Download Can prolonged exercise-induced myocardial ischaemia be

Clinical research
European Heart Journal (2007) 28, 1559–1565
doi:10.1093/eurheartj/ehm152
Coronary heart disease
Can prolonged exercise-induced myocardial ischaemia
be innocuous?
Martin Noël, Jean Jobin, Audrey Marcoux, Paul Poirier, Gilles R. Dagenais, and Peter Bogaty*
Quebec Heart Institute, Laval Hospital, Laval University, 2725 Chemin Ste-Foy, Ste-Foy, Quebec, Canada G1V 4G5
Received 30 October 2006; revised 1 April 2007; accepted 6 April 2007; online publish-ahead-of-print 11 June 2007
See page 1543 for the editorial comment on this article (doi:10.1093/eurheartj/ehm187)
KEYWORDS
Ischaemia;
Exercise;
Coronary disease;
Electrocardiography;
Training
Aims To evaluate the innocuousness of intense and prolonged exercise training above the threshold for
myocardial ischaemia (1 mm ST-segment depression).
Methods and results Twenty-two patients with ischaemic heart disease (IHD) were randomized to exercise training either at a target intensity that induced myocardial ischaemia (ischaemic group) or that
adhered to current guidelines (control group). Training was progressively increased to 60 min under continuous electrocardiographic (ECG) monitoring. Cardiac troponin T (cTnT) was measured at various
intervals. Ambulatory ECG monitoring was performed before and after 6 weeks of training and left ventricular function was evaluated in the ischaemic group after at least 6 weeks of training. The ischaemic
group had myocardial ischaemia during the first 20, 40, and 60 min exercise sessions for 12.3 + 6.8,
29.0 + 12.9, and 49.8 + 2.2 min, respectively, with ST-segment depression ranging from 1.0 to
2.1 mm. No patient in either group demonstrated significant arrhythmias or increased cTnT. The ischaemic group had preserved left ventricular function.
Conclusion In patients with IHD, prolonged and repeated ischaemic training sessions up to 60 min can be
well tolerated without evidence of myocardial injury, significant arrhythmias, or left ventricular
dysfunction.
Introduction
It is generally accepted that exercise training intensity in
patients with ischaemic heart disease (IHD) should correspond to a heart rate that remains 10 b.p.m. below the
threshold for myocardial ischaemia (1 mm ST-segment
depression). This recommendation is enshrined in current
guidelines of exercise prescription1–4 and acknowledged in
textbooks of cardiology.5,6
A limitation of these guidelines is the restriction of
exercise training intensity, especially in patients who may
manifest myocardial ischaemia at a relatively low level of
exercise intensity. Such patients may be deprived of the
potential benefits of more intense exercise.7 Higher compared with lower exercise training intensity decreases
chronic heart disease risk factors,8 improves insulin sensitivity,9 increases cardiopulmonary fitness to a greater
degree,8,10 and imparts superior cardioprotective benefits.7
In a study over 25 years ago, high intensity exercise training in patients who developed exercise-induced myocardial
ischaemia was associated with increases in maximal
oxygen uptake (V̇O2peak) and myocardial oxygen consumption (MV̇O2).11 At about the same time, studies also
* Corresponding author. Tel: þ1 418 656 8711 ext. 5537; fax: þ1 418 656 4685.
E-mail address: [email protected]
suggested that exercise training could raise the heart rate
at which electrocardiographic (ECG) ischaemia occurred
and improve myocardial perfusion.12,13 Although these findings appeared promising in their implications for cardiopulmonary rehabilitation, myocardial ischaemia was not
monitored during this high-intensity exercise.
More recently, in a study of the warm-up angina phenomenon, we found that a first exercise was needed to induce
myocardial ischaemia of more than moderate intensity in
order to significantly attenuate myocardial ischaemia of a
second exercise that closely followed the first.14 Indeed,
exercise may also have a delayed attenuating effect on myocardial ischaemia in patients with stable angina.15 Thus,
previous studies provide an appropriate rationale to evaluate the potential benefit of prolonged and repeated
periods of exercise-induced myocardial ischaemia as part
of a training programme in subjects with coronary artery
disease.
However, safety had not been specifically addressed in
these older high intensity exercise-training studies.11–13
Before evaluating the physiological effects of a prolonged
more intensive exercise training protocol that would
induce myocardial ischaemia in patients with stable IHD,
the innocuousness of repeated ischaemic exercise needed
to be assessed in terms of myocardial injury, arrhythmia,
and effect on left ventricular function.
& The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: [email protected]
1560
Methods
Twenty-two patients with stable IHD documented by (i) a recent
(6 months) standard Bruce protocol treadmill test that was positive for myocardial ischaemia (1 mm horizontal or downsloping
ST-segment depression) and (ii) coronary angiography (70% arterial diameter narrowing of at least one major coronary artery)
and/or stress myocardial scintigraphic imaging (significant reversible perfusion defect) were recruited for this trial. Patients were
screened from summaries of outpatient cardiology visits and consecutive reports from the hospital exercise testing laboratory.
