Publications by authors named "Makiko Nakamura"

58 Publications

Impact of the whole activated clotting time during Impella support on short-term prognosis.

J Artif Organs 2021 May 13. Epub 2021 May 13.

Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan.

Impella (Abiomed, Danvers, MA, USA) is a percutaneous trans-catheter left ventricular assist device. Anticoagulant therapy targeting whole activated clotting time (ACT) between 160 and 180 s is recommended to prevent pump thrombosis during support. However, we sometimes experience fatal bleeding despite achieving the target ACT range. Consecutive patients who received Impella support in our institute between March 2018 and October 2020 were included in this retrospective study. The association between the averaged ACT levels during the Impella support and 30-day mortality was investigated. A total of 36 patients (71 years old, 61% males) were included. Most of the patients were managed within the recommended therapeutic range of ACT, and the average ACT level was 162 s. The higher ACT group (> 168 s) had older age, smaller body mass index, and higher serum creatinine compared with the lower ACT group (p < 0.05 for all). A higher ACT level was an independent risk factor of 30-day mortality with an adjusted hazard ratio of 1.085 (95% confidence interval 1.037-1.154) with a cut-off level of 168 s. There were only two thromboembolic events. Patients managed with higher ACT levels had a higher risk of 30-day mortality during Impella support. A low-dose heparin purge solution might be recommended in patients with high-risk for bleeding events.
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http://dx.doi.org/10.1007/s10047-021-01271-7DOI Listing
May 2021

Impact of optimal heart rate on left ventricular reverse remodeling and functional improvement in patients with systolic heart failure.

Heart Vessels 2021 May 6. Epub 2021 May 6.

Second Department of Internal Medicine, University of Toyama, 2630 Sugitani Toyama, Toyama, 930-0194, Japan.

Heart rate modulation therapy using ivabradine reduces mortality and morbidity in patients with systolic heart failure, whereas too reduced heart rate seems to worsen the clinical outcome. The optimal heart rate during heart rate modulation therapy remains unknown. Consecutive patients with left ventricular ejection fraction < 50% who received echocardiographic assessments and simultaneous heart rate measurements were retrospectively investigated. Theoretically ideal heart rate was calculated using a previously proposed formula: 93 - 0.13 × (deceleration time [msec]). Impacts of heart rate on the 1-year echocardiographic left ventricular reverse remodeling were compared among the three groups stratified by the heart rate status: optimal heart rate group (within 10 bpm of ideal heart rate), below-optimal heart rate group (< 10 bpm of ideal heart rate), and above-optimal heart rate group (> 10 bpm of ideal heart rate). A total of 75 patients (70 years old, 60 men) were included. There were no significant differences in the baseline characteristics among the three groups, except for the higher prevalence of tolvaptan use and higher plasma B-type natriuretic peptide level in the below-optimal heart rate group. Left ventricular end-diastolic diameter (from 55 to 54) and left ventricular ejection fraction (from 39 to 46) improved significantly only in the optimal heart rate group at 1-year follow-up (p < 0.05 for both). Optimal heart rate, which was calculated using a formula consisting of deceleration time, was associated with cardiac reverse remodeling in patients with systolic heart failure. Prospective study to investigate the implication of deceleration time-guided aggressive heart rate optimization is the next concern.
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http://dx.doi.org/10.1007/s00380-021-01864-5DOI Listing
May 2021

Patisiran for advanced heart failure with hereditary transthyretin cardiac amyloidosis.

J Cardiol Cases 2021 Apr 8;23(4):177-180. Epub 2021 Feb 8.

The Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama 930-0194, Japan.

We experienced a 78-year-old woman who was diagnosed with hereditary transthyretin cardiac amyloidosis and administered patisiran for advanced heart failure refractory to tafamidis. The levels of N-terminal pro B-type natriuretic peptide and left ventricular mass index decreased following the six-month patisiran treatment without any complications. Patisiran might be a promising disease-modifying drug for hereditary transthyretin cardiac amyloidosis even in its advanced stage, although further evaluation in a large cohort is warranted.
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http://dx.doi.org/10.1016/j.jccase.2021.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020066PMC
April 2021

Therapeutic Strategy for a Patient with Advanced Heart Failure and Schizophrenia Without Cardiac Replacement Therapies.

Int Heart J 2021 Mar 17;62(2):441-444. Epub 2021 Mar 17.

Second Department of Internal Medicine, University of Toyama.

