Download Pulmonary Function in Patients With Reduced Left Ventricular

Pulmonary Function in Patients With
Reduced Left Ventricular Function*
Influence of Smoking and Cardiac Surgery
Bruce D. Johnson, PhD; Kenneth C. Beck, PhD; Lyle J. Olson, MD;
Kathy A. O’Malley; Thomas G. Allison, PhD; Ray W. Squires, PhD; and
Gerald T. Gau, MD, FCCP
Study objective: The impact of stable, chronic heart failure on baseline pulmonary function
remains controversial. Confounding influences include previous coronary artery bypass or valve
surgery (CABG), history of obesity, stability of disease, and smoking history.
Design: To control for some of the variables affecting pulmonary function in patients with chronic
heart failure, we analyzed data in four patient groups, all with left ventricular (LV) dysfunction
(LV ejection fraction [LVEF] < 35%): (1) chronic heart failure, nonsmokers, no CABG (n ⴝ 78);
(2) chronic heart failure, nonsmokers, CABG (n ⴝ 46); (3) chronic heart failure, smokers, no
CABG (n ⴝ 40); and (4) chronic heart failure, smokers, CABG (n ⴝ 48). Comparisons were made
with age- and gender-matched patients with a history of coronary disease but no LV dysfunction
or smoking history (control subjects, n ⴝ 112) and to age-predicted norms.
Results: Relative to control subjects and percent-predicted values, all groups with chronic heart
failure had reduced lung volumes (total lung capacity [TLC] and vital capacity [VC]) and expiratory
flows (p < 0.05). CABG had no influence on lung volumes and expiratory flows in smokers, but
resulted in a tendency toward a reduced TLC and VC in nonsmokers. Smokers with chronic heart
failure had reduced expiratory flows compared to nonsmokers (p < 0.05), indicating an additive
effect of smoking. Diffusion capacity of the lung for carbon monoxide (DLCO) was reduced in smokers
and in subjects who underwent CABG, but not in patients with chronic heart failure alone. There was
no relationship between LV size and pulmonary function in this population, although LV function
(cardiac index and stroke volume) was weakly associated with lung volumes and DLCO.
Conclusions: We conclude that patients with chronic heart failure have primarily restrictive lung
changes with smoking causing a further reduction in expiratory flows.
(CHEST 2001; 120:1869 –1876)
Key words: expiratory airflow; heart failure; spirometry; vital capacity
Abbreviations: ACE ⫽ angiotensin-converting enzyme; BMI ⫽ body mass index; CABG ⫽ coronary artery bypass or valve
surgery; CAD ⫽ coronary artery disease; Dlco ⫽ diffusing capacity of the lung for carbon monoxide; FEF ⫽ forced
expiratory flow; FEF25 ⫽ forced expiratory flow at 25% of VC; FEF50 ⫽ forced expiratory flow at 50% of VC;
FEF75 ⫽ forced expiratory flow at 75% of VC; LV ⫽ left ventricular; LVEF ⫽ left ventricular ejection fraction;
MVV ⫽ maximal voluntary ventilation; PEF ⫽ peak expiratory flow; PFT ⫽ pulmonary function test; RV ⫽ residual volume;
TLC ⫽ total lung capacity; Va ⫽ alveolar volume; VC ⫽ vital capacity
linked in series with the cardiac
T hepump,lungsandarethey
are not only influenced by
mechanical alterations in pump function but likely by
*From the Divisions of Cardiovascular (Drs. Johnson, Olson,
Allison, Squires, and Gau, and Ms. O’Malley) and Thoracic
Diseases (Dr. Beck), Department of Internal Medicine, Mayo
Clinic and Foundation, Rochester, MN.
This work was supported in part by the Mayo Clinic and Foundation, and Human Health Services grant MO1-RR00585, General
Clinical Research Centers, Division of Research Resources, National Institutes of Health.
Manuscript received March 23, 2001; revision accepted June 19,
2001.
