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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.

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

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.

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

Abstract Aims Heart failure (HF) is reported to be one of the major risks of bleeding events. On the other hand, HF patients frequently receive anticoagulants or antiplatelet therapy to manage various co‐morbidities. However, predictors of bleeding events in patients with HF have rarely been reported. This study aimed to evaluate the predictors of bleeding events and relationship between bleeding events and HF re‐hospitalizations. Methods and results We included 1660 acute decompensated heart failure (ADHF) patients from the AURORA registry between January 2015 and December 2020. A total of 1429 patients were excluded because of history of HF admission, missing echocardiographic data at discharge, lost to follow‐up, haemodialysis and no antithrombotic drugs. Finally, we evaluated 231 patients from AURORA registry. The bleeding events were defined as Type 2 to 5 bleeding according to the Bleeding Academic Research Consortium definition. We divided our patients into the bleeding group and non‐bleeding group. We compared the baseline characteristics, medications, laboratory data, and echocardiographic data between the two groups. Median age was 78 (IQR 71–82) years old and male accounted for 59%. Approximately half of the patients had an antiplatelet therapy and 70% had an anticoagulant therapy. During a median follow‐up of 651 (IQR 357–1139) days, 32 patients (13.8%) suffered from bleeding events. The major driver of the registered events was gastrointestinal bleeding (n = 21, 65.6%), and the other events were cerebral bleeding (n = 4, 12.5%), intraarticular bleeding (n = 2, 6.3%), urogenital bleeding (n = 2, 6.3%), haemorrhagic pericardial effusions (n = 1, 3.1%), subcutaneous hematomas (n = 1, 3.1%), and haemothorax (n = 1, 3.1%). There was a significantly lower haemoglobin level (P

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.

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.

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.

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

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.

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.

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

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.

Abstract Aims The impacts of high density lipoprotein cholesterol (HDL‐C) as an anti‐inflammatory and C reactive protein (CRP) as inflammatory properties on the pathogenesis of heart failure were reported. At present, the clinical significance of the HDL‐C/CRP ratio in heart failure with preserved ejection fraction (HFpEF) patients remains unknown. Methods and results We examined the data on 796 consecutive 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 calculated the HDL/CRP ratios and evaluated the relationship between the values and clinical outcomes, including degree of cardiac function. The mean follow‐up duration was 420 ± 346 days. All‐cause death occurred in 118 patients, of which 51 were cardiac deaths. HDL/CRP ≤ 4.05 was independently and significantly associated with all‐cause death (odds ratio = 1.84, 95% CI: 1.06–3.20, P = 0.023), and HDL/CRP ≤ 3.14 was associated with cardiac death by multivariate Cox proportional hazard analysis (odds ratio = 2.86, 95% CI: 1.36–6.01, P = 0.003). HDL‐C/CRP ratio significantly correlated with the product of the left atrial volume and left ventricular mass index as well as the tricuspid annular plane systolic excursion by multiple regression analysis (standardized beta‐coefficient = −0.085, P = 0.034 and standardized beta‐coefficient = 0.081, P = 0.044, respectively). Conclusions HDL‐C/CRP ratio was a useful marker for predicting all‐cause death and cardiac death and correlated with left ventricular diastolic function and right ventricular systolic function in HFpEF patients.

Abstract Aims The prognostic importance of admission systolic blood pressure (SBP) in heart failure with preserved ejection fraction (HFpEF) is elusive. We aimed to clarify the pathophysiological differences between patients categorized with admission SBP among HFpEF patients. Methods and results We studied 1008 inpatients from PURSUIT‐HFpEF, a multicentre prospective observational registry. We classified patients as having elevated (>140 mmHg), preserved (90–140 mmHg), or low (

