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Background Growth differentiation factor 15 (GDF15) is a cytokine responding to oxidative stress and inflammation, and it regulates appetite and energy balance. The association between GDF15 and clinical factors and its prognostic value in elderly multimorbid patients with heart failure with preserved ejection fraction (HFpEF) have not been well unknown.Methods This exploratory analysis is part of the Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with preserved Ejection Fraction study (N=1231), an ongoing, prospective, multicentre observational study of acute decompensated HFpEF (UMIN000021831). A predefined subcohort of 212 patients underwent multi-biomarker testing. Of these, we analysed 181 patients with available GDF15 data. The primary endpoint was a composite of all-cause death and hospitalisation for HF.Results In this analysis population, the median age was 81 (75–85) years, with 48% male patients. GDF15 significantly correlated with cardiac burden, anaemia, renal dysfunction and inflammation. Notably, poor nutritional status was significantly associated with GDF15. GDF15 was linked to poor prognosis in this elderly multimorbid cohort with HFpEF (adjusted HR for log-transformed GDF15: 13.67, 95% CI: 2.78 to 67.22, p=0.001). Furthermore, GDF15 added significant incremental value to the MAGGIC risk score (net reclassification improvement=0.4955 (95% CI: 0.1367 to 0.8543), p=0.007; integrated discrimination improvement=0.0278 (95% CI: 0.0013 to 0.0543), p=0.040).Conclusions GDF15 was associated with anaemia, inflammation, renal dysfunction, cardiac burden and malnutrition. It demonstrated prognostic value in elderly multimorbid HFpEF patients, suggesting its potential role as a complementary marker for the prognostic risk assessment of HFpEF patients.Trial registration number UMIN-CTR ID: UMIN000021831.

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.

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.

Objectives The severity of diastolic dysfunction is assessed using a combination of several indices of left atrial (LA) volume overload and LA pressure overload. We aimed to clarify which overload is more associated with the prognosis in patients with heart failure and preserved ejection fraction (HFpEF).Setting A prospective, multicenter observational registry of collaborating hospitals in Osaka, Japan.Participants We enrolled hospitalised patients with HFpEF showing sinus rhythm (men, 79; women, 113). Blood tests and transthoracic echocardiography were performed before discharge. The ratio of diastolic elastance (Ed) to arterial elastance (Ea) was used as a relative index of LA pressure overload.Primary outcome measures All-cause mortality and admission for heart failure were evaluated at >1 year after discharge.Results In the multivariable Cox regression analysis, Ed/Ea, but not LA volume index, was significantly associated with all-cause mortality or admission for heart failure (HR 2.034, 95% CI 1.059 to 3.907, p=0.032), independent of age, sex, and the serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level. In patients with a higher NT-proBNP level, the effect of higher Ed/Ea on prognosis was prominent (p=0.015).Conclusions Ed/Ea, an index of LA pressure overload, was significantly associated with the prognosis in elderly patients with HFpEF showing sinus rhythm.Trial registration number UMIN000021831.

Objective The semiquantitative urine dipstick test is a simple and convenient method that is available in the smallest community-based healthcare clinics. We sought to clarify the prognostic significance of dipstick proteinuria in patients with heart failure (HF) with preserved ejection fraction (HFpEF).Design A Prospective mUlticenteR obServational stUdy of patIenTs with Heart Failure with preserved Ejection Fraction (PURSUIT-HFpEF) registry.Participants and setting We assessed 851 discharged-alive patients in the PURSUIT-HFpEF registry who were initially hospitalised due to an acute decompensated HFpEF (EF≥50%) and elevated N-terminal-pro-brain natriuretic peptide (≥400 ng/L) at Osaka University Hospital and other 30 affiliated hospitals in the Kansai region of Japan. Patients received a urine dipstick test, and were divided into two groups according to the absence or presence of proteinuria. A trace or more of dipstick proteinuria was defined as the presence of proteinuria.Main outcome measures A composite of cardiac death or HF rehospitalisation.Results Median age was 83 years and 473 patients (55.6%) were female. Five hundred and two patients (59%) were proteinuria (−) and 349 patients (41%) were proteinuria (+). The composite endpoint and HF rehospitalisation occurred more often in proteinuria (+) individuals than proteinuria (−) individuals (log-rank p=0.006 and p=0.007, respectively); but cardiac death did not (log-rank p=0.139). Multivariable Cox regression analysis showed that the presence of proteinuria was associated with the composite endpoint (HR: 1.47, 95% CI 1.07 to 2.01, p=0.016), and HF rehospitalisation (HR: 1.48, 95% CI 1.07 to 2.05, p=0.020), but not with cardiac death (HR: 1.52, 95% CI 0.83 to 2.76, p=0.172).Conclusions Dipstick proteinuria may be a prognostic marker in patients with HFpEF. Evaluation of proteinuria by a urine dipstick test may be a simple but useful method for risk stratification in HFpEF.UMIN-CTR ID UMIN000021831.

