Whole-Heart Changes During Cancer Therapy and Their Potential Relevance in Women With Breast Cancer

The simultaneous impact of breast cancer therapy on the heart beyond the left ventricle and its prognostic implications are not understood. The objective of this study was to determine how breast cancer therapy affects all four cardiac chambers, whether patient clusters based on similarities in changes in multichamber measures have different prognosis, and how these patient clusters could be differentiated.

In a secondary analysis of a prospectively recruited cohort of women with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving anthracycline and trastuzumab, echocardiography was performed before treatment and every 3 months (six studies) to assess cardiac chamber size and function (volumes, ejection fraction, and longitudinal strain) of all four cardiac chambers (EchoInsight). Prognostic measures were cardiovascular magnetic resonance-defined cancer therapy-related cardiac dysfunction (CTRCD), and peak oxygen uptake. Network partition analysis was conducted to identify patterns in multichamber temporal changes, and a random forest algorithm was used to evaluate the relative predictive importance of the chamber measures for CTRCD.

Among 136 women (mean age, 51.1 ± 9.2 years), three main related patterns of temporal changes in echocardiographic measures were identified during treatment: (1) worsening function of all four chambers, (2) left chamber remodeling, and (3) right chamber remodeling. On the basis of similarities in multichamber changes, three patient clusters were identified. When further characterized, the three clusters differed in their CTRCD incidence (3%, 7%, and 27%, P = .004) and percentage predicted peak oxygen uptake after trastuzumab therapy (92.1% [interquartile range, 76.9%-100.5%], 82.5% [interquartile range, 70.2%-92.7%], and 75.3% [interquartile range, 66.4%-91.2%], respectively, P = .040). The highest risk group could be identified by early large simultaneous worsening of multichamber function. Non-left ventricular (LV) parameters had similar or higher relative contributions to CTRCD prediction compared with LV parameters.

In this hypothesis-generating study, breast cancer therapy was observed to affect the size and function of all four cardiac chambers. Monitoring multichamber function may improve CTRCD risk assessment beyond LV evaluation alone. This approach may be particularly attractive for future artificial intelligence-based echocardiographic algorithms.