sensitive and accurate indicators of LV remodeling than did active MMP-2 levels in plasma.

Methods: We measured the concentrations of the enzyme (active MMP-9) in both plasma and pericardial fluid in 20 patients during coronary artery bypass graft surgery.

Results: The active MMP-9 level was significantly higher in pericardial fluid than in plasma (4.68 ± 1.17 vs. 2.58 ± 0.29 ng/ml, p<0.0001). Interestingly, the pericardial fluid levels of active MMP-9 were significantly higher in patients with impaired LV function than in those with normal LV function (5.25 ± 0.57 vs. 2.96 ± 0.65 ng/ml, p<0.0001). Pericardial fluid active MMP-9 levels had closer relations with LVEDVI (r=0.459, p=0.047) and LVESVI (r=0.490, p=0.0321) than did plasma active MMP-9 levels (LVEDVI: r=0.065, p=NS; LVESVI: r=0.254, p=NS). Active MMP-9 levels in pericardial fluid but not in plasma inversely correlated with LV ejection fraction (r=−0.626, p=0.0033).

Conclusions: Active MMP-9 levels in pericardial fluid serve as more sensitive and accurate indicators of LV remodeling than did active MMP-9 levels in plasma. Thus, active form of MMP-9 may be also secreted from the heart into the pericardial space with the progression of CHF, and it may have a pathophysiologic role in LV remodeling process as an autocrine/paracrine factor.
Abstract 1736: Is There An Indication For Transcoronary Ethanol VT Ablation In 2007?
Authors: Sacher Frederic , Sobieszcyk Piotr , Tedrow Usha , Einsenhower Andrew , Seldwyn Andrew , Raymond Jean-Marc , Koplan Bruce , Epstein Laurence , Stevenson William
Published: July 2021

Introduction: TransCoronary Ethanol Ablation (TCEA) was proposed 15 years ago for incessant VTs resistant to any treatment (medications or ablation). However we sought to investigate whether this therapy could still be useful in the area of modern radiofrequency ablation.

Methods: Eight patients (6 males, 55 ±7yo, 2.1 ±0.8 failed VT ablations) out of 586 VT ablation procedures underwent TCEA between 2000 and 2006. After identification of the artery supplying blood to the arrhythmogenic area, an angioplasty balloon was advanced in the artery then VT was induced and cooled saline infusion was performed distal to the balloon. If this did not interrupt VT another artery was targeted. If VT stopped, 1 to 5 ml of pure ethanol (96%) was injected.

Results: All patients had scar related VT (septal:7, left inferior wall:1) with 4 pts having a non ischemic cardiomyopathy. Mean left ventricle ejection fraction prior to the procedure was 23 ±9%. In patients with septal scar, 1st and/or 2nd septal artery were targeted in 5 pts whereas for 2 this was not effective and a distal branch of the circumflex and the conus branch of the right coronary artery were targeted in 2. A branch of the posterior descending artery was targeted in the patient with inferior scar. Acute success was obtained in 5/8 (63%). Two patients experienced complications (transient cardiac stunning after ethanol infusion and delayed AV block). Twenty-four hours after the procedure, mean troponin Ic [0 – 0.1 ng/ml] and CPK-MB [0–5 ng/ml] were respectively 19.75 ±12.79 ng/ml and 121 ±108 ng/ml, mean ejection fraction was 18 ±8%(NS compared to before). With a mean follow-up of 29 ±23 months, 6/8 (75%) patients are still alive with no recurrence in 4 (50%).

Conclusion: TCEA is an option in cases of refractory VT who fail radiofrequency ablation, especially in cases of septal scar.
Abstract 1742: Expression of the Anti-Angiogenic Proteins Angiostatin and Endostatin is Increased in Diabetic Patients and Associated with Impaired Coronary Collateral Formation
Authors: Sodha Neel R , Boodhwani Munir , Clements Richard T , Xu Shu-Hua , Laham Roger L , Sellke Frank W
Published: July 2021

Introduction:
Coronary artery disease is the leading cause of mortality in diabetics. Due to the diffuse nature of their disease, diabetics may be at risk for incomplete revascularization, highlighting a potential role for pro-angiogenic therapy in this group. This study investigates molecular mechanisms of angiogenesis in diabetics.

