The Role of Inflammation in the Pathogenesis of Cardiogenic Shock Secondary to Acute Myocardial Infarction: A Narrative Review

Abstract

Cardiogenic shock (CS) is one of the most serious complications of myocardial infarction (MI) with a high mortality rate. The timely and effective prevention and early suppression of this adverse event may influence the prognosis and outcome in patients with MI complicated by CS (MI CS). Despite the use of existing pharmaco-invasive options for maintaining an optimal pumping function of the heart in patients with MI CS, its mortality remains high, prompting the search for new approaches to pathogenetic therapy. This review considers the role of the systemic inflammatory response in the pathogenesis of MI CS. The primary processes involved in its initiation are described, including the progression from the onset of MI to the generalization of the inflammatory response and the development of multiple organ dysfunction. The approaches to anti-inflammatory therapy in patients with CS are discussed, and further promising research directions are outlined. In this review, we updated and summarized information on the inflammatory component of MI CS pathogenesis with a particular focus on its foundational aspects. This will facilitate the identification of specific inflammatory phenotypes and endotypes in MI CS and the development of targeted therapeutic strategies for this MI complication.

Keywords: anti-inflammatory therapy; cardiogenic shock; clonal hematopoiesis; hemoadsorption; inflammation; monocytes; myocardial infarction; myocardial infarction-associated cardiogenic shock; neutrophils; pathophysiology.

Figure 1

Development of inflammation in myocardial infarction. Myocardial injury results in the release of DAMPs from the injured myocardium that cause inflammation through the activation of the complement system, the acute-phase response, and the recruitment of innate immune cells (neutrophils, monocytes, macrophages, and dendritic cells). This is followed by the recruitment of adaptive immune cells (lymphocytes). Moreover, microRNAs are involved in regulating the inflammatory response and its potency. Data from Frangogiannis (2014) [27]; Hofmann et al. (2015) [28]; Li et al. (2016) [29]; Timmermans et al. (2016) [22]; Pluijmert et al. (2021) [25]; Anzai et al. (2022) [23]; Varzideh et al. (2022) [30]; and Zhang et al. (2022) [31]. The icon of bone marrow is created by kerismaker and was downloaded from www.flaticon.com (https://www.flaticon.com/free-icon/bone-marrow_3816804?term=bone+marrow&page=1&position=10&origin=search&related_id=3816804, accessed on 18 August 2024). DAMPs, damage-associated molecular patterns; HMGB1, high-mobility group protein B1; HSP, heat shock protein; MHC II, major histocompatability complex II; miRNA, micro-ribonucleic acid; mtDNA, mitochondrial deoxyribonucleic acid; nDNA, nuclear deoxyribonucleic acid; RNA, ribonucleic acid; S100, S100 protein; TCR, T-cell receptor.

Figure 2

Inflammation development in cardiogenic shock. The decreased cardiac output is associated with hypoperfusion and organ damage. In this case, an increase in damage-associated molecular patterns (DAMPs) is accompanied by an increase in pathogen-associated molecular patterns (PAMPs), which cause the activation and subsequent dysfunction of immune cells. NETosis, the release of granulocyte nucleic acids into the extracellular environment, and clonal hematopoiesis associated with somatic mutations of hematopoietic stem cells are observed. Resuscitation procedures such as extracorporeal membrane oxygenation (ECMO) can also stimulate the dysfunction of immune cells. DAMPs, damage-associated molecular patterns; ECMO, extracorporeal membrane oxygenation; Mφ, macrophage; PAMPs, pathogen-associated molecular patterns; Th, T helper lymphocyte.

Figure 3

The role of immune cells in the development of inflammation during myocardial infarction-associated shock. CD, cluster of differentiation; GDF-15, growth-differentiation factor 15; LMR, lymphocytes-to-monocytes ratio; MCP-1, monocyte chemotactic protein-1; MI CS, myocardial infarction-associated shock; NET, neutrophil extracellular trap; NLR, neutrophils-to-lymphocytes ratio; Th, T helper lymphocyte; Treg, regulatory T lymphocytes; TREM2, triggering receptor expressed on myeloid cells 2.

Figure 4

Modern approaches to control inflammation in cardiogenic shock. CRP, C-reactive protein; CS, cardiogenic shock; IL, interleukin; mAbs, monoclonal antibodies.