Manual of Cardiovascular Diagnosis and Therapy

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CHAPTER 23. Cor pulmonale

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–Introduction. Cor pulmonale (CP) is defined as som...

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  1. Introduction. Cor pulmonale (CP) is defined as some combination of hyper-trophy and dilatation of the right ventricle secondary to pulmonary hypertension that results from a process intrinsic to the lung. Because of the latter provision, mitral stenosis or congenital cardiac defects producing right ventricular hypertrophy and dilatation are not classified as CP. CP may be acute, secondary to pulmonary embolism (see Chapter 22), or chronic (present chapter). A variety of conditions can produce CP (Table 23-1).

  2. Diagnosis

    1. History. The historical information obtained from a patient with CP varies with the underlying etiology (Table 23-1). Thus, patients with chronic obstructive pulmonary disease (COPD) and CP complain of dyspnea and cough with sputum production, whereas patients with primary pulmonary hypertension are likely to relate a history of dyspnea and exertional syncope. Dyspnea secondary to cardiac disease such as mitral stenosis should be excluded. In general, orthopnea and paroxysmal nocturnal dyspnea are secondary to pulmonary venous hypertension, itself a result of cardiac disease. Occasionally, paroxysms of bronchospasm secondary to bronchial asthma result in orthopnea and paroxysmal nocturnal dyspnea. When right ventricular failure occurs in patients with CP, fatigue, abdominal or ankle swelling, and anorexia are common complaints.

    2. Physical examination. Physical findings vary according to the underlying conditions that produced CP. Tachypnea, cyanosis, elevated jugular venous pressure, a right ventricular parasternal impulse, hepatomegaly, and peripheral edema often are noted, particularly in patients with right ventricular failure. Physical findings in CP are as follows (not all findings are present in all patients with CP):




      Elevated jugular venous pressure, often with a prominent A wave

      Abnormalities of the chest or lungs, depending on underlying condition causing CP

      Soft or inaudible heart sounds

      Right ventricular impulse palpated along left sternal border or in epigastrium

      Right ventricular third (S3) or fourth (S4) heart sounds (or both)—diastolic sound louder during inspiration

      Murmur of tricuspid insufficiency



      Peripheral edema

    3. ECG. The ECG usually demonstrates right ventricular hypertrophy and right atrial enlargement, although normal tracings are not uncommon in patients with CP. Atrial and ventricular arrhythmias are often found. ECG findings in CP are summarized in Table 23-2.

    4. Chest x-ray examination, computed tomography (CT). Pulmonary parenchymal, pleural, or thoracic cage abnormalities may be seen in chest roentgenograms and CTs of patients with CP, in accordance with the etiology of pulmonary hypertension. In addition, pulmonary hypertension and CP result in enlargement of the main pulmonary artery and right ventricle. Pulmonary arterial branches often taper rapidly toward the periphery of the lung, giving a "pruned tree" appearance to the pulmonary vasculature. Roentgenographic findings in patients with CP are summarized in Table 23-2. Pleural effusions and interstitial pulmonary edema are not seen unless pneumonia or left ventricular failure is also present.

    5. Laboratory tests. Patients with CP frequently have markedly abnormal pulmonary function tests and arterial blood gases. Depending on the underlying etiology, marked obstructive or restrictive (or mixed) pulmonary pathophysiology may be demonstrated by pulmonary function tests. Functional lung volume frequently is reduced. Arterial blood gas analysis may demonstrate notable hypoxia or even hypercapnia. Some individuals with CP have relatively normal arterial blood gases at rest but develop marked hypoxia and even hypercapnia with exercise, thus documenting the pulmonary etiology of their dyspnea. Patients with significant arterial hypoxia (arterial blood oxygen saturation greater than 90%) often develop secondary polycythemia.

