Respiratory Medicine PEER REVIEWED UPDATES FOR MEDICAL PRACTITIONERS Today Pulmonary hypertension A rare but important cause of dyspnoea A REPRINT FROM APRIL 2019 THIS REPRINT IS SPONSORED AS AN EDUCATIONAL SERVICE BY ACTELION, A BUSINESS UNIT OF JANSSEN-CILAG PTY LTD ACN 000 129 975 1-5 KHARTOUM RD MACQUARIE PARK NSW 2113, AUSTRALIA TELEPHONE: 1800 226 334 www.janssen.com/australia DATE OF PREP: JULY 2019 CP-100012 © 2019 MEDICINE TODAY PTY LTD FEATURE PEER REVIEWED Pulmonary hypertension A rare but important cause of dyspnoea DAVID MICHAIL MB BS, FRACP; MEERA SRINIVASAN MB BS(Hons) Pulmonary hypertension can be a devastating disease that is easily missed in the early stages because of its typically nonspecific presentation with gradually increasing dyspnoea. With advances in management, most forms of pulmonary hypertension are treatable. Early diagnosis and treatment are key to improving functional and haemodynamic outcomes and survival. ulmonary hypertension (PH) is to a mean pulmonary artery pressure of a pathophysiological condition more than 20 mmHg, was recently pro- characterised by an increase in posed.1 If untreated, PH can be a devas- the mean pulmonary artery tating condition with high morbidity, and Ppressure. It is defined by a mean pulmo- mortality rates that are poorer than for nary artery pressure of 25 mmHg or higher many metastatic malignancies. Increased at rest, measured during right-heart recognition of patients with PH, allowing cath eteri sation. A change to this threshold, early diagnosis and intervention, is the focus of current management campaigns to alter the natural history of this disease. Classification of pulmonary hypertension small pu lmonary arteries leading RESPIRATORY MEDICINE TODAY 2019; 4(1): 6-12 Conditions that cause PH are classified by to increased pulmonary vascular the WHO into five major groups based on resistance are the primary Dr Michail is a Respiratory and Sleep Physician shared pathophy siological mechanisms, abnormality and Director of the Pulmonary Hypertension Expert which guide the therapeutic approach. • Group 2 – PH secondary to left heart Centre at Westmead Hospital, Sydney; and Chair The WHO diagnostic groups are: disease of the Pulmonary Arterial Hypertension Committee, • Group 1 – also known as pulmonary • Group 3 – PH secondary to chronic Lung Foundation Australia. Dr Srinivasan is an arterial hypertension (PAH); lung disease or hypoxia Advanced Trainee in Respiratory and Sleep Medicine this group comprises conditions • Group 4 – chronic thromboembolic at Westmead Hospital, Sydney, NSW. where obstructive changes to the PH, typically a sequela of unresolved © BAYER. PULMONARY ARTERIAL HYPERTENSION 2 RespiratoryMedicineToday Key points • Pulmonary hypertension (PH) is characterised by an elevation in pulmonary artery pressure at rest and presents with progressive breathlessness as the cardinal symptom. • PH can be associated with more than 50 different conditions, which are categorised into five groups based on pathophysiological mechanisms; accurate classification is crucial to management as treatment options and goals vary between groups. • As symptoms of PH can be vague or nonspecific, diagnosis is often delayed, with patients typically progressing to advanced disease before diagnosis. • Identifying patients early in the disease course can improve functional and haemodynamic outcomes. • Group 1 PH (pulmonary arterial hypertension [PAH]) is rare; if it is suspected then prompt referral of the patient to a specialist with an expert interest in PH is recommended. • Long-term management of patients with PAH, Group 4 (chronic thromboembolic) or Group 5 (unclear or multifactorial) PH should be delivered or co-ordinated through a designated PH clinic or service. pulmonary embolism is crucial to ensuring management is tar- Group 1. Pulmonary arterial • Group 5 – PH with unclear or geted to the underlying pathophy siology. hypertension multifactorial mechanisms.2 For example, selective pulmonary vaso- PAH (Group 1 PH) is a progressive and Conditions included in the five WHO dilators are the only proven drug therapies often devastating condition. Proliferative diagnostic groups are listed in Box 1.2 for patients with PAH and Group 4 PH. changes in the lung microcirculation lead These WHO diagnostic groups aredi stinct However, their use to treat patients with PH to increased pulmonary vascular resistance. from the WHO functional class system in other groups may precipitate pulmonary If untreated, this results in right heart (Classes I to IV), which was adapted from oedema or other adverse cardiac events remodelling and ultimately right heart the NYHA functional class system. (Group 2 PH) or exacerbate hypoxia and failure and death. Historically, patients