|Year : 2015 | Volume
| Issue : 1 | Page : 45-50
Endomyocardial fibrosis: Seven decades later in the Nigerian setting
Godsent Chichebem Isiguzo1, Onyebuchi Micheal2, James Audu Onuh3, Adesua Sandra Muoneme3, Nandom Kenneth Bitrus3, Basil Nwaneri Okeahialam3
1 Department of Internal Medicine, Federal Teaching Hospital Abakaliki, Ebonyi, Nigeria
2 Consultant Physician/Lecturer, College of Medicine, University of Nigeria, Enugu Campus, Enugu, Nigeria
3 Department of Internal Medicine, Jos University Teaching Hospital, Jos, Plateau, Nigeria
|Date of Web Publication||5-Jan-2015|
Godsent Chichebem Isiguzo
Department of Internal Medicine, Federal Teaching Hospital, P.M.B 102 Abakaliki, Ebonyi
Source of Support: None, Conflict of Interest: None
Background: Endomyocardial fibrosis (EMF), an obliterative cardiomyopathy of uncertain etiology, is the most common restrictive cardiomyopathy worldwide with no specific treatment and usually associated with poor prognosis due to late presentation. First described in the literature in 1946 among Africans, the prevalence seem to be decreasing, but without much change in its management in the region due to late presentation and inadequate surgical responsiveness. Earlier literature described EMF as a disease of the rain forest, only restricted to dwellers in the coastal regions. Despite the growing body of knowledge on this condition, there is not enough corresponding advancement in therapeutic interventions for the sufferers in Nigeria.
Materials and Methods: Between May 2010 and July 2011, we reviewed cases of endomyocardial fibrosis presenting to the cardiology unit of Jos University Teaching Hospital, Plateau State Nigeria. The institutional board of the hospital approved the review, and consent was obtained from the patients/guardians. Effort was made to withhold identity of the patients in accordance with established protocol.
Result: The first case was an 18-year-old female student with features of chronic heart failure who has earlier been misdiagnosed as having rheumatic valvular heart disease, but had biventricular EMF. Case 2 was a 33-year-old man who presented with breathlessness and hemoptysis and was erroneously on treatment for tuberculosis. Echocardiography revealed right ventricular EMF. The final case was a 27-year-old farmer with cough, progressive shortness of breath and abdominal swelling. Holter monitoring revealed ventricular and atrial arrhythmias, and echocardiography showed pericardial effusion with features of right ventricular EMF. He had bouts of arrhythmia with collapse, and finally died suddenly.
Conclusion: There have been little advances in management of EMF seven decades after it was discovered, and despite being one of the major causes of heart failure in the tropics, awareness and response to management in these areas have lagged behind.
Keywords: Cardiomyopathy, endomyocardial fibrosis, heart failure, nigeria
|How to cite this article:|
Isiguzo GC, Micheal O, Onuh JA, Muoneme AS, Bitrus NK, Okeahialam BN. Endomyocardial fibrosis: Seven decades later in the Nigerian setting. Nig J Cardiol 2015;12:45-50
|How to cite this URL:|
Isiguzo GC, Micheal O, Onuh JA, Muoneme AS, Bitrus NK, Okeahialam BN. Endomyocardial fibrosis: Seven decades later in the Nigerian setting. Nig J Cardiol [serial online] 2015 [cited 2021 Jun 17];12:45-50. Available from: https://www.nigjcardiol.org/text.asp?2015/12/1/45/148488
| Introduction|| |
Endomyocardial fibrosis (EMF) was first described by Bedford and Konstam in 1946 among soldiers of West African origin during the 2 nd World war  and in 1948 by pathologist Jack Davies in Kampala, Uganda.  It is a form of restrictive cardiomyopathy in which there is fibrotic thickening and obliteration of the right ventricle (RVEMF), left ventricle (LVEMF) or both (BVEMF). There is a predilection for ventricular apices and inflow regions, sparing outflow tracts; with restriction of ventricular diastole and destruction of papillary muscles of the atrio-ventricular valves. When fibrotic processes involve the papillary muscles and the sub-valvular mechanism, valve immobility results in AV valve incompetence. The fibrotic process does not involve the valve leaflets, the atria or the great vessels.
