Effect of High‐Intensity Interval Training and Moderate‐Intensity Continuous Training in People With Poststroke Gait Dysfunction: A Randomized Clinical Trial

Abstract

Background

The exercise strategy that yields the greatest improvement in both cardiorespiratory fitness ($\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$) and walking capacity poststroke has not been determined. This study aimed to determine whether conventional moderate‐intensity continuous training (MICT) or high‐intensity interval training (HIIT) have different effects on $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ and 6‐minute walk distance (6MWD).

Methods and Results

In this 24‐week superiority trial, people with poststroke gait dysfunction were randomized to MICT (5 days/week) or HIIT (3 days/week with 2 days/week of MICT). MICT trained to target intensity at the ventilatory anaerobic threshold. HIIT trained at the maximal tolerable treadmill speed/grade using a novel program of 2 work‐to‐recovery protocols: 30:60 and 120:180 seconds. V̇O₂ and heart rate was measured during performance of the exercise that was prescribed at 8 and 24 weeks for treatment fidelity. Main outcomes were change in $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ and 6MWD. Assessors were blinded to the treatment group for $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ but not 6MWD. Secondary outcomes were change in ventilatory anaerobic threshold, cognition, gait‐economy, 10‐meter gait‐velocity, balance, stair‐climb performance, strength, and quality‐of‐life. Among 47 participants randomized to either MICT (n=23) or HIIT (n=24) (mean age, 62±11 years; 81% men), 96% completed training. In intention‐to‐treat analysis, change in $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ for MICT versus HIIT was 2.4±2.7 versus 5.7±3.1 mL·kg⁻¹·min⁻¹ (mean difference, 3.2 [95% CI, 1.5–4.8]; P<0.001), and change in 6MWD was 70.9±44.3 versus 83.4±53.6 m (mean difference, 12.5 [95% CI, −17 to 42]; P=0.401). HIIT had greater improvement in ventilatory anaerobic threshold (mean difference, 2.07 mL·kg⁻¹·min⁻¹ [95% CI, 0.59–3.6]; P=0.008). No other between‐group differences were observed. During V̇O₂ monitoring at 8 and 24 weeks, MICT reached 84±14% to 87±18% of $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ while HIIT reached 101±22% to 112±14% of $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ (during peak bouts).

Conclusions

HIIT resulted in more than a 2‐fold greater and clinically important change in $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ than MICT. Training to target (ventilatory anaerobic threshold) during MICT resulted in ~3 times the minimal clinically important difference in 6MWD, which was similar to HIIT. These findings show proof of concept that HIIT yields greater improvements in cardiorespiratory fitness than conventional MICT in appropriately screened individuals.

Registration

URL: https://www.clinicaltrials.gov; Unique identifier: NCT03006731.

Nonstandard Abbreviations and Acronyms

$\dot{\mathbf{V}}{\mathbf{O}}_{\mathbf{2}\mathbf{VT}\mathbf{1}}$

ventilatory anaerobic threshold

6MWD

6‐minute walk distance

AE

adverse events

CPET

cardiopulmonary exercise stress test

$\mathbf{CRF}/\dot{\mathbf{V}}{\mathbf{O}}_{\mathbf{2}\mathbf{\text{peak}}}$

cardiorespiratory fitness/peak oxygen uptake

HIIT

high‐intensity interval training

MICT

moderate‐intensity continuous training

Clinical Perspective.

What Is New?

• There is a lack of stroke trials that directly compare the effect of different exercise intensities or use of a combination of high‐intensity interval training (HIIT) parameters on cardiorespiratory fitness and walking capacity.

• Six months of a novel HIIT protocol using shorter (30 seconds) and longer (120 seconds) high‐intensity intervals resulted in more than a 2‐fold significant and clinically important greater change in $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ compared with conventional moderate‐intensity continuous training at the ventilatory anaerobic threshold.

• Both groups had similar and marked increases in 6‐minute walk distance (>70 m). HIIT was safe, and adherence was high.

What Are the Clinical Implications?

• Structured exercise (either moderate‐intensity continuous training or HIIT) improved walking capacity, but HIIT had a larger, clinically important, impact on cardiorespiratory fitness.

• This is important given the association between $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ and mortality.

• These findings show proof of concept that HIIT yields greater improvements in cardiorespiratory fitness than conventional moderate‐intensity continuous training in appropriately screened individuals.

While aerobic exercise training benefits individuals recovering from stroke, ¹ there is insufficient evidence to inform optimal exercise intensity and training strategies to improve both cardiorespiratory fitness (CRF) and walking capacity. Currently, the recommendations from health organizations are to prescribe moderate‐intensity continuous training (MICT), downgrading recommendations for high‐intensity exercise based on the lack of stroke trials conducted that directly compare different intensities of exercise and high‐intensity interval training (HIIT) parameters (ie, work to rest intervals). ¹ , ² , ³

Deconditioning and incomplete recovery of walking speed and endurance are common poststroke and pose barriers to returning to regular activities‐of‐daily‐living for most individuals. ⁴ , ⁵ Determining strategies to optimize CRF is also important as low CRF may be associated with higher stroke risk ⁶ and is a strong independent predictor of cardiovascular and all‐cause mortality. ⁷ , ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³

Most studies have used conventional training models of MICT. This model increases CRF but is typically not adequate to meet the threshold required to complete many activities of daily living. ¹⁴ , ¹⁵ Greater gains in CRF and walking capacity may be possible with high‐intensity exercise. ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ Yet, it is challenging for people poststroke to maintain high intensities for an adequate duration owing to disability, fatigue, and poor balance. ²⁰ In a prior study, we noted that 72% (43 of 60) of people with poststroke gait dysfunction were unable to reach a walking intensity at or above the recommended intensity for improving CRF (ie, the ventilatory anaerobic threshold) during a 6‐minute walk distance (6MWD) assessment, owing predominantly to poor balance. ²⁰ However, preliminary studies suggest that the barriers to high‐intensity exercise can be overcome with shorter overall durations (~20 minutes) that include brief bursts of high‐intensity activity followed by intervals of low‐intensity exercise. ²¹ , ²² , ²³ , ²⁴ This high‐intensity interval training (HIIT) strategy allows a greater amount of work at a higher intensity relative to energy‐expenditure‐matched MICT. ²⁵

