Systematic review. As outlined in Figure 1, electronic searches yielded 1325 results from MEDLINE (395), CINAHL (110), EMBASE (661), and Scopus (159), of which 330 were duplicates and 995 potentially relevant citations. Of these, 972 citations were excluded through a paired consensus process, leaving a total of 23 citations for which full articles were retrieved. An additional 9 full articles were identified by reviewing secondary sources. Of the 32 full articles retrieved, 14 met the inclusion criteria (Table 4A, 4B, 4C, 4D, 4E)4,12,21-32: 10 from primary sources and 4 from secondary sources. Eighteen (18) studies were excluded for the following reasons: no intervention (7), nonexercise-based intervention (4), no calf muscle or ankle ROM exercises (1), review article (1), industry report (1), incorrect patient population (3), or not available through the Western University Library (authors’ facility) (1).
Population. The 519 participants in all of the included studies (14) were community-dwelling individuals who walked independently. Minimal adverse events were reported in the included studies. The majority of studies (9) included participants with both CVI and VLUs. Three (3) studies included patients with no open wounds,4,21,23 and 1 study included persons with post thrombotic syndrome.27 The age range for study participants was 27 to 91 years. All but 2 studies22,32 included both men and women in the data collection. Eight (8) studies had participants lost to follow-up for various reasons.21-25,27,28,30 Wound duration for the studies that included open ulcers varied; 1 study included a wound that was present for 51 years.24 The study participants were recruited while receiving standard wound care either through a regional home care program or outpatient wound clinic for active or recently healed VLUs. One (1) of the studies required participants to have full ankle ROM to be included.12
Study types. Eight (8) studies were randomized controlled trials (RCTs),22,25-31 1 was a prospective nonrandomized study,12 1 used a “randomized matched pairs” design,21 and 4 were prospective single-arm studies.4,23,24,32 Control groups consisted of no treatment,21 education only,29 usual care and compression,12,25,28,31 and compression only.22 Three (3) of the studies included exercise as concurrent treatment in the control group with the addition of more intensive, supervised exercises as part of the intervention exercise program.26-28
Leg compression was used at all times in 9 studies12,22,23,25,26,28-31 and during exercise only in 1 study.21 Compression was not used during exercise in 2 studies,4,24 recommended as optional or at the discretion of the health care provider in 1 study,27 and not at all in 1 study.32 The types of compression identified included compression stockings (108 study participants),21,22,23,27 compression bandaging (104 study participants12,26,29,30) either (184 study participants),28 or not described (82 study participants).25,31
Intervention. Exercise programs in the treatment groups included calf muscle strengthening programs,4,12,25 calf muscle strengthening and ankle stretching ROM programs22-25,27,28,30,32, walking programs,28,29 and 1 unspecified.21 Of the 14 studies assessed, 13 discussed some form of supervision and education for the exercise intervention group; 5 noted the supervision and education for the exercise intervention were given by a health care provider with expertise in exercise prescription, such as a physiotherapist or exercise physiologist.22-24,28,30 The duration of the exercise program also varied among the studies: exercise intervention ranged from 2 times per week to daily, 5-10 minutes to 1 hour per session, and varied between 7 days and 18 months.
Outcomes. Seven (7) studies (159 participants) measured calf hemodynamics using APG.4,12,21-23,25,30 CMP function was measured using venous hemodynamic values through APG.13,16-18,33 Participants in all 7 had an improvement in CMP function after exercise. Six (6) of the 7 studies reported a greater increase in EF and decrease in RVF for the treatment group in comparison to the control group. The seventh study21 did not measure EF or RVF but also noted an improvement in CMP hemodynamics, with a 16% decrease in mean venous capacity in the treatment group, which was greater than the control group that did not show any change.
