著者

Kyohei Marume Seiji Takashio Masato Nishi Kyoko Hirakawa Masahiro Yamamoto Shinsuke Hanatani Seitaro Oda Daisuke Utsunomiya Shinya Shiraishi Mitsuharu Ueda Taro Yamashita Kenji Sakamoto Eiichiro Yamamoto Koichi Kaikita Yasuhiro Izumiya Yasuyuki Yamashita Yukio Ando Kenichi Tsujita

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.83, no.8, pp.1698-1708, 2019-07-25 (Released:2019-07-25)

参考文献数

30

被引用文献数

31

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Background:A recent study revealed a high prevalence of transthyretin (TTR) cardiac amyloidosis (CA) in elderly patients. 99 mTc-labeled pyrophosphate (99 mTc-PYP) scintigraphy is a remarkably sensitive and specific modality for TTR-CA, but is only available in specialist centres; thus, it is important to raise the pretest probability. The aim of this study was to evaluate the characteristics of patients with 99 mTc-PYP positivity and make recommendations about patient selection for 99 mTc-PYP scintigraphy.Methods and Results:We examined 181 consecutive patients aged ≥70 years who underwent 99 mTc-PYP scintigraphy at Kumamoto University Hospital between January 2012 and December 2018. Logistic regression analyses showed that high-sensitivity cardiac troponin T (hs-cTnT) ≥0.0308 ng/mL, left ventricular posterior wall thickness ≥13.6 mm, and wide QRS (QRS ≥120 ms) were strongly associated with 99 mTc-PYP positivity. We developed a new index for predicting 99 mTc-PYP positivity by adding 1 point for each of the 3 factors. The 99 mTc-PYP positive rate increased by a factor of 4.57 for each 1-point increase (P<0.001). Zero points corresponded to a negative predictive value of 87% and 3 points corresponded to a positive predictive value of 96% for 99 mTc-PYP positivity.Conclusions:The combination of biochemical (hs-cTnT), physiological (wide QRS), and structural (left ventricular posterior wall thickness) findings can raise the pretest probability for 99 mTc-PYP scintigraphy. It can assist clinicians in determining management strategies for elderly patients with suspected CA.

著者

Yasuaki Okuda Toshiyuki Yamada Mitsuharu Ueda Yukio Ando

出版者

The Japanese Society of Internal Medicine

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

vol.57, no.23, pp.3351-3355, 2018-12-01 (Released:2018-12-01)

参考文献数

11

被引用文献数

33 34

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Objective To clarify the underlying diseases, clinical manifestations, and treatment strategies for Amyloid A (AA) amyloidosis (AAA) in Japanese patients. Methods We conducted a survey on Japanese patients with AAA treated between January 1, 2012, and December 31, 2014. Results A total of 199 patients with AAA were included in the present study. The underlying diseases of AAA were rheumatoid arthritis (60.3%), uncharacterized inflammatory disorders (11.1%), neoplasms (7.0%), other rheumatic diseases (6.5%), inflammatory bowel diseases (4.5%), chronic infection (4.5%), Castleman's disease (4.0%), and autoinflammatory diseases (2.0%). The clinical manifestations at the diagnosis of AAA were moderate to severe renal dysfunction (46.2%), moderate to severe proteinuria (30.7%), intractable diarrhea (32.2%), melena (4.5%), paralytic ileus (3.5%), heart failure (11.6%), cardiac conduction disturbances (10.1%), arrhythmia (5.5%), and hypothyroidism (11.6%). Diagnostic biopsies were performed most frequently in the gastrointestinal tract (66.3%), followed by the kidneys (22.1%), heart (5.5%), abdominal fat (4.0%), and others (3.0%). Biologics were used to treat 97 patients with AAA (48.7%). Tocilizumab (TCZ) was administered to 66 patients, with 95.5% showing good responses. Anti-TNF agents were administered to 27 patients, with 74.1% showing good responses. The treatment effects of TCZ were significantly superior to those of anti-TNF agents (p<0.007). Conclusion The most common underlying diseases of AAA were rheumatic diseases. Uncharacterized inflammatory disorders and neoplasms were also frequently observed in patients with AAA. Renal and gastrointestinal manifestations were common and important for the diagnosis of AAA, with cardiac manifestations also being of significance. Biologics, particularly TCZ, were effective therapeutic modalities.

