Since the original report of Kawasaki disease in 1967¹⁾ more than 150,000 cases have been reported in Japan.²⁾ Although there have been no nationwide epidemics in Japan since 1987, more than 6,000 newly diagnosed cases are reported every year, and the number has been increasing year by year despite the decreasing birth rate. ^2,3) The etiology of the disease is still unknown. High dose intravenous gammaglobulin is currently used during the acute phase in 84 0f the patients in Japan with a concomitant decrease in coronary arterial sequelae.¹⁾ However, 7-13 0f the patients still have persistent coronary artery aneurysms after the acute stage.^2,3) The aneurysms are seen mostly in the proximal coronary arteries, and are often associated with aneurysms in the distal coronary artery segments (Figure 1A, 2A). Most of the patients show a decrease in the size of aneurysms soon after the acute phase (Figure 1B). However, the aneurysms may progress to obstructive lesions even after initial regression (Figures 1C, D, 2B).⁴⁾ Such obstructive lesions may cause sudden death or myocardial infarction. Long term follow-up of coronary artery lesions has revealed several characteristic features, including progressive localized stenosis (Figure 1D), extensive recanalizations (Figure 2D) and development of collateral arteries. ^4-6) Progressive increases in aneurysm size and the appearance of new aneurysms in the late phase have also been reported. The basic mechanisms of the coronary arterial remodeling in Kawasaki disease have not yet been elucidated. Only recently has immunohistochemical staining in formalin-fixed specimens become feasible.⁷⁾ This is a major technical breakthrough since it is almost impossible to obtain fresh frozen specimens of coronary artery lesions of Kawasaki disease.⁸⁾ In this paper, we compare immunohistochemical findings in coronary artery lesions with the corresponding coronary angiographic findings, and attempt to make inferences as to the mechanism of remodeling both in early and late phases of the disease based on the expression of vascular growth factors.⁸⁾

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The objective of the present study was to investigate the differences between coronary hyperresponsiveness without ischemia and vasospastic angina in an ergonovine provocation test using multivariate analysis. We have sometimes experienced a more than 50 arrowing response of vascular diameter without ischemia in a coronary response to ergonovine. We studied 107 patients with less than 50 tenosis in a coronary arteriogram. Their vascular responses to ergonovine were measured and the patients were divided into three groups, as follows: Group 1 had 50 0r less vascular narrowing response without ischemia; Group 2 had a vascular hyperresponsiveness of more than 50 arrowing response without ischemia; and Group 3 experienced a hyperresponsiveness with ischemia. The degree of coronary response was found to be related to smoking, inpaired glucose tolerance (IGT) and the Gensini score by multiple regression analysis. A multiple logistic analysis revealed that the Gensini score and smoking were significant predictive factors for Group 3 (odds ratio: 1.20 and 8.97). The only factor different between Group 2 and Group 1 was gender. The coronary hyperresponsiveness to ergonovine without ischemia differs from vasospastic angina in the degree of coronary atherosclerosis and smoking habits. The patients with hyperresponsiveness had similar characteristics to those with atypical chest pain rather than vasospastic angina, except for a gender difference.

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To evaluate the effects of left ventricular (LV) dysfunction upon the sympathetic nervous and renin-aldosterone-angiotensin systems, neurohormonal factors were measured in patients with ischemic heart disease. Eleven patients were divided into two groups by their LV ejection fraction based on previous catheterization; preserved (EF ≥ 60 %) and impaired (EF < 60 %) LV systolic function groups. They performed supine ergometer exercise and blood samples were drawn at rest and at peak exercise. After dynamic exercise, plasma norepinephrine was significantly (p < 0.05) increased in patients with preserved LV function, whereas it was not altered in patients with impaired LV function (norepinephrine 20.8 ± 20.5 vs 45.8 ± 41.9, respectively). We observed no differences in basal or peak levels of neurohormonal factors, including plasma renin activity, aldosterone, and brain natriuretic peptide (BNP), between the groups. Although the plasma levels of angiotensin I and II were not different in the two groups at rest or at peak exercise, their increasing ratios from rest to peak exercise were significantly higher in patients with impaired LV function compared to those with preserved LV function (angiotensin I ; - 18.6 ± 31.0 % vs 64.8 ± 66.5 %, p < 0.05, angiotensin II; - 5.9 ± 41.2 % vs 60.7 ± 40.4 % , p < 0.05). These results suggest that the increasing ratios of angiotensin I and II are superior to BNP as predictors of LV dysfunction, and that the sympathetic nervous system has already been activated even at rest and did not respond to dynamic exercise in patients with LV dysfunction in ischemic heart disease.

