Objective: Multilevel chronic total occlusion (CTO) is the biggest challenge in endovascular revascularization with a high rate of treatment failure due to inability to cross the lesion when utilizing single access. Few limited prior studies have shown that dual access can increase the success rate in peripheral CTOs. The purpose of this study was to evaluate the efficacy and safety of initial dual antegrade and retrograde access approach compared with single antegrade or retrograde approach for crossing any level of CTO.
Methods: A retrospective analysis was conducted of patients who had at least one lower extremity CTO treated by a single operator at a community hospital between 2013 and 2018. The primary endpoint was crossing and treatment success. Patient and procedural demographics were collected and analyzed to determine variables of treatment success and failure. Propensity score-matched (PSM) analysis was performed to address baseline differences.
Results: A total of 141 patients were included, with 88 in the single access cohort and 53 in the dual access cohort. Crossing success in the dual access cohorts and single access cohorts were 92.5% and 73.6%, respectively (P = .010). Dual access was a very strong indicator of crossing success (P <.001 all participants, and P =.001 PSM analysis) and going subintimal was an indicator of failure (P <.001 all participants, and P =.001 PSM analysis). There was a low rate of complications with no statistical difference between the two cohorts.
Conclusions: This single center study demonstrated that dual antegrade and retrograde access technique significantly increases the success of CTO crossing versus single access in complex peripheral artery disease patients.
Key words: dual access, chronic total occlusion, critical limb ischemia, peripheral artery disease
Peripheral arterial disease (PAD) is an undertreated and debilitating illness affecting 8.5 million Americans and is associated with excessively high rates of morbidity and mortality.1,2 It is the leading cause of amputation, with more than 150,000 amputations occurring each year in the United States.3,4 Critical limb ischemia (CLI) is the worst form of PAD, as there is a 20% mortality within 6 months of diagnosis and 20% of patients receive an amputation within one year.5,6 Revascularization is essential to improve symptoms, heal wounds, and ultimately prevent amputation.7
The biggest challenge in endovascular revascularization is chronic total occlusion (CTO). CTOs account for up to 40% to 50% of lesions in PAD and have high treatment failure rates (20% to 40%), due to inability to cross the lesion into the true lumen.8–10 Interventionalists are increasingly opting for an endovascular first approach, especially in high-risk CLI patients, as studies have demonstrated similar outcomes to surgery.5,11 For this reason, it is vital to adopt advanced techniques in order to improve crossing and treatment success.
Traditionally, the most common endovascular approach is the contralateral retrograde “up and over,” which carries a 20% failure rate, even when undertaken by skilled operators.12 This approach is limited by decreased torquability, pushability, and reach of equipment. Recently, alternative retrograde access utilization has gained popularity and demonstrated excellent safety and efficacy.10 However, the combination of the antegrade and retrograde approach has not been widely studied or described in literature.13–15
Using dual antegrade and retrograde approach in coronary CTO intervention has boosted success from 50% to 70% to over 90% and has been incorporated into treatment algorithms.16–18 With such great success in the coronary bed, we think that combining antegrade and retrograde access can increase crossing success in peripheral CTOs.
The purpose of this study was to evaluate the efficacy and safety of utilizing dual antegrade and retrograde access approach for crossing peripheral CTOs.
A retrospective review of all patients who had at least one CTO of the lower extremity with endovascular intervention by a single operator was performed from August 2013 to January 2018 at a community hospital. Central institutional review board approval was obtained, and informed consent was waived. The study included 141 patients (95 males, 46 females). Patients were categorized into two cohorts: (1), single access (single antegrade or retrograde access approach, n=88) and (2), dual access (dual antegrade and retrograde access approach, n=53). All patients had Rutherford class (RC) 3-6 manifestations.19 Data collection included baseline participant demographics, relevant medical history, and procedural characteristics.
The patients were treated according to the standards of care at the institution and per the physician preference. Depending on the location of percutaneous access being achieved, the patient was placed in either supine, prone, or reversed position. All alternative access was achieved using ultrasound or fluoroscopic guidance. Each patient received local and conscious sedation. Anticoagulation was accomplished using weight-based doses of heparin to achieve a therapeutic activated clotting time between 250 to 300 seconds. Access sites consisted of femoral, popliteal, tibiopedal, and brachial. The CTOs were located in the iliac, femoropopliteal, or infrapopliteal vessels, which include the tibioperoneal trunk, anterior tibial, peroneal, and posterior tibial. Crossing direction was classified as antegrade, retrograde, or both. Intimal and subintimal crossing was documented as well if a wire or crossing device went subintimal at any point during the procedure.
