Publications by authors named "Masayuki Takamura"

162 Publications

Finding Clues to Protect Against Coronary Atherosclerosis via Traditional Risk Factors.

J Atheroscler Thromb 2022 Jul 28. Epub 2022 Jul 28.

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences.

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http://dx.doi.org/10.5551/jat.ED211DOI Listing
July 2022

Clinical Characteristics, Outcomes, and Risk Factors for Adverse Events in Elderly and Non-Elderly Japanese Patients With Non-Valvular Atrial Fibrillation - Competing Risk Analysis From the Hokuriku-Plus AF Registry.

Circ Rep 2022 Jul 15;4(7):298-307. Epub 2022 Jun 15.

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences Kanazawa Japan.

Few studies in Japan have reported on follow-up data regarding the clinical course and risk factors for adverse outcomes in elderly patients with non-valvular atrial fibrillation (NVAF), vs. younger patients, when considering the competing risk of death. We prospectively studied 1,328 patients with NVAF (965 men; mean [±SD] age 72.4±9.7 years) from the Hokuriku-Plus AF Registry with a median follow-up of 5.0 years (interquartile range 3.5-5.3 years) and evaluated the incidence of thromboembolism or major bleeding in elderly (age ≥75 years; n=595) and non-elderly (age <75 years; n=733) patients. Analysis using the Gray method showed no significant difference in the incidence of thromboembolism; however, the incidence of major bleeding was significantly higher in the elderly than non-elderly group. The Fine-Gray model, after adjustment for age and sex in the elderly group, showed that age (hazard ratio [HR] 1.08; 95% confidence interval [CI] 1.02-1.13; P=0.004) and warfarin use (HR 1.87; 95% CI 1.12-3.14; P=0.02) were significantly associated with major bleeding. In the elderly group, those using warfarin had a higher incidence of thromboembolism and major bleeding than those using direct oral anticoagulants (DOACs). The efficacy and safety of DOACs were remarkable in elderly compared with non-elderly patients with NVAF considering the competing risk of death. DOACs may be a favorable choice in elderly patients with NVAF.
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http://dx.doi.org/10.1253/circrep.CR-22-0012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257453PMC
July 2022

Ablation index-guided high-power vs. moderate-power cavotricuspid isthmus ablation.

Heart Vessels 2022 Jul 19. Epub 2022 Jul 19.

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa, 920-8641, Japan.

Ablation index (AI)-guided ablation is useful for pulmonary vein isolation (PVI) and cavotricuspid isthmus (CTI) ablation. However, the impact of radiofrequency (RF) application power on CTI ablation with a fixed target AI remains unclear. One-hundred-thirty drug-refractory atrial fibrillation and/or atrial flutter patients who underwent AI-guided CTI ablation with or without PVI between July 2020 and August 2021 were randomly assigned to high-power (45 W) and moderate-power (35 W) groups. We performed CTI ablation with the same target AI value in both groups: 500 for the anterior 1/3 segments and 450 for the posterior 2/3 segments. In total, first-pass conduction block of the CTI was obtained in 111 patients (85.4%), with 7 patients (5.4%) showing CTI reconnection. The rate of first-pass conduction block was significantly higher in the 45 W group (61/65, 93.8%) than in the 35 W group (50/65, 76.9%, P = 0.01). CTI ablation and CTI fluoroscopy time were significantly shorter in the 45 W group than in the 35 W group (CTI ablation time: 192.3 ± 84.8 vs. 319.8 ± 171.4 s, P < 0.0001; CTI fluoroscopy time: 125.2 ± 122.4 vs. 171.2 ± 124.0 s, P = 0.039). Although there was no significant difference, steam pops were identified in two patients from the 45 W group at the anterior segment of the CTI. The 45 W ablation strategy was faster and provided a higher probability of first-pass conduction block than the 35 W ablation strategy for CTI ablation with a fixed AI target.
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http://dx.doi.org/10.1007/s00380-022-02125-9DOI Listing
July 2022

Therapeutic angiogenesis for patients with no-option critical limb ischemia by adipose-derived regenerative cells: TACT-ADRC multicenter trial.

Angiogenesis 2022 Jul 8. Epub 2022 Jul 8.

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

Background: Patients with critical limb ischemia (CLI) still have a high rate of lower limb amputation, which is associated with not only a decrease in quality of life but also poor life prognosis. Implantation of adipose-derived regenerative cells (ADRCs) has an angiogenic potential for patients with limb ischemia.

Objectives: We investigated safety, feasibility, and efficacy of therapeutic angiogenesis by cell transplantation (TACT) of ADRCs for those patients in multicenter clinical trial in Japan.

Methods: The TACT-ADRC multicenter trial is a prospective, interventional, open-labeled study. Patients with CLI (Fontaine class III-IV) who have no other option for standard revascularization therapy were enrolled in this study. Thirty-four target ischemic limbs of 29 patients were received freshly isolated autologous ADRCs implantation.

Results: The overall survival rate at a post-operative period and at 6 months follow-up was 100% at any time points. As a primary endpoint for efficacy evaluation, 32 limbs out of 34 (94.1%) were free from major amputation for 6 months. Numerical rating scale (from 6 to 1) as QOL score, ulcer size (from 317 mm at to 109 mm), and 6-min walking distance (from 255 to 369 m) improved in 90.6%, 83.3%, and 72.2% patients, respectively.

