1H-MRS to evaluate improved triglyceride accumulation in idiopathic triglyceride deposit cardiomyovasculopathy after CNT-01 (tricaprin/trisdecanion) administration.

Summary: Triglyceride deposit cardiomyovasculopathy (TGCV) is an intractable disease characterized by massive triglyceride (TG) accumulation in the myocardium and coronary arteries caused by genetic or acquired dysfunction of adipose TG lipase (ATGL). A phase IIa trial has been conducted involving patients with idiopathic TGCV using CNT-01 (tricaprin/trisdecanion) by the Japan TGCV study group, which showed that CNT-01 improved myocardial lipolysis as demonstrated by iodine-123-beta-methyl iodophenyl-pentadecanoic acid (BMIPP) scintigraphy. We evaluated changes in myocardial TG content using proton magnetic resonance spectroscopy (1H-MRS) before/after CNT-01. This report describes a male patient with hypertension, diabetes, angina pectoris, repeated percutaneous coronary intervention, chest pain, and exertional dyspnea that persisted despite standard medications and nitroglycerin. Idiopathic TGCV was diagnosed based on a remarkably reduced washout rate (WR) for BMIPP scintigraphy, high myocardial TG content on 1H-MRS, and no ATGL mutation. After an 8-week, 1.5 g/day CNT-01 administration, the WR of BMIPP increased from 5.1 to 13.3% and the myocardial TG content decreased from 8.4 to 5.9%, with no adverse effects. CNT-01 corrected myocardial lipolysis and subsequently reduced TG content in idiopathic TGCV as evaluated using 1H-MRS, which may be a useful, noninvasive evaluation of therapeutic efficacy. Learning points: Triglyceride deposit cardiomyovasculopathy (TGCV) is an intractable disease characterized by massive triglyceride accumulation in the myocardium and coronary arteries, caused by genetic or acquired dysfunction of adipose triglyceride lipase. Japan TGCV Study Group developed a specific treatment for idiopathic TGCV using CNT-01 (tricaprin/trisdecanion), a type of medium-chain fatty acid. CNT-01 corrected myocardial lipolysis and reduced TG content in idiopathic TGCV using proton magnetic resonance spectroscopy, which may be a useful noninvasive evaluation of therapeutic efficacy.

Relationship between coronary high-intensity plaques on T1-weighted imaging by cardiovascular magnetic resonance and vulnerable plaque features by near-infrared spectroscopy and intravascular ultrasound: a prospective cohort study.

BACKGROUND: This study aimed to compare the coronary plaque characterization by cardiovascular magnetic resonance (CMR) and near-infrared spectroscopy (NIRS)-intravascular ultrasound (IVUS) (NIRS-IVUS), and to determine whether pre-percutaneous coronary intervention (PCI) evaluation using CMR identifies high-intensity plaques (HIPs) at risk of peri-procedural myocardial infarction (pMI). Although there is little evidence in comparison with NIRS-IVUS findings, which have recently been shown to identify vulnerable plaques, we inferred that CMR-derived HIPs would be associated with vulnerable plaque features identified on NIRS-IVUS. METHODS: 52 patients with stable coronary artery disease who underwent CMR with non-contrast T1-weighted imaging and PCI using NIRS-IVUS were studied. HIP was defined as a signal intensity of the coronary plaque-to-myocardial signal intensity ratio (PMR) ≥ 1.4, which was measured from the data of CMR images. We evaluated whether HIPs were associated with the NIRS-derived maximum 4-mm lipid-core burden index (maxLCBI4mm) and plaque morphology on IVUS, and assessed the incidence and predictor of pMI defined by the current Universal Definition using high-sensitive cardiac troponin-T. RESULTS: Of 62 lesions, HIPs were observed in 30 lesions (48%). The HIP group had a significantly higher remodeling index, plaque burden, and proportion of echo-lucent plaque and maxLCBI4mm ≥ 400 (known as large lipid-rich plaque [LRP]) than the non-HIP group. The correlation between the maxLCBI4mm and PMR was significantly positive (r = 0.51). In multivariable logistic regression analysis for prediction of HIP, NIRS-derived large LRP (odds ratio [OR] = 5.41; 95% confidence intervals [CIs] 1.65-17.8, p = 0.005) and IVUS-derived echo-lucent plaque (OR = 5.12; 95% CIs 1.11-23.6, p = 0.036) were strong independent predictors. Furthermore, pMI occurred in 14 of 30 lesions (47%) with HIP, compared to only 5 of 32 lesions (16%) without HIP (p = 0.005). In multivariable logistic regression analysis for prediction of incidence of pMI, CMR-derived HIP (OR = 5.68; 95% CIs 1.53-21.1, p = 0.009) was a strong independent predictor, but not NIRS-derived large LRP and IVUS-derived echo-lucent plaque. CONCLUSIONS: There is an important relationship between CMR-derived HIP and NIRS-derived large LRP. We also confirmed that non-contrast T1-weighted CMR imaging is useful for characterization of vulnerable plaque features as well as for pre-PCI risk stratification. Trial registration The ethics committee of Juntendo Clinical Research and Trial Center approved this study on January 26, 2021 (Reference Number 20-313).

