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Endomyocardial Fibrosis: Still a Mystery after 60 Years

  • Gene Bukhman ,

    Affiliation Division of Social Medicine and Health Inequalities, Brigham and Women's Hospital, Boston, Massachusetts, United States of America

  • John Ziegler,

    Affiliation Cancer Risk Program, University of California San Francisco, San Francisco, California, United States of America

  • Eldryd Parry

    Affiliation Clinical Research Unit, London School of Hygiene & Tropical Medicine, London, United Kingdom

Endomyocardial Fibrosis: Still a Mystery after 60 Years

  • Gene Bukhman, 
  • John Ziegler, 
  • Eldryd Parry


The pathologist Jack N. P. Davies identified endomyocardial fibrosis in Uganda in 1947. Since that time, reports of this restrictive cardiomyopathy have come from other parts of tropical Africa, South Asia, and South America. In Kampala, the disease accounts for 20% of heart disease patients referred for echocardiography. We conducted a systematic review of research on the epidemiology and etiology of endomyocardial fibrosis. We relied primarily on articles in the MEDLINE database with either “endomyocardial fibrosis” or “endomyocardial sclerosis” in the title. The volume of publications on endomyocardial fibrosis has declined since the 1980s. Despite several hypotheses regarding cause, no account of the etiology of this disease has yet fully explained its unique geographical distribution.

September 2007 will mark the 60th anniversary of the description of endomyocardial fibrosis (EMF) in Uganda by the pathologist Jack N. P. Davies [1]. Observed by Arthur Williams as early as 1938, Davies and his colleagues at Makerere University delineated the clinico-pathologic features of this new restrictive cardiomyopathy, still called Davies disease by some [2],[3],[4]. Although virtually unknown outside of the tropics, cases of EMF continue to surface from parts of equatorial Asia and South America where the disease afflicts impoverished children and young adults [5]. The highest prevalence of this condition likely remains, however, in regions of sub-Saharan Africa. As a rough estimate, the burden of EMF may well compare in scope to Chagas cardiomyopathy [6].

Subendocardial fibrosis of the apices and inflow tracts of the right ventricle, left ventricle, or both defines the disease [7],[8]. This restrictive scarring prevents ventricular filling, and tethering of the papillary muscles leads to valvular regurgitation (Figure 1; Video S1). A review of autopsies in Uganda between 1959 and 1969 emphasized the poor prognosis of this condition, with an average survival of 2 y after symptom onset [9]. Later series from Brazil and India found more variability in the course of medically treated patients and echoed findings from southern Nigeria of both acute and chronic forms of the disease [10],[11],[12]. The advent of surgical resection and valvular replacement during the 1970s promised 10-y survival rates as high as 68% for selected patients, but at the price of high peri-operative mortality [13],[14],[15],[16],[17]. Unfortunately, EMF has most affected those regions least equipped with cardiovascular surgery.

Figure 1. Top, echocardiogram in a 25-y-old man with predominantly right ventricular EMF from eastern Rwanda.

Apical four-chamber view. Note the marked dilatation of the right atrium. RV = right ventricle, RA = right atrium, LV = left ventricle, LA = left atrium. Bottom, massive ascites in the same patient.

The question of whether all cases of EMF have the same underlying cause still ranks as one of the great mysteries in cardiology. Does the pathogenesis of this disease result from a single process? Or does EMF represent a common pathway for diverse insults such as those that lead to dilated cardiomyopathies?

Davies himself, who died in 1998 at the age of 83, believed to the end that EMF had a unifying explanation [18]. He thought the clue perhaps lay in the similarity between the heart lesion in EMF and the endocarditis parietalis fibroplastica that Wilhelm Löffler and others had described in Europe in the setting of hypereosinophilic syndromes [19],[20]. The eosinophil hypothesis—dominant though still not well tested—has failed to convince critics who point to other plausible alternatives [21],[22],[23],[24]. In fact, none of the etiologic categories first mentioned by Williams, Ball, and Davies in 1954 have left the table of possible causes (Table 1) [25].

Despite uncertainty as to the cause of EMF, the volume of publications on the subject has declined during the past decade (Figure 2). In an effort to rekindle interest in this neglected disease, we have undertaken a systematic review of research on this condition. We have based this review primarily on articles in the MEDLINE database published between January 1, 1950 and January 1, 2007 with either “endomyocardial fibrosis” or “endomyocardial sclerosis” in the title. We limited this search to articles in English, French, or Spanish and did not search other databases. We consulted additional papers and books referenced through this search strategy, and have cited those most focused on epidemiology and etiology.

Figure 2. Number of publications in MEDLINE between 1950 and 2006 with either “endomyocardial fibrosis” or “endomyocardial sclerosis” in the title.


