Objective measurement of lower extremity function and quality of life following surgical revascularization for critical lower extremity ischemia

Abstract

Background

Outcomes of revascularization for critical limb ischemia (CLI) have historically been patency, limb salvage and survival. Functional status and quality of life (QOL) have not been well described. This study utilized functional and QOL assessments to measure patient-centered outcomes following revascularization for CLI.

Methods

18 patients (age 65±11 yrs) were followed prospectively before and after lower extremity bypass for CLI. Patients completed the Short Physical Performance Battery (SPPB) which measures walking speed, leg strength and balance, as well as performing a 6 minute walk, and measuring caloric expenditure with an accelerometer. Isometric muscle strength was assessed using the Muscle Function Evaluation chair (MFEC). QOL instruments included the Short Form 36 (SF-36) and Vascular Quality of Life (VascuQol). Patients’ preoperative status was compared with four month postoperative status.

Results

MFEC measurements of ipsilateral leg strength demonstrated a significant increase in knee flexion from 64±63 Newtons (N) to 135±133N (p=0.038), and near significant increase in knee extension 120±110N to 186±85N (p=0.062) and ankle plantar flexion 178±126N to 267±252N (p=0.078). In the contralateral leg, knee flexion increased 71±96N to 149±162N (p=0.028), knee extension 162±112N to 239±158N (p=0.036). Absolute improvements were noted in 6 minute walk distance, daily caloric expenditure and in individual domains and overall SPPB scores, and upper extremity strength decreased, though none were significant. The VascuQol captured significant improvement in all individual domains, and overall score (p<0.015). Significant improvement was noted only for Body Pain (p=0.011) using the SF-36.

Conclusions

Despite lack of statistical improvement in most functional tests, revascularization for critical limb ischemia results in improved patient perceived leg function. Significant improvements in isometric muscle strength may explain the measured improvement in quality of life following revascularization for CLI.

Introduction

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, manifests. A fraction of patients with PAD will progress to critical limb ischemia (CLI) and will often require an intervention to salvage their limb. The success of an intervention has historically been oriented towards assessing the results of the operation, i.e., procedural patency and limb salvage, without considering how the operation affects the patient in their daily lives. Subsequent studies have investigated the effects of surgery on self-reported ambulatory and living status (1,2), which, while important endpoints, 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 Intersociety 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 limb salvage procedure for critical limb ischemia.

A previous review discussed how QOL questionnaires and functional measurements that had been validated for PAD could be adapted for patients with CLI in order to assess changes occurring during the pre- and post-operative interval (4). These included previously validated questionnaires (Short Form 36, Vascular Quality of Life (VascuQOL) and Geriatric Depression Scale (GDS) and a battery of physical tests including timed 6-minute walk, summary performance test (chair raises, balance and 4-meter walk), daily caloric expenditure and upper and lower extremity isometric muscle strength, measured by the muscle function evaluation chair. This paper describes our experience with a mix of self-reported and objective assessment tools in a cohort of patients enrolled in a longitudinal study for outcomes following surgical intervention for critical limb ischemia.

Methods

The study was approved by the Institutional Review Board at the Oregon Health & Science University (OHSU). Patients were recruited from the vascular surgery clinic at OHSU. Study entry was offered to all patients undergoing surgical bypass for critical limb ischemia from January 2007 to January 2009. Patients who were nonambulatory prior to 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 was performed, utilizing tests previously validated in the population of patients with peripheral arterial disease, 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 six 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. Since subjects are allowed to walk at their own pace, results of a six minute walk are a more accurate reflection of walking abilities as well as being 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 where 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 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 based on the number of seconds that patients can hold each position, from 0–10 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 cumulative score is tabulated according to an established scoring rubric.

Physical activity

The Caltrac vertical accelerometer is a validated measured of physical activity and is used to estimate daily activity level. Patients wore the accelerometer for five days and their daily activity was calculated as a total caloric expenditure, and averaged to estimate a daily expenditure. This value approximates patient function outside of the clinic, in the setting of their daily life and community (11–13).

