Cancer treatment-related cardiotoxicity
Cancer treatment-related cardiotoxicity covers five distinct syndromes: irreversible, cumulative-dose-dependent anthracycline cardiomyopathy; typically reversible trastuzumab/HER2-targeted left ventricular dysfunction; radiation-induced coronary, pericardial, valvular, and conduction disease appearing years after chest irradiation; tyrosine kinase inhibitor and VEGF-inhibitor hypertension and QT prolongation; and immune checkpoint inhibitor myocarditis, a distinct fulminant entity requiring urgent high-dose corticosteroids and permanent drug discontinuation.
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What this article covers
- Overview
Cancer treatment-related cardiotoxicity spans at least five mechanistically distinct syndromes, not one disease: irreversible, cumulative-dose-dependent anthracycline cardiomyopathy; typically…
- Epidemiology
Chronic anthracycline cardiomyopathy has early onset (within 1 year) in 1.6%-2.1% and late onset (dose-related) in up to 5%; at a cumulative doxorubicin dose of 550 mg/m2, heart failure incidence…
- Risk factors
High cumulative anthracycline dose (doxorubicin =250 mg/m2, epirubicin =600 mg/m2) is the strongest predictor of chronic anthracycline cardiomyopathy; combined anthracycline-trastuzumab or anthracycline-radiation each raise risk further.
- Pathophysiology
Anthracyclines generate iron-catalyzed free radicals, intercalate into DNA, and inhibit topoisomerase II, directly killing cardiomyocytes, which have limited regenerative capacity, producing…
- Clinical features
Anthracycline cardiomyopathy presents with heart-failure symptoms (dyspnea, orthopnea, edema, fatigue) that may not appear until 10-20 years later; rare acute presentations include arrhythmia, heart…
- Differential diagnosis
Acute coronary syndrome - single-vessel wall-motion abnormality and ischemic ECG changes, confirmed on angiography.
- Diagnosis
Cancer therapy-related cardiac dysfunction (CTRCD) is defined echocardiographically by any of: reduced LVEF with heart-failure signs/symptoms, an asymptomatic LVEF decline of 10% or more to below…
- Management
First, for confirmed CTRCD, start guideline-directed heart failure therapy once the patient is euvolemic, continued indefinitely: lisinopril (ACE inhibitor) 2.5-5 mg PO once daily, titrated to a…
- Complications
Fulminant myocarditis with cardiogenic shock and arrhythmia or heart block is the most acutely life-threatening complication, specific to ICI therapy.
- Prognosis
ICI myocarditis carries the highest short-term mortality of the five syndromes when fulminant, with progression to shock or fatal arrhythmia possible within days; early recognition and immediate steroids materially change outcome.
- Prevention
Obtain baseline cardiovascular risk assessment and echocardiography before starting an anthracycline, trastuzumab, or other cardiotoxic agent, choosing an equally effective non-cardiotoxic alternative when one exists.
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