907 results on '"Yasushi, Sakata"'
Search Results
2. Relationship of interleukin‐16 with different phenogroups in acute heart failure with preserved ejection fraction
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Shunsuke Tamaki, Yohei Sotomi, Yoshiyuki Nagai, Ryu Shutta, Daisaku Masuda, Nobuhiko Makino, Shizuya Yamashita, Masahiro Seo, Takahisa Yamada, Akito Nakagawa, Yoshio Yasumura, Yusuke Nakagawa, Masamichi Yano, Takaharu Hayashi, Shungo Hikoso, Daisaku Nakatani, Tomohito Ohtani, Yasushi Sakata, and the OCVC‐Heart Failure Investigators
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Acute decompensated heart failure ,Heart failure with preserved ejection fraction ,Inflammation ,Phenogroup ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims Interleukin‐16 (IL‐16) has been reported to mediate left ventricular myocardial fibrosis and stiffening in patients with heart failure with preserved ejection fraction (HFpEF). We sought to elucidate whether IL‐16 has a distinct impact on pathophysiology and prognosis across different subphenotypes of acute HFpEF. Methods and results We analysed 211 patients enrolled in a prospective multicentre registry of acute decompensated HFpEF for whom serum IL‐16 levels after stabilization were available (53% female, median age 81 [interquartile range 75–85] years). We divided this sub‐cohort into four phenogroups using our established clustering algorithm. The study endpoint was all‐cause death. Patients were subclassified into phenogroup 1 (‘rhythm trouble’ [n = 69]), phenogroup 2 (‘ventricular‐arterial uncoupling’ [n = 49]), phenogroup 3 (‘low output and systemic congestion’ [n = 41]), and phenogroup 4 (‘systemic failure’ [n = 52]). After a median follow‐up of 640 days, 38 patients had died. Among the four phenogroups, phenogroup 2 had the highest IL‐16 level. The IL‐16 level showed significant associations with indices of cardiac hypertrophy, diastolic dysfunction, and congestion only in phenogroup 2. Furthermore, the IL‐16 level had a significant predictive value for all‐cause death only in phenogroup 2 (C‐statistic 0.750, 95% confidence interval 0.606–0.863, P = 0.017), while there was no association between the IL‐16 level and the endpoint in the other phenogroups. Conclusions Our results indicated that the serum IL‐16 level had a significant association with indices that reflect the pathophysiology and prognosis of HFpEF in a specific phenogroup in acute HFpEF.
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- 2024
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3. Cardiac sympathetic nerve activity trends after renal denervation in heart failure with preserved ejection fraction
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Tatsuya Shiraki, Hiroya Mizuno, Takuya Kishi, Masanori Asakura, Hidetsugu Asanoi, Yoshio Yasumura, and Yasushi Sakata
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Heart failure ,Ultrasound renal denervation ,Estimated stressed blood volume ,Iodine‐123 metaiodobenzylguanidine ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract This case report describes the application of ultrasound renal denervation (uRDN) using the Paradise System in a patient with heart failure with preserved ejection fraction. Initially, the cardiac sympathetic nerve activity of the patient exhibited a late heart/mediastinum (H/M) ratio of 2.00 and a washout rate of 66.0% by cardiac iodine‐123 metaiodobenzylguanidine (123I‐MIBG) scintigraphy. Subsequently, the patient underwent transfemoral uRDN targeting the left, right upper, and right lower renal arteries. At the 6 month follow‐up, no significant change was observed in 123I‐MIBG findings; however, the estimated stressed blood volume (eSBV) decreased from 1722 to 1029 mL/70 kg. At 18 months, 123I‐MIBG findings improved, with the late H/M ratio reaching 2.76 and the washout rate decreasing to 43.1%. This case report highlights the potential of uRDN in reducing eSBV within 6 months and subsequently improving cardiac sympathetic nerve activity at the 18 month follow‐up.
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- 2024
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4. Low‐density lipoprotein cholesterol, erythrocyte, and platelet in heart failure with preserved ejection fraction
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Masamichi Yano, Masami Nishino, Shodai Kawanami, Kohei Ukita, Akito Kawamura, Koji Yasumoto, Masaki Tsuda, Naotaka Okamoto, Yasuharu Matsunaga‐Lee, Yasuyuki Egami, Takahisa Yamada, Yoshio Yasumura, Masahiro Seo, Takaharu Hayashi, Akito Nakagawa, Yusuke Nakagawa, Shunsuke Tamaki, Yohei Sotomi, Daisaku Nakatani, Shungo Hikoso, and Yasushi Sakata
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Erythrocyte ,Heart failure with preserved ejection fraction ,Low‐density lipoprotein cholesterol ,Platelet ,Prognosis ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims Low‐density lipoprotein cholesterol (LDL‐C), anaemia and low platelets have been associated with worse clinical outcomes in heart failure patients. We investigated the relationship between the combination of these three components and clinical outcome in patients with heart failure with preserved ejection fraction (HFpEF). Methods and results We examined the data of 1021 patients with HFpEF hospitalized with acute decompensated heart failure (HF) from the PURSUIT‐HFpEF registry, a prospective, multicenter observational study. The enrolled patients were classified into four groups by an LEP (LDL‐C, Erythrocyte, and Platelet) score of 0 to 3 points, with 1 point each for LDL‐C, erythrocyte and platelet values less than the cut‐off values as calculated by receiver operating characteristic curve analysis. The endpoint, a composite of all‐cause death and HF readmission, was evaluated among the four groups. Median follow‐up duration was 579 [300, 978] days. Risk of the composite endpoint significantly differed among the four groups (P
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- 2024
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5. Characteristic craniofacial defects associated with a novel USP9X truncation mutation
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Namiki Nagata, Hiroshi Kurosaka, Kotaro Higashi, Masaya Yamaguchi, Sayuri Yamamoto, Toshihiro Inubushi, Miho Nagata, Yasuki Ishihara, Ayumi Yonei, Yohei Miyashita, Yoshihiro Asano, Norio Sakai, Yasushi Sakata, Shigetada Kawabata, and Takashi Yamashiro
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Genetics ,QH426-470 ,Life ,QH501-531 - Abstract
Abstract Germline loss-of-function mutations in USP9X have been reported to cause a wide spectrum of congenital anomalies. Here, we report a Japanese girl with a novel heterozygous nonsense mutation in USP9X who exhibited intellectual disability with characteristic craniofacial abnormalities, including hypotelorism, brachycephaly, hypodontia, micrognathia, severe dental crowding, and an isolated submucous cleft palate. Our findings provide further evidence that disruptions in USP9X contribute to a broad range of congenital craniofacial abnormalities.
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- 2024
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6. Recurrent Pericardial Effusion Resulting From Right Ventricular Free Wall Injury Caused by Leadless Pacemaker Tines
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Takafumi Oka, MD, PhD, Kentaro Ozu, MD, Takayuki Sekihara, MD, Tetsuo Furukawa, MD, Shigeru Miyagawa, MD, PhD, and Yasushi Sakata, MD, PhD
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cardiac tamponade ,complication ,fixation ,leadless pacemaker ,tines ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
An 87-year-old man developed delayed cardiac tamponade 55 min after leadless pacemaker implantation and recurrent pericardial effusion 20 days later. Electrocardiogram-gated enhanced cardiac computed tomography revealed that the leadless pacemaker tines on the lateral side had penetrated the right ventricular free wall. He underwent off-pump hemostatic surgery.
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- 2024
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7. Uplift modeling to identify patients who require extensive catheter ablation procedures among patients with persistent atrial fibrillation
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Taiki Sato, Yohei Sotomi, Shungo Hikoso, Tetsuhisa Kitamura, Daisaku Nakatani, Katsuki Okada, Tomoharu Dohi, Akihiro Sunaga, Hirota Kida, Yuki Matsuoka, Nobuaki Tanaka, Tetsuya Watanabe, Nobuhiko Makino, Yasuyuki Egami, Takafumi Oka, Hitoshi Minamiguchi, Miwa Miyoshi, Masato Okada, Takashi Kanda, Yasuhiro Matsuda, Masato Kawasaki, Masaharu Masuda, Koichi Inoue, Yasushi Sakata, and the OCVC-Arrhythmia Investigators
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Medicine ,Science - Abstract
Abstract Identifying patients who would benefit from extensive catheter ablation along with pulmonary vein isolation (PVI) among those with persistent atrial fibrillation (AF) has been a subject of controversy. The objective of this study was to apply uplift modeling, a machine learning method for analyzing individual causal effect, to identify such patients in the EARNEST-PVI trial, a randomized trial in patients with persistent AF. We developed 16 uplift models using different machine learning algorithms, and determined that the best performing model was adaptive boosting using Qini coefficients. The optimal uplift score threshold was 0.0124. Among patients with an uplift score ≥ 0.0124, those who underwent extensive catheter ablation (PVI-plus) showed a significantly lower recurrence rate of AF compared to those who received only PVI (PVI-alone) (HR 0.40; 95% CI 0.19–0.84; P-value = 0.015). In contrast, among patients with an uplift score
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- 2024
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8. Quantitative analysis of fractionated electrogram area of left atrium during right atrial pacing as an indicator of left atrial electrical remodeling in patients with atrial fibrillation
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Takayuki Sekihara, Takafumi Oka, Kentaro Ozu, and Yasushi Sakata
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atrial fibrillation ,atrial remodeling ,atrial substrate ,conduction velocity ,ultrahigh‐resolution mapping ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background The clinical significance of left atrial local electrogram fractionation after restoration of sinus rhythm in patients with atrial fibrillation (AF) has not been elucidated. Methods We evaluated ultrahigh‐resolution maps of the left atrium (LA) during RA pacing acquired after pulmonary vein isolation in 40 patients with AF. The association between low‐voltage area (LVA,
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- 2024
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9. Empagliflozin cost‐effectiveness analysis in Japanese heart failure with mildly reduced and preserved ejection fraction
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Hiroyuki Tsutsui, Hiroyuki Sakamaki, Shin‐ichi Momomura, Yasushi Sakata, Yutaro Kotobuki, Stephan Linden, Koki Idehara, and Daisuke Nitta
