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Undernutrition has been identified as a poor prognostic factor in heart failure with preserved ejection fraction (HFpEF). This study aimed to evaluate the impact of changes in nutritional status from discharge to one year post-discharge on the prognosis of patients with HFpEF. Initially, 547 HFpEF cases were classified into a normal nutrition group (NN) (n = 130) and an undernutrition group (UN) (n = 417), according to Controlling Nutritional Status (CONUT) scores at discharge. These groups were further subdivided according to CONUT scores one year post-discharge into NN (G1, n = 88) and UN (G2, n = 42), and NN (G3, n = 147) and UN (G4, n = 270), respectively. The primary end point was defined as a composite of all-cause mortality or heart failure readmission after the visit one year post-discharge. Normal nutrition was defined as a CONUT score of 0 or 1, and undernutrition as a CONUT score of ≥ 2. We compared the incidence rates of the primary end point between G1 and G2, and G3 and G4, and identified predictors for abnormalization or normalization of CONUT score one year post-discharge, as well as covarying factors with change in CONUT. In a multivariable Cox proportional hazards model, abnormalization of CONUT score was associated with an increased risk of the primary end point (adjusted HR [hazard ratio]: 2.87, 95% CI [confidence interval]: 1.32-6.22, p = 0.008), while normalization of CONUT was associated with a reduced risk (adjusted HR: 0.40, 95% CI: 0.23-0.67, p < 0.001). In a multivariate logistic regression analysis of patients with normal nutrition at discharge, the Euro Qol 5 Dimension score was identified as an independent predictor for abnormalization of CONUT score one year post-discharge (OR: 0.06, 95% CI: 0.01-0.43, p = 0.023). Among patients with undernutrition at discharge, prior heart failure hospitalization was the independent predictor for normalization of CONUT score (OR: 0.36, 95% CI: 0.20-0.66, p < 0.001). In a multivariate linear regression analysis, independent covariates associated with changes in CONUT included hemoglobin (β = - 0.297, p < 0.001), C-reactive protein (β = 0.349, p < 0.001), and log NT-proBNP (β = 0.142, p < 0.001). Post-discharge abnormalization or normalization of CONUT scores has prognostic impact on patients with HFpEF. Changes in CONUT may independently correlate with changes in hematopoiesis, inflammation, and fluid retention., Competing Interests: Declarations. Conflict of interest: Shungo Hikoso has received remuneration from Daiichi Sankyo Company, Boehringer Ingelheim Japan, AstraZeneca K.K. and Bayer, and research funding from Roche Diagnostics, FUJIFILM Toyama Chemical and Bristol Myers Squibb. Hiroya Mizuno has received a department endowment from Terumo. Yohei Sotomi has received remuneration from Abbott Vascular Japan, Boston Scientific Japan, research funding from Abbott Vascular Japan, and a department endowment from Terumo. Yasushi Sakata has received remuneration from Otsuka Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo Company and AstraZeneca K.K., and research funding from Otsuka Pharmaceutical, Daiichi Sankyo Company, Mitsubishi Tanabe Pharma Corporation, Astellas Pharma, Kowa Company, Boehringer Ingelheim Japan, and Biotronik. The other authors (Akihiro Sunaga, Shunsuke Tamaki, Masahiro Seo, Masamichi Yano, Takaharu Hayashi, Akito Nakagawa, Yusuke Nakagawa, Hiroyuki Kurakami, Tomomi Yamada, Tetsuhisa Kitamura, Taiki Sato, Bolrathanak Oeun, Hirota Kida, Tomoharu Dohi, Katsuki Okada, Daisaku Nakatani, Takahisa Yamada, Yoshio Yasumura) have no conflicts of interest to report. Ethical approval: IRB information—Kansai Rosai Hospital Institutional Review Board (approval ID: 16co10g), Kawachi General Hospital Ethics Committee (approval ID unavailable, but approved on 26 Apr 2016), Osaka Rosai Hospital Ethics Committee (approval ID: 28-5), Higashiosaka City Medical Center Institutional Review Board (approval ID: 02-0313), Osaka Prefectural Hospital Organization Osaka General Medical Center Institutional Review Board (approval ID: 28-2002), Hyogo Prefectural Nishinomiya Hospital Ethics Committee (approval ID: H28-3), Ikeda Municipal Hospital Ethics Committee (approval ID: 3280), Kawanishi City Hospital Institutional Review Board (approval ID: 28001), Rinku General Medical Center Ethics Committee (approval ID: 27-40), Saiseikai Senri Hospital Ethics Committee (approval ID: 280304), Yao Municipal Hospital Institutional Review Board (approval ID: H28-6), Kawasaki Hospital Ethics Committee (approval ID unavail able, but approved on 12 May 2016), Minoh City Hospital Ethics Committee (approval ID unavailable, but approved on 24 May 2016), National Hospital Organization Osaka National Hospital Second Institutional Review Board (approval ID: 16024), Kano General Hospital Ethics Committee (approval ID unavailable, but approved on 9 June 2016), Toyonaka Municipal Hospital Ethics Committee (approval ID: 2016-04-02), Kinan Hospital Ethics Committee 121, Japan Community Health Care Organization Osaka Hospital Ethics Committee (approval ID: 2016-2), Kobe Ekisaikai Hospital Ethics Committee (approval ID: 2016-3), Sakurabashi Watanabe Hospital Ethics Committee (approval ID: 16-15), Sumitomo Hospital Research Ethics Committee (approval ID: 28-01), Suita Municipal Hospital Institutional Review Board (approval ID: 2017-8), Kinki Central Hospital Ethics Committee (approval ID: 288), Osaka Police Hospital Institutional Review Board (approval ID: 593), Japan Community Health Care Organization Hoshigaoka Medical Center Institutional Review Board (approval ID: 1618), National Hospital Organization Osaka Minami Medical Center Institutional Review Board (approval ID: 28-3), Japan Community Health Care Organization Osaka Minato Central Hospital Ethics Committee (approval ID unvailable, but approved on 10 June 2016), Amagasaki Chuo Hospital Ethics Committee (approval ID unavailable, but approved on 1 Aug 2017), Otemae Hospital Institutional Review Board (approval ID: 2017-020), Osaka University Hospital Clinical Research Review Committee (approval ID: 15471), Osaka International Cancer Institute Institutional Review Board (No.20097)., (© 2024. The Author(s).)

