Early Detection and Prediction of Cardiotoxicity in Chemotherapy-Treated Patients

Abstract

As breast cancer survival increases, cardiotoxicity associated with chemotherapeutic regimens such as anthracyclines and trastuzumab becomes a more significant issue. Assessment of the left ventricular (LV) ejection fraction fails to detect subtle alterations in LV function. The objective of this study was to evaluate whether more sensitive echocardiographic measurements and biomarkers could predict future cardiac dysfunction in chemotherapy-treated patients. Forty-three patients diagnosed with breast cancer who received anthracyclines and trastuzumab therapy underwent echocardiography and blood sampling at 3 time points (baseline and 3 and 6 months during the course of chemotherapy). The LV ejection fraction; peak systolic myocardial longitudinal, radial, and circumferential strain; echocardiographic markers of diastolic function; N-terminal pro–B-type natriuretic peptide; and high-sensitivity cardiac troponin I were measured. Nine patients (21%) developed cardiotoxicity (1 at 3 months and 8 at 6 months) as defined by the Cardiac Review and Evaluation Committee reviewing trastuzumab. A decrease in longitudinal strain from baseline to 3 months and detectable high-sensitivity cardiac troponin I at 3 months were independent predictors of the development of cardiotoxicity at 6 months. The LV ejection fraction, parameters of diastolic function, and N-terminal pro–B-type natriuretic peptide did not predict cardiotoxicity. In conclusion, cardiac troponin plasma concentrations and longitudinal strain predict the development of cardiotoxicity in patients treated with anthracyclines and trastuzumab. The 2 parameters may be useful to detect chemotherapy-treated patients who may benefit from alternative therapies, potentially decreasing the incidence of cardiotoxicity and its associated morbidity and mortality.

Global and regional patterns of longitudinal strain in screening for chemotherapy-induced cardiotoxicity

“…5 Although multicenter studies 20,21 and a recent meta-analysis 13 support the use of speckle tracking echocardiography in screening for cardiotoxicity in patients treated with anthracyclines and trastuzumab, it is still not used routinely in clinical practice. The results of our study are in line with those of previous studies, and highlight the value of longitudinal strain for both assessment of subclinical cardiotoxicity and identification of patients at high risk of developing CIC.…”

Cardiac Imaging: Multimodality Advances and Surveillance Strategies in Detection of Cardiotoxicity

“…In a multicenter study comparing echocardiographic parameters in patients with HF, global longitudinal strain (GLS) assessment, a parameter evaluating longitudinal aspect of myocardial contraction using deformation imaging, appeared to have a higher and more reliable prognostic value than LVEF for the prediction of cardiac events and cardiac deaths [20]. 2D speckle tracking strain has already been evaluated in studies for a total of more than 700 patients concomitantly to the administration of cardiotoxic anticancer agents, with encouraging results concerning its capability to diagnose subclinical LV dysfunction of subsequent clinical relevance [21][22][23][24][25][26][27]. Based on these data, serial strain measurements are suggested during anticancer treatment [11••].…”

“…High-sensitive troponins assays may have a greater interest for the detection of subclinical myocardial damage. Sawaya et al recently demonstrated that highsensitive Tn-I assays in combination with echocardiography strain imaging increase the accuracy of early detection and prediction of CTRCD in breast cancer patients treated with anthracyclines and trastuzumab [22,24]. The ASE/EACVI consensus document recommends serial Tn-I levels be drawn with a chemotherapy regimen potentially associated with type I or type II toxicities or in case of their sequential administration [11••].…”

“…In this study, CMR, performed at baseline and at 12 months, documented an increase in LV volumes, a decrease in LVEF, and a late gadolinium enhancement in the LV lateral wall in the CTRCD group. Sawaya et al studied a very similar population with similar biomarkers [22]. NT-proBNP was not associated with any predictive value but high-sensitive Tn-I at 3 months appeared as an independent predictor of cardiotoxicity at 6 months.…”

“…Trastuzumab was initiated with close monitoring of LVEF (every 3 weeks) using multimodality approach (2DE, 3DE, and GLS) and with cardioprotective treatment titrated to the maximal tolerated dosage. CMR cardiac magnetic resonance, CO cardiac output, CTRCD cancer therapeutic-related cardiac dysfunction, GLS global longitudinal strain, LVEDV left ventricular end diastolic volume, LVEF left ventricular ejection fraction, LVESV left ventricular end systolic volume, SV stroke volume anticancer agents [21][22][23][24][25][26][27]. Cutoffs value for relative percentage reduction during surveillance which are suggestive of clinically significant cardiotoxicity has been proposed in the ASE/EACVI expert consensus document [11••], although further studies are needed to validate these findings.…”