with Accurate diagnosis of the PH group breathlessness (Group 3 PH). PAH had a grim prognosis, but in the past RespiratoryMedicineToday 3 FEATURE PULMONARY HYPERTENSION CONTINUED 1. WHO classification of pulmonary hypertension2 1. Pulmonary arterial hypertension 2. Pulmonary hypertension due to 4. Chronic thromboembolic pulmonary 1.1 Idiopathic left heart disease hypertension and other pulmonary artery 1.2 Heritable 2.1 Left ventricular systolic dysfunction obstructions 1.3 Drug and toxin induced 2.2 Left ventricular diastolic dysfunction 5. Pulmonary hypertension with unclear 1.4 Associated with: 2.3 Valvular disease and/or multifactorial mechanisms 1.4.1 connective tissue disease 2.4 Congenital/acquired left heart 5.1 Haematological disorders: 1.4.2 HIV infection inflow/outflow tract obstruction and myeloproliferative disorders, 1.4.3 portal hypertension congenital cardiomyopathies splenectomy 1.4.4 congenital heart diseases 2.5 Other 5.2 Systemic disorders: sarcoidosis, 1.4.5 schistosomiasis 3. Pulmonary hypertension due to lung pulmonary Langerhans cell 1’. Pulmonary veno-occlusive disease disease and/or hypoxia histiocytosis, lymphangioleiomyomatosis, and/or pulmonary capillary 3.1 Chronic obstructive pulmonary disease neurofibromatosis, vasculitis haemangiomatosis 3.2 Interstitial lung disease 5.3 Metabolic disorders: glycogen 1’’. Persistent pulmonary hypertension 3.3 Other pulmonary diseases with mixed storage and Gaucher disease, of the newborn obstructive and restrictive patterns thyroid disorders 3.4 Sleep-disordered breathing 5.4 Others: tumoural obstruction, fibrosing 3.5 Alveolar hypoventilation disorders mediastinitis, chronic renal failure on 3.6 Chronic exposure to high altitude dialysis 3.7 Developmental lung diseases 15 to 20 years their functional status and life the pulmonary arteries in the setting of the diagnosis of PH is often overlooked, expectancy have improved significantly with mechanical obstruction by unresolved contributing to delayed management. major developments in targeted drug thrombus. The underlying pathophysiology Particularly in patients with PAH or Group treatments. is similar to that of PAH. Where possible, 4 PH, opportunities are often missed to surgical intervention with pulmonary diagnose and treat disease at an early, poten- Group 2. PH secondary to left endarterectomy is the preferred treatment, tially reversible stage before significant heart disease as it has the potential to ‘cure’ PH. However, pulmonary vascular remodelling. A high PH secondary to left heart disease (e.g. inter ventional radiological approaches or index of suspicion is required as id entifying ventricular or valvular disease) is the most targeted drug therapy can be used in patients patients early in the disease course and common type of PH. Treatment of the under- deemed unsuitable for surgery because of referring them to specialists with specific lying disease and risk factor modification their pulmonary vasculature status, comor- expertise in PH can improve functional and are key to management. Stiffness of the left bidities or functional state. haemodynamic outcomes (see the case ventricle (heart failure with preserved history in Box 2).3,4 ejection fraction) is increasingly identified Group 5. PH with unclear or as a cause of PH. multifactorial mechanisms Diagnosis Group 5 PH includes conditions whose Diagnosis of PH requires a comprehensive Group 3. PH secondary to lung pathophysiology does not fit within set of investigations to confirm that haemo- disease or hypoxia Groups 1 to 4 PH. The mechanism driving dynamic criteria are met and to identify PH secondary to lung disease, sleep- abnormal pulmonary artery pressures in the aetiology and severity of the condition. disordered breathing or hypoxia is rela- patients with Group 5 PH is often unclear. Involvement of a multidisciplinary team tively common. Optimising the underlying The most common cause of PH in this group with expertise in cardiology, respiratory condition with appropriate therapy, sup- is sarcoidosis. medicine, imaging and connective tissue plemental oxygen and respiratory support diseases is recommended. Given the com- is the key to management. Typically, Presentation plexity of managing patients with PH, patients do not benefit from targeted drug Clinical features of PH are nonspecific and referral to a clinic with expert medical, treatment. include dyspnoea, fatigue, generalised nursing, pharma cological and psycholog- weakness and, in later stages, chest pain, ical support is also recommended. Group 4. Chronic thromboembolic PH syncope and evidence of right heart failure. A diagnostic algorithm that highlights Chronic thromboembolic PH is thought to Given the nonspecific nature of these symp- the complexities involved in