Clinical success using patient-oriented outcome measures after lower extremity bypass and endovascular intervention for ischemic tissue loss
Article Outline
Introduction
Successful outcome after lower extremity revascularization is usually measured by physician-oriented terms such as graft patency and amputation-free survival. It has been increasingly appreciated that these criteria do not necessarily translate into success from the prospective of the patient. The purpose of this study, therefore, is to retrospectively examine success after lower extremity revascularization for tissue loss using patient-oriented measures and to include patients who underwent both open surgical bypass and endovascular therapy.
Methods
Between 1998 and 2005, 677 patients (316 endovascular and 361 open surgery) underwent revascularization for ischemic tissue loss. The method of revascularization (endovascular or open surgery) was left to the discretion of the surgeon. Revascularization was considered to be clinically successful if each of the following occurred: reconstruction patency until wound healing, limb salvage for 1 year, maintenance of ambulation for 1 year, and survival for 6 months. The influence of 20 intrinsic patient factors, including type of revascularization (open vs endo) was examined using the χ2 test. Significant factors in bivariate analysis were included in a logistic regression model to determine independent predictors and probability of failure.
Results
Overall clinical success was achieved in 277 (40.9%) patients. Success for open surgical and endovascular cohorts was 44.3% and 37.0%, respectively (P = .06). Type of intervention was not a significant factor in either bivariate or logistic regression analysis. Independent predictors of failure (odds ratio [OR]; 95% confidence interval [CI]) regardless of treatment type included impaired ambulatory status at the time of presentation (OR 3.24; CI 2.14, 4.90), diabetes (OR 1.62; CI 1.14, 2.32), endstage renal disease (ESRD) (OR 1.55; CI 1.07, 2.23), presence of gangrene (OR 2.0; CI 1.42, 2.82), and prior vascular intervention (OR 1.46; CI 1.02, 2.10). Paradoxically, hyperlipidemia (OR 0.70; CI 0.50, 0.98) was a predictor for success. Probability of failure was 35.4% (OR 1.0) if no independent predictors were present and increased with the addition of each adverse predictor. For instance, diabetic patients with impaired ambulatory status and gangrene had an 85.2% (OR 10.5) probability of failure. In the worst case scenario, a diabetic patient with ESRD, impaired ambulatory status, gangrene, and a prior vascular intervention was considered, probability of failure was a dismal 92.8% (OR 23.7).
Conclusion
Clinical success after lower extremity revascularization for ischemic tissue loss is determined by intrinsic patient factors and not by method of revascularization. These data reiterate that future investigation efforts should be focused less on the method of revascularization and more on identification of patient cohorts at risk for failure regardless of treatment.
Successful outcome after lower extremity revascularization is usually measured by physician-oriented terms such as graft patency and amputation-free survival. It has been increasingly appreciated that these criteria do not necessarily translate into success from the prospective of the patient. This is particularly true for ischemic tissue loss where research has shown that such patients often experience extended morbidity and chronic debility after revascularization.1, 2, 3 In 2006, we examined a cohort of patients with ischemic tissue loss (ulceration and gangrene), measuring success after bypass as achieving a series of practical objectives obvious to both the physician and the patient.4 In that report, success (defined as achieving graft patency to the point of wound healing, limb salvage for 1 year, maintenance of ambulation for 1 year, and survival for 6 months) was achieved in only 44.4% of patients. However, since patients with critical limb ischemia are increasingly being treated by less invasive endovascular means, the relevance of that report has been questioned. The purpose of this study, therefore, is to examine success after lower extremity revascularization for tissue loss using patient-oriented measures and to include patients who underwent both open surgical bypass and endovascular therapy.
Methods
After Institutional Review Committee approval, a retrospective study was designed to calculate the success rate after surgical bypass. Success was defined as an intervention which achieved all of the following endpoints: (1) interventional or graft patency to the point of wound healing, (2) limb salvage for 1 year, (3) maintenance of ambulatory status for 1 year, and (4) survival for 6 months.
