Researcher Database

Masanao Naya
Hokkaido University Hospital Internal Medicine
Lecturer

Researcher Profile and Settings

Affiliation

  • Hokkaido University Hospital Internal Medicine

Job Title

  • Lecturer

J-Global ID

Research Interests

  • 心臓CT   心臓MRI   心不全   希少心疾患   Coronary flow reserve   Cardiac sarcoidosis   Coronary artery diseasee   循環器   核医学(PETを含む)   冠血管内皮機能   心筋血流量   

Research Areas

  • Life sciences / Cardiology

Academic & Professional Experience

  • 2012 - Today Hokkaido University
  • 2009/10 - 2011/10 Harvard University

Association Memberships

  • JAPANESE ASSOCIATION OF CARDIOVASCULAR INTERVENTION AND THERAPEUTICS   日本心臓核医学学会   日本放射線学会   JAPANESE SOCIETY OF NUCLEAR MEDICINE   THE JAPANESE SOCIETY OF INTERNAL MEDICINE   The Japanese Circulation Society   

Research Activities

Published Papers

  • Shiro Miura, Osamu Manabe, Masanao Naya, Akira Ando, Atsushi Usami, Chihoko Miyazaki, Ohkusa Takanori, Takehiro Yamashita
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 2020/08/06 [Refereed][Not invited]
  • Kazuhiro Koyanagawa, Masanao Naya, Osamu Manabe, Toshihisa Anzai
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 27 (3) 719 - 722 2020/06 [Refereed][Not invited]
  • Osamu Manabe, Kazuhiro Koyanagawa, Kenji Hirata, Noriko Oyama-Manabe, Hiroshi Ohira, Tadao Aikawa, Sho Furuya, Masanao Naya, Ichizo Tsujino, Yuuki Tomiyama, Yuka Otaki, Toshihisa Anzai, Nagara Tamaki
    JACC. Cardiovascular imaging 13 (4) 1096 - 1097 2020/04 [Refereed][Not invited]
  • Eigo Kurebayashi, Osamu Manabe, Masanao Naya, Shiro Miura, Takehiro Yamashita, Yoshihiro Imai, Akira Ando, Chihoko Miyazaki, Toshihisa Anzai
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 27 (1) 326 - 329 1071-3581 2020/02 [Refereed][Not invited]
  • Tadao Aikawa, Masanao Naya, Kazuhiro Koyanagawa, Osamu Manabe, Masahiko Obara, Keiichi Magota, Noriko Oyama-Manabe, Nagara Tamaki, Toshihisa Anzai
    European heart journal cardiovascular Imaging 21 (1) 36 - 46 2047-2404 2020/01/01 [Refereed][Not invited]
     
    AIMS: Myocardial perfusion imaging without and with quantitative myocardial blood flow (MBF) and myocardial flow reserve (MFR) plays an important role in the diagnosis and risk stratification of patients with stable coronary artery disease (CAD). We aimed to quantify the effects of coronary revascularization on regional stress MBF and MFR and to determine whether the presence of subendocardial infarction was associated with these changes. METHODS AND RESULTS: Forty-seven patients with stable CAD were prospectively enrolled. They underwent 15O-water positron emission tomography at baseline and 6 months after optimal medical therapy alone (n = 16), percutaneous coronary intervention (PCI) (n = 18), or coronary artery bypass grafting (CABG) (n = 13). Stenosis of ≥50% diameter was detected in 98/141 vessels (70%). The regional MFR was significantly increased from baseline to follow-up [1.84 (interquartile range, IQR 1.28-2.17) vs. 2.12 (IQR 1.69-2.63), P < 0.001] in vessel territories following PCI or CABG due to an increase in the stress MBF [1.33 (IQR 0.97-1.67) mL/g/min vs. 1.64 (IQR 1.38-2.17) mL/g/min, P < 0.001], whereas there was no significant change in the regional stress MBF or MFR in vessel territories without revascularization. A multilevel mixed-effects models adjusted for baseline characteristics, subendocardial infarction assessed by cardiovascular magnetic resonance imaging, and intra-patient correlation showed that the degree of angiographic improvement after coronary revascularization was significantly associated with increased regional stress MBF and MFR (P < 0.05 for all). CONCLUSION: Coronary revascularization improved the regional stress MBF and MFR in patients with stable CAD. The magnitude of these changes was associated with the extent of revascularization independent of subendocardial infarction.
  • Shiro Miura, Masanao Naya, Osamu Manabe, Akira Ando, Atsushi Usami, Chihoko Miyazaki, Takehiro Yamashita, Youhei Ohkawa
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 1071-3581 2019/12/24 [Refereed][Not invited]
  • Sho Furuya, Masanao Naya, Osamu Manabe, Kenji Hirata, Hiroshi Ohira, Tadao Aikawa, Kazuhiro Koyanagawa, Keiichi Magota, Ichizo Tsujino, Toshihisa Anzai, Yuji Kuge, Noriko Oyama-Manabe, Kohsuke Kudo, Tohru Shiga, Nagara Tamaki
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 1071-3581 2019/12/09 [Refereed][Not invited]
     
    BACKGROUND: 18F-fluoromisonidazole (FMISO) is a hypoxia positron emission tomography (PET) tracer. Here, we evaluated cardiac and extra-cardiac sarcoidosis using both FMISO and 18F-fluorodeoxyglucose (FDG) PET/CT in a prospective cohort of patients with sarcoidosis. METHODS: Ten consecutive sarcoidosis patients with suspected cardiac involvement were prospectively enrolled. Each patient fasted overnight (for ≥ 18 hours) preceded by a low-carbohydrate diet before FDG PET/CT but not given special dietary instructions before the FMISO PET/CT scan. We visually and semiquantitatively assessed the uptakes of FMISO and FDG using the maximal standardized uptake value (SUVmax). The metabolic volume (MV) of FDG was calculated as the volume within the boundary determined by the threshold (mean SUV of blood pool × 1.5). RESULTS: Nine patients showed focal FDG uptake in the myocardium and were diagnosed with cardiac sarcoidosis. Among the patients with extra-cardiac lesions, FDG uptake was seen in 8 lymph nodes and 3 lung lesions. FMISO uptake was seen in the 7 cardiac (77.8%) and 6 extra-cardiac (54.5%) lesions. None of the patients showed physiological FMISO uptake in the myocardium. The SUVmax values of the lesions with FMISO uptake were higher than those of the lesions without FMISO uptake in both the cardiac (SUVmax: 9.9, IQR: 8.4-10.0 vs 7.3, IQR: 6.3-8.2) and non-cardiac lesions (SUVmax: 17.6, IQR: 14.5-19.3 vs 6.1, IQR: 5.9-6.2; P = 0.006). The MV values of the lesions with FMISO uptake were significantly higher than those of the lesions without FMISO uptake (111.3, IQR: 78.3-135.7 vs 6.4, IQR: 1.9-23.3; P = 0.0009). CONCLUSIONS: FMISO showed no physiological myocardial uptake and did not require special preparation. FMISO PET has the potential to detect hypoxic lesions in patients with sarcoidosis.
  • Shiro Miura, Masanao Naya, Takehiro Yamashita, Youhei Ohkawa
    European heart journal. Case reports 3 (4) 1 - 5 2019/12 [Refereed][Not invited]
     
    Background: Prosthetic valve endocarditis (PVE) is a life-threatening systemic infection involving a high mortality rate and severe complications, including perivalvular abscess. Early diagnosis and detection of PVE continue to be challenging in clinical settings. Case summary: A 64-year-old man with a history of mechanical aortic valve implantation 12 years prior was referred to our hospital with a major complaint of high fever and was admitted. Although results of three blood culture tests at admission were negative, transthoracic echocardiography, and transoesophageal echocardiography (TOE) were performed to exclude the possibility of PVE; both, however, were inconclusive. Subsequently, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) was performed; revealing intense hyper-metabolism above the aortic valve prosthesis with a greater intensity at the posterior end, confirming a diagnosis of aortic PVE complicated with perivalvular abscess. Discussion: Considering the intermediate suspicion of PVE despite negative TOE and negative blood culture tests, 18F-FDG PET/CT can play a central role in diagnosing PVE. However, this new imaging modality often fails to differentiate thrombi, soft atherosclerotic plaques, or foreign body reactions on the surface of prosthetic valves. In this report, we have successfully enhanced the diagnostic accuracy of 18F-FDG PET/CT by focusing on perivalvular involvement, which could be a key finding, because intense 18F-FDG uptake surrounding the aortic annulus was consistent with the thickened area within the aortic annular region observed in the TOE examinations.
  • Kazuhiro Koyanagawa, Masanao Naya, Tadao Aikawa, Osamu Manabe, Sho Furuya, Masato Kuzume, Noriko Oyama-Manabe, Hiroshi Ohira, Ichizo Tsujino, Toshihisa Anzai
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 1071-3581 2019/10/11 [Refereed][Not invited]
     
    BACKGROUND: Sarcoidosis is a multisystemic disorder of unknown cause characterized by immune granuloma formation in the involved organs. Few studies have reported on the myocardial perfusion changes by immunosuppression therapy in cardiac sarcoidosis (CS). Additionally, the relationship between myocardial perfusion changes and prognosis is unknown. Therefore, this study aimed to clarify myocardial perfusion recovery after steroid therapy and its prognostic value for major adverse cardiac events (MACE) in patients with CS. METHODS AND RESULTS: Thirty-eight consecutive patients with CS {median age, 63 [interquartile range (IQR) 51-68] years; 10 men} underwent both 18F-fluorodeoxyglucose positron emission tomography/computed tomography (CT) and electrocardiography-gated single-photon emission CT (SPECT) pre- and post-steroid therapy. Patients with improved or preserved myocardial perfusion after post-therapy were defined as the recovery group and those with worsened myocardial perfusion as the non-recovery group. Twenty-six patients (68%) were categorized as the recovery group. MACE occurred in eight patients. The Kaplan-Meier curves revealed a significantly higher rate of MACE in the non-recovery group (17.4%/y vs 2.9%/y, P = 0.007). CONCLUSIONS: Myocardial perfusion was recovered by steroid therapy in 61% and preserved in 8% of patients. Myocardial perfusion recovery after steroid therapy was significantly associated with a low incidence of MACE.
  • FDG PETのテクスチャ解析を用いた心臓サルコイドーシスの予後検討
    真鍋 治, 平田 健司, 真鍋 徳子, 古家 翔, 小梁川 和宏, 大平 洋, 相川 忠夫, 納谷 昌直, 辻野 一三, 玉木 長良, 志賀 哲
    核医学 56 (Suppl.) S137 - S137 0022-7854 2019/10 [Refereed][Not invited]
  • 心筋サルコイドーシスにおける心筋血流の改善から予想される心イベントの減少化(Improvement in myocardial perfusion predicts fewer cardiac events in cardiac sarcoidosis)
    小梁川 和宏, 納谷 昌直, 相川 忠夫, 真鍋 治, 古家 翔, 葛目 将人, 真鍋 徳子, 大平 洋, 辻野 一三, 安斉 俊久
    核医学 56 (Suppl.) S137 - S137 0022-7854 2019/10 [Refereed][Not invited]
  • 心臓サルコイドーシス評価のFDG-PET/CT撮像にヘパリン注射は必要か?
    古家 翔, 真鍋 治, 大平 洋, 納谷 昌直, 相川 忠夫, 小梁川 和宏, 辻野 一三, 真鍋 徳子[大山], 平田 健司, 志賀 哲
    核医学 (一社)日本核医学会 56 (Suppl.) S137 - S137 0022-7854 2019/10 [Refereed][Not invited]
  • Osamu Manabe, Masanao Naya, Noriko Oyama-Manabe, Kazuhiro Koyanagawa, Nagara Tamaki
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 26 (5) 1602 - 1616 1071-3581 2019/10 [Refereed][Not invited]
     
    Takotsubo cardiomyopathy (TC) is a syndrome of transient left ventricular (LV) dysfunction mimicking acute coronary syndrome. Although the mechanisms underlying the occurrence of TC are unknown, several imaging techniques contribute to its diagnosis. Here we review the current knowledge about TC, in particular, the pathophysiology and the role of imaging including nuclear cardiovascular medicine.
  • Yumi Takahashi, Hiroyuki Iwano, Ippei Nakano, Arata Fukushima, Masanao Naya, Ai Shimizu, Yoshihiro Matsuno, Noriko Oyama-Manabe, Toshihisa Anzai
    Internal medicine (Tokyo, Japan) 58 (17) 2539 - 2543 0918-2918 2019/09/01 [Refereed][Not invited]
     
    Although cardiac involvement is rare in polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome, the clinical course becomes considerably worse on complication with cardiac lesions. The increased release of various cytokines has been observed in the pathogenesis of POEMS syndrome, and serum vascular endothelial growth factor (VEGF) levels are known to be associated with the disease activity. We herein report a patient with POEMS syndrome who showed left ventricular systolic dysfunction and was treated with lenalidmide therapy. Of note, the reduction in extracellular edema in the left ventricular wall was clearly visualized by changes in the native T1 values and extracellular volumes on cardiac magnetic resonance imaging.
  • F-18 fluoromisonidazole(FMISO)PET/CTによるサルコイドーシスの低酸素病変の評価
    古家 翔, 真鍋 治, 納谷 昌直, 大平 洋, 相川 忠夫, 小梁川 和宏, 孫田 恵一, 真鍋 徳子, 久下 裕司, 志賀 哲
    日本心臓核医学会ニュースレター 日本心臓核医学会 21 (2) 22 - 22 1346-2733 2019/06 [Refereed][Not invited]
  • 冠血行再建治療後の局所心筋血流量と心筋血流予備能の改善メカニズム 15O標識水PETと心臓MRIを用いた検討
    相川 忠夫, 納谷 昌直, 小梁川 和宏, 真鍋 治, 真鍋 徳子, 玉木 長良, 安斉 俊久
    日本心臓核医学会ニュースレター 日本心臓核医学会 21 (2) 96 - 96 1346-2733 2019/06 [Refereed][Not invited]
  • 心臓サルコイドーシスにおけるステロイド治療後の心筋血流改善は心血管イベントの低発症率を予測する
    小梁川 和宏, 納谷 昌直, 相川 忠夫, 真鍋 治, 真鍋 徳子, 古家 翔, 辻野 一三, 大平 洋
    日本心臓核医学会ニュースレター 日本心臓核医学会 21 (2) 124 - 124 1346-2733 2019/06 [Refereed][Not invited]
  • Kumita S, Yoshinaga K, Miyagawa M, Momose M, Kiso K, Kasai T, Naya M, Committee for, diagnosis of cardiac, sarcoidosis using, F-FDG PET, Japanese, Society of Nuclear Cardiology
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 1071-3581 2019/06 [Refereed][Not invited]
  • Osamu Manabe, Markus Kroenke, Tadao Aikawa, Atsuto Murayama, Masanao Naya, Atsuro Masuda, Noriko Oyama-Manabe, Kenji Hirata, Shiro Watanabe, Tohru Shiga, Chietsugu Katoh, Nagara Tamaki
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 26 (3) 909 - 918 1071-3581 2019/06 [Refereed][Not invited]
     
    OBJECTIVE: FDG PET/CT plays a significant role in the diagnosis of inflammatory heart diseases and cardiac tumors. We attempted to determine the optimal FDG uptake threshold for volume-based analyses and to evaluate the relationship between the myocardial physiological uptake volume in FDG PET and several clinical factors. METHODS: A total of 190 patients were retrospectively analyzed. The cardiac metabolic volume (CMV) was defined as a volume within the boundary determined by a threshold (SUVmean of blood pool × 1.5). RESULTS: The SUVmean of the blood pool measured in the descending aorta (DA) (r = 0.86, intraclass correlation coefficient [ICC] = 0.93, P < 0.0001) and that in the left ventricle (LV) cavity (r = 0.87, ICC = 0.90, P < 0.0001) showed high inter-operator reproducibility. However, the SUVmean in the LV cavity showed a significant correlation with the CMV (P = 0.0002, r = 0.26). The CMV in the patients who fasted < 18 hours were significantly higher (49.7  ±  73.2 vs. 18.0  ±  53.8 mL, P = 0.0013) compared to the patients with > 18-hour fasting. The multivariate analysis demonstrated that only the fasting period > 18 hours was independently associated with CMV = 0. CONCLUSION: Our findings revealed that the DA is suitable to decide the threshold for the volume-based analysis. The fasting time was significantly associated with the cardiac FDG uptake.
  • Osamu Manabe, Hiroshi Ohira, Kenji Hirata, Souichiro Hayashi, Masanao Naya, Ichizo Tsujino, Tadao Aikawa, Kazuhiro Koyanagawa, Noriko Oyama-Manabe, Yuuki Tomiyama, Keiichi Magota, Keiichiro Yoshinaga, Nagara Tamaki
    European journal of nuclear medicine and molecular imaging 46 (6) 1240 - 1247 1619-7070 2019/06 [Refereed][Not invited]
     
