A 42-year-old man initially presented with eyelid ptosis and was subsequently diagnosed with myasthenia gravis based on a positive edrophonium test. Chest computed tomography revealed an anterior mediastinal mass consistent with thymoma.

The patient underwent extended thymectomy via median sternotomy for the treatment of myasthenia gravis and thymoma. Complete resection was not achievable because the tumor was firmly adherent to the aorta; therefore, partial tumor biopsy with lymph node sampling was performed. Histopathological examination confirmed an invasive thymoma, Masaoka stage III, without lymph node metastasis. Postoperatively, residual disease was treated with thoracic radiotherapy to the anterior mediastinum, using 10-MV X-rays with anterior oblique opposed fields, to a total dose of 60 Gy in 30 fractions, in combination with two cycles of chemotherapy consisting of cyclophosphamide, vincristine, and prednisolone. This initial course of radiotherapy was limited to the mediastinum and did not involve cardiac exposure. Following the initial course of radiotherapy, the patient developed radiation pneumonitis, which improved with intensification of corticosteroid therapy.

Several years later, long-term corticosteroid therapy for myasthenia gravis resulted in osteonecrosis of the femoral head, necessitating left total hip arthroplasty. Subsequently, worsening myasthenic symptoms required hospitalization, and additional immunosuppressive therapy with tacrolimus was initiated alongside prednisolone and pyridostigmine.

Later in the disease course, the patient developed progressive dyspnea, generalized fatigue, and fever. Imaging studies revealed pleural and pericardial effusions, and contrast-enhanced computed tomography demonstrated a 60-mm enhancing mass infiltrating the lateral wall of the left ventricle with pericardial involvement, findings consistent with recurrent malignant thymoma (Fig. 1). Pericardial and pleural drainage were performed, followed by pleurodesis. Subsequent video-assisted thoracoscopic biopsy and pericardial fenestration confirmed recurrent thymoma with pericardial and myocardial invasion. At the age of 52, salvage thoracic radiotherapy was administered to the recurrent lesion using 10-MV X-rays with an anteroposterior–posteroanterior opposing-field technique, delivering a total dose of 60 Gy in 30 fractions (Fig. 2a), which resulted in complete radiologic remission. In contrast to the initial treatment course, this second course of radiotherapy involved direct cardiac exposure due to pericardial and myocardial invasion.

Fig. 1The alternative text for this image may have been generated using AI.

Contrast-enhanced CT of recurrent thymoma with myocardial invasion. Contrast-enhanced computed tomography shows a recurrent thymoma infiltrating the lateral wall of the left ventricle with pericardial involvement. A well-enhancing mass measuring approximately 60 mm is observed

Fig. 2The alternative text for this image may have been generated using AI.

Spatial correlation between radiation dose distribution and myocardial metabolic abnormality. (a) Dose distribution of the second course of thoracic radiotherapy, demonstrating the high-dose region involving the anterior to lateral wall of the left ventricle. (b) ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography revealing focal increased glucose uptake in the corresponding myocardial region

The patient remained clinically stable for an extended period thereafter. At a follow-up visit, he was evaluated by the cardiology department for palpitations; however, no significant cardiac abnormalities were identified, and he was managed with observation alone.

After a long asymptomatic period, at the age of 67, approximately 15 years after the second course of thoracic radiotherapy, the patient developed exertional dyspnea and anorexia. He was initially treated at another institution for presumed pneumonia; however, his symptoms progressively worsened, and bilateral lower-extremity edema subsequently developed. Positron emission tomography demonstrated no evidence of recurrent thymoma, and he was admitted to our institution for further evaluation.

The patient had no history of diabetes mellitus, chronic kidney disease, hypertension, or dyslipidemia. He had a smoking history of approximately 20 cigarettes per day from 16 to 53 years of age.

Cardiac magnetic resonance imaging was not performed. Transthoracic echocardiography revealed right atrial enlargement and inferior vena cava dilation, with reduced left ventricular systolic function (left ventricular ejection fraction, 41%). Moderate mitral regurgitation with mitral valve prolapse was also noted. Laboratory investigations revealed an elevated B-type natriuretic peptide level. To exclude ischemic heart disease, coronary angiography was performed, which revealed no significant stenosis in the major coronary arteries.

Subsequent myocardial scintigraphy was conducted to assess myocardial metabolism and perfusion. Dual-isotope ⁹⁹ᵐTc/¹²³I imaging was acquired using a dedicated cardiac cadmium-zinc-telluride single-photon emission computed tomography system without computed tomography, precluding computed tomography-based attenuation correction. BMIPP single-photon emission computed tomography showed a well-demarcated reduction in tracer uptake in the anterior to lateral wall of the left ventricle (Fig. 3a and c), whereas MIBI scintigraphy demonstrated preserved perfusion in the corresponding region (Fig. 3d and f). The area of metabolic–perfusion mismatch precisely corresponded to the previous high-dose radiation field involving the heart. Fluorodeoxyglucose positron emission tomography, performed to evaluate for thymoma recurrence, demonstrated no abnormal uptake indicative of recurrent malignancy. However, focal increased FDG uptake was noted in the anterior to lateral wall of the left ventricle (Fig. 2b). Retrospective dose–volume analysis revealed a mean heart dose of 12.8 Gy during the second course of radiotherapy, with the anterior left ventricular wall receiving a maximum dose of 61.7 Gy.

Fig. 3The alternative text for this image may have been generated using AI.

Dual myocardial scintigraphy demonstrating metabolic–perfusion mismatch. (a) ¹²³I-β-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) in the axial view demonstrates a well-demarcated reduction in tracer uptake in the anterior to lateral wall of the left ventricle. (b) ¹²³I-BMIPP SPECT in the coronal view shows concordant reduction in tracer uptake in the anterior to lateral left ventricular wall. (c) ¹²³I-BMIPP SPECT polar map (bull’s-eye plot) demonstrates a regional reduction in tracer uptake in the corresponding anterior to lateral left ventricular segments. (d) Corresponding axial ⁹⁹ᵐTc-methoxyisobutylisonitrile (MIBI) SPECT demonstrates preserved myocardial perfusion in the same region. (e) Corresponding coronal ⁹⁹ᵐTc-MIBI SPECT demonstrates preserved perfusion in the corresponding region. (f) ⁹⁹ᵐTc-MIBI SPECT polar map (bull’s-eye plot) demonstrates preserved perfusion in the same segments, facilitating objective visualization of the metabolic–perfusion mismatch and its regional extent. Note: As computed tomography-based attenuation correction was not available, mild inferior–posterior reduction on ⁹⁹ᵐTc-MIBI may reflect attenuation

Based on these imaging findings and the long-term clinical course, a diagnosis of non-ischemic heart failure secondary to radiation-induced myocardial metabolic impairment was established. Standard medical therapy for heart failure resulted in symptomatic improvement, and the patient was discharged with planned outpatient follow-up.