A comprehensive simulation framework for predicting the eCLIPs implant crimping into a catheter and its deployment mechanisms.

Tubular flow diverters (FDs) represent an important subset of the endovascular treatment of cerebral aneurysms (CAs), acting to reduce aneurysm inflow, eventually resulting in aneurysm thrombosis and occlusion. eCLIPs (product of Evasc Neurovascular Enterprises, Vancouver, Canada), an innovative non-tubular implant causes flow diversion by bridging the neck of bifurcation CAs. However, in a small subset of challenging bifurcation aneurysms with fusiform pathology, the currently available eCLIPs models do not provide sufficient neck bridging resulting in a gap created between the device structure and the aneurysm/artery wall. To overcome this challenge, a new design of the eCLIPs (VR-eCLIPs) was developed by varying the rib length to cover such an inflow gap. To optimize the new product development process, and avoiding expensive and time-consuming iterative manufacture of prototype devices, we have developed a new finite element model to simulate the crimping and expansion processes of the VR-eCLIPs implant, and assess the possibility of plastic deformation. Results indicated that neither eCLIPs nor VR-eCLIPs experience plastic deformation during the crimping process. Upon full expansion, the ribs of VR-eCLIPs interact with the aneurysm and artery wall to cover the inflow gap that exists in certain challenging anatomies. This process serves as a basis to expedite design development prior to prototype manufacturing.

Physiological remodeling of bifurcation aneurysms: preclinical results of the eCLIPs device.

OBJECTIVE Intracranial bifurcation aneurysms are complex lesions for which current therapy, including simple coiling, balloon- or stent-assisted coiling, coil retention, or intrasaccular devices, is inadequate. Thromboembolic complications due to a large burden of intraluminal metal, impedance of access to side branches, and a high recurrence rate, due largely to the unmitigated high-pressure flow into the aneurysm (water hammer effect), are among the limitations imposed by current therapy. The authors describe herein a novel device, eCLIPs, and its use in a preclinical laboratory study that suggests the device's design and functional features may overcome many of these limitations. METHODS A preclinical model of wide-necked bifurcation aneurysms in rabbits was used to assess functional features and efficacy of aneurysm occlusion by the eCLIPs device. RESULTS The eCLIPs device, in bridging the aneurysm neck, allows coil retention, disrupts flow away from the aneurysm, leaves the main vessel and side branches unencumbered by intraluminal metal, and serves as a platform for endothelial growth across the neck, excluding the aneurysm from the circulation. CONCLUSIONS The eCLIPs device permits physiological remodeling of the bifurcation.

Role of preliminary registry data in development of a clinical trial for an innovative device: a small but integral piece of a health policy initiative.

Establishing a national health policy at a macro level involves the integration of a series of health initiatives across a spectrum of activities, including clinical care. Evaluation of the safety and efficacy of a new medical device ultimately evolves to testing in humans. The pathway to a formal prospective clinical trial includes a stepwise appreciation of pre-clinical data and detailed analysis of data obtained from preliminary registries, where information about appropriate patient selection and use of the device is obtained. Evaluation of procedural and follow-up efficacy and safety data in a preliminary series of cases, chosen to simulate published data, allows the design and conduct of clinical trials that are required to verify preliminary observations, closing the loop on one aspect of modifying health policy decisions.

A training paradigm to enhance performance and safe use of an innovative neuroendovascular device.

Training has been important to facilitate the safe use of new devices designed to repair vascular structures. This paper outlines the generic elements of a training program for vascular devices and uses as an example the actual training requirements for a novel device developed for the treatment of bifurcation intracranial aneurysms. Critical elements of the program include awareness of the clinical problem, technical features of device, case selection, and use of a simulator. Formal proctoring, evaluation of the training, and recording the clinical outcomes complement these elements. Interventional physicians should embrace the merits of a training module to improve the user experience, and vendors, physicians, and patients alike should be aligned in the goal of device training to improve its success rate and minimize complications of the procedure.

Spontaneous coronary artery dissection: association with predisposing arteriopathies and precipitating stressors and cardiovascular outcomes.

