T1 Value on Cardiac MRI Diagnoses Myocarditis Associated with Checkpoint Inhibitors
Key findings
- In this retrospective international study, cardiovascular magnetic resonance images of 136 patients with checkpoint inhibitor–associated myocarditis were evaluated according to the modified Lake Louise criteria
- Myocardial T1 and T2 values were significantly elevated in 78% and 43% of patients, respectively; patients with abnormal T1 values were more symptomatic and had lower cardiac function than those with normal T1 values
- During follow-up, higher T1 values, but not T2 values, were independently associated with major adverse cardiac events (HR=1.44 for every one-unit increase in T1 z-score; P=0.004)
- The team has developed an algorithm to help physicians determine whether ICI myocarditis is confirmed, likely or unlikely based on cardiovascular magnetic resonance findings
Myocarditis is an uncommon side effect of immune checkpoint inhibitor (ICI) therapy. However, myocarditis with an ICI can lead to substantial morbidity and mortality where 30% to 40% of patients develop major adverse cardiac events (MACE) and the case-fatality rate is up to 25%.
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The standard for noninvasive diagnosis of non-ICI myocarditis is cardiovascular magnetic resonance (CMR), interpreted according to the Lake Louise criteria. But as previously reported in the European Heart Journal, a team of Massachusetts General Hospital researchers and other members of an international study team discovered components of the original Lake Louise criteria are not universally present on CMR scans of patients with ICI myocarditis.
More recently the team applied the modified Lake Louise criteria, published in 2018, which incorporate parametric mapping techniques. Tomas G. Neilan, MD, MPH, co-director of the Cardiovascular Imaging Research Center and director of the Cardio-Oncology Program in the Corrigan Minehan Heart Center at Massachusetts General Hospital, and colleagues report in the Journal of the American College of Cardiology that elevated T1 values had robust diagnostic and prognostic value in patients with ICI myocarditis.
Study Methods
The researchers identified 136 patients in an international registry who had CMR images with T1 or T2 mapping data available: 86 had T1 maps and 79 had both T1 and T2 maps. These patients had been diagnosed with ICI myocarditis by histopathology or application of European Society of Cardiology criteria.
The two main criteria for diagnosing myocarditis according to the updated Lake Louise criteria are myocardial edema (based on T2 maps) and nonischemic myocardial injury (based on T1 maps).
T1/T2 Values and ICI Myocarditis
Native T1 and T2 values were higher than reference values in this cohort regardless of the CMR vendor or field strength. T1 values were significantly elevated in 78% of patients and T2 values in 43%.
Patients with abnormal T1 values were more symptomatic and had lower cardiac function than those with normal values. They were more likely to have paroxysmal nocturnal dyspnea and peripheral edema, and they had lower left ventricular ejection fraction at diagnosis and during a hospital stay.
Lake Louise Criteria and ICI Myocarditis
The modified Lake Louise criteria were applied to the 79 patients with both T1 and T2 maps. 95% of patients met the nonischemic myocardial injury criteria, 53% met the myocardial edema criteria, and 48% met both criteria. 100% met at least one of the criteria.
MACE and T1/T2 Values
Over a median follow-up of 158 days, 31% of patients developed MACE, defined as the composite of cardiovascular death, cardiac arrest, cardiogenic shock and complete heart block requiring a pacemaker. MACE occurred in:
- 0% of patients with normal T1 values vs. 40% of those with abnormal values (P<0.001)
- 20% of patients with normal T2 values and 42% of those with abnormal values (P=0.03)
T1 values, but not T2 values, had excellent discriminatory and prognostic value for subsequent MACE:
- The area under the curve for T1 values, 0.91
- HR, 1.44 for every one-unit increase in T1 z-score (P=0.004) after adjustment for relevant covariates and presence of late gadolinium enhancement
A Preliminary Algorithm
The researchers include an algorithm in their paper designed to help physicians determine whether ICI myocarditis is confirmed, likely or unlikely based on CMR findings. They note it should be considered preliminary until this study is validated.
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