The spectrum of cardiovascular toxicity with immune checkpoint inhibitors (ICIs) is heterogeneous, from myocarditis to noninflammatory manifestations (e.g., heart failure, arrhythmias, and atherosclerosis-related events).

The mechanisms subtending ICI-related cardiovascular toxicity remain speculative, although translational approaches have described an auto-antigen-driven mechanism as a potential immunological basis of myocarditis.

The incidence of cardiovascular toxicity is estimated to reach 10%; myocarditis is rare albeit possibly hyper-acute (within first two cycles) and fatal (mortality 50%). ICI combination regimens represent the most important risk factor for myocarditis (twofold increased risk).

Myocarditis may frequently (40%) co-occur with myositis/myasthenia gravis (the so-called overlap syndrome), with a fulminant (after first ICI infusion) and fatal (75%) outcome. Neurological symptoms may precede the occurrence of myocarditis.

The 2022 European Society of Cardiology (ESC) guideline on cardio-oncology provided, for the first time, recommendations on cardiovascular assessment and monitoring before, during, and after anticancer treatments, mostly on the basis ofexpert opinion.

The actual transferability of ESC recommendations depends on local aspects, including the availability of a dedicated cardio-oncology service.

Increased awareness is needed across different medical specialties, including general practitioners and emergency practitioners, to timely inform a multidisciplinary workup.

The ESC guidelines recommended cardiac biomarkers (troponin and natriuretic peptides) and ECG at baseline and before each of the first three cycles of ICI administration. Transthoracic echocardiogram is also recommended at baseline in high-risk patients (e.g., those receiving ICI combination). Conversely, there is no consensus among oncological guidelines (e.g., ASCO, ESMO) on the need for baseline ECG and troponin testing. Of note, the risk of myocarditis cannot be predicted on the basis of baseline parameters.

Additional serial monitoring of creatin kinase, aldolase, and acetylcholine receptor antibodies could be considered in high-risk patients to early detect myocarditis and overlap syndrome.

Timely high-dose corticosteroids for 3 days represent the first-line approach, whereas targeted immunomodulating drugs are used in refractory cases. Rechallenge with ICIs deserves a careful case-by-case evaluation.