Abstract
In-hospital mortality associated with cardiogenic shock (CS) remains high despite the use of percutaneous assist devices. We sought to determine whether support with VA-ECMO or Impella in patients with CS alters specific components of the plasma proteome. Plasma samples were collected before device implantation and 72 h after initiation of support in 11 CS patients receiving ECMO or Impella. SOMAscan was used to detect 1305 circulating proteins. Sixty-seven proteins were changed after ECMO (18 upregulated and 49 downregulated, p < 0.05), 38 after Impella (10 upregulated and 28 downregulated, p < 0.05), and only eight proteins were commonly affected. Despite minimal protein overlap, both devices were associated with markers of reduced inflammation and increased apoptosis of inflammatory cells. In summary, ECMO and Impella are associated with reduced expression of inflammatory markers and increased markers of inflammatory cell death. These circulating proteins may serve as novel targets of therapy or biomarkers to tailor AMCS use.
Graphical Abstract
Patients with refractory cardiogenic shock (CS) present with increased levels of circulating proteins related to inflammation, apoptosis, and necrosis and decreased levels of circulating proteins related to angiogenesis. After 72 h of acute mechanical circulatory support (AMCS), there is reduction of circulating proteins related to inflammation, while proteins related to apoptosis and necrosis remain elevated.
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Data Availability
All data is available upon reasonable request to the corresponding author.
Abbreviations
- CS:
-
Cardiogenic shock
- ECMO:
-
Extra-corporeal membrane oxygenator
- AMCS:
-
Acute mechanical circulatory support
- IKBKB:
-
Inhibitor of nuclease factor kappa B kinase subunit beta
- NF-kB:
-
Nuclear factor kappa B
- CxCL3:
-
Chemokine (C-X-C motif) ligand 3
- STUB1:
-
STIP1 homology and U-box containing protein 1
- HSPA8:
-
Heat shock protein 8
References
Berg DD, Bohula EA, van Diepen S, Katz JN, Alviar CL, Baird-Zars VM, Barnett CF, Barsness GW, Burke JA, Cremer PC, Cruz J, Daniels LB, DeFilippis AP, Haleem A, Hollenberg SM, Horowitz JM, Keller N, Kontos MC, Lawler PR, Menon V, Metkus TS, Ng J, Orgel R, Overgaard CB, Park JG, Phreaner N, Roswell RO, Schulman SP, Jeffrey Snell R, Solomon MA, Ternus B, Tymchak W, Vikram F, Morrow DA. Epidemiology of shock in contemporary cardiac intensive care units. Circ Cardiovasc Qual Outcomes. 2019;12:e005618. https://doi.org/10.1161/circoutcomes.119.005618.
Jentzer JC, Rayfield C, Soussi S, Berg DD, Kennedy JN, Sinha SS, Baran DA, Brant E, Mebazaa A, Billia F, Kapur NK, Henry TD, Lawler PR. Advances in the staging and phenotyping of cardiogenic shock: part 1 of 2. JACC: Advances. 2022;1:100120. https://doi.org/10.1016/j.jacadv.2022.100120.
Schrage B, Ibrahim K, Loehn T, Werner N, Sinning JM, Pappalardo F, Pieri M, Skurk C, Lauten A, Landmesser U, Westenfeld R, Horn P, Pauschinger M, Eckner D, Twerenbold R, Nordbeck P, Salinger T, Abel P, Empen K, Busch MC, Felix SB, Sieweke JT, Møller JE, Pareek N, Hill J, MacCarthy P, Bergmann MW, Henriques JPS, Möbius-Winkler S, Schulze PC, Ouarrak T, Zeymer U, Schneider S, Blankenberg S, Thiele H, Schäfer A, Westermann D. Impella support for acute myocardial infarction complicated by cardiogenic shock. Circulation. 2019;139:1249–58. https://doi.org/10.1161/circulationaha.118.036614.
Zweck E, Thayer KL, Helgestad OKL, Kanwar M, Ayouty M, Garan AR, Hernandez-Montfort J, Mahr C, Wencker D, Sinha SS, Vorovich E, Abraham J, O’Neill W, Li S, Hickey GW, Josiassen J, Hassager C, Jensen LO, Holmvang L, Schmidt H, Ravn HB, Møller JE, Burkhoff D, Kapur NK. Phenotyping cardiogenic shock. J Am Heart Assoc. 2021;10:e020085. https://doi.org/10.1161/jaha.120.020085.
Candia J, Cheung F, Kotliarov Y, Fantoni G, Sellers B, Griesman T, Huang J, Stuccio S, Zingone A, Ryan BM, Tsang JS, Biancotto A. Assessment of variability in the SOMAscan assay. Sci Rep. 2017;7:14248. https://doi.org/10.1038/s41598-017-14755-5.
Epelman S, Liu PP, Mann DL. Role of innate and adaptive immune mechanisms in cardiac injury and repair. Nat Rev Immunol. 2015;15:117–29. https://doi.org/10.1038/nri3800.
