Publications by authors named "Kazutaka Aonuma"

438 Publications

Pulmonary Artery Isolation for Polymorphic Outflow Tract Ventricular Tachycardia.

JACC Case Rep 2021 Nov 17;3(16):1738-1742. Epub 2021 Nov 17.

Department of Cardiology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.

Malignant ventricular arrhythmias arising from the pulmonary artery rarely occur in patients without structural heart disease. We highlight the feasibility and efficacy of a circular catheter-guided pulmonary artery isolation procedure for frequent premature ventricular contractions and polymorphic ventricular tachycardia causing syncope. ().
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http://dx.doi.org/10.1016/j.jaccas.2021.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8603021PMC
November 2021

Increased serum amiodarone concentration in hypertriglyceridemic patients: Effects of drug distribution to serum lipoproteins.

Clin Transl Sci 2021 Nov 16. Epub 2021 Nov 16.

Department of Pharmacy, University of Tsukuba Hospital, Tsukuba, Japan.

Amiodarone and its main metabolite, desethylamiodarone (DEA), are highly distributed to serum lipoproteins such as very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), which are the carriers of triglyceride and cholesterol. This study aimed to investigate the association of serum concentrations of amiodarone and DEA with the levels of serum lipids in terms of drug distribution to lipoprotein fractions in patients with hyperlipidemia. Total serum concentrations of amiodarone and DEA were examined in 116 patients receiving amiodarone for tachyarrhythmias. The concentration-to-dose (C/D) ratio of amiodarone positively correlated with the level of serum triglyceride (r  = 0.541, p < 0.001) and was higher in the hypertriglyceridemic state than in normotriglyceridemic state (479 ± 211 vs. 320 ± 161, p < 0.001). No correlation was found between the C/D ratio of DEA and serum triglyceride levels (r  = 0.272), although higher values were observed in the hypertriglyceridemic state (322 ± 125 vs. 285 ± 143, p < 0.001). In the hypertriglyceridemic state, the distribution of amiodarone increased in LDL/VLDL fraction and decreased in high-density lipoprotein and albumin fractions. The ratio of serum amiodarone to serum DEA, a metabolic ratio of amiodarone, positively correlated with serum triglyceride levels (r  = 0.572, p < 0.001) and was higher in the hypertriglyceridemic state, suggesting that amiodarone metabolism decreased in hyperlipidemia. The results of this study reveal that serum concentrations of amiodarone increase in the hypertriglyceridemic state through the increased lipoprotein-binding and decreased metabolism of amiodarone.
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http://dx.doi.org/10.1111/cts.13199DOI Listing
November 2021

Correction: Feng et al. Nicotinamide Phosphoribosyltransferase (Nampt)/Nicotinamide Adenine Dinucleotide (NAD) Axis Suppresses Atrial Fibrillation by Modulating the Calcium Handling Pathway. 2020, , 4655.

Int J Mol Sci 2021 Oct 8;22(19). Epub 2021 Oct 8.

Department of Cardiology, Institute of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.

The authors wish to make the following corrections to this paper [...].
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http://dx.doi.org/10.3390/ijms221910881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509563PMC
October 2021

Potential of Gold Nanoparticles for Noninvasive Imaging and Therapy for Vascular Inflammation.

Mol Imaging Biol 2021 Sep 27. Epub 2021 Sep 27.

Department of Cardiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.

Purpose: Macrophages contribute to the progression of vascular inflammation, making them useful targets for imaging and treatment of vascular diseases. Gold nanoparticles (GNPs) are useful as computed tomography (CT) contrast agents and light absorbers in photothermal therapy. In this study, we aimed to assess the viability of macrophages incubated with GNPs after near-infrared (NIR) laser light exposure and to evaluate the utility of intravenously injected GNPs for in vivo imaging of vascular inflammation in mice using micro-CT.

Procedures: Mouse macrophage cells (RAW 264.7) were incubated with GNPs and assessed for GNP cellular uptake and cell viability before and after exposure to NIR laser light. For in vivo imaging, macrophage-rich atherosclerotic lesions were induced by carotid ligation in hyperlipidemic and diabetic FVB mice (n = 9). Abdominal aortic aneurysms (AAAs) were created by angiotensin II infusion in ApoE-deficient mice (n = 9). These mice were scanned with a micro-CT imaging system before and after the intravenous injection of GNPs.

Results: The CT attenuation values of macrophages incubated with GNPs were significantly higher than those of cells incubated without GNPs (p < 0.04). Macrophages incubated with and without GNPs showed similar viability. The viability of macrophages incubated with GNPs (100 μg/ml or 200 μg/ml) was decreased by high-intensity NIR laser exposure but not by low-intensity NIR laser exposure. In vivo CT images showed higher CT attenuation values in diseased carotid arteries than in non-diseased contralateral arteries, although the difference was not statistically significant. The CT attenuation values of the perivascular area in AAAs of mice injected with GNPs were significantly higher than those of mice without injection (p = 0.0001).

Conclusions: Macrophages with GNPs had reduced viability upon NIR laser exposure. GNPs intravenously injected into mice accumulated in sites of vascular inflammation, allowing detection of carotid atherosclerosis and AAAs in CT imaging. Thus, GNPs have potential as multifunctional biologically compatible particles for the detection and therapy of vascular inflammation.
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http://dx.doi.org/10.1007/s11307-021-01654-5DOI Listing
September 2021

Factors Associated with Volunteer Activities and Sleep Efficiency in Older Adults with Hypertension: A Sequential Model Study.

