What is Pulmonary Hypertension?

Pulmonary hypertension (PH) is a disease in which the blood pressure in the arteries of the lungs is higher than normal. This forces the heart, especially the right side, to work harder to pump blood to the lungs.

Over time, this increased workload can lead to shortness of breath, severe fatigue, and, if left untreated, significant damage to the heart and other organs. Although PH cannot always be cured, effective treatments are now available that improve symptoms, slow disease progression, and allow many people to live more active lives.

Currently, PH is defined as a mean pulmonary artery pressure greater than 20 mmHg at rest, measured using a procedure called right heart catheterization [1].

Most Common Symptoms

Pulmonary hypertension may begin silently and progress slowly. The most common symptoms include:

  • Shortness of breath (dyspnea), initially with exertion and later even at rest
  • Persistent tiredness or fatigue
  • Chest pain or pressure
  • Dizziness or fainting
  • Swelling of the legs, ankles or abdomen (a sign of right heart failure)
  • Palpitations (rapid or irregular heartbeats)

These symptoms can be confused with those of other more common conditions, which is why early medical evaluation is essential.

How is It Diagnosed?

The diagnosis of PH usually begins with a clinical evaluation (medical history and physical examination) when persistent symptoms raise suspicion. Further testing may include:

  • Echocardiogram
  • A noninvasive ultrasound test that estimates pulmonary artery pressures and evaluates heart function.
  • Right heart catheterization
  • The gold standard test. It directly measures pressures in the pulmonary arteries and confirms the diagnosis [1, 6].

Additional tests

  • Chest X-ray
  • Computed Tomography (CT) scan
  • Pulmonary function tests
  • Pulse oximetry or arterial blood gas analysis
  • Six-minute walk test

These tests help identify the underlying causes of PH and guide planning of the most appropriate treatment [6].

Why Does It Occur?

Causes and Classification

Pulmonary hypertension is not a single disease, but rather a group of disorders with different underlying causes. It is classified into five groups based on the origin of the condition [1,7].

Group 1: Pulmonary Arterial Hypertension (PAH)

In this group, the problem lies directly within the small pulmonary arteries, which become thicker, stiffer, and narrower. This markedly increases pressure within these vessels, even when there is no other significant underlying heart or lung disease.

Common types of PAH include:

  • Idiopathic PAH: no clear cause is identified
  • Heritable PAH: related to genetic mutations that can be inherited within a family.
  • PAH associated with other diseases: including connective tissue diseases (e.g., scleroderma or lupus), HIV infection, liver disease, or congenital heart disease.
  • PAH associated with exposure to certain drugs or toxins, including specific weight-loss medications.

Group 1 has specific treatments that directly target pulmonary arteries.

Group 2: PH due to left heart disease

This form of PH occurs when the left side of the heart does not pump efficiently, for example, due to heart failure or valvular heart disease. Blood backs up into the lungs, increasing pressure in the pulmonary circulation [9].

The priority in this group is to treat the underlying heart disease (cardiac medications, valve repair, etc.) rather than using PH-specific medications [9].

Group 3: PH due to lung diseases or hypoxia

This form of PH develops due to chronic lung disease or long-term low oxygen levels in the blood.

Common causes include:

  • Chronic Obstructive Pulmonary Disease (COPD)
  • Pulmonary fibrosis
  • Moderate to severe untreated sleep apnea
  • Interstitial lung diseases
  • Living or working for long periods at high altitude

The main priority is treatment of the underlying lung disease and ensure adequate oxygenation. In carefully selected cases, PAH-specific medications may be used; however, their benefit has not been clearly demonstrated in many patients and they may be harmful, so their use should always be supervised by experienced specialists [1,7].

Group 4: Chronic thromboembolic pulmonary hypertension

This type is caused by old blood clots that do not fully dissolve and obstruct the pulmonary arteries.

Treatment options include surgery (pulmonary endarterectomy), balloon pulmonary angioplasty, or anticoagulant and targeted medications [9].

Group 5: PH with multifactorial or unclear mechanisms

This group includes cases associated with multiple concurrent causes or less common conditions (e.g., hematologic disorders, selected metabolic diseases, or splenic abnormalities). Treatment is individualized based on the underlying disease [9].

Available Treatments

Treatment depends on the type of PH, its severity, and its underlying cause. The goal is to improve symptoms, exercise capacity, and survival, while maintaining patients at the lowest possible risk level [1,2].

