|INTERESTING CASE REPORT
|Year : 2023 | Volume
| Issue : 1 | Page : 37-43
Extended Role of Parametric Mapping with Cardiac Magnetic Resonance in the Evaluation of Endomyocardial Fibrosis – Our Initial Experience
Sneha Hemantkumar Thakur1, Priya Darshan Chudgar2, Nikhil Kamat2, Nitin Burkule3
1 Department of Radiology, Bethany Hospital, Thane, Maharashtra, India
2 Department of Radiology, Jupiter Hospital, Thane, Maharashtra, India
3 Department of Cardiology, Jupiter Hospital, Thane, Maharashtra, India
|Date of Submission||14-Jun-2022|
|Date of Decision||30-Aug-2022|
|Date of Acceptance||16-Sep-2022|
|Date of Web Publication||28-Nov-2022|
Dr. Sneha Hemantkumar Thakur
305-306, Happiness City of Joy, JS Dossa Road, Mulund West, Mumbai - 400 080, Maharashtra
Source of Support: None, Conflict of Interest: None
Endomyocardial fibrosis (EMF) affects approximately 12 million persons worldwide and is an important cause of restrictive cardiomyopathy in the developing world, with the highest prevalence reported in sub-Saharan Africa, South Asia, and South America. EMF is characterized by apical infiltration with fibrotic tissue in one or both ventricles, often associated with thrombus in early stage of the disease, calcification in late stage of the disease, and typical symptoms of restrictive heart failure. Clinical evaluation, transthoracic echocardiography, and characteristic Doppler findings of restrictive physiology are sufficient to diagnose EMF in most of the cases. However, few cases may require cardiac magnetic resonance due to poor echo window or shadowing due to apical calcification. Tissue characterization ability of cardiac magnetic resonance imaging has evolved further in the era of parametric mapping. We plan to showcase the incremental value of parametric mapping (T1/T2 mapping) in staging, prognostication, and management in two cases of EMF.
Keywords: Cardiac magnetic resonance, endomyocardial fibrosis, T1 and T2 parametric mapping
|How to cite this article:|
Thakur SH, Chudgar PD, Kamat N, Burkule N. Extended Role of Parametric Mapping with Cardiac Magnetic Resonance in the Evaluation of Endomyocardial Fibrosis – Our Initial Experience. J Indian Acad Echocardiogr Cardiovasc Imaging 2023;7:37-43
|How to cite this URL:|
Thakur SH, Chudgar PD, Kamat N, Burkule N. Extended Role of Parametric Mapping with Cardiac Magnetic Resonance in the Evaluation of Endomyocardial Fibrosis – Our Initial Experience. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2023 [cited 2023 May 29];7:37-43. Available from: https://jiaecho.org/text.asp?2023/7/1/37/362192
| Introduction|| |
Endomyocardial fibrosis (EMF) is characterized by fibrotic infiltration of the endocardium of ventricular apices. Although EMF can result from hypereosinophilic syndrome (HES), an idiopathic variety is endemic in the tropical and subtropical regions of the world., EMF is estimated to be the most common form of restrictive cardiomyopathy in the developing world and is responsible for 20% of cases of heart failure in the endemic areas of Africa.,,
In tropical EMF, it has been hypothesized that several factors such as eosinophilia, parasitic infestations, autoimmunity, genetic predisposition, poverty, malnutrition, and environmental exposure may be acting in concert as triggers of inflammation or immunomodulation, inducing a profibrotic state in the endocardium., In Loeffler's endocarditis, cardiotoxic effect of eosinophilic granulocytes is shown to be the major pathogenetic contributor of endocardial injury and fibrosis.
Transthoracic echocardiography (TTE) with Doppler is always the first-line modality for the diagnosis of EMF. Cardiac magnetic resonance (CMR) with its capability of assessment of cardiac morphology and function along with tissue characterization can have incremental value in staging the disease process as described below.
| Case Report|| |
We present here two cases of EMF who had presented to us in different clinical stages of the disease.
