**3.4 Biopsy**

While the gold standard for diagnosing myocarditis remains histopathological evidence via endomyocardial biopsy (EMB), the invasive nature of the procedure has made the alternative, often a clinical diagnosis (history, examination, labs, ECG)

**Figure 7.**

*Clinical and diagnostic approach to diagnosis of myocarditis.*

### *The Evaluation of Myocarditis in the Post-Covid-19 Era: Pearls and Perils for the Clinician DOI: http://dx.doi.org/10.5772/intechopen.110395*

along with echocardiogram and CMR much more common in practice. Biopsy is often reserved in cases of acute myocarditis due to its invasiveness but becomes particularly important in fulminant myocarditis. The initial clinical approach to diagnosis of myocarditis is illustrated in **Figure 7**. An EMB should be performed in the setting of unexplained acute cardiomyopathy (usually a dilated cardiomyopathy) and when other causes of cardiomyopathy have been excluded (ischemic, hypertensive/valvular, metabolic, toxic) in a patient that demonstrates symptoms of refractory heart failure not responding to guideline directed medical therapy, high grade heart block, symptomatic VT or requiring inotropic or mechanical circulatory support [74]. When there is adequate suspicion for giant cell myocarditis, a rare but important cause of cardiomyopathy, death, and transplant, EMB has shown an 82–85% sensitivity on diagnosis [75]. If diagnosed early, it can respond to calcineurin based treatment (cyclosporine) with positive outcomes on treatment course. In contrast, low-risk patients with more benign clinical presentations (hemodynamic stability, mild to normal LVEF >50%, without ventricular arrhythmias or heart block), CMR is preferred over EMB [49].

EMB has the potential for guiding therapy in patients with myocarditis or inflammatory related cardiomyopathies. These patients can be classified into four groups based on biopsy results (**Figure 8**): inflammation-negative, virus-negative; inflammation-positive, virus-negative; inflammation-negative, virus-positive; and inflammation-positive, virus-positive. In addition to guideline directed medical therapy for heart failure, immunosuppressive therapy should be a mainstay for virus-negative inflammatory cardiomyopathy [23]. It should be noted the potential relationship between an idiopathic dilated cardiomyopathy and various stages of myocarditis, thus, it is prudent to delineate the presence of residual inflammation or virus in such patients with a thorough investigation albeit myocardial biopsy and/ or advanced cardiac imaging, if clinically indicated. In addition, further research is

needed regarding the potential role that autoantibody targeting may have in autoimmune, or virus associated inflammatory heart disease.

### **4. Management/prognosis**

In line with the broad spectrum of etiologies, management of myocarditis includes conventional treatment for arrhythmias and heart failure along current guidelines [49, 76]. Tachy or bradyarrhythmia is common in the acute phase of myocarditis or can be asymptomatic. Antiarrhythmic therapy is generally reserved for symptomatic ventricular tachycardia or supraventricular tachycardias that can exacerbate underlying heart failure. Cardioversion can be considered for sustained ventricular arrhythmias. Implantable cardioverter (ICD) is indicated per guideline directed therapy for life threatening arrhythmias or persistent myocardial dysfunction.

Pharmacological treatment is the most common, first line approach including beta blockers for less than class IV heart failure, or the use of amiodarone, dofetilide in refractory cases. Patients that present with hemodynamic stability with sequelae of either acute or chronic heart failure should receive diuretics, angiotensin-converting– enzyme inhibitors, or angiotensin-receptor blockers and beta-adrenergic blockers if tolerable. Aldosterone antagonists may be added for more advanced heart failure with symptoms that persist or LVEF <35%.

The presentation of hemodynamically unstable heart failure may require mechanical circulatory support. In patients presenting with cardiogenic shock where there is severe ventricular systolic dysfunction refractory to medical therapy, ventricular assist devices or extracorporeal membrane oxygenation (ECMO) may be required to prevent multi-organ dysfunction and provide a bridge to recovery by allowing for myocardial recovery or transplant [77].

Patients with myocarditis are encouraged to avoid nonsteroidal anti-inflammatory drugs, alcohol consumption or other toxin mediated substances that have been shown to increase severity of myocarditis. Abstinence from heavy aerobic physical activity has been shown to reduce myocardial demand and reduce the potential for accelerating viral replication. Avoiding physical activity for a period of 3–6 months following the acute phase of myocarditis is recommended with reassessment every 6 months, including the use of repeat biopsy or advanced imaging such as CMR [49, 78].

Current ACC/AHA/ESC guidelines recommend consideration of immunosuppression for patients with active myocarditis and negative viral genome on EMB. A viral genome analysis is generally recommended on EMB samples to determine the safe use of immunosuppressants. Immunosuppressant regimen combinations that include glucocorticoids, azathioprine, cyclosporine is the basis for therapy for giant-cell myocarditis, cardiac sarcoidosis and eosinophilic myocarditis (once drugs or parasites have been ruled out). Patients with a positive viral biopsy for PVB19, HHV-6, CMV, Epstein-Barr, should have initial treatment with antiviral therapy during the acute phase then maintenance with immunosuppression. Ongoing, future, studies for alternative regimens include: the Myocarditis Therapy with Steroids [MYTHS] trial, Anakinra versus Placebo for the Treatment of Acute Myocarditis [ARAMIS], Abatacept for the Treatment of Immune-Checkpoint Inhibitors Induced Myocarditis [ACHLYS].

*The Evaluation of Myocarditis in the Post-Covid-19 Era: Pearls and Perils for the Clinician DOI: http://dx.doi.org/10.5772/intechopen.110395*
