Updated on 2024/03/26

写真a

 
HIRAIWA HIROAKI
 
Organization
Nagoya University Hospital Cardiology Assistant professor of hospital
Title
Assistant professor of hospital
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Degree 1

  1. 博士(医学) ( 2019.3   名古屋大学 ) 

Research Interests 4

  1. 心臓リハビリテーション

  2. 植込型左室補助人工心臓

  3. 体外式補助循環

  4. 重症心不全

Research Areas 1

  1. Life Science / Cardiology  / 臨床心不全

Research History 2

  1. Nagoya University   Department of Cardiology   Assistant professor of hospital

    2021.4

  2. Nagoya University   Department of Emergency and Critical Care Medicine   Assistant professor of hospital

    2019.4 - 2021.3

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    Country:Japan

Education 2

  1. Nagoya University   Graduate School of Medicine

    - 2019.3

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    Country: Japan

  2. Nagoya University   Graduate School of Medicine   Graduate School of Medicine

    - 2009.3

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    Country: Japan

Professional Memberships 10

  1. 日本移植学会

  2. 日本人工臓器学会

  3. 日本集中治療学会

  4. 日本心血管インターベンション治療学会

  5. 日本心臓リハビリテーション学会

  6. 日本腫瘍循環器学会

  7. 日本心不全学会

  8. 日本心臓病学会

  9. 日本循環器学会

  10. 日本内科学会

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Papers 87

  1. Prospective Analysis of Immunosuppressive Therapy in Cardiac Sarcoidosis With Fluorodeoxyglucose Myocardial Accumulation: The PRESTIGE Study.

    Morimoto R, Unno K, Fujita N, Sakuragi Y, Nishimoto T, Yamashita M, Kuwayama T, Hiraiwa H, Kondo T, Kuwatsuka Y, Okumura T, Ohshima S, Takahashi H, Ando M, Ishii H, Kato K, Murohara T

    JACC. Cardiovascular imaging   Vol. 17 ( 1 ) page: 45 - 58   2024.1

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    Background: Fluorodeoxyglucose positron emission tomography (18F-FDG-PET) can noninvasively assess active inflammatory myocardium in patients with cardiac sarcoidosis (CS). Prednisolone (PSL) is the initial drug of choice for active CS; however, its efficacy has not been prospectively evaluated. Moreover, there are no alternative systematic treatment strategies. Objectives: The goal of this study was to evaluate the efficacy of methotrexate (MTX) in patients refractory to PSL assessed by using cardiac metabolic activity (CMA) in 18F-FDG-PET. Methods: A total of 59 patients with active CS were prospectively enrolled. CMA (standardized uptake value × accumulation area) was used as an indicator of active inflammation, and a 6-month regimen of PSL therapy was introduced, followed by a second FDG scan. Poor responders to PSL therapy (CMA reduction rate <70%) and patients with recurrent CS (CMA reduction rate ≥70% after initial PSL therapy but CMA recurred after an additional 6 months of therapy) were randomly assigned to the MTX or repeat PSL (re-PSL) therapy groups for another 6 months. Results: Fifty-six patients completed the initial 6-month PSL therapy regimen. Median CMA reduced from 203.3 to 1.0 (P < 0.001), and 47 patients were allocated to the response group, 9 to the poor response group, and 2 to the recurrent group. Accordingly, 11 patients were randomly assigned to the MTX (n = 5) or re-PSL (n = 6) groups. After 6 months, neither group showed a significant reduction in CMA values. MTX was comparable to re-PSL in reducing CMA. Conclusions: The 6-month regimen of PSL was a potent therapeutic tool for active CS. When MTX was added to low-dose PSL in patients refractory to the initial PSL therapy, there was no significant difference compared with re-PSL. Further studies are needed to evaluate the therapeutic potential of MTX for active CS, including how MTX works when it is administered in higher doses or for longer periods.

    DOI: 10.1016/j.jcmg.2023.05.017

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  2. The Balance of CD8-Positive T Cells and PD-L1 Expression in the Myocardium Predicts Prognosis in Lymphocytic Fulminant Myocarditis.

    Hiraiwa H, Morimoto R, Tsuyuki Y, Ushida K, Ito R, Kazama S, Kimura Y, Araki T, Mizutani T, Oishi H, Kuwayama T, Kondo T, Okumura T, Murohara T

    Cardiology   Vol. 149 ( 1 ) page: 28 - 39   2024

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    Introduction: The clinical significance and prognostic value of T cell involvement and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) have not been established in lymphocytic fulminant myocarditis (FM). We investigated the prognostic impact of the number of CD4+, CD8+, FoxP3+, and PD-1+ T cells, as well as PD-L1 expression, in cardiomyocytes in lymphocytic FM. Methods: This is a single-center observational cohort study. Myocardial tissue was obtained from 16 consecutive patients at lymphocytic FM onset. The median follow-up was 140 days. Cardiac events were defined as a composite of cardiac death and left ventricular-assist device implantation. CD4, CD8, FoxP3, PD-1, and PD-L1 immunostaining were performed on myocardial specimens. Results: The median age of the patients was 52 years (seven men and nine women). There was no significant difference in the number of CD4+ cells. The number of CD8+ cells and the CD8+/CD4+ T cell ratio were higher in the cardiac event group (Event+) than in the group without cardiac events (Event−) (p = 0.048 and p = 0.022, respectively). The number of FoxP3+ T cells was higher in the Event+ group (p = 0.049). Although there was no difference in the number of PD-1+ cells, cardiomyocyte PDL1 expression was higher in the Event+ group (p = 0.112). Event-free survival was worse in the group with a high CD8+ cell count (p = 0.012) and high PD-L1 expression (p = 0.049). When divided into three groups based on the number of CD8+ cells and PD-L1 expression (CD8highPDL1high [n = 8], CD8lowPD-L1high [n = 1], and CD8lowPD-L1low [n = 7]), the CD8highPD-L1high group demonstrated the worst event-free survival, while the CD8lowPD-L1high group had a favorable prognosis without cardiac events (p = 0.041). Conclusion: High myocardial expression of CD8+ T cells and PD-L1 may predict a poor prognosis in lymphocytic FM.

    DOI: 10.1159/000534518

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  3. 特集 もう迷わない! 循環器薬物処方〜若手医師へ贈る熟練医の処方の考え方 III 実臨床で迷うことがある病態での薬物治療の実際 1. 高血圧を合併したHFpEFに対する急性期と慢性期の薬物治療

    平岩 宏章, 奥村 貴裕, 室原 豊明

    Heart View   Vol. 27 ( 12 ) page: 120 - 125   2023.11

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    Publisher:メディカルレビュー社  

    DOI: 10.18885/hv.0000001402

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  4. Implications of uremic cardiomyopathy for the practicing clinician: an educational review.

    Hiraiwa H, Kasugai D, Okumura T, Murohara T

    Heart failure reviews   Vol. 28 ( 5 ) page: 1129 - 1139   2023.9

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    Studies over recent years have redeveloped our understanding of uremic cardiomyopathy, defined as left ventricular hypertrophy, congestive heart failure, and associated cardiac hypertrophy plus other abnormalities that result from chronic kidney disease and are often the cause of death in affected patients. Definitions of uremic cardiomyopathy have conflicted and overlapped over the decades, complicating the body of published evidence, and making comparison difficult. New and continuing research into potential risk factors, including uremic toxins, anemia, hypervolemia, oxidative stress, inflammation, and insulin resistance, indicates the increasing interest in illuminating the pathways that lead to UC and thereby identifying potential targets for intervention. Indeed, our developing understanding of the mechanisms of UC has opened new frontiers in research, promising novel approaches to diagnosis, prognosis, treatment, and management. This educational review highlights advances in the field of uremic cardiomyopathy and how they may become applicable in practice by clinicians. Pathways to optimal treatment with current modalities (with hemodialysis and angiotensin-converting enzyme inhibitors) will be described, along with proposed steps to be taken in research to allow evidence-based integration of developing investigational therapies.

    DOI: 10.1007/s10741-023-10318-1

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  5. Cardiac sympathetic activity and relationship to cardiac events and left ventricular reverse remodeling in patients with non-ischemic dilated cardiomyopathy.

    Mizutani T, Morimoto R, Isobe S, Ito R, Araki T, Kimura Y, Kazama S, Oishi H, Kuwayama T, Hiraiwa H, Kondo T, Okumura T, Murohara T

    Annals of nuclear medicine   Vol. 37 ( 8 ) page: 451 - 461   2023.8

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    Background: Delayed heart-to-mediastinum ratio (HMR) has been associated with catecholamine levels and contractile reserve in dilated cardiomyopathy (DCM); however, there is scant evidence regarding the association between cardiac sympathetic activity and left ventricular reverse remodeling (LV-RR). We calculated the 123I-metaiodobenzylguanidine (123I-mIBG) HMR and washout rate (WR) in patients with DCM and investigated their associations with LV-RR. Methods: From April 2003 to January 2020, in 120 patients with DCM who underwent 123I-mIBG scintigraphy. 66 patients undergoing follow-up echo and taking a beta-blocker from baseline were examined the relationship between 123I-mIBG and LV-RR. After that, this prognostic value for composite cardiac events was evaluated in the entire 120 patients. Results: In LV-RR analysis, patients were 50.4 ± 12.2 years, with a mean left ventricular ejection fraction of 28.6%. Of 66 patients, 28 (42.4%) achieved LV-RR. Multiple logistic regression analysis of LV-RR revealed that not delayed HMR but the WR (cutoff value: 13.5%) was an independent predictor of LV-RR (odds ratio 6.514, p = 0.002). In the analysis for composite cardiac events, even though WR itself does not have the prognostic capacity, Kaplan–Meier survival curves divided by the cutoff value (delayed HMR = 2.0, WR = 13.5) showed that delayed HMR and WR values enabled the stratification of high-risk patients (log-rank p < 0.001). Conclusions: The 123I-mIBG WR was associated with the prevalence of LV-RR in patients taking 100% of beta-blockers and 98.5% of renin-angiotensin system inhibitors. Reflecting the contractile reserve, the combined assessment of the delayed HMR and WR could be used to further precisely stratify the patients with DCM.

    DOI: 10.1007/s12149-023-01838-9

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  6. Dynamic chest radiography as a novel minimally invasive hemodynamic imaging method in patients with heart failure.

    Hiraiwa H, Sakamoto G, Ito R, Koyama Y, Kazama S, Kimura Y, Kondo T, Morimoto R, Okumura T, Murohara T

    European journal of radiology   Vol. 161   page: 110729   2023.4

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    Purpose: Dynamic chest radiography allows for non-invasive cardiopulmonary blood flow assessment. However, data on its use for heart failure hemodynamic assessment are scarce. We utilized dynamic chest radiography to estimate heart failure hemodynamics. Method: Twenty heart failure patients (median age, 67 years; 17 men) underwent dynamic chest radiography and right heart catheterization. The analyzed images were 16-bit images (grayscale range: 0–65,535). Right atrial, right pulmonary artery, and left ventricular apex pixel values (average of the grayscale values of all pixels within a region of interest) were measured. The correlations of the minimum, maximum, mean, amount of change, and rate of change in pixel values with right atrial pressure, pulmonary artery pressure, pulmonary artery wedge pressure, and cardiac index were analyzed. Results: The mean right atrial pixel value and mean right atrial pressure (R = −0.576, P = 0.008), mean right pulmonary artery pixel value and mean pulmonary artery pressure (R = −0.546, P = 0.013), and left ventricular apex pixel value change rate and mean pulmonary artery wedge pressure (R = −0.664, P = 0.001) or cardiac index (R = 0.606, P = 0.005) were correlated. The left ventricular apex pixel value change rate identified low cardiac index (area under the curve, 0.792; 95% confidence interval, 0.590–0.993; P = 0.031) and low cardiac index with high pulmonary artery wedge pressure (area under the curve, 0.902; 95% confidence interval, 0.000–1.000; P = 0.030). Conclusions: Dynamic chest radiography is a minimally invasive tool for heart failure hemodynamic assessment.

    DOI: 10.1016/j.ejrad.2023.110729

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  7. 特集 二次性心筋症集中講座 診る5 【Expertise】ICUでよく診る病態:敗血症性心筋症と尿毒症性心筋症はどこまでわかっているのか?

    平岩 宏章, 奥村 貴裕, 室原 豊明

    Heart View   Vol. 27 ( 3 ) page: 226 - 232   2023.3

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    DOI: 10.18885/hv.0000001185

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  8. Increased risk of purge system malfunction after Impella 5.0 replacement: a case series.

    Oishi H, Morimoto R, Ito R, Kazama S, Kimura Y, Araki T, Mizutani T, Kuwayama T, Hiraiwa H, Kondo T, Okumura T, Mutsuga M, Usui A, Murohara T

    Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs   Vol. 26 ( 1 ) page: 79 - 83   2023.3

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    The Impella 5.0 is an axial-flow percutaneous ventricular assist device used in patients with cardiogenic shock. Although the recommended period of use is 10 days or less, weaning can be delayed because of ongoing hemodynamic instability. In clinical practice, this device sometimes malfunctions during long-term management with heparin and must be replaced; however, the relationship between the duration of support with the initial and replacement Impella 5.0 and the changes in value of the purge system has not been fully elucidated. From July 2018 to May 2021, Impella 5.0 was implanted and used for more than 10 days in 11 patients at our institution. Four patients required Impella replacement because of device malfunction and the second Impella had purge system malfunction in all cases. The second Impella was used for a significantly shorter time than the first Impella (p = 0016). We calculated the ratio of purge pressure to purge flow rate and found that the ratio exceeded 50 mm Hg/mL/h in all cases with purge system malfunction. In conclusion, it is important to construct a treatment strategy considering the duration of use, because the risk of purge system malfunction is high after replaced Impella 5.0.

    DOI: 10.1007/s10047-022-01337-0

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  9. Amino acid profiling to predict prognosis in patients with heart failure: an expert review.

    Hiraiwa H, Okumura T, Murohara T

    ESC heart failure   Vol. 10 ( 1 ) page: 32 - 43   2023.2

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    Heart failure is a complex disease with a poor prognosis. A number of widely used prognostic tools have limitations, so efforts to identify novel predictive markers and measures are important. As a metabolomics tool, amino acid profiling has shown promise in predicting heart failure prognosis; however, the evidence has not yet been sufficiently evaluated. We describe the utilization of amino acids in the healthy heart and in heart failure before reviewing the literature on amino acid profiling for prognostic prediction. We expertly interpret the findings and provide suggestions for future research to advance the understanding of the prognostic potential of amino acid profiling in heart failure. Our analysis revealed correlations between amino acid biomarkers and traditional prognostic factors, the additional prognostic value of amino acid biomarkers over traditional prognostic factors, and the successful use of amino acid biomarkers to distinguish heart failure aetiology. Although certain amino acid biomarkers have demonstrated additional prognostic value over traditional measures, such as New York Heart Association functional class, these measures are deeply rooted in clinical practice; thus, amino acid biomarkers may be best placed as additional prognostic tools to improve current risk stratification rather than as surrogate tools. Once the metabolic profiles of different heart failure aetiologies have been clearly delineated, the amino acid biomarkers with the most value in prognostic prediction should be determined. Amino acid profiling could be useful to evaluate the pathophysiology and metabolic status of different heart failure cohorts, distinguish heart failure aetiologies, and improve risk stratification and prognostic prediction.

    DOI: 10.1002/ehf2.14222

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  10. How Should Weight Control and Caloric Intervention Be Implemented for Obese Heart Failure Patients?

    Okumura T, Hiraiwa H, Takefuji M, Murohara T

    Cardiology   Vol. 148 ( 2 ) page: 103 - 105   2023

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    DOI: 10.1159/000527385

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  11. Early short course of neuromuscular blocking agents in patients with COVID-19 ARDS: a propensity score analysis

    Li Bassi G., Gibbons K., Suen J.Y., Dalton H.J., White N., Corley A., Shrapnel S., Hinton S., Forsyth S., Laffey J.G., Fan E., Fanning J.P., Panigada M., Bartlett R., Brodie D., Burrell A., Chiumello D., Elhazmi A., Esperatti M., Grasselli G., Hodgson C., Ichiba S., Luna C., Marwali E., Merson L., Murthy S., Nichol A., Ogino M., Pelosi P., Torres A., Ng P.Y., Fraser J.F., Al-Dabbous T., Alfoudri H., Shamsah M., Elapavaluru S., Berg A., Horn C., Mayasi Y., Schroll S., Meyer D., Velazco J., Ploskanych L., Fikes W., Bagewadi R., Dao M., White H., Meyer D., Ehlers A., Shalabi-McGuire M., Witt T., Grazioli L., Lorini L., Grandin E.W., Nunez J., Reyes T., OBriain D., Hunter S., Ramanan M., Affleck J., Veerendra H.H., Rai S., Russell-Brown J., Nourse M., Joseph M., Mitchell B., Tenzer M., Abe R., Cho H.J., Jeong I.S., Rahman N., Kakar V., Brozzi N., Mehkri O., Krishnan S., Duggal A., Houltham S., Graf J., Diaz R., Orrego R., Delgado C., González J., Sanchez M.S., Piagnerelli M., Sarrazin J.V., Zabert A./.G., Espinosa L., Delgado P., Delgado V., Rincón D.F.B., Yanten A.M.M., Duque M.B., Brodie D., Al-Hudaib A., Callahan M., Taufik M.A., Wardoyo E.Y., Gunawan M., Trisnaningrum N.S.

    Critical Care   Vol. 26 ( 1 )   2022.12

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    Background: The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis. Methods: We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2 days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48 h from commencement of IMV were compared with subjects who did not receive NMBAs or only upon commencement of IMV (control). The primary objective in the PS-matched cohort was comparison between groups in 90-day in-hospital mortality, assessed through Cox proportional hazard modeling. Secondary objectives were comparisons in the numbers of ventilator-free days (VFD) between day 1 and day 28 and between day 1 and 90 through competing risk regression. Results: Data from 1953 patients were included. After propensity score matching, 210 cases from each group were well matched. In the PS-matched cohort, mean (± SD) age was 60.3 ± 13.2 years and 296 (70.5%) were male and the most common comorbidities were hypertension (56.9%), obesity (41.1%), and diabetes (30.0%). The unadjusted hazard ratio (HR) for death at 90 days in the NMBA treatment vs control group was 1.12 (95% CI 0.79, 1.59, p = 0.534). After adjustment for smoking habit and critical therapeutic covariates, the HR was 1.07 (95% CI 0.72, 1.61, p = 0.729). At 28 days, VFD were 16 (IQR 0–25) and 25 (IQR 7–26) in the NMBA treatment and control groups, respectively (sub-hazard ratio 0.82, 95% CI 0.67, 1.00, p = 0.055). At 90 days, VFD were 77 (IQR 0–87) and 87 (IQR 0–88) (sub-hazard ratio 0.86 (95% CI 0.69, 1.07; p = 0.177). Conclusions: In patients with COVID-19 and moderate-to-severe ARDS, short course of NMBA treatment, applied early, did not significantly improve 90-day mortality and VFD. In the absence of definitive data from clinical trials, NMBAs should be indicated cautiously in this setting.

    DOI: 10.1186/s13054-022-03983-5

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  12. Correction to: Prognostic value of malnutrition evaluated using the Global Leadership Initiative on Malnutrition criteria and its association with psoas muscle volume in non-ischemic dilated cardiomyopathy.

    Ito R, Hiraiwa H, Araki T, Mizutani T, Kazama S, Kimura Y, Oishi H, Kuwayama T, Kondo T, Morimoto R, Okumura T, Murohara T

    Heart and vessels   Vol. 37 ( 12 ) page: 2013   2022.12

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    In the original publication of the article, the values of “Phenotypic criteria” were aligned incorrectly in Table 1. The correct Table 1 is provided below.

    DOI: 10.1007/s00380-022-02139-3

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  13. Prognostic value of malnutrition evaluated using the Global Leadership Initiative on Malnutrition criteria and its association with psoas muscle volume in non-ischemic dilated cardiomyopathy.