    PURPOSE: 18F-fluorodeoxyglocose positron emission tomography (FDG PET) plays a significant role in the diagnosis of cardiac sarcoidosis (CS). Texture analysis is a group of computational methods for evaluating the inhomogeneity among adjacent pixels or voxels. We investigated whether texture analysis applied to myocardial FDG uptake has diagnostic value in patients with CS. METHODS: Thirty-seven CS patients (CS group), and 52 patients who underwent FDG PET/CT to detect malignant tumors with any FDG cardiac uptake (non-CS group) were studied. A total of 36 texture features from the histogram, gray-level co-occurrence matrix (GLCM), gray-level run length matrix (GLRLM), gray-level zone size matrix (GLZSM) and neighborhood gray-level difference matrix (NGLDM), were computed using polar map images. First, the inter-operator and inter-scan reproducibility of the texture features of the CS group were evaluated. Then, texture features of the patients with CS were compared to those without CS lesions. RESULTS: Twenty-eight of the 36 texture features showed high inter-operator reproducibility with intraclass correlation coefficients (ICCs) over 0.80. In addition, 17 of the 36 showed high inter-scan reproducibility with ICCs over 0.80. The SUVmax showed no difference between the CS and non-CS group [7.36 ± 2.77 vs. 8.78 ± 4.65, p = 0.45, area under the curve (AUC) = 0.60]. By contrast, 16 of the 36 texture features could distinguish CS from non-CS grsoup with AUC > 0.80. Multivariate logistic regression analysis after hierarchical clustering concluded that long-run emphasis (LRE; P = 0.0004) and short-run low gray-level emphasis (SRLGE; P = 0.016) were significant independent factors that could distinguish between the CS and non-CS groups. Specifically, LRE was significantly higher in CS than in non-CS (30.1 ± 25.4 vs. 11.4 ± 4.6, P < 0.0001), with high diagnostic ability (AUC = 0.91), and had high inter-operator reproducibility (ICC = 0.98). CONCLUSIONS: The texture analysis had high inter-operator and high inter-scan reproducibility. Some of texture features showed higher diagnostic value than SUVmax for CS diagnosis. Therefore, texture analysis may have a role in semi-automated systems for diagnosing CS.
  • Kato T, Uemura Y, Naya M, Momose M, Matsumoto N, Suzuki E, Hida S, Nakajima T, Yamauchi T, Tamaki N
    Scientific reports 9 (1) 7882  2019/05 [Refereed][Not invited]
  • Yasuka Kikuchi, Masanao Naya, Noriko Oyama-Manabe, Osamu Manabe, Hiroyuki Sugimori, Kohsuke Kudo, Fumi Kato, Tadao Aikawa, Hiroyuki Tsutsui, Nagara Tamaki, Hiroki Shirato
    Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine 18 (2) 134 - 141 1347-3182 2019/04/10 [Refereed][Not invited]
     
    PURPOSE: The aim of this study was to verify coronary flow velocity reserve (CFVR) on the left main trunk (LMT) in comparison with myocardial flow reserve (MFR) by 15O-labeled water positron emission tomography (PET) (MFR-PET) in both the healthy adults and the patients with coronary artery disease (CAD), and to evaluate the feasibility of CFVR to detect CAD. METHODS: Eighteen healthy adults and 13 patients with CAD were evaluated. CFVR in LMT was estimated by 3T magnetic resonance imaging (MRI) with phase contrast technique. MFR-PET in the LMT territory including anterior descending artery and circumflex artery was calculated as the ratio of myocardial blood flow (MBF)-PET at stress to MBF-PET at rest. RESULTS: There was a significant positive relationship between CFVR and MFR-PET (R = 0.45, P < 0.0001). Inter-observer calculations of CFVR showed good correlation (R2 = 0.93, P < 0.0001). The CFVR in patients with CAD was significantly lower than that in healthy adults (1.90 ± 0.61 vs. 2.77 ± 1.03, respectively, P = 0.01), which were similar to the results of MFR-PET (2.23 ± 0.84 vs. 3.96 ± 1.04, respectively, P < 0.0001). For the detection of patients with CAD, the area under the curve was 0.78 (P = 0.01). The sensitivity was 0.77 and specificity was 0.72 when a cut-off of 2.15 was used. CONCLUSION: CFVR by 3T was validated with MFR-PET. CFVR could detect the patients with CAD. This method is a simple and reliable index without radiation or contrast material.
  • Nagashima K, Hiro T, Fukamachi D, Okumura Y, Watanabe I, Hirayama A, Tanaka M, Tanaka T, Takamisawa I, Taguchi I, Sato A, Aonuma K, Fukamizu S, Nakada A, Watanabe A, Amioka N, Suzuki Y, Matsumoto N, Koizumi J, Kumagai K, Naya M, Higuchi Y, Naito Y, Masuyama T, Kawamura M, Tsunoda R, Suzuki S, Ishii H, Murohara T, Shimizu T, Takeishi Y, Shiina K, Yamashita J, Imamura T, Sumitomo N, Noguchi T, Aso T, Furukawa K, Yamauchi Y, Okishige K, Sakata K, Yamagishi M, Shimizu S, Ohno M, Sugano T, Matsumura K, Matsumoto K, Ozaki K, Hayashidani S, Meno H, Iwata A, Higuma T, Tomita H, Yoshino H, Taniai S, Shishido K, Murakami M, Negishi K, Nii M, Wakatsuki D, Suzuki H, Motoike Y, Ozaki Y, Nakazato J, Hayashi H, Higuchi S, Shoda M
    European heart journal cardiovascular Imaging 2047-2404 2019/04 [Refereed][Not invited]
  • 心血管疾患の非侵襲評価および定量的評価における現在の試み 心血管画像診断のためのハートチームのアプローチ(Our Current Efforts on Noninvasive and Quantitative Assessment of Cardiovascular Disease: A Heart Team Approach for Cardiovascular Imaging)
    相川 忠夫, Naya Masanao, Oyama-Manabe Noriko, Koyanagawa Kazuhiro, Manabe Osamu, Anzai Toshihisa
    日本循環器学会学術集会抄録集 83回 RT4 - 2 2019/03 [Refereed][Not invited]
  • 冠血行再建術がPET CTで評価する局所心筋血流予備能に与える影響(The Impact of Coronary Revascularization on Regional Myocardial Flow Reserve Assessed by Positron Emission Tomography)
    相川 忠夫, 納谷 昌直, 小梁川 和宏, 真鍋 治, 真鍋 徳子, 安斉 俊久
    日本循環器学会学術集会抄録集 83回 PJ103 - 2 2019/03 [Refereed][Not invited]
  • Kazuhiro Koyanagawa, Masanao Naya, Tadao Aikawa, Osamu Manabe, Masato Kuzume, Hiroshi Ohira, Ichizo Tsujino, Nagara Tamaki, Toshihisa Anzai
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 1071-3581 2019/02/27 [Refereed][Not invited]
     
    BACKGROUND: We aimed to determine the correlation between phase analysis, reflecting the heterogeneity of perfusion defects, and the dyssynchrony of the left ventricle wall motion, and adverse cardiac events in cardiac sarcoidosis (CS) patients. METHODS: Fifty-seven consecutive patients with diagnosed CS (64 [IQR 55-71] years old, 14 males), who underwent 18F-FDG PET/CT and ECG-gated SPECT, were studied. FDG PET was analysed to measure cardiac metabolic volume (CMV), and total lesion glycolysis (TLG). The SPECT findings, such as LVEF, Summed Rest Score (SRS), bandwidth (BW) were evaluated. RESULTS: The median of BW was 56° (IQR 40-95). BW showed a strong inverse correlation with LVEF (r = - 0.60, P < 0.0001), and positive correlation with SRS (r = 0.82, P < 0.0001). However, there were no significant correlations between BW and CMV or TLG. The Kaplan-Meier curves revealed a significantly higher rate of MACE in the high BW group (BW > 56°) than the low BW group (BW ≤ 56°) (15.1%/years vs. 4.4%/years, P = 0.025). In multivariable analysis, BW was a significant independent predictor of MACE (P = 0.015). CONCLUSION: Phase analysis on gated SPECT was a significant and independent predictor of MACE in patients with CS.
  • Tadao Aikawa, Atsuhito Takeda, Noriko Oyama-Manabe, Masanao Naya, Hirokuni Yamazawa, Kazuhiro Koyanagawa, Yoichi M Ito, Toshihisa Anzai
    Pediatric cardiology 40 (2) 384 - 392 0172-0643 2019/02 [Refereed][Not invited]
     
    This study examined the progression of left ventricular dysfunction and myocardial fibrosis in patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) to evaluate the effects of angiotensin-converting enzyme inhibitor (ACEI). Ninety-eight cardiovascular magnetic resonance (CMR) studies in 34 consecutive patients with DMD (n = 21) or BMD (n = 13) were retrospectively reviewed. Left ventricular ejection fraction (LVEF) and the extent of myocardial late gadolinium enhancement (LGE) were semiautomatically quantified. During the study period, five patients had already been treated with ACEI at the first CMR; five were started on ACEI at LVEF ≥ 55% and 10 at LVEF < 55%. All patients had hyperenhanced myocardium on LGE images at the first CMR (median extent, 3.3%; interquartile range 0.1-14.3%). A mixed-effects model for longitudinal data of each patient, adjusted for age, type of muscular dystrophy, steroid use, and ACEI use showed that higher age (β = - 1.1%/year; 95% confidence interval [CI], - 1.8% to - 0.4%; p = 0.005) and no use of ACEI (β = - 3.1%; 95% CI, - 5.4% to - 0.8%; p = 0.009) were significantly associated with a lower LVEF. When ACEI use was stratified by time of initiation (LVEF ≥ 55% vs. < 55%), only ACEI initiation at LVEF < 55% had a beneficial effect on LVEF at each imaging examination (β = 3.7%; 95% CI, 0.9-6.4%; p = 0.010). ACEI use or the time of initiation of ACEI did not significantly affect age-related increase in LGE. ACEI attenuated the age-related decline in LVEF only in patients with DMD or BMD and reduced LVEF, suggesting that further investigation on prophylactic use of cardioprotective therapy in these patients is warranted.
  • Masanao Naya, Osamu Manabe, Nagara Tamaki
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 1071-3581 2019/02/01 [Refereed][Not invited]
  • Kazunori Omote, Masanao Naya, Kazuhiro Koyanagawa, Tadao Aikawa, Osamu Manabe, Toshiyuki Nagai, Kiwamu Kamiya, Yoshiya Kato, Hirokazu Komoriyama, Masato Kuzume, Nagara Tamaki, Toshihisa Anzai
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 1071-3581 2019/01/04 [Refereed][Not invited]
     
    BACKGROUND: The aim of this study was to determine whether right ventricle (RV) 18F-fluorodeoxyglucose (FDG) uptake can predict positive findings of endomyocardial biopsy (EMB) in patients with cardiac sarcoidosis (CS). METHODS: 70 consecutive patients with clinically diagnosed CS who had undergone FDG PET were registered in the present study. Patients without EMB (n = 42) were excluded. Ultimately, 28 patients were studied. EMB samples were obtained from the RV septum. We evaluated the FDG uptake on six segments (RV, left ventricle anterior, septal, lateral, inferior, and apex). RESULTS: Positive EMB was found in six patients (21%). Patients were divided into two groups according to positive (n = 12 [43%]) or negative (n = 16 [57%]) RV FDG uptake. Patients with positive RV FDG uptake had a significantly higher frequency of positive EMB than those without (42% vs. 6%, P = 0.024). On the other hand, there was no EMB-predictive value for the FDG uptakes in the other five segments, the cardiac metabolic volume, total lesion glycolysis, left ventricular ejection fraction, or any electrocardiogram findings. CONCLUSIONS: FDG uptake of the RV but no other heart segment was associated with positive EMB in CS patients. The presence of RV FDG uptake could improve the rate of positive EMB up to 42% in patients with CS.
  • Oyama-Manabe Noriko, Manabe Osamu, Naya Masanao, Kudo Kohsuke, Tamaki Nagara
    Annals of Nuclear Cardiology 日本心臓核医学会 5 (1) 79 - 83 2189-3926 2019 [Refereed][Not invited]
     
    Cardiac computed tomography (CT) could provide the comprehensive morphologic and functional information of coronary artery disease. Coronary CT angiography has been well established for identification and management of symptomatic patients with or suspected coronary artery disease. However, we should know the anatomical stenosis is not the same as the functional one needed to be treated. Dynamic perfusion imaging could lead a non-invasive quantitative evaluation of myocardial ischemia with estimation of myocardial blood flow. In this review, we address the characteristics and advantages of cardiac CT, in particular dynamic perfusion CT for quantitative evaluation of myocardial ischemia.
  • Tadao Aikawa, Masanao Naya, Masahiko Obara, Osamu Manabe, Keiichi Magota, Kazuhiro Koyanagawa, Naoya Asakawa, Yoichi M Ito, Tohru Shiga, Chietsugu Katoh, Toshihisa Anzai, Hiroyuki Tsutsui, Venkatesh L Murthy, Nagara Tamaki
    Cardiovascular research 115 (1) 119 - 129 0008-6363 2019/01/01 [Refereed][Not invited]
     
    Aims: Coronary flow reserve (CFR) is an integrated measure of the entire coronary vasculature, and is a powerful prognostic marker in coronary artery disease (CAD). The extent to which coronary revascularization can improve CFR is unclear. This study aimed to evaluate the impact of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) on CFR in patients with stable CAD. Methods and results: In a prospective, multicentre observational study, CFR was measured by 15O-water positron emission tomography as the ratio of stress to rest myocardial blood flow at baseline and 6 months after optimal medical therapy (OMT) alone, PCI, or CABG. Changes in the SYNTAX and Leaman scores were angiographically evaluated as indicators of completeness of revascularization. Follow-up was completed by 75 (25 OMT alone, 28 PCI, and 22 CABG) out of 82 patients. The median SYNTAX and Leaman scores, and baseline CFR were 14.5 [interquartile range (IQR): 8-24.5], 5.5 (IQR: 2.5-12.5), and 1.94 (IQR: 1.67-2.66), respectively. Baseline CFR was negatively correlated with the SYNTAX (ρ = -0.40, P < 0.001) and Leaman scores (ρ = -0.33, P = 0.004). Overall, only CABG was associated with a significant increase in CFR [1.67 (IQR: 1.14-1.96) vs. 1.98 (IQR: 1.60-2.39), P < 0.001]. Among patients with CFR <2.0 (n = 41), CFR significantly increased in the PCI [1.70 (IQR: 1.42-1.79) vs. 2.21 (IQR: 1.78-2.49), P = 0.002, P < 0.001 for interaction between time and CFR] and CABG groups [1.28 (IQR: 1.13-1.80) vs. 1.86 (IQR: 1.57-2.22), P < 0.001]. The reduction in SYNTAX or Leaman scores after PCI or CABG was independently associated with the percent increase in CFR after adjusting for baseline characteristics (P = 0.012 and P = 0.011, respectively). Conclusion: Coronary revascularization ameliorated reduced CFR in patients with obstructive CAD. The degree of improvement in angiographic CAD burden by revascularization was correlated with magnitude of improvement in CFR.
  • Masanao Naya, Osamu Manabe, Kazuhiro Koyanagawa, Nagara Tamaki
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 25 (6) 1980 - 1987 1071-3581 2018/12 [Refereed][Not invited]
     
    Radionuclide imaging has an advantage for quantitative analyses of the tracer concentration and its temporal changes. Myocardial perfusion and function have been adapted for synchrony analyses. Extracted parameters have been demonstrated to measure ventricular synchrony and even to predict CRT outcomes. ERNA has the advantages of higher temporal resolution, greater reproducibility, and the volumetric analysis of both ventricles that can be applied for analyses of intraventricular synchrony and interventricular synchrony. Several software packages such as Quantitative Gated SPECT, the Emory Cardiac Toolbox, cardioREPO, and Heart Function View are available to assess the LV dyssynchrony parameters from GSPECT. A count-based method is applied to extract the amplitude and phase from each of the reconstructed GSPECT short-axis datasets throughout the cardiac cycle and then subjected to a Fourier analysis, the results of which are displayed on a polar map and histogram. Some of the parameters such as the bandwidth (expressed as the 95% width of the phase histogram) and the standard deviation of the phase are obtained by the phase histogram to assess the intraventricular synchrony. This review paper focuses on the application of the LV dyssynchrony parameters estimated by cardiac SPECT in patients with a heart disease.
  • Masanao Naya, Osamu Manabe, Kazuhiro Koyanagawa, Nagara Tamaki
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 25 (6) 1988 - 1989 1071-3581 2018/12 [Refereed][Not invited]
     
    Some of the values in Table 3 of the original publication inadvertently contained discrepancies with the literature from which they were taken. A corrected version of Table 3 can be found below; the values which have been corrected now appear in bold text (row: Romero-Farina G).
  • 冠動脈疾患患者において血清TBARSは冠微小循環障害の予測因子である
    納谷 昌直, 相川 忠夫, 小原 雅彦, 真鍋 治, 小梁川 和宏, 浅川 直也, 加藤 知恵次, 鈴木 えり子, 筒井 裕之, 玉木 長良, 安斉 俊久
    核医学 (一社)日本核医学会 55 (Suppl.) S191 - S191 0022-7854 2018/11 [Refereed][Not invited]
  • 15O-水心筋血流PETにおけるMonte Carlo scaling複合型SSS散乱補正の検討
    孫田 惠一, 志賀 哲, 真鍋 治, 納谷 昌直, 相川 忠夫, 新山 大樹, 平田 健司, 加藤 千恵次, 藤田 勝久, 玉木 長良
    核医学 (一社)日本核医学会 55 (Suppl.) S212 - S212 0022-7854 2018/11 [Refereed][Not invited]
  • FMISO-PETによる心臓サルコイドーシス病変の評価
    古家 翔, 真鍋 治, 大平 洋, 納谷 昌直, 相川 忠夫, 小梁川 和宏, 渡邊 史郎, 小林 健太郎, 平田 健司, 志賀 哲, 真鍋 徳子
    核医学 (一社)日本核医学会 55 (Suppl.) S233 - S233 0022-7854 2018/11 [Refereed][Not invited]
  • Naya M, Uemura Y, Matsumoto N, Momose M, Kato T, Hida S, Yamauchi T, Nakajima T, Suzuki E, Tamaki N, J-COMPASS Extended Follow-Up, Study Group
    Coronary artery disease 29 (7) 539 - 546 0954-6928 2018/11 [Refereed][Not invited]
  • Sho Furuya, Osamu Manabe, Hiroshi Ohira, Kenji Hirata, Tadao Aikawa, Masanao Naya, Ichizo Tsujino, Kazuhiro Koyanagawa, Toshihisa Anzai, Noriko Oyama-Manabe, Tohru Shiga
    EJNMMI research 8 (1) 94 - 94 2018/10/05 [Refereed][Not invited]
     
