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Fibroelastosis in children
Fibroelastosis in Children By JAMES A. MANNINGAND JOHN D. KEITH
H E TERM ENDOCARDIAL FIBROELASTOSIS was first used by Weinberg and Himelfarb I to describe the syndrome of infantile eardiomegaly in which the pathologic lesicn consisted of varying degrees of fibroelastotic proliferation within the endocardium. It is now well recognized that there are at least two forms of this process. One is associated with numerous eongenital heart defects, notably of the left side of the heart, and appears to be secondary to them or has occurred simultaneously during their development. The other is apparently a primary phenomenon, associated with marked endocardial thickening but with no associated anatomic lesions of significance. The pathologic picture is sufficiently characteristic for pathologists to recognize it as a distinct entity, and it has been termed Primary Endocardial Fibroelastosis. 2 This communication will review present information on primary endoeardial fibroelastosis and will present the authors" view on clinical diagnosis and management based on experience with over 56 patients clinically diagnosed and medically managed over the last decade2 ,4 Pathology: The pathology of this process consists of a whitish thickening of the endocardium of the left ventricle and left atrium. There is diffuse involvement of the entire chambers not just isolated areas of thickening and not affecting only the inflow and outflow tracts. Frequently, the mitral and aortic valves are thickened and scarred. The involved chambers are dilated and the myocardinm is thickened. Rarely, the right side of the heart is involved; and rarely, the involved chambers are contracted and small with thickened musculature. Histologically, the endocardium is much thicker than usual; and strands of fibroelastie proliferation extend into the subendocardial layers and even into the myocardium which is grossly hypertrophied2 ,2,5 Etiology: The etiology of this process is as yet unknown. Indeed, whether it is truly a primary process, or whether it is a secondary, nonspecific response to a variety of undefined cardiac stresses, remains a subject for debate and investigation2 ,7 Fetal endocarditis, s obstruction to subendoeardial lymph drainage? blockage of Thebesian vessels, and premature closure of the foramen ovale 1~ have all been considered as possible causal modalities. The relationship of mumps infection or other myxovirus infection will be reviewed later in this text. Studies of pregnancy history, birth rank, birth weight, sex ratio, and maternal age have been unrewarding to presentY ,3 Multiple cases within families have been regularly reported; 2,3 and in our experience, almost one-third of
T
From the Strong Memorial Hospital, Rochester, New York, and the Hospital for Sick Children, Toronto, Ontario. 172 PROGRESS IN CARDIOVASCULARDISEASES, VOL. 7, No. 9. (SEPTEMBER), 1964
FIBROELASTOSIS IN CHILDREN
173
necropsy-proved cases have been in sibships. Thus, the role of familial predilection or even genetic determination must be considered in any etiologic evaluation. Clinical Picture: The age of onset of clinical symptomatology can vary considerably and has been described all through the pediatric age range 2,11 and indeed into adult life. 12,13 However, by far the greatest number present with clinical difficulties in the first year of life and, if not by then, almost uniformly by the end of the second year. ~,14,15 The symptomatology is basically that of congestive heart failure of the so-called "low-output" variety. The onset of symptoms may be abrupt and fulminating, may be over the course of several weeks, or may be insidious and over several months. 3,16 Taehypnea, dyspnea, lethargy, easy tiring, and poor appetite are the most common clinical manifestations. Cyanosis is noted only in patients seen at a time of extreme cardiac collapse. There is only occasionally a history of preceding respiratory infection or other nonspeeific illness. Thus~ in general, the story is one of a previously well-developed, nourished, and thriving infant developing the above described symptoms and findings. Physical Findings: In general, the physical findings are again the nonspecific ones of low-output left-sided heart failure. There is marked taehypnea and tachycardia. The diminished cardiac output is reflected in extreme pallor and occasionally eyanosis. Peripheral pulses are all weak, and the pulse pressure may be narrow. The preeordium is quiet and the apical impulse is poorly felt. The heart sounds may be muffled, of tie-toe or poor muscular quality, and a gallop rhythm is often heard. There are either no murmurs or there are variable murmurs arising fu the mitral and aortic valves, usually mitral insufficiency and aortic stenosis. A striking characteristic is the variability and evanescence of these murmurs from day to day and with minor changes in the clinical status. The ptdmbnary second sound is usually moderately accentuated, and the aortic second sound is generally normal. Signs of congestive heart failure are dramatic, and there is often marked generalized edema and hepatomegaly. Despite the left-sided heart involvement, pulmonary edema is uncommon. Fluoroscopic and Roentgen Findings: The heart is grossly enlarged, and routinely the cardio:thoracic ratio is between 60 and 75 per cent or greater. The most striking characteristic of the fluoroscopy is that there is minimal evidence of volume alteration between systole and diastole. A quiet heart is seen although the distinctive features of individual chambers are retained, and there should be little confusion between this heart and the silhouette of pericardial effusion. The left ventricle and left atrium are grossly dilated and inactive. The lungs are usually remarkably clear, although there may be evidence of pulmonary venous congestion. Compression ateleetasis of the lower lobe of the left lung is not uncommon. The Electrocardiogram: The electrocardiogram in this syndrome is strik-
