Yo Iwata

Effect of balloon inflation time on expansion of sirolimus-eluting stent

There is little information about the relationship between balloon inflation time and sirolimus-eluting stent (SES) expansion. In this randomized intravascular ultrasound (IVUS) study, 92 de novo lesions in native coronary arteries that underwent SES implantation were enrolled. Sirolimus-eluting stent was implanted using an inflation pressure of 14 atm. Stent balloon was gradually inflated until 14 atm in 10 s. In the short inflation group, it was deflated immediately after an image of the balloon inflated at 14 atm was taken. Stent balloon inflation lasted 60 s in the long inflation group. Intravascular ultrasound was then performed. The long balloon inflation resulted in a larger stent cross-sectional area (4.9 ± 1.6 mm2 vs 4.3 ± 1.4 mm2, P < 0.05) and expansion (71% ± 13% vs 60% ± 13%, P < 0.001) compared to the short balloon inflation, although stent expansion was relatively low in both groups. The relatively longer balloon inflation time using an inflation pressure of 14 atm results in better SES expansion. However, in the majority of lesions, adequate stent expansion is not achieved even using long balloon inflation, if it is inflated at 14 atm.

Effect of pioglitazone on endothelial dysfunction after sirolimus-eluting stent implantation.

Previous studies have demonstrated endothelial dysfunction after sirolimus-eluting stent (SES) implantation. The present study evaluated the effect of pioglitazone on endothelial dysfunction after SES implantation in nondiabetic patients. A total of 50 nondiabetic patients who had undergone SES implantation were randomly assigned to the pioglitazone group (n = 25) or the control group (n = 25). Endothelial function was estimated by measuring the coronary vasoreactivity in the reference segment within 15 mm proximal and distal to the SES in response to intracoronary acetylcholine infusion (10(-8) and 10(-7) mol/L) at 9 months of follow-up. Endothelium-independent vasomotion was assessed after an intracoronary bolus of nitroglycerin. Changes in the coronary diameter in response to 10(-8) and 10(-7) mol/L acetylcholine in the segment proximal to the SES were not significantly different between the pioglitazone and control groups. In contrast, in the segment distal to the SES, vasoconstrictions to 10(-8) (-3.0 ± 2.8% vs -7.1 ± 4.5%, p <0.01) and 10(-7) mol/L acetylcholine (-6.2 ± 8.0% vs -13.1 ± 8.9%, p <0.01) were attenuated in the pioglitazone group compared to the control group. Endothelium-independent vasodilation to nitrate did not differ between the 2 groups. Multivariate analysis showed that pioglitazone was an independent predictor improving endothelial dysfunction after SES implantation. In conclusion, pioglitazone might improve endothelial dysfunction after SES implantation in nondiabetic patients.

Coronary artery endothelial dysfunction associated with sleep apnea.

There is little information about coronary artery endothelial dysfunction in patients with sleep apnea. We evaluated relation between severity of sleep apnea and coronary artery endothelial dysfunction. In all, 26 patients without significant coronary stenoses were enrolled. Endothelial function was estimated by measuring coronary vasoreactivity in response to acetylcholine infusion (10-7 mol/L) into coronary arteries. Vasoconstriction rate was defined as ([lumen diameter after isosorbide dinitrate injection - lumen diameter after acetylcholine injection]/lumen diameter after isosorbide dinitrate injection × 100). Vasoconstriction rate was calculated at each major coronary artery and the highest value was used for that patient. Overnight sleep study was performed and the apnea-hypopnea index (AHI) was calculated as the mean number of apneas and hypopneas per hour of sleep. There was significant correlation between AHI and vasoconstriction rate (P = .04). There is significant correlation between severity of sleep apnea and endothelial function of coronary arteries.

