Global longitudinal strain: an early marker for cardiotoxicity in patients treated for breast cancer

Abstract

Background Patients treated with anthracyclines and trastuzumab are at increased risk of developing heart failure. Early diagnosis and treatment may prevent irreversible left ventricular (LV) dysfunction. This study investigates whether subclinical deterioration of global longitudinal strain (GLS) is a more reliable early predictor for LV dysfunction than three-dimensional (3D) LV ejection fraction (LVEF). Methods Adult patients receiving anthracyclines and trastuzumab for breast cancer who had serial echocardiographic follow-up were included in this retrospective study. The primary endpoint was the necessity to temporarily pause chemo- or immunotherapy due to declining LVEF (decline in 3D LVEF of > 10 percentage points to < 53%). Linear mixed-effects models were used to assess the longitudinal evolution of 3D LVEF and GLS over time. Results Fifty-one women were included, mean age 54 (50.5–57.6) years, with a total of 216 follow-up echocardiograms (mean follow-up 1.1 ± 0.45 years). GLS and 3D LVEF were significantly correlated (Spearman’s rho: −0.36, p < 0.001). A decrease in GLS significantly predicted a lower LVEF on the subsequent echocardiogram [ß −0.6, 95% confidence interval (CI) (−1.0 to −0.2), p < 0.006]. Conversely, prior LVEF did not significantly predict GLS on the subsequent echocardiogram [ß −0.04, 95% CI −0.1 to −0.01, p = 0.12]. Nine patients reached the primary endpoint. On average, patients who reached the primary endpoint had a relative decrease of 15% GLS at day 205 and an absolute 10% decrease of LVEF to LVEF < 53% at day 235. Discussion GLS is able to identify subclinical LV dysfunction earlier than 3D LVEF measurement in women undergoing treatment for breast cancer with anthracyclines followed by trastuzumab.

Global longitudinal strain in cardio-oncology: worth our trouble or more trouble than it’s worth?

“…The current study by van der Linde et al does provide some additional support for the potential GLS holds in detecting cardiotoxicity [7]., However, at the time of writing, there is no evidence indicating that this should change our current healthcare, other than considering intensifying screening in these specific individuals [9]. One way this field will certainly lean is towards the implementation of artificial intelligence and deep learning to predict patients' risk of developing cardiotoxicity.…”

“…In this issue of the Netherlands Heart Journal, van der Linde et al describe the potential added value of global longitudinal strain (GLS) in detecting trastuzumab-induced cardiac dysfunction in patients with breast cancer and a preserved LV systolic function at baseline [7]. Over 200 echocardiograms performed in 51 patients were available, showing a significant decline in three-dimensional LVEF in 18% of the cohort.…”

New Insights in the Era of Clinical Biomarkers as Potential Predictors of Systemic Therapy-Induced Cardiotoxicity in Women with Breast Cancer: A Systematic Review

“…Additional studies have validated the role of HER2 codon 655 A>G in increasing the risk of trastuzumab-induced cardiotoxicity in French, Chinese, and Canadian patients [ 221 , 229 ]. In contrast, two studies have demonstrated no association between HER2 lle655Val and CTRCD suggesting that additional studies are required to clarify the role of this SNP in the prediction and detection of CTRCD in breast cancer patients [ 212 , 213 ]. Based on these conflicting results, studies have focused on risk factors that may influence trastuzumab-mediated cardiotoxicity in the presence of the HER2 lle655Val SNP including alcohol consumption, BMI, diabetes, hypertension, and combination treatment with anthracyclines [ 229 ].…”

HER2-Targeted Therapy—From Pathophysiology to Clinical Manifestation: A Narrative Review

“…Global longitudinal strain is a validated early marker of myocardial function impairment, also in the setting of trastuzumab-induced myocardial damage. The study conducted by Van der Linde et al (2023) demonstrates that LVGLS change occurs prior to the decline in LVEF by approximately one month [84]. The European Society of Cardiology recommends considering starting neurohormonal cardioprotection after substantial reduction in GLS during ongoing maintained trastuzumab therapy [49].…”