Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 67 , Issue 4
Showing 1-17 articles out of 17 articles from the selected issue
Review Article
  • Andreas Skyschally, Raimund Erbel, Gerd Heusch
    Type: None
    Subject area: None
    2003 Volume 67 Issue 4 Pages 279-286
    Published: 2003
    Released: March 25, 2003
    JOURNALS FREE ACCESS
    Atherosclerotic plaque rupture is a key event in the pathogenesis of acute coronary syndromes and during coronary interventions. However, it does not always result in complete thrombotic occlusion of the entire epicardial coronary artery with subsequent acute myocardial infarction; in milder forms the result can be embolization of atherosclerotic and thrombotic debris into the coronary microcirculation. This review summarizes the available morphological evidence for coronary microembolization in patients who died from coronary artery disease, most notably from sudden death, and then goes on to address the experimental pathophysiology of coronary microembolization in animal models of acute coronary syndromes and heart failure. Finally, the review presents the available clinical evidence for coronary microembolization in patients, highlights its key features (ie, arrhythmias, contractile dysfunction, infarctlets and reduced coronary reserve) and addresses its prevention by mechanical protection devices and glycoprotein IIb/IIIa antagonism. (Circ J 2003; 67: 279 - 286)
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Clinical Investigation
  • Implication of the J-LIT Study, a Large Scale Nationwide Cohort Study
    Yuji Matsuzawa, Toru Kita, Hiroshi Mabuchi, Masunori Matsuzaki, Noriak ...
    Type: None
    Subject area: None
    2003 Volume 67 Issue 4 Pages 287-294
    Published: 2003
    Released: March 25, 2003
    JOURNALS FREE ACCESS
    The Japan Lipid Intervention Trial (J-LIT) study, a nationwide cohort study utilizing the clinical practice of general physicians, was designed to clarify the relationship between the incidence of coronary heart disease and serum lipid concentrations during simvastatin therapy, as well as the safety of the therapy, in a large number of Japanese hypercholesterolemic patients. All the enrolled patients were treated with simvastatin. The current study analyzed the lipid lowering effect and safety of the low-dose simvastatin therapy used in the J-LIT study. Open-labeled simvastatin was given to 51,321 patients at an initial dose of mostly 5 mg/day. After 6 months of the treatment, the average serum total cholesterol (TC) and low density lipoprotein-cholesterol concentrations in all the patients followed up were reduced by 18.3% and 26.0%, respectively, and that of high density lipoprotein-cholesterol increased 2.3% on average. These concentrations were well maintained throughout the 6-year treatment period. A minority of patients (1.4%) unexpectedly had a remarkable reduction in TC concentration by more than 40%. Hyper-responders, even to low-dose statin, were found for the first time in this large-scale and long-term investigation. Overall adverse drug reactions occurred in 3.3% of subjects during the 6-year treatment, the major events being hepatic and musculoskeletal disorders, of which the incidence was less than 1%. Low-dose simvastatin therapy of 5 mg/day effectively controlled the serum TC concentration by reducing it by approximately 20% on average in hypercholesterolemic Japanese patients, a reduction that corresponds to the effect of simvastatin 20 mg/day in Western studies. In addition, the low incidence of drug-related adverse events in this study may be also related to the low dosage of simvastatin. (Circ J 2003; 67: 287 - 294)
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  • Ken Sugimoto, Hiroshi Ito, Katsuomi Iwakura, Masashi Ikushima, Akinobu ...
    Type: None
    Subject area: None
    2003 Volume 67 Issue 4 Pages 295-300
    Published: 2003
    Released: March 25, 2003
    JOURNALS FREE ACCESS
    The aim of this retrospective study was to assess whether intravenous nicorandil, a hybrid of NO and a KATP channel opener, in conjunction with percutaneous coronary intervention (PCI) improves the long-term prognosis in patients with acute myocardial infarction (AMI). Intravenous nicorandil has already been shown to improve the in-hospital prognosis of patients with anterior AMI. The study population consisted of 272 patients with a reperfused AMI who were admitted during a similar time interval, before (control; n=114) and after nicorandil treatment (n=158). In the nicorandil group, a 4 mg bolus injection was given, followed by 6 mg/h infusion for 24 h and then oral nicorandil at 15 mg/day for at least 1 month. In the patients with an anterior AMI, left ventricular (LV) function was better and the frequency of LV remodeling was lower after 3 months in the nicorandil group; however, in those with a non-anterior AMI, there were no differences in functional outcome and the frequency of LV remodeling between the 2 groups. The frequency of cardiac events was significantly lower in the nicorandil group, and the use of nicorandil was derived as a potential factor related to freedom from cardiac events (p<0.01, odds ratio = 0.27). Nicorandil treatment was associated with better myocardial perfusion and a better functional and clinical outcome than PCI alone, and this beneficial effect was maintained for a long time, particularly in patients with anterior AMI. (Circ J 2003; 67: 295 - 300)
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  • Hirofumi Soejima, Hisao Ogawa, Tomohiro Sakamoto, Shinzo Miyamoto, Ich ...