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Heart failure with preserved ejection fraction ,Empagliflozin ,Japan ,Cost‐effectiveness analysis ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims Empagliflozin, a sodium‐glucose co‐transporter 2 inhibitor, was shown to be effective in patients with heart failure with preserved ejection fraction (HFpEF) in the EMPEROR‐Preserved trial. The present study aims to evaluate the cost‐effectiveness of empagliflozin among Japanese patients with HFpEF. Methods and results A Markov cohort model was developed to evaluate the cost‐effectiveness of empagliflozin added to standard of care (SoC) compared with SoC alone in patients with HFpEF from the perspective of the Japanese healthcare system and with a lifetime horizon. In addition to clinical events, the progression of disease severity was modelled based on the migration of Kansas City Cardiomyopathy Questionnaire‐Clinical Summary Scores (KCCQ‐CSS). Model inputs, including risk of clinical events, costs, and utilities/disutilities, were derived from EMPEROR‐Preserved trial data, a claims database and published literature. The generalizability of model results was investigated by applying various subgroups including age, body mass index (BMI), and region Asia, based on the subgroup analysis of EMPEROR‐Preserved data. In the base‐case analysis, empagliflozin yielded additional quality‐adjusted life years (QALYs; 0.11) with an incremental cost of $1408 per patient for Japanese patients with HFpEF. Incremental cost, mainly derived from drug acquisition cost ($1963 per patient), was largely offset by reduced cost in hospitalization for heart failure (HHF) and cardiovascular death (−$537 per patient and −$166 per patient, respectively). Treatment of empagliflozin provided incremental 0.11 QALYs and 0.08 life years compared with SoC alone. The incremental cost‐effectiveness ratio (ICER) was $12 772 (¥1 662 689)/QALY, which was below the Japanese willingness‐to‐pay (WTP) threshold of $38 408 (¥5 000 000)/QALY. The results were consistent across all the subgroups considered, and empagliflozin was dominant over SoC alone in the region Asia and BMI
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- 2024
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10. The WATCH-DM risk score estimates clinical outcomes in type 2 diabetic patients with heart failure with preserved ejection fraction
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Katsuomi Iwakura, Toshinari Onishi, Atsunori Okamura, Yasushi Koyama, Nobuaki Tanaka, Masato Okada, Kenshi Fujii, Masahiro Seo, Takahisa Yamada, Masamichi Yano, Takaharu Hayashi, Yoshio Yasumura, Yusuke Nakagawa, Shunsuke Tamaki, Akito Nakagawa, Yohei Sotomi, Shungo Hikoso, Daisaku Nakatani, Yasushi Sakata, and PURSUIT-HFpEF Investigators
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Medicine ,Science - Abstract
Abstract The coexistence of heart failure is frequent and associated with higher mortality in patients with type 2 diabetes (T2DM), and its management is a critical issue. The WATCH-DM risk score is a tool to predict heart failure in patients with type 2 diabetes mellitus (T2DM). We investigated whether it could estimate outcomes in T2DM patients with heart failure with preserved ejection fraction (HFpEF). The WATCH-DM risk score was calculated in 418 patients with T2DM hospitalized for HFpEF (male 49.5%, age 80 ± 9 years, HbA1c 6.8 ± 1.0%), and they were divided into the “average or lower” (≤ 10 points), “high” (11–13 points) and “very high” (≥ 14 points) risk groups. We followed patients to observe all-cause death for 386 days (median). We compared the area under the curve (AUC) of the WATCH-DM score for predicting 1-year mortality with that of the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score and of the Barcelona Bio-Heart Failure Risk (BCN Bio-HF). Among the study patients, 108 patients (25.8%) had average or lower risk scores, 147 patients (35.2%) had high risk scores, and 163 patients (39.0%) had very high risk scores. The Cox proportional hazard model selected the WATCH-DM score as an independent predictor of all-cause death (HR per unit 1.10, 95% CI 1.03 to 1.19), and the “average or lower” risk group had lower mortality than the other groups (p = 0.047 by log-rank test). The AUC of the WATCH-DM for 1-year mortality was 0.64 (95% CI 0.45 to 0.74), which was not different from that of the MAGGIC score (0.72, 95% CI 0.63 to 0.80, p = 0.08) or that of BCN Bio-HF (0.70, 0.61 to 0.80, p = 0.25). The WATCH-DM risk score can estimate prognosis in T2DM patients with HFpEF and can identify patients at higher risk of mortality.
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- 2024
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11. SARS-CoV-2 spike receptor-binding domain is internalized and promotes protein ISGylation in human induced pluripotent stem cell-derived cardiomyocytes
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Shota Okuno, Shuichiro Higo, Takumi Kondo, Mikio Shiba, Satoshi Kameda, Hiroyuki Inoue, Tomoka Tabata, Shou Ogawa, Yu Morishita, Congcong Sun, Saki Ishino, Tomoyuki Honda, Shigeru Miyagawa, and Yasushi Sakata
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Medicine ,Science - Abstract
Abstract Although an increased risk of myocarditis has been observed after vaccination with mRNA encoding severe acute respiratory syndrome coronavirus 2 spike protein, its underlying mechanism has not been elucidated. This study investigated the direct effects of spike receptor-binding domain (S-RBD) on human cardiomyocytes differentiated from induced pluripotent stem cells (iPSC-CMs). Immunostaining experiments using ACE2 wild-type (WT) and knockout (KO) iPSC-CMs treated with purified S-RBD demonstrated that S-RBD was bound to ACE2 and internalized into the subcellular space in the iPSC-CMs, depending on ACE2. Immunostaining combined with live cell imaging using a recombinant S-RBD fused to the superfolder GFP (S-RBD-sfGFP) demonstrated that S-RBD was bound to the cell membrane, co-localized with RAB5A, and then delivered from the endosomes to the lysosomes in iPSC-CMs. Quantitative PCR array analysis followed by single cell RNA sequence analysis clarified that S-RBD-sfGFP treatment significantly upregulated the NF-kβ pathway-related gene (CXCL1) in the differentiated non-cardiomyocytes, while upregulated interferon (IFN)-responsive genes (IFI6, ISG15, and IFITM3) in the matured cardiomyocytes. S-RBD-sfGFP treatment promoted protein ISGylation, an ISG15-mediated post-translational modification in ACE2-WT-iPSC-CMs, which was suppressed in ACE2-KO-iPSC-CMs. Our experimental study demonstrates that S-RBD is internalized through the endolysosomal pathway, which upregulates IFN-responsive genes and promotes ISGylation in the iPSC-CMs.
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- 2023
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12. Human leukocyte antigen-DQ risk heterodimeric haplotypes of left ventricular dysfunction in cardiac sarcoidosis: an autoimmune view of its role
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Hironori Yamamoto, Yohei Miyashita, Hitoshi Minamiguchi, Kazuyoshi Hosomichi, Shohei Yoshida, Hidetaka Kioka, Haruki Shinomiya, Haruno Nagata, Kenji Onoue, Masato Kawasaki, Yuki Kuramoto, Akihiro Nomura, Yuichiro Toma, Tetsuya Watanabe, Takahisa Yamada, Yasuki Ishihara, Miho Nagata, Hisakazu Kato, Hideyuki Hakui, Yoshihiko Saito, Yoshihiro Asano, and Yasushi Sakata
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Medicine ,Science - Abstract
Abstract Cardiac sarcoidosis (CS) is the scarring of heart muscles by autoimmunity, leading to heart abnormalities and patients with sarcoidosis with cardiac involvements have poor prognoses. Due to the small number of patients, it is difficult to stratify all patients of CS by human leukocyte antigen (HLA) analysis. We focused on the structure of antigen-recognizing pockets in heterodimeric HLA-class II, in addition to DNA sequences, and extracted high-affinity combinations of antigenic epitopes from candidate autoantigen proteins and HLA. Four HLA heterodimer-haplotypes (DQA1*05:03/05:05/05:06/05:08-DQB1*03:01) were identified in 10 of 68 cases. Nine of the 10 patients had low left ventricular ejection fraction (
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- 2023
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13. Lower doses of carvedilol in Japanese heart failure patients with reduced ejection fraction could show the potential to be non-inferior to higher doses in US patients: An international collaborative observational study.
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Makiko Maeda, Douglas Humber, Eisuke Hida, Tomohito Ohtani, Guannan Wang, Tong Wu, Shiori Takeda, Jacinta N Situ, Jun Hayashi, Shinpei Nonen, Toshihiro Takeda, Hiroshi Okamoto, Masatsugu Hori, Yasushi Sakata, Yasushi Fujio, and Shirley M Tsunoda
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Medicine ,Science - Abstract
The Japanese national guidelines recommend significantly lower doses of carvedilol for heart failure with reduced ejection fraction (HFrEF) management than the US guidelines. Using real-world data, we determined whether initial and target doses of carvedilol in Japanese patients (JPNs) differ from those in US patients (USPs), especially in Asian Americans (ASA) and Caucasians (CA), and investigated differences in outcomes. We collected data from the electronic medical records, including demographics, carvedilol dosing, tolerability, cardiac functional indicators like EF, cardiovascular events including all-cause deaths, and laboratory values from the University of California, San Diego Health and Osaka University. JPNs had significantly lower doses (mg/day) of carvedilol initiation (66 USPs composed of 38 CAs and 28 ASAs, 17.1±16.2; 93 JPNs, 4.3±4.2, p
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- 2024
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14. Sleep apnea severity in patients undergoing atrial fibrillation ablation: Home sleep apnea‐test and polysomnography comparison
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Nobuaki Tanaka, Masato Okada, Koji Tanaka, Toshinari Onishi, Yuko Hirao, Shinichi Harada, Masatsugu Kawahira, Yasushi Koyama, Kenshi Fujii, Heitaro Watanabe, Atsunori Okamura, Yasushi Sakata, and Katsuomi Iwakura
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atrial fibrillation ,catheter ablation ,home sleep apnea test ,polysomnography ,sleep apnea ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Sleep apnea (SA) is highly prevalent and should be treated in patients referred for catheter ablation (CA) of atrial fibrillation (AF). Watch‐type peripheral arterial tonometry (WP) for home SA testing has demonstrated a high correlation of the apnea‐hypopnea index (AHI) with Polysomnography (PSG), but the evidence of its accuracy in AF patients is not adequate. Methods This study was conducted under a retrospective, single‐center, observational design. We included 464 consecutive AF patients (age 65 ± 11 years, 76.5% male, 45.0% paroxysmal‐AF) who received both WP and PSG during the periprocedural period of the CA. We compared the AHI using the WP (WP‐AHI) to that using PSG (PSG‐AHI). Results The WP‐AHI was 25.9 ± 12.7 and PSG‐AHI 31.4 ± 18.9 (r = .48). Among 325 patients with a WP‐AHI
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- 2023
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15. P2Y12 inhibitor monotherapy after complex percutaneous coronary intervention: a systematic review and meta-analysis of randomized clinical trials
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Yohei Sotomi, Yuki Matsuoka, Shungo Hikoso, Daisaku Nakatani, Katsuki Okada, Tomoharu Dohi, Hirota Kida, Bolrathanak Oeun, Akihiro Sunaga, Taiki Sato, Tetsuhisa Kitamura, and Yasushi Sakata
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Medicine ,Science - Abstract
Abstract It remains unknown whether the recent trend of short dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy can simply be applied to patients undergoing complex percutaneous coronary intervention (PCI). We performed a systematic review and meta-analysis to evaluate P2Y12 inhibitor monotherapy vs. conventional DAPT in patients undergoing complex PCI and non-complex PCI (PROSPERO: CRD42022335723). Primary endpoint was the 1-year Net Adverse Clinical Event (NACE). Among 5,323 screened studies, six randomized trials fulfilled the eligibility criteria. A total of 10,588 complex PCI patients (5,269 vs. 5,319 patients) and 25,618 non-complex PCI patients (12,820 vs 12,798 patients) were randomly assigned to P2Y12 inhibitor monotherapy vs. conventional DAPT. In complex PCI patients, P2Y12 inhibitor monotherapy was associated with a lower risk of NACE than conventional DAPT [Odds ratio (OR) 0.76, 95% confidence interval (CI) 0.63–0.91, P = 0.003], whereas in non-complex PCI patients, P2Y12 inhibitor monotherapy was associated with a trend toward lowering the risk of NACE (OR 0.86, 95% CI 0.72–1.02, P = 0.09). This meta-analysis across randomized trials demonstrated that a strategy of short DAPT followed by P2Y12 inhibitor monotherapy reduces the risk of 1-year NACE in patients undergoing complex PCI.
