Research

JAMA Cardiology | Original Investigation

Short-term and Long-term Feasibility, Safety, and Efficacy

of High-Intensity Interval Training in Cardiac Rehabilitation
The FITR Heart Study Randomized Clinical Trial
Jenna L. Taylor, PhD; David J. Holland, MBBS, PhD; Shelley E. Keating, PhD; Michael D. Leveritt, PhD;
Sjaan R. Gomersall, PhD; Alex V. Rowlands, PhD; Tom G. Bailey, PhD; Jeff S. Coombes, PhD

Supplemental content
IMPORTANCE High-intensity interval training (HIIT) is recognized as a potent stimulus for
improving cardiorespiratory fitness (volume of oxygen consumption [VO2] peak) in patients
with coronary artery disease (CAD). However, the feasibility, safety, and long-term effects of
HIIT in this population are unclear.

OBJECTIVE To compare HIIT with moderate-intensity continuous training (MICT) for

feasibility, safety, adherence, and efficacy of improving VO2 peak in patients with CAD.

DESIGN, SETTING, AND PARTICIPANTS In this single-center randomized clinical trial,

participants underwent 4 weeks of supervised training in a private hospital cardiac
rehabilitation program, with subsequent home-based training and follow-up over 12 months.
A total of 96 participants with angiographically proven CAD aged 18 to 80 years were
enrolled, and 93 participants were medically cleared for participation following a
cardiopulmonary exercise test. Data were collected from May 2016 to December 2018, and
data were analyzed from December 2018 to August 2019.

INTERVENTIONS A 4 × 4-minute HIIT program or a 40-minute MICT program (usual care).

Patients completed 3 sessions per week (2 supervised and 1 home-based session) for 4 weeks
and 3 home-based sessions per week thereafter for 48 weeks.

MAIN OUTCOMES AND MEASURES The primary outcome was change in VO2 peak during the
cardiopulmonary exercise test from baseline to 4 weeks. Further testing occurred at 3, 6, and
12 months. Secondary outcomes were feasibility, safety, adherence, cardiovascular risk
factors, and quality of life.

RESULTS Of 93 randomized participants, 78 (84%) were male, the mean (SD) age was 65 (8)
years, and 46 were randomized to HIIT and 47 to MICT. A total of 86 participants completed
testing at 4 weeks for the primary outcome, including 43 in the HIIT group and 43 in the MICT
group; 69 completed testing at 12 months for VO2 peak, including 32 in the HIIT group and 37
in the MICT group. After 4 weeks, HIIT improved VO2 peak by 10% compared with 4% in the
MICT group (mean [SD] oxygen uptake: HIIT, 2.9 [3.4] mL/kg/min; MICT, 1.2 [3.4] mL/kg/min;
P = .02). After 12 months, there were similar improvements from baseline between groups,
with a 10% improvement in the HIIT group and a 7% improvement in the MICT group (mean
[SD] oxygen uptake: HIIT, 2.9 [4.5] mL/kg/min; MICT, 1.8 [4.3] mL/kg/min; P = .30). Both
groups had high feasibility scores and low rates of withdrawal due to serious adverse events
(3 participants in the HIIT group and 1 participant in the MICT group). One event occurred
following exercise (hypotension) in the HIIT group. Over 12 months, both home-based HIIT
and MICT had low rates of adherence (HIIT, 18 of 34 [53%]; MICT, 15 of 37 [41%]; P = .35)
compared with the supervised stage (HIIT, 39 of 44 [91%]; MICT, 39 of 43 [91%]; P > .99).

CONCLUSIONS AND RELEVANCE In this randomized clinical trial, a 4-week HIIT program
improved VO2 peak compared with MICT in patients with CAD attending cardiac
rehabilitation. However, improvements in VO2 peak at 12 months were similar for both
groups. HIIT was feasible and safe, with similar adherence to MICT over 12-month follow-up.
Author Affiliations: Author
These findings support inclusion of HIIT in cardiac rehabilitation programs as an adjunct or
affiliations are listed at the end of this
alternative modality to moderate-intensity exercise. article.

TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry Identifier: Corresponding Author: Jenna L.
Taylor, PhD, Department of
ACTRN12615001292561
Cardiovascular Medicine, Mayo Clinic,
JAMA Cardiol. 2020;5(12):1382-1389. doi:10.1001/jamacardio.2020.3511 200 1st St SW, Rochester, MN 55902
Published online September 2, 2020. (taylor.jenna-lee@mayo.edu).

