Hyperinsulinemia is related to coronary artery disease (CAD), as an indication of decreased insulin sensitivity. Although there are many studies showing the relation between fasting insulin levels and insulin resistance, there are fewer studies on postprandial insulin levels. The aim of the present study was to investigate the relationship between postprandial insulin levels and CAD and its extent in our patients. For this purpose, oral glucose tolerance testing was performed in 222 patients with no known diabetes and who were scheduled to undergo diagnostic coronary angiography. The patients were first separated into two groups, one group (group I) having an insulin response within reference values to oral glucose loading, and the other group (group II) with a higher than normal insulin response. The presence and extent of CAD in the two groups were compared. While 65% of the patients in group 1 had CAD, this rate increased to 79% in group 2 patients (P = 0.02). The mean vessel scores were 0.92 ± 0.78 in group 1 and 1.67 ± 0.99 (P < 0.0001) in group 2 patients. The stenosis scores were 2.192 ± 2.077 in group 1 and 5.588 ± 3.519 (P < 0.001) in group 2, while the extent scores were 1.230 ± 1.292 in group 1 and 2.729 ± 1.847 in group 2 (P < 0.0001). The differences between the two groups were significant. Postprandial insulin values were positively correlated with CAD (P = 0.001, r = 0.214), vessel scores (P < 0.0001, r = 0.326), stenosis scores (P < 0.0001, r = 0.261), and extent scores (P < 0.0001, r = 0.419). Logistic regression analysis revealed hyperinsulinemia increased CAD independent from the other risk factors (OR = 5.742, CI 95%: 1.809-18.227, P = 0.003).

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The aim of the present study was to investigate the prognostic significance of time-delay to peak creatine kinase (CK) after successful direct percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI).
Our 240 consecutive first AMI attack subjects admitted within 5 hours from onset were successfully reperfused by direct PCI therapy. Subjects were divided into two groups according to the upper quartile value of peak-CK time from onset, the early peak-CK group (peak-CK time ≤ 16 hours from onset, n = 180) and the late peak-CK group (peak-CK time > 16 hours, n = 60).
(I) The early ST-segment resolution rate was lower in the late peak-CK group compared with the early peak-CK group (P < 0.05), and there were significantly fewer patients with preinfarction angina pectoris in the late peak-CK group than in the early peak-CK group (P < 0.01). (II) LVEF in the chronic stage was significantly lower in the late peak-CK group than in the early peak-CK group (49 ± 13% versus 57 ± 13%, P < 0.001). (III) There were significantly more patients with major complications in the late peak-CK group than in the early peak-CK group (required CABG: 10% versus 3%, P < 0.05; cardiac death: 18% versus 3%, P = 0.0001). (IV) Multivariate analysis identified late peak-CK as an independent predictor of cardiac death (Odds ratio 7.91, 95% C.I. 1.40-44.11, P < 0.05).
In patients with AMI, the time-delay to peak-CK after successful direct PCI may be closely related to left-ventricular systolic dysfunction and poor patient outcome, including mortality.

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The appropriate surgical strategy for patients with combined carotid and coronary artery disease remains controversial. We retrospectively compared our surgical results for 2 types of approaches in this disorder.
The records of 76 patients consecutively operated on for carotid and coronary artery disease between August 1993 and October 2004 were reviewed. There were 18 males (66.6%) and 9 females (33.3%) in group I. Group II consisted of 35 males (71.4%) and 14 females (28.5%). The patients were divided into two groups: patients with combined off-pump coronary artery bypass and carotid endarterectomy (group I, n = 27), and those with one-stage on-pump coronary artery bypass and carotid endarterectomy (group II, n = 49). Surgical mortality and morbidity and late outcome were compared among the two groups.
The average number of grafts was 1.2 ± 0.4, with the average operative time of 3.3 ± 0.3 hours in group I, and 2.3 ± 0.5 grafts with operative time of 4.6 ± 0.4 hours in group II (P < 0.001 and P < 0.001, respectively). There was 1 death (3.7%) in group I and 2 deaths (4.8%) in group II (P = 0.937). No patient from either group I or group II had postoperative stroke. Mean hospital stay was 7.4 ± 1.9 days in group I and 11.3 ± 1.7 days in group II (P < 0.001). At a mean follow-up of 5.5 ± 3.3 years in group I, 1 patient had contralateral carotid endarterectomy (3.7%). Group II had a mean follow-up of 5.2 ± 3.0 years and contralateral carotid endarterectomy was performed in 1 patient (2.0%). There were no late strokes or deaths in either group.
Combined coronary artery bypass grafting and carotid endarterectomy using 2 different types of technique is a safe and effective procedure in patients with significant concomitant monolateral carotid and coronary artery disease.

