Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension (PAH):
Disease and Management Overview
PAH is a chronic, progressive disease characterised by an increase in pulmonary vascular resistance (PVR) leading to right ventricular overload and, eventually, to right ventricular failure. The increase in PVR is due to evolving pathological changes in the pulmonary vasculature such as vasoconstriction, inflammation, fibrosis, vascular remodelling and in-situ thrombosis. Developing PAH leads to an increasing restriction of blood flow through the pulmonary arteries and right heart hypertrophy, causing non-specific symptoms such as dyspnoea, chest tightness, limited exercise capacity and fatigue.1-3

PAH Diagnosis
Diagnosis is often delayed due to the equivocal symptoms of PAH, with dyspnoea and fatigue the most common early symptoms for which patients initially seek medical attention.2,3 Investigations required to detect the possible presence of PAH include chest X-ray, ECG, blood tests and immunology, pulmonary function tests, Doppler echocardiogram, ventilation and perfusion lung (V/Q) scan and high resolution computed tomography (CT) heart/lung scans. 1-3 Definitive diagnosis is determined by right heart catheterisation revealing:1
• Mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg at rest
• Pulmonary wedge pressure (PWP) ≤ 15 mmHg
• Cardiac output normal or reduced.

PAH Classification
PAH may occur for no apparent reason – idiopathic PAH (IPAH) – or may be inherited (heritable PAH [HPAH]). Various disease states are also associated with an increased risk of developing PAH e.g. scleroderma and other connective tissue diseases, and congenital heart defects (CHD).4 Patients with scleroderma should be screened annually for early detection of PAH due to the increased risk of developing the disease. Similarly, patients with a history of CHD should be monitored for symptoms suggestive of the development of Eisenmenger’s syndrome (defined as severe PAH associated with intra- or extra-cardiac shunt which over time leads to flow reversal and cyanosis).3
PAH is considered a rare disease with an estimated prevalence of 15 cases per million.5 However, in certain patient groups the prevalence is substantially higher e.g. PAH associated with scleroderma has a reported prevalence of up to 26%.6 However, the true prevalence of all forms of PAH is believed to be under-estimated due to delayed and/or missed diagnosis.

PAH Treatment
PAH is a devastating disease for which there is no cure. Without treatment, PAH can progress rapidly even in mildly symptomatic patients.2 Disease severity is assessed using the New York Heart Association (NYHA) functional classification, adapted to PAH by the World Health Organisation (WHO).3
Treatment for PAH has improved markedly in the past two decades with improved knowledge of the endogenous changes thought to be fundamental to disease development. Increased levels of endothelin and decreased levels of prostacyclin and nitric oxide are now targeted by endothelin receptor antagonists, prostacyclin analogues and phosphodiesterase 5 (PDE-5) inhibitors, respectively, with clinical benefit demonstrated. In Australia, PAH-specific treatments are funded via the Pharmaceutical Benefits Scheme.7 Supportive therapy with oral anticoagulants, diuretics and oxygen therapy may also be a part of management.1-3

PAH Management – a Multidisciplinary Approach with Primary Care Support
With the introduction of PAH-specific treatments, patients now typically face a chronic progressive disease requiring ongoing medical management in a multidisciplinary approach which may include cardiology, respiratory and rheumatology, as well as general practice, specialised nursing staff, pharmacy, physiotherapy and other healthcare providers. In Australia, specialised treatment is received within PAH Designated Centres which, in partnership with primary care and other healthcare professionals, provide support and assistance in monitoring patients’ evolving condition, treatment and specific needs.3

References:
1. Galie` N et al. Eur Heart J. 2009;30(20):2493-537. 2. Humbert M. Am J Respir Crit Care Med 2008;177:574–579. 3. Gibbs JSR et al. Heart 2008;94(Suppl I):i1–i41. 4. Simonneau G et al. JACC 2009;54(1 Suppl S):S43-S54. 5. Humbert M et al. Am J Respir Crit Care Med 2006;173:1023–30. 6. Badesch DB et al J Am Coll Cardiol 2009;54(1 Suppl S):S55-S66. 7. Pharmaceutical Benefits Scheme (PBS): www.pbs.gov.au

RESOURCES:
Queensland Pulmonary Hypertension Treatment Centres