Changes in ankle ROM were measured in 6 studies (137 participants).22,24,26,27,30,32 All but 1 of the studies found an increase in ankle ROM in favor of the exercise intervention group.22 However, ankle ROM measurements were performed using different assessment tools including an inclinometer,27 a goniometer,26,27,30,32 and a biodex machine.22 Positioning during ankle ROM measurements was inconsistent: 3 studies assessed participants with their knees bent,22,27,30 2 with the participant’s knee straight,26,32 and 1 was unspecified.24 One (1) study evaluated the effects of exercise on ROM of left and right ankles separately and then utilized the more conservative measurement for data analysis.32
Calf muscle strength was assessed in 4 studies (114 participants).4,12,22,27 All of the included studies demonstrated an increase in calf muscle strength and/or endurance in the treatment group compared to the control group. Strength measurements were completed using different measurement tools, including a biodex machine,4,22 percentage of max plantar flexion with an ergometer,12 and the heel lift test.27
Five (5) studies (317 participants) assessed the effects of calf muscle exercise on wound healing.25,28,29,30,31 Four (4) demonstrated improved healing rates in the treatment group compared to the control group,28-31 and for the study where healing rates showed no improvement the author stated the results may be due to the small study sample and that the study was not powered to show an effect on ulcer healing, allowing high risk for type II error.25 The 2013 RCT (N = 40) by Ahmed et al31 showed a significant decrease in the Pressure Ulcer Scale for Healing (PUSH tool) score and reduction of the surface area in the treatment group versus control after 12 days. In the 2012 RCT by Heinen et al (N = 184),28 patients with leg wounds occurring after initiating an exercise trial had significantly fewer wound months than patients who had wounds present at baseline in both the control and treatment groups. These findings suggest a potentially positive impact of exercise intervention on healing times.
Methodological quality of the controlled studies. Four (4) studies did not have PEDro appraisal because they were prospective, single-arm studies.4,23,24,32 The remaining 10 studies scored between 4 and 7 out of 10 on the PEDro scale (see Table 3). The mean PEDro score was 5.8, indicating low overall methodological quality.19 Authors of all 10 studies conducted between-group statistical comparisons and reported both average values and measures of variability for at least 1 key outcome. None of the studies was able to meet the criteria of blinding of all therapists or of all assessors due to the nature of the intervention. All of the studies except Kan and Delis12 had participants that were randomly assigned to groups.
Meta-analysis results. The present meta-analysis evaluated the evidence in the literature related to the effects of exercise intervention on the CMP in participants with CVI with or without VLUs. Although 14 articles met the inclusion criteria for review, only 8 were included for meta-analysis due to the variability of the study methodology and data available to calculate effect sizes.22,25-31 Of the 7 studies that reported calf hemodynamics,4,12,21-23,25,30 3 were included in a meta-analysis to calculate the effect of exercise on CMP function (83 participants), specifically for the values of EF and RVF.22, 25, 30 The results from the meta-analysis for EF showed a significant increase in favor of the treatment group with a large effect size (Hedge’s g = 0.83; 95% CI 0.35-1.30, P <.001) (see Figure 2). RVF also favored the intervention group although it was not statistically significant (Hedge’s g = 0.42; 95% CI -0.03-0.862, P = .066) (see Figure 3).
Eight (8) studies4,12,22,24,26,27,30,32 evaluated the effects of exercise intervention on ROM and/or ankle strength, both of which affect the efficiency of the CMP. Due to the heterogeneity of the outcomes used to assess CMP strength, none of the studies was included in meta-analysis. Four (4) RCTs (116 participants) assessing ankle ROM were similar and facilitated combining results.22,26,27,30 The results from the meta-analysis for ankle ROM showed a moderate effect size toward increased ROM in the treatment group compared to control group, but it was not statistically significant (Hedge’s g = 0.62; 95% CI -0.15-1.39, P = .116) (see Figure 4).
Included in this review are 5 studies assessing the effect of exercise on wound healing.25,28,29,30,31 Three (3) measured whether wounds were healed or not healed after 12 weeks and were combined in a meta-analysis to calculate the effect of exercise on VLU healing (N = 93).25,29,30 Results showed no significant difference in healing rates between exercise groups and control groups after 12 weeks of CMP exercises (RR: 1.027; 95% CI 0.77 to 1.38, P = .860) (see Figure 5).