174
MANNING AND KEITH
ing and serves as a major differential point from other causes of primary myocardial failure in infancy and childhood. It is characterized by a marked left ventrieular hypertrophy pattern of increased voltage and flattened or inverted T waves over the left precordial leads. This hypertrophy pattern is generally one of a tall R wave in lead V6 exceeding 20 mm. and a deep S wave in V1 of greater than 20 ram. The electrical axis in the frontal plane may remain essentially normal or may shift slightly to the left. The direction of the frontal loop is almost routinely clockwise. When one is confronted with the problem of primary myocardial disease, particularly when the onset is under the age of 2 years, the period of greatest frequency of primary endoeardial fibroelastosis, this pattern is strikingly characteristic), 17,18 Hemodynamics: Most patients have not been subjected to hemodynamic studies. When done, usually after initial clinical stabilization, they have shown elevation of pulmonary artery and pulmonary wedge pressures. The end-diastolic pressure of the left ventricle has been elevated. Cardiac output is low and stroke volume diminished2 s,19 Angiocardiography: Angioeardiographic studies have shown poor systolic emptying of the left ventricle with retention of dye in the left side of the heart and evidence of a small stroke volume2 s,19 Some authors have emphasized these findings as quite characteristic for the disease. 1s,1~ Our experience would agree with this, but we would not feel that in most eases it was a necessary adjunct to diagnosis. Endocardial Biopsy: We do not feel that at the present time this procedure justifies its risk. However, it has been used to confirm the pathologic histology, both at operation and by punch biopsy, in patients doing well on medical management?, 21 Skin Test: Recent observations have raised the possibility that the mumps skin test may be of diagnostic value in primary endocardial fibroelastosis, 22 particularly under the age of 2 years. In our experience at the present time, results may be variable. However, our present feeling is that a positive mumps skin test in the first 2 years of life is strong supportive evidence if the rest of the clinical picture is present. A negative mumps skin test result during this period appears to be evidence against the diagnosis. The meaning of this observation is not clear. There has been no history of clinical mumps in either the infants or in their parents or families. Whether this represents a skin reaction to one of the other viruses of the myxovirus group or whether this is a nonspeeifie antigen response, remains to be seen. Method of Management: It is our opinion based on our clinical experience over the past 10 years that with vigorous and sustained medical management, approximately 75 per cent of patients with the clinical diagnosis of primary endoeardial fibroelastosis will survive. Furthermore, nearly 80 per cent of these survivors will revert to a status with an essentially normal heart s~ze and a normal electrocardiogram and will be maintained symptom-free without digitalis therapy. 4
FIBIAOELASTOSISIN CHILDBEN
175
Vigorous and sustained medical m a n a g e m e n t to us means standard presentday methods of decongestive therapy. Using a route of digitalis administration appropriate to the severity of the clinical state, most have been digitalized with between 60 and 80 ~g. o[ Digoxin per Kg. M a ~ t e n a n c e dosage, divided into 2 daily doses, has been between 12 and 25 ~g. of Digoxin per Kg. W h e n necessary, these patients have been supported with oxygen, diuretics, and low salt diet; and they have been subjected to extremely careful longterm medical supervision. 4,a4,18 Experience with steroids and revascularization technics 2a has in general been unsatisfactory TM and at present neither appears to have a substantial place in therapy. A brief summary of our feelings and experience in regard to medical management is as follows. 1. In general, prognosis is better in patients with a subacute or chronic type of onset o~ symptomatology, although 50 per cent of patients presenting with an acute or fulminating onset can be saved. 2. The initial response to therapy is a good index to long-term prognosis. Most deaths occur within the first 2 months of medical management, and most good clinical results will show a significant decrease in heart size during this period. 3. Approximately 70 per cent of good results will have a cardio:thoracic ratio below 55 per cent by the end of 2 years of therapy. 4. Approximately tile same per cent of good results will show a normal electrocardiogram between 2 and 5 years after the onset of therapy.