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 Short-term and Long-term Feasibility, Safety, and Efficacy of High-Intensity Interval Training in Cardiac Rehabilitation
C
ardiac rehabilitation (CR) is an essential component in
the secondary prevention of coronary artery disease
(CAD), with proven reductions in cardiovascular and all-
cause mortality.1 Exercise plays an important role as cardiores-
piratory fitness (measured as volume of oxygen consumption
[VO2] peak) exerts the largest influence on cardiovascular dis-
ease prognosis in this population.2,3 High-intensity interval train-
ing (HIIT) has shown superior improvements in VO2 peak com-
pared with moderate-intensity continuous training (MICT) in
patients with CAD.4,5 However, current international CR guide-
lines dictate a need for further investigation into the feasibil-
ity, safety, and long-term adherence associated with HIIT.6
The primary aim of this investigator-initiated study was
to compare the efficacy of HIIT with MICT for improving VO2
peak during a 4-week supervised hospital-based CR pro-
gram. Secondary aims investigated the efficacy of HIIT com-
pared with MICT for improving VO2 peak following a super-
vised CR program over 12-month follow-up and whether
implementation of a HIIT program was safe and feasible, pro-
moted greater exercise adherence, modified cardiovascular risk
factors, and improved quality of life.
Methods
A detailed trial protocol for the Feasibility, Safety, Adher-
ence, and Efficacy of High Intensity Interval Training in
Rehabilitation for Coronary Heart Disease (FITR Heart Study)
is available in Supplement 1.7 This trial was approved by both
UnitingCare Health and the University of Queensland ethics
committees. All participants provided written informed
consent.
Patient Selection and Allocation
Patients were considered for inclusion in the study if they had
angiographically proven CAD, were aged 18 to 80 years, and
were eligible to participate in the hospital CR program. Pa-
tients were excluded if they had any absolute or relative con-
traindications to exercise testing.7,8 After providing consent,
participants underwent baseline testing before 1:1 randomiza-
tion to either HIIT or MICT (usual care) (Figure). All partici-
pants underwent a medically supervised cardiopulmonary ex-
ercise test (CPET). Patients were further excluded from the
study if abnormal results identified from the baseline CPET re-
sulted in further angiography or recommended exclusion by
the patients’ treating physician.
Outcome Measures
The primary outcome (VO2 peak) was measured by CPET at
baseline and 4 weeks. Further testing occurred at 3, 6, and 12
months. Safety was assessed continuously throughout the
study period. Adherence to the exercise protocol was as-
sessed as 70% attendance or higher at the recommended num-
ber of exercise sessions when training at the prescribed exer-
cise intensity during the exercise sessions (eMethods in
Supplement 2). Data were also obtained for anthropometric
measures, fasting blood markers, supine blood pressure, ha-
bitual dietary intake, physical activity (by accelerometry), and
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Original Investigation Research
Key Points
Question Is high-intensity interval training (HIIT) superior to
moderate-intensity continuous training (MICT) for improving
cardiorespiratory fitness during a 4-week hospital-based cardiac
rehabilitation program and long-term with home-based training
over 12 months?
Findings In this randomized clinical trial including 93 participants,
cardiorespiratory fitness significantly improved by 10% with HIIT
compared with 4% with MICT after the 4-week cardiac
rehabilitation program. Over 12 months, both HIIT and MICT were
safe and feasible and offered similar improvements in
cardiorespiratory fitness (by 10% and 7%, respectively).
Meaning This study supports using HIIT as an alternative or
adjunct form of exercise prescription in cardiac rehabilitation.
participant questionnaires related to feasibility, quality of life,
and exercise enjoyment.7
Exercise Protocols
The HIIT protocol involved 4 × 4-minute high-intensity inter-
vals corresponding to a rating of perceived exertion (RPE) of
15 to 18 on the Borg 6 to 20 scale,9 interspersed with 3-min-
ute active recovery intervals (RPE of 11 to 13). The MICT pro-
tocol involved usual care exercise of 40-minute moderate-
intensity exercise at an RPE of 11 to 13 (eMethods in
Supplement 2). Participants were instructed to complete 3 ses-
sions of their allocated training per week (2 supervised and 1
home-based session) during the 4-week CR program and then
to continue home-based training (at least 3 sessions per week
of their allocated training) for a further 11 months.
Statistical Analysis
The sample size calculation conducted for the primary out-
come, the comparison of groups for change in VO2 peak over
a 4-week supervised program, determined 80 participants (40
per group) would be sufficient to detect a 1–metabolic equiva-
lent difference (3.5 mL/kg/min) between groups with an SD of
4.75 mL/kg/min and a power of 0.9 at an α of .05.7 Intention-
to-treat analyses using linear mixed modeling were per-
formed to investigate the time and group interaction effects
for the supervised study period (baseline to 4 weeks) and 12-
