Nobuhiro Tahara

Clinical and Biochemical Factors Associated With Area and Metabolic Activity in the Visceral and Subcutaneous Adipose Tissues by FDG-PET/CT

CONTEXTnBody fat distribution and inflammation may play a role in metabolic derangements and cardiovascular disease in obesity.nnnOBJECTIVEnThe aim of this study is to investigate clinical and biochemical factors associated with area and metabolic activity in the visceral and subcutaneous adipose tissues (VAT and SAT).nnnPARTICIPANTSn(18)F-fluorodeoxyglucose-positron emission tomography and computed tomography imaging was performed in 251 consecutive subjects (62.6 ± 9.3 y) for risk screening.nnnMAIN OUTCOME MEASURESnWe examined which clinical, anthropometric, metabolic, and inflammatory variables including advanced glycation end products (AGEs) and pigment epithelium-derived factor (PEDF) were independently associated with area and metabolic activity in VAT and SAT. Adipose tissue area was determined with computed tomography, whereas metabolic activity was assessed by (18)F-fluorodeoxyglucose uptake expressed as a target to background ratio (TBR) of blood-normalized standardized uptake.nnnRESULTSnSerum levels of AGEs and PEDF were 9.81 ± 3.21 U/mL and 14.0 (range 10.8-17.7) μg/mL, respectively. Although the area in VAT and SAT was associated with waist circumference and sex, each adipose tissue area and TBR had different metabolic risk profiles. The TBR value in VAT was higher than that in SAT. In a multiple stepwise regression analysis, AGEs and medication for hypertension were independently associated with VAT TBR (R(2) = 0.102), whereas medication for diabetes, mean intima-media thickness, AGEs, and PEDF were the independent correlates of SAT TBR (R(2) = 0.132).nnnCONCLUSIONSnThe present study demonstrated that area and metabolic activity in VAT and SAT could be differently regulated, suggesting the involvement of AGEs and PEDF in adipose tissue inflammation.

Noninvasive Molecular Imaging of Cell Death in Myocardial Infarction using 111In-GSAO

Acute insult to the myocardium is associated with substantial loss of cardiomyocytes during the process of myocardial infarction. In this setting, apoptosis (programmed cell death) and necrosis may operate on a continuum. Because the latter is characterized by the loss of sarcolemmal integrity, we propose that an appropriately labeled tracer directed at a ubiquitously present intracellular moiety would allow non-invasive definition of cardiomyocyte necrosis. A trivalent arsenic peptide, GSAO (4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid), is capable of binding to intracellular dithiol molecules such as HSP90 and filamin-A. Since GSAO is membrane impermeable and dithiol molecules abundantly present intracellularly, we propose that myocardial localization would represent sarcolemmal disruption or necrotic cell death. In rabbit and mouse models of myocardial infarction and post-infarct heart failure, we employed In-111-labelled GSAO for noninvasive radionuclide molecular imaging. 111In-GSAO uptake was observed within the regions of apoptosis seeking agent- 99mTc-Annexin A5 uptake, suggesting the colocalization of apoptotic and necrotic cell death processes.

Efficacy and Safety of Inhaled Iloprost in Japanese Patients With Pulmonary Arterial Hypertension – Insights From the IBUKI and AIR Studies –

BACKGROUNDnInhaled iloprost is approved for pulmonary arterial hypertension (PAH) in many countries. IBUKI was a phase III, non-randomized, open-label study of the efficacy and safety of inhaled iloprost in Japanese patients with PAH.nnnMETHODSANDRESULTSnAdults with PAH who were treatment-naïve or administered endothelin receptor antagonists (ERAs) and/or phosphodiesterase type 5 inhibitors (PDE5-Is) and in NYHA/WHO functional class (FC) III/IV had inhaled iloprost (2.5 µg, increased to 5.0 µg if tolerated) 6-9 times daily for 12 weeks. Eligible patients entered a 40-week extension phase. Endpoints included change from baseline to week 12 in pulmonary vascular resistance (PVR; primary endpoint), other efficacy parameters, and safety. Data were compared with new subgroup analyses of treatment-naïve Western PAH patients from the global phase III AIR study. 27 patients received iloprost: 89% were treated with an ERA and/or PDE5-I; 70% with both. At week 12, PVR improved from baseline by -124 dyn·sec·cm(-5)(95% CI, -177 to -72) and 6-min walking distance increased by 36.0 m (95% CI, 14.9 to 57.1). NYHA/WHO FC improved in 62%; none worsened. Common drug-related adverse events were headache (37%) and cough (15%); 1 patient experienced hypotension; none reported syncope or hemoptysis. There were no deaths and no unexpected long-term safety findings. AIR PAH subgroup analyses showed similar results.nnnCONCLUSIONSnInhaled iloprost appeared effective and safe in Japanese PAH patients, including ERA- and PDE5-I-treated patients, consistent with findings of the AIR PAH subpopulation and previous iloprost studies.

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.

