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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 ORIGINAL RESEARCH ARTICLE
Paik Hospital, Inje University College of
Medicine, Seoul (CK, MHL); and
Department of Physical Medicine and
Rehabilitation, Haeundae Paik
Hospital, Inje University College of Effect of High Interval Training in
Medicine, Busan, South Korea (HEC).
Acute Myocardial Infarction Patients
Correspondence:
All correspondence and requests for
with Drug-Eluting Stent
reprints should be addressed to: Hee
Eun Choi, MD, Department of Physical
Medicine and Rehabilitation, Haeundae
Paik Hospital, Inje University College of ABSTRACT
Medicine, 875 Haeun-daero, Kim C, Choi HE, Lim MH: Effect of high interval training in acute myocardial
Haeundae-gu, Busan, South Korea.
infarction patients with drug-eluting stent. Am J Phys Med Rehabil
2015;94:879Y886.
Disclosures:
Financial disclosure statements have Objective: Peak oxygen uptake (VO2peak) is a strong predictor of survival in
been obtained, and no conflicts of cardiac patients. The aims of this study were to compare the effects of high interval
interest have been reported by the training (HIT) to moderate continuous training (MCT) on VO2peak and to identify
authors or by any individuals in control
of the content of this article. the safety of HIT in acute myocardial infarction patients with drug-eluting stent.
Design: Twenty-eight acute myocardial infarction patients with drug-eluting
0894-9115/15/9410-0879 stent were randomized to either HIT at 85%Y95 % of heart rate reserve or MCT at
American Journal of Physical 70%Y85% of heart rate reserve, 3 days a week for 6 wks at a cardiac rehabilitation
Medicine & Rehabilitation clinic. Primary outcome was VO2peak at baseline and after cardiac rehabilitation.
Copyright * 2015 Wolters Kluwer
Health, Inc. All rights reserved. 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
DOI: 10.1097/PHM.0000000000000290
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
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
(CV) disease, even on those with severely impaired the program content. The authors enrolled patients
cardiac function, and that physical inactivity accel- who wanted to participate in the CR program in a
erates the severity of heart failure.1 A recent meta- hospital setting. Exclusion criteria included the
analysis indicated that cardiac rehabilitation (CR) left ventricular ejection fraction of less than 30%;
programs reduce total and cardiac mortality by contraindications to vigorous physical activity;
20%Y26% compared with standard medical care.2 as well as a history of CV disease, cerebrovascular
Despite the fact that exercise training has become disease, or pulmonary disease limiting exercise
a central element of CR programs, the amount, capacity. Medications did not change during the
mode, frequency, and intensity of exercise that 6-wk study period. This study was performed
yield the best results for these cardiac patients according to the Declaration of Helsinki and was
remain controversial.3 approved by the regional medical research ethics
High interval training (HIT) consists of al- committee. Written informed consent was obtained
ternating periods of high-intensity aerobic exercise from all patients. Subject enrollment and flow are
with periods of passive or active moderate-/mild- shown in Figure 1.
intensity recovery.4 HIT is frequently used in sports
training, and its effects on cardiorespiratory and Exercise Testing
muscle systems have led scientists to consider its
All study subjects received an exercise tolerance
application for patients with CV disease.5 Conven-
test (ETT) including a baseline test with an average of
tional exercise training in patients with coronary
17.07 days (HIT group) and 18.57 days (MCT group)
heart disease is of moderate intensity with contin-
after AMI. Follow-up tests were performed after com-
uous exercise at 50%Y85% of heart rate reserve
pleting the 6-wk exercise training. The symptom-
(HRR), but HIT has been considered to be a safe
limited ETT was conducted using the modified
and more effective method to improve exercise
Bruce protocol. A real-time recording 12-channel
capacity.5
electrocardiograph (Q4500; Quinton Instrument Co,
Peak aerobic exercise capacity, directly mea-
Boston, MA), a respiratory gas analyzer (TrueOne
sured as peak oxygen uptake (VO2peak), is the best
2400 Metabolic Measurement System; ParvoMedics,
predictor of both cardiac and all-cause death
Inc, East Sandy, UT), an automatic blood pressure
among patients with established CV disease.6 Thus,
and pulse monitor (Model 412, Quinton Instru-
it is necessary to identify more effective exercise
ment), as well as a treadmill (Medtrack ST 55,
programs to increase VO2peak after acute myocar-
Quinton Instrument) were used for the ETT. VO2peak
dial infarction (AMI). There is a lack of data about
was measured with a respiratory gas analyzer. Peak
the definite effects and safety of HIT for patients
heart rate, resting heart rate, and myocardial oxygen
with AMI who received percutaneous coronary
demand (MVO2) were estimated by the electrocar-
intervention (PCI) with stent implantation. Pre-
diograph as well as the automatic blood pressure
vious studies have found HIT to be more effective
and pulse monitor. MVO2 was calculated by multi-
than MCT for improving aerobic capacity in pa-
plying systolic blood pressure and heart rate as
tients with coronary heart disease.7Y9 However,
the rate pressure product. Submaximal MVO2 was
most of the studies were done with heterogeneous
measured at the end of stage 3 of the modified
patient groups with chronic stable heart disease.
Bruce protocol. Heart rate recovery was defined as
The aim of this study was to compare the effects of
the change in heart rate 1 min after stopping peak
HIT with those of conventional MCT on VO2peak in
exercise.
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 Exercise Training
after AMI. The patients were randomized into either the
HIT or MCT group, and exercise training started
METHODS within 3 wks after PCI, three times a week for
6 wks at the hospital, usually with a minimum of
Subjects 1 wk or three sessions of MCT mode before starting
Patients who were admitted to Sanggye Paik HIT. The HIT group exercised for a total of 45 mins.
Hospital because of AMI and successfully underwent Their program consisted of a 10-min warm-up at

