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. 2021 Dec 14;43(4):280–299. doi: 10.1093/eurheartj/ehab674

Table 5.

Definition of QTc prologation and Arrhythmias with Cancer Therapies

CTCAE Version 5*  
Event Definition Grades
QTc prolongation A finding of a cardiac dysrhythmia characterized by an abnormally long corrected QT interval.

  • Grade 1: Average QTc 450-480ms

  • Grade 2: Average QTc 481-500ms

  • Grade 3: Average QTc ≥501 ms; >60 ms change from baseline

  • Grade 4: Torsade de pointes; polymophic ventricular tachycardia; signs/symptoms of serious arrhythmia
Arrhythmias
Ventricular arrhythmia A disorder characterized by a dysrhythmia that originates in the ventricles.

  • Grade 1: Asymptomatic, intervention not indicated

  • Grade 2: Non-urgent medical intervention indicated

  • Grade 3: Urgent medical intervention indicated

  • Grade 4: Life-threatening consequences; hemodynamic compromise
Ventricular fibrillation A disorder characterized by a dysrhythmia without discernible QRS complexes due to rapid repetitive excitation of myocardial fibers without coordinated contraction of the ventricles Grade 4: Life-threatening consequences; hemodynamic compromise
Ventricular tachycardia A disorder characterized by a dysrhythmia with a heart rate greater than 100 beats per minute that originates distal to the bundle of His.

  • Grade 2: Non-urgent medical intervention indicated

  • Grade 3: Symptomatic, urgent intervention indicated

  • Grade 4: Life-threatening consequences; hemodynamic compromise
Atrial fibrillation A disorder characterized by a dysrhythmia without discernible P waves and an irregular ventricular response due to multiple reentry circuits. The rhythm disturbance originates above the ventricles.

  • Grade 1: Asymptomatic, intervention not indicated

  • Grade 2: Non-urgent medical intervention indicated

  • Grade 3: Symptomatic, urgent intervention indicated; device (e.g., pacemaker); ablation; new onset

  • Grade 4: Life-threatening consequences; embolus requiring urgent intervention
Atrial flutter A disorder characterized by a dysrhythmia with organized rhythmic atrial contractions with a rate of 200-300 beats per minute. The rhythm disturbance originates in the atria.

  • Grade 1: Asymptomatic, intervention not indicated

  • Grade 2: Non-urgent medical intervertion indicated

  • Grade 3: Symptomatic, urgent intervention indicated; device (e.g., pacemaker); ablation

  • Grade 4: Life-threatening consequences; embolus requiring urgent intervention
(Paroxysmal) atrial tachycardia A disorder characterized by a dysrhythmia with abrupt onset and sudden termination of atrial contractions with a rate of 150-250 beats per minute. The rhythm disturbance originates in the atria.

  • Grade 1: Asymptomatic, intervention not indicated

  • Grade 2: Non-urgent medical intervention indicated

  • Grade 3: Symptomatic, urgent intervention indicated; ablation

  • Grade 4: Life-threatening consequences; incompletely controlled medically; cardioversion indicated
Supraventricular tachycardia A disorder characterized by a dysrhythmia with a heart rate greater than 100 beats per minute that originates above the ventricles.

  • Grade 1: Asymptomatic, intervention not indicated

  • Grade 2: Non-urgent medical intervention indicated

  • Grade 3: Symptomatic, urgent intervention indicated

  • Grade 4: Life-threatening consequences
Sinus tachycardia A disorder characterized by a dysrhythmia with a heart rate greater than 100 beats per minute that originates in the sinus node.

  • Grade 1: Asymptomatic, intervention not indicated

  • Grade 2: Symptomatic, non-urgent medicali intervention indicated

  • Grade 3: Urgent medical intervention indicated
Atrioventricular block, first degree A disorder characterized by a dysrhythmia with a delay in the time required for the conduction of an electrical impulse through the atrioventricular (AV) node beyond 0.2 seconds; prolongation of the PR interval greater than 200 milliseconds.

