Multimodality Imaging Clues for Restrictive Cardiomyopathy

Srilakshmi M Adhyapak; Grace A Thomas; Anuraag Gupta; Jabraan U Shaikh; Tivlin Jose; Harshith Kramadhari; Kiron Varghese

doi:10.4103/jiae.jiae_55_21

INTERESTING CASE REPORT

Year : 2022 | Volume : 6 | Issue : 2 | Page : 134-137

Multimodality Imaging Clues for Restrictive Cardiomyopathy

Srilakshmi M Adhyapak¹, Grace A Thomas¹, Anuraag Gupta¹, Jabraan U Shaikh¹, Tivlin Jose¹, Harshith Kramadhari², Kiron Varghese¹
¹ Department of Cardiology, St. John's Medical College Hospital, Bengaluru, Karnataka, India
² Department of Radiology, St. John's Medical College Hospital, Bengaluru, Karnataka, India

Date of Submission	14-Sep-2021
Date of Acceptance	13-Nov-2021
Date of Web Publication	01-Feb-2022

Correspondence Address:
Dr. Srilakshmi M Adhyapak
Department of Cardiology, St. John's Medical College Hospital, Bengaluru - 560 034, Karnataka
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jiae.jiae_55_21

Abstract

Restrictive cardiomyopathy is an entity that can be mistaken for several mimicking conditions, including hypertrophic cardiomyopathy. These patients present with heart failure, which is essentially due to left ventricular diastolic dysfunction, with preserved left ventricular ejection fraction. Conditions associated with hypereosinophilia and diastolic dysfunction with restrictive heart disease are called Loeffler's syndrome. There is also associated left ventricular thrombus formation and fibrosis. Here, we present a case of restrictive cardiomyopathy associated with rheumatoid arthritis presenting clinically with heart failure. The clues pointing toward hypereosinophilic endocarditis were a high absolute eosinophil count and a large left ventricular thrombus. We discuss the multimodality imaging findings to differentiate the different types of restrictive cardiomyopathy.

Keywords: Heart failure, left ventricle, restrictive cardiomyopathy

How to cite this article:
Adhyapak SM, Thomas GA, Gupta A, Shaikh JU, Jose T, Kramadhari H, Varghese K. Multimodality Imaging Clues for Restrictive Cardiomyopathy. J Indian Acad Echocardiogr Cardiovasc Imaging 2022;6:134-7

How to cite this URL:
Adhyapak SM, Thomas GA, Gupta A, Shaikh JU, Jose T, Kramadhari H, Varghese K. Multimodality Imaging Clues for Restrictive Cardiomyopathy. J Indian Acad Echocardiogr Cardiovasc Imaging [serial online] 2022 [cited 2023 Sep 27];6:134-7. Available from: https://jiaecho.org/text.asp?2022/6/2/134/337108

Introduction

Systemic diseases such as amyloidosis and Fabry disease can infiltrate the myocardium and lead to restrictive heart disease. Loeffler's endocarditis (and the related endomyocardial fibrosis), is a rare type of restrictive cardiomyopathy which is frequently accompanied by peripheral eosinophilia, which may be idiopathic or associated with helminthic infection in the tropics. The hallmark of this condition is the formation of diffuse thrombi in the endocardium in one or both left ventricle (LV) apices that may embolize and can grow large enough to obliterate the cavities.^[1] Here, we discuss the possible imaging clues to identify the underlying pathology in the setting of restrictive cardiomyopathy.

Clinical Presentation

A normotensive and euglycemic 34-year-old female presented with the complaints of cough, fever, and exertional dyspnea at New York Heart Association (NYHA) grade II of 1-month duration. She had been diagnosed with seropositive rheumatoid arthritis since 2016, for which she was on regular medication with methotrexate, hydroxychloroquine, and low-dose steroids. She had no relevant family history.

Clinical examination revealed sinus tachycardia (heart rate: 130/min) with a blood pressure of 110/70 mmHg and a saturation of 96% on room air. There were no signs of pallor, icterus, cyanosis, clubbing, lymphadenopathy, or pedal edema. Her jugular venous pressure was elevated (8 cm). There was “swan neck deformity” of the right fourth digit and hyperextension of the left second, third, and fourth proximal interphalangeal joints. Cardiovascular examination revealed the presence of an S4 in addition to the normal heart sounds. There were no murmurs. The respiratory examination showed normal vesicular breath sounds bilaterally. There was no organomegaly and no neurological deficit.

