Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Advance online publication
Showing 1-50 articles out of 51 articles from Advance online publication
  • Kasumi Ishibuchi, Kenichi Fujii, Satoru Otsuji, Shin Takiuchi, Katsuyu ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Intervention
    Article ID: CJ-19-0421
    Published: August 14, 2019
    [Advance publication] Released: August 14, 2019
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    Background:Intracoronary (IC) administration of nicorandil has been proposed as an alternative choice of hyperemic agent for fractional flow reserve (FFR) measurements. This study evaluated the utility and validity of IC nicorandil administration alone to induce maximal hyperemia.

    Methods and Results:Two-hundred-seven patients with coronary artery disease listed for coronary angiography with FFR were prospectively enrolled. FFR was measured after (1) IC administration of nicorandil 2 mg (ICNIC2 mg); (2) continuous intravenous (IV) adenosine triphosphatase (ATP) infusion at 150 μg/kg/min (IVATP150); (3) IV ATP infusion at 210 μg/kg/min (IVATP210); (4) IC administration of 0.5 mg nicorandil during IVATP150 (ICNIC0.5 mg+IVATP150); (5) IC administration of 1 mg nicorandil during IVATP150 (ICNIC1 mg+IVATP150); and (6) IC administration of 2 mg nicorandil during IVATP150 (ICNIC2 mg+IVATP150). The average FFR values and the rate of achieving maximum hyperemia after ICNIC2 mg, IVATP150, IVATP210, ICNIC0.5 mg+IVATP150, ICNIC1 mg+IVATP150, and ICNIC2 mg+IVATP150 were 0.85±0.08, 0.89±0.08, 0.85±0.09, 0.84±0.08, 0.83±0.08, 0.83±0.08 (P<0.01), and 92%, 54%, 91%, 96%, 99%, 99% (P<0.01), respectively. The incidence of systolic aortic pressure drop, chest discomfort, and transient atrioventricular block increased in a dose-dependent manner after IV ATP infusion, but almost no adverse effects were observed after ICNIC2 mg.

    Conclusions:ICNIC2 mg produced a more pronounced hyperemia than continuous IV ATP, and might be the preferred method for assessment of FFR.

  • Yuan Zhong, Kai Tang, Hailing Li, Dongdong Zhao, Wenxin Kou, Shaojie X ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-19-0415
    Published: August 10, 2019
    [Advance publication] Released: August 10, 2019
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    Background:Atrial fibrillation (AF) is the most common arrhythmia with serious complications and a high rate of recurrence after catheter ablation. Recently, mutation ofMYL4was reported as responsible for familial atrial cardiomyopathy and AF. This study aimed to determine the association between polymorphism inMYL4with the onset and recurrence of AF.

    Methods and Results:A total of 7 single-nucleotide polymorphisms were selected by linkage disequilibrium and genotyped in 510 consecutive AF patients and 192 controls without structural heart disease. A total of 246 AF patients who underwent cryoballoon ablation had a 1-year scheduled follow-up study for AF recurrence. C allele and CC genotype of rs4968309 and A allele of rs1515751were associated with AF onset both before and after adjustment of covariation (age, sex, hypertension, and diabetes). AF type and left atrial size were different among the genotypes of rs4968309. Moreover, CC genotype of rs4968309 increased susceptibly of AF recurrence after cryoballoon ablation. The prevalence of hypertension was associated with rs1515752, and left atrial size was associated with the genotype of rs2071438.

    Conclusions:C allele and CC genotype of rs4968309 inMYL4were associated with AF onset and recurrence. Moreover, the A allele of rs1515751 had a significant association with AF onset. The polymorphisms ofMYL4can predict AF onset and prognosis after ablation in AF patients without structural heart disease.

  • Akio Chikata, Takeshi Kato, Kazuo Usuda, Masayuki Takamura
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-19-0466
    Published: August 10, 2019
    [Advance publication] Released: August 10, 2019
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  • Yuko Inoue, Chisato Izumi
    Type: EDITORIAL
    Article ID: CJ-19-0662
    Published: August 09, 2019
    [Advance publication] Released: August 09, 2019
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  • Shigetake Sasayama
    Type: IN MEMORIAM
    Article ID: CJ-66-0170
    Published: August 09, 2019
    [Advance publication] Released: August 09, 2019
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  • Yumi Munetsugu, Mitsuharu Kawamura, Toshihiko Gokan, Ko Ogawa, Yuya Na ...
    Type: ORIGINAL ARTICLE
    Subject Area: Arrhythmia/Electrophysiology
    Article ID: CJ-19-0021
    Published: August 08, 2019
    [Advance publication] Released: August 08, 2019
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    Background:Lethal ventricular arrhythmia (VA) can be initiated by idiopathic premature ventricular contractions (PVCs) originating from the left ventricular (LV) inferior wall. Furthermore, J-wave elevation in the inferior leads on ECG is sometimes associated with lethal VA. However, the relationship between these PVCs and J-wave elevation in patients with lethal VA is unclear, so we investigated it in the present study.

    Methods and Results:We studied 32 consecutive patients who underwent radiofrequency (RF) ablation of idiopathic PVCs with right bundle branch block (RBBB) and superior axis. Thee PVCs were originating from the inferior wall of the LV. Lethal VA was defined as ventricular fibrillation (VF) or ventricular tachycardia (VT) with loss of consciousness (LOC). Among 32 patients, 3 had VF and 2 had VT with LOC. Other 27 had non-lethal VA. Baseline clinical characteristics were not significantly difference between lethal and non-lethal VA. The ratio of J-wave elevation in lethal VA was significantly higher as compared with non-lethal VA (100% vs. 11.1%, P<0.0001). Furthermore, no patients with J-wave elevation in the inferior leads had recurrence of lethal VA after RF ablation of the PVCs.

