Paget-Schroetter Syndrome in a Baseball Pitcher.

Paget-Schroetter syndrome (PSS) is thrombosis of the deep veins draining the upper extremity due to anatomic abnormalities of the thoracic outlet that cause subclavian compression and subsequent thrombosis, leading to thrombus formation in the subclavian vein. Vigorous arm activity in sports is a known risk factor. Here, we report a case of Paget-Schroetter syndrome in a 31-year-old male non-professional baseball pitcher.

Low Serum Levels of Eicosapentaenoic Acid and Docosahexaenoic Acid are Risk Factors for Cardiogenic Syncope in Patients with Brugada Syndrome.

The n-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have antiarrhythmic effects, possibly via modulation of the cardiac ion channels. Nevertheless, it is unknown whether low serum levels of n-3 PUFAs are risk factors for ventricular fibrillation in patients with Brugada syndrome (BrS). We retrospectively reviewed data from 62 men with BrS and evaluated their serum levels of EPA and DHA, and the risk factors for sudden cardiac death, including a history of cardiogenic syncope. Nineteen patients had a history of cardiogenic syncope, and their EPA and DHA levels were significantly lower than those of the patients without syncope. Multivariate logistic regression analysis revealed that low EPA and DHA levels were associated with the incidence of syncope. The receiver-operator characteristic curve showed the area under the curves of EPA and DHA for history of syncope were 0.84 and 0.72, respectively. In conclusion, low levels of EPA and DHA are risk factors for cardiogenic syncope in patients with BrS, which suggests that n-3 PUFAs play important roles in preventing ventricular fibrillation in BrS.

Improved Exercise Capacity After Cardiac Rehabilitation Is Associated with Reduced Visceral Fat in Patients with Chronic Heart Failure.

Participation in a comprehensive cardiac rehabilitation (CR) program has been shown to reduce mortality and improve exercise capacity and symptoms in patients with chronic heart failure (CHF). Reduced exercise capacity leads to a concomitant reduction of skeletal muscle mass and accumulation of body fat. However, it is currently unknown whether CR reduces visceral adipose tissue (VAT) and/or subcutaneous abdominal adipose tissue (SAT) in patients with CHF. In addition, the body composition associated with improved exercise capacity after CR in patients with CHF has not been previously studied. Nineteen CHF patients who were categorized as NYHA functional class II or III and had received optimal medical treatment including a CR program for 5 months were enrolled in this study. The CR program significantly increased peak VO2 and reduced B-type natriuretic peptide. In addition, fat and body composition analysis showed reductions in the visceral fat tissue (VAT) area, subcutaneous abdominal adipose tissue (SAT) area, body weight, and total fat weight after CR. There were no changes in total water weight and total muscle weight. Single regression analysis revealed that the amelioration of reduced exercise capacity seen after CR is associated with reduced VAT area but not with SAT area or body weight. In conclusion, CR reduces VAT and improves exercise capacity in patients with CHF. This suggests that reducing VAT is important for CR to be most effective in the treatment of CHF.

Identification of activators of ERK5 transcriptional activity by high-throughput screening and the role of endothelial ERK5 in vasoprotective effects induced by statins and antimalarial agents.

