Effects of Exercise Training Response on Quality of Life and Cardiovascular Risk Factor Profiles in People With Coronary Artery Disease: Insights From the HIIT or MISS UK Trial.

OBJECTIVE: To compare the characteristics of responders and nonresponders to 8 weeks of exercise training to determine differences in key cardiovascular disease outcomes in people with coronary artery disease (CAD). DESIGN: Secondary analysis of data from the HIIT or MISS UK trial. SETTING: Six outpatient National Health Service cardiac rehabilitation (CR) centers in the UK. In people with CAD attending CR, the HIIT or MISS UK trial reported that short-term, low-volume, high-intensity interval training (HIIT) was more effective than moderate-intensity steady state (MISS) exercise training for improving peak oxygen uptake (V̇o2peak). PARTICIPANTS: 382 participants with CAD (N=382) (mean age: 58.8±9.6y; mean body mass index: 29.0±4.3 kg/m2). MAIN OUTCOME MEASURES: We identified responders and nonresponders based on a meaningful change in V̇o2peak, using 2 established methods. Key clinical, quality of life (QoL), and cardiopulmonary exercise test (CPET)-derived outcomes were compared between groups. RESULTS: Responders were more likely to be younger (P<.05), and demonstrate greater improvement in CPET-related outcomes, for example, oxygen uptake efficiency slope, ventilatory efficiency, and peak power output (all comparisons, P<.001). Responders were more likely to observe improvements in QoL (EQ-5D-5L; mean Δ 13.6 vs mean Δ 9.4; P=.045), and high-density lipoprotein cholesterol (HDL-c) (mean Δ 0.09 mmol/L vs mean Δ 0.04 mmol/L; P=.004), compared to nonresponders. CONCLUSIONS: In people with CAD attending CR, responders to exercise training were more likely to be younger and demonstrate greater improvements in health-related QoL and HDL-c.

Cost-effectiveness of High-Intensity Interval Training (HIIT) vs Moderate Intensity Steady-State (MISS) Training in UK Cardiac Rehabilitation.

OBJECTIVE: To perform a cost-effectiveness analysis of high-intensity interval training (HIIT) compared with moderate intensity steady-state (MISS) training in people with coronary artery disease (CAD) attending cardiac rehabilitation (CR). DESIGN: Secondary cost-effectiveness analysis of a prospective, assessor-blind, parallel group, multi-center RCT. SETTING: Six outpatient National Health Service cardiac rehabilitation centers in England and Wales, UK. PARTICIPANTS: 382 participants with CAD (N=382). INTERVENTIONS: Participants were randomized to twice-weekly usual care (n=195) or HIIT (n=187) for 8 weeks. Usual care was moderate intensity continuous exercise (60%-80% maximum capacity, MISS), while HIIT consisted of 10 × 1-minute intervals of vigorous exercise (>85% maximum capacity) interspersed with 1-minute periods of recovery. MAIN OUTCOME MEASURES: We conducted a cost-effectiveness analysis of the HIIT or MISS UK trial. Health related quality of life was measured with the EQ-5D-5L to estimate quality-adjusted life years (QALYs). Costs were estimated with health service resource use and intervention delivery costs. Cost-utility analysis measured the incremental cost-effectiveness ratio (ICER). Bootstrapping assessed the probability of HIIT being cost-effective according to the UK National Institute for Health and Care Excellence (NICE) threshold value (£20,000 per QALY). Missing data were imputed. Uncertainty was estimated using probabilistic sensitivity analysis. Assumptions were tested using univariate/1-way sensitivity analysis. RESULTS: 124 (HIIT, n=59; MISS, n=65) participants completed questionnaires at baseline, 8 weeks, and 12 months. Mean combined health care use and delivery cost was £676 per participant for HIIT, and £653 for MISS. QALY changes were 0.003 and -0.013, respectively. For complete cases, the ICER was £1448 per QALY for HIIT compared with MISS. At a willingness-to-pay threshold of £20,000 per QALY, the probability of HIIT being cost-effective was 96% (95% CI, 0.90 to 0.95). CONCLUSION: For people with CAD attending CR, HIIT was cost-effective compared with MISS. These findings are important to policy makers, commissioners, and service providers across the health care sector.

Home-based Circuit Training and Community Walking for Intermittent Claudication.

