Publications by authors named "Makoto Hirai"

126 Publications

Increased afternoon step count increases heart rate variability in patients with cardiovascular risk factors.

J Clin Nurs 2021 Aug 29. Epub 2021 Aug 29.

Nagoya University Graduate School of Medicine, Nagoya, Japan.

Aims And Objectives: The present study investigated whether morning or afternoon activity is more effective at increasing the high-frequency (HF) index, a parasympathetic index, in patients with cardiovascular risk factors.

Background: A decreased HF index, a heart rate variability (HRV) parameter, is a well-established marker of poor cardiovascular prognosis. Because blood pressure and sympathetic tone are higher in the morning, physical activity and exercise in the afternoon has been recommended for patients with cardiovascular diseases. However, there have been no reports concerning the superior effects of afternoon exercise on parasympathetic activity and sleep.

Design: This observational study was a post hoc comparison.

Methods: Patients' physical activity was measured for 1 month to determine their habits. Patients' HF index was measured by 24-h Holter electrocardiography. The study enrolled 56 patients. Each patient's morning step count (before lunch) and afternoon step count (between lunch and dinner) were compared. We adhered to the STROBE guidelines in the present study.

Results: Thirty-one patients took more steps in the morning, and 25 patients took more steps in the afternoon. The present study showed that those who took more steps in the afternoon had a significantly higher HF index during the first hour after sleep onset and during sleep than those who took more steps in the morning (p = .003, .047).

Conclusions: The present study showed that those who took more steps in the afternoon had a significantly higher HF index during the first hour after sleep onset and a higher HF index during sleep than those who took more steps in the morning.

Relevance To Clinical Practice: Exercise in the afternoon may improve the prognosis in patients with cardiovascular disease by not only preventing excessive blood pressure, afterload, and sympathetic tone but also positively influencing the parasympathetic system and sleep.
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http://dx.doi.org/10.1111/jocn.16018DOI Listing
August 2021

Fitness of sulfadoxine-resistant Plasmodium berghei harboring a single mutation in dihydropteroate synthase (DHPS).

Acta Trop 2021 Oct 15;222:106049. Epub 2021 Jul 15.

Department of Tropical Medicine and Parasitology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. Electronic address:

Genetic changes conferring drug resistance are generally believed to impose fitness costs to pathogens in the absence of the drug. However, the fitness of resistant parasites against sulfadoxine/pyrimethamine has been inconclusive in Plasmodium falciparum. This is because resistance is conferred by the complex combination of mutations in dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr), which makes it difficult to separately assess the extent and magnitude of the costs imposed by mutations in dhps and dhfr. To assess the fitness costs imposed by sulfadoxine resistance alone, we generated a transgenic rodent malaria parasite, P. berghei clone harboring an A394G mutation in dhps (PbDHPS-A394G), corresponding to the causative mutation for sulfadoxine resistance in P. falciparum (PfDHPS-A437G). A four-day suppressive test confirmed that the PbDHPS-A394G clone was resistant to sulfadoxine. PbDHPS-A394G and wild-type clones showed similar growth rates and gametocyte production. This observation was confirmed in competitive experiments in which PbDHPS-A394G and wild-type clones were co-infected into mice to directly assess the survival competition between them. In the mosquitoes, there were no significant differences in oocyst production between PbDHPS-A394G and wild-type. These results indicate that the PbDHPS-A394G mutation alters the parasites to sulfadoxine resistance but may not impose fitness disadvantages during the blood stages in mice and oocyst formation in mosquitoes. These results partly explain the persistence of the PfDHPS-A437G mutant in the natural parasite populations.
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http://dx.doi.org/10.1016/j.actatropica.2021.106049DOI Listing
October 2021

Isolation of Mutants With Reduced Susceptibility to Piperaquine From a Mutator of the Rodent Malaria Parasite .

Front Cell Infect Microbiol 2021 16;11:672691. Epub 2021 Jun 16.

Department of Tropical Medicine and Parasitology, Faculty of Medicine, Juntendo University, Tokyo, Japan.

Elucidation of the mechanisms of drug resistance in malaria parasites is crucial for combatting the emergence and spread of resistant parasites, which can be achieved by tracing resistance-associated mutations and providing useful information for drug development. Previously, we produced a novel genetic tool, a mutator (PbMut), whose base substitution rate is 36.5 times higher than that of wild-type parasites. Here, we report the isolation of a mutant with reduced susceptibility to piperaquine (PPQ) from PbMut under PPQ pressure by sequential nine-cycle screening and named it PbMut-PPQ-R-P9. The ED of PbMut-PPQ-R-P9 was 1.79 times higher than that of wild-type parasites, suggesting that its PPQ resistance is weak. In the 1 screen, recrudescence occurred in the mice infected with PbMut but not in those infected with wild-type parasites, suggesting earlier emergence of PPQ-resistant parasites from PbMut. Whole-genome sequence analysis of PbMut-PPQ-R-P9 clones revealed that eight nonsynonymous mutations were conserved in all clones, including N331I in , the gene encoding chloroquine resistance transporter (). The PbCRT(N331I) mutation already existed in the parasite population after the 2 screen and was predominant in the population after the 8 screen. An artificially inserted PbCRT(N331I) mutation gave rise to reduced PPQ susceptibility in genome-edited parasites (PbCRT-N331I). The PPQ susceptibility and growth rates of PbCRT-N331I parasites were significantly lower than those of PbMut-PPQ-R-P9, implying that additional mutations in the PbMut-PPQ-R9 parasites could compensate for the fitness cost of the PbCRT(N331I) mutation and contribute to reduced PPQ susceptibility. In summary, PbMut could serve as a novel genetic tool for predicting gene mutations responsible for drug resistance. Further study on PbMut-PPQ-R-P9 could identify genetic changes that compensate for fitness costs owing to drug resistance acquisition.
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http://dx.doi.org/10.3389/fcimb.2021.672691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242943PMC
July 2021

Decreased continuous sitting time increases heart rate variability in patients with cardiovascular risk factors.

PLoS One 2021 16;16(6):e0253399. Epub 2021 Jun 16.

Nagoya University Graduate School of Medicine, Higashi-ku, Nagoya, Japan.

