СHRONIC COR PULMONALE

Introduction
The term cor pulmonale was introduced in 1931 by Dr. Paul D.
White. In 1963, The World Health Organization expert
committee proposed a pathologic definition of cor pulmonale
as "hypertrophy of the right ventricle resulting from diseases
affecting the function and/or structure of the lungs, except
when these pulmonary alterations are the result of diseases
that primarily affect the left side of the heart, as in congenital
heart diseases." In 1970, Behnke and colleagues replaced the
concept of hypertrophy with "an alteration in the structure and
function of the right ventricle." This definition thus included a
variety of disorders ranging from a mild abnormality of the
right ventricle to overt right heart failure. The current
definition of chronic cor pulmonale is right ventricular
hypertrophy, dilation, or both as a result of pulmonary
hypertension caused by pulmonary disorders involving
the lung parenchyma, impaired pulmonary bellows
function, or altered ventilatory drive.
Right ventricular dilation or hypertrophy in
chronic cor pulmonale is a direct
compensatory effect of chronic pulmonary
vasoconstriction and subsequent pulmonary
artery hypertension that leads to increased
right ventricular work and stress. When the
right ventricle can no longer compensate
through dilation or hypertrophy, right
ventricular failure occurs.
A new diagnostic classification of pulmonary
hypertension was developed by a group of
experts in 1998
New diagnostic classification of pulmonary hypertension
1. Pulmonary arterial hypertension
1.1 Primary pulmonary hypertension
(a) Sporadic
(b) Familial
1.2 Related to:
(a) Collagen vascular disease
(b) Congenital systemic to pulmonary shunts
(c) Portal hypertension
(d) HIV infection
(e) Drugs/toxins
(1) Anorexigens
(2) Other
(f ) Persistent pulmonary hypertension of the newborn
(g) Other
2. Pulmonary venous hypertension
2.1 Left sided atrial or ventricular heart
disease
2.2 Left sided valvar heart disease
2.3 Extrinsic compression of central
pulmonary veins
(a) Fibrosing mediastinitis
(b) Adenopathy/tumours
2.4 Pulmonary veno-occlusive disease
2.5 Other
3. Pulmonary hypertension associated with
disorders of the respiratory system and/or
hypoxaemia
3.1 Chronic obstructive pulmonary disease
3.2 Interstitial lung disease
3.3 Sleep disordered breathing
3.4 Alveolar hypoventilation disorders
3.5 Chronic exposure to high altitude
3.6 Neonatal lung disease
3.7 Alveolar capillary dysplasia
3.8 Other
4. Pulmonary hypertension caused by
chronic thrombotic and/or embolic
disease
4.1 Thromboembolic obstruction of proximal
pulmonary arteries
4.2 Obstruction of distal pulmonary arteries
(a) Pulmonary embolism (thrombus,
tumour, ova and/or parasites, foreign
material)
(b) In situ thrombosis
(c) Sickle cell disease
5. Pulmonary hypertension caused by
disorders directly affecting the pulmonary
vasculature
5.1 Inflammatory
(a) Schistosomiasis
(b) Sarcoidosis
(c) Other
5.2 Pulmonary capillary haemangiomatosis
In our opinion cor pulmonale corresponds to
the third part of this classification (pulmonary
hypertension associated with disorders of the
respiratory system and/or hypoxaemia) and
must be differentiated from pulmonary
venous hypertension (part 2), and also from
primary pulmonary hypertension (part 1) and
from thromboembolic pulmonary
hypertension (part 4).
Aetiology
There are three major groups of diseases:
1. those characterised by a limitation to airflow.
Chronic obstructive pulmonary disease (COPD) and
other causes of chronic bronchial obstruction;
2. those characterised by a restriction of pulmonary
volumes from extrinsic or parenchymatous origin
(restrictive lung diseases);
3. 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).
 Diseases of the respiratory system associated with pulmonary hypertension (except primary
pulmonary hypertension, pulmonary thromboembolic disease, and diseases of the pulmonary
vascular bed)

