Mid-Term Results of Subintimal Angioplasty for Critical Limb Ischemia: 5-Year Outcomes

Abstract

Objective. Compare effectiveness of subintimal angioplasty versus bypass surgery for TASC C and D femoropopliteal lesions. Methods. Of 1076 patients referred with pulmonary vascular disease from 2002 to 2007, 206 SIAs in 190 patients and 128 bypass grafts in 119 patients were studied. All patients had rest pain and/or tissue loss. Primary endpoints were amputation-free survival (AFS) and sustained clinical improvement. Secondary endpoints were major adverse events (MAE), binary restenosis rate, freedom from target lesion revascularization (TLR), and a special quality-adjusted life year (QALY) endpoint (Q-TWiST) that incorporated both length and quality of life. Results. At 5 years, clinical improvement was sustained in 82.8% of the SIA group versus 68.2% of the BS patients (p = 0.106). Five-year all-cause survival was similar for SIA (78.6%) and BS (80.1%; p = 0.734), as was AFS (SIA 72.9% versus BS 71.2%; p = 0.976). Hyperfibrinogenemia (p = 0.009) and C-reactive protein (p = 0.019) had negative effects on AFS. Five-year freedom from binary restenosis was 72.8% for SIA versus 65.3% for BS (p = 0.700). While the 5-year freedom from TLR rates (SIA 85.9% versus BS 72.1%, p = 0.262) was not statistically significant, the risk of MAE (p < 0.002) and length of hospital stay (p < 0.0001) were significantly reduced. Q-TWiST significantly improved (p < 0.001) and cost-per-QALY was reduced with SIA. The 5-year risk of reintervention (p > 0.05) and mean number of procedures (p = 0.078) were similar. Conclusion. Five-year freedom from MAE was enhanced by 20% in the SIA group, with substantial cost reduction and better Q-TWiST. SIA is a minimally invasive technique that expands amputation-free and symptom-free survival.

VASCULAR DISEASE MANAGEMENT 2011;8(9):E155–E163

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Introduction

Although there are global enhancements in quality of life for the general elderly population, patients with peripheral vascular disease and CLI face a gloomy future and have a shoddier quality of life than their peers.¹ CLI bears a dismal prognosis with mortality estimates of 30% for the first year, and if left untreated, the 5-year mortality rate is up to 70%.^1–4 In the context of such poor long-term survival, infrapopliteal bypass surgery is a demanding, minimally invasive, and cost effective endovascular procedure that is easy to perform and has equivalent results to traditional surgery.

Perfection in vascular surgical techniques with enhancement in endovascular maneuvers revolutionized CLI management.⁵ In light of advancements over the past 10 years, historical studies, chronological TASC classifications, and results no longer apply to contemporary CLI management protocols. A belligerent forceful strategy in CLI management is vindicated on health economic grounds as long as technical and clinical outcomes are over 75%. However literature appraisal revealed that only 19% of patients have an uncomplicated infrainguinal reconstruction.^1,4 

Quality of time spent without the symptoms of disease or its toxicity is the ultimate contrivance in gauging an intervention. There are bundles of variables in old population groups that the traditional health-related quality of life cannot chronicle, nor can they perceive the transformations that individual patients may encounter.

Our primary aim is to equate effectiveness of SIA with BS in sustaining clinical improvement and amputation-free survival (AFS). Secondary endpoints are binary restenosis rate, freedom from target lesion revascularization (TLR), risk of major clinical adverse events (MCAE), quality time without symptoms of disease or toxicity of treatment (Q-TWiST), and cost-effectiveness.

Patients and Methods

From 2002–2007, 1076 patients were referred with peripheral vascular disease (PVD). Clinical, procedural, imaging, and follow-up data are routinely entered and prospectively maintained in our VascuBase^™ system (Consensus Medical, Vancouver, Canada). Using this system we performed a prospective observational parallel group comparison of 334 primary procedures (SIA = 206, BS = 128) in 309 CLI patients (NSIA = 190, NBS = 119) with TASC C and D lesions.

Patient Demographics

Mean age (SIA 73±13 yrs vs. BS 70±14 yrs, p = 0.127), and comorbidity severity scores (p > 0.05) were similar between groups. Females in the SIA group comprised 55% vs. 35% in BS, p = 0.0005 (Table 1).