Objectives: N-terminal pro brain natriuretic peptide (NT-proBNP) is a biomarker for myocardial stress used in diagnosing and prognosticating heart failure (HF). However, its interpretation is complicated by clinical factors. This study aims to clarify the prognostic value of NT-proBNP in patients with heart failure with preserved ejection fraction (HFpEF), and risk-prediction cutoffs considering various clinical factors., Methods: The study utilized data of prospective multicenter observational Asian HFpEF registry. Patients with acute decompensated HF and left ventricular ejection fraction ≥ 50% were included. NT-proBNP levels were measured at discharge. The primary endpoint was a composite of all-cause death and hospitalization for HF within 1 year after discharge., Results: A total of 1,231 patients (83 [77, 87] years, 551 (45%) male) were enrolled, with 916 eligible patients analyzed. The median NT-proBNP level was 1,060 pg/m. In multivariable logistic regression model, NT-proBNP was significantly associated with the primary endpoint (adjusted OR for log-transformed NT-proBNP:2.71, 95%CI:1.78-4.18, p<0.001). Subgroup analysis revealed varying NT-proBNP distributions and differential safety cutoffs (329-929 pg/mL) at sensitivity of 0.8 based on factors like atrial fibrillation and chronic kidney disease, maintaining its discriminatory performance (Area under the curve: 0.587-0.734)., Conclusions: NT-proBNP at discharge is a significant prognostic marker for HFpEF. Although NT-proBNP showed different distributions in various subgroups and cutoff values were distinctive for each, the prognostic utility was found to be equivalent in almost all subgroups with similar moderate discriminative performance. The study highlights the necessity of personalized NT-proBNP cutoffs for better management and prognostication of HFpEF., Competing Interests: Declaration of competing interest Y. Sotomi has received grants from Roche Diagnostics, FUJIFILM Toyama Chemical, TOA EIYO, Bristol-Myers Squibb, Biosense Webster, Abbott Medical Japan, and NIPRO, and personal fees from Abiomed, AstraZeneca, Amgen Astellas BioPharma, Biosensors, Boehringer Ingelheim, Bristole-Myers Squibb, Abbott Medical Japan, Boston Scientific Japan, Bayer, Daiichi Sankyo, Novartis, TERUMO, Medtronic, and Pfizer Pharmaceuticals. S. Hikoso has received personal fees from Daiichi Sankyo Company, Bayer, Astellas Pharma, Pfizer Pharmaceuticals, Novartis Pharmaceuticals, Kowa Company, Otsuka Pharmaceutical, AstraZeneca, Eli Lilly Japan, Ono Pharmaceutical, TOA EIYO, Kyowa Kirin, and Boehringer Ingelheim Japan that include speaking and lecture fees. S. Hikoso has received grants from Roche Diagnostics, FUJIFILM Toyama Chemical, TOA EIYO, and Bristol Myers Squibb. D. Nakatani has received personal fees from Roche Diagnostics. Y. Sakata has received personal fees from Otsuka Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, AstraZeneca K.K. and Actelion Pharmaceuticals, and grants from Roche Diagnostic, FUJIFILM Toyama Chemical, Bristol-Myers Squibb, Co, Biosense Webster, Inc., Abbott Medical Japan, Otsuka Pharmaceutical, Daiichi Sankyo Company, Mitsubishi Tanabe Pharma Corporation, Astellas Pharma, Kowa Company, Boehringer Ingelheim Japan, and Biotronik. The other authors have nothing to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Objectives : Coronary microvascular dysfunction (CMD) is associated with many heart diseases, including heart failure (HF) with preserved ejection fraction (HFpEF). Invasive examinations for CMD detection are difficult in older patients with HFpEF, and the decision criteria for noninvasive CMD measurements are unclear. We aimed to identify alternative factors in the possible involvement of CMD in the progression and prognosis of HFpEF. Methods : We analyzed 607 patients with HFpEF who were hospitalized for acute decompensated HF without a history of coronary artery disease (CAD). Blood tests and transthoracic echocardiography were performed. We focused on left ventricular hypertrophy (LVH) and coronary perfusion pressure (diastolic blood pressure, dBP). Results : The patients with LVH showed reduced diastolic function (E/e') and a lower incidence of atrial fibrillation (AF) compared with those without LVH, with no differences in age or dBP. No differences were observed in all-cause mortality between patients with low and high dBP without LVH. In the patients with LVH, the incidence of all-cause mortality was significantly higher, with a lower incidence of AF, reduced renal function, and higher C-reactive protein levels in those with low dBP than in those with high dBP. The comprehensive diastolic functional index, diastolic elastance/arterial elastance, was markedly higher in the patients with LVH, especially in those with all-cause mortality. This index, but not E/e', was a significant prognostic index in the multivariate Cox hazard analysis when adjusting for age, sex and N-terminal pro-brain natriuretic peptide levels. Conclusions : LVH and dBP were clinically important factors in elderly HFpEF patients without a history of CAD.