    6. Echocardiography. Satisfactory transthoracic echocardiographic studies may be difficult to obtain in patients with CP, particularly if pulmonary hypertension is caused by COPD. Transesophageal echocardiographic studies are often required to delineate cardiac structures. When obtained, echocardiographic studies reveal an increased right ventricular cavity dimension and normal left-sided heart structures. The pulmonary valve echo may demonstrate loss of the normal A wave, a result of pulmonary hypertension. Doppler study often reveals tricuspid and pulmonic regurgitation and the degree of pulmonary hypertension can be quantitated.

    7. Radionuclide studies. Abnormal right ventricular ejection fraction can be documented in patients with CP by radionuclide ventriculography. Thallium myocardial scintigraphy can delineate increased right ventricular wall thickness.

    8. Catheterization and angiography. Right-sided pressures are usually markedly elevated in patients with CP. Pulmonary arterial systolic and mean pressures are invariably elevated, as is right ventricular systolic pressure. Pulmonary arterial diastolic pressure often is elevated, but pulmonary capillary wedge, left atrial, and left ventricular end-diastolic pressures are usually normal unless concomitant left ventricular disease is present. A number of investigators have noted abnormal left ventricular diastolic function in patients with pure CP, but the abnormalities are usually subtle and probably not of major clinical significance. Right ventricular end-diastolic and right atrial mean pressures are often normal at rest in patients with CP. Exercise or the onset of right ventricular failure results in elevated right ventricular filling pressures. Cardiac output is usually normal at rest but fails to rise appropriately with exercise.

      Left ventricular ejection fraction is ordinarily normal in patients with pure CP, but right ventricular ejection fraction often is reduced. Associated coronary artery disease is not uncommon in these individuals, particularly if they have COPD secondary to many years of heavy cigarette smoking.

    9. Protocol for the diagnosis of CP

      1. Testing sequence for making the diagnosis. The diagnosis of CP can be made according to the following diagnostic protocol. The dashed arrow indicates an optional step.

        History and physical examination

        Chest x-ray film/CT and ECG

        Pulmonary function tests and arterial blood gases


        Right and left ventricular radionuclide ventriculography or cardiac catheterization (or both)

      2. Criteria for making the diagnosis. The diagnosis of CP is made in patients with severe pulmonary or thoracic cage disease (Table 23-1)—documented by chest x-ray study, CT, pulmonary function tests, and arterial blood gases—who also demonstrate right ventricular hypertrophy or dilatation by any of the following: physical examination, chest x-ray film, ECG, and echocardiogram.

        Left-sided heart diseases (mitral stenosis, cardiomyopathy) must be ruled out by physical findings, chest x-ray examination, echocardiography, radionuclide ventriculography, and, if necessary, cardiac catheterization.

      3. Differential diagnosis

        1. Pulmonary venous hypertension. Dyspnea and right ventricular failure are frequently the result of pulmonary venous hypertension. The causes of pulmonary venous hypertension are many, commonly including mitral stenosis and various entities that lead to left ventricular failure. Dyspnea secondary to pulmonary venous hypertension (often referred to as cardiac dyspnea) usually involves orthopnea and paroxysmal nocturnal dyspnea, two symptoms usually absent in patients with pulmonary dyspnea. Mitral stenosis and the various entities that cause left ventricular failure (e.g., cardiomyopathy) can be distinguished from the numerous cases of CP by physical examination, ECG, echocardiography, and, on occasion, catheterization with measurement of pulmonary wedge pressure (normal in patients with CP).

        2. Constrictive pericarditis. Signs and symptoms resembling those of right ventricular failure are noted in patients with constrictive pericarditis. Individuals with the latter entity, however, have normal or mildly abnormal pulmonary function tests and arterial blood gases. Right ventricular enlargement or hypertrophy is almost invariably absent by physical examination, chest roentgenography, ECG, and echocardiography. Cardiac catheterization reveals the hemodynamic pattern of restriction to ventricular filling in patients with constrictive pericarditis.