Geriatrics (Basel) 2021 Sep 11;6(3). Epub 2021 Sep 11.

Graduate School of Comprehensive Human Sciences, Department of Human Care Science, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Ibaraki, Japan.

The purpose of this study was to examine, using a sequential model, factors associated with volunteer participation and sleep efficiency in Japanese older adults receiving treatment for hypertensive disease. A questionnaire survey was conducted to collect data on participant demographics, lifestyle, health status, and depression, and sleep activity monitors were used to objectively measure sleep status and sleep efficacy. Of the 167 respondents, the 59 being treated for hypertension were divided into two groups based on their participation in volunteering. Comparison between the groups showed significant differences in nocturnal awakening, sleep efficiency, and nap frequency. Volunteers had less nocturnal awakening, increased sleep efficiency, fewer naps, and decreased depression. Covariance structure analysis of the survey data and sleep measurements for hypertensive older adults in the volunteer group was performed by modeling the relationships between variables with a path diagram. Our model showed strong goodness of fit (χ test = 15.636, = 0.111, GFI = 0.925, AGFI = 0.842, CFI = 0.925, RMSEA = 0.099). The findings of this study suggest that older adults with hypertension who participate in volunteer activities have less nocturnal awakening, improved sleep quality, and reduced risk of depression, and provides evidence to promote social participation in volunteering among older adults with hypertension.
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http://dx.doi.org/10.3390/geriatrics6030089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482086PMC
September 2021

Right bundle branch block and risk of cardiovascular mortality: the Ibaraki Prefectural Health Study.

Heart Vessels 2021 Sep 25. Epub 2021 Sep 25.

Ibaraki Health Plaza, Ibaraki Health Service Association, Mito, Japan.

Historically, a right bundle branch block has been considered a benign finding in asymptomatic individuals. However, this conclusion is based on a few old studies with small sample sizes. We examined the association between a complete right bundle branch block (CRBBB) and subsequent cardiovascular mortality in the general population in Japan. In this large community-based cohort study, data of 90,022 individuals (mean age, 58.5 ± 10.2 years; 66.2% women) who participated in annual community-based health check-ups were assessed. Subjects were followed up from 1993 to the end of 2016. Cox proportional hazards' models and log-rank tests were used for the data analysis. CRBBB was documented in 1,344 participants (1.5%). Among all included participants, CRBBB was associated with an increased risk of cardiovascular mortality after adjustment for all potential confounders (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.06-1.38). The increased risk of cardiovascular mortality was particularly evident in women aged < 65 years (HR 2.00; 95% CI 1.34-2.98) and men aged ≥ 65 years (HR 1.28; 95% CI 1.06-1.55). CRBBB is associated with an increased risk of cardiovascular mortality in women aged < 65 years and men aged ≥ 65 years. Clinicians should be aware of the presence of CRBBB in young women and elderly men, even if they exhibit no symptoms.
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http://dx.doi.org/10.1007/s00380-021-01944-6DOI Listing
September 2021

Combined endo- and epicardial pace-mapping to localize ventricular tachycardia isthmus in ischaemic and non-ischaemic cardiomyopathy.

Europace 2021 Sep 20. Epub 2021 Sep 20.

Department of Cardiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.

Aims: A high-density pace-mapping can depict an abrupt transition in paced QRS morphology from a poor to excellent match, unmasking the critical component of ventricular tachycardia (VT) isthmus from the entrance to exit. We sought to assess pace-mapping at multiple sites within the endo- and epicardial scars to identify the VT isthmus in patients with ischaemic (ICM) and non-ischaemic cardiomyopathy (NICM).

Methods And Results: Colour-coded maps correlating to the percentage matches between 12-lead electrocardiograms during VT and pace-mapping [referred to as correlation score maps (CSMs)] were analysed. We studied 115 CSMs (80 endo- and 35 epicardial CSMs) in 37 patients (17 ICM, 20 NICM). The CSM with an abrupt change (AC) in pacemap score (AC-type) on the endocardium was more frequently observed in ICM than in NICM [11/39 (28%) vs. 1/41 (2%); P = 0.001]. Among 35 CSMs that were analysed by the combined endo- and epicardial mapping, 10 (29%) CSMs exhibited non-AC-type on the endocardium; however, AC-type was present on the opposite epicardium. Although 24 (69%) CSMs did not show AC-type on both the endocardium and epicardium, 16 of them had either an excellent (>90%) or poor (<0%) correlation score on either side, associated with isthmus exit or entrance, respectively. However, the remaining eight CSMs had neither excellent nor poor scores.

Conclusion: The CSM may provide electrophysiological information to localize the endo- and epicardial VT isthmus. The absence of AC-type CSM on the endocardium, which is frequently observed in NICM, appears to indicate the sub-epicardial or intramural course of the critical isthmus.
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http://dx.doi.org/10.1093/europace/euab245DOI Listing
September 2021

Effects of Cardiac Rehabilitation With Lumbar-Type Hybrid Assistive Limb on Muscle Strength in Patients With Chronic Heart Failure - A Randomized Controlled Trial.

Circ J 2021 Sep 11. Epub 2021 Sep 11.

Department of Cardiology, Faculty of Medicine, University of Tsukuba.