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

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


FIGURE 1 Subject enrollment and flow.

50%Y70% of HRR, followed by four times of 4-min Statistical Analysis


intervals of walking on a treadmill at 85%Y95% of For statistical analysis, the SPSS PC 19.0 ver-
HRR with three active pauses of 3-min walking sion was used. When comparing the two groups’
at 50%Y70% of HRR, and a 10-min cooldown at characteristics, if a normal distribution could be
50%Y70% of HRR. The MCT group exercised for assumed, the authors analyzed changes within
a total of 45 mins. Their program consisted of the groups using paired t test. Otherwise, the au-
a 10-min warm-up, followed by a 25-min walk on thors used Wilcoxon’s signed-rank test. They used
a treadmill continuously at 70%Y85% of HRR, Fisher’s exact probability test to compare CV risk
and a 10-min cooldown. All training sessions factors, smoking status, and drug history. The
were supervised by medical staff and monitored authors did an analysis of covariance to test for
by electrocardiograph, heart rate, blood pressure between-group differences in the changes of the
using a telemetry monitoring system (Q-Tel RMS, outcome variables from before to after the exercise
Cardiac Science, Bothel, WA), and subjective rate training. Intervention group was set as a fixed fac-
of perceived exertion (RPE). The Borg 6Y20 scale tor, and baseline values of the outcome variables
was used to assess the RPE during and after each were set as covariates. The tests were two-sided, and
training session. The speed and inclination of P value less than 0.05 was considered significant.
the treadmill were adjusted continuously to en-
sure that every training session was carried out
at the assigned heart rate throughout the train- RESULTS
ing period. Twenty-eight subjects successfully completed
6 wks or 18 sessions of CR exercise training, and the
HIT group subjects usually performed a minimum
Blood Sampling of 1 wk or three sessions of MCT mode before
Venous blood was drawn after a 10-hr over- starting HIT mode. The HIT group did not show any
night fast before and 6 wks after the beginning of statistically significant differences in the RPE score
exercise training. The authors analyzed serum compared with the MCT group during the HIT
levels of high-density lipoprotein (HDL) choles- mode. All subjects achieved 85% of HRR within
terol, low-density lipoprotein (LDL) cholesterol, 1 min after increasing exercise intensity from the
total cholesterol, triglycerides, and high-sensitivity intensity of active rest period (50%Y70% of HRR),
C-reactive protein (hs-CRP). and the authors controlled the subjects’ exercise

