A Challenging Case of Advanced Cardiac Sarcoidosis Refractory to Infliximab Therapy

ABSTRACT

Cardiac sarcoidosis can be life‐threatening, and lack of response to immunosuppressive therapy remains a significant challenge in active disease. We present a case of refractory cardiac sarcoidosis despite third‐line immunosuppression (infliximab). Ongoing multimodality assessment is essential for managing refractory cardiac sarcoidosis.

1. Introduction

Cardiac sarcoidosis (CS) is an inflammatory cardiomyopathy that affects up to 30% of all sarcoidosis patients [1]. Unopposed myocardial inflammation drives fibrosis, with consequential morbidity and mortality secondary to ventricular dysfunction, arrhythmogenesis and high‐grade atrioventricular block [2]. Diagnosis can be made following presence of an extra‐cardiac biopsy confirming systemic sarcoid, alongside advanced imaging modalities suggestive of cardiac involvement (namely Echocardiographic, Cardiac Magnetic Resonance Imaging (cMRI) and 18F‐fludeoxyglucose‐18 positron emission tomography (FDG‐PET)) [3, 4, 5]. Immunosuppressive therapies form the primary basis of initial disease management where active inflammation is apparent. Current European consensus guidelines recommend the use of steroids as first line therapies, alongside consideration of steroid‐sparing agents such as Methotrexate (MTX) [5]. In refractory cases with poor response, initiation of biologic agents (such as Infliximab) can be considered; however, the overall evidence base is limited and concerns persist regarding the possibility of exacerbating left ventricular (LV) systolic dysfunction [6]. The Cardiac Sarcoidosis Service at the Royal Brompton Hospital (RBH), part of Guy's and St Thomas' NHS Foundation Trust, is one of the largest CS centres globally. In this case report, we describe a challenging case of CS refractory to conventional and advanced immunosuppressive therapy using Infliximab.

2. Patient Presentation

This case involves a 35 year‐old male of Afro‐Caribbean ancestry, who had a confirmed diagnosis of CS. He initially presented with uveitis in 2022, and shortly thereafter developed sustained ventricular tachycardia (sVT) necessitating emergency hospitalization. Multimodality imaging raised suspicion of underlying CS, with evidence of myocardial inflammation on FDG PET but preserved LV function. Due to lymph node avidity on FDG PET, an endobronchial ultrasound guided biopsy was performed, ultimately confirming extra‐cardiac sarcoidosis. He underwent secondary prevention implantable cardiac defibrillator (ICD) insertion in 2023.

Several weeks following ICD implantation, he received appropriate device shocks for sVT. Initial immunosuppressive management was started shortly thereafter—with 3 days of IV Methylprednisolone and subsequent initiation of oral Prednisolone and methotrexate as shown in Figure 1.

FIGURE 1.

Timeline events of the progression of cardiovascular symptoms and decline in left ventricular function.

Following several months of steroid therapy, repeat TTE (Figure 2, Videos S1 and S2) revealed moderate to severe LV systolic dysfunction along with segmental wall motion abnormalities and repeat FDG PET imaging demonstrated persistent diffuse left ventricular and right atrial inflammation (Figure 3a–c). cMRI imaging was also performed, and demonstrated now‐moderately impaired LV function, with thinning and hypokinesis of basal inferior and infero‐septal walls. T1 and T2 mapping values were elevated in these regions suggestive of ongoing inflammation, alongside established fibrotic changes detected by the presence of late gadolinium enhancement (LGE) in a subendocardial/near transmural distribution (Figure 4).

FIGURE 2.

Echo videos on 2024 of (a) parasternal view and (b) apical 4 chamber view demonstrates mod‐severe LVSD, with RWMAs akinetic basal, and mid inferoseptal wall (not uploaded here).

FIGURE 3.

(a–c) Serial FDG PET images from June 2023, August 2024 and January 2025, demonstrating persistent inflammatory changes and increased FDG‐uptake in the basal lateral wall of the left ventricle and right atrium despite immunosuppressive therapy.

FIGURE 4.

cMRI images from 2023; there is subendocardial/near transmural LGE in the basal inferior and inferoseptal segments.

3. Management

The patient was initiated on guideline directed medical therapy (GDMT) including beta‐blocker, ARNI, MRA, SGLT2 inhibitor for his LV systolic dysfunction. He was discussed at the Cardiac Sarcoidosis multidisciplinary team meeting (MDT) – given the persistent inflammation despite intense steroid therapy, the decision was made to initiate IV infliximab at 5 mg/kg every 6 weeks, alongside Methotrexate whilst weaning his oral steroids. Monitoring bloods after Infliximab initiation demonstrated evidence of neutropenia (absolute neutrophil count: 0.6x × 10⁹/L), and raised inflammatory markers, which necessitated interruption of therapy and IV antibiotics to control infection.

