By Van Selby, MD

Assistant Professor of Medicine, University of California, San Francisco Cardiology Division, Advanced Heart Failure Section

Dr. Selby reports no financial relationships relevant to this field of study.

SYNOPSIS: In patients with acute myocarditis and preserved left ventricular ejection fraction who underwent cardiac magnetic resonance, the presence of late gadolinium enhancement involving the midwall layer of the anteroseptum was associated with a worse prognosis.

SOURCE: Aquaro GD, Perfetti M, Camastra G, et al. Cardiac MR with late gadolinium enhancement in acute myocarditis with preserved systolic function: ITAMY study. J Am Coll Cardiol 2017;70:1977-1987.

Cardiac magnetic resonance (CMR) is used frequently in the evaluation of acute myocarditis (AM). In addition to its diagnostic utility, CMR also can help determine prognosis in AM. In particular, the presence of late gadolinium enhancement (LGE), a sign of myocardial scar, has been associated with worse patient outcomes. However, it is unknown whether all patterns of LGE observed in AM carry the same prognostic implications. Aquaro et al evaluated CMR results from 386 patients with confirmed AM and ejection fraction (EF) > 50% who were enrolled in the ITAlian multicenter study on Acute MYocarditis (ITAMY). Patients with heart failure, arrhythmias, or hemodynamic instability at the time of presentation were excluded. Patients were categorized based on the pattern of LGE observed on the baseline CMR. The primary endpoint was a composite of cardiac death, hospitalization for heart failure, resuscitated cardiac arrest, or appropriate implantable cardioverter-defibrillator firing. The median age was 35 years, and 95% of patients presented with chest pain. Four distinct LGE patterns were identified. One hundred fifty-four patients (41%) exhibited diffuse LGE throughout the subepicardial layer of the inferior and lateral segment. In 135 patients (36%), LGE was identified in the midwall of the anteroseptum (referred to as the AS group). Fifty-nine patients (15%) demonstrated LGE in other distributions, and 26 patients exhibited no LGE. Patients in the AS group showed larger ventricular volumes, higher peak troponin levels, and lower levels of inflammatory markers at presentation.

Over a median follow-up of 1,572 days, patients in the AS group received a worse prognosis compared to those in other groups (P < 0.0001). In a multivariable analysis, the presence of AS LGE was the strongest independent CMR predictor of the primary endpoint (odds ratio, 2.73; P = 0.01). The AS pattern also was associated with subsequent worsening of EF on follow-up studies. There were no significant differences in outcomes among the other three patient groups. The authors concluded that in patients with AM and preserved EF, LGE in the midwall layer of the anteroseptum is associated with a worse prognosis compared to other LGE patterns.

COMMENTARY

In acute myocarditis, both the clinical presentation and disease course are highly variable. Most patients in the Aquaro et al study presented with infarct-like AM, characterized by chest pain and ECG abnormalities. In cases of infarct-like AM with preserved EF, CMR is particularly sensitive for the detection of myocarditis and has become the diagnostic imaging modality of choice in these patients. In cases of myocarditis presenting with heart failure or arrhythmias, CMR is less sensitive and endomyocardial biopsy is used often.

Left ventricular EF is one of the strongest predictors of survival in AM, but some patients with normal EF still will proceed to adverse outcomes, including arrhythmia, heart failure, or death. LGE also is associated with worse outcomes, even in patients with preserved EF. Aquaro et al built on previous knowledge regarding predictors of adverse outcomes in AM. By looking at the specific pattern of LGE, clinicians can identify those patients with a poor prognosis despite normal EF at presentation. Approximately one-third of all patients presenting with AM and preserved EF demonstrated this AS pattern of LGE that places them at increased risk for adverse outcomes. Given the frequency with which CMR is obtained in these patients, it is important for clinicians to recognize this as a specifically high-risk pattern rather than just looking for the presence or absence of LGE. In fact, with the AS group excluded, survival was similar among those patients with and without LGE.

The major limitation of this study is the small sample size, with only 29 total events between the four groups. The patient population also was somewhat restricted, and the findings can be applied only to AM patients with normal EF and no evidence of heart failure, arrhythmia, or hemodynamic instability. However, the patients studied are the ones most likely to undergo CMR in clinical practice. The study is also limited by the lack of T1 and T2 mapping, which are used increasingly in the evaluation of AM patients.

It is not clear why one particular LGE pattern would be associated with worse outcomes. Compared to patients in other groups, those with AS generally exhibited more ventricular enlargement and higher troponin levels at presentation, despite lower levels of inflammatory markers. This suggests a difference in the underlying pathophysiology. A prior study of LGE patterns in AM found that AS generally was associated with human herpesvirus 6 infection, whereas the inferolateral pattern was seen in patients with parvovirus infections. While it is possible that different viral pathogens can explain the observed differences in outcome, Aquaro et al did not include viral testing and, therefore, cannot answer this question with any certainty.

Cardiac MR already is gaining acceptance as the diagnostic test of choice in patients with AM and no heart failure or arrhythmia. The study by Aquaro et al further solidifies the utility of CMR and provides a new high-risk feature that clinicians should look for when interpreting these studies.