The Vaughan Williams classification has been used widely by clinicians, cardiologists and researchers engaged in antiarrhythmic drug development and testing in many countries throughout the world since its initial proposal in the early 1970s. However, a major criticism of the Vaughan Williams system arose from the extent to which the categorization of drugs into classes I-IV led to oversimplified views of both shared and divergent actions. The Sicilian Gambit proposed a two-dimensional tabular framework for display of drug actions to solve these problems. From April to December 1996, members of the Guideline Committee met to discuss pharmacologic profiles of 4 antiarrhythmic drugs (aprindine, cibenzoline, pilsicainide, and pirmenol) that were not included in the original spreadsheet but are used widely in clinical practice in Japan. The discussion aimed to fit the drug profiles into the Gambit framework based on all the important literature published to date regarding the actions of the 4 drugs. This report is a summary of that deliberation. (Jpn Circ J 1999; 63: 1 - 12)

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The efficacy of intracoronary thrombolysis (ICT) for unstable angina pectoris (UAP) has been limited, despite the similar pathogenesis between UAP and acute myocardial infarction. To ascertain the subset of UAP suitable for ICT, the clinical responses to ICT were assessed in patients with UAP. Eighty-2 patients with medically refractory angina were divided into 2 groups according to the coronary artery morphology of the culprit lesion before ICT: (1) lesions with acute cut off and/or filling defects (AC) and (2) lesions with a tapered shape (TA). The TIMI flow grade was determined from coronary angiograms before and immediately after ICT. The diameter stenosis (%DS) and minimal lumen diameter (MLD) of the culprit lesion were determined using quantitative coronary angiographic analysis before and immediately after ICT. In addition, inhospital cardiac event rates including urgent / emergency coronary angioplasty or bypass surgery, nonfatal myocardial infarction or cardiac death were compared between the 2 groups. Multivariate logistic regression analysis was performed using 13 clinical factors contributing to successful ICT. The results showed that all 3 coronary angiographic parameters (TIMI flow, %DS, and MLD) significantly improved in the AC group (p<0.01, p<0.01 and p<0.05, respectively), whereas none of these parameters improved in the TA group. The inhospital cardiac event rate after ICT was significantly higher in the TA group (76%) than in the AC group (48%; p=0.016). Odds ratio predicting successful ICT was 7.09 (p<0.01) for the AC lesion, and 2.54 (p<0.01) for new angina. In conclusion the AC lesions are more commonly associated with coronary thrombosis that responds to ICT than are the TA lesions. Thus, the coronary angiographic morphology may be an important predictor for a successful ICT in patients with medically refractory UAP. (Jpn Circ J 1999; 63: 13 - 18)

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Adhesion molecules on the endothelial cell membrane play an important role in the pathogenesis of atherosclerosis. Levels of soluble forms of cell adhesion molecules are reportedly elevated in patients with peripheral artery vessel disease and in patients with an atherosclerotic aorta. The present study investigated the association of serum levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), and soluble P-selectin (sP-selectin) with coronary heart disease (CHD) and the extent of coronary atherosclerosis, and examined the influence of serum levels of lipids, lipoproteins and apolipoproteins (apo) in subjects with (n=52, M/F: 43/9) and without (controls, n=40, M/F:25/15) angiographically proven coronary atherosclerosis. After controlling for age and gender, levels of sVCAM-1 (least squares mean ± std error: 565±36 ng/ml vs 540±41 ng/ml, ns), sICAM-1 (261±17 ng/ml vs 247±19 ng/ml, ns), and sP-selectin (142 ±8 ng/ml vs 149±10 ng/ml, ns) in patients with coronary atherosclerosis were not different from those in controls, as assessed by an analysis of covariance. After also adjusting for body mass index, hypertension, diabetes mellitus, and smoking by a multiple logistic function analysis, the association of sVCAM-1, sICAM-1, and sP-selectin with CHD was still not significant. Levels of sVCAM-1, sICAM-1, and sP-selectin were also not related to the extent of coronary atherosclerosis as judged by the number of stenosed vessels. However, inverse (p<0.05) relationships were observed between sVCAMs and serum levels of HDL₃-cholesterol, apo A-II, and lipoprotein containing apo A-I and A-II, between sICAMs and levels of apo A-II and Lp A-I/A-II (Lp A-I/A-II), and between sP-selectin and lipoprotein containing only apo A-I. In conclusion, serum levels of soluble VCAM-1, ICAM-1, and P-selectin were not related to CHD or the extent of coronary atherosclerosis, but were inversely related to serum levels of high-density lipoprotein-related lipoproteins. (Jpn Circ J 1999; 63: 19 - 24)