Methods:
Myocardial tissue was harvested from patients undergoing CABG (non-diabetic (ND) 11, type 2 diabetic (DM) 10). Expression of angiostatin, endostatin, their precursors (plasminogen and collagen XVIII, respectively), enzymes leading to their production (Matrix Metalloprotease (MMP) 2 & 9), and an inhibitor of MMPs (TIMP2) was assessed with western blotting. MMP activity was assessed. Serum levels of angiostatin and endostatin were assayed. Coronary collateralization was graded by Rentrop scoring of angiograms.

Results:
Plasminogen and collagen XVIII expression were similar between groups. Angiostatin expression trended to increase 1.24-fold (p=0.07) and endostatin expression increased 2.02-fold in DM patients relative to ND (p=0.02). Serum angiostatin was 2.68-fold higher (p=0.03) and endostatin 1.39-fold higher (p=0.04) in diabetics. MMP9 expression was no different between groups, whereas MMP2 expression decreased 1.8-fold in diabetics (p=0.003). MMP2 & 9 activity decreased 1.33-fold (p=0.03) and 1.57-fold (p=0.04), respectively, in diabetics. Coronary collateralization scores were ND 2.1 ± 0.37 vs. DM 1.0 ± 0.4 (p=0.05). Myocardial endostatin expression correlated strongly with %HbA1c (R=0.742, p=0.0001). Myocardial expression of angiostatin and endostatin demonstrated significant negative linear correlations with coronary collateralization (angiostatin R=−0.531, p=0.035, endostatin R=−0.794, p=0.0002).

Conclusion:
Diabetics exhibit increased levels of the anti-angiogenic proteins angiostatin and endostatin and differential regulation of the enzymes governing their production relative to non-diabetics. Myocardial levels of these proteins show significant correlation to coronary collateralization. These findings offer potential new therapeutic targets for enhancing pro-angiogenic therapy and insight in to the angiogenic impairments seen in diabetes.
Abstract 1743: Identification of a Novel Susceptibility Locus at 9q21 for Familial Bicuspid Aortic Valve Disease
Authors: McKellar Stephen H , Yagubyan Marineh , Majumdar Ramanath , Tester David J , de Andrade Mariza , Garg Vidu , Ackerman Michael J , Sundt Thoralf M
Published: July 2021

Background:
Bicuspid aortic valve disease (BAV), the most common congenital cardiovascular malformation, has an incidence of 0.5–1.0% of live births. While most cases of BAV appear to be sporadic, familial inheritance patterns have been observed consistent with autosomal dominant inheritance with variable penetrance. However, little is known about specific genetic loci responsible for familial BAV. Here, we performed linkage analysis on a large multi-generational pedigree affected with BAV.

Methods:
We identified a large, five-generation pedigree (136 family members) with 10 individuals having BAV. Two-dimensional echocardiography was used to assign aortic valve phenotype. Genome-wide linkage analysis using 430 microsatellite markers (Marshfield Clinic) and fine mapping using 100 single nucleotide polymorphisms (Affymetrix) on chromosome 9 was performed on genomic DNA from all available family members. Logarithm of odds (LOD) scores of >2.0 were considered suggestive of linkage. Comprehensive splice site/open reading frame mutational analysis of candidate genes residing in the putative locus is underway using PCR, DHPLC, and DNA sequencing. A candidate gene,
KLF9,
Krüppel-like factor 9 was analyzed for mutations because of its role in cardiogenesis.

Results:
Multi-point genome-wide linkage analysis demonstrated a 7 cM region on chromosome 9q21 that was suggestive of linkage for familial BAV with a maximum multipoint LOD score of 2.8 flanked by the microsatellite markers GATA7D12 and D9S1834. This region contains several candidate genes with biological plausibility for BAV phenotype.
KLF9-
encoded Krüppel-like factor 9, localized to chromosome 9q21, was targeted as a prime candidate gene for familial BAV. However, no mutations involving the translated exons of
KLF9
were detected. Further fine mapping studies and candidate gene analysis are currently underway.

Conclusions:
We report a novel susceptibility locus on chromosome 9q21 for BAV in a large multi-generational family. Although coding region mutations in
KLF9
are not responsible for BAV in this pedigree, several candidate genes with biological plausibility for the development of congenital BAV lie within this region and warrant further scrutiny.
Abstract 1781: Nonprotected Left Main Stenosis: Multicenter Randomized Trial Between Total Arterial Revascularization and Interventional Treatment
Authors: Boudriot Enno , Schuler Gerhard , Walther Thomas , Falk Volkmar , Liebetrau Christoph , Thiele Holger , Boeckstegers Peter , Reichart Bruno , Pohl Tilman , Mudra Harald , Kempkes Bernhard , Beier Florian , Neumann Franz-Joseph , Eschenbruch Elmar , Gick Michael , Krozingen Herzzentrum Bad , Mohr Friedrich W
Published: July 2021

Background:
Nonprotected left main coronary stenosis is still considered an indication for bypass surgery. We conducted a multicenter prospective randomized trial to compare total arterial revascularization (CABG) with interventional treatment (PCI) in these patients.

