From the Society for Clinical Vascular Surgery
Objective measurement of lower extremity function and quality of life after surgical revascularization for critical lower extremity ischemia Gregory J. Landry, MD, Nick O. Esmonde, BS, Jason R. Lewis, BS, Amir F. Azarbal, MD, Timothy K. Liem, MD, Erica L. Mitchell, MD, and Gregory L. Moneta, MD, Portland, Ore Background: Outcomes of revascularization for critical limb ischemia (CLI) have historically been patency, limb salvage, and survival. Functional status and quality of life have not been well described. This study used functional and quality of life assessments to measure patient-centered outcomes after revascularization for CLI. Methods: The study observed 18 patients (age, 65 6 11 years) prospectively before and after lower extremity bypass for CLI. Patients completed the Short Physical Performance Battery, which measures walking speed, leg strength, and balance, as well as performed a 6-minute walk, and calorie expenditure was measured by an accelerometer. Isometric muscle strength was assessed with the Muscle Function Evaluation chair (Metitur, Helsinki, Finland). Quality of life instruments included the 36-Item Short Form Health Survey and the Vascular Quality of Life questionnaire. Patients’ preoperative status was compared with 4-month postoperative status. Results: Muscle Function Evaluation chair measurements of ipsilateral leg strength demonstrated a significant increase in knee flexion from 64 6 62 N to 135 6 133 N (P [ .038) and nearly significant increase in knee extension from 120 6 110 N to 186 6 85 N (P [ .062) and ankle plantar flexion from 178 6 126 N to 267 6 252 N (P [ .078). In the contralateral leg, knee flexion increased from 71 6 96 N to 149 6 162 N (P [ .028) and knee extension from 162 6 112 N to 239 6 158 N (P [ .036). Absolute improvements were noted in 6-minute walk distance, daily calorie expenditure, and individual domains and overall Short Physical Performance Battery scores, and upper extremity strength decreased, although none were significant. The Vascular Quality of Life questionnaire captured significant improvement in all individual domains and overall score (P < .015). Significant improvement was noted only for bodily pain (P [ .011) on the 36-Item Short Form Health Survey. Conclusions: Despite lack of statistical improvement in most functional test results, revascularization for CLI results in improved patient-perceived leg function. Significant improvements in isometric muscle strength may explain the measured improvement in quality of life after revascularization for CLI. (J Vasc Surg 2014;-:1-7.)
Peripheral arterial disease (PAD) has become increasingly prevalent in this country as the population ages and the accumulation of risk factors, such as diabetes and smoking, is manifested. A fraction of patients with PAD will progress to critical limb ischemia (CLI) and will often require an intervention to salvage the limb. The success of an intervention has historically been oriented toward assessment of the results of the operation (ie, procedural patency and limb salvage), without considering how the operation affects patients in their daily lives. Subsequent studies have investigated the effects of surgery on self-
From the Division of Vascular Surgery, Knight Cardiovascular Institute, Oregon Health & Science University. Dr Landry is sponsored by NIH/NHLBI K23 HL80232-01. Author conflict of interest: none. Presented at the Thirty-ninth Annual Symposium of the Society for Clinical Vascular Surgery, Orlando, Fla, March 16-19, 2011. Reprint requests: Gregory J. Landry, MD, Associate Professor of Surgery, Division of Vascular Surgery, Knight Cardiovascular Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, OP11, Portland, OR 97239-3098 (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 0741-5214/$36.00 Copyright Ó 2014 by the Society for Vascular Surgery. http://dx.doi.org/10.1016/j.jvs.2014.01.067
reported ambulatory and living status,1,2 which, although important end points, still do not completely address patients’ physical functioning and quality of life. Treatment of peripheral vascular disease carries a significant burden for the patient and health care system alike. The paucity of literature on functional outcomes for this group led the TransAtlantic Inter-Society Consensus to state that “specific instruments capable of detecting improvement in functional status in this [CLI] population must be developed.”3 At present, there is no consensus on the appropriate tools for assessing functional and quality of life outcomes for patients who undergo a limb salvage procedure for CLI. A previous review discussed how quality of life questionnaires and functional measurements that had been validated for PAD could be adapted for patients with CLI for assessment of changes occurring during the preoperative and postoperative interval.4 These included previously validated questionnaires (36-Item Short Form Health Survey [SF-36], Vascular Quality of Life [VascuQol], and Geriatric Depression Scale) and a battery of physical tests including timed 6-minute walk, summary performance test (chair raises, balance, and 4-meter walk), daily calorie expenditure, and upper and lower extremity isometric muscle strength measured by the Muscle Function Evaluation chair (Metitur, Helsinki, Finland). This paper describes 1
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our experience with a mix of self-reported and objective assessment tools in a cohort of patients enrolled in a longitudinal study for outcomes after surgical intervention for CLI. METHODS The study was approved by the Institutional Review Board at the Oregon Health & Science University. Patients were recruited from the vascular surgery clinic at the Oregon Health & Science University. Study entry was offered to all patients undergoing surgical bypass for CLI from January 2007 to January 2009. Patients who were nonambulatory before the onset of CLI were excluded. All patients underwent standard vascular bypasses with autogenous conduit. Functional and quality of life assessments were performed preoperatively and at approximately 4 months postoperatively, depending on patients’ ability to return to the investigation site. A series of functional assessments were performed by tests previously validated in the population of patients with PAD, although not specifically for patients with CLI. Walking distance. The timed 6-minute walk has been validated as a means to evaluate leg function and exercise capacity in the elderly and PAD populations.5,6 The test is performed in a 100-foot-long flat hallway. Patients are instructed to walk back and forth as far as they can in 6 minutes. Trained personnel walk directly behind the subjects and give standardized instructions of encouragement at set intervals. Subjects determine their own pace and stop and rest, if needed. The total distance covered is recorded in linear meters. Because subjects are allowed to walk at their own pace, results of a 6-minute walk are a more accurate reflection of walking abilities, and the test is less anxiety-provoking than treadmill walking.7 Summary performance score. The summary performance score is derived from three tests: a timed 4-meter walk, the Tinetti balance test, and a timed test of muscle power in which patients stand and sit repetitively five times. These tests have been validated in a number of populations, such as stroke and geriatric patients.8,9 The timed 4-meter walk consists of two separate trials in which the patient walks in a straight line at a brisk pace for 4 meters. The faster of the two trials is recorded. The Tinetti balance equation is a well-established assessment of balance in predicting mobility in the elderly as well as in functionally impaired patients.10 Patients stand with their feet in three separate positions: side by side, in semi-tandem, and in tandem. Scores are assigned on the basis of the number of seconds that patients can hold each position, from 0 to 10 seconds. The sit-stand test is a validated test for muscle strength and function in the elderly and is predictive of need for nursing home care.8,9 Patients begin seated and are timed while they perform five repetitions of standing and sitting down. For each task, a score (1-4, with 4 being the highest) is assigned, and the cumulative score is tabulated according to an established scoring rubric. Physical activity. The Caltrac vertical accelerometer is a validated measure of physical activity and is used to
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estimate daily activity level. Patients wore the accelerometer for 5 days, and their daily activity was calculated as a total calorie expenditure and averaged to estimate a daily expenditure. This value approximates patient function outside of the clinic, in the setting of daily life and in the community.11-13 Isometric muscle strength. The Muscle Function Evaluation chair was designed for use in the setting of physical rehabilitation and fitness training. Transducers measure isometric strength in newtons in multiple muscle groups Patients were seated upright in the chair with one extremity strapped into the chair at a time. Adjustable seat back and arm and leg restraints allowed the chair to be fitted individually, such that muscle function could be evaluated in the most comfortable position. There are four force transducers located on the chair that measure strength at the elbow, knee, and talocrural joints as well as hand grip strength with isometric muscle contractions. Patients had 10 seconds to generate their maximum force possible, with 10-second rest periods in between. The largest value during those 10 seconds was recorded as a peak force in newtons. Upper extremity function was evaluated in addition to lower extremity function as a surrogate evaluation of overall postoperative deconditioning. Quality of life questionnaires. A number of selfadministered questionnaires are available to assess generalized and disease-specific quality of life. A combination of the two types of questionnaires is often employed to capture quality of life impairment due to a specific disease process vs overall quality of life. The SF-36 is widely used as a generalized quality of life assessment and has been thoroughly validated for use in patients with PAD and to a lesser extent in groups of patients with CLI. The SF-36 considers eight categories of health: physical function, role limitation due to physical problems, bodily pain, general health perception, social function, emotional wellbeing, and role limitation due to emotional well-being. The VascuQoL questionnaire was included to capture disease-specific health parameters. The VascuQoL asks 25 questions falling into five broad categories: pain, activity, emotion, symptoms, and social. Each category is scored from 1 to 7 points, with 7 being the highest, and the total is averaged for the five categories to give a summary score.14 Finally, the Geriatric Depression Scale was used in this setting on the basis of association between depressive symptoms and decline in function.15 Scores range from 1 to 15, based on the number of statements about personal health with which the patient agrees. A score above 5 is generally considered to indicate depressive symptoms. Study participation was offered to all eligible patients undergoing surgical revascularization for CLI. Exclusion criteria included nonambulatory status predating the onset of CLI and non-English speakers. Preoperative and postoperative data were compared by a paired t-test for continuous, normally distributed data and the Mann-Whitney U test for ordinal data. Statistical significance was determined at the P < .05 level.