Workup

The routine blood tests revealed anemia (hemoglobin 10 g/dL), leukocytosis (total count 30,000 cells/mm³⁾, hypereosinophilia (69% of total white cell count, absolute eosinophil count 20,700 cells/mm³), decreased platelet count (150,000 cells/mm³), markedly elevated N-terminal pro B-type natriuretic peptide (10,200 ng/L), and an elevated troponin I of 0. 073 ng/mL. Antinuclear antibody positivity was noted (3+) with anti-cyclic citrullinated peptide being 151.6 U/mL, consistent with rheumatoid arthritis. The serum iron level was low (37 μg/dL). C-reactive protein was mildly elevated (3.05 mg/dL), and the erythrocyte sedimentation rate was 4 mm/h. Her blood glucose, glycosylated hemoglobin and liver and renal function tests were normal. As the patient had anemia, thrombocytopenia and eosinophilia, a hematology consultation was obtained. A bone marrow aspiration and biopsy, serum immunofixation, molecular tests, and free light chain assay were advised. The bone marrow aspiration and biopsy showed a cellular marrow with an increase in eosinophils and megakaryocytes. Serum electrophoresis was done, which showed hypoalbuminemia with increased alpha 1 globulins and decreased beta1 globulins.

The cardiac evaluation demonstrated sinus tachycardia, left atrial enlargement, and no evidence of left ventricular hypertrophy on electrocardiography (ECG).

Transthoracic echocardiogram was done using GE Vivid 7 machine (GE Health care, Wisconsin, Ill) and showed an LV ejection fraction of 56%. The basal interventricular septum (IVS) and LV posterior wall appeared thickened (16 mm) because of a layered thrombus but there was no true hypertrophy (IVS thickness 9 mm) [Video 1]a. This caused severe restriction of mitral valve leaflets at their annular attachment leading to functional mitral stenosis (mitral valve peak pressure gradient/mean pressure gradient = 48/29 mmHg) [Video 1]b. The color Doppler and continuous wave Doppler did not show any mitral regurgitation. There was severe pulmonary hypertension (pulmonary artery systolic pressure = 62 mmHg) with preserved LV systolic function. The LV strain mapping demonstrated relatively preserved apical strain with reduced strain in the basal septum, inferior wall, and posterior wall [Figure 1].

Figure 1: Left ventricular longitudinal strain bull's eye plot showing reduced strain in the basal septum, inferior, and posterior walls

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Video 1: [Additional file 1](a and [Additional file 2]b) Apical four-chamber view during echocardiography. The mitral valve inflow shows turbulent color flow with increased gradients.

The parasternal long-axis view and four-chamber view demonstrate the hypertrophy of the basal portion of the left ventricle along with the layered thrombus within. The thrombus is seen mainly on the inferior wall and at the left ventricle base. The mitral valve restriction is seen.

Two-dimensional (2D) echocardiography did not show any evidence of myocardial speckling. There were no hyperechoic areas in the LV endocardium and myocardium, making fibrosis and scarring less likely. There was no hypertrophy of the IVS, making the possibility of hypertrophic cardiomyopathy less likely.

To further evaluate this possibly infiltrative cardiomyopathy, a cardiac magnetic resonance (CMR) imaging was done using SIGNAArchitect AIR Edition GE 3.0 T United States, which revealed normal LV wall thickness with restricted diastolic expansion [Figure 2]a and [Figure 2]b. There was poor suppression of myocardium on T1 inversion recovery sequences. The myocardium was seen suppressing after spleen and LV blood pool, suggesting a possibility of infiltrative heart disease^[2] [Video 2]a. In short tau inversion recovery (STIR) sequences, myocardial hyperintensity was noted in the anteroseptal and septal areas in the basal and mid-cavity segments suggesting myocardial inflammation [Figure 2]d. There was reduced signal intensity of the endocardium. Postcontrast sequences showed diffuse subendocardial enhancement of the atrial wall, IAS, and LV and right ventricular walls.^[3] Early gadolinium-enhanced sequences showed nonenhancing hypointense thrombus [Figure 3]a and [Figure 3]b, with peripheral enhancement in delayed sequences [Figure 3]c and [Figure 3]d. The subendocardial enhancement in the LV cavity is depicted in [Video 2]a and [Video 2]b. There was no late gadolinium enhancement which is suggestive of fibrosis. Bi-atrial enlargement was noted with a thickened IAS of 4 mm. There was a large LV thrombus (approximately 17 mm) layered at the LV base causing functional mitral stenosis with no mitral insufficiency. All these features would be consistent with hypereosinophilic endocarditis presenting as restrictive cardiomyopathy [Figure 2]c and [Figure 2]d.

Figure 2: Early gadolinium enhanced sequences (a and b) shows non enhancing hypointense thrombus in A and B, with peripheral enhancement in delayed sequences (c and d). Also depicted are the subendocardial enhancement in the LV Cavity. Imaging features, lab investigations and the clinical profile pointed towards Lofflers endocarditis in RA patients

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Figure 3: Cardiac magnetic resonance imaging (a) Shows thickening of the basal anterolateral, inferior, and inferior septal myocardium with a compromise of the left ventricle ( *in a and b). (c) The thickening was noted to cause narrowing of the mitral valve orifice (thick black arrow in b). There was hyperintensity suggesting myocardial inflammation in the basal anterior and anterior septal region of the left ventricle (long white arrow). (d) Perfusion images with hypoenhancing thrombus in the left ventricle cavity (short white arrow)

Click here to view

[Additional file 3]

Video 2: The video legends are the same. they depict the same finding in 2 different modalities and so are very important.

