Serum Ceramides as Prognostic Biomarkers of Large Thrombus Burden in Patients with STEMI: A Micro-Computed Tomography Study

Efstratios Karagiannidis, Andreas S Papazoglou, Nikolaos Stalikas, Olga Deda, Eleftherios Panteris, Olga Begou, Georgios Sofidis, Dimitrios V Moysidis, Anastasios Kartas, Evangelia Chatzinikolaou, Kleoniki Keklikoglou, Andreana Bompoti, Helen Gika, Georgios Theodoridis, Georgios Sianos, Efstratios Karagiannidis, Andreas S Papazoglou, Nikolaos Stalikas, Olga Deda, Eleftherios Panteris, Olga Begou, Georgios Sofidis, Dimitrios V Moysidis, Anastasios Kartas, Evangelia Chatzinikolaou, Kleoniki Keklikoglou, Andreana Bompoti, Helen Gika, Georgios Theodoridis, Georgios Sianos

Abstract

ST-elevation myocardial infarction (STEMI) remains one of the leading causes of mortality worldwide. The identification of novel metabolic and imaging biomarkers could unveil key pathophysiological mechanisms at the molecular level and promote personalized care in patients with acute coronary syndromes. We studied 38 patients with STEMI who underwent primary percutaneous coronary intervention and thrombus aspiration. We sought to correlate serum ceramide levels with micro-CT quantified aspirated thrombus volume and relevant angiographic outcomes, including modified TIMI thrombus grade and pre- or post-procedural TIMI flow. Higher ceramide C16:0 levels were significantly but weakly correlated with larger aspirated thrombus volume (Spearman r = 0.326, p = 0.046), larger intracoronary thrombus burden (TB; p = 0.030) and worse pre- and post-procedural TIMI flow (p = 0.049 and p = 0.039, respectively). Ceramides C24:0 and C24:1 were also significantly associated with larger intracoronary TB (p = 0.008 and p = 0.001, respectively). Receiver operating characteristic analysis demonstrated that ceramides C24:0 and C24:1 could significantly predict higher intracoronary TB (area under the curve: 0.788, 95% CI: 0.629-0.946 and 0.846, 95% CI: 0.706-0.985, respectively). In conclusion, serum ceramide levels were higher among patients with larger intracoronary and aspirated TB. This suggests that quantification of serum ceramides might improve risk-stratification of patients with STEMI and facilitate an individualized approach in clinical practice.

Keywords: ST-elevation myocardial infarction; ceramides; micro-CT; thrombus; thrombus aspiration.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
3-D volume rendering of a thrombus using the Skyscan 1172 micro-CT scanner at Hellenic Centre for Marine Research. The clot was stained using 0.3% phosphotungstic acid as a contrast agent. Projection images were reconstructed into sections (cross-section images) via NRecon (Bruker, Kontich, Belgium) software.
Figure 2
Figure 2
(A) Serum ceramide C16:0 levels were positively correlated with larger aspirated thrombus volume. (B) The median C16:0 level of patients with TIMI thrombus Grade 4 was higher compared to the corresponding levels of patients with lower TIMI thrombus Grades (2 and 3). (C) The median C16:0 levels were higher in patients with worse pre-procedural TIMI flow.
Figure 3
Figure 3
ROC curve analysis. Receiver-operating characteristic curve analysis of thrombus grade diagnosed by ceramide C16:0, C18:0, C24:0 and C24:1 levels.