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Table I. Demographic data of the study cohort of 18 patients and 42 nonparticipants Factor Gender, % male Mean age at surgery 6 SD, years Indication Rest pain Ulcer or gangrene Diabetes Hypertension Coronary artery disease Smoking history Hypercholesterolemia Renal insufficiency (Cr > 1.5) Dialysis dependence COPD Previous ipsilateral bypass Type of bypass Femoral-popliteal Femoral-tibial Popliteal-pedal
Study patients (n ¼ 18)
Nonparticipants (n ¼ 42)
Significance
67% 65 6 11
71% 66 6 14
NS NS NS
33% 67% 67% 72% 44% 72% 78% 11% 6% 17% 39%
45% 55% 48% 83% 48% 62% 52% 17% 7% 14% 55%
39% 50% 11%
29% 64% 7%
NS NS NS NS NS NS NS NS NS NS
COPD, Chronic obstructive pulmonary disease; Cr, creatinine; NS, not significant; SD, standard deviation.
RESULTS During the study period, 18 subjects were enrolled and completed both preoperative and postoperative assessments. Six patients had rest pain, whereas 12 had ulcers or gangrene. All underwent vein bypass with autologous conduit (7 femoralebelow-knee popliteal, 9 femoraltibial, 2 popliteal-pedal). Five patients underwent digital amputations during the follow-up period, all of which healed, with no major amputations. The mean length of follow-up at the second evaluation was 121 6 57 days. During the same period, 60 bypasses were performed in eligible patients. Six patients enrolled and completed the preoperative assessment but refused the postoperative assessment; 36 declined participation. Incomplete participants and nonparticipants cited travel distance and time commitment as reasons for refusal. There were no demographic differences between participants and nonparticipants (Table I). There was a significant increase in ankle-brachial index (ABI) of the treated extremity after surgery (0.46 6 0.17 preoperatively, 0.86 6 0.21 postoperatively; P < .001). The contralateral ABI was unchanged after surgery (0.70 6 0.22 preoperatively, 0.76 6 0.16 postoperatively). All grafts remained patent and no subjects died during the study period. The results of the functional studies are presented in Table II. There was numerical improvement in all of the parameters tested (daily calorie expenditure, 6-minute walking distance, 4-meter walking score, Tinetti standing balance score, repeated chair rises, and overall summary performance score); however, none reached statistical significance. In contrast, significant improvement was noted in multiple measurements of isometric muscle strength in both the surgical and contralateral extremities (Tables III and IV). In the ipsilateral leg, knee flexion improved significantly from 64 6 62 N preoperatively to 135 6 133 N
Table II. Functional measurements before and after lower extremity bypass for CLI Assessment Daily physical activity, calories Six-minute walk distance, meters Four-meter walk scorea Standing balancea Chair risesa Overall SPPB scorea
Preoperative
Postoperative
1773 6 1786 2064 6 1201 97 6 88 2.43 2.36 1.47 6.36
6 6 6 6
1.4 1.8 1.4 4
P value .313
128 6 75
.216
6 6 6 6
.849 .510 .417 .849
2.50 2.86 2.00 7.21
1.5 1.5 1.7 4
CLI, Critical limb ischemia; SPPB, Short Physical Performance Battery. a Scored 0 to 4. Overall score, 0 to 12: 0, worst; 12, best (reported as mean 6 standard deviation). Each measurement scored is based on established quartiles for the elderly population.
Table III. Lower extremity isometric muscle strength in the treated extremity Ipsilateral measurement
Preoperative
Ankle dorsiflexion Ankle plantar flexion Knee flexion Knee extension
124 178 64 120
6 6 6 6
87 126 62 110
Postoperative
P value
6 6 6 6
.826 .078 .038 .062
130 267 135 186
98 252 133 85
Reported in newtons (mean 6 standard deviation).
postoperatively (P ¼ .038). Strong trends toward improvement were also noted in ankle plantar flexion (178 6 126 N preoperatively vs 267 6 252 N postoperatively; P ¼ .078) and knee extension (120 6 110 N vs 186 6 85 N; P ¼ .062). Significant improvements were also noted in the contralateral limb in knee flexion (71 6 96 N preoperatively vs 149 6 162 N postoperatively; P ¼ .028) and knee extension (162 6 112 N preoperatively vs 239 6 158 N postoperatively; P ¼ .036). No significant changes in upper extremity function were noted (Table V).
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Table IV. Lower extremity isometric muscle strength in the contralateral extremity
Table VI. Quality of life before and after surgery (generalized, not disease specific)
Contralateral measurement Preoperative Postoperative P value Ankle dorsiflexion Ankle plantar flexion Knee flexion Knee extension
163 252 71 162
6 6 6 6
109 182 96 112
150 292 149 239
6 6 6 6
SF-36 93 252 162 158
.624 .368 .028 .036
Reported in newtons (mean 6 standard deviation).
Table V. Upper extremity isometric muscle strength Upper extremity measurement
Preoperative
Right elbow flexion Left elbow flexion Right elbow extension Left elbow extension Right hand grip Left hand grip
160 114 118 108 266 261
6 6 6 6 6 6
97 74 63 77 140 149
Postoperative
P value
6 6 6 6 6 6
.322 .272 .662 .981 .199 .253
143 137 109 107 236 220
64 74 60 61 128 138
Reported in newtons (mean 6 standard deviation).