Aim: The purpose of the present study was to elucidate the relationship between high-frequency heart rate variability (HF HRV) and continuous daytime sitting time in patients with cardiovascular risk factors such as mild hypertension and/or stable angina pectoris.

Background: Decreased HF HRV precedes the progression and worsening of cardiovascular diseases. Continuous sitting behavior is a major risk factor for developing metabolic syndrome and is associated with cardiovascular disease, diabetes mellitus, renal failure, sarcopenia and osteoporosis. Risk factors for cardiovascular disease can be affected by continuous daytime sitting behaviors.

Design: The present study design was a post-hoc comparison.

Methods: Patients treated at two different primary care clinics from 2014 to 2018 were enrolled in this study (n = 53). We assessed HF HRV and continuous sitting time using 24-hour Holter electrocardiography and an activity meter at baseline and 6 months. HF HRV was calculated during sleep.

Results: Sitting time had decreased in 22 patients (decreased group) and increased in 31 patients (increased group) after 6 months. The mean patient ages were 73.1 and 72.0 years in the decreased and increased sitting time groups, respectively (p = 0.503). HF HRV during sleep had increased after 6 months in the decreased sitting time group. Compared with the increased group, the decreased group showed significantly higher HF HRV during sleep after 6 months by two-way repeated-measures ANOVA after adjustment for age, sex and change in activity (p = 0.045).

Conclusion: These results suggest that a decrease in sitting time might induce parasympathetic activity during sleep. Therefore, reducing continuous sitting time during the day might contribute, in part, to improving the prognosis of patients with cardiovascular risk factors not only by avoiding muscle loss but also by providing positive influences on parasympathetic tone during sleep.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253399PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208552PMC
June 2021

Postulated Process of Axoneme Organization in the Male Gametogenesis of Malaria Parasite .

Zoolog Sci 2021 Apr;38(2):187-192

Department of Biological Science, Graduate School of Arts and Sciences, the University of Tokyo, Komaba, Meguro-ku, Tokyo 153-8902, Japan.

The ultrastructural features of axoneme organization within the cytoplasm and exflagellation were investigated in detail in microgametes of a malaria parasite, by electron and fluorescence microscopy. The kinetosomes (basal bodies) of the microgamete were characterized by an electron dense mass in which singlet microtubules (MTs) were embedded. Around the kinetosomes, several singlet and doublet MTs were recognized in transverse sections. Incomplete doublets with growing B-tubule were also observed. As precursors of the axoneme, arrays of over three doublets showed a tendency to encircle the central pair MTs. Some of the doublet MTs were already equipped with inner and outer dynein arms. In the microgamete, which lacks an intraflagellar transport (IFT) system, self-assembly of microtubular and associated components appeared to proceed stepwise from singlet MTs through arrays of one to nine doublet MTs, surrounding the central pair, to form the complete axoneme in a quite short time. At exflagellation, some extra doublets were occasionally included between the axoneme and the flagellar membrane. At high magnification, the outer dynein arm of the microgamete had a pistol-like shape representing a three-headed dynein molecule like that of other Alveolata.
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http://dx.doi.org/10.2108/zs200064DOI Listing
April 2021

Ex vivo susceptibility of Plasmodium falciparum to antimalarial drugs in Northern Uganda.

Parasitol Int 2021 Apr 25;81:102277. Epub 2020 Dec 25.

Department of Tropical Medicine and Parasitology, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address:

In Uganda, artemether-lumefantrine was introduced as an artemisinin-based combination therapy (ACT) for malaria in 2006. We have previously reported a moderate decrease in ex vivo efficacy of lumefantrine in Northern Uganda, where we also detected ex vivo artemisinin-resistant Plasmodium falciparum. Therefore, it is necessary to search for candidate partner alternatives for ACT. Here, we investigated ex vivo susceptibility to four ACT partner drugs as well as quinine and chloroquine, in 321 cases between 2013 and 2018. Drug-resistant mutations in pfcrt and pfmdr1 were also determined. Ex vivo susceptibility to amodiaquine, quinine, and chloroquine was well preserved, whereas resistance to mefloquine was found in 45.8%. There were few cases of multi-drug resistance. Reduced sensitivity to mefloquine and lumefantrine was significantly associated with the pfcrt K76 wild-type allele, in contrast to the association between chloroquine resistance and the K76T allele. Pfmdr1 duplication was not detected in any of the cases. Amodiaquine, a widely used partner drug for ACT in African countries, may be the first promising alternative in case lumefantrine resistance emerges. Therapeutic use of mefloquine may not be recommended in this area. This study also emphasizes the need for sustained monitoring of antimalarial susceptibility in Northern Uganda to develop proper treatment strategies.
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http://dx.doi.org/10.1016/j.parint.2020.102277DOI Listing
April 2021

Emergence of artemisinin-resistant Plasmodium falciparum with kelch13 C580Y mutations on the island of New Guinea.

PLoS Pathog 2020 12 15;16(12):e1009133. Epub 2020 Dec 15.

Department of Tropical Medicine and Parasitology, Juntendo University Faculty of Medicine, Tokyo, Japan.

The rapid and aggressive spread of artemisinin-resistant Plasmodium falciparum carrying the C580Y mutation in the kelch13 gene is a growing threat to malaria elimination in Southeast Asia, but there is no evidence of their spread to other regions. We conducted cross-sectional surveys in 2016 and 2017 at two clinics in Wewak, Papua New Guinea (PNG) where we identified three infections caused by C580Y mutants among 239 genotyped clinical samples. One of these mutants exhibited the highest survival rate (6.8%) among all parasites surveyed in ring-stage survival assays (RSA) for artemisinin. Analyses of kelch13 flanking regions, and comparisons of deep sequencing data from 389 clinical samples from PNG, Indonesian Papua and Western Cambodia, suggested an independent origin of the Wewak C580Y mutation, showing that the mutants possess several distinctive genetic features. Identity by descent (IBD) showed that multiple portions of the mutants' genomes share a common origin with parasites found in Indonesian Papua, comprising several mutations within genes previously associated with drug resistance, such as mdr1, ferredoxin, atg18 and pnp. These findings suggest that a P. falciparum lineage circulating on the island of New Guinea has gradually acquired a complex ensemble of variants, including kelch13 C580Y, which have affected the parasites' drug sensitivity. This worrying development reinforces the need for increased surveillance of the evolving parasite populations on the island, to contain the spread of resistance.
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http://dx.doi.org/10.1371/journal.ppat.1009133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771869PMC
December 2020

Author Correction: CD8 T cell activation by murine erythroblasts infected with malaria parasites.

