Chronic Respiratory Disease 2009; 6: 177185

http://crd.sagepub.com

REVIEW SERIES: HEART AND LUNG DISEASE

Cor pulmonale
E Weitzenblum1 and A Chaouat2
1University

Hospital, Strasbourg, France; and 2University Hospital, Nancy, France

The term cor pulmonale is still popular but there is presently no consensual definition and it
seems more appropriate to define the condition by the presence of pulmonary hypertension
(PH) resulting from diseases affecting the structure and/or the function of the lungs: PH results
in right ventricular enlargement and may lead with time to right heart failure (RHF). Chronic
obstructive pulmonary disease (COPD) is the first cause of cor pulmonale, far before idiopathic
pulmonary fibrosis and obesityhypoventilation syndrome. In chronic respiratory disease
(CRD) PH is pre-capillary, due to an increase of pulmonary vascular resistance (PVR).
The first cause of increased PVR is chronic long-standing alveolar hypoxia which induces pulmonary vascular remodeling. The main characteristic of PH in CRD and particularly in COPD
is its mild to moderate degree, resting pulmonary artery mean pressure (PAP) in a stable state of
the disease usually ranging between 20 and 35 mmHg. However, PH may worsen during exercise, sleep, and exacerbations of the disease. These acute increases in afterload can favor the
development of RHF. A minority (<5%) of COPD patients exhibit severe or disproportionate PH (PAP >40 mmHg), the mechanism of which is not well understood. At present longterm oxygen therapy (LTOT) is the logical treatment of PH since alveolar hypoxia is considered
to be the major determinant of the elevation of PAP and PVR. LTOT stabilizes or at least
attenuates and sometimes reverses the progression of PH, but PAP seldom returns to normal.
Vasodilators (prostacyclin, endothelin receptor antagonists, sildenafil, nitric oxide) could be
considered in patients with severe PH but controlled studies in this field are presently lacking. Chronic Respiratory Disease 2009; 6: 177185
Key words: chronic respiratory failure; COPD; cor pulmonale; pulmonary hypertension

The term cor pulmonale is still popular in the medical literature, but there is presently no consensual
definition. In 1963, an expert committee of the
World Health Organization defined cor pulmonale
as hypertrophy of the right ventricle resulting from
diseases affecting the function and/or structure of the
lungs,1 but this pathological definition is in fact of
limited value in clinical practice. As pulmonary
hypertension (PH) is the sine qua non of cor pulmonale,2 we believe that the best definition of cor
pulmonale is the following: PH resulting from diseases affecting the structure and/or the function of
the lungs; PH results in right ventricular enlargement
and may lead with time to right heart failure (RHF).
This article reviews the current state of knowledge about PH resulting from disorders of the respiratory system and/or from chronic hypoxemia.
Particular emphasis will be placed on chronic
Correspondence to: E Weitzenblum (Professor), Service de Pneumologie, Nouvel Hpital Civil, 67091 Strasbourg Cedex, France.
Email: emmanuel.weitzenblum@chru-strasbourg.fr
The Author(s), 2009.
Reprints and permissions: http://www.sagepub.co.uk/journalsPermissions.nav

obstructive pulmonary disease (COPD), which is

by far the first cause of cor pulmonale.

Definition
In the new diagnostic classification of PH,3 cor
pulmonale corresponds to the third group of the
classification (PH associated with disorders of the
respiratory system and/or hypoxemia) and must be
distinguished from idiopathic pulmonary arterial
hypertension (IPAH) and neighboring conditions
(group 1), from pulmonary venous hypertension
(group 2) and from thromboembolic PH (group 4).
PH complicating chronic respiratory disease, particularly COPD, was generally defined by the presence of a pulmonary artery mean pressure (PAP)
> 20 mmHg, which is slightly different from the
definition of IPAH (PAP > 25 mmHg).4 In young,
healthy subjects, PAP is most often between 10 and
15 mmHg.5 With aging, there is a slight increase in
PAP, not exceeding 1 mmHg/10 years as a mean.5
10.1177/1479972309104664

Cor pulmonale
E Weitzenblum and A Chaouat

178

A resting PAP > 20 mmHg is always abnormal,

even in elderly subjects. In the natural history of
COPD, PH is often preceded by an abnormally
large increase in PAP during exercise,6 defined by a
pressure > 30 mmHg for a mild level of steady-state
exercise. The term exercising PH has been used, but
the term PH should be reserved for resting PH.

