Details of a Researcher - SHIRAISHI Yasuyuki

Papers - SHIRAISHI Yasuyuki

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Clinical implications of the blood urea nitrogen/creatinine ratio in heart failure are and their association with haemoconcentration

Sujino Y., Nakano S., Tanno J., Shiraishi Y., Goda A., Mizuno A., Nagatomo Y., Kohno T., Muramatsu T., Nishimura S., Kohsaka S., Yoshikawa T.

ESC Heart Failure (ESC Heart Failure) 6 ( 6 ) 1274 - 1282 2019

© 2019 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology. Aims: The blood urea nitrogen (BUN)/creatinine ratio is a strong prognostic indicator in patients with acute decompensated heart failure (ADHF). However, the clinical impact of a high BUN/creatinine ratio at discharge with respect to renal dysfunction, neurohormonal hyperactivity, and different responsiveness to decongestion therapy remains unclear. Herein, we examined (i) the predictive value of a high BUN/creatinine ratio at discharge and (ii) its haemoconcentration-dependent effects, in patients with ADHF. Methods and results: The West Tokyo Heart Failure registry was a multicentre, prospective cohort registry-based study that enrolled patients hospitalized with a diagnosis of ADHF. The endpoint was post-discharge all-cause death. Based on the degree of haemoconcentration, patients (n = 2090) were divided into four subcategories. In multivariate proportional hazard analyses, a higher BUN/creatinine ratio was independently associated with higher all-cause mortality in the total population and in the extreme haemodilution (ΔHaemoglobin ≤ −0.9 g/dL) and haemoconcentration (0.8 g/dL ≤ ΔHaemoglobin) subcategories, but not in the modest haemodilution/haemoconcentration subcategories. Conclusions: A higher BUN/creatinine ratio at discharge was independently associated with higher post-discharge all-cause mortality in patients with ADHF. The predictive value of a high BUN/creatinine ratio at discharge was haemoconcentration dependent and may be an unfavourable predictor in patients showing excessive haemoconcentration and haemodilution, but not in those showing modest haemoconcentration/haemodilution.

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In-hospital outcome in patients presenting with acute coronary syndrome with left main coronary artery disease: A report from Japanese prospective multicenter percutaneous coronary intervention registry

Tani H., Sawano M., Numasawa Y., Kobayashi Y., Suzuki M., Noma S., Shiraishi Y., Ueda I., Fukuda K., Kohsaka S.

Journal of Cardiology (Journal of Cardiology) 75 ( 6 ) 635 - 640 2019

ISSN 09145087

© 2019 Japanese College of Cardiology Background: Patients presenting with acute coronary syndrome (ACS) from left main (LM) disease are at a high risk for mortality despite recent advancement in devices and techniques during percutaneous coronary interventions (PCI). We aimed to evaluate patient characteristics, clinical presentations, and key clinical characteristics associated with adverse in-hospital outcomes among ACS patients undergoing LM-PCI. Methods: We retrospectively identified 280 LM-ACS patients (3.7 %) from 7608 ACS patients in the prospective multicenter Japan Cardiovascular Database-Keio Inter-Hospital Cardiovascular Studies registry from March 2009 to May 2016 and divided them into those with/without PCI/coronary artery bypass grafting. We compared baseline demographics, coronary lesion characteristics, PCI details, and short-term outcomes, including in-hospital mortality and periprocedural complications, between the two groups. Results: Among LM-ACS patients, 38.6 % presented with ST elevation myocardial infarction, 29.6 % with cardiogenic shock (CS), and 15.4 % with cardiac arrest. The observed in-hospital mortality rate was 18.9 % with presence of CS [odds ratio (OR): 10.16, 95 % confidence interval (CI): 4.51–22.91, p < 0.001] and absence of prior revascularization (de novo patients; OR: 4.31, 95 % CI: 1.43–12.94, p = 0.009) was independently associated with higher incidence of in-hospital mortality. Notably, the observed mortality rate was substantially higher among de novo patients than the predicted mortality rate with a contemporary risk model (observed: 25.1 %; predicted: 11.6 %). Conclusions: Prior revascularization act as a protective factor among LM-ACS patients in the contemporary era of PCI. Further studies to detect those at higher risk for LM coronary lesion progression are needed to fully implement these findings into clinical practice.

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Staged transcatheter closure for atrial septal defect and patent ductus arteriosus: A case report

Soma Y., Shiraishi Y., Kanazawa H., Fukuda K.