Correspondence to: Bruce D. Johnson, PhD, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, 200 First St,
SW, Rochester MN 55905; e-mail: [email protected]
neurohumoral modulators and cytokines involved in
the pathogenesis of heart failure.1– 4 Multiple studies5–18 have been published describing pulmonary
function-related changes in patients with chronic left
ventricular (LV) dysfunction. These studies have
varying conclusions concerning the influence of
heart failure on resting pulmonary function, ranging
from essentially normal values, to primarily restrictive changes, to combined restrictive and obstructive
changes.6,9,10,14,19 –22 There are many confounding
influences in these previous studies that may influence pulmonary function independent of changes
due to heart failure alone. These include changes
due to normal aging, obesity, and environmental
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1869
exposure (primarily tobacco products) or to other
disease processes (eg, asthma).23 Many previous
studies have also included patients who have undergone coronary artery bypass surgery or valve surgery
(CABG) that may influence lung and chest wall
function for a number of reasons.6 The focus of the
present study was to assess pulmonary function in
patients with a history of stable, reduced LV function
in relationship to smoking history and previous thoracic surgery to try to understand the influences of
heart failure “alone” on lung and chest wall function.
Materials and Methods
Subjects
A retrospective analysis was performed on data from heart
failure patients obtained from databases maintained by the
Cardiovascular Health Clinic (a preventive and rehabilitative
cardiac clinic of the Mayo Clinic) and the Heart Failure Clinic at
the Mayo Clinic, Rochester, from 1994 to 1998. Heart failure
included patients with histories of dilated and ischemic pathologic conditions and with ejection fractions ⱕ 35% with and
without a history of CABG. A body mass index (BMI) of ⬎ 35
kg/m2 was also used to exclude morbidly obese subjects. Pulmonary function test (PFT) results for patients were obtained from
the database of the Pulmonary Function Laboratory at Mayo for
spirometry, plethysmographic total lung capacity (TLC), and
diffusing capacity of the lung for carbon monoxide (Dlco). The
PFTs were obtained within a 2-month period from the determination of LV ejection fraction (LVEF). Ejection fraction data
were obtained primarily from echocardiography, but were also
obtained by radionuclide angiography and first pass with Sestamibi. The reason PFTs had been ordered on the chronic heart
failure patients varied considerably. Many had been ordered
simply as a part of their clinical workup or follow-up, some for
dyspnea that was believed to be out of proportion to the degree
of LV dysfunction, and others to rule out asthma, screening for
inclusion into research studies, presurgical workup, as well as
smoking history. Control subjects included individuals with a
history of documented coronary artery disease (CAD) [previous
angioplasty, small or non-Q-wave myocardial infarction, evidence
of ischemia on an imaging study] but with a normal LVEF
(⬎ 50%) and no previous thoracic surgery or smoking history.
Most of these subjects were sent for PFTs for reasons that were
similar to the chronic heart failure population. To be included in
the nonsmoking group, subjects had to have never smoked. For
the smokers, a ⬎ 5-pack-year history was set as the minimum
criterion. Five groups were compared: (1) chronic heart failure,
nonsmokers, no CABG; (2) chronic heart failure, nonsmokers,
CABG; (3) chronic heart failure, smokers, no CABG; (4) chronic
heart failure, smokers, CABG; and (5) control subjects. All
subjects involved in the study signed releases allowing the use of
clinical records for investigational purposes.
Measurements
Pulmonary function measurements included an assessment of
lung volumes (TLC, vital capacity [VC], FVC, residual volume
[RV], and FEV1), and an assessment of expiratory flows (peak
expiratory flow [PEF], forced expiratory flow [FEF], FEF at 25%
of VC [FEF25], FEF at 50% of VC [FEF50], and FEF at 75% of
VC [FEF75], respectively). Also included was the mean flow
between 25% and 75% of FVC. Subjects also performed maximal
voluntary ventilation (MVV) maneuvers for 12 s and single-breath
Dlco. Spirometry and Dlco data were collected in accordance
with American Thoracic Society standards.24 From the flow and
volume data, mean expiratory maximal flow-volume envelopes
were plotted for visual comparison between the various groups.
Significant differences between groups were obtained with analysis of variance (p ⬍ 0.05), and subsequent post hoc analyses
were performed using t tests.
In all patients with chronic heart failure for whom echocardiograms were available (n ⫽ 119), measurements were made of
cardiac dimensions (LV end-diastolic diameter, LV end-diastolic
posterior wall thickness, left atrial diameter) and cardiac function
(stroke volume, cardiac index, and right ventricular pressures)
and were obtained for correlational relationships with pulmonary
function measurements.
Results
Subject Characteristics
Mean characteristics of the five groups are shown
in Table 1. No significant differences were observed
among the groups for age, height, weight, or BMI.
