Etiology of Myocardial Injury in Critically Ill Patients with Sepsis: A Cohort Study.

RATIONALE Myocardial injury occurs frequently during sepsis and is independently associated with mortality. However, its etiology remains largely unknown. OBJECTIVE Our aim was to assess the relative contributions of hyperinflammation, activated coagulation, and endothelial dysfunction to myocardial injury in critically ill patients with sepsis. METHODS We included consecutive patients with sepsis presenting to two tertiary intensive care units in the Netherlands between 2011 and 2013. High-sensitivity cardiac troponin I (hscTnI), as well as a wide range of plasma biomarkers related to inflammation, coagulation, and endothelial function were measured. Structural equation modeling (SEM) was used to construct latent variables representing each of these pathophysiological constructs, and to subsequently study their associations with troponin elevation while adjusting for confounders. RESULTS We analyzed 908 (88%) of 1037 eligible patients, 553 (61%) of whom had raised hs-cTnI levels upon intensive care unit admission. The latent variables included interleukin (IL)-6, IL-8 and IL-1β for inflammation; platelet count, prothrombin time and protein C for coagulation; and sE-selectin, intercellular adhesion molecule-1 and angiopoietin-2 for endothelial function. After adjustment for age and cardiovascular comorbidities, SEM analysis showed that activated coagulation was independently associated with elevated troponin during sepsis (standardized regression coefficient 0.551, 95% CI 0.257-0.845, p-value <0.001), whereas hyperinflammation and endothelial dysfunction were not (standardized regression coefficients -0.161, 95% CI -0.418-0.096, and -0.054, 95% CI -0.168-0.060, respectively). CONCLUSIONS Our findings suggest that myocardial injury during sepsis is mediated by systemic activation of coagulation, rather than by circulating inflammatory mediators or by activation of the endothelium. These findings may guide evaluation of strategies to protect the myocardium during sepsis. Clinical trial registered with clinicaltrials.gov (NCT01905033).