Assessment and Management of Cardiotoxicity in Hematologic Malignancies

Abstract

With the increasing overall survival of cancer patients due to recent discoveries in oncology, the incidence of side effects is also rising, and along with secondary malignancies, cardiotoxicity is one of the most concerning side effects, affecting the quality of life of cancer survivors. There are two types of cardiotoxicity associated with chemotherapy; the first one is acute, life-threatening but, fortunately, in most of the cases, reversible; and the second one is with late onset and mostly irreversible. The most studied drugs associated with cardiotoxicity are anthracyclines, but many new agents have demonstrated unexpected cardiotoxic effect, including those currently used in multiple myeloma treatment (proteasome inhibitors and immunomodulatory agents), tyrosine kinase inhibitors used in the treatment of chronic myeloid leukemia and some forms of acute leukemia, and immune checkpoint inhibitors recently introduced in treatment of refractory lymphoma patients. To prevent irreversible myocardial damage, early recognition of cardiac toxicity is mandatory. Traditional methods like echocardiography and magnetic resonance imaging are capable of detecting structural and functional changings, but unable to detect early myocardial damage; therefore, more sensible biomarkers like troponins and natriuretic peptides have to be introduced into the current practice. Baseline assessment of patients allows the identification of those with high risk for cardiotoxicity, while monitoring during and after treatment is important for early detection of cardiotoxicity and prompt intervention.

The Value of Troponin as a Biomarker of Chemotherapy-Induced Cardiotoxicity

“…Direct or endogenous (e.g., AC)—also called primary cardiomyopathy—which is a consequence of the direct toxic effects of chemotherapy on the myocardium and is caused by myocardial cell loss, necrosis, and apoptosis mediated by oxidative stress [ 10 ].…”

“…Late or chronic cardiomyopathy related to cumulative doses of AC, with an onset after more than 1 year and which is expressed as an arrythmia or LV dysfunction [ 10 ].…”

“…Different mechanisms are involved in the decline of cardiac function due to cancer therapies. The cardiomyocyte damage can be: Direct or endogenous (e.g., AC)—also called primary cardiomyopathy—which is a consequence of the direct toxic effects of chemotherapy on the myocardium and is caused by myocardial cell loss, necrosis, and apoptosis mediated by oxidative stress [ 10 ]. Indirect (e.g., trastuzumab, VEGF inhibitors), which is caused by factors that do not have a direct toxic effect on cardiomyocytes, but that contribute to a decline in cardiac function.…”

“… Early-onset chronic cardiotoxicity, which is more common (20–30% with asymptomatic decreases in the LVEF, or symptomatic HF in 1.6–2.1%) and can lead to irreversible cardiac dysfunction [ 35 ]. Late or chronic cardiomyopathy related to cumulative doses of AC, with an onset after more than 1 year and which is expressed as an arrythmia or LV dysfunction [ 10 ]. …”

Anticancer Drug-Induced Cardiotoxicity: Insights and Pharmacogenetics

“…Linschoten et al in their study observed two women who suffered from heart failure after months of receiving anticancer therapy. The genetic screening study witnessed mutations in TTN, encoding the myofilament titin responsible for the occurrence of heart failure [ 153 ].…”