# Clinical Value of Bioactive Adrenomedullin and Proenkephalin A in Patients with Left Ventricular Assist Devices: An Observational Study

## TL;DR

This study shows that two biomarkers, penKid and bio-ADM, can predict complications like kidney injury and heart failure in patients after LVAD surgery, improving risk prediction when added to existing scores.

## Contribution

The study demonstrates that penKid and bio-ADM are novel predictors of post-LVAD complications when combined with established risk scores.

## Key findings

- Preoperative penKid predicted postoperative AKI and 30-day mortality in LVAD patients.
- Bio-ADM was the only predictor of postoperative right heart failure and rehospitalization.
- Adding biomarkers to clinical scores significantly improved prediction accuracy (AUC up to 0.98).

## Abstract

Background/Objectives: In the context of acute heart failure, proenkephalin A (penKid) has emerged as a prognostic marker for acute kidney injury (AKI), whereas bioactive adrenomedullin (bio-ADM) has been identified as a significant biomarker linked to shock and organ dysfunction. This raises the question of whether they can serve as predictors of postoperative complications in patients receiving left ventricular assist devices (LVADs). Methods: This observational study prospectively enrolled patients who had received LVAD implantation. Routine laboratory values as well as plasma levels of penKid and bio-ADM were assessed at four time intervals, spanning from preinduction of anesthesia to 48 h post surgery. Clinical data, the HeartMate 3-risk-score (HM3RS), HeartMateII-risk-score (HMRS), Michigan-right-heart-failure risk score (MRHFS), Euromacs-RHFS (EURORHFS), and kidney failure risk score (KFR) were calculated. Multivariate logistic regression and receiver operating characteristic (ROC) analysis were performed. We entered the biomarkers with the established risk scores into the models. Results: In 20 patients who had undergone LVAD implantation, preoperative penKid level was a predictor of postoperative AKI (OR: 1.05, 95%-CI: 1.0–1.09; p = 0.049) and 30-day mortality (OR: 1.01, 95%-CI: 1.0–1.02; p = 0.033). Bio-ADM was the only predictor of postoperative right heart failure (RHF) (OR: 1.11, 95%-CI: 1.01–1.23; p = 0.034) and rehospitalization (OR: 1.06, 95%-CI: 1.0–1.13; p = 0.047). In the ROC analysis, bio-ADM, as a predictor of post-LVAD RHF, had an area under the curve (AUC) of 0.88. When bio-ADM was added to the accepted clinical scores for post-LVAD RHF prediction (CRITT-score, MRHFS, and EURORHFS), the AUC reached 0.98. The AUC for preoperative penKid, as a predictor of postoperative AKI, was 0.95, and after adding its predictive value to the KFR score, the AUC reached 0.97. Conclusions: In the present study, the biomarkers penKid and bio-ADM predicted clinically significant patient outcomes after LVAD implantation such as AKI, RHF, and 30-day mortality. Adding biomarkers to well-established risk scores improved the AUC for prediction of postoperative complications.