    Ito R, Hiraiwa H, Araki T, Mizutani T, Kazama S, Kimura Y, Oishi H, Kuwayama T, Kondo T, Morimoto R, Okumura T, Murohara T

    Heart and vessels   Vol. 37 ( 12 ) page: 2002 - 2012   2022.12

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    Heart failure (HF) is a systemic inflammatory disease that causes hypotrophy and skeletal muscle loss. The Global Leadership Initiative on Malnutrition (GLIM) criteria have been developed as a novel evaluation index for malnutrition, with reported usefulness in HF caused by ischemic heart disease. However, reports on the usefulness of malnutrition evaluated by the GLIM criteria in non-ischemic dilated cardiomyopathy (NIDCM) and its relationship with psoas muscle volume are lacking. We investigated the prognostic value of malnutrition evaluated using the GLIM criteria and its association with psoas muscle volume in patients with NIDCM. We enrolled 139 consecutive patients with NIDCM between December 2000 and June 2020. Malnutrition was evaluated using the GLIM criteria on admission. The median follow-up period was 4.7 years. Cardiac events were defined as a composite of cardiac death, hospitalization for worsening HF, and lethal arrhythmia. Furthermore, we measured the psoas muscle volume using computed tomography volumetry in 48 patients. At baseline, the median age was 50 years, and 132 patients (95.0%) had New York Heart Association functional class I or II HF. The median psoas muscle volume was 460.8 cm3. A total of 26 patients (18.7%) were malnourished according to the GLIM criteria. The Kaplan–Meier survival analysis showed that malnourished patients had more cardiac events than non-malnourished patients (log-rank, P < 0.001). The multivariate Cox proportional hazards regression analysis revealed that GLIM criteria-based malnutrition was an independent determinant of cardiac events (hazard ratio, 2.065; 95% confidence interval, 1.166–3.656; P = 0.014). Psoas muscle volume, which was assessed in a total of 48 patients, was lower in malnourished than in non-malnourished patients (median, 369.0 vs. 502.3 cm3; P = 0.035) and correlated with body mass index (r = 0.441; P = 0.002). Nutritional screening using the GLIM criteria may be useful in predicting future cardiac events in patients with NIDCM, reflecting a potential relationship between malnutrition and a low psoas muscle volume.

    DOI: 10.1007/s00380-022-02113-z

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  14. Benefits and Precautions in Using B-Type Natriuretic Peptide ― N-Terminal-Pro-B-Type Natriuretic Peptide Conversion Formula ―

    Okumura Takahiro, Hiraiwa Hiroaki, Takefuji Mikito, Murohara Toyoaki

    Circulation Journal   Vol. 86 ( 12 ) page: 2019 - 2020   2022.11

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    DOI: 10.1253/circj.CJ-22-0343

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  15. The cardiosplenic axis: the prognostic role of the spleen in heart failure.

    Hiraiwa H, Okumura T, Murohara T

    Heart failure reviews   Vol. 27 ( 6 ) page: 2005 - 2015   2022.11

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    Despite the number of available methods to predict prognosis in patients with heart failure, prognosis remains poor, likely because of marked patient heterogeneity and varied heart failure etiologies. Thus, identification of novel prognostic indicators to stratify risk in patients with heart failure is of paramount importance. The spleen is emerging as a potential novel prognostic indicator for heart failure. In this article, we provide an overview of the current prognostic tools used for heart failure. We then introduce the spleen as a potential novel prognostic indicator, before outlining the structure and function of the spleen and introducing the concept of the cardiosplenic axis. This is followed by a focused discussion on the function of the spleen in the immune response and in hemodynamics, as well as a review of what is known about the usefulness of the spleen as an indicator of heart failure. Expert insight into the most effective spleen-related measurement indices for the prognostication of patients with heart failure is provided, and suggestions on how these could be measured in clinical practice are considered. In future, studies in humans will be required to draw definitive links between specific splenic measurements and different heart failure manifestations, as well as to determine whether splenic prognostic measurements differ between heart failure classes and etiologies. These contributions will provide a step forward in our understanding of the usefulness of the spleen as a prognostic predictor in heart failure.

    DOI: 10.1007/s10741-022-10248-4

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  16. Methods for confirming the safety of radiation therapy in patients with left ventricular assist device: a case of extranodal NK/T-cell lymphoma, nasal type.

    Oishi H, Kondo T, Kawamura M, Shimada K, Mutsuga M, Kurokawa T, Kuwayama T, Hiraiwa H, Morimoto R, Okumura T, Nishida T, Kiyoi H, Naganawa S, Usui A, Murohara T

    Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs   Vol. 25 ( 3 ) page: 274 - 278   2022.9

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    A left ventricular assist device (LVAD) is a treatment option for patients with end-stage heart failure; however, a certain number of patients on durable LVADs are diagnosed with malignancy. Radiation therapy (RT) for patients with durable LVADs has safety concerns, because RT may interfere with the device. Herein, we report a case of RT during durable LVAD management. A 48-year-old man with a durable LVAD was diagnosed with sinusitis. As his symptoms were resistant to drug therapy, endoscopic sinus surgery was performed, and extranodal NK/T-cell lymphoma, nasal type (ENKL) was pathologically detected. Since RT was the first-line treatment for ENKL, we conducted two types of irradiation experiments to determine whether RT can be safely performed in patients with durable LVADs as follows: (1) assessing the extent of the radiation levels at each site and evaluating device malfunction by irradiating the lesion sites in the patient model with the same protocol as planned, and (2) evaluating device malfunction by directly irradiating the durable LVAD equipment once at the scheduled total dose. The radiation doses at the pump, driveline, system controller, power cable, and power module of the durable LVAD reached 7.86 cGy, 6.34 cGy, 0.66 cGy, 0.38 cGy, and 0.14 cGy, respectively. In both experiments, durable LVAD malfunction or any type of alarm was not observed. We concluded that RT could be safely performed with chemotherapy in this patient and our irradiation experiments can be applied to RT for other malignancies.

    DOI: 10.1007/s10047-022-01312-9

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  17. Splenic size as an indicator of hemodynamics and prognosis in patients with heart failure.

    Hiraiwa H, Okumura T, Sawamura A, Araki T, Mizutani T, Kazama S, Kimura Y, Shibata N, Oishi H, Kuwayama T, Kondo T, Furusawa K, Morimoto R, Murohara T

    Heart and vessels   Vol. 37 ( 8 ) page: 1344 - 1355   2022.8

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    The spleen is an important immune organ that releases erythrocytes and monocytes and destroys aged platelets. It also reserves 20–30% of the total blood volume, and its size decreases in hypovolemic shock. However, the clinical significance of splenic size in patients with heart failure (HF) remains unclear. We retrospectively analyzed the data of 206 patients with clinically stable HF gathered between January 2001 and August 2020 and recorded in a single-center registry. All patients underwent right heart catheterization and computed tomography (CT). Splenic size was measured using CT volumetry. The primary outcomes were composite cardiac events occurring for the first time during follow-up, namely, cardiac death and hospitalization for worsening HF. The median splenic volume and splenic volume index (SVI) were 118.0 mL and 68.9 mL/m2, respectively. SVI was positively correlated with cardiac output (r = 0.269, P < 0.001) and stroke volume (r = 0.228, P = 0.002), and negatively correlated with systemic vascular resistance (r = − 0.302, P < 0.001). Seventy cardiac events occurred, and the optimal receiver operating characteristic curve SVI cutoff value for predicting cardiac events was 68.9 mL/m2. The median blood adrenaline concentration was higher in the low-SVI group than the high-SVI group (0.039 ng/mL vs. 0.026 ng/mL, respectively; P = 0.004), and the low-SVI group experienced more cardiac events (log-rank test, P < 0.001). Multivariate Cox proportional hazards regression revealed that a low SVI was an independent predictor of cardiac events, even when adjusted for the validated HF risk score, blood–brain natriuretic peptide concentration, blood catecholamine concentrations, and hemodynamic parameters. Splenic size reflects hemodynamics, including systemic circulating blood volume status and sympathetic nerve activity, and is associated with HF prognosis.

    DOI: 10.1007/s00380-022-02030-1

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  18. Clinical value of the HATCH score for predicting adverse outcomes in patients with heart failure.

    Shibata N, Kondo T, Morimoto R, Kazama S, Sawamura A, Nishiyama I, Kato T, Kuwayama T, Hiraiwa H, Umemoto N, Asai T, Okumura T, Murohara T

    Heart and vessels   Vol. 37 ( 8 ) page: 1363 - 1372   2022.8

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    The HATCH score is employed as a risk assessment tool for atrial fibrillation (AF) development. However, the impact of the HATCH score on the long-term adverse outcomes in patients with acute heart failure (AHF) remains unknown. We investigated the clinical value of the HATCH score in patients with AHF. From a multicenter AHF registry, we retrospectively evaluated 1543 consecutive patients who required hospitalization owing to AHF (median age, 78 [69–85] years; 42.3% women) from January 2012 to December 2019. These patients were divided into five risk groups based on their HATCH score at admission (scores 0, 1, 2, 3, and 4–7). The correlation between the HATCH score and the composite outcome, including all-cause mortality and re-hospitalization due to HF, was analyzed using Kaplan–Meier and Cox proportional-hazard analyses. The median HATCH score was 2 [1–3], and the median age was 78 years (69–85 years). During the follow-up period (median, 16.8 months), the composite endpoint occurred in 691 patients (44.8%), including 416 (27%) patients who died (with 65 [4.2%] in-hospitalization deaths) and 455 (29.5%) patients requiring re-hospitalizations due to HF. The Kaplan–Meier analysis showed a significant increase in the composite endpoint with an increasing HATCH score (log-rank, p < 0.001). The multivariate Cox regression model revealed that the HATCH score was an independent predictor of the composite endpoint (hazard ratio [HR] 1.181; 95% confidence interval [CI]: 1.111–1.255; p < 0.001) with all-cause mortality (HR 1.153, 95% CI 1.065–1.249; p < 0.001) and re-hospitalizations due to HF (HR 1.21; 95% CI 1.124–1.303; p < 0.001) in patients with AHF, regardless of the presence or absence of AF, ejection fraction, and etiology. The HATCH score is an independent predictor of adverse outcomes in patients with AHF.

    DOI: 10.1007/s00380-022-02035-w

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  19. ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19

    Garcia-Gallo E., Merson L., Kennon K., Kelly S., Citarella B.W., Fryer D.V., Shrapnel S., Lee J., Duque S., Fuentes Y.V., Balan V., Smith S., Wei J., Gonçalves B.P., Russell C.D., Sigfrid L., Dagens A., Olliaro P.L., Baruch J., Kartsonaki C., Dunning J., Rojek A., Rashan A., Beane A., Murthy S., Reyes L.F., Abbas A., Abdukahil S.A., Abdulkadir N.N., Abe R., Abel L., Absil L., Jabal K.A., Zayyad H.A., Acharya S., Acker A., Adachi S., Adam E., Adriano E., Adrião D., Ageel S.A., Ahmed S., Aiello M., Ainscough K., Airlangga E., Aisa T., Hssain A.A., Tamlihat Y.A., Akimoto T., Akmal E., Qasim E.A., Al-Dabbous T., Al-Fares A., Alalqam R., Alberti A., Alegesan S., Alegre C., Alessi M., Alex B., Alexandre K., Alfoudri H., Ali A., Ali I., Shah N.A., Sheikh N.A., Alidjnou K.E., Aliudin J., Alkhafajee Q., Allavena C., Allou N., Altaf A., Alves J., Alves J.M., Alves R., Amaral M., Amira N., Ammerlaan H., Ampaw P., Andini R., Andrejak C., Angheben A., Angoulvant F., Ansart S., Anthonidass S., Antonelli M., Antunes de Brito C.A., Anwar K.R., Apriyana A., Arabi Y., Aragao I., Arancibia F., Araujo C., Arcadipane A., Archambault P., Arenz L., Arlet J.B., Arnold-Day C., Aroca A., Arora L., Arora R.

    Scientific Data   Vol. 9 ( 1 )   2022.7

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    The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.

    DOI: 10.1038/s41597-022-01534-9

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  20. Clinical Effect of Pulmonary Artery Diameter/Ascending Aorta Diameter Ratio on Left Ventricular Reverse Remodeling in Patients With Dilated Cardiomyopathy

    Shibata Naoki, Hiraiwa Hiroaki, Kazama Shingo, Kimura Yuki, Araki Takashi, Mizutani Takashi, Oishi Hideo, Kuwayama Tasuku, Kondo Toru, Morimoto Ryota, Okumura Takahiro, Murohara Toyoaki

    Circulation Journal   Vol. 86 ( 7 ) page: 1102 - 1112   2022.6

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    <p><b><i>Background:</i></b> Many patients with dilated cardiomyopathy (DCM) progress to heart failure (HF), although some demonstrate left ventricular (LV) reverse remodeling (LVRR), which is associated with better outcomes. The pulmonary artery diameter (PAD) to ascending aortic diameter (AoD) ratio has been used as a prognostic predictor in patients with HF, although this tool’s usefulness in predicting LVRR remains unknown.</p><p><b><i>Methods and Results:</i></b> Data from a prospective observational study of 211 patients diagnosed in 2000–2020 with DCM were retrospectively analyzed. Sixty-nine patients with New York Heart Association class I or II HF were included. LVRR was observed in 23 patients (33.3%). The mean LV ejection fraction (29%) and LV end-diastolic dimension (64.5 mm) were similar in patients with and without LVRR. The PAD/AoD ratio was significantly lower in patients with LVRR than those without (81.4% vs. 92.4%, respectively; P=0.003). The optimal PAD/AoD cut-off value for detecting LVRR was 0.9 according to the receiver operating characteristic curve analysis. Multivariate analysis identified a PAD/AoD ratio ≥0.9 as an independent predictor of presence/absence of LVRR. Cardiac events were significantly more common in patients with a PAD/AoD ratio ≥0.9 than those with a ratio <0.9, after a median follow up of 2.5 years (log-rank, P=0.007).</p><p><b><i>Conclusions:</i></b> The PAD/AoD ratio can predict LVRR in patients with DCM.</p>

    DOI: 10.1253/circj.CJ-21-0786

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  21. Flexion limitation of the Impella 5.0 when implanted using the femoral approach in patients with small stature.

    Hiraiwa H, Kimura Y, Morimoto R, Ito R, Araki T, Mizutani T, Kazama S, Oishi H, Kuwayama T, Kondo T, Furusawa K, Okumura T, Mutsuga M, Usui A, Murohara T

    Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs   Vol. 25 ( 2 ) page: 182 - 183   2022.6

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    DOI: 10.1007/s10047-022-01311-w

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  22. Impella5.0 "ILIPELLA" Approach for a Fulminant Myocarditis Patient With a Small Peripheral Artery.

    Mutsuga M, Banno H, Okumura T, Morimoto R, Kondo T, Kimura Y, Hiraiwa H, Murohara T, Usui A

    Heart, lung & circulation   Vol. 31 ( 5 ) page: e72 - e74   2022.5

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    Cardiogenic shock with fulminant myocarditis is a life-threatening diagnosis. Extracorporeal membrane oxygenation (ECMO) with an Impella for left ventricle unloading is often required to maintain the haemodynamics. However, the small peripheral vascularity in small-bodied patients interrupts the upgrade from ECMO to Impella5.0, which usually requires grafting to a femoral artery or subclavian artery of at least 7 mm in size. This report outlines the external iliac artery approach, named the “ILIPELLA” technique, which uses a reconstructed external iliac artery to introduce Impella5.0 in patients with small peripheral vascularity.

    DOI: 10.1016/j.hlc.2021.12.007

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  23. Serum autotaxin as a novel prognostic marker in patients with non-ischaemic dilated cardiomyopathy.

    Araki T, Okumura T, Hiraiwa H, Mizutani T, Kimura Y, Kazama S, Shibata N, Oishi H, Kuwayama T, Kondo T, Morimoto R, Takefuji M, Murohara T

    ESC heart failure   Vol. 9 ( 2 ) page: 1304 - 1313   2022.4

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    Aims: Autotaxin (ATX) promotes myocardial inflammation, fibrosis, and the subsequent cardiac remodelling through lysophosphatidic acid production. However, the prognostic impact of serum ATX in non-ischaemic dilated cardiomyopathy (NIDCM) has not been clarified. We investigated the prognostic impact of serum ATX in patients with NIDCM. Methods and results: We enrolled 104 patients with NIDCM (49.8 ± 13.4 years, 76 men). We divided the patients into two groups using different cutoffs of median serum ATX levels for men and women: high-ATX group and low-ATX group. Cardiac events were defined as a composite of cardiac death and heart failure resulting in hospitalization. Median ATX level was 203.5 ng/mL for men and 257.0 ng/mL for women. Brain natriuretic peptide levels [224.0 (59.6–689.5) pg/mL vs. 96.5 (40.8–191.5) pg/mL, P = 0.010] were higher in the high-ATX group than low-ATX group, whereas high-sensitivity C-reactive protein and collagen volume fraction levels in endomyocardial biopsy samples were not significantly different between the two groups. Kaplan–Meier survival analysis revealed that the event-free survival rate was significantly lower in the high-ATX group than low-ATX group (log-rank; P = 0.007). Cox proportional hazard analysis revealed that high-ATX was an independent determinant of composite cardiac events. In both sexes, serum ATX levels did not correlate with high-sensitivity C-reactive protein levels and collagen volume fraction but had a weak correlation with brain natriuretic peptide levels (men; spearman's rank: 0.274, P = 0.017, women; spearman's rank: 0.378, P = 0.048). Conclusion: High serum ATX levels can be associated with increasing adverse clinical outcomes in patients with NIDCM. These results indicate serum ATX may be a novel biomarker or therapeutic target in NIDCM.

    DOI: 10.1002/ehf2.13817

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  24. A Case of Systemic Capillary Leak Syndrome with Severe Cardiac Dysfunction after mRNA Vaccination for COVID-19.

    Araki T, Morimoto R, Ito R, Mizutani T, Kimura Y, Kazama S, Oishi H, Kuwayama T, Hiraiwa H, Kondo T, Okumura T, Murohara T

    CJC open     2022.3

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    DOI: 10.1016/j.cjco.2022.03.008

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  25. Relationship between spleen size and exercise tolerance in advanced heart failure patients with a left ventricular assist device.

    Hiraiwa H, Okumura T, Sawamura A, Araki T, Mizutani T, Kazama S, Kimura Y, Shibata N, Oishi H, Kuwayama T, Kondo T, Furusawa K, Morimoto R, Adachi T, Yamada S, Mutsuga M, Usui A, Murohara T

    BMC research notes   Vol. 15 ( 1 ) page: 40   2022.2

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    Objective: Spleen volume increases in patients with advanced heart failure (HF) after left ventricular assist device (LVAD) implantation. However, the relationship between spleen volume and exercise tolerance (peak oxygen consumption [VO2]) in these patients remains unknown. In this exploratory study, we enrolled 27 patients with HF using a LVAD (median age: 46 years). Patients underwent blood testing, echocardiography, right heart catheterization, computed tomography (CT), and cardiopulmonary exercise testing. Spleen size was measured using CT volumetry, and the correlations/causal relationships of factors affecting peak VO2 were identified using structural equation modeling. Results: The median spleen volume was 190.0 mL, and peak VO2 was 13.2 mL/kg/min. The factors affecting peak VO2 were peak heart rate (HR; β = 0.402, P =.015), pulmonary capillary wedge pressure (PCWP; β = − 0.698, P =.014), right ventricular stroke work index (β = 0.533, P =.001), blood hemoglobin concentration (β = 0.359, P =.007), and spleen volume (β = 0.215, P =.041). Spleen volume correlated with peak HR, PCWP, and hemoglobin concentration, reflecting sympathetic activity, cardiac preload, and oxygen-carrying capacity, respectively, and was thus related to peak VO2. These results suggest an association between spleen volume and exercise tolerance in advanced HF.

    DOI: 10.1186/s13104-022-05939-y

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  26. Recurrent fulminant non-rheumatic streptococcal myocarditis proven by endomyocardial biopsy and autopsy

    Hiraiwa H., Morimoto R., Ando R., Ito R., Araki T., Mizutani T., Kazama S., Kimura Y., Oishi H., Kuwayama T., Yamaguchi S., Kondo T., Okumura T., Enomoto A., Murohara T.

