Rapid regression of marked left ventricular septal hypertrophy following immunosuppressive therapy in cardiac sarcoidosis

Abstract

A 46-year-old man presented with asymmetric remarkable left ventricular (LV) septal hypertrophy (maximal wall thickness: 24 mm) and complete atrio-ventricular block. Systemic sarcoidosis with a cardiac lesion was diagnosed by a supraclavicular lymph node biopsy. Following pacemaker implantation, the patient received immunosuppressive therapy with corticosteroids and methotrexate. One week after starting treatment, echocardiography and cardiac magnetic resonance (CMR) imaging showed reduced LV septal hypertrophy. At the 6-month follow-up, further thinning of the basal septal wall and enlargement of the LV with a decreased ejection fraction were observed, despite resolution of abnormal uptake in ¹⁸F-fluorodeoxyglucose positron emission tomography. A reduction in T2 values on CMR indicated that the initial hypertrophy was associated with edematous and inflammatory changes. Our findings suggest that there were heterogeneous lesions in the myocardium, such as edematous lesions responsive to immunosuppressive therapy and fibrotic lesions progressing to LV wall thinning.

Learning objective

Cardiac sarcoidosis with asymmetrical and remarkable hypertrophy is rare in the clinical setting, and using multimodality imaging in addition to histological findings is necessary for diagnosing this condition. Multimodality imaging including echocardiography and cardiac magnetic resonance are useful for evaluating myocardial characterization and confirming remarkable changes in left ventricular wall thickness and dysfunction after immunosuppression therapy.

Introduction

Sarcoidosis is a systemic inflammatory disease, and its causes are not well understood. Cardiac sarcoidosis is fatal through the occurrence of arrhythmias and/or heart failure with reduced left ventricular (LV) ejection fraction [1]. Therefore, early diagnosis and start of treatment are required in the clinical settings [2]. In the diagnosis of cardiac sarcoidosis, LV wall thinning, especially in basal septum lesion, and local asynergy incompatible with coronary perfusion area are common morphologies, and a hypertrophic change in LV wall is rare [3]. We present the case of a relatively young male with marked LV septal hypertrophy who had a difficulty of differential diagnoses and showed remarkable change in the wall thickness after treatment.

Case report

A 46-year-old man who had no previous medical history was referred to our hospital for the diagnosis of a complete atrioventricular block. In his physical examination, his blood pressure was 135/57 mmHg, and his heart rate was 50 beats/min. No significant murmur was audible, and the supraclavicular lymph nodes were palpable. Laboratory data on admission showed a slightly increased serum interleukin-2 receptor (638 U/mL) and B-type natriuretic peptide (45.1 pg/mL) concentrations, but the angiotensin-converting enzyme concentration was in the normal range (14.9 U/L). Transthoracic echocardiography showed severe hypertrophy (maximum wall thickness: 24 mm) at the mid to basal septal and inferior regions, despite a normal LV ejection fraction (61 %) (Fig. 1A). Contrast-enhanced cardiac magnetic resonance (CMR) imaging demonstrated 1) strong late gadolinium enhancement (LGE), and 2) hyperintensity in black-blood T2-weighted imaging (Fig. 1B) and prolonged T2 values (64.0 ms) in T2 mapping. ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography (¹⁸F-FDG PET-CT) showed abnormal uptake of ¹⁸F-FDG in the hypertrophic region and bilateral supraclavicular and hilar lymph nodes (Fig. 1C). Differential diagnoses in patients with asymmetric remarkable hypertrophy include hypertrophic cardiomyopathy, Fabry disease, malignant lymphoma, and cardiac sarcoidosis. A biopsy from the supraclavicular lymph node identified noncaseating epithelioid granuloma. Therefore, the patient was diagnosed with systemic sarcoidosis, including cardiac lesions, although noncaseating epithelioid granuloma was not observed from a cardiac biopsy. After a pacemaker was implanted for a complete atrioventricular block, immunosuppressive therapy was started with a corticosteroid (20 mg/day) and methotrexate (6 mg/week). In follow-up echocardiography and CMR imaging performed 1 week after the treatment, the thickness of the septal to the inferior wall had already decreased (maximum: from 24 to 18 mm on echocardiography). Additionally, the T2 value on CMR was shortened to 42.8 ms, while there was no change in the distribution of LGE (Fig. 2, Fig. 3). At 6 months after starting treatment (corticosteroid: 15 mg/day and methotrexate: 6 mg/week), ¹⁸F-FDG PET-CT showed no uptake of ¹⁸F-FDG in the heart or lymph nodes, which indicated that the immune suppressive therapy was effective (Fig. 3). However, the atrioventricular block had not improved (ventricular pacing rate was almost 100 %), and the ejection fraction was decreased to 33 % with dyskinesis and progressive thinning of the previously thickened wall (from 24 to 6 mm), showing LGE on CMR.

Fig. 1.