month period (all time points). Baseline characteristics and ex-
ercise adherence data were compared using t tests for con-
tinuous variables and Fisher exact test for categorical data.
Prespecified per-protocol analyses were conducted includ-
ing only participants meeting the criteria for exercise
adherence.7 Sensitivity analyses were conducted to account
for medication changes. Statistical analyses were performed
using SPSS Statistics version 25 (IBM). Significance was set at
a P value less than .05, and all P values were 2-tailed.
Results
Participant Characteristics
A total of 96 participants were recruited between May 2016 and
November 2017. The Figure outlines allocation to the HIIT and
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 Research Original Investigation Short-term and Long-term Feasibility, Safety, and Efficacy of High-Intensity Interval Training in Cardiac Rehabilitation
Figure. CONSORT Flowchart of Study Enrollment, Allocation, and Follow-up
406 Assessed for eligibility
93 Randomized
46 Randomized to HIIT
44 Received the intervention as randomized
2 Did not receive intervention as randomized
2 Withdrew
44 Analyzed at 4 wk
43 With VO2 peak measurements
1 Did not complete exercise testing at 4 wk
37 Analyzed at 3 mo
37 With VO2 peak measurements
5 Failed to attend further follow-up testing
1 Withdrew
1 Did not complete any testing at 3 mo
38 Analyzed at 6 mo
35 With VO2 peak measurements
3 Did not complete exercise testing at 6 mo
34 Analyzed at 12 mo
32 With VO2 peak measurements
3 Failed to attend further follow-up testing
2 Did not complete exercise testing at 12 mo
1 Withdrew
MICT groups after exclusions. A total of 3 of 96 participants
(3%) were medically excluded following baseline CPET, with
1 of 96 participants (1%) requiring further coronary interven-
tion. Of 93 randomized participants, 78 (84%) were male, the
mean (SD) age was 65 (8) years, and 46 were randomized to
HIIT and 47 to MICT. Dropout rates between HIIT (12 of 46
[26%]) and MICT (8 of 47 [17%]) were not different over 12-
month follow-up (P = .32). A total of 86 participants com-
pleted testing at 4 weeks for the primary outcome, including
43 in the HIIT group and 43 in the MICT group; 69 completed
testing at 12 months for VO2 peak, including 32 in the HIIT group
and 37 in the MICT group. Baseline characteristics are out-
lined in Table 1. For medication adjustments, see eTable 1 in
Supplement 2.
Cardiorespiratory Fitness
Following the 4-week supervised program, VO 2 peak in-
creased by 10% with HIIT and 4% with MICT (mean [SD] oxy-
gen uptake: HIIT, 2.9 [3.4] mL/kg/min; MICT, 1.2 [3.4] mL/kg/
min; mean difference [MD], 1.7 mL/kg/min; P = .02) (Table 2).
This was similar for VO2 peak normalized for lean body mass
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313 Excluded
178 Declined to participate
117 Did not have angiographically proven CAD
12 Met medical exclusion criteria
3 Had cardiologist decline participation
3 Had electrically positive findings on
baseline exercise test
47 Randomized to MICT
44 Received the intervention as randomized
3 Did not receive intervention as randomized
2 Failed to attend intervention and further
follow-up testing
1 Withdrew
43 Analyzed at 4 wk
43 With VO2 peak measurements
1 Did not complete any testing at 4 wk
41 Analyzed at 3 mo
40 With VO2 peak measurements
1 Failed to attend further follow-up testing
1 Withdrew
1 Did not complete any testing at 3 mo
1 Did not complete exercise testing at 3 mo
39 Analyzed at 6 mo Participants underwent 4 weeks of
39 With VO2 peak measurements supervised training in a private
2 Did not complete any testing at 6 mo hospital cardiac rehabilitation
1 Failed to attend further follow-up testing
program, with subsequent
home-based training and follow-up
39 Analyzed at 12 mo over 12 months. CAD indicates
37 With VO2 peak measurements coronary artery disease;
2 Failed to attend further follow-up testing HIIT, high-intensity interval training;
2 Did not complete exercise testing at 12 mo MICT, moderate-intensity continuous
training; VO2, volume of oxygen
consumption.
(mean [SD] oxygen uptake: HIIT, 4.1 [4.9] mL/kg/min [10% im-
provement]; MICT, 1.0 [5.0] mL/kg/min [2% improvement]; MD,
3.1 mL/kg/min; P = .004) (Table 2). After 12-month follow-up,
participants in the HIIT and MICT groups showed similar im-
provement in VO2 peak from baseline, with a 10% improve-
ment in the HIIT group and a 7% improvement in the MICT
group (mean [SD] oxygen uptake: HIIT, 2.9 [4.5] mL/kg/min;
MICT, 1.8 [4.3] mL/kg/min; MD, 1.1 mL/kg/min; P = .30).
Safety
There were 9 serious adverse events reported during the study
period, including 6 in the HIIT group and 3 in the MICT group
(eTable 2 in Supplement 2). None of these were deemed by the
treating physician to be a result of exercise training.
Exercise Adherence
Average training RPE was higher for HIIT compared with MICT
(mean [SD] RPE: HIIT, 16.3 [1.3]; MICT, 12.4 [0.6]; P < .001), as
was average training heart rate as a percentage of peak heart
rate (mean (SD) percentage: HIIT, 87% [6]; MICT, 71% [8];
P < .001) (eTable 3 in Supplement 2). In stage 2 (home-based
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 Short-term and Long-term Feasibility, Safety, and Efficacy of High-Intensity Interval Training in Cardiac Rehabilitation Original Investigation Research