    Journal of Cardiology Cases     2022

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    A 42-year-old man with a history of acute myocarditis after streptococcal pharyngitis developed recurrent fulminant myocarditis. Endomyocardial biopsy revealed myocyte degeneration, interstitial edema, and neutrophil infiltration. The patient's cardiac function deteriorated rapidly, and he died despite mechanical circulatory support. Autopsy revealed neutrophil infiltration, interstitial edema, and micro-abscesses containing masses of streptococci and neutrophilic phagocytosis within the myocardium. The patient did not meet the diagnostic criteria for acute rheumatic fever; thus, he was diagnosed with non-rheumatic streptococcal myocarditis. Non-rheumatic streptococcal myocarditis rarely recurs, but it can be fulminant upon recurrence. Learning objective: We report a rare case of recurrent fulminant non-rheumatic streptococcal myocarditis. Endomyocardial biopsy and autopsy revealed neutrophil infiltration and micro-abscesses containing bacterial masses of streptococci and neutrophilic phagocytosis in the myocardium. The patient did not meet the diagnostic criteria for acute rheumatic fever; thus, he was diagnosed with non-rheumatic streptococcal myocarditis. Non-rheumatic streptococcal myocarditis rarely recurs, but it can be fulminant upon recurrence.

    DOI: 10.1016/j.jccase.2022.02.004

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  27. Prognostic impact of transcardiac gradient of follistatin-like 1 reflecting hemodynamics in patients with dilated cardiomyopathy.

    Oishi H, Okumura T, Ohashi K, Kimura Y, Kazama S, Shibata N, Arao Y, Kato H, Kuwayama T, Yamaguchi S, Tatsumi M, Kondo T, Hiraiwa H, Morimoto R, Takefuji M, Ouchi N, Murohara T

    Journal of cardiology   Vol. 78 ( 6 ) page: 524 - 532   2021.12

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    Background: Follistatin-like 1 (FSTL1) is a myocyte-secreted glycoprotein that could play a role in myocardial maintenance in response to harmful stimuli. We investigated the association between serum FSTL1 levels, especially focused on transcardiac gradient and the hemodynamics, to explore the prognostic impact of FSTL1 levels in patients with dilated cardiomyopathy (DCM). Methods: Thirty-two ambulatory patients with DCM (23 men; mean age 59 years) were prospectively enrolled. Blood samples were simultaneously collected from the aortic root (Ao), coronary sinus (CS), as well as from the peripheral vein during cardiac catheterization in stable conditions. The transcardiac gradient of FSTL1 was calculated by the difference between serum FSTL1 levels of CS and Ao (FSTL1CS-Ao). Patients were divided into two groups based on the median of FSTL1CS-Ao: Low FSTL1CS-Ao group, <0 ng/mL; High FSTL1CS-Ao group, ≥0 ng/mL. Cardiac events were defined as a composite of cardiac deaths and hospitalizations for worsening heart failure. Results: Mean left ventricular ejection fraction and median plasma B-type natriuretic peptide levels were 30.9% and 92.3 pg/mL, respectively. FSTL1CS-Ao was negatively correlated with pulmonary capillary wedge pressure (r = -0.400, p = 0.023). Kaplan-Meier survival analysis showed that event-free survival rate was significantly lower in the Low FSTL1CS-Ao group than in the High FSTL1CS-Ao group (p = 0.013). Cox regression analyses revealed that the transcardiac gradient of FSTL1 was an independent predictor for cardiac events. Receiver operating characteristic curve analysis showed that the cut-off value of FSTL1CS-Ao for the prediction of cardiac events was -4.09 ng/mL with sensitivity of 82% and specificity of 86% (area under the curve, 0.87). Conclusions: Fifty percent of patients had negative transcardiac gradient of FSTL1. Reduced transcardiac gradient of FSTL1 might be a novel prognostic predictor in DCM patients with impaired hemodynamics.

    DOI: 10.1016/j.jjcc.2021.07.005

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  28. Comparison of Impella 5.0 and extracorporeal left ventricular assist device in patients with cardiogenic shock.

    Kondo T, Morimoto R, Mutsuga M, Fujimoto K, Okumura T, Shibata N, Kazama S, Kimira Y, Oishi H, Kuwayama T, Hiraiwa H, Usui A, Murohara T

    The International journal of artificial organs   Vol. 44 ( 11 ) page: 846 - 853   2021.11

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    Introduction: Choice of mechanical circulatory support to stabilize hemodynamics until cardiac recovery or next treatment is a strategic cornerstone for improving outcomes in patients with severe cardiogenic shock. We aimed to clarify the difference in treatment course and outcomes with the use of Impella 5.0 and an extracorporeal left ventricular assist device (eLVAD) in patients with cardiogenic shock refractory to medical therapy or other mechanical circulatory support. Methods: We performed a retrospective medical record review of consecutive patients who were implanted with Impella 5.0 or eLVAD as a bridge to decision at our medical center. Results: A total of 26 patients (median age 40 years, 16 males) were analyzed. Of seven patients managed with Impella 5.0, the Impella 5.0 was removed successfully in two patients and five patients underwent surgery for durable LVAD implantation. Of 19 patients managed with eLVAD, the eLVAD was successfully removed in 3 patients, 9 patients required durable LVAD, and 7 patients died during eLVAD management. The period between Impella 5.0 or eLVAD implantation to durable LVAD surgery was significantly shorter with Impella 5.0 (58 vs 235 days, p = 0.001). Cardiopulmonary bypass time was significantly shorter and a significantly smaller amount of red blood cell transfusion was required with Impella 5.0 (149 vs 192 min, p = 0.042; 7.0 vs 15.0 units, p = 0.019). There were four massive stroke events with eLVAD, but no massive stroke event with Impella 5.0. Conclusion: Impella 5.0 facilitates smoother management as a bridge to decision and reduces surgical invasiveness during durable LVAD implantation.

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  29. The protective effect of tight-fitting powered air-purifying respirators during chest compressions.

    Goto Y, Jingushi N, Hiraiwa H, Ogawa H, Sakai Y, Kasugai D, Tanaka T, Higashi M, Yamamoto T, Numaguchi A

    The American journal of emergency medicine   Vol. 49   page: 172 - 177   2021.11

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    Background: Airborne personal protective equipment is required for healthcare workers when performing aerosol-generating procedures on patients with infectious diseases. Chest compressions, one of the main components of cardiopulmonary resuscitation, require intense and dynamic movements of the upper body. We aimed to investigate the protective effect of tight-fitting powered air-purifying respirators (PAPRs) during chest compressions. Methods: This single-center simulation study was performed from February 2021 to March 2021. The simulated workplace protection factor (SWPF) is the concentration ratio of ambient particles and particles inside the PAPR mask; this value indicates the level of protection provided by a respirator when subjected to a simulated work environment. Participants performed continuous chest compressions three times for 2 min each time, with a 4-min break between each session. We measured the SWPF of the tight-fitting PAPR during chest compression in real-time mode. The primary outcome was the ratio of any failure of protection (SWPF <500) during the chest compression sessions. Results: Fifty-four participants completed the simulation. Overall, 78% (n = 42) of the participants failed (the measured SWPF value was less than 500) at least one of the three sessions of chest compressions. The median value and interquartile range of the SWPF was 4304 (685–16,191). There were no reports of slipping down of the respirator or mechanical failure during chest compressions. Conclusions: Although the median SWPF value was high during chest compressions, the tight-fitting PAPR did not provide adequate protection.

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  30. Clinical impact of visually assessed right ventricular dysfunction in patients with septic shock.

    Hiraiwa H, Kasugai D, Ozaki M, Goto Y, Jingushi N, Higashi M, Nishida K, Kondo T, Furusawa K, Morimoto R, Okumura T, Matsuda N, Matsui S, Murohara T

    Scientific reports   Vol. 11 ( 1 ) page: 18823   2021.9

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    We retrospectively analyzed data from the Medical Information Mart for Intensive Care-III critical care database to determine whether visually-assessed right ventricular (RV) dysfunction was associated with clinical outcomes in septic shock patients. Associations between visually-assessed RV dysfunction by echocardiography and in-hospital mortality, lethal arrhythmia, and hemodynamic indicators to determine the prognostic value of RV dysfunction in patients with septic shock were analyzed. Propensity score analysis showed RV dysfunction was associated with increased risk of in-hospital death in patients with septic shock (adjusted odds ratio [OR] 2.15; 95% confidence interval [CI] 1.99–2.32; P < 0.001). In multivariate logistic regression analysis, RV dysfunction was associated with in-hospital death (OR 2.19; 95% CI 1.91–2.53; P < 0.001), lethal arrhythmia (OR 2.19; 95% CI 1.34–3.57; P < 0.001), and tendency for increased blood lactate levels (OR 1.31; 95% CI 1.14–1.50; P < 0.001) independent of left ventricular (LV) dysfunction. RV dysfunction was associated with lower cardiac output, pulmonary artery pressure index, and RV stroke work index. In patients with septic shock, visually-assessed RV dysfunction was associated with in-hospital mortality, lethal arrhythmia, and circulatory insufficiency independent of LV dysfunction. Visual assessment of RV dysfunction using echocardiography might help to identify the short-term prognosis of patients with septic shock by reflecting hemodynamic status.

    DOI: 10.1038/s41598-021-98397-8

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  31. Clinical impact of heart rate change in patients with acute heart failure in the early phase.

    Kazama S, Kondo T, Shibata N, Hiraiwa H, Nishiyama I, Kato T, Sawamura A, Kimura Y, Oishi H, Kuwayama T, Morimoto R, Okumura T, Shimizu K, Murohara T

    ESC heart failure   Vol. 8 ( 4 ) page: 2982 - 2990   2021.8

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    Aims: Patients with acute heart failure (AHF) often present with an increased heart rate (HR), and the HR changes dramatically after initial treatment for AHF. However, the HR change after admission and the relationship between HR change in the early phase and prognosis have not been fully elucidated. Methods and results: From a multicentre AHF registry, we retrospectively evaluated 1527 consecutive patients admitted with AHF. HR change (%) was calculated by [HR (at admission) − HR (24 h after admission)] × 100∕HR (at admission). The median HR change was 15.1% (range, 2.0–28.4%). The HR decreased most in the first 24 h and then gradually thereafter [admission: 98 (81–117) b.p.m., 24 h: 80 (70–92) b.p.m., 48 h: 78 (68–90) b.p.m., and 72 h: 77 (67–88) b.p.m.]. In Kaplan–Meier analysis, the cumulative event-free rates in the composite endpoint of death and rehospitalization due to AHF showed better according to larger HR change (P = 0.012, log rank). Cox proportional hazards analysis showed that HR change was a prognostic factor for composite endpoint adjusted by age and sex [hazard ratio, 0.995; 95% confidence interval (CI), 0.991–0.998; P = 0.006]. HR change was associated with outcome adjusted by age and sex in patients with sinus rhythm (hazard ratio, 0.993; 95% CI, 0.988–0.999; P = 0.015), but not in patients with atrial fibrillation (hazard ratio, 0.996; 95% CI, 0.990–1.002; P = 0.15). Conclusions: A decrease in HR in the first 24 h after admission indicates better prognosis in patients with AHF, although the prognostic influence may differ between patients with sinus rhythm and those with atrial fibrillation.

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  32. Prognostic value of resting cardiac power index depends on mean arterial pressure in dilated cardiomyopathy.

    Morimoto R, Mizutani T, Araki T, Oishi H, Kimura Y, Kazama S, Shibata N, Kuwayama T, Hiraiwa H, Kondo T, Furusawa K, Okumura T, Murohara T

    ESC heart failure   Vol. 8 ( 4 ) page: 3206 - 3213   2021.8

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    Aims: In recent decades, haemodynamic parameters have been estimated for risk stratification and determining treatment strategies for patients with non-ischaemic dilated cardiomyopathy (DCM). In various invasive procedures, the cardiac pumping capability is defined as cardiac power output (CPO), which is calculated by multiplying cardiac output by the mean arterial pressure. Lower CPO values in advanced heart failure predict adverse outcomes. However, few studies discuss the prognostic value of CPO in mild-to-moderate phase patients. This study aimed to determine the value of the cardiac power index (CPI) obtained from the resting CPO for predicting the prognosis of patients with New York Heart Association Functional Class II or III DCM. Methods and results: From March 2000 to January 2020, a total of 623 cardiomyopathy patients were evaluated for haemodynamic parameters. Patients with secondary cardiomyopathy, ischaemic cardiomyopathy, valvular heart disease, and Class IV cardiomyopathy were excluded. A total of 176 DCM patients fulfilled the criteria for inclusion. Patients were 51.7 ± 12.5 years old (mean ± standard deviation) with a mean left ventricular ejection fraction of 32.1 ± 9.2%. The patients were divided into two groups by their median CPI (CPI < 0.52, low-CPI; CPI ≥ 0.52, high-CPI). No significant differences were found in the left ventricular end-diastolic diameter, left ventricular ejection fraction, or pulmonary arterial wedge pressure between the groups. The probability of cardiac event-free survival was significantly lower for low-CPI than for high-CPI groups by Kaplan–Meier analysis (P = 0.012), even with no significant difference between the high and low cardiac index groups (P = 0.069). Furthermore, Cox proportional hazards regression analysis revealed that, in addition to the CPI, the systolic and mean arterial pressure involved in CPI calculation were independent predictors of cardiac events. Indeed, among these factors, mean arterial pressure had the strongest prognostic ability. Conclusions: Although CPI is effective for stratifying DCM and predicting cardiac events in patients with Class II/III DCM, this prognostic value depends on mean arterial pressure.

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  33. Prognostic impact of immune-related adverse events on patients with and without cardiovascular disease: a retrospective review.

    Kazama S, Morimoto R, Kimura Y, Shibata N, Ozaki R, Araki T, Mizutani T, Oishi H, Arao Y, Kuwayama T, Hiraiwa H, Kondo T, Furusawa K, Shimokata T, Okumura T, Bando YK, Ando Y, Murohara T

    Cardio-oncology (London, England)   Vol. 7 ( 1 ) page: 26   2021.7

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    Background: The emergence of immune checkpoint inhibitors (ICIs) has brought about a paradigm shift in cancer treatment as the use of these drugs has become more frequent and for a longer duration. As a result of T-cell-mediated inflammation at the programmed cell death-1, programmed death-ligand-1, and cytotoxic T-lymphocyte antigen-4 pathways, immune-related adverse events (irAEs) occur in various organs and can cause a rare but potentially induced cardiotoxicity. Although irAEs are associated with the efficacy of ICI therapy and better prognosis, there is limited information about the correlation between irAEs and cardiotoxicity and whether the benefits of irAEs apply to patients with underlying cardiovascular disease. This study aimed to investigate the association of irAEs and treatment efficacy in patients undergoing ICI therapy with and without a cardiovascular history. Methods: We performed a retrospective review of the medical records of 409 consecutive patients who received ICI therapy from September 2014 to October 2019. Results: Median patient age was 69 years (29.6% were female). The median follow-up period was 278 days. In total, 69 (16.9%) patients had a history of any cardiovascular disease and 14 (3.4%) patients experienced cardiovascular irAEs after ICI administration. The rate of cardiovascular irAEs was higher in patients with prior non-cardiovascular irAEs than without. The prognosis of patients with irAEs (+) was significantly better than that of the patients without irAEs (P < 0.001); additionally, this tendency did not depend on the presence or absence of a cardiovascular history. Furthermore, the Cox proportional hazards analysis revealed that irAEs were an independent predictor of mortality. Conclusions: Although cardiovascular irAEs may be related to prior non-cardiovascular irAEs under ICI therapy, the occurrence of irAEs had a better prognostic impact and this tendency was not affected by cardiovascular history.

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  34. Prognostic value of leucine/phenylalanine ratio as an amino acid profile of heart failure.

    Hiraiwa H, Okumura T, Kondo T, Kato T, Kazama S, Kimura Y, Ishihara T, Iwata E, Shimojo M, Kondo S, Aoki S, Kanzaki Y, Tanimura D, Sano H, Awaji Y, Yamada S, Murohara T

    Heart and vessels   Vol. 36 ( 7 ) page: 965 - 977   2021.7

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    Heart failure (HF) causes a hypercatabolic state that enhances the catabolic activity of branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in the heart and skeletal muscles and reduces protein synthesis in the liver. Consequently, free plasma aromatic amino acids (AAA, tyrosine and phenylalanine) are increased. To date, we have reported the prognostic value of the BCAA/AAA ratio (Fischer’s ratio) in patients with HF. However, the leucine/phenylalanine ratio, which is a simpler index than the Fischer’s ratio, has not been examined. Therefore, the prognostic value of the leucine/phenylalanine ratio in patients with HF was investigated. Overall 157 consecutive patients hospitalized for worsening HF (81 men, median age 78 years) were enrolled in the study. Plasma amino acid levels were measured when the patients were stabilized at discharge. Cardiac events were defined as a composite of cardiac death and hospitalization for worsening HF. A total of 46 cardiac events occurred during the median follow-up period of 238 (interquartile range 93–365) days. The median leucine/phenylalanine ratio was significantly lower in patients with cardiac events than in those without cardiac events (1.4 vs. 1.8, P < 0.001). The best cutoff value of the leucine/phenylalanine ratio was determined as 1.7 in the receiver operating characteristic (ROC) curve for cardiac events. Following a Kaplan–Meier survival analysis, the low group (leucine/phenylalanine ratio < 1.7, n = 72) had more cardiac events than the high group (leucine/phenylalanine ratio ≥ 1.7, n = 85) (log-rank, P < 0.001). Multivariate Cox proportional hazards regression analysis showed that the leucine/phenylalanine ratio was an independent predictor of cardiac events. Furthermore, on comparing the prognostic values for cardiac events based on ROC curves of leucine levels, BCAA levels, Fischer’s ratio, and leucine/phenylalanine ratio, the leucine/phenylalanine ratio was the most accurate in predicting future cardiac events (area under the curve 0.763,; sensitivity 0.783,; specificity 0.676,; P < 0.001). The leucine/phenylalanine ratio could be a useful predictor of future cardiac events in patients with HF, reflecting an imbalance in amino acid metabolism.

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  35. Usefulness of Respiratory Mechanics and Laboratory Parameter Trends as Markers of Early Treatment Success in Mechanically Ventilated Severe Coronavirus Disease: A Single-Center Pilot Study.

    Kasugai D, Ozaki M, Nishida K, Hiraiwa H, Jingushi N, Numaguchi A, Omote N, Shindo Y, Goto Y

    Journal of clinical medicine   Vol. 10 ( 11 )   2021.6

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    Whether a patient with severe coronavirus disease (COVID-19) will be successfully liberated from mechanical ventilation (MV) early is important in the COVID-19 pandemic. This study aimed to characterize the time course of parameters and outcomes of severe COVID-19 in relation to the timing of liberation from MV. This retrospective, single-center, observational study was performed using data from mechanically ventilated COVID-19 patients admitted to the ICU between 1 March 2020 and 15 December 2020. Early liberation from ventilation (EL group) was defined as successful extubation within 10 days of MV. The trends of respiratory mechanics and laboratory data were visualized and compared between the EL and prolonged MV (PMV) groups using smoothing spline and linear mixed effect models. Of 52 admitted patients, 31 mechanically ventilated COVID-19 patients were included (EL group, 20 (69%); PMV group, 11 (31%)). The patients’ median age was 71 years. While in-hospital mortality was low (6%), activities of daily living (ADL) at the time of hospital discharge were significantly impaired in the PMV group compared to the EL group (mean Barthel index (range): 30 (7.5–95) versus 2.5 (0–22.5), p = 0.048). The trends in respiratory compliance were different between patients in the EL and PMV groups. An increasing trend in the ventilatory ratio during MV until approximately 2 weeks was observed in both groups. The interaction between daily change and earlier liberation was significant in the trajectory of the thrombin–antithrombin complex, antithrombin 3, fibrinogen, C-reactive protein, lymphocyte, and positive end-expiratory pressure (PEEP) values. The indicator of physiological dead space increases during MV. The trajectory of markers of the hypercoagulation status, inflammation, and PEEP were significantly different depending on the timing of liberation from MV. These findings may provide insight into the pathophysiology of COVID-19 during treatment in the critical care setting.

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  36. A clinical score for predicting left ventricular reverse remodelling in patients with dilated cardiomyopathy.

