Plasma levels of mitochondrial and nuclear DNA in patients with massive pulmonary embolism in the emergency department: a prospective cohort studyReport as inadecuate

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Critical Care

, 17:R90

First Online: 24 May 2013Received: 21 December 2012Revised: 16 March 2013Accepted: 24 May 2013


IntroductionCell-free plasma mitochondrial DNA mt-DNA and nuclear DNA n-DNA are biomarkers with prognostic utility in conditions associated with a high rate of cell death. This exploratory study aimed to determine the plasma levels of both nucleic acids in patients with massive and submassive pulmonary embolism PE and to compare them with other biomarkers, such as heart-type fatty acid-binding protein H-FABP and troponin I Tn-I

MethodsThis was a prospective observational study of 37 consecutive patients with massive PE, 37 patients with submassive PE, and 37 healthy subjects. Quantifications of plasma mt-DNA and n-DNA with real-time quantitative polymerase chain reaction PCR, and plasma H-FABP and Tn-I by commercial assays, were done on blood samples drawn within 4 hours after presentation at the emergency department.

ResultsPlasma mt-DNA and n-DNA concentrations were much higher in patients with massive PE median, 2,970 GE-ml; interquartile range IQR, 1,050 to 5,485; and 3,325 GE-ml, IQR: 1,080 to 5,790, respectively than in patients with submassive PE 870 GE-ml and 1,245 GE-ml, respectively; P < 0.01 or controls 185 GE-ml and 520 GE-ml, respectively. Eighteen patients with massive PE died of a PE-related cause by day 15 of observation. Plasma mt-DNA and n-DNA values were 2.3-fold and 1.9-fold higher in the subgroup of nonsurviving patients than in survivors. H-FABP and Tn-I values were also higher in patients with massive PE who died 7.3 ng-ml and 0.023 ng-ml, respectively than in those who survived 6.4 ng-ml, and 0.016 ng-ml, respectively. By receiver operating curve ROC analysis, the best cutoff values for predicting 15-day mortality were 3,380 GE-ml for mt-DNA, 6.8 ng-ml for H-FABP, 3,625 GE-ml for n-DNA, and 0.020 ng-ml for Tn-I, based on the calculated areas under the curve AUCs of 0.89 95% confidence interval CI, 0.78 to 0.99, 0.76 95% CI, 0.69 to 093, 0.73 95% CI, 0.58 to 0.91, and 0.59 95% CI, 0.41 to 0.79, respectively. By stepwise logistic regression, a plasma mt-DNA concentration greater than 3,380 GE-ml adjusted odds ratio OR, 8.22; 95% CI, 1.72 to 39.18; P < 0.001 and a plasma value of H-FBAP >6.8 ng-ml OR, 5.36; 95% CI, 1.06 to 27.08; P < 0.01 were the only independent predictors of mortality.

Conclusionsmt-DNA and H-FBAP might be promising markers for predicting 15-day mortality in massive PE, with mt-DNA having better prognostic accuracy.

Keywordsplasma mitochondrial DNA plasma nuclear DNA cell-free plasma DNA heart-type fatty acid-binding protein hospital mortality massive pulmonary embolism prognosis AbbreviationsAUCarea under the curve

BNPbrain natriuretic peptide

H-FBAPheart-type fatty acid-binding protein

mt-DNAmitochondrial DNA

n-DNAnuclear DNA

ROCreceiver operating curve

RVright ventricle. sFas: soluble form of Fas molecule

sFasLsoluble form of Fas ligand molecule

Tn-Itroponin I.

Electronic supplementary materialThe online version of this article doi:10.1186-cc12735 contains supplementary material, which is available to authorized users.

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Author: Francisco Arnalich - Maria Constanza Maldifassi - Enrique Ciria - Rosa Codoceo - Jaime Renart - Carmen Fernández-Capitán


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