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The capacity of β - blockers to prevent cardiac events in post - myocardial infarction (MI) patients was investigated. Among 1483 study participants, a β - blocker was included in the therapeutic regimens of 833 (β - blocker group) and was omitted from the regimens of 650 (control group). The incidence of cardiac events (recurrent MI, sudden death and death by congestive heart failure) during a follow up period of 17.4 ± 20.9 months was retrospectively compared between the two groups. Cardiac events occurred in 27 (3.2 %) members of the β - blocker group and in 44 (6.8 %) controls, which represents a significant decline in the incidence of cardiac events among patients administered β - blockers (p < 0.01, odds ratio 0.46, 95 % confidence intervals 0.28 - 0.75). Subgroup and multivariate analyses showed β - blockers to be as efficacious in Japanese post - MI patients as was previously shown in Western patients. While these findings are compelling, it is clear that confirmation in a large, multicenter, placebo - controlled, randomized clinical trial, analogous to those that have been carried out in Western countries, is necessary.

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Repolarization abnormalities after radiofrequency ablation in patients with manifest Wolff-Parkinson-White syndrome (WPW) have been attributed to cardiac memory of preexisting changes in repolarization properties. We compared spatial ventricular gradient (VG) from vectorcardiograms with QRST values of 12-lead ECG in 41 patients with WPW (group A, manifest WPW due to left-sided accessory pathway (n = 20); group B, manifest WPW due to right-sided accessory pathway (n = 12); group C, concealed WPW (n = 9)) before and after ablation. Group N (n = 607) served as control. In groups A and B, the abnormalities of spatial VG and QRST values of 12-lead ECG that existed before and 1 day after ablation significantly decreased 1 week after ablation. In group C, spatial VG and QRST values of 12-lead ECG showed no significant changes. The diagnostic ability of spatial VG is almost equivalent to that of the QRST value of ECG in detecting repolarization abnormalities in patients with WPW before and after ablation. We propose a new concept of a "remodeling gradient" directing from the preexcited area to the opposite side of the ventricle as a result of preexcitation-induced electrical remodeling.

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To study the role of antitachycardia burst pacing in patients with reentrant pleomorphic ventricular tachycardia (VT) associated with non-coronary artery diseases, the efficacy of antitachycardia pacing and appropriate antitachycardia pacing cycle length were evaluated in each pleomorphic VT morphology of seven patients. Seven patients were included in this study. Clinically documented pleomorphic VTs were reproduced in an electrophysiologic study. For each VT, rapid ventricular pacing was attempted from the apex of the right ventricle at a cycle length which was 20 ms shorter than that of VT and repeated after a decrement of the cycle length in steps of 10 ms until the VT was terminated or accelerated. All 16 VTs could be entrained by the rapid pacing, and 13 of the 16 VTs (81 %) were terminated, whereas pacing-induced acceleration was observed in the other 3 VTs of the 3 patients. VT cycle length (VTCL), block cycle length (BCL) which was defined as the longest VT interrupting paced cycle length, %BCL / VTCL and entrainment zone which was defined as VTCL minus BCL, varied in each VT morphology of each patient. In two patients, antitachycardia pacing was effective in all VT morphologies and the maximum difference of the %BCL / VTCL among the pleomorphic VTs was less than 10 %. Thus, antitachycardia pacing seemed to be beneficial for these patients. In the other 5 patients, a difference of more than 10 0n %BCL / VTCL was observed among the pleomorphic VT morphologies and / or at least one VT morphology showed pacing-induced acceleration. Compared to the 13 terminated VTs, three accelerated VTs had a wide entrainment zone [160 ± 44 vs 90 ± 48 ms, p < 0.04] and small %BCL / VTCL [61 ± 6 vs 77 ± 11 %, p < 0.03]. In pleomorphic VTs associated with non-coronary artery diseases, responses to rapid pacing was not uniform; VT might be terminable or accelerated even in the same patient. We need to pay close attention when programming antitachycardia pacing in patients with pleomorphic VT.