A 45-year-old male presented with impaired exercise tolerance and shortness of breath [New York Heart Association (NYHA) Class III] over the past 1 month. The patient was nondiabetic and nonhypertensive. There was no history of allergies or asthma. He had a history of multiple cerebral and cerebellar infarcts. On examination, there was no fever or tachycardia. Electrocardiogram (ECG) revealed asymmetric T-wave inversion and ST depression in inferior and lateral leads suggestive of left ventricular (LV) strain pattern [Figure 1]. Inflammatory markers were mildly elevated. Troponin I was significantly elevated (2.615 ng/mL). Complete blood count revealed hypereosinophilia with absolute eosinophil count of 4700 per microliter. Serum immunoglobulin E levels were also markedly elevated (>3000 IU/mL).
|Figure 1: Case 1: Electrocardiogram revealed asymmetric T-wave inversion and ST depression in inferior and lateral leads suggestive of left ventricular strain pattern|
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Two-dimensional echocardiography demonstrated a triangular echogenic mass filling the LV apex with preserved contractility of the underlying myocardium [Figure 2]a and [Video 1]. Myocardial contrast echocardiography showed no contrast uptake in the LV apical mass, consistent with a clot. However, there was good contrast enhancement of the underlying apical myocardial segments [Figure 2]b; [Video 2].
|Figure 2: Case 1: (a) Echocardiography revealing echogenic mass obliterating the LV apex. (b) Myocardial contrast echocardiography showing no contrast uptake in the LV apical clot with contrast enhancement of underlying apical myocardial segments. LV: Left ventricular|
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[Additional file 1]
Video 1: Echocardiography revealing echogenic mass obliterating the left ventricular apex.
[Additional file 2]
Video 2: Myocardial contrast echocardiography showing no contrast uptake in the left ventricular apical clot with contrast enhancement of the underlying apical myocardial segments.
In view of hypereosinophilia, a diagnosis of EMF due to Loeffler's endocarditis was considered and CMR was suggested for tissue characterization.
Cardiac magnetic resonance protocol
ECG-gated CMR examination was performed on Siemens Verio 3 Tesla Scanner System with adequate breath hold using both anterior and posterior array coils. Segmented acquisition of 25 phases of cardiac cycle was obtained for each long-axis and short-axis view. Complete examination with cine images in three long-axis and six short-axis views, flow imaging of aorta, and pulmonary artery with phase-contrast sequences and late gadolinium enhancement (LGE) imaging using phase-sensitive inversion recovery sequences was performed. T1 parametric mapping was performed using the Shortened MOdified Look-Locker Inversion recovery sequence before and after contrast administration. T2 parametric mapping was also done prior to contrast injection. Three short-axis slices (base, mid, and apex) and one four-chamber view were obtained for complete assessment. Hematocrit was obtained on the day of the study and extracellular volume fraction (ECV) was calculated. Postprocessing was performed using commercially available dedicated CMR postprocessing software suiteHEART®, NeoSoft LLC, Wisconsin, USA.
The cine steady-state free precession (SSFP) images revealed normal LV contractility with no evidence of regional wall motion abnormality. The presence of filling defect was observed at LV apex with concave surface toward the LV cavity. The hyperintense signal of the apical mass [Figure 3], [Video 3] was distinct from the surrounding myocardium suggesting a fresh clot.
|Figure 3: Case 1: Two-, four-, and three-chamber views showing filling defect at the left ventricular apex having slightly higher signal intensity as compared to the myocardium on the steady-state free precession sequence|
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[Additional file 3]
Video 3: Two-, four-, and three-chamber view showing filling defect at the left ventricular apex having slightly higher signal intensity as compared to myocardium on steady-state free precession sequence.
Precontrast T1 mapping showed myocardium with diffusely increased T1 values (1393 ± 65 ms; normal values = 1150 ± 50 ms for the scanner) which suggested myocardial fibrosis or edema. The central portion of the apical clot showed T1 values of 679 ms which was significantly lower than the adjacent myocardium suggesting heme degradation products [Figure 4]a. T2 mapping value of the myocardium was normal and the T2 value of the clot was low (39.3 ± 2 ms) due to heme degradation products [Figure 4]b.
