Atorvastatin and left ventricular global longitudinal strain during anthracycline-based chemotherapy

Abstract Background Anthracycline exposure may lead to a decline in the left ventricular ejection fraction (LVEF) and the development of heart failure. Left ventricular global longitudinal strain (LV GLS) is an early marker of anthracycline-associated cardiotoxicity, carries prognostic value for asymptomatic individuals, and is less influenced by loading conditions than LVEF. A ≥15% relative decrease in LV GLS is a guideline-defined predictor of future adverse cardiac events in oncology patients. In the STOP-CA clinical trial, atorvastatin preserved LVEF during anthracycline-based chemotherapy; however, its effect on the decrease in GLS is unknown. Purpose We investigated whether atorvastatin reduces the risk of a significant decline in LV GLS in newly diagnosed lymphoma patients undergoing anthracycline chemotherapy. Methods STOP-CA recruited 300 new lymphoma patients in nine centers across the US and Canada. Participants were randomized to atorvastatin (n=150) or placebo (n=150) for 12 months. Cardiac MRI was performed at baseline and 12 months after anthracycline initiation. Long-axis (two, three, and four chambers) cine sequences were contoured endo and epicardially to calculate GLS (Medis Suite v4.0/QStrain 4.4, Leiden, The Netherlands) with feature-tracking (FT). The primary outcome of interest was the proportion of participants in each group with a ≥15% relative decrease in the absolute value of GLS. Clinical events were evaluated at 24 months. Results Of the 300 participants, 188 (98 in the atorvastatin group, median age 52 years, 48% female) had paired data of LV GLS. The baseline GLS was similar between groups (22.5±2.9% with atorvastatin vs. 22.8±3.5% with placebo, P=0.65), with the 12-month follow-up values remaining similar (21.1±2.9% vs. 20.9±3.2%, P=0.78). The proportion of participants with a ≥15% relative decrease at 12 months was numerically lower with atorvastatin; however, it was not statistically significant (19% vs. 28%, P=0.23). Those with a ≥15% relative decrease in GLS had a mean -4.71±5.55% decrease in LVEF, as opposed to a mean -1.86±5.24% decline in those not meeting the endpoint (P0.001). Every 10-year increase in age at randomization was associated with a 1.34 times higher odds ratio (OR) of meeting the primary endpoint (95% confidence interval CI 1.07-1.72, P=0.014). A ≥15% relative decrease in GLS was not associated with worse clinical outcomes; however, a follow-up value of 18% was associated with an OR of 6.6 (15% vs. 3%, 95% CI 1.13-38.02, P=0.017) for subsequent heart failure (HF; event n=8) and an OR of 4.4 (19% vs. 5%, 95% CI 1.01-18.02, P=0.024) for cardiac hospitalization (event n=12) with both assessed at 24 months. Conclusion Atorvastatin did not significantly reduce the risk of a ≥15% relative decline in LV GLS in lymphoma patients undergoing anthracycline-based chemotherapy. An abnormal follow-up GLS value at 12 months was associated with worse HF and cardiac hospitalization outcomes at 24 months.Abstract summary figure Changes in LV GLS - Table