Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Volume 70 , Issue 11
Showing 1-28 articles out of 28 articles from the selected issue
Clinical Investigation
  • Gaku Nakazawa, Kengo Tanabe, Jiro Aoki, Yoshinobu Onuma, Hirosada Yama ...
    2006 Volume 70 Issue 11 Pages 1367-1371
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background Studies in Western countries have shown that sirolimus-eluting stents (SES) are clinically effective in the real world, but the detailed serial angiographic analyses are limited to some complex lesions. In addition, the efficacy of SES has not been fully investigated in a Japanese population. Methods and Results The study population consisted of 249 consecutive unselected patients who underwent percutaneous coronary intervention (PCI) with SES. Clinical and angiographic follow-up were evaluated at 8 months. Clinical follow-up was obtained in all patients and angiographic follow-up was obtained in 228 patients (91.6%) with 272 lesions (91.0%). Major adverse cardiac events were documented in 44 patients (17.7%). There were 2 stent thromboses within 24 h and 11 days after PCI (0.8%). Late lumen loss in the proximal edge, in-stent, and distal edge was 0.06±0.44 mm, 0.26±0.60 mm, and -0.05±0.30 mm, respectively. The rate of angiographic in-segment binary restenosis was 14.0% (proximal edge: 3.3%, in-stent: 10.7%, distal edge: 0.7%). By multivariate analysis, an increased risk of restenosis was significantly associated with hemodialysis, diabetes, lesion length, and impaired left ventricular ejection fraction. Conclusion In accordance with previous reports, SES is considered to be feasible, safe and effective based on the results in an unselected Japanese population. (Circ J 2006; 70: 1367 - 1371)
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  • Akio Ogawa, Yoshihiko Seino, Teruyo Yamashita, Ken-ichi Ogata, Teruo T ...
    2006 Volume 70 Issue 11 Pages 1372-1378
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background N-terminal pro-B-type natriuretic peptide (NT-proBNP) is elevated in patients with acute coronary syndrome (ACS), and is a powerful predictor of long-term mortality. Differences in the clinical utility and pathophysiological implication of NT-proBNP and conventional cardiac markers in patients with ST elevation (STE) vs non-STE (NSTE) ACS were investigated in the present study. Methods and Results Ninety consecutive patients admitted with acute chest pain and a diagnosis of unstable angina or acute myocardial infarction were analyzed. Patients with ≥Killip class II were excluded to focus on the effect of myocardial ischemia on the release of cardiac markers. The markers were measured on admission and analyzed according to the time from onset. Conventional cytosolic marker (creatine kinase-MB) and myofibril marker (troponin T: TnT) were both significantly higher in STE-ACS patients compared with NSTE-ACS patients. Conversely, NT-proBNP was significantly higher in NSTE-ACS patients than STE-ACS especially within 3 h of onset, suggesting a larger ischemic insult despite the smaller extent of myocardial necrosis compared with STE-ACS patients. There was no significant correlation between NT-proBNP level and left ventricular ejection fraction (LVEF) obtained at acute-phase echocardiography in either NSTE-ACS patients (LVEF 57.7±11.2%) or STE-ACS patients (LVEF 55.1±12.7%). Comparison between NT-proBNP and TnT levels revealed a marked difference of elevations, with significantly augmented elevation of NT-proBNP (p<0.001) in NSTE-ACS patients as compared with prominent elevation of TnT in STE-ACS patients. Conclusions NT-proBNP is an early sensitive marker of myocardial ischemia that rises much higher in the earlier phase as compared with conventional markers of myocardial damage, especially in NSTE-ACS patients. (Circ J 2006; 70: 1372 - 1378)
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  • Hyungseop Kim, Dong Heon Yang, Yongwhi Park, Juyup Han, Hyunsang Lee, ...
    2006 Volume 70 Issue 11 Pages 1379-1384
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background Cardiac biomarkers, including high-sensitivity C-reactive protein (hs-CRP), N-terminal proB-type natriuretic peptide (NT-proBNP) and cardiac troponin-I (Tn-I), have been associated with an adverse outcome in patients with acute coronary syndrome (ACS). Thus, in the present study the incremental prognostic value of these cardiac biomarkers was evaluated for risk stratification of ACS. Methods and Results The baseline levels of hs-CRP, NT-proBNP and Tn-I were measured in 215 patients (140 males; 65±46 years) with ACS: ST-elevation myocardial infarction (STEMI): 56; non-ST-elevation myocardial infarction (NSTEMI): 98; unstable angina (UA): 61. The patients were retrospectively followed up for a mean of 246 days. There were 24 cardiac events: STEMI: 1, NSTEMI: 6, UA: 6, chronic heart failure: 1, death: 10. The baseline levels of hs-CRP and NT-proBNP were significantly higher in the patients with cardiac events than in those without events. After adjustment for major clinical prognostic factors, hs-CRP and NT-proBNP remained significantly independent predictors for cardiac events. Patients with hs-CRP level >3.5 mg/L and NT-proBNP level >500 pg/ml had an 11-fold higher risk for cardiac events than those with hs-CRP level ≤3.5 mg/L and NT-proBNP level ≤500 pg/ml. Conclusion The combination of both cardiac markers has an incremental value in the risk stratification of patients with ACS. (Circ J 2006; 70: 1379 - 1384)
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  • Satoshi Isobe, Yasuo Takada, Akitada Ando, Satoru Ohshima, Kiyoyasu Ya ...