EMF though worldwide in occurrence, is mainly seen in tropical and subtropical regions, relatively uncommon in Northern and Southern Africa.  It has been reported in Nigeria, Uganda, Kenya, Tanzania, Mozambique, Gabon, Congo, Cameroon, Sudan, Cote d'Ivoire, Ghana, Brazil and India. ,,, All these regions are within the tropical belt, 15 0 of the equator. Endomyocardial fibrosis attracted a large volume of literature in the 70s and 80s, but has lately been classified under the neglected diseases, and works on it mostly describe clinical series of patients in advanced stages of the disease, with large-scale epidemiologic studies lacking.  There is therefore need for expansion of echocardiographic referral centers and the development of a sub-Saharan Africa heart failure registry so as to clarify the epidemiology of EMF in this region.  In Uganda, it is the most common cause of heart disease in hospitalized patients, accounting for 20% of cases referred for echocardiography,  while in the only epidemiological data in the continent, a community survey in Mozambique involving 1249 patients, there were 211 cases (19.8%) out of which 33 had surgery. 
Initial report from Nigeria was of the opinion that it occurs in hot and humid coastal areas.  Most of the cases seen at Ibadan, Nigeria were natives of South-western and South-eastern regions, with no patient reported in heart failure admissions from Hausa and Fulani tribes who usually reside in the northern region of the country. 
The etio-pathogenesis of EMF remains much of an enigma, with several unvalidated hypothesis, ranging from chronic beriberi, loa-loa infection, toxoplasma gondii infection, filariasis induced occlusion of cardiac lymphatics, anemia, helminthic infection, schistosomiasis, hypersensitivity reaction to streptococcal infection and rheumatic heart disease continuum. ,,,,, As has been seen in carcinoid heart disease, which produces endocardial thickening with high levels of serotonin, the possibility of excessive consumption of plantains with high serotonin content causing EMF was also postulated.  The debate on it being part of Loffler's hypereosinophilia syndrome still rages decades later.
Peak age of presentation was initially placed between 10 and 19 years, but more recent reports give average age of 33 years.  In Uganda there is a bimodal peak of 10 years and 30 years.  Earlier reports gave female sex preponderance with ratio of 2:1.  Ibadan series showed no sex dominance, while others reported 2:1 in favour of males.  Patients are rarely seen in the acute phase, rather they present in late stages at which time outcome is poor. Features seen are of bi-ventricular EMF, right ventricular EMF or left ventricular EMF in that order. 
We present three cases of EMF in individuals with average age of 28 years, seen in a space of one year (May 2010 to July 2011) in Northern Nigeria. The patients/relatives gave consent for us to report these cases, and the Jos University teaching hospital institutional review board approved the study. They bring to fore, the unfortunate realization that more than seven decades later and despite the increased body of knowledge and the speculated role of autoimmunity/search for immunosuppressive therapy,  no effective therapy still exist and mean survival of 2 years after diagnosis has not changed much.
| Results|| |
BJ, an 18-year-old student [Figure 1] was referred to Jos University Teaching Hospital (JUTH) on account of 3-year history of heart failure. She had dropped out of school 3 years earlier due to ill-health.
She had four hospital admissions since the onset of her condition, initially as a case of congestive cardiac failure from rheumatic valvular heart disease. The unsatisfactory response to treatment led to her referral.
Physical examination was remarkable for 'egg on stick appearance', central cyanosis, generalized hyper pigmentation, breast atrophy, parotid fullness, and bilateral pitting leg edema.
ECG showed sinus rhythm, right axis deviation, left atrial enlargement, left ventricular hypertrophy (LVH) abnormal repolarization abnormalities in the inferior leads [Figure 2].
|Figure 2: Electrocardiograph of case 1 showing sinus rhythm, right axis deviation, left atrial enlargement, left ventricular hypertrophy abnormal repolarization abnormalities in the inferior leads|
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Echocardiography showed dilated right atrium (RA), left atrium (LA) restricted right ventricle (RV) and left ventricle (LV) with apical plaque in the RV, and posterior tethering of the posterior mitral valve leaflet (PMVL). There was severe tricuspid regurgitation (TR), mitral regurgitation (MR), moderate pulmonary regurgitation (PR) and mild pericardial effusion.