Duration of Therapy: In general, these patients have required between 3 and 5 years of digitalis therapy. W e have not discontinued digitalis in patients whose cardio:thoracic ratio remained above 55 per cent. We have not discontinued digitalis in a symptomatic patient. Our general policy is to stop therapy gradually, u n d e r careful medical supervision, 2 years after the end of all symptoms, with stabilization of the cardio:thoracic ratio below 55 per cent, and the reversion of the electrocardiogram, including the left ventricular T waves, to a normal state. Differential Diagnosis: A brief review of the more common and difficult problems in differentiai diagnosis with a r6sum6 of major differential points is as follows. 1. Acute myocarclitis: Associated with present or preceding specific infection. Other than epidemic Coxsackie myocarditis of the new born period, age of onset is scattered throughout pediatric age range, rather than concentrated in infantile period. EKG rarely shows hypertrophy patterns and is more likely to show bizarre conduction defects, low voltage QtlS, and S-T segment abnormalities.3,17,is 2. Idiopathic or familial myocardial hypertrophy. Uncommonly display high voltage left ventricular hypertrophy pattern. Unlikely to present as dilated, hypodynamic left side of the heart. In general, do not present in infancy in congestive heart failure. Mode of difficulties and death more likely sudden arrhythmia. 3. Chronic anemic heart disease: May present with identical EKG, however, they have evidence of major anemia. Heart is hyperdynamic and high output in character, rather than hypodynamic and low output. Rapid response to repair of anemia in terms of cardiac reserve although cardiomegaly and electrocardiographic changes persist. Flow murmurs present.
176
MANNING AND KEITH
4. Anomalous origin o~ left coro,mry artery: Age of onset of symptoms usually between ages 2 and 4 months. EKG shows pattern of anterolateral myocardial infarction, rarely a high voltage hypertrophy pattern. When in doubt, coronary angiography can confirm or exclude diagnosis.14,15,18,z4 5. Glycogen storage disease of the heart: Usually show general muscle involvement. Muscle biopsy should be diagnostic. EKG rarely shows more than minimal hypertrophy pattern. No present evidence of survivors past infancy. 6. Secondary Endocardial Fibroelastasis or fibroelastosis associated with significant valvular or other left-sided heart obstructive lesions': Difficult to fully differentiate. Hemodynamic significance (murmurs, etc.) of anatomic lesions may be clue. Severe electrocardiographic changes with lesser evidence of hemodynamic significance may be clue to combined lesion.
The above 6 have been our basic troublemakers. Many other entities have been mentioned in differential diagnosis, but we exclude them by their specific diagnostic characteristics or, occasionally, by rarity. They include idiopathic calcification of coronary arteries, systemic hypertension, paroxysmal tachycardias, cardiac involvement in generalized neuromuscular disease, and acute pericarditis. It should be remembered that primary endocardial fibroelastosis is far more common as a cause of infantile congestive heart failure than any of the above-mentioned entities. The mumps skin test result appears to be negative in all of these including secondary endocardial fibroelastosis. General Comments: Any discussion of the clinical syndrome of primary endocardial fibroelastosis remains unsatisfactory in the void of etiologic knowledge and the absence of definition that this is a specific syndrome with a specific cause. Furthermore, any objective review of an analysis of medical management in this syndrome must take into account the reluctance of many workers to accept the validity of clinical diagnosis, r,l~ Despite this, we would reiterate the view that the diagnostic criteria, when taken as a group, are highly specific2,18 Edwards 25 and Lynfield19 divide patients into a type I, characterized by a dilated left side of the heart, and type II, characterized by a normal or contracted left side of the heart. In our experience, 'the clinical syndrome so regularly associated with fibroelastosis and recognizable by the criteria discussed here, is almost uniformly type I. We, as do others, TM find type II hearts associated with major congenital cardiac anomalies. Such a review as this raises more questions than it answers. In addition to those already reviewed, we might cite the following. The mechanism of response to therapy has not been defined. The fate of the pathologic endocardium in surviving patients is unknown. Long-term hemodynamic observations and the long-term natural history of these patients after medical stabilization need to be documented. Until these gaps have been filled, the consideration of fibroelastosis must remain descriptive and somewhat speculative. All we can really do at the
