Faculty Bibliography

OBJECTIVE: Patients in the Carotid Revascularization Endarterectomy vs Stenting Trial (CREST) had duplex ultrasound (DU) scans prior to treatment and during follow-up to document the severity of carotid disease and the anatomic outcome of carotid endarterectomy (CEA) or carotid artery stenting (CAS). An ultrasound core laboratory (UCL) reviewed DU data from the clinical sites. This analysis was done to determine the agreement between site-reported and UCL-verified DU velocity measurements. METHODS: Clinical site DU worksheets, B-mode images, and Doppler velocity waveforms for the treated carotid arteries were reviewed at the UCL. The highest internal carotid artery peak systolic velocity (PSV) and associated Doppler angle were verified. If the angle was misaligned by >3 degrees, it was remeasured at the UCL and the PSV was recalculated. Agreement for PSV was defined as site-reported PSV within +/-5% of UCL-verified PSV. Transcription errors were corrected by the UCL but were not considered as disagreements. Follow-up analysis was limited to patients who received the assigned treatment. RESULTS: The UCL reviewed 1702 prior-to-treatment and 1743 12-month follow-up DU scans (873 CEA, 870 CAS) from 111 clinical sites. Site-reported and UCL-verified PSV agreed in 1124 (66%) of the prior-to-treatment scans and 1200 (69%) of the follow-up scans. In those cases with a disagreement, Doppler angle accounted for disagreement in 339 (59%) of the prior-to-treatment scans and 277 (51%) of the follow-up scans. Based on a threshold PSV for >/=70% stenosis of >/=230 cm/s on the prior-to-treatment scans and >/=300 cm/s on the follow-up scans, UCL review resulted in reclassification of stenosis severity in 75 (4.4%) of the prior-to-treatment scans and 13 (0.75%) of the follow-up scans. There is evidence that the proportion of reclassification at follow-up was greater for CAS (10 scans; 1.2%) than for CEA (three scans; 0.34%) (P = .057). CONCLUSIONS: There was a high rate of agreement between site-reported and UCL-verified DU results in CREST, and UCL review was associated with a low rate of stenosis reclassification. However, angle alignment errors were quite common and prompted recalculation of velocity in 20% of prior-to-treatment scans and 18% of follow-up scans. The use of a UCL provides a uniform process for DU interpretation and can identify sources of error and suggest technical improvements for future studies.

OBJECTIVES: To evaluate the 9-month safety and effectiveness outcomes of the Formula balloon-expandable renal stent (Cook Medical, Bloomington, IN) for the treatment of atherosclerotic renal artery stenosis (RAS) following suboptimal angioplasty. BACKGROUND: Atherosclerotic RAS can cause hypertension and ischemic nephropathy. When clinically indicated, an interventional approach with renal angioplasty and stent implantation is the preferred method for revascularization of atherosclerotic renal artery stenoses. METHODS: The REFORM study is a prospective, multicenter, single-arm study of stent implantation following suboptimal PTRA using the Formula stent. One hundred patients with atherosclerotic ostial renal artery lesions =18 mm in length with a >50% residual stenosis following PTA were enrolled. The primary endpoint was 9-month primary patency. RESULTS: The 9-month primary patency rate was 91.7%. The 9-month major adverse event rate was 2.2%. Mean systolic blood pressure was significantly decreased at follow-up (from 150 +/- 21 mm Hg at baseline to 141 +/- 21 mm Hg at 9 months; P = 0.003). Mean serum creatinine (SCr) level and mean estimated glomerular filtration rate (eGFR) were not significantly different at 9 months. A clinically meaningful improvement in renal function (i.e., =25% increase in eGFR or =0.5 mg/dl decrease in SCr) was observed in 9% of patients at 1 month and 12% of patients at 9 months. A clinically meaningful decline in renal function (i.e., =25% decrease in eGFR or =0.5 mg/dl increase in SCr) was observed in only 3% of patients at 1 month and 7% of patients at 9 months. CONCLUSIONS: The Formula stent was safe and effective in treating atherosclerotic RAS following suboptimal angioplasty.