The clinical manifestations of EMF of either ventricle overlap with other conditions that cause heart failure or ascites. For this reason, a conclusive diagnosis of EMF depends on imaging or surgical visualization of the heart during life, or on autopsy after death [26],[27],[28].

Since the first descriptions of EMF at autopsy in West and East Africans in the late 1940s, over 2,400 cases of the disease have been reported throughout the world [1],[29]. Half of these cases have come from sub-Saharan Africa, and a quarter have come from Uganda alone. Connor and colleagues have questioned the relationship between Ugandan EMF and the West African disease [3]. Other regions with large series include Brazil, Côte d'Ivoire, southern Nigeria, coastal Mozambique, and Kerala State in India (Figure 3). Reporting bias skews this distribution, and in the absence of population-based studies, worldwide prevalence can only be estimated.

Figure 3. Distribution by country of published cases of endomyocardial fibrosis between 1950 and 2006.

Includes only those cases diagnosed at autopsy, or confirmed by surgery or cardiac imaging. Within-country variation depicted for Brazil, China, India, Mozambique, and Nigeria.

The frequency of EMF cases in Uganda has a bimodal peak at age 10 and age 30 [30]. Childhood EMF in this country affects boys and girls equally, while adult EMF affects women twice as often as men [30],[31]. In Nigeria, some studies have found a two to one male preponderance, while others have not shown any difference between the sexes [32].

The majority of EMF cases have come from low-lying, humid parts of tropical countries (Table 2). In East Africa, Uganda has a striking burden of EMF in contrast with Kenya and the Ethiopian highlands. In Tanzania and Mozambique, cases have clustered along the coastal forest [33],[34],[35]. Despite the frequency of EMF in the areas around the southern cities of Ibadan and Enugu in Nigeria, a review of cardiovascular admissions to a referral center in Zaria's northern savanna during the 1970s found no patients with this disease [36],[37],[38],[39]. In India, Kerala's tropical rain forest has generated one of the largest case series in the world, while other parts of the country have reported relatively few cases. In China, the largest number of case reports has also come from the southern province of Guangxi [40]. In South America, patients with EMF have come from Brazil and Columbia rather than Peru or Ecuador.

Table 2. Prevalence of EMF in Africa, Latin America, South Asia, China, and the Middle East.


Theories about the etiology of EMF have tried to explain the condition's unusual geography and pathology. The apparent concentration of EMF in the tropics has led to a search for infectious or nutritional causes. In particular, the similarity of EMF lesions to those in Löffler endocarditis and carcinoid heart disease has suggested a connection with serotonin or eosinophil toxicity.

Unfortunately, research on EMF peaked prior to the diffusion of echocardiography in the much of the tropics [28],[41],[42],[43],[44]. The lack of non-invasive imaging restricted studies to small autopsy or angiocardiographic series [45]. Descriptions of the clinical progression of the disease suffered from lack of diagnostic confirmation as well [12],[46]. Expansion of echocardiographic referral centers and the development of a sub-Saharan heart failure registry will do much to clarify the epidemiology of EMF in this region [47].

At present, only a few investigators have tested the proposed causes of EMF. Early enthusiasm for the role of serotonin in a plantain-based diet waned by the early 1970s [48],[49],[50]. Encouraged at first by the demonstration of high 5-hydroxyindole-acetic acid (5-HIAA) levels in the urine of West and East Africans, this work culminated when McKinney and Crawford fed plantains to guinea pigs, rats, and Patus monkeys [49],[51],[52],[53],[54]. They could not reproduce typical EMF lesions. With the finding that serum 5-hydroxytryptamine (5-HT) levels failed to rise in EMF patients fed a diet of plantains in Nigeria, investigation on this hypothesis ceased [55].

The eosinophil hypothesis gained prominence in the 1960s with reports of eosinophilic endomyocardial disease among European visitors to tropical regions [56],[57],[58],[59],[60],[61]. At the same time, Ive and Brockington in Nigeria found filariasis (onchocerciasis or loiasis) rates approaching 100% among 42 patients with angiographic EMF compared with 44% of 115 controls (p<0.001) [62],[63]. The suggestion that helminth-induced eosinophilia precipitated a tropical variant of the eosinophilic heart disease known as Löffler's found support in later accounts of helminth-associated EMF in natives and visitors to sub-Saharan Africa [64],[65].

The case for the equivalence of end-stage Löffler's and EMF rests on two formal evaluations [31]. The first study, published by Brockington and Olsen in 1975, compared the histology of 30 cases of Löffler's with 32 cases of EMF drawn from Uganda, Nigeria, and Brazil [66]. On the basis of this work, Olsen proposed three stages of Löffler's [67]. In patients with 1 to 2 mo of symptoms prior to autopsy, an eosinophilic myocarditis marked the necrotic stage. Those who died after 10 mo of symptoms had endocardial thickening and thrombosis rather than myocarditis. Among those 16 Löffler patients with more than 2 y of symptoms prior to autopsy, Olsen described a final fibrotic stage that he found identical to EMF. In a clinical and echocardiographic study published in 1983, Davies and colleagues confirmed these findings [31]. In 11 patients from the United Kingdom on the one hand, and 47 patients from India and Brazil on the other, they found no significant differences between fibrotic stage Löffler's and EMF.