Caruso R, Botta L, Verde A, Milazzo F, Vecchi I, Trivella MG, Martinelli L, Paino R, Frigerio M, Parodi O. Relationship between pre-implant interleukin-6 levels, inflammatory response, and early outcome in patients supported by left ventricular assist device: a prospective study. PLoS ONE. 2014;9:e90802. https://doi.org/10.1371/journal.pone.0090802.
Diakos NA, Thayer K, Swain L, Goud M, Jain P, Kapur NK. Systemic inflammatory burden correlates with severity and predicts outcomes in patients with cardiogenic shock supported by a percutaneous mechanical assist device. J Cardiovasc Transl Res. 2021;14:476–83. https://doi.org/10.1007/s12265-020-10078-5.
Cuinet J, Garbagnati A, Rusca M, Yerly P, Schneider AG, Kirsch M, Liaudet L. Cardiogenic shock elicits acute inflammation, delayed eosinophilia, and depletion of immune cells in most severe cases. Sci Rep. 2020;10:7639. https://doi.org/10.1038/s41598-020-64702-0.
Khachigian LM. Early growth response-1 in cardiovascular pathobiology. Circ Res. 2006;98:186–91. https://doi.org/10.1161/01.RES.0000200177.53882.c3.
Khachigian LM. Early growth response-1, an Integrative sensor in cardiovascular and inflammatory disease. J Am Heart Assoc. 2021;10:e023539. https://doi.org/10.1161/jaha.121.023539.
Wang NP, Pang XF, Zhang LH, Tootle S, Harmouche S, Zhao ZQ. Attenuation of inflammatory response and reduction in infarct size by postconditioning are associated with downregulation of early growth response 1 during reperfusion in rat heart. Shock. 2014;41:346–54. https://doi.org/10.1097/shk.0000000000000112.
Laggner M, Oberndorfer F, Golabi B, Bauer J, Zuckermann A, Hacker P, Lang I, Skoro-Sajer N, Gerges C, Taghavi S, Jaksch P, Mildner M, Ankersmit HJ, Moser B. EGR1 is implicated in right ventricular cardiac remodeling associated with pulmonary hypertension. Biology (Basel). 2022;11(5):677. https://doi.org/10.3390/biology11050677.
Roman-Blas JA, Jimenez SA. NF-kappaB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthritis Cartilage. 2006;14:839–48. https://doi.org/10.1016/j.joca.2006.04.008.
Maier HJ, Schips TG, Wietelmann A, Krüger M, Brunner C, Sauter M, Klingel K, Böttger T, Braun T, Wirth T. Cardiomyocyte-specific IκB kinase (IKK)/NF-κB activation induces reversible inflammatory cardiomyopathy and heart failure. Proc Natl Acad Sci U S A. 2012;109:11794–9. https://doi.org/10.1073/pnas.1116584109.
Thair SA, Walley KR, Nakada TA, McConechy MK, Boyd JH, Wellman H, Russell JA. A single nucleotide polymorphism in NF-κB inducing kinase is associated with mortality in septic shock. J Immunol. 2011;186:2321–8. https://doi.org/10.4049/jimmunol.1002864.
Diakos NA, Taleb I, Kyriakopoulos CP, Shah KS, Javan H, Richins TJ, Yin MY, Yen CG, Dranow E, Bonios MJ, Alharethi R, Koliopoulou AG, Taleb M, Fang JC, Selzman CH, Stellos K, Drakos SG. Circulating and myocardial cytokines predict cardiac structural and functional improvement in patients with heart failure undergoing mechanical circulatory support. J Am Heart Assoc. 2021;10:e020238. https://doi.org/10.1161/jaha.120.020238.
Noels H, Weber C, Koenen RR. Chemokines as therapeutic targets in cardiovascular disease. Arterioscler Thromb Vasc Biol. 2019;39:583–92. https://doi.org/10.1161/atvbaha.118.312037.
Bednash JS, Mallampalli RK. Regulation of inflammasomes by ubiquitination. Cell Mol Immunol. 2016;13:722–8. https://doi.org/10.1038/cmi.2016.15.
Funding
This work was supported by a grant from the National Institutes of Health (R01HL139785-01 and R01HL133215-01) to N.K.K and by the Beals Goodfellow Research Award, Boston, MA, USA to N.A.D
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration on 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
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Dr Navin Kapur has received consultant/speaker honoraria and institutional research grants from Abbott, Abiomed, Boston Scientific, Getinge, LivaNova, Medtronic, MD Start, and preCARDIA.
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Diakos, N.A., Swain, L., Bhave, S. et al. Circulating Proteome Analysis Identifies Reduced Inflammation After Initiation of Hemodynamic Support with Either Veno-Arterial Extracorporeal Membrane Oxygenation or Impella in Patients with Cardiogenic Shock. J. of Cardiovasc. Trans. Res. (2024). https://doi.org/10.1007/s12265-024-10501-1
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DOI: https://doi.org/10.1007/s12265-024-10501-1