European Heart Journal - Case Reports (European Heart Journal - Case Reports) 3 ( 2 ) 2019

Research paper (scientific journal), Corresponding author, Accepted

© The Author(s) 2019. Background Atrial septal defect (ASD) and patent ductus arteriosus (PDA) are both common congenital heart diseases, but the combination of these two cardiac defects is extremely rare, and the therapeutic strategy is controversial. Case summary We treated an adult patient with combined ASD and PDA, and safely attained a successful outcome with two-stage transcatheter closure, which is PDA closure preceding ASD closure, to prevent serious complications. Discussion Transcatheter closure of one of the defects is now widely accepted as an alternative to surgical closure. In addition, adults with both ASD and PDA are better suited for transcatheter closure than surgical closure. One of the reasons is the difficulty to ligate the ductus arteriosus of an adult patient due to its friability and calcification. Meanwhile, simultaneous combined transcatheter closure of ASD and PDA can result in serious complications, such as thrombocytopenia and haemolysis, whose mechanism is considered to be the destruction of platelets and red blood cells by the residual shunt through implanted devices. Additionally, antiplatelet therapy that prevents device-related thrombus formation after ASD closure can possibly exacerbate thrombocytopenia and haemolysis. Therefore, the staged strategy is reasonable from the perspectives of antiplatelet therapy and haemodynamic changes.

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Prognostic impact of previous hospitalization in acute heart failure patients

Akita K., Kohno T., Kohsaka S., Shiraishi Y., Nagatomo Y., Goda A., Mizuno A., Sujino Y., Fukuda K., Yoshikawa T.

Circulation Journal (Circulation Journal) 83 ( 6 ) 1261 - 1268 2019

ISSN 13469843

© 2019, Japanese Circulation Society. All rights reserved. Background: The natural course of heart failure (HF) is typically associated with repeated hospitalizations, and subsequently, patient prognosis deteriorates. However, the precise relationship between repeated admissions for HF and long-term prognosis remains unknown. Methods and Results: We analyzed data from 1,730 consecutive acute HF patients registered in the West Tokyo Heart Failure (WET-HF) registry between June 2005 and April 2014 (median age, 76 years). Patients were divided into 3 groups according to the number of previous HF admissions at the time of the index admission (0, n=876 [55.4%]; 1, n=425 [26.9%]; ≥2, n=279 [17.7%] previous admissions). A history of multiple previous admissions was an independent predictor for all-cause death and HF readmission in reference to a history of a single previous admission (hazard ratio (HR), 1.53; 95% confidence interval (CI) 1.10–2.13; HR, 1.90 95% CI, 1.47–2.44, respectively) or no previous admissions (HR, 1.37, 95% CI, 1.01–1.85; HR, 2.83, 95% CI, 2.19–3.65, respec-tively). On the other hand, a history of a single previous admission was an independent predictor for HF readmission in reference to a history of no previous admissions (HR, 1.51, 95% CI, 1.18–1.92), but not for all-cause death (HR, 0.89, 95% CI, 0.66–1.20). Conclusions: Based on a contemporary multicenter HF registry, a history of multiple previous HF admissions was revealed as an independent, strong risk factor of adverse events following the index admission. The number of hospitalizations could be a simple and important surrogate indicating subsequent adverse events in patients with HF.

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Outcome of hospitalised heart failure in Japan and the United Kingdom stratified by plasma N-terminal pro-B-type natriuretic peptide

Shiraishi Y, Nagai T, Kohsaka S, Goda A, Nagatomo Y, Mizuno A, Kohno T, Rigby A, Fukuda K, Yoshikawa T, Clark A, Cleland J