Isometric Muscle strength

The Muscle Function Evaluation (MFE) chair (Metitur, Helsinki, Finland) 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, arm and leg restraints allowed for the chair to be fitted individually, such that their muscle function could be evaluated in their 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 ten seconds to generate their maximum force possible, with ten second rest periods in between. The largest value during those ten 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 self-administered questionnaires are available for assessing 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, versus overall quality of life. The Short Form 36 (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 well-being and role limitation due to emotional well-being.

The Vascular Quality of Life Questionnaire (VascuQoL) was included to capture disease-specific health parameters. The VascuQoL asks twenty five questions, falling into five broad categories: Pain, Activity, Emotion, Symptoms and Social. Each category is scored from 1–7 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 (GDS) was used in this setting on the basis of association between depressive symptoms and decline in function (15). Scores range from 1–15, based upon the number of statements about personal health the patients agree with. 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, non-English speakers,

Pre and postoperative data were compared using 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<0.05 level.

Results

During the study period, 18 subjects were enrolled and completed both pre- and post-operative assessments.. Six patients had rest pain, while 12 had ulcers or gangrene. All underwent vein bypass with autologous conduit (7 femoral-below knee popliteal, 9 femoral-tibial, 2 popliteal-pedal). 5 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±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, while 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 1).

Table 1.

Demographic data on the study cohort of 18 patients and 42 nonparticipants

Factor	Study patients (n=18)	Nonparticipants (n=42)	Significance
Gender (% male)	67%	71%	ns
Age at surgery	65±11 years	66±14 years	ns
Indication			ns
Rest Pain	33%	45%
Ulcer/gangrene	67%	55%
Diabetes	67%	48%	ns
Hypertension	72%	83%	ns
Coronary artery disease	44%	48%	ns
Smoking history	72%	62%	ns
Hypercholesterolemia	78%	52%	ns
Renal insufficiency (Cr>1.5)	11%	17%	ns
Dialysis dependence	6%	7%	ns
COPD	17%	14%	ns
Previous ipsilateral bypass	39%	55%	ns
Type of bypass			ns
Femoral-popliteal	39%	29%
Femoral-tibial	50%	64%
Popliteal-pedal	11%	7%

There was a significant increase in ABI on the operated extremity following surgery (0.46±0.17 preop, 0.86±0.21 postop, p<0.001). Contralateral ABI were unchanged following surgery (0.70±0.22 preop, 0.76±0.16 postop). All grafts remained patent and no subjects died during the study period.

The results of the functional studies are presented in table 2. There was numerical improvement in all of the parameters tested (daily caloric 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.

Table 2.

Functional measurements before and after lower extremity bypass for CLI

Assessment	Pre-op	Post-op	P value
Daily Physical Activity (calories)	1773 ± 1786	2064 ± 1201	0.313
6 minute walk distance (meters)	97 ± 88	128 ± 75	0.216
4 meter walk score*	2.43 ± 1.4	2.50 ± 1.5	0.849
Standing balance*	2.36 ± 1.8	2.86 ± 1.5	0.510
Chair rises*	1.47 ± 1.4	2.00 ± 1.7	0.417
Overall SPPB*	6.36 ± 4	7.21 ± 4	0.849

^*Scored 0–4. Overall score 0–12: 0 = worst, 12 = best (Reported as mean ± SD). Each measurement scored based upon established quartiles for elderly population

In contrast, significant improvement was noted in multiple measurements of isometric muscle strength in both the operated and contralateral extremity (Table 3a, 3b). In the ipsilateral leg, knee flexion improved significantly from 64±62 N preoperatively to 135±133 N postoperatively (p=0.038). Strong trends toward improvement were also noted in ankle plantar flexion (178 ± 126 N preop vs. 267 ± 252 N postop, p =0.078) and knee extension (120 ± 110 vs. 186 ± 85, p=0.062). Significant improvements were also noted in the contralateral limb in knee flexion (71 ± 96 N preop vs. 149 ± 162 N postop, p=0.028) and knee extension (162 ± 112 N preop vs. 239 ± 158 N postop, p=0.036). No significant changes in upper extremity function were noted (Table 4).

