Impact of Insulin Resistance on Neointimal Tissue Proliferation after 2nd-Generation Drug-Eluting Stent Implantation.

Percutaneous coronary intervention is established as an effective treatment for patients with ischemic heart disease; in particular, drug-eluting stent implantation is known to suppress in-stent restenosis. Diabetes mellitus is an independent risk factor for restenosis, so reducing insulin resistance is being studied as a new treatment approach. In this prospective study, we sought to clarify the factors associated with in-stent restenosis after percutaneous coronary intervention, and we evaluated the homeostasis model assessment of insulin resistance (HOMA-IR) index as a predictor of restenosis. We enrolled 136 consecutive patients who underwent elective percutaneous coronary intervention at our hospital from February 2010 through April 2013. All were implanted with a 2nd-generation drug-eluting stent. We distributed the patients in accordance with their HOMA-IR index values into insulin-resistant Group P (HOMA-IR, ≥2.5; n=77) and noninsulin-resistant Group N (HOMA-IR, <2.5; n=59). Before and immediately after stenting, we measured reference diameter, minimal lumen diameter, and percentage of stenosis, and after 8 months we measured the last 2 factors and late lumen loss, all by means of quantitative coronary angiography. After 8 months, the mean minimal lumen diameter was smaller in Group P than that in Group N (1.85 ± 1.02 vs 2.37 ± 0.66 mm; P=0.037), and the mean late lumen loss was larger (0.4 ± 0.48 vs 0.16 ± 0.21 mm; P=0.025). These results suggest that insulin resistance affects neointimal tissue proliferation after 2nd-generation drug-eluting stent implantation.

Successful percutaneous coronary intervention of an anomalous right coronary artery with high anterior takeoff using a DIO thrombus aspiration catheter.

Selecting an appropriate guiding catheter is the most important determinant of procedural percutaneous coronary intervention success, especially with an anomalous right coronary artery with high anterior takeoff, which is rather complicated. We present a case of successful stent implantation in an anomalous right coronary artery with high anterior takeoff using DIO thrombus aspiration catheter. This method is useful when selection of the guiding catheter is rather complicated such as in the case of congenital coronary anomalies.

Circulating matrix metalloproteinase-1 and -3 in patients with an acute coronary syndrome.

To elucidate the diagnostic value of serum matrix metalloproteinase (MMP) levels, we measured MMP-1 and MMP-3 by a 1-step sandwich enzyme immunoassay. The transcardiac gradients of both MMPs were greater in patients with unstable angina and acute myocardial infarction than in patients with stable effort angina or control patients. Serum MMP levels appear to be a marker of plaque instability in patients with acute coronary syndrome.

Stent-induced expression and activation of the leukocyte integrin Mac-1 is associated with neointimal thickening and restenosis.

BACKGROUND: Increased expression of the beta2 integrin Mac-1 (CD11b/CD18, alphaMbeta2), which is responsible for firm leukocyte adhesion to platelets and fibrinogen at injured vessels, is found in association with neointimal hyperplasia after coronary interventions. The role of Mac-1 in the pathophysiology of restenosis is incompletely defined. To clarify further the role of Mac-1, we determined whether coronary stenting induced activation of Mac-1, which is required for high-affinity receptor-ligand interactions. METHODS AND RESULTS: Expression of CD11b (alpha-subunit of Mac-1) and binding of 8B2 (monoclonal antibody against an activation-dependent neoepitope of Mac-1) on the surface of polymorphonuclear leukocytes were analyzed in 62 patients undergoing coronary stenting using flow cytometric analysis of whole blood obtained from the coronary sinus and femoral vein. Transcardiac CD11b expression increased significantly at 24 hours and maximally at 48 hours after stenting; 8B2 began to increase at 10 minutes and was maximally increased at 48 hours after stenting. These changes were more prominent in patients with subsequent restenosis. Multiple regression analysis showed that the late lumen loss by quantitative coronary angiographic analysis was independently correlated with the CD11b increase (R=0.42, P<0.01) and the 8B2 increase (R=0.55, P<0.001) 48 hours after the procedure. Mac-1 activation, as assessed by 8B2 binding, was the most powerful predictor of late lumen loss. CONCLUSIONS: Coronary stenting produced upregulation and early activation of the leukocyte integrin Mac-1, which is associated with late lumen loss and restenosis. These data support a role for inflammation in neointimal thickening and suggest the validity of targeting leukocyte recruitment for preventing clinical restenosis.

Accelerated plasminogen activator inhibitor may prevent late restenosis after coronary stenting in acute myocardial infarction.

BACKGROUND: Although acceleration of plasma plasminogen activator inhibitor-1 (PA-1) level after emergent coronary angioplasty in acute myocardial infarction (AMI) has been documented, its pathophysiologic role is still unknown. HYPOTHESIS: This study was designed to elucidate the role of PAI-1 in the development of restenosis after primary coronary stenting in AMI. METHODS: We selected for this study 66 patients with AMI, who underwent primary coronary stenting for infarct-related coronary artery lesions in an emergent situation. In all patients, plasma PAI-1 level was measured at admission, and at 3 h, 24 h, 48 h, and 1 month after coronary stenting. RESULTS: At admission, the PAI-1 level was equivalent in 24 patients who experienced restenosis and in 42 patients without restenosis (28 +/- 4 vs. 29 +/- 4 ng/ml). In patients with restenosis, the levels did not change during the course after coronary stenting. In patients without restenosis, however, the level significantly increased at 3 h (48 +/- 9 ng/ml, p < 0.001), 24 h (42 +/- 9, p < 0.01), and 48 h (38 +/- 7, p < 0.05) after coronary stenting, and was restored to the level equivalent to that at admission (27 +/- 2 ng/ml) I month aftercoronary stenting. The PA-1 level at 3 h after coronary stenting in patients without restenosis was significantly higher (p < 0.05) than the level (33 +/- 6 ng/ml) in patients with restenosis. Multiple logistic regression analysis indicated that the PAI-1 level 3 h after coronary stenting was an independent predictor of restenosis (Wald chi2 = 3.826, p = 0.019, odds ratio 0.921, 95% confidence interval 0.866-0.961). CONCLUSION: Accelerated PAI-1 after coronary stenting in patients with AMI may protect against the development of late restenosis.

