Endotoxemia in Acute Heart Failure and Cardiogenic Shock: Evidence, Mechanisms and Therapeutic Options
Open accessAbstract
Acute heart failure and cardiogenic shock are frequently occurring and deadly conditions. In patients with those conditions, endotoxemia related to gut injury and gut barrier dysfunction is usually described as a driver of organ dysfunction. Because endotoxemia might reciprocally alter cardiac function, this phenomenon has been suggested as a potent vicious cycle that worsens organ perfusion and leading to adverse outcomes. Yet, evidence beyond this phenomenon might be overlooked, and mechanisms are not fully understood. Subsequently, even though therapeutics available to reduce endotoxin load, there are no indications to treat endotoxemia during acute heart failure and cardiogenic shock. In this review, we first explore the evidence regarding endotoxemia in acute heart failure and cardiogenic shock. Then, we describe the main treatments for endotoxemia in the acute setting, and we present the challenges that remain before personalized treatments against endotoxemia can be used in patients with acute heart failure and cardiogenic shock.
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Gut barrier dysfunction during septic shock can lead to impaired cardiac function via endotoxemia.
“Gut barrier dysfunction during septic shock can lead to impaired cardiac function via endotoxemia [25].”
From Gastrointestinal function and nutritional interventions in septic shock (2025) · cites this paper as [25]
The Introduction describes gut barrier failure leading to endotoxemia, which can reduce cardiac performance. But it frames this pathway around acute heart failure and cardiogenic shock, not septic shock; the discussion of gut barrier function in Section 2.2 likewise concerns acute heart failure. The septic-shock passages address endotoxin treatments rather than establishing the claimed pathway in that setting. (LLM, conf=0.88)
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“Nevertheless, the effects of selective decontamination on endotoxemia in cardiac surgical patients are controversial [61,62].”
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“Abbreviations AHF Acute heart failure CHF Chronic heart failure HDL High density lipoprotein I-FABP Intestinal fatty acid binding protein LPS Lipopolysaccharides LDL Low density lipoprotein RLT Reverse lipopolysaccharide transport RCT Randomized control trial TLR Toll-like receptor”
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“, the presence of LPS in the circulation) through gut barrier failure [2].”
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“Indeed, two RCTs that focused on plasma filtration and adsorption of cytokines in septic shock patients were interrupted prematurely due to possible harmful effects [72,73].”
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“This pathway involves the transfer of LPS by the phospholipid transfer protein (PLTP) to lipoproteins (LDL, HDL) that neutralize LPS and promote their elimination through the hepatobiliary route [81].”
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“Nevertheless, the effects of selective decontamination on endotoxemia in cardiac surgical patients are controversial [61,62].”
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Dellinger, R., Tomayko, J., Angus, D., Opal, S., Cupo, M., McDermott, S., Ducher, A., Calandra, T., & Cohen, J. (2009) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181b0266c · Cited by 63 · cited 1× · see citing works
“However, this strategy has failed to demonstrate any benefit in patients with gram-negative sepsis [86].”
BackgroundBelančić, A. (2020) · Obesity Medicine · doi:10.1016/j.obmed.2020.100302 · Cited by 59 · cited 1× · see citing works
“Therefore, it has been hypothesized that a shift in gut microbiota could have a major influence upon the consequences of LPS translocation [16].”
BackgroundProlonged Cardiopulmonary Bypass is a Risk Factor for Intestinal Ischaemic Damage and Endotoxaemia.
Adamik, B., Kübler, A., Goździk, A., & Goździk, W. (2017) · Heart, Lung and Circulation · doi:10.1016/j.hlc.2016.10.012 · Cited by 58 · cited 2× · see citing works
“Visceral ischemia reperfusion caused by damaging gut mucosa and enterocytes [34] increases permeability, including for large molecules [27], and promotes endotoxemia.”
BackgroundGut Microbiota in Heart Failure Patients With Preserved Ejection Fraction (GUMPTION Study)
Huang, Z., Mei, X., Jiang, Y., Chen, T., & Zhou, Y. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.803744 · Cited by 54 · see citing works
Therapeutic Potential of the Gut Microbiota in the Management of Sepsis
Bassetti, M., Bandera, A., & Gori, A. (2020) · Critical Care · doi:10.1186/s13054-020-2780-3 · Cited by 52 · see citing works
Piton, G., Gouge, A. L., Brulé, N., Cypriani, B., Lacherade, J., Nseir, S., Mira, J., Mercier, E., Sirodot, M., Rigaud, J., et al. (2019) · Intensive Care Medicine · doi:10.1007/s00134-019-05649-3 · Cited by 51 · cited 1× · see citing works
“For instance, in critically ill patients, enteral nutrition might prevent mucosa atrophy and help restore enterocyte mass [64].”