Aims: Anaemia has been reported as poor predictor in heart failure with preserved ejection fraction (HFpEF). The aim of this study was to evaluate the impact of changes in haemoglobin (Hb) from discharge to 1 year after discharge on the prognosis using a lower cut-off value of Hb than the World Health Organization (WHO) criteria., Methods and Results: First, 547 HFpEF cases were divided into two groups, Hb < 11.0 g/dL (n = 218) and Hb ≥ 11.0 g/dL (n = 329), according to Hb at discharge, and further were divided according to Hb 1 year after discharge into Hb < 11.0 g/dL (G1, n = 113), Hb ≥ 11.0 g/dL (G2, n = 105), Hb < 11.0 g/dL (G3, n = 66), and Hb ≥ 11.0 g/dL (G4, n = 263), respectively. Major adverse cardiovascular events (MACE) was defined as composite of all-cause death and heart failure readmission after a visit 1 year after discharge. The cut-off value of Hb was analysed by the receiver operating characteristics curve that predicts MACE. We examined the incidence rate of MACE between G4 and other subgroups and verified predictors of improving or worsening anaemia and covarying factors with change in Hb. In multivariate Cox proportional hazard model, MACE was significantly higher in G3 with worsening anaemia from Hb ≥ 11.0 g/dL to <11.0 g/dL than G4 with persistently Hb ≥ 11 g/dL (adjusted hazard ratio (HR): 3.14 [95% confidence interval (CI), 1.76-5.60], P < 0.001). MACE was not significantly different between G2 with improving anaemia from Hb < 11.0 g/dL to ≥ 11.0 g/dL and G4 (adjusted HR: 1.37 [95% CI, 0.68-2.75], P = 0.38). In multivariate logistic regression analysis, independent predictors of improving anaemia were male [odds ratio (OR): 0.45], chronic obstructive pulmonary disease (OR: 10.3), prior heart failure hospitalization (OR: 0.38), and estimated glomerular filtration rate (OR: 1.04). Independent predictors of worsening anaemia were age (OR: 1.07), body mass index (BMI) (OR: 0.86), clinical frailty scale score (OR: 1.29), Hb at discharge (OR: 0.63), and use of angiotensin-converting-enzyme inhibitor or angiotensin II receptor blocker (OR: 2.76). In multivariate linear regression analysis, covarying factors with change in Hb were BMI (β = -0.098), serum albumin (β = 0.411), and total cholesterol (β = 0.179)., Conclusions: Change in haemoglobin after discharge using a lower cut-off value than WHO criteria has prognostic impact in patients with HFpEF., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: In patients with persistent atrial fibrillation (AF), extensive ablation for substrate modification, such as linear ablation or complex fractionated atrial electrogram ablation in addition to pulmonary vein isolation (PVI) remains controversial. Previous studies investigating extensive ablation have demonstrated its varying efficacy, suggesting the possible heterogeneity of its efficacy. Aging is a major risk factor for AF and is associated with atrial remodeling. We aimed to compare the efficacy and safety of the extensive ablation strategy compared with PVI alone strategy between young and elderly patients., Methods: This study is a post-hoc analysis of the multicenter, randomized controlled, noninferiority trial investigating the efficacy and safety of PVI-only (PVI-alone arm) compared with extensive ablation (PVI-plus arm) in patients with persistent AF (EARNEST-PVI trial). We divided the overall population into 2 groups based on age and assessed treatment effects., Results: In the young group (age <65 years, N = 206), there was no significant difference in the recurrence rate between the PVI-alone group and PVI-plus group [hazard ratio (HR): 1.00, 95 % CI: 0.57-1.73, p = 0.987], whereas the recurrence rate was significantly lower in the PVI-plus group compared to the PVI-alone group in the elderly group (age ≥65 years, N = 291) (HR: 0.47, 95 % CI: 0.29-0.76, p = 0.0021) (p for interaction = 0.0446). There were no fatal procedural complications., Conclusion: In patients with persistent AF, the extensive ablation strategy was more effective than the PVI-alone strategy in elderly patients, while the effectiveness of both approaches was comparable in young patients., Trial Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT03514693. URL: https://center6.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000022454 Unique ID issued by UMIN: UMIN000019449., Competing Interests: Declaration of competing interest Y. Sotomi has received grants from Roche Diagnostics, FUJIFILM Toyama Chemical, TOA EIYO, Bristol-Myers Squibb, Biosense Webster, Abbott Medical Japan, and NIPRO, and personal fees from Abiomed, Abbott Medical Japan, AstraZeneca, Amgen Astellas BioPharma, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Boston Scientific Japan, Bayer, Daiichi Sankyo, Eli Lilly, Novartis, TERUMO, Medtronic, and Pfizer Pharmaceuticals. S. Hikoso has received grants from Roche Diagnostics, FUJIFILM Toyama Chemical, Actelion Pharmaceuticals; and personal fees from AstraZeneca, Daiichi Sankyo, Astellas Pharma, Bayer, Pfizer Pharmaceuticals, Boehringer Ingelheim Japan, Kowa Company, and Ono Pharmaceutical. D. Nakatani has received personal fees from Roche Diagnostics. T. Dohi has received grants from Medtronic, Johnson & Johnson, and Abbott, during the conduct of the study. A. Sunaga has received grants from Medtronic, Johnson & Johnson, and Abbott, during the conduct of the study and personal fees from Bayer, Daiichi Sankyo, and Medtronic, outside the submitted work. M. Masuda has received personal fees from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Johnson & Johnson, Boston Scientific, Abbott, Nihon Kohden, Otsuka Pharmaceutical, AstraZeneca, and Medtronic, outside the submitted work. T. Watanabe has received personal fees from Biosense Webster, Abbott, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, Bayer, Daiichi Sankyo, Nihon Kohden, and Fukuda Denshi, outside the submitted work. H. Minamiguchi has received grants from Medtronic, Johnson & Johnson, and Abbott, during the conduct of the study, and personal fees from Medtronic, Abbott, Johnson & Johnson, Nihon Kohden, Biotronik, Japan Lifeline, Daiichi Sankyo, Bayer, Pfizer, Squibb, Boehringer Ingelheim, Kowa, Ono Pharmaceutical, and Otsuka Pharmaceutical, outside the submitted work. Y. Egami has received personal fees from Japan Lifeline and Medtronic, and non-financial support from Johnson & Johnson, Abbott, and Medtronic, outside the submitted work; T. Oka has received personal fees from Medtronic, Biotronik, Abbott, Daiichi Sankyo, Beyer, Bristol-Myers Squibb, Boehringer Ingelheim, MSD, and AstraZeneca, outside the submitted work. Y. Matsuda has received personal fees from Daiichi Sankyo, Boehringer Ingelheim, Bayer, Medtronic, and Biotronik, outside the submitted work. M. Kawasaki has received personal fees from Medtronic, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Bristol-Myers Squibb, and Abbott, and grants from Osaka Heart Club, outside the submitted work. K. Inoue has received personal fees from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Johnson & Johnson, and Medtronic, outside the submitted work. Y. Sakata has received personal fees from Otsuka Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, AstraZeneca K.K. and Actelion Pharmaceuticals, and grants from Roche Diagnostic, FUJIFILM Toyama Chemical, Bristol-Myers Squibb, Co, Biosense Webster, Inc., Abbott Medical Japan, Otsuka Pharmaceutical, Daiichi Sankyo Company, Mitsubishi Tanabe Pharma Corporation, Astellas Pharma, Kowa Company, Boehringer Ingelheim Japan, and Biotronik. Other authors have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Extensive ablation in addition to pulmonary vein isolation (PVI) in patients with persistent atrial fibrillation (AF) has not yielded consistent results, indicating diversity in their efficacy. Mitral regurgitation (MR) associated with AF may indicate a higher prevalence of arrhythmogenic substrate, suggesting potential benefits of extensive ablation for these patients., Methods: This post-hoc analysis of the EARNEST-PVI trial compared PVI alone versus an extensive ablation strategy (PVI-plus) in persistent AF patients, stratified by MR presence. The primary endpoint of the study was the recurrence of AF. The secondary endpoints included death, cerebral infarction, and procedure-related complications., Results: The trial included 495 eligible patients divided into MR and non-MR groups. The MR group consisted of 192 patients (89 in the PVI-alone arm and 103 in the PVI-plus arm), while the non-MR group had 303 patients (158 in the PVI-alone arm and 145 in the PVI-plus arm). In the non-MR group, recurrence rates were similar between PVI-alone and PVI-plus arms (Log-rank P = 0.47, Hazard ratio = 0.85 [95%CI: 0.54-1.33], P = 0.472). However, in the MR group, PVI-plus was significantly more effective in preventing AF recurrence (Log-rank P = 0.0014, Hazard ratio = 0.40 [95%CI: 0.22-0.72], P = 0.0021). No significant differences were observed in secondary endpoints between the two arms., Conclusions: For persistent AF patients with mild or greater MR, receiving PVI-plus was superior to PVI-alone in preventing AF recurrence. Conversely, for patients without MR, the effectiveness of extensive ablation was not demonstrated. These findings suggest tailoring ablation strategies based on MR presence can lead to better outcomes in AF management., Competing Interests: Declaration of competing interest Y. Sotomi has received grants from Roche Diagnostics, FUJIFILM Toyama Chemical, TOA EIYO, Bristol-Myers Squibb, Biosense Webster, Abbott Medical Japan, and NIPRO, and personal fees from Abiomed, Abbott Medical Japan, AstraZeneca, Amgen Astellas BioPharma, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Boston Scientific Japan, Bayer, Daiichi Sankyo, Eli Lilly, Novartis, TERUMO, Medtronic, and Pfizer Pharmaceuticals. S. Hikoso has received grants from Roche Diagnostics, FUJIFILM Toyama Chemical, Actelion Pharmaceuticals; and personal fees from AstraZeneca, Daiichi Sankyo, Astellas Pharma, Bayer, Pfizer Pharmaceuticals, Boehringer Ingelheim Japan, Kowa Company, and Ono Pharmaceutical. D. Nakatani has received personal fees from Roche Diagnostics. T. Dohi has received grants from Medtronic, Johnson & Johnson, and Abbott, during the conduct of the study. A. Sunaga has received grants from Medtronic, Johnson & Johnson, and Abbott, during the conduct of the study and personal fees from Bayer, Daiichi Sankyo, and Medtronic, outside the submitted work. M. Masuda has received personal fees from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Johnson & Johnson, Boston Scientific, Abbott, Nihon Kohden, Otsuka Pharmaceutical, AstraZeneca, and Medtronic, outside the submitted work. T. Watanabe has received personal fees from Biosense Webster, Abbott, Bristol-Myers Squibb, Pfizer, Boehringer Ingelheim, Bayer, Daiichi Sankyo, Nihon Kohden, and Fukuda Denshi, outside the submitted work. H. Minamiguchi has received grants from Medtronic, Johnson & Johnson, and Abbott, during the conduct of the study, and personal fees from Medtronic, Abbott, Johnson & Johnson, Nihon Kohden, Biotronik, Japan Lifeline, Daiichi Sankyo, Bayer, Pfizer, Squibb, Boehringer Ingelheim, Kowa, Ono Pharmaceutical, and Otsuka Pharmaceutical, outside the submitted work. Y. Egami has received personal fees from Japan Lifeline and Medtronic, and non-financial support from Johnson & Johnson, Abbott, and Medtronic, outside the submitted work; T. Oka has received personal fees from Medtronic, Biotronik, Abbott, Daiichi Sankyo, Beyer, Bristol-Myers Squibb, Boehringer Ingelheim, MSD, and AstraZeneca, outside the submitted work. Y. Matsuda has received personal fees from Daiichi Sankyo, Boehringer Ingelheim, Bayer, Medtronic, Boston Scientific Japan, Japan Lifeline, Asahi Kasei ZOLL Medical, Synaptic Medical Japan and Biotronik, outside the submitted work. M. Kawasaki has received personal fees from Medtronic, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Bristol-Myers Squibb, and Abbott, and grants from Osaka Heart Club, outside the submitted work. K. Inoue has received personal fees from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Johnson & Johnson, and Medtronic, outside the submitted work. Y. Sakata has received personal fees from Otsuka Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, AstraZeneca K.K. and Actelion Pharmaceuticals, and grants from Roche Diagnostic, FUJIFILM Toyama Chemical, Bristol-Myers Squibb, Co, Biosense Webster, Inc., Abbott Medical Japan, Otsuka Pharmaceutical, Daiichi Sankyo Company, Mitsubishi Tanabe Pharma Corporation, Astellas Pharma, Kowa Company, Boehringer Ingelheim Japan, and Biotronik. Other authors have nothing to disclose., (Copyright © 2023. Published by Elsevier B.V.)

