Sarcoidosis Masquerading as Hypertrophic Cardiomyopathy

Abstract

Background

Hypertrophic cardiomyopathy (HCM) and infiltrative cardiomyopathies are important causes of cardiogenic syncope with overlapping clinical and radiologic features.

Case Summary

A 49-year-old gentleman presented with syncope while walking across the Brooklyn Bridge. Electrocardiogram revealed low-voltage QRS with diffuse T-wave inversions. Echocardiography revealed moderate left ventricular hypertrophy, wall motion abnormalities with left ventricular ejection fraction 35% to 40%, and a dilated, hypokinetic right ventricle. Cardiac magnetic resonance showed biventricular hypertrophy and evidence of late gadolinium enhancement. Positron emission tomography/magnetic resonance (PET/MR) 18F-FDG revealed right ventricle uptake along with matching late gadolinium enhancement and FDG avidity in the hilar and mediastinal lymph nodes. Endomyocardial biopsy showed noncaseating granulomas, confirming sarcoidosis. An implantable cardioverter-defibrillator was inserted. Despite immunosuppression and guideline-directed medical treatment, the patient eventually required cardiac transplantation.

Discussion

Cardiac sarcoidosis mimicking genetic cardiomyopathy, and vice versa, has often been reported. Combined PET/MR helped distinguish these pathologies in our patient.

Take-Home Messages

Cardiac sarcoidosis can mimic HCM; multimodal imaging, including PET/MR, guided by clinical suspicion, is important. Biventricular involvement in HCM is infrequent.

Visual Summary

A 49-year-old male, with no significant medical history, presented following an episode of syncope while walking on the Brooklyn Bridge. The family history was noted to be unremarkable. Upon admission, the patient's vital signs were stable. A physical examination revealed jugular venous distension without lung crepitations or signs of lower-extremity edema. Laboratory testing indicated the presence of iron deficiency anemia. A comprehensive metabolic panel, which included calcium and serum angiotensin-converting enzyme, demonstrated results within normal limits. The troponin and brain natriuretic protein levels were mildly elevated: 101 ng/dL (normal 0-35 ng/L) and 100 pg/mL (0-100 pg/mL), respectively. Although the differential for syncope is broad, in our young and otherwise healthy patient who had no features suggestive of seizure, no preceding positional change or orthostatic medications, no vasovagal triggers, a prodrome of dyspnea and dizziness, short duration of syncope, seemingly quick recovery, and signs of right-sided cardiac dysfunction, cardiogenic syncope was a concern.

Take-Home Messages

• •Cardiac sarcoidosis may mimic other genetic cardiomyopathies, including hypertrophic cardiomyopathy. However, biventricular involvement of hypertrophic cardiomyopathy is rare and infrequent.
• •Multimodal imaging guided by clinical suspicion is valuable when nonischemic cardiomyopathy is suspected, particularly simultaneous positron emission tomography/magnetic resonance as it enables immediate correlation between scarring and inflammatory activity.

The electrocardiogram (Figure 1A) showed sinus rhythm, low-amplitude QRS complexes, and T-wave inversions localized to the anterior and inferior leads. Telemetry demonstrated episodes of nonsustained ventricular tachycardia. In light of the T-wave inversions and elevated troponin levels, cardiac catheterization was performed, which revealed nonobstructed coronary arteries and normal right-sided pressures but indicated a reduced cardiac output of 1.9 L/min/m².

Figure 1.

Electrocardiogram

This revealed low-amplitude QRS complexes, accompanied by T-wave inversion.

The transthoracic echocardiogram demonstrated moderately reduced left ventricular (LV) systolic function, with an ejection fraction of 40%. In addition, moderate asymmetric left ventricular hypertrophy and wall motion abnormalities were observed, affecting the basal anteroseptal, basal inferoseptal, mid-anteroseptal, and mid-inferoseptal walls. Given the presence of asymmetric left ventricular hypertrophy, cardiovascular magnetic resonance imaging (CMR) was pursued, which confirmed severe asymmetric LV hypertrophy, with a maximum wall thickness of 1.6 cm at the basal septum. Notably, there was also right ventricular (RV) hypertrophy, dilation, and systolic dysfunction. Furthermore, there was extensive patchy late gadolinium enhancement (LGE) in both the basal to apical LV septal and inferior segments, alongside diffuse RV involvement.

Initial clinical considerations suggested a potential diagnosis of hypertrophic cardiomyopathy, RV predominant variant, based on the asymmetric septal hypertrophy evidenced in both the transthoracic echocardiogram and CMR.^1,2 However, because of the lack of electrocardiographic evidence of hypertrophy and the small voltages of the QRS coupled with RV hypertrophy and associated wall motion abnormalities, an infiltrative process was suspected, and the patient underwent hybrid 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). This contemporary approach was chosen to facilitate a comprehensive assessment of cardiac inflammation and metabolic activity. The findings revealed prominent myocardial FDG uptake along with LGE and demonstrated FDG avidity in the hilar and mediastinal lymph nodes, adding valuable information to the overall clinical picture (Figure 2).