Clinical Research in Cardiology 107 ( 12 ) 1103 - 1110 2018.12

Research paper (scientific journal), Lead author, Accepted, ISSN 18610684

© 2018, Springer-Verlag GmbH Germany, part of Springer Nature. Background: Mortality subsequent to a hospitalisation for heart failure is reported to be much lower in Japan than in the United Kingdom (UK). This could reflect differences in disease severity or in management. Accordingly, we directly compared patient backgrounds and outcomes between Japan and UK. Methods: Consecutive patients admitted to academic hospitals in the UK and Japan with heart failure had a common set of variables, including plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), collected during admission. Mortality during hospitalisations, at 90 and 180 days was recorded and stratified by quintile of NT-proBNP. Results: Overall, 935 patients were enrolled; 197 from UK and 738 from Japan. Median (interquartile range) age [UK: 78 (71–88) vs. Japan: 78 (70–84) years; p = 0.947], glomerular filtration rate [UK: 49 (34–68) vs. Japan: 49 (33–65) ml/min/1.73 m 2 ; p = 0.209] and plasma NT-proBNP [UK: 4957 (2278–10,977) vs. Japan: 4155 (1972–9623) ng/l; p = 0.186] were similar, but systolic blood pressure was lower in the UK [118 (105–131) vs. 137 (118–159) mmHg; p < 0.001]. Patients with a higher plasma NT-proBNP had a worse prognosis in both countries; in-hospital and post-discharge mortality rates were higher in the UK even after adjusting for prognostic variables including NT-proBNP. Conclusions: This analysis suggests that either unobserved differences in patient characteristics or differences in care (formal or informal) rather than greater heart failure severity may account for the worse outcome of heart failure in the UK compared to Japan.

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【心不全(第2版)上-最新の基礎・臨床研究の進歩-】疫学　コホート研究　日本におけるコホート研究　WET-HF研究

白石泰之, 香坂俊

日本臨床 ((株)日本臨床社) 76 ( 増刊9 心不全(上) ) 76 - 82 2018.12

ISSN 0047-1852

【循環器集中治療Break Through】急性心不全治療の新展開　時間軸に基づくアプローチは本当に重要なのか?

白石泰之

ICUとCCU (医学図書出版(株)) 42 ( 11 ) 705 - 712 2018.11

ISSN 0389-1194

「心不全パンデミック」は医療だけでなく、社会・経済的に大きな問題となる可能性をはらんでいる。世界で有数の「超高齢化社会」である日本もその例外ではなく、今後心不全患者数が増加の一途をたどることは確実である。心不全診療のなかでも、最もコストと労力を要する分野が急性期治療であり、現在の本邦の急性心不全患者の長期予後(1年死亡率は20%前後)は海外と比較して良好であるが、現状のまま高齢化が続けば早々に予後は悪化に転ずることが予想される。心不全患者の全般的な予後を改善させるためには、抜本的な戦略が必要であり、その1つが「時間軸」に基づいた治療戦略(早期介入)の導入であると考えられている。ただし、すべての急性心不全患者が早期介入の恩恵を受けるといえば嘘であり、昨今のランダム化比較試験でも証明されている。膨れあがる心不全医療費とのバランスを図りつつ、効率的かつ効果的な医療を達成するためには、個別の病態とリスクに応じて、早期介入の恩恵を受けやすい患者に優先的にアプローチしていく姿勢が必要である。(著者抄録)

9-year Trend in the Management of Acute Heart Failure in Japan: A Report from the National Consortium of Acute Heart Failure Registries

Shiraishi Y., Kohsaka S., Sato N., Takano T., Kitai T., Yoshikawa T., Matsue Y.

Journal of the American Heart Association (Journal of the American Heart Association) 7 ( 18 ) e008687 2018.09

Research paper (scientific journal), Lead author, Accepted

© 2018 The Authors. Background-—Acute heart failure (AHF) is a heterogeneous condition, and its characteristics and management patterns differ by region. Furthermore, limited evidence is available on AHF outside of Western countries. A project by the National Consortium of Acute Heart Failure Registries was designed to evaluate the trends over time in patient backgrounds, in-hospital management patterns, and long-term outcomes of patients with AHF over 9 years in Japan. Methods and Results-—Between 2007 and 2015, registry data for patients with AHF were collected from 3 large-scale quality AHF registries (ATTEND/WET-HF/REALITY-AHF). Predefined end points were trends over time in age, sex, and clinical outcomes, including short- and long-term mortality and readmission for heart failure. The final data set consisted of 9075 patients with AHF. No significant differences in patient backgrounds and laboratory findings (eg, anemia or renal function) were observed, with the exception of patient age; mean age became substantially higher over 9 years (71.6–77.0 years; P for trend, <0.001). On the contrary, length of hospital stay became shorter (mean, 26–16 days). These changes were not associated with in-hospital mortality (4.7–7.5%) or 30-day heart failure readmission rate (4.8–5.4%), as well as 1-year mortality and heart failure readmission rate (20.1– 23.3% and 23.6–26.2%, respectively). Conclusions-—Length of hospital stay in patients with AHF shortened over the 9-year period despite the increasing age of the patients. However, short- and long-term outcomes do not seem to be affected; continuous efforts to monitor clinical outcomes in patients with AHF are needed.