The lower extremity peripheral arterial disease database of Greenville Hospital System University Medical Center's Vascular Teaching Service was reviewed from January 1, 1998, to December 31, 2005, for all cases of lower extremity ischemic tissue loss (Rutherford Class III) treated with surgical bypass or endovascular intervention. We identified 677 consecutive patients who underwent technically successful unilateral revascularization, whose baseline demographic characteristics are shown in Table I. Each of the 677 patients who underwent revascularization to a unilateral extremity was analyzed for successful outcome using the above definition. Of the 677 procedures, 316 were endovascular interventions and 361 were open bypasses. Patients who had a concomitant endovascular procedure at the time of their open operation were considered with the open operation cohort. When utilizing endovascular intervention as the only means of revascularization, the goal of the operator, typically, was to establish in-line flow to the ischemic foot. Therefore, multiple angioplasties were often performed. Of the 316 endovascular procedures, 227 involved angioplasties of infrainguinal arteries, 64 involved angioplasties of aortoiliac arteries, and 25 involved angioplasties of both aortoiliac and infrainguinal arteries. Of the 361 open operations, there were 98 femoral-popliteal bypasses, 137 femoral-tibial bypasses, 70 popliteal-tibial bypasses, 6 tibial-tibial bypasses, 24 aortobifemoral bypasses, 13 iliofemoral bypasses, 9 femoral-femoral bypasses, and 4 axillofemoral bypasses. Type of intervention (open bypass or endovascular intervention) was performed at the discretion of the attending physician. Typically, more severe anatomic diseases, such as Trans Atlantic Inter-Societal Consensus (TASC) classification C or D lesions, were treated with open bypass where less severe anatomic disease were treated with endovascular intervention. As well, treatment was often directed according to the Lower Extremity Grading System (LEGS) score where a LEGS score from 0-9 was treated with open bypass and a LEGS score of 10-19 was treated with endovascular intervention.5 In cases where subsequent bypass was performed for ischemic symptoms of the contralateral extremity, the initial procedure was considered the index operation and outcomes from the non-index operation were excluded from analysis. When considering the first component of our definition for success (interventional or graft patency to the point of wound healing), any endovascular intervention which resulted in an increased ankle-brachial index of at least 0.15 was considered a technical success. Conversely, an ankle-brachial index which diminished to within 0.15 of the pre-interventional ankle-brachial index associated with duplex scan or angiographic evidence of restenosis was considered a failed intervention. If the index procedure, be it open bypass or endovascular intervention, was patent at the time of wound healing, the intervention was considered a success. This included interventions or bypasses which may have undergone adjunctive procedures to maintain patency (thus the successful definition included bypasses with primary assisted patency or secondary patency). All patients have been followed using the protocols established for our lower extremity database surveillance program, as follows.
Table I. Demographic characteristics of 677 patients receiving lower extremity revascularization for critical limb ischemia with tissue loss
| Patient characteristics | Percentage (N) | ||
|---|---|---|---|
| Endo N = 316 | Open N = 361 | P value | |
| Male | 51.27 (162) | 60.39(218) | .017 |
| Smoker | 57.28(181) | 64.27(232) | .063 |
| Diabetes mellitus | 68.04(215) | 67.04(242) | .781 |
| Endstage renal disease | 41.77(132) | 25.21(91) | <.001 |
| Coronary artery disease | 65.82(208) | 58.45(211) | .049 |
| Hypertension | 82.59(261) | 82.55(298) | .987 |
| Hyperlipidemia | 38.92(123) | 35.73(129) | .392 |
| Obese (BMI >30) | 18.35(58) | 14.13(51) | .135 |
| Chronic obstructive pulmonary disease | 20.25(64) | 19.94(72) | .920 |
| Cerebral vascular accident | 20.25(64) | 19.11(69) | .710 |
| CVD | 25.32(80) | 22.44(81) | .380 |
| Dementia | 14.56(46) | 6.65(24) | <.001 |
| History of prior vascular surgery | 29.75(94) | 32.41(117) | .455 |
| Independent living | 90.19(285) | 96.95(350) | <.001 |
| Race | |||
| White | 75.00(237) | 69.81(252) | .132 |
| Other | 25.00(79) | 30.19(109) | |
| Ambulatory | |||
| Ambulatory | 64.56(204) | 81.16(293) | <.001 |
| Impaired | 35.44(112) | 18.84(68) | |
| Disease level | |||
| AIOD | 20.25(64) | 11.91(43) | .003 |
| Infrainguinal | 71.84(227) | 82.83(299) | |
| Both | 7.91(25) | 5.26(19) | |
| Presentation | |||
| Gangrene | 37.03(117) | 39.89(144) | .445 |