    BACKGROUND: Cardiac sarcoidosis (CS) is a rare but potentially life-threatening disease that causes conduction disturbance, systolic dysfunction, and, most notably, sudden cardiac death. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) plays important roles not only in diagnosing CS but also in evaluating the effects of anti-inflammatory therapy. A volume-based analysis of parameters measured by FDG PET, so-called cardiac metabolic volume (CMV), has emerged as a new assessment tool. CMV is measured as the volume within the boundary determined by a reference tissue such as the liver and the blood pool uptake. However, there is a possibility that oral steroid therapy could lead to variations of the liver and the blood pool uptake. Here, we attempted to evaluate the steroid effects on the liver and the blood pool uptake. A total of 38 CS patients who underwent FDG PET/CT before and during steroid therapy were retrospectively enrolled. Volumes of interest (VOIs) were placed in the right lobe of the liver and descending aorta (DA). The maximum standardized uptake value (SUVmax), SUVmean, and SUVpeak of the liver and DA were compared between time points before and during steroid therapy. RESULTS: The SUVmax, SUVmean, and SUVpeak of the liver during steroid therapy significantly increased from the time point before the therapy (SUVmax 3.5 ± 0.4 vs. 3.8 ± 0.6, p = 0.014; SUVmean 2.7 ± 0.3 vs. 3.0 ± 0.5, p = 0.0065; SUVpeak 3.0 ± 0.4 vs. 3.4 ± 0.6, p = 0.006). However, the SUVmax, SUVmean, and SUVpeak in the DA did not significantly change (SUVmax 2.2 ± 0.3 vs. 2.2 ± 0.4, p = 0.46; SUVmean 1.9 ± 0.3 vs. 2.0 ± 0.4, p = 0.56; SUVpeak 2.0 ± 0.3 vs. 2.0 ± 0.3, p = 0.70). CONCLUSIONS: We measured FDG uptake in the liver and blood pool before and during steroid therapy. Steroid therapy increased the liver uptake but not the blood pool uptake. Our findings suggested that the DA uptake is a more suitable threshold than liver uptake to evaluate therapeutic effects using volume-based analysis of cardiac FDG PET.
  • Masahiko Obara, Masanao Naya, Noriko Oyama-Manabe, Tadao Aikawa, Yuuki Tomiyama, Tsukasa Sasaki, Yasuka Kikuchi, Osamu Manabe, Chietsugu Katoh, Nagara Tamaki, Hiroyuki Tsutsui
    Medicine 97 (27) e11354  0025-7974 2018/07 [Refereed][Not invited]
     
    We have developed the method for dynamic 320-row multidetector computed tomography (MDCT)-derived quantitative coronary flow reserve (CFRCT) and hyperemic myocardial blood flow (MBFCT). We evaluated diagnostic value of CFRCT and hyperemic MBFCT for detecting obstructive coronary artery disease (CAD) in per-patient and per-vessel analysis, and their relations with the severity of CAD burden.Adenosine stressed and rest dynamic myocardial perfusion MDCT were prospectively performed in patients with known or suspected CAD. Per-patient and per-vessel MBFCT were estimated from dynamic perfusion images in rest and hyperemic phases, and per-patient and per-vessel CFRCT were calculated from the ratio of rest and hyperemic MBFCT. Degree of stenosis was evaluated by coronary CT angiography (CTA) and invasive coronary angiography (ICA). Obstructive stenosis was defined as ≥70% stenosis in ICA. CAD burden with MDCT was calculated by logarithm transformed coronary artery calcium (CAC) score and the CTA-adapted Leaman risk score (CT-LeSc). A logistic regression analysis was used to measure the receiver-operating characteristic curve and corresponding area under the curve (AUC) for the detection of obstructive CAD.Twenty-seven patients and 81 vessels were eligible for this study. Sixteen patients had obstructive CAD, and 31 vessels had obstructive stenosis. Using an optimal cutoff, the CFRCT and hyperemic MBFCT had the moderate diagnostic values in per-patient (AUC = 0.89 and 0.86, respectively) and per-vessel (AUC = 0.79 and 0.76, respectively). Per-patient CFRCT and hyperemic MBFCT exhibited a moderate inverse correlation with CAC score and the CT-LeSc.Per-patient and per-vessel CFRCT as well as hyperemic MBFCT had moderate diagnostic value for detecting obstructive CAD. These per-patient values exhibited a moderate inverse correlation with CAD burden. CFRCT and hyperemic MBFCT might add quantitative functional information for evaluating patients with CAD.
  • Tadao Aikawa, Atsuhito Takeda, Noriko Oyama-Manabe, Masanao Naya, Hirokuni Yamazawa, Kazuhiro Koyanagawa, Yoichi M. Ito, Yuka Ishikawa, Yukitoshi Ishikawa, Toshihisa Anzai
    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 71 (11) 1565 - 1565 0735-1097 2018/03 [Refereed][Not invited]
  • Keita Sakamoto, Noriko Oyama-Manabe, Osamu Manabe, Tadao Aikawa, Yasuka Kikuchi, Harue Sasai-Masuko, Masanao Naya, Kohsuke Kudo, Fumi Kato, Nagara Tamaki, Hiroki Shirato
    Japanese journal of radiology 36 (2) 103 - 112 1867-1071 2018/02 [Refereed][Not invited]
     
    PURPOSE: To evaluate heterogeneity of myocardial contraction in relation to extensive late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM) patients with preserved left ventricular ejection fraction, using fast strain-encoded magnetic resonance imaging. MATERIALS AND METHODS: Twenty-two HCM patients and 24 age-matched control subjects were included in this retrospective study. The regional and global peak values of longitudinal and circumferential strain (LSregional, LSglobal, CSregional, CSglobal), and their regional heterogeneities were evaluated using coefficients of variation (LSCoV, CSCoV) in relation to LGE. Receiver operating characteristic curve analysis was performed to identify patients with a total left ventricular myocardial LGE ≥ 15%. RESULTS: LSglobal in HCM patients was significantly decreased compared to that in controls (- 14.4 ± 2.4% vs - 17.2 ± 2.0%; p = 0.0004), while CSglobal was not (p = 1.0). Negative LGE segments demonstrated decreased LSregional in HCM patients compared to in controls (p < 0.0001), while CSregional was not decreased. CSCoV demonstrated the largest area under the curve (AUC) (0.91), with high sensitivity (83%) and specificity (94%) for detection of HCM patients with extensive LGE, while the AUC of LSCoV was low (0.49). CONCLUSION: The heterogeneity in CSregional has a high diagnostic value for detection of HCM patients with extensive LGE.
  • Yuji Hiroshima, Osamu Manabe, Masanao Naya, Yuuki Tomiyama, Keiichi Magota, Masahiko Obara, Tadao Aikawa, Noriko Oyama-Manabe, Keiichiro Yoshinaga, Kenji Hirata, Markus Kroenke, Nagara Tamaki, Chietsugu Katoh
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 1071-3581 2017/12/21 [Refereed][Not invited]
     
    BACKGROUND: 11C-hydroxyephedrine (HED) PET has been used to evaluate the myocardial sympathetic nervous system (SNS). Here we sought to establish a simultaneous approach for quantifying both myocardial blood flow (MBF) and the SNS from a single HED PET scan. METHODS: Ten controls and 13 patients with suspected cardiac disease were enrolled. The inflow rate of 11C-HED (K1) was obtained using a one-tissue-compartment model. We compared this rate with the MBF derived from 15O-H2O PET. In the controls, the relationship between K 1 from 11C-HED PET and the MBF from 15O-H2O PET was linked by the Renkin-Crone model. RESULTS: The relationship between K 1 from 11C-HED PET and the MBF from 15O-H2O PET from the controls' data was approximated as follows: K 1  =  (1 - 0.891 * exp(- 0.146/MBF)) * MBF. In the validation set, the correlation coefficient demonstrated a significantly high relationship for both the whole left ventricle (r = 0.95, P < 0.001) and three coronary territories (left anterior descending artery: r = 0.96, left circumflex artery: r = 0.81, right coronary artery: r =  0.86; P < 0.001, respectively). CONCLUSION: 11C-HED can simultaneously estimate MBF and sympathetic nervous function without requiring an additional MBF scan for assessing mismatch areas between MBF and SNS.
  • Osamu Manabe, Masanao Naya, Tadao Aikawa, Masahiko Obara, Keiichi Magota, Markus Kroenke, Noriko Oyama-Manabe, Kenji Hirata, Daiki Shinyama, Chietsugu Katoh, Nagara Tamaki
    EJNMMI research 7 (1) 52 - 52 2017/12 [Refereed][Not invited]
     
    BACKGROUND: The quantification of myocardial blood flow (MBF) and coronary flow reserve (CFR) are useful approaches for evaluating the functional severity of coronary artery disease (CAD). 15O-water positron emission tomography (PET) is considered the gold standard method for MBF quantification. However, MBF measurements in 15O-water PET with three-dimensional (3D) data acquisition, attenuation correction using computed tomography (CT), and time of flight have not been investigated in detail or validated. We conducted this study to evaluate the diagnostic potential of MBF measurements using PET/CT for a comparison of a control group and patients suspected of having CAD. RESULTS: Twenty-four patients with known or suspected CAD and eight age-matched healthy volunteers underwent rest and pharmacological stress perfusion studies with 15O-water PET/CT. The whole and three regional (left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) territory) MBF values were estimated. The CFR was computed as the ratio of the MBF during adenosine triphosphate-induced stress to the MBF at rest. The inter-observer variability was assessed by two independent observers. PET/CT using a 15O-water dose of 500 MBq and 3D data acquisition showed good image quality. A strong inter-observer correlation was detected in both the whole MBF analysis and the regional analysis with high intra-class correlation coefficients (r > 0.90, p < 0.001). Regional MBF at rest (LAD, 0.82 ± 0.15 ml/min/g; LCX, 0.83 ± 0.17 ml/min/g; RCA, 0.71 ± 0.20 ml/min/g; p = 0.74), MBF at stress (LAD, 3.77 ± 1.00 ml/min/g; LCX, 3.56 ± 1.01 ml/min/g; RCA, 3.27 ± 1.04 ml/min/g; p = 0.62), and CFR (LAD, 4.64 ± 0.90; LCX, 4.30 ± 0.64; RCA, 4.64 ± 0.96; p = 0.66) of the healthy volunteers showed no significant difference among the three regions. The global CFR of the patients was significantly lower than that of the volunteers (2.75 ± 0.81 vs. 4.54 ± 0.66, p = 0.0002). The regional analysis of the patients demonstrated that the CFR tended to be lower in the stenotic region compared to the non-stenotic region (2.43 ± 0.81 vs. 2.95 ± 0.92, p = 0.052). CONCLUSIONS: 15O-water PET/CT with 3D data acquisition can be reliably used for the quantification of functional MBF and CFR in CAD patients.
  • Tadao Aikawa, Noriko Oyama-Manabe, Masanao Naya, Hiroshi Ohira, Ayako Sugimoto, Ichizo Tsujino, Masahiko Obara, Osamu Manabe, Kohsuke Kudo, Hiroyuki Tsutsui, Nagara Tamaki
    European radiology 27 (10) 4054 - 4063 0938-7994 2017/10 [Refereed][Not invited]
     
    OBJECTIVES: To evaluate the diagnostic value of delayed contrast-enhanced computed tomography (DE-CT) for cardiac sarcoidosis (CS) in patients with or without implantable devices, including a quantitative comparison with late gadolinium enhancement cardiac magnetic resonance (LGE-CMR). METHODS: Twenty-four patients (mean age, 64 ± 9 years; 17 women) with known or suspected CS underwent retrospective electrocardiogram-gated DE-CT at 80 kV with knowledge-based iterative model reconstruction. Fourteen patients without implantable devices also underwent LGE-CMR, while ten with pacemakers or implantable cardioverter-defibrillators did not. The presence of hyperenhanced myocardium was assessed visually and quantitatively using a 5-standard deviation threshold above the mean of remote myocardium. RESULTS: Inter-observer agreement for visual detection of hyperenhanced segments on DE-CT was excellent in patients with implantable devices and in those without (κ = 0.91 and κ = 0.94, respectively). Comparisons of the percent area of hyperenhanced myocardium between DE-CT and LGE-CMR on both per-patient and per-segment analyses showed good correlations (r = 0.96 and r = 0.83, respectively; p < 0.001). The sensitivity and specificity of DE-CT for the diagnosis of CS were 94% and 33%. CONCLUSIONS: The extent of hyperenhanced lesion with DE-CT showed good agreement with LGE-CMR results. DE-CT showed high sensitivity for detecting CS and may be useful particularly in patients with contraindications to CMR. KEY POINTS: • Delayed contrast-enhanced CT (DE-CT) can be applied to patients with implantable devices. • DE-CT can detect cardiac sarcoidosis (CS) lesions similarly to cardiac MRI. • DE-CT shows high sensitivity for detecting CS. • DE-CT may be useful particularly in patients with contraindications to cardiac MRI.
  • Tadao Aikawa, Masanao Naya, Masahiko Obara, Noriko Oyama-Manabe, Osamu Manabe, Keiichi Magota, Yoichi M Ito, Chietsugu Katoh, Nagara Tamaki
    European journal of nuclear medicine and molecular imaging 44 (11) 1897 - 1905 1619-7070 2017/10 [Refereed][Not invited]
     
    PURPOSE: This investigation aimed to identify significant predictors of regional sympathetic denervation quantified by 11C-hydroxyephedrine (HED) positron emission tomography (PET) in patients with heart failure with preserved left ventricular ejection fraction (HFpEF). METHODS: Included in the study were 34 patients (age 63 ± 15 years, 23 men) with HFpEF (left ventricular ejection fraction ≥40%) and 11 age-matched volunteers without heart failure. Cardiac magnetic resonance imaging was performed to measure left ventricular size and function, and the extent of myocardial late gadolinium enhancement (LGE). 11C-HED PET was performed to quantify myocardial sympathetic innervation that was expressed as a 11C-HED retention index (RI, %/min). To identify predictors of regional 11C-HED RI in HFpEF patients, we propose a multivariate mixed-effects model for repeated measures over segments with an unstructured covariance matrix. RESULTS: Global 11C-HED RI was significantly lower and more heterogeneous in HFpEF patients than in volunteers (P < 0.01 for all). Regional 11C-HED RI was correlated positively with systolic wall thickening (r = 0.42, P < 0.001) and negatively with the extent of LGE (r = -0.43, P < 0.001). Segments in HFpEF patients with a large extent of LGE had the lowest regional 11C-HED RI among all segments (P < 0.001 in post hoc tests). Multivariate analysis demonstrated that systolic wall thickening and the extent of LGE were significant predictors of regional 11C-HED RI in HFpEF patients (both P ≤ 0.001). CONCLUSION: Regional sympathetic denervation was associated with contractile dysfunction and fibrotic burden in HFpEF patients, suggesting that regional sympathetic denervation may provide an integrated measure of myocardial damage in HFpEF.
  • 左室収縮が保持された心不全における11C-HED PETを用いた局所心筋交感神経分布の検討
    相川 忠夫, 納谷 昌直, 小原 雅彦, 真鍋 徳子, 真鍋 治, 小梁川 和宏, 孫田 恵一, 伊藤 陽一, 志賀 哲, 加藤 千恵次, 玉木 長良
    核医学 (一社)日本核医学会 54 (Suppl.) S174 - S174 0022-7854 2017/09 [Refereed][Not invited]
  • 心サルコイドーシスにおけるFDG集積定量評価の再現性
    真鍋 治, 平田 健司, 大平 洋, 納谷 昌直, 相川 忠夫, 真鍋 徳子, 志賀 哲
    核医学 (一社)日本核医学会 54 (Suppl.) S174 - S174 0022-7854 2017/09 [Refereed][Not invited]
  • Osamu Manabe, Masanao Naya, Nagara Tamaki
    Journal of cardiology 70 (2) 135 - 140 0914-5087 2017/08 [Refereed][Not invited]
     
    Myocardial perfusion imaging using positron emission tomography (PET) allows both qualitative and quantitative measurement. The quantitative myocardial blood flow and coronary flow reserve (CFR) are reliable indices for evaluating functional severity, influenced by both epicardial stenosis and microvascular disease. Fractional flow reserve (FFR) also reflects physiological stenosis, which measures the pressure differences across a coronary artery stenosis during maximum hyperemia. Discordance between CFR and FFR has been noticed in estimating the functional significance of coronary stenosis. In this review, we summarize the feasibility of PET for the management of coronary artery disease compared to FFR.
  • Tadao Aikawa, Masanao Naya, Noriko Oyama-Manabe, Satoshi Maekawa, Hideo Nambu, Hirofumi Mitsuyama, Kenji Hirata, Hiromi Kanno-Okada, Hiroyuki Tsutsui
    JOURNAL OF NUCLEAR CARDIOLOGY 24 (3) 1107 - 1109 1071-3581 2017/06 [Refereed][Not invited]
  • Osamu Manabe, Noriko Oyama-Manabe, Masanao Naya, Tadao Aikawa, Mamoru Sakakibara, Hiroyuki Tsutsui, Nagara Tamaki
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 24 (3) 1110 - 1113 1071-3581 2017/06 [Refereed][Not invited]
  • Tadao Aikawa, Masanao Naya, Masahiko Obara, Osamu Manabe, Yuuki Tomiyama, Keiichi Magota, Satoshi Yamada, Chietsugu Katoh, Nagara Tamaki, Hiroyuki Tsutsui
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine 58 (5) 784 - 790 0161-5505 2017/05 [Refereed][Not invited]
     