Epidemiology. Magnitude of the problem

Cor pulmonale is a common type of heart disease as
a result of its close association with COPD, which
has emerged, in recent years, as a leading cause of
disability and death.7 But there are few data about
the incidence and prevalence of cor pulmonale. The
main reason is that right heart catheterization
(RHC) cannot be performed on a large scale in
patients at risk. An alternative is the use of noninvasive methods, particularly Doppler echocardiography, which is presently the best method.8
From a study performed in the United Kingdom in
1985,9 it could be extrapolated that in England and
Wales ~60,000 subjects were at risk of PH because
they had both an FEV1 < 50% and a PaO2
< 55 mmHg. These data were obtained more than
20 years ago, and taking into account the marked
increase of prevalence in COPD in recent years,
these estimates should be increased by at least 100%.
The mortality related to cor pulmonale is difficult
to assess. There are data about the mortality resulting
from chronic lung disease (100,000/year in the United
States), but we do not know the role of secondary PH
in this mortality. PH is a complication, among
others, of advanced COPD, and it is impossible to
separate it accurately from respiratory failure.

Etiology: which chronic lung disease may

lead to cor pulmonale?
The third group of the new classification of PH3
includes COPD, interstitial lung disease, sleep disordered breathing, and alveolar hypoventilation
disorders. Table 1 lists more precisely the chronic
respiratory diseases that may lead to cor pulmonale.
There are three major groups of diseases:
 Those characterized by a limitation to airflow
(COPD and other causes of chronic bronchial
obstruction).
Chronic Respiratory Disease

Table 1 Diseases of the respiratory system associated with

pulmonary hypertension
Obstructive lung diseases
COPDa (chronic obstructive bronchitis, emphysema and their
association)
Asthma (with irreversible airway obstruction)
Cystic, fibrosisb
Bronchiectasis
Bronchiolitis obliterans
Restrictive lung diseases
Neuromuscular diseases
Kyphoscoliosisb
Sequelae of pulmonary tuberculosis
Sarcodosisb
Pneumoconiosis
Drug related lung diseases
Extrinsic allergic alveolitis
Connective tissue diseases
Idiopathic interstitial pulmonary fibrosisb
Interstitial pulmonary fibrosis of known origin
Combined pulmonary fibrosis and emphysemab
Respiratory insufficiency of central origin
Central alveolar hypoventilation
Obesity-hypoventilation syndromeb (formerly Pickwickian
syndrome)
Sleep apnea syndromeb
aVery

frequent cause of pulmonary hypertension.

frequent cause of pulmonary hypertension.
COPD, chronic obstructive pulmonary disease.

bRelatively

 Those characterized by a restriction of pulmonary volumes from extrinsic or parenchymatous

origin (restrictive lung diseases).
 Those where the relatively well-preserved mechanical properties of the lungs and chest wall contrast
with pronounced gas exchange abnormalities,
which are partially explained by poor ventilatory
drive (respiratory insufficiency of central origin).
COPD is the major cause of both chronic respiratory insufficiency and cor pulmonale and it probably
accounts for 80% of the cases. Among the restrictive
lung diseases, idiopathic pulmonary fibrosis is a
frequent cause of PH.10 Among the etiologies of respiratory insufficiency of central origin, the obesityhypoventilation syndrome (formerly Pickwickian
Syndrome) is a relatively frequent cause of PH.11
The combination of pulmonary fibrosis (lower
lobes) and emphysema (upper lobes) has recently
been described as a distinct underrecognized
entity.12 This rare disease is a cause of PH.

