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  • 1.
    Imamura, Teruhiko
    et al.
    University of Tokyo, Japan .
    Kinugawa, Koichiro
    University of Tokyo, Japan .
    Kato, Naoko
    University of Tokyo, Japan .
    Kagami, Yukie
    University of Tokyo, Japan .
    Endo, Miyoko
    University of Tokyo, Japan .
    Kaneko, Nobuyuki
    University of Tokyo, Japan .
    Minatsuki, Shun
    University of Tokyo, Japan .
    Muraoka, Hironori
    University of Tokyo, Japan .
    Inaba, Toshiro
    University of Tokyo, Japan .
    Maki, Hisataka
    University of Tokyo, Japan .
    Hatano, Masaru
    University of Tokyo, Japan .
    Doi, Kent
    University of Tokyo, Japan .
    Yao, Atsushi
    University of Tokyo, Japan .
    Takazawa, Yutaka
    University of Tokyo, Japan .
    Ono, Minoru
    University of Tokyo, Japan .
    Kyo, Shunei
    University of Tokyo, Japan .
    Komuro, Issei
    University of Tokyo, Japan .
    Successful treatment of hemodynamic compromise caused by antibody-mediated and cellular rejection in a recipient 12 years after heart transplantation2013In: International Heart Journal, ISSN 1349-2365, E-ISSN 1349-3299, Vol. 54, no 5, p. 328-331Article in journal (Refereed)
    Abstract [en]

    Heart transplantation (HTx) is an established therapy for stage D heart failure due to recent advances in immunosuppressive regimens. However, antibody-mediated rejection remains an unsolved problem because of its refractoriness to standard immunosuppressive therapy with high mortality and graft loss. We experienced a 16-year old patient with hemodynamic compromise caused by both cellular and antibody-mediated rejection 12 years after HTx. The rejection was refractory to repeated steroid pulse treatment, intravenous immunoglobulin administration, and intensifying immunosuppression including addition of everolimus. Eventually, she was successfully treated with repeated plasma exchange accompanied by a single administration of the anti-CD20 monoclonal antibody rituximab.

  • 2.
    Imamura, Teruhiko
    et al.
    University of Tokyo, Japan .
    Kinugawa, Koichiro
    University of Tokyo, Japan .
    Kato, Naoko
    University of Tokyo, Japan .
    Minatsuki, Shun
    University of Tokyo, Japan .
    Muraoka, Hironori
    University of Tokyo, Japan .
    Inaba, Toshiro
    University of Tokyo, Japan .
    Maki, Hisataka
    University of Tokyo, Japan .
    Shiga, Taro
    University of Tokyo, Japan .
    Hatano, Masaru
    University of Tokyo, Japan .
    Hosoya, Yumiko
    University of Tokyo, Japan .
    Takahashi, Masao
    University of Tokyo, Japan .
    Yao, Atsushi
    University of Tokyo, Japan .
    Kyo, Shunei
    University of Tokyo, Japan .
    Ono, Minoru
    University of Tokyo, Japan .
    Komuro, Issei
    University of Tokyo, Japan .
    A case with recovery of response to tolvaptan associated with remission of acute kidney injury and increased urine osmolality2013In: International Heart Journal, ISSN 1349-2365, E-ISSN 1349-3299, Vol. 54, no 2, p. 115-118Article in journal (Refereed)
    Abstract [en]

    Tolvaptan (TLV), a vasopressin type 2 receptor antagonist, has been demonstrated to be effective in patients with decompensated heart failure (HF) refractory to incremental doses of diuretics, but the responsiveness has not always been predictable. We have recently proposed that urine osmolality (U-OSM) is a valuable parameter for the prediction of responses to TLV, because U-OSM reflects the activity of the collecting ducts, where TLV plays its unique role. Acute kidney injury (AKI) is often associated with severe tubular dysfunction, including the collecting ducts, and in such cases a response to TLV may not be expected. We here experienced a patient with HF and AKI in whom TLV was not effective during AKI. We also observed recovery of responsiveness to TLV along with remission of AKI as well as increased U-OSM later on. We believe that this is the first report on the reversibility of the TLV response in relation to U-OSM.

