What are the diagnostic criteria for Pulmonary Arterial Hypertension (PAH)?

Diagnostic Criteria for Pulmonary Arterial Hypertension (PAH)

PAH is definitively diagnosed by right heart catheterization demonstrating mean pulmonary artery pressure (mPAP) >25 mm Hg at rest, pulmonary artery wedge pressure (PAWP) ≤15 mm Hg, and pulmonary vascular resistance (PVR) >3 Wood units. 1, 2

Hemodynamic Requirements

The diagnosis of PAH requires all three of the following hemodynamic criteria measured by right heart catheterization:

• mPAP >25 mm Hg at rest - This threshold defines pulmonary hypertension broadly 1
• PAWP ≤15 mm Hg - This distinguishes pre-capillary from post-capillary pulmonary hypertension and excludes left heart disease as the primary cause 1
• PVR >3 Wood units - This is the critical criterion that confirms true pulmonary vascular disease rather than passive elevation from high cardiac output states 1, 2

Note: Recent evidence suggests a lower mPAP threshold of >20 mm Hg may be adopted in future guidelines, though the >25 mm Hg threshold remains the current standard in most clinical practice guidelines 3, 4.

Why PVR is Essential

PVR is a more robust diagnostic criterion than mPAP alone because it reflects both transpulmonary gradient and cardiac output, and is only elevated when vascular obstruction occurs within the pre-capillary pulmonary circulation. 1, 2

• PVR distinguishes passive PH (elevated mPAP with normal PVR) from true pulmonary vascular disease (elevated mPAP with elevated PVR) 1, 2
• Conditions like anemia, pregnancy, sepsis, or thyrotoxicosis can elevate mPAP through high cardiac output alone, but PVR remains normal 1
• A subset of patients with left heart disease may have disproportionately elevated PVR >3 Wood units with transpulmonary gradient >20 mm Hg, indicating superimposed pulmonary vascular disease 1, 2

Mandatory Invasive Confirmation

Right heart catheterization is absolutely required to confirm PAH and must not be replaced by echocardiographic estimates alone. 1

• Doppler echocardiography serves as the initial screening tool but is imprecise in determining actual pressures compared to invasive evaluation 1
• Echocardiography has limited positive predictive value and should never be used to make treatment decisions without catheterization confirmation 1, 2
• Right heart catheterization is required both to establish the diagnosis and to guide therapy 1

Diagnostic Algorithm

Step 1: Clinical Suspicion

Look for these specific presenting features:

• Dyspnea on exertion and fatigue (most common, though nonspecific) 1, 5
• Syncope, chest pain, or peripheral edema 1
• Risk factors: family history, connective tissue disease, HIV, portal hypertension, congenital heart disease, drug/toxin exposure, or thromboembolic disease 1

Step 2: Initial Screening

• Perform Doppler echocardiography as the first-line noninvasive screening test 1
• Echocardiography detects pulmonary hypertension and assesses right ventricular structure/function 1

Step 3: Exclude Other Causes

Before confirming PAH, you must rule out other forms of pulmonary hypertension:

• Ventilation-perfusion (V/Q) scanning is mandatory to exclude chronic thromboembolic pulmonary hypertension (CTEPH); a normal V/Q scan effectively excludes CTEPH 1
• Test for connective tissue disease and HIV infection in all patients with unexplained PAH 1
• Perform pulmonary function tests and arterial blood gases to exclude lung parenchymal disease 1
• Assess for left heart disease through echocardiography and clinical evaluation 1

Step 4: Invasive Confirmation

• Proceed to right heart catheterization to confirm hemodynamic criteria and establish severity 1
• Calculate PVR as: (mPAP - PAWP) / cardiac output 2

Critical Pitfalls to Avoid

Do not treat based on echocardiography alone - The positive predictive value of echocardiographic estimates is insufficient for treatment decisions, particularly in general cardiology populations where left heart disease is far more common than true PAH 1, 2

Do not use calcium channel blockers empirically - These should only be used after demonstrating acute vasoreactivity during right heart catheterization (defined as fall in mPAP ≥10 mm Hg to ≤40 mm Hg with increased or unchanged cardiac output) 1

PAH remains a diagnosis of exclusion - After excluding lung disease, thromboembolic disease, left ventricular disease, and valvular disease, the combination of mPAP >25 mm Hg and PVR >3 Wood units makes PAH the most likely diagnosis 1