Arrhythmogenic Left Ventricular Mass as the Initial Presentation of Cardiac Sarcoidosis

Abstract

Cardiac tumors of the left ventricle are rare, and cardiac magnetic resonance is the preferred imaging tool for evaluation given superior tissue characterization. We present a case of a patient with arrhythmia and left ventricular mass that was ultimately diagnosed with cardiac sarcoidosis, reminding us that tissue is the issue.

Graphical abstract

History of Presentation

A 26-year-old man was transferred to our institution for further management of a newly diagnosed left ventricular (LV) mass after he presented locally with nonsustained ventricular tachycardia (NSVT) that manifested with symptoms of palpitations and shortness of breath.

Learning Objectives

• •To be able to narrow a differential diagnosis of cardiac masses using multimodality imaging.
• •To understand the value of tissue characterization with CMR.
• •To recognize that sarcoidosis can rarely present as a cardiac mass.

Past Medical History

Two months before presentation, the patient started experiencing intermittent palpitations. Local work-up revealed frequent premature ventricular contractions and 1 episode of NSVT for which he was started on verapamil for management of symptomatic premature ventricular contractions after the initial echocardiogram had shown a structurally normal heart. Before this, the patient had no past medical history.

Differential Diagnosis

The differential diagnosis in this young patient with LV mass presenting with NSVT is broad but includes primary sarcoma or benign infiltrative tumors such as lipoma, fibroma, hemangioma, or hamartoma. Other rare etiologies include inflammatory masses due to cardiac sarcoidosis and giant cell myocarditis.

Investigations

Upon admission to the outside hospital, the patient underwent cardiac magnetic resonance (CMR) that revealed a LV mass infiltrating, but not distorting, the lateral wall and the anterolateral papillary muscle. Characteristics of the mass by CMR included similar signal to myocardium on T1-weighted sequences, increased signal on T2-weighted sequences, evidence of homogeneous perfusion on first-pass perfusion imaging, and heterogenous late gadolinium enhancement (LGE) (Figure 1).

Figure 1.

Cardiac Magnetic Resonance Imaging

Cardiac magnetic imaging (CMR) imaging revealing left ventricular mass in the lateral wall infiltrating the papillary muscles with isointense signal on T1-weighted sequence (A, asterisk), hyperintense signal on T2 STIR (short-tau inversion recovery) imaging (B), with homogenous perfusion on first-pass perfusion imaging (C) and heterogenous late gadolinium enhancement (D).

During admission at our institution, inpatient cardiac monitoring revealed frequent NSVT, as well as sustained ventricular tachycardia (VT) that localized on the electrocardiogram to the inferolateral LV wall, consistent with the LV mass location (Figure 2). The patient experienced palpitations during these episodes, without loss of consciousness or with hemodynamic instability. Transthoracic echocardiogram (TTE) at our institution confirmed a large LV hyperechoic mass involving the anterolateral papillary muscle and left lateral wall measuring approximately 5.6 × 1.9 cm (Figure 3).

Figure 2.

12-Lead Electrocardiogram

Twelve-lead electrocardiogram with sinus rhythm followed by spontaneous initiation of ventricular tachycardia with right bundle branch block morphology and right superior axis, with precordial transition in V₃-V₄ (midcavity) suspicious for papillary muscle origin.

Figure 3.

Transthoracic Echocardiogram

Transthoracic echocardiogram revealing homogenous hyperechoic left ventricular mass infiltrating the lateral wall without obvious echo contrast enhancement.

To further characterize the mass, a coronary computed tomographic angiography (CTA) was obtained (Figure 4). This revealed a lobulated LV mass measuring 5.2 × 2.1 cm involving the lateral wall and anterolateral papillary muscle. There was a nonenhancing central component that involved the papillary muscle and a heterogeneous enhancing component involving the intramyocardial lateral mass. No calcification or fat was noted within the mass. No extracardiac extension of the mass into the pericardium or mediastinum was noted. There was no evidence of early delayed iodine enhancement (2-minute delay) or evidence of disease spread beyond the myocardium. The coronary arteries were normal without evidence of atherosclerotic changes.

Figure 4.

Coronary Computed Tomographic Angiography

Coronary computed tomography angiography (CTA) with arterial and early delayed phases again demonstrating left ventricular mass, with a nonenhancing central component that involved the papillary muscle, and a heterogeneous enhancing component involving the intramyocardial lateral mass (A). No evidence of early delayed iodine enhancement (B).