Endomyocardial biopsies have failed, however, to demonstrate an eosinophilic myocarditis in EMF. In a series of 49 patients with EMF who underwent biopsies in Uganda, none had tissue eosinophilia despite early presentation in several cases [68]. Attempts to reproduce the Nigerian filariasis findings in other small studies have also failed to show a difference in prevalence of parasite exposure or eosinophilia between EMF cases and controls [69],[70]. In Uganda, one study found that 60% of echocardiographic cases had at least mild eosinophilia compared with 10% of controls (odds ratio 4.6) [30]. Another small study from this country has not shown a difference in rates of eosinophilia [24].

More recently, Andy and colleagues in Nigeria have argued in favor of the helminth-driven eosinophilia hypothesis. In a fascinating study weakened somewhat by lack of diagnostic confirmation, the investigators found an inverse relationship between eosinophil levels and duration of EMF disease [46]. In 89 cases of EMF, only 20% of patients who presented within 6 mo of symptom onset had normal eosinophil concentrations.

Aside from inconsistencies between the pathology of Löffler's and EMF, the mismatch between the geography of EMF and the ubiquity of parasite-induced eosinophilia calls into question the relationship between these entities [71]. Despite the burden of tropical pulmonary eosinophilia on the basis of lymphatic filariasis in Southeast Asia, for example, these countries have not reported much EMF. Rural Haiti has not reported any EMF cases, despite an active echocardiography service at Deschapelles in the Artibonite Valley [72]. Ecological research of disease causation leaves much room for confounding.

Some have sought a more direct connection between EMF and malarial infection. EMF cases in Uganda have disproportionately come from Rwanda-Burundi immigrant families [73]. While the poverty of these migrants confounds association, others have suggested that movement from zones of lower to higher malaria prevalence might hold the key. Following van der Geld, during the late 1960s Shaper and colleagues found increased levels of anti-malarial and anti-heart antibodies among these migrants and EMF cases in particular [74],[75],[76]. Ziegler, Patel, and colleagues identified a series of familial cases of EMF among Rwanda-Burundi migrants who had massive splenomegaly, a condition associated with malaria-induced immune hyper-reactivity [68],[77]. While the prevalence of plasmodial species does not match the geographic distribution of EMF, these findings point to changes in immunity as a possible pathway from malaria to endocardial disease.

In a separate line of inquiry in Kerala State, India, the high prevalence of EMF along a coastal zone free of filariasis has led investigators to pursue a geochemical hypothesis. Valiathan and Kartha have speculated that cerium or thorium present in monazite deposits may explain regional variation in EMF prevalence in this region [23],[78]. No empirical studies have yet come forward to support this theory.

Investigations into nutritional factors in EMF have focused on a possible connection with cassava toxicity. A case-control study from Uganda has shown an association between EMF and markers of poverty such as farming, lack of shoes, and cassava-based diets with little animal protein [30]. Some have suggested that cerium-mediated cassava toxicity in the setting of protein deficiency may play a role in the pathogenesis of EMF [79]. Despite the known role of cyanogens from improperly processed cassava in konzo, an upper-motor neuron disease reported from Central and East Africa, cardiac manifestations have not had a part in these outbreaks [80].

Future Directions

Given the difficulty of cardiovascular research in resource-poor settings, the supply of theories about EMF has exceeded the reach of investigation. The disease accounts for a striking proportion of heart failure in some regions. The dissemination of echocardiography in tropical countries should facilitate prospective studies that clarify case definition and generate new insights into the mechanisms of heart failure in sub-Saharan Africa. At the same time, molecular techniques could bring new life to old ideas.

The fusion protein FIP1L1-PDGFRα, a constitutively activated tyrosine kinase found in as many as half of those with the idiopathic hypereosinophilic syndrome, has emerged as a therapeutic target for imatinib [81]. The prevalence of FIP1L1-PDGFRα among those with EMF could give another important clue about the etiology and treatment of this disease.

Studies that measure levels of markers, such as C-reactive peptide or inflammatory cytokines such as tumor necrosis factor α, could help explore the role of inflammation in EMF and suggest therapeutic strategies in early forms of the disease [82].

Echocardiographic studies of patients with hyper-reactive malarial splenomegaly could shed light on the prevalence of early endocardial disorders in this population.