Pathophysiology: mechanisms of PH
in chronic respiratory disease
As stated above, PH is the sine qua non of cor
pulmonale. Accordingly, the mechanisms of cor

Cor pulmonale
E Weitzenblum and A Chaouat

179

pulmonale are first those of PH. In chronic respiratory diseases, PH results from increased pulmonary
vascular resistance (PVR), whereas cardiac output
and pulmonary capillary wedge pressure
(PCWP) are generally normal; PH is said to be
precapillary.
The factors leading to an increased PVR in chronic
respiratory diseases are listed in Table 2. These factors are numerous,13,14 but alveolar hypoxia is by
far the predominant one,2,13,15 at least in COPD,
kyphoscoliosis, and the obesity-hypoventilation
syndrome.16 In interstitial lung diseases, the elevated
PVR is due to a variable combination of anatomical
(tissue destruction and loss of pulmonary vascular
bed consecutive to lung fibrosis17) and physiological
factors (alveolar hypoxia17,18).
Two distinct mechanisms of action of alveolar
hypoxia must be considered: acute hypoxia causes
pulmonary vasoconstriction and chronic hypoxia
induces with time structural changes in the pulmonary vascular bed, the so-called remodeling of the
pulmonary vasculature.
Acute alveolar hypoxia induces in humans and
in almost all species of mammals a rise of PVR
and PAP, which is accounted for by hypoxic pulmonary vasoconstriction. Hypoxic vasoconstriction is
observed in normal subjects as well as in patients
with chronic respiratory disease.19 This vasoconstriction is localized in small precapillary arteries,
and its mechanism is now better understood.20 In
fact, the reactivity of the pulmonary circulation to
acute hypoxia varies from one individual to another
and this interindividual variability is also found in
COPD patients.21
Chronic alveolar hypoxia induces in healthy people living at altitudes > 3500 m precapillary PH,
nearly identical to that observed in COPD,22 and
Table 2 Factors increasing pulmonary vascular resistance in
chronic respiratory diseases
Anatomic factors: reduction (destruction, obstruction) of the
pulmonary vascular bed
Thromboembolic lesions
Fibrosis
Emphysema
Functional factors
Alvolar hypoxiaa
Acute hypoxia (pulmonary vasoconstriction)
Chronic hypoxia (remodeling of the pulmonary vascular bed)
Acidosis, hypercapnia
Hyperviscosity (polycythemia)
Hypervolemia (polycythemia)
Mechanical factors (compression of alveolar vessels)
aMost

important factor.

morphological studies have shown remodeling of

the pulmonary vascular bed, somewhat similar to
the structural changes observed in COPD patients
with PH (muscularization of pulmonary arterioles,
intimal thickening in muscular pulmonary arteries
and arterioles).
It is accepted that remodeling of the pulmonary
vasculature induced by chronic alveolar hypoxia is
the major cause of elevated PVR and PAP in
COPD, but it should be remembered that chronic
alveolar hypoxia is not the only cause of an elevated
PVR: these patients have marked morphological
changes of the lung parenchyma, particularly when
emphysema is severe and these changes, including
the loss of pulmonary capillaries, could partly
account for the increased PVR.23
Finally, it has been known for many years that
pulmonary vascular remodeling is present not only
in end-stage COPD patients but also in patients with
mild COPD.24 It has been shown more recently that
smokers with normal lung function may develop
intimal thickening in pulmonary muscular arteries,
possibly a consequence of endothelial dysfunction
caused by cigarette smoke,25 but the clinical relevance of these early abnormalities is presently
unknown.

Diagnosis of cor pulmonale

Symptoms and physical signs are of little help in the
diagnosis of cor pulmonale. Dyspnea on exertion
and fatigue is generally present in advanced chronic
respiratory disease with or without PH. In COPD,
they are essentially the consequence of airflow limitation and hyperinflation rather than PH. Physical
signs that are observed in severe PH and particularly
in IPAH [e.g., pansystolic murmur owing to tricuspid regurgitation (TR)] are rarely present in respiratory patients with PH. This can be explained by the
modest degree of PH in most patients and by the late
occurrence (or no occurrence at all) of RHF. Peripheral edema occurs rather late in the course of chronic
respiratory disease, particularly COPD, and is not
synonymous with RHF.26,27
The sensitivity of electrocardiogram for the diagnosis of PH is poor (2040%), whereas the specificity
of signs of right ventricular hypertrophy is high.28
The radiologic prediction of PH is even more problematic, since the radiologic signs lack both sensitivity and specificity.28 Magnetic resonance imaging
may prove useful for the diagnosis of PH and altered
right ventricular structure and function. It produces
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Cor pulmonale
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180