Methods and Demographics:
Between 8/2003 and 5/2007 a total of 156 pts with significant stenosis of the nonprotected left main coronary artery were recruited for the study. We report the first 111 pts whith one year follow up. They were randomized to undergo CABG or PCI using drug eluting stents (Sirolimus). Additional lesions in other locations were treated concurrently. Angiographic control was performed at 12 months. Primary endpoints were death, acute myocardial infarction and re-intervention at 12 months. Out of the 111 pts 55 pts were randomized for CABG and 56 for PCI. Mean age was 65 ± 7 years, diabetes was present in 35%. There were no significant differences between both groups with respect to other baseline variables. The lesion was located at the ostium in 17%, midshaft in 11%, and distally in 72%. An average of 2.4 ± 1.1 stents were implanted, and 2.4 ± 0.6 bypass grafts were performed. Of the operated patients 70% received complete arterial revascularization.

Results:
Early outcome revealed a procedural success of in all 55 pts for
CABG
and in 53 of 56 pts for
PCI
, three pts assigned to PCI had to be successfully converted to CABG. Early mortality in surgery was 1.8%, no patient died early after PCI. Periprocedural NSTEMI were noted in 2 pts after PCI and in six pts after CABG, of those one pt. underwent graft revision. After 12-month follow up control angiography was performed, in 2 pts (3,5%) after
CABG
and in 7 pts. after
PCI
(13,2%) reintervention was necessary. 5 pts required target vessel revascularization (TVR). 2 pts developed a de-novo lesion. One of the PCI cohort died at 10 months. MACE rate after 12 month was comparable for
CABG group
with 18,1% and 17,9% for the
PCI group
.

Conclusions:
In pts with nonprotected left main stenosis both CABG and PCI using drug eluting stents can be performed with few periprocedural complications, low mortality and at 12 months mace rate and survival compare favourably, reintervention rate is higher in PCI.
Abstract 1792: Multiple Biomarker Utilization for Detection of Myocardial Infarction Based on Presentation Sample in Patients with Symptoms Suggestive of Acute Coronary Syndrome
Authors: Apple Fred S , Smith Stephen W , Pearce Lesly A , Murakami MaryAnn M
Published: July 2021

OBJECTIVES: To determine if multiple biomarkers representative of numerous pathophysiologic pathways increase diagnostic accuracy for early detection of myocardial infarction (MI) in patients presenting with symptoms of acute coronary syndrome (ACS).

BACKGROUND: Cardiac troponin has been accepted as the preferred biomarker for detecting myocardial injury and acute myocardial infarction.

METHODS: Seven biomarkers (myeloperoxidase (MPO), soluble CD40 ligand (CD40L), placental growth factor (PIGF), metalloproteinase-9 (MMP-9), high sensitive C-reactive protein (hsCRP), cardiac troponin I (cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP)) were measured on admission plasma specimens and estimated glomerular filtration rate (eGFR) calculated in 457 patients presenting with symptoms suggestive of ACS. Median time from symptom onset to presentation was 3.1 hours. Twenty-five (5.4%) patients were diagnosed with acute MI (ICD 410.×1 code). Clinical sensitivities and specificities of each biomarker for AMI were determined based on 99
th
percentile reference values. Forward and backward stepwise logistic regression modeling techniques were used to identify biomarkers independently predictive of AMI.

RESULTS: Clinical sensitivity of the biomarkers ranged from 20% to 96% with specificity ranging from 19% to 89%. Highest clinical sensitivity was MMP-9 but specificity was only 19%. cTnI demonstrated a clinical sensitivity of 72% and specificity of 89% with false negatives occurring in 7 patients and false positives in 49. In multivariate models, cTnI (p < 0.001) and either hsCRP (p = 0.009) or MMP-9 (p = 0.03) and cTnI were independently predictive of AMI. hsCRP or MMP-9 increased specificity to 95% or 94% respectively but reduced sensitivity to 56% and 68% respectively relative to cTnI alone.

