Peripheral Artery Disease in Vulnerable Patient Populations: Outcomes of Orbital Atherectomy in Native Americans Compared to Non-Native Americans. A Single-Center Experience in Rural Oklahoma.

BACKGROUND/PURPOSE: Although the incidence of peripheral artery disease (PAD) and amputations is higher in Native Americans (NA) than Caucasians, the study of revascularization NA is limited, resulting in their under representation in clinical studies. Orbital atherectomy (OA) is widely utilized for endovascular revascularization of significantly calcified peripheral arteries and has been shown to improve limb salvage rates. METHODS/MATERIALS: A cohort of 74 consecutive PAD subjects undergoing OA treatment was retrospectively analyzed via Kaplan Meier (KM) and Propensity Score Matched (PSM) analysis. RESULTS: A significant proportion of the subjects were NA (16.2%). Compared to the non-NA, the NA had higher numerical baseline rates of wounds, dialysis, chronic kidney disease (CKD), and critical limb ischemia, but were numerically less likely to smoke and had similar rates of diabetes. There were very high rates of severe calcification (100% vs. 87%) and pre-procedure diameter stenosis (99% vs. 95%) in both groups. The NA and non-NA had good angiographic outcomes, resulting in low rates of post-procedure residual diameter stenosis (10% vs. 11%). Lastly, KM analysis indicated high freedom from amputation in both groups at 1 year (89% vs. 95%), as well as in the PSM subjects (89% vs. 100%). CONCLUSIONS: Despite numerically higher rates of co-morbidities at baseline (e.g., CKD, dialysis, and presence of non-healing wounds), the NA underwent successful revascularization with OA, resulting in high freedom from amputation at 1-year. Given the small sample size of NA, these results may not be generalizable-thus, larger studies on NA are warranted.

Antithrombotic treatment tailoring and risk score evaluation in elderly patients diagnosed with an acute coronary syndrome.

Age is an important prognostic factor in the outcome of acute coronary syndromes (ACS). A substantial percentage of patients who experience ACS is more than 75 years old, and they represent the fastest-growing segment of the population treated in this setting. These patients present different patterns of responses to pharmacotherapy, namely, a higher ischemic and bleeding risk than do patients under 75 years of age. Our aim was to identify whether the currently available ACS ischemic and bleeding risk scores, which has been validated for the general population, may also apply to the elderly population. The second aim was to determine whether the elderly benefit more from a specific pharmacological regimen, keeping in mind the numerous molecules of antiplatelet and antithrombotic drugs, all validated in the general population. We concluded that the GRACE (Global Registry of Acute Coronary Events) risk score has been extensively validated in the elderly. However, the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) bleeding score has a moderate correlation with outcomes in the elderly. Until now, there have not been head-to-head scores that quantify the ischemic versus hemorrhagic risk or scores that use the same end point and timeline (e.g., ischemic death rate versus bleeding death rate at one month). We also recommend that the frailty score be considered or integrated into the current existing scores to better quantify the overall patient risk. With regard to medical treatment, based on the subgroup analysis, we identified the drugs that have the least adverse effects in the elderly while maintaining optimal efficacy.

Diagnostic modalities for the evaluation of anomalous left main coronary arteries.

Anomalous coronary arteries are rare and usually identified as an incidental finding during cardiac catheterization. The particular difficulty with cardiac catheterization techniques is not necessarily the presence of the anomalous coronary artery, but its anatomic course. Oftentimes, surgical intervention is necessary once these anomalies are discovered. The identification and anatomic characterization of anomalous coronary arteries has been significantly advanced with the use of current diagnostic noninvasive imaging modalities. We present 3 cases of an anomalous left main coronary artery that arises from the right sinus of Valsalva. Noninvasive imaging methods provided a clear anatomic course of the anomalous vessel.

Correlations between fractional flow reserve and intravascular ultrasound in patients with an ambiguous left main coronary artery stenosis.