BACKGROUND: Supervised exercise training is recommended for people with peripheral artery disease (PAD), yet it remains underutilized. Home-based exercise programs (HBEPs) are a potential alternative. The aim of this study was to assess the feasibility of conducting a full scale trial of a 12-week HBEP for people living with symptomatic PAD. METHODS: In a randomized feasibility trial, patients with intermittent claudication were allocated to either an HBEP or a nonexercise control. The HBEP group was given a Fitbit to use during a 12-week exercise program comprising of personalized step goals and a resistance-based circuit to be undertaken at home twice weekly. The primary outcome was feasibility, assessed via eligibility, recruitment, attrition, tolerability, and adherence. Acceptability was assessed via semistructured interviews. Secondary analysis was undertaken to determine the feasibility of collecting clinical outcome data. RESULTS: 188 people were screened, 133 were eligible (70.7%), 30 were recruited (22.6%) and one withdrew (3.33%). Mean adherence to the daily step goal was 53.5% (range = 29.8-90.5%), and 58.6% of prescribed circuits were completed of which 56.4% were at the desired intensity. Six adverse events were recorded, 3 of which were related to study involvement. No significant differences were observed in exploratory outcomes. Small clinically important differences were seen in walking speed and pain-free treadmill walking distance which should be confirmed or refuted in a larger trial. CONCLUSIONS: The HBEP was feasible and well tolerated, with successful recruitment and minimal attrition. The intervention was acceptable, with walking seen as more enjoyable than circuit exercise. The WALKSTRONG program may be suitable for those who will not, or cannot, take part in supervised exercise outside of the home.

A systematic review of exercise intervention reporting quality and dose in studies of intermittent claudication.

BACKGROUND: Exercise therapy is an important treatment option for people with intermittent claudication (IC). Appropriate reporting of exercise interventions in populations with IC within randomised controlled trials (RCTs) is important to ensure that research can be translated into clinical practice. Therefore, the purpose of our review is to evaluate the reporting of exercise interventions in RCTs of exercise therapy in patients with IC. METHODS: A systematic search was performed to identify relevant trials in patients with IC published until May 2020. Studies including only participants with critical limb ischaemia or asymptomatic peripheral artery disease were excluded. Each trial was scored using the recently developed 'Consensus on Exercise Reporting Template' (CERT) which has a maximum obtainable score of 19. RESULTS: Of 1489 unique records identified from the search, 73 trials were included, reporting 107 exercise interventions. Overall, the average CERT score was 10/19. The exercise equipment used, the use of supervision and a description of whether the exercise prescription was tailored or generic were the most frequently reported intervention components. The motivational strategies used, intervention adherence and intervention fidelity were the most underreported CERT components. There was no trend indicating that CERT scores were higher in more recent publications. CONCLUSIONS: We have identified that important details about exercise interventions are frequently missing from the published literature. These missing data hinder replication of research findings and limit the translation of evidence into clinical practice.

Safety of home-based exercise for people with intermittent claudication: A systematic review.

Intermittent claudication (IC) is a classic symptom of peripheral artery disease, with first line treatment being supervised exercise therapy (SET). Despite this, SET is frequently underutilised, and adherence is often poor. An alternative option are home-based exercise programmes (HBEP). Although HBEPs are well tolerated, to the authors' knowledge, no research has assessed their safety. The aim of this review was to assess the safety of HBEPs in people living with IC. We performed an electronic search of the MEDLINE, CINAHL, and Cochrane Library databases. The main parameter of interest was complication rate, calculated as the number of related adverse events per patient-hours. Subanalysis was undertaken to determine differences in safety for studies that did and did not include pre-exercise cardiac screening, and for studies with exercise at low, moderate, and high levels of claudication pain. Our search strategy identified 8693 results, of which 27 studies were included for full review. Studies included 1642 participants completing 147,810 patient-hours of home-based exercise. Four related adverse events were reported, three of which were cardiac in origin, giving an all-cause complication rate of one event per 36,953 patient-hours. Three of these events occurred following exercise to high levels of claudication pain, and one occurred with pain-free exercise. One event occured in a study without cardiac screening. Based on the low number of related adverse events, HBEPs appear to be a safe method of exercise prescription for people with IC. Our results strengthen the rationale for providing alternative exercise options for this population. PROSPERO Registration No.: CRD42021254581.

Provision of exercise services in patients with peripheral artery disease in the United Kingdom.

