A case of cardiac sarcoidosis mimicking acute phase of takotsubo cardiomyopathy evaluated by multimodality cardiac imaging

Abstract

The patient was a 68-year-old woman who experienced loss of consciousness owing to a seizure while walking and bruised her face. Twelve‑lead electrocardiography displayed a complete atrioventricular block. Transthoracic echocardiography displayed hypokinesis from the middle to apex of the myocardium. Emergency coronary angiography displayed no clear stenosis of the coronary arteries, and left ventriculography displayed takotsubo-like abnormal left ventricular wall motion. ^99mTc-sestamibi/¹²³I-beta-methyl iodophenyl pentadecanoic acid dual single-photon emission computed tomography displayed a perfusion/metabolism mismatch in the left apex, anterior segment, and inferior segment of the myocardium in the acute phase, which improved in the chronic phase. Similar mismatch findings were observed in the ventricular septum, which persisted in the chronic phase. Blood biomarkers of sarcoidosis were positive. Myocardial delayed enhancement was observed in the mid layer of the basal septum and inferior wall on cardiac magnetic resonance imaging. Fluorodeoxyglucose-positron emission tomography displayed signal accumulation in the basal septum. The clinical course of the patient suggested the possibility of cardiac sarcoidosis combined with takotsubo cardiomyopathy. This is a valuable case in which changes over time were detected by multimodality cardiac imaging.

Learning objective

Cardiac manifestations of both takotsubo cardiomyopathy and sarcoidosis are similar, with both causing abnormal left ventricular wall motion. The co-occurrence of these conditions has been seldomly reported to date. The similarity of the characteristics of each condition poses a challenge in the diagnostic process. The utilization of multimodality cardiac imaging techniques, as demonstrated in the present case, is an effective means of establishing a diagnosis.

Introduction

Takotsubo cardiomyopathy causes extensive wall motion loss of the myocardium mainly in the left ventricular apex, which does not coincide with coronary artery innervation, and is induced by mental and physical stress [1]. The pathogenesis of this disease is known to include myocardial damage caused by endogenous catecholamines, microcirculatory failure, and neurogenic stunned myocardium, but the main mechanism remains unclear [2]. Atrioventricular block has been reported to occur in patients with takotsubo cardiomyopathy, and it often persists and may relapse in the chronic phase [3].

Sarcoidosis is a systemic granulomatous disease of unknown cause. It causes fibrosis of the myocardium, which leads to cardiac dysfunction, and involves arrhythmic complications of fatal tachycardia and bradycardia [4].

Because the characteristics of takotsubo cardiomyopathy and sarcoidosis are partially similar, it is difficult to differentiate between the two diseases when they occur together, and such cases have been rarely described previously.

Case report

The patient was a 68-year-old Japanese woman with no medical history other than tuberculosis many years previously. In 2022, while walking, she experienced sudden loss of consciousness owing to a seizure and was brought by ambulance to our hospital. She regained consciousness naturally within a few minutes. Electrocardiography displayed right bundle branch block and complete atrioventricular block (Fig. 1A). Her physical assessment results were unremarkable, except for the presence of regular bradycardia. Chest radiography displayed scarring consistent with prior tuberculosis infection, but no signs of pulmonary congestion. Although laboratory investigations showed elevated B-type natriuretic peptide level of 1168.3 pg/mL, myocardial enzymes including high-sensitivity troponin were normal. The biomarkers for sarcoidosis were high, angiotensin-converting enzyme of 31.9 IU/L, lysozyme of 19.4 μg/m, and soluble interleukin-2 receptor of 1314.0 U/m. Transthoracic echocardiography displayed a dilated left ventricle (LV), and severely reduced LV systolic function with apical ballooning. Urgent coronary angiography showed no significant coronary artery stenosis. Left ventriculography displayed abnormalities resembling takotsubo cardiomyopathy, i.e. good wall motion in the basal region but reduced motion in other areas (Fig. 1B, C). The patient was admitted to our hospital after temporary pacemaker insertion. As complete atrioventricular block persisted, and there was obstruction of the superior vena cava owing to history of pulmonary tuberculosis, we implanted a leadless pacemaker. Since both positive findings of sarcoidosis and takotsubo cardiomyopathy were observed, we planned to proceed with detailed examination.

Fig. 1.

The initial electrocardiography indicated complete atrioventricular block accompanied by right bundle branch block, and a bradycardic heart rate of 36 beats per minute (A). End diastolic phase left ventriculogram (B) and end systolic phase left ventriculogram (C). The extensive area around the mid to apical portion shows akinesis (dots), and the basal portions display hypercontraction in the end systolic phase (arrows).