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In order to investigate whether increased fine, fractionated signals within the QRS complex can detect arrhythmogenic substrates and how these fine signals link with ventricular mechanical dysfunction, wavelet analysis was performed on averaged QRS complexes obtained from the left precordial lead in 26 patients with idiopatic dilated cardiomyopathy (IDCM) and in 12 normal subjects. The number of local maxima and the duration of the wavelet transform were significantly greater in patients with IDCM than in normal subjects; the number at 100 Hz was 8.8±3.1 vs 6.0±1.1 (p<0.01), and the duration at 100 Hz was 93±15 vs 75±7 ms (p<0.01). Both of these indices were greater in the patients with than in those without late potentials, repetitive ventricular premature beats or cardiac death. In addition, significant inverse curvilinear relationships were observed between the left ventricular ejection fraction and both the number of local maxima and the duration of the wavelet transform. In conclusion, fine fragmented signals in the QRS complex detected by wavelet analysis would be an important marker for potentially arrhythmogenic substrates and seemed to progress in parallel with left ventricular mechanical dysfunction in IDCM. (Jpn Circ J 1999; 63: 25 - 32)

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This study evaluated the long-term prognosis of optimal `stent-like' results, suboptimal results and failure of balloon angioplasty. The clinical data of 108 patients were examined during 8 years following balloon angioplasty. Based on the angiographic results, the patients were divided into 3 groups: Group A (n=59), <25% residual stenosis (ie, optimal stent-like result); Group B (n=43), 26-50% residual stenosis or large dissection (ie, suboptimal result); and Group C (n=6), >50% residual stenosis or stenosis could not be crossed (ie, failed angioplasty). Restenosis occurred in 20 of 43 patients (46.5%) in Group B, but only in 18 of 59 patients (30.4%) in Group A. Achieving stent-like results following balloon angioplasty significantly reduced the incidence of restenosis. Kaplan-Meier curves at 8 years demonstrated a survival rate without serious cardiac events of 83% in patients with stent-like results compared with 58% in those with suboptimal results and 17% in those with failed balloon angioplasty. In conclusion, the major finding of this study is that achieving stent-like results following balloon angioplasty reduces the incidence of restenosis, and 8-year survival without serious cardiac events after balloon angioplasty is significantly better in patients who have a stent-like result. (Jpn Circ J 1999; 63: 33 - 36)

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Sudden unexpected death is generally considered to be caused by acute myocardial infarction and/or arrhythmia. To document the incidence and causes of sudden death in Japan, where the incidence of myocardial infarction is low, the present study examined death certificates, hospital records, the forensic medical records, and the police records of residents of the southern part of Okinawa island who died at the age of 20-74 years during a 3-year period from January 1, 1992 to December 31, 1994. Sudden death was defined as death within 24 h from the onset of unexpected symptoms. The study documented 126 (87 men and 39 women) sudden deaths. The crude incidence rate was 0.37/1,000 person per year (0.51 in men and 0.23 in women). According to the death certificates, 78 cases died of heart diseases. However, the cause of death could be determined by examination of all available records in only 64 cases: myocardial infarction in 10, non-ischemic heart diseases in 13, and stroke in 23 cases. Even when the analysis was limited to the cases who died within 1 h from the onset of symptoms, heart disease was the cause of death in only 22% of the cases while the cause of death could not be determined in 53% of the cases. Only 13% of those diagnosed as heart diseases on the death certificate were verified. The agreement rate between the diagnosis reached by the re-evaluation of the records and that on the death certificate was 82% for stroke and 33% for other diseases. In Okinawa, Japan, the frequencies of heart disease and stroke as the cause of sudden death may be similar. Except for stroke, the diagnosis appearing on the death certificate has substantial inaccuracy. (Jpn Circ J 1999; 63: 37 - 42)