Overall findings at this stage pointed towards a benign process, but given that a neoplastic process could not be entirely excluded, biopsy was pursued with TTE-guided transcatheter biopsy with a transaortic approach and cerebral embolic protection (Figure 5). Multiple biopsies were obtained at different levels of the visualized mass without complications. Frozen section evaluation confirmed adequate tissue for diagnosis.

Figure 5.

TTE-Guided Transcatheter Biopsy of LV Mass via Transaortic Approach

Permanent histologic sections of paraffin-embedded tissue revealed aggressive mononuclear inflammatory cell infiltration of the myocardium with multinucleated giant cells and fibrotic tissue with mononuclear infiltrates and necrosis (Figure 6). There were no tight granulomas. Eosinophils were few. In situ hybridization for Epstein-Barr virus–encoded small RNA to rule out a lymphoproliferative disorder was negative. Immunohistochemical stains showed abundant CD3⁺ T cells and CD68⁺ macrophages. There was no evidence of bacteria on tissue Gram stain, fungi on Grocott-Gomori silver and periodic acid-Schiff stains, or acid-fast bacilli on Ziehl-Neelsen stain. In the absence of microorganisms, a diagnosis of noninfectious granulomatous myocarditis was made. Clinically, this was supported by the absence of preceding respiratory or gastrointestinal symptoms or animal exposures. There were no sick contacts or recent travel. Infectious work-up including viral serologies for human immunodeficiency virus, hepatitis B and C, Lyme serology, cytomegalovirus, and blood Mycobacterium tuberculosis screening were all negative. Thus, the overall findings were consistent with noninfectious granulomatous myocarditis, most likely necrotizing sarcoidosis.

Figure 6.

Permanent Histologic Section

Left ventricular (LV) endomyocardial biopsy (left) shows a large fragment of tissue infiltrated by mononuclear cells with necrosis (upper right) and multinucleated giant cells (lower right). Asterisk represents zoomed-in location.

Finally, cardiac and whole-body positron emission tomography (PET) with F18-fluorodeoxyglucose (FDG) were obtained to guide current and future medical management. This confirmed intense focal FDG uptake involving the lateral and inferolateral wall with extension into the papillary muscles with a maximum standardized uptake value (SUV) of 10.9 and a background blood pool SUV of 1.2 (Figure 7). No other myocardial FDG uptake or extracardiac FDG uptake was noted (Figure 8). There was no evidence of extracardiac lymphadenopathy. The patient underwent eye exam, neurological evaluation, and skin exam without pathologic findings. In addition, serum creatinine, liver function tests, serum calcium, and vitamin D levels were all normal, pointing to the presence of isolated cardiac sarcoidosis.

Figure 7.

F18-FDG PET for Sarcoidosis Evaluation

F18-fluorodeoxyglucose (F18-FDG) positron emission tomography (PET) revealing large amount of inflamed myocardium with a focal distribution and affecting the lateral and inferolateral walls with extension to the papillary muscles (arrow) (top: rest perfusion imaging; bottom: FDG metabolic imaging).

Figure 8.

Coronal and Sagittal Whole-Body F18-FDG PET Showing Lack of Extracardiac F18-FDG Uptake

Abbreviations as in Figure 7.

Management

Throughout admission, given ongoing VT and NSVT, the patient was managed primarily with antiarrhythmic medications including lidocaine infusion and sotalol. On admission day 13, the patient underwent subcutaneous implantable cardioverter-defibrillator implantation. Following biopsy and PET on hospital days 20 and 25, respectively, the patient was started on methylprednisolone (1 g daily for 3 days) on hospital day 27. He was then transitioned to prednisone 30 mg per day. He was eventually discharged home on day 32, on mexiletine, amiodarone, prednisone, methotrexate, folic acid, pantoprazole, and sulfamethoxazole-trimethoprim.

Discussion

Cardiac masses are rare with an estimated incidence of 0.002% to 0.3% based on autopsy data.¹ The most frequent cardiac tumors are benign primary cardiac tumors, specifically atrial myxomas. The left ventricle is infrequently affected by cardiac masses, but when infiltrated can manifest with arrhythmia, conduction system disturbance, valvular dysfunction, and heart failure.² The differential diagnosis for LV tumors is broad, but traditional teaching has included thrombus, fibromas, rhabdomyoma, hemangioma, lipoma, sarcomas, and metastasis.³ Diagnosing and managing LV masses is often challenging due to relatively low accessibility for tissue diagnosis and high risk associated with biopsy. Advances in multimodality cardiac imaging have improved the diagnostic accuracy of cardiac masses and is currently used to better characterize them.

