Authors:

Chul Kim, MD, PhD

Hee Eun Choi, MD Cardiac Rehabilitation
Min Ho Lim, MD

Affiliations:
From the Department of Physical
Medicine and Rehabilitation, Sanggye
Paik Hospital, Inje University College of
Medicine, Seoul (CK, MHL); and
Department of Physical Medicine and
Rehabilitation, Haeundae Paik
Hospital, Inje University College of
Medicine, Busan, South Korea (HEC).
Correspondence:
All correspondence and requests for
reprints should be addressed to: Hee
Eun Choi, MD, Department of Physical
Medicine and Rehabilitation, Haeundae
Paik Hospital, Inje University College of
Medicine, 875 Haeun-daero,
Haeundae-gu, Busan, South Korea.
Disclosures:
Financial disclosure statements have
been obtained, and no conflicts of
interest have been reported by the
authors or by any individuals in control
of the content of this article.
0894-9115/15/9410-0879
American Journal of Physical
Medicine & Rehabilitation
Copyright * 2015 Wolters Kluwer
Health, Inc. All rights reserved.
DOI: 10.1097/PHM.0000000000000290
ORIGINAL RESEARCH ARTICLE
Effect of High Interval Training in
Acute Myocardial Infarction Patients
with Drug-Eluting Stent
ABSTRACT
Kim C, Choi HE, Lim MH: Effect of high interval training in acute myocardial
infarction patients with drug-eluting stent. Am J Phys Med Rehabil
2015;94:879Y886.
Objective: Peak oxygen uptake (VO2peak) is a strong predictor of survival in
cardiac patients. The aims of this study were to compare the effects of high interval
training (HIT) to moderate continuous training (MCT) on VO2peak and to identify
the safety of HIT in acute myocardial infarction patients with drug-eluting stent.
Design: Twenty-eight acute myocardial infarction patients with drug-eluting
stent were randomized to either HIT at 85%Y95 % of heart rate reserve or MCT at
70%Y85% of heart rate reserve, 3 days a week for 6 wks at a cardiac rehabilitation
clinic. Primary outcome was VO2peak at baseline and after cardiac rehabilitation.
Results: Both HIT and MCT groups showed significant increases in VO2peak
and heart rate recovery after 6 wks of training. The 22.16% improvement in
VO2peak in the HIT group was significantly greater than the 8.48% improvement in
the MCT group (P = 0.021). There were no cardiovascular events related to both
HIT and MCT.
Conclusions: HIT is more effective than MCT for improving VO2peak in acute
myocardial infarction patients with drug-eluting stent. These findings may have
important implications for more effective exercise training in cardiac rehabilitation
program.
Key Words: Oxygen Consumption, Myocardial Infarction, Exercise, Rehabilitation

