Plasma Lactate Dehydrogenase Levels Predict Mortality in Acute Aortic Syndromes: A Diagnostic Accuracy and Observational Outcome Study

Abstract

In acute aortic syndromes (AAS), organ malperfusion represents a key event impacting both on diagnosis and outcome. Increased levels of plasma lactate dehydrogenase (LDH), a biomarker of malperfusion, have been reported in AAS, but the performance of LDH for the diagnosis of AAS and the relation of LDH with outcome in AAS have not been evaluated so far.This was a bi-centric prospective diagnostic accuracy study and a cohort outcome study. From 2008 to 2014, patients from 2 Emergency Departments suspected of having AAS underwent LDH assay at presentation. A final diagnosis was obtained by aortic imaging. Patients diagnosed with AAS were followed-up for in-hospital mortality.One thousand five hundred seventy-eight consecutive patients were clinically eligible, and 999 patients were included in the study. The final diagnosis was AAS in 201 (20.1%) patients. Median LDH was 424 U/L (interquartile range [IQR] 367-557) in patients with AAS and 383 U/L (IQR 331-460) in patients with alternative diagnoses (P < 0.001). Using a cutoff of 450 U/L, the sensitivity of LDH for AAS was 44% (95% confidence interval [CI] 37-51) and the specificity was 73% (95% CI 69-76). Overall in-hospital mortality for AAS was 23.8%. Mortality was 32.6% in patients with LDH ≥ 450 U/L and 16.8% in patients with LDH < 450 U/L (P = 0.006). Following stratification according to LDH quartiles, in-hospital mortality was 12% in the first (lowest) quartile, 18.4% in the second quartile, 23.5% in the third quartile, and 38% in the fourth (highest) quartile (P = 0.01). LDH ≥ 450 U/L was further identified as an independent predictor of death in AAS both in univariate and in stepwise logistic regression analyses (odds ratio 2.28, 95% CI 1.11-4.66; P = 0.025), in addition to well-established risk markers such as advanced age and hypotension. Subgroup analysis showed excess mortality in association with LDH ≥ 450 U/L in elderly, hemodynamically stable and in nonsurgically treated patients.Plasma LDH constitutes a biomarker of poor outcome in patients with AAS. LDH is a rapid and universally available assay that could be used to improve risk stratification and to individualize treatment in patient groups where options are controversial.

FIGURE 1

Flow diagram of the study. AAS = acute aortic syndrome, AltD = alternative diagnosis, CTA = computed tomography angiography.

FIGURE 2

Plasma LDH distribution and diagnostic performance in study patients. (A) Box-whisker graph of LDH in patients with final diagnosis of acute aortic syndrome (AAS) or alternative diagnosis (AltD). (B) Box-whisker graph of LDH in patients with final diagnosis of Stanford type A aortic dissection (Stanf. A) or other forms of AAS (Stanford type B aortic dissection, intramural hematoma, and penetrating aortic ulcer). For A and B, central lines represent median value, boxes represent interquartile range, and whiskers the 10th to 90th percentile range. Group comparison was performed with Mann–Whitney nonparametric U test. Data are presented in a log₂ scale. (C) Receiver operated characteristic curve of LDH for the diagnosis of AAS. (D) Plots of sensitivity (continuous line) and specificity (dashed line) of LDH for the diagnosis of AAS using different cutoffs. LDH = lactate dehydrogenase.

FIGURE 3

In-hospital mortality of study patients (n = 193) with acute aortic syndrome stratified according to plasma LDH at presentation to the Emergency Department. (A) Kaplan–Meier survival curves of patients stratified according to the higher normality cutoff of LDH (450 U/L). (B) Kaplan–Meier survival curves of patients stratified according to quartiles of LDH: Q1 (LDH < 367 U/L), Q2 (LDH 367–424 U/L), Q3 (LDH 425–557 U/L), Q4 (LDH > 557 U/L). LDH = lactate dehydrogenase.

FIGURE 4

Association of plasma LDH levels (cutoff 450 U/L) with in-hospital mortality in patient subgroups. <70y = age < 70 y, ≥70 y = age ≥ 70 y, AAS = acute aortic syndrome, LDH = lactate dehydrogenase, medical = nonsurgical treatment, Other = other types of AAS (Stanford type B aortic dissection, intramural hematoma, and penetrating aortic ulcer), StA = Stanford type A aortic dissection, stable = hemodynamically stable, surgical = surgical treatment, unstable = hemodynamically unstable.