Disproportionate exercise load and remodeling of the athlete's right ventricle.

Abstract

There is evolving evidence that intense exercise may place a disproportionate load on the right ventricle (RV) when compared with the left ventricle (LV) of the heart. Using a novel method of estimating end-systolic wall stress (ES-σ), we compared the RV and LV during exercise and assessed whether this influenced chronic ventricular remodeling in athletes.
For this study, 39 endurance athletes (EA) and 14 nonathletes (NA) underwent resting cardiac magnetic resonance (CMR), maximal oxygen uptake (VO2), and exercise echocardiography studies. LV and RV end-systolic wall stress (ES-σ) were calculated using the Laplace relation (ES-σ = Pr/(2h)). Ventricular size and wall thickness were determined by CMR; invasive and Doppler echo estimates were used to measure systemic and pulmonary ventricular pressures, respectively; and stroke volume was quantified by Doppler echocardiography and used to calculate changes in ventricular geometry during exercise.
In EA, compared with NA, resting CMR measures showed greater RV than LV remodeling. The ratios RV ESV/LV ESV (1.40 ± 0.23 vs 1.26 ± 0.12, P = 0.007) and RV mass/LV mass (0.29 ± 0.04 vs 0.25 ± 0.03, P = 0.012) were greater in EA than in NA. RVES-σ was lower at rest than LVES-σ (143 ± 44 vs 252 ± 49 kdyn · cm, P < 0.001) but increased more with strenuous exercise (125% vs 14%, P < 0.001), resulting in similar peak exercise ES-σ (321 ± 106 vs 286 ± 77 kdyn · cm, P = 0.058). Peak exercise RVES-σ was greater in EA than in NA (340 ± 107 vs 266 ± 82 kdyn · cm, P = 0.028), whereas RVES-σ at matched absolute workloads did not differ (P = 0.79).
Exercise induces a relative increase in RVES-σ which exceeds LVES-σ. In athletes, greater RV enlargement and greater wall thickening may be a product of this disproportionate load excess.

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Disproportionate Exercise Load and
Remodeling of the Athlete’s Right Ventricle
ANDRE´LA GERCHE1,2, HEIN HEIDBU¨CHEL2, ANDREW T. BURNS3, DON J. MOONEY3, ANDREW J. TAYLOR4,
HEINZ B. PFLUGER4, WARRICK J. INDER1, ANDREW I. MACISAAC3, and DAVID L. PRIOR1,3
1Department of Medicine, St. Vincent’s Hospital, University of Melbourne, Melbourne, AUSTRALIA;2Cardiology Department,
University Hospital, University of Leuven, Leuven, BELGIUM;3Cardiology Department, St. Vincent’s Hospital Melbourne,
Melbourne, AUSTRALIA; and4Alfred Hospital and Baker IDI Heart and Diabetes Institute, Melbourne, AUSTRALIA
ABSTRACT
LA GERCHE, A., H. HEIDBU¨CHEL, A. T. BURNS, D. J. MOONEY, A. J. TAYLOR, H. B. PFLUGER, W. J. INDER, A. I.
MACISAAC, and D. L. PRIOR. Disproportionate Exercise Load and Remodeling of the Athlete’s Right Ventricle. Med. Sci. Sports
Exerc., Vol. 43, No. 6, pp. 974–981, 2011. Purpose: There is evolving evidence that intense exercise may place a disproportionate load
on the right ventricle (RV) when compared with the left ventricle (LV) of the heart. Using a novel method of estimating end-systolic
wall stress (ES-R), we compared the RV and LV during exercise and assessed whether this influenced chronic ventricular remodeling
in athletes. Methods: For this study, 39 endurance athletes (EA) and 14 nonathletes (NA) underwent resting cardiac magnetic reso-
nance (CMR), maximal oxygen uptake (V˙O2), and exercise echocardiography studies. LV and RV end-systolic wall stress (ES-R)
were calculated using the Laplace relation (ES-R = Pr/(2h)). Ventricular size and wall thickness were determined by CMR; invasive
and Doppler echo estimates were used to measure systemic and pulmonary ventricular pressures, respectively; and stroke volume was
quantified by Doppler echocardiography and used to calculate changes in ventricular geometry during exercise. Results: In
EA, compared with NA, resting CMR measures showed greater RV than LV remodeling. The ratios RV ESV/LV ESV (1.40 T 0.23 vs
1.26 T 0.12, P = 0.007) and RV mass/LV mass (0.29 T 0.04 vs 0.25 T 0.03, P = 0.012) were greater in EA than in NA. RVES-R was lower
at rest than LVES-R (143 T 44 vs 252 T 49 kdynIcmj2, P G 0.001) but increased more with strenuous exercise (125% vs 14%, P G 0.001),
resulting in similar peak exercise ES-R (321 T 106 vs 286 T 77 kdynIcmj2, P = 0.058). Peak exercise RVES-R was greater in EA than
in NA (340 T 107 vs 266 T 82 kdynIcmj2, P = 0.028), whereas RVES-R at matched absolute workloads did not differ (P = 0.79).