Patients were excluded if they had significant resting ECG abnormalities such as voltage criteria for left ventricular hypertrophy or
resting ST-segment depression .0.5 mm. The other main exclusion
criteria were recent acute coronary disease, significant arrhythmias, significant heart valve disease, heart failure, uncontrolled
hypertension, locomotion disability, and digoxin medication. The
hospital Ethics Review Board approved the study and an independent safety committee was mandated to monitor it. All patients
gave informed written consent.
Exercise testing
Before initiation of the study, the 35 potentially eligible patients
with a previous positive Bruce treadmill exercise test completed
an individualized ergocycle symptom-limited exercise test during
which V̇O2peak was evaluated as previously described.16 MV̇O2 was
estimated by the rate-pressure product (heart rate systolic
blood pressure) (RPP) at peak exercise. Oxygen pulse, a value
dependent on stroke volume and the difference between the arterial and mixed venous blood O2 content was calculated by dividing
V̇O2 by the simultaneously measured heart rate and was expressed
as mL O2/beat.17 One patient declined participation after initial
testing, 12 patients were excluded because either myocardial
ischaemia was absent on the ergocycle test (nine patients) or
occurred too close to the end of exercise (.90% of maximal workload; three patients). The latter two exclusion criteria were
deemed necessary to ensure that ischaemic exercise would be
feasible and tolerable. This exercise test was repeated after the
first three sessions of 60 min of continuous endurance exercise training that corresponded to 6 weeks of training.
Exercise programme
The 22 patients of the study exercised three times per week under
the continuous supervision of at least one of the two study exercise
specialists. The exercise sessions consisted of a brief warm-up
period of light intensity (5–10 min) followed by endurance exercise
(20–60 min) on a stationary ergocycle (Monark 878, Vansbro,
Sweden) under continuous ECG monitoring (discussed subsequently). After the endurance portion of the session, strength
training (15 min) of the major muscle groups was individually prescribed and followed by a cool-down phase (10 min) that included
flexibility exercises. Over a period of 6 weeks, the endurance exercise portion was progressively increased from 20 to 60 min and then
maintained for the remainder of the training programme, according
to each patient’s response and tolerance as per protocol design.
Endurance exercise portions of .40 min were separated by walks
of moderate intensity (5–10 min) in which patients were momentarily not monitored. This physically active pause favoured patients’
comfort that would have been compromised by too lengthy uninterrupted cycling activity. The total exercise sessions lasted between
50 and 95 min.
Patients were randomly divided into two groups that differed in
the intensity of the endurance exercise. The randomization
sequence was furnished by the research center statistician. The
control group exercised at an intensity that is currently recommended by the guidelines (10 b.p.m. below the heart rate at
which these patients had 1 mm ST-segment depression on the ergocycle exercise test).3 The ischaemic group trained at an intensity
M. Noël et al.
that induced at least 1 mm but no more than 3 mm of ST-segment
depression, provided that there were at most tolerable symptoms
of myocardial ischaemia (‘ischaemic zone’). In order to target and
remain within this ischaemic zone during endurance exercise, the
ECG was continuously monitored and recorded in all patients
during all exercise sessions using the MP 150 telemetry system
with the AcqKnowledge Software interface version 3.5.7 (Biopac
Systems, Santa Barbara, CA, USA). This monitoring system allowed
us to dynamically adjust exercise intensity in such a way that the
patients in the ischaemic group were constantly kept in their ischaemic zone, whereas patients in the control group were kept outside
it. The ECG lead that had shown the greatest ST-segment depression
on the ergocycle exercise test performed before initiation of the
study was used for continuous monitoring during the endurance
exercise portions. Blood pressure was manually measured using a
sphygmomanometer (Tycos 767, San Diego, CA, USA) half way and
at the end of each endurance exercise portion.
Marker of myocardial injury (troponin T)
Cardiac isoform troponin T (cTnT) was measured 18–24 h after the
first 20, 40, and 60 min of continuous endurance exercise which
corresponded to the first, 12th, and 21st sessions. cTnT was again
measured after the first 3 sessions that included 60 min of continuous endurance exercise. Measurements were performed in the
hospital clinical laboratory using the only available commercial
assay (Roche Inc., Mannheim, Germany). The decision limit for
myocardial injury was set at 0.1 mg/L.18
Arrhythmias and ST-segment depression
ECG telemetry was used to monitor for arrhythmias and to characterize the ST-segment depression pattern of the endurance exercise
portion of each training session. Figure 1 illustrates the endurance
exercise portion of one subject. Each dot represents a quantitative
ST-segment depression of one beat in time compared with the
average ST-segment measured just before the start of endurance
exercise while the patient was sitting on the ergocycle. A mean
regression line was calculated to determine the ischaemic time,
i.e. the amount of time in which the ST-segment depression was
1 mm, and the average ST-segment depression during that time.