PURPOSE OF REVIEW: Carotid endarterectomy (CEA) has been shown to prevent stroke in patients with severe carotid stenosis. Carotid artery stenting (CAS) has emerged as a less invasive alternative technique. Data regarding comparative effectiveness of CAS and CEA are now available and merit review. RECENT FINDINGS: Four large randomized controlled trials (RCTs) comparing CAS and CEA have shown a higher rate of stroke in symptomatic patients. The largest and most recent trial reported a lower occurrence of myocardial infarction (MI) following CAS and showed overall comparability of CAS to CEA for both symptomatic and asymptomatic patients. Despite methodological differences, these RCTs are consistent in finding an interaction of patient age with outcomes. In younger patients, CAS appears equivalent or superior to CEA if considering the sum of death, stroke, and MI. In elderly patients, CEA appears to have a lower complication rate. For asymptomatic patients, reduction in event rates with current medical therapy may render previous trial results invalid. SUMMARY: CAS is an alternative to CEA in patients requiring carotid intervention. Comparison of both CAS and CEA with contemporary medical management will also be required before recommendations can be made regarding the optimal treatment of patients with asymptomatic carotid stenoses.

BACKGROUND: In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), the composite primary endpoint of stroke, myocardial infarction, or death during the periprocedural period or ipsilateral stroke thereafter did not differ between carotid artery stenting and carotid endarterectomy for symptomatic or asymptomatic carotid stenosis. A secondary aim of this randomised trial was to compare the composite endpoint of restenosis or occlusion. METHODS: Patients with stenosis of the carotid artery who were asymptomatic or had had a transient ischaemic attack, amaurosis fugax, or a minor stroke were eligible for CREST and were enrolled at 117 clinical centres in the USA and Canada between Dec 21, 2000, and July 18, 2008. In this secondary analysis, the main endpoint was a composite of restenosis or occlusion at 2 years. Restenosis and occlusion were assessed by duplex ultrasonography at 1, 6, 12, 24, and 48 months and were defined as a reduction in diameter of the target artery of at least 70%, diagnosed by a peak systolic velocity of at least 3.0 m/s. Studies were done in CREST-certified laboratories and interpreted at the Ultrasound Core Laboratory (University of Washington). The frequency of restenosis was calculated by Kaplan-Meier survival estimates and was compared during a 2-year follow-up period. We used proportional hazards models to assess the association between baseline characteristics and risk of restenosis. Analyses were per protocol. CREST is registered with ClinicalTrials.gov, number NCT00004732. FINDINGS: 2191 patients received their assigned treatment within 30 days of randomisation and had eligible ultrasonography (1086 who had carotid artery stenting, 1105 who had carotid endarterectomy). In 2 years, 58 patients who underwent carotid artery stenting (Kaplan-Meier rate 6.0%) and 62 who had carotid endarterectomy (6.3%) had restenosis or occlusion (hazard ratio [HR] 0.90, 95% CI 0.63-1.29; p=0.58). Female sex (1.79, 1.25-2.56), diabetes (2.31, 1.61-3.31), and dyslipidaemia (2.07, 1.01-4.26) were independent predictors of restenosis or occlusion after the two procedures. Smoking predicted an increased rate of restenosis after carotid endarterectomy (2.26, 1.34-3.77) but not after carotid artery stenting (0.77, 0.41-1.42). INTERPRETATION: Restenosis and occlusion were infrequent and rates were similar up to 2 years after carotid endarterectomy and carotid artery stenting. Subsets of patients could benefit from early and frequent monitoring after revascularisation. FUNDING: National Institute of Neurological Disorders and Stroke and Abbott Vascular Solutions.