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- 2023
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16. Lysophosphatidylserine induces necrosis in pressure overloaded male mouse hearts via G protein coupled receptor 34
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Ryuta Sugihara, Manabu Taneike, Tomokazu Murakawa, Takahito Tamai, Hiromichi Ueda, Rika Kitazume-Taneike, Takafumi Oka, Yasuhiro Akazawa, Hiroki Nishida, Kentaro Mine, Ayana Hioki, Jumpei Omi, Shigemiki Omiya, Junken Aoki, Kazutaka Ikeda, Kazuhiko Nishida, Makoto Arita, Osamu Yamaguchi, Yasushi Sakata, and Kinya Otsu
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Science - Abstract
Abstract Heart failure is a leading cause of mortality in developed countries. Cell death is a key player in the development of heart failure. Calcium-independent phospholipase A2β (iPLA2β) produces lipid mediators by catalyzing lipids and induces nuclear shrinkage in caspase-independent cell death. Here, we show that lysophosphatidylserine generated by iPLA2β induces necrotic cardiomyocyte death, as well as contractile dysfunction mediated through its receptor, G protein-coupled receptor 34 (GPR34). Cardiomyocyte-specific iPLA2β-deficient male mice were subjected to pressure overload. While control mice showed left ventricular systolic dysfunction with necrotic cardiomyocyte death, iPLA2β-deficient mice preserved cardiac function. Lipidomic analysis revealed a reduction of 18:0 lysophosphatidylserine in iPLA2β-deficient hearts. Knockdown of Gpr34 attenuated 18:0 lysophosphatidylserine-induced necrosis in neonatal male rat cardiomyocytes, while the ablation of Gpr34 in male mice reduced the development of pressure overload-induced cardiac remodeling. Thus, the iPLA2β—lysophosphatidylserine—GPR34—necrosis signaling axis plays a detrimental role in the heart in response to pressure overload.
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- 2023
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17. Not brushing teeth at night may increase the risk of cardiovascular disease
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Emiko Tanaka Isomura, Shinichiro Suna, Hiroyuki Kurakami, Shungo Hikoso, Toshihiro Uchihashi, Yusuke Yokota, Yasushi Sakata, and Susumu Tanaka
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Medicine ,Science - Abstract
Abstract In this study, we investigated whether toothbrushing timing affects cardiovascular disease risk. We enrolled 1675 patients aged ≥ 20 years who were hospitalized for surgery, examination, or medical treatment. The participants were categorized as follows based on toothbrushing: Group MN (brushing teeth after waking up and at night, n = 409), Group Night (brushing teeth at night but not upon waking up, n = 751), Group M (brushing teeth after waking up but not at night, n = 164), and Group None (not brushing teeth at all, n = 259). The participants’ age, sex, smoking history, and follow-up results were evaluated. Group M had four times as many men as women. Multivariate analysis of cardiovascular events showed significantly higher survival estimates in Group MN (P = 0.021) and Group Night (P = 0.004) than in Group None. Kaplan–Meier analysis of subgroups based on smoking status revealed that smokers in Group None had significantly worse prognosis for cardiovascular onset events than smokers in other groups; non-smokers in Groups None and M showed significantly worse prognosis on hospitalization. Our findings are limited to cardiovascular diseases and cannot be generalized to healthy populations. However, we suggest that brushing teeth at night is important for lowering cardiovascular disease risk.
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- 2023
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18. Left atrial anterolateral linear ablation for biatrial tachycardia via Bachmann's bundle, interatrial septum, and left atrial anterior wall under mitral isthmus block
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Takayuki Sekihara, Takafumi Oka, Kentaro Ozu, and Yasushi Sakata
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Bachmann's bundle ,biatrial tachycardia ,ultra‐high‐resolution mapping ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2023
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19. Application of Magnetic Resonance Strain Analysis Using Feature Tracking in a Myocardial Infarction Model
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Ryutaro Onishi, Junpei Ueda, Seiko Ide, Masahiro Koseki, Yasushi Sakata, and Shigeyoshi Saito
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MR strain analysis ,7T-MRI ,myocardial infarction model ,Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
This study validates the usefulness of myocardial strain analysis with cardiac cine magnetic resonance imaging (MRI) by evaluating the changes in the cardiac function and myocardial strain values longitudinally in a myocardial disease model. Six eight-week-old male Wistar rats were used as a model of myocardial infarction (MI). Cine images were taken in the short axis, two-chamber view longitudinal axis, and four-chamber view longitudinal axis directions in rats 3 and 9 days after MI and in control rats, with preclinical 7-T MRI. The control images and the images on days 3 and 9 were evaluated by measuring the ventricular ejection fraction (EF) and the strain values in the circumferential (CS), radial (RS), and longitudinal directions (LS). The CS decreased significantly 3 days after MI, but there was no difference between the images on days 3 and 9. The two-chamber view LS was −9.7 ± 2.1% at 3 days and −13.9 ± 1.4% at 9 days after MI. The four-chamber view LS was −9.9 ± 1.5% at 3 days and −11.9 ± 1.3% at 9 days after MI. Both the two- and four-chamber LS values were significantly decreased 3 days after MI. Myocardial strain analysis is, therefore, useful for assessing the pathophysiology of MI.
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- 2023
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20. The clinical relevance of quality of life in heart failure patients with preserved ejection fraction
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Masahiro Seo, Tetsuya Watanabe, Takahisa Yamada, Masamichi Yano, Takaharu Hayashi, Akito Nakagawa, Yusuke Nakagawa, Shunsuke Tamaki, Yoshio Yasumura, Yohei Sotomi, Shungo Hikoso, Daisaku Nakatani, Masatake Fukunami, and Yasushi Sakata
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Quality of life ,EQ‐5D ,HFpEF ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims Patient reported outcomes (PROs) are gradually being incorporated into daily practice to assess individual health‐related quality of life (QOL). However, despite accumulating evidence of the prognostic utility of heart failure (HF)‐specific QOL indices, evidence on the generic QOL score is scarce, especially in patients with HF with preserved ejection fraction (HFpEF). Methods and results Patient data were extracted from the Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study. EuroQol 5 dimensions 5‐level (EQ‐5D‐5L) data were obtained at discharge to evaluate patients' health‐related QOL. The study population (n = 864) was divided into tertiles based on their EQ‐5D‐5L index as follows: low EQ‐5D‐5L 0.038–0.664 (n = 287), middle EQ‐5D‐5L 0.665–0.867 (n = 293), and high EQ‐5D‐5L 0.871–1.000 (n = 284). A total of 206 patients died over a mean follow‐up period of 2.0 ± 1.2 years. Kaplan–Meier analysis revealed that the risk of mortality increased with the tertile of the EQ‐5D‐5L index (34% vs. 23% vs. 14%, P
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- 2023
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21. GFRA2 Identifies Cardiac Progenitors and Mediates Cardiomyocyte Differentiation in a RET-Independent Signaling Pathway
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Hidekazu Ishida, Rie Saba, Ioannis Kokkinopoulos, Masakazu Hashimoto, Osamu Yamaguchi, Sonja Nowotschin, Manabu Shiraishi, Prashant Ruchaya, Duncan Miller, Stephen Harmer, Ariel Poliandri, Shigetoyo Kogaki, Yasushi Sakata, Leo Dunkel, Andrew Tinker, Anna-Katerina Hadjantonakis, Yoshiki Sawa, Hiroshi Sasaki, Keiichi Ozono, Ken Suzuki, and Kenta Yashiro
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Biology (General) ,QH301-705.5 - Published
- 2023
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22. Successful antihypertensive treatment using sacubitril/valsartan alone in a patient with obstructive sleep apnoea syndrome
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Ryuta Sugihara, Yuusaku Sugihara, Itsuko Sugihara, and Yasushi Sakata
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síndrome de apnea obstructiva del sueño ,hipertensión ,sacubitril/valsartán ,Medicine (General) ,R5-920 - Abstract
Obstructive sleep apnoea syndrome (O-SAS) induces excessive activity of the sympathetic nervous system, resulting in secondary hypertension. Although continuous positive airway pressure (CPAP) is the first-line therapy for O-SAS, poor adherence to CPAP induces uncontrollable resistant hypertension. We present a case of O-SAS-related hypertension successfully treated with sacubitril/valsartan alone. Polysomnography before treatment showed a markedly increased apnoea-hypopnoea index (44.8/hour). While receiving treatment with CPAP and azilsartan, his in-office blood pressure remained within the acceptable range (120–130/80–85 mmHg). However, his blood pressure increased again after quitting CPAP. Subsequently, we switched to sacubitril/valsartan alone and succeeded in improving his blood pressure from 145/95 to 120/80 mmHg. Furthermore, sacubitril/valsartan improved sleep quality in terms of blood pressure (from non-dipper type to dipper type) and apnoea-hypopnoea index (38.3/hour). This case indicates that sacubitril/valsartan has great potential for antihypertensive effects in patients with severe O-SAS, even without CPAP. Resumen: El síndrome de apnea obstructiva del sueño (SAOS) induce actividad excesiva del sistema nervioso simpático, ocasionando hipertensión secundaria. Aunque la presión positiva continua en vía respiratoria (CPAP) es el tratamiento inicial para SAOS, mala adherencia a CPAP provoca hipertensión resistente incontrolable. Presentamos un caso de hipertensión relacionada con SAOS tratada exitosamente solo con sacubitril/valsartán. La polisomnografía pre-tratamiento mostró un índice de apnea-hipopnea notablemente aumentado (44,8/hora). Tratando con CPAP y azilsartán, su presión arterial en consultorio permaneció en rango aceptable (120-130/80-85 mmHg). Pero, su presión arterial volvió a aumentar tras dejar la CPAP. Posteriormente, cambiamos a solo sacubitril/valsartán, consiguiendo mejorar su presión arterial (de 145/95 a 120/80 mmHg). Además, sacubitril/valsartán mejoró la calidad de sueño durante el sueño en términos de presión arterial (tipo no dipper a tipo dipper) y del índice de apnea-hipopnea (38,3/hora). Este caso demuestra que sacubitril/valsartán tiene un gran potencial de efectos antihipertensivos en pacientes con SAOS grave, incluso sin CPAP.
