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Item Atherosclerosis Imaging with 18F-Sodium Fluoride PET(MDPI, 2020-10-20) Høilund-Carlsen, Poul F.; Piri, Reza; Constantinescu, Caius; Iversen, Kasper Karmark; Werner, Thomas J.; Sturek, Michael; Alavi, Abass; Gerke, Oke; Anatomy and Cell Biology, School of MedicineThe evidence on atherosclerosis imaging with 18F-sodium-fluoride (NaF) positron emission tomography (PET) is hotly debated because of the different patient characteristics, methodology, vascular beds, etc. in reported studies. This review is a continuation of a previous review on this topic, which covered the period 2010–2018. The purpose was to examine whether some of the most important questions that the previous review had left open had been elucidated by the most recent literature. Using principles of a systematic review, we ended analyzing 25 articles dealing with the carotids, coronary arteries, aorta, femoral, intracranial, renal, and penile arteries. The knowledge thus far can be summarized as follows: by targeting active arterial microcalcification, NaF uptake is considered a marker of early stage atherosclerosis, is age-dependent, and consistently associated with cardiovascular risk. Longitudinal studies on NaF uptake, conducted in the abdominal aorta only, showed unchanged uptake in postmenopausal women for nearly four years and varying uptake in prostate cancer patients over 1.5 years, despite constant or increasing calcium volume detected by computed tomography (CT). Thus, uncertainty remains about the transition from active arterial wall calcification marked by increased NaF uptake to less active or consolidated calcification detected by CT. The question of whether early-phase atherosclerosis and calcification can be modified remains also unanswered due to lack of intervention studies.Item Coronary artery disease progression and calcification in metabolic syndrome(2014) McKenney, Mikaela Lee; Sturek, Michael Stephen; Evans-Molina, Carmella; Moe, Sharon M.; Tune, Johnathan D.For years, the leading killer of Americans has been coronary artery disease (CAD), which has a strong correlation to the U.S. obesity epidemic. Obesity, along with the presence of other risk factors including hyperglycemia, hypercholesterolemia, dyslipidemia, and high blood pressure, comprise of the diagnosis of metabolic syndrome (MetS). The presentation of multiple MetS risk factors increases a patients risk for adverse cardiovascular events. CAD is a complex progressive disease. We utilized the superb model of CAD and MetS, the Ossabaw miniature swine, to investigate underlying mechanisms of CAD progression. We studied the influence of coronary epicardial adipose tissue (cEAT) and coronary smooth muscle cell (CSM) intracellular Ca2+ regulation on CAD progression. By surgical excision of cEAT from MetS Ossabaw, we observed an attenuation of CAD progression. This finding provides evidence for a link between local cEAT and CAD progression. Intracellular Ca2+ is a tightly regulated messenger in CSM that initiates contraction, translation, proliferation and migration. When regulation is lost, CSM dedifferentiate from their mature, contractile phenotype found in the healthy vascular wall to a synthetic, proliferative phenotype. Synthetic CSM are found in intimal plaque of CAD patients. We investigated the changes in intracellular Ca2+ signaling in enzymatically isolated CSM from Ossabaw swine with varying stages of CAD using the fluorescent Ca2+ indicator, fura-2. This time course study revealed heightened Ca2+ signaling in early CAD followed by a significant drop off in late stage calcified plaque. Coronary artery calcification (CAC) is a result of dedifferentiation into an osteogenic CSM that secretes hydroxyapatite in the extracellular matrix. CAC is clinically detected by computed tomography (CT). Microcalcifications have been linked to plaque instability/rupture and cannot be detected by CT. We used 18F-NaF positron emission tomography (PET) to detect CAC in Ossabaw swine with early stage CAD shown by mild neointimal thickening. This study validated 18F-NaF PET as a diagnostic tool for early, molecular CAC at a stage prior to lesions detectable by CT. This is the first report showing non-invasive PET resolution of CAC and CSMC Ca2+ dysfunction at an early stage previously only characterized by invasive cellular Ca2+ imaging.Item Procedural and long-term ischemic outcomes of tight subtotal occlusions treated with orbital atherectomy: An ORBIT II subanalysis(Elsevier, 2018) Lee, Michael S.; Shlofmitz, Richard A.; Shlofmitz, Evan; Behrens, Ann N.; Revtyak, George; Martinsen, Brad J.; Chambers, Jeffrey W.; Medicine, School of MedicineBackground/purpose Orbital atherectomy is an effective treatment strategy to modify severely calcified coronary lesions prior to stent placement. Traversing a severely calcified subtotal occlusion with the crown may be more challenging compared with a less severely stenotic lesion. The purpose of this ORBIT II subanalysis was to evaluate outcomes post-orbital atherectomy (OA) treatment of lesions with ≥95% stenosis. Methods/materials ORBIT II, a single-arm, prospective, multicenter trial, enrolled 443 subjects with severely calcified coronary lesions. Patients with chronic total occlusions were excluded from the trial. Subjects with the OA device activated were stratified based on pre-procedure percent stenosis: ≥95% stenosis (N = 91) and <95% stenosis (N = 341). Procedural success and 3-year major adverse cardiac event (MACE) rates were compared. Results The severe angiographic complications rates were 6.6% and 6.7% in the ≥95% and <95% stenosis groups, respectively. There was no significant difference in procedural success (94.5% vs. 88.3%, p = 0.120). 3-year MACE rates were similar (27.1% vs. 22.5%, p = 0.548), as were the rates of cardiac death (5.7% vs. 7.1%, p = 0.665) and MI (7.9% vs. 12.1%, p = 0.244). The TVR rate was higher in the ≥95% stenosis group (19.1% vs. 7.5%, p = 0.004). Conclusions In ORBIT II, OA treatment of lesions with ≥95% stenosis resulted in a high rate of procedural success. Although the 3-year revascularization rate was higher in the ≥95% stenosis group, it is not unexpected given the challenge of treating such complex lesions. The results of this analysis suggest that OA may be a reasonable treatment strategy for tight, severely calcified subtotal occlusions. Summary The purpose of this ORBIT II subanalysis was to evaluate outcomes post-orbital atherectomy (OA) treatment of lesions with ≥95% stenosis. In ORBIT II, OA treatment of lesions with ≥95% stenosis resulted in a high rate of procedural success. Although the 3-year revascularization rate was higher in the ≥95% stenosis group, it is not unexpected given the challenge of treating such complex lesions. The results of this analysis suggest that OA may be a reasonable treatment strategy for tight, severely calcified subtotal occlusions.