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. 2025 Nov;5(11):1487-1501.
doi: 10.1016/j.jacasi.2025.07.015. Epub 2025 Sep 5.

Association and Prognostic Implications of "No-Reflow Phenomenon" and Hypercoagulability in Patients With ST-Segment Elevation Myocardial Infarction

Mohamed Omar  1 , Min Gyu Kang  2 , Moon Ki Jung  3 , Jong-Hwa Ahn  4 , Jin-Sin Koh  2 , Phil Iver Guevarra  5 , Sang-Wook Kim  3 , Udaya S Tantry  6 , Paul A Gurbel  6 , Jin-Yong Hwang  2 , Young-Hoon Jeong  7
Affiliations

Association and Prognostic Implications of "No-Reflow Phenomenon" and Hypercoagulability in Patients With ST-Segment Elevation Myocardial Infarction

Mohamed Omar et al. JACC Asia. 2025 Nov.

Abstract

Background: Following percutaneous coronary intervention (PCI), the "no-reflow phenomenon" is associated with a worse outcome. However, it remains unclear how to prevent and treat this phenomenon during PCI.

Objectives: This study aimed to evaluate the association between thrombogenicity profiles and "no-reflow phenomenon" during primary PCI in patients with ST-segment elevation myocardial infarction (STEMI).

Methods: From a real-world registry, we prospectively enrolled patients with STEMI who underwent primary PCI (n = 334). TIMI flow grade was assessed at final angiography, and the "no-reflow phenomenon" was defined as TIMI flow grade between 0 and 2. Thrombogenicity profiles were assessed with thromboelastography (TEG) and conventional hemostatic measurements.

Results: Thirty-seven patients (11.1%) showed no-reflow after primary PCI. High platelet-fibrin clot strength (P-FCS: ≥ 68 mm) measured by TEG was significantly associated with an increased risk of post-PCI "no-reflow phenomenon" (OR: 2.611; 95% CI: 1.220-5.584; P = 0.010). The risk stratification with "no-reflow phenomenon" and "high P-FCS phenotype" appeared to be additive to predict the risk of 3-year clinical event (log-rank P < 0.001 across the groups). Patients with both "no-reflow phenomenon" and high P-FCS had a higher risk of adverse clinical events compared with normal-reflow subjects with low P-FCS (adjusted HR: 6.654; 95% CI: 2.678-16.530; P < 0.001).

Conclusions: This study demonstrated a close relationship between heightened thrombogenicity (assessed by TEG P-FCS) with "no-reflow phenomenon," and their additive prognostic implications after primary PCI in STEMI patients. Effective control of clot strength may reduce the risk of "no-reflow phenomenon" and improve clinical outcomes in these patients. (Gyeongsang National University Hospital Registry [GNUH]; NCT04650529).

Keywords: acute myocardial infarction; cardiovascular event; clot strength; no-reflow phenomenon; percutaneous coronary intervention.

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Conflict of interest statement

Funding Support and Author Disclosures This research was supported by the Chung-Ang University Research Grants. The content is solely the responsibility of the authors and does not necessarily represent the official views of any funding agencies. The sponsors played no role in this study. There was no industry involvement in the design or conduct of the study; the collection, management, analysis, and interpretation of the data; the preparation, review, and approval of the manuscript; or the decision to submit the manuscript for publication. Dr Gurbel has received grants and personal fees from Bayer HealthCare, Otitopic, Amgen, Janssen, and US WorldMeds; grants from Instrumentation Laboratory, Hikari Dx, Haemonetics, Medicure, and Idorsia Pharmaceuticals; and personal fees from UpToDate; and has patents “Detection of Restenosis Risk in Patients Issued” and “Assessment of Cardiac Health and Thrombotic Risk in a Patient.” Dr Jeong has received honoraria for lectures from Daiichi-Sankyo, Sanofi-Aventis, Hanmi Pharmaceuticals, and Daewoong Pharmaceuticals; and research grants or support from Samjin Pharmaceuticals, Hanmi Pharmaceuticals, Yuhan Pharmaceuticals, Biotronik Korea, and U and I Corporation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
TEG Measurement The figure illustrates the key parameters of a thromboelastography (TEG) tracing, which are measured throughout the entire process of clot formation, stabilization, and dissolution. K = coagulation time; LY30 = percentage of the clot that has lysed 30 minutes after the time of MA; MA = maximum amplitude; P-FCS = platelet-fibrin clot strength; R = reaction time.
Figure 2
Figure 2
Flow Diagram of the Study A total of 334 patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) were enrolled during the study period. Patients were categorized based on post-PCI TIMI flow grade and the level of maximum amplitude (MA) measured by thromboelastography. Clinical outcomes were tracked over a 3-year follow-up period.
Figure 3
Figure 3
Association Between P-FCS and “No-Reflow Phenomenon” (A) Incidence of “no-reflow phenomenon” according to quartile stratification of P-FCS. (B) Receiver-operating characteristic curve analysis: the optimal cutoff of P-FCS for “no-reflow phenomenon.” (C) Risk of “no-reflow phenomenon” according to P-FCS phenotype. AUC = area under the curve; ROC = receiver-operating characteristic; other abbreviation as in Figure 1.
Figure 4
Figure 4
Kaplan-Meier Curves of 3-Year MACE (A) Groups according to “no-reflow phenomenon.” (B) Groups divided by “high P-FCS phenotype” and “no-reflow phenomenon.” MACE = major adverse cardiovascular event; other abbreviation as in Figure 1.
Central Illustration
Central Illustration
Association Between Hemostatic Measurements and “No-reflow Phenomenon” Following Primary Percutaneous Coronary Intervention For patients presenting with first-time STEMI within the first 12 hours from the onset of symptoms (n = 334), hemostatic measurements including thromboelastography (TEG) were performed using preprocedural blood sampling. After primary PCI, TIMI flow grading was evaluated by 2 independent experienced interventional cardiologists blinded to the results of laboratory measures. The presence of “high P-FCS phenotype” (maximal amplitude by TEG ≥68 mm) significantly increased the risk of post-PCI “no-reflow phenomenon” (epicardial coronary flow with TIMI flow grade between 0 and 2) by 2.6-fold. The risk stratification based on “no-reflow phenomenon” and “high P-FCS phenotype” was found to be additive to predict the rate of 3-year MACE (log-rank P < 0.001 across the groups). Presence of “high P-FCS phenotype” did not increase the risk of MACE occurrence in patients with normal-reflow (adjusted HR: 0.886; 95% CI: 0.379-2.075; P = 0.781), whereas this phenotype was significantly associated with an increased rate of MACE in individuals having no-reflow (adjusted HR: 2.566; 95% CI: 1.241-5.303; P = 0.043). Effective control of P-FCS may reduce the risk of the “no-reflow phenomenon” and improve clinical outcomes in STEMI patients; this hypothesis warrants evaluation in large-scale clinical trials. aPTT = activated partial thromboplastin time; CK-MB = creatine phosphokinase-myocardial band; CRP = C-reactive protein; DES = drug-eluting stent; MACE = major adverse cardiovascular event; NT-proBNP = N-terminal pro–B-type natriuretic peptide; PCI = percutaneous coronary intervention; P-FCS = platelet-fibrin clot strength; PT = prothrombin time; STEMI = ST-segment elevation myocardial infarction.
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