The gap of missing data represents the active pause taken by the
patient in which the ECG was briefly not recorded.
Ambulatory electrocardiographic monitoring
In order to determine the incidence of daily arrhythmias that could
be related to an ischaemic training programme, ambulatory 24 h
ECG monitoring (Holter) was performed before initiation of the
study and following the first three sessions that included 60 min of
endurance exercise. The ambulatory recordings were acquired
Figure 1 Example of a computerized analysis of the ST-segment depression
(in mV) for an entire duration of a specific 60 min endurance exercise period
of one patient.
Innocuousness of prolonged excercise training
using a Marquette monitoring system (Marquette Electronics Inc.,
Milwaukee, WI, USA) and categorized into three periods: (i) 24 h,
(ii) daytime (8 a.m. to 6 p.m.), (iii) night-time (midnight to 6
a.m.). The recordings were divided into diurnal and nocturnal
periods because daytime activities often included exercising,
which may predispose to arrhythmias. An experienced technician
blinded to randomization edited the recordings. The analysis of
arrhythmias was computer-assisted (HRV Marquette Electronics
Inc.) and visually double-checked. Ectopic ventricular and supraventricular beats were classified as isolated premature contractions,
bigeminy, and salves. Premature ventricular contractions were subdivided into episodes of 10, 1–9, and 0 b.p.h. Ventricular salves
were also subdivided into episodes of 5 beats, 6–10 beats, .10
beats and characterized with corresponding heart rate.
Ventricular function
After at least 6 weeks of exercise training, all patients in the ischaemic group underwent transthoracic echocardiographic evaluation by
a cardiologist unaware of study details. Left ventricular systolic and
diastolic diameters were measured and left ventricular ejection
fraction was calculated.19
Statistical analysis
We estimated from our own and other previous work that a sample
size of 11 patients in the ischaemic exercise group and 11 patients in
the control group had 90% power (alpha error of 0.05) for detecting
a 20% increase in ischaemic threshold following an ischaemic training programme in the ischaemic group and assuming no change
in ischaemic threshold in the control group.11,14 We anticipated a
standard deviation (SD) of 20–25% for the ischaemic thresholds.11,14
Data are expressed as mean + SD unless otherwise stated. Comparisons of patient data between visits and between patient groups
were performed using two-way repeated ANOVA design with group
and time as fixed factors. Group-specific variances were investigated and all variables suggested a compound symmetry covariance
structure based on the likelihood ratios test as well as on Akaike’s
and Schwarz’s criteria. The Holter parameters were log transformed
to stabilize variances. The univariate normality assumptions were
verified with the Shapiro–Wilk test and multivariate normality was
verified with the Mardia test. The results were considered significant with P , 0.05. All analyses were performed with the statistical
package SAS, version 9.1.3 (SAS Institute Inc., Cary, NC, USA).
1561
Table 1 Clinical characteristics of the study subjects
Anthropometric data
Men
Age (years)
Weight (kg)
Body mass index (kg/m2)
Clinical history
Diabetes/impaired fasting
glucose
Arterial hypertension
Dyslipidaemia
Cardiac history
Previous myocardial
infarction
Left ventricular ejection
fraction (%)
Percutaneous coronary
intervention
Coronary bypass surgery
Drug therapy
Aspirin
Lipid-lowering agent
Beta-blocker
Nitrate
ACE-inhibitor
Calcium antagonist
Diuretic
Oral hypoglycaemic
Controls
(n ¼ 11)
Ischaemic
(n ¼ 11)
9
65 + 8
79.5 + 12.1
27.78 + 3.10
11
64 + 5
76.2 + 15.4
26.37 + 4.24
2 (18%)
4 (36%)
6 (55%)
11 (100%)
4 (36%)
9 (82%)
5 (45%)
6 (55%)
57 + 10
66 + 17
2 (18%)
5 (45%)
9 (82%)
5 (45%)
9 (82%)
10 (91%)
8 (73%)
5 (45%)
4 (36%)
1 (9%)
3 (27%)
1 (9%)
11 (100%)
11 (100%)
5 (45%)
4 (36%)
4 (36%)
3 (27%)
2 (18%)
3 (27%)
Mean + SD (%). ACE, angiotensin-converting-enzyme.