BACKGROUND AND PURPOSE: High stroke event rates among carotid artery stenting (CAS)-treated patients in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST) lead-in registry generated an a priori hypothesis that age may modify the relative efficacy of CAS versus carotid endarterectomy (CEA). In the primary CREST report, we previously noted significant effect modification by age. Here we extend this investigation by examining the relative efficacy of the components of the primary end point, the treatment-specific impact of age, and contributors to the increasing risk in CAS-treated patients at older ages. METHODS: Among 2502 CREST patients with high-grade carotid stenosis, proportional hazards models were used to examine the impact of age on the CAS-to-CEA relative efficacy, and the impact of age on risk within CAS-treated and CEA-treated patients. RESULTS: Age acted as a treatment effect modifier for the primary end point (P interaction=0.02), with the efficacy of CAS and CEA approximately equal at age 70 years. For CAS, risk for the primary end point increased with age (P<0.0001) by 1.77-times (95% confidence interval, 1.38-2.28) per 10-year increment; however, there was no evidence of increased risk for CEA-treated patients (P=0.27). Stroke events were the primary contributor to the overall effect modification (P interaction=0.033), with equal risk at approximately 64 years. The treatment-by-age interaction for CAS and CEA was not altered by symptomatic status (P=0.96) or by sex (P=0.45). CONCLUSIONS: Outcomes after CAS versus CEA were related to patient age, attributable to increasing risk for stroke after CAS at older ages. Patient age should be an important consideration when choosing between the 2 procedures for treating carotid stenosis. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732.

OBJECTIVES: The purpose of this study was to evaluate the feasibility and efficacy of the percutaneous device closure of a consecutive series of patients with periprosthetic paravalvular leaks referred to our structural heart disease center with congestive heart failure and hemolytic anemia. BACKGROUND: Clinically significant periprosthetic paravalvular leak is an uncommon but serious complication after surgical valve replacement. Percutaneous closure has been utilized as an alternative to surgical repair of this defect in high-risk surgical patients. METHODS: This is a retrospective review of 57 percutaneous paravalvular leak closures that were performed in 43 patients (67% male, mean age 69.4 +/- 11.7 years) between April 2006 and September 2010. Integrated imaging modalities were used for the evaluation, planning, and guidance of the interventions. RESULTS: Closure was successful in 86% of leaks and in 86% of patients. Twenty-eight of 35 patients improved by at least 1 New York Heart Association functional class. The percentage of patients requiring blood transfusions and/or erythropoietin injections post-procedure decreased from 56% to 5%. Clinical success was achieved in 89% of the patients in whom procedure was successful. The survival rates for patients at 6, 12, and 18 months after paravalvular leak closures were 91.9%, 89.2%, and 86.5%, respectively. Freedom from cardiac-related death at 42 months post-procedure was 91.9%. CONCLUSIONS: Percutaneous closure of symptomatic paravalvular leaks, facilitated by integrated imaging modalities has a high rate of acute and long-term success and appears to be effective in managing symptoms of heart failure and hemolytic anemia.

OBJECTIVES: The goal was to compare stent sizing by coronary computed tomographic angiography (CCTA) with that deployed in an experienced setting based upon conventional coronary angiography (CA). BACKGROUND: Stent sizing is currently performed by visual estimation, with infrequent guidance by intravascular ultrasound. CCTA permits quantitative determination of stent length (Stent L) and diameter (Stent D). METHODS: Projected L (CTA-Stent L) and D (CTA-Stent D) were determined from CCTA obtained in 248 patients with 352 lesions undergoing percutaneous coronary intervention within 4 months of the CCTA, and were compared to the Stent-L and Stent-D of the actually deployed stents. The effects of lesion modification and calcified plaque were also evaluated. RESULTS: There were significant correlations between CTA-Stent L and Stent L (r = 0.656, P < 0.0001) and between CTA-Stent D and Stent D (r = 0.40, P < 0.001). Median predicted CTA-Stent L was slightly longer (20 mm vs. 18 mm, P < 0.0001) and predicted CTA-Stent D was slightly smaller (3.0 mm vs. 3.2 mm, P < 0.0001) than Stent-L and Stent-D, respectively. The differences were unchanged in stents with lesion modification by pre-dilation or intracoronary nitroglycerin. CTA Stent-L and CTA Stent-D increased significantly with increasing calcium (P < 0.0001 and P = 0.019, respectively). CONCLUSIONS: (1) There are significant correlations between CCTA and CA based stent sizing in an experienced setting. (2) CCTA projects slightly longer and slightly smaller diameter stents than those deployed during PCI irrespective of lesion modification; the small differences are unlikely to have clinical significance. (3) CCTA may offer a noninvasive alternative to intravascular ultrasound for stent planning.

