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Background: Routine clinical use of novel free-breathing, motion-corrected, averaged late-gadolinium-enhancement (moco-LGE) cardiovascular MR may have advantages over conventional breath-held LGE (bh-LGE), especially in vulnerable patients., Methods and Results: In 390 consecutive patients, we collected bh-LGE and moco-LGE with identical image matrix parameters. In 41 patients, bh-LGE was abandoned because of image quality issues, including 10 with myocardial infarction. When both were acquired, myocardial infarction detection was similar (McNemar test, P=0.4) with high agreement (κ=0.95). With artifact-free bh-LGE images, pixelwise myocardial infarction measures correlated highly (R(2)=0.96) without bias. Moco-LGE was faster, and image quality and diagnostic confidence were higher on blinded review (P<0.001 for all). During a median of 1.2 years, 20 heart failure hospitalizations and 18 deaths occurred. For bh-LGE, but not moco-LGE, inferior image quality and bh-LGE nonacquisition were linked to patient vulnerability confirmed by adverse outcomes (log-rank P<0.001). Moco-LGE significantly stratified risk in the full cohort (log-rank P<0.001), but bh-LGE did not (log-rank P=0.056) because a significant number of vulnerable patients did not receive bh-LGE (because of arrhythmia or inability to hold breath)., Conclusions: Myocardial infarction detection and quantification are similar between moco-LGE and bh-LGE when bh-LGE can be acquired well, but bh-LGE quality deteriorates with patient vulnerability. Acquisition time, image quality, diagnostic confidence, and the number of successfully scanned patients are superior with moco-LGE, which extends LGE-based risk stratification to include patients with vulnerability confirmed by outcomes. Moco-LGE may be suitable for routine clinical use.

Objective: The methodology for use of cardiac CT angiography (CTA) in low risk populations is not well defined. In order to present a reference for future studies, we present CTA methodology that is being used in an epidemiology study- the Multicenter AIDS Cohort Study (MACS)., Methods: The Multicenter AIDS Cohort Study (MACS) is an on-going multicenter prospective, observational cohort study. The MACS Cardiovascular Disease substudy plans to enroll 800 men (n= 575 HIV seropositive and n=225 HIV seronegative) age 40-70 years for coronary atherosclerosis imaging using cardiac CTA. The protocol includes heart rate (HR) optimization with beta- blockers; use of proper field of view; scan length limitation; prospective ECG-gating using the lowest beam voltage possible. All scans are evaluated for presence, extent, and composition of coronary atherosclerosis, left atrial volumes, left ventricular volume and mass and non-coronary cardiac pathology., Results: The first 498 participants had an average radiation dose of 2.5±1.6 milliSieverts (mSv) for the cardiac CTA study. Overall quality of scans was fair to excellent in 98.6% of studies. There were three significant adverse events-two allergic reactions to contrast and one subcutaneous contrast extravasation., Conclusion: Cardiac CTA was safe and afforded a low effective radiation exposure to these asymptomatic research participants and provides valuable cardiovascular endpoints for scientific analysis. The cardiac CTA methodology described here may serve as a reference for use in future epidemiology studies aiming to assess coronary atherosclerosis and cardiac anatomy in low risk populations while minimizing radiation exposure.

Purpose: To investigate the prevalence of aortic root dilation in patients who underwent CT angiography of the thoracic aorta., Materials and Methods: In 95 patients, 64-slice multislice computed tomography was performed for evaluation of the thoracic aorta. Measurements of the annulus, sinuses of valsalva (SOV), sinotubular junction (STJ), and maximum ascending aorta (AAo) were made by double oblique multiplanar reformation (MPR). For the AAo, STJ, and SOV, dilation was defined as greater than 40 mm; for annulus, the dilation criterion was greater than 27 mm., Results: Overall, 52 patients were diagnosed with a dilated AAo. Of those patients with dilated AAo, 28 patients had a dilated annulus, 27 patients had dilated SOV, and 11 patients had STJ dilation. Forty-three patients presented with normal AAo; 12 patients had annulus dilation; 12 patients had SOV dilation; and 4 patients had STJ dilation. In patients with dilated AAo, 38% also had a dilated annulus, 52% showed SOV dilation, and 21% presented with STJ dilation, compared to 28% annulus dilation, 28% SOV dilation, and 9% STJ dilation in patients with an AAo of normal caliber., Conclusion: Our data indicate a higher prevalence of aortic root dilation among patients with dilated AAo.

