Download Exercise Capacity in Patients with Severe Left Ventricular Dysfunction

Exercise Capacity in Patients
with Severe Left Ventricular Dysfunction
WILLIAM BENGE, M.D., ROBERT L. LITCHFIELD, D.O.,
AND
MELVIN L. MARCUS, M.D.
SUMMARY Normal or near-normal exercise capacity has been thought to reflect normal left ventricular
function. Many compensatory mechanisms could preserve exercise capacity in patients with severe left ventricular dysfunction. We evaluated exercise capacity using a treadmill exercise test in 26 patients with severe
left ventricular dysfunction defined by a left ventricular ejection fraction of 30% or less by isotope ventriculography. One half of the patients had normal exercise capacity and a normal cardiothoracic ratio on
chest x-ray. This study indicates that traditional predictors of left ventricular function that have been widely
used in clinical evaluation of the patients with cardiac disease (cardiothoracic ratio and exercise capacity) can
be normal in a significant number of patients with severe left ventricular dysfunction. Thus, left ventricular
function cannot be accurately estimated using these traditional predictors and should be assessed quantitatively. The isotope ventriculogram appears to be ideal for this purpose.
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City Veterans Administration Hospital who had an
ejection fraction of 30% or less and who also had a
graded treadmill exercise test during the 24-month
period from February 1977 through February 1979.
Patients were excluded from the study if a major
change in therapy (medical or surgical) was instituted
between the two tests. The interval between the tests
was 0.9 ± 1.5 weeks (mean ± SD).
The study included 26 patients, 20 men and six
women, ranging in age from 30-76 years (56 ± 15
years, mean ± SD). In 23 patients the cardiac
diagnosis was coronary artery disease as defined by: 1)
the presence of abnormal Q waves (2 0.04 second
duration) and a history of myocardial infarction; 2)
coronary arteriography with greater than 70% stenosis
in at least one major coronary vessel; or 3) a left ventricular aneurysm on isotope ventriculogram or left
ventricular contrast angiography. The remaining three
patients had cardiomyopathy with diffuse left ventricular dysfunction. Coronary arteries were normal in
one patient and not studied in the last two patients.
Among the 26 study patients, nine had cardiac
catheterization within 3 months of the treadmill or
isotope ventriculogram with no intervening changes in
medical or surgical management. To further assess the
accuracy of the isotope ventriculogram in evaluating
left ventricular ejection fraction, 29 patients with a
variety of heart diseases were also reviewed retrospectively. These 29 were consecutive patients in whom
both contrast left ventricular angiography and isotope
ventriculogram determination of ejection fraction had
been performed. Patients were excluded if either study
was technically inadequate or if atrial fibrillation was
present.
Eighteen normal, healthy male subjects ranging in
age from 17-22 years had an isotope ventriculogram.
The evaluation of these normal subjects was approved
by the Human Use Committee of the University of
Iowa Hospitals, and informed consent was obtained
from each subject.
IN PATIENTS with suspected or established cardiac
disease, normal or near-normal exercise capacity has
generally been thought to reflect normal left ventricular function. The rationale for this assumption is
based on studies that have shown a close linear correlation between maximal oxygen consumption and
cardiac output.1-4 Furthermore, the assumption that
exercise capacity relates to the severity of heart disease has formed the basis of the most commonly used
clinical classification of patients with heart disease
(New York Heart Association).
Although left ventricular dysfunction may alter exercise capacity, many compensatory mechanisms
could preserve exercise tolerance despite severe left
ventricular dysfunction, including preservation of absolute stroke volume, chronotropic competence, increased oxygen extraction, altered left ventricular
compliance or augmented pulmonary lymphatic flow.
Therefore, we reevaluated exercise capacity in patients
with severe left ventricular dysfunction. If a substantial number of patients with severe left ventricular
dysfunction and near-normal exercise tolerance could
be identified, the concept that exercise capacity is a
predictor of left ventricular performance would be
challenged.
Methods
Patient Selection
This study was a retrospective analysis of patients
referred to the University of Iowa Hospitals and Iowa
From the Cardiology Division and the Cardiovascular Center,
Department of Internal Medicine, University of Iowa Hospitals and
Clinics, and the Veterans Administration Hospital, Iowa City,
Iowa.
