- Email: [email protected]
Eosinophilic heart disease
TRANSACTIONS OF THE ROYALSOCIETY OF TROPICAL MHDIWNE ANDHYGIENE,VOL. 77, No. 1, 2-4 (1983) ROYAL
SOCIETY
OF TROPICAL
Ordinary Manson
House,
MEDICINE
AND
HYGIENE
Meeting 18th March,
1982
The President, Dr. A. J. DUCGAN in the Chair
Eosinophilic
heart disease
E. G. J. OLSEN National
Heart Hospital,
Westmoreland Street, London WlM
Endomyocardial diseasein association with eosinophilia is included under the term cardiomyopathy, defined as heart muscle disease of unknown cause, and is classified among the restrictive types of cardiomyopathy (WHO/‘ISFC*, 1980).(The other two types are dilated and hypertrophic cardiomyopathies.) Tropical endomyocardial disease (endomyocardial fibrosis) and eosinophilic endomyocardial disease (LBffler’s endocarditis parietalis fibroplastica) (LbFFLER, 1936) are included under the term “restrictive cardiomyopathies”. These diseaseswere thought for a long time to be separate entities. Tropical endomyocardial disease
The pathology of this condition, which is also known as tropical endomyocardial fibrosis, was first described by DAVIES (1948) and subsequently from the same Institute by SHAPERet al., 1968. Most commonly, both ventricles are involved (51%) but lone right ventricular (11%) and left ventricular involvement (38%) can occur. The striking feature at post-mortem is the endocardium which is extremely thickened and, in left ventricular involvement, the inflow tract, apex and part of the outflow tract are frequently affected (OLSEN,1975).When the region of the anterior mitral valve leaflet is reached, the-thick endocardium ends abrumlv in a thick rolled edee (DAVIES. 1968). In righ
8BA
connective tissue in which dilated blood vessels are embedded as well as varying degreesof inflammatory cells, occasionally including eosinophils. The myocardium shows the changes of hypertrophy, but some degenerative changesmay be observed adjacent to the septa. The small intramyocardial vesselsshow occasional non-specific intimal thickening. Eosinopkilic endomyocardial disease
This condition was described by L~FFLER (1936) and despite several communications on reputed differences there are no changes from those observed in tropical endomyocardial d&ease at macroscopic and histological level and indeed clinically, except that a definite link with eosinopbilia has been established. The Unitarian theory
It had been believed that tropical endomyocardial disease was confined to the tropics and certain subtropical regions, whereas eosinophilic endomyocardial disease was found in temperate zones. Several vears aeo BROCKINGTON & OLSEN (1973') communicated with authors who had published cases of eosinophilia and heart disease. Provided that tbe patients described in these communications had a full post-mortem examination we included them in our review. We were able to collect data on some90 cases. Pathology was also available in a number of cases.The causeof eosinophilia varied; in most no causecould be identified and the eosinophilia was therefore classified as idiopathic. When association with polyarteritis nodosa, parasites or tumour could be established, these patients were included under the term reactive eosinophilia. The third group was of patients with eosinophilic leukaemia but most of these probably belonged to the idiopathic group. As far as the pathological material was concerned three major stagescould be identified which depended on the length of time these patients had suffered from the disease before death. The necrotic phase was reached when the patient survived for an averageof 5.5 weeks. Pathologically, an intense myocarditis, rich in eosinophils was observed, limited usually to the inner rims of the ventricular walls. When the patients survived for an
E. G. J. OLSEN
average of 10 months the thrombotic stage was reached. At this stage some endocardial thicket&a and varying degrees of thrombus superimposition which, in extreme cases, totally obliterated the involved ventricular cavity was noted. The fibrotic stage was reached when the patient survived on averagefor 24.5 months and at this late stage thick fibrous endocardium, arranged in layers, was found. 16 caseswere in tlus stage. These cases were compared with tissue from patients diagnosed as tropical endomyocardial disease,obtained from Uganda, Brazil and Nigeria and various measurementsand morphometric techniques were performed. No difference between the fibrotic stage of eosinophilic endomyocardial disease and that of tropical endomyocardial disease could be established. We concluded that both these entities belong to the same disease spectrum, the origin of which could be traced back to the presence of eosinophils in the myocardium (BROCKINGTON& OLSEN. 