Recent advances regarding the potential roles of invariant natural killer T cells in cardiovascular diseases with immunological and inflammatory backgrounds.

Invariant natural killer T (iNKT) cells, which bear αß-type T cell antigen-receptors, recognize glycolipid antigens in a cluster of differentiation 1d (CD1d)-restricted manner. Regarding these cells, the unique modes of thymic selection and maturation elucidate innateness, irrespective of them also being members of the adaptive immune system as a T cell. iNKT cells develop and differentiate into NKT1 [interferon γ (IFN-γγ-producing], NKT2 [interleukin 4 (IL-4)/IL-13-producing], or NKT17 (IL-17-producing) subsets in the thymus. After egress, NKT10 (IL-10-producing), follicular helper NKT (NKTfh; IL-21-producing), and regulatory NKT (NKTreg) subsets emerge following stimulation in the periphery. Moreover, iNKT cells have been shown to possess several physiological or pathological roles. iNKT cells exhibit dual alleviating or aggravating roles in experimentally induced immune and/or inflammatory diseases in mice. These findings indicate that the modulation of iNKT cells can be employed for therapeutic use or prevention of human diseases. In this review, we discuss the potential roles of iNKT cells in the development of immune/inflammatory diseases of the cardiovascular system, with emphasis on atherosclerosis, aortic aneurysms, and cardiac remodeling.

The AppCare-HF randomized clinical trial: a feasibility study of a novel self-care support mobile app for individuals with chronic heart failure.

Aims: We evaluated a self-care intervention with a novel mobile application (app) in chronic heart failure (HF) patients. To facilitate patient-centred care in HF management, we developed a self-care support mobile app to boost HF patients' optimal self-care. Methods and results: We conducted a multicentre, randomized, controlled study evaluating the feasibility of the self-care support mobile app designed for use by HF patients. The app consists of a self-monitoring assistant, education, and automated alerts of possible worsening HF. The intervention group received a tablet personal computer (PC) with the self-care support app installed, and the control group received a HF diary. All patients performed self-monitoring at home for 2 months. Their self-care behaviours were evaluated by the European Heart Failure Self-Care Behaviour Scale. We enrolled 24 outpatients with chronic HF (ages 31-78 years; 6 women, 18 men) who had a history of HF hospitalization. During the 2 month study period, the intervention group (n = 13) showed excellent adherence to the self-monitoring of each vital sign, with a median [interquartile range (IQR)] ratio of self-monitoring adherence for blood pressure, body weight, and body temperature at 100% (92-100%) and for oxygen saturation at 100% (91-100%). At 2 months, the intervention group's self-care behaviour score was significantly improved compared with the control group (n = 11) [median (IQR): 16 (16-22) vs. 28 (20-36), P = 0.02], but the HF Knowledge Scale, the General Self-Efficacy Scale, and the Short Form-8 Health Survey scores did not differ between the groups. Conclusion: The novel mobile app for HF is feasible.

Enhanced mitochondrial oxidative metabolism in peripheral blood mononuclear cells is associated with fatty liver in obese young adults.

Systemic inflammation underlies the association between obesity and nonalcoholic fatty liver disease (NAFLD). Here, we investigated functional changes in leukocytes' mitochondria in obese individuals and their associations with NAFLD. We analyzed 14 obese male Japanese university students whose body mass index was > 30 kg/m2 and 15 healthy age- and sex-matched lean university students as controls. We observed that the mitochondrial oxidative phosphorylation (OXPHOS) capacity with complex I + II-linked substrates in peripheral blood mononuclear cells (PBMCs), which was measured using a high-resolution respirometry, was significantly higher in the obese group versus the controls. The PBMCs' mitochondrial complex IV capacity was also higher in the obese subjects. All of the obese subjects had hepatic steatosis defined by a fatty liver index (FLI) score ≥ 60, and there was a positive correlation between their FLI scores and their PBMCs' mitochondrial OXPHOS capacity. The increased PBMCs' mitochondrial OXPHOS capacity was associated with insulin resistance, systemic inflammation, and higher serum levels of interleukin-6 in the entire series of subjects. Our results suggest that the mitochondrial respiratory capacity is increased in the PBMCs at the early stage of obesity, and the enhanced PBMCs' mitochondrial oxidative metabolism is associated with hepatic steatosis in obese young adults.

