CURRICULUM IN CARDIOLOGY
The prognostic value of exercise
review of the literature
Charles K. Morris, MD, Kenji Ueshima, MD, Takeo Kawaguchi, MD,
Alisa Hideg, and Victor F. Froelicher, MD. Long Beach, Calif.
Defining noninvasive parameters that are predictive
of cardiovascular mortality has long been a goal of
researchers and clinicians alike. Since Ellestad and
Wan’s pioneering work in 1975l up to the present,
there has been a plethora of prospective and retro-
spective studies endeavoring to sort out the “wheat
from the chaff” in exercise testing parameters. Exer-
cise capacity, as estimated by exercise duration or
work load during an exercise test, has been thought
by clinicians to be a significant predictor of cardio-
vascular mortality. This review discussesthe signif-
icant research in this field and attempts to define the
relevance of exercise capacity.
Exercise work load has been well correlated with
maximal ventilatory oxygen uptake (VOa max) for
the various treadmill and bicycle protocols within a
known margin of error. But over the years, debate has
continued as to the validity of estimation versus
measurement using expired gas analysis of VOa max.
Using a single exercise test as a measure of a patient’s
exercise capacity has also been controversial. Most
authorities will readily admit the shortcomings of the
exercise test, yet it has nonetheless become recog-
nized not only as the most convenient form of assess-
ment, but as the most quantitative and reproducible
as well. While it may not indicate overall physical
fitness, it does correlate with maximal aerobic capac-
ity, which relates well to maximal cardiac output.
The aerobic cost or VOz max (in ml Op/kg/min) of
treadmill exercise can be calculated by means of the
following formula2: VOZ max = (mph x 26.8) x
(0.1 + [ % grade x 1.81) t 3.5. This assumesthat the
individual is not being carried along by the handrails
or relying on anaerobic metabolism.3 Since a person’s
From the Cardiology Section, Long Beach Veterans Administration Med-
ical Center.
Received for publication March 20, 1991; accepted May 9, 1991.
Reprint requests: Charles K. Morris, MD, Cardiology Section (lllc), Long
Beach VA Medical Center, 5901 East Seventh St., Long Beach CA 90822.
4/l/32462
capacity: A
basal oxygen requirement to maintain life in the
resting state is approximately 3.5 ml O&g/min, this
has been designated as 1 MET (metabolic equiva-
lent), and multiples thereof have been used to de-
scribe levels of VO2 max (i.e., 35 ml OJkg/min = 10
METs).~ As most treadmill protocols proceed in spe-
cific timed steps (mph/% grade), exercise time re-
lates to oxygen consumption (METS), although the
accuracy of this relationship has been questioned.5
The advantage of reporting results in terms of METS
rather than in minutes is that different protocols can
thereby be more meaningfully compared and exercise
test performance can be related to everyday activi-
ties.
The questions that we shall discussthat have been
addressed by the various studies include: (1) Is exer-
cise capacity an independent predictor of cardiovas-
cular mortality? (2) Is exercise capacity an indepen-
dent predictor of all causes of death? (3) Are there
particular MET levels that can predict differences in
survival?
CARDIOVASCULAR MORTALITY
We excluded from our analysis studies of exercise
capacity involving patients who had suffered recent
myocardial infarctions. The reasons for this were the
frequency of submaximal treadmill tests in such
studies, which may not give an accurate assessment
of true exercise capacity, and the high mortality rate
already inherent in this group. Certainly this sub-
group has already been addressed in the literature. In
a me&analysis of the prognostic value of exercise
testing in patients after a recent myocardial infarc-
tion, Froelicher et al6 found that 12 of 14 studies that
considered exercise capacity showed an increased
risk for those patients with a poor exercise capacity.
Also excluded from review were four studies of
asymptomatic populations that used exercise testing
as a measure of exercise capacity and examined its
relationship to cardiovascular mortality. These stud-
ies (i.e., Lipid Research Clinics [LRC], Multiple Risk
1423

