Table 3.

Different modalities for diagnosing ICI-associated myocarditis, as proposed by Bonaca et al. (unpublished results)

Modality	Tissue pathology on biopsy or autopsy (gold standard)	cMRI	New WMA on echocardiogram	New elevated biomarker beyond baseline
Definite myocarditis is any of:	Pathology sufficient	cMRI plus: Syndrome AND (Biomarker OR ECG)	WMA plus: Syndrome AND Biomarker AND ECG AND negative angiography
Probable myocarditis is any of:		cMRI without syndrome, biomarker, or ECG Non-diagnostic CMR plus: Syndrome OR Biomarker OR ECG	WMA plus: Syndrome AND (Biomarker OR ECG)
Possible myocarditis is any of:		Non-diagnostic cMRI without syndrome, biomarker, or ECG	WMA plus: Syndrome OR ECG	Biomarker plus: Syndrome OR ECG

Myocarditis can be diagnosed by one of several modalities, in decreasing order of superiority: tissue pathology on biopsy or autopsy; cMRI; echocardiogram showing new WMA; or elevated biomarkers. In each of these modalities, positive findings must be supported with a combination of objective laboratory findings, physical exam, and pertinent history. Tissue pathology diagnostic of myocarditis is the gold standard and, by itself, establishes a diagnosis of definite myocarditis.

cMRI positive for myocarditis is considered definite myocarditis if accompanied by biomarker elevations and positive ECG findings. If positive cMRI is accompanied by neither physical exam and history findings, biomarker elevations, nor ECG findings, the diagnosis is probable myocarditis. If cMRI is suggestive of myocarditis but non-diagnostic, the diagnosis can still be probable myocarditis if there are physical exam and history findings, elevated biomarkers, or ECG findings. On the other hand, if the non-diagnostic suggestive cMRI is accompanied by none of these, the diagnosis would be limited to possible myocarditis.

Using echocardiography, new WMA not explained by another diagnosis is considered definite myocarditis if it is accompanied by physical exam and history findings, elevated biomarkers, ECG findings, and negative angiography or other testing to exclude coronary artery disease. New WMA with physical exam and history findings and either elevated biomarkers or ECG findings are consistent with probable myocarditis. New WMA with either physical exam and history findings or ECG findings is consistent with possible myocarditis. If biomarkers are the lone studies available and positive, the diagnosis of possible myocarditis can still be made if there are physical exam and history findings and ECG findings.

cMRI, cardiac magnetic resonance imaging; WMA, wall motion abnormality.