掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Circulation Society  

DOI： 10.1253/circj.cj-24-0966

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担当区分：責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Cardiomyopathies are a heterogeneous group of heart muscle diseases that can lead to heart failure, arrhythmias, and sudden cardiac death. Traditional animal models and in vitro systems have limitations in replicating the complex pathology of human cardiomyopathies. Induced pluripotent stem cells (iPSCs) offer a transformative platform by enabling the generation of patient-specific cardiomyocytes, thus opening new avenues for disease modeling, drug discovery, and regenerative therapy. This process involves reprogramming somatic cells into iPSCs and subsequently differentiating them into functional cardiomyocytes, which can be characterized using techniques such as electrophysiology, contractility assays, and gene expression profiling. iPSC-derived cardiomyocyte (iPSC-CM) platforms are also being explored for drug screening and personalized medicine, including high-throughput testing for cardiotoxicity and the identification of patient-tailored therapies. While iPSC-CMs already serve as valuable models for understanding disease mechanisms and screening drugs, ongoing advances in maturation and bioengineering are bringing iPSC-based therapies closer to clinical application. Furthermore, the integration of multi-omics approaches and artificial intelligence (AI) is enhancing the predictive power of iPSC models. iPSC-based technologies are paving the way for a new era of personalized cardiology, with the potential to revolutionize the management of cardiomyopathies through patient-specific insights and regenerative strategies.

DOI： 10.3390/ijms26114984

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

Background

Cardiac resynchronization therapy (CRT) is an established treatment for patients with heart failure with dyssynchrony. However, one‐third of patients do not respond positively to it. Recently, multipoint pacing (MPP), which involves pacing from two sites on the left ventricle, has been found to improve symptoms and hemodynamics compared to conventional CRT. An automatic fused atrioventricular (AV) delay that performs fused pacing for intrinsic conduction has also been introduced. However, the combined effect of MPP and fused AV delay on acute hemodynamics is unknown.

Objective

To evaluate the acute hemodynamic effects of MPP and fused AV delay in patients undergoing CRT.

Methods

A pressure wire was delivered to the left ventricle, and dp/dt was compared with single atrial stimulation pacing in 52 patients with various pacing configurations.

Results

Delta dp/dt was greater in MPP than in conventional CRT (10.5 ± 1.0% vs. 8.2 ± 1.0%, p < 0.001) and in fused AV delay than in short AV delay (10.4 ± 0.8% vs. 8.3 ± 1.1, p < 0.001). Hemodynamic parameters significantly most improved with the combination of MPP and fused AV delay. Delta dp/dt was greater in LV pacing than in biventricular (BiV) pacing with MPP and fused AV delay; however, the delta QRS duration was shorter in LV pacing than in BiV pacing. Delta dp/dt and delta QRS duration were negatively correlated. The super‐responder rate was 66%.

Conclusion

Combining MPP and fused AV delay has an additional effect. Shortening the QRS duration can increase the dp/dt, but the estimated line differs between LV and BiV pacing.

DOI： 10.1002/joa3.70085

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1038/s42003-025-08167-9

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その他リンク： https://www.nature.com/articles/s42003-025-08167-9

掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Abstract

Background

Edoxaban, a direct oral anticoagulant (DOAC), is a first-line treatment for venous thromboembolism (VTE) and the suppression of VTE recurrence. In patients with cancer, however, recurrent VTE after DOAC treatment may be more common than in noncancer patients. To evaluate our hypothesis that the anticoagulation effect of edoxaban is lower in VTE patients with cancer than in noncancer patients.

Methods

This study was a prospective, multicenter, observational study including patients treated with edoxaban for VTE in Japan. The primary outcome was the difference in the prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer level at 5 h after initial edoxaban administration between the cancer and noncancer groups. An additional outcome was the longitudinal change in PT and APTT from 5 h to overnight after edoxaban administration. The incidence of adverse events was further investigated.

Results

PT and APTT at 5 h after initial edoxaban administration were not significantly different between the cancer (n = 84) and noncancer groups (n = 138) (e.g., log-transformed APTT 3.55 vs. 3.55, p = 0.45). However, D-dimer in the cancer groups was significantly greater than that in the noncancer groups (log-transformed 1.83 vs. 1.79, p = 0.009). PT and APTT significantly decreased from 5 h to overnight after edoxaban, but a similar pattern was observed in each group. All adverse events after edoxaban administration were also similar between patients with cancer and noncancer.

Conclusion

PT and APTT after edoxaban administration were similar between VTE patients with cancer and noncancer groups, suggesting that edoxaban has anticoagulation effects on cancer-associated VTE similar to those of noncancer patients.

Trial registration

UMIN000041973; Registration Date: 2020.10.5.

DOI： 10.1186/s12959-025-00720-0

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その他リンク： https://link.springer.com/article/10.1186/s12959-025-00720-0/fulltext.html

掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.amjcard.2024.12.002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The prognostic utility of high-sensitivity cardiac troponin T (hs-cTnT) on clinical outcomes in cardiac sarcoidosis (CS) remains unknown, so we evaluated hs-cTnT in the chronic phase of CS. METHODS AND RESULTS: We enrolled 92 consecutive patients with CS in the chronic phase after medical therapies. Patients were divided into 2 groups according to hs-cTnT level: 0.014 ng/mL: high hs-cTnT (n=37); normal hs-cTnT (n=55). The primary endpoint was cardiac death and the secondary endpoint was cardiac death, ventricular tachyarrhythmias, or hospitalization for heart failure. The mean age of patients was 63±11 years, and 75 received steroid treatment. During a median follow-up of 63 months, there were 9 cardiac deaths: 7 (19%) patients with high hs-cTnT and 2 (4%) patients with normal hs-cTnT. The rate of cardiac death was higher in patients with high hs-cTnT than in those with normal hs-cTnT (log-rank, P<0.01). Cox proportional hazard analysis showed that hs-cTnT was an independent predictor of cardiac death. The events rate was higher in patients with high hs-cTnT than in those with normal hs-cTnT (log-rank, P<0.01): cardiac death, ventricular tachyarrhythmias or hospitalization for heart failure occurred in 24 (65%) patients with high hs-cTnT and 11 (20%) patients with normal hs-cTnT. CONCLUSIONS: Elevated hs-cTnT was linked with adverse outcomes in CS patients, suggesting it is an effective prognostic biomarker.

DOI： 10.1253/circj.CJ-24-0801

PubMed

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担当区分：筆頭著者,　責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Pulmonary hypertension associated with lung diseases and/or hypoxia is classified as group 3 in the clinical classification of pulmonary hypertension. The efficacy of existing selective pulmonary vasodilators for group 3 pulmonary hypertension is still unknown, and it is currently associated with a poor prognosis. The mechanisms by which pulmonary hypertension occurs include hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, a decrease in pulmonary vascular beds, endothelial dysfunction, endothelial-to-mesenchymal transition, mitochondrial dysfunction, oxidative stress, hypoxia-inducible factors (HIFs), inflammation, microRNA, and genetic predisposition. Among these, hypoxic pulmonary vasoconstriction and subsequent pulmonary vascular remodeling are characteristic factors involving the pulmonary vasculature and are the focus of this review. Several factors have been reported to mediate vascular remodeling induced by hypoxic pulmonary vasoconstriction, such as HIF-1α and mechanosensors, including TRP channels. New therapies that target novel molecules, such as mechanoreceptors, to inhibit vascular remodeling are awaited.

DOI： 10.3390/ijms26020835

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掲載種別：研究論文（学術雑誌）   出版者・発行元：BMJ  

Background

Among patients with dilated cardiomyopathy (DCM), myocardial inflammation and fibrosis are risk factors for poor clinical outcomes. Here, we investigated the combined prognostic value of these two factors, as evaluated using myocardial biopsy samples.

Methods

This retrospective and multicentre study included patients with DCM—defined as LVEF of ≤45% and left diastolic diameter of &gt;112% of predicted value, without evidence of secondary or ischaemic cardiomyopathy. In myocardial biopsy samples, inflammatory cells were counted using immunohistochemistry, and Masson’s Trichrome staining was performed to quantify the myocardial fibrosis as collagen area fraction (CAF). Higher myocardial inflammation was defined as leucocytes of ≥14/mm², including ≤4 monocytes/mm², with CD3⁺ T lymphocytes of≥7/mm². Greater myocardial fibrosis was defined as CAF of&gt;5.9% by the Youden’s index. The primary endpoint was cardiac death or left ventricular assist device implantation.

Results

A total of 255 DCM patients were enrolled (average age, 53.1 years; 78% males). Within this cohort, the mean LVEF was 28.0%, mean CAF was 10.7% and median CD3⁺ cell count was 8.3/mm². During the median follow-up period of 2688 days, 46 patients met the primary endpoint. Multivariable Cox proportional hazard analyses revealed that CD3⁺ cell count and CAF were independent determinants of the primary endpoint. Kaplan–Meier analysis showed that patients with both higher myocardial inflammation and greater fibrosis had the worst prognosis (log-rank p&lt;0.001). When myocardial inflammation was graded as one of three degrees: T lymphocytes of &lt;13/mm² (low); 13 of 13.1–23.9/mm² (moderate); and T lymphocytes of ≥24 /mm² (high), patients with moderate inflammation exhibited a superior survival rate when CAF was ≤5.9%, but a worse survival rate when CAF was &gt;5.9%.

Conclusions

Having both biopsy-proven higher myocardial inflammation and greater fibrosis predicted the worst clinical prognosis in patients with DCM.

DOI： 10.1136/openhrt-2025-003250

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jcin.2025.02.014

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.hroo.2024.12.007

Scopus

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1536/ihj.25-105

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jaccas.2025.105347

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Induced pluripotent stem cell (iPSC)-derived biological pacemakers have emerged as an alternative to traditional electronic pacemakers for managing cardiac arrhythmias. While effective, electronic pacemakers face challenges such as device failure, lead complications, and surgical risks, particularly in children. iPSC-derived pacemakers offer a promising solution by mimicking the sinoatrial node’s natural pacemaking function, providing a more physiological approach to rhythm control. These cells can differentiate into cardiomyocytes capable of autonomous electrical activity, integrating into heart tissue. However, challenges such as achieving cellular maturity, long-term functionality, and immune response remain significant barriers to clinical translation. Future research should focus on refining gene-editing techniques, optimizing differentiation, and developing scalable production processes to enhance the safety and effectiveness of these biological pacemakers. With further advancements, iPSC-derived pacemakers could offer a patient-specific, durable alternative for cardiac rhythm management. This review discusses key advancements in differentiation protocols and preclinical studies, demonstrating their potential in treating dysrhythmias.

DOI： 10.3390/cells13242045

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jacasi.2024.09.006

PubMed

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担当区分：責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Heart Journal (Japanese Heart Journal)  

DOI： 10.1536/ihj.24-323

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Circulation Society  

DOI： 10.1253/circj.cj-24-0506

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.hroo.2024.09.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Circulation Society  

DOI： 10.1253/circj.cj-24-0313

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

Aims

Although right ventricular (RV) dysfunction is associated with adverse outcomes in tricuspid regurgitation (TR), the potential role of right atrial (RA) function is unknown. We aimed to investigate the relationship between RA function and clinical outcomes in patients with significant TR.

Methods

This retrospective study included 169 outpatients with moderate or severe TR due to left‐sided heart diseases who underwent transthoracic echocardiography between June 2020 and April 2023 (average age, 75 ± 10 years; male, 40%). Patients with atrial fibrillation were excluded from this study due to the inaccuracy of the evaluation using 2D speckle‐tracking echocardiography. RA function was compared between patients with and without events, which were defined as all‐cause mortality or hospitalization due to heart failure. RA function was calculated as RA global longitudinal strain (RAGLS) with the 2D speckle‐tracking echocardiography.

Results

During a median follow‐up of 13 months, 19 patients had events (all‐cause mortality: 14 cases, hospitalization due to heart failure: 5 cases). RAGLS was lower in patients with events than in those without events (13% ± 10% vs. 18% ± 9%, P = 0.02). When the patients were categorized into two groups [low RAGLS ≤ 16.2% vs. high RAGLS &gt; 16.2%, high RA volume index (RAVI) ≥ 50 mL/m² vs. low RAVI &lt; 50 mL/m²], Kaplan–Meier curves showed that patients with low RAGLS had higher event rates than those with high RAGLS (log‐rank test, P = 0.003). Patients with high RAVI had higher event rates than those with low RAVI (log‐rank test, P &lt; 0.001). In the multivariate Cox regression analysis, low RAGLS (≤16.2%) was significantly associated with events in a model that included RV dysfunction (RV fractional area change ≤ 35%) or high RAVI (≥50 mL/m²) (hazard ratio: 4.55, 95% confidence interval: 1.51–13.71, P &lt; 0.01; hazard ratio: 4.57, 95% confidence interval: 1.52–13.79, P &lt; 0.01, respectively).

Conclusions

RAGLS is associated with all‐cause mortality and hospitalization due to heart failure in patients with significant TR. Our results suggest that RA function is a sensitive marker for identifying the risk stratification of significant TR.

DOI： 10.1002/ehf2.14846

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

UNLABELLED: An 82-year-old man with a secundum atrial septal defect (ASD) underwent transcatheter closure. The patient had a wide area of aortic and superior rim deficiency, with left ventricular diastolic dysfunction and moderate mitral regurgitation. These findings suggested the risk of both cardiac erosion and increased left atrial pressure after closure. To avoid cardiac erosion, a GORE® CARDIOFORM ASD (GCA) occluder (W.L. Gore & Associates, Flagstaff, AZ, USA) was considered an appropriate device in this patient. However, the possibility of excessively high left atrial pressure due to complete defect closure was a concern. Thus, we created a 4.5-mm fenestration using a surgical punch in the fabric membrane of a 44-mm GCA. The device was deployed in an appropriate position, and no significant elevation of pulmonary capillary wedge pressure was observed. One month after the closure, marked improvement in clinical symptoms and continuous flow through the fenestration were observed. This novel fenestration technique may contribute to expansion of the indications for transcatheter ASD closure in patients who require a GCA owing to an anatomically high risk of erosion accompanied by left ventricular diastolic dysfunction. LEARNING OBJECTIVE: In elderly patients with left ventricular diastolic dysfunction, transcatheter atrial septal defect (ASD) closure is difficult because rapid resolution of an ASD shunt can cause an increase in left atrial pressure. Previous reports described the creation of a fenestration in the closure device. The use of a GORE® CARDIOFORM ASD (GCA) occluder can reduce the erosion risk; however, creating a stable fenestration is difficult. We developed a novel technique to create a stable fenestration in a GCA.

DOI： 10.1016/j.jccase.2024.04.001

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1002/ccd.31163

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The prognostic impact of extracardiac sarcoidosis remains unknown in cardiac sarcoidosis (CS). We aimed to evaluate the influence of extracardiac sarcoidosis on clinical outcomes and the effect of continued outpatient visits for screening of cardiac involvement. METHODS: Ninety-nine patients with CS were divided into two groups: patients with systemic CS who had prior extracardiac sarcoidosis, patients with isolated CS who had no prior extracardiac sarcoidosis. Patients with systemic CS were divided according to the continuation of outpatient visits. The endpoint was cardiac death, fatal ventricular arrhythmia, or hospitalization for heart failure. RESULTS: At the time of diagnosing CS, patients with isolated CS had a higher prevalence of high-grade atrioventricular block or fatal ventricular arrhythmia, and left ventricular contractile dysfunction than those with systemic CS. Over a median follow-up of 42 months, cardiac events occurred in 19 (37%) of 52 patients with systemic CS and in 27 (57%) of 47 patients with isolated CS. The event-free survival rate was worse in patients with isolated CS than in those with systemic CS. Cox proportional hazard analysis showed that the absence of prior extracardiac sarcoidosis was an independent predictor of adverse outcomes. Patients with systemic CS who ceased outpatient visits had a lower left ventricular ejection fraction with severe heart failure symptoms and a worse event-free survival rate than those who continued outpatient visits. CONCLUSIONS: The presence of extracardiac sarcoidosis is associated with clinical outcomes. The cessation of screening for cardiac involvement after diagnosing extracardiac sarcoidosis is associated with adverse outcomes.

DOI： 10.1016/j.ijcard.2024.132368

PubMed

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担当区分：責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Diabetes mellitus (DM) is a major risk and prognostic factor for heart failure (HF). Insulin resistance (IR) is an important component of DM, but the relationship between IR and HF prognosis has not yet been established across a wide variety of HF populations. We retrospectively evaluated the relationship between IR and clinical outcomes of HF patients at our hospital between 2017 and 2021. IR was defined as a homeostatic model assessment of IR (HOMA-IR) index ≥ 2.5, calculated from fasting blood glucose and insulin concentrations. The primary outcome was a composite of all-cause death and hospitalisation for HF (HHF). Among 682 patients included in the analyses, 337 (49.4%) had IR. The median age was 70 [interquartile range (IQR): 59–77] years old, and 66% of the patients were men. Among the patients, 41% had a left ventricular ejection fraction below 40%, and 32% had DM. The median follow-up period was 16.5 [IQR: 4.4–37.3] months. IR was independently associated with the primary outcome (HR: 1.91, 95% CI: 1.39–2.62, p &lt; 0.0001), death (hazard ratio [HR]: 1.86, 95% confidence interval [CI]: 1.28–2.83, p &lt; 0.01), and HHF (HR: 1.91, 95% CI: 1.28–2.83, p &lt; 0.01). HOMA-IR is an independent prognostic factor of HF in a wide variety of HF populations.

DOI： 10.3390/nu16121888

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Public Library of Science (PLoS)  

Background

Stem cell research, particularly in the domain of induced pluripotent stem cell (iPSC) technology, has shown significant progress. The integration of artificial intelligence (AI), especially machine learning (ML) and deep learning (DL), has played a pivotal role in refining iPSC classification, monitoring cell functionality, and conducting genetic analysis. These enhancements are broadening the applications of iPSC technology in disease modelling, drug screening, and regenerative medicine. This review aims to explore the role of AI in the advancement of iPSC research.

Methods

In December 2023, data were collected from three electronic databases (PubMed, Web of Science, and Science Direct) to investigate the application of AI technology in iPSC processing.

Results

This systematic scoping review encompassed 79 studies that met the inclusion criteria. The number of research studies in this area has increased over time, with the United States emerging as a leading contributor in this field. AI technologies have been diversely applied in iPSC technology, encompassing the classification of cell types, assessment of disease-specific phenotypes in iPSC-derived cells, and the facilitation of drug screening using iPSC. The precision of AI methodologies has improved significantly in recent years, creating a foundation for future advancements in iPSC-based technologies.

Conclusions

Our review offers insights into the role of AI in regenerative and personalized medicine, highlighting both challenges and opportunities. Although still in its early stages, AI technologies show significant promise in advancing our understanding of disease progression and development, paving the way for future clinical applications.

