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

Circ Cardiovasc Imaging. 2014 Nov;7(6):872-9. doi: 10.1161/CIRCIMAGING.114.002217. Epub 2014 Oct 1.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anthracyclines / adverse effects*
  • Antibiotics, Antineoplastic / adverse effects*
  • Antibodies, Monoclonal / adverse effects*
  • Breast Neoplasms / drug therapy*
  • Edema, Cardiac / chemically induced
  • Edema, Cardiac / pathology
  • Edema, Cardiac / physiopathology
  • Female
  • Heart Ventricles / drug effects*
  • Heart Ventricles / pathology
  • Heart Ventricles / physiopathology
  • Hematologic Neoplasms / drug therapy*
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging*
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Stroke Volume / drug effects*
  • Time Factors
  • Tubulin Modulators / adverse effects*
  • Ventricular Dysfunction, Left / chemically induced*
  • Ventricular Dysfunction, Left / pathology
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Function, Left / drug effects*

Substances

  • Anthracyclines
  • Antibiotics, Antineoplastic
  • Antibodies, Monoclonal
  • Tubulin Modulators