We had a 58-year-old man with advanced heart failure and progressive end-organ dysfunction refractory to inotropes. Following detailed discussions, he decided not to receive ventricular assist device therapy considering his comorbidity of schizophrenia. A palliative care team initiated 2.5 mg of morphine together with low-dose anti-heart failure medications, which improved not only his heart failure symptoms but also the congestive heart failure itself. Aggressive commitments of the palliative care team might improve not only patients' quality of life but also advanced heart failure itself.
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http://dx.doi.org/10.1536/ihj.20-624DOI Listing
March 2021

Initial Experience With Tafamidis Treatment for Transthyretin Amyloid Cardiomyopathy.

Circ Rep 2020 Jul 21;2(8):420-424. Epub 2020 Jul 21.

Second Department of Internal Medicine, University of Toyama Toyoma Japan.

Transthyretin amyloid cardiomyopathy is a progressive disease with a poor prognosis. There had been no specific treatment for transthyretin amyloid cardiomyopathy until tafamidis received expanded approval in March 2019 in Japan. However, the clinical efficacy of tafamidis remains unknown. We initiated tafamidis treatment in 9 patients (median age 78 years; 89% male) from May 2019 to April 2020. Within 6 months after initiation, 1 patient discontinued prematurely and 2 patients were hospitalized due to worsening heart failure, with 1 of these patients discontinuing therapy. There were no significant changes in plasma B-type natriuretic peptide and serum troponin I concentrations over the 6-month treatment period, but interventricular septum thickness increased in 3 of 6 patients. Further evaluation of tafamidis therapy in a larger patient cohort with transthyretin amyloid cardiomyopathy is warranted to determine the optimal therapeutic strategy.
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http://dx.doi.org/10.1253/circrep.CR-20-0062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819654PMC
July 2020

Prognostic implication of risk scoring systems in patients with cardiogenic shock supported by ECMO and Impella.

J Artif Organs 2021 Jan 3. Epub 2021 Jan 3.

The Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan.

We experienced two refractory cardiogenic shock patients receiving veno-arterial extracorporeal membrane oxygenation and Impella percutaneous left ventricular assist device (ECPELLA). TVAD score, which was originally proposed to predict one-year mortality following left ventricular assist device implantation using four objective parameters, was retrospectively calculated using data of day 3 following ECPELLA initiations. One patient with estimated intermediate risk could achieve successful explantation of ECPELLA, whereas another patient with estimated high risk was expired despite explantation of extracorporeal membrane oxygenation. TVAD score might be a useful tool to risk stratify and construct next strategy (i.e., bridge to recovery or bridge to more intensive therapy) for those with ECPELLA, although further studies are warranted to validate this hypothesis.
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http://dx.doi.org/10.1007/s10047-020-01232-6DOI Listing
January 2021

A case of wild-type transthyretin cardiac amyloidosis with rheumatoid arthritis.

Mod Rheumatol Case Rep 2021 Jan 18:1-9. Epub 2021 Jan 18.

First Department of Internal Medicine, University of Toyama, Toyama, Japan.

A 72-year-old woman was diagnosed with rheumatoid arthritis (RA) 6 years ago and was referred to our hospital for the management of RA. She achieved remission with methotrexate, and her arthritis was well-controlled. Two years ago, a routine, preoperative check-up revealed left ventricular hypertrophy. One month before the current admission, she experienced worsening heart failure, and echocardiography and other findings suggested cardiac amyloidosis as the underlying cause. She was then admitted to our hospital. Biopsies of both the myocardium and duodenum showed amyloid deposits, and the initial immunohistochemical examination suggested amyloid A (AA) amyloidosis, as the deposits were slightly positive to anti-AA antibody and were sensitive to potassium permanganate pre-treatment. Thus, cardiac and duodenal AA amyloidosis secondary to RA was considered. However, the patient had no renal lesions and her RA was strictly controlled, findings atypical of AA amyloidosis. On repeat immunohistochemical testing, the cardiac and duodenal samples were negative for AA but stained positive for transthyretin (TTR). The diagnosis of a wild-type TTR amyloidosis (ATTRwt) was confirmed on the basis of an absence of the TTR gene mutation. The patient was successfully treated with diuretics and enalapril, and tafamidis (potent and selective TTR stabiliser). A pacemaker was implanted for concomitant complete atrioventricular block. This case is the first reported case of systemic ATTRwt complicated by RA. The treatment strategy for amyloidosis differs greatly depending on the type of amyloid deposition. Therefore, it is important to properly identify the amyloid protein, even if the diagnosis is complicated by RA.
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http://dx.doi.org/10.1080/24725625.2020.1864104DOI Listing
January 2021

Usefulness of HVAD Waveforms as Diagnostic Assistance for Cardiac Tamponade.

