Thirty-day outcomes from the Society for Vascular Surgery Vascular Quality Initiative thoracic endovascular aortic repair for type B dissection project.

OBJECTIVE: The purpose of the Society for Vascular Surgery Vascular Quality Initiative thoracic endovascular aortic repair (TEVAR) for dissection project is to assess the effectiveness of TEVAR for type B dissection by evaluation in a prospective quality improvement registry. Here we describe the project cohort and 30-day outcomes of TEVAR for both acute dissection (AD) and chronic dissection (CD) patients and focus specifically on outcomes of uncomplicated AD patients based on timing of treatment. METHODS: Summary statistics were performed comparing patients with AD (<30 days) and patients with CD. Both groups were further divided into those with complicated (ie, malperfusion or rupture) or uncomplicated presentation. Further subdivision of the uncomplicated AD patients into treatment at ≤48 hours, >48 hours to <7 days, ≥7 days to ≤14 days, and >14 days to <30 days was performed. Kaplan-Meier analysis was performed for 30-day survival and freedom from reintervention. RESULTS: Data for 397 patients (204 AD patients and 193 CD patients) were collected from 40 institutions. Overall, AD patients were younger than CD patients (58.8 vs 62.2 years; P = .003). Technical success, including coverage of the primary entry tear, was 98.0% for AD patients and 99.0% for CD patients, with a trend toward a higher 30-day mortality in AD patients (AD, 9.3%; CD, 5.2%; P = .126). Any degree of procedure-related spinal cord ischemia occurred in 4.4% of AD patients vs 2.1% of CD patients (P = .261), with a deficit at discharge in 3.4% of AD patients vs 0.5% of CD patients (P = .068). Disabling stroke occurred in 2.5% of AD patients vs 1.6% of CD patients (P = .725); retrograde type A dissection occurred in 1.1% of AD patients vs 2.6% of CD patients (P = .412). There was a trend toward a lower freedom from reintervention in AD patients (90.7% vs 94.8%; P = .13). In uncomplicated AD patients, rapid aortic expansion was more common in the treatment groups of ≥7 days to ≤14 days and >14 days to <30 days compared with those treated within 7 days of dissection (P = .042). The uncomplicated AD cohorts based on timing of treatment were otherwise similar in demographics and presentation, with no significant differences in 30-day mortality or serious complications, such as spinal cord ischemia, stroke, or retrograde type A dissection. The 30-day reintervention rate for uncomplicated AD patients was 5.8%, with no apparent differences in reintervention rates according to timing of treatment of initial TEVAR. CONCLUSIONS: As expected, AD patients demonstrated a trend toward a higher 30-day mortality and lower freedom from reintervention compared with CD patients. Mortality at 30 days after TEVAR for uncomplicated AD was 5.8%, and there were no clear patterns in mortality or reintervention based on timing of treatment. Further study and evaluation at longer follow-up are needed to determine the impact of timing of intervention in uncomplicated AD patients.

Innovative postmarket device evaluation using a quality registry to monitor thoracic endovascular aortic repair in the treatment of aortic dissection.

OBJECTIVE: United States Food and Drug Administration (FDA)-mandated postapproval studies have long been a mainstay of the continued evaluation of high-risk medical devices after initial marketing approval; however, these studies often present challenges related to patient/physician recruitment and retention. Retrospective single-center studies also do not fully represent the spectrum of real-world performance nor are they likely to have a sufficiently large enough sample size to detect important signals. In recent years, The FDA Center for Devices and Radiological Health has been promoting the development and use of patient registries to advance infrastructure and methodologies for medical device investigation. The FDA 2012 document, "Strengthening the National System for Medical Device Post-market Surveillance," highlighted registries as a core foundational infrastructure when linked to other complementary data sources, including embedded unique device identification. The Vascular Quality Initiative (VQI) thoracic endovascular aortic repair for type B aortic dissection project is an innovative method of using quality improvement registries to meet the needs of device evaluation after market approval. Here we report the organization and background of this project and highlight the innovation facilitated by collaboration of physicians, the FDA, and device manufacturers. METHODS: This effort used an existing national network of VQI participants to capture patients undergoing thoracic endovascular aortic repair for acute type B aortic dissection within a registry that aligns with standard practice and existing quality efforts. The VQI captures detailed patient, device, and procedural data for consecutive eligible cases under the auspices of a Patient Safety Organization (PSO). Patients were divided into a 5-year follow-up group (200 acute; 200 chronic dissections) and a 1-year follow-up group (100 acute; 100 chronic). The 5-year cohort required additional imaging details, and the 1-year group required standard VQI registry data entry. RESULTS: The sample size of patients in each of the 5-year acute and chronic dissection arms was achieved ≤24 months of project initiation, and data capture for the 1-year follow-up group is also nearly complete. Data completeness and follow-up has been excellent, and the two FDA-approved devices for dissection are equally represented. CONCLUSIONS: Although the completeness of long-term follow-up is yet to be determined, the rapidity of data collection supports the use of this construct for device assessment after market approval. The alignment of this effort with routine clinical practice and ongoing quality improvement initiatives is critical and has required minimal additional effort by practitioners, thus facilitating patient inclusion. Importantly, the success and development of this unique project has helped inform FDA strategy for future device evaluation after market approval.

