Background Until now, large-scale nationwide surveys of acute myocardial infarction (AMI), such as those performed in Europe and America, have not been performed in Japan. Therefore, in 2000 the Japanese Coronary Intervention Study (JCIS) group conducted a nationwide survey on the incidence of AMI in Japan. Methods and Results Questionnaires were collected from 8,268 facilities throughout Japan. The total annual number of patients with AMI was 66,459 (52.4 patients/10⁵ population), and the AMI incidence rate in Japan was approximately 25% of that in the United States. Most facilities with AMI patients treated less than 50 AMI patients annually, and that number was 45.0% of total AMI patients. The incidence of AMI patients was highest in Kochi, Kumamoto, and Wakayama prefectures, and lowest in Yamanashi, Saitama and Shiga prefectures. The ratio of the highest incidence to the lowest incidence was 2.0. A significant correlation was observed between the mean age of the prefectural population, as a coronary risk factor, and the incidence of AMI. Conclusions The incidence of AMI in Japan is approximately 25% that in the United States and it varies considerably among the prefectures, one of the causes being the difference in the mean age. This provides important information for assessing the guidelines for Japanese patients with AMI. (Circ J 2004; 68: 515 - 519)

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Background The association between myocardial infarction (MI) and the R353Q polymorphism of the Factor VII (FVII) gene, which reportedly influences FVII concentrations, activated Factor VII (FVIIa), or FVII antigen (FVIIag), remains controversial. Methods and Results The present case - control study in 127 Japanese men with their first MI at or before 45 years of age and 150 matched healthy controls was designed to clarify this association in premature MI. R353Q polymorphism was determined by polymerase chain reaction, and plasma concentrations of FVIIa and FVIIag were assayed. The distribution of the RR, RQ, and QQ genotypes with respect to R353Q polymorphism was 117, 10, and 0 in the patients, and 131, 17, and 2 in the controls. The Q allele was negatively associated with premature MI (odds ratio =0.41, p=0.038). The plasma concentration of FVIIa was slightly higher in patients (55.1±40.9 U/L) than in controls (44.8±20.2 U/L), but not significantly (p=0.078); the plasma concentration of FVIIag did not differ between patients (88.7±15.7%) and controls (87.0±9.0%) (p=0.557). Plasma FVIIa concentrations were influenced by R353Q polymorphism (p<0.001). Conclusions The Q allele may be protective against premature MI. (Circ J 2004; 68: 520 - 525)

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Background The clinical significance of the white blood cell (WBC) count on admission in relation to the duration of ischemia in acute myocardial infarction (AMI) remains unclear. Methods and Results The relationship of the WBC count on admission to myocardial reperfusion was examined in 135 patients with recanalization of an anterior AMI within 6 h of symptom onset. Patients were classified according to the WBC count on admission: Group L (n=75), WBC count <12,000 cells/mm³ and group H (n=60), WBC count ≥12,000 cells/mm³. Peak creatine kinase (CK) was higher and impaired myocardial reperfusion, defined as a myocardial blush grade of 0/1, was more frequent in group H than in group L. Among the patients in group H, those with early (≤3 h) recanalization had a lower QRS score before recanalization than those with late (>3 h) recanalization; however, peak CK and the incidence of impaired myocardial reperfusion were similar in these subgroups of patients. Multivariate analysis showed that WBC count ≥12,000 cells/mm³ on admission was an independent predictor of impaired myocardial reperfusion in patients with early recanalization (odds ratio 7.9, p=0.04), but not in those with late recanalization. Conclusions A higher WBC count may be associated with progression of myocardial damage after recanalization in patients with early recanalization of an anterior AMI. (Circ J 2004; 68: 526 - 531)