Background: Aiming to establish an effective tool in new cardiac rehabilitation programs, we investigated the use of a lumbar-type hybrid assistive limb (HAL) in patients with heart failure (HF) who had difficulty in walking at the usual speed of healthy subjects (≈80 m/min).Methods and Results:We randomly assigned 28 HF patients (age, 73.1±13.8 years) to perform a sit-to-stand exercise with or without HAL. The sit-to-stand exercise was repeated as many times as possible as cardiac rehabilitation therapy over a period of 6-10 days. We measured 5 parameters before and after the completion of cardiac rehabilitation: B-type natriuretic peptide, Short Physical Performance Battery (SPPB), 6-min walking distance (6MWD), 30-s chair-stand test (CS-30), and isometric knee extensor muscle strength. The SPPB and 6MWD were significantly improved, and the CS-30 score was somewhat improved, after the exercise therapy in both the HAL and non-HAL groups. The knee extensor muscle strength improved significantly in the HAL group (0.29±0.11 to 0.35±0.11 kgf/kg, P<0.01), but showed no change in the non-HAL group (0.35±0.11 to 0.35±0.13 kgf/kg, P=0.40).

Conclusions: The improved knee extensor muscle strength in the HAL group suggests that the lumbar-type HAL may be an effective tool for cardiac rehabilitation in HF patients with frailty, which is a predictor of poor prognosis in HF.
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http://dx.doi.org/10.1253/circj.CJ-21-0381DOI Listing
September 2021

Xanthine oxidase inhibitor febuxostat reduces atrial fibrillation susceptibility by inhibition of oxidized CaMKII in Dahl salt-sensitive rats.

Clin Sci (Lond) 2021 10;135(20):2409-2422

Department of Cardiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Oxidative stress could be a possible mechanism and a therapeutic target of atrial fibrillation (AF). However, the effects of the xanthine oxidase (XO) inhibition for AF remain to be fully elucidated. We investigated the effects of a novel XO inhibitor febuxostat on AF compared with allopurinol in hypertension rat model. Five-week-old Dahl salt-sensitive rats were fed either low-salt (LS) (0.3% NaCl) or high-salt (HS) (8% NaCl) diet. After 4 weeks of diet, HS diet rats were divided into three groups: orally administered to vehicle (HS-C), febuxostat (5 mg/kg/day) (HS-F), or allopurinol (50 mg/kg/day) (HS-A). After 4 weeks of treatment, systolic blood pressure (SBP) was significantly higher in HS-C than LS, and it was slightly but significantly decreased by treatment with each XO inhibitor. AF duration was significantly prolonged in HS-C compared with LS, and significantly suppressed in both HS-F and HS-A (LS; 5.8 ± 3.5 s, HS-C; 33.9 ± 23.7 s, HS-F; 15.0 ± 14.1 s, HS-A; 20.1 ± 11.9 s: P<0.05). Ca2+ spark frequency was obviously increased in HS-C rats and reduced in the XO inhibitor-treated rats, especially in HS-F group. Western blotting revealed that the atrial expression levels of Met281/282-oxidized Ca2+/Calmodulin-dependent kinase II (CaMKII) and Ser2814-phosphorylated ryanodine receptor 2 were significantly increased in HS-C, and those were suppressed in HS-F and HS-A. Decreased expression of gap junction protein connexin 40 in HS-C was partially restored by treatment with each XO inhibitor. In conclusion, XO inhibitor febuxostat, as well as allopurinol, could reduce hypertension-related increase in AF perpetuation by restoring Ca2+ handling and gap junction.
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http://dx.doi.org/10.1042/CS20210405DOI Listing
October 2021

Rationale and design of the HINODE study: Heart failure indication and sudden cardiac death prevention trial Japan.

J Arrhythm 2021 Aug 20;37(4):1031-1037. Epub 2021 Jul 20.

Department of Cardiology Faculty of Medicine University of Tsukuba Ibaraki Japan.

Background: Randomized trials in Western countries have provided evidence that prophylactic implantable cardioverter-defibrillator (ICD) therapy reduces mortality in heart failure (HF) patients with reduced left ventricular ejection fraction. However, the risk of life-threatening ventricular arrhythmias in Japanese HF patients sharing similar risk factors is still unknown.

Methods: The Heart Failure Indication and Sudden Cardiac Death Prevention Trial Japan trial (NCT03185832) is a prospective, multicenter registry designed to collect data on ventricular arrhythmia, HF events, and mortality in Japanese HF patients. Japanese patients with HF and 2-5 predefined risk factors who were indicated for cardiac device implantation based on European Society of Cardiology guidelines were enrolled in four treatment arms: implantable cardioverter-defibrillator (ICD), cardiac resynchronization therapy defibrillator (CRT-D), HF pacing (PA; Pacemaker and cardiac resynchronization pacemaker), and nondevice (ND) cohorts and followed for a minimum of 12 months. Since it is anticipated that some baseline patient characteristics and risk factors will differ significantly from those reported in predominantly Western populations, event rates will be compared to a propensity-matched population from the MADIT RIT trial. Primary endpoints are composite rates of first appropriately treated ventricular arrhythmias (VA) or/and life-threatening VA symptoms for the ICD and CRT-D cohorts. For nondevice and PA cohorts, the primary outcome is all-cause mortality.

Conclusions: The Heart Failure Indication and Sudden Cardiac Death Prevention Trial Japan is a large prospective multicenter registry with defined device treatment cohorts and will provide data for risk stratification for cardiovascular events in Japanese HF patients.
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http://dx.doi.org/10.1002/joa3.12577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339090PMC
August 2021

Visualization of an Accessory Pathway by 3D High-Density Mapping: A Case of Ebstein Anomaly With Atrioventricular Re-entrant Tachycardia.