Conclusions: Exercise induces a relative increase in RVES-R which exceeds LVES-R. In athletes, greater RV enlargement and greater
wall thickening may be a product of this disproportionate load excess. Key Words: CARDIAC, WALL STRESS, RIGHT VENTRICLE,
ECHOCARDIOGRAPHY, MAGNETIC RESONANCE, LAPLACE
T
experimental data suggest that strenuous exercise may be
associated with accelerated RV dysfunction (14,21). How-
ever, exercise may also be an important determinant of RV
here has been recent interest in the role that exer-
cise plays in right ventricular (RV) remodeling. In
patients with pulmonary vascular and RV pathology,
function in healthy populations. In elite endurance athletes,
complex ventricular arrhythmias are commonly associated
with structural and functional abnormalities of the RV but
not the left ventricle (LV) (15). This syndrome occurs pri-
marily in those performing the highest volume of strenuous
exercise and is not explained by familial predisposition,
thereby suggesting that exercise may have a direct role in
RV remodeling (26). However, previous descriptions of
athletic cardiac remodeling, termed athlete’s heart, have
predominantly focused on the LV (27).
In a large nonathletic cohort, Aaron et al. (1) demon-
strated that RV mass and RV end-diastolic volumes in-
creased with the level of physical activity, independent of
LV measures. This is consistent with some animal studies
in which intense exercise resulted in a disproportionate in-
crease in RV mass when compared with the LV (2,3). In
endurance athletes, acute changes in RV structure and func-
tion are more prevalent and more profound than for the LV
when assessed immediately after intense prolonged exercise,
(24,30,31,40). In contrast, the few studies that have assessed
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Address for correspondence: Andre ´ La Gerche, M.B.B.S., Ph.D., Depart-
ment of Cardiology, St. Vincent’s Hospital, PO Box 2900, Fitzroy 3065,
Australia; E-mail: Andre.LaGerche@svhm.org.au.
Submitted for publication October 2010.
Accepted for publication November 2010.
Supplemental digital content is available for this article. Direct URL citations
appear in the printed text and are provided in the HTML and PDF versions of
this article on the journal’s Web site (www.acsmmsse.org).
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chronic RV structural remodeling in athletes have demon-
strated increases in volume and mass, which are proportional
to those of the LV (37,38).
The mechanism by which exercise may exert a dispro-
portionate effect on RV structure and function has not
been studied. During intense exercise, the relative pressure
increases in the pulmonary circulation exceed those of the
systemic circulation (4,8,22,25), and this, combined with a
simultaneous demand for greater output, provides a theoretical
basis by which greater RV stress may be appreciated. How-
ever, according to the principles of Laplace, wall stress may
be moderated by increases in wall thickness and/or reductions
in cavity size (41). The balance among pressure, ventricular
structure, and the resulting wall stress during exercise has
not been detailed for the RV.
We devised a minimally invasive method combining car-
diac magnetic resonance (CMR) imaging and echocardiog-
raphy to estimate end-systolic wall stress (ES-R) to examine
whether wall stress changes in the RV and LV during exer-
cise are different and whether a difference in RVES-R may
result in greater relative RV remodeling in athletes.
METHODS
Subjects. A total of 39 endurance-trained athletes (EA)
and 14 age- and sex-matched nonathletes (NA) volunteered
to participate in the study. EA were defined as subjects ac-
tively engaged in endurance sports competition, whereas
NA were defined as: 1) currently performing G3 h of mild
recreational exercise per week and 2) having no previous
involvement in regular sports competition. Any subject with
a risk factor for, or history of, cardiovascular disease was
excluded. Activity levels were assessed by questionnaire,
and subjects were asked to describe and quantify exercise
during a typical week within the preceding month. Training
and recreational exercise were defined as exercise performed
with and without intent for improvement in performance,
respectively.