    Diastolic dysfunction is important in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). Sympathetic nervous hyperactivity may contribute to the development of diastolic dysfunction. The aim of this study was to determine the relationship between myocardial sympathetic innervation quantified by 11C-hydroxyephedrine PET and diastolic dysfunction in HFpEF patients. Methods: Forty-one HFpEF patients having an echocardiographic left ventricular ejection fraction of 40% or greater and 12 age-matched volunteers without heart failure underwent the echocardiographic examination and 11C-hydroxyephedrine PET. Diastolic dysfunction was classified into grades 0-3 by Doppler echocardiography. Myocardial sympathetic innervation was quantified using the 11C-hydroxyephedrine retention index (RI). The coefficient of variation of 17-segment RIs was derived as a measure of heterogeneity in myocardial 11C-hydroxyephedrine uptake. Results: Grade 2-3 diastolic dysfunction (DD2-3) was found in 19 HFpEF patients (46%). They had a significantly lower global RI (0.075 ± 0.018 min-1) than volunteers (0.123 ± 0.028 min-1, P < 0.001) and HFpEF patients with grade 0-1 diastolic dysfunction (DD0-1) (0.092 ± 0.024 min-1, P = 0.046). HFpEF patients with DD2-3 had the largest coefficient of variation of 17-segment RIs of the 3 groups (18.4% ± 7.7% vs. 14.1% ± 4.7% in HFpEF patients with DD0-1, P = 0.042 for post hoc tests). In multivariate logistic regression analysis, a lower global RI (odds ratio, 0.66 per 0.01 min-1; 95% confidence interval, 0.38-0.99; P = 0.044) was independently associated with the presence of DD2-3 in HFpEF patients. Conclusion: Myocardial sympathetic innervation was impaired in HFpEF patients and was associated with the presence of advanced diastolic dysfunction in HFpEF.
  • Atsuro Masuda, Osamu Manabe, Noriko Oyama-Manabe, Masanao Naya, Masahiko Obara, Mamoru Sakakibara, Kenji Hirata, Satoshi Yamada, Tomoaki Naka, Hiroyuki Tsutsui, Nagara Tamaki
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 24 (1) 323 - 324 1071-3581 2017/02 [Refereed][Not invited]
  • Atsuro Masuda, Keiichiro Yoshinaga, Masanao Naya, Osamu Manabe, Satoshi Yamada, Hiroyuki Iwano, Tatsuya Okada, Chietsugu Katoh, Yasuchika Takeishi, Hiroyuki Tsutsui, Nagara Tamaki
    EJNMMI research 6 (1) 41 - 41 2016/12 [Refereed][Not invited]
     
    BACKGROUND: Accelerated clearance of (99m)technetium-sestamibi (MIBI) has been observed after reperfusion therapy in patients with acute coronary syndrome (ACS), but the mechanisms have not been fully investigated. MIBI retention may depend on mitochondrial function. The clearance rate of (11)carbon-acetate reflects such mitochondrial functions as oxidative metabolism. The purpose of this study was to examine the mechanisms of accelerated MIBI clearance in ACS. We therefore compared it to oxidative metabolism estimated using (11)C-acetate positron emission tomography (PET). METHODS: Eighteen patients [mean age 69.2 ± 8.7 years, 10 males (56 %)] with reperfused ACS underwent MIBI single-photon emission computed tomography (SPECT), echocardiography, and (11)C-acetate PET within 3 weeks of the onset of ACS. MIBI images were obtained 30 min and 3 h after MIBI administration. Regional left ventricular (LV) function was evaluated by echocardiography. The measurement of oxidative metabolism was obtained through the mono-exponential fitting of the (11)C-acetate time-activity curve (k mono). RESULTS: Among 95 segments of reperfused myocardium, MIBI SPECT showed 64 normal segments (group N), 14 segments with accelerated MIBI clearance (group AC), and 17 segments with fixed defect (group F). Group AC showed lower k mono than group N (0.041 ± 0.009 vs 0.049 ± 0.010, p = 0.02). Group F showed lower k mono than group N (0.039 ± 0.012 vs 0.049 ± 0.010, p = 0.01). However, k mono was similar in group AC and group F (p = 0.99). CONCLUSIONS: Segments with accelerated MIBI clearance showed reduced oxidative metabolism in ACS. Loss of MIBI retention may be associated with mitochondrial dysfunction.
  • 15O-H2O心筋血流PETにおける撮像時間短縮の検討:新アルゴリズムの考案
    林 蒼一朗, 富山 勇輝, 相川 忠夫, 真鍋 治, 納谷 昌直, 小原 雅彦, 孫田 惠一, 吉永 恵一郎, 丸尾 彩花, 加藤 千恵次, 玉木 長良
    核医学 (一社)日本核医学会 53 (Suppl.) S261 - S261 0022-7854 2016/10 [Refereed][Not invited]
  • 15O-H2O心筋血流PETにおける撮像時間短縮の検討:局所病変検出能の評価
    川内 敬介, 富山 勇輝, 相川 忠夫, 真鍋 治, 納谷 昌直, 小原 雅彦, 孫田 惠一, 吉永 恵一郎, 丸尾 彩花, 加藤 千恵次, 玉木 長良
    核医学 (一社)日本核医学会 53 (Suppl.) S261 - S261 0022-7854 2016/10 [Refereed][Not invited]
  • Tadao Aikawa, Masanao Naya, Osamu Manabe, Masahiko Obara, Shouji Matsushima, Nagara Tamaki, Hiroyuki Tsutsui
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 23 (3) 596 - 8 1071-3581 2016/06 [Refereed][Not invited]
  • Atsuro Masuda, Masanao Naya, Osamu Manabe, Keiichi Magota, Keiichiro Yoshinaga, Hiroyuki Tsutsui, Nagara Tamaki
    Acta radiologica (Stockholm, Sweden : 1987) 57 (6) 661 - 8 0284-1851 2016/06 [Refereed][Not invited]
     
    BACKGROUND: The physiological uptake of 18F-fluorodeoxyglucose (FDG) in the heart often interferes with the accurate diagnosis of inflammatory cardiac diseases (CDs). Unfractionated heparin (UFH) administration may suppress its uptake through the alteration of myocardial metabolism. PURPOSE: To clarify the effectiveness of UFH administration to suppress the physiological FDG uptake in the heart. MATERIAL AND METHODS: The physiological FDG uptake in the heart was compared among 178 patients who fasted less than 18 h, 37 patients who fasted more than 18 h, and 64 patients who fasted more than 18 h and were administered UFH (UFH-CD group) prior to FDG PET/CT. Free fatty acid (FFA), triglyceride, insulin, and blood glucose levels were measured after UFH administration. Myocardial FDG uptake was evaluated by visual assessment and on the basis of maximum standardized uptake value (SUVmax). RESULTS: In the UFH-CD group, the FFA level increased 15 min after UFH administration (P < 0.01). Blood glucose and insulin levels remained unchanged (P = NS). FDG physiological uptake was observed in 69% of the patients who fasted less than 18 h, 38% of the patients fasted more than 18 h, and 22% of the UFH-CD group (P < 0.01 for trend). SUVmax decreased in the UFH-CD group compared with the patients who fasted less than 18 h (P < 0.01) and the patients who fasted more than 18 h (P = 0.029). CONCLUSION: UFH administration and fasting more than 18 h could effectively suppress FDG physiological uptake in the heart and can be a useful method of detecting inflammatory CDs and tumors.
  • Masanao Naya, Nagara Tamaki
    JOURNAL OF NUCLEAR CARDIOLOGY 23 (2) 198 - 201 1071-3581 2016/04 [Refereed][Not invited]
  • Yuuki Tomiyama, Osamu Manabe, Noriko Oyama-Manabe, Masanao Naya, Hiroyuki Sugimori, Kenji Hirata, Yuki Mori, Hiroyuki Tsutsui, Kohsuke Kudo, Nagara Tamaki, Chietsugu Katoh
    Journal of magnetic resonance imaging : JMRI 42 (3) 754 - 62 1053-1807 2015/09 [Refereed][Not invited]
     
    BACKGROUND: To develop and validate a method for quantifying myocardial blood flow (MBF) using dynamic perfusion magnetic resonance imaging (MBFMRI ) at 3.0 Tesla (T) and compare the findings with those of (15) O-water positron emission tomography (MBFPET ). METHODS: Twenty healthy male volunteers underwent magnetic resonance imaging (MRI) and (15) O-water positron emission tomography (PET) at rest and during adenosine triphosphate infusion. The single-tissue compartment model was used to estimate the inflow rate constant (K1). We estimated the extraction fraction of Gd-DTPA using K1 and MBF values obtained from (15) O-water PET for the first 10 subjects. For validation, we calculated MBFMRI values for the remaining 10 subjects and compared them with the MBFPET values. In addition, we compared MBFMRI values of 10 patients with coronary artery disease with those of healthy subjects. RESULTS: The mean resting and stress MBFMRI values were 0.76 ± 0.10 and 3.04 ± 0.82 mL/min/g, respectively, and showed excellent correlation with the mean MBFPET values (r = 0.96, P < 0.01). The mean stress MBFMRI value was significantly lower for the patients (1.92 ± 0.37) than for the healthy subjects (P < 0.001). CONCLUSION: The use of dynamic perfusion MRI at 3T is useful for estimating MBF and can be applied for patients with coronary artery disease.
  • Masanao Naya, Hiroyuki Tsutsui
    CIRCULATION JOURNAL 79 (3) 515 - 516 1346-9843 2015/03 [Refereed][Not invited]
  • Murthy VL, Naya M, Taqueti VR, Foster CR, Gaber M, Hainer J, Dorbala S, Blankstein R, Rimoldi O, Camici PG, Di Carli MF
    Circulation 131 (11) e376  0009-7322 2015/03 [Refereed][Not invited]
  • Yuki Mori, Osamu Manabe, Masanao Naya, Yuuki Tomiyama, Keiichiro Yoshinaga, Keiichi Magota, Noriko Oyama-Manabe, Kenji Hirata, Hiroyuki Tsutsui, Nagara Tamaki, Chietsugu Katoh
    Annals of nuclear medicine 29 (1) 15 - 20 0914-7187 2015/01 [Refereed][Not invited]
     
    OBJECTIVE: (11)C-acetate has been applied for evaluation of myocardial oxidative metabolism and can simultaneously estimate myocardial blood flow (MBF). We developed a new method using two-parameter spillover correction to estimate regional MBF (rMBF) with (11)C-acetate PET in reference to MBF derived from (15)O-H2O PET. The usefulness of our new approach was evaluated compared to the conventional method using one-parameter spillover correction. METHODS: Sixty-three subjects were examined with (11)C-acetate and (15)O-H2O dynamic PET at rest. Inflow rate of (11)C-acetate (K1) was compared with MBF derived from (15)O-H2O PET. For the derivation, the relationship between K1 and MBF from (15)O-H2O was linked by the Renkin-Crone model in 20 subjects as a pilot group. One-parameter and two-parameter corrections were applied to suppress the spillover between left ventricular (LV) wall and LV cavity. Validation was set using the other 43 subjects' data. Finally, rMBFs were calculated using relational expression derived from the pilot-group data. RESULTS: The relationship between K1 and MBF derived from (15)O-H2O PET was approximated as K1 = [1-0.764 × exp(-1.001/MBF)] MBF from the pilot data using the two-parameter method. In the validation set, the correlation coefficient between rMBF from (11)C-acetate and (15)O-H2O demonstrated a significantly higher relationship with the two-parameter spillover correction method than the one-parameter spillover correction method (r = 0.730, 0.592, respectively, p < 0.05). CONCLUSION: In (11)C-acetate PET study, the new two-parameter spillover correction method dedicated more accurate and robust myocardial blood flow than the conventional one-parameter method.
  • Viviany R. Taqueti, Rory Hachamovitch, Venkatesh L. Murthy, Masanao Naya, Courtney R. Foster, Jon Hainer, Sharmila Dorbala, Ron Blankstein, Marcelo F. Di Carli
    CIRCULATION 131 (1) 19 - + 0009-7322 2015/01 [Refereed][Not invited]
     
    Background-Coronary flow reserve (CFR), an integrated measure of focal, diffuse, and small-vessel coronary artery disease (CAD), identifies patients at risk for cardiac death . We sought to determine the association between CFR, angiographic CAD, and cardiovascular outcomes . Methods and Results-Consecutive patients (n=329) referred for invasive coronary angiography after stress testing with myocardial perfusion positron emission tomography were followed (median 3 .1 years) for cardiovascular death and heart failure admission . The extent and severity of angiographic disease were estimated with the use of the CAD prognostic index, and CFR was measured noninvasively by positron emission tomography . A modest inverse correlation was seen between CFR and CAD prognostic index (r=-0.26; P<0.0001). After adjustment for clinical risk score, ejection fraction, global ischemia, and early revascularization, CFR and CAD prognostic index were independently associated with events (hazard ratio for unit decrease in CFR, 2.02; 95% confidence interval, 1.20-3.40; P=0.008; hazard ratio for 10-U increase in CAD prognostic index, 1.17; 95% confidence interval, 1.01-1.34; P=0.032). Subjects with low CFR experienced rates of events similar to those of subjects with high angiographic scores, and those with low CFR or high CAD prognostic index showed the highest risk of events (P=0.001). There was a significant interaction (P=0.039) between CFR and early revascularization by coronary artery bypass grafting, such that patients with low CFR who underwent coronary artery bypass grafting, but not percutaneous coronary intervention, experienced event rates comparable to those with preserved CFR, independently of revascularization . Conclusions-CFR was associated with outcomes independently of angiographic CAD and modified the effect of early revascularization . Diffuse atherosclerosis and associated microvascular dysfunction may contribute to the pathophysiology of cardiovascular death and heart failure, and impact the outcomes of revascularization .
  • Masanao Naya, Nagara Tamaki, Hiroyuki Tsutsui
    CIRCULATION JOURNAL 79 (1) 15 - 23 1346-9843 2015/01 [Refereed][Not invited]
     
    Coronary artery disease (CAD) is a major cause of death in Japan. Coronary angiography is useful to assess the atherosclerotic burden in CAD patients, but its ability to predict whether patients will respond favorably to optimal medical therapy and revascularization is limited. The measurement of the fractional flow reserve with angiography is a well-validated method for identifying ischemic vessels. However, neither an anatomical assessment nor a functional assessment can delineate microvasculature or estimate its function. The quantitative coronary flow reserve (CFR) estimated from sequential myocardial perfusion images obtained by positron emission tomography (PET) during stress provides an accurate index of hyperemic reactivity to vasodilatory agents in the myocardium. In fact, there is growing evidence that the CFR reflects disease activity in the entire coronary circulation, including epicardial coronary artery stenosis, diffuse atherosclerosis, and microvascular dilatory function. Importantly, reduced CFR is observed even in patients without flow-limiting coronary stenosis, and its evaluation can improve the risk stratification of patients at any stage of CAD. This review focuses on the application of CFR estimated by cardiac PET for the diagnosis and risk stratification of patients with CAD.
  • Venkatesh L. Murthy, Benjamin C. Lee, Arkadiusz Sitek, Masanao Naya, Jonathan Moody, Vivek Polavarapu, Edward P. Ficaro, Marcelo F. Di Carli
    JOURNAL OF NUCLEAR MEDICINE 55 (12) 1952 - 1958 0161-5505 2014/12 [Refereed][Not invited]
     
    The quantification of myocardial blood flow (MBF) and myocardial flow reserve (MFR) using PET with Rb-82 in patients with known or suspected coronary artery disease has been demonstrated to have substantial prognostic and diagnostic value. However, multiple methods for estimation of an image-derived input function and several models for the nonlinear first-pass extraction of Rb-82 by myocardium have been used. We sought to compare the differences in these methods and models and their impact on prognostic assessment in a large clinical dataset. Methods: Consecutive patients (n = 2,783) underwent clinically indicated rest-stress myocardial perfusion PET with Rb-82. The input function was derived using a region of interest (ROI) semiautomatically placed in the region of the mitral valve, factor analysis, and a hybrid method that creates an ROI from factor analysis. We used 5 commonly used extraction models for Rb-82 to estimate MBF and MFR. Pearson correlations, bias, and Cohen. were computed for the various measures. The relationship between MFR/stress MBF and annual rate of cardiac mortality was estimated with spline fits using Poisson regression. Finally, incremental value was assessed with the net reclassification improvement using Cox proportional hazards regression. Results: Correlations between MFR or stress MBF measures made with the same input function derivation method were generally high, regardless of extraction model used (Pearson r > 0.90). However, correlations between measures derived with the ROI method and other methods were only moderate (Pearson r = 0.42-0.62). Importantly, substantial biases were seen for most combinations. We saw that the relationship between cardiac mortality and stress MBF was variable depending on the input function method and extraction model, whereas the relationship between MFR and risk was highly consistent. Net reclassification improvement was comparable for most methods and models for MFR but was highly variable for stress MBF. Conclusion: Although both stress MBF and MFR can improve prognostic assessment, MFR is substantially more consistent, regardless of choice of input function derivation method and extraction model used.
  • Yasuka Kikuchi, Noriko Oyama-Manabe, Masanao Naya, Osamu Manabe, Yuuki Tomiyama, Tsukasa Sasaki, Chietsugu Katoh, Kohsuke Kudo, Nagara Tamaki, Hiroki Shirato
    European radiology 24 (7) 1547 - 56 0938-7994 2014/07 [Refereed][Not invited]
     
    OBJECTIVES: This study introduces a method to calculate myocardium blood flow (MBF) and coronary flow reserve (CFR) using the relatively low-dose dynamic 320-row multi-detector computed tomography (MDCT), validates the method against (15)O-H₂O positron-emission tomography (PET) and assesses the CFRs of coronary artery disease (CAD) patients. METHODS: Thirty-two subjects underwent both dynamic CT perfusion (CTP) and PET perfusion imaging at rest and during pharmacological stress. In 12 normal subjects (pilot group), the calculation method for MBF and CFR was established. In the other 13 normal subjects (validation group), MBF and CFR obtained by dynamic CTP and PET were compared. Finally, the CFRs obtained by dynamic CTP and PET were compared between the validation group and CAD patients (n = 7). RESULTS: Correlation between MBF of MDCT and PET was strong (r = 0.95, P < 0.0001). CFR showed good correlation between dynamic CTP and PET (r = 0.67, P = 0.0126). CFRCT in the CAD group (2.3 ± 0.8) was significantly lower than that in the validation group (5.2 ± 1.8) (P = 0.0011). CONCLUSIONS: We established a method for measuring MBF and CFR with the relatively low-dose dynamic MDCT. Lower CFR was well demonstrated in CAD patients by dynamic CTP. KEY POINTS: • MBF and CFR can be calculated using dynamic CTP with 320-row MDCT. • MBF and CFR showed good correlation between dynamic CTP and PET. • Lower CFR was well demonstrated in CAD patients by dynamic CTP.
  • Venkatesh L. Murthy, Masanao Naya, Viviany R. Taqueti, Courtney R. Foster, Mariya Gaber, Jon Hainer, Sharmila Dorbala, Ron Blankstein, Ornella Rimoldi, Paolo G. Camici, Marcelo F. Di Carli
    CIRCULATION 129 (24) 2518 - 2527 0009-7322 2014/06 [Refereed][Not invited]
     