CJC Open 2021 Jun 21;3(6):827-830. Epub 2021 Jan 21.

Department of Cardiology, Faculty of Medicine, University of Tsukuba, Tennodai, Tsukuba, Ibaraki, Japan.

Radiofrequency catheter ablation (RFCA) is the primary choice for treating patients with an accessory pathway and atrioventricular re-entrant tachycardia. However, using RFCA to treat a right-sided accessory pathway in a patient with Ebstein anomaly can be difficult owing to challenges in locating the electrophysiological atrioventricular groove. We report a case of atrioventricular re-entrant tachycardia in a patient with Ebstein anomaly and a right-sided accessory pathway that was successfully treated using RFCA and 3-dimensional (3D) high-density mapping. RFCA and 3D mapping may be useful in the management of such cases and may aid in improving prognoses of patients.
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http://dx.doi.org/10.1016/j.cjco.2021.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209408PMC
June 2021

Comparison of Soluble ST2, Pentraxin-3, Galectin-3, and High-Sensitivity Troponin T of Cardiovascular Outcomes in Patients With Acute Decompensated Heart Failure.

J Card Fail 2021 Nov 12;27(11):1240-1250. Epub 2021 Jun 12.

Department of Cardiology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.

Background: Data regarding a direct comparison of soluble suppression of tumorigenesis-2 (sST2), pentraxin 3 (PTX3), galectin-3 (Gal-3), and high-sensitivity troponin T of cardiovascular outcome in patients with heart failure (HF) are lacking.

Methods And Results: A total of 616 hospitalized patients with HF were evaluated prospectively. Biomarker data were obtained in the stable predischarge condition. sST2 levels were associated with age, sex, body mass index, inferior vena cava diameter, B-type natriuretic peptide (BNP), PTX3, C-reactive protein, and Gal-3 levels. During follow-up, 174 (28.4%) primary composite end points occurred, including 58 cardiovascular deaths and 116 HF rehospitalizations. sST2 predicted the end point after adjustment for 13 clinical variables (hazard ratio 1.422; 95% confidence interval [CI] 1.064 to 1.895, P = .018). The association between sST2 and the end point was no longer statistically significant after adjustment for BNP (P = .227), except in the subgroup of patients with preserved ejection fraction (hazard ratio 1.925, 95% CI 1.102-3.378, P = .021). Gal-3 and high-sensitivity troponin T predicted the risk for the end point after adjustment for age and sex, but were not significant after adjustment for clinical variables. The prognostic value of PTX3 was not observed (age and sex adjusted, P = .066).

Conclusions: This study did not show significant additional value of biomarkers to BNP for risk stratification, except sST2 in patients with preserved ejection fraction.
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http://dx.doi.org/10.1016/j.cardfail.2021.05.025DOI Listing
November 2021

study of iron oxide-calcium phosphate composite nanoparticles for delivery to atherosclerosis.

Nanotechnology 2021 May 31;32(34). Epub 2021 May 31.

Department of Cardiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.

Atherosclerosis is a macrophage-related inflammatory disease that remains a leading cause of death worldwide. Magnetic iron oxide (IO) nanocrystals are clinically used as magnetic resonance imaging contrast agents and their application as a detection agent for macrophages in arterial lesions has been studied extensively. We recently fabricated heparin-modified calcium phosphate (CaP) nanoparticles loaded with a large number of IO nanocrystals via coprecipitation from a supersaturated CaP solution supplemented with heparin and ferucarbotran (IO nanocrystals coated with carboxydextran). In this study, we further increased the content of IO nanocrystals in the heparin-modified IO-CaP composite nanoparticles by increasing the ferucarbotran concentration in the supersaturated CaP solution. The increase in nanoparticle IO content caused a decrease in particle diameter without impairing its dispersibility; the nanoparticles remained dispersed in water for up to 2 h due to electrostatic repulsion between particles due to the surface modification with heparin. The nanoparticles were more effectively taken up by murine RAW264.7 macrophages compared to free ferucarbotran without showing significant cytotoxicity. A preliminarystudy showed that the nanoparticles injected intravenously into mice delivered more IO nanocrystals to macrophage-rich carotid arterial lesions than free ferucarbotran. Our nanoparticles have potential as a delivery agent of IO nanocrystals to macrophages in arterial lesions.
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http://dx.doi.org/10.1088/1361-6528/ac007dDOI Listing
May 2021

Efficacy and Safety of SATAKE HotBalloon Catheter for Treatment of Paroxysmal Atrial Fibrillation - A Post-Marketing Surveillance Study.

Circ J 2021 07 21;85(8):1314-1320. Epub 2021 Apr 21.

Hayama Heart Center.

Background: SATAKE HotBallooncatheter (HBC) is a radiofrequency balloon catheter for the treatment of atrial fibrillation (AF), and was approved for use in Japan to treat drug-resistant paroxysmal AF in 2015. Post-marketing surveillance study was conducted by Toray Industries, Inc. to evaluate the efficacy and safety of HBC treatment in patients with paroxysmal AF in a real-world setting. This study is the first nation-wide survey of HBC treatment for paroxysmal AF in clinical practice in Japan.Methods and Results:This was a single-arm, multicenter observational study with an observation period of 48 weeks after ablation. Pulmonary vein isolation and AF non-recurrence rates were evaluated and adverse events (AEs) were observed at 46 sites in Japan. An AF event was defined as recurrence of AF or re-ablation from 12 to 48 weeks after ablation. The success rate of pulmonary vein isolation was 99.0% (486/491) for patients with AF. The cumulative AF non-recurrence rate was 94.1% at 24 weeks and 87.8% at 48 weeks. AEs were found to occur 21.5% (114/530), and ablation-related AEs were found to occur 2.6% (14/530) during the study period, with the most common being pericardial effusion (0.8%, 4/530).