Lesion Characteristics

All patients had critical limb ischemia (Rutherford Category 4–6)⁶ with TASC C or D lesions (TASC II)¹ and all lesions were de novo rather than recurrent. There was no significant difference between the groups regarding lesion length, inflow, or run-off (p > 0.05) (Table 2).

Imaging

All preoperative and follow-up imaging was done with B-mode and color duplex ultrasound scanning using the Philips iu22 (Philips Medical Systems, Andover, Massachusetts). Binary restenosis rate was greater than 50% reduction in vessel diameter, equivalent to a peak systolic velocity (PSV) ratio of > 2.4 across the target lesion. Ankle brachial indices (ABIs) and toe pressures (TP) were measured on the flow lab (Parks Medical Electronics, Inc., Aloha, Oregon). All patients had resting ankle pressures (AP) < 40 mmHg and TP < 30 mmHg in the presence of rest pain or an AP < 60 mmHg and TP< 40 mmHg if they had tissue loss.⁶

Indications for surgical intervention included presence of an echolucent plaque as visualized on duplex scan and the absence of a ‘nipple’ between the plaque and vessel wall, which rendered the lesion unsuitable for SIA. An echolucent plaque means the lesion is too soft for subintimal dissection and in danger of embolizing. The absence of a nipple or a flush occlusion makes it difficult to initiate the subintimal dissection plane. In addition, if treating a flush occlusion at the origin of the SFA, the origin of the profunda femoral artery may be compromised either by dissection or the subsequent balloon angioplasty. All patients are brought to theatre on an intention to treat basis.⁷

Procedural Specifications

All SIA procedures were performed in theatre using the OEC 9800 mobile C-arm imaging system (GE Healthcare, Waukesha, Wisconsin). All primary endovascular procedures were performed percutaneously. In the case of previous groin surgery, the patient had a mini transverse groin incision and femoral artery visualization. Fifteen percent of cases were done using the contralateral ‘up-and-over’ coronary approach with a Vanshee 3 cathether, Amplatz Superstiff 0.035” wire, and a 7 Fr Balkin Tip sheath (Cook Medical, Bloomington, Indiana). In the remaining cases we used 6 Fr introducer sheaths (Johnson & Johnson, Warren, New Jersey), Terumo 0.035” curved, straight or Bolia tipped guidewires (Terumo, Somerset, New Jersey) with Pier and Van Andel catheters (Cook Medical) were used for subintimal dissection. In the case of dissection, perforation, elastic recoil, or residual stenosis > 30% despite prolonged balloon inflation, SMART (Cordis Corporation, Warren, New Jersey) or Complete SE (Medtronic, Santa Rosa, California) nitinol self-expanding stents were used in the SFA and the Lifestent^® (Bard Peripheral Vascular, Inc., Tempe, Arizona) was deployed in the popliteal with the knee bent during deployment (Figure 1).

Adjuvant Pharmacotherapy

Adequate pain management, control of any infection, prevention of thrombosis progression, and optimization of cardiac and respiratory function were instituted while simultaneously establishing the full precise morphology of peripheral arterial disease.⁸

All SIA patients had perioperative N-acetylcysteine and normal saline infusion (1.5ml/kg/hr) to minimize the risk of contrast-induced nephropathy. Every patient in the study had adjuvant pharmacological treatment in the form of aspirin, pravastatin combined with a cardio-selective beta-blocker, and/or a calcium-channel blocker. These were commenced preoperatively and continued postoperatively with the addition of clopidogrel with the aim of reducing early failures due to thrombosis, intermediate graft occlusions due to intimal hyperplasia, or further progression of atherosclerosis. 