    Background Coronary microvascular dysfunction (CMD) is a prevalent and prognostically important finding in patients with symptoms suggestive of coronary artery disease. The relative extent to which CMD affects both sexes is largely unknown. Methods and Results We investigated 405 men and 813 women who were referred for evaluation of suspected coronary artery disease with no previous history of coronary artery disease and no visual evidence of coronary artery disease on rest/stress positron emission tomography myocardial perfusion imaging. Coronary flow reserve was quantified, and coronary flow reserve <2.0 was used to define the presence of CMD. Major adverse cardiac events, including cardiac death, nonfatal myocardial infarction, late revascularization, and hospitalization for heart failure, were assessed in a blinded fashion over a median follow-up of 1.3 years (interquartile range, 0.5-2.3 years). CMD was highly prevalent both in men and women (51% and 54%, respectively; Fisher exact test =0.39; equivalence P=0.0002). Regardless of sex, coronary flow reserve was a powerful incremental predictor of major adverse cardiac events (hazard ratio, 0.80 [95% confidence interval, 0.75-086] per 10% increase in coronary flow reserve; P<0.0001) and resulted in favorable net reclassification improvement (0.280 [95% confidence interval, 0.049-0.512]), after adjustment for clinical risk and ventricular function. In a subgroup (n=404; 307 women/97 men) without evidence of coronary artery calcification on gated computed tomography imaging, CMD was common in both sexes, despite normal stress perfusion imaging and no coronary artery calcification (44% of men versus 48% of women; Fisher exact test P=0.56; equivalence P=0.041). Conclusions CMD is highly prevalent among at-risk individuals and is associated with adverse outcomes regardless of sex. The high prevalence of CMD in both sexes suggests that it may be a useful target for future therapeutic interventions.
  • Keiichi Magota, Naoya Hattori, Osamu Manabe, Masanao Naya, Noriko Oyama-Manabe, Tohru Shiga, Yuji Kuge, Shiro Yamada, Mamoru Sakakibara, Keiichiro Yoshinaga, Nagara Tamaki
    Annals of nuclear medicine 28 (3) 187 - 95 0914-7187 2014/04 [Refereed][Not invited]
     
    OBJECTIVE: Application of the electrocardiographically (ECG) gated positron emission tomography (PET) technique with (11)C-hydroxyephedrine (HED) would allow the simultaneous assessment of cardiac sympathetic and contractile functions. However, there are uncertainties regarding the diagnostic accuracy of left ventricular (LV) volume measurements using ECG-gated HED-PET. The purpose of this study was to clarify the minimal requirement of count statistics to measure LV volumes with ECG-gated HED-PET and to investigate the reliability of the measurements. METHODS: Five healthy volunteers and 11 patients with heart failure underwent a 40-min list-mode PET scan after an injection of HED (197 ± 35 MBq). The list-mode data were histogrammed into multiple sets of acquisition periods at 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 12.0 Mcount/bin and reconstructed into corresponding gated images using an iterative algorithm. The LV end-diastolic volume (LVEDV), the LV end-systolic volume (LVESV), and the LV ejection fraction (LVEF) were calculated in each acquisition period. These values were compared with those obtained by cardiac magnetic resonance imaging (MRI). Possible effects of HED retention on the accuracy of the volume measurements were investigated. RESULTS: Collecting less than 4.0 Mcount/bin resulted in noisy cardiac images. The lower counts resulted in underestimation in the volume measurements. Reasonably accurate volume measurements required equal to or greater than 6.0 Mcount/bin. This corresponded to 7.0 ± 1.9 min (range, 4.0-10.3 min) for the acquisition period. Volumetric results using the 6.0 Mcount/bin data highly correlated with cardiac MRI (LVEDV: r = 0.85, p < 0.0001; LVESV: r = 0.89, p < 0.0001; LVEF: r = 0.77, p < 0.01). The HED retention did not affect the volumetric results compared to the MRI volumetry. CONCLUSIONS: The volumetric accuracy with ECG-gated HED-PET was affected by the count statistics rather than the HED retention. LV volume measurements were feasible with 10-min acquisition period for most of the patients. This technique allows the simultaneous assessment of cardiac sympathetic and contractile functions without the need for an additional injection or scanning time, thus reducing overall costs for diagnostic imaging.
  • Ron Blankstein, Michael Osborne, Masanao Naya, Alfonso Waller, Chun K. Kim, Venkatesh L. Murthy, Pedram Kazemian, Raymond Y. Kwong, Michifumi Tokuda, Hicham Skali, Robert Padera, Jon Hainer, William G. Stevenson, Sharmila Dorbala, Marcelo F. Di Carli
    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 63 (4) 329 - 336 0735-1097 2014/02 [Refereed][Not invited]
     
    Objectives This study sought to relate imaging findings on positron emission tomography (PET) to adverse cardiac events in patients referred for evaluation of known or suspected cardiac sarcoidosis. Background Although cardiac PET is commonly used to evaluate patients with suspected cardiac sarcoidosis, the relationship between PET findings and clinical outcomes has not been reported. Methods We studied 118 consecutive patients with no history of coronary artery disease, who were referred for PET, using [F-18]fluorodeoxyglucose (FDG) to assess for inflammation and rubidium-82 to evaluate for perfusion defects (PD), following a high-fat/low-carbohydrate diet to suppress normal myocardial glucose uptake. Blind readings of PET data categorized cardiac findings as normal, positive PD or FDG, positive PD and FDG. Images were also used to identify whether findings of extra-cardiac sarcoidosis were present. Adverse events (AE)-death or sustained ventricular tachycardia (VT)-were ascertained by electronic medical records, defibrillator interrogation, patient questionnaires, and telephone interviews. Results Among the 118 patients (age 52 +/- 11 years; 57% males; mean ejection fraction: 47 +/- 16%), 47 (40%) had normal and 71 (60%) had abnormal cardiac PET findings. Over a median follow-up of 1.5 years, there were 31 (26%) adverse events (27 VT and 8 deaths). Cardiac PET findings were predictive of AE, and the presence of both a PD and abnormal FDG (29% of patients) was associated with hazard ratio of 3.9 (p < 0.01) and remained significant after adjusting for left ventricular ejection fraction (LVEF) and clinical criteria. Extra-cardiac FDG uptake (26% of patients) was not associated with AE. Conclusions The presence of focal PD and FDG uptake on cardiac PET identifies patients at higher risk of death or VT. These findings offer prognostic value beyond Japanese Ministry of Health and Welfare clinical criteria, the presence of extra-cardiac sarcoidosis and LVEF. (C) 2014 by the American College of Cardiology Foundation
  • Keiichiro Yoshinaga, Masanao Naya, Tohru Shiga, Eriko Suzuki, Nagara Tamaki
    EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 41 (2) 384 - 393 1619-7070 2014/02 [Refereed][Not invited]
     
    "Ischaemic memory" is defined as a prolonged functional and/or biochemical alteration remaining after a particular episode of severe myocardial ischaemia. The biochemical alteration has been reported as metabolic stunning. Metabolic imaging has been used to detect the footprint left by previous ischaemic episodes evident due to delayed recovery of myocardial metabolism (persistent dominant glucose utilization with suppression of fatty acid oxidation). beta-Methyl-p-[I-123]iodophenylpentadecanoic acid (BMIPP) is a single-photon emission computed tomography (SPECT) radiotracer widely used for metabolic imaging in clinical settings in Japan. In patients with suspected coronary artery disease but no previous myocardial infarction, BMIPP has shown acceptable diagnostic accuracy. In particular, BMIPP plays an important role in the identification of prior ischaemic insult in patients arriving at emergency departments with acute chest pain syndrome. Recent data also show the usefulness of I-123-BMIPP SPECT for predicting cardiovascular events in patients undergoing haemodialysis. Similarly, SPECT or PET imaging with F-18-FDG injected during peak exercise or after exercise under fasting conditions shows an increase in FDG uptake in postischaemic areas. This article will overview the roles of ischaemic memory imaging both under established indications and in ongoing investigations.
  • Masanao Naya, Venkatesh L. Murthy, Viviany R. Taqueti, Courtney R. Foster, Josh Klein, Mariya Garber, Sharmila Dorbala, Jon Hainer, Ron Blankstein, Frederick Resnic, Marcelo F. Di Carli
    JOURNAL OF NUCLEAR MEDICINE 55 (2) 248 - 255 0161-5505 2014/02 [Refereed][Not invited]
     
    Myocardial perfusion imaging has limited sensitivity for the detection of high-risk coronary artery disease (CAD). We tested the hypothesis that a normal coronary flow reserve (CFR) would be helpful for excluding the presence of high-risk CAD on angiography. Methods: We studied 290 consecutive patients undergoing Rb-82 PET within 180 d of invasive coronary angiography. High-risk CAD on angiography was defined as 2-vessel disease (>= 70% stenosis), including the proximal left anterior descending artery; 3-vessel disease; or left main CAD (>= 50% stenosis). Patients with prior Q wave myocardial infarction, elevated troponin levels between studies, prior coronary artery bypass grafting, a left ventricular ejection fraction of less than 40%, or severe valvular heart disease were excluded. Results: Fifty-five patients (19%) had high-risk CAD on angiography. As expected, the trade-off between the sensitivity and the specificity of the CFR for identifying high-risk CAD varied substantially depending on the cutoff selected. In multivariable analysis, a binary CFR of less than or equal to 1.93 provided incremental diagnostic information for the identification of high-risk CAD beyond the model with the Duke clinical risk score (>25%), percentage of left ventricular ischemia (>10%), transient ischemic dilation index (>1.07), and change in the left ventricular ejection fraction during stress (<2) (P = 0.0009). In patients with normal or slightly to moderately abnormal results on perfusion scans (<10% of left ventricular mass) during stress (n = 136), a preserved CFR (>1.93) excluded high-risk CAD with a high sensitivity (86%) and a high negative predictive value (97%). Conclusion: A normal CFR has a high negative predictive value for excluding high-risk CAD on angiography. Although an abnormal CFR increases the probability of significant obstructive CAD, it cannot reliably distinguish significant epicardial stenosis from nonobstructive, diffuse atherosclerosis or microvascular dysfunction.
  • Naya M, Tamaki N
    Current cardiovascular imaging reports 7 9244  1941-9066 2014 [Refereed][Not invited]
  • Cardiac magnetic resonance performs better in the detection of functionally significant coronary artery stenosis compared to single-photon emission computed tomography and dobutamine stress echocardiography.
    Kiwamu Kamiya, Mamoru Sakakibara, Naoya Asakawa, Shiro Yamada, Takashi Yoshitani, Hiroyuki Iwano, Hiroshi Komatsu, Masanao Naya, Satoru Chiba, Satoshi Yamada, Osamu Manabe, Yasuka Kikuchi, Noriko Oyama-Manabe, Koji Oba, Hiroyuki Tsutsui
    Circulation journal : official journal of the Japanese Circulation Society 78 (10) 2468 - 76 1346-9843 2014 [Refereed][Not invited]
     
    BACKGROUND: Fractional flow reserve (FFR) measured on catheterization is now widely used for the diagnosis of functional myocardial ischemia in patients with coronary artery disease (CAD). FFR, however, is invasive and carries potential procedural complications. Therefore, the aim of this study was to compare the diagnostic capability in functionally significant stenosis identified on FFR, between cardiac magnetic resonance myocardial perfusion imaging (CMR-MPI), single-photon emission computed tomography MPI (SPECT-MPI), and dobutamine stress echocardiography (DSE) in patients with CAD. METHODS AND RESULTS: A total of 25 patients who had at least 1 angiographic stenosis ≥50% on coronary angiography was studied. CMR-MPI, SPECT-MPI and DSE were done before FFR measurement. FFR was measured in all 3 major epicardial coronary arteries. Out of 71 vascular territories excluding 4 territories due to inadequate imaging, 29 (41%) had FFR <0.80. The sensitivity of CMR-MPI was significantly higher than that of SPECT-MPI and DSE (P=0.02 and P=0.001, respectively). The area under the receiver operating characteristic curve (AUC) for CMR-MPI (AUC, 0.92) was significantly greater than for SPECT-MPI (AUC, 0.73; P=0.006) and DSE (AUC, 0.69; P<0.001). CONCLUSIONS: CMR-MPI performed well in the detection of functionally significant stenosis defined according to FFR, and had the highest diagnostic sensitivity among the 3 modalities tested in patients with CAD.
  • Yasuka Kikuchi, Noriko Oyama-Manabe, Osamu Manabe, Masanao Naya, Yoichi M Ito, Kanako C Hatanaka, Hiroyuki Tsutsui, Satoshi Terae, Nagara Tamaki, Hiroki Shirato
    European journal of nuclear medicine and molecular imaging 40 (9) 1337 - 44 1619-7070 2013/09 [Refereed][Not invited]
     
    PURPOSE: To investigate the specific imaging findings of multidetector row CT (MDCT) and PET/CT with(18)F-FDG in cardiac dominant diffuse large B-cell lymphoma (DLBCL) in comparison with other cardiac tumours. METHODS: Five patients with DLBCL and 12 patients with other cardiac tumours including pericardial tumours were retrospectively reviewed. Among the patients with other cardiac tumours, seven had metastatic tumours, three had benign tumours, and two had other malignant cardiac tumours. The location of the cardiac mass, the encasement of the coronary artery surrounded by the mass, and pericardial effusion were evaluated using MDCT. The disease activity of the cardiac tumour was also evaluated by PET/CT. RESULTS: Four of the five DLBCL patients had primarily right-sided cardiac lesions, which was seen significantly more frequently in DLBCL than in other cardiac tumours (p = 0.028). All cardiac DLBCL lesions were located around the atrioventricular groove and encased the coronary arteries. ECG-gated cardiac MDCT showed that there was no apparent stenosis of the coronary arteries. Large amounts of pericardial effusion were seen in all DLBCL patients. PET/CT revealed significantly higher FDG uptake in DLBCL than in other cardiac malignant tumours, with no overlap (p = 0.0007). CONCLUSION: The combination of a right-sided cardiac mass with a large pericardial effusion and no apparent stenosis of the encased coronary artery revealed by MDCT and a high maximum standard uptake value were the specific findings in cardiac dominant DLBCL.
  • Masanao Naya, Venkatesh L. Murthy, Marcelo F. Di Carli
    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 62 (12) 1129 - 1129 0735-1097 2013/09 [Refereed][Not invited]
  • Atsuro Masuda, Osamu Manabe, Masanao Naya, Noriko Oyama-Manabe, Shiro Yamada, Shouji Matsushima, Florian C Gaertner, Satoshi Yamada, Hiroyuki Tsutsui, Nagara Tamaki
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 20 (4) 641 - 3 1071-3581 2013/08 [Refereed][Not invited]
  • Masanao Naya, Venkatesh L. Murthy, Courtney R. Foster, Mariya Gaber, Josh Klein, Jon Hainer, Sharmila Dorbala, Ron Blankstein, Marcelo F. Di Carli
    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 61 (20) 2098 - 2106 0735-1097 2013/05 [Refereed][Not invited]
     
    Objectives This study sought to evaluate the interrelation of atherosclerotic burden, as assessed by coronary artery calcium (CAC) score and coronary vascular function, as assessed by quantitative estimates of coronary flow reserve (CFR), with respect to prediction of clinical outcomes. Background The contribution of coronary vascular dysfunction, atherosclerotic burden, and the 2 combined to cardiac events is unknown. Method A total of 901 consecutive patients underwent (82)Rubidium myocardial perfusion imaging (MPI) positron emission tomography (PET) and CAC scan. All patients had normal MPI. The primary endpoint was a composite of major adverse cardiac events (MACE) including cardiac death, nonfatal myocardial infarction, late revascularization, and admission for heart failure. Results At baseline, CFR decreased (2.15 +/- 0.72, 2.02 +/- 0.65, and 1.88 +/- 0.64, p < 0.0001) with increasing levels of CAC (0, 1 to 399, and >= 400). Over a median of 1.53 years (interquartile range: 0.77 to 2.44), there were 57 MACE. Annual risk-adjusted MACE rates were higher for patients with CFR <2.0 compared with >= 2.0 (1.9 vs. 5.5%/ year, p = 0.0007) but were only borderline associated with CAC (3.1%, 3.4%, and 6.2%/year for CAC of 0, 1 to 399, and >= 400, respectively; p = 0.09). Annualized adjusted MACE was increased in the presence of impaired CFR even among patients with CAC = 0 (1.4% vs. 5.2%, p = 0.03). Cox proportional hazards analysis revealed that CFR improved model fit, risk discrimination, and risk reclassification over clinical risk, whereas CAC only modestly improved model fit without improving risk discrimination or reclassification. Conclusions In symptomatic patients with normal MPI, global CFR but not CAC provides significant incremental risk stratification over clinical risk score for prediction of major adverse cardiac events. (C) 2013 by the American College of Cardiology Foundation
  • Michael Osborne, Swathy Kolli, Robert F. Padera, Masanao Naya, Eldrin Lewis, Sharmila Dorbala, Marcelo F. Di Carli, Ron Blankstein
    JOURNAL OF NUCLEAR CARDIOLOGY 20 (2) 310 - 312 1071-3581 2013/04 [Refereed][Not invited]
  • Satoru Chiba, Masanao Naya, Hiroyuki Iwano, Keiichiro Yoshinaga, Chietsugu Katoh, Osamu Manabe, Satoshi Yamada, Satoru Wakasa, Suguru Kubota, Yoshiro Matsui, Nagara Tamaki, Hiroyuki Tsutsui
    European journal of nuclear medicine and molecular imaging 40 (3) 349 - 55 1619-7070 2013/02 [Refereed][Not invited]
     