Conclusions: This study demonstrates the efficacy and safety of HBC ablation in Japanese patients with recurrent symptomatic paroxysmal AF refractory to antiarrhythmic therapy.
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http://dx.doi.org/10.1253/circj.CJ-20-0883DOI Listing
July 2021

Reverse-Type Left Posterior Fascicular Ventricular Tachycardia: A New Electrocardiographic Entity.

JACC Clin Electrophysiol 2021 07 24;7(7):843-854. Epub 2021 Feb 24.

Department of Cardiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

Objectives: This study sought to demonstrate a new type of verapamil-sensitive fascicular ventricular tachycardia (VT) with a reverse circuit.

Background: Left posterior fascicular ventricular tachycardia (LPFVT) is the most common form of verapamil-sensitive fascicular VT. Reverse-type LPFVT has not been reported.

Methods: We searched for a reverse-type LPFVT among 242 patients with verapamil-sensitive VT from February 2006 to September 2019.

Results: Three patients had a reverse-type LPFVT (cycle lengths: 340, 360, and 340 ms). QRS configuration during VT was narrow (140, 150, and 140 ms) and exhibited rSr' morphology in V with an early precordial transition and inferior axis. Two of 3 patients had common-type LPFVT. During reverse-type LPFVT, the earliest ventricular activation was the left superior middle septum. Fragmented Purkinje potentials (P1) buried within the local ventricular electrogram were recorded with an activation sequence from the apex to the base and were linked to the subsequent left ventricular septal activation. After radiofrequency catheter ablation at P1 during LPFVT, the reverse-type LPFVT also became noninducible. In 1 patient with only the reverse-type LPFVT, radiofrequency catheter ablation at the earliest LV activation site suppressed VT. These findings suggest that this new type of verapamil-sensitive fascicular VT shares a re-entrant circuit with a reverse direction of common LPFVT with an intramural exit site at the superior middle septum.

Conclusions: Reverse-type LPFVT can occur. If common LPFVT exists, diastolic P1 during LPFVT can be a common target of ablation. If only reverse-LPFVT is inducible, the earliest ventricular activation site can be a target.
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http://dx.doi.org/10.1016/j.jacep.2020.11.022DOI Listing
July 2021

Long-term prognosis in patients with non-type 1 Brugada electrocardiogram: Results from a large Japanese cohort of idiopathic ventricular fibrillation.

Ann Noninvasive Electrocardiol 2021 07 19;26(4):e12831. Epub 2021 Feb 19.

Department of Internal Medicine, Cardiovascular Division, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.

Background: Brugada syndrome (BrS) is diagnosed in patients with ST-segment elevation with spontaneous, drug-induced, or fever-induced type 1 morphology. Prognosis in type 2 or 3 Brugada electrocardiogram (Br-ECG) patients remains unknown. The purpose of this study is to evaluate long-term prognosis in non-type 1 Br-ECG patients in a large Japanese cohort of idiopathic ventricular fibrillation (The Japan Idiopathic Ventricular Fibrillation Study [J-IVFS]).

Methods: From 567 patients with Br-ECG in J-IVFS, a total of 28 consecutive non-type 1 patients who underwent programmed electrical stimulation (PES) (median age: 58 years, all male, previous sustained ventricular tachyarrhythmias [VTs] 1, syncope 11, asymptomatic 16) were enrolled. Cardiac events (CEs: sudden cardiac death or sustained VT/ventricular fibrillation) during the follow-up period were examined.

Results: During a median follow-up of 136 months, four patients (14%) had CEs. None of patients with PES- have experienced CEs. There was no statistically significant clinical risk factor for the development of CEs. Using the Kaplan-Meier method, the event-free rate significantly decreased in a group with all 3 risk factors (symptom, wide QRS complex in lead V , and positive PES) (p = .01).

Conclusions: Our study revealed long-term prognosis in patients with non-type 1 Br-ECG. The combination analysis of these risk factors may be useful for the risk stratification of CEs in non-type 1 Br-ECG patients. The present study suggests that the patients with all these parameters showed high risk for CEs and need to be carefully followed.
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http://dx.doi.org/10.1111/anec.12831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293622PMC
July 2021

Programmed Death-Ligand 2 Deficiency Exacerbates Experimental Autoimmune Myocarditis in Mice.

Int J Mol Sci 2021 Jan 31;22(3). Epub 2021 Jan 31.

Department of Cardiology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.

Programmed death ligand 2 (PD-L2) is the second ligand of programmed death 1 (PD-1) protein. In autoimmune myocarditis, the protective roles of PD-1 and its first ligand programmed death ligand 1 (PD-L1) have been well documented; however, the role of PD-L2 remains unknown. In this study, we report that PD-L2 deficiency exacerbates myocardial inflammation in mice with experimental autoimmune myocarditis (EAM). EAM was established in wild-type (WT) and PD-L2-deficient mice by immunization with murine cardiac myosin peptide. We found that PD-L2-deficient mice had more serious inflammatory infiltration in the heart and a significantly higher myocarditis severity score than WT mice. PD-L2-deficient dendritic cells (DCs) enhanced CD4 T cell proliferation in the presence of T cell receptor and CD28 signaling. These data suggest that PD-L2 on DCs protects against autoreactive CD4 T cell expansion and severe inflammation in mice with EAM.
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http://dx.doi.org/10.3390/ijms22031426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866985PMC
January 2021

Optimal interruption time of dabigatran oral administration to ablation (O-A time) in patients with atrial fibrillation: Integrated analysis of 2 randomized controlled clinical trials.

