This study tested the hypothesis that activated toll-like receptor-4 (TLR-4) is closely related to combined major adverse clinical outcomes (MACO) [defined as advanced Killip score (≥ 3), overt congestive heart failure (CHF) (New York Heart Association functional class ≥ 2) or 30-day death] in patients with ST-segment elevation (ST-se) acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). We conducted a prospective cohort study in 43 consecutive patients with ST-se AMI of onset < 12 hours who were undergoing primary PCI. Blood samples for TLR-4 and serum level of tumor necrosis factor-α (TNF-α) were collected from 43 patients at 24 hours after AMI and from 20 normal outpatients. The experimental results revealed significantly higher baseline levels of TLR-4, TNF-α and white blood cell (WBC) count in the study patients than in normal control subjects (all P < 0.0001). Additionally, baseline levels of TLR-4, TNF-α , creatinine, peak level of CK-MB, and multiple vessel disease were significantly higher, whereas left ventricular performance was notably lower in patients (n = 18) with occurrence of MACO than in patients (n = 25) without occurrence of MACO (all P < 0.05). Furthermore, the level of lipopolysaccharide (LPS)-stimulated LTR-4 was significantly increased in MACO patients than in those without MACO (P < 0.0001). Moreover, LPS-stimulated TLR-4 was the most independent predictor of 30-day MACO (P < 0.01). In patients with ST-se AMI, activated TLR-4 is independently predictive of 30-day MACO.

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Despite increased risk for coronary artery disease and acute myocardial infarction (AMI), prior studies have found that smokers with AMI have lower mortality rates than nonsmokers, a phenomenon often termed ‘smoker’s paradox’. The present study was designed to examine the etiology of ‘smoker’s paradox’, especially with respect to the association with inflammation.
The subjects included 528 consecutive AMI patients who were admitted within 24 hours of onset and underwent successful coronary intervention. Of the 528 subjects, 232 (44%) were smokers.
The cardiac mortality rates over a 6 month period was significantly lower in the smoking group than the nonsmoking group (3% versus 9%, P = 0.01). There were significantly more male patients in the smoking group, and the smoking group was significantly younger than the nonsmoking group (P < 0.0001). The value of high sensitivity C-reactive protein (hs-CRP) on admission and 24 hours after onset, and serum amyloid A protein (SAA) were significantly higher, and acute phase BNP was significantly lower (hs-CRP on admission 1.36 ± 1.03 mg/dL versus 0.75 ± 0.82 mg/dL, P = 0.02, hs-CRP at 24 hours 3.86 ± 4.32 mg/dL versus 2.90 ± 3.46 mg/dL, P = 0.008, SAA; 288 ± 392 μg/dL versus 176 ± 206 μg/dL, P < 0.05, BNP; 248 ± 342 pg/mL versus 444 ± 496 pg/mL, P = 0.0002) in the smoking group than in the nonsmoking group. The early ST-segment resolution rate was higher in the smoking group compared with the nonsmoking group (80% versus 66%, P = 0.003).
The reason why smokers with AMI have lower mortality rates than nonsmokers, the so-called ‘smoker’s paradox’, is believed to be because smoking induces inflammation and smokers may have less damage to microvascular function after primary percutaneous coronary intervention.

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Although in many cardiac surgery centers pharmacological strategies based on fibrinolytic inhibitors are used on a routine basis, detailed knowledge of fibrinolysis during various settings of coronary surgery is still limited.
Sixty-five patients scheduled for coronary surgery were randomized into 3 groups: group A - conventional coronary artery bypass grafting, group B - off-pump surgery, and group C - coronary artery bypass grafting with modified, rheoparin coated cardiopulmonary bypass with the avoidance of reinfusion of cardiotomy blood into the circuit. The sampling time points for rotation thromboelastographic evaluations were as follows: preoperatively, 15 minutes after sternotomy, on the completion of peripheral bypass anastomoses, at the end of the procedures, and 24 hours after the end of surgery. D-dimer levels were evaluated before surgery, at the end of procedures, and 24 hours after surgery.
Thromboelastographic signs of fibrinolysis (evaluated by Lysis Onset Time-intergroup differences at 60 and 150 minutes of assessment: P = 0.003 and P < 0.001, respectively) were clearly detectable during cardiopulmonary bypass in group A, but not at any time in groups B and C. At the other sampling times all thromboelastographic parameters were similar in all groups. In group A, no exceptional bleeding tendency (during 24 hours), as compared to groups B and C (geometric means and 95% confidence intervals: group A: 686.7 [570.8; 826.1] mL, group B: 555.3 [441.3; 698.9] mL, group C: 775.6 [645.1; 932.3] mL, P = 0.157), and no significant correlations between Lysis Onset Time, postoperative blood loss, and D-dimer levels were found. No significant differences in postoperative blood loss related to cardiac surgeons and assistant surgeons were detected.
Thromboelastographic signs of increased fibrinolysis were detectable in the important proportion of coronary surgery patients operated on with the use of conventional cardio-pulmonary bypass, but not in off-pump patients and those operated on with the biocompatible surface-modified circuit without reinfusion of cardiotomy suction blood. These signs resolved spontaneously at the end of surgery and were not associated with increased postoperative bleeding. No significant correlation with D-dimer levels was found.

