miRNA-200b-A Potential Biomarker Identified in a Porcine Model of Cardiogenic Shock and Mechanical Unloading.

Background: Cardiogenic shock (CS) alters whole body metabolism and circulating biomarkers serve as prognostic markers in CS patients. Percutaneous ventricular assist devices (pVADs) unload the left ventricle by actively ejecting blood into the aorta. The goal of the present study was to identify alterations in circulating metabolites and transcripts in a large animal model that might serve as potential prognostic biomarkers in acute CS and additional left ventricular unloading by Impella ® pVAD support. Methods: CS was induced in a preclinical large animal model by injecting microspheres into the left coronary artery system in six pigs. After the induction of CS, mechanical pVAD support was implemented for 30 min total. Serum samples were collected under basal conditions, after the onset of CS, and following additional pVAD unloading. Circulating metabolites were determined by metabolomic analysis, circulating RNA entities by RNA sequencing. Results: CS and additional pVAD support alter the abundance of circulating metabolites involved in Aminoacyl-tRNA biosynthesis and amino acid metabolism. RNA sequencing revealed decreased abundance of the hypoxia sensitive miRNA-200b following the induction of CS, which was reversed following pVAD support. Conclusion: The hypoxamir miRNA-200b is a potential circulating marker that is repressed in CS and is restored following pVAD support. The early transcriptional response with increased miRNA-200b expression following only 30 min of pVAD support suggests that mechanical unloading alters whole body metabolism. Future studies are required to delineate the impact of serum miRNA-200b levels as a prognostic marker in patients with acute CS and pVAD unloading.

Association of Body Mass Index with Mortality in Patients with Cardiogenic Shock following Acute Myocardial Infarction: A Contemporary Danish Cohort Analysis.

AIMS: The obesity paradox suggests a better prognosis in overweight or obese patients with heart failure and acute myocardial infarction (AMI) than patients with normal weight. Few studies have investigated the association between BMI and mortality in patients with AMI complicated by cardiogenic shock (AMICS). The aim of this study was to evaluate the association between BMI and 30-day mortality in patients with AMICS. METHODS AND RESULTS: A retrospective study of 1,716 patients with AMICS treated at 2 tertiary centers in south-eastern Denmark between 2010 and 2017. Patients undergoing revascularization and who were admitted to the intensive care unit were included (n = 1,216). BMI was available in 1,017 patients (83.6%). Patients were divided according to the WHO classification as normal weight BMI <24.9 kg/m2 (n = 453), overweight BMI 25-29.9 kg/m2 (n = 391), obese class 1 BMI 30-34.9 kg/m2 (n = 131), and obese class 2 + 3 BMI >35 kg/m2 (n = 42). Differences in baseline characteristics, in-hospital treatment, and the primary outcome of all-cause mortality at 30 days were examined. Obese patients had more comorbidities such as diabetes, hypertension, and dyslipidemia than patients with normal weight. Need for renal replacement therapy was higher among obese patients (normal weight, 19% vs. obese class 2 + 3, 35%, p = 0.02); otherwise, no difference in management was found. No difference in 30-day mortality was observed between groups (normal weight 44%, overweight 38%, obese class 1 41%, and obese class 2 + 3 45% at 30 days; ns). CONCLUSIONS: Thirty-day mortality in patients with AMICS was not associated with the BMI category. Thus, evidence of an "obesity paradox" was not observed in this contemporary cohort of patients with AMICS in Denmark.

Influence of Timing and Predicted Risk on Mortality in Impella-Treated Infarct-Related Cardiogenic Shock Patients.

Background: In-hospital mortality in acute myocardial infarction-related cardiogenic shock (AMI-CS) remains high. The only adequately powered randomized trial showed no benefit of routine use of the intra-aortic balloon pump in AMI-CS. We compared individually predicted mortality using CardShock- and IABP-Shock II-scores in AMI-CS patients treated with an Impella microaxial pump, who met the IABP-Shock II-trials inclusion/exclusion criteria, to observed mortality on circulatory support in order to determine whether standardized use of an Impella microaxial flow-pump in AMI-CS is associated with lower than predicted mortality rates and whether timing of implantation or selecting patients based on predicted risk is meaningful. Methods and Results: We analyzed data from 166 consecutive Impella-treated AMI-CS patients meeting the inclusion/exclusion criteria of the IABP-Shock II-trial (age 64 ± 11 years). Thirty-nine percentage of 64 patients had been resuscitated before Impella implantation. Overall 30-day mortality was 42%. Mortality was higher in resuscitated patients (50 vs. 36%, p = 0.0452) and when Impella was implanted post-PCI (Impella-pre-PCI: 28%, Impella-post-PCI: 51%, p = 0.0039). While in both score systems there was no significant difference between predicted and observed overall 30-day mortality, predicted mortality was significantly higher than observed mortality on Impella support only for individuals with highest predicted risk based on CardShock score (predicted 77 vs. observed 51%, p = 0.025). Conclusions: Our retrospective analysis suggests that the use of the Impella microaxial pump may be effective in selected cases of high risk patients with AMI-CS. Condensed abstract: Mortality is high in acute myocardial infarction-related cardiogenic shock despite rapid revascularization. Haemodynamic support with an intraortic balloon pump does not reduce mortality. In this retrospective registry including 166 consecutive IABP-Shock II-eligible cardiogenic shock patients in four dedicated shock centers, observed mortality on circulatory support with an Impella was significantly lower than predicted in patients with highest mortality risk. Implantation prior to PCI in acute myocardial infarction-related cardiogenic shock seemed to be associated with lower mortality than implantation post PCI.