Aims: Lone atrial fibrillation (LAF) is considered by some to be a primary atrial electrophysiologic disorder. However, we have frequently observed evidence of "extraatrial" diseases - atherosclerosis and associated metabolic disorders - in our LAF patients. We sought to characterize and quantify extraatrial disease burden in LAF patients, and to correlate this burden with features of the arrhythmia including pattern (paroxysmal versus persistent) and response to catheter ablation., Methods and Results: Forty-six consecutive patients with non-familial LAF underwent assessment for evidence of atherosclerosis (computed tomographic vascular calcification and elevated arterial pulse wave velocity) and associated metabolic diseases (dyslipidemia, insulin resistance and inflammation), and then catheter ablation. The cohort had a significant incidence of atherosclerosis (57%) and metabolic (70%) diseases. Patients with persistent AF tended to have a greater extraatrial disease burden than those with paroxysmal AF. A significant inverse relationship between the rate of ablation success and extraatrial disease burden was demonstrated., Conclusions: Extraatrial disease was common in this LAF cohort. Correlations between extraatrial disease burden and features of the arrhythmia would, if verified, challenge the notion that LAF is a "primary" electrophysiologic disorder.

Background: Platelet deposition after angioplasty remains problematic and may contribute to intimal hyperplasia and restenosis. We proposed that polyethylene glycol diisocyanate (PEG-DISO), a polymer that rapidly forms covalent linkages with amine residues on proteins, could mask thrombogenic vascular wall proteins from platelets, thereby abrogating acute platelet deposition., Methods and Results: To test this hypothesis, we isolated the femoral arteries of 10 New Zealand White rabbits and injured them with 3 passes of a 2F Fogarty catheter which was inserted through a distal arteriotomy. Immediately after balloon injury, (111)indium-labeled autologous platelets were infused peripherally and the injured femoral arteries were randomly treated for 1 minute with a PEG-DISO solution in one artery and a control solution of the phosphate buffered saline vehicle in the contralateral artery. Following treatment, reflow was initiated. The vessels were harvested after 1 hour and radioactivity was quantified in a gamma counter. Platelet counts were standardized by weight and expressed as platelets/mg (mean +/- SEM). Platelet deposition onto arteries treated with PEG-DISO was (1.2 +/- 0.5) x 10(6) platelets/mg compared to (5.6 +/- 4.2) x 10(6) platelets/mg onto the contralateral control arteries treated with vehicle (P < 0.005). Scanning electron micrographs of the injured vessel segment confirmed qualitatively less platelet deposition on the treated segments than on the control segments., Conclusion: Treatment with PEG-DISO significantly inhibited platelet deposition after vascular injury. These data support the hypothesis that treatment with PEG-DISO masks surface adhesive proteins from platelet receptors in vivo and that the resulting molecular barrier significantly reduces platelet deposition onto the damaged vessel wall for at least one hour. The formation of a molecularly thin barrier to platelet deposition may thus be a novel and effective treatment to abrogate acute intravascular thrombosis and may have value in the treatment of restenosis.

