KEY PERSPECTIVES
What is novel?
* This study evaluates the clinical effectiveness of the exercise prescription and selection algorithms published by the American Heart Association (AHA) and the American Association of Cardiovascular and Pulmonary Rehabilitation and Prevention (AACVPR) that are recommended for use in clinical supervised exercise therapy (SET) programs.
* This study addresses two additional research priorities for exercise interventions in patients with PAD as outlined in the 2019 Scientific Statement from the AHA by (1) evaluating the optimal form of exercise for individual patients through incorporation of personalized selection of exercise and (2) employing a translational science approach to SET with a real-world clinical population.
What are the clinical and/or research implications?
* This is the first study to directly show that SET programs that follow AHA and AACVPR exercise prescription guidelines housed in cardiac rehabilitation settings improve clinically important outcomes for symptomatic PAD.
* Future studies that investigate the effects of clinically based SET programs using AHA and AACVPR best practices on clinically important outcomes, similar to this study, are further needed to establish benchmarks for SET program success.
Lower extremity peripheral artery disease (PAD) affects 5.8-10.7% of people in the United States >40 yr of age.1 Individuals with PAD have greater functional impairment, more rapid functional decline, and higher rates of mobility loss than those without PAD.2-4 Supervised exercise therapy (SET) is a cornerstone of treatment for improving walking capacity and physical function for individuals with claudication.5,6 Since SET has only recently become a reimbursable service through the Centers for Medicare & Medicaid Services,7 its clinical effectiveness in the US clinical rehabilitation setting is still unknown. Specifically, it is unknown how effective the current expert opinion-based SET guidelines are when implemented in clinical practice.6,8 Currently, aerobic exercise is the focus of SET, with the gold standard modality being intermittent treadmill walking training (TM walking) to moderate levels of claudication.9,10 However, TM walking is not feasible in some patients with PAD who enroll in SET.6 Other possible aerobic exercise modalities that may be utilized include stationary cycling, upper-body ergometry (UBE), and total body recumbent stepping (TBRS).
Current SET guidelines state that aerobic exercise therapy should be individualized to help ensure that all patients wishing to participate see as much benefit as possible.6,8 An important consideration is selection of an appropriate primary aerobic exercise training modality that is guided by the exercise provider.6,8,9 To date, no study has investigated the clinical effectiveness of guideline-directed exercise prescription that reflects current American Heart Association (AHA)6 and American Association of Cardiovascular and Pulmonary Rehabilitation and Prevention (AACVPR)8 recommendations. As clinical SET programs are now being established, this necessitates a need for translational SET studies that moves from T2 (clinical research study) to T3 (translating to practice with clinical outcomes research) phases. To address these research gaps, the purpose of this translational study was to evaluate the clinical effectiveness of a SET program conducted in four rural Midwestern cardiac rehabilitation (CR) facilities that reflect current implementation guidelines for exercise selection and prescription.
METHODS
The parent study for this research, the PAD PRAIRIE Initiative, was a 4-yr (2015-2019) outreach initiative funded by the Margaret A. Cargill Foundation. The PAD PRAIRIE Initiative was aimed at improving awareness, detection, and treatment of PAD in the rural Midwest. While the initiative was predominantly focused on outreach, a research component measured pre/post-test outcomes of SET programs using a prospective, quasi-experimental, nonequivalent groups design. The program, housed in four existing CR programs in rural Minnesota, was reflective of AHA6 and AACVPR guidelines8 and delivered by trained exercise physiologists and nurses. All methods were approved by the University of Minnesota Institutional Review Board (IRB; 1510S78885 Healthy Aging and Mobility Initiative). All sites were covered by the University of Minnesota IRB.
The sample included individuals who had been identified through community screenings or by their health care providers as having a positive ankle-brachial index (ABI) and who were without contraindications to exercise.11 All participants received a referral from a health care provider to the SET program. Everyone referred to the program received clinical care irrespective of their study participation. Informed consent was obtained before participation. Inclusion criteria were age >=18 yr, an ABI of <=0.90, or a verified clinical history and current symptoms of PAD. Individuals with New York Heart Association class IV heart failure, uncontrolled sustained arrhythmias, severe/symptomatic aortic or mitral stenosis, hypertrophic obstructive cardiomyopathy, severe pulmonary hypertension, or other conditions aggravated by exercise, such as uncontrolled hypertension (>=200 mm Hg systolic blood pressure and/or diastolic blood pressure >=100 mm Hg), ischemic rest leg pain and/or leg/foot ulceration, or impending gangrene, were excluded.