Because ERK5 inhibits endothelial inflammation and dysfunction, activating ERK5 might be a novel approach to protecting vascular endothelial cells (ECs) against various pathological conditions of the blood vessel. We have identified small molecules that protect ECs via ERK5 activation and determined their contribution to preventing cardiac allograft rejection. Using high-throughput screening, we identified certain statins and antimalarial agents including chloroquine, hydroxychloroquine, and quinacrine as strong ERK5 activators. Pitavastatin enhanced ERK5 transcriptional activity and Kruppel-like factor-2 expression in cultured human and bovine ECs, but these effects were abolished by the depletion of ERK5. Chloroquine and hydroxychloroquine upregulated ERK5 kinase activity and inhibited VCAM-1 expression in an ERK5-dependent but MAPK/ERK kinase 5- and Kruppel-like factor 2/4-independent manner. Leukocyte rolling and vascular reactivity were used to evaluate endothelial function in vivo, and we found that EC-specific ERK5 knockout (ERK5-EKO) mice exhibited increased leukocyte rolling and impaired vascular reactivity, which could not be corrected by pitavastatin. The role of endothelial ERK5 in acute cardiac allograft rejection was also examined by heterotopic grafting of the heart obtained from either wild-type or ERK5-EKO mice into allomismatched recipient mice. A robust increase in both inflammatory gene expression and CD45-positive cell infiltration into the graft was observed. These tissue rejection responses were inhibited by pitavastatin in wild-type but not ERK5-EKO hearts. Our study has identified statins and antimalarial drugs as strong ERK5 activators and shown that ERK5 activation is preventive of endothelial inflammation and dysfunction and acute allograft rejection.

Response Prediction and Influence of Tolvaptan in Chronic Heart Failure Patients Considering the Interaction of the Renin-Angiotensin-Aldosterone System and Arginine Vasopressin.

The renin-angiotensin-aldosterone system (RAAS) and arginine vasopressin (AVP) regulate body fluids. Although conventional diuretics have been used for treating heart failure, they activate RAAS and exacerbate renal function. Tolvaptan, a newly developed vasopressin-2 receptor antagonist, elicits aquaresis and improves volume overload in heart failure patients, however, the predictors of tolvaptan effectiveness and the influence on the RAAS and renal function according to tolvaptan therapy are not established. We evaluated 26 chronic heart failure patients receiving therapy with 15 mg/day tolvaptan and examined their laboratory and urinary data before and after tolvaptan therapy. A response to tolvaptan was defined as a body weight decrease by more than 2 kg in a week and a urine volume increase by 500 mL/ day compared with that before tolvaptan administration. Body weight, urine volume, and brain natriuretic peptide levels significantly improved (P < 0.05), without any worsening of renal function represented by serum creatinine, sodium, and potassium. Moreover, no significant changes were observed in the plasma renin activity and plasma aldosterone concentration (PAC). In the responder group, urine osmolality before tolvaptan administration was significantly higher (P < 0.05) but declined significantly after tolvaptan administration (P < 0.05). The AVP/PAC ratio before administration was positively correlated with the efficacy of tolvaptan. Tolvaptan treatment could prevent RAAS activation in chronic heart failure patients. Moreover, monitoring the AVP/PAC ratio may be useful in predicting the tolvaptan response.

ERK5 activation in macrophages promotes efferocytosis and inhibits atherosclerosis.

BACKGROUND: Efferocytosis is a process by which dead and dying cells are removed by phagocytic cells. Efferocytosis by macrophages is thought to curb the progression of atherosclerosis, but the mechanistic insight of this process is lacking. METHODS AND RESULTS: When macrophages were fed apoptotic cells or treated with pitavastatin in vitro, efferocytosis-related signaling and phagocytic capacity were upregulated in an ERK5 activity-dependent manner. Macrophages isolated from macrophage-specific ERK5-null mice exhibited reduced efferocytosis and levels of gene and protein expression of efferocytosis-related molecules. When these mice were crossed with low-density lipoprotein receptor(-/-) mice and fed a high-cholesterol diet, atherosclerotic plaque formation was accelerated, and the plaques had more advanced and vulnerable morphology. CONCLUSIONS: Our results demonstrate that ERK5, which is robustly activated by statins, is a hub molecule that upregulates macrophage efferocytosis, thereby suppressing atherosclerotic plaque formation. Molecules that upregulate ERK5 and its signaling in macrophages may be good drug targets for suppressing cardiovascular diseases.

Reduced ratio of eicosapentaenoic acid and docosahexaenoic acid to arachidonic acid is associated with early onset of acute coronary syndrome.