Diagnosis was congestive cardiac failure secondary to biventricular EMF.
She was placed on diuretics, digoxin and parenteral antibiotics. She had four sessions of abdominal paracentesis to relieve distension. Twenty-eight days after admission, she developed hypovolemic shock following paracentesis and subsequently passed on despite attempts at resuscitation.
ODB, a 33-year-old man admitted via the accident and emergency unit with 6 months complaint of cough, and 2 months complaint of body swelling. Cough was productive of copious non-foul-smelling sputum, occasionally blood stained, associated with breathlessness, intermittent low grade fever, anorexia and progressive weight loss. He had a history of significant alcohol use and smoking.
On examination, he was chronically ill looking, had bilateral pitting leg edema and Grade 3 finger clubbing.
The pulse rate was 108 beats/minute, small volume and regular, BP was 90/70 mmHg, Jugular venous pressure (JVP) was elevated with engorged neck veins, Apex beat was at the 5 th left intercoastal space mid clavicular line (5LICS MCL). There was right ventricular heave, with normal 1 st and 2 nd heart sounds, right sided S3, loud P2, TR murmur 3/6 loudest at the left parasternal area.
He was tachypnoeic and had features of consolidation on the right mid and left lower zones, had hepato-splenomegally and mild ascites.
The initial working diagnosis was disseminated tuberculosis (pulmonary, myocardial and pericardial) with congestive cardiac failure from myocarditis.
Chest X-ray revealed cardiomegally with full pulmonary conus and oligeamic lung field, and bilateral hilar lymphadenopathy.
He was placed on intravenous frusemide, tablets spironolactone, aspirin and anti- tuberculosis therapy.
By the 3 rd day, patient developed profuse hemoptysis, expectorating more than 200 mls per episode.
ECG showed Low voltage complexes in the limb leads, RAD, RAE, and RVH.
Echocardiography showed endocardial band pulling on the tricuspid valve (Posterior cusp). There were also fibrous bands (plaque) on the apex of the RV, obliterating the cavity. The RA was grossly enlarged (>50 mm). There was thickening of the IVS and LVPW, with reduced LV cavity, and LA, mild to moderate pericardial effusion [Figure 3].
|Figure 3: 2D echocardiogram of case 2 showing endocardial band pulling on the tricuspid valve (Posterior cusp). There were also fibrous bands (plaque) on the apex of the RV, obliterating the cavity. The RA was grossly enlarged (>50 mm). There was thickening of the IVS and LVPW, with reduced LV cavity, and LA, mild to moderate pericardial effusion|
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A diagnosis of right ventricular EMF (RVEMF) with features of pulmonary hypertension and right heart failure was made.
Anti TB drugs and digoxin were stopped. Intravenous frusemide was increased to 100 mg daily, and tablets Carvedolol 3.125 mg daily added.
By the 14 th day, hemoptysis worsened, three units of blood were transfused. Vitamin K and Sildenafil 50mg daily were started and hemoptysis subsided. Patient had another bout of hemoptysis, rapidly deteriorated and died on the 26 th day.
TJ, a 27-year-old male farmer presented with 1-year history of abdominal swelling, progressive breathlessness, palpitation and cough productive of whitish frothy sputum. There was associated PND, no history of facial or leg swelling. He was not known to be hypertensive, and had no known family history of hypertension. He had history of significant alcohol use for more than 3 years.
Physical examination was remarkable for features of biventricular heart failure.
Chest X-ray showed cardiomegally of right ventricular dominance, there were features of pulmonary edema. His INR was mildly prolonged (1.62), while LFT showed mild hypoalbuminemia, conjugated hyperbilirubinemia and elevated liver enzymes (ALP = 337IU/L, ALT = 74IU/L and AST = 144IU/L). Electrolytes, urea, creatinine, complete blood count and ESR were all normal.
