Endomyocardial Fibrosis: A Possible Rare Etiology of Intracavitary Thrombi and Heart Failure

Doris Licely Canché Aguilar, Diego Leonardo Meza Neri, Sandra Graciela Rosales Uvera

National Institute of Medical Sciences and Nutrition Salvador Zubirán, Mexico City, Mexico

Clinical History

A 23-year-old male with a history of chronic diarrhea due to Trichuris trichiura presented to the emergency department with New York Heart Association (NYHA) class III dyspnea on minimal exertion, paroxysmal nocturnal dyspnea, and orthopnea. Two years prior, he presented with an ischemic stroke. As part of the initial diagnostic workup, a transesophageal echocardiogram was performed, revealing a patent foramen ovale (PFO), with a left ventricular ejection fraction (LVEF) of 43%, and a tricuspid annular plane systolic excursion (TAPSE) of 25 mm with no intracardiac thrombi. Percutaneous closure of the PFO was performed with an Amplatzer Talisman PFO Occluder (Abbott Medical, Chicago, IL, USA) device. Post-procedural echocardiography reported right-sided chamber dilation, an improved LVEF of 63%, and decreased TAPSE of 16 mm. At discharge, the patient was started on aspirin and clopidogrel.
 
At the current evaluation, a chest X-ray was performed, showing cardiomegaly (Figure 1). An echocardiogram revealed biventricular dysfunction with a LVEF of 28%, a TAPSE of 9 mm, and multiple intracavitary thrombi. Medical treatment was initiated with rivaroxaban, bisoprolol, spironolactone, enalapril, and furosemide. A thrombophilia workup was conducted (PCR for Factor V Leiden: negative; protein C activity: decreased [41.4%]; activated protein C resistance: negative; PCR for Factor II: negative).
A complete blood count reported: leukocytes 4.4 x 10^3/μL (normal 4.5-11.0 10^3/μL), eosinophils 0.3% (normal 1-4%), basophils 1.0% (normal 0.5-1.0%), neutrophils 62.3% (normal 40-60%), monocytes 5.4% (normal 2-8%), lymphocytes 31.0% (normal 20-40%).
The diagnostic workup was completed with a cardiac magnetic resonance (CMR) study.

Figure 1. Posteroanterior chest x-ray. A markedly enlarged cardiac silhouette is observed with a cardiothoracic ratio of 0.69 and a bottle-shaped morphology

CMR Findings

CMR was performed on a 1.5T Signa HDxt scanner (GE HealthCare, Chicago, Illinois) using cine steady-state free precession (SSFP) sequences for the evaluation of anatomy and function. The images demonstrated a mildly dilated left ventricle (LV) with a left ventricular end-diastolic volume index (LVEDVi) of 97.3 mL/m² with severe global hypokinesia (LVEF 8%) and septal flattening, consistent with right ventricular volume overload presumably secondary to severe tricuspid valve regurgitation. The right ventricle (RV) was severely dilated (the right ventricular end-diastolic volume index (RVEDVi) was 152.9 mL/m²) with severe hypokinesia of the free wall (right ventricular ejection fraction (RVEF) of 14%) (Movie 1 and 2). Additionally, the right atrium was dilated, with a thrombus measuring 32 x 29 mm attached to the atrial roof and another thrombus in the apex of the LV measuring 28 x 28 mm. Mild mitral regurgitation and severe tricuspid regurgitation were observed. A thrombus measuring 68 x 18 mm was identified in the apex of the RV. A moderate global pericardial effusion was noted with a maximal separation of the pericardial layers (visceral and parietal) of 18 mm.

Movie 1. Balanced cine SSFP short axis stack. There is severe RV and LV hypokinesia with masses in the right and left ventricles. There is ventricular septal flattening during diastole consistent with RV volume overload.

Movie 2. Balanced cine SSFP LV two (A), LV three (B), four chamber (C), and RV three chamber (D) views. Dilated right atrium and ventricle with masses present in both chambers.  There is severely decreased bi-ventricular systolic function. Mass in the LV apex

For tissue characterization, T2-weighted, T1-weighted, black blood T1-weighted imaging with and without fat saturation, perfusion, and T1 gradient recalled echo inversion recovery (GRE IR) sequences were performed (Figure 2). In the perfusion sequence, no uptake was observed in the intracavitary masses, and the post-contrast T1 sequence with a 500 ms inversion time confirmed the presence of thrombi (Movie 3). The late gadolinium enhancement study revealed a pattern of subepicardial fibrosis in the anteroseptal and inferoseptal basal and mid segments, apical septal, anterolateral and inferolateral basal and mid segments, as well as the apex. Subendocardial enhancement was also identified in the mid inferior segment (Figure 3). In the four-chamber view, the post-contrast T1 sequence demonstrated the characteristic “double V” sign, highly suggestive of endomyocardial fibrosis (Figure 4)