BACKGROUND: The hospitalization rate for acute coronary syndrome (ACS) for people aged ≤50 has remained stable over the past decade. Increased serum levels of n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a decreased incidence of cardiovascular events and mortality in older patients; however, it is currently unknown whether reduced serum levels of n-3 PUFAs is also a risk factor for ACS in patients aged ≤50 years. METHODS AND RESULTS: We retrospectively reviewed 102 (male/ female 73/29) Japanese ACS patients whose serum levels of EPA/arachidonic acid (AA) and DHA/AA were evaluated on admission. The EPA/AA ratio was the lowest in patients aged ≤50 compared to patients aged 51-74 and ≥75. Pearson correlation analysis showed that early ACS onset was associated with low EPA/AA and DHA/AA ratios, and multiple regression analysis determined that decreased ratios of EPA/AA and DHA/AA, and male sex, current smoker status, increased body mass index and triglyceride levels, independently correlated with early ACS onset. Conversely, low-density and high-density lipoproteins, glycated hemoglobin, and hypertension did not correlate with early ACS onset. Subgroup analyses of male patients revealed that decreased ratios of EPA/AA and DHA/AA independently correlated with early ACS onset. CONCLUSION: Decreased EPA/AA and DHA/AA ratios may be risk factors for early onset of ACS, suggesting that reduced EPA/AA and DHA/AA may represent targets for preventing ACS in Japanese young people.

Impact of supervised cardiac rehabilitation on urinary albumin excretion in patients with cardiovascular disease.

Urinary albumin excretion is a predictor of cardiovascular death. Cardiac rehabilitation (CR) with exercise training (ET) has been shown to improve exercise capacity and prognosis in patients with cardiovascular disease (CVD). However, it remains unclear whether CR reduces urinary albumin excretion in CVD patients. We performed a retrospective, observational study using data obtained from 98 male CVD patients without macroalbuminuria and estimated glomerular filtration rate (eGFR) < 30 mL/minute/1.73 m(2) who participated in CR with ET during hospitalization. Twenty-three patients continued supervised ET for 6 months (supervised group) and 75 patients quit supervised ET (non-supervised group). The supervised ET program consisted of 60 minutes of supervised sessions 1-3 times a week and 30-60 minutes of home exercise at least twice a week. Urinary albumin/creatinine ratio (ACR) was significantly decreased in the supervised group at 6 months after enrollment (43 ± 71 mg/g to 17 ± 20 mg/g creatinine, P < 0.05) but not in the non-supervised group. eGFR was unchanged in the supervised group but was significantly decreased in the non-supervised group (72 ± 18 mL/minute/1.73 m(2) to 67 ± 17 mL/minute/1.73 m(2), P < 0.001). The results of multiple regression analysis showed that only supervised ET was an independent contributor to ΔACR. CR with supervised ET decreased urinary albumin excretion without deterioration of renal function. These findings suggest that continuation of a supervised ET program is associated with reduction in the development of CVD and reduction in cardiovascular morbidity and mortality in CVD patients.

Androgen receptor promotes sex-independent angiogenesis in response to ischemia and is required for activation of vascular endothelial growth factor receptor signaling.

BACKGROUND: Hypoandrogenemia is associated with an increased risk of ischemic diseases. Because actions of androgens are exerted through androgen receptor (AR) activation, we studied hind-limb ischemia in AR knockout mice to elucidate the role of AR in response to ischemia. METHODS AND RESULTS: Both male and female AR knockout mice exhibited impaired blood flow recovery, more cellular apoptosis, and a higher incidence of autoamputation after ischemia. In ex vivo and in vivo angiogenesis studies, AR-deficient vascular endothelial cells showed reduced angiogenic capability. In ischemic limbs of AR knockout mice, reductions in the phosphorylation of the Akt protein kinase and endothelial nitric oxide synthase were observed despite a robust increase in hypoxia-inducible factor 1α and vascular endothelial cell growth factor (VEGF) gene expression. In in vitro studies, siRNA-mediated ablation of AR in vascular endothelial cells blunted VEGF-stimulated phosphorylation of Akt and endothelial nitric oxide synthase. Immunoprecipitation experiments documented an association between AR and kinase insert domain protein receptor that promoted the recruitment of downstream signaling components. CONCLUSIONS: These results document a physiological role of AR in sex-independent angiogenic potency and provide evidence of novel cross-talk between the androgen/AR signaling and VEGF/kinase insert domain protein receptor signaling pathways.

