Temporal evolution of subclinical cardiac dysfunction during anticancer treatment in patients with breast cancer

Abstract

Subclinical cardiac dysfunction may develop early during anticancer treatment, preceding a decline in left ventricular ejection fraction (LVEF). While myocardial deformation imaging enables early detection of myocardial injury, the temporal evolution of diastolic dysfunction and left atrial (LA) remodeling during therapy remains incompletely characterized. To evaluate the 12-month temporal evolution of myocardial deformation, diastolic function, and LA volumetric and functional parameters in patients with breast cancer receiving anticancer treatment. This multicenter prospective study included 123 patients from four medical centers with HER2-positive breast cancer. All patients received standard-of-care anticancer therapy, including anthracycline-based chemotherapy followed by trastuzumab. Transthoracic echocardiography was performed at baseline and at 3, 6, 9, and 12 months of follow-up. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were assessed, along with tissue Doppler e′ velocities (septal, lateral), average E/e′. Left atrial remodeling and function were assessed using indexed maximal and minimal LA volumes (LAVmax, LAVmin) and total LA emptying function (LAEF).Data are presented as mean ± standard deviation. Changes over time were assessed using repeated-measures ANOVA; a two-sided p-value <0.05 was considered statistically significant. LVEF remained within the normal range throughout follow-up (62 ± 4% at baseline; 59 ± 5% at 12 months). GLS progressively deteriorated from −20.2 ± 1.8% to −17.1 ± 2.0% at 6 months and −15.7 ± 2.3% at 12 months (relative reduction of 15% and 22%, respectively). Diastolic indices worsened with septal e′ decreasing from 8.1 ± 1.4 to 5.9 ± 1.2 cm/s and lateral e′ from 11.2 ± 1.8 to 8.1 ± 1.5 cm/s, while average E/e′ increased from 10.1 ± 2.1 to 15.6 ± 3.0 at 12 months, indicating progressively elevated left ventricular filling pressures. Of particular interest, significant involvement of the LA was observed. Indexed LAVmin increased from 10.4 ± 4.2 to 18.1 ± 6.3 ml/m², preceding enlargement of LAVmax from 28.3 ± 6 to 38 ± 8.1 ml/m². LAEF progressively declined from 62% at baseline to 46% at 12 months, reflecting progressive atrial functional impairment and remodeling. Anticancer treatment is associated with a structured temporal continuum of subclinical cardiac dysfunction, in which early impairment of myocardial deformation is followed by progressive alterations in diastolic mechanics and left atrial structure and function, despite preserved left ventricular ejection fraction. Serial echocardiographic assessment enables early identification of cardiotoxicity and supports timely risk stratification before overt systolic dysfunction develops.