In the generalized quality of life questionnaire (SF-36), a significant improvement was seen only in the domain of bodily pain (preoperative score, 25 6 19; postoperative score, 45 6 21; P ¼ .001), with a strong trend toward improvement in role limitations due to physical health (preoperative score, 4 6 13; postoperative score, 29 6 42; P ¼ .067). No differences were noted in the domains of physical functioning, general health, vitality, social functioning, role limitations due to emotional problems, or mental health (Table VI). In the disease-specific quality of life questionnaire (VascuQol), significant improvements were noted in all domains and in the total score (Table VII). There was no significant change in the Geriatric Depression Scale score (preoperative score, 4.1 6 3.8; postoperative score, 4.9 6 2.9; P ¼ .394). Four subjects (22.2%) had clinically significant depression scores ($6), with no significant change after revascularization. DISCUSSION Assessment of functional outcomes of surgical revascularization for CLI has undergone a significant evolution in the past two decades. For many years, the outcomes of surgical revascularization for CLI were reported as graft patency, limb salvage, and survival. These remain important parameters as good leg function is dependent on optimal perfusion. However, graft patency tends to be a “lesion-oriented” outcome measure and may not reflect how well a patient is performing functionally. In the 1990s, the emphasis of outcomes reporting shifted to more “patient-oriented” outcomes.1,2 Ambulatory status and living status (ie, independent vs nonindependent living) were reported, and self-reported quality of life assessments became standard reporting measures. Numerous studies
Physical functioning Role limitations due to physical health Bodily pain General health Vitality Social functioning Role limitations due to emotional problems Mental health
Preoperative scorea
Postoperative scorea
P value
30 6 23 4 6 13
45 6 30 29 6 42
.172 .067
6 6 6 6 6
21 14 19 27 43
.001 .36 .532 .151 .675
76 6 14
.246
25 49 42 47 57
6 6 6 6 6
19 21 19 28 50
69 6 19
45 54 46 58 65
SF-36, 36-Item Short Form Health Survey. a Scored 0 to 100 (reported mean 6 standard deviation): 0, worst; 100, best.
Table VII. Quality of life before and after surgery (disease specific) VascuQol Activity Symptoms Pain Emotional Social Total score
Preoperative scorea 2.32 3.35 2.53 3.60 2.84 2.93
6 6 6 6 6 6
0.95 1.38 1.06 1.33 1.50 0.93
Postoperative scorea
P value
6 6 6 6 6 6
.001 .001 .002 .014 .001 .001
4.04 5.22 4.45 5.06 5.09 4.66
1.44 1.14 1.83 1.37 1.45 1.28
VascuQol, Vascular Quality of Life questionnaire. a Scored 1 to 7 (reported mean 6 standard deviation): 1, worst; 7, best.
have subsequently confirmed functional improvements in the majority of patients on the basis of these measures.16-19 However, graft patency does not always translate to good function. A recent study from the Vascular Surgery Group of New England demonstrated that 10% of patients experienced clinical failure at 1 year after bypass, defined as amputation or worsening ischemia, despite having a patent graft.20 Taylor21 defined clinical success as graft patency to the point of wound healing, limb salvage, and ambulation for 1 year after bypass and survival for 6 months. Only 44% of 331 consecutive bypass patients were able to achieve clinical success. The use of ambulatory status and living status as outcome measures makes assumptions that may not be true for all patients. Whereas independent ambulation is a desirable outcome to preserve, as a binary variable it leaves many unanswered questions about the duration or quality of ambulation, and it does not assess how patients perform in their activities of daily living. Kumar22 demonstrated that although revascularization allowed preservation of ambulatory function, only 53% of working patients were able to return to their original work. Likewise, whereas independent living is preferable for most people, a high level of functionality is certainly possible in an assisted living environment. Self-reported quality of life questionnaires also are inherently flawed in that they rely on patients’ perceptions and
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recollections and may not accurately reflect actual function. As stated by the Nobel Prize-winning psychologist Daniel Kahneman, when one is asked about quality of life, “A few ideas that are relevant to the question will occur to you; many others will not . the score that you quickly assign to your life is determined by a small sample of highly available ideas, not by a careful weighting of the domains of your life.”23 The lack of a validated functional assessment tool to evaluate interventions for CLI was cited in the TransAtlantic Inter-Society Consensus I document as a critical issue for further research. In this study, we used a battery of functional assessments that have previously been used extensively in the assessment of geriatric patients, although not specifically to assess the results of intervention. Quality of life improvements after successful revascularization were noted in this patient population. All domains of the VascuQol demonstrated significant improvements at 4 months, as did the aggregate score. In the SF-36 analysis, only the pain domain showed significant improvement. These findings are in line with numerous previous studies that have shown similar improvements in selfreported quality of life with use of a variety of general and disease-specific quality of life measures, the largest of which, the Prevention of Recurrent Venous Thromboembolism (PREVENT) III trial, examined more than 1400 subjects.24 In contrast, Cieri et al,25 using the Katz index, noted a significant decline in the ability to perform activities of daily living after both surgical and endovascular revascularization, despite successful limb preservation and improvements in pain relief and tissue healing. McDermott et al15 noted a high prevalence of depressive symptoms in patients with symptomatic PAD, with 21.7% of patients exhibiting significant depressive symptoms and a greater number of depressive symptoms associated with greater impairment of lower extremity function. In our study, a similar percentage of patients (22.2%) exhibited significant depressive symptoms but with no significant change after successful revascularization. Of the objective functional measures performed, the results of evaluation with the Muscle Function Evaluation chair correlated best with the self-reported quality of life findings. Isometric muscle strength has been found to be diminished in the distal extremities in patients with PAD and is correlated with diminished ABI.26 Subjects with PAD and diminished baseline muscle strength have been shown to have increased long-term functional decline and mortality.27,28 The Muscle Function Evaluation chair measures isometric muscle strength in multiple groups. How revascularization improves muscle strength is not clear. Whether actual muscle mass improves is not known. It is perhaps more likely that improvement in ischemic pain allows better performance. Whereas there was a trend toward improvement in all of the functional measures, only in the Muscle Function Evaluation chair did it reach significance. This included significant improvements in the contralateral extremity as well, which suggests an overall deconditioning with CLI that improves once successful revascularization
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occurs, allowing improvements in both legs. Isometric movements are more subtle than walking, balance, or power measurements involving gross movement. Isometric strength is also perhaps more pertinent to the activities of a patient with CLI, who may actually spend very little time walking but needs the ability to perform minor motions, such as comfortably adjusting positions in a bed or chair, that rely on isometric strength. These data were prospectively obtained, which is a strength of this study in comparison to other functional assessment tools. Data on the timed walk, accelerometer, and quality of life assessment are similar to those of Gardner and Killewich,29 who likewise found nonstatistical improvements in the functional test results but significant improvements in quality of life. This study differs in the inclusion of isometric muscle strength evaluation. The lack of significance in this study as well as in that of Gardner and Killewich may be due to type II error from small sample size. It is certainly possible that significance would be achieved in a larger sample size. Alternatively, evaluations based on walking, although potentially useful for patients undergoing treatment for intermittent claudication, may be unsuitable for the patients with CLI. The weakness of this study lies in its small sample size. Before the study, we performed a power analysis based on an expected standard deviation of the difference between the 6-minute walk results before and after intervention, which suggested that 96 patients would need to be recruited to detect a difference of 50 meters with 80% power at a significance of .05. One of the lessons learned from this study was the difficulty in evaluating the group of patients with CLI. The battery of tests used in