High sensitivity C-reactive protein: a biomarker for heart failure in children with univentricular heart disease

Alexander Lowenthal,¹ Luz Natal-Hernandez,¹ Shiri Lowenthal,¹ Nancy K Hills,² Harold S Bernstein<sup>1,3,4

1</sup>Department of Pediatrics, ²Clinical and Translational Science Institute, ³Cardiovascular Research Institute, ⁴Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, CA, USA

Abstract: Children with univentricular congenital heart disease are at increased risk for developing heart failure. However, detecting early heart failure in these patients is especially difficult because few objective measures have been validated in this cohort. The aim of this study is to determine the usefulness of high sensitivity C-reactive protein (hsCRP) as a biomarker for detecting heart failure in univentricular heart disease patients, and to define the impact of univentricular morphology and stage of palliation on its utility. A cross-sectional observational study of children with univentricular congenital heart disease aged 1 month to 7 years was conducted. The presence of heart failure was defined as a Ross score > 2. The association of hsCRP with heart failure was assessed using logistic regression and receiver operating characteristic curves. Of the 50 included children, 16 (32%) had clinical heart failure. A doubling of hsCRP resulted in a 0.31 unit increase in Ross score (95% confidence interval: –0.07, 0.56; P = 0.01) with a c-statistic of 68%. When stratified by ventricular morphology, the left univentricular morphology group exceeded the threshold of ≥75% (c-statistic = 81%) as did those at stage II of palliation (c-statistic = 85%). A cut point of ≥0.8 mg/mL correctly classified 75% of patients with left univentricular morphology, and 73% of patients regardless of morphology at stage II of palliation. From these results, we conclude that hsCRP is a useful biomarker of clinical heart failure in univentricular patients with left ventricular morphology at all stages of surgical palliation, and in all univentricular patients at stage II of palliation.

Keywords: congenital heart disease, single ventricle, heart failure, biomarker, high sensitivity C-reactive protein