Longitudinal assessment of concurrent changes in left ventricular ejection fraction and left ventricular myocardial tissue characteristics after administration of cardiotoxic chemotherapies using T1-weighted and T2-weighted cardiovascular magnetic resonance

Abstract

Background: In a murine anthracycline-related cardiotoxicity model, increases in cardiovascular magnetic resonance myocardial contrast-enhanced T1-weighted signal intensity are associated with myocellular injury and decreases with left ventricular ejection fraction. We sought to determine whether T1- and T2-weighted measures of signal intensity associate with decreases in left ventricular ejection fraction in human subjects receiving potentially cardiotoxic chemotherapy.

Methods and results: In 65 individuals with breast cancer (n=51) or a hematologic malignancy (n=14), we measured left ventricular volumes, ejection fraction, and contrast-enhanced T1-weighted and T2-weighted signal intensity before and 3 months after initiating potentially cardiotoxic chemotherapy using blinded, unpaired analysis of cardiovascular magnetic resonance images. Participants were aged 51 ± 12 years, of whom 55% received an anthracycline, 38% received a monoclonal antibody, and 6% received an antimicrotubule agent. Overall, left ventricular ejection fraction decreased from 57 ± 6% to 54 ± 7% (P<0.001) because of an increase in end-systolic volume (P<0.05). T1-weighted signal intensities also increased from 14.1 ± 5.1 to 15.9 ± 6.8 (P<0.05), with baseline values trending higher among individuals who received chemotherapy before study enrollment (P=0.06). Changes in T1-weighted signal intensity did not differ within the 17 LV myocardial segments (P=0.97). Myocardial edema quantified from T2-weighted images did not change significantly after 3 months (P=0.70).

Conclusions: Concordant with previous animal studies, cardiovascular magnetic resonance measures of contrast-enhanced T1-weighted signal intensity occur commensurate with small but significant left ventricular ejection fraction declines 3 months after the receipt of potentially cardiotoxic chemotherapy. These data indicate that changes in T1-weighted signal intensity may serve as an early marker of subclinical injury related to the administration of potentially cardiotoxic chemotherapy in human subjects.

Keywords: anthracyclines; cardiotoxicity; chemotherapy; left ventricular function; magnetic resonance imaging.

Figure 1

Panel A and B: Segmentation of endocardial (green) and epicardial (red) borders using splines for extraction of myocardial voxels in CMR analysis. Panel C: AHA 17-segment models for one participant at baseline and three months after chemotherapy demonstrating diffuse increases in contrast-enhanced T1-weighted signal intensity across the myocardium commensurate with a large LVEF drop.

Figure 2

LVEF dropped from 57±1% to 54±1% in the three months following chemotherapy exposure (blue solid line, p<0.001). Concurrently, contrast-enhanced T1-weighted signal intensity (LGE-SI) increased from 14.1±0.6 to 15.9±0.8 in the study population (red dashed line, p<0.05).

Figure 3

Study participants without prior chemotherapy exposure (left) exhibited both significantly increased contrast-enhanced T1-weighted signal intensity (LGE-SI, red, right axis) and decreased LVEF (blue, left axis) three months after chemotherapy initiation. Conversely, in those with prior chemotherapy exposure (right), LGE-SI was elevated at rest and did not increase after additional chemotherapy even though LVEF decreased.