DOI： 10.1371/journal.pone.0302537

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Patients with severe aortic stenosis (AS) frequently have concomitant aortic regurgitation (AR), but the association between aortic valvular calcification (AVC) and the severity of AR remains unclear.Methods and Results: We retrospectively reviewed patients with severe AS who underwent transthoracic echocardiography and multidetector computed tomography (MDCT) within 1 month. The patients were divided into 3 groups according to the degree of concomitant AR. The association between AVC and the severity of concomitant AR was assessed in patients with severe AS. The study population consisted of 95 patients: 43 men and 52 women with a mean age of 82±7 years. Of the 95 patients with severe AS, 27 had no or trivial AR, 53 had mild AR, and 15 had moderate AR. The AVC score (AVCS) and AVC volume (AVCV) significantly increased as the severity of concomitant AR increased (P=0.014 for both), and similar findings were obtained for the AVCS and AVCV indexes (P=0.004 for both). CONCLUSIONS: The severity of AR correlated with AVCS and AVCV measured by MDCT in patients with severe AS. AVC may cause concomitant AR, leading to worsening of disease condition.

DOI： 10.1253/circj.CJ-22-0746

PubMed

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

Background

Remote monitoring (RM) of cardiac implantable electrical devices (CIEDs) can detect various events early. However, the diagnostic ability of CIEDs has not been sufficient, especially for lead failure. The first notification of lead failure was almost noise events, which were detected as arrhythmia by the CIED. A human must analyze the intracardiac electrogram to accurately detect lead failure. However, the number of arrhythmic events is too large for human analysis. Artificial intelligence (AI) seems to be helpful in the early and accurate detection of lead failure before human analysis.

Objective

To test whether a neural network can be trained to precisely identify noise events in the intracardiac electrogram of RM data.

Methods

We analyzed 21 918 RM data consisting of 12 925 and 1884 Medtronic and Boston Scientific data, respectively. Among these, 153 and 52 Medtronic and Boston Scientific data, respectively, were diagnosed as noise events by human analysis. In Medtronic, 306 events, including 153 noise events and randomly selected 153 out of 12 692 nonnoise events, were analyzed in a five‐fold cross‐validation with a convolutional neural network. The Boston Scientific data were analyzed similarly.

Results

The precision rate, recall rate, F1 score, accuracy rate, and the area under the curve were 85.8 ± 4.0%, 91.6 ± 6.7%, 88.4 ± 2.0%, 88.0 ± 2.0%, and 0.958 ± 0.021 in Medtronic and 88.4 ± 12.8%, 81.0 ± 9.3%, 84.1 ± 8.3%, 84.2 ± 8.3% and 0.928 ± 0.041 in Boston Scientific. Five‐fold cross‐validation with a weighted loss function could increase the recall rate.

Conclusions

AI can accurately detect noise events. AI analysis may be helpful for detecting lead failure events early and accurately.

DOI： 10.1002/joa3.13037

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: A treatment strategy for congenital heart defects with moderate to severe pulmonary arterial hypertension (PAH) has not been established. OBJECTIVES: The purpose of this study was to identify patients in whom a treat and repair strategy was considered and to examine pretreatment variables associated with successful defect repair. METHODS: Patients with atrial or ventricular septal defect and PAH (pulmonary vascular resistance [PVR] ≥ 5 Wood units) eligible for the treat and repair strategy were included. Hemodynamics among pretreatment, pre-repair, and post-defect repair were compared. Clinical outcomes in patients with or without defect repair were also compared. Clinical outcomes included all-cause death, hospitalization for worsening pulmonary hypertension, and lung transplantation. RESULTS: Among 25 eligible for the treat and repair strategy, 20 underwent successful repair (repaired group) and 5 did not have a repair (unrepaired group). In the repaired group, PVR significantly decreased from 9.6 ± 2.6 WU at pretreatment to 5.0 ± 3.4 pre-repair (ß coefficient -4.6 [95% CI: -5.9 to -3.3]). The pulmonary to systemic blood flow ratio (Qp/Qs) increased from 1.5 ± 0.6 at pretreatment to 2.4 ± 1.3 pre-repair (ß coefficient 0.9 [95% CI: 0.4-1.38]). In the unrepaired group, pretreatment PVR decreased with treatment; however, PVR remained elevated. Qp/Qs did not change between pretreatment and post-treatment. The repaired group had a better prognosis than the unrepaired group (HR 0.092 [95% CI: 0.009-0.905]). Pretreatment mean pulmonary artery pressure, PVR, Qp/Qs, and arterial oxygen saturations were associated with undergoing defect repair. CONCLUSIONS: In this small cohort, a treat and repair strategy was successfully used in a significant proportion of the patients with congenital heart defects with moderate to severe PAH.

DOI： 10.1016/j.jacadv.2024.100887

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.ejrad.2024.111354

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Electrical storm (ES) of ventricular tachyarrhythmias (VTAs) is an important cause of sudden death in patients with cardiac sarcoidosis (CS). VTAs in CS are associated with myocardial scarring and inflammation. However, little is known about the risk factors of ES in patients with CS and VTAs. The objective of this study is to clarify the characteristics and risk factors for the development of ES in patients with CS. METHODS: The study population included consecutive 52 patients with CS and sustained VTA. Twenty-five out of 52 patients experienced ES. We evaluated clinical characteristics, imaging modalities, and electrocardiogram (ECG) parameters to determine the risk factors associated with ES. RESULTS: Half of the patients experienced VTAs as the initial symptom of sarcoidosis, and eight patients had ES as the initial VTA episode. There were no differences in cardiac imaging abnormalities between patients with and without ES. Among ECG markers, significant QRS fragmentation (odds ratio [OR]: 7.9, p = .01) and epsilon waves (OR: 12.24, p = .02) were associated with ES. Among the ventricular tachycardia (VT) characteristics, multiple morphologies of monomorphic VTs (OR: 10.9, p < .01), short VT cycle lengths (OR: 12.5, p < .01), and polymorphic VT (OR: 13.5, p < .01) were associated with ES. Bidirectional VTs were detected in 10 patients with ES and one patient without ES. Immunosuppressive therapy relieved ES in some patients. CONCLUSIONS: ES was common in patients with CS and VTAs. Significant depolarization abnormalities that appeared as QRS fragmentation, epsilon waves, and specific VT characteristics were associated with ES.

DOI： 10.1111/jce.16156

PubMed

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12928-023-00956-5

PubMed

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s12928-023-00979-y

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その他リンク： https://link.springer.com/article/10.1007/s12928-023-00979-y/fulltext.html

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Ischemic heart disease (IHD) poses a significant challenge in cardiovascular health, with current treatments showing limited success. Induced pluripotent derived–cardiomyocyte (iPSC-CM) therapy within regenerative medicine offers potential for IHD patients, although its clinical impacts remain uncertain. This study utilizes meta-analysis to assess iPSC-CM outcomes in terms of efficacy and safety in IHD animal model studies. A meta-analysis encompassing PUBMED, ScienceDirect, Web of Science, and the Cochrane Library databases, from inception until October 2023, investigated iPSC therapy effects on cardiac function and safety outcomes. Among 51 eligible studies involving 1012 animals, despite substantial heterogeneity, the iPSC-CM transplantation improved left ventricular ejection fraction (LVEF) by 8.23% (95% CI, 7.15 to 9.32%; p &lt; 0.001) compared to control groups. Additionally, cell-based treatment reduced the left ventricle fibrosis area and showed a tendency to reduce left ventricular end-systolic volume (LVESV) and end-diastolic volume (LVEDV). No significant differences emerged in mortality and arrhythmia risk between iPSC-CM treatment and control groups. In conclusion, this meta-analysis indicates iPSC-CM therapy’s promise as a safe and beneficial intervention for enhancing heart function in IHD. However, due to observed heterogeneity, the efficacy of this treatment must be further explored through large randomized controlled trials based on rigorous research design.

DOI： 10.3390/ijms25020987

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記述言語：英語  

[This corrects the article DOI: 10.3389/fcvm.2023.1212882.].

DOI： 10.3389/fcvm.2024.1369831

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掲載種別：研究論文（学術雑誌）  

DOI： 10.3389/fcvm.2024.1369831

Scopus

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/pace.14871

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.amjcard.2023.07.125

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Frontiers Media SA  

Introduction

Transplantation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is a promising treatment for heart failure. Information on long-term cell engraftment after transplantation is clinically important. However, clinically applicable evaluation methods have not yet been established.

Methods

In this study, to noninvasively assess transplanted cell engraftment, human SLC5A5, which encodes a sodium/iodide symporter (NIS) that transports radioactive tracers such as ¹²⁵I, ¹⁸F-tetrafluoroborate (TFB), and ^99mTc-pertechnetate (^99mTcO₄⁻), was transduced into human induced pluripotent stem cells (iPSCs), and nuclear medicine imaging was used to track engrafted human iPSC-CMs.

Results

To evaluate the pluripotency of NIS-expressing human iPSCs, they were subcutaneously transplanted into immunodeficient rats. Teratomas were detected by ^99mTcO₄⁻ single photon emission computed tomography (SPECT/CT) imaging. NIS expression and the uptake ability of ¹²⁵I were maintained in purified human iPSC-CMs. NIS-expressing human iPSC-CMs transplanted into immunodeficient rats could be detected over time using ^99mTcO₄⁻ SPECT/CT imaging. Unexpectedly, NIS expression affected cell proliferation of human iPSCs and iPSC-derived cells.

Discussion

Such functionally designed iPSC-CMs have potential clinical applications as a noninvasive method of grafted cell evaluation, but further studies are needed to determine the effects of NIS transduction on cellular characteristics and functions.

DOI： 10.3389/fcvm.2023.1261330

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The metabolic state of pulmonary artery smooth muscle cells (PASMCs) from patients with pulmonary arterial hypertension (PAH) is not well understood. In this study, we examined the balance between glycolysis and mitochondrial respiration in non-PAH-PASMCs and PAH-PASMCs under normoxia and hypoxia. METHODS: We investigated the enzymes involved in glycolysis and mitochondrial respiration, and studied the two major energy-yielding pathways (glycolysis and mitochondrial respiration) by measuring extracellular acidification rate (ECAR) and cellular oxygen consumption rate (OCR) using the Seahorse extracellular flux technology. RESULTS: Under both normoxia and hypoxia, the mRNA and protein levels of pyruvate dehydrogenase kinase 1 and pyruvate dehydrogenase were increased in PAH-PASMCs compared with non-PAH-PASMCs. The mRNA and protein levels of lactate dehydrogenase, as well as the intracellular lactate concentration, were also increased in PAH-PASMCs compared with non-PAH-PASMCs under normoxia. However, these were not significantly increased in PAH-PASMCs compared with non-PAH-PASMCs under hypoxia. Under normoxia, ATP production was significantly lower in PAH-PASMCs (59 ± 5 pmol/min) than in non-PAH-PASMCs (70 ± 10 pmol/min). On the other hand, ATP production was significantly higher in PAH-PASMCs (31 ± 5 pmol/min) than in non-PAH-PASMCs (14 ± 3 pmol/min) under hypoxia. CONCLUSIONS: There is an underlying change in the metabolic strategy to generate ATP production under the challenge of hypoxia.

DOI： 10.3390/jcm12155028

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Various types of arrhythmia are observed in patients with cardiac amyloidosis, but the prevalence of arrhythmia has not been fully investigated. This study investigated the prevalence and treatment of arrhythmias in patients with cardiac amyloidosis before the introduction of new agents for amyloidosis, such as tafamidis. Methods and Results: Of 53 patients who were histologically diagnosed with cardiac amyloidosis at 10 centers in western Japan between 2009 and 2021, 43 who were diagnosed on the basis of immunohistochemical staining were evaluated in this study. Of these 43 patients, 13 had immunoglobulin light-chain (AL) amyloidosis and 30 had transthyretin (ATTR) amyloidosis; further, 27 had atrial tachyarrhythmia, 13 had ventricular tachyarrhythmia, and 17 had bradyarrhythmia. Atrial fibrillation (AF) was the most common arrhythmia in patients with cardiac amyloidosis (n=24; 55.8%), especially among those with ATTR amyloidosis (70.0% of ATTR vs. 23.1% of AL). Eleven (25.6%) patients were treated with a cardiac implantable device. All 3 patients with pacemakers were alive at the last follow-up (median 76.7 months; interquartile range [IQR] 4.8-146.4 months). Of the 8 patients who underwent AF ablation, there was no recurrence in 6 (75%) after a median of 39.3 months (IQR 19.8-59.3 months). Conclusions: The prevalence of various arrhythmias was high in patients with cardiac amyloidosis. AF occurred most frequently in patients with cardiac amyloidosis, especially among patients with ATTR.

DOI： 10.1253/circrep.CR-23-0022

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：(一社)日本循環器学会  

DOI： 10.1002/pul2.12286

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Circulation Society  

DOI： 10.1253/circrep.cr-23-0034

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担当区分：筆頭著者,　責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Heart Journal (Japanese Heart Journal)  

DOI： 10.1536/ihj.22-752

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担当区分：責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Heart Journal (Japanese Heart Journal)  

DOI： 10.1536/ihj.22-578

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background The appearance of complete right bundle-branch block (CRBBB) in Brugada syndrome (BrS) is associated with an increased risk of ventricular fibrillation. The pathophysiological mechanism of CRBBB in patients with BrS has not been well established. We aimed to clarify the significance of a conduction delay zone associated with arrhythmias on CRBBB using body surface mapping in patients with BrS. Methods and Results Body surface mapping was recorded in 11 patients with BrS and 8 control patients both with CRBBB. CRBBB in control patients was transiently exhibited by unintentional catheter manipulation (proximal RBBB). Ventricular activation time maps were constructed for both of the groups. We divided the anterior chest into 4 areas (inferolateral right ventricle [RV], RV outflow tract [RVOT], intraventricular septum, and left ventricle) and compared activation patterns between the 2 groups. Excitation propagated to the RV from the left ventricle through the intraventricular septum with activation delay in the entire RV in the control group (proximal RBBB pattern). In 7 patients with BrS, excitation propagated from the inferolateral RV to the RVOT with significant regional activation delay. The remaining 4 patients with BrS showed a proximal RBBB pattern with the RVOT activation delay. The ventricular activation time in the inferolateral RV was significantly shorter in patients with BrS without a proximal RBBB pattern than in control patients. Conclusions The CRBBB morphology in patients with BrS consisted of 2 mechanisms: (1) significantly delayed conduction in the RVOT and (2) proximal RBBB with RVOT conduction delay. Significant RVOT conduction delay without proximal RBBB resulted in CRBBB morphology in patients with BrS.

DOI： 10.1161/JAHA.122.028706

PubMed

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掲載種別：研究論文（学術雑誌）   出版者・発行元：American College of Physicians  

DOI： 10.7326/aimcc.2022.1003

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Circulation Society  

DOI： 10.1253/circj.cj-22-0696

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Amyloidosis is a large group of diseases that are caused by the deposition of insoluble amyloid fibrils formed by misfolded soluble proteins in organs or tissues [...]

DOI： 10.3390/ijms24086980

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：International Heart Journal (Japanese Heart Journal)  

DOI： 10.1536/ihj.22-574

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担当区分：責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

Aims

Heart failure with preserved ejection fraction (HFpEF), which is caused by wide various conditions, has become a major public health problem. Transthyretin amyloid cardiomyopathy (ATTR‐CM), which is thought to be an underdiagnosed disease, can cause HFpEF. Non‐invasive diagnosis using ^99mTechnetium (Tc)‐pyrophosphate (PYP) scintigraphy enables accurate diagnosis of ATTR‐CM. The aim of this study was to clarify the prevalence and characteristics of ATTR‐CM among Japanese patients with HFpEF.

Methods and results

This study was a multicentre, prospective, observational study conducted in Japan. We enrolled 373 patients with HFpEF [left ventricular (LV) ejection fraction ≥50%] aged ≥65 years who were admitted to the department of cardiology from September 2018 to January 2022. A ^99mTc‐PYP scintigraphy scan was performed during admission in all eligible patients. Cardiac ^99mTc‐PYP retention was graded according to a previously reported visual scale ranging from 0 to 3 points. The scan was considered positive when it revealed moderate‐to‐severe ^99mTc‐PYP uptake (Grade 2–3) in both ventricles. Patients were divided into ATTR‐CM and non‐ATTR‐CM patients according to positive (Grade 2–3) or negative (Grade 0–1) 99mTc‐PYP scintigraphy, respectively. Medical history, blood tests, electrocardiogram, echocardiography, and magnetic resonance imaging in the two groups of patients were compared. Among the 373 patients with HFpEF, 53 patients (14.2%; 95% confidence interval: 10.7–17.7) showed positive uptake on ^99mTc‐PYP scintigraphy. An endomyocardial biopsy was performed in 32 patients and confirmed amyloidosis in all cases. There were no significant differences between the two groups in age, severity of heart failure as assessed by the New York Heart Association (NYHA) functional classification, renal function values, left ventricular ejection fraction, and tricuspid regurgitant pressure gradient (ATTR‐CM, n = 53 vs. non‐ATTR‐CM, n = 320). Patients in the ATTR‐CM group had a higher N‐terminal pro‐brain natriuretic peptide level [2314 (1081–3398) vs. 900 (415–1828), P &lt; 0.001], higher sensitive troponin T level (0.074 ± 0.049 vs. 0.035 ± 0.038, P &lt; 0.001), and higher mean LV maximal wall thickness [12.5 (11–14) vs. 10.5 (9.5–11.5), P &lt; 0.001].

Conclusions

ATTR‐CM is an underdiagnosed disease with a significant prevalence in Japanese patients with HFpEF. This study showed that results of examinations for ATTR‐CM patients appear to be worse than those for non‐ATTR‐CM patients, but clinical severities of heart failure as assessed by the NYHA functional classification are similar in ATTR‐CM and non‐ATTR‐CM patients, and the clinical overlap between ATTR‐CM and non‐ATTR‐CM is high.

DOI： 10.1002/ehf2.14364

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Ovid Technologies (Wolters Kluwer Health)  

Background

<p lang="en">Despite the impact of heat exposure caused by global warming, few studies have investigated the hourly effects of heat exposure and the risk of cardiovascular disease (CVD) in the elderly. We examined the associations between short‐term heat exposure and the risk of CVD in the elderly in Japan and evaluated possible effect‐measure modifications by rainy seasons that occur in East Asia.

</p> Methods and Results

<p lang="en">We conducted a time‐stratified case–crossover study. The study included 6527 residents in Okayama City, Japan, aged ≥65 years who were transported to emergency hospitals between 2012 and 2019 for the onset of CVD during and a few months after the rainy seasons. We examined the linear associations between temperature and CVD‐related emergency calls for each year and for hourly preceding intervals before the emergency call during the most relevant months. Heat exposure during 1 month after the end of the rainy season was associated with CVD risk; the odds ratio (OR) for a 1° C increase in temperature was 1.34 (95% CI, 1.29–1.40). When we further explored the nonlinear association by using the natural cubic spline model, we found a J‐shaped relationship. Exposures 0 to 6 hours before the case event (preceding intervals 0–6 hours) were associated with CVD risk, particularly for the preceding interval 0 to 1 hour (OR, 1.33 [95% CI, 1.28–1.39]). For longer periods, the highest risk was at preceding intervals 0 to 23 hours (OR, 1.40 [95% CI, 1.34–1.46]).

</p> Conclusions

<p lang="en">Elderly individuals may be more susceptible to CVD after heat exposure during the month after the rainy season. As shown by finer temporal resolution analyses, short‐term exposure to increasing temperature can trigger CVD onset.