    Conclusions:We speculate that J-wave elevation in the inferior leads might be a predictor of lethal VA initiated by PVCs with RBBB and superior axis. RF ablation of these PVCs was a useful method of treating lethal VA.

  • Hiroyuki Tsutsui, Shin-ichi Momomura, Akira Yamashina, Hiroaki Shimoka ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-19-0227
    Published: August 08, 2019
    [Advance publication] Released: August 08, 2019
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    Background:Increased heart rate (HR) is an independent risk factor for cardiovascular outcomes in chronic heart failure (HF). Ivabradine, anIfinhibitor, improved outcomes in patients with HF and reduced ejection fraction (HFrEF) in the SHIFT study. We evaluated its efficacy and safety in Japanese HFrEF patients in a randomized, double-blind, placebo-controlled phase III study: the J-SHIFT study. The main objective was to confirm a hazard ratio of <1 in the primary composite endpoint of cardiovascular death or hospital admission for worsening HF.

    Methods and Results:Patients with NYHA functional class II–IV, left ventricular EF ≤35%, and resting HR ≥75 beats/min in sinus rhythm under optimal medical therapy received ivabradine (n=127) or placebo (n=127). Mean reduction in resting HR was significantly greater in the ivabradine group (15.2 vs. 6.1 beats/min, P<0.0001). However, symptomatic bradycardia did not occur. A total of 26 (20.5%) patients in the ivabradine group and 37 (29.1%) patients in the placebo group had the primary endpoint event (hazard ratio 0.67, 95% CI 0.40–1.11, P=0.1179) during median follow-up of 589 days. Mild phosphenes were reported in 8 (6.3%) patients in the ivabradine group and 4 (3.1%) patients in the placebo group (P=0.3760).

    Conclusions:The J-SHIFT study supported the efficacy and safety of ivabradine for Japanese HFrEF patients, in accord with the SHIFT study.

  • Issei Komuro, Hidehiro Kaneko, Hiroyuki Morita, Mitsuaki Isobe, Hirofu ...
    Type: REVIEW
    Article ID: CJ-19-0562
    Published: August 06, 2019
    [Advance publication] Released: August 06, 2019
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    Heart failure pandemic is rapidly approaching in Japan, requiring nationwide actions. In particular, the Japanese Circulation Society and related societies launched the Stroke and Cardiovascular Disease Control Act, which was passed by the National Diet, as the first ever legislative policy measure against stroke and cardiovascular disease. In association with this, actions against heart failure pandemic from the scientific field are also important. Because heart failure pandemic is a critical problem not only in Japan but also in many developed countries, we believe the nationwide approach, as summarized here, will greatly contribute to the development of cardiovascular medicine, particularly the management and treatment of heart failure worldwide.

  • Kyoung Im Cho, Jongwook Yu, Toshio Hayashi, Seung Hwan Han, Kwang Kon ...
    Type: REVIEW
    Article ID: CJ-19-0624
    Published: August 06, 2019
    [Advance publication] Released: August 06, 2019
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    At present, atherosclerosis is one of the most important field in clinical and research medicine. Because it is closely related to cardiovascular (CV) and endocrine disorders such as coronary artery disease, cardiometabolic disorders, much research on how to manage atherosclerosis has been performed. The low-density lipoprotein cholesterol (LDL-C) concentration has been established as an independent risk factor for developing atherosclerosis, and considerable effort has been committed to educating both physicians and the general public on the importance of lowering LDL-C with statins. Although statins have already significantly improved CV outcomes, patients with LDL-C target levels achieved by intense statin therapy still have significant remaining CV risk. Statins already play a central role in managing hyperlipidemia; however, residual risk with statins is an important field of managing remaining CV risk. Recent studies have suggested residual cholesterol and inflammation risks in causing CV events. In the current review, we will discuss residual risk and suggest strategies to overcome it in the statins era.

  • Toshifumi Kudo
    Type: EDITORIAL
    Article ID: CJ-19-0658
    Published: August 06, 2019
    [Advance publication] Released: August 06, 2019
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  • Ho-Chang Kuo, Cheng-Tsung Pan, Ying-Hsien Huang, Fu-Chen Huang, Yeong- ...
    Type: ORIGINAL ARTICLE
    Subject Area: Valvular Heart Disease
    Article ID: CJ-19-0206
    Published: August 03, 2019
    [Advance publication] Released: August 03, 2019
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    Background:Kawasaki disease (KD) severely threatens young children’s health worldwide. The pathogenic mechanism of KD has not yet been solved, so there is still debate over whether KD is an infectious disease or an autoimmune disease.

    Methods and Results:To solve this problem, an immune repertoire analysis of KD was conducted. We collected blood cell RNA samples and prepared them into amplicons with iRepertoire kits. The amplicons were sequenced and analyzed with the iRepertoire pipeline. We first identified KD-specific VJ and VDJ forms that had the potential to serve as biomarkers of KD. In addition, the KD-specific VDJ forms were contributed mostly by immunoglobulin G. The D50 value analysis showed that B-cell diversity in KD is decreased, suggesting unique immunoglobulins are produced in KD. Moreover, V, D and J segment usage in IgA, IgG and IgM was consistent with previous KD studies. Further comparison showed no difference in CDR3 peptide length between KD and fever controls (subjects with fever but not diagnosed as KD), indicting KD had B-cell selection phenomenon that has a non-autoimmune pattern. The comparison of amino acid usage of the CDR3 region demonstrated a preference for hydrophilic amino acids in KD.