Cardiac rehabilitation reduces serum levels of oxidized low-density lipoprotein.

BACKGROUND: Oxidized low-density lipoprotein (oxLDL) levels have been found to play an important role in the progression of atherosclerosis. However, methods for effectively reducing oxLDL levels have not been established. Comprehensive cardiac rehabilitation (CR) with exercise training prevents the progression of atherosclerosis, and might reduce oxLDL levels. METHODS AND RESULTS: We measured the serum levels of malondialdehyde-modified LDL (MDA-LDL), a marker of oxLDL, in 136 patients who were enrolled in a 6-month CR program. Peak oxygen consumption (V̇O2) and MDA-LDL levels were analyzed, before and 6 months after enrolment. In total, 67 patients completed the CR program (CR group) and 69 patients failed to complete the program (non-CR group). Peak V̇O2increased significantly in the CR group (P<0.01). The levels of MDA-LDL decreased significantly in the CR group (P<0.01) but not in the non-CR group. ∆V̇O2(peak V̇O2after CR-peak V̇O2before CR) was negatively associated with ∆MDA-LDL (MDA-LDL after CR-MDA-LDL before CR) (R(2)=0.11, P=0.01). Multiple regression analysis showed that continuing CR was an independent determining factor for lowering MDA-LDL levels. CONCLUSIONS: CR decreases oxLDL levels in patients with cardiovascular diseases. Moreover, CR may prevent cardiovascular events through an antioxidative effect.

Serum concentration of eicosapentaenoic acid is associated with cognitive function in patients with coronary artery disease.

BACKGROUND: Recent studies have shown that intake of n-3 polyunsaturated fatty acids (PUFAs) is associated with reduced risk of cognitive impairment and coronary artery disease (CAD); however, it is currently unknown whether reduced serum n-3 PUFA is associated with cognitive impairment in patients with CAD. METHODS: We retrospectively evaluated cognitive function with the mini-mental state examination (MMSE), serum levels of PUFAs (including eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA], dihomogammalinolenic acid [DGLA], and arachidonic acid [AA]), cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, and history of current/previous smoking), and parameters of cardiac function (left ventricular ejection fraction and brain natriuretic peptide levels) in 146 Japanese CAD patients. The associations between the MMSE scores and the other parameters were evaluated. RESULTS: Pearson correlation analysis showed that EPA (R = 0.25, P <0.01), EPA/AA ratio (R = 0.22, P = 0.01), and left ventricular ejection fraction (R = 0.15, P = 0.04) were positively associated with MMSE score, and that age (R = -0.20, P <0.01) and brain natriuretic peptide levels (R = -0.28, P <0.01) were inversely associated with MMSE score. Multiple regression analysis showed that age (P <0.05) was negatively associated with MMSE score, while EPA (P <0.01) and EPA/AA ratio (P <0.05) were positively associated with MMSE score; however, sex; body mass index; left ventricular ejection fraction; levels of DHA, AA, and DGLA; DHA/AA ratio; brain natriuretic peptide; and presence of hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, and history of current/previous smoking were statistically excluded. CONCLUSIONS: Serum EPA concentration is associated with cognitive function in patients with CAD, suggesting that a low serum EPA level is a risk factor for cognitive impairment independent of cardiac function, including left ventricular ejection fraction. This correlation potentially lends further support to a role of dietary n-3 PUFAs in preventing the cognitive decline in CAD patients.

Congenital long QT syndrome with compound mutations in the KCNH2 gene.

