Circulating Monocyte Chemoattractant Protein-1 in Patients with Cardiogenic Shock Complicating Acute Myocardial Infarction Treated with Mild Hypothermia: A Biomarker Substudy of SHOCK-COOL Trial

Wenke Cheng, Georg Fuernau, Steffen Desch, Anne Freund, Hans-Josef Feistritzer, Janine Pöss, Petra Buettner, Holger Thiele, Wenke Cheng, Georg Fuernau, Steffen Desch, Anne Freund, Hans-Josef Feistritzer, Janine Pöss, Petra Buettner, Holger Thiele

Abstract

Background: There is evidence that monocyte chemoattractant protein-1 (MCP-1) levels reflect the intensity of the inflammatory response in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI) and have a predictive value for clinical outcomes. However, little is known about the effect of mild therapeutic hypothermia (MTH) on the inflammatory response in patients with CS complicating AMI. Therefore, we conducted a biomarker study to investigate the effect of MTH on MCP-1 levels in patients with CS complicating AMI.

Methods: In the randomized mild hypothermia in cardiogenic shock (SHOCK-COOL) trial, 40 patients with CS complicating AMI were enrolled and assigned to MTH (33 °C) for 24 h or normothermia at a 1:1 ratio. Blood samples were collected at predefined time points at the day of admission/day 1, day 2 and day 3. Differences in MCP-1 levels between and within the MTH and normothermia groups were assessed. Additionally, the association of MCP-1 levels with the risk of all-cause mortality at 30 days was analyzed. Missing data were accounted for by multiple imputation as sensitivity analyses.

Results: There were differences in MCP-1 levels over time between patients in MTH and normothermia groups (P for interaction = 0.013). MCP-1 levels on day 3 were higher than on day 1 in the MTH group (day 1 vs day 3: 21.2 [interquartile range, 0.25-79.9] vs. 125.7 [interquartile range, 87.3-165.4] pg/mL; p = 0.006) and higher than in the normothermia group at day 3 (MTH 125.7 [interquartile range, 87.3-165.4] vs. normothermia 12.3 [interquartile range, 0-63.9] pg/mL; p = 0.011). Irrespective of therapy, patients with higher levels of MCP-1 at hospitalization tended to have a decreased risk of all-cause mortality at 30 days (HR, 2.61; 95% CI 0.997-6.83; p = 0.051).

Conclusions: The cooling phase of MTH had no significant effect on MCP-1 levels in patients with CS complicating AMI compared to normothermic control, whereas MCP-1 levels significantly increased after rewarming.

Trial registration: NCT01890317.

Keywords: acute myocardial infarction; cardiogenic shock; mild therapeutic hypothermia; monocyte chemoattractant protein-1.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Study flow. SHOCK-COOL, the randomized trial of mild hypothermia for cardiogenic shock. MTH, mild therapeutic hypothermia.
Figure 2
Figure 2
MCP-1 levels of patients in cardiogenic shock after acute myocardial infarction treated by either mild therapeutic hypothermia (MTH) or normothermia 1, 2 and 3 days following hospitalization. Box and whisker plots show median and interquartile range.
Figure 3
Figure 3
Kaplan–Meier analysis for time to death within the first 30 days in cardiogenic shock complicating acute myocardial infarction patients with MCP-1 levels median (black dashed line) on day 1.

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