Table 1. Participant Characteristics at Baseline

No. (%)
Characteristic HIIT (n = 46) MICT (n = 47) P value
Male 39 (85) 39 (83) >.99
Age, mean (SD), y 65 (7) 65 (8) .98
Body mass index, mean (SD)a 28.2 (4.2) 28.5 (4.2) .67
Blood pressure, mean (SD), mm Hg
Systolic 128 (15) 130 (14) .62
Diastolic 75 (10) 74 (9) .72
Resting heart rate, mean (SD), beats/min 57 (10) 57 (8) .92
Reason for hospital admission
Acute coronary syndrome 13 (28) 16 (34) .66
ST-elevation myocardial infarction 1 (2) 9 (19) .02
Non–ST-elevation myocardial infarction 8 (17) 6 (13) .57
Unstable angina pectoris 4 (9) 1 (2) .20
Diagnostic angiography only 33 (72) 31 (66) .66
Coronary intervention
Coronary artery bypass grafting 15 (33) 11 (23) .36
Percutaneous coronary intervention 23 (50) 23 (49) >.99
Medical therapy only 8 (17) 13 (28) .32
Comorbidities
Diabetes 2 (4) 7 (15) .16
Current smoking 1 (2) 2 (4) >.99
Left ventricular dysfunctionb 3 (7) 5 (11) .72
Chronic atrial fibrillation 1 (2) 1 (2) >.99
Medications Abbreviations: HIIT, high-intensity
β-Blocker 18 (39) 20 (43) .83 interval training;
Angiotensin-converting enzyme inhibitor 9 (20) 17 (36) .11 MICT, moderate-intensity continuous
training.
Angiotensin II receptor blocker 16 (35) 16 (34) >.99 a
Calculated as weight in kilograms
Calcium channel blocker 3 (7) 6 (13) .49 divided by height in meters
Diuretic 7 (15) 7 (15) >.99 squared.
b
Antiarrhythmic 2 (4) 2 (4) >.99 Left ventricular dysfunction was
defined either quantitatively
Anticoagulant 4 (9) 1 (2) .20
(ejection fraction less than 50%) or
Statin 45 (98) 44 (94) .62 qualitatively from the patient’s most
Aspirin 44 (96) 43 (92) .68 recent echocardiography or left
heart ventriculography during
Other antiplatelet 25 (54) 27 (57) .84
angiography procedure.

training), average training RPE was maintained at similar lev- Feasibility

els despite reduced supervision. Exercise adherence was high
during the initial supervised stage (HIIT, 39 of 44 [91%]; MICT,
39 of 43 [91%]; P > .99) and reduced over the 12-month study
period (HIIT, 18 of 34 [53%]; MICT, 15 of 37 [41%]; P = .35), with
no differences between groups (eTable 4 in Supplement 2). Af-
ter 6 months of home-based training, we observed a reduc-
tion in the number of participants training at the prescribed
intensity, with 15 of 39 participants in the MICT group (38%)
exercising at a higher intensity on their own accord and 9 of
37 participants in the HIIT group (24%) exercising at a lower
intensity (eTable 4 in Supplement 2). Based on adherence to
attendance and intensity, per-protocol analysis showed that
HIIT was superior to MICT for improving VO2 peak at 12 months
(HIIT, 5.2 [4.1] mL/kg/min [18% improvement]; MICT, 2.2
[4.1] mL/kg/min [8% improvement]; MD, 3.0 mL/kg/min;
P = .02) (eTable 5 in Supplement 2).
Both HIIT and MICT reported high feasibility of the exercise
protocols throughout the study period (eTable 6 in Supple-
ment 2). The frequency and reasons stated for being unable
to complete the exercise protocol were similar between groups,
as well as unpleasant symptoms and injuries reported in re-
lation to the exercise protocols.
Additional Outcomes
Following supervised training, there was a decrease in blood
pressure after MICT compared with HIIT for both systolic pres-
sure (mean [SD] blood pressure: HIIT, 2 [11] mm Hg; MICT, −3
[12] mm Hg; MD, 5 mm Hg; P = .03) and diastolic pressure
(mean [SD] blood pressure: HIIT, 1 [6] mm Hg; MICT, −2 [6] mm
Hg; MD, 3 mm Hg; P = .04) (Table 2). In contrast, similar sig-
nificant reductions in blood pressure were observed with both
HIIT and MICT in patients with hypertension at baseline

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 1386
Table 2. Efficacy Results for Cardiorespiratory Fitness, Exercise Testing Variables, Cardiorespiratory Risk Factors, and Quality of Life

Supervised training (stage 1) Home-based training (stages 2 and 3), mean within-group difference (95% CI) P value
Change in 4 wk, mean
within-group difference
Baseline, mean (SD) (95% CI) P value, Change in 3 mo Change in 6 mo Change in 12 mo
time × Time ×
Outcome measure No. HIIT MICT HIIT MICT group HIIT MICT HIIT MICT HIIT MICT Time group
Cardiorespiratory fitness
and exercise testing
Peak oxygen uptake, 93 27.7 (6.1) 27.4 (7.4) 2.9 (1.9 to 1.2 (0.2 to .02 2.6 (0.8 to 2.2 (0.5 to 3.1 (1.3 to 1.7 (0 to 2.9 (1.0 to 1.8 (0 to <.001 .30
Research Original Investigation

mL/kg/min, total body 3.9)a 2.2)a 4.4)a 4.0)a 4.9)a 3.5) 4.8)a 3.6)a
weight
Peak oxygen uptake, 93 41.3 (7.1) 42.0 (9.4) 4.1 (2.7 to 1.0 (−0.4 to .004 3.1 (0.5 to 2.0 (−0.6 to 3.7 (1.0 to 1.2 (−1.3 to 4.1 (1.4 to 1.8 (−0.9 to <.001 .14
mL/kg/min, lean body 5.5)a 2.5) 5.7)a 4.5) 6.3)a 3.8) 6.9)a 4.4)
mass

