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Background: The DAPA-HF and DELIVER trials demonstrated the clinical benefits of dapagliflozin in heart failure (HF) patients across the entire ejection fraction (EF) spectrum. However, further investigation is needed for the real-world application of dapagliflozin in HF patients. This study examines the proportion of real-world HF patients eligible for dapagliflozin and evaluates the cost-effectiveness of adding dapagliflozin to current HF therapy., Methods: Data from the nationwide prospective registry, the Korean Acute Heart Failure (KorAHF) registry, were used to determine dapagliflozin eligibility based on the enrollment criteria of the DAPA-HF/DELIVER trials. A cost-utility analysis was conducted using a Markov model to assess the cost-effectiveness of dapagliflozin by comparing it to the standard of care., Results: Out of 5178 KorAHF patients, 48.7% met the enrollment criteria of the DAPA-HF/DELIVER trials, while 89.5% met the label criteria (US Food and Drug Administration, European Medicines Agency, and Korean Ministry of Food and Drug Safety). Eligibility was highest among HF patients with preserved EF (55.3% vs. HF with mildly reduced EF and HF with reduced EF 46.4%). Dapagliflozin proved to be cost-effective, with an incremental cost-effectiveness ratio (ICER) of 4557 US dollar (US$) per quality-adjusted life year, which falls below the US$18,182 willingness-to-pay threshold. The cost-effectiveness benefit was more pronounced in patients with a left ventricular EF (LVEF) ≤ 40% (ICER US$3279 for LVEF ≤ 40% vs. US$8383 for LVEF > 40%)., Conclusions: Discrepancies in dapagliflozin eligibility were observed between real-world data and clinical trial results. The addition of dapagliflozin to HF therapy proved to be highly cost-effective across the entire EF spectrum., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry., Methods: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY)., Results: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY)., Conclusion: There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications., Trial Registration: ClinicalTrials.gov Identifier: NCT01389843., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Aims: Although the hypothesis that metformin is beneficial for patients with diabetes and heart failure (HF) has been steadily raised, there is limited data on metformin use in patients with acute HF. We analyzed the association of metformin on all-cause mortality in hospitalized patients with type 2 diabetes and acute HF., Methods: The Korean Acute Heart Failure registry prospectively enrolled patients hospitalized for acute HF from 2011 to 2014. Among this cohort, we analyzed patients with diabetes with baseline estimated glomerular filtration rate (eGFR) of 30 ml/min/1.73 m 2 or more. We analyzed the all-cause mortality and re-hospitalization for HF within 1 year after discharge. Inverse probability treatment weighting method was used to adjust baseline differences on metformin treatment., Results: The study analyzed data from 1,309 patients with HF and diabetes (mean age 69 years, 56 % male). Among them, 613 (47 %) patients were on metformin at admission. During the median follow-up period of 11 months, 132 (19 %) and 74 (12 %) patients not receiving and receiving metformin treatment died, respectively. The mortality rate was lower in metformin users than in non-users (hazard ratio 0.616 [0.464-0.819] P<0.001). After adjustment, metformin was significantly associated with a lower risk for the mortality (hazard ratio 0.677 [0.495-0.928] P=0.015). In subgroup analyses, this association remains significant irrespective of baseline kidney function (eGFR <60 or ≥60 ml/min/1.73 m 2 , P-for-interaction=0.176) or left ventricular ejection fraction (<40 %, 40-49 %, or ≥50 %, P-for-interaction=0.224)., Conclusions: Metformin treatment at the time of admission was associated with a lower risk for 1-year mortality in patients with diabetes, hospitalized for acute HF., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Masson SAS.)

Background: High glycemic variability (GV) is a poor prognostic marker in cardiovascular diseases. We aimed to investigate the association of GV with all-cause mortality in patients with acute heart failure (HF)., Methods: The Korean Acute Heart Failure registry enrolled patients hospitalized for acute HF from 2011 to 2014. Blood glucose levels were measured at the time of admission, during hospitalization, and at discharge. We included those who had 3 or more blood glucose measurements in this study. Patients were divided into two groups based on the coefficient of variation (CoV) as an indicator of GV. Among survivors of the index hospitalization, we investigated all-cause mortality at 1 year after discharge., Results: The study analyzed 2,617 patients (median age, 72 years; median left-ventricular ejection fraction, 36%; 53% male). During the median follow-up period of 11 months, 583 patients died. Kaplan-Meier curve analysis revealed that high GV (CoV > 21%) was associated with lower cumulative survival (log-rank P < 0.001). Multivariate Cox proportional analysis showed that high GV was associated with an increased risk of 1-year (HR 1.56, 95% CI 1.26-1.92) mortality. High GV significantly increased the risk of 1-year mortality in non-diabetic patients (HR 1.93, 95% CI 1.47-2.54) but not in diabetic patients (HR 1.19, 95% CI 0.86-1.65, P for interaction = 0.021)., Conclusions: High in-hospital GV before discharge was associated with all-cause mortality within 1 year, especially in non-diabetic patients with acute HF., (© 2022. The Author(s).)

Aims: It remains unclear if patients with acute heart failure syndrome (AHFS) need to reach the maximally tolerated doses of renin-angiotensin system blockers (RASBs) or beta-blockers (BBs) to obtain a survival benefit. This study evaluated the dose-response relationship between RASBs or BBs and survival in AHFS patients., Methods and Results: In total, 5331 patients in the Korean Acute Heart Failure registry were analysed based on the doses of RASBs and BBs at discharge. In AHFS patients, RASB use at discharge was associated with a significant reduction in all-cause mortality risk. This effect was dose-dependent for heart failure with reduced ejection fraction (HFrEF) but did not attain statistical significance for heart failure with preserved ejection fraction (HFpEF). BB use at discharge was associated with reduced all-cause mortality in HFrEF patients but not in HFpEF patients. In an additional analysis of 4613 patients with dosage information at the first post-discharge follow-up visit, a significantly higher mortality risk was associated with the maintenance or withdrawal of RASBs compared with up-titrating the dose in HFrEF patients., Conclusion: Using RASBs or BBs at discharge was associated with improved survival. A dose-response relationship between RASBs and all-cause mortality was evident in AHFS patients with a reduced ejection fraction but not BBs. It is important to initiate and up-titrate RASBs to the maximally tolerated dose in AHFS patients during the transition period, especially for patients with a reduced ejection fraction., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims In 2021, vericiguat was approved by the US Food and Drug Administration (FDA) and the European Commission (EC) for reducing cardiovascular mortality and heart failure (HF) hospitalizations in patients with HF with reduced ejection fraction (HFrEF) based on the Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial. However, there has been no report for characterizing the generalizability of vericiguat to real-world clinical practice. Methods and results The Korean Acute Heart Failure (KorAHF) registry is a multicentre prospective cohort study. A total of 5625 patients who were admitted for HF decompensation were consecutively enrolled. We excluded the patients without left ventricular ejection fraction (LVEF) quantification, patients with LVEF > 45%, patients with in-hospital death or urgent heart transplantation, and patients without natriuretic peptide measurement. Among a total of 3014 enrolled patients, there were 21.9% patients with lower systolic blood pressure (SBP) (<100 mmHg) and 20.1% patients without elevated natriuretic peptide. Regarding chronic kidney disease (CKD) status, 5.1% patients had CKD Stage V [estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m 2 ] and 11.8% patients had CKD Stage IV (15 ≤ eGFR < 30 mL/min/1.73 m 2 ). When we analysed these criteria sequentially, 21.9% were excluded from lower SBP, 15.9% were excluded from elevated natriuretic peptide, and 4.2% were excluded from advanced CKD Stage V (9.6% for CKD Stages IV and V). Among the KorAHF registry patients, we found two main reasons for not meeting the inclusion criteria of the VICTORIA trial such as low SBP and non-elevated natriuretic peptide. Conclusions Among the Korean hospitalized HFrEF patients, 94.9% met the FDA/EC label criteria, while 58% met the inclusion criteria of the VICTORIA trial. Our findings suggest the need for better strategies to integrate up-to-date HF treatment in a real-world HF population, especially decompensated HF patients with low SBP and non-elevated natriuretic peptide., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Restoring and maintaining sinus rhythm (SR) in patients with atrial fibrillation (AF) failed to show superior outcomes over rate control strategies in prior randomized trials. However, there is sparse data on their outcomes in patients with acute heart failure (AHF)., Methods: From December 2010 to February 2014, 5,625 patients with AHF from 10 tertiary hospitals were enrolled in the Korean Acute Heart Failure registry, including 1,961 patients whose initial electrocardiogram showed AF. Clinical outcomes of patients who restored SR by pharmacological or electrical cardioversion (SR conversion group, n = 212) were compared to those of patients who showed a persistent AF rhythm (AF persistent group, n = 1,662)., Results: All-cause mortality both in-hospital and during the follow-up (median 2.5 years) were significantly lower in the SR conversion group than in the AF persistent group after adjustment for risk factors (adjusted hazard ratio [HR]; 95% confidence interval [CI] = 0.26 [0.08-0.88], p = 0.031 and 0.59 [0.43-0.82], p = 0.002, for mortality in-hospital and during follow-up, respectively). After 1:3 propensity score matching (SR conversion group = 167, AF persistent group = 501), successful restoration of SR was associated with lower all-cause mortality (HR [95% CI] = 0.68 [0.49-0.93], p = 0.015), heart failure rehospitalization (HR [95% CI] = 0.66 [0.45-0.97], p = 0.032), and composite of death and heart failure rehospitalization (HR [95% CI] = 0.66 [0.51-0.86], p = 0.002)., Conclusions: Patients with AHF and AF had significantly lower mortality in-hospital and during follow-up if rhythm treatment for AF was successful, underscoring the importance of restoring SR in patients with AHF.

