Over the last several years, the use of biomarkers in the diagnosis of patients with heart failure (HF) has skyrocketed. Natriuretic peptides are currently the most widely used biomarker in the diagnosis and prognosis of individuals with HF. Proenkephalin (PENK) activates delta-opioid receptors in cardiac tissue, resulting in a decreased myocardial contractility and heart rate. However, the goal of this meta-analysis is to evaluate the association between the PENK level at the time of admission and prognosis in patients with HF, such as all-cause mortality, rehospitalization, and decreasing renal function. High PENK levels have been associated with a worsened prognosis in patients with HF.

Background Proenkephalin (PENK), a novel biomarker, sequentially activates delta-opioid receptors in heart tissue causing reduced myocardial contractility, blood pressure, and heart rate. PENK has several prognostic abilities for patients with myocardial infarction, stroke, and impaired renal function. However, its prognostic value in heart failure patients is still inconclusive. Purpose To evaluate the association between plasma PENK level at the time of admission and all-cause mortality in patients with heart failure. Methods We collected studies from MEDLINE and EMBASE databases until January 2022 to perform a meta-analysis. High level of PENK is defined as plasma PENK level more than 99th percentile of the general population. Separated pooling hazard ratio (HR) for all-cause mortality among high and normal levels of PENK was performed using a random-effect model, generic inverse variance method of DerSimonian and Laird. Sources of heterogeneity including clinical and methodological variations were explored using a meta regression and subsequent subgroup analysis. Results A total of six observational studies composed of 6,929 patients with either acute heart failure or chronic heart failure were included in this analysis. There are five studies involving heart failure patients with both reduced ejection fraction and preserved ejection fraction and another one concerning those with only preserved ejection fraction. High level of PENK was found in 70.9% of patients. The high level of PENK compared with normal levels was associated with a higher prevalence of all-cause mortality with pooled HRs of 1.72 (95% CI, 1.62–1.84; I2=84%). The analyzed data were shown in the Figure 1. Conclusions This study demonstrates the association between high levels of PENK and all-cause mortality in heart failure patients. These findings suggest that the opioid system might be involved in deteriorating cardiovascular function in heart failure. Funding Acknowledgement Type of funding sources: None.

No abstract