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Impact of catheter-induced iatrogenic coronary artery dissection with or without postprocedural flow impairment: A report from a Japanese multicenter percutaneous coronary intervention registry

Hiraide T., Sawano M., Shiraishi Y., Ueda I., Numasawa Y., Noma S., Negishi K., Ohki T., Yuasa S., Hayashida K., Miyata H., Fukuda K., Kohsaka S.

PLoS ONE (PLoS ONE) 13 ( 9 ) e0204333 2018.09

© 2018 Hiraide et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Despite the ever-increasing complexity of percutaneous coronary intervention (PCI), the incidence, predictors, and in-hospital outcomes of catheter-induced coronary artery dissection (CICAD) is not well defined. In addition, there are little data on whether persistent coronary flow impairment after CICAD will affect clinical outcomes. We evaluated 17,225 patients from 15 participating hospitals within the Japanese PCI registry from January 2008 to March 2016. Associations between CICAD and in-hospital adverse cardiovascular events were evaluated using multivariate logistic regression. Outcomes of patients with CICAD with or without postprocedural flow impairment (TIMI flow 2 or 3, respectively) were analyzed. The population was predominantly male (79.4%; mean age, 68.2 ± 11.0 years); 35.6% underwent PCI for complex lesions (eg. chronic total occlusion or a bifurcation lesion.). CICAD occurred in 185 (1.1%), and its incidence gradually decreased (p < 0.001 for trend); postprocedural flow impairment was observed in 43 (23.2%). Female sex, complex PCI, and target lesion in proximal vessel were independent predictors (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.53–3.10; OR, 2.19; 95% CI, 1.58–3.04; and OR, 1.55; 95% CI, 1.06–2.28, respectively). CICAD was associated with an increased risk of in-hospital adverse events (composite of new-onset cardiogenic shock and new-onset heart failure) regardless of postprocedural flow impairment (OR, 10.9; 95% CI, 5.30–22.6 and OR, 2.27; 95% CI, 1.20–4.27, respectively for flow-impaired and flow-recovered CICAD). In conclusion, CICAD occurred in roughly 1% of PCI cases; female sex, complex PCI, and proximal lesion were its independent risk factors. CICAD was associated with adverse in-hospital cardiovascular events regardless of final flow status. Our data implied that the appropriate selection of PCI was necessary for women with complex lesions.

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Mortality after admission for heart failure in the UK compared with Japan

Nagai T., Sundaram V., Rothnie K., Quint J., Shoaib A., Shiraishi Y., Kohsaka S., Piper S., McDonagh T., Hardman S., Goda A., Mizuno A., Kohno T., Rigby A., Yoshikawa T., Clark A., Anzai T., Cleland J.

Open Heart (Open Heart) 5 ( 2 ) e000811 2018.08

ISSN 2053-3624

© Author(s) (or their employer(s)) 2018. Objective Mortality amongst patients hospitalised for heart failure (HHF) in Western and Asian countries may differ, but this has not been investigated using individual patient-level data (IPLD). We sought to remedy this through rigorous statistical analysis of HHF registries and variable selection from a systematic literature review. Methods and results IPLD from registries of HHF in Japan (n=3781) and the UK (n=894) were obtained. A systematic literature review identified 23 models for predicting outcome of HHF. Five variables appearing in 10 or more reports were strongly related to prognosis (systolic blood pressure, serum sodium concentration, age, blood urea nitrogen and creatinine). To compare mortality in the UK and Japan, variables were imputed in a propensity model using inverse probability of treatment weighting (IPTW) and IPTW with logistic regression (doubly robust IPTW). Overall, patients in the UK were sicker and in-patient and post-discharge mortalities were greater, suggesting that the threshold for hospital admission was higher. Covariate-adjusted in-hospital mortality was similar in the UK and Japan (IPTW OR: 1.14, 95% CI 0.70 to 1.86), but 180-day postdischarge mortality was substantially higher in the UK (doubly robust IPTW OR: 2.33, 95% CI 1.58 to 3.43). Conclusions Despite robust methods to adjust for differences in patient characteristics and disease severity, HHF patients in the UK have roughly twice the mortality at 180 days compared with those in Japan. Similar analyses should be done using other data sets and in other countries to determine the consistency of these findings and identify factors that might inform healthcare policy and improve outcomes.

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Performance of the MAGGIC heart failure risk score and its modification with the addition of discharge natriuretic peptides

Sawano M., Shiraishi Y., Kohsaka S., Nagai T., Goda A., Mizuno A., Sujino Y., Nagatomo Y., Kohno T., Anzai T., Fukuda K., Yoshikawa T.