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- 2023
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23. Myocardial fat accumulation is associated with cardiac dysfunction in patients with type 2 diabetes, especially in elderly or female patients: a retrospective observational study
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Risa Kashiwagi-Takayama, Junji Kozawa, Yoshiya Hosokawa, Sarasa Kato, Satoshi Kawata, Harutoshi Ozawa, Ryohei Mineo, Chisaki Ishibashi, Megu Y. Baden, Ryuya Iwamoto, Kenji Saisho, Yukari Fujita, Sachiko Tamba, Takuya Sugiyama, Hitoshi Nishizawa, Norikazu Maeda, Koji Yamamoto, Masahiro Higashi, Yuya Yamada, Yasushi Sakata, Yuji Matsuzawa, and Iichiro Shimomura
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Ectopic fat ,Type 2 diabetes ,Myocardium ,Myocardial function ,Visceral obesity ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background Ectopic fat is fat that accumulates in or around specific organs or compartments of the body including myocardium. The clinical features of type 2 diabetes patients with high fat accumulation in the myocardium remain unknown. Moreover, little is known about the influence of myocardial fat accumulation in type 2 diabetes on coronary artery disease and cardiac dysfunction. We aimed to clarify the clinical features, including cardiac functions, of type 2 diabetes patients with myocardial fat accumulation. Methods We retrospectively enrolled type 2 diabetes patients who underwent ECG-gated coronary computed tomography angiography (CCTA) and abdominal computed tomography (CT) scan examinations within 1 year of CCTA from January 2000 to March 2021. High fat accumulation in the myocardium was defined as the low mean myocardial CT value of three regions of interest, and the associations between CT values and clinical characteristics or cardiac functions were assessed. Results In total, 124 patients were enrolled (72 males and 52 females). The mean age was 66.6 years, the mean BMI was 26.2 kg/m2, the mean ejection fraction (EF) was 67.6%, and the mean myocardial CT value was 47.7 Hounsfield unit. A significant positive correlation was found between myocardial CT value and EF (r = 0.3644, p = 0.0004). The multiple regression analyses also showed that myocardial CT value was independently associated with EF (estimate, 0.304; 95% confidence interval (CI) 0.092 to 0.517; p = 0.0056). Myocardial CT value showed significant negative correlations with BMI, visceral fat area and subcutaneous fat area (r = − 0.1923, − 0.2654, and -0.3569, respectively, p
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- 2023
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24. Safety confirmation of induced pluripotent stem cell-derived cardiomyocyte patch transplantation for ischemic cardiomyopathy: first three case reports
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Takuji Kawamura, Yoshito Ito, Emiko Ito, Maki Takeda, Tsubasa Mikami, Takura Taguchi, Noriko Mochizuki-Oda, Masao Sasai, Tomomi Shimamoto, Yukako Nitta, Daisuke Yoshioka, Masashi Kawamura, Ai Kawamura, Yusuke Misumi, Yasushi Sakata, Yoshiki Sawa, and Shigeru Miyagawa
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cardiomyocyte patch transplantation ,iPS cells ,myocardial regenerative medicine ,heart failure ,immune response ,HLA antibodies ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
IntroductionWith the expected increase in patients with heart failure and ischemic 15 cardiomyopathy, the development of myocardial regenerative medicine using cell transplantation as a novel treatment method is progressing. This first-in-human clinical trial aimed to confirm the safety of cardiomyocyte patch transplantation derived from allogeneic induced pluripotent stem (iPS) cells based on the results of several preclinical studies.Study designThe inclusion criteria were left ventricular ejection fraction of 35% or less; heart failure symptoms of New York Heart Association class III or higher despite existing therapies such as revascularization; and a 1-year observation period that included a 3-month immunosuppressive drug administration period after transplantation of iPS cell-derived cardiomyocyte patches to evaluate adverse events, cardiac function, myocardial blood flow, heart failure symptoms, and immune response.ResultsIn the first three cases of this trial, no transplanted cell-related adverse events were observed during the 1-year observation period, and improvement in heart failure symptoms was observed. In addition, improvements in left ventricular contractility and myocardial blood flow were observed in two of the three patients. Regarding immune response, an increase in transplant cell-specific antibody titer was observed in all three patients after immunosuppressive drug administration. In one patient with poor improvement in cardiac function and myocardial blood flow, an increase in antibody titer against HLA-DQ was observed even before cell transplantation.ConclusionsOur case findings demonstrate that the transplantation of iPS cell-derived cardiomyocyte patches for ischemic cardiomyopathy can be safely performed; however, further investigation of the therapeutic effect and its relationship with an immune response is needed by accumulating the number of patients through continued clinical trials.
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- 2023
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25. Long‐Term Impact of Additional Ablation After Pulmonary Vein Isolation: Results From EARNEST‐PVI Trial
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Masaharu Masuda, Koichi Inoue, Nobuaki Tanaka, Tetsuya Watanabe, Nobuhiko Makino, Yasuyuki Egami, Takafumi Oka, Hitoshi Minamiguchi, Miwa Miyoshi, Masato Okada, Takashi Kanda, Toshiaki Mano, Yasuhiro Matsuda, Hiroyuki Uematsu, Takashige Sakio, Masato Kawasaki, Akihiro Sunaga, Yohei Sotomi, Tomoharu Dohi, Daisaku Nakatani, Shungo Hikoso, and Yasushi Sakata
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left atrial ablation ,linear ablation ,persistent atrial fibrillation ,recurrence ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background An optimal strategy for left atrial ablation in addition to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF) has not been determined. Methods and Results We conducted an extended follow‐up of the multicenter randomized controlled EARNEST‐PVI (Efficacy of Pulmonary Vein Isolation Alone in Patients With Persistent Atrial Fibrillation) trial, which compared 12‐month rhythm outcomes in patients with persistent AF between patients randomized to a PVI‐alone strategy (n=248) or PVI‐plus strategy (n=248; PVI followed by left atrial additional ablation, including linear ablation or ablation targeting areas with complex fractionated electrograms). The present study extended the follow‐up period to 3 years after enrollment. Outcomes were compared not only between randomly allocated groups but also between on‐treatment groups categorized by actually created ablation lesions. Recurrence rate of AF or atrial tachycardia (AT) was lower in the randomly allocated to PVI‐plus group than the PVI‐alone group (29.0% versus 37.5%, P=0.036). On‐treatment analysis revealed that patients with PVI+linear ablation (n=205) demonstrated a lower AF/AT recurrence rate than those with PVI only (26.3% versus 37.8%, P=0.007). In contrast, patients with PVI+complex fractionated electrograms ablation (n=37) had an AF/AT recurrence rate comparable to that of patients with PVI only (40.5% versus 37.8%, P=0.76). At second ablation in 126 patients with AF/AT recurrence, ATs excluding common atrial flutter were more frequent in patients with PVI+linear ablation than in those with PVI only (32.6% versus 5.7%, P
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- 2023
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26. First Case Report of Electromagnetic Interference Between Percutaneous Ventricular Assist Device and Implantable Cardioverter-Defibrillator
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Kosuke Takahari, MD, Takafumi Oka, MD, PhD, Takayuki Sekihara, MD, Kentaro Ozu, MD, Yasuhiro Akazawa, MD, PhD, Daisuke Nakamura, MD, Isamu Mizote, MD, PhD, Tomohito Ohtani, MD, PhD, Shungo Hikoso, MD, PhD, and Yasushi Sakata, MD, PhD
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electromagnetic interference ,ICD ,Impella ,telemetry ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Electromagnetic interference (EMI) between implantable left ventricular assist devices and cardiac implantable electronic devices has been observed. We demonstrated the first case of EMI between a percutaneous ventricular assist device and an implantable cardioverter-defibrillator, validated by an extra vivo simulation test. EMI might depend on the distance between devices. (Level of Difficulty: Advanced.)
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- 2023
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27. Reliability of transient elastography as a noninvasive method for estimating central venous pressure in adult patients after a Fontan procedure
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Misugi Emi, Fusako Sera, Yasumasa Tsukamoto, Yasuhiro Akazawa, Kei Nakamoto, Ryo Ishii, Hidekazu Ishida, Jun Narita, Masaki Taira, Tomohito Ohtani, Shungo Hikoso, Shigeru Miyagawa, and Yasushi Sakata
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Adult ,Fontan procedure ,Central venous pressure ,Transient elastography ,Liver stiffness ,Liver cirrhosis ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background: In adult patients, after a Fontan procedure, high central venous pressure (CVP) is a hemodynamic risk factor associated with poor prognosis. High liver stiffness (LS) on transient elastography (TE) is associated with high CVP in patients with heart failure without liver disease. Here, we investigated whether LS assessment using TE is a reliable method to noninvasively evaluate CVP in adult patients after a Fontan procedure, who can present varying degrees of liver fibrosis as a complication. Methods: We measured LS using TE and CVP by cardiac catheterization in 24 adult patients who had undergone a Fontan procedure. The estimated CVP was calculated using the previously reported formula: −5.8 + 6.7 × ln[LS]. We examined the correlation between LS and CVP, and degree of agreement between the estimated and measured CVPs. Patients were divided into two groups, with or without suspected liver cirrhosis, based on abdominal imaging studies. Results: The median patient age was 35 years (interquartile range 25, 39). Overall, there was a strong correlation between LS and CVP (ρ = 0.83, p
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- 2023
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28. Evaluation of the efficacy and safety of an integrated telerehabilitation platform for home-based cardiac REHABilitation in patients with heart failure (E-REHAB): protocol for a randomised controlled trial
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Ryosuke Murai, Keisuke Kida, Hiroshi Suzuki, Yasushi Sakata, Takayuki Ise, Shin-ichiro Miura, HIROKAZU KONDO, Yuichi Tamura, Misato Chimura, Tatsunori Taniguchi, Kensuke Takabayashi, Shinji Koba, Hiroyuki Miura, Emi Maekawa, Koki Matsuo, Wataru Fujimoto, Shunsuke Imai, Hideki Origuchi, Akiko Goda, Ryotaro Saita, and Atsushi Kikuchi
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Medicine - Abstract
Introduction Cardiac rehabilitation (CR) is strongly recommended as a medical treatment to improve the prognosis and quality of life of patients with heart failure (HF); however, participation rates in CR are low compared with other evidence-based treatments. One reason for this is the geographical distance between patients’ homes and hospitals. To address this issue, we developed an integrated telerehabilitation platform, RH-01, for home-based CR. We hypothesised that using the RH-01 platform for home-based CR would demonstrate non-inferiority compared with traditional centre-based CR.Methods and analysis The E-REHAB trial aims to evaluate the efficacy and safety of RH-01 for home-based CR compared with traditional centre-based CR for patients with HF. This clinical trial will be conducted under a prospective, randomised, controlled and non-inferiority design with a primary focus on HF patients. Further, to assess the generalisability of the results in HF to other cardiovascular disease (CVD), the study will also include patients with other CVDs. The trial will enrol 108 patients with HF and 20 patients with other CVD. Eligible HF patients will be randomly assigned to either traditional centre-based CR or home-based CR in a 1:1 fashion. Patients with other CVDs will not be randomised, as safety assessment will be the primary focus. The intervention group will receive a 12-week programme conducted two or three times per week consisting of a remotely supervised home-based CR programme using RH-01, while the control group will receive a traditional centre-based CR programme. The primary endpoint of this trial is change in 6 min walk distance.Ethics and dissemination The conduct of the study has been approved by an institutional review board at each participating site, and all patients will provide written informed consent before entry. The report of the study will be disseminated via scientific fora, including peer-reviewed publications and presentations at conferences.Trial registration number jRCT:2052200064.