EA were performing 16 T 5 hIwkj1of exercise train-
ing, and testing was performed in the 3–6 wk before one
of the following endurance sporting races: a marathon run
(7 athletes), a 207-km alpine cycling race (9 athletes), an
endurance triathlon (1.9-km swim, 90-km ride, and 21.1-km
run; 10 athletes), or an ultraendurance triathlon (3.8-km
swim, 180-km ride, and 42.2-km run; 13 athletes). The
athletes had been competing in endurance sport events for
10 T 9 yr (range = 1–45 yr). Well-trained amateur (90%) and
professional (10%) athletes were enrolled, and all athletes
completed the endurance event in a time less than the median
participant’s completion time. The recruited NA subjects all
performed some leisure time exercise activity (mean =1.7 T
0.4 hIwkj1) but no exercise for training effect. Written in-
formed consent was obtained, and the protocol was approved
by the St. Vincent’s Hospital ethics committee.
Cardiac morphology. CMR imaging was performed
on a 1.5-T scanner (Signa Excite; GE Healthcare, Waukesha,
WI) using a dedicated cardiac coil and electrocardiographic
gating. Cine imaging was used to obtain a contiguous short-
axis stack (slice thickness of 8 mm; no gaps) covering the
LV and RV from the apex to a level well above the atrio-
ventricular groove. Twenty images per cardiac cycle were
obtained at the end-tidal breath hold. Endocardial and epicar-
dial borders were manually traced using a standard system
software analysis tool (Cinetool; Global Applied Science
Laboratory, GE Healthcare) at end-diastole and end-systole to
quantify volume (EDV and ESV, respectively) by a summa-
tion of disks method (Fig. 1). Stroke volume (SVCMR) was
measured as the average of EDV minus ESV for both ven-
tricles. Myocardial mass was determined from myocardial
volumes (epicardial minus endocardial volume) after multipli-
cation by the specific density of myocardium (1.05 gIcmj3).
Papillary muscles were included in the ventricular mass and
excluded from volumes, and the interventricular septum
was treated as LV mass. All analyses were performed by
one observer blinded to subject identity (A.L.G.), with a
subset of seven randomly selected studies analyzed by a
second blinded observer (H.B.P.) for the assessment of in-
terobserver variability.
Exercise measures. Cardiopulmonary exercise test-
ing for V˙O2maxquantification was undertaken on an upright
cycle ergometer using an automated gas exchange measur-
ing system (ER900 and Oxycon Alpha, Jaeger, Germany).
Incremental exercise (12.5 WIminj1) was performed until
exhaustion.
Real-time echocardiography was performed separately
(between 2 and 7 d after cardiopulmonary exercise testing
on a semisupine cycle ergometer (Lode, Groningen, The
Netherlands) with the same exercise protocol.
Echocardiographic measures were obtained using a Vivid
7 Dimension echocardiograph (GE, Horten, Norway) and
stored for offline analysis (Echopac v.108; GE, Norway).
During exercise, pulmonary artery systolic pressure (PASP),
stroke volume (SVDopp), and RV fractional area change
(RVFAC) were obtained every 2 min. PASP was calculated
from maximal tricuspid regurgitant velocities with colloid–
contrast enhancement (agitated solution of succinylated gel-
atin (Gelofusine; Braun Intl., Melsungen, Germany) mixed
with room air (95:5 ratio)) using the modified Bernoulli
equation without the addition of a right atrial pressure esti-
mate, as has been validated against invasive measures at rest
and with exercise (17,20,23). SVDoppwas calculated from
the velocity–time integral from pulse wave Doppler inter-
rogation of the RV outflow tract, as previously described
(25). Using resting measures, SVDoppwas validated against
SVCMR. RVFAC was obtained from endocardial tracings of
specific echocardiographic views of the RV at end-diastole
(RVA-d) and end-systole (RVA-s) according to the follow-
ing formula: RVFAC = (RVA-d j RVA-s)/RVA-d.