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 T here is a growing consensus that exercise has
beneficial effects on patients with cardiovascular
(CV) disease, even on those with severely impaired
cardiac function, and that physical inactivity accel-
erates the severity of heart failure.1 A recent meta-
analysis indicated that cardiac rehabilitation (CR)
programs reduce total and cardiac mortality by
20%Y26% compared with standard medical care.2
Despite the fact that exercise training has become
a central element of CR programs, the amount,
mode, frequency, and intensity of exercise that
yield the best results for these cardiac patients
remain controversial.3
High interval training (HIT) consists of al-
ternating periods of high-intensity aerobic exercise
with periods of passive or active moderate-/mild-
intensity recovery.4 HIT is frequently used in sports
training, and its effects on cardiorespiratory and
muscle systems have led scientists to consider its
application for patients with CV disease.5 Conven-
tional exercise training in patients with coronary
heart disease is of moderate intensity with contin-
uous exercise at 50%Y85% of heart rate reserve
(HRR), but HIT has been considered to be a safe
and more effective method to improve exercise
capacity.5
Peak aerobic exercise capacity, directly mea-
sured as peak oxygen uptake (VO2peak), is the best
predictor of both cardiac and all-cause death
among patients with established CV disease.6 Thus,
it is necessary to identify more effective exercise
programs to increase VO2peak after acute myocar-
dial infarction (AMI). There is a lack of data about
the definite effects and safety of HIT for patients
with AMI who received percutaneous coronary
intervention (PCI) with stent implantation. Pre-
vious studies have found HIT to be more effective
than MCT for improving aerobic capacity in pa-
tients with coronary heart disease.7Y9 However,
most of the studies were done with heterogeneous
patient groups with chronic stable heart disease.
The aim of this study was to compare the effects of
HIT with those of conventional MCT on VO2peak in
AMI patients with drug-eluting stent (DES). The
authors of this study wanted to identify the safety
of HIT for application to patients within 3 wks
after AMI.
METHODS
Subjects
Patients who were admitted to Sanggye Paik
Hospital because of AMI and successfully underwent
880 Kim et al. Am. J. Phys. Med. Rehabil. & Vol. 94, No. 10, October 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
PCI with DES implantation were included. All
subjects were asked to participate in the CR pro-
gram after an explanation on the need for CR and
the program content. The authors enrolled patients
who wanted to participate in the CR program in a
hospital setting. Exclusion criteria included the
left ventricular ejection fraction of less than 30%;
contraindications to vigorous physical activity;
as well as a history of CV disease, cerebrovascular
disease, or pulmonary disease limiting exercise
capacity. Medications did not change during the
6-wk study period. This study was performed
according to the Declaration of Helsinki and was
approved by the regional medical research ethics
committee. Written informed consent was obtained
from all patients. Subject enrollment and flow are
shown in Figure 1.
Exercise Testing
All study subjects received an exercise tolerance
test (ETT) including a baseline test with an average of
17.07 days (HIT group) and 18.57 days (MCT group)
after AMI. Follow-up tests were performed after com-
pleting the 6-wk exercise training. The symptom-
limited ETT was conducted using the modified
Bruce protocol. A real-time recording 12-channel
electrocardiograph (Q4500; Quinton Instrument Co,
Boston, MA), a respiratory gas analyzer (TrueOne
2400 Metabolic Measurement System; ParvoMedics,
Inc, East Sandy, UT), an automatic blood pressure
and pulse monitor (Model 412, Quinton Instru-
ment), as well as a treadmill (Medtrack ST 55,
Quinton Instrument) were used for the ETT. VO2peak
was measured with a respiratory gas analyzer. Peak
heart rate, resting heart rate, and myocardial oxygen
demand (MVO2) were estimated by the electrocar-
diograph as well as the automatic blood pressure
and pulse monitor. MVO2 was calculated by multi-
