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Domain

Cardio-Oncology & Cardio-Obstetrics

Modules

Cancer Therapy-Related Cardiac Dysfunction

Baseline risk, surveillance, and intervention thresholds.

Mechanisms of Cardiotoxicity

Type I — AnthracyclinesTopoisomerase-2β DNA damage,mitochondrial oxidative stressDose-dependent, cumulative,often irreversibleType II — HER2-targetedBlocks neuregulin-1/ErbB2survival signalingNot dose-dependent,often reversible

Anthracyclines cause Type I cardiotoxicity through topoisomerase-2β-mediated DNA damage and mitochondrial oxidative stress in cardiomyocytes, producing dose-dependent, cumulative, and often irreversible myocyte injury. HER2-targeted agents such as trastuzumab cause Type II cardiotoxicity by blocking neuregulin-1/ErbB2 survival signaling that cardiomyocytes rely on for stress adaptation, resulting in reversible dysfunction that is generally not dose-dependent. These distinct mechanisms explain why anthracycline injury tends to be permanent and cumulative-dose-related, while trastuzumab-related dysfunction often recovers with drug interruption and guideline-directed therapy, and why combining both agents markedly increases cardiotoxic risk.

High-Risk Regimens

Anthracyclines (dose-dependent). HER2-targeted (trastuzumab). TKIs (sunitinib, sorafenib, ponatinib). ICIs (myocarditis — rare but often fulminant). Radiation to mediastinum.

Baseline Assessment

HFA-ICOS baseline risk (low/moderate/high/very high) guides monitoring frequency. Baseline TTE with LVEF and GLS in high-risk. Repeat per regimen and risk.

CTRCD Definition (2022 ESC)

Mild (asymptomatic)ModerateSevere / symptomaticGLS ↓≥15% or troponin riseLVEF drop to 40–49%LVEF <40%, or HF symptomsAsymptomatic mild: GLS decline ≥15% relative OR troponin elevation. Moderate: LVEF drop ≥10 to 40–49%. Severe: LVEF <40%. Symptomatic mirrors + HF symptoms.

Management

Cardioprotection with ACEi/ARB and beta-blocker in CTRCD — most can continue cancer therapy with cardioprotection. Discontinue in severe/symptomatic. ICI myocarditis: high-dose steroids, hold ICI.

Surveillance Strategy During Cardiotoxic Therapy

Baseline echocardiography with strain before starting anthracyclines or HER2-targeted therapy, followed by surveillance imaging during treatment, allows detection of cardiotoxicity before overt heart failure develops. A significant drop in global longitudinal strain, even with preserved ejection fraction, should prompt cardiology involvement and consideration of cardioprotective therapy.
Clinical pearls
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GLS falls before LVEF — early detection allows preemptive intervention (SUCCOUR-CTRCD).
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Cardiotoxicity is often reversible with early recognition and treatment — do not wait for symptoms.
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Anthracycline cardiotoxicity risk rises sharply above a cumulative dose of roughly 250 mg/m2 doxorubicin-equivalent, reinforcing the dose-dependent nature of Type I injury.
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Trastuzumab-related (Type II) cardiotoxicity is typically not dose-dependent and often reversible with therapy interruption, unlike classic anthracycline injury.
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The 2022 ESC definition of CTRCD requires either a ≥15% relative decline in GLS or an LVEF drop below the lower limit of normal, formalizing strain-based criteria alongside LVEF.
Related guidelines