J Cardiol 2021 06 25;77(6):652-659. Epub 2021 Jan 25.

Department of Cardiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. Electronic address:

Background: RE-CIRCUIT (NCT02348723) and ABRIDGE-J (UMIN000013129) are recently published randomized clinical trials showing that anticoagulation therapy with dabigatran during the periprocedural period of catheter ablation (CA) for atrial fibrillation (AF) was associated with fewer complications. However, the dabigatran administration protocols were different (uninterrupted in RE-CIRCUIT and minimally interrupted in ABRIDGE-J). The aim of this present study was to clarify the optimal interruption time of dabigatran Oral administration to Ablation (O-A time).

Methods: We conducted an integrated analysis of the 2 prospective trials. The endpoint of the study was the incidence of major bleeding events during and up to 8 weeks after CA across participants with different O-A times.

Results: The 535 patients in the dabigatran groups of the 2 trials were divided into 3 groups based on their O-A times (<8 h, n = 258; 8-24 h, n = 191; >24 h, n = 86). Major bleeding events occurred in 5 patients (1.9%) in the <8 h group, and 3 (3.5%) in the >24 h group; however, no major bleeding events occurred in the 8-24 h group (3 group-comparison, p = 0.026). No thromboembolic complication was observed in any of the 3 O-A time groups.

Conclusion: In patients undergoing CA for AF using dabigatran as a periprocedural anticoagulant, an O-A time of 8-24 h was associated with no bleeding complications. These data suggest that an O-A time of 8-24 h may be an appropriate option, especially in a low thromboembolic-risk patient.
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http://dx.doi.org/10.1016/j.jjcc.2020.12.010DOI Listing
June 2021

A New Mouse Model of Chronic Myocarditis Induced by Recombinant Bacille Calmette-Guèrin Expressing a T-Cell Epitope of Cardiac Myosin Heavy Chain-α.

Int J Mol Sci 2021 Jan 14;22(2). Epub 2021 Jan 14.

Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tsukuba 305-0843, Japan.

Dilated cardiomyopathy (DCM) is a potentially lethal disorder characterized by progressive impairment of cardiac function. Chronic myocarditis has long been hypothesized to be one of the causes of DCM. However, owing to the lack of suitable animal models of chronic myocarditis, its pathophysiology remains unclear. Here, we report a novel mouse model of chronic myocarditis induced by recombinant bacille Calmette-Guérin (rBCG) expressing a CD4 T-cell epitope of cardiac myosin heavy chain-α (rBCG-MyHCα). Mice immunized with rBCG-MyHCα developed chronic myocarditis, and echocardiography revealed dilation and impaired contraction of ventricles, similar to those observed in human DCM. In the heart, CD62LCD4 T cells were increased and produced significant amounts of IFN-γ and IL-17 in response to cardiac myosin. Adoptive transfer of CD62LCD4 T cells induced myocarditis in the recipient mice, which indicated that CD62LCD4 T cells were the effector cells in this model. rBCG-MyHCα-infected dendritic cells produced proinflammatory cytokines and induced MyHCα-specific T-cell proliferation and Th1 and Th17 polarization. This novel chronic myocarditis mouse model may allow the identification of the central pathophysiological and immunological processes involved in the progression to DCM.
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http://dx.doi.org/10.3390/ijms22020794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829923PMC
January 2021

Neutrophil Elastase Deficiency Ameliorates Myocardial Injury Post Myocardial Infarction in Mice.

Int J Mol Sci 2021 Jan 13;22(2). Epub 2021 Jan 13.

Department of Cardiology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.

Neutrophils are recruited into the heart at an early stage following a myocardial infarction (MI). These secrete several proteases, one of them being neutrophil elastase (NE), which promotes inflammatory responses in several disease models. It has been shown that there is an increase in NE activity in patients with MI; however, the role of NE in MI remains unclear. Therefore, the present study aimed to investigate the role of NE in the pathogenesis of MI in mice. NE expression peaked on day 1 in the infarcted hearts. In addition, NE deficiency improved survival and cardiac function post-MI, limiting fibrosis in the noninfarcted myocardium. Sivelestat, an NE inhibitor, also improved survival and cardiac function post-MI. Flow cytometric analysis showed that the numbers of heart-infiltrating neutrophils and inflammatory macrophages (CD11bF4/80CD206 cells) were significantly lower in NE-deficient mice than in wild-type (WT) mice. At the border zone between intact and necrotic areas, the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells was lower in NE-deficient mice than in WT mice. Western blot analyses revealed that the expression levels of insulin receptor substrate 1 and phosphorylation of Akt were significantly upregulated in NE-knockout mouse hearts, indicating that NE deficiency might improve cardiac survival by upregulating insulin/Akt signaling post-MI. Thus, NE may enhance myocardial injury by inducing an excessive inflammatory response and suppressing Akt signaling in cardiomyocytes. Inhibition of NE might serve as a novel therapeutic target in the treatment of MI.
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http://dx.doi.org/10.3390/ijms22020722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828348PMC
January 2021

An accidental sheath insertion into the internal thoracic artery during the subclavian vein puncture: bailed out by the sandwich coiling strategy.