excellent images of the right ventricle, but it is not

routinely used in respiratory patients suspected of
exhibiting PH.
The non-invasive diagnosis of PH is presently
based on Doppler echocardiography, which is by
far the best method.8 The maximum velocity of the
TR jet allows the calculation of the right ventricle
right atrial pressure gradient by applying the Bernoulli equation. The calculated gradient is added
to the (estimated) right atrial pressure to give an
estimated value of right ventricular systolic pressure
that is equal to the pulmonary artery systolic pressure. With the same technique, in case of pulmonary
regurgitation, it is possible to estimate the pulmonary artery diastolic pressure. In COPD patients,
hyperinflation makes echocardiography difficult
and a reliable examination cannot be obtained in
more than 6080% of the cases.29 The good correlation observed in cardiac patients between PAP estimated from echo data and PAP measured invasively
has not always been confirmed in COPD patients
and a mean error of estimate for systolic PAP of
about 10 mmHg has been reported.29 In a large
series (n = 374) of patients candidates for lung transplantation, most of them exhibiting COPD, the
estimation of systolic PAP by Doppler echocardiography was possible in only 44% of the patients and
52% of pressure estimations were found to be inaccurate (>10 mmHg difference compared with pressure measured invasively).30
In spite of technical difficulty in COPD patients,
Doppler echocardiography remains the best noninvasive method for the diagnosis of PH and it
may complement RHC when the latter is mandatory by providing additional information.8
Plasma brain natriuretic peptide (BNP) release is
due to increased wall stretch of atria and ventricles
and may have a relatively good sensitivity for the
assessment of PH in chronic respiratory disease.31
However, further studies are needed to determine
whether BNP is a useful diagnostic tool in respiratory patients.
RHC continues to be the gold standard for the
diagnosis of PH.13,14 It allows the direct measurement of PAP, PCWP, right heart filling pressures
and cardiac output (by thermodilution or according
to the Fick principle), and the calculation of PVR
(PAP PCWP/Q, where Q is cardiac output). Measurements can be obtained during steady-state
exercise and after therapeutic intervention. But
RHC is an invasive procedure, which has some
risks and cannot be routinely performed in respiratory patients.
Chronic Respiratory Disease

In patients with chronic respiratory disease,

Doppler echocardiography must be attempted
when PH is suspected. The indications for RHC
should be limited to the cases when a severe PH is
suspected (systolic pressure estimated from Doppler
echocardiography >5060 mmHg).

Hemodynamic features: characteristics of

PH in chronic respiratory disease
PH in chronic respiratory disease is precapillary,
with an increased pressure difference between PAP
and PCWP reflecting the increased PVR. The main
characteristic of PH in chronic respiratory disease,
and particularly in COPD, is probably its mild to
moderate degree, resting PAP in a stable state of
the disease ranging usually between 20 and
35 mmHg.32,33 This modest degree of PAP,
observed in COPD and also in obesityhypoventilation syndrome11 and idiopathic pulmonary fibrosis,10 is very different from other causes of
PH such as pulmonary thromboembolic disease,
and in particular IPAH in which PAP is usually
>40 mmHg and may exceed 80 mmHg in some
patients. Table 3 compares the pulmonary hemodynamic data of COPD patients and other causes of
chronic respiratory disease with large series of
IPAH34 and thromboembolic PH35: it can be seen
that the average PAP is markedly elevated in IPAH
(56 mmHg) and in thromboembolic PH (46 mmHg)
but modestly increased in COPD (26 6 mmHg).
A PAP > 40 mmHg is thus unusual in COPD except
when the patients are investigated during an acute
exacerbation or when there is an associated cardiopulmonary disease.33 The consequences of the (generally) modest degree of PH in chronic respiratory
disease include the absence or late occurrence of
RHF. However, PH, even mild at baseline, may
worsen during exercise, sleep, and acute exacerbations of the disease.
During steady-state exercise, PAP increases
markedly in advanced COPD patients with resting
PH. COPD patients whose baseline PAP is mildly
elevated (2530 mmHg) may exhibit severe PH (50
60 mmHg) during moderate (3040 W) exercise.
This is explained by the fact that PVR does not
decrease during exercise in these advanced
patients,36,37 whereas it does in healthy subjects.
This means that daily activities such as climbing
stairs or even walking can induce profound PH.38
Acute increases of PAP during sleep have been
observed in COPD patients with respiratory failure

