Peripheral Vascular Rehabilitation Programs

Number: 0458

Policy

Aetna considers medical supervision of peripheral vascular rehabilitation programs medically necessary for the treatment of persons with symptomatic peripheral artery disease (PAD) (i.e., intermittent claudication).

Program Description

Up to 36 sessions over a 12-week period are considered medically necessary if all of the following components of a supervised exercise therapy (SET) program are met:

  • consist of sessions lasting 30-60 minutes comprising a therapeutic exercise-training program for PAD in members with claudication; and
  • be conducted in a hospital outpatient setting, or a physician’s office; and
  • be delivered by qualified auxiliary personnel to ensure benefits exceed harms, and who are trained in exercise therapy for PAD; and
  • be under the direct supervision of a physician, physician assistant, or nurse practitioner/clinical nurse specialist trained in both basic and advanced life support techniques; and
  • Member must have a face-to-face visit with the physician responsible for PAD treatment to obtain the referral for SET program. At this visit, the member must receive information regarding cardiovascular disease and PAD risk factor reduction, which could include education, counseling, behavioral interventions, and outcome assessments.

Aetna considers medical supervision of peripheral vascular rehabilitation programs experimental and investigational for persons with absolute contraindications to exercise and for all other indications because the value of such supervision for other indications is not well documented by the available peer-reviewed published medical literature.

Aetna considers the PADnet System and testing program experimental and investigational for evaluation of peripheral artery disease and other indications because of insufficient evidence of its effectiveness.

Aetna considers the QuantaFlo System experimental and investigational for screening of peripheral artery disease because the effectiveness of this approach has not been established. Note: Measurement of ankle brachial index is considered integral to the evaluation and management service and is not separately reimbursed.

Aetna considers transcutaneous visible light hyperspectral imaging (HyperView) experimental and investigational for determination of oxygenation levels in superficial tissues for individuals with potential circulatory compromise (e.g., peripheral vascular disease) and all other indications because of insufficient evidence of its effectiveness.

Background

Both physical activity and medications are used to treat peripheral vascular disease.  Vascular specialists agree that long daily walks are the best treatment for people with intermittent claudication, thereby increasing the distance of pain-free walking through the development of collateral circulation.

Patients whose legs hurt during physical activity often find it hard to follow a walking program.  For this reason, the cardiac rehabilitation departments of some hospitals have created supervised exercise programs that offer support and encouragement.  These peripheral vascular rehabilitation programs are geared to patients with various peripheral vascular disorders, including post-surgical patients (e.g., peripheral angioplasty, peripheral arterial bypass, stent) and patients with peripheral arterial disease who are not candidates for surgery.  Services are provided by a multi-disciplinary team, which includes nurses, physical therapists and physicians.  The usual duration of the program is 3 times a week for 12 weeks (36 visits).  The goal of treatment is to improve endurance and decrease symptoms.

There has been insufficient evidence in the medical literature demonstrating superior outcomes of such supervised exercise programs over exercise without supervision.

The American College of Cardiology/American Heart Association's 2005 practice guidelines for the management of patients with peripheral arterial disease (Hirsch et al, 2006) recommended a program of supervised exercise training (treadmill or track walking, a minimum of 30 to 45 mins, in sessions performed at least 3 times per week for a minimum of 12 weeks) as an initial treatment modality for patients with intermittent claudication.

On the other hand, McDermott et al (2006) reported that among patients with peripheral arterial disease, self-directed walking exercise performed at least 3 times weekly is associated with significantly less functional decline during the subsequent year.  Similar trends were also seen in the subset of asymptomatic patients with peripheral arterial disease.  In addition, Fabbian et al (2006) stated that a rehabilitation program performed at home at a specific velocity, just below the pain threshold speed appeared to be well-suited for hemodialysis patients with peripheral arterial disease because it induced functional improvements and vascular adaptations with low costs.

Furthermore, a Cochrane systematic evidence review (Bendermacher et al, 2006) found that supervised exercise therapy has not been proven to be better than non-supervised exercise therapy in managing patients with intermittent claudication.  The Cochrane review compared the effects of supervised versus non-supervised exercise therapy on the maximal walking time or distance for individuals with this condition (Bendermacher et al, 2006).  The Cochrane Peripheral Vascular Diseases Group searched their specialized register and the Cochrane Central Register of Controlled Trials (CENTRAL) database in the Cochrane library.  In addition, these investigators hand-searched the reference lists of relevant articles for additional trials.  There was no restriction on language of publication.  Randomized and controlled clinical trials comparing supervised exercise programs with non-supervised exercise programs for people with intermittent claudication were selected.  Two authors independently selected trials and extracted data.  One author assessed trial quality and this was confirmed by a second author.  For all continuous outcomes the authors extracted the number of participants, the mean differences, and the standard deviation.  If data were available, the standardized mean difference was calculated using a fixed-effect model.  These researchers identified 27 trials, of which 19 had to be excluded because the control group received no exercise therapy at all.  The remaining 8 trials involved a total of 319 male and female participants with intermittent claudication.  The follow-up ranged from 12 weeks to 12 months.  In general, the supervised exercise regimens consisted of 3 exercise sessions per week.  All trials used a treadmill walking test as one of the outcome measures.  The overall quality of the included trials was good, though the trials were all small with respect to the number of participants, ranging from 20 to 59.  Supervised exercise therapy showed statistically significant and clinically relevant differences in improvement of maximal treadmill walking distance compared with non-supervised exercise therapy regimens in the short-term, with an overall effect size of 0.58 (95 % confidence interval: 0.31 to 0.85) at 3 months.  This translated to a difference of approximately 150 meters increase in walking distance in favor of the supervised group.  However, there is a high possibility of a training effect as the supervised exercise therapy groups were trained primarily on treadmills (and the home based were not) and the outcome measures were treadmill based.  The authors concluded that supervised exercise therapy is suggested to have clinically relevant benefits compared with non-supervised regimens in the short-term, which is the main prescribed exercise therapy for people with intermittent claudication. However, the clinical relevance has not been demonstrated definitely and will require additional studies with a focus on durability of outcomes and improvements in quality of life (Bendermacher et al, 2006).

In a systematic review of the clinical evidence for home-based versus center-based exercise programs for older adults, Ashworth et al (2005) has observed that home based programs for peripheral vascular disease appear to have a significantly higher long-term adherence rate than supervised center-based programs.  However, this conclusion was based primarily on the one study (with the highest quality rating of the studies found) of sedentary older adults.  This showed an adherence rate of 68 % in the home-based program at 2-year follow-up compared with a 36 % adherence in the center-based group.