Outcome Assessments
Data on walking capacity, physical function, and quality of life (QOL) outcomes were collected at baseline (time of enrollment) and at approximately 3-mo follow-up in an attempt to mimic Centers for Medicare & Medicaid Services-reimbursed CR programs.
The 6-min walk test (6MWT) was administered following standard guidelines.12 Briefly, participants were instructed to walk as fast as possible along a linear marked course, turn around a marker cone, and then return in the opposite direction and to repeat this loop as often as possible for 6 min. The number of laps completed was tabulated and used in the calculation of total distance walked. The length of the courses used for the 6MWT varied between sites 100-200 ft (30.5-61 m). However, the 12-wk 6MWT was conducted on the same course as used during baseline testing for all participants.
The 4-m walk test (4mWT) was performed according to standard instructions.13,14 Participants performed two trials, with the time of both trials averaged and converted to speed in m/sec (usual gait speed).
The timed up-and-go (TUG) test was administered as follows: Participants were instructed to sit with their back against the back of a standard padded chair (43.2 cm) without armrests. Subsequently, they were given the following instructions: "On command stand up from a chair, walk 3 m at your usual pace past a line on the floor, turn around, walk back to the chair, and sit down again with the back against the chair.15 The TUG test is a valid test for assessment of dynamic balance and fall risk in older adults.16
The repeated chair rise (RCR) was administered as follows: Participants were instructed to sit with their back against the back of a standard padded chair (43.2 cm) without armrests. Subsequently, they were given the following instructions: "Please stand up straight as quickly as you can 5 times, without stopping in between. Keep your arms folded across your chest." Timing with a stopwatch began upon the initial upward movement of the participant and stopped when the participant achieved the seated position after the fifth repetition.13
Assessment of QOL was made using the PAD Quality of Life Questionnaire (PADQOL), a 38-item questionnaire designed to specifically examine PAD-related QOL.17 The PADQOL contains five factors: social relationships and interactions, self-concept and feelings, symptoms and limitations in physical functioning, fear and uncertainty, and positive adaptation, in addition to three individual items on sexual function, intimate relationships, and job function. Higher scores on the PADQOL indicate greater QOL.
Experimental Protocol
SET Intentions
The PAD PRAIRIE Initiative SET program mirrored the Centers for Medicare & Medicaid Services recommendations7 and was reflective of AHA and AACVPR guidelines.6,8 Site coordinators and study staff used the training algorithm in the protocol to help with the appropriate selection of exercise modality and subsequent progression of exercise program.6,9 Exercise was prescribed by therapists (ie, exercise physiologists and nurses) based on safety, physical functioning, and patient preference.9 Each site used the same algorithm, had access to the same exercise equipment, and received the same instructions regarding exercise prescription. However, therapists were allowed to use their clinical judgment to adjust the exercise prescription as needed, based on individual patient signs and symptoms.6,9 Sessions of SET were held in CR facilities three times/wk (dependent on the site) for 12 wk; all sessions were 60 min in length. Participants were encouraged to increase their daily physical activity, but recommendations were not structured or monitored. Site coordinators communicated weekly with a clinical exercise physiologist and nurses at the urban academic health center to review protocol compliance.
Treadmill Walking Group (TM Walking)
Individuals in the TM walking group performed their exercise program at a self-paced speed while the incline (ie, intensity) was adjusted to induce moderate claudication (rated 3-4 on a scale of 0-5) within 5-10 min. Participants were then instructed to rest until pain subsided at which point, they began another walking bout at the same intensity. Exercise/rest cycles were repeated throughout each 60 min exercise session. Once a participant achieved >=10 min of continuous walking at the initial workload, the treadmill speed or grade was increased by increments of 0.1 mph or 1% in the subsequent training session based on participant preference and tolerability. This intensity progression scheme was continued for the duration of the intervention.
Total Body Recumbent Stepping Group (TBRS)
TBRS was performed on TRS 400 T4 Cross Trainers (NuStep). Exercise prescriptions differed on the basis of whether the exercise training modality induced claudication. Participants were encouraged to select a comfortable stepping rate and resistance that induced moderate effort (assessed by rating of perceived exertion [RPE]), while maintaining full range of motion at the knee and hip joints. For participants who experienced claudication during TBRS, the exercise prescription and progression mirrored that of the TM walking group. For individuals who did not develop claudication during TBRS, TBRS exercise prescriptions were based on current CR guidelines to improve aerobic fitness.9,18 Specific intensity targets were determined on the basis of the Borg Category Rating (CR)-15 Scale, with RPE targets of 11-12 for wk 1, which progressed to 14-15 by wk 10.