Background: To investigate the effect of beta-blockers according to NP levels and HF phenotypes because natriuretic peptide (NP) level can be used to risk-stratify HF patients regardless of left ventricular ejection fraction (LVEF)., Methods: Of 5,625 patients in the Korean acute heart failure registry, we included patients with LVEF and NP levels. HF phenotypes were defined as HF with reduced ejection fraction (HFrEF) (EF ≤ 40%), HF with midrange ejection fraction (HFmrEF) (40% < EF < 50%), and HF with preserved EF (HFpEF) (EF ≥ 50%). Patients were further stratified by NP tertiles. Primary outcome was 5-year all-cause mortality according to beta-blocker use at discharge., Results: Both B-type NP (BNP) (r = -0.279, P < 0.001) and N-terminal pro-BNP (r = -0.186, P < 0.001) levels correlated inversely with LVEF. During a median follow-up duration of 961 days, 1560 (35.3%) patients died. In HFrEF, patients taking beta-blockers showed better survival regardless of NP levels. Regarding HFmrEF, there was no mortality difference between those taking and not taking beta-blockers. In HFpEF, beta-blocker use demonstrated lower mortality in those in the 3rd NP tertile (log-rank P = 0.041) but not in those in the 1st and 2nd NP tertiles (log-rank P > 0.05). After adjusting covariates, the use of beta-blockers was associated with a 38%-reduced mortality (hazard ratio: 0.62; 95% confidence interval: 0.39-0.98; P = 0.040) in HFpEF patients in the 3rd NP tertile but not in those in 1st and 2nd tertiles., Conclusions: We confirm that the use of beta-blockers is beneficial in patients with HFrEF. Furthermore, we extend the benefits of beta-blockers to patients with HFpEF and high NP levels., Clinical Trial Registration: ClinicalTrial.gov identifier: NCT01389843 URL: https://clinicaltrials.gov/ct2/show/NCT01389843., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: Tachycardia is a reversible event that may cause hemodynamic decompensation but may not necessarily cause direct damages to the myocardium. To evaluate the clinical outcomes of patients with heart failure (HF) and atrial fibrillation (AF), whose acute decompensation was tachycardia mediated., Methods and Results: The Korean Acute Heart Failure registry was a prospective registry that consecutively enrolled 5625 patients with acute HF. Patients were classified into three groups according to the rhythm and aggravating factor: (i) 3664 (65.1%) patients with sinus rhythm (SR), (ii) 1033 (18.4%) patients with AF whose decompensation was tachycardia-mediated, AF-TM (+), and (iii) N = 928 (16.5%) patients with AF whose decompensation was not tachycardia-mediated, AF-TM (-). The primary outcomes were in-hospital and post-discharge 1 year all-cause mortality. At admission, the mean heart rate was 90.8 ± 23.4, 86.8 ± 26.8, and 106.3 ± 29.7 beats per minute for the SR, AF-TM (-), and AF-TM (+) groups, respectively. The AF-TM (+) group had more favourable characteristics such as de novo onset HF, less diabetes, ischaemic heart disease, and higher blood pressure than the AF-TM (-) group. In-hospital mortality rates were 5.1%, 6.5%, and 1.7% for SR, AF-TM (-), and AF-TM (+) groups, respectively. In logistic regression analysis, the AF-TM (+) group had lower in-hospital mortality after adjusting the significant covariates (odds ratio, 0.49; 95% confidence interval, 0.26-0.93). The mortality rate did not differ between SR and AF-TM (-) groups. During 1 year follow-up, 990 (18.5%) patients died. In univariate and multivariate Cox proportional regression analyses, there was no difference in 1-year all-cause mortality between the three groups., Conclusions: In patients with HF and AF, patients whose acute decompensation is tachycardia-mediated have better in-hospital, but similar post-discharge outcomes compared with those with SR or those with AF whose decompensation is not tachycardia-mediated., Clinical Trial Registration: ClinicalTrial.gov NCT01389843., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: Machine learning (ML) algorithm can improve risk prediction because ML can select features and segment continuous variables effectively unbiased. We generated a risk score model for mortality with ML algorithms in East-Asian patients with heart failure (HF)., Methods: From the Korean Acute Heart Failure (KorAHF) registry, we used the data of 3683 patients with 27 continuous and 44 categorical variables. Grouped Lasso algorithm was used for the feature selection, and a novel continuous variable segmentation algorithm which is based on change-point analysis was developed for effectively segmenting the ranges of the continuous variables. Then, a risk score was assigned to each feature reflecting nonlinear relationship between features and survival times, and an integer score of maximum 100 was calculated for each patient., Results: During 3-year follow-up time, 32.8% patients died. Using grouped Lasso, we identified 15 highly significant independent clinical features. The calculated risk score of each patient ranged between 1 and 71 points with a median of 36 (interquartile range: 27-45). The 3-year survival differed according to the quintiles of the risk score, being 80% and 17% in the 1st and 5th quintile, respectively. In addition, ML risk score had higher AUCs than MAGGIC-HF score to predict 1-year mortality (0.751 vs. 0.711, P < 0.001)., Conclusions: In East-Asian patients with HF, a novel risk score model based on ML and the new continuous variable segmentation algorithm performs better for mortality prediction than conventional prediction models., Clinical Trial Registration: Unique identifier: INCT01389843 https://clinicaltrials.gov/ct2/show/NCT01389843 ., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Objectives: Evidence for effectiveness of early change from angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) to sacubitril/valsartan is lacking. We aimed to investigate whether early changes to sacubitril/valsartan could improve outcomes in patients with nonischemic dilated cardiomyopathy (DCM) in real-world practice. Materials and Methods : A total of 296 patients with nonischemic DCM who were treated with ARB or ACEI continuously (group A, n = 150) or had their medication switched to sacubitril/valsartan (group S, n = 146) were included. The sacubitril/valsartan group was divided into early change (within 60 days, group S/E, n = 59) and late change (group S/L, n = 87) groups. Changes in echocardiographic parameters from the time of initial diagnosis to the last follow-up were analyzed. Results : Patients in group S showed greater left ventricular (LV) end-diastolic dimension (EDD) (group A vs. S, 61.7 ± 7.4 vs. 66.5 ± 8.0, p < 0.001) and lower LV ejection fraction (LVEF) (28.9 ± 8.2% vs. 23.9 ± 7.5%, p < 0.001) than those in group A at initial diagnosis. During a median follow-up of 76 months, patients in group S/E, ∆ LVEF (%) and ∆ LVESD (mm) were significantly improved compared with those in patients in group A (group A vs. S/E, ∆ LVEF, p = 0.036; ∆ LVESD, p = 0.023) or S/L (group S/E vs. S/L, ∆ LVEF, p = 0.05; ∆ LVESD, p = 0.005). Among patients whose medications were switched to sacubitril/valsartan, those with an earlier change showed a significant correlation with greater LVEF improvement (r = -0.367, p < 0.001) and LV reverse remodeling (r = 0.277, p < 0.001). Conclusions : in patients with nonischemic DCM, an early switch to sacubitril/valsartan was associated with greater improvement in LV function. Patients might benefit in terms of LV function by early switching to sacubitril/valsartan.

Although heart failure with reduced ejection fraction (HFrEF) is a common clinical syndrome and can be modified by the administration of appropriate medical therapy, there is no adequate tool available to perform reliable, economical, early-stage screening. To meet this need, we developed an interpretable artificial intelligence (AI) algorithm for HFrEF screening using electrocardiography (ECG) and validated its performance. This retrospective cohort study included two hospitals. An AI algorithm based on a convolutional neural network was developed using 39,371 ECG results from 17,127 patients. The internal validation included 3,470 ECGs from 2,908 patients. Furthermore, we conducted external validation using 4,362 ECGs from 4,176 patients from another hospital to verify the applicability of the algorithm across different centers. The end-point was to detect HFrEF, defined as an ejection fraction <40%. We also visualized the regions in 12 lead ECG that affected HFrEF detection in the AI algorithm and compared this to the previously documented literature. During the internal and external validation, the areas under the curves of the AI algorithm using a 12 lead ECG for detecting HFrEF were 0.913 (95% confidence interval, 0.902-0.925) and 0.961 (0.951-0.971), respectively, and the areas under the curves of the AI algorithm using a single-lead ECG were 0.874 (0.859-0.890) and 0.929 (0.911-0.946), respectively. The deep learning-based AI algorithm performed HFrEF detection well using not only a 12 lead but also a single-lead ECG. These results suggest that HFrEF can be screened not only using a 12 lead ECG, as is typical of a conventional ECG machine, but also with a single-lead ECG performed by a wearable device employing the AI algorithm, thereby preventing irreversible disease progression and mortality., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2020.)

Background: There are sparse data on the utilization rate of implantable cardioverter-defibrillator (ICD) and its beneficial effects in Korean patients with heart failure with reduced left ventricular ejection fraction (LVEF)., Methods: Among 5,625 acute heart failure (AHF) patients from 10 tertiary university hospitals across Korea, 485 patients with reassessed LVEF ≤ 35% at least 3 months after the index admission were enrolled in this study. The ICD implantation during the follow-up was evaluated. Mortality was compared between patients with ICDs and age-, sex-, and follow-up duration matched control patients., Results: Among 485 patients potentially indicated for an ICD for primary prevention, only 56 patients (11.5%) underwent ICD implantation during the follow-up. Patients with ICD showed a significantly lower all-cause mortality compared with their matched control population: adjusted hazard ratio (HR) (95% confidence interval [CI]) = 0.39 (0.16-0.92), P = 0.032. The mortality rate was still lower in the ICD group after excluding patients with cardiac resynchronization therapy (adjusted HR [95% CI] = 0.09 [0.01-0.63], P = 0.015). According to the subgroup analysis for ischemic heart failure, there was a significantly lower all-cause mortality in the ICD group than in the no-ICD group (HR [95% CI] = 0.20 [0.06-0.72], P = 0.013), with a borderline statistical significance (interaction P = 0.069)., Conclusion: Follow-up data of this large, multicenter registry suggests a significant under-utilization of ICD in Korean heart failure patients with reduced LVEF. Survival analysis implies that previously proven survival benefit of ICD in clinical trials could be extrapolated to Korean patients., Trial Registration: ClinicalTrials.gov Identifier: NCT01389843., Competing Interests: The authors have no potential conflicts of interest to disclosure, (© 2020 The Korean Academy of Medical Sciences.)

