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| 1.
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Goto, Yoshikazu ; Funada, Akira ; Goto, Yumiko ; 後藤, 由和 ; 舟田, 晃
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金沢大学医薬保健研究域医学系<br />Embargo Periods 12 Months
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Funada, Akira ; Konno, Tetsuo ; Fujino, Noboru ; Muramoto, Akihiko ; Hayashi, Kenshi ; Tsubokawa, Toshinari ; Sakata, Kenji ; Kawashiri, Masa-aki ; Takeda, Yoshiyu ; Ino, Hidekazu ; Yamagishi, Masakazu ; 舟田, 晃 ; 今野, 哲雄 ; 藤野, 陽 ; 林, 研至 ; 坂田, 憲治 ; 川尻, 剛照 ; 武田, 仁勇 ; 井野, 秀一 ; 山岸, 正和
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金沢大学医薬保健研究域医学系<br />Background: Although the renin - angiotensin system (RAS) can affect the development of left ventric
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ular (LV) hypertrophy, few data exist regarding the relationships between RAS polymorphisms and alteration of LV function. The effect of RAS polymorphisms on LV function in genotyped hypertrophic cardiomyopathy (HCM) was examined in the present study. Methods and Results: The study group comprised 126 carriers with sarcomere gene mutations from 49 HCM families (64 males, mean age 51±21 years). LV morphology and function were evaluated by echocardiography. In angiotensin-converting enzyme (ACE) insertion/deletion (I/D), the D allele (n=81) exhibited significantly larger LV end-systolic dimension (LVDs) (32±11 mm) and lower ejection fraction (56±15%) than those with the II genotype (28±7 mm and 62±12%, respectively, P<0.05; n=45). Although angiotensin II type 1 receptor (AT1-R) A/C1166 polymorphism did not affect echocardiographic parameters, the presence of the ACE D allele with the AT1-R C1166 allele (n=9) was associated with larger LVDs (37±17 mm) and lower ejection fraction (48±20%) compared with other genotypes (30±9 mm and 58±14%, respectively, P<0.05; n=117). Under these conditions, severe LV hypertrophy was frequently associated with LV wall thinning. Conclusions: The presence of both the ACE D and AT1-R C1166 allele is associated with LV dilation with systolic dysfunction in genotyped HCM. In addition to the severity of LV hypertrophy, screening for these RAS polymorphisms could contribute to further risk stratification of patients with HCM, although other genetic polymorphisms should be further examined.<br />出版者照会後に全文公開
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Shimizu, Masami ; Ino, Hidekazu ; Yasuda, Toshihiko ; Fujino, Noboru ; Uchiyama, Katsuharu ; Mabuchi, Tomohito ; Konno, Tetsuo ; Kaneda, Tomoya ; Fujita, Takashi ; Masuta, Eiichi ; Kato, Masahiro ; Funada, Akira ; Mabuchi, Hiroshi
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金沢大学大学院医学系研究科 <br />Background: Some patients with dilated cardiomyopathy (DCM) have mutations of the genes that encode
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sarcomeric or cytoskeletal proteins of cardiomyocytes, but the prevalence of these mutations in Japan remains unclear. Methods and Results: A group of 99 unrelated adult patients with DCM (familial n=27, sporadic n=72) were screened for the following genes: cardiac ﾎｲ-myosin heavy chain, cardiac myosin-binding protein C (MYBPC3), regulatory and essential myosin light chains, a cardiac actin, ﾎｱ tropomyosin, cardiac troponin T, cardiac troponin I, cardiac troponin C, dystrophin, and lamin A/C. A mutation (R820Q) in MYBPC3 was found in an aged patient. In addition, dystrophin mutations were identified in 3 male patients (2 with exon 45-48 deletion and 1 with exon 48-52 deletion). The prevalence of dystrophin mutations in male patients with DCM was 4.4% (3 of 68). No mutations involving amino acid changes were identified in the other genes. Conclusions: Although cases of adult patients with DCM caused by mutations of the genes encoding sarcomeric or cytoskeletal proteins of cardiomyocytes are infrequent in Japan, it may be advisable to screen older DCM patients for MYBPC3 mutations, and male patients with familial DCM for dystrophin mutations.