    Type: None
    Subject area: None
    2003 Volume 67 Issue 4 Pages 301-304
    Published: 2003
    Released: March 25, 2003
    JOURNALS FREE ACCESS
    The left ventricular ejection fraction (LVEF) is one of the major prognostic factors after acute myocardial infarction (AMI) and matrix metalloproteinase-1 (MMP-1) is an enzyme responsible for extracellular collagen degradation and remodeling. The present study investigated whether the concentration of serum MMP-1 was associated with the LVEF after AMI. Blood was sampled on admission, and at 24 h, 3 days, 7 days, 2 weeks and 4 weeks in 24 patients with their first AMI. Left ventriculography was performed 4 weeks after the onset of AMI and the LVEF was calculated by center line method. MMP-1 concentrations were higher at 7 days and at 2 weeks than on admission (p<0.001), and at 7 days (r=-0.655, p=0.0005) and at 2 weeks (r=-0.636, p=0.0008) were negatively correlated with the LVEF. The patients with AMI were divided into high and low LVEF groups according to the results of left ventriculography. Although there were no differences in the clinical characteristics between the 2 LVEF groups, the MMP-1 concentrations at 24 h (p<0.01), 7 days (p<0.01) and 2 weeks (p<0.05) were lower in the high LVEF group than in low LVEF group. A high concentration of MMP-1 at the subacute phase after AMI predicts advanced left ventricular remodeling. (Circ J 2003; 67: 301 - 304)
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  • Tomoyuki Hori, Taku Matsubara, Takaharu Ishibashi, Kazuyuki Ozaki, Kei ...
    Type: None
    Subject area: None
    2003 Volume 67 Issue 4 Pages 305-311
    Published: 2003
    Released: March 25, 2003
    JOURNALS FREE ACCESS
    The basal activity of nitric oxide (NO) is reduced in spastic arteries of patients with vasospastic angina (VSA). Elevated concentrations of ADMA are associated with reduced NO production and impaired endothelium-dependent vasodilatation. The aim of this study was to elucidate the role of ADMA and its relationship to NO end-products (NOx; nitrate + nitrite) during coronary circulation in patients with VSA. The plasma ADMA and NOx concentrations during coronary circulation were evaluated in 16 VSA and 16 control patients. Blood samples were obtained from the coronary sinus (V) and the ostium of the left coronary artery (A), and the (V-A) differences of ADMA and NOx were determined. The coronary sinus plasma ADMA concentration in patients with VSA was higher than that in the control. The coronary sinus - arterial (V-A) difference of NOx was negative in the VSA group and approximately zero in the control group (VSA group =-1.4 μmol/L, control group =-0.1 μmol/L, p=0.0005). Furthermore, in the VSA patients, there was a negative correlation between the (V-A) difference of NOx and the basal coronary artery tone at the site of spasm (r=-0.60, p=0.015). A significant negative correlation between the (V-A) differences of NOx and ADMA was observed in patients with VSA (r=-0.52, p<0.05), but not in those of the control. Higher ADMA concentrations might cause the reduced formation of NO that underlies the pathophysiology of coronary vasospasm. (Circ J 2003; 67: 305 - 311)
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  • Prediction of Induction of Ventricular Fibrillation by Noninvasive Methods
    Hiroshi Morita, Shiho Takenaka-Morita, Kengo Fukushima-Kusano, Makoto ...
