What is the recommended treatment for myositis patients with suspected cardiac involvement?

Cardiac Involvement in Myositis: Critical Clinical Considerations

Cardiac involvement in myositis is a potentially fatal complication that demands systematic cardiac screening in every patient with suspected or confirmed myositis, as myocarditis significantly increases mortality risk (approximately 20% vs <10% in idiopathic inflammatory myositis without cardiac involvement). 1

Why Cardiac Screening is Mandatory

Myocarditis frequently co-occurs with immune-related myositis and represents the primary driver of mortality in these patients. 1 The critical issue is that normal cardiac enzymes cannot always rule out myocarditis, making comprehensive cardiac evaluation essential even when initial biomarkers appear reassuring. 1

Timing and Presentation

• Myositis with cardiac involvement typically occurs early after immune checkpoint inhibitor initiation (median 25 days, IQR 25-45 days). 1
• Life-threatening manifestations include dyspnea, palpitations, chest pain, or syncope—any of these symptoms should immediately trigger suspicion for concurrent myocarditis. 1

Systematic Cardiac Evaluation Protocol

Every patient with myositis or suspected myositis must undergo:

Initial Screening (All Patients)

• Cardiac troponin (troponin I is more specific than troponin T when skeletal muscle disease is present). 1
• Electrocardiography to detect QTc prolongation, new conduction disease, or ST-T wave changes. 1
• BNP measurement (levels >500 pg/ml indicate significant concern). 1

Advanced Imaging When Indicated

• Cardiac MRI is necessary if clinical syndrome suggests myocarditis, cardiac troponin is elevated, or ECG shows abnormalities. 1
• Cardiac MRI serves as both a diagnostic and monitoring tool for myocardial inflammation, showing marked reduction in contrast enhancement and hypokinesia after appropriate treatment. 2

Additional Monitoring

• Echocardiography to assess wall motion abnormalities or wall thickening. 3
• Baseline ECG and cardiac biomarker assessment should be established before therapy to identify notable changes during treatment. 1

Clinical Red Flags Beyond Cardiac Symptoms

Neuromuscular Complications

• Bulbar symptoms (dysphagia, dysarthria, dysphonia) or respiratory failure may indicate myositis severity or associated myasthenia gravis (present in 12.5% of cases). 1
• Ptosis and diplopia commonly signal associated myasthenia gravis. 1
• Dropped head syndrome can occur. 1

Laboratory Markers

• Creatine kinase (CK) elevation is seen in the majority of myositis patients (median 2650 IU/L, range 335-20,270 IU/L). 1
• CK levels are typically normal in patients with myalgia alone, helping distinguish true myositis from muscle pain. 1
• Transaminases (AST, ALT), LDH, and aldolase may also be elevated. 1

Treatment Implications Based on Cardiac Involvement

When Myocarditis is Confirmed or Strongly Suspected

Patients with confirmed myocarditis (or reasonable suspicion) should receive emergent high-dose corticosteroids. 1 The decision to start corticosteroids in possible (versus confirmed) myocarditis should be made case-by-case until data on specific troponin cut-off levels become available. 1

Grade 4 (Life-Threatening) Management

• Permanently discontinue immune checkpoint inhibitors. 1
• High-dose corticosteroids: 1 mg/kg methylprednisolone IV for at least several days until improved to grade ≤1, followed by at least 4-5 weeks of tapering doses. 1
• Add additional immunosuppressive agents in severe refractory cases. 1
• Provide supportive treatments including appropriate heart failure management. 1

Grade 3 (Moderate Abnormalities) Management

• Consider withholding immune checkpoint inhibitors. 1
• If confirmed cardiac injury or decompensation, hold therapy until stabilized. 1
• Consider corticosteroids if myocarditis is suspected. 1

Myositis Without Cardiac Involvement

For severe myositis (Grade 3-4) without cardiac involvement:

• Hold immune checkpoint inhibitors until Grade 1 or less while off immune suppression. 1
• Initiate prednisone 1 mg/kg or equivalent. 1
• Consider 1-2 mg/kg methylprednisolone IV or higher-dose bolus if severe compromise exists (weakness severely limiting mobility, respiratory compromise, dysphagia). 1
• Consider plasmapheresis or IVIG therapy. 1
• Approximately 10% of patients receive plasma exchanges, and up to 20% receive intravenous immunoglobulins. 1

Evidence on Corticosteroid Efficacy

Intravenous methylprednisolone followed by prednisone and immunosuppressive therapy appears effective for treating myocardial involvement in patients with idiopathic inflammatory myopathies, with cardiac MRI showing marked reduction in inflammation after 6 months of treatment. 2 However, for viral myocarditis specifically, corticosteroids do not reduce mortality and their benefit on cardiac function remains uncertain due to low-quality evidence. 4

Critical Consultation Requirement

Active, ongoing consultation with a cardiologist to discuss the risk/benefit of continuing immune checkpoint inhibitor therapy, starting corticosteroids, or instituting other cardiac treatments cannot be overstated. 1 This multidisciplinary approach is essential given the life-threatening nature of cardiac involvement and the complexity of treatment decisions.

Common Pitfalls to Avoid

• Never assume cardiac involvement is absent based solely on normal initial troponin levels. 1
• Do not delay cardiac evaluation in any patient with myositis, even if asymptomatic—two patients with dermatomyositis and overlap syndromes were asymptomatic yet had cardiac involvement on MRI. 2
• Recognize that myositis-associated autoantibodies are mostly negative in immune checkpoint inhibitor-related myositis, though some cases with positive ANA, antistriated antibodies, or other myositis-specific antibodies have been reported. 1
• Caution is advised with immune checkpoint inhibitor rechallenge after myositis with cardiac involvement. 1