this study took between 2 and 3 hours to complete. Many patients refused participation in the study because of the time commitment. It is therefore possible that we have overestimated the actual functional recovery of all patients with CLI by selecting a group that was most highly motivated and compliant with follow-up. The short follow-up interval (mean, 4 months) may also be perceived as a weakness of this study. Our intent was to observe patients out to 1 year, but the demands of the testing proved to be too great on the subjects to allow longer follow-up. However, in both the Bypass vs Angioplasty in Severe Ischaemia of the Leg (BASIL)30 and PREVENT III trials, quality of life improvements at 3 months did not change significantly out to 1 year of follow-up; therefore, it is reasonable to extrapolate a similar course in this patient cohort. National trends in lower extremity revascularization demonstrate a gradual decrease in the number of surgical revascularizations with a sharp upswing in the number of endovascular revascularizations. Currently, the results of endovascular revascularization are primarily reported in terms of patency and limb salvage, a reversion to the initial measures used to determine success of leg bypasses, with few endovascular trials focusing on functional outcomes. The results of the BASIL trial indicated equal gains in quality of life in the surgery and endovascular group out to
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1 year.30 Likewise, Taylor31 demonstrated similar clinical success regardless of revascularization method, with patient demographic factors, such as end-stage renal disease, hyperlipidemia, diabetes, and preoperative functional status, playing a greater role in determining postoperative functional status than method of revascularization. It is clear that quality of life and functional assessment will need to become an integral part of results reporting for endovascular procedures32 as well as to patients receiving best medical therapy, and the measures used in this study are readily adaptable to assessment of this group. Measurement of isometric muscle strength is informative but may not be practical for widespread use. It requires specialized equipment that may not be widely available outside of the research setting, but in this regard, we have found it very useful. Although it would be premature on the basis of this small study to conclude that isometric strength measurement should be a part of clinical trials for CLI, it clearly merits further study and could potentially be used as a marker for functional and quality of life improvements. However, a larger scale study using the much simpler methods of assessment, such as hallway walking, walking speed, balance, and standing, would be useful to demonstrate if these measures are indeed significant in a larger patient population. Likewise, the accelerometer is a useful method of assessing community functioning, but compliance is an issue that is difficult to assess or to prove. CONCLUSIONS Successful bypass for CLI results in significant improvements in patient-perceived quality of life with use of a disease-specific questionnaire (VascuQol) and in the pain domain of the SF-36. Of the functional parameters assessed, isometric strength of multiple muscle groups in both the treated and contralateral leg showed the only statistically significant improvement in this small patient cohort. Whereas more research is necessary in larger patient groups and with longer follow-up, isometric muscle measurements should be considered for use as an outcome measure in clinical trials of revascularization for CLI. AUTHOR CONTRIBUTIONS Conception and design: GL Analysis and interpretation: GL, NE Data collection: GL, NE, JL Writing the article: GL, NE Critical revision of the article: GL, AA, TL, EM, GM Final approval of the article: GL, AA, TL, EM, GM Statistical analysis: GL, NE Obtained funding: GL Overall responsibility: GL REFERENCES 1. Abouzamzam AM, Lee RW, Moneta GL, Taylor LM, Porter JM. Functional outcome after infrainguinal bypass for limb salvage. J Vasc Surg 1997;25:287-97.
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2. Nicoloff AD, Taylor LM, McLafferty RB, Moneta GL, Porter JM. Patient recovery after infrainguinal bypass grafting for limb salvage. J Vasc Surg 1998;27:256-66. 3. Management of peripheral arterial disease (PAD): TransAtlantic InterSociety Consensus (TASC). J Vasc Surg 2000;31:S190. 4. Landry GJ. Functional outcome of critical limb ischemia. J Vasc Surg 2007;45:A141-8. 5. Peeters P, Mets T. The six-minute walk as an appropriate exercise test in elderly patients with chronic heart failure. J Gerontol Med Sci 1996;51:M147-51. 6. Montgomery PS, Gardner AW. The clinical utility of a six-minute walk test in peripheral arterial occlusive disease patients. J Am Geriatr Soc 1998;46:706-11. 7. McDermott MM, Ades PA, Dyer A, Guralnik JM, Kibbe M, Criqui MH. Corridor-based functional performance measures correlate better with physical activity during daily life than treadmill measures in persons with peripheral arterial disease. J Vasc Surg 2008;48:1231-7. 8. Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, et al. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 1994;49: M85-94. 9. Guralnik JM, Ferrucci L, Simonsick EM, Salive ME, Wallace RB. Lower extremity function in persons over 70 years as a predictor of subsequent disability. N Engl J Med 1995;332:556-61. 10. Lin MR, Hwang HF, Hu MH, Wu HDIW, Wang YW, Huang FC. Psychometric comparisons of the timed up and go, one-leg stand, functional reach, and Tinetti balance measures in community-dwelling older people. J Am Geriatr Soc 2004;52:1343-8. 11. McDermott MM, Mehta S, Liu K, Guralnik JM, Martin GJ, Criqui MH, et al. Leg symptoms and the ankle brachial index independently predict patient reported walking ability in peripheral arterial disease patients without limb-threatening ischemia. J Gen Intern Med 1999;14:173-81. 12. Richardson MT, Leon AS, Jacobs DR, Ainsworth BE, Serfass R. Ability of the Caltrac accelerometer to assess daily physical activity levels. J Cardiopulm Rehabil 1995;15:107-13. 13. McDermott MM, Liu K, O’Brien E, Guralnik JM, Criqui MH, Martin GJ, et al. Monitoring physical activity in peripheral arterial disease: a comparison of two physical activity questionnaires with an accelerometer. Angiology 2000;51:91-100. 14. Morgan MBF, Crayford T, Murrin B, Fraser SCA. Developing the vascular quality of life questionnaire: a new disease-specific quality of life measure for use in lower limb ischemia. J Vasc Surg 2001;33: 679-87. 15. McDermott MM, Greenland P, Guralnik JM, Liu K, Criqui MH, Pearce WH, et al. Depressive symptoms and lower extremity functioning in men and women with peripheral arterial disease. J Gen Intern Med 2003;18:461-7. 16. Pomposelli FB, Arora S, Gibbons GW, Frykberg R, Smakowski P, Campbell DR, et al. Lower extremity arterial reconstruction in the very elderly: successful outcome preserves not only the limb but also residential status and ambulatory function. J Vasc Surg 1998;28: 215-25. 17. Seabrook GR, Cambria RA, Freischlag JA, Towne JB. Health-related quality of life and functional outcome following arterial reconstruction for limb salvage. Cardiovasc Surg 1999;7:279-86. 18. Landry GJ, Moneta GL, Taylor LM, Edwards JM, Yeager RA. Comparison of procedural outcomes after lower extremity reversed vein grafting and secondary revisions. J Vasc Surg 2003;38:22-8. 19. Taylor SM, Kalbaugh CA, Blackhurst DW, Cass AL, Trent EA, Langan EM, et al. Determinants of functional outcome after revascularization for critical limb ischemia: an analysis of 1000 consecutive vascular interventions. J Vasc Surg 2006;44:747-56. 20. Simons JP, Goodney PP, Nolan BW, Cronenwett JL, Messina LM, Schanzer A. Failure to achieve clinical improvement despite graft patency in patients undergoing infrainguinal lower extremity bypass for critical limb ischemia. J Vasc Surg 2010;51:1419-24. 21. Taylor SM, Cull DL, Kalbaugh CA, Cass AL, Harmon SA, Langan EM, et al. Critical analysis of clinical success after surgical
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extremity peripheral arterial disease. J Am Geriatr Soc 2009;57: 2246-52. McDermott MM, Liu K, Tian L, Guralnik JM, Criqui MH, Liao Y, et al. Calf muscle characteristics, strength measures, and mortality in peripheral arterial disease. J Am Coll Cardiol 2012;59:1159-67. Gardner AW, Killewich LA. Lack of functional benefits following infrainguinal bypass in peripheral arterial occlusive disease patients. Vasc Med 2001;6:9-14. Forbes JF, Adam DJ, Bell J, Fowkes FGR, Gillespie I, Raab GM, et al. Bypass versus angioplasty in severe ischaemia of the leg (BASIL) trial: health-related quality of life outcomes, resource utilization, and costeffectiveness. J Vasc Surg 2010;51:43S-51S. Taylor SM, York JW, Cull DL, Kalbaugh CA, Cass AL, Langan EM. Clinical success using patient-oriented outcome measures after lower extremity bypass and endovascular intervention for ischemic tissue loss. J Vasc Surg 2009;50:534-41. Conte MS, Geraghty PJ, Bradbury AW, Hevelone ND, Lipsitz SR, Moneta GL, et al. Suggested objective performance goals and clinical trial design for evaluating catheter-based treatment of critical limb ischemia. J Vasc Surg 2009;50:462-73.