Natural Killer T Cells Are Involved in Atherosclerotic Plaque Instability in Apolipoprotein-E Knockout Mice.

The infiltration and activation of macrophages as well as lymphocytes within atherosclerotic lesion contribute to the pathogenesis of plaque rupture. We have demonstrated that invariant natural killer T (iNKT) cells, a unique subset of T lymphocytes that recognize glycolipid antigens, play a crucial role in atherogenesis. However, it remained unclear whether iNKT cells are also involved in plaque instability. Apolipoprotein E (apoE) knockout mice were fed a standard diet (SD) or a high-fat diet (HFD) for 8 weeks. Moreover, the SD- and the HFD-fed mice were divided into two groups according to the intraperitoneal injection of α-galactosylceramide (αGC) that specifically activates iNKT cells or phosphate-buffered saline alone (PBS). ApoE/Jα18 double knockout mice, which lack iNKT cells, were also fed an SD or HFD. Plaque instability was assessed at the brachiocephalic artery by the histological analysis. In the HFD group, αGC significantly enhanced iNKT cell infiltration and exacerbated atherosclerotic plaque instability, whereas the depletion of iNKT cells attenuated plaque instability compared to PBS-treated mice. Real-time PCR analyses in the aortic tissues showed that αGC administration significantly increased expressional levels of inflammatory genes such as IFN-γ and MMP-2, while the depletion of iNKT cells attenuated these expression levels compared to those in the PBS-treated mice. Our findings suggested that iNKT cells are involved in the exacerbation of plaque instability via the activation of inflammatory cells and upregulation of MMP-2 in the vascular tissues.

Activation of Invariant Natural Killer T Cells by α-Galactosylceramide Attenuates the Development of Angiotensin II-Mediated Abdominal Aortic Aneurysm in Obese ob/ob Mice.

The infiltration and activation of macrophages as well as lymphocytes within the aorta contribute to the pathogenesis of abdominal aortic aneurysm (AAA). Invariant natural killer T (iNKT) cells are unique subset of T lymphocytes and have a crucial role in atherogenesis. However, it remains unclear whether iNKT cells also impact on the development of AAA. Ob/ob mice were administered angiotensin II (AngII, 1,000 ng/kg/min) or phosphate-buffered saline (PBS) by osmotic minipumps for 4 weeks and further divided into 2 groups; α-galactosylceramide (αGC; PBS-αGC; n = 5 and AngII-αGC; n = 12), which specifically activates iNKT cells, and PBS (PBS-PBS; n = 10, and AngII-PBS; n = 6). Maximal abdominal aortic diameter was comparable between PBS-PBS and PBS-αGC, and was significantly greater in AngII-PBS than in PBS-PBS. This increase was significantly attenuated in AngII-αGC without affecting blood pressure. αGC significantly enhanced iNKT cell infiltration compared to PBS-PBS. The ratio of F4/80-positive macrophages or CD3-positive T lymphocytes area to the lesion area was significantly higher in AngII-PBS than in PBS-PBS, and was significantly decreased in AngII-αGC. Gene expression of M2-macrophage specific markers, arginase-1 and resistin-like molecule alpha, was significantly greater in aortic tissues from AngII-αGC compared to AngII-PBS 1 week after AngII administration, and this increase was diminished at 4 weeks. Activation of iNKT cells by αGC can attenuate AngII-mediated AAA in ob/ob mice via inducing anti-inflammatory M2 polarized state. Activation of iNKT cells by the bioactive lipid αGC may be a novel therapeutic target against the development of AAA.

