Association between cardiovascular risk factors and cancer therapy-related cardiac dysfunction in patients with breast cancer
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.

Background
Cancer therapy-related cardiac dysfunction (CTRCD) is one of the major complications being reported in breast cancer (BC) patients. The clinical relevance of CTRCD and its cardiovascular risk factors (CVRF) remains unclear.

Purpose
Our aim was to investigate the impact of baseline CVRF on ventricular systolic function in BC patients.

Methods
Retrospective study of patients with BC treated with anthracyclines (A) and/or trastuzumab between Jan 2017 and Dec 2018 who underwent a transthoracic echocardiography (TTE) before, during, and after chemotherapy. CTRCD is defined as a reduction of LVEF &gt;10% to a value &lt;50% or as a relative reduction of GLS &gt;15%.

Results
We included 128 females 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%). LVEF at baseline was 64,7 ± 5,7%.
At baseline, hypertension was present in 34,4% (44), dyslipidaemia in 29,9% (38), overweight (BMI: 25-30kg/m2) in 33,6% (43), obesity (BMI: &gt;30kg/m2) in 28,1% (36), diabetes in 13 (10,2%) and smoker status in 11 (8,6%). No one had ischemic heart disease.
During a mean follow-up of 38 months, 35 (27%) patients developed CTRCD from which 9 (7%) suffered clinical heart failure.
After multivariate analysis, in the group treated with T (with or without A), the BMI &gt;25 kg/m2 was the only CVRF associated to the development of CTRCD (p &lt; 0,01). In the group treated with A, no CVRF was associated with CTRCD. During follow-up, BMI &gt;25kg/m2 was not associated to a lower survival (log-rank p test = 0.627).
In the baseline TTE did not occur statistically significant differences between the groups according to the absence or presence of CVRF. Nonetheless, some statistically significant differences occurred during follow-up. In hypertensive patients, treated with T, the TTE at 2 years of follow-up had a significant decrease in LVEF (5,9 ±2,8; p = 0,047) compared to non-hypertensive patients. In diabetic patients, treated with A, there was a significant decrease in tricuspid annular systolic velocity (S") in the TTE after chemotherapy (2,8 ±1,4; P = 0,049) compared to non-diabetic. The group of patients with dyslipidaemia treated with A had a significant decrease in GLS in the TTE after chemotherapy (1,5 ± 0,7; p = 0,037) compared to patients without dyslipidaemia; The same group treated with T (without A) revealed a significant decrease in S’ in the TTE during T therapy (5,2 ± 1,6; p = 0,034). The group of patients with BMI &gt;25 kg/m2 treated with T (without A) showed a significant decrease in the GLS during T therapy (5,1 ± 1,6; p = 0,021) and in the LVEF at 2 years of follow-up (15,3 ± 5,7; p = 0,036) compared to patients with BMI &lt;25 kg/m2.

Conclusions
In our cohort, a high BMI was an independent risk factor for CTRCD among patients treated with T. This finding is in agreement with literature data. These results should encourage further research into the mechanisms linking overweight/obesity to CTRCD.