Prognostic Value of Cardiac Magnetic Resonance Tissue Characterization in Risk Stratifying Patients With Suspected Myocarditis

Gräni, Christoph; Eichhorn, Christian; Bière, Loïc; Murthy, Venkatesh L.; Agarwal, Vikram; Kaneko, Kensuke; Cuddy, Sarah; Aghayev, Ayaz; Steigner, Michael L.; Blankstein, Ron; Jerosch‐Herold, Michael; Kwong, Raymond Y.

doi:10.1016/j.jacc.2017.08.050

Cited by 344 publications

(314 citation statements)

References 34 publications

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“…The major cardiac event rate of almost 50% was markedly increased compared with cases of myocarditis in broad populations. For example, among 670 patients admitted to hospital with myocarditis unrelated to ICI, a fulminant course was noted in 15% of patients (29,30). An additional difference is that, in our cohort, 38% of patients who had a fulminant course had a normal LVEF.…”

Section: Discussionmentioning

confidence: 99%

Myocarditis in Patients Treated With Immune Checkpoint Inhibitors

Mahmood

Fradley

Cohen

et al. 2018

Journal of the American College of Cardiology

1,151

1,202

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BACKGROUND Myocarditis is an uncommon, but potentially fatal, toxicity of immune checkpoint inhibitors (ICI). Myocarditis after ICI has not been well characterized. OBJECTIVES The authors sought to understand the presentation and clinical course of ICI-associated myocarditis. METHODS After observation of sporadic ICI-associated myocarditis cases, the authors created a multicenter registry with 8 sites. From November 2013 to July 2017, there were 35 patients with ICI-associated myocarditis, who were compared to a random sample of 105 ICI-treated patients without myocarditis. Covariates of interest were extracted from medical records including the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically significant complete heart block. RESULTS The prevalence of myocarditis was 1.14% with a median time of onset of 34 days after starting ICI (inter-quartile range: 21 to 75 days). Cases were 65 ± 13 years of age, 29% were female, and 54% had no other immune-related side effects. Relative to controls, combination ICI (34% vs. 2%; p < 0.001) and diabetes (34% vs. 13%; p = 0.01) were more common in cases. Over 102 days (interquartile range: 62 to 214 days) of median follow-up, 16 (46%) developed MACE; 38% of MACE occurred with normal ejection fraction. There was a 4-fold increased risk of MACE with troponin T of ≥1.5 ng/ml (hazard ratio: 4.0; 95% confidence interval: 1.5 to 10.9; p = 0.003). Steroids were administered in 89%, and lower steroids doses were associated with higher residual troponin and higher MACE rates. CONCLUSIONS Myocarditis after ICI therapy may be more common than appreciated, occurs early after starting treatment, has a malignant course, and responds to higher steroid doses.

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Section: Discussionmentioning

confidence: 99%

Myocarditis in Patients Treated With Immune Checkpoint Inhibitors

Mahmood

Fradley

Cohen

et al. 2018

Journal of the American College of Cardiology

1,151

1,202

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“…A combination of these CMR criteria has a sensitivity of 76% and specificity of 96% for myocarditis . CMR has also shown to be an effective tool for risk stratification and prognostication in general cases of myocarditis . Despite the potential benefits of CMR, its limited availability and the difficulty in obtaining this relatively lengthy test in severely ill patients are major obstacles that restrict its widespread use in every patient with suspected myocarditis.…”

