Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Advance online publication
Showing 1-50 articles out of 105 articles from Advance online publication
  • Makoto Murata, Yasuyuki Kobayashi, Hitoshi Adachi
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0261
    Published: October 28, 2021
    [Advance publication] Released: October 28, 2021
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    Supplementary material

    Background:Minute ventilation/carbon dioxide production (V̇E/V̇CO2) is a variable of cardiopulmonary exercise testing (CPET), which is evaluated by arterial CO2pressure and ventilation-perfusion mismatch via invasive methods. This study evaluated substitute non-invasively obtained variables for minimum V̇E/V̇CO2(Min) and V̇E vs. V̇CO2slope (Slope) and the relationship between Min and Slope.

    Methods and Results:This study enrolled 1,052 patients with heart disease who underwent CPET and impedance cardiography simultaneously. At first, the correlations between the end-tidal CO2pressure (PETCO2), tidal volume/respiratory rate (TV/RR) ratio, V̇E and V̇CO2Y-intercept (Y-int), and cardiac index (CI) and the Min and Slope were investigated. Second, the correlation between Min and Slope was investigated. PETCO2showed the largest correlation value among the 4 variables. These 4 variables could reveal 84.2% and 81.9% of Min and Slope, respectively. Although Slope correlated with Min (R=0.868) and predicted 78.9% of Min, considering these 4 variables, Slope+Y-int was more strongly correlated with Min (R=0.940); the Slope+Y-int revealed 90.6% of the Min relationship in the multiple regression analysis.

    Conclusions:Over 80% of the Min and Slope values were revealed with the above-mentioned 4 variables collected non-invasively. The formula, Min∝Slope+Y-int, can reveal >90% of the Min/Slope relationships, and the Y-int may be a crucial factor to clarify the relationship between Min and Slope.

  • Tatsuo Ueda, Hiromitsu Hayashi, Takahiro Ando, Kotomi Iwata, Hidemasa ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0541
    Published: October 28, 2021
    [Advance publication] Released: October 28, 2021
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    Supplementary material

    Background:Although the high-attenuating crescent (HAC) sign can indicate aortic aneurysm (AA) impending rupture, the relation of its computed tomography (CT) value to the aneurysmal status remains unclear. This study compared the HAC sign CT-attenuation values among rupture, impending rupture, and non-rupture AA cases.

    Methods and Results:This included 76 patients (mean age: 77.0 years) diagnosed with HAC sign-associated AA between January 2005 and July 2015. The CT-attenuation values of the HAC sign (H) and aortic lumen (A) using region-of-interest methodology were measured and the H/A ratio was calculated. The study classified patients into the rupture group (R-G, n=36), impending rupture group (IR-G, n=16), and non-rupture group (NR-G, n=24); the H and the H/A ratio were compared among them. Additionally, the H and the H/A ratio cut-offs between the IR-G and NR-G groups were evaluated. The H and the H/A ratio were significantly higher in the R-G and IR-G than in the NR-G (both P<0.001); the H/A ratio was significantly higher in the R-G than in the IR-G (P=0.038). The optimal cut-off for H between the IR-G and NR-G was 50.3 Hounsfield units (area under the curve [AUC]=0.875; sensitivity=87.5%; specificity=87.5%), and that for the H/A ratio was 1.3 (AUC=0.909; sensitivity=91.7%; specificity=87.5%).

    Conclusions:Among patients with AA, the H and the H/A ratio were significantly higher in cases of rupture and impending rupture than in those of non-rupture.

  • Eiji Shibahashi, Kentaro Jujo
    Type: EDITORIAL
    Article ID: CJ-21-0798
    Published: October 28, 2021
    [Advance publication] Released: October 28, 2021
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  • Yu Nakagama, Masamichi Ito
    Type: EDITORIAL
    Article ID: CJ-21-0802
    Published: October 28, 2021
    [Advance publication] Released: October 28, 2021
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  • Naoya Kurata, Masaharu Masuda, Takashi Kanda, Mitsutoshi Asai, Osamu I ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0527
    Published: October 27, 2021
    [Advance publication] Released: October 27, 2021
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    Supplementary material

    Background:The efficacy of ablation targeting low-voltage areas (LVAs) is controversial, although LVA presence is well known to be associated with atrial fibrillation (AF) recurrence after ablation. AF substrate may not localize within LVAs.

    Methods and Results:This observational study enrolled 405 consecutive patients who underwent an initial AF ablation procedure. The left atrial (LA) voltage map was obtained after pulmonary vein isolation. LVAs were defined as areas with voltage <0.5 mV. To estimate whole LA electrophysiological degeneration, mean regional voltage at each of the 6 regions and LA total conduction velocity were measured. LVAs existed in 143 of 405 (35.3%) patients. Patients with LVAs demonstrated lower mean regional voltages throughout all 6 regions compared to those without LVAs (1.3 [1.8, 0.8] vs. 0.6 [1.0, 0.2] mV for the anterior wall, P<0.001). In contrast, LA conduction velocity was lower in patients with LVAs than in those without (0.89 [1.01, 0.74] vs. 0.93 [1.03, 0.87] m/s, P<0.001). Multivariate analysis revealed that low LA total conduction velocity and a higher number of regions with mean voltage reduction were independently associated with AF recurrence, although LVA presence was not.

    Conclusions:Patients with localized LA LVAs were characterized by whole LA electrophysiological degeneration as assessed by mean regional voltage and conduction velocity. In addition, whole LA electrophysiological degeneration parameters were well associated with AF recurrence.

  • Samira R. Aili, Phillip Lo, Jeanette E. Villanueva, Yashutosh Joshi, S ...
    Type: REVIEW
    Article ID: CJ-21-0819
    Published: October 27, 2021
    [Advance publication] Released: October 27, 2021
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    Supplementary material

    Background:Frailty is prevalent in patients with heart failure (HF) and associated with increased morbidity and mortality. Hence, there has been increased interest in the reversibility of frailty following treatment with medication or surgery. This systematic review aimed to assess the reversibility of frailty in patients with HF before and after surgical interventions aimed at treating the underlying cause of HF. It also aimed to assess the efficacy of cardiac rehabilitation and prehabilitation in reversing or preventing frailty in patients with HF.

