Hybrid treatment of multilevel revascularization in patients with peripheral arterial disease – a multi-centre study in Korea
Abstract
Abstract.Background: Endovascular treatment is an alternative first-line management for peripheral artery disease (PAD). Hybrid treatment (HT) is defined as a combined treatment for patients with PAD using endovascular and open surgery, simultaneously performed in an operating room. The results of HT are reportedly good for multilevel revascularization (MR) in patients with chronic limb ischaemia, and even in older high-risk patients. The goal of this study was to examine the clinical and haemodynamic outcomes of HT in patients who need MR. Patients and methods: Nine university hospitals in Korea participated in this multicentre study. A total of 134 patients with multilevel PAD underwent HT and MR. Patients were enrolled from July 2014 to June 2015 and were followed for 18 months. Results: The mean age of the patients was 68.8 ± 9.93 years and 88.1 % were men. Patients with Rutherford category 2 to 3 and 4 to 6 comprised 59.0 % and 42.0 % of the group, respectively. The technical success rate was 100 %. The primary patency rates at 12 and 18 months were 77.6 % and 63.9 %, respectively. The primary-assisted patency rates at 12 and 18 months were both 90.0 %. The pre-operative mean ankle brachial index (0.43 ± 0.23) increased to 0.87 ± 0.23 at six months post-operatively (t-test, p < 0.05). The amputation free survival rate was 97.1 %. Conclusions: Although outcomes of multilevel PAD are reportedly poor when endovascular treatment alone is used, we have shown that HT is a feasible alternative modality for patients with multilevel PAD, with satisfactory amputation-free survival and freedom from re-intervention rates.
Introduction
Peripheral arterial disease (PAD) is a highly prevalent atherosclerotic syndrome with an estimated worldwide incidence of approximately 200 million people [1, 2]. Approximately eight million Americans per year are diagnosed with PAD [3–5]. As PAD progresses, critical limb ischaemia (CLI) occurs as the final stage before limb loss. CLI is often a result of a multilevel disease leading to poor collateralization, which makes distal foot ischaemia worse than its less aggressive forms [6]. One treatment option for CLI is hybrid treatment (HT), which is defined as a combination of endovascular procedures and traditional open vascular surgery for multilevel revascularization (MR). It was first described in 1973 [7]. The reports suggest that 5–21 % of the total number of vascular reconstructions involve HT [8, 9]. Several authors [10–18] have demonstrated the efficacy and safety of HT for MR in patients with PAD. However, most studies [10–18] have assessed HT safety and efficacy for MR in patients with PAD using only single-centre studies with few patients.
Patients and methods
This study was a sub-analysis of HT for MR in patients with PAD, which analysed 134 consecutive patients with PAD who underwent HT for MR at nine vascular and endovascular centres at the University in South Korea between July 2014 and June 2015. This study was an independent, single-arm, multi-centre, retrospective analysis of a prospectively maintained database. All patients underwent computed tomography angiography (CTA) for the diagnosis of lower extremity arterial occlusive lesions. All lesions were categorized according to the Trans-Atlantic Inter-Society Consensus (TASC) II classification guidelines, published in 2007 [19].
Inclusion and exclusion criteria
Major inclusion criteria were 1) 18 years of age or older, 2) Rutherford classification category 2 to 6, 3) resting ankle brachial index (ABI) of < 0.9 or abnormal exercise ABI, and 4) a de novo lesion.
Major exclusion criteria were 1) procedures without combination of surgical and endovascular treatment, 2) previous vascular operation, 3) previous major amputation, 4) life expectancy < 1 year, 5) unsalvageable limb with extensive ischaemic ulceration or gangrene, and 6) acute limb ischaemia.
This study was approved by the Institutional Review Board of The Pusan National University Yangsan Hospital in Yangsan, Korea (IRB No. 05-2017-120).