    PURPOSE: Diastolic function is impaired in patients with end-stage heart failure. Favorable structural changes by surgical ventricular reconstruction (SVR) are thought to improve diastolic function, however, previous studies reported the contradictory results. We hypothesized that cardiac oxidative metabolism and diastolic dysfunction might improve in parallel to the reduction of left ventricular chamber size after SVR. METHODS: We studied 11 patients underwent SVR associated with mitral valve repair for end-stage heart failure due to dilated cardiomyopathy. Diastolic function was assessed by echocardiography and myocardial oxidative metabolism was measured by the monoexponential clearance (k-mono) of (11)C-acetate positron emission tomography at baseline and 1 month after SVR. RESULTS: All patients had preoperative severe diastolic dysfunction [E/A 4.11 ± 1.18, deceleration time (DT) 134 ± 26 ms]. The study patients were divided into 2 groups according to the changes in diastolic function after SVR; unchanged or worsened diastolic function in 6 patients (55 %, Non-responder) and improved diastolic function in 5 (45 %, Responder). K-mono and wall stress decreased only in responder. The changes in k-mono before and after SVR correlated with those in deceleration time (r =  -0.63; p < 0.05) and wall stress (r = 0.75; p < 0.01). CONCLUSIONS: Improvement of diastolic dysfunction in patients with end-stage heart failure by SVR was in parallel to that in oxidative metabolism. It suggests that SVR reduced excessive metabolism during the diastolic phase, in part, via the improvement in diastolic function and the reduction in LV wall stress.
  • Alisa Klaipetch, Osamu Manabe, Noriko Oyama-Manabe, Satoru Chiba, Masanao Naya, Shiro Yamada, Kenji Hirata, Hiroyuki Tsutsui, Nagara Tamaki
    Clinical nuclear medicine 37 (12) 1184 - 5 0363-9762 2012/12 [Refereed][Not invited]
     
    We report the usefulness of F-FDG PET/CT for the detection and therapy evaluation of the infective vegetation. A 64-year-old man with history of aortic valve replacement presented with 2 months of fever without identifiable cause. Echocardiogram showed no inflammation vegetation or abnormality of mechanical valve function. FDG PET/CT with 50 IU/kg IV heparin revealed focal uptakes near the mechanical aortic valve. After antibiotics therapy, fever was ameliorated, and FDG PET/CT findings showed markedly decreased uptake of the lesions. FDG PET/CT is a powerful tool to detect endocarditis even in patients with no anatomical abnormalities.
  • Venkatesh L. Murthy, Masanao Naya, Courtney R. Foster, Mariya Gaber, Jon Hainer, Josh Klein, Sharmila Dorbala, Ron Blankstein, Marcelo F. Di Carli
    CIRCULATION 126 (15) 1858 - U178 0009-7322 2012/10 [Refereed][Not invited]
     
    Background-Diabetes mellitus increases the risk of adverse cardiac outcomes and is considered a coronary artery disease (CAD) equivalent. We examined whether coronary vascular dysfunction, an early manifestation of CAD, accounts for increased risk among diabetics compared with nondiabetics. Methods and Results-A total of 2783 consecutive patients (1172 diabetics and 1611 nondiabetics) underwent quantification of coronary flow reserve (CFR; CFR=stress divided by rest myocardial blood flow) by positron emission tomography and were followed up for a median of 1.4 years (quartile 1-3, 0.7-3.2 years). The primary end point was cardiac death. Impaired CFR (below the median) was associated with an adjusted 3.2- and 4.9-fold increase in the rate of cardiac death for diabetics and nondiabetics, respectively (P=0.0004). Addition of CFR to clinical and imaging risk models improved risk discrimination for both diabetics and nondiabetics (c index, 0.77-0.79, P=0.04; 0.82-0.85, P=0.03, respectively). Diabetic patients without known CAD with impaired CFR experienced a rate of cardiac death comparable to that for nondiabetic patients with known CAD (2.8%/y versus 2.0%/y; P=0.33). Conversely, diabetics without known CAD and preserved CFR had very low annualized cardiac mortality, which was similar to patients without known CAD or diabetes mellitus and normal stress perfusion and systolic function (0.3%/y versus 0.5%/y; P=0.65). Conclusions-Coronary vasodilator dysfunction is a powerful, independent correlate of cardiac mortality among both diabetics and nondiabetics and provides meaningful incremental risk stratification. Among diabetic patients without CAD, those with impaired CFR have event rates comparable to those of patients with prior CAD, whereas those with preserved CFR have event rates comparable to those of nondiabetics. (Circulation. 2012;126:1858-1868.)
  • Venkatesh L. Murthy, Masanao Naya, Courtney R. Foster, Jon Hainer, Mariya Gaber, Sharmila Dorbala, David M. Charytan, Ron Blankstein, Marcelo F. Di Carli
    JACC-CARDIOVASCULAR IMAGING 5 (10) 1025 - 1034 1936-878X 2012/10 [Refereed][Not invited]
     
    OBJECTIVES This study sought to evaluate whether impaired vasodilator function, an early manifestation of coronary artery disease, which precedes angiographic stenosis, accounts for increased risk among patients with moderate to severe renal dysfunction. BACKGROUND Patients with renal dysfunction are at increased risk of adverse cardiac outcomes, even in the absence of overt myocardial ischemia or infarction. METHODS We included 866 consecutive patients with moderate to severe renal dysfunction referred for rest and stress myocardial perfusion positron emission tomography and followed them for a median of 1.28 years (interquartile range: 0.64 to 2.34). Regional myocardial perfusion abnormalities were assessed by semiquantitative visual analysis of positron emission tomography images. Rest and stress myocardial blood flow were calculated using factor analysis and a 2-compartment kinetic model; they were also used to compute coronary flow reserve (stress/rest myocardial blood flow). The primary endpoint was cardiac death. RESULTS Overall, 3-year cardiac mortality was 16.2%. After adjusting for clinical risk, left ventricular ejection fraction, as well as the magnitude of scar and/or ischemia, coronary flow reserve below the median (<1.5) was associated with a 2.1-fold increase in the risk of cardiac death (95% confidence interval [CI]: 1.3 to 3.5, p = 0.004). Incorporation of coronary flow reserve into cardiac death risk assessment models resulted in an increase in the C-index from 0.75 to 0.77 (p = 0.05) and in a net reclassification improvement of 0.142 (95% CI: 0.076 to 0.219). Among patients at intermediate risk based on all data other than coronary flow reserve, the net reclassification improvement was 0.489 (95% CI: 0.192 to 0.836). Corresponding improvements in risk assessment for mortality from any cause were also demonstrated. CONCLUSIONS The presence of coronary vascular dysfunction in patients with moderate to severe renal dysfunction, as assessed by positron emission tomography, is a powerful, independent predictor of cardiac mortality and provides meaningful incremental risk stratification over conventional markers of clinical risk. (J Am Coll Cardiol Img 2012;5:1025-34) (C) 2012 by the American College of Cardiology Foundation
  • Chietsugu Katoh, Keiichiro Yoshinaga, Ran Klein, Katsuhiko Kasai, Yuuki Tomiyama, Osamu Manabe, Masanao Naya, Mamoru Sakakibara, Hiroyuki Tsutsui, Robert A deKemp, Nagara Tamaki
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 19 (4) 763 - 74 1071-3581 2012/08 [Refereed][Not invited]
     
    PURPOSE: Myocardial blood flow (MBF) estimation with (82)Rubidium ((82)Rb) positron emission tomography (PET) is technically difficult because of the high spillover between regions of interest, especially due to the long positron range. We sought to develop a new algorithm to reduce the spillover in image-derived blood activity curves, using non-uniform weighted least-squares fitting. METHODS: Fourteen volunteers underwent imaging with both 3-dimensional (3D) (82)Rb and (15)O-water PET at rest and during pharmacological stress. Whole left ventricular (LV) (82)Rb MBF was estimated using a one-compartment model, including a myocardium-to-blood spillover correction to estimate the corresponding blood input function Ca(t)(whole). Regional K1 values were calculated using this uniform global input function, which simplifies equations and enables robust estimation of MBF. To assess the robustness of the modified algorithm, inter-operator repeatability of 3D (82)Rb MBF was compared with a previously established method. RESULTS: Whole LV correlation of (82)Rb MBF with (15)O-water MBF was better (P < .01) with the modified spillover correction method (r = 0.92 vs r = 0.60). The modified method also yielded significantly improved inter-operator repeatability of regional MBF quantification (r = 0.89) versus the established method (r = 0.82) (P < .01). CONCLUSION: A uniform global input function can suppress LV spillover into the image-derived blood input function, resulting in improved precision for MBF quantification with 3D (82)Rb PET.
  • Integrating semiquantitative measures of myocardial ischemia and quantitative coronary flow reserve assessed by 82Rubidium PET for the detection of multivessel coronary artery disease
    Naya Masanao, Murthy Venkatesh, Klein Josh, Foster Courtney, Gaber Mariya, Oba Koji, Dorbala Sharmila, Hainer Jon, Resnic Frederic, Di Carli Marcelo
    JOURNAL OF NUCLEAR MEDICINE 53 0161-5505 2012/05/01 [Refereed][Not invited]
  • Venkatesh L. Murthy, Masanao Naya, Courtney R. Foster, Jon Hainer, Mariya Gaber, Gilda Di Carli, Ron Blankstein, Sharmila Dorbala, Arkadiusz Sitek, Michael J. Pencina, Marcelo F. Di Carli
    CIRCULATION 124 (20) 2215 - 2224 0009-7322 2011/11 [Refereed][Not invited]
     
    Background-Impaired vasodilator function is an early manifestation of coronary artery disease and may precede angiographic stenosis. It is unknown whether noninvasive assessment of coronary vasodilator function in patients with suspected or known coronary artery disease carries incremental prognostic significance. Methods and Results-A total of 2783 consecutive patients referred for rest/stress positron emission tomography were followed up for a median of 1.4 years (interquartile range, 0.7-3.2 years). The extent and severity of perfusion abnormalities were quantified by visual evaluation of myocardial perfusion images. Rest and stress myocardial blood flows were calculated with factor analysis and a 2-compartment kinetic model and were used to compute coronary flow reserve (coronary flow reserve equals stress divided by rest myocardial blood flow). The primary end point was cardiac death. Overall 3-year cardiac mortality was 8.0%. The lowest tertile of coronary flow reserve (<1.5) was associated with a 5.6-fold increase in the risk of cardiac death (95% confidence interval, 2.5-12.4; P<0.0001) compared with the highest tertile. Incorporation of coronary flow reserve into cardiac death risk assessment models resulted in an increase in the c index from 0.82 (95% confidence interval, 0.78-0.86) to 0.84 (95% confidence interval, 0.80-0.87; P=0.02) and in a net reclassification improvement of 0.098 (95% confidence interval, 0.025-0.180). Addition of coronary flow reserve resulted in correct reclassification of 34.8% of intermediate-risk patients (net reclassification improvement=0.487; 95% confidence interval, 0.262-0.731). Corresponding improvements in risk assessment for mortality from any cause were also demonstrated. Conclusion-Noninvasive quantitative assessment of coronary vasodilator function with positron emission tomography is a powerful, independent predictor of cardiac mortality in patients with known or suspected coronary artery disease and provides meaningful incremental risk stratification over clinical and gated myocardial perfusion imaging variables. (Circulation. 2011;124:2215-2224.)
  • Masanao Naya, Venkatesh L. Murthy, Ron Blankstein, Arkadiusz Sitek, Jon Hainer, Courtney Foster, Mariya Gaber, Jolene M. Fantony, Sharmila Dorbala, Marcelo F. Di Carli
    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 58 (17) 1807 - 1816 0735-1097 2011/10 [Refereed][Not invited]
     
    Objectives The purpose of this study was to quantify the effects of coronary atherosclerosis morphology and extent on myocardial flow reserve (MFR). Background Although the relationship between coronary stenosis and myocardial perfusion is well established, little is known about the contribution of other anatomic descriptors of atherosclerosis burden to this relationship. Methods We evaluated the relationship between atherosclerosis plaque burden, morphology, and composition and regional MFR (MFR(regional)) in 73 consecutive patients undergoing Rubidium-82 positron emission tomography and coronary computed tomography angiography for the evaluation of known or suspected coronary artery disease. Results Atherosclerosis was seen in 51 of 73 patients and in 107 of 209 assessable coronary arteries. On a per-vessel basis, the percentage diameter stenosis (p = 0.02) or summed stenosis score (p = 0.002), integrating stenoses in series, was the best predictor of MFR(regional). Importantly, MFR(regional) varied widely within each coronary stenosis category, even in vessels with nonobstructive plaques (n = 169), 38% of which had abnormal MFR(regional) (<2.0). Total plaque length, composition, and remodeling index were not associated with lower MFR. On a per-patient basis, the modified Duke CAD (coronary artery disease) index (p = 0.04) and the number of segments with mixed plaque (p = 0.01) were the best predictors of low MFR(global). Conclusions Computed tomography angiography descriptors of atherosclerosis had only a modest effect on downstream MFR. On a per-patient basis, the extent and severity of atherosclerosis as assessed by the modified Duke CAD index and the number of coronary segments with mixed plaque were associated with decreased MFR. (J Am Coll Cardiol 2011;58:1807-16) (C) 2011 by the American College of Cardiology Foundation
  • Takashi Sugiki, Masanao Naya, Osamu Manabe, Satoru Wakasa, Suguru Kubota, Satoru Chiba, Hiroyuki Iwano, Satoshi Yamada, Keiichiro Yoshinaga, Nagara Tamaki, Hiroyuki Tsutsui, Yoshiro Matsui
    JACC. Cardiovascular imaging 4 (7) 762 - 70 1936-878X 2011/07 [Refereed][Not invited]
     
    OBJECTIVES: The aim of this study was to investigate the effects of surgical ventricular reconstruction (SVR) on cardiac efficiency as a surrogate marker for cardiac function and oxidative metabolism in patients with severe heart failure. BACKGROUND: Our new integrated overlapping left ventriculoplasty, modified SVR, combined with mitral complex reconstruction, reduce left ventricular (LV) volume associated with improvement of symptoms of heart failure. METHODS: Twelve consecutive patients with end-stage heart failure due to nonischemic dilated cardiomyopathy (DCM) (n = 6) and ischemic dilated cardiomyopathy (ICM) (n = 6) who underwent SVR were studied. Myocardial oxidative metabolism per gram of tissue was estimated by monoexponential clearance of (11)C-acetate positron emission tomography (K(mono)). Forward stroke volume at the LV outflow tract was measured by echocardiography. Cardiac efficiency was estimated by the ratio of external work (stroke volume at the LV outflow tract index × systolic blood pressure × heart rate) to K(mono) before and 1 month after SVR. RESULTS: After SVR, medians of New York Heart Association functional class significantly improved from 3 to 1.5 (p < 0.01) in both DCM and ICM patients. End-systolic and end-diastolic volume and LV mass significantly decreased in both groups. Stroke volume at the LV outflow tract increased from 43 ± 8 ml to 52 ± 11 ml (p = 0.028) in DCM patients, but not in ICM patients (49 ± 21 ml to 59 ± 26 ml, p = 0.12). K(mono) × LV mass, as an index of global LV oxidative metabolism, decreased in DCM patients (13.6 ± 1.9 g/min vs. 8.6 ± 1.5 g/min, p = 0.03) and ICM patients (12.0 ± 3.4 g/min vs. 9.2 ± 1.0 g/min, p = 0.06). As a result, cardiac efficiency increased in all patients with DCM (3.34 ± 0.46 × 10E6 vs. 4.74 ± 0.88 × 10E6 mm Hg·ml·min/m(2), p = 0.03) and in 5 of 6 patients with ICM (4.54 ± 1.66 × 10E6 vs. 5.99 ± 2.11 × 10E6 mm Hg·ml·min/m(2), p = 0.12). CONCLUSIONS: Combined surgery with SVR and mitral complex reconstruction reduced LV volume in association with improvement of cardiac efficiency in patients with severe heart failure.
  • Masanao Naya, Koichi Morita, Keiichiro Yoshinaga, Osamu Manabe, Daisuke Goto, Kenji Hirata, Chietsugu Katoh, Nagara Tamaki, Hiroyuki Tsutsui
    European journal of nuclear medicine and molecular imaging 38 (3) 491 - 8 1619-7070 2011/03 [Refereed][Not invited]
     
    PURPOSE: Smoking cessation has been shown to normalize the coronary endothelial dysfunction in healthy young smokers. However, its effect has not been explored in middle-aged smokers with a longer history of smoking. Therefore, we compared the effects of smoking cessation on coronary vasomotor response between both young and middle-aged smokers and identified the predictor for its improvement. METHODS: This study investigated 14 young healthy smokers (age 25.2 ± 2.3 years), 13 middle-aged smokers (age 42.0 ± 6.5 years) and 10 non-smokers. Myocardial blood flow (MBF) was measured by using (15)O-water positron emission tomography (PET). RESULTS: At baseline, the ratio of MBF during the cold pressor test (CPT) to that at rest (MBF(CPT/rest)), the index of coronary endothelial function, was significantly decreased in both young and middle-aged smokers compared to non-smokers (1.24 ± 0.20 and 1.10 ± 0.39 vs 1.53 ± 0.18, p < 0.05 and p < 0.001, respectively). The ratio of MBF during adenosine triphosphate infusion to that at rest was significantly decreased in middle-aged smokers compared to young smokers and non-smokers (3.34 ± 1.52 vs 4.43 ± 0.92 and 4.69 ± 1.25, p < 0.05, respectively). MBF(CPT/rest) at 1 month after smoking cessation significantly increased in young smokers, but not in middle-aged smokers. By multivariate analysis, baseline serum malondialdehyde-modified low-density lipoprotein (MDA-LDL) was an independent predictor for the changes in MBF(CPT/rest) after smoking cessation (β = -0.45, p < 0.05). CONCLUSION: Coronary endothelial dysfunction was reversible by short-term smoking cessation in young smokers, but not in middle-aged smokers, which was associated with serum MDA-LDL levels. Long-term smoking exposure could lead to more advanced coronary endothelial dysfunction and atherosclerosis possibly via oxidative stress.
  • Incremental diagnostic value of regional myocardial blood flow quantification over relative perfusion imaging with generator-produced rubidium-82 PET.
    Keiichiro Yoshinaga, Chietsugu Katoh, Osamu Manabe, Ran Klein, Masanao Naya, Mamoru Sakakibara, Shiro Yamada, Robert A Dekemp, Hiroyuki Tsutsui, Nagara Tamaki
    Circulation journal : official journal of the Japanese Circulation Society 75 (11) 2628 - 34 1346-9843 2011 [Refereed][Not invited]
     