ECG revealed RAD, RAE, RVH. Twenty-four hour Holter monitoring revealed 11 atrial ectopics, with 2 couplets and 2 bigeminy. There were 595 ventricular ectopics, containing 383 isolated events, 12 trigeminy, 20 bigeminy, 52 couplets, 10 triplets. He had 2 ST depression events with a depth of 4 mm upsloping, 348 PR variability [Figure 4].
|Figure 4: Summary of 24 hour Holter monitoring of the 3rd case, showing 11 atrial ectopics, with 2 couplets and 2 bigeminy. There were 595 ventricular ectopics, containing 383 isolated events, 12 trigeminy, 20 bigeminy, 52 couplets, 10 triplets. He had 2 ST depression events with a depth of 4 mm upsloping, 348 PR variability|
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Echocardiography showed good systolic function, dilated RA and RV. There was apical plaque in the right ventricle, and endomyocardial fibrous strand restricting both leaflets of the tricuspid, with a moderate to severe tricuspid regurgitation. There was also spontaneous echo contrast in RA, with evidence of pulmonary hypertension and moderate pericardial effusion [Figure 5].
|Figure 5: 2D Echocardiography of the 3rd case, showing good systolic function, dilated RA, RV, There was apical plaque in the right ventricle, and endomyocardial fibrous strand restricting both leaflets of the tricuspid, with a moderate to severe tricuspid regurgitation. There was also spontaneous echo contrast in RA, with evidence of pulmonary hypertension and moderate pericardial effusion|
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Based on the above findings, a diagnosis of Right Ventricular EMF was made, he was subsequently referred to cardiology unit 16 days after admission. Digoxin was stopped and he was started on Sildenafil 25 mg daily, with diuretics.
On the 10 th day on admission, he collapsed in the bathroom, with no loss of consciousness and vital signs were found to be normal.
On the 20 th day on admission, patient was said to have suddenly started gasping after his morning medications, and despite resuscitation, he stopped breathing and was certified dead. The unit requested autopsy, but his family declined.
| Discussion|| |
These three cases were seen within 1 year, they all presented late, a familiar scenario in medical practice in our country, where patients usually come to the hospital after trying other forms of treatment. These cases were seen in the northern part of Nigeria, an area where cases of EMF were thought absent by earlier reports, though two workers have previously documented cases. ,, The low prevalence in the region could have been hinged on low index of clinical suspicion as typified in the reported cases above. Another reason could be due to increased access to medical care and increased availability of echocardiogram in some part of the continent, leading to recognition of diseases in areas in which the disease had not previously been reported, and thus giving insight into the natural history.  The prevalence of EMF showed a decrease in a hospital audit in Enugu in southern Nigeria from country prevalence of 10% to 0.8% in 2002, and the authors questioned if this was a true reflection or from missed diagnosis. 
In two of the cases presented, there was RVEMF while one had BVEMF. The outcome as seen in the above cases was not good and has not improved seven decades after EMF was first noticed.