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Impaired oxygenation sometimes occurs in patients with acute aortic dissection, however, the mechanism has not been fully investigated. We hypothesized that impaired oxygenation is related to inflammation secondary due to aortic dissection. Patients with acute aortic dissection who had received 14 days of conservative treatment were retrospectively examined. Patients who had undergone surgery or died within 14 days were excluded. Patients who had evidence of having pneumonia or pulmonary congestion during this period were also excluded. Twenty-six patients were divided into a preserved oxygenation group (minimum oxygenation index ≥ 200, n = 13) and an impaired oxygenation group (minimum oxygenation index < 200, n = 13). Maximum serum C-reactive protein (max CRP) and other factors (age, gender, hypertension, diabetes mellitus, smoking, hyperlipidemia, Stanford type, thrombosed false lumen, pleural effusion, atelectasis, use of intravenous vasodilators) for the two groups were compared. Max CRP was the only predictor for impaired oxygenation as calculated by single/multiple logistic regression analysis. Max CRP was significantly higher in the impaired oxygenation group (20.1 ± 2.1 mg/dL) than in the preserved oxygenation group (10.5 ± 1.4 mg/dL, P < 0.05). These results suggest that impaired oxygenation is related to inflammation, which is secondary due to acute aortic dissection.

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Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular morbidity and mortality. Inflammatory processes associated with OSAS may contribute to cardiovascular morbidity in these patients. C-reactive protein (CRP) is an important serum marker of inflammation. We tested the hypothesis that patients with OSAS have increased plasma CRP.
After 173 male subjects underwent polysomnography, 94 were considered to have OSAS (apnea-hypopnea index (AHI) > 5), 38 cardiovascular disease (CVD), and 56 without CVD. Seventy-nine subjects were considered not to have OSAS (AHI < 5) and from among these 57 patients without CVD were enrolled as control subjects.
Serum CRP levels were significantly elevated in the OSAS + CVD group compared to the two other groups (P < 0.05). When we evaluated the association between the serum CRP level and severity of OSAS, CRP levels were positively correlated with AHI in OSAS patients (r = 0.61, P < 0.001)
OSAS, as a marker of inflammation and cardiovascular risk, is associated with elevated levels of CRP. According to these results, the link between cardiovascular morbidity and OSAS may be explained by the coexistence of other cardiovascular risk factors such as circulating CRP levels.

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A prospective cross sectional analysis of serum lipids was carried out in 20 children aged between 1.3 and 16 years with Kawasaki disease (KD). The controls were siblings of other patients. The mean interval between diagnosis of the disease and time of assay was 2.6 years (range 0.41 to 6 years). Standard biochemical methods were employed for determination of various components of the lipid profiles. There were significant differences in high-density lipoprotein cholesterol (HDL-C) (40.37 ± 12.0 mg/dL versus 53.49 ± 4.31 mg/dL, P < 0.001) and low-density lipoprotein cholesterol (LDL-C) concentrations (77.76 ± 26.25 mg/dL versus 57.7 ± 23.2 mg/dL, P < 0.05) between the cases and controls. Lower HDL-C levels persisted at 1-3 and more than 3 years of disease duration. No significant differences were seen in the values of other parameters in the lipidogram, such as total cholesterol (TC), triglycerides (TG), and very low-density lipoprotein cholesterol (VLDL-C). Premature atherosclerosis that occurs in KD may be secondary to these lipid metabolism abnormalities.