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Inoue, Masaru ; Shimizu, Masami ; Ino, Hidekazu ; Yamaguchi, Masato ; Terai, Hidenobu ; Fujino, Noboru ; Sakata, Kenji ; Funada, Akira ; Tatami, Ryozo ; Ishise, Shozo ; Kanaya, Hounin ; Mabuchi, Hiroshi
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金沢大学大学院医学系研究科 <br />Background: There has not been a comparison of the electrocardiographic (ECG) finding of ST-segment
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elevation in the precordial leads in patients with takotsubo cardiomyopathy (TC) and those with anterior acute myocardial infarction (AMI), with regard to the location of the culprit lesion. Methods and Results: The present study evaluated 18 patients with TC, and 85 with anterior AMI who were divided into 3 groups: group A had the culprit lesion proximal to both the first septal branch (S1) and the first diagonal branch (D1), group B had the culprit lesion proximal to either S1 or D1, and group C had the culprit lesion distal to both S1 and D1. In patients with TC, reciprocal ST-segment depression in the inferior leads was observed less frequently than in patients in groups A (p<0.0001) and B (p=0.0002), and abnormal Q waves and ST-segment elevation in the inferior leads were observed more frequently than in group A (p=0.0007, p=0.0057, respectively). The ECG findings in TC did not differ from those in group C. Conclusion: Electrocardiographic findings may differentiate TC from AMI with a proximal lesion of left anterior descending coronary artery, but not those with distal lesions.
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Funada, Akira ; Masuta, Eiichi ; Fujino, Noboru ; Hayashi, Kenshi ; Ino, Hidekazu ; Kita, Yoshihito ; Ikeda, Hiroko ; Fujii, Takahiko ; Nakanuma, Yasuni ; Yamagishi, Masakazu
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Hypertrophic cardiomyopathy (HCM) is associated with gene mutations that encode sarcomeric proteins. However, the relationship between genotype and histopathologic fndings is unclear. We report on two autopsy cases with advanced
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HCM associated with deletion of lysine 183 mutation in the cardiac troponin I gene. One case, a 74-year-old female exhibited dilated cardiomyopathy-like features. Transmural scarring was diffuse and circumferential, involving the whole left ventricle, especially the ventricular septum which was replaced with extensive fbrosis and showed marked wall thinning. The other case, a 92-year-old male revealed typical HCM fndings. Patchy scars which corresponded to replacement fbrosis were found extending from the septum to the anterior wall. These two autopsy cases indicate the clinical heterogeneity of HCM even within the same disease-causing mutation and suggest that the degree and extent of fbrosis determine differences in the clinical manifestations of HCM. This is the frst autopsy report that demonstrates identical sarcomeric gene mutations causing different clinical manifestations and histologic fndings. The fndings suggest that additional genetic or environmental factors infuence the phenotypic expressions and clinical courses of HCM caused by genetic mutation of sarcomeric proteins.
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Goto, Yoshikazu ; Funada, Akira ; Nakatsu-Goto, Yumiko
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Introduction: Obtaining favorable neurological outcomes is extremely difficult in children transported to a hospital wit
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hout a prehospital return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA). However, the crucial prehospital factors affecting outcomes in this cohort remain unclear. We aimed to determine the prehospital factors for survival with favorable neurological outcomes (Cerebral Performance Category 1 or 2 (CPC 1-2)) in children without a prehospital ROSC after OHCA. Methods: Of 9093 OHCA children, 7332 children (age <18years) without a prehospital ROSC after attempting resuscitation were eligible for enrollment. Data were obtained from a prospectively recorded Japanese national Utstein-style database from 2008 to 2012. The primary endpoint was 1-month CPC 1-2 after OHCA. Results: The 1-month survival and 1-month CPC 1-2 rates were 6.92% (n=508) and 0.99% (n=73), respectively. The proportions of the following prehospital variables were significantly higher in the 1-month CPC 1-2 cohort than in the 1-month CPC 3-5 cohort: age (median, 3years (interquartile range (IQR), 0-14) versus 1year (IQR, 0-11), p<0.05), bystander-witnessed arrest (52/73 (71.2%) versus 1830/7259 (25.2%), p<0.001), initial ventricular fibrillation (VF)/pulseless ventricular tachycardia (VT) rhythm (28/73 (38.3%) versus 241/7259 (3.3%), p<0.001), presumed cardiac causes (42/73 (57.5%) versus 2385/7259 (32.8%), p<0.001), and actual shock delivery (25/73 (34.2%) versus 314/7259 (4.3%), p<0.0001). Multivariate logistic regression analysis indicated that 2 prehospital factors were associated with 1-month CPC 1-2: initial non-asystole rhythm (VF/pulseless VT: adjusted odds ratio ( aOR), 16.0; 95% confidence interval (CI), 8.05-32.0; pulseless electrical activity (PEA): aOR, 5.19; 95% CI, 2.77-9.82) and bystander-witnessed arrest (aOR, 3.22; 95% CI, 1.84-5.79). The rate of 1-month CPC 1-2 in witnessed-arrest children with an initial VF/pulseless VT was significantly higher than that in those with other initial cardiac rhythms (15.6% versus 2.3% for PEA and 1.2% for asystole, p for trend<0.001). Conclusions: The crucial prehospital factors for 1-month survival with favorable neurological outcomes after OHCA were initial non-asystole rhythm and bystander-witnessed arrest in children transported to hospitals without a prehospital ROSC. © 2015 Goto et al.