plying systolic blood pressure and heart rate as
the rate pressure product. Submaximal MVO2 was
measured at the end of stage 3 of the modified
Bruce protocol. Heart rate recovery was defined as
the change in heart rate 1 min after stopping peak
exercise.
Exercise Training
The patients were randomized into either the
HIT or MCT group, and exercise training started
within 3 wks after PCI, three times a week for
6 wks at the hospital, usually with a minimum of
1 wk or three sessions of MCT mode before starting
HIT. The HIT group exercised for a total of 45 mins.
Their program consisted of a 10-min warm-up at
FIGURE 1 Subject enrollment and flow.
50%Y70% of HRR, followed by four times of 4-min
intervals of walking on a treadmill at 85%Y95% of
HRR with three active pauses of 3-min walking
at 50%Y70% of HRR, and a 10-min cooldown at
50%Y70% of HRR. The MCT group exercised for
a total of 45 mins. Their program consisted of
a 10-min warm-up, followed by a 25-min walk on
a treadmill continuously at 70%Y85% of HRR,
and a 10-min cooldown. All training sessions
were supervised by medical staff and monitored
by electrocardiograph, heart rate, blood pressure
using a telemetry monitoring system (Q-Tel RMS,
Cardiac Science, Bothel, WA), and subjective rate
of perceived exertion (RPE). The Borg 6Y20 scale
was used to assess the RPE during and after each
training session. The speed and inclination of
the treadmill were adjusted continuously to en-
sure that every training session was carried out
at the assigned heart rate throughout the train-
ing period.
Blood Sampling
Venous blood was drawn after a 10-hr over-
night fast before and 6 wks after the beginning of
exercise training. The authors analyzed serum
levels of high-density lipoprotein (HDL) choles-
terol, low-density lipoprotein (LDL) cholesterol,
total cholesterol, triglycerides, and high-sensitivity
C-reactive protein (hs-CRP).
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Statistical Analysis
For statistical analysis, the SPSS PC 19.0 ver-
sion was used. When comparing the two groups’
characteristics, if a normal distribution could be
assumed, the authors analyzed changes within
the groups using paired t test. Otherwise, the au-
thors used Wilcoxon’s signed-rank test. They used
Fisher’s exact probability test to compare CV risk
factors, smoking status, and drug history. The
authors did an analysis of covariance to test for
between-group differences in the changes of the
outcome variables from before to after the exercise
training. Intervention group was set as a fixed fac-
tor, and baseline values of the outcome variables
were set as covariates. The tests were two-sided, and
P value less than 0.05 was considered significant.
RESULTS
Twenty-eight subjects successfully completed
6 wks or 18 sessions of CR exercise training, and the
HIT group subjects usually performed a minimum
of 1 wk or three sessions of MCT mode before
starting HIT mode. The HIT group did not show any
statistically significant differences in the RPE score
compared with the MCT group during the HIT
mode. All subjects achieved 85% of HRR within
1 min after increasing exercise intensity from the
intensity of active rest period (50%Y70% of HRR),
and the authors controlled the subjects’ exercise
High Interval Training in Patients with AMI 881
 TABLE 1 Patient characteristics at baseline
HIT (n = 14) MCT (n = 14) P
Male/female 12/2 10/4 0.324
Age, yrs 57 T 11.58 60.2 T 13.64 0.508
BMI, kg/m2 24.28 T 2.93 24.64 T 3.56 0.772
Days after AMI when included 17.07 T 6.02 18.57 T 8.45 0.769
Initial VO2max, mL I kgj1 I minj1 29.15 T 5.46 27.12 T 8.19 0.447
LVEF, % 55.68 T 12.44 51.79 T 12.82 0.423
Hypertension 9 (64%) 9 (64%) 1
Diabetes 1 (7%) 3 (21%) 0.596
Dyslipidemia 9 (64%) 7 (50%) 0.704
Smoking (current/ex/never) 5/5/4 5/5/4 1
Acetylsalicylic acid 14 (100%) 14 (100%) 1
Diuretics 2 (14%) 5 (36%) 0.385
A-Blocker 9 (64%) 11 (79%) 0.678
ACEI/ARB 8 (57%) 12 (86%) 0.209
Statin 14 (100%) 14 (100%) 1
No. diseased vessels
One 9 7
Two 1 4 0.456
Three 4 3
Values are presented as mean T standard deviation or number of patients.
ACEI, angiotensin-1 conversion enzyme inhibitor; ARB, angiotensin-2 receptor blocker. BMI, body mass index; LVEF, left
ventricular ejection fraction.