ESC Heart Failure (ESC Heart Failure) 5 ( 4 ) 610 - 619 2018.08

Research paper (scientific journal), Accepted

© 2018 The Authors. Aims Predictive models for heart failure patients are widely used in the clinical practice to stratify patients’ mortality and enable clinicians to tailor and intensify their approach. However, such models have not been validated internationally. In addition, biomarkers are now frequently measured to obtain prognostic information, and the implications of this practice are not known. In this study, we aimed to validate the model performance of the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) score in a Japanese acute heart failure registry and further explore the incremental prognostic value of discharge B-type natriuretic peptide (BNP) level. Methods and Results In this study, we evaluated the registered data of 2215 consecutive acute HF patients (with 694 119 person-years follow-up) from a prospective multicentre registry (the West Tokyo Heart Failure) conducted in Japan from April 2006 to August 2016. The mean age was 73.0 ± 13.0, and 61.2% were male. The MAGGIC score demonstrated modest discrimination (c-index = 0.71, 95% confidence interval 0.67–0.74) and good calibration (R2 value = 0.97); there was constant overestimation for 1 year mortality. However, when the BNP level was added to the original MAGGIC variables, the model demonstrated good discrimination (c-index = 0.74, 95% confidence interval 0.70–0.78) with adequate calibration (R2 value = 0.91). The modified MAGGIC BNP score was externally validated in a separate Japanese registry (NaDEF) and demonstrated moderate discrimination (c-index = 0.69, 95% confidence interval 0.65–0.73) and calibration (R2 value = 0.85). Conclusion The original MAGGIC score performed modestly in Japanese patients, but the addition of discharge BNP level enhanced model performance. The addition of objective biomarkers may result in effective modification of preexisting internationally recognized risk models and aid in multinational comparisons of heart failure patients’ outcomes.

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Validation of U.S. mortality prediction models for hospitalized heart failure in the United Kingdom and Japan

Nagai T., Sundaram V., Shoaib A., Shiraishi Y., Kohsaka S., Rothnie K., Piper S., McDonagh T., Hardman S., Goda A., Mizuno A., Sawano M., Rigby A., Quint J., Yoshikawa T., Clark A., Anzai T., Cleland J.

European Journal of Heart Failure (European Journal of Heart Failure) 20 ( 8 ) 1179 - 1190 2018.08

ISSN 13889842

© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology Aims: Prognostic models for hospitalized heart failure (HHF) were developed predominantly for patients of European origin in the United States of America; it is unclear whether they perform similarly in other health care systems or for different ethnicities. We sought to validate published prediction models for HHF in the United Kingdom (UK) and Japan. Methods and results: Patients in the UK (n =894) and Japan (n =3158) were prospectively enrolled and were similar in terms of sex (∼60% men) and median age (∼77 years). Models predicted that British patients would have a higher mortality than Japanese, which was indeed true both for in-hospital (4.8% vs. 2.5%) and 180-day (20.7% vs. 9.5%) mortality. The model c-statistics for the published/derivation (range 0.70–0.76) and Japanese (range 0.75–0.77) cohorts were similar and higher than for the UK (0.62–0.75) but models consistently overestimated mortality in Japan. For in-hospital mortality, the OPTIMIZE-HF model performed best, providing similar discrimination in published/derivation, UK and Japanese cohorts [c-indices: 0.75 (0.74–0.77); 0.75 (0.68–0.81); and 0.77 (0.70–0.83), respectively], and least overestimated mortality in Japan. For 180-day mortality, the c-statistics for the ASCEND-HF model were similar in published/derivation (0.70) and UK [0.69 (0.64–0.74)] cohorts but higher in Japan [0.75 (0.71–0.79)]; calibration was good in the UK but again overestimated mortality in Japan. Conclusion: Calibration of published prediction models appears moderately accurate and unbiased when applied to British patients but consistently overestimates mortality in Japan. Identifying the reason why patients in Japan have a better than predicted prognosis is of great interest.

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Incidence of hospital-acquired hyponatremia by the dose and type of diuretics among patients with acute heart failure and its association with long-term outcomes

Yamazoe M., Mizuno A., Kohsaka S., Shiraishi Y., Kohno T., Goda A., Higuchi S., Yagawa M., Nagatomo Y., Yoshikawa T.

