Anthracycline‐Induced Cardiomyopathy in Adults

Abstract

Anthracyclines are one of the most commonly used antineoplastic agent classes, and a core part of the treatment in breast cancers, hematological malignancies, and sarcomas. Their benefit is decreased by their well-recognized cardiotoxicity. The purpose of this review is to outline the presentation, mechanisms, diagnosis, and treatment of anthracyclines-induced cardiotoxicity. Symptomatic heart failure occurs in 2% to 5% of patients treated with anthrayclines and may be higher in older patients or patients with cardiovascular risk factors. The mechanisms involved in anthracycline-induced cardiotoxicity involve myocyte loss by apoptosis in the presence of a limited regenerative capacity. Once symptomatic, anthracycline-induced cardiotoxicity is associated with markedly decreased survival. Left ventricular ejection fraction (LVEF), mostly determined using echocardiography, is used to monitor patients treated with anthracyclines. As more than 1/3 of patients treated with anthracyclines do not recover their baseline LVEF once it is decreased, more sensitive echocardiographic indices of LV function such as myocardial deformation or biomarkers have been studied in patients monitoring. Cardioprotective treatments such as angiotensin-converting enzyme inhibitors, beta-blockers, iron chelators, statins, and metformin are also the topic of research efforts.

The heart after idarubicin overdose. Cardiac death in a patient with acute promyelocitic leukaemia

“…Herein, a significant colliquative myocytolysis, evident at the post mortem examination, underlies the sharp deterioration of cardiac function; The concept of necrotic damage as a central element of anthracycline-induced cardiotoxicity is not underscored in the literature [4], though it has crucial clinical implications: in fact, it provides a strong conceptual support to the serial assay of cardiac biomarkers (either troponins or B-type natriuretic peptides) for a prompt detection of cardiac damage in these patients [10].…”

“…occurs N1 year after treatment. It is associated with evolution towards overt chronic heart failure (CHF) with reduced systolic function, and/ or life-threatening arrhythmias [3,4]. Both early cardiotoxicity and late cardiotoxicity are dose-related.…”

“…infusion rate, concomitant or previous cancer therapies, advanced age, cardiac disease, and female sex. However, the strongest risk factor is the cumulative dose [3,4]. At each given cumulative dose, the risk of cardiotoxicity is likely to increase when the number of doses is reduced and the entity of the single dose increases.…”

“…No significant macroscopic abnormalities were detectable (Fig. 1, panel d), possibly owing to the rapid deterioration of cardiac function.Anthracyclines are extensively used in the treatment of haematological malignancies, breast cancers and sarcomas, yet their benefit is decreased by their cardiotoxicity; [3,4] this last seems to be related with the generation of free radical species, the disruption of sarcomeric structure, and the deterioration of DNA [3,4].Anthracycline cardiotoxicity can be categorized into three distinct types according to temporal criteria. Acute cardiotoxicity occurs during anthracycline infusion or within a week of therapy, and is usually transient and not dose-related.…”

“…Anthracyclines are extensively used in the treatment of haematological malignancies, breast cancers and sarcomas, yet their benefit is decreased by their cardiotoxicity; [3,4] this last seems to be related with the generation of free radical species, the disruption of sarcomeric structure, and the deterioration of DNA [3,4].…”