Lower limb revascularization leads to faster walking but with less efficient mechanics in claudicating patients

Abstract

Peripheral artery disease (PAD) is characterized by reduced blood flow to the extremities due to atherosclerosis. Studies report impaired gait mechanics in patients with lower extremity PAD, including reduced peak ankle power at late stance compared to healthy adults. We hypothesized that revascularization surgery would improve gait mechanics when quantified by net lower limb joint work across the stance phase of walking. We performed gait analyses in 35 patients with PAD and 35 healthy, older adults. Patients with PAD performed a walking protocol prior to and six months following revascularization surgery. Healthy adults only took part in a single walking session. Lower limb joint powers were calculated using inverse dynamics and were integrated across early, middle, and late stance phases to determine the work performed during each phase (J kg⁻¹). The work mechanical ratio between positive-producing and negative-producing phases of stance was calculated for each lower-limb joint. Self-selected walking speed significantly increased from 1.13 ± 0.2 ms⁻¹ to 1.26 ± 0.18 ms⁻¹ in patients following revascularization (p<0.001). We observed a significant decrease in positive late stance work (p<0.001) in conjunction with more negative work during early stance (p<0.001) in patients following revascularization. Revascularization surgery led to faster walking without an increase in the ankle joint’s mechanical ratio. Our results suggest faster walking was achieved via work done at the hip joint rather than the ankle joint. These findings suggest that additional therapies that facilitate the restoration of muscle, tissue, and nervous system damage caused by years of having reduced blood flow to the limbs might still be beneficial following revascularization.

Introduction

Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis that produces blockages in the arteries supplying the lower extremities (Norgren et al., 2007). Patients with PAD commonly present symptoms of intermittent claudication, an ischemic pain that impairs the muscles of the affected legs, quickly following onset of physical activity which greatly inhibits their ability to complete tasks of daily living (Gerhard-Herman et al., 2017; Hardman et al., 2014; Norgren et al., 2007). For some of these patients, revascularization surgery may be necessary to alleviate their ischemic leg pain and enable their ability to engage in physical activity (Gerhard-Herman et al., 2017; Vartanian and Conte, 2015). While the effectiveness of revascularization in reducing claudication symptoms and increasing walking distance is clear, the subsequent effects on patients’ walking mechanics following revascularization warrants further investigation (Feinglass et al., 2000).

When we walk, we accelerate and decelerate within every step (Donelan et al., 2002). These accelerations and decelerations are produced by alternating bouts of positive and negative mechanical work by the legs. Previous literature has suggested that reduced positive lower limb joint work during late stance is associated with an increase in negative lower limb joint work during early stance of walking (Huang et al., 2015). In other words, a reduced push-off results in a greater heel strike in the subsequent step. This relationship between positive and negative work may be useful for evaluating the effects of revascularization on walking mechanics in patients with PAD. Research has documented many biomechanical differences between patients with PAD and healthy adults (Koutakis et al., 2010b; Wurdeman et al., 2012a). Patients with lower limb PAD have gait mechanics that greatly differ from healthy individuals due to myopathy and muscle weakness caused by chronic, insufficient blood supply to the muscle. In particular, patients’ torque and powers about the ankle are significantly lower than their healthy counterparts (Chen et al., 2008; Koutakis et al., 2010a; Wurdeman et al., 2012b). The plantar flexor muscles are critical to healthy walking because they contribute approximately 46% of positive work during walking at a speed of 1.25ms⁻¹ and they are the most common muscle group affected by claudication symptoms in the legs of PAD patients (Farris and Sawicki, 2012). Therefore, improving blood flow to the plantar flexor muscles in patients with PAD through surgical intervention could translate to improvements in patients’ walking mechanics and their ability to complete daily living tasks. The improvement to walking mechanics may be an increase to positive work performed during late stance by the plantar flexors coupled with a decrease to negative lower limb joint work during early stance. This relationship between different phases of stance can be more easily interpreted using ratios.