Congenital long QT syndrome is a genetic disorder encompassing a family of mutations that can lead to aberrant ventricular electrical activity. We report on two brothers with long QT syndrome caused by compound mutations in the KCNH2 gene inherited from parents who had no prolonged QT interval on electrocardiography. The proband had syncope, and his elder brother suffered from ventricular fibrillation. Genetic testing revealed that both brothers had multiple mutations in the KCNH2 gene, including a missense mutation of C1474T (exon 6) as well as a frameshift/nonsense mutation, resulting from the insertion of 25 nucleotides, which caused an altered amino acid sequence beginning at codon 302 and a premature termination codon (i.e., TAG) at codon 339 (exon 4). Family genetic screening found that their father had the same frameshift mutation, and their mother and sister had the same missense mutation, in the KCNH2 gene. However, these other family members were asymptomatic, with normal QT intervals on electrocardiography. These results suggest that compound mutations in the KCNH2 gene inherited independently from the parents made the phenotypes of their sons more severe.

High serum parathyroid hormone and calcium are risk factors for hypertension in Japanese patients.

Excess parathyroid hormone (PTH), known as primary hyperparathyroidism (pHPT), results in hypercalcemia and bone loss. Recent studies have shown that PTH is associated with the occurrence of hypertension in Western countries; however, controversy remains regarding high serum levels of PTH and calcium as risk factors for hypertension in Japanese patients. We retrospectively enrolled 114 consecutive Japanese patients who visited our hospital for examination and treatment of hypercalcemia and/or hypertension with serum calcium levels ≥ 9.8 mg/dL. To estimate the prevalence of hypertension, the patients were categorized according to calcium levels into hypercalcemic (10.2-13.4 mg/dL) and normocalcemic (9.8-10.1 mg/dL) groups, which were further categorized into high PTH (50-440 pg/mL) and low PTH (8-49 pg/mL) groups. The prevalence of hypertension was higher in patients with hypercalcemia than in patients with normocalcemia in both the high and low PTH groups. The prevalence of hypertension was higher in patients with high serum PTH levels than in patients with low serum PTH levels in both the hypercalcemic and normocalcemic groups. Logistic multiple regression analysis determined that serum calcium (P < 0.05) and PTH (P < 0.01) levels were positive contributors to hypertension. In conclusion, high serum levels of PTH and calcium are risk factors for hypertension in Japanese patients.

Heparin cofactor II, a serine protease inhibitor, promotes angiogenesis via activation of the AMP-activated protein kinase-endothelial nitric-oxide synthase signaling pathway.

We previously clarified that heparin cofactor II (HCII), a serine proteinase inhibitor, exerts various protective actions on cardiovascular diseases in both experimental and clinical studies. In the present study, we aimed to clarify whether HCII participates in the regulation of angiogenesis. Male heterozygous HCII-deficient (HCII(+/-)) mice and male littermate wild-type (HCII(+/+)) mice at the age of 12-16 weeks were subjected to unilateral hindlimb ligation surgery. Laser speckle blood flow analysis showed that blood flow recovery in response to hindlimb ischemia was delayed in HCII(+/-) mice compared with that in HCII(+/+) mice. Capillary number, arteriole number, and endothelial nitric-oxide synthase (eNOS), AMP-activated protein kinase (AMPK), and liver kinase B1 (LKB1) phosphorylation in ischemic muscles were decreased in HCII(+/-) mice. Human purified HCII (h-HCII) administration almost restored blood flow recovery, capillary density, and arteriole number as well as phosphorylation levels of eNOS, AMPK, and LKB1 in ischemic muscles of HCII(+/-) mice. Although treatment with h-HCII increased phosphorylation levels of eNOS, AMPK, and LKB1 in human aortic endothelial cells (HAECs), the h-HCII-induced eNOS phosphorylation was abolished by compound C, an AMPK inhibitor, and by AMPK siRNA. In a similar fashion, tube formation, proliferation, and migration of HAECs were also promoted by h-HCII treatment and were abrogated by pretreatment with compound C. HCII potentiates the activation of vascular endothelial cells and the promotion of angiogenesis in response to hindlimb ischemia via an AMPK-eNOS signaling pathway. These findings suggest that HCII is a novel therapeutic target for treatment of patients with peripheral circulation insufficiency.