</p>

DOI： 10.1161/jaha.122.027046

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cardiovascular diseases and liver diseases are closely related. Non-alcoholic fatty liver disease has the same risk factors as those for atherosclerotic cardiovascular disease and may also be a risk factor for atherosclerotic cardiovascular disease on its own. Heart failure causes liver fibrosis, and liver fibrosis results in worsened cardiac preload and congestion. Although some previous reports regard the association between cardiovascular diseases and liver disease, the management strategy for liver disease in patients with cardiovascular diseases is not still established. This review summarized the association between cardiovascular diseases and liver disease. In patients with non-alcoholic fatty liver disease, the degree of liver fibrosis progresses with worsening cardiovascular prognosis. In patients with heart failure, liver fibrosis could be a prognostic marker. Liver stiffness assessed with shear wave elastography, the fibrosis-4 index, and non-alcoholic fatty liver disease fibrosis score is associated with both liver fibrosis in patients with liver diseases and worse prognosis in patients with heart failure. With the current population ageing, the importance of management for cardiovascular diseases and liver disease has been increasing. However, whether management and interventions for liver disease improve the prognosis of cardiovascular diseases has not been fully understood. Future investigations are needed.

DOI： 10.3390/nu15030748

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Exercise therapy following endovascular treatment (EVT) is important for patients with peripheral artery disease (PAD); however, continuous exercise therapy is difficult to be performed in clinical practice. This study aimed to investigate the association between the implementation of home-based exercise using pedometers after EVT and 1-year clinical outcomes. METHODS: This multicenter observational prospective cohort registry included patients with PAD complaining of intermittent claudication who underwent EVT for aortoiliac and/or femoropopliteal artery lesions between January 2016 and March 2019. Patients were instructed to perform home-based exercises using a specific pedometer after EVT. The study population was divided into good and poor recording groups according to the frequency of the pedometer measurements. The good recording group was defined as those who completed ≥50 % of the prescribed daily pedometer recording during the follow-up period. The poor recording group was defined as those with an inability to use a pedometer and/or who completed <50 % of the prescribed daily pedometer recordings. The primary outcome was 1-year major adverse events (MAE), defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, target vessel revascularization, and major amputation of the target limb. RESULTS: The mean age was 74.4 years; 78 % were male. A total of 623 lesions were analyzed (58.7 % aortoiliac, 41.3 % femoropopliteal). At 1 year, a lower cumulative incidence of MAE was observed in the good recording group compared to that in the poor recording group [10/233 (4.3 %) vs. 35/267 (13.7 %) patients, respectively; p < 0.001]. Multivariate Cox regression analysis showed that patients in the good recording group had a lower hazard ratio for 1-year MAE (0.33; 95 % confidence interval, 0.16-0.68; p = 0.004) than that in the poor recording group. CONCLUSIONS: Good self-recording of pedometer measurements was associated with favorable prognosis in patients with PAD following EVT.

DOI： 10.1016/j.jjcc.2022.09.005

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Transthyretin cardiac amyloidosis (ATTR-CA) is characterized by high 99mTc-labeled bone tracer uptake in the heart. However, the mechanism of bone tracer uptake into the heart remains controversial. Since bone tracer uptake into metastatic bone tumors is thought to be associated with increased bone metabolism, we examined 99mTc-pyrophosphate (PYP) scintigraphy findings, endomyocardial biopsy (EMB) tissue findings, and the expression of bone metabolism-related genes in the EMB tissues in patients with ATTR-CA, amyloid light-chain cardiac amyloidosis (AL-CA), and noncardiac amyloidosis (non-CA) in this study. The uptake of 99mTc-PYP in the heart was significantly higher in the ATTR-CA patients than in the AL-CA and non-CA patients. A higher percentage of ATTR-CA EMB tissue showed von Kossa-positive microparticles: ATTR-CA, 62%; AL-CA, 33%; and non-CA, 0%. Calcified microparticles were identified using transmission electron microscopy. However, none of the osteogenic marker genes, osteoclastic marker genes, or phosphate/pyrophosphate-related genes were upregulated in the EMB samples from ATTR-CA patients compared to those from AL-CA and non-CA patients. These results suggest that active calcification-promoting mechanisms are not involved in the microcalcification observed in the heart in ATTR-CA. The mechanisms explaining bone tracer uptake in the heart, which is stronger than that in the ribs, require further investigation.

DOI： 10.3390/ijms24031921

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Atrial septal defect (ASD) closure can cause acute pulmonary edema. Before transcatheter closure is performed, temporary balloon occlusion test (BOT) is recommended in patients with left ventricular dysfunction to predict the risk of pulmonary edema. However, the accuracy of BOT has not been verified. This study aimed to compare hemodynamic differences between BOT and transcatheter closure. METHODS: A total of 42 patients with a single ASD over age 18 years who underwent BOT before transcatheter ASD closure between October 2010 and May 2020 were analyzed. Pulmonary capillary wedge pressure (PCWP) was measured using a Swan-Ganz catheter placed in the pulmonary artery at baseline, after 10 min of BOT, and after transcatheter closure. Amplatzer septal occluder was used for all transcatheter closures. RESULTS: Mean patient age was 64 ± 18 years (range, 18-78). Mean ASD diameter and pulmonary to systemic flow ratio were 18 ± 5 and 2.8 ± 1.0 mm, respectively. Mean PCWP at baseline, during BOT, and after transcatheter closure was 8.9 ± 2.9, 13.5 ± 4.2, and 9.5 ± 2.6 mmHg, respectively. The difference between BOT and after transcatheter closure values was significant (p < 0.001). During BOT, PCWP increased ≥18 mmHg in 7 patients, whereas after ASD closure, PCWP was <18 mmHg in all 7 and none developed acute pulmonary edema. CONCLUSION: Temporary balloon occlusion of an ASD and transcatheter ASD closure result in different hemodynamic change. BOT overestimates increase of PCWP after transcatheter ASD closure and requires careful interpretation. Well-designed, larger studies in higher-risk patients are warranted to verify the clinical implications of BOT in more detail.

DOI： 10.1002/ccd.30556

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Limited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH. METHODS: This retrospective study examined lung pathology images of 764 patients with CHD-PAH aged <20 years whose lung specimens were submitted to the Japanese Research Institute of Pulmonary Vasculature for pulmonary pathological review between 2001 and 2020. Clinical information was collected retrospectively by each attending physician. The primary endpoint was cardiovascular death. RESULTS: The 5-year, 10-year, 15-year, and 20-year cardiovascular death-free survival rates for all patients were 92.0%, 90.4%, 87.3%, and 86.1%, respectively. The group with an IPVD of ≥2.0 had significantly poorer survival than the group with an IPVD <2.0 (P = .037). The Cox proportional hazards model adjusted for the presence of congenital anomaly syndromes associated with pulmonary hypertension, and age at lung biopsy showed similar results (hazard ratio 4.46; 95% confidence interval: 1.45-13.73; P = .009). CONCLUSIONS: The IPVD scoring system is useful for predicting the long-term outcome of CHD-PAH. For patients with an IPVD of ≥2.0, treatment strategies, including choosing palliative procedures such as pulmonary artery banding to restrict pulmonary blood flow and postponement of intracardiac repair, should be more carefully considered.

DOI： 10.3389/fcvm.2023.1212882

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

Here, we present a case of fat embolism syndrome (FES) in which ultrasound sonography and computed tomography successfully visualized fat embolus in the femoral vein. A multimodality approach was particularly useful for early and specific diagnosis.

DOI： 10.1002/ccr3.6552

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.6552

担当区分：責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：Texas Heart Institute Journal  

Anomalous origin of the left coronary artery from the opposite sinus of Valsalva with an intramural aortic course (L-ACAOS-IM) can cause syncope, sometimes as a prodrome of lethal events, including sudden cardiac death, in young athletes. The detailed mechanism of syncope in patients with L-ACAOS-IM is still unclear. This case report describes a 17-year-old boy who presented to the hospital because of syncope following chest pain with increasing frequency during exercise, such as playing soccer and running. In a treadmill exercise test, a decrease in blood pressure was seen (from 99/56 mm Hg to 68/38 mm Hg); chest pain and faintness accompanied by ST-segment elevation in lead aVR and ST-segment depression at other leads on electrocardiography were noted. These findings and symptoms disappeared spontaneously within a few minutes while clinicians prepared for emergency medications. Coronary computed tomography angiography (CCTA) showed that the origin of the left coronary artery (LCA) was the opposite sinus of Valsalva, and the course of the LCA was through the aortic wall toward the left coronary sinus. He was diagnosed with L-ACAOS-IM. After surgical treatment by unroofing the intramural part of the LCA and reconstructing a neo-ostium, he no longer experienced syncope during exercise. This case suggests that low cardiac output caused by myocardial ischemia, not life-threatening arrythmia, is a main mechanism of syncope in patients with L-ACAOS-IM. Consideration should be given to performing CCTA before an exercise stress test for young patients with syncope and chest pain to avoid the risk of severe myocardial ischemia.

DOI： 10.14503/thij-21-7677

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

Several studies have reported that the cardio-ankle vascular index (CAVI), a non-invasive measurement of arterial stiffness, is associated with the incidence of cardiovascular events. We investigated whether adding CAVI to a risk score improves the prediction of cardiovascular events in the setting of primary prevention. This retrospective observational study included consecutive 554 outpatients with cardiovascular disease risk factors but without known cardiovascular disease (68 ± 9 years, 64% men). The CAVI was measured using the VaSera vascular screening system. Major adverse cardiovascular events (MACE) included cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, and coronary revascularization. During a median follow-up of 4.3 years, cardiovascular events occurred in 65 patients (11.7%). Multivariate Cox analysis showed that abnormal CAVI (&gt;9.0) was significantly associated with the incidence of MACE (hazard ratio 2.31, 95% confidence interval 1.27–4.18). The addition of CAVI to the Suita score, a conventional risk score for coronary heart disease in Japan, significantly improved the C statics from 0.642 to 0.713 (p = 0.04). In addition to a conventional risk score, CAVI improved the prediction of cardiovascular events in patients with cardiovascular disease risk factors but without known cardiovascular diseases.

DOI： 10.3390/jcdd9110368

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記述言語：日本語   出版者・発行元：(公財)日本心臓財団  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00679&link_issn=&doc_id=20221018180015&doc_link_id=%2Fah2sinzd%2F2022%2F005410%2F019%2F1164-1169%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fah2sinzd%2F2022%2F005410%2F019%2F1164-1169%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sodium-glucose cotransporter 2 inhibitors could reduce cardiovascular events in patients with heart failure irrespective of diabetes status. In this prespecified sub-analysis of randomised-controlled trial, we investigated the efficacy of luseogliflozin (2.5 mg daily), a sodium-glucose cotransporter 2 inhibitor, with that of voglibose (0.6 mg daily), an alpha-glucosidase inhibitor, on high-risk lipid profile and inflammatory markers in patients with type-2 diabetes and heart failure. Among the 157 patients studied, there were no significant differences in the mean malondialdehyde LDL or small-dense LDL cholesterol levels between the luseogliflozin and voglibose groups (percent change: 0.2% vs. - 0.6%, p = 0.93; - 1.7% vs. - 8.6%, p = 0.21) after 12 weeks in comparison to levels at the baseline. No significant difference was observed between the two groups in the adiponectin and high-sensitivity C-reactive protein levels after 12 weeks compared to the baseline levels (percent change, - 1.6% vs. - 4.0% and 22.5% vs. 10.0%; p = 0.52 and p = 0.55, respectively). In conclusion, in patients with type-2 diabetes and heart failure, compared to voglibose, luseogliflozin did not significantly improve the high-risk lipoprotein profile including malondialdehyde LDL and small-dense LDL cholesterol or the levels of inflammatory markers, including adiponectin and high-sensitivity C-reactive protein.Trial registration: Trial number: UMIN-CTR, UMIN000018395; Registered 23 July 2015; URL: https://www.umin.ac.jp/ctr/index.htm .

DOI： 10.1038/s41598-022-19371-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

Aims

Acute myocardial infarction (AMI) is associated with left ventricular remodelling (LVR), which leads to progressive heart failure. Platelets play a pivotal role in promoting systemic and cardiac inflammatory responses during the complex process of myocardial wound healing or repair following AMI. This study aimed to investigate the impact of platelet reactivity immediately after primary percutaneous coronary intervention (PCI) on LVR in AMI patients with ST‐segment (STEMI) and non‐ST‐segment elevation (NSTEMI).

Methods and results

This prospective, single‐centre, observational study included 182 patients with AMI who underwent primary PCI (107 patient with STEMI and 75 patients with NSTEMI). Patients were administered a loading dose of aspirin plus prasugrel before the procedure, and platelet reactivity was assessed using the VerifyNow P2Y12 assay immediately after PCI. Echocardiography was performed before discharge and during the chronic phase (8 ± 3 months after discharge). LVR was defined as a relative ≥20% increase in left ventricular end‐diastolic volume index (LVEDVI). LVR in chronic phase was found in 34 patients (18.7%) whose platelet reactivity was significantly higher than those without LVR (259.6 ± 61.5 and 213.1 ± 74.8 P2Y12 reaction units [PRU]; P = 0.001). The occurrence of LVR did not differ between patients with STEMI and patients with NSTEMI (21.5% and 14.7%; P = 0.33). The optimal cut‐off value of platelet reactivity for discriminating LVR was ≥245 PRU. LVEDVI significantly decreased at chronic phase in patients without high platelet reactivity (&lt;245 PRU) (from 49.2 ± 13.5 to 45.4 ± 15.8 mL/m²; P = 0.02), but not in patients with high platelet reactivity (≥d245 PRU) (P = 0.06). Multivariate logistic analysis showed that high platelet reactivity was an independent predictor of LVR after adjusting for LVEDVI before discharge (odds ratio, 4.13; 95% confidence interval, 1.85–9.79).

Conclusions

High platelet reactivity measured immediately after PCI was a predictor of LVR in patients with AMI during the chronic phase. The role of antiplatelet therapy on inflammation in the myocardium is a promising area for further research.

DOI： 10.1002/ehf2.14100

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ehf2.14100

担当区分：筆頭著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

The 86thAnnual Scientific Meeting of the Japanese Circulation Society was held in a web-based format on March 11-13, 2022. In accordance with the internationalization policy of the JCS, the meeting was held with the Asian Pacific Society of Cardiology Congress 2022. The main theme was "Cardiology Spreading its Wings". The number of patients with heart failure and other cardiovascular diseases is increasing dramatically, and the fields dealt with by cardiovascular medicine are also greatly expanding. This conference was both intellectually satisfying and exciting for all participants, who numbered over 14,900. The meeting was completed with great success, and the enormous amount of cooperation and support from all involved was greatly appreciated.

DOI： 10.1253/circj.CJ-22-0349

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

Aims

Some reports have suggested that hypertensive acute heart failure (AHF) is caused by intravascular congestion, not interstitial congestion. We evaluated the differences in extracellular fluid volume assessed by bioelectrical impedance analysis (BIA) between AHF patients with and without high systolic blood pressure (sBP).

Methods

This prospective single‐centre study (UMIN000030266) included 178 patients hospitalized due to AHF between September 2017 and August 2018. We calculated extracellular water (ECW), intracellular water (ICW), total body water (TBW), and ECW‐to‐TBW ratio (oedema index: EI) by BIA and evaluated conventional parameters as follows: weight, N‐terminal pro brain natriuretic peptide values, and echocardiography parameters on admission and before discharge. One‐year outcomes included all‐cause death and re‐admission due to heart failure. We compared patients with sBP &gt; 140 mmHg on admission [clinical scenario 1 (CS1) group] and with sBP of ≤140 mmHg on admission (non‐CS1 group).

Results

The mean age of the patients was 79.5 ± 11.1 years, and 48.9% of the patients were female. EI on admission of 83 patients in the CS1 group was lower than that of 95 patients in the non‐CS1 group. The change in EI from admission to before discharge was no significant in the CS1 group but was significant in the non‐CS1 group. Comparing the changes from admission to before discharge between the CS1 and the non‐CS1 group, delta ECW, delta ICW, delta TBW, and delta EI of the CS1 group were significantly smaller than those of the non‐CS1 group. During the 1‐year follow‐up period after discharge of the 178 patients, the numbers of deaths and re‐admissions due to acute HF were 26 (15%) and 49 (28%), respectively. Patients with high EI before discharge [&gt;0.408 (median)] had significantly more cardiac events than patients with low EI [hazard ratio (HR): 2.15, 95% confidence interval (CI): 1.30–3.55]. Cox regression analysis revealed that higher EI as a continuous variable was significantly associated with worse outcome in non‐CS1 group (HR: 1.46, 95% CI: 1.13–1.87), but not significantly associated with worse outcome in CS1 group (HR: 1.29, 95% CI: 0.98–1.69).

Conclusions

EI on admission in patients with high sBP was not elevated, and changes in ECW, ICW, TBW, and EI in patients with high sBP were smaller than those in patients without high sBP. EI measured by BIA could distinguish AHF with interstitial or intravascular congestion.

DOI： 10.1002/ehf2.14067

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ehf2.14067

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Circulation Society  

DOI： 10.1253/circj.cj-21-0529

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This study aimed to elucidate the utility of a novel ultrasound-based technique, shear wave dispersion slope (SWDS) analysis, which estimates tissue viscosity, for evaluating the severity of myocardial inflammation. Experimental autoimmune myocarditis (EAM) at different disease phases [3-week (acute phase): n = 10, 5-week (subacute phase): n = 9, and 7-week (late phase): n = 11] were developed in male Lewis rats. SWDS was measured in the right and the left ventricular free walls (RVFW and LVFW) under a retrograde perfusion condition. Histological myocardial inflammation was evaluated by CD68 staining. The accumulation of CD68-positive cells was severe in the myocardium of the EAM 3-week group. The median (interquartile range) SWDS of RVFW was significantly higher in the EAM 3-week group [9.9 (6.5-11.0) m/s/kHz] than in the control group [5.4 (4.5-6.8) m/s/kHz] (P = 0.034). The median SWDS of LVFW was also significantly higher in the EAM 3-week group [8.1 (6.4-11.0) m/s/kHz] than in the control group [4.4 (4.2-4.8) m/s/kHz] (P = 0.003). SWDS and the percentage of CD68-positive area showed a significant correlation in RVFW (R2 = 0.64, P < 0.001) and LVFW (R2 = 0.73, P < 0.001). This study showed that SWDS was elevated in ventricular walls with acute inflammation and also significantly correlated with the degree of myocardial inflammation. These results suggest the potential of SWDS in estimating the histological severity of acute myocarditis.

DOI： 10.1038/s41598-022-12935-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s00380-022-02084-1

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その他リンク： https://link.springer.com/article/10.1007/s00380-022-02084-1/fulltext.html

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Dual-energy computed tomography (DECT) is a promising technique for the assessment of the lung perfused blood volume (LPBV) in the lung parenchyma. This study was performed to compare the LPBV by DECT of patients with pulmonary hypertension (PH) and controls and to evaluate the association between the LPBV and the perfusion ratio derived by lung perfusion scintigraphy. This study involved 45 patients who underwent DECT (25 patients with PH and 20 controls). We measured the total LPBV and distribution of the LPBV in each lung. The total LPBV was significantly lower in the PH group than the control group (38 ± 9 vs. 45 ± 8 HU, p = 0.024). Significant differences were observed between the LPBV of the upper lung of the PH and control groups (34 ± 10 vs. 47 ± 10, p = 0.021 and 37 ± 10 vs. 47 ± 8, p &lt; 0.001). A significant correlation was observed between the LPBV and the lung perfusion scintigraphy. A lower total LPBV and lower LPBV of the upper lung as detected by DECT might be specific findings of PH.