Invasive blood pressure monitoring was performed
throughout exercise via a 22-gauge radial artery catheter
(Arrow Intl., Durham, NC) with continuous pressure trans-
duction monitoring (SpaceLabs, Inc., Redmond, WA). The
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monitor was carefully referenced such that zero pressure
was set with the transducer level with the subject’s mid-
axillary line. Dynamic response testing of the system was
performed to determine the natural frequency of the fluid-
filled circuit and ensure that the arterial pressure wave was
free of significant damping effects (12). The analog pressure
wave was recorded continuously while systolic and diastolic
values were recorded every minute during exercise.
Calculations. For the end-systolic wall stress (ES-R),
Laplace’s law was used to calculate R according to the
formula
ES ? R ¼ Pr=ð2hÞ
where P (pressure) was quantified as PASP and arterial
systolic blood pressure (SBP) for the RV and LV, respec-
tively; r (radius) was calculated from the ESV assuming
FIGURE 1—Multimodality method for end-systolic wall stress quantification. In the upper panels, CMR images of an athlete provide an example of
ventricular volume and mass analysis. SV was assessed throughout exercise using the velocity time integral of pulse wave Doppler flow at the level
of the pulmonary valve (lower left) with a strong correlation against resting CMR measures noting the significant bias from the line of equiva-
lence (lower middle). An example of pulmonary pressure estimates with contrast enhancement (lower right) with a tricuspid regurgitant velocity of
4.70 mIsj1(88 mm Hg) at peak exercise.
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spherical geometry, as previously described (28), by the
formula r = 0.620(ESV)1/3(for measures during exercise,
SVDoppwas subtracted from EDV, which was assumed to
remain constant throughout exercise); and h (wall thickness)
was calculated by subtracting r from the radius of the epi-
cardial volume, again assuming spherical geometry (thus,
because myocardial mass is preserved, h increases with
exercise-induced decreases in r).
Statistical analysis. Baseline and peak values were
compared using an independent t-test or W2for categorical
data. The effect of exercise was assessed using a mixed-
factorial ANOVA design, with exercise considered as a
within-subjects variable and EA versus NA and/or LV ver-
sus RV as between-subjects factors. Analysis of group effects
withrepeated exercise measureswas performed by comparing
mean slope coefficients from individual linear regressions.
Agreement of measures between tests and observers was
assessed according to the methods described by Bland and
Altman (7). The mean difference between measures, limits of
agreement, and Pearson correlation coefficient are quoted.
All values are expressed as mean T SD, and P G 0.05 was
considered significant. Statistical analysis was performed
using SPSS v.16.0 software (Chicago, IL).
RESULTS
Baseline characteristics. EA and NA participants
were well matched for age, gender, and height. Measures of
body habitus, exercise capacity, and cardiac morphology
were consistent with those expected for athletic trained and
untrained cohorts (Table 1). The body surface area of ath-
leteswas no different from NA (1.94 T 0.16 vs 1.94 T 0.14 m2,
P = 0.45) and had no influence on group comparisons.
Mean cardiac volumes were greater, and RV ejection frac-
tion (EF) was lower in athletes compared with NA (P G 0.001
for each measure), although LVEF was similar in both groups.
To address the hypothesis that athletic training may result in
disproportionate RV remodeling, the ratio of RV to LV mea-
sures was compared between groups. Figure 2 illustrates that
the difference between RV and LV volumes was greater in
EA relative to that in NA (with the exception of EDV), al-
though the difference in ventricular masses was relatively less.
There was good agreement between two observers for the
assessment of ventricular volumes. For the LV and RV, respec-
tively, therewasastrongcorrelationbetweenmeasures(r = 0.99
and r = 0.97, P G 0.001). As illustrated in the Bland–Altman
plots (Supplementary Figure 1,http://links.lww.com/MSS/A68),
minimal bias between observers was evident, with mean dif-
ferences of 3.9 T 14.3 and 9.5 T 20.4 mL. Agreement remained
acceptable for the determination of ventricular mass (mean
difference = 5.0 T 16.6 and 9.1 T 12.2 g), but values were less
well correlated, possibly reflecting the very small range of
values, particularly for RV mass (r = 0.77, P = 0.001 for LV
and r = 0.19, P = 0.53 for RV mass).