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Background Intracoronary radiation therapy (IRT) prevents recurrent in-stent restenosis, but its long-term safety and efficacy remain uncertain. In the present study, the long-term clinical outcome of IRT using the rhenium-188 (¹⁸⁸Re)-filled balloon system was evaluated. Methods and Results After successful catheter-based treatment of either a de novo or restenotic lesion, 187 patients were randomly assigned to either the radiation (N=104) or the control (N=83) group. The ¹⁸⁸Re-filled balloon system was designed to deliver 17.6 Gy to 1.0-mm tissue depth. Angiographic restenosis was significantly reduced with IRT at 9 months (18.9% vs 45.9%, p<0.001), but the incidence of major adverse cardiac events (MACE) including death, myocardial infarction, and target-vessel revascularization (TVR) by 3 years showed no difference. Lack of clinical benefit might be related to TVR caused by geographic miss (6/22, 28.6%), balloon-induced unhealed dissection (3/22, 13.6%) and late thrombosis (2/22, 9.1%). In the restenotic subgroup (N=39), the MACE rate within 3 years was significantly reduced with IRT (14.3% vs 54.5%, p=0.01). Conclusions IRT using the ¹⁸⁸Re -filled balloon system is safe and technically feasible. Although IRT failed to show favorable outcomes for de novo lesion, the clinical benefits for restenotic lesions seem durable for 3 years. Furthermore, preventing geographic miss and dissection might improve long-term outcomes. (Circ J 2004; 68: 532 - 537)

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Background There is a significant relationship between calcification of the aortic arch (Arch) detected by chest X-ray examination and coronary artery disease (CAD), but the relationship between risk factors, CAD and aortic calcification detected during a mass screening program using a mobile helical computed tomography (CT) unit remains unknown. Methods and Results In total 2,623 subjects (1,347 men, and 1,276 women; mean age, 52.9±13.8) underwent an examination for lung cancer and tuberculosis using a mobile helical CT unit. The frequency of calcification was 19.6% in the Arch, 2.7% in the ascending aorta, and 10.1% in the descending aorta, values that were positively associated with age in both genders. Hypertension and smoking were significantly related to calcification of the thoracic aorta. There was a significant relationship between CAD and aortic calcification. The odds ratio of aortic calcification for patients with CAD increased as the number of calcified segments increased. Conclusions These results suggest that detection of calcification in the thoracic aorta during a mass chest screening using a mobile helical CT unit can be used to evaluate the risk of CAD. (Circ J 2004; 68: 538 - 541)

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Background Oxidative stress may play an important role in the genesis and development of atherosclerosis. Methods and Results To examine whether oxidative stress is increased in the presence of various coronary risk factors, serum α-tocopherol concentrations were determined in 168 apparently healthy subjects recruited from Daioh town (73 men and 95 women, mean age: 42±11 years). The α-tocopherol concentration (mg/g lipids) was significantly lower in men, older subjects (≥50 years of age), smokers, those with hyper-low density lipoprotein (LDL)-cholesterolemia (C) (≥160 mg/dl), hypertriglyceridemia (TG) (≥150 mg/dl), hypo-high density lipoprotein (HDL)-C (<40 mg/dl), fasting hyperglycemia (>110 mg/dl) and obesity (body mass index ≥25 kg/m ²) than in women, younger subjects, nonsmokers, those with normoLDL-C, normoTG, normoHDL-C, fasting normoglycemia and the non-obese. The concentration was not significantly different between hypertensives and nonhypertensives. Multivariate logistic regression analysis showed that the adjusted odds ratios (95% confidence interval) for hyperTG and hypoHDL-C as a factor for the lowest tertile of α-tocopherol concentration were 6.2 (1.6-24.4, p<0.01) and 6.0 (1.5-22.6, p<0.01), and those of the other risk factors were not significant. The α-tocopherol concentrations were significantly positively correlated with HDL-C concentrations (R=0.53) and negatively with TG concentrations (R=-0.53), BMI (R=-0.35), LDL-C concentrations (R=-0.25) and age (R=-0.22). Conclusion Increased oxidative stress, as shown by decreased α-tocopherol concentrations, was linked to the presence of various coronary risk factors, among which hyperTG and hypoHDL-C appeared to be most heavily associated with oxidative stress. (Circ J 2004; 68: 542 - 546)