Sci Rep 2020 Nov 13;10(1):20195. Epub 2020 Nov 13.

Department of Parasitology, Graduate School of Medicine, Gunma University, Gunma, 371-8511, Japan.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-77423-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666112PMC
November 2020

Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda.

Malar J 2020 Feb 18;19(1):76. Epub 2020 Feb 18.

Department of Tropical Medicine and Parasitology, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.

Background: Usage of chloroquine was discontinued from the treatment of Plasmodium falciparum infection in almost all endemic regions because of global spread of resistant parasites. Since the first report in Malawi, numerous epidemiological studies have demonstrated that the discontinuance led to re-emergence of chloroquine-susceptible P. falciparum, suggesting a possible role in future malaria control. However, most studies were cross-sectional, with few studies looking at the persistence of chloroquine recovery in long term. This study fills the gap by providing, for a period of at least 6 years, proof of persistent re-emergence/stable recovery of susceptible parasite populations using both molecular and phenotypic methods.

Methods: Ex vivo drug-susceptibility assays to chloroquine (n = 319) and lumefantrine (n = 335) were performed from 2013 to 2018 in Gulu, Northern Uganda, where chloroquine had been removed from the official malaria treatment regimen since 2006. Genotyping of pfcrt and pfmdr1 was also performed.

Results: Chloroquine resistance (≥ 100 nM) was observed in only 3 (1.3%) samples. Average IC values for chloroquine were persistently low throughout the study period (17.4-24.9 nM). Parasites harbouring pfcrt K76 alleles showed significantly lower ICs to chloroquine than the parasites harbouring K76T alleles (21.4 nM vs. 43.1 nM, p-value = 3.9 × 10). Prevalence of K76 alleles gradually increased from 71% in 2013 to 100% in 2018.

Conclusion: This study found evidence of stable persistence of chloroquine susceptibility with the fixation of pfcrt K76 in Northern Uganda after discontinuation of chloroquine in the region. Accumulation of similar evidence in other endemic areas in Uganda could open channels for possible future re-use of chloroquine as an option for malaria treatment or prevention.
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http://dx.doi.org/10.1186/s12936-020-03157-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026951PMC
February 2020

Increased Activity in Patients with Cardiovascular Risk Factors Increases Heart Rate Variability.

West J Nurs Res 2020 06 22;42(6):431-436. Epub 2019 Jul 22.

Department of Nursing, Sugiyama Jogakuen University, Nagoya, Aichi, Japan.

This study evaluated the effect of increased physical activity on high-frequency (HF) heart rate variability (HRV) during the first hour after sleep onset in patients with hypertension and/or stable angina pectoris. Physical activity and HF were measured using activity monitors and 24-hour Holter monitors at baseline and 6 months later. The physical activity increased in 28 patients (increase group) and decreased in 20 patients (decrease group) after 6 months. In this study, after 6 months, compared to the decreased physical activity group, the increased physical activity group showed a significant increase in the HF index during the first hour after sleep onset. Therefore, the increase in the HF index may have been due to the increase in physical activity. An increase in physical activity suggests that the quality of sleep early in the sleep cycle may be improved, which may affect the patient's prognosis.
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http://dx.doi.org/10.1177/0193945919864700DOI Listing
June 2020

T-wave changes of cardiac memory caused by frequent premature ventricular contractions originating from the right ventricular outflow tract.

J Cardiovasc Electrophysiol 2019 09 25;30(9):1549-1556. Epub 2019 Jun 25.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Introduction: Cardiac memory is recognized as altered T-waves when the sinus rhythm resumes after an abnormal myocardial activation period that recovers slowly over several weeks. The T-wave changes after ablation of frequent premature ventricular contractions (PVCs) as cardiac memory was not known.

Objective: This study identified whether cardiac memory exists after successful ablation of PVCs from the right ventricular outflow tract (RVOT).

Methods: We investigated 45 patients who underwent successful ablation of PVCs from RVOT and 10 patients who underwent unsuccessful ablation. We analyzed the amplitude of the T-wave, QT intervals, and QRST time-integral values of a 12-lead electrocardiogram before ablation and 1 day, 3 days, and 1 month after ablation.

Results: In the successful ablation group, the amplitude of the T-wave and QRST time-integral values of lead II, III, aVR, aVL, and aVF significantly changed after ablation and gradually normalized within 1 month. In addition, if the number of pre-ablation PVCs was small, then the corresponding impact was also small. However, the greater the number of pre-ablation PVCs, the more prominent the changes. Significant changes were not observed in the unsuccessful ablation group.

Conclusion: When ablation of PVCs from RVOT was successful, primary T-wave changes because of cardiac memory and the gradual normalization of the amplitude of the T-wave were observed. No significant T-wave changes were detected after unsuccessful ablation.
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http://dx.doi.org/10.1111/jce.14008DOI Listing
September 2019

See-through observation of malaria parasite behaviors in the mosquito vector.

Sci Rep 2019 02 11;9(1):1768. Epub 2019 Feb 11.

Department of Molecular and Cellular Parasitology, Juntendo University, 2-1-1 Hongo, Bunkyo, Tokyo, Japan.

Although it is known that malaria parasites proliferate in the midgut of mosquito vector, their detailed behaviors, from gamete maturation to formation of next generation sporozoite, have not been fully understood at cellular or molecular level. This is mainly attributed to technical difficulties of dissection and whole-mount observation, of delicate and opaque mosquito body contents. In addition, blood pigment surrounding parasites immediately after blood meal also complicates tracing mosquito-stage parasites. Recent revolutionary studies have overcome such negative factors in tissue observation by clearing organisms. CUBIC reagents succeeded to remove both light scattering and blood pigment from various mouse tissues, and to whole-organ image fluorescence-labeled cell structures. In this study, we utilized the advanced version of CUBIC technology and high sensitivity fluorescent markers for see-through observation of mosquito vector after engulfment of rodent malaria parasites to clarify their behaviors during mosquito stage. As a result, we succeeded to visualize oocysts, sporozoites, female gametes and ookinetes in the mosquito bodies without any dissection.
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http://dx.doi.org/10.1038/s41598-019-38529-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370880PMC
February 2019

Napping Improves HRV in Older Patients With Cardiovascular Risk Factors.