Eur Heart J Case Rep 2020 Oct 16;4(5):1-2. Epub 2020 Aug 16.

Cardiovascular Division, Department of Cardiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.

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http://dx.doi.org/10.1093/ehjcr/ytaa278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780450PMC
October 2020

Risk stratification in asymptomatic patients with Brugada syndrome: Utility of multiple risk factor combination rather than programmed electrical stimulation.

J Cardiovasc Electrophysiol 2021 02 29;32(2):507-514. Epub 2020 Dec 29.

Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.

Background: The prognostic value of programmed electrical stimulation (PES) in Brugada syndrome (BrS) remains controversial. Asymptomatic BrS patients generally have a better prognosis than those with symptoms. The purpose of this study was to evaluate the value of nonaggressive PES with up to two extra stimuli and predict clinical factors for risk stratification in asymptomatic BrS patients.

Methods: The study enrolled 193 consecutive asymptomatic BrS patients with type 1 ECG (mean age: 50 ± 13 years, 180 males) who underwent PES using a nonaggressive uniform protocol. Cardiac events (CEs: sudden cardiac death or ventricular tachyarrhythmia) during the follow-up period were examined.

Results: During a mean follow-up of 101 ± 48 months, seven asymptomatic patients (3.6%) had a CE. The incidence of CEs was not different between patients with and without inducible ventricular tachyarrhythmia by PES (p = .51). The clinical significance of risk factor combinations, including spontaneous type 1 ECG, family history of sudden cardiac death, QRS duration in lead V , and presence of J wave, was evaluated. Using the Kaplan-Meier method according to the number of risk factors, the prevalence of CE in patients with three or four risk factors was determined to be significantly higher than in those with one risk factor (p = .02 and p = .004, respectively).

Conclusions: The present study suggests that inducibility of ventricular tachyarrhythmia does not predict future CEs in asymptomatic BrS patients. Combination analysis of the other four clinical risk parameters may be effective for risk assessment.
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http://dx.doi.org/10.1111/jce.14848DOI Listing
February 2021

Termination of long-duration ventricular fibrillation by catheter ablation.

HeartRhythm Case Rep 2020 Dec 13;6(12):955-959. Epub 2020 Oct 13.

Department of Cardiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

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http://dx.doi.org/10.1016/j.hrcr.2020.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749215PMC
December 2020

Effect of genetic polymorphism on peak propafenone concentration: no significant effect of .

Pharmacogenomics 2020 12 18;21(18):1279-1288. Epub 2020 Nov 18.

Department of Pharmaceutical Sciences, Faculty of Medicine, University of Tsukuba, Tennodai 1-1-1, Tsukuba, Ibaraki, 305 8575, Japan.

The study aims to investigate the clinical implication of nonfunctional poor metabolizer (PM) alleles and intermediate metabolizer (IM) alleles of , including the allele which shows substrate-dependent decrease in enzymatic activity, in antiarrhythmic therapy using propafenone. We examined serum propafenone concentrations and metabolic ratio, which was expressed as serum concentrations of propafenone to 5-hydroxypropafenone, in 66 Japanese patients with tachyarrhythmias. The peak propafenone concentration and metabolic ratio in PM allele carriers were higher than those in extensive metabolizer (EM)/EM, EM/IM and IM/IM genotype groups. Results suggest that PM alleles affect peak propafenone concentration, but the IM allele has no clinical implication in propafenone dosing.
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http://dx.doi.org/10.2217/pgs-2020-0105DOI Listing
December 2020

Utility of Circadian Variability Patterns in Differentiating Origins of Premature Ventricular Complexes.

J Interv Cardiol 2020 30;2020:7417912. Epub 2020 Oct 30.

Department of Cardiology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Background: Premature ventricular complexes (PVCs) exhibit circadian fluctuation. We determine if PVCs of different origin exhibit specific circadian patterns.

Methods: We analyzed Holter recordings from patients with monomorphic PVCs who underwent catheter ablation. PVC circadian patterns were classified as fast-heart rate- (HR-) dependent (F-PVC), slow-HR-dependent (S-PVC), or HR-independent (I-PVC). PVC origins were determined intraprocedurally.

Results: In a retrospective cohort of 407 patients, F-PVC and S-PVC typically exhibited diurnal and nocturnal predominance, respectively. Despite decreased circadian fluctuation, I-PVC generally had heavier nocturnal than diurnal burden. PVCs of left anterior fascicle origin were predominantly S-PVC, while those of posterior hemibranch origin were mostly F-PVC. PVCs originating from the aortic sinus of Valsalva (ASV) were predominantly I-PVC, while most PVCs arising from the left ventricular outflow tract (LVOT) were F-PVC. Using a diurnal/nocturnal PVC burden ratio of 0.92 as the cutoff value to distinguish LVOT from ASV origin achieved 97% sensitivity and, as further verification, an accuracy of 89% (16/18) in a prospective cohort of patients with PVCs originating from either ASV or LVOT. In contrast, PVCs originating from right ventricles, such as right ventricular outflow tract, did not show distinct circadian patterns.

Conclusions: The circadian patterns exhibit origin specificity for PVCs arising from left ventricles. An analysis of Holter monitoring provides useful information on PVC localization in ablation procedure planning.
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http://dx.doi.org/10.1155/2020/7417912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647775PMC
April 2021

MAIR-II deficiency ameliorates cardiac remodelling post-myocardial infarction by suppressing TLR9-mediated macrophage activation.