| Ischemic ulceration | 62.97(199) | 60.11(217) | |
| Mean (Std. Dev.) | |||
| Age (years) | 68.6(12.0) | ||
The Vascular Surgery Database was established in 1992, registering all cases performed on the vascular surgery teaching service. Since 1998, the year our endovascular program was initiated, a subset of patients with lower extremity peripheral arterial disease has been closely scrutinized and actively followed. Each lower extremity vascular procedure is entered on an Excel spreadsheet (Microsoft Corp, Redmond, Wash). Preoperative demographics are obtained at presentation and entered into the database. Functional information to include ambulatory and independent living status is also included and information is updated with each follow-up office visit. Routine follow-up for infrainguinal bypass grafts includes noninvasive duplex scan-derived graft flow velocities obtained at 1 month and every 3 months for the first 18 months and then every 6 months thereafter. Interventions for failing bypass grafts (intrinsic or juxta anastomotic stenoses with a graft flow velocity >300 cm per second and distal velocities <45 cm per second) are performed to restore normal hemodynamics. Patients receiving bypass for aortoiliac occlusive disease are followed with a patient visit and an ankle-brachial index study at 1-month and then at 6-month intervals. Patients receiving an endovascular procedure are assessed with ankle-brachial index within 1 month of intervention and followed-up with repeat ankle-brachial index every 6 months. In patients with tissue loss, office visits for wound management are scheduled as needed.
In addition to information obtained at each follow-up visit, the database is scrutinized each summer by independent research workers looking for missing data points or missing patients. Sources used to attain follow-up include the hospital computerized Lifetime Clinical Record, the computerized radiology Picture Archiving Communication System (PACS), and the online obituary services of all state-wide newspapers. Using the above, follow-up was completed on all 677 patients studied.
For the purpose of this study, the clinical course of each patient was reviewed and measured using the four defined parameters of clinical success (graft patency to the point of wound healing; limb salvage for 1 year; maintenance of ambulatory status for 1 year; and survival for 6 months). Only patients who achieved all four of the criteria were considered to have had a successful outcome. The clinical success rate was then calculated for all 677 patients as well as the 316 patients undergoing endovascular intervention and the 361 patients undergoing open bypass. Next, the influence of a series of patient factors and comorbidities on clinical success was analyzed using bivariate and multivariate logistic regression analysis. Factors analyzed included age, gender, ethnicity, history of cigarette smoking, presence of diabetes, presence of endstage renal disease, presence of coronary artery disease (moderate to high risk as scored by the Eagle criteria),6 the presence of hypertension, the presence of hyperlipidemia, obesity (body mass index [BMI] >30), the presence of chronic obstructive pulmonary disease, a history of cerebrovascular accident, a history of associated cerebrovascular disease, a history of dementia, history of prior vascular surgery, independent living status, preoperative ambulatory status, the level of atherosclerotic disease (aortoiliac vs infrainguinal), presentation (ischemic ulcer vs gangrene) and type of intervention (endovascular or open bypass). In our database, preoperative ambulatory status is characterized as ambulatory (independent ambulation out of house), ambulatory/homebound (ambulatory in home only), nonambulatory/transfer (eg, uses legs to transfer from bed to chair or from the chair to the commode), or nonambulatory/bedridden. In each case, ambulatory status is determined by physical conditions thought to be independent of their vascular disease. Thus, ambulatory status is defined as the patient's functional status immediately before the development of vascular symptoms. With this definition, ambulatory impairment is usually a function of other medical comorbidities such as arthritis, sequelae of cerebrovascular and cardiovascular disease, or advanced age. For the purpose of the study, we grouped patients classified as ambulatory/homebound or nonambulatory/transfer only together, and termed them as “impaired ambulatory status”. None of the 677 patients in the study had the preoperative classification of nonambulatory/bedridden. As well, for the purpose of this study, a change in ambulatory status was defined as a permanent postoperative change in ambulatory classification, despite full recovery from surgery (eg, ambulatory to impaired ambulatory status).