BackgroundCatecholamine Use is Associated With Enterocyte Damage in Critically Ill Patients
Piton, G., Cypriani, B., Regnard, J., Patry, C., Puyraveau, M., & Capellier, G. (2015) · Shock · doi:10.1097/shk.0000000000000327 · Cited by 48 · cited 1× · see citing works
“Although we did not find any comparison between patients with and without cardiogenic shock, higher I-FABP has been reported in patients with shock and patients requiring catecholamine [38,39].”
ResultDoudakmanis, C., Bouliaris, K., Kolla, C., Efthimiou, M., & Koukoulis, G. (2021) · World Journal of Gastrointestinal Pathophysiology · doi:10.4291/wjgp.v12.i6.106 · Cited by 36 · cited 1× · see citing works
“Selective digestive decontamination, prebiotic, probiotic administration and fecal transplantation have been described as means of modulating the gut microbiota [58,59] Gut microbiota has been associated with inflammation in patients with heart failure [60].”
BackgroundGautier, T., Deckert, V., Nguyen, M., Desrumaux, C., Masson, D., & Lagrost, L. (2021) · Pharmacology and Therapeutics · doi:10.1016/j.pharmthera.2021.108105 · Cited by 35 · cited 2× · see citing works
“LPS bound to lipoproteins are inactivated (it cannot riggers TLR-4 response) [23].”
BackgroundSelf-citationDeckert, V., Lemaire, S., Ripoll, P., de Barros, J., Labbé, J., Borgne, C. L., Turquois, V., Maquart, G., Larose, D., Desroche, N., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-03285-9 · Cited by 34 · cited 1×
“Accordingly, the administration of recombinant PLTP has been demonstrated to improve survival in animals models of endotoxemia [87].”
BackgroundSelf-citationYassin, M. M. I., D'Sa, A. A. B. B., Parks, T., Soong, C., Halliday, M., Mccaigue, M., Erwin, P., & Rowlands, B. (1998) · British Journal of Surgery · doi:10.1046/j.1365-2168.1998.00717.x · Cited by 32 · cited 2×
“Interestingly, it has been reported that ischemia-reperfusion of the lower limbs may alter gut structure and permeability, resulting in potential gut barrier dysfunction even though the primary injury does not affect the digestive tract [33].”
BackgroundT cell dysregulation in inflammatory diseases in ICU
Luperto, M., & Zafrani, L. (2022) · Intensive Care Medicine Experimental · doi:10.1186/s40635-022-00471-6 · Cited by 32 · see citing works
Serum Zonulin and Endotoxin Levels in Exceptional Longevity versus Precocious Myocardial Infarction
Carrera-Bastos, P., Picazo, Ó., Fontes-Villalba, M., Pareja-Galeano, H., Lindeberg, S., Martínez-Sellés, M., Lucia, A., & Emanuele, E. (2018) · Aging and Disease · doi:10.14336/ad.2017.0630 · Cited by 31 · cited 1× · see citing works
“Indeed, patients with myocardial infarction had higher serum level of LPS and zonulin (a protein that regulates intestinal barrier function [44] and could be used to assess gut permeability [45]) than healthy centenarians [46].”
BackgroundKastl, S., Krychtiuk, K. A., Lenz, M. W., Distelmaier, K., Goliasch, G., Huber, K., Wojta, J., Heinz, G., & Speidl, W. S. (2018) · Shock · doi:10.1097/shk.0000000000001195 · Cited by 29 · cited 1× · see citing works
“During cardiogenic shock, I-FABP was reported to be higher at ICU admission in non-survivors than in survivors [37].”
BackgroundThe role of gut dysbiosis-associated inflammation in heart failure
Francisqueti-Ferron, F., Nakandakare-Maia, E. T., Siqueira, J., Ferron, A., Vieira, T. A., Bazan, S., & Corrêa, C. (2022) · Revista da Associação Médica Brasileira · doi:10.1590/1806-9282.20220197 · Cited by 28 · see citing works
Giménez-Esparza, C., Portillo-Requena, C., Colomina-Climent, F., Allegue-Gallego, J. M., Galindo-Martínez, M., Mollà-Jiménez, C., Antón-Pascual, J. L., Mármol-Peis, E., Dólera-Moreno, C., Rodríguez-Serra, M., et al. (2019) · BMJ Open · doi:10.1136/bmjopen-2019-030139 · Cited by 28 · cited 1×
“Indeed, two RCTs that focused on plasma filtration and adsorption of cytokines in septic shock patients were interrupted prematurely due to possible harmful effects [72,73].”