Study Definitions and Endpoints
Technical crossing success was defined as the ability to deliver a wire through the entirety of the CTO into the true lumen and subsequently pass a catheter or balloon for revascularization. Documented complications included minor and major hematoma, perforation, retroperitoneal bleed, pseudoaneurysm, acute kidney injury, blood transfusion, and in-hospital death. Patient and procedural demographics were evaluated to identify factors that influence CTO crossing success or failure.
SPSS (version 25; IMB SPSS) and XLSTAT (2018; Data Analysis and Statistical Solution for Microsoft Excel.) software were used for data collection and statistical analysis. Values presented are n (%) or mean ± standard deviation. P-values for quantitative variables are from the Mann-Whitney U test. P-values for qualitative variables are from the Chi-square test or the Fisher exact test (if theoretical frequencies were <5). Propensity score-matched (PSM) analysis was also utilized to optimize the balance of baseline demographics and lesion characteristics. The significantly different baseline variables (hyperlipidemia, wound present, prior amputation, prior treatment type, CTO vessel location, and CTO amount) were entered in a 1:1 matching model utilizing the optimal algorithm of Mahalanobis distance with a tolerance of 0.001, caliper of 0.10, and confidence interval of 95%. In addition, logistic regression multivariable analyses for predictors of CTO crossing success were conducted on all participants and the propensity score-matched participants. A forward stepwise model selection was utilized with a Likelihood ratio criterion and a probability for entry and removal in the multivariable model of 0.1 and 0.2, respectively. The overall classic logistic model was set to a tolerance of 0.001, confidence interval of 95%, stop conditions of 100 iterations, a convergence of 0.000001, and a constraint of a1=0. Variables included in the multivariable model are indicated by the asterisks in the baseline and procedural tables of the results section.
The baseline subject demographics (Table 1) and CTO lesion characteristics (Table 2) are presented for all participants (88 single access vs 53 dual access) and the PSM participants (53 single access vs 53 dual access). There was a statistical balance of baseline variables after 1:1 PSM except for history of coronary artery disease (CAD) and treatment history, which indicated higher rates for the dual access participants (Table 1). Overall, there was a high percentage of patients with CLI (RC 4-6), diabetes, hypertension, hyperlipidemia, and a history of smoking and CAD (Table 1). After 1:1 matching there was a statistical balance of CTO lesions between the single access and dual access cohorts, with a similar average number of CTOs and lesion length (Table 2).
The most common form of dual access was via the combination of the common femoral artery (CFA) and the infrapopliteal artery (Table 3). Utilization of dual access versus single access resulted in a significantly higher percentage of retrograde CTO crossing and a significantly higher rate of going subintimal at any time (Table 4). The Glidewire Advantage/Quick-Cross (Terumo, Spectranetics) was utilized in 52.8% of the dual access subjects, and orbital atherectomy was the most common form of vessel preparation (26.4%). There was a significantly higher rate of CTO crossing success for the dual access participants (Table 4). Lastly, the rates of complications were low with no statistical difference between the two cohorts.
A multivariable analysis was conducted to determine the predictors of CTO crossing success (Table 5). Variables included in the model are indicated by asterisks in Tables 1 to 4. The multivariable model AUC (c-statistic) for all participants (n=141) and PSM participants (n=106) was 0.842 and 0.821, respectively. After matching, utilization of dual access remained as a positive predictor of CTO crossing success (odds ratio, 13.5, P =.001), whereas going subintimal at any time continued to indicate a negative impact on CTO crossing success (odds ratio 0.084, P =.001).
Our study indicates that utilizing dual antegrade and retrograde access for the endovascular treatment of peripheral CTOs has a higher chance of crossing success and revascularization compared with single antegrade or retrograde access. The uniqueness of our study is that it included all-comers with CTOs at different vascular levels. The few other studies available were constrained by specific access sites and CTO locations.20–22 The patient population had significant comorbidities and included RC 4-6, which are typically excluded from large trials.23 In our study, even with the complex real-world patient population, successful outcomes were produced, often in one procedural setting, by implementing dual access. We believe that this is translatable and reproducible for endovascular procedural success.
