Isolated atrial myocarditis presenting with atrial arrhythmias and diffuse thickening of the atrial wall diagnosed via atrial biopsy: a case report

Abstract

Background

Isolated atrial myocarditis is rarely diagnosed in non-open-heart surgical cases. We report a case of isolated lymphocytic atrial myocarditis presenting with atrial arrhythmias, syncope, and atrial wall thickening, confirmed histologically by transcatheter atrial biopsy and multimodality imaging.

Case summary

A 69-year-old woman presented to the emergency department with general fatigue and a syncopal episode. Electrocardiogram revealed sick sinus syndrome (SSS) with a heart rate of 40 beats/min. Laboratory tests indicated a mild inflammatory response without cardiac enzyme level elevation. Transthoracic echocardiography demonstrated left atrial wall thickening and mild pericardial effusion. Contrast-enhanced computed tomography revealed a thrombus in the left atrial appendage, ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) showed diffuse uptake in both atria without ventricular involvement. Three weeks later, the patient presented with atrial fibrillation. An endomyocardial atrial biopsy was performed to histologically investigate the cause of atrial wall thickening, which revealed lymphocytic myocarditis, thereby ruling out malignant lymphoma and amyloidosis. No causative virus was identified, and immunosuppressive therapy was not initiated because the patient showed spontaneous improvement in atrial arrhythmia and atria wall thickening. Anticoagulation therapy resulted in complete resolution of the thrombus within 3 months. Follow-up FDG-PET/CT at 5 months confirmed the resolution of atrial uptake, and the patient remained symptom-free without SSS or AF recurrence at the 1-year follow-up.

Discussion

In cases of isolated atrial myocarditis presenting with atrial arrhythmias and atrial wall thickening, a combination of imaging modalities and histological evaluation by atrial biopsy may be helpful in establishing a definitive diagnosis.

Learning points.

• Isolated atrial myocarditis can present with atrial arrhythmias, including sick sinus syndrome and atrial fibrillation, and should be considered in cases of unexplained atrial wall thickening.

• Imaging modalities, such as FDG-PET/CT, should be initially performed, and if necessary, histological evaluation by atrial biopsy may be performed to aid in establishing the diagnosis.

Introduction

Isolated atrial myocarditis is a rare cardiac condition. Most histologically confirmed cases have been identified as giant cell myocarditis, with the majority having been incidentally detected during open-heart surgery or at autopsy.^1,2 Here, we report a rare case of isolated lymphocytic atrial myocarditis presenting with sick sinus syndrome (SSS), atrial fibrillation (AF), and atrial wall thickening, which was histologically diagnosed by atrial biopsy and multimodality imaging.

Summary figure

Case presentation

A 69-year-old woman with an unremarkable medical history presented to the emergency department of one of the authors’ institutions with general fatigue and a syncopal episode. On physical examination, her vital signs were as follows: body temperature, 36.3°C; heart rate, 40 beats/min and regular; blood pressure, 139/84 mmHg; respiratory rate, 22 breaths/min; and oxygen saturation, 97% on room air. Cardiac and pulmonary auscultation was unremarkable, with no evidence of lower-limb oedema. Electrocardiography revealed SSS with a heart rate of 40 beats/min (Figure 1A), which was considered the cause of her syncope.

Figure 1.

Electrocardiogram. (A) ECG at the first visit revealed a sick sinus syndrome without significant ST-T changes (heart rate, 40 bpm; QRS duration, 84 ms). (B) Atrial fibrillation at the 3-week follow-up visit (heart rate, 71 bpm; QRS duration, 78 ms). ECG, electrocardiogram.

The laboratory examination findings were as follows: white blood cell count, 8800/μL (reference: 4000–10 000/μL); C-reactive protein level, 1.11 mg/dL (reference: <0.3 mg/dL); normal renal function, electrolyte, and Troponin T levels; and brain natriuretic peptide level, 338 pg/mL (reference: <35 pg/mL). Chest radiography revealed bilateral hilar congestion, consistent with congestive heart failure. Transthoracic echocardiography demonstrated diffuse thickening of the left atrial (LA) wall (∼5 mm) and mild circumferential pericardial effusion, with preserved left ventricular wall thickness (7 mm), normal motion, and no considerable valvular disease (Figure 2A–C). Contrast-enhanced computed tomography (CT) revealed diffuse thickening of both atrial walls and a thrombus in the LA appendage (Figure 2D and E). Diuretics (azosemide, 30 mg/day) were initiated for heart failure, and anticoagulant therapy with apixaban (10 mg/day) was started for the thrombus in the LA appendage. Given the patient’s stable condition without prolonged pauses on the electrocardiogram and her preference for outpatient management, pacemaker implantation was not pursued.