Background/aims: This study investigated the prognostic power of corrected QT (QTc) interval in patients with acute heart failure (AHF) according to sex., Methods: We analyzed multicenter Korean Acute Heart Failure registry with patients with AHF admitted from 2011 to 2014. Among them, we analyzed 4,990 patients who were followed up to 5 years. Regarding QTc interval based on 12 lead electrocardiogram, patients were classified into quartiles according to sex., Results: During follow-up with median 43.7 months, 2,243 (44.9%) patients died. The relationship between corrected QT interval and all-cause mortality followed a J-curve relationship. In Kaplan-Meier analysis, both sex had lowest mortality in the second QTc quartile. There were significant prognostic differences between the second and the fourth quartiles in male (log-rank p = 0.002), but not in female (log-rank p = 0.338). After adjusting covariates, the third (hazard ratio [HR], 1.185; 95% confidence interval [CI], 1.001 to 1.404; p = 0.049) and the fourth (HR, 1.404; 95% CI, 1.091 to 1.535; p = 0.003) quartiles demonstrated increased risk of mortality compared to the second quartile in male. In female, however, there was no significant difference across quartiles. QTc interval was associated with 5-year all-cause mortality in J-shape with nadir of 440 to 450 ms in male and 470 to 480 ms in female., Conclusion: QTc interval was an independent predictor of overall death in male, but its significance decreased in female. The relationship between QTc interval and all-cause mortality was J-shaped in both sex.

Background: Although more than one-third of the patients with acute heart failure (AHF) have diabetes mellitus (DM), it is unclear if DM has an adverse impact on clinical outcomes. This study compared the outcomes in patients hospitalized for AHF stratified by DM and left ventricular ejection fraction (LVEF)., Methods: The Korean Acute Heart Failure registry prospectively enrolled and followed 5625 patients from March 2011 to February 2019. The primary endpoints were in-hospital and overall all-cause mortality. We evaluated the impact of DM on these endpoints according to HF subtypes and glycemic control., Results: During a median follow-up of 3.5 years, there were 235 (4.4%) in-hospital mortalities and 2500 (46.3%) overall mortalities. DM was significantly associated with increased overall mortality after adjusting for potential confounders (adjusted hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.03-1.22). In the subgroup analysis, DM was associated with higher a risk of overall mortality in heart failure with reduced ejection fraction (HFrEF) only (adjusted HR 1.14, 95% CI 1.02-1.27). Inadequate glycemic control (HbA1c ≥ 7.0% within 1 year after discharge) was significantly associated with a higher risk of overall mortality compared with adequate glycemic control (HbA1c < 7.0%) (44.0% vs. 36.8%, log-rank p = 0.016)., Conclusions: DM is associated with a higher risk of overall mortality in AHF, especially HFrEF. Well-controlled diabetes (HbA1c < 7.0%) is associated with a lower risk of overall mortality compared to uncontrolled diabetes. Trial registration ClinicalTrial.gov, NCT01389843. Registered July 6, 2011. https://clinicaltrials.gov/ct2/show/NCT01389843.

Objectives and Design: Guideline-directed medical therapy (GDMT) with renin-angiotensin system (RAS) inhibitors and beta-blockers has improved survival in patients with heart failure with reduced ejection fraction (HFrEF). As clinical trials usually do not include very old patients, it is unknown whether the results from clinical trials are applicable to elderly patients with HF. This study was performed to investigate the clinical characteristics and treatment strategies for elderly patients with HFrEF in a large prospective cohort., Setting: The Korean Acute Heart Failure (KorAHF) registry consecutively enrolled 5625 patients hospitalised for acute HF from 10 tertiary university hospitals in Korea., Participants: In this study, 2045 patients with HFrEF who were aged 65 years or older were included from the KorAHF registry., Primary Outcome Measurement: All-cause mortality data were obtained from medical records, national insurance data or national death records., Results: Both beta-blockers and RAS inhibitors were used in 892 (43.8%) patients (GDMT group), beta-blockers only in 228 (11.1%) patients, RAS inhibitors only in 642 (31.5%) patients and neither beta-blockers nor RAS inhibitors in 283 (13.6%) patients (no GDMT group). With increasing age, the GDMT rate decreased, which was mainly attributed to the decreased prescription of beta-blockers. In multivariate analysis, GDMT was associated with a 53% reduced risk of all-cause mortality (HR 0.47, 95% CI 0.39 to 0.57) compared with no GDMT. Use of beta-blockers only (HR 0.57, 95% CI 0.45 to 0.73) and RAS inhibitors only (HR 0.58, 95% CI 0.48 to 0.71) was also associated with reduced risk. In a subgroup of very elderly patients (aged ≥80 years), the GDMT group had the lowest mortality., Conclusions: GDMT was associated with reduced 3-year all-cause mortality in elderly and very elderly HFrEF patients., Trial Registration Number: NCT01389843., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Some patients with heart failure with preserved ejection fraction (HFpEF) experience declining of left-ventricular ejection fraction (LVEF) during follow-up. We aim to investigate the characteristics and outcomes of patients with HF with declining ejection fraction (HFdEF)., Methods: We analyzed a prospective, nationwide multicenter cohort with consecutive patients with acute HF enrolled from March 2011 to December 2014. HFpEF was defined as LVEF ≥ 50% at index admission. After 1 year, HFpEF patients were further classified as HFdEF (LVEF ≥ 50% at admission and < 50% at 1 year), and persistent HFpEF (LVEF ≥ 50% both at admission and 1 year). Primary outcome was 4-year all-cause mortality according to HF type from HFdEF diagnosis., Results: Of patients with HFpEF, 426 (90.4%) were diagnosed as having persistent HFpEF and 45 (9.6%) as having HFdEF. Natriuretic peptide level was an independent predictor of HFdEF (natriuretic peptide level > median: odds ratio: 3.20, 95% confidence interval [CI]: 1.42-7.25, P = 0.005). During 4-year follow-up, patients with HFdEF had higher mortality than those with persistent HFpEF (Log-rank P < 0.001). After adjustment, HFdEF was associated with an almost twofold increased risk for mortality (hazard ratio 1.82, 95% CI 1.13-2.96, P = 0.015). The use of beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists was not associated with improved prognosis of patients with HFdEF., Conclusions: HFdEF is a distinct HF type with grave outcomes. Further investigations that focus on HFdEF are warranted to better understand and develop treatment strategies for these high-risk patients., Clinical Trial Registration: ClinicalTrial.gov identifier: NCT01389843. URL: https://clinicaltrials.gov/ct2/show/NCT01389843.

Objective: Myocardial ischaemia is a leading cause of acute heart failure (AHF). However, optimal revascularisation strategies in AHF are unclear. We aimed to compare two revascularisation strategies, coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI), in patients with AHF., Methods: Among 5625 consecutive patients enrolled prospectively in the Korean Acute Heart Failure registry from March 2011 to February 2014, 717 patients who received CABG or PCI during the index hospitalisation for AHF were included in this analysis. We compared adverse outcomes (death, rehospitalisation for HF aggravation or cardiovascular causes, ischaemic stroke and a composite outcome of death and rehospitalisation for HF aggravation or cardiovascular causes) with the use of propensity score matching., Results: For the propensity score-matched cohort with 190 patients, CABG had a lower risk of all-cause mortality than PCI (83 vs 147 deaths per 1000 patient-years; HR 0.57, 95% CI 0.34 to 0.96, p=0.033) during the median follow-up of 4 years. There was also a trend towards lower rates of rehospitalisation due to cardiovascular events or HF aggravation. Subgroup analysis revealed that the adverse outcomes were significantly lower in the CABG group than in PCI group, especially in patients with old age, three-vessel diseases, significant proximal left anterior descending artery disease and those without left main vessel disease or chronic total occlusion., Conclusions: Compared with PCI, CABG is associated with significant lower all-cause mortality in patients with AHF. Further studies should evaluate proper revascularisation strategies in AHF., Clinical Trial Registration: NCT01389843; Results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: It is unknown whether different β-blockers (BBs) have variable effects on long-term survival of patients with heart failure with reduced ejection fraction (HFrEF). This study compares the effects of two BBs, carvedilol and bisoprolol, on survival in patients with HFrEF., Methods: The Korean Acute Heart Failure (KorAHF) registry is a prospective multicenter cohort that includes 5,625 patients who were hospitalized for acute heart failure (AHF). We selected 3,016 patients with HFrEF and divided this study population into two groups: BB at discharge (n = 1,707) or no BB at discharge (n = 1,309). Among patients with BB at discharge, subgroups were formed based on carvedilol prescription (n = 831), or bisoprolol prescription (n = 553). Propensity score matching analysis was performed., Results: Among patients who were prescribed a BB at discharge, 60.5% received carvedilol and 32.7% received bisoprolol. There was a significant reduction in allcause mortality in those patients with HFrEF prescribed a BB at discharge compared to those who were not (BB vs. no BB, 26.1% vs. 40.8%; hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.52 to 0.67; p < 0.001). However, there was no significant difference in the rate of all-cause mortality between those receiving different types of BB (carvedilol vs. bisoprolol, 27.5% vs. 23.5%; HR, 1.21; 95% CI, 0.99 to 1.47; p = 0.07). Similar results were observed after propensity score matching analysis (508 pairs, 26.2% vs. 23.8%; HR, 1.10; 95% CI, 0.86 to 1.40; p = 0.47)., Conclusion: In the treatment of AHF with reduced EF after hospitalization, mortality benefits of carvedilol and bisoprolol were comparable.

