Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jun 6:10:1138352.
doi: 10.3389/fcvm.2023.1138352. eCollection 2023.

Association of GSDMD with microvascular-ischemia reperfusion injury after ST-elevation myocardial infarction

Wenjing Sun #  1   2 , Chunqiu Wang #  3 , Shihua Cui #  4 , Yan Wang  3 , Shenghui Zhao  1 , Min Lu  1 , Fan Yang  5 , Shujuan Dong  1 , Yingjie Chu  1
Affiliations

Association of GSDMD with microvascular-ischemia reperfusion injury after ST-elevation myocardial infarction

Wenjing Sun et al. Front Cardiovasc Med. .

Abstract

Objectives: Little is known about the clinical prognosis of gasdermin D (GSDMD) in patients with ST-elevation myocardial infarction (STEMI). The purpose of this study was to investigate the association of GSDMD with microvascular injury, infarction size (IS), left ventricular ejection fraction (LVEF), and major adverse cardiac events (MACEs), in STEMI patients with primary percutaneous coronary intervention (pPCI).

Methods: We retrospectively analyzed 120 prospectively enrolled STEMI patients (median age 53 years, 80% men) treated with pPCI between 2020 and 2021 who underwent serum GSDMD assessment and cardiac magnetic resonance (CMR) within 48 h post-reperfusion; CMR was also performed at one year follow-up.

Results: Microvascular obstruction was observed in 37 patients (31%). GSDMD concentrations ≧ median (13 ng/L) in patients were associated with a higher risk of microvascular obstruction and IMH (46% vs. 19%, P = 0.003; 31% vs. 13%, P = 0.02, respectively), as well as with a lower LVEF both in the acute phase after infarction (35% vs. 54%, P < 0.001) and in the chronic phase (42% vs. 56%, P < 0.001), larger IS in the acute (32% vs. 15%, P < 0.001) and in the chronic phases (26% vs. 11%, P < 0.001), and larger left ventricular volumes (119 ± 20 vs. 98 ± 14, P = 0.003) by CMR. Univariable and multivariable Cox regression analysis results showed that patients with GSDMD concentrations ≧ median (13 ng/L) had a higher incidence of MACE (P < 0.05).

Conclusions: High GSDMD concentrations in STEMI patients are associated with microvascular injury (including MVO and IMH), which is a powerful MACE predictor. Nevertheless, the therapeutic implications of this relation need further research.

Keywords: GSDMD; IMH; MVO; ST-segment elevation myocardial infarction; magnetic resonance imaging; microvascular dysfunction.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of the cohort study.
Figure 2
Figure 2
Association of GSDMD with LVEF, IS, T2*maps and MVO. LVEF, left ventricular ejection fraction; IS, infarction size; MVO, microvascular obstruction.
Figure 3
Figure 3
CMR images from two patients with STEMI treated by PPCI. Short axis slices in the basal, middle and apical region and long axis long axis two-chamber heart are showed. Patient A: A 57-year-old patient with anterior STEMI treated by PPCI and with GSDMD concentrations ≧ median (13 ng/L). The CMR images on day 2 showing transmural infarction in the anterior wall with MVO, and the Native T1 and T2* maps represent myocardial damage and intramyocardial hemorrhage. Patient B: A 49-year-old patient with lateral STEMI treated by pPCI and with GSDMD concentrations< median (13ng/L). The CMR images on day 2 manifesting infarction in the lateral wall with MVO, and the Native T1 and T2* maps represent myocardial damage and intramyocardial hemorrhage.
Figure 4
Figure 4
Receiver operating characteristic curve for the prediction of death in hospital in STEMI patients.
Figure 5
Figure 5
Kaplan-Meier curves suggesting the risk of MACE in relation to GSDMD concentrations compared to GRACE score. MACE, major adverse cardiac events; GSDMD, gasdermin D.
Figure 6
Figure 6
Kaplan-Meier curves according to GSDMD optimal cutoff values for predicting MACE. (A) Receiver operating characteristic curve for the prediction optimal cutoff values of GSDMD and for prediction microvascular dysfunction diagnosis. (B) High concentration of GSDMD correlated with poor outcomes in STEMI patients.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Mozaffarian D, Benjamin E, Go A, Arnett D, Blaha M, Cushman M, et al. Executive summary: heart disease and stroke statistics–2016 update: a report from the American heart association. Circulation. (2016) 133(4):447–54. 10.1161/CIR.0000000000000366 - DOI - PubMed
    1. de Waha S, Patel M, Granger C, Ohman E, Maehara A, Eitel I, et al. Relationship between microvascular obstruction and adverse events following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: an individual patient data pooled analysis from seven randomized trials. Eur Heart J. (2017) 38(47):3502–10. 10.1093/eurheartj/ehx414 - DOI - PubMed
    1. Berry C, Ibáñez B. Intramyocardial hemorrhage: the final frontier for preventing heart failure post-myocardial infarction. J Am Coll Cardiol. (2022) 79(1):49–51. 10.1016/j.jacc.2021.11.002 - DOI - PubMed
    1. Heusch G. Coronary microvascular obstruction: the new frontier in cardioprotection. Basic Res Cardiol. (2019) 114(6):45. 10.1007/s00395-019-0756-8 - DOI - PubMed
    1. Ghugre N, Pop M, Thomas R, Newbigging S, Qi X, Barry J, et al. Hemorrhage promotes inflammation and myocardial damage following acute myocardial infarction: insights from a novel preclinical model and cardiovascular magnetic resonance. J Cardiovasc Magn Reson. (2017) 19(1):50. 10.1186/s12968-017-0361-7 - DOI - PMC - PubMed