Submitted Nov 15, 2013; accepted Jan 29, 2014.
Objective measurement of lower extremity function and quality of life after surgical revascularization for critical lower extremity ischemia Gregory J. Landry, MD, Nick O. Esmonde, BS, Jason R. Lewis, BS, Amir F. Azarbal, MD, Timothy K. Liem, MD, Erica L. Mitchell, MD, and Gregory L. Moneta, MD, Portland, Ore Background: Outcomes of revascularization for critical limb ischemia (CLI) have historically been patency, limb salvage, and survival. Functional status and quality of life have not been well described. This study used functional and quality of life assessments to measure patient-centered outcomes after revascularization for CLI. Methods: The study observed 18 patients (age, 65 6 11 years) prospectively before and after lower extremity bypass for CLI. Patients completed the Short Physical Performance Battery, which measures walking speed, leg strength, and balance, as well as performed a 6-minute walk, and calorie expenditure was measured by an accelerometer. Isometric muscle strength was assessed with the Muscle Function Evaluation chair (Metitur, Helsinki, Finland). Quality of life instruments included the 36-Item Short Form Health Survey and the Vascular Quality of Life questionnaire. Patients’ preoperative status was compared with 4-month postoperative status. Results: Muscle Function Evaluation chair measurements of ipsilateral leg strength demonstrated a significant increase in knee flexion from 64 6 62 N to 135 6 133 N (P [ .038) and nearly significant increase in knee extension from 120 6 110 N to 186 6 85 N (P [ .062) and ankle plantar flexion from 178 6 126 N to 267 6 252 N (P [ .078). In the contralateral leg, knee flexion increased from 71 6 96 N to 149 6 162 N (P [ .028) and knee extension from 162 6 112 N to 239 6 158 N (P [ .036). Absolute improvements were noted in 6-minute walk distance, daily calorie expenditure, and individual domains and overall Short Physical Performance Battery scores, and upper extremity strength decreased, although none were significant. The Vascular Quality of Life questionnaire captured significant improvement in all individual domains and overall score (P < .015). Significant improvement was noted only for bodily pain (P [ .011) on the 36-Item Short Form Health Survey. Conclusions: Despite lack of statistical improvement in most functional test results, revascularization for CLI results in improved patient-perceived leg function. Significant improvements in isometric muscle strength may explain the measured improvement in quality of life after revascularization for CLI. (J Vasc Surg 2014;-:1-7.)
Peripheral arterial disease (PAD) has become increasingly prevalent in this country as the population ages and the accumulation of risk factors, such as diabetes and smoking, is manifested. A fraction of patients with PAD will progress to critical limb ischemia (CLI) and will often require an intervention to salvage the limb. The success of an intervention has historically been oriented toward assessment of the results of the operation (ie, procedural patency and limb salvage), without considering how the operation affects patients in their daily lives. Subsequent studies have investigated the effects of surgery on self-
From the Division of Vascular Surgery, Knight Cardiovascular Institute, Oregon Health & Science University. Dr Landry is sponsored by NIH/NHLBI K23 HL80232-01. Author conflict of interest: none. Presented at the Thirty-ninth Annual Symposium of the Society for Clinical Vascular Surgery, Orlando, Fla, March 16-19, 2011. Reprint requests: Gregory J. Landry, MD, Associate Professor of Surgery, Division of Vascular Surgery, Knight Cardiovascular Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, OP11, Portland, OR 97239-3098 (e-mail: [email protected]). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a conflict of interest. 0741-5214/$36.00 Copyright Ó 2014 by the Society for Vascular Surgery. http://dx.doi.org/10.1016/j.jvs.2014.01.067
reported ambulatory and living status,1,2 which, although important end points, still do not completely address patients’ physical functioning and quality of life. Treatment of peripheral vascular disease carries a significant burden for the patient and health care system alike. The paucity of literature on functional outcomes for this group led the TransAtlantic Inter-Society Consensus to state that “specific instruments capable of detecting improvement in functional status in this [CLI] population must be developed.”3 At present, there is no consensus on the appropriate tools for assessing functional and quality of life outcomes for patients who undergo a limb salvage procedure for CLI. A previous review discussed how quality of life questionnaires and functional measurements that had been validated for PAD could be adapted for patients with CLI for assessment of changes occurring during the preoperative and postoperative interval.4 These included previously validated questionnaires (36-Item Short Form Health Survey [SF-36], Vascular Quality of Life [VascuQol], and Geriatric Depression Scale) and a battery of physical tests including timed 6-minute walk, summary performance test (chair raises, balance, and 4-meter walk), daily calorie expenditure, and upper and lower extremity isometric muscle strength measured by the Muscle Function Evaluation chair (Metitur, Helsinki, Finland). This paper describes 1
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our experience with a mix of self-reported and objective assessment tools in a cohort of patients enrolled in a longitudinal study for outcomes after surgical intervention for CLI. METHODS The study was approved by the Institutional Review Board at the Oregon Health & Science University. Patients were recruited from the vascular surgery clinic at the Oregon Health & Science University. Study entry was offered to all patients undergoing surgical bypass for CLI from January 2007 to January 2009. Patients who were nonambulatory before the onset of CLI were excluded. All patients underwent standard vascular bypasses with autogenous conduit. Functional and quality of life assessments were performed preoperatively and at approximately 4 months postoperatively, depending on patients’ ability to return to the investigation site. A series of functional assessments were performed by tests previously validated in the population of patients with PAD, although not specifically for patients with CLI. Walking distance. The timed 6-minute walk has been validated as a means to evaluate leg function and exercise capacity in the elderly and PAD populations.5,6 The test is performed in a 100-foot-long flat hallway. Patients are instructed to walk back and forth as far as they can in 6 minutes. Trained personnel walk directly behind the subjects and give standardized instructions of encouragement at set intervals. Subjects determine their own pace and stop and rest, if needed. The total distance covered is recorded in linear meters. Because subjects are allowed to walk at their own pace, results of a 6-minute walk are a more accurate reflection of walking abilities, and the test is less anxiety-provoking than treadmill walking.7 Summary performance score. The summary performance score is derived from three tests: a timed 4-meter walk, the Tinetti balance test, and a timed test of muscle power in which patients stand and sit repetitively five times. These tests have been validated in a number of populations, such as stroke and geriatric patients.8,9 The timed 4-meter walk consists of two separate trials in which the patient walks in a straight line at a brisk pace for 4 meters. The faster of the two trials is recorded. The Tinetti balance equation is a well-established assessment of balance in predicting mobility in the elderly as well as in functionally impaired patients.10 Patients stand with their feet in three separate positions: side by side, in semi-tandem, and in tandem. Scores are assigned on the basis of the number of seconds that patients can hold each position, from 0 to 10 seconds. The sit-stand test is a validated test for muscle strength and function in the elderly and is predictive of need for nursing home care.8,9 Patients begin seated and are timed while they perform five repetitions of standing and sitting down. For each task, a score (1-4, with 4 being the highest) is assigned, and the cumulative score is tabulated according to an established scoring rubric. Physical activity. The Caltrac vertical accelerometer is a validated measure of physical activity and is used to