1424 Morris et al.
Factor Intervention Trial [MRFIT], LA County
Workers, and Aerobic Research in Dallas7-‘O) all
found a positive correlation between poor exercise
capacity and cardiovascular mortality.
Of the studies we reviewed, 12 addressed the issue
of whether exercise capacity was a predictor of car-
diovascular death. Ellestad and Wan’ conducted a
retrospective study of 2700 patients referred for a
variety of reasons to their treadmill laboratory who
were then followed from 6 months to 9 years (no mean
follow-up given) for subsequent cardiac morbidity or
mortality. The main focus of this study was on the
predictive capacity of ST segment changes. Their
main finding was that an early onset of ischemic
electrocardiographic changes predicted a higher mor-
tality rate and number of cardiac events. They indi-
rectly assessed exercise capacity, finding that “chro-
notropic incompetence” (the pulse rate is below the
95% confidence interval for a given work load, age,
and sex) forecasted a significant increase in myocar-
dial infarctions, the progression of angina, and deaths.
McKirnan et al.‘l have reported subsequently that
maximal heart rate is the main determinant of
treadmill work load achieved; thus chronotropic in-
competence may be inferred to reflect a reduction in
exercise capacity. This increased risk was equivalent
to that found in patients who had positive ST
segments. It should be noted that while this study
used a chi square analysis, no multivariate or survival
analysis techniques were used.
Bruce et a1.l’ in 1977 published a prospective study
of 1852 men from the Seattle Heart Watch Study who
had a clinical history of coronary artery disease.
These men were then followed during medical treat-
ment for an average of 3 years. They found conclu-
sively that a poor exercise capacity (as measured by
a low duration of exercise) predicted a higher inci-
dence of sudden cardiac death. This was valid using
both univariate and multivariate analysis of clinical
and exercise data. In a subsequent study published in
1983,13 they prospectively followed 3611 men and 547
women, free of clinically evident coronary artery dis-
ease at enrollment, for a total of 10 years. In a sub-
category of asymptomatic men without atypical chest
pain or hypertension, they discovered that any single
clinical risk factor (age >55, hypertension, any his-
tory of tobacco use, male gender) when combined
with two or more exercise variables (angina, heart
rate <90% predicted, double product <80% pre-
dicted, functional aerobic impairment >20%, func-
tional age >55 years) predicted a thirty-threefold in-
crease in cardiac events (worsened angina, myocar-
dial infarction, coronary artery bypass surgery,
death). Functional aerobic impairment is a term de-
November 199 1
Ametkan Heart Journal
fined by Bruce’* in 1971 as “the difference between
observed VOz max and that expected for a healthy
person of similar age, sex and habitual activity
status.”
Hammermeister et al.‘” in 1979 analyzed retro-
spectively a separate group from the Seattle Heart
Watch Study made up of 2603 patients who were
separated into two nonrandomized groups, coronary
artery bypass surgery versus medical treatment. Fol-
low-up averaged 3.6 years. Only 46% of these pa-
tients underwent treadmill testing. Multivariate
analysis of the exercise test variables alone found a
low double product and a low treadmill time to be
predictive of increased mortality. But when the
exercise variables were considered multivariately
with both the clinical and angiographic variables, no
exercise variables were found to be independently
predictive of mortality. It should be noted, however,
that they excluded treadmill variables from their fi-
nal multivariate analysis because of the low percent-
age of patients having undergone treadmill testing,
and this certainly weakens any conclusions made
from this analysis.
McNeer et all6 published a retrospective study in
1979 of 1472 patients who had significant coronary
disease by angiography, an exercise test, and received
either medical or surgical therapy (nonrandomized).
Multivariate analysis of the medically treated pa-
tients showed an abnormal ST segment response and
a low exercise stage to be significant independent
predictors of mortality after 4 years of follow-up. Of
great interest was their finding that patients who had
a normal ST segment response and achieved stage IV
of a Bruce protocol (13 METS) or higher had a near
100% 4-year survival. Patients with a positive ST
segment response who only achieved stage I of a
Bruce protocol (5 METS) or less had a high preva-
lence of triple-vessel/left main disease (73% and
27 % , respectively) and had a very poor prognosis (4-
year survival rate less than 60 % ).
Platia et al.” retrospectively studied 78 patients
who received coronary angiograms between 1960 and
1967 and had a greater than 70% stenosis of at least
one coronary artery and were “suitable for surgery”
by 1978 standards but received medical therapy at
the time. Sixty-eight of these patients performed a
Master double two-step test that was halted for
symptoms or the attainment of the predicted number
of steps. Follow-up was a mean of 9.9 years. Multi-
variate analysis of clinical, exercise, and angiographic
variables did not find exercise test time to be predic-
tive of survival. It should be noted, however, that this
was a small study using the step test, which did not
permit estimation of exercise capacity.
Volume 122
Number 5 Prognostic
