Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor–Associated Myocarditis

Q: What are the key findings of this study?

Higher native myocardial T1 values were independently associated with an increased risk of major adverse cardiovascular events (HR 1.44 per 1-unit increase in z-score) in patients with ICI myocarditis.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Immune checkpoint inhibitor (ICI) associated myocarditis (n=86). Intervention: Native T1 mapping (z-score) vs. Lower T1 z-score. Primary outcome: Major adverse cardiovascular events (MACE) (HR 1.44, 95% CI 1.12-1.84, p=0.004).

Q: What does this research mean for the field?

Elevated native T1 mapping values on cardiovascular magnetic resonance are independently associated with subsequent major adverse cardiovascular events in patients with immune checkpoint inhibitor-associated myocarditis. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Paaladinesh Thavendiranathan; Lili Zhang; Amna Zafar; Zsófia D. Drobni; Syed Mahmood; Marcella Cabral; Magid Awadalla; Anju Nohria; Daniel A. Zlotoff; Franck Thuny; Lucie Heinzerling; Ana Barac; Ryan J. Sullivan; Carol L. Chen; Dipti Gupta; Michael Constantin Kirchberger; Sarah Hartmann; Jonathan W. Weinsaft; Hannah Gilman; Muhammad A. Rizvi; Bojan Kovacina; Caroline Michel; Gagan Sahni; Ana González‐Mansilla; Antonio Calles; Francisco Fernández‐Avilés; Michael Mahmoudi; Kerry L. Reynolds; Sarju Ganatra; Juán José Gavira; Nahikari Salterain González; M. Castro; Raymond Y. Kwong; Michael Jerosch‐Herold; Otávio R. Coelho‐Filho; Jonathan Afilalo; Eduardo Zatarain‐Nicolás; A. John Baksi; Bernd J. Wintersperger; Oscar Calvillo‐Argüelles; Stéphane Éderhy; Alexander R Lyon; Michael G. Fradley; Tomas G. Neilan

doi:10.1016/j.jacc.2021.01.050

March 1, 2021Journal of the American College of CardiologyOpen Access

Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor–Associated Myocarditis

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Key result

Higher native T1 linked to ~44% higher MACE risk per z-score in ICI myocarditis.

HR 1.44
95% CI 1.12-1.84
P=0.004
n=86

Why the study?

Myocarditis is a potentially fatal complication of ICI therapy, but data on the utility of CMR T1 and T2 mapping in ICI myocarditis are limited.

Does cardiovascular magnetic resonance T1 and T2 mapping provide diagnostic and prognostic value in patients with immune checkpoint inhibitor-associated myocarditis?

Key Points

To evaluate the diagnostic and prognostic utility of cardiovascular magnetic resonance (CMR) native T1 and T2 mapping in patients with immune checkpoint inhibitor (ICI)–associated myocarditis.
Retrospective registry study analyzing clinical and CMR mapping data from 136 patients with ICI myocarditis, of whom 86 had T1 maps and 79 had both T1 and T2 maps.
Abnormal T1 and T2 values were defined as >2 standard deviations above vendor- and field-strength–specific normal reference values, with z-scores calculated for each patient.
The primary endpoint was major adverse cardiovascular events (MACE), a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block over a median follow-up of 158 days.
Abnormal native T1 and T2 values were present in 78% and 43% of patients, respectively; 95% met the modified Lake Louise non-ischemic myocardial injury criteria and 53% met myocardial edema criteria.
Overall MACE occurred in 31.4% of patients (27/86), with event rates of 0.0% in patients with normal T1 values versus 40.3% in those with abnormal T1 values (p<0.001).

Study Design

Type

Cohort (n=86)

Multicenter

Yes

Structured PICO

Does cardiovascular magnetic resonance T1 and T2 mapping provide diagnostic and prognostic value in patients with immune checkpoint inhibitor-associated myocarditis?

P

Population

86 patients with immune checkpoint inhibitor-associated myocarditis who underwent cardiovascular magnetic resonance with T1 mapping, followed for a median of 158 days.

E

Exposure

Cardiovascular magnetic resonance (CMR) T1 and T2 mapping

O

Outcome

Major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart blockcomposite

Main Result

Hazard Ratio: 1.44 (95% CI 1.12–1.84)

p-value: p=0.004

Limitations

Retrospective multi-center study with non-pre-specified CMR protocol, different magnet strengths, and local site reads
Single short-axis slice used to measure T1 and T2 values
Majority of patients received corticosteroids prior to their CMR study, which may have affected edema/inflammation
Limited statistical power due to sample size
Lack of patients without ICI myocarditis for comparison to calculate diagnostic sensitivity/specificity
Retrospective multi-center study with non-pre-specified CMR protocols, different magnet strengths, and local site reads
Majority of patients received corticosteroids prior to their CMR study
Limited statistical power
Lack of patients with negative biopsies to allow calculation of sensitivity/specificity for T1 and T2 mapping

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

In patients with ICI myocarditis, CMR native T1 mapping provides important diagnostic value and is independently associated with subsequent major adverse cardiovascular events.

Abstract

Background: Myocarditis is a potentially fatal complication of ICI therapy. Data on the utility of CMR T1/T2 mapping in ICI myocarditis are limited. Objectives: To assess the value of cardiovascular magnetic resonance (CMR) T1/T2 mapping in patients with immune checkpoint inhibitor (ICI) associated myocarditis. Methods: In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1/T2 maps) were collected. Abnormal T1/T2 were defined as 2 standard deviations (SD) above site (vendor/field-strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. Results: Of 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) had T2 maps. Among the 86 patients (66.3±13.1 years), 36 (41.9%) had an LVEF <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9±1.9 (p<0.001) and 2.2±2.1 (p<0.001) respectively. On Siemens 1.5T (n=67), native T1 (1079.0±55.5 vs. 1000.3±22.1ms, p<0.001) and T2 (56.2±4.9 vs. 49.8±2.2ms, p<0.001) values were elevated compared to reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louse Criteria, 95% met the “non-ischemic myocardial injury” criteria and 53% met the “myocardial edema” criteria. Native T1 values had excellent discriminatory value for subsequent MACE with an AUC of 0.91 (95% CI 0.84–0.98). Native T1 values (HR 1.44, 95% CI 1.12, 1.84, for every 1 unit increase in z-score, p=0.004), but not T2 values were independently associated with subsequent MACE. Conclusions: The use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis.

Discussion

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Cite This Study

Thavendiranathan et al. (2021) conducted a cohort in Immune checkpoint inhibitor (ICI) associated myocarditis (n=86). Native T1 mapping (z-score) vs. Lower T1 z-score was evaluated on Major adverse cardiovascular events (MACE) (HR 1.44, 95% CI 1.12-1.84, p=0.004). Higher native myocardial T1 values were independently associated with an increased risk of major adverse cardiovascular events (HR 1.44 per 1-unit increase in z-score) in patients with ICI myocarditis.

synapsesocial.com/papers/6a7f31e3acee79676f45076a https://doi.org/10.1016/j.jacc.2021.01.050

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Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor–Associated Myocarditis

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor–Associated Myocarditis

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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