著者

Koji Sato Kenji Sakamoto Yoichiro Hashimoto Kazuhiko Hanzawa Daisuke Sueta Sunao Kojima Masaya Fukuda Hiroki Usuku Fumie Kihara Hiroshi Hosokawa Yohei Nagai Makoto Nakajima Yoshiharu Saito Kayoko Sakai Sumio Masunaga Shinji Tanaka Kazuteru Fujimoto Kenji Morihisa Katsuo Noda Kazuhiro Nishigami Kohei Nagata Koichiro Fujisue Noriaki Tabata Yukio Ando Kenichi Tsujita Hisao Ogawa Seiji Hokimoto on behalf of the KEEP Project

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-18-1369, (Released:2019-04-06)

参考文献数

22

被引用文献数

26

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Background: After previous earthquakes, a high prevalence of deep vein thrombosis (DVT) has been reported. We examined DVT prevalence and risk factors in evacuees of the Kumamoto earthquakes by performing mobile DVT screening at various evacuation centers around the epicenter. Methods and Results: For 1 month after the Kumamoto earthquake on 14 April 2016, mobile DVT screening using portable ultrasonography (US) was performed at 80 evacuation centers. Questionnaires, physical examination, and US of the lower limb were carried out, and simple D-dimer measurements were undertaken for DVT-positive examinees. The total number of examinees was 1,673, of whom 178 (10.6%) had DVT. The prevalence of DVT seemed to be gradually decreasing in the screening period, but age, use of sleep medication, prevalence of hypertension, dyslipidemia, leg edema, and lower leg varix were significantly higher in the DVT positive group than in the negative group. On multivariable logistic regression analysis, high age (≥70 years old), use of sleep medication, lower leg edema, and lower leg varix were significant predictors of DVT. In examinees with these 4 predictors, the DVT positive rate was 71.4%. Conclusions: In the first month after the Kumamoto earthquakes, DVT prevalence and severity, evaluated on D-dimer level, decreased with the passage of time. Mobile DVT screening indicated significant factors stratifying DVT risk in the evacuees.

著者

Masamichi Inoue Kyosuke Muta Ahmed Fouad Abdelwahab Mohammed Risako Onodera Taishi Higashi Kenta Ouchi Mitsuharu Ueda Yukio Ando Hidetoshi Arima Hirofumi Jono Keiichi Motoyama

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.45, no.11, pp.1660-1668, 2022-11-01 (Released:2022-11-01)

参考文献数

37

被引用文献数

4

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Hereditary amyloidgenic transthyretin (ATTR) amyloidosis is caused by a genetic point-mutated transthyretin such as TTR Val30Met (TTR V30M), since it forms protein aggregates called amyloid resulting in the tissue accumulation and functional disorders. In particular, ATTR produced by retinal pigment epithelial cells often causes ATTR ocular amyloidosis, which elicits deterioration of ocular function and ultimately blindness. Therefore, development of novel therapeutic agents is urgently needed. Genome-editing technology using Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated proteins (CRISPR-Cas9) system is expected to be a therapeutic approach to treat genetic diseases, such as ATTR amyloidosis caused by a point mutation in TTR gene. Previously, we reported that glucuronylglucosyl-β-cyclodextrin conjugated with a polyamidoamine dendrimer (CDE) had excellent gene transfer ability and that underlying dendrimer inhibited TTR aggregation. Conversely, folate receptors are known to be highly expressed in retina; thus, folate has potential as a retinal target ligand. In this study, we prepared a novel folate-modified CDE (FP-CDE) and investigated its potential as a carrier for the retinal delivery of TTR-CRISPR plasmid DNA (pDNA). The results suggested that FP-CDE/TTR-CRISPR pDNA could be taken up by retinal pigment epithelial cells via folate receptors, exhibited TTR V30M amyloid inhibitory effect, and suppressed TTR production via the genome editing effect (knockout of TTR gene). Thus, FP-CDE may be useful as a novel therapeutic TTR-CRISPR pDNA carrier in the treatment of ATTR ocular amyloidosis.

