Circulating SERPINA3 improves prognostic stratification in patients with a de novo or worsened heart failure

Aims We investigated the prognostic relevance of serpin peptidase inhibitor, clade A member 3 (SERPINA3) in patients admitted with a de novo or worsened heart failure (HF). Methods and results In the first stage, 83 HF-related left ventricular (LV) transcripts were examined in patients with congestive cardiomyopathy (CCMP, n = 44) who died within 5 years and compared with age-matched and haemodynamically matched CCMP survivors (n = 39) and controls with normal LV function (n = 17). Among 14 differentially expressed transcripts, myocardial gene and circulating SERPINA3 levels were up-regulated in non-survivors vs. survivors (2.40 +/- 3.66 vs. 0.36 +/- 0.22 units, P < 0.01 and 334.7 +/- 138.7 vs. 228.2 +/- 83.1 mu g/mL, P < 0.01, respectively). While no significant transmyocardial gradient was detected, cytokine stimulation of human endothelial cells induced SERPINA3 secretion. In an independent validation cohort with a de novo or worsened HF (n = 387), circulating SERPINA3 levels > 316 mu g/mL were associated with increased all-cause mortality {hazard ratio [HR] [95% confidence interval (CI)]: 2.4 [1.5-3.9], P = 0.0002} and its composite with unplanned cardiovascular readmission [HR (95% CI): 2.0 (1.2-3.3), P = 0.004]. Patients with elevated SERPINA3 levels and elevated either N-terminal pro brain natriuretic peptide or ST2 showed worse freedom from both endpoints. In a multivariate analysis, including established clinical risk factors, SERPINA3 remained independent predictor of all-cause mortality together with age, gender, ST2, glomerular filtration, and pulmonary capillary wedge pressure. Conclusion In patients with a de novo or worsened HF, increased SERPINA3 levels > 316 mu g/mL are associated with increased mortality or unplanned cardiac readmission. Elevated SERPINA3 levels on top of established clinical predictors appear to identify a subgroup of HF patients at higher mortality risk. Prospective studies should further validate its value in prognostic stratification of HF.

Automated summary

The study revealed that elevated levels of circulating SERPINA3 in heart failure patients may be associated with increased mortality or unplanned cardiac readmission, especially in patients with elevated levels of SERPINA3 along with other markers.