Lastly, comorbidities found to be significant in bivariate analysis were studied using logistic regression analysis to determine independent predictors of failure. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Since the type of intervention (endovascular intervention or open bypass) was of particular interest, this was included in the full logistic regression model as well. Additionally, any variables that were significant in bivariate analysis when independently examining the open and endovascular surgery subgroups were also included in the full model. After determining these independent predictors of failure, probability of failure (%) was calculated for each predictor and for combinations of predictors.
Statistical analysis
The χ2 tests were used for bivariate analyses of failure and categorical patient characteristics, while t test was used for comparing mean age of successes and failures. Logistic regression was used to model the likelihood of a failed outcome given specific patient characteristics. The ORs and 95% CIs were estimated. All variables that were significant in the bivariate analyses were included in the full model. Probability of failure (%) was determined using logistic regression. The data analysis was generated using SAS software, v 9.1.3 of the SAS System (SAS Inc, Cary, NC).
Results
Follow-up was complete for all 677 patients. Table II shows results from each of the four measures of clinical success listed separately and in combination. If the four determinants were considered separately, then success after bypass ranged from 43.6% (patency to the point of wound healing) to 84.6% (survival for 6 months). However, if all parameters were combined, clinical success was achieved in only 40.9% of patients (n = 277/677). When considering clinical success by type of treatment performed, success was achieved in 44.3% (n = 160/361) of patients undergoing open bypass and 37% (n = 117/316) of patients undergoing endovascular intervention, a difference (P = .05) almost reaching statistical significance (defined as P < .05). While the need for contralateral vascular intervention was considered a neutral occurrence in our definition of clinical success, it is noteworthy that no patient experienced clinical failure because of a mortality or permanent loss of ambulatory ability as a result of the contralateral intervention.
Table II. Independent and combined measures of success for 677 patients receiving lower extremity revascularization
| Outcome parameter | Number successful (%) | Number failed (%) |
|---|---|---|
| Intervention patency to the point of healing | 295(43.6) | 382(56.4) |
| Limb salvage for 1 year | 512(75.6) | 165(24.3) |
| Maintenance of ambulatory status for 1 year | 572(84.5) | 105(15.5) |
| Survival for 6 months | 573(84.6) | 104(15.4) |
| Clinical outcome combining all parameters | 277(40.9) | 400(59.1) |
Of the four components comprising the definition, “patency to the point of wound healing” was the most discriminatory element (43.6% overall success). Analysis of this component showed that while 494/677 (73%) interventions remained patent during the study period, only 295 foot wounds healed; an additional 12 wounds healed with a failed revascularization. Patency was similar for open surgery and endovascular intervention (273/361 [75.6%]) and (221/316 [69.9%], respectively; P = .097). However, wound healing, though not impressive for either therapy, was significantly better for open surgery (171/361 [47.4%]) when compared to endovascular intervention (124/316 [39.2%]) (P = .033).
The influence of patient comorbidities on the success rate for the entire cohort of 677 patients is shown in Table III. Statistically significant predictors of poor outcome using bivariate analysis included the presence of diabetes mellitus, the presence of endstage renal disease, the diagnosis of dementia, a history of prior vascular surgery, independent living status, impaired ambulatory status at presentation, the presence of infrainguinal disease requiring bypass (as opposed to aortoiliac occlusive disease), and the presence of gangrene. When success rates were considered separately for the 361 patients treated with open bypass and the 316 patients treated with endovascular intervention using bivariate analysis, the statistically significant predictors of poor outcome were similar to those identified for the entire cohort (Table IV). Bivariate analysis identified eight statistically significant predictors of outcome for the entire cohort (n = 677), eight statistically significant predictors of outcome for the open surgery cohort (n = 361), and five statistically significant predictors of outcome for the endovascular cohort (n = 316). The only unique predictor in the open surgery group not found in the entire cohort was hyperlipidemia. The only unique predictor in the endovascular group not found in the entire cohort was hypertension. Statistically significant independent predictors of failure, ORs, and 95% CIs were calculated using multivariate logistic regression analysis. All significant predictors in bivariate analysis (P ≤ .05) for the entire cohort, the open surgery cohort (ie, hyperlipidemia), and the endovascular cohort (ie, hypertension) were included in the full model. This included “type of treatment” (endovascular vs open surgery; P = .5) as well. Results (OR; 95% CI) showed that statistically significant patient predictors of failure after revascularization included impaired ambulatory status at presentation (OR 3.24; CI 2.14, 4.90), the presence of diabetes (OR 1.62; CI 1.14, 2.32), the presence of endstage renal disease (OR 1.55; CI 1.07, 2.23), the presence of gangrene (OR 2.0; CI 1.42, 2.82), and a history of prior vascular intervention (OR 1.46; CI 1.02, 2.10). The presence of hyperlipidemia paradoxically was an independent predictor of success (OR 0.70; CI 0.50, 0.98). Of note, “type of treatment” when entered into the logistic regression model and refined by backward selection (selection criteria = 0.05), fell quickly out of the equation, emphasizing that method of revascularization did not predict successful outcome.