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Tachycardia-induced cardiomyopathy is characterized by ventricular systolic dysfunction and congestive heart failure resulting from persistent or highly frequent tachyarrhythmias with uncontrolled heart rate. While reversible and often considered benign, few studies have examined the outcome of the disorder.
The clinical characteristics, treatment, and long-term outcomes of 12 consecutive patients with tachycardia-induced cardiomyopathy (9 men, age, 51.9 ± 17.6 years) were studied. The mean period between the occurrence of tachyarrhythmias and the development of congestive heart failure was 26.0 ± 34.3 days. The mean heart rate on admission was 156.3 ± 28.7 beats/min. All patients had severe heart failure with a NYHA functional class of 2.3 ± 0.5, left ventricular ejection fraction of 0.32 ± 0.10, and brain natriuretic peptide level of 505.7 ± 449.1 pg/mL. In all patients, cardiac dysfunction recovered after 53.5 ± 61.3 days. During the follow-up of 53 ± 24 months, 2 patients had a recurrence of heart failure with uncontrolled tachyarrhythmia and 1 patient died suddenly.
In tachycardia-induced cardiomyopathy, recurrent heart failure with uncontrollable tachyarrhythmia and sudden death were observed after recovery from cardiac dysfunction. A substrate for heart failure and/or life-threatening arrhythmia might persist, and careful, long-term follow-up seems required.

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HMG-CoA reductase inhibitors (statins) have recently been reported to improve cardiac function, and decrease the incidence of heart failure (HF) in hyperlipidemic patients. However, evidence for statin treatment in patients with HF remains a subject of debate. Thus, a study was initiated to examine the effects of pitavastatin on cardiac function evaluated by echocardiographic findings and plasma brain natriuretic peptide (BNP) levels in patients with HF. Twenty-three patients with HF were treated with pitavastatin 1-2 mg/day in addition to standard therapy for 7.5 ± 3.8 months. Left ventricular end-diastolic dimension (LVDd) and left ventricular end-systolic dimension (LVDs) were determined by echocardiography. Left ventricular ejection fraction (LVEF) was calculated using Teichholz's formula. Serum lipid and plasma BNP levels were also measured. During the follow-up period, LVEF was increased from 42 ± 11 to 48 ± 13% (P = 0.002). LVDs was reduced from 43 ± 10 to 40 ± 10 mm (P < 0.001), while there was no change in LVDd. E/A (n = 10) and deceleration time (n = 7), obtained in some patients, did not change significantly (0.89 ± 0.33 to 0.77 ± 0.17%, and 215 ± 46 to 227 ± 72 msec, respectively). In addition, the plasma BNP level was moderately, but significantly decreased from 94 ± 78 to 70 ± 56 pg/mL (P = 0.005). In subgroup analysis, LVEF was improved in both patients with ischemic and nonischemic HF. There was no significant correlation between the percent change in serum total cholesterol and the percent change in LVEF by pitavastatin treatment. Serum total cholesterol, LDL-cholesterol, and triglycerides decreased by 21%, 30%, and 15%, respectively, and HDL-cholesterol increased by 12%. Pitavastatin improved cardiac function in patients with HF, which generally worsens with time. The results suggest that pitavastatin may be beneficial for treatment of HF.