Aims: This study aimed to develop and validate deep-learning-based artificial intelligence algorithm for predicting mortality of AHF (DAHF)., Methods and Results: 12,654 dataset from 2165 patients with AHF in two hospitals were used as train data for DAHF development, and 4759 dataset from 4759 patients with AHF in 10 hospitals enrolled to the Korean AHF registry were used as performance test data. The endpoints were in-hospital, 12-month, and 36-month mortality. We compared the DAHF performance with the Get with the Guidelines-Heart Failure (GWTG-HF) score, Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score, and other machine-learning models by using the test data. Area under the receiver operating characteristic curve of the DAHF were 0.880 (95% confidence interval, 0.876-0.884) for predicting in-hospital mortality; these results significantly outperformed those of the GWTG-HF (0.728 [0.720-0.737]) and other machine-learning models. For predicting 12- and 36-month endpoints, DAHF (0.782 and 0.813) significantly outperformed MAGGIC score (0.718 and 0.729). During the 36-month follow-up, the high-risk group, defined by the DAHF, had a significantly higher mortality rate than the low-risk group(p<0.001)., Conclusion: DAHF predicted the in-hospital and long-term mortality of patients with AHF more accurately than the existing risk scores and other machine-learning models., Competing Interests: The authors have declared that no competing interests exist.

Aims: Nearly 60% of the world's population lives in Asia but little is known about the characteristics and outcomes of Asian patients with heart failure with reduced ejection fraction (HFrEF) compared to other areas of the world., Methods and Results: We pooled two, large, global trials, with similar design, in 13 174 patients with HFrEF (patient distribution: China 833, India 1390, Japan 209, Korea 223, Philippines 223, Taiwan 199 and Thailand 95, Western Europe 3521, Eastern Europe 4758, North America 613, and Latin America 1110). Asian patients were younger (55.0-63.9 years) than in Western Europe (67.9 years) and North America (66.6 years). Diuretics and devices were used less, and digoxin used more, in Asia. Mineralocorticoid receptor antagonist use was higher in China (66.3%), the Philippines (64.1%) and Latin America (62.8%) compared to Europe and North America (range 32.8% to 49.6%). The rate of cardiovascular death/heart failure hospitalization was higher in Asia (e.g. Taiwan 17.2, China 14.9 per 100 patient-years) than in Western Europe (10.4) and North America (12.8). However, the adjusted risk of cardiovascular death was higher in many Asian countries than in Western Europe (except Japan) and the risk of heart failure hospitalization was lower in India and in the Philippines than in Western Europe, but significantly higher in China, Japan, and Taiwan., Conclusion: Patient characteristics and outcomes vary between Asia and other regions and between Asian countries. These variations may reflect several factors, including geography, climate and environment, diet and lifestyle, health care systems, genetics and socioeconomic influences., (© 2018 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background Many patients with heart failure ( HF ) with reduced ejection fraction ( HF r EF ) experience improvement or recovery of left ventricular ejection fraction ( LVEF ). Data on clinical characteristics, outcomes, and medical therapy in patients with HF with improved ejection fraction (HFiEF) are scarce. Methods and Results Of 5625 consecutive patients hospitalized for acute HF in the KorAHF (Registry [Prospective Cohort] for Heart Failure in Korea) study, 5103 patients had baseline echocardiography and 2302 patients had follow-up echocardiography at 12 months. HF phenotypes were defined as persistent HF r EF ( LVEF ≤40% at baseline and at 1-year follow-up), HF i EF ( LVEF ≤40% at baseline and improved up to 40% at 1-year follow-up), HF with midrange ejection fraction (LVEF between 40% and <50%), and HF with preserved ejection fraction ( LVEF ≥50%). The primary outcome was 4-year all-cause mortality from the time of HF i EF diagnosis. Among 1509 HF r EF patients who had echocardiography 1 year after index hospitalization, 720 (31.3%) were diagnosed as having HF i EF . Younger age, female sex, de novo HF , hypertension, atrial fibrillation, and β-blocker use were positive predictors and diabetes mellitus and ischemic heart disease were negative predictors of HF i EF . During 4-year follow-up, patients with HF i EF showed lower mortality than those with persistent HF r EF in univariate, multivariate, and propensity-score-matched analyses. β-Blockers, but not renin-angiotensin system inhibitors or mineralocorticoid receptor antagonists, were associated with a reduced all-cause mortality risk (hazard ratio: 0.59; 95% CI , 0.40-0.87; P=0.007). Benefits for outcome seemed similar among patients receiving low- or high-dose β-blockers (log-rank, P=0.304). Conclusions HF i EF is a distinct HF phenotype with better clinical outcomes than other phenotypes. The use of β-blockers may be beneficial for these patients. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT01389843.

Background Many hospitalized patients with heart failure and reduced ejection fraction ( HF r EF ) have a slow heart rate at discharge, and the effect of β-blockers may be reduced in those patients. We sought to examine the variable effect of β-blockers on clinical outcomes according to the discharge heart rate of hospitalized HF r EF patients. Methods and Results The KorAHF (Korean Acute Heart Failure) registry consecutively enrolled 5625 patients hospitalized for acute heart failure. In this analysis, we included patients with HF r EF (left ventricular ejection fraction ≤40%). Slow heart rate was defined as <70 beats per minute regardless of the use of β-blockers. The primary outcome was 1-year all-cause postdischarge death according to heart rate. Among 2932 patients with HF r EF , 840 (29%) had a slow heart rate and 56% received β-blockers at discharge. Patients with slow heart rates were older and had lower 1-year mortality than those with high heart rates ( P<0.001). A significant interaction between discharge heart rate and β-blocker use was observed ( P<0.001 for interaction). When stratified, only patients without a β-blocker prescription and with a high heart rate showed higher 1-year mortality. In a Cox-proportional hazards regression analysis, β-blocker prescription at discharge was associated with 24% reduced risk for 1-year mortality in patients with high heart rates (hazard ratio: 0.76; 95% CI, 0.61-0.95) but not in those with slow heart rates (hazard ratio: 1.02; 95% CI, 0.68-1.55). Conclusions Many patients with acute heart failure have slow discharge heart rates, and β-blockers may have a limited effect on HF r EF and slow discharge heart rate. Clinical Trial Registration URL : http://www.clinicaltrial.gov . Unique identifier: NCT 01389843.

Background: Identifying patients with acute heart failure (HF) at high risk for readmission or death after hospital discharge will enable the optimization of treatment and management. The objective of this study was to develop a risk score for 30-day HF-specific readmission or death in Korea., Methods: We analyzed the data from the Korean Acute Heart Failure (KorAHF) registry to develop a risk score. The model was derived from a multiple logistic regression analysis using a stepwise variable selection method. We also proposed a point-based risk score to predict the risk of 30-day HF-specific readmission or death by simply summing the scores assigned to each risk variable. Model performance was assessed using an area under the receiver operating characteristic curve (AUC), the Hosmer-Lemeshow goodness-of-fit test, the net reclassification improvement (NRI), and the integrated discrimination improvement (IDI) index to evaluate discrimination, calibration, and reclassification, respectively., Results: Data from 4566 patients aged ≥40 years were included in the analysis. Among them, 446 (9.8%) had 30-day HF-specific readmission or death. The final model included 12 independent variables (age, New York Heart Association functional class, clinical history of hypertension, HF admission, chronic obstructive pulmonary disease, etiology of cardiomyopathy, systolic blood pressure, left ventricular ejection fraction, serum sodium, brain natriuretic peptide, N-terminal prohormone of brain natriuretic peptide at discharge, and prescription of β-blockers and angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists at discharge). The point risk score showed moderate discrimination (AUC of 0.710; 95% confidence interval, 0.685-0.735) and good calibration (χ 2 =8.540, p=0.3826)., Conclusions: The risk score for the prediction of the risk of 30-day HF-specific readmission or death after hospital discharge was developed using 12 predictors. It can be utilized to guide appropriate interventions or care strategies for patients with HF., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The clinical characteristics and outcomes of acute heart failure (AHF) according to left ventricular ejection fraction (LVEF) have not been fully elucidated, especially for patients with mid-range LVEF. We performed a comprehensive comparison of the epidemiology, patterns of in-hospital management, and clinical outcomes in AHF patients with different LVEF categories., Methods and results: The Korean Acute Heart Failure (KorAHF) registry is a prospective multicenter cohort of hospitalized AHF patients in Korea. A total of 5,374 patients enrolled in the KorAHF registry were classified according to LVEF based on the 2016 ESC guidelines. More than half of the HF patients (58%) had reduced EF (HFrEF), 16% had mid-range EF (HFmrEF), and 25% had preserved EF (HFpEF). The HFmrEF patients showed intermediate epidemiological profiles between HFrEF and HFpEF and had a propensity to present as de-novo HF with ischemic etiology. Patients with lower LVEF had worse short-term outcomes, and the all-cause in-hospital mortality, including urgent heart transplantation, of HFrEF, HFmrEF, and HFpEF was 7.1%, 3.6%, and 3.0%, respectively. Overall, discharged AHF patients showed poor 3-year all-cause death up to 38%, which was comparable between LVEF subgroups (P=0.623)., Conclusions: Each LVEF subgroup of AHF patients was a heterogeneous population with diverse characteristics, which have a significant effect on the clinical outcomes. This finding suggested that focused phenotyping of AHF patients could help identify the optimal management strategy and develop novel effective therapies.

