Short-Term Outcomes After Retrograde Versus Antegrade Crossing Approaches for Femoropopliteal Occlusive Disease

Abstract

Objective. To compare short- and mid-term outcomes of patients with femoropopliteal (FP) occlusive disease treated with a retrograde vs antegrade crossing strategy. Background. Few studies have directly compared procedural details and outcomes after retrograde vs antegrade crossing of FP lesions. Methods. Patients undergoing retrograde approaches to FP lesions were identified from the multicenter Excellence in Peripheral Artery Disease (XLPAD) registry between 2007 and 2015. These -patients were matched 1:1 to patients treated with antegrade crossing strategies based on age, gender, comorbidities, indication for procedure, and lesion characteristics. Technical success, major adverse limb events (MALEs), and overall device cost were compared between retrograde and antegrade-only crossing. Results. A total of 116 patients (58 antegrade and 58 retrograde) were included. The retrograde group had higher prevalence of coronary artery disease and presence of chronic total occlusions. The retrograde approach was associated with significantly longer procedural time (186 ± 70 minutes vs 124.4 ± 60 minutes; P<.001), but similar technical success (91.4% vs 96.6%; P=.24). There was no significant difference in perioperative morbidity. Patients treated with a retrograde approach had a lower total amputation rate (8.6% vs 22.4%; P=.04) and no difference in overall mortality (8.6% vs 5.2%; P=.47). Mean procedural costs were similar in the antegrade and retrograde groups. Conclusion. In patients with similar disease characteristics, a retrograde approach to FP occlusive disease was associated with longer procedural time, but improved limb salvage, without significant difference in procedural cost.

Keywords: chronic total occlusion, peripheral artery disease, superficial femoral artery, tibiopedal access

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Significant improvements in technology, techniques, and device design have expanded the role of endovascular therapy for patients with peripheral arterial disease (PAD). However, the conventional antegrade crossing approach fails in nearly 10%-20% of patients with complex lesions, including femoropopliteal (FP) occlusions.^1,2 This highlights the multiple challenges interventionists face in the presence of multilevel PAD and long-segment arterial occlusions. In cases of critical limb ischemia (CLI), failure of antegrade recanalization is often associated with increased risk of major amputation and death.³

Retrograde approaches to crossing FP lesions have become more common in practice, especially when antegrade crossing fails. One of the earliest series of tibiopedal arterial access to treat infrainguinal disease, the tibiopedal arterial minimally invasive (TAMI) technique, demonstrated a high rate of successful revascularization with few complications.⁴ The initial description of the TAMI technique involved tibiopedal access and subsequent treatment of mainly tibial occlusive disease through the retrograde approach.⁴ In the subsequent years, the retrograde approach has been used as the sole source of access with the TAMI technique, as well as in dual-access techniques involving both antegrade and retrograde accesses, such as the subintimal arterial flossing with antegrade-retrograde intervention (SAFARI) technique.⁵ Although several series have confirmed excellent technical success rates and a low incidence of local complications, few studies directly compare procedural details and mid-term outcomes of retrograde vs antegrade approaches to treat specifically FP occlusive disease in PAD patients with similar disease characteristics.^1,6,7 The goal of this study is to compare the short- and mid-term outcomes of matched patients with FP occlusive disease treated with a retrograde vs an antegrade crossing approach.

Methods

Subjects. This study is a retrospective, multi-institutional analysis from the ongoing Excellence in Peripheral Arterial Disease (XLPAD) registry (NCT01904851). XLPAD is a multicenter registry that evaluates the outcomes of patients undergoing endovascular interventions. Details of the XLPAD registry have been published previously. The large number of patients in this dataset provided an opportunity to compare matched patients who underwent a peripheral intervention for FP disease with antegrade and/or retrograde crossing strategies. The study protocol was approved by the institutional review boards of the participating centers. All patients provided consent to the planned operative procedure. Patients from only 3 of the participating sites (Dallas Veterans Affairs Medical Center, Denver Veteran Affairs Medical Center, and the University of Texas Southwestern Medical Center) were included in this analysis, which facilitated independent review of medical records, procedural documentation, and angiograms when available.