intensity to maintain the target HR (85%Y95% of
HRR) during the HIT mode. A total of 85.7% of all
HIT time achieved the target HR of HIT.
The distributions of age and sex were similar
between the groups. Subject characteristics including
VO2peak, the left ventricular ejection fraction, CV risk
factors, the number of diseased vessels, and medica-
tion use at baseline were not significantly different
between the groups (Table 1).
Both the HIT and MCT groups showed signifi-
cant increases in VO2peak and heart rate recovery
(Table 2) as well as significant decreases in serum
levels of LDL cholesterol and hs-CRP after 6 wks of
the CR program (Table 3). Only the VO2peak was
significantly different between the two groups.
The 22.16% improvement in VO2peak (from 29.15 T
5.46 to 35.61 T 7.71 mL I kgj1 I minj1) in the HIT
group was significantly greater than the 8.48%
improvement (from 27.12 T 8.19 to 29.59 T 8.65
mL I kgj1 I minj1) in the MCT group (P = 0.021)
(Table 2, Fig. 2). Peak respiratory exchange ratio
was greater than 1.0 in both groups before and after
the 6-wk CR program, and no premature termina-
tion of ETT was observed for any reason. No de-
tectable changes in resting or peak heart rate, body
mass index, serum levels of HDL cholesterol, or