    Kimura Y, Okumura T, Morimoto R, Kazama S, Shibata N, Oishi H, Araki T, Mizutani T, Kuwayama T, Hiraiwa H, Kondo T, Murohara T

    ESC heart failure   Vol. 8 ( 2 ) page: 1359 - 1368   2021.4

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    Aims: Left ventricular reverse remodelling (LVRR) is a well-established predictor of a good prognosis in patients with dilated cardiomyopathy (DCM). The prediction of LVRR is important when developing a long-term treatment strategy. This study aimed to assess the clinical predictors of LVRR and establish a scoring system for predicting LVRR in patients with DCM that can be used at any institution. Methods and results: We consecutively enrolled 131 patients with DCM and assessed the clinical predictors of LVRR. LVRR was defined as an absolute increase in left ventricular ejection fraction (LVEF) from ≥10% to a final value of >35%, accompanied by a decrease in left ventricular end-diastolic dimension (LVEDD) ≥ 10% on echocardiography at 1 ± 0.5 years after a diagnosis of DCM. The mean patient age was 50.1 ± 11.9 years. The mean LVEF was 32.2 ± 9.5%, and the mean LVEDD was 64.1 ± 12.5 mm at diagnosis. LVRR was observed in 45 patients (34%) at 1 ± 0.5 years. In a multivariate analysis, hypertension [odds ratio (OR): 6.86; P = 0.002], no family history of DCM (OR: 10.45; P = 0.037), symptom duration <90 days (OR: 6.72; P < 0.001), LVEF <35% (OR: 13.66; P < 0.0001), and QRS duration <116 ms (OR: 5.94; P = 0.005) were found to be independent predictors of LVRR. We scored the five independent predictors according to the ORs (1 point, 2 points, 1 point, 2 points, and 1 point, respectively), and the total LVRR predicting score was calculated by adding these scores. The LVRR rate was stratified by the LVRR predicting score (0–2 points: 0%; 3 points: 6.7%; 4 points: 17.4%; 5 points: 48.2%; 6 points: 79.2%; and 7 points: 100%). The cut-off value of the LVRR predicting score was >5 in receiver-operating characteristic curve analysis (area under the curve: 0.89; P < 0.0001; sensitivity: 87%; specificity: 78%). An LVRR predicting score of >5 was an independent predictor compared with the presence of late gadolinium enhancement on cardiovascular magnetic resonance or the severity of fibrosis on endomyocardial biopsy (OR: 11.79; 95% confidence interval: 2.40–58.00; P = 0.002). Conclusions: The LVRR predicting score using five predictors including hypertension, no family history of DCM, symptom duration <90 days, LVEF <35%, and QRS duration <116 ms can stratify the LVRR rate in patients with DCM. The LVRR predicting score may be a useful clinical tool that can be used easily at any institution.

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  37. Association between splenic volume and pulsatility index in patients with left ventricular assist devices.

    Hiraiwa H, Okumura T, Sawamura A, Kondo T, Kazama S, Kimura Y, Shibata N, Arao Y, Oishi H, Kato H, Kuwayama T, Yamaguchi S, Furusawa K, Morimoto R, Fujimoto K, Mutsuga M, Usui A, Murohara T

    The International journal of artificial organs   Vol. 44 ( 4 ) page: 282 - 287   2021.4

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    The spleen serves as a blood volume reservoir for systemic volume regulation in heart failure (HF) patients. Changes are seen in spleen size in advanced HF patients after left ventricular assist device (LVAD) implantation. The pulsatility index (PI) is an indicator of native heart contractility with hemodynamic changes in patients using LVAD. We hypothesized that the splenic volume was associated with the PI, reflecting the hemodynamics in advanced HF patients with LVADs. Herein, we investigated the relationship between splenic volume and PI in these patients. Forty-four patients with advanced HF underwent implantation of HeartMate II® (Abbott, Chicago, IL, USA) as a bridge to heart transplantation at the Nagoya University Hospital between October 2013 and June 2019. The data of 27 patients (21 men, median age 46 years) were analyzed retrospectively. All patients underwent blood tests, echocardiography, right heart catheterization, and computed tomography (CT). Spleen size was measured via CT volumetry; the splenic volume (median: 190 mL) correlated with right arterial pressure (r = 0.431, p = 0.025) and pulmonary capillary wedge pressure (r = 0.384, p = 0.048). On multivariate linear regression analysis, the heart rate (β = −0.452, p = 0.003), pump power (β = −0.325, p = 0.023), and splenic volume (β = 0.299, p = 0.038) were independent determinants of PI. The splenic volume was associated with PI, reflecting the cardiac preload in advanced HF patients with LVADs. Thus, spleen measurement using CT may help estimate the systemic volume status and understand the hemodynamic conditions in LVAD patients.

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  38. Associations between hemodynamic parameters at rest and exercise capacity in patients with implantable left ventricular assist devices.

    Kondo T, Okumura T, Oishi H, Arao Y, Kato H, Yamaguchi S, Kuwayama T, Haga T, Yokoi T, Hiraiwa H, Fukaya K, Sawamura A, Morimoto R, Mutsuga M, Fujimoto K, Usui A, Murohara T

    The International journal of artificial organs   Vol. 44 ( 3 ) page: 174 - 180   2021.3

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    Background: Hemodynamic parameters at rest are known to correlate poorly with peak oxygen uptake (VO2) in heart failure. However, we hypothesized that hemodynamic parameters at rest could predict exercise capacity in patients with left ventricular assist device (LVAD), because LVAD pump rotational speed does not respond during exercise. Therefore, we investigated the relationships between hemodynamic parameters at rest (measured with right heart catheterization) and exercise capacity (measured with cardiopulmonary exercise testing) in patients with implantable LVAD. Methods: We performed a retrospective medical record review of patients who received implantable LVAD at our institution from November 2013 to December 2017. Results: A total of 20 patients were enrolled in this study (15 males; mean age, 45.8 years; median duration of LVAD support, 356 days). The mean peak VO2 and cardiac index (CI) were 13.5 mL/kg/min and 2.6 L/min/m2, respectively. CI and hemoglobin level were significantly associated with peak VO2 (CI: r = 0.632, p = 0.003; hemoglobin: r = 0.520, p = 0.019). In addition, pulmonary capillary wedge pressure, right atrial pressure, and right ventricular stroke work index were also significantly associated with peak VO2. In multiple linear regression analysis, CI and hemoglobin level remained independent predictors of peak VO2 (CI: β = 0.559, p = 0.006; hemoglobin: β = 0.414, p = 0.049). Conclusions: CI at rest and hemoglobin level are associated with poor exercise capacity in patients with LVAD.

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  39. Impact of predictive value of Fibrosis-4 index in patients hospitalized for acute heart failure.

    Shibata N, Kondo T, Kazama S, Kimura Y, Oishi H, Arao Y, Kato H, Yamaguchi S, Kuwayama T, Hiraiwa H, Morimoto R, Okumura T, Sumi T, Sawamura A, Shimizu K, Murohara T

    International journal of cardiology   Vol. 324   page: 90 - 95   2021.2

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    Background: Abnormalities in liver function tests commonly occur in patients with acute heart failure (AHF). The Fibrosis-4 (FIB4) index, a non-invasive and easily calculated marker, has been used for hepatic diseases and reflects adverse prognosis. It is not clearly established whether the FIB4 index at admission can predict adverse outcomes in patients with AHF. Methods and results: From a multicenter AHF registry, we retrospectively evaluated 1162 consecutive patients admitted due to AHF (median age 78 [69–85] years and 702 patients [60.4%] were male). The FIB4 index at admission was calculated as: age (yrs) × aspartate aminotransferase [U/L]/(platelets count [103/μL] × √alanine aminotransferase [U/L]. The median value of the FIB4 index at admission was 2.79. All-cause mortality and rehospitalization due to HF at 12 months were investigated as a composite endpoint and occurred in 142 (12.2%) patients and 232 (20%) patients, respectively. Kaplan-Meyer analysis shows a significant increase in the composite endpoint from the first to fourth quartile group of the FIB4 index values (log-rank, p < 0.001). Multivariate Cox regression model revealed the FIB4 index was an independent risk predictor for composite endpoint in patients with AHF (3 months: HR ratio 1.013 [95% Confidence interval (CI):1.001–1.025]; p = 0.03, 12 months: HR 1.015 [95% CI:1.005–1.025]; p = 0.003, respectively). However, neither aspartate aminotransferase, alanine aminotransferase, nor platelet count was found to be a significant predictor. Conclusions: Hepatic dysfunction evaluated with the FIB4 index at admission is a predictor of the composite endpoint of all-cause mortality and rehospitalization in AHF patients.

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  40. Efficacy of favipiravir for an end stage renal disease patient on maintenance hemodialysis infected with novel coronavirus disease 2019.

    Koshi E, Saito S, Okazaki M, Toyama Y, Ishimoto T, Kosugi T, Hiraiwa H, Jingushi N, Yamamoto T, Ozaki M, Goto Y, Numaguchi A, Miyagawa Y, Kato I, Tetsuka N, Yagi T, Maruyama S

    CEN case reports   Vol. 10 ( 1 ) page: 126 - 131   2021.2

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    BACKGROUND: Novel coronavirus disease 2019 (COVID-19) refers to infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen, and has spread to pandemic levels since its inception in December 2019. While several risk factors for severe presentation have been identified, the clinical course for end-stage renal disease (ESRD) patients on maintenance hemodialysis with COVID-19 has been unclear. Previous studies have revealed that some antiviral agents may be effective against COVID-19 in the general population, but the pharmacokinetics and pharmacodynamics of these agents in ESRD patients remain under investigation. Favipiravir, an antiviral agent developed for treatment of influenza, is one candidate treatment for COVID-19, but suitable dosages for patients with renal insufficiency are unknown. Here we provide a first report on the efficacy of favipiravir in a patient with ESRD undergoing hemodialysis. CASE PRESENTATION: The case involved a 52-year-old woman with COVID-19 who had been undergoing maintenance hemodialysis three times a week for 3 years due to diabetic nephropathy. She had initially been treated with lopinavir/ritonavir and ciclesonide for 5 days, but developed severe pneumonia requiring invasive positive-pressure ventilation. Those antiviral agents were subsequently switched to favipiravir. She recovered gradually, and after 2 weeks was extubated once the viral load of SARS-CoV-2 fell below the limit of detection. Although concentrations of several biliary enzymes were elevated, no major adverse events were observed. CONCLUSION: Favipiravir may be an effective option for the treatment of COVID-19-infected patients with ESRD.

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  41. Predictors of residual mitral regurgitation after left ventricular assist device implantation.

    Kimura Y, Okumura T, Kazama S, Shibata N, Oishi H, Arao Y, Kuwayama T, Kato H, Yamaguchi S, Hiraiwa H, Kondo T, Morimoto R, Mutsuga M, Fujimoto K, Usui A, Murohara T

    The International journal of artificial organs   Vol. 44 ( 2 ) page: 101 - 109   2021.2

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    Patients with advanced heart failure often have functional mitral regurgitation. Left ventricular assist device implantation improves functional mitral regurgitation through left ventricular unloading. However, residual mitral regurgitation after left ventricular assist device implantation leads to adverse outcomes, and whether patients need concomitant mitral valve surgery is not fully elucidated. Therefore, this study aimed to elucidate the predictors of residual mitral regurgitation and to describe the temporal changes in residual mitral regurgitation. We retrospectively enrolled 15 patients with implantable continuous-flow left ventricular assist device, who had significant mitral regurgitation on echocardiography before left ventricular assist device implantation. Three patients had residual mitral regurgitation (mitral regurgitation color jet area/left atrial area >0.2) 1 month after left ventricular assist device implantation. We investigated factors associated with residual mitral regurgitation and compared patients with or without residual mitral regurgitation. On univariate analysis, mitral valve tethering area and mitral regurgitation vena contracta before left ventricular assist device implantation were significantly associated with residual mitral regurgitation (odds ratio, 1.03; p = 0.036 and odds ratio, 10.45; p = 0.0087). One month after left ventricular assist device implantation, the mean pulmonary capillary wedge pressure and pulmonary artery pressure were higher in patients with residual mitral regurgitation (pulmonary capillary wedge pressure: 11.3 ± 3.5 vs 6.4 ± 3.4 mmHg, p = 0.029 and pulmonary artery pressure: 21.3 ± 4.0 vs 15.9 ± 3.3 mmHg, p = 0.023). However, the mitral regurgitation grading and hemodynamics were not significantly different 6 months after left ventricular assist device implantation. The hospitalization-free survival was not significantly different between the two groups. Mitral valve tethering area and mitral regurgitation vena contracta were predictors of residual mitral regurgitation. Residual mitral regurgitation improved until 6 months after left ventricular assist device implantation and might not affect the prognosis.

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  42. A case of reexpansion pulmonary edema and acute pulmonary thromboembolism associated with diffuse large B-cell lymphoma treated with venovenous extracorporeal membrane oxygenation

    Kazama S.

    Journal of Cardiology Cases   Vol. 23 ( 1 ) page: 53 - 56   2021.1

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  43. Aortic insufficiency associated with Impella that required surgical intervention upon implantation of the durable left ventricular assist device.

    Oishi H, Kondo T, Fujimoto K, Mutsuga M, Morimoto R, Hirano KI, Sawamura A, Kazama S, Kimura Y, Shibata N, Kato H, Arao Y, Kuwayama T, Yamaguchi S, Hiraiwa H, Okumura T, Usui A, Murohara T

    Journal of artificial organs : the official journal of the Japanese Society for Artificial Organs   Vol. 23 ( 4 ) page: 378 - 382   2020.12

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    The Impella is an axial-flow percutaneous ventricular assist device for cardiogenic shock. In this report, we describe two patients who developed aortic insufficiency (AI) associated with Impella and required surgical intervention upon implantation of the durable left ventricular assist device (LVAD). Both patients presented with cardiogenic shock and underwent insertion of Impella 5.0 as a bridge to decision. The cardiac function in these patients did not improve and obtaining approval for heart transplantation required time. They were managed with Impella for 91 and 98 days, respectively. In both cases, moderate AI that was not present before Impella insertion was observed when the Impella was removed. Therefore, we performed aortic valve closure to control the AI during durable LVAD implantation. In patients with durable LVAD implantation, AI may occur and progress after the operation in several cases. Aortic valve surgery is often performed to prevent deterioration of AI, especially in patients with AI before the surgery. Hence, AI is an important complication following Impella device implantation as a bridge to decision. Careful observation of AI is essential when the Impella is removed as the evaluation of AI by echocardiogram during Impella management is cumbersome because of device-generated artifacts.

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  44. Relative bradycardia as a clinical feature in patients with coronavirus disease 2019 (COVID-19): A report of two cases

    Hiraiwa H.

    Journal of Cardiology Cases   Vol. 22 ( 6 ) page: 260 - 264   2020.12

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    DOI: 10.1016/j.jccase.2020.07.015

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  45. Efficacy of right ventricular dysfunction estimated by pulmonary artery pulsatility index in stable phased dilated cardiomyopathy

    Kuwayama T., Morimoto R., Oishi H., Kato H., Kimura Y., Kazama S., Shibata N., Arao Y., Yamaguchi S., Hiraiwa H., Kondo T., Furusawa K., Okumura T., Murohara T.

    EUROPEAN HEART JOURNAL   Vol. 41   page: 902 - 902   2020.11

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  46. Associations between spleen volume and exercise capacity in advanced heart failure patients with left ventricular assist device

    Hiraiwa H., Okumura T., Sawamura A., Kazama S., Kimura Y., Shibata N., Arao Y., Oishi H., Kato H., Kuwayama T., Yamaguchi S., Kondo T., Furusawa K., Morimoto R., Murohara T.

    EUROPEAN HEART JOURNAL   Vol. 41   page: 1094 - 1094   2020.11

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  47. The prognostic impact of right ventricular dysfunction in patients with septic cardiomyopathy

    Hiraiwa H., Kasugai D., Okumura T., Kazama S., Kimura Y., Shibata N., Arao Y., Oishi H., Kato H., Kuwayama T., Yamaguchi S., Kondo T., Furusawa K., Morimoto R., Murohara T.

    EUROPEAN HEART JOURNAL   Vol. 41   page: 1836 - 1836   2020.11

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  48. The efficacy of methotrexate for intolerance to prednisolone therapy in cardiac sarcoidosis

    Morimoto R., Kuwayama T., Ooishi H., Kazama S., Kimura Y., Shibata N., Hiraiwa H., Kondo T., Okumura T., Unno K., Murohara T.

    EUROPEAN HEART JOURNAL   Vol. 41   page: 2131 - 2131   2020.11

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  49. Differential Diagnosis of Mechanisms of Exercise-Induced Abnormal Blood Pressure Response in Hypertrophic Cardiomyopathy Without Left Ventricular Outflow Tract Obstruction

    Okumura Takahiro, Kano Naoaki, Sawamura Akinori, Kondo Toru, Hiraiwa Hiroaki, Morimoto Ryota, Murohara Toyoaki

    CIRCULATION-HEART FAILURE   Vol. 13 ( 10 ) page: e007164 - 551   2020.10

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  50. Impella 5.0 for Cardiogenic Shock After Thrombectomy in a Patient With Intraventricular Thrombosis

    Kimura Yuki, Kondo Toru, Mutsuga Masato, Morimoto Ryota, Kazama Shingo, Shibata Naoki, Oishi Hideo, Arao Yoshihito, Kuwayama Tasuku, Kato Hiroo, Yamaguchi Shogo, Hiraiwa Hiroaki, Okumura Takahiro, Fujimoto Kazuro, Usui Akihiko, Murohara Toyoaki

    CANADIAN JOURNAL OF CARDIOLOGY   Vol. 36 ( 10 ) page: 1690.e13 - 1690.e15   2020.10

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    A 43-year-old man was admitted to a referring hospital for cardiogenic shock caused by dilated cardiomyopathy. Intra-aortic balloon pump and percutaneous venoarterial extracorporeal membrane oxygenation (VA-ECMO) were started initially; however, a thrombus was detected in the left ventricle. After transfer to our institution, we performed thrombectomy through minithoracotomy. Subsequently, an Impella 5.0 device was inserted via the left subclavian artery. His cardiac function gradually improved, and both VA-ECMO and the Impella 5.0 could be weaned off. He was discharged without any thromboembolic event. Impella insertion with thrombectomy was possible, minimally invasive, and effective for a patient with intraventricular thrombosis associated with VA-ECMO.

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  51. Prognostic Value of Delirium in Patients With Acute Heart Failure in the Intensive Care Unit.

    Iwata E, Kondo T, Kato T, Okumura T, Nishiyama I, Kazama S, Ishihara T, Kondo S, Hiraiwa H, Tsuda T, Ito M, Aoyama M, Tanimura D, Awaji Y, Unno K, Murohara T

    The Canadian journal of cardiology   Vol. 36 ( 10 ) page: 1649 - 1657   2020.10

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    Background: Delirium is a common adverse event observed in patients admitted to the intensive care unit (ICU). However, the prognostic value of delirium and its determinants have not been thoroughly investigated in patients with acute heart failure (AHF). Methods: We investigated 408 consecutive patients with AHF admitted to the ICU. Delirium was diagnosed by means of the Confusion Assessment Method for ICU tool and evaluated every 8 hours during the patients’ ICU stays. Results: Delirium occurred in 109 patients (26.7%), and the in-hospital mortality rate was significantly higher in patients with delirium (13.8% vs 2.3%; P < 0.001). Multivariate logistic regression analysis showed that delirium independently predicted in-hospital mortality (odds ratio [OR] 4.33, confidence interval [CI] 1.62-11.52; P = 0.003). Kaplan-Meier analysis showed that the 12-month mortality rate was significantly higher in patients with delirium compared with those without (log-rank test: P < 0.001), and Cox proportional hazards analysis showed that delirium remained an independent predictor of 12-month mortality (hazard ratio 2.19, 95% CI 1.49-3.25; P < 0.001). The incidence of delirium correlated with severity of heart failure as assessed by means of the Get With The Guidelines–Heart Failure risk score (chi-square test: P = 0.003). Age (OR 1.05, 95% CI 1.02-1.09; P = 0.003), nursing home residential status (OR 3.32, 95% CI 1.59-6.94; P = 0.001), and dementia (OR 5.32, 95% CI 2.83-10.00; P < 0.001) were independently associated with the development of delirium. Conclusions: Development of delirium during ICU stay is associated with short- and long-term mortality and is predicted by the severity of heart failure, nursing home residential, and dementia status.

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  52. Pulmonary artery pressure may be a predictor of closed aortic valve in patients managed by venoarterial extracorporeal membrane oxygenation.