Application of Investigational Device Exemptions regulations to endograft modification.

For patients with complex aortic aneurysms that cannot be treated effectively with currently approved endografts, physicians have made fenestrations in marketed devices and constructed branched grafts by creatively implanting available endograft components. For the most part, these procedures are being done outside of clinical studies by individual physicians. Although these novel approaches may be useful in the treatment of individual patients, the current ad hoc use of physician-created fenestrated and branched devices may not result in the unbiased capture and reporting of data regarding short- and longer-term outcomes. As a result, unsubstantiated conclusions regarding the safety and effectiveness of these procedures may be drawn. Well-designed and executed clinical studies are necessary to adequately assess the benefits and risks of these techniques. Because these interventions involve the use of significant risk devices, these studies need to be conducted under United States Food and Drug Administration-approved Investigational Device Exemptions (IDE) applications. Although this regulatory process adds complexity to the application of these creative techniques, the IDE regulations assure that patient protection measures are followed and data are captured to assess safety and effectiveness. This approach creates opportunities to advance the development of innovative, beneficial devices and procedures to treat complex aortic aneurysms.

The influence of gender and aortic aneurysm size on eligibility for endovascular abdominal aortic aneurysm repair.

OBJECTIVES: The purpose of this study was to compare the eligibility of men and women with infrarenal abdominal aortic aneurysms (AAAs) for on-label endovascular aneurysm repair (EVAR) as part of the clinician-Food & Drug Administration (FDA) collaborative effort, the Characterization of Human Aortic Anatomy Project (CHAP). METHODS: Computed tomography (CT) scans with 3D reconstruction from a single institution obtained between July 1996 and December 2009, including standardized measurements by a blinded third-party (M2S, West Lebanon, NH) were examined. For inclusion, abdominal aortic aneurysm (AAA) had to be infrarenal, unrepaired, and >5 cm, or 4 cm to 5 cm if the orthogonal sac diameter was more than twice the aortic diameter at the renal level. Scans were included regardless of subsequent EVAR, open repair, or lack of treatment. One thousand sixty-three unique, unrepaired AAAs were analyzed. RESULTS: Neck length, diameter, and angulation differ for women (P < .001) even after adjustment for patient age and AAA size. EVAR eligibility based on device Instructions for Use (IFU) criterion is affected by gender. Neck length <15 mm was found in 47% of men and 63% of women. Neck angulation exceeding 60 degrees was found in 12% of men and 26% of women. Minimum iliac diameter of 6 mm was found in 35% of men and 55% of women. Only 32% of men and 12% of women met all three neck criterion and had iliac lumen diameters >6 mm. Logistic regression modeling shows that older patient age (odds ratio [OR], 0.84 per decade), increased aneurysm diameter (OR, 0.70 per cm), and female gender (OR, 0.4) are each independently associated with decreased odds of meeting all device IFU neck criterion (P < .05). EVAR eligibility by neck criterion does not decline significantly until AAA size exceeds 5.5 cm in women and 6.5 cm in men. CONCLUSION: Women are significantly less likely to meet device IFU criterion for EVAR. Aortic neck criteria and iliac access are important for men and women, but more women than men fail to meet IFU criterion. Devices that accommodate shorter infrarenal AAA neck length will have the greatest impact on expanding on-label EVAR regardless of gender. Lower profile devices and those that accommodate higher neck angulation are expected to expand EVAR eligibility further for women. EVAR eligibility is unlikely to be lost as AAAs enlarge to 5.5 cm in women and 6.5 cm in men. Observation of small AAAs until they reach the standard threshold size for repair should not compromise EVAR eligibility.