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., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The association between care needs level (CNL) at hospitalisation and postdischarge outcomes in older patients with acute heart failure (aHF) has been insufficiently investigated., Methods: This population-based cohort study was conducted using health insurance claims and CNL data of the Longevity Improvement & Fair Evidence study. Patients aged ≥65 years, discharged after hospitalisation for aHF between April 2014 and March 2022, were identified. CNLs at hospitalisation were classified as no care needs (NCN), support level (SL) and CNL1, CNL2-3 and CNL4-5 based on total estimated daily care time as defined by national standard criteria, and varied on an ordinal scale between SL&CNL1 (low level) to CNL4-5 (fully dependent). The primary outcomes were changes in CNL and death 1 year after discharge, assessed by CNL at hospitalisation using Cox proportional hazard models., Results: Of the 17 724 patients included, 7540 (42.5%), 4818 (27.2%), 3267 (18.4%) and 2099 (11.8%) had NCN, SL&CNL1, CNL2-3 and CNL4-5, respectively, at hospitalisation. One year after discharge, 4808 (27.1%), 3243 (18.3%), 2968 (16.7%), 2505 (14.1%) and 4200 (23.7%) patients had NCN, SL&CNL1, CNL2-3, CNL4-5 and death, respectively. Almost all patients' CNLs worsened after discharge. Compared to patients with NCN at hospitalisation, patients with SL&CNL1, CNL2-3 and CNL4-5 had an increased risk of all-cause death 1 year after discharge (hazard ratio [95% confidence interval]: 1.19 [1.09-1.31], 1.88 [1.71-2.06] and 2.56 [2.31-2.84], respectively)., Conclusions: Older patients with aHF and high CNL at hospitalisation had a high risk of all-cause mortality in the year following discharge., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: It has not been fully elucidated which patients with persistent atrial fibrillation (PerAF) should undergo substrate ablation plus pulmonary vein isolation (PVI). This study aimed to identify PerAF patients who required substrate ablation using intraprocedural assessment of the baseline rhythm and the origin of atrial fibrillation (AF) triggers., Methods and results: This was a post hoc subanalysis using extended data of the EARNEST-PVI trial, a prospective multicenter randomized trial comparing PVI-alone and PVI-plus (i.e., PVI with added catheter ablation) arms. We divided 492 patients into 4 groups according to baseline rhythm and the location of AF triggers before PVI: Group A (n=22), sinus rhythm with pulmonary vein (PV)-specific AF triggers (defined as reproducible AF initiation from PVs only); Group B (n=211), AF with PV-specific AF triggers; Group C (n=94), sinus rhythm with no PV-specific AF trigger; Group D (n=165), AF with no PV-specific AF trigger. Among the 4 groups, only in Group D (AF at baseline and no PV-specific AF triggers) was arrhythmia-free survival significantly lower in the PVI-alone than PVI-plus arm (P=0.032; hazard ratio 1.68; 95% confidence interval 1.04-2.70)., Conclusions: Patients with sinus rhythm or PV-specific AF triggers did not receive any benefit from substrate ablation, whereas patients with AF and no PV-specific AF trigger benefited from substrate ablation.

Background: The optimal duration of atrial fibrillation (AF) persistence for predicting poor outcomes after catheter ablation of long-standing AF (LsAF) and the best ablation strategy for these patients remain unclear., Objective: We aimed to assess the impact of the duration of AF persistence on outcomes after catheter ablation of AF., Methods: We analyzed the Efficacy of Pulmonary Vein Isolation Alone in Patients with Persistent Atrial Fibrillation (EARNEST-PVI) trial data comparing pulmonary vein isolation (PVI) alone (PVI-alone) with additional linear ablation or defragmentation (PVI-plus) in persistent AF (PerAF). Patients who received catheter ablation by contact force-sensing catheter were enrolled in the study. In patients with LsAF, the optimal cutoff duration of AF persistence was evaluated. With use of the threshold, patients with LsAF were divided into 2 groups and compared with PerAF <1 year for arrhythmia-free survival after a 3-month blanking period., Results: The optimal cutoff duration was 2.4 years. Of 458 patients, arrhythmia-free survival rates for LsAF 1-2.4 years were comparable to those of PerAF (hazard ratio [HR], 1.01; 95% CI, 0.67-1.52). However, LsAF >2.4 years had a higher recurrence risk than PerAF (HR, 2.22; 95% CI, 1.42-3.47). In LsAF >2.4 years, the PVI-plus strategy showed advantages over the PVI-alone strategy (HR, 0.36; 95% CI, 0.14-0.89). However, the interaction effect between LsAF 1-2.4 years and LsAF >2.4 years did not reach statistical significance (P = .116)., Conclusion: Whereas LsAF 1-2.4 years has similar outcomes to those of PerAF, LsAF >2.4 years was linked to higher arrhythmia recurrence risks. For LsAF >2.4 years, the PVI-plus strategy showed a potential to be superior to the PVI-alone strategy., Competing Interests: Disclosures Drs Minamiguchi, Dohi, Nakatani, Hikoso, and Sakata have received grants from Medtronic, Johnson & Johnson, and Abbott during the conduct of the study. Other authors have nothing to disclose related to the submitted work. Conflict of interest outside the submitted work is found in a supplemental file., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