1973). In a study of patients with eosinophilic endomyocardial diseaseit was noted that many of the blood eosinophils were morphologically abnormal (SPRY & TAI, 1976). Subsequentwork has shown that this involves both vacuolation (which is non-specific) and degranulation. It was found that if over 15% (1 X 109/litre) of eosinophils were degranulated, endomyocardial disease is associated (OLSEN & SPRY, 1979). It has also been found that the binding capacity of eosinophils for complexed IgG and increased phagocytosis takes place with unmasking Fc receptors. Degranulation occurs as a result of binding to IgG or C3b coated particles or parasites(MCLAREN et aE., 1978). Electron microscopic examination has shown that the granules are consistent with the appearance of cationic proteins. These proteins, possibly in combination with peroxidases or other toxic substances, result in myocarditis with subsequent thrombosis which leads to the established fibrous changesof endomyocardial disease.This work has been carried out on patients from the temperate zones and modern treatment is directed towards the reduction of cationic proteins in the blood stream which are significantlv raised in affected natients. When the fib
3
tropical endomycardial disease and eosinophilic endomyocardial disease (BROCKINGTON & OLSEN, 1973; BELL et al., 1976). One of the differences,
morphologically, that has been consistently cited is changes in intramyocardial vessels, an arteritis being found (WEISS-CARMINE,1957). It has been established that in the acute stagesof the diseaseprocess, irrespective of the geographical origin of the patients, an arteritis is present which, in the thrombotic stage, is characterized by thrombi within the lumina of the small vessels.When the fibrotic stageis reached, these thrombi are incorporated into the vesselwalls and can be recognized as non-specific intimal thickening (OLSEN & SPRY, 1979). There is therefore ample evidence that tropical and eosinophilic endomyocardial disease belong to the samediseasespectrum. Work is at present in progress examining the eosinophils from patients in southern India. If it can be established that these patients also show degranulation of their eosinophils, then the link between the tropical disease and that seen in the temperate zones is fully established and then, according to the definition, this type of cardiomyopathy would be removed from the classification. It could be argued that reports of eosinophilia in patients with endomyocardial diseasefrom the tropical zones are infrequent but it could be that when patients first come under medical supervision, they are in the late stages of the disease and thus the necrotic and thrombotic phases may go undetected (OLSEN & SPRY, 1979). To stimulate awarenessof the association of abnormal eosinophils to endomvocardial diseaseis one of the aims that we hope to achieve during the vear 1982. which has been declared the Year ‘bf Tropical Cardiology by the International Society and Federation of Cardiology. References Bell. I. A.. lenkins. B. S. & Webb-Penloe. M. M. (1976). Cl&al “haemodynamic and angiography findings in Loffler’s endocarditis. British HeartJournal, 38,541-548. Brockington, I. F. & Olsen, E. G. J. (1973). Loffler’s endocarditis and Davies’ endomyocardial fibrosis. American Heart Journal,
85, 308-322.
Connor, D. H., Somers, K., Hutt, M. S. R., Manion, W. C. & D’Arbela, P. G. (1967). Endomyocardial fibrosis in Uganda (Davies’ disease)An epidemiologic, clinical and g;F;lo9gic study. Part I. Amcan Heart 3ourna1,74, Connor, D.‘H., Somers, K., Hun, M. S. R., Manion, W. C. & D’Arbela, P. G. (1968). Endomyocardial fibrosis in Uganda (Davies’ disease)An epidemiologic, clinical and pathologic study. Part II. American Heart 3owna1,75, 107-124. Davies, J. N. P. (1948). Endomyocardial necrosis. A heart disease of obscure aetiology. MD. Thesis, Bristol. Davies, J. N. P. (1968). The ,ridge in endomyocardial fibrosis. Lancer, i, 631-632. Davies, J., Sapsford, R., Brooksby, I., Olsen, E. G. J., Spry, C. J. F., Oakley, C. M., & Goodwin, J. F. (1981). Successful surgical treatment of two patients with eosinophilic endomyocardial disease.British Heart Journal, 46, 438-445.