All patients from the 3 institutions that were included in the XLPAD registry and underwent retrograde crossing of FP lesions between 2007 and 2015 were included in the study.  These patients were matched 1:1 to patients in the XLPAD registry who underwent antegrade crossing of FP lesions based on age, gender, comorbidities, indication for procedure, and lesion characteristics. Comorbidities included hypertension, diabetes mellitus, hyperlipidemia, and chronic kidney disease. Indication for the procedure was defined by the Rutherford grade and ankle-brachial index (ABI). Access selection was made by the treating physician. Lesion characteristics were matched between the antegrade and retrograde crossing groups in the following prioritization: the number of below-the-knee runoff vessels patent at the time of procedure, lesion length, presence of in-stent restenosis, presence of heavy calcification, and presence of chronic total occlusion (CTO) of the lesion being treated. Heavy calcification was defined as >5 mm of calcification seen on either side of the target vessel demonstrated during the procedure. Proximal cap morphology on angiography was classified as either blunt or tapered. Revascularization strategy was determined by the treating physician and included one or a combination of atherectomy, percutaneous transluminal angioplasty (PTA), bare-metal stent (BMS) placement, drug-coated balloon (DCB) angioplasty, or drug-eluting stent (DES) placement.

Outcomes and definitions. The outcomes examined were technical success, procedural success, procedural complications, 30-day and 12-month cardiovascular and limb adverse events, and procedural duration and cost. Postprocedural angiography was used to determine technical success, which was defined <30% residual stenosis, and procedural success, which was defined as technical success in the absence of postprocedure complications. Local procedural complications were defined as flow-limiting dissection, perforation that required an intervention, or access-site hematoma. Development of renal failure, distal embolization, or need for emergent surgery as result of failed intervention were measured as well. Cardiovascular and limb outcomes at 30 days and 12 months included all-cause death, non-fatal myocardial infarction (MI), ischemic stroke, stent thrombosis, repeat target-limb revascularization, and amputation (major and minor). Major amputations were defined as transtibial amputations or higher while minor amputations were those that were inframalleolar. Procedural characteristics such as procedural time, fluoroscopy time, and procedural cost were analyzed. Procedural cost was an estimate of device cost in United States dollars based on the documented wires, catheters, balloons, and/or stents that were used per procedure.

Statistical analysis. Descriptive statistics—frequencies and percentages for categorical variables and mean ± standard deviation for continuous variables—are presented for all samples and grouped by antegrade and retrograde crossing approaches. Cochran-Mantel-Haenszel and 2-sided Wilcoxon rank-sum statistics were used to test a group difference in categorical and continuous variables, respectively, between antegrade and retrograde crossing groups.

Results

A total of 116 patients from 3 institutions were included, with 58 patients each in the retrograde and antegrade groups. The baseline characteristics are listed in Table 1. Overall, all baseline characteristics were well matched; mean age was 66 years and 91.4% of the patients were men. Approximately 55% of patients had diabetes mellitus and 19% had chronic kidney disease.  Hypertension and hyperlipidemia were highly prevalent (>80%) in this cohort. The retrograde group had a higher incidence of coronary artery disease (67%). The majority of patients studied had Rutherford category 3 or higher, with 55.2% having Rutherford category 4 or higher. The antegrade group had more patients with Rutherford category 3 disease than the retrograde group. Mean ABI was 0.70 in both groups. Forty-six patients (79%) in the retrograde group had an unsuccessful antegrade crossing attempt, which took place in a separate procedure in 4 cases (8.7%).

The lesion characteristics of the cases studied are demonstrated in Table 2. The 2 groups had similar below-the-knee runoff vessels, average treated lesion length, prevalence of in-stent restenosis, and heavy calcification. However, degree of stenosis was significantly different between the 2 groups, with the retrograde group comprising CTOs exclusively (100% vs 74.1%; P<.001). The CTO distribution, isolated FP vs FP and tibioperoneal, did not differ significantly between the antegrade and retrograde groups. Proximal cap morphology data were available for 67% of the cohort. There was no significant difference in proximal cap morphology between the 2 groups (antegrade: 16 tapered, 19 blunt; retrograde: 18 tapered, 25 blunt; P=.73).

