key: cord-0973975-p2v4wms6 authors: Kang, Min Gyu; Koo, Bon-Kwon; Tantry, Udaya S.; Kim, Kyehwan; Ahn, Jong-Hwa; Park, Hyun Woong; Park, Jeong Rang; Hwang, Seok-Jae; Hwang, Jin-Yong; Gurbel, Paul A.; Samady, Habib; Koh, Jin-Sin; Jeong, Young-Hoon title: Association Between Thrombogenicity Indices and Coronary Microvascular Dysfunction in Patients With Acute Myocardial Infarction date: 2021-10-25 journal: JACC Basic Transl Sci DOI: 10.1016/j.jacbts.2021.08.007 sha: 097189de6ccdcdeceb7036c0fbf13d370c06bf08 doc_id: 973975 cord_uid: p2v4wms6 The association between thrombogenicity and coronary microvascular dysfunction (CMD) has been poorly explored in patients with acute myocardial infarction (AMI). In our real-world clinical practice (N = 116), thrombogenicity was evaluated with thromboelastography and conventional hemostatic measures, and CMD was defined as index of microcirculatory resistance of >40 U using the invasive physiologic test. High platelet-fibrin clot strength (P-FCS) (≥68 mm) significantly increased the risk of postprocedural CMD (odds ratio: 4.35; 95% CI: 1.74-10.89). Patients with both CMD and high P-FCS had a higher rate of ischemic events compared to non-CMD subjects with low P-FCS (odds ratio: 5.58; 95% CI: 1.31-23.68). This study showed a close association between heightened thrombogenicity and CMD and their prognostic implications after reperfusion in acute myocardial infarction patients. The association between thrombogenicity and coronary microvascular dysfunction (CMD) has been poorly explored in patients with acute myocardial infarction (AMI). In our real-world clinical practice (N ¼ 116), thrombogenicity was evaluated with thromboelastography and conventional hemostatic measures, and CMD was defined as index of microcirculatory resistance of >40 U using the invasive physiologic test. High platelet- predicted the risk of atherothrombotic events in patients with acute coronary syndromes (4) (5) (6) (7) (8) . Restoration of perfusion triggers a cascade of events encompassing myocyte swelling, development of endothelial projections that occlude capillaries, platelet-neutrophil recruitment, and fibrin deposition (1) . In an experimental model, coronary microembolization by atherothrombotic debris has been shown to contribute to the occurrence of microvascular obstruction (9) . Because intrinsic hemostatic properties may affect the risk of microvascular obstruction (10) , proper assessment and pharmacologic modulation of these properties could be an effective therapeutic strategy to prevent the risk of CMD (11) (12) (13) (14) . Hemostasis is a complex process involving both cellular elements (eg, platelet function and inflammatory cells) and plasma proteins (inflammatory, procoagulant, anticoagulant, and fibrinolytic factors) (15 Table 1) . There were no differences in lesional and procedural characteristics between the groups. Patients with CMD showed lower CFR levels than those without CMD (1.5 AE 1.0 vs 2.0 AE 0.9; Table 2) . (Figures 5C and 5D ). This is the first study, to our knowledge, to suggest the influence of thrombogenicity on CMD occurrence and its prognostic implications in patients with AMI. The main findings of the study are as follows: 1) Values are n (%) or mean AE SD. ACC/AHA ¼ American College of Cardiology/American Heart Association; AMI ¼ acute myocardial infarction; BVS ¼ bioresorbable vascular scaffold; GFR ¼ glomerular filtration rate; HDL ¼ high-density lipoprotein; LDL ¼ low-density lipoprotein; MDRD ¼ modification of diet in renal disease; MI ¼ myocardial infarction; PCI ¼ percutaneous coronary intervention; SYNTAX ¼ Synergy Between PCI With Taxus and Cardiac Surgery; TIMI ¼ thrombolysis in myocardial infarction; WBC ¼ white blood cell. In the current analysis, a marked elevation in D-dimer levels was observed in patients with versus Values are mean AE SD. CFR ¼ coronary flow reserve; CMD ¼ coronary microvascular dysfunction; FFR ¼ fractional flow reserve; hs-CRP ¼ high-sensitivity C-reactive protein; IMR ¼ index of microcirculatory resistance; NT-proBNP ¼ N-terminal pro-B-type natriuretic peptide; PCI ¼ percutaneous coronary intervention; Pd ¼ distal coronary pressure; Tmn ¼ mean transit time; PRU ¼ P2Y12 reaction units. The TEG assay is a whole-blood ex vivo assay that measures the dynamic viscoelastic properties of clot generation from the time of initial plasmatic thrombin generation, to