Triglyceride Deposit Cardiomyovasculopathy with Massive Myocardial Triglyceride which Was Proven Using Proton-magnetic Resonance Spectroscopy.

The patient was a 73-year-old man with a history of hypertension, diabetes mellitus, dyslipidemia, rheumatoid arthritis, repeated percutaneous coronary intervention and percutaneous peripheral intervention procedures. He was frequently admitted to our hospital for congestive heart failure with orthopnea. The myocardial washout rate of iodine-123-ß-methyl iodophenyl-pentadecanoic acid was defective on scintigraphy. He was diagnosed with triglyceride deposit cardiomyovasculopathy (TGCV). Proton magnetic resonance spectroscopy (1H-MRS) indicated the level of myocardial triglyceride (TG) content to be extremely high (4.92%). This is the first report to confirm a massive accumulation of TG in the myocardium of a patient with TGCV using 1H-MRS noninvasively.

Preliminary Pilot Study of Combined Effects of Physical Activity and Achievement of LDL-Cholesterol Target on Coronary Plaque Volume Changes in Patients with Acute Coronary Syndrome.

BACKGROUND: We investigated the combined effects of physical activity (PA) and aggressive low-density lipoprotein cholesterol (LDL-C) reduction on the changes in coronary plaque volume (PV) in patients with acute coronary syndrome (ACS) using volumetric intravascular ultrasound (IVUS) analysis. METHODS: We retrospectively analyzed data from two different prospective clinical trials that involved 101 ACS patients who underwent percutaneous coronary intervention (PCI) and assessed the non-culprit sites of PCI lesions using IVUS at baseline and at the follow-up. After PCI, all the patients participated in early phase II comprehensive cardiac rehabilitation. Patients were divided into four groups based on whether the average daily step count, measured using a pedometer, was 7000 steps of more and whether the follow-up LDL-C level was <70 mg/dL. At the time of follow-up, we examined the correlation of changes in the PV with LDL-C and PA. RESULTS: The baseline characteristics of the four study groups were comparable. At the follow-up, plaque regression in both the achievement group (PA and LDL-C reduction) was higher than that in the other three groups. In addition, plaque reduction independently correlated with increased PA and reduction in LDL-C level. CONCLUSIONS: Combined therapy of intensive PA and achievement of LDL-C target retarded coronary PV in patients with ACS.

A Simple Skin Incision Design for Pediatric Superficial Branch of Superficial Circumflex Iliac Artery.