Supported by Research Career Development Award HL00328,
program project grant HL14388, and grant RR-59 from the
General Clinical Research Center Program, Division of Research
Resources, NIH.
Address for correspondence: Melvin L. Marcus, M.D., Associate
Professor, Department of Internal Medicine, Cardiovascular Division, University of Iowa Hospitals and Clinics, Iowa City, Iowa
55242.
Received March 19, 1979; revision accepted November 15, 1979.
Circulation 61, No. 5, 1980.
Cardiac Imaging Procedures
Gated isotope ventriculograms were obtained in all
patients. Technetium-99m-labeled human red cells or
955
CIRCULATION
956
human serum albumin (20 mCi) was used as the imaging agent. Images were obtained with a Picker 1680
Dyna camera with an all-purpose collimator. The
energy window was centered at 140 keV with a width
of 20%. The images were constructed from about 300
cardiac cycles recorded over 3-5-minute periods with
the patient at supine rest. Data were collected with a
Medical Data Systems computer and a left ventricular
ejection fraction was calculated from the left anterior
oblique projection using a method described by Burow
et al.5 None of the patients had significant ventricular
ectopy during isotope ventriculography.
Contrast Left Ventricular Angiography
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All cardiac catheterizations were performed for
diagnostic purposes. Single-plane left ventricular
angiograms were obtained in a 300 right anterior
oblique position. Angiograms were obtained with a
power injection of 40-60 ml of Renographin-76 (meglumine diatrizoate) and recorded on 35-mm film at 60
frames/sec. Ejection fraction was calculated using the
area-length method of Kennedy.6
Treadmill Exercise Testing
All patients performed graded treadmill exercise
tests according to the Sheffield protocol, that is, to include stage 0 and stage 1/2, both 3 minutes long.7 All
exercise tests were monitored by a physician and a 12lead ECG was recorded before, during and after exercise. End points for exercise included dyspnea, fatigue
or attainment of 85% of the predicted maximum heart
rate. Thus, we did not determine maximum exercise
capacity in all patients. Exercise duration longer than
11 minutes was considered normal.8
Cardiac Medications
There were no major alterations in clinical status or
in therapy (medical or surgical) between the isotope
ventriculogram and treadmill exercise testing.
Medications at the time of the studies included: 1)
digoxin (n 19); 2) diuretics (n 15); 3) propranolol
(n= 3); 4) long-acting nitroglycerin preparations
(n 8); 5) quinidine (n = 3); and 6) procainamide
=
=
=
(n= 1).
Normal EF = 70%
Ant.
LAO
VOL 61, No 5, MAY 1980
Cardiothoracic Ratio
Twenty-five of 26 patients had chest x-rays
available for evaluation. The cardiothoracic ratio was
obtained using a standard 6-foot posteroanterior
roentgenogram at full inspiration. Cardiac size was
measured as the distance between vertical lines
parallel to the right and left heart borders and was
divided by the widest horizontal distance from the
right to left inner rib margins. A cardiothoracic ratio
greater than 0.50 was considered evidence of cardiomegaly.9 The chest x-rays were also evaluated for
evidence of pleural effusion or pulmonary congestion,
defined as redistribution of blood flow to the upper
lobes, presence of Kerly B lines or perihilar infiltrates.
Results
Accuracy of Ejection Fractions
Determined by Isotope Ventriculogram
Figure 1 depicts anterior and left anterior oblique
isotope ventriculogram images at end-systole and enddiastole from a normal subject and in two patients.
The ejection fractions of these patients represent the
extremes of ejection observed in the study group
(6-30%), and the isotope ventriculogram from a normal subject (70%).
To assess the accuracy of isotope ventriculogram
determination of ejection fraction, the isotopedetermined ejection fraction was compared with the
contrast angiogram-determined ejection fraction
among nine study patients and 29 other patients with a
variety of heart diseases (fig. 2). A close correlation
(r 0.88) between ejection fractions determined by
these two methods was observed over a wide range
(6-80%) and among the study patients as a subgroup
(r = 0.74). The mean interval between the isotope and
angiographic measurement of ejection fraction was
4.8 + 4.2 weeks.
