The following are key points to remember from an American Heart Association (AHA) scientific statement on the diagnosis and management of cardiac sarcoidosis (CS):

Pathophysiology and Epidemiology

1. While the exact cause of sarcoidosis remains unknown, this systemic inflammatory disease likely develops due to exposure to an unknown antigen (such as mold, insecticides, or silica dust) in patients with genetic predisposition. Family history of sarcoidosis is associated with an increased risk of developing the condition.
2. The immune system dysregulation begins with the activation of type 1 T-helper cells and up-regulation of cytokines and chemokines. This leads to activation of macrophages and formation of non-necrotic inflammatory (so-called noncaseating) granulomas. An active inflammatory phase may progress to a fibrotic phase, both of which may contribute to cardiac dysfunction.
3. In the United States, systemic sarcoidosis has a prevalence of 35.2 cases per 100,000 population with higher incidence and prevalence in Black Americans. The prevalence of systemic sarcoidosis is higher in women compared with men. CS is particularly prevalent in the Japanese population. Heart failure (HF) is more common in Black individuals compared with White individuals and in women compared with men, whereas ventricular arrhythmias (VAs) have been reported to be more frequent in men than in women.

Diagnosis

1. Some “red flags” that should trigger consideration of CS include unexplained high-grade atrioventricular block in an individual <60 years of age, unexplained VA, reduced left ventricular ejection fraction (LVEF), regional wall aneurysm, or basal septal thinning in the absence of coronary artery disease or another explanation.
2. Cardiac magnetic resonance (CMR) has emerged as a key diagnostic test for CS. In a meta-analysis, CMR had a high sensitivity (95%) and specificity (85%) for the diagnosis of CS. Myocardial late gadolinium enhancement (LGE) is the strongest predictor for all-cause mortality and sustained VA among individuals with known or suspected CS. Common locations of CS involvement are LV subepicardial, septal, LV multifocal, or right ventricular (RV) free wall; still there are no patterns of LGE that are sufficient for the diagnosis of CS.
3. Fluorodeoxyglucose–positron emission tomography (FDG-PET) can identify metabolically active, inflammatory lesions in CS. The test requires a minimum of 24-hour fasting or carbohydrate-deprived diet to suppress the background myocardial uptake of FDG. Specific patterns, such as multiple noncontiguous perfusion defects with associated FDG uptake or multifocal FDG uptake in combination with extracardiac FDG uptake, have a sensitivity and specificity of 83% and 100%, respectively.
4. Because of the focal and patchy nature of the disease, unguided endomyocardial biopsy has a low sensitivity of approximately 20%. Both FDG-PET or CMR imaging and voltage map–guided biopsy procedures increase the diagnostic yield to 40-50%. Over the last three decades, the Japanese Ministry of Health and Welfare, World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG), Heart Rhythm Society (HRS), and the Japanese Circulation Society have proposed diagnostic criteria with which one may diagnose CS in the absence of a positive cardiac biopsy if extracardiac tissue diagnosis is present. Lung or lymph node biopsy is pursued most commonly. The most recent Japanese guideline is unique in that it does not require biopsy evidence of noncaseating granulomas, and it is the only guideline to include an imaging diagnostic algorithm for isolated CS.

Treatment

1. In general, if the patient is symptomatic, immunosuppression should be initiated in those with definite and highly probable CS. For the probable group, there should be careful discussion with the individual about the risks versus benefits of treatment. For those in the possible/low-probability group, treatment would generally not be pursued. Symptomatic CS can relapse when corticosteroids are tapered in as high as 75% of individuals. Methotrexate, mycophenolate, azathioprine, infliximab, adalimumab, and rituximab can reduce the lowest effective corticosteroid dose. There are no prospective randomized trials to compare the efficacy of immunosuppression. Although there is no perfect method to assess the degree of inflammation, cardiac FDG uptake correlates well with clinical evidence of active CS.
2. Although HF guideline-directed medical therapy has not been prospectively studied in individuals with CS cardiomyopathy, the benefits of these medications are extrapolated from existing studies in individuals with HF.
3. Conduction system abnormalities are common in CS. Individuals with heart block caused by CS have a high risk of VA, heart transplantation, or cardiac death. The underlying mechanism of VA in CS can be autonomic, triggered, or re-entry, depending on the inflammatory to fibrotic phase of granulomatous infiltration, and the variability in mechanisms mandates a comprehensive approach to therapy comprising immunosuppression, antiarrhythmic medications, and ablation.
4. In the 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death, implantable cardioverter-defibrillator implantation in CS has a Class I recommendation for secondary prevention and a Class I recommendation for primary prevention of sudden cardiac death in individuals who have LVEF ≤35%. Additional Class IIa recommendations include individuals with CS and LVEF of 36-49% or RVEF <40%, syncope or myocardial scar on CMR imaging or FDG-PET, indication for permanent pacing, or inducible sustained ventricular tachycardia at electrophysiology study.
5. A multidisciplinary team approach for accurate diagnosis, treatment, and comprehensive care is recommended. The multidisciplinary team may comprise an advanced HF cardiologist, electrophysiologist, advanced cardiac imager, pulmonologist, rheumatologist, and other extracardiac organ–specific specialists such as a neurologist or ophthalmologist, as well as advanced practice professionals.

Future Directions

There are significant unmet needs in the optimal diagnostic and management strategies in sarcoidosis. We need higher-quality evidence to guide the use of these therapies, which may be expensive and have potential for harmful side effects.

Clinical Topics: Heart Failure and Cardiomyopathies, Arrhythmias and Clinical EP

Keywords: Sarcoidosis, Cardiomyopathies

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