Obstructive lung diseases

COPD (chronic obstructive bronchitis, emphysema and their association)
Asthma (with irreversible airway obstruction)
Cystic fibrosis
Bronchiectasis
Bronchiolitis obliterans
Restrictive lung diseases
Neuromuscular diseases: amyotrophic lateral sclerosis, myopathy, bilateral diaphragmatic paralysis,
etc
Kyphoscoliosis
Thoracoplasty
Sequelae of pulmonary tuberculosis
Sarcoidosis
Pneumoconiosis
Drug related lung diseases
Extrinsic allergic alveolitis
Connective tissue diseases
Idiopathic interstitial pulmonary fibrosis
Interstitial pulmonary fibrosis of known origin
Respiratory insufficiency of "central" origin
Central alveolar hypoventilation
Obesity–hypoventilation syndrome (formerly "Pickwickian syndrome")
Sleep apnoea syndrome
Chronic obstructive pulmonary disease is the major
cause of chronic respiratory insufficiency and cor
pulmonale, and it probably accounts for 80–90% of
the cases. Chronic obstructive pulmonary disease
includes chronic obstructive bronchitis and
emphysema, which are often associated. Among the
restrictive lung diseases kyphoscoliosis, idiopathic
pulmonary fibrosis, and pneumoconiosis are the
main causes of cor pulmonale. Among the
aetiologies of respiratory insufficiency of "central"
origin the obesity–hypoventilation syndrome
(formerly "Pickwickian syndrome") is a relatively
frequent cause of cor pulmonale.
Mechanisms of cor pulmonale
As stated above pulmonary hypertension is the necessary condition
of cor pulmonale. Accordingly, the mechanisms of cor pulmonale
are first those of pulmonary hypertension. In chronic respiratory
diseases pulmonary hypertension results from increased
pulmonary vascular resistance (PVR).
The factors leading to an increased pulmonary vascular resistance
in chronic respiratory disease are numerous but alveolar hypoxia
is by far the most predominant, at least in сhronic obstructive
pulmonary disease, kyphoscoliosis, and the obesity–
hypoventilation syndrome. Two distinct mechanisms of action of
alveolar hypoxia must be considered: acute hypoxia causes
pulmonary vasoconstriction, and chronic longstanding hypoxia
induces structural changes in the pulmonary vascular system
such as hypertrophy of the muscular media of the small
pulmonary arteries, muscularisation of pulmonary arterioles, and
intimal fibrosis. It is pulmonary vascular remodelling.
Furthermore, other functional factors must be
considered, namely hypercapnic acidosis and
hyperviscosity caused by polycythaemia, but
their role seems small when compared to that
of alveolar hypoxia. In pulmonary fibrosis the
increase of pulmonary vascular resistance is
caused by anatomical factors: loss of
pulmonary vascular bed or compression of
arterioles and capillaries by the fibrosing
process.
Pulmonary hypertension increases the work of the
right ventricle, which leads more or less rapidly to
right ventricular enlargement (associating
hypertrophy and dilatation), which can result in
ventricular dysfunction (systolic, diastolic). Later,
right heart failure (RHF) characterised by the
presence of peripheral oedema can be observed, at
least in some respiratory patients. The interval
between the onset of pulmonary hypertension and
the appearance of right heart failure is not known
and may vary from one patient to another. There is
a relation between the severity of pulmonary
hypertension and the development of right heart
failure.
Clinical signs
History
Clinical manifestations of cor pulmonale generally are nonspecific.
The symptoms may be subtle, especially in early stages of the
disease, and mistakenly may be attributed to the underlying
pulmonary pathology. The patient may complain of fatigue,
exertional dyspnea and syncope with exertion—symptoms
reflecting a relative inability to increase cardiac output during
exercise with a subsequent drop in the systemic arterial
pressure. Exertional chest pain also can occur and may be due
to pulmonary artery stretching and right ventricular ischemia.
Other symptoms mainly related to pulmonary artery hypertension
include cough and, sometimes, hemoptysis. In advanced
stages, passive hepatic congestion secondary to severe right
ventricular failure may lead to anorexia, right upper quadrant
abdominal discomfort, and jaundice. Swelling of the legs also
can occur, and syncope is a late and ominous occurrence.
Physical exam
The most evident physical findings in cor pulmonale reflect the
underlying lung disease, with an increase in chest diameter, labored
respiratory efforts with retractions of the chest wall, hyperresonance
to percussion, diminished breath sounds, wheezing, distant heart
sounds, and, rarely, cyanosis. Physical findings characteristic of
