Elevated Troponin Levels Associated With Trastuzumab-Related Cardiac Dysfunction

In patients with HER2-positive breast cancer undergoing trastuzumab therapy, elevated troponin I or T before the treatment is associated with an increased risk of trastuzumab-related cardiac dysfunction (TRCD), according to a new study.

TRCD is different from anthracycline-induced cardiotoxicity; TRCD is mostly reversible, and is generally assessed by monitoring left ventricular ejection fraction (LVEF). However, this can neither detect early TRCD or predict deterioration of cardiac function, according to study authors led by Evandro de Azambuja, MD, PhD, of the Jules Bordet Institute in Brussels.

The new study tested whether certain cardiac markers might fill that gap. It included 452 patients who were enrolled in the HERA (Herceptin Adjuvant) study, and examined whether troponins I and T along with N­-terminal prohormone of brain natriuretic peptide (NT-proBNP) was associated with cardiac endpoints including significant LVEF drop, congestive heart failure class III or IV, or death due to definite or probable cardiac cause. The results were published online ahead of print in the Journal of Clinical Oncology.

A total of 56 of 412 evaluable patients had elevated troponin I (> 40 ng/L; 13.6%) at baseline, and 101 of 407 had elevated troponin T (> 14 ng/L; 24.8%). These elevations were associated with occurrence of a significant drop in LVEF, for troponin I, the hazard ratio (HR) on a univariate analysis for LVEF drop was 4.52 (95% CI, 2.45–8.35; P < .001); for troponin T, the HR was 3.57 (95% CI, 1.95–6.55; P < .001).

There is no generally accepted cutoff value for elevation of NT-proBNP, so the investigators modeled whether incremental increases in the marker were associated with LVEF drop. For each increase of 1 ng/dL of NT-proBNP, the HR was 1.03 (95% CI, 1.02–1.04; P < .001). They noted that this should be considered clinically meaningful.

Only three patients in the study experienced a cardiac endpoint; one of these had missing baseline marker values, and the other two had increased BNP and troponin levels at baseline.

“Our study represents the largest effort to identify markers for TRCD within the context of a randomized adjuvant trastuzumab trial, confirming that increased troponin I is associated with [increased TRCD risk] in women receiving adjuvant trastuzumab,” the authors concluded, adding that this is the first time elevated troponin T was shown to be associated as well. “Further studies for identification of predictive markers of TRCD are warranted.”