    Type: None
    Subject area: None
    2003 Volume 67 Issue 4 Pages 312-316
    Published: 2003
    Released: March 25, 2003
    JOURNALS FREE ACCESS
    Ventricular fibrillation (VF) is induced in some asymptomatic patients with Brugada syndrome (BS), but the prognostic value of programmed electrical stimulation (PES) in such patients is controversial. The clinical characteristics of 41 asymptomatic BS patients, divided into 2 groups according to whether VF was induced by PES (inducible VF group: n=13, non-inducible VF group: n=28) were evaluated. ST levels in the right precordial leads were measured before and after administration of pilsicainide and the abnormal late potential (LP) was evaluated on the signal-averaged electrogram. The ST level at V2 at baseline in the inducible VF group was significantly higher than that in the non-inducible VF group (p<0.05). Pilsicainide induced significant ST segment elevation in both groups and the ST level after pilsicainide in the inducible VF group was higher than that in the non-inducible VF group (p<0.01). LP was more frequent in the inducible VF group than in the non-inducible VF group. The criterion of ST level >0.15 mV at baseline with pilsicainide-induced additional ST elevation >0.10 mV and positive LP showed high sensitivity (92%) and specificity (89%) for detection of PES-induced VF in asymptomatic BS patients. (Circ J 2003; 67: 312 - 316)
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  • Assessment of Asynchrony in Early- Systolic Wall Motion
    Satoshi Yamada, Taisei Mikami, Kaoru Komuro, Hisao Onozuka, Naotaka Sa ...
    Type: None
    Subject area: None
    2003 Volume 67 Issue 4 Pages 317-322
    Published: 2003
    Released: March 25, 2003
    JOURNALS FREE ACCESS
    To test the hypothesis that dobutamine-induced myocardial ischemia causes early-systolic asynchrony predominantly in the regional left ventricular wall, color kinesis (CK) images during dobutamine stress echocardiography (DSE) were recorded in 13 patients with coronary artery disease and in 10 patients without, all of whom showed normal wall motion at rest. Based on the visual interpretation of DSE and the angiographic findings, 21 segments in the short-axis images at the papillary muscle level were defined as ischemic, and 60 segments of the patients without coronary artery disease were defined as normal. The incremental fractional segmental area change (IFAC) was calculated at 33-ms intervals from the CK images. At the peak dose, IFACs during the first 33 and 33-67 ms were significantly lower in the ischemic segments than in the normal ones, and IFACs during 133-167, 200-233 and 233-267 ms were significantly higher in the ischemic segments. The ratio (peak/low dose) of the cumulative fractional area change at 100 ms gave the best sensitivity (= specificity) for differentiating the 2 groups (86%). Dobutamine-induced ischemia is characterized by an early-systolic asynchrony rather than a change in overall wall excursion and CK can provide an objective assessment of ischemia developing during DSE. (Circ J 2003; 67: 317 - 322)
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  • Isao Saito, Kunio Yonemasu, Fujiko Inami
    Type: None
    Subject area: None
    2003 Volume 67 Issue 4 Pages 323-329
    Published: 2003
    Released: March 25, 2003
    JOURNALS FREE ACCESS
    Because obesity is thought to play a key role in atherosclerosis through the low-grade chronic inflammation, the present study was designed to investigate associations of body mass index (BMI), body fat, and weight gain with optimized inflammation markers in 1,053 residents who were 40 years of age and older from a rural community (total population = 3,940 in 2000) in Japan. People reporting having a cold and those who did not undergo blood examinations were excluded. C-reactive protein (CRP), fibrinogen, serum albumin, and white blood cell (WBC) count were used as the markers for inflammation, body fat was calculated by a conventional method, and weight change since the age of 20 was assessed. The BMI and body fat significantly increased with CRP quartile, and its correlation coefficients to BMI or body fat were relatively high. Similar associations were found for fibrinogen, serum albumin and WBC. Multivariate-adjusted analysis found a high concentration of CRP was significantly associated with obesity, but attenuated the association in other markers. In an analysis restricted to people aged 40-69 years, body fat levels were more strongly associated with CRP and fibrinogen than with BMI only. Furthermore, only CRP concentrations were significantly elevated according to weight gain. Strong associations of CRP concentration with BMI, body fat, and weight gain were found among elderly Japanese, but not with fibrinogen, serum albumin or WBC. (Circ J 2003; 67: 323 - 329)
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  • Mizuhiro Arima, Tatsuji Kanoh, Atsutoshi Takagi, Kosei Tanimoto, Tetsu ...