  • 3.
    Imamura, Teruhiko
    et al.
    University of Tokyo, Japan .
    Kinugawa, Koichiro
    University of Tokyo, Japan .
    Kato, Naoko
    University of Tokyo, Japan .
    Minatsuki, Shun
    University of Tokyo, Japan .
    Muraoka, Hironori
    University of Tokyo, Japan .
    Inaba, Toshiro
    University of Tokyo, Japan .
    Maki, Hisataka
    University of Tokyo, Japan .
    Shiga, Taro
    University of Tokyo, Japan .
    Hatano, Masaru
    University of Tokyo, Japan .
    Yao, Atsushi
    University of Tokyo, Japan .
    Kyo, Shunei
    University of Tokyo, Japan .
    Ono, Minoru
    University of Tokyo, Japan .
    Komuro, Issei
    University of Tokyo, Japan .
    Successful Conversion From Thiazide to Tolvaptan in a Patient With Stage D Heart Failure and Chronic Kidney Disease Before Heart Transplantation2013In: International Heart Journal, ISSN 1349-2365, E-ISSN 1349-3299, Vol. 54, no 1, p. 48-50Article in journal (Refereed)
    Abstract [en]

    Chronic kidney disease (CKD) is often complicated with advanced heart failure because of not only renal congestion and decreased renal perfusion but also prolonged use of diuretics at higher doses, which sometimes results in hyponatremia. Preoperative CKD is known to be associated with poor prognosis after heart transplantation (HTx). We experienced a stage D heart failure patient with CKD and hyponatremia who was switched from trichlormethiazide to tolvaptan. His hyponatremia was normalized, and his renal function was improved after conversion to tolvaptan. In patients with stage D heart failure, it may be useful to administer tolvaptan with a concomitant reduction in the dose of diuretics in order to preserve renal function and avoid hyponatremia before HTx.

  • 4.
    Imamura, Teruhiko
    et al.
    University of Tokyo, Japan .
    Kinugawa, Koichiro
    University of Tokyo, Japan .
    Minatsuki, Shun
    University of Tokyo, Japan .
    Muraoka, Hironori
    University of Tokyo, Japan .
    Kato, Naoko
    University of Tokyo, Japan .
    Inaba, Toshiro
    University of Tokyo, Japan .
    Maki, Hisataka
    University of Tokyo, Japan .
    Hatano, Masaru
    University of Tokyo, Japan .
    Yao, Atsushi
    University of Tokyo, Japan .
    Komuro, Issei
    University of Tokyo, Japan .
    Tolvaptan Can Improve Clinical Course in Responders Validation Analysis for the Definition of Responsiveness by Urine Volume2013In: International Heart Journal, ISSN 1349-2365, E-ISSN 1349-3299, Vol. 54, no 6, p. 377-381Article in journal (Refereed)
    Abstract [en]

    We previously defined "responders" as patients with increases in urine volume (UV) on day 1 after the administration of tolvaptan (TLV), and demonstrated that responders to TLV could be predicted with considerable accuracy by urine osmolality (U-OSM) levels. Responders and non-responders to TLV should be associated with different clinical courses after a certain time following TLV administration. Therefore, the aim of the present study was to validate our definition of responders by clinical parameters 1 week after administration of TLV. Data (n = 85) were obtained from in-hospital patients with decompensated heart failure (HF) who had received TLV at 3.75-15 mg daily, and clinical data at 1 week after the administration of Thy were compared with those of baseline. Sixty patients (70.6%) were "responders", in whom UV on day 1 increased after the administration of TLV compared with day 0. "Non-responders" were older, and had higher serum creatinine concentration and lower baseline U-OSM than "responders". Serum creatinine concentration increased significantly in "non-responders", but was unchanged in "responders". Body weight, plasma B-type natriuretic peptide concentration, and HF symptom score decreased significantly in "responders", but remained unchanged in "non-responders". Increases in UV after the first administration of TLV were closely correlated with improvement of congestive HF after 1 week of TLV treatment, which verified our definition of "responders" to TLV.