Procedural characteristics were compared between the 2 groups (Table 2). The retrograde approach was associated with significantly longer procedural time (186.1 minutes vs 124.4 minutes; P<.001) and fluoroscopy time (53.9 minutes vs 32.1 minutes; P<.001) than the antegrade group. However, many of the cases with retrograde crossing also involved antegrade crossing attempts. The retrograde and antegrade groups had similar mean procedural device cost ($4578 vs $5548, respectively; P=.12).

Thirty-day and 12-month outcomes by access group are shown in Table 3. There was no significant difference in procedural or technical success between groups. Procedural complications were overall low. One patient with an intraoperative vessel perforation was managed conservatively and did not require any additional interventions. A flow-limiting dissection in 1 patient was managed with prolonged balloon inflation. Two access-site hematomas were managed conservatively without further intervention.

There was no statistical difference in 30-day cardiovascular or limb outcomes between the 2 groups (Table 3). There was 1 MI, 1 stent thrombosis, and 1 repeat target-limb intervention in the retrograde group. There were 2 and 4 target-limb amputations in the retrograde and antegrade groups, respectively. There was no significant difference between groups in all-cause death, stroke, stent thrombosis, or repeat target-limb revascularization. At 12 months, the retrograde group had a significantly higher rate of MI and the antegrade group had a higher rate of total (major and minor) limb amputations (Table 3). In the antegrade group, 2 patients with minor amputation underwent subsequent major amputation.

Discussion

Although recent studies have demonstrated the safety and efficacy of retrograde crossing of lower-extremity CTO, our current study shows that in patients with FP occlusions, a retrograde crossing technique was associated with improved short-term limb salvage when compared with matched patients treated using an antegrade-only crossing technique.

Endovascular approaches have become increasingly prevalent in the management of lower-extremity PAD, including limb salvage in patients with chronic limb threatening ischemia (CLTI).  Unless there is an adequate segment of greater saphenous vein, the long-term limb salvage results between surgical bypass and endovascular techniques appear similar.² Furthermore, meta-analyses have suggested that initial endovascular, as opposed to surgical, revascularization strategies in patients with CLTI do not impact limb salvage rates up to 3 years.^8,9 Previous literature has suggested that percutaneous tibiopedal access is an effective strategy for the treatment of complex infrainguinal PAD with a low incidence of local access-site complications.^1,6,7 Walker et al prospectively enrolled 197 patients in an international single-arm observational study to assess safety and feasibility of tibiopedal access and retrograde crossing of CTO.¹⁰ The tibial or pedal artery was successfully accessed in 93.4% of patients, and among the patients who had successful access, the CTO was crossed in 85.3%. There were no reported cases of access-site complications in this study. Schmidt et al, however, reported a 3.3% rate of tibial vessel access-site complications (occlusions, dissection, stenosis, thrombosis, arteriovenous fistula) in their cohort of 524 patients with lower-extremity PAD treated with retrograde crossing approaches from tibioperoneal access.⁷

Similar to the current study, a retrospective analysis of data from the PRIME registry compared femoral vs tibiopedal vs dual (femoral and tibiopedal) access for treatment of infrainguinal disease.⁶ This study highlighted the benefit of tibiopedal access in the treatment of infrapopliteal disease; however, the majority of FP disease was treated through sole femoral access. Therefore, the comparison of antegrade vs retrograde crossing approaches in the PRIME Registry was confounded by differences in anatomic disease distribution.

Although our results show significantly longer procedural and fluoroscopy times for retrograde vs antegrade access, the recently published TRIACCESS study demonstrated a significant reduction in case radiation dose when using primary pedal vs primary femoral access (63.2 Dyn vs 153.1 Dyn; P<.01) for the treatment of SFA occlusive disease.¹¹ This randomized, prospective study enrolled 180 patients and reported a 100% technical success rate for both femoral and pedal access, with >95% overall limb-salvage rate at 6 months for their study population. These findings suggest that earlier use of pedal access may decrease procedural time and fluoroscopy time without significant impact on limb outcomes.