Ghrelin protects the heart against ischemia-induced arrhythmias by preserving connexin-43 protein.

Vagal nerve stimulation has been postulated to confer an antifibrillatory effect. We studied whether ghrelin administration would exert an antiarrhythmic effect via modulation of autonomic nerve activity in rats after acute myocardial ischemia (MI). Male Sprague-Dawley rats were exposed to 30 min of ischemia following ligation of the left coronary artery. Animals were then randomized to receive either ghrelin (n = 26) or saline (n = 26) during the period of coronary ligation. Power spectral analysis of heart-rate variability revealed that the administration of ghrelin increased the high-frequency (HF) power and decreased the low-frequency (LF)/HF ratio. Ventricular tachyarrhythmias were less frequent in rats after MI who received ghrelin in comparison with rats that received saline. Immunoblotting and immunohistochemistry revealed that rats given saline alone during MI exhibited a marked reduction in phosphorylated connexin-43 within the left ventricle, whereas those that received ghrelin displayed only minor reductions in comparison with sham-operated rats. These effects of ghrelin were diminished by the coadministration of atropine or the blockade of vagal afferents. These data demonstrate that the beneficial effect of ghrelin might be mediated by modulation of cardiac autonomic nerve activity.

Pharmacology of Aldosterone and the Effects of Mineralocorticoid Receptor Blockade on Cardiovascular Systems.

UNLABELLED: It is well-known that aldosterone plays an important role in reabsorption of sodium and fluid, and in potassium excretion in kidneys via epithelial mineralocorticoid receptor (MR) activation. Recent studies have shown that aldosterone causes cardiovascular remodeling not only in a blood pressure-dependent manner, but also in a blood pressure-independent manner by decreasing nitric oxide bioavailability and modulating oxidative stress, leading to vascular inflammation. In addition, MR blockade does provide beneficial effects associated with cardiovascular protection, resulting in a reduction of cardiovascular morbidity and mortality. A growing body of evidence suggests that MR blockade is a promising therapeutic target to help prevent cardiovascular events. KEY WORDS: Aldosterone; Mineralocorticoid receptor; Nitrix oxide; Renin-angiotensin-aldosterone system.

Medical English Education in Japan†:†Developing a Curriculum to Motivate Students by Providing Visualization Opportunities Using Near-peer Teaching.

Despite advancements in the pedagogy of medical education in various fields, Japan has no standardized medical English education. The U.S. Medical Licensing Examination (USMLE) Study Group of Tokushima is an extracurricular activity in which medical students and recent graduates meet every 1-2 months. The aim is to stimulate students' curiosity ; cultivate their initiative, self-efficacy, and English learning goals ; and motivate them to be self-regulated learners. Accordingly, we conducted near-peer teaching style lectures that focused on sharing medical English-related experiences, so students could have regular opportunities to visualize the benefits of learning medical English. Following the activities, we observed increased motivation and self-study among students, resulting in a high USMLE passing rate. Furthermore, five members started their training at American hospitals and pursued careers in English-speaking environments. Thus, near-peer teaching style leads to shared medical English-related experiences that help students to visualize English-related opportunities. This education style taught by similar generations aids in setting a specific goal by providing access to role models, cultivating their initiative and self-efficacy, motivating them to learn English, and producing positive outcomes.Modifying the curriculum to actively create opportunities for students to visualize themselves in an international environment can motivate them to continue learning English. J. Med. Invest. 69 : 332-334, August, 2022.

Role of hypoxia-inducible factor 1alpha in T cells as a negative regulator in development of vascular remodeling.