Crowther and colleagues (2008) examined the effects of a 12-month exercise program on lower limb mobility (temporal-spatial gait parameters and gait kinematics), walking performance, peak physiological responses, and physical activity levels in individuals with symptoms of intermittent claudication due to peripheral arterial disease (PAD-IC).  Participants (n = 21) with an appropriate history of PAD-IC, ankle-brachial pressure index (ABI) less than 0.9 in at least one leg and a positive Edinburgh claudication questionnaire response were prospectively recruited.  Subjects were randomly allocated to either a control PAD-IC group (CPAD-IC) (n = 11) that received standard medical therapy and a treatment PAD-IC group (TPAD-IC) (n = 10), which also took part in a 12-month supervised exercise program.  A further group of participants (n = 11) free of PAD (ABI greatetr than 0.9) and who were non-regular exercisers were recruited from the community to act as age and mass matched controls.  Lower limb mobility was determined via 2-dimensional video motion analysis.  A graded treadmill test was used to assess walking performance and peak physiological responses to exercise.  Physical activity levels were measured via a 7-day pedometer recording.  Differences between groups were analyzed via repeated measures analysis of variance.  The 12-month supervised exercise program had no significant effect on lower limb mobility, peak physiological responses, or physical activity levels in TPAD-IC compared with CPAD-IC participants.  However, the TPAD-IC participants demonstrated significantly greater walking performance (171 % improvement in pain-free walking time and 120 % improvement in maximal walking time compared with baseline).  The authors concluded that these findings confirmed that a 12-month supervised exercise program will result in improved walking performance, but does not have an impact on lower limb mobility, peak physiological responses, or physical activity levels of PAD-IC patients.

Franz and co-workers (2010) evaluated the effectiveness of a 12-week, institution-based, supervised exercise rehabilitation program with atherogenic risk factor modification in improving cardiovascular profile, ambulatory function, and quality of life of patients with PAD by comparing pre- and post-program measurements.  Participants were prospectively enrolled.  Cardiovascular profile variables, ambulatory function tests, and quality of life questionnaires were evaluated.  Of 101 institution-based program participants, 69 completed the 12-session minimum and 47 completed a post-program evaluation.  Mean post-program results were significantly different from pre-program results, corresponding to improvement, for the following variables: triglyceride levels (p < 0.036), both function tests (p < 0.001 for both), 4 of 5 Walking Impairment Questionnaire measurements, and Intermittent Claudication Questionnaire score (p < 0.001).  The authors concluded that this supervised exercise program improved the cardiovascular profiles, ambulatory function, and quality of life of PAD patients completing the program and is a viable adjunct to drug therapy and surgical intervention.  These initial findings were skewed by the modest completion rate (68 %) and the low post-program evaluation rate (47 %).

In a review on the associations between PAD and ischemic stroke and the implications for primary and secondary prevention, Banerjee and colleagues (2010) concluded that in both primary and secondary prevention settings, PAD indicates a high-risk of future events.  They noted that data on which additional preventive measures are beneficial in this patient group are lacking, but the presence of PAD does have implications for current management in both primary and secondary prevention of stroke.

In a randomized controlled trial, Saxton et al (2011) investigated the effects of upper- and lower-limb aerobic exercise training on disease-specific functional status and generic health-related quality of life (QoL) in patients with IC.  The study recruited 104 patients (mean age of 68 years; range of 50 to 85) from the Sheffield Vascular Institute.  Patients were randomly allocated to groups that received upper-limb (ULG) or lower-limb (LLG) aerobic exercise training, or to a non-exercise control group.  Exercise was performed twice-weekly for 24 weeks at equivalent limb-specific relative exercise intensities.  Main outcome measures were scores on the Walking Impairment Questionnaire (WIQ) for disease-specific functional status, the Medical Outcomes Study Short Form version 2 (SF-36v2), and European Quality of Life Visual Analog Scale (EQ-VAS) for health-related QoL.  Outcomes were assessed at baseline, and at 6, 24, 48, and 72 weeks.  After 6 weeks, improvements in the perceived severity of claudication (p = 0.023) and stair climbing ability (p = 0.011) versus controls were observed in the ULG, and an improvement in the general health domain of the SF-36v2 versus controls was observed in the LLG (p = 0.010).  After 24 weeks, all 4 WIQ domains were improved in the ULG versus controls (p ≤ 0.05), and 3 of the 4 WIQ domains were improved in the LLG (p < 0.05).  After 24 to 72 weeks of follow-up, more consistent changes in generic health-related QoL domains were apparent in the ULG.  The authors concluded that these findings supported the use of alternative, relatively pain-free forms of exercise in the clinical management of patients with IC.

In a comparative longitudinal cohort study, Fakhry et al (2011) evaluated effects of a structured home-based exercise program on functional capacity and QoL in patients (n = 142) with IC after 1-year follow-up, and compared these results with those from a concurrent control group who received supervised exercise training (SET).  Main outcome measures included the maximum (pain-free) walking distance and the ABI (at rest and post-exercise) were measured at baseline and after 6 and 12 months' follow-up.  Additionally, QoL was evaluated using a self-administered questionnaire consisting of the Euroqol-5D (scale 0 to 1), rating scale (scale 0 to 100), SF-36 (scale 0 to 100), and the Vascular QoL Questionnaire (VascuQol; scale 1 to 7).  Comparison of the groups was performed with adjustment for the non-randomized setting using propensity scoring.  Patients with IC started the structured home-based exercise program, of whom 95 (67 %) completed 12 months' follow-up.  The mean relative improvement compared with baseline was statistically significant after 12 months' follow-up for the maximum and pain-free walking distance (342 %, 95 % confidence interval [CI]: 169 to 516; p < 0.01 and 338 %, 95 % CI: 42 to 635; p = 0.03, respectively) and for the ABI post-exercise (mean change of 0.06; 95 % CI: 0.01 to 0.10; p = 0.02).  For the QoL outcomes, the improvement compared with baseline was statistically significant after 12 months for the VascuQol (mean change of 0.42; 95 % CI: 0.20 to 0.65; p < 0.01) and for the SF-36 physical functioning (mean change of 5.17; 95 % CI: 0.77 to 9.56; p = 0.02).  Compared with the structured home-based exercise program, patients in the control group showed significantly better results in the mean relative improvement of maximum and pain-free walking distance and change in the ABI at rest after 12 months' follow-up.  The authors concluded that structured home-based exercise training is effective in improving both functional capacity and QoL in patients with IC and may be considered as a feasible and valuable alternative to SET.

The BioMedix PADnet Lab was approved by the U.S. Food and Drug Administration on October 12, 2004. PADnet (Peripheral Arterial Disease-Internet Ready) system is a non invasive cardiovascular blood flow monitor to gauge the lower extremity arterial system using pulse volume recordings and oscillometric segmental systolic blood pressures to assist in the identification of vascular disease. It uses automated means to obtain Ankle-Brachial Index/Toe-Brachial Index (ABI/TBI) values and Pulse Volume Recording (PVR) waveforms. The device is capable of sending test results instantly via the web to a vascular specialist for interpretation. Ankle-Brachial Index and Pulse Volume Recording values are used to identify the obstructive disease and determine whether medical or surgical treatment is necessary. The device uses a supplied laptop with specifications, hardware and a user interface. The PADnet is intended to be used by healthcare professionals in a hospital or clinic environment. The device is not intended for pediatric or fetal use. It is also not intended for use on or near non intact skin.