Follow-up

Follow-up was performed in the immediate postoperative period, at 6 weeks postoperatively, at 6-month intervals for the first 2 years, and yearly thereafter. The follow-up protocol consisted of interval history (new symptoms) and examination and measurement of ABIs and duplex scanning of the entire length of the target lesion or graft. Peak systolic velocities and the velocity ratios were calculated across all identified lesions. A PSV ratio > 2.4 together with a drop in ABI of > 0.15, in the presence of a deterioration in clinical status, was taken as an indication for re-intervention.^6,9

Clinical Improvement

• Perioperative morbidity and mortality rates were compared between groups for the period of hospitalization for the primary procedure. 
• Amputation-free survival: Kaplan-Meier analysis was used to calculate long-term survival and the cumulative endpoint of amputation-free survival and the curves for SIA and bypass were compared by log rank analysis. Only amputations above the level of the mid-forefoot were counted as major amputations. Minor amputations were considered to be of little handicap and often, only the best that could possibly be achieved in patients who presented with gangrene of the digits. 
• Sustained clinical improvement was defined as a persistent upward shift of at least 2 Rutherford categories and/or hemodynamic improvement (ABI > 0.15) without the need for repeated TLR in surviving patients. Relief of rest pain, which is essentially a purely subjective phenomenon, was defined for the purposes of this study as “complete relief of pain without the use of any analgesics.” Only patients with flat surface or transdermal ulcers were admitted to the trial, and ischemic cracks between the toes or on the heel were not used as measurable endpoints. Total ulcer healing was taken as the primary endpoint, rather than merely a tendency to healing or reduction in ulcer size.  

Procedural Outcome

A distinction was made between clinical success, which applied to the whole limb and binary restenosis, which applied to the revascularized or bypassed segment only.

• Endovascular technical success was defined as successful access and deployment of the device and 30% diameter residual stenosis after revascularization.
• Binary restenosis rate was assessed by duplex ultrasound and is defined as a peak velocity ratio of < 2.4 at the target lesion and was calculated using Kaplan-Meier survival curves. 
• Freedom from repeated target lesion revascularization (TLR) was defined as endovascular or surgical target lesion redo-procedures in surviving patients with preserved limb and was calculated using Kaplan-Meier survival analysis.

Quality of Life Assessment

A special quality-adjusted life year (QALY) endpoint, which incorporates both length and quality of life, was used to evaluate treatments. TWiST (time spent without symptoms of disease and toxicity of treatment)¹⁰ was useful for solving the dilemma of treatment selection if sustained clinical improvement and/or amputation-free survival differences were statistically significant but overall survival differences were not, since it deals with the fact that extensions to disease-free time may be at the expense of treatment toxicity.

The Q-TWiST endpoint was used as a natural extension of the quality-of-life oriented endpoint TWiST. Q-TWiST is an adaptation of the concept of QALY and the methodology was extended so that periods spent with toxicity or relapses were included in the analysis but weighted to represent their quality value relative to TWiST. Thus, overall survival was scaled down by arbitrarily giving survival during treatment or symptoms a reduced value. Utility values for both SIA and bypass surgery were based on values previously derived using a Markov decision analysis model.¹¹

Due to the risk of informative censoring and of biased Kaplan–Meier estimates of the survival function, we performed partitioned survival analysis.¹⁷ Overall survival was partitioned into the time spent in each health state, (i.e., time spent without symptoms or toxicity from treatment was separated from time spent with toxicity of treatment and time spent with secondary intervention). The mean duration in each state for each group was combined as a weighted sum according to the Q-TWiST model. Weighting the time spent in each health state at the group level rather that at the individual level avoided the need to weight censored survival times and thus overcame the problem of informative censoring.

The upper time limit for the analysis, 60 months, was based on the follow-up time of the study cohort and was chosen to reduce censoring.

Cost

The total costs per procedure, inclusive of follow-up, were calculated in order to estimate the cost per QALY gained and the incremental cost-effectiveness ratio (ICER) of an SIA program relative to the standard bypass surgery program. In-patient hospital expenses are shown in Table 3.

Results

Clinical Improvement
Morbidity and Mortality

Perioperative mortality was more than halved with SIA compared to BS (1.6% vs 3.4%, p = 0.317) despite a lack of statistical significance. The significant reduction in perioperative morbidity is reflected in the sizeable reduction in hospital stay following SIA compared to BS (14±16 days vs. 24±23 days, p < 0.0001). By 5 years, SIA patients continued to show sustained freedom from major adverse clinical events, such as death, limb loss, myocardial infarction, or stroke (68% vs 57%, p < 0.002) despite no significant difference in all-cause survival (SIA (78.6%) vs. BS (80.1%), p = 0.734, h = 1.10, 95% CI = [0.65–1.87]).