In the current study, we focused on patients with specifically FP disease and further matched patients based on baseline demographic and lesion characteristics to control for significant variables that may have confounded previous results. While our overall cohort was small, this size is relatively large considering the previous reports on pedal access. In addition, we report not only 30-day but also 12-month outcomes, which show that retrograde crossing techniques do provide lasting benefits. With matching, we were able to show a significant difference in limb salvage in favor of retrograde crossing. Furthermore, despite our efforts at 1:1 matching based on the prioritization described herein, we were unable to match for presence of CTO, which suggests a higher degree of case complexity in the retrograde crossing group. While the exact etiology of improved limb salvage for retrograde crossing is unclear, we hypothesize that the improved limb salvage despite greater case complexity is secondary to reduced vessel trauma and perhaps less vessel injury at the distal re-entry site.

The retrograde crossing group had a significantly higher incidence of MI at 1 year (6.9% vs 0%; P=.04) (Table 3). This finding is most likely attributable to increased vascular disease burden as evidenced by a higher incidence of CAD and CTOs in the retrograde group and not the technique itself, since the periprocedural MI rate was not significantly different between the 2 groups (1.72% vs 0%, respectively; P=.32).

While we did assess proximal cap morphology to investigate whether a blunt or tapered CTO cap was associated with failure of an antegrade crossing technique, we did not find any significant difference between groups. This is most likely explained by inadequate power in the small cohort. Proximal cap morphology has been associated with antegrade crossing failure^9,10 and may contribute to prolonged procedure duration, site of percutaneous access, fluoroscopy duration, and cost. Further investigation into cap morphology in a matched or randomized manner would significantly contribute to treatment algorithms with pedal access.

Study limitations. Our study is limited by its retrospective and observational design. Indications for intervention and the techniques used for intervention were not standardized between operators, which could have introduced bias for which the matching could not account. Additionally, postprocedural patient characteristics such as smoking status and antithrombotic medication regimen were not evaluated, which could influence patency rates and limb salvage.

Conclusions

This retrospective, matched cohort study demonstrated that retrograde crossing of femoropopliteal occlusions was associated with decreased amputation rates after 1 year when compared with an antegrade crossing technique alone. The retrograde technique is safe, cost effective, and technically successful, and appears to be associated with improved short-term limb-salvage rates.

Acknowledgment. We acknowledge the University of Texas Southwestern Medical Center RED Cap and the Academic Information Systems teams for hosting and supporting the XLPAD multicenter registry.

Affiliations and Disclosures

From the ¹University of Texas Southwestern Medical Center, Dallas, Texas; ²Veterans Affairs North Texas Health Care System , Dallas, Texas; ³University of Denver, Denver, Colorado; ⁴Eastern Colorado Veterans Affairs Medical Center, Denver, Colorado; and ⁵St Marks School of Texas, Dallas, Texas.

Funding: REDCap: CTSA NIH Grant UL1-RR024982. Paul A. Harris, Robert Taylor, Robert Thielke, Jonathon Payne, Nathaniel Gonzalez, Jose G. Conde, Research electronic data capture (REDCap)  metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377-381. The XLPAD registry was supported with an institutional research grant from Boston Scientific Corporation.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Armstrong is a consultant for Abbott Vascular, Boston Scientific, Cardiovascular Systems, Inc, Gore, Medtronic, Philips, PQ Bypass, and Shockwave. Dr Alaiti reports income from Abbott Vascular, Abiomed, AngioSafe. Dr Banerjee reports income from Medtronic, Cordis, Livmor, Inc, Kaneka, and AstraZeneca. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript accepted September 15, 2022.

Address for correspondence: Shirling Tsai, MD, Division of Vascular and Endovascular Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, MC 9157, Dallas, TX 75390-9157. Email: shirling.tsai@utsouthwestern.edu

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