Overcoming the Challenges of Conducting Early Feasibility Studies of Medical Devices in the United States.

Initial clinical studies of new medical technologies involve a complex balance of research participant benefits versus risks and costs of uncertainty when novel concepts are tested. The Food and Drug Administration Center for Devices and Radiological Health has recently introduced the Early Feasibility Study (EFS) Program for facilitating the conduct of these studies under the Investigational Device Exemption regulations. However, a systematic approach is needed to successfully implement this program while affording appropriate preservation of the rights and interests of patients. For this to succeed, a holistic reform of the clinical studies ecosystem for performing early-stage clinical research in the United States is necessary. The authors review the current landscape of the U.S. EFS and make recommendations for developing an efficient EFS process to meet the goal of improving access to early-stage, potentially beneficial medical devices in the United States.

Evolution and future of preclinical testing for endovascular grafts.

The preclinical testing of endovascular grafts has evolved significantly since the creation and early testing of these devices; however, there are continued limitations in using preclinical testing to predict clinical performance. Early testing was conducted in the absence of standards and guidance specific to endovascular grafts, and references available for vascular grafts and stents did not adequately account for the complexity of endovascular graft systems. Failure of early-generation devices suggested that the testing being conducted was inadequate and that there was a lack of understanding of the in vivo environment. These concerns led to several efforts to improve preclinical testing. The Food and Drug Administration (FDA) sponsored a workshop to discuss the limitations inherent in testing of endovascular grafts, and an ISO standard for endovascular grafts was developed. Publication of the standard in 2003 succeeded in standardizing testing and reporting across device manufacturers; however, several clinical failure modes, such as migration and stent fractures, continued to be unpredicted by current preclinical testing. This, coupled with knowledge gained from additional clinical experience, led the FDA to hold a second workshop to discuss the benefits and limitations of current testing and propose future testing that may better predict device performance. This workshop was successful in accurately describing past testing, determining what has been learned, identifying issues that have not been adequately addressed, proposing modifications to address these limitations, and discussing how the proposed modifications should be implemented. While significant progress has been made in endovascular graft testing, continued collaboration among industry, academia, regulators, and clinicians will provide continued improvement in the predictability of device performance.

Preclinical testing for aortic endovascular grafts: results of a Food and Drug Administration workshop.

BACKGROUND: Since their introduction into clinical trials in the United States, endovascular aortic grafts have shown various types of problems. Although details of design and construction vary between different endovascular grafts and failure modes have had a variety of causes and clinical effects, the inability of preclinical testing to predict these failures remains common to all endovascular grafts. The need to improve preclinical testing in an attempt to reduce clinical device failures resulted in a Food and Drug Administration-sponsored workshop on endovascular graft preclinical testing held in Rockville, Md, from July 31 to August 1, 2001. FORMAT: The workshop was not designed as a consensus conference. Instead, it provided a forum for bringing stakeholders together to define problems and identify areas of agreement and disagreement. The workshop had 34 invited participants who represented device manufacturers, the medical community, the Food and Drug Administration, and testing facilities, and international attendance was more than 120 people. OUTCOME: Discussion centered on: 1, defining the physiologic, anatomic, and morphologic characteristics of abdominal aortic aneurysms before and after endovascular graft treatment; 2, identifying the types of failures that have been observed clinically; and 3, determining which characteristics should be considered during preclinical modeling to better predict clinical performance. Attendees agreed to the need to better define and address anatomic characteristics and changes in the aneurysm after endograft treatment to optimize preclinical testing. Much discussion and little agreement occurred on the importance of flow-related forces on graft performance or the need or ability to define and model physiologic compliance during durability testing. The discussion and conclusions are summarized in this paper and are provided in detail at: http://www.fda.gov/cdrh/meetings/073101workshop.html. CONCLUSION: The workshop raised awareness of significant performance issues and the challenges of modeling the extremely variable and relatively undefined environment of abdominal aortic aneurysms. Through the interactive format of the workshop, participants identified areas of preclinical testing, device design, and aspects of the simulated environment that need further consideration.