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on the role of sex in the prognosis of IMPS.73 Women seem to have a more favourable prognosis than men in myocarditis.338 Young age and a previous myocarditis were independent relapse predictors. Fulminant onset, lower LVEF at presentation, distinct autoimmune features, especially in women, and high-titre organ-specific anti-heart autoantibodies and antinuclear autoantibodies were independent predictors of death and HT.73 Genetic predisposition may also increase the risk (see Section 5.3). The aetiology also plays a relevant role, e.g. EM, GCM and CS are associated with a worse prognosis (Sections 9.2–9.4). Outcomes are worse in patients with FM, in the case of late diagnosis and delayed interventions.57 Factors associated with increased mortality or HT are GCM, QRS duration of >120 ms on initial ECG, or the need for temporary MCS other than IABP.56 Biventricular dysfunction has been described as the main predictor of death or HT in myocarditis.63,66,73 Multimodality imaging contributes to the assessment of prognosis. For example, myocarditis patients with normal CMR have a good prognosis.339 Late gadolinium enhancement on CMR at initial presentation is an important prognostic finding.340 In a multicentre study with AM and preserved EF, the presence of anteroseptal LGE in the mid-wall layer was the best independent predictor of the combined endpoint of cardiac death, appropriate ICD interventions, resuscitated cardiac arrest, and hospitalization for HF [odds ratio (OR) 2.73; 95% confidence interval (CI) 1.2–5.9; P = .01]. At a median follow-up of 4.3 years, 7.7% of these patients reached the combined endpoint.3 Anteroseptal LGE was the best independent predictor of SCD [hazard ratio (HR) 4.59; 95% CI 1.38–15.24; P = .01]. Myocardial fibrosis was present in 95% of patients with SCD, compared with 41% in patients without SCD.341 Additionally, major arrhythmic onset (sustained VT or VF), presence of fibrosis at EMB, and induction of major VA on PVS all predicted major arrhythmic events.63,73,255 In another study, including patients with AM and life-threatening arrhythmias, positive LGE in two or more myocardial segments and absence of oedema on initial CMR were associated with an increased risk for recurrent major arrhythmic events, including SCD [HR 4.51 (95% CI 2.39–8.53) and HR 2.59 (95% CI 1.40–4.79), respectively].71 Large studies are needed in the future to develop a risk stratification with a high negative predictive value for SCD and the need for ICD implantation. Variables for risk stratification for the progression to DCM are given in Supplementary data online, Table S9.

7.1.1 Sequela and mortality in myocarditis

The main long-term complications are evolution to DCM with subsequent HF and (recurrence of) VA, including SCD.76 LVEF recovery after myocarditis can be complete or partial. Recovery rates vary from 50% to 94% depending on the initial presentation.74 These patients usually have a gradual deterioration of LVEF and subsequent dilation and might remain unrecognized and asymptomatic until development of overt HF. Myocarditis can cause about 10% of DCM.66 Patients with B19V AM present most often with an infarct-like syndrome, and may have a favourable long-term prognosis,342 but there is evidence describing cases with severe fatal outcomes.228 In contrast, patients with HHV-6 myocarditis (and especially those with B19V and HHV-6 co-infection) usually present with acute HF symptoms, and frequently progress to chronic HF.342

Arrhythmias during myocarditis range from mild conduction abnormalities to life-threatening VT or VF, requiring medication and/ or device therapy (refer to Section 6.5). The risk of VA is independent of LVEF.83,343 Myocarditis may have a significant mortality. Initial complicated presentation and histological subtype predict the risk. Outcomes are worse in patients with FM, with a reported mortality at 60 days of 24%.56,73 Mortality also depends on the underlying cause of FM. In a study of GCM survivors beyond 1 year, the combined rate of death, HT, VAD implantation, or GCM recurrence was 47% at 5 years.344 Reported in-hospital mortality and long-term outcomes after an episode of AM vary.345 In a multicentre registry of patients with AM, complicated AM occurred in 27%, including 9% cases of FM. In-hospital mortality was 8.5%, compared with 0% in uncomplicated cases. Heart transplantation or LVAD was required in 3% and 4% of patients, respectively. Heart transplantation or death occurred in 18% of complicated cases after 5 years. Recurrences or VA occurred in approximately 3%–9% of cases over a period of 19–90 months.28 In the recently reported contemporary ESC multicentre myocarditis registry of 581 patients with myocarditis, 2.7% of patients died, 1.7% received a HT, 0.7% underwent VAD implantation, and 3.9% underwent ICD implantation at 1-year follow-up.62,63,73

7.1.2 Follow-up

Patients with low-risk myocarditis with chest pain presentation can be discharged when cardiac enzymes tend towards normalization. Time to recovery in AM varies from a few days to a few months. Relapses occur in about 10% of cases, with a 1-year recurrence rate of around 5%.10,73,346 Follow-up is recommended in all patients with myocarditis, with clinical assessment, ECG, Holter-ECG registration, exercise test (if no signs of ongoing inflammation), echocardiography, and CMR within at least 6 months after the index hospitalization (see Table 15).10,62 The prognosis is determined by baseline and 6-month LV function, regardless of the initial clinical presentation.62,63,73 Cardiovascular magnetic resonance should be performed at least within the first 6 months in patients with definite myocarditis to guide the timepoint for return to work, based on the individual case. It is generally accepted to wait 3–6 months after an acute episode of myocarditis to evaluate the need for an ICD. In some patients at high risk for VA (see Section 6.5.1),71 a WCD should be considered during follow-up as a bridge to recovery.58 Subsequently, after 3–6 months of follow-up, the decision on whether or not to implant a definitive ICD is based on the individual patient, with increasing indication based on risk factors including genetic predisposition (see Section 5.3, Section 6.5.1; see Figure 17). In patients presenting with symptomatic VA, or heart block in GCM or CS, early consideration of an ICD is warranted.58 Recommendations concerning arrhythmias and SCD in specific forms of myocarditis are discussed in Section 6.5.58 In uncomplicated cases, a follow-up at 6, 12, and 24 months is sufficient, while it should be prolonged and be lifelong in complicated cases or with residuals. See Supplementary data online, Section 8 for patient communication advice.

ESC Guidelines                                                                                                                                                                                          3997

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