Clinical significance of the antibody against oxidized low-density lipoprotein in acute myocardial infarction.

To establish the clinical significance of the antibody against oxidized low-density lipoprotein (anti-Ox-LDL) titer in patients with acute myocardial infarction (AMI), we measured the anti-Ox-LDL titer in 39 patients with AMI and 25 controls. In all AMI patients, the anti-Ox-LDL titer on admission was higher (p < 0.05) than the value in the controls. One month after admission, the titer decreased significantly (p < 0.001) reaching control levels. In patients who underwent thrombolytic therapy, the anti-Ox-LDL titer on admission was identical in patients with occluded infarct-related arteries (IRA) and patients with patent IRA during emergency coronary angiography. In patients who did not undergo thrombolytic therapy, the anti-Ox-LDL titer on admission was higher in patients with occluded IRA than in patients with patent IRA. An increased anti-Ox-LDL titer may be a risk factor for the onset of AMI. Spontaneous recanalization of the IRA may be associated with increased anti-Ox-LDL titers, while thrombolysis-induced recanalization may be independent of it.

A new thrombolytic agent, monteplase, is independent of the plasminogen activator inhibitor in patients with acute myocardial infarction: initial results of the COmbining Monteplase with Angioplasty (COMA) trial.

BACKGROUND: Both thrombolytic therapy and coronary angioplasty have been inconsistent together for primary acute myocardial infarction (AMI) therapy, because conventional thrombolytic agents accelerate plasminogen activator inhibitor-1 (PAI-1) activity. However, combining newly developed mutant tissue-type plasminogen activators with coronary angioplasty should be reconsidered. METHODS: This study was designed to investigate clinical usefulness of such an agent, monteplase, for treatment of AMI in light of PAI-1 kinetics. One hundred fifty-four consecutive patients with AMI were randomly assigned to receive direct coronary angioplasty (Group I) or coronary angioplasty after pretreatment with intravenous monteplase (Group II). In 90 of these patients, total PAI-1 antigen levels were serially measured. RESULTS: Baseline PAI-1 levels at admission were higher in patients with occluded infarct-related arteries than in patients with patent arteries in Group I (39 +/- 4 vs 20 +/- 2 ng/mL, P <.01) and in Group II (36 +/- 3 vs 27 +/- 2 ng/mL, P <.05). In the high PAI-1 level subgroup (> or =27 ng/mL, n = 53), Group II showed a higher patency rate than Group I (56 vs 18%, P <.01). Multiple logistic regression analysis indicated that patency could be predicted by the PAI-1 level in Group I (Wald chi2= 3.94, P =.02, odds ratio 0.924, 95% CI 0.855-0.999), but not in Group II. Serial change patterns in the PAI-1 level were identical in Group I and Group II. CONCLUSION: Because monteplase can be used independently of PAI-1 kinetics, a combination of monteplase administration at a community hospital with prompt transfer to a tertiary center for coronary intervention may be a powerful strategy for AMI.

Early recanalization and plasma brain natriuretic peptide as an indicator of left ventricular function after acute myocardial infarction.

BACKGROUND: Although plasma brain natriuretic peptide (BNP) levels have been widely measured in patients with acute myocardial infarction (AMI), it is still uncertain whether the early recanalization modulates the levels and whether the levels can predict chronic stage left ventricular function. This study was designed to elucidate these issues. METHODS: In 80 consecutive patients with AMI, plasma BNP levels were measured at admission and at 4 hours, 24 hours, 48 hours, and 1 month after admission. RESULTS: In 35 of the 80 patients, the infarct-related artery was patent within 6 hours from the onset of MI (6-hour patency group), and in 27 patients, the artery was still occluded after 6 hours (6-hour occlusion group). The remaining 18 patients in whom it was unclear whether recanalization of the infarct-related artery had occurred within 6 hours or not were excluded from the analyses. In the 6-hour patency group, the BNP level gradually increased and reached a maximum value at 24 hours after admission. In the 6-hour occlusion group, the level increased more, with the values at 4 hours, 24 hours, and 48 hours significantly higher than those in the 6-hour patency group (86 +/- 18 pmol/L versus 35 +/- 8 pmol/L; P <.01; 112 +/- 13 pmol/L versus 74 +/- 9 pmol/L; P <.05; 102 +/- 15 pmol/L versus 53 +/- 11 pmol/L; P <.01). Chronic stage left ventricular function was correlated with not only the BNP level at same stage but also that at 24 hours and that at 48 hours after admission. Multiple regression analysis indicated that the BNP level at 24 hours was the most powerful predictor of chronic stage left ventricular function. CONCLUSION: Plasma BNP levels can predict subsequent cardiac function. In addition, the importance of early recanalization may also be supported with BNP kinetics.

A case of double-chambered right ventricle associated with an interventricular septal aneurysm in an elderly patient.

Double-chambered right ventricle is a congential malformation caused by an anomalous muscle band obstructing the right ventricular outflow tract. Most reported cases of this condition have been diagnosed in infants, or adolescents. We encountered a 61-year-old woman with a double-chambered right ventricle, associated with a large interventricular septal aneurysm, which is a rare complication. The right ventricular obstruction was corrected with surgery.