Background Although potential therapeutic candidates for heart failure with preserved ejection fraction (HFpEF) are emerging, it is still unclear whether they will be effective in patients with left ventricular ejection fraction (LVEF) of 60% or higher. Our aim was to identify the clinical characteristics of these patients with HFpEF by comparing them to patients with LVEF below 60%. Methods and Results From a multicenter, prospective, observational cohort (PURSUIT‐HFpEF [Prospective Multicenter Obsevational Study of Patients with Heart Failure with Preserved Ejection Fraction]), we investigated 812 consecutive patients (median age, 83 years; 57% women), including 316 with 50% ≤ LVEF

Objectives The prognostic significance of an afterload-integrated diastolic index, the ratio of diastolic elastance (Ed) to arterial elastance (Ea) (Ed/Ea=[E/e′]/[0.9×systolic blood pressure]), is valid for 1 year after discharge in older patients with heart failure with preserved ejection fraction (HFpEF). We aimed to clarify the association with changes in Ed/Ea from enrolment to 1 year and prognosis thereafter in patients with HFpEF.Setting A prospective, multicentre observational registry of collaborating hospitals in Osaka, Japan.Participants We enrolled 659 patients with HFpEF hospitalised for acute decompensated heart failure (men/women: 296/363). Blood tests and transthoracic echocardiography were performed before discharge and at 1 year after.Primary outcome measures All-cause mortality and/or re-admission for heart failure were evaluated after discharge.Results High Ed/Ea assessed before discharge was a significant prognostic factor during the first, but not the second, year after discharge in all-cause mortality or all-cause mortality and/or re-admission for heart failure. When re-analysis was performed using the value of Ed/Ea at 1 year after discharge, high Ed/Ea was significant for the prognosis during the second year for both end points (p=0.012 and p=0.033, respectively). The poorest mortality during 1‒2 years after enrolment was observed in those who showed a worsening Ed/Ea during the first year associated with larger left ventricular mass index and reduced left ventricular ejection fraction. In all-cause mortality and/or re-admission for heart failure, the event rate during 1‒2 years was highest in those with persistently high Ed/Ea even after 1 year.Conclusions Time-sensitive prognostic performance of Ed/Ea, an afterload-integrated diastolic index, was observed in older patients with HFpEF.Trial registration number UMIN000021831.

Abstract Background Complicated pathophysiology makes it difficult to identify the prognosis of heart failure with preserved ejection fraction (HFpEF). While plasma osmolality has been reported to have prognostic importance, mainly in heart failure with reduced ejection fraction (HFrEF), its prognostic meaning for HFpEF has not been elucidated. Methods We prospectively studied 960 patients in PURSUIT-HFpEF, a multicenter observational study of acute decompensated HFpEF inpatients. We divided patients into three groups according to the quantile values of plasma osmolality on admission. During a follow-up averaging 366 days, we examined the primary composite endpoint of cardiac mortality or heart failure re-admission using Kaplan–Meier curve analysis and Cox proportional hazard testing. Results 216 (22.5%) patients reached the primary endpoint. Kaplan–Meier curve analysis revealed that the highest quantile of plasma osmolality on admission (higher than 300.3 mOsm/kg) was significantly associated with adverse outcomes (Log-rank P = 0.0095). Univariable analysis in the Cox proportional hazard model also revealed significantly higher rates of adverse outcomes in the higher plasma osmolality on admission (hazard ratio [HR] 7.29; 95% confidence interval [CI] 2.25–23.92, P = 0.0009). Multivariable analysis in the Cox proportional hazard model also showed that higher plasma osmolality on admission was significantly associated with adverse outcomes (HR 5.47; 95% CI 1.46–21.56, P = 0.0113) independently from other confounding factors such as age, gender, comorbid of atrial fibrillation, hypertension history, diabetes, anemia, malnutrition, E/e′, and N-terminal pro-B-type natriuretic peptide elevation. Conclusions Higher plasma osmolality on admission was prognostically important for acute decompensated HFpEF inpatients.