Patient characteristics
Between July 2014 and June 2016, 134 patients (118 men; mean age 68.8 ± 9.3 years) with 343 multiple lesions were enrolled in this study. Most patients (81, 60.4 %) had hypertension, half of the patients (67, 50.0 %) had diabetes, and 25 (18.0 %) had coronary heart disease. The baseline characteristics of the patients and lesions are shown in Table I. Approximately 59.0 % of patients presented with claudication (Rutherford category 2–3) and 41.0 % with CLI (Rutherford category 4–6). Symptoms of rest pain were assessed in 13 patients (9.7 %) and 42 (31.3 %) had non-healing ulcers or gangrene, summarized in Table II. Out of 343 lesions, 134 patients were classified according to the TASC II classification. Among the 105 iliac lesions, there were five (4.5 %) TASC II A, 30 (28.5 %) TASC II B, 41 (39.0 %) TASC II C, and 29 (27.6 %) TASC II D lesions. Of the 177 (included 44 cases both leg involved). femoro-popliteal lesions, there were 15 (0.8 %) TASC II A, 40 (22.5 %) TASC II B, 73 (41.2 %) TASC II C, and 49 (27.6 %) TASC II D lesions, summarized in Table III. The BTK artery was non-patent in 61 patients. There were three (4.9 %) TASC II A, six (2.5 %) TASC II B, 22 (36.1 %) TASC II C, and 30 (49.1 %) TASC II D lesions.
Procedure
All HT procedures were performed by vascular surgeons in the operating room (OR) using fluoroscopy according to institutional standard practice under the precondition of systemic anticoagulation with heparin (100 U/kg) and provided that the anticoagulant state was not reversed until the end of the procedure.
Iliac lesions
Before the procedure, in cases where CT angiography revealed stenosis or an occlusion pattern above 70 %, the common femoral artery (CFA) and femoral bifurcation were exposed below the inguinal ligament in the OR. Puncture of the CFA was performed to establish guidewire access across the proximal iliac lesion. Conventional angiography through a femoral access showed total occlusion of the iliac lesion. A longitudinal arteriotomy was made and we performed endarterectomy with patch angioplasty. If thrombus in iliac lesions were detected, a thrombectomy with a 4–5 Fr Fogarty catheter under fluoroscopic guidance was performed. In patients with iliac lesions, iliac lesion crossing was attempted in a retrograde fashion, following the CFA dissection and exposure. When the abovementioned approach failed, the iliac lesion was crossed in a contralateral antegrade fashion. After having crossed the lesion, pre-dilatation by balloon was attempted followed by stent insertion. If all access procedures failed, open bypass surgery was performed, such as ilio-femoral, ilio-popliteal above knee or aorto-bifemoral bypass surgery.
Femoral lesions
In patients who required CFA endarterectomy and superficial femoral artery (SFA) intervention, the CFA lesion was initially opened at the groin, before the arteriotomy with patch angioplasty was performed. Bi-directional pre-arteriotomy guidewire access and endovascular therapy were attempted [14, 15]. Patients with failed endovascular treatment for a SFA lesion were considered for popliteal or tibial bypass surgery using a vein or polytetrafluoroethylene graft. Generally, anastomosis in healthy artery sites with a good run-off region, according to the angiography indicating the inflow and outflow, were targeted.
Below-the-knee lesions
All treatment decisions for below-the-knee (BTK) lesions, including percutaneous transluminal angioplasty (PTA), bypass surgery, endarterectomy or thrombectomy were made by the operator. Endovascular treatment is the treatment of choice at our institution. During PTA, the minimum balloon inflation time was two minutes, but longer inflation times of up to three to five minutes were generally preferred by the operators. If there were multiple BTK lesions to cover the full length of lesion, an overlap of at least 5 mm was ensured. For flow-limiting dissection, prolonged dilation was performed again. If angioplasty failed in BTK lesions, bypass surgery, endarterectomy, and thrombectomy were performed.
Post-operative surveillance
Multifocal revascularization was defined as involving at least two levels of revascularization (aorto-iliac, inguinal, femoropopliteal, or infrapopliteal). Technical success was defined at an angiographic evidence rate of 30 % of final residual stenosis of the target lesion after HT (including pre- and post-dilation stent placement and no procedure-related major adverse events prior to hospital discharge). Patients underwent surveillance at one, three, six, and 12 months post-procedure. At each visit, we assessed the Rutherford classification, TASC II classification, and patency. We checked ABI for six months and limb salvage rates CTA for 12 months, 24 months and development of symptom.
Patency rates were defined as primary (defined as patency of the target lesion during follow-up), primary-assisted (defined as patency of the target lesion following endovascular therapy at the target vessel site in case of symptomatic restenosis, but without occlusion at any time), and secondary (defined as patency of the target lesion after treatment for [re]occlusion, with patency ending with an untreated or surgically treated occlusion) [20, 21].
Loss of patency was defined as two instances in which ABI decreased by more than 0.15, unless the results of other examinations demonstrated significant stenosis. For iliac lesions, patients with a normal femoral pulse, without symptoms and without a decrease in ABI ≤ 0.15 were considered having patent iliac segments. Patients with a diminished femoral pulse, recurrent symptoms, and a decrease in ABI underwent arteriography. All patients who had MR also underwent duplex surveillance or CTA. Reinterventions were performed for maintaining patency or when clinically indicated.