LVEF did not differ among the groups with chronic
heart failure (averaging 23%), but as designed was
significantly reduced relative to the CAD control
subjects. Smoking history was not different between
Table 1—Subject Characteristics*
Groups†
1
2
3
4
5
Age, yr
Subjects,
No./Female
Gender, %
Height, cm
Weight, kg
BMI, kg/m2
Smoking,
Pack-yr
LVEF,
%
63 ⫾ 2
66 ⫾ 2
67 ⫾ 2
67 ⫾ 2
65 ⫾ 2
78/34
46/25
40/30
48/26
112/31
170 ⫾ 1
171 ⫾ 1
172 ⫾ 2
171 ⫾ 1
168 ⫾ 2
81 ⫾ 3
77 ⫾ 2
79 ⫾ 2
81 ⫾ 3
82 ⫾ 2
28.4 ⫾ 0.85
27.9 ⫾ 0.69
27.8 ⫾ 0.79
28.5 ⫾ 0.84
29.0 ⫾ 0.43
0
0
46 ⫾ 3‡
54 ⫾ 4‡
0
23 ⫾ 1§
23 ⫾ 1§
23 ⫾ 1§
21 ⫾ 1§
61 ⫾ 1
*Data are presented as mean ⫾ SE.
†Group 1 ⫽ chronic heart failure, nonsmokers, no CABG; group 2 ⫽ chronic heart failure, nonsmokers, CABG; group 3 ⫽ chronic heart failure,
smokers, no CABG; group 4 ⫽ chronic heart failure, smokers, CABG; group 5 ⫽ control subjects.
‡Smokers (groups 3 and 4) different from nonsmokers (groups 1 and 2 (p ⬍ 0.05).
§Heart failure patients (groups 1 to 4) different from control subjects (group 5) (p ⬍ 0.05).
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Clinical Investigations
smokers with previous CABG vs smokers with no
previous CABG (p ⬎ 0.05). There was a tendency
for a greater number of female patients (percent) in
the chronic heart failure nonsmokers and smokers
with no previous CABG, as well as in the control
group vs the other groups. There were no differences in medications in the groups with chronic
heart failure, with the majority of patients receiving
angiotensin-converting enzyme (ACE) inhibitors, diuretics, digoxin, and aspirin. Most CAD control
subjects were receiving aspirin, statin, and variable
additional medications, ranging from no additional
medications to use of ␤-blockers, calcium-channel
blockers, ACE inhibitors, and diuretics.
Lung Volumes
Mean lung volumes for each group are shown in
Table 2. TLC, VC, FVC, and FEV1 were all significantly reduced in the groups with chronic heart
failure relative to the control group (p ⬍ 0.05). Nonsmokers with a history of CABG tended to have the
greatest reduction in TLC relative to control subjects
and the other groups with chronic heart failure
(p ⬍ 0.05). Smokers tended to have a greater reduction in VC, FVC, and FEV1/FVC relative to nonsmokers and an elevated RV/TLC ratio (p ⬍ 0.05).
The RV/TLC ratio did not differ between nonsmokers with chronic heart failure and the CAD control
subjects.
Expiratory Flows
Table 3 lists average expiratory flows for each
group. PEF was reduced slightly in the smokers with
chronic heart failure relative to control subjects but
not in nonsmokers with chronic heart failure. All
other expiratory flows were reduced significantly in
all groups with chronic heart failure, but were
reduced to a greater extent in the smokers compared
to nonsmokers (p ⬍ 0.05). No differences were observed between subjects who underwent previous
CABG vs those who did not. Interestingly, MVV did
not differ among groups with chronic heart failure,
but was significantly reduced relative to the CAD
control subjects (p ⬍ 0.05).
Mean Maximal Flow-Volume Curve
Figures 1–3 are mean expiratory flow-volume
curves plotted relative to the percent-predicted
TLC. Figure 1 emphasizes the changes observed in
the patients with chronic heart failure alone with no
history of smoking or previous CABG, relative to the
CAD control subjects and predicted values. Figure 2
emphasizes the groups with chronic heart failure
with previous CABG relative to the groups with
chronic heart failure without previous CABG compared to predicted values. Figure 3 shows the influence of smoking on lung volumes and flow rates
relative to the nonsmoking patients.
