Question
A 29-year-old woman comes to clinic with gradually worsening breathlessness on exertion over several months. She has no significant past illness, does not smoke, and her family history is unremarkable. Routine investigations are normal. Right heart catheterisation shows a mean pulmonary artery pressure of 32 mmHg. During vasoreactivity testing using inhaled nitric oxide, there is a marked fall in pulmonary artery pressure.
What is the most appropriate initial treatment?
a. Start an endothelin receptor blocker such as ambrisentan
b. Begin inhaled prostacyclin therapy
c. Initiate high-dose calcium channel blocker therapy (e.g., nifedipine)
d. Refer immediately for lung transplantation
e. Start a phosphodiesterase-5 inhibitor such as tadalafil
Answer
Initiate high-dose calcium channel blocker therapy (e.g., nifedipine)
Detailed Explanation
This patient has pulmonary arterial hypertension (PAH) confirmed by:
- Mean pulmonary artery pressure > 20 mmHg (here 32 mmHg)
The critical decision point in PAH management is acute vasodilator testing.
Positive vasoreactivity test (key concept)
- Defined as a significant fall in mean PAP with vasodilator (e.g., nitric oxide)
- Seen in a small subset (~10%) of patients
- Indicates preserved vasodilatory capacity
👉 These patients respond dramatically to high-dose calcium channel blockers (CCBs)
Why nifedipine (CCB)?
- Causes pulmonary vasodilation
- Improves survival in responders
- Only used if vasoreactivity test is positive
Why other options are wrong
- Endothelin receptor antagonists (e.g., ambrisentan)
→ Used when vasoreactivity test is negative - Prostacyclin analogues (e.g., iloprost)
→ Reserved for non-responders or severe disease - PDE-5 inhibitors (e.g., sildenafil/tadalafil)
→ Also for vasoreactivity-negative patients - Transplantation
→ Only in advanced disease refractory to therapy
Cheat Sheet (Exam Gold)
Pulmonary Arterial Hypertension (PAH)
- Definition: Mean PAP ≥ 20 mmHg
- Key symptom: Progressive exertional dyspnoea
Stepwise Management
- Confirm diagnosis (right heart cath)
- Perform vasoreactivity testing
If POSITIVE →
➡️ High-dose CCB (nifedipine, amlodipine)
If NEGATIVE →
➡️ Endothelin receptor antagonists (bosentan, ambrisentan)
➡️ PDE-5 inhibitors (sildenafil)
➡️ Prostacyclin analogues (iloprost)
Advanced disease →
➡️ Lung/heart-lung transplant
Flash Cards
Q1. What defines PAH?
A: Mean pulmonary artery pressure ≥ 20 mmHg
Q2. What is the key test guiding PAH treatment?
A: Acute vasodilator (vasoreactivity) testing
Q3. Best treatment if vasoreactivity test is positive?
A: High-dose calcium channel blockers
Q4. Drugs used if vasoreactivity test is negative?
A: Endothelin antagonists, PDE-5 inhibitors, prostacyclins
Q5. When is transplant considered?
A: Progressive disease despite optimal therapy
MCQs (High Difficulty)
MCQ 1
A patient with idiopathic PAH undergoes vasodilator testing and shows a fall in mean PAP by 12 mmHg to below 40 mmHg. What is the best next step?
a. Start sildenafil
b. Start bosentan
c. Begin nifedipine
d. Refer for transplant
e. Start iloprost
Answer: c
Explanation: Positive vasoreactivity → CCB is first-line.
MCQ 2
Which of the following is TRUE regarding vasoreactivity testing in PAH?
a. Most patients show a positive response
b. It is used to diagnose PAH
c. It determines suitability for CCB therapy
d. It is only done in severe disease
e. It replaces right heart catheterisation
Answer: c
Explanation: Only ~10% respond; it guides therapy, not diagnosis.
MCQ 3
Which of the following patients is LEAST likely to benefit from calcium channel blockers?
a. Idiopathic PAH with positive vasoreactivity
b. Drug-induced PAH with vasodilator response
c. PAH with negative vasoreactivity test
d. Early-stage PAH with nitric oxide response
e. Familial PAH with pressure drop on testing
Answer: c
Explanation: Negative test → CCB ineffective.
MCQ 4
Which drug class primarily blocks endothelin-mediated vasoconstriction in PAH?
a. Prostacyclin analogues
b. Calcium channel blockers
c. PDE-5 inhibitors
d. Endothelin receptor antagonists
e. ACE inhibitors
Answer: d
Explanation: Endothelin antagonists directly counter vasoconstriction.
MCQ 5 (False question)
Which of the following statements is FALSE regarding PAH?
a. Mean PAP ≥ 20 mmHg defines PAH
b. Most patients respond to vasodilator testing
c. Nitric oxide is used in vasoreactivity testing
d. CCBs are used only in responders
e. Transplant is considered in refractory cases
Answer: b
Explanation: Only a minority (~10%) respond.
MCQ 6
A patient with PAH has failed CCB therapy and remains symptomatic. What is the next best option?
a. Stop treatment
b. Start endothelin receptor antagonist
c. Immediate transplant
d. Give diuretics only
e. Beta-blockers
Answer: b
Explanation: Escalate to targeted PAH therapy.
Summary for Quick Exam Revision
Pulmonary arterial hypertension is defined by a mean pulmonary artery pressure of at least 20 mmHg on right heart catheterisation and typically presents with progressive exertional dyspnoea. The cornerstone of management is acute vasoreactivity testing, usually performed with inhaled nitric oxide, to identify patients who retain pulmonary vasodilatory capacity. A small subset of patients who demonstrate a positive response should be treated with high-dose calcium channel blockers such as nifedipine, which can significantly improve outcomes. In contrast, the majority of patients who do not respond require alternative targeted therapies, including endothelin receptor antagonists, phosphodiesterase-5 inhibitors, or prostacyclin analogues. Advanced or refractory cases may require lung or heart-lung transplantation. Thus, the vasoreactivity test is the pivotal step that determines first-line therapy and prognostic stratification in PAH.