eMedicine Specialties > Pulmonology > Pulmonary Hypertension
Pulmonary Hypertension, Secondary
Updated: Jun 23, 2006
Introduction
Background
Secondary pulmonary artery hypertension (SPAH) is defined as a pulmonary artery systolic pressure higher than 30 mm Hg or a pulmonary artery mean pressure higher than 20 mm Hg secondary to either a pulmonary or a cardiac disorder. If no etiology can be identified, the pulmonary arterial hypertension (PAH) is termed primary pulmonary hypertension. An increased volume of pulmonary blood flow, escalating resistance in the pulmonary vascular bed, or an elevation in pulmonary venous pressure can induce the rise in pulmonary arterial pressure.
Cardiac disorders, pulmonary disorders, or both in combination are the most common causes of secondary pulmonary hypertension. Cardiac diseases produce pulmonary hypertension via volume or pressure overload, although subsequent intimal proliferation of pulmonary resistance vessels adds an obstructive element. Perivascular parenchymal changes along with pulmonary vasoconstriction are the mechanism of pulmonary hypertension in respiratory diseases.
Therapy for secondary pulmonary hypertension is targeted at the underlying cause and its effects on the cardiovascular system. Novel therapeutic agents such as prostacyclin and others undergoing clinical trials have led to the possibility of specific therapies for these once untreatable disorders.
Pathophysiology
Three predominant pathophysiologic mechanisms may be involved in the pathogenesis of SPAH, (1) hypoxic vasoconstriction, (2) decreased area of the pulmonary vascular bed, and (3) volume/pressure overload.
Hypoxic vasoconstriction
Chronic hypoxemia causes pulmonary vasoconstriction by a variety of actions on pulmonary artery endothelium and smooth muscle cells, including down-regulation of endothelial nitric oxide synthetase and reduced production of the voltage-gated potassium channel alpha subunit. Chronic hypoxemia leading to pulmonary hypertension can occur in patients with chronic obstructive pulmonary disease (COPD), high-altitude disorders, and hypoventilation disorders (eg, obstructive sleep apnea).
COPD is the most common cause of SPAH. These patients have worse 5-year survival rates, more severe ventilation perfusion mismatch, and nocturnal or exercise-induced hypoxemia. Other disorders, such as obstructive sleep apnea, neuromuscular disorders, and disorders of the chest wall, may lead to hypoxic pulmonary vasoconstriction and eventually SPAH.
Obliteration of pulmonary vasculature
A variety of causes may decrease the cross-sectional area of the pulmonary vascular bed, primarily due to disease of the lung parenchyma. The pulmonary arterial pressure rises only when the loss of the pulmonary vessels exceeds 60% of the total pulmonary vasculature. Patients with collagen vascular diseases have a high incidence of SPAH, particularly patients with systemic scleroderma or CREST (calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia) syndrome. A mild-to-moderate elevation in mean pulmonary artery pressure occurs secondary to acute pulmonary embolism. The peak systolic pressures usually do not rise above 50 mm Hg, and they generally normalize following appropriate therapy. Chronic pulmonary emboli can result in progressive PAH. HIV infection and several drugs and toxins are also known to cause PAH.
Volume and pressure overload
Disorders of the left heart may cause SPAH, resulting from volume and pressure overload. Pulmonary blood volume overload is caused by left-to-right intracardiac shunts, such as in patients with atrial or ventricular septal defects. Left atrial hypertension causes a passive rise in pulmonary arterial systolic pressure in order to maintain a driving force across the vasculature. Over time, persistent pulmonary hypertension accompanied by vasculopathy occurs. This may occur secondary to left ventricular dysfunction, mitral valvular disease, constrictive pericarditis, aortic stenosis, and cardiomyopathy.
Pulmonary venous obstruction is a rare cause of pulmonary hypertension. This may occur secondary to mediastinal fibrosis, anomalous pulmonary venous drainage, or pulmonary venoocclusive disease.
