Munehisa Bekki

Vascular Inflammation Evaluated by [18F]-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography Is Associated With Endothelial Dysfunction

Objective—Endothelial dysfunction is an initial step in atherosclerotic cardiovascular disease. However, involvement of vascular inflammation in endothelial dysfunction is not fully investigated in humans because of the lack of diagnostic modality to noninvasively evaluate vascular inflammation. We assessed the relationship between endothelial function and vascular inflammation evaluated by [18F]-fluorodeoxyglucose-positron emission tomography/computed tomographic imaging. Approach and Results—We examined endothelial function and vascular inflammation by flow-mediated dilation (FMD) of the brachial artery and [18F]-fluorodeoxyglucose-positron emission tomography/computed tomographic imaging of carotid arteries, respectively, in 145 subjects (95 men and 50 women; mean age, 61.8±9.5 years) who underwent a risk-screening test for cardiovascular disease in Kurume University Hospital. Vascular inflammation was measured by blood-normalized standardized uptake value, known as a target:background ratio (TBR). We investigated whether absolute changes from baseline of %FMD after antihypertensive treatment for 6 months (&Dgr;%FMD) were correlated with those of TBR in 33 drug-naive patients with essential hypertension. Multiple logistic regression analysis revealed that age (odds ratio, 1.767 for 10-year increase), male sex (odds ratio, 0.434), low-density lipoprotein-cholesterol (odds ratio, 1.630 for 26-mg/dL increase), and TBR values (odds ratio, 1.759 for 0.2 increase) were independently associated with %FMD in 145 patients. There was an inverse correlation between &Dgr;%FMD and &Dgr;TBR; &Dgr;TBR was a sole independent associate of &Dgr;%FMD in hypertensive patients (r=−0.558; P<0.001). Conclusions—The present study showed that vascular inflammation in the carotid arteries evaluated by [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography was one of the independent correlates of decreased %FMD, thus suggesting the association of vascular inflammation with endothelial dysfunction in humans.

Anagliptin, A Dipeptidyl Peptidase-4 Inhibitor Ameliorates Arterial Stiffness in Association with Reduction of Remnant-Like Particle Cholesterol and Alanine Transaminase Levels in Type 2 Diabetic Patients

BACKGROUND Inhibition of dipeptidyl peptidase-4 (DPP-4) has been proposed as a therapeutic target for type 2 diabetes (T2DM). Arterial stiffness, a predictor of future cardiovascular events and all-cause mortality, is augmented in these patients. However, effects of DPP-4 inhibitors on arterial stiffness remain unknown. In this study, we compared effects of anagliptin, an inhibitor of DPP-4 on arterial stiffness evaluated by cardio-ankle vascular index (CAVI) with those of an equipotent glucose-lowering agent, glimepiride in patients with T2DM. METHODS The study involved 50 consecutive outpatients (33 males and 17 females; mean age of 72.5±9.5 years) who visited our hospitals for a risk-screening test or treatment for T2DM. They underwent complete history and physical examination, and determination of blood chemistry and anthropometric variables, and then were randomized to receive either anagliptin (n=26) or glimepiride (n=24) for 6 months. RESULTS After 6-months treatment, fasting plasma glucose and HbA1c values were comparably reduced in both groups. Anagliptin, but not glimepiride treatment significantly decreased low-density lipoprotein cholesterol, malondialdehyde-modified LDL, remnant-like particle (RLP) cholesterol, CAVI, alanine transaminase (ALT), γ-glutamyl transferase and visceral fat volume. In multiple regression analysis, absolute changes from baseline of RLP cholesterol and ALT after anagliptin treatment for 6 months (ΔRLP cholesterol and ΔALT) were independently correlated with ΔCAVI (R2=0.445). CONCLUSION The present study suggests that anagliptin may exert a beneficial effect on arterial stiffness in patients with T2DM, which is independent of its blood glucose-lowering property. Anagliptin may ameliorate arterial stiffness partly via reduction of RLP cholesterol and improvement of liver function.

