Pulmonary hypertension (PH) occurs when there is increase pressure in the pulmonary arteries. An increase in pulmonary artery pressure leads to an increased afterload within the right side of the heart as well as back pressure through the systemic venous circuit.
Pathophysiology
The mean pulmonary arterial pressure is approximately 15mmHg. The mechanisms that may lead to pulmonary hypertension include:
- Increased pulmonary vasculature resistance - pathological vasoconstriction, smooth muscle hypertrophy and chronic inflammation leads to vascular remodelling which causes greater resistance and pressure through the arteries.
- Increased pulmonary venous pressure - left sided heart disease leads to elevated pressure in the pulmonary veins which leads to damage of the alveolar-capillary wall and can lead to oedema in the lungs. It also causes increased pressure in the arterial system as well.
- Increased pulmonary venous flow due to congenital heart diseases - ASDs, VSDs, and PDA can all lead to increased pulmonary venous blood flow as well which can then cause vascular obstruction and back flow of blood and resultant pulmonary hypertension.
PH may be a result of the following types of disease:
- Parenchymal lung diseases - COPD, asthma, interstitial lung disease, bronchiectasis, cystic fibrosis.
- Pulmonary vascular diseases - idiopathic pulmonary hypertension, pulmonary vasculitis, PE, portal hypertension.
- Hypoventilation - sleep apnoea, kyphosis/scoliosis, neuromuscular conditions.
- Left heart diseases - mitral stenosis, mitral regurgitation, left-sided heart failure.
🔢 Classification
There are 5 groups of PH according to the WHO Classification of Pulmonary Hypertension:
- Group 1: Pulmonary arterial hypertension (PAH)
- Idiopathic PAH - we will discuss this in more detail.
- Drug/toxin induced PAH as seen in drugs such as cocaine or buprenorphine.
- Primary pulmonary hypertension due to connective tissue disorders, HIV, portal hypertension, congenital heart disease, schistosomiasis, SLE.
- Group 2: Pulmonary hypertension due to left heart disease
- LVSD
- LVDD
- Mitral stenosis/regurgitation
- Cardiomyopathy
- Group 3: Pulmonary hypertension due to lung diseases and/or hypoxia
- COPD
- Interstitial lung disease
- OSA
- Group 4: Chronic thromboembolic pulmonary hypertension - for example in pulmonary embolism.
- Group 5: Unknown/miscellaneous causes of pulmonary hypertension
- Haematological disorders
- Systemic disorders - such as sarcoidosis
- Metabolic disorders such as glycogen storage disease
Idiopathic pulmonary arterial hypertension (IPAH) is when there is pulmonary hypertension that occurs with no underlying causation and not secondary to any disease. It may include some hereditary factors which damage the pulmonary vasculature.
⚠️ Risk factors
- Family history
- Female sex
- 20-50 years old
- BMPR2 mutations
- Appetite suppressant medication - aminorex, fenfluramine, dexenfluramine, benfluorex.
😷 Presentation
The main symptom of pulmonary hypertension is shortness of breath.
Other signs and symptoms may include:
- Syncope - as the cardiac output falls we get near syncopes and syncope. These are more concerning symptoms.
- Tachycardia
- Raised JVP
- Hepatomegaly - due to obstructive vasculopathy which leads to portal hypertension.
- Peripheral oedema
- Accentuated P2 to second heart sound - as there is delayed closure of the pulmonary valve.
- Tricuspid regurgitation murmur - heard at the left sternal border.
🔍 Investigations
☝️ Note: these investigations are not specific to IPAH only and include investigating other causes of pulmonary hypertension, especially heart diseases.
- CXR - an enlarged pulmonary artery is seen in 90% of cases, as well as enlarged hilar vessels. We may also see evidence of other disease if it is secondary to other disease, for example, we may see right ventricular hypertrophy.
- Transthoracic Doppler echocardiography
- Right ventricular hypertrophy - seen as large R waves, on the right-sided precordial leads as well as S waves on the left-sided precordial leads.
- Right axis deviation
- Right bundle branch block
- P-pulmonale
Other investigations we may opt to do include:
- NT-proBNP - elevations indicate right heart failure.
🧰 Management
The 5-year survival for pulmonary hypertension is quite poor, at 30-40%.
Management depends on patients being responsive/unresponsive to vasoreactivity testing. A positive response is defined as fall in mean pulmonary artery pressure of 10-40mmHg.
- Responsive - should be started on a CCB.
- If HR <100bpm: nifedipine or amlodipine
- If HR >100bpm: diltiazem (verapamil should not be used due to its negative inotropic effect).
- Unresponsive or CCB contraindicated - should be started on an endothelin receptor antagonist (-ntan) or PDE-5 inhbitor (-fil) if low-intermediate risk. If at high risk they should be given IV prostanoids.
- Low-intermediate risk: macitentan/ambrisentan/bosentan (all are endothelin receptor antagonists) ± sildenafil/tadalafil (PDE-5 inhibitors).
- High risk: IV epoprostenol
Secondary pulmonary hypertension is managed by treatment of the underlying cause.
We should also provide supportive treatment for symptoms, such as respiratory failure, arrhythmias, oedema etc.