OBJECTIVES: Supervised exercise programmes (SEPs) are a vital treatment for people with intermittent claudication, leading improvements in walking distance and quality of life and are recommended in multiple national and international guidelines. We aimed to evaluate the use and structure of SEPs in the United Kingdom (UK). DESIGN: We conducted an anonymous online survey using the Jisc platform comprising of 40 questions. The survey was designed to address key areas such as access, provision, uptake and delivery of SEPs in the United Kingdom. Ethical approval was obtained from Coventry University (P108729). METHODS: The list of trusts providing vascular services was obtained from the National Vascular Registry (NVR) report. The survey was disseminated via social media, The Vascular Society of Great Britain and Ireland and the Society for Vascular Technology. Data were exported to a Microsoft Excel document and analysed using simple descriptive statistics. RESULTS: Of 93 vascular units identified, we received response from 48. Of these, 23 had access to an exercise programme (48%). The majority of SEPs were exclusively for PAD patients (77%), with 21% using integrated services. 67% of respondents were providing a circuit-based programme, and 5 out of 23 were meeting the dose recommendations in the UK National Institute for Health and Care Excellence (NICE) guidelines. Respondents felt that programmes were moderately to extremely important to patients, slightly to very important to clinicians and not at all important to slightly important to commissioning/funding bodies. CONCLUSION: SEPs are a well-established first-line treatment for patients with IC and they are recommended by NICE guidelines. Despite this, many patients still do not have access to an exercise programme, and clinicians do not feel that they have support from commissioning/funding bodies to develop them. There is an urgent need for funding, development and delivery of SEPs in the United Kingdom.

A Systematic Review of Exercise Prescription in Patients with Intermittent Claudication: Does Pain Matter?

BACKGROUND: Current guidelines for intermittent claudication advocate exercise at moderate to maximal claudication pain. However, adherence rates to supervised exercise programmes (SEP) remain poor and claudication pain is a contributing factor. Limited evidence suggests that moderate or pain-free exercise may be just as beneficial and may be better tolerated. However, it remains unclear what 'level' of claudication pain is optimal for improving functional outcomes. We therefore conducted a systematic review to synthesise the evidence for exercise prescribed at different levels of claudication pain. METHODS: The CENTRAL, MEDLINE, Embase and CINAHL databases were searched up to October 2020. Randomized controlled trials (RCTs) that directly compared at least 2 different intensities of claudication pain were included. Outcome measures included walking performance, adherence, quality of life and vascular function. RESULTS: Of 1,543 search results, 2 studies were included. Maximal walking distance improved by 100-128% in the moderate-pain SEP groups, and by 77-90% in the pain-free SEP groups. Importantly, there were no significant differences between the moderate-pain and pain-free SEP groups in either study for improvements in walking performance, though comparison to a maximal-pain SEP group was not made. CONCLUSIONS: The efficacy of SEPs for patients with intermittent claudication is irrefutable, though there is no consensus on the optimal level of pain. Therefore, adequately powered RCTs are required to compare the effect of pain-free SEPs, moderate-pain SEPs and maximal-pain SEPs on functional outcomes. (PROSPERO ID: CRD42020213684).

High-intensity interval training in cardiac rehabilitation: a multi-centre randomized controlled trial.

BACKGROUND: There is a lack of international consensus regarding the prescription of high-intensity interval training (HIIT) for people with coronary artery disease (CAD) attending cardiac rehabilitation (CR). AIMS: To assess the clinical effectiveness and safety of low-volume HIIT compared with moderate-intensity steady-state (MISS) exercise training for people with CAD. METHODS AND RESULTS: We conducted a multi-centre RCT, recruiting 382 patients from 6 outpatient CR centres. Participants were randomized to twice-weekly HIIT (n = 187) or MISS (n = 195) for 8 weeks. HIIT consisted of 10 × 1 min intervals of vigorous exercise (>85% maximum capacity) interspersed with 1 min periods of recovery. MISS was 20-40 min of moderate-intensity continuous exercise (60-80% maximum capacity). The primary outcome was the change in cardiorespiratory fitness [peak oxygen uptake (VO2 peak)] at 8 week follow-up. Secondary outcomes included cardiovascular disease risk markers, cardiac structure and function, adverse events, and health-related quality of life. At 8 weeks, VO2peak improved more with HIIT (2.37 mL.kg-1.min-1; SD, 3.11) compared with MISS (1.32 mL.kg-1.min-1; SD, 2.66). After adjusting for age, sex, and study site, the difference between arms was 1.04 mL.kg-1.min-1 (95% CI, 0.38 to 1.69; P = 0.002). Only one serious adverse event was possibly related to HIIT. CONCLUSIONS: In stable CAD, low-volume HIIT improved cardiorespiratory fitness more than MISS by a clinically meaningful margin. Low-volume HIIT is a safe, well-tolerated, and clinically effective intervention that produces short-term improvement in cardiorespiratory fitness. It should be considered by all CR programmes as an adjunct or alternative to MISS. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02784873. https://clinicaltrials.gov/ct2/show/NCT02784873.

Cardiac rehabilitation exercise training can improve cardiorespiratory fitness and quality of life for people with coronary artery disease, but sometimes, it is not effective. The intensity of the exercise training may be important. We conducted a randomized controlled trial to test if moderate-intensity exercise or high-intensity exercise was better.High-intensity interval training was more effective than moderate-intensity exercise training for improving cardiorespiratory fitness in people with coronary artery disease attending cardiac rehabilitation.High-intensity interval training was safe and well tolerated.