DOI： 10.3390/life12050684

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The number of patients with bradyarrhythmia and the number of patients with cardiac pacemakers are increasing with the aging population and the increase in the number of patients with heart diseases. Some patients in whom a cardiac pacemaker has been implanted experience problems such as pacemaker infection and inconvenience due to electromagnetic interference. We have reported that overexpression of HCN channels producing a pacemaker current in mouse embryonic stem cell-derived cardiomyocytes showed enhanced pacing function in vitro and in vivo. The aim of this study was to determine whether HCN4 overexpression in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can strengthen the pacing function of the cells. METHODS: Human HCN4 was transduced in the AAVS1 locus of human induced pluripotent stem cells by nucleofection and HCN4-overexpressing iPSC-CMs were generated. Gene expression profiles, frequencies of spontaneous contraction and pacing abilities of HCN4-overexpressing and non-overexpressing iPSC-CMs in vitro were compared. RESULTS: HCN4-overexpressing iPSC-CMs showed higher spontaneous contraction rates than those of non-overexpressing iPSC-CMs. They responded to an HCN channel blocker and β adrenergic stimulation. The pacing rates against parent iPSC line-derived cardiomyocytes were also higher in HCN4-overexpressing iPSC-CMs than in non-overexpressing iPSC-CMs. CONCLUSIONS: Overexpression of HCN4 showed enhancement of If current, spontaneous firing and pacing function in iPSC-CMs. These data suggest this transgenic cell line may be useful as a cardiac pacemaker.

DOI： 10.1186/s13287-022-02818-y

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担当区分：筆頭著者,　責任著者   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

There is a close relationship between diabetes mellitus and heart failure, and diabetes is an independent risk factor for heart failure. Diabetes and heart failure are linked by not only the complication of ischemic heart disease, but also by metabolic disorders such as glucose toxicity and lipotoxicity based on insulin resistance. Cardiac dysfunction in the absence of coronary artery disease, hypertension, and valvular disease is called diabetic cardiomyopathy. Diabetes-induced hyperglycemia and hyperinsulinemia lead to capillary damage, myocardial fibrosis, and myocardial hypertrophy with mitochondrial dysfunction. Lipotoxicity with extensive fat deposits or lipid droplets is observed on cardiomyocytes. Furthermore, increased oxidative stress and inflammation cause cardiac fibrosis and hypertrophy. Treatment with a sodium glucose cotransporter 2 (SGLT2) inhibitor is currently one of the most effective treatments for heart failure associated with diabetes. However, an effective treatment for lipotoxicity of the myocardium has not yet been established, and the establishment of an effective treatment is needed in the future. This review provides an overview of heart failure in diabetic patients for the clinical practice of clinicians.

DOI： 10.3390/ijms23073587

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Doxorubicin (DOX)-based chemotherapy induces cardiotoxicity, which is considered the main bottleneck for its clinical application. In this study, we investigated the potential benefit of LCZ696, an angiotensin receptor-neprilysin inhibitor against DOX-induced cardiotoxicity in rats and H9c2 cells and determined whether the mechanism underlying any such effects involves its antioxidant activity. Male Sprague-Dawley rats were randomly separated into four groups, each consisting of 15 rats (DOX (1.5 mg/kg/day intraperitoneally for 10 days followed by non-treatment for 8 days); DOX + valsartan (31 mg/kg/day by gavage from day 1 to day 18); DOX + LCZ696 (68 mg/kg/day by gavage from day 1 to day 18); and control (saline intraperitoneally for 10 days). DOX-induced elevation of cardiac troponin T levels on day 18 was significantly reduced by LCZ696, but not valsartan. The DOX-induced increase in myocardial reactive oxygen species (ROS) levels determined using dihydroethidium was significantly ameliorated by LCZ696, but not valsartan, and was accompanied by the suppression of DOX-induced increase in p47phox. LCZ696 recovered the DOX-induced decrease in phosphorylation of adenosine monophosphate-activated protein kinase and increased the ratio of Bax and Bcl-2. In H9c2 cardiomyocytes, LCZ696 reduced DOX-induced mitochondrial ROS generation and improved cell viability more than valsartan. Our findings indicated that LCZ696 ameliorated DOX-induced cardiotoxicity in rat hearts in vivo and in vitro, possibly by mediating a decrease in oxidative stress.

DOI： 10.1038/s41598-022-09094-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Decreases in circulating CD34-positive cells are associated with increases in cardiovascular events. We investigated the association between the number of CD34-positive cells and the progression of coronary artery calcification (CAC), a marker of atherosclerosis, in patients with hypercholesteremia under statin therapy in a sub-analysis of a multicenter study. METHODS: In the principal study, patients with CAC scores of 1-999 were treated with pitavastatin. Measurement of CAC by non-enhanced computed tomography and a blood test were performed at baseline and at 1-year follow-up. Patients were divided into two groups: CAC progression (change in CAC score > 0) and non-progression. The number of circulating CD34-positive cells was counted using flow cytometry. RESULTS: A total of 156 patients (mean age 67 years, 55% men) were included in this sub-analysis. CD34 positive cell numbers at baseline as a continuous variable was inversely correlated with annual change in the log-transformed CAC score (r = -0.19, p = 0.02). When patients were divided into high and low CD34 groups based on the median value of 0.8 cells/μL, the adjusted change in CAC score in the low-CD34 group was significantly greater than that in the high-CD34 group (54.2% vs. 20.8%, respectively, p = 0.04). In multiple logistic analysis, a low CD34-positive cell number was an independent predictor of CAC progression, with an odds ratio of 2.88 (95% confidence interval 1.28-6.49, p = 0.01). CONCLUSIONS: Low numbers of CD34-positive cells are associated with CAC progression in patients with hypercholesterolemia under statin therapy. The number of CD34-positive cells may help to identify patients at increased cardiovascular risk.

DOI： 10.5603/CJ.a2021.0151

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Multiple spikes within the QRS complex, known as fragmented QRS (fQRS), are associated with the occurrences of ventricular arrhythmic events (VAEs) in patients with Brugada syndrome and hypertrophic cardiomyopathy. However, the association between fQRS and occurrence of VAEs in patients with cardiac sarcoidosis (CS) has not been elucidated. METHODS: We evaluated the associations between fQRS and cardiac events including VAEs [non-sustained ventricular tachycardia (NSVT), sustained ventricular tachycardia (VT), and ventricular fibrillation (VF)], hospitalization for heart failure, and all-cause death in 68 patients with CS (30 patients with fQRS vs. 38 patients without fQRS) over a 5-year period. RESULTS: Cardiac events occurred in 22 patients with fQRS and 18 patients without fQRS (73% vs. 47%, p=0.009). Of the cardiac events that occurred in CS patients, VAEs occurred more frequently in patients with fQRS than in patients without fQRS (VAEs: 70% vs. 45%, p=0.017; NSVT: 70% vs. 45%, p=0.010; VT: 43% vs. 18%, p=0.011, and VF: 6.7% vs. 2.6%, p=0.34), whereas there was no significant difference in hospitalization for heart failure or all-cause death between patients with and those without fQRS (hospitalization for heart failure: 6.7% vs. 5.3%, p=0.75; all-cause death: 6.7% vs. 5.3%, p=0.64). Multivariate analysis showed that fQRS in the baseline electrocardiogram was independently associated with VAEs (hazard ratio: 2.21, 95% confidence interval: 1.15-4.25, p=0.017). CONCLUSION: fQRS is a predictor of VAEs in patients with CS.

DOI： 10.1016/j.jjcc.2021.10.022

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Sodium glucose co-transporter 2 inhibitors have diuretic effects in both patients with glycosuria and with natriuresis. We sought to assess the effect of luseogliflozin on estimated plasma volume (ePV) in patients with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: This study was a post-hoc analysis of the MUSCAT-HF trial (UMIN000018395), a multicentre, prospective, open-label, randomized controlled trial that assessed the effect of 12 weeks of luseogliflozin (2.5 mg, once daily, n = 83) as compared with voglibose (0.2 mg, three times daily, n = 82) on the reduction in brain natriuretic peptide (BNP) in patients with type 2 diabetes and HFpEF. The analysis compared the change in ePV calculated by the Straus formula from baseline to Weeks 4, 12, and 24, using a mixed-effects model for repeated measures. We also estimated the association between changes in ePV and changes in other clinical parameters, including BNP levels. Luseogliflozin significantly reduced ePV as compared to voglibose at Week 4 {adjusted mean group-difference -6.43% [95% confidence interval (CI): -9.11 to -3.74]}, at Week 12 [-8.73% (95%CI: -11.40 to -6.05)], and at Week 24 [-11.02% (95%CI: -13.71 to -8.33)]. The effect of luseogliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in ePV at Week 12 was significantly associated with log-transformed BNP (r = 0.197, P = 0.015) and left atrial volume index (r = 0.283, P = 0.019). CONCLUSIONS: Luseogliflozin significantly reduced ePV in patients with type 2 diabetes and HFpEF, as compared with voglibose. The reduction of intravascular volume by luseogliflozin may provide clinical benefits to patients with type 2 diabetes and HFpEF.

DOI： 10.1002/ehf2.13683

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: This study aimed to investigate additional risk stratification benefits of hepatic steatosis (HS) concurrently assessed during coronary computed tomography angiography (CTA) in a large patient cohort with suspected stable coronary artery disease (CAD). METHODS AND RESULTS: In this prospective study, 1148 Japanese outpatients without a history of CAD who underwent coronary CTA for suspected stable CAD (mean age 64 ± 14 years) were included. HS, defined on CT as a hepatic-to-spleen attenuation ratio of <1.0, was examined just before the evaluation of adverse CTA findings, defined as obstructive and/or high-risk plaque. The major adverse cardiac events (MACE) were the composite of cardiac death, acute coronary syndrome, and late revascularization. The incremental predictive value of HS was evaluated using the global χ2 test and C-statistic. HS was identified in 247 (22%) patients. During a median follow-up of 3.9 years, MACE was observed in 40 (3.5%) patients. HS was significantly associated with MACE in a model that included adverse CTA findings (hazard ratio 4.01, 95% confidence interval 2.12-7.59, P < 0.001). By adding HS to the Framingham risk score and adverse CTA findings, the global χ2 score and C-statistic significantly increased from 29.0 to 49.5 (P < 0.001) and 0.74 to 0.81 (P = 0.026), respectively. In subgroup analyses in patients with diabetes mellitus and metabolic syndrome, HS had significant additive predictive value for MACE over the Framingham risk score and adverse CTA findings. CONCLUSION: In patients with suspected stable CAD, concurrent evaluation of HS during coronary CTA enables more accurate detection of patients at higher risk of MACE.

DOI： 10.1093/eurjpc/zwab120

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

Aims

The relief of congestion is essential for the prevention of worsening heart failure (HF) resulting in hospitalizations. Assessment of the degree of organ congestion in the chronic phase of HF is important for determining therapeutic strategies. The aim of this study was to evaluate the efficacy of shear wave (SW) elasticity for assessing congestion and clinical outcomes in patients with chronic HF.

Methods and results

We prospectively enrolled 345 consecutive patients with chronic HF who underwent SW elastography at outpatient clinic. Patients were divided into two groups according to the median value of SW elasticity: low group (SW elasticity &lt;6.4 kPa, n = 176) and high group (SW elasticity ≥6.4 kPa, n = 169). The endpoint was cardiovascular death or hospitalization for HF. During the median follow‐up period of 19 months (range: 7–36 months), cardiovascular death or hospitalization for HF occurred in 4 patients of low group and 27 patients of high group. In high group, 8 patients died, and 19 patients were hospitalized for HF. In low group, 3 patients died, and 1 patient was hospitalized. Kaplan–Meier analysis showed that the event‐free survival rate was worse in high group than in low group (log‐rank test, P = 0.004). After adjusting for variables, high SW elasticity was independently related to cardiac events. In multivariate regression analysis, SW elasticity was correlated with left atrial volume index, early diastolic mitral inflow velocity to mitral annular velocity ratio, and inferior vena cava diameter.

Conclusions

The SW elasticity reflected haemodynamic congestion in patients with chronic HF, which was related to cardiac events.

DOI： 10.1002/ehf2.13809

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ehf2.13809

担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.18926/AMO/63219

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Abdominal aortic aneurysm (AAA) is a life-threatening disease that lacks effective preventive therapies. This study aimed to evaluate the effect of pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPARα) agonist, on AAA formation and rupture. Methods: Experimental AAA was induced by subcutaneous angiotensin II (AngII) infusion in ApoE - / - mice for 4 weeks. Pemafibrate (0.1 mg/kg/day) was administered orally. Dihydroethidium staining was used to evaluate the reactive oxygen species (ROS). Results: The size of the AngII-induced AAA did not differ between pemafibrate- and vehicle-treated groups. However, a decreased mortality rate due to AAA rupture was observed in pemafibrate-treated mice. Pemafibrate ameliorated AngII-induced ROS and reduced the mRNA expression of interleukin-6 and tumor necrosis factor-α in the aortic wall. Gelatin zymography analysis demonstrated significant inhibition of matrix metalloproteinase-2 activity by pemafibrate. AngII-induced ROS production in human vascular smooth muscle cells was inhibited by pre-treatment with pemafibrate and was accompanied by an increase in catalase activity. Small interfering RNA-mediated knockdown of catalase or PPARα significantly attenuated the anti-oxidative effect of pemafibrate. Conclusion: Pemafibrate prevented AAA rupture in a murine model, concomitant with reduced ROS, inflammation, and extracellular matrix degradation in the aortic wall. The protective effect against AAA rupture was partly mediated by the anti-oxidative effect of catalase induced by pemafibrate in the smooth muscle cells.

DOI： 10.3389/fcvm.2022.904215

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jjcc.2022.03.014

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1161/CIRCULATIONAHA.121.058869

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cardiac involvement has a profound effect on the prognosis of patients with systemic amyloidosis. Therapeutic methods for suppressing the production of causative proteins have been developed for ATTR amyloidosis and AL amyloidosis, which show cardiac involvement, and the prognosis has been improved. However, a method for removing deposited amyloid has not been established. Methods for reducing cytotoxicity caused by amyloid deposition and amyloid precursor protein to protect cardiovascular cells are also needed. In this review, we outline the molecular mechanisms and treatments of cardiac amyloidosis.

DOI： 10.3390/ijms23010025

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Shear wave (SW) imaging is a novel ultrasound-based technique for assessing tissue characteristics. SW elasticity may be useful to assess the severity of hypertensive left ventricular (LV) hypertrophy. This study aimed to evaluate the efficacy of SW elasticity for assessing the degree of myocardial hypertrophy using hypertensive rats. Rats were divided into hypertension group and control group. SW elasticity was measured on the excised heart. Myocardial hypertrophy was assessed histologically. LV weight was greater in hypertension group. An increase in interventricular septum and LV free wall thicknesses was observed in hypertension group. SW elasticity was significantly higher in hypertension group than in control group (14.6 ± 4.3 kPa vs. 6.5 ± 1.1 kPa, P < 0.01). The cross-sectional area of cardiomyocytes was larger in hypertension group than in control group (397 ± 50 μm2 vs. 243 ± 14 μm2, P < 0.01), and SW elasticity was positively correlated with the cross-sectional area of cardiomyocytes (R = 0.96, P < 0.01). This study showed that SW elasticity was higher in hypertensive rats and was closely correlated with the degree of myocardial hypertrophy, suggesting the efficacy of SW elasticity for estimating the severity of hypertensive LV hypertrophy.

DOI： 10.1038/s41598-021-02271-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Perioperative atrial fibrillation (POAF) after non-cardiac surgery is a risk factor for cardiovascular events including stroke and death. The aim of this subanalysis of the MAMACARI study, a multicenter randomized control study on the effectiveness of a bisoprolol transdermal patch for prevention of perioperative myocardial injury in high-risk patients undergoing non-cardiac surgery, was to identify the predictors of POAF after non-cardiac surgery in high-risk patients and to determine changes in blood pressure and heart rate during bisoprolol patch administration in the perioperative period. METHODS AND RESULTS: Patients aged over 60 years with hypertension and a high revised cardiac risk index (≥2) who were scheduled to undergo non-cardiac surgery were randomly assigned to a bisoprolol patch group (n = 120) or a control group (n = 120). We divided the patients into two groups: patients with POAF (POAF group; n = 16) and patients without POAF (non-POAF group; n = 206). Multivariate analysis showed that bisoprolol patch therapy (OR: 0.30, 95% CI: 0.092-0.978) and surgery time of 250 min or more (OR: 4.99, 95% CI: 1.37-18.2) were independently associated with POAF. Although systolic blood pressure did not differ significantly between the two groups throughout the perioperative period, treatment with a bisoprolol patch significantly reduced heart rate throughout the perioperative period compared with that in the control group. CONCLUSIONS: Low dose of a bisoprolol patch in the perioperative period was effective for prevention of POAF after non-cardiac surgery in high-risk patients, while long surgery time was an independent risk factor for POAF. It is expected that low dose of a bisoprolol patch can prevent POAF without causing hypotension.

DOI： 10.1016/j.jjcc.2021.05.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Numerous basic studies have shown a relationship between interleukin-6 (IL-6) and the development or severity of myocarditis. However, there has been no study in which the effect of IL-6 levels in patients with myocarditis was evaluated. METHODS: We enrolled control patients (n = 12) and consecutive patients with acute myocarditis (n = 13), including lymphocytic, eosinophilic, and giant cell myocarditis, and investigated the pathological and clinical effects of IL-6 on human myocarditis. RESULTS: The serum IL-6 level in patients with myocarditis (16.7 [9.9, 103.8] pg/mL) was significantly higher than that in the control patients (1.4 [1.0, 1.9] pg/mL) (P<0.001). Immunohistochemical analysis showed that IL-6 was expressed in infiltrating inflammatory cells of endomyocardial biopsy samples from all patients with myocarditis. Moreover, the log-transformed value of serum IL-6 level showed significant positive correlations with serum creatine kinase (CK) level, CK-MB level, peak CK level, peak CK-MB level and C-reactive protein level (all P ≤ 0.005) and a negative correlation with the left ventricular (LV) ejection fraction (p = 0.014). We divided the patients with myocarditis into a low IL-6 group (9.9 [4.5, 14.2] pg/dL, n = 7) and a high IL-6 group (108.9 [51.1, 130.9] pg/dL, n = 6). The degree of infiltration of IL-6-expressing inflammatory cells in myocardial samples obtained from patients in the high IL-6 group was significantly more severe than that in samples obtained from patients in the low IL-6 group. Furthermore, patients in the high IL-6 group significantly more frequently received catecholamine therapy (P = 0.005), venoarterial extracorporeal membrane oxygenation (P = 0.029), and artificial respirator support (P = 0.021) in the acute phase of myocarditis. CONCLUSION: The results suggest that there is a strong impact of IL-6 on cardiac injury and dysfunction in patients with myocarditis.