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Although the mechanism of atrial fibrillation (AF) is still controversial, multiple wandering reentry is considered the primary mechanism in most AF. It has been suggested that prolongation of the wavelength would make it impossible for the reentry to continue and would lead to the termination of the AF. In the present study a dynamic fluctuation in the electrophysiological properties was observed with procainamide infusion during AF. In 12 patients, both the local electrogram and monophasic action potentials (MAP) during AF were recorded from the right atrium before, during and after infusion of procainamide (10 mg/kg). The minimum AF cyclelength (CLmin), MAP duration at 90% repolarization (MAPD90) and widths of the intraatrial potentials (WAP) were measured with custom-made computer software. The conduction velocity index (CVI) was determined from the WAP. The wavelength index (WLI = CVI × CLmin) and postrepolarization refractoriness (PRR = CLmin - MAPD90) were calculated. In 6 patients, AF was terminated by procainamide infusion (group A), but not in the other 6 patients (group B). Group A patients showed a biphasic change in the parameters following procainamide infusion. In phase I, the CLmin, MAPD90 and PRR increased, while the CVI decreased, and the WLI remained unchanged. In phase II, the PRR, CVI and WLI increased and the AF was terminated. No restoration of the CVI nor increase in the WLI were observed in group B. The biphasic fluctuation in the CVI and the remarkable increase of the PRR and WLI were observed before termination of AF by procainamide infusion. (Jpn Circ J 1999; 63: 43 - 49)

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Two-dimensional echocardiography has become the procedure of choice to diagnose left ventricular mural thrombi. However, small or flat thrombi may be difficult to distinguish from myocardium. The spatial distribution of the ventricular myocardial blood flow can be imaged with myocardial contrast echocardiography (MCE). The authors presumed that the absence of arterial supply to a fresh thrombus may allow MCE to distinguish between thrombus and myocardium. In the 2 cases presented here, MCE was performed with the same technique as that used for the purpose of visualization of myocardial perfusion; as a result, an apical mural thrombus, indistinct from myocardium before MCE, was visualized as a contrast defect during imaging. Conversely, myocardium that mimicked a thrombus was imaged by MCE as a contrast-opacified area. These findings suggest that MCE after reperfusion therapy is useful to distinguish mural thrombi from myocardium. (Jpn Circ J 1999; 63: 50 - 52)

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The relation between the level of total serum cholesterol and stroke is controversial. The relation between serum total cholesterol and subtypes of stroke was examined in the participants of a community-based mass screening program in Okinawa, Japan. A total of 38,053 subjects, whose serum level of cholesterol had been determined during a mass screening carried out in 1983, were examined to see whether they had experienced stroke during a 3-year period from 1988 to 1991. Of them, 315 subjects aged 33-93 years (174 men, 141 women) had had a stroke during that period. The types of stroke were cerebral infarction in 164, cerebral hemorrhage in 111, subarachnoid hemorrhage in 19, and others in 21. In men, the odds ratio of cerebral hemorrhage was 0.71 (95% confidence interval, 0.55-0.95), and the odds ratio of cerebral hemorrhage associated with serum level of cholesterol ≤167 mg/dl, 168-191 mg/dl, 192-217 mg/dl, and ≥218 mg/dl were 1.00 (reference), 0.70 (0.38-1.30), 0.77 (0.55-1.08), 0.73 (0.56-0.96), respectively. Lower serum cholesterol was an independent predictor of cerebral hemorrhage in men. (Jpn Circ J 1999; 63: 53 - 58)