The left ventricular ejection fractions in the study
patients and normal subjects were compared. The
highest ejection fraction in the study group was nearly
5 standard deviations below the mean ejection fraction
of the normal subjects. Thus, the study patients had
severely decreased left ventricular ejection fractions.
Abnormal EF = 30%
Ant
LAfl
Abnormal EF = 6%
Ant
[Diastole
Systole
FIGURE 1. Anterior (Ant.) and left anterior oblique (LAO) isotope ventriculogram images at end-systole
and end-diastole from a normal subject with an ejection fraction (EF) of 70% (left panel), a subject with an
EF of 30% (center panel) and a subject with an EF of6% (right panel). White arrows point to the left ventricle (L V) and the dark arrows to the interventricular septum in the LA 0 projection.
EXERCISE AND LV DYSFUNCTION/Benge et al.95
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FIGURE 2. Comparison of contrast-angiogram-determined
ejection fraction and isotope ventriculogram ejection fraction in 29 patients (closed circles) with a variety of heart diseases over a wide range of ejection fractions and nine study
patients (open circles). Correlation coefficient for the subgroup of study patients was r = 0.74.
Comparison of Treadmill Performance
and Isotope Ventriculogram Ejection Fractions
Resting heart rate and blood pressure, obtained
during the treadmill test and the isotope ventriculo-
gram, were similar. Figure 3 compares left ventricular
ejection fraction to treadmill exercise duration. About
half of these patients exercised into a normal range.
Thus, in some patients with poor left ventricular function, exercise capacity can be well preserved.
Comparison of Ejection Fraction and Cardiothoracic Ratio
Figure 4 is a comparison of the cardiothoracic ratio
30 r-
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Normal Esercise Capacity
6
18
9
12
15
Exercise Duration (Sheffield Protocol)
FIGURE 3. Comparison ofleft ventricular ejection fraction
and the duration of treadmill exercise among patients with
poor left ventricular function. The maximum left ventricular
ejection fraction among the study group is 30%.
0.7
0.6
0.5
Cardiothoracic Ratio
FIGURE 4. Comparison of cardiothoracic ratio and ejection fraction. The arrow notes a patient whose cardiothoracic ratio was 0.46, whose duration of exercise was
15.5 minutes, and yet whose ejection fraction tvas 14%.
0.3
0.4
and ej.ection fraction. The ejection fraction was not
closely correlated to cardiothoracic ratio (r = 0.30).
Thirty-eight percent had other roentgenographic signs
suggesting left ventricular failure (venous congestion
and pleural effusion). The data point marked by the
arrow in figure 4 is from a patient whose cardiothoracic ratio was 0.46 and whose duration of exercise on graded treadmill was 15.5 minutes. His ejection fraction was 14%. Thus, a patient with suspected
or established cardiac disease with normal heart size
and normal exercise capacity can have severely
decreased left ventricular function.
Discussion
We conclude from this study that exercise capacity
and the chest x-ray are normal in many patients with
severe left ventricular dysfunction. We will focus on
three aspects of this investigation: validity of the
isotope ventriculogram, limitations of the study and
possible explanations for our findings.
Isotope Ventriculogram
Over a wide range, left ventricular ejection fraction
measured with the isotope ventriculogram correlates
closely (r = 0.88) with values obtained with contrast
angiography, although in patients with ejection fractions less than 30% the correlation coefficient was only
0.74. There is no reason to suspect that these patients
don't have left ventricular dysfunction. Also, the
isotope measurements of ejection fraction have been
shown to be highly reproducible. 10-12 Thus, the isotope ventriculogram accurately measures the left ventricular ejection fraction.
An important assumption critical to the interpretation of the data is that left ventricular ejection fraction
is a valid index of left ventricular performance. Two
major lines of evidence support this assumption. First,
the left ventricular ejection fraction compares
favorably with the combination of other indexes of left
ventricular performance such as Vmax, end-diastolic
958
CI RCULATION
pressure, contraction pattern, and velocity of contractile element shortening.13 Second, various studies have
emphasized the prognostic significance of the left ventricular ejection fraction in patients with coronary
artery disease, valvular heart disease and cardio-
myopathy.14-l9
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Limitations of the Study
Our conclusions are based on data obtained from
referred patients with coronary artery disease optimally treated with digitalis, diuretics and vasodilators. Therefore, extrapolating our findings to patients
with various untreated cardiac ailments would be
inappropriate even if the severity of left ventricular
dysfunction were similar.