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Peak oxygen uptake, 93 2.33 (0.61) 2.39 (0.73) 0.23 (0.15 to 0.09 (0.01 to .02 0.18 (0.03 to 0.17 (0.02 to 0.21 (0.06 to 0.10 (−0.05 0.20 (0.04 to 0.11 (0.04 to <.001 .26
L/min 0.32)a 0.18)a 0.33)a 0.32)a 0.37)a to 0.25) 0.36)a 0.26)
Peak respiratory exchange 93 1.14 (0.09) 1.14 (0.09) −0.01 −0.01 .94 0.01 (−0.03 −0.01 −0.01 0.01 (−0.03 0 (−0.05 to 0.01 (−0.03 .41 .37
ratio (−0.04 to (−0.04 to to 0.05) (−0.05 to (−0.05 to to 0.05) 0.04) to 0.05)
0.02) 0.02) 0.03) 0.03)
Peak heart rate, 93 151 (17) 150 (20) 1 (−2 to 5) −2 (−5 to 2) .26 4 (−2 to 10) 3 (−3 to 9) 3 (−3 to 9) 3 (−3 to 9) 4 (−2 to 10) 7 (1 to 13)a <.001 .29
beats/min
Peak oxygen pulse, 93 15.5 (3.8) 15.9 (4.0) 1.5 (0.9 to 0.8 (0.2 to .14 0.8 (−0.3 to 0.7 (−0.4 to 1.0 (−0.1 to 0.2 (−0.9 to 0.9 (−0.3 to 0 (−1.1 to <.001 .34

JAMA Cardiology December 2020 Volume 5, Number 12 (Reprinted)

mL/beat 2.2)a 1.5)a 1.9) 1.8) 2.2) 1.3) 2.1) 1.4)
Maximal oxygen uptake 93 2.5 (0.7) 2.4 (0.6) 0.2 (0.1 to 0.2 (0.1 to .79 0.2 (0 to 0.2 (0 to 0.2 (0 to 0.1 (−0.1 to 0.1 (−0.1 to 0.1 (−0.1 to <.001 .57
efficiency slope 0.4)a 0.3)a 0.4)a 0.4) 0.4)a 0.3) 0.4) 0.3)
Abdominal obesity
Body mass, kg 93 84 (15) 87 (16) −0.4 (−0.8 to −0.5 (−0.9 to .79 −1.2 (−2.3 to −1.2 (−2.3 to −1.2 (−2.3 to −2.0 (−3.1 to −1.1 (−2.2 to −1.6 (−2.7 to <.001 .54
0.1) 0)a −0.1)a −0.2)a −0.1)a −0.9)a 0.1) −0.5)a
b
Body mass index 93 28.2 (4.2) 28.6 (4.2) −0.1 (−0.3 to −0.2 (−0.5 to .30 −0.4 (−0.8 to −0.5 (−0.9 to −0.4 (−0.8 to −0.8 (−1.2 to −0.4 (−0.8 to −0.7 (−1.1 to <.001 .35
0.2) 0) 0) −0.1)a 0) −0.4)a 0.1) −0.3)a
Waist circumference, cm 93 98.9 (12.3) 99.7 (11.9) −1.8 (−2.7 to −1.5 (−2.4 to .66 −2.4 (−4.0 to −2.2 (−3.7 to −2.7 (−4.3 to −3.5 (−4.1 to −2.6 (−4.2 to −3.5 (−5.1 to <.001 .34
−0.8)a −0.5)a −0.8)a −0.7)a −1.1)a −2.0)a −1.0)a −2.0)a
Waist-to-hip ratio 93 0.94 (0.09) 0.94 (0.08) −0.01 −0.01 .92 −0.02 −0.01 −0.02 −0.03 −0.02 −0.02 <.001 .44
(−0.02 to 0)a (−0.02 to 0)a (−0.03 to 0)a (−0.03 to 0)a (−0.03 to 0)a (−0.04 to 0)a (−0.03 to 0)a (−0.04 to 0)a
Waist-to-height ratio 93 0.57 (0.07) 0.57 (0.06) −0.01 −0.01 .82 −0.01 −0.01 −0.02 −0.02 −0.02 −0.02 <.001 .40
(−0.02 to 0)a (−0.01 to 0)a (−0.02 to (−0.02 to 0)a (−0.03 to (−0.03 to (−0.02 to (−0.03 to

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−0.01)a −0.01)a −0.01)a −0.01)a −0.01)a
Visceral adipose tissue 93 190 (75) 198 (74) −9 (−14 to −9 (−14 to .99 −13 (−24 to −17 (−27 to −14 (−25 to −18 (−29 to −7 (−18 to −16 (−26 to <.001 .52
measured by DEXA, cm2 −4)a −4)a −3)a −6)a −3)a −8)a 4) −5)a
Lipid profile
Total cholesterol, mg/dL 93 147 (31) 147 (31) −4 (−12 to 0 (−8 to 8) .36 0 (−12 to 8) 0 (−8 to 12) 4 (−15 to 8) 0 (−8 to 12) 0 (−12 to 12 (4 to 23)a .01 .28
4) 12)
LDL cholesterol, mg/dL 93 77 (27) 73 (23) −4 (−12 to 0 (−8 to 8) .28 −4 (−12 to 0 (−8 to 8) −4 (−12 to 0 (−8 to 12) −4 (−12 to 4 (−4 to 15) .70 .30
4) 8) 4) 4)
HDL cholesterol, mg/dL 93 50 (12) 50 (15) 0 (0 to 4) 0 (0 to 4) .88 4 (0 to 8)a 4 (0 to 4) 4 (0 to 4) 4 (0 to 4) 4 (0 to 4)a 4 (4 to 8)a <.001 .47
Triglycerides, mg/dL 93 124 (133) 106 (53) −18 (−35 to −9 (−27 to .60 −18 (−35 to −9 (−27 to −9 (−35 to 0 (−18 to −9 (−35 to 9 (−9 to 27) .06 .57
9) 9) 9) −9) 9) 18) 18)

