ShockOmics: multiscale approach to the identification of molecular biomarkers in acute heart failure induced by shock

Federico Aletti, Costanza Conti, Manuela Ferrario, Vicent Ribas, Bernardo Bollen Pinto, Antoine Herpain, Emiel Post, Eduardo Romay Medina, Cristina Barlassina, Eliandre de Oliveira, Roberta Pastorelli, Gabriella Tedeschi, Giuseppe Ristagno, Fabio S Taccone, Geert W Schmid-Schönbein, Ricard Ferrer, Daniel De Backer, Karim Bendjelid, Giuseppe Baselli, Federico Aletti, Costanza Conti, Manuela Ferrario, Vicent Ribas, Bernardo Bollen Pinto, Antoine Herpain, Emiel Post, Eduardo Romay Medina, Cristina Barlassina, Eliandre de Oliveira, Roberta Pastorelli, Gabriella Tedeschi, Giuseppe Ristagno, Fabio S Taccone, Geert W Schmid-Schönbein, Ricard Ferrer, Daniel De Backer, Karim Bendjelid, Giuseppe Baselli

Abstract

Background: The ShockOmics study (ClinicalTrials.gov identifier NCT02141607) is a multicenter prospective observational trial aimed at identifying new biomarkers of acute heart failure in circulatory shock, by means of a multiscale analysis of blood samples and hemodynamic data from subjects with circulatory shock.

Methods and design: Ninety septic shock and cardiogenic shock patients will be recruited in three intensive care units (ICU) (Hôpital Erasme, Université Libre de Bruxelles, Belgium; Hospital Universitari Mutua Terrassa, Spain; Hôpitaux Universitaires de Genève, Switzerland). Hemodynamic signals will be recorded every day for up to seven days from shock diagnosis (time T0). Clinical data and blood samples will be collected for analysis at: i) T1 < 16 h from T0; ii) T2 = 48 h after T0; iii) T3 = day 7 or before discharge or before discontinuation of therapy in case of fatal outcome; iv) T4 = day 100. The inclusion criteria are: shock, Sequential Organ Failure Assessment (SOFA) score > 5 and lactate levels ≥ 2 mmol/L. The exclusion criteria are: expected death within 24 h since ICU admission; > 4 units of red blood cells or >1 fresh frozen plasma transfused; active hematological malignancy; metastatic cancer; chronic immunodepression; pre-existing end stage renal disease requiring renal replacement therapy; recent cardiac surgery; Child-Pugh C cirrhosis; terminal illness. Enrollment will be preceded by the signature of the Informed Consent by the patient or his/her relatives and by the physician in charge. Three non-shock control groups will be included in the study: a) healthy blood donors (n = 5); b) septic patients (n = 10); c) acute myocardial infarction or patients with prolonged acute arrhythmia (n = 10). The hemodynamic data will be downloaded from the ICU monitors by means of dedicated software. The blood samples will be utilized for transcriptomics, proteomics and metabolomics ("-omics") analyses.

Discussion: ShockOmics will provide new insights into the pathophysiological mechanisms underlying shock as well as new biomarkers for the timely diagnosis of cardiac dysfunction in shock and quantitative indices for assisting the therapeutic management of shock patients.

Figures

Fig. 1
Fig. 1
Time course of the monitoring of a patient enrolled in the ShockOmics study (hemodynamic data acquisition and blood samples). The hemodynamic data are collected daily during the observation window (up from time 0 on day 1 up to day 7). The total number of blood samples is 3: the first sample is collected at T1, the second at T2, and the third at T3, which can occur on any day between day 4 and day 7 (T3 occurring on day 7 in case of ICU stay longer than 7 days or on day 4–6 in case of early discharge or death)