ASAIO J 2021 04;67(4):e90-e92

From the The Second Department of Internal Medicine, University of Toyama, Toyama, Japan.

We experienced a 39-year-old male patient who converted paracorporeal left ventricular assist device to HeartWare ventricular assist device (HVAD; Medtronic, Framingham, MA) as bridge-to-transplant indication. On the 10th postoperative day, the HVAD flow waveform presented periodical low pulsatility pattern. Significant pericardial hematoma was observed on the imaging studies, and he showed pulsus paradoxus. He was highly suspected of cardiac tamponade and performed thoracotomy. HVAD waveform might be a useful tool to monitor and early suspect of postoperative cardiac tamponade to consider more intensive examinations and thoracotomy before hemodynamic deterioration, although further large-scale studies are warranted to strengthen our hypothesis.
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http://dx.doi.org/10.1097/MAT.0000000000001303DOI Listing
April 2021

Practical Management of ECPELLA.

Int Heart J 2020 Nov 28;61(6):1094-1096. Epub 2020 Oct 28.

Second Department of Internal Medicine, University of Toyama.

Veno-arterial extracorporeal membrane oxygenation (ECMO) is a strong mechanical circulatory device for patients with hemodynamic deterioration due to cardiogenic shock, but its drawback is an increase in left ventricular afterload. The Impella axial-flow transcatheter left ventricular assist device is a recently developed promising device to mechanically unload the left ventricle, although its support flow may not necessarily be sufficient to support shock vital. Recently, ECMO and concomitant Impella support (ECPELLA) is increasingly being used to treat cardiogenic shock by maintaining systemic circulation and unloading the left ventricle. There are several pitfalls to maintaining ECPELLA, and one useful tool is the pulmonary artery pulsatility index. The clinical advantages of ECPELLA compared to conventional ECMO alone should be demonstrated in larger scale studies in the near future.
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http://dx.doi.org/10.1536/ihj.20-172DOI Listing
November 2020

Implication of Ivabradine in Up-titrating Beta-blocker in a Patient with Advanced Heart Failure.

Intern Med 2021 Mar 21;60(6):897-900. Epub 2020 Oct 21.

The Second Department of Internal Medicine, University of Toyama, Japan.

Titration of beta-blockers is a gold-standard therapy in patients with heart failure and a reduced ejection fraction but is sometimes challenging to administer, given symptomatic hypotension. Ivabradine is a recently introduced selective I channel inhibitor that purely reduces the heart rate. We encountered a patient with advanced heart failure in whom a beta-blocker could not be up-titrated given his symptomatic hypotension. Following the initiation of ivabradine, an increase in blood pressure due to heart rate optimization, probably via an improvement in the cardiac output, allowed for the further up-titration of carvedilol, followed by a successful clinical course. Ivabradine might be a novel therapeutic tool to facilitate the up-titration of beta-blockers in patients with heart failure and hypotension.
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http://dx.doi.org/10.2169/internalmedicine.6061-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024963PMC
March 2021

Regulation of Angiopoietin-2 Before and After Mechanical Circulatory Support Therapy.

ASAIO J 2021 01;67(1):53-58

From the Second Department of Internal Medicine; and.

Gastrointestinal bleeding (GIB) during mechanical circulatory support (MCS) is a major unsolved comorbidity. Inadequate activation of angiopoietin-2-related systems is considered as a major cause of GIB. However, the regulation of angiopoietin-2 remains unknown. Consecutive 20 patients who received continuous-flow MCS therapy (MCS group) and 12 with advanced heart failure (HF; HF group) were prospectively enrolled and their angiopoetin-2 levels were compared. Angiopoietin-2 level had a moderate correlation with log10 B-type natriuretic peptide (BNP; r = 0.39, p < 0.001). The MCS group had significantly higher angiopoietin-2 level divided by log10 BNP compared with the HF group (2.80 ± 0.20 vs. 1.88 ± 0.17, p < 0.001). Angiopoetin-2 had a moderate correlation with central venous pressure and C-reactive protein during the MCS support (r = 0.51 and r = 0.45, respectively). Higher angiopoietin-2 level divided by log10 BNP (> 4.3) was significantly associated with the occurrence of GIB with a hazard ratio of 296 (95% confidence interval 2.24-38620, p = 0.0224). Angiopoietin-2 was already elevated in the HF cohort and more elevated following MCS initiation. Among the MCS cohort, angiopoietin-2 was particularly elevated in patients with systemic congestion and inflammation and was associated with higher incidence of GIB.
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http://dx.doi.org/10.1097/MAT.0000000000001189DOI Listing
January 2021

Implication of Impella 5.0 therapy as a bridge tool from VA-ECMO to durable LVAD therapy.