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181

Table 3 Comparison of pulmonary hypertension in chronic hypoxic lung disease (COPD, IPF, OHS) to idiopathic PAH and
CTEPH

References
Number of patients
Age
FEV1 (mL)
FEV1 (% of predicted)
PaO2 (mmHg)
PaCO2 (mmHg)
PAP (mmHg)
PCWP (mmHg)
Q (L/min/m)

COPD

IPF

OHS

Idiopathic PAH

CTEPH

Weitzenblum, et al.32
62
55 8
1170 390

60 9
45 6
26 6
82
3.8 1.1

Weitzenblum, et al.18
31
58 16
1655 650

68 12
35 5
24 11
74
3.4 0.8

Kessler, et al.11
36
62 12
1610 600

59 8
50 4
26 10

2.9 0.9

Humbert, et al.34
259
50

>70

56
8
2.3

Jamieson, et al.35
500

46

2.2

Mean values standard deviation.

COPD, chronic obstructive pulmonary disease; IPF, idiopathic pulmonary fibrosis; OHS, obesity-hypoventilation syndrome; PAH, pulmonary
arterial hypertension; CTEPH, Chronic thromboembolic pulmonary hypertension; FEV1, forced expiratory volume in 1 s; PAP, pulmonary artery
mean pressure; PCWP, pulmonary capillary wedge pressure; Q, cardiac output.

exhibiting daytime hypoxemia and PH.39,40 They

are principally observed in rapid eye movement
sleep during which dips in oxygen saturation are
more severe. These episodes of sleep-related
desaturation are not due to apneas but to alveolar
hypoventilation
and/or
ventilation-perfusion
mismatching.40,41 PAP can increase by as much as
20 mmHg from its baseline value.39 These acute
increases of PAP reflect hypoxic pulmonary
vasoconstriction.
Severe exacerbations of chronic respiratory disease, occurring in patients with chronic respiratory
failure, are characterized by a worsening of hypoxemia and hypercapnia and simultaneously there is
a pronounced increase in PAP.42 PAP can increase
by 20 mmHg but usually returns to baseline after
recovery.43 There is a parallel between the changes
in PaO2 and PAP, suggesting the presence of hypoxic pulmonary vasoconstriction.
The acute increases of afterload occurring during
exercise, sleep, and particularly during exacerbations
of the disease can favor the development of RHF.44

Severe or disproportionate PH
in chronic respiratory disease
The concept of disproportionate PH is recent and
relates to COPD patients33,45 but can be extended to
other causes of chronic respiratory disease. We have
seen that in COPD, PH is usually mild to moderate.
A minority of patients exhibit severe PH, which can
be defined by a resting PAP > 3540 mmHg. This
level of PH is considered as disproportionate
and recent studies aimed to evaluate its frequency
and understand its mechanisms.

Chaouat, et al.33 have observed that out of

998 patients, undergoing RHC during a period
of disease stability, only 27 had a resting
PAP > 40 mmHg. Of these 27 patients, 16 had
an associated disease possibly causing PH (e.g.,
severe obesity plus obstructive sleep apneas). Only
11 patients (1.1%) had COPD as the only cause of
PH. Table 4 compares these patients with COPD
patients with usual PH and COPD patients without PH, and it can be observed that patients with
severe PH have less severe bronchial obstruction
than the remainder; they have profound hypoxemia,
hypocapnia, and a marked decrease of diffusion
capacity for CO. Thabut, et al.45 have identified a
very similar subgroup of COPD patients (16/215
severe COPD patients), in whom pulmonary vascular disease is predominant.
The presence of severe PH in some COPD
patients who may exhibit moderate airflow obstruction (but have severe hypoxemia) could be explained
by the fortuitous coexistence of COPD and a pulmonary vascular disease somewhat similar to IPAH.33
It is necessary to detect these COPD (or more
generally, chronic respiratory disease) patients with
severe PH because they have a very poor prognosis
when compared with other COPD patients, in spite
of oxygen therapy.33 These patients should be
referred to an expert center of pulmonary vascular
disease and should be included in registries and
clinical trials.14

