Anthracycline- and trastuzumab-induced cardiotoxicity: a retrospective study

Abstract

Some chemotherapeutic agents cause cardiotoxic effects including reduction in left ventricular ejection fraction (LVEF) and occasionally congestive heart failure. Anthracyclines and HER2 monoclonal antibodies are common offenders, but clinical practice data on LVEF changes, risk factors and acute recovery is lacking. We retrospectively examined the electronic medical record at an academic medical center for receipt of anthracyclines and/or trastuzumab from 2000 to 2013 in cancer patients. Patient characteristics and serial LVEF assessments were collected. Patients with and without LVEF decline were analyzed by univariate and multivariate analysis. A total of 549 patients were identified with anthracycline/trastuzumab use and 216 had multiple LVEF assessments. Only 27 of the 216 patients who had multiple LVEF assessments at multiple occasions suffered a clinically significant LVEF fall (12.5 %), and symptomatic CHF was rare (0.5 %). Compared to unaffected patients, those with a fall in LVEF were more likely to have hypertension, hyperlipidemia or coronary artery disease (CAD). Concomitant trastuzumab and anthracycline use was a risk factor (36 vs 9.5 % for anthracycline alone, p < 0.001). The median time from start of chemotherapy to reduced LVEF was 202 days (5–3008). On multivariate analysis, hypertension and use of trastuzumab remained independent predictors of LVEF fall. Acute recovery in LVEF was observed in 44 % of patients. LVEF changes from cancer therapies are frequent and hard to predict. Hypertension, hyperlipidemia and CAD are associated with LVEF decline. Acute recovery of LVEF is observed in those experiencing treatment-related cardiotoxicity. Attention to timely interruption of cardiotoxic chemo is recommended.

Biomarkers for the detection of apparent and subclinical cancer therapy-related cardiotoxicity

“…dysfunction following high cumulative dose anthracycline therapy (e.g., doxorubicin 700 mg/m²) (32). Combination therapy with chest/mediastinal radiation or HER-2 inhibitors (e.g., trastuzumab) as commonly used in breast and gastric cancer therapy can further multiply anthracycline-induced cardiotoxic effects (33)(34)(35)(36)(37)(38)(39). Cumulative dose, intravenous bolus administration, female sex, hypertension, diabetes mellitus and known cardiovascular disease are risk factors for the development of anthracycline cardiotoxicity (5,7,32,35,40).…”

“…Chemotherapy protocols containing alkylating agents or anthracyclines have shown plasma troponin I elevation in 12-33% in adults (43,54,(62)(63)(64)(65) and up to 47% in children (56). The cardiotoxic effect of the human epidermal growth factor receptor 2 inhibitor (HER2 inhibitor) trastuzumab with or without anthracycline-based chemotherapy has been extensively studied as it affects a significant portion of breast cancer patients (37,38,66). Trastuzumab monotherapy caused elevated troponin I in 14% while in combination therapy of trastuzumab with anthracyclines, elevated troponin I was observed in 21-24% of patients (54,63,67).…”

Klotho Improves Cardiac Function by Suppressing Reactive Oxygen Species (ROS) Mediated Apoptosis by Modulating Mapks/Nrf2 Signaling in Doxorubicin-Induced Cardiotoxicity

“…Heart failure has been found correlated with administration of chemotherapy, which is considered as cardiotoxicity [ 2 ]. It was been reported that reduction in left ventricular ejection fraction (LVEF) was impaired in 12.5% of cancer patients receiving anthracycline/trastuzumab administration [ 3 ]. Though several mechanisms have been proposed, such as endoplasmic reticulum stress, mitochondria damage, and calcium overload [ 4 – 6 ], the exact molecular mechanisms of cardiotoxicity are still unclear.…”

A novel scoring system to estimate chemotherapy-induced myocardial toxicity: Risk assessment prior to non-anthracycline chemotherapy regimens

“…Hamirani et al showed that the presence of arterial hypertension, hyperlipidaemia, and coronary artery disease correlates with reduced LV function in 549 patients after anthracycline or trastuzumab therapy [18] . In agreement with this study, we found that the CardTox-Score – which includes five cardiovascular risk factors – showed high predictive value for the development of CIMC in our small internal validation cohort.…”