Abstract Aims The HFA‐PEFF score is a part of the stepwise diagnostic algorithm of heart failure with preserved ejection fraction (HFpEF). We aimed to evaluate the prognostic significance of the HFA‐PEFF score on the clinical outcomes in patients with HFpEF. Methods and results The Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with preserved Ejection Fraction (PURSUIT‐HFpEF) study is a prospective, multicentre, observational study in which collaborating hospitals in Osaka record clinical, echocardiographic, and outcome data of patients with acute decompensated heart failure with preserved left ventricular ejection fraction (≥50%) [UMIN‐CTR ID: UMIN000021831]. Acute decompensated heart failure was diagnosed on the basis of the following criteria: (i) clinical symptoms and signs according to the Framingham Heart Study criteria; and (ii) serum N‐terminal pro‐B‐type natriuretic peptide level of ≥400 pg/mL or brain natriuretic peptide level of ≥100 pg/mL. The HFA‐PEFF score has functional, morphological, and biomarker domains. We evaluated the prognostic significance of the HFA‐PEFF score (calculated based on the data at hospital discharge) on post‐discharge clinical outcomes in this cohort. The primary endpoint of the present study was a composite of all‐cause death and heart failure readmission. Between June 2016 and December 2019, 871 patients were enrolled from 26 hospitals (mean follow‐up duration 399 ± 349 days). A total of 804 patients were finally analysed after excluding patients with scores of 0 (N = 5) and 1 (N = 15) from 824 patients with available HFA‐PEFF score based on the echocardiographic and laboratory data at discharge. According to the laboratory and echocardiographic data at the time of discharge, 487 patients (59.1%) were diagnosed as HFpEF (HFA‐PEFF score ≥ 5) while 317 patients (38.5%) had intermediate score. Kaplan–Meier analysis divided by the HFA‐PEFF score [low, score 2–5 (N = 494) vs. high, score 6 (N = 310)] indicated that the HFA‐PEFF score successfully stratified the patients for the primary endpoint (log‐rank test P

Abstract Aims Heart failure (HF) readmissions with preserved ejection fraction (HFpEF) are increasing in the elderly, which is a major socioeconomic problem. We investigated the clinical impact of HF readmissions (HFR) on octogenarians with HFpEF. Methods and results We enrolled consecutive octogenarians (≥80 years old) from June 2016 to February 2020 in PURSUIT‐HFpEF registry. We divided them into HFR group readmitted for HF during the follow‐up period and non‐HF readmission (non‐HFR) group. We evaluated the impact of HFR on all‐cause mortality, cardiac death, and quality of life (QOL). Additionally, we evaluated the factors at discharge correlated with HFR. HFR group comprised 116 patients (21.4%). Among all‐cause deaths, 40 patients suffered cardiac deaths (48.2%). The Kaplan–Meier analysis revealed a similar prognosis between HFR and non‐HFR groups as well as similar incidences of HF deaths. The QOL scores had significantly deteriorated by 1 year later in the HFR group (0.71 ± 0.19 vs. 0.59 ± 0.21, P

Background: Right ventricular (RV)-pulmonary artery (PA) uncoupling is associated with poor outcomes in heart failure patients. We aimed to elucidate the relationship between RV-PA uncoupling and late arrhythmia recurrence after ablation in persistent atrial fibrillation (PerAF) patients whose phenotypes have impaired right ventricular function and pulmonary hypertension. Methods: The present study included 203 PerAF patients from the Osaka Rosai Atrial Fibrillation ablation (ORAF) registry who underwent an initial ablation. We assigned the patients based on the value of tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio that could predict late recurrence of AF/atrial tachycardia (LRAF) as an indicator of RV-PA uncoupling. We evaluated the following factors: the difference in the relationship between TASPE/PASP before ablation and incidence of LRAF among the 2 groups stratified by TAPSE/PASP based on the above cut-off value and TAPSE/PASP change from before to one-year after ablation. Results: A receiver operating characteristic curve analysis revealed a good accuracy of predicting LRAF by TAPSE/PASP ratio with a cutoff of 0.57. The patients with TAPSE/PASP ratios ≤ 0.57 had a significantly greater LRAF risk than TAPSE/PASP ratios > 0.57. A multivariate Cox proportional hazards analysis showed that TAPSE/PASP (HR 0.12, 95% CI; 0.019–0.724, p = 0.026) was independently and significantly associated with LRAF. The TAPSE/PASP significantly improved more one-year after the ablation than before (p = 0.016). Conclusion: RV-PA uncoupling was independently associated with LRAF, independent of left atrial function, and significantly improved more one-year after the ablation than before in PerAF patients.