West J Nurs Res 2019 09 11;41(9):1241-1253. Epub 2019 Jan 11.

5 Sugiyama Jogakuen University, Nagoya, Japan.

Heart rate variability (HRV), especially increased high frequency (HF), has been reported to provide clinically useful prognostic information regarding cardiovascular disease. Napping is an excellent sleep management strategy in older adults. This study was conducted to clarify the effect of napping on HRV in older adult patients with cardiovascular risk factors. The patients were divided into two groups: one group of 32 patients who reported napping (nap group) and another group of 45 patients who did not report napping (nonnap group). The HRV was calculated in terms of the HF component over 24 hr during wakefulness, sleep, and 1 hr after sleep onset. The HF in the nap group was significantly higher than that in the nonnap group during all times measured. In addition, napping was a significant predictor of increased HF. This study shows the effectiveness of napping in the daily lives of patients with cardiovascular risk factors.
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http://dx.doi.org/10.1177/0193945918824603DOI Listing
September 2019

Lack of significant recovery of chloroquine sensitivity in Plasmodium falciparum parasites following discontinuance of chloroquine use in Papua New Guinea.

Malar J 2018 Nov 26;17(1):434. Epub 2018 Nov 26.

Department of Tropical Medicine and Parasitology, Juntendo University, Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Background: Chloroquine treatment for Plasmodium falciparum has been discontinued in almost all endemic regions due to the spread of resistant isolates. Reversal of chloroquine susceptibility after chloroquine discontinuation has been reported in dozens of endemic regions. However, this phenomenon has been mostly observed in Africa and is not well documented in other malaria endemic regions. To investigate this, an ex vivo study on susceptibility to chloroquine and lumefantrine was conducted during 2016-2018 in Wewak, Papua New Guinea where chloroquine had been removed from the official malaria treatment regimen in 2010. Genotyping of pfcrt and pfmdr1 was also performed.

Results: In total, 368 patients were enrolled in this study. Average IC values for chloroquine were 106.6, 80.5, and 87.6 nM in 2016, 2017, and 2018, respectively. These values were not significantly changed from those obtained in 2002/2003 (108 nM). The majority of parasites harboured a pfcrt K76T the mutation responsible for chloroquine resistance. However, a significant upward trend was observed in the frequency of the K76 (wild) allele from 2.3% in 2016 to 11.7% in 2018 (P = 0.008; Cochran-Armitage trend test).

Conclusions: Eight years of chloroquine withdrawal has not induced a significant recovery of susceptibility in Papua New Guinea. However, an increasing tendency of parasites harbouring chloroquine-susceptible K76 suggests a possibility of resurgence of chloroquine susceptibility in the future.
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http://dx.doi.org/10.1186/s12936-018-2585-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6260888PMC
November 2018

Artemisinin-Resistant Plasmodium falciparum with High Survival Rates, Uganda, 2014-2016.

Emerg Infect Dis 2018 04;24(4):718-726

Because ≈90% of malaria cases occur in Africa, emergence of artemisinin-resistant Plasmodium falciparum in Africa poses a serious public health threat. To assess emergence of artemisinin-resistant parasites in Uganda during 2014-2016, we used the recently developed ex vivo ring-stage survival assay, which estimates ring-stage-specific P. falciparum susceptibility to artemisinin. We conducted 4 cross-sectional surveys to assess artemisinin sensitivity in Gulu, Uganda. Among 194 isolates, survival rates (ratio of viable drug-exposed parasites to drug-nonexposed controls) were high (>10%) for 4 isolates. Similar rates have been closely associated with delayed parasite clearance after drug treatment and are considered to be a proxy for the artemisinin-resistant phenotype. Of these, the PfKelch13 mutation was observed in only 1 isolate, A675V. Population genetics analysis suggested that these possibly artemisinin-resistant isolates originated in Africa. Large-scale surveillance of possibly artemisinin-resistant parasites in Africa would provide useful information about treatment outcomes and help regional malaria control.
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http://dx.doi.org/10.3201/eid2404.170141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875287PMC
April 2018

Mutation tendency of mutator Plasmodium berghei with proofreading-deficient DNA polymerase δ.

Sci Rep 2016 11 15;6:36971. Epub 2016 Nov 15.

Department of Molecular and Cellular Parasitology, Juntendo University, 2-1-1 Hongo, Bunkyo, Tokyo, Japan.

In this study, we investigated the mutation tendency of a mutator rodent malaria parasite, Plasmodium berghei, with proofreading-deficient DNA polymerase δ. Wild-type and mutator parasites were maintained in mice for over 24 weeks, and the genome-wide accumulated mutations were determined by high-throughput sequencing. The mutator P. berghei had a significant preference for C/G to A/T substitutions; thus, its genome had a trend towards a higher AT content. The mutation rate was influenced by the sequence context, and mutations were markedly elevated at TCT. Some genes mutated repeatedly in replicate passage lines. In particular, knockout mutations of the AP2-G gene were frequent, which conferred strong growth advantages on parasites during the blood stage but at the cost of losing the ability to form gametocytes. This is the first report to demonstrate a biased mutation tendency in malaria parasites, and its results help to promote our basic understanding of Plasmodium genetics.
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http://dx.doi.org/10.1038/srep36971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5109483PMC
November 2016

An ECG Index of P-Wave Force Predicts the Recurrence of Atrial Fibrillation after Pulmonary Vein Isolation.

Pacing Clin Electrophysiol 2016 Nov 2;39(11):1191-1197. Epub 2016 Nov 2.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: Although several prognostic factors of atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI) have been investigated, the accurate prediction of AF recurrence remains difficult. We propose an electrocardiogram (ECG) index, the P-wave force (PWF), which is the product of the amplitude of the negative terminal phase of the P wave in the V1 electrode and the filtered P-wave duration, obtained by a signal-averaged P-wave analysis. This study was conducted to evaluate the impact of the PWF on the recurrence of AF after PVI.