Section: Managementmentioning

confidence: 99%

Immune Checkpoint Inhibitor-Associated Myocarditis

2018

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Immune checkpoint inhibitors (ICIs) are approved for a wide range of malignancies. They work by priming the immune system response to cancer and have changed the landscape of available cancer treatments. As anticipated, modulation of the regulatory controls in the immune system with ICIs results in diverse immune-related adverse events, targeting any organ or gland. These toxicities are rarely fatal and generally regress after treatment discontinuation and/or prescription of corticosteroids. Recently, several cases of ICI-related cardiotoxicity have been reported with complications ranging from cardiogenic shock to sudden death. The true incidence of ICI-associated myocarditis is likely underestimated, due to a combination of factors including the lack of specificity in the clinical presentation, the potential of overlap with other cardiovascular and general medical illnesses, the challenges in the diagnosis, and a general lack of awareness of this condition. Currently, there are no clear guidelines for surveillance, diagnosis, or management of this entity. There are multiple unresolved issues including, but not limited to, identifying those at risk of this uncommon toxicity, elucidating the pathophysiology, determining if and what type of surveillance is appropriate, optimal work-up of suspected patients, and methods for resolution of myocarditis. Here we describe a clinical vignette and discuss the salient features and management strategies of ICI-associated myocarditis. The Oncologist 2018;23:518-523 KEY POINTS• The incidence of immune checkpoint inhibitor (ICI)-associated myocarditis is unclear and has been reported to range from 0.06% to 1% of patients prescribed an ICI.• Myocarditis may be difficult to diagnose.• The risk factors for ICI-associated myocarditis are not well understood but may include underlying autoimmune disease and diabetes mellitus. • The prevalence of myocarditis has been reported to be higher with combination immune therapies.• Myocarditis with ICI's typically occurs early, with an elevated troponin, may present with an normal left ventricular ejection fraction and may have a fulminant course.• The optimal management of myocarditis associated with ICI's is unclear but most cases are treated with high-dose steroids. PATIENT STORYA 41-year-old woman with no cardiac risk factors but a prior history of Hashimoto's thyroiditis was diagnosed with metastatic melanoma. She presented with mild dyspnea 6 days after completing four cycles of combined immune checkpoint inhibitor (ICI) therapy with ipilimumab and nivolumab. On exam, she was tachycardic and mildly volume overloaded but was otherwise stable. Sinus tachycardia was noted on electrocardiogram (ECG); there were no conduction abnormalities (Fig. 1A). Cardiac troponin I (cTn) was mildly elevated with normal level of N-terminal-pro brain natriuretic peptide (NT-proBNP). A chest computed tomography (CT) scan did not show evidence of pneumonitis but did show cardiomegaly and pulmonary congestion. An echocardiogram revealed global left...

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“…Recent studies have demonstrated the prognosis in the individual diagnostic categories like myocarditis and Takotsubo cardiomyopathy. (19)(20)(21) However, there is no evidence in the literature on the prognostic significance of the CMR findings and conventional risk factors in MINOCA. The only study which looked at mid-term mortality was by Mittal et al (22) However, they looked at patients presenting via the primary percutaneous coronary angiography pathway with non-obstructed coronaries.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Role of CMR and Conventional Risk Factors in Myocardial Infarction With Nonobstructed Coronary Arteries

Dastidar

Baritussio

Gárate

et al. 2019

JACC: Cardiovascular Imaging

173

105

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Word count: 4478words (including figures legends and references)Running title: Prognostic role of CMR and conventional risk factors in MINOCA Abstract: Objective: Assess the prognostic impact of Cardiovascular Magnetic Resonance (CMR) and conventional risk factors in patients with Myocardial infarction with non-obstructed coronaries (MINOCA). Background: MINOCA represents a diagnostic dilemma and the prognostic markers have not been clarified. Methods: 388 consecutive MINOCA patients undergoing CMR assessment were identified retrospectively from registry database and prospectively followed up for a primary clinical endpoint of all-cause mortality. 1.5T CMR was performed using a comprehensive protocol (cines, T2-weighted, and late gadolinium enhancement sequences). Patients were grouped into 4 categories based on their CMR findings: myocardial infarction (MI) (embolic/spontaneous recanalization), myocarditis, cardiomyopathy and normal CMR. Results: CMR(performed at a median of 37days from presentation) was able to identify the cause for the troponin rise in 74% of the patients (25% myocarditis, 25% MI and 25% cardiomyopathy), whilst a normal CMR was identified in 26%. Over a median follow-up of 1262days(3.5years), 5.7% patients died. Cardiomyopathy group had the worst prognosis (mortality 15%, log rank 19.9 p<0.001), MI had 4% mortality, and 2% in both myocarditis and normal CMR. In a multivariable cox regression model (including clinical and CMR parameters), CMR diagnosis of cardiomyopathy and ST-segment elevation on presentation ECG remained the only 2 significant predictors of mortality. Using presentation with ECG ST-elevation and CMR diagnosis of cardiomyopathy as risk markers, the mortality risk rates were 2%, 11% and 21% for presence of 0, 1 and 2 factor respectively(p<0.0001). Conclusion: In a large cohort of MINOCA, CMR(median 37days from presentation) identified a final diagnosis in 74% of patients. Cardiomyopathy had the highest mortality, followed by MI. The strongest predictors of mortality were a CMR diagnosis of cardiomyopathy and ST-elevation on presentation ECG.

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Prognostic Value of Cardiac Magnetic Resonance Tissue Characterization in Risk Stratifying Patients With Suspected Myocarditis

Abstract: CMR tissue characterization provides effective risk stratification in patients with suspected myocarditis.

Cited by 344 publications

References 34 publications

Myocarditis in Patients Treated With Immune Checkpoint Inhibitors

Myocarditis in Patients Treated With Immune Checkpoint Inhibitors

Immune Checkpoint Inhibitor-Associated Myocarditis

Prognostic Role of CMR and Conventional Risk Factors in Myocardial Infarction With Nonobstructed Coronary Arteries

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