CONCLUSION: Our findings support utilization of cTnI alone, rather than a multi-biomarker approach, when using an analytically robust assay based on the 99
th
percentile reference value decision cutoff, as the most clinically accurate biomarker for the early diagnosis of AMI.
Abstract 1823: A Nursing Intervention Increases Knowledge, Attitudes and Beliefs About Response to Acute Coronary Syndrome in People with Coronary Heart Disease
Authors: McKinley Sharon , Doering Lynn V , Meischke Hendrika , Moser Debra K K , Riegel Brabara , Aitken Leanne M , Buckley Tom , Marshall Andrea , Pelter Michele , Dracup Kathleen
Published: July 2021

Background:
The largest contributor to delayed receipt of reperfusion therapy for acute coronary syndrome (ACS) is patient delay in recognizing symptoms and seeking treatment.

Objectives:
We tested the effect of an education and counseling intervention designed to reduce patient delay on knowledge, attitudes and beliefs about ACS symptoms and the response to symptoms.

Methods:
We conducted a 2-group randomized controlled trial in 3,522 people with coronary heart disease (CHD). The intervention group (n=1777) received a one-on-one education and counseling session from a cardiovascular nurse that addressed informational, emotional, and social responses associated with onset of ACS symptoms, followed by a telephone call at one month. The control group (n=1745) received usual care. Knowledge, attitudes and beliefs were measured at baseline and 3 and 12 months using the ACS Response Index. Repeated measures ANOVA was used to assess differences in outcomes over time.

Results:
Patients were 67±11 years old; 67% were male and 45% had history of AMI. Knowledge, attitudes and beliefs scores increased significantly from baseline in the intervention group compared to the control group at 3 months and remained higher at 12 months (Table

).

C
onclusion:
A relatively short one-on-one education and counseling intervention significantly increased knowledge, attitudes and beliefs about ACS and response to ACS symptoms, sustained to 12 months following the intervention. The results of the study suggest that individualized education for those at high risk of ACS is effective in increasing the knowledge, attitudes and beliefs required to make an appropriate decision about seeking care for ACS.

Table.

Mean scores for knowledge, attitudes and beliefs by group over time
Abstract 1825: Abnormal ECG Markers suggest that Accentuated Intracardiac Conduction Delay is The Common and Distinguishing Feature of Patients with Spontaneous Type 1 ECG or SCN5A Mutation in Brugadas Syndrome
Authors: Theilade Juliane , Bloise Raffaella , Nastoli Janny , Ronchetti Elena , Facchinetti S. , Rossenbacker Tom , Napolitano Carlo , Priori Silvia G
Published: July 2021

The conclusive diagnosis of Brugada Syndrome (BrS) is established in patients (pts) with spontaneous type 1 ECG or in carriers of a loss of function SCN5A mutation. We carried out a systematic analysis of ECG recordings in BrS pts to test the hypothesis that the presence of intraventricular (Intra-Ven) and atrioventricular (A-Ven) conduction delay is the distinguishing common feature of pts with SCN5A mutations (Mut+) and in pts with a spontaneous type 1 ECG pattern (spont-ECG). We assessed the following 5 ECG parameters: late potentials (quantified as RMS at 40 Hz), aVR sign (relative size of the R and q waves in aVR), QRS complex fragmentation (defined as an additional R′ or notching of the of S wave), PQ and QRS duration. We studied 200 consecutive BrS pts to define whether the prevalence of ECG markers correlate with 1) the presence of a SCN5A mutation (Mut+) or 2) the presence of a spontaneous type 1 pattern ECG (spont-ECG). Results are summarized in the table

. Interestingly, Mut+ not only presented prolonged PQ (p<0.003 vs Mut÷) as previously reported but more significantly they showed the presence of abnormal markers of intraventricular conduction (QRS duration, aVR sign and late potentials). Similarly, also the presence of a spont-ECG was associated with prolonged PQ and QRS intervals and with late potentials. Based on our ECG analysis we propose that

Brugada syndrome is a disease characterized by impairment of A-Ven and Intra-Ven conduction,

the presence of a mutation in the SCN5A gene and,

the presence of a spontaneous type 1 ECG identify patients with accentuated conduction defects.

