What is the current classification for mild, moderate, and severe Pulmonary Arterial Hypertension (PAH)?

Classification of Pulmonary Arterial Hypertension (PAH)

The current classification of PAH severity is primarily based on hemodynamic parameters and functional assessment rather than mild, moderate, and severe categories, with the World Health Organization (WHO) Functional Classification being the most widely used system for assessing disease severity and guiding treatment decisions. 1, 2

Hemodynamic Definition of PAH

PAH is defined as:

• Mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest 1
• More recently redefined in 2018 as mPAP >20 mmHg at rest 1
• Pulmonary capillary wedge pressure (PCWP) ≤15 mmHg 1, 2
• Pulmonary vascular resistance (PVR) >3 Wood units 1, 2

WHO Functional Classification for PAH Severity

The severity of PAH is primarily classified using the WHO Functional Classification system, which is modified from the New York Heart Association functional classification:

Class I (Mild)

• No limitation of physical activity
• Ordinary physical activity does not cause undue dyspnea, fatigue, chest pain, or near syncope
• Patients are comfortable at rest and with regular activities 1

Class II (Mild to Moderate)

• Slight limitation of physical activity
• Comfortable at rest
• Ordinary physical activity causes undue dyspnea, fatigue, chest pain, or near syncope 1

Class III (Moderate to Severe)

• Marked limitation of physical activity
• Comfortable at rest
• Less than ordinary activity causes undue dyspnea, fatigue, chest pain, or near syncope 1

Class IV (Severe)

• Unable to carry out any physical activity without symptoms
• Signs of right heart failure may be present
• Dyspnea and/or fatigue may be present even at rest
• Discomfort is increased by any physical activity 1

Clinical Classification of PAH

PAH is classified into five main groups based on etiology:

1. Group 1: Pulmonary arterial hypertension (including idiopathic, heritable, drug/toxin-induced, and associated PAH) 2
2. Group 2: PH due to left heart disease 2
3. Group 3: PH due to lung diseases and/or hypoxia 2
4. Group 4: Chronic thromboembolic pulmonary hypertension (CTEPH) 2
5. Group 5: PH with unclear and/or multifactorial mechanisms 2

Hemodynamic Classification

Based on the 2018 World Symposium on Pulmonary Hypertension, PH is further classified as:

1. Precapillary PH:

   • mPAP >20 mmHg
   • PAWP ≤15 mmHg
   • PVR ≥3 Wood units
   • Includes groups 1,3,4, and some from group 5 1

2. Isolated Postcapillary PH:

   • mPAP >20 mmHg
   • PAWP >15 mmHg
   • PVR <3 Wood units
   • Includes group 2 and some from group 5 1

3. Combined Pre- and Postcapillary PH:

   • mPAP >20 mmHg
   • PAWP >15 mmHg
   • PVR ≥3 Wood units
   • Includes group 2 and some from group 5 1

Important Clinical Considerations

• Right heart catheterization remains the gold standard for diagnosis and classification of PAH 2, 3
• Echocardiography is the primary non-invasive screening tool 2
• The WHO Functional Classification has significant prognostic value and guides treatment decisions 1, 4
• Regular assessment of functional class every 3-6 months is recommended to monitor disease progression 2

Pitfalls and Caveats

• The WHO Functional Classification has some subjectivity in assessment, particularly between Class II and III 4
• A patient-reported version (PH-FC-SR) has been developed to address limitations in the clinician-rated WHO-FC 4
• The definition of PAH has evolved over time, with the threshold for mPAP being lowered from ≥25 mmHg to >20 mmHg in 2018 1
• Functional classification alone may not fully capture disease severity; comprehensive assessment should include hemodynamic parameters, exercise capacity, and biomarkers 2

While terms like "mild," "moderate," and "severe" PAH are sometimes used clinically, the formal classification systems rely on the WHO Functional Classification and hemodynamic parameters rather than these descriptive terms.