Figure 2.

Hybrid PET/MRI

This demonstrated increased FDG uptake in the right ventricle, accompanied by LGE. FDG = hybrid 2-deoxy-2-[fluorine-18]fluoro-D-glucose; LGE = late gadolinium enhancement; MRI = magnetic resonance imaging; PET = positron emission tomography.

The diagnosis of cardiac sarcoidosis was later confirmed via endomyocardial biopsy, which exhibited noncaseating granulomas. The patient was initiated on immunosuppressive therapy in conjunction with guideline-directed medical treatment and the placement of an implantable cardioverter-defibrillator. A subsequent PET scan indicated persistent active cardiac sarcoidosis, and the patient experienced repeated hospitalizations for heart failure, ultimately necessitating cardiac transplantation.

Sarcoidosis is a multisystem inflammatory disorder characterized by a dysregulated T-cell response and the formation of noncaseating granulomas. Cardiac involvement occurs in up to 20% of cases, although truly isolated cardiac sarcoidosis is considerably rarer.³ Hybrid PET/MRI is an emerging imaging modality that allows for the simultaneous evaluation of LGE and FDG uptake.^4,5 While the use of this technology has traditionally been more common in oncology, its application in cardiology is steadily increasing. The diagnosis of hypertrophic cardiomyopathy has risen significantly, largely due to greater awareness and improved access to cardiac magnetic resonance imaging. However, certain clinical features may point toward alternative diagnoses. Misdiagnosis can have serious consequences, affecting long-term management, increasing the risk of systemic complications, and potentially leading to adverse cardiovascular outcomes or death. CMR provides a detailed assessment of both left ventricular and RV function, and LGE, along with T1 and T2 mapping, enables quantification of myocardial fibrosis and edema. Although specific LGE patterns may suggest a particular diagnosis, their sensitivity is limited. Meanwhile, PET offers valuable insights into active myocardial inflammation, as indicated by 18F-FDG uptake, which can guide diagnosis, monitor response to immunosuppressive therapy, and inform treatment decisions. Simultaneous PET/MR provides the insight of both modalities in a single test and has been increasingly recognized as an important tool for the evaluation of cardiac pathologies, notably appearing in the 2024 American Heart Association/American College of Cardiology scientific statement for the diagnosis and management of cardiac sarcoidosis.³ In a recent study, PET/MR demonstrated superior diagnostic performance and safety compared to standard-of-care imaging consisting of separate cardiac MRI, PET/CT, and single-photon emission computed tomography.⁶ Moreover, there is evidence that PET/MR-based classification of cardiac sarcoidosis may provide valuable prognostic information.⁷ Overall, despite limited availability and the need for specialized expertise in image interpretation, hybrid PET/MR remains a promising tool in the evaluation of cardiomyopathies.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Visual Summary.

Case Timeline

Timeline	Events
First week	•Presents with syncope •ECG: anteroinferior TWI •TTE: LVEF 42%, asymmetric LVH, RV dysfunction
	•cMRI: severe asymmetric LVH, RV changes, and diffuse LGE •PET/MR: myocardial LGE & uptake, lymph node uptake
	•LHC: unobstructed coronaries •RHC: normal pressures but CO = 1.9 L/min •RV biopsy: noncaseating granulomas
	•Discharged with immunosuppression, initial GDMT, ILR, and LifeVest
∼1 mo later	•Single chamber ICD implantation
∼4 y later	•First ICD shock – interrogation reveals AF •LVEF 37%
∼6-8 y later	•LVEF 22%; GDMT advanced; worsened further to 18% •Repeat PET/CT scans: active cardiac sarcoid; immunosuppression resumed
	•Multiple admissions for arrhythmias including VT and AV block
	•Patient undergoes cardiac transplantation. Doing well post-transplant.

AF = atrial fibrillation; AV = atrioventricular; cMRI = cardiac magnetic resonance imaging; ECG = electrocardiogram; GDMT = guideline-directed medical therapy; ICD = implantable cardioverter-defibrillator; ILR = implantable loop recorder; LGE = late gadolinium enhancement; LHC = left heart catheterization; LVEF = left ventricular ejection fraction; LVH = left ventricular hypertrophy; PET/MR = positron emission tomography/magnetic resonance; RHC = right heart catheterization; RV = right ventricle; TTE = transthoracic echocardiography; TWI = T-wave inversion; VT = ventricular tachycardia.