Changes in volumes, pressures, and wall stress
during exercise. To ensure the accurate assessment of
flow during exercise, resting SVDopp was compared with
SVCMR. A large bias, with consistently larger volumes by
CMR, was found (SVCMRj SVDopp= 50.37 T 16.7 mL, 95%
limits of agreement = 17.6–83.1 mL). The equation, SVCMR=
0.97SVDopp+ 52.7, was determined by linear regression, with
good correlation between measures (r = 0.72, P G 0.0001;
Fig. 1). Given the significant bias but otherwise good corre-
lation of values, this equation was subsequently used to cal-
culate SV from SVDoppduring exercise.
Baseline and peak exercise hemodynamic and cardiac
measures are shown in Table 2. CO increased to a greater
extent in athletes (P G 0.001) because of greater SV, which
was maintained through exercise. SV augmentation was due
to greater reductions in systolic volumes (as shown by the
TABLE 1. Baseline characteristics and CMR measures.
EA (n = 39) NA (n = 14)P
Age (yr)
Male (%)
Weekly exercise (h)
Height (cm)
Weight (kg)
V˙O2max(mL/kg/min)
No. predicted V˙O2max(%)
Max workload on V˙O2max(W)
Max workload on supine echo (W) 283 T 34
RV end-diastolic volume (mL)
LV end-diastolic volume (mL)
RV end-systolic volume (mL)
LV end-systolic volume (mL)
RV SV (mL)
LV SV (mL)
RVEF (%)
LVEF (%)
RV mass (g)
LV mass (g)
36 T 8
90
16.3 T 5.1
178 T 6
74 T 7
57.7 T 6.3
147 T 17
384 T 55
38 T 6
87
1.7 T 0.4
175 T 7
81 T 9
34.4 T 6.4
94 T 14
234 T 49
188 T 29
198 T 28
179 T 24
86 T 19
68 T 15
111 T 20
109 T 20
56.7 T 6.7
61.9 T 6.7
28.1 T 4.8
112.2 T 19.5
0.61
0.47
G0.0001
0.11
0.016
G0.0001
G0.0001
G0.0001
G0.0001
G0.0001
G0.0001
G0.0001
G0.0001
0.002
G0.0001
0.007
0.14
G0.0001
G0.0001
264 T 39
232 T 36
131 T 23
95 T 21
134 T 23
136 T 20
50.6 T 4.2
59.0 T 5.6
45.8 T 11.3
159.0 T 27.6
FIGURE 2—Relative differences in ventricular morphology. Endur-
ance athletes versus nonathletes. The RV/LV ratio is used as a measure
of relative ventricular remodeling. Greater ESV ratio, lower EF ratio,
and a trend toward a greater EDV in endurance athletes versus non-
athletes are demonstrated. In athletes, RV mass is also proportionately
greater than in NA.
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significant decrease in RVA-s), whereas end-diastolic di-
mensions were unchanged (RVA-d).
The variables used to calculate ES-R according to the La-
place relation ES-R = Pr/(2h) are detailed in Table 2. PASP
was able to be measured using contrast enhancement in all
subjects during exercise (median = 7 times, range = 2–11). It
increased to a greater extent with exercise than SBP (166% vs
36%, P G 0.001) and to a greater extent in EA than in NA
(182% vs 118%, P G 0.001). At rest and at peak exercise, r
was greater in the RV than in the LV (P G 0.0001), and lastly,
exercise-induced increases in h were significantly greater in
the LV than in the RV (P G 0.001). Thus, each measure
changed in a manner that would augment ES-R more in the
RV than in the LV during exercise. Figure 3 illustrates the
exercise-induced changes that were greater in RVES-R rela-
tive to LVES-R (125.2% vs 13.6%, P G 0.001) and were
greater in EA than NA for RVES-R but not LVES-R.
The relationship between exercise intensity and RVES-R
response in EA versus NA during strenuous exercise is de-
tailed in Figure 4. The mean regression line for EA (derived
as the mean of each subject’s individual regression) is rep-
resented by the equation RVES-R = 0.739 ? watts + 145
which was not significantly different from that for NA,
RVES-R = 0.776 ? watts + 144, P = 0.78 and P = 0.94
for variables and constants, respectively. These regressions
were obtained from strongly correlated data, with a mean
correlation coefficient of r = 0.85 and r = 0.81 for athletes
and NA, respectively. Therefore, the increase in RVES-R
is similar between EA and NA at equivalent absolute exer-
cise intensity, but the peak exercise values differ because
of a greater maximal workload in the EA group.
