Patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) who were treated with anthracyclines were shown to have an increased risk of symptomatic heart failure, with the greatest risk coming within 1 year of exposure to treatment, according to a study published in JACC: Cardiooncology.1
In an effort to identify and mitigate that risk, the researchers also developed a risk score based on clinical and echocardiographic variables.
The study analyzed data from 450 patients with AML or ALL who were treated at the Hospital of the University of Pennsylvania between January 2004 and April 2018. Median follow-up was 16 months, and the cumulative anthracycline dose given was 183 ± 86 mg/m2. Forty patients (8.9%) developed symptomatic heart failure, with the median time until development being 10 months. Patients with AML had a higher incidence of heart failure than patients with ALL.
"While we are more effective at treating cancer, the improved survival rates have helped to unmask the cardiotoxic impact of some of the most common cancer therapies," said the study's corresponding author Marielle Scherrer-Crosbie, MD, PhD, director of the Cardiac Ultrasound Laboratory and a professor of cardiovascular medicine in the Perelman School of Medicine at the University of Pennsylvania, in a statement.
The risk score, which was developed alongside the study, utilized a number scoring scale of zero to 21, with points based on 6 examined variables of myocardial strain. The variables were as follows: a baseline global longitudinal strain (GLS) of greater than 15% (6 points), baseline left ventricle ejection fraction of less than 50%, pre-existing cardiovascular disease, and AML (4 points each), cumulative anthracycline dose of ≥250 mg/m2 (2 points) and age >60 years (1 point). The 1-year incidence of HF for low-risk groups (score of zero to 6) was 1.0%, moderate-risk groups (score of 7-13) 13.6% and high-risk groups (score of 14-21) was 35.0% (P < 0.001).
"Our hope, in creating this risk score system, is to help clinicians identify patients with the highest risk for potential cardiac damage, so they can more closely monitor the patients via a multidisciplinary approach,” said Scherrer-Crosbie.
The heart failure risk score was predictive of all-cause mortality as well (P < 0.001), however only the association of GLS with all-cause mortality turned out to be statistically significant.
There were some clear limitations to the study, notably that the score was developed in a single tertiary care center. The score has also not been validated prospectively or externally in another cohort. The researchers admitted that a large-scale prospective multicenter study would indeed substantially strengthen the risk score assessment.
"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," said lead author Yu Kang, MD, PhD, a post-doctoral research fellow at Penn, in the statement.
While calling for more studies to strengthen the validity of the risk score assessment, the authors expressed hope that further data and refinement would produce a scoring system that would prove a useful benefit to clinicians trying to balance the benefit of cancer treatment with its potential cardiac damage.
1. Kang Y, Assuncao BL, Denduluri S, et al. Symptomatic Heart Failure in Acute Leukemia Patients Treated with Anthracyclines. JACC: CardioOncology, 2019;1(2):208. doi: 10.1016/j.jaccao.2019.10.008.
2. Acute leukemia patients treated with common therapy have increased risk for heart failure [news release]. ScienceDaily. Published December 17, 2019. www.sciencedaily.com/releases/2019/12/191217141555.htm. Accessed January 8, 2020.