In a Cochrane review, Fokkenrood et al (2013) provided an accurate overview of studies evaluating the effects of supervised exercise programs (SETs) versus non-supervised exercise therapy on maximal walking time or distance on a treadmill for people with intermittent claudication.  For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched September 2012) and CENTRAL (2012, Issue 9).  In addition, these investigators hand-searched the reference lists of relevant articles for additional trials.  No restriction was applied to language of publication.  Randomized clinical trials comparing SETs with non-supervised exercise programs (defined as walking advice or a structural home-based exercise program) for people with intermittent claudication were selected for analysis; studies with control groups, which did not receive exercise or walking advice or received usual care (maintained normal physical activity), were excluded.  Two review authors independently selected trials and extracted data; 3 review authors assessed trial quality, and this was confirmed by 2 other review authors.  For all continuous outcomes, these researchers extracted the number of participants, the mean differences, and the standard deviation.  The 36-Item Short Form Health Survey (SF-36) outcomes were extracted to assess quality of life.  Effect sizes were calculated as the difference in treatment normalized with the standard deviation (standardized mean difference) using a fixed-effect model.  A total of 14 studies involving a total of 1,002 male and female participants with PAD were included in this review.  Follow-up ranged from 6 weeks to 12 months.  In general, supervised exercise regimens consisted of 3 exercise sessions per week.  All trials used a treadmill walking test as one of the outcome measures.  The overall quality of the included trials was moderate to good, although some trials were small with respect to the number of participants, ranging from 20 to 304.  Supervised exercise therapy showed statistically significant improvement in maximal treadmill walking distance compared with non-supervised exercise therapy regimens, with an overall effect size of 0.69 (95 % CI: 0.51 to 0.86) and 0.48 (95 % CI: 0.32 to 0.64) at 3 and 6 months, respectively.  This translated to an increase in walking distance of approximately 180 meters that favored the supervised group.  Supervised exercise therapy was still beneficial for maximal and pain-free walking distances at 12 months, but it did not have a significant effect on quality of life parameters.  The authors concluded that SET has statistically significant benefit on treadmill walking distance (maximal and pain-free) compared with non-supervised regimens.  Moreover, they stated that the clinical relevance of this has not been demonstrated definitively; additional studies are needed that focus on quality of life or other disease-specific functional outcomes, such as walking behavior, patient satisfaction, costs, and long-term follow-up.  

In a meta-analysis, Li and colleagues (2015) examined the effect of structured home-based exercise (SHE) programs on maximal walking time (MWT), pain-free walking time (PFWT), and self-reported walking ability in patients with PAD. These investigators searched the databases including MEDLINE, EMBASE, ISI Web of Knowledge, and the Cochrane Library from inception to December 2013 for randomized controlled trials (RCTs) that assessed the effect of SHE programs on walking ability in patients with PAD.  Meta-analysis was performed based on the searched results.  Moreover, these researchers made a systemic review regarding the results along with their knowledge.  Of all the 348 publications retrieved from the databases, 5 RCTs covering 547 patients reached the inclusion criteria and were involved in the present study.  Both inverse-variance fixed-effects and random-effects model were used to perform meta-analysis. SHE programs improved MWT by mean difference of 66.78 sec (95% confidence interval [CI], 5.15-128.41; P = 0.03), heterogeneity across studies was significant.  When the trial accounting for significant heterogeneity was omitted, SHE programs improved MWT by mean difference of 91.21 sec (95 % CI: 51.96 to 130.45; p < 0.0001).  In contrast, there was no significant heterogeneity across the studies with regard to PFWT and Walking Impairment Questionnaire (WIQ) score; SHE programs improved both PFWT and WIQ scores (mean difference of PFWT, 57.76s; 95 % CI: 20.42 to 95.10; p = 0.002; mean difference of WIQ distance score, 8.67; 95 % CI: 3.86 to 13.49; p = 0.0004; mean difference of WIQ speed score, 8.05, 95 % CI: 4.46 to 11.64; p < 0.0001; mean difference of WIQ stair-climbing score, 6.44; 95 % CI: 2.55 to 10.34; p = 0.001).  The authors concluded that SHE programs improved walking ability in patients with PAD.

In a review on PAD, Kullo and Rooke (2016) stated that supervised exercise for PAD is not reimbursed by insurers in the United States. A home-based, group-mediated, cognitive behavioral walking intervention that included goal setting, self-monitoring, managing pain during exercise, and walking at least 5 days per week lengthened the 6-minute walk distance by 53 m over the distance walked by the control group that received health education alone.

Lawall and colleagues (2017) stated that the prevalence of PAD is increasing worldwide and is strongly age-related, affecting about 20 % of Germans over 70 years of age.  Recent advances in endovascular and surgical techniques as well as clinical study results on comparative treatment methods strengthened the need for a comprehensive review of the published evidence for diagnosis, management, and prevention of PAD.  The inter-disciplinary guideline exclusively covers distal aorta and atherosclerotic lower extremity artery disease.  A systematic literature review and formal consensus finding process, including delegated members of 22 medical societies and 2 patient self-support organizations were conducted and supervised by the Association of Scientific Medical Societies in Germany, AWMF; 3 levels of recommendation were defined, A = "is recommended/indicated", B = "should be considered", and C = "may be considered", means agreement of expert opinions due to lack of evidence.  A total of 294 articles, including 34 systematic reviews and 98 RCTs have been analyzed.  The key diagnostic tools and treatment basics have been defined.  In patients with intermittent claudication endovascular and/or surgical techniques are therapeutic options depending on appropriate individual morphology and patient preference.  In critical limb ischemia, re-vascularization without delay by means of the most appropriate technique is key.  If possible and reasonable, endovascular procedures should be applied first.  The TASC classification is no longer recommended as the base of therapeutic decision process due to advances in endovascular techniques and new crural therapeutic options.  The authors stated that limited new data on rehabilitation and follow-up therapies have been integrated.  They summarized major new aspects of PAD treatment from the updated German Guidelines for Diagnosis and Treatment of PAD; and noted that limited scientific evidence still calls for randomized clinical trials to close the present gap of evidence.

On May 25, 2017, the Centers for Medicare and Medicaid Services (CMS) published a national coverage determination (NCD) for supervised exercise therapy (SET) for symptomatic peripheral artery disease (PAD), with implementation date of July 7, 2018. CMS reviewed the technology assessment of SET. In addition to the evidence submitted by the American Heart Association, CMS reviewed PubMed publications from January 1995 to October 2016. Decision determination was based on review of the evidence in published medical literature from pertinent clinical trials of SET.

The CMS review included an AHRQ sponsored study that included a systematic review which assessed the comparative effectiveness of antiplatelet therapy, medical therapy, exercise, and endovascular and surgical revascularization in PAD patients with intermittent claudication (IC) or critical limb ischemia (CLI). Thirty-five studies (27 RCTs, 8 observational) evaluated the comparative effectiveness of cilostazol, pentoxifylline, exercise therapy, endovascular revascularization, or surgical revascularization in IC patients, with the majority of the studies comparing one intervention with either placebo or one other intervention. The authors found that exercise training improved maximal walking distance (16 RCTs), and exercise training and endovascular intervention improved initial claudication distance (12 RCTs) compared with usual care. Quality-of-life scores (10 RCTs) showed a significant improvement from cilostazol, exercise training, endovascular intervention, and surgical intervention compared with usual care. The authors concluded that for IC patients, exercise therapy, cilostazol, and endovascular intervention all had an effect on improving functional status and QoL; however, the impact of these therapies on cardiovascular events and mortality is uncertain (Jones et al, 2013).