    2006 Volume 70 Issue 11 Pages 1385-1391
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background The physiological mechanism of the increase in the electrocardiographic (ECG) R-wave voltage after revascularization in patients with acute myocardial infarction (MI) needs to be elucidated. Methods and Results One hundred and thirty-eight MI patients (83: anterior MI, 45: inferior MI, 10: lateral MI) underwent ECG and echocardiography in both the acute and subacute phases after emergency revascularization, as well as a resting thallium-201/iodine-123 15-p-iodophenyl-3-(R,S)-methyl pentadecanoic acid myocardial scintigraphy in the acute phase. The total sum of the R-wave voltage (ΣR) was calculated over multiple leads on ECG for each infarcted lesion. Scintigraphic defect on each tracer was expressed as the percentage (%) defect of the total left ventricular (LV) myocardium. The % defect-discordance on both images in the acute phase and the % increase in ΣR and the absolute increase in LV ejection fraction from the acute to the subacute phase (ΔEF) were also calculated. The ΣR in the subacute phase was significantly greater than that in the acute phase (p<0.0001). The % increase in ΣR significantly correlated with the ΔEF (r=0.57, p<0.0001). The % increase in ΣR also correlated with the % defect-discordance (r=0.68, p<0.0001). Conclusions The increase in the ECG R-wave voltage reflects not only the improvement in myocardial perfusion but also the presence of salvaged myocardium after revascularization in acute MI patients. (Circ J 2006; 70: 1385 - 1391)
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  • Xingpeng Liu, Deyong Long, Jianzeng Dong, Fuli Hu, Ronghui Yu, Ribo Ta ...
    2006 Volume 70 Issue 11 Pages 1392-1397
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background Stepwise segmental pulmonary vein isolation (SPVI) and circumferential pulmonary vein isolation (CPVI) have been developed to treat patients with atrial fibrillation (AF), but the preferable approach for paroxysmal AF (PAF) has not been established. Methods and Results One hundred and ten patients with symptomatic PAF were randomized into a stepwise SPVI group (n=55) or CPVI group (n=55). Systemic SPVI combined with left atrial linear ablation tailored by inducibility of AF was performed in the stepwise SPVI group. Circumferential linear ablation around the left and right-sided pulmonary veins (PVs) guided by 3-dimensional electroanatomic mapping was performed in the CPVI group. The endpoints of ablation are non-induciblity of AF in the stepwise SPVI group and continuity of circular lesions combined with PV isolation in the CPVI group. After the initial procedures, atrial tachyarrhythmis (ATa) recurred within the first 3 months in 23 of the 55 patients (41.8%) who underwent stepwise SPVI and in 20 of the 55 patients (36.4%) who had CPVI (p=0.69). Repeat procedures were performed in 7 patients from the stepwise SPVI group and 5 from the CPVI group (p=0.76). During the 3-9 months after the last procedure, 46 patients (83.6%) from the CPVI group and 43 (78.2%) from the stepwise SPVI group did not have symptomatic ATa while not taking anti-arrhythmic drugs (p=0.63). Severe subcutaneous hematoma or PV stenosis occurred in 3 patients. Conclusions The efficacy of stepwise SPVI is comparable to that of CPVI for patients with PAF. (Circ J 2006; 70: 1392 - 1397)
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  • Noriko Inoue, Toshiyuki Ishikawa, Shinichi Sumita, Tsukasa Kobayashi, ...
    2006 Volume 70 Issue 11 Pages 1398-1401
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background Atrial fibrillation (AF) is a common arrhythmia in patients with an implanted pacemaker, but the role of atrial pacing in preventing AF is still unclear. Methods and Results Sixty-six patients (67.8±12.1 years) were enrolled: 54 with sick sinus syndrome (SSS), 11 with atrioventricular blocks (AVB), and 1 with SSS and AVB. The prevalence of AF was investigated. In 22 patients with AF, the AF burden was estimated under "back-up pacing" (40-50 beats/min), then under "atrial pacing" (60-85 beats/min). The prevalence of AF in the SSS group tended to be higher than that in the AVB group (48.1% vs 18.2%, p=0.06). The AF burden in patients with a percentage of atrial pacing (% atrial pacing) <50% was significantly greater than that in patients with % atrial pacing ≥50% (12.5±21.1% vs 4.2±10.3%, p<0.05). AF disappeared immediately after "atrial pacing" in 4 patients (18.2%). In 9 patients (40.9%), the AF burden decreased gradually, and AF disappeared in 6 patients (27.3%) after 207.9±130.2 days. Conclusion The prevalence of AF may be higher in patients with SSS than in those with AVB. Atrial pacing has a preventive effect on AF, and the effect of atrial pacing is not always immediate but is progressive in some patients. (Circ J 2006; 70: 1398 - 1401)
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  • Hajime Nishio, Misa Iwata, Koichi Suzuki
    2006 Volume 70 Issue 11 Pages 1402-1406
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background Mutations of the cardiac ryanodine receptor type 2 (RyR2) gene are known to cause effort-induced polymorphic ventricular arrhythmia, syncope and sudden death. Methods and Results The possible mutations in the RyR2 gene were examined in 18 autopsy cases of sudden unexplained death (SUD). Two cases were found to have the heterozygous missense mutation in exon 14 (nucleotide change C1258T, coding effect R420W). Both cases showed mild fatty infiltration of the right ventricular apex. Interestingly, 1 case showed an enlarged thymus with accompanying hypertrophy of the tonsils and mesenteric lymph nodes. In addition, a narrowing of the aorta was observed in this case. These phenotypic characteristics are consistent with status thymico-lymphaticus, which combines sudden death with an enlargement of lymphoid organs and hypoplasia of the cardiovascular system. The second case also displayed some characteristics of status thymico-lymphaticus. Conclusion The R420W mutation has already been reported in families with juvenile sudden death and may be causative of sudden death in our cases. Postmortem molecular screening of the RyR2 gene could be useful for investigation for cause of death in SUD. The possible association of the RyR2 mutation with status thymico-lymphaticus is discussed. (Circ J 2006; 70: 1402 - 1406)
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  • Keisuke Yamazaki, Hajime Terada, Hiroshi Satoh, Kensuke Naito, Akihiro ...