    Type: None
    Subject area: None
    2003 Volume 67 Issue 4 Pages 330-333
    Published: 2003
    Released: March 25, 2003
    JOURNALS FREE ACCESS
    The incidence of acute pulmonary thromboembolism (APTE) in younger patients is extremely low compared with older patients, so the clinical features of these younger patients with APTE is unknown. In the present study, 8 patients with APTE who were less than 40 years old (YG) were compared with 40 patients who were more than 41 years of age (OG). All YG patients had coagulopathy compared with 3 patients in the OG (p<0.01). Deep venous thrombosis (DVT) occurred in all 8 patients in the YG compared with 19 patients in the OG (p<0.01). A higher incidence of patients whose symptoms occurred gradually was noted in the YG (p<0.05). There were no significant differences in clinical characteristics, initial symptoms, past history or other predisposing factors for venous thromboembolism between the 2 groups. Residual pulmonary hypertension was not noted in the YG. However, 1 patient in the YG had recurrent APTE, despite good warfarin control. This study demonstrated the frequency of gradual onset, coagulopathy and clinical signs of DVT in the YG and therefore more careful and long-term observation is necessary in such patients. (Circ J 2003; 67: 330 - 333)
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Experimental Investigation
  • Satoru Nishida, Hiroshi Nagamine, Yoko Tanaka, Go Watanabe
    Type: None
    Subject area: None
    2003 Volume 67 Issue 4 Pages 334-339
    Published: 2003
    Released: March 25, 2003
    JOURNALS FREE ACCESS
    The present study in rats investigated whether basic fibroblast growth factor (bFGF) plays an important role in cardioprotection against myocardial cell death and arrhythmias in acute myocardial infarction (AMI). After ligating the left coronary artery in 62 Wistar rats, 20 Ég of human recombinant bFGF was injected into the infarcted myocardium in 33 rats (group F), while saline was used for 29 control rats (group C). The development of ventricular tachyarrhythmias was assessed during the first 30 min of ischemia. After 24 h occlusion, the hearts of the surviving rats (group F: n=13, group C: n=10) were excised to assess minimum infarct wall thickness and infarct size, determine the number of TUNEL-positive cardiomyocytes and to analyze Bcl-2 and Bax expression by immunohistochemical staining and Western blotting. The incidence of ventricular tachycardia was higher in group C than in group F (p<0.05). The thinning ratio was higher in group F than in group C (p<0.05). There were fewer TUNEL-positive cardiomyocytes in the infarct border area in group F than in group C (p<.0001). Western blot analysis showed greater expression of Bcl-2 in group F than in group C (p<0.05), but similar expression of Bax in the 2 groups. In conclusion, intramyocardial administration of bFGF prevented ischemia-induced myocardial cell death and arrhythmias. (Circ J 2003; 67: 334 - 339)
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  • A Possible Suppressive Effect on Atrial Electrical Remodeling
    Jisho Kojima, Shinichi Niwano, Masahiko Moriguchi, Kazuko Ikeda, Kimia ...
    Type: None
    Subject area: None
    2003 Volume 67 Issue 4 Pages 340-346
    Published: 2003
    Released: March 25, 2003
    JOURNALS FREE ACCESS
    The heterogeneous process of atrial electrical remodeling (AER) in the canine rapid atrial stimulation model has been previously reported although it has been reported that a sodium channel blocker might suppress the shortening of the atrial effective refractory period (AERP), its effect on long-term electrical remodeling is unknown. In the present study, the effect of pilsicainide on AER was evaluated. The right atrial appendage (RAA) was paced at 400 beats/min for 2 weeks. In the RAA, Bachmann's bundle (BB), the right atrium near the inferior vena cava (IVC) and in the left atrium (LA), AERP, AERP dispersion (AERPd) and the inducibility of atrial fibrillation (AF) were evaluated at several time points of the pacing phase and the recovery phase (1 week). The same protocol was performed during the administration of pilsicainide (4.5 mg/kg per day) and the parameters were compared with the controls. In the control dogs, the AERP was significantly shortened by rapid pacing at all atrial sites studied and the AERP shortening (ΔAERP) was larger at the RAA and LA sites (p<0.03). However, pilsicainide decreased these ΔAERPs at all 4 atrial sites. AERPd was increased during the pacing phase whereas it was decreased during the recovery phase in the control dogs. In contrast, this pacing-induced AERPd was attenuated by the administration of pilsicainide. The AF inducibility was highest at the LA site in both groups, and the inducibility was lower in the pilsicainide group than the control group at all atrial sites. During the rapid pacing phase, the ventricular heart rate was significantly lower in the pilsicainide group than the control because of intra-atrial conduction block. In a canine rapid right atrial stimulation model, pilsicainide suppressed the shortening of the AERP at all atrial sites, possibly through the improvement of the hemodynamics as well as the action of the Na - Ca exchanger. (Circ J 2003; 67: 340 - 346)
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  • Kenji Iino, Hiroyuki Watanabe, Takashi Saito, Satoshi Kibira, Toshihik ...
