The effect of high-intensity aerobic interval training on postinfarction left ventricular remodelling

Article (PDF Available)inBMJ Case Reports 2013(feb13 1) · February 2013with218 Reads
DOI: 10.1136/bcr-2012-007668 · Source: PubMed
Abstract
This is the third in a series of case studies on an individual with normal coronaries who sustained an idiopathic acute myocardial infarction . Bilateral pulmonary emboli almost 2 years post-myocardial infarction (MI) revealed coagulopathy as the cause. The original MI resulted in 16% myocardial scar tissue. An increasing number of patients are surviving MI, hence the burden for healthcare often shifts to heart failure. Accumulating evidence suggests high-intensity aerobic interval exercise (AHIT) is efficacious in improving cardiac function in health and disease. However, its impact on MI scar has never been assessed. Accordingly, the 50-year-old subject of this case study undertook 60 weeks of regular AHIT. Successive cardiac MRI results demonstrate, for the first time, a decrease in MI scar with exercise and, alongside mounting evidence of high efficacy and low risk, suggests AHIT may be increasingly important in future prevention and reversing of disease and or amelioration of symptoms.

Figures

CASE REPORT
The effect of high-intensity aerobic interval training
on postinfarction left ventricular remodelling
Richard Godfrey,
1
Thomas Theologou,
2,3,4
Santo Dellegrottaglie,
5
Sukumaran Binukrishnan,
2
Jay Wright,
3
Gregory Whyte,
6
Georgina Ellison
3,4,6
1
Centre for Sports Medicine
and Human Performance,
School of Sport and Education,
Brunel University, Uxbridge, UK
2
Department of Cardiology and
Radiology, The Liverpool Heart
and Chest Hospital, Liverpool,
UK
3
Institute of Cardiovascular
Medicine and Science, The
Liverpool Heart & Chest
Hospital, Thomas Drive,
Liverpool, UK
4
Stem Cell & Regenerative
Biology Unit (BioStem),
Research Institute for Sport &
Exercise Sciences, Liverpool
John Moores University,
Liverpool, UK
5
Division of Cardiology,
Ospedale Medico-Chirurgico
Accreditato Villa dei Fiori,
Naples, Italy
6
Cardiovascular Physiology
Unit, Research Institute for
Sport and Exercise Sciences,
Liverpool John Moores
University, Liverpool, UK
Correspondence to
Dr Richard Godfrey,
richard.godfrey@brunel.ac.uk
To cite: Godfrey R,
Theologou T,
Dellegrottaglie S, et al. BMJ
Case Rep Published online:
[please include Day Month
Year] doi:10.1136/bcr-2012-
007668
SUMMARY
This is the third in a series of case studies on an
individual with normal coronaries who sustained an
idiopathic acute myocardial infarction . Bilateral
pulmonary emboli almost 2 years post-myocardial
infarction (MI) revealed coagulopathy as the cause. The
original MI resulted in 16% myocardial scar tissue. An
increasing number of patients are surviving MI, hence
the burden for healthcare often shifts to heart failure.
Accumulating evidence suggests high-intensity aerobic
interval exercise (AHIT) is efcacious in improving cardi ac
function in health and disease. However, its impact on
MI scar has never been assessed. Accordingly, the 50-
year-old subject of this case study undertook 60 weeks
of regular AHIT. Successive cardiac MRI results
demonstrate, for the rst time, a decrease in MI scar
with exercise and, alongside mounting eviden ce of high
efcacy and low risk, suggests AHIT may be increasingly
important in future prevention and reversing of disease
and or amelioration of symptoms.
BACKGROUND
Myocardial infarction (MI) is usually the consequence
of acute cardiac muscle ischaemia downstream of a
blockage in the coronary vasculatur e. The resulting
myocardial scar tissue has traditionally been consid-
ered to be inert and permanent, perhaps a logical
assumption for a pos tmitotic organ such as the heart.
That view is increasingly being challenged however,
and it has been sugges ted tha t the heart of patients
surviving MI may demonstrate some potential for
regener a tion.
1
Cardiomyocytes of the adult mammalian myo-
cardium are terminally differentiated cells that are
permanently withdrawn from the cell cycle.