    2006 Volume 70 Issue 11 Pages 1407-1414
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background Arsenic trioxide (As2O 3) is a new promising regimen for patients with a relapse of acute promyelocytic leukemia (APL), but causes life-threatening arrhythmias. This study aimed to investigate the incidence and mechanism of arrythmogenesis caused by As2O3. Methods and Results Standard 12-lead ECGs were monitored throughout As2O3 therapy in 20 APL patients. As2O 3 (0.15 mg/kg) significantly prolonged the corrected QT interval (QTc: 445±7 to 517±17 ms, means±SE, p<0.01), and also increased the QTc dispersion and transmural dispersion of repolarization. Non-sustained ventricular tachycardias and torsades de pointes occurred in 4 and 1 patients, respectively. The action potentials and isometric contraction were measured in guinea pig papillary muscles during As2O 3 perfusion (350 μmol/L). The action potential duration was prolonged (APD90: 150±11 to 195±12 ms at 60 min, p<0.01, n=5) and perfusion of As2O3 in a low K+ solution with a low stimulation rate augmented the prolongation of APD, and provoked early after-depolarizations and triggered activities. The prolonged exposure to As2O3 induced muscle contracture, aftercontractions, triggered activities and electromechanical alternans. Tetrodotoxin or butylated hydroxytoluene partially prevented the As2O3-induced prolongation of APD. Conclusions The prolonged QTc and spatial heterogeneity are responsible for the As2O3-induced ventricular tachyarrhythmias. In addition to prolongation of the APD, cellular Ca2+ overload and lipid peroxidation might contribute to the electrophysiological abnormalities caused by As2O3. (Circ J 2006; 70: 1407 - 1414)
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  • Masami Nishino, Shiro Hoshida, Yasuyuki Egami, Isao Kondo, Ryu Shutta, ...
    2006 Volume 70 Issue 11 Pages 1415-1420
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background This study was undertaken to investigate whether coronary flow reserve (CFR) using coronary sinus flow (CSF), which can be measured by transesophageal Doppler echocardiography (TEDE), especially when contrast enhanced, is useful in evaluating microvascular dysfunction in patients with diabetes mellitus (DM). Methods and Results CSF recordings using contrast enhanced TEDE were performed before and after adenosine triphosphate infusion (0.15 mg · kg-1 · min-1) in 16 patients with type 2 DM and diabetic retinopathy and in 13 non-DM patients (control). Coronary angiography revealed normal epicardial coronary arteries. CFR was defined as the ratio of the antegrade flow velocity time integral in hyperemic conditions and basal levels. Clear envelopes of CSF were obtained in all DM patients using contrast-enhanced TEDE. CFR using CSF in the DM group was significantly decreased compared with the control group (1.4±0.4 vs 2.1±0.5, p<0.01), but there were no significant differences of age, ejection fraction, rate of hypertension and hypercholesterolemia between the 2 groups. Using 1.7 of CFR as the cut-off value, diabetic microvascular dysfunction could be detected with 82% sensitivity and 83% specificity. Conclusions CFR calculated by CSF using contrast-enhanced TEDE may be useful for evaluating diabetic microvascular dysfunction. (Circ J 2006; 70: 1415 - 1420)
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  • Tomohiro Nishinaka, Heinrich Schima, Wilfried Roethy, Angela Rajek, Ch ...
    2006 Volume 70 Issue 11 Pages 1421-1425
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background The clinical application of the DuraHeart (Terumo Heart Inc, USA) has begun in Europe as a clinical trial of a third-generation implantable centrifugal blood pump. Four successful clinical implants are presented. Methods and Results Four male patients had end-stage left heart failure and received a DuraHeart VAD as a left ventricular assist device for bridge-to-transplantation. The pump showed good performance with flow rates of 4.9±0.5 L/min after gradual weaning of extracorporeal circulation. The pump flow was then maintained at 6.1±0.5, 5.5±0.3, 5.5±0.1, 5.7±0.1, 5.5, 6.4 and 6.5 L/min at the 1st, 4th, 8th, 12th, 16th, 20th and 24th postoperative week, respectively. No significant elevation of mean plasma-free hemoglobin was detected. The patients were discharged on the 18th, 42nd, 41st and 31st postoperative day, respectively, and all were successfully transplanted on the 202nd, 84th, 128th and 96th postoperative day, respectively. At the time of transplant surfaces of the removed pumps were free from thrombus formation, although intraventricular pannus growth was observed around the inflow cannulae in all patients. Conclusion The DuraHeart VAD showed stable and sufficient circulatory support for the bridge-to-transplant procedure in this cohort of 4 patients. (Circ J 2006; 70: 1421 - 1425)
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  • Akira Sezai, Mitsumasa Hata, Shinji Wakui, Motomi Shiono, Nanao Negish ...