Findings of the Jones et al, 2013 report included (Source: CMS, 2017):

  • SET and the combination of endovascular revascularization + exercise training resulted in large improvements in maximal walking time (MWD) in adults with IC (when compared with usual care). The average age of participants for studies of SET versus usual care was 63 years to 76 years. Strength of Evidence: Moderate.
  • A network meta-analysis found no individual treatment (exercise training, cilostazol, endovascular intervention) to have a statistically significant effect when compared to others for adults with IC with MWD or ACD as an outcome.
  • Exercise training was found to have moderate to large effects on initial claudication distance and pain free walking time (ICD/PFWD). Strength of Evidence: Low.
  • A network meta-analysis found no individual treatment (cilostazol, exercise training, endovascular intervention) to have statistically significant effect when compared to others for adults with IC with ICD/PFWD as an outcome.
  • Exercise training was found to have moderate to large effects on QoL when compared with usual care. Strength of Evidence: Low
  • A network meta-analysis found no individual treatment (cilostazol, exercise training, endovascular, surgical) to have statistically significant effect when compared to others for adults with IC with QoL as the outcome.
  • Inconclusive evidence for exercise training (and cilostazol and ER) in IC for nonfatal MI, nonfatal stroke, amputation, and general safety. Strength of Evidence: Insufficient.
  • There were no studies for exercise training (and cilostazol and ER) in IC for composite cardiovascular events, wound healing, pain, and safety in subgroups. Strength of Evidence: Insufficient.

Murphy et al. (2015) described the results of the CLEVER study at 18 months. The CLEVER study was a randomized, multicenter clinical trial conducted at 29 centers in the United States and Canada. The goal of this study was to report the 18-month efficacy of supervised exercise compared with stenting and optimal medical care. Of 111 patients (mean age 64 yrs) with aortoiliac PAD randomly assigned to receive optimal medical care (OMC), OMC plus supervised exercise (SE), or OMC plus stent revascularization (ST), 79 completed the 18-month clinical and treadmill follow-up assessment. SE consisted of 6 months of supervised exercise and an additional year of telephone-based exercise counseling. Primary clinical outcomes included objective treadmill-based walking performance and subjective quality of life. Peak walking time improved from baseline to 18 months for both SE (5.0 ± 5.4 min) and ST (3.2 ± 4.7 min; p < 0.001) compared with OMC (0.2 ± 2.1 min, p = 0.04). The difference between SE and ST was not significant (p = 0.16). Improvement in claudication onset time (COT) was greater for SE compared with OMC, but not for ST compared with OMC. Many disease-specific quality-of-life scales demonstrated durable improvements that were greater for ST compared with SE or OMC. The authors concluded that both supervised exercise (SE) and stent revascularization (ST) had better 18-month outcomes than optimal medical care. SE and ST provided comparable durable improvement in functional status and in QoL up to 18 months. The authors state that durability of claudication exercise interventions merits its consideration as a primary PAD claudication treatment.

CMS also referenced the National Institute for Health and Care Excellence (NICE) 2014 update which recommends offering a supervised exercise program to all people with intermittent claudication. The guideline does not recommend any home-based exercise programs. Al-Jundi et al. (2013) did a systematic review of 17 studies of home-based exercise programs for people with intermittent claudication (n=1457). Home-based exercise was compared with supervised exercise in 5 studies, and was compared with usual care in 4 studies. One 3-arm study compared home-based exercise with both supervised exercise and with usual care. Seven studies had a single-group design. For home-based exercise compared with supervised exercise, 5 studies (n=382) reported that supervised exercise improved walking capacity and quality of life to a greater extent. Two of these 5 studies reported that home-based exercise resulted in little change from baseline.  In 1 additional study (n=119), improvements in walking capacity were higher in the supervised exercise group than in the home-based exercise group. Although these differences may have been clinically significant, they were not statistically significant. Overall 15 of the 17 included trials were rated as low quality. Limitations of individual studies included lack of description of randomization, no blinding of outcome assessors, small sample size, and recruitment to strict criteria in a single site, uncertainty about consistency of intervention delivery, no intention-to-treat analysis, and short-term follow-up (NICE, 2014). 

Key points in the NICE 2014 clinical evidence update include (Source: CMS, 2017):

  • Management of intermittent claudication - Exercise programs

    • Supervised exercise is associated with increases in maximal walking distance (MWD) compared with home-based or other unsupervised exercise programs.
    • Supervised exercise is associated with greater increases in walking distance in people with aorto-iliac disease than either stenting or optimum medical care.
    • Supervised exercise appears to be more cost effective than either angioplasty alone or supervised exercise plus angioplasty in people with IC due to femoro-popliteal occlusion.

CMS (2017) cited Vemulapalli et al. (2015) who conducted a systematic review and meta-analysis that included 28 articles from 27 studies (24 RCTs and 4 observational) with over 2,000 patient evaluations. The review assessed the comparative effectiveness of supervised exercise (SE) vs unsupervised exercise (UE) in patients with IC. Outcomes assessed were walking parameters, claudication parameters, patient-reported outcomes (from SF-36, peripheral artery questionnaire, and WIQ). The authors found that compared with UE, SE was associated with a moderate improvement in maximal walking distance at 6 months (p < .001) and 12 months (p < .001). Supervised exercise also improved claudication distance to a moderate extent compared with UE at 6 months (p < .001) and 12 months (p = .001). There was no statistical difference in the Short Form-36 quality of life at 6 months (p = .84) or walking impairment questionnaire distance (p = .08) or speed (p = .11). The authors concluded that SE is more effective than UE at improving maximal walking and claudication distances in patients with claudication; however, there was no difference in general QoL or patient-reported community-based walking. The authors reported that more studies are needed to investigate the relationship between functional gain and disease-specific QoL.  

