Cardiology > Cardiotoxic Drugs

Background 

Cardiotoxic drugs are pharmacologic agents that adversely affect the heart’s structure or function, leading to arrhythmias, myocardial injury, contractile dysfunction, pericarditis, or even heart failure. These effects can be acute, chronic, dose-dependent, or idiosyncratic. Cardiotoxicity is a major concern in oncology, psychiatry, infectious diseases, and anesthesia, necessitating pre-treatment risk assessment and ongoing monitoring. 

Classification 

By Mechanism of Cardiotoxicity: 

• • Myocardial Injury 

• • • Anthracyclines (e.g., doxorubicin, daunorubicin): Dose-dependent, irreversible cardiomyopathy. 

• • • Trastuzumab: Reversible cardiomyopathy; HER2 inhibition in cardiac myocytes. 

• • Arrhythmogenesis 

• • • Antiarrhythmics: Amiodarone, sotalol, flecainide (QT prolongation, torsades de pointes). 

• • • Antipsychotics/Antidepressants: Haloperidol, citalopram (QT prolongation). 

• • • Antimicrobials: Macrolides, fluoroquinolones (QT prolongation). 

• • Coronary Vasospasm/Ischemia 

• • • 5-FU, capecitabine: Coronary vasospasm. 

• • • Cocaine, amphetamines: Catecholamine surge, ischemia, and arrhythmias. 

• • Pericardial Disease 

• • • Clozapine: Myocarditis and pericarditis. 

• • • Immune checkpoint inhibitors: Pericarditis, myocarditis. 

• • Hypertension and Thromboembolism 

• • • VEGF inhibitors (e.g., bevacizumab): Hypertension, arterial thrombotic events. 

Mechanism of Toxicity 

Cardiotoxicity results from direct myocyte injury, oxidative stress, mitochondrial dysfunction, impaired intracellular signaling, autonomic dysregulation, or inflammation. Anthracyclines cause free radical damage and apoptosis; trastuzumab disrupts HER2-mediated survival pathways in cardiac tissue. QT-prolonging drugs delay repolarization by inhibiting potassium channels (hERG blockade), predisposing to torsades de pointes. Cocaine increases sympathetic tone, leading to ischemia and arrhythmias. 

Prevalence 

• • Up to 10% of cancer patients on anthracyclines develop cardiomyopathy. 

• • 25% of patients treated with trastuzumab may show some decline in LVEF. 

• • Drug-induced QT prolongation contributes to 20–30% of torsades cases in hospitalized patients. 

• • Polypharmacy, especially in the elderly, increases cardiotoxic risk substantially. 

Indications for Use 

• • Chemotherapeutics: Cancer treatment (e.g., breast cancer, leukemia). 

• • Psychotropics: Schizophrenia, bipolar disorder, depression. 

• • Antibiotics/Antifungals: Severe infections. 

• • Antiarrhythmics: Atrial or ventricular arrhythmias. 

• • Immunotherapy: Solid tumors, hematologic malignancies. 

Symptoms of Toxicity 

• • Palpitations, syncope, dyspnea 

• • Fatigue, exercise intolerance 

• • Chest pain (coronary vasospasm) 

• • Orthopnea, peripheral edema (CHF) 

Signs/Drug-Specific Toxicity 

• • Anthracyclines: Reduced EF, overt CHF 

• • Trastuzumab: Asymptomatic EF drop, reversible dysfunction 

• • Amiodarone: Bradycardia, QT prolongation, pulmonary toxicity 

• • Haloperidol: QT prolongation, torsades de pointes 

• • 5-FU: Chest pain from coronary spasm 

• • Clozapine: Myocarditis, tachycardia, fever 

Essential Tests 

Baseline/Monitoring 

• • Echocardiography: Assess baseline and serial LVEF 

• • Electrocardiogram (ECG): QT interval, arrhythmia detection 

• • Troponin & BNP: Myocardial injury or stress 

• • Chest X-ray: Pulmonary congestion 

• • Serum electrolytes, renal & liver function: Especially with antiarrhythmics 

Drug-Specific Surveillance 

• • Doxorubicin: Baseline EF, repeat at cumulative doses >300 mg/m² 

• • Trastuzumab: Echo every 3 months 

• • QT-prolonging drugs: Serial ECGs, K⁺/Mg²⁺ levels 

• • Clozapine: Troponin, CRP if myocarditis suspected 

• • Cardiac MRI: Detects myocarditis or early fibrosis in chemotherapy patients 

Treatment 

I) Acute Management 

• • QT prolongation/torsades: IV magnesium sulfate, stop offending agent 

• • CHF: Loop diuretics, beta-blockers, ACEi/ARNI if LVEF reduced 

• • Arrhythmias: ACLS protocol; consider lidocaine over amiodarone if already on QT-prolonging drugs 

• • 5-FU cardiotoxicity: Discontinue agent, nitrates or calcium channel blockers for vasospasm 

• • Myocarditis: Corticosteroids, immunosuppression for immune-related events 

II) Long-Term/Definitive Therapy 

• • Discontinue or switch cardiotoxic agent if feasible 

• • Heart failure management: Guideline-directed therapy (ARNI, beta-blockers, MRA, SGLT2i) 

• • Oncology treatment adjustments: Use liposomal formulations (e.g., liposomal doxorubicin) 

• • Cardiology-oncology (cardio-oncology) consultation 

Medications 

Patient Education 

• • Inform about cardiotoxic signs: fatigue, palpitations, edema 

• • Adhere to ECG/echo schedule during therapy 

• • Maintain electrolyte balance (esp. with QT-prolonging meds) 

• • Encourage heart-healthy lifestyle: diet, exercise, BP/lipid control 

• • Vaccinate against influenza, pneumococcus, and COVID-19 to reduce cardiac stress 

Consults 

• • Cardio-oncology team: For drug management and surveillance 

• • Electrophysiologist: For arrhythmia evaluation or device implantation 

• • Oncologist: Dose modification or drug substitution 

• • Pharmacist: Drug interaction management, polypharmacy review 

• • Multidisciplinary care significantly enhances patient safety and therapeutic success