Clinical outcomes of chemotherapy-induced subclinical left ventricular systolic dysfunction among breast cancer patients detected using echocardiographic global longitudinal strain

Abstract

Abstract Background Echocardiographic global longitudinal strain (GLS) detects early subclinical left ventricular (LV) systolic dysfunction, before the occurrence of a decreased LV ejection fraction. However, our local data is lacking to determine its impact to clinical outcomes. Purpose The study aimed to determine the clinical outcomes of breast cancer patients who developed subclinical LV systolic dysfunction as determined by an abnormal GLS post-chemotherapy. Methods This retrospective cohort study included 99 breast cancer patients who underwent anthracycline and/or HER-2 receptor inhibitor chemotherapy from January 1, 2016 to December 31, 2018 in a single tertiary hospital. Clinical outcomes of all-cause mortality and overt heart failure were compared between those with normal and abnormal GLS post-chemotherapy. Results The prevalence of subclinical LV systolic dysfunction was 18%, wherein 28% of them had subsequent overt heart failure, and 33% expired. Abnormal GLS occurred at a mean 3.5 months (range 1–8 months) after initiation of chemotherapy and at 8 months (range 6–10 months) after the entire chemotherapy sessions. Development into heart failure was observed at a mean of 6.7 months (range 4–12 months) after occurrence of abnormal GLS. Hypertension and age >56 years were determined to be risk factors. Beta-blockers, ACE inhibitors and statins seemed to be non-protective in our cohort. Abnormalities in GLS were observed at a mean dose of 260 mg/m2 of epirubicin, lower than the dose described as high risk in the literature (600 mg/m2 for epirubicin). In trastuzumab, abnormal GLS occurred as early as 1 month after initiation. LVEF had no significant change within 2 months (p=0.56), but was significantly lower within 12 months post-chemotherapy (p=0.005). All-cause mortality was 3-fold higher (RR=3.00; p=0.02), and the risk to develop heart failure was 4 times higher (RR=4.74; p=0.008) in those with abnormal GLS. Conclusion The development of abnormal GLS post-chemotherapy was associated with subsequent development of overt heart failure and increased all-cause mortality. Abnormal GLS occurred at lower doses of epirubicin and as early as 1 month after initiating trastuzumab. We recommend echo surveillance with GLS monitoring beginning >250 mg/m2 with anthracycline (and after 1–2 months of Trastuzumab), and to repeat at 1–2 months and 9–12 months post-chemotherapy. Funding Acknowledgement Type of funding source: None