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A 16-year-old man was found to have an enlarged cardiac silhouette. Primary chylopericardium was diagnosed when pericardiocentesis yielded the characteristic milky-white fluid. The thoracic duct was easily identified by giving milk and butter and an injection of ethylene blue immediately before the operation. Intraoperative thoracic ductography showed no abnormal findings. Mass ligation of the thoracic duct above the diaphragm and partial pericardiectomy were successfully performed through a right thoracotomy approach. In addition, many of the lymphatics were ligated above the diaphragm. The right thoracotomy approach was a useful method for resection and ligation of the thoracic duct just above the diaphragm. Follow-up showed no accumulation of pericardial fluid or pleural effusion. (Jpn Circ J 1999; 63: 59 - 60)

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A 47-year-old woman with severe prolonged anemia developed heart failure. After treatment of the heart failure and anemia, she showed regional dysfunction of the left ventricular wall and myocardial fatty acid metabolism was disturbed in these sites. Coronary arteriography showed normal images. It took about 4 months to recover both left ventricular wall motion and fatty acid metabolism. Prolonged decrease of oxygen supply to the myocardium, which is caused by severe prolonged anemia, seemed to affect the myocardial function in this case, which could be another model of anemia-related myocardial dysfunction. (Jpn Circ J 1999; 63: 61 -63)

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A 68-year-old man suffering from chronic heart failure due to coronary artery disease (CAD) underwent rest technetium-99m (^99mTc)-tetrofosmin and thallium-201 (²⁰¹Tl) with reinjection studies, but died thereafter. The heart was removed and sectioned into short-axis slices and examined by gross and microscopic pathologic methods. A close correlation between the amount of residual cardiomyocytes and the level of regional tracer activity in the left ventricular wall was obtained for redistribution ²⁰¹Tl, reinjection ²⁰¹Tl and rest ^99mTc tetrofosmin images. The correlation coefficients were r=0.901 for the ²⁰¹Tl redistribution images, r=0.913 for the ²⁰¹Tl reinjection images and r=0.917 for the rest ^99mTc-tetrofosmin images. This case report provides further evidence of the validity of SPECT tetrofosmin imaging for the determination of myocardial viability in CAD. (Jpn Circ J 1999; 63: 64 - 67)

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A 54-year-old woman with progressive systemic sclerosis (PSS) was admitted to hospital because of dyspnea and chest pain. Echocardiogram revealed diffuse hypokinesis of the left ventricle (ejection fraction 24%). Methylprednisolone, heparin, and diuretics were administered, without benefit. Anemia, thrombocytopenia, and renal dysfunction rapidly progressed, and she died of heart failure on the 14th hospital day. Immunohistochemical study of the myocardial tissue showed mild to moderate cell infiltration, mainly consisting of natural killer (NK) cells, macrophages, cytotoxic T lymphocytes (CTLs), and T helper cells. Perforin, a cytolytic factor, was expressed in the infiltrating CTLs and NK cells, indicating that these cells were activated killer cells. Furthermore, human leukocyte antigen classes I and II, intercellular adhesion molecule-1, as well as costimulatory molecules B7-1, B7-2, and CD40, all of which are known not to be expressed in cardiac myocytes under normal conditions, were moderately to strongly expressed in cardiac myocytes. There was no detectable level of enterovirus genomes in the polymerase chain reaction products from the myocardial tissue of this patient. These findings strongly suggest that the infiltrating killer cells recognized cardiac myocytes as target cells and directly damaged them by releasing perforin. Enhanced expression of these antigens may have played an important role in the activation and cytotoxicity of the infiltrating killer cells. Absence of enterovirus genomes in the myocardial tissue may suggest that this autoimmune process is primarily induced by PSS. (Jpn Circ J 1999; 63: 68 - 72)

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