Background: We investigated the role of nutritional risk index (NRI) in predicting 1-year mortality in patients with acute decompensated heart failure (ADHF)., Methods: Among 5,625 cohort patients enrolled in Korean Acute Heart Failure (KorAHF) Registry, a total of 5,265 patients who were possible to calculate NRI [NRI = (1.519 x serum albumin [g/dl]) + (41.7 x weight [kg]/ideal body weight [kg])] were enrolled. The patients were divided into 4 groups according to the NRI quartile; Q1 <89 (n = 1121, 69.9 ± 14.5 years, 632 males), Q2 89-95 (n = 1234, 69.7 ± 14.4 years, 677 males), Q3 95-100 (n = 1199, 68.8 ± 14.0 years, 849 males), Q4 >100 (n = 1711, 65.6 ± 14.5 years, 779 males). Primary end-point was all-cause mortality at 1-year clinical follow-up., Results: The 1-year mortality was significantly increased as the NRI quartile decreased, and the lowest NRI quartile was associated with the highest 1-year mortality (Q1: 27.5% vs. Q2: 20.9% vs. Q3: 12.9% vs. Q4: 8.7%, linear p <0.001). On Kaplan-Meier survival analysis, the significant inter-quartile difference was observed (p <0.001 for all). In multivariate analysis using Cox proportional hazard regression, the lowest NRI quartile was an independent predictor of 1-year mortality in patients with ADHF., Conclusions: Poor nutritional status as assessed by NRI and quartile grading of NRI was associated with 1-year mortality in Korean patients with ADHF. The assessment of nutritional status by NRI may provide additional prognostic information and thus would be useful in the risk stratification of the patients with ADHF., Competing Interests: The authors have declared that no competing interests exist.

Background: In clinical practice, a risk prediction model is an effective solitary program to predict prognosis in particular patient groups. B-type natriuretic peptide (BNP)and N-terminal pro-b-type natriuretic peptide (NT-proBNP) are widely recognized outcome-predicting factors for patients with heart failure (HF).This study derived external validation of a risk score to predict 1-year mortality after discharge in hospitalized patients with HF using the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC)program data. We also assessed the effect of adding BNP or NT-proBNP to this risk score model in a Korean HF registry population., Method and Results: We included 5625 patients from the Korean acute heart failure registry (KorAHF) and excluded those who died in hospital. The MAGGIC constructed a risk score to predict mortality in patients with HF by using 13 routinely available patient characteristics (age, gender, diabetes, chronic obstructive pulmonary disorder (COPD), HF diagnosed within the last 18 months, current smoker, NYHA class, use of beta blocker, ACEI or ARB, body mass index, systolic blood pressure, creatinine, and EF). We added BNP or NT-proBNP, which are the most important biomarkers, to the MAGGIC risk scoring system in patients with HF. The outcome measure was 1-year mortality. In multivariable analysis, BNP or NT-proBNP independently predicted death. The risk score was significantly varied between alive and dead groups (30.61 ± 6.32 vs. 24.80 ± 6.81, p < 0.001). After the conjoint use of BNP or NT-proBNP and MAGGIC risk score in patients with HF, a significant difference in risk score was noted (31.23 ± 6.46 vs. 25.25 ± 6.96, p < 0.001).The discrimination abilities of the risk score model with and without biomarker showed minimal improvement (C index of 0.734 for MAGGIC risk score and 0.736 for MAGGIC risk score plus BNP or NT-proBNP, p = 0.0502) and the calibration was found good. However, we achieved a significant improvement in net reclassification and integrated discrimination for mortality (NRI of 33.4%,p < 0.0001 and IDI of 0.002, p < 0.0001)., Conclusion: In the KorAHF, the MAGGIC project HF risk score performed well in a large nationwide contemporary external validation cohort. Furthermore, the addition of BNP or NT-proBNPto the MAGGIC risk score was beneficial in predicting more death in hospitalized patients with HF., Competing Interests: The authors have declared that no competing interests exist.

Background Although current guidelines now define heart failure with midrange ejection fraction ( HF mr EF ) as HF with a left ventricular EF of 40% to 49%, there are limited data on response to guideline-directed medical therapy in patients with HF mr EF . The current study aimed to evaluate the association between β-blocker, renin-angiotensin system blocker ( RASB ), or aldosterone antagonist ( AA ) treatment with clinical outcome in patients with HF mr EF . Methods and Results We performed a patient-level pooled analysis on 1144 patients with HF mr EF who were hospitalized for acute HF from the Kor HF (Korean Heart Failure) and Kor AHF (Korean Acute Heart Failure) registries. The study population was divided between use of β-blocker, RASB , or AA to evaluate the guideline-directed medical therapy in patients with HF mr EF . Sensitivity analyses, including propensity score matching and inverse-probability-weighted methods, were performed. The use of β-blocker in the discharge group showed significantly lower rates of all-cause mortality compared with those who did not use a β-blocker (β-blocker versus no β-blocker, 30.7% versus 38.2%; hazard ratio, 0.758; 95% confidence interval, 0.615-0.934; P=0.009). Similarly, the RASB use in the discharge group was associated with the lower risk of mortality compared with no use of RASB ( RASB versus no RASB , 31.9% versus 38.1%; hazard ratio, 0.76; 95% confidence interval, 0.618-0.946; P=0.013). However, there was no significant difference in all-cause mortality between AA and no AA in the discharge group ( AA versus no AA , 34.2% versus 34.0%; hazard ratio, 1.063; 95% confidence interval, 0.858-1.317; P=0.578). Multiple sensitivity analyses showed similar trends. Conclusions For treatment of acute HFmrEF after hospitalization, β-blocker and RASB therapies on discharge were associated with reduced risk of all-cause mortality. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01389843.

Objectives: Hyponatraemia is a well-known predictor of clinical outcomes in heart failure (HF). However, the mechanism remains poorly understood. Previous reports suggest that hyponatraemia is related to right HF. We sought to evaluate the association between right ventricular (RV) dysfunction and hyponatraemia, and the impact of this relationship on the prognosis of patients with acute heart failure (AHF)., Methods: This is a nested case-control study of the Korean Acute Heart Failure registry. Among 2935 AHF patients enrolled prospectively and consecutively at four tertiary hospitals in Korea from 2011 to 2014, 116 patients with severe persistent hyponatraemia, defined as serum sodium level <130 mmol/L at admission and <135 mmol/L before discharge, were matched with 232 controls, based on propensity scores for hyponatraemia. RV function was assessed with fractional area change (FAC) by echocardiography., Results: RV dysfunction (FAC <35%) was more prevalent in patients with severe persistent hyponatraemia than in those without (81.0% vs 33.6%, p<0.001). Hyponatraemia was strongly associated with RV dysfunction (adjusted OR 8.00, 95% CI 4.50 to 14.22, p<0.001), but not with left ventricular dysfunction (adjusted OR 1.21, 95% CI 0.74 to 1.50, p=0.308). RV dysfunction was an independent predictor of all-cause mortality, after adjustment for hyponatraemia (adjusted HR 2.20, 95% CI 1.53 to 3.15, p<0.001), while hyponatraemia was not (adjusted HR 1.33, 95% CI 0.94 to 1.87, p=0.108)., Conclusions: In patients with AHF, hyponatraemia was more common with RV dysfunction. RV dysfunction, rather than hyponatraemia, was more significantly related with patients' prognosis. Thus, the utility of RV dysfunction instead of hyponatraemia per se should be considered in HF risk models., Trial Registration Number: Korean Acute Heart Failure registry NCT01389843; Results., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background/aims: Fluid retention occurs in patients with heart failure, accounting for dyspnea. We investigated the diagnostic implication of body fluid status, assessed by bio-impedance analysis (BIA), in acute heart failure (AHF) among patients who presented with dyspnea., Methods: A total of 100 patients who presented with dyspnea and suspected with AHF were analyzed in this study. We enrolled 50 AHF and 50 non-AHF patients discriminated through echocardiographic analysis and Framingham criteria and were matched by age and sex. Body composition was analyzed using a multifrequency BIA., Results: AHF patients demonstrated higher extracellular water (ECW)/total body water (TBW) compared with non-AHF patients (0.412 ± 0.017 vs. 0.388 ± 0.023, p < 0.001). A significant difference of ECW/TBW between AHF patients and nonAHF patients was noted when the upper extremities, trunk, and lower extremities were analyzed (all p < 0.001, respectively). ECW/TBW was not different between patients with reduced ejection fraction (EF) and preserved EF along body compartments. The best cut-off value to predict AHF was > 0.412 at lower extremities with sensitivity and specificity of 0.780 and 0.960. The ECW/TBW of the lower extremities (ECW/TBWL) was correlated with log B-type natriuretic peptide (BNP) levels (r = 0.603, p < 0.001) and also improved the net reclassification improvement and integrated discriminated improvement when added to log BNP level. Multivariate analysis revealed that ECW/TBWL > 0.412 had an independent association with AHF patients (p = 0.011)., Conclusion: The ECW/TBWL was higher in patients with dyspnea caused by AHF than their counterparts and demonstrated an independent diagnostic implication. It may be a promising marker to diagnose AHF at bedside.