J Crit Care 2020 12 15;60:347. Epub 2020 Jul 15.

Second Department of Medicine, University of Toyama, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.jcrc.2020.06.010DOI Listing
December 2020

How to consider target heart rate in patients with systolic heart failure.

ESC Heart Fail 2020 10 27;7(5):3231-3234. Epub 2020 Jun 27.

Second Department of Medicine, University of Toyama, 2630 Sugitani Toyama, Toyama, 930-0194, Japan.

Aims: Heart rate reduction therapy using ivabradine, a selective inhibitor of the funny current of the sinoatrial node, is widely used in the systolic heart failure cohort. However, the optimal target of heart rate remains controversial. The association between heart rate and 'overlap' between E-wave and A-wave in the pulse wave transmitral flow Doppler echocardiography might be a key to find the ideal heart rate in each individual.

Methods And Results: We performed transthoracic echocardiography in patients with systolic heart failure, and the association between heart rate, deceleration time, and overlap length between E-wave and A-wave was assessed. In total, 368 patients with systolic heart failure (median 76 years old, 190 men, median ejection fraction 40%) were included. The measured overlap length was 35 (-72, 115) ms. Given the results of multiple linear regression analyses, we constructed a formula: estimated overlap length (ms) = -589 + 6.2 × heart rate (bpm) + 0.81 × deceleration time (ms), which had a good agreement with actually measured one (r = 0.62). The ideal heart rate, at which the overlap length is 'zero' and probably cardiac output is maximized, is calculated as follows: ideal heart rate (bpm) = 93 - 0.13 × deceleration time (ms).

Conclusions: We proposed a novel formula using deceleration time to estimate ideal heart rate that achieves a zero overlap between E-wave and A-wave in patients with systolic heart failure. Prognostic impact of the formula-guided heart rate optimization should be studied.
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http://dx.doi.org/10.1002/ehf2.12814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524252PMC
October 2020

Paracorporeal Ventricular Assist Device Implantation in a Patient with Transposition of the Great Arteries After Senning Operation.

Int Heart J 2020 May 15;61(3):616-619. Epub 2020 May 15.

Second Department of Internal Medicine, University of Toyama.

We experienced a 33-year-old patient with D-looped transposition of the great arteries (D-TGA) and a history of Senning operation who was referred to our institute with cardiogenic shock and subsequently underwent urgent paracorporeal ventricular assist device (VAD) implantation, which was a first in Japan, that was eventually converted to a durable VAD. Central venous pressure was maintained relatively high to obtain VAD filling and recover end-organ dysfunction, given the migration of the inflow cannula due to rich trabeculae carneae of the anatomical right ventricle (systemic ventricle in this case).
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http://dx.doi.org/10.1536/ihj.19-670DOI Listing
May 2020

Impact of the angle between aortic and mitral annulus on the occurrence of hemolysis during Impella support.

J Artif Organs 2020 Sep 14;23(3):207-213. Epub 2020 May 14.

Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama, 930-0194, Japan.

Despite optimal management, we sometimes experience refractory hemolysis requiring extensive device speed reduction or continuous hemodiafiltration following Impella implantation. However, pre-procedural predictors of such a refractory hemolysis remain unknown. In this study, we investigated the pre-procedural factors, including the echocardiographic narrow angle between aortic and mitral annulus, associating with the occurrence of refractory hemolysis following Impella insertion. We enrolled 26 patients (71 years, 65% male) who received Impella insertion between March 2018 and November 2019. Among baseline characteristics, the angle between aortic and mitral annulus, < 126.5°, was an independent risk factor of refractory hemolysis with an adjusted hazard ratio of 7.840 (95% confidence interval 0.925-66.44) and was associated with lower 30-day survival (64% vs. 100%, p = 0.0116). The narrow angle between aortic and mitral annulus might be a useful tool to risk-stratify the occurrence of refractory hemolysis following Impella insertion.
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http://dx.doi.org/10.1007/s10047-020-01172-1DOI Listing
September 2020

Impella support as a bridge to scheduled surgical repair of ventricular septal rupture.

J Artif Organs 2020 Sep 27;23(3):278-282. Epub 2020 Mar 27.

The Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, Toyama, 930-0194, Japan.