For cardiovascular biomaterials, thrombosis, thromboembolism and vascular graft occlusion are believed to be precipitated by the adsorption of proteins containing adhesive ligands for platelets. Polyethylene-glycol-diisocyanate(PEG-diisocyanate, 3400 MW) may potentially react with protein amines to form molecular barriers on adsorbed proteins on biomaterials, thereby masking adhesive ligands and preventing acute surface thrombosis. To test this notion, PE, PTFE, and glass microconduits were pre-adsorbed with fibrinogen and treated with PEG-diisocyanate, non-reactive PEG-dihydroxyl, or remained untreated. Following perfusion of 111In-labeled platelets in whole human blood for 1 min (wall shear rate = 312 s(-1)), PEG-diisocyanate treated surfaces experienced 96%(PE), 97%(PTFE) and 94% (glass) less platelet deposition than untreated surfaces. Similar reductions were seen for PEG-diisocyanate versus PEG-dihydroxyl treatment. Low shear perfusions of plasma for one hour prior to blood contact did not reduce the inhibitory effect of PEG-diisocyanate. Platelet adhesion onto collagen coated glass coverslips and platelet deposition onto preclotted Dacron was also reduced by treatment with PEG-diisocyanate (93 and 91%, respectively). Protein-reactive PEG may thus have utility in forming molecular barriers on surface associated proteins to inhibit acute thrombosis on cardiovascular biomaterials.

For cardiovascular biomaterials, thrombosis, thromboembolism and vascular graft occlusion are believed to be precipitated by the adsorption of proteins containing adhesive ligands for platelets. Polyethylene-glycol-diisocyanate (PEG-diisocyanate, 3400 MW) may potentially react with protein amines to form molecular barriers on adsorbed proteins on biomaterials, thereby masking adhesive ligands and preventing acute surface thrombosis. To test this notion, PE, PTFE, and glass microconduits were pre-adsorbed with fibrinogen and treated with PEG-diisocyanate, non-reactive PEG-dihydroxyl, or remained untreated. Following perfusion of 111In-labeled platelets in whole human blood for 1 min (wall shear rate = 312 s(-1)), PEG-diisocyanate treated surfaces experienced 96% (PE), 97% (PTFE) and 94% (glass) less platelet deposition than untreated surfaces. Similar reductions were seen for PEG-diisocyanate versus PEG-dihydroxyl treatment. Low shear perfusions of plasma for 1 h prior to blood contact did not reduce the inhibitory effect of PEG-diisocyanate. Platelet adhesion onto collagen-coated glass coverslips and platelet deposition onto preclotted Dacron were also reduced by treatment with PEG-diisocyanate (93 and 91%, respectively). Protein-reactive PEG may thus have utility in forming molecular barriers on surface-associated proteins to inhibit acute thrombosis on cardiovascular biomaterials.

We report here a novel method for blocking acute platelet deposition at the site of vessel injury by molecularly masking thrombogenic vascular wall proteins with covalently attached polyethylene glycol (PEG). To evaluate this technique, blood containing 111In-labeled platelets was perfused over damaged human placental arteries for 2 min at a wall shear rate of 200 s-1. Denuded vessel segments were incubated for 30, 15, 5, and 1 min with a solution of either reactive PEG-diisocyanate (PEG-ISO) or nonreactive PEG-dihydroxyl (PEG-OH). Vessels treated with PEG-ISO for 1 min exhibited 87 +/- 12% less platelet deposition (p < 0.01) than untreated control vessels, and this reduction did not vary significantly among treatment times, indicating that this reaction occurs rapidly enough to be clinically applicable. To investigate the duration of this thrombotic barrier, denuded pig carotid arteries were treated with reactive PEG-ISO for 1 min, perfused with plasma for 30 min, and then perfused with blood containing radiolabeled platelets. PEG-ISO-treated arteries exhibited 84 +/- 9% less platelet deposition (p < 0.05) than untreated controls. These data demonstrate that damaged arterial surfaces can be rendered resistant to platelet deposition after short contact periods with reactive PEG. Molecular PEG barriers ultimately might find application following vascular procedures to sterically inhibit blood cell interaction with damaged vascular surfaces.