Cancer therapeutics-related cardiac dysfunction: what is the role of cardioprotective medication?
Authors: Tinoco M , Dias G , Cardoso F , Pereira T , Lima B , Oliveira L , Von Hafe P , Azevedo O , Leite S , Lourenco A 
Published: February 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Cancer therapy-related cardiac dysfunction (CTRCD) is one of the major complications being reported in patients with breast cancer (BC) under chemotherapy, in particular with anthracyclines (A) or trastuzumab (T). Guidelines recommend regular left ventricular ejection fraction (LVEF) assessments and CTRCD management with cardioprotective medication (CPM). However, while secondary prevention has already entered clinical practice, primary prevention is still in the research domain.

Purpose
Our aim was to evaluate the role of CPM and the risk of CTRCD in BC patients.

Methods
Retrospective study of BC patients treated with A and/or T between Jan 2017 and Dec 2018 who underwent a transthoracic echocardiography (TTE) before, during, and after chemotherapy. Patients with baseline LVEF &lt;50% were excluded. CTRCD is defined as reduction of EF &gt;10% to a value &lt;50% or as relative reduction of global longitudinal strain (GLS) &gt;15%. As CPM we considered angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blocker (ARB) and beta-blockers (BB).

Results
We included 128 patients, all female with median age of 54 ± 11 years-old, treated with A (78; 60.9%), T (14; 10.9%) or A followed by T (36; 28.1%).
At baseline, mean LVEF was 64,7 ± 5,7% and mean GLS was -20,8 ± 2,3.
During a mean follow-up of 38 months, 35 (27%) patients developed CTRCD with a higher prevalence in patients who took A followed by T (18; 14%), 9 (7%) presented with clinical heart failure, 1 (1%) needed hospitalization, 5 (4%) needed to temporarily suspend treatment and 3 (2%) needed to definitely stop treatment. ACEI/ARB therapy was initiated in 12 (34%) and BB therapy was initiated in 10 (29%). Twenty-one (60%) of CTRCD patients recovered. CPM initiation after CTRCD was not associated with a significant higher rate of cardiac function recovery (p = 0,682).
When comparing patients already medicated with CPM before cancer treatment (39; 30,5%) to those naïve of CPM, the first group presented a lower incidence of CTRCD (7% vs 20%) but it was not statistically significant (p = 0,473).
In patients treated with T or A + T, the group of patients treated with CPM before cancer treatment did not present a significantly lower incidence of CTRCD (p = 0,449) compared to patients CPM naïve. Nonetheless, there was a significant higher LVEF in the TTE during T therapy, after chemotherapy and at 2 years of follow-up (P &lt;0,05) in patients treated with CPM before cancer treatment compared to patients CPM naïve.
In patients treated with A (without T) there was no statistically significant difference between the two groups.

Conclusion
In our study, pre-treatment with CPM was associated with a significant higher LVEF in patients treated with T but no significant association was found with respect to the occurrence of CTRCD. CPM initiation after CTRCD was not associated with a statistically significant cardiac function recovery.