|Figure 4: Case 1: (a) Native T1 mapping in the four-chamber view depicting elevated T1 value of the myocardium with low T1 value of the central portion of the clot due to paramagnetic effect of heme-rich clot contents. Blue ROI represents T1 time of the myocardium = 1393 ± 65. Green ROI represents T1 time of margin of the clot = 960 ± 113. Red ROI represents T1 time at center of the filling defect, i.e., clot = 679 ± 49.7. (b) T2 parametric map showing the left ventricular apical filling defect having similar signal as compared to myocardium. ROI: Region of interest|
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The clot remained hypointense (avascular) in the images of first-pass gadolinium perfusion sequence [Figure 5]a. LGE images revealed typical “double V-” shaped configuration representing the classical three-layered pattern (normal myocardium, enhancing endocardium, and overlying thrombus) at the LV apex [Figure 5]b.
|Figure 5: Case 1: (a) Perfusion study showing homogenous enhancement of myocardium with apical nonenhancing area with concave margin toward the left ventricular cavity. (b) Late gadolinium enhancement images with phase-sensitive inversion recovery sequence show apical subendocardial enhancement with a nonenhancing apical filling defect (arrow shows typical double V sign)|
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LGE images with high inversion values (inversion time [TI] = 850 ms) revealed persistence of dark signal in the apical filling defect, consistent with apical thrombus [Figure 6]. On postcontrast T1 mapping, reduced T1 values were noted in the endocardium (the interface of clot and the myocardium), which correlated with pathophysiology of endocardial inflammation, increased ECV resulting in contrast accumulation, and reduced T1 values [Figure 7]. The calculated myocardial ECV (excluding the clot) was elevated (29.9%).
|Figure 6: Case 1: Phase-sensitive inversion recovery images acquired with high inversion time of 850 ms show hypointense filling defect confirming the diagnosis of clot|
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|Figure 7: Case 1: Postcontrast T1 mapping in the four-chamber view. Red ROI represents T1 value of myocardium = 406 ± 23.5 ms. Blue ROI represents T1 value of the enhancing region at the margin of myocardium and clot = 186 ± 19.9 ms. Green ROI represents T1 value of the clot = 616 ± 48.6 ms. ROI: Region of interest|
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In view of subendocardial LGE and apical subacute clot on CMR, a diagnosis of subacute stage of EMF was considered and the patient was started on steroids and anticoagulants.
A 54-year-old female presented with shortness of breath (NYHA class III) and signs and symptoms of cardiac failure. She had a history of similar episodes with repeated admissions for congestive heart failure. ECG revealed low-voltage complexes in limb leads and asymmetric T-wave inversion and ST depression in V3-V6 [Figure 8].
|Figure 8: Case 2: Electrocardiogram revealed low-voltage complexes in limb leads and asymmetric T-wave inversion and ST depression in V3-V6|
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High-resolution computed tomography chest, performed as a part of protocol during the coronavirus disease pandemic time, demonstrated abnormal cardiac calcification [Figure 9]. TTE [Figure 10]a, [Video 4] revealed small LV cavity with significantly dilated atria suggestive of restrictive physiology. There was obliteration of the LV apical cavity with hyperechoic mass with shadowing artifacts due to apical calcification. There was no valvular regurgitation. Myocardial contrast echocardiography showed contrast enhancement of the LV apical myocardial segments with shadowing of the LV cavity due to calcification [Figure 10]b, [Video 5].
|Figure 9: Case 2: Computed tomography revealing extensive cardiac calcification. Bilateral pleural effusions are also seen as the patient was in congestive cardiac failure|
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|Figure 10: Case 2: (a) Echocardiography revealing small LV cavity with hyperechoic contents at the apex with acoustic shadowing due to calcification. (b) Myocardial contrast echocardiography showing contrast enhancement of LV apical myocardial segments with shadowing of the LV cavity due to calcification. LV: Left ventricular|
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[Additional file 4]
Video 4: Echocardiography revealing small left ventricular cavity with hyperechoic contents at the apex with acoustic shadowing due to calcification.
[Additional file 5]
Video 5: Myocardial contrast echocardiography showing contrast enhancement of left ventricular apical myocardial segments with shadowing of the left ventricular cavity due to calcification.
A comprehensive diagnostic workup revealed no evidence of infection, autoimmune disease, or hematological disorder. There was no eosinophilia. Preliminary diagnosis of tropical EMF was considered. The patient was initially treated for heart failure with guideline-directed medical therapy. Further workup with CMR was suggested for prognostication.