Twenty men and two women, aged 49–73, participated and
completed the study. The histories and clinical characteristics of the patients are summarized in Table 1. Most
patients had previously undergone surgical and/or percutaneous revascularization. Although half the patients had a
previous myocardial infarction, all of them had a left ventricular ejection fraction greater than 50%. Nine patients
experienced anginal symptoms on a regular basis (at least
once a week), whereas the others were generally asymptomatic on medical therapy. Patients were treated with standard medications that had neither been recently modified
before initiation of the study nor changed during the
study. Patients in each group were slightly overweight by
body mass index criteria.20 There were no significant imbalances in clinical characteristics in the ischaemic and control
groups.
training arm showed exercise-induced ECG myocardial
ischaemia and four patients regularly reported angina
during the training sessions. No session was discontinued
because of angina. For the ischaemic exercise group, the
mean times spent in the ischaemic zone during the first
20, 40 and 60 min of continuous endurance exercise which
also preceded cTnT measurements were 12.3 + 6.8,
29.0 + 12.9, and 49.8 + 2.2 min, respectively (Table 2).
Only one subject in the control group inadvertently
trained in the ischaemic zone (37 min of a 40 min period;
mean ST-segment depression: 1.2 mm) because of a scheduling error. By study design, the training workload for these
sessions was higher in the ischaemic group than in the
control group (Table 2). The estimated myocardial work
(as expressed by RPP) during the training session was also
higher in the ischaemic compared with the control group
for the first 20 min (17 354 + 6528 vs. 13 355 +
2936 b.p.m. mmHg,
respectively;
P ¼ 0.08),
40 min
(16 329 + 5407 vs. 12 452 + 2330 b.p.m. mmHg, respectively; P ¼ 0.04), and 60 min training sessions (18 750 + 5 698
vs. 13 352 + 2947 b.p.m. mmHg, respectively; P ¼ 0.02)
(Figure 2). This difference appeared to be driven by the
heart rate that was lower in the control group because systolic
blood pressure was comparable in both groups (Table 2).
Exercise training
Arrhythmias and ST-segment depression
The exercise training programme was well tolerated by all
patients. As per study protocol, all patients in the ischaemic
Mean ST-segment depression ranged from 1.0 to 2.1 mm
during the first 20, 40, and 60 min sessions in the ischaemic
Results
1562
M. Noël et al.
Table 2 Ischaemic (1.0 mm ST-segment depression) and exercise parameters of the exercise sessions preceding cardiac troponin T
measurements that corresponded to the first 20, 40, and 60 min of continuous exercise
Work load
(W)
20 min
Control
Ischaemic
40 min
Control
Ischaemic
60 min
Control
Ischaemic
Ischaemic time
(min)
ST-segment depression
(1.0 mm)
HR
(b.p.m.)
SBP
(mmHg)
57 + 13
76 + 32
P ¼ 0.012
0
12.3 + 6.8
0
1.1 + 1.2
89 + 9
96 + 22
P ¼ 0.043
155 + 27
160 + 40
P ¼ 0.7
53 + 25
93 + 33
P ¼ 0.015
0a
29.0 + 12.9
0
1.1 + 0.7
89 + 11
96 + 17
P ¼ 0.002
139 + 14
151 + 27
P ¼ 0.1
55 + 20
89 + 35
P ¼ 0.001
0
49.8 + 2.2
0
1.3 + 0.4
91 + 11
102 + 18
P ¼ 0.008
146 + 24
155 + 25
P ¼ 0.2
Values are mean + SD.
a
This excludes one subject who inadvertently trained in the ischaemic zone (37 min of a 40 min session; mean ST-segment depression: 1.2 mm) because of a
scheduling error.
Ambulatory electrocardiographic monitoring
Twenty-four-hour Holter monitoring analysis showed no
statistically significant difference in the occurrence of supraventricular (Table 3) and ventricular arrhythmias (Table 4)
before and after three sessions of 60 min of endurance training
were completed, which corresponded to 6 weeks of training.
Nor were there any significant differences when the data
were further examined in diurnal and nocturnal periods. One
four-beat ventricular salve at a rate of 92 b.p.m. occurred at
night following a non-exercising day in one patient in the
ischaemic group at the 6 weeks’ analysis.
Ventricular function
Following at least 6 weeks of training, all patients in the
ischaemic group had a resting left ventricular ejection fraction that was within normal limits (67 + 7%) and not significantly changed compared with the pre-exercise training
value (Table 1). Diastolic and systolic left ventricular dimensions remained within normal limits (51 + 5 and 29 + 5 mm,
respectively).
Exercise tests
Figure 2 Heart rate systolic blood pressure product (rate pressure
product) and myocardial ischaemia (ST-segment depression 1 mm) of subjects during the first 20, 40, and 60 min exercise period that preceded (by
18–24 h) the troponin T measurements.
group (Table 2). In the ischaemic group, tolerable angina
was experienced by one patient during the 20 min session,
by three patients in the 40 min, and by three patients in
the 60 min training session. Only occasional isolated premature ventricular contractions were observed during exercise
and to a similar degree in both groups.
Marker of myocardial injury (troponin T)
None of the patients in either group at any time had a positive elevation of cTnT. All measurements of cTnT remained
below the detection limit of the assay (,0.01 mg/L).