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The purpose of this prospective, quantitative, comparative study, conducted at the 55 bed cardiothoracic intensive care unit of the Heart Institute (InCor), University of Sao Paulo Medical School, was to identify factors involved in the weaning of patients who require long-term (> 10 days) mechanical ventilation after cardiac surgery.
The subjects included all patients who underwent open-heart surgery with cardiopulmonary bypass during a 10 month period from April 2000 to January 2001 (n = 946). From this group, 52 (5.7%) patients who required a tracheotomy for the management of long-term mechanical ventilation after cardiac surgery with cardiopulmonary bypass were selected. Pre-, intra- and postoperative data from patients who were not successfully weaned after reintubation and who underwent an elective tracheotomy were compared.
Parameters of respiratory mechanics such as respiratory complications, oxygenation, and cardiac, renal, and neurological function were evaluated. Weaning success was defined as the ability of a patient to tolerate 48 hours without pressure or flow support from a mechanical ventilator. A patient was considered to have failed weaning if they died or remained under ventilation for more than 8 weeks. Of the 52 patients studied, 25 were successfully weaned, 21 died, and 6 remained ventilated for more than 8 weeks. We found significant statistical differences (P < 0.05) between the groups with respect to success or failure in LVEF (P = 0.0035), the need for vasoactive agents (P = 0.0018), and renal failure (P = 0.002). Parameters of respiratory mechanics and oxygenation (eg, static airway compliance, airway resistance) did not influence the success or failure of weaning. There was a significant difference in relation to the presence of pneumonia (P = 0.0086) between the two groups. Although neurological complications were more frequent in patients in the weaning success group, the failure group had lower GCS scores, which is indicative of worse prognoses.
It is concluded that cardiac dysfunction, the need for dialysis, and pneumonia are determinants for weaning failure in patients undergoing long-term mechanical ventilation after cardiac surgery.

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To prevent coronary artery disease, it is necessary for patients with familial hyper-cholesterolemia (FH) to maintain a low cholesterol level. Recently a combination therapy of low-density lipoprotein (LDL) apheresis and statins has been used for FH patients, but their long-term prognosis over 10 years is unknown.
In this single center prospective report, 18 FH patients with severe coronary stenosis received LDL apheresis every 2 or 4 weeks and statin therapy for 9.8 ± 3.0 years. Probucol was given to 17 of the 18 patients. We observed their clinical events as well as coronary stenosis findings and ejection fractions for 10.7 ± 2.6 years.
Total and LDL cholesterol levels before therapy were 345 ± 46 and 277 ± 48 mg/dL, respectively. Immediately following LDL-apheresis, these levels decreased to 104 ± 7.5 and 66 ± 16 mg/dL, respectively. There were no cardiac deaths and 4 patients were free from any coronary events. There was one noncardiac death. Nonfatal myocardial in-farction occurred in 2 patients and coronary bypass surgery was required in one patient. Twelve patients received additional coronary angioplasty. There was little change in coronary stenosis and ejection fraction following 10 years of the combination therapy. Univariate Cox regression analysis revealed that the calculated mean LDL cholesterol level was the predictive value of treatment efficacy (mean LDL cholesterol < 140 mg/dL, hazard ratio 0.23, P = 0.028). The combination therapy of LDL-apheresis and antilipid drugs delayed the progression of coronary atherosclerosis and prevented a major cardiac event, although complete inhibition was limited to a small group. Additional coronary angioplasty is likely to be required for a favorable clinical outcome in FH patients.

