We estimated the benefit of a sirolimus-eluting stent (SES, Cypher ^®) for diffuse (> 10 mm) in-stent restenosis (ISR) inside bare metal stents (BMS) because the feasibility of the SES was not confirmed after its recent approval in Japan. Clinical and angiographic outcomes after SES implantation to 93 diffuse ISR were compared with those of 3 groups treated by plain old balloon angioplasty (POBA, (n = 54)), cutting balloon angioplasty (CB, (n = 24)), and BMS (n = 41) in a series of 153 patients whose follow-up quantitative coronary angiography (QCA) evaluated 3-9 months after the treatments was obtained from January 2003 through December 2005. For 33 lesions in the SES group, 12-month follow-up QCA results were obtained and compared with those at 6 months. Ticlopidine (200 mg/day) was prescribed for at least 12 weeks after SES implantation and for 2 weeks after BMS in addition to aspirin (81-100 mg/day). Patient characteristics and the characteristics of previous implanted BMS in the SES group were not significantly different from those in the other groups. Death from cardiac causes and nonfatal myocardial infarction did not occur in any group. Stent thrombosis was not observed in the BMS and SES groups. The incidence of repeat target lesion revascularization (re-TLR) in the SES group (3.23%) was significantly lower compared with that of the POBA (37.0%), CB (25.0%), and BMS (29.3%) groups (P < 0.001, respectively). Late loss in the SES group (0.44 ± 0.41 mm) was significantly smaller than that in the BMS group (1.34 ± 0.74 mm) (P < 0.05). The rate of recurrent ISR (re-ISR) in SES (5.38%) was significantly lower than that in POBA (46.3%), CB (41.7%), and BMS (46.3%) (P < 0.001, respectively). The QCA variables at 6 months in the SES group were not significantly different from those at 12 months. Thus, SES implantation for diffuse ISR was far superior since it markedly reduced the incidence of re-TLR with re-ISR at up to 6-months follow-up. In addition, this angiographic patency after SES implantation continued until 12 months.

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It is still controversial whether percutaneous coronary intervention (PCI) is effective in improving in-hospital survival in very elderly patients. Therefore, using data from the Tokai Acute Myocardial Infarction Study II, we studied the effect of emergency PCI on the in-hospital mortality of very elderly (80+ years of age) patients with acute myocardial infarction (AMI). The study was a prospective study of all consecutive patients admitted to the 15 acute care hospitals in the Tokai region with the diagnosis of AMI from 2001 to 2003. A total of 211 patients undergoing emergency PCI and 176 patients not undergoing PCI were included in the present analysis. We compared the baseline and procedural characteristics and the clinical outcomes between the 2 groups. Patients without emergency PCI were older and had an increased prevalence of female gender, ADL impairment, and dementia in comparison with those with PCI. They also showed poorer clinical conditions. They were less likely to be transferred to intensive care or coronary care units and to be given intra-aortic balloon pumps. The patients with emergency PCI had nearly one-third the in-hospital mortality rate of the patients without emergency PCI. According to multivariate analysis, emergency PCI was still identified as an independent predictor of in-hospital death, with an adjusted odds ratio of 0.26 (95% CI, 0.07-0.97). The results indicated that emergency PCI has a preventative effect on in-hospital mortality in Japanese AMI patients 80 years of age and older.

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Accumulating evidence suggests that higher antibody titers to heat shock proteins (HSPs) are associated with the development and severity of atherosclerosis. The aim of this study was to evaluate the impact of cardiac rehabilitation therapy (CRT) or stain treatment (STT) or a combination of both (COM) on anti-HSP antibodies in patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI). Clinical evaluation of subjects was performed both at the commencement and completion of the 14 weeks of treatment. CRT consisted of a supervised 6 weeks of exercise following hospital discharge and 8 weeks of home stay exercise. Patients assigned to statin therapy were treated with 80 mg per day of fluvastatin. Blood samples from 39 patients were analyzed for antibodies to HSP60 and HSP70 by ELISA. Biochemical parameters, including lipids, high-sensitivity C reactive protein (hsCRP), and interleukin-6 (IL-6), were also analyzed. We found that CRT and COM reduced antibody titers to HSP60 and HSP70 in CAD patients (by 3.79 and 10.00% of anti-HSP60, and by 5.74 and 3.45% of anti-HSP70, respectively) but statin treatment reduced only antibody titers to HSP70 (by 3.83%). There was a significant correlation between antibody titers to HSP60 versus HSP70. Considering the fact that antibody titers to HSPs are associated with the autoimmune process in CAD, CRT and COM have greater effects on reduction in autoimmune reaction after PCI than statin treatment. This reduction was accompanied by greater improvements in blood biochemical variables, such as lipids, hsCRP, and IL-6 after CRT and COM.