Figure 2. T2 weighted (A), T1 weighted without fat saturation (B) and with fat saturation (C), four chamber perfusion (D), post-contrast GRE IR four chamber (E) and short axis (F). The masses in the atrium and ventricle are hyperintense on T2 and T1 weighted without and with fat saturation and hypointense on perfusion and GRE IR sequences

Movie 3. Perfusion four chamber. There is no uptake of contrast of the masses in the right atrium, right ventricle, or left ventricle

Figure 3. Post contrast GRE IR short axis stack. Subepicardial late gadolinium enhancement (LGE) in the anteroseptal and inferoseptal basal and mid segments, apical septal, anterolateral and inferolateral basal and mid segments, and the apex. Subendocardial LGE was noted in the mid inferior segment. The multiple ventricular masses are hypointense

Figure 4. Post contrast GRE IR four chamber view. The atrial and ventricular masses are hypointense. The “double V” sign (arrows) is present with subendocardial LGE in a “V” pattern in the apex of the RV and LV.

 

Conclusion

These findings supported the likely diagnosis of endomyocardial fibrosis (EMF). Loeffler’s endocarditis or eosinophilic endomyocarditis was ruled out, as the absolute eosinophil count remained consistently within normal limits throughout follow-up (0.3%). [1] Cases of EMF without eosinophilia have been reported, and it remains possible that transient eosinophilia may have occurred and resolved prior to clinical evaluation.[2,3] Arrhythmogenic cardiomyopathy was also considered among the differential diagnoses. However, the patient had no first-degree family history of the disease or premature sudden cardiac death. He did not present with arrhythmias, and the characteristic “striped” pattern of late gadolinium enhancement was not identified. Based on these findings, and using the Padua criteria, this diagnosis was ruled out.[4]
 
Cardiac sarcoidosis was another differential diagnosis considered, as the pattern of late gadolinium enhancement in our patient can also be seen in this condition. However, no granulomas were identified on thoracic imaging. Furthermore, the patient did not exhibit conduction abnormalities, and the presence of intracavitary thrombi helped to rule out this etiology, since thrombi are not a common finding in this form of cardiomyopathy. Optimal medical therapy for heart failure was initiated. Although the patient was evaluated as a candidate for heart transplantation, he unfortunately died during hospitalization.
 

Perspective

EMF is a significant cause of restrictive cardiomyopathy, characterized by apical fibrosis of one or both ventricles, thrombus formation, calcifications, and atrioventricular valve regurgitation, ultimately leading to heart failure.[5] Helminth-induced hypereosinophilia has been associated with tropical EMF. Filariae and schistosomiasis are the most commonly implicated nematodes. The proposed immunopathogenesis suggests that persistent eosinophilia leads to eosinophil activation and subsequent tissue damage, resulting in endomyocardial fibrosis. Clinically, tropical EMF mimics idiopathic hypereosinophilic syndrome with cardiac involvement, leading to fibrosis, mural thrombus, arrhythmias, and in some cases, pericarditis with effusion. The prognosis is poor, with death frequently resulting from chronic heart failure and its complications.[6]

The specific etiologic factor responsible for the development of EMF in this patient remains unknown. Proposed theories aim to explain the distinct geographic and pathological patterns of the disease.[7] The pathological hallmark of established EMF is focal or diffuse endocardial thickening, involving both ventricles in 50% of cases, and only the left ventricle in 40%. The remainder affects the right ventricle alone. The hallmark characteristic of the condition is the fibrotic obliteration of the affected ventricle. The underlying process produces focal or diffuse endocardial thickening and fibrosis, which leads to restrictive physiology.

Myocardial fibrosis consists of collagen deposition and fibroblast proliferation. Changes in collagen composition and an abnormal increase in its concentration (a selective increase in type I collagen) result in a stiffer myocardium and ventricular diastolic dysfunction. It’s pathology resembles conditions such as eosinophilic cardiomyopathy and hypereosinophilic syndrome.