DOI： 10.1016/j.jjcc.2021.03.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Right ventricular (RV) function is important for outcomes in pulmonary hypertension. Evaluation of RV myocardial characteristics is useful to assess the disease severity. Shear wave elastography (SWE) provides information of shear wave (SW) elasticity, which is related to tissue hardness, and SW dispersion slope, which reflects tissue viscosity. This study aimed to test the hypothesis that SW elasticity is increased and SW dispersion slope is decreased in the right ventricle of monocrotaline (MCT)-induced pulmonary hypertension rats. METHODS: Rats were divided into MCT-induced pulmonary hypertension group (n = 10) and control group (n = 10). SW elasticity and SW dispersion slope were measured on excised hearts. Myocardial fibrosis was evaluated histologically. RESULTS: RV hypertrophy was observed in the MCT group. SW elasticity of right ventricle was higher in the MCT group than in the control group (3.5 ± 0.9 kPa vs. 2.5 ± 0.4 kPa, p < 0.01). SW dispersion slope of right ventricle was lower in the MCT group than in the control group (5.3 ± 1.7 m/s/kHz vs. 7.7 ± 1.5 m/s/kHz, p < 0.01). The fibrosis area of right ventricle was increased in MCT group compared with control group (18 ± 5% vs. 8 ± 3%, p < 0.01), and was positively related to SW elasticity and negatively related to SW dispersion slope. CONCLUSIONS: Higher SW elasticity and lower SW dispersion slope were observed in the fibrotic myocardium of right ventricle in MCT-induced pulmonary hypertension rats. SWE may have the potential to evaluate RV function by assessing myocardial characteristics.

DOI： 10.1016/j.jjcc.2021.01.015

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.cardfail.2021.04.010

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The receptor for advanced glycation end products (RAGE), a transmembrane receptor belonging to the immunoglobulin superfamily, is overexpressed in pulmonary artery smooth muscle cells (PASMCs) in patients with pulmonary arterial hypertension (PAH) and is implicated in the etiology of PAH. Recently, we reported that RAGE-aptamer, a short and single-stranded DNA directed against RAGE, inhibited an inappropriate increase in cultured PASMCs in PAH. The aim of this study was to determine the efficacy of RAGE-aptamer in monocrotaline-induced PAH in rats. METHODS AND RESULTS: Rats were assigned to either an untreated control group, a group that received continuous subcutaneous administration of RAGE-aptamer immediately after monocrotaline injection, or a group that received control-aptamer immediately after monocrotaline injection. All rats survived 21 days after injection of monocrotaline and control-aptamer or RAGE-aptamer. Injection of monocrotaline with continuous subcutaneous delivery of control-aptamer resulted in higher right ventricular systolic pressure compared with controls. This increase was attenuated by continuous subcutaneous delivery of RAGE-aptamer. The proportion of small pulmonary arteries with full muscularization was greater in the monocrotaline and control-aptamer group than in the control group. Continuous subcutaneous delivery of RAGE-aptamer significantly reduced the percentage of small pulmonary arteries with full muscularization. CONCLUSIONS: Continuous subcutaneous delivery of RAGE-aptamer suppresses development of monocrotaline-induced PAH in rats. Inhibition of RAGE ameliorates muscularization of small pulmonary arteries. Treatment with RAGE-aptamer might be a new therapeutic option for PAH.

DOI： 10.1016/j.jjcc.2020.12.009

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Early treatment with an oral β-blocker is recommended in patients with a ST-segment-elevation myocardial infarction (STEMI). In this multicenter study, we evaluated the effects of a continuous administration of landiolol, an ultrashort-acting β-blocker, before primary percutaneous coronary intervention (PCI) on myocardial salvage and its safety in STEMI patients. A total of 47 Japanese patients with anterior or lateral STEMI undergoing a primary PCI within 12 h of symptom onset were randomized to receive intravenous landiolol (started at 3 μg/min/kg dose and continued to a total of 50 mg; n=23) or not (control; n=24). Patients with Killip class III or more were excluded. The primary outcome was the myocardial salvage index on cardiac magnetic resonance imaging (MRI) performed 5-7 days after the PCI. Cardiac MRI was performed in 35 patients (74%). The myocardial salvage index in the landiolol group was significantly greater than that in the control group (44.4±14.6% vs. 31.7±18.9%, respectively; p=0.04). There were no significant differences in adverse events at 24 h between the landiolol and control groups. A continuous administration of landiolol before a primary PCI may increase the degree of myocardial salvage without additional hemodynamic adverse effects within the first 24 h after STEMI.

DOI： 10.18926/AMO/62220

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Oxidized high-density lipoprotein (oxHDL), unlike native HDL, is characterized by reduced cholesterol efflux capability and anti-inflammatory properties. The ratio of oxHDL to apolipoprotein A-I (oxHDL/apoAI) is a possible marker of dysfunctional HDL. The aim of this study was to evaluate the association between oxHDL/apoAI and coronary plaque characteristics that increase the likelihood of cardiovascular events as determined by coronary computed tomography (CT) angiography. METHODS: A total of 297 patients (mean age; 67 years, men; 63%) who underwent coronary CT angiography for suspected stable coronary artery disease (CAD) were included. High-risk plaques (HRP) were defined by three characteristics: positive remodeling; low-density plaques; and spotty calcification. Significant stenosis was defined as a luminal narrowing of >70%. Serum concentrations of oxHDL were measured using an enzyme-linked immunosorbent assay. RESULTS: Patients with higher oxHDL/ApoAI showed significantly greater prevalence of HRP (p = 0.03) and significant stenosis (p < 0.01) compared with patients with low oxHDL/ ApoAI. The multivariate logistic analysis demonstrated that oxHDL/ApoAI significantly associated with the presence of HRP and significant coronary stenosis (p = 0.01 and < 0.01). In the follow-up study including 243 patients for a median period of 1.8 years, univariate cox regression analysis showed that oxHDL/ApoAI, HRP and significant stenosis were significant predictors of cardiovascular events. CONCLUSIONS: A high oxHDL/apoAI was associated with the presence of HRP and significant stenosis determined by coronary CT angiography, which can lead to cardiovascular events in patients with suspected stable CAD.

DOI： 10.1016/j.ijcard.2020.09.060

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Remote ischemic preconditioning (RIPC) is a promising strategy for protecting against ischemic reperfusion injury. This study is a secondary analysis of a randomized study that aimed to evaluate the effect of RIPC on the early increase in serum creatinine (SCr) following percutaneous coronary intervention (PCI), which is associ-ated with contrast-induced acute kidney injury. Patients with stable angina undergoing elective PCI were assigned to control, RIPC, and continuous infusion of nicorandil (nicorandil) groups. The endpoint of this study was the incidence of the early increase in SCr, a predictor of contrast-induced acute kidney injury, which was defined as either a > 20% or absolute increase by 0.3 mg/dl of SCr levels after 24 h of PCI. This study included 220 patients for whom a dataset of SCr values was available. The incidence of the early increase in SCr was significantly lower in the RIPC than in the control (1.3% vs 10.8%, p = 0.03) group, but was not significantly different between the nicorandil and control groups. In multivariate analysis, RIPC remained a significant fac-tor associated with a reduction in the incidence of early increase in SCr. RIPC reduces the incidence of early increase in SCr in patients with stable angina following elective PCI.

DOI： 10.18926/AMO/61433

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Transvenous lead extraction (TLE) is necessary because of system infection, lead malfunction, or system upgrade. Patients with severe left ventricular dysfunction (SLVD) undergoing TLE may be at a higher risk because hemodynamic parameters may change unfavorably during or after TLE; however, this has not yet been clarified. OBJECTIVE: The purpose of this study was to examine whether patients with SLVD undergoing TLE have higher mortality. METHODS: All patients who underwent TLE were stratified as follows: patients with ejection fraction ≤ 35% (SLVD group) and those with ejection fraction > 35% (non-SLVD group). RESULTS: We assessed the data of 200 patients (SLVD group, 36; non-SLVD group, 164). Brain natriuretic peptide level and cardiac resynchronization therapy rate were higher in the SLVD group than in the non-SLVD group. There were no significant between-group differences in major complications and clinical success rates. Patients with SLVD were more likely to require additional hemodynamic support, such as catecholamine infusion, temporary atrial-ventricle sequential pacing, and temporary cardiac resynchronization therapy pacing (27.8% vs 1.2%; P < .001). The survival rate was not significantly different between the groups at 30 days and 1 year after TLE (SLVD vs non-SLVD: 30 days: 97.2% vs 99.4%; P = .215; 1 year: 80.6% vs 91.5%; P = .053). Multivariate Cox regression analysis revealed log brain natriuretic peptide and serum hemoglobin levels as predictors for 1-year mortality. CONCLUSION: The prognosis after TLE was comparable between patients with and without SLVD. However, additional hemodynamic support was often necessary for patients with SLVD.

DOI： 10.1016/j.hrthm.2021.01.026

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The latest guideline from the European Society of Cardiology and European Respiratory Society recommends initial combination therapy with oral pulmonary arterial hypertension (PAH)-specific drugs in PAH patients with World Health Organization functional class (WHO-FC) II or III. However, whether this initial combination therapy improves hemodynamics and clinical failure events regardless of the combination of PAH-specific drugs remains unknown. This study was designed to evaluate whether the initial combination therapy with macitentan plus riociguat or macitentan plus selexipag showed equal efficacy in reducing pulmonary vascular resistance (PVR) 8 months after administration. Methods and Results: This study is a multicenter randomized control trial. PAH subjects with WHO-FC II or III will be randomized (1 : 1) into initial combination therapy with either macitentan plus riociguat or macitentan plus selexipag, and will be observed 8 months after the initiation of treatment. The primary endpoint will be the difference in the change ratio of PVR from baseline to after 8 months of treatment. Conclusions: The SETOUCHI-PH study will clarify whether initial combination therapy with macitentan plus riociguat or macitentan plus selexipag results in equal reductions in PVR 8 months after administration.

DOI： 10.1253/circrep.CR-20-0133

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Risk stratification of cardiovascular events in patients with type 2 diabetes mellitus (T2DM) has not been established. Coronary artery calcium score (CACS) and non-alcoholic fatty liver disease (NAFLD) are independently associated with cardiovascular events in T2DM patients. This study examined the incremental prognostic value of NAFLD assessed by non-enhanced computed tomography (CT) in addition to CACS and Framingham risk score (FRS) for cardiovascular events in T2DM patients. METHODS: This prospective pilot study included 529 T2DM outpatients with no history of cardiovascular disease who underwent CACS measurement because of suspected coronary artery disease. NAFLD was defined on CT images as a liver:spleen attenuation ratio < 1.0. Cardiovascular events were defined as cardiovascular death, nonfatal myocardial infarction, late coronary revascularization, nonfatal stroke, or hospitalization for heart failure. RESULTS: Among 529 patients (61% men, mean age 65 years), NAFLD was identified in 143 (27%). Forty-four cardiovascular events were documented during a median follow-up of 4.4 years. In multivariate Cox regression analysis, NAFLD, CACS, and FRS were associated with cardiovascular events (hazard ratios and 95% confidence intervals 5.43, 2.82-10.44, p < 0.001; 1.56, 1.32-1.86, p < 0.001; 1.23, 1.08-1.39, p = 0.001, respectively). The global χ2 score for predicting cardiovascular events increased significantly from 27.0 to 49.7 by adding NAFLD to CACS and FRS (p < 0.001). The addition of NAFLD to a model including CACS and FRS significantly increased the C-statistic from 0.71 to 0.80 (p = 0.005). The net reclassification achieved by adding CACS and FRS was 0.551 (p < 0.001). CONCLUSIONS: NAFLD assessed by CT, in addition to CACS and FRS, could be useful for identifying T2DM patients at higher risk of cardiovascular events.

DOI： 10.1186/s12933-020-01192-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: High-risk patients can be identified by preprocedural computed tomography (CT) before lead extraction. However, CT evaluation may be difficult especially for lead tip identification due to artifacts in the leads. Selective right ventriculography (RVG) may enable preprocedural evaluation of lead perforation. We investigated the efficacy of RVG for identifying right ventricular (RV) lead perforation compared with CT in patients who underwent lead extraction. METHODS: Ninety-five consecutive patients who were examined by thin-section non-ECG-gated multidetector CT and RVG before lead extraction were investigated retrospectively. Newly recognized pericardial effusion after lead extraction was used as a reference standard for lead perforation. We analyzed the prevalence of RV lead perforation diagnosed by each method. The difference in the detection rates of lead perforation by RVG and CT was evaluated. RESULTS: Of the 115 RV leads in the 95 patients, lead perforation was diagnosed for 35 leads using CT, but the leads for 29 (83%) of those 35 leads diagnosed as lead perforation by CT were shown to be within the right ventricle by RVG. Three patients with 5 leads could not be evaluated by CT due to motion artifacts. The diagnostic accuracies of RVG and CT were significantly different (p < 0.001). There was no complication of pericardial effusion caused by RV lead extraction. CONCLUSION: RVG for identification of RV lead perforation leads to fewer false-positives compared to non-ECG-gated CT. However, even in cases in which lead perforation is diagnosed, most leads may be safely extracted by transvenous lead extraction.

DOI： 10.1371/journal.pone.0245502

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/ehf2.13318

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/ehf2.13473

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/ejhf.2190

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1536/ihj.20-537

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ijcard.2021.10.150

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記述言語：英語  

DOI： 10.1186/s12933-020-01181-7

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担当区分：最終著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   出版者・発行元：(一社)日本救急医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Preoperative chemoradiation therapy (CRT) has been considered as an effective treatment for non-small cell lung cancer. However, there is concern that CRT progresses atherosclerosis in cancer survivors. This study sought to determine if preoperative CRT exacerbated thoracic aortic calcification (TAC) detected by computed tomography (CT) in patients with lung cancer. Among 473 patients who underwent surgery for lung cancer at Okayama University Hospital between 2011 and 2015, 34 patients undergoing preoperative CRT and surgery (CRT group) and 33 matched patients undergoing initial surgery (non-CRT group) were analyzed and compared. The volume of TAC between the 2nd and 12th thoracic vertebrae was quantitatively measured by CT at baseline and 1-year follow-up. Patients in the CRT group (62 ± 7 years old, 74% male) received cisplatin chemotherapy with docetaxel or vinorelbine and radiation therapy (mean 47.3 ± 4.0 Gy). The percent change in TAC volume was significantly greater in the CRT compared with the non-CRT group (58.7%, 95% confidence interval [CI] 41.7-75.7% vs. 27.2%, 95% CI 9.9-44.4%; p = 0.01). Multivariate logistic regression analysis identified CRT as an independent factor associated with greater TAC progression (> the median value) (odds ratio 3.63, 95% CI 1.19-11.08; p = 0.02). In conclusion, preoperative CRT for lung cancer exacerbates TAC. Follow-up of such patients should thus include careful longitudinal assessment for cardiovascular disease.

DOI： 10.1007/s00380-020-01611-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Statins suppress the progression of atherosclerosis by reducing low-density lipoprotein (LDL) cholesterol levels. Pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor α modulator, is expected to reduce residual risk factors including high triglycerides (TGs) and low high-density lipoprotein (HDL) cholesterol during statin treatment. However, it is not known if statin therapy with add-on pemafibrate improves the progression of atherosclerosis. The aim of this study was to assess the effect of combination therapy with pitavastatin and pemafibrate on lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. METHODS: Seven-week-old male Dahl salt-sensitive (DS) rats were divided into the following five treatment groups (normal diet (ND) plus vehicle, high-salt and high-fat diet (HD) plus vehicle, HD plus pitavastatin (0.3 mg/kg/day), HD plus pemafibrate (K-877) (0.5 mg/kg/day), and HD plus combination of pitavastatin and pemafibrate) and treated for 12 weeks. At 19 weeks, endothelium-dependent relaxation of the thoracic aorta in response to acetylcholine was evaluated. RESULTS: After feeding for 12 weeks, systolic blood pressure and plasma levels of total cholesterol were significantly higher in the HD-vehicle group compared with the ND-vehicle group. Combination therapy with pitavastatin and pemafibrate significantly reduced systolic blood pressure, TG levels, including total, chylomicron (CM), very LDL (VLDL), HDL-TG, and cholesterol levels, including total, CM, VLDL, and LDL-cholesterol, compared with vehicle treatment. Acetylcholine caused concentration-dependent relaxation of thoracic aorta rings that were pre-contracted with phenylephrine in all rats. Relaxation rates in the HD-vehicle group were significantly lower compared with the ND-vehicle group. Relaxation rates in the HD-combination of pitavastatin and pemafibrate group significantly increased compared with the HD-vehicle group, although neither medication alone ameliorated relaxation rates significantly. Western blotting experiments showed increased phosphorylated endothelial nitric oxide synthase protein expression in aortas from rats in the HD-pemafibrate group and the HD-combination group compared with the HD-vehicle group. However, the expression levels did not respond significantly to pitavastatin alone. CONCLUSIONS: Combination therapy with pitavastatin and pemafibrate improved lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. Pemafibrate as an add-on strategy to statins may be useful for preventing atherosclerosis progression.

DOI： 10.1186/s12933-020-01132-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Effects of sodium-glucose cotransporter 2 inhibitors on reducing hospitalization for heart failure have been reported in randomized controlled trials, but their effects on patients with heart failure with preserved ejection fraction (HFpEF) are unknown. This study aimed to evaluate the drug efficacy of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with type 2 diabetes mellitus and HFpEF. Methods and Results We performed a multicenter, open-label, randomized, controlled trial for comparing luseogliflozin 2.5 mg once daily with voglibose 0.2 mg 3 times daily in patients with type 2 diabetes mellitus suffering from HFpEF (left ventricular ejection fraction >45% and BNP [B-type natriuretic peptide] concentrations ≥35 pg/mL) in a 1:1 randomization fashion. The primary outcome was the difference from baseline in BNP levels after 12 weeks of treatment between the 2 drugs. A total of 173 patients with diabetes mellitus and HFpEF were included. Of these, 83 patients were assigned to receive luseogliflozin and 82 to receive voglibose. There was no significant difference in the reduction in BNP concentrations after 12 weeks from baseline between the 2 groups. The ratio of the mean BNP value at week 12 to the baseline value was 0.79 in the luseogliflozin group and 0.87 in the voglibose group (percent change, -9.0% versus -1.9%; ratio of change with luseogliflozin versus voglibose, 0.93; 95% CI, 0.78-1.10; P=0.26). Conclusion In patients with type 2 diabetes mellitus and HFpEF, there is no significant difference in the degree of reduction in BNP concentrations after 12 weeks between luseogliflozin and voglibose. Registration URL: https://www.umin.ac.jp/ctr/index.htm; Unique identifier: UMIN000018395.