(continued)

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Short-term and Long-term Feasibility, Safety, and Efficacy of High-Intensity Interval Training in Cardiac Rehabilitation
 Table 2. Efficacy Results for Cardiorespiratory Fitness, Exercise Testing Variables, Cardiorespiratory Risk Factors, and Quality of Life (continued)

Supervised training (stage 1) Home-based training (stages 2 and 3), mean within-group difference (95% CI) P value
Change in 4 wk, mean
within-group difference
Baseline, mean (SD) (95% CI) P value, Change in 3 mo Change in 6 mo Change in 12 mo

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time × Time ×
Outcome measure No. HIIT MICT HIIT MICT group HIIT MICT HIIT MICT HIIT MICT Time group
Glucose tolerance
Fasting glucose, mg/dL 93 106 (29) 110 (20) −4 (−11 to −4 (−7 to 7) .35 −2 (−11 to 2 (−5 to 9) −2 (−9 to 5) 4 (−4 to 11) −2 (−11 to 4 (−4 to 13) .66 .47
4) 5) 5)
Insulin resistance 93 2.7 (2.1) 2.5 (1.8) −0.2 (−0.7 to −0.2 (−0.7 to .96 −0.1 (−0.9 to −0.1 (−0.7 to −0.3 (−1.0 to −0.1 (−0.8 to 0.1 (−0.6 to 0 (−0.7 to .61 .90
measured by HOMA 0.3) 0.3) 0.6) 0.6) 0.4) 0.7) 0.9) 0.7)
Blood pressure
and heart rate
Peripheral systolic blood 93 128 (15) 130 (14) 2 (−1 to 5) −3 (−7 to 0) .03 0 (−5 to 6) −3 (−8 to 2) 1 (−5 to 6) −3 (−9 to 2) 2 (−4 to 7) 1 (−4 to 7) .60 .14

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pressure, mm Hg
Peripheral diastolic blood 93 75 (10) 74 (9) 1 (−1 to 3) −2 (−3 to 0) .04 0 (−3 to 3) −1 (−4 to 2) −1 (−4 to 2) −2 (−4 to 1) 0 (−3 to 3) 1 (−2 to 4) .10 .08
pressure, mm Hg
Resting heart rate, 93 57 (10) 57 (8) −3 (−4 to −1 (−3 to 1) .19 −3 (−6 to 0)a −2 (−5 to 1) −4 (−7 to −1 (−4 to 2) −3 (−6 to 0)a −2 (−5 to 1) .001 .18
beats/min −1)a −1)a
Quality of life and exercise
enjoyment
McNew Global score 93 5.9 (0.8) 6.0 (0.6) 0.5 (0.4 to 0.4 (0.2 to .17 0.5 (0.3 to 0.4 (0.2 to 0.5 (0.3 to 0.4 (0.2 to 0.5 (0.3 to 0.4 (0.2 to <.001 .46
0.7)a 0.5)a 0.7)a 0.6)a 0.7)a 0.6)a 0.7)a 0.6)a
McNew Physical score 92 5.8 (1.0) 5.9 (0.8) 0.7 (0.5 to 0.5 (0.2 to .17 0.7 (0.4 to 0.5 (0.3 to 0.7 (0.5 to 0.5 (0.3 to 0.7 (0.4 to 0.6 (0.4 to <.001 .31
0.9)a 0.7)a 1.0)a 0.8)a 1.0)a 0.8)a 1.0)a 0.9)a
McNew Emotional score 93 6.0 (0.6) 6.0 (0.6) 0.4 (0.2 to 0.2 (0.1 to .17 0.3 (0.1 to 0.2 (0 to 0.2 (0 to 0.2 (0 to 0.3 (0 to 0.1 (−0.1 to <.001 .55
0.5)a 0.4)a 0.5)a 0.4) 0.5)a 0.4) 0.5)a 0.3)
McNew Social score 92 5.7 (1.0) 6.0 (0.9) 0.9 (0.6 to 0.6 (0.3 to .12 0.9 (0.6 to 0.6 (0.4 to 0.9 (0.6 to 0.6 (0.3 to 0.9 (0.6 to 0.7 (0.4 to <.001 .14
1.1)a 0.8)a 1.1)a 0.9)a 1.2)a 0.9)a 1.2)a 0.9)a
Exercise enjoyment, % 92 74 (17) 78 (16) 3 (−2 to 8) 3 (−2 to 8) .96 6 (−1 to 13) −2 (−9 to 4) 1 (−6 to 8) −3 (−10 to −2 (−9 to 6) −5 (−11 to .02 .15
3) 2)
Abbreviations: DEXA, dual-energy x-ray absorptiometry; HDL, high-density lipoprotein; HIIT, high-intensity millimoles per liter, multiply by 0.0113; fasting glucose to millimoles per liter, multiply by 0.0555.
interval training; HOMA, homeostatic model assessment of insulin resistance; LDL, low-density lipoprotein; a
Significant difference from baseline.
MICT, moderate-intensity continuous training. b
Short-term and Long-term Feasibility, Safety, and Efficacy of High-Intensity Interval Training in Cardiac Rehabilitation

Calculated as weight in kilograms divided by height in meters squared.