Podrid et all8 published a prospective study in
1981 on 14‘2 male patients with coronary artery dis-
ease by history or by cardiac catheterization who had
>2 mm ST segment depression on at least two suc-
cessive Bruce protocol treadmill tests. These patients
received medical management and were followed an
average of 59 months. The patients were divided into
three categories during follow-up: group 1 were those
who exercised 1 to 6 minutes (average 4.2 minutes, 6
METS); group 2 exercised 6 to 9 minutes (average 7.5
minutes, 8 METS); and group 3 exercised >9 minutes
(average 10.2 minutes, 11 METS). There was a
significant decrease in survival in group 1 compared
with both groups 2 and 3. No difference in survival
existed between groups 2 and 3 themselves.
In a prospective study of 147 men and women at
the National Institute of Health published in 1982,
Kent et al.lg looked at the predictive capacity of ex-
ercise testing for short-term mortality (1 year) in pa-
tients with known coronary artery disease by angiog-
raphy (>50% stenosis of a major coronary artery).
This group of patients had only mild or nonexistent
angina, were younger than 65, did not have signifi-
cant left main stenosis, and had a left ventricular
ejection fraction >20 % . They all received medical
therapy and were followed an average of 2 years
(range 6 to 67 months). Exercise capacity was not
found to predict short-term mortality, except in the
subgroup of patients with triple-vessel disease. In
this subgroup, an exercise capacity of <lOO W (2
METS) on an upright bicycle ergometer doubled the
mortality rate of those able to go more than 100 W.
This difference became statistically significant at 1
year.
Sawada et aL2’ prospectively followed 170 pa-
tients with normal resting and exercise echocardio-
grams. These patients were followed medically for
an average of 28.4 months until they died or had a
cardiac event (percutaneous transluminal coronary
angioplasty, coronary artery bypass surgery, or
myocardial infarction). Follow-up was 87% com-
plete. Their results, published in 1990, were that
cardiac events were far more frequent in those pa-
tients who achieved <6 METS (8.9% versus 1.1% )
or <85% maximal predicted heart rate (10.9 %
versus 1.0%). In addition, they concluded that a
patient with a normal exercise echocardiogram and
a good exercise capacity has an excellent short-term
prognosis, even if he exhibits exercise-induced
ST segment depression.
A great deal of work has been done in this area by
Weiner et al. with groups of patients from the Coro-
nary Artery Surgery Study (CASS) registry. In 1984
theyzl published a retrospective study of 4083 pa-
value of exercise capacity 1425
tients with no prior coronary artery bypass surgery or
recent myocardial infarction who underwent coro-
nary angiography, left ventriculography, and exercise
testing within 1 month of each other. Follow-up was
a minimum of 3 years (average follow-up not stated),
alJ it was 99% complete. The 1474 patients who un-
derwent coronary artery bypass surgery during fol-
low-up were withdrawn at that time (i.e., censored).
With multivariate analysis of 18 clinical and seven
exercise parameters, the four that were found to be
independently predictive of mortality included: left
ventricular enlargement, congestive heart failure
score, ST segment response, and final exercise stage
achieved.
These investigators 21 also divided their patients
into some interesting subgroups for multivariate
analysis of clinical, exercise, and cardiac catheteriza-
tion variables. In those with preserved left ventricu-
lar function, the independent predictors of mortality
were: congestive heart failure score and peak exercise
heart rate in patients with single-vessel disease, con-
gestive heart failure score in patients with double-
vessel disease, and exercise capacity in patients with
triple-vessel disease. In the latter group-those with
preserved left ventricular function and triple-vessel
disease-survival was 100 % for those who exercised
to stage V (>15 METS) or greater in the Bruce pro-
tocol but only 53 % for those who could only achieve
stage l/2 (2 METS). In patients with poor left
ventricular function, exercise capacity was not a sig-
nificant predictor of survival. In their final multi-
variate survival model of all patients together,21
seven factors proved to be significant: left ventricu-
lar contraction pattern, number of diseased coronary
vessels, male gender, diuretic use, digitalis use, low
peak heart rate, and final exercise stage achieved.
Many of these factors, it should be noted, are either
directly or indirectly related to left ventricular func-
tion.
In a paper published in 1986,22 the same investiga-
tors looked at an additional subclassification of 5303
patients based on exercise capacity with respect to
medical versus surgical survival. It should be noted
that patients were not randomized into the treatment
categories and that patients in these categories were
by no means equivalent (i.e., the medically treated
patients had significantly greater prevalence of se-
vere congestive heart failure, prior acute myocardial,
digitalis therapy, and worse left ventricular function
by cardiac catheterization; the surgically treated pa-
tients had a higher prevalence of an ischemic ST re-
sponse to exercise, class 3 or 4 angina, and a lower
exercise capacity). After 7 years of follow-up, pa-
tients who had achieved < stage I (<5 METS) had a
 November 1991
1426 Morris et al. American Heart Journal

