What is the treatment for cardiac sarcoidosis?

Treatment of Cardiac Sarcoidosis

Glucocorticoids (corticosteroids) are the mainstay of therapy for clinically relevant cardiac sarcoidosis and should be initiated promptly given the high mortality risk, particularly in patients with reduced left ventricular function, rhythm disturbances, or heart failure. 1, 2

Defining Clinically Relevant Cardiac Sarcoidosis

Treatment is indicated when patients have: 1

• Rhythm disturbances (ventricular tachycardia or significant conduction abnormalities)
• Heart failure symptoms
• High risk for sudden cardiac death

Even though evidence quality is very low with multiple confounders, the European Respiratory Society Task Force concluded that the danger of untreated cardiac sarcoidosis outweighs glucocorticoid toxicity risks. 1

Immunosuppressive Therapy

First-Line: Glucocorticoids

• Initial dosing: Prednisone 20-40 mg daily, typically started at high doses 2, 3
• Duration: Minimum 3-6 months, then taper slowly over 4-8 weeks if improvement occurs 3
• Mechanism: Suppresses inflammation and granuloma formation 2
• Efficacy: Associated with 75% five-year survival rate and improvement in left ventricular ejection fraction 2, 1

Second-Line: Steroid-Sparing Agents

Methotrexate is the preferred second-line agent when patients cannot tolerate corticosteroids or continue to worsen despite treatment. 2, 3

• A retrospective study showed that adding methotrexate to prednisone improved ejection fraction and brain natriuretic peptide after 5 years compared to prednisone alone 1
• Other options include azathioprine, mycophenolate mofetil, and cyclophosphamide (Level of Evidence C) 2
• Regular laboratory monitoring is required for toxicity 3

Third-Line: Anti-TNF Biologics

Infliximab is the preferred biologic for refractory disease that has failed corticosteroids and methotrexate. 2, 3

• Usually used in combination with second-line agents 1
• Adalimumab is an alternative anti-TNF option 1

Cardiac-Specific Management

Heart Failure Treatment

Standard guideline-directed medical therapy for heart failure with reduced ejection fraction should be implemented (Level of Evidence B): 2

• ACE inhibitors or ARBs
• Beta-blockers
• Aldosterone antagonists

Device Therapy

Implantable cardioverter-defibrillator (ICD) placement is reasonable for patients with cardiac sarcoidosis (Level of Evidence C). 2

• Consider waiting ≥6 months of medical therapy to allow for myocardial recovery before permanent device placement 1
• Wearable defibrillator vests may bridge patients with LVEF <35% during this observation period 1
• Cardiac resynchronization therapy (CRT) should be considered when ventricular function fails to normalize 1

Advanced Therapies

Referral for cardiac transplantation or mechanical circulatory support should be made for patients with advanced heart failure without significant extracardiac sarcoidosis (Level of Evidence C). 2

Prognostic Risk Stratification

High-risk features that influence treatment intensity include: 1

• Age >50 years
• Left ventricular ejection fraction <40%
• NYHA Functional Class III or IV
• Increased left ventricular end-diastolic diameter
• Late gadolinium enhancement on cardiac MRI
• Ventricular tachycardia
• Cardiac inflammation on FDG-PET scan
• Abnormal global longitudinal strain on echocardiography
• Interventricular septal thinning
• Elevated troponin or brain natriuretic peptide

Monitoring Treatment Response

Imaging Surveillance

Cardiac MRI or FDG-PET imaging is useful to diagnose cardiac sarcoidosis and follow response to therapy (Level of Evidence B). 2

• These modalities assess both inflammation (active disease) and fibrosis (chronic damage) 4, 5
• Echocardiography should be performed to assess left ventricular ejection fraction in patients with heart failure symptoms (Level of Evidence C) 2

Functional Assessment

• Monitor pulmonary function tests (FVC and DLCO) 3
• Track symptom improvement and quality of life measures 3
• Treatment may be discontinued if disease has been stable for 2-3 years 3

Critical Pitfalls to Avoid

The major pitfall is delayed diagnosis and treatment, as cardiac sarcoidosis can present with sudden cardiac death. 6, 7 Historical series showed 60% five-year mortality in untreated patients, which has improved dramatically with appropriate anti-inflammatory therapy and cardiac interventions. 6

Asymptomatic patients with concerning imaging features (late gadolinium enhancement, FDG uptake, T2 prolongation, or impaired global longitudinal strain) represent an area of current uncertainty, even when cardiac function is preserved and electrical abnormalities are absent. 1 The Task Force acknowledges this gap but leans toward treatment given the high stakes.

Isolated cardiac sarcoidosis without pulmonary involvement occurs in approximately 5% of patients and is particularly challenging to diagnose. 1 Maintain high clinical suspicion in patients with unexplained cardiomyopathy or arrhythmias. 5