Table 1

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

Chemotherapy cardiotoxicityMajor culprit chemotherapeutic classes (incidence)Diagnostic methodologiesManagement/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.