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Background Basic and clinical studies have indicated that 15-(p-[¹²³I] iodophenyl)-3-(R, S) methylpentadecanoic acid (BMIPP) single photon emission computed tomography (SPECT) can identify ischemic myocardium without evidence of myocardial infarction by the regional decline of tracer uptake. The present study compared BMIPP SPECT with rest-stress myocardial perfusion imaging (MPI) findings and coronary angiography (CAG) in 150 patients with acute chest pain. Methods and Results Patients with acute chest pain who underwent all of the following tests were selected: MPI at rest-stress, BMIPP SPECT at rest and CAG. Organic coronary artery stenosis (≥75%) was observed in 46 patients, 27 patients had total or subtotal coronary occlusion by spasm in the spasm provocation test on CAG and the remaining 77 patients had no significant coronary artery stenosis or spasm. The sensitivity of BMIPP at rest to detect organic stenosis was significantly higher (54%) than that of rest-MPI (33%, p<0.005), but lower than that of stress-MPI (76%, p=0.05). The sensitivity of BMIPP at rest to detect spasm was significantly higher (63%) than that of both rest-MPI (15%; p<0.001) and stress-MPI (19%; p<0.001). Overall, the sensitivity of BMIPP at rest to detect both organic stenosis and spasm was significantly higher (58%) than that of rest-MPI (26%; p<0.001), despite having no significance with that of stress-MPI (55%). The specificity was not significantly different among the three imaging techniques. Conclusion Resting BMIPP SPECT is an alternative method to stress MPI for identifying patients with not only organic stenosis but also spasm without the need for a stress examination. (Circ J 2004; 68: 547 - 552)

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Background Thoracic aortic injury resulting from blunt trauma is usually fatal and almost always associated with multiple, complex, nonaortic injuries that can adversely affect standard surgical repair of the aorta. Endovascular stent - graft treatment offers these patients a less invasive operative treatment option. Methods and Results Between January 2002 and October 2003, 6 patients with blunt aortic injury (BAI) were treated with a stent - graft. In all cases endovascular management was selected because of associated polytrauma or comorbidities. All stent - grafts were homemade and deployed through the femoral artery with 18-20 Fr delivery sheaths. There were no cases of perioperative death, renal failure, or neurologic complication. In one patient the postoperative computed tomography scan showed proximal endoleak requiring additional balloon dilatation and stenting. No other endoleaks were observed by CT in the acute phase. None of the follow-up CT scans revealed evidence of endoleak, migration, or alteration of the stent - graft. Conclusions Endovascular repair for BAI is technically feasible and is an alternative to open surgery for high-risk patients. (Circ J 2004; 68: 553 - 557)

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Background Even after successful slow pathway (SP) ablation for atrioventricular-nodal reentrant tachycardia (AVNRT), there may be clinical recurrence in certain patients and it is clinically important to be able to predict that. Methods and Results In 97 patients with common type AVNRT, the effective refractory period (ERP) of the fast pathway (FP), SP-ERP, and prolongation of the atrio-His (AH) interval (AH) at the time of jump-up phenomenon were investigated. In patients with residual SP, parameters were re-evaluated in a similar manner. SP was successfully ablated and AVNRT was not inducible in all the patients, but residual SP was observed in 54 of the 97 patients, and there was late clinical recurrence in 10 patients (10/54 patients with residual SP and 0/43 without residual SP, p=0.002). The changes in FP-ERP before and after ablation (ΔFP-ERP) did not differ between recurrent and non-recurrent patients. Among the patients with residual SP, ΔSP-ERP did not differ between the groups. However, the changes in ΔAH before and after ablation (ΔΔAH) were larger in non-recurrent (24±30 ms) than in the recurrent patients (4±7 ms, p=0.042). Conclusions In patients with AVNRT, the residual SP and changes in ΔAH after successful SP ablation might be useful indices of clinical recurrence. (Circ J 2004; 68: 558 - 562)

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Background The relationship between annual changes in blood pressure (BP) and the electrocardiogram (ECG) was studied to clarity what factors give early detection of complications and predict the outcome of therapy. Methods and Results The influence of BP on the ECG was assessed in 830 Japanese office workers. Those with hypertension (HT) more frequently developed left atrial and ventricular overload compared with normotensive subjects. In addition, those with borderline HT (systolic pressure 140-160 mmHg and/or diastolic pressure 90-95 mmHg) and even those with lower blood pressure (systolic pressure 130-140 mmHg and/or diastolic pressure 85-90 mmHg) developed left atrial and ventricular overload more frequently than normotensive subjects. Conclusions Based on these results, BP should be closely followed up when routine systolic and diastolic pressure levels exceed 130 mmHg and 85 mmHg, respectively, in persons in their 40 s to 50 s and the goal of antihypertensive therapy should be lower than reported previously. (Circ J 2004; 68: 563 - 567)