J Cell Mol Med 2020 12 2;24(24):14481-14490. Epub 2020 Nov 2.

Department of Cardiology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.

Macrophages are fundamental components of inflammation in post-myocardial infarction (MI) and contribute to adverse cardiac remodelling and heart failure. However, the regulatory mechanisms in macrophage activation have not been fully elucidated. Previous studies showed that myeloid-associated immunoglobulin-like receptor II (MAIR-II) is involved in inflammatory responses in macrophages. However, its role in MI is unknown. Thus, this study aimed to determine a novel role and mechanism of MAIR-II in MI. We first identified that MAIR-II-positive myeloid cells were abundant from post-MI days 3 to 5 in infarcted hearts of C57BL/6J (WT) mice induced by permanent left coronary artery ligation. Compared to WT, MAIR-II-deficient (Cd300c2 ) mice had longer survival, ameliorated cardiac remodelling, improved cardiac function and smaller infarct sizes. Moreover, we detected lower pro-inflammatory cytokine and fibrotic gene expressions in Cd300c2 -infarcted hearts. These mice also had less infiltrating pro-inflammatory macrophages following MI. To elucidate a novel molecular mechanism of MAIR-II, we considered macrophage activation by Toll-like receptor (TLR) 9-mediated inflammation. In vitro, we observed that Cd300c2 bone marrow-derived macrophages stimulated by a TLR9 agonist expressed less pro-inflammatory cytokines compared to WT. In conclusion, MAIR-II may enhance inflammation via TLR9-mediated macrophage activation in MI, leading to adverse cardiac remodelling and poor prognosis.
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http://dx.doi.org/10.1111/jcmm.16070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753988PMC
December 2020

The Usefulness and Limitations of Impedance Cardiography for Cardiac Resynchronization Therapy Device Optimization.

Int Heart J 2020 ;61(5):896-904

Department of Cardiology, Faculty of Medicine, University of Tsukuba.

Identifying the optimal atrioventricular (AV) or interventricular (VV) delay is beneficial for patients using cardiac resynchronization therapy (CRT) devices. Ultrasonic echocardiography (UCG) has been the most commonly used method; however, it requires high technical knowledge. Impedance cardiography (ICG) can calculate stroke volume by measuring changes in transthoracic electric impedance. This study sought to assess the clinical utility of ICG in comparison with that of UCG for the optimization of CRT devices.Patients who underwent CRT device implantation were retrospectively analyzed. One week after implantation, optimization of AV delay (AVD) was performed in every patient with ICG (AVD-ICG) and UCG (AVD-UCG). VV delay (VVD) was then determined according to the optimal AVD using these two methods.Forty-two patients were enrolled. Average AVD-ICG was significantly shorter than AVD-UCG (128 ± 49 versus 146 ± 41 milliseconds, P = 0.018). Five patients (12%) had the same optimized AVD with two methods, and the difference between AVD-ICG and AVD-UCG was ≤ 20 milliseconds in 19 patients (45%). In the multivariate analysis, the presence of postoperative mitral regurgitation (MR) was an independent predictor of AVD-ICG/AVD-UCG mismatch, defined as a difference over 20 milliseconds (odds ratio = 10.71; 95% confidence interval = 1.72 to 66.72; P = 0.018). The results of optimized VVD were similar using both methods.ICG might be a promising tool for the rapid optimization of CRT devices. However, in patients with moderate-to-severe MR, ICG may not be able to optimize AVD.
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http://dx.doi.org/10.1536/ihj.19-620DOI Listing
October 2020

Predictors of increase in pacing threshold after transcatheter pacing system implantation due to micro-dislodgement.

Pacing Clin Electrophysiol 2020 11 3;43(11):1351-1357. Epub 2020 Oct 3.

Department of Cardiology, Mito Saiseikai General Hospital, Mito, Japan.

Background: Achieving a favorable pacing threshold with a Micra transcatheter pacing system (Micra-TPS) is needed to reduce battery depletion. In some cases, the threshold increases shortly after the device is implanted, and a higher pacing threshold may be required. This study aims to identify the causes and predictors of the increase in pacing threshold observed shortly after Micra-TPS implantation.

Methods: The study included 64 consecutive patients who underwent Micra-TPS implantation between 2017 and 2020. The patients were divided into two groups depending on their pacing threshold: the increased pacing threshold (IPT) group (threshold increased by ≥0.5 V/0.24 ms within 1 month of implantation) and the stable pacing threshold (SPT) group.

Results: Excluding four patients who could not be followed up, of the 60 remaining patients, nine (15%) were in the IPT group and 51 (85%) were in the SPT group. The IPT group had significantly lower implant impedance values and higher implant thresholds than the SPT group (582 ± 59 vs 755 ± 167 Ω [P < .001] and 1.29 ± 0.87 vs 0.71 ± 0.40 V/0.24 ms [P = .014]). Implant impedance and threshold may serve as predictors of a threshold increase after implantation (area under the curve: 0.737-0.943 and 0.586-0.926, respectively).

Conclusions: An IPT was noted shortly after Micra-TPS implantation owing to micro-dislodgement because of insufficient anchoring of the device to the myocardium. Impedance >660 Ω and threshold <1.0 V/0.24 ms may predict an increase in pacing threshold.
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http://dx.doi.org/10.1111/pace.14080DOI Listing
November 2020
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