Loffler, W. (1936). Endocarditis parietalis fibroplastica mit Bluteosinophilie. Ein eigenartiges Krankheitsbild. Schweiztische Medizinische Wochenschrift, 18, 817-820. McLaren, D. J., Ramalho-Pinto, F. J. & Smithers, D. J. (1978). Ultrastructural evidence for complement and antibody-dependent damage to schistosomula of Schisro-
4
ROYAL
SOCIETY
OF
TROPICAL
MEDICINE
somnmansoniby rat eosinophils in vitro. Parasitology, 77, 313-324. Pate& A. K., D’Arbela, P. G. & Somers, K. (1977). Endomyocardial fibrosis and eosinophilia. British Heart Journal, 39, 238-241. Olsen, E. C. J. (1972). Cardiomyopathies. Cardiovascular Clinics, 4, 240-261. Olsen, E. C. J. (1975). Pathological recognition of cardiomyopathy. Postgraduate MedicalJournal, 51,277-281. Olsen, E. C. J. & Spry, C. J. F. (1979). The pathogenesisof Loffler’s endomyocardial disease, and its relationship to endomyocardial fibrosis. In: Progressin Cardiology, Vol. 8. Yu, P. N. & Goodwin, J. F. (Editors). Philadelphia: Lea & Febiger, pp. 281-303. Shaper, A. G., Hutt, M. S. R. & Coles, R. M. (1968). Necropsy studies of endomyocardial fibrosis and rheumatic heart diseasein Uganda. British HeartJournal, 30, 391-401. Spry, C. J. F. & Tai, P. C. (1976). Studies on blood eosinophils. II. Patients with Loffler’s cardiomyopathy. Clinical and Experkntal
Immunology, 24, 423-434.
Weiss-Carmine, S. (1957). Die Endocarditis parietalis fibroplastica mit Bluteosinophilie (Loffler) und ihre Stellung im Rahmen der Parietalendokardfibrosen. Schweizerische Medizinische Wochenschtiji, 87, 890-898.
WHO/ISFC (1980). Report of the WHO/ISFC Task Force on the Definition and Classification of Cardiomyopathies. British Heart Jounurl, 44, 672-673. Appendix The Year of Tropical Cardiology
1982was declared the Year of Tropical Cardiology by the International Society and Federation of Cardiology (ISFC) in collaboration with the World Health Oreanixation (WHO). The ISFC is the amalgamation of two $reviously ‘existing separate international bodies, namely the International Society of Cardiology and the International Cardiology
AND
HYGIENE-RDINARY
MEETING
Federation. The amalgamation was ratified at the World Congress of Cardiology in Tokyo in September 1978. The membership of the ISFC consists of 61 countries, either through their Cardiac Societies and/or Heart Foundations. The scientific aspects are dealt with by nine Scientific Councils and these are: Atherosclerosis, Cardiac Metabolism, Cardiomyopathies, Clinical Cardiology, Epidemiology and Prevention, Hypertension, Paediatric Cardiology, Rehabilitation of Cardiac Patients and Thrombosis and Haemostasis.Each Council consistsof a Chairman and up to 20 experts, elected from all parts of the world. The aims during 1982were to create awarenessof concern, particularly in the under-developed countries. We also hope that we drew attention to local and national cardiac disease and stimulated a systematic approach to the study of heart disease.Medical as well as lay education played an important role throughout the year with emphasis on prevention. This was achieved through University Hospitals organizing symposia, emphasizing cardiovascular diseasesprevalent in their area and staff from these hospitals visiting outlying nonteaching hospitals. In addition it was hoped that paramedical staff could be brought up to date. It was also hoped that during 1982national Cardiac Society meetings would devote at least part of their meetings to the problems of cardiovascular diseasesseen in the tropics, which could also include those diseases seen thoughout the world. There were International meetings in South America and in Africa, as well as in India, and a session during the Congress and a Satellite meeting immediately following the World Congress of Cardiology in Moscow in June 1982 took place. We also hope to have stimulated researchamong centres of individual countries and neighbouring countries and finally to draw attention of governments to urgent needs. The meetina of the Roval Societv of Trouical Medicine and Hygiene was an excellent example of the type of topics and discussions of immense value during 1982, which was devoted to tropical cardiology.