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Background Atrial fibrillation (AF) is believed to occur first as paroxysmal, then be gradually perpetuated, and finally become chronic as the end result. However, this presumed clinical course has not been well confirmed. Methods and Results The clinical course of recurrent paroxysmal AF (PAF) from its onset was examined in 171 patients (mean follow-up period: 14.1±8.1 years). This study population consisted of patients with no structural heart disease (n=88), ischemic heart disease (n=28), dilated or hypertrophic cardiomyopathy (n=17), valvular heart disease (n=35) or other cardiac diseases. The mean age at the onset of AF was 58.3 ±11.8 years old. During the mean follow-up period of 14.1 years, PAF eventually developed into its chronic form in 132 patients under conventional antiarrhythmic therapy (77.2%, 5.5% of patients per year). The independent factors for early development into chronic AF were aging (hazard ratio (HR) 1.27 per 10 years, 95% confidence interval (CI) 1.06-1.47)), dilated left atrium (HR 1.39 per 10 mm, 95% CI 1.11-1.69), myocardial infarction (HR 2.33, 95% CI 1.13-4.81), and valvular diseases (HR 2.29, 95% CI 1.22-4.30). Conclusions The present long-term observations definitely and quantitatively revealed the progressive nature of PAF. (Circ J 2004; 68: 568 - 572)

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Background It has been suspected for some time that patients with chronic heart failure (CHF) have abnormal muscle metabolism, so in the present study the muscle metabolism of the arm and leg were compared by ³¹P magnetic resonance spectroscopy (³¹P-MRS) to examine the relationship to exercise tolerance. Methods and Results The study group comprised 13 patients and 11 normal controls. Calf-plantar and forearm-wrist flexion were performed to evaluate the metabolic capacity assessed as the phosphocreatine breakdown rate (PCr-slope) and muscle pH at a submaximal (70% peak) work rate (submax-pH). Exercise of both the arm and leg resulted in an earlier decrease in PCr and muscle pH in patients with CHF compared with controls. There were significant correlations between peak oxygen uptake (peak V_O2) and the PCr-slope in both limbs in patients with CHF (forearm: r=0.63, p<0.05; calf: r=0.60, p<0.05), but no correlations in normal controls. There was a close correlation between the ventilatory anaerobic threshold (AT) and the PCr-slope in the calf (r=0.85, p<0.01), but not in the forearm in patients with CHF. Submax-pH in both upper and lower limbs was not significantly correlated to peak V_O2 or AT in either patients with CHF or controls. Conclusions Although metabolic abnormalities during exercise are seen in both arms and legs, leg muscle abnormalities, in particular, are closely related to systemic exercise intolerance in patients with CHF. (Circ J 2004; 68: 573 - 579)

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Background Myocardial infarction (MI) promotes deleterious remodeling of the myocardium, resulting in ventricular dilation and pump dysfunction. Supplementing infarcted myocardium with neonatal myocyte would attenuate deleterious remodeling and so the present study used Doppler echocardiography and histology to analyze the cardiac function and histological regeneration of the damaged myocardium after cellular cardiomyoplasty. Methods and Results Experimental MI was induced by 24-h coronary ligation followed by reperfusion in adult male Lewis rats and neonatal myocytes were injected directly into the infarct and peri-infarct regions. Three groups of animals were studied at 4 weeks after cellular cardiomyoplasty: noninfarcted control (control), MI plus sham injection (MI), and MI plus cell injection (MI + cell). Ventricular remodeling and cardiac performance were assessed by Doppler echocardiography or contrast echocardiography. At 4 weeks after cellular cardiomyoplasty, MI + cell hearts exhibited attenuation of global ventricular dilation and cardiac function compared with MI hearts not receiving cellular cardiomyoplasty. Immunohistochemically, connexin-43-positive small cells were observed in the vicinity of the infarction in MI + cell heart. By electron microscopy, these cells contained myofilaments with Z-bands and poorly developed intercalated disks, suggesting neonatal myocardial cells. Furthermore, the myocardial cells were often making close contact with interstitial cells. Conclusions Implanted neonatal myocytes form viable grafts after MI, resulting in attenuated ventricular dilation and enhanced contractile function. Echocardiography, electron microscopy, and immunohistochemistry are useful methods for assessing the functional and histological regeneration of the damaged myocardium. (Circ J 2004; 68: 580 - 586)