From PH to RHF
The progression of PH is slow, at least in
COPD.43,46,47 To our knowledge, similar studies
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182

Table 4 Comparison of three groups of patients with chronic obstructive pulmonary disease classified according to the presence
and severity of pulmonary hypertension

Age (years)
FEV1 (% predicted)
FEV1/VC (%)
DLCO (mL/min/mmHg)
PaO2 (mmHg)
PaCO2 (mmHg)
A-aO2 (mmHg)
PAP (mmHg)
PCWP (mmHg)
Q (L/min/m)
TPR (IU/m)

Group 1

Group 2

Group 3

Severe PH without associated

disease (n = 11)

Control group (PAP > 20 mmHg)

(n = 16)

Control group (PAP < 20 mmHg)

(n = 16)

67
50
49
4.6
46
32
56
48
6
2.3
21.3

66
27
34
10.3
56
47
30
25
7
2.8
9.0

62
35
39
13
72
40
28
16
7.5
3.3
4.0

(6268)
(4456)
(3953)
(4.26.7)
(4153)
(2837)
(5068)
(4650)
(47)
(1.82.5)
(17.636.6)

(6373)
(2334)
(2638)
(8.912.8)
(5464)
(4449)
(2737)
(2237)
(6.57.5)
(2.43.1)
(7.49.9)

(5375)
(2950)
(3152)
(11.017.0)
(6876)
(3742)
(2534)
(1318)
(77.5)
(2.94.0)
(3.75.5)

Values are median (interquartile range).

Severe PH (group 1) is defined by PAP > 40 mmHg. In group 2, PAP ranges between 20 and 40 mmHg (usual PH). In group 3, PAP
is <20 mmHg (no PH).
Group 1 is characterized by less severe bronchial obstruction, marked decrease of DLCO, profound hypoxemia, and marked hypocapnia; the
differences are statistically significant with the two other subgroups.
PH, pulmonary hypertension; PAP, pulmonary artery mean pressure; FEV1, forced expiratory volume in 1 s; VC, vital capacity; DLCO, diffusion
capacity for carbon monoxide; PaO2, partial pressure of arterial oxygen; PaCO2, partial pressure of arterial carbon dioxide; A-aO2, alveolararterial PO2 difference; PCWP, pulmonary capillary wedge pressure; Q , cardiac output; TPR, total pulmonary resistance;
Adapted from Chaouat, et al.33

are not available for idiopathic pulmonary fibrosis,

sleep apnea syndrome, and obesity-hypoventilation
syndrome. In COPD, PAP may remain stable over
periods of 312 years.43,46,47 In a study47 in which
93 patients were followed up during a mean of
90 months, the average change in PAP was only
+0.5 mmHg/year for the group as a whole. The evolution of PAP was identical in patients with and
without initial PH (defined by PAP > 20 mmHg).
A further study on the natural history of PH in
COPD patients with an initial PAP < 20 mmHg
showed that only 33/121 developed PH after a
mean interval of 6.8 2.9 years.6 Nevertheless, a
minority (approximately 30%) of advanced COPD
patients exhibit a notable worsening of PAP during
the follow-up47: these patients do not differ from the
others at the onset, but they are characterized by a
progressive worsening of PaO2 and PaCO2 during
the evolution, and there is a significant correlation
between the changes in PaO2 and PAP.43,47 The longitudinal evolution of PH is favorably influenced by
long-term oxygen therapy (LTOT) (see below).
The classical view of the development of RHF in
patients with chronic respiratory disease is as follows: PH increases the work of the right ventricle,
which leads to right ventricular enlargement (hypertrophy plus dilatation), which can result in right
ventricular dysfunction. Later, RHF, characterized
by the presence of peripheral edema, can be
Chronic Respiratory Disease

