WHO Functional Classification of Pulmonary Arterial Hypertension
The WHO Functional Classification of PAH categorizes patients into four classes based on symptom severity and physical activity limitations, which directly correlates with morbidity, mortality, and quality of life outcomes. 1
The Four WHO Functional Classes
Class I: Patients with pulmonary hypertension but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain, or near syncope. 1
Class II: Patients with pulmonary hypertension resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain, or near syncope. 1
Class III: Patients with pulmonary hypertension resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain, or near syncope. 1
Class IV: Patients with pulmonary hypertension with inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity. 1
Clinical Significance and Prognostic Value
The WHO-FC is a critical tool for:
Treatment decisions: Functional class directly influences medication choices and treatment intensity 1, 2
Prognostic assessment: Patients in lower functional classes (I-II) have significantly better survival rates than those in higher classes (III-IV) 3
Disease monitoring: Changes in functional class over time provide valuable information about disease progression or treatment response 1, 3
Relationship to Mortality and Outcomes
Patients who improve from FC III to FC I/II have significantly better 3-year survival (84% ± 2%) compared to those who remain at FC III (66% ± 2%) or worsen to FC IV (29% ± 6%) 3
WHO-FC is considered one of the most important determinants of prognosis in PAH patients, with Class I-II associated with better outcomes than Class III-IV 1, 4
The functional classification is used as an eligibility criterion for specific PAH therapies, such as epoprostenol, which is indicated predominantly for patients with NYHA Functional Class III-IV symptoms 2
Clinical Application and Assessment
WHO-FC should be assessed at baseline, every 3-6 months during stable disease, at initiation or changes in therapy, and in case of clinical worsening 1
The classification is subjective and may have limitations, particularly in distinguishing between Class II and Class III 5
A patient-reported version called the Pulmonary Hypertension Functional Classification Self-Report (PH-FC-SR) has been developed to complement clinician assessment 5
Common Pitfalls and Caveats
WHO-FC assessment can be subjective and varies between providers 5
Patients may underreport symptoms or overestimate their functional capacity 5
The distinction between Class II and Class III can be particularly challenging and requires careful clinical assessment 5
Functional class should not be used in isolation but combined with other prognostic parameters such as exercise capacity (6MWT), biomarkers (BNP/NT-proBNP), and hemodynamic measurements for comprehensive patient evaluation 1