(Chest. 2005;128:3985-3992.)
© 2005
American College of Chest Physicians
Pitfalls in Diagnosis and Clinical, Echocardiographic, and Hemodynamic Findings in Endomyocardial Fibrosis*
A 25-Year Experience
Walid M. Hassan, MD, FCCP;
Mohamed E. Fawzy, MD;
Sumaya Al Helaly, MD;
Hesham Hegazy, MD and
Shahid Malik, MD
* From King Faisal Heart Institute, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Correspondence to: Walid Hassan, MD, FCCP, Consultant and Deputy Head, Cardiology Section, King Faisal Heart Institute (MBC 16), King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh 11211, Saudi Arabia; e-mail: hassanw{at}kfshrc.edu.sa
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Abstract
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Endomyocardial fibrosis (EMF) is a fascinating disease entity of unknown etiology. It is prevalent in the tropical zone. Its essential features are the formation of fibrous tissue on the endocardium and to a lesser extent in the myocardium of the inflow tract and apex of one or both ventricles. It results in endocardial rigidity, atrioventricular valve incompetence secondary to papillary muscle involvement, and progressive reduction of the cavity of the involved ventricle leading to restriction in filling and atrial enlargement. This article will present 21 patients with EMF who were initially referred to our hospital from 1979 to 2004 with different diagnoses: rheumatic heart disease with mitral and or tricuspid regurgitation (n = 9), constrictive pericarditis (n = 6), restrictive cardiomyopathy (n = 1), hypertrophic cardiomyopathy apical type (n = 2), dilated cardiomyopathy (n = 2), and Ebstein malfunction of the tricuspid valve (n = 1). The clinical, echocardiographic, hemodynamic, and angiographic findings in these 21 patients are presented; echocardiographic findings lead to the right diagnosis. The presence of a small ventricle with obliteration of the apex and large atrium shown on two-dimensional echocardiography is highly suggestive of EMF.
Key Words: diagnosis • endomyocardial fibrosis • pitfalls
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Introduction
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Endomyocardial fibrosis (EMF) is a disease entity of unknown etiology that was first described by Davies1 and Conner et al23 in Uganda in 1960. Its essential features are the formation of fibrous tissue on the endocardium and to a lesser extent in the myocardium of the inflow tract and apex of one or both ventricles. It results in endocardial rigidity, atrioventricular valve incompetence secondary to papillary muscle involvement, and progressive reduction of the cavity of the involved ventricle leading to restriction in filling and atrial enlargement.4 The cause of the disease is not known; possibly, abnormal eosinophils are involved in the pathogenesis,567 as eosinophilia is found in some cases of EMF, and similar endocardial fibrotic changes develop in patients with eosinophilic leukemia and Löffler disease.68
Since our first description of the disease in the Middle East in 1980,49 21 more patients have been referred to our hospital over the last 25 years with varying diagnoses. The purpose of this study is to draw the attention of the medical community to the fact that EMF does occur outside the tropical zone and to shed light on the method of reaching the right diagnosis, in particular the echocardiographic findings in this disease.
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Materials and Methods
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Patients
From September 1979 to February 2004, 21 patients (14 men and 7 women; mean age, 33 years; range, 18 to 60 years) were referred to our center for further management with different diagnoses: rheumatic heart disease (RHD) with mitral regurgitation (MR) and/or tricuspid regurgitation (TR) [n = 9], constrictive pericarditis (CP) [n = 6], restrictive cardiomyopathy (RCM) [n = 1], hypertrophic cardiomyopathy (HCM) apical type (n = 2), dilated cardiomyopathy (DCM) [n = 2], and Ebstein malfunction of the tricuspid valve (n = 1). We challenged the referring diagnosis; after the appropriate diagnostic studies, all 21 patients were proven to have EMF: right-sided EMF (n = 7), left-sided EMF (n = 4), and biventricular EMF (n = 10).