    Conclusions:The results of D50 value, VDJ usage and CDR3 peptide length analyses suggested the characteristics of infectious disease for KD.

  • Hiroshi Akazawa, Haruhiro Toko, Mutsuo Harada, Kazutaka Ueda, Satoshi ...
    Type: 2019 JCS REPORT
    Article ID: CJ-19-0587
    Published: August 03, 2019
    [Advance publication] Released: August 03, 2019
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    The 83rdAnnual Scientific Meeting of the Japanese Circulation Society was held in Yokohama, Japan, on March 29–31, 2019, just as the cherry blossoms came into full bloom. Because the environment around cardiovascular healthcare is rapidly changing, it becomes highly important to make a breakthrough at the dawn of a new era. The main theme of this meeting was “Renaissance of Cardiology for the Creation of Future Medicine”. The meeting benefited from the participation of 18,825 people, and there were in-depth and extensive discussions at every session, focusing on topics covering clinical and basic research, medical care provision system, human resource development, and public awareness in cardiovascular medicine. The meeting was completed with great success, and we greatly appreciate the tremendous cooperation and support from all affiliates.

  • Lei Xu, Yi-ru Wang, Pei-cheng Li, Bo Feng
    Type: ORIGINAL ARTICLE
    Subject Area: Vascular Biology and Vascular Medicine
    Article ID: CJ-19-0153
    Published: August 02, 2019
    [Advance publication] Released: August 02, 2019
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    Background:There is accumulating evidence that the AGEs-RAGE interaction plays an important role in accelerated atherosclerosis in diabetes. Our previous study showed that the AGEs-RAGE axis can reduce the cholesterol efflux of THP-1 macrophages through suppression of the expression of ABCG1 and that statins can inhibit the expression of RAGE. However, the role of statins in recovering the cholesterol efflux of macrophages reduced by AGEs has not been assessed.

    Methods and Results:ApoE−/−mice and THP-1 macrophages were both treated by AGEs or AGEs combined with anti-RAGE antibody (only in THP-1 cells), ALT711 and atorvastatin separately. Cholesterol efflux of THP-1 macrophages and murine peritoneal macrophages was tested by fluorescence microplate technique. RT-PCR and western blot analysis were used to measure the expression of RAGE and molecules included in cholesterol efflux. After co-incubating with atorvastatin and AGEs, reduction in lipid accumulation in THP-1 macrophages and improvement of lesions complexity occurred compared with treating by AGEs only. Atorvastatin increased cholesterol efflux and ABCG1 expression of macrophages, which were reduced by AGEs, and decreased the expression of RAGE at the same time.

    Conclusions:This study demonstrated that atorvastatin can recover the deleterious ABCG1-mediated cholesterol efflux induced by AGEs in THP-1 macrophages and murine peritoneal macrophages by downregulating RAGE expression. It may contribute to the protective action of atorvastatin in diabetic subjects with atherosclerosis.

  • Shozo Sueda
    Type: ORIGINAL ARTICLE
    Subject Area: Pediatric Cardiology and Adult Congenital Heart Disease
    Article ID: CJ-19-0433
    Published: August 02, 2019
    [Advance publication] Released: August 02, 2019
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    Background:Japanese Circulation Society (JCS) guidelines do not include adolescents with coronary artery spasm.

    Methods and Results:We recruited 18 adolescents less than 20 years old with vasospastic angina (VSA): 11 were Japanese and 3 had chest symptoms for >12 months before admission. ST-segment elevation was observed in 11 patients and none of the 18 patients had a fixed stenosis. Spasm provocation tests were performed in 9 patients and two-thirds had multiple spasms; 6 suffered from acute myocardial infarction and ventricular fibrillation occurred in 2 patients; 1 patient died and the remaining 17 patents survived.

    Conclusions:Clinical status of adolescents with VSA was as severe as in adults with refractory VSA. Cardiologists should cooperate with pediatricians to diagnose and treat adolescents with VSA. There is a need to establish the additional issues for adolescents with coronary spasm in the JCS guidelines.

  • Tadanobu Yoshikawa, Kenji Obayashi, Kimie Miyata, Tomo Nishi, Tetsuo U ...
    Type: ORIGINAL ARTICLE
    Subject Area: Epidemiology
    Article ID: CJ-19-0118
    Published: July 31, 2019
    [Advance publication] Released: July 31, 2019
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    Background:Decreased light reception because of cataracts leads to potential circadian misalignment, resulting in exacerbation of atherosclerosis; however, little is known about the association between cataracts and atherosclerosis in populations.

