Identification and Management of Immune Checkpoint Inhibitor–Related Myocarditis: Use Troponin Wisely

Spallarossa, Paolo; Tini, Giacomo; Sarocchi, Matteo; Arboscello, Eleonora; Grossi, Francesco; Queirolo, Paola; Zoppoli, Gabriele; Ameri, Pietro

doi:10.1200/jco.18.02464

Cited by 38 publications

(37 citation statements)

References 21 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Though only few cases of severe myocarditis were reported in clinical trials of ICIs, subsequent observations suggest a significantly higher incidence (Spallarossa et al, 2018;Moslehi et al, 2018;Spallarossa et al, 2019), from 0.04% up to 1.14% (Palaskas et al, 2020), depicting ICI-related myocarditis as a severe form of cardiotoxicity with a fulminant clinical course often resulting in cardiogenic shock, advanced conduction disturbances, and ventricular arrhythmias. However, as most of the available evidence derives from case reports, case series, or retrospective studies (Johnson et al, 2016;Berg et al, 2017;Martinez-Calle et al, 2018;Moslehi et al, 2018;Samara et al, 2018;Yamaguchi et al, 2018), it may be flawed by reporting bias (i.e., only the most severe cases were described), whereas asymptomatic or mildly symptomatic forms may have gone unidentified or unreported.…”

Section: Why Monitoring Patients Treated With Immune Checkpoint Inhibmentioning

confidence: 99%

“…Thus, as the incidence of ICI-related myocarditis with a subtle presentation is still unknown, as well as its course if left untreated (Sarocchi et al, 2018), it cannot be excluded that in some cases subclinical myocarditis due to ICIs may even be self-limiting (Spallarossa et al, 2019). Hence, CV monitoring of patients receiving ICI therapy should not merely sought to diagnose overt cases of myocarditis; rather, its aim should be to recognize subclinical or asymptomatic cases, in order to avoid their progression.…”

Section: Why Monitoring Patients Treated With Immune Checkpoint Inhibmentioning

confidence: 99%

“…Whether is appropriate to screen for ICI-related myocarditis remains unknown. To be effective, such a strategy should result in early detection of myocarditis (and other cardiac irAEs), prompting an appropriate management plan to prevent a potentially severe course (Spallarossa et al, 2019). Nevertheless, screening should also be practically feasible and-most importantly-should not result in inappropriate withholding of a life-saving therapy.…”

Section: : Baseline Cardiology Evaluationmentioning

confidence: 99%

See 2 more Smart Citations

How to Monitor Cardiac Complications of Immune Checkpoint Inhibitor Therapy

et al. 2020

Self Cite

View full text Add to dashboard Cite

Immune-checkpoint inhibitors (ICIs) represent a successful paradigm in the treatment of cancer. ICIs elicit an immune response directed against cancer cells, by targeting the socalled immune checkpoints, key regulators of the immune system that when stimulated can dampen the immune response to an immunologic stimulus. Such response, however, is not entirely tumor-specific and may result in immune-related adverse events (irAEs), involving a number of organs and systems. Cardiovascular (CV) irAEs are rare, although potentially severe. In particular, several cases of ICI-related myocarditis with lifethreatening course have been reported: the possibility of fulminant cases, thus, requires a high level of awareness among both oncologists and cardiologists. Aggressive work-up and management of symptomatic patients taking ICIs is fundamental for early recognition and initiation of specific immunosuppressive therapies. Notably, myocarditis occurs within few weeks from ICIs initiation, offering opportunity for a targeted screening. Troponin testing is the cornerstone of this screening, yet uncertainties remain regarding timing and candidates. Moreover, troponins positivity should be carefully interpreted. We herein review the main aspects of ICI-related myocarditis and suggest a practical approach. In particular, we focus on the opportunities that a baseline CV evaluation offers for subsequent management by collecting clinical and instrumental data, essential for the interpretation of troponin results, for differential diagnosis and for the formulation of a diagnostic and therapeutic workup.

show abstract

Section: Why Monitoring Patients Treated With Immune Checkpoint Inhibmentioning

confidence: 99%

Section: Why Monitoring Patients Treated With Immune Checkpoint Inhibmentioning

confidence: 99%

Section: : Baseline Cardiology Evaluationmentioning

confidence: 99%

See 1 more Smart Citation

How to Monitor Cardiac Complications of Immune Checkpoint Inhibitor Therapy

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Thus, clinicians should be vigilant for signs of cardiac abnormalities at all times, and early diagnosis is important for improving the prognosis (Fig ). Once clinical symptoms such as chest tightness, palpitations, and dyspnea are present, a noninvasive work‐up should be started as soon as possible, including blood tests of inflammation (erythrocyte sedimentation rate and C‐reactive protein), myocardial enzymes, BNP and an electrocardiogram . Of note, this diagnostic testing must be observed dynamically, which would be helpful in ruling out false positive results and evaluating the severity of the disease.…”