DLCO and Alveolar Volume
Mean values for Dlco and alveolar volume (Va)
are shown in Table 4. No differences were noted in
Dlco between the control group and groups with
chronic heart failure alone; however, significantly
lower values were observed in the patients with
chronic heart failure with previous CABG and in
patients with a smoking history (p ⬍ 0.05). Va and
Dlco/Va also tended to be lower in patients with
chronic heart failure and a history of CABG, as well
as in patients with a history of smoking.
Table 2—Lung Volumes*
Groups
1
2
3
4
5
TLC, L
(% Predicted)
VC, L
(% Predicted)
FVC, L
(% Predicted)
FEV1, L
(% Predicted)
5.54 ⫾ 0.17
(92 ⫾ 3)†
5.39 ⫾ 0.16
(86 ⫾ 3)†‡
5.87 ⫾ 0.17
(92 ⫾ 3)†
5.66 ⫾ 0.17
(92 ⫾ 2)†
6.06 ⫾ 0.16
(100 ⫾ 2)
3.30 ⫾ 0.12
(84 ⫾ 2)†
3.18 ⫾ 0.11
(81 ⫾ 2)†
3.22 ⫾ 0.10
(78 ⫾ 2)†§
3.07 ⫾ 0.10
(77 ⫾ 3)†§
3.75 ⫾ 0.11
(98 ⫾ 2)
3.08 ⫾ 0.12
(79 ⫾ 2)†
3.03 ⫾ 0.10
(77 ⫾ 2)†
2.91 ⫾ 0.08
(73 ⫾ 2)†§
2.85 ⫾ 0.10
(73 ⫾ 2)†§
3.57 ⫾ 0.11
(93 ⫾ 2)
2.31 ⫾ 0.09
(75 ⫾ 2)†
2.28 ⫾ 0.09
(74 ⫾ 2)†
2.02 ⫾ 0.07
(65 ⫾ 2)†§
1.98 ⫾ 0.09
(68 ⫾ 3)†§
2.72 ⫾ 0.08
(90 ⫾ 2)
FEV1/FVC, %
RV/TLC, %
75 ⫾ 1
40 ⫾ 1
75 ⫾ 1
41 ⫾ 1
69 ⫾ 2†§
45 ⫾ 2†§
69 ⫾ 2†§
46 ⫾ 2†§
77 ⫾ 1
40 ⫾ 1
*Data are presented as mean ⫾ SE. See Table 1 for group definitions. Predicted values for TLC from Miller et al52; FVC, VC, and FEV, from
Knudson et al53; RV from Crapo et al.54
†Heart failure patients (groups 1 to 4) different from control subjects (group 5) (p ⬍ 0.05).
‡Heart failure, nonsmokers with CABG (group 2) different from heart failure, nonsmokers, no CABG (group 1) (p ⬍ 0.05).
§Heart failure, smokers (groups 3 and 4) different from heart failure, nonsmokers, no CABG (group 1) (p ⬍ 0.05).
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Table 3—Expiratory Flows*
Groups
1
2
3
4
5
PEF, L/s
(% Predicted)
FEF25, L/s
(% Predicted)
FEF50, L/s
(% Predicted)
FEF75, L/s
(% Predicted)
FEF25–75, L/s
(% Predicted)
MVV, L/min
(% Predicted)
7.56 ⫾ 0.31
(94 ⫾ 1)
7.86 ⫾ 0.31
(96 ⫾ 2)
7.28 ⫾ 0.31
(89 ⫾ 2)†
7.06 ⫾ 0.31
(89 ⫾ 2)†
7.73 ⫾ 0.30
(97 ⫾ 1)
5.41 ⫾ 0.22
(82 ⫾ 3)†
5.74 ⫾ 0.35
(82 ⫾ 4)†
4.86 ⫾ 0.31
(67 ⫾ 4)†‡
4.72 ⫾ 0.28
(70 ⫾ 4)†‡
5.78 ⫾ 0.22
(94 ⫾ 3)
2.51 ⫾ 0.15
(68 ⫾ 4)†
2.67 ⫾ 0.20
(71 ⫾ 4)†
1.97 ⫾ 0.14
(53 ⫾ 4)†‡
2.05 ⫾ 0.45
(56 ⫾ 4)†‡
2.98 ⫾ 0.13
(87 ⫾ 4)
0.72 ⫾ 0.06
(58 ⫾ 4)†
0.74 ⫾ 0.06
(57 ⫾ 3)†
0.50 ⫾ 0.03
(40 ⫾ 3)†‡
0.55 ⫾ 0.05
(49 ⫾ 5)†‡
0.85 ⫾ 0.05
(76 ⫾ 4)
1.95 ⫾ 0.12
(70 ⫾ 4)†
2.03 ⫾ 0.16
(70 ⫾ 4)†
1.42 ⫾ 0.09
(49 ⫾ 3)†‡
1.54 ⫾ 0.11
(57 ⫾ 4)†‡
2.25 ⫾ 0.10
(88 ⫾ 4)
89 ⫾ 4
(75 ⫾ 3)†
94 ⫾ 4
(77 ⫾ 2)†
87 ⫾ 4
(69 ⫾ 3)†
87 ⫾ 5
(74 ⫾ 3)†
103 ⫾ 4
(92 ⫾ 2)
*Data are presented as mean ⫾ SE. See Table 1 for group definitions. Predicted values for PEF, FEF25, FEF50, and FEF75, are from Knudson
et al.53
†Heart failure patients (groups 1 to 4) different from control subjects (group 5) (p ⬍ 0.05).