Conclusions: Implantation of autologous ADRCs could be safe and effective for the achievement of therapeutic angiogenesis in the multicenter settings, as a result in no major adverse event, optimal survival rate, and limb salvage for patients with no-conventional option against critical limb ischemia. TRN: jRCTb040190118; Date: Nov. 24th, 2015.
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http://dx.doi.org/10.1007/s10456-022-09844-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263817PMC
July 2022

Effect of pulmonary vein isolation on the relationship between left atrial reverse remodeling and sympathetic nerve activity in patients with atrial fibrillation.

Clin Auton Res 2022 Jun 23. Epub 2022 Jun 23.

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences Kanazawa, Kanazawa, Japan.

Purpose: Catheter ablation (CA) to isolate the pulmonary vein, which is an established treatment for atrial fibrillation (AF), is associated with left atrium reverse remodeling (LARR). The intrinsic cardiac autonomic nervous system includes the ganglion plexi adjacent to the pulmonary vein in the left atrium (LA). However, little is known about the effect of CA on the relationship between LARR and sympathetic nerve activity in patients with AF.

Methods: This study enrolled 22 AF patients with a normal left ventricular ejection fraction (LVEF) aged 64.6 ± 12.9 years who were scheduled for CA. Sympathetic nerve activity was evaluated by direct recording of muscle sympathetic nerve activity (MSNA) before and 12 weeks after CA. Blood pressure, heart rate (HR), HR variability, and echocardiography were also measured.

Results: The heart rate increased significantly after CA (63 ± 10.9 vs. 70.6 ± 7.7 beats/min, p < 0.01), but blood pressure did not change. A high frequency (HF) and low frequency (LF) of HR variability decreased significantly after ablation, but no significant change in LF/HF was observed. CA significantly decreased MSNA (38.9 ± 9.9 vs. 28 ± 9.1 bursts/min, p < 0.01). Moreover, regression analysis revealed a positive correlation between the percentage change in MSNA and the LA volume index (r = 0.442, p < 0.05).

Conclusions: Our results show that CA for AF reduced MSNA and the decrease was associated with the LA volume index in AF patients with a normal LVEF. These findings suggest that LARR induced by CA for AF decrease sympathetic nerve activity.
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http://dx.doi.org/10.1007/s10286-022-00873-2DOI Listing
June 2022

Children with Severe Hypercholesterolemia Caused by a Pathogenic Mutation in ABCG5.

Intern Med 2022 Jun 14. Epub 2022 Jun 14.

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

We herein present a case series of hypercholesterolemia caused by a pathogenic mutation in the ATP-binding cassette sub-family G member 5 (ABCG5). Three unrelated infantile patients who were breastfed and had extremely elevated low-density lipoprotein (LDL) cholesterol levels were referred to our hospital. Their LDL cholesterol levels decreased significantly after weaning. Panel sequencing revealed a pathogenic mutation in ABCG5 in each patient. An 8-year-old girl was also referred due to suspected Familial hypercholesterolemia. Panel sequencing revealed a pathogenic mutation in ABCG5. A cholesterol-reduced diet alone significantly reduced the LDL cholesterol levels. Moreover, the administration of ezetimibe was found to be beneficial.
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http://dx.doi.org/10.2169/internalmedicine.0050-22DOI Listing
June 2022

Impact of hyperuricemia on coronary blood flow and in-hospital mortality in patients with acute myocardial infarction undergoing percutaneous coronary intervention.

J Cardiol 2022 Sep 17;80(3):268-274. Epub 2022 May 17.

Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Japan.

Background: Although serum uric acid (UA) is considered as a risk factor for cardiovascular disease, few data exist regarding the relationship between hyperuricemia, coronary blood flow, and subsequent outcome in patients with acute myocardial infarction (AMI). The purpose of our study is to assess whether hyperuricemia is associated with suboptimal coronary flow and increased risk of mortality in patients with AMI after percutaneous coronary intervention (PCI).

Methods: Using the Rural AMI registry data, 989 consecutive patients with AMI who underwent emergent PCI and had UA measurement at admission were analyzed. We defined hyperuricemia as serum UA ≥7.0 mg/dL in men and ≥ 6.0 mg/dL in women. The primary endpoint was suboptimal coronary flow, defined as post PCI Thrombosis In Myocardial Infarction flow grade ≤ 2. The secondary outcome was in-hospital mortality.

Results: Hyperuricemia was found in 249 (25.2%) patients. Patients with hyperuricemia were more often complicated with cardiogenic shock compared with those without (16.9% vs. 7.4%, p < 0.001). In addition, the median high-sensitivity C-reactive protein was significantly higher in patients with hyperuricemia (0.18 mg/dL; IQR, 0.09-0.71 mg/dL) than in those without (0.14 mg/dL; IQR, 0.07-0.41 mg/dL, p < 0.05). Under these conditions, the prevalence of suboptimal coronary flow after PCI (17.3% vs. 10.1%, p < 0.05) and in-hospital mortality (10.8% vs. 3.6%, p < 0.001) were significantly higher in patients with hyperuricemia compared with those without. Multivariable logistic regression analysis revealed that hyperuricemia was significantly associated with suboptimal coronary flow [odds ratio (OR), 1.60; 95% confidence interval (CI), 1.02-2.49; p < 0.05] and in-hospital mortality (OR, 2.08; 95% CI, 1.05-4.12; p < 0.05).