Diagnosis and management

At first, ^99mTc-sestamibi/¹²³I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) dual single-photon emission computed tomography (SPECT) was performed. A perfusion/metabolism mismatch in the LV apex, inferior wall, and ventricular septum was observed, in which the size of the metabolic abnormality was larger than that of the perfusion abnormality (Fig. 2A). Although cardiac magnetic resonance imaging (MRI) displayed late gadolinium enhancement in the basal interventricular septum (IVS) and in the middle layer of the basal inferior LV wall, there were no findings of high signal on T2-weighted images signifying myocardial edema as an acute phase in takotsubo cardiomyopathy. Abnormal accumulation of ⁶⁷Ga-citrate was not observed. Fluorodeoxyglucose-positron emission tomography (FDG-PET) displayed extensive hyperaccumulation in the basal IVS and inferior wall (Fig. 3A, B). Tracer accumulation was observed in the spleen, muscles, iliac bones, and lymph nodes throughout the body. In the upper right lung, there was also tracer accumulation in the lesion from the previous pulmonary tuberculosis (Fig. 3C). Three months after the initial imaging, dual SPECT in the chronic phase displayed improved apical LV dual tracer uptake, but the decreased uptake in the basal and inferior IVS remained (Fig. 2B). The areas of decreased uptake on dual SPECT observed in both the acute phase and the chronic phase coincided with the areas of abnormal findings observed on FDG-PET and MRI. The previously observed takotsubo cardiomyopathy-like LV dysfunction had improved, and basal thinning of the ventricular septum was observed on echocardiography. From these results, we considered that the ventricular septal region of the myocardium was affected by sarcoidosis and the apical region by takotsubo cardiomyopathy. Skin and muscle biopsies were performed, but noncaseating epithelioid granulomas were not detected. When granulomatous uveitis was observed, the patient was diagnosed clinically as having cardiac sarcoidosis. From admission to the present, this patient has been observed with sustained complete atrioventricular block and pacemaker rhythm. ST-segment elevation and T-wave inversion were not observed during the clinical course.

Fig. 2.

Representative images of ^99mTc-sestamibi/¹²³I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) dual single-photon emission computed tomography (SPECT) in the acute phase (A), and in the chronic phase (B). In the chronic phase, dual SPECT displayed recovered uptake in the left ventricle apex, whereas decreased uptake was observed in the anterior and inferior sites of the ventricular septum.

Fig. 3.

Results of the fluorodeoxyglucose-positron emission tomography (FDG-PET) scan displaying a marked uptake increase in the basal septum and inferior wall [A (axial), B (sagittal): PET image merged with computed tomography image]. In the other organs, such as the spleen and various muscles and bones throughout the body, there was also substantial accumulation of FDG. Notably, the scans displayed an increased level of FDG in the upper right lung (C: maximum intensity projection image), likely owing to the previous occurrence of pulmonary tuberculosis. Furthermore, increased accumulation of FDG in the lymph nodes throughout the body was observed. The regions displaying reduced uptake in the chronic phase on single-photon emission computed tomography coincided with the areas displaying abnormalities on FDG-PET and cardiac magnetic resonance imaging.

Because of the presence of a complete atrioventricular block and active inflammation on FDG-PET, class I immunosuppressive therapy was indicated. Corticosteroid therapy will be started after evaluation of the patient's pulmonary tuberculosis activity.

Discussion

As noted above, the cardiac findings of takotsubo cardiomyopathy and sarcoidosis are similar in some respects, such as arrhythmia and cardiac dysfunction. It is known that takotsubo cardiomyopathy develops after a strong stress event. However, when bradyarrhythmia with loss of consciousness and trauma is present, as in the present case, it is difficult to determine whether the arrhythmia or takotsubo cardiomyopathy initially occurred. At first, ventricular septum thinning, which is a distinctive feature of sarcoidosis, was absent. The presence of balloon-like wall motion, attributable to takotsubo cardiomyopathy, potentially obscured these findings. As shown in Fig. 1A, the patient had complete atrioventricular block at presentation, but did not have negative T waves and QT prolongation characteristic findings as takotsubo cardiomyopathy. The lack of increased levels of myocardial enzymes in the patient's serum, along with the detection of distinct biomarkers of sarcoidosis, led us to consider the likelihood of sarcoidosis as a probable diagnosis. Vasospastic angina was considered negative because the coronary artery anatomy did not coincide with areas of wall motion loss on left ventriculography and mismatch on SPECT.

The presence of noncaseating granulomas on biopsy is the standard method for the diagnosis of sarcoidosis. However, endomyocardial biopsy is often not performed because of the insufficient diagnostic yield. The current American Thoracic Society guidelines recommend cardiac MRI and PET for the diagnosis of cardiac sarcoidosis [5]. However, some patients with takotsubo cardiomyopathy were reported to display delayed contrast enhancement on cardiac MRI and increased accumulation on FDG-PET, similarly to patients with sarcoidosis [6].

In patients with takotsubo cardiomyopathy, myocardial fatty acid metabolism is impaired in areas of reduced wall motion, resulting in decreased uptake of ¹²³I-BMIPP. Decreased uptake of perfusion tracers is also observed, but to a lesser extent than ¹²³I-BMIPP, so confirming the mismatch using 2 nuclides is useful for diagnosis [7]. In the chronic phase, both the recovery and mismatch findings disappear, but recovery of the fatty acid metabolism abnormality is seen later than that of the myocardial perfusion abnormality [8]. Cardiac sarcoidosis is also known to cause decreased uptake of the 2 radionuclides depending on the pathogenesis of sarcoidosis [9]. The mismatch region of the uptake of both radiotracers is likely to correspond to the region of increased accumulation by FDG-PET [10]. In the present case, from the results of the dual myocardial SPECT performed twice, the findings of the apical area mismatch in the acute phase were considered to be a result of takotsubo cardiomyopathy, and decreased uptake in the basal septum in the chronic phase was considered to be cardiac sarcoidosis. After reviewing the results of the multimodality imaging, we finally diagnosed the patient as having systemic sarcoidosis complicated by complete atrioventricular block. It was difficult to diagnose takotsubo cardiomyopathy in this case due to the absence of electrocardiographic changes and elevated myocardial deviation enzymes.

This is the first report to our knowledge of a rare case of a patient in whom sarcoidosis was diagnosed concomitantly with acute phase of takotsubo cardiomyopathy, which was clarified by comprehensive multimodality assessment of both the acute and chronic stages of disease.

Patient permission/consent statement

Written informed consent was obtained from the patient for publication of this case report, including accompanying images.

Declaration of competing interest

This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.