Amputation-Free Survival

After 5 years there was no difference in the number of patients surviving without the need for major amputation (above-knee or below-knee) regardless of whether they had primary SIA 72.9% or whether they had BS as their primary procedure 71.2% (p = 0.9765) (Figure 1). A Cox-proportional hazard ratio was performed to determine the factors related to adverse prognosis for amputation-free survival. We found that hyperfibrinogenemia (serum fibrinogen > 3.6g/L) significantly increased the risk of death and/or amputation at 5 years (p = 0.009, risk ratio (RR) = 2.4, 95% CI = [1.4–4.6]). Elevated CRP (> 5mg/L) had an adverse prognostic effect (p = 0.019, RR = 1.02, 95% CI = [1.01–1.04]).

Elevated HbA1C (> 6.0%) was not prognostic (p = 0.603, RR = 1.13, 95% CI = [0.73-1.73]), nor was hyperhomocystinemia (serum homocysteine > 13.9 µmol/L) (p = 0.524, RR = 0.88, 95% CI = [0.54–1.44]).

Sustained Clinical Improvement

Over a 5-year period, 82.8% of patients who had primary SIA showed sustained clinical improvement of at least Rutherford categories and maintained an improvement in ABI of at least 0.15 without the need for target lesion revascularization. This was similar to the sustained clinical improvement rate seen with BS (68.2%, p = 0.106, h = 0.65, 95% CI = [0.38-1.11]) (Figure 2).

Procedural Outcome
Technical Success

Residual stenosis was less than 30% in all cases of SIA. There was no failure of re-entry; the Outback re-entry device (Cordis Corporation, Warren, New Jersey) was used in one case and intravenous ultrasound was used in 2 cases. Nitinol self-expanding stents were used in 35% of cases with a mean number of 1.3 stents in those that were stented. 

Once we could enter the subintimal plane we were able to re-enter the true lumen in all cases. However there was one instance in which a diabetic man had an initial attempt at SIA; the superficial femoral artery was completely occluded and the lesion was too calcified to pass a guidewire into the subintimal plane. This was the only case in which we needed to convert on-table to a bypass procedure, giving a technical success rate of 99.5%.

The autologous vein was used in 60% of cases and Dynaflo ringed PTFE grafts (Bard Peripheral Vascular, Inc., Tempe, Arizona) were used in the remaining cases. Prosthetic grafts were only used in above knee bypass procedures when no suitable leg or arm vein was available. Technical success for bypass was 100%.

Binary Restenosis Rate

At 5 years freedom from binary restenosis, duplex ultrasound (PSV ratio < 2.4) was statistically similar between SIA (72.8%) and standard BS (65.3%) (p = 0.700, h = 1.10 [95% CI =  0.69 to 1.74]) (Figure 3).

Cox proportional analysis showed that hyperhomocystinemia was an adverse prognostic indicator for the risk of binary restenosis at 5 years for both SIA (p = 0.008) and BS (p = 0.019) (Table 4).

The use of a stent (35%) did not impact on the risk of binary restenosis at 5 years (p = 0.780, RR = 1.10, 95% CI = [-0.53 to 1.59]. Similarly the mean number of stents used (1.3) were not prognostic indicators of the risk of restenosis (p = 0.330, RR = 1.69, 95% CI = [0.59 to 1.49].

Freedom from Target Lesion Revascularization

Five-year freedom from TLR for SIA (85.9%) was improved, albeit nonsignificantly, when compared to BS (72.1%), (p = 0.2624, h = 0.71, 95% CI = [0.39–1.30]), with a nonsignificant reduction in the mean number of procedures in the SIA group compared to the BS group (SIA 1.19±0.50 vs. BS is 1.10±0.41, p = 0.078) (Figure 4).

Quality of Life Analysis

Over a 5-year follow-up period the Q-TWiST (Table 5) was 24.7 months for SIA versus 24.5 months for BS. Sensitivity analysis showed that Q-TWIST was significantly improved with SIA compared to BS over a full range of utility values between 0 and 1 (p < 0.0032).