Table 1. Cardiovascular mortality

C” 0;
POP Mean v;, Study P; Pr 5% r,
Author Year size age Women Test type MI CHF Dig BB

Ellestad’ 1975 2761 50 18 TM Retro - --

Bruce12 1977 1852 53 0 TM Prosp - - - -

McNeer”j 1978 1472 - - TM Retro - - - -
Hammermeister15 1979 - 14 TM Retro - - - 100

Podrid’* 1981 142 57 0 TM Prosp 66 0 0 44 88

Kentlg 1982 147 49 10 Bike Prosp - - - 82

Bruce13 1983 4158 46 13 TM Prosp 0 0 0

Weinerzl 1984 - 23 TM Retro - - - - 100

Weinerz2 1986 5303 - 22 TM Retro 47 3 10 40 100

Dagenais25 1988 298 52 9 TM Retro 32 - - - 265

Weiner23 1987 1249 - 8 TM 60 5 13 44 100

Bogaty2” 1989 241 50 25 TM Retro 35 0 0 - -

Mark24 1989 2842 49 30 TM Prosp 29 4 -- - 100

SawadaeO 1990 170 53 48 TM Prosp 0 0 - - 0

Pr, prior; MI, myocardial infarction; CHF, congestive heart failure; Dig, digitalis; BB, /3-blockers; CAD, coronary artery disease; Cath, catheterization; FU,
follow-up; CABS, coronary artery bypass surgery; CV, cardiovascular; ExCap, exercise capacity; TM, treadmill; Retro, retrospective; Prosp, prospective; Chi
so; chi square analysis; KM, Kaplan-Meier; Ext, (Fisher) exact test; 3V, three-vessel; combo, combination; U, univariate; M, multivariate; Exp, expired.

significantly better survival with surgical therapy
(81% versus 78%, p = 0.04), especially if they also
had ST segment depression with exercise (82 % ver-
sus 72 % , p = 0.001). Those achieving > stage II (>8
METS) had equal survival with either therapy.
In 1987 Weiner et al.23 published a study that ex-
amined 1249 patients with triple-vessel disease who
again received either medical or surgical therapy. In-
dependent predictors of survival in this group were:
left ventricular score, final exercise stage achieved,
and treatment received (surgical versus medical). At
Duke University, Mark et al.24 in 1987 published a
significant prospective study of 2642 patients with
suspected coronary artery disease by history who re-
ceived both cardiac catheterization and a treadmill
test within 6 weeks of each other. The main result of
this study was the development of a treadmill score
that was highly predictive of survival, even when
considered with coronary anatomy and left ventric-
ular function. In the composition of this treadmill
score, after consideration of ST segment response,
(exercise capacity as determined by treadmill time
and treadmill angina index were the only other inde-
pendent predictors of mortality. In the final model,
treadmill exercise time had a relative weight of 1
compared with 4 for each of the other variables.
Dagenais et al. 25 retrospectively examined 298 pa-
tients with exercise tests exhibiting at least 2 mm of
ST segment depression who were treated medically.
They contrasted the survival in those with and with-
out exercise-induced angina. Of interest, not only did
they find that the silent ischemia group had a better
survival than the group with angina Cp = 0.05), but
they also concluded that survival in both groups was
Volume 122
Number 5 Prognostic value of exercise capacity 1427

