[Usefulness of combination therapy of hybrid thrombolysis followed by back-up percutaneous transluminal coronary angioplasty in patients with acute myocardial infarction].

OBJECTIVES: Conventional thrombolytic therapy for acute myocardial infarction is effective for early reperfusion but has the disadvantage of a higher rate of bleeding complications. The purpose of this study is to elucidate efficacy and safety of a combined approach using a bolus injection of low dose of mutant tissue plasminogen activator (mt-PA) with heparin and aspirin to ensure definite antithrombin and antiplatelet efficacy, followed by back-up percutaneous transluminal coronary angioplasty(PTCA). METHODS: Patients with acute myocardial infarction aged < 80 years who were admitted to our institution within 3 hr of onset of symptoms were immediately treated with oral aspirin 330 mg and intravenous heparin 5,000 IU and were randomized to receive an intravenous bolus of mt-PA (monteplase) 15,000 IU/kg (thrombolytic group, n = 25) or no mt-PA (control group, n = 21), followed by angiography with PTCA if indicated. RESULTS: There were no differences between the two groups in patient characteristics, time from onset to hospital arrival, time to initial angiography, or infarct-related arteries. Significantly more patients had Thrombolysis in Myocardial Infarction flow grade 3 and grade 2/3 at the initial angiography in the thrombolytic group than in the control group (32.0% vs 4.8%, 68.0% vs 14.3%; p = 0.020, p = 0.0003, respectively). PTCA was performed in 88% of the thrombolytic group (stenting employed in 64%) and 95.5% of the control group (stenting in 57%), and the success rate was 95.5% and 100%, respectively. No acute or subacute coronary occlusion was found in either group. Bleeding complications occurred in only one patient in the thrombolytic group, which was bleeding associated with vomiting, and no difference was found in other complications between the two groups. Radionuclide ventriculography using quantitative gated single photon emission computed tomography showed left ventricular end-diastolic volume and left ventricular end-systolic volume tended to be smaller, and the ejection fraction after 3 months of treatment tended to be higher in the thrombolytic group. Myocardial salvage volume was significantly higher in the thrombolytic group. CONCLUSIONS: Hybrid thrombolysis using a low dose of mt-PA with aspirin and heparin promoted significantly early reperfusion. Also, successful reperfusion is achievable at higher rates with back-up PTCA without an increase in complications.

Relation of a common methylenetetrahydrofolate reductase mutation and plasma homocysteine with intimal hyperplasia after coronary stenting.

BACKGROUND: Hyperhomocysteinemia has been identified as an independent risk factor for coronary artery disease. Recent studies have shown that a common mutation (nucleotide 677 C-->T) in the methylenetetrahydrofolate reductase (MTHFR) gene may contribute to mild hyperhomocysteinemia and, therefore, to the incidence of coronary artery disease. No information exists, however, regarding the association between the mutation of the MTHFR gene or plasma homocysteine levels and morphological analysis of coronary atherosclerosis using intravascular ultrasound. METHODS AND RESULTS: To examine the potential influence of MTHFR genotype and homocysteine on coronaryarteries morphologically, we screened 62 patients with 65 lesions that were treated with 93 Palmaz-Schatz stents. The plasma homocysteine levels in the patients with the TT genotype were not significantly higher than those in the patients with non-TT (CC+CT) genotypes (13.1 +/- 5.5 versus 11.5 +/- 3.1 mmol/L, P=0.16). Angiographic analysis showed that the percent diameter stenosis in the patients with the TT genotype was significantly greater than that in those with non-TT genotypes (43.7 +/- 17.8% versus 29.0 +/- 22.0%, P=0.015). Intravascular ultrasound analysis showed that the TT genotype was significantly associated with greater intimal hyperplasia area (5.70 +/- 1.94 versus 3.72 +/- 1.38 mm2, P=0.001). In multiple stepwise regression analysis, the number of the T alleles was the only independent predictor of intimal hyperplasia after intervention (r2=0.21, P=0.004). CONCLUSIONS: The homozygous mutant genotype of the MTHFR gene may increase the risk of in-stent restenosis more than does the normal homozygous or heterozygous genotype.

Effect of quinapril on intimal hyperplasia after coronary stenting as assessed by intravascular ultrasound.

We studied whether angiotensin-converting enzyme inhibition with quinapril treatment can prevent in-stent restenosis after successful implantation of Palmaz-Schatz stents. Intravascular ultrasound study, but not quantitative coronary angiography analysis, revealed that quinapril treatment significantly prevented the loss of both minimal lumen cross-sectional area and lumen volume in stents, in addition to reducing the increase in intimal hyperplasia volume.