Conclusions: Assessment of serum UA upon admission provides useful information for predicting suboptimal coronary flow and in-hospital mortality in patients with AMI undergoing PCI.
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http://dx.doi.org/10.1016/j.jjcc.2022.04.009DOI Listing
September 2022

Relationships between muscle sympathetic nerve activity and novel indices of arterial stiffness using single oscillometric cuff in patients with hypertension.

Physiol Rep 2022 05;10(10):e15270

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

The arterial velocity pulse index (AVI) and arterial pressure-volume index (API) have been proposed as new arterial stiffness indices that can be measured using an oscillometric cuff. Sympathetic nerve activity (SNA) contributes to arterial stiffness via increasing vascular smooth muscle tone. However, the associations between SNA and the AVI or API are not understood. The purpose of this study was to evaluate the relationships between muscle sympathetic nerve activity (MSNA) and the AVI or API in healthy individuals and patients with hypertension (HT). Forty healthy individuals (40.1 ± 15.2 years, 8 females) (healthy group) and 40 patients with HT (60.2 ± 13.6, 18 females) (HT group) were included in this study. The AVI, API, MSNA, beat-by-beat blood pressure, and heart rate were recorded simultaneously. The AVI and API were higher in the HT group than in the healthy group (AVI, 26.1 ± 7.6 vs. 16.5 ± 4.0, p < 0.001; API, 31.2 ± 8.6 vs. 25.5 ± 7.2, p = 0.002). MSNA in the HT group was also higher than in the healthy group (p < 0.001). MSNA was correlated with the AVI, but not with the API, in both the healthy group (R = 0.52, p = 0.001) and HT group (R = 0.57, p < 0.001). MSNA was independently correlated with the AVI in multivariate analysis (ß = 0.34, p = 0.001). In conclusion, AVI, obtained by a simple and less user-dependent method, was related to the MSNA in healthy individuals and patients with HT.
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http://dx.doi.org/10.14814/phy2.15270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118049PMC
May 2022

The Association Between Serum Uric Acid and Mortality in Patients with Acute Coronary Syndrome After Percutaneous Coronary Intervention.

Int Heart J 2022 May 14;63(3):447-453. Epub 2022 May 14.

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences.

This study aims to explore the associations between uric acid (UA) and long-term outcomes among patients with acute coronary syndrome (ACS). A total of 1068 consecutive patients with ACS who underwent percutaneous coronary intervention (PCI) were analyzed retrospectively. The patients were divided into 3 groups based on the levels of serum UA upon admission (bottom quintile, middle 3 quintiles, and top quintile). The primary endpoint was all-cause mortality. The patients in the higher UA groups were associated with younger age (71 ± 11 versus 68 ± 12 versus 67 ± 14 years; P < 0.05) and were more likely to be male (57.6 versus 76.9 versus 84.7%; P < 0.001). Furthermore, these patients had lower estimated glomerular filtration rates (83 ± 27 versus 74 ± 23 versus 59 ± 24 mL/minute/1.73 m; P < 0.001) and lower left ventricular ejection fractions (58 ± 14 versus 57 ± 14 versus 53 ± 15%; P < 0.001). During the median 4-year follow-up, there were 158 incidents of all-cause death. Patients in the top quintile, followed by patients in the bottom quintile, had greater all-cause mortality compared with patients in the middle quintile (16.5 versus 11.4 versus 23.8%; P < 0.001). When the middle of the 3 quintiles was assigned as the reference group, the adjusted hazard ratios for all-cause mortality for the top and bottom quintiles were 1.72 (95% confidence interval [CI] 1.16-2.53, P < 0.05) and 1.57 (95% CI 1.03-2.36, P < 0.05), respectively. These results demonstrate that UA levels upon admission in patients with ACS who underwent PCI exhibited a 'J-shaped' association with all-cause mortality.
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http://dx.doi.org/10.1536/ihj.21-764DOI Listing
May 2022

Effects of Different Types of Pathogenic Variants on Phenotypes of Familial Hypercholesterolemia.

Front Genet 2022 11;13:872056. Epub 2022 Apr 11.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.