% CAD Mean Range % cv Low ExCap High ExCap

Cath by FU FU % % FU % FU FU Study increases decreases
REQD Cath (Yr) (Yd FU CABS death death analysis mortality mortality

No - - 0.5-9.0 100 5.0 13.2 Life Chronotropic

table, incompetence
chi sq increases
mortality
No - 2.8 1.7-3.8 100 - 10.5 7.7 UN Yes
Yes 59 4.0 - 95 21.0 - - UN Yes
Yes 88 3.6 2.5-8.2 100 72 9.9 8.5 U,M, No, but only
cox 46% had TM
No 12 4.9 1.6-8.3 100 6.3 7.7 7.0 cox, Yes
life table
Yes - 2.4 - 81 2.7 5.4 5.4 KM No, x3V
disease
No n 6.1 - 93 - 2.6 1.0 UN Yes, In combo Chronotropic
with clinical incompetence
risk factor increases
mortality
Yes - - 3.0-5.0 99 36.0 5.2 4.3 U,M Yes, Exp
cox in 3V
disease
Yes - - 4.0-7.0 99 30.9 10.6 8.6 UM, Survival
cox, improved
chi sq by surgery
No 769 - 76.0 100 0 18 16 KM, Yes Yes
Cox, M
Yes - - 5.0-7.0 99 62.4 - - U&f, Poor Ex Cap
cox do better
with surgery
Yes 100 - 1.3-8.0 100 21.1 21.6 18.2 Yes Yes
Yes 61 5 -10.0 98 24.0 9.5 - Cox, KM, Yes Yes
Duke score
No 0 2.4 - 87 2.7 0 0 Fisher Yes
Ext,
t test

strongly correlated with exercise duration. (In the si-
lent ischemia group, survivors exercised 472 k 129
secondswhile nonsurvivors exercised 360 + 159 sec-
onds [p < 0.011.) Survival was nearly 100% in those
who reached 10 METS in either group. With multi-
variate analysis of the 194 patients who had also un-
dergone coronary angiography, only the presence of
multivessel disease and a low exercise duration were
predictive of decreased survival. A subsequent paper
published from the same institution, analyzing a
similar group of subjects, stated that exercise capac-
ity is predictive of survival but not of morbid events
including myocardial infarction or unstable angina.26
A summary of these studies is presented in Table I.
ALL-TYPE MORTALITY
The majority of studies previously cited do not
discuss the prediction of noncardiovascular mortal-
ity, and the majority of their survival data is based on
cardiac mortality only. Of the 52 deaths in the study
by Bogaty et al.,26only six were from medical causes
other than cardiac. Bruce et al. did not comment on
the extremely high percentage of noncardiac deaths
in both of their studies, 41% (80 of 195) of deaths in
197712and 63% (68 of 107) in 1983.13In their 1982
study, Dagenais et al.27reported only 5 of 54 deaths
(9%) being noncardiac, and in 1990 they25 again re-
ported only 3 of 32 deaths (9 % ) as being noncardiac.
Harris et a1.28reported only 14 of 259 deaths as non-
cardiac (5% ) in their study published in 1979 of 1214
patients with coronary artery diseaseby angiography
who were treated medically and followed for at least
1year. Kent et all9 had-only eight deaths over 2 years
of follow-up, all of which were cardiac. Weiner et al.
did not report any details of their noncardiac deaths
in any of their studies, but in the one published in
198421they did state that 18% (38 of 212) of the
deaths were in this category. So it would seem that