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The objective of the present study was to evaluate the benefit of β - blocker therapy for patients with Takayasu arteritis complicated by moderate or severe aortic regurgitation. Clinical and echocardiographic evaluation was performed in 20 Japanese women in a follow-up period of 7.0 ± 2.0 years. The patients were divided into 2 groups: Group A (n = 10) patients who did not receive β - blockers, and Group B (n = 10) patients treated with long-term (5.1 ± 1.6 years) therapeutic doses of β - blockers. Left ventricular wall thickness increased significantly in all Takayasu patients who did not receive β - blockers. Consequently, a remarkable increment in left ventricular mass took place (232 ± 59 to 361 ± 79 g; p < 0.005). In the same group, progressive worsening of the symptoms, with no reduction in the percent fractional shortening, was observed in 2 patients, while reduction of this last index was present in 1 asymptomatic patient. On the other hand, among the patients who were treated with β - blockers, left ventricular mass still increased in 6 cases, while it clearly decreased in the other 4 cases (290 ± 171 to 284 ± 61 g; NS). The increment in wall thickness or left ventricular mass observed among patients with β - blocker therapy was clearly less than the one registered among those who had not received β - blockers. Furthermore, no worsening of the symptoms and / or left ventricular performance was observed during the follow-up period for patients receiving β - blockers. We conclude that β - blocker therapy can slow and even reverse the progression of left ventricular hypertrophy in patients with Takayasu arteritis complicated by moderate or severe aortic regurgitation. The mechanism still needs to be elucidated. We believe an effective reduction in the excessive afterload imposed on the left ventricle to be most likely responsible, but cardiac β - receptor up-regulation might also be involved. Deterioration of the clinical status and / or impairment of left ventricular function were not associated with β - blocker therapy in our patients. Therefore, these agents can be used safely alone or in addition to standard anti-hypertensive therapy when attempting to reduce excessive afterload, in spite of the presence of severe aortic regurgitation.

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The mechanisms responsible for regression of left ventricular (LV) mass with antihypertensive therapy in patients with severe hypertension remain unclear. This study was designed to examine whether systolic and diastolic blood pressures are associated with changes in LV mass. Eighteen patients with essential hypertension whose average seated diastolic blood pressure was ≥ 110 mm Hg were enrolled in the study. All patients were administered antihypertensive therapy and underwent M - mode echocardiography before and after 6 months of treatment. In all patients, antihypertensive treatment significantly reduced systolic blood pressure from 175 ± 21 mm Hg at baseline to 143 ± 22 mm Hg at 6 months (p < 0.001), and diastolic blood pressure from 116 ± 7 mm Hg at baseline to 92 ± 20 mm Hg at 6 months (p < 0.001). LV mass index at 6 months was significantly reduced compared to its baseline value (p < 0.05). Change (value at 6 months - value at baseline) in systolic and diastolic blood pressures correlated positively with the change in LV mass index (r = 0.61, p < 0.01 and r = 0.71, p < 0.001, respectively). The patients were divided into responders, whose LV mass regressed by ≥ 10% (n = 9), and nonresponders, whose LV mass regressed by < 10 % (n = 9). Systolic (p < 0.001) and diastolic (p < 0.001) blood pressures, interventricular septal thickness (p < 0.05), posterior wall thickness (p < 0.001), and LV mass index (p < 0.001) were significantly decreased in the responders, but not in the nonresponders, at 6 months compared with those at baseline. Systolic (p < 0.05) and diastolic (p < 0.05) blood pressures in nonresponders were significantly higher than those in the responders at 6 months. The changes in systolic and diastolic blood pressures did not correlate with the change in LV mass index in the responders or the nonresponders. The regression of LV mass is strongly affected by reducing blood pressure. This is the first study using antihypertensive therapy to demonstrate that a change in blood pressure correlates positively with changes in LV mass index in severely hypertensive patients.