    Methods and Results:Searches of PubMed, MEDLINE and Academic Search Ultimate identified studies with HF patients undergoing interventions to reverse frailty. Titles, abstracts and full texts were screened for eligibility based on the PRISMA guidelines and using predefined inclusion/exclusion criteria in relation to participants, intervention, control, outcome and study design. In total, 14 studies were included: 3 assessed the effect of surgery, 7 assessed the effect of rehabilitation programs, 2 assessed the effect of a prehabilitation program and 2 assessed the effect of program interruptions on HF patients.

    Conclusions:Overall, it was found that frailty is at least partially reversible and potentially preventable in patients with HF. Interruption of rehabilitation programs resulted in deterioration of the frailty status. Future research should focus on the role of prehabilitation in mitigating frailty prior to surgical intervention.

  • Yu Sato, Akiomi Yoshihisa, Ryohei Takeishi, Himika Ohara, Yukiko Sugaw ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0686
    Published: October 26, 2021
    [Advance publication] Released: October 26, 2021
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    Supplementary material

    Background:It has recently been reported that the simplified Academic Research Consortium for High Bleeding Risk (ARC-HBR) definition, which excludes 6 rare criteria, is comparable to the original ARC-HBR definition in predicting major bleeding in patients with coronary artery disease (CAD) who undergo percutaneous coronary intervention. In this study, we investigated whether the simplified ARC-HBR definition could be applied to patients with heart failure (HF) to identify those at high bleeding risk (HBR).

    Methods and Results:In all, 2,437 patients hospitalized for HF were enrolled in this study. Patients were divided into 2 groups based on the simplified ARC-HBR definition: those at HBR (n=2,026; 83.1%) and those not (non-HBR group; n=411; 16.9%). The HBR group was older (72.0 vs. 61.0 years; P<0.001) and had a lower prevalence of CAD (31.1% vs. 36.5%; P=0.034) than the non-HBR group. Kaplan-Meier analysis showed that post-discharge bleeding events defined as hemorrhagic stroke or gastrointestinal bleeding were more frequent in the HBR than non-HBR group (log-rank P<0.001). The simplified ARC-HBR definition accurately predicted bleeding events (Fine-Gray model; hazard ratio 2.777, 95% confidence interval 1.464–5.270, P=0.001).

    Conclusions:The simplified ARC-HBR definition predicts a high risk of bleeding events in patients with HF.

  • Yasushi Matsuzawa, Masami Kosuge, Kazuki Fukui, Hiroshi Suzuki, Kazuo ...
    Type: REVIEW
    Article ID: CJ-21-0807
    Published: October 22, 2021
    [Advance publication] Released: October 22, 2021
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    Acute cardiovascular disease, such as acute myocardial infarction and aortic disease, can lead to a serious life-threatening state within minutes to hours, so early accurate diagnosis, and appropriate treatment without delay are essential. To provide high-quality and timely treatment, 24-h availability of medical staff and cardiologists, as well as a cardiac catheterization laboratory are needed. In Japan, the number of patients with acute cardiovascular disease is increasing with the aging population and westernization of lifestyle; however, workstyle reforms for physicians, including a policy to limit overtime work, have been legislated. Under these conditions, it is necessary to centralize hospitals that treat cardiovascular emergency diseases as high-volume centers and build a patient triage system for allocating patients before hospital arrival. The prehospital 12-lead electrocardiogram (ECG) plays a central role in prehospital diagnosis and triage, and its importance will increase in future. We discuss the current and future state of the cardiovascular emergency medical care system utilizing prehospital 12-lead ECG in urban areas of Japan.

  • Mari Ishida, Chisa Matsumoto, Keisuke Kida, Memori Fukuda, Nobuyuki Ka ...
    Type: JCS STATEMENT
    Article ID: CJ-21-0822
    Published: October 22, 2021
    [Advance publication] Released: October 22, 2021
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    Supplementary material
  • Hiroshi Banno, Masayuki Sugimoto, Tomohiro Sato, Shuta Ikeda, Yohei Ka ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0574
    Published: October 21, 2021
    [Advance publication] Released: October 21, 2021
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    Supplementary material

    Background:Not every elderly person is frail, and whether it would be beneficial to perform endovascular aneurysm repair (EVAR) solely because a patient is older is unclear. This study aimed to compare the results of EVAR and open surgical repair (OSR) in elderly individuals.

    Methods and Results:From May 1998 to March 2021, 828 EVAR patients and 886 OSR patients with abdominal aortic aneurysm (AAA) were reviewed. Patients aged ≥80 years were included among them. After propensity score matching by age, sex, and American Society of Anesthesiologists (ASA) classification, the outcomes were compared between patients who underwent EVAR and OSR. The study cohort was composed of 351 EVAR patients and 90 OSR patients. The groups had similar comorbidities, except that EVAR patients were significantly older and had higher ASA classifications. After propensity score matching, 79 pairs of patients were selected. The 30-day mortality (0 vs. 1.2%) and aneurysm-related death (ARD) rates during follow up (2.3% vs. 2.3%, respectively) were similar between the groups. Kaplan-Meier curves revealed that estimated overall survival and freedom from ARD were also similar.

    Conclusions:This study suggests that EVAR cannot improve survival outcomes compared with OSR if applied solely because a patient is aged ≥80 years. Not only age but also other risk factors and quality of life after surgery need to be further studied.

  • Kensuke Takagi, Teruo Noguchi
    Type: EDITORIAL
    Article ID: CJ-21-0784
    Published: October 21, 2021
    [Advance publication] Released: October 21, 2021
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  • Satoru Takahashi, Sei Komatsu, Chikao Yutani, Mitsuhiko Takewa, Tomoki ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-21-0767
    Published: October 20, 2021
    [Advance publication] Released: October 20, 2021
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    Supplementary material
  • Naofumi F. Sumitomo, Kazuki Kodo, Jun Maeda, Masaru Miura, Hiroyuki Ya ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0559
    Published: October 15, 2021
    [Advance publication] Released: October 15, 2021
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    Background:The correlation between the Z-score of the left ventricular (LV) diameter and the LV volume-overload due to pulmonary over-circulation in children with ventricular septal defect (VSD) or patent ductus arteriosus (PDA) remains unclear.