observed in some COPD patients. There is a relationship between the severity of PH and the development of RHF.
Peripheral edema is frequently observed in
advanced COPD patients and is considered to
reflect RHF, but the possible occurrence of RHF
in these patients has been questioned,26,27 in particular because the degree of PH is most often mild in
COPD. Peripheral edema is not synonymous with
RHF13,27 and may simply indicate the presence
of secondary hyperaldosteronism induced by functional renal insufficiency.48
The role of pressure overload in the development
of RHF in these patients has also been debated.
MacNee, et al.49 comparing COPD patients with
and without clinical (edema) and hemodynamic
signs of RHF concluded that RHF was probably
due to other causes than PH. A study from our
group44 has led to different conclusions: in 9/16
patients with marked peripheral edema, hemodynamic signs of RHF were present and were
probably accounted for by a significant worsening
of PH during the episode of edema which in turn
was explained by a worsening of hypoxemia.
Right ventricular contractility, assessed by the
end-systolic pressurevolume relation, is near normal in COPD patients with PH investigated in a
stable state but has been found decreased during

Cor pulmonale
E Weitzenblum and A Chaouat

183

severe exacerbations with marked peripheral

oedema.49
Thus, many patients with advanced COPD will
never develop RHF, and on the other hand, at
least some patients experience episodes of true
RHF during exacerbations of the disease accompanied by a worsening of PH.44

Prognosis of cor pulmonale

The level of PAP is a good indicator of prognosis
in COPD32,50 and in other categories of chronic
respiratory disease, such as idiopathic pulmonary
fibrosis.50 The prognosis is worse in patients with
PH compared with patients without PH32 and is
particularly poor in patients with a severe degree of
PH.33,50
The five-year survival rate of COPD patients with
PH (PAP > 20 mmHg) is approximately 50%.32,50
LTOT significantly improves the survival of
markedly hypoxemic COPD patients, most of
them exhibiting PH.51,52 Accordingly, it can be
expected that the prognosis of PH will improve
with LTOT. PAP is still an excellent prognostic indicator in COPD patients treated with LTOT, which
can be explained by the fact that it is a good marker
of both the duration and the severity of alveolar
hypoxia in these patients.53

zation of PH under LTOT.55 However, PAP seldom

returns to normal. The best hemodynamic results
have been obtained in the studies in which the
daily duration of LTOT was the longest
(>18 h/day).51,54 Accordingly, one should recommend continuous oxygen therapy.
Treatment of IPAH has shown a dramatic change
in the past few years. Epoprostenol, prostacyclin
analogs, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors were tested in controlled
trials leading to the approval of several drugs. It is
tempting to use these drugs in PH complicating
respiratory diseases, particularly in the (rare) cases
of disproportionate PH. Unfortunately, there
have been very few studies in this field.
Nitric oxide (NO) is a selective and potent pulmonary vasodilator. One long-term study56 on 40
patients already on LTOT has shown that the addition of NO produced a significant improvement in
PAP, PVR, and cardiac output. However, the technological and toxicologic problems related to the
prolonged use of NO are far from being solved.
It is presently not recommended to treat respiratory (and particularly COPD) patients with vasodilator drugs dedicated to IPAH outside trials.
Randomized controlled studies are required in
this area.

References
Treatment of cor pulmonale
The treatment of RHF involves diuretics (most
often frusemide) and oxygen therapy. The treatment
of PH includes LTOT and vasodilators. Is it really
necessary to treat PH in chronic hypoxic lung disease? We have seen that PH, when present, is mild to
moderate in most COPD patients and the necessity
for treatment can be questioned. The best argument
in favor of treatment is that PH, even when modest
during a stable state of the disease, may worsen particularly during acute exacerbations, and these acute
increases in PAP can contribute to the development
of RHF.44
LTOT, which is prescribed to markedly hypoxemic (PaO2 < 55 mmHg) respiratory patients has
favorable pulmonary hemodynamic effects as
demonstrated by the pivotal NOTT and MRC
studies.51,52 Further studies more specifically
devoted to the pulmonary hemodynamic evolution
under LTOT54,55 have shown either a tendency to
the reversal of the progression of PH54 or a stabili-

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Dominighetti, G, et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol 2004; 43: 5S12S.
4. Fishman, AP. Clinical classification of pulmonary hypertension.
Clin Chest Med 2001; 22: 385391.
5. Tartulier, M, Bourret, M, Deyrieux, F. Les pressions artrielles
pulmonaires chez lhomme normal. Effets de lge et de lexercice
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