1. General Treatments

  • Oxygen therapy (when oxygen levels are low)
  • Diuretics
  • Pulmonary rehabilitation
  • Supervised physical activity
  • Vaccinations and infection control

2. PAH-Specific Treatments (Group 1)

These medications aim to dilate the pulmonary vessels and improve blood flow:

  • Calcium channel blockers (at high doses)
  • These agents are effective only in a small subset of patients with PAH who demonstrate a positive acute vasoreactivity test during right heart catheterization.
  • In such cases, medications such as nifedipine, diltiazem, or amlodipine may relax the pulmonary arteries and improve symptoms.
  • They should not be used in patients without documented vasoreactivity, as they may be ineffective or potentially harmful.
  • Endothelin receptor antagonists (ERAs)
  • Endothelin is a potent vasoconstrictor; these medications block its effects and promote pulmonary arterial vasodilation.
  • They are administered orally and have been shown to improve exercise capacity and delay disease progression [10].
  • Examples include bosentan, ambrisentan, and macitentan.
  • Phosphodiesterase type 5 (PDE-5) inhibitors and soluble guanylate cyclase (sGC) stimulators
  • These agents promote pulmonary vasodilation and improve blood flow.
  • They are administered orally and are frequently used in combination with an endothelin receptor antagonist from the initiation of therapy.
  • Examples include sildenafil and tadalafil.
  • Prostacyclin pathway agents
  • Prostacyclin is an endogenous substance that dilates pulmonary arteries, inhibits platelet aggregation, and limits vascular remodeling.
  • Available formulations include intravenous, subcutaneous, inhaled, and oral therapies. These agents are primarily used in patients with moderate to severe PAH or when oral therapies are insufficient. Examples include epoprostenol, treprostinil, iloprost, and selexipag.

Early Combination Therapy and Risk-based Approach

Current guidelines recommend initiating combination therapy rather than monotherapy, as this strategy improves outcomes and delays disease progression [1,2].

Patient risk (low, intermediate, or high) is reassessed periodically, and treatment is adjusted based on clinical response.

Novel Therapies: Sotatercept

Sotatercept is an innovative agent that targets a novel signaling pathway (TGF-β), distinct from traditional PAH therapies.

Recent clinical trials (STELLAR, SOTERIA) have demonstrated the following benefits [3,4,5]:

  • Improved exercise capacity
  • Reduced cardiac workload
  • Improved quality of life
  • Reduced risk of clinical worsening

3. Treatment in Group 3 (PH Due to Lung Disease)

In Group 3, the main goal of treatment is to improve the lung disease and ensure the body gets enough oxygen.

Key measures include:

  • Optimal treatment of the underlying respiratory disease (e.g., inhaled therapies and pulmonary rehabilitation in COPD, antifibrotic therapy in selected forms of pulmonary fibrosis, CPAP or BiPAP in sleep apnea).
  • Oxygen therapy is recommended for patients with persistently low oxygen saturation; it helps reduce pulmonary artery pressure and improves exercise tolerance.
  • Influenza and pneumococcal vaccination, smoking cessation, and avoidance of environmental or occupational exposures that may further damage the lungs.

PAH-specific medications, such as endothelin receptor antagonists or PDE-5 inhibitors, are not routinely recommended in Group 3 PH. Their use is limited to very selected cases and should be supervised by expert centers, as clinical studies have shown variable results.

4. Treatment of Chronic Thromboembolic PH (Group 4)

  • Surgical removal of thromboembolic material (when feasible)
  • Balloon pulmonary angioplasty
  • Targeted medical therapy when surgery is not an option

Looking to the Future

Pulmonary hypertension is a serious disease; however, far more treatment options are available today than in the past.

With early diagnosis, care at specialized centers, and appropriate therapy, many patients can live longer and enjoy a better quality of life.

Registry

Pulmonary Hypertension Association Registry (PHAR) (Global)

Important Safety Notice

This information is for educational purposes only and does NOT replace professional medical consultation.

  • Each case of pulmonary hypertension is unique.
  • Only your medical specialist can determine which specific tests you need.
  • The diagnostic process may vary depending on your symptoms and medical history.
  • ALWAYS consult your healthcare team regarding your individual situation.

Your doctor has the final authority regarding your diagnosis and the required tests.

If you experience emergency symptoms (severe chest pain, extreme shortness of breath, or fainting), seek immediate medical attention.

References:

  1. Humbert M, et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. European Respiratory Journal. 2022.
  2. Dardi F, et al. World Symposium on Pulmonary Hypertension 2024: Updated treatment algorithm. European Respiratory Journal. 2024.
  3. McLaughlin VV, et al. Sotatercept for pulmonary arterial hypertension. New England Journal of Medicine. 2024.
  4. Souza R, Badesch DB, Ghofrani HA, et al. STELLAR trial. European Respiratory Journal. 2023.
  5. Sitbon O, Boucly A, Weatherald J, et al. Drugs targeting novel pathways in PAH. European Respiratory Journal. 2025.
  6. National Heart, Lung, and Blood Institute (NHLBI). Diagnóstico de hipertensión pulmonar.
  7. Recent advances in pulmonary arterial hypertension. National Library of Medicine. PMC11533989, 2024.
  8. European Lung Foundation. PH Lay Guidelines (ES).