SI conversion factors: To convert total cholesterol to millimoles per liter, multiply by 0.0259; LDL cholesterol to

© 2020 American Medical Association. All rights reserved.

millimoles per liter, multiply by 0.0259; HDL cholesterol to millimoles per liter, multiply by 0.0259; triglycerides to

(Reprinted) JAMA Cardiology December 2020 Volume 5, Number 12

Original Investigation Research

1387
 Research Original Investigation Short-term and Long-term Feasibility, Safety, and Efficacy of High-Intensity Interval Training in Cardiac Rehabilitation
(eTable 7 in Supplement 2). There were no group differences
for any other cardiovascular risk factors (Table 2) or mea-
sures related to diet and physical activity (eTable 8 in Supple-
ment 2). All quality of life domains improved over the study
period, with no differences between groups (Table 2).
Discussion
This investigator-initiated study found that a 4-week super-
vised HIIT program improved cardiorespiratory fitness more
than MICT without adversely affecting patient safety. How-
ever, the superior effect of HIIT was not maintained long term,
with similar improvements to MICT at 12 months. Implemen-
tation of the HIIT protocol using RPE for exercise intensity was
feasible. This should have broad applicability for traditional
CR and home-based programs.
The greater efficacy of HIIT for improving VO2 peak com-
pared with MICT during supervised training (MD, 1.7 mL/kg/
min) is similar to previous meta-analyses reporting group dif-
ferences of 1.5 to 1.6 mL/kg/min.4,5 This is clinically meaningful,
as each 1–mL/kg/min improvement in VO2 peak during a CR
program has been associated with a 6% reduction in hospital
readmissions and 13% reduction in all-cause mortality.10 At 12
months, both groups showed similar improvement in VO2 peak;
however, the MD between HIIT and MICT of 1.1 mL/kg/min
could be considered clinically meaningful.
The greater reduction in systolic and diastolic blood pres-
sure after short-term MICT compared with HIIT is in contrast
to a recent meta-analysis reporting similar mean reductions in
systolic (6 mm Hg) and diastolic (4 mm Hg) pressures for HIIT
and MICT.11 In patients with hypertension at baseline,12 both
HIIT and MICT reduced systolic and diastolic blood pressure.
This is similar to the findings by Sosner et al,13 where HIIT only
reduced blood pressure in those with initially elevated levels.
There were no deaths or cardiovascular events directly
caused by the exercise interventions during the study period.
One serious adverse event in the HIIT group occurred in rela-
tion to exercise training (postexercise hypotension); how-
ever, the treating physician diagnosed the cause as diuretic-
induced dehydration. These findings are consistent with
previous trials,14-17 which consistently demonstrate a favor-
able safety profile of HIIT programs. In the current study, medi-
cal exclusion following baseline CPET (3%) and further coro-
nary intervention (1%) were very low. However, these safety
data should still be interpreted in the context of the small size
of the study and the requirement that all patients have CPET
prior to enrollment, which is not routinely done for all pa-
tients referred for CR. To maximize safety in clinical popula-
tions, we have developed clinician guidelines for appropriate
screening and monitoring for HIIT implementation.18
A number of single-center trials6,9,19 have demonstrated
a 2-fold increase in VO2 peak with HIIT compared with MICT.
In contrast, the multicenter Study on Aerobic Interval Exer-
cise Training in Coronary Artery Disease Patients (SAINT
EX-CAD) study17 found no differences between HIIT and MICT
over 6 weeks and 12 weeks. There are a number of differences
between the SAINTEX-CAD study and our trial. Principally,
1388 JAMA Cardiology December 2020 Volume 5, Number 12 (Reprinted)
© 2020 American Medical Association. All rights reserved.
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during supervised training, the SAINTEX-CAD trial did not re-
strain moderate continuous training participants to exercise
at lower exercise intensities, with the notion that if higher in-
tensities of continuous training can be sustained, workloads
and heart rate zones should be modified for the greatest
improvement.17 During unsupervised training, we also found
a large proportion of participants in the MICT group (38%) ex-
ercising at a higher intensity (RPE of 15 or greater), indicating
that prescribing exercise at moderate intensity is potentially
not challenging enough for some patients. As a result of
participants not training at the prescribed intensity after 6
months, the per-protocol analysis at 12 months showed a dif-
ferent result to the intention-to-treat analysis. Instead, HIIT
demonstrated a superior effect on VO2 peak compared with
MICT, with a mean group difference of 3.0 mL/kg/min. These
results suggest that a superior benefit of HIIT may only per-
sist for those who maintain 3 HIIT sessions per week follow-
ing supervised CR.
Limitations
Our study had limitations. Patients were recruited from a single
center, and there were low rates of female patients and pa-
tients with left ventricular dysfunction, type 2 diabetes, and
a history of tobacco smoking. As the primary intervention was
conducted in a CR setting, optimization of drug therapy was