BACKGROUND: Superficial circumflex iliac artery (SCIA) perforator flap is one of the demanding flaps. However, little is known about SCIA anatomy, which is crucial for successful SCIA perforator flap elevation, in children. We assessed the efficacy of our incision design to detect the superficial branch of the SCIA in vivo. METHODS: Eleven consecutive pediatric patients who required harvesting (eg, skin grafts or vascularized lymph node transfer) were assessed. All possible congenital vascular malformation cases were excluded. To reduce potential bias, all groin procedures were performed on the contralateral side of malformations. After inguinal area mapping, 1.5-cm skin incision was made. From the window opened by the skin incision, tiny perforation to the skin surface was detected for further dissection. Following the tiny branch, the main trunk of the superficial circumflex vascular bundle was dissected. The whole vascular bundle, artery, and major vein from the bundle were dissected and their sizes were measured. RESULTS: Of the 11 patients, 4 were boys; the age range was 5 months to 14 years (mean age: 3.2 years). Vessel bundle size was 0.7-1.5 (mean: 1.1 mm). In all cases, the bundle was detected within 5 min (1-5, mean: 2.5 min). No vascular damage was observed, and all arteries pulsated well, without requiring additional skin incision. The superficial branch of the SCIA was mainly detected right below the initial skin incision. CONCLUSIONS: Our skin incision design can effectively detect the SCIA in pediatric patients and may be used in adult patients.

Clinical significance of non-culprit plaque regression following acute coronary syndrome: A serial intravascular ultrasound study.

BACKGROUND: The use of serial intravascular ultrasound (IVUS) for coronary atherosclerosis has offered valuable insight into plaque regression (PR) or progression. However, the beneficial effects of PR on the long-term clinical outcomes in patients with acute coronary syndrome (ACS) remain unclear. We aimed to evaluate the impact of coronary plaque change in patients following primary percutaneous coronary intervention. METHODS: We retrospectively analyzed data from 4 prospective clinical trials involving 173 patients with ACS who underwent serial IVUS of non-culprit lesions on statin treatment at baseline and at 6 or 8 months of follow-up. The relationship of the IVUS findings with the change in percent atheroma volume (PAV), on-treatment low-density lipoprotein cholesterol (LDL-C), and major adverse cardiac and cerebrovascular events (MACCE) were investigated. RESULTS: In our serial IVUS analysis, baseline plaque volume and PAV were 79.6mm3 and 46.0%, respectively. The overall change in PAV was -1.5% [interquartile range (IQR): -4.1% to 1.0%], and PR (i.e. PAV change from baseline <0) was observed in 67.1% of patients. They were followed up observationally for a mean of 3.5 years and a total of 37 MACCE occurred. The rate of MACCE tended to be lower in patients with PR than in those without PR (18.1% vs. 28.7%, p=0.14). A multivariate Cox hazard model analysis demonstrated that achievement of both PR and on-treatment low LDL-C levels (<70mg/dL) was the only significant independent predictor of MACCE (hazard ratio: 0.42, 95% confidence interval: 0.19-0.88; p=0.02). CONCLUSIONS: Achievement of both PR and sufficient lowering of the LDL-C was clinically important in post-ACS management.

Usefulness of Cardiac Magnetic Resonance in the Diagnosis of Löffler Endocarditis Secondary to Eosinophilic Granulomatosis with Polyangiitis.

A 40-year-old man who was diagnosed with bronchial asthma and eosinophilia was transferred to our hospital due to a worsening respiratory status. He was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA), and eosinophilic pneumoniae. Cardiac magnetic resonance (CMR) imaging indicated Löffler endocarditis. Treatment was initiated using intravenous methylprednisolone, cyclophosphamide, and heparin as anticoagulation therapy. Three months later, CMR showed the improvement of the LV myocardium. In this case, the early diagnosis of Löffler endocarditis by CMR could prevent systemic embolism and CMR was useful for assessing the curative effects of steroid and immunosuppressant therapy.

Impact of Physical Activity on Coronary Plaque Volume and Components in Acute Coronary Syndrome Patients After Early Phase II Cardiac Rehabilitation.

BACKGROUND: Cardiac rehabilitation (CR) is an established multidisciplinary secondary preventive program. We investigated the effects of CR involving intensive physical activity (PA) on coronary plaque volume and components in patients with acute coronary syndrome (ACS).Methods and Results:We enrolled 32 consecutive patients with ACS in early phase II CR and randomly assigned them to an intensive CR group (n=18; CR participation ≥twice/week, daily PA ≥9,000 steps) or a standard CR group (n=14; CR participation ≥once/2weeks, daily PA ≥6,000 steps). Serial integrated backscatter intravascular ultrasound was performed for non-culprit lesions at baseline and after 8 months. Baseline clinical data were identical between the 2 groups. Unexpectedly, CR participation and PA did not differ significantly between the 2 groups, and there was no significant difference in plaque volume (PV) or components between the 2 groups. Subsequently, we classified the patients into 2 groups according to median PA (7,000 steps). There were significant differences in percent change of PV and of lipid volume between these 2 groups. In addition, these changes were negatively and independently correlated with PA. CONCLUSIONS: No significant difference was observed in PV or components between the intensive CR and the standard CR groups. Intensive PA, however, may retard coronary PV and ameliorate lipid component in patients with ACS participating in late phase II CR.