    Type: None
    Subject area: None
    2003 Volume 67 Issue 4 Pages 347-353
    Published: 2003
    Released: March 25, 2003
    JOURNALS FREE ACCESS
    The purpose of this study was to test the hypothesis that tumor necrosis factor-α (TNF-α) rapidly antagonizes the β-adrenergic responses of the chloride current and to clarify the intracellular mechanisms responsible for the anti-adrenergic action. The whole-cell patch-clamp technique was used to monitor the anti-adrenergic effects of TNF-α on the cAMP-dependent chloride current (ICl) recorded from isolated guinea-pig ventricular myocytes. Ramp pulses (±120 mV; dv/dt = ±0.4 V/s) were applied from the holding potential of -40 mV. TNF-α rapidly (<15 min) inhibited the isoproterenol (Iso, 0.1 μmol/L)-induced ICl in a concentration-dependent manner (30-1,000 U/ml, IC 50 = 144 U/ml, n=30). The inhibitory action of TNF-α was also observed when ICl had been previously stimulated by 1 μmol/L forskolin (n=5). Prior exposure of myocytes to 5 μg/ml pertussis toxin (PTX) hardly affected the anti-adrenergic action of TNF-α (n=4). However, when ICl was induced by both 8-bromo-cAMP (100 μmol/L) and isobutylmethylxanthine (0.1 mmol/L), TNF-α (1,000 U/ml) failed to decrease ICl amplitude (n=5). Prior exposure of myocytes to 5 mg/ml pertussis toxin (PTX) hardly affected the anti-adrenergic action of TNF-α (n=4). Furthermore, despite of the presence of nitro-L-arginine methyl ester (0.1 mmol/L), a nitric oxide synthase (NOS) inhibitor, TNF-α reversed the Iso-induced increase in ICl (n=5). These results suggest that TNF-α rapidly antagonizes the β-adrenergic responses of ICl by reducing cAMP concentration. This anti-adrenergic action is mediated by neither the PTX-sensitive G proteins regulatory pathway nor constitutive NOS activation. (Circ J 2003; 67: 347 - 353)
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Case Report
  • Ayaka Kobashi, Michihiro Suwa, Tomomi Nakamura, Takahide Ito, Taiko Ho ...
    Type: None
    Subject area: None
    2003 Volume 67 Issue 4 Pages 354-356
    Published: 2003
    Released: March 25, 2003
    JOURNALS FREE ACCESS
    Congenitally corrected transposition of the great arteries (CCTGA) is a rare congenital heart disease characterized by atrioventricular (AV) and ventriculo-arterial discordance;1 that is, the left ventricle supports the pulmonary circulation and the right ventricle supports the systemic circulation. The most common cardiac anomalies in CCTGA include ventricular septal defect, pulmonary outflow tract obstruction and abnormalities of the systemic AV valve. 1 The dysfunction of the systemic ventricle occurs with increasing frequency in older patients with CCTGA, independent of their commonly associated structural defects.2-4 We report a patient with CCTGA undergone the partial ventriculectomy for his systemic ventricular dysfunction. (Circ J 2003; 67: 354 - 356)
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  • Hiromichi Fujii, Shigefumi Suehiro, Toshihiko Shibata, Takanobu Aoyama ...