The recent finding that serotonin acts as a chemotactic factor for eosinophils may reignite inquiries into the role of this pathway in EMF [83]. Zanettini and colleagues have found that some anti-Parkinson medications induce valvular fibrosis via their action on 5HT2B receptors [84]. Could polymorphisms in this receptor influence susceptibility to EMF in the presence of intermittent eosinophilia?

Box 1. Key Learning Points

  • Endomyocardial fibrosis, a restrictive cardiomyopathy, has a high prevalence in tropical regions of sub-Saharan Africa, South Asia, and South America.
  • We found no conclusive evidence that parasite-induced eosinophilia explains the pathogenesis of this condition, but the etiological role of eosinophils remains an open question.
  • Uncertainty continues about the distribution and causes of the disease.

Box 2. Five Key Papers in the Field

  1. Davies JNP (1948) Endomyocardial fibrosis in Uganda. East Afr Med J 25: 10–16.
  2. Parry EH, Abrahams DG (1965) The natural history of endomyocardial fibrosis. Q J Med 34: 383–408.
  3. Connor DH, Somers K, Hutt MS, Manion WC, D'Arbela PG (1967) Endomyocardial fibrosis in Uganda (Davies' disease). 1. An epidemiologic, clinical, and pathologic study. Am Heart J 74: 687–709.
  4. Andy JJ, Ogunowo PO, Akpan NA, Odigwe CO, Ekanem IA, et al. (1998) Helminth associated hypereosinophilia and tropical endomyocardial fibrosis (EMF) in Nigeria. Acta Trop 69: 127–140.
  5. Rutakingirwa M, Ziegler JL, Newton R, Freers J (1999) Poverty and eosinophilia are risk factors for endomyocardial fibrosis (EMF) in Uganda. Trop Med Int Health 4: 229–235.

Supporting Information

Video S1.

Echocardiogram in a 25 year-old man with predominantly right ventricular EMF from eastern Rwanda. Apical four-chamber view. Note the marked dilatation of the right atrium.


(2.01 MB CDR)


We would like to thank Dan Connor, Kris Somers, and three anonymous reviewers for their comments on an earlier version of this paper. We would also like to thank Peter Weller for his advice on eosinophilic disease in the tropics.

Author Contributions

Conceived and designed the experiments: GB JZ EP. Analyzed the data: GB JZ EP. Wrote the paper: GB JZ EP. Initiated this review and wrote the first draft: GB Contributed substantially to the conception and revision of the paper: JZ EP.