pulmonary hypertension, right ventricular hypertrophy (RVH) and
right ventricular failure also may be present.
 Early signs characteristic of pulmonary artery hypertension include
splitting of the second heart sound with accentuation of the
pulmonic component.
 Right ventricular hypertrophy is characterized by a left parasternal
or subxiphoid heave. A prominent a wave in the jugular venous
pulse associated with a right-sided fourth heart sound also can be
present and reflects the increase in the filling pressure of the right
ventricle.
 Right ventricular failure leads to systemic venous congestion, which
is manifested as distended neck veins, occasionally associated with
pulsatile liver, and peripheral edema. Pleural effusions and ascites
are uncommon, even in severe cor pulmonale.
Laboratory studies
Laboratory investigations are directed toward
defining the potential underlying etiologies as
well as evaluating complications of cor
pulmonale. In specific instances, appropriate
lab studies may include the following:
hematocrit for polycythemia, serum alpha1-
antitrypsin if deficiency is suspected, and
antinuclear antibody level for collagen
vascular disease. Hypercoagulability states
can be evaluated by serum levels of proteins
S and C, antithrombin and other tests
Imaging Studies
Chest roentgenogram: The chest x-ray in patients with
chronic cor pulmonale may show enlargement of the central
pulmonary arteries with oligemic peripheral lung fields.
Pulmonary hypertension should be suspected when the right
descending pulmonary artery is larger than 16 mm in diameter
and the left pulmonary artery is larger than 18 mm in
diameter.
 Right ventricular enlargement leads to an increase of the
transverse diameter of the heart shadow to the right on the
posteroanterior view and filling of the retrosternal air space
on the lateral view.
 These findings have reduced sensitivity in the presence of
kyphoscoliosis or hyperinflated lungs.
Echocardiography: Two-dimensional echocardiography
usually demonstrates signs of chronic right ventricular
pressure overload.
 As this overload progresses, increased thickness of the right
ventricular wall with paradoxical motion of the interventricular
septum during systole occurs.
 At an advanced stage, right ventricular dilatation occurs, and
the septum shows abnormal diastolic flattening. In extreme
cases, the septum actually may bulge into the left ventricular
cavity during diastole.
 Doppler echocardiography is used now to estimate pulmonary
arterial pressure, taking advantage of the functional tricuspid
insufficiency that usually is present in pulmonary
hypertension. Doppler echocardiography is considered the
most reliable noninvasive technique to estimate pulmonary
artery pressure. The efficacy of Doppler echocardiography
may be limited by the ability to identify an adequate tricuspid
regurgitant jet, which may be further enhanced by using saline
contrast.
In selected cases, ventilation-perfusion lung
scanning, pulmonary angiography, and
chest computer tomography scanning
may be indicated to determine underlying
etiology.
Other Tests:
Electrocardiography. Electrocardiogram abnormalities in cor
pulmonale reflect the presence of right ventricular hypertrophy or
strain.
 Electrocardiogram criteria for cor pulmonale such as right axis
deviation have high specificity but low sensitivity, particularly in
patients with biventricular hypertrophy.
 P-pulmonale pattern due to right atrial enlargement and right
bundle branch conduction abnormalities may be present.
 Patients with severe underlying obstructive lung disease may
have low-voltage QRS on their electrocardiogram, reflecting the
interposition of hyperexpanded lung between the heart and chest
wall.
 Additionally, many rhythm disturbances may be present in
chronic cor pulmonale.
 In selected cases, pulmonary function testing may be
indicated to determine underlying etiology.
Procedures:
 Cardiac catheterization: Right-heart catheterization
is considered the most precise method for diagnosis
and quantification of pulmonary hypertension. It is
indicated when echocardiography cannot assess the
severity a tricuspid regurgitant jet, thus excluding an
assessment of pulmonary hypertension. Right-heart
catheterization occasionally is important for
differentiating cor pulmonale from occult left
ventricular dysfunction, especially when the
presentation is confusing. Another indication may be
for evaluation of the potential reversibility of
pulmonary arterial hypertension with vasodilator
therapy.
 Lung biopsy occasionally may be indicated to
determine underlying etiology.
Differential diagnosis
Other problems to be considered:
 Congestive (biventricular) heart

