Longitudinal assessment of right ventricular structure and function by cardiovascular magnetic resonance in breast cancer patients treated with trastuzumab: a prospective observational study

Abstract

Background: There are limited data on the effects of trastuzumab on the right ventricle (RV). Therefore, we sought to evaluate the temporal changes in right ventricular (RV) structure and function as measured by cardiovascular magnetic resonance (CMR), and their relationship with left ventricular (LV) structure and function in breast cancer patients treated with trastuzumab.

Methods: Prospective, longitudinal, observational study involving 41 women with HER2+ breast cancer who underwent serial CMR at baseline, 6, 12, and 18 months after initiation of trastuzumab. A single blinded observer measured RV parameters on de-identified CMRs in a random order. Linear mixed models were used to investigate temporal changes in RV parameters.

Results: Of the 41 women (age 52 ± 11 years), only one patient experienced trastuzumab-induced cardiotoxicity. Compared to baseline, there were small but significant increases in the RV end-diastolic volume at 6 months (p = 0.002) and RV end-systolic volume at 6 and 12 months (p < 0.001 for both), but not at 18 months (p = 0.82 and 0.13 respectively). RV ejection fraction (RVEF), when compared to baseline (58.3%, 95% CI 57.1-59.5%), showed corresponding decreases at 6 months (53.9%, 95% CI 52.5-55.4%, p < 0.001) and 12 months (55%, 95% CI 53.8-56.2%, p < 0.001) that recovered at 18 months (56.6%, 95% CI 55.1-58.0%, p = 0.08). Although the temporal pattern of changes in LVEF and RVEF were similar, there was no significant correlation between RVEF and LVEF at baseline (r = 0.29, p = 0.07) or between their changes at 6 months (r = 0.24, p = 0.17).

Conclusion: In patients receiving trastuzumab without overt cardiotoxicity, there is a subtle but significant deleterious effect on RV structure and function that recover at 18 months, which can be detected by CMR. Furthermore, monitoring of LVEF alone may not be sufficient in detecting early RV injury. These novel findings provide further support for CMR in monitoring early cardiotoxicity.

Trial registration: ClinicalTrials.gov Identifier: NCT01022086 . Date of registration: November 27, 2009.

Keywords: Cardiotoxicity; Cardiovascular magnetic resonance; Right ventricle; Trastuzumab.

Figures

Fig. 1

Longitudinal measurements of RVEDV over 18 months. There were significant changes in RVEDV over time (p = 0.004). By Sidak-adjusted pairwise comparisons with the baseline, the mean RVEDV showed a small but significant increase at 6 months (p = 0.002), that was no longer significant at 18 months (p = 0.82). Data shown as mean and 95% confidence intervals (vertical bars)

Fig. 2

Longitudinal measurements of RVESV over 18 months. There were significant changes in RVESV over time (p < 0.001). By Sidak-adjusted pairwise comparisons with the baseline, the mean RVESV showed a small but significant increase at 6 and 12 months (both p < 0.001), that was no longer significant at 18 months (p = 0.14). Data shown as mean and 95% confidence intervals (vertical bars)

Fig. 3

Longitudinal measurements of RVEF over 18 months. There were significant changes in RVEF over time (p < 0.001). By Sidak-adjusted pairwise comparisons with the baseline, the mean RVEF showed a small but significant decrease at 6 and 12 months (p < 0.001 for both), that was no longer significant at 18 months (p = 0.08). Data shown as mean and 95% confidence intervals (vertical bars)

Fig. 4

Relationship between LVEF and RVEF over 18 months. The changes in LVEF and RVEF paralleled each other over time. Both the LVEF and RVEF showed significant changes at 6 and 12 months that recover at 18 months

Fig. 5

Relationship between changes in RVEF and LVEF over 6 months