    Methods and Results:The present, retrospective study enrolled 70 children (aged 0.3–16.8 years; 33 males, 37 females) with a diagnosis of isolated VSD and/or PDA who underwent cardiac catheterization (CC) between 2015 and 2019. Patients with chromosomal/genetic anomalies, growth disorder, right-ventricular enlargement or other conditions causing LV enlargement were excluded. Echocardiographic parameters were retrospectively evaluated from the medical records, converted to a Z-score, then compared with CC data. The pulmonary-systemic flow ratio on CC (cQp/Qs) correlated significantly with the Z-score of both the LV end-diastolic diameter (Zd) (r=0.698, P<0.0001) and LV end-systolic diameter (r=0.593, P<0.0001). Regression analysis and curve-fitting were used to predict the cQp/Qs based on the Zd, and a significant regression equation was found on cubic regression (R2of 0.524, P<0.0001) showing a strong correlation with the cQp/Qs (r=0.724, P<0.0001).

    Conclusions:The Z-score of the LV diameter can be a useful, non-invasive marker for evaluating LV volume overload and determining the surgical indications in children with VSD or PDA because of its strong correlation with the cQp/Qs.

  • Yoshihiro Yamada, Keiki Sugi, Kenji Fukushima, Toshihiro Muramatsu, Sh ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-21-0763
    Published: October 14, 2021
    [Advance publication] Released: October 14, 2021
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    Supplementary material
  • Kensaku Nishihira, Yoshisato Shibata
    Type: EDITORIAL
    Article ID: CJ-21-0797
    Published: October 14, 2021
    [Advance publication] Released: October 14, 2021
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  • Nobuhiro Hara, Tetsumin Lee, Toshihiro Nozato, Mao Terui Matsuyama, Sh ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0588
    Published: October 12, 2021
    [Advance publication] Released: October 12, 2021
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    Supplementary material

    Background:The efficacy of direct oral anticoagulants (DOACs) compared with warfarin for the treatment of venous thromboembolism (VTE), and the recurrence of VTE after discontinuation of anticoagulation therapy in research are limited.

    Methods and Results:This retrospective study enrolled 893 patients with acute VTE between 2011 and 2019. The cohort was divided into the transient risk, unprovoked, continued cancer treatment, and cancer remission groups. The following were compared between DOACs and warfarin: composite outcome of all-cause death, VTE recurrence, bleeding and composite outcome of VTE-related death, recurrence and bleeding. In the continued cancer treatment group, more bleeding was seen in warfarin-treated patients than in patients treated with DOACs (53.2% vs. 31.2%, [P=0.048]). In addition, composite outcome of VTE-related death and recurrence after discontinuation of anticoagulation therapy (n=369) was evaluated. The continued cancer treatment group (multivariate analysis: HR: 3.62, 95% CI: 1.84–7.12, P<0.005) and bleeding-related discontinuation of therapy (HR: 2.60, 95% CI: 1.32–5.13, P=0.006) were independent predictors of the event after discontinuation of anticoagulation therapy. VTE recurrence after discontinuation of anticoagulation therapy in the cancer remission group was 1.6% and a statistically similar occurrence was found in the transient risk group (12.4%) (P=0.754).

    Conclusions:DOACs may decrease bleeding incidence in patients continuing to receive cancer treatment. In patients with bleeding-related discontinuation of anticoagulation therapy, VTE recurrence may increase. Discontinuation of anticoagulant therapy might be a treatment option in patients who have completed their cancer treatment.

  • Kazunori Omote, Barry A. Borlaug
    Type: REVIEW
    Article ID: CJ-21-0795
    Published: October 12, 2021
    [Advance publication] Released: October 12, 2021
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    The left atrium (LA) plays an important role in facilitating left ventricular (LV) filling by acting as a reservoir, passive conduit, and active booster pump, as well as a regulator of blood volume through A-type natriuretic peptide secretion in response to stimulation by mechanical stretch of the cavity. LA myopathy has emerged as one of the most important non-LV contributors to disease progression in heart failure with preserved ejection fraction (HFpEF). LA dysfunction is common in HFpEF and is associated with more severe pulmonary vascular disease and right ventricular dysfunction, and increases the risk of incident atrial fibrillation or atrial functional mitral regurgitation, leading to limitations in cardiac output reserve and reduced exercise capacity. LA deformation assessed by 2-dimensional speckle-tracking echocardiography is useful for estimating abnormal hemodynamics or exercise capacity, discriminating HFpEF from non-cardiac dyspnea and is an independent predictor of adverse outcome in HFpEF. Thus, interventions directly targeting LA myopathy may improve outcomes in HFpEF with LA myopathy. This review provides information regarding the physiology of the LA in patients with HFpEF and discusses the importance of evaluation of LA function, management issues, and future directions through ongoing trials of medical interventions.

  • Kensuke Ihara, Tetsuo Sasano
    Type: EDITORIAL
    Article ID: CJ-21-0770
    Published: October 09, 2021
    [Advance publication] Released: October 09, 2021
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  • Xue Zhou, Keijiro Nakamura, Naohiko Sahara, Takahito Takagi, Yasutake ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0622
    Published: October 08, 2021
    [Advance publication] Released: October 08, 2021
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    Supplementary material

    Background:Radiofrequency catheter ablation (RFCA) is an effective therapy for atrial fibrillation (AF). However, it the problem of AF recurrence remains. This study investigates whether a deep convolutional neural network (CNN) can accurately predict AF recurrence in patients with AF who underwent RFCA, and compares CNN with conventional statistical analysis.