We studied the experience of a 69-year-old woman with acute decompensated heart failure due to post-infarction ventricular septal rupture. She received mechanical hemodynamic support by Impella 2.5 (Abiomed, Danvers, MA, USA), percutaneous axial-flow left ventricular assist device, which improved intra-cardiac pressure, maintaining end-organ function. She was successfully bridged to the scheduled surgical repair of ventricular septal rupture following the 9-day Impella support and discharged on foot on the 32nd day. Impella might be a useful mechanical circulatory support device as a bridge tool to the scheduled surgical repair of ventricular septal rupture if used with careful daily management to prevent device-related comorbidities.
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http://dx.doi.org/10.1007/s10047-020-01163-2DOI Listing
September 2020

Current indication and practical management of percutaneous left ventricular assist device support therapy in Japan.

J Cardiol 2020 03 20;75(3):228-232. Epub 2019 Dec 20.

Second Department of Internal Medicine, University of Toyama, Toyama, Japan.

Impella (Abiomed, Danvers, MA, USA) is a recently-innovated (commercially available from 2017 in Japan) percutaneous left ventricular assist device which is inserted percutaneously and transfers blood from the left ventricle to the ascending aorta, improving systemic circulation and end-organ dysfunction as well as unloading left ventricle in patients with cardiogenic shock. Impella has not yet shown a significant survival benefit in patients with cardiogenic shock compared to intra-aortic balloon pump in randomized control trials, but gives powerful circulatory support immediately with minimally invasive manner when used in appropriate patients at optimal timing with adequate management. In this review article, we will introduce and discuss optimal and practical management of Impella therapy in Japan.
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http://dx.doi.org/10.1016/j.jjcc.2019.12.003DOI Listing
March 2020

Comparison of Canagliflozin, Dapagliflozin and Empagliflozin Added to Heart Failure Treatment in Decompensated Heart Failure Patients With Type 2 Diabetes Mellitus.

Circ Rep 2019 Sep 27;1(10):405-413. Epub 2019 Sep 27.

Second Department of Internal Medicine, University of Toyama Toyama Japan.

Three sodium-glucose cotransporter-2 inhibitors (SGLT2i), canagliflozin, dapagliflozin and empagliflozin, successfully reduced hospitalization for heart failure (HF) in patients with type 2 diabetes mellitus (T2DM). It remains unclear, however, whether the efficacy of the 3 SGLT2i for HF in T2DM patients is similar. Eighty-one T2DM patients hospitalized due to decompensated HF were enrolled. After treatment for HF, one of the 3 SGLT2i was non-randomly used, and clinical parameters for HF and T2DM were followed for 7 days. The attending physician was allowed to adjust the dose of furosemide. No differences were observed between the 3 groups in the increase of glycosuria, or in the decreases of body weight and blood pressure 7 days after SGLT2i (interaction P>0.05). Urine volume was similarly increased on day 1, and returned to the baseline on day 7 in each group. Decrease in B-type natriuretic peptide and increase in plasma renin activity were significant in each group. Plasma aldosterone concentration, however, was significantly increased in the empagliflozin and canagliflozin groups (P<0.01, respectively), but not in the dapagliflozin group. Additionally, plasma noradrenaline was significantly increased in the empagliflozin group (P<0.01), but not in the canagliflozin and dapagliflozin groups. The neurohumoral responses to the 3 SGLT2i are different under similar volume correction in HF patients with T2DM.
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http://dx.doi.org/10.1253/circrep.CR-19-0070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897568PMC
September 2019

First Experience of Transfer with Impella 5.0 Over the Long Distance in Japan.

Int Heart J 2019 Sep 4;60(5):1219-1221. Epub 2019 Sep 4.

Second Department of Internal Medicine, University of Toyama.

We recently experienced a 43-year-old man with dilated cardiomyopathy transported under the Impella support to a high-volume left ventricular assist device (LVAD) center. Stabilized hemodynamics with the Impella and firm fixation of the device were important for safe transportation of the patient.
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http://dx.doi.org/10.1536/ihj.19-038DOI Listing
September 2019

A case of Takotsubo cardiomyopathy with cardiogenic shock after influenza infection successfully recovered by IMPELLA support.

J Artif Organs 2019 Dec 21;22(4):330-333. Epub 2019 Jun 21.

Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.

We recently experienced a case of cardiogenic shock due to influenza-related Takotsubo cardiomyopathy with atrial tachycardia and respiratory distress syndrome. Temporary mechanical circulatory support by IMPELLA 2.5 improved end-organ failure and resulted in cardiac recovery with sinus rhythm conversion.
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http://dx.doi.org/10.1007/s10047-019-01112-8DOI Listing
December 2019

A case of cardiogenic shock due to acute coronary syndrome successfully recovered by percutaneous and paracorporeal left ventricular assist device.