Statistical analysis
Data were analysed using SPSS 19.0 software (SPSS, Inc., Chicago, IL, USA). Kaplan-Meier survival curves for primary patency, primary-assisted patency, secondary patency, and limb salvage were estimated. Continuous variables were presented as mean ± SD. Demographic comparisons were performed using Fisher’s exact test for categorical variables and the Mann-Whitney U test for continuous variables. A value of P < 0.05 indicated a statistically significant difference.
Results
Revascularization procedure
The most common procedure was common femoral endarterectomy (95 cases, 53.7 %), followed by SFA angioplasty (68 cases, 38.4 %) for femoral lesions, and iliac stenting (90 cases, 85.7 %) for iliac lesions. The procedures performed in HT are listed in Table IV. All components of the procedures were performed simultaneously and bypass surgery was performed, aorto-iliac in 105 (30.6 %) patients, femoro-popliteal in 177 (51.6 %) patients, and infrapopliteal in 61 (17.8 %) patients. Among the 134 patients who underwent HT, 61 (45.5 %) underwent endarterectomy and stenting/percutaneous transluminal angioplasty (PTA), 32 (23.9 %) bypass and stenting/PTA, 18 (13.4 %) underwent endarterectomy, bypass, and stenting/PTA, 19 (14.2 %) endarterectomy, thrombectomy, and stenting/PTA, one (0.7 %) bypass, thrombectomy, and stenting/PTA, and three (2.2 %) underwent endarterectomy, bypass, thrombectomy, and stenting/PTA, respectively. Procedural details for HT are shown in Table V.
Outcome on follow-up
The post-operative technical success rate was 100 % for HT. The mean pre-operative ABI of 0.43 ± 0.27 increased to 0.87 ± 0.23 after surgery and was sustained (0.87 ± 0.27) at the six-month follow-up (t-test, p < 0.05). The mean follow-up period was 18.2 ± 11.1 months (median, 18.2 months; range, 12–24.3 months). The primary, primary-assisted and secondary patency rates at the 12-month follow-up were 77.6 % ± 3.4 %, 90.0 % ± 2.4 %, and 95.6 % ± 4.5 %, respectively (Figure 1). The amputation-free survival rate was 97.1 %. There were four (3 %) major amputations, including two above the knee, two below the knee, and 32 minor amputations. There were no post-operative deaths. Nine patients had died by the 12-month follow-up. Six of them were following MI, and two patients, who had a previous diagnosis of heart disease (significant coronary artery disease and other comorbidities), died from heart failure. One patient had developed multiple system organ failure after reperfusion injury.
Discussion
A combination of endovascular and traditional vascular surgery was first reported in the 1970s [7]. In contrast to simultaneously performed HT, staged HT leads to longer hospital stays, higher costs, higher wound complication rates, and higher cardiac risk, due to performance of multiple procedures [9, 22]. Ebaugh et al. [9] reported that hybrid reconstructions increased by 7 % in a nationwide inpatient sample database between 2001 and 2004. Most cases underwent simultaneous hybrid procedures.
The HT can be performed in two different environments. The first environment, an operation room (OR), is ideal for open revascularization and is usually equipped with a mobile c-arm, which allows for digital subtract angiography with high resolution as well as road mapping and data backup. Although the image quality differs when obtained in the intervention suite, the sterility, illumination, and handling capabilities in the OR are central for performing HT. Five of our hospitals have an OR with a mobile c-arm. Another option is a special hybrid OR that is fully equipped for endovascular procedures, including excellent imaging tools; however, this option is more expensive. Four of our hospitals used hybrid ORs. Simultaneous HT is performed under fluoroscopy, allowing immediate verification of the procedural success, which in turn improves the results of the treatment.
Dosluoglu et al. [14] emphasized that obtaining inflow and/or outflow guidewire access before performing the arteriotomy is a key manoeuvre in HT. Many reports have explained the important technical aspects of the hybrid procedure. Piazza et al. [23], in their study of patients with iliac and femoral atherosclerosis, described a hybrid procedure that consisted of CFA endarterectomy and iliac stenting. In doing so, they describe it as an effective procedure for surgical revascularization for ilio-femoral atherosclerotic disease. Dosluoglu et al. [8] classified HTs as either simple (sHYBRID group) or complex (cHYBRID group). When lesions with a TASC II classification of A/B were treated with endovascular treatment, they were categorized as the simple hybrid group. The role of femoral endarterectomy is important in cHYBRID repairs. Higher rates of morbidity and mortality were noted in the complex (cHYBRID) group, possibly due to the higher-risk nature of these patients.