Effects of exercise prescribed at different levels of claudication pain on walking performance in patients with intermittent claudication: a protocol for a randomised controlled trial.

BACKGROUND: Peripheral artery disease affects over 236 million people globally and the classic symptom is intermittent claudication (IC) which is associated with reduction in physical activity. The evidence that supervised exercise programmes (SEPs) improve pain-free and maximal walking distance is irrefutable. However, adherence rates are low with exercise-related pain cited as a contributing factor. National and international guidelines recommend exercising at a moderate to maximal level of claudication pain to improve walking ability; however, exercising pain-free or at mild claudication pain has been shown to achieve this outcome. There is limited evidence that compares the relative effects of exercise prescribed at different levels of claudication pain. OBJECTIVE: The objective of this study is to directly compare the effects of exercise prescribed at three different levels of claudication pain on walking performance. DESIGN: This study will be a single-centre randomised controlled trial. METHODS: Based on an a priori power calculation, 51 patients with IC will be allocated to 24 weeks of twice-weekly pain-free (PF), moderate pain (MOD-P) or maximal pain (MAX-P) exercise. The PF group will cease exercise at the onset of claudication (1 on the 0-4 IC rating scale), the MOD-P group will stop once moderate pain is reached (2 on the rating scale) and the MAX-P group will stop once maximal pain is reached (4 on the rating scale). ANALYSIS: Outcome measures will be assessed at baseline, 12 and 24 weeks adopting an analysis of covariance (ANCOVA) to compare MWD across three time points. The primary outcome for the trial will be change in maximal treadmill walking distance at 12 and 24 weeks. REGISTRATION: Trial registration number: NCT04370327.

A systematic review of exercise testing in patients with intermittent claudication: A focus on test standardisation and reporting quality in randomised controlled trials of exercise interventions.

A systematic review was conducted to identify the range of terminology used in studies to describe maximum walking distance and the exercise testing protocols, and testing modalities used to measure it in patients with intermittent claudication. A secondary aim was to assess the implementation and reporting of the exercise testing protocols. CINAHL, Medline, EMBASE and Cochrane CENTRAL databases were searched. Randomised controlled trials whereby patients with intermittent claudication were randomised to an exercise intervention were included. The terminology used to describe maximal walking distance was recorded, as was the modality and protocol used to measure it. The implementation and reporting quality was also assessed using pre-specified criteria. Sixty-four trials were included in this review. Maximal walking distance was reported using fourteen different terminologies. Twenty-two different treadmill protocols and three different corridor tests were employed to assess maximal walking distance. No single trial satisfied all the implementation and reporting criteria for an exercise testing protocol. Evidence shows that between-study interpretation is difficult given the heterogenous nature of the exercise testing protocols, test endpoints and terminology used to describe maximal walking distance. This is further compounded by poor test reporting and implementation across studies. Comprehensive guidelines need to be provided to enable a standardised approach to exercise testing in patients with intermittent claudication.

Oxygen Costs of the Incremental Shuttle Walk Test in Cardiac Rehabilitation Participants: An Historical and Contemporary Analysis.

BACKGROUND: The incremental shuttle walk test (ISWT) is a standardised assessment for cardiac rehabilitation. Three studies have reported oxygen costs (VO2)/metabolic equivalents (METs) of the ISWT. In spite of classic representations from these studies graphically showing curvilinear VO2 responses to incremented walking speeds, linear regression techniques (also used by the American College of Sports Medicine [ACSM]) have been used to estimate VO2. PURPOSE: The two main aims of this study were to (i) resolve currently reported discrepancies in the ISWT VO2-walking speed relationship, and (ii) derive an appropriate VO2 versus walking speed regression equation. METHODS: VO2 was measured continuously during an ISWT in 32 coronary heart disease [cardiac] rehabilitation (CHD-CR) participants and 30 age-matched controls. RESULTS: Both CHD-CR and control group VO2 responses were curvilinear in nature. For CHD-CR VO2 = 4.4e0.23 × walkingspeed (km/h). The integrated area under the curve (iAUC) VO2 across nine ISWT stages was greater in the CHD-CR group versus the control group (p < 0.001): CHD-CR = 423 (±86) ml·kg-1·min-1·km·h-1; control = 316 (±52) ml·kg-1·min-1·km·h-1. CONCLUSIONS: CHD-CR group vs. control VO2 was up to 30 % greater at higher ISWT stages. The curvilinear nature of VO2 responses during the ISWT concur with classic studies reported over 100 years. VO2 estimates for walking using linear regression models (including the ACSM) clearly underestimate values in healthy and CHD-CR participants, and this study provides a resolution to this when the ISWT is used for CHD-CR populations.