BACKGROUND: Nonatherosclerotic spontaneous coronary artery dissection (NA-SCAD) is underdiagnosed and an important cause of myocardial infarction in young women. The frequency of predisposing and precipitating conditions and cardiovascular outcomes remains poorly described. METHODS AND RESULTS: Patients with NA-SCAD prospectively evaluated (retrospectively or prospectively identified) at Vancouver General Hospital were included. Angiographic SCAD diagnosis was confirmed by 2 experienced interventional cardiologists and categorized as type 1 (multiple lumen), 2 (diffuse stenosis), or 3 (mimic atherosclerosis). Fibromuscular dysplasia screening of renal, iliac, and cerebrovascular arteries were performed with angiography or computed tomographic angiography/MR angiography. Baseline, predisposing and precipitating conditions, angiographic, revascularization, in-hospital, and long-term events were recorded. We prospectively evaluated 168 patients with NA-SCAD. Average age was 52.1±9.2 years, 92.3% were women (62.3% postmenopausal). All presented with myocardial infarction. ECG showed ST-segment elevation in 26.1%, and 3.6% had ventricular tachycardia/ventricular fibrillation arrest. Fibromuscular dysplasia was diagnosed in 72.0%. Precipitating emotional or physical stress was reported in 56.5%. Majority had type 2 angiographic SCAD (67.0%), only 29.1% had type 1, and 3.9% had type 3. The majority (134/168) were initially treated conservatively. Overall, 6 of 168 patients had coronary artery bypass surgery and 33 of 168 had percutaneous coronary intervention in-hospital. Of those treated conservatively (n=134), 3 required revascularization for SCAD extension, and all 79 who had repeat angiogram ≥26 days later had spontaneous healing. Two-year major adverse cardiac events were 16.9% (retrospectively identified group) and 10.4% (prospectively identified group). Recurrent SCAD occurred in 13.1%. CONCLUSIONS: Majority of patients with NA-SCAD had fibromuscular dysplasia and type 2 angiographic SCAD. Conservative therapy was associated with spontaneous healing. NA-SCAD survivors are at risk for recurrent cardiovascular events, including recurrent SCAD.

Nonatherosclerotic coronary artery disease in young women.

BACKGROUND: Nonatherosclerotic coronary artery disease (NACAD) is an important cause of myocardial infarction (MI) in young women but is often missed on coronary angiography, especially spontaneous coronary artery dissection (SCAD). The prevalence of NACAD in young women has not been described. METHODS: We retrospectively reviewed all coronary angiograms of women aged 50 years and younger at Vancouver General Hospital from December 1, 2009 to November 30, 2011. The angiograms were reviewed by 2 experienced interventional cardiologists, and reported as normal (<30% stenosis), atherosclerotic coronary artery disease (ACAD), or NACAD. NACAD was further characterized as SCAD, coronary fibromuscular dysplasia (FMD), ectasia, vasculitis, embolism, congenital anomaly, or unclear etiology. RESULTS: Of 7605 coronary angiograms performed, 177 were done in women aged 50 years and younger. The mean age was 45.4 ± 4.9 (range, 31-50) years, 76 of 177 (42.9%) presented with acute coronary syndrome, and 66 were troponin-positive. Ninety-seven (54.8%) women had normal arteries, 54 (30.5%) had ACAD, 23 (13.0%) had NACAD, and 3 (1.7%) had unclear etiology. Of those with NACAD, SCAD was observed in 16 (all troponin-positive and 13 of 16 had noncoronary FMD), and 2 had irregular beading suspicious of coronary FMD. Coronary vasculitis was suspected in 2, and 5 had coronary ectasia. Among women with MI (66/177), 19 (28.8%) had normal arteries (3 Takotsubo cardiomyopathy), 24 (36.4%) had ACAD, 20 (30.3%) had NACAD, 16 (24.2%) had SCAD, and 3 had unclear etiology. CONCLUSIONS: NACAD was not rare among young women (aged 50 years and younger) undergoing coronary angiography and was an important cause of MI, accounting for 30%. SCAD was the most commonly encountered NACAD in young women, causing 24% of MIs.

Spontaneous coronary artery dissection: prevalence of predisposing conditions including fibromuscular dysplasia in a tertiary center cohort.

