Release of mitochondrial DNA is associated with mortality in severe acute heart failure.

Abstract

Inflammation is regarded as an important trigger for disease progression in heart failure. Particularly in severe acute heart failure, tissue hypoxia may lead to cellular damage and the release of intracellular mitochondrial DNA, which acts as an activator of the immune system due to its resemblance to bacterial DNA. It may therefore serve as a mediator of disease progression. The aim of this study was to determine circulating levels of mitochondrial DNA and its association with mortality in patients with heart failure in different presentations. Plasma levels of circulating mitochondrial DNA were measured in 90 consecutive patients with severe acute heart failure admitted to our medical intensive care unit as well as 109 consecutive chronic heart failure patients. In patients admitted to our medical intensive care unit (median age 64 (49-74) years, median NT-pro-brain natriuretic peptide 4986 (1525-23,842) pg/mL, 30-day survival 64.4%), mitochondrial DNA levels were significantly higher in patients who died within 30 days after intensive care unit admission, and patients with plasma levels of mitochondrial DNA in the highest quartile had a 3.4-fold increased risk (P=0.002) of dying independent of renal function, vasopressor use and NT-pro-brain natriuretic peptide, troponin T, lactate levels or CardShock and acute physiology and chronic health evaluation II score. However, mitochondrial DNA did not provide incremental prognostic accuracy on top of the current gold standard acute physiology and chronic health evaluation II. Patients with severe acute heart failure showed significantly higher mitochondrial DNA levels (P<0.005) as compared to patients with chronic heart failure. In these patients, mitochondrial DNA levels were associated with the New York Heart Association functional class but were not associated with outcome. The release of mitochondrial DNA into the circulation is associated with mortality in patients with severe acute heart failure but not in patients with chronic heart failure. The release of mitochondrial DNA may therefore play a role within the pathophysiology of acute heart failure, which warrants further research. However, the use of mitochondrial DNA as a biomarker for risk stratification in these patients is of limited utility.