Video Super-microsurgery Amplified using Close-up Lens Filter on the Operative Field Camera: Preliminary Report.

BACKGROUND: Super-microsurgery has widely spread due to the improvement of high magnification microscopes. The cost of multiple microscopes is high. Furthermore, the microscope heads are too large to fit in multiple surgical fields for pediatric patients. We adapted a 2-dimensional magnification system for performing lymphatic venous anastomosis on pediatric lymphedema cases. METHODS: We attached a close-up lens filter to the suspended camera (CHZ-1,360-PTR camera, Carina system, Tokyo, Japan) in the operative field. This was done to achieve 26× magnification using a small camera head, making it possible to perform super-micro anastomoses. Anastomoses time, scar length, and lymph vessel diameters were measured, and the outcomes were statistically analyzed and compared with the contralateral side. RESULTS: Four pediatric lymphedema patients underwent the aforementioned technique, using the multisite microscopic approach. All anastomoses were completed within 20 minutes. The results were not significantly different from the conventional microscopic lymphatic venous anastomosis. CONCLUSION: This system is advantageous because (1) it has less costly initial investments; (2) it requires a small camera head, which provides available space for the multisite microscopic approach even for pediatric patients; and (3) it allows for a wider surgical working space.

Cleft Lip and Palate Repair Using a Surgical Microscope.

BACKGROUND: Cleft lip and palate repair requires a deep and small surgical field and is usually performed by surgeons wearing surgical loupes. Surgeons with loupes can obtain a wider surgical view, although headlights are required for the deepest procedures. Surgical microscopes offer comfort and a clear and magnification-adjustable surgical site that can be shared with the whole team, including observers, and easily recorded to further the education of junior surgeons. Magnification adjustments are convenient for precise procedures such as muscle dissection of the soft palate. METHODS: We performed a comparative investigation of 18 cleft operations that utilized either surgical loupes or microscopy. Paper-based questionnaires were completed by staff nurses to evaluate what went well and what could be improved in each procedure. The operating time, complication rate, and scores of the questionnaire responses were statistically analyzed. RESULTS: The operating time when microscopy was used was not significantly longer than when surgical loupes were utilized. The surgical field was clearly shared with surgical assistants, nurses, anesthesiologists, and students via microscope-linked monitors. Passing surgical equipment was easier when sharing the surgical view, and preoperative microscope preparation did not interfere with the duties of the staff nurses. CONCLUSIONS: Surgical microscopy was demonstrated to be useful during cleft operations.

Myocardial triglyceride content in patients with left ventricular hypertrophy: comparison between hypertensive heart disease and hypertrophic cardiomyopathy.

Proton magnetic resonance spectroscopy (1H-MRS) enables the assessment of myocardial triglyceride (TG) content, which is reported to be associated with cardiac dysfunction and morphology accompanied by metabolic disorder and cardiac hemodynamic status. The clinical usefulness of myocardial TG content measurements in patients with left ventricular hypertrophy (LVH) has not been fully investigated. We examined whether myocardial TG content assessed by 1H-MRS was useful for diagnosis in patients with LVH. To quantify myocardial TG content, we conducted 1H-MRS in 35 subjects with LVH. Left ventricular function was measured by cardiac magnetic resonance imaging. Patients were assigned to a hypertensive heart disease (HHD, n = 10) or hypertrophic cardiomyopathy (HCM, n = 25) group based on the histology and/or late gadolinium enhancement pattern. The myocardial TG content was significantly higher in the HHD group than in the HCM group (2.14 ± 1.29 vs. 1.09 ± 0.72 %, P < 0.001). Myocardial TG content were significantly and negatively correlated with LV mass (r = -0.41, P < 0.04) and stroke volume (r = -0.64, P < 0.05) in the HCM group and HHD group, respectively. In a multivariate analysis, LV mass volume and diagnosis of HCM or HHD were independent factors of the myocardial TG content. The results suggest that myocardial metabolism may differ between HCM and HHD patients and that measurement of myocardial TG content by 1H-MRS may be useful for evaluating the myocardial metabolic features of LVH.