TABLE 2 Outcome variables before and after 6 wks of exercise training

HIT (n = 14) MCT (n = 14)

Baseline Follow-up Baseline Follow-up Pa

Maximal exercise test
VO2peak (mL I kgj1 I minj1) 29.15 T 5.46 35.61 T 7.71b 27.12 T 8.19 29.59 T 8.65b 0.021a
Change of VO2peak, % 22.16 8.48
Peak heart rate, beats per minute 141.4 T 17.6 154.2 T 15.7 144.8 T 20.0 144.9 T 22.6 0.164
Rest heart rate, beats per minute 65.9 T 9.1 67.8 T 11 66.90 T 11.47 64.6 T 6.6 0.21
Heart rate recovery (1 min) 22.57 T5 26.93 T 7.35b 18 T 7.43 23.71 T 7.98b 0.278
Submaximal MVO2 13598 T 3603 12529 T 3319 16187 T 4106 12809 T 3749b 0.885
RER at VO2max 1.12 T 0.15 1.13 T 0.13 1.07 T 0.16 1.15 T 0.16 0.667
Values are presented as mean T standard deviation unless otherwise indicated.
a
HIT vs. MCT (P G 0.05).
b
Baseline vs. follow-up (P G 0.05).
RER, respiratory exchange ratio.

882 Kim et al. Am. J. Phys. Med. Rehabil. & Vol. 94, No. 10, October 2015

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 TABLE 3 Blood markers before and after 6 wks of exercise training
HIT (n = 14) MCT (n = 14)

Baseline Follow-up Baseline Follow-up Pa

HDL, mmol/l 41.21 T 7.55 41.21 T 7.82 38 T 6.79 37.93 T 4.43 0.116
LDL, mmol/l 123.21 T 26.97 76.64 T 25.61b 112.64 T 35.49 82 T 12.15b 0.675
TG, mmol/l 108.07 T 52.49 112.57 T 46.46 104.07 T 59.86 123.86 T 69.96 0.582
hs-CRP 1.21 T 3.17 0.07 T 0.06b 1.78 T 1.75 0.06 T 0.05b 0.685
Values are presented as mean T standard deviation.
a
HIT vs. MCT (P G 0.05).
b
Baseline vs. follow-up (P G 0.05).
TG, triglyceride.

triglycerides were observed in either group after
the training period. No major or minor CV events
were observed during the 6-wk exercise training
periods (total of 378 hrs of exercise) related to both
HIT and MCT (Table 4).
DISCUSSION
HIT offers the possibility of maintaining high-
intensity exercise for longer periods than contin-
uous exercise does.10,11 Therefore, HIT elicits a
greater training stimulus, which further improves
maximal aerobic capacity.12
Although the total exercise time of the two
groups is equal, the HIT group spent 16 mins at
85%Y95% of HRR and the MCT group spent
25 mins at 70%Y85% of HRR. The intensity and
duration of warm-up and cooldown exercise are
equal between the two groups. The authors com-
pared the total work of main exercise performed
by the two groups. The following calculation was
used7: The average VO2peak for all subjects before
the training was 1.89 l/min. The HIT group
performed 4  4-min exercise at 1.6065 l/min
(85% of VO2peak) and 3  3-min exercise at 1.134 l/
min (60% of VO2peak). Thus, the total work of HIT
was 35.91 liter. The MCT group performed 25-min
exercise at 1.4175 l/min (75% of VO2peak). The
total work of MCT was 35.44 liter. The total
amount of work is similar in the two groups.
The main finding of this study was that HIT
was superior to MCT for increasing VO2peak in
the patients with AMI after the DES implantation.
Although VO2peak increased in both groups after
6 weeks of training, the improvement was signif-
icantly greater in the HIT group. Recent HIT
studies targeting patients with coronary heart
disease found a significant increase in VO2peak in
the HIT group compared with that in the MCT
group.7,8 However, the patients with coronary
heart disease came from a wide spectrum in pre-
vious studies: patients who received coronary
artery bypass graft surgery or PCI, those who re-
ceived angiography, and those who had ischemia
during ETT. Furthermore, fewer than 10 patients
were in the HIT and MCT groups.7,8 This study
targeted only the patients with AMI, and every
patient received DES and started HIT early within
17 T 7 days after AMI.
Another strength of this study is that the ex-
ercise period was 6 wks, which is shorter than the

