ABSTRACT

BACKGROUND - In patients at risk of cancer therapy-related cardiac dysfunction (CTRCD), initiation of cardio-protective therapy (CPT) is constrained by the low sensitivity of EF for minor changes in LV function. Global longitudinal strain (GLS) is a robust and sensitive marker of LV dysfunction, but existing observational data have been insufficient to support a routine GLS-guided strategy for CPT.

OBJECTIVE - To identify whether GLS-guided CPT prevents reduction in LVEF in patients undergoing potentially cardiotoxic chemotherapy, compared with usual care.

METHODS - In this international multicenter prospective randomized controlled trial, 331 anthracycline-treated patients with another heart failure risk factor were randomly allocated to CPT initiation guided by either ≥12% relative reduction in GLS (n=166) or >10% absolute reduction of LVEF (n=165). Patients were followed for EF and development of CTRCD (symptomatic EF reduction >5% or >10% asymptomatic to <55%) over 1 year.

RESULTS - Of 331 randomized patients, 2 died and 22 withdrew consent or were lost to follow-up. Among 307 patients (age 54±12 years, 94% women, baseline LVEF 59±6%, GLS -20.6±2.4%) with a median (IQR) follow-up of 1.02 (0.98-1.07) years, most (n=278) had breast cancer. HF risk factors were prevalent: 29% had hypertension and 13% had diabetes mellitus. At 1-year follow-up, although the primary outcome of change in LVEF was not significantly different between the two arms, there was significantly greater use of CPT, and fewer patients met CTRCD criteria in the GLS-guided than the EF-guided arm (5.8% vs 13.7%, p=0.02), and 1-year EF was 57±6% versus 55±7% (p=0.05). Patients diagnosed with CTRCD in the EF-guided arm had a larger reduction in LVEF at follow-up than in the GLS-guided arm (9.1±10.9% versus 2.9±7.4%, p=0.03).

CONCLUSIONS - Although the change in LVEF was not different between the two arms, GLS-guided CPT significantly reduced a meaningful fall of LVEF to the abnormal range. The results support the use of GLS in surveillance for CTRCD.