In the LV, the fibrosis typically extends from the apex to the posterior leaflet of the mitral valve, sparing the anterior mitral valve leaflet and the left ventricular outflow tract. Furthermore, the fibrosis in some cases can involve the papillary muscles and chordae tendineae resulting in atrioventricular valve regurgitation and distortion. Microscopically there is deposition of dense fibrous tissue in the sub-endocardium with superimposed thrombosis and calcification in advanced stages.[7]

The CMR provides unique tissue characterization capabilities. LGE serves as a cornerstone technique, enabling precise localization and quantification of fibrotic areas, thereby offering both diagnostic and prognostic information.[8] LGE imaging is fundamental in myocardial tissue characterization and allows for the identification of myocardial fibrosis. In cases of EMF, a characteristic pattern known as the “double V sign” may be observed. This pattern involves three distinct layers: normal myocardium, thickened and hyperenhanced endomyocardium, and an overlying thrombus at the apex of the affected ventricle. This finding correlates well with histopathological observations and plays a crucial role in distinguishing EMF from other cardiomyopathies.[9] Moreover, the burden of fibrotic tissue as quantified by LGE—especially when indexed to body surface area—has been shown to be a powerful independent predictor of mortality.[10]

Pharmacologic therapy for mild-to-moderate EMF includes diuretics, renin-angiotensin system inhibitors, digoxin, β-blockers, anticoagulants, and corticosteroids. Although optimal medical management improves general clinical status and alleviates heart failure symptoms in most patients, some succumb to refractory heart failure or acute pulmonary thromboembolism.[11]

Click here for a link to the entire CMR on CloudCMR.

 

References

1. Brambatti M, Matassini MV, Adler ED, Klingel K, Camici PG, Ammirati E. Eosinophilic myocarditis: characteristics, treatment, and outcomes. J Am Coll Cardiol. 2017;70(19):2363–2375. doi:10.1016/j.jacc.2017.09.005
2. Corrado D, Zorzi A, Cipriani A, Bauce B, Bariani R, Beffagna G, De Lazzari M, Migliore F, Pilichou K, Rampazzo A, Rigato I, Rizzo S, Thiene G, Perazzolo Marra M, Basso C. Evolving Diagnostic Criteria for Arrhythmogenic Cardiomyopathy. J Am Heart Assoc. 2021 Sep 21;10(18):e021987.
3. Madi D, Achappa B, Pai N, Kamath P. Right ventricular endomyocardial fibrosis – A case report. Australas Med J. 2013;6(2):88-90.
4. Laher S, Wong YW, Platts D, Prabhu A, Thomson B, Hamilton-Craig C, Godbolt D, Cheesman E, Dashwood A. A Rare Case of Severe Nontropical Isolated Right Ventricular Endomyocardial Fibrosis. JACC Case Rep. 2020 Nov 18;2(13):2078-2084.
5. Scatularo CE, Salgado LA, Fernández M, Maldonado J. Endomyocardial fibrosis: a systematic review. Curr Probl Cardiol. 2021;46(4):100784.
6. Hidron AI, Vogenthaler N, Santos-Preciado JI, Rodríguez-Morales AJ, Franco-Paredes C, Rassi A Jr. Cardiac involvement with parasitic infections. Clin Microbiol Rev. 2010;23(2):324–349.
7. Rodrigues EA, Mocumbi AO, Ferreira MB. Endomyocardial fibrosis: past, present, and future. Heart Fail Rev. 2020;25(5):725–730.
8. Velandia-Carrillo C, Herrera C, Rodríguez-Diez G, Alfonso M, Lozano-Garcia J, Castro-Fuentes C. Multimodality imaging in endomyocardial fibrosis: an unusual etiology of heart failure. JACC Case Rep. 2020;2(13):2095–2100.
9. Carvalho A, Azevedo CF. Comprehensive assessment of endomyocardial fibrosis with cardiac MRI: morphology, function, and tissue characterization. RadioGraphics. 2020;40(2):336–353. 
10. Goyal P, Weinsaft JW. Cardiovascular magnetic resonance imaging for assessment of cardiac thrombus. Methodist Debakey Cardiovasc J. 2013;9(3):132–136.
11. Mocumbi AO, Ferreira MB, Yacoub MH. Endomyocardial fibrosis: an update after 70 years. Curr Cardiol Rep. 2019

 

Case prepared by:
Jason N. Johnson, MD MHS
Editor-in-Chief, Cases of SCMR
Le Bonheur Children’s Hospital, The University of Tennessee Health Science Center, St. Jude Children’s Research Hospital