American College of Cardiology (ACC)/American Heart Association (AHA) Practice Guideline (2016):

  • Recommendations for supervised exercise:

    • In patients with claudication, a supervised exercise program is recommended to improve functional status and QoL and to reduce leg symptoms. (COR I) (LOE A)
    • A supervised exercise program should be discussed as a treatment option for claudication before possible revascularization. (COR I) (LOE B-R)
       
  • Supervised exercise program definitions (COR I) (LOE A)

    • Program takes place in a hospital or outpatient facility
    • Program uses intermittent walking exercise as the treatment modality
    • Program can be standalone or within a cardiac rehabilitation program
    • Program is directly supervised by qualified healthcare provider(s)
    • Training is performed for a minimum of 30-45 minute/session; sessions are performed at least 3 times/week for a minimum of 12 weeks
    • Training involves intermittent bouts of walking to moderate-to-maximum claudication, alternating with periods of rest
    • Warm-up and cool-down periods precede and follow each session of walking

Society for Vascular Surgery (SVS) Practice Guideline (2015):

  • Recommendations for exercise therapy:

    •  “As first-line therapy a supervised exercise program consisting of walking a minimum of three times per week (30-60 min/session) for at least 12 weeks to all suitable patients with IC.” Grade 1; LOA: A
    • “Home-based exercise, with a goal of at least 30 minutes of walking three to five times per week when a supervised exercise program is unavailable or for long-term benefit after a supervised exercise program is completed.” Grade 1; LOE B
    • “In patients who have undergone revascularization therapy for IC, exercise (either supervised or home based) for adjunctive functional benefits.” Grade 1; LOE B

    (Source: CMS, 2017)

Per CMS (2017), “practice guidelines from the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) recommend SET as the initial treatment for patients suffering from IC (Gerhard-Hermanet et al, 2017).  While experts seem to agree that exercise therapy should be the initial treatment for PAD/IC, the number of endovascular revascularization (ER) procedures has been increasing (Spronk et al, 2008).  The preference of physicians and patients for the more invasive ER treatment can be partly attributed to the limited access to SET programs, and the immediate result that is observed with ER (Spronk et al, 2008; van den Houten et al, 2016).  ER has remained a more popular treatment option for claudication than SET, despite the ACCF/AHA recommendation that ER be reserved for cases where the patient is too functionally impaired for SET (Anderson et al, 2013)”.

Willens et al (2003) stated that abnormalities of peripheral arterial compliance are clinically useful markers of atherosclerosis and risk of vascular events.  Local peripheral arterial compliance can be easily and accurately assessed in the clinic by computer-controlled pulse volume recordings (air plethysmography).  These investigators examined the relationship between clinical cardiovascular risk factors, a surrogate of atherosclerotic burden, and peripheral arterial compliance in the thigh and calf determined by quantification of local pulse volume recordings in patients undergoing coronary angiography.  Peripheral arterial compliance in the thigh and calf was measured in 346 patients undergoing diagnostic cardiac catheterization at 4 centers.  Demographic and cardiovascular risk factor data were collected, and their relationship to local arterial compliance examined using a new device that assesses maximal local arterial volume change in an extremity segment.  Pulse volume recordings detected decreased local arterial compliance in the thigh associated with a history of hypertension (p < 0.0001), diabetes mellitus (p = 0.0001), and hyperlipidemia (p = 0.0007).  In the calf, this arterial compliance measure was associated with a history of hypertension (p < 0.0001) and diabetes mellitus (p = 0.002).  Females had lower arterial compliance than males in the thigh (p = 0.003) and calf (p < 0.0001).  Limited evidence of lower arterial compliance in the thigh was found for those with obesity (p = 0.07).  This procedure also demonstrated that subjects with multiple cardiovascular risk factors had lower arterial compliance in the thigh than subjects with no or 1 risk factor (p = 0.0001).  The authors concluded that peripheral arterial compliance determined by air plethysmography was strongly associated with standard cardiovascular risk factors.  The non-invasive measurement of local arterial compliance by regional pulse volume recording may be a useful adjunct for cardiovascular risk stratification early in the course of the disease as well as for monitoring vascular response to therapy.

Gerhard-Herman et al (2006) noted that accompanying the rapid growth of interest in percutaneous vascular interventions, there has been increasing interest among cardiologists in performing non-invasive vascular testing using ultrasound (US).  In an attempt to provide recommendations on the best practices in vascular laboratory testing, this report has been prepared by a writing group from the American Society of Echocardiography (ASE) and the Society for Vascular Medicine and Biology (SVMB).  The document summarized principles integral to vascular duplex US -- including color Doppler, spectral Doppler waveform analysis, power Doppler, and the use of contrast.  Appropriate indications and interpretation of carotid artery, renal artery, abdominal aorta, and peripheral artery US imaging were described.  A dedicated section summarized non-invasive techniques for physiologic vascular testing of the lower extremity arteries -- including measurement of segmental pressures and pulse volume plethysmography.  The use of exercise testing in the evaluation of PAD, US evaluation of the lower extremities after percutaneous re-vascularization, and the diagnosis and management of iatrogenic pseudoaneurysm was also discussed.

The QuantaFlo System (Digital ABI) for Screening of Peripheral Artery Disease

QuantaFlo (Semler Scientific, Inc.) is a novel, non-invasive, 510(k) Food and Drug Administration (FDA) cleared digital device that is used as a screening tool to measure ABI of patients at risk of PAD (NLM, 2018). 

Diage et al (2013) noted that PAD affects 8 to 18 million people in the United States; and patients with PAD are known to have increased morbidity and mortality.  The researchers said that medical guidelines recognize ankle brachial index (ABI) testing as an effective screening tool that allows for early detection of this disease in primary care settings.  The researchers noted that doppler ABI, the standard method used, is time-consuming and requires technical expertise.  Automated (digital) ABI testing through plethysmography may be a more attractive method in primary care settings due to its speed and ease of use.  In an observational study, these researchers evaluated the use of 1 digital ABI device in primary care settings to describe the population tested and the results obtained.  A total of 19 medical practices throughout the United States provided data on 632 patient tests.  In the population tested, the mean age was 67.2 (± 13.8) years, and 38 % of patients were men.  Additionally, 94.7 % of the population had risk factors, signs and/or symptoms suspicious for PAD, and 20.3 % presented with claudication; 12 % (76/632) of patient tests showed an abnormal digital ABI (less than 0.93), indicating a result positive for PAD; the frequency of hypercholesterolemia, hypertension, and coronary artery disease (CAD) in this group was 62 % (45/73), 69 % (50/72) and 46 % (34/74), respectively.  The authors concluded that the findings of this study supported the use of a digital ABI device using blood volume plethysmography technology for evaluation of PAD.  These findings were consistent with previously reported population characteristics with respect to PAD prevalence, signs/symptoms, and risk factors.  The authors concluded that the device used in this study enabled evaluation for PAD in primary care settings and may allow for early detection of the disease.  These researchers stated that further studies are needed to determine the benefit to other high-risk populations, such as diabetics, and to evaluate the correlation of digital ABI results using this device with definitive diagnostic techniques.

The authors stated that this study had several drawbacks.  First, the registry was designed to collect and described digital ABI results and patient history retrospectively, without pre-defined parameters.  One major limitation was the lack of direct comparison to Doppler ABI / definitive diagnostic techniques for each observation.  Doppler ABI data were not captured as part of the registry database, but is of primary importance for currently ongoing and future studies evaluating this new technology.  Second, the passive data collection method used meant that not all data on demographics, signs / symptoms, and risk factors could be collected for all patients.  Of the observations provided, 8 % had 1 or more missing data field.  All analyses were based on the number of fields completed for each variable of interest.  Third, this was an open data registry; thus, the clinical sites that provided data did so voluntarily.  The variation of clinical care settings allowed for data to be collected in “real world” settings, where a wide variety of patients were tested with the device.  As a consequence of this pragmatic approach, the data collection process did not include additional controls or data monitoring.  Risks of this method included missing data and possible errors during case report form completion.  No inclusion or exclusion criteria were applied; thus, the data set may be biased in either direction.  However, given the large number of patients tested and prevalence rates similar to other studies, the risk of patient selection bias was low.  Lastly, this study lacked follow-up or definitive diagnostics; therefore, this study did not address sensitivity and specificity of the digital ABI test.  These researchers stated that although the results were consistent with previous population-based studies; additional studies are needed to fully evaluate this technology.