It has been shown that pathogenic variants are associated with poor clinical outcomes in patients with familial hypercholesterolemia (FH). However, data on the effect of different types of pathogenic variants on FH phenotype is limited. We retrospectively investigated the associations between genotypes and phenotypes, including low-density lipoprotein (LDL) cholesterol level and the occurrence of major adverse cardiac events (MACEs), defined as cardiovascular death, myocardial infarction, unstable angina, or coronary artery revascularization, in patients with FH (N = 1,050, male/female = 490/560). Based on genotype, the patients were divided into the following three groups: patients without pathogenic variants, patients with missense variants, and patients with protein-truncating variants (PTVs). Cox proportional hazard model was used to identify the factors associated with MACEs. The median follow-up duration was 12.6 years (interquartile range = 9.5-17.9 years). There were 665 patients with FH-mutation (277 patients with missense variants and 388 patients with PTVs) and 385 patients without FH-mutation. Over the follow-up duration, 175 MACEs were observed. We identified 89 different pathogenic variants in the 665 patients with FH. LDL cholesterol level was found to be significantly higher in patients with PTVs (256 mg/dl) than in patients with missense variants (236 mg/dl) and patients without pathogenic variants (216 mg/dl). It was also found that PTVs and missense variants are significantly associated with MACEs (hazard ratio [HR] = 1.58, 95% confidence interval [CI] = 1.08-2.08, = 0.0033 and HR = 3.24, 95% CI = 2.12-4.40, = 3.9 × 10, respectively), independent of classical risk factors. Pathogenic variants, especially PTVs, are significantly associated with poor outcomes in patients with FH. Genetic testing is useful for the diagnosis and risk stratification of patients with FH.
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http://dx.doi.org/10.3389/fgene.2022.872056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9035489PMC
April 2022

Case Report: Myocarditis Associated With COVID-19 mRNA Vaccination Following Myocarditis Associated With .

Front Cardiovasc Med 2022 18;9:837759. Epub 2022 Mar 18.

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

We herein present our experience with a case involving a 17-year-old Japanese boy suffering from acute myocarditis after his second coronavirus disease-2019 (COVID-19) messenger RNA (mRNA) vaccine shot. The patients had a history of myocarditis associated with 3 years prior. This has been the first-ever documented case of myocarditis associated with COVID-19 mRNA vaccination in a patient with a history of myocarditis. We present a series of images and blood biomarkers for different types of myocarditis that developed in this single patient.
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http://dx.doi.org/10.3389/fcvm.2022.837759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971558PMC
March 2022

A Case of Pulmonary Hypertension in a 67-Year-Old Woman with Thiamine Deficiency Following Partial Gastrectomy and Exacerbated by Diuretics.

Am J Case Rep 2022 Mar 17;23:e935308. Epub 2022 Mar 17.

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.

BACKGROUND Thiamine deficiency often occurs in patients with alcohol abuse and unbalanced diets. However, gastric surgery and/or use of diuretics can also cause this situation. Importantly, thiamine deficiency can cause pulmonary hypertension, which is completely reversible. This report is of a case of a 67-year-old woman who presented with pulmonary hypertension and thiamine deficiency following partial gastrectomy and exacerbated by diuretics. CASE REPORT A 67-year-old woman with histories of partial gastrectomy because of non-Hodgkin lymphoma (at age 36 years) and sigmoid colectomy because of colon cancer (at age 58 years) presented with bilateral leg edema and dyspnea on exertion. Electrocardiography and right heart catheterization revealed pulmonary hypertension. Despite diuretic administration (initially indapamide, then changed to torsemide), the symptoms gradually worsened. Although she was neither an alcohol drinker nor a fussy eater, we found that her blood thiamine concentration was extremely low. We diagnosed her as having thiamine deficiency caused by gastrectomy and administered diuretics. After intravenous thiamine administration, her symptoms showed immediate improvement, associated with the normalization of the pulmonary hypertension. After detailed analysis of the cause of her pulmonary hypertension, including Swan-Ganz catheterization and echocardiography, we concluded that her pulmonary hypertension was caused by thiamine deficiency following partial gastrectomy and exacerbated by diuretics. CONCLUSIONS This case highlights the importance of recognizing that thiamine deficiency can be a cause of pulmonary hypertension, and that thiamine deficiency can be associated with gastrectomy and the use of diuretics.
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http://dx.doi.org/10.12659/AJCR.935308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8938710PMC
March 2022

Clinical and genetic features of sitosterolemia in Japan.

Clin Chim Acta 2022 May 4;530:39-44. Epub 2022 Mar 4.

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Japan.

Background And Aim: Clinical manifestations and genetic backgrounds of Japanese patients with sitosterolemia have been unclear.

Materials And Methods: We searched PubMed for studies using the keywords "sitosterolemia" or "phytosterolemia" and "Japan". Moreover, we added information from the members of the Committee on Primary Dyslipidemia under the Research Program on Rare and Intractable Disease of the Ministry of Health, Labour and Welfare (MHLW) of Japan.

Results: We identified 36 patients with sitosterolemia caused by biallelic pathogenic mutations in the ATP-binding cassette subfamily G member 5 (ABCG5) or ATP-binding cassette subfamily G member 8 (ABCG8) from 31 families in Japan. The diagnosed age ranged from 0 to 64 years (median 13 years). The median sitosterol and LDL cholesterol levels were 100 μg/ml (IQR: 50-183), and 193 mg/dl (IQR: 108-295), respectively. All the patients exhibited cutaneous and/or tendon xanthomas, up to 9 (25%) patients exhibited premature coronary artery disease, 5 (16%) patients exhibited arthritis, and 8 (22%) patients exhibited blood abnormalities. Ezetimibe was administered to all the patients, including infantile cases, while statins, colestimide, evolocumab, probucol, and LDL apheresis were also used.

