Patrick J. Geraghty

Suggested objective performance goals and clinical trial design for evaluating catheter-based treatment of critical limb ischemia

OBJECTIVE To develop a set of suggested objective performance goals (OPG) for evaluating new catheter-based treatments in critical limb ischemia (CLI), based on evidence from historical controls. METHODS Randomized, controlled trials of surgical, endovascular, and pharmacologic/biologic treatments for CLI were reviewed according to specified criteria regarding study population and data quality. Line-item data were obtained for selected studies from the sponsor/funding agency. A set of specific outcome measures was defined in accordance with the treatment goals for the CLI population. Risk factors were examined for their influence on key endpoints, and models of stratification based on specific clinical and anatomic variables developed. Sample size estimates were made for single-arm trial designs based on comparison to the suggested OPG. RESULTS Bypass with autogenous vein was considered the established standard, and data compiled from three individual randomized, controlled trials (N = 838) was analyzed. The primary efficacy endpoint was defined as perioperative (30-day) death or any major adverse limb event (amputation or major reintervention) occurring within one year. Results of open surgery controls demonstrated freedom from the primary endpoint in 76.9% (95% confidence interval [CI] 74.0%-79.9%) of patients at one year, with amputation-free survival (AFS) of 76.5% (95% CI 73.7%-79.5). An additional 3% non-inferiority margin was suggested in generating OPG for catheter-based therapies. Defined clinical (age > 80 years and tissue loss) and anatomic (infra-popliteal anatomy or lack of good quality saphenous vein) risk subgroups provided significantly different point estimates and OPG threshold values. CONCLUSIONS For new catheter-based therapies in CLI, OPGs offer a feasible approach for pre-market evaluation using non-randomized trial designs. Such studies should incorporate risk stratification in design and reporting as the CLI population is heterogeneous with respect to baseline variables and expected outcomes. Guidelines for CLI trial design to address consistency in study cohorts, methods of assessment, and endpoint definitions are provided.

Society for Vascular Surgery practice guidelines for atherosclerotic occlusive disease of the lower extremities: Management of asymptomatic disease and claudication

Peripheral arterial disease (PAD) continues to grow in global prevalence and consumes an increasing amount of resources in the United States health care system. Overall rates of intervention for PAD have been rising steadily in recent years. Changing demographics, evolution of technologies, and an expanding database of outcomes studies are primary forces influencing clinical decision making in PAD. The management of PAD is multidisciplinary, involving primary care physicians and vascular specialists with varying expertise in diagnostic and treatment modalities. PAD represents a broad spectrum of disease from asymptomatic through severe limb ischemia. The Society for Vascular Surgery Lower Extremity Practice Guidelines committee reviewed the evidence supporting clinical care in the treatment of asymptomatic PAD and intermittent claudication (IC). The committee made specific practice recommendations using the GRADE (Grades of Recommendation Assessment, Development and Evaluation) system. There are limited Level I data available for many of the critical questions in the field, demonstrating the urgent need for comparative effectiveness research in PAD. Emphasis is placed on risk factor modification, medical therapies, and broader use of exercise programs to improve cardiovascular health and functional performance. Screening for PAD appears of unproven benefit at present. Revascularization for IC is an appropriate therapy for selected patients with disabling symptoms, after a careful risk-benefit analysis. Treatment should be individualized based on comorbid conditions, degree of functional impairment, and anatomic factors. Invasive treatments for IC should provide predictable functional improvements with reasonable durability. A minimum threshold of a >50% likelihood of sustained efficacy for at least 2 years is suggested as a benchmark. Anatomic patency (freedom from restenosis) is considered a prerequisite for sustained efficacy of revascularization in IC. Endovascular approaches are favored for most candidates with aortoiliac disease and for selected patients with femoropopliteal disease in whom anatomic durability is expected to meet this minimum threshold. Conversely, caution is warranted in the use of interventions for IC in anatomic settings where durability is limited (extensive calcification, small-caliber arteries, diffuse infrainguinal disease, poor runoff). Surgical bypass may be a preferred strategy in good-risk patients with these disease patterns or in those with prior endovascular failures. Common femoral artery disease should be treated surgically, and saphenous vein is the preferred conduit for infrainguinal bypass grafting. Patients who undergo invasive treatments for IC should be monitored regularly in a surveillance program to record subjective improvements, assess risk factors, optimize compliance with cardioprotective medications, and monitor hemodynamic and patency status.