  • Grade 1: Asymptomatic, intervention not indicated

  • Grade 2: Non-urgent medical intervention indicated
Atrioventricular block, second degree, Mobitz (type) II A disorder characterized by a dysrhythmia with relatively constant PR interval prior to the block of an atrial impulse. This is the result of intermittent failure of atrial electrical impulse conduction through the atrioventricular (AV) node to the ventricles.

  • Grade 1: Asymptomatic, intervention not indicated

  • Grade 2: Symptomatic; medical intervention indicated

  • Grade 3: Symptomatic and incompletely controlled medically, or controlled with device (e.g., pacemaker); new onset

  • Grade 4: Life-threatening consequences; urgent intervention indicated
Atrioventricular block, second degree, Mobitz type I A disorder characterized by a dysrhythmia with a progressively lengthening PR interval prior to the blocking of an atrial impulse. This is the result of intermittent failure of atrial electrical impulse conduction through the atrioventricular (AV) node to the ventricles.

  • Grade 1: Asymptomatic, intervention not indicated

  • Grade 2: Symptomatic; medical intervention indicated

  • Grade 3: Symptomatic and incompletely controlled medically, or controlled with device (e.g., pacemaker)

  • Grade 4: Life-threatening consequences; urgent intervention indicated
Atrioventricular block, complete (third degree) A disorder characterized by a dysrhythmia with complete failure of atrial electrical impulse conduction through the AV node to the ventricles.

  • Grade 2: Non-urgent medical intervention indicated

  • Grade 3: Symptomatic and incompletely controlled medically, or controlled with device (e.g., pacemaker); new onset

  • Grade 4: Life-threatening consequences; urgent intervention indicated
Conduction disorder A disorder characterized by pathological irregularities in the cardiac conduction system.

  • Grade 1: Mild symptoms, intervention not indicated

  • Grade 2: Non-urgent medical intervention indicated

  • Grade 3: Symptomatic, urgent intervention indicated

  • Grade 4: Life-threatening consequences
Sick sinus syndrome A disorder characterized by a dysrhythmia with alternating periods of bradycardia and atrial tachycardia accompanied by syncope, fatigue and dizziness.

  • Grade 1: Asymptomatic, intervention not indicated

  • Grade 2: Symptomatic, intervention not indicated; change in medication initiated

  • Grade 3: Symptomatic, intervention indicated

  • Grade 4: Life-threatening consequences; urgent intervention indicated
Sinus bardycardia A disorder characterized by a dysrhythmia with a heart rate less than 60 beats per minute that originates in the sinus node.

  • Grade 1: Asymptomatic, intervention not indicated

  • Grade 2: Symptomatic, intervention not indicated; change in medication initiated

  • Grade 3: Symptomatic, intervention indicated

  • Grade 4: Life-threatening consequences; urgent intervention indicated
IC-OS 2021 consensus
QTc prolongation QTcF < 480ms Acceptable: continue current treatment
QTcF 480-500ms Prolonging: proceed with caution; minimize other QT prolonging medications, replete electrolytes
QTcF >500ms Prolonged: stop treatment and evaluate. May require dose reduction or alternative therapy
Arrhythmias
Ventricular arrhythmia

  • 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death116

  • 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death117
Ventricular tachycardia (VT), including polymorphic VT (torsades de pointes)

  • 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death116

  • 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death117
Ventricular fibrillation

  • 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death116

  • 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death117
Atrial fibrillation

  • 2020 ESC Guidelines for Management of Atrial Fibrillation118

  • 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation119
Atrial flutter

  • 2020 ESC Guidelines for Management of Atrial Fibrillation118

  • 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation119
Atrial tachycardia

  • 2019 ESC Guidelines on Supraventricular Tachycardia120

  • 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society121
Supraventricular tachycardia

  • 2019 ESC Guidelines on Supraventricular Tachycardia120

  • 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society121
Sinus tachycardia

  • 2019 ESC Guidelines on Supraventricular Tachycardia120

  • 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society121
Sinus bradycardia 2018 ACC/AHA/HRS Guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay122
Sick sinus syndrome 2018 ACC/AHA/HRS Guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay122
Atrioventricular block first, second and third degree 2018 ACC/AHA/HRS Guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay122
Conduction disorder (disease) 2018 ACC/AHA/HRS Guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay122
*

Grade 5 = death.