TABLE 4 The corresponding number of

cardiovascular events associated
with HIT and MCT
HIT MCT
Total hours of exercise 189 189
Cardiovascular events
Sudden cardiac death 0 0
Cardiac arrest 0 0
AMI 0 0
Sustained ventricular tachycardia 0 0
Syncope 0 0
Stop by termination criteriaa 0 0
a
Termination criteria: exercise termination criteria by
American Heart Association guideline.
FIGURE 2 VO2peak at baseline and after the 6-wk
training.

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 10Y16 wks in studies previously reporting aerobic
interval training. In this short-term HIT, which
targeted patients with AMI and DES, VO2peak in-
creased significantly compared with MCT. Guiraud
et al.13 showed that a single HIT session may have
immediate beneficial effects on the endothelium.
Other studies have shown that, in a relatively short
timeframe (8 wks), intermittent ischemia induced
by HIT fosters the formation of collateral coronary
vessels in animal models without causing myocar-
dial injury.14
All 28 subjects in the two groups used ator-
vastatin, and the average dose taken by each sub-
ject in each group was 16.4 mg in the HCT group
and 17.1 mg in the MCT group; there was no
statistically significant difference. Both groups
showed significant decreases in serum LDL cho-
lesterol and hs-CRP levels 6 wks after the exercise
training, but no significant differences were ob-
served between the two groups. No significant
differences in serum HDL cholesterol or triglyc-
eride levels were observed before or after the ex-
ercise training, and no differences were detected
between the two groups. In previous studies, less
than 8 wks of aerobic interval training did not
show any significant change in HDL cholesterol;
at least 8 wks were required to bring a significant
increase.15Y17 In addition, exercise of medium or
high intensity elicits increases in HDL cholesterol
but does not improve LDL cholesterol or tri-
glycerides.18 Therefore, no changes in HDL cho-
lesterol or triglycerides were observed, likely
owing to the short 6-wk duration of the program,
and the changes in LDL cholesterol and hs-CRP
were likely a result of the statin that the patients
in both groups were newly prescribed after the
AMI event.
A review article of HIT in a CR program showed
that no significant clinical, hemodynamic, electric,
or biologic signs of ischemia or arrhythmia are
observed with HIT.5 Although this study targeted
patients with acute disease within an average of
3 wks of disease occurrence and those who received
a DES, not a single case of emergency, such as
cardiac arrest, sudden cardiac death, AMI, ventric-
ular tachycardia, or syncope caused by HIT, oc-
curred during the 378 hrs of exercise, so HIT is
not dangerous for patients with AMI. This result
shows that, when the specific HIT method is based
on each patient’s evaluation and when it is moni-
tored according to his/her exercise risk, it is safe. In
addition, when cardiac resuscitation is performed
immediately by a cardiac specialist, mortality rate
can be decreased six times,19 so it is desirable to
884 Kim et al. Am. J. Phys. Med. Rehabil. & Vol. 94, No. 10, October 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
carry out HIT in an environment where patient
status can be monitored continuously.
The submaximal MVO2 did not change by a
greater amount in HIT compared with MCT. The
authors also had questions on why such results
came out, and they still cannot explain it clearly.
However, although it was not statistically signifi-
cant, baseline MVO2 was higher in the MCT group
(P = 0.075). MVO2 after the training was similar
between the two groups (P = 0.885). Thus, only
in MCT group was there a significant decrease
in MVO2. In addition, another cause may be
that, although it was not statistically significant,
more subjects were taking A-blockers in the MCT
group (79%).
Because the intensity of exercise changes re-
peatedly during HIT, the exercise is less boring, and
HIT has the potential to improve exercise adher-
ence.20,21 Therefore, HIT is more effective than
MCT in motivating patients to exercise.22 However,
despite the effect of motivation, the time burden of
participating in an exercise program at a hospital
for a certain period remains a critical factor in de-
creased exercise training participation.23 It has
been reported that less than 50% of patients par-
ticipate in an exercise training program for more
than 6 mos.24 Therefore, short-term HIT can in-
crease participation in CR programs, enable pa-
tients to reach high levels of exercise capacity in a
short time, and sustain the exercise habit in their
daily lives.
Dyspnea and fatigue are major factors that
prevent exercise. However, HIT can increase pa-
tient tolerance and allow them to exercise fully
until exhaustion because of the passive/active re-
covery phase in between high-intensity exercises in
patients who do not like to exercise intensely, pa-
tients who have lung disease with dyspnea, patients
with heart failure and ischemic heart disease, older
patients, as well as patients with low exercise ca-
pacity. In a study by Guiraud et al.,25 the cardio-
pulmonary and biologic responses induced by HIT
were compared with those induced by an isocaloric
MCT session. Efficiency (energy expenditure/effort
time) and tolerance (ability to complete exercise
sessions, ventilation) were all greater with HIT
relative to MCT. In addition, patients subjectively
preferred the optimized HIT session, which was
associated with a lower RPE compared with that of
MCT. Furthermore, HIT produced a substantial
physiologic stimulus, time spent at an intensity
greater than 90% of VO2peak, and central hemody-
namic responses were similar to those induced by
MCT.26 Obese, female patients generally preferred
HIT to MCT, which may also be a reflection of the
less-intense sensation of dyspnea, because mean
ventilation was far lower, whereas the difference
in mean VO2peak, even though significant, was
relatively small.27 Therefore, this protocol could
be particularly useful for weight loss in overweight
and obese individuals for whom continuous
moderate-intensity exercise may be limited by
fatigue and dyspnea.
The limitation of this study was that, because
the observation period was only 6 wks, long-term
follow-up investigations could not be done. When
HIT is conducted clinically and exercise is contin-
ued at home based on HIT, it is difficult to maintain
exercise intensity, so no significant difference in
VO2peak is observed between HIT and MCT in the
long term.9 Therefore, it is necessary to determine
whether the HIT group maintains a significantly
higher VO2peak compared with the MCT group when
the exercise method is managed periodically.
Second, HRR was used to determine exercise in-
tensity. Although using HRR to prescribe exercise
intensity is valid,9 if a patient has arrhythmia or is
taking A-blockers, heart rate may not be a good
reflection of exertion level. Another study indicated
that, for patients who changed the amount of
A-blocker, using heart rate to determine exer-
cise intensity may not be valid.28 In this study,
the amount of A-blocker was maintained con-
sistently during the 6 wks of exercise training,
and none of the patients changed. In addition,
no patient with arrhythmia, which could affect
the heart rate measurement, was included. How-
ever, because most patients take A-blockers, not
only heart rate but also RPE should be used when
determining exercise intensity for these patients.
Third, because the number of patients was low,
even though there was no incidence of side effects
or complications, it is difficult to conclude that HIT
is sufficiently safe. Therefore, larger studies with
more patients must be conducted to conclude that
HIT is effective and safe in the long term.
CONCLUSIONS
The authors confirmed that HIT is safe and
effective in patients with AMI who underwent PCI
with DES. In addition, the authors confirmed that
exercise intensity is important for improving aer-
obic capacity because VO2peak increased signifi-
cantly compared with that in the MCT group. The
authors believe that these results can help change
the intensity of CR exercise training programs
as well as improve patient exercise capacity and
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quality-of-life. This research should be expanded
to patients with chronic heart failure or those
who underwent coronary artery bypass graft so
that wide clinical application of HIT can be better
understood. Additional research on higher in-
tensity and short interval training with more
patients who can be followed in longer periods
needs to be done.
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