北原 秀喜

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.

Usefulness of higher (>300 mg) loading doses of clopidogrel has been demonstrated in studies from the United States and Europe. The present study evaluated platelet aggregation after the administration of a 450-mg loading dose of clopidogrel in Japanese patients undergoing coronary stenting. Platelet aggregation was serially measured at baseline, and 2, 4, 6, and 8 h after 450-mg clopidogrel loading in 25 patients undergoing coronary stenting. Platelets were stimulated with 5 and 20 micromol/l adenosine diphosphate (ADP) and aggregation was assessed by optical aggregometry. Platelet aggregation (5 micromol/l ADP 42.8% +/- 13.5% and 20 micromol/l ADP 51.2% +/- 11.6%) was significantly suppressed <or=4 h after 450-mg clopidogrel loading. There were no adverse events except one minor nasal bleed. The present study shows that platelet inhibition is achieved <or=4 h after the administration of a 450-mg clopidogrel loading dose in Japanese patients.

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 x median number of slices in study population. Percent plaque and media volume (PPV) was calculated as TPV/Sigma external elastic membrane cross-sectional area x 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.

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 mumol/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 mumol/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.

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 mm(2) vs 4.3 +/- 1.4 mm(2), 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.

BACKGROUND: There is limited information about optimal management of drug-eluting stent (DES) restenosis. This study evaluated the incidences of re-restenosis and re-target lesion revascularization (TLR) after the treatment of sirolimus-eluting stent (SES) restenosis. METHODS AND RESULTS: A total of 102 lesions in 101 patients who underwent TLR for SES restenosis were classified according to: (1) focal (lesion length < or = 10 mm) or non-focal restenosis (>10 mm); and (2) use of DES for TLR: (1) focal restenosis treated with DES (focal-DES, n=40); (2) focal restenosis treated by balloon angioplasty (focal-balloon, n=31); (3) non-focal restenosis with DES (non-focal-DES, n=17); and (4) non-focal restenosis by balloon angioplasty (non-focal-balloon, n=14). Re-restenosis and re-TLR were observed in 6 (19.4%) and 5 lesions (12.5%) of the focal-DES group, in 13 (65.0%) and 11 (35.5%) of the focal-balloon group, in 7 (50.0%) and 6 (35.3%) of the non-focal-DES group, and in 8 (61.5%) and 7 (50.0%) of the non-focal-balloon group, respectively (P<0.05 for restenosis and TLR between the focal-DES group and other groups). CONCLUSIONS: Re-DES implantation for focal DES restenosis results in lower re-restenosis and re-TLR rates compared to re-DES implantation for non-focal DES restenosis or conventional balloon angioplasty either for focal or non-focal DES restenosis.

BACKGROUND: Large-scale randomized trials demonstrate a high proportion of focal restenosis after drug-eluting stent (DES) implantation. On the other hand, recent reports have shown that in real-world practice a significant proportion of the restenosis is non-focal when DESs are used in unselected lesions. The present study evaluated angiographic patterns of restenosis after sirolimus-eluting stent (SES) implantation in Japan. METHODS AND RESULTS: Angiographic restenosis patterns of all consecutive restenotic lesions (n=124) after SES implantation were evaluated and classified according to the following scheme: focal (<or=10 mm in length), diffuse (restenosis >10 mm within the stent), proliferative (restenosis >10 mm in length extending outside the stent), and occlusive. There were 98 focal (79.0%), 15 diffuse (12.1%), and 5 proliferative restenoses (4.0%) and 6 total occlusions (4.8%). Focal intrastent restenosis was most dominant (42.7%). Proximal edge restenosis occurred in 22 lesions (17.7%). Multivariate analysis demonstrated diabetes mellitus (P<0.01) as an independent predictor of non-focal restenosis. CONCLUSIONS: Focal restenosis is predominant after SES implantation in real-world practice in Japan.

The polymer of paclitaxel-eluting stents (PES) plays an important role in controlling the release of paclitaxel. Damage to the polymer of a PES that is used in a patient has not been demonstrated, although in-vitro studies report disruption of it. The present case report describes damage to a PES as delivery through a calcified coronary artery was being attempted.