Cost per Quality Adjusted Life Years

Over a 6-year period (2001–2007) we treated 128 critically ischemic limbs with BS at a total in-patient cost of €2,185,091.63 ($3,157,455 USD). We treated 78 extra patients with SIA and it cost  €77,512.32 ($112,005 USD) less if we include the cost of 5 years follow-up and repeat procedures, mean cost per primary procedure was €11,655.90 ($16,842 USD) for SIA and €18,726.05 ($27,059 USD) for OR. This meant that the savings per primary procedure is €7,070.15 ($10,216 USD) if treated with SIA rather than BS.

The greatest savings were made in the SIA group by reduced length of hospital stay, including readmissions, and enhanced patient turnover rates with more efficient use of theatre time.

SIA cost €5,662.79 ($8182 USD) per QALY. This is €3,509.15 ($5070 USD) cheaper per QALY than BS, giving an incremental cost-effectiveness ratio (ICER) of SIA vs BS of €10,768.20 ($15,560 USD) per QALY gained (Table 3).

Discussion

Contemporary studies on lower limb endovascular therapy are relatively sparse and those available primarily focused on technical and clinical outcomes. Consequently there is a paucity of data on either quality of life or cost-effectiveness, which seems somewhat remiss especially in a population overburdened with comorbidities and a limited life-expectancy, and when the line between risks and benefits is obscure. As objective indicators of technical efficacy and clinical outcome, binary restenosis rates and target vessel revascularization rates serve a role for contextualizing studies and need to be reported in standard format to allow for interstudy comparisons. However, on a day-to-day basis they add little in practical terms and they should not be examined in isolation without addressing the issues of functional capacity, quality of life, and cost-effectiveness.

This is a unique study as all patients were enrolled because of CLI with either tissue loss, gangrene, or rest pain. All patients followed our protocol for assignment to their most suitable lesion; 82% of all patients in both groups were matched for their length of occlusion and tibial runoff vessel. As a reflection of the minimal-invasiveness that was necessary to treat such a high comorbid population we used duplex ultrasound as our sole preoperative imaging technique in 90% of patients. Sultan et al have previously demonstrated this to be an accurate and sensitive tool, which requires very minimal supplementation with alternative imaging modalities, especially in the femoropopliteal segment where the limitations posed by calcification are not as pronounced as they are in the crural vessels.⁷ In our institution, plaque echogenecity is the sole indication to offer a bypass surgery for fear of distal embolization or recurrent thrombosis. On the other hand, Marks et al¹² failed in 90% of cases with GSM > 35 and 50% of cases with GSM > 25 in a study on preoperative duplex as a predictive tool for lumen re-entry during femoropopliteal angioplasty, indicating high calcification as an obstacle to successful luminal re-entry. Similarly we reported failure due to high levels of calcification and in 18% of patients who had extensive calcification on preoperative duplex, we chose bypass surgery as the primary modality.

The orthodox reporting of outcomes for CLI previously focused on graft patency, limb salvage, and survival for bypass surgery⁶ and now binary restenosis, target lesion revascularisation, limb salvage, and survival following endovascular intervention.⁹ Excellent results have been reported for these variables especially for bypass surgery, which many traditional vascular surgeons still consider the gold standard for CLI. There are consistent reports of overall patency rates ranging from 60–80% for bypass surgery, with limb salvage rates of 70–90%.⁴ In the current study, which only looked at patients with the worst TASC disease categories, our results for bypass surgery are certainly on par with previous reports with patency rates of 65.3% and amputation-free survival rates of 71.2% at 5 years.¹ Simultaneously, we showed that equally impressive, even superior, results are attainable with SIA. We achieved freedom from binary restenosis of 72.8% and amputation-free survival rates of 72.9% at 5 years without any increase in the number of repeat procedures required. Others have demonstrated impressive results with SIA, although there are few studies designed to investigate CLI, especially TASC C and D lesions, and even fewer studies with long-term follow up. Our results do concur with the declaration by Jamsen et al that SIA in patients with CLI results in gratifying limb salvage with a low number of supplementary revascularization treatments, although overall patient survival is poor.¹³