J Artif Organs 2019 Sep 1;22(3):249-252. Epub 2019 Apr 1.

The Second Department of Internal Medicine, University of Toyama, 2630 Sugitani, Toyama-City, 930-0194, Japan.

We recently experienced a 70-year-old woman with left main trunk-acute coronary syndrome who was initially supported by Impella 5.0 which converted to paracorporeal left ventricular assist device (LVAD) implantation as a bridge to recovery. Optimized guideline-directed medical therapy with cardiac rehabilitation resulted in successful explantation of LVAD and she discharged on foot.
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http://dx.doi.org/10.1007/s10047-019-01101-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685920PMC
September 2019

Tolvaptan Improves Prognosis in Responders with Acute Decompensated Heart Failure by Reducing the Dose of Loop Diuretics.

Int Heart J 2018 ;59(1):87-93

Second Department of Internal Medicine, University of Toyama.

It is unknown whether a response to tolvaptan (TLV) is related to prognosis in patients with acute decompensated heart failure (ADHF). We selected 25 patients as responders by their urinary response to TLV and by reduction of loop diuretics from 37 consecutive ADHF patients treated with TLV. As a control group, we selected 25 patients from 100 consecutive ADHF patients who were not treated with TLV by propensity score matching for age, serum sodium level, serum creatinine level, plasma B-type natriuretic peptide (BNP) level, systolic blood pressure, heart rate, and dose of loop diuretics. The primary outcome was defined as a composite endpoint of mortality and/or hemodialysis. The amount of loop diuretics administered to responders was reduced by TLV from 68.8 ± 26.2 mg to 30.4 ± 18.6 mg of furosemide equivalents per day, whereas the loop diuretic dose administered to non-responders was increased. The event-free survival of the TLV responders during 20 months was significantly better than that of the control group (95.8% versus 68.4%, P = 0.0406). The TLV responders, plasma BNP level, and estimated glomerular filtration rate were significantly related to the events in the Cox proportional hazard analysis. Patients with ADHF who respond to TLV may have a better prognosis than propensity-matched patients not receiving TLV treatment. In TLV responders, it may be possible to improve the patient's prognosis if the dose of loop diuretics can be reduced with TLV therapy.
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http://dx.doi.org/10.1536/ihj.17-099DOI Listing
February 2018

Investigation of the transport of xanthine dehydrogenase inhibitors by the urate transporter ABCG2.

Drug Metab Pharmacokinet 2018 Feb 22;33(1):77-81. Epub 2017 Nov 22.

Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan. Electronic address:

Hyperuricemia induces gout and kidney stones and accelerates the progression of renal and cardiovascular diseases. Adenosine 5'-triphosphate-binding cassette subfamily G member 2 (ABCG2) is a urate transporter, and common dysfunctional variants of ABCG2, non-functional Q126X (rs72552713) and semi-functional Q141K (rs2231142), are risk factors for hyperuricemia and gout. A recent genome wide association study suggested that allopurinol, a serum uric acid-lowering drug that inhibits xanthine dehydrogenase, is a potent substrate of ABCG2. In this study, we aimed to examine the transport of xanthine dehydrogenase inhibitors via ABCG2. Our results show that ABCG2 transports oxypurinol, an active metabolite of allopurinol, whereas allopurinol and febuxostat, a new xanthine dehydrogenase inhibitor, are not substrates of ABCG2. The amount of oxypurinol transported by ABCG2 vesicles significantly increased in the presence of ATP, compared to that observed with mock vesicles. Since the half-life of oxypurinol is longer than that of allopurinol, the xanthine dehydrogenase-inhibiting effect of allopurinol mainly depends on its metabolite, oxypurinol. Our results indicate that the serum level of oxypurinol would increase in patients with ABCG2 dysfunction.
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http://dx.doi.org/10.1016/j.dmpk.2017.11.002DOI Listing
February 2018

Successful Withdrawal from Dobutamine by Canagliflozin in a Diabetic Patient with Stage D Heart Failure.

Int Heart J 2017 Dec 22;58(6):978-981. Epub 2017 Nov 22.

Second Department of Internal Medicine, University of Toyama.