BACKGROUND: A lower maintenance dose of clopidogrel may be appropriate in Japanese patients because the maintenance dose of ticlopidine is lower in Japan than that used in the United States. METHODS AND RESULTS: A total of 126 patients with 153 lesions who consented to take 50-mg clopidogrel to prevent stent thrombosis were enrolled. There was 1 case of early stent thrombosis (0.65%). Side-effects of clopidogrel occurred in 5 patients (4.0%). CONCLUSION: This preliminary study shows that 50 mg clopidogrel may be acceptable in Japanese patients.

BACKGROUND: The loading dose of ticlopidine is 500 mg in both the US and Europe and 200 mg in Japan. A lower loading dose of clopidogrel might achieve adequate platelet inhibition in Japanese patients. METHODS AND RESULTS: Platelet aggregation was serially measured at baseline, and 2, 4, 6, and 8 h after 150-mg (n=20) and 300-mg (n=20) clopidogrel loading. Platelets were stimulated with 5 and 20 micromol/L adenosine diphosphate (ADP) and aggregation was assessed by optical aggregometry. Pretreatment ADP-induced platelet aggregation in the 150-mg clopidogrel group did not differ from that of the 300-mg group. The administration of 300-mg clopidogrel loading dose resulted in lower platelet aggregation 2 h after the administration (5 micromol/L ADP: 53+/-9% vs 61+/-12%, p<0.05 and 20 micromol/L ADP: 61+/-10% vs 68+/-9%, p<0.05). A lower platelet aggregation induced with 20 micromol/L ADP was still observed 4 h after the 300-mg clopidogrel loading (58+/-10% vs 65+/-9%, p<0.05). CONCLUSIONS: The 150-mg clopidogrel loading does not achieve rapid platelet inhibition. The 300-mg loading dose should be used to suppress platelet function rapidly even in Japanese patients undergoing coronary stent placement.

BACKGROUND: Damage to the polymer coating on sirolimus-eluting stents (SES) may occur when it is delivered through complex lesions such as calcified lesions. The present study evaluated damage to the polymer of SES that could not be delivered into lesions. METHODS: SES that could not be delivered into lesions were prospectively collected and examined using a scanning electron microscope. RESULTS: There were 5 undelivered SES. In all cases, moderate or severe calcification with and without vessel tortuosity were reasons for unsuccessful delivery. Scanning electron microscopy demonstrated damage to the polymer of 4 out of the 5 undelivered SES. CONCLUSION: Damage to the polymer coating of SES may occur when delivered through a calcified coronary artery.

BACKGROUND: Antiplatelet therapy in patients with sirolimus-eluting stents (SES) may be stopped because of bleeding or an invasive procedure. METHODS AND RESULTS: In 254 patients with SES, the incidence of discontinuation of antiplatelet therapy and subsequent adverse cardiac events was evaluated. Follow-up was complete for 97.2% of the population and mean follow-up was 15.6+/-8.9 months. Discontinuation of antiplatelet therapy occurred for 46 patients (18.1%): 1 case of late stent thrombosis (2.2%) occurred 10 days after cessation of therapy because of pulmonary hemorrhage 7 months after SES deployment. CONCLUSION: Discontinuation of antiplatelet therapy in patients with SES is not infrequent.

BACKGROUND: There is little information about the efficacy of ticlopidine plus aspirin after sirolimus-eluting stent (SES) implantation. METHODS AND RESULTS: The incidence of stent thrombosis was evaluated in 1,029 patients receiving ticlopidine and aspirin after SES deployment. Clinical follow-up was obtained in 98.9% (mean follow-up 17.0+/-7.9 months). Early stent thrombosis was observed in 5 patients (0.49%). There was 1 case each of late (0.1%) and very late stent thrombosis (0.1%). CONCLUSION: Late and very late stent thrombosis in Japanese patients receiving ticlopidine and aspirin after SES deployment occurs infrequently.