Conclusion: We are providing a demographic overview of the clinical and genetic backgrounds of Japanese patients with sitosterolemia.
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http://dx.doi.org/10.1016/j.cca.2022.02.021DOI Listing
May 2022

Elevated muscle sympathetic activity in former smokers with heart failure.

Clin Auton Res 2022 04 19;32(2):151-154. Epub 2022 Feb 19.

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

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http://dx.doi.org/10.1007/s10286-022-00857-2DOI Listing
April 2022

Eggplant-Like Coronary Aneurysm With Massive Thrombus.

Circ Rep 2022 Feb 18;4(2):107-108. Epub 2022 Jan 18.

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences Kanazawa Japan.

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http://dx.doi.org/10.1253/circrep.CR-21-0149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8811225PMC
February 2022

Individualized Treatment for Patients With Familial Hypercholesterolemia.

J Lipid Atheroscler 2022 Jan 3;11(1):39-54. Epub 2022 Jan 3.

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

Familial hypercholesterolemia (FH) is one of the most common and, therefore, important inherited disorders in preventive cardiology. This disease is mainly caused by a single pathogenic mutation in the low-density lipoprotein receptor or its associated genes. Moreover, it is correlated with a high risk of cardiovascular disease. However, the phenotype severity even in this monogenic disease significantly varies. Thus, the current study aimed to describe FH and its importance and the factors (inherited and acquired) contributing to differences in phenotype severity. Different lipid-modification therapies according to these factors can lead to individualized treatments, which are also essential in the general populations.
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http://dx.doi.org/10.12997/jla.2022.11.1.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8792816PMC
January 2022

The Effect of Diet on Cardiovascular Disease, Heart Disease, and Blood Vessels.

Nutrients 2022 Jan 7;14(2). Epub 2022 Jan 7.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-1192, Japan.

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http://dx.doi.org/10.3390/nu14020246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8780028PMC
January 2022

Precaval bundle re-entry atrial tachycardia: a variant of upper loop re-entry.

J Interv Card Electrophysiol 2022 04 3;63(3):737-738. Epub 2022 Jan 3.

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.

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http://dx.doi.org/10.1007/s10840-021-01105-9DOI Listing
April 2022

Characterization of adipose tissue-derived stromal cells of mice with nonalcoholic fatty liver disease and their use for liver repair.

Regen Ther 2021 Dec 3;18:497-507. Epub 2021 Dec 3.

Department of Gastroenterology, Kanazawa University Hospital, Kanazawa, Japan.

Introduction: Freshly isolated uncultured adipose tissue-derived stromal cells (u-ADSCs), containing miscellaneous cells like the relatively abundant mesenchymal stem cells, are attractive for repair and regenerative therapy. However, the detailed characteristics and therapeutic efficacy of u-ADSCs obtained from disease-affected hosts are unknown. We compared the properties of u-ADSCs obtained from wild-type mice and from a mouse model of non-alcoholic steatohepatitis (NASH).

Methods: The NASH model was established by feeding C57BL/6J mice an atherogenic high-fat diet for 4 (NASH (4w)) or 12 weeks (NASH (12w)), followed by the isolation and characterization of u-ADSCs. Wild-type u-ADSCs or NASH-derived u-ADSCs were administered to mice with NASH cirrhosis, followed by analyses of hepatic inflammatory cells, antigen profiles, fibrosis, and gene expression.

Results: Wild-type u-ADSCs and NASH-derived u-ADSCs did not show marked differences in surface antigen profiles. In NASH (4w) u-ADSCs, but not NASH (12w) u-ADSCs, the frequencies of the leukocyte markers CD11b, CD45, and CD44 were elevated; furthermore, we observed an increase in the M1/M2 macrophage ratio only in NASH (12w) u-ADSCs. Only in NASH-4w u-ADSCs, the expression levels cell cycle-related genes were higher than those in u-ADSCs. Wild-type u-ADSCs administered to mice with NASH-related cirrhosis decreased the infiltration of CD11b+, F4/80+, and Gr-1+ inflammatory cells, ameliorated fibrosis, and had a restorative effect on liver tissues, as determined by gene expression profiles and the NAFLD activity score. The therapeutic effects of NASH (4w) u-ADSCs and NASH (12w) u-ADSCs on NASH-related cirrhosis were highly similar to the effect of wild-type u-ADSCs, including reductions in inflammation and fibrosis.

Conclusions: NASH-derived u-ADSCs, similar to wild-type u-ADSCs, are applicable for reparative and regenerative therapy in mice with NASH.
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http://dx.doi.org/10.1016/j.reth.2021.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649123PMC
December 2021

Genetic mutations, regression of Achilles tendon thickness, and cardiovascular events among patients with familial hypercholesterolemia.

Atherosclerosis 2022 01 2;340:28-34. Epub 2021 Dec 2.

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

Background And Aims: Achilles tendon thickness (ATT) can be regressed through LDL-lowering in patients with familial hypercholesterolemia (FH). We aimed to determine factors associated with regression of ATT and its role in development of major adverse cardiovascular events (MACE).