BackgroundNguyen, M., Tavernier, A., Gautier, T., Aho, S., Morgant, M., Bouhemad, B., Guinot, P., & Grober, J. (2020) · Cytokine · doi:10.1016/j.cyto.2020.155182 · Cited by 24 · cited 1× · see citing works
“Similarly, in patients undergoing cardiac surgery with cardiopulmonary bypass, there was no correlation between I-FABP and LPS measured by mass spectrometry [41].”
BackgroundSelf-citationDargent, A., de Barros, J.-P. P., Ksiazek, E., Fournel, I., Dusuel, A., Rérole, A., Choubley, H., Masson, D., Lagrost, L., & Quenot, J. (2019) · Intensive Care Medicine · doi:10.1007/s00134-019-05749-0 · Cited by 21 · cited 1×
“The few studies that assessed endotoxemia activity suggested a low incidence of endotoxemia in this population, but the correlation between LPS mass and activity was weak [55].”
BackgroundSelf-citationKiers, D., Leijte, G., Gerretsen, J., Zwaag, J., Kox, M., & Pickkers, P. (2019) · Innate Immunity · doi:10.1177/1753425918819754 · Cited by 16 · cited 1× · see citing works
“More specifically, after TLR-4 activation, LPS activate pro-inflammatory pathways, resulting in endothelial dysfunction, coagulopathy, and cardiovascular dysfunction [10,11].”
BackgroundSeptic Participation in Cardiogenic Shock: Exposure to Bacterial Endotoxin
Ramírez, P., Villarreal, E., Gordon, M., Gómez, M., de Hevia, L., Vacacela, K., Gisbert, T., Quinzá, A., Ruíz, J., Alonso, R., et al. (2017) · Shock · doi:10.1097/shk.0000000000000798 · Cited by 15 · cited 1×
“However, the actual endotoxins were not measured, and the antibody titer, which provides only indirect assessment of endotoxemia, was not associated with mortality [52].”
BackgroundNguyen, M., Pallot, G., Jalil, A., Tavernier, A., Dusuel, A., Guern, N. L., Lagrost, L., de Barros, J.-P. P., Choubley, H., Bergas, V., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.622935 · Cited by 14 · cited 4× · see citing works
“systemic circulation by exerting a first hepatic pass effect [24].”
BackgroundInfluentialSelf-citationPickkers, P., & van der Poll, T. (2018) · Intensive Care Medicine · doi:10.1007/s00134-018-5462-8 · Cited by 12 · cited 1× · see citing works
“Therefore, the “one-sizefits-all” concept applies poorly to immunology, and personalizing treatments will probably be necessary [90].”
BackgroundFrea, S., Bovolo, V., Pidello, S., Canavosio, F. G., Botta, M., Bergerone, S., & Gaita, F. (2015) · International Journal of Cardiology · doi:10.1016/j.ijcard.2015.05.061 · Cited by 11 · cited 1×
“More available biomarkers, such as ammonia, have been proposed as markers of abdominal injury in patients with heart failure [43].”
BackgroundNader, N., Asgeri, M., Davari-Farid, S., Pourafkari, L., Ahmadpour, F., Porhomayon, J., Javadzadeghan, H., Negargar, S., & Knight, P. (2015) · Journal of Cardiovascular and Thoracic Research · doi:10.15171/jcvtr.2015.19 · Cited by 9 · cited 1×
“In addition, because LPS-induced cardiac dysfunction has been demonstrated to be dose-dependent in animal models [7], the extrapolation of one disease to another might not be straightforward.”
BackgroundAndrei, S., Nguyen, M., Berthoud, V., Morgant, M., Bouhemad, B., & Guinot, P. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.738496 · Cited by 8
Self-citationThe impact of endotoxin on jejunal tissue oxygenation
Pajk, W., Stadlbauer, K., Kleinsasser, A., Kotzinger, O., Ulmer, H., Hasibeder, W., & Knotzer, H. (2017) · Microcirculation · doi:10.1111/micc.12379 · Cited by 8 · cited 2× · see citing works
“[3] and mucosal gut oxygenation [32], which might create a vicious cycle (Figure 1).”
BackgroundLee, C.-T., Wang, C.-H., Chan, W.-S., Tsai, Y.-Y., Wei, T., Lai, C., Wang, M.-J., Chen, Y.-S., & Yeh, Y. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.772413 · Cited by 4 · cited 2×
“Quantitative measurement None Activity measurement EAA [53] Low (6%) EAA [54] Low (9%)”
BackgroundEndotoxin role in cardiogenic shock: a brief report.