SOCIETY
OF TROPICAL
Ordinary Manson
House,
MEDICINE
AND
HYGIENE
Meeting 18th March,
1982
The President, Dr. A. J. DUCGAN in the Chair
Eosinophilic
heart disease
E. G. J. OLSEN National
Heart Hospital,
Westmoreland Street, London WlM
Endomyocardial diseasein association with eosinophilia is included under the term cardiomyopathy, defined as heart muscle disease of unknown cause, and is classified among the restrictive types of cardiomyopathy (WHO/‘ISFC*, 1980).(The other two types are dilated and hypertrophic cardiomyopathies.) Tropical endomyocardial disease (endomyocardial fibrosis) and eosinophilic endomyocardial disease (LBffler’s endocarditis parietalis fibroplastica) (LbFFLER, 1936) are included under the term “restrictive cardiomyopathies”. These diseaseswere thought for a long time to be separate entities. Tropical endomyocardial disease
The pathology of this condition, which is also known as tropical endomyocardial fibrosis, was first described by DAVIES (1948) and subsequently from the same Institute by SHAPERet al., 1968. Most commonly, both ventricles are involved (51%) but lone right ventricular (11%) and left ventricular involvement (38%) can occur. The striking feature at post-mortem is the endocardium which is extremely thickened and, in left ventricular involvement, the inflow tract, apex and part of the outflow tract are frequently affected (OLSEN,1975).When the region of the anterior mitral valve leaflet is reached, the-thick endocardium ends abrumlv in a thick rolled edee (DAVIES. 1968). In righ
8BA
connective tissue in which dilated blood vessels are embedded as well as varying degreesof inflammatory cells, occasionally including eosinophils. The myocardium shows the changes of hypertrophy, but some degenerative changesmay be observed adjacent to the septa. The small intramyocardial vesselsshow occasional non-specific intimal thickening. Eosinopkilic endomyocardial disease
This condition was described by L~FFLER (1936) and despite several communications on reputed differences there are no changes from those observed in tropical endomyocardial d&ease at macroscopic and histological level and indeed clinically, except that a definite link with eosinopbilia has been established. The Unitarian theory
It had been believed that tropical endomyocardial disease was confined to the tropics and certain subtropical regions, whereas eosinophilic endomyocardial disease was found in temperate zones. Several vears aeo BROCKINGTON & OLSEN (1973') communicated with authors who had published cases of eosinophilia and heart disease. Provided that tbe patients described in these communications had a full post-mortem examination we included them in our review. We were able to collect data on some90 cases. Pathology was also available in a number of cases.The causeof eosinophilia varied; in most no causecould be identified and the eosinophilia was therefore classified as idiopathic. When association with polyarteritis nodosa, parasites or tumour could be established, these patients were included under the term reactive eosinophilia. The third group was of patients with eosinophilic leukaemia but most of these probably belonged to the idiopathic group. As far as the pathological material was concerned three major stagescould be identified which depended on the length of time these patients had suffered from the disease before death. The necrotic phase was reached when the patient survived for an averageof 5.5 weeks. Pathologically, an intense myocarditis, rich in eosinophils was observed, limited usually to the inner rims of the ventricular walls. When the patients survived for an
E. G. J. OLSEN
average of 10 months the thrombotic stage was reached. At this stage some endocardial thicket&a and varying degrees of thrombus superimposition which, in extreme cases, totally obliterated the involved ventricular cavity was noted. The fibrotic stage was reached when the patient survived on averagefor 24.5 months and at this late stage thick fibrous endocardium, arranged in layers, was found. 16 caseswere in tlus stage. These cases were compared with tissue from patients diagnosed as tropical endomyocardial disease,obtained from Uganda, Brazil and Nigeria and various measurementsand morphometric techniques were performed. No difference between the fibrotic stage of eosinophilic endomyocardial disease and that of tropical endomyocardial disease could be established. We concluded that both these entities belong to the same disease spectrum, the origin of which could be traced back to the presence of eosinophils in the myocardium (BROCKINGTON& OLSEN. 