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- 2023
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29. Nifekalant unmasked residual gap of superior vena cava isolation by suppressing immediate recurrence of intra‐superior vena cava fibrillation
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Takayuki Sekihara, Takafumi Oka, Tomoaki Nakano, Kentaro Ozu, and Yasushi Sakata
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atrial fibrillation ,immediate recurrence of atrial fibrillation ,Nifekalant ,superior vena cava isolation ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2022
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30. Preoperative hypomagnesemia as a possible predictive factor for postoperative increase of transvalvular pressure gradient in hemodialysis patients treated with transcatheter aortic valve implantation
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Satoshi Masuyama, Masayuki Mizui, Koichi Maeda, Kazuo Shimamura, Yusuke Sakaguchi, Masashi Morita, Toru Kuratani, Isamu Mizote, Daisuke Nakamura, Yasushi Sakata, Yoshiki Sawa, Shigeru Miyagawa, and Yoshitaka Isaka
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Magnesium ,TAVI ,valve dysfunction ,hemodialysis ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Background Patients undergoing maintenance hemodialysis (HD) with severe aortic stenosis are at a high risk for bioprosthetic valve dysfunction after transcatheter aortic valve implantation (TAVI). Currently, preoperative factors that predict the occurrence of valve dysfunction after TAVI on HD patients remain to be elucidated. The aim of this study is to analyze the association between preoperative clinical factors and valve stenosis after TAVI on HD patients.Methods Twenty-four of HD patients who underwent TAVI at our institution between April 2012 and January 2016 were analyzed. The mean aortic transvalvular pressure gradient (MPG) and effective orifice area index (EOAi) were assessed by serial echocardiography. Associations between preoperative clinical factors and time-series changes in MPG were examined using mixed-effects linear regression model for repeated measures.Results Three patients developed severe structural valve deterioration with calcific valve stenosis requiring reoperation. A multivariate linear mixed-effects model showed that lower serum magnesium (sMg) levels were associated with the increase of MPG after TAVI (beta-coefficient = 0.019, p = 0.03). No correlation was observed with serum calcium, phosphorus, or intact parathyroid hormone. Time-series changes of MPG and EOAi had significant difference between lower and higher sMg group. All 3 of the patients who underwent reoperation showed lower preoperative sMgs.Conclusion Among bone-mineral metabolism markers, preoperative hypomagnesemia was associated with the increase of MPG after TAVI, suggesting that hypomagnesemia could predict post-TAVI valve dysfunction in HD patients. Further studies with larger sample sizes are warranted.
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- 2022
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31. Right Ventricular Dimension for Heart Failure With Preserved Ejection Fraction Involving Right Ventricular-Vascular Uncoupling
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Akito Nakagawa, MD, PhD, Yoshio Yasumura, MD, PhD, Chikako Yoshida, MD, PhD, Takahiro Okumura, MD, PhD, Jun Tateishi, MD, PhD, Masahiro Seo, MD, Masamichi Yano, MD, PhD, Takaharu Hayashi, MD, PhD, Yusuke Nakagawa, MD, PhD, Shunsuke Tamaki, MD, PhD, Takahisa Yamada, MD, PhD, Yohei Sotomi, MD, PhD, Daisaku Nakatani, MD, PhD, Shungo Hikoso, MD, PhD, and Yasushi Sakata, MD, PhD
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background: Right ventricular (RV) to pulmonary artery (PA) uncoupling is known to be important for the prognosis of not only heart failure (HF) with reduced ejection fraction but also HF with preserved ejection fraction (HFpEF). We further investigated key factors in the poor prognosis for HFpEF patients with RV-PA uncoupling. Methods: We studied 817 patients with HFpEF who were discharged alive in a multicentred cohort using post hoc analyses, with a primary endpoint of cardiac mortality or HF readmission. A total of 288 RV-PA uncoupled patients were observed, namely those with a tricuspid annular plane systolic excursion (TAPSE)/PA systolic pressure (PASP) ratio < 0.46 mm/mm Hg. Results: Among the RV-PA uncoupled patients, 101 adverse outcomes occurred over a median of 340 days. Echocardiographic RV dimension (RVD) was significantly important for prognosis in both univariable and multivariable Cox regression testing (hazard ratio 1.044, 95% confidence interval 1.014-1.074, P = 0.0042, and hazard ratio 1.036, 95% confidence interval 1.001-1.072, P = 0.0438, respectively) considered with the covariates of age, atrial fibrillation, renal function, N-terminal pro-brain natriuretic peptide, and other echocardiographic parameters. We further divided the patients into 4 groups, first into 2 groups with a TAPSE/PASP either ≥ or < 0.46 mm/mm Hg, and then into 4 groups by RVD medians of 31.9 mm and 33.3 mm, respectively. Kaplan-Meier curve analysis showed that outcomes were worst in patients with a low TAPSE/PASP ratio and larger RVD (log-rank P < 0.0001). Conclusions: This multicentre observational study highlighted the further prognostic importance of larger RVD among HFpEF patients with RV-PA uncoupling. Résumé: Contexte: On sait que le découplage entre le ventricule droit (VD) et l’artère pulmonaire (AP) est important pour établir le pronostic de l’insuffisance cardiaque à fraction d’éjection réduite, mais également celui de l’insuffisance cardiaque à fraction d’éjection préservée (ICFEP). Nous avons étudié en détail les facteurs clés liés au pronostic défavorable de l'ICFEP chez les patients présentant un découplage VD-AP. Méthodologie: À partir des données d’une cohorte multicentrique, nous avons réalisé des analyses a posteriori sur 817 patients présentant une ICFEP qui sont sortis de l’hôpital en vie, avec comme critère d’évaluation principal la mortalité d’origine cardiaque ou la réadmission en raison de l’insuffisance cardiaque. Au total, 288 patients affichant un découplage VD-AP ont été observés, principalement ceux dont le rapport excursion systolique dans le plan annulaire tricuspide (TAPSE; tricuspid annular plane systolic excursion)-pression artérielle pulmonaire systolique (PAPs) était < 0,46 mm/mm Hg. Résultats: Au total, 101 événements indésirables ont été recensés sur une période médiane de 340 jours chez les patients qui présentaient un découplage VD-AP. La dimension ventriculaire droite mesurée par échocardiographie était un facteur pronostique significativement important dans les analyses de régression de Cox à une et à plusieurs variables (rapport des risques instantanés [RRI] : 1,044; intervalle de confiance à 95 % : 1,014 à 1,074; p : 0,0042; et RRI : 1,036; intervalle de confiance à 95 % : 1,001 à 1,072; p : 0,0438; respectivement) avec prise en compte des covariables de l’âge, de la fibrillation auriculaire, de la fonction rénale, du fragment N-terminal du propeptide natriurétique de type B, et d’autres paramètres échocardiographiques. Nous avons ensuite réparti les patients en quatre groupes, d’abord en deux groupes, selon que leur rapport TAPSE-PAPs était ≥ ou < 0,46 mm/mm Hg, puis en quatre groupes selon des dimensions ventriculaires droites médianes de 31,9 et de 33,3 mm, respectivement. L’analyse de la courbe de Kaplan-Meier a révélé des résultats moins favorables chez les patients qui présentaient un faible rapport TAPSE-PAPs et une grande dimension ventriculaire droite (valeur de p < 0,0001 selon le test du log-rank). Conclusions: Cette étude observationnelle multicentrique a mis en évidence l’importance d’une grande dimension ventriculaire droite dans l’établissement du pronostic chez les patients atteints d'ICFEP qui présentent un découplage VD-AP.
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- 2022
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32. Automated diagnosis of optical coherence tomography imaging on plaque vulnerability and its relation to clinical outcomes in coronary artery disease
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Hirohiko Niioka, Teruyoshi Kume, Takashi Kubo, Tsunenari Soeda, Makoto Watanabe, Ryotaro Yamada, Yasushi Sakata, Yoshihiro Miyamoto, Bowen Wang, Hajime Nagahara, Jun Miyake, Takashi Akasaka, Yoshihiko Saito, and Shiro Uemura
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Medicine ,Science - Abstract
Abstract This study sought to develop a deep learning-based diagnostic algorithm for plaque vulnerability by analyzing intravascular optical coherence tomography (OCT) images and to investigate the relation between AI-plaque vulnerability and clinical outcomes in patients with coronary artery disease (CAD). A total of 1791 study patients who underwent OCT examinations were recruited from a multicenter clinical database, and the OCT images were first labeled as either normal, a stable plaque, or a vulnerable plaque by expert cardiologists. A DenseNet-121-based deep learning algorithm for plaque characterization was developed by training with 44,947 prelabeled OCT images, and demonstrated excellent differentiation among normal, stable plaques, and vulnerable plaques. Patients who were diagnosed with vulnerable plaques by the algorithm had a significantly higher rate of both events from the OCT-observed segments and clinical events than the patients with normal and stable plaque (log-rank p
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- 2022
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33. Contemporary use of SGLT2 inhibitors in heart failure patients with diabetes mellitus: a comparison of DPP4 inhibitors in a nationwide electric health database of the superaged society
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Michikazu Nakai, Yoshitaka Iwanaga, Koshiro Kanaoka, Yoko Sumita, Yuichi Nishioka, Tomoya Myojin, Shinichiro Kubo, Katsuki Okada, Tsunenari Soeda, Tatsuya Noda, Yasushi Sakata, Tomoaki Imamura, Yoshihiko Saito, Satoshi Yasuda, and Yoshihiro Miyamoto
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Diabetes mellitus ,Nationwide Electric Health Database ,One-year prognosis ,An SGLT2 inhibitor ,Superaged society ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Background There is a lack of recent data reflecting the actual use of sodium-glucose cotransporter-2 (SGLT2) inhibitors for heart failure (HF) and type 2 diabetes (DM) in the superaged society. The present study investigated the association between the use of SGLT2 inhibitors and one-year prognosis in patients hospitalized across a broad spectrum of HF patients with DM in the superaged society using the Nationwide Electric Health Database in Japan. Methods The patients hospitalized with the first episode of acute HF were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan between April 2014 and March 2019. A cohort of 2,277 users of SGLT2 inhibitors and 41,410 users of the active comparator, dipeptidyl peptidase-4 (DPP4) inhibitors were compared. A propensity score-matched cohort study of 2,101 users of each inhibitor was also conducted. A multivariable multilevel mixed-effects survival model was conducted with adjustments, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Results Among 300,398 patients discharged with HF in 4,176 hospitals, 216,016 (71.9%) were 75 years or older, and 60,999 (20.3%) took antidiabetic medications. Among them, the patients treated with SGLT2 inhibitors were younger and had a more severe status than those treated with DPP4 inhibitors. Kaplan–Meier analysis showed that patients treated with SGLT2 inhibitors had a lower mortality risk and HF readmission. In propensity-matched cohorts, SGLT2 inhibitor use was associated with a lower risk of mortality and HF readmission than DPP-4 inhibitor use (HR [95% CI]; 0.70 [0.56, 0.89] and 0.52 [0.45, 0.61], respectively). Very elderly (≥ 75 years) patients showed similar results. Favorable effects were also observed across all age groups, including ≥ 75 years, in patients with coronary artery disease or atrial fibrillation and with concomitant β-blocker, diuretics, or insulin. Conclusion The use of SGLT2 inhibitors at discharge was associated with a lower risk of one-year mortality and HF readmission in patients across a broad spectrum of HF with DM in the superaged society. The findings further support the benefits of using SGLT2 inhibitors in very elderly HF care and complement the current evidence.