Table III. Bivariate analysis of patient factors and comorbidities of failure after revascularization using a patient-oriented definition of success
| Characteristic | Percentage with failure (n) | P value |
|---|---|---|
| Type | ||
| Open | 55.68(201) | .05 |
| Endo | 62.97(199) | |
| Gender | ||
| Female | 57.09(169) | .33 |
| Male | 60.79(231) | |
| Race | ||
| White | 57.67(282) | .23 |
| Other | 62.77(118) | |
| Smoker | ||
| Yes | 58.60(242) | .75 |
| No | 59.85(158) | |
| Diabetes mellitus | ||
| Yes | 63.68(291) | <.01⁎ |
| No | 49.55(109) | |
| Endstage renal disease | ||
| Yes | 70.40(157) | <.01⁎ |
| No | 53.42(242) | |
| Coronary artery disease | ||
| Yes | 61.34(257) | .13 |
| No | 55.43(143) | |
| Hypertension | ||
| Yes | 60.64(339) | .07 |
| No | 51.69(61) | |
| Hyperlipidemia | ||
| Yes | 55.16(139) | .11 |
| No | 61.41(261) | |
| Obese(BMI >30) | ||
| Yes | 54.13(59) | .25 |
| No | 60.04(341) | |
| Chronic obstructive pulmonary disease | ||
| Yes | 63.24(86) | .27 |
| No | 58.04(314) | |
| Cerebral vascular accident | ||
| Yes | 57.14(76) | .61 |
| No | 59.56(324) | |
| Cardiovascular disease | ||
| Yes | 59.01(95) | .98 |
| No | 59.11(305) | |
| Dementia | ||
| Yes | 75.71(53) | <.01⁎ |
| No | 57.17(347) | |
| History of prior vascular surgery | ||
| Yes | 66.35(140) | .01⁎ |
| No | 55.79(260) | |
| Independent living status | ||
| Independent | 57.95(368) | .02⁎ |
| Non-Independent | 76.19(32) | |
| Ambulatory | ||
| Ambulatory | 51.91(258) | <.01⁎ |
| Impaired ambulation | 78.89(142) | |
| Disease level | ||
| AIOD | 44.86(48) | <.01⁎ |
| Infrainguinal | 61.98(326) | |
| Both | 59.09(26) | |
| Presentation | ||
| Gangrene | 70.11(183) | <.01⁎ |
| Ischemic ulceration | 52.16(217) | |
| Age | ||
| Mean age for successes | 68.8(Std.Dev.:12.2) | .67 |
| Mean age for non-successes | 68.4(Std.Dev.:11.8) |
⁎denotes statistically significant at alpha = 0.05. |
Table IV. A comparison of bivariate results by procedure type (bivariate analysis of patient characteristics and success/failure outcome using χ2 test)
| Characteristic | P value | ||
|---|---|---|---|
| Overall N = 677 | Endo N = 316 | Open N = 361 | |
| Type | .05 | — | — |
| Gender | .33 | .06 | .88 |
| Race | .23 | .16 | .59 |
| Smoker | .75 | .48 | .36 |
| Diabetes mellitus | <.01⁎ | .01⁎ | .02⁎ |
| Endstage renal disease | <.01⁎ | <.01⁎ | .04⁎ |
| Coronary artery disease | .13 | .14 | .59 |
| Hypertension | .07 | .04⁎ | .56 |
| Hyperlipidemia | .11 | .90 | .02⁎ |
| Obese (BMI >30) | .25 | .87 | .10 |
| Chronic obstructive pulmonary disease | .27 | .84 | .19 |
| Cerebral vascular accident | .61 | .21 | .67 |
| Cardiovascular disease | .98 | .37 | .46 |
| Dementia | <.01⁎ | .18 | <.01⁎ |
| History of prior vascular surgery | .01⁎ | .08 | .05⁎ |
| Independent living status | .02⁎ | .08 | .25 |
| Ambulatory | <.01⁎ | <.01⁎ | <.01⁎ |
| Disease level | <.01⁎ | .11 | <.01⁎ |
| Presentation | <.01⁎ | .01⁎ | <.01⁎ |
| Age | .67 | .50 | .65 |
⁎Denotes statistically significant at alpha = .05. |
Finally, the probability of failure for each independent predictor, alone and in combination, is shown in Table V. If no independent predictors of failure were present at the time of revascularization, the probability of failure was 35.4% (OR 1.0). While the probability of failure increased significantly when associated with each independent predictor; the presence of multiple predictors had particularly poor prognoses. For example, if a patient presented with all six independent predictors, the probability of failure was 90.1%. Patients presenting with every independent predictor of adverse outcome (impaired ambulation at presentation, the presence of diabetes, the presence of endstage renal disease, gangrene as opposed to ischemic ulceration, and a prior vascular intervention) experienced only a 7.2% chance of success.
Table V. The probability of failure for each independent predictor of failure alone and in combination
| Patient characteristic(s) present | Probability of failure (%) | Odds ratio of given profile compared to a “healthy” person* |
|---|---|---|
| (#1) Impaired ambulation at baseline | 64.0% | 3.2 |
| (#2) Diabetes | 47.1% | 1.6 |
| (#3) ESRD | 45.9% | 1.5 |
| (#4) Hyperlipidemia | 27.7% | 0.7 |
| (#5) Gangrene | 52.3% | 2.0 |