Diagnostic Studies
History, physical examination, and routine laboratory data including total and differential WBC, ECG, and chest radiography (CXR) were carried out. Echocardiography was performed in all patients; M-mode and two-dimensional echocardiography were carried out using commercially available machines. Multiple views from several acoustic windows were obtained using the standard technique. In all patients, right and left cardiac catheterization and right and left angiocardiography using biplane cine and coronary angiography were performed. Right ventricular endomyocardial biopsy was performed in nine patients using a Cordis biotome via the right jugular or femoral vein percutaneously.
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Results
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Symptoms and Physical Signs
Onset of symptoms was from 1 to 10 years before admission to the hospital and mainly of diastolic impairment (Table 1
). Three patients were in New York Heart Association (NYHA) functional class II, 13 patients were in NYHA functional class III, and 5 patients were in NYHA functional class IV. Ascites and peripheral edema were noted in patients with right and biventricular EMF.
Laboratory Findings
Eight patients (cases 2, 6, 7, 12, 16, 18, 19, and 21) manifested absolute eosinophilia with counts from 600 to 2,900/µL. Two patients had hypereosinophilic syndrome (cases 16 and 21). Other findings were nonspecific.
ECG
The findings were nonspecific. Eight patients had atrial fibrillation, and all had a slow ventricular rate. One patient had complete heart block (case 17). One patient had bifasicular block (case 3). QS pattern in leads V1 to V4 was present in two patients (cases 12 and 13). The patients with sinus rhythm showed left and/or right atrial enlargement.
CXR
CXR findings were nonspecific. Cardiomegaly was present at varying degrees from mild to severe. There was right atrial enlargement in the patients with right-sided involvement, left atrial enlargement in patients with left-sided involvement, and biatrial enlargement in those with biventricular involvement. Pulmonary venous congestion was seen in patients with left-sided involvement. Myocardial calcification was observed in two patients (cases 13 and 15).
Echocardiography
The left atrium was dilated in left-sided and biventricular EMF, and the right atrium was dilated in right-sided and biventricular EMF. Two-dimensional echocardiography showed the characteristic findings of apical obliteration of the involved ventricle and gross enlargement of the corresponding atrium (Fig 1
) that was best demonstrated in the apical four-chamber view in all patients. Pericardial effusion was noted in six patients with severe congestive heart failure.
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Figure 1.. Bidimensional echocardiographic apical two-chamber view of a patient with left-sided EMF (top, a) and a four-chamber view of a patient with right-sided EMF (bottom, b). RV = right ventricular; LV = left ventricle; RA = right atrium; LA = left atrium.
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Hemodynamic Findings
In patients with right ventricular EMF, right atrial pressure was increased with prominent A waves, which was also seen in the right ventricular and pulmonary artery pressure tracings (Table 2
). The right ventricular pressure tracing showed a dip and high end-diastolic pressure 5 mm Hg higher than the pulmonary diastolic pressure, and the contour of the right ventricular pressure tracing was distorted (Fig 2
). In patients with left-sided involvement, left ventricular end-diastolic pressure was very high. A dip and plateau pattern of the ventricular pressure curve was present in almost all patients. Pulmonary hypertension was present in all patients with left and biventricular EMF (Fig 3
). Left ventricular end-diastolic volume was normal in 12 of 14 patients with left-sided involvement, even in the presence of severe MR. Cardiac index was low in all patients.
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Figure 2.. Right-heart pressure tracing in a patient with right-sided EMF showing increased right atrial pressure with a prominent A wave that is seen also in the right ventricular and pulmonary artery (PA) tracings. The right ventricular pressure tracing has a dip and high end-diastolic pressure that is 5 mm Hg higher than the pulmonary artery diastolic pressure. The pulmonary capillary wedge pressure (PCP) is normal. See Figure 1 legend for expansion of abbreviations.