  1. 1. Davies JNP (1948) Endomyocardial fibrosis in Uganda. East Afr Med J 25: 10–16.
  2. 2. Ball JD, Williams AW, Davies JN (1954) Endomyocardial fibrosis. Lancet 266: 1049–1054.
  3. 3. Connor DH, Somers K, Hutt MS, Manion WC, D'Arbela PG (1967) Endomyocardial fibrosis in Uganda (Davies' disease). 1. An epidemiologic, clinical, and pathologic study. Am Heart J 74: 687–709.
  4. 4. Williams A (1938) Heart disease in the native population of Uganda. East African Medical Journal 15: 279.
  5. 5. Hutt MS (1983) Epidemiology aspects of endomyocardial fibrosis. Postgrad Med J 59: 142–146.
  6. 6. Lopez AD, Disease Control Priorities Project (2006) Global burden of disease and risk factors. New York: Oxford University Press.
  7. 7. McKenna W, Nordet P, Martin I, Gyarfas I, Thiene G, et al. (1996) Report of the 1995 World Health Organization/International Society and Federation of Cardiology Task Force on the Definition and Classification of Cardiomyopathies. Circulation 93: 841–842.
  8. 8. Freers J, Hakim J, Myanja-Kizza H, Parry E (2004) The heart. In: Parry E, Godfrey R, Mabey D, Gill G, editors. Principles of medicine in Africa. Cambridge: Cambridge University Press. pp. 837–886.
  9. 9. D'Arbela PG, Mutazindwa T, Patel AK, Somers K (1972) Survival after first presentation with endomyocardial fibrosis. Br Heart J 34: 403–407.
  10. 10. Barretto AC, da Luz PL, de Oliveira SA, Stolf NA, Mady C, et al. (1989) Determinants of survival in endomyocardial fibrosis. Circulation 80: I177–182.
  11. 11. Gupta PN, Valiathan MS, Balakrishnan KG, Kartha CC, Ghosh MK (1989) Clinical course of endomyocardial fibrosis. Br Heart J 62: 450–454.
  12. 12. Parry EH, Abrahams DG (1965) The natural history of endomyocardial fibrosis. Q J Med 34: 383–408.
  13. 13. Moraes F, Lapa C, Hazin S, Tenorio E, Gomes C, et al. (1999) Surgery for endomyocardial fibrosis revisited. Eur J Cardiothorac Surg 15: 309–312. discussion 312–303.
  14. 14. Schneider U, Jenni R, Turina J, Turina M, Hess OM (1998) Long-term follow up of patients with endomyocardial fibrosis: effects of surgery. Heart 79: 362–367.
  15. 15. Metras D, Coulibaly AQ, Ouattara K (1987) Recent trends in the surgical treatment of endomyocardial fibrosis. J Cardiovasc Surg (Torino) 28: 607–613.
  16. 16. Cherian SM, Jagannath BR, Nayar S, Cherian KM (2006) Successful reoperation after 17 years in a case of endomyocardial fibrosis. Ann Thorac Surg 82: 1115–1117.
  17. 17. Dubost C, Prigent C, Gerbaux A, Maurice P, Passelecq J, et al. (1983) Surgical approaches in endomyocardial disease. Postgrad Med J 59: 160–161.
  18. 18. Obituaries (1998) Jack Neville Phillip Davies. BMJ 317: 1662.
  19. 19. Corssmit EP, Trip MD, Durrer JD (1999) Loffler's endomyocarditis in the idiopathic hypereosinophilic syndrome. Cardiology 91: 272–276.
  20. 20. Löffler W (1936) Endocarditis parietalis fibroplastica mit Bluteosinophilie. J Suisse Med 66: 817–820.
  21. 21. Falase AO (1985) Are eosinophils the cause of endomyocardial fibrosis in the tropics? Afr J Med Med Sci 14: 1–2.
  22. 22. Shaper AG (1993) What's new in endomyocardial fibrosis? Lancet 342: 255–256.
  23. 23. Valiathan SM, Kartha CC (1990) Endomyocardial fibrosis–the possible connexion with myocardial levels of magnesium and cerium. Int J Cardiol 28: 1–5.
  24. 24. Patel AK, D'Arbela PG, Somers K (1977) Endomyocardial fibrosis and eosinophilia. Br Heart J 39: 238–241.
  25. 25. Williams AW, Ball JD, Davies JN (1954) Endomyocardial fibrosis in Africa: its diagnosis, distribution and nature. Trans R Soc Trop Med Hyg 48: 290–305; discussion, 306–211.
  26. 26. Hassan WM, Fawzy ME, Al Helaly S, Hegazy H, Malik S (2005) Pitfalls in diagnosis and clinical, echocardiographic, and hemodynamic findings in endomyocardial fibrosis: a 25-year experience. Chest 128: 3985–3992.
  27. 27. Bertrand E, Cherian G, Das S, Dubost C, Falase A, et al. (1984) Cardiomyopathies. Technical report series 697. Geneva: World Health Organization.
  28. 28. Acquatella H, Schiller NB, Puigbo JJ, Gomez-Mancebo JR, Suarez C, et al. (1983) Value of two-dimensional echocardiography in endomyocardial disease with and without eosinophilia. A clinical and pathologic study. Circulation 67: 1219–1226.
  29. 29. Bedford DE, Konstam GLS (1946) Heart failure of unknown aetilogy in Africans. Brit Heart J 8: 236.