‡Heart failure, smokers (groups 3 and 4) different from heart failure, nonsmokers (groups 1 and 2) (p ⬍ 0.05).
Relationship of LV Size and Function to Lung
Volumes, Flow Rates, and DLCO
One hundred nineteen of a total of 203 patients
with LV dysfunction had echocardiographic results.
Weak correlations were observed among lung volumes, expiratory flows, Dlco, and several indexes of
cardiac function; however, no significant relationships were observed between lung function and
indexes of cardiac dimensions (p ⬎ 0.05). The most
significant relationships observed between the lung
volume measurements and cardiac function were the
association of TLC, FVC, and FEV1 (both absolute
values and percent predicted) with stroke volume (r2
range, 0.28 to 0.37, p ⬍ 0.01). We also noted weak
but significant correlations between right ventricular
pressures and cardiac index with percent-predicted
TLC and FVC (r2 range, 0.21 to 029, p ⬍ 0.05).
Dlco absolute values and predicted values were
weakly associated with stroke volume and ejection
fraction (r2 range, 0.22 to 0.26, p ⬍ 0.05). Although
no significant relationships were observed between
ejection fraction and lung volumes or expiratory
flows, when the subjects were split into the highest
and lowest ejection fractions (16 ⫾ 1 vs 29 ⫾ 1), the
group with the lowest LVEFs demonstrated slightly
lower lung volumes (percent-predicted TLC, FVC,
and FEV1), as well as a lower percent-predicted
Dlco (p ⬍ 0.05).
Discussion
We were interested in the changes in baseline
pulmonary function induced by stable chronic heart
Figure 1. Mean expiratory flow-volume curve of patients with
chronic heart failure alone (no history of smoking or CABG)
relative to control subjects and predicted values. CHF ⫽ chronic
heart failure; CTLS ⫽ control subjects; NS ⫽ nonsmoker;
NC ⫽ no previous CABG; PRED ⫽ predicted
Figure 2. Mean expiratory flow-volume curve of patients with
chronic heart failure and previous CABG relative to chronic heart
failure alone and predicted values. C ⫽ previous CABG; see
Figure 1 for definitions of abbreviations.
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Clinical Investigations
lung volume, expiratory flows were also reduced in
the subjects with chronic heart failure alone, particularly at the lower lung volumes (FEF50 and FEF75);
however, clear obstructive changes were most obvious in patients with a smoking history. Smoking
history or previous CABG also resulted in lower
Dlco values relative to patients with chronic heart
failure and no previous smoking or CABG history.
Previous Studies
Figure 3. Mean expiratory flow-volume curve of patients with
chronic heart failure and a smoking history compared to chronic
heart failure alone and predicted values; see Figures 1, 2 for
definitions of abbreviations.