Background: Renin-angiotensin system blockade (RAB) is the cornerstone in the management of patients with heart failure. However, the benefit of RAB in patients with accompanying severe renal impairment is not clear. We aimed to examine the effect of RAB and the differential effect of RAB depending on renal replacement (RR) in patients with severe renal insufficiency and acute heart failure., Methods and Results: Among 5625 patients from the Korean Acute Heart Failure registry, 673 in-hospital survivors (70.9 ± 12.8 years, 376 men) who had left ventricular ejection fraction < 40% and estimated glomerular filtration rate < 30 mL/min/1.73 m 2 during hospitalization were analyzed. The inverse probability of treatment weighting (IPTW)-adjusted survival analysis was used to compare the composite of all-cause mortality and rehospitalization between patients with and without pre-discharge RAB. A total of 334 (49.6%) adverse events were observed during the 1-year follow-up. The IPTW-adjusted Kaplan-Meier survival analysis showed that the 1-year event rate was 48.7% and 53.8% for patients with RAB and those without, respectively (log rank p = 0.048). RAB was significantly related to better prognosis in patients receiving RR therapy (hazard ratio [HR] = 0.436 [0.269-0.706], p = 0.001), but not in patients not receiving RR therapy (HR 0.956 [0.731-1.250], p = 0.742) in a weighted cohort (p for interaction = 0.005)., Conclusions: Early RAB treatment in patients with heart failure and severe renal insufficiency was related to better prognosis. The benefit of RAB was particularly prominent in patients receiving RR therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The optimal time for initiating β-blocker (BB) treatment in patients with severe acute decompensated heart failure requiring inotropic therapy has not been well defined. We evaluated the effect of predischarge initiation of BB treatment on clinical outcomes., Methods: Among the 5625 patients enrolled in the Korean Acute Heart Failure (KorAHF) registry, 672 BB-naive patients suffering from heart failure with reduced ejection fraction (median, 67.0 years; 62.5% male; median left ventricular ejection fraction, 24.1%) who received inotropic support during hospitalization were evaluated. We compared the risk of post-discharge mortality and rehospitalization between groups with (n = 282) and without (n = 390) pre-discharge BB treatment., Results: During a median follow-up of 2.6 years, all-cause mortality occurred in 252 patients (37.5%). Those who received pre-discharge BB treatment showed lower 2-year mortality rates compared with those who did not (21.3% vs 39.3%; P < 0.001). In a Cox proportional hazards model, all-cause mortality was consistently lower in pre-discharge BB groups after multivariable adjustment (hazard ratio, 0.69; 95% confidence interval, 0.50-0.95; P = 0.025) and adjustment for propensity score methods using the inverse probability of treatment weighting (hazard ratio, 0.70; 95% confidence interval, 0.52-0.93; P = 0.016). The same trend was observed for secondary outcomes of rehospitalization for any cause and rehospitalization for heart failure. Pre-discharge BB was associated with higher rates of BB prescription after 6 (90.1% vs 23.9%; P < 0.001) and 12 (88.9% vs 25.0%; P < 0.001) months., Conclusions: Pre-discharge BB initiation is associated with better clinical outcomes after severe acute decompensated heart failure episodes requiring inotropic therapy., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: The outcomes of heart failure (HF) with mid-range ejection fraction (HFmrEF) have been rarely studied, and follow-up data on left ventricular ejection fraction (LVEF) are scarse.Methods and Results:Patients were selected from a prospective multicenter registry of patients hospitalized for acute HF and then classified in the improved group if they exhibited %LVEF change ≥5 with follow-up LVEF ≥50%. Follow-up LVEF reported at least 90 days after discharge was used for classification. Of the 3,085 patients with acute HF, 454 were classified in the HFmrEF, and 276 had follow-up data. Of these 276 patients, 34.1% were classified in the improved group. Multivariate analysis revealed that hypertension, higher heart rate, lower serum sodium level, and maintenance therapy with β-blocker were associated with improved LVEF. The survival rate was significantly higher in the improved group than in the other groups. Young age and maintenance therapy with renin-angiotensin system blockers or aldosterone antagonists were significantly associated with better survival in HFmrEF., Conclusions: One-third of HFmrEF patients showed improved LVEF; moreover, the survival rate in the improved group was higher than the other groups. Renin-angiotensin system blockers and aldosterone antagonists could improve the survival of HFmrEF patients.

Background: To describe the baseline characteristics of patients with heart failure and preserved left ventricular ejection fraction enrolled in the PARAGON-HF trial (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in HFpEF) comparing sacubitril/valsartan to valsartan in reducing morbidity and mortality., Methods and Results: We report key demographic, clinical, and laboratory findings, and baseline therapies, of 4822 patients randomized in PARAGON-HF, grouped by factors that influence criteria for study inclusion. We further compared baseline characteristics of patients enrolled in PARAGON-HF with those patients enrolled in other recent trials of heart failure with preserved ejection fraction (HFpEF). Among patients enrolled from various regions (16% Asia-Pacific, 37% Central Europe, 7% Latin America, 12% North America, 28% Western Europe), the mean age of patients enrolled in PARAGON-HF was 72.7±8.4 years, 52% of patients were female, and mean left ventricular ejection fraction was 57.5%, similar to other trials of HFpEF. Most patients were in New York Heart Association class II, and 38% had ≥1 hospitalizations for heart failure within the previous 9 months. Diabetes mellitus (43%) and chronic kidney disease (47%) were more prevalent than in previous trials of HFpEF. Many patients were prescribed angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (85%), β-blockers (80%), calcium channel blockers (36%), and mineralocorticoid receptor antagonists (24%). As specified in the protocol, virtually all patients were on diuretics, had elevated plasma concentrations of N-terminal pro-B-type natriuretic peptide (median, 911 pg/mL; interquartile range, 464-1610), and structural heart disease., Conclusions: PARAGON-HF represents a contemporary group of patients with HFpEF with similar age and sex distribution compared with prior HFpEF trials but higher prevalence of comorbidities. These findings provide insights into the impact of inclusion criteria on, and regional variation in, HFpEF patient characteristics., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01920711., (© 2018 American Heart Association, Inc.)