Section: Diagnosis Of Ici‐associated Cardiotoxicitymentioning

confidence: 99%

“…If patients have a history of arrhythmias, Holter monitoring is suggested. The baseline tests including cTnI, NT‐proBNP/BNP, ECG, echocardiography, and inflammatory indicators are also needed . During ICI treatment at each visit, patients should be asked about cardiac‐related symptoms and receive careful physical examination.…”

Section: Early Detection Of Ici‐associated Cardiotoxicitymentioning

confidence: 99%

Clinical manifestation and management of immune checkpoint inhibitor‐associated cardiotoxicity

et al. 2019

View full text Add to dashboard Cite

Immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1), its ligand (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) have revolutionized cancer treatment by recovering the attack of T lymphocytes on the malignant cells. They have improved clinical outcomes dramatically in multiple types of advanced-stage malignancies. Even though the tolerance and safety profiles are generally good, it has been widely reported that ICIs can cause severe or fatal immune-related adverse events (irAEs), since the activated T lymphocytes are not specific for tumor cells. Cardiac irAEs appear to occur less frequently than irAEs in other organ systems but are notorious for high mortality. Here, we aim to identify and characterize the ICI-associated cardiotoxicity and summarize the optional diagnosis and treatment strategies.

show abstract

Cardiac magnetic resonance‐based layer‐specific strain in immune checkpoint inhibitor‐associated myocarditis

Li,

Zhao,

Wang

et al. 2024

ESC Heart Failure

View full text Add to dashboard Cite

AimsTo assess the different imaging characteristics between corticosteroid‐sensitive (CS) and corticosteroid‐refractory (CR) immune checkpoint inhibitor‐associated myocarditis (ICIaM) with cardiac magnetic resonance (CMR) and the potential CMR parameters in the early detection of CR ICIaM.Methods and resultsThirty‐five patients diagnosed with ICIaM and 30 age and gender‐matched cancer patients without a history of ICI treatment were enrolled. CMR with contrast was performed within 2 days of clinical suspicion. Left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE) were assessed by CMR. LV sub‐endocardial (GLSendo) and sub‐epicardial (GLSepi) global longitudinal strains were quantified by offline feature tracking analysis. CS and CR ICIaM were defined based on the trend of Troponin I and clinical course during corticosteroid treatment. All 35 patients presented with non‐fulminant symptoms upon initial assessment. Twenty patients (57.14%) were sensitive, and 15 (42.86%) were refractory to corticosteroids. Compared with controls, 22 patients (62.86%) with ICIaM developed LGE. LVEF decreased in CR ICIaM compared with the CS group and controls. GLSendo (−14.61 ± 2.67 vs. −18.50 ± 2.53, P < 0.001) and GLSepi (−14.75 ± 2.53 vs. −16.68 ± 2.05, P < 0.001) significantly increased in patients with CR ICIaM compared with the CS ICIaM. In patients with CS ICIaM, although GLSepi (−16.68 ± 2.05 vs. −19.31 ± 1.80, P < 0.001) was impaired compared with the controls, GLSendo was preserved. There was no difference in CMR parameters between LGE‐positive and negative groups. LVEF, GLSendo, and GLSepi were predictors of CR ICIaM. When LVEF, GLSendo, and GLSepi were included in multivariate analysis, only GLSendo remained an independent predictor of CR ICIaM (OR: 2.170, 95% CI: 1.189–3.962, P = 0.012). A GLSendo of ≥−17.10% (sensitivity, 86.7%; specificity, 80.0%; AUC, 0.860; P < 0.001) could predict CR ICIaM in the ICIaM cohort. Kaplan–Meier analysis showed that in patients with impaired GLSendo of ≥−17.10%, cardiovascular adverse events (CAEs) occurred much earlier than in patients with preserved GLSendo of <−17.10% (Log‐rank test P = 0.017).ConclusionsCR and CS ICIaM demonstrated different functional and morphological characteristics in different myocardial layers. An impaired GLSendo could be a helpful parameter in early identifying corticosteroid‐refractory individuals in the ICIaM population.

show abstract

Identification and Management of Immune Checkpoint Inhibitor–Related Myocarditis: Use Troponin Wisely

Abstract: Author affiliations and support information (if applicable) appear at the end of this article.

Cited by 38 publications

References 21 publications

How to Monitor Cardiac Complications of Immune Checkpoint Inhibitor Therapy

How to Monitor Cardiac Complications of Immune Checkpoint Inhibitor Therapy

Clinical manifestation and management of immune checkpoint inhibitor‐associated cardiotoxicity

Cardiac magnetic resonance‐based layer‐specific strain in immune checkpoint inhibitor‐associated myocarditis

Contact Info

Product

Resources

About