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The impact of guideline adherence on clinical outcomes in the management of chronic heart failure (CHF) has never been evaluated in Japan.
We investigated outcomes in 92 consecutive CHF patients admitted to Kitasato University Hospital in 2004-2006 for HF exacerbation with a left ventricular ejection fraction ≤ 40% by the use of class I drugs for pump-failure, as recommended in the Japanese Circulation Society guideline. Drugs, namely angiotensin-converting enzyme inhibitors (ACEI), beta-blockers (BB), spironolactone, diuretics, and cardiac glycosides were administered to 64.1%, 59.8%, 28.2%, 96.7%, and 68.0% of patients, respectively. Patients for whom adherence to the prescription of ACEI and BB as first-line agents was high had significantly and independently better prognostic outcomes for cardiac events (P = 0.0036) as well as subsequent improvements in clinical surrogate markers for HF status such as NYHA class and BNP. Addition of the 3 latter drugs to the prescription of ACEI and BB did not affect the superiority of ACE plus BB in improving the long-term prognosis.
We have demonstrated that adherence to treatment guidelines for CHF is a significant predictor of subsequent cardiac events in actual practice in Japan. An effective means of improving adherence to current guideline standards of care for CHF has yet to be established.

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Left ventricular (LV) dysfunction generally occurs early in the course of subarachnoid hemorrhage (SAH). We evaluated the prognostic value of electrocardiographic (ECG) abnormalities and echocardiographic LV dysfunction evaluated shortly after SAH.
We prospectively enrolled 47 SAH patients (62 ± 14 years, mean ± SD) who were admitted to the neurosurgical care unit of our institute. Neurological status was rated on the day of admission. Twelve-lead ECG and 2-dimensional echocardiography were recorded 2 ± 1 day after onset of SAH. ECG abnormalities (pathological Q-wave, ST-segment deviation, T-wave inversion, and QT prolongation) were evaluated and the incidences of global (LV ejection fraction < 50%) and segmental (regional wall motion abnormality [RWMA]) LV dysfunction were measured.
During a follow-up period of 44 ± 23 days, 17 (36%) patients died. ECG abnormalities, LV ejection fraction < 50%, and RWMA were observed in 62%, 11%, and 28% of patients, respectively. Univariate Cox proportional hazards regression analysis revealed that neurological status, rate-corrected QT interval, LV ejection fraction, and RWMA were significant predictors of death. After adjustment for these significant clinical variables, and age and sex, independent predictors of mortality were neurological status and RWMA.
RWMA may provide significant prognostic information in patients with SAH.

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The prognostic significance of white coat hypertension (WCH) remains controversial. Consecutive patients (955 cases, 566 females) aged between 15 and 70 years were divided into 3 groups, those with sustained normotension (NT), WCH, and hypertension (HT), and the prevalences of obesity, impaired glucose tolerance (IGT) or type 2 diabetes mellitus (DM), coronary heart disease (CHD), and dyslipidemia were compared among the groups. Although the prevalences of all of the disorders showed significant progression from the sustained NT group towards the WCH and HT groups, the prevalence of dyslipidemia was significantly higher in the WCH group (P < 0.05 for all). Due to the gradually increased prevalences of obesity, IGT or DM, and CHD from the sustained NT group towards the WCH and HT groups and the highest prevalence of dyslipidemia in the WCH group, WCH should preferentially be accepted as an alarming sign of a deterioration in health rather than being a predisposing factor of HT or atherosclerosis alone. The significantly higher prevalence of dyslipidemia in the WCH group than in the HT group may be explained by the increased amount of adipose tissue in the HT cases, since the prevalence of obesity was the highest in the HT group. Thus, the high prevalence of WCH even in early decades may represent increased susceptibility to future weight gain, and dyslipidemia in patients with WCH may be a preliminary sign of obesity. Therefore, the management of WCH should focus on the prevention of dyslipidemia and excess weight gain.