OBJECTIVES: The purpose of this study was to compare health-related quality of life (HRQOL) outcomes in patients treated with carotid artery stenting (CAS) versus carotid endarterectomy (CEA). BACKGROUND: In CREST (Carotid Revascularization Endarterectomy versus Stenting Trial), the largest randomized trial of carotid revascularization to date, there was no significant difference in the primary composite endpoint, but rates of stroke and myocardial infarction (MI) differed between CAS and CEA. To help guide individualized clinical decision making, we compared HRQOL among patients enrolled in the CREST study. We also performed exploratory analyses to evaluate the association between periprocedural complications and HRQOL. METHODS: We measured HRQOL at baseline, and after 2 weeks, 1 month, and 1 year among 2,502 patients randomly assigned to either CAS or CEA in the CREST study. The HRQOL was assessed using the Medical Outcomes Study Short-Form 36 (SF-36) and 6 disease-specific scales designed to study HRQOL in patients undergoing carotid revascularization. RESULTS: At both 2 weeks and 1 month, CAS patients had better outcomes for multiple components of the SF-36, with large differences for role physical function, pain, and the physical component summary scale (all p < 0.01). On the disease-specific scales, CAS patients reported less difficulty with driving, eating/swallowing, neck pain, and headaches but more difficulty with walking and leg pain (all p < 0.05). However, by 1 year, there were no differences in any HRQOL measure between CAS and CEA. In the exploratory analyses, periprocedural stroke was associated with poorer 1-year HRQOL across all SF-36 domains, but periprocedural MI or cranial nerve palsy were not. CONCLUSIONS: Among patients undergoing carotid revascularization, CAS is associated with better HRQOL during the early recovery period as compared with CEA-particularly with regard to physical limitations and pain-but these differences diminish over time and are not evident after 1 year. Although CAS and CEA are associated with similar overall HRQOL at 1 year, event-specific analyses confirm that stroke has a greater and more sustained impact on HRQOL than MI. (Carotid Revascularization Endarterectomy versus Stenting Trial [CREST]; NCT00004732)

BACKGROUND: Sustained benefits of drug-eluting stents in femoropopliteal arteries have not been demonstrated. This prospective, multinational, randomized study was designed to compare the 12-month safety and effectiveness of a polymer-free, paclitaxel-coated nitinol drug-eluting stent (DES) with percutaneous transluminal angioplasty (PTA) and provisional bare metal stent (BMS) placement in patients with femoropopliteal peripheral artery disease. METHODS AND RESULTS: Patients were randomly assigned to primary DES implantation (n=236) or PTA (n=238). Demographics and lesion characteristics were similar between groups (eg, average lesion length, approximately 65+/-40 mm). One hundred twenty patients had acute PTA failure and underwent secondary random assignment to provisional DES (n=61) or BMS (n=59). Primary end points were the 12-month rates of event-free survival and patency in the primary DES and PTA groups. Compared with the PTA group, the primary DES group exhibited superior 12-month event-free survival (90.4% versus 82.6%; P=0.004) and primary patency (83.1% versus 32.8%; P<0.001), satisfying the primary hypotheses. In the secondary evaluations, (1) the primary DES group exhibited superior clinical benefit compared with the PTA group (88.3% versus 75.8%; P<0.001), (2) the provisional DES group exhibited superior primary patency (89.9% versus 73.0%; P=0.01) and superior clinical benefit (90.5% and 72.3%, P=0.009) compared with the provisional BMS group, and (3) the stent fracture rate (both DES and BMS) was 0.9% (4/457). CONCLUSIONS: Femoropopliteal peripheral artery disease treatment with the paclitaxel-eluting stent was associated with superior 12-month outcomes compared with PTA and provisional BMS placement.