Pulmonary Hypertension: Diagnosis and Management
Diagnostic Confirmation with Right Heart Catheterization
Right heart catheterization is mandatory to confirm the diagnosis of pulmonary hypertension before initiating any treatment, and must be performed at expert centers due to technical complexity and potential complications. 1
When RHC is Required:
- Confirmation of PAH diagnosis (Group 1 PH): RHC is essential to document mean pulmonary artery pressure >20 mmHg, pulmonary artery wedge pressure ≤15 mmHg, and pulmonary vascular resistance >3 Wood units 1, 2
- Treatment decision support: Required before starting any PAH-specific therapy 1
- Congenital heart disease with shunts: Mandatory to determine operability and guide surgical correction decisions 1
- Pre-transplant evaluation: Required in Group 2 (left heart disease) or Group 3 (lung disease) patients being considered for organ transplantation 1
- Chronic thromboembolic PH (Group 4): Essential to confirm diagnosis and support treatment decisions 1
Key Hemodynamic Measurements:
- Mean pulmonary artery pressure, pulmonary artery wedge pressure, cardiac output, and calculated pulmonary vascular resistance 1, 3
- If PAWP is unreliable, left heart catheterization should be performed to measure left ventricular end-diastolic pressure 1
Vasoreactivity Testing: Strict Indications Only
Vasoreactivity testing is recommended ONLY in patients with idiopathic PAH, heritable PAH, and drug-induced PAH—it is explicitly contraindicated in all other forms of pulmonary hypertension. 1, 4
Who Should Undergo Testing:
- Eligible patients: IPAH, heritable PAH (HPAH), and PAH associated with anorexigen/drug use 1, 5
- Ineligible patients (Class III recommendation—do NOT test): Connective tissue disease-PAH, congenital heart disease-PAH, HIV-PAH, portopulmonary hypertension, pulmonary veno-occlusive disease, and all Group 2,3,4, and 5 PH 1, 4, 5
Testing Protocol:
- Preferred agent: Inhaled nitric oxide 1
- Alternative agents: Intravenous epoprostenol or adenosine 1
- May consider: Inhaled iloprost 1
- Never use: Oral or intravenous calcium channel blockers during acute testing 1, 5
Definition of Positive Response:
A positive vasoreactive response requires all three criteria:
- Reduction in mean PAP ≥10 mmHg 1, 3, 6
- Absolute mean PAP ≤40 mmHg 1, 3, 6
- Increased or unchanged cardiac output 1, 3, 6
Only ~10-15% of IPAH patients meet these criteria 1, 6
Calcium Channel Blocker Therapy: For Vasoreactive Patients Only
Calcium channel blockers should be initiated only in patients who demonstrate positive acute vasoreactivity testing, using high doses that far exceed those for systemic hypertension. 5
Drug Selection Based on Heart Rate:
- Resting HR <70-75 bpm: Start extended-release nifedipine (target 120-240 mg daily) or amlodipine (target up to 20 mg daily) 5
- Resting HR >75-80 bpm: Start diltiazem (target 240-720 mg daily) to counteract baseline tachycardia 5
Titration Strategy:
| Drug | Starting Dose | Target Dose | Titration |
|---|---|---|---|
| Nifedipine ER | 30 mg twice daily | 120-240 mg daily | Increase cautiously over weeks [5] |
| Amlodipine | 2.5 mg once daily | Up to 20 mg daily | Gradually increase to maximum tolerated [5] |
| Diltiazem | 60 mg three times daily | 240-720 mg daily | Progressively increase to maximum tolerated [5] |
Mandatory 3-4 Month Reassessment:
Repeat right heart catheterization at 3-4 months is non-negotiable to identify treatment failures. 1, 5
Adequate long-term response requires ALL of the following:
- WHO functional class I or II 5
- Marked hemodynamic improvement approaching near-normalization 5
- Mean PAP ideally <25 mmHg or substantial reduction 5
If any criterion is unmet, immediately add PAH-specific therapy. 5 Approximately 50% of acute responders fail to maintain long-term response and require escalation 5
Absolute Contraindications to CCB Use:
- No documented positive vasoreactivity testing 5
- PAH associated with connective tissue disease, HIV, portopulmonary hypertension, or pulmonary veno-occlusive disease—even if vasoreactive 5
- Right heart failure present 5
- Group 2,3,4, or 5 pulmonary hypertension 5
Critical Safety Monitoring:
- Blood pressure: Check at every dose escalation; reduce dose if systolic BP <90 mmHg 5
- Edema surveillance: Monitor weekly during titration for lower-extremity edema 5
- Never use immediate-release nifedipine 5
Fatal outcomes have been reported when CCBs are used in non-vasoreactive patients or doses are escalated inappropriately. 5
PAH-Specific Pharmacologic Therapies
Initial Treatment Strategy:
- Low or intermediate-risk, treatment-naïve patients: Start with approved monotherapy (endothelin receptor antagonists, phosphodiesterase-5 inhibitors, or prostacyclin analogs) 7
- Inadequate response to monotherapy: Add sequential combination therapy 7
Follow-Up Assessment Schedule:
- Every 3-6 months in stable patients: WHO functional class, 6-minute walk test, ECG, BNP/NT-proBNP, basic labs 7
- Treatment goal: Achieve and maintain low-risk profile (WHO class I-II, 6MWD >440m, BNP <50 ng/L) 7
Essential Diagnostic Workup Before Treatment
Screening and Initial Evaluation:
- Transthoracic echocardiography: First-line screening to estimate PA pressure, assess RV function, and identify left-sided abnormalities 7, 8
- Ventilation-perfusion scan: Mandatory in all PAH patients to exclude chronic thromboembolic PH (90-100% sensitivity for normal scan) 7
Additional Testing:
- Pulmonary function tests, chest CT, liver panel, complete blood count, thyroid function, HIV testing, and autoimmune serologies as clinically indicated 8
Surgical Interventions
Chronic Thromboembolic PH (Group 4):
- Pulmonary endarterectomy is the treatment of choice and must be performed at experienced centers using deep hypothermia circulatory arrest 7
Advanced Disease:
- Lung or heart-lung transplantation should be considered for WHO functional class III-IV patients refractory to maximal medical therapy 7
Common Pitfalls to Avoid
- Never perform vasoreactivity testing in congenital heart disease-PAH, connective tissue disease-PAH, or any Group 2-5 PH—it provides no useful information and exposes patients to unnecessary risk 1, 4
- Never start CCBs without documented positive vasoreactivity testing—this can cause life-threatening systemic hypotension, reflex tachycardia, and right ventricular ischemia 5
- Never omit the 3-4 month reassessment with repeat RHC in CCB-treated patients—failure to identify non-responders leads to delayed escalation and worse outcomes 5
- Never use CCBs empirically for symptom relief in PH—they are not general pulmonary vasodilators and are dangerous in non-vasoreactive patients 5