    Methods and Results:In this cross-sectional study, cataracts were graded using slit lamp biomicroscopy with the Lens Opacities Classification System III and carotid atherosclerosis was assessed based on carotid intima-media thickness (IMT) measured using ultrasonography of the common carotid artery in 442 elderly participants (mean age, 70.0 years). Cataract was defined as nuclear cataract grade ≥3.0, cortical cataract grade ≥2.0, or posterior subcapsular cataract grade ≥2.0 in both eyes. The mean and maximal carotid IMT was 0.86±0.15 mm and 1.07±0.29 mm, respectively. In multivariable analysis adjusted for potential confounders, the mean and maximal carotid IMT were significantly greater in the cataract group than in the non-cataract group by 0.04 mm (95% confidence interval (CI), 0.01–0.06) and 0.07 mm (95% CI, 0.01–0.12), respectively. Logistic regression analysis adjusted for confounders revealed a significantly higher odds ratio for carotid atherosclerosis (maximal carotid IMT ≥1.1 mm) in the cataract group than in the non-cataract group (odds ratio, 1.78; 95% CI, 1.14–2.78).

    Conclusions:Cataracts may be independently associated with subclinical carotid atherosclerosis in the elderly population, indicating a need for further prospective studies.

  • Hideki Ishii, Toyoaki Murohara
    Type: EDITORIAL
    Article ID: CJ-19-0600
    Published: July 31, 2019
    [Advance publication] Released: July 31, 2019
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  • Sho-ichi Yamagishi
    Type: REVIEW
    Article ID: CJ-19-0618
    Published: July 30, 2019
    [Advance publication] Released: July 30, 2019
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    Despite the early loss of glycemic differences between the original intensive therapy group and conventional treatment in the DCCT/EDIC and UKPDS 80 trials, a continued reduction in microvascular risk and risk reductions for emergency myocardial infarction and all-cause death were observed 10–30 years after the end of these trials. These observations demonstrated that so-called “metabolic memory” could cause chronic abnormalities in diabetic vessels that are not easily reversed, even by subsequent improvement in blood glucose levels, thus suggesting a long-term beneficial influence of early metabolic control; that is, legacy effects on the risk of vascular complications and death in patients with both type 1 and type 2 diabetes. Formation and accumulation of advanced glycation endproducts (AGEs) are known to progress at an accelerated rate under diabetes. Furthermore, AGEs are hardly degraded and remain for a long time in diabetic vessels even after glycemic control is improved. Therefore, AGEs could explain why former cumulative diabetic exposure could contribute to current progression of vascular complications in diabetes. Here, the clinical utility of measurement of serum and tissue accumulation levels of AGEs for evaluating the prevalence and severity of numerous types of cardiovascular disease is reviewed and novel therapeutic strategies that could target the AGE-RAGE axis in CVD are discussed.

  • Atsuko Nakayama, Hiroyuki Morita, Takayuki Fujiwara, Issei Komuro
    Type: ORIGINAL ARTICLE
    Subject Area: Preventive Medicine
    Article ID: CJ-19-0357
    Published: July 27, 2019
    [Advance publication] Released: July 27, 2019
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    Background:The effect of the sex ratio of the team of the attending doctors on clinical outcomes remains unknown.

    Methods and Results:This retrospective cohort study included 9,544 patients admitted between 2012 and 2018 for cardiovascular diseases. They were treated by teams of 3 attending doctors comprising a trainee doctor, middle-grade cardiologist who played the main role in the clinical management, and upper-grade cardiologist who was responsible for the management. We explored whether the sex of the attending doctors influenced the risk of emergency readmission within 30 days after discharge. The primary hospitalization periods were similar for male and female middle-grade cardiologists. The risk of emergency readmission of patients hospitalized with cardiovascular diseases was significantly higher for patients treated by male middle-grade cardiologists than in those treated by female middle-grade cardiologists (odds ratio: 2.09, P<0.01). This beneficial effect of treatment by female cardiologists was observed in younger (<65 years) patients, male patients, patients with New York Heart Association stages II–IV, and those with emergency primary hospitalization, and in medical teams led by a male upper-grade cardiologist.

    Conclusions:The risk of emergency readmission after discharge in patients hospitalized with cardiovascular diseases was ameliorated when treatment was performed by female middle-grade cardiologists. The combination of male and female cardiologists in the attending doctors’ team could result in better prognoses for cardiovascular patients.

  • Takuro Shirasu, Takatoshi Furuya, Motoki Nagai, Yukihiro Nomura
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiovascular Surgery
    Article ID: CJ-19-0386
    Published: July 27, 2019
    [Advance publication] Released: July 27, 2019
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    Background:Since endovascular aneurysm repair has become predominant, the issue of training young vascular surgeons in open abdominal aortic aneurysm (AAA) surgery has received significant attention. Through learning curve analysis, we aimed to determine the number of cases needed for young surgeons to achieve satisfactory open surgical skills.

    Methods and Results:A total of 562 consecutive patients who underwent open repair either by an attending surgeon (group A) or 6 young vascular surgeons (group Y) were included and assessed with regards to the preparation, clamp, and total operation times. Although some of the patients’ characteristics were different, the surgical procedures were comparable between the 2 groups. There was a clear trend towards a decrease in each 10 successive cases in group Y. The operation times in group A were constant at 72±30 (preparation), 48±10 (clamp), and 231±59 min (total), which were achieved by young vascular surgeons in 10, 30, and 10 cases, respectively. In the cumulative sum analysis, 25–27 cases were necessary for young vascular surgeons to enhance their surgical skills. The complication rate in group Y was no higher than that in group A.

    Conclusions:Young vascular surgeons can safely learn open AAA repair without increasing operation time or complications. Approximately 30 cases would be necessary to gain satisfactory surgical skills.