Three-year results of the VIBRANT trial of VIABAHN endoprosthesis versus bare nitinol stent implantation for complex superficial femoral artery occlusive disease

OBJECTIVE The predominant mode of bare nitinol stent failure is diffuse in-stent restenosis, and failure rates correlate to the length and complexity of the treated lesion. Addition of an expanded polytetrafluoroethylene lining to a nitinol stent frame, as found in the VIABAHN endoprosthesis, mitigates the ingrowth of intimal hyperplasia. We compared the long-term outcomes of complex superficial femoral artery disease intervention using the VIABAHN endoprosthesis to those obtained with bare nitinol stent implantation. METHODS One hundred forty-eight patients with symptomatic complex superficial femoral artery disease (TransAtlantic Inter-Society Consensus I class C and D lesions, accompanied by intermittent claudication or ischemic rest pain) were randomized to endovascular intervention using either bare nitinol stent implantation (76 patients) or nonheparin-bonded VIABAHN endoprosthesis deployment (72 patients). Patency, limb hemodynamics, and quality of life were evaluated at 1, 6, 12, 24, and 36 months following intervention. RESULTS The average treated lesion measured 18 ± 8 cm in length, and 58.8% of lesions displayed segmental or complete occlusion. At 3 years, primary patency rates (defined by peak systolic velocity ratio ≤ 2.0 and no target lesion revascularization) did not significantly differ between patients treated with the VIABAHN stent graft and those who received a bare nitinol stent (24.2% vs 25.9%; P = .392). Stent fractures were significantly more common in bare nitinol stents (50.0%) than in the VIABAHN endoprostheses (2.6%). Primary-assisted patency rates were higher in those receiving bare nitinol stents than the VIABAHN stent graft (88.8% vs 69.8%; P = .04), although secondary patency rates did not differ between bare nitinol stent and stent graft recipients (89.3% vs 79.5%; P = .304). There were no instances of procedure-related mortality or amputation. The hemodynamic improvement and quality measures improved equally in both groups. CONCLUSIONS The long-term outcomes of complex superficial femoral artery disease intervention using the VIABAHN endograft and bare nitinol stents are similar. Although primary patency rates are low in both study arms, excellent primary-assisted and secondary patency rates were achieved, with sustained augmentation of limb perfusion and quality-of-life measures. Patency rates diminish most rapidly in the first year after device implantation.

Endoluminal graft repair for abdominal aortic aneurysms in high-risk patients and octogenarians: is it better than open repair?

ObjectiveTo analyze the short-term and midterm results of open and endoluminal repair of abdominal aortic aneurysms (AAA) in a large single-center series and specifically in octogenarians. MethodsBetween January 1997 and October 2000, 470 consecutive patients underwent elective repair of AAA. Conventional open repair (COR) was performed in 210 patients and endoluminal graft (ELG) repair in 260 patients. Ninety of the patients were 80 years of age or older; of these, 38 underwent COR and 52 ELG repair. ResultsPatient characteristics and risk factors were similar for both the entire series and the subgroup of patients 80 years or older. The overall complication rate was reduced by 70% or more in the ELG versus the COR groups. The postoperative death rate was similar for the COR and ELG groups in the entire series and lower (but not significantly) in the ELG 80 years or older subgroup versus the COR group. The 36-month rates of freedom from endoleaks, surgical conversion, and secondary intervention were 81%, 98.2%, and 88%, respectively. ConclusionThe short-term and midterm results of AAA repair by COR or ELG are similar. The death rate associated with this new technique is low and comparable, whereas the complication rate associated with COR in all patients and those 80 years or older in particular is greater and more serious than ELG repair. Long-term results will establish the role of ELG repair of AAA, especially in elderly and high-risk patients.

Outcomes of percutaneous endovascular intervention for type II endoleak with aneurysm expansion.

OBJECTIVE Type II endoleak (T2EL) with aneurysm expansion is believed to place patients at risk for aneurysm-related mortality (ARM). Treatment with glue and/or coil embolization of the aneurysm sac, inferior mesenteric artery (IMA), and lumbar branches via translumbar or transarterial approaches has been utilized to ablate such endoleaks, and thus decrease ARM. We evaluated the midterm results of percutaneous endovascular treatment of T2EL with aneurysm expansion. METHODS Single-institution, 5-year (January 2003 to August 2008) retrospective study of all endovascular interventions for T2EL with sac expansion. Blinded, independent review of all available pre- and post-T2EL intervention computed tomography (CT) scans was performed. Aneurysm sac maximal transverse diameters and aneurysm sac growth rates prior to and following T2EL intervention were analyzed. RESULTS Forty-two patients (34 male, eight female; mean age, 75) underwent T2EL intervention at 26 ± 20 months after endovascular aneurysm repair (EVAR) and were subsequently followed for 23 ± 20 months. Seven out of 42 patients (17%) underwent repeat T2EL intervention. Interventions included 44 translumbar sac embolizations, and transcatheter embolizations of nine IMAs and seven lumbar/hypogastric arteries. Aneurysm diameter was 6.1 ± 1.6 cm at EVAR, 6.6 ± 1.5 cm at initial T2EL treatment, and 6.9 ± 1.7 cm at last follow-up. There were no significant differences in the rates of aneurysm sac growth pre- and post-T2EL treatment. At last follow-up imaging, recurrent or persistent T2EL was noted in 72% of patients. Of 42 patients, nine (21%) received operative endoluminal correction of occult type I or type III endoleaks that were diagnosed during the T2EL angiographic intervention. There were no aneurysm ruptures or ARMs during follow-up; overall mortality for the 5-year study period was 24%. CONCLUSIONS In this series, percutaneous endovascular intervention for type II endoleak with aneurysm sac growth does not appear to alter the rate of aneurysm sac growth, and the majority of patients display persistent/recurrent endoleak. However, diagnostic angiographic evaluation may reveal unexpected type I and III endoleaks and is therefore recommended for all patients with T2EL and sac growth. While coil and glue embolization of aneurysm sac and selected branch vessels does not appear to yield benefit in our series, the diagnosis and subsequent definitive treatment of previously occult type I and III endoleaks may explain the absence of delayed rupture and ARM in our series.