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 < 0.001). Kaplan-Meier analysis showed that the groups with an LEP score of 2 had higher risk of the composite endpoint than those with an LEP score of 0 or 1 (P < 0.001, and P = 0.013, respectively), while those with an LEP score of 3 had higher risk than those with an LEP score of 0, 1 or 2 (P < 0.001, P < 0.001 and P = 0.020, respectively). Cox proportional hazards analysis showed that an LEP score of 3 was significantly associated with the composite endpoint (P = 0.030). Kaplan-Meier analysis showed that risk of the composite of all-cause death and HF readmission was significantly higher in low LDL values (less than the cut-off values as calculated by receiver operating characteristic curve analysis) patients with statin use than in those without statin use (log rank P = 0.002)., Conclusions: LEP score, which comprehensively reflects extra-cardiac co-morbidities, is significantly associated with clinical outcomes in HFpEF patients., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The effectiveness of β-blocker in patients with heart failure with preserved ejection fraction (HFpEF) remains to be determined. We aimed to clarify the association between the use of β-blocker and prognosis according to the status of frailty., Methods: We compared prognosis between HFpEF patients with and without β-blockers stratified with the Clinical Frailty Scale (CFS), using data from the PURSUIT-HFpEF registry (UMIN000021831)., Results: Among 1159 patients enrolled in the analysis (median age, 81.4 years; male, 44.7%), 580 patients were CFS ≤ 3, while 579 were CFS ≥ 4. Use of β-blockers was associated with a worse composite endpoint of all-cause death and heart failure readmission in patients with CFS ≥ 4 (adjusted hazard ratio (HR) 1.43, 95% CI 1.10-1.85, p = 0.007), but was not significantly associated with this endpoint in those with CFS ≤ 3 (adjusted HR 0.95, 95% CI 0.71-1.26, p = 0.719) in multivariable Cox proportional hazard models. These results were confirmed in a propensity-matched analysis (HR in those with CFS ≥ 4: 1.42, 95% CI 1.05-1.90, p = 0.020; that in those with CFS ≤ 3: 0.83, 95% CI 0.60-1.14, p = 0.249), and in an analysis in which patients were divided into CFS ≤ 4 and CFS ≥ 5., Conclusions: Use of β-blockers was significantly associated with worse prognosis specifically in patients with HFpEF and high CFS, but not in those with low CFS. Use of β-blockers in HFpEF patients with frailty may need careful attention., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Vessel-level physiological data derived from pressure wire measurements are one of the important determinant factors in the optimal revascularisation strategy for patients with multivessel disease (MVD). However, these may result in complications and a prolonged procedure time., Aims: The feasibility of using the quantitative flow ratio (QFR), an angiography-derived fractional flow reserve (FFR), in Heart Team discussions to determine the optimal revascularisation strategy for patients with MVD was investigated., Methods: Two Heart Teams were randomly assigned either QFR- or FFR-based data of the included patients. They then discussed the optimal revascularisation mode (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) for each patient and made treatment recommendations. The primary endpoint of the trial was the level of agreement between the treatment recommendations of both teams as assessed using Cohen's kappa., Results: The trial included 248 patients with MVD from 10 study sites. Cohen's kappa in the recommended revascularisation modes between the QFR and FFR approaches was 0.73 [95% confidence interval {CI} : 0.62-0.83]. As for the revascularisation planning, agreements in the target vessels for PCI and CABG were substantial for both revascularisation modes (Cohen's kappa=0.72 [95% CI: 0.66-0.78] and 0.72 [95% CI: 0.66-0.78], respectively). The team assigned to the QFR approach provided consistent recommended revascularisation modes even after being made aware of the FFR data (Cohen's kappa=0.95 [95% CI:0.90-1.00])., Conclusions: QFR provided feasible physiological data in Heart Team discussions to determine the optimal revascularisation strategy for MVD. The QFR and FFR approaches agreed substantially in terms of treatment recommendations.

Aims: Blood stasis is crucial in developing left atrial (LA) thrombi. LA appendage peak flow velocity (LAAFV) is a quantitative parameter for estimating thromboembolic risk. However, its impact on LA thrombus resolution and clinical outcomes remains unclear., Methods and Results: The LAT study was a multicentre observational study investigating patients with atrial fibrillation (AF) and silent LA thrombi detected by transoesophageal echocardiography (TEE). Among 17 436 TEE procedures for patients with AF, 297 patients (1.7%) had silent LA thrombi. Excluding patients without follow-up examinations, we enrolled 169 whose baseline LAAFV was available. Oral anticoagulation use increased from 85.7% at baseline to 97.0% at the final follow-up (P < 0.001). During 1 year, LA thrombus resolution was confirmed in 130 (76.9%) patients within 76 (34-138) days. Conversely, 26 had residual LA thrombi, 8 had thromboembolisms, and 5 required surgical removal. These patients with failed thrombus resolution had lower baseline LAAFV than those with successful resolution (18.0 [15.8-22.0] vs. 22.2 [17.0-35.0], P = 0.003). Despite limited predictive power (area under the curve, 0.659; P = 0.001), LAAFV ≤ 20.0 cm/s (best cut-off) significantly predicted failed LA thrombus resolution, even after adjusting for potential confounders (odds ratio, 2.72; 95% confidence interval, 1.22-6.09; P = 0.015). The incidence of adverse outcomes including ischaemic stroke/systemic embolism, major bleeding, or all-cause death was significantly higher in patients with reduced LAAFV than in those with preserved LAAFV (28.4% vs. 11.6%, log-rank P = 0.005)., Conclusion: Failed LA thrombus resolution was not rare in patients with AF and silent LA thrombi. Reduced LAAFV was associated with failed LA thrombus resolution and adverse clinical outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: The heterogeneous pathophysiology of the diverse heart failure with preserved ejection fraction (HFpEF) phenotypes needs to be examined. We aim to assess differences in the biomarkers among the phenotypes of HFpEF and investigate its multifactorial pathophysiology., Methods: This study is a retrospective analysis of the PURSUIT-HFpEF Study (N=1231), an ongoing, prospective, multicentre observational study of acute decompensated HFpEF. In this registry, there is a predefined subcohort in which we perform multibiomarker tests (N=212). We applied the previously established machine learning-based clustering model to the subcohort with biomarker measurements to classify them into four phenotypes: phenotype 1 (n=69), phenotype 2 (n=49), phenotype 3 (n=41) and phenotype 4 (n=53). Biomarker characteristics in each phenotype were evaluated., Results: Phenotype 1 presented the lowest value of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive C reactive protein, tumour necrosis factor-α, growth differentiation factor (GDF)-15, troponin T and cystatin C, whereas phenotype 2, which is characterised by hypertension and cardiac hypertrophy, showed the highest value of these markers. Phenotype 3 showed the second highest value of GDF-15 and cystatin C. Phenotype 4 presented a low NT-proBNP value and a relatively high GDF-15., Conclusions: Distinctive characteristics of biomarkers in HFpEF phenotypes would indicate differential underlying mechanisms to be elucidated. The contribution of inflammation to the pathogenesis varied considerably among different HFpEF phenotypes. Systemic inflammation substantially contributes to the pathophysiology of the classic HFpEF phenotype with cardiac hypertrophy., Trial Registration Number: UMIN-CTR ID: UMIN000021831., Competing Interests: Competing interests: YSo has received grants from Roche Diagnostics, FUJIFILM Toyama Chemical, TOA EIYO, Bristol-Myers Squibb, Biosense Webster, Abbott Medical Japan and NIPRO; and personal fees from Abiomed, AstraZeneca, Amgen Astellas BioPharma, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Abbott Medical Japan, Boston Scientific Japan, Bayer, Daiichi Sankyo, Novartis, TERUMO, Medtronic and Pfizer Pharmaceuticals. SH has received grants from Roche Diagnostics, FUJIFILM Toyama Chemical and Actelion Pharmaceuticals; and personal fees from Daiichi Sankyo, Astellas Pharma, Bayer, Pfizer Pharmaceuticals, Boehringer Ingelheim Japan, Kowa Company and Ono Pharmaceutical. DN has received personal fees from Roche Diagnostics. YSa has received personal fees from Otsuka Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, AstraZeneca and Actelion Pharmaceuticals; and grants from Roche Diagnostic, FUJIFILM Toyama Chemical, Bristol-Myers Squibb Co, Biosense Webster, Abbott Medical Japan, Otsuka Pharmaceutical, Daiichi Sankyo Company, Mitsubishi Tanabe Pharma Corporation, Astellas Pharma, Kowa Company, Boehringer Ingelheim Japan and Biotronik., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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 < 0.0124, recurrence of AF did not significantly differ between PVI-plus and PVI-alone (HR 1.17; 95% CI 0.57-2.39; P-value = 0.661). By employing uplift modeling, we could effectively identify a subset of patients with persistent AF who would benefit from PVI-plus. This model could be valuable in stratifying patients with persistent AF who need extensive catheter ablation before the procedure., (© 2024. The Author(s).)