Methods: We retrospectively evaluated 79 paroxysmal AF patients (64 ± 9 years, 56 males) who underwent PVI by cryoballoon ablation. Standard 12-lead ECG and a P-wave signal-averaged electrocardiogram (SAECG) were recorded the day before and 1 month after the PVI procedure.

Results: During the mean follow-up of 10.2 months, AF recurred in 11 (14%) patients. The PWF 1 month after ablation was significantly higher in the recurrence group compared to that in the nonrecurrence group (8.8 ± 3.1 mVms vs 6.5 ± 2.9 mVms, P = 0.017). The patients with a PWF value ≥9.3 mVms had a significantly greater risk of recurrence after the ablation compared to the patients with a PWF value <9.3 mVms (log-rank test, P < 0.001).

Conclusion: Higher PWF after cryoballoon ablation was associated with poor prognosis during follow-up. The PWF may be a useful and noninvasive marker to predict the recurrence of AF.
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http://dx.doi.org/10.1111/pace.12956DOI Listing
November 2016

Impaired renal function is associated with recurrence after cryoballoon catheter ablation for paroxysmal atrial fibrillation: A potential effect of non-pulmonary vein foci.

J Cardiol 2017 01 5;69(1):3-10. Epub 2016 Aug 5.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: Atrial fibrillation (AF) and chronic kidney disease (CKD) are closely related. The present study aimed to evaluate the association between estimated glomerular filtration rate (eGFR) and outcomes after cryoballoon catheter ablation for AF.

Methods: We included a total of 110 patients (64.0±10.1 years, 64% men) with paroxysmal AF who underwent second-generation cryoballoon catheter ablation in this study. Recurrence and change in renal function after ablation were assessed by stratification of eGFR sub-groups.

Results: During a mean follow-up period of 9 months, 20 (18%) patients had AF recurrence after the first catheter ablation procedure. Multivariate Cox regression analysis showed that eGFR [hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.93-0.99, p=0.047], non-pulmonary vein (PV) ectopic beats at initial ablation (HR 2.92, 95% CI 1.03-8.27, p=0.043), and history of stroke (HR 7.47, 95% CI 2.30-24.2, p=0.001) were independent predictors of recurrence after the ablation. Among the CKD groups, recurrence was found in 7% (1/15), 12% (9/73), and 46% (10/22) of the eGFR ≥90mL/min/1.73m, eGFR 60-89.9mL/min/1.73m, and eGFR 30-59.9mL/min/1.73m groups, respectively (p=0.001). Kaplan-Meier survival curves demonstrated that patients with eGFR 30-59.9mL/min/1.73m had significantly worse prognosis than did the other groups (log-rank p<0.001). In addition, non-PV ectopic beats at initial ablation were detected in 7% (1/15), 14% (10/73), and 50% (11/22) of the patients among the three CKD groups, respectively (p<0.001). No patients developed contrast-induced nephropathy after the catheter ablation procedure.

Conclusions: Low eGFR at baseline was an independent predictor of recurrence after cryoballoon ablation for paroxysmal AF. The presence of non-PV ectopic beats was significantly increased in patients with impaired renal function, which might be associated with a poor outcome.
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http://dx.doi.org/10.1016/j.jjcc.2016.07.008DOI Listing
January 2017

Effect and Significance of Early Reablation for the Treatment of Early Recurrence of Atrial Fibrillation After Catheter Ablation.

Am J Cardiol 2016 09 29;118(6):833-841. Epub 2016 Jun 29.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

There are few reports on early reablation (ER) for early recurrence of atrial fibrillation (AF) after catheter ablation. The present study evaluated the efficacy and significance of ER for early recurrence within a blanking period of 3 months after ablation of both paroxysmal and persistent AF, using a propensity-matched analysis. Of 874 patients who underwent catheter ablation of AF, 389 (45%) had early recurrence. Of these, 78 patients underwent an ER procedure. A total of 132 matched patients (66 in the ER and 66 in the non-ER groups, 82 patients with paroxysmal AF) were included in the analysis. During a mean follow-up of 15.4 months, the patients who underwent ER had a significantly lower recurrence rate than those who did not (29 [44%] vs 42 patients [64%], p = 0.023). The benefit of ER was especially apparent in patients with paroxysmal AF (p = 0.008) but not in those with persistent AF (p = 0.774). However, 24 patients (36%) in the non-ER group did not experience recurrence after a blanking period without any reablation procedure. The total number of reablation sessions was higher in the ER group than in the non-ER group (1.2 ± 0.5 vs 0.4 ± 0.6, p <0.001). Nonetheless, mean number of arrhythmia outpatient clinic visits at follow-up was significantly fewer in the ER group than in the late reablation group. In conclusion, ER for early recurrence of AF after catheter ablation might be effective for preventing recurrence during follow-up, especially for paroxysmal AF.
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http://dx.doi.org/10.1016/j.amjcard.2016.06.045DOI Listing
September 2016

Plasmodium Rab5b is secreted to the cytoplasmic face of the tubovesicular network in infected red blood cells together with N-acylated adenylate kinase 2.

Malar J 2016 06 17;15:323. Epub 2016 Jun 17.

Department of Parasitology, National Institute of Infectious Diseases, Shinjuku-Ku, Tokyo, Japan.

Background: Rab5 GTPase regulates membrane trafficking between the plasma membrane and endosomes and harbours a conserved C-terminal isoprenyl modification that is necessary for membrane recruitment. Plasmodium falciparum encodes three Rab5 isotypes, and one of these, Rab5b (PfRab5b), lacks the C-terminal modification but possesses the N-terminal myristoylation motif. PfRab5b was reported to localize to the parasite periphery. However, the trafficking pathway regulated by PfRab5b is unknown.

Methods: A complementation analysis of Rab5 isotypes was performed in Plasmodium berghei. A constitutively active PfRab5b mutant was expressed under the regulation of a ligand-dependent destabilization domain (DD)-tag system in P. falciparum. The localization of PfRab5b was evaluated after removing the ligand followed by selective permeabilization of the membrane with different detergents. Furthermore, P. falciparum N-terminally myristoylated adenylate kinase 2 (PfAK2) was co-expressed with PfRab5b, and trafficking of PfAK2 to the parasitophorous vacuole membrane was examined by confocal microscopy.

