Pulmonary Hypertension
Pulmonary hypertension (PH) is define as a mean pulmonary artery (PA)
pressure of more than 25 mmHg at rest or more than 30 mmHg during
exercise (normal value ~ 14 mmHg mean). A rise in PA pressure can be due to
increased pulmonary vascular resistance (e.g. hypoxia and embolism),
pulmonary blood flow and back-pressure (pulmonary venous pressure, e.g.
left heart failure). PH is most commonly caused by another disorder (secondary
PH). More rarely it is due to a disorder of the pulmonary circulation
itself, when it is termed pulmonary arterial hypertension (PAH).
Idiopathic PAH (IPAH) has no apparent cause. The Venice (WHO) classificatio of
PH is shown in Fig. 27a.
Types of pulmonary hypertension
Secondary to respiratory disease: most common, due to hypoxaemia which causes small
pulmonary arteries to constrict (hypoxic pulmonary vasoconstriction). PH
is often associated with COPD (Chapter 26). Any condition leading to hypoxia
can cause PH, including sleep-disordered breathing (Chapter 44) and exposure to
altitude (Chapter 15).
Pulmonary venous hypertension: increased left atrial (LA) pres- sure, most
commonly due to left ventricular dysfunction as in congestive heart failure,
leads to elevation of PA pressure by increasing back-pressure through the
lungs. Mitral insufficiency or stenosis may also increase PA
pressure enough to cause hypertension. In these cases, patients will often have
signs of pulmonary capillary hypertension such as crackles. Echocardiography
should demonstrate LA enlargement.
Secondary to thrombotic disease: acute and chronic venous thromboembolism causes
PH by mechanical obstruction of the proximal or distal pulmonary arteries. In
acute thromboembolism, a component of vasospasm is also present, as the
platelet-rich thromboem- bolus releases vasoactive mediators such as
thromboxane, serotonin or platelet-activating factor. This form is also
associated with sickle cell disease.
Disorders directly affecting the
vasculature: increases in pulmonary
vascular resistance may occur in the veins, capillaries or arteries. Increases
in capillary resistance are common and may occur in any lung disease
that causes capillary distortion or reduction in surface area. Interstitial
lung diseases (Chapters 30 & 31) such as pulmonary fibrosis, scleroderma
or sarcoidosis cause capillary distortion, as lung parenchyma is
affected. Destruction of capillaries occurs in emphysema (Chapter 26) or
pneumonectomy. In schistosomiasis (bilharzia) the parasitic worms can block
pulmonary capillaries.
Pulmonary arterial hypertension includes IPAH, PH associated with conditions such
as collagen vascular disease, HIV and portal hypertension but where no causal
relationship can be determined, and persistent pulmonary hypertension of the
newborn (PPHN). IPAH is rare (1-2 per million population) and its pathogenesis
is unclear. Genetic abnormalities, in particular related to bone morphogenic
protein and serotonin transporters, may predispose patients to IPAH, but
although some cases are clearly familial with autosomal dominant
inheritance, other are sporadic with no family history. IPAH is more
common in women than men (ratio 2:1) and most prevalent between 20 and 40 years
of age. Certain appetite-suppressant drugs affecting serotonin (e.g.
fenfluramine are associated with a 30-fold increase in risk after 3 months.
Remodelling of pulmonary arterioles is characteristic of IPAH, although in some
patients a component of arterial vasospasm is suggested by the effect of
vasodilators.
Clinical features
Development of PH can substantially
increase morbidity and mortal- ity. The prognosis for COPD patients with PH is
much worse, with a 5-year survival for of less than 10% if PA pressure is more
than 45 mmHg compared with more than 90% with PA pressure less than 25 mmHg.
Mean survival without treatment in IPAH is 2 years. Patients usually die from progressive
right-sided heart failure. Chronic PH can lead to pulmonary vascular remodelling
and thickening of the pulmonary vasculature, reducing the effica y of
vasodilators. PH is generally slow to develop and presents with non-specifi
symptoms, including dyspnoea on exertion, shortness of breath, palpitations,
chest pain, light-headedness and syncope. Signs are difficul to elicit early
and may only include an increased pulmonic component of the second heart sound.
With more severe hypertension, right ventricular dysfunction will be
apparent, including jugular venous distension, right ventricular heave, pedal
oedema and hepatic enlargement. Detection of PH requires a high index of
suspicion, because signs and symptoms are non-specifi and the diagnosis
requires further testing; there is significan underdiagnosis.
Diagnosis
Evaluation of patients with suspected
PH (Fig. 27b) begins with echocardiography, allowing calculation of
right ventricular systolic pressure and visualization of left atrium (LA),
mitral valve, right ventricle and congenital abnormalities. If PH is found in
conjunction with an enlarged LA, it is most likely due to either left
ventricular or mitral disease. Chest radiology, pulmonary function testing and
measurement of arterial oxygen allow detection of parenchymal disease or
hypoxia. In the absence of LA enlargement or pulmonary parenchymal disease,
further evaluation of pulmonary arteries is necessary. Ventilation/perfusion
scanning is most useful to demonstrate chronic thromboemboli (Chapter 28). Right
heart catheterization is the definit ve test for the assessment of PH, as
PA pressure can be measured directly and LA pressure estimated from the
pulmonary capillary wedge pressure. Patients with PH without an elevated LA
pressure and no apparent pulmonary venous, lung parenchymal, chronic thromboemboli
or congenital heart disease are assumed to have IPAH.
Treatment
Therapy in most patients is directed
at the underlying abnormality, to relieve right ventricular strain and prevent
right-sided heart failure. Hypoxaemic patients with COPD benefi from O2
therapy to diminish hypoxic vasoconstriction. Patients with thromboembolic
disease (Chapter 28) should receive anticoagulation and evaluation for surgical
thromboembolectomy. Patients with IPAH should also receive anticoagulation to
prevent microthrombi or the devastating effect of an acute thromboembolus
(Chapter 28). There have been major advances in pharmacological therapy for PAH
over the past few years. Type 5 phosphodiesterase inhibitors (e.g. sildenafil
increase cGMP and consequently augment vasorelaxation and reduce vascular remodelling.
Endothelin-receptor antagonists (e.g. bosentan, dual ETA and ETB
antagonist) block the action of endothelin-1, a potent vasoconstrictor and
inducer of proliferation, the level of which correlates with PH severity.
Trials have shown that both these drugs improve function, symptoms, exercise
capacity and haemodynamics in PAH. Chronic infusions or nebulization of prostacyclin
analogues improves survival, partially through vasodilatation, though
effects on pulmonary vascular remodelling or endothelial function may explain
its positive long-term effect. Lung transplantation is reserved for failed
medical therapy.