Combination Exercise 1 (TM Walking + TBRS)
Participants were included in this group if they performed one or more bouts of TM walking in each session, with the remaining session dedicated to TBRS. Exercise prescriptions followed guidelines for TM walking and TBRS as outlined earlier. To be considered in the combination group, in each session, participants had to complete one or more bouts of TM and one TBRS bout. However, this was not standardized and there was intra- and interindividual variability in the number of treadmill bouts completed per session in the SET program. Therefore, exercise duration on either modality varied on a participant-by-participant basis.
Combination Exercise 2 (Multimodal)
Participants were included in this group if their combination exercise did not involve strictly TM walking and TBRS. Therefore, the potential combination of exercise modalities used in this group included (1) TM + TBRS + UBE, (2) TBRS + UBE, or (3) TM + UBE. In addition, some of these participants incorporated resistance training as well into their multimodal programs. TM and TBRS exercise prescriptions followed those listed in the TM + TBRS group. The UBE exercise prescription followed current guidelines.6,9 Participants who performed resistance training utilized body weight or free-weight training targeting both upper- and lower-body muscle groups.6 Participants were encouraged to choose a load that reflected moderate intensity based on RPE. Again, the number of sessions and the duration employing TM, TBRS, UBE, or resistance training were not standardized and there was intra- and interindividual variability.
Statistical Analyses
The normality of data distribution and the homogeneity of variance were evaluated using the Shapiro-Wilks and Levene tests, respectively. Baseline values and change scores for the 4mWT and the TUG test were log transformed to normalize the distribution due to large positively skewed standard deviations. At baseline, group characteristics were compared by an analysis of variance (continuous variables) or the chi-square test (categorical variables) unless small cell counts existed, in which case the Fischer exact tests were used. Paired t tests were used to examine differences between baseline and follow-up in outcome variables for the entire group. Differences between groups in the primary endpoint (6MWT) and secondary endpoints: 4mWT, RCR, TUG test, and PADQOL following SET were assessed using analysis of covariance with baseline values for each of these variables. Statistical significance was considered to be P < .05. All data were analyzed using SPSS version 28.0 (IBM Corp).
RESULTS
A total of 96 participants initially expressed interest in the SET program (and study), 93 enrolled (site 1: n = 56; site 2: n = 9; site 3: n = 4; site 4: n = 24) and were evaluated for appropriate exercise mode using the previously mentioned algorithm.9 This resulted in the following breakdown by exercise modality: TM walking (n = 28), TBRS (n = 20), TM walking + TBRS (n = 25), and multimodal (n = 20). Of the 93 who enrolled, 57 participants completed the 12-wk SET program, 27 dropped out, and nine did not complete the 12-wk assessments (Figure).
The sample (n = 93) was all White, with 55% female representation, age of 73.7 +/- 9.0 yr, and mild to moderate PAD (ABI = 0.71 +/- 0.19). Demographic and clinical differences across groups are summarized in Table 1. Overall, the TBRS group had significantly poorer walking capacity and physical function at baseline including the 6MWT (P < .01), TUG test (P < .01), and gait speed (P < .01) than the TM walking and TM walking + TBRS groups but not the multimodal group. No significant differences in walking capacity or physical function were seen at baseline among the TM, TM + TBRS, and multimodal groups.
Collectively, session adherence (of available 36 sessions attended) was 55.9 +/- 29.6% (70.8 +/- 20.0% for non-dropouts). Group-based session adherence was 52.0 +/- 30.1%, 58.5 +/- 25.4%, 64.0 +/- 28.6%, and 47.9 +/- 33.3% (P = .34) for the TM walking, TBRS, TM walking + TBRS, and multimodal groups, respectively. When removing the dropouts (n = 27), session adherence was 73.1 +/- 22.9%, 66.6 +/- 16.6%, 73.0 +/- 20.6%, and 69.9 +/- 21.3% for the TM walking, TBRS, TM walking + TBRS, and multimodal groups, respectively. Group-based differences remained insignificant (P = .77). The number of dropouts was not significantly different among modalities (P = .12).
Collectively (n = 57), SET significantly improved the 6MWT (32.1 +/- 6.6 m; P < .01) (Cohen's d = 0.66) and TUG (-1.86 +/- 0.56 sec; P < 0.01) (Table 2). The SET attendance was not significantly associated with change in the 6MWT (r =-0.04, P = .80). In addition, SET significantly improved three of five factors on the PADQOL including factor 3: symptoms and limitations of physical functioning (2.66 +/- 1.01; P = .01), factor 4: fear and uncertainty (1.78 +/- 0.62; P < .01), and factor 5: positive adaptation (1.49 +/- 0.76; P = .05) (Table 3).
