Excerpt from Pulmonary Hypertension, Secondary

Synonyms, Key Words, and Related Terms: 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, left ventricular dysfunction, LV dysfunction, mitral valvular disease, constrictive pericarditis, aortic stenosis, cardiomyopathy, poliomyelitis, myasthenia gravis, kyphoscoliosis, interstitial lung disease, HIV infection, toxins, portal hypertension, sickle cell disease, schistosomiasis, pulmonary capillary hemangiomatosis, deep venous thrombosis, pulmonary embolism, arthritis, arthralgias, heavy alcohol consumption, hepatitis, heavy snoring, daytime hypersomnolence, morning headaches, morbid obesity, hypertension, syncope, exertional angina, mitral stenosis, pulmonary artery distension, right ventricular ischemia, cor pulmonale, tricuspid regurgitation, hepatomegaly, pulsatile liver, ascites, left atrial hypertension, pulmonary venous obstruction, mediastinal fibrosis, pulmonary venoocclusive disease

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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, con .....