    Yamaguchi S, Sawamura A, Okumura T, Kato H, Oishi H, Arao Y, Haga T, Kuwayama T, Yokoi T, Hiraiwa H, Kondo T, Morimoto R, Murohara T

    The International journal of artificial organs   Vol. 43 ( 9 ) page: 594 - 599   2020.9

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    In the management of venoarterial extracorporeal membrane oxygenation, some patients present persistently closed aortic valve. However, little is known about the variables that contribute to persistently closed aortic valve. We investigated the factors that could predict persistently closed aortic valve at the time of venoarterial extracorporeal membrane oxygenation initiation. We investigated 17 patients who presented closed aortic valve immediately after the introduction of venoarterial extracorporeal membrane oxygenation. Patients who presented closed aortic valve 24 h after introduction of venoarterial extracorporeal membrane oxygenation were defined as the Closed-AV group (n = 8), while those whose aortic valve remained opened after 24 h were defined as the Open-AV group (n = 9). All patients were managed by concomitant use of intra-aortic balloon pumping. At baseline, there were no significant differences between mean arterial blood pressure, central venous pressure, and left ventricular ejection fraction. However, Closed-AV group had significantly lower mean pulmonary artery pressure and pulmonary artery pulse pressure compared to those of Open-AV group (mean pulmonary artery pressure: 15 ± 6 mmHg vs 25 ± 8 mmHg, p = 0.01; pulmonary artery pulse pressure: 3 ± 2 mmHg vs 8 ± 3 mmHg, p < 0.01). Logistic regression analyses revealed that the lower mean pulmonary artery pressure and pulmonary artery pulse pressure had the predictive value of closed aortic valve within 24 h after venoarterial extracorporeal membrane oxygenation initiation (mean pulmonary artery pressure: odds ratio = 0.78, 95% confidence interval = 0.58–0.95, p < 0.01; pulmonary artery pulse pressure: odds ratio = 0.18, 95% confidence interval = 0.01–0.61, p < 0.01). Lower mean pulmonary artery pressure and pulmonary artery pulse pressure values could predict persistent closed aortic valve 24 h after venoarterial extracorporeal membrane oxygenation initiation. Left ventricular preload derived from right heart function may have a major impact on aortic valve status.

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  53. Efficacy of Pulmonary Artery Pulsatility Index as a Measure of Right Ventricular Dysfunction in Stable Phase of Dilated Cardiomyopathy

    Kuwayama Tasuku, Morimoto Ryota, Oishi Hideo, Kato Hiroo, Kimura Yuki, Kazama Shingo, Shibata Naoki, Arao Yoshihito, Yamaguchi Shogo, Hiraiwa Hiroaki, Kondo Toru, Furusawa Kenji, Okumura Takahiro, Murohara Toyoaki

    Circulation Journal   Vol. 84 ( 9 ) page: 1536 - 1543   2020.8

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    <p><b><i>Background:</i></b>Right ventricular dysfunction (RVD) in the setting of left ventricular (LV) myocardial damage is a major cause of morbidity and mortality, and the pulmonary artery pulsatility index (PAPi) is a novel hemodynamic index shown to predict RVD in advanced heart failure. However, it is unknown whether PAPi can predict the long-term prognosis of dilated cardiomyopathy (DCM) even in the mild to moderate phase. This study aimed to assess the ability of PAPi to stratify DCM patients without severe symptoms.</p><p><b><i>Methods and Results:</i></b>Between April 2000 and March 2018, a total of 162 DCM patients with stable symptoms were evaluated, including PAPi, and followed up for a median of 4.91 years. The mean age was 50.9±12.6 years and the mean LV ejection fraction (EF) was 30.5±8.3%. When divided into 2 groups based on median value of PAPi (low, L-PAPi [<3.06] and high, H-PAPi [≥3.06]), even though there were no differences in B-type natriuretic peptide or pulmonary vascular resistance, the probability of cardiac event survival was significantly higher in the L-PAP than in the H-PAP group by Kaplan-Meier analysis (P=0.018). Furthermore, Cox’s proportional hazard regression analysis revealed that PAPi was an independent predictor of cardiac events (hazard ratio: 0.782, P=0.010).</p><p><b><i>Conclusions:</i></b>Even in patients identified with DCM in the mild to moderate phase, PAPi may help stratify DCM and predict cardiac events.</p>

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  54. Fulminant myocarditis with myositis of ocular and respiratory muscles

    Hiraiwa Hiroaki, Furusawa Kenji, Kazama Shingo, Kimura Yuki, Shibata Naoki, Arao Yoshihito, Oishi Hideo, Kato Hiroo, Kuwayama Tasuku, Yamaguchi Shogo, Kondo Toru, Sawamura Akinori, Morimoto Ryota, Okumura Takahiro, Murohara Toyoaki

    NAGOYA JOURNAL OF MEDICAL SCIENCE   Vol. 82 ( 3 ) page: 585 - 593   2020.8

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    A 46-year-old Japanese woman visited a nearby hospital because of diplopia after flu-like symptoms. One month later, she presented with blepharoptosis and external ophthalmoplegia. Laboratory tests showed a high creatine kinase concentration (3146 U/L). She underwent intravenous immunoglobulin therapy; however, her symptoms did not improve, prompting transfer to our institute. On admission, transthoracic echocardiography revealed 30% of left ventricular ejection fraction and edema of the left ventricular wall. Coronary angiography showed no significant coronary stenosis. An endomyocardial biopsy resulted in a diagnosis of acute myocarditis. On the following day, she needed a temporary pacemaker because she had complete atrioventricular block and intra-aortic balloon pump because of cardiogenic shock. Intravenous immunoglobulin therapy was again administered and her cardiac function gradually recovered. She was successfully weaned off her temporary pacemaker and intra-aortic balloon pump on Day 5 after improvement in her complete atrioventricular block. Steroid therapy administered from Day 9 was effective in reducing her creatine kinase concentrations. However, contrast-enhanced magnetic resonance imaging revealed inflammation of the scalene, semispinalis cervicis, sternocleidomastoid, and intercostal muscles. On Day 25, her cardiac function had recovered to a left ventricular ejection fraction of 59%. Finally, she was successfully discharged on Day 45 after undergoing rehabilitation.

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  55. Usefulness of Plasma Branched-Chain Amino Acid Analysis in Predicting Outcomes of Patients with Nonischemic Dilated Cardiomyopathy

    Kimura Yuki, Okumura Takahiro, Kazama Shingo, Shibata Naoki, Oishi Hideo, Arao Yoshihito, Kuwayama Tasuku, Kato Hiroo, Yamaguchi Shogo, Hiraiwa Hiroaki, Kondo Toru, Morimoto Ryota, Murohara Toyoaki

    International Heart Journal   Vol. 61 ( 4 ) page: 739 - 747   2020.7

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    <p>The metabolism of branched-chain amino acids (BCAAs) is reported to change in heart failure (HF) and correlate with cardiac function. However, the effect of BCAAs on HF remains controversial. We investigate the prognostic value of the plasma BCAA level in nonischemic dilated cardiomyopathy (NIDCM).</p><p>This study enrolled 39 NIDCM patients, who underwent plasma amino acid (AA) analysis. The ratio of BCAAs to total AAs was calculated. All patients were divided into two groups at the median of BCAA/total AA ratio; high BCAA/total AA group (≥ 0.15, <i>n</i> = 20) and low BCAA/total AA group (< 0.15, <i>n</i> = 19). A cardiac event was defined as a composite of cardiac death, hospitalization for worsening HF, and lethal arrhythmia.</p><p>The mean age was 51.1 ± 12.3 years and left ventricular ejection fraction (LVEF) was 32.7 ± 10.1%. In the low BCAA/total AA group, the body mass index and the total cholesterol level were lower than in the high BCAA/total AA group. The BCAA/total AA ratio was positively correlated with LVEF (<i>r</i> = 0.35, <i>P</i> = 0.031) and negatively correlated with brain natriuretic peptide (<i>r</i> = −0.37, <i>P</i> = 0.020). The low BCAA/total AA group had a lower cardiac event-free rate (5-year: 100% versus 73%; <i>P</i> = 0.019). In univariate analysis, angiotensin converting enzyme inhibitor or angiotensin II receptor blocker (hazard ratio: 0.045, <i>P</i> = 0.0014), hemoglobin (hazard ratio: 0.49 per 1 g/dL, <i>P</i> = 0.0022), and BCAA/total AA ratio < 0.15 (hazard ratio: not available, <i>P</i> = 0.0066) were major predictors for cardiac events.</p><p>The BCAA/total AA ratio might be a useful predictor for future cardiac events in patients with NIDCM.</p>

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  56. Spleen size improvement in advanced heart failure patients using a left ventricular assist device.

    Hiraiwa H, Okumura T, Sawamura A, Kondo T, Kazama S, Kimura Y, Shibata N, Arao Y, Oishi H, Kato H, Kuwayama T, Yamaguchi S, Furusawa K, Morimoto R, Murohara T

    Artificial organs   Vol. 44 ( 7 ) page: 700 - 708   2020.7

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    The spleen has been recognized as an important organ that holds a reserve of 20% to 30% of the total blood volume. Spleen contraction and splenic volume reduction occur in patients with hypovolemic shock. However, the change in the spleen volume and the association between spleen size and hemodynamic parameters remain unclear in patients with advanced heart failure (HF) who need left ventricular assist device (LVAD) support. This study was performed to investigate the change in spleen size and the relationship between spleen size and hemodynamic parameters before and after LVAD implantation in patients with advanced HF. We enrolled 20 patients with advanced HF on LVAD support. All patients underwent right heart catheterization and computed tomography before and after LVAD implantation. The spleen size was measured by computed tomography volumetry. We excluded patients with a mean right atrial pressure (RAP) of <5 mm Hg because of the possibility of hypovolemia and those with a cardiac index of >2.2 L/min/m2 before LVAD implantation. The splenic volume significantly increased from 160.6 ± 46.9 mL before LVAD implantation to 224.6 ± 73.5 mL after LVAD implantation (P <.001). Before LVAD implantation, there was a significant negative correlation between spleen volume and systemic vascular resistance (SVR). After LVAD implantation, however, there were significant correlations between spleen volume and the cardiac index, RAP, and pulmonary capillary wedge pressure despite the absence of a significant correlation between spleen volume and SVR. Furthermore, one patient developed reworsening HF because of LVAD failure due to pump thrombosis. In this case, the splenic volume was 212 mL before LVAD implantation and increased to 418 mL after LVAD implantation, although it decreased to 227 mL after LVAD failure. The spleen size may change depending on hemodynamics in patients with advanced HF with LVAD support, reflecting sympathetic nerve activity and the systemic volume status.

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  57. Usefulness of the plasma branched-chain amino acid/aromatic amino acid ratio for predicting future cardiac events in patients with heart failure.

    Hiraiwa H, Okumura T, Kondo T, Kato T, Kazama S, Ishihara T, Iwata E, Shimojo M, Kondo S, Aoki S, Kanzaki Y, Tanimura D, Sano H, Awaji Y, Yamada S, Murohara T

    Journal of cardiology   Vol. 75 ( 6 ) page: 689 - 696   2020.6

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    Background: Heart failure (HF) is a hypercatabolic state that promotes branched-chain amino acid (BCAA) catabolic activity in the heart and skeletal muscle and reduces protein synthesis in the liver. Consequently, plasma free aromatic amino acids (AAAs) are increased. We investigated the prognostic value of the BCAA/AAA ratio (Fischer's ratio, FR) in patients with HF. Methods: We enrolled 157 consecutive patients hospitalized for worsening HF (81 men, 76 women; mean ± SD age 75 ± 14 years). Plasma BCAA levels (i.e. total leucine, isoleucine, valine) and AAA levels (i.e. total tyrosine, phenylalanine) were measured at a time when the patients were stabilized (at discharge). FR was calculated as the combined plasma BCAA levels divided by the AAA level. Cardiac events were defined as a composite of cardiac death and hospitalization for worsening HF. Results: The patients were divided into two groups based on the median FR (high-FR group: FR ≥ 3.1, n = 78; low-FR group: FR < 3.1, n = 79). Compared with the high-FR group, low-FR patients were older, had more prior hospitalizations for HF, lower albumin and cholinesterase levels, and lower geriatric nutritional risk index (GNRI). Altogether, 46 cardiac events occurred during the follow-up period (221 ± 135 days), including 14 cardiac deaths and 32 hospitalizations for worsening HF. In a Kaplan–Meier survival analysis, the low-FR group had more cardiac events than the high-FR group (log-rank, p < 0.001). The best cut-off value of FR was determined as 2.9 in the receiver operating characteristic curve for cardiac events. A multivariate Cox proportional hazards regression analysis showed that being in the low-FR group was an independent determinant of cardiac events from parameters of liver function tests and GNRI. Conclusions: FR might be useful for predicting future cardiac events in patients with HF, reflecting nutritional status which cannot be assessed by liver function tests and GNRI.

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  58. Pathological changes of the myocardium in reworsening of anthracycline-induced cardiomyopathy after explant of a left ventricular assist device

    Hiraiwa Hiroaki, Okumura Takahiro, Shimizu Shinya, Arao Yoshihito, Oishi Hideo, Kato Hiroo, Kuwayama Tasuku, Yamaguchi Shogo, Haga Tomoaki, Yokoi Tsuyoshi, Kondo Toru, Sugiura Yuki, Kano Naoaki, Watanabe Naoki, Fukaya Kenji, Furusawa Kenji, Sawamura Akinori, Morimoto Ryota, Fujimoto Kazuro, Mutsuga Masato, Usui Akihiko, Murohara Toyoaki

    NAGOYA JOURNAL OF MEDICAL SCIENCE   Vol. 82 ( 1 ) page: 129 - 134   2020.2

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    We herein report the long-term changes in cardiac function and pathological findings after successful explantation of a left ventricular assist device in a 42-year-old patient with anthracycline-induced cardiomyopathy with reworsening heart failure. Endomyocardial biopsy samples revealed that the cardiomyocyte diameter decreased and collagen volume fraction increased just after left ventricular assist device explantation. The collagen volume fraction decreased after 6 months, despite preserved systolic function. At 5 years after left ventricular assist device explantation, the systolic function markedly decreased and cardiomyocyte diameter increased. Pathological changes of the myocardium may enable the identification of cardiac dysfunction prior to echocardiographic changes in patients with reworsening heart failure after left ventricular assist device explantation.

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  59. Giant cell myocarditis with central diabetes insipidus: A case report

    Yamaguchi S.

    Journal of Cardiology Cases   Vol. 21 ( 1 ) page: 8 - 11   2020.1

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  60. Two cases of dilated cardiomyopathy with blood pressure-limited tolerability of cardioprotective agents improved by ivabradine

    Okumura T.

    Journal of Cardiology Cases     2020

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  61. Fulminant Myocarditis with Myositis of Ocular and Respiratory Muscles: A Case Report Reviewed

    平岩 宏章

    Nagoya Journal of Medical Science   Vol. -   2020

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  62. Potential prognostic implications of myocardial thallium-201 and iodine-123-beta-methylpentadecanoic acid dual scintigraphy in patients with Anderson-Fabry disease.

    Haga T, Okumura T, Isobe S, Somura F, Kano N, Kuwayama T, Yokoi T, Hiraiwa H, Kondo T, Sawamura A, Morimoto R, Yamamoto H, Tsuboi K, Murohara T

    Annals of nuclear medicine   Vol. 33 ( 12 ) page: 930 - 936   2019.12

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    Objectives: Information on the relationship between myocardial damage assessed by myocardial scintigraphy and prognosis in patients with Anderson–Fabry disease (AFD) is lacking. We therefore aimed to investigate the prognostic impacts of myocardial thallium-201 (201Tl) and iodine-123 beta-methyl 15-para-iodophenyl 3(R, S)-methylpentadecanoic acid (123I-BMIPP) dual scintigraphy in patients with AFD. Methods: Eighteen consecutive patients with AFD underwent resting myocardial 201Tl/123I-BMIPP dual scintigraphy. Total defect scores (TDS) on both images were calculated visually according to the 17-segment model using a 5-point scoring system. The mismatch score (MS) was calculated as ‘TDS on 123I-BMIPP—TDS on 201Tl’. Results: Six major adverse cardiac events (MACEs) were recorded during a mean follow-up of 6.7 ± 4.2 years (three heart failure requiring hospitalization and three cardiac deaths). Left ventricular mass index, left atrial diameter, brain natriuretic peptide, TDS on 123I-BMIPP, and MS were all significantly greater in patients with MACEs compared with those without. Kaplan–Meier analysis indicated that high TDS on 123I-BMIPP and high MS were associated with poor event-free survival. Conclusion: TDS on 123I-BMIPP was a better prognostic determinant in patients with AFD than TDS on 201Tl. Myocardial 201Tl/123I-BMIPP dual scintigraphy may thus be a useful noninvasive modality for evaluating prognosis in patients with AFD.

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  63. Prognostic impact of mitral L-wave in patients with hypertrophic cardiomyopathy without risk factors for sudden cardiac death.

    Sugiura Y, Morimoto R, Aoki S, Yamaguchi S, Haga T, Kuwayama T, Yokoi T, Hiraiwa H, Kondo T, Watanabe N, Kano N, Fukaya K, Sawamura A, Okumura T, Murohara T

    Heart and vessels   Vol. 34 ( 12 ) page: 2002 - 2010   2019.12

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    Hypertrophic cardiomyopathy (HCM) with severe diastolic dysfunction is a major cause of heart failure and sudden cardiac death (SCD) associated with lethal arrhythmia. Although various risk factors for cardiac events have been reported in HCM patients, previous studies have reported that some HCM patients exhibit either no risk or a low risk of SCD experienced cardiac events. The mid-diastolic transmitral flow velocity curve (mitral L-wave) is an echocardiographic index of left ventricular compliance, and it has been reported as one of the parameters of advanced diastolic dysfunction assessed noninvasively. However, little is known about the association between the mitral L-wave and long-term clinical outcomes in HCM patients without SCD risk factors. Between July 2005 and February 2016, 112 patients were diagnosed with HCM and 96 patients without risk factors were enrolled. After excluding 3 patients whom we could not detect L-wave more than once, 93 patients (mean age 57.7 ± 13.1 years, 33 females) were divided into the following two groups, according to the presence or absence of the mitral L-wave: Group L (+) (with the mitral L-wave) and Group L (−) (without the mitral L-wave). The correlations between the mitral L-wave and rates of cardiac events were investigated. The mitral L-wave was present in 14 (15.1%) patients [Group L]. During the follow-up period [4.7 (2.9–7.5) years], patients experienced 7 cardiac events. Kaplan–Meier survival analysis showed that the event-free rate was significantly lower in Group L (+) than in Group L (−) (log-rank P = 0.002). Additionally, in multivariate analysis, L-wave positivity was identified as independent predictors of cardiac events. Existence of the mitral L-wave can predict cardiac events, even in HCM patients without SCD risk factors.

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  64. Circulating human epididymis protein 4 is a novel prognostic predictor in ambulatory patients with non-ischemic dilated cardiomyopathy

    Okumura T., Oishi H., Kondo T., Arao Y., Kato H., Haga T., Yamaguchi S., Kuwayama T., Yokoi T., Hiraiwa H., Sawamura A., Morimoto R., Murohara T.

    EUROPEAN HEART JOURNAL   Vol. 40   page: 4051 - 4051   2019.10

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  65. Neuromuscular electrical stimulation is feasible in patients with acute heart failure.