The access sites were decided by the interventionalist prior to the procedure, based on a combination of physical examination, prior arterial Doppler studies, computed tomography angiography, and prior invasive angiogram if available. Before the start of the procedure, the dual access patients were prepared for both probable access sites. Upon initial angiography, the proximal and distal cap morphology was studied and the decision for antegrade or retrograde approach was decided from that assessment.
Proximal iliac CTOs can be difficult, as the contralateral “up and over” strategy does not always give adequate support. We used the brachial approach for crossing iliac CTOs in an antegrade fashion with the placement of a 90 cm sheath to improve pushability and support. Femoropopliteal CTOs can be approached by retrograde CFA and popliteal or infrapopliteal access.
These procedures were performed by an early career interventional cardiologist fewer than 5 years into interventional practice. During the initial years, the failure rate of CTO revascularization was 34%. This high rate of failure led to a dedicated change in practice with the implementation of the dual access approach for CTO cases, which was adopted from successful CTO revascularization in coronary arteries. These changes subsequently led to higher success rates.
Compared with the coronaries, peripheral CTOs present unique challenges as they occur on multiple vascular levels and at longer lengths but offer more options for access for a more direct engagement of the lesion. If a patient has multiple CTOs, it is important to open the first CTO to get access to the second CTO. Dual access could help approach the CTOs from both directions, and it increased the success rate in situations with more than one CTO. In cases of long lesions, dual access can provide options of treating the lesions from both the antegrade and retrograde route after crossing, which could potentially decrease the procedural time and radiation exposure.
Most interventionalists do not attempt retrograde access unless a traditional antegrade attempt fails. This could stem from the fear of compromising the last patent outflow vessel and doubling vascular complications. A recent study published by Saab et al characterized CTO cap morphology and proposed an algorithm for crossing CTOs.24 Type II (concave proximal cap and convex distal cap) and Type III (convex proximal cap and concave distal cap) caps are recommended to be approached with dual access. Taking this into account, traditional single access would be insufficient to cross a significant portion of CTOs. Severely calcified and long fibrotic lesions need the incorporation of dual access and advanced crossing techniques for successful crossing.
We present 3 case examples utilizing the dual access approach for CTO crossing in each lower extremity vascular level.
Figure 1 demonstrates a long CTO of the distal superficial femoral artery extending through the entire popliteal artery into the tibioperoneal trunk. There is a large collateral extending from the proximal cap. Because of this, the antegrade approach proved to be unfavorable as wires and catheters directed into the collateral instead of the vessel lumen. Retrograde access was achieved in the posterior tibial artery, and the entirety of the lesion was crossed. Successful treatment with atherectomy and drug-coated balloon demonstrated excellent results with rapid inflow.
Figure 2 shows a long CTO of the anterior tibial artery. Antegrade femoral and retrograde anterior tibial access was obtained. A wire and support catheter crossed the lesion through the retrograde sheath, and the wire was externalized for subsequent treatment. Atherectomy, angioplasty, and a drug-eluting stent demonstrated excellent outflow.
Figure 3 shows a flush occlusion of the right common and external iliac artery. Antegrade access was achieved in the left brachial and retrograde access in the right common femoral artery. The lesion was partially crossed from the antegrade direction and the remainder of the lesion from the retrograde direction. Subsequent angioplasty and stents demonstrated excellent flow.
The technique of dual antegrade and retrograde access significantly increases the rate of CTO crossing success in patients with complex PAD. Proper planning and optimal access sites are required for the success of this combination strategy. We believe this could have a major impact on successfully reducing the amputation rates.
This was a nonrandomized, observational, single-center, retrospective study of procedural/index outcomes only. This study was not powered due to the limited sample size. Patient selection may be operator dependent, so the results may not be generalizable outside this observational study.
Bailey Ann Estes and Joji J. Varghese have nothing to disclose. Brad J. Martinsen and Zsuzsanna Igyarto are employees of Cardiovascular Systems, Inc. Jihad A. Mustapha has a consulting agreement with Cardiovascular Systems, Inc and is a consultant to Bard Peripheral Vascular, Boston Scientific, Medtronic, Terumo, and Phillips.
Manuscript submitted October 30, 2018 and accepted December 27, 2018.
Address for correspondence: Joji J. Varghese, MD, FACC, FSCAI, Hendrick Medical Center 1900 Pine Street, Abilene, Texas 79601, Email: firstname.lastname@example.org
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