    Methods and Results:Three-hundred and ten patients with AF after RFCA treatment, including 94 patients with AF recurrence, were enrolled. Nine variables are identified as candidate predictors by univariate Cox proportional hazards regression (CPH). A CNNSurv model for AF recurrence prediction was proposed. The model’s discrimination ability is validated by a 10-fold cross validation method and measured by C-index. After back elimination, 4 predictors are used for model development, they are N-terminal pro-BNP (NT-proBNP), paroxysmal AF (PAF), left atrial appendage volume (LAAV) and left atrial volume (LAV). The average testing C-index is 0.76 (0.72–0.79). The corresponding calibration plot appears to fit well to a diagonal, and the P value of the Hosmer-Lemeshow test also indicates the proposed model has good calibration ability. The proposed model has superior performance compared with the DeepSurv and multivariate CPH. The result of risk stratification indicates that patients with non-PAF, higher NT-proBNP, larger LAAV and LAV would have higher risks of AF recurrence.

    Conclusions:The proposed CNNSurv model has better performance than conventional statistical analysis, which may provide valuable guidance for clinical practice.

  • Hiroyuki Miura, Chiaki Yokota
    Type: EDITORIAL
    Article ID: CJ-21-0769
    Published: October 08, 2021
    [Advance publication] Released: October 08, 2021
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  • Masao Yoshinaga, Hitoshi Horigome, Mamoru Ayusawa, Kazushi Yasuda, Shi ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0376
    Published: October 06, 2021
    [Advance publication] Released: October 06, 2021
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    Supplementary material

    Background:The usefulness of electrocardiographic (ECG) voltage criteria for diagnosing hypertrophic cardiomyopathy (HCM) in pediatric patients is poorly defined.

    Methods and Results:ECGs at the 1st grade (mean [±SD] age 6.6±0.3 years) were available for 11 patients diagnosed with HCM at around the 7th grade (13.2±0.3 years). ECGs were available for another 64 patients diagnosed with HCM in the 1st (n=15), 7th (n=32), and 10th (n=17) grades. Fifty-one voltage criteria were developed by grade and sex using 62,841 ECGs from the general population. Voltage criteria were set at the 99.95th percentile (1/2,000) point based on the estimated prevalence of childhood HCM (2.9 per 100,000 [1/34,483]) to decrease false negatives. Conventional criteria were from guidelines for school-aged children in Japan. Of 11 patients before diagnosis, 2 satisfied conventional criteria in 1st grade; 5 (56%) of the remaining 9 patients fulfilled 2 voltage criteria (R wave in limb-lead I [RI]+S wave in lead V3 [SV3] and R wave in lead V3 [RV3]+SV3). Robustness analysis for sensitivity showed RV3+SV3 was superior to RI+SV3. For all patients after diagnosis, RI+SV4 was the main candidate. However, conventional criteria were more useful than voltage criteria.

    Conclusions:Early HCM prediction was possible using RV3+SV3 in >50% of patients in 1st grade. Voltage criteria may help diagnose prediagnostic or early HCM, and prevent tragic accidents, although further prospective studies are required.

  • Tomotsugu Seki, Hironobu Tokumasu, Hiroyuki Tanaka, Harumi Katoh, Koji ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0483
    Published: October 06, 2021
    [Advance publication] Released: October 06, 2021
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    Background:The appropriateness of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) lesions has rarely been investigated.

    Methods and Results:The Japanese CTO-PCI Expert Registry enrolled consecutive patients undergoing CTO-PCI carried out by highly experienced Japanese CTO specialists who performed more than 50 CTO-PCIs per year and 300 CTO-PCIs in total. This study included patients undergoing CTO-PCI between January 2014 and December 2019. The appropriateness, trends, and differences among the procedures performed by the operators using the 2017 appropriate use criteria were analyzed. Furthermore, we performed a logistic regression analysis to assess whether the appropriateness was associated with in-hospital major adverse cardiovascular and cerebrovascular events (MACCE). Of the 5,062 patients who underwent CTO-PCI, 4,309 (85.1%) patients who did not undergo the non-invasive stress test were classified as having no myocardial ischemia. Of the total cases, 3,150 (62.2%) were rated as “may be appropriate,” and 642 (12.7%) as “rarely appropriate” CTO-PCI cases. The sensitivity analyses showed that the number (%) of “may be appropriate” ranged from 4,125 (57.8%) to 4,744 (66.4%) and the number of “rarely appropriate” ranged from 843 (11.8%) to 970 (13.6%) among best and worst scenarios.

    Conclusions:In a large Japanese CTO-PCI registry, approximately 13% of CTO-PCI procedures were classified as “rarely appropriate”. Substantial efforts would be required to decrease the number of “rarely appropriate” CTO-PCI procedures.

  • Yoshimitsu Soga, Osamu Iida, Masahiko Fujihara, Daizo Kawasaki, Shiger ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0491
    Published: October 06, 2021
    [Advance publication] Released: October 06, 2021
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    Supplementary material

    Background:To confirm the safety and efficacy of the IN.PACT Admiral drug-coated balloon (DCB) based on the indication approved by the Pharmaceuticals and Medical Devices Agency Japan in real-world patients with femoropopliteal artery disease.

    Methods and Results:IN.PACT PMS Japan was a prospective, multicenter, single-arm, post-market surveillance (PMS) study conducted in Japan that enrolled 304 participants (mean age 75.3±7.9 years). The primary endpoint was primary patency at 6 months following the index procedure, defined as freedom from clinically driven target lesion revascularization (CD-TLR) and freedom from restenosis as determined by duplex ultrasound (DUS) peak systolic velocity ratio (PSVR) ≤2.4 (assessed by the independent DUS core laboratory). Secondary endpoints included acute outcomes, primary patency at 12 months post-index procedure, freedom from CD-TLR, and major adverse events at 12 months. The mean lesion length was 97.81±58.97 mm. The primary endpoint, 6-month primary patency, was 91.3% (240/263). Kaplan-Meier estimates of primary patency and freedom from CD-TLR through 12 months were 91.5% and 94.1%, respectively. The CD-TLR rate was 5.8% (14/240) with low rates of thrombosis (0.8%) and target limb amputation (0.4%) at 12 months.