Supervised Exercise Program on Individuals in Peripheral Arterial Disease with Type 2 Diabetes Mellitus

Arora and colleagues (2020) noted that type 2 Diabetes Mellitus (T2DM) is usually accompanied by various micro- and macro-vascular complications; and PAD is one of the major complications of diabetes that is accountable for morbidity and mortality throughout the world.  The first line of treatment in these patients with T2DM is life-style modification and exercise.  There is a dearth of evidence regarding the effect of supervised exercise program in PAD with T2DM on QoL, walking impairment, change in ABI values.  In a systematic review, these researchers examined the available literature on supervised exercise program in PAD with T2DM.  They carried out a systematic review (PubMed, Web of Science, CINAHL and Cochrane) to examine the evidence on a supervised exercise program in PAD with T2DM.  Randomized and non-randomized studies were included in the review.  A total of 3 studies met the inclusion criteria. The outcome measures of the included studies were the QoL, walking impairment questionnaire, and ABI.  None of the studies matched in their supervised exercise program nor in their outcome.  The authors concluded that the data evaluating the supervised exercise program in PAD with T2DM is inadequate to determine its effect on this population.  These researchers stated that future large-scale studies can be conducted on both subjective and objective outcomes of PAD with T2DM to have a better understanding of the condition and for a universally acceptable exercise program for these patients that the healthcare practitioners can use in their practice.

Transcutaneous Visible Light Hyperspectral Imaging (the HyperView System) for Wound Monitoring 

The HyperView system (HyperMed Imaging, Memphis, TN) is a hand-held, battery-operated, portable diagnostic imaging device that is used to evaluate tissue oxygenation without contacting the patient.   It is cleared via the FDA’s 501(k) process on December 16, 2016.  This tissue oximetry device is intended for use by physicians and healthcare professionals as a non-invasive tissue oxygenation measurement system that reports an approximate value of oxygen saturation (O2Sat), oxyhemoglobin level (oxy), and deoxyhemoglobin level (deoxy) in superficial tissue.  The HyperView system displays two-dimensional (2D), color-coded images of tissue oxygenation of the scanned surface.  Images and data provide hyperspectral tissue oxygenation measurements for selected tissue regions.  The device is indicated for use to determine oxygenation levels in superficial tissues for patients with potential circulatory compromise (e.g., peripheral vascular disease).

Nouvong and colleagues (2009) stated that foot ulceration remains a major health problem for diabetic patients and has a major impact on the cost of diabetes treatment.  In a prospective, single-arm, blinded study, these researchers tested a hyperspectral imaging (HIS) technology that quantifies cutaneous tissue hemoglobin oxygenation and generated anatomically relevant tissue oxygenation maps to examine the healing potential of diabetic foot ulcers (DFUs).  This trial was carried out in 66 patients with type 1 and type 2 diabetes and followed-up over a 24-week period.  Clinical, medical, and diabetes histories were collected.  Transcutaneous oxygen tension was measured at the ankles.  Superficial tissue oxy and deoxy were measured with HSI from intact tissue bordering the ulcer.  A healing index derived from oxy and deoxy values was used to evaluate the potential for healing.  A total of 54 patients with 73 ulcers completed the study; at 24 weeks, 54 ulcers healed while 19 ulcers did not heal.  When using the healing index to predict healing, the sensitivity was 80 % (43 of 54), the specificity was 74 % (14 of 19), and the positive predictive value (PPV) was 90 % (43 of 48).  The sensitivity, specificity, and PPVs increased to 86, 88, and 96 %, respectively, when removing 3 false-positive osteomyelitis cases and 4 false-negative cases due to measurements on a callus.  The results indicated that cutaneous tissue oxygenation correlated with wound healing in diabetic patients.  The authors concluded that HSI of tissue oxy and deoxy may predict the healing of DFUs with high sensitivity and specificity based on information obtained from a single visit.  These researchers stated that hyperspectral tissue oxygenation mapping has the potential to screen for lower-extremity complications due to diabetes.

Chin and associates (2011) noted that HSI is a novel technology that can non-invasively measure oxy and deoxy concentrations to create an anatomic oxygenation map.  It has predicted healing of DFUs; however, its ability to evaluate peripheral arterial disease (PAD) has not been studied.  In a prospective study, these researchers examined if HSI could accurately examine the presence or absence of PAD and accurately predict PAD severity.  This trial included consecutive consenting patients presenting to the vascular laboratory at the Jesse Brown VA Medical Center during a 10-week period for a lower extremity arterial study, including ABI and Doppler waveforms.  Patients with lower extremity edema were excluded.  Patients underwent HSI at 9 angiosomes on each extremity.  Additional sites were imaged when tissue loss was present.  Medical records of enrolled patients were reviewed for demographic data, active medications, surgical history, and other information pertinent to PAD.  Patients were categorized into no-PAD and PAD groups.  Differences in hyperspectral values between the groups were examined using the 2-tailed t test.  Analysis for differences in values over varying severities of PAD, as defined by tri-phasic, bi-phasic, or mono-phasic Doppler waveforms, was performed using 1-way analysis of variance.  Hyperspectral values were correlated with the ABI using a Pearson bi-variate linear correlation test.  The study enrolled 126 patients (252 limbs).  After exclusion of 15 patients, 111 patients were left for analysis, including 46 (92 limbs) no-PAD patients and 65 (130 limbs) PAD patients.  Groups differed in age, diabetes, coronary artery disease (CAD), congestive heart failure (CHF), tobacco use, and insulin use.  Deoxyhemoglobin values for the plantar metatarsal, arch, and heel angiosomes were significantly different between patients with and without PAD (p < 0.005).  Mean deoxy values for the same 3 angiosomes showed significant differences between patients with mono-phasic, bi-phasic, and tri-phasic waveforms (p < 0.05).  In patients with PAD, there was also significant correlation between deoxy values and ABI for the same 3 angiosomes (p = 0.001); oxy values did not predict the presence or absence of PAD, did not correlate with PAD severity, and did not correlate with the ABI.  The authors concluded that the findings of this study suggested the ability of HSI to detect the presence of PAD; and hyperspectral measurements could also evaluate different severities of PAD.

These researchers stated that HIS presents an interesting new development for the diagnostic imaging and evaluation of PAD.  Although this study did not provide an immediate breakthrough use for this technology at the bedside to replace existing technologies, this analysis has demonstrated its utility in distinguishing ischemia from normal flow states.  With further study and understanding of how this technology works, it may be a valuable tool for the prediction of wound healing in severely ischemic patients.  Other possible uses for HSI include monitoring and follow-up of re-vascularization interventions.  Future work concentrating on the recruitment of severe PAD and CLI patients should yield more immediately applicable results to the surgical management of tissue loss in those patients.  A robust study concentrating on the recruitment of severe PAD and CLI patients and analyzing its use in predicting the healing of PAD-associated tissue loss and need for re-vascularization or amputation should yield more immediately applicable results in the surgical management of tissue loss.  The clinical applicability of HSI with regards to PAD is clearly still in its adolescence and requires much more validation before it can be used safely and effectively.  However, this and other studies suggested an intriguing new opportunity for the physician and vascular laboratory.