DOI： 10.1161/JAHA.119.015103

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担当区分：責任著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Arterial calcification is a hallmark of advanced atherosclerosis and predicts cardiovascular events. However, there is no clinically accepted therapy that prevents progression of arterial calcification. HMG-CoA reductase inhibitors, statins, lower low-density lipoprotein-cholesterol and reduce cardiovascular events, but coronary artery calcification is actually promoted by statins. The addition of eicosapentaenoic acid (EPA) to statins further reduced cardiovascular events in clinical trials, JELIS and REDUCE-IT. Additionally, we found that EPA significantly suppressed arterial calcification in vitro and in vivo via suppression of inflammatory responses, oxidative stress and Wnt signaling. However, so far there is a lack of evidence showing the effect of EPA on arterial calcification in a clinical situation. We reviewed the molecular mechanisms of the inhibitory effect of EPA on arterial calcification and the results of some clinical trials.

DOI： 10.3390/ijms21155455

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

DOI： 10.1016/j.jcmg.2020.01.022

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担当区分：責任著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

Thoracic aortic dissection (TAD) is a life-threatening vascular disease. We showed that CD44, a widely distributed cell surface adhesion molecule, has an important role in inflammation. In this study, we examined the role of CD44 in the development of TAD. TAD was induced by the continuous infusion of β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, and angiotensin II (AngII) for 7 days in wild type (WT) mice and CD44 deficient (CD44-/-) mice. The incidence of TAD in CD44-/- mice was significantly reduced compared with WT mice (44% and 6%, p < 0.01). Next, to evaluate the initial changes, aortic tissues at 24 hours after BAPN/AngII infusion were examined. Neutrophil accumulation into thoracic aortic adventitia in CD44-/- mice was significantly decreased compared with that in WT mice (5.7 ± 0.3% and 1.6 ± 0.4%, p < 0.01). In addition, BAPN/AngII induced interleukin-6, interleukin-1β, matrix metalloproteinase-2 and matrix metalloproteinase-9 in WT mice, all of which were significantly reduced in CD44-/- mice (all p < 0.01). In vitro transmigration of neutrophils from CD44-/- mice through an endothelial monolayer was significantly decreased by 18% compared with WT mice (p < 0.01). Our findings indicate that CD44 has a critical role in TAD development in association with neutrophil infiltration into adventitia.

DOI： 10.1038/s41598-020-63824-9

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掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of transdermal β-blocker patches, which offer stable blood concentration and easy availability during operation, for prevention of perioperative myocardial injury (PMI) in high-risk patients.Methods and Results:In this randomized controlled trial, patients aged >60 years with hypertension and high revised cardiac risk index (≥2) undergoing non-cardiac surgery were randomly assigned to a bisoprolol patch or control group. Primary efficacy outcome was incidence of PMI, defined as postoperative high-sensitivity cardiac troponin T (hs-cTnT) >0.014ng/mL and relative hs-cTnT change ≥20%. Secondary efficacy outcomes were number of cardiovascular events and 30-day mortality. From November 2014 to February 2019, 240 patients from 5 hospitals were enrolled in this study. The incidence of PMI was 35.7% in the bisoprolol patch group and 44.5% in the control group (P=0.18). Incidence of major adverse cardiac events including non-critical myocardial infarction, strokes, decompensated heart failure and tachyarrhythmia was similar between the 2 groups. Tachyarrhythmia tended to be higher in the control group. There were no significant differences in safety outcomes including significant hypotension and bradycardia requiring any treatment between the 2 groups. CONCLUSIONS: Bisoprolol patches do not influence the incidence of PMI and cardiovascular events in high-risk patients undergoing non-cardiac surgery, but perioperative use of these patches is safe.

DOI： 10.1253/circj.CJ-19-0871

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担当区分：筆頭著者   記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Multiple spikes in the QRS complex (fragmented QRS [fQRS]) on 12-lead electrocardiography have been associated with ventricular arrhythmic events (VAEs) in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to assess the association between new appearances of fQRS and cardiac events in patients with HCM.Methods and Results:The association between baseline fQRS and cardiac events, namely VAEs, heart failure-related hospitalization, and all-cause death, was evaluated retrospectively in 146 HCM patients (46 patients with fQRS, 100 without fQRS). The median follow-up was 5.3 years. Cardiac events occurred in 29 patients with baseline fQRS and 32 patients without baseline fQRS (63% vs. 32%; P<0.001). VAEs occurred in a significantly larger percentage of patients with than without baseline fQRS (54% vs. 23%, respectively; P<0.001). Of the 100 patients without baseline fQRS, 33 had a new appearance of fQRS during the 4.6-year follow-up, whereas 67 did not. VAEs occurred more frequently in the 33 patients with the appearance of fQRS than in those without (42% vs. 13%, respectively; P=0.001). Multivariable analysis showed that the new appearance of fQRS documented before VAEs was associated with VAEs (hazard ratio 4.29, 95% confidence interval 1.81-10.2; P=0.001). CONCLUSIONS: The new appearance of fQRS was associated with an increased risk of VAEs in HCM patients.

DOI： 10.1253/circj.CJ-19-0968

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: In heart failure (HF) patients implanted with high-energy devices, worsening of HF can be diagnosed from intrathoracic impedance (ITI) before symptoms appear. Early therapeutic intervention can prevent HF worsening, but the optimal intervention remains unknown. This study aimed to examine which lifestyle modifications or medications can improve HF indicators in asymptomatic HF patients diagnosed from ITI.Methods and Results:This multicenter, prospective, randomized study included patients with high-energy devices, left ventricular ejection fraction <40%, or with a history of HF hospitalization. After the OptiVol alert was evoked by decreased ITI, patients underwent examinations. If they were diagnosed with HF, they were randomly assigned to 3 groups: lifestyle modification, diuretic, or nitrate. After 1 week, they underwent the same examinations. The primary endpoint was change in ITI and serum B-type natriuretic peptide (BNP). Totally, 57 patients were randomized. In all 3 groups, ITI was significantly increased post-intervention compared with pre-intervention. In the diuretic and nitrate groups, logBNP post-intervention was significantly lower than pre-intervention, but not in the lifestyle modification group. CONCLUSIONS: Compared with lifestyle modifications, diuretic and nitrate therapy for 1 week may be more effective management of HF detected by decreased ITI. However, lifestyle modification may have the additional benefits of reducing the workload or cost.

DOI： 10.1253/circj.CJ-19-0986

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   出版者・発行元：日本成人先天性心疾患学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1536/ihj.19-419

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In order to prevent ischemic stroke, it is important to identify and treat patients with atrial fibrillation (AF) who do not consult a doctor in a medical institution. The aim of this study was to determine the consultation rate at medical institutions for patients with AF in group medical examinations conducted in a city in western Japan. Of 6101 examinees of group medical examinations (40 years of age or older) conducted in Ibara City, Okayama Prefecture, Japan, from 2012 to 2014, 4338 participants (71.1%) who were evaluated by electrocardiogram (ECG) gave written informed consent and responded to surveys in the form of questionnaires through a personal interview conducted by nurses were included in the Ibara-AF study. A cumulative total of 82 subjects were diagnosed as having AF by ECG (prevalence of AF = 1.89%), and 51 individuals had AF during the three-year period.15 (29.4%) of the 51 patients with AF did not regularly visit medical institutions. Among them, 46.7% (n = 7) and 53.3% (n = 8) of the patients were symptomatic and asymptomatic, respectively, and 73.3% of the patients had a CHADS2 score of more than one point. There were no significant differences in patients' characteristics between regular and non-regular visit groups. In conclusion, about one-third of the patients with AF did not regularly see a doctor in a medical institution and most of them had a CHADS2 score of more than one point in a Japanese rural area. Educating the public about the risks of AF is required.

DOI： 10.1536/ihj.19-062

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

<title>Abstract</title>
<sec>
<title>Aims</title>
There is no valid treatment strategy for addressing paroxysmal atrial fibrillation (AF) in patients with unclosed atrial septal defect (ASD). We aimed to assess the efficacy of catheter ablation (CA) compared with transcatheter ASD closure alone for treating pre-existing paroxysmal AF in patients with ASD.


</sec>
<sec>
<title>Methods and results</title>
Among 908 patients who underwent transcatheter ASD closure, we evaluated 50 consecutive patients (63 ± 12 years) with paroxysmal AF. We compared the AF outcomes of these patients after transcatheter ASD closure between those with and without CA prior to ASD closure. Thirty (60%) patients underwent CA. During the follow-up period after ASD closure (mean: 49 ± 23 months), recurrence of AF was observed in 6/30 (20%) patients with upfront CA and 12/20 (60%) patients with ASD closure alone. Kaplan–Meier analysis showed that the AF-free survival rate was significantly higher for patients with CA than for those with ASD closure alone (79% vs. 37% at 5 years, P = 0.002). Upfront CA and previous heart failure hospitalization were associated with recurrence of AF after ASD closure [hazard ratio (HR) 0.18, 95% confidence interval (CI) 0.06–0.53; P = 0.002 and HR 4.64, 95% CI 1.60–13.49; P = 0.005, respectively].


</sec>
<sec>
<title>Conclusion</title>
In ASD patient with paroxysmal AF, transcatheter ASD closure alone demonstrated high AF recurrence rate after ASD closure. On the other hand, upfront CA prior to ASD closure substantially suppressed AF recurrence over the long term. A combination of CA and transcatheter ASD closure may be a feasible treatment strategy for paroxysmal AF in patients with ASD.


</sec>

DOI： 10.1093/europace/euz207

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記述言語：英語  

DOI： 10.1016/j.jjcc.2019.05.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE Publications Ltd  

DOI： 10.1177/2045894019896677

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective Remote monitoring (RM) of cardiac implantable electric devices (CIEDs) has been advocated as a healthcare standard. However, expert consensus statements suggest that all patients require annual face-to-face follow-up consultations at outpatient clinics even if RM reveals no episodes. The objective of this study was to determine the critical event rate after CIED implantation through RM. Methods This multicenter, retrospective, cohort study evaluated patients with pacemakers (PMs), implantable cardioverter defibrillators (ICDs), or cardiac resynchronization therapy defibrillator (CRT-Ds) and analyzed whether or not the data drawn from RM included abnormal or critical events. Patients A total of 1,849 CIED patients in 12 hospitals who were followed up by the RM center in Okayama University Hospital were included in this study. Results During the mean follow-up period of 774.9 days, 16,560 transmissions were analyzed, of which 11,040 (66.7%) were abnormal events and only 676 (4.1%) were critical events. The critical event rate in the PM group was significantly lower than that in the ICD or CRT-D groups (0.9% vs. 5.0% or 5.9%, p<0.001). A multivariate analysis revealed that ICD, CRT-D, and a low ejection fraction were independently associated with critical events. In patients with ICD, the independent risk factors for a critical event were old age, low ejection fraction, Brugada syndrome, dilated phase hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. Conclusion Although abnormal events were observed in two-thirds of the transmitted RM data, the critical event rate was <1% in patients with a PM, which was lower in comparison to the rates in patients with ICDs or CRT-Ds. A low ejection fraction was an independent predictor of critical events.

DOI： 10.2169/internalmedicine.1905-18

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The increase in the use of cardiac implantable electronic devices (CIEDs) has been associated with an increase in CIED-related infections. Transvenous lead extraction is safe and effective for patients with CIED-related infections; however, the mortality rate in these patients is high. The prognosis after transvenous lead extraction in Japanese patients, especially those with lead-related infective endocarditis, has not been evaluated. Then, the purpose of this study is to clarify the prognosis after transvenous lead extraction in Japanese patients with CIED-related infections at a single Japanese center. METHODS: A total of 107 patients who underwent transvenous lead extraction were retrospectively reviewed. The patients were divided into a lead-related infective endocarditis group (n = 32) and a pocket infection group (n = 75). Procedure success rate and prognosis after lead extraction were evaluated between the two groups. RESULTS: Procedure success rate was not significantly different between the groups. There were no deaths associated with the procedure or with infection. The survival rate was not significantly different at 1 year or at a median of 816 days (lead-related infective endocarditis vs pocket infection; 93.7% vs 94.7%, P = 1.000; 78.1% vs 81.3%, P = 0.791) Time to reimplantation and duration of hospital stay and antibiotics therapy were significantly longer for patients with lead-related infective endocarditis. CONCLUSION: In this study, the prognosis for patients with lead-related infective endocarditis after transvenous lead extraction was favorable. Thus, extraction should be strongly recommended, even if the general condition of the patient is poor.

DOI： 10.1002/joa3.12164

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Recent large clinical trials failed to show clear benefits of percutaneous transluminal renal angioplasty (PTRA) as compared with medical therapy on patients with renal artery stenosis. It was also reported that proteinuria is an adverse prognostic factor after PTRA, and PTRA is less effective in patients with overt proteinuria. From the renoprotective point of view, to reduce proteinuria after PTRA is an important therapeutic goal in patients with renal artery stenosis with overt proteinuria. We hereby describe two patients successfully treated by combination therapy with PTRA and administration of angiotensin-converting enzyme (ACE) inhibitor for bilateral renal artery disease with overt proteinuria.

DOI： 10.2169/internalmedicine.2076-18

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE OF REVIEW: To summarize the current status of coronary computed tomography angiography (CTA) in the assessment of coronary plaques and discuss the ability of serial coronary CTA to quantitatively measure changes in the plaque burden in response to lipid-lowering therapy. RECENT FINDINGS: Recent advances in coronary CTA have allowed identification of high-risk coronary features in acute coronary syndrome and measurement of changes in the coronary plaque burden with good reproducibility. Statin therapy may delay plaque progression and change some plaque features. However, the clinical relevance of quantitative changes in coronary plaques and the optimal methods to reduce the plaque burden remain unclear. Despite guideline-directed lipid-lowering therapy, adverse events still occur in substantial numbers of patients receiving statins. Coronary CTA is noninvasive and has high diagnostic performance in patients with coronary artery disease, making change in the plaque burden an applicable biomarker for individualized assessment of future risk.

DOI： 10.1007/s11886-019-1170-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are drugs for diabetes and might prevent heart failure. In this study, we investigated the effects of tofogliflozin, an SGLT2 inhibitor, on cardiac hypertrophy and metabolism in hypertensive rats fed a high-fat diet. Dahl salt-sensitive (DS) rats, hypertensive model rats, and Dahl salt-resistant (DR) rats, non-hypertensive model rats, were fed a high-salt and high-fat diet containing tofogliflozin (0.005%) for 9 weeks to examine the effects of this drug on cardiac hypertrophy and metabolism. Tofogliflozin tended to suppress a rise of the systolic blood pressure, relative to the control, throughout the treatment period in both DR and DS rats, and significantly suppress a rise of the systolic blood pressure, relative to the control, at the 9th week in DS rats. Tofogliflozin reduced cardiac hypertrophy (heart weight/body weight) not only in DS rats but also in DR rats. Histological analysis showed that tofogliflozin significantly decreased cardiomyocyte hypertrophy and perivascular fibrosis in both DS and DR rats. Tofogliflozin significantly decreased the expression levels of genes related to cardiac hypertrophy (encoding for natriuretic peptides A and B and interleukin-6), and to cardiac fibrosis (encoding for transforming growth factor-β1 and collagen type IV), in DS rats. Recent studies have shown that hypertrophied and failing hearts shift to oxidizing ketone bodies as a significant fuel source. We also performed metabolome analysis for ventricular myocardial tissue. Tofogliflozin reduced 3-hydroxybutyrate, a ketone body, and significantly decreased the expression levels of β-hydroxybutyrate dehydrogenase 1 and 3-oxoacid CoA-transferase, which are related to ketone oxidization. In conclusion, tofogliflozin ameliorated cardiac hypertrophy and fibrosis along with reduction of ketone usage in myocardial tissue.

DOI： 10.1536/ihj.18-392

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記述言語：英語  

DOI： 10.1038/s41440-019-0225-7

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記述言語：英語  

DOI： 10.1016/j.hrcr.2019.01.012

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記述言語：日本語   出版者・発行元：日本下肢救済・足病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Atrial fibrillation (AF) frequently coexists with cardiovascular disease (CAD) in a clinical setting. However, the optimum therapy for AF patients who have concomitant CAD is unclear. We retrospectively examined the efficacy and safety of radiofrequency catheter ablation (RFCA) prior to percutaneous coronary intervention (PCI) in patients with AF who had concomitant stable CAD. Between January 2014 and December 2015, a total 264 patients (179 men; mean age, 65.5 ± 10.1 years) who were referred to undergo a first RFCA procedure were reviewed in this study. Of the 264 patients, 41 (15.5%) had stable CAD detected by multi-detector computed tomography before RFCA. Thirty-seven patients who had AF with stable CAD were divided into two treatment arms: (1) RFCA prior to PCI (n = 13) and (2) PCI prior to RFCA (n = 24) [four patients excluded because of left main coronary artery disease (LMCA) or triple vessel disease (TVD)]. The median follow-up was 14 (IQR 8-19) months. There was no significant difference in AF recurrence rate after the procedure between the RFCA first group and PCI first group (P = 0.515). No symptomatic cardiovascular events occurred the during follow-up period. The PCI first group had a significantly longer duration of triple therapy (188.5 ± 167 days vs 5.6 ± 24.5 days, P = 0.01) and all of the four bleeding events occurred during triple therapy (P = 0.01). The results of this single-center pilot study suggested that prior RFCA in patients with AF coexisting with CAD could have fewer serious bleeding events than prior PCI.

DOI： 10.1007/s00380-018-1280-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: Oxidized high-density lipoprotein (oxHDL) is characterized by reduced anti-inflammatory properties compared with HDL. However, the role of oxHDL in the pathogenesis of coronary artery calcification (CAC), a marker of subclinical atherosclerosis, remains unclear. We prospectively investigated the association between the change in oxHDL and progression of CAC in a substudy of a multicenter study. METHODS: In the principal study, patients with a CAC score of 1-999 were treated with pitavastatin with/without eicosapentaenoic acid. Measurement of CAC with multidetector-row computed tomography and a blood test were performed at baseline and at the 1-year follow-up. In the principal study, the increase in CAC did not differ among treatment groups. In this substudy, patients were divided into two groups: CAC progression (change in Agatston score of >0) and no CAC progression. RESULTS: In total, 140 patients were analyzed. The oxHDL level significantly decreased from 167 (132-246) at baseline to 122 (103-149) after treatment (median [25th-75th percentile], U/ml) (p < 0.001). The annual change in CAC was significantly positively associated with changes in oxHDL (r = 0.17, p = 0.04), triglycerides (r = 0.17, p = 0.04), and high-sensitivity C-reactive protein (r = 0.22, p = 0.01) but was not associated with changes in low-density lipoprotein cholesterol or HDL-cholesterol. Multiple logistic analysis demonstrated that the decrease in oxHDL per 10 U/ml was independently associated with CAC progression (odds ratio, 0.95; 95% confidence interval, 0.90-0.99; p = 0.04). CONCLUSIONS: The decrease in oxHDL is associated with the attenuation of CAC progression, suggesting that oxHDL is a potential target for atherosclerosis prevention.