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Prior intravascular ultrasound (IVUS) studies have demonstrated that a positive remodeling pattern of a culprit lesion is observed more frequently in acute coronary syndrome (ACS) than stable angina (SA). However, the relationship between the plaque morphology detected by IVUS and the histological type of atherosclerotic plaque has not been well defined. This is a prospective study on 37 consecutive patients who underwent directional coronary atherectomy. The 37 patients were divided into 2 groups; 21 patients with SA and 16 with ACS. Vessel and plaque cross sectional area were measured at the culprit lesion and the remodeling index (RI) was calculated by IVUS. The plaque tissue was assessed for the presence of inflammatory cells and lipids, and the presence of each was scored as 0 (absent), 1 (sparse), 2 (dense), or 3 (predominant). The RI of the patients with ACS was higher than that of SA. Inflammatory cells were present to a greater extent in patients with ACS. Inflammatory cells and lipids were significantly correlated with the RI (Inflammatory cell score grade ≥ 2 patients; 1.14 ± 0.13 versus grade 0 patients; 0.87 ± 0.24, and grade 1 patients; 0.93 ± 0.17, P < 0.01 and lipid score grade ≥ 2 patients; 1.13 ± 0.17 versus grade 0 patients; 0.85 ± 0.18, P < 0.001 and grade 1 patients; 0.95 ± 0.19, P < 0.05). The results clearly indicate that the evaluation of vessel morphology by vascular imaging is an important indicator of plaque instability.

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A new controlled-release isosorbide-5-mononitrate (CR-ISMN) preparation has been developed to meet the requirement for a low nitrate concentration interval in order to avoid nitrate tolerance.
We conducted a randomized, double-blind, placebo-controlled study in 31 Japanese patients with stable effort angina pectoris to investigate the efficacy and safety of CR-ISMN. Patients were randomly assigned to either CR-ISMN (40 mg once daily) or placebo groups for 2 weeks after two consecutive symptom-limited treadmill exercise tests using the Bruce protocol to ascertain the reproducibility of exercise tolerance during the placebo run-in period. Exercise tests were repeated at 5, 12, and 24 hours after administration on the final day.
No significant difference in exercise time to moderate angina was identified between the CR-ISMN and placebo groups at 5, 12, or 24 hours after administration. However, the changes in exercise were prolonged at 5 hours but not shortened at 24 hours in the CR-ISMN group. The results of subgroup analysis suggested that the concomitant use of insulin might lead to confounding results. Although headache was the most frequent adverse effect in the CR-ISMN group, all symptoms were mild and at self-limiting levels. The plasma concentrations of CR-ISMN maintained therapeutic levels at 5 and 12 hours, and gradually decreased to less than the minimum therapeutic concentration (100 ng/mL) at 24 hours after administration.
This study demonstrates that CR-ISMN improves exercise tolerance during the daytime and is well-tolerated in Japanese patients with stable effort angina pectoris without increasing the number of serious adverse effects.

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Late angiographic stent thrombosis (LAST) in a drug-eluting stent has been reported in several studies. Most LAST occur just after discontinuation of antiplatelet therapy. We report the first case of LAST that occurred 21 months after implantation of a Cypher stent and 20 months after discontinuation of clopidogrel, results that suggest a mechanism other than the discontinuation of antiplatelet therapy might be responsible for LAST.

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Although angiotensin-converting enzyme inhibitors (ACEIs) have been shown to reduce left ventricular remodeling after acute myocardial infarction (AMI), the effects of angiotensin receptor blockers have yet to be established. This study was conducted to examine the effects of candesartan on left ventricular remodeling after AMI. Consecutive AMI patients were assigned to a candesartan group or ACEI group after successful coronary intervention. The patients in the candesartan group (n = 77, mean age, 62.8 ± 1.3) received candesartan and the patients in the ACEI group (n = 80, mean age, 63.3 ± 1.2) received lisinopril, enalapril, or trandolapril. Four mg was the most frequent dose in the candesartan group at 6 months. Lisinopril, enalapril, and trandolapril were administered to 52%, 27%, and 21% of the patients in the ACEI group, respectively. No significant differences in the incidences of cardiac death, nonfatal MI, or hospitalization for heart failure (P = NS) were found between the groups. The candesartan group exhibited a somewhat higher percent increase in left ventricular ejection fraction and significantly lower percent increases in left ventricular end-diastolic volume index and left ventricular end-systolic volume index compared to the ACEI group (P < 0.05, P < 0.05, respectively). Candesartan is more effective than ACEI in preventing left ventricular remodeling after AMI.

