Relationship of interleukin‐16 with different phenogroups in acute heart failure with preserved ejection fraction

Abstract

Aims

Interleukin‐16 (IL‐16) has been reported to mediate left ventricular myocardial fibrosis and stiffening in patients with heart failure with preserved ejection fraction (HFpEF). We sought to elucidate whether IL‐16 has a distinct impact on pathophysiology and prognosis across different subphenotypes of acute HFpEF.

Methods and results

We analysed 211 patients enrolled in a prospective multicentre registry of acute decompensated HFpEF for whom serum IL‐16 levels after stabilization were available (53% female, median age 81 [interquartile range 75–85] years). We divided this sub‐cohort into four phenogroups using our established clustering algorithm. The study endpoint was all‐cause death. Patients were subclassified into phenogroup 1 (‘rhythm trouble’ [n = 69]), phenogroup 2 (‘ventricular‐arterial uncoupling’ [n = 49]), phenogroup 3 (‘low output and systemic congestion’ [n = 41]), and phenogroup 4 (‘systemic failure’ [n = 52]). After a median follow‐up of 640 days, 38 patients had died. Among the four phenogroups, phenogroup 2 had the highest IL‐16 level. The IL‐16 level showed significant associations with indices of cardiac hypertrophy, diastolic dysfunction, and congestion only in phenogroup 2. Furthermore, the IL‐16 level had a significant predictive value for all‐cause death only in phenogroup 2 (C‐statistic 0.750, 95% confidence interval 0.606–0.863, P = 0.017), while there was no association between the IL‐16 level and the endpoint in the other phenogroups.

Conclusions

Our results indicated that the serum IL‐16 level had a significant association with indices that reflect the pathophysiology and prognosis of HFpEF in a specific phenogroup in acute HFpEF.