Is it okay to assume pulmonary hypertension (PH) and tailor treatment?

No, It Is Not Acceptable to Assume Pulmonary Hypertension and Tailor Treatment

Right heart catheterization (RHC) is mandatory for definitive diagnosis of pulmonary hypertension before initiating PAH-specific therapy, and treatment should never be based on assumption alone. 1

Why Definitive Diagnosis Is Essential

Hemodynamic Confirmation Required

• RHC remains the gold standard for confirming PH, requiring demonstration of mean pulmonary artery pressure ≥25 mmHg (older guidelines) or >20 mmHg (2024 update) 1, 2, 3
• The diagnosis must include measurement of pulmonary arterial wedge pressure (PAWP) and pulmonary vascular resistance (PVR) to distinguish between pre-capillary PH (PAWP ≤15 mmHg, PVR >2 Wood units) and post-capillary PH (PAWP >15 mmHg) 1, 3
• Echocardiography alone is insufficient for diagnosis—it serves only as a screening tool, not a diagnostic confirmation 1

Critical Distinction Between PH Groups

The classification of PH into five groups has profound treatment implications:

• Group 1 (Pulmonary Arterial Hypertension): PAH-specific drugs are indicated 1, 4
• Group 2 (Left Heart Disease): PAH-specific drug therapy is NOT recommended (Class III recommendation) 1
• Group 3 (Lung Disease): PAH-specific drug therapy is NOT recommended (Class III recommendation) 1
• Group 4 (CTEPH): Surgical pulmonary endarterectomy is the primary treatment, not medical therapy 1
• Group 5 (Unclear/Multifactorial): No RCTs support PAH-approved drugs; treatment targets underlying cause 1

Dangers of Empiric Treatment Without Diagnosis

Risk of Harm in Wrong PH Subtype

• Patients with pulmonary veno-occlusive disease (PVOD) can develop life-threatening pulmonary edema when started on PAH-specific vasodilators 1
• Patients with left heart disease or lung disease receiving PAH drugs may experience worsening outcomes, as these medications are contraindicated in these populations 1
• Conventional vasodilators like calcium channel blockers can impair gas exchange in lung disease by inhibiting hypoxic pulmonary vasoconstriction 1

Missed Treatable Causes

• CTEPH requires surgical intervention (pulmonary endarterectomy), not medical therapy as first-line treatment 1
• Delaying proper diagnosis means delaying potentially curative surgery for CTEPH patients 1
• Left heart disease and lung disease require optimization of the underlying condition, not PAH-specific drugs 1

The Proper Diagnostic Algorithm

Step 1: Screening with Echocardiography

• Echocardiography is recommended as the initial screening tool when PH is suspected 1, 2
• Tricuspid regurgitation velocity >3.4 m/s (corresponding to PA systolic pressure >50 mmHg) indicates likely PH and warrants further evaluation 2
• Look for right ventricular enlargement (RV/LV basal diameter ratio >1.0), septal flattening, and signs of RV dysfunction 2

Step 2: Determine Probability and Refer

• High probability cases (echocardiographic signs of likely PH with symptoms): RHC is recommended (Class I) 1
• Patients should be referred to a specialized PH center that follows at least 50 patients with PAH or CTEPH and receives at least two new referrals per month 1
• Fast-track referral is indicated if there are signs of severe pulmonary vascular disease or right heart failure 3

Step 3: Complete Diagnostic Workup

• Ventilation/perfusion lung scan is mandatory to exclude CTEPH 1
• High-resolution CT should be considered to assess for lung parenchymal disease 1
• Routine biochemistry, immunology, and thyroid function tests identify specific associated conditions 1
• RHC provides definitive hemodynamic diagnosis and guides appropriate therapy 1, 2

When Treatment Can Begin

• Only after RHC confirms Group 1 PAH should PAH-specific therapy be initiated 1
• Current first-line therapy consists of combination drug therapy targeting multiple biological pathways (e.g., ambrisentan plus tadalafil), which has improved 5-year survival from 34% to over 60% 4
• Approved therapies include prostacyclin pathway agonists, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors 5, 4, 6

Common Pitfalls to Avoid

• Never start PAH-specific drugs based on echocardiography alone—this can cause harm in Groups 2,3, and PVOD 1
• Do not assume all dyspnea with elevated PA pressures represents treatable PAH—most PH is due to left heart disease or lung disease 7, 8
• Recognize that physical examination has poor sensitivity for detecting moderate PH, particularly in obese patients 2
• Ensure PAWP measurement during RHC to distinguish pre-capillary from post-capillary PH, as this fundamentally changes management 1, 3