177
FIBROELASTOSIS IN CHILDBEN
present time is to point out that a body of experience exists which allows us to clinically define a major segment of the clinical spectrum. Furthermore, our experience in clinical management has led us to the definition of a reasonably good prognosis for survival and stability with vigorous and sustained medical management. REFERENCES 1. Weinberg, T., and Himelfarb, A. J.: Endocardial fibroelastosis. Bull. Johns Hopkins Hosp. 72:299, 1943. 2. Anderson, D. H., and Kelly, J.: Endocardial fibroelastosis: 1. Endocardial fibroelastosis associated with cong e n i t a l malformations of the heart. Pediatrics 18:513, 1956. 3. Sellers, F. J., Keith, J. D., and Manning, J. A.: Diagnosis of primary endocardial fibroelastosis. Circulation 29:49, 1964. 4. Manning, J. A., Sellers, F. J., Bynum, R. S., and Keith, J. D.: Medical management of clinical endocardial fibroelastosis. Circulation 29:60, 1964. 5. Still, W. J. S.: Endocardial fibroelastosis. Am. Heart J. 61:579, 1961. 6. Black-Schaffer, B.: Infantile endocardial fibroelastosis. Arch. Path. 63:281, 1957. 7. Lambert, E. C., and Vlad, P.: Primary endomyocardial disease. Pediat. Clin. North America 1958. 8. Gross, P.: Concept of fetal endocarditis: a general review with report of an illustrative case. Arch. Path. 31:163, 1941. 9. Miller, A. J., Pick, R., and Katz, L. N.: Ventricular endomyocardial pathology following chronic impairment of cardiac lymph flow in the dog. Brit. Heart J. 25:182, 1963. 10. Johnson, F. R.: Anoxia as a cause of endocardial fibroelastosis in infancy. Arch. Path. 54:237, 1952. 11. Blumberg, R. W., and Lyon, R. A.: Endocardial sclerosis. Am. J. Dis. Child. 84:291, 1952. 12. Auld, W. H. g., and Watson, H.: Fibroelastosis of the heart in adolescence. Brit. Heart J. 19:186, 1957. 13. Thomas, W. A., Randall, R. V., Bland, E. F., and Castleman, B.: Endocardial fibroelastosis: A factor in heart
14.
15.
16.
17.
18.
191
20.
21.
22.
23.
disease of obscure etiology: a study of 20 autopsied cases in children and adults. New Eng. J. Med. 251:327, 1954. Keith, J. D., Rowe, R. D., and Vlad, P.: Heart Disease in Infancy and Childhood. New York, Macmillan Co., 1958. Nadas, A. S.: Pediatric Cardiology. Philadelphia, W. B. Saunders Co., 1963, p. 272. Dennis, J. L., Hansen, A. E., and Corpening, T. N.: Endocardial fibroelastosis. Pediatrics 12:130, 1953. Vlad, P., Rowe, R. D., and Keith, J. D.: The electrocardiogram in primary endocardial fibroelastosis. Brit. Heart J. 17:189, 1955. Linde, L. M., and Adams, F. H.: Prognosis in endocardial fibroelastosis. J. Dis. Child. 105:329, 1963. Lynfield, ]., Gasul, B. M., Luan, L. L., and Dillon, R. F.: Right and left heart catheterization and angioeardiographie findings in idiopathic cardiac hypertrophy with endocardial flbroelastosis. Circulation 21: 386, 1960. Linde, L. M., Adams, F. H., and O'Loughlin, J. J.: Endocardial fibroelastosis: angiocardiographic studies. Circulation 17:40, 1958. D~court, L. V., Maeruz, R., Carcia, D. P., and Todoni, H.: Endocardial fibroelastosis: its study by punch-biopsy of the heart. Fourth World Congress of Cardiology, Mexico City, 1962. Noren, G. R., Adams, P., and Anderson, R. C.: Positive skin reactivity to mumps virus antigen in endocardial fibroelastosis. J. Pediat. 62:604, 1963. Paul, R. N., and Bobbins, S. C.: Surgical treatment for endocardial flbroelastosis or anomalous left coronary artery. Am. J. Cardiol. 1:694, 1958.
MANNING AND KEITH
178 24. Sabiston, D. C., Jr., Neill, C. A., and Taussig, H. B.: The direction of blood flow in anomalous left coronary artery arising from the pulmonary artery. Circulation 22:591, 1960.
James A.
Manning,
25. Edwards, J. E.: Congenital malformations of the heart and great vessels. In Gould, S. E.: Pathology of the Heart. Springfield, Ill., Charles C Thomas, 1953, p. 266,
M.D., Strong Memorial Rochester, N. Y.