Methods: Patients with clinically diagnosed FH (N = 1,050, male/female = 490/560) were retrospectively assessed. FH-related gene mutations and ATT data using X-ray were collected. Multivariable linear regression analysis was exploited to test the factors associated with deterioration of ATT. Cox proportional hazards models were used to assess factors associated with MACE, including cardiovascular death and acute coronary events.

Results: The median follow-up period was 12.6 years. FH-linked mutations were identified in 777 patients. During the follow-up period, 113 MACEs were observed, and median ATT was regressed from 8.7 to 8.5 mm. We found that there was more significant positive correlation between cholesterol-year score and ATT among patients with FH-related gene mutation (p < 2.2 × 10; Spearman's r = 0.42). Multivariable linear regression analyses revealed that age (standardized coefficients [SCs] = 0.307, 95% confidence interval [CI] = 0.241-0.373), hypertension (SCs = 0.069, 95%CI = 0.001-0.138), and diabetes (SCs = 0.059, 95% CI = 0.003-0.115) were positively correlated with changes in ATT (progression). Baseline ATT (SCs = -0.474, 95%CI = -0.535-0.413) and FH-related mutations (SCs = -0.058, 95%CI = -0.091-0.024) were negatively correlated with changes in ATT (regression). Considering this confounding factors, regression of ATT was significantly associated with reduced MACE (hazard ratio [HR] = 0.67, 95%CI = 0.51-0.89, per 1.0 mm).

Conclusions: Assessed ATT condition and presence of FH-linked gene mutations represent diagnostic values and risk stratification information among patients with FH.
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http://dx.doi.org/10.1016/j.atherosclerosis.2021.11.031DOI Listing
January 2022

Hemodynamic Stratification of the Pulmonary Vasculature in Patients Undergoing Transcatheter Aortic Valve Replacement.

Circ J 2022 02 9;86(3):391-392. Epub 2021 Nov 9.

Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kanazawa University.

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http://dx.doi.org/10.1253/circj.CJ-21-0820DOI Listing
February 2022

Different Responses of Muscle Sympathetic Nerve Activity to Dapagliflozin Between Patients With Type 2 Diabetes With and Without Heart Failure.

J Am Heart Assoc 2021 11 30;10(22):e022637. Epub 2021 Oct 30.

Department of Cardiovascular Medicine Kanazawa University Graduate School of Medical Sciences Kanazawa Japan.

Background Sodium-glucose cotransporter 2 inhibitors improve cardiovascular outcomes in patients with diabetes with and without heart failure (HF). However, their influence on sympathetic nerve activity (SNA) remains unclear. The purpose of this study was to evaluate the effect of sodium-glucose cotransporter 2 inhibitors on SNA and compare the responses of SNA to sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes with and without HF. Methods and Results Eighteen patients with type 2 diabetes, 10 with HF (65.4±3.68 years) and 8 without HF (63.3±3.62 years), were included. Muscle SNA (MSNA), heart rate, and blood pressure were recorded before and 12 weeks after administration of dapagliflozin (5 mg/day). Sympathetic and cardiovagal baroreflex sensitivity were simultaneously calculated. Brain natriuretic peptide level increased significantly at baseline in patients with HF than those without HF, while MSNA, blood pressure, and hemoglobin A1c did not differ between the 2 groups. Fasting blood glucose and homeostatic model assessment of insulin resistance did not change in either group after administering dapagliflozin. MSNA decreased significantly in both groups. However, the reduction in MSNA was significantly higher in patients with HF than patients with non-HF (-20.2±3.46 versus -9.38±3.65 bursts/100 heartbeats; =0.049), which was concordant with the decrease in brain natriuretic peptide. Conclusions Dapagliflozin significantly decreased MSNA in patients with type 2 diabetes regardless of its blood glucose-lowering effect. Moreover, the reduction in MSNA was more prominent in patients with HF than in patients with non-HF. These results indicate that the cardioprotective effects of sodium-glucose cotransporter 2 inhibitors may, in part, be attributed to improved SNA.
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http://dx.doi.org/10.1161/JAHA.121.022637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8751957PMC
November 2021

Association between Cardiovascular Health and Incident Atrial Fibrillation in the General Japanese Population Aged ≥40 Years.

Nutrients 2021 Sep 15;13(9). Epub 2021 Sep 15.

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa 920-8641, Japan.

This study explores the association between lifestyle behavior and incident atrial fibrillation (AF) in the general Japanese population. Japanese residents aged ≥40 years undergoing a national health checkup in Kanazawa City were included. We hypothesized that better lifestyle behavior is associated with lower incidence of AF. Lifestyle behavior was evaluated by the total cardiovascular health (CVH) score (0 = poor to 14 = ideal), calculated as the sum of the individual scores on seven modifiable risk factors: smoking status, physical activity, obesity, patterns of eating schedule, blood pressure, total cholesterol, and blood glucose. The association between CVH and incident AF was assessed, adjusting for other factors. A total of 37,523 participants (mean age 72.3 ± 9.6 years, 36.8% men, and mean total CVH score 9 ± 1) were analyzed. During the median follow-up period of 5 years, 703 cases of incident AF were observed. Using a low CVH score as a reference, the upper group (ideal CVH group) had a significantly lower risk of incident AF (hazard ratio [HR] = 0.79, 95% confidence interval 0.65-0.96, = 0.02), especially among those aged <75 years (HR = 0.68, 95% confidence interval 0.49-0.94, = 0.02). Thus, ideal CVH is independently associated with a lower risk for incident AF, particularly in younger Japanese individuals (<75 years).
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http://dx.doi.org/10.3390/nu13093201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467180PMC
September 2021

Human genetics and its impact on cardiovascular disease.