Journal of Cardiology (Journal of Cardiology) 71 ( 6 ) 550 - 556 2018.06

ISSN 09145087

© 2018 Background: Diuretics are the cornerstone therapy for acute heart failure (AHF) but can lead to various electrolyte disturbances and inversely affect the patients’ outcome. We aimed to evaluate whether (1) the dose of loop diuretics could predict hospital-acquired hyponatremia (HAH) during AHF treatment, (2) addition of thiazide diuretics could affect development of HAH, and (3) assess their impact on long-term outcomes. Methods: We analyzed the subjects enrolled in the multicenter AHF registry (WET-HF). Risk of HAH, defined as hyponatremia at discharge with normonatremia upon admission, was evaluated based on oral non-potassium-sparing diuretics via multivariate logistic regression analysis. Additionally, we performed one-to-one matched analysis based on propensity scores for thiazide diuretics use and compared long-term mortality. Results: Of total 1163 patients (mean age 72.6 ± 13.6 years, male 62.6%), 92 (7.9%) had HAH. Compared with low-dose loop diuretics users (<40 mg; without thiazide diuretics), risks for developing HAH were significantly higher in patients with thiazide diuretics, regardless of the dose of loop diuretics (OR 2.67, 95% CI 1.13–6.34 and OR 2.31, 95% CI 1.50–5.13 for low- and high-dose loop diuretics, respectively). The association was less apparent in patients without thiazide diuretics (OR 1.29, 95% CI 0.73–2.27 for high-dose loop diuretics alone). Among 206 matched patients, all-cause and cardiac mortality rate was 27% and 14% in non thiazide diuretics users and 50% and 30% in thiazide diuretics users, respectively (HR 2.46, 95% CI 1.29–4.69, p = 0.006 and HR 2.50, 95% CI 1.10–5.67, p = 0.028, respectively) during a mean 19.3 months of follow-up. Conclusions: Thiazide diuretics use, rather than loop diuretics dose, was independently associated with HAH; and mortality was higher in thiazide diuretics users even after statistical matching.

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【循環器診療のギモン、百戦錬磨のエキスパートが答えます!救急、病棟でのエビデンスに基づいた診断・治療・管理】(第1章)ER・急性期病棟におけるギモン　診断編　2018年現在、心不全の診断は実際どれがスタンダードなのか?

白石泰之

レジデントノート ((株)羊土社) 20 ( 5 ) 677 - 682 2018.06

ISSN 1344-6746

【徹底理解・心機能　何をいつ測り、どう活かす?】診る　病歴と身体所見で診る心機能　時間軸を視野にいれた心機能評価

庄司聡, 白石泰之, 香坂俊

Heart View ((株)メジカルビュー社) 22 ( 4 ) 298 - 302 2018.04

ISSN 1342-6591

＜Point＞1 心不全の管理にはBNPやエコーなどの「検査」に目が向きがちだが、病歴・身体所見は非侵襲的かつ迅速に情報を得ることができ、早期診断・治療方針決定双方の鍵となりうる。2 このなかでも血圧は治療方針決定の鍵であり、このほか起座呼吸・夜間発作性呼吸困難、さらにIII音・頸静脈怒張は診断の特異度が高い。3 急性心不全では早期診断・治療の遅れが予後と関連することが明らかとなっており、病歴・身体所見を活かし、時間軸を意識して早期の介入を行っていく必要がある。(著者抄録)

Long-Term Prognostic Significance of Plasma B-Type Natriuretic Peptide Level in Patients With Acute Heart Failure With Reduced, Mid-Range, and Preserved Ejection Fractions

Hamatani Y., Nagai T., Shiraishi Y., Kohsaka S., Nakai M., Nishimura K., Kohno T., Nagatomo Y., Asaumi Y., Goda A., Mizuno A., Yasuda S., Ogawa H., Yoshikawa T., Anzai T.

American Journal of Cardiology (American Journal of Cardiology) 121 ( 6 ) 731 - 738 2018.03