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estimate daily activity level. Patients wore the accelerometer for 5 days, and their daily activity was calculated as a total calorie expenditure and averaged to estimate a daily expenditure. This value approximates patient function outside of the clinic, in the setting of daily life and in the community.11-13 Isometric muscle strength. The Muscle Function Evaluation chair was designed for use in the setting of physical rehabilitation and fitness training. Transducers measure isometric strength in newtons in multiple muscle groups Patients were seated upright in the chair with one extremity strapped into the chair at a time. Adjustable seat back and arm and leg restraints allowed the chair to be fitted individually, such that muscle function could be evaluated in the most comfortable position. There are four force transducers located on the chair that measure strength at the elbow, knee, and talocrural joints as well as hand grip strength with isometric muscle contractions. Patients had 10 seconds to generate their maximum force possible, with 10-second rest periods in between. The largest value during those 10 seconds was recorded as a peak force in newtons. Upper extremity function was evaluated in addition to lower extremity function as a surrogate evaluation of overall postoperative deconditioning. Quality of life questionnaires. A number of selfadministered questionnaires are available to assess generalized and disease-specific quality of life. A combination of the two types of questionnaires is often employed to capture quality of life impairment due to a specific disease process vs overall quality of life. The SF-36 is widely used as a generalized quality of life assessment and has been thoroughly validated for use in patients with PAD and to a lesser extent in groups of patients with CLI. The SF-36 considers eight categories of health: physical function, role limitation due to physical problems, bodily pain, general health perception, social function, emotional wellbeing, and role limitation due to emotional well-being. The VascuQoL questionnaire was included to capture disease-specific health parameters. The VascuQoL asks 25 questions falling into five broad categories: pain, activity, emotion, symptoms, and social. Each category is scored from 1 to 7 points, with 7 being the highest, and the total is averaged for the five categories to give a summary score.14 Finally, the Geriatric Depression Scale was used in this setting on the basis of association between depressive symptoms and decline in function.15 Scores range from 1 to 15, based on the number of statements about personal health with which the patient agrees. A score above 5 is generally considered to indicate depressive symptoms. Study participation was offered to all eligible patients undergoing surgical revascularization for CLI. Exclusion criteria included nonambulatory status predating the onset of CLI and non-English speakers. Preoperative and postoperative data were compared by a paired t-test for continuous, normally distributed data and the Mann-Whitney U test for ordinal data. Statistical significance was determined at the P < .05 level.
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Table I. Demographic data of the study cohort of 18 patients and 42 nonparticipants Factor Gender, % male Mean age at surgery 6 SD, years Indication Rest pain Ulcer or gangrene Diabetes Hypertension Coronary artery disease Smoking history Hypercholesterolemia Renal insufficiency (Cr > 1.5) Dialysis dependence COPD Previous ipsilateral bypass Type of bypass Femoral-popliteal Femoral-tibial Popliteal-pedal
Study patients (n ¼ 18)
Nonparticipants (n ¼ 42)
Significance
67% 65 6 11
71% 66 6 14
NS NS NS
33% 67% 67% 72% 44% 72% 78% 11% 6% 17% 39%
45% 55% 48% 83% 48% 62% 52% 17% 7% 14% 55%
39% 50% 11%
29% 64% 7%
NS NS NS NS NS NS NS NS NS NS
COPD, Chronic obstructive pulmonary disease; Cr, creatinine; NS, not significant; SD, standard deviation.
RESULTS During the study period, 18 subjects were enrolled and completed both preoperative and postoperative assessments. Six patients had rest pain, whereas 12 had ulcers or gangrene. All underwent vein bypass with autologous conduit (7 femoralebelow-knee popliteal, 9 femoraltibial, 2 popliteal-pedal). Five patients underwent digital amputations during the follow-up period, all of which healed, with no major amputations. The mean length of follow-up at the second evaluation was 121 6 57 days. During the same period, 60 bypasses were performed in eligible patients. Six patients enrolled and completed the preoperative assessment but refused the postoperative assessment; 36 declined participation. Incomplete participants and nonparticipants cited travel distance and time commitment as reasons for refusal. There were no demographic differences between participants and nonparticipants (Table I). There was a significant increase in ankle-brachial index (ABI) of the treated extremity after surgery (0.46 6 0.17 preoperatively, 0.86 6 0.21 postoperatively; P < .001). The contralateral ABI was unchanged after surgery (0.70 6 0.22 preoperatively, 0.76 6 0.16 postoperatively). All grafts remained patent and no subjects died during the study period. The results of the functional studies are presented in Table II. There was numerical improvement in all of the parameters tested (daily calorie expenditure, 6-minute walking distance, 4-meter walking score, Tinetti standing balance score, repeated chair rises, and overall summary performance score); however, none reached statistical significance. In contrast, significant improvement was noted in multiple measurements of isometric muscle strength in both the surgical and contralateral extremities (Tables III and IV). In the ipsilateral leg, knee flexion improved significantly from 64 6 62 N preoperatively to 135 6 133 N
Table II. Functional measurements before and after lower extremity bypass for CLI Assessment Daily physical activity, calories Six-minute walk distance, meters Four-meter walk scorea Standing balancea Chair risesa Overall SPPB scorea
Preoperative
Postoperative
1773 6 1786 2064 6 1201 97 6 88 2.43 2.36 1.47 6.36
6 6 6 6
1.4 1.8 1.4 4
P value .313
128 6 75
.216
6 6 6 6
.849 .510 .417 .849
2.50 2.86 2.00 7.21
1.5 1.5 1.7 4
CLI, Critical limb ischemia; SPPB, Short Physical Performance Battery. a Scored 0 to 4. Overall score, 0 to 12: 0, worst; 12, best (reported as mean 6 standard deviation). Each measurement scored is based on established quartiles for the elderly population.
Table III. Lower extremity isometric muscle strength in the treated extremity Ipsilateral measurement
Preoperative
Ankle dorsiflexion Ankle plantar flexion Knee flexion Knee extension
124 178 64 120
6 6 6 6
87 126 62 110
Postoperative
P value
6 6 6 6
.826 .078 .038 .062
130 267 135 186
98 252 133 85
Reported in newtons (mean 6 standard deviation).
postoperatively (P ¼ .038). Strong trends toward improvement were also noted in ankle plantar flexion (178 6 126 N preoperatively vs 267 6 252 N postoperatively; P ¼ .078) and knee extension (120 6 110 N vs 186 6 85 N; P ¼ .062). Significant improvements were also noted in the contralateral limb in knee flexion (71 6 96 N preoperatively vs 149 6 162 N postoperatively; P ¼ .028) and knee extension (162 6 112 N preoperatively vs 239 6 158 N postoperatively; P ¼ .036). No significant changes in upper extremity function were noted (Table V).
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Table IV. Lower extremity isometric muscle strength in the contralateral extremity
Table VI. Quality of life before and after surgery (generalized, not disease specific)
Contralateral measurement Preoperative Postoperative P value Ankle dorsiflexion Ankle plantar flexion Knee flexion Knee extension
163 252 71 162
6 6 6 6
109 182 96 112
150 292 149 239
6 6 6 6
SF-36 93 252 162 158
.624 .368 .028 .036
Reported in newtons (mean 6 standard deviation).
Table V. Upper extremity isometric muscle strength Upper extremity measurement
Preoperative
Right elbow flexion Left elbow flexion Right elbow extension Left elbow extension Right hand grip Left hand grip
160 114 118 108 266 261
6 6 6 6 6 6
97 74 63 77 140 149
Postoperative
P value
6 6 6 6 6 6
.322 .272 .662 .981 .199 .253
143 137 109 107 236 220
64 74 60 61 128 138
Reported in newtons (mean 6 standard deviation).
