Review of Myocarditis

Basso C.
Myocarditis. N Engl J Med 2022;387:1488-1500.

The following are key points to remember from this review of myocarditis, which focuses on epidemiology, causes and pathogenesis, clinical presentation, diagnosis, and therapy:

  1. Myocarditis is an inflammatory disease of the myocardium that is diagnosed on the basis of established histologic, immunologic, and immunohistochemical criteria. Myocarditis can result from a wide range of infectious or noninfectious causes, such as viruses, immune-system activation (autoimmunity [e.g., in sarcoidosis] or immune stimulation [e.g., vaccines or cancer therapies]), or exposure to toxins and drugs, including endogenous biochemical compounds, as seen in amyloidosis and in thyrotoxicosis.
  2. In the context of COVID-19, the mechanisms of cardiac injury are likely to be multifactorial and may include not only endothelialitis or myocarditis but also myocardial injury due to a mismatch between oxygen supply and demand, microvascular thrombosis, a systemic hyperinflammatory response, and myocardial ischemia.
  3. The role of genetics as a contributing factor in myocarditis is now documented, with putatively deleterious variants in genes related to cardiomyocyte structure and function detected in up to 16% of cases.
  4. The main clinical manifestations of myocarditis are chest pain with an otherwise uncomplicated clinical picture (preserved left ventricular ejection fraction [LVEF] and no ventricular arrhythmias), new or worsening heart failure, chronic heart failure, life-threatening hemodynamic compromise (i.e., fulminant myocarditis, with cardiogenic shock and severely impaired left ventricular function), and life-threatening arrhythmia or conduction disturbances (e.g., sustained ventricular arrhythmias, atrioventricular [AV] block, and sudden death).
  5. Giant-cell myocarditis should always be suspected in patients presenting with rapidly progressive heart failure or cardiogenic shock, with or without conduction disturbances, that does not respond to usual therapy.
  6. A noninvasive diagnostic workup helps to establish a diagnosis of “clinically suspected myocarditis,” on the basis of the clinical presentation and criteria in four categories: laboratory testing; electrocardiography, Holter monitoring, and stress testing; functional and structural assessment on cardiac imaging (echocardiography, angiography, and magnetic resonance imaging [MRI]); and tissue characterization on cardiac MRI. Cardiac MRI is a valuable tool and has the highest sensitivity if performed within 2-3 weeks after the initial clinical presentation.
  7. Endomyocardial biopsy can be reserved for patients with clinically suspected myocarditis and the following findings: cardiogenic shock or acute heart failure requiring inotropic or mechanical circulatory support; ventricular arrhythmias or Mobitz type II second-degree or higher AV block, particularly when symptom onset is recent, with mild or no left ventricular dilatation; peripheral eosinophilia or an associated systemic inflammatory disorder; persistent or recurrent release of necrosis markers, particularly when an autoimmune condition is likely or ventricular arrhythmias and high-degree AV block are present; or cardiac dysfunction in a patient receiving immune checkpoint inhibitor therapy.
  8. Treatment for myocarditis comprises management of arrhythmias and heart failure according to conventional guidelines and cause-targeted therapy.
  9. Early administration of immunosuppressive drugs (i.e., glucocorticoids alone or together with azathioprine, cyclosporine, or both) is the key therapy for eosinophilic myocarditis, as well as for giant-cell myocarditis and cardiac sarcoidosis. No specific therapy is available for lymphocytic acute myocarditis, except for the forms associated with systemic diseases and immune checkpoint inhibitors.
  10. Ongoing clinical trials are assessing the role of high-dose methylprednisolone in patients with acute myocarditis complicated by heart failure or cardiogenic shock (the Myocarditis Therapy with Steroids [MYTHS] trial); of anakinra, an interleukin-1 receptor antagonist (Anakinra versus Placebo for the Treatment of Acute Myocarditis [ARAMIS]), excluding patients with a hemodynamically unstable condition; and of abatacept (a CTLA-4–directed fragment aimed at blocking T-cell costimulation by CD80 or CD86) for the treatment of immune checkpoint inhibitor–induced myocarditis (Abatacept for the Treatment of Immune-Checkpoint Inhibitors Induced Myocarditis [ACHLYS]) and may provide additional therapeutic options.

Clinical Topics: Arrhythmias and Clinical EP, Cardio-Oncology, COVID-19 Hub, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Implantable Devices, EP Basic Science, Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Interventions and Imaging, Angiography, Echocardiography/Ultrasound, Magnetic Resonance Imaging, Nuclear Imaging

Keywords: Amyloidosis, Angiography, Arrhythmias, Cardiac, Atrioventricular Block, Autoimmunity, Cardiotoxicity, Chest Pain, COVID-19, Death, Sudden, Diagnostic Imaging, Echocardiography, Electrocardiography, Ambulatory, Endothelium, Genetics, Glucocorticoids, Heart Failure, Immune Checkpoint Inhibitors, Inflammation, Magnetic Resonance Imaging, Myocardial Ischemia, Myocarditis, Secondary Prevention, Shock, Cardiogenic, Steroids, Thrombosis, Thyrotoxicosis, Vaccines, Ventricular Function, Left, Viruses

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