platelet-fibrin dependent clot formation, to clot strengthening, and finally to clot lysis (21) . The TEG assay also provides comprehensive information on thrombin generation, the interaction between fibrinogen/fibrin and platelets to form a platelet-fibrin clot, the contribution of Our study showed that post-PCI IMR of >40 U (the classic criterion of CMD) (4) was well correlated with pre-PCI P-FCS of $68 mm (16, 21, 29) , indicating a strong association between intrinsic hypercoagulability and CMD risk. Moreover, thrombogenic phenotype (ie, elevated P-FCS) significantly increased the risk of MACE only in AMI patients with CMD. In line with these observations, the combined assessment of CMD and P-FCS may enhance the prognosis assessment and assist in potential personalization of adjunctive therapeutic strategy in high-risk AMI patients (25) . High P-FCS may be a therapeutic target to determine the risks of CMD and long-term ischemic events (30 This is the first study to suggest a close relation of hypercoagulability (high P-FCS) assessed by TEG to CMD after reperfusion in AMI patients. In addition, the combined measurements of P-FCS and CMD may enhance the risk stratification and facilitate future targeting of adjunctive antithrombotic therapies. Invasive evaluation of the microvasculature in acute myocardial infarction: coronary flow reserve versus the index of microcirculatory resistance Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications Novel index for invasively assessing the coronary microcirculation Prognostic value of the index of microcirculatory resistance measured after primary percutaneous coronary intervention 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 Prognostic value of the index of microcirculatory resistance after percutaneous coronary intervention in patients with non-ST-segment elevation acute coronary syndrome Coronary microvascular dysfunction Coronary microvascular dysfunction Coronary microembolization No-reflow phenomenon after acute myocardial infarction is associated with reduced clot permeability and susceptibility to lysis. Arterioscler Thromb Vasc Biol Effect of intracoronary streptokinase administered immediately after primary percutaneous coronary intervention on long-term left ventricular infarct size, volumes, and function Effect of low-dose intracoronary alteplase during primary percutaneous coronary intervention on microvascular obstruction in patients with acute myocardial infarction: a randomized clinical trial Evaluation of microvascular injury in revascularized patients with ST-segmentelevation myocardial infarction treated with ticagrelor versus prasugrel Clinical utility of thromboelastography: one size does not fit all The Impact of platelet-fibrin clot strength on occurrence and clinical outcomes of peripheral artery disease in patients with significant coronary artery disease Fourth universal definition of myocardial infarction AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Heart Association Task Force on Practice Guidelines AHA/ACC key data elements and definitions for coronary revascularization: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Clinical Data Standards for Coronary Revascularization) Usefulness of the VerifyNow P2Y12 assay to evaluate the antiplatelet effects of ticagrelor and clopidogrel therapies Thrombin-induced platelet-fibrin clot strength: relation to high on-clopidogrel platelet reactivity, genotype, and post-percutaneous coronary intervention outcomes The potential use of the index of microcirculatory resistance to guide stratification of patients for adjunctive therapy in acute myocardial infarction Comparison of the effects of ticagrelor and clopidogrel on microvascular dysfunction in patients with acute coronary syndrome using invasive physiologic indices High thrombus burden in patients with COVID-19 presenting with ST-segment elevation myocardial infarction Viscoelastic properties of clot formation and their clinical impact in East Asian versus Caucasian patients with stable coronary artery disease: a COMPARE-RACE analysis Platelets in cardiac ischaemia/reperfusion injury: a promising therapeutic target Rivaroxaban with or without aspirin in stable cardiovascular disease Clinically significant bleeding with ticagrelor versus clopidogrel in Korean patients with acute coronary syndromes intended for invasive management: a randomized