23
Thus, the adult heart is composed of a large mass
of postmitotic cells, but, nevertheless, it has a
remarkable capacity for regeneration, both under
normal conditions
4
and in response to diverse
pathological
56
and physiological stimuli, including
aerobic exercise training.
79
The potential for
regeneration is ensured by the presence of
endogenous tissue-specic cardiac stem-progenitor
cells.
10 11
Elucidation of the molecular signalling
pathways that govern myocardial regeneration and
repair, and a better understanding of endogenous
cardiac stem cell biology will allow the design of
optimal therapeutic interventions.
During the last decade, a growing body of evi-
dence has demonstrated the efcacy of high-
intensity interval training (HIT) in general, and of
aerobic HIT (AHIT) specically, in the treatment
and prevention of a number of pathologies.
12
HIT
(ie, maximal anaerobic and aerobic interval training
at greater than 85% of maximum heart rate, HRM)
has been demonstrated to be more effective than
moderate or low-intensity exercise for improving
health status. Several parameters have seen positive
change with the implementation of HIT including:
improved insulin sensitivity in patients with type II
diabetes,
13
improved lipid proles,
14
and improved
VO
2max
, the generic marker of aerobic conditioning
which is inversely related to all-cause morbidity
and mortality.
15 16
A number of studies have demonstrated the bene-
ts of starting exercise rehabilitation soon after
MI in order to prevent remodelling rather than
having to reverse-remodel following a delay in the
onset of a cardiac rehabilitation programme.
1719
Accordingly, exercise has been demonstrated as
being not only positive, but also essential to the
recovery process and the prevention of further
disease or deterioration in function.
Recent experimental studies have used a rodent
model of MI to evaluate the effects of AHIT typic-
ally involving repeated intervals of 8 min of exer-
cise at an intensity that elicits >90% of HRM
with 3 min of active recovery between each work
interval. In a sample of eight studies that have been
carried out on rodents, no coronary events or
deaths have resulted from AHIT (U Wisloff, O
Kemi, J Helgerud, J Talanian and O Ellingsen, per-
sonal communication, March 2011). Human parti-
cipants have in general performed AHIT
comprising 4 min intervals with 3 min recoveries.
Using this paradigm, a recent study of 4846 coron-
ary heart disease patients, in Norway, with a range
of diagnoses including coronary artery disease, con-
gestive heart failure, metabolic syndrome, hyper-
tension, obesity and older age, were exercised
either at a high-intensity or moderate-intensity. Of
a total of 175 820 exercise training hours, where
all patients performed both types of training, there
was one fatal cardiac arrest during
moderate-intensity exercise (129 456 exercise
hours) and two non-fatal cardiac arrests during
high-intensity interval exercise (46 364 exercise
hours). Overall, there were no MIs, concluding that
the risk of a cardiovascular event is low after both
high-intensity and moderate-intensity exercise in a
cardiovascular rehabilitation setting.
20
Moreover,
Herman et al
21
examined the effect of interval
training for 8 weeks with daily intervals of greater
than 85% of HRM in long-term heart transplant
recipients and reported no serious adverse events.
Godfrey R, et al. BMJ Case Rep 2013. doi:10.1136/bcr-2012-007668 1
Novel treatment (new drug/intervention; established drug/procedure in new situation)
In practice, AHIT involves exercise utilising a number of
short duration efforts (14 min) at a relatively high exercise
intensity (ie, >90% of HRM) and with short rest intervals of
30 s3 min. The use of this type of exercise training in patients
with a prior MI, in the presence of ventricular damage, is
uncommon particularly in the UK. This is, presumably, because
of the perception of risk; however, there is no empirical evi-
dence that AHIT is more risky than moderate-intensity or
low-intensity exercise. Furthermore, many clinicians are simply
unaware of the positive benets to health to be accrued through
regular AHIT.
Therefore, the aim of this work was to implement a
12-month AHIT intervention in a single individual who had
previously sustained an MI and, using cardiac MRI (cMRI),
assess any changes in the extent of MI scar, left ventricular (LV)
systolic function, viability and diastolic compliance. If AHIT
provides a stimulus for improved LV remodelling then this will
be the rst time that the efcacy of high-intensity exercise will
have been demonstrated for myocardial repair and may provide
a platform for the investigation of AHIT as a therapeutic inter-
vention in MI patients.