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- 2022
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34. Minimal subphenotyping model for acute heart failure with preserved ejection fraction
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Yohei Sotomi, Taiki Sato, Shungo Hikoso, Sho Komukai, Bolrathanak Oeun, Tetsuhisa Kitamura, Daisaku Nakatani, Hiroya Mizuno, Katsuki Okada, Tomoharu Dohi, Akihiro Sunaga, Hirota Kida, Masahiro Seo, Masamichi Yano, Takaharu Hayashi, Akito Nakagawa, Yusuke Nakagawa, Shunsuke Tamaki, Tomohito Ohtani, Yoshio Yasumura, Takahisa Yamada, Yasushi Sakata, and OCVC‐Heart Failure Investigator
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HFpEF ,Acute decompensated heart failure ,Phenotyping ,Minimal model ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims Application of the latent class analysis to acute heart failure with preserved ejection fraction (HFpEF) showed that the heterogeneous acute HFpEF patients can be classified into four distinct phenotypes with different clinical outcomes. This model‐based clustering required a total of 32 variables to be included. However, this large number of variables will impair the clinical application of this classification algorithm. This study aimed to identify the minimal number of variables for the development of optimal subphenotyping model. Methods and results This study is a post hoc analysis of the PURSUIT‐HFpEF study (N = 1095), a prospective, multi‐referral centre, observational study of acute HFpEF [UMIN000021831]. We previously applied the latent class analysis to the PURSUIT‐HFpEF dataset and established the full 32‐variable model for subphenotyping. In this study, we used the Cohen's kappa statistic to investigate the minimal number of discriminatory variables needed to accurately classify the phenogroups in comparison with the full 32‐variable model. Cohen's kappa statistic of the top‐X number of discriminatory variables compared with the full 32‐variable derivation model showed that the models with ≥16 discriminatory variables showed kappa value of >0.8, suggesting that the minimal number of discriminatory variables for the optimal phenotyping model was 16. The 16‐variable model consists of C‐reactive protein, creatinine, gamma‐glutamyl transferase, brain natriuretic peptide, white blood cells, systolic blood pressure, fasting blood sugar, triglyceride, clinical scenario classification, infection‐triggered acute decompensated HF, estimated glomerular filtration rate, platelets, neutrophils, GWTG‐HF (Get With The Guidelines‐Heart Failure) risk score, chronic kidney disease, and CONUT (Controlling Nutritional Status) score. Characteristics and clinical outcomes of the four phenotypes subclassified by the minimal 16‐variable model were consistent with those by the full 32‐variable model. The four phenotypes were labelled based on their characteristics as ‘rhythm trouble’, ‘ventricular‐arterial uncoupling’, ‘low output and systemic congestion’, and ‘systemic failure’, respectively. Conclusions The phenotyping model with top 16 variables showed almost perfect agreement with the full 32‐variable model. The minimal model may enhance the future clinical application of this clustering algorithm.
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- 2022
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35. Individual acute-phase bleeding and thrombotic risk balance assessment in patients undergoing percutaneous coronary intervention for acute myocardial infarction
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Yohei Sotomi, Shungo Hikoso, Sho Komukai, Tetsuhisa Kitamura, Daisaku Nakatani, Tomoharu Dohi, Hiroya Mizuno, Katsuki Okada, Hirota Kida, Bolrathanak Oeun, Akihiro Sunaga, Taiki Sato, Yuki Matsuoka, Yasuhiko Sakata, Hiroshi Sato, Masatsugu Hori, Issei Komuro, and Yasushi Sakata
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Myocardial infarction ,Bleeding ,Thrombosis ,Risk balance ,Calculator ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background: Individualized treatment approach based on pre-procedural precise risk balance assessment between bleeding and thrombosis would be desirable for patients with myocardial infarction (MI) undergoing emergent percutaneous coronary intervention (PCI) in this ultra-short dual antiplatelet therapy era. We aimed to develop and validate a quick thrombosis/bleeding risk-balance assessment tool. Methods: We developed and validated a novel thrombosis/bleeding risk-balance assessment tool using individual patient data from the prospective multicenter MI registry. Individual risks of thrombosis and bleeding within 7 days of the index PCI were estimated using a multinomial logistic regression model. The model was developed in the derivation cohort (4554 patients enrolled during 2003–2009) and validated in the validation cohort (2215 patients during 2010–2014). Results: A total of 6769 patients (66 ± 12 years, 5175 men) were eligible in this analysis. Predictive performance of the multinomial logistic regression models for bleeding and thrombosis assessed by calibration plots was good both in the derivation and validation cohorts. The net predicted probability (NPP) was defined as predicted probability of bleeding event (%) – predicted probability of thrombotic event (%). The NPP successfully stratified patients into those with a higher risk of bleeding than thrombosis and those with a higher risk of thrombosis than bleeding. This finding was consistent between the derivation and validation cohorts. Conclusions: We have established the risk balance assessment model for bleeding and thrombosis. Pre-procedural quick and precise assessment of the risk balance may help a decision making of procedural strategy and antithrombotic regimens in STEMI/non-STEMI patients undergoing PCI.
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- 2023
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36. Persistent Accelerated Infra-Hisian Escape Rhythm Masking Infra-Nodal Atrioventricular Block After Transcatheter Aortic Valve ImplantationNovel Teaching Points
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Takayuki Sekihara, MD, Takafumi Oka, MD, PhD, Kentaro Ozu, MD, and Yasushi Sakata, MD, PhD
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2023
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37. Delineation of an intra-isthmus reentry circuit around the coronary sinus ostium using an ultrahigh-resolution mapping system
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Takayuki Sekihara, Takafumi Oka, Kentaro Ozu, and Yasushi Sakata
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Atrial flutter ,Cavotricuspid isthmus ,Intra-isthmus reentry ,Ultrahigh-resolution mapping ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2023
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38. Relation of left atrial overload indices with prognostic endpoints in heart failure and preserved ejection fraction
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Shiro Hoshida, Koichi Tachibana, Yukinori Shinoda, Tomoko Minamisaka, Masahiro Seo, Masamichi Yano, Takaharu Hayashi, Akito Nakagawa, Yusuke Nakagawa, Shunsuke Tamaki, Takahisa Yamada, Yoshio Yasumura, Yohei Sotomi, Shungo Hikoso, Daisaku Nakatani, Yasushi Sakata, and OCVC‐Heart Failure Investigators
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Arterial elastance ,Diastolic elastance ,Elderly ,Endpoint ,HFpEF ,Prognosis ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims Considerable variation in the relationships between the indices of left atrial (LA) volume and pressure could possibly affect the selection of medications or efforts to improve the prognoses of patients with heart failure and preserved ejection fraction (HFpEF). We aimed to clarify the association between the prognostic endpoint and LA overload indices in elderly patients with HFpEF. Methods and results We analysed 898 patients with HFpEF hospitalized for acute decompensated heart failure (men/women: 406/492). Blood tests and transthoracic echocardiography were performed before discharge. The primary endpoint was re‐admission for heart failure or all‐cause mortality. Stroke volume (SV)/left atrial volume (LAV), an index for LA volume overload, was a significant prognostic factor of re‐admission for heart failure in the multivariable Cox hazard analysis adjusted for comorbidities [hazard ratio (HR) 0.616, 95% confidence interval (CI) 0.430–0.882, P = 0.008]. Additionally, the ratio of diastolic elastance (Ed) to arterial elastance (Ea), an index for LA pressure overload, was also significant (HR 1.444, 95% CI 1.014–2.058, P = 0.041). Furthermore, Ed/Ea, but not SV/LAV, was a significant prognostic factor of all‐cause mortality (HR 1.594, 95% CI 1.102–2.306, P = 0.013). Conclusions The index of LA overload for prognosis may differ according to the different endpoints in elderly patients with HFpEF.
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- 2022
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39. Primary results from the Japanese Heart Failure and Sudden Cardiac Death Prevention Trial (HINODE)
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Kazutaka Aonuma, Kenji Ando, Kengo Kusano, Toru Asai, Koichi Inoue, Yukihiro Inamura, Takanori Ikeda, Takeshi Mitsuhashi, Toyoaki Murohara, Nobuhiro Nishii, Akihiko Nogami, Wataru Shimizu, Caroline Beaudoint, Torri Simon, Torsten Kayser, Hussin Azlan, Ngarmukos Tachapong, Joseph Yat‐Sun Chan, Valentina Kutyifa, Yasushi Sakata, and For the HINODE Investigators
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Defibrillator therapy ,Ventricular arrhythmia ,Sudden cardiac death ,Japan, primary prevention ,Electrophysiologic studies ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims The HINODE study aimed to analyse rates of mortality, appropriately treated ventricular arrhythmias (VA), and heart failure in Japanese patients and compared with those in Western patients. Methods and results After treatment decisions following contemporary practice in Japan, patients were prospectively enrolled into four cohorts: (i) internal cardioverter‐defibrillator (ICD), (ii) cardiac resynchronization therapy (CRT) defibrillator (CRT‐D), (iii) standard medical therapy (‘non‐device’: ND), or (iv) pacing (indicated for CRT; received pacemaker or CRT pacing). Cohorts 1–3 required a left ventricular ejection fraction ≤35%, a history of heart failure, and a need for primary prevention of sudden cardiac death based on two to five previously identified risk factors. Endpoint outcomes were adjudicated by the independent committees. ICD and CRT‐D cohorts, considered as high‐voltage (HV) cohorts, were pooled for Kaplan–Meier analysis and propensity‐matched to Multicenter Automatic Defibrillator Implantation Trial‐Reduce Inappropriate Therapy (MADIT‐RIT) arm B and C patients. The study enrolled 354 patients followed for 19.6 ± 6.5 months, with a minimum of 12 months. Propensity‐matched HV cohorts showed comparable VA (P = 0.61) and mortality rates (P = 0.29) for HINODE and MADIT‐RIT. The ND cohort presented a high crossover rate to ICD therapy (6.1%, n = 7/115), and the CRT‐D cohort showed elevated mortality rates. The pacing cohort revealed that patients implanted with pacemakers had higher mortality (26.0%) than those with CRT‐Pacing (8.4%, P = 0.05). Conclusions The mortality and VA event rates of landmark trials are applicable to patients with primary prevention in Japan. Patients who did not receive guideline‐indicated CRT devices had poor outcomes.