Our justification for our modus operandi of offering SIA as a first-line primary modality in the management of CLI lies in recurrent and consistent high limb salvage rates with minimal morbidity, enhanced long-term freedom from MACE, and no increase in re-intervention rates compared to traditional surgery. These endpoints are consistently achievable in management of CLI with TASC C & D lesions and similar to the findings of Kudo et al.¹⁴ Moreover our results belie the substantiation that primary SIA might influence the outcome of a secondary bypass and contradict the finding of DeRubertis et al,¹⁵ who undermined the role of SIA as a primary modality because they perceived that SIA was associated with higher re-intervention rates and eventually necessitates salvage open surgical bypass for enduring results. We found that the success of SIA is possible only with close attention to factors that directly impact on the technical outcome. Using the Cox proportional hazard ratio we found that hyperhomocystinemia was an adverse prognostic indicator for the risk of binary restenosis at 5 years for both SIA (p = 0.008) and BS (p = 0.019). Hyperhomocystinemia confers a prothrombotic effect^16,17 and promotes proliferation of smooth muscle cells¹⁸ in response to vascular injury and consequently it has been implicated in the pathogenesis of in-stent restenosis. Sultan et al¹⁹ found that hyperhomocystinemia was an independent risk factor for vascular disease and adverse prognostic factor for limb salvage and patency post-lower limb endovascular intervention. Other authors have reported this association between hyperhomocystinemia and restenosis in the peripheral arteries to such an extent that homocysteine is now being dubbed the new cholesterol of the 21st century.^20,21

The benefits of being aware of the adverse effects of homocysteine is that high serum levels can be treated with folate therapy and there are reports of impressive reductions in restenosis rate and target vessel revascularization rates with folate therapy (folic acid, vitamin B₆ and vitamin B₁₂).²²

The role of stenting in femoropopliteal occlusive disease has evolved since the initial use of stainless steel stents, which showed no benefit over angioplasty alone, forcing stenting to be relegated to salvage procedures in the face of failed angioplasty.^23,24,25 However, self-expanding stents have fashioned more favorable outcomes for SFA popliteal disease following SIA, even for TASC C & D. In our studies the number of stents used per patient or the type of stent had no influence on the long-term risk of binary restenosis, which contradicts the results of Ihnat et al²⁶ that although self-expanding stents produced acceptable outcomes for treatment of SFA disease, poorer patency rates are associated with TASC C & D lesions and poor initial runoff score. However stent occlusion and in-stent stenosis did not correlate with deterioration of their tibial artery runoff. Our favorable outcomes may be due in part to intensive follow up and aggressive re-intervention for threatened stents, but it is also as a result of a comprehensive adjuvant pharmacotherapy regime.⁸ The formation of a subintimal plane in the context of TASC C & D lesions renders an extensive area of neo-lumen that is devoid of the protective antithrombotic and anti-inflammatory effects of the endothelium. The use of antiplatelet agents and calcium channel blockers, in combination with the pleiotropic effects of statins help to compensate for the prothrombotic and proinflammatory effects of SIA and stenting. This finding is not limited to our experience, and other authors have reported on the positive effects of antiplatelets and statins in reducing the need for TLR, independently of a reduction in MACE.²⁷ This is all the more relevant due to the adverse prognostic influence of proinflammatory and prothrombotic states on the outcome from intervention found by our group and others.^28–32 We found both elevated CRP and elevated fibrinogen prognostic of reduced amputation-free survival at 5 years. 

Although we can demonstrate the technical proficiency of limb salvage surgery and now endovascular techniques, the body of evidence on patient-oriented outcomes is rather weak. This has been identified as a critical issue by the TransAtlantic Intersociety Consensus committee, who criticize the lack of quality of life instruments that have been standardized in patients requiring treatment for CLI.¹ A robust assessment of the incremental benefit in quality of life outcomes for the individual, in combination with accurate evaluation of cost-effectiveness is particularly desirable in the context of the population at risk for CLI. Experience has taught us the benefits of ample intervention in our octogenarian population.^3,33 However, we are more pragmatic and not as quick to advocate intervention in our centurion patients because the functional upshot for CLI patients undergoing EvR with SIA is not solely determined by the traditional measures of reconstruction patency and limb salvage, but by genuine inherent patient comorbidities. Our findings exemplify the reservations echoed by Taylor et al³⁴ that our current “do no harm” approach to CLI in functionally impaired, chronically ill patients must resonate with the society views that these patients are at the end of their life and longevity of sick centurions is limited. This issue will undoubtedly become more prevalent as our population greys and ages.