BACKGROUND AND PURPOSE: Recent studies have shown that the cellular immune response in the development of vascular remodeling modulates the resulting pathological alterations. We show that hypoxia-inducible factor 1 (Hif-1) (specifically expressed in T cells) is involved in the immune response to vascular remodeling that accompanies arteriosclerosis. METHODS AND RESULTS: To study the role of T cells in the development of vascular remodeling, femoral arterial injury induced by an external vascular polyethylene cuff was examined in mice lacking Hif-1 (specifically in T cells). We found that cuff placement caused prominent neointimal hyperplasia of the femoral artery in Hif-1- (T-cell)-deficient mice compared with that in control mice and that infiltration of inflammatory cells at the adventitia was markedly increased in the mutant mice. Studies to clarify the mechanism of augmented vascular remodeling in the mutant mice showed enhanced production of cytokines by activated T cells and augmented antibody production in response to a T-dependent antigen in the mutant mice. CONCLUSIONS: The results of this study revealed that Hif-1alpha in T cells plays a crucial role in vascular inflammation and remodeling in response to cuff injury as a negative regulator of T cell-mediated immune response. Potential new therapeutic strategies that target Hif-1alpha are described.

Validation of longitudinal peak systolic strain by speckle tracking echocardiography with visual assessment and myocardial perfusion SPECT in patients with regional asynergy.

BACKGROUND: Automated function imaging (AFI) is a recently developed method of calculating the longitudinal peak systolic strains (LS) of the regional left ventricular (LV) wall using speckle tracking echocardiography and displaying them on a single bull's-eye map. The feasibility of AFI in patients with regional LV wall motion abnormalities caused by myocardial infarction (MI) was evaluated by comparison with visual assessment and myocardial perfusion single-photon emission computed tomography (SPECT). METHODS AND RESULTS: Segmental LS was measured by AFI in 60 patients with MI (67 ± 11 years) and 58 controls (71 ± 9 years). Wall thickening (WT) was measured by SPECT in 20 patients with MI. There was a strong positive linear relationship between the wall motion score index by expert visual assessment and global LS. The receiver-operating characteristic analysis revealed the best cutoff value of 11% < LS to identify hypokinetic segments. The overall accuracy of wall motion scoring by LS in the 2,006 segments was 96.8% (κ = 0.90) compared with visual assessment. The correlation coefficient between LS and WT was R² = 0.65 in the 340 segments. CONCLUSIONS: Assessment of LV regional asynergy by AFI showed good agreement with visual and SPECT assessments. AFI is clinically useful for quantitative assessment of LV regional wall motion abnormalities.

Enhanced inflammation in epicardial fat in patients with coronary artery disease.

It has been hypothesized that epicardial fat, a local visceral fat depot with close proximity to coronary arteries, may serve as a source of inflammatory cytokines and cells in coronary atherosclerotic lesions. Here, we characterized infiltration of inflammatory cells and expression of adipocytokines in epicardial adipose tissue in patients with and without coronary artery disease (CAD). Pare samples were obtained from epicardial and subcutaneous adipose tissue during elective cardiac surgery (CAD, n = 8; non-CAD, n = 9). Inflammatory cell infiltration was investigated by immunohistochemical staining using antibodies against CD3, CD4, CD8 and CD68. Expression of adipocytokines was evaluated by real-time quantitative reverse transcription-polymerase chain reaction. Infiltration of macrophages and CD8-positive T cells in the epicardial adipose tissue in the CAD group was greater than that in the non-CAD group. In contrast, there was no significant difference between the two groups in the number of inflammatory cells in subcutaneous adipose tissue. No statistical difference could be found between the CAD group and the non-CAD group in the expression levels of adiponectin and inflammatory cytokines in epicardial adipose tissue. Our findings suggest that inflammatory cell infiltration is enhanced in epicardial adipose tissue, but not in subcutaneous fat, in patients with coronary artery disease. Chronic inflammation in epicardial fat may influence the pathogenesis of coronary atherosclerosis.