  30. 30. Rutakingirwa M, Ziegler JL, Newton R, Freers J (1999) Poverty and eosinophilia are risk factors for endomyocardial fibrosis (EMF) in Uganda. Trop Med Int Health 4: 229–235.
  31. 31. Davies J, Spry CJ, Vijayaraghavan G, De Souza JA (1983) A comparison of the clinical and cardiological features of endomyocardial disease in temperate and tropical regions. Postgrad Med J 59: 179–185.
  32. 32. Falase AO (1983) Endomyocardial fibrosis in Africa. Postgrad Med J 59: 170–178.
  33. 33. Ferreira B, Matsika-Claquin MD, Hausse-Mocumbi AO, Sidi D, Paquet C (2002) [Geographic origin of endomyocardial fibrosis treated at the central hospital of Maputo (Mozambique) between 1987 and 1999]. Bull Soc Pathol Exot 95: 276–279.
  34. 34. Makene WJ (1970) Endomyocardial fibrosis in Tanzania (mainland). East Afr Med J 47: 91–96.
  35. 35. Rees P (1969) The occurrence and recognition of endomyocardial fibrosis of the right ventricle in coastal Tanzania. Trans R Soc Trop Med Hyg 63: 650–655.
  36. 36. Nwokolo C (1955) Endomyocardial fibrosis and other obscure cardiopathies in eastern Nigeria. West Afr Med J 4: 103–116.
  37. 37. Ladipo GO, Froude JR, Parry EH (1977) Pattern of heart disease in adults of the Nigerian savanna: a prospective clinical study. Afr J Med Med Sci 6: 185–192.
  38. 38. Abrahams DG (1962) Endomyocardial fibrosis of the right ventricle. Q J Med 31: 1–20.
  39. 39. Abrahams DG (1959) An unusual form of heart-disease in West Africa; its relation to endomyocardial fibrosis. Lancet 2: 111–112.
  40. 40. Yin R (2000) Endomyocardial fibrosis in China. Chin Med Sci J 15: 55–60.
  41. 41. Berensztein CS, Pineiro D, Marcotegui M, Brunoldi R, Blanco MV, et al. (2000) Usefulness of echocardiography and doppler echocardiography in endomyocardial fibrosis. J Am Soc Echocardiogr 13: 385–392.
  42. 42. Freers J, Mayanja-Kizza H, Rutakingirwa M, Gerwing E (1996) Endomyocardial fibrosis: why is there striking ascites with little or no peripheral oedema? Lancet 347: 197.
  43. 43. Vijayaraghavan G, Davies J, Sadanandan S, Spry CJ, Gibson DG, et al. (1983) Echocardiographic features of tropical endomyocardial disease in South India. Br Heart J 50: 450–459.
  44. 44. Maro E, Janabi M (2004) Echocardiographic profile of endomyocardial fibrosis in Tanzania, East Africa. Cent Afr J Med 50: 91–94.
  45. 45. Cockshott WP, Saric S, Ikeme AC (1967) Radiological findings in endomyocardial fibrosis. Circulation 35: 913–922.
  46. 46. Andy JJ, Ogunowo PO, Akpan NA, Odigwe CO, Ekanem IA, et al. (1998) Helminth associated hypereosinophilia and tropical endomyocardial fibrosis (EMF) in Nigeria. Acta Trop 69: 127–140.
  47. 47. Sliwa K, Damasceno A, Mayosi BM (2005) Epidemiology and etiology of cardiomyopathy in Africa. Circulation 112: 3577–3583.
  48. 48. Shaper AG (1967) Plantain diets, serotonin, and endomyocardial fibrosis. Am Heart J 73: 432–434.
  49. 49. McKinney B, Crawford MA (1965) Fibrosis in guinea pig heart produced by plantain diet. Lancet 2: 880–882.
  50. 50. Crawford MA (1963) Endomyocardial fibrosis and carcinoidosis. A common denominator? Am Heart J 66: 273–276.
  51. 51. Crawford MA (1962) Excretion of 5-hydroxyindolylacetic acid in East Africans. Lancet 1: 352–353.
  52. 52. Foy JM, Parrat JR (1962) Urinary excretion of 5-hydroxyindoleacetic acid in West Africans. Lancet 1: 942–943.
  53. 53. McKinney B (1976) Endocardial changes produced in Patus monkeys by the ablation of cardiac lymphatics and the administration of a plantain diet. Am Heart J 91: 484–491.
  54. 54. McKinney B (1975) Studies on the experimental production of endomyocardial fibrosis and cardiomegaly of unknown origin by dietary means. Am Heart J 90: 206–214.
  55. 55. Ojo GO (1970) The pathogenesis of endomyocardial fibrosis: the question of 5-hydroxytryptamine. Br Heart J 32: 671–674.
  56. 56. Edge J (1946) Myocardial fibrosis following arsenical therapy: report of a case. Lancet 248: 675–677.
  57. 57. Gray IR (1951) Endocardial fibrosis. Br Heart J 13: 387–396.
  58. 58. Clark GM, Valentine E, Blount SG Jr (1956) Endocardial fibrosis simulating constrictive pericarditis; report of a case with determinations of pressure in the right side of the heart and eosinophilia. N Engl J Med 254: 349–355.