Results: PfRab5b complemented the function of PbRab5b, however, the conventional C-terminally isoprenylated Rab5, PbRab5a or PbRab5c, did not. The constitutively active PfRab5b mutant localized to the cytosol of the parasite and the tubovesicular network (TVN), a region that extends from the parasitophorous vacuole membrane (PVM) in infected red blood cells (iRBCs). By removing the DD-ligand, parasite cytosolic PfRab5b signal disappeared and a punctate structure adjacent to the endoplasmic reticulum (ER) and parasite periphery accumulated. The peripheral PfRab5b was sensitive to extracellular proteolysis after treatment with streptolysin O, which selectively permeabilizes the red blood cell plasma membrane, indicating that PfRab5b localized on the iRBC cytoplasmic face of the TVN. Transport of PfAK2 to the PVM was abrogated by overexpression of PfRab5b, and PfAK2 accumulated in the punctate structure together with PfRab5b.

Conclusion: N-myristoylated Plasmodium Rab5b plays a role that is distinct from that of conventional mammalian Rab5 isotypes. PfRab5b localizes to a compartment close to the ER, translocated to the lumen of the organelle, and co-localizes with PfAK2. PfRab5b and PfAK2 are then transported to the TVN, and PfRab5b localizes on the iRBC cytoplasmic face of TVN. These data demonstrate that PfRab5b is transported from the parasite cytosol to TVN together with N-myristoylated PfAK2 via an uncharacterized membrane-trafficking pathway.
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http://dx.doi.org/10.1186/s12936-016-1377-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912828PMC
June 2016

Elevated Red Blood Cell Distribution Width Predicts Recurrence After Catheter Ablation for Atrial Fibrillation in Patients With Heart Failure - Comparison With Non-Heart Failure Patients.

Circ J 2016 26;80(3):627-38. Epub 2016 Jan 26.

Department of Cardiology, Nagoya University Graduate School of Medicine.

Background: Elevated red blood cell distribution width (RDW) predicts poor prognosis in patients with cardiovascular diseases. However, little is known about the association between RDW and outcomes after catheter ablation of atrial fibrillation (AF).

Methods and results: A total of 757 patients who underwent radiofrequency catheter ablation of AF were divided into heart failure (HF, n=79) and non-HF (n=678) groups; RDW was assessed as a predictor after catheter ablation in each. During a 22.3-month follow-up period, the baseline RDW in the HF group was greater in the recurrence group than in the non-recurrence group (14.5±2.0% vs. 13.5±0.9%, P=0.013). In contrast, no significant difference in RDW at baseline was found in the non-HF group between the recurrence and non-recurrence groups (13.3±0.8% vs. 13.2±0.8%, P=0.332, respectively). Multivariate analysis demonstrated that RDW (hazard ratio 1.20, 95% confidence interval 1.01-1.40, P=0.034) was an independent predictor of AF recurrence in the HF group. The cut-off values of RDW for the recurrence of AF and major adverse events in the HF group were 13.9% and 14.8%, respectively.

Conclusions: High RDW is an independent predictor for the recurrence of AF and major adverse events in patients with HF after catheter ablation. RDW is a potential noninvasive marker in AF patients complicated with HF. (Circ J 2016; 80: 627-638).
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http://dx.doi.org/10.1253/circj.CJ-15-1152DOI Listing
November 2016

Decrease in B-Type Natriuretic Peptide Levels and Successful Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure.

Pacing Clin Electrophysiol 2016 Mar 24;39(3):225-34. Epub 2015 Dec 24.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: Little is known about the association between B-type natriuretic peptide (BNP) levels and catheter ablation of atrial fibrillation (AF) in patients with heart failure. This study aimed to examine the impact of elimination of AF by catheter ablation on BNP levels in patients with left ventricular systolic dysfunction.

Methods: Fifty-four AF patients with left ventricular ejection fraction (LVEF) ≤ 50%, who underwent radiofrequency catheter ablation therapy of AF, were included. BNP sampling was performed at baseline, 3 days, and 1 month after ablation.

Results: After a follow-up period of 6 months, the BNP levels decreased significantly in the nonrecurrence group (n = 35; median 126.3 [interquartile 57.2-206.5] pg/mL, 63.5 [23.9-180.2] pg/mL, and 45.9 [21.9-160.3] pg/mL, P < 0.001, respectively), but not in the recurrence group (n = 19; 144.7 [87.1-217.3] pg/mL, 88.8 [12.9-213.2] pg/mL, and 118.5 [51.6-298.2] pg/mL, P = 0.368, respectively). The patients in the nonrecurrence group had a higher percentage relative reduction in BNP levels from baseline to 1 month after ablation than those in the recurrence group (56.5 [-9.0-77.4]% vs -2.4 [-47.1-60.9]%, P = 0.027). Additionally, a relative reduction in BNP levels significantly correlated with an increase in LVEF after ablation (r = 0.486, P < 0.001).

Conclusions: Plasma BNP levels decreased significantly with successful catheter ablation of AF in patients with impaired LVEF. The decrease in BNP levels might be associated with early recovery of cardiac function and subsequent maintenance of sinus rhythm at follow-up.
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http://dx.doi.org/10.1111/pace.12788DOI Listing
March 2016

Plasmodium falciparum kelch 13: a potential molecular marker for tackling artemisinin-resistant malaria parasites.

Expert Rev Anti Infect Ther 2016 4;14(1):125-35. Epub 2015 Nov 4.

a Department of Molecular and Cellular Parasitology , Juntendo University School of Medicine , Tokyo , Japan.

