Abstract

Background

Trastuzumab (TZ) is widely used for his key role in HER2 positive breast cancer. However, the most concerning cardiovascular complication is cardiotoxicity. Many studies have highlighted the importance of screening for subclinical myocardial dysfunction using left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). However, there are only few studies investigating a possible atrial damage.

Purpose

Aim of this study was to analyze the modification peak atrial systolic longitudinal strain (PALS) in patients undergoing therapy with TZ in a follow-up period of 12 months. The fluctuation of left atrial function parameters under chemotherapy was evaluated focusing the attention on those patients who developed cancer therapy–related cardiac dysfunction (CTRCD).

Methods

116 women affected by breast cancer treated with TZ were enrolled. Each patient underwent a complete echocardiography at baseline and every 3 months.

Exclusion criteria were poor quality imaging and lack of a complete follow up with consequent missing data.

CTRCD was defined as a decrease in the left ventricular ejection fraction of >10 percentage points to a value <53% at any time of follow-up. 2D-Speckle tracking analysis was performed at baseline and at each examination using Tomtec software to analyze both atrial and left ventricular function. Trends of GLS, and PALS during 12 months-follow up periods were analyzed. Additionally, we explored if diabetes and renal impairment were associated with more prevalent atrial subclinical disfunction as demonstrated in previous studies.

Results

A total of 10 patients (9%) developed cancer therapy–related cardiac dysfunction. A significant reduction in GLS compared to the baseline was observed during the whole follow-up (p=0.05), starting in the first six months of treatment (-21 ± 2% vs -17 ± 2%, p= 0.021). Interestingly, PALS showed a similar trend with a significant decrease during the whole 12 months-follow up (p=0.012), starting in the first 3 months (45 ± 9% vs 35 ± 8%, p=0.001).

6 patients presented a diagnosis of diabetes at baseline, and presented lower PALS compared to the non-diabetic counterpart (38± 10% vs 49 ± 12% p=0.03).

2 patients presented a significant renal impairment (eGFR ≤30 ml/min). Similarly, these patients presented a lower PALS at baseline (32 ± 7% and 48 ± 7%; p=0.055).

Conclusions

In patients treated with Trastuzumab the development of left atrial impairment is frequent and PALS modifications seem to precede GLS variations in patients with CTRCD, suggesting a possible cardiotoxic effect of such therapy on both atrial and left ventricular myocardium and physiology.

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