OBJECTIVES: We sought to evaluate the prevalence of fibromuscular dysplasia (FMD) and other predisposing conditions among spontaneous coronary artery dissection (SCAD) patients. BACKGROUND: Spontaneous coronary artery dissection is considered rare. However, we observed many young women with SCAD and concomitant FMD. METHODS: Spontaneous coronary artery dissection patients were identified prospectively and retrospectively at Vancouver General Hospital over the past 6 years. Coronary angiograms were meticulously reviewed by 2 senior interventional cardiologists. Identified patients were contacted for prospective evaluation at our SCAD clinic, and screening for FMD of renal, iliac, and cerebrovascular arteries was performed with computed tomography angiography or magnetic resonance angiography, if not already screened during the index angiogram. Potential predisposing and precipitating conditions for SCAD were extracted from clinical history. RESULTS: We identified 50 patients with nonatherosclerotic SCAD from April 2006 to March 2012. Average age was 51.0 years, and almost all were women (98.0%). All presented with myocardial infarction (MI), 30.0% had ST-segment elevation, and 70.0% had non-ST-segment elevation MI. Only 1 was postpartum, and 2 were involved in intense isometric exercises. Emotional stress was reported in 26.0% before the MI. Twelve percent had >1 dissected coronary artery. Most SCAD patients had FMD of ≥1 noncoronary territory (86.0%): 25 of 43 (58.1%) renal, 21 of 43 (48.8%) iliac, and 20 of 43 (46.5%) cerebrovascular (6 of 43, 14.0% had intracranial aneurysm). Five had incomplete FMD screening. CONCLUSIONS: Nonatherosclerotic SCAD predominantly affects women, and most have concomitant FMD. We suspect these patients have underlying coronary FMD that predisposed them to SCAD, but this requires proof from histology or intracoronary imaging of the affected coronary arteries.

Perforation during stenting of a coronary artery with morphologic changes of fibromuscular dysplasia: an unrecognized risk with percutaneous intervention.

Fibromuscular dysplasia (FMD) is increasingly recognized as a nonatherosclerotic pathology in young women presenting with acute coronary syndromes. The angiographic appearance of these lesions may mimic typical atherosclerosis, and a high index of suspicion is needed. The pathophysiological changes in the intima and media alter the vessel's elasticity and may adversely affect the lesion's response to balloon dilatation and stenting. Intracoronary imaging is therefore useful when planning percutaneous intervention. We present a case of stent implantation in a coronary FMD lesion complicated by perforation with intravascular ultrasound images demonstrating the typical changes of FMD.

Abbreviated infusion of eptifibatide after successful coronary intervention The BRIEF-PCI (Brief Infusion of Eptifibatide Following Percutaneous Coronary Intervention) randomized trial.

OBJECTIVES: The purpose of this study was to assess whether the early discontinuation of eptifibatide infusion in nonemergent percutaneous coronary intervention (PCI) is associated with a higher frequency of periprocedural ischemic myonecrosis. BACKGROUND: The recommended regimen for eptifibatide is a double bolus followed by an infusion for 18 h. It is not known whether the infusion can be shortened if the PCI is uncomplicated. METHODS: We enrolled 624 patients with stable angina, acute coronary syndrome, or recent ST-segment elevation myocardial infarction (>48 h) who underwent successful coronary stenting and received eptifibatide. Patients were randomly assigned to receive either an 18-h infusion or an abbreviated infusion of <2 h. The primary end point was the incidence of periprocedural myonecrosis defined as troponin-I elevation >0.26 microg/l. Secondary end points included death, myocardial infarction, urgent target vessel revascularization at 30 days, and in-hospital major bleeding using the REPLACE-2 (Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events) trial criteria. RESULTS: The incidence of periprocedural myonecrosis was 30.1% in the <2-h group versus 28.3% in the 18-h group (mean difference: 1.8%; upper bound of 95% confidence interval: 7.8%; p < 0.012 for noninferiority). The 30-day incidence of myocardial infarction, death, and target vessel revascularization was similar in both groups (p = NS). Major bleeding was less frequent in the <2-h group (1.0% vs. 4.2%, p = 0.02). CONCLUSIONS: After uncomplicated PCI, eptifibatide infusion can be abbreviated safely to <2 h. It is not inferior to the standard 18-h infusion in preventing ischemic outcome, and it may be associated with less major bleeding. (Brief Infusion of Eptifibatide Following Percutaneous Coronary Intervention [BRIEF PCI]; NCT00111566).

