AUTHOR=Posch Florian , Niedrist Tobias , Glantschnig Theresa , Firla Saskia , Moik Florian , Kolesnik Ewald , Wallner Markus , Verheyen Nicolas , Jost Philipp J. , Zirlik Andreas , Pichler Martin , Balic Marija , Rainer Peter P. 

TITLE=Left ventricular ejection fraction and cardiac biomarkers for dynamic prediction of cardiotoxicity in early breast cancer

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.933428

DOI=10.3389/fcvm.2022.933428

ISSN=2297-055X

ABSTRACT=Background/Purpose: To quantify the utility of monitoring LVEF, hs-cTnT, and NT-proBNP for dynamic cardiotoxicity risk assessment in women with HER2+ early breast cancer undergoing neoadjuvant/adjuvant trastuzumab-based therapy. Methods: We used joint models of longitudinal and time-to-event data to analyze 1,136 echocardiography reports and 326 hs-cTnT and NT-proBNP measurements from 185 women. Cardiotoxicity was defined as a 10% decline in LVEF below 50% and/or clinically overt heart failure. Results: Median pre-treatment LVEF was 64%, and 19 patients (10%) experienced cardiotoxicity (asymptomatic n=12, during treatment n=19). Pre-treatment LVEF strongly predicted for cardiotoxicity (Subdistribution Hazard Ratio per 5% increase in pre-treatment LVEF=0.68, 95%CI: 0.48-0.95, p=0.026). In contrast, pre-treatment hs-cTnT and NT-proBNP were not consistently associated with cardiotoxicity. During treatment, the longitudinal LVEF trajectory dynamically identified women at high risk of developing cardiotoxicity (Hazard ratio per 5% LVEF increase at any time of follow-up=0.36, 0.20-0.65, p=0.005). Thirty-four patients (18%) developed an LVEF decline ≥5% from pre-treatment to first follow-up (“early LVEF decline”). One-year cardiotoxicity risk was 6.8% in those without early LVEF decline and pre-treatment LVEF≥60% (n=117), 15.9% in those with early LVEF decline or pre-treatment LVEF<60% (n=65), and 66.7% in those with early LVEF decline and pre-treatment LVEF<60% (n=3), respectively (Gray’s test p<0.0001). Conclusion: Cardiotoxicity risk is low in the two thirds of women with HER2+ early breast cancer who have pre-treatment LVEF ≥60% and no early LVEF decline >5% during trastuzumab-based therapy. The longitudinal LVEF trajectory but not hs-cTnT or NT-proBNP allows for a dynamic assessment of cardiotoxicity risk in this setting.