Pulmonary hypertension (PHT) is elevated pressure of blood flowing from the right side of the heart, through the lungs and back to the left side of the heart. PHT can be predominantly right sided (arterial/ precapillary/PAH) , left sided (venous / postcapillary/PVH) or mixed. This can result in high pressure on the right side of the heart, which can eventually fail.
There are 5 main classifications or groups of causes:
Group 1 PHT is due to small blood vessel inflammation and narrowing caused by idiopathic pulmonary arterial hypertension (iPAH), hereditary (hPAH) and PAH associated with connective tissue diseases, congenital heart disease or drug-induced PAH (diet pills, cocaine, cancer treatments).
Group 2 PHT is caused by back pressure from left-sided heart disease such as cardiomyopathy or valvular disorders.
Group 3 PHT is due to damaged lung vessels from diseases such as emphysema, pulmonary fibrosis or sleep apnoea.
Group 4 PHT is secondary to multiple blood clots in the lung vessels called chronic thromboembolic disease or CTEPH.
Group 5 PHT is due to unclear mechansisms associated with other conditions such as sarcoidosis and blood cancers (5).
The diagnosis of PHT requires the following investigations: chest X-ray, ECG, autoimmune screen, thyroid function, sarcoid screen, pulmonary function tests, Cardiopulmonary exercise test (CPET), 6 minute walk test, Doppler echocardiogram, ventilation and perfusion lung (V/Q) scan, and high-resolution computed tomography (CT) lung scans.
Definitive diagnosis is determined by right heart catheterisation (RHC), generally performed via the right neck (internal jugular), elbow (basilic) or groin (femoral) vein, to directly assess blood pressures in the heart and lung. Sometimes a vasodilator challenge to assess reactivity of pulmonary vessels and/or fluid challenge to assess for a stiff heart may be performed at the time of right heart catheterisation. An exercise bike may be used during the procedure to simulate exertion.
Exertional breathlessness and fatigue are the most common symptoms for which medical attention is initially sought. The presentation of such non-specific symptoms often contributes to the delay in diagnosis. In Australia, patients reported on average, five general practitioner visits and three specialist reviews, and a delay of nearly four years from symptom onset to a diagnosis of Idiopathic PAH.
Risk factors include being female (although males have longer delay to diagnosis), connective tissue disorders, positive family history, use of diet pills, sleep apnoea, pulmonary fibrosis, emphysema, thromboembolic disease and heart failure.
General measures for treatment of PAH include structured physical activity and lifestyle measures, avoidance of pregnancy and infection prevention. Oxygen therapy, anticoagulation (for WHO Group 1 and CTEPH) and diuretics may be required.
PAH (Group 1) is characterised by increased levels of endothelin and decreased levels of prostacyclin and nitric oxide. As a result, three pathways are the focus of current medical treatment options for PAH:
1. Prostanoids such as inhaled iloprost, intravenous epoprostanol, oral treprostenil or Prostacyclin receptor agonists (Selexipag).
2. Nitric oxide donors such as phosphodiesterase (PDE)-5 inhibitors (sildenafil and tadalafil) or soluable guanlylate cyclase stimulators (riociguat)
3. Endothelin receptor antagonists (ERA) such as ambrisentan , macitentan or bosentan.
4. Calcium channel blockers (eg diltiazem) may be used if there is evidence of vasoreactivity during right heart catheterisation.
Group 1 PAH have the best response to medical therapy.
Group 2 or left sided (pulmonary venous hypertension) treatment is less well established and centres around fluid management (diuretics) and correction of valvular disorders with treatment of systolic dysfunction and possibly sildenafil being of benefit.
Group 3 PAH does not respond to conventional pulmonary hypertension therapies but oxygen will often be prescribed. Occasionally, Sildenafil will be trialled for 3 months.
Group 4 PAH (CTEPH) is the only type of PH that may be cured surgically (with pulmonary thrombo-endarterectomy) or with interventional balloon angioplasty. Riociguat or endothelin antagonists may be used if surgery is not an option or if there is an inadequate response to surgery.
Each treatment option is currently reimbursed on the pharmaceutical benefits scheme (PBS) if the there is significant breathlessness. However, the government will only subsidise one agent.
Applications to the government for medication scripts take 2-3 weeks to be approved and need to be reassessed and renewed every 6months.
Medications can only be prescribed via a recognised PAH prescribing clinician.
General measures for treatment of PAH include structured physical activity and lifestyle measures such as salt reduction, fluid management, smoking cessation, alcohol reduction, avoidance of amphetamines or weight loss medications.
Pregnancy with this condition can be high risk to the mother and foetus and so contraception is recommended.
Infection prevention is advised with annual influenza vaccines and 5 yearly pneumonia vaccines.
Oxygen therapy may be required at home or during airplane flights.
Anticoagulation for CTEPH and diuretics may be required.
The 2 commonest rheumatological conditions associated with pulmonary arterial hypertension (PAH) are scleroderma and systemic lupus erythematosis (SLE), also known as lupus. Many other connective tissue disorders (CTD) can be implicated as well.
Scleroderma literally translates into “hard skin” and is characterised by thickening of the skin. The symptoms of scleroderma vary and there are difference subtypes, but the main manifestations are:
- Thickening and hardening of the skin, especially of the fingers and face
- Raynaud’s phenomenon whereby the digits turn white, blue and then red, representing vasospasm in response to the cold. Not everyone with Raynaud’s has scleroderma, but most people with scleroderma have Raynaud’s and it is often the first symptom to appear
- Calcininosis representing calcium deposits under the skin
- Pain or stiffness in the joints or muscles
- Reflux or heartburn
- Shortness of breath or reduced ability to exercise from PAH or pulmonary fibrosis (lung scarring)
SLE is a systemic inflammatory condition with many manifestations including:
- Joint pain and/or swelling, especially in the hands or feet
- A photosensitive skin rash, often on the cheeks and nose of bridge – this is often referred to as a malar or 'butterfly" rash
- Mouth sores
- Blood abnormalities – low haemoglobin, white cells and/or platelets
- Kidney involvement
Both scleroderma and SLE are considered autoimmune conditions with no known causes. They develop from a combination of genetic factors and environmental triggers. A Rheumatologist will generally diagnose a CTD based on your clinical features and investigation results.
It is important to note that these rheumatological conditions are very variable and that no two patients are the same. Your Rheumatologist will identify what manifestations are present in the affected individual and tailor treatment accordingly, which may sometimes involve medications that suppress the immune system.
PAH medications are very expensive and highly regulated by the Government. They can only be prescribed by PAH designated hospitals and centres. A list of available centres can be found at:
Pulmonary Hypertension Society of Australia and New Zealand
The Thoracic Society of Australia and New Zealand (ANZCOTR)
The International Society for Heart & Lung Transplantation (ISHLT)
Lung Foundation Australia
St Vincents Hospital
Pulmonary Vascular Research Institute (PVRI)
Pulmonary Hypertension Association Australia (PHAA)