Background: After introduction of up-titration strategy, there are limited data on comparison between the effects of angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blocker (ARB) in patients with heart failure with reduced ejection fraction (HFrEF). The study sought to investigate the association between treatment with ARB at discharge and clinical outcomes in patients with HFrEF compared with treatment with ACEI or no renin angiotensin system blocker (RASB)., Methods: The KorAHF registry is a prospective multicenter cohort and included patients who were hospitalized for acute heart failure (AHF). We studied 3005 patients with HFrEF (<40%), and divided into ARB (n=1190), ACEI (n=1090), and no RASB (n=725) groups. Propensity score matching was performed., Results: All-cause death occurred in 346 patients (29.1%) in the ARB group, 315 patients (28.9%) in the ACEI group, and 305 (42.1%) in the no RASB group. After propensity score matching (ARB vs. ACEI, 827 pairs), there was no significant difference between the two groups in the rate of death (HR 0.91, 95% CI 0.76-1.09, p=0.32). All-cause death was significantly lower in the ARB group than in the no RASB group (ARB vs. no RASB, 538 pairs, HR 0.69, 95% CI 0.56-0.83, p<0.001). The ARB group had a significantly lower discontinuation rate than the ACEI group (20.8% vs. 33.6%, p<0.001)., Conclusions: For treatment of AHF with reduced EF after hospitalization, ARB at discharge shows a mortality benefit comparable to that of ACEI. In addition, tolerability of medication was greater for ARB than for ACEI., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: This study sought to examine the impact of door-to-diuretic (D2D) time on mortality in patients with acute heart failure (AHF) who were presenting to an emergency department (ED)., Background: Most patients with AHF present with congestion. Early decongestion with diuretic agents could improve their clinical outcomes., Methods: The Korea Acute Heart Failure registry enrolled 5,625 consecutive patients hospitalized for AHF. For this analysis, the study included patients who received intravenous diuretic agents within 24 h after ED arrival. Early and delayed groups were defined as D2D time ≤60 min and D2D time >60 min, respectively. The primary outcomes were in-hospital death and post-discharge death at 1 month and 1 year on the basis of D2D time., Results: A total of 2,761 patients met the inclusion criteria. The median D2D time was 128 min (interquartile range: 63 to 243 min), and 663 (24%) patients belonged to the early group. The baseline characteristics were similar between the groups. The rate of in-hospital death did not differ between the groups (5.0% vs. 5.1%; p > 0.999), nor did the post-discharge 1-month (4.0% vs. 3.0%; log-rank p = 0.246) and 1-year (20.6% vs. 19.3%; log-rank p = 0.458) mortality rates. Get With the Guidelines-Heart Failure risk score was calculated for each patient. In multivariate analyses with adjustment for Get With the Guidelines-Heart Failure risk score and other significant clinical covariates and propensity-matched analyses, D2D time was not associated with clinical outcomes., Conclusions: The D2D time was not associated with clinical outcomes in a large prospective cohort of patients with AHF who were presenting to an ED. (Registry [Prospective Cohort] for Heart Failure in Korea [KorAHF]; NCT01389843)., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Worsening renal function (WRF) is associated with adverse outcomes in patients with heart failure. We investigated the predictors and prognostic value of WRF during admission, in patients with preserved ejection fraction (HFpEF) versus those with reduced ejection fraction (HFrEF)., Methods and Results: A total of 5625 patients were enrolled in the KorAHF (Korean Acute Heart Failure) registry. WRF was defined as an absolute increase in creatinine of ≥0.3 mg/dL. Transient WRF was defined as recovery of creatinine at discharge, whereas persistent WRF was indicated by a nonrecovered creatinine level. HFpEF and HFrEF were defined as a left ventricle ejection fraction ≥50% and ≤40%, respectively. Among the total population, WRF occurred in 3101 patients (55.1%). By heart failure subgroup, WRF occurred more frequently in HFrEF (57.0% versus 51.3%; P <0.001 in HFrEF and HFpEF). Prevalence of WRF increased as creatinine clearance decreased in both heart failure subgroups. Among various predictors of WRF, chronic renal failure was the strongest predictor. WRF was an independent predictor of adverse in-hospital outcomes (HFrEF: odds ratio; 2.75; 95% confidence interval, 1.50-5.02; P =0.001; HFpEF: odds ratio, 9.48; 95% confidence interval, 1.19-75.89; P =0.034) and 1-year mortality (HFrEF: hazard ratio, 1.41; 95% confidence interval, 1.12-1.78; P =0.004 versus HFpEF: hazard ratio, 1.72; 95% confidence interval, 1.23-2.42; P =0.002). Transient WRF was a risk factor for 1-year mortality, whereas persistent WRF had no additive risk compared to transient WRF., Conclusions: In patients with acute heart failure patients, WRF is an independent predictor of adverse in-hospital and follow-up outcomes in both HFrEF and HFpEF, though with a different effect size., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01389843., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objective: There are conflicting results among previous studies regarding the prognosis of heart failure with preserved ejection fraction (HFpEF) compared with heart failure with reduced ejection fraction (HFrEF). This study aimed to compare the outcomes of patients with de novo acute heart failure (AHF) or acute decompensated HF (ADHF) according to HFpEF (EF≥50%), or HFrEF (EF<40%) and to define the prognosis of patients with HF with mid-range EF (HFmrEF, 40≤EF<50%)., Methods: Between March 2011 and February 2014, 5625 consecutive patients with AHF were recruited from 10 university hospitals. A total of 5414 (96.2%) patients with EF data were enrolled, which consisted of 2867 (53.0%) patients with de novo and 2547 (47.0%) with ADHF. Each of the enrolled group was stratified by EF., Results: In de novo, all-cause death rates were not significantly different between HFpEF and HFrEF (HFpEF vs HFrEF, 206/744 (27.7%) vs 438/1631 (26.9%), HR adj 1.15, 95% CI 0.96 to 1.38, p=0.14). However, among patients with ADHF, HFrEF had a significantly higher mortality rate compared with HFpEF (HFpEF vs HFrEF, 245/613 (40.0%) vs 694/1551 (44.7%), HR adj 1.25, 95% CI 1.06 to 1.47, p=0.007). Also, in ADHF, HFmrEF was associated with a significantly lower mortality rate within 1 year compared with HFrEF (HFmrEF vs HFrEF, 88/383 (23.0%) vs 430/1551 (27.7%), HR adj 1.31, 95% CI 1.03 to 1.65, p=0.03), but a significantly higher mortality rate after 1 year compared with HFpEF (HFmrEF vs HFpEF, 83/295 (28.1%) vs 101/469 (21.5%), HR adj 0.70, 95% CI 0.52 to 0.96, p=0.02)., Conclusions: HFpEF may indicate a better prognosis compared with HFrEF in ADHF, but not in de novo AHF. For patients with ADHF, the prognosis associated with HFmrEF was similar to that of HFpEF within the first year following hospitalisation and similar to HFrEF 1  year after hospitalisation., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Hyponatremia is a well-known risk factor for worse outcomes in heart failure (HF) patients. The impact of hyponatremia according to the ejection fraction (EF) is unclear. We evaluated the prognostic value of hyponatremia according to HF type., Methods and Results: The Korea Acute Heart Failure (KorAHF) registry consecutively enrolled 5625 patients. Hyponatremia was defined as serum sodium level<135mmol/L at hospital admission. HF with preserved and reduced ejection fraction were defined as an LVEF ≥50% and LVEF ≤40%, respectively. Among 5103 patients with available EF, 2088 (60%) had HFrEF, and 1284 (25%) had HFpEF. There was no difference in serum sodium level between the groups (HFrEF: 137.4±4.7mmol/L vs. HFpEF: 137.5±5.0mmol/L, P=0.710). Hyponatremic patients had higher in-hospital mortality or urgent heart transplantation in all (11.3% vs. 4.5%, P<0.001), in HFrEF (13.1% vs. 4.9%, P<0.001), and in HFpEF (6.0% vs. 1.9%, P<0.001). After adjustment for significant covariates, hyponatremia was associated with 1.5 fold increased risk for 1-year post-discharge death in the HFrEF group (HR, 1.52; 95% CI, 1.24-1.86), but not in the HFpEF group (HR, 1.16; 95% CI, 0.84-1.61). During admission, the sodium status changed in 22% of the patients and the discharge sodium status had greater prognostic value., Conclusions: Hyponatremia is independent of HF type. Hyponatremia is a significant risk factor for adverse in-hospital outcomes; however its long-term prognostic value is only limited to patients with HFrEF, but not for those with HFpEF., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This study aimed to assess the relationship between on-treatment blood pressure (BP) and clinical outcomes of patients with heart failure (HF)., Background: Lower BP has been reported to be related to increased mortality in various cardiovascular diseases. The optimal BP level for patients already experiencing HF is contentious., Methods: The Korean Acute Heart Failure registry prospectively enrolled a total of 5,625 consecutive patients hospitalized for acute HF in 10 tertiary university hospitals in Korea between March 2011 and February 2014. Clinical profiles including BP were collected at admission, discharge, and during outpatient follow-up. Mean on-treatment BP was calculated from BP at discharge and at each follow-up visit. We evaluated the effects of mean on-treatment BP on the clinical outcomes of patients., Results: Patients were followed up for a median 2.2 years. One-year mortality after discharge was 18.2%. The relationship between on-treatment BP and all-cause mortality followed a reversed J-curve relationship. A nonlinear, multivariable Cox proportional hazard model identified a nadir of systolic and diastolic BPs of 132.4/74.2 mm Hg in patients, for whom the mortality rate was lowest (p < 0.0001). The relationship with increased mortality above and below the reference BP was more definitive for diastolic BP and for HF with a preserved ejection fraction., Conclusions: Systolic and diastolic BPs <130/70 mm Hg at discharge and during follow-up was associated with worse survival in HF patients. These data suggest that the lowest BP possible might not be an optimal target for HF patients. Further studies should establish a proper BP goal in HF patients. (Registry [Prospective Cohort] for Heart Failure in Korea [KorAHF]; NCT01389843)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Very little data is available to evaluate the gender-specific role of N-terminal pro-B type natriuretic peptide (NT-proBNP). This study was performed to investigate whether there is a gender difference in the prognostic value of NT-proBNP in patients hospitalized for heart failure (HF).Methods and Results:A total of 2,280 patients hospitalized with HF (67.9±14.3 years, 50.9% women) from the nationwide registry database were analyzed. Composite events including all-cause mortality and HF readmission were assessed. During the mean follow-up period of 1,245±824 days, there were 1,067 cases of composite events (49.7%). NT-proBNP levels were significantly higher in patients with events than those without in both genders (P<0.001 for each). A higher NT-proBNP level was an independent predictor of events (highest vs. lowest tertile: hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.25-2.43; P=0.001) in men, even after controlling for potential confounders. However, NT-proBNP was not associated with the occurrence of composite events in women in the same multivariable analysis (P>0.05)., Conclusions: In patients with HF, the NT-proBNP level seems to be a more valuable marker in the prediction of long-term mortality and HF readmission in men than in women.

Background: Hemoconcentration (HC) is associated with reduced mortality, whereas hyponatremia (HN) has been associated with an increased risk of adverse outcomes in patients with acute decompensated heart failure (ADHF). We sought to determine if the presence of HN influences the beneficial prognostic value of HC in ADHF patients., Methods: We analyzed 2046 ADHF patients from the Korean Heart Failure Registry. We defined HC as an increased hemoglobin level from admission to discharge, and HN as sodium <135mmol/L at admission. Our primary composite endpoint was all-cause mortality and/or HF re-hospitalization., Results: Overall, HC occurred in 889 (43.5%) patients and HN was observed in 418 patients (20.4%). HC offered higher 2-year event-free survival in patients without HN (73.2% vs. 63.1% for no-HC, log-rank p<0.001), but not in patients with HN (54.2% vs. 58.7% for no-HC, log-rank p=0.879, p for interaction=0.003). In a multiple Cox proportional hazard analysis, HC without HN conferred a significant event-free survival benefit (hazard ratio: 0.703, 95% confidence interval 0.542-0.912, p=0.008) over no-HC with HN., Conclusions: Only HC occurring in ADHF without HN was associated with improved clinical outcomes. These results provide further support for the importance of HN as a challenging therapeutic target in ADHF patients., (Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Heart transplantation (HTx) is the effective way to improve quality of life as well as survival in terminal heart failure (HF) patients. Since the first heart transplant in 1968 in Japan and in earnest in 1987 at Taiwan, HTx has been continuously increasing in Asia. Although the current percentage of heart transplants from Asia comprises only 5.7% of cases in the International Society of Heart and Lung Transplantation (ISHLT) registry, the values were under-reported and soon will be greatly increased. HTx in Asia shows comparable with or even better results compared with ISHLT registry data. Several endemic infections, including type B hepatitis, tuberculosis, and cytomegalovirus, are unique aspects of HTx in Asia, and need special attention in transplant care. Although cardiac allograft vasculopathy (CAV) is considered as a leading cause of death after HTx globally, multiple observations suggest less prevalence and benign nature of CAV among Asian populations. Although there are many obstacles such as religion, social taboo or legal process, Asian countries will keep overcoming obstacles and broaden the field of HTx.