at the discretion of the treating physician. While RPE-based
prescription of exercise intensity is well accepted in CR and
broadens protocol applicability, we acknowledge RPE ranges
can result in a wide range of training intensities.20 Further-
more, despite patients receiving education from CR clini-
cians on how to progress their exercise protocols, there is lim-
ited published evidence that patients targeting an RPE range
will inherently increase their workload over time. There were
a number of patients who failed to maintain adherence to the
prescribed exercise program (although rates were equal in both
groups), and some participants in the MICT group exercised
more frequently and at higher intensities than prescribed, in-
creasing the likelihood of type 2 error. Additionally, the pro-
vision of heart rate monitors only for participants in the HIIT
group during the initial 3 months could have enhanced exer-
cise adherence, motivation, and achievement of intended heart
rate targets during the initial stages of home-based exercise.
Conclusions
This study demonstrates that HIIT is superior to MICT for im-
proving cardiorespiratory fitness during a 4-week hospital-
based CR program in patients with CAD but offers similar im-
provement to MICT at 12 months. The HIIT protocol was safe,
feasible, and successfully implemented in a home-based en-
vironment with similar adherence to MICT over 12 months. Fur-
ther improvement in cardiorespiratory fitness after 12 months
in patients undertaking HIIT was limited to those with good
exercise adherence. These findings support the inclusion of
HIIT in CR programs as an alternative or an adjunct to stan-
dard moderate-intensity exercise, allowing for prescription
based on patient goals, preferences, and capabilities.
jamacardiology.com
 Short-term and Long-term Feasibility, Safety, and Efficacy of High-Intensity Interval Training in Cardiac Rehabilitation
ARTICLE INFORMATION
Accepted for Publication: June 3, 2020.
Published Online: September 2, 2020.
doi:10.1001/jamacardio.2020.3511
Author Affiliations: Centre for Research on
Exercise, Physical Activity, and Health, School of
Human Movement and Nutrition Sciences, The
University of Queensland, Brisbane, Australia
(Taylor, Holland, Keating, Leveritt, Gomersall,
Bailey, Coombes); Cardiac Rehabilitation
Department, The Wesley Hospital, Brisbane,
Australia (Taylor); Department of Cardiology,
Sunshine Coast University Hospital, Birtinya,
Australia (Holland); School of Health and
Rehabilitation Sciences, The University of
Queensland, Brisbane, Australia (Gomersall);
Diabetes Research Centre, University of Leicester,
Leicester General Hospital, Leicester, United
Kingdom (Rowlands); NIHR Leicester Biomedical
Research Centre, Leicester, United Kingdom
(Rowlands).
Author Contributions: Dr Taylor had full access to
all of the data in the study and takes responsibility
for the integrity of the data and the accuracy of the
data analysis.
Study concept and design: Taylor, Holland,
Gomersall, Coombes.
Acquisition, analysis, or interpretation of data:
Taylor, Keating, Leveritt, Gomersall, Rowlands,
Bailey, Coombes.
Drafting of the manuscript: Taylor, Keating,
Gomersall.
Critical revision of the manuscript for important
intellectual content: Holland, Keating, Leveritt,
Gomersall, Rowlands, Bailey, Coombes.
Statistical analysis: Taylor, Coombes.
Obtained funding: Taylor, Keating, Coombes.
Administrative, technical, or material support:
Keating, Coombes.
Study supervision: Holland, Keating, Leveritt,
Gomersall, Bailey, Coombes.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported by
grant 2015-17 from Wesley Medical Research.
Dr Taylor was supported by postgraduate research
scholarships from the National Health and Medical
Research Council and the University of Queensland.
Dr Keating was supported by grant 1122190 from
the National Health and Medical Research Council
of Australia via an Early Career Research Fellowship.
Role of the Funder/Sponsor: The funders had
no role in the design and conduct of the study;
collection, management, analysis, and
interpretation of the data; preparation, review, or
approval of the manuscript; and decision to submit
the manuscript for publication.
Disclaimer: Dr Rowlands is with the National
Institute for Health Research Leicester Biomedical
Research Centre and the National Institute for
Health Research Collaboration for Leadership in
Applied Health Research and Care–East Midlands.
The views expressed are those of the authors and
not necessarily those of the UK National Health
Service, the National Institute for Health Research,
or the Department of Health.
Data Sharing Statement: See Supplement 3.
jamacardiology.com
© 2020 American Medical Association. All rights reserved.
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Additional Contributions: We thank the Wesley
Hospital Cardiac Rehabilitation Department,
UnitingCare Health, Brisbane, Australia, for allowing
access to patients for recruitment and providing the
working environment and staff for the supervised
exercise training. We also acknowledge Ravin Lal,
PhD (University of Queensland, Brisbane,
Australia), who assisted with exercise testing and
other forms of data collection through paid
employment. He was not otherwise compensated
for his work.
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