How is acute vasodilator testing performed during right‑heart catheterisation for suspected pulmonary hypertension, and what criteria define a positive versus a negative response?

Acute Vasodilator Testing During Right Heart Catheterization

Acute vasodilator testing should be performed using inhaled nitric oxide or intravenous epoprostenol in patients with idiopathic, heritable, or drug-induced pulmonary arterial hypertension to identify the small subset (~10-15%) who can be safely treated with high-dose calcium channel blockers 1.

Who Should Undergo Testing

Vasodilator testing is only indicated for:

• Idiopathic PAH (IPAH)
• Heritable PAH (HPAH)
• Drug-induced PAH

Testing is NOT recommended for other PAH subtypes or PH groups 2,3,4, or 5, as positive responses are extremely rare and clinically irrelevant in these populations 1, 2.

How the Test is Performed

The procedure must be conducted at expert centers due to technical demands and potential complications 1:

Preferred Vasodilator Agents (in order of recommendation):

1. Inhaled nitric oxide (Class I recommendation) 1
2. Intravenous epoprostenol (Class I alternative) 1
3. Adenosine (Class IIa consideration) 1
4. Inhaled iloprost (Class IIb consideration) 1

Critical caveat: Oral or intravenous calcium channel blockers should NOT be used for acute testing 1.

Defining a Positive Response

A positive vasodilator test requires ALL three criteria 1:

1. Mean pulmonary artery pressure (mPAP) decreases by ≥10 mmHg
2. Absolute mPAP reaches ≤40 mmHg
3. Cardiac output increases or remains unchanged (does not decrease)

This stringent definition (Sitbon criteria) identifies approximately 10-15% of IPAH patients 2 and predicts those most likely to benefit from calcium channel blocker therapy.

Clinical Implications and Long-Term Response

The acute positive response does not guarantee long-term success. Recent high-quality data from 2024 reveals important nuances 3:

• Among acute responders treated with CCBs, only 54.3% maintained long-term response at 12 months
• Long-term responders had 98.5% five-year survival versus 73.0% in non-responders
• At 12-month follow-up, only 53.2% remained on CCB monotherapy; others required additional PAH therapies or CCB discontinuation

Long-term response criteria (assessed at 12 months):

• Alive on unchanged initial CCB therapy (with or without other PAH drugs)
• WHO functional class I/II and/or low ESC/ERS risk status

Predictors of Sustained Response

Beyond meeting acute vasoreactivity criteria, additional factors correlate with long-term success 3:

• Pulmonary artery compliance at time of testing
• Low-risk status at early follow-up
• Low NT-proBNP levels at early follow-up
• Younger age at diagnosis 4

Critical Pitfalls to Avoid

1. Inadequate follow-up: Comprehensive reassessment during early follow-up (within first year) is mandatory, as 50% may lose vasoreactivity 3, 5

2. Undertesting: Contemporary registry data shows VdT is performed in only 22% of appropriate candidates 4, representing a significant missed opportunity given the excellent survival in true responders

3. Testing inappropriate patients: Do not perform VdT in PAH associated with connective tissue disease, congenital heart disease, portal hypertension, or HIV, as positive responses are exceedingly rare 1, 2

4. Risk of pulmonary hypertension crisis: Younger age, general anesthesia, crisis history, and poor cardiac function increase complication risk during catheterization 6

5. Misinterpreting intermediate-risk patients: Those with intermediate-high risk criteria at baseline are more likely to have negative tests or lose vasoreactivity during follow-up 5

Practical Testing Algorithm

For patients with suspected IPAH/HPAH/DPAH undergoing diagnostic RHC:

1. Obtain baseline hemodynamics (mPAP, PAWP, cardiac output, PVR)
2. Administer inhaled nitric oxide (first choice) or IV epoprostenol
3. Measure hemodynamics after steady-state achieved
4. Apply strict Sitbon criteria for positive response
5. If positive: initiate high-dose CCB therapy
6. Mandatory reassessment at 3-6 months with functional class, 6-minute walk, NT-proBNP, and risk stratification
7. If deterioration or intermediate-high risk features: add PAH-specific therapy or discontinue CCB

The heterogeneity within vasoresponders emphasizes that acute testing alone is insufficient—ongoing vigilance with comprehensive early follow-up determines true long-term responders who achieve the exceptional survival outcomes that justify this testing approach 3.