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- 2022
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40. Association between prognosis and the use of angiotensin‐converting enzyme inhibitors and/or angiotensin II receptor blockers in frail patients with heart failure with preserved ejection fraction
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Akihiro Sunaga, Shungo Hikoso, Shunsuke Tamaki, Masahiro Seo, Masamichi Yano, Takaharu Hayashi, Akito Nakagawa, Yusuke Nakagawa, Hiroyuki Kurakami, Tomomi Yamada, Tetsuhisa Kitamura, Taiki Sato, Bolrathanak Oeun, Hirota Kida, Yohei Sotomi, Tomoharu Dohi, Katsuki Okada, Hiroya Mizuno, Daisaku Nakatani, Takahisa Yamada, Yoshio Yasumura, Yasushi Sakata, and OCVC‐Heart Failure Investigators
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Heart failure with preserved ejection fraction ,Clinical Frailty Scale ,ACE‐I ,ARB ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims The effectiveness of angiotensin‐converting enzyme inhibitors (ACE‐I) and angiotensin II receptor blockers (ARB) has not been demonstrated in patients with heart failure with preserved ejection fraction (HFpEF). We recently reported significant interaction between the use of ACE‐I and/or ARB (ACE‐I/ARB) and frailty on prognosis in patients with HFpEF. In the present study, we examined the association between ACE‐I/ARB and prognosis in patients with HFpEF stratified by the presence or absence of frailty. Methods and results We examined the association between the use of ACE‐I/ARB and prognosis according to the presence [Clinical Frailty Scale (CFS) ≥ 5] or absence (CFS ≤ 4) of frailty in patients with HFpEF in a post hoc analysis of registry data. Primary endpoint was the composite of all‐cause mortality and heart failure admission. Secondary endpoints were all‐cause mortality and heart failure admission. Of 1059 patients, median age was 83 years and 45% were male. Kaplan–Meier analysis showed that the risk of composite endpoint (log‐rank P = 0.001) and all‐cause death (log‐rank P = 0.005) in patients with ACE‐I/ARB was lower in those with CFS ≥ 5, but similar between patients with and without ACE‐I/ARB in patients with CFS ≤ 4 (composite endpoint: log‐rank P = 0.830; all‐cause death: log‐rank P = 0.192). In a multivariable Cox proportional hazards model, use of ACE‐I/ARB was significantly associated with lower risk of the composite endpoint [hazard ratio (HR) = 0.52, 95% confidence interval (CI) = 0.33–0.83, P = 0.005] and heart failure admission (HR = 0.45, 95% CI = 0.25–0.83, P = 0.010) in patients with CFS ≥ 5, but not in patients with CFS ≤ 4 (composite endpoint: HR = 1.41, 95% CI = 0.99–2.02, P = 0.059; heart failure admission: HR = 1.43, 95% CI = 0.94–2.18, P = 0.091). The association between ACE‐I or ARB and prognosis did not significantly differ by CFS (CFS ≤ 4: log‐rank P = 0.562; CFS ≥ 5: log‐rank P = 0.100, for with ACE‐I vs. ARB, respectively). Adjusted HRs for CFS 1–4 were higher than 1.0 but were
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- 2022
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41. Prognostic significance of serum chloride level in heart failure patients with preserved ejection fraction
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Masahiro Seo, Tetsuya Watanabe, Takahisa Yamada, Masamichi Yano, Takaharu Hayashi, Akito Nakagawa, Yusuke Nakagawa, Shunsuke Tamaki, Yoshio Yasumura, Yohei Sotomi, Shungo Hikoso, Daisaku Nakatani, Masatake Fukunami, and Yasushi Sakata
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Heart failure with preserved ejection fraction ,Serum chloride level ,Risk stratification ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims The prognostic value of serum chloride level has been reported primarily in patients with heart failure with reduced ejection fraction, and hence, there is limited evidence in patients of heart failure with preserved ejection fraction (HFpEF). This study was conducted to clarify the relationship between serum chloride level and clinical outcomes in patients with HFpEF with acute decompensated heart failure (ADHF). Methods and results Patient data were extracted from The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with Preserved Ejection Fraction (PURSUIT HFpEF) study, a prospective multicentre observational registry for ADHF‐HFpEF in Osaka. The data of 870 patients were analysed after excluding patients with in‐hospital death, missing follow‐up data, missing data of serum chloride level, or on chronic dialysis therapy. The primary endpoint of this study was all‐cause mortality. At discharge, right ventricular systolic dysfunction was significantly associated with the lowest tertile of serum chloride level after multivariable adjustment (P = 0.0257). During a mean follow‐up period of 1.8 ± 1.0 years, 186 patients died. Cox multivariable analysis showed that serum chloride level at discharge (P = 0.0017) was independently associated with all‐cause mortality after multivariable adjustment of major confounders, whereas serum sodium level was no longer significant (P = 0.6761). Kaplan–Meier survival curve analysis revealed a significantly increased risk of mortality stratified by the tertile of serum chloride level [29% vs. 19% vs. 16%, P = 0.0002; hazard ratio (HR): 2.09 (95% confidence interval, CI: 1.31 to 3.34), HR: 1.03 (95% CI: 0.65 to 1.64)]. Conclusions Serum chloride level was useful for the prediction of poor outcome in ADHF patients with preserved ejection fraction.
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- 2022
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42. Erratum to 'Twice- or once-daily dosing of direct oral anticoagulants and gastrointestinal bleeding in patient with atrial fibrillation' [Am. Heart J. Plus: Cardiol. Res. Pract. Volume 22, October 2022, 100203]
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Tadakiyo Ido, Shun Sasaki, Yohei Sotomi, Akio Hirata, Nobuhiko Makino, Takaharu Hayashi, Yasushi Sakata, Atsushi Hirayama, and Yoshiharu Higuchi
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Published
- 2023
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43. Combination of Neutrophil‐to‐Lymphocyte and Platelet‐to‐Lymphocyte Ratios as a Novel Predictor of Cardiac Death in Patients With Acute Decompensated Heart Failure With Preserved Left Ventricular Ejection Fraction: A Multicenter Study
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Shunsuke Tamaki, Yoshiyuki Nagai, Ryu Shutta, Daisaku Masuda, Shizuya Yamashita, Masahiro Seo, Takahisa Yamada, Akito Nakagawa, Yoshio Yasumura, Yusuke Nakagawa, Masamichi Yano, Takaharu Hayashi, Shungo Hikoso, Daisaku Nakatani, Yohei Sotomi, and Yasushi Sakata
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cardiac death ,heart failure with preserved ejection fraction ,inflammation ,prognosis ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background Neutrophil‐to‐lymphocyte ratio (NLR) and platelet‐to‐lymphocyte ratio (PLR) are novel inflammation markers. Their combined usefulness for estimating the prognosis of patients with heart failure with preserved ejection fraction (HFpEF) admitted for acute decompensated heart failure remains elusive. Methods and Results We investigated 1026 patients registered in the Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction. Both NLR and PLR values were measured at the time of admission. Comorbidity burden was defined as the number of occurrences of 8 common comorbidities of HFpEF. The primary end point was cardiac death. The patients were stratified into 3 groups based on the optimal cut‐off values of NLR and PLR on the receiver operating characteristic curve analysis for predicting cardiac death (low NLR and PLR, either high NLR or PLR, and both high NLR and PLR). After a median follow‐up of 429 days, 195 patients died, with 85 of these deaths attributed to cardiac causes. An increased comorbidity burden was significantly associated with a higher proportion of patients with high NLR (>4.5) or PLR (>193), or both. High NLR and PLR values were independently associated with cardiac death, and a combination of both values was the strongest predictor (hazard ratio, 2.66 [95% CI, 1.51–4.70], P=0.0008). A significant difference was found in the rate of cardiac death among the 3 groups stratified by NLR and PLR values. Conclusions The combination of NLR and PLR is useful for the prediction of postdischarge cardiac death in patients with acute HFpEF. Registration URL: ClinicalTrials.gov; Unique identifier: UMIN000021831.
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- 2023
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44. Pemafibrate suppresses NLRP3 inflammasome activation in the liver and heart in a novel mouse model of steatohepatitis-related cardiomyopathy
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Kotaro Kanno, Masahiro Koseki, Jiuyang Chang, Ayami Saga, Hiroyasu Inui, Takeshi Okada, Katsunao Tanaka, Masumi Asaji, Yinghong Zhu, Seiko Ide, Shigeyoshi Saito, Tomoaki Higo, Daisuke Okuzaki, Tohru Ohama, Makoto Nishida, Yoshihiro Kamada, Masafumi Ono, Toshiji Saibara, Shizuya Yamashita, and Yasushi Sakata
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Medicine ,Science - Abstract
Abstract Although patients with nonalcoholic fatty liver disease have been reported to have cardiac dysfunction, and appropriate model has not been reported. We established a novel mouse model of diet-induced steatohepatitis-related cardiomyopathy and evaluated the effect of pemafibrate. C57Bl/6 male mice were fed a (1) chow diet (C), (2) high-fat, high-cholesterol, high-sucrose, bile acid diet (NASH diet; N), or (3) N with pemafibrate 0.1 mg/kg (NP) for 8 weeks. In the liver, macrophage infiltration and fibrosis in the liver was observed in the N group compared to the C group, suggesting steatohepatitis. Free cholesterol accumulated, and cholesterol crystals were observed. In the heart, free cholesterol similarly accumulated and concentric hypertrophy was observed. Ultrahigh magnetic field magnetic resonance imaging revealed that the left ventricular (LV) ejection fraction (EF) was attenuated and LV strain was focally impaired. RNA sequencing demonstrated that the NOD-like receptor and PI3 kinase-Akt pathways were enhanced. mRNA and protein expression of inflammasome-related genes, such as Caspase-1, NLRP3, and IL-1β, were upregulated in both the liver and heart. In the NP compared to the N group, steatohepatitis, hepatic steatosis, and cardiac dysfunction were suppressed. Sequential administration of pemafibrate after the development of steatohepatitis-related cardiomyopathy recovered hepatic fibrosis and cardiac dysfunction.