Hospital,
]ohn D. Keith, M.D., The Hospital for Sick Children, Toronto, Ontario.
H E TERM ENDOCARDIAL FIBROELASTOSIS was first used by Weinberg and Himelfarb I to describe the syndrome of infantile eardiomegaly in which the pathologic lesicn consisted of varying degrees of fibroelastotic proliferation within the endocardium. It is now well recognized that there are at least two forms of this process. One is associated with numerous eongenital heart defects, notably of the left side of the heart, and appears to be secondary to them or has occurred simultaneously during their development. The other is apparently a primary phenomenon, associated with marked endocardial thickening but with no associated anatomic lesions of significance. The pathologic picture is sufficiently characteristic for pathologists to recognize it as a distinct entity, and it has been termed Primary Endocardial Fibroelastosis. 2 This communication will review present information on primary endoeardial fibroelastosis and will present the authors" view on clinical diagnosis and management based on experience with over 56 patients clinically diagnosed and medically managed over the last decade2 ,4 Pathology: The pathology of this process consists of a whitish thickening of the endocardium of the left ventricle and left atrium. There is diffuse involvement of the entire chambers not just isolated areas of thickening and not affecting only the inflow and outflow tracts. Frequently, the mitral and aortic valves are thickened and scarred. The involved chambers are dilated and the myocardinm is thickened. Rarely, the right side of the heart is involved; and rarely, the involved chambers are contracted and small with thickened musculature. Histologically, the endocardium is much thicker than usual; and strands of fibroelastie proliferation extend into the subendocardial layers and even into the myocardium which is grossly hypertrophied2 ,2,5 Etiology: The etiology of this process is as yet unknown. Indeed, whether it is truly a primary process, or whether it is a secondary, nonspecific response to a variety of undefined cardiac stresses, remains a subject for debate and investigation2 ,7 Fetal endocarditis, s obstruction to subendoeardial lymph drainage? blockage of Thebesian vessels, and premature closure of the foramen ovale 1~ have all been considered as possible causal modalities. The relationship of mumps infection or other myxovirus infection will be reviewed later in this text. Studies of pregnancy history, birth rank, birth weight, sex ratio, and maternal age have been unrewarding to presentY ,3 Multiple cases within families have been regularly reported; 2,3 and in our experience, almost one-third of
T
From the Strong Memorial Hospital, Rochester, New York, and the Hospital for Sick Children, Toronto, Ontario. 172 PROGRESS IN CARDIOVASCULARDISEASES, VOL. 7, No. 9. (SEPTEMBER), 1964
FIBROELASTOSIS IN CHILDREN
173
necropsy-proved cases have been in sibships. Thus, the role of familial predilection or even genetic determination must be considered in any etiologic evaluation. Clinical Picture: The age of onset of clinical symptomatology can vary considerably and has been described all through the pediatric age range 2,11 and indeed into adult life. 12,13 However, by far the greatest number present with clinical difficulties in the first year of life and, if not by then, almost uniformly by the end of the second year. ~,14,15 The symptomatology is basically that of congestive heart failure of the so-called "low-output" variety. The onset of symptoms may be abrupt and fulminating, may be over the course of several weeks, or may be insidious and over several months. 3,16 Taehypnea, dyspnea, lethargy, easy tiring, and poor appetite are the most common clinical manifestations. Cyanosis is noted only in patients seen at a time of extreme cardiac collapse. There is only occasionally a history of preceding respiratory infection or other nonspeeific illness. Thus~ in general, the story is one of a previously well-developed, nourished, and thriving infant developing the above described symptoms and findings. Physical Findings: In general, the physical findings are again the nonspecific ones of low-output left-sided heart failure. There is marked taehypnea and tachycardia. The diminished cardiac output is reflected in extreme pallor and occasionally eyanosis. Peripheral pulses are all weak, and the pulse pressure may be narrow. The preeordium is quiet and the apical impulse is poorly felt. The heart sounds may be muffled, of tie-toe or poor muscular quality, and a gallop rhythm is often heard. There are either no murmurs or there are variable murmurs arising fu the mitral and aortic valves, usually mitral insufficiency and aortic stenosis. A striking characteristic is the variability and evanescence of these murmurs from day to day and with minor changes in the clinical status. The ptdmbnary second sound is usually moderately accentuated, and the aortic second sound is generally normal. Signs of congestive heart failure are dramatic, and there is often marked generalized edema and hepatomegaly. Despite the left-sided heart involvement, pulmonary edema is uncommon. Fluoroscopic and Roentgen Findings: The heart is grossly enlarged, and routinely the cardio:thoracic ratio is between 60 and 75 per cent or greater. The most striking characteristic of the fluoroscopy is that there is minimal evidence of volume alteration between systole and diastole. A quiet heart is seen although the distinctive features of individual chambers are retained, and there should be little confusion between this heart and the silhouette of pericardial effusion. The left ventricle and left atrium are grossly dilated and inactive. The lungs are usually remarkably clear, although there may be evidence of pulmonary venous congestion. Compression ateleetasis of the lower lobe of the left lung is not uncommon. The Electrocardiogram: The electrocardiogram in this syndrome is strik-
