The following are key points to remember from a state-of-the-art review on anthracycline cardiotoxicity in adult cancer patients:

1. Anthracyclines remain a cornerstone treatment for many solid and hematologic malignancies despite their cardiotoxic effects. They are essential for treating lymphomas, acute leukemias, and soft tissue sarcomas.
2. Cancer therapy-related cardiac dysfunction (CTRCD) is defined by decreases in left ventricular ejection fraction (LVEF) >10% to <50% and/or global longitudinal strain (GLS) >15% relative decrease from baseline. Right ventricular dysfunction may also occur with anthracycline therapy, though less studied than left ventricular effects.
3. Anthracycline-induced cardiotoxicity can manifest acutely (<1% of cases), early-onset (within first year, 98% of cases), or late-onset (>1 year after treatment). The risk of cardiotoxicity is dose-dependent, with higher cumulative doses associated with greater risk. The threshold between low and high heart failure risk is defined at 250-300 mg/m² for doxorubicin.
4. Mechanisms of anthracycline cardiotoxicity include oxidative stress, alterations in cell death pathways (apoptosis, pyroptosis, ferroptosis), and epigenetic changes. Genetic factors may influence individual susceptibility to anthracycline cardiotoxicity. Nearly 80 genes with single nucleotide polymorphisms have been linked to anthracycline-induced cardiotoxicity.
5. Key patient-related risk factors include age (>65 years), pre-existing cardiovascular disease, and hypertension, which can increase the likelihood of cardiotoxicity by up to 1.5-2 times compared to lower-risk groups. High-risk patients undergoing anthracycline treatment should receive imaging and biomarker evaluations every 3-6 months during treatment and annually for ≥5 years post-treatment.
6. Echocardiography is the first-line imaging modality for evaluating anthracycline-treated patients. GLS <16% or a relative modification >15% from baseline are considered risk markers.
7. The efficacy of primary prevention strategies with neurohormonal antagonists remains controversial, especially in low-risk patients. Recent trials (CECCY, PRADA, CardiacCARE) showed no significant cardioprotective effects in low- to moderate-risk patients.
8. Dexrazoxane is the only FDA-approved drug for preventing anthracycline-related cardiotoxicity. It is recommended for patients who have received a cumulative doxorubicin dose of 300 mg/m². Liposomal doxorubicin formulations may reduce cardiac accumulation and subsequent toxicity, allowing for higher cumulative doses.
9. Early detection and prompt initiation of heart failure therapy can lead to LVEF recovery in up to 82% of cases when started within 2 months post-chemotherapy. Management of anthracycline-induced CTRCD should follow current heart failure treatment guidelines.
10. Long-term cardiovascular surveillance is recommended for cancer survivors treated with anthracyclines, with follow-up tailored based on initial risk assessment. Dedicated survivorship clinics may improve long-term cardiovascular outcomes for cancer survivors, though resource constraints must be considered.

Clinical Topics: Cardio-Oncology, Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Anthracyclines, Cardio-oncology, Cardiotoxicity, Heart Failure

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