Ubiquitous atherosclerosis in coronary arteries without angiographically significant stenosis

Previous intravascular ultrasound (IVUS) studies have shown coronary artery atherosclerosis even in angiographically normal reference segment. However, IVUS has not been performed in all of the three major coronary arteries. A total of 50 patients with single-vessel disease underwent IVUS evaluation in the proximal two-thirds of the three major coronary arteries. Lumen and external elastic membrane cross-sectional areas were measured at 1-mm intervals. To compensate the difference in pullback length among coronary arteries, normalized total plaque and media volume (TPV) was calculated as TPV/number of slices in pullback × median number of slices in study population. Percent plaque and media volume (PPV) was calculated as TPV/Σ external elastic membrane cross-sectional area × 100. A cross section was defined as atherosclerotic if maximum intimal thickness exceeded 0.5 mm at any point in the vessel circumference. There was no significant difference in normalized TPV, PPV, and the incidence of abnormal intimal thickness between coronary arteries with and without significant stenosis. Frequency distribution of plaque burden was similar. Atherosclerosis is ubiquitous even in coronary arteries without angiographically significant stenosis. The extent of atherosclerosis is similar between coronary arteries with and without significant stenosis.

Effects of stem cell mobilization by granulocyte colony-stimulating factor on endothelial function after sirolimus-eluting stent implantation: A double-blind, randomized, placebo-controlled clinical trial

BACKGROUND Stem cell mobilization by granulocyte colony-stimulating factor (G-CSF) has been shown to enhance endothelial healing after spontaneous or iatrogenic arterial disruption. Granulocyte colony-stimulating factor treatment might attenuate endothelial dysfunction after sirolimus-eluting stent (SES) implantation that may be associated with adverse cardiac events during follow-up. This prospective, double-blind, randomized, placebo-controlled study investigated whether G-CSF improved endothelial dysfunction after SES implantation. METHODS One hundred patients who underwent SES implantation were randomly assigned to the G-CSF (n = 50) or the placebo group (n = 50). They received daily subcutaneous injection of 300 μg G-CSF or saline for 5 days. Endothelial function was estimated by measuring the coronary vasoreactivity in the segments 15 mm proximal and distal to SES in response to intracoronary infusion of acetylcholine (10(-8) and 10(-7) mol/L) at 9-month follow-up. RESULTS Follow-up angiography was performed in 41 G-CSF patients (82%) and 46 placebo patients (92%) (P = .14). Changes in coronary diameter in response to acetylcholine infusion in the proximal segment were not significantly different between the 2 groups. However, vasoconstriction in the distal segment in response to 10(-8) mol/L (-3.9% ± 6.4% vs -7.0% ± 8.1%, P < .05) and 10(-7) mol/L (-8.8% ± 11.0% vs -15.2% ± 7.6%, P < .01) acetylcholine infusion was attenuated in the G-CSF group. Endothelium-independent vasodilatation after nitrate infusion did not differ between the 2 groups. CONCLUSION Granulocyte colony-stimulating factor attenuates endothelial dysfunction after SES implantation.

Antiplatelet effect of 50-mg maintenance dose of clopidogrel compared to 200 mg ticlopidine: a preliminary study

In the United States and Europe, patients with coronary stents are maintained on 75 mg clopidogrel. Because the maintenance dose of ticlopidine in patients with coronary stents is 100 mg twice daily in Japan and 250 mg twice daily in the United States and Europe, in Japanese patients a lower dose of clopidogrel may achieve an antiplatelet effect comparable to 200 mg ticlopidine. Platelet aggregation was evaluated in 104 consecutive patients on 50 mg clopidogrel plus aspirin (n = 54) and 200 mg ticlopidine plus aspirin (n = 50). Platelets were stimulated with adenosine diphosphate (5 and 20 μmol/l) and aggregation was assessed by optical aggregometry. There was no significant difference in platelet aggregation induced with 5 (37% ± 11% vs 38% ± 15%, not significant) and 20 μmol/l adenosine diphosphate (48% ± 13% vs 51% ± 12%, not significant) between 50 mg clopidogrel and 200 mg ticlopidine. In Japanese patients, there is the possibility that a maintenance dose of 50 mg clopidogrel on platelet inhibition is comparable to 200 mg ticlopidine.

Identification of Cerebral Infarction-Specific Antibody Markers from Autoantibodies Detected in Patients with Systemic Lupus Erythematosus