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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 the CR program (Table 3). Only the VO2peak was
HRR) during the HIT mode. A total of 85.7% of all significantly different between the two groups.
HIT time achieved the target HR of HIT. The 22.16% improvement in VO2peak (from 29.15 T
The distributions of age and sex were similar 5.46 to 35.61 T 7.71 mL I kgj1 I minj1) in the HIT
between the groups. Subject characteristics including group was significantly greater than the 8.48%
VO2peak, the left ventricular ejection fraction, CV risk improvement (from 27.12 T 8.19 to 29.59 T 8.65
factors, the number of diseased vessels, and medica- mL I kgj1 I minj1) in the MCT group (P = 0.021)
tion use at baseline were not significantly different (Table 2, Fig. 2). Peak respiratory exchange ratio
between the groups (Table 1). was greater than 1.0 in both groups before and after
Both the HIT and MCT groups showed signifi- the 6-wk CR program, and no premature termina-
cant increases in VO2peak and heart rate recovery tion of ETT was observed for any reason. No de-
(Table 2) as well as significant decreases in serum tectable changes in resting or peak heart rate, body
levels of LDL cholesterol and hs-CRP after 6 wks of 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 was 35.91 liter. The MCT group performed 25-min
the training period. No major or minor CV events exercise at 1.4175 l/min (75% of VO2peak). The
were observed during the 6-wk exercise training total work of MCT was 35.44 liter. The total
periods (total of 378 hrs of exercise) related to both amount of work is similar in the two groups.
HIT and MCT (Table 4). The main finding of this study was that HIT
was superior to MCT for increasing VO2peak in
DISCUSSION the patients with AMI after the DES implantation.
HIT offers the possibility of maintaining high- Although VO2peak increased in both groups after
intensity exercise for longer periods than contin- 6 weeks of training, the improvement was signif-
uous exercise does.10,11 Therefore, HIT elicits a icantly greater in the HIT group. Recent HIT
greater training stimulus, which further improves studies targeting patients with coronary heart
maximal aerobic capacity.12 disease found a significant increase in VO2peak in
Although the total exercise time of the two the HIT group compared with that in the MCT
groups is equal, the HIT group spent 16 mins at group.7,8 However, the patients with coronary
85%Y95% of HRR and the MCT group spent heart disease came from a wide spectrum in pre-
25 mins at 70%Y85% of HRR. The intensity and vious studies: patients who received coronary
duration of warm-up and cooldown exercise are artery bypass graft surgery or PCI, those who re-
equal between the two groups. The authors com- ceived angiography, and those who had ischemia
pared the total work of main exercise performed during ETT. Furthermore, fewer than 10 patients
by the two groups. The following calculation was were in the HIT and MCT groups.7,8 This study
used7: The average VO2peak for all subjects before targeted only the patients with AMI, and every
the training was 1.89 l/min. The HIT group patient received DES and started HIT early within
performed 4  4-min exercise at 1.6065 l/min 17 T 7 days after AMI.
(85% of VO2peak) and 3  3-min exercise at 1.134 l/ Another strength of this study is that the ex-
min (60% of VO2peak). Thus, the total work of HIT 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 carry out HIT in an environment where patient
interval training. In this short-term HIT, which status can be monitored continuously.
targeted patients with AMI and DES, VO2peak in- The submaximal MVO2 did not change by a
creased significantly compared with MCT. Guiraud greater amount in HIT compared with MCT. The
et al.13 showed that a single HIT session may have authors also had questions on why such results
immediate beneficial effects on the endothelium. came out, and they still cannot explain it clearly.
Other studies have shown that, in a relatively short However, although it was not statistically signifi-
timeframe (8 wks), intermittent ischemia induced cant, baseline MVO2 was higher in the MCT group
by HIT fosters the formation of collateral coronary (P = 0.075). MVO2 after the training was similar
vessels in animal models without causing myocar- between the two groups (P = 0.885). Thus, only
dial injury.14 in MCT group was there a significant decrease
All 28 subjects in the two groups used ator- in MVO2. In addition, another cause may be
vastatin, and the average dose taken by each sub- that, although it was not statistically significant,
ject in each group was 16.4 mg in the HCT group more subjects were taking A-blockers in the MCT