Also, our study group had a narrow range of ejection fractions, which could obscure a positive
relationship between exercise duration and left ventricular ejection fraction. When exercise duration in
patients with a wide range of ejection fractions was examined, Paine and co-workers20 observed a significant
direct relationship. However, in the 14 patients in
Paine's study with low ejection fractions (< 30%), exercise capacity was variable.
Normal exercise in sedentary individuals as established by Bruce2' is at a relatively low level of oxygen consumption compared with the maximal oxygen
consumption reached among trained athletes22 (41
ml/kg * mm of 02 vs 61 ml/kg . mm of 02, respectively). Thus, although our patients could exercise into
the normal range as defined by Bruce, their maximal
exercise capacity after training would probably be less
than that of a normal trained subject.
Possible Mechanisms for Preservation of Exercise Capacity
Several mnechanisms can preserve exercise capacity
despite severe left ventricular dysfunction. These include preservation of absolute stroke volume,
maintenance of chronotropic responsiveness, increased oxygen extraction, augmented pulmonary
lymphatic flow and altered left ventricular compliance.
Preservation of stroke volume via an increase in left
ventricular end-diastolic volume as seen in patients
with coronary artery disease23' 24 may be important in
maintaining volume exercise capacity in some of the
study patients. Furthermore, left ventricular volume
has also been shown to increase with upright exercise.25
Tachycardia can also maintain cardiac output in a
failing ventricle. Although some patients with coronary disease have chronotropic incompetence,26 at
peak exercise, heart rate responses in our patients
averaged 134 + 37 beats/min and one-third achieved
85% of their predicted maximum rate.
Increased oxygen extraction27' 28 during exercise is
common in patients with coronary disease.29 Elevated
2, 3 DPG levels or local tissue acidosis30 may facilitate
oxygen extraction in these patients.
Enhanced pulmonary lymphatic flow could increase
exercise capacity by limiting the pulmonary conges-
VOL 61, No 5, MAY 1980
tion associated with pulmonary venous hypertension.
This has been demonstrated in an animal model.31
Finally, chronic alterations in diastolic compliance
of the left ventricle can limit increases in filling
pressure during exercise. This would prevent
pulmonary congestion and increase exercise capacity.
Prospective hemodynamic studies in patients
similar to those in our study group are ongoing.32
Preliminary results in a subgroup with low ejection
fraction (mean 17 ± 3%) and normal exercise capacity
(exercise duration 13.6 ± 7 minutes [Sheffield
protocol]) have shown an impressive tolerance of high
pulmonary capillary wedge pressures (mean 33 mm
Hg) during supine exercise without limiting dyspnea.
With upright exercise stroke volume increased (40%),
heart rate increased (70%), cardiac output increased
threefold, and peripheral vascular resistance
decreased substantially (60%). Thus, several compensatory mechanisms contributed to the preservation of
exercise capacity in these patients.
In conclusion, among patients with severely
decreased left ventricular function, exercise capacity
can be variable and is a poor predictor of left ventricular performance. While exercise testing provides
valuable information about the integrated response to
exercise, one should seek a more reliable and direct
assessment of left ventricular performance than can be
provided by exercise testing or the chest x-ray. Noninvasive evaluation of left ventricular function with the
isotope ventriculogram appears to be ideal for this
purpose.
Acknowledgment
We thank Marcia Miller, Valorie Vaughan and Victor Wedel for
their technical assistance, Drs. Francois M. Abboud, Allyn L. Mark
and Richard Kerber for their thoughtful review of this manuscript,
and Debbie Mansure and Karen Kinney for their expert secretarial
assistance in the preparation of this manuscript.
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Exercise capacity in patients with severe left ventricular dysfunction.
W Benge, R L Litchfield and M L Marcus
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Circulation. 1980;61:955-959
doi: 10.1161/01.CIR.61.5.955
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