Cardiac magnetic resonance findings
Cine SSFP images revealed apical obliteration of the LV cavity with apical filling defect isointense to adjoining myocardium [Figure 11], [Video 6]. There were areas of hypointense signals along the cavity margin of this apical filling defect which correlated with calcification on computed tomography images. Both atria were dilated and there was no valvular regurgitation.
|Figure 11: Case 2: Steady-state free precession images of four-, two-, and three-chamber views depicting apical obliteration of the left ventricular cavity with apical contents isointense to the myocardium (arrow). There is hypointense rim along the blood pool margin of the filling defect (signal loss) which corresponds to calcification at the boundary. There is dilatation of both the atria which is suggestive of restrictive physiology|
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[Additional file 6]
Video 6: Steady-state free precession images of four-, two-, and three-chamber views depicting apical obliteration of the left ventricular cavity with apical contents isointense to the myocardium (arrows). There is hypointense rim along the blood pool margin of the filling defect (signal loss) which corresponds to calcification at the boundary. There is dilatation of both the atria which is suggestive of restrictive physiology.
Native T1 mapping showed myocardium with increased T1 values (1318 ms), which were similar to the T1 values of the filling defect (1294 ms) suggestive of fibrosis [Figure 12]a. T2 values of the apical mass were similar to the myocardium [Figure 12]b.
|Figure 12: Case 2: (a) Native T1 map in the four-chamber view. Red ROI represents T1 value of the myocardium = 1318 ± 41.3 ms. Blue ROI represents T1 value of the filling defect = 1294 ± 19.0 m. (b) T2 map in the four-chamber view. Red ROI represents T2 myocardial value = 44.6 ± 0.98 m. Blue ROI represents T2 value of the filling defect = 43.8 ± 2 ms. ROI: Region of interest|
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The LV apical filling defect showed no enhancement in the images of first-pass gadolinium perfusion sequence suggesting an avascular mass [Figure 13]a. LGE images showed V-shaped three-layered pattern (nulled normal myocardium, enhancing EMF, and overlying dark calcification and avascular fibrotic mass filling the apex of the left ventricle [Figure 13]b. The calculated myocardial ECV (excluding clot) was increased (35%).
|Figure 13: Case 2: (a) First-pass perfusion images showing nonenhancing LV apical filling defect. (b) Four-chamber (left) and three-chamber (right) LGE images show mild enhancement at apical endocardium with nonenhancing region along the LV cavity corresponding to calcification (arrow shows typical double V configuration). LGE: Late gadolinium enhancement, LV: Left ventricular|
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These features of severe restrictive physiology, fibrosis and calcification of the LV apical filling defect, and absence of eosinophilia favored the diagnosis of advanced stage of long-standing tropical EMF. The patient was treated with guideline-directed medical therapy for heart failure and has been listed for cardiac transplant.
| Discussion|| |
Clinical and imaging findings are highly variable in the EMF (either tropical or HES) depending on the stage of the disease. The eosinophil-mediated heart damage in EMF evolves through the three stages, although these might be overlapping and not clearly sequential.
- Stage 1: Acute endomyocardial inflammation/necrosis (first 1–2 months) resulting from eosinophilic infiltration with degranulation and release of toxic proteins. Acute febrile illness associated with constitutional symptoms and clinical signs of pancarditis may be present. This stage is characterized by pericardial effusion, myocardial edema, subendocardial necrosis, eosinophilic infiltration, and vasculitis but no fibrosis,
- Stage 2: Subacute or thrombotic stage (after about 10 months) resulting from endocardial damage and overlying thrombus formation. Subendocardial infarction, valve motion restriction, and thromboembolic events may occur,
- Stage 3: Fibrotic stage (after 1–2 years) in which the thrombi are replaced by fibrosis. The endocardium, valves, and chordae tendineae may get involved in the fibrotic process. This stage is characterized by progressive endocardial scarring and restrictive filling pattern with atrioventricular valve regurgitation. However, there is no myocardial inflammatory exudate or eosinophilia, implying that the inflammatory process is inactive.
CMR can be utilized for the evaluation of morphologic features of EMF and includes assessment of LV and left atrial volumes and function, valvular regurgitation, and the presence of apical filling defect. SSFP images are ideal for the assessment of ventricular volume, mass, and function as well as pleural and pericardial effusions., In addition, these sequences are also useful for the evaluation of typical restrictive physiology of EMF such as bi-atrial dilatation, apical obliteration of the LV, and right ventricle apex.