Abstract Background and Aims There are two types of serum uric acid‐lowering agents, the xanthine oxidoreductase (XO) inhibitor and non‐XO inhibitor. We investigated whether febuxostat, XO inhibitor, could produce more favorable effects on coronary endothelial function (CEF) and renal function than benzbromarone, non‐XO inhibitor, in hyperuricemic coronary artery disease (CAD) patients. Methods We divided 21 hyperuricemic patients with stenting for left anterior descending (LAD) or left circumflex (LCX) artery into patients started on febuxostat (F group) and those on benzbromarone (B group). After 8 months, all patients underwent CEF evaluations (acetylcholine provocation test) and optical coherence tomography (OCT) for non‐culprit vessels (e.g. if patients received LAD stenting, we evaluated LCX). We compared the diameter ratio induced by acetylcholine and baseline (CEF ratio), thin‐cap fibroatheroma and calcified plaque by OCT, uric acid, oxidative stress biomarkers, and renal function including estimated glomerular filtration rate (eGFR) between F and B groups. Creatinine 2 days after stenting was measured to evaluate contrast‐induced nephropathy (CIN). Results Change of eGFR was significantly lower in F group (n= 11) than B group over 8 months while the other parameters including CEF ratio were similar. F group showed favorable effects for CIN. Conclusion In conclusion, 8‐months of febuxostat, XO inhibitor, does not significantly protect CEF but can protect the renal function including CIN in hyperuricemic patients with CAD compared to benzbromarone, non‐XO inhibitor.

BackgroundThe detailed electrophysiological characteristics of atrial fibrillation (AF) initiating non-pulmonary vein (PV) triggers excluding origins from the superior vena cava (SVC) and left atrial posterior wall (LAPW) (Non-PV-SVC-LAPW triggers) remain unclear. This study aimed to clarify the detailed electrophysiological characteristics of non-PV-SVC-LAPW triggers.MethodsAmong 446 AF ablation procedures at 2 institutions, patients with reproducible AF initiating non-PV-SVC-LAPW triggers were retrospectively enrolled. The trigger origin was mapped using the self-reference mapping technique. The following electrophysiological parameters were evaluated: the voltage during sinus rhythm and at the onset of AF at the earliest activation site, coupling interval of the trigger between the prior sinus rhythm and AF trigger, and voltage change ratio defined as the trigger voltage at the onset of AF divided by the sinus voltage.ResultsDetailed electrophysiological data were obtained at 28 triggers in 21 patients. The median trigger voltage at the onset of AF was 0.16mV and median trigger coupling interval 182msec. Normal sinus voltages (≧0.5mV) were observed at 16 triggers and low voltages (ConclusionsThe trigger voltage at the onset of AF was low, regardless of whether the sinus voltage of the trigger was preserved or low.

Abstract Background Enlarged left atrium (LA) is an established predictor of recurrence of atrial fibrillation (AF) after pulmonary vein isolation (PVI), but occasionally recurrences of AF/atrial tachycardia (AT) are experienced in patients with normal left atrial diameter. Therefore, the predictors of AF recurrence and AF triggers were evaluated in patients with normal LA. Methods We enrolled 168 patients with normal LA (

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.