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Heart rate recovery is the difference in heart rate at peak exercise and at a specific time interval following the onset of recovery. Attenuated heart rate recovery is an independent predictor of mortality in patients with a history of coronary artery disease. The aim of the present study was to evaluate the effect of a statin on heart rate recovery, particularly in patients with ischemic heart failure and hyperlipidemia. Twenty-nine consecutive hyperlipidemic, stable coronary artery disease patients with heart failure and 19 healthy subjects were enrolled. Heart rate recovery values at the 1st and 3rd minutes and lipid profiles of the patients were evaluated at baseline and following 3 months of treatment with fluvastatin. Compared with healthy subjects, the heart rate recovery values were significantly lower in the heart failure patients in both the 1st and 3rd minutes, respectively (31 ± 6 versus 19 ± 7, P < 0.0001; 66 ± 7 versus 47 ± 8, P < 0.0001). Heart rate recovery in the 1st and 3rd minutes increased from 19 ± 7 to 24 ± 9 and 47 ± 8 to 57 ± 11, respectively, following treatment (P < 0.001, P < 0.001). There were no significant correlations among the changes in lipid parameters or HRR in the first and third minutes in the recovery period. The results revealed an improvement in heart rate recovery in heart failure patients by fluvastatin treatment. If this association can be confirmed by other studies, it would be interesting to perform further studies into the mechanism underlying this finding.

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In 2003, a lump-sum payment system based on Diagnosis Procedure Combinations (DPC) was introduced to 82 specific function hospitals in Japan. While the US DRG/PPS system is a “per case payment” system, the DPC based payment system adopts a “per day payment.” It is generally believed that the Japanese system provides as much of an incentive as the DRG/PPS system to shorten the average length of stay (LOS). We performed an empirical analysis of the effect of LOS shortening on hospital revenue and expenditure under the DPC-based payment system, particularly in cardiovascular diseases. We also point out fundamentally controversial aspects of the current system.
A total 109 cases were selected from patients hospitalized at the University of Tokyo Hospital from May to July, 2003 and classified into one of three categories: (1) cardiac catheter interventions, (2) cardiac catheter examinations, and (3) other conservative treatments. We analyzed the changes in profit per day in cases of a reduction in average LOS and an increase in the number of cases.
In category (1) profit increased significantly in conjunction with reduced LOS. In category (2) profit increased only minimally. In category (3), profit increased rarely and sometimes decreased.
In cases of conservative treatment, profits sometimes decreased because an increase in material costs exceeded the increase in revenue. It therefore became clear that the DPC-based payment system does not decisively provide an economic incentive to reduce LOS in cardiovascular medicine.

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Calcitonin gene-related peptide has potent vasodilatory and inotropic actions. The aim of this study was to characterize the changes in this peptide in children with varying degrees of heart failure secondary to congenital heart disease with left to right shunt and to assess its relationship to systolic pulmonary arterial pressure.
Plasma calcitonin gene-related peptide levels were measured in 131 children including 13 healthy ones, 43 with various degrees of heart failure secondary to congenital heart disease, and 75 with congenital heart disease without heart failure.
In patients with heart failure, calcitonin gene-related peptide concentrations were markedly elevated (15.8 ± 2.1 pg/mL) as compared with healthy control subjects (7.0 ± 0.8 pg/mL, P < 0.05) or patients with congenital heart disease but without heart failure (18.6 ± 1.2 pg/mL, P < 0.01). Compared with the controls, there were highly significant stepwise increases in the calcitonin gene-related peptide levels in the mild (n = 15), moderate (n = 12), and severe (n = 16) heart failure subgroups by 1.5, 1.7 and 3.4 fold, respectively. The plasma calcitonin gene-related peptide levels also correlated directly with the pulmonary arterial systolic pressure (r = 0.515, P < 0.0001).
The results of this study indicate that congestive heart failure secondary to congenital heart disease with increased pulmonary flow is associated with elevated levels of calcitonin gene-related peptide that are related to disease severity. Pulmonary overcirculation may play a role in upregulation of calcitonin gene-related peptide in congestive heart failure.

