REVIEW ARTICLEPulmonary hypertension and pregnancy
Introduction
Pulmonary hypertension is defined by a mean pulmonary artery pressure >25 mmHg at rest or >30 mmHg with exercise. Table 1 gives a classification of pulmonary hypertension devised at the World Conference on Pulmonary Hypertension (Venice 2003). The term pulmonary arterial hypertension (PAH) denotes a series of apparently unrelated disorders many of which share the histopathological entity of plexogenic pulmonary arteriopathy (PPA). To make the diagnosis of PAH the mean pulmonary capillary wedge pressure should be <15 mmHg. In patients who have pulmonary hypertension secondary to cardiac disease (e.g. mitral valve disease, ischaemic heart disease) the pulmonary capillary wedge pressure is usually >15 mmHg. Usually the elevation in mean pulmonary artery pressure in patients with PAH is significantly higher than in patients who have pulmonary hypertension secondary to cardiac and pulmonary disorders.
With increasing experience there is a view that the lung can respond to injury via a finite series of pathways. For example multiple causes are implicated in the development of acute respiratory distress syndrome and yet the pathophysiology is similar regardless of aetiology. Similarly patients may develop PPA in association with an apparently unrelated group of conditions. Examples include idiopathic or familial PAH and PAH associated with ingestion of slimming pills, scleroderma, hepatic cirrhosis, human immunodeficiency virus (HIV) infection and Eisenmenger’s syndrome. The underlying mechanisms linking these dissimilar disorders to a final common histological presentation are not clear.
Pulmonary hypertension can also occur in association with cardiac diseases such as left ventricular failure, chronic left atrial hypertension with mitral valve disease and respiratory disorders such as chronic obstructive pulmonary disease (COPD), interstitial lung disease, disorders of pulmonary development and sleep apnoea syndrome. Patients may develop chronic pulmonary thromboembolism from no apparent cause or in association with thrombophilia abnormalities including protein S and C deficiencies or abnormalities in factor V. Prothrombotic states can also accompany connective tissue disorders and malignant disease. Pulmonary hypertension can occur secondary to chronic pulmonary embolic disease and may also accompany more unusual conditions such as lymphangioleiomyomatosis.
Traditionally idiopathic PAH was described in young females although with increasing awareness the condition is now diagnosed in patients beyond the fourth and fifth decades of life. The incidence and prevalence of idiopathic PAH are estimated to be four per million per year and 10 per million of the population respectively. Overall the prevalence of PAH may be in the region of 100 per million of the population but the incidence and prevalence of pulmonary hypertension associated with cardiac and respiratory disorders are likely to be much higher.
PAH is associated with a poor survival and a poor quality of life. At present there is no cure, understanding of the disease is incomplete and treatment options are limited.
Section snippets
Pathology
In pulmonary hypertension associated with known cardiac or pulmonary disorders, typical pathological features associated with the primary condition will be present. The pathology in these conditions is quite distinct from that in PPA. The initiating factors in the development of PPA are not known. There is initial vasoconstriction and subsequently smooth muscle migration from the inner half of the media of muscular pulmonary arterioles into the vessel lumen. These cells become myofibroblasts
Symptoms
Initially, patients with PAH may be asymptomatic or they may develop dyspnoea with exertion. This non-specific symptomatology may lead to failure of diagnosis or to an incorrect diagnosis such as depression. As the condition progresses, pulmonary vascular resistance (PVR) rises, cardiac output falls and patients may experience dyspnoea, palpitations, chest pain (due to right ventricular angina) pre-syncope or syncope. Initially these symptoms may arise with exertion but subsequently occur at
Clinical signs
The clinical features of pulmonary hypertension may be subtle and therefore missed on physical examination. Important features include a loud pulmonary component to the second heart sound, an early systolic ejection click, a mid-systolic ejection murmur and a right ventricular fourth heart sound. Other features include a palpable left parasternal lift, a prominent jugular a wave, a diastolic murmur of pulmonary regurgitation and a pan-systolic murmur of tricuspid regurgitation. This latter
Disease progression
As the disease progresses PVR rises, cardiac output falls and further right ventricular dysfunction and tricuspid regurgitation evolve, leading to right heart failure and death (Fig. 1). Disease progression and response to therapy can be assessed using the World Health Organisation classification of functional capacity, which is an adaptation of the New York Heart Association (NYHA) classification (Table 2).
Investigations
In addition to aetiology (above), the following investigations are useful in predicting mortality in PAH:
- 1.
Functional capacity (NYHA or PAH class)
- 2.
Exercise capacity (unencouraged six-minute walk test)
- 3.
Haemodynamics (severity of right ventricular dysfunction)
- 4.
Echocardiographic parameters.
The unencouraged six-minute walk test is easy to perform and a reproducible means of assessing exercise capacity in patients with PAH; it may be an independent predictor of survival.6 Right heart catheterisation can
Physiological considerations
Many maternal physiological changes occur during pregnancy but those of greatest significance for the patient with PAH relate to blood volume, cardiac output, pulmonary and systemic vascular resistance and clotting mechanisms.
Maternal blood volume increases throughout pregnancy until between 28 and 34 weeks of gestation when a plateau occurs until delivery. The circulating blood volume is increased to between 30% and 50% above the non-pregnant state by the end of pregnancy. Most of this
Conclusion
Pregnant women with PAH present a major challenge because of pre-existing cardiorespiratory disease together with the circulatory changes and increased coagulability associated with pregnancy. As maternal mortality is between 30% and 50%, pregnancy is best avoided and some advocate termination. Should patients proceed with pregnancy they require careful monitoring by a multidisciplinary team. Most maternal deaths occur in the third trimester or post partum, and treatment options at this stage
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