• Idiopathic PAH
• Familial PAH
• Secondary PAH (connective tissue, congenital, portal HTN, portal HTN, HIV, Drugs/toxins)
• Pulmonary HTN with left heart disease, lung diseases, chronic thrombotic/embolic diseases

Prostacyclin

NO

Endothelin-1

Thromboxane

Von Willebrand

Autoantibodies

Pro-Inflammatory Cytokines

Symptoms

• Dyspnea
• Fatigue
• Exercise intolerance
• Weakness
• Chest pain
• Syncope

Signs

• Pulmonary regurgitation
• Tricuspid regurgitation
• JVD
• HJR
• Peripheral edema

Mean Pulmonary Artery Pressure (mPAP) > 25 mmHg at rest

+

Pulmonary Capillary Wedge Pressure (PCWP) < 15 mmHg

+

Pulmonary Vascular Resistance (PVR) > 3 wood units

WHO Classification

Class I -- No limitations of usual physical activity

Class II -- Mild limitation; strenuous normal daily activity causes increased symptoms

Class III -- Marked limitation; less than normal physical activity increases symptoms

Class IV -- Unable to perform any physical activity; symptoms at rest

6-Minute Walk Test

Hemodynamic Parameters (mPAP, PVR, CO)

Survival

• Na+ and fluid restriction
• Maintain normal Hemoglobin/Hematocrit
• Cardiopulmonary rehabilitation
• Immunization
• Avoid air travel and high altitude
• Avoid pregnancy
• Support group and counseling

• Oxygen supplementation
• Diuretics (loop, metolazone, K-sparing diuretics)
• Warfarin (INR 1.5-2.5)
• Digoxin (usually in patients with comorbidities -- Afib, right sided heart failure)

• Calcium Channel Blockers
• Prostacyclin analogs
• Endothelin Receptor Antagonists
• Phosphodiesterase-5 Inhibitors
• Combination therapy

• Must show vasoreactivity in response to vasodilator testing
• Response is defined as decreased mPAP by > 10 mmHg to a value of < 40 mmHg without decrease in CO

• If no improvements to Class I or Class II after 3 months, consider additional or alternative PAH therapy

Nifedipine

Amlodipine

Diltiazem

Diltiazem

Because of Verapamil's negative inotropy effects, NOT recommended for PAH

• Epoprostenol
• Treprostinil
• Iloprost

• Must be given as continuous IV
• Improves 6-MWT, hemodynamics, QOL, and survival
• Approved for Classes III and IV
• First line for Class IV

• May be given SC, IV, or Inhaled
• Improves 6-MWT and hemodynamics
• Approved for Classes II, III, and IV
• First line for Class IV

• Inhaled frequently
• Improves 6-MWT and WHO-FC
• Approved for Classes III or IV

Adv

Most data

Effective in unstable and severe PAH

Disadv

Complicated drug preparation and delivery

Risk for line infections and sepsis

Adv

Longer half-life

Easier administration

Disadv

Infusion site pain limits use of effective dose

Adv

Inhaled route

Disadv

Frequent inhalations

• Bosentan
• Ambrisentan

• Dual receptor antagonist (ET_A >> ET_B)
• Improves 6-MWT, WHO-FC, hemodynamics, and time to progression
• Approved for Classes II-IV
• First line for II and III
• Monthly LFT and monthly pregnancy test required

• Selective ET_A receptor antagonist
• Improves 6-MWT, WHO-FC, hemodynamics, and time to progression
• Approved for Classes II or III
• First line for II and III
• Monthly LFT and monthly pregnancy test required

Sildenafil

Tadalafil

• First line as monotherapy for Classes II and III
• Add-on therapy for Class IV

Indicated only in patients who failed pharmacologic therapy

• Balloon Atrial Septostomy
• Pulmonary Thromboendarterectomy
• Lung or heart/lung transplant should be evaluated at the time of IV prostacyclin analog