A novel endovascular clip system for the treatment of intracranial aneurysms: technology, concept, and initial experimental results. Laboratory investigation.

OBJECT: The authors describe a novel device for the endovascular treatment of intracranial aneurysms, the endovascular clip system (eCLIPs). Descriptions of the device and its delivery system as well as the results of flow model tests and the treatment of experimental aneurysms are provided. METHODS: The eCLIPs comprises a flexible hybrid implantable device (an anchor and a covered leaf) and a balloon catheter delivery system, designed to be positioned and activated in the parent vessel in such a way that the covered portion will abut the aneurysm neck. The eCLIPs was subjected to testing in glass, elastomeric, and cadaveric flow models to determine its navigability, orientation, and activation compared with commercially available stents. In a second experiment, 8 carotid artery sidewall aneurysms in swine were treated using eCLIPs. The degree of occlusion was observed on angiography immediately following and 30 days after device activation, and a histological analysis was performed at 30 days. RESULTS: The device could navigate tortuous glass models and human cadaveric vessels. Compared with commercially available stents, the eCLIPs performed well. It could be navigated, oriented, and activated easily and reliably. With regard to the 8 porcine experimental aneurysms, immediate postactivation angiograms confirmed complete occlusion of 4 lesions and near occlusion of the other 4. Angiographic follow-up at 30 days postactivation showed occlusion of all 8 aneurysms and patency of all parent vessels. Histopathological analysis revealed aneurysm healing, with smooth-muscle cells growing across the lesion neck to allow reendothelialization. CONCLUSIONS: Aneurysm occlusion with a single extrasaccular endovascular device has potential advantages. The authors believe that eCLIPs may prove to be a useful tool in the endovascular treatment of cerebral aneurysms. The system should reduce risks associated with coiling, procedure time, costs, and radiation exposure. The device satisfactorily occluded 8 experimental sidewall aneurysms. The observed healing pattern is similar to that seen after microsurgical clipping.

The effects of aspirin and clopidogrel response on myonecrosis after percutaneous coronary intervention: a BRIEF-PCI (Brief Infusion of Intravenous Eptifibatide Following Successful Percutaneous Coronary Intervention) trial substudy.

OBJECTIVES: The purpose of this study was to evaluate the effects of aspirin and clopidogrel response on myonecrosis after percutaneous coronary intervention (PCI) with glycoprotein (GP) IIb/IIIa blockade. BACKGROUND: Aspirin and clopidogrel resistance is increasingly recognized, but its effects on PCI outcomes with GP IIb/IIIa blockade are unknown. METHODS: This was a prospective, pre-specified substudy of the BRIEF-PCI (Brief Infusion of Intravenous Eptifibatide Following Successful Percutaneous Coronary Intervention) trial, which randomized 624 patients to 18-h or <2-h eptifibatide infusion after uncomplicated PCI. To be eligible, patients must have been pre-treated with aspirin (>or=5 days) and clopidogrel (75 mg/day >or=5 days, 300 mg loading >or=6 h, or 600 mg loading >or=2 h) and must not have received GP IIb/IIIa inhibitors within 48 h. Verify-Now Aspirin and Clopidogrel (P2Y(12)) assays were performed at baseline before PCI. Patients with aspirin reaction unit (ARU) >or=550 were labeled as aspirin resistant. Clopidogrel low-responders were defined as those in the lowest quartile of platelet inhibition. The primary end point was the prevalence of myonecrosis within 24 h after PCI. RESULTS: We enrolled 209 patients into our substudy, of which 185 had aspirin response assessed, 198 had clopidogrel response assessed, and 174 had both assessed. There were 4.9% who were aspirin resistant. Clopidogrel low-responders were defined as those in the lowest quartile with platelet inhibition <19%. Only 1.1% had both aspirin resistance and low clopidogrel response. There was no difference in myonecrosis prevalence among aspirin-resistant compared with aspirin-sensitive patients (11.1% vs. 27.8%, p = 0.259) or among clopidogrel low-responders compared with clopidogrel responders (23.5% vs. 29.3%, p = 0.433). CONCLUSIONS: Aspirin and clopidogrel response did not affect myonecrosis prevalence amongst patients who received eptifibatide for PCI.

