Cardiotoxicity encompasses a broad spectrum of adverse cardiovascular effects caused by medications, ranging from asymptomatic electrocardiographic changes to life-threatening arrhythmias, heart failure, and myocardial infarction. As cancer therapies have become more effective and patient survival has improved, cardiotoxicity has emerged as a major concern in oncology, where the cardiovascular side effects of chemotherapy and targeted agents can limit treatment and impair long-term quality of life. Recognition of drug-induced cardiac injury requires a high index of suspicion, as the presentation may be indistinguishable from primary cardiac disease.
Mechanisms of injury vary substantially depending on the drug class. Direct myocyte injury is mediated by oxidative stress, mitochondrial dysfunction, and apoptosis, as exemplified by anthracyclines. Electrophysiologic effects result from blockade of cardiac ion channels, particularly the hERG potassium channel, leading to prolongation of the QT interval and increased risk of torsades de pointes. Vascular effects include coronary vasospasm, endothelial dysfunction, and accelerated atherosclerosis. Hemodynamic effects arise from drug-induced hypertension, fluid retention, or negative inotropy. Some agents produce cardiotoxicity through multiple mechanisms simultaneously.
Anthracyclines, particularly doxorubicin, produce a well-characterized form of cardiotoxicity that can present acutely, early, or late after treatment. The acute form occurs within hours of infusion with transient arrhythmias and left ventricular dysfunction. The early-onset chronic form develops during treatment or within one year and manifests as a dilated cardiomyopathy. The late-onset form may appear decades after treatment completion, particularly in childhood cancer survivors. The risk is dose-dependent, with cumulative doses exceeding 450 to 550 mg per square meter associated with a sharply increased incidence of heart failure. Dexrazoxane, an iron-chelating agent, provides cardioprotection by reducing free radical formation.
Trastuzumab, a monoclonal antibody used in HER2-positive breast cancer, causes a reversible form of cardiac dysfunction that differs from anthracycline-induced injury by not producing ultrastructural myocyte damage. The risk is substantially higher in patients who have received prior or concurrent anthracycline therapy. Regular echocardiographic monitoring of left ventricular ejection fraction is standard during treatment. 5-Fluorouracil (5-FU) and its prodrug capecitabine cause coronary vasospasm, presenting as chest pain, myocardial ischemia, and, rarely, myocardial infarction, typically during continuous infusion. The mechanism involves endothelial dysfunction and vasoconstriction rather than atherosclerotic plaque rupture.
Tyrosine kinase inhibitors such as sunitinib and sorafenib produce cardiotoxicity through inhibition of off-target kinases involved in cardiomyocyte survival and function. Sunitinib is associated with hypertension, left ventricular dysfunction, and heart failure in up to 15 percent of treated patients. QT prolongation is a concern with many drugs, including macrolide antibiotics, fluoroquinolones, antipsychotics, and antiemetics. The risk of torsades de pointes is increased by hypokalemia, hypomagnesemia, bradycardia, concurrent use of multiple QT-prolonging drugs, and genetic polymorphisms in cardiac ion channels.
Clinical presentation ranges from asymptomatic reductions in ejection fraction to overt heart failure with dyspnea, edema, and fatigue. Arrhythmias may cause palpitations, syncope, or sudden cardiac death. Myocardial ischemia presents with chest pain, electrocardiographic changes, and elevated cardiac biomarkers. The diagnosis is established through a combination of clinical assessment, electrocardiography, echocardiography, and cardiac biomarker measurement, particularly troponin and natriuretic peptides.
Diagnosis and monitoring require baseline cardiac assessment before initiating potentially cardiotoxic therapy and serial surveillance during and after treatment. Echocardiography with global longitudinal strain assessment can detect subclinical myocardial dysfunction before ejection fraction declines. Cardiac magnetic resonance imaging provides detailed assessment of myocardial structure, function, and tissue characterization.
Prevention and management include identification of preexisting cardiovascular risk factors, selection of less cardiotoxic regimens when possible, limiting cumulative doses, and using cardioprotective agents such as dexrazoxane. When cardiotoxicity develops, standard heart failure therapy with beta-blockers, angiotensin-converting enzyme inhibitors, and diuretics is initiated. Collaboration between oncologists and cardiologists in cardio-oncology programs optimizes outcomes by balancing cancer treatment efficacy against cardiovascular risk.