J Cardiol 2022 02 20;79(2):233-239. Epub 2021 Oct 20.

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

Cardiovascular disease (CVD) is a major cause of death worldwide. Given that CVD is a highly heritable trait, researchers have attempted to fully understand the genetic basis of CVD for a long time. The human genome comprises 3,100 Mbp per haploid genome and 6,200 Mbp in total (diploid genome). However, there is a tendency for rare genetic variations to exhibit a large effect size, whereas common genetic variations have a small effect on diseases, because of natural selection. In this sense, dividing genetic variations into two groups based on allele frequency (and effect sizes on diseases) is a good idea. We know there are several important genes (especially lipid-related genes) in which rare genetic variations are apparently associated with CVD risk, while a polygenic risk score comprising common genetic variations appears to work quite well among general populations. That information can be used not only for risk stratification but also for discoveries for novel pharmacologic targets. In this review article, we provide the important and simple idea that human genetics is important for CVD because it is a highly heritable trait, and we believe that it will lead to precision medicine in this field.
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http://dx.doi.org/10.1016/j.jjcc.2021.09.005DOI Listing
February 2022

Impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after catheter ablation of atrial fibrillation: insights from AF frontier ablation registry.

Heart Vessels 2022 Feb 15;37(2):327-336. Epub 2021 Sep 15.

National Hospital Organization Tokyo Medical Center, Tokyo, Japan.

The impact of catheter ablation for atrial fibrillation (AF) on cardiovascular events and mortality is controversial. We investigated the impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after AF ablation from a Japanese multicenter cohort of AF ablation. We investigated 3326 consecutive patients (25.8% female, mean age 63.3 ± 10.3 years) who underwent catheter ablation for AF from the atrial fibrillation registry to follow the long-term outcomes and use of anti coagulants after ablation (AF frontier ablation registry). The primary endpoint was a composite of stroke, transient ischemic attack, cardiovascular events, and all-cause death. During a mean follow-up of 24.0 months, 2339 (70.3%) patients were free from AF after catheter ablation, and the primary composite endpoint occurred in 144 (4.3%) patients. The AF nonrecurrence group had a significantly lower incidence of the primary endpoint (1.8 per 100 person-years) compared with the AF recurrence group (3.0 per 100 person-years, p = 0.003). The multivariate analysis revealed that freedom from AF (hazard ratio 0.61, 95% confidence interval 0.44-0.86, p = 0.005) was independently associated with the incidence of the composite event. In the multicenter cohort of AF ablation, sinus rhythm maintenance after catheter ablation was independently associated with lower rates of major adverse cardiac and cerebrovascular events.
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http://dx.doi.org/10.1007/s00380-021-01929-5DOI Listing
February 2022

Early Detection of Symptom Exacerbation in Patients With SARS-CoV-2 Infection Using the Fitbit Charge 3 (DEXTERITY): Pilot Evaluation.

JMIR Form Res 2021 Sep 16;5(9):e30819. Epub 2021 Sep 16.

Department of Health Promotion and Medicine of the Future, Kanazawa University, Kanazawa, Japan.

Background: Some patients with COVID-19 experienced sudden death due to rapid symptom deterioration. Thus, it is important to predict COVID-19 symptom exacerbation at an early stage prior to increasing severity in patients. Patients with COVID-19 could experience a unique "silent hypoxia" at an early stage of the infection when they are apparently asymptomatic, but with rather low SpO (oxygen saturation) levels. In order to continuously monitor SpO in daily life, a high-performance wearable device, such as the Apple Watch or Fitbit, has become commercially available to monitor several biometric data including steps, resting heart rate (RHR), physical activity, sleep quality, and estimated oxygen variation (EOV).

Objective: This study aimed to test whether EOV measured by the wearable device Fitbit can predict COVID-19 symptom exacerbation.

Methods: We recruited patients with COVID-19 from August to November 2020. Patients were asked to wear the Fitbit for 30 days, and biometric data including EOV and RHR were extracted. EOV is a relative physiological measure that reflects users' SpO levels during sleep. We defined a high EOV signal as a patient's oxygen level exhibiting a significant dip and recovery within the index period, and a high RHR signal as daily RHR exceeding 5 beats per day compared with the minimum RHR of each patient in the study period. We defined successful prediction as the appearance of those signals within 2 days before the onset of the primary outcome. The primary outcome was the composite of deaths of all causes, use of extracorporeal membrane oxygenation, use of mechanical ventilation, oxygenation, and exacerbation of COVID-19 symptoms, irrespective of readmission. We also assessed each outcome individually as secondary outcomes. We made weekly phone calls to discharged patients to check on their symptoms.