| (#6) Prior vascular intervention | 44.4% | 1.5 |
| Predictive variables #1-6 | 90.1% | 16.5 |
| Predictive variables #1,2,3,5,6 | 92.8% | 23.7 |
| Predictive variables #1,2 | 74.2% | 5.3 |
| Predictive variables #1,2,3 | 81.7% | 8.1 |
| Predictive variables #5,6 | 61.5% | 2.9 |
| Predictive variables #1,2,5 | 85.2% | 10.5 |
| Predictive variables #2,3 | 57.9% | 2.5 |
| Baseline/“healthy person” | 35.4% | 1.0 |
Discussion
Since its original description, operative bypass for chronic lower extremity ischemia has been evaluated by measuring graft patency and limb salvage. It is intuitive to believe that accomplishing these objectives should translate into a successful outcome. However, in the late 1990s, a series of reports emerged suggesting that graft patency and limb salvage only tell part of the story. Specifically, reports from the University of Oregon showed that patients undergoing bypass for critical limb ischemia had a frequent ongoing need for care, with prolonged periods of wound healing and subsequent operations to maintain graft patency.1, 2 In their large registry of patients, only 14% had an uncomplicated operation, relief of symptoms, complete wound healing, no need for repeat operation, and maintenance of functional status. For the remaining 86% of patients, a major portion of their remaining lives were spent with ongoing treatment for critical limb ischemia. These papers had a profound impact on the vascular community, causing many to question our current approach to limb salvage. Acknowledging that much of the early literature devoted to critical limb ischemia measured success after revascularization using physician-oriented endpoints and not patient-oriented endpoints, the leadership in vascular surgery recently published a directive in a supplement of the Journal of Vascular Surgery establishing the development of patient-oriented endpoints as a major future research objective.7 In response, our group published a study examining 331 patients who underwent lower extremity bypass for tissue loss where we measured success as achieving bypass patency until wound healing, limb salvage for 1 year, maintenance of ambulatory status for 1 year, and survival for 6 months. In that report, clinical success was achieved in only 44% of patients. Independent predictors of failure included impaired ambulatory status at presentation, endstage renal disease, the need for an infrainguinal bypass, and the presence of gangrene (as opposed to ischemic ulceration).4
Since publishing that report, we have received much constructive and critical feedback. Criticism has been levied in two areas; the arbitrary nature of our definition for success, and the exclusion of patients undergoing endovascular intervention for ischemic tissue loss. Admittedly, our definition of success is entirely arbitrary. In establishing the definition, we wanted to take a perspective from the patient's point of view and, thus, constructed a common sense description of success that would be obvious to everyone. However, we wanted the definition to be fair and within a reasonable realm of medical attainability. The first component, patency to the point of healing, intuitively meets these criteria. Our intent with this component was to measure treatment effectiveness (successful relief of ischemia such that healing occurred). If an intervention were to thrombose and patency not re-established prior to healing, or if a wound failed to heal despite a patent intervention, it would be obvious that the intervention was a failure. Conversely, if an intervention were to fail but a wound healed anyway, some might consider the original intervention as unnecessary. The second and third components, limb salvage and maintenance of ambulatory status for 1 year, though temporally arbitrary, met criteria and seemed reasonable. The final component, survival for 6 months, has been particularly scrutinized. In establishing this component, our intention was to utilize mortality as a measure of perioperative patient safety, not necessarily a measure of patient longevity. Clearly, a successful intervention should result in a low mortality. Any mortality after 6 months, we reasoned, was most likely not related to the intervention. However, long-term survival for patients with ischemic tissue loss is poor. Mortality for patients with critical limb ischemia is roughly 6% per year.8 In a report from our institution looking exclusively at patients with tissue loss, 5-year survival was only 29%.9 We, therefore, felt that any definition of success tied in any way to long-term survival may not be readily achievable and, thus, is probably unfair. Therefore, we chose survival for 6 months as the final component of our definition.