ISSN 00029149

© 2017 Elsevier Inc. Plasma B-type natriuretic peptide (BNP) is an important prognostic marker in patients with acute heart failure (AHF). However, it is unclear which BNP parameter, on admission, at discharge, or change during hospitalization, has the highest predictive performance for long-term adverse outcomes, and whether its prognostic impact differs according to the new European heart failure (HF) phenotype classification by left ventricular ejection fraction: heart failure with reduced ejection fraction (HFrEF), heart failure with mid-range ejection fraction (HFmrEF), and heart failure with preserved ejection fraction (HFpEF). We examined 1,792 patients with AHF consisting of 860 (48%) HFrEFs, 318 (18%) HFmrEFs, and 614 (34%) HFpEFs. Prognostic performance of each BNP parameter was assessed by the Harrell c-index. During a median follow-up of 664 days, 344 (19%) patients died. Discharge BNP had the highest c-index (0.69) for mortality among all BNP parameters (p <0.001). In multivariate Cox proportional hazard modeling, discharge BNP was associated with mortality in HFrEF, HFmrEF, and HFpEF patients with significant interaction (hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.57 to 2.41; HR 1.76, 95% CI 1.10 to 2.82; HR 1.46, 95% CI 1.12 to 1.91, respectively; p = 0.011 for interaction). Moreover, the c-index of discharge BNP for mortality in HFrEF patients (0.72) was higher than that in HFmrEF patients (0.68) and HFpEF patients (0.65). Similar results were obtained for mortality or HF rehospitalization as alternative outcomes, except there was no statistically significant interaction among HF phenotypes. In conclusion, discharge BNP is a more reliable marker than other BNP parameters on long-term outcome prediction in patients with AHF, but its prognostic impact may be weakened in HFmrEF and HFpEF compared with HFrEF.

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Impact of Triggering Events on Outcomes of Acute Heart Failure

Shiraishi Y, Kohsaka S, Abe T, Harada K, Miyazaki T, Miyamoto T, Iida K, Tanimoto S, Yagawa M, Takei M, Nagatomo Y, Hosoda T, Yamamoto T, Nagao K, Takayama M

American Journal of Medicine 131 ( 2 ) 156 - 164.e2 2018.02

Research paper (scientific journal), Lead author, Accepted, ISSN 00029343

Background: The onset of acute heart failure is known to be associated with increased physical activity and other specific behaviors that can trigger hemodynamic deterioration. This analysis aimed to describe the distribution of triggers in patients hospitalized for acute heart failure, and investigate their effects on in-hospital outcomes. Methods: Consecutive patients hospitalized for acute heart failure between 2010 and 2014 were registered in a multicenter data registration system (72 institutions within Tokyo, Japan). Baseline demographics and in-hospital mortality were extracted from 17,473 patients. Patients with a trigger were grouped based on their triggering event: those with onset during (a) physical activity; (b) sleeping; (c) eating or watching television; (d) bathing or excretion (use of restrooms); and (e) engaging in other activities. These patients were compared with patients without identifiable triggers. Multiple imputation was used for missing data. Results: Patients were predominantly men (57.1%), with a mean age of 76.0 ± 13.0 years; a triggering event was present in 49.1%. No significant difference in baseline characteristics was noted between groups except for younger age, higher blood pressure, and prevalence of signs of congestion in the trigger-positive group. In-hospital mortality rate was 7.9%. Presence of triggers was positively associated with a reduced risk of in-hospital mortality (adjusted odds ratio 0.79; 95% confidence interval, 0.70-0.90; P =.0003). In a delta-adjusted pattern mixture model, the effect of a triggering event on in-hospital mortality remained consistently significant. Conclusion: Triggering events for acute heart failure can provide additional information for risk prediction. Efforts to identify the triggers should be made to classify patients according to risk group.

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Real-time analysis of the heart rate variability during incremental exercise for the detection of the ventilatory threshold

Shiraishi Y, Katsumata Y, Sadahiro T, Azuma K, Akita K, Isobe S, Yashima F, Miyamoto K, Nishiyama T, Tamura Y, Kimura T, Nishiyama N, Aizawa Y, Fukuda K, Takatsuki S

Journal of the American Heart Association 7 ( 1 ) 2018.01

Research paper (scientific journal), Lead author, Accepted

Background: It has never been possible to immediately evaluate heart rate variability (HRV) during exercise. We aimed to visualize the real-time changes in the power spectrum of HRV during exercise and to investigate its relationship to the ventilatory threshold (VT). Methods and Results: Thirty healthy subjects (29.1±5.7 years of age) and 35 consecutive patients (59.0±13.2 years of age) with myocardial infarctions underwent cardiopulmonary exercise tests with an RAMP protocol ergometer. The HRV was continuously assessed with power spectral analyses using the maximum entropy method and projected on a screen without delay. During exercise, a significant decrease in the high frequency (HF) was followed by a drastic shift in the power spectrum of the HRV with a periodic augmentation in the low frequency/HF (L/H) and steady low HF. When the HRV threshold (HRVT) was defined as conversion from a predominant high frequency (HF) to a predominant low frequency/HF (L/H), the VO2 at the HRVT (HRVT-VO2) was substantially correlated with the VO2 at the lactate threshold and VT) in the healthy subjects (r=0.853 and 0.921, respectively). The mean difference between each threshold (0.65 mL/kg per minute for lactate threshold and HRVT, 0.53 mL/kg per minute for VT and HRVT) was nonsignificant (P > 0.05). Furthermore, the HRVT-VO2 was also correlated with the VT-VO2 in these myocardial infarction patients (r=0.867), and the mean difference was -0.72 mL/kg per minute and was nonsignificant (P > 0.05). Conclusions: A HRV analysis with our method enabled real-time visualization of the changes in the power spectrum during exercise. This can provide additional information for detecting the VT.