1973). In a study of patients with eosinophilic endomyocardial diseaseit was noted that many of the blood eosinophils were morphologically abnormal (SPRY & TAI, 1976). Subsequentwork has shown that this involves both vacuolation (which is non-specific) and degranulation. It was found that if over 15% (1 X 109/litre) of eosinophils were degranulated, endomyocardial disease is associated (OLSEN & SPRY, 1979). It has also been found that the binding capacity of eosinophils for complexed IgG and increased phagocytosis takes place with unmasking Fc receptors. Degranulation occurs as a result of binding to IgG or C3b coated particles or parasites(MCLAREN et aE., 1978). Electron microscopic examination has shown that the granules are consistent with the appearance of cationic proteins. These proteins, possibly in combination with peroxidases or other toxic substances, result in myocarditis with subsequent thrombosis which leads to the established fibrous changesof endomyocardial disease.This work has been carried out on patients from the temperate zones and modern treatment is directed towards the reduction of cationic proteins in the blood stream which are significantlv raised in affected natients. When the fib
3
tropical endomycardial disease and eosinophilic endomyocardial disease (BROCKINGTON & OLSEN, 1973; BELL et al., 1976). One of the differences,
morphologically, that has been consistently cited is changes in intramyocardial vessels, an arteritis being found (WEISS-CARMINE,1957). It has been established that in the acute stagesof the diseaseprocess, irrespective of the geographical origin of the patients, an arteritis is present which, in the thrombotic stage, is characterized by thrombi within the lumina of the small vessels.When the fibrotic stageis reached, these thrombi are incorporated into the vesselwalls and can be recognized as non-specific intimal thickening (OLSEN & SPRY, 1979). There is therefore ample evidence that tropical and eosinophilic endomyocardial disease belong to the samediseasespectrum. Work is at present in progress examining the eosinophils from patients in southern India. If it can be established that these patients also show degranulation of their eosinophils, then the link between the tropical disease and that seen in the temperate zones is fully established and then, according to the definition, this type of cardiomyopathy would be removed from the classification. It could be argued that reports of eosinophilia in patients with endomyocardial diseasefrom the tropical zones are infrequent but it could be that when patients first come under medical supervision, they are in the late stages of the disease and thus the necrotic and thrombotic phases may go undetected (OLSEN & SPRY, 1979). To stimulate awarenessof the association of abnormal eosinophils to endomvocardial diseaseis one of the aims that we hope to achieve during the vear 1982. which has been declared the Year ‘bf Tropical Cardiology by the International Society and Federation of Cardiology. References Bell. I. A.. lenkins. B. S. & Webb-Penloe. M. M. (1976). Cl&al “haemodynamic and angiography findings in Loffler’s endocarditis. British HeartJournal, 38,541-548. Brockington, I. F. & Olsen, E. G. J. (1973). Loffler’s endocarditis and Davies’ endomyocardial fibrosis. American Heart Journal,
85, 308-322.
Connor, D. H., Somers, K., Hutt, M. S. R., Manion, W. C. & D’Arbela, P. G. (1967). Endomyocardial fibrosis in Uganda (Davies’ disease)An epidemiologic, clinical and g;F;lo9gic study. Part I. Amcan Heart 3ourna1,74, Connor, D.‘H., Somers, K., Hun, M. S. R., Manion, W. C. & D’Arbela, P. G. (1968). Endomyocardial fibrosis in Uganda (Davies’ disease)An epidemiologic, clinical and pathologic study. Part II. American Heart 3owna1,75, 107-124. Davies, J. N. P. (1948). Endomyocardial necrosis. A heart disease of obscure aetiology. MD. Thesis, Bristol. Davies, J. N. P. (1968). The ,ridge in endomyocardial fibrosis. Lancer, i, 631-632. Davies, J., Sapsford, R., Brooksby, I., Olsen, E. G. J., Spry, C. J. F., Oakley, C. M., & Goodwin, J. F. (1981). Successful surgical treatment of two patients with eosinophilic endomyocardial disease.British Heart Journal, 46, 438-445.