    2006 Volume 70 Issue 11 Pages 1426-1431
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background The aim of the present study was to evaluate the efficacy of α-human atrial natriuretic peptide (hANP) in cardiac surgery under cardiopulmonary bypass (CPB). Methods and Results A prospective randomized study was conducted with 150 patients who underwent scheduled coronary artery bypass grafting to compare a group of patients receiving 0.02 μg · kg-1 · min-1 of hANP from the initiation of CPB with a group not receiving hANP. Hemodynamics, levels of atrial and brain natriuretic peptides (BNP), angiotensin-II and aldosterone, renin activity, and left ventricular (LV) function were examined. The hANP group showed significantly lower renin activity and lower levels of angiotensin-II and aldosterone during the early postoperative period, compared with the non-hANP group. The incidence of postoperative ventricular arrhythmia and the postoperative peak level of creatine kinase-MB were significantly lower in the hANP group. BNP at 1 month after surgery and measures of LV function were also significantly lower in the hANP group. Conclusions Low-dose continuous infusion of hANP during cardiac surgery not only had a compensatory effect for the imperfections of CPB during the early postoperative period but also an inhibitory effect on postoperative LV remodeling and a reduction in ischemia/reperfusion injury. hANP should be part of the postoperative care for cardiac surgery. (Circ J 2006; 70: 1426 - 1431)
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  • Pelin Karaca, Cüneyt Konuralp, Yavuz Enc, Asuman Süzer, Onur ...
    2006 Volume 70 Issue 11 Pages 1432-1436
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background Aprotinin is a serine protease inhibitor used extensively in cardiac operations to reduce postoperative bleeding. It also has cardioprotective effects in ischemia/reperfusion injury. In this study, the effects of aprotinin on the release of cardiac markers were evaluated in patients who had good ventricular function and were undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB). Methods and Results Eighty male patients with an ejection fraction ≥40%, were randomized into either an aprotinin (Group-I; n=40) or control (Group-II; n=40) group. Patients in the aprotinin group received the full Hammersmith doses of aprotinin (2×106 KIU pre-CPB, 2×106 KIU at pump prime, 500,000 KIU/h during CPB), whereas the patients in the control group received only saline solutions. Cardiac troponin-I (cTnI) levels were measured before surgery, immediately after surgery, and at postoperative 6th, 12th, 24th h and 5th day. Creatine kinase (CK)-MB measurements were performed at the same time except for the postoperative 5th day. Cardiac index (CI), mixed venous oxygen saturation and lactate dehydrogenase (LDH) measurements were also performed. Conclusion Although all patients were in reasonable condition, less myocardial enzyme leakage occurred on the aprotinin group, suggesting that aprotinin has a protective effect on the myocardium beyond that achieved with blood cardioplegia and systemic hypothermia. Because of aprotinin's effects on multiple targets of metabolism, its protective value might increase in more complicated cases. (Circ J 2006; 70: 1432 - 1436)
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  • Koichi Fujita, Hitoshi Nishizawa, Tohru Funahashi, Iichiro Shimomura, ...
    2006 Volume 70 Issue 11 Pages 1437-1442
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background The metabolic syndrome (MetS) is a major target for prevention of atherosclerotic cardiovascular diseases and visceral fat accumulation is an underlying component of MetS. The aim of this study was to investigate the association of systemic oxidative stress with visceral fat accumulation and MetS. Methods and Results The study group consisted of Japanese men (n=44; 51.2±11.4 years) and women (n=61; 55.4 ±13.4 years). Urinary 8-epi-prostaglandin F2α (8-epi-PGF2 α) concentration, a biomarker of systemic oxidative stress, was significantly high in the subjects with MetS. As the urinary concentration of 8-epi-PGF2α increased, the number of criteria for MetS were significantly met (abdominal obesity, hypertriglyceridemia, low high-density lipoprotein-cholesterol, hypertension, and high fasting glucose). Among parameters associated with MetS, the correlation coefficient of visceral fat area (VFA) with urinary 8-epi-PGF2α concentration was the highest (r=0.636, p<0.0001). In non-obese subjects, the correlation coefficient of VFA with urinary 8-epi-PGF2α concentration was higher (r=0.728, p<0.0001), although there was no significant correlation between subcutaneous fat area and urinary 8-epi-PGF2 α. Stepwise multiple regression analysis identified VFA as the strongest and independent determinant of urinary 8-epi-PGF2 α (p<0.0001) followed by adiponectin (p=0.0212) and, high sensitive C-reactive protein (p=0.0365). Conclusions Systemic oxidative stress, as measured by urinary 8-epi-PGF2α , is strongly associated with visceral fat accumulation and MetS. (Circ J 2006; 70: 1437 - 1442)
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  • Makoto Takeuchi, Tohru Matsushita, Shunji Kurotobi, Tetsuya Sano, Shig ...
