What is the recommended treatment for cardiac sarcoidosis?

Treatment of Cardiac Sarcoidosis

For patients with cardiac sarcoidosis presenting with functional cardiac abnormalities (heart block, dysrhythmias, or cardiomyopathy), initiate glucocorticoids immediately at a starting dose of prednisone 0.5 mg/kg/day (maximum 30 mg daily), with early addition of steroid-sparing agents to minimize long-term corticosteroid toxicity. 1

Immunosuppressive Therapy Algorithm

First-Line Treatment: Glucocorticoids

• Start prednisone at 0.5 mg/kg/day (maximum 30 mg daily) for all patients with clinically manifest cardiac sarcoidosis 1
• Doses higher than 0.5 mg/kg/day provide no additional benefit 1
• Earlier initiation of glucocorticoids confers better cardiac outcomes, so do not delay treatment 1
• Glucocorticoid treatment reduces composite cardiac endpoints with hazard ratios ranging from 0.33 to 0.78 1
• Heart block responds particularly well to glucocorticoids and may be the manifestation with the best chance of improvement 1
• Never withdraw glucocorticoids abruptly after initiation, as this is associated with worse outcomes regardless of clinical improvement 1

Second-Line Treatment: Steroid-Sparing Agents

Initiate steroid-sparing medications early to minimize glucocorticoid toxicity, even though evidence quality is limited 1

Methotrexate is the preferred steroid-sparing agent:

• Dose: 10-15 mg once weekly 2, 3
• Adding methotrexate to prednisone improved ejection fraction and brain natriuretic peptide after 5 years compared to prednisone alone 1, 2
• Provide folate supplementation to reduce side effects 4

Alternative steroid-sparing agents include azathioprine, mycophenolate mofetil (500-1500 mg twice daily), leflunomide, and cyclophosphamide 1, 3

Third-Line Treatment: Biologic Agents

Infliximab for refractory disease:

• Dose: 5 mg/kg at weeks 0,2, and 6, then maintenance therapy 2, 4
• Infliximab-containing regimens achieve superior prednisone-tapering success (75%) compared to prednisone alone (27%) or prednisone plus methotrexate (13%) 5
• Infliximab regimens achieve the lowest effective prednisone dose (7.8 ± 4.9 mg) compared to other regimens 5
• Consider for patients with severe disease unresponsive to glucocorticoids and methotrexate 1, 4

Cardiac-Specific Management

Heart Failure Therapy

Implement standard guideline-directed medical therapy for heart failure with reduced ejection fraction immediately: 2

• ACE inhibitors or ARBs 2
• Beta-blockers (reduce all-cause mortality by 35% and sudden death) 2
• Mineralocorticoid receptor antagonists/aldosterone antagonists (reduce sudden cardiac death by 23%) 1, 2
• Loop diuretics for volume management as needed 2

Device Therapy

ICD placement is reasonable for all patients with cardiac sarcoidosis given the high risk of sudden cardiac death 2

• For LVEF ≤35%, ICD implantation is a Class I recommendation if meaningful survival >1 year is expected 2
• Do not delay ICD implantation waiting for LVEF improvement—the risk of sudden death is immediate and high 2
• Consider waiting ≥6 months of medical therapy to allow myocardial recovery before permanent device placement 2
• Use wearable defibrillator vests to bridge patients with LVEF <35% during this observation period 2

Cardiac resynchronization therapy (CRT) should be considered when ventricular function fails to normalize 2

Advanced Heart Failure

Refer for cardiac transplantation or mechanical circulatory support for patients with advanced heart failure without significant extracardiac sarcoidosis 2

• Patients with cardiac sarcoidosis have better short- and intermediate-term survival post-transplant than other indications 2
• Sarcoidosis can recur in the transplanted heart as early as 24 weeks but usually responds to steroids 2

Risk Stratification for Treatment Intensity

High-risk features that warrant aggressive treatment include: 1, 2

• Age >50 years 1, 2
• Left ventricular ejection fraction <40% 1, 2
• NYHA Functional Class III or IV 1, 2
• Increased left ventricular end-diastolic diameter 1, 2
• Late gadolinium enhancement on cardiac MRI 1, 2
• Ventricular tachycardia 1, 2
• Cardiac inflammation on FDG-PET scan 1, 2
• Abnormal global longitudinal strain on echocardiography 1, 2
• Interventricular septal thinning 1, 2
• Elevated troponin or brain natriuretic peptide 1, 2

Monitoring Treatment Response

Use cardiac MRI or FDG-PET imaging to diagnose cardiac sarcoidosis and follow response to therapy 2

• These modalities are useful for both diagnosis and monitoring (Level of Evidence B) 2

Perform echocardiography to assess left ventricular ejection fraction in patients with signs and symptoms of heart failure 2

Evaluate treatment response after 3-6 months before making changes to the immunosuppressive regimen 4

Critical Pitfalls to Avoid

Asymptomatic patients with concerning imaging features (late gadolinium enhancement, FDG uptake, T2 prolongation, or impaired global longitudinal strain) represent an area of uncertainty, but treatment should be strongly considered given the high stakes even when cardiac function is preserved 1, 2

Isolated cardiac sarcoidosis without pulmonary involvement occurs in approximately 5% of patients and is particularly challenging to diagnose 2

Worsening of ventricular arrhythmias has been reported with immunosuppressive therapy in some patients, including electrical storm developing within 12 months of initiating therapy 2

Avoid long-term prednisolone monotherapy due to risk of disease progression and significant toxicity—always consider steroid-sparing agents 4

Do not make early treatment changes—allow a minimum of 3-6 months for evaluation of treatment response 4

Supportive Care

Prophylaxis and bone protection: 4

• Pneumococcal and influenza vaccination 4
• Consider Pneumocystis prophylaxis for patients on long-term high-dose steroids or multiple immunosuppressive agents 4
• Calcium and vitamin D supplementation 4
• Gastrointestinal prophylaxis with proton pump inhibitors 4