  • 5.
    Imamura, Teruhiko
    et al.
    University of Tokyo, Japan .
    Kinugawa, Koichiro
    University of Tokyo, Japan .
    Minatsuki, Shun
    University of Tokyo, Japan .
    Muraoka, Hironori
    University of Tokyo, Japan .
    Kato, Naoko
    University of Tokyo, Japan .
    Inaba, Toshiro
    University of Tokyo, Japan .
    Maki, Hisataka
    University of Tokyo, Japan .
    Hatano, Masaru
    University of Tokyo, Japan .
    Yao, Atsushi
    University of Tokyo, Japan .
    Komuro, Issei
    University of Tokyo, Japan .
    Urine sodium excretion after tolvaptan administration is dependent upon baseline serum sodium levels: a possible explanation for the improvement of hyponatremia with scarce chance of hypernatremia by a vasopressin receptor antagonist2014In: International Heart Journal, ISSN 1349-2365, E-ISSN 1349-3299, Vol. 55, no 2, p. 131-137Article in journal (Refereed)
    Abstract [en]

    Several studies have demonstrated that tolvaptan (TLV) can improve hyponatremia in advanced heart failure (BF) patients with rare chance of hypernatremia. However, changes in serum sodium concentrations (S-Na) in patients with or without hyponatremia during TLV treatment have not been analyzed. Ninety-seven in-hospital patients with decompensated HF who had received TLV at 3.75-15 mg/day for 1 week were enrolled. Among 68 "responders", who had achieved any increases in urine volume (UV) during the first day, urinary sodium excretion during 24 hours (U-NaEx(24)) increased significantly during one week of TLV treatment along with higher baseline S-Na (P less than 0.05 and r = 0.325). Considering a cut-off value (S-Na, 132 mEq/L; AUC, 0.711) for any increases in U-NaEx(24), we defined "hyponatremia" as S-Na less than 132 mEq/L. In hyponatremic responders (n = 25), S-Na increased significantly, although 1 week was not sufficient for normalization (125.8 +/- 5.0 versus 128.9 +/- 4.3 mEq/L, P less than 0.05), along with unchanged U-NaEx(24) (2767 +/- 2703 versus 2972 +/- 2950 mg/day, NS). In contrast, in normonatremic responders (n = 43), S-Na remained unchanged (136.6 +/- 3.1 versus 137.4 +/- 2.9 mEq/L, NS) along with increased U-NaEx(24) (2201 +/- 1644 versus 4198 +/- 3550 mg/day, P less than 0.05). TLV increased S-Na only in hyponatemic responders by way of pure aquaresis, but increased U-NaEx(24) only in nonnonatremic responders, which explains the scarcity of hypernatremia. Epithelial Na-channels in the distal nephrons, whose repression by TLV increases urinary sodium excretion, may be attenuated by reduced ATP-supply in worse hemodynamics under hyponatremia.

  • 6.
    Imamura, Teruhiko
    et al.
    University of Tokyo, Japan .
    Kinugawa, Koichiro
    University of Tokyo, Japan .
    Ono, Minoru
    University of Tokyo, Japan .
    Kagami, Yukie
    University of Tokyo, Japan .
    Endo, Miyoko
    University of Tokyo, Japan .
    Minatsuki, Shun
    University of Tokyo, Japan .
    Muraoka, Hironori
    University of Tokyo, Japan .
    Kato, Naoko
    University of Tokyo, Japan .
    Inaba, Toshiro
    University of Tokyo, Japan .
    Maki, Hisataka
    University of Tokyo, Japan .
    Hatano, Masaru
    University of Tokyo, Japan .
    Yao, Atsushi
    University of Tokyo, Japan .
    Kyo, Shunei
    University of Tokyo, Japan .
    Komuro, Issei
    University of Tokyo, Japan .
    Everolimus-incorporated immunosuppressant strategy improves renal dysfunction while maintaining low rejection rates after heart transplantation in Japanese patients2013In: International Heart Journal, ISSN 1349-2365, E-ISSN 1349-3299, Vol. 54, no 4, p. 222-227Article in journal (Refereed)
    Abstract [en]