Studies that randomized people poststroke to HIIT versus MICT training in stroke have focused on HIIT protocols targeted at gait retraining for improving walking capacity/locomotor function, not on protocols targeting CRF or both. These studies have used interventions that elicit minimal aerobic stimuli using short work intervals of 10 seconds ²¹ , ²² or 30 seconds ²⁶ and some combined with long rest periods of 120 seconds ²¹ or until the heart rate (HR) returns to resting levels. ²² In addition, the comparison MICT groups have not been trained to optimal target exercise intensity (ventilatory anaerobic threshold) but at a percentage of the peak intensity attained on an exercise stress test, which is often submaximal. ²⁷ Indeed, while a shorter duration high‐intensity interval allows for faster treadmill speeds and large motor unit recruitment, it takes longer than 30 seconds of high‐intensity exercise to increase cardiac stroke volume and reach $\dot{\mathrm{V}}{\mathrm{O}}_{2\max }$. ²⁸ , ²⁹

No study has used a strategy of combining longer and shorter high‐intensity intervals that targets CRF and walking capacity or trained the MICT group to target intensity levels in people poststroke. Therefore, the primary objective of this study was to investigate whether 24 weeks of this novel HIIT strategy is superior to conventional MICT training at improving CRF and 6MWD in people following stroke with gait dysfunction. We hypothesized that HIIT would result in significantly greater improvements in CRF. In addition, despite there being only a low to moderate correlation between 6MWD and CRF, ³⁰ we hypothesized that HIIT would result in greater walking capacity than MICT given the combination of HIIT work‐to‐rest protocols.

METHODS

Study Design

This was a 24‐week 2‐arm parallel‐group superiority trial comparing a HIIT exercise protocol to a conventional MICT protocol from March 2017 to July 2022 in Toronto, Canada. The study coordinator enrolled participants into the trial. Participants were randomly assigned to MICT or HIIT in a 1:1 ratio by a researcher uninvolved in the study through the use of sealed opaque envelopes containing group assignment after each baseline cardiopulmonary exercise stress test (CPET). The irreversible group assignment was revealed to the participant by the study coordinator. Assessors were blinded to treatment groups for evaluation of CRF but not 6MWD or secondary outcome measures. The study followed the CONSORT statement on randomized trials. The protocol is available in Data S1. The data that support the findings of this study are available from the corresponding author upon reasonable request. The study was approved by the University Health Network's Research Ethics Board. All participants provided written informed consent. The trial was registered at ClinicalTrials.gov (NCT03006731).

Participants and Setting

Consecutively referred participants from outpatient stroke rehabilitation programs, primary care, and stroke specialists to Toronto Rehab's Cardiovascular Prevention and Rehabilitation program were approached for study recruitment. Inclusion criteria: (1) a clinical diagnosis of stroke (hemorrhagic or ischemic); (2) ≥10 weeks poststroke; (3) ability to walk at least 100 m with or without an assistive device with no severe limitations but with a hemiparetic gait pattern (<7 on the Chedoke‐McMaster Stroke Assessment scale ³¹ of the leg or foot); (4) no severe communicative, cognitive, or behavioral issues limiting exercise testing and training. Exclusion criteria: (1) orthopedic issues aggravated by exercise, (2) contraindications to a CPET ³ and other morbidities that would limit exercise tolerance (eg, unstable angina, symptomatic aortic stenosis).

Descriptive Measures

Demographics, including age, sex, self‐reported race/ethnic origins, country of birth, annual household income, anthropometrics, medical history, and medications, were recorded. The medical outcomes study social support survey and the Centre for Epidemiological Studies Depression scale (CES‐D) questionnaire were administered at baseline. ³² , ³³ A requisition for a fasting blood test was issued to each participant at baseline to be conducted at a lab of the participant's choice.

Intervention

Both groups participated in overground MICT (5 sessions/week) during the first 4 weeks of the study. Resistance training was initiated on the second visit and completed at each of the 3 weekly supervised sessions by all participants. This initial period provided a foundation of fitness, endurance, and strength for the safe prescription of HIIT. For the subsequent 20 weeks, the HIIT group replaced 3 MICT sessions with 3 HIIT sessions per week, and MICT continued with 5 MICT sessions per week (Figure 1). Both groups exercised mostly on a treadmill with a harness secured to an overhead support system for fall protection and used handrail support. One to 2 times/month, participants completed supervised exercise overground (including the HIIT prescription) to facilitate transition to the community. The HIIT protocol consisted of 3 HIIT sessions/week combined with 2 MICT sessions/week; the MICT protocol consisted of 5 sessions/week. Sessions were supervised except for 2 MICT sessions/week that were conducted at home by all participants. A community walking route was mapped out for each participant. HR was monitored in all participants during supervised sessions using Polar® (A300) HR monitors. The unsupervised exercise was tracked via an exercise log reviewed weekly.

Figure 1. Flow diagram of study procedures.

HIIT indicates high‐intensity interval training; and MICT, moderate‐intensity continuous training.

MICT (Both Groups)

The training intensity was based on a CPET conducted at baseline and 12 weeks. The goal was to progress participants to a maximum of 60 minutes of exercise at the treadmill workload or HR corresponding to the V̇O₂ that occurred at the ventilatory anaerobic threshold ($\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$). $\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$ is recommended as the gold standard target intensity level for exercise prescription in those with cardiovascular disease. ³⁴ If there was no discernible $\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$, a combination of the following was used: 60% to 80% of HR reserve or $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ mL∙kg⁻¹∙min⁻¹ and a rating of perceived exertion of 12 to 16 on the Borg 6 to 20 Scale (somewhat hard to hard). The initial walking prescription was set at a distance of up to 1.6 km depending on exercise tolerance, with a 3‐minute warm‐up and cool‐down at 1.2 minutes/km slower than the prescription pace. Prescriptions progressed approximately every 2 weeks, increasing the distance first, then increasing intensity, then distance again. Prescription target levels were adjusted based on the results of the 12‐week CPET. The 12‐week CPET was used for exercise prescription and treatment fidelity as described below. Exercise diary information, HR, and communication with the participant were considered when increasing the prescription.