These findings suggest that the presence of interventricular conduction delay is a landmark of BrS and should be considered as diagnostic markers in BrS.
Abstract 292: Validation of a Peripheral Blood Mononuclear Cell Gene Expression Network. A Systems Biological Approach to the Identification of Immunomodulatory Gene Targets.
Authors: Cadeiras Martin , von Bayern Manuel P , Sinha Anshu , Lim Wei-Keat , Palomero Teresa , Dedrick Russel , Marboe Charles C , Suciu-Foca Nicole , Califano Andrea , Deng Mario C
Published: July 2021

Background:
Reconstruction of intracellular networks underlying complex processes is a formidable challenge. We hypothesized that the human peripheral blood mononuclear cell (PBMC) molecular network can be delineated using a systems-biological/computer-driven approach.

Method:
We used a large PBMC microarray library, an information-theoretic, reverse-engineering algorithm (ARACNe, Algorithm for the Reconstruction of Accurate Cellular Networks) and Chromatin Immunoprecipitation (ChIP) assay to reconstruct and validate a putative gene interaction network.

Results:
Gene expression data from 285 focused-microarrays obtained from 98 heart transplant patients enrolled in the Cardiac Allograft Rejection Gene expression Observational (CARGO) study was analyzed by ARACNe to identify highly connected “hub” genes. Biological criteria identified Transcription Factor CREB and its subnetwork as important candidates involved in the regulation of the alloimmune response. ARACNe predicted 29 putative direct interactions (first neighbor genes) of CREB (Fig. 1A

). Eleven of these (Fig. 1A

red nodes) were previously reported (p<0.001) and 18 were not (Fig 1A

, pink nodes). Out of the non validated, 14 suitable primers were identified and 11 could be immunoprecipitated (Fig 1B

), demonstrating binding of CREB to their promoter in vivo. Overall, 22 (75%) inferred CREB targets were validated; a significantly higher fraction than randomly expected (p<0.001, Fisher’s exact).

Conclusion
Our results confirm the accuracy of ARACNe to reconstruct the PBMC transcriptional network. Systems biological approaches may be used to identify immunomodulatory pharmacological targets.

Figure 1
Abstract 1839: Characterization of the Mitral Isthmus during Atrial Fibrillation Ablation Using Intracardiac Ultrasound from Within the Coronary Sinus.
Authors: West J J , Norton Patrick T , Kramer Christopher M , Mounsey J P , Moorman J R , Mahapatra Srijoy , Dimarco John P , Mangrum J M , Ferguson John D
Published: July 2021

Background: Atrial fibrillation (AF) ablation involving the mitral isthmus and/or the coronary sinus (CS) is complex and may result in circumflex artery (Cx) damage or other complications. We investigated the feasibility of intracardiac echocardiographic (ICE) imaging from within the CS to characterize mitral isthmus anatomy and guide ablation.

Methods: A 9F sheath was introduced into the CS of 30 patients prior to AF ablation. A 9F rotational ICE catheter was then advanced within the sheath to the distal CS adjacent to the lateral left atrial wall. Serial cross-sectional images to document the relations of the left atrium, Cx, CS, esophagus and pericardium were obtained at multiple points within the CS during a pull-back to the CS ostium.

Results: The Cx was < 20mm from the CS in 62/150 positions, in 25/30 patients. In these patients, the median(range) LA-Cx distance was 3.3mm(0.7–19.6mm) and median CS-Cx distance was 2.0mm(0.4–9.7mm). The esophagus was seen < 20mm from the CS in 36/150 positions, in 17/30 patients. Median CS-esophagus distance was 4.0mm(1.4–16.2mm). Proximity of the Cx and esophagus to the left atrium and CS varied considerably. The median CS-mitral annulus distance was 11.9mm(4.1–21.6mm). After CS cannulation, the ICE imaging took 5±2 minutes and required 120±60 seconds of fluoroscopy.

Conclusions: The variable relationships of the Cx and esophagus relative to the mitral isthmus can be accurately characterized by rotational ICE imaging from within the CS. This is a useful adjunct to ICE imaging from within the atria. Real-time identification of these structures could help to locate optimal ablation sites and potentially reduce complications.
Abstract 1853: Desmopressin Acetate Reduces Blood Loss After Cardiac Surgery: A Double-bind Randomized Controlled Trial
Authors: Hajjar Ludhmila A , Galas Filomena , Fortim Monica , Melo Renato , Ferreira Rosa , Auler Jose Otavio
Published: July 2021