DOI： 10.1016/j.atherosclerosis.2019.01.032

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: High platelet reactivity before percutaneous coronary intervention (PCI) reportedly increases the risk of PCI-related myocardial infarction (PMI) following elective PCI. We conducted a pilot study to evaluate changes in platelet reactivity during PCI and their association with the incidence of PMI. METHODS: In total, 133 consecutive patients undergoing elective PCI after pretreatment with dual antiplatelet therapy for at least 7 days were prospectively enrolled. Platelet reactivity was measured by the VerifyNow® assay (International Technidyne Corporation, Edison, NJ, USA) immediately before and after PCI. RESULTS: Platelet reactivity significantly increased from 177.3 ± 53.4 P2Y12 reaction units (PRU) before PCI to 203.4 ± 52.8 PRU immediately after PCI (p < 0.001). Absolute changes in platelet reactivity were significantly greater in patients with than without PMI (32.4 ± 29.0 vs. 21.2 ± 24.8 PRU, respectively; p = 0.021). In the multivariable logistic regression analysis, the absolute change in PRU was an independent predictor of the incidence of PMI. Receiver operating characteristic curve analysis of the change in PRU during PCI for discriminating PMI showed a sensitivity, specificity, and the cut-off value of 46%, 76%, and 37 PRU, respectively (area under the curve = 0.607, p = 0.0235). When the patients were divided into two groups, namely a greater (change in PRU ≥ 37) and smaller (change in PRU < 37) increase group, the incidence rate of PMI was significantly higher in the greater than smaller increase group (59.1% vs. 34.8%, respectively; p = 0.008). Additional exploratory analyses by intracoronary imaging demonstrated that the proximal reference lumen area in the greater increase group was significantly smaller than that in the smaller increase group (6.5 ± 2.4 vs. 7.7 ± 3.1 mm2, respectively; p = 0.032). CONCLUSION: An increase in platelet reactivity after elective PCI is possibly associated with PMI. This finding should be validated by a larger-scale study.

DOI： 10.1016/j.jjcc.2018.07.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SAGE Publications Ltd  

DOI： 10.1177/2045894019831217

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Recent clinical studies have shown that treatment with LCZ696, a complex containing the angiotensin receptor blocker valsartan and neprilysin inhibitor sacubitril, improves the prognosis of heart failure patients with a reduced ejection fraction. This study evaluated whether LCZ696 affects left ventricular hypertrophy, fibrosis, and hemodynamics in isoproterenol (ISO)-treated rats compared with valsartan alone. METHODS: Male Wistar rats received subcutaneous saline (n = 10), subcutaneous ISO (2.4 mg/kg/day; n = 10), subcutaneous ISO + oral LCZ696 (60 mg/kg/day; n = 20) (ISO-LCZ), or subcutaneous ISO + oral valsartan (30 mg/kg/day; n = 20) (ISO-VAL) for 7 days. RESULTS: LCZ696 and valsartan did not significantly reduce the increased heart weight/body weight ratio in rats treated with ISO. Echocardiography showed that the deceleration time shortened by ISO was restored by LCZ696 but not valsartan alone (p = 0.01 vs. the ISO group). Histological analysis showed that cardiac interstitial fibrosis increased by ISO was decreased significantly by LCZ696 but not valsartan alone (control: 0.10 ± 0.14%; ISO: 0.41 ± 0.32%; ISO-LCZ: 0.19 ± 0.23% [p < 0.01 vs. the ISO group]; ISO-VAL: 0.34 ± 0.23% [p = 0.34 vs. the ISO group]). Quantitative polymerase chain reaction showed that mRNA expression of Tgfb1, Col1a1, Ccl2, and Anp increased by ISO was significantly attenuated by LCZ696 but not valsartan alone (p < 0.05 vs. the ISO group). CONCLUSIONS: LCZ696 improves cardiac fibrosis, but not hypertrophy, caused by continuous exposure to ISO in rats.

DOI： 10.5603/CJ.a2018.0048

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0212889

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1253/circj.CJ-19-0811

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DOI： 10.1016/j.jcin.2018.06.055

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記述言語：英語  

DOI： 10.1016/j.jns.2018.08.015

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Cardiac sarcoidosis (CS) is a noncaseating granulomatous disease of unknown etiology. Lifelong immunosuppressive therapy, most frequently using corticosteroids, is a standard therapy to control hypersensitivity of immune reactions and prevent inflammation. However, it sometimes causes various systemic adverse effects and requires dose escalation. Thus, additional therapy may be required for the treatment of this disease. Recently, Propionibacterium acnes (P. acnes) was reported as one of the etiologic agents of CS, indicating that antibacterial drugs (ABD) may be effective for the treatment of CS. The objective of this study was to investigate the effect of ABD treatment, in addition to standard corticosteroid therapy, in patients with CS. Methods: The Japanese Antibacterial Drug Management for Cardiac Sarcoidosis (J-ACNES) trial was designed as a prospective, multicenter, randomized, open-label, controlled clinical trial. The patients will be randomized to receive either standard corticosteroid therapy plus ABD therapy (ABD group) or standard corticosteroid therapy (standard group). The primary endpoint is change in the total standardized uptake value at 6 months vs baseline using fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography. Secondary endpoints include efficacy, prognosis, and safety. Results: The results of this study are currently under investigation. Conclusion: The J-ACNES trial will be the first prospective study assessing the clinical benefit and safety of ABD therapy, in addition to corticosteroid treatment, in patients with CS. Our findings may improve treatment of patients with CS, as additional ABD therapy reduces recurrence of inflammation and elucidates the mechanism of sarcoidosis.

DOI： 10.1002/joa3.12084

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記述言語：日本語   出版者・発行元：(一社)日本脈管学会  

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記述言語：英語  

DOI： 10.1016/j.jjcc.2018.03.005

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DOI： 10.1016/j.ijcard.2018.02.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier Inc  

DOI： 10.1016/j.jacep.2018.02.009

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記述言語：日本語   出版者・発行元：日本下肢救済・足病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Lipoprotein(a), or Lp(a), is a low-density lipoprotein-like particle largely independent of known risk factors for, and predictive of, cardiovascular disease (CVD). We investigated the association between baseline Lp(a) levels and the progression of coronary artery calcification (CAC) in patients with hypercholesterolemia undergoing statin therapy. This study was a sub-analysis of a multicenter prospective study that evaluated the annual progression of CAC under intensive and standard pitavastatin treatment with or without eicosapentaenoic acid in patients with an Agatston score of 1 to 999, and hypercholesterolemia treated with statins. We classified the patients into 3 groups according to CAC progression. A total of 147 patients (mean age, 67 years; men, 54%) were analyzed. The proportion of patients with Lp(a) > 30 mg/dL significantly increased as CAC progressed (non-progression; 5.4%, 0<CAC progression ≦100; 7.7%, and CAC progression >100; 23.6%). Logistic regression analysis showed that Lp(a) > 30 mg/dL was an independent predictor of the annual change in Agatston score > 100 (OR: 5.51; 95% CI: 1.28-23.68; p=0.02), even after adjusting for age, sex, hypertension, diabetes mellitus, current smoking, body mass index, and lipid-lowering medications. Baseline Lp(a) >30 mg/dL was a predictor of CAC progression in this population of patients with hypercholesterolemia undergoing statin therapy.

DOI： 10.18926/AMO/56067

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記述言語：英語  

Introduction: Recent advances in pulmonary arterial hypertension (PAH)-specific drugs have dramatically changed the therapeutic strategy for PAH. A strategy that includes 'treatment' with PAH-specific drugs initially and then 'repair' by closure of the cardiac defect (i.e. 'treat and repair') was devised, and has been attempted, in patients with PAH associated with a cardiac defect. Case presentation: We present three cases of severe PAH associated with a ventricular septal defect (VSD) in adult patients who were initially treated with PAH-specific drugs followed by VSD closure. Two of the patients were treated with a combination of an endothelin receptor antagonist (ERA), phosphodiesterase type 5 inhibitor, and intravenous prostacyclin before VSD closure. The third patient was treated with an ERA and pulmonary artery banding before VSD closure. After 12 months of anti-PAH treatment, the pulmonary vascular resistance index and the ratio of the pulmonary vascular index to the systemic vascular resistance index decreased to levels that allowed VSD closure. At the mid- and long-term follow-up measurements after surgical closure of the VSD, the mean pulmonary artery pressure had markedly decreased. Discussion: Our case series suggests that the treat-and-repair strategy is a promising approach for adult patients with severe PAH associated with VSD.

DOI： 10.1093/ehjcr/yty033

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A biological pacemaker is expected to solve the persisting problems of an artificial cardiac pacemaker including short battery life, lead breaks, infection, and electromagnetic interference. We previously reported HCN4 overexpression enhances pacemaking ability of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs) in vitro. However, the effect of these cells on bradycardia in vivo has remained unclear. Therefore, we transplanted HCN4-overexpressing mESC-CMs into bradycardia model animals and investigated whether they could function as a biological pacemaker. The rabbit Hcn4 gene was transfected into mouse embryonic stem cells and induced HCN4-overexpressing mESC-CMs. Non-cardiomyocytes were removed under serum/glucose-free and lactate-supplemented conditions. Cardiac balls containing 5 × 103 mESC-CMs were made by using the hanging drop method. One hundred cardiac balls were injected into the left ventricular free wall of complete atrioventricular block (CAVB) model rats. Heart beats were evaluated using an implantable telemetry system 7 to 30 days after cell transplantation. The result showed that ectopic ventricular beats that were faster than the intrinsic escape rhythm were often observed in CAVB model rats transplanted with HCN4-overexpressing mESC-CMs. On the other hand, the rats transplanted with non-overexpressing mESC-CMs showed sporadic single premature ventricular contraction but not sustained ectopic ventricular rhythms. These results indicated that HCN4-overexpressing mESC-CMs produce rapid ectopic ventricular rhythms as a biological pacemaker.

DOI： 10.1536/ihj.17-241

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Portopulmonary hypertension (POPH) is characterized by pulmonary vasoconstriction, while hepatopulmonary syndrome (HPS) is characterized by vasodilation. Definite POPH is a risk factor for the survival after orthotopic liver transplantation (OLT), as the congestive pressure affects the grafted liver, while subclinical pulmonary hypertension (PH) has been acknowledged as a non-risk factor for deceased donor OLT. Given that PH measurement requires cardiac catheterization, the tricuspid regurgitation pressure gradient (TRPG) measured by echocardiography is used to screen for PH and congestive pressure to the liver. We investigated the impact of a subclinical high TRPG on the survival of small grafted living donor liver transplantation (LDLT). METHODS: We retrospectively analyzed 84 LDLT candidates. Patients exhibiting a TRPG ≥25 mmHg on echocardiography were categorized as potentially having liver congestion (subclinical high TRPG; n = 34). The mean pulmonary artery pressure (mPAP) measured after general anesthesia with FIO20.6 (mPAP-FIO20.6) was also assessed. Patients exhibiting pO2 < 80 mmHg and an alveolar-arterial oxygen gradient (AaDO2) ≥ 15 mmHg were categorized as potentially having HPS (subclinical HPS; n = 29). The clinical course after LDLT was investigated according to subclinical high TRPG. RESULTS: A subclinical high TRPG (p = 0.012) and older donor age (p = 0.008) were correlated with a poor 40-month survival. Although a higher mPAP-FIO20.6 was expected to correlate with a worse survival, a high mPAP-FIO20.6 with a low TRPG was associated with high frequency complicating subclinical HPS and a good survival, suggesting a reduction in the PH pressure via pulmonary shunt. CONCLUSION: In cirrhosis patients, mPAP-FIO20.6 may not accurately reflect the congestive pressure to the liver, as the pressure might escape via pulmonary shunt. A subclinical high TRPG is an important marker for predicting a worse survival after LDLT, possibly reflecting congestive pressure to the grafted small liver.

DOI： 10.1186/s12876-018-0793-z

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記述言語：日本語   出版者・発行元：臨床心臓電気生理研究会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1161/CIRCGEN.118.002103

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Platypnea-orthodeoxia syndrome (POS) is a rare condition that is characterized by dyspnea and arterial oxygen desaturation, which worsen on standing and which are relieved by recumbency. We treated an 80-year-old woman with an atrial septal defect (ASD) who demonstrated POS following thoracic and lumbar vertebral compression fractures. The surgical closure of the ASD relieved her symptoms. The etiology might have been multiple compression fractures causing kyphosis and aortic distortion producing right atrial compression and increased right-to-left flow through the ASD. POS should be considered in the differential diagnosis of patients who develop dyspnea after vertebral compression fractures. The careful assessment of the patient's history and clinical condition helps in the diagnosis of POS.

DOI： 10.2169/internalmedicine.9904-17

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Public Library of Science  

DOI： 10.1371/journal.pone.0193695

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) is useful for detecting myocardial injury and is expected to become a prognostic marker in patients undergoing non-cardiac surgery. The aim of this pilot study evaluating the efficacy of β-blocker therapy in a perioperative setting (MAMACARI study) was to assess perioperative myocardial injury (PMI) in elderly patients with preserved ejection fraction (EF) undergoing non-cardiac surgery.Methods and Results:In this prospective observational cohort study of 151 consecutive patients with preserved EF and aged >60 years who underwent non-cardiac surgery, serum levels of hs-cTnT were measured before and on postoperative days 1 and 3 after surgery. PMI was defined as postoperative hs-cTnT >0.014 ng/mL and relative hs-cTnT change ≥20%. A total of 36 (23.8%) of the patients were diagnosed as having PMI. The incidence of a composite of cardiovascular events within 30 days after surgery, including myocardial infarction, stroke, worsening heart failure, atrial fibrillation and pulmonary embolism, was significantly higher in patients with PMI than in patients without PMI (odds ratio (OR) 9.25, P<0.001, 95% confidence interval (CI) 2.65-32.3). Multivariate analysis revealed that left ventricular diastolic dysfunction defined by echocardiography was independently associated with PMI (OR: 3.029, 95% CI: 1.341-6.84, P=0.008). CONCLUSIONS: PMI is frequently observed in elderly patients undergoing non-cardiac surgery. Diastolic dysfunction is an independent predictor of PMI.

DOI： 10.1253/circj.CJ-17-0747

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The effect of lipid-lowering agents on progression of coronary artery calcification (CAC) remains unclear. We evaluated the effects of pitavastatin 2 mg/day (PIT2), pitavastatin 4 mg/day (PIT4), and PIT2 combined with eicosapentaenoic acid (PIT2+EPA) on CAC progression.Methods and Results:This prospective multicenter study in Japan included patients with an Agatston score of 1-999, hypercholesterolemia, and no evidence of cardiovascular disease. Patients were allocated into PIT2, PIT4, or PIT2+EPA groups. The primary outcome was the annual percent change in Agatston score in all patients. In total, 156 patients who had multi-detector row computed tomography without any artifacts were included in the primary analysis. Pitavastatin did not significantly reduce the annual progression rate of the Agatston score (40%; 95% CI: 19-61%). The annual progression rate of Agatston score in the PIT2 group was not significantly different from that in the PIT4 group (34% vs. 42%, respectively; P=0.88) or the PIT2+EPA group (34% vs. 44%, respectively; P=0.80). On post-hoc analysis the baseline ratio of low- to high-density lipoprotein cholesterol was a significant predictor of non-progression of Agatston score by pitavastatin (OR, 2.17; 95% CI: 1.10-44.12; P=0.02). CONCLUSIONS: Pitavastatin does not attenuate progression of CAC. Intensive pitavastatin treatment and standard treatment with EPA does not reduce progression of CAC compared with standard treatment.

DOI： 10.1253/circj.CJ-17-0419

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/jce.13336

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese College of Cardiology (Nippon-Sinzobyo-Gakkai)  

DOI： 10.1016/j.jjcc.2018.04.014

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0203046

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掲載種別：研究論文（学術雑誌）  

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掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/ijerph15112575

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記述言語：日本語   出版者・発行元：(一社)日本脈管学会  

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記述言語：日本語   出版者・発行元：(公財)日本心臓財団  

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記述言語：英語  

DOI： 10.1161/CIRCIMAGING.116.005839

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/cnma.201600031

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記述言語：日本語   出版者・発行元：(一社)日本成人先天性心疾患学会  

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掲載種別：研究論文（学術雑誌）  

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DOI： 10.1093/europace/euu371

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記述言語：日本語   出版者・発行元：(一社)日本脈管学会  

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記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Springer International Publishing  

DOI： 10.1007/978-94-007-7696-8_44

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記述言語：英語   掲載種別：論文集(書籍)内論文   出版者・発行元：Nova Science Publishers, Inc.  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: No study has investigated whether pioglitazone (an agonist of peroxisome proliferator-activated receptor gamma) protects against ischemia and reperfusion (IR)-induced endothelial dysfunction in humans. METHODS AND RESULTS: In the first crossover study, 20 volunteers were randomized to 1 week of pioglitazone (30 mg/d, postoperatively) or control (no treatment). In the second single-arm study, 15 volunteers received pioglitazone and the cyclooxygenase-2 inhibitor meloxicam for 1 week. On day 7, endothelium-dependent flow-mediated dilation (FMD) of the distal brachial artery was measured before and after IR (15 minutes of ischemia followed by 15 minutes of reperfusion in the proximal upper arm). Pre-IR brachial-artery diameter and FMD were similar across the 2 sessions (control, pioglitazone) in protocol 1 and between the 2 protocols. IR significantly blunted FMD after no treatment (pre-IR FMD: 10.2% ± 2.6%; post-IR FMD: 3.5% ± 1.9%, P < 0.01) but not after pioglitazone administration (pre-IR FMD: 9.7% ± 2.5%; post-IR FMD: 8.8% ± 2.9%, P = 0.11). This protective effect was accompanied by an increase in serum levels of the antioxidant enzyme extracellular superoxide dismutase and was not affected by concomitant administration of the cyclooxygenase-2 inhibitor meloxicam (P = 0.10). CONCLUSIONS: In humans, pioglitazone provides potent protection against IR-induced endothelial dysfunction.

DOI： 10.1097/FJC.0000000000000124

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Postprandial elevation of triglycerides impairs endothelial function and contributes to the development of atherosclerosis. We investigated the effects of omega-3 fatty acids on postprandial endothelial function and lipid profiles. METHODS: Healthy volunteers [10] were given supplementation at 4g/day omega-3 fatty acids (or were not treated) for 4 weeks in a randomised crossover study. Postprandial levels of various lipids were monitored and endothelial function assessed by brachial artery flow-mediated dilation during fasting and after a standard cookie test. RESULTS: Omega-3 fatty acids reduced postprandial endothelial dysfunction compared with the control diet (flow-mediated dilation at 4h=-0.5±1.2 vs. -2.0±1.6%, P=0.03). Postprandial levels of triglycerides, apolipoprotein B-48, and remnant lipoprotein-cholesterol increased in untreated subjects, peaked at 2-4h, and returned to baseline at 8h, whereas low-density lipoprotein-cholesterol levels did not change. Supplementation with omega-3 fatty acids significantly suppressed postprandial elevation of triglycerides (incremental area under the curve=220±209 vs. 374±216mg/h/dL, P=0.04) and remnant lipoprotein-cholesterol (incremental area under the curve=21.7±13.8 vs. 13.3±12.9mg/h/dL, P=0.04). Supplementation with omega-3 fatty acids significantly suppressed the increase in triglyceride content in chylomicrons as well as in very-low-density lipoproteins from baseline to 4h after the cookie test. CONCLUSION: Omega-3 fatty acids significantly decreased postprandial triglyceride elevation and postprandial endothelial dysfunction, suggesting that omega-3 fatty acids may have vascular protective effects in postprandial state.