Figure 2.

Baseline imaging studies. (A–C) Transthoracic echocardiography showing circumferential thickening of the left atrial wall (∼5 mm, arrowheads). The left ventricular wall thickness was 7 mm, and the left ventricular ejection fraction was 65% without wall motion abnormalities. (D, E) Contrast-enhanced computed tomography showing similar thickening of the atrial septum and left atrial wall (arrowheads), with a thrombus noted in the left atrial appendage (arrow). (F, G) ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) showing marked uptake in both atrial walls without ventricular involvement.

The initial differential diagnoses included malignant lymphoma,³ cardiac sarcoidosis,⁴ and atrial amyloidosis.^{5  18}F-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) was performed to evaluate for the presence of systemic disease, particularly malignant lymphoma after a 12 h fast following a low-carbohydrate diet. The scan showed diffuse ¹⁸F-FDG uptake in both atria without ventricular involvement (Figure 2F and G), as well as mild uptake in the tonsil. A biopsy of the tonsil revealed no pathological abnormalities. Given that there was insufficient evidence of ventricular myocarditis or other forms of ventricular cardiomyopathy on echocardiography and FDG-PET/CT, cardiac magnetic resonance imaging (MRI) was not performed. Three weeks later, the patient presented with AF at a follow-up visit (Figure 1B). Rhythm control was not immediately pursued owing to the presence of a thrombus in the LA appendage. Based on her symptoms and follow-up ECG findings, AF persisted for ∼1 month before spontaneously converting to a sinus rhythm.

Two months later, after confirming the resolution of the thrombus in the LA appendage, the patient was referred to our institution for atrial biopsy, given our expertise on this procedure.⁶ As FDG-PET/CT had revealed a high uptake in both atria, the right atrial (RA) septum was targeted, and five specimens were obtained from the limbus of the fossa ovalis under fluoroscopic and transoesophageal echocardiographic (TEE) guidance (Figure 3A–D).

Figure 3.

Transcatheter atrial biopsy under fluoroscopic and TEE guidance. (A) Fluoroscopy. (B) TEE (mid-oesophageal bicaval view, 110°). (C) TEE (mid-oesophageal bicaval view, 20°). Arrows indicate the tip of the biopsy catheter. (D) Macroscopic findings of the transcatheter biopsy specimen. LA, left atrium; RA, right atrium; TEE, transoesophageal echocardiography.

Histopathological examination revealed partial replacement of the myocardium with loose collagen fibres with infiltration of numerous small lymphocytes and plasma cells (Figure 4A–C). Congo red staining was negative for amyloid deposits (Figure 4D). Immunohistochemical analysis showed a mixture of CD3-positive T and CD20/CD79a-positive B lymphocytes, with no atypical lymphocytes, thereby ruling out malignant lymphoma (Figure 4E–H). Based on these findings, the patient was diagnosed with isolated atrial lymphocytic myocarditis.

Figure 4.

Histopathological analysis. H&E staining at (A) low and (B) high magnifications. (C) Masson’s trichrome staining. (D) Congo red staining. Immunostaining for (E) CD3, (F) CD20, (G) CD79a, and (H) Ki67. H&E, haematoxylin–eosin.

A multivirus detection assay using quantitative polymerase chain reaction (PCR; multiplex TaqMan real-time PCR) was performed using nucleic acids extracted from formalin-fixed, paraffin-embedded atrial biopsy specimens, as previously described.⁷ No viral genomes, including enteroviruses, adenoviruses, parvovirus B19, and several herpesviruses, as well as influenza and coronaviruses, were detected.

As atrial arrhythmia resolved spontaneously and the atrial wall thickening improved on echocardiography (3 mm) and CT (Figure 5A and B) at the time of histological diagnosis, immunosuppressive therapy was not performed. Five months later, follow-up FDG-PET/CT showed a resolution of the atrial uptake (Figure 5C). A year after onset, the patient remained free from SSS and AF, diuretics were discontinued, and anticoagulant therapy was maintained. No antiarrhythmic drug administration, catheter ablation, or pacemaker implantation was performed.

Figure 5.