High‐Intensity Interval Training

In the first 4 weeks of HIIT training (ie, weeks 5–8), only HIIT workout #1 was prescribed (3 sessions/week). Thereafter, workout #1 was reduced to 1 session/week, and workout #2 was carried out 2 sessions/week. HIIT Workout #1: Participants were prescribed 30 seconds of maximal safe intensity alternating with 60 seconds of active recovery ³⁵ (~30%–40% of peak HR attained on the CPET or rating of perceived exertion of 10–12 [“light”]) (Table S1). Starting with 3 HIIT intervals, an increasing number of intervals was prescribed so that after 4 weeks, all 15 HIIT intervals were completed. HIIT Workout # 2: Four weeks after Workout #1 was initiated, intervals of 2 minutes of maximal safe intensity alternating with 3 minutes of active recovery were prescribed. Each HIIT workout was approximately 20 to 22 minutes with additional 5‐minute warm‐up and cool‐down periods. The first high‐intensity interval of each workout included a gradual ramp‐up to target intensity. To determine HIIT intensity, the treadmill speed was ramped up every 5 seconds until a maximal tolerable safe speed was attained (terminated when drifting to the distal end of the treadmill or gait instability). Following a brief rest and starting at the previously determined maximal speed, the incline gradually increased until a maximal tolerable grade was reached. The ability to sustain this intensity at shorter and longer intervals was then assessed, and the speed/grade was adjusted as necessary. A combination of the following also guided the intensity: rating of perceived exertion of ≥17 (very hard) ¹ , ³⁶ , ³⁷ ; the workload or HR that occurred at ≥91% of $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ on the CPET; and the HR/workload above the $\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$. ³ The treadmill speed and incline were reassessed every 3 weeks and then readjusted based on the results of the 12‐week CPET.

Acute Measures of Exercise Parameters (Treatment Fidelity)

HR and V̇O₂ were measured at 2 time points on a calibrated treadmill to assess whether target training intensity levels were attained. The first was conducted at 8 weeks (after 4 weeks of HIIT training), carrying out the most recently prescribed 30‐second HIIT prescription and, for MICT, carrying out the most recent MICT prescription. The second was conducted after 24 weeks during the 30‐second and 2‐minute HIIT prescription (on separate days) and the most recent MICT prescription for the MICT group. HR and V̇O₂ at 8 and 24 weeks were reported as absolute measures and relative to the baseline and 12‐week CPET, respectively (ie, $\%\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$, %HR reserve, etc), to demonstrate treatment fidelity and appropriate exercise progression based on the most recent training intensity targets. The resting HR at the time of monitoring was used to calculate the % HR reserve. HR was measured using a Polar HR monitor. V̇O₂ was measured using an ambulatory oxygen monitor (CORTEX Biophysik MetaMax 3X portable gas analyzer, Germany). ³⁸ , ³⁹ This technology allows for reliable and accurate measures of oxygen uptake in stroke participants. ⁴⁰ Event markers were recorded, including those at each HIIT interval.

Adverse Event Monitoring

Grading and categorization of adverse events (AEs) were conducted using the Common Terminology Criteria for Adverse Events. ⁴¹ Participants were queried about adverse events at each study visit.

Primary Outcome Measures

Cardiorespiratory Fitness

A CPET was performed at baseline and 24 weeks on a treadmill using the “Ramp Protocol” ⁴² by 2 cardiopulmonary exercise stress test technologists and a staff physician unrelated to the research study and blinded to study group assignment. A harness secured to an overhead support system for fall protection was used. Treadmill handrail support was standardized, and a glove to secure the hemiparetic hand to the handrail was used as appropriate. At baseline and on a day before the CPET, a 12‐lead ECG and physical assessment was conducted by a staff physician, followed by a familiarization session on the treadmill. Maximal tolerated grade and gait speed were assessed to determine the starting speed and maximal grade increment on the CPET to facilitate reaching a “true” physiological maximum. ⁴³ Breath‐by‐breath gas samples were collected and averaged over 20 seconds via a calibrated metabolic cart (SensorMedics Vmax Encore, CA) to determine $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ (mL∙kg⁻¹∙min⁻¹). ECG and blood pressure were monitored throughout. Indications for discontinuing the CPET were peak volitional effort or the appearance of adverse clinical signs or symptoms as described elsewhere. ³ The expected $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ was calculated from established norms ⁴⁴ for comparison across age, sex, height, and body mass. $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ during symptom‐limited exercise stress testing is demonstrated to have very high test–retest reliability (r>0.91) in people poststroke. ⁴⁵ , ⁴⁶

Six‐Minute Walk Distance Testing

Walking capacity was measured by 6MWD. ⁴⁷ The 6MWD measures the distance that an individual can quickly walk in a period of 6 minutes on a flat surface. The test was performed at baseline and 24 weeks on a 30‐m course and standardized according to guidelines. ⁴⁷ Standardized instructions were given to cover as great a distance as possible during the allotted time. Participants used the same gait aid, if prescribed, on all tests. Norms based on height, body mass, and sex were reported. ⁴⁸ The 6MWD test has excellent test–retest reliability and adequate interrater reliability. ⁴⁶ , ⁴⁹ , ⁵⁰

Secondary Outcomes

All secondary outcomes were conducted at baseline and 24 weeks.

VO₂ at the Ventilatory Anaerobic Threshold

The $\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$ is considered a valid measure demonstrating high interrater reliability in the stroke population. ⁵¹ $\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$ was determined by a combination of the V‐slope method and the ventilatory equivalents methods ⁵² by 2 independent assessors. ²⁷ , ⁵³ The V‐slope method is defined as the point of departure from linearity of CO₂ output plotted against VO₂. The ventilatory equivalent method is defined as the level corresponding to the rise in the ventilatory equivalent of VO₂ that occurs when the ventilatory equivalent of CO₂ remains relatively constant.

Ten‐M Fast Walk Speed

Two 10‐m timed walks at maximal comfortable speed were conducted at each time point. To avoid measuring acceleration and deceleration, participants started 2 m before and ended 2 m after the 10‐m distance. The faster of 2 timed trials was recorded. We also conducted a dual‐task gait assessment by having participants perform the 10‐m fast walk, first while counting backwards by 3s starting from 50 or 70 (counterbalanced order based on other assessments) and then while naming words beginning with F or B (counterbalanced order based on other assessments). These cognitive measures have clinical relevance as there is likely a shared pathology underlying motor (specifically gait speed) and cognitive function related to the domain of executive function/response inhibition. ⁵⁴ , ⁵⁵

Gait Economy

Gait economy was assessed by measuring V̇O₂ using the previously described oxygen uptake monitor during 4‐minutes of steady state treadmill exercise at the workload that occurred at the $\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$ on the baseline CPET. If there was no discernable $\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$, the workload at 70% of $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ was used. Ten‐second sampling was used, and 2 independent assessors determined the mean V̇O₂ over a 1‐minute period where steady state exercise was achieved. The final metric was the average from the 2 assessors if their values were within <10%; otherwise, they were resolved by consensus.