and 17.1 mg in the MCT group; there was no group (79%).
statistically significant difference. Both groups Because the intensity of exercise changes re-
showed significant decreases in serum LDL cho- peatedly during HIT, the exercise is less boring, and
lesterol and hs-CRP levels 6 wks after the exercise HIT has the potential to improve exercise adher-
training, but no significant differences were ob- ence.20,21 Therefore, HIT is more effective than
served between the two groups. No significant MCT in motivating patients to exercise.22 However,
differences in serum HDL cholesterol or triglyc- despite the effect of motivation, the time burden of
eride levels were observed before or after the ex- participating in an exercise program at a hospital
ercise training, and no differences were detected for a certain period remains a critical factor in de-
between the two groups. In previous studies, less creased exercise training participation.23 It has
than 8 wks of aerobic interval training did not been reported that less than 50% of patients par-
show any significant change in HDL cholesterol; ticipate in an exercise training program for more
at least 8 wks were required to bring a significant than 6 mos.24 Therefore, short-term HIT can in-
increase.15Y17 In addition, exercise of medium or crease participation in CR programs, enable pa-
high intensity elicits increases in HDL cholesterol tients to reach high levels of exercise capacity in a
but does not improve LDL cholesterol or tri- short time, and sustain the exercise habit in their
glycerides.18 Therefore, no changes in HDL cho- daily lives.
lesterol or triglycerides were observed, likely Dyspnea and fatigue are major factors that
owing to the short 6-wk duration of the program, prevent exercise. However, HIT can increase pa-
and the changes in LDL cholesterol and hs-CRP tient tolerance and allow them to exercise fully
were likely a result of the statin that the patients until exhaustion because of the passive/active re-
in both groups were newly prescribed after the covery phase in between high-intensity exercises in
AMI event. patients who do not like to exercise intensely, pa-
A review article of HIT in a CR program showed tients who have lung disease with dyspnea, patients
that no significant clinical, hemodynamic, electric, with heart failure and ischemic heart disease, older
or biologic signs of ischemia or arrhythmia are patients, as well as patients with low exercise ca-
observed with HIT.5 Although this study targeted pacity. In a study by Guiraud et al.,25 the cardio-
patients with acute disease within an average of pulmonary and biologic responses induced by HIT
3 wks of disease occurrence and those who received were compared with those induced by an isocaloric
a DES, not a single case of emergency, such as MCT session. Efficiency (energy expenditure/effort
cardiac arrest, sudden cardiac death, AMI, ventric- time) and tolerance (ability to complete exercise
ular tachycardia, or syncope caused by HIT, oc- sessions, ventilation) were all greater with HIT
curred during the 378 hrs of exercise, so HIT is relative to MCT. In addition, patients subjectively
not dangerous for patients with AMI. This result preferred the optimized HIT session, which was
shows that, when the specific HIT method is based associated with a lower RPE compared with that of
on each patient’s evaluation and when it is moni- MCT. Furthermore, HIT produced a substantial
tored according to his/her exercise risk, it is safe. In physiologic stimulus, time spent at an intensity
addition, when cardiac resuscitation is performed greater than 90% of VO2peak, and central hemody-
immediately by a cardiac specialist, mortality rate namic responses were similar to those induced by
can be decreased six times,19 so it is desirable to MCT.26 Obese, female patients generally preferred

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

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


HIT to MCT, which may also be a reflection of the quality-of-life. This research should be expanded
less-intense sensation of dyspnea, because mean to patients with chronic heart failure or those
ventilation was far lower, whereas the difference who underwent coronary artery bypass graft so
in mean VO2peak, even though significant, was that wide clinical application of HIT can be better
relatively small.27 Therefore, this protocol could understood. Additional research on higher in-
be particularly useful for weight loss in overweight tensity and short interval training with more
and obese individuals for whom continuous patients who can be followed in longer periods
moderate-intensity exercise may be limited by needs to be done.
fatigue and dyspnea.
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