Myocarditis in the Setting of Cancer Therapeutics

Abstract

Recent developments in cancer therapeutics have improved outcomes but have also been associated with cardiovascular complications. Therapies harnessing the immune system have been associated with an immune mediated myocardial injury described as myocarditis. Immune checkpoint inhibitors (ICI) are one such therapy with an increasing number of case and cohort reports describing a clinical syndrome of ICI-associated myocarditis. While the full spectrum of ICI-associated cardiovascular disease still needs to be fully defined, described cases of myocarditis range from more "smoldering" to fatal ones. These observations in the clinic setting stand in contrast to outcomes from randomized clinical trials where myocarditis is a rare event that is investigator reported and lacking in a specific case definition. The complexities associated with diagnosis, as well as the heterogeneous clinical presentation of ICI-associated myocarditis, have made ascertainment and identification of myocarditis with high specificity challenging in clinical trials and other data sets, limiting the ability to better understand the incidence, outcomes and predictors of these rare events. Therefore, establishing a uniform definition of myocarditis for application in clinical trials of cancer immunotherapies will enable greater understanding of these events. We propose an operational definition of cancer therapy associated myocarditis characterizing a broad spectrum of disease to facilitate improved case ascertainment and in turn incidence, outcomes and risk factors. Bonaca et al.

The Role of Biomarkers in Cardio-Oncology

“…Cancer treatment has greatly advanced with the widespread use of immune checkpoint inhibitors [78]. Nevertheless, their increasing use is not without problems, specifically immune checkpoint inhibitor (ICI)-mediated myocarditis [79][80][81][82]. ICI-mediated myocarditis can be detected through an increase in serum troponin, which is one of the main diagnostic criteria for diagnosis in general cardiology.…”

How to Monitor Cardiac Complications of Immune Checkpoint Inhibitor Therapy

“…As discussed in the following paragraphs, presenting symptoms, signs, and laboratory data of ICI-related myocarditis can be mild and/or unspecific, and might be attributed to a broad spectrum of CV diseases, including acute and chronic coronary syndromes, left ventricular dysfunction, and arrhythmias. Collecting baseline clinical, ECG and echocardiography data would allow to recognize any change occurring during ICI therapy, facilitating early diagnosis of ICI-related myocarditis versus other cardiac disorders (Bonaca et al, 2019;Spallarossa et al, 2019).…”

“…In the case of minimal troponin abnormalities, ECG and echocardiography may be normal (Caforio et al, 2013), and should be repeated after few days if clinical suspicion and troponins elevation persist. If troponins remains high, with no other identifiable causes, cardiac magnetic resonance may be useful (Caforio et al, 2013;Bonaca et al, 2019). Clearly, these considerations are not valid if the patient is hemodynamically unstable: this scenario requires immediate admission to an intensive cardiac care unit and an aggressive diagnostic and therapeutic work-up.…”

Challenges and solutions in management of cardiotoxicity induced by checkpoint inhibitors

“…Väčšina publikovaných vedeckých a odborných článkov týkajúcich sa toxicity ICI donedávna neuvádzala kardiálnu toxicitu. So zvyšujúcim sa počtom pacientov, ktorí sú liečení ICI, sa postupne objavuje stále širšie spektrum ich KV nežiaducich účinkov, a to: myokarditída [10,[13][14][15][16][17][18][19][20][21], perikarditída [29,31], arytmie (predsieňové, komorové, kompletná atrioventrikulárna blokáda) [10,12,27], akútny infarkt myokardu [15], funkčné poškodenie ľavej komory [12,15,28], dilatačná kardiomyopatia [15], Tako-tsubo syndróm [30], vaskulitída [31], kardiogénny šok [8], náhla smrť [13]. Autori Escudier et al [12] publikovali v roku 2017 výsledky observačnej štúdie, ktorá analyzovala klinickú manifestáciu 30 prípadov pacientov, ktorých onkológovia odoslali pre podozrenie na kardiotoxicitu po liečbe ICI na ďalšie klinické odborné vyšetrenie.…”