Pulmonary Hypertension

Pulmonary Hypertension • Pulmonary hypertension is present when pulmonary artery pressure rises to a level inappropriate for a given cardiac output • Mean pulmonary artery pressure >25mmHg at rest or 30mmHg with exercise

Pathophysiology • • • •

The pulmonary circulation is unique because: High blood flow Low pressure (normally 25/8 mm Hg, mean 12) Low resistance (normally 200–250 dynes/sec/cm–5)

• It can accommodate large increases in blood flow during exercise with only modest increases in pressure because of its ability to recruit and distend lung blood vessels • Contraction of smooth muscle in the walls of pulmonary artery makes arteriolar resistance an important factor in numerous pathologic states

• Once present, pulmonary hypertension is selfperpetuating • It introduces secondary structural abnormalities in pulmonary vessels, including smooth muscle hypertrophy and intimal proliferation • These may eventually stimulate atheromatous changes and in situ thrombosis, leading to further narrowing of the arterial bed

Types of Pulmonary Hypertension Primary (idiopathic) pulmonary hypertension • Rare disorder of the pulmonary circulation occurring mostly in young and middle-aged women • Characterized by progressive dyspnea, a rapid downhill course, and an invariably fatal outcome • It has been observed in occasional patients with HIV infection.

Secondary pulmonary hypertension • Pulmonary arteriolar vasoconstriction due to chronic hypoxemia may complicate any chronic lung disease and compound the effects of loss of pulmonary blood vessels (as seen with disorders such as emphysema and pulmonary fibrosis) and obstruction of the pulmonary vascular bed (as seen with disorders such as chronic pulmonary thromboembolic disease)

• Sustained increases in pulmonary venous pressure from disorders such as left ventricular failure (systolic, diastolic, or both), mitral stenosis, and pulmonary veno-occlusive disease may cause "postcapillary" pulmonary hypertension • Increased pulmonary blood flow due to intracardiac shunts and increased blood viscosity due to polycythemia can also cause pulmonary hypertension • Pulmonary hypertension has also been associated with hepatic cirrhosis and portal hypertension.

Pulmonary veno-occlusive disease • Rare cause of postcapillary pulmonary hypertension occurring in children and young adults • The cause is unknown, but associations with various conditions such as viral infection, bone marrow transplantation, chemotherapy, and malignancy have been described • The disease is characterized by progressive fibrotic occlusion of pulmonary veins and venules, along with secondary hypertensive changes in the pulmonary arterioles and muscular pulmonary arteries. • There is no effective therapy, and most patients die within 2 years as a result of progressive pulmonary hypertension.

Mechanisms of pulmonary hypertension and examples of corresponding clinical conditions. Reduction in cross-sectional area of pulmonary arterial bed     • Vasoconstriction      • •

Hypoxemia from any cause (chronic lung disease, sleep-disordered breathing, etc)      Acidosis  

• Loss of vessels      • •

Lung resection      Emphysema     

• • •

Vasculitis      Interstitial lung disease      Collagen-vascular disease   

• Obstruction of vessels      • • • •

Pulmonary embolism (thromboemboli, tumor emboli, etc)      In situ thrombosis      Schistosomiasis      Sickle cell disease   

• Narrowing of vessels      •

Secondary structural changes due to pulmonary hypertension

• Increased pulmonary venous pressure     • • • • • •

Constrictive pericarditis    Left ventricular failure or reduced compliance    Mitral stenosis    Left atrial myxoma    Pulmonary veno-occlusive disease    Mediastinal diseases compressing pulmonary veins

• Increased pulmonary blood flow    • Congenital left-to-right intracardiac shunts

• Increased blood viscosity    • Polycythemia

• Miscellaneous   

• Pulmonary hypertension occurring in association with hepatic cirrhosis and portal hypertension    • HIV infection

Clinical Findings Symptoms • Early stages symptoms and signs are primarily those of the underlying disease • Pulmonary hypertension may cause or contribute to dyspnea, present initially on exertion and later at rest • Dull, retrosternal chest pain resembling angina pectoris may be present • Fatigue and syncope on exertion, presumably a result of reduced cardiac output related to elevated pulmonary artery pressures or bradycardia