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Previous studies have reported that skeletal muscle strength is closely related to exercise capacity in patients with myocardial infarction (MI). However, none of the previous studies have fully investigated the correlation between exercise capacity and the skeletal muscle volume (MV). Seventy patients with MI underwent symptom-limited cardiopulmonary exercise testing using a treadmill. The MV was evaluated by electrical impedance analysis and the maximal knee extension strength (Peak torque: PT) was measured by a Biodex. The subjects were divided into 2 groups according to the MV (group L, MV < 22 kg; group H, MV ≥ 22 kg). The PT was positively and significantly correlated with the peak VO₂ in both the L and H groups (r = 0.70 versus r = 0.71). The MV of the lower limbs was positively correlated with the peak VO₂ in the L group (r = 0.57), but not in the H group. The lower limb MV was positively and significantly correlated with PT in the L group (r = 0.48), but not in the H group. The exercise capacity of patients with MI is thought to depend on both the strength and volume of the skeletal muscle. In MI patients with high muscle volume, exercise capacity was determined by skeletal muscle strength alone.

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Results from the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) study showed that clopidogrel plus aspirin, compared to aspirin alone, reduced cardiovascular events (death, myocardial infarction, and stroke) in patients with acute coronary syndromes (ACS). Yet the acquisition cost of clopidogrel is much higher. It would therefore be worthwhile to compare the long-term cost impact of these 2 regimens.
Until recently, only very few patients with ACS received clopidogrel-aspirin combination therapy in Hong Kong. Therefore, a hypothetical cohort was formed and compared to a real group of patients treated with aspirin alone. For the aspirin group, medical history was reviewed and cardiovascular and gastrointestinal events occurring in a period of 12 months after initiation of therapy were recorded. The target cost items included hospitalisation, emergency room visits, outpatient clinic visits, related medications, diagnostic tests, procedures, and surgery. For the hypothetical cohort, the probabilities/relative risks for clinical events were adopted from the CURE study.
Fifty-four consecutive patients with ACS receiving aspirin therapy were identified and studied between January 1, 2001 and December 31, 2001 from a major public hospital in Hong Kong. The average cost of management per patient over the 12 month period for the aspirin group was HK$85,324 (US$10,940, HK$7.8 = 1 US$) versus the hypothetical cohort HK$83,903 (US$10,757). Hospitalisation represented the major cost item (64.6%), followed by the cost of investigational tests (14.5%) and procedural cost (11.6%).
According to our analytical model, the overall cost impact between clopidogrel plus aspirin versus aspirin alone in the 2 groups of patients was similar.

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It is not yet clear whether a difference in in-hospital morality between patients with and without renal insufficiency undergoing percutaneous coronary intervention (PCI) exists. Therefore, the aim of the present study was to investigate if such as association exists in Japan. Data from the Tokai Acute Myocardial Infarction Study II were used. This was a prospective study of all 3274 patients admitted with acute myocardial infarction (AMI) to the 15 participating hospitals from 2001 to 2003. We abstracted the baseline and procedural characteristics as well as in-hospital mortality from detailed chart reviews. Patients were stratified into 2 groups according to the estimated creatinine clearance on admission. The creatinine clearance values were available in 2116, 107 of whom had renal insufficiency. The patients with renal insufficiency were more likely to be older, female, not independent in their daily activities, have lower body mass index and higher heart rate values on admission, lower prevalences of hypercholesterolemia and peptic ulcers, greater prevalences of diabetes, angina, previous heart failure, previous renal failure, previous cerebrovascular disease, aortic aneurysm, worse clinical course such as bleeding, and a multivessel coronary disease. Vasopressors, an intra-aortic balloon pump, and mechanical ventilation were frequently used in the patients with renal insufficiency, while thrombolytics were used less frequently. The patients with renal insufficiency had a higher in-hospital mortality rate than those without. Multivariate analysis identified renal insufficiency as an independent predictor of in-hospital death. The results suggest that renal insufficiency is an independent predictor of in-hospital death among AMI patients undergoing PCI.