Unfortunately, in 2024 he re‐presented with further appropriate ICD shocks for sustained ventricular tachycardia (sVT). During his stay, VT shocks have settled with antiarrhythmic medications including beta‐blockers (Nadolol 120 mg BD), in view of no increase scar burden on CMR, VT ablation was not considered Repeat FDG‐PET imaging, performed following completion of Infliximab therapy, demonstrated likely persistent diffuse FDG activity (Figure 3a–c).

3.1. Follow Up

Patient was re‐discussed at the sarcoidosis multidisciplinary team meeting. The case was reviewed with particular consideration of alternative immunomodulatory therapies. Rituximab was proposed as a potential option which may help stabilize cardiac function and reduce arrhythmia burden in refractory CS.

However, in view of the worsening cardiac function, persistently elevated NT‐proBNP, refractory arrhythmia, and evidence of ongoing active sarcoid inflammation despite third‐line immunosuppressive therapy, the overall clinical picture is consistent with advanced heart failure.

On this basis, it was recommended to proceed with referral to the transplant team for formal assessment.

4. Conclusion

In conclusion, we demonstrate a case of CS with evidence of refractory inflammation despite third‐line IV Infliximab use. It is of utmost importance that appropriate imaging modalities and clinical monitoring are utilized when advanced immunosuppressive agents are required in CS, so that appropriate referral to the tertiary transplant setting can ultimately be considered alongside less commonly used immunomodulatory therapies.

5. Discussion

In this case report, we describe a young patient with refractory cardiac sarcoidosis defined as persistent FGD activity despite third line immunosuppression. The persistent myocardial inflammation noted on FDG PET imaging corresponded with worsening heart failure resulting in repeated sVT and device shocks [7]. Appropriate referral to a cardiac transplant centre has been sought.

Infliximab is a tumor necrosis factor‐alpha (TNF‐α) inhibitor, recommended for use in CS cases with ongoing inflammation despite treatment with steroid and/or steroid sparing agents [5]. Numerous case series have demonstrated its successful utility in CS refractory to first‐line immunosuppressive treatment [8]. In one of the largest series in literature, Harper et al. described Infliximab use in 36 patients who had refractory inflammation despite first‐line immunosuppressive therapies. The authors noted significant reductions in baseline oral steroids, borderline significant reductions in ventricular arrhythmias, but no overall significant differences in LV function after 6 months. Some patients did demonstrate adverse side effects—one had decompensated LV function necessitating Infliximab discontinuation, and 5 developed significant infections. However, of note, myocardial inflammation on FDG PET was not assessed in this study [6].

Overall, failure of response in this case report was measured by ongoing inflammatory changes detected by FDG PET, alongside recurrent sVT culminating in ICD shocks. Such reports in literature are very rare [8]. It is difficult to ascertain whether the presence of persistent inflammatory activity or the utility of IV Infliximab in this case was responsible for the deterioration in LV function noted. There are nonetheless reports of LV impairment following (TNF‐α) usage and caution in appropriate imaging and monitoring is prudent [6].

Finally, in this instance, immunomodulatory therapy using Rituximab (a monoclonal antibody targeting CD20) is now being considered, given its mechanism of B‐cell depletion. Reports in literature have highlighted its potential role in reducing myocardial inflammation in CS cases refractory to conventional immunosuppressive therapies [9].

Author Contributions

Vasileios Kouranos: supervision, conceptualization, writing – review and editing. Manal Ibrahim: writing – original draft, writing – review and editing, conceptualization, methodology, formal analysis. Kshama Wechalekar: data curation, investigation, resources, writing – review and editing. Rakesh Sharma: supervision, conceptualization, resources, writing – review and editing. Mansimran Singh Dulay: writing – original draft, writing – review and editing, methodology, formal analysis.

Funding

The authors have nothing to report.

Consent

Verbal and written consent with the patient was made to publish this anonymized case report, in accordance with COPE guidelines.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Video S1: Apical view for refractory sarcoid case.

Video S2: PARASTERNAL and apical as viewed demonstrates mod‐severe LVSD, with RWMAs akinetic basal and mid inferoseptal wall.

Ibrahim M., Dulay M. S., Wechalekar K., Kouranos V., and Sharma R., “A Challenging Case of Advanced Cardiac Sarcoidosis Refractory to Infliximab Therapy,” Clinical Case Reports 14, no. 8 (2026): e73227, 10.1002/ccr3.73227.

Data Availability Statement

The data that supports the findings of this study are available in the Supporting Information of this article.