We have come to believe that the criticism attributed to our exclusion of patients undergoing endovascular intervention for ischemic tissue loss is valid and, consequently, became the motivation for this study. Endovascular therapy has increasingly become initial therapy for many patients with critical limb ischemia. Examination of our current database demonstrates this. Nearly half of the patients with ischemic tissue loss were treated initially with endovascular intervention. Endovascular intervention carries a lower morbidity and mortality and, while it is less durable than open bypass, theoretically results in situational perfusion capable of healing ischemic ulcers. Clearly, including endovascular intervention cases into this current analysis appears to be a reasonable proposition and, therefore, more accurately depicts the current practice of most vascular surgeons. In doing so, this study contains a more robust number of patients than our original report and allows comparison between patients undergoing endovascular intervention and open bypass. We found that when combining open bypass with endovascular intervention, overall success as defined was 40.9%. Though postulated by some, patients treated with less invasive endovascular therapy did not fare better than patients treated with open surgery. To the contrary, the open surgery cohort experienced overall success in 44% of patients compared to 37% of endovascular patients, a difference approaching statistical significance (P = .05). Clearly, the retrospective nature of this study with its acknowledged treatment bias precludes a head-on-head comparison of success rate for open and endovascular surgery in a general sense. All we can conclude is that patients that we chose to treat with open surgery (be it on the basis of the TASC classification or the LEGS score) did as well, or perhaps a little better, than patients we chose to treat with endovascular therapy.
When considering our definition for success, outcome was most prominently dictated by the percentage of patients unable to achieve interventional patency until the point of wound healing. Of patency and wound healing, wound healing was the most discriminatory component of success, occurring in only 39% of patients after endovascular intervention. Independent predictors of failure were similar to our first report and were similar regardless of which type of initial therapy (open bypass or endovascular therapy) was employed. Independent predictors of failure included impaired ambulation at presentation, endstage renal disease, prior vascular surgery, the presence of gangrene as compared to ischemic ulceration, and diabetes. If no independent predictors of failure were present, the probability of success after intervention or bypass was nearly 65%, and if all adverse predictors of failure were present, the probability of success after intervention or bypass was only 7%. At first glance, a success rate of only 65% in the absence of independent predictors of failure seems disappointing. However, given that these patients face certain major limb amputation without revascularization, a certain degree of “failure” may be clinically acceptable in order to attempt limb salvage. We believe these results can be more appropriately used as a clinical tool for discussion with families and patients at the bedside on the opposite end of the clinical spectrum; when various independent predictors of failure are present and the clinical course favors palliative primary amputation. Given that revascularization is expensive, potentially morbid, and labor-intensive for all involved, our model assigns numerical percentages of success to various clinical situations, especially situations where outcomes appear subjectively futile.