Long-term outcome of endovascular popliteal artery aneurysm repair.

BACKGROUND Popliteal artery aneurysms have traditionally been repaired with an open surgical approach. However, endovascular popliteal artery repair (EVPAR) has been used in selected patients because of its less invasive nature. In this report, we present our long-term outcomes for EVPAR. METHODS Retrospective review of all patients who underwent EVPAR at a single academic institution between September 2002 and March 2006. These patients were evaluated for patency, need for secondary intervention, amputation-free survival, and overall survival. RESULTS A total of 15 limbs in 13 patients were treated with EVPAR during the study period. All EVPAR were performed using the Viabahn(®) endoprostheses, with an average of 1.67 stents per limb. The mean age of the patients was 74.6 years (range, 66-84). Technical success was achieved in 100% and all limbs had initial postoperative ankle-arm indices of ≥ 1.0. Mean duration of follow-up was 54 months (range, 42-70). Two patients died of unrelated causes at 3 and 38 months with intact limbs, and one patient was lost to follow-up. Two limbs developed type I or III endoleaks, and were successfully treated with additional endovascular stent placement, resulting in a primary patency rate of 84.6% and secondary patency rate of 100%. There were no instances of limb loss during the follow-up period, yielding both amputation-free survival and overall survival rates of 85.7%. CONCLUSIONS Long-term follow-up of this cohort of EVPAR patients suggests that in selected patients, this is a durable technique, capable of achieving excellent patency rates and limb preservation. Further large-scale clinical trials are warranted to help define optimal candidates for this technique.

A 5-Year Comparison of EVAR for Large and Small Aortic Necks

Purpose: To compare the long-term outcomes of endovascular aneurysm repair (EVAR) using the Talent endograft for abdominal aortic aneurysms (AAAs) with large and small aortic necks. Methods: Data on 156 patients (142 men; mean age 74.1 years, range 41–89) with adequate preoperative imaging were obtained from the prospective, nonrandomized, multicenter Talent eLPS trial, which enrolled patients from February 2002 to April 2003. Subgroup analyses were performed for AAAs with a large aortic neck diameter (≥28 mm; n=53, group 1) and those with smaller necks (<28 mm; n = 103, group 2). Safety and effectiveness endpoints were evaluated at 30 days, 1 year, and 5 years post procedure. Results: Patients in both groups had similar gender and risk factor profiles. However, group 1 was significantly older (mean age 76.5 versus 72.9 years; p<0.01). Aside from neck diameter, the 2 groups had similar mean neck length and angulation. Group 1 also had a larger maximum aneurysm diameter (mean 58.2 versus 53.4 mm; p<0.01). At 1 year, the 2 groups had similar effectiveness endpoint results. There was a significantly lower freedom from major adverse events (MAEs) for group 1 at 30 days (79.2% versus 95.1%; p<0.01). While this trend continued to 1 year, the difference lost statistical significance (72.0% versus 85.1%; p=0.08). Freedom from all-cause mortality at 30 days (94.4% versus 100%; p<0.04) and aneurysm-related death at 1 year (93.3 versus 100%; p<0.04) also was significantly lower for group 1. At 5 years, there were no significant differences in the rates of endoleaks or aneurysm changes. The 5-year rates for freedom from aneurysm-related mortality for groups 1 and 2 were 91.2% and 98.7% (p=NS), respectively. There were 5 instances of migration in this study, all occurring in group 1 patients. Conclusion: AAAs with aortic necks ≥28 mm can be treated with endovascular devices with acceptable results at 5 years. However, these patients have a higher rate of MAEs within the first year and higher migration rates at 5 years. In addition, they have a lower freedom from all-cause mortality at 30 days and aneurysm-related death at 1 year. Careful patient selection, accurate device deployment, and continued follow-up are necessary to optimize long-term results in this patient population.