Efficiency is the ratio between a system’s energy output and its input. Here, we analyzed the mechanical ratio between phases of stance that produce positive work to phases of stance that produce negative work. Positive work is the generation (e.g. forward progression) and negative work is the absorption (e.g. energy expenditure related to the slowing of joint rotations). Our analysis is similar to previously established methodologies for evaluating joint work. However, our implementation evaluates a ratio between positive and negative producing phases of stance rather than simply the ratio between total positive and negative lower-limb joint work during stance (Sawicki et al., 2009). By calculating a mechanical ratio in this manner, we consider the timing of work produced. The timing of work produced reflects how work relates to the efficiency of movement. When using metabolic cost to evaluate walking efficiency, the timing of positive work is critical to its corresponding effect on forward progression (Galle et al., 2013; Malcolm et al., 2015). Furthermore, this ratio inherently accounts for variation in self-selected walking speed when assuming that the variation in self-selected walking speed has a consistent effect on the magnitudes of joint work during each stance phase (Graf et al., 2005; Schenck and Kesar, 2017).

The purpose of this study was to evaluate the effects of revascularization surgery on walking speed and walking mechanics in patients with PAD. A decrease in positive work during late stance and an increase in negative work during early stance has been reported when artificially restricting plantarflexion movement in healthy adults (Huang et al., 2015). Here, we hypothesized the alternative where revascularization surgery would increase positive work during late stance and decrease negative work during early stance. In addition, we hypothesized that the mechanical ratio at each lower limb joint would increase following revascularization surgery.

Subjects and Methods

Participant Recruitment-

A prior power analysis was conducted for the primary outcome measure of a change in Ankle Brachial Index (ABI). Recruitment and evaluation of thirty-five patients was calculated to provide a power of 99% using pilot data for change in ABI. Fifty patients with PAD were enrolled and completed a baseline study visit. Fifteen patients did not attend the study visit following revascularization surgery corresponding to an attrition of 30%. Thirty-five patients with PAD (age: 62.3±5.75 yrs, mass: 85.7±16.1 kg, height: 176.0±7.7 cm, BMI: 27.6±4.3 kgm⁻², Table 1) were recruited from the Omaha Veterans Affairs Medical Center and 35 healthy adults (age: 65.1±8.9 yrs, mass: 81.8±14.2 kg, height: 173.0±6.5 cm, BMI: 27.3±4.3 kgm⁻²) were recruited from the surrounding community. There were no significant differences for age, weight, or height between patients with PAD and healthy adults (p > 0.05). This study was approved by the University of Nebraska Medical Center and the Omaha Veterans Affairs Medical Center Institutional Review Boards. Subjects were enrolled in the study upon providing written informed consent. Researchers were not blinded to whether the subject had PAD or was a healthy control during data collections or during post processing of data. The subject could not be blinded to their condition. Control subjects were eligible for recruitment if they had normal pulses, normal ABI at rest and after stress, and no evidence of claudication or other walking impairment in a walking test. Patients with PAD were eligible for recruitment if they had 1) a positive history of chronic claudication, 2) exercise limiting claudication established by history and direct observation during a screening walking test administered by the evaluating vascular surgeon, 3) documented lower extremity occlusive disease based on resting ankle-brachial index measurement and arterial imaging, 4) stable blood pressure, regimen, stable lipid regimen, stable diabetes regimen and risk factor control for 6 weeks. The exclusion criteria were: 1) rest pain or tissue loss due to PAD (Fontaine stage III and IV), 2) acute lower extremity ischemic event secondary to thromboembolic disease or acute trauma and 3) walking capacity significantly limited by conditions other than claudication including leg (joint/musculoskeletal, neurologic) and systemic (heart, lung disease) pathology. Revascularization surgery took the form of open bypass or endovascular intervention in the aortoiliac or femoropopliteal arterial segments.

Table 1. Baseline characteristics.

Continuous data are presented as means ± standard deviation. All other values are number of patients in each group and subgroup. The subset of patients with PAD represents patients with net work across all phases of stance and lower-limb joints that decreased at least 30% more than the majority of patients from baseline to six months following surgery.