Cardiac sarcoidosis (CS) is often referred to as the great mimicker for a good reason. Although it traditionally presents with ventricular arrhythmia, heart failure, conduction abnormalities, or sudden cardiac death, few case reports have described it manifesting as a cardiac tumor.^4,5 Multimodality imaging can help establish this diagnosis, but tissue biopsy or extracardiac findings are necessary to confirm the diagnosis.

Although TTE remains the first-line imaging tool for the evaluation of cardiac masses, CMR has become the standard reference for tissue characterization and anatomic delineation.⁶ Other modalities such as CTA provide anatomical detail of cardiac and extracardiac structures, and presence of vascularity (enhancement), fat, and calcification, whereas PET provides cardiac and extracardiac metabolic characterization and perfusion but is limited by low spatial resolution.⁷

In our case, based on the presence of homogenous perfusion on CMR, heterogeneous LGE, isointense signal on T1-weighted imaging, and hyperintense signal on T2 STIR (short-tau inversion recovery) imaging; in addition to coronary CTA findings of no significant extracardiac extension, the working diagnosis pointed to a localized benign process.⁸ However, the possibility of a neoplastic process could not be entirely ruled out. Hence, a tissue biopsy was necessary to establish the diagnosis, which to our surprise was isolated cardiac sarcoidosis. In retrospect, the CMR showed evidence of myocardial edema (T2 STIR positivity) and inflammation/fibrosis (LGE) that should have prompted the suspicion for noninfectious myocarditis.

Although the differential diagnosis of noninfectious granulomatous myocarditis is broad, the more common causes are sarcoidosis and giant cell myocarditis. Less common causes include rheumatoid arthritis, hypersensitivity myocarditis, granulomatosis with polyangiitis, rheumatic fever, and foreign-body reaction; all were ruled out clinically. Distinction between cardiac sarcoidosis and giant cell myocarditis may not always be possible on histologic evaluation; however, the extent of fibrosis and only few eosinophils present in the biopsy favored sarcoidosis. Although it is admittedly rare to have unifocal LV involvement of CS,⁹ the formation of a mass localized to the lateral wall and anterolateral papillary muscle also favored sarcoidosis because this location is almost always involved in cardiac sarcoidosis.¹⁰

Finally, our patient had extensive evaluation without evidence of extracardiac sarcoidosis leading to the diagnosis of isolated CS, a rare entity of questionable existence with an estimated prevalence of up to 25% based on autopsy data and cohort studies.¹¹ Our case adds to the isolated CS literature, which has previously reported that patients with isolated CS have higher rates of VT and device therapy and lower LV systolic function compared with patients with systemic disease suggestive of a true, though rare, entity.^12,13

Follow-up

F18-FDG PET was repeated 3 months after initial PET to guide immunosuppressive therapy and revealed an interval decrease in FDG uptake but persistent focal uptake in the lateral wall, with SUV of 3.4 and a background blood pool SUV of 1.4 (Figure 9). Uptake of the papillary muscle was no longer present. TTE performed 6 months after discharge demonstrated resolution of LV mass (Figure 10). Prednisone was tapered with the addition of adalimumab, while continuing methotrexate. Given the persistent focal inflammation at repeat PET scan, the patient remains on low-dose amiodarone and mexiletine, and is arrhythmia-free on his 3-month device and electrophysiology follow-up.

Figure 9.

Follow-Up F18-FDG PET

Follow-up F18-FDG PET with interval decrease in focal FDG uptake of the lateral left ventricular wall no longer extending into the papillary muscle. Abbreviations as in Figure 7.

Figure 10.

Follow-Up Transthoracic Echocardiogram

Follow up transthoracic echocardiography (TTE) 6 months after discharge showing resolution of left ventricular mass (left, parasternal long axis; right, apical 4-chamber).

Conclusions

Cardiac sarcoidosis is the great mimicker and may present as an arrhythmogenic cardiac tumor.

Funding Support and Author Disclosures

Dr Logan has received support from National Institute on Minority Health and Health Disparities grant K23MD017284. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.