    Kondo T, Yamada S, Tanimura D, Kazama S, Ishihara T, Shimojo M, Iwata E, Kondo S, Hiraiwa H, Kato T, Sano H, Awaji Y, Okumura T, Murohara T

    ESC heart failure   Vol. 6 ( 5 ) page: 975 - 982   2019.10

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    Aims: In acute heart failure (AHF), immobilization is caused because of unstable haemodynamics and dyspnoea, leading to protein wasting. Neuromuscular electrical stimulation (NMES) has been reported to preserve muscle mass and improve functional outcomes in chronic disease. NMES may be effective against protein wasting frequently manifested in patients with AHF; however, whether NMES can be implemented safely without any adverse effect on haemodynamics has remained unknown. This study aimed to examine the feasibility of NMES in patients with AHF. Methods and results: Patients with AHF were randomly assigned to the NMES or control group. The intensity of the NMES group was set at 10–20% maximal voluntary contraction level, whereas the control group was limited at a visible or palpable level of muscle contraction. The sessions were performed 5 days per week since the day after admission. Before the study implementation, we set the feasibility criteria with following items: (i) change in systolic blood pressure (BP) > ±20 mmHg during the first session; (ii) increase in heart rate (HR) > +20 b.p.m. during the first session; (iii) development of sustained ventricular arrhythmia, atrial fibrillation (AF), and paroxysmal supraventricular tachycardia during all sessions; (iv) incidence of new-onset AF during the hospitalization period < 40%; and (v) completion of the planned sessions by >70% of patients. The criteria of feasibility were set as follows; the percentage to fill one of (i)–(iii) was <20% of the total subjects, and both (iv) and (v) were satisfied. A total of 73 patients (median age 72 years, 51 men) who completed the first session were analysed (NMES group, n = 34; control group, n = 39). Systolic BP and HR variations were not significantly different between two groups (systolic BP, P = 0.958; HR, P = 0.665). Changes in BP > ±20 mmHg or HR > +20 b.p.m. were observed in three cases in the NMES group (8.8%) and five in the control group (12.8%). New-onset arrhythmia was not observed during all sessions in both groups. During hospitalization, one patient newly developed AF in the NMES group (2.9%), and one developed AF (2.6%) and two lethal ventricular arrhythmia in the control group. Thirty-one patients in the NMES group (91%) and 33 patients in the control group (84%) completed the planned sessions during hospitalization. This study fulfilled the preset feasibility criteria. Conclusions: NMES is feasible in patients with AHF from immediately after admission.

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  66. Early blood pressure reduction by intravenous vasodilators associates with acute kidney injury in patients with hypertensive acute decompensated heart failure

    Arao Y., Sawamura A., Nakatochi M., Oishi H., Kato H., Yamaguchi S., Haga T., Kuwayama T., Yokoi T., Hiraiwa H., Kondo T., Morimoto R., Okumura T., Murohara T.

    EUROPEAN HEART JOURNAL   Vol. 40   page: 884 - 884   2019.10

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  67. Pulmonary artery pressure could predict closed aortic valve in patients managed by veno-arterial extracorporeal membrane oxygenation

    Yamaguchi S., Sawamura A., Arao Y., Ooishi H., Kato H., Kuwayama T., Haga T., Hiraiwa H., Yokoi T., Kondo T., Morimoto R., Okumura T., Murohara T.

    EUROPEAN HEART JOURNAL   Vol. 40   page: 953 - 953   2019.10

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  68. The increased serum level of troponin T after immunosuppression therapy reflects sustained myocardial FDG accumulation in cardiac sarcoidosis

    Morimoto R., Unno K., Ooishi H., Arao Y., Kato H., Yokoi T., Yamaguchi S., Haga T., Kuwayama T., Hiraiwa H., Kondo T., Sawamura A., Okumura T., Murohara T.

    EUROPEAN HEART JOURNAL   Vol. 40   page: 648 - 648   2019.10

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  69. Splenic volume changes as a hemodynamic parameter in advanced heart failure with left ventricular assist device

    Hiraiwa H., Okumura T., Sawamura A., Kondo T., Arao Y., Oishi H., Kato H., Kuwayama T., Yamaguchi S., Haga T., Yokoi T., Fukaya K., Furusawa K., Morimoto R., Murohara T.

    EUROPEAN HEART JOURNAL   Vol. 40   page: 3303 - 3303   2019.10

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  70. Early Blood Pressure Reduction by Intravenous Vasodilators Is Associated With Acute Kidney Injury in Patients With Hypertensive Acute Decompensated Heart

    Arao Yoshihito, Sawamura Akinori, Nakatochi Masahiro, Okumura Takahiro, Kato Hiroo, Oishi Hideo, Yamaguchi Shogo, Haga Tomoaki, Kuwayama Tasuku, Yokoi Tsuyoshi, Hiraiwa Hiroaki, Kondo Toru, Morimoto Ryota, Murohara Toyoaki

    Circulation Journal   Vol. 83 ( 9 ) page: 1883 - 1890   2019.8

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    <p><b><i>Background:</i></b>Intravenous vasodilators are commonly used in patients with hypertensive acute decompensated heart failure (ADHF), but little is known about their optimal use in blood pressure (BP) management to avoid acute kidney injury (AKI). The purpose of this study was to investigate the association between systolic BP (SBP) changes and the incidence of AKI in patients with hypertensive ADHF.</p><p><b><i>Methods and Results:</i></b>Post-hoc analysis was performed on a prospectively enrolled cohort. We investigated 245 patients with ADHF and SBP >140 mmHg on arrival (mean age, 76 years; 40% female). We defined “SBP-fall” as the maximum percent reduction in SBP 6 h after intravenous treatment. AKI was defined as serum creatinine (SCr) ≥0.3 mg/dL, or urine output <0.5 mL/kg/h (n=66) at 48 h. Mean SBP and SCr levels on arrival were 180 mmHg and 1.21 mg/dL, respectively. Patients with AKI had significantly larger SBP-fall than the others (36.7±15.3% vs. 27.2±15.3%, P<0.0001). Logistic regression analysis showed an odds ratio per 10% SBP-fall for AKI of 1.49 (95% confidence interval 1.29–1.90, P=0.001). SBP-fall was significantly associated with the number of concomitant used intravenous vasodilators (P=0.001). The administration of carperitide was also independently associated with increased incidence of AKI.</p><p><b><i>Conclusions:</i></b>Larger SBP-fall from excessive vasodilator use is associated with increased incidence of AKI in patients with hypertensive ADHF.</p>

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  71. Left Ventricular Relaxation Half-Time as a Predictor of Cardiac Events in Idiopathic Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy With Left Ventricular Systolic and/or Diastolic Dysfunction.

    Yokoi T, Morimoto R, Oishi H, Kato H, Arao Y, Yamaguchi S, Kuwayama T, Haga T, Hiraiwa H, Kondo T, Furusawa K, Fukaya K, Sawamura A, Okumura T, Hirashiki A, Murohara T

    The American journal of cardiology   Vol. 124 ( 3 ) page: 435 - 441   2019.8

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    Purpose: Diastolic dysfunction preceding systolic dysfunction is considered an important interaction in cardiomyopathy with poor prognosis. The aim of this study was to compare left ventricular (LV) isovolumic relaxation with the other parameters as a potential prognostic marker for patients with idiopathic dilated cardiomyopathy (IDC) and hypertrophic cardiomyopathy (HC). Methods: A total of 145 patients with IDC and 116 with HC were evaluated for hemodynamic parameters; LV pressure was directly measured by a micromanometer catheter, and relaxation half-time (T1/2) was used to determine LV isovolumic relaxation. The median follow-up period was 4.7 years. Results: The mean ages of the patients with IDC and HC were 52.0 ± 12.0 and 57.1 ± 12.4 years, respectively. Each patient group was further divided into 2 groups based on the median value of T1/2: (1) <41.0 ms (D-L group) and ≥41.0 ms (D-H group) (2) <38.5 ms (H-L group) and ≥38.5 ms (H-H group). Kaplan-Meier analysis showed a significantly higher probability of cardiac events in the D-H group than in the D-L group (p = 0.001) and in the H-H group than in the H-L group (p = 0.028). Further, Cox proportional hazard regression analysis revealed that T1/2 was an independent predictor of cardiac events for patients with IDC (hazard ratio 1.109; p = 0.007) and HC (hazard ratio 1.062; p = 0.041). In conclusion, regardless of the type of cardiomyopathy, T1/2 as a measure of LV isovolumic relaxation function was found to be associated with the occurrence of cardiac events.

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  72. A survival case of a young adult patient with ST-elevated myocardial infarction with high levels of lipoprotein(a)

    Hiraiwa H.

    Journal of Cardiology Cases   Vol. 19 ( 6 ) page: 207 - 210   2019.6

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  73. Hemodynamics of cardiac tamponade during extracorporeal membrane oxygenation support in a patient with fulminant myocarditis

    Kondo T.

    Journal of Cardiology Cases   Vol. 19 ( 1 ) page: 22 - 24   2019.1

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  74. Author's reply.

    Hiraiwa H, Okumura T, Sawamura A, Murohara T

    Journal of cardiology   Vol. 72 ( 3 ) page: 266 - 266   2018.9

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  75. Haemodynamic and electrical safety of neuromuscular electrical stimulation in acute decompensated heart failure

    Kondo T., Yamada S., Okumura T., Kazama S., Ishihara T., Shimojo M., Iwata E., Kondo S., Hiraiwa H., Tanimura D., Kato T., Awaji Y., Murohara T.

    EUROPEAN HEART JOURNAL   Vol. 39   page: 908 - 908   2018.8

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  76. Promising method for management of venoarterial extracorporeal membrane oxygenation: A case of severe heart failure successfully stabilized by “high-flow/vasodilation method”

    Kondo T.

    Journal of Cardiology Cases   Vol. 18 ( 2 ) page: 81 - 84   2018.8

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    DOI: 10.1016/j.jccase.2018.05.002

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  77. Corrigendum to "The Selvester QRS score as a predictor of cardiac events in nonischemic dilated cardiomyopathy" [J. Cardiol. 71 (2018) 284-290].

    Hiraiwa H, Okumura T, Sawamura A, Sugiura Y, Kondo T, Watanabe N, Aoki S, Ichii T, Kitagawa K, Kano N, Fukaya K, Furusawa K, Morimoto R, Takeshita K, Bando YK, Murohara T

    Journal of cardiology   Vol. 72 ( 2 ) page: 178 - 178   2018.8

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    There is an error in the section of methods of statistical analysis. Correctly, the covariates with p < 0.01 in univariate analysis were retested for multivariate analysis. In addition, Table 3 is incorrect. Please see the corrected Table 3 here.

    DOI: 10.1016/j.jjcc.2018.02.001

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  78. Tau as a predictor of cardiac events in cardiomyopathy with systolic and/or diastolic dysfunction

    Yokoi T., Morimoto R., Okumura T., Yamaguchi S., Kuwayama T., Hiraiwa H., Haga T., Kondo T., Sugiura Y., Watanabe N., Kano N., Sawamura A., Murohara T.

    EUROPEAN HEART JOURNAL   Vol. 39   page: 1386 - 1387   2018.8

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  79. Late-Onset Fulminant Myocarditis With Immune Checkpoint Inhibitor Nivolumab.

    Yamaguchi S, Morimoto R, Okumura T, Yamashita Y, Haga T, Kuwayama T, Yokoi T, Hiraiwa H, Kondo T, Sugiura Y, Watanabe N, Kano N, Kohno K, Fukaya K, Sawamura A, Yokota K, Ishii H, Nakaguro M, Akiyama M, Murohara T

    The Canadian journal of cardiology   Vol. 34 ( 6 ) page: 812.e1 - 812.e3   2018.6

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    A 60-year-old man was diagnosed with melanoma. After receiving 13 infusions of nivolumab, he had fulminant myocarditis. The myocardial biopsy specimen revealed extensive lymphocytic infiltration, interstitial edema, and myocardial necrosis, with predominant CD4+, CD8+, CD20− and programmed death-1− markers. Programmed death-1 ligand 1 (PD-L1) was predominantly expressed on the surface of the damaged myocardium. Although it is reported that myocarditis induced by the human anti-programmed death-1 inhibitor nivolumab therapy rarely occurred at > 2 months use in clinical trials, this case showed that even if at a late phase, long-term use of immune checkpoint inhibitors might to lead immune-related adverse events including myocarditis.

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  80. The Selvester QRS score as a predictor of cardiac events in nonischemic dilated cardiomyopathy.

    Hiraiwa H, Okumura T, Sawamura A, Sugiura Y, Kondo T, Watanabe N, Aoki S, Ichii T, Kitagawa K, Kano N, Fukaya K, Furusawa K, Morimoto R, Takeshita K, Bando YK, Murohara T

    Journal of cardiology   Vol. 71 ( 3 ) page: 284 - 290   2018.3

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    Background: Myocardial fibrosis is associated with poor prognosis in nonischemic dilated cardiomyopathy (NIDCM) patients. The Selvester QRS score on 12-lead electrocardiogram is associated with both the amount of myocardial scar and poor prognosis in myocardial infarction patients. However, its use in NIDCM patients is limited. We investigated the prognostic value of the QRS score and its association with collagen volume fraction (CVF) in NIDCM patients. Methods: We enrolled 91 consecutive NIDCM patients (66 men, 53 ± 13 years) without permanent pacemakers or cardiac resynchronization therapy devices. The Selvester QRS score was calculated by two expert cardiologists at NIDCM diagnosis. All patients were followed up over 4.5 ± 3.2 years. Cardiac events were defined as a composite of cardiac death, hospitalization for worsening heart failure, and lethal arrhythmia. We also evaluated CVF using endomyocardial biopsy samples. Results: At baseline, the left ventricular ejection fraction was 32 ± 9%, plasma brain natriuretic peptide level was 80 [43–237] pg/mL, and mean Selvester QRS score was 4.1 points. Twenty cardiac events were observed (cardiac death, n = 1; hospitalization for worsening heart failure, n = 16; lethal arrhythmia, n = 3). Cox proportional hazard regression analysis revealed that the Selvester QRS score was an independent determinant of cardiac events (hazard ratio, 1.32; 95% confidence interval, 1.05–1.67; p = 0.02). The best cut-off value was determined as 3 points, with 85% sensitivity and 47% specificity (area under the curve, 0.688, p = 0.011). In Kaplan–Meier survival analysis, the QRS score ≥3 group had more cardiac events than the QRS score <3 group (log-rank, p = 0.007). Further, there was a significant positive correlation of Selvester QRS score with CVF (r = 0.46, p < 0.001). Conclusions: The Selvester QRS score can predict future cardiac events in NIDCM, reflecting myocardial fibrosis assessed by CVF.

    DOI: 10.1016/j.jjcc.2017.09.002

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  81. Impact of Renal Functional/Morphological Dynamics on the Calcification of Coronary and Abdominal Arteries in Patients with Chronic Kidney Disease

    Ichii Takeo, Morimoto Ryota, Okumura Takahiro, Ishii Hideki, Tatami Yosuke, Yamamoto Dai, Aoki Soichiro, Hiraiwa Hiroaki, Furusawa Kenji, Kondo Toru, Watanabe Naoki, Kano Naoaki, Fukaya Kenji, Sawamura Akinori, Suzuki Susumu, Yasuda Yoshinari, Murohara Toyoaki

    Journal of Atherosclerosis and Thrombosis   Vol. 24 ( 11 ) page: 1092 - 1104   2017.11

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    <p><i><b>Aim</b></i>: Fast-progressing vascular calcification (VC) is accompanied by renal atrophy and functional deterioration along with atherosclerosis in patients with chronic kidney disease (CKD). However, the relationship between VC progression and renal functional and/or morphological changes remains unclear.</p><p><i><b>Methods</b></i>: We included 70 asymptomatic patients with CKD without hemodialysis in our study. To identify temporal variations, the coronary artery calcification score (CACS), abdominal aortic calcification index (ACI), and renal parenchymal volume index (RPVI) were determined via spiral computed tomography scans taken during the study. We investigated significant factors related to annualized variations of CACS (<i>Δ</i>CACS/y) and ACI (<i>Δ</i>ACI/y).</p><p><i><b>Results</b></i>: During the follow-up period (4.6 years), median values of CACS [in Agatston units (AU)] and ACI increased from 40.2 to 113.3 AU (<i>p</i>=0.053) and from 13.2 to 21.7% (<i>p</i>=0.036), respectively. Multivariate analysis revealed that CACS at baseline (<i>p</i><0.001) and diabetes mellitus (DM) status (<i>p</i>=0.037) for <i>Δ</i>CACS/y and ACI at baseline (<i>p</i>=0.017) and hypertension (HT) status (<i>p</i>= 0.046) for <i>Δ</i>ACI/y were significant independent predictors. Furthermore, annualized RPVI variation was significantly related to both <i>Δ</i>CACS/y and <i>Δ</i>ACI/y (R=−0.565, <i>p</i><0.001, and R=−0.289, <i>p</i>=0.015, respectively). On the other hand, independent contributions of the estimated glomerular filtration rate (eGFR) and annualized eGFR variation to VC progression were not confirmed.</p><p><i><b>Conclusion</b></i>: The degree of VC at baseline, DM, HT, and changes in renal volume, but not eGFR, had a strong impact on VC progression in patients with CKD.</p>

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  82. Myocardial contractile reserve predicts left ventricular reverse remodeling and cardiac events in dilated cardiomyopathy.

    Morimoto R, Okumura T, Hirashiki A, Ishii H, Ichii T, Aoki S, Furusawa K, Hiraiwa H, Kondo T, Watanabe N, Kano N, Fukaya K, Sawamura A, Takeshita K, Bando YK, Murohara T

    Journal of cardiology   Vol. 70 ( 4 ) page: 303 - 309   2017.10

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    Background Catecholamine sensitivity estimated using a dobutamine stress test (DST) is recognized as a measure of the beta-adrenergic myocardial contractile reserve, which is involved with left ventricular reverse remodeling (LV-RR). We investigated whether the prognostic ability of the DST for LV-RR could predict cardiac events. Methods There was a total of 192 enrolled patients with dilated cardiomyopathy (DCM). DCM was defined as a LV ejection fraction (LV-EF) ≤45% and LV end-diastolic dimension (LVDd) ≥55 mm. One hundred patients were subjected to micromanometer-based measurement of the maximal first derivative of LV pressure (LVdP/dtmax), an index of LV contractility, at baseline and following the infusion of dobutamine (10 μg/kg/min) via a pigtail catheter. Percentage changes in LVdP/dtmax from the baseline to peak values under dobutamine stress (ΔLVdP/dtmax) were also calculated. After excluding 17 patients who received cardiac resynchronization therapy within 3 months of undergoing DST (n = 15) and who did not receive follow-up echocardiography (n = 2), 83 patients were enrolled (52.5 ± 12.3 years). Results During the follow-up period (4.7 ± 2.6 years), LV-RR was recognized in 49 of 83 patients (59.0%). A multivariate logistic regression analysis revealed that ΔLVdP/dtmax (hazard ratio: 1.024, p = 0.007) and the symptom duration (hazard ratio: 0.977, p = 0.003) were independent predictors of LV-RR. A receiver operating characteristic curve analysis revealed a ΔLVdP/dtmax cut-off value of 75.1% for LV-RR and a significantly lower cardiac event rate in the ΔLVdP/dtmax ≥ 75.1% group (p = 0.045). Conclusions ΔLVdP/dtmax estimated using DST was a useful predictor of LV-RR and cardiac events in patients with DCM.

    DOI: 10.1016/j.jjcc.2017.02.005

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  83. Sokolow-Lyon voltage is suitable for monitoring improvement in cardiac function and prognosis of patients with idiopathic dilated cardiomyopathy.

    Fukaya K, Takeshita K, Okumura T, Hiraiwa H, Aoki S, Ichii T, Sugiura Y, Kitagawa K, Kondo T, Watanabe N, Kano N, Furusawa K, Sawamura A, Morimoto R, Bando Y, Murohara T

    Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc   Vol. 22 ( 5 )   2017.9

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    Background: The clinical significance of electrocardiogram in the assessment of patients with idiopathic dilated cardiomyopathy (IDCM) is currently unknown. The aim of this study was to determine the feasibility of recording serial changes in Sokolow–Lyon voltage (∆%QRS-voltage) in one year to estimate left ventricular reverse remodeling (LVRR) and predict a prognosis of IDCM patients under tailored medical therapy. Methods: Sixty-eight consecutive patients with mild symptoms (52.1 ± 13 years old; 69% men; NYHA I/II/III/IV; 33/29/6/0) underwent electrocardiography and echocardiography at baseline and 12 month follow-up (follow-up period: 3.9 years). Results: LVRR was observed in 30 patients (44.1%). The ∆%QRS-voltage was significantly lower in the LVRR group (LVRR; −26.9%, non-LVRR: −9.2%, p <.001). Univariate analysis showed that ∆%QRS-voltage correlated with ∆%LV end-diastolic diameter (r =.634, p <.001), and with ∆%LV ejection fraction and ∆%LV mass index (r = −.412, p <.001; r =.429, p <.001 respectively). Using receiver operating characteristic curve analysis for the estimation of LVRR, ∆%QRS of −14.7% showed optimal sensitivity (63.2%) and specificity (83.3%) (AUC = 0.775, p <.001). The composite endpoints of cardiac death (n = 0), hospitalization for advanced heart failure (n = 11) and fatal arrhythmia (n = 2) were observed in 13 patients during the follow-up period. Kaplan–Meier analysis showed significantly higher event-free rate in patients of the low ∆%QRS-voltage group (<−14.7%) (83%) than those of the high group (66%, p =.022). Conclusions: The present study showed that decrease in Sokolow–Lyon voltage is associated with improvement in cardiac function and favorable prognosis in IDCM patients on medical therapy, suggesting that this index is a feasible marker for response to treatment of IDCM.