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- 2022
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45. Rubicon-regulated beta-1 adrenergic receptor recycling protects the heart from pressure overload
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Yasuhiro Akazawa, Manabu Taneike, Hiromichi Ueda, Rika Kitazume-Taneike, Tomokazu Murakawa, Ryuta Sugihara, Hiroki Yorifuji, Hiroki Nishida, Kentaro Mine, Ayana Hioki, Shigemiki Omiya, Hiroyuki Nakayama, Osamu Yamaguchi, Tamotsu Yoshimori, Yasushi Sakata, and Kinya Otsu
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Medicine ,Science - Abstract
Abstract Heart failure has high morbidity and mortality in the developed countries. Autophagy is important for the quality control of proteins and organelles in the heart. Rubicon (Run domain Beclin-1-interacting and cysteine-rich domain-containing protein) has been identified as a potent negative regulator of autophagy and endolysosomal trafficking. The aim of this study was to investigate the in vivo role of Rubicon-mediated autophagy and endosomal trafficking in the heart. We generated cardiomyocyte-specific Rubicon-deficient mice and subjected the mice to pressure overload by means of transverse aortic constriction. Rubicon-deficient mice showed heart failure with left ventricular dilatation, systolic dysfunction and lung congestion one week after pressure overload. While autophagic activity was unchanged, the protein amount of beta-1 adrenergic receptor was decreased in the pressure-overloaded Rubicon-deficient hearts. The increases in heart rate and systolic function by beta-1 adrenergic stimulation were significantly attenuated in pressure-overloaded Rubicon-deficient hearts. In isolated rat neonatal cardiomyocytes, the downregulation of the receptor by beta-1 adrenergic agonist was accelerated by knockdown of Rubicon through the inhibition of recycling of the receptor. Taken together, Rubicon protects the heart from pressure overload. Rubicon maintains the intracellular recycling of beta-1 adrenergic receptor, which might contribute to its cardioprotective effect.
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- 2022
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46. Renoprotection by long‐term low‐dose tolvaptan in patients with heart failure and hyponatremia
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Tatsufumi Oka, Takayuki Hamano, Tomohito Ohtani, Yohei Doi, Karin Shimada, Ayumi Matsumoto, Satoshi Yamaguchi, Nobuhiro Hashimoto, Masamitsu Senda, Yusuke Sakaguchi, Isao Matsui, Kei Nakamoto, Fusako Sera, Shungo Hikoso, Yasushi Sakata, and Yoshitaka Isaka
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Tolvaptan ,Heart failure (HF) ,Renal function ,Hyponatremia ,Renal benefits ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims In previous randomized controlled trials, the use of tolvaptan (TLV) at a fixed dose of 30 mg/day for 1 year did not provide renal benefits in patients with heart failure (HF). This retrospective, cohort study examined the renoprotective effects of long‐term, flexible‐dose, and lower‐dose TLV use. Methods and results Tolvaptan users were defined as patients receiving TLV for at least 180 consecutive days or those who continued it until death, any cardiac events, or renal replacement therapy even if it was taken for
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- 2021
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47. Variability in estimated glomerular filtration rate and patients' outcomes in a real‐world heart failure population
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Tatsufumi Oka, Takayuki Hamano, Tomohito Ohtani, Akihiro Tanaka, Yohei Doi, Satoshi Yamaguchi, Masamitsu Senda, Yusuke Sakaguchi, Isao Matsui, Kei Nakamoto, Fusako Sera, Shungo Hikoso, Masami Nishino, Yasushi Sakata, and Yoshitaka Isaka
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Heart failure (HF) ,Risk prediction ,eGFR variability ,B‐type natriuretic peptide (BNP) ,Estimated glomerular filtration rate (eGFR) ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims The prognostic significance of renal function variability has not been fully elucidated in heart failure (HF). This multicentre, prospective cohort study aimed to evaluate the usefulness of visit‐to‐visit variability in estimated glomerular filtration rate (eGFR) for predicting patients' outcomes in a real‐world HF population. Methods A total of 564 patients who had survived HF hospitalization were randomly assigned with a 2:1 ratio to derivation and validation cohorts, and they were then followed after discharge. Using the data for 6 months after discharge, each patient's visit‐to‐visit eGFR variability (EGV) was estimated. In the derivation cohort, Cox regression analyses were performed to assess the association of EGV with a subsequent composite event (death and HF hospitalization). In the validation cohort, the predictive performance was compared among Cox regression models with EGV, those with B‐type natriuretic peptide (BNP) and those with eGFR. Results In the derivation cohort (376 patients), median age, left ventricular ejection fraction (LVEF), BNP and eGFR at discharge were 72 years, 53.3%, 134.8 pg/mL and 58.7 mL/min/1.73 m2, respectively. During a median follow‐up of 2.2 years, higher EGV was associated with an increased risk of the composite event (adjusted hazard ratio [per standard deviation increase in log‐transformed EGV], 1.5; 95% confidence interval, 1.1–2.0). A similar finding was observed in a stratified analysis by LVEF. In the validation cohort (188 patients), better model fit, discrimination, reclassification and calibration were observed for EGV than for 6‐month averaged BNP or eGFR for predicting the composite event when added to HF risk prediction models. Adding EGV to models with BNP or eGFR improved model discrimination and reclassification. Conclusions EGV predicts HF outcomes regardless of LVEF. Risk prediction models with EGV have good performance in real‐world HF patients. The study findings highlight the clinical importance of observing visit‐to‐visit fluctuations in renal function in this population.
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- 2021
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48. Impact of admission hyperglycaemia on clinical outcomes in non‐diabetic heart failure with preserved ejection fraction
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Masamichi Yano, Masami Nishino, Kohei Ukita, Akito Kawamura, Hitoshi Nakamura, Yutaka Matsuhiro, Koji Yasumoto, Masaki Tsuda, Naotaka Okamoto, Akihiro Tanaka, Yasuharu Matsunaga‐Lee, Yasuyuki Egami, Ryu Shutta, Jun Tanouchi, Takahisa Yamada, Yoshio Yasumura, Shunsuke Tamaki, Takaharu Hayashi, Akito Nakagawa, Yusuke Nakagawa, Tomoharu Dohi, Daisaku Nakatani, Shungo Hikoso, and Yasushi Sakata
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Heart failure with preserved ejection fraction ,Admission blood glucose ,Hyperglycaemia ,Prognosis ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Abstract Aims At present, the clinical significance of admission hyperglycaemia in heart failure with preserved ejection fraction (HFpEF) patients remains unknown. This study was designed to evaluate the relationship between admission hyperglycaemia and clinical outcome in HFpEF patients, especially in non‐diabetic patients. Methods and results We enrolled 486 non‐diabetic HFpEF (left ventricular ejection fraction ≥50%) patients hospitalized due to acute decompensated heart failure from the PURSUIT‐HFpEF registry, a prospective, multicentre observational study. We divided non‐diabetic patients into two groups, an admission hyperglycaemia group whose blood glucose on admission was ≥7.0 mmol/L (148 patients) and a normoglycaemic group whose blood glucose on admission was
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- 2021
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49. Age-dependent association of discharge heart-failure medications with clinical outcomes in a super-aged society
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Michikazu Nakai, Yoshitaka Iwanaga, Koshiro Kanaoka, Yoko Sumita, Yuichi Nishioka, Tomoya Myojin, Shinichiro Kubo, Katsuki Okada, Tsunenari Soeda, Tatsuya Noda, Yasushi Sakata, Tomoaki Imamura, Yoshihiko Saito, Satoshi Yasuda, and Yoshihiro Miyamoto
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Age ,Heart failure medication ,Nationwide claims database ,1-year prognosis ,Super-aged society ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Aims: Real-world evidence about heart failure (HF) medical care for elderly patients is limited. The aim of this study was to clarify the age-dependent associations of HF medications at discharge with clinical outcomes in a super-aged society using a real-world big database. Methods and results: Patients hospitalized with a first episode of acute HF in 2013–2019 were identified in a nationwide claims database in Japan and were analyzed based on the HF medications at discharge. Hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) for clinical outcomes were calculated after adjustment. Among 325,468 patients from 4351 hospitals, 130,230 (40.0 %) were aged ≥ 85 years. All-cause mortality and HF readmission rate within 1 year were 14 % and 23 %, respectively. β-Blockers and angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers (ACEI/ARB) uses were associated with lower mortality (HR [95 %CI]: 0.84 [0.83,0.86] and 0.73 [0.71,0.74], respectively) and HF readmission (0.98 [0.97,0.99] and 0.89 [0.88,0.90], respectively). The associations were attenuated as the age increased and, in β-blockers use, the favorable associations with mortality and HF readmission were not observed in patients with ≥ 95 years and ≥ 80 years, respectively. In contrast, mineralocorticoid receptor antagonists (MRA) use was associated only with lower HF readmission (0.83 [0.82,0.84]), which was not attenuated with increased age. Conclusions: The favorable associations of β-blockers and ACEI/ARB uses with mortality and HF readmission were age-dependently attenuated in patients across a broad spectrum of HF in a super-aged society. In contrast, positive impact of MRA use on HF readmission was not attenuated with aging.
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- 2022
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50. Lowering Uric Acid May Improve Prognosis in Patients With Hyperuricemia and Heart Failure With Preserved Ejection Fraction
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Masami Nishino, Yasuyuki Egami, Shodai Kawanami, Hiroki Sugae, Kohei Ukita, Akito Kawamura, Hitoshi Nakamura, Yutaka Matsuhiro, Koji Yasumoto, Masaki Tsuda, Naotaka Okamoto, Yasuharu Matsunaga‐Lee, Masamichi Yano, Jun Tanouchi, Takahisa Yamada, Yoshio Yasumura, Shunsuke Tamaki, Takaharu Hayashi, Akito Nakagawa, Yusuke Nakagawa, Yohei Sotomi, Daisaku Nakatani, Shungo Hikoso, and Yasushi Sakata
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heart failure with preserved ejection fraction ,hyperuricemia ,prognosis ,uric acid ,uric acid lowering therapy ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Background An association between uric acid (UA) and cardiovascular diseases, including heart failure (HF), has been reported. However, whether UA is a causal risk factor for HF is controversial. In particular, the prognostic value of lowering UA in patients with HF with preserved ejection fraction (HFpEF) is unclear. Methods and Results We enrolled patients with HFpEF from the PURSUIT‐HFpEF (Prospective Multicenter Observational Study of Patients With Heart Failure With Preserved Ejection Fraction) registry. We investigated whether UA was correlated with the composite events, including all‐cause mortality and HF rehospitalization, in patients with hyperuricemia and HFpEF (UA >7.0 mg/dL). Additionally, we evaluated whether lowering UA for 1 year (≥1.0 mg/dL) in them reduced mortality or HF rehospitalization. We finally analyzed 464 patients with hyperuricemia. In multivariable Cox regression analysis, UA was an independent determinant of composite death and rehospitalization (hazard ratio [HR], 1.15 [95% CI, 1.03–1.27], P=0.015). We divided them into groups with severe and mild hyperuricemia according to median estimated value of serum UA (8.3 mg/dL). Cox proportional hazards models revealed the incidence of all‐cause mortality was significantly higher in the group with severe hyperuricemia than in the group with mild hyperuricemia (HR, 1.73 [95% CI, 1.19–2.25], P=0.004). The incidence of all‐cause mortality was significantly decreased in the group with lowering UA compared with the group with nonlowering UA (HR, 1.71 [95% CI, 1.02–2.86], P=0.041). The incidence of urate‐lowering therapy tended to be higher in the group with lowering UA than in the group with nonlowering UA (34.9% versus 24.6%, P=0.06). Conclusions UA is a predictor for the composite of all‐cause death and HF rehospitalization in patients with hyperuricemia and HFpEF. In these patients, lowering UA, including the use of urate‐lowering therapy, may improve prognosis.
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- 2022
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