    BACKGROUND: Myocardial blood flow (MBF) can be measured with positron emission tomography (PET) and its quantification should provide diagnostic information beyond that obtained through standard visual analysis. However, this possibility has not been fully studied with PET and generator-produced rubidium-82 (⁸²Rb). We evaluated regional MBF in segments with and without ischemia using ⁸²Rb PET in patients with coronary artery disease (CAD). METHODS AND RESULTS: Rest and stress ⁸²Rb PET and coronary angiography were performed for 12 patients with CAD. Based on angiography and relative ⁸²Rb perfusion images, segments were classified into 4 groups (Group A: myocardial ischemia with >70% diameter stenosis; Group B: no ischemia with stenosis; Group C: no ischemia without stenosis; Group D: ischemia without stenosis). Rest MBF was similar among the 4 groups. Groups A and B showed reduced hyperemic MBF compared with Group C (P < 0.05 vs. Group C) [Group A (n=16) 1.28 ± 0.58 ml·min⁻¹·g⁻¹; Group B (n=11) 1.72 ± 0.64 ml·min⁻¹·g⁻¹; Group C (n=9) 2.60 ± 1.09 ml·min⁻¹·g⁻¹; Group D (n=2) 2.33 ml·min⁻¹·g⁻¹]. Coronary flow reserves were inversely correlated with percent diameter stenosis (r=0.76, P < 0.0001). CONCLUSIONS: Segments with ischemia and coronary stenosis had reduced hyperemic MBF. Segments with coronary stenosis without ischemia also had reduced hyperemic MBF compared with non-stenotic segments. MBF quantification using ⁸²Rb PET may provide additional diagnostic information.
  • Keiichiro Yoshinaga, Osamu Manabe, Chietsugu Katoh, Li Chen, Ran Klein, Masanao Naya, Robert A deKemp, Kathryn Williams, Rob S B Beanlands, Nagara Tamaki
    European journal of nuclear medicine and molecular imaging 37 (12) 2233 - 41 1619-7070 2010/12 [Refereed][Not invited]
     
    PURPOSE: Endothelial dysfunction is the earliest abnormality in the development of coronary atherosclerosis. 82Rb is a generator-produced positron emission tomography (PET) myocardial perfusion tracer that is becoming more widely used. We aimed to (1) develop a method for quantitative assessment of coronary endothelial function using the myocardial blood flow (MBF) response during a cold pressor test (CPT) in smokers, measured using 82Rb PET, and (2) compare the results with those measured using 15O-water PET. METHODS: MBF was assessed at rest and during the CPT with 82Rb and 15O-water in nine controls and ten smokers. A one-compartment model with tracer extraction correction was used to estimate MBF with both tracers. CPT response was calculated as the ratio of MBF during the CPT to MBF at rest. RESULTS: At rest, measurements of MBF for smokers vs controls were not different using 15O-water (0.86±0.18 vs 0.70±0.13, p=0.426) than they were using 82Rb (0.83±0.23 vs 0.62±0.20, p=0.051). Both methods showed a reduced CPT response in smokers vs controls (15O-water, 1.03±0.21 vs 1.42±0.29, p=0.006; 82Rb, 1.02±0.28 vs 1.70±0.52, p<0.001). There was high reliability [intraclass correlation coefficients: 0.48 (0.07, 0.75)] of MBF measurement between 82Rb and 15O-water during the CPT. CONCLUSION: Using a CPT, 82Rb MBF measurements detected coronary endothelial dysfunctions in smokers. 82Rb MBF measurements were comparable to those made using the 15O-water approach. Thus, 82Rb PET may be applicable for risk assessments or evaluation of risk factor modification in subjects with coronary risk factors.
  • Masanao Naya, Satoru Chiba, Hiroyuki Iwano, Satoshi Yamada, Chietsugu Katoh, Osamu Manabe, Keiichiro Yoshinaga, Yoshiro Matsui, Nagara Tamaki, Hiroyuki Tsutsui
    European journal of nuclear medicine and molecular imaging 37 (12) 2242 - 8 1619-7070 2010/12 [Refereed][Not invited]
     
    PURPOSE: The relationship between myocardial oxidative metabolism and pressure overload in aortic valve stenosis (AS) is not fully elucidated. We identified the determinants of myocardial oxidative metabolism by measuring its changes after aortic valve replacement (AVR) in patients with AS. METHODS: Myocardial 11C-acetate clearance rate constant (Kmono), an index of oxidative metabolism, was measured non-invasively by using positron emission tomography in 16 patients with moderate to severe AS and 7 healthy controls. The severity of AS was assessed by echocardiography. Of 16 patients, 5 were reexamined at 1 month after AVR. RESULTS: Kmono was significantly higher in patients with AS than healthy controls by 42% (0.068±0.014 vs 0.048±0.007/min, p<0.01). Kmono was significantly correlated with age (r=0.58, p<0.01), left ventricular (LV) mass index (r=0.61, p<0.01) and estimated systolic LV pressure (r=0.81, p<0.001) measured by echocardiography. By multivariate analysis, estimated LV systolic pressure was an independent predictor of Kmono (β=0.93, p<0.01). After AVR, Kmono (from 0.075±0.012 to 0.061±0.014/min, p=0.043) and LV mass index (from 183±49 to 124±41 g/ml2, p=0.043) were significantly decreased despite no significant changes in rate-pressure product. CONCLUSION: Myocardial oxygen metabolism was increased in patients with AS, which was decreased after AVR. The increased myocardial oxidative metabolism in AS was largely attributable to the pressure overload of the LV.
  • Nagara Tamaki, Keiichiro Yoshinaga, Masanao Naya
    EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 37 (6) 1213 - 1224 1619-7070 2010/06 [Refereed][Not invited]
     
    Cardiac PET has the unique ability to assess coronary flow reserve and coronary endothelial function on the basis of response of blood flow to pharmacological stress and the cold pressor test. Quantitative analysis of coronary vasomotor function is valuable for precise assessment of function and treatment monitoring in the presence of various coronary risk factors. In addition, recent data have shown prognostic value of PET assessment of coronary vasomotor imaging in patients with suspected coronary artery disease. Thus, quantitative analysis of PET has a great potential for wide application in identifying microcirculatory dysfunction and "individualized" monitoring of the effects of primary or preventive medical intervention to optimize cardiovascular outcome.
  • Masanao Naya, Takahiro Tsukamoto, Koichi Morita, Chietsugu Katoh, Kenichi Nishijima, Hiroshi Komatsu, Satoshi Yamada, Yuji Kuge, Nagara Tamaki, Hiroyuki Tsutsui
    JOURNAL OF NUCLEAR MEDICINE 50 (2) 220 - 225 0161-5505 2009/02 [Refereed][Not invited]
     
    We evaluated whether myocardial P-adrenergic receptor (beta-AR) density, as determined by (11)C-CGP12177 PET, could predict improvement of cardiac function by P-blocker carvedilol treatment in patients with idiopathic dilated cardiomyopathy (IDC). Methods: Ten patients with IDC (left ventricular ejection fraction [LVEF] < 45%) were studied. Myocardial PAR density was estimated using (11)C-CGP12177 PET before treatment with carvedilol. Changes of LVEF in response to dobutamine infusion (ALVEF-dobutamine) were also measured by echocardiography. Changes of LVEF (Delta LVEF-carvedilol) were evaluated after 20 mo of carvedilol treatment. Results: Baseline myocardial PAR density significantly correlated with Delta LVEF-carvedilol (r = -0.88, P < 0.001). In contrast, Delta LVEF-clobutamine did not correlate with Delta LVEF-carvedilol (P = 0.65). Myocardial PAR density was the significant multivariate independent predictor of Delta LVEF-carvedilol (p = -0.88, P < 0.001) among univariate predictors, including functional class (r = 0.76, P < 0.05), plasma norepinephrine (r = 0.85, P < 0.01), LVEF (r = -0.64, P < 0.05), and age as confounding factors. Furthermore, myocardial PAR density was significantly correlated with plasma norepinephrine (r = -0.79, P < 0.01) and LVEF (r = 0.70, P < 0.05). Conclusion: Myocardial PAR density is more tightly related to improvement of LVEF-carvedilol than is cardiac contractile reserve in patients with IDC. Patients with decreased myocardial PAR have higher resting adrenergic drive, as reflected by plasma norepinephrine, and may receive greater benefit from being treated by antiadrenergic drugs.
  • Osamu Manabe, Keiichiro Yoshinaga, Chietsugu Katoh, Masanao Naya, Robert A deKemp, Nagara Tamaki
    Journal of nuclear medicine : official publication, Society of Nuclear Medicine 50 (1) 68 - 71 0161-5505 2009/01 [Refereed][Not invited]
     
    UNLABELLED: The repeatability of rest and hyperemic myocardial blood flow (MBF) measurements using 82Rb PET has not been evaluated. The aim of this study was to investigate the short-term repeatability of such measurements. METHODS: Fifteen healthy volunteers underwent rest and pharmacologic stress 82Rb PET, repeated 60 min apart. RESULTS: There was no significant difference in repeated rest MBF (0.77+/-0.25 vs. 0.82+/-0.25 mL/min/g, P=0.31; mean difference, 6.18%+/-12.22%) or repeated hyperemic MBF (3.35+/-1.37 vs. 3.39+/-1.37 mL/min/g, P=0.81; mean difference, 1.17%+/-13.64%). The repeatability coefficients were 0.19 mL/min/g for rest MBF and 0.92 mL/min/g for hyperemia. CONCLUSION: MBF using 82Rb is highly reproducible using a same-day short-term repeatability protocol. Serial MBF measurements with 82Rb PET should have the ability to quantify the acute effects of therapeutic interventions on MBF.
  • Heterogeneous reduction of myocardial oxidative metabolism in patients with ischemic and dilated cardiomyopathy using C-11 acetate PET.
    Wu YW, Naya M, Tsukamoto T, Komatsu H, Morita K, Yoshinaga K, Kuge Y, Tsutsui H, Tamaki N
    Circulation journal : official journal of the Japanese Circulation Society 72 (5) 786 - 792 1346-9843 2008/05 [Refereed][Not invited]
  • Takahiro Tsukamoto, Koichi Morita, Masanao Naya, Masayuki Inubushi, Chietsugu Katoh, Kenichi Nishijima, Yuji Kuge, Hiroshi Okamoto, Hiroyuki Tsutsui, Nagara Tamaki
    JOURNAL OF NUCLEAR MEDICINE 48 (11) 1777 - 1782 0161-5505 2007/11 [Refereed][Not invited]
     
    Cardiac sympathetic function plays an important role in the regulation of left ventricular (LV) function and the pathophysiology of LV dysfunction. C-11-CGP-12177 (C-11-CGP) has been used to assess myocardial beta-adrenergic receptor (P-AR) density in vivo using PET. The aim of this study is to measure myocardial P-AR density in patients with nonischemic cardiomyopathy and to compare the measurements with various standard parameters of heart failure (HF), particularly with presynaptic function assessed by I-123-metaiodobenzy(guanidine (I-123-MIBG) imaging. Methods: C-11-CGP PET was performed on 16 patients with nonischemic cardiomyopathy and 8 age-matched healthy volunteers using a double injection method. A C-11-CGP dynamic scan for 75 min was performed after the injection of C-11-CGP with a high specific activity. After 30 min, C-11-CGP with a low specific activity was injected. The P-AR density of the whole LV was calculated on the basis of the graphical analysis method. Additionally, beta-AR density was compared with LV ejection fraction (LVEF), sympathetic presynaptic function assessed using I-123-MIBG kinetics, and neurohormonal parameters. Results: The P-AR density of patients was significantly lower than that of healthy volunteers (3.80 +/- 0.96 vs. 7.70 +/- 1.92 pmol/mL; P < 0.0001). In the patients, P-AR density correlated significantly with LVEF (r = 0.62, P < 0.05). Furthermore, P-AR density correlated significantly with the I-123-MIBG washout rate (r = -0.68, P < 0.01) and delayed heart-to-mediastinum ratio (H/M ratio) (r = 0.61, P < 0.05). On the other hand, the correlation between P-AR density and early H/M ratio was not significant (r = 0.40, P = 0.13). The beta-AR density of patients with severe HF (New York Heart Association functional [NYHA] class III) was significantly lower than that of those with NYHA functional class I or class II HIF (3.24 +/- 0.96 vs. 4.24 +/- 0.73 pmol/mL; P < 0.05). Conclusion: A reduction in P-AR density measured by C-11-CGP PET was observed in patientswith nonischemic cardiomyopathy. This downregulation may be due to the increased presynaptic sympathetic tone as assessed by I-123-MIBG imaging.
  • Masanao Naya, Takahiro Tsukamoto, Koichi Morita, Chietsugu Katoh, Tornoo Furumoto, Satoshi Fujii, Nagara Tamaki, Hiroyuki Tsutsui
    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 50 (12) 1144 - 1149 0735-1097 2007/09 [Refereed][Not invited]
     
    Objectives We aimed to compare the effects of the angiotensin II receptor blocker (ARB) olmesartan versus the calcium channel blocker (CCB) amlodipine on coronary endothelial dysfunction in patients with hypertension. Background Angiotensin II receptor blockers are thought to have greater beneficial effects than CCBs on coronary vasomotion by directly blocking action of angiotensin II. Methods Twenty-six patients with untreated essential hypertension were prospectively assigned to treatment with either olmesartan (27.7 +/- 12.4 mg/day, n = 13) or amlodipine (5.6 +/- 1.5 mg/day, n = 13) for 12 weeks. Changes of corrected myocardial blood flow (Delta MBF) and coronary vascular resistance (Delta CVR) from rest to cold pressor were measured by using O-15-water and positron emission tomography before and after treatment. Blood biomarkers including lipids, glucose, insulin, high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and superoxide dismutase (SOD) were also measured. Results Olmesartan and amlodipine reduced blood pressure (BP) to the same extent (-28.7 +/- 16.2 mm Hg vs. -26.7 +/- 10.8 mm Hg). In the olmesartan group, Delta MBF tended to be greater (-0.15 +/- 0.19 ml/g/min vs. 0.03 +/- 0.17 ml/g/min, p = 0.09 by 2-way analysis of variance), and Delta CVR was significantly decreased (7.9 +/- 23.5 mm Hg/[ml/g/min] vs. -16.6 +/- 18.0 mm Hg/[ml/g/min], p < 0.05) after treatment, whereas these parameters did not change in the amlodipine group (Delta MBF: -0.15 - 0.12 ml/g/min vs. -0.12 +/- 0.20 ml/g/min; Delta CVR: 6.5 +/- :18.2 mm Hg/[ml/g/min] vs. 4.8 +/- 23.4 mm Hg/[ml/g/min]). Serum SOD activity tended to increase (4.74 +/- 4.77 U/ml vs. 5.57 +/- 4.74 U/ml, p = 0.07 by 2-way analysis of variance) only in the olmesartan group. Conclusions Olmesartan, but not amlodipine, improved endothelium-dependent coronary dilation in hypertensive patients independent of BP reduction. These beneficial effects on coronary vasomotion might be via an antioxidant property of ARBs.
  • Masanao Naya, Takahiro Tsukamoto, Koichi Morita, Chietsugu Katoh, Tomoo Furumoto, Satoshi Fujii, Nagara Tamaki, Hiroyuki Tsutsui
    HYPERTENSION RESEARCH 30 (6) 541 - 548 0916-9636 2007/06 [Refereed][Not invited]
     
    Coronary endothelial function is impaired in hypertension; however, the severity of this impairment varies among patients. We aimed to identify the predictors of coronary endothelial dysfunction among clinical variables related to hypertension and atherosclerosis. Twenty-seven untreated, uncomplicated essential hypertensive patients and 10 age-matched healthy controls were studied prospectively. Myocardial blood flow (MBF) was measured by using O-15-water positron emission tomography (PET) at rest and during a cold pressor test (CPT). Coronary vascular resistance (CVR) during CPT was used as a marker of coronary endothelial function. Serum low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, malondialdehyde-LDL, homeostasis model assessment, high-sensitivity C-reactive protein (hs-CRP), and plasma interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha were also measured. CVR during CPT was significantly higher in hypertensive patients than in healthy controls (114 +/- 26 vs. 94 +/- 12 mmHg/[mL/g/min]; p<0.05). By univariate analysis, CVR during CPT was correlated with LDL cholesterol (r=0.38, p<0.05), IL-6 (r=0.46, p<0.02), and TNF-alpha (r=0.39, p<0.05) in hypertensive patients. By multivariate analysis, IL-6 and TNF-a were significant independent predictors of CVR during CPT. Elevated plasma IL-6 and TNF-alpha levels were independent predictors of coronary endothelial dysfunction in hypertensive patients. These results suggest that plasma IL-6 and TNF-alpha might be useful for identifying the high risk subgroup of hypertensive patients with coronary endothelial dysfunction and provide an important clue to link systemic inflammation to the development of coronary atherosclerosis.
  • Elevated plasma plasminogen activator inhibitor type-1 is an independent predictor of coronary microvascular dysfunction in hypertension
    Masanao Naya, Takahiro Tsukamoto, Masayuki Inubushi, Koichi Morita, Chietsugu Katoh, Tomoo Furumoto, Satoshi Fujii, Hiroyuki Tsutsui, Nagara Tamaki
    CIRCULATION JOURNAL 71 (3) 348 - 353 1346-9843 2007/03 [Refereed][Not invited]
     