Chiang and colleagues (2017) stated that HIS technology is a novel method of using transcutaneous measurement of oxy (HT-Oxy) and deoxy (HT-Deoxy) concentrations to create a 2D) color-coded "oxygen map".  In a prospective, pilot study, these researchers compared the use of a HSI device with the transcutaneous oxygen measurement (TCOM), ABI, and severity of peripheral vascular disease (PVD) and evaluated their correlations.  This trial enrolled 294 subjects divided into 3 distinct groups composed of healthy volunteers and patients with PVD.  Patients underwent measurements of lower limbs at a standardized point over the head of the first metatarsal on the plantar aspect using the HSI device, generating 4 outputs including HT-Oxy, HT-Deoxy, oxygen saturation (HT-Sat), and skin temperature, and the TCOM system, generating transcutaneous partial pressure of oxygen (TcpO2) and carbon dioxide (TcpCO2).  Demographic data, severity of PVD, ABI, and other pertinent information were obtained from both the subjects and medical records.  Inter-operator reliability ranged from 86 % to 94 % across the 4 HSI device outputs, whereas intra-operator reliability ranged from 92 % to 94 %.  The HT-Oxy, HT-Sat, TcpCO2, and ABI of the diseased limb correlated significantly with the severity of PVD.  HT-Sat significantly correlated with TcpO2 (R = 0.19), TcpCO2 (R = -0.26), ABI (R = 0.42), and skin temperature (R = 0.56); HT-Deoxy also correlated with TcpCO2 (R = 0.27).  The authors concluded that HSI represents a novel and validated method for measuring tissue oxygenation in patients with PVD.  The findings of this study demonstrated the reliability of the OxyVu device (a mobile HTCOM system) in comparison to TCOM, ABI, skin temperature, and severity of PVD in a large and extensive series of patients.  These results confirmed the ability of HSI in evaluating the presence of PVD and potential for use as a validated early screening tool.  Moreover ,these researchers stated that it may now be appropriate for further rigorous clinical evaluation of the OxyVu device for screening of arterial insufficiency, prediction of wound healing, detection of change in oxygenation after re-vascularization, evaluation of the potential for hyperbaric oxygen therapy, and differentiation between ischemic and neurogenic claudication.

The authors stated that this study had several drawbacks.  Only 2 target points were chosen, one at the plantar aspect of the head of the first metatarsal of the diseased foot and the other on the contralateral limb.  The average TcpO2 values from 2 or more adjacent sites of an area are better predictors of healing potential than single site values.  The plantar angiosome chosen at the head of the first metatarsal bone is covered by glabrous skin that is rich in arterio-venous anastomoses.  This skin tissue has more oxygenation and is more reactive to changes in oxygenation than skin on other parts of the body.  However, the skin in this area can be particularly thick.  In some individuals, this skin can be pathologically hypertrophic, taking the form of calluses or corns, which are common in patients with diabetic neuropathy.  OxyVu typically evaluates skin 1 to 2 mm in depth, and how this might have affected the findings of the validation study is unknown.  Although many of the correlation analyses were significant at p < 0.05, their clinical significance was unclear, given the relatively low correlation coefficient values.  Subjects with a history of lymphedema were excluded from the study.  However, it was possible that some may have had clinically significant leg edema that was not identified, given the subjective nature of quantifying this on examination.  A skin surface with underlying leg edema typically has less tissue oxygenation, precipitating the development of ulcers.  Furthermore, nearly 1/4 of the healthy volunteers in the study were active smokers but with a short-term history of smoking.  Although the impact of their smoking history on the measurements obtained is unknown, the ABIs recorded in this group were 0.9 to 1.2, highly suggestive of being normal.  Thus, the impact of both these factors could be assumed to not have been a large confounder in comparing oxygenation values in this study.

Wahabzada and colleagues (2018) noted that wound healing is a complex and dynamic process with different distinct and overlapping phases from homeostasis, inflammation and proliferation to re-modelling.  Monitoring the healing response of injured tissue is of high importance for basic research and clinical practice.  In traditional application, biological markers characterize normal and abnormal wound healing.  Understanding functional relationships of these biological processes is essential for developing new therapeutic strategies; however, most of the present techniques (in-vitro or in-vivo) include invasive microscopic or analytical tissue sampling.  In the present study, these researchers introduced a non-invasive alternative for monitoring processes during wound healing.  Within this context, HSI is an emerging and innovative non-invasive imaging technique with different opportunities in medical applications.  HSI acquires the spectral reflectance of an object, depending on its biochemical and structural characteristics.  An in-vitro 3-dimensional (3-D) wound model was established and incubated without and with acute and chronic wound fluid (AWF, CWF), respectively.  Hyperspectral images of each individual specimen of this 3-D wound model were evaluated at day 0/5/10 in-vitro, and reflectance spectra were examined.  For analyzing the complex hyperspectral data, an efficient un-supervised approach for clustering massive hyperspectral data was designed, based on efficient hierarchical decomposition of spectral information according to archetypal data points.  It represented, to the best of the authors’ knowledge, the first application of an advanced data mining approach in the context of non-invasive analysis of wounds using HSI.  By this, temporal and spatial pattern of hyperspectral clusters were determined within the tissue discs and among the different treatments.  Results from non-invasive imaging were compared to the number of cells in the various clusters, assessed by hematoxylin/eosin (H/E) staining.  It was possible to correlate cell quantity and spectral reflectance during wound closure in a 3-D wound model in-vitro.  Moreover, these researchers stated that further analysis targeting the specification of the cell condition and behavior as well as matrix composition during wound healing in relation to the spectral signature will provide deeper insights into the system.

The authors stated that in the next step, further analysis will be carried out to confirm these findings and to get more insight into the interpretation of HSI data on the cellular and molecular level in detail.  With this extended information pool achieved by using HSI as a new diagnostic tool, the clinician will be able to specifically adapt the therapeutic management to improve the outcome of wound healing or prevent the aggravation of diseases, respectively.  Furthermore, it is expected, that due to the current progress in sensors and machine learning technologies, new and powerful tools for human medicine are provided; these may be easy-to-use hand-held sensors with integrated analysis routines for an immediate decision support.