Attaná, P., Lazzeri, C., Chiostri, M., Picariello, C., Gensini, G., & Valente, S. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2012.11.100 · Cited by 3 · cited 2×
“Quantitative measurement None Activity measurement EAA [53] Low (6%) EAA [54] Low (9%)”
Background
Flagged first, then by citations
4 of the 92 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
- [6]Sivarajan M. Amory D.W. Effects of glucagon on regional blood flow during cardiogenic shock Circ. Shock 1979 6 365 373 Available online: https://europepmc.org/article/med/119586 (accessed on 17 May 2022) 119586
- [12]Singer M. Deutschman C.S. Seymour C.W. Shankar-Hari M. Annane D. Bauer M. Bellomo R. Bernard G.R. Chiche J.-D. Coopersmith C.M. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) JAMA 2016 315 801 10.1001/jama.2016.0287 26903338 PMC4968574 · DOI · Paper page
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Cited by
Sorted by citations
Matacchione, G., Piacenza, F., Pimpini, L., Rosati, Y., & Marcozzi, S. (2024) · Clinical Epigenetics · doi:10.1186/s13148-024-01786-9 · Cited by 41 · see citing works
Кологривова, И. В., Керчева, М. А., Panteleev, O. O., & Ryabov, V. V. (2024) · Biomedicines · doi:10.3390/biomedicines12092073 · Cited by 28 · see citing works
“…facilitating the penetration of bacterial components into the systemic bloodstream, the emergence of endotoxinemia, and the onset of infection [60] (Figure 2). increases, penetration of bacterial components into the systemic bloodstream, the emergence en-dotoxinemia, and the onset of…”
BackgroundGut Microbiota in Heart Failure—The Role of Inflammation
Fountoulakis, P. N., Theofilis, P., Vlachakis, P. K., Karakasis, P., Pamporis, K., Sagris, Μ., Dimitroglou, Y., Tsioufis, P., Oikonomou, E. K., Tsioufis, K. P., et al. (2025) · Biomedicines · doi:10.3390/biomedicines13040911 · Cited by 23 · see citing works
“In fact, Nguyen et al. suggest that almost half of the population hospitalized for acute HF had excessive endotoxin levels and acidosis of the intestinal mucosal cells [92].”
Vasoplegia Syndrome After Cardiac Surgery
Castagna, F., Mehra, M. R., Nabzdyk, C. S., & Givertz, M. M. (2025) · JACC Heart Failure · doi:10.1016/j.jchf.2025.02.028 · Cited by 15 · see citing works
Gastrointestinal function and nutritional interventions in septic shock
Bachmann, K. F., Cotoia, A., & Reintam Blaser, A. (2025) · Current Opinion in Critical Care · doi:10.1097/mcc.0000000000001302 · Cited by 13 · see citing works
Exertional Stress-induced Pathogenic Luminal Content Translocation – Friend or Foe?
Henningsen, K., Martinez, I. G., & Costa, R. J. S. (2023) · International Journal of Sports Medicine · doi:10.1055/a-2235-1629 · Cited by 12 · see citing works
“Under-standably, if endotoxemia is left unaddressed and progresses into thrombus formation, subsequent cellular death, and multiple organ failure, then the risk of septic shock and/or mortality is drastically enhanced [33, 34].”
BackgroundKo, R., Choi, K. H., Lee, K., Jeon, J., Jang, H., Chung, C., Cho, Y. H., Park, T., Lee, J., Song, Y.-B., et al. (2025) · Critical Care · doi:10.1186/s13054-025-05495-4 · Cited by 9 · see citing works
“The role of endotoxemia in CS pathophysiology has recently gained attention, with evidence suggesting that it originates from gut barrier dysfunction [16, 17].”
Shokravi, A., Luo, Y., & Rabkin, S. W. (2025) · Cells · doi:10.3390/cells14141124 · Cited by 9 · see citing works
“Clinically, LPS levels increase significantly during decompensated HF episodes, likely due to splanchnic venous congestion, and decrease with successful decongestion [74,75].”
Nendl, A., Andersen, G., Seljeflot, I., Trøseid, M., & Awoyemi, A. (2024) · Open Heart · doi:10.1136/openhrt-2024-002868 · Cited by 8 · see citing works
“27 LPS in the blood is found in biologically active (e.g., monomers or micelles) and inactive forms (e.g., bound to lipoproteins).”