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  84. Is the administration of mineralocorticoid receptor antagonist required in asymptomatic AHA/ACC stage B heart failure patients?

    Okumura T., Sawamura A., Sugiura Y., Hiraiwa H., Kondo T., Aoki S., Watanabe N., Kano N., Fukaya K., Morimoto R., Bando Y. K., Murohara T.

    EUROPEAN HEART JOURNAL   Vol. 38   page: 698 - 698   2017.8

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  85. The Selvester QRS score as a predictor of cardiac events in nonischemic dilated cardiomyopathy

    Hiraiwa H., Okumura T., Sawamura A., Sugiura Y., Kondo T., Watanabe N., Aoki S., Ichii T., Kano N., Fukaya K., Furusawa K., Morimoto R., Takeshita K., Bando Y., Murohara T.

    EUROPEAN HEART JOURNAL   Vol. 38   page: 143 - 144   2017.8

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  86. Cholesterol metabolism as a prognostic marker in patients with mildly symptomatic nonischemic dilated cardiomyopathy.

    Sawamura A, Okumura T, Hiraiwa H, Aoki S, Kondo T, Ichii T, Furusawa K, Watanabe N, Kano N, Fukaya K, Morimoto R, Bando YK, Murohara T

    Journal of cardiology   Vol. 69 ( 6 ) page: 888 - 894   2017.6

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    Background Little is known about whether the alteration of cholesterol metabolism reflects abdominal organ impairments due to heart failure. Therefore, we investigated the prognostic value of cholesterol metabolism by evaluating serum campesterol and lathosterol levels in patients with early-stage nonischemic dilated cardiomyopathy (NIDCM). Methods We enrolled 64 patients with NIDCM (median age 57.5 years, 31% female) with New York Heart Association functional class I/II. Serum campesterol and lathosterol levels were measured in all patients. The patients were then divided into four subsets based on the median non-cholesterol sterol levels (campesterol 3.6 μg/mL, lathosterol 1.4 μg/mL): reference (R-subset), high-campesterol/high-lathosterol; absorption-reduced (A-subset), low-campesterol/high-lathosterol; synthesis-reduced (S-subset), high-campesterol/low-lathosterol; double-reduced (D-subset), low-campesterol/low-lathosterol. Endpoint was a composite of cardiac events, including cardiac-related death, hospitalization for worsening heart failure, and lethal arrhythmia. Results Median brain natriuretic peptide (BNP) level was 114 pg/mL. Mean left ventricular ejection fraction was 31.4%. D-subset had the lowest total cholesterol level and cardiac index and the highest BNP level and pulmonary capillary wedge pressure. D-subset also had the highest cardiac event rate during the mean 3.8 years of follow-up (log-rank p = 0.001). Multivariate regression analysis showed that D-subset was an independent determinant of cardiac events. The receiver operating characteristic curve analysis revealed that total cholesterol <153 mg/dL was a best cut-off value for discrimination of the D-subset. Conclusions The combined reduction of campesterol and lathosterol that indicated intestinal cholesterol absorption and liver synthesis predicts future cardiac events in patients with mildly symptomatic NIDCM.

    DOI: 10.1016/j.jjcc.2016.08.012

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  87. Long-Term Pathological Follow-Up of Myocardium in a Carrier of Duchenne Muscular Dystrophy With Dilated Cardiomyopathy.

    Kondo T, Okumura T, Takefuji M, Hiraiwa H, Sugiura Y, Watanabe N, Aoki S, Ichii T, Kitagawa K, Kano N, Fukaya K, Furusawa K, Sawamura A, Morimoto R, Bando YK, Takemura G, Murohara T

    Circulation. Heart failure   Vol. 10 ( 3 ) page: e003826   2017.3

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    DOI: 10.1161/CIRCHEARTFAILURE.117.003826

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Books 1

  1. 特集 エキスパートに学ぶ 最新の循環器治療薬の使い方 知っておくべき10種類の循環器治療薬と治療法 心不全に対する新規治療薬 4-HCNチャネル遮断薬 コララン Reviewed

    奥村 貴裕, 荒木 孝, 平岩 宏章( Role: Joint author)

    medicina  2021.1 

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    Language:Japanese Book type:Textbook, survey, introduction

    DOI: 10.11477/mf.1402227378

MISC 18

  1. Dilated cardiomyopathy with anti-mitochondrial M2 antibody: A case series.

    Kazama S, Kondo T, Ito R, Kimura Y, Kuwayama T, Hiraiwa H, Morimoto R, Okumura T, Murohara T

    Journal of cardiology cases   Vol. 28 ( 1 ) page: 11 - 15   2023.7

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    Patients with dilated cardiomyopathy (DCM) sometimes show anti-mitochondrial M2 antibody (AMA-M2) positivity. We aimed to compare the characteristics of DCM cases with and without AMA-M2, and to describe cases of DCM with AMA-M2 positivity. A total of 84 patients with DCM were analyzed. Six patients (7.1 %) were positive for AMA-M2. Of these six patients, five (83.3 %) had primary biliary cirrhosis (PBC) and four (66.7 %) had myositis. Patients with AMA-M2 positivity had more atrial fibrillation and more premature ventricular contractions than those without. Left and right atrial longitudinal dimensions were larger in patients with AMA positivity (left atrium, 65.9 mm vs. 54.7 mm, p = 0.02; right atrium, 57.0 mm vs. 46.1 mm, p = 0.02). Of the six patients with AMA-M2 positivity, three underwent cardiac resynchronization therapy with defibrillator implantation and three required catheter ablation treatment. Steroids were used in three patients. One patient died of unresolved lethal arrhythmia and another required re-hospitalization for heart failure; the remaining four patients did not have adverse events. Patients with DCM with AMA-M2 positivity had a higher affinity for PBC and myositis than those without, and are characterized by atrial enlargement and arrhythmias. Learning objective: Patients with dilated cardiomyopathy sometimes exhibit anti-mitochondrial M2 antibody positivity. These patients are at higher risk for primary biliary cirrhosis and inflammatory myositis, and their cardiac disorders are characterized by atrial enlargement and various arrhythmias. The course of the disease up to the time of diagnosis and after steroid use varies, and the prognosis is poor in advanced cases.

    DOI: 10.1016/j.jccase.2023.02.021

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  2. Contractile pericarditis-like hemodynamics in dilated-phase hypertrophic cardiomyopathy with giant atrium.

    Morimoto R, Ito R, Araki T, Mizutani T, Kimura Y, Kazama S, Oishi H, Kuwayama T, Sugiura Y, Hiraiwa H, Kondo T, Okumura T, Kobayashi K, Mutsuga M, Murohara T

    Journal of cardiology cases   Vol. 27 ( 5 ) page: 199 - 202   2023.5

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    A 47-year-old man with dilated-phase hypertrophic cardiomyopathy was admitted to the hospital with worsening heart failure. As the enlarged atrium caused a constrictive pericarditis-like hemodynamic condition, atrial wall resection and tricuspid valvuloplasty were performed. Postoperatively, pulmonary artery pressure rose due to increased preload; however, the rise in pulmonary artery wedge pressure was restrained, and the cardiac output significantly improved. When the pericardium is extremely stretched due to atrial enlargement, it can lead to an elevation of intrapericardial pressure, and both atrial volume reduction and tricuspid valve plasty could lead to increased compliance and contribute to hemodynamic improvement. Learning objective: Atrial wall resection for massive atrial enlargement and tricuspid annuloplasty in patients with diastolic-phase hypertrophic cardiomyopathy effectively relieves unstable hemodynamics.

    DOI: 10.1016/j.jccase.2023.01.005

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  3. Cardiac Rehabilitation in Severe Heart Failure Patients with Impella 5.0 Support via the Subclavian Artery Approach Prior to Left Ventricular Assist Device Implantation.

    Shimizu M, Hiraiwa H, Tanaka S, Tsuchikawa Y, Ito R, Kazama S, Kimura Y, Araki T, Mizutani T, Oishi H, Kuwayama T, Kondo T, Morimoto R, Okumura T, Ito H, Yoshizumi T, Mutsuga M, Usui A, Murohara T

    Journal of personalized medicine   Vol. 13 ( 4 )   2023.4

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    Impella 5.0 circulatory support via subclavian artery (SA) access may be a safe approach for patients undergoing cardiac rehabilitation (CR). In this case series, we retrospectively analyzed the demographic characteristics, physical function, and CR data of six patients who underwent Impella 5.0 implantation via the SA prior to left ventricular assist device (LVAD) implantation between October 2013 and June 2021. The median age was 48 years, and one patient was female. Grip strength was maintained or increased in all patients before LVAD implantation (pre-LVAD) compared to after Impella 5.0 implantation. The pre-LVAD knee extension isometric strength (KEIS) was less than 0.46 kgf/kg in two patients and more than 0.46 kgf/kg in three patients (unavailable KEIS data, n = 1). With Impella 5.0 implantation, two patients could ambulate, one could stand, two could sit on the edge of the bed, and one remained in bed. One patient lost consciousness during CR due to decreased Impella flow. There were no other serious adverse events. Impella 5.0 implantation via the SA allows mobilization, including ambulation, prior to LVAD implantation, and CR can be performed relatively safely.

    DOI: 10.3390/jpm13040630

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  4. A Case of Systemic Capillary Leak Syndrome With Severe Cardiac Dysfunction After mRNA Vaccination for COVID-19.

    Araki T, Morimoto R, Ito R, Mizutani T, Kimura Y, Kazama S, Oishi H, Kuwayama T, Hiraiwa H, Kondo T, Okumura T, Murohara T

    CJC open   Vol. 4 ( 7 ) page: 656 - 659   2022.7

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    A 53-year-old woman with no significant medical history developed cardiogenic shock 4 days after receiving the second dose of the COVID-19 mRNA vaccine (BNT162b2, Pfizer/BioNtech). The patient required extracorporeal membrane oxygenation and an Impella device. Based on significant hemoconcentration, decreased plasma protein levels, and pathologic findings in myocardial specimens, the patient was diagnosed with vaccination-induced fulminant systemic capillary leak syndrome (SCLS) with severe cardiac dysfunction. This case highlights that SCLS can occur after COVID-19 mRNA vaccination and may be associated with cardiac dysfunction. In patients with cardiogenic shock, hemoconcentration, and hypoalbuminemia after vaccination, SCLS should be considered.

    DOI: 10.1016/j.cjco.2022.03.008

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  5. Recurrent fulminant non-rheumatic streptococcal myocarditis proven by endomyocardial biopsy and autopsy.

    Hiraiwa H, Morimoto R, Ando R, Ito R, Araki T, Mizutani T, Kazama S, Kimura Y, Oishi H, Kuwayama T, Yamaguchi S, Kondo T, Okumura T, Enomoto A, Murohara T

    Journal of cardiology cases   Vol. 26 ( 1 ) page: 62 - 65   2022.7

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    A 42-year-old man with a history of acute myocarditis after streptococcal pharyngitis developed recurrent fulminant myocarditis. Endomyocardial biopsy revealed myocyte degeneration, interstitial edema, and neutrophil infiltration. The patient's cardiac function deteriorated rapidly, and he died despite mechanical circulatory support. Autopsy revealed neutrophil infiltration, interstitial edema, and micro-abscesses containing masses of streptococci and neutrophilic phagocytosis within the myocardium. The patient did not meet the diagnostic criteria for acute rheumatic fever; thus, he was diagnosed with non-rheumatic streptococcal myocarditis. Non-rheumatic streptococcal myocarditis rarely recurs, but it can be fulminant upon recurrence. Learning objective: We report a rare case of recurrent fulminant non-rheumatic streptococcal myocarditis. Endomyocardial biopsy and autopsy revealed neutrophil infiltration and micro-abscesses containing bacterial masses of streptococci and neutrophilic phagocytosis in the myocardium. The patient did not meet the diagnostic criteria for acute rheumatic fever; thus, he was diagnosed with non-rheumatic streptococcal myocarditis. Non-rheumatic streptococcal myocarditis rarely recurs, but it can be fulminant upon recurrence.

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  6. Biopsy-Proven Fulminant Myocarditis Requiring Mechanical Circulatory Support Following COVID-19 mRNA Vaccination.

    Kazama S, Okumura T, Kimura Y, Ito R, Araki T, Mizutani T, Oishi H, Kuwayama T, Hiraiwa H, Kondo T, Morimoto R, Saeki T, Murohara T

    CJC open   Vol. 4 ( 5 ) page: 501 - 505   2022.5

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    A 48-year-old woman suffered from cardiogenic shock with fulminant myocarditis following the second dose of COVID-19 vaccine (mRNA-1273). Venoarterial extracorporeal membrane oxygenation and Impella support were essential in achieving hemodynamic stability. Endomyocardial biopsy revealed lymphocytic infiltration with predominant immunostaining for CD8- and CD68-positive cells. The left ventricular ejection fraction improved significantly after treatment with mechanical circulatory support. Myocarditis following COVID-19 mRNA vaccination may also occur in middle-aged women; it may be fulminant and require mechanical circulatory support. Although our results suggest the involvement of cytotoxic T lymphocytes and macrophages, further investigation is needed before these can be established as pathogenetic mechanisms.

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  7. Bedside cannulation for veno-venous extracorporeal membrane oxygenation using portable X-ray system in a coronavirus disease patient.

    Kondo T, Kuwayama T, Hiraiwa H, Kasugai D, Goto Y, Numaguchi A, Katsu T, Matsui T, Hashimoto N, Tanaka A, Morimoto R, Okumura T, Murohara T

    Journal of cardiology cases   Vol. 25 ( 3 ) page: 185 - 187   2022.3

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    Transportation of patients with coronavirus disease (COVID)-19 outside isolation rooms should be avoided to prevent further spread of the disease. Here, we report a safe and accurate bedside cannulation method for veno-venous extracorporeal membrane oxygenation (VV-ECMO) in a COVID-19 patient in the intensive care unit. A 71-year-old man was admitted to our hospital and diagnosed as having COVID-19 pneumonia. We decided to initiate VV-ECMO therapy because maintaining blood oxygen saturation was difficult despite the mechanical ventilation. We placed two flat-panel detectors behind the patient's chest and the right inguinal area. We repeatedly imaged and monitored insertion of wires and cannulas using a portable X-ray system. Cannulas were successfully inserted in the appropriate position, and VV-ECMO was initiated without any complications. <Learning objective: Transportation of patients with coronavirus disease outside isolation rooms carries the risk of further spread of the disease. By repeatedly acquiring images using a portable X-ray system, safe and accurate cannulation for veno-venous extracorporeal membrane oxygenation cannulation can be performed at the bedside in the intensive care unit.>

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  8. Two cases of dilated cardiomyopathy with blood pressure-limited tolerability of cardioprotective agents improved by ivabradine.

    Okumura T, Hiraiwa H, Araki T, Mizutani T, Kimura Y, Kazama S, Shibata N, Oishi H, Kuwayama T, Kondo T, Morimoto R, Murohara T

    Journal of cardiology cases   Vol. 23 ( 4 ) page: 149 - 153   2021.4

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    The titration of cardioprotective agents is essential for successful treatment of heart failure (HF) patients with reduced left ventricular ejection fraction. However, hypotension is one of the limiting factors for titration. Ivabradine reduces heart rate without compromising systolic function by prolonging diastolic filling time. Herein two cases of dilated cardiomyopathy (DCM) are presented in which ivabradine improved blood pressure (BP)-limited tolerability and allowed for further titration of cardioprotective agents. In both cases, the introduction of ivabradine raised the BP, which permitted further increase of the dose of renin-angiotensin system inhibitors or beta-blockers. One major hypothesized mechanism of ivabradine-induced BP elevation has been postulated to be an increase in stroke volume due to prolonged ventricular diastolic filling time. However, ivabradine is not expected to increase BP for all HF patients. In those with small and poorly compliant ventricles with severe diastolic or restricted dysfunction, decreased heart rate and prolonged diastole may excessively suppress compensatory mechanisms, and thus may not lead to increased cardiac output and BP. In contrast, ivabradine potentially increases BP and improves BP-limited tolerability of cardioprotective agents in DCM patients with a large and compliant heart. In addition, subsequent titration of cardioprotective agents may provide additional cardiac reverse remodeling. Learning objective: Ivabradine is usually used for heart failure patients with reduced ejection fraction when the tolerability of cardioprotective agents is maximized. This agent has no direct cardiac contractility-suppressing action. It potentially increases blood pressure and improves tolerability of cardioprotective agents in patients with a large and compliant heart such as dilated cardiomyopathy. Furthermore, subsequent titration of cardioprotective agents may provide additional cardiac reverse remodeling.

    DOI: 10.1016/j.jccase.2020.11.007

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  9. A case of reexpansion pulmonary edema and acute pulmonary thromboembolism associated with diffuse large B-cell lymphoma treated with venovenous extracorporeal membrane oxygenation.

    Kazama S, Hiraiwa H, Kimura Y, Ozaki R, Shibata N, Arao Y, Oishi H, Kato H, Kuwayama T, Yamaguchi S, Kondo T, Furusawa K, Morimoto R, Okumura T, Bando YK, Sato T, Shimada K, Kiyoi H, Nakamura G, Yasuda Y, Kasugai D, Ogawa H, Higashi M, Yamamoto T, Jingushi N, Ozaki M, Numaguchi A, Goto Y, Matsuda N, Murohara T

    Journal of cardiology cases   Vol. 23 ( 1 ) page: 53 - 56   2021.1

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    A 37-year-old man diagnosed with diffuse large B-cell lymphoma two weeks previously, visited our emergency department with sudden dyspnea. He had a severe respiratory failure with saturated percutaneous oxygen at 80% (room air). Chest radiography showed a large amount of left pleural effusion. After 1000 mL of the effusion was urgently drained, reexpansion pulmonary edema (RPE) occurred. Despite ventilator management, oxygenation did not improve and venovenous extracorporeal membrane oxygenation (VV-ECMO) was initiated in the intensive care unit. The next day, contrast-enhanced computed tomography showed a massive thrombus in the right pulmonary artery, at this point the presence of pulmonary thromboembolism (PTE) was revealed. Fortunately, the patient's condition gradually improved with anticoagulant therapy and VV-ECMO support. VV-ECMO was successfully discontinued on day 4, and chemotherapy was initiated on day 8. We speculated the following mechanism in this case: blood flow to the right lung significantly reduced due to acute massive PTE, and blood flow to the left lung correspondingly increased, which could have caused RPE in the left lung. Therefore, our observations suggest that drainage of pleural effusion when contralateral blood flow is impaired due to acute PTE may increase the risk of RPE. <Learning objective: This is a case of reexpansion pulmonary edema (RPE) in the left lung following acute pulmonary thromboembolism (PTE) in the right lung associated with malignant lymphoma, managed by venovenous extracorporeal membrane oxygenation. Contralateral pleural drainage could increase the risk of RPE because contralateral pulmonary blood flow is assumed to increase when PTE obstructs blood flow. Pleural drainage should be performed carefully in patients with malignant tumors because PTE may be hidden.>

    DOI: 10.1016/j.jccase.2020.08.013

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  10. Relative bradycardia as a clinical feature in patients with coronavirus disease 2019 (COVID-19): A report of two cases.