Characteristics	Patient total	Patient Majority	Patient Subset
No. in group	35	27	8
Age, y	62.3 ± 5.75	63.48 ± 5.93	58.88 ± 3.44
Height, cm	176.0 ± 7.7	176.68 ± 7.37	173.49 ± 9.22
Weight, kg	85.7 ± 16.1	85.92 ± 15.80	85.46 ± 19.21
Hypertension	27	21	6
Diabetes mellitus	13	11	2
Dyslipidemia	27	22	5
Past smoker	13	10	3
Current smoker	22	17	5
Obesity	10	7	3
Coronary Artery Disease	8	7	1
Family History	10	8	2
Endovascular Revascularization	14	13	1
Bypass Revascularization	21	14	7
Surgery location
Aortoiliac	12	8	4
Femoropopliteal	9	6	3
Aortoiliac and femoropopliteal	14	13	1

Study Protocol-

For patients with PAD, we conducted motion capture measurements during a visit prior to and six months following revascularization surgery (Figure 1). Healthy participants conducted the same protocol for only a single visit. Retroreflective markers were placed at anatomical locations using a modified Helen-Hayes marker system (McCamley et al., 2017). Each visit consisted of five-meter over-ground walks across eight in-ground force plates (AMTI, Watertown, MA) until at least six quality foot-to-force plate contacts were recorded for each leg. A quality foot-to-force plate contact was considered to be a single step onto a force plate without the foot crossing the plate’s edges. During each walk, three-dimensional kinematics were calculated from motion capture recordings using 17 high-speed Raptor cameras and Cortex 6.1 software (Motion Analysis Corp, Santa Rosa, CA). Following each individual walking trial, a mandatory seated rest period of one minute was implemented to avoid the development of ischemic pain during the walking trials.

Figure 1.

Flowchart of enrollment and study design.

Measurements-

Walking speed and joint mechanics were considered in both study groups. Walking speed was calculated as the average distance traveled per step per second as measured from the retroreflective marker placed on the heel over an integer number of strides. The first and last step of each trial were excluded resulting in approximately 35 steps per participant over all the walking trials. Visual3D (C-Motion, Inc., MD) was used to calculate sagittal plane ankle, knee, and hip joint powers during stance. Stance was divided into three phases: early (1–28%), middle (29–74%), and late (75–100%) (Huang et al., 2015). The integral of each joint power was calculated for each phase of stance using a custom script in MATLAB 2019b (Mathworks Inc., Natick, MA). Ankle, knee, and hip joint work were summed for each phase to determine the net lower limb joint work. For each joint’s mechanical ratio, positive-producing phases of stance were divided by negative-producing phases of stance.

$$Anklemechanicalratio=\left|\frac{Latestancework}{Early+Middlestancework}\right|$$ (1)

$$Kneemechanicalratio=\left|\frac{Middlestancework}{Early+Latestancework}\right|$$ (2)

$$Hipmechanicalratio=\left|\frac{Early+Latestancework}{Middlestancework}\right|$$ (3)

For the ankle joint, the integral of joint power across late stance is a positive value, whereas the integrals of joint power across early and middle stance are negative values in healthy participants. To evaluate the ankle joint’s mechanical ratio, we found the ratio of late stance work versus the sum of early and middle stance work (Eq 1). This quantifies work performed across stance as a multiple of energy expended for accelerating joint rotations versus energy expended for the slowing of joint rotations. A mechanical ratio of one is interpreted as equal amounts of positive and negative work performed at the joint across stance. For the knee joint, the mechanical ratio is considered middle stance work divided by the sum of early and late stance work (Eq 2). For the hip joint, the mechanical ratio is considered the sum of early and late stance work divided by middle stance work (Eq 3).