DISCUSSION
In assessing biventricular ES-R, we provide a comprehen-
sive estimate of left and right ventricular afterloads during
strenuous exercise in healthy subjects (32). This provides a
novel insight into the differential stress imposed by exercise
on the RV and LV and helps explain why prolonged intense
exercise results in cardiac fatigue, which disproportionately
affects the RV (24,30,31,40). Our data confirm previous find-
ings that, in healthy subjects, strenuous exercise can result in
considerable increases in pulmonary artery pressures (4,6,8).
However, previous studies have not directly compared simul-
taneous measures of pulmonary and systemic arterial pres-
sures. In addition, they have not assessed whether pressure
excesses are counterbalanced by increases in wall thickness or
reductions in cavity radius sufficient to moderate increases
in wall stress. In considering all of these factors, we demon-
strate that exercise-induced increases in RVES-R are relatively
greater than those in LVES-R. We also demonstrate that in-
creases in RVES-R are proportional to exercise intensity and
that those who perform more frequent strenuous exercise
(athletes) have greater structural RV changes relative to the
LV when compared with those doing no training (NA). Thus,
there is consistency between the acute hemodynamic stressors
during exercise and the chronic structural changes of the heart,
both of which affect the RV to a greater extent than the LV.
Direct quantification of ES-R is impossible, and so esti-
mation is reliant on computational models, all of which share
common principles, namely, that ES-R increases with in-
creasing pressure and cavity radius while being offset by
greater wall thickness (18,19,29,41). Most ES-R studies have
focused on the LV and have suggested that differing com-
putational frameworks create modest differences in values but
that their relative changes in various pathological states are
appropriate (41). Furthermore, the use of simple models, such
as the thin-walled sphere approximation of Laplace, may be
as reliable as more complex formulas are (18). Quaife et al.
(35) used the Laplace relation and CMR measures to measure
RVES-R in pulmonary hypertension in the only other study
assessing RVES-R in humans of which we are aware. They
demonstrated that CMR measures of the RV cavity and wall
volumesweresufficientlyaccuratetoenablesuchquantification,
an assertion that is supported by the low interobserver vari-
ability reported here and previously (13), and used RVES-R to
TABLE 2. Baseline and peak exercise determinants of cardiac output and wall stress comparing EA versus NA.
BaselineEA vs NA
P
Peak ExerciseEA vs NA
P
Interactiona
PNA EANAEA
HR (beats per minute)
SV (mL)
CO (LIminj1)
RVA-d (cm2)
RVA-s (cm2)
RVFAC
End-systolic wall stress components
PASP (mm Hg)
SBP (mm Hg)
RVES (mL)
r-RVES (mm)
LVES (mL)
r-LVES (mm)
h-RVES (mm)
h-LVES (mm)
71 T 10
110 T 14
7.8 T 1.6
20.2 T 4.3
9.7 T 2.5
0.52 T 0.08
59 T 9
139 T 13
8.3 T 1.3
26.7 T 4.2
12.8 T 2.2
0.52 T 0.06
G0.001
G0.001
0.289
G0.001
G0.001
0.797
144 T 18*
130 T 17*
18.7 T 4.0*
20.0 T 4.6
8.3 T 2.9
0.58 T 0.11
149 T 14*
156 T 19*
23.0 T 3.3*
26.2 T 4.5
9.5 T 2.8*
0.64 T 0.08*
0.316
G0.001
G0.001
G0.001
0.218
0.046
0.002
0.515
G0.001
0.815
0.030
0.025
21.6 T 3.8
133.0 T 11.6
87.7 T 24.0
27.3 T 2.8
68.7 T 17.9
25.2 T 2.4
2.65 T 0.52
9.46 T 1.21
21.7 T 3.8
148.2 T 14.5
125.8 T 30.7
30.8 T 2.7
92.1 T 27.8
27.7 T 2.8
3.36 T 0.75
10.91 T 1.40
0.983
0.001
G0.001
G0.001
0.006
0.006
0.003
0.002
47.0 T 6.5*
182.5 T 22.3*
67.3 T 23.4*
24.9 T 3.1*
48.3 T 17.3*
22.2 T 2.9*
3.15 T 0.84*
11.03 T 2.03*
61.1 T 12.7*
200.3 T 25.0*
108.4 T 33.9*
29.2 T 3.5*
74.7 T 29.7*
25.6 T 3.9*
3.74 T 1.07*
12.09 T 2.16*
G0.001
0.019
G0.001
G0.001
G0.001
0.006
0.075
0.124
G0.001
0.667
0.524
0.157
0.524
0.244
0.511
0.372
*P G 0.001 for peak exercise versus baseline.
aInteraction between exercise and athletic status on mixed-factorial ANOVA analysis.