著者

Hiroki Usuku Eiichiro Yamamoto Masato Nishi Takashi Komorita Masafumi Takae Taiki Nishihara Fumi Oike Masanobu Ishii Koichiro Fujisue Daisuke Sueta Satoshi Araki Seiji Takashio Seitaro Oda Yohei Misumi Mitsuharu Ueda Taishi Nakamura Hiroaki Kawano Hirofumi Soejima Kenji Sakamoto Koichi Kaikita Yukio Ando Hirotaka Matsui Kenichi Tsujita

出版者

The Japanese Circulation Society

雑誌

Circulation Reports (ISSN:24340790)

巻号頁・発行日

vol.2, no.12, pp.730-738, 2020-12-10 (Released:2020-12-10)

参考文献数

27

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Background:Using transthoracic echocardiography, including 2D speckle tracking imaging (STI), this study examined cardiac function after domino liver transplantation (DLT) with liver grafts explanted from patients with hereditary amyloidogenic transthyretin amyloidosis.Methods and Results:In all, 14 patients who underwent DLT at Kumamoto University Hospital and for whom 2D STI information was available were enrolled in the study; time-dependent echocardiographic changes were evaluated in 7. Although left ventricular (LV) systolic and diastolic function did not differ between the pre- and post-DLT periods (mean [±SD] 5.4±1.0 years after DLT), there were significant (P<0.05 for all) increases in the post- vs. pre-DLT period in basal longitudinal strain (LS; −13.4±2.3 vs. −19.3±4.4), relative apical LS index (=apical LS/[basal LS+mid LS]; 0.75±0.20 vs. 0.58±0.08), and LV ejection fraction/global LS (3.91±0.58 vs. 3.06±0.44). Age at the time of DLT was significantly higher in the group with impaired (>−14%) than preserved basal LS (57.2±3.5 vs. 39.6±16.0 years; P<0.05). When control subjects (n=14) were added to the enrolled DLT recipients, multivariable logistic regression analysis revealed that a history of DLT was significantly associated with impaired basal LS (>−14%; odds ratio 28.39, 95% confidence interval 1.89–427.45, P<0.05).Conclusions:LV systolic and diastolic function was preserved in the long term after DLT. However, 2D STI revealed subtle cardiac dysfunction in DLT recipients, which may be an early manifestation of cardiac amyloidosis.

著者

Jin Endo Motoaki Sano Yasuhiro Izumiya Kenichi Tsujita Kazufumi Nakamura Nobuhiro Tahara Koichiro Kuwahara Takayuki Inomata Mitsuharu Ueda Yoshiki Sekijima Yukio Ando Hiroyuki Tsutsui Mitsuaki Isobe Keiichi Fukuda

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-19-0811, (Released:2019-11-16)

参考文献数

4

被引用文献数

18

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Transthyretin cardiac amyloidosis is a progressive and life-threating disease that is significantly underdiagnosed, and the actual number of patients with the disease is presently unknown. Accumulation of wild-type transthyretin-derived amyloid in the heart is a common finding in very elderly patients. Recent clinical trials demonstrated that tafamidis reduced all-cause death and the number of cardiovascular hospitalizations when compared with placebo. The Japanese Ministry of Health, Labour and Welfare approved tafamidis (Vyndaqel®, Pfizer Inc.) for the treatment of cardiomyopathy caused by both wild-type and mutated transthyretin-derived amyloidoses. This scientific statement on transthyretin-derived cardiac amyloidosis summarizes the conditions for reimbursement of the cost of tafamidis therapy, and the institutional and physician requirements for the introduction of tafamidis.

著者

Taku Nakase Taro Yamashita Yoshimasa Matsuo Toshiya Nomura Keiko Sasada Teruaki Masuda Yohei Misumi Kotaro Takamatsu Seitaro Oda Yutaro Furukawa Konen Obayashi Hirotaka Matsui Yukio Ando Mitsuharu Ueda

出版者

The Japanese Society of Internal Medicine

雑誌

Internal Medicine (ISSN:09182918)

巻号頁・発行日

pp.2456-18, (Released:2019-06-07)

参考文献数

17

被引用文献数

3

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We report the clinical features of a patient with hereditary ATTR amyloidosis associated with a novel mutation (Y114S, p.Y134S). A 65-year-old Japanese man was admitted to our hospital after a 3-year history of progressive dyspnea on exertion. Five years previously, he presented dysesthesia in both hands caused by carpal tunnel syndrome. A genetic analysis revealed a base pair substitution of adenine to cytosine in the second codon of exon 4, residue 114, in the TTR gene (c.401A>C). The clinical characteristics were progressive cardiomyopathy with a poor vital prognosis, late onset, sporadic case, bilateral carpal tunnel syndrome, hypothyroidism, and small fiber neuropathy.