MANAGEMENT AND THERAPY OF SICKLE CELL DISEASE

NIH Publication No. 95-2117, Revised December 1995 (Third Edition) National Institutes of Health, National Heart, Lung, and Blood Institute

Chapter 20--Heart

The anemia of SS disease is usually well tolerated by the cardiovascular system for long periods. However, like other moderately severe anemias, cardiac function is ultimately affected. Physicians caring for patients with SS disease should be aware of cardiovascular involvement in these patients because the physician may be confronted with a variety of symptoms and physical findings similar to ventricular abnormalities, valvular dysfunction, and myocardial ischemia, which pose diagnostic and therapeutic difficulties.

CARDIAC FUNCTION

The reduced oxygen-carrying capacity due to anemia increases demand on the heart with an increased cardiac output. This chronic volume overload initiates compensatory responses, primarily cardiac enlargement. Although both dilation and hypertrophy frequently occur, systolic and diastolic performance of the left ventricle in the resting state is usually preserved. However, with radionuclide imaging studies and echocardiographic-derived indices, abnormalities in contraction and relaxation may be identified. In patients with these abnormalities, reduced peripheral vascular resistance maintains normal left ventricular systolic performance (as measured by ejection fraction). In the absence of coexistent cardiovascular disease, overt left ventricular failure is unusual in patients with sickle cell disease. However, symptoms such as dyspnea, palpitations, and easy fatigability frequently seen in these patients may lead to clinical misdiagnosis of heart failure. Without documented evidence of failure, treatment of symptoms with digitalis and diuretics is not indicated, and transfusion should be considered if the hemoglobin concentration is quite low. Right ventricular enlargement is less common and usually occurs in patients with pulmonary hypertension, which is a consequence of recurrent pulmonary artery thrombosis.

CHILDREN

Insights into the adaptation of children and adolescents to chronic anemia have been gleaned primarily from echocardiographic studies. Children with SS disease and hemoglobin levels in the range of 6 to 8 g/dl increase cardiac output at rest by 50 percent to meet the need for oxygen delivery to the tissues. This increase is achieved primarily through larger stroke volume, which results in the clinical findings of hyperdynamic circulation, heart murmur, and cardiomegaly. Cardiomegaly is a healthy adaptation to anemia and should not by itself be considered pathologic. Few children develop congestive heart failure in the absence of a sudden and profound decrease in hemoglobin concentration. Correction of severe anemia may require exchange blood transfusion (see Chapter 10, Transfusion). Most children and adolescents with sickle cell anemia successfully adapt to the increased cardiac demands posed by chronic anemia and usually have a reduced exercise capacity of 50 to 75 percent of that of unaffected children. Unlike adults, they are less likely to admit to exercise intolerance.

Because there is no evidence that exercise is harmful, and the beneficial effects of exercise are well known, children with sickle cell disease are encouraged to participate in physical activities and to set their own limits. If exercise-related symptoms occur, they should be evaluated with exercise electrocardiography. Fifteen percent of adolescents performing exercise stress tests develop S-T depression on electrocardiogram due to subendocardial ischemia. It is important to remember that children with SS disease are subject to the same medical conditions as other children, and findings that might suggest congenital, rheumatic, or other underlying heart disease should be investigated. In such cases, heart function is most reliably assessed by echocardiography and a cardiology consultation.

ADULTS

Exercise Performance Exercise capacity is reduced in most patients with SS disease. Most are able to achieve less than 50 percent of maximum predicted workloads. The cause for this decreased physical performance is likely multifactorial, and the role of cardiac dysfunction in this reduced work capacity is unclear. A significant number of these patients undergoing symptom-limited exercise testing develop S-T-segment depression on EKG, which appears to relate to older age, low level of hemoglobin, and the product of heart rate and systolic blood pressure. As described in children, these changes are due to subendocardial ischemia but are not associated with pain. Atherosclerotic coronary obstruction is unlikely to be the cause.

For patients seeking advice on exercise, participation in noncompetitive recreational activities should not be discouraged. However, exercise should not be performed to the point of exhaustion. The same general principle applies to work; that is, employment requiring a modest but not an exhausting degree of exertion is acceptable. Specific recommendations for conditioning exercise or training cannot be made at this time because of lack of available data. Exercise under adverse conditions, for example, cold weather, high altitude, or cold water exposure, should be avoided. Valvular Systolic murmurs are common in patients with SS disease, are usually best heard in the second and third intercostal spaces, and are a consequence of the increased cardiac output. However, basal diastolic murmurs are rare and should be considered pathologic when present. Structural valvular deformities do not appear to be increased in this disease. The prevalence of mitral valve prolapse has been reported to be high in patients with SS disease; however, this finding was not confirmed by the Special Cardiac Study of the Cooperative Study of the Clinical Course of Sickle Cell Disease.