In the generalized quality of life questionnaire (SF-36), a significant improvement was seen only in the domain of bodily pain (preoperative score, 25 6 19; postoperative score, 45 6 21; P ¼ .001), with a strong trend toward improvement in role limitations due to physical health (preoperative score, 4 6 13; postoperative score, 29 6 42; P ¼ .067). No differences were noted in the domains of physical functioning, general health, vitality, social functioning, role limitations due to emotional problems, or mental health (Table VI). In the disease-specific quality of life questionnaire (VascuQol), significant improvements were noted in all domains and in the total score (Table VII). There was no significant change in the Geriatric Depression Scale score (preoperative score, 4.1 6 3.8; postoperative score, 4.9 6 2.9; P ¼ .394). Four subjects (22.2%) had clinically significant depression scores ($6), with no significant change after revascularization. DISCUSSION Assessment of functional outcomes of surgical revascularization for CLI has undergone a significant evolution in the past two decades. For many years, the outcomes of surgical revascularization for CLI were reported as graft patency, limb salvage, and survival. These remain important parameters as good leg function is dependent on optimal perfusion. However, graft patency tends to be a “lesion-oriented” outcome measure and may not reflect how well a patient is performing functionally. In the 1990s, the emphasis of outcomes reporting shifted to more “patient-oriented” outcomes.1,2 Ambulatory status and living status (ie, independent vs nonindependent living) were reported, and self-reported quality of life assessments became standard reporting measures. Numerous studies
Physical functioning Role limitations due to physical health Bodily pain General health Vitality Social functioning Role limitations due to emotional problems Mental health
Preoperative scorea
Postoperative scorea
P value
30 6 23 4 6 13
45 6 30 29 6 42
.172 .067
6 6 6 6 6
21 14 19 27 43
.001 .36 .532 .151 .675
76 6 14
.246
25 49 42 47 57
6 6 6 6 6
19 21 19 28 50
69 6 19
45 54 46 58 65
SF-36, 36-Item Short Form Health Survey. a Scored 0 to 100 (reported mean 6 standard deviation): 0, worst; 100, best.
Table VII. Quality of life before and after surgery (disease specific) VascuQol Activity Symptoms Pain Emotional Social Total score
Preoperative scorea 2.32 3.35 2.53 3.60 2.84 2.93
6 6 6 6 6 6
0.95 1.38 1.06 1.33 1.50 0.93
Postoperative scorea
P value
6 6 6 6 6 6
.001 .001 .002 .014 .001 .001
4.04 5.22 4.45 5.06 5.09 4.66
1.44 1.14 1.83 1.37 1.45 1.28
VascuQol, Vascular Quality of Life questionnaire. a Scored 1 to 7 (reported mean 6 standard deviation): 1, worst; 7, best.
have subsequently confirmed functional improvements in the majority of patients on the basis of these measures.16-19 However, graft patency does not always translate to good function. A recent study from the Vascular Surgery Group of New England demonstrated that 10% of patients experienced clinical failure at 1 year after bypass, defined as amputation or worsening ischemia, despite having a patent graft.20 Taylor21 defined clinical success as graft patency to the point of wound healing, limb salvage, and ambulation for 1 year after bypass and survival for 6 months. Only 44% of 331 consecutive bypass patients were able to achieve clinical success. The use of ambulatory status and living status as outcome measures makes assumptions that may not be true for all patients. Whereas independent ambulation is a desirable outcome to preserve, as a binary variable it leaves many unanswered questions about the duration or quality of ambulation, and it does not assess how patients perform in their activities of daily living. Kumar22 demonstrated that although revascularization allowed preservation of ambulatory function, only 53% of working patients were able to return to their original work. Likewise, whereas independent living is preferable for most people, a high level of functionality is certainly possible in an assisted living environment. Self-reported quality of life questionnaires also are inherently flawed in that they rely on patients’ perceptions and
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recollections and may not accurately reflect actual function. As stated by the Nobel Prize-winning psychologist Daniel Kahneman, when one is asked about quality of life, “A few ideas that are relevant to the question will occur to you; many others will not . the score that you quickly assign to your life is determined by a small sample of highly available ideas, not by a careful weighting of the domains of your life.”23 The lack of a validated functional assessment tool to evaluate interventions for CLI was cited in the TransAtlantic Inter-Society Consensus I document as a critical issue for further research. In this study, we used a battery of functional assessments that have previously been used extensively in the assessment of geriatric patients, although not specifically to assess the results of intervention. Quality of life improvements after successful revascularization were noted in this patient population. All domains of the VascuQol demonstrated significant improvements at 4 months, as did the aggregate score. In the SF-36 analysis, only the pain domain showed significant improvement. These findings are in line with numerous previous studies that have shown similar improvements in selfreported quality of life with use of a variety of general and disease-specific quality of life measures, the largest of which, the Prevention of Recurrent Venous Thromboembolism (PREVENT) III trial, examined more than 1400 subjects.24 In contrast, Cieri et al,25 using the Katz index, noted a significant decline in the ability to perform activities of daily living after both surgical and endovascular revascularization, despite successful limb preservation and improvements in pain relief and tissue healing. McDermott et al15 noted a high prevalence of depressive symptoms in patients with symptomatic PAD, with 21.7% of patients exhibiting significant depressive symptoms and a greater number of depressive symptoms associated with greater impairment of lower extremity function. In our study, a similar percentage of patients (22.2%) exhibited significant depressive symptoms but with no significant change after successful revascularization. Of the objective functional measures performed, the results of evaluation with the Muscle Function Evaluation chair correlated best with the self-reported quality of life findings. Isometric muscle strength has been found to be diminished in the distal extremities in patients with PAD and is correlated with diminished ABI.26 Subjects with PAD and diminished baseline muscle strength have been shown to have increased long-term functional decline and mortality.27,28 The Muscle Function Evaluation chair measures isometric muscle strength in multiple groups. How revascularization improves muscle strength is not clear. Whether actual muscle mass improves is not known. It is perhaps more likely that improvement in ischemic pain allows better performance. Whereas there was a trend toward improvement in all of the functional measures, only in the Muscle Function Evaluation chair did it reach significance. This included significant improvements in the contralateral extremity as well, which suggests an overall deconditioning with CLI that improves once successful revascularization