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Figure 3.. Right and left heart pressure tracing in a patient with biventricular EMF showing elevated RA, RV, pulmonary artery (PA), left ventricular end-diastolic pressure, and pulmonary capillary (P) wedge pressures. A dip and plateau pattern of the ventricular pressure curve is present. See Figure 1 legend for expansion of abbreviations.
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Angiography
There was characteristic obliteration of the apex of the involved ventricle(s) with varying degree of AV valve regurgitation in all patients with left ventricular or biventricular EMF (Fig 4 ). MR was severe in six patients (cases 2, 4, 16, 17, 18, and 21) [Fig 5
] and mild to moderate in five patients (cases 1, 12, 13, 19, and 20). In patients with right ventricular involvement, there was obliteration of the right ventricular apex with dilation of the outflow tract. In one patient (case 7), there was exceptional involvement of the right ventricular inflow and outflow with obliteration of the apex (Fig 6
). TR was severe in 5 patients and mild to moderate in 12 patients. Obliteration of both ventricular apices was observed in biventricular EMF. The contractility of the remaining parts of the ventricle varied from normal to severely impaired. Coronary angiographies were normal in all patients.
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Figure 5.. Left ventricular angiogram in the right anterior oblique view showing a small left ventricle with apical obliteration, severe MR, and dilated left atrium in a patient with left-sided EMF (top, a) and after surgery with endocardectomy and mitral valve replacement (bottom, b). See Figure 1 legend for expansion of abbreviations.
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Figure 6.. Right ventricular angiogram in the right anterior oblique view in a patient with right-sided EMF showing complete obliteration of the apex of the right ventricle, dilated right atrium, and severe TR. See Figure 1 legend for expansion of abbreviations.
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Endomyocardial Biopsy
Nine specimens were obtained (done during our early experience with the disease), and seven specimens showed features of EMF, namely fibrous thickening of the endocardium, made up of collagen without elastic fibers (Fig 7
). A few fibrocytes and an organized thrombus were seen in four specimens.
Follow-up
Twelve patients opted for medical treatment (mainly vasodilators), with hemodynamic improvement in 4 patients. Four patients died, and four patients were not available for follow-up. Nine patients underwent surgery (cases 2, 4, 5, 7, 9, 16, 17, 18, and 21), patients with left-sided EMF underwent endocardectomy with additional mitral valve replacement (cases 2 and 4), and patients with right-sided EMF underwent endocardectomy with tricuspid valve replacement (cases 5 and 7). One patient underwent cavopulmonary connection (case 9),10 three patients with biventricular EMF underwent endocardectomy with both mitral and tricuspid valve replacement (cases 16, 17, and 21), and one patient underwent endocardectomy only (case 18). One patient died immediately after surgery (case 5), one patient died 4 months after redosurgery for mitral prosthesis obstruction (case 21), and another patient died 2 years later from obstruction of the tricuspid valve prosthesis (case 17).
Presentation and Pitfalls in Diagnosis
RHD:
Nine patients (cases 2, 8, 9, 11, 12, 16, 17, 18, and 21) with initial presentation of dyspnea class III-VI and significant moderate-to-severe MR and or TR (Table 1) were referred as rheumatic valvular disease (RHD) cases. Diagnosis of EMF was favored because of the presence of normal AV valve leaflets (thickened in RHD) with papillary muscles involvement, obliteration of the apex of the ventricle(s), small or normal-size ventricle(s) with severe atrial dilation (Fig 1), and significant pulmonary hypertension with elevated ventricular end-diastolic pressure (VEDP) and atrial pressure.
CP:
Six patients (cases 5, 6, 10, 14, 15, and 20) with initial presentations of dyspnea class II-VI, ascites, hepatomegaly, edema (Table 1) with hemodynamic findings of rapid X and Y descents, and diastolic dip and plateau were referred as cases of CP. The diagnosis of EMF was favored because of: the presence of the characteristic ventricular apical obliteration, normal pericardium thickness, severely dilated atria, large A wave, early diastolic dip, and a plateau occupying the last two thirds of diastole, normal ventricular systolic pressure, elevated VEDP with elevated VEDP/ventricular systolic pressure ratio, and reversed diastolic pressure gradient across the pulmonary valve (Fig 2, 3).