The ergocycle ECG test, performed after 6 weeks of training,
remained positive for myocardial ischaemia (1 mm
ST-segment depression) in all patients. The same nine patients
(36%) experienced angina during both exercise tests. The
maximal workload (watts) achieved increased in both groups
but maximum RPP did not increase (Table 5). There were no
significant differences in either group between V̇O2 and O2
pulse at baseline and at 6 weeks (Table 5).
Discussion
To our knowledge, this is the first reported study demonstrating that, in patients with stable IHD, prolonged and
repeated exercise, which induces myocardial ischaemia
under controlled conditions, is not deleterious and can be
well tolerated. Progressively introduced, repeated and prolonged ischaemic exercise was not associated with malignant or significant arrhythmias either while exercising or
during Holter monitoring, did not cause myocardial injury
Innocuousness of prolonged excercise training
1563
Table 3 Supraventricular arrhythmias during 24 h Holter monitoring
Control group
Premature contractions
Bigeminy
Salves
Ischaemic group
Baseline
6 weeks
Baseline
6 weeks
18 (4–45)
1 (0–3)
1 (0–3)
17 (4–71)
0 (0–2)
1 (0–3)
47 (30–82)
0 (0–1)
1 (0–2)
46 (29–122)
1 (0–2)
0 (0–2)
Data are expressed as median (inter-quartile range 25–75%).
Table 4 Ventricular arrhythmias during 24 h Holter monitoring
Control group
Premature contractions
Episodes 10 b.p.h.
Episodes 1–9 b.p.h.
Episodes 0 b.p.h.
Bigeminy
Salves
Ischaemic group
Baseline
6 weeks
Baseline
6 weeks
4 (1–17)
0
4 (1–11)
20 (12–23)
0
0
6 (3–19)
0
5 (3–10)
20 (12–23)
0
0
5 (1–35)
0
5 (1–7)
5 (1–7)
0
0
6 (2–60)
0
4 (2–14)
20 (6–22)
0
0a
Data are expressed as median (inter-quartile range 25–75%).
a
One four-beat ventricular salve at a rate of 92 b.p.m. occurred at night following a non-exercising day in one patient.
Table 5 Exercise test parameters at baseline and after 6 weeks of exercise training
Controls
Baseline
6 weeks
Ischaemic Group
Baseline
6 weeks
V̇O2 (mL O2/kg/min)
O2 pulse (mL/beat)
Workload (W)
Heart rate (b.p.m.)
RPP (b.p.m. mmHg)
19.1 + 5.1
19.6 + 5.1
12.8 + 4.6
12.9 + 4.2
127 + 49
138 + 50*
124 + 22
125 + 26
25 167 + 6 263
25 404 + 6 962
24.0 + 6.0
25.5 + 6.7
13.3 + 3.5
14.1 + 4.9
152 + 56
169 + 62*
138 + 22
137 + 20
27 308 + 7 495
27 123 + 7 872
Values are mean + SD. RPP, rate pressure product (heart rate systolic blood pressure).
*P , 0.05 between visits.
as evaluated by cTnT levels, and did not result in sustained
left ventricular systolic dysfunction or change in left ventricular systolic and diastolic dimensions.
The guidelines on exercise prescription in patients with
IHD recommend that training intensity should stay below
the threshold for myocardial ischaemia.1–6 To the best of
our knowledge, this important recommendation appears
essentially based on a single study performed over a
decade ago by Hoberg et al.,21 which suggested that ischaemic exercise confers an arrhythmic risk. In this latter study,
21 patients with coronary artery disease exercised on an
ergocycle for 10 min twice a week at 75% of maximal
heart rate for 12 months. Twenty-four-hour Holter monitoring was performed on the first day of training and repeated
on a training-free day. The authors identified 10 ischaemic
episodes that were associated with ventricular arrhythmias
in five patients. These arrhythmias consisted of increased
premature ventricular contractions, three ventricular
couplets, and one episode of non-sustained ventricular
flutter. The significance of these results is unclear given
the benign or uncertain prognostic nature of these
arrhythmias,22–24 the controversial relationship between
exercise-induced myocardial ischaemia and ventricular
arrhythmias,23,25 the absence of a baseline recording of
arrhythmic status, and the limited arrhythmic sampling
period. Importantly, the conclusions of this and previous
studies may not be applicable to ischaemic exercise experienced by the patients in our study because these previous
studies based their findings on maximal symptom-limited
exercise testing, whereas our patients were enrolled in a
structured and progressive training programme. Indeed, in
the study by Hoberg et al.,21 patients reached their prescribed training heart rate within 2 min, which corresponded
to 75% of maximal heart rate. They abruptly started and
ended a 10 min training session, whereas in our study,
patients began exercising with 5–10 min of warm-up
before starting endurance ischaemic exercise. Warm-up
exercise improves endurance performance26 and favours a
better adaptation to metabolic demand, particularly in
patients with coronary artery disease.27 Warm-up exercise
1564
also attenuates myocardial ischaemia14,28 and could well be
protective against deleterious arrhythmias.29 We performed
extensive baseline and training arrhythmic monitoring
representing 308 patient-hours that included 154 patienthours of ischaemic training compared with only 14 patienthours in the study by Hoberg et al.21 We found no differences in the occurrence of arrhythmias between the
control and ischaemic training groups and we observed no
malignant arrhythmias during near-continuous monitoring
during all training sessions in all subjects as well as during
24 h Holter monitoring. Our results suggest that progressive
exposure to repeated ischaemic exercise periods is not
pro-arrhythmic.