Statistical Analysis

We performed statistical analyses on the effects of revascularization on walking speed and joint mechanics using RStudio (RStudio, Inc., Boston, MA). Data collections and the initial processing of data was the same for all individuals and sessions. A student’s t-test was used to assess changes in self-selected walking speed as a result of revascularization. A linear mixed-effects model consisting of two fixed effects, walking speed and net lower limb joint work, and a random effect for within-subject was used to assess significant effects of revascularization surgery on net lower limb joint work for each phase of stance. A general linear model was used to assess differences in net lower limb joint work for each stance phase between patients at baseline and healthy adults. A general linear model was used to assess differences in net lower limb joint work for each stance phase between patients six months following surgery and healthy adults. Net lower limb joint work was evaluated using an α-level of 0.05 that was corrected using the Bonferroni method for 9 statistical assessments. Wilcoxon signed rank tests for with and without paired comparisons were used to evaluate statistical significance of mechanical ratios. Mechanical ratios were evaluated using an α-level of 0.05 that was corrected using the Bonferroni method for 12 statistical assessments.

Within the hip joint’s mechanical ratio, there was an observable dichotomy among patients. A large decrease in hip joint mechanical ratio was found in a subset of patients. Other groups have evaluated their patient data following an intervention by separating “responders” and “nonresponders” in a variety of patient populations with complicated medical history (Aaron et al., 2017; Bowden et al., 2013; Carne et al., 2005; Prouskas et al., 2022; Reisman et al., 2013; Whipple et al., 2021). We considered comorbidities and age as potential confounding factors, but these characteristics were not sufficient to separate the subset of patients with the large decrease in hip joint’s mechanical ratio from the majority. We continue to use group names of subset and majority due to a group name of “nonresponder” seeming inappropriate when it is in reference to a group that received a surgical intervention. Therefore, the majority of patients with PAD (n = 27) and a subset of patients (n=8) were separated and defined by a gap of 30% in the change in net work across all of stance and lower limb joints prior to and following revascularization. These groups were confirmed to be significantly different using a student’s t-test (p<0.001). We considered the ankle and knee mechanical ratio without the subset of participants but excluding the subset of participants did not change significant effects. As a consequence, ankle and knee mechanical ratio are reported without subdividing groups.

Results

Self-selected walking speed significantly increased from 1.13 ± 0.20 ms⁻¹ to 1.26 ± 0.18 ms⁻¹ in patients following revascularization (p<0.001). Revascularization surgery also resulted in increased net negative joint work performed during early stance (p<0.001, Table 2) and decreased net positive joint work during late stance (p<0.001). There were no significant differences in middle stance work associated with revascularization surgery (Figure 2). Negative work performed during early stance increased to similar values as healthy adults following surgery (p=0.864). In contrast, positive work performed during late stance became significantly lower compared to healthy adults following surgery (p=0.003).

Table 2. Net Lower Limb Joint Work.

Between-group comparisons were evaluated using a general linear model and are identified as Baseline vs Healthy adults and Post-surgery vs Healthy adults. Repeated effects were assessed using linear mixed model and are identified as Baseline vs Post-surgery.

Early Stance Work	Standard Error	t-value	p-value
Baseline vs. Healthy adults	0.003	5.794	<0.001*
Post-surgery vs. Healthy adults	0.004	0.172	0.864
Baseline vs. Post-surgery	0.003	5.843	<0.001*
Middle Stance Work
Baseline vs. Healthy adults	0.003	8.084	<0.001*
Post-surgery vs. Healthy adults	0.007	4.901	<0.001*
Baseline vs. Post-surgery	0.007	1.001	0.156
Late Stance Work
Baseline vs. Healthy adults	0.005	1.522	0.133
Post-surgery vs. Healthy adults	0.006	3.038	0.003*
Baseline vs. Post-surgery	0.002	5.328	<0.001*

^*indicate statistical significance of effect or between-group difference evaluated at an alpha level of 0.006.

Figure 2.

Mean and standard deviation of net lower limb joint work performed by patients with peripheral artery disease (PAD) before and six months following revascularization surgery as well as healthy participants. Stars indicate statistical significance with a p-value less than 0.006. All statistical effects were evaluated including self-selected walking speed as a covariate. Patients had a significant increase in negative work during early stance and decrease in positive work during late stance. * indicate statistical significance.