Percutaneous transarterial aortic valve replacement in selected high-risk patients with aortic stenosis.

BACKGROUND: Percutaneous aortic valve replacement represents an endovascular alternative to conventional open heart surgery without the need for sternotomy, aortotomy, or cardiopulmonary bypass. METHODS AND RESULTS: Transcatheter implantation of a balloon-expandable stent valve using a femoral arterial approach was attempted in 50 symptomatic patients with severe aortic stenosis in whom there was a consensus that the risks of conventional open heart surgery were very high. Valve implantation was successful in 86% of patients. Intraprocedural mortality was 2%. Discharge home occurred at a median of 5 days (interquartile range, 4 to 13). Mortality at 30 days was 12% in patients in whom the logistic European System for Cardiac Operative Risk Evaluation risk score was 28%. With experience, procedural success increased from 76% in the first 25 patients to 96% in the second 25 (P=0.10), and 30-day mortality fell from 16% to 8% (P=0.67). Successful valve replacement was associated with an increase in echocardiographic valve area from 0.6+/-0.2 to 1.7+/-0.4 cm2. Mild paravalvular regurgitation was common but was well tolerated. After valve insertion, there was a significant improvement in left ventricular ejection fraction (P<0.0001), mitral regurgitation (P=0.01), and functional class (P<0.0001). Improvement was maintained at 1 year. Structural valve deterioration was not observed with a median follow-up of 359 days. CONCLUSIONS: Percutaneous valve replacement may be an alternative to conventional open heart surgery in selected high-risk patients with severe symptomatic aortic stenosis.

Redefining the normal angiogram using population-derived ranges for coronary size and shape: validation using intravascular ultrasound and applications in diverse patient cohorts.

OBJECTIVES: To develop a method for quantitating coronary angiographic abnormalities of segmental size and shape (tapering) in comparison to gender- and segment-specific, population derived, normal values. BACKGROUND: In the absence of obvious focal stenoses, remodeling renders the angiogram insensitive to the presence of atherosclerosis and invalidates use of a "normal reference segment" for calculation of percent diameter stenosis. METHODS: Equations were created for detection of size/shape abnormalities of coronary angiographic segments. After validation using intravascular ultrasound (IVUS), the equations were applied to a cohort of segments judged to be completely normal by a panel of highly experienced, core laboratory technicians; and a cohort of patients judged by an experienced interventionalist to have completely normal coronaries. RESULTS: In patients assessed by core technicians, 53% (162/303) of males, 39% (209/538) of normal segments in males, 60% (56/94) of females, and 40% (81/205) of normal segments in females had quantifiable abnormalities. In patients with normal coronaries as judged by an experienced interventionalist, 100% of males (n = 14) and females (n = 19), 37% (67/182) of segments in males and 43% (105/247) of segments in females had abnormalities. The left main segment was most commonly abnormal. CONCLUSIONS: We propose a set of equations validated using IVUS and based on gender- and segment-specific normal values for coronary angiographic size and shape that markedly improves the sensitivity of the coronary angiogram for detection of abnormalities. The method should replace the unfounded practice of labeling coronary angiograms as "normal" based solely on the failure to detect focal stenoses.

Percutaneous aortic valve implantation: a case report.

The present case demonstrates the percutaneous implantation of a bioprosthetic valve in a patient with severe aortic stenosis. An 85-year-old man with significant comorbidities was determined to be at unacceptable risk with traditional surgical valve replacement. Percutaneous aortic valve implantation was performed, was successful and uncomplicated, with significant clinical and hemodynamic improvement. Currently, this procedure is an option only for symptomatic patients who are not appropriate candidates for surgical valve replacement.

Percutaneous aortic valve implantation retrograde from the femoral artery.