    Conclusions:The results of this real-world PMS study were consistent with outcomes from previous IN.PACT DCB studies, confirming the safety and efficacy of the IN.PACT Admiral DCB for broader use in patients seen in everyday practice.

  • Tomohiko Taniguchi, Hideo Chihara, Yuji Agawa, Taketo Hatano, Kenichi ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-21-0678
    Published: October 05, 2021
    [Advance publication] Released: October 05, 2021
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  • Tatsuya Kokawa, Hiroyuki Yamamoto, Mitsuaki Itoh, Akira Shimane, Hiroy ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-21-0750
    Published: October 05, 2021
    [Advance publication] Released: October 05, 2021
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  • Teruhiko Imamura, Nikhil Narang, Mitsuo Sobajima, Shuhei Tanaka, Ryuic ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0573
    Published: October 01, 2021
    [Advance publication] Released: October 01, 2021
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    Supplementary material

    Background:Coexistent pulmonary hypertension with severe aortic stenosis confers a greater risk of mortality for patients undergoing transcatheter aortic valve replacement (TAVR). In this patient population, the impact of significant decoupling between pulmonary artery diastolic and pulmonary capillary wedge, as it relates to clinical risk, remained uncertain.

    Methods and Results:Patients with severe aortic stenosis who underwent TAVR and completed pre-procedural and post-procedural invasive hemodynamic assessments with right heart catheterization were retrospectively assessed. The impact of post-TAVR decoupling, defined as a pressure difference ≥3 mmHg, on 2-year all-cause mortality or risk of heart failure admission was analyzed. Among 77 included patients (median age 86 years, 23 men), 16 had post-TAVR decoupling. The existence of post-TAVR decoupling was associated with a higher cumulative incidence of the primary endpoint (44% vs. 7%, P=0.001), with an adjusted hazard ratio of 5.87 (95% confidence interval 1.58–21.9, P=0.008).

    Conclusions:A greater risk of worse outcomes in those with post-TAVR decoupling was observed. A therapeutic strategy for post-TAVR decoupling and its clinical implication need to be created and investigated in the future.

  • Masaru Ishida, Takenori Ishisone, Takumi Kimura, Yoshihiro Morino
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-21-0628
    Published: October 01, 2021
    [Advance publication] Released: October 01, 2021
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    Supplementary material
  • Shintaro Sakaguchi, Naoki Fujimoto, Kazuhide Ichikawa, Daisuke Izumi, ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-21-0683
    Published: September 30, 2021
    [Advance publication] Released: September 30, 2021
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  • Hiroyuki Tsutsui, Tomomi Ide, Hiroshi Ito, Yasuki Kihara, Koichiro Kin ...
    Type: JCS GUIDELINES
    Article ID: CJ-21-0431
    Published: September 29, 2021
    [Advance publication] Released: September 29, 2021
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  • Daichi Yamashita, Yuichi Saito, Takanori Sato, Tadahiro Matsumoto, Kan ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0556
    Published: September 29, 2021
    [Advance publication] Released: September 29, 2021
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    Supplementary material

    Background:The PARIS and CREDO-Kyoto risk scores were developed to identify patients at risks of thrombotic and bleeding events individually after percutaneous coronary intervention (PCI). However, these scores have not been well validated in different cohorts.

    Methods and Results:This 2-center registry enrolled 905 patients with acute myocardial infarction (MI) undergoing primary PCI. Patients were divided into 3 groups according to the PARIS and CREDO-Kyoto thrombotic and bleeding risk scores. The study endpoints included ischemic (cardiovascular death, recurrent MI, and ischemic stroke) and major bleeding events. Of 905 patients, 230 (25%) and 219 (24%) had high thrombotic and bleeding risks, respectively, with the PARIS scores, compared with 78 (9%) and 50 (6%) patients, respectively, with the CREDO-Kyoto scores. According to the 2 scores, >50% of patients with high bleeding risk had concomitant high thrombotic risk. During the mean follow-up period of 714 days, 163 (18.0%) and 95 (10.5%) patients experienced ischemic and bleeding events, respectively. Both PARIS and CREDO-Kyoto scores were significantly associated with ischemic and bleeding events after primary PCI. For ischemic events, the CREDO-Kyoto rather than PARIS thrombotic risk score had better diagnostic ability.

    Conclusions:In the present Japanese cohort of acute MI patients undergoing contemporary primary PCI, the PARIS and CREDO-Kyoto thrombotic and bleeding risk scores were discriminative for predicting ischemic and bleeding events.

  • Koichi Inoue, Tsuyoshi Mishima, Yasunori Ueda
    Type: EDITORIAL
    Article ID: CJ-21-0710
    Published: September 29, 2021
    [Advance publication] Released: September 29, 2021
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  • Hiroki Mori, Tadahiro Yoshikawa, Hitomi Kimura, Hiroshi Ono, Hitoshi K ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-20-1239
    Published: September 28, 2021
    [Advance publication] Released: September 28, 2021
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    Background:There has been no nationwide survey on the prognosis of pediatric dilated cardiomyopathy (DCM) in Japan. Therefore, we designed this retrospective multicenter study to investigate the long-term survival rate in pediatric patients with DCM in Japan.

    Methods and Results:In this multicenter retrospective observational study, data were reviewed for 106 patients aged <18 years who had been diagnosed with DCM at any 1 of 18 Japanese institutions between 1990 and 2014. The median age at diagnosis was 2.0 years and the median duration of observation was 3.3 years. Most DCM patients were diagnosed because of symptoms of heart failure. On echocardiography, the median left ventricular end-diastolic dimension z score was 5.4 and fractional shortening was 0.10. Freedom from death or transplantation rates at 1, 3, 5, 10, and 20 years after diagnosis were 76%, 66%, 64%, 58%, and 43%, respectively. Freedom from death rates at 1, 5, 10, and 20 years after diagnosis were 81%, 75%, 72%, and 53%, respectively. The incidence of heart transplantation at 1, 5, 10, and 20 years after diagnosis was 6%, 15%, 20%, and 20%, respectively, suggesting that only 15% of patients in Japan underwent heart transplantation within 5 years of diagnosis.