Cognition

Domains of attention and executive function have been shown to benefit most from an exercise intervention. ⁵⁶ Moreover, impairments in executive function, attention, and memory are prevalent in up to 78% of people poststroke. ⁵⁷ Therefore, we administered the Stroop test, ⁵⁸ Trail Making Test A and B, Delis‐Kaplan Executive Function System (D‐KEFS) verbal fluency (letters FAS at baseline and BHR at 24 weeks), and the Wechsler Digit Symbol Coding assessment. The Erickson spatial matching task ⁵⁹ was included as a spatial working memory task. The Montreal Cognitive Assessment was also administered (counterbalanced order of 2 versions). The Montreal Cognitive Assessment score for B or F was used for D‐KEFS if done at the same time point.

Berg Balance

A validated 14‐item scale measuring balance was used, ⁶⁰ with a maximum score of 56 and higher scores indicating better balance.

Stair Climb

This was measured as the time to ascend 20 stairs as quickly as possible. Railing support was standardized. Participants started at the base of a 20‐step flight of stairs adjacent to the handrail of their nonaffected upper limb. They were instructed by the examiner to use the handrail as they ascended the stairs safely and as fast as possible. The subject started when the examiner said, “Go.” When the subject had both feet planted on the top step, the timing stopped. This assessment has been used in people following stroke, demonstrating associations of paretic lower extremity muscle strength/torque and standing balance with stair‐climbing ability. ⁶¹ , ⁶²

Muscular Strength

The 1 repetition maximum (1RM) test was performed for a bicep curl, leg curl, and leg extension exercises on affected and nonaffected sides separately. After 3 repetitions of a warm‐up weight (previously determined to elicit an rating of perceived exertion of 13 to 15, somewhat hard to hard, on the last of 10 repetitions), a slightly heavier weight was attempted once following a 2‐minute rest period. ⁶³ One repetition at a heavier weight was attempted every 2 minutes until the participant was unable to lift the weight with proper technique.

Quality‐of‐Life

The Stroke Impact Scale version 2.0 and the Medical Outcomes Study, 12‐item Short Form Health Domain Survey, was used to measure quality‐of‐life. ⁶⁴ , ⁶⁵

Step Activity Monitoring

Participants wore PiezoRx devices (Bluetooth enabled) for 48 hours pre‐ and poststudy. This device accurately measures steps at slower speeds and in a variety of body types. ⁶⁶

Statistical Analysis

An intent‐to‐treat approach was conducted for the primary outcomes. Only participants with complete pre‐ and postmeasures were included in a sensitivity analysis. A complete case analysis was conducted for secondary outcomes. Between‐group differences were analyzed using ANCOVA, with baseline measures as covariates (see Data S1 for a summary of the change in the protocol). ⁶⁷ The secondary outcome measures were tested using the same statistic, with false discovery rate correction to the P value ⁶⁸ for both primary and secondary outcome measures to control for type I error. To account for missing at random data at the 24‐week time point, a single imputation approach (expectation–maximization method) was conducted. ⁶⁹ , ⁷⁰ Bivariate analysis using χ ² or Fisher exact test for proportions as appropriate was used to compare the proportion of participants who had ≥1 AE between HIIT versus MICT. Analysis of Acute V̇O ₂ Measures for Treatment Fidelity: Paired t‐tests were used to measure within‐group changes. Mean time spent at critical intensities was not normally distributed and thus analyzed using Mann–Whitney U tests for independent samples and Wilcoxon signed‐ranks test for related samples. All analyses were performed in SPSS (v28.0; IBM Corp, Armonk, NY).

Sample Size

A target sample of 21 participants per group with an additional 4 participants to account for attrition was originally estimated to be powered to show a clinically relevant between‐group difference in CRF of 2.5 mL∙kg⁻¹∙min⁻¹ (SD of ±2.5), associated with a 23% to 37.5% reduction in mortality in those with coronary heart disease. ⁷ , ¹⁰ , ¹¹ , ¹³ Please see Data S1 for a summary of the change in protocol where a target sample size of 42 participants per group with an additional 10 participants to account for attrition was estimated to provide sufficient conjunctive power to detect a clinically meaningful difference of 30±45 m in 6MWD. Enrollment was discontinued before reaching this target sample owing to restrictions on research activities associated with the COVID‐19 pandemic that protracted recruitment. This decision was made before the analysis of outcome data. However, the between‐group difference in CRF was much larger, and there was lower attrition than the original estimate than in the current sample.

RESULTS

Of the 95 participants screened, 47 were enrolled in the study (Figure 2). Of those enrolled, 24 were randomized to HIIT and 23 to MICT. All patients received the intended treatment to which they were randomized. Baseline characteristics were similar between HIIT and MICT groups (Table 1). Overall, 96% completed the study (HIIT; n=23 and MICT; n=22). One participant (HIIT group) completed the final CPET without gas analysis owing to a fall at home (unrelated to the intervention). Only 6% and 8.5% of the 24‐week $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ and 6MWD data were missing, respectively, and Little's test ⁷⁰ , ⁷¹ indicated that the data were missing completely at random (P=0.341 and P=0.507, respectively).

Figure 2. Consort flow diagram.

COPD indicates chronic obstructive pulmonary disease; CPET, cardiopulmonary exercise stress test; ESL, English as second language; HIIT, high‐intensity interval training; ICD, implanted cardioverter‐defibrillator; MICT, moderate‐intensity continuous training; and PAD, peripheral artery disease.

Table 1.