Abstract Aim The factors correlated with prognosis in heart failure with mid‐range ejection fraction (HFmrEF) is unclear, especially for acute heart failure (AHF) with HFmrEF. Thus, we investigated the factors correlated with the improvement in the ejection fraction (EF) over 1 year in AHF patients with HFmrEF. Methods and results In Acute Heart Failure Registry in the Osaka Rosai Hospital, we examined 159 consecutive HFmrEF patients out of 1051 HF patients who were admitted to our hospital for AHF from January 2015 to December 2017. We divided them into improved EF (IM) group whose EF improved (≧10%) and non‐IM group who had no improvement. We compared the baseline characteristics, echocardiographic data, medications, examinations for ischaemia, invasive treatments, and clinical outcomes between IM group and non‐IM group. IM group consisted of 21 patients (20%). IM group had a significantly more de novo heart failure, higher serum albumin (Alb), lower EF, smaller left ventricular dimension during diastole, more frequent coronary angiogram during hospitalization, and coronary intervention. Multivariate analysis revealed that Alb, left ventricular dimension during diastole, and coronary angiogram performed during hospitalization were independently associated with the improvement in the EF. In addition, IM group had less rehospitalizations over 1 year and a greater reduction in the B‐type natriuretic peptide level during the follow‐up than non‐IM group. Conclusions In AHF patients with HFmrEF, we should evaluate for any ischaemic heart disease during hospitalization, especially in patients with non‐enlarged left ventricular and non‐reduced serum Alb. AHF patients with HFmrEF who showed improvement in the EF tended to have better prognosis than those without improvement.

Background The female preponderance in heart failure with preserved ejection fraction (HFpEF) is a distinguishing feature of this disorder, but the association of sex with degree of diastolic dysfunction and clinical outcomes among individuals with HFpEF remains unclear. Methods and Results We conducted a prospective, multicenter, observational study of patients with HFpEF (PURSUIT‐HFpEF [Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction]: UMIN000021831). Between 2016 and 2019, 871 patients were enrolled from 26 hospitals (follow‐up: 399±349 days). We investigated sex‐related differences in diastolic dysfunction and postdischarge clinical outcomes in patients with HFpEF. The echocardiographic end point was diastolic dysfunction according to American Society of Echocardiography/European Association of Cardiovascular Imaging criteria. The clinical end point was a composite of all‐cause death and heart failure readmission. Women accounted for 55.2% (481 patients) of the overall cohort. Compared with men, women were older and had lower prevalence rates of hypertension, coronary artery disease, and chronic kidney disease. Women had diastolic dysfunction more frequently than men (52.8% versus 32.0%, P

Background: The neutrophil-to-lymphocyte ratio (NLR) has been proposed as an indicator of a systemic inflammatory response. There are baseline differences in the inflammation status between paroxysmal atrial fibrillation (PAF) and persistent AF (PerAF). The NLR changes and late recurrences of AF (LRAF) after ablation depending on the AF type remain unknown. Methods: Consecutive AF patients undergoing pulmonary vein isolation (PVI) by radiofrequency catheter ablation were enrolled from September 2014 to June 2018. The peripheral blood leukocyte NLR 1 day before and 36–48 h after PVI were measured. First, the relationship between NLR changes after to before ablation (ΔNLR) and ERAFs/LRAFs in PAF and PerAF patients were investigated to exclude the baseline inflammation status and evaluate catheter ablation induced inflammation. Second, the clinical impact of the NLR for predicting LRAFs was evaluated. Results: There hundred sixty-nine PAF and 264 PerAF patients from Osaka Rosai AF registry were enrolled. The ratio of ERAFs/LRAFs in PAF and PerAF patients were 26.8%/22.5% and 39.4%/29.9%, respectively. In PAF and PerAF patients, the ΔNLR was significantly higher with ERAF than no-ERAF (p = 0.022 and p = 0.010, respectively). In PAF patients, the ΔNLR was significantly higher with LRAF than no-LRAF (p = 0.017), while with PerAF, the ΔNLR did not significantly differ between LRAFs and no-LRAFs. In PAF, the ΔNLR was independently and significantly associated with LRAFs after PVI (p = 0.029). Conclusion: The ΔNLR was significantly higher only in PAF patients with LRAFs than no-LRAFs, but not in PerAF patients. The ΔNLR was useful for predicting LRAFs after PVI in PAF patients.