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Nishi, Taiki ; Kamikura, Takahisa ; Funada, Akira ; Myojo, Yasuhiro ; Ishida, Tetsuya ; Inaba, Hideo
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Aim: Dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) impacts the rates of bystander CPR (BCPR) and survival a
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fter out-of-hospital cardiac arrests (OHCAs). This study aimed to elucidate whether regional variations in indexes for BCPR and emergency medical service (EMS) may be associated with OHCA outcomes. Methods: We conducted a population-based observational study involving 157,093 bystander-witnessed, resuscitation-attempted OHCAs without physician involvement between 2007 and 2011. For each index of BCPR and EMS, we classified the 47 prefectures into the following three groups: advanced, intermediate, and developing regions. Nominal logit analysis followed by multivariable logistic regression including OHCA backgrounds was employed to examine the association between neurologically favourable 1-month survival, and regional classifications based on BCPR- and EMS-related indexes. Results: Logit analysis including all regional classifications revealed that the number of BLS training course participants per population or bystander's own performance of BCPR without DA-CPR was not associated with the survival. Multivariable logistic regression including the OHCA backgrounds known to be associated with survival (BCPR provision, arrest aetiology, initial rhythm, patient age, time intervals of witness-to-call and call-to-arrival at patient), the following regional classifications based on DA-CPR but not on EMS were associated with survival: sensitivity of DA-CPR [adjusted odds ratio (95% confidence intervals) for advanced region; those for intermediate region, with developing region as reference, 1.277 (1.131-1.441); 1.162 (1.058-1.277)]; the proportion of bystanders to follow DA-CPR [1.749 (1.554-1.967); 1.280 (1.188-1.380)]. Conclusions: Good outcomes of bystander-witnessed OHCAs correlate with regions having higher sensitivity of DA-CPR and larger proportion of bystanders to follow DA-CPR. © 2015 Elsevier Ireland Ltd.<br />Embargo Period 12 months
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| 8.
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Funada, Akira ; Goto, Yoshikazu ; Tada, Hayato ; Teramoto, Ryota ; Shimojima, Masaya ; Hayashi, Kenshi ; Yamagishi, Masakazu ; 舟田 , 晃 ; 後藤, 由和 ; 多田, 隼人 ; 寺本, 了太 ; 下島, 正也 ; 林, 研至 ; 山岸, 正和
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Background:The appropriate duration of prehospital cardiopulmonary resuscitation (CPR)administered by emergency medical
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service (EMS) providers for patients with out-of-hospital cardiac arrest (OHCA) necessary to achieve 1-month survival with favorable neurological outcome (Cerebral Performance Category 1 or 2, CPC 1–2) is unclear and could differ by age. Methods and Results:We analyzed the records of 35,709 adult OHCA patients with return of spontaneous circulation (ROSC) before hospital arrival in a prospectively recorded Japanese registry between 2011 and 2014. The CPR duration was defined as the time from CPR initiation by EMS providers to prehospital ROSC. The rate of 1-month CPC 1–2 was 21.4% (7,650/35,709). The CPR duration was independently and inversely associated with 1-month CPC 1–2 (adjusted odds ratio, 0.93 per 1-min increment; 95% confidence interval, 0.93–0.94). The CPR duration increased with age (P<0.001). However, the CPR duration beyond which the proportion of OHCA patients with 1-month CPC 1–2 decreased to <1% declined with age: 28 min for patients aged 18–64 years, 25 min for 65–74 years, 23 min for 75–84 years, 20 min for 85–94 years, and 18 min for ≥95 years. Conclusions:In patients who achieved prehospital ROSC after OHCA, the duration of CPR administered by EMS providers necessary to achieve 1-month CPC 1–2 varied by age.<br />出版者照会後に全文公開
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| 9.