Delayed Complications after Endovascular AAA Repair in Women

PURPOSE To assess whether women suffer more delayed complications or require more interventions after endovascular abdominal aortic aneurysm (AAA) repair. METHODS Over a 2-year period, 245 patients (203 men, 42 women) underwent endovascular repair with the AneuRx stent-graft at our institution. Baseline, operative, and follow-up data were reviewed and outcomes compared between men and women for complications or secondary procedures beyond the 30-day postoperative period. RESULTS The 42 (17.1%) women treated with the AneuRx graft experienced more technical complications (17% versus 8.3%; p<0.05) and acute conversions to open repair (6/7, 86%; p=0.0005). At 30 days, systemic morbidity was significantly higher in women (26% versus 5.3%; p=0.001.) However, mortality (2.3% versus 1.5%), length of hospital stay (2.6 versus 2.9 days), and major endoleaks at discharge (0% versus 1.6%) were similar. Over a mean follow-up of 11.3 months (range 1-26), graft limb occlusion occurred more frequently in female patients (12.2% versus 2.5%; p=0.05), and secondary procedures were required in a significantly higher number of women (29% versus 9%; p<0.05). Three patients in each group (25% of women versus 17% of men) who had secondary procedures required additional interventions. Although not statistically significant, the mortality in women during follow-up was higher (9.7% versus 5%); 2 deaths were directly related to graft complications in the female group. CONCLUSIONS Endoluminal AAA repair in women presents a technical challenge at the time of operation and may cause more frequent late complications, necessitating close postprocedural surveillance and prompt correction of complications to avoid potentially catastrophic outcomes. Reassessment of inclusion criteria for women may be necessary.

A comparative analysis of the outcomes of aortic cuffs and converters for endovascular graft migration

OBJECTIVE Proximal attachment failure, often leading to graft migration, is a severe complication of endovascular aneurysm repair (EVAR). Aortic cuffs have been used to treat proximal attachment failure with mixed results. The Zenith Renu AAA Ancillary Graft (Cook Inc, Bloomington, Ind) is available in two configurations: converter and main body extension. Both provide proximal extension with active fixation for the treatment of pre-existing endovascular grafts with failed or failing proximal fixation or seal in patients who are not surgical candidates. We prospectively compared the outcomes of patient treatment with these two device configurations. METHODS From September 2005 to May 2008, a prospective, nonrandomized, postmarket registry was conducted to collect data from 151 patients treated at 95 institutions for proximal aortic endovascular graft failure using the Renu graft. Treatment indications included inadequate proximal fixation or seal, for example, migration, and type I and III endoleak. A total of 136 patients (90%) had migration, 111 (74%) had endoleak, and 94 (62%) had endoleaks and graft migration. AneuRx grafts were present in 126 patients (83%), of which 89 (59%) were treated with a converter and 62 (41%) with a main body extension. Outcomes using converters vs main body extensions for endoleak rates, changes in aneurysm size, and ruptures were compared. RESULTS Preprocedural demographics between the two groups did not differ significantly. Procedural success rates were 98% for the converter group and 100% for the main body extension group. At a mean follow-up of 12.8 +/- 7.5 months, no type III endoleaks (0%)were identified in the converter group, and five (8%) were identified in the main body extension group. There were no aneurysm ruptures in patients treated with converters (0%) and three ruptures (5%) in patients treated with main body extensions. Each patient with aneurysm rupture had been treated with a Renu main body extension, developed a type III endoleak, and underwent surgical conversion. Two of the three patients died postoperatively. CONCLUSIONS Proximal attachment failure and graft migration are potentially lethal complications of EVAR. Proximal graft extension using an aortic cuff is the easiest technique for salvaging an endovascular graft. Unfortunately, it has a predictable failure mode (development of a type III endoleak due to component separation) and is associated with a significantly higher failure rate than with the use of a converter. EVAR salvage with a converter and a femorofemoral bypass is a more complex but superior option for endovascular graft salvage.

Covered stenting of the superficial femoral artery using the Viabahn stent-graft.

High initial technical success rates for superficial femoral artery revascularization are possible using multiple modalities. For these interventions to pose a serious challenge to open surgical bypass, improved primary patency in mid- and long-term follow-up must be achieved. In several smaller studies, covered stenting of the superficial femoral artery has shown superior patency at 2 years after intervention. The ongoing VIBRANT trial randomizes patients to superficial femoral artery intervention with either bare nitinol stents or Viabahn covered stents. The 3-year outcomes data from this trial will better define the role of percutaneous intervention for complex superficial femoral artery disease.