Objective During follow-up time, the value of prognostic factors may change, especially in the elderly patients, and the altered extent may affect the prognosis. We aimed to clarify the significance of the ratio of diastolic elastance (Ed) to arterial elastance (Ea), (Ed/Ea=(E/e’)/(0.9×systolic blood pressure)), an afterload-integrated diastolic index, in relation to follow-up periods and other laboratory factors, on the prognosis of elderly patients with heart failure with preserved ejection fraction (HFpEF).Methods We studied 552 HFpEF patients hospitalised for acute decompensated heart failure (men/women: 255/297). Blood testing and transthoracic echocardiography were performed before discharge. The primary endpoint was all-cause mortality.Results During a median follow-up of 508 days, 88 patients (men/women: 39/49) had all-cause mortality. During the first year after discharge, Ed/Ea (p=0.045) was an independent prognostic factor in association with albumin (p

(1) Background: It has been reported that tolvaptan (TLV) has a renoprotective effect in acute decompensated heart failure (ADHF) patients, but whether this effect is continued for a long time is unclear. Thus, we evaluated the time course of the renoprotective effect of TLV, in addition to the prognosis, in ADHF patients. (2) Methods: We investigated 911 ADHF patients from the AURORA (Acute Heart Failure Registry in Osaka Rosai Hospital) registry. After propensity score matching, 58 patients who started to receive TLV at least two days after the hospitalization (TLV group) and 58 who did not (non-TLV group) were examined. We compared the changes in the creatinine (Cr) and estimated glomerular filtration rate (eGFR) between baseline and each time point (five days, discharge, and one year) as the index of the renoprotective effect, and rate of rehospitalizations and all-cause mortality for one year between the two groups. (3) Results: The change in Cr and eGFR levels was significantly higher in the TLV group than the non-TLV group five days after admission but the difference between the two groups gradually diminished. A Kaplan–Meier analysis showed that the survival and rehospitalization rates in the TLV and non-TLV groups were similar up to one year. (4) TLV revealed a temporal change in the renoprotective effect, which may be correlated with no long-term beneficial effect of TLV.

INTRODUCTION: Recent epidemiological studies show that high intakes of carotenoids might be useful to maintain bone health, but little is known about the association of serum carotenoids with change of bone mineral density (BMD). The objective of this study was to investigate longitudinally whether serum carotenoids are associated with bone loss. METHODS: We conducted a follow-up on 146 male and 99 pre- and 212 post-menopausal female subjects from the Mikkabi study. Those who participated in previous BMD surveys and completed four years of follow-up were examined longitudinally. RESULTS: During a 4-year follow-up, 15 of the post-menopausal female subjects developed new-onset osteoporosis. In contrast, none of the male and pre-menopausal female subjects did. In male and pre-menopausal female subjects, the six serum carotenoids at the baseline were not associated with bone loss. On the other hand, in post-menopausal female subjects, the 4-year bone loss of radius was inversely associated with the serum carotenoid concentrations, especially in β-carotene. After adjustments for confounders, the odds ratios (OR) for osteoporosis in the highest tertiles of serum β-carotene and β-cryptoxanthin against the lowest tertiles were 0.24 (95% confidence interval 0.05-1.21) and 0.07 (CI: 0.01-0.88), respectively. Serum β-cryptoxanthin was also inversely associated with the risk for osteopenia and/or osteoporosis (P for trend, 0.037). In addition, our retrospective analysis revealed that subjects who developed osteoporosis and/or osteopenia during the survey period had significantly lower serum concentrations of β-cryptoxanthin and β-carotene at the baseline than those in the normal group. CONCLUSIONS: Antioxidant carotenoids, especially β-cryptoxanthin and β-carotene, are inversely associated with the change of radial BMD in post-menopausal female subjects.

This document provides supplemental material for a study on heart failure with preserved ejection fraction (HFpEF). It includes tables that present clinical characteristics and biomarker analysis of the patients included and excluded from the study, as well as the different phenotypes and their corresponding biomarker levels. The tables provide data on factors such as age, sex, blood pressure, comorbidities, and laboratory values. This information can be valuable for researchers studying heart failure and its subphenotypes. [Extracted from the article]