Benefit of Thrombolytic Therapy Is Sustained Throughout Five Years and Is Related to TIMI Perfusion Grade 3 But Not Grade 2 Flow at Discharge

Lenderink, Timo; Simoons, Maarten L.; Es, Gerrit‐Anne van; Werf, Frans Van de; Verstraete, Marc; Arnold, Alfred

doi:10.1161/01.cir.92.5.1110

Cited by 114 publications

(44 citation statements)

References 19 publications

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“…TIMI-3 flow at initial angiography has been shown to be a strong predictor of mortality in trials of fibrinolytic therapy (4,31,32) and trials of primary PCI (33)(34)(35). However, improved TIMI-3 flow at initial angiography was not clinically correlated with improved outcomes in trials of facilitated PCI.…”

Section: Discussion Timi-3 Flow At Initial Angiography and Observed Omentioning

confidence: 99%

Systematic review of fibrinolytic-facilitated percutaneous coronary intervention: Potential benefits and future challenges

Afilalo

Roy

Eisenberg

2009

Canadian Journal of Cardiology

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P rimary percutaneous coronary intervention (PCI) has been shown to be superior to fibrinolytic therapy for the treatment of ST segment elevation myocardial infarction (STEMI) (1). However, primary PCI is suboptimal when there are prolonged delays for interhospital transfer or resource mobilization. Facilitated PCI is defined as the administration of fibrinolytic therapy and/or glycoprotein (GP) IIb/IIIa inhibitors while waiting for PCI. The rationale is to open infarctrelated arteries (IRAs) as soon as possible, minimize myocardial ischemia time and, thus, salvage at-risk myocardium. Despite the theoretical benefits, randomized controlled trials have failed to support the clinical benefits of this strategy. These trials varied substantially in terms of facilitating regimens, timing of fibrinolysis, timing of PCI, and coadministered antiplatelet or antithrombin therapies. A recent metaanalysis (2) showed that facilitated PCI was associated with increased short-term mortality, reinfarction, major bleeding and stroke. Although the results of this meta-analysis were unequivocally negative, a systematic review may be better suited to address these heterogeneous and complex trials. Our objective was to systematically review trials of fibrinolytic-facilitated versus nonfacilitated PCI, and determine when this strategy may be beneficial and deserving of further research. BACKGROUND: Facilitated percutaneous coronary intervention (PCI) is defined as the administration of fibrinolytic therapy and/or glycoprotein (GP) IIb/IIIa inhibitors to minimize myocardial ischemia time while waiting for PCI. A pooled meta-analysis suggested that facilitated PCI was associated with higher rates of mortality and morbidity compared with nonfacilitated PCI. OBJECTIVE: The heterogeneous and complex trials of facilitated PCI were systematically reviewed to identify where this strategy may be beneficial and deserving of further research. METHODS: MEDLINE, EMBASE, the Cochrane database, the Internet and conference proceedings were searched to obtain relevant trials. Human studies that randomly assigned patients to fibrinolytic-facilitated PCI (administration of fibrinolytic therapy alone or in combination with GP IIb/IIIa inhibitors before angiography) versus nonfacilitated PCI were included. RESULTS: Nine trials encompassing 3836 patients were reviewed. The facilitated PCI strategy was fibrinolytic therapy alone in seven trials and half-dose fibrinolytic therapy plus GP IIb/IIIa inhibitors in two trials. In patients who had fibrinolysis less than 2 h after symptom onset (mainly in the prehospital setting) and/or slightly delayed PCI 3 h to 24 h after fibrinolysis, facilitated PCI was associated with the greatest Thrombolysis In Myocardial Infarction (TIMI) grade 3 flow and a trend toward reduced mortality. Overall, facilitated PCI was associated with increased intracranial hemorrhage and reinfarction. Combining half-dose fibrinolytic therapy and GP IIb/IIIa inhibitors reduced reinfarction but increased major bleeding. CONCLUSIONS: Facilitat...