BACKGROUND: Intravascular ultrasound (IVUS) is being used to assess the significance of a left main coronary artery stenosis (LMCS). However, the cutoff values of IVUS parameters at which to predict a fractional flow reserve (FFR) of 0.75 are unknown. METHODS AND RESULTS: In 55 patients with an angiographically ambiguous LMCS, a pressure guidewire was used to calculate FFR, and IVUS parameters were calculated after automatic pullback. FFR averaged 0.86+/-0.13 (range, 0.55 to 1.0). IVUS minimum lumen diameter (MLD), minimum lumen area (MLA), cross-sectional narrowing (CSN), and area stenosis (AS) were 3.8+/-0.61 mm, 7.65+/-2.9 mm2, 59+/-13%, and 47+/-19%, respectively. Regression analysis demonstrated strong correlations between FFR and MLD (r=0.79, P<0.0001) as well as between FFR and MLA (r=0.74, P<0.0001). There were inverse, moderate correlations between FFR and CSN (r=0.69, P<0.0001), followed by those between FFR and AS (r=0.54, P<0.0001). Compared with FFR as the "gold standard," an MLD of 2.8 mm had the highest sensitivity and specificity (93% and 98%, respectively) for determining the significance of an LMCS, followed by an MLA of 5.9 mm2 (93% and 95%, respectively). Based on an FFR <0.75 and an FFR > or =0.75, the 38-month survival and event-free survival estimates (EFSEs) were both 100% and 100% versus 90%, respectively (P=NS). CONCLUSIONS: We conclude that (1) an IVUS MLD and MLA of 2.8 mm and 5.9 mm2, respectively, strongly predict the physiological significance of an LMCS and (2) among patients with an LMCS, an FFR of 0.75 is a strong predictor of survival and EFSE.

Targeted disruption of the matrix metalloproteinase-9 gene impairs smooth muscle cell migration and geometrical arterial remodeling.

Matrix remodeling plays an important role in the physiological and pathological remodeling of blood vessels. We specifically investigated the role of matrix metalloproteinase (MMP)-9, an MMP induced during arterial remodeling, by assessing the effects of genetic MMP-9 deficiency on major parameters of arterial remodeling using the mouse carotid artery flow cessation model. Compared with remodeling of matched wild-type (WT) arteries, MMP-9 deficiency decreased intimal hyperplasia, reduced the late lumen loss, eliminated the correlation between intimal hyperplasia and geometric remodeling, and led to significant accumulation of interstitial collagen. Biochemical analysis of MMP-9 knockout (KO) arterial tissue and isolated smooth muscle cells (SMCs) confirmed the lack of MMP-9 expression or compensation by other gelatinases. To investigate potential mechanisms for the in vivo observations, we analyzed in vitro effects of MMP-9 deficiency on the migration, proliferation, and collagen gel contracting capacity of aortic SMCs isolated from MMP-9 KO and WT mice. Although proliferation was comparable, we found that MMP-9-deficient cells had not only decreased migratory activity, but they also had decreased capacity to contract collagen compared with WT cells. Thus, MMP-9 appears to be involved not only in degradation, but also in reorganization of a collagenous matrix, both facets being essential for the outcome of arterial remodeling. Our results also establish MMP-9 as an attractive therapeutic target for limiting the effects of pathological arterial remodeling in restenosis and atherosclerosis.

Expansive arterial remodeling is associated with increased neointimal macrophage foam cell content: the murine model of macrophage-rich carotid artery lesions.

BACKGROUND: Recent observations associate plaque instability with expansive arterial remodeling, suggesting a common driving mechanism. METHODS AND RESULTS: To demonstrate that macrophages, a characteristic of vulnerable plaques, also assist in expansive remodeling, we compared carotid artery remodeling due to formation of experimental macrophage-rich and macrophage-poor lesions in the flow cessation model in hypercholesterolemic apolipoprotein E knockout (ApoE KO) and wild type (WT) mice. After ligation, macrophages started to rapidly accumulate in ApoE KO but not in WT carotid artery lesions. Macrophage-rich ApoE KO intimal lesions grew fast, typically occluding within 14 days, despite a tripling of the vessel area. Outward remodeling of macrophage-rich ApoE KO arteries positively correlated with macrophage area (r2=0.600, P<0.001). To investigate potential mechanisms of macrophage-enabled expansive remodeling, we compared levels of matrix metalloproteinases in homogenates of macrophage-rich and macrophage-poor carotid arteries. Gelatinolytic activity of macrophage-rich lesions increased faster and reached maximal levels several fold higher than in the macrophage-poor WT lesions. CONCLUSIONS: Our results suggest that macrophages facilitate expansive arterial remodeling through increased matrix degradation by matrix metalloproteinases. This initially favorable remodeling action may eventually increase the vulnerability of macrophage-rich atherosclerotic plaques.