Effect of sitagliptin on plaque changes in coronary artery following acute coronary syndrome in diabetic patients: The ESPECIAL-ACS study.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have anti-atherosclerotic and cardioprotective effects in vitro. However, the impact of DPP-4 inhibitors on coronary plaque remains unclear. We sought to assess the effect of sitagliptin on coronary plaque volume (PV) and stabilization in diabetic patients with acute coronary syndrome (ACS). METHODS: The ESPECIAL-ACS was a prospective, randomized, open-label, parallel group study at 4 Japanese centers to assess the effect of 6-month treatment with sitagliptin on coronary plaque changes in non-culprit lesion in diabetic patients with ACS using serial intravascular ultrasound (IVUS) and integrated backscatter IVUS (IB-IVUS) analysis. RESULTS: A total of 41 patients were randomly allocated to either sitagliptin group (diet and exercise with sitagliptin 50-100mg daily, n=21) or control group (diet and exercise, n=20) within 72h after percutaneous coronary intervention, and underwent volumetric IVUS and IB-IVUS analyses at baseline and 6-month follow-up. At 6-month follow-up, the percent change in PV as primary endpoint was larger in the sitagliptin group than in the control group, but the difference was not statistically significant (-4.0±8.5% vs. -1.4±8.8%, p=0.35). In IB-IVUS analysis, the percent change in lipid PV significantly decreased in the sitagliptin group compared with the control group (-7.1±21.5% vs. 15.6±41.8%, p=0.03). CONCLUSIONS: Compared with diet and exercise therapy, sitagliptin did not significantly reduce coronary PV in diabetic patients with ACS at 6-month follow-up. However, the percent change in lipid PV significantly decreased in the sitagliptin group, suggesting that sitagliptin has a potential to stabilize the plaque vulnerability.

Evaluation of myocardial triglyceride accumulation assessed on 1H-magnetic resonance spectroscopy in apparently healthy Japanese subjects.

OBJECTIVE: Proton magnetic resonance spectroscopy ((1)H-MRS) enables the clinician to noninvasively assess the amount of ectopic fat in the liver, skeletal muscle and myocardium. Recent studies have reported that the myocardial triglyceride (TG) content is associated with aging, metabolic disorders and cardiac dysfunction. However, the clinical usefulness of myocardial TG measurements in Japanese subjects has not been fully investigated. METHODS: The myocardial TG content was evaluated using (1)H-MRS in 37 apparently healthy Japanese subjects, and the left ventricular function was measured on cardiac magnetic resonance imaging (MRI). Blood pressure, body composition and biochemical markers were measured in a fasting state, and cardiopulmonary exercise testing (CPX) was performed to evaluate exercise capacity. RESULTS: The mean myocardial TG content was 0.85±0.40%. The myocardial TG content was significantly associated with the percent body fat (r=0.39), serum triglyceride level (r=0.40), estimated glomerular filtration rate (r=-0.37), anaerobic threshold (r=-0.36), maximal load of CPX (r=0.39), left ventricular end-diastolic volume (r=-0.41) and left ventricular end-systolic volume (LVESV) (r=-0.51) (all: p<0.05). In a multivariate analysis, the LVESV was found to be an independent factor of the myocardial TG content. CONCLUSION: (1)H-MRS may be useful for assessing the associations between the myocardial TG content and various clinical parameters, including those reflecting obesity, metabolic disorders, cardiac morphology and exercise capacity, noninvasively, even in Japanese subjects.

Circulating soluble LR11, a novel marker of smooth muscle cell proliferation, is enhanced after coronary stenting in response to vascular injury.