The study has all the shortcomings of any retrospective study. Treatment was not standardized. Results are from a single center. The definition of success has not been derived from consensus. Our study included only patients felt worthy of revascularization. It excluded patients where primary amputation was felt to be the best initial course. Thus, our success rate of 40.9% represents a sobering “best case scenario.” While the results of the study help define success and failure for patients with ischemic tissue loss when no predictors or multiple predictors are present, they may create conflict when only one or two are identified. For example, when patients present with gangrene and a prior vascular intervention as the only two predictors, the probability of failure is approximately 60%. Conversely, the probability of success is nearly 40%. While these odds for success may not be particularly encouraging, they are not exactly futile either. Thus, in this instance, our model is not very helpful in directing therapy or advising families as to the best medical course based on odds of success. Clearly, more work is needed to better understand which patients achieve benefit after revascularization and which do not. To this regard, our study simply scratches the surface.
An additional finding in both this and our former study is the seemingly protective effect of hyperlipidemia (OR 0.70). The reason for this is unknown. For the purposes of this study, a patient was designated as having hyperlipidemia if an International Classification of Disease (ICD)-9 diagnosis code for hyperlipidemia was assigned to the patient's clinical record. Lab work indicative of hyperlipidemia suggests that these patients have undergone some type of cardiovascular screening and, by conjecture, are probably more conscientious about their own healthcare. Most of these patients were on statin therapy, providing further evidence that cardiovascular disease management was ongoing. Thus, the apparent protective effect of hyperlipidemia may be a function of better access to routine health maintenance or may represent a protective affect afforded by statin therapy. Further investigation is needed. Lastly, our study exposes two clinical problem areas significantly impacting success after lower extremity revascularization. As with our previous studies, patients who present with impaired ambulatory status and lower extremity ischemic tissue loss perform particularly poorly.4, 10 Further prospective study examining the appropriate care of functionally impaired patients is needed to help better direct appropriate therapy. It appears in some situations that palliative care without revascularization is warranted. Also, this study found that the healing of foot wounds was of particular concern. Healing occurred in roughly half the patients undergoing open bypass and in just over one third of patients undergoing endovascular intervention, a difference that was statistically significant. Investigation correlating the extent of foot wound involvement and expected outcomes is needed. Evidence from this study suggests that there may be limbs with foot wounds traditionally considered to be salvageable that, indeed, may not be salvageable, especially if endovascular intervention is the revascularization method utilized.
In summary, we believe this study supports the following observations. First, success from the patient's perspective is clearly different than success from the surgeon's. Future treatment options probably need to consider both. Using our patient-oriented definition, successful outcome after revascularization for tissue loss was a modest 40.9%. Next, our study shows that patients selected for open bypass do as well or perhaps a little better than patients selected for endovascular intervention. While the retrospective nature of this study with its inherent treatment selection bias precludes head-on-head comparison, it is reasonable to deduce that open surgery and endovascular therapy are complementary, not competitive techniques capable of achieving similar success rates when employed in appropriate situations. There are clinical scenarios where neither technique is appropriate and where palliation without revascularization is indicated. That would include primary amputation. Lastly, future research should be geared less toward developing new revascularization strategies that compare endovascular intervention to open bypass and more toward defining goals of treatment after revascularization. Success or failure in many cases appears to depend on the patient's overall physical and functional condition at presentation, to include the extent of foot wound involvement, and not on the vascular status of the affected limb. Indeed, our data would suggest that ischemic tissue loss, especially gangrene, is a precursor to overall patient demise in many cases. As our failing healthcare system endures increasing financial scrutiny, identification of patient cohorts incapable of achieving benefit from revascularization is desperately needed. Studies identifying such cohorts will be invaluable and will allow us to appropriately allocate our diminishing resources to achieve the greater good.
Author contributions
References
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Competition of interest: none.
PII: S0741-5214(09)00683-1
doi:10.1016/j.jvs.2009.03.030
© 2009 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