Revascularization surgery resulted in a small but significant decrease in the ankle joint’s mechanical ratio (Figure 3). Patients continued to have a lower ankle mechanical ratio compared to their healthy counterparts (p<0.001). Conversely, the knee joint mechanical ratio was more similar to healthy adults following revascularization (Table 3).The majority of patients with PAD had a significant increase in hip joint ratio (p<0.001) whereas the subset of patients had a decrease in hip joint mechanical ratio following revascularization (p=0.004). The majority of patients significantly increased in hip mechanical ratio compared to healthy adults following revascularization surgery (p<0.001).

Figure 3:

Joint mechanical ratios for the ankle (A), knee (B), and hip (C) for patients at baseline and post-surgery as well as a control group of healthy, older adults. A subset of patient participants experienced at least a 30% greater decrease from baseline to post-surgery in hip joint efficiency compared to the majority of patients. Dashed lines indicate the same patient’s baseline and post-surgery mechanical ratio. * indicate statistical significance.

Table 3. Mechanical Ratio of Each Lower-Limb Joint.

Wilcoxon signed ranked tests were used to evaluate significant effects.

Ankle Mechanical Ratio	W-value or V-value	p-value
Baseline vs. Healthy adults	1225	<0.001*
Post-surgery vs. Healthy adults	1225	<0.001*
Baseline vs. Post-surgery	604	<0.001*
Knee Mechanical Ratio
Baseline vs. Healthy adults	865	0.003*
Post-surgery vs. Healthy adults	720	0.210
Baseline vs. Post-surgery	163	0.012
Hip Mechanical Ratio
Baseline vs. Healthy adults	627	0.012
Post-surgery vs. Healthy adults	767	<0.001*
Baseline vs. Post-surgery	5	<0.001*
Subset Low Hip Mechanical Ratio
Baseline vs. Healthy adults	233	0.027
Post-surgery vs. Healthy adults	17	<0.001*
Baseline vs. Post-surgery	45	0.004*

^*indicate statistical significance of effect or between-group difference evaluated at an alpha level of 0.004.

Discussion

The purpose of this study was to evaluate the effects of revascularization surgery on walking mechanics in patients with PAD. We hypothesized that the improved blood flow to the plantar flexor muscles from revascularization surgery would increase positive work during late stance and a decrease in negative work during early stance. Counter to our hypothesis, negative work during early stance increased and positive work during late stance decreased. Despite patients’ significant increase in self-selected walking speed, these analyses suggest inefficient joint mechanics. The increase in self-selected walking speed is considered a beneficial walking improvement, but it did not support the observed changes in joint work (Chen et al., 2017; Machado et al., 2020). Instead, patients at baseline had less negative work during early stance, more negative work during middle stance, and similar amounts of positive work during late stance compared to healthy adults. Following surgery, patients produced more negative work during early stance and less positive work during late stance compared to healthy adults. These findings suggest that patients’ walking mechanics became less efficient despite the positive effect of an increase in self-selected walking speed. The amelioration of claudication pain allowed patients to walk faster but this did not also translate into a more efficient walking strategy in terms of mechanics.

By analyzing joint-level mechanical ratio, we identified that patients’ ankle joints had a reduced mechanical ratio six months following revascularization which continued to be substantially lower than their healthy counterparts. Conversely, the hip joint’s mechanical ratio improved. Therefore, it is possible that improvements at the hip may support the observed improvements in self-selected walking speed. However, an evident dichotomy complicated hip mechanical ratio results among patients. During statistical analyses, a subset of patients was observed to have a much lower hip joint mechanical ratio which warranted analysis as a separate subset. The subset of patients produced positive work at the hip in a less effective manner than the majority of patients represented by a decrease in mechanical ratio. The subset also had lower ankle mechanical ratio compared to the majority of patients at baseline and following revascularization. A decrease in mechanical ratio represents either an increase in negative work, a decrease in positive work, or a less effective timing of producing positive work. Therefore, the decrease in hip mechanical ratio in addition to a lower ankle mechanical ratio suggests that the subset of patients had a less effective gait strategy prior to surgery that may have worsened following surgery. These changes may be due to a relationship with disease characteristics or the patients’ health status; however, this was not observable through evaluation of comorbidities.