OBJECTIVE: Restenosis after vascular intervention remains a major clinical problem. Circulating LR11 has been shown a novel marker of intimal smooth muscle cell (SMC) proliferation in human and animal studies. The present study was performed to clarify the clinical significance of circulating LR11 in patients with stable angina pectoris after coronary stenting. METHODS AND RESULTS: We firstly investigated the circulating sLR11 levels for 28 days after arterial injury in mice, and then assessed time-dependent change in circulating sLR11 level after coronary stenting in a clinical study. Mouse sLR11 levels rapidly increased to 4.0-fold of the control value without cuff placement at postoperative day (POD) 14, and the levels gradually declined to 3.1-fold of the control value until POD 28 in mice. The circulating soluble LR11 levels were measured (before and at 14, 60 and 240 days after coronary stenting in a clinical study of 102 consecutive patients with stable angina pectoris who were treated with percutaneous coronary intervention. Circulating sLR11 levels were significantly increased on days 14 and 60 after the procedure and positively associated with the angiographic late loss index. CONCLUSIONS: Our study suggested that circulating sLR11 levels may be a potential marker for angiographic late loss in patients after coronary stenting. Further mechanistic studies are expected to know the clinical significance of sLR11 as a novel marker for intimal SMC.

Low high-density lipoprotein cholesterol is a residual risk factor associated with long-term clinical outcomes in diabetic patients with stable coronary artery disease who achieve optimal control of low-density lipoprotein cholesterol.

Diabetes mellitus is recognized an independent risk factor for coronary artery disease (CAD) and mortality. Clinical trials have shown that statins significantly reduce cardiovascular events in diabetic patients. However, residual cardiovascular risk persists despite the achievement of target low-density lipoprotein cholesterol (LDL-C) levels with statin. High-density lipoprotein cholesterol (HDL-C) is an established coronary risk factor that is independent of LDL-C levels. We evaluated the impact of HDL-C on long-term mortality in diabetic patients with stable CAD who achieved optimal LDL-C. We enrolled 438 consecutive diabetic patients who were scheduled for percutaneous coronary intervention between 2004 and 2007 at our institution. We identified 165 patients who achieved target LDL-C <100 mg/dl. Patients were stratified into two groups according to HDL-C levels (low HDL-C group, baseline HDL-C <40 mg/dl; high HDL-C group, ≥40 mg/dl). Major adverse cardiac events (MACE) that included all-cause death, acute coronary syndrome, and target lesion revascularization were evaluated between the two groups. The median follow-up period was 946 days. The rate of MACE was significantly higher in diabetic patients with low-HDL-C who achieved optimal LDL-C (6.9 vs 17.9 %, log-rank P = 0.030). Multivariate Cox regression analysis showed that HDL-C is significantly associated with clinical outcomes (adjusted hazard ratio for MACE 1.33, 95 % confidence interval 1.01-1.75, P = 0.042). Low HDL-C is a residual risk factor that is significantly associated with long-term clinical outcomes among diabetic patients with stable CAD who achieve optimal LDL-C levels.

Association between myocardial triglyceride content and cardiac function in healthy subjects and endurance athletes.

Ectopic fat accumulation plays important roles in various metabolic disorders and cardiovascular diseases. Recent studies reported that myocardial triglyceride (TG) content measured by proton magnetic resonance spectroscopy ((1)H-MRS) is associated with aging, diabetes mellitus, and cardiac dysfunction. However, myocardial TG content in athletes has not yet been investigated. We performed (1)H-MRS and cardiac magnetic resonance imaging in 10 male endurance athletes and 15 healthy male controls. Serum markers and other clinical parameters including arterial stiffness were measured. Cardiopulmonary exercise testing was also performed. There were no significant differences in clinical characteristics including age, anthropometric parameters, blood test results, or arterial stiffness between the two groups. Peak oxygen uptakes, end-diastolic volume (EDV), end-systolic volume (ESV), left ventricular (LV) mass, peak ejection rates and peak filling rates were significantly higher in the athlete group than in the control group (all P<0.02). Myocardial TG content was significantly lower in the athlete group than in the control group (0.60 ± 0.20 vs. 0.89 ± 0.41%, P<0.05). Myocardial TG content was negatively correlated with EDV (r = -0.47), ESV (r = -0.64), LV mass (r = -0.44), and epicardial fat volume (r = 0.47) (all P<0.05). In conclusion, lower levels of myocardial TG content were observed in endurance athletes and were associated with morphological changes related to physiological LV alteration in athletes, suggesting that metabolic imaging for measurement of myocardial TG content by (1)H-MRS may be a useful technique for noninvasively assessing the "athlete's heart".

