Table 1

Chemotherapeutic classes and associations with short-term and long-term cardiotoxicities, diagnostic modalities and management/prevention

Chemotherapy cardiotoxicity	Major culprit chemotherapeutic classes (incidence)	Diagnostic methodologies	Management/prevention
Cardiomyopathy (with systolic and/or diastolic dysfunction)	Anthracyclines* Monoclonal antibodies* VSP inhibitors* Alkylating agents Antimicrotubule agents Antimetabolites Proteasome inhibitors*	Echocardiography Myocardial strain imaging by echo Cardiac MRI MUGA/RNA Biomarkers: troponin, BNP, newer biomarkers‡ Possible role for genetics	ACE-I/ARB Beta blockers Deferoxamine¶ Possible role for statins Possible role for ranolazine Serial LVEF/biomarker monitoring Discontinue chemotherapy, then reinstitute with LVEF recovery Long-term consideration for ICD and possible heart transplantation
Ischaemia	Antimetabolites (vasospasm) VSP—inhibitor TKIs (Mab and Smol)—arterial thrombosis Antimicrotubule agents (arterial thrombosis) Alkylating agents* Angiogenesis inhibitor—arterial thrombosis	ECG Troponin Stress test§ Coronary angiography Cardiac MRI	Nitrates for coronary spasms Aspirin for thrombosis risk Limited data for other antianginal agents
Thrombosis	Alkylating agents—venous Angiogenesis inhibitor—arterial VSP inhibitors— venous and arterial Histone deacetylase inhibitors—venous Immunomodulators—arterial Hormonal therapy (tamoxifen)—arterial/venous†	Doppler ultrasound CT angiography Other concern as for ischaemia above	Unfractionated heparin Low molecular weight heparin Fondapariux
Hypertension	VSP inhibitors/targeted therapies* VEGF trap Alkylating agents*	On-site blood pressure checks Ambulatory blood pressure monitoring	Amlodipine ACE-I/ARB Other antihypertensive regimens as third-line agents
Hypotension	Interferons Interleukins Monoclonal antibodies All-trans retinoic acid (differentiation syndrome)	On-site blood pressure checks Ambulatory blood pressure monitoring	Intravenous fluids Midodrine (if normal LVEF) Discontinue chemotherapy if in shock, then reinstitute when stable
Dysrhythmias	Interleukins Interferons Angiogenesis inhibitors (bradycardia) Antimicrotubule agents (bradycardia) Histone deacetylase inhibitors Non-VSP inhibitor small molecule TKIs Arsenic trioxide	ECG Telemetry	Beta blockers Propafenone Anticoagulation with low molecular weight heparin
QTc prolongation	Arsenic trioxide Histone deacetylase inhibitors Small molecule TKIs	ECG	Replete electrolytes (K/Mg) Serial ECG monitoring Discontinue other QTc prolonging drugs, where possible Discontinue chemotherapy agent, if significant risk of torsades
Pericardial disease	Busulfan* Non-VSP inhibitor small molecule TKIs	Echocardiography Cardiac MRI Cardiac CT	Pericardiocentesis Pericardial window Pericardial stripping (with constriction) Colchicine (if no interaction with chemotherapy) NSAIDs (if normal blood pressure and LVEF)

*Associated with long-term cardiotoxicity; does not necessarily apply to all agents within each mentioned drug class.
†Long-term toxicity as a function of protracted use.
‡Newer biomarkers with possible future promise include: serum galectin-3, ST-2, glycogen phosphorylase BB (GPBB), heart-type fatty acid-binding protein (H-FABP) and high-sensitivity C reactive protein (hs-CRP).81–84
§Stress test by Single-photon emission computed tomography (SPECT)-myocardial perfusion imaging, Fludeoxyglucose- (FDG)-Positron Emission Tomography (PET) scan and stress echocardiography. Of questionable utility, particularly if ischaemia is related to coronary vasospasm.
¶Deferoxamine particularly cardioprotective against anthracyclines.
Concern for chemotherapy–drug interactions with drugs that affect the cytochrome P-450 system (diltiazem, digoxin, amiodarone), as well as other QTc prolonging antiarrhythmics (flecainide, ibutilide, dofetilide, sotalol).85
Amlodipine is a very effective first-line agent for TKI-induced hypertension and proteinuria; ACE-I/ARBs are also useful (in addition to amlodipine) for proteinuria associated with these agents.
sARB, angiotensin receptor blocker; BNP, brain natriuretic peptide; ICD, implantable cardioverter defibrillator; LVEF, left ventricular ejection fraction; MUGA, multigated acquisition scan; NSAIDs, non-steroidal anti-inflammatory drugs, RNA, radionuclide angiography, TKI, tyrosine kinase inhibitor; VSP, vascular endothelial growth factor (VEGF) signalling pathway.