Abstract
Background: In most cases, sudden cardiac death is triggered by ischemia‐related ventricular tachyarrhythmias and accounts for 50% of deaths from cardiovascular disease in developed countries. Chronic elevation of indicators of coagulation activation has been found in patients with coronary heart disease, but a role of coagulation activation as a potential risk factor for ventricular fibrillation (VF) during acute myocardial infarction (MI) has not been investigated.
Methods: We enrolled 50 patients with a history of MI, of whom 26 presented with VF in the acute phase of myocardial ischemia; 24 patients had an acute MI without ventricular tachyarrhythmias. Levels of thrombin‐antithrombin complexes (TAT), prothrombin fragment F1 + 2 (F1 + 2), fibrinopeptide A (FPA), plasmin‐antiplasmin complexes (PAP), protein C, antithrombin, activated partial thromboplastin time (aPTT), thromboplastin time, D‐Dimer, fibrinogen, and high‐sensitivity C‐reactive protein (hs‐CRP) were measured in plasma samples of all patients. Blood collection was obtained sequentially in two separate settings. Patients were studied at a median of 3 51 days after the acute coronary event.
Results: Higher levels of TAT complexes (13.4 ± 22.2 vs. 3.03 ± 4.3 μg/1; p = 0.02), FPA (79.7 ± 132.3 vs. 24.04±41.3 ng/ml; p = 0.04), and F1+2 (1.89 ± 1.3 vs. 1.16 ± 0.5 nmol/l; p = 0.01) were observed in patients with VF compared with patients without ventricular tachyarrhythmias during the acute phase of MI. D‐Dimer levels displayed a trend without reaching statistical significance (0.69 ± 0.48 vs. 0.48 ± 0.24 mg/l; p = 0.06). No differences were found in hs‐CRP (3.25 ± 4.5 vs. 4.4 ± 8.8 mg/l; p = 0.5) and fibrinogen (2.8 ± 0.9 vs. 2.7 ± 0.9 g/l; p = 0.6) measurements. Repeat assessment of markers of coagulation activation atamedian of 847 days revealed a highly significant decrease in patients with VF.
Conclusions: Markers of thrombin generation are transiently increased in patients with VF during the acute phase of MI. These findings have implications for risk assessment and genetic screening of patients prone to VF during acute myocardial ischemia.
Keywords: acute myocardial infarction, ventricular fibrillation, coagulation
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References
- 1. Huikuri HV, Castellanos A, Myerburg RJ: Sudden death due to cardiac arrhythmias. N Engl J Med 2001; 345: 1473–1482 [DOI] [PubMed] [Google Scholar]
- 2. Spooner PM, Albert C, Benjamin EJ, Boineau R, Elston RC, George AL Jr, Jouven X, Kuller LH, MacCluer JW, Marban E, Muller JE, Schwartz PJ, Siscovick DS, Tracy RP, Zareba W, Zipes DP: Sudden cardiac death, genes, andarrhythmogenesis. Circulation 2001; 103: 2447–2452 [DOI] [PubMed] [Google Scholar]
- 3. Myerburg RJ: Scientific gaps in the prediction and prevention of sudden cardiac death. J Cardiovasc Electrophysiol 2002; 13: 709–723 [DOI] [PubMed] [Google Scholar]
- 4. Goldstein JA, Butterfield MC, Ohnishi Y, Shelton TJ, Corr PB: Coronary heart disease/myocardial infarction: Arrhythmogenic influence of intracoronary thrombosis during acute myocardial infarction. Circulation 1994; 90 (1): 139–147 [DOI] [PubMed] [Google Scholar]
- 5. Coronel R, Wilms‐Schopman FJG, Janse MJ: Profibrillatory effects of intracoronary thrombus in acute regional ischemia of the in situ porcine heart. Circulation 1997; 96 (11): 3985–3991 [DOI] [PubMed] [Google Scholar]
- 6. Markwardt F, Franke T, Glusa E, Nilius B: Pharmacological modification of mechanical and electrical responses of frog heart to thrombin. Arch Pharmacol 1990; 341: 341–346 [DOI] [PubMed] [Google Scholar]
- 7. Abdelkarim S, Galina M, Hong Lu Z, Pak E, Darrow A, Andrade‐Gordon P, Steinberg SF: Signaling properties and functions of two distinct cardiomyocyte protease‐activatedreceptors. Circ Res 2000; 86 (10): 1054–1061 [DOI] [PubMed] [Google Scholar]
- 8. Park TH, McHowat J, Wolf RA, Corr PB: Increased lysophosphatidylcholine content induced by thrombin receptor stimulation in adult rabbit cardiac ventricular myocytes. Cardiovasc Res 1994; 28: 1263–1268 [DOI] [PubMed] [Google Scholar]
- 9. Pinet C, Le Grand B, John G, Coulumbe A: Thrombin facilitation of voltage‐gated sodium channel activation in human cardiomyocytes. Circulation 2002; 106: 2098–2103 [DOI] [PubMed] [Google Scholar]
- 10. Menown IB, Mathew TP, Gracey HM, Nesbitt GS, Murray P, Young IS, Adgey AA: Prediction of recurrent events by D‐Dimer and inflammatory markers in patients with normal cardiac troponin I (PREDICT) study. Am Heart J 2003; 145: 986–992 [DOI] [PubMed] [Google Scholar]
- 11. Harb TS, Zareba W, Moss AJ, Ridker PM, Rifai N, Marder VJ, Miller‐Watelet L, and the THROMBO Investigators : Association between inflammatory markers, hemostatic, and lipid factors in postinfarction patients. Am J Cardiol 2003; 91 (9): 1120–1123 [DOI] [PubMed] [Google Scholar]
- 12. Albert CM, Ma J, Rifai N, Stampfer MJ, Ridker PM: Prospective study of C‐reactive protein, homocysteine, and plasma lipid levels as predictors of sudden cardiac death. Circulation 2002; 105: 2595–2599 [DOI] [PubMed] [Google Scholar]
- 13. Janse MJ, Wit AL: Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. Physiol Rev 1989; 69: 1049–1149 [DOI] [PubMed] [Google Scholar]
- 14. Burke AP, Farb A, Malcom GT, Liang YH, Smialek J, Virmani R: Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med 1997; 336: 1276–1282 [DOI] [PubMed] [Google Scholar]
- 15. Creer MH, Dobmeyer DJ, Corr PB: Amphipathic lipid metabolites and arrhythmias during myocardial ischemia In Cardiac Electrophysiology: From Cell to Bedside, 2nd ed. (Eds. Zipes DP, Jalife J.). Philadelphia, Pa.: WB Saunders, 1995. [Google Scholar]
- 16. Yasutake M, Haworth RS, King A, Avkiran M: Thrombin activates the sarcolemmal Na+‐H+ exchanger: Evidence for a receptor‐mediated mechanism involving protein kinase C. Circ Res 1996; 79: 705–715 [DOI] [PubMed] [Google Scholar]