Switching Dipeptidyl Peptidase-4 Inhibitors to Tofogliflozin, a Selective Inhibitor of Sodium-Glucose Cotransporter 2 Improves Arterial Stiffness Evaluated by Cardio-Ankle Vascular Index in Patients with Type 2 Diabetes: A Pilot Study

BACKGROUND We have found that anagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4) significantly ameliorates arterial stiffness in Type 2 Diabetes Mellitus (T2DM) patients compared with an equivalent hypoglycaemic agent, glimepiride. However, it remains unclear whether switching DPP-4 inhibitors to tofogliflozin, a selective inhibitor of Sodium-Glucose Cotransporter 2 (SGLT2) improves arterial stiffness in T2DM patients. METHODS Nineteen T2DM patients who had received DPP-4 inhibitors for at least 1 year were enrolled in this study. Clinical parameters and arterial stiffness evaluated by cardio-ankle vascular index (CAVI) were measured at baseline and after 6-months treatment with tofogliflozin. RESULTS At 6 months after switching to tofogliflozin, CAVI, waist circumference, body weight, body mass index, subcutaneous and visceral fat volume, white blood cell number, fasting plasma insulin, uric acid, aspartate transaminase (AST), γ-glutamyl transferase (GTP), and advanced glycation end products (AGEs) were significantly reduced, while red blood cell number, haemoglobin, and HbA1c values were increased. When stratified by median values of change in CAVI after switching to tofogliflozin (ΔCAVI), baseline serum levels of AGEs were significantly higher in the low ΔCAVI group (high responder) than in the high one (low responder). ΔAST and ΔGTP were positively correlated with ΔCAVI. CONCLUSION The present study suggests that switching DPP-4 inhibitors to tofogliflozin ameliorates arterial stiffness in T2DM patients partly via improvement of liver function. Baseline serum levels of AGEs may identify patients who improve arterial stiffness more after treatment with tofogliflozin.

Importance of extracardiac FDG uptake to diagnose cardiac sarcoidosis

Sarcoidosis is a multisystem disorder of unknown etiology, characterized by the formation of non-caseating granulomas in many organs including eye, skin, bone, muscle, nerve system, lymph node, lung, liver, and heart. Although sarcoidosis is generally recognized as having a low mortality rate, cardiac involvement could present a life-threatening situation such as conduction disturbance, ventricular tachyarrhythmia, and congestive heart failure. In 1992, the Japanese Ministry of Health and Welfare established preceding guidelines for the diagnosis of cardiac sarcoidosis (CS). Typical granulomatous myocarditis based on endomyocardial biopsy was determined as histopathologically diagnosed CS. However, endomyocardial biopsy shows the limited sensitivity no better than 30% by sampling errors due to patchy distribution of cardiac granulomas. Sarcoidosis often has been determined by extracardiac biopsy specimens from skin, muscle, and lymph node. While cardiac involvement is clinically apparent in \ 5% of all patients with sarcoidosis, over 20% of the patients have been found cardiac granulomas at autopsy. Therefore, the diagnosis of CS was often a challenging issue for physicians. In 2006, the joint committee of the Japan Society of Sarcoidosis and Other Granulomatous Disorders and the Japanese College of Cardiology modified the guidelines (Table 1). Briefly, the modified guidelines required that a histopathological or clinical diagnosis of sarcoidosis in any organs except the heart is prerequisite for evidence of sarcoidosis. If endomyocardial biopsy is negative, presence of cardiac abnormalities compatible with CS was defined as clinically diagnosed CS (Table 1). Serial electrocardiogram, 24 h Holter monitoring of electrocardiogram, echocardiography, myocardial perfusion scintigraphy, and Gallium scintigraphy can be helpful tools for clinically diagnosed CS. Especially, the revised guidelines included a positive Gallium uptake in the heart as a major criterion. However, these conventional tools are far from satisfactory for the detection of cardiac involvement. With advances in imaging technologies, the molecular targeting approach using Fluorine-fluorodeoxyglucose positron emission tomography (FDGPET) has been shown to visualize inflamed tissues and help to identify occult lesions. The shortcomings of the conventional tools stimulated the use of FDG-PET to identify and quantify granulomatous inflammation. The diagnostic approach and assessment of treatment effect in a CS patient using FDG-PET was first reported in 2002. Thereafter, FDG-PET has been employed for the assessment of granuloma localization and inflammatory activity in the heart with varying degrees of success to develop a treatment strategy in CS patients. It has been demonstrated that the focally increased FDG uptake in the heart indicates inflammatory activity within granulomas. Also, an index of heterogeneity of myocardial FDG uptake can determine the diagnosis of CS and the effect of corticosteroid therapy. Further, FDG-PET can identify individuals having a higher risk of future adverse events. However, some patients may exhibit physiological myocardial FDG uptake on PET imaging under 6-12 h of fasting conditions. Recent studies have revealed that preparation including more than 18 h of long fasting and a low-carbohydrate diet Reprint requests: Nobuhiro Tahara, MD, PhD, Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, 830-0011, Japan; ntahara@med.kurume-u.ac.jp J Nucl Cardiol 2020;27:118–22. 1071-3581/

Right ventricular workload assessed by FDG-PET in a patient with residual VSD and infundibular pulmonary stenosis after repair of tetralogy of Fallot

34.00 Copyright 2018 American Society of Nuclear Cardiology.

Myocardial metabolic improvement prior to electrocardiographic or volumetric changes of the right ventricle in pulmonary arterial hypertension.