Multimodality images on admission. Transthoracic echocardiography in the parasternal long axis (A-1) and short axis (A-2) views show marked left ventricular hypertrophy in the mid to basal septal region (yellow arrow). Contrast-enhanced cardiac magnetic resonance imaging shows late gadolinium enhancement at the delayed enhance phase (10 min) (B-1), and black-blood T2-weighted imaging (B-2) showed a high-intensity signal in the hypertrophic lesion (red arrow). ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography shows considerable uptake in the bilateral supraclavicular (C-1) and hypertrophic regions in the myocardium (white arrow) (C-2).

Fig. 2.

Transthoracic echocardiography of changes in hypertrophic regions after treatment. In the parasternal long-axis (upper row) and short-axis (lower row) views, the septal and inferior regions show severe hypertrophy at baseline (A) (red arrow). One week after treatment, the septal wall thickness has improved (maximum: from 24 to 18 mm: white arrow), and progressive thinning (6 mm) of a previously thickened wall can be seen (yellow arrow) at 6 months after treatment.

Fig. 3.

Contrast-enhanced cardiac magnetic resonance (CMR) imaging and ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography (¹⁸F-FDG PET-CT) of changes in hypertrophic regions after treatment. Late gadolinium enhancement (LGE) at the delayed enhanced phase (10 min) (upper row) and black-blood T2-weighted imaging (middle row) and ¹⁸F-FDG PET-CT (lower row) at baseline (A), 1 week after treatment (B), and 6 months after treatment (C). In the CMR imaging, the T2 value was shortened from 64.0 to 42.8 ms (red arrow), although LGE distribution was not changed even at 6 months after treatment (yellow arrow). The ¹⁸F-FDG PET-CT imaging showed abnormal uptake of FDG in hypertrophic regions in the myocardium before treatment (white arrow), but no uptake was demonstrated in the myocardium 6 months after treatment.

N.A., not available.

Discussion

Our case showed a drastic change in the wall thickness, ejection fraction, and myocardial properties during 6 months after starting immune suppression therapy for cardiac sarcoidosis. Moreover, it could be followed with high-quality multimodality imaging such as echocardiography, CMR, and ¹⁸F-FDG PET-CT. Our search of PubMed revealed 7 cases of cardiac sarcoidosis showing LV hypertrophy and 11 cases showing LV mass (Table 1) [[4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21]]. Most patients showed a complete atrioventricular ventricular block as a cardiac manifestation and were evaluated using echocardiography, CMR, and nuclear medicine imaging. Moreover, the resolution of LV hypertrophy and mass after starting immunosuppression therapy was reported in some cases. However, the present case is rare because rapid regression of hypertrophy and then thinning of the ventricular wall and progression of LV dysfunction were observed using high-quality multimodality imaging shortly after starting immunosuppressive therapy, despite effective treatment for cardiac sarcoidosis.

Table 1.

A literature review of ‘cardiac sarcoidosis’ and ‘mass or hypertrophy’ in PubMed.