174
MANNING AND KEITH
ing and serves as a major differential point from other causes of primary myocardial failure in infancy and childhood. It is characterized by a marked left ventrieular hypertrophy pattern of increased voltage and flattened or inverted T waves over the left precordial leads. This hypertrophy pattern is generally one of a tall R wave in lead V6 exceeding 20 mm. and a deep S wave in V1 of greater than 20 ram. The electrical axis in the frontal plane may remain essentially normal or may shift slightly to the left. The direction of the frontal loop is almost routinely clockwise. When one is confronted with the problem of primary myocardial disease, particularly when the onset is under the age of 2 years, the period of greatest frequency of primary endoeardial fibroelastosis, this pattern is strikingly characteristic), 17,18 Hemodynamics: Most patients have not been subjected to hemodynamic studies. When done, usually after initial clinical stabilization, they have shown elevation of pulmonary artery and pulmonary wedge pressures. The end-diastolic pressure of the left ventricle has been elevated. Cardiac output is low and stroke volume diminished2 s,19 Angiocardiography: Angioeardiographic studies have shown poor systolic emptying of the left ventricle with retention of dye in the left side of the heart and evidence of a small stroke volume2 s,19 Some authors have emphasized these findings as quite characteristic for the disease. 1s,1~ Our experience would agree with this, but we would not feel that in most eases it was a necessary adjunct to diagnosis. Endocardial Biopsy: We do not feel that at the present time this procedure justifies its risk. However, it has been used to confirm the pathologic histology, both at operation and by punch biopsy, in patients doing well on medical management?, 21 Skin Test: Recent observations have raised the possibility that the mumps skin test may be of diagnostic value in primary endocardial fibroelastosis, 22 particularly under the age of 2 years. In our experience at the present time, results may be variable. However, our present feeling is that a positive mumps skin test in the first 2 years of life is strong supportive evidence if the rest of the clinical picture is present. A negative mumps skin test result during this period appears to be evidence against the diagnosis. The meaning of this observation is not clear. There has been no history of clinical mumps in either the infants or in their parents or families. Whether this represents a skin reaction to one of the other viruses of the myxovirus group or whether this is a nonspeeifie antigen response, remains to be seen. Method of Management: It is our opinion based on our clinical experience over the past 10 years that with vigorous and sustained medical management, approximately 75 per cent of patients with the clinical diagnosis of primary endoeardial fibroelastosis will survive. Furthermore, nearly 80 per cent of these survivors will revert to a status with an essentially normal heart s~ze and a normal electrocardiogram and will be maintained symptom-free without digitalis therapy. 4
FIBIAOELASTOSISIN CHILDBEN
175
Vigorous and sustained medical m a n a g e m e n t to us means standard presentday methods of decongestive therapy. Using a route of digitalis administration appropriate to the severity of the clinical state, most have been digitalized with between 60 and 80 ~g. o[ Digoxin per Kg. M a ~ t e n a n c e dosage, divided into 2 daily doses, has been between 12 and 25 ~g. of Digoxin per Kg. W h e n necessary, these patients have been supported with oxygen, diuretics, and low salt diet; and they have been subjected to extremely careful longterm medical supervision. 4,a4,18 Experience with steroids and revascularization technics 2a has in general been unsatisfactory TM and at present neither appears to have a substantial place in therapy. A brief summary of our feelings and experience in regard to medical management is as follows. 1. In general, prognosis is better in patients with a subacute or chronic type of onset o~ symptomatology, although 50 per cent of patients presenting with an acute or fulminating onset can be saved. 2. The initial response to therapy is a good index to long-term prognosis. Most deaths occur within the first 2 months of medical management, and most good clinical results will show a significant decrease in heart size during this period. 3. Approximately 70 per cent of good results will have a cardio:thoracic ratio below 55 per cent by the end of 2 years of therapy. 4. Approximately tile same per cent of good results will show a normal electrocardiogram between 2 and 5 years after the onset of therapy.
