1. Definitions of the outcomes of cardiac toxicity.
| Trial | Outomes of cardiac toxicity as named in the trials | Explanation of the outcomes of cardiac toxicity |
| B31 | CHF | NYHA class III or IV CHF |
| Possible/probable cardiac death | Not reported | |
| BCIRG006 | Cardiac‐related death | Not reported |
| CHF | Grade 3/4, not further specified | |
| Cardiac ischaemia/infarction | Grade 3/4, not further specified | |
| Arrythmias | Grade 3/4, not further specified | |
| LVEF decrease | > 10% relative LVEF decline | |
| Buzdar | CHF | Not reported |
| LVEF decrease | Decrease of LVEF > 10% from the baseline | |
| FinHer | Cardiac infarction | Not reported |
| CHF | Not reported | |
| LVEF decrease | Any change in LVEF values between pre‐ and post‐treatment or decrease in LVEF > 20% less than pre‐treatment value or decrease in LVEF >10% resulting in a LVEF < 50% | |
| HERA | Death from cardiac causes | Death due to CHF, myocardial infarction, documented primary arrhythmia or sudden unexpected death after a definite or probable cardiac event without a documented alternative cause within 24 hours of a cardiac event |
| Symptomatic CHF | CHF considered symptomatic by a cardiologist and a decrease in LVEF of at least 10% from baseline to an LVEF of less than 50% at any time; it includes severe CHF | |
| Severe CHF | NYHA class III or IV CHF and a decrease in LVEF of at least 10% from baseline to an LVEF of less than 50% at any time | |
| Significant LVEF drop | Decrease in LVEF of 10% or more from baseline to a level below 50% | |
| Confirmed significant LVEF drop | Asymptomatic (NYHA class I) or mildly symptomatic (NYHA class II) significant drop in LVEF also confirmed on repeat LVEF assessment about 3 weeks after the first documented drop, or identified by the cardiac advisory board review | |
| NOAH | Cardiac events | Not defined |
| LVEF decrease | Asymptomatic (grade II decrease) | |
| N9831 | LVEF decrease | Any change in LVEF from registration level |
| CHF | NYHA class III or IV | |
| Possible/probable cardiac death | Sudden death without any documented cause | |
| Definite cardiac death | Death due to CHF, myocardial infarction or primary arrhyhtmia | |
| PACS‐04 | Severe LVEF decline | Decrease in LVEF to a level below 45% or decrease in LVEF to a level between 45% and 50% with a relative decrease of LVEF of 15% or more |
| Moderate LVEF decline between 45% and 49% | Decrease in LVEF to a level between 45% and 49% | |
| Mild LVEF decline between 50% and 55% | Decrease in LVEF to a level between 50% and 55% | |
| Heart failure | Not reported | |
| Cardiac death | Not reported |
CHF: congestive heart failure LVEF: left ventricular ejection fraction IV: intravenous NYHA: New York Heart Association