1428 Morris et al.
Table II. Survival in patients with a markedly positive (2 2
mm ST depression)exercisetest
5% 6 Year with Without exercise angina
METS exercise angina (silent ischemia)
213 loo”c 97
510 94% 87
r7 80 ‘7 64
15 44% 60
not only was there little interest in these noncardiac
deaths by these particular investigators, but they
have also reported wide ranges of incidence of these
events. Yet if the study groups are analyzed, it can be
seen that there was a range of 0 % to 10 % of noncar-
disc deaths in these patients with known coronary
disease. Cohorts such as that of the Seattle Heart
Watch study, published by Bruce et al. in 1983,13 in-
volved asymptomatic patients without known coro-
nary artery disease and consequently had a very high
incidence of noncardiac death (i.e., 63%).
It is important to know whether a low exercise ca-
pacity is predictive of all types of deaths, rather than
just those of cardiac origin. Without this information,
it is not possible to decipher whether other causes of
death have a relationship to exercise capacity (i.e.,
could comorbid conditions such as chronic obstruc-
tive pulmonary disease, cancer, malnutrition, etc., be
confounding the data so that in reality exercise
capacity is not predicting coronary artery disease
mortality itself?). If one is trying to predict cardiac
deaths, noncardiac deaths must be censored (i.e.,
follow-up terminated) and not be considered as an
actual end point. It must be understood that certain
conditions associated with noncardiac deaths could
also be limiting exercise capacity. A worse case sce-
nario, for instance, would be if a poor exercise capac-
ity is only predictive of death in cardiac patients with
these noncardiac-related conditions. Such questions
must be resolved for the optimal predictive use of
exercise testing.
MET LEVELS PREDICTIVE OF MORTALITY
Now that an overwhelming number of excellent
studies have determined that exercise capacity is an
independent risk factor for cardiac death, it must be
ascertained which MET levels can be used as cutoffs
to classify patients at increased risk. Many studies
have pronounced a low end of the spectrum, a MET
level below which survival is decreased. Bruce et al.
determined an exercise capacity of less than 3 METS
November 199 1
American Heart Jotwnal
in medically treated patients with coronary artery
disease to be predictive of increased sudden cardiac
-
death by multivariate analysis. When Dagenais et
a1.25 looked at their group of patients with “strongly
positive exercise ECGs,” they found exercise capac-
“;a
ity to be the only significant variable predicting sur-
“t
“;a vival. The nonsurvivors averaged an exercise dura-
% tion of 360 t 159 seconds (6 METS) for those with-
out exercise-induced angina and 247 rf. 98 seconds (5
METS) for those with such angina. Their survivors
had an exercise capacity averaging 472 +- 129 sec-
onds (8 METS) for those without angina and
344 ? 106 seconds (6 METS) for those with angina.
In their group of medically treated patients with cor-
onary artery disease, McNeer et a1.i6 determined that
an exercise capacity of less than or equal to stage I of
Bruce (less than 5 METS) predicted not only the
presence of significant coronary artery disease, but
also decreased survival. Exercise capacity did not
correlate with the absence of coronary artery disease
though; 47 % of their patients who achieved stage IV
Bruce (>13 METS) had significant coronary artery
disease. The most significant differences in survival
were noted in their patients with coronary artery
disease; those exercising to greater than stage IV
Bruce (13 METS) had a 24-month survival of 98%)
while those exercising less than stage I Bruce (<5
METS) had a survival rate of only 59 % over the same
period.
Podrid et al-l8 divided their patients with known
coronary disease into three groups based on exercise
time and found the group that exercised an average
of only 4.2 minutes (less than 6 METS) had a signif-
icantly lower survival rate after 6.7 years than the
other groups with a better exercise capacity. Of note,
they also found no significant difference in mortality
between the group with an average exercise time of
7.5 minutes (8 METS) and that with one of 10.2 min-
utes (11 METS).
Sawada et a1.,20 in their study of patient with nor-
mal exercise echocardiograms, found an exercise ca-
pacity of less than 6 METS to be predictive of
increased cardiovascular morbidity, but they had no
deaths during their mean follow-up of 2.4 months.
Weiner et a1.21 reported that in patients with pre-
served left ventricular function and triple-vessel dis-
ease, of those exercising to stage ‘/z Bruce (2 METS)
only 53 % survived 4 years, compared with 100 % for
those able to exercise to stage V Bruce or greater (>15
METS). In another group of patients with coronary
artery disease followed for 7 years, these inves-
tigators22 found that an exercise capacity of < stage
I Bruce (<5 METS) predicted a group with a higher
Volume 122
Number 5 Prognosticvalue of exercisecapacity 1429