Duration of Therapy: In general, these patients have required between 3 and 5 years of digitalis therapy. W e have not discontinued digitalis in patients whose cardio:thoracic ratio remained above 55 per cent. We have not discontinued digitalis in a symptomatic patient. Our general policy is to stop therapy gradually, u n d e r careful medical supervision, 2 years after the end of all symptoms, with stabilization of the cardio:thoracic ratio below 55 per cent, and the reversion of the electrocardiogram, including the left ventricular T waves, to a normal state. Differential Diagnosis: A brief review of the more common and difficult problems in differentiai diagnosis with a r6sum6 of major differential points is as follows. 1. Acute myocarclitis: Associated with present or preceding specific infection. Other than epidemic Coxsackie myocarditis of the new born period, age of onset is scattered throughout pediatric age range, rather than concentrated in infantile period. EKG rarely shows hypertrophy patterns and is more likely to show bizarre conduction defects, low voltage QtlS, and S-T segment abnormalities.3,17,is 2. Idiopathic or familial myocardial hypertrophy. Uncommonly display high voltage left ventricular hypertrophy pattern. Unlikely to present as dilated, hypodynamic left side of the heart. In general, do not present in infancy in congestive heart failure. Mode of difficulties and death more likely sudden arrhythmia. 3. Chronic anemic heart disease: May present with identical EKG, however, they have evidence of major anemia. Heart is hyperdynamic and high output in character, rather than hypodynamic and low output. Rapid response to repair of anemia in terms of cardiac reserve although cardiomegaly and electrocardiographic changes persist. Flow murmurs present.
176
MANNING AND KEITH
4. Anomalous origin o~ left coro,mry artery: Age of onset of symptoms usually between ages 2 and 4 months. EKG shows pattern of anterolateral myocardial infarction, rarely a high voltage hypertrophy pattern. When in doubt, coronary angiography can confirm or exclude diagnosis.14,15,18,z4 5. Glycogen storage disease of the heart: Usually show general muscle involvement. Muscle biopsy should be diagnostic. EKG rarely shows more than minimal hypertrophy pattern. No present evidence of survivors past infancy. 6. Secondary Endocardial Fibroelastasis or fibroelastosis associated with significant valvular or other left-sided heart obstructive lesions': Difficult to fully differentiate. Hemodynamic significance (murmurs, etc.) of anatomic lesions may be clue. Severe electrocardiographic changes with lesser evidence of hemodynamic significance may be clue to combined lesion.
The above 6 have been our basic troublemakers. Many other entities have been mentioned in differential diagnosis, but we exclude them by their specific diagnostic characteristics or, occasionally, by rarity. They include idiopathic calcification of coronary arteries, systemic hypertension, paroxysmal tachycardias, cardiac involvement in generalized neuromuscular disease, and acute pericarditis. It should be remembered that primary endocardial fibroelastosis is far more common as a cause of infantile congestive heart failure than any of the above-mentioned entities. The mumps skin test result appears to be negative in all of these including secondary endocardial fibroelastosis. General Comments: Any discussion of the clinical syndrome of primary endocardial fibroelastosis remains unsatisfactory in the void of etiologic knowledge and the absence of definition that this is a specific syndrome with a specific cause. Furthermore, any objective review of an analysis of medical management in this syndrome must take into account the reluctance of many workers to accept the validity of clinical diagnosis, r,l~ Despite this, we would reiterate the view that the diagnostic criteria, when taken as a group, are highly specific2,18 Edwards 25 and Lynfield19 divide patients into a type I, characterized by a dilated left side of the heart, and type II, characterized by a normal or contracted left side of the heart. In our experience, 'the clinical syndrome so regularly associated with fibroelastosis and recognizable by the criteria discussed here, is almost uniformly type I. We, as do others, TM find type II hearts associated with major congenital cardiac anomalies. Such a review as this raises more questions than it answers. In addition to those already reviewed, we might cite the following. The mechanism of response to therapy has not been defined. The fate of the pathologic endocardium in surviving patients is unknown. Long-term hemodynamic observations and the long-term natural history of these patients after medical stabilization need to be documented. Until these gaps have been filled, the consideration of fibroelastosis must remain descriptive and somewhat speculative. All we can really do at the
