Cardiotoxicity of Anthracyclines

Abstract

Cardiotoxicity is a feared side effect that may limit the clinical use of anthracyclines. It may indeed affect the quality of life and survival of patients with cancer, regardless of oncological prognosis. This paper provides an overview of anthracycline-induced cardiotoxicity in terms of definition, classification, incidence, risk factors, possible mechanisms, diagnosis, and treatment. We also report effective strategies for preventing cardiotoxicity. In addition, we discuss limiting current approaches, the need for a new classification, and early cardiotoxicity detection and treatment. Probably, anthracycline-induced cardiotoxicity is a continuous phenomenon that starts from myocardial cell injury; it is followed by left ventricular ejection fraction (LVEF) and, if not diagnosed and cured early, progressively leads to symptomatic heart failure. Anthracycline-induced cardiotoxicity can be detected at a preclinical phase. The role of biomarkers, in particular troponins, in identifying subclinical cardiotoxicity and its therapy with angiotensin-converting enzyme inhibitors (mainly enalapril) to prevent LVEF reduction is a recognized and effective strategy. If cardiac dysfunction has already occurred, partial or complete LVEF recovery may still be obtained in case of early detection of cardiotoxicity and prompt heart failure treatment.

Keywords: ACE-inhibitors; anthracyclines; beta-blockers; cardiotoxicity; early detection; prevention; reversibility; troponin.

Figure 1

Graphical representation of several doxorubicin-targeted cell types, with potential side effects and cellular and molecular events evoked by the drug. From Cappetta et al. (11).

Figure 2

Possible strategies for cancer drug-induced cardiotoxicity detection, prevention, and treatment. AC, anthracyclines; ACEI, angiotensin-converting enzyme inhibitors; BB, beta-blockers; CV, cardiovascular; GLS, global longitudinal strain; HF, heart failure; LVD, left ventricular dysfunction; RAS, renin-angiotensin system. From Cardinale et al. (8).

Figure 3

LVEF in patients with cardiotoxicity and with partial (triangle) or full (square) recovery with heart failure therapy. Data are mean ± SD. CT, chemotherapy; HF, heart failure. From Cardinale et al. (15).

Figure 4

(A) Percentage of patients who recovered (Responders), according to the time elapsed from anthracycline administration and the start of heart failure therapy. (B) Relationship between maximal LVEF during the follow-up period and log time elapsed from chemotherapy and the start of treatment [time-to-heart failure (HF) treatment]. From Cardinale et al. (31).

Figure 5

(A) Percentage of patients developing cardiac dysfunction in the enalapril-treated group (ACEI Group) and controls. (B) Incidence of cardiac events in patients treated with ACEI Group and in Controls. Modified from Cardinale et al. (90).