    2006 Volume 70 Issue 11 Pages 1443-1445
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background Myocardial damage occurs in the late stage of Kawasaki disease (KD) regardless of whether coronary artery lesions (CALs) are present. Methods and Results A signal-averaged electrocardiogram (ECG) was performed in 23 patients who were in the late stage of KD (CAL was found in 12 and no CAL (non-CAL) was found in 11) and 10 healthy controls. Filtered QRS duration and the root-mean-square voltage in the last 40 ms of the QRS complex were measured using time-domain analysis. Additionally, the area ratio (AR), (area of 20-50 Hz)/(area of 0-20 Hz) ×100, was calculated by frequency domain analysis. These findings were compared with the clinical data and histopathological findings. In time-domain analysis, there were no significant differences among the 3 groups. In frequency domain analysis, the AR in CAL was significantly higher than that in the other 2 groups. Furthermore, all 4 patients who underwent an endomyocardial biopsy showed a high AR and abnormal histopathological features. Conclusions The findings of the present study suggest that patients in the late stage of KD have abnormal findings on signal-averaged ECG even without stenotic lesions, arrhythmia or ischemia, a condition that might reflect histopathological changes in the myocardium in the late stage of KD. (Circ J 2006; 70: 1443 - 1445)
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  • Naoki Ohashi, Masaki Matsushima, Masanobu Maeda, Shigeo Yamaki
    2006 Volume 70 Issue 11 Pages 1446-1450
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background Down syndrome patients are characterized by early progression of pulmonary vascular obstructive disease because of insufficient thickness of the pulmonary arterial media. For those with congenital heart disease (CHD) associated with pulmonary hypertension (PH), a 2-stage procedure of pulmonary artery banding (PAB) and then intracardiac repair (ICR) in early infancy is performed to prevent such pulmonary vascular diseases in early infancy. Methods and Results The subjects were 16 patients with Down syndrome who underwent lung biopsy during PAB and ICR. PAB was planned to be performed in early infancy and ICR approximately 1 year later. Efficacy of the 2-stage procedure was retrospectively examined with reference to pulmonary vascular disease and pulmonary diseases. The index of pulmonary vascular disease at PAB fulfilled the indication for ICR, and it was significantly lower at ICR than at PAB (p=0.0469); furthermore, PAB prevented progression of pulmonary diseases. Conclusions The results of the lung biopsies support the safety of the 2-stage procedure and show that it is effective for Down syndrome patients with CHD and PH. (Circ J 2006; 70: 1446 - 1450)
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  • Nobuaki Kokubu, Kazufumi Tsuchihashi, Satoshi Yuda, Mamoru Hase, Marik ...
    2006 Volume 70 Issue 11 Pages 1451-1456
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background There is considerable interest in the pleiotropic pharmacological action of sarpogrelate hydrochloride, a novel selective serotonin 2A receptor antagonist. In the present study the persistent insulin-sensitizing effects of sarpogrelate were investigated in non-diabetic and non-medicated diabetic patients with peripheral artery disease (PAD). Methods and Results Indices of insulin resistance (IR) (fasting immunoreactive insulin (IRI) and calculated homeostasis model assessment (HOMA-R)) and adiponectin were measured before and after 2 weeks of sarpogrelate administration (300 mg/day) in 24 patients (19 men, 76±9 years) with PAD. Sixteen of the 24 patients were examined after 3 months of treatment for assessment of the chronic effect of sarpogrelate on IR. After 2 weeks of treatment, significant decreases in fasting IRI (p=0.03) and HOMA-R (p=0.024), but not in adiponectin, were observed. After 3 months of treatment, significant decreases in fasting IRI (16.0±10.3 vs 9.2±2.0 μU/ml, p=0.03) and HOMA-R (4.30±2.83 vs 2.40±0.74, p=0.025) were maintained. Furthermore, adiponectin was significantly increased (8.11±4.13 vs 9.64±4.37 μg/ml, p=0.027). All of the examined HOMA-R had a significant correlation with all of the examined adiponectin (p<0.001, r=-0.441). Conclusions Sarpogrelate has a persistent insulin-sensitizing effect through adiponectin modification and might be beneficial for anti-atherosclerotic therapy, at least, in non-diabetic and non-medicated diabetic patients with PAD. (Circ J 2006; 70: 1451 - 1456)
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  • Akira Koike, Masayo Hoshimoto, Akihiko Tajima, Osamu Nagayama, Kaori Y ...
    2006 Volume 70 Issue 11 Pages 1457-1461
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background In a recent study the indexes of cerebral oxygenation decreased during maximal exercise in nearly half of all patients with left ventricular dysfunction. Whether these levels decrease severely enough to influence mental status or level of consciousness was evaluated in the present study. Methods and Results Forty-two patients with idiopathic dilated cardiomyopathy (IDC) and 29 healthy subjects underwent a symptom-limited maximal exercise test. The cerebral oxyhemoglobin (O2Hb) and tissue oxygenation index (TOI) were continuously monitored using near-infrared spectroscopy. The changes in O2Hb and TOI were also measured in 7 subjects: 2 who experienced episodes of reduced consciousness caused by sudden decreases in blood pressure during exercise recovery and 5 who exhibited sustained ventricular tachycardia during an electrophysiological study. The change in cerebral O2Hb during exercise in patients with IDC averaged 0.38±3.39 μmol/L, significantly lower than in the normal subjects (4.30±4.47 μmol/L, p<0.0001). The cerebral O2Hb decreased during exercise in 18 of 42 patients with IDC. The change in cerebral TOI in the IDC patients during exercise was significantly less than that in the normal subjects (-2.0±4.7 vs 2.1±5.8%, p=0.002). The mean decreases in cerebral O2Hb and TOI were -5.34 μmol/L and -9.7%, respectively, in the patients with reduced consciousness during exercise recovery, and -2.52 μmol/L and -16.5%, respectively, in those with ventricular tachycardia. Conclusion The indexes of cerebral oxygenation may drop severely enough during maximal exercise in some patients with severe IDC that consciousness is affected. (Circ J 2006; 70: 1457 - 1461)
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  • Kohei Matsushita, Toshiyuki Ishikawa, Shinichi Sumita, Tsukasa Kobayas ...