Table 3a.

Lower extremity isometric muscle strength in the operated extremity

Ipsilateral measurement	Pre-op	Post-op	P value
Ankle dorsiflexion	124 ± 87	130 ± 98	0.826
Ankle plantar flexion	178 ± 126	267 ± 252	0.078
Knee flexion	64 ± 62	135 ± 133	0.038
Knee extension	120 ± 110	186 ± 85	0.062

Reported in Newtons (mean±SD)

Table 3b.

Lower extremity isometric muscle strength in the contralateral extremity

Contralateral Measurement	Pre-op	Post-op	P value
Ankle dorsiflexion	163 ± 109	150 ± 93	0.624
Ankle plantar flexion	252 ± 182	292 ± 252	0.368
Knee flexion	71 ± 96	149 ± 162	0.028
Knee extension	162 ± 112	239 ± 158	0.036

Reported in Newtons (mean±SD)

Table 4.

Upper extremity isometric muscle strength

Upper Extremity Measurement	Pre-op	Post-op	P value
Right elbow flexion	160 ± 97	143 ± 64	0.322
Left elbow flexion	114 ± 74	137 ± 74	0.272
Right elbow extension	118 ± 63	109 ± 60	0.662
Left elbow extension	108 ± 77	107 ± 61	0.981
Right hand grip	266 ± 140	236 ± 128	0.199
Left hand grip	261 ± 149	220 ± 138	0.253

Reported in Newtons (mean±SD)

In the generalized quality of life questionnaire (SF36), a significant improvement was seen only the domain of body pain (preop score 25±19, postop score 45±21, p=0.001) with a strong trend toward improvement in role limitations due to physical health (preop score 4±13, postop score 29±42, p=0.067). 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 5).

Table 5.

Quality of life before and after surgery (generalized, not disease specific)

Short Form 36 questionnaire (SF36)	Pre-op score*	Post-op score*	P value
Physical functioning	30 ± 23	45 ± 30	0.172
Role limitations due to physical health	4 ± 13	29 ± 42	0.067
Body Pain	25 ± 19	45 ± 21	0.001
General health	49 ± 21	54 ± 14	0.36
Vitality	42 ± 19	46 ± 19	0.532
Social functioning	47 ± 28	58 ± 27	0.151
Role limitations due to emotional problems	57 ± 50	65 ± 43	0.675
Mental health	69 ± 19	76 ± 14	0.246

^*scored 0–100 (reported mean ± SD) 0 = worst, 100 = best

In the disease specific quality of life questionnaire (VASCUQOL), significant improvements were noted in all domains and in the total score (Table 6). There was no significant change in the Geriatric Depression Scale score (preop score 4.1±3.8 vs. postop score 4.9±2.9, p=0.394). Four subjects (22.2%) had clinically significant depression scores (=6), with no significant change following revascularization.

Table 6.

Quality of life before and after surgery (disease specific)

Vascular Quality of Life Questionnaire (VascuQol)	Pre-op score*	Post-op score*	P value
Activity	2.32 ± 0.95	4.04 ± 1.44	0.001
Symptoms	3.35 ± 1.38	5.22 ± 1.14	0.001
Pain	2.53 ± 1.06	4.45 ± 1.83	0.002
Emotional	3.60 ± 1.33	5.06 ± 1.37	0.014
Social	2.84 ± 1.50	5.09 ± 1.45	0.001
Total score	2.93 ± 0.93	4.66 ± 1.28	0.001

^*Scored 1–7 (reported mean ± SD) 1 = worst, 7 = best

Discussion

Assessment of functional outcomes of surgical revascularization for critical limb ischemia has undergone a significant evolution in the past two decades. For many years the outcomes of surgical revascularization for critical limb ischemia 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 1990’s, the emphasis of outcomes reporting shifted to more “patient oriented” outcomes (1,2). Ambulatory and living status (i.e., independent vs. nonindependent living) were reported, and self-reported quality of life assessments became standard reporting measures. Numerous studies have subsequently confirmed functional improvements in the majority of patients based on 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 one year post-bypass, defined as amputation or worsening ischemia, despite having a patent graft (20). Taylor defined clinical success as graft patency to the point of wound healing, limb salvage and ambulation for one year post-bypass, and survival for 6 months. Only 44% of 331 consecutive bypass patients were able to achieve clinical success (21).