  • Toyoaki Murohara
    Type: MESSAGE FROM THE EDITOR-IN-CHIEF
    Article ID: CJ-66-0169
    Published: July 26, 2019
    [Advance publication] Released: July 26, 2019
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  • Naoki Fujimoto, Toru Sato, Keishi Moriwaki, Emiyo Sugiura, Shiro Nakam ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-19-0451
    Published: July 23, 2019
    [Advance publication] Released: July 23, 2019
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  • Hayato Tada, Hirofumi Okada, Akihiro Nomura, Satoshi Yashiro, Atsushi ...
    Type: ORIGINAL ARTICLE
    Subject Area: Molecular Cardiology
    Article ID: CJ-19-0317
    Published: July 20, 2019
    [Advance publication] Released: July 20, 2019
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    Background:A substantial proportion of patients clinically diagnosed as having familial hypercholesterolemia (FH) do not manifest causative mutation(s) in the FH genes such asLDLR,APOB, andPCSK9. We aimed to evaluate the effect of rare and deleterious mutation(s) inABCG5/ABCG8on hyper-low-density lipoprotein (LDL) cholesterolemia in individuals who meet the clinical criteria for FH.

    Methods and Results:We compared the LDL cholesterol (LDL-C) values among 487 subjects with FH; the subjects were grouped according to the presence of mutation(s) in FH andABCG5/ABCG8genes. We identified 276 individuals with a deleterious mutation in 1 FH gene (57%, monogenic FH), but found no causative mutations in 156 individuals (32%, mutation-negative). A total of 37 individuals had deleterious mutations inABCG5orABCG8, but not in FH genes (8%,ABCG5/ABCG8mutation carriers). Among these, 3 individuals had sitosterolemia (0.6%) with double mutations. We also identified 18 individuals with deleterious mutations in an FH gene andABCG5orABCG8(4%,ABCG5/ABCG8-oligogenic FH). Subjects without mutations had significantly higher polygenic scores than those in any other groups. LDL-C levels in oligogenic FH subjects were significantly higher than in the monogenic FH subjects. Moreover, sitosterol/lathosterol levels were significantly affected by those mutations.

    Conclusions:The results suggested that rare and deleterious mutations inABCG5/ABCG8contribute substantially to mimicking and exacerbation of the FH phenotype.

  • Jelena Kornej, Philipp Sommer
    Type: LETTER TO THE EDITOR
    Article ID: CJ-19-0558
    Published: July 20, 2019
    [Advance publication] Released: July 20, 2019
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  • Qiqi Wang, Chengui Zhuo, Liangrong Zheng
    Type: AUTHOR’S REPLY
    Article ID: CJ-19-0589
    Published: July 20, 2019
    [Advance publication] Released: July 20, 2019
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  • Kunihiro Matsushita, Yingying Sang, Jingsha Chen, Shoshana H. Ballew, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Epidemiology
    Article ID: CJ-19-0320
    Published: July 19, 2019
    [Advance publication] Released: July 19, 2019
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    Background:Cardiovascular guidelines include risk prediction models for decision making that lack the capacity to include novel predictors.

    Methods and Results:We explored a new “predictor patch” approach to calibrating the predicted risk from a base model according to 2 components from outside datasets: (1) the difference in observed vs. expected values of novel predictors and (2) the hazard ratios (HRs) for novel predictors, in a scenario of adding kidney measures for cardiovascular mortality. Using 4 US cohorts (n=54,425) we alternately chose 1 as the base dataset and constructed a base prediction model with traditional predictors for cross-validation. In the 3 other “outside” datasets, we developed a linear regression model with traditional predictors for estimating expected values of glomerular filtration rate and albuminuria and obtained their adjusted HRs of cardiovascular mortality, together constituting a “patch” for adding kidney measures to the base model. The base model predicted cardiovascular mortality well in each cohort (c-statistic 0.78–0.91). The addition of kidney measures using a patch significantly improved discrimination (cross-validated ∆c-statistic 0.006 [0.004–0.008]) to a similar degree as refitting these kidney measures in each base dataset.

    Conclusions:The addition of kidney measures using our new “predictor patch” approach based on estimates from outside datasets improved cardiovascular mortality prediction based on traditional predictors, providing an option to incorporate novel predictors to an existing prediction model.

  • Eriko Hasumi, Katsuhito Fujiu, Koki Nakanishi, Issei Komuro
    Type: RAPID COMMUNICATION
    Article ID: CJ-19-0399
    Published: July 19, 2019
    [Advance publication] Released: July 19, 2019
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    Background:His-bundle pacing is an emerging routine technique that avoids pacing-dependent side effects. However, the success rate of His-bundle pacing is not 100%.

    Methods and Results:Left bundle pacing or peri-left bundle pacing (LBP/peri-LBP) are recently developed techniques that directly capture the left bundle or ventricular tissue near the left bundle. We evaluated the success rate of LBP/peri-LBP in patients whose treatment with His-bundle pacing failed. In addition, we evaluated left ventricular contraction and desynchrony after LBP/peri-LBP.

    Conclusions:LBP/peri-LBP is an alternative ventricular pacing method in atrioventricular block in patients with failure of His-bundle pacing.

  • Yoshihito Arao, Akinori Sawamura, Masahiro Nakatochi, Takahiro Okumura ...
    Type: ORIGINAL ARTICLE
    Subject Area: Heart Failure
    Article ID: CJ-19-0333
    Published: July 18, 2019
    [Advance publication] Released: July 18, 2019
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    Background:Intravenous vasodilators are commonly used in patients with hypertensive acute decompensated heart failure (ADHF), but little is known about their optimal use in blood pressure (BP) management to avoid acute kidney injury (AKI). The purpose of this study was to investigate the association between systolic BP (SBP) changes and the incidence of AKI in patients with hypertensive ADHF.