Imaging studies in the chronic phase. (A, B) Transthoracic echocardiography and contrast-enhanced computed tomography performed at 2 months after symptom onset showed improvement of the atrial wall thickening and resolution of the thrombus in the left atrial appendage. (C) ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) demonstrated resolution of the atrial uptake.

Discussion

The present report describes a rare case of isolated lymphocytic atrial myocarditis presenting with atrial arrhythmia and atrial wall thickening, which was histologically diagnosed by transcatheter atrial biopsy.

In Lim et al.’s literature review, 18 cases of isolated atrial myocarditis were reported between 1964 and 2021.² Among the 15 histologically confirmed cases, 14 were giant-cell atrial myocarditis and 1 was lymphocytic myocarditis. Eleven cases were diagnosed using atrial samples obtained during cardiac surgery and two were diagnosed post-mortem, with most of them being incidental findings. Contrarily, two cases of giant-cell atrial myocarditis were diagnosed by transcatheter biopsy,^8,9 with one case developing after catheter ablation for AF. AF was present in 12 cases and SSS in 1. Immunosuppressive therapy, mainly prednisolone, was administered in four cases, and anticoagulation was used in eight cases. Similar to our case, the overall prognosis of the reported cases was generally favourable, with 15 out of the 18 patients surviving for 2 months to 6 years, suggesting that the outcome of isolated atrial myocarditis may have a better outcome compared to ventricular myocarditis.^10,11

The diagnostic process is challenging because cases presenting with atrial wall thickening are rare. Moreover, differential diagnoses such as malignant lymphoma,³ cardiac sarcoidosis,⁴ and atrial amyloidosis⁵ needed to be excluded, as imaging modalities, such as FDG-PET/CT alone, cannot provide a definitive diagnosis. Although cardiac MRI can detect atrial wall thickening and oedema,^1,9 further evaluation with late gadolinium enhancement or T1 mapping remains challenging owing to the limited spatial resolution of the thin atrial wall and the lack of standardized imaging protocols. Furthermore, atrial biopsy has been considered technically challenging owing to its potential procedural risk, and surgical biopsy may also need to be considered as an alternative approach.

The feasibility of RA septal biopsy has been demonstrated in previous reports,^12,13 and its safety was further confirmed in our series of 1000 cases using intracardiac echocardiography or TEE, with 996 successful biopsies and no complications.⁶ Although LA septal biopsy is possible,⁸ it requires transseptal access and carries potential risks of tissue loss and embolization. In the present case, given the atrial septal wall thickening observed on CT and ¹⁸F-FDG uptake on PET/CT, RA septal biopsy was selected.

In isolated atrial myocarditis, marked lymphocytic infiltration, cardiomyocyte necrosis, and replacement fibrosis are evident, as observed in the present case. Contrarily, AF-related remodelling typically shows an expansion of the intercellular spaces, interstitial fibrosis, myofibrillar loss, reduced cardiomyocyte nuclear density, and amyloid deposition.^6,14 None of our 996 biopsy cases met the Dallas criteria for myocardidis.¹⁵ These findings suggest that atrial myocarditis represents an active inflammatory process distinct from chronic AF-related structural remodelling.

Conclusion

In our rare case of isolated atrial myocarditis presenting with atrial arrhythmia and atrial wall thickening, diagnosis and differentiation from other diseases associated with atrial wall thickening were challenging. However, multimodality imaging combined with atrial biopsy enabled a definitive diagnosis of isolated atrial lymphocytic myocarditis.

Lead author biography

I was born and raised in Saga, Japan. After graduating from the Faculty of Medicine at Saga University in 2020, I completed a 2-year residency at Saga University Hospital. I then served as a cardiology fellow at Saga Prefectural Medical Center Koseikan in 2022 and have been continuing my fellowship in cardiovascular medicine at Saga University Hospital since 2023. My main interests are arrhythmia management and catheter ablation, with a strong commitment to improving patient care and advancing cardiovascular research.

Author contributions

Makoto Edayoshi (Data curation, Formal analysis, Investigation, Methodology, Writing—original draft, Writing—review & editing), Kensuke Yokoi (Data curation, Formal analysis, Writing—original draft, Writing—review & editing), Takanori Yamaguchi (Conceptualization, Supervision, Writing—review & editing), Nobuhide Watanabe (Investigation, Methodology, Writing—review & editing), and Koichi Node (Supervision, Writing—review & editing).

Funding

None declared.

Data availability

The data underlying this article will be shared on reasonable request to the corresponding author.