Aim: Both recurrent myocardial infarction (ReMI) and bleeding events after acute myocardial infarction (AMI) were reportedly associated with increased mortality. To date, the prognostic impact of these events on subsequent outcomes in East Asians is still unclear. In this study, we aimed to investigate the impact of bleeding or thrombotic events during acute phase on subsequent mortality and time-dependent change of the impact in patients with AMI undergoing percutaneous coronary intervention (PCI)., Method: We conducted a prospective, multicenter, observational study of patients with AMI (n=12,093). The patients who did not undergo emergent PCI were excluded. In addition, the patients registered before 2003 were excluded because the data of bleeding severity was not obtained. Eligible patients were divided into two groups based on the occurrence of major bleeding within 7 days of PCI, and the same approach was performed for ReMI within 7 days of PCI. The endpoint of this study was all-cause death. We assessed the impact of major bleeding and ReMI, which occurred within 7 days of index PCI, on the subsequent clinical outcomes up to 5 years., Results: A total of 6,769 patients were found to be eligible. All-cause death occurred in 898 (13.3%) patients during a median follow-up period of 1,726 [511-1,840] days. After adjustment for multiple confounders, major bleeding in 7 days from index PCI was independently associated with higher 30-day and 30-day to 1-year mortality (odds ratio [OR]: 2.06 [1.45-2.92] p＜0.001, OR: 2.03 [1.28-3.15] p=0.002), whereas ReMI was not (OR: 1.93 [0.92-3.80] p=0.07, OR: 0.81 [0.24-2.03] p=0.68). Major bleeding and ReMI did not affect mortality between 1 and 5 years (hazard ratio [HR]: 1.32 [0.77-2.26] p=0.31, HR: 0.48 [0.12-1.94] p=0.30)., Conclusion: Major bleeding in 7 days from admission was independently associated with higher 30-day and 1-year mortality but not during 1-5 years. ReMI did not affect mortality in all phases. We should be more concerned about bleeding event during acute phase after PCI.

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., (© 2024. The Author(s).)

Background: Even with intracoronary imaging-guided stent optimisation, suboptimal haemodynamic outcomes post-percutaneous coronary intervention (PCI) can be related to residual lesions in non-stented segments. Preprocedural assessment of pathophysiological coronary artery disease (CAD) patterns could help predict the physiological response to PCI., Aims: The aim of this study was to assess the relationship between preprocedural pathophysiological haemodynamic patterns and intracoronary imaging findings, as well as their association with physiological outcomes immediately post-PCI., Methods: Data from 206 patients with chronic coronary syndrome enrolled in the ASET-JAPAN study were analysed. Pathophysiological CAD patterns were characterised using Murray law-based quantitative flow ratio (μQFR)-derived indices acquired from pre-PCI angiograms. The diffuseness of CAD was defined by the pullback pressure gradient (PPG) index. Intracoronary imaging in stented segments after stent optimisation was also analysed., Results: In the multivariable analysis, diffuse disease - defined by the pre-PCI μQFR-PPG index - was an independent factor for predicting a post-PCI μQFR <0.91 (per 0.1 decrease of PPG index, odds ratio 1.57, 95% confidence interval: 1.07-2.34; p=0.022), whereas the stent expansion index (EI) was not associated with a suboptimal post-PCI μQFR. Among vessels with an EI ≥80% and post-PCI μQFR <0.91, 84.0% of those vessels had a diffuse pattern preprocedure. There was no significant difference in EI between vessels with diffuse disease and those with focal disease. The average plaque burden in the stented segment was significantly larger in vessels with a preprocedural diffuse CAD pattern., Conclusions: A physiological diffuse pattern preprocedure was an independent factor in predicting unfavourable immediate haemodynamic outcomes post-PCI, even after stent optimisation using intracoronary imaging. Preprocedural assessment of CAD patterns could identify patients who are likely to exhibit superior immediate haemodynamic outcomes following PCI.

It is unclear whether adaptive servo-ventilation (ASV) therapy for heart failure with preserved ejection fraction (HFpEF) is effective. The aim of this study was to investigate the details of ASV use, and to evaluate the effectiveness and safety of ASV in real-world HFpEF patients. We retrospectively enrolled 36 HFpEF patients at nine cardiovascular centers who initiated ASV therapy during hospitalization or on outpatient basis and were able to continue using it at home from 2012 to 2017 and survived for at least one year thereafter. The number of hospitalizations for heart failure (HF) during the 12 months before and 12 months after introduction of ASV at home was compared. The median number of HF hospitalizations for each patient was significantly reduced from 1 [interquartile range: 1-2] in the 12 months before introduction of ASV to 0 [0-0] in the 12 months after introduction of ASV (p < 0.001). In subgroup analysis, reduction in heart failure hospitalization was significantly greater in female patients, patients with a body mass index < 25, and those with moderate or severe tricuspid valve regurgitation. In patients with HFpEF, the number of HF hospitalizations was significantly decreased after the introduction of ASV. HFpEF patients with female sex, BMI < 25, or moderate to severe tricuspid valve regurgitation are potential candidates who might benefit from ASV therapy., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

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 <0.0001). Conclusions Left atrial ablation in addition to PVI was efficacious during 3-year follow-up. Linear ablation was superior to other ablation strategies but may increase iatrogenic ATs. Registration URL: http://www.umin.ac.jp/ctr/index-j.htm; Unique identifier: UMIN000019449.

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., (© 2023. Springer Nature Limited.)

