How to Monitor Cardiac Complications of Immune Checkpoint Inhibitor Therapy

Abstract

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.

Clinical implications of isolated troponinemia following immune checkpoint inhibitor therapy

“…Acute coronary syndromes are usually characterized by a rise and fall pattern in troponin levels while a steady increase is usually observed in myocarditis. 2,12,23 Second, elevated levels have previously been reported in patients with cancer which were subsequently associated with worse clinical outcomes, a more advanced tumor stage, and all-cause mortality. Furthermore, the deterioration of the patient's clinical status and/or progressive oncological disease during ICI treatment may cause troponin abnormalities.…”

“…cTn measurements are most often conducted at baseline and regular intervals up to 12 weeks (first three to four doses) after treatment initiation, covering the relatively short timeframe during which ICIinduced myocarditis is most likely to occur. 12 Cardiac biomarkers have become a cornerstone in the diagnosis of cardiovascular diseases. However, their role in cardio-oncology, more specifically in the active surveillance of ICI-mediated cardiotoxic effects and to identify patients at increased risk, is not clear.…”

“…cTn measurements are most often conducted at baseline and regular intervals up to 12 weeks (first three to four doses) after treatment initiation, covering the relatively short timeframe during which ICI-induced myocarditis is most likely to occur. 12 …”

“…Some guidelines have even recommended to withhold ICI therapy when abnormal biomarkers are detected in asymptomatic patients, although studies supporting this strategy are lacking. 1 , 12 Therefore the value and clinical implication of baseline troponin levels remain unclear, although it might be useful as a reference value to interpret subsequent changes during ICI therapy.…”

“…Acute coronary syndromes are usually characterized by a rise and fall pattern in troponin levels while a steady increase is usually observed in myocarditis. 2 , 12 , 23 …”