  3. Therapy

    1. Medical treatment

      1. Treatment of underlying disorders. General and specific measures aimed at the underlying disorder that resulted in CP include cessation of cigarette smoking or exposure to other irritants in patients with chronic parenchymal pulmonary disease; specific antibiotic therapy and pulmonary toilet for infectious processes; and various combinations of bronchodilators, expectorants, corticosteroids, and oxygen when indicated. Individuals with pickwickian syndrome may benefit from progesterone and weight loss; those with myasthenia gravis usually are treated with anticholinesterase drugs and corticosteroids. Attention should not be focused on the therapy of right ventricular failure with exclusion of therapeutic regimens aimed at amelioration of the underlying condition that produced CP.

      2. Arrhythmias. Atrial and ventricular arrhythmias are common in patients with CP. Therapy aimed at the entity that resulted in CP often produces a concomitant improvement in right ventricular failure with a decrease in arrhythmias. Bronchodilators often have both beta1- and beta2-agonist activity, and use of these agents may actually precipitate or worsen arrhythmias. Supraventricular arrhythmias such as atrial tachycardia, atrial fibrillation, or atrial flutter generally are best treated with diltiazem or verapamil, digitalis, and possibly other antiarrhythmic agents such as amiodarone and, if required, electrical reversion. Verapamil, diltiazem, and other calcium channel blockers with electrophysiologic properties are very often useful in the control of supraventricular arrhythmias. Beta-blockers are contraindicated in patients with CP secondary to reactive airways disease. However, if the patient does not have reactive airways disease, small doses of beta-blockers may be tried during careful clinical observation. If the patient is having paroxysms of spontaneously reverting supraventricular arrhythmia, cardioversion usually is not helpful because it merely reestablishes sinus rhythm transiently. Therapy in this situation should involve diltiazem, verapamil, digitalis, or other antiarrhythmic medication.

        Patients with arterial hypoxia should be digitalized with care because some authorities believe that hypoxic myocardium has an increased susceptibility to digitalis intoxication. Beta-blocking agents should be used with considerable caution in patients with underlying pulmonary disease. Multifocal atrial tachycardia should not be managed with digitalis or antiarrhythmic drugs. Instead, attention is focused on improving the underlying pulmonary condition.

      3. Anticoagulants. Patients with recurrent pulmonary embolism should be treated with intravenous heparin for 7 to 10 days, followed by oral warfarin therapy for 2 to 6 months or longer. Patients with severe right ventricular failure are particularly predisposed to venous thrombosis and pulmonary embolism. Prophylactic long-term anticoagulation—often lifelong—with warfarin is often beneficial in such individuals, particularly if they are obese, are relatively inactive, and have signs and/or symptoms of heart failure.

      4. Vasodilators. Patients with CP frequently have marked pulmonary hypertension that eventually leads to right ventricular failure. Some clinical investigators have used vasodilators in these patients in an effort to dilate the pulmonary vascular bed and thereby decrease pulmonary arterial pressure and diminish right ventricular work. Such therapy has met with some success in selected patients. Nifedipine, a calcium channel blocker with potent vasodilatory properties, has been the most efficacious agent with regard to lowering pulmonary arterial pressure and vascular resistance. The dosage is usually 10 to 40 mg three or four times a day. Higher doses of calcium channel blockers have been reported to be of benefit in patients with severe primary pulmonary hypertension. The major side effects include headache, ankle swelling, gastrointestinal upset, and arterial hypoxia secondary to vasodilation of pulmonary capillaries that supply poorly ventilated lung regions. Diltiazem may be used in place of nifedipine. Selected patients with primary pulmonary hypertension and scleroderma heart disease can be markedly ameliorated with continuous intravenous infusions of prostacyclin. Pulmonary hypertension and CP regress when this therapy is successful.

    2. Surgery. An occasional patient with bronchiectasis or large emphysematous bullae benefits from a partial pulmonary resection. Pressure breathing devices, tracheostomy, or pharyngeal reconstruction can be of use in the management of some patients with sleep apnea. Patients with recurrent pulmonary embolism and CP may be candidates for inferior vena caval plication or interruption. Patients with chronic pulmonary embolism may benefit from pulmonary thromboendarterectomy of the chronic pulmonary arterial organized thrombus.