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

Introduction Neither the pathophysiology nor an effective treatment for heart failure with preserved ejection fraction (HFpEF) has been elucidated to date. The purpose of this ongoing study is to elucidate the pathophysiology and prognostic factors for patients with HFpEF admitted to participating institutes. We also aim to obtain insights into the development of new diagnostic and treatment methods by analysing patient background factors, clinical data and follow-up information.Methods and analysis This study is a prospective, multicentre, observational study of patients aged ≥20 years admitted due to acute decompensated heart failure with preserved left ventricular ejection fraction (≥50%) and elevated N-terminal-pro brain natriuretic peptide (NT-proBNP) (≥400 pg/mL). The study began in June 2016, with the participation of Osaka University Hospital and 31 affiliated facilities. We will collect data on history in detail, accompanying diseases, quality of life, frailty score, medication history, and laboratory and echocardiographic data. We will follow-up each patient for 5 years, and collect outcome data on mortality, cause of death, and the number and cause of hospitalisation. The target number of registered cases is 1500 cases in 5 years.Ethics and dissemination The protocol was approved by the Institutional Review Board (IRB) of Osaka University Hospital on 24 February 2016 (ID: 15471), and by the IRBs of the all participating facilities. The findings will be disseminated through peer-reviewed publications and conference presentations.

A 69-year-old woman with palpitations was referred to our hospital for a second session of atrial fibrillation (AF) catheter ablation. She had a history of AF ablation including pulmonary vein (PV) isolation and persistent left superior vena cava (PLSVC) isolation. Electrophysiologic studies showed the veno-atrial connections that had recovered. After PV isolation was performed, AF was induced by atrial premature contraction (APC) from the PLSVC, and AF storm occurred. During PLSVC isolation, AF was not induced by APC from the PLSVC. PLSVC isolation continued during sinus rhythm. The elimination of the PLSVC potential was difficult to confirm because of the far-field potential of the left ventricle. Then, we performed right ventricular pacing. The remaining PLSVC potential was identified. After that, the PLSVC isolation was successful during right ventricular pacing. Complications were not observed. The patient had no recurrence of AF thereafter. Keywords: Persistent left superior vena cava, Atrial fibrillation, Catheter ablation, Ventricular pacing, Non-pulmonary vein foci

The role of B-type natriuretic peptide (BNP) levels as a predictor of arrhythmia recurrence (AR) after atrial fibrillation (AF) ablation remains unclear. In this study, we investigated the association of BNP levels before and 3 months after ablation with the risk of AR. A total of 234 patients undergoing their first session of AF ablation were included (68% male, mean age of 69 years). The cut-off value for discriminating AR was determined based on the maximum value of the area under the receiver operating characteristic (ROC) curve. The impact of BNP levels on AR was evaluated using Cox regression analysis. ROC curve analysis showed that the area under the curve for BNP at 3 months after the procedure was larger (0.714) compared to BNP levels before ablation (0.593). Elevated levels of BNP 3 months after the procedure (>40.5 pg/mL, n = 96) was associated with a higher risk of AR compared to those without elevated levels (34.4% vs. 10.9%, p < 0.01). Multivariate Cox regression analysis revealed that elevated BNP levels were associated with an increased risk of AR (hazard ratio 2.43; p = 0.014). Elevated BNP levels 3 months after AF ablation were a significant prognostic factor in AR, while baseline BNP levels were not.