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cont....
Pulmonary Hypertension of the Newborn
Persistent pulmonary hypertension of the newborn is to
be distinguished from congenital abnormalities of the
heart and pulmonary vasculature. It represents an entity
similar to PPH and is typically somewhat more responsive
to acute and chronic vasodilator therapies.11 Untreated,
it can be rapidly fatal.
Other Causes of Pulmonary Hypertension
Pulmonary Venous Hypertension
- Left-sided atrial or ventricular
heart disease
- Left-sided valvular heart disease
- Extrinsic compression of central
pulmonary veins
(a) Fibrosing mediastinitis
(b) Adenopathy/tumors
- Pulmonary veno-occlusive disease
- Other
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Pulmonary venous hypertension represents a clinical entity
that has a pathophysiology and clinical course that is
markedly different from pulmonary arterial hypertension.
Orthopnea and paroxysmal nocturnal dyspnea are characteristic
features, which may precede effort dyspnea. These patients
often have a history of chronic congestive heart failure
and/or recurring pulmonary edema, which then becomes obscured
when right ventricular failure ensues. Pulmonary venous
hypertension is the most common cause of pulmonary hypertension
in clinical practice. Because blood by necessity flows
through the pulmonary vascular bed into the left heart,
any elevation of the filling pressure of the left side
of the heart will result in an increase in pulmonary artery
pressure. Although often times this is quite apparent,
there are some circumstances where the situation is confusing.
For example, chronic pulmonary venous hypertension can
lead to morphologic changes in the pulmonary arterial
and venous bed resulting in further elevation of the pulmonary
artery pres-sure beyond that which was initially a result
of the elevated left-sided pressure, implying pulmonary
vasoconstriction or a vasculopathy triggered by the elevation
in pulmonary venous pressure. Often, the physician is
confronted as to whether or not two processes are ongoing
or the long-term result of a sin-gle process. Another
scenario is the patient who has a longstanding history
of left heart disease who develops pulmonary hyperten-sion
and severe right heart failure. At the time of cardiac
catheterization these patients may have a normal pulmonary
capillary wedge or left ventricular end diastolic pressure
in the presence of a low cardiac output. Thus, they may
have the hemodynamic profile of a patient with PPH because
one is unable to determine what the left ventricular end
diastolic pressure would be in the face of a normal cardiac
output. The diagnosis of pulmonary veno-occlusive disease
can be difficult, since the pulmonary wedge pressure may
be nor-mal or elevated depending on the segment of the
lung that is measured. In our experience these patients
often have a very abnormal perfusion lung scan without
any evidence of pul-monary thromboembolic disease.12 Another
common, but inconsistent, feature is an elevation in pulmonary
capillary wedge pressure following the challenge of an
infusion of adenosine or prostacyclin at the time of catheterization.
Pulmonary Hypertension Associated
With Disorders of the Respiratory System and/or Hypoxemia
- Chronic obstructive pulmonary
disease
- Interstitial lung disease
- Sleep-disordered breathing
- Alveolar hypoventilation disorders
- Chronic exposure to high altitude
- Neonatal lung disease
- Alveolar-capillary dysplasia
- Other
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Although hypoxemia may coexist in all forms of pulmonary
hypertension, it is the hallmark of these conditions.
These patients are often dyspneic at rest as well as with
minimal activity, with only subtle clinical features of
pulmonary hyper-tension. Supplemental oxygen will usually
provide substantial clinical improvement.
A subset of patients present with severe elevations in
pul-monary artery pressure beyond those typically seen
in these disease entities.13 Whether this represents an
extreme mani-festation of the underlying disease or a
different disease process characteristic of pulmonary
arterial hypertension that has been triggered by a common
pathway is currently unknown. Clinically, it can be difficult
to sort out the basis of a patient’s complaint of
dyspnea. In addition, even successful treatment of the
pulmonary hypertensive component of the problem may not
render the patient clinically improved if the hypoxemia
persists. Of great concern is that some therapies directed
toward the pulmonary hypertension can worsen gas exchange
and make the hypoxemia even worse.