The parametric mapping may be useful in the staging of the disease. T1- and T2-mapping values of myocardium will estimate interstitial fibrosis and edema, respectively, while the native and postcontrast T1 mapping values of the apical filling defect can provide a clue to its composition. The pre- and postcontrast T1 values of blood and myocardium along with the hematocrit are used to calculate the myocardial ECV.
In the early stages of the disease, there may not be any significant identifiable feature on the cine images. The myocardial edema, however, is present and can easily be detected on T2 mapping [Table 1]. The presence of subendocardial LGE is suggestive of inflammatory exudate in the subendocardium causing expansion of the extracellular space. However, very few cases are subjected to CMR at this stage due to the paucity of symptoms. At this stage, the ECV increase has been demonstrated to be an indicator of disease burden and a prognostic marker.
|Table 1: Role of cardiac magnetic resonance in detecting the various stages of endomyocardial fibrosis|
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With time, as the disease evolves into a subacute phase, there is a red blood cell (RBC)-rich (red) clot formation along the damaged subendocardial surface. The patients may present with breathlessness due to restrictive physiology or embolic infarcts. CMR is usually performed in subacute or chronic phase.,
Circulating blood is composed of plasma and cellular elements. Plasma is mostly water and thus has relatively long T1 and T2 values. In the subacute stage of the clot, there is RBC lysis leading to extracellular heme and heme degradation products. The iron-rich heme degradation products have low T1 and T2 values compared to myocardium. The presence of heme/iron-rich contents in the apical thrombus lowers the T1 value in apical filling defect making the distinction between the myocardium and the clot obvious on precontrast T1 map. This is of immense value as these variations in T1 time of the tissue help in characterization of the contents in the absence of gadolinium contrast.
Postcontrast T1 maps demonstrate subendocardial inflammation as gadolinium is retained within the expanded subendocardial extracellular space lowering the T1 value. The absence of enhancement in the apical mass is consistent with the avascular nature of the clot which remains dark on high TI images.
The presence of subendocardial LGE and heme product- rich apical clot are suggestive of active pathology and hence patients need to be promptly treated with corticosteroids/immunomodulators to arrest the eosinophil- mediated inflammation. Anticoagulation may be considered in those with acute/subacute clot or atrial fibrillation and in those with a history of thromboembolic events. Follow-up CMR may have a role in deciding the treatment duration, guided by resolution of the inflammation and the clot.
Chronic organized thrombi are more difficult to differentiate, as they may have similar signal intensity as that of myocardium on SSFP images because of low water content, fibrosis, and calcification. In our second case, T1 value of the apical filling defect was similar to the myocardium in the native T1 map. At this stage, the T2 map does not have a role to differentiate fibrosis/clot from the myocardium.
In chronic phase, there is presence of calcification along the LV cavity margin as seen in our second case. The imaging features at this stage are dominated by bi-atrial dilatation, signs of pulmonary hypertension, and pleural and pericardial effusions with relatively preserved ventricular systolic function. There is no imaging evidence of ongoing inflammation; hence, there is no role of immunomodulators or steroids. Treatment is thus limited to symptomatic relief of the heart failure with diuretics to reduce systemic and venous congestion and control of atrial arrhythmias. These patients progress to refractory heart failure and are poor responders to optimal medical therapy. Surgical stripping of the LV apical fibrous content has been described by experienced centers.
Long-term prognosis for advanced chronic EMF is poor, with 75% mortality at 2 years. Death may be caused by progressive heart failure or sudden cardiac death secondary to ventricular arrhythmias or pulmonary thromboembolism.
| Conclusion|| |
Clinical and imaging findings are highly variable in EMF depending on the stage of the disease. CMR can be utilized as a comprehensive tool for diagnosis, staging, risk stratification, and guiding the treatment. T1 and T2 parametric mapping adds value with its tissue characterization capability. It provides noninvasive assessment of the contents of ventricular apical filling defect (subacute red thrombus vs. organized fibrotic/calcified mass) and estimates the extent of active subendocardial inflammation and fibrosis. This additional diagnostic information may guide the medical management and improve the clinical outcome.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13]