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Heart transplantation (HT) provides longer survival than that of the natural history in patients with dilated cardiomyopathy (DCM). However, the optimal timing for cardiac transplantation and predictors of mortality in patients with end-stage cardiomyopathy (ESCM) has been poorly defined. The primary purpose of this study focused on the natural history of ambulatory patients with ESCM for HT assessment. Secondly, we tried to determine prognostic factors of individuals with the poorest short-term outcome and the optimal timing for HT in patients with ESCM. Finally, clinical treatment with angiotensin converting-enzyme inhibitors (ACEIs), carvedilol and amiodarone in the prevention of mortality caused by ESCM, were retrospectively evaluated. The short-term outcomes of 119 referral patients with ESCM for four years were observed. The patients had New York Heart Association class III to IV dyspnea at initial assessment for HT. Left ventricular ejection fraction (LVEF) was 17 ± 6 % and cardiac index (CI) was 2.0 ± 0.6 l / min / m². After optimization of medical treatment, the patients were divided into two major groups according to CI equal to or less than 2.0 l / min / m² and more than 2.0 l / min / m². HTs were accepted in 88 patients and the patients were divided into two groups: medical treatment (group 1, 56 patients) or HT (group 3, 32 patients); HT was not accepted in the other 31 patients (group 2). We studied the probability of the survival curve and prognostic variables of the groups with medical treatment in the follow-up of 12 ± 9 months. During follow-up, 49 patients were alive without HT. The remaining 38 patients died; 27 patients were in group 1 and 11 patients were in group 2. Eight deaths in group 2 were sudden. The actuarial survival rate among the non-HT population was 73 %, 68 %, 63 %, and 56 % at 3, 6, 9 and 12 months, respectively. The actuarial survival rate among group 1 was 70 %, 59 %, 55 %, and 52 % at 3, 6, 9 and 12 months, respectively. The actuarial survival rate among group 2 was 87 %, 85 %, 77 %, and 65 % at 3, 6, 9 and 12 months, respectively. A comparison, excluding patients with HT, was performed with those who had survived < 1 year and ≥ 1 year after assessment, and those who had died. Two parameters were independent predictors of prognosis on univariate and multivariate analysis: total pulmonary vascular resistance (TPR) ≥ 14 Wood units (W) and CI < 1.65 l / min / m² at 6 and 12 months after assessment. Treatment with amiodarone for ventricular tachycardia (VT) showed no convincing role in the prevention of sudden death in our patients. Also, treatment with ACEIs or carvedilol for heart failure was unconvincing to improve the short-term outcome in this study. Our results suggest in properly selected patients that HT should be considered within six months among patients with severe heart failure. Hemodynamic parameters associated with right cardiac function are important determinants of mortality caused by progressive heart failure. Predictors such as CI and TPR may be considered as important markers of mortality in prediction of short-term outcome in patients with ESCM, as other predictors reported in the literature.

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Recently, it has been demonstrated that polymorphonuclear neutrophils (PMNs) affect coronary vascular tone. We have reported that unstimulated PMNs constrict the porcine proximal coronary artery. However, the mechanism (s) of interaction between PMNs and coronary artery and the regional differences in susceptibility of the coronary arterial tree have not been fully explored. We examined changes in the isometric tension of porcine distal coronary arterial rings caused by unstimulated PMNs, in which the levels of superoxide anion detected by the cytochrome C method were slight when unstimulated and significant when stimulated with A23187. Unstimulated PMNs relaxed the distal coronary artery and the effect was suppressed by endothelial denudation, indomethacin and the prostacyclin synthetase inhibitor, tranylcypromine. During vasorelaxation, prostacyclin was produced (n = 8, with / without relaxation; 596 ± 76 / 247 ± 26 pg / ml, p < 0.01) and was considered, therefore, to be the vasodilatory substance responsible for the action. These results suggest that PMNs modulate coronary arterial tone via an interaction between PMNs and endothelium and the release of vasodilating prostaglandins, of which prostacyclin is considered to be one of the substances responsible. Further, the effect differed markedly depending on the site of the coronary artery. In vivo, coronary artery tone is complexly regulated, therefore, the relative contribution of the present PMN-endothelial cell interaction observed in vitro is unclear.