Diagnostic Testing

Doppler echocardiography is recommended to assess a ardiac murmur suspected to be pathologic in origin.

* Resting and stress cardiac imaging studies (radionuclide or echocardiographic) are useful in determining cardiac chamber dimensions and global stolic function of both right and left ventricles.

* The utility of exercise testing in patients with exercise-induced chest pain is limited because exercise-induced EKG changes may not represent coronary obstructive disease. In individuals suspected of having coronary artery disease, this procedure should be supplemented with thallium myocardial perfusion scanning or dobutamine stress - echocardiography.

* Cardiac catheterization using contrast media has been performed safely in small numbers of patients with SS disease after partial exchange transfusion. Experience with this invasive procedure in sickle ell disease is limited and should be reserved for those patients in whom there is a high index of suspicion for the diagnosis of significant epicardial coronary artery disease and whose cardiac status cannot be satisfactorily evaluated by noninvasive testing. Dehydration resulting from the diuretic effect of the hypertonic contrast media must be avoided. Use of nonionic contrast material may prevent this complication.

Myocardial Infarction

Clinical and autopsy studies in adult patients demonstrate the infrequent occurrence of myocardial infarction in individuals with SS disease. Coronary anatomy in these patients is remarkable for the absence of significant atherosclerosis. However, a postmortem study of 70 patients with SS disease revealed that 17 percent had myocardial infarction or fibrosis despite normal coronary arteries. Recently, a group of patients with acute chest pain during sickle cell pain crisis was described with clinical evidence of myocardial ischemia or infarction. The role of red cell sickling in the pathogenesis of this phenomenon is unclear. Coronary spasm, as a secondary event of sickling, has been suggested as a mechanism.

Although coronary insufficiency is rare in patients with sickle cell disease, an electrocardiogram and cardiac enzymes should be obtained on all adult patients hospitalized with vaso-occlusive episodes and chest pain suggestive of myocardial ischemia or infarction. Sickle cell anemia is normally associated with dilated coronary arteries free of atherosclerotic plaque; however, newer diagnostic tests suggest that this does not preclude the development of myocardial ischemia or infarction.

BIBLIOGRAPHY

Alpert BS, Gilman PA, Strong WB, et al. Hemodynamic and ECG responses to exercise in children with sickle cell anemia. Am J Dis Child 1981;135:362-6.

Balfour IC, Covitz W, Arensman FW, et al. Left ventricular filling in sickle cell anemia. Am J Cardiol 1988;61:395-9.

Balfour IC, Covitz W, Davis H, et al. Cardiac size and function in children with sickle cell anemia. Am Heart J 1984;108:345-50.

Covitz W. Cardiac disease. In: Embury S, Hebbel RP, Mohandas N, Steinberg MH (eds). Sickle cell disease: basic principles and clinical practice. New York: Raven Press, 1994:725-34.

Covitz W, Eubig C, Balfour IC, et al. Exercise-induced cardiac dysfunction in sickle cell anemia. Am J Cardiol 1983;51:570-5.

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Gerry JL, Baird MG, Fortuin NJ. Evaluation of left ventricular function in patients with sickle cell anemia. Am J Med 1976;60:968-72.

Gerry JL, Buckley BH, Hutchins GM. Clinicopathologic analysis of cardiac dysfunction in 52 patients with sickle cell anemia. Am J Cardiol 1978;42:211-6.

Lewis JT, Maron BJ, Castro O, Moosa Y. Left ventricular diastolic filling abnormalities identified by Doppler echocardiography in asymptomatic patients with sickle cell anemia. J Am Coll Cardiol 1991;17:1473-8.

Miller GJ, Serjeant GR, Sivapragasam S, Petch MC. Cardiopulmonary responses and gas exchange during exercise in adults with homozygous sickle cell disease (sickle cell anemia). Clin Sci 1973;44:113-28.

Norris S, Johnson CS, Haywood TJ. Sickle cell anemia: does myocardial ischemia occur during crisis? J Natl Med Assoc 1991;83:209-13.

O'Neill B Jr, Saunders DE, McFarland DE, O'Neal H. Myocardial infarction in sickle cell anemia. Am J Hematol 1984;16:139-47.

Simmons BE, Santhanson V, Castaner A, et al. Sickle cell heart disease. Two dimensional echo and Doppler ultrasonographic findings in the hearts of adult patients with sickle cell anemia. Arch Intern Med 1988;148:1526-8.

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