CASE PRESENTATION
The patient is a 50-year-old man of mixed race (Caucasian
mother, Indian father) with a 35-year history of extensive and
intensive physical activity. In September 2007, the patient suf-
fered an MI at the age of 45 years.
22
The underlying cause of
the original MI remained unknown for just under 2 years until,
following almost 3 months of breathlessness and dizziness, the
patient was admitted to A&E with a deep vein thrombosis and
bilateral pulmonary emboli ( July 2009). Follow-up investigation
resulted in a consensus, non-denitive, diagnosis of coagulopa-
thy.
23
cMRI 14 months post-acute myocardial infarction (AMI)
demonstrated ischaemic scar involving the mid and basal
segments of the inferior wall, amounting to 16.3% of total LV
myocardial mass.
INVESTIGATIONS
Three separated cMRI studies: study 1, performed 14 months
after AMI (when spontaneous LV remodelling can be considered
complete); study 2, obtained after 14 weeks of AHIT and
study 3, acquired after a total of 60 weeks of AHIT. The cMRI
protocol included a full set of cine images to assess LV function
and delayed postcontrast images for scar evaluation.
In May and August 2011 and March 2012, maximal aerobic
power (VO
2
max) was assessed on a cycle ergometer (Excalibur
Sport, Lode Gronigen, the Netherlands) with ergospirometry
(Quark b
2
, Cosmed, Rome, Italy).
TREATMENT
Between January 2011 and March 2012, the patient voluntarily
undertook AHIT which included sets of up to 20×(1 min hard
followed by 1 min easy); 6×(2 min hard followed by 2 min
easy); 4×(4 min hard followed by 2 min easy) on an exercise
bike 24 times/week. All sessions elicited a heart rate >90%
HRM in each interval and, for several intervals per session, a
heart rate >95% of maximum was elicited. The number and
volume of sessions of monthly AHIT for the 14-month inter-
vention period is given in table 1.
In addition to the intervention described above, it should be
noted that, throughout this period, the patient was subject to
the following daily medication: 75 mg aspirin, 20 mg simvasta-
tin and 5 mg warfarin.
OUTCOME AND FOLLOW-UP
The initial cMRI scan demonstrated an ischaemic scar involving
the mid and basal segments of the inferior wall, amounting to
16.3% of total LV myocardial mass. A progressive decrease in
scar tissue was noted from successive cMRIs: 9.6% in study 2
and 8.5% of LV myocardial mass in study 3. This represents
almost a 50% scar reduction following long-term AHIT
(gure 1). The relative reduction in scar size is, at least in part,
related to an increase in LV mass after AHIT (from 152 to 153 g,
and then 162 g from studies 1 to 3, respectively). However, the
greatest reduction in scar size (40%) occurred between studies
1 and 2 (after 14 weeks of AHIT) when the LV mass remained
unchanged. Cine images from repeated cMRI did not demon-
strate clinically meaningful changes in LV systolic and diastolic
function, ejection fraction or peak lling rate (table 2).
In May, VO
2max
was 34 ml/kg/min; in August, it was
38 ml/kg/min and in March 2012, it was 43 ml/kg/min. This
Table 1 Number and volume of sessions of aerobic high-intensity interval training(AHIT) per month
Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Dec Feb
AHIT (no) 12 8 15 13 6 8 14 9 6 10 6 7 6 9
AHIT (min) 410 285 410 474 220 254 563 280 185 285 245 272 240 366
Figure 1 Representative cardiac MRI
images of the evolution of the
myocardial scar, involving the basal
segment of the inferior left ventricular
wall, from study 1 (14 months after
acute myocardial infarction) to study 2
(14 weeks after aerobic high-intensity
interval training (AHIT) to study 3
(60 weeks after AHIT).
2 Godfrey R, et al. BMJ Case Rep 2013. doi:10.1136/bcr-2012-007668
Novel treatment (new drug/intervention; established drug/procedure in new situation)
demonstrates a 26% increase in aerobic power over the course
of a year of AHIT.