    Methods and Results:Post-hoc analysis was performed on a prospectively enrolled cohort. We investigated 245 patients with ADHF and SBP >140 mmHg on arrival (mean age, 76 years; 40% female). We defined “SBP-fall” as the maximum percent reduction in SBP 6 h after intravenous treatment. AKI was defined as serum creatinine (SCr) ≥0.3 mg/dL, or urine output <0.5 mL/kg/h (n=66) at 48 h. Mean SBP and SCr levels on arrival were 180 mmHg and 1.21 mg/dL, respectively. Patients with AKI had significantly larger SBP-fall than the others (36.7±15.3% vs. 27.2±15.3%, P<0.0001). Logistic regression analysis showed an odds ratio per 10% SBP-fall for AKI of 1.49 (95% confidence interval 1.29–1.90, P=0.001). SBP-fall was significantly associated with the number of concomitant used intravenous vasodilators (P=0.001). The administration of carperitide was also independently associated with increased incidence of AKI.

    Conclusions:Larger SBP-fall from excessive vasodilator use is associated with increased incidence of AKI in patients with hypertensive ADHF.

  • Satoshi Yuda
    Type: EDITORIAL
    Article ID: CJ-19-0594
    Published: July 18, 2019
    [Advance publication] Released: July 18, 2019
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  • Mitsuru Ishii, Tomohiko Taniguchi, Takeshi Morimoto, Hisashi Ogawa, No ...
    Type: ORIGINAL ARTICLE
    Subject Area: Valvular Heart Disease
    Article ID: CJ-19-0247
    Published: July 17, 2019
    [Advance publication] Released: July 17, 2019
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    Background:There has not been a previous report on the long-term outcomes of those patients who refuse aortic valve replacement (AVR) despite physicians’ recommendations.

    Methods and Results:Among 3,815 consecutive patients with severe aortic stenosis (AS) enrolled in the CURRENT AS registry, the study population comprised 2,005 symptomatic patients, who were subdivided into 3 groups by their treatment strategy and the reasons for conservative strategy (Initial AVR group: n=905; Patient rejection group: n=256; Physician judgment group, n=844). The primary outcome measure was a composite of aortic valve-related death and heart failure hospitalization. Patients in the patient rejection group as compared with those in the physician judgment group were younger, and had less comorbidities, and lower surgical risk scores. The cumulative 5-year incidence of the primary outcome measure in the patient rejection group was markedly higher than that in the initial AVR group, and was similar to that in the physician judgment group (60.7%, 19.0%, and 66.4%, respectively).

    Conclusions:Patient rejection was the reason for non-referral to AVR in nearly one-quarter of the symptomatic patients with severe AS who were managed conservatively. The dismal outcome in patients who refused AVR was similar to that in patients who were not referred to AVR based on physician judgment despite less comorbidities and lower surgical risk scores in the former than in the latter.

  • Masayuki Sugimoto, Noriko Takahashi, Kiyoaki Niimi, Akio Kodama, Hiros ...
    Type: ORIGINAL ARTICLE
    Subject Area: Aortic Disease
    Article ID: CJ-19-0383
    Published: July 17, 2019
    [Advance publication] Released: July 17, 2019
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    Background:The effect of left renal vein division (LRVD) during open surgery (OS) for pararenal and juxtarenal abdominal aortic aneurysm (P/JRAA) on postoperative renal function remains controversial, so we focused on chronic renal decline (CRD) and separately examined renal volume as a surrogate index of split renal function.

    Methods and Results:The 115 patients with P/JRAA treated with OS from June 2007 to January 2017 were reviewed: 26 patients without LRVD were matched to 27 patients with LRVD according to preoperative chronic kidney disease (CKD) stage and proximal clamp sites. The effect of LRVD on CRD was investigated by a time-to-event analysis. During a median follow-up of 23.5 months, CRD occurred in 5 patients with LRVD and in 4 patients without LRVD. Comparison of freedom from CRD showed no significant difference between the matched groups (P=0.870). The separate renal volumes were evaluated before surgery and at 1 and 2 years of follow-up using CT images from 18 patients with LRVD. At 2 years, the mean renal volume had decreased by 15% in the left kidney and by 9% in the right kidney (P=0.052 and 0.148, respectively), but the left-to-right renal volume ratio showed no significant change (P=0.647).

    Conclusions:LRVD had no significant effect on CRD or left renal volume relative to the right renal volume for up to 2 years.

  • Satoshi Yamashita, Masao Saotome, Hiroshi Satoh, Jun Kajihara, Yusaku ...
    Type: ORIGINAL ARTICLE
    Subject Area: Metabolic Disorder
    Article ID: CJ-19-0110
    Published: July 12, 2019
    [Advance publication] Released: July 12, 2019
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    Background:Although previous studies have suggested a certain prevalence of Fabry disease (FD) in left ventricular hypertrophy (LVH) patients, the screening of FD is difficult because of its wide-ranging clinical phenotypes. We aimed to clarify the utility of combined measurement of plasma globotriaosylsphingosine (lyso-Gb3) concentration and α-galactosidase A activity (α-GAL) as a primary screening of FD in unexplained LVH patients.