Loffler, W. (1936). Endocarditis parietalis fibroplastica mit Bluteosinophilie. Ein eigenartiges Krankheitsbild. Schweiztische Medizinische Wochenschrift, 18, 817-820. McLaren, D. J., Ramalho-Pinto, F. J. & Smithers, D. J. (1978). Ultrastructural evidence for complement and antibody-dependent damage to schistosomula of Schisro-
4
ROYAL
SOCIETY
OF
TROPICAL
MEDICINE
somnmansoniby rat eosinophils in vitro. Parasitology, 77, 313-324. Pate& A. K., D’Arbela, P. G. & Somers, K. (1977). Endomyocardial fibrosis and eosinophilia. British Heart Journal, 39, 238-241. Olsen, E. C. J. (1972). Cardiomyopathies. Cardiovascular Clinics, 4, 240-261. Olsen, E. C. J. (1975). Pathological recognition of cardiomyopathy. Postgraduate MedicalJournal, 51,277-281. Olsen, E. C. J. & Spry, C. J. F. (1979). The pathogenesisof Loffler’s endomyocardial disease, and its relationship to endomyocardial fibrosis. In: Progressin Cardiology, Vol. 8. Yu, P. N. & Goodwin, J. F. (Editors). Philadelphia: Lea & Febiger, pp. 281-303. Shaper, A. G., Hutt, M. S. R. & Coles, R. M. (1968). Necropsy studies of endomyocardial fibrosis and rheumatic heart diseasein Uganda. British HeartJournal, 30, 391-401. Spry, C. J. F. & Tai, P. C. (1976). Studies on blood eosinophils. II. Patients with Loffler’s cardiomyopathy. Clinical and Experkntal
Immunology, 24, 423-434.
Weiss-Carmine, S. (1957). Die Endocarditis parietalis fibroplastica mit Bluteosinophilie (Loffler) und ihre Stellung im Rahmen der Parietalendokardfibrosen. Schweizerische Medizinische Wochenschtiji, 87, 890-898.
WHO/ISFC (1980). Report of the WHO/ISFC Task Force on the Definition and Classification of Cardiomyopathies. British Heart Jounurl, 44, 672-673. Appendix The Year of Tropical Cardiology
1982was declared the Year of Tropical Cardiology by the International Society and Federation of Cardiology (ISFC) in collaboration with the World Health Oreanixation (WHO). The ISFC is the amalgamation of two $reviously ‘existing separate international bodies, namely the International Society of Cardiology and the International Cardiology
AND
HYGIENE-RDINARY
MEETING
Federation. The amalgamation was ratified at the World Congress of Cardiology in Tokyo in September 1978. The membership of the ISFC consists of 61 countries, either through their Cardiac Societies and/or Heart Foundations. The scientific aspects are dealt with by nine Scientific Councils and these are: Atherosclerosis, Cardiac Metabolism, Cardiomyopathies, Clinical Cardiology, Epidemiology and Prevention, Hypertension, Paediatric Cardiology, Rehabilitation of Cardiac Patients and Thrombosis and Haemostasis.Each Council consistsof a Chairman and up to 20 experts, elected from all parts of the world. The aims during 1982were to create awarenessof concern, particularly in the under-developed countries. We also hope that we drew attention to local and national cardiac disease and stimulated a systematic approach to the study of heart disease.Medical as well as lay education played an important role throughout the year with emphasis on prevention. This was achieved through University Hospitals organizing symposia, emphasizing cardiovascular diseasesprevalent in their area and staff from these hospitals visiting outlying nonteaching hospitals. In addition it was hoped that paramedical staff could be brought up to date. It was also hoped that during 1982national Cardiac Society meetings would devote at least part of their meetings to the problems of cardiovascular diseasesseen in the tropics, which could also include those diseases seen thoughout the world. There were International meetings in South America and in Africa, as well as in India, and a session during the Congress and a Satellite meeting immediately following the World Congress of Cardiology in Moscow in June 1982 took place. We also hope to have stimulated researchamong centres of individual countries and neighbouring countries and finally to draw attention of governments to urgent needs. The meetina of the Roval Societv of Trouical Medicine and Hygiene was an excellent example of the type of topics and discussions of immense value during 1982, which was devoted to tropical cardiology.