What is the best management approach for a patient with cardiac sarcoidosis, left ventricular dysfunction, and a left ventricular ejection fraction (LVEF) of 15%, who is already on oral prednisolone (corticosteroid) therapy?

Management of Cardiac Sarcoidosis with LVEF 15% on Prednisolone

This patient requires immediate ICD implantation for primary prevention of sudden cardiac death, continuation of prednisolone therapy indefinitely, optimization of guideline-directed medical therapy for heart failure with reduced ejection fraction, and consideration for advanced heart failure therapies including cardiac transplantation evaluation. 1, 2

Immediate Device Therapy

An ICD is mandated in this patient with cardiac sarcoidosis and LVEF ≤35%. 1 The 2017 AHA/ACC/HRS guidelines provide a Class I, Level B-NR recommendation for ICD implantation in patients with cardiac sarcoidosis who have LVEF of 35% or less, provided meaningful survival of greater than 1 year is expected. 1 With an LVEF of 15%, this patient faces extremely high risk of sudden cardiac death from ventricular arrhythmias, which occurs regardless of initial clinical presentation. 1

• If the patient is not already hospitalized, consider a wearable cardioverter-defibrillator as a bridge during the initial 3-6 months of optimized medical therapy to allow for potential myocardial recovery before permanent device placement. 2
• Cardiac resynchronization therapy (CRT) should be considered if ventricular function fails to normalize and the patient meets standard CRT criteria (QRS duration ≥150 ms with LBBB morphology). 2

Immunosuppressive Therapy Management

Continue prednisolone indefinitely—do not discontinue corticosteroid therapy in this patient. 2, 3 The European Respiratory Society Task Force emphasizes that the danger of untreated cardiac sarcoidosis outweighs glucocorticoid toxicity risks, particularly in patients with reduced left ventricular function. 2

• Discontinuation of prednisolone is associated with significantly higher cardiac mortality (p=0.035) and greater percent decrease in LVEF (p=0.037) compared with continuation. 3
• Steroids do not reverse advanced ventricular dysfunction once present (LVEF 15% represents advanced dysfunction), but they prevent further deterioration and reduce arrhythmia burden when given early. 1
• Add methotrexate to the prednisolone regimen. 2 Retrospective data demonstrate that adding methotrexate to prednisone improved ejection fraction and brain natriuretic peptide after 5 years compared to prednisone alone. 2
• Alternative immunosuppressive agents (azathioprine, mycophenolate mofetil, cyclophosphamide) are reasonable if the patient cannot tolerate corticosteroids or continues to worsen despite treatment. 2

Heart Failure Optimization

Implement full guideline-directed medical therapy for heart failure with reduced ejection fraction immediately. 2 This takes priority alongside immunosuppression.

• Initiate an ACE inhibitor or ARB (if ACE inhibitor not tolerated) titrated to target doses. 1, 2
• Start a beta-blocker (carvedilol, metoprolol succinate, or bisoprolol) at low dose and uptitrate as tolerated—these reduce all-cause mortality by 35% and specifically reduce sudden death. 1
• Add a mineralocorticoid receptor antagonist (spironolactone or eplerenone)—these reduce sudden cardiac death by 23% (OR 0.77,95% CI 0.66-0.89, p=0.001). 1, 2
• Consider SGLT2 inhibitors to reduce risk of heart failure hospitalization and cardiovascular death. 2
• Loop diuretics for volume management as needed, though these do not reduce mortality. 1

Prognosis and Risk Stratification

This patient has multiple high-risk features that mandate aggressive therapy: 2

• LVEF <40% (this patient has 15%)
• Likely NYHA Functional Class III or IV given the severe systolic dysfunction
• High probability of late gadolinium enhancement on cardiac MRI and/or cardiac inflammation on FDG-PET scan
• Elevated troponin or brain natriuretic peptide expected

Most patients with cardiac sarcoidosis treated with corticosteroids maintain or improve LV systolic function (82% demonstrate stable or improved LVEF). 4 However, patients presenting with cardiomyopathy have worse survival without the composite endpoint of ventricular assist device placement, heart transplant, or death (log-rank = 0.005). 5

• Baseline reduced LVEF is significantly associated with reduced LVEF after treatment (OR 54.89,95% CI 3.84-785.09, p=0.003). 4
• Change in LVEF is significantly higher in patients with baseline reduced LVEF compared to preserved LVEF (5% vs 0%, p=0.001). 4

Advanced Heart Failure Evaluation

Refer immediately for cardiac transplantation evaluation. 2 With LVEF of 15%, this patient has end-stage heart failure and should be evaluated for mechanical circulatory support and transplantation without delay. 2

• Patients with cardiac sarcoidosis undergoing transplantation have better short- and intermediate-term survival than patients transplanted for other reasons. 2
• Sarcoidosis can recur in the transplanted heart as early as 24 weeks post-transplantation but usually responds to steroids. 2
• Ventricular assist device placement may be necessary as a bridge to transplantation if the patient deteriorates. 5

Monitoring Treatment Response

• Perform cardiac MRI or FDG-PET imaging to assess inflammation and scar burden, and to follow response to immunosuppressive therapy (Level of Evidence B). 2
• Repeat echocardiography every 3-6 months to assess LVEF trajectory and ventricular remodeling. 2
• Monitor for ventricular arrhythmias—15 of 22 patients (68%) presenting with ventricular arrhythmia had recurrence despite treatment. 5
• Check inflammatory markers and brain natriuretic peptide serially. 2

Critical Pitfalls to Avoid

• Never discontinue prednisolone in this patient—even if clinical improvement occurs, discontinuation leads to worsening LVEF and increased cardiac mortality. 3
• Do not delay ICD implantation waiting for LVEF improvement—the risk of sudden death is immediate and high. 1
• Avoid rapid steroid tapers, as this increases risk of disease relapse. 2
• Do not assume that immunosuppression alone will reverse the severe ventricular dysfunction—steroids are ineffective at reversing advanced LV dysfunction once wall thinning has occurred. 6
• Recognize that untreated cardiac sarcoidosis with active inflammation can lead to severe LV dysfunction and ventricular wall thinning within just 3 years. 6
• Be aware that worsening of ventricular arrhythmias has been reported with immunosuppressive therapy in some patients, including electrical storm developing within 12 months of initiating therapy. 1