What is Pulmonary Hypertension?
Pulmonary hypertension (PH) is a hemodynamic and pathophysiological condition defined as an increase in mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest as measured by right heart catheterization. 1, 2, 3
Core Definition and Diagnostic Threshold
- The established diagnostic threshold is mPAP ≥25 mmHg at rest, which has been used to select patients in all randomized controlled trials and registries 1, 2
- Normal mean pulmonary arterial pressure at rest is 14 ± 3 mmHg, with an upper limit of normal of 20 mmHg 1
- Recent guidelines propose lowering the threshold to >20 mmHg, though the 25 mmHg cutoff remains the widely referenced standard in clinical practice 3, 4
- Right heart catheterization remains the gold standard for confirming the diagnosis 2, 3
Important caveat: The definition of PH on exercise (previously defined as mPAP >30 mmHg) is no longer supported by published data and should not be used, as healthy individuals can reach much higher values during exercise 1, 2, 3
Hemodynamic Classifications
PH is further categorized based on specific hemodynamic parameters that guide treatment decisions:
Pre-capillary PH
- mPAP ≥25 mmHg 1, 2
- Pulmonary wedge pressure (PWP) ≤15 mmHg 1, 2, 5
- Pulmonary vascular resistance (PVR) ≥3 Wood units 2, 5
- Cardiac output normal or reduced 1
Post-capillary PH
Combined Pre- and Post-capillary PH
Clinical Classification System
PH encompasses multiple clinical conditions organized into five major groups based on shared pathophysiology, hemodynamic characteristics, and treatment approaches: 1, 2, 3, 6
Group 1: Pulmonary Arterial Hypertension (PAH)
- Characterized by pre-capillary PH with PVR >3 Wood units due to remodeling of small pulmonary arteries (<500 μm) 3, 6
- Includes:
Group 2: PH Due to Left Heart Disease
- The most common form of PH 3
- Characterized by post-capillary PH with PAWP >15 mmHg due to backward transmission of elevated left atrial pressure 3, 5
- Includes left ventricular systolic dysfunction, diastolic dysfunction, and valvular disease 1, 2, 3
Group 3: PH Due to Lung Diseases and/or Hypoxia
- Results from alveolar hypoxia causing pulmonary vasoconstriction and vascular remodeling 5
- Includes chronic obstructive pulmonary disease, interstitial lung disease, sleep-disordered breathing, and alveolar hypoventilation disorders 3, 6
Group 4: Chronic Thromboembolic PH (CTEPH)
Group 5: PH with Unclear and/or Multifactorial Mechanisms
Clinical Significance and Natural History
- Without treatment, PH leads to increased pulmonary vascular resistance, progressive right ventricular hypertrophy, right heart failure, and ultimately death 1, 4, 7
- The median life expectancy from diagnosis in patients with idiopathic PAH before disease-specific therapy was only 2.8 years 2, 5
- At least 1% of the world's population is affected by some form of PH 3, 4
- The most common symptom is dyspnea, though symptoms are nonspecific and may include fatigue, weakness, angina, peripheral edema, hepatomegaly, ascites, and syncope 1, 4
Key Distinction: PH vs PAH
Pulmonary hypertension is a broad hemodynamic term, while pulmonary arterial hypertension (PAH) is a specific clinical entity: 1