DOI： 10.1016/j.biopha.2014.10.008

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s40256-014-0082-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

RATIONALE: Cyclophilin A (CyPA) is secreted from vascular smooth muscle cells (VSMCs) by oxidative stress and promotes VSMC proliferation. However, the role of extracellular CyPA and its receptor Basigin (Bsg, encoded by Bsg) in the pathogenesis of pulmonary hypertension (PH) remains to be elucidated. OBJECTIVE: To determine the role of CyPA/Bsg signaling in the development of PH. METHODS AND RESULTS: In the pulmonary arteries of patients with PH, immunostaining revealed strong expression of CyPA and Bsg. The pulmonary arteries of CyPA(±) and Bsg(±) mice exposed to normoxia did not differ in morphology compared with their littermate controls. In contrast, CyPA(±) and Bsg(±) mice exposed to hypoxia for 4 weeks revealed significantly reduced right ventricular systolic pressure, pulmonary artery remodeling, and right ventricular hypertrophy compared with their littermate controls. These features were unaltered by bone marrow reconstitution. To further evaluate the role of vascular Bsg, we harvested pulmonary VSMCs from Bsg(+/+) and Bsg(±) mice. Proliferation was significantly reduced in Bsg(±) compared with Bsg(+/+) VSMCs. Mechanistic studies demonstrated that Bsg(±) VSMCs revealed reduced extracellular signal-regulated kinase 1/2 activation and less secretion of cytokines/chemokines and growth factors (eg, platelet-derived growth factor-BB). Finally, in the clinical study, plasma CyPA levels in patients with PH were increased in accordance with the severity of pulmonary vascular resistance. Furthermore, event-free curve revealed that high plasma CyPA levels predicted poor outcome in patients with PH. CONCLUSIONS: These results indicate the crucial role of extracellular CyPA and vascular Bsg in the pathogenesis of PH.

DOI： 10.1161/CIRCRESAHA.115.304563

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1136/heartjnl-2013-305468

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記述言語：日本語   出版者・発行元：臨床心臓電気生理研究会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jacc.2014.01.072

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記述言語：英語  

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記述言語：英語  

Idiopathic pulmonary arterial hypertension (IPAH) is characterized by pulmonary vascular remodeling. We have reported that high-dose prostaglandin I2 (PGI2) therapy markedly improved hemodynamics in IPAH patients and that PGI2 induced apoptosis of pulmonary artery smooth muscle cells obtained from IPAH patients. PGI2 is thought to have reverse remodeling effects, although it has not been histologically confirmed. In a case series, we examined the reverse pulmonary vascular remodeling effects of PGI2 in lung tissues obtained from an IPAH patient treated with high-dose PGI2 and an IPAH patient not treated with PGI2. Apoptotic cells were detected in small pulmonary arteries of the IPAH patient treated with high-dose PGI2 but not in those from the IPAH patient not treated with PGI2. Media of peripheral pulmonary arteries were thick in the IPAH patient not treated with PGI2. On the other hand, media of peripheral pulmonary arteries were thin in the IPAH patient treated with high-dose PGI2. The single case report suggested that high-dose PGI2 therapy has the potential for reverse pulmonary vascular remodeling by induction of apoptosis and reduction of medial hypertrophy. Accumulation of cases is needed for the application to generalized effect of high-dose PGI2. <Learning objective: Reverse pulmonary vascular remodeling would provide further improvement in patients with IPAH. High-dose PGI2 therapy has the potential for reverse pulmonary vascular remodeling in patients with IPAH.>.

DOI： 10.1016/j.jccase.2013.12.011

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/1475-2840-13-71

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.atherosclerosis.2014.01.019

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00380-013-0343-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/1475-2840-13-61

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記述言語：日本語   出版者・発行元：(一社)日本成人先天性心疾患学会  

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記述言語：日本語   出版者・発行元：Japan Heart Foundation  

88歳男性. 陳旧性下壁心筋梗塞, バイパス手術・僧帽弁形成術・左室形成術・ICD植込み術後. 2012年12月, VTに対するICD頻回作動で入院. V1のR/S ratio=1で上方軸の薬剤抵抗性VTに対し第1回アブレーション (CA) を施行. 左室の下壁～下壁中隔移行部でのentrainmentでconcealed fusion, 頻拍周期 (TCL) =post pacing interval (PPI), Egm-QRS=Stim-QRSが得られた. 同部の通電でVTは停止しなかったが周囲へ追加通電後にVTは誘発不可能となった. しかし後日同波形のVTが再発. ICD頻回作動を認め第2回CA施行. 中心静脈 (MCV) にてconcealed fusion, TCL=PPI, Egm-QRS=Stim-QRSが得られ, 同部の通電でVT波形は変化. 追加通電後にVT誘発不可能となった. 以後, 同波形のVT再発なく無事退院となった.

DOI： 10.11281/shinzo.46.S3_203

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記述言語：日本語   出版者・発行元：Japan Heart Foundation  

DOI： 10.11281/shinzo.46.812

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その他リンク： http://search.jamas.or.jp/link/ui/2014260969

掲載種別：研究論文（学術雑誌）  

DOI： 10.1254/fpj.143.173

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掲載種別：研究論文（学術雑誌）  

DOI： 10.2957/kanzo.55.143

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記述言語：日本語   出版者・発行元：(公財)日本心臓財団  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J00679&link_issn=&doc_id=20131216220028&doc_link_id=10.11281%2Fshinzo.45.S3_143&url=https%3A%2F%2Fdoi.org%2F10.11281%2Fshinzo.45.S3_143&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

DOI： 10.1016/j.ijcard.2013.07.261

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DOI： 10.1016/j.ijcard.2013.08.011

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J01759&link_issn=&doc_id=20131007210019&doc_link_id=issn%3D0289-8020%26volume%3D34%26issue%3D9%26spage%3D1202&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0289-8020%26volume%3D34%26issue%3D9%26spage%3D1202&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(公財)日本心臓財団  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J00679&link_issn=&doc_id=20130819090020&doc_link_id=10.11281%2Fshinzo.45.S2_91&url=https%3A%2F%2Fdoi.org%2F10.11281%2Fshinzo.45.S2_91&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.hrthm.2013.04.009

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記述言語：英語  

Diastolic dysfunction of the heart is correlated with cardiac mortality. Serum cystatin C (CysC) is an endogenous marker of kidney function. It is not clear whether serum CysC is associated with diastolic dysfunction in patients with varying cardiac conditions with concomitant diastolic abnormalities and preserved ejection fraction (EF). The authors measured serum CysC levels in patients with cardiac diseases and examined the relationships between serum CysC levels and diastolic function. Serum CysC was measured and echocardiography was performed in 124 consecutive patients with cardiac diseases. Transmitral flow (TMF) patterns surrogating diastolic function were categorized into two groups: a normal group and an abnormal group. Serum CysC and BNP showed a significant positive correlation. There were no significant differences in serum CysC among those cardiac diseases. Seventy-eight patients with cardiac disease and preserved EF (left ventricular EF ≥50%) and without renal dysfunction (estimated glomerular filtration rate ≥60 mL/minute/1.73 m(2) ) were examined. Multivariate linear regression analysis demonstrated that left atrium diameter and abnormal TMF patterns were independent determinants of serum CysC. Furthermore, patients with elevated serum CysC levels had poor prognosis. Serum CysC is associated with diastolic dysfunction in patients with various cardiac diseases and preserved EF. Serum CysC might be a biomarker of cardiac diastolic dysfunction in patients with preserved EF.

DOI： 10.1111/chf.12039

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.carpath.2012.12.002

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ijcard.2011.09.004

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/1475-2840-12-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Dual antiplatelet therapy (DAPT) after percutaneous coronary intervention increases the risk of bleeding. We studied the safety and clinical outcomes of switching from DAPT to aspirin monotherapy at 3 months after ZES implantation. We retrospectively evaluated 168 consecutive patients with coronary artery disease who had been implanted with a ZES from June 2009 through March 2010. After excluding 40 patients according to exclusion criteria such as myocardial infarction, 128 patients were divided into a 3-month DAPT group (67 patients, 88 lesions) and a 12-month conventional DAPT group (61 patients, 81 lesions). Coronary angiographic followup and clinical followup were conducted at more than 8 months and at 12 months after ZES implantation, respectively. Minor and major bleeding events, stent thrombosis (ST), and major adverse cardiac events (MACE) (death, myocardial infarction, cerebrovascular accident, target lesion revascularization, and target vessel revascularization) were evaluated. There were no statistically significant differences in the incidences of ST and MACE between the two groups. The incidence of bleeding events was significantly lower in the 3-month group than in the 12-month group (1.5% versus 11.5%, P < 0.05). DAPT can be safely discontinued at 3 months after ZES implantation, which reduces bleeding risk.

DOI： 10.1155/2013/518968

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1253/circj.CJ-12-0995

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0056695

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記述言語：英語   出版者・発行元：The Japanese Circulation Society  

Background: We evaluated the safety and efficacy of a bolus injection of landiolol hydrochloride, an ultrashort-acting β1-selective antagonist, as an additional treatment after premedication with an oral β-blocker to reduce heart rate prior to multidetector-row computed tomography (MDCT) coronary angiography (CAG). Methods and Results: A total of 458 patients who underwent MDCT CAG were retrospectively enrolled. Image quality and hemodynamic parameters were compared in patients before and after approval of landiolol hydrochloride. If heart rate reduction was insufficient after premedication with an oral β-blocker, a bolus injection of landiolol hydrochloride (n=66) or other drugs (n=30) was used. The percentage of evaluable images per segment in patients after approval of landiolol (99.3%) was greater than that in patients before approval of landiolol (97.4%, P<0.01). Heart rates before scanning in patients receiving landiolol hydrochloride were similar to those receiving other drugs. Heart rate was significantly reduced approximately 5min after injection of landiolol hydrochloride and increased shortly. No decrease in systolic blood pressure or other adverse effects was observed. Conclusions: Bolus injection of landiolol hydrochloride sufficiently reduced heart rate without significantly reducing systolic blood pressure and produced a high percentage of evaluable images, suggesting that bolus injection of landiolol hydrochloride as an additional pretreatment is feasible in MDCT CAG.  (Circ J 2013; 77: 146–152)<br>

DOI： 10.1253/circj.CJ-12-0663

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その他リンク： http://search.jamas.or.jp/link/ui/2013357873

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1254/jphs.12114FP

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1161/CIRCEP.111.970285

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：日本語   出版者・発行元：(NPO)日本高血圧学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1253/circj.CJ-11-1455

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s11748-012-0058-7

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ijcard.2011.02.024

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.hrthm.2011.11.045

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記述言語：日本語   出版者・発行元：岡山医学会  

DOI： 10.4044/joma.124.71

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その他リンク： http://ousar.lib.okayama-u.ac.jp/48140

記述言語：日本語   出版者・発行元：(株)医学書院  

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記述言語：日本語   出版者・発行元：日本臨床分子医学会  

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記述言語：日本語   出版者・発行元：(株)ライフ・サイエンス  

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：日本語   出版者・発行元：Japan Heart Foundation  

Brugada症候群（BS）では心室細動が問題となるが，まれに持続性単形性心室頻拍（VT）を起こすことがある．当院で電気生理学的検査を施行したBS 179人中4例にVTが誘発され，うち3例では入院前に動悸発作があった．2例（症例1，2）は右室流出路（左脚ブロックLBBB，下方軸）型VTでR波は症例1ではI，aV_L誘導とも（－），最早期興奮部位は左冠尖にみられた．症例2ではR波はI（+），aV_L（－）で，最早期興奮部位は右室流出路および左冠尖であった．症例1，2とも冠尖内に遅延電位を認め，同部位で通電するも無効であった．症例1では通電中に単形性VTが多形性VTに変化し，術後に心室細動を認めた．VTの機序としては，心外膜側起源で非リエントリー性と考えられた．右脚ブロック（RBBB）+上方軸型VTの2例は，VT中に前プルキンエ電位，プルキンエ電位が記録され，リエントリー性の特発性左室心室頻拍と診断した．<BR>Brugada症候群に伴う持続性VTを4例経験したので報告する．

DOI： 10.11281/shinzo.44.S2_55

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1161/CIRCEP.111.969972

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/j.1440-1827.2011.02779.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12576-011-0172-9

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記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2011&ichushi_jid=J01759&link_issn=&doc_id=20111111100004&doc_link_id=issn%3D0289-8020%26volume%3D32%26issue%3D10%26spage%3D1217&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0289-8020%26volume%3D32%26issue%3D10%26spage%3D1217&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/ph4081088

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.atherosclerosis.2011.04.019

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記述言語：英語  

A 50-year-old man diagnosed with liver cirrhosis type C was referred to our hospital because of right heart failure with pulmonary hypertension. Echocardiography revealed enlargement of the right atrium and ventricle with severe tricuspid regurgitation. The peak flow velocity of tricuspid regurgitation by continuous wave Doppler echocardiography was 452 cm/s. Right heart catheterization demonstrated severe pulmonary hypertension [pulmonary arterial pressure (PAP) systolic/diastolic/mean = 73/20/41 mmHg and pulmonary vascular resistance (PVR) = 509 dyn s cm-5] with portal hypertension. We diagnosed the patient as having portopulmonary hypertension (PoPH). Although we treated the patient with a prostacyclin analog, tricuspid regurgitation velocity was increased to 480 cm/s four years after the start of the therapy. To select drugs for the treatment of PoPH, we performed an acute vasoreactivity test of sildenafil during right heart catheterization. Since single administration of sildenafil (20 mg) decreased PAP (93/30/55-77/27/44 mmHg) and PVR (908-833 dyn s cm-5), we added sildenafil (20 mg, t.i.d.) to the prostacyclin analog. Tricuspid regurgitation velocity decreased to 403 cm/s one year after the addition of sildenafil. An acute vasoreactivity test of sildenafil during right heart catheterization was useful for the decision of the drug to be used in the treatment of PoPH.

DOI： 10.1016/j.jccase.2011.04.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.amjcard.2011.03.049

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.hrthm.2011.02.009

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記述言語：日本語   出版者・発行元：臨床心臓電気生理研究会  

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0019897

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1186/1475-2840-10-44

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DOI： 10.1159/000333801

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掲載種別：研究論文（学術雑誌）   出版者・発行元：1  

DOI： 10.1164/ajrccm.183.1.139

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記述言語：日本語   出版者・発行元：Japan Heart Foundation  

筋緊張性ジストロフィの死因は, 呼吸筋低下による死亡が最も多いが, 心室細動や心室頻拍, 原因不明の突然死も約1/3ある. 今回, 筋緊張性ジストロフィの不整脈基質について検討を行った.<BR>症例1: 45歳, 男性. Mobitz II型房室ブロックにて入院. 心電図はI度房室ブロックを示し, 加算平均心電図では遅延電位陽性であった. 電気生理学的検査(EPS)では右室心尖部からの単回期外刺激で心室細動(VF)が誘発された.<BR>症例2: 49歳, 男性. 3年前に心房頻拍に対して心筋焼灼術施行した既往があった. I度およびMobitz II型房室ブロック精査のため入院した. 加算平均心電図では遅延電位陽性. EPSでは右室心尖部からの3連期外刺激でVFが誘発された.<BR>症例3: 49歳, 女性. 呼吸筋低下による人工呼吸管理中, 発作性2: 1房室ブロックを認め紹介となった. 心電図はI度房室ブロック, 完全右脚ブロックを示していた. Holter心電図では多形性の非持続性心室頻拍8連発を認めた.<BR>今回, 検討した3例はいずれも正常心機能で失神の既往歴はなかったが, II度以上の房室ブロックがあり, 1例では右脚ブロックも認めた. 遅延電位陽性でEPSを行った2例ではVFが誘発された. 筋緊張性ジストロフィでは房室ブロックの進行以外に心室性不整脈による突然死の可能性が報告されており, 1次予防として植込み型除細動器(ICD)植え込みを行った.

DOI： 10.11281/shinzo.43.S2_39

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掲載種別：研究論文（学術雑誌）  

DOI： 10.4020/jhrs.27.PJ3_053

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掲載種別：研究論文（学術雑誌）  

DOI： 10.4020/jhrs.27.OP36_4

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DOI： 10.4020/jhrs.27.CP1_07

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DOI： 10.4020/jhrs.27.OP18_2

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/humu.21605

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DOI： 10.4020/jhrs.27.PJ3_030

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 45-year-old man with dilated cardiomyopathy was admitted to our hospital due to congestive heart failure (CHF). Despite the optimal medical treatment, his condition had not improved because of severe left ventricular dysfunction. Because he experienced non-sustained ventricular tachycardia (VT), a biventricular implantable cardioverter-defibrillator (Bi-V ICD) was implanted for reduction of dyssynchrony and primary prevention of lethal tachyarrhythmia. After discharge, he developed CHF and was transported to our hospital by ambulance. In the ambulance, monomorphic sustained VT with 200 bpm suddenly occurred. The ICD detected it as fast VT and anti-tachycardia pacing (ATP) was delivered. After the ATP therapy, RR intervals of VT became irregular and prolonged. Ventricular fibrillation-like electrical activity was recorded by a far-field electrogram from the defibrillator, but the tachycardia cycle length exceeded 400 ms which is under the tachycardia detection rate. The device failed to deliver a shock and the patient had to be rescued with an external shock. This is a rare case of fast VT that degenerated into undetectable life-threatening tachyarrhythmia by ATP.

DOI： 10.1016/j.jccase.2010.06.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.hrthm.2010.09.008

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記述言語：英語   出版者・発行元：The Japanese Circulation Society  

Background: Mutations in SCN5A are reportedly linked to Brugada syndrome (BS), but recent observations suggest that they are not necessarily associated with ventricular fibrillation (VF) in BS patients. Therefore, the clinical importance of SCN5A mutations in BS patients was examined in the present study. Methods and Results: The 108 BS patients were examined for SCN5A mutations and various parameters were compared between patients with and without mutations. An implantable cardioverter defibrillator (ICD) was implanted in 49 patients and a predictor of appropriate ICD shock was investigated. The existence of a SCN5A mutation was not associated with initial VF episodes (21.7% vs 20.0%, P=0.373). In the secondary prevention group, appropriate shock-free survival rate was significantly lower in patients with spontaneous type 1 ECG than in those without (41.1% vs 85.7% at 2 years, P=0.014). The appropriate shock-free survival rate was also significantly lower in patients with SCN5A mutations than in those without (28.6% vs 83.3% at 1 year, P=0.040). Appropriate shock was more frequent in patients with SCN5A mutations than in those without (6.6±6.2 vs 1.7±3.0, P=0.007). Conclusions: SCN5A mutations are associated with early and frequent VF recurrence, but not with initial VF episodes. This is the first report on the genotype-phenotype interaction and clinical significance of this mutation. (Circ J 2010; 74: 2572-2578)<br>

DOI： 10.1253/circj.CJ-10-0445

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その他リンク： http://search.jamas.or.jp/link/ui/2011132854

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DOI： 10.1161/CIR.0b013e3181e037c1

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記述言語：英語  

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記述言語：英語  

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記述言語：日本語   出版者・発行元：(公財)日本心臓財団  

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1253/circj.CJ-10-0190

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/FJC.0b013e3181f03c2f

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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