Endomyocardial Fibrosis: Still a Mystery after 60 Years

Division of Social Medicine and Health Inequalities, Brigham and Women's Hospital, Boston, Massachusetts, USA.
PLoS Neglected Tropical Diseases (Impact Factor: 4.45). 02/2008; 2(2):e97. DOI: 10.1371/journal.pntd.0000097
Source: PubMed


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.

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Available from: Gene Bukhman, Dec 11, 2014
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    • "Clinical research should be coupled with investigations into the biologic basis for various forms of HF. For example, increasing access to echocardiography and early diagnosis may foster a better understanding of EMF while exploration of molecular mechanisms may uncover therapeutic targets [171]. Lastly, where the causes and treatments for some conditions are well known (e.g., RHD, hypertensive heart disease), these conditions still contribute to significant morbidity and mortality on the continent. "
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    ABSTRACT: The heart failure syndrome has been recognized as a significant contributor to cardiovascular disease burden in sub-Saharan African for many decades. Seminal knowledge regarding heart failure in the region came from case reports and case series of the early 20th century which identified infectious, nutritional and idiopathic causes as the most common. With increasing urbanization, changes in lifestyle habits, and ageing of the population, the spectrum of causes of HF has also expanded resulting in a significant burden of both communicable and non-communicable etiologies. Heart failure is sub-Saharan Africa is notable for the range of etiologies that concurrently exist as well as the healthcare environment marked by limited resources, weak national healthcare systems and a paucity of national level data on disease trends. With the recent publication of the first and largest multinational prospective registry of acute heart failure in sub-Saharan Africa, it is timely to review the state of knowledge to date and describe the myriad forms of heart failure in the region. This review discusses several forms of heart failure that are common in sub-Saharan Africa [e.g., rheumatic heart disease, hypertensive heart disease, pericardial disease, various dilated cardiomyopathies, HIV cardiomyopathy, hypertrophic cardiomyopathy, endomyocardial fibrosis, ischemic heart disease, cor pulmonale] and presents each form with regard to epidemiology, natural history, clinical characteristics, diagnostic considerations and therapies. Areas and approaches to fill the remaining gaps in knowledge are also offered herein highlighting the need for research that is driven by regional disease burden and needs.
    Current Cardiology Reviews 04/2013; 9(2). DOI:10.2174/1573403X11309020008
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    • "Historically, one of the most intriguing aspects of the disease is its peculiar occurrence in certain pockets of the world4. The disease is most common in the tropics 15° on either side of the equator5. Isolated case reports have been published from various parts of the world but many of these patients had long stay in the regions of endemicity. "
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    ABSTRACT: Tropical endomyocardial fibrosis in India was a common medical problem in the coastal districts of south India, especially the Kerala State. The clinical and autopsy studies have shown left and right ventricular apical fibrosis, with varying degree of atrioventricular valve regurgitation. Left ventricular endomyocardial fibrosis presents with severe pulmonary hypertension and right ventricular endomyocardial fibrosis presents very high systemic venous pressure and congestive cardiac failure. Surgical management improved the natural history of the disease to some extent. Various infectious and toxic factors were postulated regarding its aetiology. During the last few years, incidence of the disease has decreased considerably. The only explanation identified is the significant improvement in the living standards of the people with the corresponding decline in the childhood malnutrition, infections, worm infestation and associated eosinophilia.
    The Indian Journal of Medical Research 11/2012; 136(5):729-38. · 1.40 Impact Factor
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    • "Our findings offer the first ever evidence to support the postulate that cross reactivity of antibodies against C-terminal sequences of ribosomal P proteins from several animals, plant and protozoal with heart tissue may mediate EMF in a similar manner as C- termini of T. cruzi do for Chaga's disease. Overall, despite previous studies implicating several factors in the etiology of EMF[5], including the evidenced role of ethnicity [6] and suspicions around Infections (Toxoplasmosis, Rheumatic fever, Malaria, Myocarditis and Helminthes [7]), allergy (Autoimmunity and Eosinophilia [8]), malnutrition (Protein or Magnesium deficiency[5], [7]) and toxic agents(Cassava, other plant toxins, Arsenic[9], Cerium, Thorium, Serotonin, or Vitamin D[5]) as the primary EMF insult; none is yet proven[5], [10]. Collectively, the pathology seen in EMF has been suspected to be mediated via similar molecular mimicry mechanisms as is seen in Loffler's and Chaga's disease [16]. "
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    ABSTRACT: Endomyocardial Fibrosis (EMF) -is a chronic inflammatory disease of the heart with related pathology to that of late stage Chaga's disease. Indeed, both diseases are thought to result from auto-immune responses against myocardial tissue. As is the case that molecular mimicry between the acidic termini of Trypanosoma cruzi ribosomal P0, P1 and P2beta (or simply TcP0, TcP1, and TcP2beta) proteins and myocardial tissue causes Chaga's disease, excessive exposure to certain infections, toxins including cassava ones, allergy and malnutrition has been suggested as the possible cause for EMF. Recent studies have defined the proteomic characteristics of the T. cruzi ribosomal P protein-C-termini involved in mediating auto-immunity against Beta1-adrenergic receptors of the heart in Chaga's disease. This study aimed to investigate the similarity of C-termini of TcP0/TcP2beta to sequences and molecules of several plants, microbial, viral and chemical elements- most prior thought to be possible causative agents for EMF. Comparative Sequence alignments and phylogeny using the BLAST-P tool at the Swiss Institute of Biotechnology (SIB) revealed homologs of C-termini of TcP0 and TcP2beta among related proteins from several eukaryotes including the animals (Homo sapiens, C. elegans, D. melanogaster), plants (Arabidopsis thaliana, Zea mays, Glycina Max, Oryza sativa, Rhizopus oryzae) and protozoa (P. falciparum, T. gondii, Leishmania spp).The chemical formulae of the two T.cruzi ribosomal protein C-terminal peptides were found to be C(61)H(83)N(13)O(26)S(1)and C(64)H(87)N(13)O(28)S(1) respectively by Protparam. Both peptides are heavily negatively charged. Constitutively, both auto-antigens predominantly contain Asparagine (D), Glycine (G) and Phenylamine (F), with a balanced Leucine (L) and Methionine (M) percent composition of 7.7%. The afore going composition, found to be non-homologous to all molecules of chemical species in the databases searched, suggests the possible role of a metabolic pathway in the pathogenesis of EMF if aligned with our "molecular mimicry" hypothesis. Our findings provide a "window" to suggest that cross reactivity of antibodies against C-terminal sequences of several animal, plant and protozoal ribosomal P proteins with heart tissue may mediate EMF in a similar manner as C- termini of T. cruzi do for Chaga's disease.
    PLoS ONE 10/2009; 4(10):e7420. DOI:10.1371/journal.pone.0007420 · 3.23 Impact Factor
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