    Conclusions:In Japan, the prognosis of pediatric DCM is poor and the rate of heart transplantation is low.

  • Pengfei Yue, Zhian Chen, Ziqian Xu, Yucheng Chen
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-21-0689
    Published: September 28, 2021
    [Advance publication] Released: September 28, 2021
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  • Atsushi Kobori, Yasuhiro Sasaki, Misun Pak, Masahiro Ishikura, Ryosuke ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0608
    Published: September 25, 2021
    [Advance publication] Released: September 25, 2021
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    Background:Outcomes of cryoballoon ablation for persistent atrial fibrillation (AF) are unclear, especially in Japanese patients, so the effectiveness and safety of cryoballoon ablation in clinical practice were retrospectively compared with those of contact force-sensing radiofrequency (CFRF) ablation including the high-power protocol.

    Methods and Results:Consecutive patients with persistent AF were reviewed, and 253 and 265 patients who underwent cryoballoon and CFRF ablation, respectively, were enrolled. The primary endpoint was atrial arrhythmia recurrence. The secondary endpoints were periprocedural complications and repeat ablation. The rate of additional left atrial (LA) ablation after pulmonary vein isolation (PVI) was similar between groups (68.8% cryoballoon vs. 74.0% CFRF, P=0.19). Freedom from atrial arrhythmia recurrence was comparable between groups over a follow-up of 25.5±12.5 months (72.3% cryoballoon vs. 69.8% CFRF; adjusted hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.59–1.21, P=0.36). Outcomes were similar in the subgroups of PVI alone and PVI plus additional LA ablation. LA posterior wall isolation, absence of defragmentation, and low creatine clearance, but not catheter selection, were associated with the primary endpoint. Periprocedural complications (adjusted HR 0.73, 95% CI 0.34–1.54, P=0.41) and repeat ablation (adjusted HR 1.11, 95% CI 0.71–1.74, P=0.64) were similar for both procedures.

    Conclusions:Cryoballoon ablation for persistent AF in Japanese clinical practice had acceptable outcomes comparable to those of advanced CFRF ablation.

  • Shigetoyo Kogaki
    Type: EDITORIAL
    Article ID: CJ-21-0730
    Published: September 25, 2021
    [Advance publication] Released: September 25, 2021
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  • Masahiro Natsuaki, Takeshi Kimura
    Type: REVIEW
    Article ID: CJ-21-0751
    Published: September 23, 2021
    [Advance publication] Released: September 23, 2021
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    Optimal antiplatelet therapy after percutaneous coronary intervention (PCI) has been changed in parallel with the improvements of coronary stent and antiplatelet therapy. Over the past 25 years, dual antiplatelet therapy (DAPT) with aspirin plus P2Y12inhibitor has been the standard of care used after coronary stent implantation. First-generation drug-eluting stent (DES) appeared to increase the risk of late stent thrombosis, and duration of DAPT was prolonged to 12 months. DAPT duration up to 12 months was the dominant strategy after DES implantation in the subsequent >10 years, although there was no dedicated randomized controlled trial supporting this recommendation. The current recommendation of DAPT duration is getting shorter due to the development of new-generation DES, use of a P2Y12inhibitor as a monotherapy, and the increasing prevalence of high-bleeding risk patients. Furthermore, an aspirin-free strategy is now emerging as one of the novel strategies of antiplatelet therapy after PCI. This review gives an overview of the history of antiplatelet therapy and provides current and future perspectives on antiplatelet therapy after PCI.

  • Shunpei Horii, Hirotaka Yada, Kei Ito, Kazuhiro Tsujita, Ayumu Osaki, ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-20-1286
    Published: September 17, 2021
    [Advance publication] Released: September 17, 2021
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    Supplementary material

    Background:There is a gradual progression from paroxysmal to persistent atrial fibrillation (AF) in humans. To elucidate the mechanism involved, the creation of an artificial atrial substrate to persist AF in mice was attempted.

    Methods and Results:This study used wild type (WT) mice, but it is difficult to induce AF in them. A novel antegrade perfusion method from the left ventricle (LV) to enlarge both atria for artificial atrial modification was proposed in this study. Short duration AF was induced by burst pacing under this method. Optical mapping analysis revealed non-sustained focal type and meandering spiral reentrants after short duration AF. A tiny artificial substrate (~1.2 mm in diameter) was added in by laser irradiation to create a critical atrial arrhythmogenic substrate. Burst pacing was performed in a non-laser group (n=8), a circular-shape laser group (n=8), and a wedge-shaped dent laser group (n=8). We defined AF and atrial tachycardia (AT) as atrial arrhythmia (AA). Long-lasting AA was defined as lasting for ≥30 min. Long-lasting AA was observed in 0/8, 0/8, and 6/8 (75%) mice in each group. Optical mapping analysis revealed that the mechanism was AT with a stationary rotor around the irradiated margin.

    Conclusions:Regrettably, this study failed to reproduce persistent AF, but succeeded in creating an arrhythmic substrate that causes sustained AT in WT mice.

  • Stefania Angela Di Fusco, Antonella Spinelli, Lorenzo Castello, Gaetan ...
    Type: REVIEW
    Article ID: CJ-21-0459
    Published: September 17, 2021
    [Advance publication] Released: September 17, 2021
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    Growing evidence has shown a bidirectional link between the cardiologic and oncologic fields. Several investigations support the role of unhealthy behaviors as pathogenic factors of both cardiovascular disease and cancer. We report epidemiological and research findings on the pathophysiological mechanisms linking unhealthy lifestyle to cardiovascular disease and cancer. For each unhealthy behavior, we also discuss the role of preventive measures able to affect both cardiovascular disease and cancer occurrence and progression.

  • Satoshi Katano, Toshiyuki Yano, Katsuhiko Ohori, Hidemichi Kouzu, Ryoh ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0584
    Published: September 17, 2021
    [Advance publication] Released: September 17, 2021
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    Supplementary material

    Background:A strategy to predict mortality in elderly heart failure (HF) patients has not been established.