failure
 Pulmonic valve stenosis

 Primary pulmonary hypertension

 Congestive heart failure
Congestive heart failure should be considered first of all.
Congestive heart failure is the pathophysiologic state in which the
heart, via an abnormality of cardiac function fails to pump blood
at a rate commensurate with the requirements of the
metabolizing tissues. Heart failure always causes circulatory
failure.
Heart failure may be caused by myocardial failure. Two thirds caused by
coronary artery disease. The second most common cause is dilated
cardiomyopathy. Other causes include chronic hypertension, valvular
heart disease, hypertrophic cardiomyopathy, and restrictive
cardiomyopathy.
Typical symptoms include fatigue, dyspnea, orthopnea, paroxysmal
nocturnal dyspnea and chronic cough.
Physical exam demonstrates hepatojugular reflux, rales, and peripheral
edema. However, these are not present in all those with congestive
heart failure.
The baseline studies are chest x-ray and electrocardiogram. An
echocardiogram may be indicated to evaluate left ventricular and right
ventricular ejection fractions, movement of chamber walls and valves,
and chamber sizes. In systolic dysfunction, ejection fraction is
decreased.
 Pulmonic valve stenosis
Narrowing of the pulmonic valve orifice due to congenital
pulmonic valve abnormalities, most frequently a domed
valve, occasionally bicuspid, with restricted opening.
Pulmonic valve stenosis of varying degree constitutes about
10% of congenital heart disease.
In newborns, pulmonic valve stenosis with severe obstruction to
right ventricular outflow may present as an emergency with
right-to-left atrial shunting. It requires immediate diagnosis: by
electrocardiogram showing diminished right ventricular forces
(when the right ventricular is hypoplastic, which is usually
severe) or right ventricular hypertrophy; by x-ray showing
decreased pulmonary blood flow; by echocardiography,
showing a severely narrowed valve with restricted movement;
and possibly by catheterization and angiography to evaluate
potential right ventricular function.
In older children, cyanosis is not present, although
poor peripheral color may result from prolonged
circulation and a wide arteriovenous oxygen
difference. An ejection murmur, usually with a
prominent ejection click, is found at the upper left
sternal border with an increasingly late peak as
obstruction increases. Electrocardiogram shows
increasingly severe right ventricular hypertrophy. X-
ray shows a normal heart size and a prominent main
pulmonary artery segment with increasingly severe
obstruction. The pulmonary vascular markings are
narrow.
 Primary pulmonary hypertension
A very uncommon obliterative disease of unknown cause
involving medium and small pulmonary arteries resulting
in right ventricular failure or fatal syncope 2 to 5 yr after
detection.
Women are affected twice as often as men. The median age at
diagnosis is 35 yr; younger patients have a worse prognosis.
Intimal hyperplasia and consequent narrowing of the vessel
lumen are always present. Areas of medial hypertrophy and
hyperplasia, irreversible plexiform lesions, and necrotizing
arteritis (plexogenic arteriopathy) occur in more advanced
cases.
Progressive exertional dyspnea occurs in > 95% of cases.
Precordial pain and syncope on exertion are less common.
Raynaud's phenomenon and arthralgias occur in many
patients, often years before the apparent onset of primary
pulmonary hypertension.
Diagnosis is suspected on the basis of clinical
manifestations, but all known causes of cor
pulmonale must be excluded. Physical
examination shows, to a variable extent, the
manifestations of cor pulmonale.
Echocardiography, ventilation/perfusion
scanning, pulmonary function testing, and
cardiac catheterization are usually necessary
to exclude other causes of pulmonary
hypertension. Pulmonary angiography should
be undertaken if ventilation/perfusion scans
show unmatched segmental or larger
perfusion defects.
Treatment
 Oxygen therapy, diuretics, vasodilators, digitalis, theophylline,