177
FIBROELASTOSIS IN CHILDBEN
present time is to point out that a body of experience exists which allows us to clinically define a major segment of the clinical spectrum. Furthermore, our experience in clinical management has led us to the definition of a reasonably good prognosis for survival and stability with vigorous and sustained medical management. REFERENCES 1. Weinberg, T., and Himelfarb, A. J.: Endocardial fibroelastosis. Bull. Johns Hopkins Hosp. 72:299, 1943. 2. Anderson, D. H., and Kelly, J.: Endocardial fibroelastosis: 1. Endocardial fibroelastosis associated with cong e n i t a l malformations of the heart. Pediatrics 18:513, 1956. 3. Sellers, F. J., Keith, J. D., and Manning, J. A.: Diagnosis of primary endocardial fibroelastosis. Circulation 29:49, 1964. 4. Manning, J. A., Sellers, F. J., Bynum, R. S., and Keith, J. D.: Medical management of clinical endocardial fibroelastosis. Circulation 29:60, 1964. 5. Still, W. J. S.: Endocardial fibroelastosis. Am. Heart J. 61:579, 1961. 6. Black-Schaffer, B.: Infantile endocardial fibroelastosis. Arch. Path. 63:281, 1957. 7. Lambert, E. C., and Vlad, P.: Primary endomyocardial disease. Pediat. Clin. North America 1958. 8. Gross, P.: Concept of fetal endocarditis: a general review with report of an illustrative case. Arch. Path. 31:163, 1941. 9. Miller, A. J., Pick, R., and Katz, L. N.: Ventricular endomyocardial pathology following chronic impairment of cardiac lymph flow in the dog. Brit. Heart J. 25:182, 1963. 10. Johnson, F. R.: Anoxia as a cause of endocardial fibroelastosis in infancy. Arch. Path. 54:237, 1952. 11. Blumberg, R. W., and Lyon, R. A.: Endocardial sclerosis. Am. J. Dis. Child. 84:291, 1952. 12. Auld, W. H. g., and Watson, H.: Fibroelastosis of the heart in adolescence. Brit. Heart J. 19:186, 1957. 13. Thomas, W. A., Randall, R. V., Bland, E. F., and Castleman, B.: Endocardial fibroelastosis: A factor in heart
14.
15.
16.
17.
18.
191
20.
21.
22.
23.
disease of obscure etiology: a study of 20 autopsied cases in children and adults. New Eng. J. Med. 251:327, 1954. Keith, J. D., Rowe, R. D., and Vlad, P.: Heart Disease in Infancy and Childhood. New York, Macmillan Co., 1958. Nadas, A. S.: Pediatric Cardiology. Philadelphia, W. B. Saunders Co., 1963, p. 272. Dennis, J. L., Hansen, A. E., and Corpening, T. N.: Endocardial fibroelastosis. Pediatrics 12:130, 1953. Vlad, P., Rowe, R. D., and Keith, J. D.: The electrocardiogram in primary endocardial fibroelastosis. Brit. Heart J. 17:189, 1955. Linde, L. M., and Adams, F. H.: Prognosis in endocardial fibroelastosis. J. Dis. Child. 105:329, 1963. Lynfield, ]., Gasul, B. M., Luan, L. L., and Dillon, R. F.: Right and left heart catheterization and angioeardiographie findings in idiopathic cardiac hypertrophy with endocardial flbroelastosis. Circulation 21: 386, 1960. Linde, L. M., Adams, F. H., and O'Loughlin, J. J.: Endocardial fibroelastosis: angiocardiographic studies. Circulation 17:40, 1958. D~court, L. V., Maeruz, R., Carcia, D. P., and Todoni, H.: Endocardial fibroelastosis: its study by punch-biopsy of the heart. Fourth World Congress of Cardiology, Mexico City, 1962. Noren, G. R., Adams, P., and Anderson, R. C.: Positive skin reactivity to mumps virus antigen in endocardial fibroelastosis. J. Pediat. 62:604, 1963. Paul, R. N., and Bobbins, S. C.: Surgical treatment for endocardial flbroelastosis or anomalous left coronary artery. Am. J. Cardiol. 1:694, 1958.
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178 24. Sabiston, D. C., Jr., Neill, C. A., and Taussig, H. B.: The direction of blood flow in anomalous left coronary artery arising from the pulmonary artery. Circulation 22:591, 1960.
James A.
Manning,
25. Edwards, J. E.: Congenital malformations of the heart and great vessels. In Gould, S. E.: Pathology of the Heart. Springfield, Ill., Charles C Thomas, 1953, p. 266,
M.D., Strong Memorial Rochester, N. Y.
Hospital,
]ohn D. Keith, M.D., The Hospital for Sick Children, Toronto, Ontario.