    Methods and Results:Between 2014 and 2016, both lyso-Gb3 and α-GAL were measured in 277 consecutive patients (male 215, female 62, age 25–79 years) with left ventricular wall thickness >12 mm on echocardiogram: 5 patients (1.8%) screened positive (2 (0.7%) showed high lyso-Gb3 and 4 (1.4%) had low α-GAL levels). Finally, 2 patients (0.7%) were diagnosed with clinically significant FD. In 1 case, a female heterozygote with normal α-GAL levels had genetic variants of unknown significance and was diagnosed as FD by endomyocardial biopsy. The other case was a male chronic renal failure patient requiring hemodialysis, and he had a p.R112H mutation. In both cases there were high lyso-Gb3 levels.

    Conclusions:The serum lyso-Gb3 level can be relevant for clinically significant FD, and combined measurement of lyso-Gb3 and α-GAL can provide better screening of FD in unexplained LVH patients.

  • Minh Thu Tran Vu, Thuy Vy Nguyen, Nha Van Huynh, Hoang Tam Nguyen Thai ...
    Type: ORIGINAL ARTICLE
    Subject Area: Molecular Cardiology
    Article ID: CJ-19-0190
    Published: July 12, 2019
    [Advance publication] Released: July 12, 2019
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    Background:Hypertrophic cardiomyopathy (HCM) is associated primarily with pathogenic mutations in sarcomeric genes. The aim of this study was to identify the prevalence and distribution of disease-causing mutations in HCM-associated genes and the genotype-phenotype relationship in Vietnamese patients with HCM.

    Methods and Results:Genetic testing was performed by next-generation sequencing in 104 unrelated probands for 23 HCM-related genes and in 57 family members for the mutation(s) detected. Clinical manifestations were recorded for genotype-phenotype correlation analysis. Mutation detection rate was 43.4%. Mutations inMYBPC3accounted for 38.6%, followed byTPM1(20.5%),MYH7(18.2%),TNNT2(9.1%),TNNI3(4.5%) andMYL2(2.3%). A mutation inGLAassociated with Fabry disease was found in 1 patient. A mutation inTPM1(c.842T>C, p.Met281Thr) was identified in 8 unrelated probands (18.2%) and 8 family members from 5 probands. Genotype-positive status related toMYH7,TPM1, andTNNT2mutations was associated with severe clinical manifestations.MYH7-positive patients displayed worse prognosis compared withMYBPC3-positive patients. Interestingly,TPM1c.842T>C mutation was associated with high penetrance and severe HCM phenotype.

    Conclusions:We report for the first time the prevalence of HCM-related gene variants in Vietnamese patients with HCM.MYH7,TPM1, andTNNT2mutations were associated with unfavorable prognosis.

  • Yukihito Higashi, Tetsuro Miyata, Hiroshi Shigematsu, Hideki Origasa, ...
    Type: ORIGINAL ARTICLE
    Subject Area: Peripheral Vascular Disease
    Article ID: CJ-19-0088
    Published: July 10, 2019
    [Advance publication] Released: July 10, 2019
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    Background:Guidelines for peripheral arterial disease (PAD) recommend long-term antiplatelet therapy in symptomatic patients to reduce cardiovascular morbidity and mortality risk. Although diabetes is a known risk factor for PAD, PAD has been undertreated in these patients. This study aimed to evaluate risk factors for major amputation in patients with diabetes undergoing antiplatelet therapy for PAD.

    Methods and Results:This retrospective analysis of a 2-year observational cohort study (1,745 clinics in Japan, September 2009–2013) evaluated predictors of amputation in patients with diabetes undergoing antiplatelet therapy for PAD. Among 4,016 eligible patients, 52 had an amputation during follow-up. Amputation risk (Cox regression analysis) was predicted at baseline by history of lower extremity revascularization/amputation (hazard ratio [HR]: 2.92; 95% confidence interval [CI]: 1.39, 6.14), chronic kidney disease (HR: 4.19; 95% CI: 1.95, 8.97), and comorbid cerebrovascular and heart disease (HR: 3.32; 95% CI: 1.19, 9.30), and was unaffected by choice of oral antiplatelet therapy. In patients with PAD and diabetes, amputation event rate was highest for those with ankle-brachial pressure index (ABI) <0.40 and progressively decreased at higher ABI cut-offs.

    Conclusions:These findings inform real-world understanding of PAD in diabetic patients receiving antiplatelet therapy in Japan, and showed that ABI <0.4 was the strongest risk factor for amputation.

  • Eun Kyoung Kim, Joo-Yong Hahn, Taek Kyu Park, Joo Myung Lee, Young Bin ...
    Type: ORIGINAL ARTICLE
    Subject Area: Ischemic Heart Disease
    Article ID: CJ-19-0237
    Published: July 09, 2019
    [Advance publication] Released: July 09, 2019
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    Background:The association between a change in diastolic function (DF) and long-term clinical outcomes in patients undergoing percutaneous coronary intervention (PCI) is unknown. The aim of this study was to investigate the prognostic effect of changes in diastolic dysfunction in patients undergoing PCI.

    Methods and Results:Consecutive patients who underwent PCI and echocardiography before and after revascularization were prospectively included. Major adverse cardiac event (MACE) was defined as a composite of cardiac death, myocardial infarction, and repeat revascularization. A total of 1,235 patients were identified. Baseline diastolic dysfunction was present in 1,033 patients (83.6%). At follow-up echocardiography, DF had worsened in 219 (17.8%) patients and was unchanged in 623 patients (50.4%). The risk of MACE was significantly higher in the worsened DF group compared with the unchanged DF group (adjusted hazard ratio [aHR]: 2.15; 95% confidence interval [CI]: 1.59 to 2.90; P<0.001) and the improved or normal DF group (aHR: 2.20; 95% CI, 1.49 to 3.27; P<0.001). Patients with worsened DF consistently had a higher risk of MACE in various subgroups, especially irrespective of left ventricular systolic function.