Although artemisinin combination therapies have been deployed as a first-line treatment for uncomplicated malaria in almost all endemic countries, artemisinin-resistant parasites have emerged and have gradually spread across the Greater Mekong subregions. There is growing concern that the resistant parasites may migrate to or emerge indigenously in sub-Saharan Africa, which might provoke a global increase in malaria-associated morbidity and mortality. Therefore, development of molecular markers that enable identification of artemisinin resistance with high sensitivity is urgently required to combat this issue. In 2014, a potential artemisinin-resistance responsible gene, Plasmodium falciparum kelch13, was discovered. Here, we review the genetic features of P. falciparum kelch13 and discuss its related resistant mechanisms and potential as a molecular marker.
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http://dx.doi.org/10.1586/14787210.2016.1106938DOI Listing
October 2016

Effects of Defecation Strain at Various Bed Reclining Angles on Intrarectal Pressure and Cardiovascular Responses.

Nurs Res 2015 Nov-Dec;64(6):413-21

Mika Imai, RN, MS, is Assistant Professor, Department of Nursing, Ogaki Women's College, and Department of Nursing, Nagoya University School of Health Sciences, Japan. Yuko Kuwahara, DVM, PhD, is Research Associate, Department of Physiology, Aichi Medical University, Nagakute, Japan. Makoto Hirai, MD, PhD, is Professor, Department of Nursing, Nagoya University School of Health Sciences, Japan. Rumiko Nishimura, MS, is PhD Candidate; Naoki Nishimura, PhD, is Assistant Professor; and Yuuki Shimizu, PhD, is Assistant Professor, Department of Physiology, Aichi Medical University, Nagakute, Japan. Tetsuya Fujii, RN, PhD, is Professor, Department of Nursing, Seirei Christopher University, Hamamatsu, Japan. Satoshi Iwase, MD, PhD, is Professor, Department of Physiology, Aichi Medical University, Nagakute, Japan.

Background: There is no clear information about the optimal bed reclining angle for promoting efficient and safe defecation in bedfast patients.

Objective: The aim of this study was to examine the optimal bed reclining angle for facilitating increases in intrarectal pressure without causing marked cardiovascular changes in order to develop an efficient and safe defecation position for bedfast patients.

Methods: Twelve healthy men participated in this study. The subjects were required to strain for 15 seconds at the end stage of inspiration while their bed was reclined at 0° (supine), 15°, 30°, or 60°. During straining, the subjects were asked to maintain (a) an intrarectal pressure of 20 mm Hg or (b) the maximal intrarectal pressure. Intrarectal pressure, blood pressure, heart rate, and abdominal muscle activity (electromyographic activity) were recorded continuously throughout the study period.

Results: During straining, intrarectal pressure increased with the reclining angle, and a significant linear correlation was detected between the sine of the reclining angle of the bed and intrarectal pressure (η = .57, p < .01). When subjects were straining with the aim of maintaining maximal intrarectal pressure, the extent of the observed changes (delta) in blood pressure and heart rate did not differ significantly across the reclining angles. When subjects were straining with the aim of maintaining an intrarectal pressure of 20 mm Hg, the delta blood pressure decreased as the reclining angle increased 0°: M = 23.7, SD = 15.3 mm Hg, 95% CI [11.9, 35.4]; 15°: M = 25.9, SD = 10.8 mm Hg, 95% CI [17.6, 34.2]; 30°: M = 17.7, SD = 9.4 mm Hg, 95% CI [10.4, 24.9]; 60°: M = 15.5, SD = 9.5 mm Hg, 95% CI [8.1, 22.8]; 15° versus 30°: p < .05; 15° versus 60°: p < .05. The amount of muscle activity observed during straining decreased as the reclining angle increased.

Discussion: In bedfast patients, it is suggested that higher reclining angles may enable safer and more efficient defecation, because it decreases the amount of muscle activity required to increase the intrarectal pressure and reduces the potentially deleterious effects of straining on the cardiovascular system to develop an efficient and safe defecation position for bedfast patients.
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http://dx.doi.org/10.1097/NNR.0000000000000118DOI Listing
February 2016

Plasmodium berghei ANKA causes intestinal malaria associated with dysbiosis.

Sci Rep 2015 Oct 27;5:15699. Epub 2015 Oct 27.

Department of Parasitology, Graduate School of Medicine, Gunma University, 3-39-22, Showa-machi, Maebashi, Gunma 371-8511, Japan.

Gastrointestinal symptoms, such as abdominal pain and diarrhea, are frequently observed in patients with Plasmodium falciparum malaria. However, the correlation between malaria intestinal pathology and intestinal microbiota has not been investigated. In the present study, infection of C57BL/6 mice with P. berghei ANKA (PbA) caused intestinal pathological changes, such as detachment of epithelia in the small intestines and increased intestinal permeability, which correlated with development with experimental cerebral malaria (ECM). Notably, an apparent dysbiosis occurred, characterized by a reduction of Firmicutes and an increase in Proteobacteria. Furthermore, some genera of microbiota correlated with parasite growth and/or ECM development. By contrast, BALB/c mice are resistant to ECM and exhibit milder intestinal pathology and dysbiosis. These results indicate that the severity of cerebral and intestinal pathology coincides with the degree of alteration in microbiota. This is the first report demonstrating that malaria affects intestinal microbiota and causes dysbiosis.
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http://dx.doi.org/10.1038/srep15699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621605PMC
October 2015

Body mass index is associated with prognosis in Japanese elderly patients with atrial fibrillation: an observational study from the outpatient clinic.

Heart Vessels 2016 Sep 26;31(9):1553-61. Epub 2015 Oct 26.

Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.

The relationship between body mass index (BMI) and the prognosis of elderly patients with atrial fibrillation (AF) is unknown. We aimed to examine the association of body weight with the clinical outcomes among Japanese elderly patients with a history of documented AF. This observational study of AF patients from an outpatients clinic in Nagoya University Hospital included 413 patients ≥70 years old (99 obese: BMI ≥25 kg/m(2); 256 normal weight: BMI 18.5-24.9 kg/m(2); and 58 underweight patients: BMI <18.5 kg/m(2)). The mean age was 77.5 ± 5.6 years. During a mean follow-up of 19.0 months, all-cause death occurred in 23 patients (obese 1 %, normal weight 5.1 %, and underweight 16 %). The major adverse events including all-cause death, stroke or transient ischemic attack, heart failure requiring admission, and acute coronary syndrome were observed in 53 patients (obese 5.1 %, normal weight 13 %, and underweight 26 %). After adjusting for confounding factors, the underweight group had a significantly greater risk for all-cause death [hazard ratio (HR) 2.91, 95 % confidence interval (CI) 1.12-7.60, p = 0.029], and major adverse events (HR 2.45, 95 % CI 1.25-4.78, p = 0.009) than the normal weight group. In contrast, the obese group had a better prognosis in major adverse events compared with the normal weight group (HR 0.34, 95 % CI 0.13-0.89, p = 0.029). In conclusion, lower BMI was independently associated with poor outcomes among older AF patients. The association between obesity and better prognosis in elderly AF patients was also found.
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http://dx.doi.org/10.1007/s00380-015-0765-yDOI Listing
September 2016

Impact of cardiac resynchronization therapy-defibrillator implantation on the association between body mass index and prognosis in patients with heart failure.