We measured serum cTnT to evaluate whether repetitive
exposure to exercise-induced myocardial ischaemia leads to
myocardial injury. Serum cTnT is considered sufficiently sensitive to detect even microscopic myocardial necrosis and
sufficiently specific so as not to be confounded by skeletal
muscle injury that can occur at higher exercise intensity.30,31 We found no evidence of myocardial injury in
these patients exposed to repeated bouts of ischaemic exercise. Serum cTnT was not only negative in all patients at all
times, but also remained consistently below the detection
limit (,0.01 mg/L) of the assay for all measurements.
Limitations
Although these findings are relatively robust and detailed,
they must be considered within the context of a carefully
selected and limited cohort of stable motivated patients
with preserved left ventricular dysfunction, training in a
controlled environment. Although we did not find sustained
left ventricular dysfunction with ischaemic exercise, we
cannot rule out transient ischaemia-induced left ventricular
dysfunction stunning32,33 because we did not study left ventricular function immediately after each ischaemic exercise.
However, this appears unlikely since V̇O2peak and O2 pulse,
both physiological variables closely related to cardiac function,34–36 were comparable between groups at all times and
did not decrease in the ischaemic group after 6 weeks of
ischaemic exercise. More study of ischaemic exercise is
needed to fully evaluate its physiological and possible cardioprotective effects compared with traditional training.
It would be premature to generalize these results to a
broader population of patients with IHD.
Conclusions
In controlled conditions, ischaemic exercise training does
not cause myocardial injury, does not appear arrhythmogenic, and does not result in sustained left ventricular dysfunction. This study encouragingly suggests that ischaemic
exercise training can be safely investigated in an appropriate environment to determine whether it may confer
greater cardioprotective and physiological benefits than
more standard less-intensive exercise programmes in
patients with coronary artery disease.
Acknowledgements
We gratefully acknowledge the support of the Quebec Heart Institute Foundation. We are indebted to Ms Luce Boyer for technical
support and to Dr Pierre Desgagné, Program Director of the Pavillion
M. Noël et al.
de Prévention de Maladies Cardiaques for providing training facilities. P.P. is a clinical-scientist supported by the Fonds de la
Recherche en Santé du Québe (FRSQ).
Conflict of interest: none declared.
References
1. Drews C. Guidelines for Cardiac Rehabilitation Programs. 2nd ed.
Champain, Illinoi: Humain Kinetics; 1995.
2. Gibbons RJ, Chatterjee K, Daley J, Douglas JS, Fihn SD, Gardin JM,
Grunwald MA, Levy D, Lytle BW, O’Rourke RA, Schafer WP, Williams SV,
Ritchie JL, Cheitlin MD, Eagle KA, Gardner TJ, Garson A Jr, Russell RO,
Ryan TJ, Smith SC Jr. ACC/AHA/ACP-ASIM guidelines for the management
of patients with chronic stable angina: a report of the American College
of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients With Chronic Stable
Angina). J Am Coll Cardiol 1999;33:2092–2197.
3. Franklin B. ACSM’s Ressource Manual for Guidelines for Exercise Testing
and Prescription. 3rd ed. Baltimore/Philadelphia/London: Williams &
Wilkins; 1998.
4. B Franklin. ACSM’s Guidelines for exercise testing prescription. 6th ed.
Philadelphia/Baltimore/New York: Lippincott Williams & Wilkins; 2000.
5. Braunwald B, Zipes D, Libby P. Heart Disease: A textbook of cardiovascular medicine. 7th ed. Philadelphia/London/Newyork W.B. Saunders;
2003.
6. Fuster V, Wayne A, O’Rourke RA. Hurst’s The Heart. 11th ed. New York/
St-Louis/San Francisco: McGraw-Hill Medical Publishing Division; 2004.
7. Swain DP, Franklin BA. Comparison of cardioprotective benefits of
vigorous versus moderate intensity aerobic exercise. Am J Cardiol
2006;97:141–147.
8. O’Donovan G, Owen A, Bird SR, Kearney EM, Nevill AM, Jones DW,
Woolf-May K. Changes in cardiorespiratory fitness and coronary heart
disease risk factors following 24 wk of moderate- or high-intensity exercise of equal energy cost. J Appl Physiol 2005;98:1619–1625.
