Prediction of doxorubicin cardiotoxicity by early detection of subclinical right ventricular dysfunction

Abstract

Background: Doxorubicin remains one of the most common causes of cardiotoxicity in patients with lymphoma, leading to significant morbidity and mortality. Early decline in left ventricular (LV) ejection fraction predicts chemotherapy-induced cardiotoxicity and mortality, but limited data exist on doxorubicin-induced subclinical right ventricular (RV) dysfunction. We investigated dose-dependent subclinical doxorubicin-induced RV dysfunction in lymphoma patients. Methods: Thirty-five patients with adult lymphoma treated with doxorubicin were studied. All patients had normal baseline LV ejection fraction (LVEF > 55%), and no known cardiopulmonary disease. We studied the dosedependent effect of doxorubicin on RV strain by 2D speckle-tracking echocardiography (STE) using a vendorindependent software (TomTec). Images were analyzed offline by two independent observers blinded to the clinical characteristics of the study population. Baseline LVEF, RV fractional area change (RV FAC), RV free wall strain (RV FWS), and RV global longitudinal strain (RV GLS) were measured prior to chemotherapy initiation and compared with echo studies obtained at a 6-month follow-up interval. Patients served as their own controls. Comparisons between pre-and post-therapy were achieved using paired Student's t-tests or Chi-Square test. Results: The Interobserver Intraclass Correlation Coefficient for RV GLS, RV FAC and RV FWS, was 0.87, 0.81 and 0.79, respectively. The mean age was 51 ± 13 years, 40% women, 60% white. The mean cumulative doxorubicin dose was 239 ± 104 mg m − 2. There was there was significant decline in RV FAC (47.3 ± 4.4% vs. 43.7 ± 3.9%), RV FWS (− 24.9 ± 3.3 vs.-22.2 ± 2.9), and RV GLS (− 22.4 ± 4.1 vs.-20.6 ± 3.4) (all p < 0.01); but no significant decline in LVEF during the 6-month follow up (63.3 ± 6.2% vs. 61.6 ± 11.1%, p = 0.374). At cumulative doxorubicin dose ≥200 mg m − 2 we found a significant decline in RV FAC (47.0 ± 4.7% vs. 42.2 ± 3.1%, p < 0.01), RV FWS (− 24.6 ± 3.6 vs.-21.5 ± 2.4, p < 0.01), and RV GLS (− 22.3 ± 4.5 vs.-20.1 ± 2.9, p = 0.03). Conclusion: In this cohort of adult lymphoma patients, doxorubicin-based therapy was associated with subclinical RV dysfunction, but not LV dysfunction, at a cumulative dose ≥200 mg m − 2. Additional studies evaluating the longterm prognostic implications of RV dysfunction in this population are essential.

Cardiac magnetic resonance assessment of right ventricular remodeling after anthracycline therapy

“…Furthermore, subclinical differences in RV systolic EF and end-systolic volumes at baseline predicted LV systolic dysfunction after anthracyclines. These findings are consistent with recent reports that the RV may be at least as vulnerable to injury from anthracyclines as the LV, and early RV dysfunction may predict anthracycline-induced cardiotoxicity 16 , 17 . In addition, the reproducibility analysis for the RV ECV, demonstrated that our measurements were reliable, consistent and reproducible with ICC coefficients > 0.75 26 .…”

“…There are a paucity of studies applying such tissue characterization techniques to better understand the effects of anthracyclines on the RV. This is in contrast to several published studies on LV tissue remodeling after anthracyclines 2 – 5 ; additionally, several studies 16 , 17 have suggested that the RV may be more vulnerable to injury from anthracyclines, and early RV dysfunction may predict anthracycline-induced cardiotoxicity. We were specifically interested in understanding the effects of anthracyclines on the RV fibrosis, as measured by calculation of the extracellular volume (ECV), and on cardiomyocyte mass.…”

“…RV dysfunction may even represent an early warning sign of cardiotoxicity following anthracycline therapy. A previous study by Planek et al of lymphoma patients 16 with an average follow-up period of 6-months found that anthracycline therapy was associated with subclinical RV dysfunction, but not LV dysfunction, at a cumulative dose ≥ 200 mg/m 2 . In the present study LV systolic dysfunction was at a nadir around ~ 300 days allowing a more comprehensive evaluation of full impact of anthracyclines on ventricular function than in the study by Planek et al A novel finding from this study is that the RV ESVi at baseline is associated with the risk of LV systolic dysfunction after anthracycline therapy, suggesting that RV ESVi baseline status could help in risk stratification for patients undergoing anthracycline therapy.…”

Betanin and Allicin Ameliorate Adriamycin-Induced Cardiotoxicity in Rats by Ameliorating Cardiac Ischemia and Improving Antioxidant Efficiency

“…Betanin is a glycosidic water-soluble red pigment and is the bioactive constituent of red beetroot. [20][21][22][23] Its consumption has several health benefits, such as protection against ventricular disruption and ischemic injury [24,25]. Allicin (diallyl thiosulfate) is a major constituent of garlic [26][27][28][29].…”

The Utility of Advanced Cardiovascular Imaging in Cancer Patients—When, Why, How, and the Latest Developments

“…The data on RV strain in CTRCD suggests RV dysfunction frequently occurs with LV dysfunction and pertains a reduced recovery in LV function, though further studies are needed (26). Additionally, other studies suggest 2D and 3D RV strain deterioration occurs prior to LV parameters (27,28).…”