The disruption of invariant natural killer T cells exacerbates cardiac hypertrophy and failure caused by pressure overload in mice.

NEW FINDINGS: What is the central question of this study? We questioned whether the disruption of invariant natural killer T (iNKT) cells exacerbates left ventricular (LV) remodelling and heart failure after transverse aortic constriction in mice. What are the main findings and their importance? Pressure overload induced by transverse aortic constriction increased the infiltration of iNKT cells in mouse hearts. The disruption of iNKT cells exacerbated LV remodelling and hastened the transition from hypertrophy to heart failure, in association with the activation of mitogen-activated protein kinase signalling. Activation of iNKT cells modulated the immunological balance in this process and played a protective role against LV remodelling and failure. ABSTRACT: Chronic inflammation is involved in the development of cardiac remodelling and heart failure (HF). Invariant natural killer T (iNKT) cells, a subset of T lymphocytes, have been shown to produce various cytokines and orchestrate tissue inflammation. The pathophysiological role of iNKT cells in HF caused by pressure overload has not been studied. In the present study, we investigated whether the disruption of iNKT cells affected this process in mice. Transverse aortic constriction (TAC) and a sham operation were performed in male C57BL/6J wild-type (WT) and iNKT cell-deficient Jα18 knockout (KO) mice. The infiltration of iNKT cells was increased after TAC. The disruption of iNKT cells exacerbated left ventricular (LV) remodelling and hastened the transition to HF after TAC. Histological examinations also revealed that the disruption of iNKT cells induced greater myocyte hypertrophy and a greater increase in interstitial fibrosis after TAC. The expressions of interleukin-10 and tumour necrosis factor-α mRNA and their ratio in the LV after TAC were decreased in the KO compared with WT mice, which might indicate that the disruption of iNKT cells leads to an imbalance between T-helper type 1 and type 2 cytokines. The phosphorylation of extracellular signal-regulated kinase was significantly increased in the KO mice. The disruption of iNKT cells exacerbated the development of cardiac remodelling and HF after TAC. The activation of iNKT cells might play a protective role against HF caused by pressure overload. Targeting the activation of iNKT cells might thus be a promising candidate as a new therapeutic strategy for HF.

Mitochondrial reactive oxygen species generation in blood cells is associated with disease severity and exercise intolerance in heart failure patients.

Systemic oxidative stress plays a key role in the development of chronic heart failure (CHF). We tested the hypothesis that mitochondrial reactive oxygen species (ROS) generation in circulating peripheral blood mononuclear cells (PBMCs) contributes to CHF progression. A total of 31 patients who had a history of hospital admission due to worsening HF were enrolled and grouped as having either mild CHF defined as New York Heart Association (NYHA) functional class I-II or moderate-to-severe CHF defined as NYHA functional class III. ROS levels in PBMC mitochondria were significantly increased in CHF patients with NYHA functional class III compared to those with NYHA functional class I-II, accompanied by impaired mitochondrial respiratory capacity in PBMCs. ROS generation in PBMC mitochondria was positively correlated with urinary 8-hydroxydeoxyguanosine, a systemic oxidative stress marker, in CHF patients. Importantly, mitochondrial ROS generation in PBMCs was directly correlated with plasma levels of B-type natriuretic peptide, a biomarker for severity of HF, and inversely correlated with peak oxygen uptake, a parameter of exercise capacity, in CHF patients. The study showed that ROS generation in PBMC mitochondria was higher in patients with advanced CHF, and it was associated with disease severity and exercise intolerance in CHF patients.

[The clinical condition and treatment of diseases associated with sudden death].