The use of ambulatory and living status as outcome measures makes assumptions that may not be true for all patients. While 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 does not assess how patients perform in their activities of daily living. Kumar demonstrated that although revascularization allowed preservation of ambulatory function, only 53% of working patients were able to return to their original work (22). Likewise, while 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 recollections and may not accurately reflect actual function. As stated by the Nobel Prize winning psychologist Howard 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 critical limb ischemia was cited in the TASC 1 document as a critical issue for further research. In this study we utilized a battery of functional assessments that have previously been used extensively in the assessment of geriatric patients, although not specifically used to assess the results of intervention.

Quality of life improvements following successful revascularization were noted in this patient population. All domains of the VASCUQOL demonstrated significant improvements at four months, as well as did the aggregate score. In the SF36 analysis, only the pain domain showed significant improvement. These findings are in line with numerous previous studies, which have shown similar improvements in self-reported quality of life using a variety of general and disease-specific quality of life measures, the largest of which, the PREVENT III trial, examined over 1400 subjects (24). In contrast, Cieri, et al., using the Katz Index, noted a significant decline in the ability to perform activities of daily living following both surgical and endovascular revascularization, despite successful limb preservation and improvements in pain relief and tissue healing (25). McDermott, et al., noted a high prevalence of depressive symptoms in patients with symptomatic peripheral arterial disease, with 21.7% of patients exhibiting significant depressive symptoms, and a greater number of depressive symptoms associated with greater impairment of lower extremity function (15). In our study a similar percentage of patients (22.2%) exhibited significant depressive symptoms but with no significant change following successful revascularization.

Of the objective functional measures performed, the results of evaluation using 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 MFE 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. While there was a trend toward improvement in all of the functional measures, only in the MFE chair did it reach significance. This included significant improvements in the contralateral extremity as well, which suggests an overall deconditioning with critical limb ischemia that improves once successful revascularization 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 critical limb ischemia, 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, which 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 that of Gardner and associates, who likewise found nonstatistical improvements in the functional test but significant improvements in quality of life (29). 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 associates, 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, while potentially useful for patients undergoing treatment for intermittent claudication, may be unsuitable for the patients with critical limb ischemia.

The weakness of this study lies in its small sample size. Prior to the study we performed a power analysis based on an expected standard deviation of the difference between the pre and post intervention six minute walk, which suggested that 96 patients would need to be recruited to detect a difference of 50 meters with 80% power at a significance of 0.05. One of the lessons learned from this study was the difficulty in evaluating the group of patients with critical limb ischemia. The battery of tests used in this study took between two to three hours to complete. Many patients refused participation in the study due to the time commitment. It is therefore possible that we have overestimated the actual functional recovery of all patients with CLI by selecting a group who 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 follow patients out to one year, but the demands of the testing proved to be too great on the subjects to allow for longer follow up. However, in both the BASIL (30) and PREVENT III trials, quality of life improvements at three months did not change significantly out to one 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 revascularization. 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 one year (30). Likewise, Taylor 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 (31). It is clear that quality of life and functional assessment will need to become an integral part of results reporting for endovascular procedures (32), 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. While it would be premature based on this small study to conclude that isometric strength measurements should be a part of clinical trials for critical limb ischemia, 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 as issue that is difficult to assess or prove.

In summary, successful bypass for critical limb ischemia results in significant improvements in patient-perceived quality of life using 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 operated and nonoperated leg showed the only statistically significant improvement in this small patient cohort. While more research is necessary in larger patient groups and with longer follow up, the use of isometric muscle measurements should be considered for use as an outcome measure in clinical trials of revascularization for critical limb ischemia.