Abstract
BackgroundLeft 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).MethodsWe 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.ResultsMedian 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).ConclusionsInitial 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.
Highlights
Left ventricular remodeling following ST-elevation myocardial infarction (STEMI) is associated with poor outcome, including heart failure (HF)
The present study is the first to show that after admission for STEMI highest levels of plasma neprilysin are associated with lower left ventricular ejection fraction (LVEF) and a trend towards lower End-diastolic volume (EDV) at baseline, and higher magnitude of improvement of LVEF at follow-up when compared to other groups
These findings suggest that high neprilysin levels may
Summary
Left ventricular remodeling following ST-elevation myocardial infarction (STEMI) is associated with poor outcome, including heart failure (HF). LVR is the consequence of cellular and histological modifications, such as myocyte hypertrophy, apoptosis and extracellular matrix remodeling [4] These phenomena are induced by deleterious adaptive mechanical and neurohormonal responses, including the renin-angiotensin-aldosterone system (RAAS) [5]. Angiotensin-converting enzyme (ACE) inhibition following STEMI associated with a significant reduction in mortality [6] and decreased LVR through suppression of the activity of the RAAS [7] is to be considered in all STEMI patients [8]. The aim of the present study was to assess the association between serum levels of neprilysin and LV volumes, function and remodeling in STEMI patients at baseline and 6 ± 1 month follow-up
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