The Hokkaido Medical Society is a group of doctors and medical researchers in Hokkaido. Its purpose is to contribute to medicine and to the improvement of medical treatment. This symposium was carried out in order to inform citizens about the condition known as sudden death. We hypothesize that the incidence of sudden death tends to increase in line with the incidence of metabolic syndrome. Approximately four hundred patients were transported to our hospital by ambulance in a state of cardiopulmonary arrest (CPA) last year. The number of CPA patients who are treated in our hospital has increased in comparison to the previous decade. The theme of this year is "The clinical condition and treatment of diseases associated with sudden death" in view of the above mentioned situation. In 2015, it was reported that sudden death occurred in an American pilot and that the co-pilot was forced to make an emergency landing. Interestingly, sudden death can ever sometimes occur in pilots who undergo regular physical examinations. Numerous diseases and conditions are associated with sudden death, including: acute myocardial infarction, irregular pulse, cardiac insufficiency, cerebrovascular disease, aortic dissection and choking. We are of the opinion that the frequency of sudden death is very high in the fields of emergency medicine, cardiovascular medicine, cardiovascular surgery and neurosurgery. In this symposium, we presented and explained the condition that is known as sudden death and the current state of treatment of sudden death in emergency medicine, cardiovascular medicine, cardiovascular surgery and neurosurgery departments of the Hokkaido University Graduate School of Medicine in October, 2015. We hope that the symposium will help the citizen audience to understand the condition and treatment of sudden death, and also to help prevent sudden death.

AST-120 ameliorates lowered exercise capacity and mitochondrial biogenesis in the skeletal muscle from mice with chronic kidney disease via reducing oxidative stress.

BACKGROUND: Exercise capacity and quality of life are markedly impaired in chronic kidney disease (CKD). Increased plasma uremic toxins such as indoxyl sulfate (IS), which induce oxidative stress, may be involved in this process. An oral adsorbent, AST-120, can reduce circulating IS, however, its effects on skeletal muscle and exercise capacity have not been investigated in CKD. METHODS: Subtotal-nephrectomy or sham operation was performed in 8-week-old C57BL/6J mice. They were divided into two groups with or without 8% (w/w) of AST-120 in standard diet for 20 weeks. Sham, Sham + AST-120, CKD and CKD + AST-120 (n = 12, each group) were studied. We also conducted a C2C12 cell culture study to determine the direct effects of IS on oxidative stress. RESULTS: Plasma IS levels were significantly increased in CKD compared with Sham (1.05 ± 0.11 versus 0.21 ± 0.03 mg/dL, P <0.05), which was significantly ameliorated in CKD + AST-120 (0.41 ± 0.06 mg/dL). The running distance to exhaustion determined by treadmill tests was significantly reduced in CKD compared with Sham (267 ± 17 versus 427 ± 36 m, P <0.05), and this reduction was also significantly ameliorated in CKD + AST-120 (407 ± 38 m) without altering skeletal muscle weight. Citrate synthase activity and mitochondrial biogenesis gene were downregulated, and superoxide production was significantly increased in the skeletal muscle from CKD, and these changes were normalized in CKD + AST-120. Incubation of C2C12 cells with IS significantly increased NAD(P)H oxidase activity. CONCLUSIONS: The administration of AST-120 improved exercise capacity and mitochondrial biogenesis of skeletal muscle via reducing oxidative stress. AST-120 may be a novel therapeutic agent against exercise intolerance in CKD.

Report of the American Heart Association (AHA) Scientific Sessions 2013, Dallas.

The American Heart Association (AHA) Scientific Sessions were held in Dallas on November 16-20, 2013. The meeting is one of the most leading conferences of cardiology in the world, with over 18,000 professional attendees from more than 105 countries. There were 315 invited sessions and 443 abstract sessions, comprising more than 5,000 presentations. The sessions were expanded to 26 program tracks, which included and integrated basic, translational, clinical, and population science. In the series of late-breaking sessions, updates of results from 20 clinical trials were disclosed. Japanese scientists submitted the second most abstracts to the Scientific Sessions in 2013. We appreciate the significant contribution to the sessions by Japanese cardiologists as well as the Japanese Circulation Society.