  59. 59. Giraud G, Latour H, Puech P, Olivier G, Hertault J (1958) Cardiopathie filarienne: etude hemodynamique. Arch Mal Coeur Vaiss 51: 546–557.
  60. 60. Fournier P, Voisin C, Pauchant M, Macquet V (1961) [Parietal fibroplastic endocarditis and filariasis. Clinical, hemodynamic and anatomical study.]. Lille Med 6: 42–47.
  61. 61. Brockington IF, Olsen EG, Goodwin JF (1967) Endomyocardial fibrosis in Europeans resident in tropical Africa. Lancet 1: 583–588.
  62. 62. Ive FA, Willis AJ, Ikeme AC, Brockington IF (1967) Endomyocardial fibrosis and filariasis. Q J Med 36: 495–516.
  63. 63. Ive F, Brockington I (1966) Endomyocardial fibrosis and filariasis. Lancet 69: 212.
  64. 64. Nutman TB, Miller KD, Mulligan M, Ottesen EA (1986) Loa loa infection in temporary residents of endemic regions: recognition of a hyperresponsive syndrome with characteristic clinical manifestations. J Infect Dis 154: 10–18.
  65. 65. Berenguer A, Plancha E, Munoz Gil J (2003) Right ventricular endomyocardial fibrosis and microfilarial infection. Int J Cardiol 87: 287–289.
  66. 66. Brockington IF, Olsen EG (1973) Löffler's endocarditis and Davies' endomyocardial fibrosis. Am Heart J 85: 308–322.
  67. 67. Olsen EG (1983) Pathological aspects of endomyocardial fibrosis. Postgrad Med J 59: 135–141.
  68. 68. Patel AK, Ziegler JL, D'Arbela PG, Somers K (1971) Familial cases of endomyocardial fibrosis in Uganda. Br Med J 4: 331–334.
  69. 69. Carlisle R, Ogunba EO, McFarlane H, Onayemi OA, Oyeleye VO (1972) Immunoglobulins and antibody to Loa loa in Nigerians with endomyocardial fibrosis and other heart diseases. Br Heart J 34: 678–680.
  70. 70. Urhoghide GE, Falase AO (1987) Degranulated eosinophils, eosinophil granule basic proteins and humoral factors in Nigerians with endomyocardial fibrosis. Afr J Med Med Sci 16: 133–139.
  71. 71. Wilson ME, Weller PF (2006) Eosinophilia. In: Guerrant RL, Walker DH, Weller PF, editors. Tropical infectious diseases: principles, pathogens & practice. 2nd edition. Philadelphia: Churchill Livingstone. pp. 1478–1495.
  72. 72. Fett JD, Christie LG, Carraway RD, Murphy JG (2005) Five-year prospective study of the incidence and prognosis of peripartum cardiomyopathy at a single institution. Mayo Clin Proc 80: 1602–1606.
  73. 73. Shaper AG, Coles RM (1965) The Tribal distribution of endomyocardial fibrosis in Uganda. Br Heart J 27: 121–127.
  74. 74. Shaper AG, Kaplan MH, Foster WD, Macintosh DM, Wilks NE (1967) Immunological studies in endomyocardial fibrosis and other forms of heart-disease in the tropics. Lancet 1: 598–600.
  75. 75. Shaper AG, Kaplan MH, Mody NJ, McIntyre PA (1968) Malarial antibodies and autoantibodies to heart and other tissues in the immigrant and indigenous peoples of Uganda. Lancet 1: 1342–1346.
  76. 76. van der Geld H, Peetoom F, Somers K, Kanyerezi BR (1966) Immunohistological and serological studies in endomyocardial fibrosis. Lancet 2: 1210–1213.
  77. 77. Bedu-Addo G, Bates I (2002) Causes of massive tropical splenomegaly in Ghana. Lancet 360: 449–454.
  78. 78. Kutty VR, Abraham S, Kartha CC (1996) Geographical distribution of endomyocardial fibrosis in south Kerala. Int J Epidemiol 25: 1202–1207.
  79. 79. Sezi CL (1996) Effect of protein deficient cassava diet on Cercopithecus aethiops hearts and its possible role in the aetiology and pathogenesis of endomyocardial fibrosis in man. East Afr Med J 73: S11–S16.
  80. 80. Tylleskar T, Banea M, Bikangi N, Cooke RD, Poulter NH, et al. (1992) Cassava cyanogens and konzo, an upper motoneuron disease found in Africa. Lancet 339: 208–211.
  81. 81. Cools J, DeAngelo DJ, Gotlib J, Stover EH, Legare RD, et al. (2003) A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome. N Engl J Med 348: 1201–1214.
  82. 82. Sliwa K, Fett J, Elkayam U (2006) Peripartum cardiomyopathy. Lancet 368: 687–693.
  83. 83. Boehme SA, Lio FM, Sikora L, Pandit TS, Lavrador K, et al. (2004) Cutting edge: serotonin is a chemotactic factor for eosinophils and functions additively with eotaxin. J Immunol 173: 3599–3603.
  84. 84. Zanettini R, Antonini A, Gatto G, Gentile R, Tesei S, et al. (2007) Valvular heart disease and the use of dopamine agonists for Parkinson's disease. N Engl J Med 356: 39–46.