Selected Readings

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Alpert JS. Pulmonary hypertension. In: Goldman L, Bennett JC, eds. Cecil textbook of medicine. Philadelphia: Saunders, 2000:273–279.

Concise overview of pulmonary hypertension and its clinical concomitants.

Archer S, Rich S. Primary pulmonary hypertension: a vascular biology and translational research "work in progress." Circulation 2000;102:2781–2791.

A review of the vascular biology of primary pulmonary hypertension.

Badesch DB, Tapson VF, McGoon MD, et al. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease: a randomized, controlled trial. Ann Intern Med 2000;132:425–434.

Continuous epoprostenol therapy improves hemodynamics and exercise capacity in scleroderma patients with pulmonary hypertension.

Braman SS, Eby E, Kuhn C, et al. Primary pulmonary hypertension in the elderly. Arch Intern Med 1991;15:2433–2438.

Primary pulmonary hypertension occurs surprisingly often in elderly patients.

Cohen M, Edwards WD, Fuster V. Regression in thromboembolic type of primary pulmonary hypertension during 2 1/2 years of antithrombotic therapy. J Am Coll Cardiol 1986;7:172–175.

Pulmonary hypertension can be the result of recurrent episodes of pulmonary embolism; chronic anticoagulation results in regression of pulmonary hypertension in these patients.

D'Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension: results from a national prospective registry. Ann Intern Med 1991; 115:343–349.

Mortality in primary pulmonary hypertension is most closely associated with the degree of right ventricular dysfunction.

Hoeper MM, Schwarze M, Ehlerding S, et al. Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med 2000;342:1866–1870.

Long-term treatment with aerosolized iloprost improves exercise capacity and hemodynamics in patients with primary pulmonary hypertension.

Lilienfeld DE, Rubin LJ. Mortality from primary pulmonary hypertension in the United States, 1979–1996. Chest 2000;117:796–800.

Mortality from primary pulmonary hypertension seems to be increasing in the United States.

Morley TF, Zappasodi SJ, Belli A, et al. Pulmonary vasodilator therapy for chronic obstructive pulmonary disease and cor pulmonale: treatment with nifedipine, nitroglycerin, and oxygen. Chest 1987;92:71–76.

Therapy with vasodilators does not improve survival in patients with CP who are already receiving oxygen therapy.

Murphy ML, Adamson J, Hutcheson F. Left ventricular hypertrophy in patients with chronic bronchitis and emphysema. Ann Intern Med 1974;81:307–313.

Left ventricular hypertrophy in patients with COPD is usually the result of associated diseases that affect the left ventricle.

Rich S, Abenhaim L, eds. Primary pulmonary hypertension (monograph). Chest 1994; 105:1S.

A collection of papers covering up-to-date concepts on the pathophysiology, diagnosis, and therapy of primary pulmonary hypertension.

Rich S, Brundage BH. High-dose calcium channel blocking therapy for primary pulmonary hypertension: evidence for long-term reduction to pulmonary arterial pressure and regression of right ventricular hypertrophy. Circulation 1987;76:135–141.

High-dose calcium channel blocker therapy is effective in reducing pulmonary hypertension and right ventricular hypertrophy in patients with primary pulmonary hypertension.

Rubin LJ. Primary pulmonary hypertension. Chest 1993;104:236–250.

Consensus statement concerning definitions, pathophysiology, diagnosis, and therapy of primary pulmonary hypertension.

Saito S, Miyamoto K, Nishimura M, et al. Effects of inhaled bronchodilators on pulmonary hemodynamics at rest and during exercise in patients with COPD. Chest 1999;115:376–382.

Bronchodilators reduce right ventricular afterload in patients with COPD.

Wax D, Garofano R, Barst RJ. Effects of long-term infusion of prostacyclin on exercise performance in patients with primary pulmonary hypertension. Chest 1999;116: 914–920.

Exercise capacity is markedly improved by long-term infusion of prostacyclin in patients with primary pulmonary hypertension.