Hyponatremia is an independent predictor of adverse clinical outcomes in hospitalized patients due to worsening heart failure.

BACKGROUND AND PURPOSE: Hyponatremia is common and is associated with poor in-hospital outcomes in patients hospitalized with heart failure (HF). However, it is unknown whether hyponatremia is associated with long-term adverse outcomes. The purpose of this study was to clarify the characteristics, clinical status on admission, and management during hospitalization according to the serum sodium concentration on admission, and determine whether hyponatremia was associated with in-hospital as well as long-term outcomes in 1677 patients hospitalized with worsening HF on index hospitalization registered in the database of the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD). METHODS AND SUBJECTS: We studied the characteristics and in-hospital treatment in 1659 patients hospitalized with worsening HF by using the JCARE-CARD database. Patients were divided into 2 groups according to serum sodium concentration on admission <135mEq/mL (n=176; 10.6%) or ≥135mEq/mL (n=1483; 89.4%). RESULTS: The mean age was 70.7 years and 59.2% were male. Etiology was ischemic in 33.9% and mean left ventricular ejection fraction was 42.4%. After adjustment for covariates, hyponatremia was independently associated with in-hospital death [adjusted odds ratio (OR) 2.453, 95% confidence interval (CI) 1.265-4.755, p=0.008]. It was significantly associated also with adverse long-term (mean 2.1±0.8 years) outcomes including all-cause death (OR 1.952, 95% CI 1.433-2.657), cardiac death (OR 2.053, 95% CI 1.413-2.983), and rehospitalization due to worsening HF (OR 1.488, 95% CI 1.134-1.953). CONCLUSIONS: Hyponatremia was independently associated with not only in-hospital but also long-term adverse outcomes in patients hospitalized with worsening HF.

Activation of invariant natural killer T cells by α-galactosylceramide ameliorates myocardial ischemia/reperfusion injury in mice.

Invariant natural killer T (iNKT) cells orchestrate tissue inflammation via regulating various cytokine productions. However the role of iNKT cells has not been determined in myocardial ischemia/reperfusion (I/R) injury. The purpose of this study was to examine whether the activation of iNKT cells by α-galactosylceramide (α-GC), which specifically activates iNKT cells, could affect myocardial I/R injury. I/R or sham operation was performed in male C57BL/6J mice. I/R mice received the injection of either αGC (I/R+αGC, n=48) or vehicle (I/R+vehicle, n=49) 30 min before reperfusion. After 24h, infarct size/area at risk was smaller in I/R+αGC than in I/R+vehicle (37.8 ± 2.7% vs. 47.1 ± 2.5%, P<0.05), with no significant changes in area at risk. The numbers of infiltrating myeloperoxidase- and CD3-positive cells were lower in I/R+αGC. Apoptosis evaluated by TUNEL staining and caspase-3 protein was also attenuated in I/R+αGC. Myocardial gene expression of tumor necrosis factor-α and interleukin (IL)-1ß in I/R+αGC was lower to 46% and 80% of that in I/R+vehicle, respectively, whereas IL-10, IL-4, and interferon (IFN)-γ were higher in I/R+αGC than I/R+vehicle by 2.0, 4.1, and 9.6 folds, respectively. The administration of anti-IL-10 receptor antibody into I/R+αGC abolished the protective effects of αGC on I/R injury (infarct size/area at risk: 53.1 ± 5.2% vs. 37.4 ± 3.5%, P<0.05). In contrast, anti-IL-4 and anti-IFN-γ antibodies did not exert such effects. In conclusion, activated iNKT cells by αGC play a protective role against myocardial I/R injury through the enhanced expression of IL-10. Therapies designed to activate iNKT cells might be beneficial to protect the heart from I/R injury.

Natural killer T cells are required for lipopolysaccharide-mediated enhancement of atherosclerosis in apolipoprotein E-deficient mice.