Patients with stage D heart failure (HF) frequently become dependent on high doses of diuretics and inotropic agents. Recently, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), an oral antidiabetic agent, has been demonstrated to have favorable effects in preventing HF. However, it remains unknown whether SGLT2i is reliable for patients with decompensated HF. We experienced a case of a patient with stage D HF for whom attempting intravenous dobutamine withdrawal was difficult even after the administration of all conventional pharmacological treatment. Administration of canagliflozin produced an additive diuretic action and correction of volume overload in combination with azosemide and tolvaptan, and resulted in successful withdrawal of dobutamine. Thus, SGLT2i might be promising for the treatment of patients with congestive HF who are refractory to conventional diuretic treatment.
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http://dx.doi.org/10.1536/ihj.16-644DOI Listing
December 2017

Amiodarone-Induced Hyponatremia Masked by Tolvaptan in a Patient with an Implantable Left Ventricular Assist Device.

Int Heart J 2017 Dec 17;58(6):1004-1007. Epub 2017 Nov 17.

Second Department of Internal Medicine, University of Toyama.

A 43-year-old man was referred to our hospital in June 2014 because of severe heart failure. He was diagnosed with familial dilated cardiomyopathy and was administered oral tolvaptan and amiodarone for atrial and ventricular tachycardia. Since up-titration of carvedilol had failed and he was dependent on dobutamine, a left ventricular assist device (LVAD) was implanted. Tolvaptan and furosemide were both discontinued after LVAD implantation and he was discharged from the hospital. Thirteen months later, he was hospitalized for lethargy and hyponatremia of 108 mEq/L, with an antidiuretic hormone level of 2.5 pg/mL, which suggested syndrome of inappropriate antidiuretic hormone secretion (SIADH). We discontinued amiodarone and administered fludrocortisones. However, hyponatremia persisted for a few more days, eventually resulting in delirium and damage to the LVAD driveline. He received an urgent pump exchange and hyponatremia was gradually improved. We considered the possibility that amiodarone-induced SIADH was masked by tolvaptan therapy before LVAD implantation.
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http://dx.doi.org/10.1536/ihj.16-656DOI Listing
December 2017

A Case of Refractory Heart Failure in Becker Muscular Dystrophy Improved With Corticosteroid Therapy.

Int Heart J 2016 Sep 16;57(5):640-4. Epub 2016 Aug 16.

Department of Cardiology, Okinawa Prefectural Nanbu Medical Center and Children's Medical Center.

The patient was a 26 year-old man who was referred to our hospital in June 2011 because of severe heart failure. At age 24 years, he was found to have Becker muscular dystrophy. He received enalapril for cardiac dysfunction; however, he had worsening heart failure and was thus referred to our hospital. Echocardiography showed enlargement of the left ventricle, with a diastolic dimension of 77 mm and ejection fraction of 19%. His condition improved temporarily after an infusion of dobutamine and milrinone. He was then administered amiodarone for ventricular tachycardia; however, he subsequently developed hemoptysis. Amiodarone was discontinued and corticosteroid pulse therapy was administered followed by oral prednisolone (PSL). His creatinine phosphokinase (CPK) level and cardiomegaly improved after the corticosteroid therapy. The PSL dose was reduced gradually, bisoprolol was introduced, and the catecholamine infusion was tapered. A cardiac resynchronization device was implanted; however, the patient's condition gradually worsened, which necessitated dobutamine infusion for heart failure. We readministered 30 mg PSL, which decreased the CPK level and improved the cardiomegaly. The dobutamine infusion was discontinued, and the patient was discharged. He was given 7.5 mg PSL as an outpatient, and he returned to normal life without exacerbation of the heart failure. There are similar reports showing that corticosteroids are effective for skeletal muscle improvement in Duchenne muscular dystrophy; however, their effectiveness for heart failure has been rarely reported. We experienced a case of Becker muscular dystrophy in which corticosteroid therapy was effective for refractory heart failure.
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http://dx.doi.org/10.1536/ihj.16-044DOI Listing
September 2016

AN EPIZOOTIC OF EMERGING NOVEL AVIAN POX IN CARRION CROWS (CORVUS CORONE) AND LARGE-BILLED CROWS (CORVUS MACRORHYNCHOS) IN JAPAN.

J Wildl Dis 2016 04 11;52(2):230-41. Epub 2016 Mar 11.

8   Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo, Hokkaido 060-0818, Japan.