Cardiomyopathy
HCM Apical Type:
Two patients (cases 1 and 19) presenting with dyspnea class III, moderate MR, and left ventricular apical obliteration by echocardiography were referred as cases of HCM. A diagnosis of EMF was favored because of the presence of apical obliteration during both systole and diastole (in HCM, apical obliteration occurs only in systole) and absence of significant ventricular hypertrophy (Fig 4).
DCM:
Two patients (cases 3 and 13) presented with dyspnea class III, summation gallop (Table 1), and cardiomegaly on CXR were referred as cases of DCM. Diagnosis of EMF was favored because of the presence of cardiomegaly on CXR, which was mainly due to severe atrial dilation with small or normal-sized ventricle(s) (dilated ventricles in DCM), and apical obliteration and normal ventricular end-diastolic volume (elevated in DCM) [Fig 5].
RCM:
One patient (case 4) presented with dyspnea class II and moderately severe MR. This patient was referred with hemodynamic findings suggestive of RCM with dip and plateau pattern, severe atrial dilation, small ventricular size, and elevated atrial and VEDP. The diagnosis of EMF was favored because of the presence of ventricular apical obliteration.
Ebstein Malformation of Tricuspid Valve:
One patient (case 7) was referred as a case of Ebstein anomaly after presentation with severe dyspnea, venous congestion, ascites, edema, right-sided S3 gallop, severe TR, and CXR finding of box-shaped cardiomegaly due to severe right atrial dilation. The diagnosis of EMF was favored because of the presence of right ventricle apical obliteration with exceptional involvement of the right ventricular inflow and outflow and huge right atrium, but with normal tricuspid valve leaflets attachment sites (Fig 6).
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Discussion
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EMF was first reported in equatorial Africa.123 We recognized this disease in the Middle East for the first time in 1980.49 It has also been recognized in other areas.1112131415 In the Middle East and Far East, the disease can mimic and be confused with the more common RVD, cardiomyopathies, and tuberculous CP. The diagnosis is made by echocardiographic examination when obliteration of the apex is noted with varying degrees of regurgitation of the AV valves and confirmed by angiocardiography, which demonstrates obliteration of the apex of one or both ventricles.16 The cause of the disease is not known. Possibly, abnormal eosinophils are involved in the pathogenesis5678 because frequently, but inconsistently, eosinophilia is found in patients with EMF, and with eosinophilic leukemia, Löffler disease,78 and helminthes-associated hypereosinophilia17 (as occurred in two of our patients with hypereosinophilic syndrome and who acquired biventricular EMF and had more progressive course [cases 16 and 21]). We believe that there are similarities and overlaps between Löffler disease and EMF in presentation, peripheral blood eosinophilia, and pathologic changes during acute endocardial eosinophilic infiltration, chronic fibrotic stages, hemodynamics, and mode of treatment with different geographic distribution (EMF occurs mainly in tropical areas, and Löffler disease is found in temperate countries). Perhaps this may be the same disease in different climates. In this article, we report on 21 EMF patients from different parts of Saudi Arabia (n = 17) Egypt (n = 3), and Syria (n = 1) who initially received a different diagnosis prior to their referral to our center. As the disease mainly presents in the tropical zone, unfamiliarity with this disease still exists; in the remaining part of this article, we will draw particular attention to some of the following characteristic and helpful findings favoring EMF diagnosis.