failure independent of smoking history, history of
thoracic surgery, and morbid obesity. As summarized
in Figure 4, we found that patients with chronic
heart failure alone develop only mild restrictive
changes in PFT results relative to control subjects
and predictive values. Although these changes were
significant, in most routine clinical laboratories the
spirometric values would most likely be read as
mildly restrictive or within the normal range (ie,
within 2 SDs from the predicted values). Previous
thoracic surgery (primarily coronary artery bypass
surgery) tended to augment the observed restrictive
changes, particularly in nonsmokers. For a given
Table 4 —DLCO and VA*
Groups
1
2
3
4
5
Dlco, mL /min/mm Hg
(% Predicted)
22.3 ⫾ 0.7
(90 ⫾ 2)
19.1 ⫾ 0.6
(77 ⫾ 2)†‡
17.7 ⫾ 0.6
(72 ⫾ 3)†§
18.0 ⫾ 0.9
(74 ⫾ 3)†§
24.3 ⫾ 0.8
(102 ⫾ 2)
Va, L
5.23 ⫾ 0.15
5.06 ⫾ 0.14
5.04 ⫾ 0.13
5.12 ⫾ 0.16
5.46 ⫾ 0.16
*Data are presented as mean ⫾ SE. See Table 1 for group definitions. Predicted values are from Miller et al.52
†Heart failure patients (groups 1 to 4) different from control subjects
(group 5) (p ⬍ 0.05).
‡Heart failure, no CABG (groups 1 and 3) different from heart
failure, CABG (groups 2 and 4) (p ⬍ 0.05).
§Heart failure, smokers (groups 3 and 4) different from heart failure,
nonsmokers (groups 1 and 2) (p ⬍ 0.05).
Multiple studies6,7,9,14,25 have examined pulmonary function changes in patients with a history of
chronic heart failure; however, the majority of these
studies did not distinguish clearly smokers from
nonsmokers, a history of thoracic surgery, or significant obesity. In addition, the degree of stability or
relationship between acute exacerbations in chronic
heart failure symptoms has not always been clearly
distinguished. It is clear that as symptoms resolve
from an acute period of decompensation, pulmonary
function improves.10,26 VC has also been shown to
vary in conjunction with NaCl loading and unloading
over a 10-day period in patients with chronic heart
failure, demonstrating that acute changes in fluid
balance play a role in modulating pulmonary function changes.26 Most studies7,9,14 tend to show primarily restrictive rather than obstructive changes.
Obstructive changes tend to be mild and appear to
be more prevalent during periods of decompensation, and tend to improve with diuresis presumably
due to a reduction in extravascular lung water, and a
general reduction in pulmonary and bronchial blood
volumes.11,19,27 There may also be an enhanced
degree of airway reactivity that diminishes with
diuresis.28 The response to methacholine has been
shown to increase in patients with chronic heart
failure and control subjects with fluid loading.27
Small improvements in expiratory flows are observed
with anticholinergic and ␤-agonist drugs in patients
with chronic heart failure.9,29
In patients in more stable condition, the degree of
obstruction has been variable, but may relate to
adequacy of treatment and smoking history as suggested by our findings.11 Variability in obstructive
changes noted in the literature may also be due to
the evolution of therapy with the current widespread
use of ACE inhibitors vs past treatment. There also
is a large degree of variability related to “aging” alone
on pulmonary function and the observed obstructive
changes.30
Obesity is increasing at a rapid rate in the United
States and may contribute to some of the restrictive
changes observed in other studies of patients with
chronic heart failure.31 While the BMI was above
ideal in our study, we were careful to exclude
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Figure 4. Summary of pulmonary changes related to chronic heart failure, smoking history, and
previous CABG. Values are expressed relative to age-, gender-, and height-matched predicted values
(see Tables 2– 4 for predicted references).
subjects with clear morbid obesity from the comparisons (BMI ⬎ 35 kg/m2). In most studies31–33 examining obesity, the fall in TLC and VC is similar to that
observed in our patients with chronic heart failure
alone. This is presumably due to the enhanced
weight around the chest wall and abdomen and the
resultant increased respiratory muscle load.
Physiologic Mechanisms
The cause of the restrictive changes in chronic
heart failure remains unclear.1,2 We and others34 –36
have found lung compliance to be reduced in patients with chronic heart failure in stable condition,
consistent with the restrictive changes. Work by
Hosenpud et al7 and Niset et al37 suggests that some
of these changes (particularly the reduced VC) may
be related to cardiac size. Since the heart and lung
compete for space within the chest wall, an enlargement in cardiac size clearly could reduce VC and
TLC. Enright et al38 found a relationship between
LV posterior wall thickness in diastole and FVC in
the Cardiovascular Health Study; however, the relationship was weak (regression coefficient ⫽ ⫺ 0.246),
and FVC only appeared to decline significantly in
patients with the largest changes in LV size (ie, highest
deciles). Although we did not have cardiac dimensions
in all of our subjects, in those that were available (119
of 203 subjects; 59% of patients with chronic heart
failure), we found no relationships between these echo-
cardiographic measurements and our measurements of
lung function. Thus, within a group of patients with an
ejection fraction ⬍ 35%, cardiac dimensions based on
echocardiography do not appear to play a major role in
the lung volume changes. A more accurate assessment
may be to determine cardiac dimensions relative to
chest wall size. Since chest wall size varies significantly
for a given height and weight and general body habitus,
cardiac dimensions alone would not necessarily predict
alterations in lung function.