It has been suggested that desmopressin acetate (DDAVP) administration reduces blood loss after cardiac surgery. It acts by releasing von Willebrand factor multimers from endothelial cells, leading to an increase in plasma levels of von Willebrand factor and an enhancement of primary hemostasis. We have investigated the effect of DDAVP administration in a double-blind, randomized, prospective trial including 150 patients placed on cardiopulmonary bypass. Seventy-five patients received 0.3 micrograms/kg DDAVP and 75 patients received a placebo administered in a 50 ml saline solution over 15 min immediately after end of surgery. Results showed significant differences in total blood loss per square meter (258 +/− 106 ml in the DDAVP group vs 526 +/− 314 ml in the placebo group, p<0.001), and in necessity for red cell transfusions (1142 +/− 205 ml in the DDAVP group vs 1774 +/− 385 ml in the placebo group, p<0.005) in the first 72 hr after surgery. The prolongation of bleeding time and the decrease of factor VIII:C and factor VIII:von Willebrand factor 90 min after treatment were significantly lower (p less than .001) in the DDAVP group as compared with the placebo group. The rate of thrombosis and cardiac necrosis did not differ significantly between groups (p>0.05). In conclusion, the administration of DDAVP in patients placed on cardiopulmonary bypass reduces total blood loss and needing of transfusion, without resulting in higher rates of complications.
Abstract 1863: Cell-Based Therapy without Cell Transplantation: Tissue Engineering of an Acellular Matrix for the Recruitment of Endogenous Circulating Progenitor Cells
Authors: Suuronen Erik J , Cao Xudong , Melhuish Angela , McKee Daniel , Hazra Samir , Zhang Pingchuan , Li Fengfu , Mesana Thierry G , Veinot John P , Ruel Marc
Published: July 2021

Objectives:
Following a cardiac event, circulating progenitor cells can home and engraft to sites of neovascularization, mediated in part by the adhesion molecule L-selectin; however, accumulation in the heart is low. We developed an acellular matrix containing the oligosac-charide sialyl Lewis
X
(sLe
X
; 0.1mM), which binds L-selectin, in order to specifically enhance the engraftment of endogenous circulating progenitor cells.

Methods:
Adhesion and phenotype of CD133
+
and CD34
+
progenitor cells on sLe
X
-collagen or collagen matrix were assessed, and the role of L-selectin was characterized by blocking experiments. In animal work, a double hindlimb ischemic rat model was used (N=8): one hindlimb was injected with sLe
X
-collagen matrix, and the other with collagen matrix (200μl each). Rats underwent laser Doppler perfusion analysis at 0, 7 and 14 days post-operation. Two-week tissue was analysed by immunohistochemistry.

Results:
Cell adhesion was greater on sLe
X
-collagen matrix (9.0± 2.3%) as compared to collagen matrix (4.3± 2.6%), and was reduced by pre-incubating cells with sLe
X
(2.8± 1.3%) or anti-L-selectin (2.7± 1.0%; P< 0.001), demonstrating a role for sLe
X
in enhanced adhesion mediated by L-selectin binding. The proportion of CD133
+
CD34
+
L-selectin
+
cells was greater in the adherent population (8.1±3.4%) than in the non-adherent population (1.9±1.4%; P<0.001), indicating active recruitment of vasculogenic progenitors. Also, the sLe
X
-collagen matrix recruited 3.2±1.4 fold more CD133
+
CD34
+
L-selectin
+
cells than the collagen matrix (P<0.05). Rat ischemic hindlimbs treated with sLe
X
-collagen matrix recruited a greater number of CD133
+
and c-kit
+
progenitor cells (3.0±1.0 and 2.1±1.0 fold, respectively; P<0.05) vs. collagen matrix treatment. The increase in progenitor cell engraftment was associated with a 3.8±1.1 fold greater intramuscular arteriole density (P<0.001) and with a 54% increase in hindlimb perfusion in sLe
X
-collagen matrix treated limbs (P<0.05).