    Conclusions:Aggravation of DF was independently associated with an increased risk of MACE in patients undergoing PCI. Evaluating changes in DF after PCI is a simple but useful method for predicting long-term clinical outcomes.

  • Shinya Tanaka, Kentaro Kamiya, Nobuaki Hamazaki, Ryota Matsuzawa, Kohe ...
    Type: ORIGINAL ARTICLE
    Subject Area: Cardiac Rehabilitation
    Article ID: CJ-19-0136
    Published: July 06, 2019
    [Advance publication] Released: July 06, 2019
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    Background:Evidence for the prognostic value of gait speed is largely based on a single measure at baseline, so we investigated the prognostic significance of change in gait speed in hospitalized older acute heart failure (AHF) patients.

    Methods and Results:This retrospective study was performed in a cohort of 388 AHF patients ≥60 years old (mean age: 74.8±7.8 years, 228 men). Routine geriatric assessment included gait speed measurement at baseline and at discharge. The primary outcome of this study was all-cause death. Gait speed increased from 0.74±0.25 m/s to 0.98±0.27 m/s after 13.5±11.0 days. Older age, shorter height and lower hemoglobin level at admission, prior HF admission, and higher baseline gait speed were independently associated with lesser improvement in gait speed. A total of 80 patients died and 137 patients were readmitted for HF over a mean follow-up period of 2.1±1.9 years. In multivariate analyses, change in gait speed showed inverse associations with all-cause death (hazard ratio [HR] per 0.1 m/s increase: 0.83; 95% confidence interval [CI]: 0.73 to 0.95; P=0.006) and with risk of readmission for HF (HR: 0.91; 95% CI: 0.83 to 0.99; P=0.036).

    Conclusions:Short-term improvement in gait speed during hospitalization was associated with reduced risks of death and readmission for HF in older patients with AHF.

  • Kihyun Kim, Jaewon Oh, Seung-Tae Lee, Hyo Sup Shim, Seok-Min Kang
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-19-0281
    Published: June 26, 2019
    [Advance publication] Released: June 26, 2019
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  • Kiyoshi Asakura, Yoshiyasu Minami, Takao Shimohama, Junya Ako
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-19-0302
    Published: May 28, 2019
    [Advance publication] Released: May 28, 2019
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  • Songwen Chen, Keping Yang, Xiaofeng Lu, Shaowen Liu
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-19-0315
    Published: May 28, 2019
    [Advance publication] Released: May 28, 2019
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  • Nao Konagai, Shigefumi Fukui, Masataka Kitano, Kazuto Fujimoto, Tatsuy ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-19-0144
    Published: May 24, 2019
    [Advance publication] Released: May 24, 2019
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  • Takeshi Yagyu, Kazufumi Ida, Teruo Noguchi, Satoshi Yasuda
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-19-0143
    Published: May 11, 2019
    [Advance publication] Released: May 11, 2019
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  • Tomoyuki Umemoto, Shun Nakagama, Tetsumin Lee, Taishi Yonetsu
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-19-0203
    Published: May 09, 2019
    [Advance publication] Released: May 09, 2019
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  • Tatsuyuki Sato, Junichi Ishida, Toshiya Kojima, Issei Komuro
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-19-0010
    Published: March 29, 2019
    [Advance publication] Released: March 29, 2019
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  • Kenji Onoue, Genzou Takemura, Tomoya Nakano, Nagisa Miyazaki, Akiko Ts ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-19-0127
    Published: March 29, 2019
    [Advance publication] Released: March 29, 2019
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  • Yuta Okabe, Hiro Yamasaki, Yukio Sekiguchi, Kazutaka Aonuma, Akihiko N ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-19-0050
    Published: March 27, 2019
    [Advance publication] Released: March 27, 2019
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  • Yasuhisa Nakao, Jun Aono, Tatsuro Tasaka, Teruyoshi Uetani, Haruhiko H ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-18-1039
    Published: March 21, 2019
    [Advance publication] Released: March 21, 2019
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  • Munemitsu Otagaki, Koichiro Matsumura, Kenichi Fujii, Hiromi Kin, Yosh ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-18-1248
    Published: March 09, 2019
    [Advance publication] Released: March 09, 2019
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  • Makoto Hoyano, Kazuyuki Ozaki, Kota Nishida, Ryohei Sakai, Naoki Kubot ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-18-1229
    Published: March 07, 2019
    [Advance publication] Released: March 07, 2019
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  • Seigo Miyoshi, Takuya Matsumoto, Teruki Kidani, Eiji Sugimoto, Yukihir ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-18-1249
    Published: March 07, 2019
    [Advance publication] Released: March 07, 2019
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  • Hiroaki Tabata, Hirohiko Motoki, Takahiro Sakai, Ayako Okada, Koichiro ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-18-1102
    Published: March 06, 2019
    [Advance publication] Released: March 06, 2019
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  • Shoko Nakagawa, Takeshi Aiba, Kenzaburo Nakajima, Naoya Kataoka, Tsuka ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-18-1306
    Published: March 06, 2019
    [Advance publication] Released: March 06, 2019
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