    2006 Volume 70 Issue 11 Pages 1462-1465
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background Clinical data suggest that changes in intrathoracic impedance and fluid accumulation in the lung are inversely related. Methods and Results Daily shock impedance (S-IMP) was evaluated in 29 patients in whom a Ventak Prizm 2 was implanted (61±14 years old). The mean follow-up period was 45±18 weeks, during which 6 patients had episodes of decompensated heart failure (DHF group) and the others did not (NHF group). There was no significant difference between the DHF group and NHF group in the mean value of the S-IMP (46.4 ±3.3 vs 45.4±5.4 Ω). The range of S-IMP in individual patients in the DHF group was significantly greater than that in the NHF group (13.8±0.38 vs 7.0±3.1 Ω, p<0.0001). Mean weekly change of S-IMP in individual patients in the DHF group was significantly greater than that in the NHF group (1.583±0.630 vs 1.092±0.361 Ω, p<0.0176). When the cut-off value was set at >1.242 Ω, sensitivity was 100% and specificity was 69.6% for a diagnosis of DHF. There was a significant negative correlation between the percent increases in brain natriuretic peptide (BNP) and S-IMP (correlation coefficient: -0.775 p<0.0001) in the DHF group. There was an inverse relation between BNP and S-IMP. Conclusions Measurement of shock impedance may be useful in the management of congestive heart failure. (Circ J 2006; 70: 1462 - 1465)
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  • Akiyoshi Hashimoto, Tomoaki Nakata, Nagara Tamaki, Takeshi Kobayashi, ...
    2006 Volume 70 Issue 11 Pages 1466-1474
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background Impaired fatty acid metabolism the myocardial infarction (MI)-related area has prognostic value, but can alter over time. The aim of this study was to correlate alterations in myocardial fatty acid uptake and perfusion assessed by serial imaging with future outcomes in post-MI patients. Methods and Results Following 2 imaging procedures using 15-4-iodophenyl-3-(R,S)-methylpentadecanoic acid (BMIPP) and perfusion tracers at an 11-month interval, 97 patients with acute MI were followed up for 33 months with respect to the primary endpoints of death, non-fatal MI and heart failure. Regional tracer uptake was semi-quantified for both the MI-related and remote coronary territories. A large BMIPP defect relative to a perfusion defect appeared on MI-related coronary territories. Thirteen patients with cardiac events had a greater prevalence of large BMIPP and perfusion defect scores for the MI-related areas on the first scan, previous MI, diabetes mellitus, and worsening of perfusion tracer uptake in the MI-related area than those without cardiac events. Multivariate analysis identified worsening perfusion in the MI-related area on the second scan, a large BMIPP defect in the same area on the first scan and previous MI as significant predictors with chi-square values of 3.48, 6.41 and 6.84, respectively. A combination of 3 predictors significantly (p<0.05) increased the global chi-square value to 15.45 compared with each chi-square value. Conclusions The size of the infarct-related risk area assessed by early cardiac BMIPP imaging and deterioration of perfusion tracer uptake in the compromised area for the first 12 months following acute MI are related to future cardiac events, indicating a rationale for identifying metabolically damaged but viable myocardium for further risk stratification of post-MI patients. (Circ J 2006; 70: 1466 - 1474)
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  • Masaya Kato, Keigo Dote, Shota Sasaki, Kentaro Ueda, Kenji Goto, Hiroa ...
    2006 Volume 70 Issue 11 Pages 1475-1480
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background Coronary microcirculatory damage is an important factor for the prognosis for acute myocardial infarction (MI) after revascularization. The myocardial enhancement area with contrast media infused during coronary revascularization therapy, detected by computed tomography (CT) just after revascularization, has been reported to correspond to the area of hemorrhagic infarction. The relationship between myocardial contrast enhancement and coronary microcirculatory damage was investigated in the present study. Methods and Results Thirteen patients with acute anterior MI underwent successful coronary revascularization within 6 h of symptom onset were enrolled. The coronary flow velocity pattern was measured using a Doppler guidewire and chest CT assessments were performed immediately after coronary revascularization. The ratio of mean CT number of the highest-enhanced myocardial area and the lumen of the left ventricle was defined as a relative CT number. The relative CT number significantly correlated with coronary diastolic deceleration time (r=-0.78, p<0.002) and coronary diastolic deceleration rate (r=0.74, p<0.04). It also correlated with peak myocardial enzyme release in plasma. Conclusion Myocardial contrast enhancement detected using plain CT just after coronary reperfusion therapy implies coronary microcirculatory damage in acute MI. The relative CT number is useful in evaluating the impaired coronary microcirculatory state. (Circ J 2006; 70: 1475 - 1480)
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  • Kenichi Nakajima, Masaya Kawano, Minoru Hasegawa, Junichi Taki, Manabu ...
