A rare, frequently fatal disease, most commonly seen in women, that is best managed in centers with expertise in pulmonary hypertension.
Presenting symptoms and signs are nonspecific and include dyspnea on exertion, fatigue, and a loud pulmonary component of the second heart sound.
Diagnosis of exclusion. Transthoracic Doppler echocardiography and right heart catheterization can diagnose pulmonary hypertension. Laboratory tests and imaging studies can rule out known causes of pulmonary hypertension.
General supportive therapy includes oral anticoagulants, diuretics, supplemental oxygen, and digoxin.
Targeted treatment options include parenteral, inhaled, and oral prostanoids, oral endothelin receptor antagonists, oral phosphodiesterase type-5 inhibitors, the soluble guanylate cyclase stimulator riociguat, and the selective prostacyclin IP receptor agonist selexipag.
Prognosis is not good, as most patients eventually develop right ventricular failure.
Idiopathic pulmonary arterial hypertension (IPAH) is a disease of the small pulmonary arteries characterized by vascular proliferation and remodeling. It results in a progressive increase in pulmonary vascular resistance (PVR) and, ultimately, right ventricular failure and death. It is defined by a mean pulmonary arterial pressure ≥25 mmHg at rest with pulmonary capillary wedge pressure ≤15 mmHg and PVR >3 Woods units, without a known cause.
History and exam
Key diagnostic factors
- age 20-50 years
- female sex
- accentuated pulmonic component (P2) to the second heart sound
- tricuspid regurgitation murmur
- family history
Other diagnostic factors
- peripheral edema
- stimulant use
- chest pain
- near syncope
- early diastolic, high-pitched murmur in the pulmonary area
- jugular vein distension
- family history
- female sex
- bone morphogenetic protein receptor type 2 (BMPR2) mutations
- appetite suppressants
- drugs and toxins
1st investigations to order
- chest radiography
- transthoracic Doppler echocardiography
- right heart catheterization
- nocturnal oximetry
- ventilation-perfusion (V/Q) scintigraphy
- 6-minute walk test
- B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP)
- thyroid function tests
- HIV serology
Investigations to consider
- high-resolution chest CT scan ± CT pulmonary angiography
- vasodilator testing with inhaled nitric oxide, intravenous epoprostenol, or intravenous adenosine
positive response to acute vasoreactivity testing with no contraindication to calcium-channel blockers
negative response to acute vasoreactivity testing or calcium-channel blockers contraindicated
Gustavo A. Heresi, MD, MS
Director, Pulmonary Vascular and CTEPH Program
Department of Pulmonary and Critical Care Medicine
GAH has received speaking and advisory board fees from Bayer Healthcare, the manufacturer of riociguat.
Raed A. Dweik, MD
Pulmonary Vascular Program
Department of Pulmonary, Allergy, and Critical Care Medicine
RAD declares that he has no competing interests.
Michael J. Krowka, MD
Division of Pulmonary and Critical Care Medicine
Mayo Clinic College of Medicine
MJK declares that he has no competing interests.
Charlie Elliot, MB ChB, MRCP
Consultant Physician in Respiratory and General Internal Medicine
Sheffield Pulmonary Vascular Disease Unit
Royal Hallamshire Hospital
CE has received reimbursement for attending several conferences as well as lecture fees from Actelion Pharmaceuticals, GSK, and Bayer.
- Pulmonary arterial hypertension (PAH) associated with left heart diseases (pulmonary venous hypertension)
- PAH associated with lung respiratory diseases and/or hypoxia
- PAH due to chronic thrombotic and/or embolic disease
- Guidelines for the diagnosis and treatment of pulmonary hypertension
- Pharmacologic therapy for pulmonary arterial hypertension in adults: CHEST guideline and expert panel report
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