    Methods and Results:We retrospectively enrolled 413 HF patients aged ≥65 years (mean age 78 years) who had received comprehensive cardiac rehabilitation (CR) during hospitalization. Basic activities of daily life were assessed before discharge using the Barthel index (BI). Of 413 HF patients, 116 (28%) died during a median follow-up period of 1.90 years (interquartile range 1.20–3.23 years). An adjusted dose-dependent association analysis showed that the hazard ratio (HR) of mortality increased in an almost linear manner as the BI score decreased, and that a BI score of 85 corresponded to an HR of 1.0. Kaplan-Meier survival curves showed that the survival rate was lower for patients with a low BI (<85) than for those with a high BI (≥85; 65% vs. 74%, respectively; P=0.007). In multivariate Cox regression analyses, low BI was independently associated with higher mortality after adjusting for predictors, including B-type natriuretic peptide. Inclusion of the BI into the adjusted model improved the accuracy of the prediction of mortality.

    Conclusions:A BI score <85 at the time of discharge is associated with increased mortality independent of known prognostic markers, and achieving functional status with a BI score ≥85 by comprehensive CR during hospitalization may contribute to favorable outcomes in elderly HF patients.

  • Yosuke Hirabayashi, Ryuji Okamoto, Shoko Miura, Chisa Inoue, Mei Uemur ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-21-0653
    Published: September 17, 2021
    [Advance publication] Released: September 17, 2021
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    Supplementary material
  • Kenichi Watanabe, Hiroshi Suzuki, Meizi Jiang, Shinya Tsukano, Satoshi ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-20-1271
    Published: September 16, 2021
    [Advance publication] Released: September 16, 2021
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    Background:Intimal smooth muscle cells (SMCs) play an important role in the vasculitis caused by Kawasaki disease (KD). Lipoprotein receptor 11 (LR11) is a member of the low-density lipoprotein receptor family, which is expressed markedly in intimal vascular SMCs and secreted in a soluble form (sLR11). sLR11 has been recently identified as a potential vascular lesion biomarker. sLR11 is reportedly elevated in patients with coronary artery lesions long after KD, but there is no description of sLR11 in acute KD. Our aim was to determine the sLR11 dynamics in acute KD and to assess its usefulness as a biomarker.

    Methods and Results:106 acute KD patients and 18 age-matched afebrile controls were enrolled. KD patients were classified into the following subgroups: intravenous immunoglobulin (IVIG) responders (n=85) and non-responders (n=21). Serum sLR11 levels before IVIG therapy were higher in non-responders (median, 19.6 ng/mL; interquartile range [IQR], 13.0–24.9 ng/mL) than in controls (11.9 ng/mL, 10.4–14.9 ng/mL, P<0.01) or responders (14.3 ng/mL, 11.7–16.5 ng/mL, P<0.01). Using a cutoff of >17.5 ng/mL, non-responders to initial IVIG therapy were identified with 66.7% sensitivity and 78.8% specificity.

    Conclusions:sLR11 can reflect the state of acute KD and might be a biomarker for patient response to IVIG therapy.

  • Masahiro Natsuaki, Takeshi Morimoto, Hiroki Shiomi, Ko Yamamoto, Kyohe ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0526
    Published: September 16, 2021
    [Advance publication] Released: September 16, 2021
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    Supplementary material

    Background:Optimal intensity is unclear for P2Y12receptor blocker therapy after percutaneous coronary intervention (PCI) in real-world clinical practice.

    Methods and Results:From the CREDO-Kyoto Registry, the current study population consisted of 25,419 patients (Cohort-2: n=12,161 and Cohort-3: n=13,258) who underwent their first PCI. P2Y12receptor blocker therapies were reduced dose of ticlopidine (200 mg/day), and global dose of clopidogrel (75 mg/day) in 87.7% and 94.8% of patients in Cohort-2 and Cohort-3, respectively. Cumulative 3-year incidence of GUSTO moderate/severe bleeding was significantly higher in Cohort-3 than in Cohort-2 (12.1% and 9.0%, P<0.0001). After adjusting 17 demographic factors and 9 management factors potentially related to the bleeding events other than the type of P2Y12receptor blocker, the higher bleeding risk in Cohort-3 relative to Cohort-2 remained significant (hazard ratio (HR): 1.52 95% confidence interval (CI) 1.37–1.68, P<0.0001). Cohort-3 compared with Cohort-2 was not associated with lower adjusted risk for myocardial infarction/ischemic stroke (HR: 0.96, 95% CI: 0.87–1.06, P=0.44).

    Conclusions:In this historical comparative study, Cohort-3 compared with Cohort-2 was associated with excess bleeding risk, which might be at least partly explained by the difference in P2Y12receptor blockers.

  • Yasushi Yoshikawa, Yukikatsu Okada, Yutaka Okita, Hitoshi Yaku, Junjir ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0528
    Published: September 15, 2021
    [Advance publication] Released: September 15, 2021
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    Background:This study retrospectively evaluated the long-term patient outcomes and durability of the Mosaic mitral porcine bioprosthesis in the Japan Mosaic valve long-term multicenter study.

    Methods and Results:The medical records of 390 patients who underwent mitral valve replacement with the Mosaic bioprosthesis at 10 centers in Japan (1999–2014) were reviewed. Patient data were collected using the Research Electronic Data Capture software. Patient survival was determined using the Kaplan-Meier method. Freedom from structural valve deterioration (SVD) and valve-related reoperation and death were determined using actuarial methods. The median (interquartile range [IQR]) age of the cohort was 73 (69–77) years. The median (IQR) follow-up period was 4.83 (1.84–8.26) years. The longest follow-up period was 15.8 years. The 30-day mortality rate was 5.4%. The 12-year actuarial survival rate was 54.1±4.5%, and the freedom from valve-related death was 85.3±3.4%. The freedom from reoperation at 12 years was 74.3±5.7%. The freedom from SVD at 12 years was 81.4±6.6% for patients aged ≥65 years and 71.6±11.1% for those aged <65 years. The median (IQR) mean pressure gradient was 4.1 (3.0–6.0) and 5.6 (4.0–6.7) mmHg at 1 and 10 years, respectively. The median (IQR) effective orifice area was 1.7 (1.4–2.0) and 1.4 (1.2–1.6) cm2at 1 and 10 years, respectively.