Frequency
United States
The frequency of secondary pulmonary hypertension is not known. Secondary pulmonary hypertension is observed as a complication of pulmonary or cardiac disorders, although not all patients with the underlying disorder develop this complication.
Mortality/Morbidity
Patients who develop SPAH have a poorer prognosis and higher mortality rates compared to those without SPAH, although no published reports document this in the literature.
Clinical
History
The clinical manifestations of SPAH are frequently masked by the underlying etiology. Obtaining a careful history may help exclude some of the numerous causes of secondary pulmonary hypertension. Important clues to a specific secondary cause include past history of heart murmur, deep venous thrombosis or pulmonary embolism, Raynaud phenomenon, arthritis or arthralgias, rash, heavy alcohol consumption, hepatitis, heavy snoring, daytime hypersomnolence, morning headaches, morbid obesity, and a family history of hypertension.
- Patients with SPAH often have nonspecific symptoms that reflect the underlying etiology.
- Other symptoms
- Dyspnea upon exertion
- Fatigue
- Lethargy
- Syncope with exertion
- Chest pain
- Less common symptoms
- Cough
- Hemoptysis
- Hoarseness (due to compression of the recurrent laryngeal nerve by the distended pulmonary artery)
- Typical exertional angina has been reported in as many as 8.5% of patients with SPAH secondary to mitral stenosis. This most likely occurs because of the pulmonary artery distension and/or right ventricular ischemia.
Physical
Physical examination findings may include the following:
- The intensity of the pulmonic component of the second heart sound (P2) may be increased, and a systolic ejection murmur may be heard over left sternal border. The P2 may demonstrate fixed or paradoxic splitting. A right ventricular heave may be palpated.
- A prominent a wave may be observed in the jugular venous pulse, and a right-sided fourth heart sound (S4) with a left parasternal heave may be heard.
- Right ventricular failure leads to systemic venous hypertension and cor pulmonale. Signs are the high-pitched systolic murmur of tricuspid regurgitation, hepatomegaly, a pulsatile liver, ascites, and peripheral edema. In this scenario, a right ventricular third heart sound is also heard.
- Signs of underlying cardiac, pulmonary, liver, or collagen vascular disease are often present.
Causes
Causes of secondary pulmonary hypertension can be divided based on primary pathophysiologic mechanisms, as follows:
- Hypoxic vasoconstriction
- Chronic obstructive pulmonary disease
- Sleep apnea, alveolar hypoventilation
- Neuromuscular diseases causing hypoventilation (eg, poliomyelitis, myasthenia gravis, kyphoscoliosis)
- Interstitial lung disease
- High-altitude residence
- Obliteration of pulmonary vasculature
- Collagen-vascular diseases
- Acute pulmonary embolism
- Chronic proximal pulmonary emboli
- HIV infection
- Toxins (rapeseed oil, crack cocaine)
- Portal hypertension
- Drugs (eg, fenfluramine, amphetamines, aminorex, chemotherapeutic drugs, tryptophan)
- Schistosomiasis
- Sickle cell disease
- Pulmonary capillary hemangiomatosis
- Volume and pressure overload
- Atrial and ventricular septal defects
- Left atrial hypertension secondary to mitral valve dysfunction or left ventricular dysfunction or systolic or diastolic dysfunction
- Pulmonary venous obstruction from lymphadenopathy, mediastinal fibrosis, or pulmonary venoocclusive disease (a rare idiopathic disorder that leads to SPAH)
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References
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Further Reading
Keywords
secondary pulmonary artery hypertension, SPAH, pulmonary artery hypertension, pulmonary arterial hypertension, PAH, cardiac disorders, pulmonary disorders, chronic obstructive pulmonary disease, COPD, high-altitude disorders, hypoventilation disorders, obstructive sleep apnea, OSA, collagen vascular diseases, systemic scleroderma, CREST syndrome, calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, telangiectasia, left heart disorders, atrial septal defects, ventricular septal defects