In 2006-10, an epizootic of emerging avian pox occurred in Carrion Crows ( Corvus corone ) and Large-billed Crows ( Corvus macrorhynchos ), leading to mortality of juvenile crows in Hokkaido, the northernmost island of Japan. We diagnosed 27 crows with proliferative skin lesions (19 carcasses and eight biopsied cases [one in zoo captivity]) as avian pox clinically, histopathologically by detection of Avipoxvirus-specific 4b core protein (P4b) gene, and epidemiologically. The fatal cases demonstrated intensively severe infection and aggressive lesions with secondary bacterial infection. Since the first identification of avian pox in Sapporo, Japan, in 2006, the frequency of mortality events has increased, peaking in 2007-08. Mortalities have subsequently occurred in other areas, suggesting disease expansion. In Sapporo, prevalence of avian pox evaluated by field censuses during 2007-12 was 17.6% (6.6-27.2%), peaked during 2007-08 and 2008-09, and then decreased. All diseased crows were juveniles, except for one adult. The number of crows assembling in the winter roosts had been stable for >10 yr; however, it declined in 2007-08, decreased by about 50% in 2008-09, and recovered to the previous level in 2009-10, correlated with the avian pox outbreak. Thus, avian pox probably contributed to the unusual crow population decline. All P4b sequences detected in six specimens in Sapporo were identical and different from any previously reported sequences. The sequence detected in the zoo-kept crow was distinct from any reported clades, and interspecies transmission was suspected. This report demonstrates an emerging novel avian pox in the Japanese avifauna and in global populations of Carrion Crows and Large-billed Crows. Longitudinal monitoring is needed to evaluate its impact on the crow population.
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http://dx.doi.org/10.7589/2015-07-172DOI Listing
April 2016

A case of percutaneous coronary intervention for treatment of iatrogenic chronic total occlusion of the left circumflex artery after mitral valve repair.

Cardiovasc Interv Ther 2017 Apr 5;32(2):146-150. Epub 2016 Feb 5.

Department of Cardiology, Okinawa Prefectural Nanbu Medical Center and Children's Medical Center, 118-1 Arakawa, Haebaru-cho, Okinawa, 901-1193, Japan.

A 55-year-old man had undergone mitral annuloplasty for mitral regurgitation with posterior mitral prolapse 3 years prior. He was examined at our hospital for dyspnea and fatigue. A coronary angiogram revealed iatrogenic chronic total occlusion (CTO) in the left circumflex coronary artery. We performed percutaneous coronary intervention (PCI) and successfully placed an everolimus-eluting stent. An intravascular ultrasound (IVUS) showed an impaired coronary artery at the occlusion site. To our knowledge, this is the first reported successful PCI for iatrogenic CTO after mitral valve repair. IVUS-guided PCI may help prevent complications in unusual CTO cases, such as coronary rupture.
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http://dx.doi.org/10.1007/s12928-016-0379-zDOI Listing
April 2017

Functional analysis of novel allelic variants in URAT1 and GLUT9 causing renal hypouricemia type 1 and 2.

Clin Exp Nephrol 2016 Aug 24;20(4):578-584. Epub 2015 Oct 24.

Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.

Background: Renal hypouricemia is a rare heterogeneous inherited disorder characterized by impaired tubular uric acid transport with severe complications, such as acute kidney injury and nephrolithiasis. Type 1 is caused by a loss-of-function mutation in the SLC22A12 gene (URAT1), while type 2 is caused by defects in the SLC2A9 gene (GLUT9).

Methods And Results: In this article we present clinical, biochemical and molecular genetics of two Czech patients. The serum uric acid in the probands was 57 and 98 µmol/l and expressed as an increase in the fractional excretion of uric acid (40 and 18 %). The sequencing analysis of SLC22A12 and SLC2A9 revealed novel variants p.R92C and p.R203C in URAT1 and p.G72D in GLUT9. Functional studies were performed for these novel variants and for previously reported variants p.I118HfsX27, p.G216R and p.N333S in GLUT9 responsible for renal hypouricemia in three probands from Czech Republic and United Kingdom. Functional studies showed significantly decreased urate uptake for all variants. However, urate uptake of GLUT9 variants prepared for both isoforms were not significantly different.

Conclusions: This is the first complex function characterization of non-synonymous allelic variants in patients with renal hypouricemia regarding both GLUT9 isoforms. Our finding of defects in the SLC2A9 and SLC22A12 genes show the following: renal hypouricemia is not restricted to East Asia populations; urate uptake of GLUT9 variants prepared for both isoforms were not significantly different; renal hypouricemia type 2 has more wide clinical variability than type 1; the phenotypic severity of renal hypouricemia is not correlated with results of functional characterizations of URAT1 and GLUT9 variants.
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http://dx.doi.org/10.1007/s10157-015-1186-zDOI Listing
August 2016