Japanese features of native valve endocarditis caused by coagulase-negative staphylococci: case reports and a literature review.

Although coagulase-negative staphylococci (CoNS) is a frequent cause of prosthetic valve endocarditis, native valve endocarditis (NVE) caused by CoNS is not commonly seen. Its high mortality is well known; however, there are no systematic reports published in Japan. We herein report the cases of two Japanese patients with CoNS NVE who were admitted to our hospital located in Tokyo and conduct literature searches on CoNS NVE in Japan from 1983 to March 2012 using PubMed and ICHUSHI WEB (Japan Medical Abstract Society). We also summarize the features of 22 Japanese patients with CoNS NVE, including our patients.

Increased circulating soluble LR11 in patients with acute coronary syndrome.

BACKGROUND: LR11 (also so called SorLA or SORL1) is a novel marker of intimal smooth muscle cell (SMC) proliferation. Vascular SMCs play important roles in the development of atherosclerosis interacting with macrophages in a vulnerable plaque of patients with acute coronary syndrome (ACS).The present study determines whether soluble LR11 (sLR11) is associated with ACS. METHODS: We studied 100 patients with coronary artery disease (CAD) comprising 50 consecutive patients with acute coronary syndrome (ACS; mean age 62.3±13.0 years; male 78.0%) who were successfully treated with percutaneous coronary intervention and 50 age- and sex-matched stable angina pectoris (SAP) patients as control. Concentration of sLR11 was measured by sandwich enzyme-linked immunosorbent assay method. RESULTS: Circulating sLR11 was significantly increased in patients with ACS compared with SAP (9.88±2.78 vs. 8.18±1.11 ng/ml, p<0.01). Multivariate logistic regression analysis indicated that sLR11 was independently associated with ACS (odds ratio (OR), sLR11 quartile increment, 2.18, 95% confidence interval (CI) 1.21-4.19, p<0.01). Among various biomarkers of acute coronary syndrome, hsCRP were significantly correlated with LR11 (r=0.480, p<0.01). CONCLUSIONS: There is a statistical significant association between LR11 and ACS and may be a useful biomarker for the development of acute coronary syndrome.

Impact of red blood cell distribution width on long-term mortality in diabetic patients after percutaneous coronary intervention.

BACKGROUND: Red blood cell distribution width (RDW) is a novel prognostic marker that reflects oxidative stress and chronic inflammation in patients with cardiovascular disease. Diabetes mellitus increases oxidative stress and vascular inflammation, which accelerate atherosclerosis. However, the relationship between RDW and long-term outcome in diabetic patients with coronary artery disease (CAD) is unclear. METHODS AND RESULTS: Subjects comprised 560 consecutive diabetic patients (mean age, 66.6 years; male, 80%) with stable CAD who had undergone elective percutaneous coronary intervention (PCI). Patients were divided into 2 groups according to median RDW at baseline (13.1%): a high RDW group (mean RDW, 14.0%; interquartile range, 13.3-14.2%); and a low RDW group (mean RDW, 12.6%; interquartile range, 12.4-12.9%). All-cause mortality rates were compared between groups. Mean duration of follow up was 3.9 years. Patients with high RDW were more likely to be older, show dyslipidemia and have a lower ejection fraction and decreased hemoglobin level. Twenty-nine patients (5.2%) died during follow up. The cumulative incidence of all-cause death was significantly higher in the high RDW group than in the low RDW group (log-rank P=0.0015). Multivariate analysis identified high RDW as being associated with all-cause mortality (hazard ratio, 2.56; 95% confidence interval, 1.12-6.62; P=0.025). CONCLUSIONS: Increased RDW was significantly associated with increased long-term all-cause mortality in diabetic patients after PCI.