Positive correlation between malondialdehyde-modified low-density lipoprotein cholesterol and vascular inflammation evaluated by 18F-FDG PET/CT

OBJECTIVEnThe purpose of this study was to investigate the relationship between serum levels of malondialdehyde-modified low-density lipoprotein cholesterol (MDA-LDL) and vascular inflammation evaluated by fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT).nnnMETHODS/RESULTSnThe study involved 106 consecutive patients (75 males and 31 female, mean age 62.5 ± 7.7 years) who visited our hospital for cardiovascular risk screening and underwent carotid ultrasonography, (18)F-FDG PET/CT, complete history, physical examinations, and determination of blood chemistry including high-sensitivity C-reactive protein (hsCRP), asymmetric dimethylarginine (ADMA), and MDA-LDL. Vascular inflammation, was measured as blood-normalized standardized (18)F-FDG uptake value, known as the target-to-background ratio (TBR) of carotid arteries. Univariate and multiple stepwise regression analyses were performed for determining independent correlates of carotid TBR values. Median MDA-LDL, mean carotid TBR values and carotid intima-media thickness (IMT) were 127.5 (IQR 92.0-147.8) U/l, 1.55 ± 0.22, and 0.72 ± 0.15 mm, respectively. Univariate analysis revealed that carotid TBR values positively correlated with MDA-LDL (p = 0.043) and carotid IMT (p = 0.049). Multiple stepwise regression analysis demonstrated that MDA-LDL (p = 0.043) and carotid IMT (p = 0.038) were independently associated with carotid TBR values.nnnCONCLUSIONnThe present study reveals that serum levels of MDA-LDL are independently associated with vascular inflammation evaluated by (18)F-FDG PET/CT. Circulating MDA-LDL may be a more useful clinical biomarker for vascular inflammation within the atherosclerotic plaques than hsCRP or ADMA.

Optical frequency-domain imaging and pulmonary angioscopy in chronic thromboembolic pulmonary hypertension.

Unresolved thromboemboli in the pulmonary arteries (PAs) cause chronic thromboembolic pulmonary hypertension (CTEPH), which is usually diagnosed by mismatched perfusion defects on ventilation-perfusion lung scintigraphy and chronic thromboembolic signs on computed tomography (CT) scan and/or conventional pulmonary angiography. In our recent three cases of CTEPH (Case 1; …

Successful balloon pulmonary angioplasty with gadolinium contrast media for a patient with chronic thromboembolic pulmonary hypertension and iodine allergy

A 28-year-old male was referred to our hospital with dyspnea. He was diagnosed as having chronic thromboembolic pulmonary hypertension, and a pulmonary endarterectomy (PEA) was performed. However, exertional dyspnea remained because of residual pulmonary hypertension; therefore, the patient was re-admitted to our hospital 1 year after PEA. We performed computed tomography and pulmonary angiography and found web and band lesions in the distal pulmonary artery with a high pulmonary artery pressure. Although further management was complicated because the patient had an anaphylactic shock to iodine-based contrast media, we eventually completed five sessions of balloon pulmonary angioplasty (BPA) using gadolinium contrast medium. His symptoms and hemodynamics dramatically improved after a series of BPA. After 15 months, mean pulmonary arterial pressure reduced from 67 mmHg to 20 mmHg, and subjective symptoms improved from stage Ⅳ to I as per the WHO classification system. BPA is a potential procedure for residual pulmonary hypertension after PEA and could be safely performed using gadolinium contrast medium for patients with iodine allergy.

Efficacy and Safety of a Novel Endothelin Receptor Antagonist, Macitentan, in Japanese Patients With Pulmonary Arterial Hypertension

BACKGROUNDnMacitentan is a novel, dual endothelin receptor antagonist with sustained receptor binding, used for the long-term treatment of pulmonary arterial hypertension (PAH). In the present study, we assessed the efficacy and safety of macitentan in Japanese patients with PAH.nnnMETHODSANDRESULTSnMacitentan was administered at a once-daily dose of 10 mg in 30 patients. The primary endpoint was change in pulmonary vascular resistance (PVR) from baseline to week 24. Change to week 24 in the other hemodynamic parameters, 6-min walk distance (6MWD), World Health Organization (WHO) functional class, and plasmaN-terminal pro-brain natriuretic peptide (NT-pro-BNP), as well as time to clinical deterioration up to week 52 were also assessed as secondary endpoints. In the 28 patients on per-protocol analysis, PVR decreased from 667±293 to 417±214 dyn·sec·cm(-5)(P<0.0001). 6MWD increased from 427±128 to 494±116 m (P<0.0001). WHO functional class improved in 13 patients (46.4%) and was maintained in 15 patients (53.6%), and NT-pro-BNP was reduced by 18% (P<0.0001). The favorable treatment effect on PVR was apparent regardless of concomitant therapy for PAH.nnnCONCLUSIONSnMacitentan was efficacious and well tolerated and improved the hemodynamic parameters, exercise capacity, symptoms, and clinical biomarkers in Japanese PAH patients. Macitentan can be a valuable therapeutic option for Japanese patients with PAH. (nnnTRIAL REGISTRATIONnJAPIC Clinical Trials Information [JapicCTI-121986].) (Circ J 2016; 80: 1478-1483).

FDG-PET/CT images during 5 years before acute aortic dissection.

Since 2008, a 64-year-old man has regularly taken cancer-screening tests by combined computed tomography (CT) and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan at his own expenses ( Panels A1–A8 ). Three weeks before the last PET/CT scan (10 December 2013), he suffered from chest pain extending to his neck. The serial PET/CT scans indicated that his aortic arch has progressively enlarged ( Panels A1–A3 ; white arrowheads and A9 ; diameter of aortic arch) and that aortic FDG …

FDG-PET reveals coronary artery inflammation proceeding to cardiac allograft vasculopathy progression

A 48-year-old man with idiopathic dilated cardiomyopathy received heart transplantation on March 2005, who has undergone coronary angiography (CAG) and intravascular ultrasound (IVUS) to examine cardiac allograft vasculopathy (CAV) every 1–3 years. Although CAG has not shown significant stenoses or angiographic changes …