The majority of patients’ hip mechanical ratio improved from baseline to six months following revascularization surgery. From our data, this offers rationale for the observed increase in self-selected walking speed. The dependency of the muscles about the hip for forward progression is representative of a natural shift from distal-to-proximal muscle groups as a result of aging (Browne and Franz, 2018; Kulmala et al., 2014). However, patients with PAD following revascularization had hip mechanical ratios that were significantly larger than the older, healthy participants. These findings may correspond to an exaggerated effect similar to that of aging where reductions to ankle work at late stance results in a greater dependency on the hip for forward propulsion during walking (Franz, 2016).

Revascularization surgery improved self-selected walking speed, but revascularization alone did not improve walking mechanics in patients with PAD. The importance of revascularization surgery for these patients cannot be understated and should not be diminished by these results (Devine et al., 2016; Kinlay, 2016; Vartanian and Conte, 2015). While our study did not include exercise rehabilitation for patients, our study supports a potential need for additional treatment following revascularization. Such treatment may be in the form of standard postoperative rehabilitative exercise therapy or may include therapies that focus on the well-described ischemic myopathy that is present in the legs of patients with PAD (Koutakis et al., 2015; Makris et al., 2007; Park et al., 2022). The work on the myopathy of PAD suggests that revascularization alone may not be sufficient to improve the muscle and tissue damage sustained from years of continual and degenerative leg ischemia within six months. Previous literature reported that revascularization operations followed by supervised exercise therapy led to greater improvements in maximum walk distance compared to surgery alone (Badger et al., 2007; Fakhry et al., 2015; Jakubsevičienė et al., 2014; Lundgren et al., 1989). Future research into supplemental rehabilitative therapies, medications that address the mechanisms operating in the myopathy of PAD, or assistive devices may improve patient outcomes following surgery (Bashir et al., 2021; Dinkel et al., 2022; Fickey et al., 2018; Gerhard-Herman et al., 2017; Park et al., 2020).

The primary limitation of this study was the lack of a six-month session for healthy participants. This limited our statistical analyses by not providing a controlled measure of group variance over time. Furthermore, there are difficulties associated with longitudinal, clinical studies that inevitably increase the variability of the study data between collections.

Conclusion

This study tested the hypothesis that revascularization would improve walking mechanics in patients with PAD. We evaluated net lower limb joint work during early, middle, and late stance in patients before and after revascularization. Counter to our hypothesis, patients’ walking mechanics did not improve following revascularization surgery. However, the patients’ self-selected walking speed did improve significantly following revascularization. Furthermore, we analyzed the mechanical ratio of each joint to evaluate the joint-level effects of surgery. Ankle mechanical ratio was reduced while there was a significant increase in the hip mechanical ratio. These findings suggest that revascularization surgery should be supported with additional therapies that facilitate the restoration of muscle, tissue, and nervous system damage caused by years of having reduced blood flow to the limbs.

Table 4. Mean Mechanical ratio of Groups.

Mean mechanical ratio is reported with standard deviation in parentheses. A subset of patients with PAD represents patients with net work across all phases of stance and lower-limb joints that decreased at least 30% more than the majority of patients from baseline to six months following surgery.

Group	Ankle	Knee	Hip	Hip Subset
Baseline	1.053 (0.135)	0.262 (0.037)	0.403 (0.068)	0.546 (0.287)
Post-surgery	1.006 (0.157)	0.275 (0.042)	0.471 (0.091)	0.097 (0.041)
Healthy adults	1.880 (0.248)	0.289 (0.037)	0.340 (0.112)	N/A