Technical success and long-term outcomes after anomalous right coronary artery stenting with cardiac computed tomography angiography correlation.

INTRODUCTION: Anomalous origin of coronary arteries has been observed in about 0.35-2.10% of the population. Patients with anomalous right coronary artery (ARCA) may present with significant symptoms, arrhythmias or ACS, and at times sudden death. Traditionally, surgical correction has been the recommended treatment. However, these may be technically challenging, and bypass grafting for such anomalies has the potential for graft failure because of competitive flow. We sought to determine the intermediate and long-term outcomes of drug-eluting stent placement for patients with symptomatic ARCA. We also looked at angiographic findings suggestive of interarterial course as confirmed by subsequent computed tomography (CT) findings. METHODS: Between January 2005 and December 2012, we enrolled 11 patients for elective percutaneous coronary intervention (PCI) of ARCA in a single center, prospective, nonrandomized fashion. Patients were followed up in clinic at 1 week, 3 months, 6 months, and 1 year, and then annually or more frequently if needed. All patients underwent a cardiac CT, as well as functional stress testing when needed to assess for recurrence of disease. RESULTS: All 11 of our patients, who presented with significant symptomatic stenosis with an ARCA, were successfully treated with PCI. Mean follow-up duration was 8.5 years. The only two deaths during follow-up were related to noncardiac causes (sepsis), with a mortality rate of 18.2%. Two patients had a positive functional study and on subsequent coronary angiography, one of them had significant in-stent restenosis (target lesion revascularization of 9.1%) and one distal to the stent (target vessel revascularization 9.1%). We found the observation of a "slit-like lesion" on angiography to have a sensitivity of 100% and specificity of 86% for the diagnosis of interarterial course of the anomalous vessel seen on subsequent CT. CONCLUSIONS: Our study results suggest that PCI of ARCA is an effective and low-risk alternative to surgical correction, with good procedural success and long-term outcomes. It can provide symptomatic relief in such patients and may reduce the risk of sudden death in younger patients, without the inherent risks associated with surgical repair.

A Comparison of Theory-Based and Experimentally Determined Myocardial Signal Intensity Correction Methods in First-Pass Perfusion Magnetic Resonance Imaging.

OBJECTIVES: To evaluate the impact of correcting myocardial signal saturation on the accuracy of absolute myocardial blood flow (MBF) measurements. MATERIALS AND METHODS: We performed 15 dual bolus first-pass perfusion studies in 7 dogs during global coronary vasodilation and variable degrees of coronary artery stenosis. We compared microsphere MBF to MBF calculated from uncorrected and corrected MRI signal. Four correction methods were tested, two theoretical methods (Th1 and Th2) and two empirical methods (Em1 and Em2). RESULTS: The correlations with microsphere MBF (n = 90 segments) were: uncorrected (y = 0.47x + 1.1, r = 0.70), Th1 (y = 0.53x + 1.0, r = 0.71), Th2 (y = 0.62x + 0.86, r = 0.73), Em1 (y = 0.82x + 0.86, r = 0.77), and Em2 (y = 0.72x + 0.84, r = 0.75). All corrected methods were not significantly different from microspheres, while uncorrected MBF values were significantly lower. For the top 50% of microsphere MBF values, flows were significantly underestimated by uncorrected SI (31%), Th1 (25%), and Th2 (19%), while Em1 (1%), and Em2 (9%) were similar to microsphere MBF. CONCLUSIONS: Myocardial signal saturation should be corrected prior to flow modeling to avoid underestimation of MBF by MR perfusion imaging.

Femtomole immunodetection of synthetic and endogenous amyloid-beta oligomers and its application to Alzheimer's disease drug candidate screening.

Alzheimer's disease (AD) is a fatal, progressive dementia for which there is no cure and for which a molecular basis has yet to be established. However, considerable evidence suggests that AD is linked to neurotoxic assemblies of the 42-amino-acid peptide amyloid beta (Abeta). There is now a clear body of evidence that shows this neurotoxicity resides not only in insoluble fibrils of Abeta but also in soluble Abeta ADDLs (Abeta-derived diffusible ligands) and larger protofibrils. Further, anti-Abeta antibodies have been reported to reverse memory failure in human amyloid precursor protein (hAPP)-expressed transgenic mice in a manner that suggests symptom reversal is attributable to targeting of ADDLs. Clearly, a search for drugs targeting the assembly of these soluble Abeta species represents a new and potentially important approach to the treatment of AD. In this work we describe the development of a dot-blot immunoassay to measure ADDL at the femtomole level, its use in defining the time course of ADDL formation, and its use in determining the presence of ADDLs in the hAPP transgenic mouse brain. Discussion of a protocol to screen agents for inhibition of neurotoxic ADDLformation both in vivo and in vitro is also presented. The methods are suitable for screening combinatorial libraries and, importantly, provide the potential for simultaneous information on candidate transport across the blood-brain barrier.

Per-6-substituted beta-cyclodextrin libraries inhibit formation of beta-amyloid-peptide (A beta)-derived, soluble oligomers.

Alzheimer's disease is the most common cause of dementia in older individuals with compelling evidence favoring neuron dysfunction and death triggered by assembled forms of A beta(1-42). While large neurotoxic amyloid fibrils have been known for years, recent studies show that soluble protofibril and A beta(1-42)-derived diffusible ligands (ADDLs) may also be involved in neurotoxicity. In the present work, dot-blot immunoassays discriminating ADDLs from monomers were used to screen libraries of per-substituted beta-cyclodextrin (beta-CD) derivatives for inhibition of ADDLs formation. Libraries were prepared from per-6-iodo-beta-CD by treatment with various amine nucleophiles. The most active library tested (containing >2000 derivatives) was derived from imidazole, N, N-dimethylethylenediamine and furfurylamine, which at 10 microM total library, inhibited ADDLs formation (10 nM A beta(1-42)) over a period of 4 hours. The latter was confirmed by a western blot assay showing decreased amounts of the initially formed A beta(1-42) tetramer. These preliminary experiments suggest that derivatized forms of beta-CD can interfere with the oligomerization process of A beta(1-42).