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Section: Discussion Timi-3 Flow At Initial Angiography and Observed Omentioning

confidence: 99%

Systematic review of fibrinolytic-facilitated percutaneous coronary intervention: Potential benefits and future challenges

Afilalo

Roy

Eisenberg

2009

Canadian Journal of Cardiology

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“…11 We hypothesized that impairment of the arterial baroreflex is a major determinant of the poor prognosis of patients with incomplete reperfusion. The major finding of the present study is that successful early restoration of antegrade flow by means of mechanical reopening of the infarct-related coronary artery is associated with an immediate significant recovery in the baroreflex.…”

Section: Discussionmentioning

confidence: 99%

Reflex Cardiac Activity in Ischemia and Reperfusion

et al. 2003

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Background-Abnormal heart rate turbulence (HRT) is associated with an increased risk of mortality in the chronic phase of myocardial infarction (MI) in the prethrombolytic and thrombolytic eras. However, the impact of direct percutaneous coronary intervention (PCI) on HRT in the acute phase of MI and its association to the epicardial infarct-related arterial flow has not been examined. Methods and Results-We investigated HRT in 126 patients undergoing direct PCI for a first MI. Turbulence onset and turbulence slope were determined before reperfusion, during the initial 2 hours after reperfusion, and during hours 6 to 24 after reperfusion. HRT significantly improved after PCI. There were no significant differences in baseline clinical characteristics between Thrombolysis in Myocardial Infarction Trial classification (TIMI) 2 (nϭ28) and TIMI 3 (nϭ98) flow. After PCI, turbulence slope increased (13.2Ϯ11 to 18.1Ϯ12 ms/beat, PϽ0.001) and turbulence onset decreased (Ϫ0.008Ϯ0.04% to Ϫ0.023Ϯ0.04%, PϽ0.01) in patients with TIMI 3 flow after PCI, whereas there were no significant alterations of turbulence slope (12.2Ϯ10 to 12.8Ϯ6.5 ms/beat) and turbulence onset (Ϫ0.009Ϯ0.05% to Ϫ0.003Ϯ0.03%) in patients with TIMI 2 flow. Conclusions-The

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“…1 Indeed, prognosis directly correlates with viable tissue mass after infarct. 2 In mammals, cardiomyocytes start to exit the cell cycle midway through gestation, and effectively cease proliferating within the neonatal period. 3 In rats aged 1-5 days, the percent of ventricular cardiomyocytes undergoing DNA synthesis ranges between 2 and 15% according to diverse reports, however, this number decreases to p1% by 21 days.…”

Section: Introductionmentioning

confidence: 99%

Adenoviral delivery of human CDC5 promotes G2/M progression and cell division in neonatal ventricular cardiomyocytes

et al. 2006

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Heart failure results from the cumulative death of cardiomyocytes, and the inability of remaining cells to regenerate. Efforts toward transcriptional reprogramming of cardiomyocytes by overexpressing E1A or E2F1 have been limited by the inability of cardiomyocytes to enter and complete mitosis. Human CDC5 (hCDC5), a component of the pre-mRNA splicing complex, has been shown to regulate G2/M transit in asynchronously dividing cells. We now show that co-infection of recombinant adenoviruses expressing E1A/E1B and hCDC5 promotes cell cycle re-entry and G2/M progression in post-mitotic cardiomyocytes. Co-expression of E1A/E1B and hCDC5 induced nuclear localization of cyclin-dependent kinase 1 and cyclin B1, and was sufficient to promote mitotic entry as determined by an increase in mitotic index only in co-infected cells. E1A/E1B and hCDC5 promoted cell division, as evidenced by an increase in the number of cardiomyocytes following co-infection. Thus, overexpression of E1A/E1B and hCDC5 resulted in cell cycle re-entry, DNA synthesis, cell division, and an increase in cardiomyocyte number, suggesting the formation of new cardiomyocytes. These studies suggest that G1/S-phase transcriptional regulators, in combination with pre-mRNA splicing factors, such as CDC5, that regulate rate-limiting G2/M target genes may prove useful in developing therapies to stimulate myocardial regeneration. Gene Therapy (2006) 13, 837-843.

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Benefit of Thrombolytic Therapy Is Sustained Throughout Five Years and Is Related to TIMI Perfusion Grade 3 But Not Grade 2 Flow at Discharge

Cited by 114 publications

References 19 publications

Systematic review of fibrinolytic-facilitated percutaneous coronary intervention: Potential benefits and future challenges

Systematic review of fibrinolytic-facilitated percutaneous coronary intervention: Potential benefits and future challenges

Reflex Cardiac Activity in Ischemia and Reperfusion

Adenoviral delivery of human CDC5 promotes G2/M progression and cell division in neonatal ventricular cardiomyocytes

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