Following SET, there were no significant between-group differences in change scores for the 6MWT in the TBRS (33.9 +/- 11.1 m), TM walking + TBRS (40.7 +/- 10.4 m), or multimodal (11.1 +/- 19.5 m) groups compared with the TM walking group (36.9 +/- 13.2) (P = .30; partial [eta]2 = 0.072). The TM walking (P = .02, .05), TBRS (P = .02, .04), and TM walking + TBRS (P = .01, .03) groups significantly improved the TUG test and RCR, respectively, compared with the multimodal group, but no significant differences were seen in between-group comparisons for the TM walking, TBRS, and TM walking + TBRS groups. No significant between-group changes for gait speed or individual factors of the PADQOL were found. All group-based analyses were adjusted for baseline values. Further adjustments for session adherence (ie, attendance) did not affect change scores or P values.
DISCUSSION
The primary finding of this study was that a clinically based SET program that delivered guideline-directed exercise prescription enhanced walking capacity, physical function, and QOL in persons with symptomatic PAD. Improvements in the 6MWT shown in this study reflect those of a previous nonrandomized study where 36 participants who completed a similar clinically based SET program significantly increased the 6MWT by 35 m.19 Participants in this study experienced improvements in the 6MWT of 36.9, 33.9, and 40.7 m (TM walking, TBRS, and TM walking + TBRS groups, respectively), which all represent large meaningful changes, as defined in patients with PAD by McDermott and colleagues20 as 20 m. In addition, the lack of significant differences regarding between-group change scores for the 6MWT provides support for the use of non-TM walking exercise modalities in SET.
Other important implications of this research include findings related to the TBRS and TM walking + TBRS groups. Based on the significantly lower 6MWT at baseline for the TBRS group relative to the TM walking and TM walking + TBRS groups, the results could be interpreted in different ways. One thought is that the lower baseline walking capacity in the TBRS group led to a greater potential for improvement (or the higher walking capacity in the TM walking and TM walking + TBRS groups a lower potential for improvement [ie, diminishing returns]). Regardless, the TBRS group demonstrated significantly greater physical function limitations and, despite these limitations, was able to still achieve a large, meaningful change in the 6MWT. The multimodal group was outperformed by the other three training groups pertaining to changes in gait speed and RCR and also had the lowest change score for the 6MWT. Only speculations can be made to why this occurred. Participants in this group had the potential to try a variety of different exercise modalities, with several participants stating this would help prevent potential boredom. However, multimodal approach can provide inherent challenges in regard to providing structure and adherence to exercise prescription algorithms, specifically with application of the overload principle, which can be easier to employ and document when limiting exercise to one or two modalities.
The primary strength of this study is that it reflected the clinical practice of exercise prescription in SET programs and utilized state-of-the-science algorithms for exercise modality selection and progression.6,9 This study addresses a research priority for non-TM exercise interventions in persons with PAD as outlined in the 2019 Scientific Statement from the AHA.10 There are a few limitations that should be noted in addition to the sample size. First, as outlined earlier, treatment was not randomized and this was not a controlled trial. The investigators wished to (1) design the study so that it replicated current practices of SET programs and (2) did not wish to withhold therapy (ie, wait-list control) from patients, given the great success of SET, especially when compliance is high. Second, because of inconsistent recording in exercise logs, quantification of session exercise time, total exercise time, average session intensity (RPE), average SET intensity, and therefore exercise dose, across groups could not be accurately quantified. Issues with transcription of exercise logs have been reported previously in clinical SET programs.8,9 Finally, we did not measure physical activity outside of the supervised setting or exercise dose achieved during SET, so it is possible that dose or outside physical activity may have been a confounding influence on improvements, although it is well known that persons with PAD report low habitual physical activity.21-23
CONCLUSION
Clinically implemented SET programs that follow current AHA and AACVPR guidelines for exercise selection and prescription have the potential to improve walking capacity, physical function, and QOL in persons with symptomatic PAD. Individuals who are prescribed a TBRS-based exercise modality or in combination with TM walking can see improvements in walking capacity, physical function, and QOL to a similar extent as with TM training alone. Future, larger-scale studies conducted in clinical SET programs using guideline-directed exercise prescriptions should be conducted to replicate these findings.
ACKNOWLEDGMENT
This study was supported by the Healthy Aging and Mobility Initiative funded by the Margaret A. Cargill Foundation.
REFERENCES