References

    1. Vincent JL, De Backer D. Circulatory shock. N Engl J Med. 2013;369(18):1726–34. doi: 10.1056/NEJMra1208943.
    1. Vincent JL, De Backer D. Circulatory shock. N Engl J Med. 2014;370(6):583.
    1. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock 2012. Crit Care Med. 2013;41:580–637. doi: 10.1097/CCM.0b013e31827e83af.
    1. Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, Romero M, et al. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014;370:1412–21. doi: 10.1056/NEJMoa1305727.
    1. Hoyert DL, Xu J. Deaths: preliminary data for 2011. Natl Vital Stat Rep. 2011;61(6):1–52.
    1. Martin GS, Maninno DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 to 2000. N Engl J Med. 2003;348:1546–54. doi: 10.1056/NEJMoa022139.
    1. Angus DC, Pereira CA, Silva E. Epidemiology of severe sepsis around the world. Endocr Metab Immune Disord Drug Targets. 2006;6:207–12. doi: 10.2174/187153006777442332.
    1. Moss M, Martin GS. A global perspective on the epidemiology of sepsis. Intensive Care Med. 2004;30:527–9. doi: 10.1007/s00134-004-2182-z.
    1. O’Brien JM, Jr, Ali NA, Aberegg SK, Abraham E. Sepsis. Am J Med. 2007;120:1012–22. doi: 10.1016/j.amjmed.2007.01.035.
    1. Investigators PCESS, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370:1683–93. doi: 10.1056/NEJMoa1401602.
    1. ARISE Investigators. ANZICS Clinical Trials Group. Peake SL, Delaney A, Bailey M, Bellomo R, et al. Goal-directed resuscitation for patients with early septic shock. N Engl J Med. 2014;371:1496–506. doi: 10.1056/NEJMoa1404380.
    1. Mouncey PR, Osborn TM, Power GS, Harrison DA, Sadique MZ, Grieve RD, et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015;372(14):1301–11. doi: 10.1056/NEJMoa1500896.
    1. Jeger RV, Radovanovic D, Hunziker PR, Pfisterer ME, Stauffer JC, Erne P, et al. Ten-year trends in the incidence and treatment of cardiogenic shock. Ann Intern Med. 2008;149:618–26. doi: 10.7326/0003-4819-149-9-200811040-00005.
    1. Reynolds HR, Hochman JS. Cardiogenic shock: current concepts and improving outcomes. Circulation. 2008;117:686–97. doi: 10.1161/CIRCULATIONAHA.106.613596.
    1. Thiele H, Zeymer U, Neumann FJ, Ferenc M, Olbrich HG, Hausleiter J, et al. Intraaortic balloon support for myocardial infarction with cardiogenic shock. N Engl J Med. 2012;367:1287–96. doi: 10.1056/NEJMoa1208410.
    1. Shackford SR, Mackersie RC, Holbrook TL, Davis JW, Hollingsworth- Fridlund P, Hoyt DB, et al. The epidemiology of traumatic death. A population-based analysis. Arch Surg. 1993;128:571–5. doi: 10.1001/archsurg.1993.01420170107016.
    1. Sauaia A, Moore FA, Moore EE, Moser KS, Brennan R, Read RA, et al. Epidemiology of trauma deaths: a reassessment. J Trauma. 1995;38:185–93. doi: 10.1097/00005373-199502000-00006.
    1. Rudiger A, Singer M. Mechanisms of sepsis-induced cardiac dysfunction. Crit Care Med. 2007;35:1599–608. doi: 10.1097/01.CCM.0000266683.64081.02.
    1. Zanotti-Cavazzoni SL, Hollenberg SM. Cardiac dysfunction in severe sepsis and septic shock. Curr Opin Crit Care. 2009;15:392–7. doi: 10.1097/MCC.0b013e3283307a4e.
    1. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368–77. doi: 10.1056/NEJMoa010307.
    1. Rivers EP, Katranji M, Jaehne KA, Brown S, Dagher GA, Cannon C, et al. Early interventions in severe sepsis and septic shock: a review of the evidence one decade later. Minerva Anestesiol. 2012;78:712–24.