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Low energy internal cardioversion (ICV) is a relatively new method. This report describes the long-term follow-up results of a prospective randomized comparison of low energy ICV and transthoracic cardioversion (TT CV) in patients with persistent atrial fibrillation (AF).
Fifty-two patients (mean age, 60.6 ± 10.1 years, 23 males) with persistent AF were randomly assigned to either TT (n = 26) or ICV (n = 26). The baseline characteristics of the 2 groups were similar. Transthoracic CV was performed under sedation with hand-held electrodes in the apex-anterior position and high energy (100-360 J) monophasic shocks. ICV was performed by a dedicated balloon-directed catheter utilizing truncated, biphasic shocks of low energy (1-15 J).
Sinus rhythm (SR) was restored in 24/26 (92%) patients in the ICV group and in 22/26 (85%) patients in the TT CV group (P > 0.05). Immediate recurrence of AF (IRAF), defined as reappearance of AF within 2 minutes of successful CV, occurred in 5 patients (21%) in the ICV group and in 1 patient (4.5%) in the TT group (P > 0.05). Successfully cardioverted patients in whom no IRAF occurred were followed-up for 18 months under both warfarin and Class 1 or 3 antiarrhythmic drugs, as guided by the current ACC/AHA/ESC Guidelines. The rate of SR at 1, 3, 6, 12, and 18 months of follow-up was not significantly different between the 2 groups, and in an intention-to-treat analysis at 18 months, SR was present in 6 patients (23%) in the ICV group and in 10 patients (38%) in the TT group (P > 0.05). The majority of AF recurrences occurred within a month of successful CV in both groups (8/12 [67%] in the TT group and 15/18 [83%] in the ICV group, P > 0.05). The mortality, thromboembolic, and bleeding complication rates were similar in the 2 groups.
In this prospective randomized comparison of TT and low energy ICV in patients with persistent AF, the 18-month rates of SR and major adverse clinical events were found to be similar.

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The implantable cardioverter defibrillator (ICD) has proved effective in preventing sudden death and decreasing mortality in randomised secondary prevention trials. Some nonrandomised studies have reported different incidences and predictors of appropriate ICD therapy in patients with idiopathic dilated cardiomyopathy (DCM). The antiarrhythmic and other medical therapies were different between the published studies and it was reported that not using beta-blockers was a predictor of appropriate ICD therapy. In the present study, we report on our long-term experience with ICD therapy in patients with DCM, the majority of whom were treated with beta-blockers and amiodarone.
The study population consisted of 25 patients with DCM who underwent initial transvenous ICD implantation between December 1995 and May 2005. Indications for ICD implantation were monomorphic sustained ventricular tachycardia (VT) in 16 patients (64%), cardiac arrest in 8 patients (32%), and syncope plus inducible VT in one patient. Twenty-four patients underwent an electrophysiologic study (EPS). In 18 patients, the ICDs were programmed to only shocks and in 7 patients an additional antitachycardia pacing program was performed. One patient was lost to follow-up and 24 patients were followed-up primarily in our ICD pacemaker outpatient clinic. Appropriate ICD therapy was defined as antitachycardia pacing therapy or shock for tachyarrhythmia determined by evaluation of the clinical information and by device diagnostics to be either ventricular fibrillation or ventricular tachycardia.
The mean follow-up was 39.29 ± 30.59 months after ICD implantation. At follow-up, 17 patients were using a beta-blocker and 16 patients amiodarone. Appropriate ICD therapy was observed in 14 patients (58%). The detected arrhythmias were VT in 12 patients, ventricular fibrillation (VF) in one, and VT and VF in one patient. The time to first ICD therapy was 15.93 ± 18.45 (range, 1-74) months. Using the Kaplan-Meier method, the percent survival free of appropriate ICD therapy was 82%, 72%, 66%, and 55% at 1, 2, 3, and 4 years follow-up, respectively. The clinical, echocardiographic, and electrophysiologic characteristics did not differ between those who did and did not receive appropriate ICD therapy. However, the mean QRS duration was significantly longer in patients who received appropriate ICD therapies. Cox regression analysis did not reveal any factors that predicted appropriate ICD therapy. Five patients (21%) died during follow-up. Four deaths were classified as cardiac and one as noncardiac. The cumulative survival from total death was 94%, 82%, 82%, and 69%, and the cumulative survival from cardiac death was 94%, 82%, 82%, and 76% during 1, 2, 3, and 4 years of follow-up, respectively.
In summary, in this selected patient population with DCM, the majority of patients were unresponsive to beta-blocker and antiarrhythmic therapy. Most of these patients received appropriate ICD therapy during follow-up. Cox regression analysis did not identify any factors that predicted appropriate ICD therapy. Additional trials with larger patient populations are needed to detect the predictors of appropriate ICD therapy in patients with DCM.