    The long-term survival of heart transplantation (HTx) recipients has increased significantly in recent years, however, the nephrotoxic adverse effects of calcineurin inhibitors (CNIs) are still a major concern. Recently, an inhibitor of mammalian target of rapamycin, everolimus (EVL), has emerged as an alternative immunosuppressant drug that may allow CM dosage reduction and thereby spare renal function. Data were collected from 20 HTx recipients who had received EVL (target trough level 3-8 ng/mL) along with a dose reduction of CNIs and/or mycophenolate mophetil (MMF) and had been followed for 1 year. Estimated glomerular filtration rate increased significantly with a reduction in the CM dosage in a dose-dependent manner (P less than 0.001, r = -0.807). Neutrophil count increased significantly (P less than 0.05) with a reduction in the dosage of MMF (P = 0.009, r = -0.671). Cytomegalovirus antigenemia remained negative after EVL administration among all candidates without any antiviral agents (P = 0.001). There were no significant increases in the acute rejection rates among recipients with EVL compared to those without EVL (P = 0.132). An immunosuppressant strategy incorporating EVL could reduce the CM and MMF dosages, which resulted in improvements in renal dysfunction and neutropenia while maintaining low rejection rates among HTx recipients.

  • 7.
    Imamura, Teruhiko
    et al.
    University of Tokyo, Japan .
    Kinugawa, Koichiro
    University of Tokyo, Japan .
    Shiga, Taro
    University of Tokyo, Japan .
    Kato, Naoko
    University of Tokyo, Japan .
    Endo, Miyoko
    University of Tokyo, Japan .
    Inaba, Toshiro
    University of Tokyo, Japan .
    Maki, Hisataka
    University of Tokyo, Japan .
    Hatano, Masaru
    University of Tokyo, Japan .
    Yao, Atsushi
    University of Tokyo, Japan .
    Hirata, Yasunobu
    University of Tokyo, Japan .
    Nishimura, Takashi
    University of Tokyo, Japan .
    Kyo, Shunei
    University of Tokyo, Japan .
    Ono, Minoru
    University of Tokyo, Japan .
    Nagai, Ryozo
    Jichi Medical University, Japan .
    Correction of hyponatremia by tolvaptan before left ventricular assist device implantation2012In: International Heart Journal, ISSN 1349-2365, E-ISSN 1349-3299, Vol. 53, no 6, p. 391-393Article in journal (Refereed)
    Abstract [en]

    Hypervolemic hyponatremia is often complicated with advanced heart failure together with increased excretion of sodium by diuretics. Tolvaptan, an oral vasopressin-2-receptor antagonist, has been previously reported to improve congestion and correct hyponatremia through increased excretion of free water. However, there is little evidence concerning the administration of tolvaptan in patients with stage D heart failure. We experienced 2 patients with stage D heart failure who received 3.75 mg/day of tolvaptan to correct hyponatremia before ventricular assist device implantation. It may be useful, even for patients with stage D heart failure, to administer a low dose of tolvaptan to treat hyponatremia before ventricular assist device implantation to avoid a drastic alteration in serum sodium concentration perioperatively.

  • 8.
    Imamura, Teruhiko
    et al.
    University of Tokyo, Japan .
    Shiga, Taro
    University of Tokyo, Japan .
    Kinugawa, Koichiro
    University of Tokyo, Japan .
    Kato, Naoko
    University of Tokyo, Japan .
    Endo, Miyoko
    Tokyo University Hospital, Japan .
    Inaba, Toshiro
    University of Tokyo, Japan .
    Maki, Hisataka
    University of Tokyo, Japan .
    Hatano, Masaru
    University of Tokyo, Japan .
    Yao, Atsushi
    University of Tokyo, Japan .
    Hirata, Yasunobu
    University of Tokyo, Japan .
    Nagai, Ryozo
    University of Tokyo, Japan .
    Successful conversion to everolimus after cytomegalovirus infection in a heart transplant recipient2012In: International Heart Journal, ISSN 1349-2365, E-ISSN 1349-3299, Vol. 53, no 3, p. 199-201Article in journal (Refereed)
    Abstract [en]