Background: Acute heart failure (AHF), a common and growing health concern worldwide, is associated with high risk of post-discharge rehospitalization and mortality. Existing evidence indicates potential therapeutic benefits of serelaxin in Caucasian AHF patients, but corresponding data in Asians remain scarce. RELAX-AHF-ASIA, a multinational, randomized, double-blind, placebo-controlled, phase III trial, will evaluate the effects of serelaxin on symptom relief and clinical outcomes in Asian AHF patients, with the use of novel assessments., Methods and Results: Patients with AHF, systolic blood pressure ≥125 mm Hg, and mild to moderate renal dysfunction will be randomized within 16 hours of presentation to receive 48-hour intravenous infusion of 30 µg ⋅ kg -1 ⋅ d -1 serelaxin or placebo in addition to standard therapy. The composite primary end point includes: (1) treatment success (moderate/marked improvement in patient-reported dyspnea and physician-assessed signs of congestion on day 2); (2) treatment failure (in-hospital worsening of signs and/or symptoms of heart failure [HF] requiring intensification of intravenous HF therapy or mechanical ventilation, renal/circulatory support, rehospitalization due to HF/renal-failure, or death through day 5); and (3) unchanged status. Secondary end points include time to in-hospital worsening HF through day 5 and all-cause and cardiovascular deaths through day 180., Conclusions: RELAX-AHF-ASIA, the largest randomized clinical trial in Asian AHF patients to date, has a novel composite primary end point and the potential to become a hallmark of AHF trials., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Plasma level of N-terminal-pro-brain natriuretic peptide (NT-proBNP) is a reliable prognostic factor in patients with heart failure (HF). However, it is unclear how differently the biomarker predicts adverse outcomes in HF with preserved EF (HFpEF) versus HF with reduced EF (HFrEF)., Methods: From the Korean Heart Failure registry, a prospective multicentre cohort for consecutive patients who were hospitalised for acute HF syndrome, those with available NT-proBNP and LVEF measurements were extracted. Patients with LVEF ≥50% were categorised as the HFpEF group (N=528) and those with ≤40% as the HFrEF group (N=1142)., Results: Patients with HFpEF had significantly lower NT-proBNP level than those with HFrEF (median 2723 vs 5644 ng/L, p<0.001). Event-free survival did not differ between the two groups either in terms of death from any cause (88.4% vs 86.9%; p=0.471) or the composite of death or HF readmission at 1 year (73.8% vs 70.6%; p=0.225). High levels of NT-proBNP were significantly associated with poor outcomes. However, the relationship was not different among the HFpEF and HFrEF groups (interaction p=0.956 for all-cause death; p=0.351 for the composite of all-cause death or HF hospitalisation)., Conclusions: Plasma level of NT-proBNP is the most powerful prognostic factor in both HFpEF and HFrEF. Although patients with HFpEF have lower NT-proBNP levels, the prognosis of a patient with HFpEF expected from a given NT-proBNP level is similar with his/her counterpart with HFrEF., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Aims: In acute heart failure (AHF) patients, pulmonary oedema and low tissue perfusion may lead to changes in the acid-base balance, which may be associated with worse outcomes., Methods and Results: In this prospective nationwide cohort study from 24 academic hospitals, arterial blood gas (ABG) was measured in 1982 AHF patients at hospital admission. Acidosis was defined as pH <7.36, and alkalosis as pH >7.44. Mortality was stratified according to ABG results. Overall, 19% had acidosis, 37% had normal pH, and 44% had alkalosis. The most common type of acidosis was the mixed type (42%) followed by metabolic acidosis (40%), and the most common type of alkalosis was respiratory alkalosis (58%). At 12 months' follow-up 304 patients (15%) died. Patients with acidosis had higher mortality (acidosis 19.5%, neutral pH 13.7%, alkalosis 14.9%; P = 0.007). In the Cox proportional-hazards regression model, acidosis was a significant predictor of mortality (hazard ratio 1.93; 95% confidence intervals 1.27-2.93) along with N-terminal pro-brain type natriuretic peptide (NT-proBNP), among others. In contrast, alkalosis was not associated with increased mortality. pH had an incremental prognostic value over NT-proBNP (net reclassification improvement 30%; P < 0.001), and ABG analysis identified extra patients at increased risk for mortality among patients with an NT-proBNP level less than the median (12-month mortality 17.5% vs. 9.9%; P = 0.009)., Conclusion: In high-risk AHF patients, the most common acid-base imbalance is respiratory alkalosis. Acidosis is observed in every fifth patient and is a significant predictor of mortality. pH provides an additional prognostic value and may be used to optimize risk stratification in high-risk AHF patients., (© 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology.)

Backgrounds: We investigated the relationship between spironolactone use and all-cause mortality in acute decompensated heart failure (ADHF) patients with severe renal dysfunction. The clinical benefit of spironolactone in the treatment of heart failure (HF) has been described in several large randomized clinical trials. However, its clinical benefits have not been studied in hospitalized ADHF patients with severe renal dysfunction (estimated glomerular filtration rate [eGFR] <45 mL/min per 1.73 m(2))., Methods and Results: We retrospectively analyzed data from the Korean Heart Failure Registry. We included 1,035 ADHF patients with severe renal dysfunction. In Kaplan-Meier survival analysis, all-cause mortality in the spironolactone-treated group was significantly lower than that in the nonspironolactone group (18.1% vs 24.9%, respectively, log rank P = .028). However, spironolactone use was not an independent predictor after adjusting other HF risk factors (hazard ratio 0.974, 95% CI 0.681-1.392, P = .884) and after propensity score matching (P = .115). In subgroup analysis, the clinical benefit of spironolactone use was preserved in women, prehospital spironolactone use, the chronic kidney disease stage 3b (eGFR 30-44 mL/min per 1.73 m(2)), and the appropriate spironolactone use (eGFR ≥30 mL/min per 1.73 m(2) and K ≤5.0 mmol/L)., Conclusion: The spironolactone therapy was not beneficial in ADHF patients with severe renal dysfunction after multivariable adjusting and propensity score matching. However, we reassured the current HF guidelines for spironolactone use and the clinical benefit in chronic kidney disease stage 3b should be assessed in future clinical trial., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: The Korean Acute Heart Failure registry (KorAHF) aims to evaluate the clinical characteristics, management, hospital course, and long-term outcomes of patients hospitalized for acute heart failure syndrome (AHFS) in Korea., Methods and Results: This is a prospective observational multicentre cohort study funded by the Korea National Institute of Health. Patients hospitalized for AHFS in 10 tertiary university hospitals across the country have been consecutively enrolled since March 2011. The study is expected to complete the scheduled enrolment of 5000 patients some time in 2014, and follow-up is planned through 2016. As of April 2012, the interim analysis of 2066 consecutive subjects was performed to understand the baseline characteristics of the population. The mean age was 69 ± 14 years; 55% were male; and 50% were de novo heart failure. The mean left ventricular ejection fraction (LVEF) was 40 ± 18%. Ischaemia was both the leading cause (38%) and the most frequent aggravating factor (26%) of AHFS. ACE inhibitors/ARBs and beta-blockers were prescribed at discharge in 65% and 51% of the patients, respectively. In-hospital mortality was 5.2%, and 0.9% of patients received urgent heart transplantation. Low blood pressure and azotaemia were the most important predictors of in-hospital mortality. The post-discharge 30-day and 180-day all-cause mortality were 1.2% and 9.2%, respectively., Conclusions: Our analysis reveals that the prognosis of AHFS in Korea is poor and that there are specific features, including lower blood pressures at admission and lower rates of heart failure related to hypertension, compared with other registries. Adherence to current guidelines should be improved., (© 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.)

Heart failure (HF) complicating acute myocardial infarction (AMI) is common and is associated with poor clinical outcome. Limited data exist regarding the incidence and in-hospital mortality of AMI with HF (AMI-HF). We retrospectively analyzed 1,427 consecutive patients with AMI in the five major university hospitals in Korea at two time points, 1998 (n = 608) and 2008 (n = 819). Two hundred twenty eight patients (37.5%) in 1998 and 324 patients (39.5%) in 2008 of AMI patients complicated with HF (P = 0.429). AMI-HF patients in 2008 were older, had more hypertension, previous AMI, and lower systolic blood pressure than those in 1998. Regarding treatments, AMI-HF patients in 2008 received more revascularization procedures, more evidence based medical treatment and adjuvant therapy, such as mechanical ventilators, intra-aortic balloon pulsation compared to those in 1998. However, overall in-hospital mortality rates (6.4% vs 11.1%, P = 0.071) of AMI-HF patients were unchanged and still high even after propensity score matching analysis, irrespective of types of AMI and revascularization methods. In conclusion, more evidence-based medical and advanced procedural managements were applied for patients with AMI-HF in 2008 than in 1998. However the incidence and in-hospital mortality of AMI-HF patients were not significantly changed between the two time points.

The neurohumoral and inflammatory pathways are regarded as the main mechanisms for the progression of heart failure. We sought to investigate the prognostic value of high-sensitivity C-reactive protein (hs-CRP) and N-terminal probrain natriuretic peptide (NT-proBNP) by evaluating their relation with 12-month mortality rate in this prospective cohort study from 24 academic hospitals in Korea. In 1,608 patients with acute heart failure (AHF), the median hs-CRP and NT-proBNP values were 0.77 mg/dl (interquartile range 0.29 to 2.84) and 4,638 pg/ml (interquartile range 1,945 to 10,852), respectively. During the 12-month follow-up, 213 patients (13.3%) died. The mortality rate increased from the lowest to the highest hs-CRP quartiles (Q1 7.4%, Q2 9.5%, Q3 16.9%, Q4 19.3%, p <0.001) and NT-proBNP quartiles (Q1 7.0%, Q2 13.4%, Q3 11.6%, Q4 20.4%, p <0.001). After adjustment, both hs-CRP (hazard ratio [HR] 1.811, 95% confidence interval [CI] 1.138 to 2.882) and NT-proBNP (HR 1.971, 95% CI 1.219 to 3.187) were independent predictors of 12-month mortality among others. When combining both hs-CRP and NT-proBNP and stratifying the patients according to their median values, patients with elevation of both hs-CRP and NT-proBNP values had 2.4-fold increased hazards (HR 2.382, 95% CI 1.509 to 3.761) compared with those without elevation of both markers. In Korean patients with AHF, patients with increased levels of both hs-CRP and NT-proBNP had worse clinical outcomes. The combination of the neurohumoral and inflammatory markers may provide a better strategy for risk stratification of Asian patients with AHF., (Copyright © 2014 Elsevier Inc. All rights reserved.)