Baseline Demographic and Clinical Characteristics of Participants and Adherence to the Intervention

Characteristics	HIIT [n=24]	MICT [n=23]
Sociodemographic
Age, y (min‐max)	62.8±13.2 (34–85)	60.9±8.4 (38–77)
Sex, men, n (%)	20 (83)	18 (78)
Partnered, n (%)	19 (79)	14 (61)
Race (self‐reported), Asian/Black/Hispanic Latinx/White, n (%)	8 (33)/3 (13)/0/13 (54)	8 (35)/2 (9)/2 (9)/11 (48)
Country of birth, (Canada/other), n (%)	8 (33)/16 (67)	7 (30)/16 (70)
Annual household income, <50 000/≥50 000 CAD, n (%) [No. respondents]	7 (32)/15 (68) [22]	7 (41)/10 (59) [17]
MOS social support, median score (IQR)	4.2 (1.0)	4.7 (1.9)
CES‐D depression, median score (IQR)	8.0 (11) [23]	13 (14.8) [20]
Smoking, current/quit/never, n (%)	1 (4)/10 (42)/13 (54)	2 (9)/8 (35)/13 (57)
Clinical characteristics
Body mass index, kg∙m2	25.6±4.7	26.5±4.3
Waist circumference, cm	90.8±11.6	95.7±13.3
Resting heart rate, bts∙min−1	76.6±13.7	77.3±11.6
Resting systolic blood pressure, mm Hg	124.5±14.9	122.0±13.1
Resting diastolic blood pressure, mm Hg	74.7±8.8	73.6±8.0
Fasting glucose, median mmol/L (IQR) [n tested]	6.0 (1.6)	5.8 (2.4) [22]
Fasting A1c, median % (IQR)	5.8 (1.2)	5.9 (2.3) [22]
Fasting total cholesterol	3.37±0.84	3.89±0.98 [22]
Fasting HDL cholesterol, mmol/L	1.24±0.40	1.29±0.42 [22]
Fasting LDL cholesterol, mmol/L	1.63±0.62	1.94±0.79 [22]
Fasting triglycerides, mmol/L	1.10±0.46	1.32±0.60 [22]
Stroke
Time poststroke, median months (IQR), min‐max	10.8 (7.3), 3.4–37.5	10.6 (9.5), 4.6–47.3
<6 months poststoke, n (%)	3 (13)	2 (9)
Ischemic/hemorrhagic stroke type, n (%)	16 (67)/8 (33)	20 (87)/3 (13)
Right/left/bilateral hemisphere affected, n (%)	11 (46)/10 (42)/3 (13)	7 (30)/12 (52)/4 (17)
Gait aids: none/SPC/quad cane/rollator, n (%)	11 (46)/3 (13)/3 (13)/7 (29)	3 (13)/7 (30)/3 (13)/10 (44)
CMSA median score (IQR), min‐max
Leg	4.0 (3), 2–6	4.0 (1), 3–6
Foot	4.0 (2), 2–7	3.0 (2), 1–7
MoCA score<25, n (%)	12 (50)	15 (65)
Comorbid conditions, n (%)
Hypertension	20 (83)	20 (87)
Diabetes	12 (57)	9 (43)
Coronary artery disease	6 (25)	4 (17)
Sleep apnea	6 (25)	3 (13)
Chronic obstructive pulmonary disease	1 (4)	1 (4)
Atrial fibrillation, (history, not current rhythm)	2 (8)	2 (9)
Peripheral artery disease	2 (8)	0
Hypothyroidism (history)	2 (8)	1 (4)
Cancer (history)	2 (8)	0
$\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$, mL∙kg−1∙min−1	18.3±5.0	17.4±4.2
Predicted norms (age, sex, height, body mass, exercise testing modality), %	60.5±15.3	59.3±16.8
6‐min walk distance, m	324.2±109.3	287.0±98.8
Predicted norms (age, sex, height, body mass), %	64.1±22.6	54.0±20.2
Baseline exercise prescription
Distance, km	1.57±0.70	1.31±0.66
Duration, min	25.2±6.2	24.3±8.8
Speed, km∙hr−1	3.49±1.2	3.15±1.13
Attendance/adherence to intervention for all participants including withdrawals, count (% of max)
Supervised sessions, (max of 72)	63.2±12 (87.7±16.6)	61.1±6.7 (84.9±9.3)*
Home AT sessions, (max of 48)	31.0±10.1 (64.5±21.1)	33.7±10.3 (70.1±21.4)†
Total AT sessions, (max of 120)	94.1±17.2 (78.4±14.3)	94.8±12.6 (79.0±10.5)‡
Medications, n (%)
Lipid‐lowering agents, statins	20 (83)	19 (83)
Beta blockers	8 (33)	5 (22)
Ca2+ channel antagonists	11 (46)	12 (52)
Other antihypertensives (diuretic, ARB, ACE)	17 (71)	16 (70)
Antidiabetic agents, any	12 (50)	9 (39)
Antidiabetic agent, insulin	3 (13)	2 (9)
Antidepressants	3 (13)	3 (13)

Values are mean (SD) unless otherwise indicated. $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ indicates peak oxygen uptake; A1c, hemoglobin A1c; ACE, angiotensin‐converting enzyme inhibitor; ARB, angiotensin II receptor blocker; AT, aerobic training; CAD, Canadian Dollars; CES‐D, Centre for Epidemiological Studies Depression Scale; CMSA, Chedoke‐McMaster Stroke Assessment Score; HDL, high‐density lipoprotein; HIIT, high‐intensity interval training; IQR, interquartile range; LDL, low‐density lipoprotein; MICT, moderate‐intensity continuous training; MoCA, Montreal Cognitive Assessment; MOS, Medical Outcomes Study; and SPC, single point cane.

^* P value=0.478.

^† P value=0.370.

^‡ P value=0.882 between groups for attendance/adherence data.

Primary Outcomes

Change in $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ after 24 weeks was significantly greater for HIIT (5.7±3.1 mL·kg⁻¹·min⁻¹) versus MICT (2.4±2.7 mL·kg⁻¹·min⁻¹), with a mean difference of 3.2 mL·kg⁻¹·min⁻¹ [95% CI, 1.5−4.8], P<0.001 and a large effect size (n² _P) of 0.212 (Table 2). This represents a relative change of 30±18% for HIIT and 13±15% for MICT. There was no significant difference in 6MWD change between HIIT (83.4±53.6 m) and MICT (70.9±44.3 m), with a mean difference of (12.5 m [95% CI, −17 to 42], P=0.401) and a small n² _P of 0.005.

Table 2.

