Is it possible to establish a threshold to define the inflammatory risk of acute heart failure patients? Letter regarding the article ‘Burst steroid therapy for acute heart failure: the CORTAHF randomized, open‐label, pilot trial’

I read with great interest the article by Cotter et al.,1 reporting results from the CORTAHF trial. In this open-label trial, patients admitted for a diagnosis of acute heart failure (AHF) and with high-sensitivity C-reactive protein (hsCRP) >20 mg/L were randomly assigned to receive oral, once-daily 40 mg prednisone for 7 days after hospitalization or usual care. The primary endpoint, i.e. reduction of hsCRP at day 7, was observed in both arms, but more evidently in the prednisone group; 90-day risk of worsening heart failure (HF), HF readmission or death however, resulted significantly lower in the prednisone group than controls (hazard ratio 0.31, 95% confidence interval 0.11–0.86, p = 0.016). As meticulously stated in the design paper of this trial,2 the choice of setting the threshold of hsCRP at 20 mg/L was based on previous evidence, which however resulted as sparse. In particular, in the ASCEND HF study,3 median hsCRP level at admission was about 12 mg/L, while, more recently, Miró et al.4 evaluated the effects of systemic steroids in AHF patients, highlighting greater benefits for those with CRP >40 mg/L. It goes without saying that in the acute setting, the higher the inflammatory burden is, the greater the effects of anti-inflammatory strategies may emerge. As well, with increasing levels of hsCRP, the risk of concomitant infectious diseases, where corticosteroids have shown advantages,5 appears concrete. On the other hand, more consistent knowledge comes from the ischaemic heart disease setting (both acute and chronic), in which randomized trials set the threshold of hsCRP at 2 mg/L to guide administration of anti-inflammatory therapies for secondary prevention.6 In sum, in the CORTAHF trial, the choice of such criteria may result as arbitrary and merits further clarifications to pave the way to future studies. The road to understand which is the optimal inflammatory biomarker to use in clinical trials (e.g. interleukin-6, hsCRP) and which threshold to establish to prescribe medications is still windy. After all, I appreciated the authors' contributions to this field of research, providing valuable insights for innovative strategies of treatment in AHF patients.