The gold standard for diagnosis in restrictive cardiomyopathy would be endomyocardial biopsy which could not be done due to logistic constraints.

Treatment and Follow-Up

Furosemide, an angiotensin-converting enzyme inhibitor, and a cardioselective beta-blocker were added in view of heart failure. Antiplatelet, statin, and anticoagulation were started. She was on parenteral steroids for rheumatoid arthritis. No other medication was added specifically for hypereosinophilia. At discharge, her symptoms improved to NYHA class I. She was readmitted with heart failure 6 months after workup when her medications were optimized further, and she was discharged. She is on regular follow-up and is presently in NYHA class I.

Discussion

We report here a patient who had presented with features of restrictive cardiomyopathy with heart failure. Although hypereosinophilia and extensive LV thrombosis were sufficient clues pointing toward Loeffler's endocarditis, the imaging features to differentiate the underlying pathologies are discussed here.

Hypertrophic cardiomyopathy may present as heart failure with preserved ejection fraction. The cardinal findings are of cardiac hypertrophy causing LV diastolic dysfunction. Myocyte hypertrophy and disarray are associated with fibrosis which is evident on late gadolinium CMR. In addition, mitral valve abnormalities are associated leading to mitral regurgitation. The ECG also shows evidence of LV hypertrophy.

Cardiac amyloidosis is a condition of heart failure with preserved ejection fraction where the dominant imaging finding is the appearance of cardiac “hypertrophy.” These patients often do not demonstrate LV hypertrophy on ECG. The “hypertrophy” on imaging represents amyloid fibril deposition rather than myocyte hypertrophy/hyperplasia, which explains why ECG voltages are decreased rather than increased. The degree of hypertrophy/voltage reduction is variable in each patient. In a patient without classic imaging findings, it is important to maintain clinical suspicion in the appropriate circumstances (e.g., unexplained heart failure in a patient with myeloma or unexplained heart failure in a patient with proteinuria/macroglossia).

Cardiac amyloidosis causes abnormal patterns of late gadolinium enhancement on CMR in both global transmural and subendocardial distribution.^[4],[5] Elevations in myocardial spin-lattice relaxation times on CMR are frequently encountered as well.^[6] Strain echocardiography typically reveals basal >apical-predominant impairments in strain.^[7] Although the degree of CMR and strain abnormalities has been correlated with patient outcomes, to date, it is difficult to confidently know that they add incremental information over other prognostic grading systems.^[8] In addition, the patterns are not specific enough for diagnosing amyloidosis. Therefore, one cannot obviate the need for biopsy-proven diagnosis.

Loeffler's endocarditis can cause heart failure with preserved ejection fraction. Patients usually present with a short duration of history of cough and fever, sinus tachycardia, intense hypereosinophilia, and layered thrombus in the LV. CMR demonstrates certain classical findings such as diffuse global endocardial hypoperfusion on first-pass contrast-enhanced perfusion, diffuse subendocardial delayed enhancement, and thrombus formation. The subendocardial delayed enhancement is caused by fibrosis of the endocardium due to stacking of eosinophils. The fibrosis results in restrictive cardiomyopathy with impaired LV diastolic function. Apical/basal thrombus formation occurs due to intense endocardial inflammation and subsequent necrosis.^[9]

In our patient, there was no LV hypertrophy on ECG. 2D echocardiography demonstrated thickening of the LV basal segments and free wall which was caused by a layered thrombus. The IVS was spared. The layered thrombus in the basal LV caused restriction of the mitral annulus and basal portions of the leaflets causing functional mitral stenosis. There was preserved LV ejection fraction. CMR revealed normal LV wall thickness with restricted diastolic expansion. STIR myocardial hyperintensity was noted in the anteroseptal and septal areas in the basal and mid-cavity segments. Postcontrast sequences showed diffuse subendocardial enhancement of the atrial wall, IAS, LV wall, and RV walls.^[3] There was no late gadolinium enhancement which is suggestive of fibrosis. A large LV thrombus was noted at the basal and posterior regions of the LV, causing restriction of mitral leaflets and functional mitral stenosis.

Given that there was no endocardial biopsy to prove Loeffler's endocarditis, a strong clinical suspicion, intense hypereosinophilia, and imaging studies (2D echocardiography and CMR) demonstrating features consistent with this diagnosis, we concluded that this patient had presented with Loeffler's endocarditis. The early diagnosis of this condition is imperative as early treatment can reverse this condition with a favorable prognosis.

Conclusion

A strong clinical suspicion of hypereosinophilic endocarditis was present in this patient due to the intense eosinophilia, presence of LV thrombus, and preserved LVEF. The additional clues in the imaging studies detailed in this report help differentiate the different forms of restrictive cardiomyopathy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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