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A patient with idiopathic long QT syndrome had repeated syncopal episodes. The QTc interval on the electrocardiogram at rest was 530 ms and was prolonged by exercise up to 740 ms with T wave alternation. Intravenous epinephrine (0.1 μg/kg weight per min), but not isoproterenol (0.7 μg/min), produced early afterdepolarization of the monophasic action potential recorded at the right ventricular apex. Epinephrine prolonged the QTc interval to 710 ms. After the addition of propranolol to the epinephrine, the QTc (580 ms) was longer than at baseline. Methoxamine also prolonged the QTc to 580 ms. The QT interval in long QT syndrome is generally considered to be prolonged by a β-adrenergic effect, but in the present case α-adrenergic stimulation had an additional effect on the prolongation of the QT interval. (Circ J 2004; 68: 587 - 591)

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Primary pulmonary hypertension (PPH), which results from occlusion of small pulmonary arteries, is a devastating condition. Mutations of the bone morphogenetic protein receptor type II gene (BMPR2), a component of the transforming growth factor- β (TGF-β) family, which plays a key role in cell growth, have recently been identified as causing familial and sporadic PPH. The first case of BMPR2 mutation found in Japan is reported here in a 19-year-old woman with a clinical diagnosis of PPH and no identifiable family history of pulmonary hypertension. Direct sequencing of the entire coding region and intron/exon boundaries of BMPR2 revealed a frameshift mutation predicted to alter the cell signaling response to specific ligands. A molecular classification of PPH, based upon the presence or absence of BMPR2 mutations, might have important implications for patient management and screening of relatives. (Circ J 2004; 68: 592 - 594)

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Churg-Strauss syndrome is characterized by asthma, eosinophilia and systemic necrotizing vasculitis; cardiac involvement (ie, eosinophilic heart disease) is the major cause of morbidity and mortality, although there are no reports of an association between left ventricular dysfunction because of eosinophilic heart disease and myocardial blood flow or myocardial fatty acid metabolism. A patient presented with Churg-Strauss syndrome associated with eosinophilic heart disease that had progressed to dilated cardiomyopathy. Coronary angiography, thallium-201 (²⁰¹Tl) and iodine-123 β-methyl-iodophenyl pentadecanoic acid (¹²³I BMIPP) myocardial single photon emission computed tomography (SPECT) were performed to evaluate left ventricular dysfunction. Although coronary angiography was normal and ²⁰¹Tl SPECT showed no apparent image defect, ¹²³I BMIPP SPECT showed diffuse decreased accumulation, excepting the apex. The left ventricular dysfunction in patients with eosinophilic heart disease is associated with impaired myocardial fatty acid metabolism rather than with impaired myocardial blood flow. (Circ J 2004; 68: 595 - 598)

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A 63-year-old woman complained of chest pain and was referred to hospital where she was found to have left pleural effusion and swelling, local heat and edema of the right lower leg. Initial pulmonary perfusion scintigraphy demonstrated multiple defects and pulmonary thromboembolism (PTE) was confirmed during the anticoagulant and thrombolytic therapy against thrombophlebitis. A Greenfield filter was inserted in the inferior vena cava to prevent recurrence of PTE from the thrombosis that was resistant to therapy. In-111-labeled platelet scintigraphy (platelet scintigraphy) showed abnormal uptake of platelets in the chest, femoral veins and abdomen, which suggested active thrombus formation in those regions, including the filter, and a risk of recurrent PTE. Therefore, the thrombolytic therapy was terminated and the anticoagulant therapy intensified. A computed tomography (CT) scan revealed thrombus at the filter, which was markedly decreased 1 month later on platelet scintigraphy. Pulmonary ventilation and perfusion scintigraphy revealed remarkable improvement of the PTE. In this case, platelet scintigraphy complemented CT in demonstrating the activity and localization of the thrombus and can be used to evaluate the risk of recurrence during thrombolytic therapy after insertion of a filter. (Circ J 2004; 68: 599 - 601)

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Wrong:ichihara@higashi.hosp.jp
Right:ichihara@higashi-hosp.jp

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