BACKGROUND: Percutaneous aortic valve implantation by an antegrade transvenous approach has been described but is problematic. Retrograde prosthetic aortic valve implantation via the femoral artery has potential advantages. Percutaneous prosthetic aortic valve implantation via the femoral arterial approach is described and the initial experience reported. METHODS AND RESULTS: The valve prosthesis is constructed from a stainless steel stent with an attached trileaflet equine pericardial valve and a fabric cuff. After routine aortic balloon valvuloplasty, a 22F or 24F sheath is advanced from the femoral artery to the aorta. A steerable, deflectable catheter facilitates manipulation of the prosthesis around the aortic arch and through the stenotic valve. Rapid ventricular pacing is used to reduce cardiac output while the delivery balloon is inflated to deploy the prosthesis within the annulus. Percutaneous aortic prosthetic valve implantation was attempted in 18 patients (aged 81+/-6 years) in whom surgical risk was deemed excessive because of comorbidities. Iliac arterial injury, seen in the first 2 patients, did not recur after improvement in screening and access site management. Implantation was successful in 14 patients. After successful implantation, the aortic valve area increased from 0.6+/-0.2 to 1.6+/-0.4 cm2. There were no intraprocedural deaths. At follow-up of 75+/-55 days, 16 patients (89%) remained alive. CONCLUSIONS: This initial experience suggests that percutaneous transarterial aortic valve implantation is feasible in selected high-risk patients with satisfactory short-term outcomes.

Procedural efficacy and complications of X-Sizer thrombectomy in de novo and stented lesions.

Angiographic thrombus is associated with poorer procedural and clinical outcomes. We report our experience with the X-Sizer thrombectomy device (EndiCOR Medical) from March 2001 to December 2002. Indications for use in 44 patients (33 male; mean age, 60) included myocardial infarction (27), unstable angina (6), periprocedural thrombosis (2), acute (< 24 hr) stent thrombosis (1), and subacute (> 24 hr) stent thrombosis (8). Three cases involved vein grafts. Deployment was successful in 42/44. Difficulty traversing the stent occurred in 5/9 cases of in-stent thrombosis. Median TIMI flow increased from 1 to 2 (P = 0.01) postthrombectomy. Median final TIMI flow was 3. Complications included dissection (1), perforation, device jam on stent (1), disruption of a covered stent (1), distal macro-embolization (4), and transient no-reflow (5). The X-Sizer thrombectomy device improves TIMI flow but does not always prevent distal embolization. Care is needed when treating in-stent thrombosis.

The profile of cardiac patients with renal artery stenosis.

OBJECTIVES: We examined the prevalence and severity of renal artery stenosis (RAS) in patients undergoing cardiac catheterization who were deemed at risk for RAS based on clinical or laboratory criteria for study entry, but who had not previously been suspected of having RAS. BACKGROUND: The diagnosis of atherosclerotic RAS remains problematic because its clinical manifestations are nonspecific. METHODS: Consecutive patients undergoing non-emergent cardiac catheterization at a single institution during a 12-month period were evaluated using standardized clinical, laboratory, and angiographic criteria. Patients exhibiting at least one of four predefined selection criteria (severe hypertension, unexplained renal dysfunction, acute pulmonary edema with hypertension, or severe atherosclerosis) were prospectively registered and underwent coincident diagnostic renal angiography. RESULTS: Renal angiography was performed in 851 patients and was diagnostic in 837. Angiographically evident renal atherosclerosis was present in 39% of the population, with RAS > or =50% in 120 (14.3%) and severe stenosis (> or =70%) in 61 (7.3%). Severe stenosis was present in 48 (7%) patients with severe atherosclerosis, 38 (16%) with renal dysfunction, 25 (9%) with hypertension, and 2 (22%) with acute pulmonary edema with hypertension. The prevalence was higher in those exhibiting multiple selection criteria. In a multivariate model, severe RAS was associated with age, female gender, reduced creatinine clearance, increased systolic blood pressure, and peripheral or carotid artery disease. CONCLUSIONS: In a population at risk of, but not previously suspected of having RAS, severe RAS is associated with simple and readily determined clinical and laboratory patient characteristics. These data facilitate focused application of diagnostic renal angiography.