Importance of familial predisposition to heart failure to the risk of anthracycline related cardiotoxicity: A nationwide study.

BACKGROUND Anthracycline-based chemotherapy has improved the prognosis of various malignancies, but increases the long-term risk of heart failure (HF). Identification of patients at risk prior to treatment initiation is warranted. Therefore, the aim of this study was to evaluate if a familial predisposition to HF increases the risk of anthracycline related HF. METHODS Using nationwide Danish registries, all patients treated with anthracycline from 2004-16 were identified. The primary outcome was long-term HF risk. First-degree relatives were identified in the Danish Family Registry and exposure was defined as a first-degree biological relative with prior HF. Risk of HF was evaluated in a cumulative incidence function and the association in a multivariable Cox regression model. RESULTS A total of 11,651 patients (median age 49.1 years (IQR: 43.6-53.7), 12.2% male) were included after exclusion of 46 with pre-anthracycline HF. Median follow-up was 3.8 years (IQR 1.9-6.4). In the group with a first-degree relative with HF (n=1,608) 35 patients (2.2%) were diagnosed with HF vs. 133 (1.3%) in the group without a first-degree relative with HF (n=10,043), corresponding to incidence rates per 1,000 patient-years of 5.2 (CI:3.8-7.3) vs. 3.0 (CI:2.5-3.5). The cumulative incidence of HF after 10 years was higher in the first-degree relative group (3.2% vs 2.0%, p=0.004); adjusted hazard ratio 1.53 (CI:1.05-2.23, p=0.03). CONCLUSION In this nationwide register-based study having a first-degree relative with HF was associated with increased risk of anthracycline related HF, suggesting that attention towards family predisposition may be warranted when estimating the risk of anthracycline related cardiotoxicity.