    Cytomegalovirus (CMV) infection remains a major problem in recipients with heart transplantation (HTx), because it may play a significant role in the development of cardiac allograft vasculopathy, which is one of the major causes of death after HTx. Valganciclovir (VGC) is effective for the treatment of CM V infection, but is often associated with neutropenia, especially when used with mycophenolate mophetil (MMF). We experienced an HTx recipient with positive CMV antigenemia who suffered progressive neutropenia after administration of VGC. We switched MMF to everolimus (EVL) and assay for CM V antigenemia was constantly negative even after discontinuation of VGC. In all other 14 HTx recipients who received EVL for any reason, we found that assay for CMV antigenemia remained negative throughout the period of EVL administration. Considering the prophylactic effect on CMV, EVL can not only be an alternative to rescue from comorbidity, but might also be indicated earlier especially in CMV-seronegative HTx recipients. 

  • 9.
    Kato, Naoko
    et al.
    University of Tokyo, Japan .
    Kinugawa, Koichiro
    University of Tokyo, Japan .
    Nakayama, Etsuko
    Sakakibara Heart Institute, Japan .
    Hatakeyama, Akiko
    Sakakibara Heart Institute, Japan .
    Tsuji, Takako
    Sakakibara Heart Institute, Japan .
    Kumagai, Yumiko
    Sakakibara Heart Institute, Japan .
    Komuro, Issei
    University of Tokyo, Japan .
    Nagai, Ryozo
    Jichii Medical University, Japan .
    Development and psychometric properties of the Japanese heart failure knowledge scale2013In: International Heart Journal, ISSN 1349-2365, E-ISSN 1349-3299, Vol. 54, no 4, p. 228-233Article in journal (Refereed)
    Abstract [en]

    Knowledge about their own condition is important for patients with heart failure (HF). No valid, reliable, and easily administered instrument is available to measure this knowledge in clinical practice. In this study, a HF knowledge scale was developed, and its psychometric properties were tested. Items related to knowledge about HF were extracted from relevant guidelines. Content validity of the items was confirmed by an expert panel including a cardiologist and nurses specialized in treatment and care of patients with HF. A self-administered questionnaire was then distributed to 187 patients with BY (64.0 +/- 12.1 years, males 69%). In 62% patients, a left ventricular ejection fraction of less than 50% was identified. Exploratory factor analysis demonstrated the one-dimensionality of the 15-item HF knowledge scale. Mean score was 10.7 +/- 3.0 (range, 0-15). Known-group validity testing revealed a significant difference in HF knowledge score between patients newly diagnosed with HF and patients experienced with HF (9.4 +/- 3.2 versus 10.8 +/- 2.9, P = 0.043). In addition, HF knowledge scale scores were correlated with HF self-care scores assessed by the European Heart Failure Self-Care Behavior Scale for evaluation of criterion validity (rho = 0.304, P less than 0.001). Cronbachs alpha was 0.79, and item-total correlation was 0.22-0.51, thereby suggesting that the reliability of the scale was acceptable. Acceptable validity and reliability were demonstrated for the HF knowledge scale developed in this study. This instrument could be useful in evaluation of patient knowledge about HF.

  • 10.
    Kato, Naoko
    et al.
    University of Tokyo, Japan .
    Kinugawa, Koichiro
    University of Tokyo, Japan .
    Nakayama, Etsuko
    Sakakibara Heart Institute, Japan .
    Tsuji, Takako
    Sakakibara Heart Institute, Japan .
    Kumagai, Yumiko
    Sakakibara Heart Institute, Japan .
    Imamura, Teruhiko
    University of Tokyo, Japan .
    Maki, Hisataka
    University of Tokyo, Japan .
    Shiga, Taro
    University of Tokyo, Japan .
    Hatano, Masaru
    University of Tokyo, Japan .
    Yao, Atsushi
    University of Tokyo, Japan .
    Miura, Chikako
    Sakakibara Heart Institute, Japan .
    Komuro, Issei
    University of Tokyo, Japan .
    Nagai, Ryozo
    Jichi Medical University, Japan .
    Insufficient Self-Care Is an Independent Risk Factor for Adverse Clinical Outcomes in Japanese Patients With Heart Failure2013In: International Heart Journal, ISSN 1349-2365, E-ISSN 1349-3299, Vol. 54, no 6, p. 382-389Article in journal (Refereed)
    Abstract [en]