Objective: Our previously established machine learning-based clustering model classified heart failure with preserved ejection fraction (HFpEF) into four distinct phenotypes. Given the heterogeneous pathophysiology of HFpEF, specific medications may have favourable effects in specific phenotypes of HFpEF. We aimed to assess effectiveness of medications on clinical outcomes of the four phenotypes using a real-world HFpEF registry dataset., Methods: This study is a posthoc analysis of the PURSUIT-HFpEF registry, a prospective, multicentre, observational study. We evaluated the clinical effectiveness of the following four types of postdischarge medication in the four different phenotypes: angiotensin-converting enzyme inhibitors (ACEi) or angiotensin-receptor blockers (ARB), beta blockers, mineralocorticoid-receptor antagonists (MRA) and statins. The primary endpoint of this study was a composite of all-cause death and heart failure hospitalisation., Results: Of 1231 patients, 1100 (83 (IQR 77, 87) years, 604 females) were eligible for analysis. Median follow-up duration was 734 (398, 1108) days. The primary endpoint occurred in 528 patients (48.0%). Cox proportional hazard models with inverse-probability-of-treatment weighting showed the following significant effectiveness of medication on the primary endpoint: MRA for phenotype 2 (weighted HR (wHR) 0.40, 95% CI 0.21 to 0.75, p=0.005); ACEi or ARB for phenotype 3 (wHR 0.66 0.48 to 0.92, p=0.014) and statin therapy for phenotype 3 (wHR 0.43 (0.21 to 0.88), p=0.020). No other medications had significant treatment effects in the four phenotypes., Conclusions: Machine learning-based clustering may have the potential to identify populations in which specific medications may be effective. This study suggests the effectiveness of MRA, ACEi or ARB and statin for specific phenotypes of HFpEF., Trial Registration Number: UMIN000021831., Competing Interests: Competing interests: SH has received grants from Roche Diagnostics, FUJIFILM Toyama Chemical and Actelion Pharmaceuticals; and personal fees from Daiichi Sankyo, Astellas Pharma, Bayer, Pfizer Pharmaceuticals, Boehringer Ingelheim Japan, Kowa Company and Ono Pharmaceutical. DN has received personal fees from Roche Diagnostics. TK has received honoraria from AstraZeneca. YS has received personal fees from Otsuka Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, AstraZeneca K.K. and Actelion Pharmaceuticals, and grants from Roche Diagnostic, FUJIFILM Toyama Chemical, Bristol-Myers Squibb, Co, Biosense Webster, Inc., Abbott Medical Japan, Otsuka Pharmaceutical, Daiichi Sankyo Company, Mitsubishi Tanabe Pharma Corporation, Astellas Pharma, Kowa Company, Boehringer Ingelheim Japan, and Biotronik. The other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Backgrounds: Drug treatments of heart failure with preserved ejection fraction (HFpEF) have a little clinical benefit, but cardiovascular polypharmacy (CP) trend is observed in elderly HFpEF. We investigated the impact of CP on octogenarian with HFpEF., Methods: We examined 783 consecutive octogenarians (≥80 years) enrolled in the PURSUIT-HFpEF registry. We defined medications for hypertension, dyslipidemia, heart failure (HF), coronary artery disease, stroke, peripheral artery disease, and atrial fibrillation as cardiovascular medications (CM). In this study, we defined CP as ≥5 CM. We investigated whether CP was correlated with the composite end point (CE) of all-cause mortality and HF rehospitalization., Results: The proportion with CP was 51.9% (n = 406). Background characteristics correlated with CP were frailty, history of coronary artery disease, atrial fibrillation and left atrial dimension. Multivariable Cox proportional hazards analysis showed CP was significantly and independently correlated with CE (hazard ratio (HR): 1.31; 95% confidence Interval (CI): 1.01-1.70) in addition to age, clinical frailty scale, history of HF admission and N-terminal pro brain natriuretic peptide. Kaplan-Meier curve analysis showed that, compared with the non-CP group, the CP group had significantly higher risk of CE and HF (HR: 1.27; 95%CI: 1.04-1.56; P = 0.02 and HR: 1.46; 95%CI: 1.13-1.88; P < 0.01, respectively), but not any-cause death. In addition, diuretics were correlated with CE (HR: 1.61; 95%CI: 1.17-2.22; P < 0.01), but antithrombotic drugs and HFpEF medications were not., Conclusions: CP at discharge is a prognostic factor driven by HF rehospitalization in octogenarians with HFpEF. In these patients, diuretics may be correlated with the prognosis., Competing Interests: Declaration of Competing Interest Daisaku Nakatani has received honoraria from Roche Diagnostics. Shungo Hikoso has received personal fees from Daiichi Sankyo Company, Bayer, Astellas Pharma, Pfizer Pharmaceuticals and Boehringer Ingelheim Japan, and grants from Roche Diagnostics, FUJIFILM Toyama Chemical and Actelion Pharmaceuticals. Yasushi Sakata has received personal fees from Otsuka Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo Company, Mitsubishi Tanabe Pharma Corporation and Actelion Pharmaceuticals, and grants from Roche Diagnostic, FUJIFILM Toyama Chemical, Abbott Medical Japan, Otsuka Pharmaceutical, Daiichi Sankyo Company, Mitsubishi Tanabe Pharma Corporation and Biotronik. The other authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The vessel healing process after implantation of biodegradable polymer (BP) and durable polymer (DP) everolimus-eluting stent (EES) in ST-elevation myocardial infarction (STEMI) lesions remains unclear., Methods and results: We conducted a multicenter prospective randomized controlled trial to compare early (2 weeks) and mid-term (12 months) vascular responses after implantation of BP-EES vs. DP-EES in STEMI patients. In this prespecified subanalysis, serial coronary angioscopy (CAS) analysis was performed in 15 stents in the BP-EES arm (n=10 patients) and 14 stents in the DP-EES arm (n=10 patients). At the 2-week follow-up, there was no significant difference in the estimated marginal means of the neointimal coverage grade (primary endpoint) between the 2 arms (mean [±SE] 0.00±0.00 in both arms; P>0.999). There were no significant differences between the BP-EES and DP-EES groups in the yellow color grade (1.046±0.106 vs. 0.844±0.114, respectively; P=0.201) or the presence of thrombus (77.8% vs. 88.8%, respectively; P=0.205). At 12 months, competent strut coverage, defined as yellow color grade ≤1, no thrombus, and a neointimal coverage grade ≥1 was achieved more frequently in the BP-EES than DP-EES arm (85.2% vs. 53.1%; adjusted odds ratio 2.11 [95% confidence interval 1.26-3.53]; P=0.023)., Conclusions: Neointimal coverage 2 weeks after implantation of BP-EES and DP-EES in STEMI lesions was comparable on CAS evaluation. However, at 1 year, BP-EES was independently associated with competent strut coverage.

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 < 0.001). Cox multivariable analysis revealed that patients with EQ-5D-5L index in the low and middle tertiles had a significantly greater risk of mortality than those with EQ-5D-5L index in the high tertile [low EQ-5D-5L: adjusted hazard ratio (HR): 1.81 (1.12-2.92), P = 0.002, middle EQ-5D-5L: adjusted HR 1.91 (1.21-3.03), P = 0.006]. Among the dimensions of EQ-5D-5L, mobility (P = 0.014), self-care (P = 0.023) and usual activities (P = 0.008) were significant factors associated with all-cause mortality after multivariable adjustment., Conclusions: EQ-5D-5L is useful tool for risk stratification in patients with HFpEF., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Y. Sotomi received research grants from Abbott Medical Japan and TOA EIYO, and speaker honoraria from Abbott Medical Japan, Boston Scientific Japan, TERUMO, Japan Lifeline, Biosensors, Medtronic, Daiichi-Sankyo, Bayer, Boehringer Ingelheim, and Bristol Myers Squibb, and is an endowed chair funded by TOA EIYO. H. Mizuno is an endowed chair funded by TERUMO, Asahi Intecc, NIPRO, and Shimadzu Corporation, and received personal fees from Medtronic Japan, Japan Lifeline, and Abbott Medical Japan. Y. Sakata received grants form Abbott Medical Japan and Biotronik. The other authors have nothing to disclose., (© 2023 The Authors.)

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.