Results: We enrolled 23 patients with COVID-19 diagnosed by a positive SARS-CoV-2 polymerase chain reaction test. The patients had a mean age of 50.9 (SD 20) years, and 70% (n=16) were female. Each patient wore the Fitbit for 30 days. COVID-19 symptom exacerbation occurred in 6 (26%) patients. We were successful in predicting exacerbation using EOV signals in 4 out of 5 cases (sensitivity=80%, specificity=90%), whereas the sensitivity and specificity of high RHR signals were 50% and 80%, respectively, both lower than those of high EOV signals. Coincidental obstructive sleep apnea syndrome confirmed by polysomnography was detected in 1 patient via consistently high EOV signals.

Conclusions: This pilot study successfully detected early COVID-19 symptom exacerbation by measuring EOV, which may help to identify the early signs of COVID-19 exacerbation.

Trial Registration: University Hospital Medical Information Network Clinical Trials Registry UMIN000041421; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047290.
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http://dx.doi.org/10.2196/30819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448084PMC
September 2021

Decline in serum albumin concentration is a predictor of serious events in nonalcoholic fatty liver disease.

Medicine (Baltimore) 2021 Aug;100(31):e26835

Department of Gastroenterology, Kanazawa University Graduate School of Medical Sciences.

Abstract: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome, which includes diabetes mellitus and hyperlipidemia. A fraction of NAFLD patients develop nonalcoholic steatohepatitis, leading to cirrhosis associated with various serious complications, including hepatocellular carcinoma, gastroesophageal varices, cardiovascular events, and other organ malignancy. Although the incidence of chronic viral hepatitis with associated complications has gradually decreased as highly effective antiviral therapies have been established, the number of patients with steatohepatitis has been increasing.This retrospective study examined data of 229 patients from 22 hospitals in our region. We examined 155 cases of chronological data and assessed the development of liver fibrosis and evaluated hepatic reserve-related markers such as platelet count, FIB-4 index, prothrombin time, and serum albumin concentration. We analyzed the relationship of these chronological changes and the incidence of NAFLD related serious complications.Data related to liver fibrosis progression, albumin, and prothrombin time were significantly associated with the occurrence of serious complications associated with cirrhosis. We compared 22 event and 133 nonevent cases of chronological changes in the data per year and found that serum albumin concentration was significantly lower in the group that developed serious complications (event cases: -0.21 g/dL/year, nonevent cases: -0.04 g/dL/year (P < .001)). This albumin decline was only the associated factor with the event incidence by multivariate analysis (P < .01).Annual decline in serum albumin concentration in patients with NAFLD is associated with serious events from the outcome of multicenter retrospective study. This highlights its potential utility as a surrogate marker to assess the efficacy of prediction of NAFLD related serious events.
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http://dx.doi.org/10.1097/MD.0000000000026835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341320PMC
August 2021

Cardiac thrombus growth without D-dimer elevation in atrial fibrillation-mediated cardiomyopathy.

J Interv Card Electrophysiol 2021 Aug 11. Epub 2021 Aug 11.

Department of Cardiology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.

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http://dx.doi.org/10.1007/s10840-021-01042-7DOI Listing
August 2021

Association of Lower Urinary Tract Symptoms Based on the International Prostate Symptom Score and Cardiovascular Disease.

Circ J 2021 10 3;85(11):2092-2099. Epub 2021 Jul 3.

Department of Preventive Medicine, Northwestern University Feinberg School of Medicine.

Background: Because it is unclear whether lower urinary tract symptoms (LUTS) are associated with cardiovascular disease (CVD) in the Japanese population, we explored the association in general Japanese men aged 55-75 years.Methods and Results:The cross-sectional study included male participants who had both national health checkup data and the International Prostate Symptom Score (IPSS) in the same calendar year between 2009 and 2017. LUTS severity was evaluated by IPSS. A robust Poisson regression model was used to assess the association between LUTS severity and the composite CVD outcome [coronary artery disease (CAD), stroke, or atrial fibrillation (AF)] and each component of the composite outcome. Prevalence ratio (PR) was adjusted for conventional cardiovascular risk factors. Of 16,781 male participants (mean age, 67±5 years), mild LUTS were observed in 9,243 (55.1%); moderate, 6,445 (38.4%); and severe, 1,093 (6.5%). Compared with the mild LUTS group, moderate LUTS [PR 1.18, 95% confidence interval (CI) 1.10-1.25, P<0.001] and severe LUTS (PR 1.38, 95% CI 1.24-1.53, P<0.001) were significantly associated with a higher prevalence of CVD. LUTS severity was associated with higher prevalence of CAD and stroke, but not AF.

Conclusions: The severity of LUTS was associated with a higher prevalence of CVD, especially CAD and stroke, independent of conventional CVD risk factors.
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http://dx.doi.org/10.1253/circj.CJ-21-0278DOI Listing
October 2021

Does pulmonary vein isolation prolong QT interval?

Europace 2021 12;23(12):2046

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Science, 13-1 Takara-machi, Kanazawa 920-8641, Japan.

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http://dx.doi.org/10.1093/europace/euab152DOI Listing
December 2021
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