    Self-care is a cornerstone for the successful management of heart failure (UP). The purpose of this study was to examine the impacts of HF self-care on prognosis in Japanese patients with HF. A total of 283 HF outpatients (age 64 14, 70% male, 52% HFrEF) were enrolled. We asked patients to answer about their adhevence to 5 self-care behaviors (medication, eating a low-sodium diet, regular exercise, daily weight check, and treatment seeking behavior). On the basis of the results, we classified patients into a good self-care group and a poor self-care group. The primary outcome was HF hospitalization and/or cardiac death. In total, 65% of patients were classified into the poor self-care group. During a median follow-up of 2 years, cardiac events occurred more frequently in the poor self-care group (22% versus 9.6%, P = 0.013). Poor self-care was an independent risk factor for cardiac events in Cox regression analysis adjusted for clinical parameters (hazard ratio = 2.86, P = 0.005). Poor self-care was also associated with an increased number of HF hospitalizations as well as an extended length of hospital stay for HF. Poor knowledge about HF was an independent determinant for poor self-care in multivariate logistic regression analysis (odds ratio = 0.92, P = 0.019). Insufficient self-care is an independent risk factor for cardiac events in Japanese patients with HF.

  • 11.
    Nitta, Daisuke
    et al.
    University of Tokyo, Japan.
    Kinugawa, Koichiro
    Toyama University, Japan.
    Imamura, Teruhiko
    University of Tokyo, Japan.
    Perkiö Kato, Naoko
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. University of Tokyo, Japan.
    Komuro, Issei
    University of Tokyo, Japan.
    High Dose beta-Blocker Therapy Triggers Additional Reverse Remodeling in Patients With Idiopathic Non-Ischemic Cardiomyopathy A Lesson From a Preliminary Trial Including the Significance of Left Ventricular Diameter and BNP Change for Reverse Remodeling2016In: International Heart Journal, ISSN 1349-2365, E-ISSN 1349-3299, Vol. 57, no 6, p. 717-724Article in journal (Refereed)
    Abstract [en]

    Carvedilol has established its evidence to improve prognosis and facilitate left ventricular reverse remodeling (LVRR) in heart failure patients with reduced left ventricular ejection fraction (LVEF), and many studies have supported its dose-dependency. However, there are few studies demonstrating the effect of high dose carvedilol in Japan. We enrolled 23 patients with idiopathic non-ischemic cardiomyopathy, in whom LVEF remained 45% or less despite 20 mg/ day of carvedilol therapy for amp;gt; 3 months. After high dose (40 mg/day) carvedilol therapy for amp;gt; 3 months, LVEF improved (+9.1%, P = 0.002), and LV end-diastolic diameter (LVDd) and LV end-systolic diameter (LVDs) reduced (-4.6 and -6.9 mm, respectively, P amp;lt; 0.05) compared with the baseline data. Finally, 17 patients achieved LVRR after the high dose, when LVRR was defined as 1) those with final EF amp;gt; 45%, and 2) those with final EF amp;lt; 45% but who attained increases in LVEF amp;gt; 10%, or LVEF amp;gt; 5% with a decrease in LV end-diastolic dimension index (LVDDI) amp;gt; 5%. Baseline predictors for LVRR after high dose carvedilol were the change rates of log B-type natriuretic peptide (BNP), LVDd, and LVDs from the time of pre-carvedilol introduction to enrollment (P amp;lt; 0.05, respectively). In conclusion, high dose carvedilol triggered additional LVRR in patients with idiopathic non-ischemic cardiomyopathy and the change rates of log BNP, LVDd, and LVDs at 20 mg carvedilol may be predictors for the additional LVRR at high dose.

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