Viral Myocarditis: Classification, Diagnosis, and Clinical Implications

Abstract

Myocarditis is an inflammatory disease of the myocardium with focal or diffuse involvement. Viral infections are the most common cause of myocarditis, especially in Western countries. A recent viral illness with gastroenteric or upper respiratory symptoms often precedes myocarditis. The absence of specific pathognomonic features in conjunction with the wide spectrum of clinical manifestations that range from subclinical cases to sudden cardiac death (SCD) makes myocarditis diagnosis particularly challenging. Moreover, myocarditis might represent a cause of initially unexplained dilated cardiomyopathy (DCM) and heart failure (HF), especially among children and young adults. Cardiac magnetic resonance imaging (CMR) is crucial for myocarditis diagnosis, because of its ability to detect interstitial edema during acute inflammation. Assessment of subepicardial or mid-myocardial fibrosis by late gadolinium enhancement (LGE) is typical for myocarditis. Cardiac arrhythmias are frequent events that may arise especially in more severe myocarditis cases. The most common form of arrhythmia is atrial fibrillation, followed by ventricular tachycardia. Documented arrhythmias have been reported more commonly with HIV myocarditis than other more common infections such as Adenovirus, Parvovirus B19, human Herpes virus 6, and Enterovirus. The mechanisms of arrhythmogenesis in myocardial inflammation are not fully understood; in the acute phase, the spectrum of arrhythmogenesis ranges from a direct effect on cardiomyocytes that leads to electrical instability and ion channel impairment to ischemia from coronary macro- or microvascular disease. In chronic myocarditis, instead, myocardial replacement with fibrosis promotes scar-mediated re-entrant ventricular arrhythmias. Observational data suggested the important role of CMR, with LGE being the strongest independent predictor of SCD, cardiac, and all-cause mortality. In acute myocarditis, the most common localization of subepicardial LGE dwells in the lateral wall. Patients with myocarditis that develop HF and arrhythmias usually show a larger LGE distribution involving several myocardial segments. Moreover, a mid-layer LGE in the interventricular septum is more frequent in acute myocarditis than in acute coronary syndromes cases. The risk of SCD in patients with wide areas of LGE is significant, and a shared decision-making approach is warranted. Nevertheless, there is no formal consensus about the extension of LGE to justify implantable cardioverter defibrillator (ICD) implantation in primary prevention.

Keywords: ICD (implantable cardioverter-defibrillator); arrhythmias; cardiac magnetic resonance; sudden cardiac arrest (SCA); viral myocarditis.

FIGURE 1

Three-phase model for the pathogenesis of myocarditis.

FIGURE 2

Case of acute myocarditis. (A,B) T1 and T2 mapping show increased value of both parameters in the lateral wall compatible with myocardial edema. (C,D) Four-chamber and short-axis views showing subepicardial late gadolinium enhancement (LGE) with typical pattern in the infero-lateral wall.

FIGURE 3

Case of a 50 y/o male with low-risk profile hospitalized for chest pain. (A) ECG pattern during chest pain showing PR-depression with diffuse ST-elevation. The coronary angiography was negative for significant lesions. (B–D) T1 mapping shows diffuse increased value more evident in the anterior and lateral wall, compatible with myocardial edema (4-chamber, 2-chamber, and short-axis views). (E–G) Extensive subepicardial LGE in the infero-lateral and in the antero-septal wall (4-chamber, 2-chamber, and short-axis views).

FIGURE 4

T1 mapping of the left ventricle 16 segment-model polar map comparing a normal case (left panel) and a case with higher T1 in the inferior wall due to inflammatory process (right panel).