Anthracycline cardiotoxicity: an update on mechanisms, monitoring and prevention

Abstract

Anthracycline chemotherapy causes dose-related cardiomyocyte injury and death leading to left ventricular dysfunction. Clinical heart failure may ensue in up to 5% of high-risk patients. Improved cancer survival together with better awareness of the late effects of cardiotoxicity has led to growing recognition of the need for surveillance of anthracycline-treated cancer survivors with early intervention to treat or prevent heart failure. The main mechanism of anthracycline cardiotoxicity is now thought to be through inhibition of topoisomerase 2β resulting in activation of cell death pathways and inhibition of mitochondrial biogenesis. In addition to cumulative anthracycline dose, age and pre-existing cardiac disease are risk markers for cardiotoxicity. Genetic susceptibility factors will help identify susceptible patients in the future. Cardiac imaging with echocardiographic measurement of global longitudinal strain and cardiac troponin detect early myocardial injury prior to the development of left ventricular dysfunction. There is no consensus on how best to monitor anthracycline cardiotoxicity although guidelines advocate quantification of left ventricular ejection fraction before and after chemotherapy with additional scanning being justified in high-risk patients. Patients developing significant left ventricular dysfunction with or without clinical heart failure should be treated according to established guidelines. Liposomal encapsulation reduces anthracycline cardiotoxicity. Dexrazoxane administration with anthracycline interferes with binding to topoisomerase 2β and reduces both cardiotoxicity and subsequent heart failure in high-risk patients. Angiotensin inhibition and β-blockade are also protective and appear to prevent the development of left ventricular dysfunction when given prior or during chemotherapy in patients exhibiting early signs of cardiotoxicity.

Successful treatment of primary donor‐derived human herpesvirus‐8 infection and hepatic Kaposi Sarcoma in an adult liver transplant recipient

“…Liposomal anthracyclines (doxorubicin or daunorubicin) are generally recommended as first‐line systemic chemotherapy for KS. Liposomal formulations are generally well tolerated and associated with a lower risk of cardiac dysfunction compared to non‐liposomal formulations . Antiviral agents such as cidofovir, ganciclovir, and foscarnet have demonstrated activity against HHV‐8 in vitro but have not been shown to be effective in treating established KS .…”

Do current approaches to assessing therapy related adverse events align with the needs of long-term cancer patients and survivors?

“…Modulatory factors such as variable treatment adherence rates, drug-drug interactions, access to care, and patient comorbidities result in a range of patient experiences and healthcare system demands [23]. Even for a specific treatment-related AE (e.g., treatment of aromatase inhibitor-induced chronic pain or approaches to monitoring ejection fraction changes associated with anthracycline cardiotoxicity), the nature of the supportive approaches that are adopted may vary considerably from site to site [24,25].…”

A circular RNA regulator quaking: a novel gold mine to be unfolded in doxorubicin-mediated cardiotoxicity

“…Anthracycline administration is associated with dose-related cardiomyocyte injury and death, leading to heart failure. The main mechanism of anthracycline cardiotoxicity is thought to be by inhibition of topoisomerase 2β, resulting in activation of cell death pathways and inhibition of mitochondrial biogenesis (2). …”