Some vascular surgeons in our group have reported slight differences regarding specific surgical techniques in their single-centre HT results [16–18, 24]. To our knowledge, this is the first multi-centre study with more than 100 cases performed by the Korean Society for Vascular Surgery. Similar to other recently published series [11, 16–17], femoral endarterectomy (95/134 cases) was a key component of hybrid revascularization in our group series. The early mortality rate was 3.1 %. In addition, brachial access, or multiple accesses (contralateral femoral and transbrachial) is not uncommon in these patients. We classified bypass surgeries (63 cases) based on the anatomical lesions: aorto-bifemoral (one case), ilio-popliteal (one case), femoro-femoro contralateral (10 cases), femoro-popliteal (44 cases), femoro-BTK (four cases), and popliteal-BTK (three cases). All HTs were performed according to institutional standard practice in different style hybrid ORs. We reached a 100 % technical success rate.
Zhou et al. [13] reported primary patency rates, primary-assisted patency rates, and secondary patency rates of 72.2 %, 83.3 %, and 94.4 %, respectively, with a mean follow-up duration of 24 months for patients with multifocal ilio-femoral occlusive disease who underwent simultaneous iliac artery stenting and open femoral endarterectomy. Cotroneo et al. [10] reported two-year results of hybrid revascularization in their study and the primary patency rate was 86.2 % at six months and 79.1 % at 24 months, with a technical success rate of 100 %. Dosluoglu et al. [8] reported results of their hybrid procedures with an immediate technical success rate of 96 % for cHYBRID and 100 % for sHYBRID procedures. The 12- and 36-month primary patency rates in sHYBRID patients who had undergone aorto-iliac level interventions were 80 % and 75 %, respectively. These rates were similar to those in the cHYBRID group, which were 87 % and 81 %, respectively (P = 0.863). Limb salvage rates at 12 and 36 months in patients with CLI were similar in the endovascular, sHYBRID, and open groups (86 % and 80 %, 94 % and 80 %, and 80 % and 74 %, respectively); however, these rates were improved in the cHYBRID group (100 %; P = 0.014). Granjean et al. [25] reported European results with a technical success rate of 100 %. The primary, primary-assisted and secondary patency rates at one year were 39 %, 66 %, and 81 %, respectively. The limb-salvage rate was 94 %. Our rates were similar or relatively higher to those reported in other studies. In our study, the initial technical success was 100 % and the primary, primary–assisted, and secondary patency rates at 12 months were 77.6 % ± 3.4 %, 90.0 % ± 2.4 %, and 95.6 % ± 4.5 %, respectively. The morbidity and mortality rates in our patients who underwent HT were lower than those reported in other studies, although the differences were not statistically significant [17]. Eight of the nine mortalities in this group occurred in patients with poor functional capacity, all of whom had significant MI (six patients) or heart failure (two patients), and only one patient died as a result of the procedure, related to reperfusion syndrome.
Performing HT may greatly reduce hospital charges and the length of stay (LOS). Ebaugh et al. [9] evaluated the costs of staged versus simultaneous lower extremity arterial HT. Notably, the unadjusted results showed that hospital charges and LOS more than doubled, if staged rather than simultaneous hybrid procedures were performed.
Patients with CLI and MR are frequently elderly and frail with high mortality rates. Taking this into account, we believe that simultaneous HT is a feasible and effective treatment for patients with CLI with multifocal high-risk atherosclerotic disease.
Limitations
This study had several limitations. First, this was a retrospective study, which may have created potential selection and information bias. Second, the relatively short follow-up period and low incidence of adverse events and mortality may have affected the reliability of our results. Third, the MR techniques were not standardized. An international multi-centre prospective study using standardized techniques as well as a comparison of hybrid and pure bypass surgery are needed in the future. Finally, the lack of control or comparison group data, including open surgical bypass data, may prevent any conclusive analysis of HT.
Conclusions
HT procedures are effective for patients with multilevel PAD, as they exhibit good patency and limb salvage rates. For successful hybrid surgery, the role of femoral endarterectomy should be emphasized. An HT should be considered for patients with CLI and high surgical risk. Vascular surgeons also need to master several types of HT for patients requiring MR.
Acknowledgements
This work was supported by a grant from the Korean Vascular Society.
There are no conflicts of interest existing.
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