CO, cardiac output; h-RVES/h-LVES, end-systolic myocardial thickness of the RV and LV; r-RVES/r-LVES, end-systolic radius; RVA-d and RVA-s, right ventricular area at end-diastole
and end-systole; RVFAC, RV fractional area change.
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scrutinize the complex balance between RV load and remod-
eling. Our finding that the pronounced increases in RVES-R
during strenuous exercise may provide an additional stimu-
lus for ventricular remodeling supports their observations.
Studies of ES-R response to exercise have been confined
to the LV and have produced inconsistent results that may be
attributed, at least in part, to the substantive differences in
methods (9,10,16). Our use of shared measures and assump-
tions to compare ES-R in the RV and LV may be expected to
result in some canceling of potential systematic errors. We
demonstrate that relative exercise-induced increases in PASP
were considerably greater than those in SBP. Confidence may
be placed in these findings given that invasive SBP measures
are more reliable than sphygmomanometer recordings during
exercise (33), and the contrast-enhanced Doppler technique
used for PASP estimates has been shown to correlate well
with invasive measures at rest and during exercise (17,20,23).
Although the magnitude of difference is less pronounced,
we also found that peak exercise volumes, and hence ven-
tricular radii, were greater in the RV and that wall thickening
was relatively less. Combined, this creates a compelling basis
for our finding that exercise-induced increases in ES-R are
greater for the RV than LV.
In the first study to highlight differences in RV load to
exercise, Bossone et al. (8) found that athletes had greater
exercise-induced increases in PASP than in NA at equivalent
workloads. Such a finding implies a different, and seemingly
disadvantageous, pulmonary vascular response to exercise in
athletes. In contrast, we describe a linear dose–response rela-
tionship between RVES-R and exercise intensity, which does
not differ according to athletic training (Fig. 4). Rather, peak
RVES-R is determined by the absolute intensity of exercise—
the greater the exercise load, the greater the afterload.
We also contend that the current description of athletes’
heart may be incomplete. We found that the RV/LV volume
ratio at end-systole was greater and the ratio for EF was lower
in EA compared with that in NA. This is consistent with our
hypothesis that greater RV loading may be matched by greater
RV remodeling. Although there are a number of studies using
FIGURE 3—Changes in end-systolic wall stress with maximal exercise.
In the whole cohort, RVES-R was lower at rest but increased to a
greater extent such that it approximated LVES-R at peak exercise (A).
LV ES-R increases with exercise were modest and did not differ be-
tween EA and NA (B), whereas exercise resulted in a greater RVES-R
in EA versus NA (C). *P value for the interaction between exer-
cise (within-subject factor) and subgroup (EA vs NA or RV vs LV as
between-subject factors) on mixed-factorial ANOVA. Baseline and
peak exercise P values are obtained from independent-samples t-tests.
Error bars, SD.
FIGURE 4—RVES-R in athletes and nonathletes at matched work-
loads. Multiple RVES-R measures at different exercise intensities en-
abled individual linear regressions to be calculated. The means of these
individual regressions were almost identical for athletes (blue dotted line
defined as RVES-R = 0.052 ? watts + 10.95) compared with nonathletes
(red line, RVES-R = 0.053 ? watts + 10.60), P = 0.94 for comparison.
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CMR to describe cardiac morphology in athletes, few have
provided a comprehensive description of the RV. Scharhag
et al. (38) described symmetrical ventricular enlargement in
21 endurance athletes who were considerably younger than
our cohort (27 T 5 vs 36 T 8 yr), and this may suggest that the
athletes had been involved in competitive sport for a shorter
period. Cumulative exposure to the hemodynamic stressors of
intense exercise may be an important determinant of structural
remodeling, although this hypothesis has not previously been
explored. Other investigators used CMR measures to demon-
strate chronic RV enlargement (34) or acute RV dilation after
prolonged exercise (30,40), which was greater than for the LV.