Lipopolysaccharide (LPS) has been shown to accelerate atherosclerosis and to increase the prevalence of IL-4-producing natural killer T (NKT) cells in various tissues. However, the role of NKT cells in the development of LPS-induced atherosclerotic lesions has not been fully tested in NKT cell-deficient mice. Here, we examined the lesion development in apolipoprotein E knockout (apoE-KO) mice and apoE-KO mice on an NKT cell-deficient, CD1d knockout (CD1d-KO) background (apoE-CD1d double knockout; DKO). LPS (0.5 µg/g body weight/wk) or phosphate-buffered saline (PBS) was intraperitoneally administered to apoE-KO and DKO mice (8-wk old) for 5 wk and atherosclerotic lesion areas were quantified thereafter. Consistent with prior reports, NKT cell-deficient DKO mice showed milder atherosclerotic lesions than apoE-KO mice. Notably, LPS administration significantly increased the lesion size in apoE-KO, but not in DKO mice, compared to PBS controls. Our findings suggest that LPS, and possibly LPS-producing bacteria, aggravate the development of atherosclerosis primarily through NKT cell activation and subsequent collaboration with NK cells.

Activation of natural killer T cells ameliorates postinfarct cardiac remodeling and failure in mice.

RATIONALE: Chronic inflammation in the myocardium is involved in the development of left ventricular (LV) remodeling and failure after myocardial infarction (MI). Invariant natural killer T (iNKT) cells have been shown to produce inflammatory cytokines and orchestrate tissue inflammation. However, no previous studies have determined the pathophysiological role of iNKT cells in post-MI LV remodeling. OBJECTIVE: The purpose of this study was to examine whether the activation of iNKT cells might affect the development of LV remodeling and failure. METHODS AND RESULTS: After creation of MI, mice received the injection of either α-galactosylceramide (αGC; n=27), the activator of iNKT cells, or phosphate-buffered saline (n=31) 1 and 4 days after surgery, and were followed during 28 days. Survival rate was significantly higher in MI+αGC than MI+PBS (59% versus 32%, P<0.05). LV cavity dilatation and dysfunction were significantly attenuated in MI+αGC, despite comparable infarct size, accompanied by a decrease in myocyte hypertrophy, interstitial fibrosis, and apoptosis. The infiltration of iNKT cells were increased during early phase in noninfarcted LV from MI and αGC further enhanced them. It also enhanced LV interleukin (IL)-10 gene expression at 7 days, which persisted until 28 days. AntienIL-10 receptor antibody abrogated these protective effects of αGC on MI remodeling. The administration of αGC into iNKT cell-deficient Jα18(-/-) mice had no such effects, suggesting that αGC was a specific activator of iNKT cells. CONCLUSIONS: iNKT cells play a protective role against post-MI LV remodeling and failure through the enhanced expression of cardioprotective cytokines such as IL-10.

Type II NKT cells stimulate diet-induced obesity by mediating adipose tissue inflammation, steatohepatitis and insulin resistance.

The progression of obesity is accompanied by a chronic inflammatory process that involves both innate and acquired immunity. Natural killer T (NKT) cells recognize lipid antigens and are also distributed in adipose tissue. To examine the involvement of NKT cells in the development of obesity, C57BL/6 mice (wild type; WT), and two NKT-cell-deficient strains, Jα18(-/-) mice that lack the type I subset and CD1d(-/-) mice that lack both the type I and II subsets, were fed a high fat diet (HFD). CD1d(-/-) mice gained the least body weight with the least weight in perigonadal and brown adipose tissue as well as in the liver, compared to WT or Jα18(-/-) mice fed an HFD. Histologically, CD1d(-/-) mice had significantly smaller adipocytes and developed significantly milder hepatosteatosis than WT or Jα18(-/-) mice. The number of NK1.1(+)TCRß(+) cells in adipose tissue increased when WT mice were fed an HFD and were mostly invariant Vα14Jα18-negative. CD11b(+) macrophages (Mφ) were another major subset of cells in adipose tissue infiltrates, and they were divided into F4/80(high) and F4/80(low) cells. The F4/80(low)-Mφ subset in adipose tissue was increased in CD1d(-/-) mice, and this population likely played an anti-inflammatory role. Glucose intolerance and insulin resistance in CD1d(-/-) mice were not aggravated as in WT or Jα18(-/-) mice fed an HFD, likely due to a lower grade of inflammation and adiposity. Collectively, our findings provide evidence that type II NKT cells initiate inflammation in the liver and adipose tissue and exacerbate the course of obesity that leads to insulin resistance.