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Angiotensin receptor blockers (ARB) have been emerging as drugs to treat atherosclerosis. The effectiveness of the ARB losartan at reducing atherosclerosis was compared with that of ACE inhibitors in hypertensive patients.
A total of 50 patients with hypertension were divided into 3 groups: a control group receiving neither an ARB nor an ACE inhibitor (n = 14), a losartan group (n = 22) receiving 50 mg/day of losartan, and an ACE inhibitor group (n = 14) receiving either 5 mg/day of enalapril or 5 mg/day of imidapril. Atherosclerosis was evaluated based on the intima-media thickness (IMT) of the common carotid artery measured by B-mode ultrasound at baseline and after approximately 12 months of treatment.
After the treatment, IMT significantly decreased with losartan (from 0.87 ± 0.14 to 0.79 ± 0.16 mm, P < 0.05) and with ACE inhibitor (from 0.81 ± 0.14 to 0.74 ± 0.11 mm, P < 0.05). The reduction was comparable between the two groups, -0.078 ± 0.136 with losartan and -0.073 ± 0.109 mm with ACE inhibitor, and the rate of the reduction was similar between the two drugs; -0.098 ± 0.142 mm/year with losartan and (-0.076 ± 0.118 mm/year) with ACE inhibitor. On the contrary, IMT did not change in the control group (from 0.90 ± 0.20 to 0.95 ± 0.26 mm) during the treatment period. Concomitant medication and coronary risk factors such as hyperlipidemia, diabetes mellitus, and smoking did not differ significantly among the groups.
The antiatherosclerotic effect of losartan on the carotid artery was comparable to that of ACE-inhibitors, and less adverse effects, such as coughing that occurs with ACE inhibitors, were observed. Losartan appears to be a better alternative to ACE inhibitors for treating atherosclerosis in Japanese hypertensive patients.

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4-1BB, a member of the tumor necrosis factor (TNF) receptor superfamily, binds the 4-1BB ligand (4-1BBL) and works as a costimulatory molecule and regulates T cell-mediated immune responses. Because T cell-mediated immunity is associated with graft arterial disease (GAD), we investigated the role of the 4-1BB pathway in the progression of GAD.
Hearts from C57BL/6 mice were transplanted into Bm12 mice (class II mismatch). 4-1BB expression was induced on CD4⁺ and CD8⁺ splenocytes in allografts after cardiac transplantation. 4-1BBL was detected in the vessel wall of the rejecting cardiac allograft and in cultured smooth muscle cells (SMCs) stimulated with fetal calf serum. Recipients were injected intraperitoneally with 4-1BBIg every 7 days for 8 weeks. GAD was significantly attenuated by 4-1BBIg treatment (luminal occlusion, 15.4 ± 3.1% versus control IgG treatment, 75.6 ± 4.6%, P < 0.001). T-cell infiltration of cardiac allografts and expression of interferon-g , interleukin-6, and interleukin-15 in cardiac allografts were suppressed by 4-1BBIg treatment. Coculture of SMCs with sensitized splenocytes after transplantation induced SMC proliferation, and this was inhibited by addition of 4-1BBIg.
The 4-1BB pathway regulates not only T-cell activation but also SMC proliferation. Blockade of the 4-1BB pathway is a promising strategy to prevent progression of GAD.

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A 61-year-old man with prior anteroseptal myocardial infarction (ejection fraction: 40%) presented with recurrent episodes of palpitations. Twelve-lead ECG during palpitations showed an incessant ventricular tachycardia (VT1) with right bundle branch block (RBBB) morphology and inferior axis. Electrophysiologic study revealed that the clinical VT originated from the anterolateral left ventricle. A Purkinje potential preceded onset of the QRS complex by 34 ms. Radiofrequency ablation guided by the Purkinje potential terminated the VT1. Another ventricular tachycardia (VT2) showing RBBB morphology with superior axis and originating from the posteroseptal left ventricle, was induced by programmed ventricular stimulation. A Purkinje potential preceded onset of the local ventricular potential by 120-130 ms in this VT. Radiofrequency ablation guided by the Purkinje potential terminated the VT2.

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A 58-year-old man with atrial fibrillation underwent pulmonary vein (PV) isolation (PVI). Bigeminal atrial premature beats persisted from the beginning of the PVI. The cardiac recordings from a basket catheter (BC) revealed the PV ectopic origin in the distal right superior PV. Successful PVI with the guidance of BC was confirmed by the appearance of concealed ectopy. Surprisingly, the PV ectopy completely disappeared immediately after the successful PVI. The findings suggest that the generation of PV trigger is sometimes dependent on left atrial input and that the underlying mechanism of the PV trigger may have been triggered activity or reentry.

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