Table 1.

Cardiovascular Toxicity of Anticancer Therapy^{4a,5,7,9,10,34,43,44,60}

Agent	Toxicity	Proposed Mechanisms	Age-Related Toxicity
Anthracyclines	Left ventricular dysfunction CHF Pericarditis and/or myocarditis	Generation of reactive free radicals Induction of apoptosis Changes in ATP production Mitochondrial DNA damage Downregulation of mRNA expression for sarcoplasmic reticulum calcium ATPase	Increased risk at age > 65 years Risk increases as cumulative dose increases
Fluorouracil and/or capecitabine	Angina Myocardial infarction Arrhythmia CHF Cardiogenic shock Sudden death	Vasospasm Direct myocardial toxicity Coronary artery thrombosis Development of arteritis Induction of apoptosis	Unknown
Bortezomib	Left ventricular dysfunction CHF	Induction of endoplasmic reticulum stress after proteasome inhibition	Unknown
Cyclophosphamide	CHF	Direct endothelial injury Intracapillary microemboli Coronary vasospasm	Unknown
Docetaxel and/or paclitaxel	CHF Myocardial ischemia Bradycardia	Cremophor EL vehicle induction of histamine release Effects on Purkinje system and/or extracardiac autonomic control	Unknown
Cisplatin	Thrombosis	Platelet activation and aggregation Disruption of endothelial integrity Elevated von Willebrand factor leading to vasospasm	Unknown
Trastuzumab	Left ventricular dysfunction CHF	Inhibition of HER2 ATP depletion Disruption of mitochondrial integrity	Increased risk at age > 80 years
Bevacizumab	CHF Arterial thrombosis Angina Myocardial infarction Hypertension	Inhibition of VEGF Reduction in nitric oxide and prostacyclin Reduction of myocardial capillary density Cardiac fibrosis	Inconclusive
Lapatinib	Left ventricular dysfunction CHF QT prolongation	Inhibition of HER2 ATP depletion Disruption of mitochondrial integrity	Unknown
Imatinib	CHF	Inhibition of c-Abl	Unknown
Dasatinib	CHF QT prolongation	Inhibition of c-Abl Inhibition of Src	Unknown
Nilotinib	QT prolongation	Unknown	Unknown
Sunitinib	CHF Hypertension	Mitochondrial damage Inhibition of tyrosine kinase that regulates hypertensive stress in myocardiocytes Induction of apoptosis ATP depletion Inhibition of VEGF	Unknown
Sorafenib	Myocardial ischemia Hypertension	Inhibition of VEGF Induction of apoptosis	Unknown
Erlotinib	Myocardial ischemia Myocardial infarction Thrombosis	Unknown	Unknown
Thalidomide and/or lenalidomide	Thrombosis Bradycardia	Interaction of platelets and endothelium Increased platelet aggregation and von Willebrand factor Activation of vasovagal pathway	Unknown
Arsenic trioxide	QT prolongation	Prolongation of action potential	Unknown
Histone deacetylase inhibitors	Thromboembolism QT prolongation	Unknown	Unknown
Radiotherapy	Coronary artery disease Acute pericarditis Myocarditis CHF Valvular disease Conduction disease	Generation of reactive oxygen species Endothelial damage Development of arteritis Development of cardiac fibrosis	Unknown

Abbreviations: ATP, adenosine triphosphate; CHF, congestive heart failure; HER2, human epidermal growth factor receptor 2; mRNA, messenger RNA; VEGF, vascular endothelial growth factor.