    Conclusions:The Mosaic porcine bioprosthesis offered satisfactory long-term outcomes for up to 12 years.

  • Hironori Ishiguchi, Takayuki Okamura, Tadamitsu Nakashima, Shigeki Kob ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-21-0693
    Published: September 15, 2021
    [Advance publication] Released: September 15, 2021
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    Supplementary material
  • Hitoshi Nakaya, Ryuji Okamoto, Kazunori Nagashima, Yuichi Sugino, Yosh ...
    Type: IMAGES IN CARDIOVASCULAR MEDICINE
    Article ID: CJ-21-0700
    Published: September 15, 2021
    [Advance publication] Released: September 15, 2021
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  • Takuya Kishi
    Type: EDITORIAL
    Article ID: CJ-21-0694
    Published: September 14, 2021
    [Advance publication] Released: September 14, 2021
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  • Hidenori Kato, Hiroki Watanabe, Akira Koike, Longmei Wu, Kosuke Hayash ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0381
    Published: September 11, 2021
    [Advance publication] Released: September 11, 2021
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    Supplementary material

    Background:Aiming to establish an effective tool in new cardiac rehabilitation programs, we investigated the use of a lumbar-type hybrid assistive limb (HAL) in patients with heart failure (HF) who had difficulty in walking at the usual speed of healthy subjects (≈80 m/min).

    Methods and Results:We randomly assigned 28 HF patients (age, 73.1±13.8 years) to perform a sit-to-stand exercise with or without HAL. The sit-to-stand exercise was repeated as many times as possible as cardiac rehabilitation therapy over a period of 6–10 days. We measured 5 parameters before and after the completion of cardiac rehabilitation: B-type natriuretic peptide, Short Physical Performance Battery (SPPB), 6-min walking distance (6MWD), 30-s chair-stand test (CS-30), and isometric knee extensor muscle strength. The SPPB and 6MWD were significantly improved, and the CS-30 score was somewhat improved, after the exercise therapy in both the HAL and non-HAL groups. The knee extensor muscle strength improved significantly in the HAL group (0.29±0.11 to 0.35±0.11 kgf/kg, P<0.01), but showed no change in the non-HAL group (0.35±0.11 to 0.35±0.13 kgf/kg, P=0.40).

    Conclusions:The improved knee extensor muscle strength in the HAL group suggests that the lumbar-type HAL may be an effective tool for cardiac rehabilitation in HF patients with frailty, which is a predictor of poor prognosis in HF.

  • Naoki Sato, Shingo Uno, Yumiko Yamasaki, Takahiro Hirano, Seongryul Ki ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0430
    Published: September 11, 2021
    [Advance publication] Released: September 11, 2021
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    Supplementary material

    Background:Tolvaptan is an orally administered aquaretic drug indicated for patients with congestive heart failure (CHF) to remove excess fluid. OPC-61815, a prodrug of tolvaptan with improved water solubility, is considered suitable for intravenous (IV) administration. This Phase II study investigated the OPC-61815 dose that would result in an exposure equivalent to tolvaptan 15 mg.

    Methods and Results:We conducted a multicenter, randomized study in Japanese patients aged 20–85 years with CHF and volume overload despite treatment with diuretics other than vasopressin antagonists. Patients received IV OPC-61815 2 mg (n=13), 4 mg (n=12), 8 mg (n=12), 16 mg (n=11), or oral tolvaptan 15 mg (n=12). The primary endpoint was tolvaptan exposure on treatment Day 1; efficacy and safety were also assessed. Tolvaptan exposure increased in a dose-dependent manner following a single IV administration of OPC-61815; the exposure following an IV dose of OPC-61815 16 mg was similar to that of a tolvaptan 15-mg tablet, with no marked differences in safety or tolerability. OPC-61815 increased urine volume from baseline, resulting in decreased body weight and improved lower limb edema. No notable safety concerns were observed.

    Conclusions:In this first study of OPC-61815 in patients with CHF, exposure following a single IV administration of OPC-61815 16 mg was comparable with a single oral administration of tolvaptan 15 mg, with no safety concerns.

  • Yusuke Kondo, Yoshio Kobayashi
    Type: EDITORIAL
    Article ID: CJ-21-0680
    Published: September 09, 2021
    [Advance publication] Released: September 09, 2021
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  • Tae Yokouchi-Konishi, Keiko Ohta-Ogo, Chizuko A. Kamiya, Tadasu Shiono ...
    Type: ORIGINAL ARTICLE
    Article ID: CJ-21-0133
    Published: September 08, 2021
    [Advance publication] Released: September 08, 2021
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    Background:Pregnant women with a Fontan circulation have a high risk of obstetric complications, such as preterm delivery and small for gestational age (SGA), which may be affected by low blood flow to the placenta and hypoxia. This study investigated placental pathology in a Fontan circulation.

    Methods and Results:Eighteen pregnancies in 11 women with a Fontan circulation were reviewed. Pregnancy outcomes showed 9 miscarriages and 9 live births, with 4 preterm deliveries. Five neonates were SGA (<5th percentile). Eight placentas from live births in 7 women were available for the study. Five placentas had low weight placenta for gestational age, and 7 grossly showed a chronic subchorionic hematoma. Histological examination revealed all placentas had some form of histological hypoxic lesions: maternal vascular malperfusion in 7, fetal vascular malperfusion in 1, and other hypoxia-related lesions in 8. Quantitative analyses, including immunohistochemistry (CD31, CD68, and hypoxia inducible factor-1α antibodies) and Masson’s trichrome staining, were also performed and compared with 5 control placentas. Capillary density and the area of fibrosis were significantly greater in placentas from women with a Fontan circulation than in control placentas.

    Conclusions:Placentas in a Fontan circulation were characterized by a high frequency of low placental weight, chronic subchorionic hematoma, and constant histological hypoxic changes, which could reflect altered maternal cardiac conditions and lead to poor pregnancy outcomes.

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