Previous methods for evaluating quality of life and functional status are considerably flawed. The retrospective analysis by Taylor et al³⁴ used independent living and ambulatory status as surrogate indicators of functional capacity. They looked at the 5-year outcome for 1000 patients following surgical reconstruction for CLI. Despite excellent patency (72.4%) and limb salvage rates (72.1%), 5-year survival rates were predictably low at 41.9%; 70.6% of patients were capable of independent living, while 81.3% could ambulate on their own. The only predictors of impaired functional outcome in this study were poor preoperative functional status, dementia, and amputation. Anatomic location of the lesion, type of reconstruction and comorbidities were unhelpful in predicting functional outcome. The inadequacy of traditional reporting standards to address functional outcome was similarly demonstrated by other authors who used various parameters such as wound-healing, hospital readmissions, and secondary interventions as indicators of functional outcome and quality of life.^35,36 However, all of the above indicators of function and quality of life are limited by their relatively limited scope. Although desirable, independent living and ambulation are not necessarily accurate predictors of quality-of-life. A person who can walk does not automatically have a superior quality of life and someone may achieve a better quality of life in a well-structured assisted-living environment rather than living alone in the absence of a well-developed support structure. Several studies have also used objective assessment questionnaires in an attempt to get a global assessment of function, physical capacity, pain status, and emotional well-being.^37,38 These questionnaires have notoriously high rates of non-responders, and because the sicker and more incapacitated patients are more likely not to respond, questionnaires consequently are associated with elevated false positives and plagued with inaccuracy. We used Q-TWiST, a more robust and objective assessment of ongoing quality of life, which incorporates perioperative outcomes, readmissions, non-healing, and amputation outcomes by means of individual utility assignment to these respective health-states. Using this tool we were able to demonstrate significant reductions in the adverse effects of the primary procedure (TOX, p < 0.0001) or relapses (re-interventions and readmission, REL, p < 0.0001). The accuracy of this model was confirmed by maintenance of significance over a full range of utility values between 0 and 1.

We extended the use of the Q-TWiST model further to allow for accurate assessment of cost-effectiveness and we demonstrated considerable savings for SIA, not only at the time of the primary procedure, but also when secondary procedures and long-term follow-up costs were included. Cost benefits of endovascular intervention in peripheral vascular disease have been demonstrated by previous authors. However in previous reports, the particular issues pertaining to CLI and tissue healing are seldom addressed. Previous authors have advised reserved selective stenting, and enhanced use of outpatient endovascular suites to enhance cost-effectiveness.³⁹ However if this is to be extended to CLI we cannot ignore the issues of analgesia, treatment of concomitant infection, and wound healing, which require further development to enhance efficiency and increase the potential for outpatient management.

Amidst all the debate on endovascular versus surgical revascularization and the durability thereof, we cannot forget that durability is not our ultimate goal. In a sick and greying population, quality of life takes precedence and to this end, intervention is not always best. There are patients who are best served by nonoperative management by virtue of very advanced age, severe comorbidity, or lack of anatomical suitability for vascular reconstruction. There are effective options for these patients, such as intermittent compression therapy, which can be used in combination with optimal pharmacotherapy and does not preclude the concomitant use of tissue healing therapies such as vacuum-assisted closure even on an outpatient basis.⁴⁰

In conclusion, BS is an independent risk factor for MAE. Five years freedom from MAE in SIA is enhanced by 20%. SIA augments patient-specific Q-TWiST with substantial cost reduction, expands AFS and symptom-free survival, and is minimally invasive, allowing for a high patient turnover without compromising limb salvage. Patient selection is therefore probably a good explanation for the wide variation in published results. As long as there is no randomized trial comparing SIA to surgery, we must be critical. However, with the available data currently at hand, this technique seems to be efficacious and sustainable. SIA has caused a paradigm shift and is now the gold standard in management of CLI.

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From the Western Vascular Institute, University College Hospital Galway, Galway, Ireland.
The authors report no conflicts of interest regarding the content herein.
Manuscript submitted March 23, 2011, provisional acceptance given June 23, 2011, final version accepted July 11, 2011.
Address for correspondence: Sherif Sultan, MD, Western Vascular Institute, University College Hospital Galway, Newcastle Road, Galway, Ireland, E-mail: mrsherif.sultan@gmail.com