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Funada, Akira ; Goto, Yoshikazu ; Maeda, Tetsuo ; Teramoto, Ryota ; Hayashi, Kenshi ; Yamagishi, Masakazu
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Background:There is sparse data regarding the survival and neurological outcome of elderly patients with out-of-hospital
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cardiac arrest (OHCA).Methods and Results:OHCA patients (334,730) aged ≥75 years were analyzed using a nationwide, prospective, population-based Japanese OHCA database from 2008 to 2012. The overall 1-month survival with favorable neurological outcome (Cerebral Performance Category Scale, category 1 or 2; CPC 1-2) rate was 0.88%. During the study period, the annual 1-month CPC 1-2 rate in whole OHCA significantly improved (0.73% to 0.96%, P for trend <0.001). In particular, outcomes of OHCA patients aged 75 to 84 years and those aged 85 to 94 years significantly improved (0.98% to 1.28%, P for trend=0.01; 0.46% to 0.70%, P for trend <0.001, respectively). However, in OHCA patients aged ≥95 years, the outcomes did not improve. Multivariate logistic regression analysis indicated that younger age, shockable first documented rhythm, witnessed arrest, earlier emergency medical service (EMS) response time, and cardiac etiology were significantly associated with the 1-month CPC 1-2. Under these conditions, elderly OHCA patients who had cardiac etiology, shockable rhythm and had a witnessed arrest had acceptable 1-month CPC1-2 rate; 7.98% in cases where OHCA was witnessed by family, 15.2% by non-family, and 25.6% by EMS.Conclusions:The annual 1-month CPC 1-2 rate after OHCA among elderly patients significantly improved, and the resuscitation of elderly patients in a selected population is not futile.
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舟田, 晃 ; Funada, Akira
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消防庁の院外心停止全国前向き全例登録を用いて、高齢院外心停止の神経学的転帰を検討した。65-74、75-89歳の神経学的転帰良好の割合は年々改善傾向にあったが、90歳以上では改善を認めなかった。神経学的転帰良好に関連のある因子として、初期波
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形種別、目撃の有無、年齢を同定し、『院外心停止後神経学的転帰良好予測率層別化モデル』を作成した。初期波形が除細動非適応波形で目撃がない場合には、1ヶ月後の神経学的転帰良好は1%未満と予測され、特に高齢者において蘇生処置の差し控えを検討する根拠となると考えられた。一方で、神経学的転帰良好の割合は年々改善しており、適宜、モデルのアップデートが必要と考えられた。<br />Using Japanese nationwide out-of-hospital cardiac arrest (OHCA) registry, we analyzed the rate and trend of neurologically intact survival in elderly patients with OHCA. The rate of neurologically intact survival significantly improved in patients aged 65-74 and 75-89 years. However, in patients aged 90 years or over, no improvement was observed. We developed a prediction chart using variables significantly associated with increased chances of neurologically intact survival, such as initial documented rhythm, witnessed status, and age, to estimate the neurologically intact survival rate after OHCA. The estimated neurologically intact survival rate in patients with unwitnessed OHCA with a non-shockable rhythm was <1% in all age groups. Particularly, in elderly patients with OHCA, this information can help in deciding whether to withhold or terminate resuscitation efforts. However, as the neurologically intact survival rate has improved annually, the prediction chart needs to be updated.<br />研究課題/領域番号:16K19171, 研究期間(年度):2016-04-01 - 2019-03-31<br />出典：「高齢院外心肺停止傷病者における心肺蘇生および予後に関する研究」研究成果報告書 課題番号16K19171（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-16K19171/16K19171seika/）を加工して作成
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