Nguyen, M., Alvarez, M., Evezard, C., Berthoud, V., Leleu, D., Pais-de-Barros, J., Bouchot, O., Abou-Arab, O., Bouhemad, B., Masson, D., et al. (2025) · Annals of Intensive Care · doi:10.1186/s13613-025-01499-z · Cited by 7
“However, data on LPS translocation in cardiogenic shock patients are scarce [24].”
Self-citationGut Microbiota Alterations in Heart Failure Patients: Insights from a Systematic Review
Báez‐Ferrer, N., Lemus-Martín, A., Castro-Hernández, M. B., y, P. A., González, S. M., Lecuona, M., & Domínguez‐Rodríguez, A. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14228110 · Cited by 6 · see citing works
Nguyen, M., Alvarez, M., Evezard, C., Ibrahima, A., Huette, P., Mahjoub, Y., Pais-de-Barros, J., Bouhemad, B., Masson, D., Gautier, T., et al. (2026) · European Journal of Anaesthesiology · doi:10.1097/eja.0000000000002350 · Cited by 3 · see citing works
Self-citationAmil, M. A., Koo, J.-H., Yah, X., Salam, N. A., & Zakaria, M. M. (2026) · GERMS · doi:10.3390/germs16020009 · Cited by 1
“Human exposure to microbial biotoxins, e.g., endotoxin, cytotoxin, and mycotoxins, has been associated with diverse adverse outcomes, such as septic shock [49], organ failures [50], chronic inflammation [51], hepatotoxicity [52], carcinogenesis [53,54], and alterations in metabolic pathways [55].”
Omar, A. (2026) · Journal of Artificial Organs · doi:10.1007/s10047-025-01543-6 · Cited by 1
Risk factors and prognostic value of endotoxemia in patients with acute myocardial infarction
Nguyen, M., Putot, A., Masson, D., Cottin, Y., Gautier, T., Tribouillard, L., Rérole, A., Guinot, P., Maza, M., de Barros, J.-P. P., et al. (2024) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2024.1419001 · Cited by 1
Self-citationChong, L., Rampersaud, H., Rao, D. A., Gujare, I., Makhijani, A., Kim, D., Levy, E., Beatty, B. L., & Kobayashi, S. (2026) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00584.2026
Gavate, S., Mohite, A., & Pathade, G. (2026) · Adolescência e Saúde · doi:10.67440/ahj.v21i4s.1157
“Endotoxic shock may be amenable to focused therapy by extracorporeal blood purification [15].”
InfluentialHonoré, P., Benkaddour, Y., Lissnyder, N. D., Khouja, R. B., & Muscato, C. (2026) · Critical Care · doi:10.1186/s13054-026-06052-3
“While endotoxin exposure can indeed induce cardiovascular dysfunction resembling septic shock, including reduced ejection fraction, ventricular dilatation, and decreased systemic vascular resistance [7, 8], its direct myocardial impact in cardiogenic shock remains uncertain.”
Mécanismes de base de la physiopathologie du choc cardiogénique
Molkhou, C., & Besnier, E. (2026) · Archives des Maladies du Coeur et des Vaisseaux - Pratique · doi:10.1016/j.amcp.2026.03.004
Hemoadsorption in cardiac surgery with cardiopulmonary bypass
Monard, C., Lemagnen, I., Abraham, P., Palluau, M., Moulin, C., Marcucci, C., Kirsch, M., & Schneider, A. (2025) · Journal of Translational Critical Care Medicine · doi:10.1097/jtccm-d-25-00002
- Authors
- Nguyen, M., Gautier, T., Masson, D., Bouhemad, B., & Guinot, P.-G.
- Affiliations
- Inserm (FR)
- Department of Anesthesiology and Intensive Care, Dijon University Hospital, F-21000 Dijon, France
- Corresponding author
- Nguyen, Maxime
- Venue
- Journal of Clinical Medicine
- Publisher
- MDPI AG
- Published
- 2023-03-29
- Volume
- 12
- Issue
- 7
- Pages
- 2579
- ISSN
- 2077-0383 (ISSN-L)
- PMC
- PMC10094881
- OpenAlex
- W4361278065
- Cited by
- 25
- References
- 92
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 7
- FWCI
- 0.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Clinical Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- departmental sources and the program “Investissements d’Avenir” (ANR-11-LABX-0021)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Physical Sciences › Engineering › Biomedical Engineering › Mechanical Circulatory Support Devices
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- endotoxemia, acute heart failure, cardiogenic shock, intestinal barrier dysfunction, intestinal injury, organ dysfunction, personalized treatment, vicious circle
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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