Cardiotoxicity of anticancer treatments

Abstract

Patients with cancer can experience adverse cardiovascular events secondary to the malignant process itself or its treatment. Patients with cancer might also have underlying cardiovascular illness, the consequences of which are often exacerbated by the stress of the tumour growth or its treatment. With the advent of new treatments and subsequent prolonged survival time, late effects of cancer treatment can become clinically evident decades after completion of therapy. The heart's extensive energy reserve and its ability to compensate for reduced function add to the complexity of diagnosis and timely initiation of therapy. Additionally, modern oncological treatment regimens often incorporate multiple agents whose deleterious cardiac effects might be additive or synergistic. Treatment-related impairment of cardiac contractility can be either transient or irreversible. Furthermore, cancer treatment is associated with life-threatening arrhythmia, ischaemia, infarction, and damage to cardiac valves, the conduction system, or the pericardium. Awareness of these processes has gained prominence with the arrival of strategies to monitor and to prevent or to mitigate the effects of cardiovascular damage. A greater understanding of the mechanisms of injury can prolong the lives of those cured of their malignancy, but left with potentially devastating cardiac sequelae.

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

“…In 1 retrospective analysis, past anthracycline use was the only significant predictor of trastuzumab‐induced cardiotoxicity 54. Additionally, concomitant use of anthracycline or short period (3 weeks versus 3 months) between anthracycline use and administration of trastuzumab appear to increase the risk of cardiac adverse events in some studies 14, 55. Given these observations, many cancer centers are now favoring chemotherapeutic regimens that do not contain anthracyclines when HER2 targeted therapies are used 56…”

Integrating cardiomyocytes from human pluripotent stem cells in safety pharmacology: has the time come?

“…Physical damage is primarily associated with drugs specifically designed to be cytotoxic, such as chemotherapeutic agents in cancer treatment (Cross et al , 2015; Ewer and Ewer, 2015). These drugs induce mitochondrial damage (Varga et al , 2015), increase oxidative stress (Cross et al , 2015), activate DNA damage response pathways (Mercurio et al , 2016) and increase apoptosis (Arola et al , 2000).…”

“…The net outcome for the heart may be many fewer CMs, with a residual proportion being vital but unhealthy. As a result, the contractile force of cardiac muscle is reduced over time (Ewer and Ewer, 2015). In turn, this reduces the ejection fraction from the left ventricle, and heart failure ensues (Cardinale et al , 2015).…”

“…The resulting contractile and electrical dysfunction often leads to abnormal heartbeat and life‐threatening arrhythmias (Ewer and Ewer, 2015; Gintant et al , 2016). Arrhythmia is currently an immense burden on public health, with millions of people at risk of heart malfunction because of the cardiotoxic effects of drugs (Rubinstein and Camm, 2002; Vejpongsa and Yeh, 2014; Viskin et al , 2015).…”

Trastuzumab in Female Breast Cancer Patients With Reduced Left Ventricular Ejection Fraction

“…Adverse events typically associated with chemotherapy, such as alopecia, myelosuppression, and nausea and vomiting are not seen with trastuzumab. Cardiotoxicity, either leading to an asymptomatic decrease in left ventricular ejection fraction (LVEF) or heart failure (HF), remains the most important adverse effect 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16…”