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.
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.
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.
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.