Table Ill. Studies relating survival to MET levels

Author Year publ. No. subjects Subject population RX Results

Bruce12 1977 1852 Males with h/o CAD Med <5 METS predicts
increase in sudden
death
McNeer“j 1978 1472 Males and females, Med <5 METS predicts
59 % with and 41% significant CAD and
without CAD by angio Surg decreased survival
> 13 METS predicts
increased survival
>13 METS does not
predict absence of CAD
Podridls 1981 142 Males with h/o CAD Med <6 METS predicts
and positive TMET Surg decreased survival
No difference in survival
in those >8 METS
WeineG 1984 4083 Males and females Med <2 METS had 53%
with CAD by angio Surg 4-year mortality
(CASS criteria) >15 METS had 100%
4-year survival
Weiner22 1986 5303 Males and females Med <5 METS predicts
with CAD by angio Surg increased mortality and
(CASS criteria) benefit from CABS
210 METS predicts
equal survival with
either Med Rx or
CABS
Dagenais25 1988 298 Males and females Med Survivors with silent
with positive TMET ischemia averaged 8
METS
Nonsurvivors with silent
ischemia averaged 6
METS
Bogaty26 1989 241 Males and females Med <5 METS had 45%
with positive TMET S-year survival rate
>lO METS had 93%
S-year survival rate
Ma&24 1987 2842 Males and females Med Risk determined by
with CAD by history treadmill score
composed of ST
segment response,
exercise time, and
exercise angina score
Sawada20 1990 173 Males and females Med Normal Ex Echo and >8
METS predicts with
normal Ex Echo Surg
good prognosis
CABS, Coronary artery bypass surgery; CAD, coronary artery disease; CASS, Coronary Artery Surgery Study; h/o, history of; Med, medical treatment; 1
MET, metabolic equivalent = 3.5 ml Oz/kg/min; Rx, recommended treatment; angio, angiography; Surg, surgical treatment; ‘IMEl’, treadmill exercisetest,;
Ex, exercise; Echo, echocardiogram.

mortality and one that benefitted from coronary ar-
tery bypass surgery.
Though exercise capacity is inversely related to age
and activity status, only Bruce et al. have adjusted
their data for age and activity level (creating the
Functional Aerobic Impairment [FAI] classification).
Doing so may give physicians a better “handle” on
prognosis. A good approach would be to utilize
receiver operating characteristic (ROC) curves to
determine for different age groups the most efficient
MET cutpoint levels for identifying high risk.
A summary of the significant MET levels relating
to mortality is presented in Tables II and III. It is
important to note that age, activity level, or compli-