    Hiraiwa H, Goto Y, Nakamura G, Yasuda Y, Sakai Y, Kasugai D, Jinno S, Tanaka T, Ogawa H, Higashi M, Yamamoto T, Jingushi N, Ozaki M, Numaguchi A, Kondo T, Morimoto R, Okumura T, Matsuda N, Murohara T

    Journal of cardiology cases   Vol. 22 ( 6 ) page: 260 - 264   2020.12

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    We treated two patients with COVID-19 pneumonia requiring mechanical ventilation. Case 1 was a 73-year-old Japanese man. Computed tomography (CT) revealed ground-glass opacities in both lungs. He had severe respiratory failure with a partial pressure of oxygen in arterial blood/fraction of inspiratory oxygen ratio (P/F ratio) of 203. Electrocardiogram showed a heart rate (HR) of 56 beats/min, slight ST depression in leads II, III, and aVF, and mild saddle-back type ST elevation in leads V1 and V2. High-sensitivity cardiac troponin T (cTnT) level was slightly elevated. Despite a high fever and hypoxemia, his HR remained within 50–70 beats/min. Case 2 was a 52-year-old Japanese woman. CT revealed ground-glass opacities in the lower left lung. Electrocardiogram showed a HR of only 81 beats/min, despite a body temperature of 39.2 °C, slight ST depression in leads V4, V5, V6, and a prominent U wave in multiple leads. She had an elevated cTnT and a P/F ratio of 165. Despite a high fever and hypoxemia, her HR remained within 50–70 beats/min. Both patients had a poor compensatory increase in their HR, despite their critical status. Relative bradycardia could be a cardiovascular complication and is an important clinical finding in patients with COVID-19. <Learning objective: We report two Japanese cases of COVID-19 pneumonia with relative bradycardia as a condition and no significant compensatory increase in heart rate despite high fever and severe hypoxemia. Relative bradycardia in COVID-19 might be associated with myocardial injury due to not only direct viral involvement but also systemic inflammation. We should carefully observe the occurrence of relative bradycardia because it could potentially be a clinical sign of COVID-19.>

    DOI: 10.1016/j.jccase.2020.07.015

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  11. Impella 5.0 for Cardiogenic Shock After Thrombectomy in a Patient With Intraventricular Thrombosis.

    Kimura Y, Kondo T, Mutsuga M, Morimoto R, Kazama S, Shibata N, Oishi H, Arao Y, Kuwayama T, Kato H, Yamaguchi S, Hiraiwa H, Okumura T, Fujimoto K, Usui A, Murohara T

    The Canadian journal of cardiology   Vol. 36 ( 10 ) page: 1690.e13 - 1690.e15   2020.10

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    A 43-year-old man was admitted to a referring hospital for cardiogenic shock caused by dilated cardiomyopathy. Intra-aortic balloon pump and percutaneous venoarterial extracorporeal membrane oxygenation (VA-ECMO) were started initially; however, a thrombus was detected in the left ventricle. After transfer to our institution, we performed thrombectomy through minithoracotomy. Subsequently, an Impella 5.0 device was inserted via the left subclavian artery. His cardiac function gradually improved, and both VA-ECMO and the Impella 5.0 could be weaned off. He was discharged without any thromboembolic event. Impella insertion with thrombectomy was possible, minimally invasive, and effective for a patient with intraventricular thrombosis associated with VA-ECMO.

    DOI: 10.1016/j.cjca.2020.04.005

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  12. Differential Diagnosis of Mechanisms of Exercise-Induced Abnormal Blood Pressure Response in Hypertrophic Cardiomyopathy Without Left Ventricular Outflow Tract Obstruction.

    Okumura T, Kano N, Sawamura A, Kondo T, Hiraiwa H, Morimoto R, Murohara T

    Circulation. Heart failure   Vol. 13 ( 10 ) page: e007164 - 551   2020.10

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    DOI: 10.1161/CIRCHEARTFAILURE.120.007164

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  13. Fulminant myocarditis with myositis of ocular and respiratory muscles.

    Hiraiwa H, Furusawa K, Kazama S, Kimura Y, Shibata N, Arao Y, Oishi H, Kato H, Kuwayama T, Yamaguchi S, Kondo T, Sawamura A, Morimoto R, Okumura T, Murohara T

    Nagoya journal of medical science   Vol. 82 ( 3 ) page: 585 - 593   2020.8

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    A 46-year-old Japanese woman visited a nearby hospital because of diplopia after flu-like symptoms. One month later, she presented with blepharoptosis and external ophthalmoplegia. Laboratory tests showed a high creatine kinase concentration (3146 U/L). She underwent intravenous immunoglobulin therapy; however, her symptoms did not improve, prompting transfer to our institute. On admission, transthoracic echocardiography revealed 30% of left ventricular ejection fraction and edema of the left ventricular wall. Coronary angiography showed no significant coronary stenosis. An endomyocardial biopsy resulted in a diagnosis of acute myocarditis. On the following day, she needed a temporary pacemaker because she had complete atrioventricular block and intra-aortic balloon pump because of cardiogenic shock. Intravenous immunoglobulin therapy was again administered and her cardiac function gradually recovered. She was successfully weaned off her temporary pacemaker and intra-aortic balloon pump on Day 5 after improvement in her complete atrioventricular block. Steroid therapy administered from Day 9 was effective in reducing her creatine kinase concentrations. However, contrast-enhanced magnetic resonance imaging revealed inflammation of the scalene, semispinalis cervicis, sternocleidomastoid, and intercostal muscles. On Day 25, her cardiac function had recovered to a left ventricular ejection fraction of 59%. Finally, she was successfully discharged on Day 45 after undergoing rehabilitation.

    DOI: 10.18999/nagjms.82.3.585

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  14. Pathological changes of the myocardium in reworsening of anthracycline-induced cardiomyopathy after explant of a left ventricular assist device.

    Hiraiwa H, Okumura T, Shimizu S, Arao Y, Oishi H, Kato H, Kuwayama T, Yamaguchi S, Haga T, Yokoi T, Kondo T, Sugiura Y, Kano N, Watanabe N, Fukaya K, Furusawa K, Sawamura A, Morimoto R, Fujimoto K, Mutsuga M, Usui A, Murohara T

    Nagoya journal of medical science   Vol. 82 ( 1 ) page: 129 - 134   2020.2

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    We herein report the long-term changes in cardiac function and pathological findings after successful explantation of a left ventricular assist device in a 42-year-old patient with anthracycline-induced cardiomyopathy with reworsening heart failure. Endomyocardial biopsy samples revealed that the cardiomyocyte diameter decreased and collagen volume fraction increased just after left ventricular assist device explantation. The collagen volume fraction decreased after 6 months, despite preserved systolic function. At 5 years after left ventricular assist device explantation, the systolic function markedly decreased and cardiomyocyte diameter increased. Pathological changes of the myocardium may enable the identification of cardiac dysfunction prior to echocardiographic changes in patients with reworsening heart failure after left ventricular assist device explantation.

    DOI: 10.18999/nagjms.82.1.129

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  15. Giant cell myocarditis with central diabetes insipidus: A case report.

    Yamaguchi S, Sawamura A, Nakaguro M, Shimoyama Y, Morimoto R, Kato H, Arao Y, Oishi H, Haga T, Kuwayama T, Yokoi T, Hiraiwa H, Kondo T, Okumura T, Murohara T

    Journal of cardiology cases   Vol. 21 ( 1 ) page: 8 - 11   2020.1

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    A 51-year-old male, previously diagnosed with central diabetes insipidus due to lymphocytic hypophysitis, presented with fever and dyspnea for 1 week. On arrival, he exhibited hypotension (85/60 mmHg) and sinus tachycardia (110 bpm). His electrocardiogram revealed mild ST elevation on V2–V4. Echocardiography indicated a near-normal (50%) left ventricular ejection fraction (LVEF), although the inferior wall of the left ventricle exhibited severe hypokinesis. Fulminant myocarditis and circulatory insufficiency were suspected, and treatment with dobutamine, 3 μg/kg/min, was started. His LVEF gradually decreased to 20%. On day 17, he developed cardiogenic shock due to ventricular tachycardia and underwent peripheral venous–arterial extracorporeal membrane oxygenation and intra-aortic balloon pumping. Although he did not exhibit polyuria, intravenous vasopressin infusion (0.5 U/h) was performed to maintain normonatremia. Endomyocardial biopsy results revealed the infiltration of scattered giant cells (GCs) and extensive lymphocytes. Despite immunosuppressive therapy (methylprednisolone and cyclosporine), his cardiac function did not recover. On day 36, he received a biventricular assist device; however, he died on day 47 due to the progression of sepsis and multiple organ failure. We speculate that a deficient expression of programmed cell death protein-1 was the cause of both GC myocarditis and lymphocytic hypophysitis. <Learning objective: We describe a fatal case of fulminant giant cell myocarditis complicated by central diabetes insipidus due to lymphocytic hypophysitis. Normonatremia was maintained with intravenous vasopressin 0.5 U/h, and circulatory status was maintained with mechanical circulatory support. We speculate that T-cell programmed cell death protein 1 dysregulation was the common cause of the two disorders.>

    DOI: 10.1016/j.jccase.2019.08.011

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  16. A survival case of a young adult patient with ST-elevated myocardial infarction with high levels of lipoprotein(a).

    Hiraiwa H, Morimoto R, Okumura T, Arao Y, Oishi H, Kato H, Yamaguchi S, Kuwayama T, Haga T, Yokoi T, Kondo T, Watanabe N, Mitsuda T, Fukaya K, Sawamura A, Tanaka A, Ishii H, Morishima I, Tsuboi H, Murohara T

    Journal of cardiology cases   Vol. 19 ( 6 ) page: 207 - 210   2019.6

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    A 23-year-old Japanese man presented to a nearby hospital with a complaint of chest pain. In terms of the risk factors for cardiovascular events, there were no abnormal findings in past medical examinations and no smoking history. The 12-lead electrocardiogram revealed ST-elevation in V1-V6, I, and aVL, and he was diagnosed with acute myocardial infarction. Emergency coronary angiography findings revealed total occlusion of the left main trunk and collateral vessels from the right coronary artery to the left anterior descending artery. He underwent emergency percutaneous coronary intervention and placement of drug-eluting stent under the support of venoarterial-extracorporeal membrane oxygenator (VA-ECMO). On day 8 after the onset, transthoracic echocardiography revealed that cardiac function improved with left ventricular ejection fraction from 10% to 20% and VA-ECMO was successfully removed. Alternatively, laboratory findings revealed abnormally high levels of serum lipoprotein(a) [Lp(a), 74 mg/dL] despite the normal levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride. In addition, computed tomography angiography revealed atherosclerosis and stenosis of internal and external carotid arteries, subclavian artery, and renal artery. The abnormally high levels of serum Lp(a) could influence systemic atherosclerosis as well as the onset of myocardial infarction in our young adult patient. <Learning objective: This was a rare survival case of a young adult patient with acute extensive myocardial infarction owing to plaque rupture of the left main trunk. Additionally, he had atherosclerosis of the whole body, including the carotid artery, subclavian artery, and renal artery. Blood test results revealed abnormally high levels of serum lipoprotein(a) [Lp(a)] despite the normal levels of low-density lipoprotein cholesterol. Lp(a) could strongly influence coronary atherosclerosis and myocardial infarction.>

    DOI: 10.1016/j.jccase.2019.02.004

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  17. Hemodynamics of cardiac tamponade during extracorporeal membrane oxygenation support in a patient with fulminant myocarditis.

    Kondo T, Morimoto R, Yokoi T, Yamaguchi S, Kuwayama T, Haga T, Hiraiwa H, Sugiura Y, Watanabe N, Kano N, Ichii T, Fukaya K, Sawamura A, Okumura T, Yoshizumi T, Mutsuga M, Fujimoto K, Matsuda N, Usui A, Murohara T

    Journal of cardiology cases   Vol. 19 ( 1 ) page: 22 - 24   2019.1

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    Fulminant myocarditis (FM) causes rapid onset severe heart failure requiring inotropes or mechanical circulatory support. Myocarditis is sometimes associated with pericardial effusion, however, how this effusion affects the hemodynamics in patients with FM under venoarterial extracorporeal membrane oxygenation (VA-ECMO) management has not been fully reported. We show a case of FM presenting with cardiac tamponade during VA-ECMO management. A 64-year-old female diagnosed as having FM showed a rapid hemodynamic collapse and that led to the application of VA-ECMO. Although her left ventricular ejection fraction did not improve despite proper hemodynamics management for several days, a pericardial effusion accumulated gradually. Apparent elevation of right atrial pressure and reduction of blood pressure were not observed, however, we performed pericardiocentesis because we were not able to wean off VA-ECMO. After the drainage of pericardial effusion, the blood pressure and cardiac output elevated as did the left ventricular ejection fraction. We successfully removed VA-ECMO and the patient was discharged without any complications. This is a case report in which a cardiac tamponade under VA-ECMO did not show typical signs and pericardiocentesis contributed to withdrawal of a VA-ECMO system. <Learning objective: Typical findings of cardiac tamponade are less likely to appear in patients with fulminant myocarditis under venoarterial extracorporeal membrane oxygenation management (VA-ECMO). Drainage of pericardial effusion delivers dramatic improvement in blood pressure, cardiac output, and left ventricular ejection fraction. When VA-ECMO cannot be weaned off, pericardiocentesis should be considered in patients with fulminant myocarditis who showed gradual accumulation of pericardial effusion.>

    DOI: 10.1016/j.jccase.2018.08.009

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  18. Promising method for management of venoarterial extracorporeal membrane oxygenation: A case of severe heart failure successfully stabilized by "high-flow/vasodilation method".

    Kondo T, Sawamura A, Okumura T, Kano N, Morimoto R, Watanabe N, Hiraiwa H, Kuwayama T, Sugiura Y, Haga T, Yamaguchi S, Fukaya K, Yokoi T, Fujimoto K, Mutsuga M, Yoshizumi T, Matsuda N, Usui A, Murohara T

    Journal of cardiology cases   Vol. 18 ( 2 ) page: 81 - 84   2018.8

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    We report the case of a 58-year-old man with dilated cardiomyopathy who was hospitalized because of worsening heart failure. As his symptoms were refractory even with the administration of inotropes, he was given peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) upon transfer to our hospital. On admission, serum creatinine was 2.62 mg/dL and total bilirubin 10.8 mg/dL. The cannulas inserted were 16-Fr for infusion and 21-Fr for drainage. When the blood flow was increased to 2.14 L/min/m2 to improve organ dysfunction, the aortic valve became continuously close with the mean arterial pressure of 85 mmHg. Therefore, we administrated vasodilators to decrease mean arterial pressure, or left ventricular afterload, which achieved opening aortic valve continuously. After the cannula sizes were scaled up to 18Fr for infusion and 24Fr for drainage to gain further blood flow, the aortic valve opened continuously and mean pulmonary pressure decreased. Our strategy to maintain adequate flow rate of VA-ECMO using vasodilator, “high-flow/vasodilation method” achieved hemodynamic stability. Additionally, the concentration of serum creatinine and total bilirubin gradually decreased to within the normal range, although the patient succumbed 58 days after transfer to our hospital. <Learning objective: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is often used as a first-line mechanical circulatory support in patients with severe heart failure. However, its management is difficult and not established. We discuss the efficacy and potency of our “high-flow/vasodilation method” in the management of VA-ECMO.>

    DOI: 10.1016/j.jccase.2018.05.002

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KAKENHI (Grants-in-Aid for Scientific Research) 2

  1. 心脾連関に注目した新しい心不全治療法の開発

    Grant number:21K16085  2021.4 - 2026.3

    日本学術振興会  科学研究費助成事業  若手研究

    平岩 宏章

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    Authorship:Principal investigator 

    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

    心不全は未だ致死的な疾患の一つであり、個別化医療を含めた新規治療法の開発の社会的ニーズは非常に高い。
    近年、心不全において心臓と他臓器の連関が注目されているが、脾臓との連関(心脾連関)については未解明の部分が多い。一方、脾臓には様々な役割があるが、組織マクロファージを介した心脾連関に注目した先行研究はない。また、心不全における脾臓の生理学的な役割も十分解明されていない。
    本研究は、心不全における多臓器連関の中での脾臓の機能多様性や、病態との関連を明らかにし、さらには、心不全における新たなバイオマーカやモニタリングの開発や、心脾連関への介入を念頭においた新規の心不全治療法の開発を目指した研究である。
    本研究は、心不全における脾臓の未解明の役割、特に多臓器連関の中での脾臓の機能多様性を探索し検証することを目的としている。これまでに研究代表者は、左室補助人工心臓(LVAD)を要する重症心不全で、脾臓容積は増大し、LVAD不良による心不全増悪に伴い脾臓容積は速やかに減少することを報告し、重症心不全において脾臓は有効循環血漿量を調節している可能性を示した。また、脾臓容積はLVAD装着患者の拍出指数(Pulsatility Index)と関連し、自己心拍出量に寄与している可能性を示した。さらに、脾臓容積と運動耐容能の関連について検討した。運動耐容能指標である最高酸素摂取量(PeakVO2)に影響を与える因子の相関・因果関係を共分散構造解析(SEM)を用いて検討し、脾臓容積はLVAD装着患者の血中ヘモグロビンを介して、PeakVO2と関連することを示した。また、慢性心不全患者219人のデータを後ろ向きに解析し、脾臓容積と予後の関連について検討した。 患者集団は、年齢54歳、男性66%、NYHA3が9%、LVEF42%であった(中央値)。主要アウトカムは、複合心臓イベント(心臓死および心不全増悪入院)とした。結果、脾臓容積の中央値は、118.0mLであり。脾臓容積指数(SVI)は心拍出量および一回心拍出量と正の相関を示し、全身血管抵抗とは負の相関を示した。心イベント予測のための最適なSVIのカットオフ値は68.9 mL/m2であり、低SVI 群は高SVI群よりも、心イベントが多かった。ここまでのまとめとして、The cardiosplenic axis: the prognostic role of the spleen in heart failure と題したReview論文を報告した。現在、心不全における脾臓での髄外造血に注目した心臓、脾臓、骨髄の臓器連関について、検証中である。
    これまでに、心不全患者における脾臓容積と血行動態、運動耐容能、予後との関係を、臨床データを用いて検討した。その結果、特に心不全においては神経体液性因子および交感神経活動の活性化に伴い、その大きさを変化させ、構造的リモデリングを生じ、有効循環血漿量を調節している可能性が示唆された。すなわち心脾連関において、マクロの視点から脾臓の役割の一部を明らかにした。さらには、文献的考察から、脾臓から動員される免疫細胞やマクロファージが、心筋組織へ影響を与えることを示し、脾臓の機能的リモデリングの側面と合わせて、心脾連関の全体の概要についてレビューを行った。
    今後の研究内容として、引き続きミクロの視点から心脾連関のメカニズムについて検討する方針である。構造的リモデリングを生じた脾臓は機能的リモデリングを来し、脾臓からマクロファージや単球などの免疫細胞が血液中に放出される。脾臓由来の免疫細胞は、心臓に対して、心保護的な作用と逆の作用の両方を示す可能性がある。例えば、心臓固有のマクロファージと脾臓由来のマクロファージのバランスが心不全における慢性炎症の持続や線維化に影響を及ぼしている可能性がある。これらのメカニズムを、動物モデルを用いて検討していく予定である。さらには、近年、クローン性造血が心不全をはじめとする心血管疾患発症の病態に関与していることが報告されている。クローン性造血は、心筋の線維化を引き起こし、駆出率が維持された心不全(HFpEF)の病態を生じうる。HFpEFは高齢化と関連しているが、HFpEFに対する治療法はほとんど進歩していないのが現状である。このため、HFpEFにおける心臓、脾臓、さらには骨髄の臓器連関の概念について、免疫細胞の関与も含む髄外造血に焦点を当て、検証していく。また、脾臓がHFpEFの新たな治療ターゲットとなり得るかどうかも検証していく。

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  2. Development of novel treatment for fulminant myocarditis focusing on immune checkpoint molecules

    Grant number:19K23843  2019.8 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Research Activity Start-up

    Hiraiwa Hiroaki

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    Authorship:Principal investigator 

    Grant amount:\1430000 ( Direct Cost: \1100000 、 Indirect Cost:\330000 )

    This study investigated the relationship between T cell markers and PD-L1 expression in myocardial tissue and the prognosis of patients with fulminant lymphocytic myocarditis (FM). We analyzed 16 FM patients and found that the number of CD8+ T cells and CD8+/CD4+ T cell ratio were significantly higher in the group with cardiac events (composite of cardiac death and left ventricular assist device implantation). Additionally, the number of FoxP3+ T cells was higher in the cardiac event group, and PD-L1 expression in myocardial cells was also higher in the same group. Kaplan-Meier survival analysis revealed that high CD8+ T cell count or high PD-L1 expression in the myocardium could be poor prognostic factors in FM. Combining the expression of CD8+ T cells and PD-L1 could potentially help stratify the risk of cardiac events in FM. This study provides new insights into the mechanism and prognosis of fatal FM, which could aid in the development of new treatment strategies in the future.

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