Li and co-workers (2020) noted that chronic wounds affect millions of patients worldwide, placing a huge burden on health care resources.  Although significant progress has been made in the development of wound treatments, very few advances have been made in wound diagnosis.  Standard imaging methods like computed tomography (CT), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), terahertz (THz) imaging, and ultrasound (US) imaging have been widely employed in wound diagnostics.  Several non-invasive optical imaging modalities like optical coherence tomography (OCT), near-infrared spectroscopy (NIRS), laser Doppler imaging (LDI), spatial frequency domain imaging (SFDI), digital camera imaging, HSI as well as thermal and fluorescence imaging have emerged over the years.  While standard diagnostic wound imaging modalities provide valuable information, they could not account for dynamic changes in the wound environment.  Furthermore, they lack the capability to predict the healing outcome; therefore, there remains a pressing need for more efficient methods that can not only indicate the current state of the wound but also help ascertain if the wound is on track to heal normally.  HSI is a non-invasive optical imaging modality that can capture a series of images, recording the intensity of diffusely reflected light from the wounded tissue, and generate a 3-D data cube.  Using halogen lamps or light-emitting diodes as light sources and charge-coupled device or hyperspectral camera as detectors, HSI can quantify factors including oxy, deoxy, and blood oxygen saturation; thus, reflecting the extent of wound oxygenation.  Perfusion parameters, such as oxygenated hemoglobin, deoxygenated hemoglobin, and total hemoglobin, measured by HSI has been used to distinguish burn depth (intermediate dermal, deep dermal, and full thickness) in a murine burn wound model.  The ability of HSI to differentiate these levels of burn injury was verified by histology.  By generating anatomical wound oxygen maps, this technique can evaluate healing potential of DFUs.  Overall, HSI is capable of identifying microvasculature abnormality and tissue oxygenation in chronic wounds, despite its limited imaging depth.  The authors concluded that many imaging probes have been fabricated and shown to provide real-time assessment of tissue micro-environment and inflammatory responses in-vivo.  These probes have been demonstrated to non-invasively detect various changes in the wound environment, which include tissue pH, reactive oxygen species, fibrin deposition, matrix metalloproteinase production, and macrophage accumulation.  They noted that optical imaging techniques have emerged as a potential alternative in wound monitoring.  Moreover, these researchers stated that to meet the needs of the growing wound care market, there is tremendous opportunity to translate optical imaging discoveries for chronic wound diagnosis and monitoring with speed, precision, real-time responsiveness, portability, and smartphone capability.  With all these advancements, it is conceivable that optical wound imaging may play a pivotal role in routine wound care in clinics in the very near future.

Chan and Lo (2020) stated that patients with diabetes mellitus have a lifetime risk of 15 % to 25 % of developing DFUs, which are associated with significant morbidity and mortality.  Wound imaging systems are useful adjuncts in monitoring of wound progress.  In a systematic review, these investigators examined existing literature on the available wound assessment and monitoring systems for DFUs.  They searched for pertinent articles from PubMed and Embase (1974 to March 2020).  All studies related to wound assessment or monitoring systems in DFUs were included.  Articles on other types of wounds, review articles, and non-English texts were excluded.  Outcomes include clinical use, wound measurement statistics, hospital system integration, and other advantages and challenges.  The search identified 531 articles; 17 full-text studies were eligible for the final analysis.  A total of 5modalities were identified: computer applications or hand-held devices (n = 5); mobile applications (n = 2); optical imaging (n = 2); spectroscopy or HSI (n = 4), and artificial intelligence (n = 4).  Most studies (n = 16) reported on wound assessment or monitoring.  Only 1 study reported on data capturing; 2 studies on the use of computer applications reported low inter-observer variability in wound measurement (inter-rater reliability of greater than 0.99, and inter-observer variability 15.9 %, respectively).  Hand-held commercial devices demonstrated high accuracy (relative error of 2.1 % to 6.8 %).  Use of spectroscopy or HSI in prediction of wound healing has a sensitivity and specificity of 80 % to 90 % and 74 % to 86 %, respectively.  Majority of the commercially available wound assessment systems have not been reviewed in the literature on measurement accuracy.  The authors concluded that rapid advancement in technology has led to the development of various types of wound assessment and monitoring systems that serve as useful adjuncts in improving clinical care, with various products documenting superior accuracy over traditional methods of wound assessments.  In line with this, it is prudent to have ongoing studies to examine the evidence and outcomes of the extensive list of commercially available wound assessment and monitoring systems.

Dietrich and associates (2020) stated that normalization of macro-circulatory parameters during resuscitation therapy does not guarantee the restoration of micro-circulatory perfusion in critical illness due to hemodynamic incoherence.  Persistent micro-circulatory abnormalities are associated with severity of organ dysfunction and mandate the development of bedside micro-circulatory monitoring.  A novel HIS system can visualize alterations in skin perfusion, oxygenation and water content at the bedside.  These researchers described a study protocol that will examine the effectiveness of HSI for bedside monitoring of skin micro-circulation and the association of HSI parameters with organ dysfunction in patients with sepsis and major abdominal surgery.  A total of three independent groups will be evaluated and separately analyzed within a clinical prospective observational study.  The first group will include 25 patients with sepsis or septic shock (according to sepsis-3 criteria); the second group will include 25 patients undergoing pancreatic surgery, and the third group will include 25 healthy controls.  Patients with sepsis and patients undergoing pancreatic surgery will receive standard therapy according to local protocols derived from international guidelines.  Furthermore, cardiac output of peri-operative patients and patients with sepsis will be measured.  Healthy controls undergo one standardized evaluation.  The TIVITA Tissue System is a novel HSI system that employs the visible and near-infrared spectral light region to determine tissue micro-circulatory parameters.  HSI analysis (hand/knee) will be carried out in parallel to hemodynamic monitoring within defined intervals during a 72-hour observation period.  HSI data will be correlated with the Sequential Organ Failure Assessment score, global hemodynamics, inflammation and glycocalyx markers, surgical complications and 30-day outcome.  These researchers stated that this protocol has been approved by the local ethics committee of the University of Heidelberg (S-148/2019); study results will be submitted to medical conferences for presentation and to peer-reviewed journals for publication.

Table: CPT Codes / HCPCS Codes / ICD-10 Codes
Code Code Description

Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":

CPT codes covered if selection criteria are met:

93668 Peripheral arterial disease (PAD) rehabilitation, per session

CPT codes not covered for indications listed in the CPB:

PADnet system, QuantaFlo System - no specific code:

ICD-10 codes covered if selection criteria are met:

I70.211 - I70.219 Atherosclerosis of native arteries of extremities with intermittent claudication
I70.311 - I70.319 Atherosclerosis of unspecified type of bypass graft(s) of the extremities with intermittent claudication
I70.611 - I70.619 Atherosclerosis of nonbiological bypass graft(s) of the extremities with intermittent claudication
I70.711 - I70.719 Atherosclerosis of other type of bypass graft(s) of the extremities with intermittent claudication
I73.00 - I73.9 Peripheral vascular diseases

ICD-10 codes not covered for indications listed in the CPB:

Z13.6 Encounter for screening for cardiovascular disorders [screening of peripheral artery disease]

Transcutaneous visible light hyperspectral imaging (HyperView) :

CPT codes not covered for indications listed in the CPB:

0631T Transcutaneous visible light hyperspectral imaging measurement of oxyhemoglobin, deoxyhemoglobin, and tissue oxygenation, with interpretation and report, per extremity

ICD-10 codes not covered for indications listed in the CPB:

I73.0-I73.9 Peripheral vascular diseases

The above policy is based on the following references:

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