Author	Age	Sex	Morphology	Cardiac manifestations	Advanced imaging	CMR findings	Therapy	Outcome
<Hypertrophy>
Nureki SI et al., 2014 [4]	64	F	33 mm, IVS hypertrophy	Not abnormal findings	CMR Gallium scintigraphy	High-intensity signal in T2-weighted imaging	PSL30 mg per day	Improved IVS thickening and completely diminished
Barral M et al., 2015 [5]	51	M	25 mm, IVS hypertrophy	Sustained VT, first-degree AVB	CMR	High-intensity signal inT2-weighted imaging	Ablation of VT Oral steroid and intravenous cyclophosphamide	Disappearance of ventricular tachycardia and partial conduction recovery with first-degree AV block. Decreased the IVS thickness
Yazaki Y et al., 1998 [6]	62	F	18 mm, basal IVS hypertrophy	First-degree AVB with CRBBB and left anterior fascicular brock	Gallium scintigraphy		PSL 60 mg per day	Decreased wall thickening Improved AV conduction
Mathias IS et al., 2021 [7]	64	F	17 mm, IVS hypertrophy	Left ventricular tract obstruction	CMR 18F-FDG-PET	LGE (+)	PSL and Methotrexate	Not mentioned
Radulescu B et al., 2010 [8]	37	M	16 mm, IVS hypertrophy and 13.8 mm, posterior wall hypertrophy.	Non sustained VT	CMR 18F-FDG-PET	Perfusion defects and LGE (+)	Steroid	Rapid regression (6 days) of left ventricular hypertrophy (interventricular septum 10.7 mm, posterior wall 11.1 mm)
Okamura H et al., 2005 [9]	42	M	13 mm, right ventricular wall hypertrophy	Advanced AVB	CT		PSL40 mg per day	Disappeared hypertrophy of right ventricular wall
Umetani K et al., 2000 [10]	65	M	13 mm, IVS hypertrophy	Complete AV block	Gallium scintigraphy		PSL 30 mg per day	Disappeared abnormal uptake of Gallium
<Mass>
Joffe ll et al., 1995 [11]	29	F	RA and LV lateral wall, Pericardial space mass	VT	None		PSL 60 mg per day	Reduction of mass size
Scatarige JC et al., 2000 [12]	33	F	Mass in the IVS	VT	CMR	Not mentioned	Not mentioned	Not mentioned
Abrishami B et al.,2004 [13]	45	M	LA arising from the interatrial septum	Complete AVB	Gallium scintigraphy		Surgical resection	Not mentioned
Uchida M et al., 2012 [14]	39	M	Mass echo in basal IVS	Complete AVB	CMR Gallium scintigraphy			Reduction of mass size. Improvement of abnormal uptake of Gallium in the myocardium.
Betric M et al., 2016 [15]	33	M	Right ventricular mass	Complete AVB	CMR 18F-FDG-PET	Not mentioned	Not mentioned	Not mentioned
Takahashi Y et al., 2016 [16]	40	F	Mass echo in the RA (12 × 12 mm)	Compete AVB	CMR 18F-FDG-PET	Transmural LGE (+), High intensity signal in T2-weighted imaging	PSL40 mg per day	Reduction of RA mass
Fujimoto R et al., 2018 [17]	52	F	Mass on the RV side of IVS and thickening of the basal inferior of LV	First-degree AVB and CRBBB with intermittent third-degree AVB	CMR 18F-FDG-PET	LGE (+) High intensity signal in T2-weighted black blood image	PSL 30 mg per day	Mass size reduction. Resolution of AVB
Park I et al., 2022 [18]	20	F	Mass at the basal septum	Intermittent complete AVB	CMR 18F-FDG-PET	LGE, high intensity signal in T2-weighted imaging	PSL 30 mg per day	Improved atrioventricular conduction and regression of septal mass
Hutt E et al., 2024 [19]	26	M	LV mass (Lateral wall and the anterolateral papillary muscle)	Non sustained VT	CMR 18F-FDG-PET	LGE(+) Isointensity signal on T1-weighted sequence and hyperintense signal on T2 STIR.	subcutaneous implantable cardioverter defibrillator implantation. Methylprednisolone 1 g/day and PSL30 mg/day	Resolution of LV mass 6 months after treatment
Newman N et al., 2024 [20]	45	F	Mass in the RA	Second-degree AVB	CMR 18F-FDG-PET	LGE(+)	Surgical resection, ICD implantation, PSL 30 mg per day	Disappeared abnormal uptake of 18F-FDG
Asakura K et al., 2022 [21]	71	F	Focal thinning of basal IVS	Complete AVB	18F-FDG-PET		PSL30mg per day	Non-abnormal uptake of 18F-FDG Size of mass had not changed

IVS, interventricular septum; RA, right atrium; LA, left atrium; LV, left ventricle; AVB, atrio-ventricular block; VT, Ventricular tachycardia; CRBBB, complete right bundle branch block; PSL, prednisolone; LGE, late gadolinium enhancement; CMR, cardiac magnetic resonance; CT, computed tomography; ¹⁸F-FDG-PET, ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography; ICD, implantable cardioverter-defibrillator.

CMR imaging was useful for assessing myocardial properties in the hypertrophic segment. Generally, CMR imaging plays a vital role in the diagnosis and prognostic prediction of cardiac sarcoidosis by evaluating the distribution and degree of LGE in addition to morphological assessment [22]. In the present case, T2-based imaging and LGE were essential for estimating changes in myocardial properties before and after immunosuppressive therapy. Prolonged T2 values in the hypertrophic segment before immunosuppressive therapy indicated remarkable edematous and inflammatory changes. The T2 value was shortened at 1 week after treatment. However, LV dysfunction progressed with thinning of the LV wall accompanied by strong LGE 6 months later. Prolonged T2 segments showing fewer LGE are considered acute-phase lesions and respond well to immunosuppressive therapy. A case with prolonged T2 segments and complete atrioventricular block was previously reported showing improvement in atrioventricular conduction after immunosuppressive therapy [23]. We found prolonged T2 values and strong LGE at the hypertrophic segment in the present case. Therefore, edematous changes and severe fibrosis of the LV wall might have been intermingled. As a result of marked improvement in the edematous changes, only a severely impaired fibrotic segment (thinning of the myocardium) remained after treatment, and dyskinetic motion of the thin region was observed in a short period. Atrio-ventricular conduction had not improved even after immunosuppressive therapy, and the patient depended on a pacemaker, which is compatible with the presence of a severely impaired fibrotic segment.

Echocardiography and CMR imaging were useful for detecting and assessing the mechanism of chronological changes.

Consent statement

Written informed consent was obtained from the patient to publish this case report, including accompanying images.

Declaration of competing interest

The authors declare that there is no conflict of interest.

Appendix A. Supplementary data

The following are the supplementary data related to this article.

Online Video 1

Transthoracic echocardiography (parasternal long-axis view) at baseline.

Oline Video 2

Transthoracic echocardiography (short-axis view at mitral valve level) at baseline.

Online Video 3

Transthoracic echocardiography (parasternal long-axis view) at 6 months after treatment.

Online Video 4

Transthoracic echocardiography (short-axis view at mitral valve level) at 6 months after treatment.