Conclusions:
The sLe
X
-collagen matrix selectively enhances progenitor cell homing/engraftment mechanisms and endogenous cell-based tissue repair. Effectively, we have achieved progenitor cell-based therapy without the need for actual transplantation of cells.
Abstract 1865: Real-Time 3D Transesophageal Echocardiography in the Guidance of Atrial Septal Defect Closure: Comparison with Intracardiac and 2D Transesophageal Echocardiography
Authors: Lodato Joseph A , Cao Qi Ling , Weinert Lynn , Sugeng Lissa , Lang Roberto M , Hijazi Ziyad M
Published: July 2021

Background:
Intracardiac echocardiography (ICE) is the preferred method for deployment of Amplatzer septal occluder devices (ASOD) in patients with atrial septal defect (ASD). Because ICE is costly and not widely available, 2D transesophageal echocardiography (2D-TEE) is often used instead. However, ASDs can have complex oval shapes that may not be well characterized with 2D imaging. We hypothesized that a new real-time 3D TEE (RT3D-TEE) probe could provide dynamic en-face visualization of the ASD and thus allow precise assessment of ASD dimensions.

Aims:

To determine the feasibility of using RT3D-TEE in the guidance of ASOD deployment in patients with ASD, and

to compare the size of ASD and the occluding balloon waist obtained using RT3D-TEE against ICE and 2D-TEE.

Methods:
8 consecutive patients with ostium secundum ASD (age 36±11 yrs) underwent ASOD placement under general anesthesia. Biplane 2D-TEE, RT3D-TEE and ICE images were acquired (Philips iE33) sequentially throughout ASOD placement. Measurements were obtained on-line.

Results:
Closure was successful in all patients without complications. RT3D-TEE was feasible yielding high quality images suitable for measurements (Table). ASD size by RT3D-TEE differed by >1mm from 2D-TEE and ICE in 2 and 3 patients respectively in the long axis view and in 3 and 4 patients in the short axis view. Balloon waist size was 25.5 ± 6.7 (16–37) by 3D TEE and 24.7 ± 6.5 (15–35) by ICE.

Conclusions:
RT3D-TEE can be used for guidance of ASOD deployment with the advantage of improved ability compared to 2D-TEE and ICE to visualize the true en-face views, from which accurate measurements of ASD dimensions can be made for device selection.
Abstract 134: Extracellular ATP Inhibits Natural Killer Cell Recruitment in Inflamed Tissues and Protects Endothelial Cells From NK-Mediated Vascular Injury
Authors: Gorini Stefania , Mammi Caterina , Ferrari Davide , Callegari Giulia , Di Virgilio Francesco , Gatta Lucia , Consoli Claudia , Caprio Massimiliano , Volterrani Maurizio , Rosano Giuseppe , Stabile Eugenio , Montevergine Clinca , la Sala Andrea
Published: July 2021

Background: Natural killer cells (NK) represent the main source of IFN-gamma that contributes to atherosclerotic plaque progression and instability. Fractalkine (CX3CL1) expressed by endothelial cells (ECs) mediate NK recruitment and elicit NK-mediated ECs killing. Moreover high CX3CL1 mRNA expression has been found in advanced atherosclerotic lesions of human arteries as well as in the deep intima of diabetic patients. Nucleotides can be massively released in the extracellular space by ECs under shear stress, activated platelets and injured cells and stimulate purinergic receptors expressed in different cell types including NK.

Hypothesis: that extracellular nucleotides modify NK responses to CX3CL1 or SDF-1 (CXCL12) and their ability to mediate vascular injury.

Methods: NK were isolated by negative immunomagnetic selection from peripheral blood of healthy blood donors and P2 receptor genes expression pattern studied by RT-PCR. NK chemotaxis was measured by transwell cell culture system followed by flow cytometric analysis of migrated cells. NK were co-cultured with HUVEC cells to analyze NK-mediated ECs killing.

Results: we show for the first time that NK express P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, P2Y14 and P2X1, P2X4, P2X7 receptors. Neither ATP or UTP alone induced NK cell migration. However ATP but not UTP increased non-directional cell movement (chemokinesis). This effect was mimicked by the cell permeable cyclic AMP analogue 8-Br-cAMP and was dependent on Protein kinase A activity since it was blocked by the specific inhibitor H89. In addition, ATP but not UTP, inhibited NK cell chemotaxis to CX3CL1 whereas expression for CXCR4 and migration following CXCL12 stimulation were increased. Moreover the NK-mediated killing of HUVEC cells was downregulated following exposure to extracellular ATP.

Conclusion: CX3CL1 has been shown to participate to leukocyte adhesion to ECs and extravasation. In addition membrane bounds form of CX3CL1 expressed by ECs triggers NK cytotoxicity. ATP release from endothelial cells upon shear stress and in inflammatory states might represent a protective mechanism from NK cell-mediated cytotoxicity and point out P2 purinergic receptors as novel potential therapeutic targets.