primary pulmonary hypertension (PPH)

Introduction

Primary pulmonary hypertension (PPH) is an uncommon disease of unknown etiology. It occurs most often in young to middle-aged women & usually results in death within several years of diagnosis.

Etiology

• genetic form(s)
• may occur in association with anorexiant use
• idiopathic

Epidemiology

• uncommon
• may occur from infancy throughout life
• primarily in young to middle-aged women
  • mean age at onset of 36 years

Pathology

• disease localized to small pulmonary arterioles resulting in high pulmonary vascular resistance
• plexiform lesions of proliferating endothelial cells in pulmonary arterioles
• lesions lead to elevated pulmonary arterial pressure, right ventricular failure, & death

Clinical manifestations

• clinical course is variable
• most patients present with advanced stages of disease
• gradual progressive dyspnea (90%)
• fatigue (25%)
• dizziness
• syncope (10%)
• right-sided angina (20%)
• hemoptysis (10%)
• cough (30%)
• hoarseness
• Raynaud's phenomenon (10%)
• loud P2
• right ventricular heave (80%)
• pulmonary ejection murmur (70%)
• S3 or S4 (50%)
• pulmonary regurgitation (20%)
• hepatomegaly (20%)
• peripheral edema
• ascites
• cyanosis

Diagnostic criteria

by exclusion

Laboratory

• antinuclear antibody (ANA) may be positive (40%)
• arterial blood gas (ABG) - exercise-induced hypoxia
• also see pulmonary hypertension

Diagnostic procedures

• pulmonary function testing
  • isolated decrease in DLCO with normal TLC, FEV & FEV1
• echocardiography
• electrocardiogram:
  • right axis deviation
  • tall R waves in V1, V2
  • ST segment depression
  • T wave inversion
  • right bundle branch block may occur
  • peaked T waves may be seen
• pulmonary artery catheterization with vasodilator test
  • IV vasodilator (adenosine, epoprostenol)
  • inhaled nitric oxide
  • vasoreactivity verified by
    • reduction in mean pulmonary artery pressure of at least 10 mm of Hg to a value <= 40 mm Hg
    • no decrease in cardiac output with vasodilation
• polysomnography as indicated
• open lung biopsy may be indicated
• also see pulmonary hypertension

Radiology

• chest radiograph
  • normal in 6% of patients
  • enlarged pulmonary arteries (90%)
  • pruning of peripheral vessels (50%)
  • clear lung fields
• V/Q scan to exclude multiple pulmonary emboli
• pulmonary angiography may be appropriate
• high-resolution lung CT to rule out interstitial lung disease
• also see pulmonary hypertension

Management

• supplemental oxygen in patients that are hypoxemic (SaO2 < 90%)
• chronic anticoagulation
  • chronic thromboembolic pulmonary hypertension (lifelong therapy)
  • this recommendation in the absence of thromboembolism not well understood
• calcium channel antagonists
  • invasive hemodynamic monitoring required to establish vasoreactivity before initiating therapy
  • effective in some patients with primary pulmonary hypertension & vasoreactivity on testing
  • may improve right ventricular function oxygen delivery survival
  • adverse effect of possibly worsening gas exchange
• if vasoreactivity testing negative
  • sildenafil, tadalafil
  • endothelin receptor antagonists (bosentan, ambrisentan)
• prostanoids reserve for patients with advanced disease
  • treprostinil
  • inhaled iloprost
  • intravenous prostacyclin (epoprostenol)
• diuretics
• beta-blockers pose significant risks, especially in patients without coexisting systemic hypertension, CAD & arrhythmia
• lung transplantation
• prognosis is poor:
  • generally results in death within several years of diagnosis

More general terms

• pulmonary hypertension; pulmonary arterial hypertension

More specific terms

• familial primary pulmonary hypertension