Echocardiography:
Obliteration of the apex of the involved ventricle is the hallmark of the disease, along with a grossly dilated atrium with a normal-sized (or mildly dilated) ventricle and thickening of the posterior left ventricular wall or anterior interventricular septum in patients with left-sided or right-sided involvement, respectively.181920 One condition that mimics right-sided EMF is Behçet disease, in which obliteration of the right ventricular apex by clot without TR may occur.21 Other conditions that may well mimic EMF are apical thrombus and the apical type of HCM, in which obliteration of the apex occurs in systole only. In the setting of clinically severe MR or TR, EMF can be suspected if there is echocardiographic evidence of a small or normal-size ventricle with a grossly dilated corresponding atrium. This finding is in contrast to rheumatic valve regurgitation, in which the involved ventricle tends to be dilated. The hugely dilated atria also help in differentiating the disease from CP and Behçet disease in which the atria tends to be of normal size. Also, the presence of normal-size ventricles on echocardiography in patients with gross cardiomegaly on CXR helps to differentiate EMF from DCM.
Hemodynamics and Angiocardiography:
In right ventricular EMF, right ventricular systolic pressure was normal with a raised end-diastolic pressure, resulting in a high end-diastolic/systolic pressure ratio (average 82% in our study), which is higher than that seen in CP.22 There was a reversed diastolic pressure gradient across the pulmonary valve.142223 It has been suggested that the reversed diastolic gradient across the pulmonary valve allows diastolic flow from the right ventricle to the pulmonary artery, but it is not certain whether this contributes significantly to cardiac output. The hemodynamic findings of biventricular EMF mimics those of CP, so the correct diagnoses were made by ventriculography demonstrating apical obliteration and normal pericardium at surgery. The left ventricular end-diastolic volume is characteristically normal, even in patients with severe MR and with high end-diastolic pressure. Increased ventricular end-diastolic volume in patients with poor ventricle and severe hypokinesia of the remaining ventricle represents a very late (probably terminal) stage of the disease.
Endomyocardial Biopsy:
If correctly performed, this will show features of EMF, namely fibrous thickening of the endocardium made up of collagen, fibrocytes, and occasionally organized thrombus.24 We believe that as echocardiographic and angiocardiographic findings are definitive,16 biopsy is not essential for diagnosis.
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Conclusion
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EMF does occur outside the tropical zones. It mimics RHD, CP, cardiomyopathies, and Ebstein malfunction of the tricuspid valve. Echocardiography is helpful in its recognition, and ventricular angiography is diagnostic. Endomyocardial biopsy is not essential in the diagnosis of EMF.
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Footnotes
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Abbreviations: CP = constrictive pericarditis; CXR = chest radiography; DCM = dilated cardiomyopathy; EMF = endomyocardial fibrosis; HCM = hypertrophic cardiomyopathy; MR = mitral regurgitation; NYHA = New York Heart Association; RCM = restrictive cardiomyopathy; RHD = rheumatic heart disease; TR = tricuspid regurgitation; VEDP = ventricular end-diastolic pressure
Received for publication December 27, 2005.
Accepted for publication June 2, 2005.
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References
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- Pieretti, OH Echocardiographic diagnosis and evaluation of cardiomyopathies: idiopathic hypertrophic subaortic stenosis; Chaga’s heart disease and endomyocardial fibrosis. Postgrad Med J 1977;53,533-536[Abstract]
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- Acquatella, H, Schiller, NB, Puigbo, JJ, et al Value of two-dimensional echocardiography in endomyocardial disease with and without eosinophilia. Circulation 1983;67,1219-1226[Abstract/Free Full Text]
- El Ramahi, KM, Fawzy, ME, Sieck, JO, et al Cardiac and pulmonary involvement in Behçet disease. Scand J Rheumatol 1991;20,373-376[ISI][Medline]
- Somers, K, Brenton, DP, D’Arbela, PG, et al Hemodynamic features of severe endomyocardial fibrosis of the right ventricle including comparison with constrictive pericarditis. Br Heart J 1968;30,322-331[Free Full Text]
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Abstract
Introduction