9. DiPietro L, Dziura J, Yeckel CW, Neufer PD. Exercise and improved insulin
sensitivity in older women: evidence of the enduring benefits of higher
intensity training. J Appl Physiol 2006;100:142–149.
10. Duncan GE, Perri MG, Anton SD, Limacher MC, Martin AD, Lowenthal DT,
Arning E, Bottiglieri T, Stacpoole PW. Effects of exercise on emerging and
traditional cardiovascular risk factors. Prev Med 2004;39:894–902.
11. Ehsani AA, Heath GW, Hagberg JM, Sobel BE, Holloszy JO. Effects of 12
months of intense exercise training on ischemic ST-segment depression
in patients with coronary artery disease. Circulation 1981;64:1116–1124.
12. Froelicher V, Jensen D, Atwood JE, McKirnan MD, Gerber K, Slutsky R,
Battler A, Ashburn W, Ross J Jr. Cardiac rehabilitation: evidence for
improvement in myocardial perfusion and function. Arch Phys Med
Rehabil 1980;61:517–522.
13. Laslett LJ, Paumer L, Amsterdam EA. Increase in myocardial oxygen consumption indexes by exercise training at onset of ischemia in patients
with coronary artery disease. Circulation 1985;71:958–962.
14. Bogaty P, Poirier P, Boyer L, Jobin J, Dagenais GR. What induces the
warm-up ischemia/angina phenomenon: exercise or myocardial ischemia? Circulation 2003;107:1858–1863.
15. Crisafulli A, Melis F, Tocco F, Santoboni UM, Lai C, Angioy G, Lorrai L,
Pittau G, Concu A, Pagliaro P. Exercise-induced and nitroglycerin-induced
myocardial preconditioning improves hemodynamics in patients with
angina. Am J Physiol Heart Circ Physiol 2004;287:H235–H242.
16. Brassard P, Ferland A, Gaudreault V, Bonneville N, Jobin J, Poirier P. Elevated peak exercise systolic blood pressure is not associated with reduced
exercise capacity in subjects with Type 2 diabetes. J Appl Physiol 2006;
101:893–897.
17. Belardinelli R, Lacalaprice F, Carle F, Minnucci A, Cianci G, Perna G,
D’Eusanio G. Exercise-induced myocardial ischaemia detected by cardiopulmonary exercise testing. Eur Heart J 2003;24:1304–1313.
18. Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction
redefined–a consensus document of The Joint European Society of
Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000;36:959–969.
19. Dumesnil JG, Dion D, Yvorchuk K, Davies RA, Chan K. A new, simple and
accurate method for determining ejection fraction by Doppler echocardiography. Can J Cardiol 1995;11:1007–1014.
20. Obesity: preventing and managing the global epidemic. Report of a WHO
consultation. World Health Organ Tech Rep Ser 2000;894:1–253.
Innocuousness of prolonged excercise training
21. Hoberg E, Schuler G, Kunze B, Obermoser AL, Hauer K, Mautner HP,
Schlierf G, Kubler W. Silent myocardial ischemia as a potential link
between lack of premonitoring symptoms and increased risk of cardiac
arrest during physical stress. Am J Cardiol 1990;65:583–589.
22. Marieb MA, Beller GA, Gibson RS, Lerman BB, Kaul S. Clinical relevance of
exercise-induced ventricular arrhythmias in suspected coronary artery
disease. Am J Cardiol 1990;66:172–178.
23. Schweikert RA, Pashkow FJ, Snader CE, Marwick TH, Lauer MS. Association of exercise-induced ventricular ectopic activity with thallium myocardial perfusion and angiographic coronary artery disease in stable,
low-risk populations. Am J Cardiol 1999;83:530–534.
24. Partington S, Myers J, Cho S, Froelicher V, Chun S. Prevalence and prognostic value of exercise-induced ventricular arrhythmias. Am Heart J
2003;145:139–146.
25. Casella G, Pavesi PC, Sangiorgio P, Rubboli A, Bracchetti D.
Exercise-induced ventricular arrhythmias in patients with healed myocardial infarction. Int J Cardiol 1993;40:229–235.
26. Bishop D. Warm up II: performance changes following active warm up and
how to structure the warm up. Sports Med 2003;33:483–498.
27. Arai AE, Grauer SE, Anselone CG, Pantely GA, Bristow JD. Metabolic adaptation to a gradual reduction in myocardial blood flow. Circulation 1995;
92:244–252.
28. Bogaty P, Kingma JG Jr, Robitaille NM, Plante S, Simard S, Charbonneau L,
Dumesnil JG. Attenuation of myocardial ischemia with repeated exercise
in subjects with chronic stable angina: relation to myocardial contractility, intensity of exercise and the adenosine triphosphate-sensitive
potassium channel. J Am Coll Cardiol 1998;32:1665–1671.