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Bradykinin (BK) is one of the triggers of ischemic preconditioning. Protein kinase C (PKC) and mitochondrial ATP-dependent potassium (K_ATP) channels are central factors in cardioprotection afforded by BK. However, the role of nitric oxide (NO) in the early phase protection of preconditioning with BK is not well understood. We assessed the signaling pathway of the early phase protection of pharmacological preconditioning afforded by BK. Isolated perfused rat hearts (n = 8/group) were subjected to 30-minute global ischemia and 50-minute reperfusion. Left ventricular systolic pressure (LVSP) was recorded prior to the global ischemia and at the end of reperfusion. Preconditioning with BK was induced by two cycles of 5-minute infusion of BK (0.5 μmol/L) and 5-minute washout prior to the global ischemia. To examine participants in the signaling pathway, 5-hydroxydecanoate (5-HD, 200 μmol/L), chelerythrine (CH, 5 μmol/L), or N^ω-nitro-L-arginine methyl ester (L-NAME, 50 mmol/L) was added to the perfusate for 5 minutes prior to the infusion of BK. Pharmacological preconditioning by BK improved postischemic recovery of LVSP (+ 45.1% versus control, P < 0.01). Protection by BK was abolished by coadministration of CH, 5-HD, or L-NAME.
BK affords myocardial protection in the early phase of pharmacological preconditioning through a pathway that includes endogenous NO, PKC, and mitochondrial K_ATP channels.

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Patients with diabetes mellitus (DM) have advanced atherosclerosis compared with nondiabetics. Restenosis after intracoronary stent implantation occurs frequently in diabetic patients. Angiotensin II is an important growth factor for the development of neointimal hyperplasia after vascular injury. The aim of our study was to evaluate the relationships between angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and coronary artery disease (CAD) and stent restonosis in diabetic patients.
One hundred and thirty consecutive patients with CAD and 47 consecutive patients (14 males, mean age, 58.0 ± 10.0) without CAD were enrolled in the study. All patients had type 2 (noninsulin dependent) DM. The patients with CAD underwent percutaneous transluminal coronary angioplasty (PTCA) and stenting. Ninety-four (59 males, mean age, 60.3 ± 9.8) underwent control coronary angiography at the end of the follow-up period (mean duration, 9.1 ± 2.9 months). ACE gene I/D genotyping was identified in all patients.
No significant difference was found among patients with and without CAD with respect to ACE gene I/D polymorphism (P = 0.460). In the control coronary angiography, stent restenosis and new lesion development were comparable in each genotyping subgroup. However, a significant relationship was observed between restenosis and the use of ACE inhibitors (ACEI) in patients with D allele (ACEI ratio, 43.5% in the restenosis group and 56.5% in non-restenotic group, P < 0.05).
We did not find any relationship between ACE gene I/D polymorphism and CAD and stent restenosis and new lesion development in diabetic patients. On the other hand, ACEI treatment may reduce stent restenosis in type 2 diabetic patients with D allele (DD or ID).

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We report a case of atrioventricular nodal reentrant tachycardia coexistent with atresia of the coronary sinus ostium. Radiofrequency current application between the supposed coronary sinus ostium and the tricuspid valve was effective at eliminating the tachycardia. A coronary venogram obtained by left coronary arteriography was useful for guiding the mapping catheter to the successful ablation site.

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A patient with an implantable cardioverter-defibrillator (ICD) experienced inappropriate shocks. X-rays revealed that the ventricular lead was fractured at a point, which seemed to be in a mechanical stress-free space in the heart. Multiple leads were entwined making a short flexible section sandwiched between the entwined area and the stiff coil susceptible to the stress from heart beats. The present case shows that indirect concentrated stress caused by restriction of lead flexibility can result in lead fracture. Upon implanting multiple endocardial leads, attention should be given to the relative position of each lead.