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Stroke after percutaneous coronary intervention in the era of transradial intervention report from a Japanese multicenter registry

Shoji S., Kohsaka S., Kumamaru H., Sawano M., Shiraishi Y., Ueda I., Noma S., Suzuki M., Numasawa Y., Hayashida K., Yuasa S., Miyata H., Fukuda K.

Circulation: Cardiovascular Interventions (Circulation: Cardiovascular Interventions) 11 ( 12 ) e006761 2018

ISSN 19417640

© 2018 American Heart Association, Inc. BACKGROUND: Periprocedural stroke is a rare but life-threatening complication of percutaneous coronary intervention (PCI). Transradial intervention (TRI) is more beneficial than transfemoral intervention for periprocedural bleeding and acute kidney injuries, but its effect on periprocedural stroke has not been fully investigated. Our study aimed to assess risk predictors of periprocedural stroke according to PCI access site. METHODS AND RESULTS: Between 2008 and 2016, 17966 patients undergoing PCI were registered in a prospective multicenter database. Periprocedural stroke was defined as loss of neurological function caused by an ischemic or hemorrhagic event with residual symptoms lasting at least 24 hours after onset. Periprocedural stroke was observed in 42 patients (0.3%). Stroke patients were older and had a higher incidence of chronic kidney disease, peripheral artery disease, and acute coronary syndrome but were less likely to undergo TRI. Multivariable logistic regression analysis revealed TRI (odds ratio; 0.33; 95% CI, 0.16-0.71; P=0.004) was significantly associated with a lower occurrence of periprocedural stroke. Finally, propensity score-matching analysis showed that TRI was associated with a reduced risk of periprocedural stroke compared with transfemoral intervention (0.1% versus 0.4%; P=0.014). According to our sensitivity analysis, this finding was robust to the presence of an unmeasured confounder in almost all plausible scenarios. CONCLUSIONS: TRI was associated with a reduced risk of periprocedural stroke compared with transfemoral intervention. Increased TRI use may reduce overall PCI complications and should be recommended as the optimal access site for both urgent/emergent and elective PCIs.

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Identification of left atrial appendage thrombi in patients with persistent and long-standing persistent atrial fibrillation using intra-cardiac echocardiography and cardiac computed tomography

Ikegami Y., Tanimoto K., Inagawa K., Shiraishi Y., Fuse J., Sakamoto M., Momiyama Y., Takatsuki S.

Circulation Journal (Circulation Journal) 82 ( 1 ) 46 - 52 2018

ISSN 13469843

© 2017, Japanese Circulation Society. All rights reserved. Background: Intracardiac echocardiography (ICE) and cardiac computed tomography (CCT), in addition to standard transesophageal echocardiography (TEE), have been used to identify left atrial (LA) thrombi prior to ablation for atrial fibrillation (AF). The clinical advantages of this, however, remain unclear. This study therefore investigated the advantages of additional pre-procedural LA appendage (LAA) thrombus evaluation using ICE and the clinical value of CCT in persistent and long-standing persistent AF. Methods and Results: We analyzed data from 108 consecutive patients with persistent and long-standing persistent AF who were scheduled to undergo AF ablation. TEE was performed within 24 h prior to ablation. ICE was performed for 97 patients in whom a thrombus was not detected on TEE. CCT was performed in 95 patients. Thrombus or sludge was detected on TEE in 11 patients (10.3%), for whom ablation was cancelled. Four additional patients were diagnosed with LAA thrombus on ICE. When TEE and ICE were used as the reference for thrombus detection, the sensitivity, specificity, positive predictive value, and negative predictive value of CCT for identifying contrast defects in the LAA were 100%, 81.0%, 40.7%, and 100%, respectively. Conclusions: ICE combined with TEE increased the detection rate of LAA thrombi in patients with persistent and long-standing persistent AF. Moreover, CCT had high sensitivity and negative predictive value for LAA thrombus detection.

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