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease which may be caused by development of the autoantibodies. On the other hand, SLE is a high-risk group of atherosclerosis, so it is possible that some of autoantibodies in SLE are the result of atherosclerosis-related diseases such as cerebral infarction (CI), cardiovascular disease (CVD) and diabetes mellitus (DM). Methods: The initial screening of autoantibodies was performed using the protein array method. AlphaLISA was used to analyze the serum antibody levels using synthetic polypeptides as antigens. Results: After the initial screening using protein array, we identified 67 antigens that were recognized by IgG antibodies in sera of patients with SLE. In the second screening, 170 peptides derived from amino acid sequences of 67 antigens were synthesized and used as antigens for analysis of serum antibody levels by AlphaLISA. The antibody levels for ten peptides were significantly higher in the sera of patients with SLE than in those of healthy donors. Further AlphaLISA analysis of sera of patients with CI, CVD or DM revealed that the serum antibody levels for four peptides derived from SOSTDC1, CTNND1, CLDND1 and CCNG2 were elevated in patients as compared to those of healthy donors. Conclusions: Serum antibody levels against peptide antigens of SOSTDC1, CTNND1, CLDND1 and CCNG2 are useful markers for diagnosis of the progression of CI, CVD and/or DM.

Efficacy and safety of low-dose clopidogrel in Japanese patients after drug-eluting stent implantation: a randomized pilot trial

In Japan, a lower maintenance dose of ticlopidine is used than in the United States and Europe. Therefore a lower maintenance dose of clopidogrel may also be considered appropriate in Japanese patients. The present randomized pilot study evaluated the efficacy and safety of 50 mg clopidogrel in Japanese patients who underwent drug-eluting stent (DES) implantation. A total of 200 patients with 277 lesions who underwent intravascular ultrasound-guided DES implantation were enrolled. The subjects were allocated to the 50- or 75-mg clopidogrel group. All patients received 100 mg aspirin daily before the procedure, and this continued indefinitely. The duration of clinical follow-up was 21.8 ± 5.7 months in the 75-mg group and 21.9 ± 6.1 months in the 50-mg group (P = 0.96). During follow-up, no cardiac death, myocardial infarction, or stent thrombosis was observed in either group. Side effects of clopidogrel were observed in 4 patients (4.0 %) in the 75-mg group and in 4 patients (4.0 %) in the 50-mg group. Following this randomized pilot study, it may be justified to perform a large-scale randomized study comparing 50- and 75-mg dosing of clopidogrel in Japanese patients undergoing coronary stent implantation.

Recovery of endothelial function after sirolimus-eluting stent implantation: a pilot study.

Whether endothelial dysfunction after sirolimus-eluting stent (SES) implantation is persistent has not been fully evaluated. Endothelial function was evaluated in 152 lesions that underwent follow-up coronary angiography after SES implantation. Lesions were classified into 2 groups according to the duration between SES implantation and follow-up: ≤12 months (n = 95) and >12 months (n = 57). Changes in coronary diameter in response to 10−8 mol/L (−2.4% ± 6.3% vs −4.9% ± 3.8%, P < .01) and 10−7 mol/L acetylcholine (Ach; −4.6% ± 7.6% vs −10.7% ± 9.1%, P < .001) in segment proximal to SES were significantly attenuated in the >12-month group than in the ≤12-month group. There were less changes in coronary diameter in response to 10−8 mol/L (−2.3% ± 4.6% vs −6.9% ± 5.0%, P < .001) and 10−7 mol/L Ach (−6.5% ± 11.4% vs −16.8% ± 10.5%, P < .001) in segment distal to SES in the >12-month group. Endothelial dysfunction may diminish long after SES implantation.

Genetic and non-genetic factors responsible for antiplatelet effects of clopidogrel in Japanese patients undergoing coronary stent implantation: An algorithm to predict on-clopidogrel platelet reactivity

INTRODUCTION Antiplatelet effects of clopidogrel appear to be affected by various factors including genetic polymorphism. So far, there has been little information about the response of clopidogrel in Asians, whose prevalence of a CYP2C19 loss-of-function (LOF) allele is high. METHODS AND RESULTS We investigated background and clinical factors affecting on-clopidogrel platelet reactivity in Japanese patients undergoing coronary stent implantation (n=114). In univariate analysis, antiplatelet effects of clopidogrel in a steady state were associated with not only CYP2C19 genotypes but also several factors including dyslipidemia. In addition, we developed an algorithm that can estimate P2Y12 Reaction Units (PRU) in a steady state by multiple regression analysis and evaluated the adequacy of the algorithm by the Akaike Information Criterion. CONCLUSIONS We revealed several factors influencing on-clopidogrel platelet reactivity in Japanese patients. We also succeeded in developing an algorithm that estimates PRU in a steady state, although it is uncertain whether the algorithm can be applied to other populations.