    Background Elevated plasma plasminogen activator inhibitor-1 (PAI-1) is related to cardiovascular events, but its role in subclinical coronary microvascular. dysfunction remains unknown. Thus, in the present study it was investigated whether elevated plasma PAI-1 activity is associated with coronary microvascular dysfunction in hypertensive patients. Methods and Results Thirty patients with untreated essential hypertension and 10 age-matched healthy controls were studied prospectively. Myocardial blood flow (MBF) was measured by using O-15-water positron emission tomography. Clinical variables associated with atherosclerosis (low-density lipoprotein-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, homeostasis model assessment (HOMA-IR), and PAI-1 activity) were assessed to determine their involvement in coronary microvascular dysfunction. Adenosine triphosphate (ATP)-induced hyperemic MBF and coronary flow reserve (CFR) were significantly lower in hypertensive patients than in healthy controls (ATP-induced MBF: 2.77 +/- 0.82 vs 3.49 +/- 0.71 ml (.) g(-1) (.) min(-1); p < 0.02 and CFR: 2.95 +/- 1.06 vs 4.25 +/- 0.69; p < 0.001). By univariate analysis, CFR was positively correlated with HDL-cholesterol (r=0.46, p < 0.02), and inversely with HOMA-IR (r=-0.39, p < 0.05) and PAI-1 activity (r=-0.61, p < 0.001). By multivariate analysis, elevated PAI-1 activity remained a significant independent determinant of diminished CFR. Conclusions Elevated plasma PAI-1 activity was independently associated with coronary microvascular dysfunction, which suggests that plasma PAI-1 activity is an important clue linking hypofibrinolysis to the development of atherosclerosis.
  • 新しい心臓核医学イメージング -北海道大学での取り組み-
    犬伏正幸, 久下裕司, 塚本隆裕, 納谷昌直, 森田浩一, 玉木長良
    動態核医学 24 1-6  2007 [Refereed][Not invited]
  • Smoking cessation normalizes coronary endothelial vasomotor response assessed with O-15-water and PET in healthy young smokers
    Koichi Morita, Takahiro Tsukamoto, Masanao Naya, Kazuyuki Noriyasu, Masayuki Inubushi, Tohru Shiga, Chietsugu Katoh, Yuji Kuge, Hiroyuki Tsutsui, Nagara Tamaki
    JOURNAL OF NUCLEAR MEDICINE 47 (12) 1914 - 1920 0161-5505 2006/12 [Refereed][Not invited]
     
    Cigarette smoking is one of the risk factors of cardiovascular diseases and is related to abnormal peripheral and coronary vascular vasomotion. Coronary vascular endothelial dysfunction is caused by chronic smoking in smokers without epicardial coronary artery stenosis. The coronary endothelial vasomotion abnormality is restored by interventions such as L-arginine or vitamin C infusion. However, to our knowledge, the effect of smoking cessation on coronary vasomotor response has not been elucidated. Therefore, the aim of this study was to assess the effect of smoking cessation on coronary vasomotor response by quantitative myocardial blood flow (MBF) measurement using O-15-water and PET. Methods: Fifteen young smokers (Brinkman index > 100; mean age +/- SD, 26 +/- 4 y) with no evidence of heart disease or cardiovascular risk factors, except for smoking, and age-matched nonsmokers (n = 12) were enrolled in this study. MBF was measured at rest, during the cold pressor test (CPT), before and at 1 and 6 mo after smoking cessation. In addition, MBF measurement during adenosine triphosphate (ATP) infusion was performed before and at 6 mo after smoking cessation. In nonsmokers, MBF was measured at rest, during ATP infusion, and during the CPT. Results: MBF at rest and during ATP infusion did not differ between smokers and nonsmokers (0.73 +/- 0.12 vs. 0.80 +/- 0.15 mLg/min and 3.15 +/- 1.43 vs. 3.69 +/- 0.76 mL/g/min, respectively; P = not significant). In contrast, MBF during the CPT in smokers was lower than that in nonsmokers (0.90 +/- 0.19 vs. 1.12 +/- 0.28 mUg/min; P < 0.05). There was no significant difference in MBF either at rest or during ATP infusion between before and after smoking cessation, but MBF during the CPT increased at 1 mo in comparison with before cessation of smoking (0.90 +/- 0.19 vs. 1.02 +/- 0.22 mUg/min; P < 0.01). An improvement of MBF response to the CPT was preserved at 6 mo after smoking cessation. Conclusion: Coronary vasomotor abnormality assessed by MBF response to the CPT was improved at 1 mo after smoking cessation. These findings indicate that coronary endothelial dysfunction may be reversible within 1 mo after smoking cessation in healthy young smokers.
  • Takahiro Tsukamoto, Koichi Morita, Masanao Naya, Chietsugu Katoh, Masayuki Inubushi, Yuji Kuge, Hiroyuki Tsutsui, Nagara Tamaki
    EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 33 (10) 1150 - 1156 1619-7070 2006/10 [Refereed][Not invited]
     
    Purpose: Myocardial flow reserve (MFR) measurement has an important role in assessing the functional severity of coronary artery stenosis. However, a discrepancy between the anatomical severity of coronary artery stenosis and MFR is often observed. Such a discrepancy may be explained by coronary risk factors. In this study, we aimed to investigate the influence of coronary artery stenosis severity and risk factors on MFR. Methods: Seventy-four patients suspected to have coronary artery disease and seven age-matched healthy volunteers were enrolled. Myocardial blood flow (MBF) and MFR were measured using O-15-labelled water PET. Regional MFR was calculated in regions with significant coronary artery stenosis (stenotic regions) and in regions without significant stenosis (remote regions). The contributions of coronary artery stenosis severity and coronary risk factors were assessed using univariate and multivariate analyses. Results: In stenotic regions, MFR correlated inversely with coronary artery stenosis severity (r=-0.50, p < 0.01). Univariate analysis did not show any significant difference in MFR between the patients with and the patients without each risk factor. In remote regions, however, MFR was significantly decreased in the diabetes and smoking groups (each p < 0.05). By multivariate analysis, diabetes and smoking were independent predictors of MFR (each p < 0.05). In the group with more than one risk factor, MFR was significantly lower (2.78 +/- 0.79) than in the other group (3.40 +/- 1.22, p < 0.05). Conclusion: MFR is influenced not only by coronary stenosis severity but also by coronary risk factors. In particular, the influence of risk factors should be considered in regions without severe coronary stenosis.
  • H Kageyama, K Morita, C Katoh, T Tsukamoto, K Noriyasu, M Mabuchi, M Naya, Y Kawai, N Tamaki
    EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 33 (1) 6 - 12 1619-7070 2006/01 [Refereed][Not invited]
     
    Purpose: Long-chain fatty acid (LCFA) is the main energy source for normal myocardium at rest, but in ischemic myocardium, the main energy substrate shifts from LCFA to glucose. I-123\-BMIPP is a radiolabeled LCFA analog. In chronic stable angina without previous infarction, we suppose that reduced I-123\-BMIPP uptake is related to the substrate shift in myocardium with decreased myocardial flow reserve (MFR). The purpose of this study was to relate I-123-BMIPP uptake to rest myocardial blood flow (MBF), hyperemic MBF, and MFR assessed with O-15-water positron emission tomography ( PET). Methods: We enrolled 21 patients with chronic stable angina without previous infarction, all of whom underwent I-123-BMIPP single-photon emission computed tomography (SPECT) and O-15-water PET. The left ventricle was divided into 13 segments. In each segment, rest MBF and hyperemic MBF were measured by PET. I-123-BMIPP uptake was evaluated as follows: score 0= normal, 1= slightly decreased uptake, 2= moderately decreased uptake, 3= severely decreased uptake, and 4= complete defect. I-123\-BMIPP uptake was compared with rest MBF, hyperemic MBF, and MFR. Results: The numbers of segments with I-123-BMIPP scores 0, 1, 2, 3, and 4 were 178, 40, 25, 24, and 0, respectively. The rest MBFs for scores 0, 1, 2, and 3 were 0.93 +/- 0.25, 0.86 +/- 0.21, 0.97 +/- 0.30, and 0.99 +/- 0.37 ml/min/g, respectively. The hyperemic MBFs for scores 0, 1, 2, and 3 were 2.76 +/- 1.29, 1.84 +/- 0.74, 1.37 +/- 0.39, and 1.08 +/-= 0.40 ml/min/g, respectively. The MFRs for scores 0, 1, 2, and 3 were 3.01 +/- 1.38, 2.20 +/- 0.95, 1.44 +/- 0.22, and 1.10 +/- 0.26, respectively. As I-123-BMIPP uptake declined, hyperemic MBF and MFR decreased. Conclusion: In chronic stable angina without previous infarction, reduced I-123-BMIPP uptake implies decreased MFR.

Books etc

  • 納谷昌直 (Contributor心臓SPECTとPET)
    日本臨牀社 2018/12
  • Coronary Intervention
    納谷昌直 (Contributor負荷心筋シンチグラフィ)
    2018/09
  • Diabetes Frontier
    納谷昌直 (Contributor心臓MRIによる心筋虚血と冠微小循環障害評価)
    2017/10
  • Nuclear Cardiac Imaging 5th Edition
    Masanao Naya (Contributor)
    2015
  • 日本心臓核医学会誌
    納谷昌直 (Contributor虚血性心疾患における心臓PETで測定した冠血流予備能による心血管リスク評価)
    2014
  • Heart View
    納谷昌直 (ContributorPETから診る;心筋症の診断におけるPETの有用性について)
    2013/03
  • 心不全
    納谷昌直 (Contributor核医学)
    2010
  • 虚血性心疾患の画像診断
    納谷昌直 (Contributor)
    2009

Conference Activities & Talks

  • PET perfusion  [Not invited]
    納谷昌直
    POPAI 2018 シンポジウム  2018/10
  • PET  [Not invited]
    納谷昌直
    Friends Live 2018 Lecture  2018/03
  • PET (SPECT)による虚血評価  [Not invited]
    納谷昌直
    第80回日本循環器学会学術集会 教育講演  2016/03
  • 18F-FDG PETおよび血流SPECTによる心サルコイドーシスの診断および重症度評価  [Not invited]
    納谷昌直
    第37回心筋生検研究会 シンポジウム  2015/12
  • 高リスク冠動脈疾患患者で冠血流予備能の高度低下例における冠血行再建術の予後改善効果.  [Not invited]
    納谷昌直
    第25回日本心臓核医学会学術集会 シンポジウム  2015/09
  • 18F -FDG and Perfusion PET for the Assessment of Disease Activity in Patients with Suspected Cardiac Sarcoidosis  [Not invited]
    納谷昌直
    第79回日本循環器学会学術集会 ワークショップ  2015/03
  • PETで測定した心筋血流量定量化の臨床応用  [Not invited]
    納谷昌直
    第19回日本心不全学会学術集会 教育講演  2015
  • 重症冠動脈病変の除外診断におけるルビジウム-82 PETを用いた冠血流予備能測定の有用性  [Not invited]
    納谷昌直
    第24回日本心臓核医学会学術集会 シンポジウム  2014/06
  • 心サルコイドーシスの重症度評価および予後予測におけるFDG-PETの有用性  [Not invited]
    納谷昌直
    第61回日本心臓病学会学術集会 ワークショップ  2013/09
  • 虚血性心疾患における心臓PETで測定した冠血流予備能による心血管リスク評価  [Not invited]
    納谷昌直
    第23回心臓核医学会学術総会 学会賞  2013/06
  • 心臓PETによる包括的多枝冠動脈病変の検出  [Not invited]
    納谷昌直
    第60回日本心臓病学会学術集会 ワークショップ  2012/09
  • C11-CGP-12177 PETによる心筋β受容体イメージング  [Not invited]
    納谷昌直
    第54回日本心臓病学会学術集会 シンポジウム  2012
  • Effect of angiotensin type 1 receptor blockade on coronary vasomotion assessed by 15O-water PET in patients with hypertension  [Not invited]
    Masanao Naya
    53th Annual Meeting of the Society of Nuclear Medicine YIA Symposium  2006/06
  • Determinations of coronary endothelial dysfunction in hypertensive patients  [Not invited]
    Masanao Naya
    53th Annual Meeting of the Society of Nuclear Medicine YIA Symposium  2006/06
  • Quantitative assessment of coronary endothelial function using PET and effects of angiotensin receptor blockade therapy in patients with hypertension  [Not invited]
    納谷昌直
    第70回日本循環器学会学術集会 シンポジウム  2006/03

MISC

Awards & Honors

  • 2018/09 三井生命厚生財団第51回医学研究助成
     
    受賞者: 納谷昌直
  • 2014/11 武田財団科学振興財団医学系研究奨励賞
     
    受賞者: 納谷昌直
  • 2014/01 Society of Cardiovascular Computed Tomography Best Abstract Award
     
    受賞者: Masanao Naya
  • 2013/06 The Japanese Society of Nuclear Cardiology Prize of The Japanese Society of Nuclear Cardiology
     
    受賞者: Masanao Naya
  • 2012/12 高血圧と冠動脈疾患研究会優秀奨励賞
     
    受賞者: 納谷昌直
  • 2012/08 第7回Vascular Biology Innovation研究奨励賞
     
    受賞者: 納谷昌直
  • 2012/03 第31回高桑榮松奨学基金奨励賞
     
    受賞者: 納谷昌直
  • 2012 Banyu Foundation Research
     
    受賞者: 納谷昌直
  • 2011/10 第22回伊藤記念研究助成
     
    受賞者: 納谷昌直
  • 2011/02 平成22年度フラテ研究奨励賞
     
    受賞者: 納谷昌直
  • 2009/06 The Japanese Society of Nuclear Cardiology Young investigator award
     
    受賞者: Masanao Naya
  • 2009/03 Society of Nuclear Medicine Wagner-Torizuka Fellowship
     
    受賞者: Masanao Naya
  • 2006/06 Society of Nuclear Medicine Young investigator award
     Effect of angiotensin type 1 receptor blockade on coronary endothelial function assessed by 15O-water PET in patients with hypertension 
    受賞者: Masanao Naya

Research Grants & Projects

  • 高分解能PET装置を用いた冠動脈プラーク炎症病変の可視化と心筋梗塞発症の機序解明
    科研費 基盤研究(B):
    Date (from‐to) : 2019/04 -2022/03 
    Author : 納谷昌直
  • PET,CT,MRIによる包括的映像法を用いた不安定プラークの病態評価
    科研費 基盤研究(B):
    Date (from‐to) : 2018/04 -2021/03 
    Author : 玉木長良
  • 左室駆出率の保たれた心不全患者における心筋線維化、左室拡張機能、運動耐容能の関連
    科研費 基盤研究(C):
    Date (from‐to) : 2018/04 -2021/03 
    Author : 岩野弘幸
  • PET用低酸素イメージング薬剤であるFMISOを用いた心サルコイドーシスの評価
    科研費 基盤研究(C):
    Date (from‐to) : 2017/04 -2020/03 
    Author : 真鍋治
  • 経皮的冠動脈形成術および冠動脈バイパス術の冠血流予備能に対する効果の検討
    科研費 基盤研究(C):
    Date (from‐to) : 2016/04 -2019/03 
    Author : 納谷昌直
  • PETによる心血管疾患の活動性の映像化と治療戦略への応用
    科研費 基盤研究(B):
    Date (from‐to) : 2015/04 -2018/03 
    Author : 玉木長良
  • PET-MRI融合画像を用いた心サルコイドーシスの不整脈の病態評価
    科研費 挑戦的萌芽研究:
    Date (from‐to) : 2015/04 -2017/03 
    Author : 玉木長良
  • 320列MDCTによる包括的冠動脈形態および機能的狭窄度評価法の確立
    科研費 基盤研究(C):
    Date (from‐to) : 2014/04 -2017/03 
    Author : 真鍋徳子
  • 心筋血流予備能を用いた拡張障害心不全患者における包括的リスク評価
    科研費 基盤研究(C):
    Date (from‐to) : 2012/04 -2016/03 
    Author : 納谷昌直
  • メタボリックシンドロームにおける冠血管内皮機能障害の評価と有効な治療法の確立
    科研費 若手研究(B):
    Date (from‐to) : 2008/04 -2010/03 
    Author : 納谷昌直

Educational Activities

Teaching Experience

  • 医学総論
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学研究科
  • Basic Principles of Medicine
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 虚血性心疾患・心不全・高血圧・不整脈 Ischemic heart disease, Heart failure, Hypertension, Arrhythmia
  • Master's Thesis Research in Medical Sciences
    開講年度 : 2018
    課程区分 : 修士課程
    開講学部 : 医学院
    キーワード : 虚血性心疾患・心不全・高血圧・不整脈 Ischemic heart disease, Heart failure, Hypertension, Arrhythmia
  • Principles of Medicine
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 虚血性心疾患・心不全・高血圧・不整脈 Ischemic heart disease, Heart failure, Hypertension, Arrhythmia
  • Dissertation Research in Medical Sciences
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 虚血性心疾患・心不全・高血圧・不整脈 Ischemic heart disease, Heart failure, Hypertension, Arrhythmia
  • Dissertation Research in Clinical Medicine
    開講年度 : 2018
    課程区分 : 博士後期課程
    開講学部 : 医学院
    キーワード : 虚血性心疾患・心不全・高血圧・不整脈 Ischemic heart disease, Heart failure, Hypertension, Arrhythmia


Copyright © MEDIA FUSION Co.,Ltd. All rights reserved.