    2006 Volume 70 Issue 11 Pages 1481-1487
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background Cardiac involvement is an important factor for the appropriate management of systemic sclerosis (SSc). The possibility for detecting early myocardial damage was investigated using 99mTc methoxyisobutylisonitrile (MIBI) gated perfusion single photon emission computed tomography (SPECT) and 123I metaiodobenzylguanidine (MIBG) sympathetic imaging. Methods and Results Twenty-three patients with SSc and 14 control subjects were studied. The severity of SSc was defined by disease type and semi-quantitative skin thickness scores. A myocardial perfusion study was performed using 99mTc MIBI exercise - rest study, and systolic and diastolic parameters were calculated from the volume curve of the gated SPECT. 123I MIBG was evaluated by segmental defects, a heart-to-mediastinum ratio and washout rate (WR). No significant exercise-induced ischemia was observed and the left ventricular ejection fraction was within normal range in patients with SSc. However, diastolic function calculated by time to peak filling (TPF) in the early diastole was significantly prolonged in SSc compared with the control group (184±35 ms, 160±25 ms, p=0.030) and more rapid MIBG WR from the myocardium (18.2±7.0% vs 11.1±4.3%, p=0.0015). Compared with the control group, the severe group with either diffuse SSc or a skin thickness score ≥10 had more prolonged TPF/RR interval than the less severe group. Both diastolic and sympathetic abnormalities were observed in 7 (30%) patients, and 1 abnormality in 17 (74%) patients with SSc. Conclusions In patients with SSc, either diastolic dysfunction or sympathetic derangement, or both were observed even without induced ischemia and normal ventricular contractility. Based on these subclinical early findings, further follow-up studies are recommended. (Circ J 2006; 70: 1481 - 1487)
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Experimental Investigation
  • Koki Hoshiyama, Motoki Hara, Kenji Yasui, Hideo Mitamura, Fumitaka Ohs ...
    2006 Volume 70 Issue 11 Pages 1488-1496
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background Electrical instability following sustained rapid excitation has been attributed to altered ion channels. Alterations of Ca2+ handling could also contribute to abnormal dynamics of action potential, favoring the initiation and perpetuation of arrhythmia. Methods and Results Transmembrane action potentials and twitch force (TF) were recorded from normal (n=6) and remodeled (6-week atrial pacing at 400 beats/min, n=6) canine atria. When the cycle length (CL) was suddenly prolonged in normal atria, both TF and action potential duration (APD) increased on the first beat, and decreased subsequently. Opposite changes were observed with sudden CL shortening. These dynamics in both APD and TF were abolished by ryanodine, but augmented by cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum (SR) Ca2+ pump. In remodeled atria (RA), dynamic changes in APD were also concordant with dynamic changes in TF. The transient increases in APD and TF were enhanced, and the transient decreases were reduced compared to normal atria. The maximal slopes of APD and TF restitution curves were flatter and the magnitude of alternans was reduced in RA. The protein expression of SR Ca2+ ATPase and SR Ca2+-release channel in RA was significantly reduced. Conclusion Altered Ca2+ handling may underlie abnormal APD dynamics in RA. (Circ J 2006; 70: 1488 - 1496)
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  • Yosuke Kato, Mitsunori Iwase, Kenji Takagi, Takao Nishizawa, Hiroaki K ...
    2006 Volume 70 Issue 11 Pages 1497-1502
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background Although dilated cardiomyopathic hamsters (TO-2) with mutation of the δ-sarcoglycan gene exhibit histological features of muscular dystrophy, it remains to be elucidated whether both myocardium and skeletal muscle are injured in a similar manner. Methods and Results The progression of myolysis in both myocardium and skeletal muscle were assessed biochemically and pathologically in TO-2 and F1B control hamsters. Left ventricular (LV) function was assessed by echocardiography and cardiac catheterization. Both the plasma concentration of cardiac troponin T and the plasma activity of α-hydroxybutyrate dehydrogenase (HBD) peaked at 8 weeks of age, and thereafter reduced greatly in TO-2 hamsters. Activity of creatine kinase (CK) in TO-2 hamsters was significantly greater than in controls throughout the observation period. Pathological findings of both nuclear chain and central nuclei in skeletal muscles were observed in TO-2 hamsters throughout the observation period, suggesting regeneration. LV dysfunction was first evident at 8 weeks of age and deteriorated thereafter in TO-2 hamsters. Treatment of TO-2 hamsters with diltiazem from 5 to 8 weeks of age could avert the LV functional deterioration and the increment in α-HBD activity, but CK activity was unchanged. Conclusions Despite myolysis in skeletal muscle occurring consistently throughout the observation period, cardiac myolysis occurred predominantly in the early phase. These initial cardiac events might involve coronary spasm and/or calcium overload in the myocardium. (Circ J 2006; 70: 1497 - 1502)
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  • Makoto Yoshimitsu, Koji Higuchi, Fayez Dawood, Vanessa I. Rasaiah, Bil ...
