Serum neprilysin levels are associated with myocardial stunning after ST-elevation myocardial infarction

Abstract

Background Left ventricular remodeling following ST-elevation myocardial infarction (STEMI) is associated with poor outcome, including heart failure (HF). Neprilysin inhibition leads to improved outcome in patients with altered left ventricular ejection fraction (LVEF). Methods We aimed to assess the association between serum levels of neprilysin and left ventricular (LV) volumes, function and remodeling in STEMI patients with successful myocardial reperfusion and no clinical sign of HF. Sixty-eight patients were admitted for STEMI and had both plasma neprilysin measurement at baseline and 3D transthoracic echocardiogram at baseline and after a median follow-up of 7 months. We compared 3 groups: a group with a low-level of plasma neprilysin (< 125 pg/mL, i.e. the lower limit of detection of the assay) and the two other groups were defined as being below or above the median value of the remaining samples. Results Median age was 58.5 ± 12.8 years and 56 (82.4%) were men. Median LVEF was 45.0 ± 8.5%. Baseline characteristics were comparable between groups (low-level of neprilysin group [≤125 pg/mL, n = 38], medium-level of neprilysin group [126–450 pg/mL, n = 15] and a high-level group [> 450 pg/mL, n = 15]). At baseline there was a non-significant trend towards lower end-diastolic volume (p = 0.07) but significantly lower LVEF in the high neprilysin group (46.4 ± 8.3%, 47.1 ± 8.1% and 39.1 ± 6.9%, p < 0.01). At follow-up, the magnitude of LVEF increase was significantly more important in the high neprilysin group compared to the other groups (p = 0.022 for relative change in LVEF and 6.6 ± 7.3%, 3.6 ± 9.0% and 11.3 ± 8.4%, p = 0.031 for absolute change in LVEF) resulting in similar LVEF levels at follow-up between all groups (53.0 ± 8.9%, 50.6 ± 9.7% and 50.4 ± 9.9%, p = 0.55). Conclusions Initial high neprilysin levels may identify patients with stunned myocardium early after STEMI, with a recovery of contractility leading to improved LVEF at follow-up. Future studies will have to assess the role of neprilysin in the setting of STEMI and the potential benefit of its blockade.

Emerging Biomarkers for Predicting Clinical Outcomes in Patients with Heart Disease

“…Patients with higher levels of nardilysin ( n -arginine dibasic convertase, a type of metalloendopeptidase) at admission for STEMI were shown to be at increased risk for future all-cause mortality [ 103 ]. Higher neprilysin (also known as CD10 or common acute lymphoblastic leukemia antigen—CALLA) levels were associated with stunned myocardium early after STEMI, with better improvement of LVEF at follow-up [ 104 ]. Serum matrix metalloproteinase 9 (MMP-9) is a candidate biomarker for the early discrimination of MI from unstable angina and a predictor of poor clinical outcomes in patients with ACS [ 105 ].…”

Is plasma concentration of coenzyme Q10 a predictive marker for left ventricular remodelling after revascularization for ST-segment elevation myocardial infarction?

“…with inclusion and exclusion criteria previously described. 21 The study complied with the Declaration of Helsinki and was approved by the local ethics committee (protocol number A14-D17-VOL.20).…”

“…and obtained by experienced ultrasonographers who were blinded to the patients’ plasma CoQ10 concentrations. 21 Left ventricular volumes and ejection fraction were measured using 3D echocardiography as recommended. 25 Adverse LVR was defined as a 20% increase in end-diastolic volume between baseline and follow-up imaging sessions.…”