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We explored the mechanism through which patients sometimes show immunosuppression after cardiac surgery. To test the hypothesis that commonly used drugs could cause apoptosis of immune cells, the proapoptotic effects of heparin and catecholamines (dopamine and dobutamine) on peripheral blood lymphocytes were evaluated. Peripheral blood lymphocytes were purified from blood samples of normal healthy volunteers. These cells were cultured in the presence of heparin, dobutamine or dopamine. The apoptosis was quantified by Annexin V fluorescent assay, by DNA content and by morphological assessment. Lymphocytes did not show significant levels of apoptosis induction after 24 hours of incubation with heparin. Both dopamine and dobutamine demonstrated a clear apoptosis inducing effect on lymphocytic population after 24 and 48 hours of culture, in concentrations comparable with the clinically used levels. Apoptosis was time and concentration dependent for both catecholamines. The dopamine and dobutamine effect on lymphocyte viability was due, at least partially, to lymphocyte β receptor engagement, as proved by blocking the receptor with propranolol. These results suggest that catecholamines could induce apoptosis of lymphocytes. This finding may be associated with immunosuppression observed in patients undergoing cardiac surgery.

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Familial long QT syndrome (LQTS) is caused by mutations in genes encoding ion channels important in determining ventricular repolarization. Mutations in at least five genes have been associated with the LQTS. Fire genes, KCNQ1, HERG, SCN5A, KCNE1, and KCNE2, have been identified. We have identified a missense mutation in the HERG gene in identical twins in a Japanese family with LQTS. The identical twins in our study had QT prolongation and the same missense mutation. However only the proband had a history of syncope. Although many mutations in LQT genes have been reported, there are few reports of twins with LQTS. This is the first report, to our knowledge, of identical twins with a HERG gene mutation.

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A 74-year-old man received oral administration of pilsicainide, a pure sodium channel blocker with slow recovery kinetics, to convert paroxysmal atrial fibrillation to sinus rhythm and developed loss of consciousness two days later. The ECG monitoring revealed sinus pause with markedly prolonged PQ interval and QRS width. Two days after the drug was discontinued, the duration of the QRS complex was normalized. This drug is rapidly absorbed from the gastrointestinal tract, most of which is excreted from the kidney. The plasma concentration of pilsicainide, although not measured, must have been very high, since his renal function was impaired. When pilsicainide is prescribed in patients with coronary artery disease or renal dysfunction, close attention must be paid to avoid life-threatening arrhythmias due to high plasma concentrations of the drug. This is an interesting case because the proarrhthmia of the drug was not tachyarrhythmia, such as ventricular tachycardia or torsades de pointes, but sinus pause.

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We encountered a case of mitral stenosis, complicated with non-bacterial thrombotic endocarditis, that developed after percutaneous transvenous mitral commissurotomy (PTMC). A 71-year-old female Japanese patient had severe congestive heart failure and underwent PTMC for critical and severely calcified mitral stenosis. Four weeks later, the echocardiogram demonstrated a highly echoic protrusion in the postero-medial commissure of the mitral valve. There was little evidence of inflammation at that time. She had been anticoagulated adequately since she was admitted. The patient underwent replacement of the mitral valve. She did not show any evidence of systemic embolization. Microscopic evaluation showed only organized thrombus but no evidence of inflammation in the mitral valve. Silent development of non-bacterial thrombotic endocarditis after PTMC should be recognized as a rare but potentially lethal complication of PTMC.

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