    2006 Volume 70 Issue 11 Pages 1503-1508
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background Recombinant lentiviral vectors (LVs) offer the possibility of stable, long-term expression of transgenes even in non-dividing cells. In the present study this vector system was applied to a clinically relevant cardiovascular problem. Methods and Results Fabry disease results from deficient activity of α-galactosidase A (α-gal A) and cardiac abnormalities are a common and an important cause of death in patients with the disease. A therapeutic LV that delivers the α-gal A cDNA has been synthesized. In vitro studies established efficient transduction of the H9c2 rat cardiomyocytes and showed overexpression of enGFP (control) and α-gal A. In in vivo studies, the enGFP cDNA was transferred into C57BL/6 mouse hearts by direct intraventricular injection. Next, in a mouse model of Fabry disease, the recombinant therapeutic construct was delivered analogously. In cardiac tissue, α-gal A activity rose to 23% of normal levels at day 7 after LV injection, which is encouraging because levels of correction approximating 5% of normal may be curative for this disorder. There was also a corresponding reduction in globotriaosylceramide accumulation. Other organs assayed showed no detectable changes in α-gal A activity levels in injected animals. Conclusion A localized benefit of directly injecting a therapeutic LV into the heart has been shown, confirming the utility of this delivery system for research and therapy for a variety of cardiovascular disorders. (Circ J 2006; 70: 1503 - 1508)
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  • Norio Igarashi, Takashi Nozawa, Nozomu Fujii, Takayuki Suzuki, Akira M ...
    2006 Volume 70 Issue 11 Pages 1509-1514
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    Background Increases in sympathetic nerve activity during ischemia may increase intracellular fatty acid (FA) accumulation via enhanced FA uptake and inhibition of β-oxidation. Therefore, the beneficial effects of β-adrenoceptor blockade on myocardial ischemic injury might result from the suppression of FA accumulation. Methods and Results Carvedilol (1 mg/kg) or propranolol (1 mg/kg) was injected 10 min before 15-min occlusion of coronary artery in rats. Myocardial FA accumulation and intracellular metabolites of FA tracer were determined 3 days after reperfusion using 125I-and 131I-9-metylpentadecanoic acid (9MPA). Carvedilol significantly decreased 9MPA accumulation in both the ischemic region (IR) and non-IR, as compared with vehicle, and increased its clearance. However, the non-metabolized 9MPA fraction was not different between carvedilol- and vehicle-treated rats. Consequently, the amount of non-metabolized 9MPA in the myocardium was lower in rats treated with carvedilol than in those given vehicle. These effects of carvedilol were not different from those of propranolol. Conclusion Beta-adrenoceptor blockade did not affect a visual assessment of the autoradiographic image of 9MPA in hearts subjected to ischemia-reperfusion, but it accelerated the clearance of 9MPA in both the IR and non-IR. The administration of β-blockade before ischemia could accelerate the recovery from ischemia-reperfusion injury by inhibiting myocardial FA accumulation before β-oxidation. (Circ J 2006; 70: 1509 - 1514)
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Case Report
  • Takahiro Sawada, Junya Shite, Toshiro Shinke, Satoshi Watanabe, Hiroma ...
    2006 Volume 70 Issue 11 Pages 1515-1519
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    A 76-year-old man presented with an anterior myocardial infarction. Coronary angiography showed 99% stenosis in the left anterior descending artery and total occlusion in the left circumflex artery (LCX). After successful percutaneus coronary intervention (PCI) for segment 7, a staged PCI to the LCX with a distal protection system was attempted, but the wire entered the subintima, creating a large dissection and intramural hematoma. Three sirolimus-eluting stents (SES) were implanted to cover the entire hematoma, but 2 weeks later intravascular ultrasound revealed stent malapposition, with healing of the residual hematoma, and vessel enlargement. Optical coherence tomography (OCT) showed the malapposition more clearly. Balloon dilatation successfully achieved apposition of the SES to the vessel wall, but 6 months later it revealed recurrence of malapposition, with the struts covered by thrombus-like tissue. This case suggests that SES implantation treatment of a long intramural hematoma can potentially cause late malapposition because of persistent vessel enlargement related to arterial wall injury and inhibition of neointimal hyperplasia by the SES. OCT is useful in showing the precise condition of the stent struts. (Circ J 2006; 70: 1515 - 1519)
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  • Hangyuan Guo, Fang Peng, Takanori Ueda
    2006 Volume 70 Issue 11 Pages 1520-1522
    Published: 2006
    Released: October 25, 2006
    JOURNALS FREE ACCESS
    A case of a lost guide wire extending from the vena cava to the back of the neck after central venous catheterization is presented. A trainee inserted a central venous catheter via the left subclavian vein in a 40-year-old male patient after surgery, but did not notice that a guide wire was completely inserted in the vein. After 6 months, the lost guide wire was seen extending from the saphenous vein through the vena cava, right atrium, right ventricle, pulmonary artery and lung tissue to the back of neck. Although percutaneous catheterization of central veins is a routine technique, it is a procedure requiring advanced surgical skills, expert supervision, and attention to detail in order to prevent adverse effects. The present case is not only a technological problem, but also one of responsibility. The operator must hold onto the guide wire at all times until removal from the vessel, and a supervisor must make sure that trainees are aware of all possible complications. (Circ J 2006; 70: 1520 - 1522)
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