Long-term cardiovascular consequences of cancer therapy-related cardiac dysfunction: insights from ventricular-arterial coupling and myocardial work

Anthony F Yu; Jessica M Scott; Jessica Flynn; Chaya S Moskowitz; Chau T Dang; Lee W Jones; Richard M Steingart; Jennifer E Liu

doi:10.1093/ehjimp/qyaf072

Long-term cardiovascular consequences of cancer therapy-related cardiac dysfunction: insights from ventricular-arterial coupling and myocardial work

Eur Heart J Imaging Methods Pract. 2025 Jun 3;3(1):qyaf072. doi: 10.1093/ehjimp/qyaf072. eCollection 2025 Jan.

Authors

Anthony F Yu^{1

2}, Jessica M Scott^{1

2}, Jessica Flynn³, Chaya S Moskowitz³, Chau T Dang^{1

2}, Lee W Jones^{1

2}, Richard M Steingart^{1

2}, Jennifer E Liu^{1

2}

Affiliations

¹ Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
² Department of Medicine, Weill Cornell Medical College, 530 East 70th Street, New York, NY 10021, USA.
³ Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.

Abstract

Aims: Ventricular-arterial (VA) coupling and myocardial work can assess the interaction between the left ventricle and the arterial system and provide insight into cancer-therapy-related cardiac dysfunction (CTRCD). This study assessed the relationship between VA coupling and myocardial work indices with CTRCD in breast cancer (BC) survivors.

Methods and results: In this cross-sectional case-control study, 42 human epidermal growth factor receptor 2-positive BC survivors [22 with a history of CTRCD (TOX), 20 without CTRCD (NOTOX)] and 15 age-matched healthy controls (HC) prospectively underwent echocardiography and cardiopulmonary exercise testing. VA coupling measures were arterial elastance (Ea) and end-systolic elastance (Ees), with increased Ea/Ees indicating ventricular-arterial uncoupling. Myocardial work measures included global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). Linear regression models assessed associations between VA coupling and myocardial work indices with cardiorespiratory fitness, measured by peak oxygen consumption (VO_2peak). Ea and Ea/Ees were elevated in TOX [Ea: 2.00 (interquartile range (IQR), 1.83-2.25) mmHg/mL, P = 0.006; Ea/Ees: 1.48 (1.05-1.66), P = 0.002], but not NOTOX [Ea: 1.68 (1.36-1.95) mmHg/mL, P = 0.8]; [Ea/Ees: 1.15 (1.03-1.28), P = 0.2] participants, compared to HC [Ea, 1.65 (1.50-1.73) mmHg/mL; Ea/Ees, 1.07 (0.89-1.19)]. GWW was increased and GWE was reduced in TOX [GWW: 86 (59-132) mmHg%, P = 0.009; GWE: 95 (94-96) %, P = 0.003] but not NOTOX [GWW: 64 (44-94) mmHg%, P = 0.3; GWE: 96 (96-97) %, P = 0.003] participants, compared to HC [GWW: 46 (38-60) mmHg%; GWE: 97 (97-98) %]. Higher Ea (β=-0.16, P = 0.005) was associated with impaired VO_2peak in BC survivors.

Conclusion: CTRCD is associated with VA uncoupling in BC survivors, the mechanism of which may be increased arterial load. Studies to evaluate whether reducing arterial load can mitigate VA uncoupling are needed.

Keywords: Echocardiotoxicity; cardio-oncology; myocardial work; ventricular–arterial coupling.