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occurs, allowing improvements in both legs. Isometric movements are more subtle than walking, balance, or power measurements involving gross movement. Isometric strength is also perhaps more pertinent to the activities of a patient with CLI, who may actually spend very little time walking but needs the ability to perform minor motions, such as comfortably adjusting positions in a bed or chair, that rely on isometric strength. These data were prospectively obtained, which is a strength of this study in comparison to other functional assessment tools. Data on the timed walk, accelerometer, and quality of life assessment are similar to those of Gardner and Killewich,29 who likewise found nonstatistical improvements in the functional test results but significant improvements in quality of life. This study differs in the inclusion of isometric muscle strength evaluation. The lack of significance in this study as well as in that of Gardner and Killewich may be due to type II error from small sample size. It is certainly possible that significance would be achieved in a larger sample size. Alternatively, evaluations based on walking, although potentially useful for patients undergoing treatment for intermittent claudication, may be unsuitable for the patients with CLI. The weakness of this study lies in its small sample size. Before the study, we performed a power analysis based on an expected standard deviation of the difference between the 6-minute walk results before and after intervention, which suggested that 96 patients would need to be recruited to detect a difference of 50 meters with 80% power at a significance of .05. One of the lessons learned from this study was the difficulty in evaluating the group of patients with CLI. The battery of tests used in this study took between 2 and 3 hours to complete. Many patients refused participation in the study because of the time commitment. It is therefore possible that we have overestimated the actual functional recovery of all patients with CLI by selecting a group that was most highly motivated and compliant with follow-up. The short follow-up interval (mean, 4 months) may also be perceived as a weakness of this study. Our intent was to observe patients out to 1 year, but the demands of the testing proved to be too great on the subjects to allow longer follow-up. However, in both the Bypass vs Angioplasty in Severe Ischaemia of the Leg (BASIL)30 and PREVENT III trials, quality of life improvements at 3 months did not change significantly out to 1 year of follow-up; therefore, it is reasonable to extrapolate a similar course in this patient cohort. National trends in lower extremity revascularization demonstrate a gradual decrease in the number of surgical revascularizations with a sharp upswing in the number of endovascular revascularizations. Currently, the results of endovascular revascularization are primarily reported in terms of patency and limb salvage, a reversion to the initial measures used to determine success of leg bypasses, with few endovascular trials focusing on functional outcomes. The results of the BASIL trial indicated equal gains in quality of life in the surgery and endovascular group out to
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1 year.30 Likewise, Taylor31 demonstrated similar clinical success regardless of revascularization method, with patient demographic factors, such as end-stage renal disease, hyperlipidemia, diabetes, and preoperative functional status, playing a greater role in determining postoperative functional status than method of revascularization. It is clear that quality of life and functional assessment will need to become an integral part of results reporting for endovascular procedures32 as well as to patients receiving best medical therapy, and the measures used in this study are readily adaptable to assessment of this group. Measurement of isometric muscle strength is informative but may not be practical for widespread use. It requires specialized equipment that may not be widely available outside of the research setting, but in this regard, we have found it very useful. Although it would be premature on the basis of this small study to conclude that isometric strength measurement should be a part of clinical trials for CLI, it clearly merits further study and could potentially be used as a marker for functional and quality of life improvements. However, a larger scale study using the much simpler methods of assessment, such as hallway walking, walking speed, balance, and standing, would be useful to demonstrate if these measures are indeed significant in a larger patient population. Likewise, the accelerometer is a useful method of assessing community functioning, but compliance is an issue that is difficult to assess or to prove. CONCLUSIONS Successful bypass for CLI results in significant improvements in patient-perceived quality of life with use of a disease-specific questionnaire (VascuQol) and in the pain domain of the SF-36. Of the functional parameters assessed, isometric strength of multiple muscle groups in both the treated and contralateral leg showed the only statistically significant improvement in this small patient cohort. Whereas more research is necessary in larger patient groups and with longer follow-up, isometric muscle measurements should be considered for use as an outcome measure in clinical trials of revascularization for CLI. AUTHOR CONTRIBUTIONS Conception and design: GL Analysis and interpretation: GL, NE Data collection: GL, NE, JL Writing the article: GL, NE Critical revision of the article: GL, AA, TL, EM, GM Final approval of the article: GL, AA, TL, EM, GM Statistical analysis: GL, NE Obtained funding: GL Overall responsibility: GL REFERENCES 1. Abouzamzam AM, Lee RW, Moneta GL, Taylor LM, Porter JM. Functional outcome after infrainguinal bypass for limb salvage. J Vasc Surg 1997;25:287-97.
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2. Nicoloff AD, Taylor LM, McLafferty RB, Moneta GL, Porter JM. Patient recovery after infrainguinal bypass grafting for limb salvage. J Vasc Surg 1998;27:256-66. 3. Management of peripheral arterial disease (PAD): TransAtlantic InterSociety Consensus (TASC). J Vasc Surg 2000;31:S190. 4. Landry GJ. Functional outcome of critical limb ischemia. J Vasc Surg 2007;45:A141-8. 5. Peeters P, Mets T. The six-minute walk as an appropriate exercise test in elderly patients with chronic heart failure. J Gerontol Med Sci 1996;51:M147-51. 6. Montgomery PS, Gardner AW. The clinical utility of a six-minute walk test in peripheral arterial occlusive disease patients. J Am Geriatr Soc 1998;46:706-11. 7. McDermott MM, Ades PA, Dyer A, Guralnik JM, Kibbe M, Criqui MH. Corridor-based functional performance measures correlate better with physical activity during daily life than treadmill measures in persons with peripheral arterial disease. J Vasc Surg 2008;48:1231-7. 8. Guralnik JM, Simonsick EM, Ferrucci L, Glynn RJ, Berkman LF, Blazer DG, et al. A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 1994;49: M85-94. 9. Guralnik JM, Ferrucci L, Simonsick EM, Salive ME, Wallace RB. Lower extremity function in persons over 70 years as a predictor of subsequent disability. N Engl J Med 1995;332:556-61. 10. Lin MR, Hwang HF, Hu MH, Wu HDIW, Wang YW, Huang FC. Psychometric comparisons of the timed up and go, one-leg stand, functional reach, and Tinetti balance measures in community-dwelling older people. J Am Geriatr Soc 2004;52:1343-8. 11. McDermott MM, Mehta S, Liu K, Guralnik JM, Martin GJ, Criqui MH, et al. Leg symptoms and the ankle brachial index independently predict patient reported walking ability in peripheral arterial disease patients without limb-threatening ischemia. J Gen Intern Med 1999;14:173-81. 12. Richardson MT, Leon AS, Jacobs DR, Ainsworth BE, Serfass R. Ability of the Caltrac accelerometer to assess daily physical activity levels. J Cardiopulm Rehabil 1995;15:107-13. 13. McDermott MM, Liu K, O’Brien E, Guralnik JM, Criqui MH, Martin GJ, et al. Monitoring physical activity in peripheral arterial disease: a comparison of two physical activity questionnaires with an accelerometer. Angiology 2000;51:91-100. 14. Morgan MBF, Crayford T, Murrin B, Fraser SCA. Developing the vascular quality of life questionnaire: a new disease-specific quality of life measure for use in lower limb ischemia. J Vasc Surg 2001;33: 679-87. 15. McDermott MM, Greenland P, Guralnik JM, Liu K, Criqui MH, Pearce WH, et al. Depressive symptoms and lower extremity functioning in men and women with peripheral arterial disease. J Gen Intern Med 2003;18:461-7. 16. Pomposelli FB, Arora S, Gibbons GW, Frykberg R, Smakowski P, Campbell DR, et al. Lower extremity arterial reconstruction in the very elderly: successful outcome preserves not only the limb but also residential status and ambulatory function. J Vasc Surg 1998;28: 215-25. 17. Seabrook GR, Cambria RA, Freischlag JA, Towne JB. Health-related quality of life and functional outcome following arterial reconstruction for limb salvage. Cardiovasc Surg 1999;7:279-86. 18. Landry GJ, Moneta GL, Taylor LM, Edwards JM, Yeager RA. Comparison of procedural outcomes after lower extremity reversed vein grafting and secondary revisions. J Vasc Surg 2003;38:22-8. 19. Taylor SM, Kalbaugh CA, Blackhurst DW, Cass AL, Trent EA, Langan EM, et al. Determinants of functional outcome after revascularization for critical limb ischemia: an analysis of 1000 consecutive vascular interventions. J Vasc Surg 2006;44:747-56. 20. Simons JP, Goodney PP, Nolan BW, Cronenwett JL, Messina LM, Schanzer A. Failure to achieve clinical improvement despite graft patency in patients undergoing infrainguinal lower extremity bypass for critical limb ischemia. J Vasc Surg 2010;51:1419-24. 21. Taylor SM, Cull DL, Kalbaugh CA, Cass AL, Harmon SA, Langan EM, et al. Critical analysis of clinical success after surgical
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Submitted Nov 15, 2013; accepted Jan 29, 2014.