J Interv Card Electrophysiol 2015 Sep 24;43(3):269-77. Epub 2015 May 24.

Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.

Purpose: This study aimed to examine the association between body mass index (BMI) and prognosis in heart failure patients after cardiac resynchronization therapy-defibrillator (CRT-D) implantation.

Methods: We retrospectively investigated 125 patients (33 overweight [BMI ≥25 kg/m(2)], 75 normal weight [BMI 18.5-24.9 kg/m(2)], and 17 underweight patients [BMI <18.5 kg/m(2)]) who underwent CRT-D implantation. The clinical outcome endpoints were all-cause death and appropriate shock therapy.

Results: During the follow-up period (mean 3.1 ± 1.8 years), 23 patients died (1 [3.0 %] overweight, 17 [22.7 %] normal weight, and 5 [29.4 %] underweight patients), and appropriate shock events were observed in 14 patients (2 [6.1 %] overweight, 10 [13.3 %] normal weight, and 2 [11.8 %] underweight patients). All patients survived shock therapy. After adjusting for confounding factors, overweight patients had significantly fewer outcomes relating to all-cause death and appropriate shock events (hazard ratio 0.27, 95 % confidence interval 0.08-0.91, p = 0.034) than normal weight patients. However, the prognostic difference between overweight and normal weight patients could be diminished as a result of the successful shock therapies (p = 0.067). Additionally, prognosis did not differ between overweight and normal weight patients among the responders, but did differ among the non-responders. The underweight patients had a poorer prognosis after CRT-D implantation compared with the other groups.

Conclusions: Although high BMI was associated with better outcomes among heart failure patients with CRT-D implantations, the difference in the prognosis between overweight and normal weight patients was reduced because of defibrillator therapy and the improvement in cardiac function provided by CRT-D implantation.
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http://dx.doi.org/10.1007/s10840-015-0015-3DOI Listing
September 2015

Feasibility and safety of uninterrupted dabigatran therapy in patients undergoing ablation for atrial fibrillation.

Intern Med 2015 15;54(10):1167-73. Epub 2015 May 15.

Department of Cardiology, Nagoya University Graduate School of Medicine, Japan.

Objective: Uninterrupted oral warfarin strategy has become the standard protocol to prevent complications during catheter ablation (CA) for the treatment of atrial fibrillation (AF). However, little is known about the safety and efficacy of uninterrupted dabigatran therapy in patients undergoing CA for AF. Therefore, this study investigated the safety and efficacy of uninterrupted dabigatran therapy and compared the findings with those for uninterrupted warfarin therapy.

Methods: Bleeding and thromboembolic events during the periprocedural period were evaluated in 363 consecutive patients who underwent CA for AF at Nagoya University Hospital, and received uninterrupted dabigatran (n=173) or uninterrupted warfarin (n=190) for periprocedural anticoagulation.

Results: A total of 27 (7%) patients experienced either bleeding or thromboembolic complications. Major bleeding complications occurred in 2 (1%) patients in the dabigatran group (DG) and 2 (1%) patients in the warfarin group (WG). Eight (5%) patients in the DG and 9 (5%) patients in the WG experienced groin hematoma, a type of minor bleeding complication. Meanwhile, no patient in the DG and 1 (1%) in the WG developed cerebral ischemic stroke. Overall, there was no significant difference between the groups for any category. The activated partial thromboplastin time (APTT) independently predicted periprocedural complications in the DG.

Conclusion: Uninterrupted dabigatran therapy in CA for AF thus may be a safe and effective anticoagulant therapy, and appears to be closely similar to continuous warfarin; however, it is essential to pay close attention to the APTT values when using dabigatran during CA.
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http://dx.doi.org/10.2169/internalmedicine.54.3520DOI Listing
October 2015

Differences in activated clotting time among uninterrupted anticoagulants during the periprocedural period of atrial fibrillation ablation.

Heart Rhythm 2015 Sep 13;12(9):1972-8. Epub 2015 Apr 13.

Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Background: Close monitoring of intraoperative activated clotting time (ACT) is crucial to prevent complications during the periprocedural period of atrial fibrillation (AF) ablation. However, little is known about the ACT in patients receiving new oral anticoagulant agents (NOACs).

Objective: The purpose of this study was to evaluate change in the ACT among anticoagulant agents used during the periprocedural period of AF ablation.

Methods: We examined 869 consecutive patients who underwent AF ablation between April 2012 and August 2014 and received NOACs (n = 499), including dabigatran, rivaroxaban, and apixaban, or warfarin (n = 370) for uninterrupted periprocedural anticoagulation. Changes in intraprocedural ACT were investigated among the anticoagulant agents. Furthermore, the incidence of periprocedural events was estimated.

Results: The average time in minutes required for achieving a target ACT >300 seconds was significantly longer in the dabigatran group (DG) and apixaban group (AG) than in the warfarin group (WG) and rivaroxaban group (RG) (60 and 70 minutes vs 8 and 9 minutes, respectively; P < .001). In addition, the proportion of patients who achieved the target ACT after initial heparin bolus was significantly lower in the DG and AG than in the WG and RG (36% and 26% vs 84% and 78%, respectively; P < .001). Furthermore, the incidence of periprocedural complications was equivalent among the groups.

Conclusion: The average time required to reach the target ACT was longer in the DG and AG than in the WG and RG.
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http://dx.doi.org/10.1016/j.hrthm.2015.04.016DOI Listing
September 2015
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