Decreased glomerular filtration rate is a significant and independent risk for in-hospital mortality in Japanese patients with acute myocardial infarction: report from the Hokkaido acute myocardial infarction registry.

Renal dysfunction is a significant risk factor in the prognosis of patients with cardiovascular diseases. We sought to determine the relationship between estimated glomerular filtration rate (eGFR) values and in-hospital mortality in Japanese acute myocardial infarction (AMI) patients. A total of 2266 consecutive AMI patients admitted to 22 hospitals in Hokkaido were registered. The eGFR values were determined using the following equation: eGFR=194 × (serum creatinine)(-1.094) × (age)(-0.287) ( × 0.739 if female). Patients were classified into four groups according to their eGFR values: ≥60 (n=1304), 30-59 (n=810), 15-29 (n=87) and <15 ml min(-1) per 1.73 m(2) (n=65). A total of 110 patients (4.9%) died during hospitalization. The in-hospital mortality rate was significantly higher in patients with reduced eGFR values at 2.3, 5.4, 24.1 and 23.1% for eGFR values of ≥60, 30-59, 15-29, and <15 ml min(-1) per 1.73 m(2), respectively. The odds ratios for in-hospital all cause death were 8.26 (95% confidence interval (CI): 2.22-30.77) for eGFR<15 ml min(-1) per 1.73 m(2) and 3.42 (95% CI: 1.01-11.61) for eGFR 15-29 ml min(-1) per 1.73 m(2) compared with eGFR ≥60 ml min(-1) per 1.73 m(2). Similarly, the odds ratios for in-hospital cardiac death were 8.43 (95% CI: 1.82-39.05) for eGFR<15 ml min(-1) per 1.73 m(2) and 5.47 (95% CI: 1.51-19.80) for eGFR 15-29 ml min(-1) per 1.73 m(2). In conclusion, the eGFR of <30 ml min(-1) per 1.73 m(2) was a significant and independent risk for in-hospital mortality in abroad cohort of Japanese patients with AMI.

Identification and further differentiation of subendocardial and transmural myocardial infarction by fast strain-encoded (SENC) magnetic resonance imaging at 3.0 Tesla.

OBJECTIVES: To investigate whether subendocardial and transmural myocardial infarction can be identified and differentiated using the peak circumferential and longitudinal strains measured by fast strain-encoded (SENC). METHODS: Nineteen patients with ischemic heart diseases underwent imaging with fast SENC and late gadolinium enhancement (LGE) MRI at 3 T. Fast SENC measurements were performed in three short-axis slices (basal, mid-ventricular and apical levels) and one long-axis view (four-chamber) to assess peak longitudinal and circumferential systolic strains. RESULTS: All patients showed myocardial infarction with an average of 7 positive LGE segments. A total of 304 segments for longitudinal strains (LS) and 114 segments for circumferential strains (CS) could be analysed. Positive LGE segments showed lower peak CS and LS compared with the no LGE segments (P < 0.0001 for both). Segments with subendocardial infarction showed reduced CS and LS compared with the no LGE segments (P < 0.0001 for both). There was a significant difference in CS between subendocardial and transmural infarct segments (P = 0.03), but no significant difference in LS between them (P = 0.64). CONCLUSIONS: Fast SENC can identify old myocardial infarction and differentiate subendocardial from transmural infarction.