Clinical vignette
1565
29. Tuomainen P, Hartikainen J, Vanninen E, Peuhkurinen K. Warm-up
phenomenon and cardiac autonomic control in patients with coronary
artery disease. Life Sci 2005;76:2147–2158.
30. Shave R, Dawson E, Whyte G, George K, Ball D, Collinson P, Gaze D. The
cardiospecificity of the third-generation cTnT assay after exerciseinduced muscle damage. Med Sci Sports Exerc 2002;34:651–654.
31. Akdemir I, Aksoy N, Aksoy M, Davutoglu V, Dinckal H. Does
exercise-induced severe ischaemia result in elevation of plasma
troponin-T level in patients with chronic coronary artery disease? Acta
Cardiol 2002;57:13–18.
32. Barnes E, Baker CS, Dutka DP, Rimoldi O, Rinaldi CA, Nihoyannopoulos P,
Camici PG, Hall RJ. Prolonged left ventricular dysfunction occurs in
patients with coronary artery disease after both dobutamine and exercise
induced myocardial ischaemia. Heart 2000;83:283–289.
33. Rinaldi CA, Masani ND, Linka AZ, Hall RJ. Effect of repetitive episodes of
exercise induced myocardial ischaemia on left ventricular function in
patients with chronic stable angina: evidence for cumulative stunning
or ischaemic preconditioning? Heart 1999;81:404–411.
34. Meyer TE, Karamanoglu M, Ehsani AA, Kovacs SJ. Left ventricular
chamber stiffness at rest as a determinant of exercise capacity in heart
failure subjects with decreased ejection fraction. J Appl Physiol 2004;
97:1667–1672.
35. Palmieri V, Palmieri EA, Arezzi E, Innelli P, Sabatella M, Ferrara LA,
Fazio S, Celentano A. Peak exercise oxygen uptake and left ventricular
systolic and diastolic function and arterial mechanics in healthy young
men. Eur J Appl Physiol 2004;91:664–668.
36. Weinberg R. Principles of Exercise Testing and Interpretation. 3rd ed.
Philadelphia/Baltimore/New York: Lippincott Williams & Wilkins; 1994.
doi:10.1093/eurheartj/ehl463
Online publish-ahead-of-print 5 February 2007
Unruptured congenital aneurisms of the right and left sinuses of Valsalva
Konstantinos Zannis1*, Boyan Tzvetkov1, Jean-François Deux2, and Ernest Wilhehelm Matthias Kirsch1
1
Department of Cardiothoracic Surgery, Henri Mondor Hospital, 51 avenue du Maréchal de Lattre de Tassigny, 94000
Creteil Cedex, France and 2Department of Medical Imaging, Henri Mondor Hospital, 51 avenue du Maréchal de Lattre de
Tassigny, 94000 Creteil Cedex, France
* Corresponding author. Tel: þ33149812172; fax: þ3349812152. E-mail address: [email protected]
Congenital unruptured aneurysms affecting both the right and
left sinuses of Valsalva are extremely uncommon. We report
the case of a 24-year-old African male admitted to our institution with a 1-year history of chest pain, palpitations, and
progressive exertional intolerance. During the past 10 days,
he had experienced an acute exacerbation of these symptoms.
The chest radiograph delineated an abnormal cardiothoracic
ratio. Electrocardiogram showed no ischaemic changes and a
first degree atrioventricular heart block associated with a
complete right bundle branch block and an incomplete left
bundle branch block. Transthoracic echocardiography showed
two large aneurysms of the left and the right coronary
sinuses of Valsalva. Transoesophageal echocardiography
(TOE) was performed showing extension of the right sinus of
Valsalva aneurysm into the interventricular septum and the
left sinus of Valsalva aneurysm appearing as an extracardiac
saccular protrusion (Panel A). A multi-slice computed tomography (CT) confirmed the diagnosis (Panel B). Considering
the large size of the right and the extracardiac extension of
the left coronary sinus aneurysms, operative repair was indicated. The operation was performed through median sternotomy under cardiopulmonary bypass (Panel C). Both aneurysms
were repaired through the ascending aorta by closing their orifices with circular Dacron patches. The native aortic valve was
preserved. Per-operative TOE confirmed complete aneurysm
exclusion without increase in the known aortic regurgitation
(Panel D). The patient was discharged from hospital on day 8
and is doing well 11 months after operation.
Panel A. TOE before surgical repair.
Panel B. Multi-slice CT-scan reconstruction.
Panel C. Intra-operative view of the aortic valve with the orifices of the right and left coronary sinus aneurysms.
Panel D. Post-operative TOE with left and right coronary sinuses aneurysms obstructed. LA, left atrium; RA, right atrium; LcsA, left
coronary aneurysm; RCsA, right coronary aneurysm, Ao, aorta; LV, left ventriculum, S, interventriculaire septum; RV, right ventriculum.