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We describe here the case of a 58-year-old female patient who experienced inappropriate shocks from her implantable cardioverter-defibrillator (ICD). Stored electrograms from her ICD showed high frequency noise preceding the shock. Although the pacing threshold was normal and lead fracture was not found in chest X-rays, pacing lead impedance decreased to 480Ω. Moreover, such high frequency noise was observed by electrogram telemetry, but not by routine evaluation every 3 months. ICD lead dysfunction was suspected, so we elected to replace the ICD lead system. At the time of the operation, lead impedance was 410Ω and pacing threshold was the same as it was at the time of the ICD implantation, and no lead insulation disturbances were observed in the generator pocket. However, manipulation of the lead system produced high frequency noise reproducibly. Since some of the ICD lead dysfunction initially was clinically silent at rest, dysfunction was difficult to detect before serious problems occurred. Therefore, more careful evaluation of the ICD lead system is needed during long-term follow-up of ICD implants.

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Syncope can be caused by either cardiogenic or noncardiogenic causes. Structural heart diseases should be considered as a possible cause of recurrent episodes of syncope if no other causes are found. We report an 18 month-old girl who presented with recurrent syncope as well as dyspnea, failure to thrive, and frequent episodes of pulmonary infections, suggesting congestive heart failure. A prominent pulmonic component of the second heart sound and congested lungs noted from chest X-rays indicated pulmonary hypertension. An echocardiogram revealed an abnormal membrane with a small orifice in the left atrium (LA). An intact atrial septum and no evidence of other congenital heart diseases were observed. The result after surgical resection of the membrane was good during follow-up. Cor triatriatum may be one of the structural heart diseases responsible for repeated unexplained syncope. An echocardiogram performed by an experienced cardiologist would facilitate the diagnosis considerably and an excellent prognosis can be achieved via surgical resection of the obstructing membrane.

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A 72-year-old man was referred for further assessment of a chronic cough. He noticed an association between the episodes of coughing and palpitations. Electrocardiography (ECG) revealed normal sinus rhythm and sporadic unifocal ventricular premature contractions (VPCs). Each cough was preceded by a premature beat. Continuous wave Doppler echocardiography revealed a VPC-induced transient increase in the pulmonary artery blood flow. He was successfully treated for VPCs with oral disopyramide, resulting in subsidence of both the coughing and palpitations. We suspect that the VPC-induced hemodynamic changes in the pulmonary circulation might be responsible for coughing in our patient. Premature contractions should be considered as a possible cause of chronic dry cough in the clinical setting.

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A 69-year-old female suffering from third-degree atrioventricular block with syncope underwent permanent pacemaker implantation. However, she developed shortness of breath 2 months after the implantation. Blood tests revealed elevated levels of LDH, CRP, BNP, and SIL-2R. Transthoracic echocardiography showed thickened left and right atrial walls with mild pericardial effusion. A diagnosis was made based on a CT scan and histology. Although most primary cardiac malignant lymphomas are associated with a poor prognosis, the patient was treated successfully with chemotherapy.

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A 62-year-old woman was struck by lightning while on a mountain and fortunately did not suffer burns or unconsciousness. She stayed at a mountain lodge overnight and was taken to our hospital by helicopter the next day. Upon admission, electrocardiography showed ST segment elevation indicating acute lateral myocardial infarction, and echocardiography showed takotsubo-shaped hypokinesis of the left ventricle indicating an apical aneurysm. Her serum escaped enzyme levels were increased, as is typical in cases of myocardial infarction, however, she did not complain of cardiac symptoms. Coronary arteriography performed 4 days after admission showed a normal coronary artery while left ventriculography showed apical akinesia. An echocardiogram obtained 2 days later showed resolution of the LV wall motion abnormality. This is the first reported case of takotsubo cardiomyopathy caused by lightning. Takotsubo-shaped hypokinesis is not described as a complication of lightning-induced cardiac injury and its pathogenesis remains controversial.

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