Since some of the restrictive changes observed in
chronic heart failure resolve with fluid unloading, it
has also been proposed that either an increase in
pulmonary and/or bronchial blood volume or an
increase in interstitial fluid accumulation likely accounts for some of these changes, even in patients
with stable chronic heart failure.7,39,40 General muscle weakness and wasting, including the respiratory
muscles, has also been well established in patients
with chronic heart failure.41– 43 Similar to our findings, several studies1,2,44 have noted a reduced MVV
in patients with chronic heart failure, likely related to
this muscle weakness. This may result in a reduced
ability to fully inspire, resulting in a reduced TLC
and a reduced FVC. In addition, it has been proposed that chronic heart failure is associated with
increased levels of circulating cytokines (such as
tumor necrosis factor-␣), which may induce changes
in lung parenchyma, or that high left atrial pressures
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Clinical Investigations
may induce chronic remodeling of the pulmonary
vasculature (smooth-muscle proliferation, intimal
and medial thickening, and fibrinoid necrosis and
arteritis) that could alter lung compliance and induce
the observed mild restrictive changes.1,2,4,43
Although we found an essentially normal resting
Dlco in our group with chronic heart failure alone,
most studies6,20,22,45 on patients with chronic heart
failure have found Dlco to be reduced. Our data
would suggest that patients with chronic heart failure
and a smoking history clearly demonstrate a reduction in Dlco, and previous CABG may also contribute to a reduction. The fall in Dlco in our smokers
is consistent with a loss of alveolar-capillary surface
area commonly described.46 The mechanism for the
reduced Dlco in postsurgical patients is unclear.
Previous studies47,48 have reported declines in Dlco
after cardiac surgery acutely that may persist for at
least 2 weeks; however, most of our patients were
many years postsurgery. Although speculative, this
may reflect pathophysiologic changes in the pulmonary microcirculation initiated by cardiopulmonary
bypass, as off-pump surgery eliminates potentially
negative consequences of cardiopulmonary bypass,
such as a systemic inflammatory response with coagulopathy and altered microvascular permeability.49
The disparity in Dlco in our patients with chronic
heart failure alone vs previous studies may also be
related to the more recent use of ACE inhibitors as
standard therapy in patients with chronic heart
failure. Work by Guazzi et al50 suggested that treatment with enalapril increased Dlco toward normal
in patients with LV dysfunction. Some recent data51
in our laboratory support the work of Guazzi et al,50
as patients with chronic heart failure homozygous for
the ACE deletion allele genotype (highest plasma
ACE levels) tended to have lower Dlco values than
those with the II genotype. This would suggest that
the derangement in neurohumoral function that
occurs with chronic heart failure might significantly
alter normal function of the alveolar-capillary membrane.
Potential Impact
Do the changes in baseline spirometry contribute
to the exertional dyspnea observed in this patient
group? Although the changes in lung volumes and
expiratory airflow are small, these changes may
impact the sensation of dyspnea in these patients.
We previously demonstrated that patients with
chronic heart failure tend to breathe at low lung
volumes at rest and during activity.44 The reduced
expiratory flow, particularly at these low lung volumes, reduces the breathing reserve and appears to
contribute to expiratory flow limitation. We also
found that it was difficult to increase end-expiratory
lung volume during exercise, despite apparent room
to do so, suggesting that the reduced lung and
possibly chest wall compliance may reduce the ability to avoid expiratory flow limitation (by increasing
end-expiratory lung volume), and this may contribute to an increased work of breathing and to an
enhanced sensation of dyspnea.
ACKNOWLEDGMENT: The authors thank Becky HughesBorst and Sue Nelson, LPN, for help in data collection, and
Audrey Schroeder for help with manuscript preparation.
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Clinical Investigations