    Type: None
    Subject area: None
    2003 Volume 67 Issue 4 Pages 357-358
    Published: 2003
    Released: March 25, 2003
    JOURNALS FREE ACCESS
    A Mallory - Weiss tear occurred as a complication of intraoperative transesophageal echocardiography carried out in a 62-year-old man who underwent coronary artery bypass grafting. Left ventricular function was monitored in the transgastric short-axis view. Postoperative esophagogastroscopy revealed a Mallory - Weiss tear at the gastroesophageal junction and erosions in the cardia, presumably secondary to contact pressure by the echoprobe and ultrasonic thermal injury. When not actively imaging, the echoprobe should be left free in the esophagus with the acoustic power off. (Circ J 2003; 67: 357 - 358)
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  • You-Bin Deng, Chun-Lei Li, Qing Chang
    Type: None
    Subject area: None
    2003 Volume 67 Issue 4 Pages 359-361
    Published: 2003
    Released: March 25, 2003
    JOURNALS FREE ACCESS
    A 28-year-old man developed exertional dyspnea and peripheral edema 1 year after the initial blunt trauma to the chest. The diagnosis of pseudoaneurysm (PSA) of the ascending aorta was made based on the echocardiographic finding of a large echo-free space that communicated with the ascending aorta through the defect in the ascending aortic wall. The PSA caused a right ventricular inflow obstruction with increased diastolic transtricuspid blood flow velocity up to 2.7 m/s. Following the excision of the PSA and repair of the communication between it and the ascending aorta, the sizes of the right atrium and right ventricle, and the diastolic transtricuspid blood flow velocity, normalized. (Circ J 2003; 67: 359 - 361)
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  • Nobuyuki Negoro, Jin Nariyama, Atsushi Nakagawa, Hiroshi Katayama, Tai ...
    Type: None
    Subject area: None
    2003 Volume 67 Issue 4 Pages 362-365
    Published: 2003
    Released: March 25, 2003
    JOURNALS FREE ACCESS
    Acute coronary syndrome occurred in 2 young adults who had a history of Kawasaki disease (KD), but few other coronary risk factors. The first patient was a 27-year-old male with acute myocardial infarction without stenosis detected by coronary arteriography 4 years earlier. Emergency coronary arteriography showed occlusion of the right coronary artery. Aspiration-thrombectomy and rescue balloon angioplasty were successfully performed. The second patient was a 32-year-old male with unstable angina. Right coronary arteriography showed total occlusion with severe calcification. Left coronary arteriography showed 99% stenosis at the proximal site of the circumflex artery, and a directional coronary atherectomy was performed. Histological examination of a specimen from this site revealed a lipid core, macrophages, and smooth muscle cells. Restenosis was not observed on follow-up coronary arteriography after 5-6 months in either case. The coronary stenosis in each case was probably caused by accelerated atherosclerosis at the site without aneurysm as it seemed to be `normal' on arteriography. Conventional catheter intervention was effective treatment. The sequelae of KD should be recognized as independent coronary risk factors. (Circ J 2003; 67: 362 - 365)
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Rapid Communication
  • Angioscopic Findings in Human Coronary Arteries
    Shinsuke Nanto, Masaaki Uematsu, Tomoki Ohara, Takakazu Morozumi, Juni ...
    Type: None
    Subject area: None
    2003 Volume 67 Issue 4 Pages 366-368
    Published: 2003
    Released: March 25, 2003
    JOURNALS FREE ACCESS
    Little is known about the alterations of the vascular surface after radiation therapy for in-stent restenosis in humans, even though animal experiments suggest that delayed healing of the neointima is a cause of late thrombosis. Coronary angioscopy, together with coronary angiography, was performed at 3 months follow-up of 7 patients with in-stent restenosis who underwent β-radiation therapy. Minimal lesion diameter (MLD) of the lesion increased from 1.00±0.30 mm (immediately before) to 2.44±0.39 mm (immediately after) and the MLD was well maintained 3 months later (2.34±0.62 mm) without any cases of restenosis. In 5 patients, the intima was so thin that some stent struts could be seen through it on angioscopy and in 2 of those, the intima over the stent had disappeared and 1 patient showed ulceration of the vascular wall beneath the stent. After intracoronary radiation therapy, the intima can become so thin that some stent struts are exposed to the lumen, which may be related to the occurrence of late thrombosis. Accordingly, patients who are treated with intracoronary radiation therapy may need long-term antiplatelet therapy. (Circ J 2003; 67: 366 - 368)
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