Clinical features depend on stage of disease and anatomical involvement of the heart. Thirty to 50% of children and adolescents report an initial illness with fever, chills and night sweat with facial swelling, and urticaria.  Most of these features were seen in the patients presented. The illness may disappear or it may lead to rapidly developing cardiac failure and early death or it may evolve into established and apparently inactive EMF with predominantly right ventricular or left ventricular disease. Ascites as seen in case 1 with little or no peripheral edema, otherwise described as "egg-on-stick appearance", is the characteristic clinical feature irrespective of the involved pericardium and unlike congestive cardiac failure the fluid is exudative in 75% of cases with associated peritoneal fibrosis. As seen in the second case, pericardial effusion of variable degree is common. On the whole, clinical presentation varies based on extent of involvement of the ventricles. Isolated RVEMF, with obliterative changes and no tricuspid incompetence, is mildly symptomatic. In this case, the only abnormal clinical finding may be a giant or prominent 'a' wave in the jugular venous pulse. At the other extreme, patients with isolated RVEMF with severe tricuspid regurgitation (TR) present with features of chronic right heart failure with markedly elevated JVP and expansile large 'v' waves, pulsatile liver, hepatomegally, ascites, edema, cyanosis, cachexia and malnutrition. These features were evident in the second case. They may also have pericardial effusion, marked cardiomegally, RV third heart sound, and inconspicuous systolic murmur of TR. The severity of TR rather than the presence of RV diastolic dysfunction is the more important determining factor for the clinical outcome of patients with RVEMF. An occasional patient with severe RVEMF can have cyanosis due to right-to-left atrial shunting through a patent and stretched fossa ovalis defect. Isolated LVEMF, in the absence of AV valve incompetence, is often minimally symptomatic. Hemodynamic study may reveal a prominent 'a' wave in the PA wedge pressure, and LV end diastolic pressure may be elevated. Few patients may present with severe pulmonary venous and pulmonary arterial hypertension entirely due to LV diastolic compliance failure, in the absence of mitral incompetence, but this is distinctly rare.  Features of pulmonary arterial hypertension will depend on the presence of pulmonary venous hypertension resulting from mitral incompetence as well as diastolic LV dysfunction. The second case had clinical evidence of pulmonary hypertension. Biventricular involvement is seen in at least 50% of patients and clinical presentation depends upon the severity of mitral incompetence, tricuspid incompetence and diastolic dysfunction due to obliterative changes in both the ventricles. These patients are hemodynamically more compromised and deteriorate rapidly, and have a poor prognosis. Patients may present with atrial arrhythmias, more commonly atrial fibrillation (AF), or embolic stroke. The third case had several episodes of atrial and ventricular ectopics on 24 hour Holter monitoring, and had an initial history of sudden collapse before his sudden death. It is quite possible that his death could have been from the electrical disturbance. Atrial thrombus, commonly seen in the right atrium, is due to stagnating blood in the large right atrium, especially in the presence of AF. Pericardial effusion is seen in a significant number of patients with RVEMF, and correlates with the severity of the systemic venous congestion. However, it generally does not result in cardiac tamponade and rarely requires pericardiocentesis. Not uncommonly EMF is detected incidentally in patients with rheumatic or other heart diseases.  The first case was initially managed as rheumatic heart disease before referral to the cardiology unit.
Medical treatment options are decongestive therapy, anti-arrhythmic treatment for AF, diuretics for heart failure and oral anticoagulation for AF and pulmonary or systemic embolism. In the article from India,  90% of the patients were receiving digoxin and diuretics on follow-up, a handful of patients with RVEMF had repeated hospitalizations for abdominal paracentesis, to relieve tense ascites (this was done repeatedly in case 1). Pericardiocentesis for cardiac tamponade or large effusion was seldom needed, despite large pericardial effusions being common in severe RVEMF. 
In 1971, Dubost  had introduced surgical treatment of EMF by Endocardial decortications and AV valve replacement. A plane of cleavage can be easily developed and all of the yellow-white thickened endocardium removed. Surgical options are LV endocardiectomy, AV valve repair or replacement and exclusion of fibrotic RV in a pure RVEMF by a bidirectional Glenn (BDG) connection.  In the Mozambique community survey earlier referred to, following meticulous case selection, 33/211 (16%) had prompt surgery with 4/33 (12%) mortality. Procedures employed were endocardial resection (28), valves repair (33), atrial reduction (5), Glen procedure (3), and the most prominent complication was pericardial effusion needing surgery.  Concluding, the learning point from the experience were the need to unveil disease mechanism by model development, exploration of therapeutic targets like anti-inflammatory drugs and modulators, developing new therapeutic approaches, and identification of prognostic factors.
| Conclusions|| |
EMF has remained an enigma seven decades later; the slow advancement of interest in the last 20 years which has led to its classification as a neglected disease, has also been responsible for the seeming decreased prevalence. It is also sad that despite advances in medical knowledge all over the world, majority of health systems in most African nations are yet to evolve adequate capacity for prompt intervention in this prominent cause of cardiovascular morbidity. This case series brings to fore this familiar story of stagnation in our health care delivery and it is hoped that it will serve as a wakeup call to cardiology and cardiovascular surgery practice in sub-Saharan Africa.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]