and anticoagulation therapy are all different modalities used in
the long-term management of chronic cor pulmonale.
 Oxygen therapy is of great importance in patients with cor
pulmonale particularly when administered on a continuous basis.
Oxygen therapy relieves hypoxemic pulmonary vasoconstriction,
which then improves cardiac output, lessens sympathetic
vasoconstriction, alleviates tissue hypoxemia, and improves renal
perfusion.
 Diuretics are used in the management of chronic cor pulmonale,
particularly when the right ventricular filling volume is markedly
elevated. Diuretics may result in improvement of the function of both
the right and left ventricles; however, diuretics may produce
hemodynamic adverse effects if they are not used cautiously.
Excessive volume depletion can lead to decline in cardiac output.
Another potential complication of diuresis is the production of a
hypokalemic metabolic alkalosis, which diminishes the effectiveness
of carbon dioxide stimulation on the respiratory centers and lessens
ventilatory drive. Therefore, diuretics, while recommended in the
management of chronic cor pulmonale, needs to be used with great
caution.
 Vasodilator drugs have been advocated in the long-term
management of chronic cor pulmonale with modest results.
Calcium channel blockers, particularly oral sustained-release
nifedipine and diltiazem, can lower pulmonary pressures,
although they appear more effective in primary rather than
secondary pulmonary hypertension. Right heart catheterization
has been recommended during initial administration of
vasodilators to objectively assess the efficacy and detect the
possible adverse hemodynamic consequences of vasodilators.
 The use of cardiac glycosides, such as digitalis, in patients
with cor pulmonale has been controversial, and the beneficial
effect of these drugs is not as evident as in the setting of left
heart failure. Nevertheless, studies have confirmed a modest
effect of digitalis on the failing right ventricle in patients with
chronic cor pulmonale. It must be used cautiously, however, and
should not be used during the acute phases of respiratory
insufficiency when large fluctuations in levels of hypoxia and
acidosis may occur. Patients with hypoxemia or acidosis are at
increased risk of developing arrhythmias due to digitalis.
 Theophylline has been reported to reduce pulmonary
vascular resistance and pulmonary arterial pressures in
patients with chronic cor pulmonale. Theophylline has a
weak inotropic effect and thus may improve right and left
ventricular ejection.
 Anticoagulation with warfarin is recommended in
patients at high risk for thromboembolism. The beneficial
role of anticoagulation in improving the symptoms and
mortality in patients with primary pulmonary arterial
hypertension clearly was demonstrated in a variety of
clinical trials. The evidence of benefit, however, has not
been established in patients with secondary pulmonary
arterial hypertension. Therefore, anticoagulation therapy
may be used in patients with cor pulmonale secondary to
thromboembolic phenomena and with underlying primary
pulmonary arterial hypertension.
Further inpatient care
Appropriate treatment is directed both at the
underlying etiology and at correction of
hypoxia when present.
Further outpatient care
 Patients with cor pulmonale generally require

close attention in the outpatient setting.

 Regular assessment of oxygen needs and

pulmonary function are appropriate.

 Many patients benefit from a formal program

of pulmonary
Complications
Complications of cor pulmonale include syncope,
hypoxia, pedal edema, passive hepatic congestion,
and death.
Prognosis
 The prognosis of cor pulmonale is variable
depending upon underlying pathology.
 Patients with cor pulmonale due to chronic
obstructive pulmonary disease have a high 2-year
mortality.
Patient education:
Patient education regarding the importance of
adherence to medical therapy is vital because
appropriate treatment of both hypoxia and
underlying medical illness can improve mortality and
morbidity.