Signs • Narrow splitting of the second heart sound • Accentuation of the pulmonary component of the second heart sound • Systolic ejection click • In advanced cases, tricuspid and pulmonary valve insufficiency and signs of right ventricular failure and cor pulmonale are found

Laboratory Findings • Polycythemia is found in many cases of pulmonary hypertension that are associated with chronic hypoxemia • Electrocardiographic changes • • • •

Right Right Right Right

axis deviation ventricular hypertrophy ventricular strain atrial enlargement

Imaging and Special Examinations • Radiographs and high-resolution CT scans of the chest can assist in the diagnosis of pulmonary hypertension and determination of the cause • Echocardiography is helpful in evaluating patients thought to have mitral stenosis, left atrial myxoma, and pulmonary valvular disease and may also reveal right ventricular enlargement • Doppler ultrasonography is a reliable noninvasive means of estimating pulmonary artery systolic pressure • Precise hemodynamic measurements can only be obtained with Right heart catheterization, which is helpful when postcapillary pulmonary hypertension, intracardiac shunting, or thromboembolic disease is considered as part of the differential diagnosis

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The X-ray shows gross enlargement of the cardiac silhouette

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The right border extends far to the right indicating gross right atrial enlargement

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Presence of an associated pericardial effusion cannot be ruled out

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Pulmonary vasculature is not so prominent indicating that the right atrial enlargement may be due to severe pulmonary hypertension and right ventricular failure.

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Organic tricuspid valve disease has to be considered as the cause for right atrial enlargement in this situation.

Treatment • Treatment of secondary pulmonary hypertension consists mainly of treating the underlying disorder • Early recognition of pulmonary hypertension is crucial to interrupt the self-perpetuating cycle responsible for rapid clinical progression • By the time most patients present with signs and symptoms of pulmonary hypertension, however, the condition is far advanced

• If hypoxemia or acidosis is detected: Supplemental oxygen administered for at least 15 hours per day has been demonstrated to slow the progression of pulmonary hypertension in patients with hypoxemic COPD • Permanent anticoagulation is indicated in primary pulmonary hypertension but should be given only to those patients with secondary pulmonary hypertension at high risk for thromboembolism

Vasodilator therapy • Therapy with pharmacologic agents (eg, calcium antagonists, hydralazine, isoproterenol, diazoxide, nitroglycerin) has shown disappointing results in secondary pulmonary hypertension • Patients most likely to benefit from long-term pulmonary vasodilator therapy are those who respond favorably to a vasodilator challenge at right heart catheterization • It is clear that long-term oral vasodilator therapy should be used only if hemodynamic benefit is documented

• Continuous long-term intravenous infusion (using a portable pump) of prostacyclin (PGI2; epoprostenol), a potent pulmonary vasodilator, has been shown to confer hemodynamic and symptomatic benefits in selected patients with primary or secondary pulmonary hypertension. This is the first therapy to demonstrate improved survival of patients with primary pulmonary hypertension. • Newer agents in research trials include subcutaneous (treprostinil), inhaled (iloprost), and oral (beraprost) prostacyclin analogues, endothelin receptor antagonists (bosentan), and phosphodiesterase inhibitors (sildenafil)

• Patients with marked polycythemia (hematocrit > 60%) should undergo repeated phlebotomy in an attempt to reduce blood viscosity • Cor pulmonale complicating pulmonary hypertension is treated by managing the underlying pulmonary disease and by using diuretics, salt restriction, and, in appropriate patients, supplemental oxygen • Pulmonary thromboendarterectomy may benefit selected patients with pulmonary hypertension secondary to chronic thrombotic obstructions of major pulmonary arteries • Single or double lung transplantation may be performed on patients with end-stage primary pulmonary hypertension

Prognosis • The prognosis in secondary pulmonary hypertension depends on the course of the underlying disease • The prognosis is favorable when pulmonary hypertension is detected early and the conditions leading to it are readily reversed • Patients with pulmonary hypertension due to fixed obliteration of the pulmonary vascular bed generally respond poorly to therapy