1430 Morris et al.
eating illnesses have not been considered in these
studies. Age could be considered in several ways: (1)
norms by decade, considering the lowest tenth per-
centile as abnormal; (2) the derivation of an aerobic
impairment scale based on age; and (3) the inclusion
of age in a multivariate equation. For instance, it is
difficult to believe that a 5 MET threshold conveys
the same risk for death in a 40-year-old (11 METS
mean for this decade) as in a 70-year-old (7 METS
mean for this decade) or in a patient with debilitat-
ing chronic obstructive pulmonary disease. Optimal
use of exercise capacity as a risk predictor requires
that we understand confounders so that appropriate
MET thresholds can be chosen for appropriate clin-
ical subgroups.
SUMMARY
While there is still much debate in the literature
regarding the specific MET levels at which there are
differences in survival, the following points have be-
come clear with the growing body of reports in the
literature. Exercise capacity seems to be an indepen-
dent predictor of mortality, and when it is combined
with other clinical, exercise, or angiographic data, it
becomes very powerful in this regard. This relates to
both overall mortality and to that from cardiovascu-
lar disease. There is still a need for the establishment
of mortality data related to MET levels adjusted for
age and activity status.
A low exercise capacity of less than 6 METS indi-
cates a higher mortality group, probably regardless of
the underlying extent of coronary disease or left ven-
tricular function, Analysis of the CASS data has in-
dicated that these patients benefit from coronary ar-
tery bypass surgery with respect to survival. An ex-
ercise capacity of greater than 10 METS designates
an excellent survival group, again despite the extent
of coronary artery disease or left ventricular function.
If 10 METS truly exerts a “protective effect” that
obviates any survival benefit from coronary artery
bypass surgery, this has enormous implications for
cost containment and medical care. It is nonetheless
important to remember thatthis level of exercise ca-
pacity does not imply the absence of either coronary
disease or triple-vessel coronary disease.
Exercise capacity is related to more than just car-
diovascular fitness and integrity. It is dependent
upon a combination of other physiologic components
as well, including pulmonary function, health status
of other organ systems, nitrogen balance, nutritional
status, medications, orthopedic limitations, and oth-
ers. Nonetheless, exercise capacity has been estab-
lished as a powerful predictor of survival and de-
November 199 1
Americiln Heart Journal
serves equal emphasis with that of ST segment
interpretation in the evaluation of exercise test
responses.
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2. American College of Sports Medicine. Guidelines for exercise
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3. Froelicher VF. Exercise and the heart: Clinical concepts. Chi-
cago: Yearbook Medical Publishers, Inc, 1987.
4. Jette M, Sidney K, Blumchen G. Metabolic equivalents
(METS) in exercise testing, exercise prescription, and evalu-
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assessment for primary coronary heart disease events by max-
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Volume 122
Number 5 Prognostic value
testing in identifying patients with improved survival after
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Constrictive pericarditis versus restrictive
cardiomyopathy: A reappraisal and update of
diagnostic criteria
Paul T. Vaitkus, MD, and William G. Kussmaul, MD. Philadelphia, Pa.
The difficulty in distinguishing between constrictive
pericarditis and restrictive cardiomyopathy has been
the subject of numerous reports and reviews. Despite
the application of a variety of available criteria, some
patient’s conditions still confound attempts at diag-
nosis. Reviews and standard textbooks of cardiology
have commented on the limitations of invasive he-
modynamic criteria, l-5 but none has quantitatively
examined the accuracy of these criteria since the re-
port of Wood6 three decades ago. Furthermore, in
recent years a number of reports have described new
methods for distinguishing these two conditions. The
purposes of this review are: (1) to critically examine
the hemodynamic criteria applied in the effort to
separate these two groups of patients; (2) to review
the current status of noninvasive testing and myo-
cardial biopsy in these conditions; and (3) on the ba-
sis of the data presented, to develop a clinical algo-
From the Cardiovascular Division, Hospital of the University of Pennsyl-
vania.
Received for publication March 18, 1991; accepted May 7, 1991.
Reprint requests: Dr. William Kussmaul, Cardiovascular Division, F.9.121,
Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia,
Pa 19104.
4/1/32453
of exercise capacity
painless strongly positive exercise electrocardiogram. Am J
Cardiol 1988;62:892-5.
26. Bogaty P, Dagenais GR, Cantin B, et al. Prognosis in patients
with a strongly positive exercise electrocardiogram. Am J
Cardiol 1983641284-8.
27. Dagenais GR, Rouleau JR, Christen A, Fabia J. Survival of
patients with a strongly positive exercise electrocardiogram.
Circulation 1982;65:452-6.
28. Harris PJ, Harrell FE, Lee KL, et al. Survival in medically
treated coronary artery disease. Circulation 1979;60:1259-69.
rithm that can be applied when either constrictive or
restrictive disease is suspected.
HEMODYNAMIC CRITERIA
The first recording of intracardiac hemodynamic
measurements in constrictive pericarditis were per-
formed in 1946 by Bloomfield et al? Subsequently,
Hansen et al.s described the classic“dip and plateau”
or “square root” appearance of the diastolic tracing
in constriction. Later studies demonstrated similar
recordings in restrictive cardiomyopathy.g Three
well-known hemodynamic criteria for distinguishing
the two conditions are: (1) Equalization (difference
a5 mm Hg) of right ventricular (RV) end-diastolic
pressure (RVEDP) and left ventricular (LV) end-di-
astolic pressure (LVEDP) favors constriction. (2)
Constriction is more often associated with modest
elevations of RV systolic pressure (550 mm Hg),
whereas in restriction RV systolic pressures fre-
quently exceed 50 mm Hg. (3) Constriction is associ-
ated with RVEDP exceeding one third the RV
systolic pressure, whereas in restriction the ratio is
characteristically less than one third.’ The first cri-
terion was proposed by Wood6 and the latter two cri-
teria were first articulated by Yu et al.l”
Wood6 evaluated the ability of equalization of
LVEDP and RVEDP to distinguish constriction
1431