Effects of Exercise Strategy on Primary and Secondary Outcomes

Variable [sample size]	Mean change from baseline to 24 weeks (SD) HIIT (n=24)	Mean change from baseline to 24 weeks (SD) MICT (n=23)	Adjusted mean difference in change between HIIT and MICT* [95%CI]	P value
Primary outcomes
$\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$, mL∙kg−1∙min−1	5.7±3.1	2.4±2.7	3.2 [1.5−4.8]	<0.001
6‐min walk distance, m	83.4±53.6	70.9±44.3	12.5 [−17 to 42]	0.401
Secondary measures
$\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$, mL∙kg−1∙min−1	4.80±1.63 [21]	2.69±2.83 [16]	2.07 [0.59–3.6]	0.008
Gait economy, V̇O2 (mL·kg−1·min−1)	−2.0±3.2 [20]	−1.8±2.9 [21]	0.392 [−2.0 to 1.2]	0.619
10‐meter walk test, fast speed, m∙s−1	0.304±0.3 [20]	0.171±0.18 [20]	−0.051 [−0.94 to 0.84]	0.909
Dual task gait velocity, m∙s−1 (3s)	0.25±0.29 [20]	0.139±0.25 [22]	0.111 [−0.06 to 0.28]	0.198
Dual task effect (single subtract dual 3s), m∙s−1	0.05±0.22	0.038±0.14	0.054 [−0.06 to 0.17]	0.353
Dual task correct response rate 3s, n/time	0.002±0.38	−0.020±0.30	0.071 [−0.12 to 0.26]	0.444
Dual task gait velocity (FAS), m∙s−1	0.25±0.31	0.158±0.19	0.082 [−0.08 to 0.25]	0.320
Dual task effect (single‐dual FAS), m∙s−1	0.253±0.31	0.019±0.14	0.066 [−0.06 to 0.2.0]	0.305
Dual task, correct response rate FAS, n/time	0.001±0.26	0.075±0.17	−0.024 [−0.16 to 0.11]	0.718
Berg balance, score	1.45±3.0 [20]	2.5±5.1 [22]	−0.184 [−2.6 to 2.3]	0.880
Stair climb, seconds	−3.7±4.3 [20]	0.36±10.9 [22]	−3.4 [−9 to 3]	0.263
Muscular strength, 1 RM, kg	[23]	[22]
Biceps curl, affected	1.4±1.4	1.9±1.8	−0.103 [−0.94 to 0.73]	0.805
Biceps curl, nonaffected	1.3±1.7	2.0±2.2	−0.248 [−1.4 to 0.90]	0.667
Knee extension, affected	9.1±12.1	7.9±11.6	3.4 [−3.8 to 10.6]	0.346
Knee extension, nonaffected	7.6±10.9	6.8±14.4	1.4 [−5.6 to 8.4]	0.697
Knee flexion, affected	7.1±5.7	7.2±4.6	−0.5 [−3.8 to 2.9]	0.789
Knee flexion, nonaffected	10.6±10.1	9.5±8.4	1.5 [−4.0 to 7.0]	0.585
Steps piezo, mean steps/day	−84.9±2226 [18]	457±1040 [17]	−0.008 [−0.13 to 0.11]†	0.898†
Quality‐of‐life
SF‐12	[17]	[17]
Physical summary score	3.1±5.9	0.61±8.9	2.09 [−2.0 to 6.2]	0.306
Mental summary score	1.1±10.6	3.3±11.2	−1.26 [−7.8 to 5.3]	0.697
Stroke impact scale	[18]	[18]
Strength	−0.28±19.5	4.4±25.7	−3.37 [−15.8 to 9.1]	0.585
Memory	−2.2±10.5	−3.0±12.1	0.788 [−7.1 to 8.6]	0.839
Mood	−0.52±7.5	−1.7±9.0	2.01 [−3.3 to 7.3]	0.445
Communication	4.0±14.3	2.5±7.9	−1.04 [−4.7 to 2.6]	0.559
ADL/IADL	2.1±6.8	0.79±8.0	0.772 [−4.1 to 5.6]	0.747
Community mobility	1.7±7.5	5.1±11.9	−1.68 [−7.7 to 4.3]	0.570
Affected hand function	0±19.0	−4.7±20.0	7.41 [−6.5 to 21.3]	0.284
Participation	9.5±20.3	−0.43±12.3	9.21 [−0.46 to 18.9]	0.061
Recovery, 0%–100%	8.2±12.2	7.1±15.1	0.95 [−7.8 to 9.7]	0.825
Cognition	[23]	[22]
MoCA, counterbalanced	0±1.5	1.0±3.1	−0.71 [−2.3 to 0.83]	0.358
Trail making test A, s	1.4±18.0	−9.6±43.9	12.9 [−4.3 to 4.3]	0.139
Trail making test B, s	−9.5±23.1	−19.8±47.4	7.1 [−14 to 29]	0.514
Digit symbol coding, number coded in 2 min	−0.18±8.7	2.2±6.2	−2.1 [−6.9 to 2.6]	0.372
Incidental learning pairing	1.0±3.7	1.3±2.8	−0.16 [−2.2 to 1.8]	0.876
Incidental learning free recall	0.27±1.3	0.36±0.90	−0.09 [−0.78 to 0.61]	0.802
Stroop
Naming, s	−0.89±5.5	−4.2±11.3	1.05 [−4.1 to 6.2]	0.683
Reading, s	−0.16±4.1	−3.2±11.4	1.04 [−3.1 to 5.2]	0.614
Inhibition, s	−6.0±18.5	−5.2±16.4	−4.4 [−14.0 to 5.2]	0.354
Inhibition switching, s	1.1±11.3	−1.4±15.2	0.99 [−8.3 to 10.2]	0.830
Inhibition vs naming, scale	0.3±2.3	0.16±2.9	0.22 [−1.3 to 1.8]	0.773
Inhibition/switching vs naming+ reading, scale	−2.8±2.3	−1.1±2.6	0.42 [−1.2 to 2.1]	0.802
Inhibition/switching vs inhibition, scale	−0.78±3.1 [23]	−0.74±3.6 [21]	−0.42 [−2.2 to 1.4]	0.891
Verbal fluency, D‐KEFS
Total correct	1.7±6.7	1.7±6.8	0.30 [−4.1 to 4.6]	0.890
Total set loss errors	−0.57±3.0	−0.43±2.3	−0.023 [−1.2 to 1.2]	0.970
Total rep errors	0.67±2.6	−0.10±1.8	1.06 [−0.16 to 2.3]	0.087
Scaled score	0.524±2.1 [23]	0.455±2.1 [21]	0.154 [−1.2 to 1.5]	0.817
Erickson spatial matching task
1‐item reaction time	−28.1±194	30.4±141	−34.8 [−136 to 67]	0.491
1‐item accuracy	0.03±0.23	−0.011±0.14	0.02 [−0.11 to 0.15]	0.754
2‐item reaction time	−10.2±228.9	9.6±127.4	−22.6 [−143 to 97]	0.704
2‐item accuracy	0.10±0.26	0.03±0.16	0.038 [−0.09 to 0.17]	0.555
3‐item reaction time	9.6±185.8	−6.5±146	17.5 [−85 to 120]	0.729
3‐item accuracy	0.10±0.21 [17]	0.04±0.19 [15]	0.062 [−0.05 to 0.18]	0.273

