Risk of Heart Failure Greater in Patients With AML, ALL on Anthracyclines

Owing to scarce knowledge regarding the connection between acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and risk of heart failure (HF) from anthracycline use in chemotherapy, researchers from the Hospital of the University of Pennsylvania (HUP) wanted to develop a risk score to help oncologists stratify their highest-risk patients. Such a score, they believe, will enable treatment to be tailored more to the individual patient. Their study was published in a recent issue of JACC: CardioOncology.

Anthracyclines are a standard therapy to treat acute cases of leukemia, and they have led to increased survival rates in these patients to the tune of 1% each year from 2006 to 2015, according to a release on the study results. However, the treatment is extremely toxic, and that combined with longer patient survival has focused attention on the cardiotoxic effects of this class of drugs.

The researchers analyzed data from a group of 450 patients treated at HUP between January 2004 and April 2018, based on 6 risk factors, assigning a point value to each to classify patients as low (0-6 points), moderate (7-13 points), or high risk (14-21 points):

1. Baseline global longitudinal strain (GLS) greater than —15% (6 points)
2. Baseline left ventricular ejection fraction (LVEF) less than 50% (4 points)
3. Preexisting heart disease (4 points)
4. AML (4 points)
5. Cumulative anthracycline dose of at least 250 mg/m² (2 points)
6. Age older than 60 years (1 point)

Follow-up began concurrent with start of anthracycline therapy and continued until death, event of interest (undefined in the study), or study end (June 30, 2018). Patients were excluded if an echocardiogram was not performed before starting anthracycline treatment, if the result was a poor-quality image, or there was no follow-up.

Almost 9.0% (40/450) of patients developed HF an average of 10 months after therapy initiation (range, 1-76 months), and 47.8% (215/450) died from noncardiac causes. These patients also had lower LVEF, and their GLS was worse, which signified greater heart impairment. Close to 71.0% (318/450) were considered low risk; 24.9% (112/45), moderate risk; and 4.4% (20/450), high risk. The corresponding estimated rates of HF were 1.0%, 13.6%, and 35.0%, and more women fell into the low- (1.3% vs 0.8%) and high-risk (38.8% vs 33.7%) groups.

When broken down by acute leukemia subtype, HF occurred more often in patients with AML than ALL: 11.6% compared with 3.4%. This association remained after adjusting for older age and cumulative anthracycline dose.

What could be the reasons for these results? The authors believe 3 factors that accompany leukemia could be to blame: the possibility of high cytokine release, malignant cancer cells infiltrating the heart, or ischemic cardiac disease. Plus, reduced LVEF could mean less aggressive cancer treatment.

Despite study limitations that included possible selection bias (because patients with lack of follow-up were excluded) and lack of external or prospective risk score validation, the authors are calling for additional studies to explore the use of their risk scoring system.

“While this is a significant step toward identifying patient risk for heart failure, additional studies are needed to determine the effectiveness of such a risk score in clinical practice,” stated the study’s lead author Yu Kang, MD, PhD, a postdoctoral research fellow at University of Pennsylvania.

Reference

Kang Y, Assuncao BL, Denduluri S, et al. Symptomatic heart failure in acute leukemia patients treated with anthracyclines. J Am Coll Cardiol CardioOnc. In press.