References

    1. Chalikias G., Kikas P., Thomaidis A., Serif L., Georgiadis G.S. Tziakas, D. A patient with an extensive coronary artery thrombus. Hell. J. Cardiol. 2018;59:347–348. doi: 10.1016/j.hjc.2017.11.002.
    1. Yip H.-K., Chen M.-C., Chang H.-W., Hang C.-L., Hsieh Y.-K., Fang C.-Y., Wu C.-J. Angiographic morphologic features of infarct-related arteries and timely reperfusion in acute myocardial infarction: Predictors of slow-flow and no-reflow phenomenon. Chest. 2002;122:1322–1332. doi: 10.1378/chest.122.4.1322.
    1. Henriques J.P.S., Zijlstra F., Ottervanger J.P., de Boer M.-J., van’t Hof A.W.J., Hoorntje J.C.A., Suryapranata H. Incidence and clinical significance of distal embolization during primary angioplasty for acute myocardial infarction. Eur. Heart J. 2002;23:1112–1117. doi: 10.1053/euhj.2001.3035.
    1. Canfield J., Totary-Jain H. 40 years of percutaneous coronary intervention: History and future directions. J. Pers. Med. 2018;8:33. doi: 10.3390/jpm8040033.
    1. Neumann F.J., Sousa-Uva M., Ahlsson A., Alfonso F., Banning A.P., Benedetto U., Byrne R.A., Collet J.P., Falk V., Head S.J., et al. 2018 ESC/EACTS guidelines on myocardial revascularization. Eur. Heart J. 2019;40:87–165. doi: 10.1093/eurheartj/ehy394.
    1. Napodano M., Dariol G., Al Mamary A.H., Marra M.P., Tarantini G., D’Amico G., Frigo A.C., Buja P., Razzolini R., Iliceto S. Thrombus burden and myocardial damage during primary percutaneous coronary in-tervention. Am. J. Cardiol. 2014;113:1449–1456. doi: 10.1016/j.amjcard.2014.01.423.
    1. Tousoulis D. Novel risk factors in coronary artery disease: Are they clinically relevant? Hell. J. Cardiol. 2019;60:149–151. doi: 10.1016/j.hjc.2019.06.003.
    1. Ichi I., Nakahara K., Miyashita Y., Hidaka A., Kutsukake S., Inoue K., Maruyama T., Miwa Y., Harada-Shiba M., Tsushima M., et al. Association of ceramides in human plasma with risk factors of atherosclerosis. Lipids. 2006;41:859–863. doi: 10.1007/s11745-006-5041-6.
    1. Meeusen J.W., Donato L.J., Kopecky S.L., Vasile V.C., Jaffe A.S., Laaksonen R. Ceramides improve atherosclerotic cardiovascular disease risk assessment beyond standard risk factors. Clin. Chim. Acta. 2020;511:138–142. doi: 10.1016/j.cca.2020.10.005.
    1. Pan W., Dong H., Sun R., Zhao L., Sun M., Li L., Yu X., Liu J., Wu J., Yang F., et al. Plasma ceramides in relation to coronary plaque characterization determined by optical coherence tomography. J. Cardiovasc. Transl. Res. 2020:1–10. doi: 10.1007/s12265-020-09978-3.
    1. Anagnostopoulos C.D., Siogkas P.K., Liga R., Benetos G., Maaniitty T., Sakellarios A.I., Koutagiar I., Karakitsios I., Papafaklis M.I., Berti V., et al. Characterization of functionally significant coronary artery disease by a coronary computed tomography angiography-based index: A comparison with positron emission tomography. Eur. Heart J. Cardiovasc. Imaging. 2019;20:897–905. doi: 10.1093/ehjci/jey199.
    1. Kafouris P.P., Koutagiar I.P., Georgakopoulos A.T., Spyrou G.M., Visvikis D., Anagnostopoulos C.D. Fluorine-18 fluorodeoxyglucose positron emission tomography-based textural features for prediction of event prone carotid atherosclerotic plaques. J. Nucl. Cardiol. 2019:1–11. doi: 10.1007/s12350-019-01943-1.
    1. Vavuranakis M., Papaioannou T.G., Vrachatis D., Katsimboulas M., Sanidas E.A., Vaina S., Agrogiannis G., Patsouris E., Kakadiaris I., Stefanadis C., et al. Computational imaging of aortic vasa vasorum and neo-vascularization in rabbits using contrast-enhanced intravascular ultrasound: Association with histo-logical analysis. Anatol. J. Cardiol. 2018;20:117–124.
    1. Papaioannou T.G., Manolesou D., Dimakakos E., Tsoucalas G., Vavuranakis M., Tousoulis D. 3D bioprinting methods and techniques: Applications on artificial blood vessel fabrication. Acta Cardiol. Sin. 2019;35:284–289.