$\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$, mL∙kg⁻¹∙min⁻¹ indicates oxygen uptake at the ventilatory anaerobic threshold; 1RM, 1 repetition maximum; ADL/IADL, activities of daily living/instrumental activities of daily living; DKEFS, Delis‐Kaplan Executive Function System (letters FAS at baseline and BHR at 24 weeks); HIIT, high‐intensity interval training; MICT, moderate‐intensity interval training; MoCA, Montreal Cognitive Assessment; and SF‐12, 12‐item Short Form Survey.

^*Adjusted for baseline values.

^† Based on Log transformed data.

Secondary Outcomes

There was a statistically significant greater increase in $\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$ for HIIT versus MICT with a mean difference of 2.07 mL·kg⁻¹·min⁻¹ [95% CI, 0.59–3.6] with a large n² _P of 0.197 (Table 2). There were no other significant between‐group differences. See Table S2 for baseline values.

Adherence and Per‐Protocol Analysis

Of all participants (including withdrawals), attendance to supervised sessions was 86% (n=62.7±9.7 sessions (total: 2922 sessions]) with no significant difference between HIIT (88±17%; n=63.2±12 sessions) and MICT (85±9%; n=61.1±6.7 sessions), P=0.478 (Table 1). Both groups completed comparable home‐based aerobic training sessions (P=0.370). The results of the per‐protocol analysis were similar to the main results (see Data S1; Table S3).

Treatment Fidelity (Acute Intensity Measures at 8 and 24 Weeks)

Treadmill speed and grade during 30‐second HIIT intervals were significantly higher than those during MICT at 8 weeks and 24 weeks (P<0.001) (Table S4). Likewise, 2‐minute HIIT speed and grade were significantly higher than MICT at 24 weeks (P<0.001). Exercise duration (excluding warm‐up and cool‐down) was longer during MICT sessions than HIIT sessions at both time points (P<0.001). Speed and duration of MICT significantly increased from 8 to 24 weeks, while speed increased from 8 to 24 weeks for 30‐second HIIT (P<0.037, all).

Total Session Intensity

Mean session V̇O₂ and $\%\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ was lower during MICT compared with during the 2 HIIT protocols at 24 weeks but was similar to the 30‐second protocol at 8 weeks.

Peak Bout Intensity

Mean V̇O₂, and HR during 30‐second intervals (excluding recovery intervals) were significantly higher than during MICT at 8 and 24 weeks. Mean V̇O₂ and HR were higher during 2‐minute intervals than MICT at 24 weeks. Relative to values on the baseline and 12‐week CPET, 30‐second HIIT intervals measured 101±22% and 106±15% of $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ at 8 and 24 weeks, respectively, and during the 2‐minute intervals reached 112±14% at 24 weeks. In contrast, MICT sessions measured 87±18% and 84±14% of baseline and 12‐week $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ at 8 and 24 weeks, respectively. In like manner, percentage of HRR was significantly higher for HIIT exercise routines than MICT (P<0.001). Comparison between the 2 HIIT exercise routines at 24 weeks revealed that mean V̇O₂ was higher during the 2‐minute workout (25.4±6.6 versus 23.3±5.5 mL·kg⁻¹·min⁻¹, P=0.030) and higher when expressed as $\%\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ (111.9±14.2 versus 105.9±14.6, P=0.04), but no significant differences in mean HR (P=0.281) or %HRR (P=0.362) were observed. Three participants exercised at the same speed during the 2‐min and 30‐sec intervals. Five HIIT and 1 MICT participant had progressed to jogging.

Adverse Events

There were no study‐related serious adverse events. However, there were 33 AEs in 23 participants (HIIT: 16 AEs in 10 participants, 10/24=42%; MICT: 17 AEs in 13 participants, 13/23=56.5%; Table S5). There were 6 participants with 7 severe AEs (Grade 3) over the period of participation that were not related to the intervention; 2/23 MICT=9% and 4/24=18% HIIT participants. These included a small bowel bleed that required blood transfusions (MICT; discontinued study), a fall sustained on holiday that required staples in the scalp (MICT), orthostatic hypotension because of overmedication (twice in same HIIT participant), and a fall on ice with concussion (HIIT), gall bladder surgery (HIIT; discontinued study), kidney stones (HIIT).

DISCUSSION

We investigated the potential impact of adding a novel HIIT protocol into a comprehensive exercise‐based rehabilitation program on CRF and walking capacity indices. Replacing 3 MICT sessions with 3 HIIT sessions resulted in more than a 2‐fold greater improvement in CRF over the course of a 6‐month program than 5 sessions/week of MICT. The magnitude of the difference in $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ (3.2 mL·kg⁻¹·min⁻¹) exceeded the clinically important difference of 2.5 mL·kg⁻¹·min^{−1 7} , ¹⁰ , ¹¹ , ¹³ with a large effect size. However, HIIT did not produce more beneficial results than MICT regarding 6MWD, and our null hypothesis was not rejected. This was explained mostly by the marked increase in 6MWD for both HIIT and MICT groups (83.4 and 70.9 m, respectively), which was almost 3 times the minimal clinically important difference of 25 m and exceeded what is considered a large improvement (50 m). ⁷² , ⁷³ These large improvements are remarkable given that 89% of the participants were more than 6 months poststroke and past the optimal time for a change in 6MWD. ¹⁵ Among secondary outcomes, the only between‐group difference was the increase in $\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$, which was greater in HIIT than in MICT. Although this was a secondary outcome, it is of notable clinical relevance as $\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$ has been identified as an important adjunct to $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ for establishing cardiovascular mortality risk. ⁷⁴

