Diastolic dysfunction can precede systolic dysfunction on MUGA in cancer patients receiving trastuzumab-based therapy

Trastuzumab (T) and anthracycline (A)-based chemotherapy is considered the standard of care in human epidermal growth factor receptor-2+ overexpressing breast cancer, but requires monitoring for known cardiotoxicity using left ventricular (LV) ejection fraction (EF) every 3-4 months during treatment. It is not conclusively established whether diastolic dysfunction (DD) precedes LVEF decrease in patients developing trastuzumab-induced cardiotoxicity (TIC).

The aim was to elucidate whether DD precedes LVEF decrease in trastuzumab-treated patients being monitored with radionuclide multigated acquisition for TIC.

Patients treated with T±A-based chemotherapy who had undergone multigated acquisition were selected by date range (January 2006-September 2015). Up to four scans were analyzed per patient: (a) pre-A therapy, (b) pre-T therapy, (c) 4 months into T therapy, and (d) at end of T therapy. Baseline referred to the first scan of each patient (i.e. pre-A or pre-T). LV systolic and DD were defined as follows: EF less than 50% or a 10-point decrease from baseline and LV peak filling rate (PFR) less than 2.5 end-diastolic volume/s and time to peak LV filling rates (TPFR) greater than 180 ms, respectively.

A total of 202 patients were screened for this study, of whom 153 had received A therapy (5.1±4.1 months duration) before T, 192 had 4 months of follow-up data, and 146 had 4 months of follow-up data and beyond (10.5±5.0 months). LVEF decreased with A and T therapy (P<0.005), but remained stable between 4 months and the final exam (P=0.26). In patients with normal diastolic function at baseline (45.5%), PFR decreased with A and T, and DD preceded SD by 73 days on average. In the remaining patients, with abnormal diastolic function at baseline (54.5%), PFR did not change over the course of treatment (P>0.1), nor did TPFR (P>0.3).

Patients with normal diastolic function at baseline receiving trastuzumab±anthracycline adjuvant therapy may develop DD before SD, therefore offering an opportunity for early referral to cardiologists to optimize cardiovascular risk factors and manage cardiotoxicity.