Background: We recently reported that nearly half of patients with heart failure with preserved ejection fraction (HFpEF) did not show echocardiographic diastolic dysfunction (DD), but had normal diastolic function (ND) or indeterminate diastolic function (ID). However, the clinical course and outcomes of patients with HFpEF with ND or ID (ND/ID) remain unknown., Methods: From the PURSUIT-HFpEF registry, we extracted 289 patients with HFpEF with ND/ID at discharge who had echocardiographic data at 1-year follow-up. Patients were classified according to the status of progression from ND/ID to DD at 1 year. Primary endpoint was a composite of all-cause death or HF rehospitalization., Results: Median age was 81 years, and 138 (47.8%) patients were female. At 1 year, 107 (37%) patients had progressed to DD. The composite endpoint occurred in 90 (31.1%) patients. Compared to patients without progression to DD, those with progression had a significantly higher cumulative rate of the composite endpoint (P < 0.001) and HF rehospitalization (P < 0.001) after discharge and at the 1-year landmark (P = 0.030 and P = 0.001, respectively). Progression to DD was independently associated with the composite endpoint (hazard ratio (HR): 2.014, 95%CI 1.239-3.273, P = 0.005) and HF rehospitalization (HR: 2.362, 95%CI 1.402-3.978) after discharge. Age (odds ratio (OR): 1.043, 95%CI 1.004-1.083, P = 0.031), body mass index (BMI) (OR: 1.110, 95%CI 1.031-1.195, P = 0.006), and albumin (OR: 0.452, 95%CI 0.211-0.969, P = 0.041) were independently associated with progression from ND/ID to DD., Conclusions: More than one-third of HFpEF patients with ND/ID progressed to DD at 1 year and had poor outcomes. Age, BMI and albumin were independently associated with this progression., Umin-Ctr Id: UMIN000021831., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Two key echocardiographic parameters, left ventricular mass index (LVMI) and left atrial volume index (LAVI), are important in assessing structural myocardial changes in heart failure (HF) with preserved ejection fraction (HFpEF). However, the differences in clinical characteristics and outcomes among groups classified by LVMI and LAVI values are unclear.We examined the data of 960 patients with HFpEF hospitalized due to acute decompensated HF from the PURSUIT-HFpEF registry, a prospective, multicenter observational study. Four groups were classified according to the cut-off values of LVMI and LAVI [LVMI = 95 g/m 2 (female), 115 g/m 2 (male) and LAVI = 34 mL/m 2 ]. Clinical endpoints were the composite of HF readmission and all-cause death. Study endpoints among the 4 groups were evaluated. The composite endpoint occurred in 364 patients (37.9%). Median follow-up duration was 445 days. Kaplan-Meier analysis revealed significant differences in the composite endpoint among the 4 groups (P < 0.001). Cox proportional hazards analysis demonstrated that patients with increased LAVI alone were at significantly higher risk of HF readmission and the composite endpoints than those with increased LVMI alone (P = 0.030 and P = 0.024, respectively). Age, male gender, systolic blood pressure at discharge, atrial fibrillation (AF) hemoglobin, renal function, and LAVI were significant determinants of LVMI and female gender, AF, hemoglobin, and LVMI were significant determinants of LAVI.In HFpEF patients, increased LAVI alone was more strongly associated with HF readmission and the composite of HF readmission and all-cause death than those with increased LVMI alone.

To investigate the difference in the prognostic impact of loop diuretics in patients with acute myocardial infarction (AMI) based on plasma volume status, a total of 3,364 survivors of AMI who were registered in the large database of the Osaka Acute Coronary Insufficiency Study (OACIS) were studied. Plasma volume status was assessed by the estimated plasma volume status (ePVS) that was calculated based on a weight- and hematocrit-based formula at discharge. The endpoint was a composite endpoint of all-cause death and rehospitalization due to heart failure for 5 years. During a median follow-up period of 1.9 years, 90 and 223 patients had events in the groups with low ePVS (

Background: Although embolic stroke accounts for most cerebral infarction, examinations to identify the embolic source have been insufficient. Nonobstructive general angioscopy (NOGA) has developed to allow the detailed observation of atheromatous changes of the aorta., Objectives: The purpose of this study was to clarify the importance of the aortogenic mechanism in the development of ischemic stroke., Methods: We examined 114 consecutive patients whose aorta was observed by NOGA and who subsequently underwent brain magnetic resonance imaging to detect ischemic stroke lesions. In the evaluation of the aorta, the presence and location of spontaneously ruptured aortic plaque (SRAP) were determined. The aorta was observed from the origin to the arch (proximal aorta [PAo]) and the proximal descending aorta., Results: Forty-nine of 114 patients had SRAP observed by NOGA. Among these, 24 had SRAP in the PAo, and 43 had SRAP in the descending aorta. Thirty-three patients had ischemic stroke lesions, including 6 with a clinical neurologic deficit. The frequency at which SRAP was detected in these patients was significantly higher in comparison to 81 patients without ischemic stroke (69% vs 33%; P  < 0.01). The sensitivity and specificity of the presence of SRAP for ischemic stroke were 0.70 and 0.68, respectively. The presence of SRAP in PAo was significantly correlated with ischemic stroke (odds ratio: 14.3; P  < 0.001)., Conclusions: In the treatment of ischemic stroke, attention should be paid to SRAP, especially that in the PAo. (STROKE-NOGA [SponTaneously Ruptured aOrtic plaques as a potential cause of embolic stroKEs visualized by Non-Obstructive General Angioscopy] Study; UMIN000034588)., Competing Interests: Dr Komatsu is a technical consultant for Nemoto Kyorin-do Co. Ltd. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

The impact of changes in nutritional status during hospitalization on prognosis in patients with heart failure with preserved ejection fraction (HFpEF) remains unknown. We examined the association between changes in the Geriatric Nutritional Risk Index (GNRI) and prognosis during hospitalization in patients with HFpEF stratified by nutritional status on admission. Nutritional status did and did not worsen in 348 and 349 of 697 patients with high GNRI on admission, and in 142 and 143 of 285 patients with low GNRI on admission, respectively. Kaplan-Meier analysis revealed no difference in risk of the composite endpoint, all-cause death, or heart failure admission between patients with high GNRI on admission whose nutritional status did and did not worsen. In contrast, patients with low GNRI on admission whose nutritional status did not worsen had a significantly lower risk of the composite endpoint and all-cause death than those who did. Multivariable analysis revealed that worsening nutritional status was independently associated with a higher risk of the composite endpoint and all-cause mortality in patients with low GNRI on admission. Changes in nutritional status during hospitalization were thus associated with prognosis in patients with malnutrition on admission, but not in patients without malnutrition among those with HFpEF.

Objective: We aim to clarify the differences in the association between re-admission for heart failure (HF) and left atrial (LA) overload indices by sex in heart failure and a preserved ejection fraction (HFpEF)., Methods: We analyzed 898 HFpEF patients hospitalized for acute decompensated HF. Blood tests and transthoracic echocardiography were performed before discharge. The primary endpoint was re-admission for HF during the first year., Results: The ratio of diastolic elastance to arterial elastance ( p = 0.014), a relative index of LA pressure overload, in men and LA volume index (LAVI, p = 0.020) in women were significant for re-admission for HF during the first year in the multivariable Fine-Gray analysis. Stroke volume (SV)/LA volume (LAV), another index for LAV overload, was not a significant prognostic factor of re-admission for HF during this time., Conclusion: LA overload was an important prognostic factor for HF re-readmission during the first year after enrolment in patients with HFpEF, but the indices relating to LA overload differed by sex.

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.