It is difficult to draw firm conclusions from these disparate
results especially when one considers that the degree of ven-
tricular asymmetry resulting from exercise is likely to be
slight, if present at all. It could be argued that all previous
studies in athletic cohorts have been underpowered to assess
subtle ventricular differences. This proposition is supported
by the results of Aaron et al. (1), who recruited a large cohort
of 1867 NA to demonstrate that the amount of strenuous ac-
tivity predicted RV mass and volumes independent of LV
size. Our finding of greater relative RV structural changes in a
middle-aged cohort of athletes with an extensive history of
competitive sport challenges the notion that athletes develop
balanced ventricular hypertrophy, although, once again, the
cohort is too small to definitively change conceptions.
Limitations. Several assumptions are required in our
approximation of wall stress and its relation to chronic car-
diac remodeling. The effect of these assumptions on the
overall study conclusion is reduced by the fact that they
apply equally to both ventricles and are therefore diminished
when considering relative changes. The Laplace equation
was used given that it is the simplest construct by which
wall stress may be considered, and a more accurate model
of load estimates remains elusive. Although our assumption
of spherical geometry to determine radii of curvature may be
an oversimplification, especially for the complex shape of
the RV, Arts et al. (5) have suggested that ES-R remains
related to cavity and wall volumes independent of geometry.
The use of Doppler-derived SV during exercise required
adjustment for significant bias to enable integration with
CMR measures. We feel that the improved accuracy of
CMR measures outweighs the error introduced through this
correction. Also, it was necessary to assume that EDV
remained constant through exercise, but numerous imaging
studies have demonstrated that this reflects reality, as de-
tailed in a review by Rowland (36). This assertion is further
supported by our finding that RV end-diastolic area (an
RVEDV surrogate) was unchanged throughout exercise.
It is notable that invasive measures of systemic blood
pressures were elevated at baseline, particularly in the ath-
letes. This may suggest underlying hypertension and latent
LV disease. However, no subject had a history of clinical
hypertension, and normal blood pressures were measured
by a sphygmomanometer immediately before the insertion
of the arterial lines. Also, the ‘‘peak exercise’’ HR and CO
were lower than may be expected during maximal upright
exercise. This may be explained by the recording of peak
values at the maximal intensity at which PASP and SV could
be reliably measured. This occurred close to maximal exer-
cise, with no difference between EA and NA groups. The
semisupine exercise also contributed to lower maximal HR
than would be expected with upright exercise.
Although EA and NA were well matched for age, sex,
and body surface area, NA were heavier, and this may have
influenced comparisons in ventricular remodeling. Finally,
our assertion that acute exercise hemodynamic stressors ex-
plain disproportionate RV enlargement and hypertrophy is
based on estimates of end-systolic wall stress although end-
diastolic wall stress (a measure of preload) is possibly a more
directstimulusforventricularenlargement.Wewereunableto
directly estimate end-diastolic pulmonary pressures using
echocardiographic techniques during exercise. However, in-
vasive measures suggest that systolic and diastolic pulmonary
pressures are linearly related and remain so during exercise
(39). Therefore, a similar imbalance in relative increases in
RV versus LV preload may also be expected, although this
remains to be established.
Clinical relevance. We have demonstrated that exercise-
induced increases in RVES-R are considerably greater than
those of LVES-R and that athletes have relatively greater RV
ESV than LV ESV and lower RVEF than LVEF. This has
direct application to sports cardiology practice where the
distinction between athletes’ heart and RV pathology can be
difficult (27). Our results suggest that reduced RVEF and
relative RV enlargement are expected in athletes and should
not necessarily be interpreted as a sign of pathology. Further
work is required to define the diagnostic cutoff between
the measures of RV function in our healthy athletes com-
pared with the low RVEF described by Ector et al. (11) in the
context of athletes with complex ventricular tachyarrhyth-
mias. Perhaps RV evaluation during exercise (when load is
greatest) may prove to be the best discriminator.
This project was financed, in part, by a Cardiovascular Lipid Grant
(Pfizer, Australia). A. L. G. is supported by a postgraduate scholar-
ship (National Health and Medical Research Council/National Heart
Foundation, Australia). A. J. T. is supported by a National Health and
Medical Research Council Program Grant, Australia.
All authors had full access to and take full responsibility for the
integrity of the data. The authors agree to the article as written. None
of the authors have professional relationships with any companies or
manufacturers who will benefit from the results of the present study.
The results of the present study do not constitute endorsement
by the American College of Sports Medicine.
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