DISCUSSION
The results of this single individual case study show that
14 weeks of AHIT resulted in 40% reduction of the MI scar,
which was improved as evidenced by 50% reduction following
60 weeks of AHIT. To date a reduction in MI scar as a result of
physical training has never been reported in humans or indeed
any animal model. This case study is the rst to demonstrate a
reduction in MI scar tissue in response to high-intensity exercise
and so may act as a valuable tool in treatment of the post-MI
patient.
Exercise training activates circulating stem-progenitor cells
24
as well as the resident tissue-specic cardiac stem-progenitor
cells.
8
We have previously reported an increased proliferation,
number and cardiogenic differentiation of the resident endogen-
ous cardiac stem-progenitor cells with physiological overload in
the form of swimming and intensity-controlled treadmill endur-
ance exercise training.
89
This, in turn, leads to the accumula-
tion of new myocardial cells, namely, new myocytes and
microvasculature.
79
These cellular modications are dependent
on exercise duration and intensity and result in increased con-
tractile muscle mass and enhanced cardiac function, which
reduces myocardial wall stress.
9
Moreover, we have shown that
intracoronary administration of the growth factors, IGF-1 and
HGF, which are typically upregulated with physiological over-
load,
89
to the infarcted pig heart can reduce pathological
remodelling and brosis and trigger a regenerative response of
the resident endogenous cardiac stem-progenitor cells, leading
to decreased scar size and improved ventricular function.
25
Whether this individuals three-and-a-half decade history of
intensive and extensive exercise is relevant to the outcome is
unknown but that it may have contributed cannot be ruled out.
In addition, AHIT requires signicant determination to complete
even a single session as it represents a signicant challenge both
physically and psychologically. Whether it would be possible to
achieve such a level of physical activity with the previously
sedentary, or even those who currently take part in moderate-
intensity exercise, is also unknown.
Limitations of this study include: ndings are from only a
single individual, and cMRI was not used immediately before
start of exercise intervention and, hence, spontaneous resolution
cannot be discounted. However, this has never been recorded
before and so, seems unlikely. Accordingly, the nding in this
current case study, coupled with the very low incidence of
adverse events culled from previous studies, suggests the need
for a prospective study of a population of MI patients undertak-
ing AHIT to conrm any effect on MI scar and myocardial
compliance. Future research should aim to provide further evi-
dence for the efcacy of AHIT in improving cardiac perform-
ance and to examine the safety of such training.
Learning points
High-intensity aerobic interval training may reduce scar
post-acute myocardial infarction and may reduce the risks
of subsequent development of heart failure.
High-intensity aerobic interval training has been
demonstrated to improve cardiac function in the healthy but
also for many with disease, including heart disease.
There is no empirical evidence to suggest that high-intensity
interval exercise represents a greater risk to cardiac health
than low-intensity or moderate-intensity exercise.
Competing interests None.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.
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Table 2 LV volumes, mass and function
EDV
(ml)
ESV
(ml)
EF
(%)
Mass
(g)
Peak filling
rate (ml/s)
Study 1 (Nov 2008) 151 43 72 152 974
Study 2 (May 2011) 161 60 63 153 823
Study 3 (Mar 2012) 160 56 65 162 888
EDV, end-diastolic volume; EF, ejection fraction; ESV, end-systolic volume; LV, left
ventricular.
Godfrey R, et al. BMJ Case Rep 2013. doi:10.1136/bcr-2012-007668 3
Novel treatment (new drug/intervention; established drug/procedure in new situation)
21 Hermann TS, Dall CH, Christensen SB, et al. Effect of high intensity exercise on
peak oxygen uptake and endothelial function in long-term heart transplant
recipients. Am J Transplant 2011;11:53641.
22 Whyte G, Godfrey R, OHanlon R, et al. Acute myocardial infarction in the presence
of normal coronaries and the absence of risk factors in a young, life-long exerciser.
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25 Ellison GM, Torella D, Dellegrottaglie S, et al. Endogenous cardiac stem cell
activation by insulin-like growth factor-1/hepatocyte growth factor intracoronary
injection fosters survival and regeneration of the infarcted pig heart. J Am Coll
Cardiol 2011;58:97786.
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Novel treatment (new drug/intervention; established drug/procedure in new situation)
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