    1. Karagiannidis E., Sofidis G., Stalikas N., Koletsa T., Kartas A., Keklikoglou K., Chatzinikolaou E., Kangelidis I., Barmpas A., Deligiannis G., et al. Rationale and design of a prospective, single-arm trial for the evaluation of safety and feasibility of large thrombus burden aspiration in the context of ST elevation myocardial infarction. Hell. J. Cardiol. 2020 doi: 10.1016/j.hjc.2020.04.002.
    1. Karagiannidis E., Konstantinidis N.V., Sofidis G., Chatzinikolaou E., Sianos G. Rationale and design of a prospective, observational study for the QUantitative EStimation of Thrombus burden in patients with ST-Elevation Myocardial Infarction using micro-computed tomography: The QUEST-STEMI trial. BMC Cardiovasc. Disord. 2020;20:125. doi: 10.1186/s12872-020-01393-5.
    1. Karagiannidis E., Sofidis G., Papazoglou A.S., Deda O., Panteris E., Moysidis D.V., Stalikas N., Kartas A., Papadopoulos A., Stefanopoulos L., et al. Correlation of the severity of coronary artery disease with patients’ metabolic profile- rationale, design and baseline patient characteristics of the CorLipid Trial. BMC Cardiovasc. Disord. 2021 doi: 10.1186/s12872-021-01865-2.
    1. Sianos G., Papafaklis M.I., Serruys P.W. Angiographic thrombus burden classification in patients with ST-segment elevation myocardial infarction treated with percutaneous coronary intervention. J. Invasive Cardiol. 2010;22:6–14.
    1. Jolly S.S., James S.K., Džavík V., Cairns J.A., Mahmoud K.D., Zijlstra F., Yusuf S., Olivecrona G.K., Renlund H., Gao P., et al. Thrombus aspiration in ST elevation myocardial infarction: An individual patient meta-analysis. Circulation. 2016;135:143–152. doi: 10.1161/CIRCULATIONAHA.116.025371.
    1. Fröbert O., Calais F., James S.K., Lagerqvist B. ST-elevation myocardial infarction, thrombus aspiration, and different invasive strategies. A TASTE trial substudy. J. Am. Heart Assoc. 2015;4:e001755. doi: 10.1161/JAHA.114.001755.
    1. Fröbert O., Lagerqvist B., Olivecrona G.K., Omerovic E., Gudnason T., Maeng M., Aasa M., Angerås O., Calais F., Danielewicz M., et al. Thrombus aspiration during ST-segment elevation myocardial infarction. N. Engl. J. Med. 2013;369:1587–1597. doi: 10.1056/NEJMoa1308789.
    1. Collet J.-P., Thiele H., Barbato E., Barthélémy O., Bauersachs J., Bhatt D.L., Dendale P., Dorobantu M., Edvardsen T., Folliguet T., et al. 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur. Heart J. 2020:1–79. doi: 10.1093/eurheartj/ehaa575.
    1. Fröhlich G.M., Landmesser U. Thrombus aspiration in STEMI revisited: Impact on coronary microcirculation? Open Hear. 2015;2:e000274. doi: 10.1136/openhrt-2015-000274.
    1. Sardella G., Stio R.E. Thrombus aspiration in acute myocardial infarction: Rationale and indication. World J. Cardiol. 2014;6:924–928. doi: 10.4330/wjc.v6.i9.924.
    1. Pan W., Li L., Sun M., Wang C., Fang S., Yu B. Plasma ceramides are associated with coronary atherosclerotic burden in patients with ST-segment elevation myocardial infarction. Int. J. Cardiol. 2020;320:155–160. doi: 10.1016/j.ijcard.2020.08.010.
    1. Cheng J.M., Suoniemi M., Kardys I., Vihervaara T., de Boer S.P.M., Akkerhuis K.M., Sysi-Aho M., Ekroos K., Garcia-Garcia H.M., Oemrawsingh R.M., et al. Plasma concentrations of molecular lipid species in relation to coronary plaque characteristics and cardiovascular outcome: Results of the ATHERO-REMO-IVUS study. Atherosclerosis. 2015;243:560–566. doi: 10.1016/j.atherosclerosis.2015.10.022.
    1. Li Q., Wang X., Pang J., Zhang Y., Zhang H., Xu Z., Chen Q., Ling W. Associations between plasma ceramides and mortality in patients with coronary artery disease. Atherosclerosis. 2020;314:77–83. doi: 10.1016/j.atherosclerosis.2020.09.004.
    1. Pan W., Sun M., Wu J., Dong H., Liu J., Gao R., Fang S., Xing L., Hu S., Yu B. Relationship between elevated plasma ceramides and plaque rupture in patients with ST-segment elevation myocardial infarction. Atherosclerosis. 2020;302:8–14. doi: 10.1016/j.atherosclerosis.2020.04.008.

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