Pulmonary Hypertension Due to Chronic
Thrombotic or Embolic Disease
- Thromboembolic obstruction of
proximal pulmonary
arteries
- Obstruction of distal pulmonary
arteries
(a) Pulmonary embolism (thrombus, tumor, ova and/or
parasites, foreign material)
(b) In-situ thrombosis
(c) Sickle-cell disease
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These patients often present with clinical signs and
symptoms that are indistinguishable from pulmonary arterial
hypertension. Unless a thorough evaluation is conducted
to exclude these diseases, patients may be misdiagnosed
and inappropriately treated. Chronic proximal thromboembolic
obstruction of the pulmonary arteries is a well characterized
clinical entity that has been extensively studied.14 Because
it is potentially reversible, it must be excluded in every
patient who presents with pulmonary hypertension irrespective
of the lack of an antecedent history of deep vein thrombosis
or pulmonary thromboembolism. Obstruction of the distal
pulmonary arteries can be either embolic or thrombotic.
Recurrent microthromboembolism does not appear to be a
clinical entity, since current evidence points to thrombosis
in situ as being responsible for the thrombotic changes
noted in the arteriolar bed in patients with pulmonary
arterial hypertension. Thrombotic obstruction, however,
can occur anywhere from the pulmonary capillary bed to
the main pulmonary arteries and may reflect a continuum
of a disease process. This makes it difficult to ascertain
the cause of pulmonary hypertension in a patient with
clear evidence of pulmonary thromboembolism involving
a relatively few number of vessels. It appears that in
some of these
patients thrombotic obstruction of the pulmonary arteries
leads to chronic pathologic changes in the uninvolved
vascula-ture. Diffuse pulmonary embolism can occur on
rare occa-sions from metastatic tumors, parasitic disease,
or from foreign material through intravenous injection.
Pulmonary Hypertension Due to Disorders
Directly Affecting the Pulmonary Vasculature
- Inflammatory
(a) Schistosomiasis
(b) Sarcoidosis
(c) Other
- Pulmonary capillary hemangiomatosis
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These very rare entities require a high index of suspicion
in order for a diagnosis to be made. Schistosomiasis,
for example, is probably the most common cause of pulmonary
hypertension worldwide, although it is virtually never
seen in
Westernized countries. It should be kept in mind when
patients are referred from underdeveloped countries as
a potential underlying etiology.
Sarcoidosis can cause extensive destruction of the pulmonary
parenchyma and pulmonary vascular bed and can cause pulmonary
hypertension merely by lung destruction and resulting
hypoxemia. In addition, these patients may develop
pulmonary hypertension presumed to be on the basis of
involvement of the pulmonary circulation from the sarcoid
process. It is unlikely that this is due to local granuloma
formation within the pulmonary vasculature and is more
likely
the result of growth factors triggering the same process
that is seen in pulmonary arterial hypertension. Some
of these patients may respond very favorably to long-term
intravenous epoprostenol.15 Pulmonary capillary hemangiomatosis
is an extremely rare disorder involving the pulmonary
capillary bed that can pres-ent
in different stages. It is often associated with frequent
hemoptysis, severe pulmonary hypertension, and a progressive
fatal course in a short period of time. The diagnosis
can be made with pulmonary angiography in the hands of
an experi-enced radiologist. PH
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- Rich S. Primary pulmonary hypertension. Progress
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- Rich S, Dantzker DR, Ayres SM, et al. Primary pulmonary
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- Deng Z, Haghighi F, Helleby, et al. Fine mapping
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- Rich S, Kieras K, Hart K, et al. Antinuclear antibodies
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- Brickner M, Hillis L, Lange R. Congenital heart disease
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- Clark R, Kueser T, Walker M, et al. Low-dose nitric
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- Stevens D, Sharma K, Szidon P, et al. Severe pulmonary
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