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Table 3 Cancer therapy-related cardiovascular toxicity definitions

CTRCD Symptomatic CTRCD (HF)a,b Very severe HF requiring inotropic support, mechanical circulatory support, or consideration of transplantation

Severe HF hospitalization Moderate Need for outpatient intensification of diuretic and HF therapy Mild Mild HF symptoms, no intensification of therapy required

Asymptomatic CTRCD Severe New LVEF reduction to ,40%

Moderate New LVEF reduction by ≥10 percentage points to an LVEF

of 40–49% OR New LVEF reduction by ,10 percentage points to an LVEF of 40– 49% AND either new relative decline in GLS by .15% from baseline OR new rise in cardiac biomarkersc

Mild LVEF ≥50% AND new relative decline in GLS by .15% from baseline

AND/OR new rise in cardiac biomarkersc

ICI myocarditis (either pathohistological diagnosis or clinical diagnosis) Pathohistological diagnosis (EMB) Multifocal inflammatory cell infiltrates with overt cardiomyocyte loss by light microscopy Clinical diagnosisd cTn elevation (new or significant change from baseline)e with 1 major criterion or 2 minor criteria, after exclusion of ACS and acute infectious myocarditis based on clinical suspicionf

Major criterion: • CMR diagnostic for acute myocarditis (modified Lake Louise criteria)g Minor criteria: • Clinical syndrome (including any one of the following: fatigue, myalgias, chest pain, diplopia, ptosis,

shortness of breath, orthopnoea, lower-extremity oedema, palpitations, light-headedness/dizziness, syncope, muscle weakness, cardiogenic shock) • Ventricular arrhythmia (including cardiac arrest) and/or new conduction system disease • Decline in LV systolic function, with or without regional wall motion abnormalities in a non-Takotsubo pattern • Other immune-related adverse events, particularly myositis, myopathy, myasthenia gravis • Suggestive CMRh

Severity of myocarditis • Fulminant: Haemodynamic instability, HF requiring non-invasive or invasive ventilation, complete or

high-grade heart block, and/or significant ventricular arrhythmia • Non-fulminant: including symptomatic but haemodynamically and electrically stable patients and incidental cases diagnosed at the same time as other immuno-related adverse events. Patients may have

reduced LVEF but no features of severe disease • Steroid refractory: non-resolving or worsening myocarditis (clinical worsening or persistent troponin elevation after exclusion of other aetiologies) despite high-dose methylprednisolone

Recovery from myocarditis • Complete recovery: Patients with complete resolution of acute symptoms, normalization of biomarkers, and recovery of LVEF after discontinuation of immunosuppression. CMR may still show LGE

or elevated T1 due to fibrosis, but any suggestion of acute oedema should be absent • Recovering: Ongoing improvement in patient clinical symptoms, signs, biomarkers, and imaging parameters, but not yet normalized, while on tapering doses of immunosuppression

Vascular toxicity (for general cardiology definitions, see Supplementary data, Table S1) Asymptomatic vascular toxicity CAD Symptomatic vascular toxicity Stroke

PAD Transient ischaemic attack Carotid artery disease MI Venous thrombosis ACS Arterial thrombosis CCS Peripheral vasoreactivity PAD

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