In addition, both HIIT and MICT groups had similar and excellent adherence to supervised and home‐based sessions, with less than 5% attrition per group over 6 months of training. Long‐term exercise adherence after the supervised period is also important when determining the optimal exercise prescription to improve walking capacity and CRF. This is being measured as a follow‐up to the current study and will be reported in a subsequent publication. AEs were also similar between groups and consistent with similar studies despite the current study being longer in duration. ²⁴ , ²⁶

Our novel training method used shorter and longer HIIT intervals to target neuromuscular and cardiovascular adaptations, resulting in a greater change in $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ in HIIT versus MICT. This work adds to the limited HIIT research in people poststroke. Hsu et al compared longer duration HIIT (3‐minute high‐intensity intervals with 3‐minute active recovery; n=10) versus MICT (n=13) ²⁴ and reported a greater increase in $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ and systemic tissue oxygen extraction in HIIT versus MICT and a significant improvement in peak cardiac output in HIIT alone. Boyne et al targeted walking capacity during 12‐weeks of mostly treadmill training ²⁶ and reported that short‐duration high‐intensity intervals (30 seconds with 30–60 seconds passive recovery) might partially explain a change in 6MWD for HIIT (71 m) versus MICT (27 m) but found no between‐group difference in $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ (~19% in HIIT versus 12% in MICT). Shorter duration high‐intensity intervals allow for faster treadmill speeds and large motor unit recruitment, while longer duration high‐intensity intervals result in higher mean and peak lactate concentrations. ⁷⁵ Growing evidence shows that more than 30 seconds of high‐intensity exercise is needed to increase cardiac stroke volume and reach VO_2max. ²⁸ , ²⁹ Indeed, our result of a greater change in $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ indicates longer intervals may be needed to drive $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ change. This is supported by the significantly higher mean V̇O₂ and $\%\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ during the 2‐minute than the 30‐second peak bout intervals measured acutely in the current study. Additionally, a longer high‐intensity interval would provide a greater aerobic stimulus for participants unable to walk faster during a shorter versus longer interval, as occurred with 3 HIIT participants in the current study. Future studies should consider contrasting the effect of different HIIT work durations, work‐to‐rest ratios, and exercise modalities in subgroups of patients on health‐related outcomes. This would allow tailored HIIT exercise prescriptions based on participant characteristics and desired outcomes.

The current study extends the results of Hsu et al, ²⁴ revealing further evidence of cardiovascular adaptations as the underlying mechanisms of the greater change in $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ in HIIT versus MICT rather than neuromotor or other factors. In the current study, the respiratory exchange ratio achieved at peak effort on the CPET did not change from baseline to 24 weeks in either group with no between‐group difference. This suggests that relative effort on the 24‐week CPET was not a factor in the greater change in $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ in HIIT. In addition, factors that have been associated with $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ in stroke studies that can improve with exercise training ³⁰ , ⁷⁶ , ⁷⁷ , ⁷⁸ were not augmented in HIIT compared with MICT, specifically 6MWD, 10‐m gait‐velocity, gait‐economy, leg‐extension strength, cognition, and balance. Finally, the greater improvement in $\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$ in HIIT compared with MICT corroborates a cardiovascular effect, as $\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$ does not necessitate reaching a true physiological maximum on the CPET that may not occur owing to noncardiovascular end points poststroke. ²⁷

Unlike Boyne et al, ²⁶ we did not observe between‐group differences in 6MWD. The 12‐week study duration of Boyne et al may not have been long enough for the MICT group to optimize walking capacity. Also, given that not all participants achieve a true physiological maximum on the CPET, ²⁷ we trained the MICT group to target intensity levels based on their $\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$ and not by a percentage of their peak CPET V̇O₂. Training at $\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$ prevents undertraining and promotes peripheral lactate clearance, allowing greater walking speed for a prolonged period of time. ⁷⁹ This may explain why the magnitude of the increase in 6MWD achieved by the MICT group in our study was the same as the change reported by Boyne et al but in the HIIT group. While further investigation is required, especially for overground training protocols, prescribing MICT at the $\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$ may optimize change in 6MWD poststroke rather than necessitating a HIIT intervention. Indeed, harness‐supported, inclined treadmill training may have allowed participants in both groups to reach target intensities not achievable with overground exercise. Furthermore, despite the greater increase in $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ and $\dot{\mathrm{V}}{\mathrm{O}}_{2\mathrm{VT}1}$ in HIIT versus MICT in the current study, this did not translate to a between‐group difference in 6MWD in contrast to what was reported by Boyne et al (ie, no difference in $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ but a difference in 6MWD). This may reflect the low to moderate correlation between $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ and walking speed and distance. ³⁰

Only one small study has contrasted the effect of HIIT versus MICT on cognition poststroke; demonstrating similar results to the current study. Hsu et al ²⁴ demonstrated no between‐group or within‐group change in cognition despite a greater increase in cerebral tissue oxygen utilization in HIIT versus MICT and a decrease in brain‐derived neurotrophic factor in MICT and increase in HIIT. Although there may be increased peripheral concentrations of brain‐derived neurotrophic factor in higher‐intensity exercise, it does not necessarily reflect circulating cerebral levels or increased central diffusion and may require a concurrent cognitive stimulus, but further research is required. ⁸⁰ , ⁸¹

Limitations

Some limitations should be considered when interpreting the results of this clinical trial. This study was a single‐center design, which limits generalizability; however, the baseline $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$, 6MWD, age, and comorbidities are representative of patients with chronic stroke. ¹⁵ The proportion of women was reflective of clinical program referrals, ⁸² and the sample was racially and ethnically diverse. Assessors of 6MWD were not blinded to group allocation, but instructions were standardized.

CONCLUSIONS

Among people with poststroke gait dysfunction, HIIT resulted in a significant and clinically important greater change in $\dot{\mathrm{V}}{\mathrm{O}}_{2\text{peak}}$ compared with MICT in this randomized clinical study. Both groups had similar and marked increases in 6MWD. HIIT was safe, and adherence was high. These findings show proof of concept that HIIT yields greater improvement in cardiorespiratory fitness than conventional MICT in appropriately screened individuals.

Sources of Funding

This work was supported by a grant‐in‐aid from the Heart and Stroke Foundation of Canada (S.M. and P.O. are the grant holders), and Heart and Stroke Foundation Canadian Partnership for Stroke Recovery Catalyst Grant.

Disclosures

None.

Supporting information

Data S1

Tables S1–S5

References 21,83–109