Effect of statin on right ventricle function in breast cancer patients treated with anthracycline

Objectives Investigate the effect of rosuvastatin on cardiotoxicity in patients with breast cancer receiving standard anthracycline-based regimen by the dynamic of coupling between right ventricular (RV) contractile function and pulmonary artery systolic pressure (RV-PA coupling) assessed with TAPSE/PAPs index. Background Anthracycline-induced reactive oxygen species lead to oxidative stress, DNA damage and apoptosis, mediated by anthracycline-induced inhibition of topoisomerase II, that are the key mechanisms for anthracycline-induced cardiotoxicity. Accumulating evidence has suggested a role of the small Ras homolog (Rho) GTPase in DNA damage response. Statins are anti-inflammatory and anti-oxidative drugs and inhibitors of small Rho GTPases, which are a major factor in the development of oxidative stress. Studies have suggested that the RV may be more vulnerable to injury from anthracyclines, and early RV dysfunction may predict anthracycline-induced cardiotoxicity. It was shown that TAPSE/PAPs measured on echocardiography strongly correlated with the invasive assessment of RV-PA coupling and unmasked the early occurrence of symptoms and an initial depression in the RV functional reserve. Till now, there has been no research on the pharmacological effects of RV-PA coupling(1). Methods 226 consecutive patients with breast cancer, mean age 52 ±10, with low HFA/ICOS risk before therapy scheduled for standard anthracycline-based regimen therapy, were examined before and after the completion of anthracycline therapy (median cumulative dose of 250 mg/m2). Clinical assessment was combined with Nt-pro-BNP and transthoracic echocardiography, The median follow-up period was 16 months. Echocardiography and Nt-pro-BNP were performed at list 4-fold: at baseline, after cycle 6, and, at 3 and 12 months post-completion of treatment. Baseline echocardiography and Nt-pro-BNP were normal. After cycle 6, 28 clinically asymptomatic patients with decreased RV-PA coupling (<0.40 mmHg) and elevated Nt-pro-BNP ( median 225) were identified ( HF, Stage B ). EF was in the normal range. Mitral valve regurgitation more than mild was diagnosed in 19 patients. 28 patients were randomized 1:1 to conventional therapy with ACI and B-blockers (- statin group ,14 p.) and therapy with ACI and B-blockers and rosuvastatin 20 mg. ( + statin group,14 p)-for 12 months. Echocardiography was performed using a GE Vivid 7 ultrasound system according to the ASE's recommendations. Patients were investigated by the TAPSE/PAPs index. Results RV-PA coupling was higher in the +statin group by trend. Improvements in RV function, mitral regurgitation, and Nt-pro-BNP after 12 months of treatment with statin in addition to ACI and B-blocker, were observed in this study. Conclusion Our study demonstrates that the decrease of RV-PA coupling may be an early manifestation of anthracycline cardiotoxicity. Rosuvastatin favorably increases RV-PA coupling and improves RV function.