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Acute pulmonary embolism continues to cause significant morbidity and mortality despite advances in diagnosis and treatment. This retrospective analysis aimed to determine whether the combination of elevated troponin I and right ventricular dilatation (RVD) could provide a more powerful predictor for risk evaluation.
The study data comprised records of 110 patients with either high-probability ventilation/perfusion lung scan or positive spiral computed tomography. All cause 100-day mortality was 18.2%. The hypotension and RVD variables significantly influenced 100-day mortality. For the combination of RVD and raised troponin I, the 100-day mortality rate was 31%. Notably, the group with elevated troponin I and no RVD had a 100-day mortality rate of only 3.7%. The combination of RVD and elevated troponin had a positive predictive value of 31% and a negative predictive value of 88% for 100-day mortality. Compared with existing reports, conflicting conclusions for the individual prognostic role of elevated troponin I, cancer, and heart failure were obtained. These conflicting conclusions most likely resulted from inappropriate cut-off troponin I values and the modest sample size.
In conclusion, the combination of elevated troponin and RVD was able to identify a subset of patients most likely to benefit from aggressive therapy.

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Treatment with an angiotensin blocker (ARB) and an aldosterone blocker has been shown to have beneficial effects on cardiac remodeling in several cardiac diseases. It is still not clear whether the combination of these drugs is more effective against cardiac remodeling than the use of either agent alone. We examined the effects of combined treatment with valsartan, an ARB, and spironolactone, an aldosterone blocker, on cardiac remodeling in the renovascular hypertensive (RHT) rat. The RHT rats were divided into 4 groups administered valsartan (3 mg/kg/day, ARB group), spironolactone (4 mg/kg/day, SPRL group), both drugs at these doses (combined group), or neither drug (untreated RHT group). After 5 weeks, systolic blood pressure was significantly reduced in the 3 treatment groups, however, there were no significant differences in the extent of blood pressure reduction among the 3 treatment groups. The heart weight/body weight ratio in each of the 3 treatment groups was significantly lower than that in the untreated RHT group. The degree of cardiac and perivascular fibrosis in the SPRL group and the combined group were significantly lower than that in the untreated RHT group. Myocyte remodeling in the ARB group and in the combined group was significantly smaller than that in the untreated RHT group. These results suggest that SPRL treatment prevents cardiac and perivascular fibrosis and ARB treatment suppresses the cellular hypertrophy of myocytes, and that, therefore, combined treatment with both drugs prevents cardiac remodeling by acting against both myocyte hypertrophy and cardiac fibrosis in RHT rats.

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A 37 year-old female who had suffered from arteritis for 20 years underwent a Bentall operation. Since severe stenosis was observed in her left main coronary artery (LMCA) the following year, a minimally invasive direct coronary artery bypass (MIDCAB) operation was performed. Unfortunately, she again complained of angina about 6 months after the second surgery and coronary angiography (CAG) revealed that her left internal thoracic artery graft was totally occluded. Although a 4.0 × 15 mm S670 stent was placed in her LMCA, the LMCA restenosed every 3 months and she underwent reintervention 8 times. We placed 2 sirolimus-eluting stents for treating the LMCA using the culottes stenting technique. CAG 6 months after the index procedure showed no stenosis at her LMCA. Sirolimus-eluting stents were effective for treating stenosis resulting from arteritis as well as that caused by atherosclerosis.

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Cardiac pacemakers and implantable defibrillators are commonly used therapeutic modalities in cardiac arrhythmias. Thalamic deep brain stimulation has also become an important modality in the treatment of drug-refractory tremors and other complications in advanced Parkinson's disease. Concerns exist about the potential electrical interaction and interference between these 2 devices in the same patient. There are only a limited number of reports that have investigated this issue. We describe a patient with advanced Parkinson's disease and a previously implanted deep brain stimulator, who subsequently needed a permanent cardiac pacemaker due to severe bradyarrhythmia. Despite the probability of interference between the devices, there were no problems during implantation of the cardiac pacemaker; both the deep brain stimulator and cardiac pacemaker functioned appropriately afterwards.

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