Right ventricular workload assessed by FDG-PET in a patient with residual VSD and infundibular pulmonary stenosis after repair of tetralogy of Fallot Tomohisa Nakamura, MD, Nobuhiro Tahara, MD, PhD, Atsuko Tahara, MD, Akihiro Honda, MD, PhD, Sachiyo Igata, PhD, Munehisa Bekki, MD, Yoichi Sugiyama, MD, Jiahui Sun, MD, Eita Kumagai, MD, PhD, Seiji Kurata, MD, PhD, Kiminori Fujimoto, MD, PhD, Toshi Abe, MD, PhD, Seiya Kato, MD, PhD, Hiroyuki Tanaka, MD, PhD, and Yoshihiro Fukumoto, MD, PhD

Diagnostic performance of FDG-PET/CTA in native mitral valve endocarditis

Myocardial metabolic improvement prior to electrocardiographic or volumetric changes of the right ventricle in pulmonary arterial hypertension Tomohisa Nakamura, MD, Nobuhiro Tahara, MD, PhD, Atsuko Tahara, MD, Akihiro Honda, MD, PhD, Munehisa Bekki, MD, Yoichi Sugiyama, MD, Jiahui Sun, MD, Eita Kumagai, MD, PhD, Seiji Kurata, MD, PhD, Kiminori Fujimoto, MD, PhD, Toshi Abe, MD, PhD, Sachiyo Igata, PhD, and Yoshihiro Fukumoto, MD, PhD

Anti-inflammatory effect of statin in coronary aneurysms late after Kawasaki disease

Diagnostic performance of FDG-PET/CTA in native mitral valve endocarditis Shoko Maeda, MD, Nobuhiro Tahara, MD, PhD, Fumitake Takase, MD, Munehisa Bekki, MD, Atsuko Tahara, MD, Akihiro Honda, MD, PhD, Sachiyo Igata, PhD, Yoichi Sugiyama, MD, Tomohisa Nakamura, MD, Jiahui Sun, MD, Seiji Kurata, MD, PhD, Kiminori Fujimoto, MD, PhD, Toshi Abe, MD, PhD, Yoshihiro Fukumoto, MD, PhD a Division of Cardiovascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Japan b Department of Radiology, Kurume University School of Medicine, Kurume, Japan

Ratio of serum levels of AGEs to soluble RAGE is correlated with trimethylamine-N-oxide in non-diabetic subjects

Anti-inflammatory effect of statin in coronary aneurysms late after Kawasaki disease Munehisa Bekki, MD, Nobuhiro Tahara, MD, PhD, Atsuko Tahara, MD, Akihiro Honda, MD, PhD, Sachiyo Igata, PhD, Yoichi Sugiyama, MD, Tomohisa Nakamura, MD, Jiahui Sun, MD, Seiji Kurata, MD, PhD, Kiminori Fujimoto, MD, PhD, Toshi Abe, MD, PhD, Hiroyuki Tanaka, MD, PhD, Kenji Suda, MD, PhD, and Yoshihiro Fukumoto, MD, PhD

In Vivo Molecular Imaging of Ruptured Coronary Atherosclerotic Plaque Using IVUS, OCT, and FDG-PET/CT.

Abstract Trimethylamine (TMA), an intestinal microflora-dependent metabolite formed from phosphatidylcholine- and L-carnitine-rich food, such as red meat, is further converted to trimethylamine-N-oxide (TMAO), which could play a role in cardiometabolic disease. Red meat-derived products are one of the major environmental sources of advanced glycation end products (AGEs) that may also contribute to the pathogenesis of cardiometabolic disorders through the interaction with receptor for AGEs (RAGE). However, the relationship among AGEs, soluble form of RAGE (sRAGE) and TMAO in humans remains unclear. Non-diabetic subjects underwent a physical examination, determination of blood chemistry and anthropometric variables, including AGEs, sRAGE, TMA and TMAO. Multiple regression analyses revealed that HbA1c, uric acid and AGEs were independently associated with log TMA, whereas log AGEs to sRAGE ratio and statin non-use were independently correlated with log TMAO. Our present findings indicated that AGEs to sRAGE ratio was correlated with log TMAO, a marker of cardiometabolic disorders.