  85. 85. Ijaola O, Falase AO (1990) Distribution of antibodies against Coxsackie B viruses, arboviruses and Toxoplasma gondii among patients with endomyocardial fibrosis (EMF) compared with normal subjects from EMF endemic and non-endemic zones of Nigeria. Afr J Med Med Sci 19: 93–103.
  86. 86. Shaper AG (1966) Endomyocardial fibrosis and rheumatic heart-disease. Lancet 1: 639–641.
  87. 87. Eling WM, Jerusalem CR, Heinen-Borries UJ, Hermsen CC, van Run-van Breda JJ (1988) Is malaria involved in the pathogenesis of tropical endomyocardial fibrosis? Acta Leiden 57: 47–52.
  88. 88. Shaper AG (1972) Cardiovascular disease in the tropics. II. Endomyocardial fibrosis. Br Med J 3: 743–746.
  89. 89. Jaiyesimi F (1982) Controversies and advances in endomyocardial fibrosis: a review. Afr J Med Med Sci 11: 37–46.
  90. 90. Brockington IF, Olsen EG (1972) Eosinophilia and endomyocardial fibrosis. Postgrad Med J 48: 740–741.
  91. 91. Davies H (1990) Endomyocardial fibrosis and the tuberous diet. Int J Cardiol 29: 3–8.
  92. 92. Connor DH, Somers K, Hutt MS, Manion WC, D'Arbela PG (1968) Endomyocardial fibrosis in Uganda (Davies' disease). 2. An epidemiologic, clinical, and pathologic study. Am Heart J 75: 107–124.
  93. 93. Abrahams DG (1962) Endomyocardial fibrosis of the right ventricle. Quart J Med 31: 1–20.
  94. 94. Nkowolo C (1968) Correspondence. Experimental production of endomyocardial fibrosis. Lancet 272: 102.
  95. 95. Bertrand E, Renambot J, Chauvet J, Le Bras M, Lamouche P, et al. (1975) [14 cases of constrictive endocardial fibrosis (or endomyocardial fibrosis]. Arch Mal Coeur Vaiss 68: 625–635.
  96. 96. Amoah AG, Kallen C (2000) Aetiology of heart failure as seen from a National Cardiac Referral Centre in Africa. Cardiology 93: 11–18.
  97. 97. Kimbally-Kaky G, Ekoba J, Nkoua JL, Bouramoue C (2000) [Endomyocardial fibrosis: report of 22 Congolese cases]. Ann Cardiol Angeiol (Paris) 49: 287–295.
  98. 98. Turner PP, Manson-Bahr PE (1960) Endomyocardial fibrosis in Kenya and Tanganyika Africans. Br Heart J 22: 305–310.
  99. 99. Kingue S, Dzudie A, Menanga A, Akono M, Ouankou M, et al. (2005) [A new look at adult chronic heart failure in Africa in the age of the Doppler echocardiography: experience of the medicine department at Yaounde General Hospital]. Ann Cardiol Angeiol (Paris) 54: 276–283.
  100. 100. Maru M (1993) The changing pattern of cardiovascular diseases in Ethiopia. East Afr Med J 70: 772–776.
  101. 101. Sachs JD, Amoako KY, Aninat E, Diabre DCZ, Doryan E, et al. (2001) Macroeconomics and health: investing in health for economic development. Geneva: World Health Organization.
  102. 102. Hodes RM (1988) Pattern of heart disease in Ethiopia as seen in a cardiology referral clinic. Cardiology 75: 458–464.
  103. 103. Harling D, Marsden P, Ridley D (1965) Some observations on the pattern of heart disease in the gambia. Trans R Soc Trop Med Hyg 59: 628–641.
  104. 104. Oyoo GO, Ogola EN (1999) Clinical and socio demographic aspects of congestive heart failure patients at Kenyatta National Hospital, Nairobi. East Afr Med J 76: 23–27.
  105. 105. Diallo B, Sanogo K, Diakite S, Diarra M, Toure M (2004) L'insuffisance cardiaque a l'hopital du point G. Mali Med 19: 15–17.
  106. 106. Thiam M (2002) L'insuffisance cardiaque en milieu cardiologique africain. Bull Soc Pathol Exot 96: 217–218.
  107. 107. Steenekamp JH, Simson IW, Theron W (1992) Cardiovascular causes of death at Tshepong Hospital in 1 year, 1989–1990. A necropsy study. S Afr Med J 81: 142–146.
  108. 108. Richter J, Dengler A, Mohammed EG, Ali GM, Abdel-Rahim I, et al. (1990) Results of echocardiographic examinations in a regional hospital of central Sudan. Trans R Soc Trop Med Hyg 84: 749–752.
  109. 109. Guimaraes A (1993) Natural history and current status in Brazil. In: Valiathan M, Somers K, Kartha CC, editors. Endomyocardial fibrosis. Delhi: Oxford University Press. pp. 37–54.
  110. 110. Suarez J, Suarez C (1973) Fibrosis endomiocardica: estudio morfologico de 5 casos. Arch Inst Cardiol Mex 43: 58–67.
  111. 111. Datta BN, Babu SK, Khattri HN, Bidwai PS, Wahi PL (1977) Endomyocardial fibrosis in Chandigarh area, India. A study of nine autopsies. Trop Geogr Med 29: 346–352.
  112. 112. Rashwan MA, Ayman M, Ashour S, Hassanin MM, Zeina AA (1995) Endomyocardial fibrosis in Egypt: an illustrated review. Br Heart J 73: 284–289.