    1. Cecconi M, De Backer D, Antonelli M, Beale R, Bakker J, Hofer C, et al. Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med. 2014;40:1795–815. doi: 10.1007/s00134-014-3525-z.
    1. Ley K, Gaehtgens P. Microcirculation disorders in shock. Klin Anasthesiol Intensivther. 1987;33:19–36. doi: 10.1007/978-3-642-72533-3_2.
    1. Hinshaw LB. Sepsis/septic shock: participation of the microcirculation: an abbreviated review. Crit Care Med. 1996;24:1072–8. doi: 10.1097/00003246-199606000-00031.
    1. Yao YM, Redl H, Bahrami S, Schlag G. The inflammatory basis of trauma/shock-associated multiple or6an failure. Inflamm Res. 1998;47:201–10. doi: 10.1007/s000110050318.
    1. Schmid-Schönbein GW. Inflammation and the autodigestion hypothesis. Microcirculation. 2009;16:289–306. doi: 10.1080/10739680902801949.
    1. DeLano FA, Hoyt DB, Schmid-Schönbein GW. Pancreatic digestive enzyme blockade in the intestine increases survival after experimental shock. Sci Transl Med. 2013;5(169):169ra11. doi: 10.1126/scitranslmed.3005046.
    1. Fruchterman TM, Spain DA, Wilson MA, Harris PD, Garrison RN. Selective microvascular endothelial cell dysfunction in the small intestine following resuscitated hemorrhagic shock. Shock. 1998;10:417–22. doi: 10.1097/00024382-199812000-00007.
    1. Jarrar D, Wang P, Cioffi WG, Bland KI, Chaudry IH. Critical role of oxygen radicals in the initiation of heatic depression after trauma hemorrhage. J Trauma. 2000;49:879–85. doi: 10.1097/00005373-200011000-00015.
    1. Kaiser VL, Sifri ZC, Senthil M, Dikdan GS, Lu Q, Xu DZ, et al. Albumin peptide: a molecular marker for trauma/hemorrhagic-shock in rat mesenteric lymph. Peptides. 2005;26:2491–9. doi: 10.1016/j.peptides.2005.05.001.
    1. Kien ND, Antognini JF, Reilly DA, Moore PG. Small-volume resuscitation using hypertonic saline improves organ perfusion in burned rats. Anesth Analg. 1996;83:782–8.
    1. Singer M. Catecholamine treatment for shock--equally good or bad? Lancet. 2007;370:636–7. doi: 10.1016/S0140-6736(07)61317-8.
    1. Morelli A, Ertmer C, Westphal M, Rehberg S, Kampmeier T, Ligges S, et al. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA. 2013;310:1683–91. doi: 10.1001/jama.2013.278477.
    1. De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010;362:779–89. doi: 10.1056/NEJMoa0907118.
    1. Deitch EA. Gut lymph and lymphatics: a source of factors leading to organ injury and dysfunction. Ann N Y Acad Sci. 2010;1207:E103–11. doi: 10.1111/j.1749-6632.2010.05713.x.
    1. Minne L, Abu-Hanna A, de Jonge E. Evaluation of SOFA-based models for predicting mortality in the ICU: a systematic review. Crit Care. 2008;12(6):R161. doi: 10.1186/cc7160.
    1. Cowie MR, Wood DA, Coats AJ, Thompson SG, Poole-Wilson PA, Suresh V, et al. Incidence and aetiology of heart failure; a population-based study. Eur Heart J. 1999;20:421–8. doi: 10.1053/euhj.1998.1280.
    1. Zannad F, Mebazaa A, Juillière Y, Cohen-Solal A, Guize L, Alla F, et al. Clinical profile, contemporary management and one-year mortality in patients with severe acute heart failure syndromes: the EFICA study. Eur J Heart Fail. 2006;8:697–705. doi: 10.1016/j.ejheart.2006.01.001.
    1. Alla F, Zannad F, Filippatos G. Epidemiology of acute heart failure syndromes. Heart Fail Rev. 2007;12:91–5. doi: 10.1007/s10741-007-9009-2.

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