This study aimed to develop and validate deep-learning-based artificial intelligence algorithm for predicting mortality of AHF (DAHF).
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).
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.
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.
Targeting the molecular pathways underlying the cardiotoxicity associated with thoracic irradiation and doxorubicin (Dox) could reduce the morbidity and mortality associated with these anticancer ...treatments. Here, we find that vascular endothelial cells (ECs) with persistent DNA damage induced by irradiation and Dox treatment exhibit a fibrotic phenotype (endothelial-mesenchymal transition, EndMT) correlating with the colocalization of L1CAM and persistent DNA damage foci. We demonstrate that treatment with the anti-L1CAM antibody Ab417 decreases L1CAM overexpression and nuclear translocation and persistent DNA damage foci. We show that in whole-heart-irradiated mice, EC-specific p53 deletion increases vascular fibrosis and the colocalization of L1CAM and DNA damage foci, while Ab417 attenuates these effects. We also demonstrate that Ab417 prevents cardiac dysfunction-related decrease in fractional shortening and prolongs survival after whole-heart irradiation or Dox treatment. We show that cardiomyopathy patient-derived cardiovascular ECs with persistent DNA damage show upregulated L1CAM and EndMT, indicating clinical applicability of Ab417. We conclude that controlling vascular DNA damage by inhibiting nuclear L1CAM translocation might effectively prevent anticancer therapy-associated cardiotoxicity.
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.
This Korean nationwide, multicenter, noninterventional, prospective cohort study aimed to analyze physician adherence to guideline-recommended therapy for heart failure (HF) with reduced ejection ...fraction (HFrEF) and its effect on patient-reported outcomes (PROs). Patients diagnosed with or hospitalized for HFrEF within the previous year were enrolled. Treatment adherence was considered optimal when all 3 categories of guideline-recommended medications (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or angiotensin receptor-neprilysin inhibitors; beta-blockers; and mineralocorticoid receptor antagonists) were prescribed and suboptimal when ≤ 2 categories were prescribed. The 36-Item Short Form Survey (SF-36) scores were compared at baseline and 6 months between the 2 groups. Overall, 854 patients from 30 hospitals were included. At baseline, the optimal adherence group comprised 527 patients (61.7%), whereas during follow-up, the optimal and suboptimal adherence groups comprised 462 (54.1%) and 281 (32.9%) patients, respectively. Patients in the suboptimal adherence group were older, with a lower body mass index, and increased comorbidities, including renal dysfunction. SF-36 scores were significantly higher in the optimal adherence group for most domains (P < 0.05). This study showed satisfactory physician adherence to contemporary treatment for HFrEF. Optimal adherence to HF medication significantly correlated with better PROs.
The need for lightweight materials has been an important issue in automotive industries to reduce greenhouse gas emission and to improve fuel efficiency. In addition, automotive steels require an ...excellent combination of strength and ductility to sustain automotive structures and to achieve complex shapes, but the traditional approach to obtain a reduction in weight from down-gauged steels with high strength has many limitations. Here, we present a new ferrite–austenite duplex lightweight steel containing a low-density element, Al; this steel exhibits tensile elongation up to 77% as well as high tensile strength (734MPa). The enhanced properties are attributed to the simultaneous formation of deformation-induced martensites and deformation twins and the additional plasticity due to deformation twinning in austenite grains having optimal mechanical stability. The present work gives a promise for automotive applications requiring excellent properties as well as reduced specific weight.
ObjectiveThere 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%).MethodsBetween 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.ResultsIn 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%), HRadj 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%), HRadj 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%), HRadj 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%), HRadj 0.70, 95% CI 0.52 to 0.96, p=0.02).ConclusionsHFpEF 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.
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.
Vascular calcification (VC) is often associated with cardiovascular and metabolic diseases. However, the molecular mechanisms linking VC to these diseases have yet to be elucidated. Here we report ...that MDM2-induced ubiquitination of histone deacetylase 1 (HDAC1) mediates VC. Loss of HDAC1 activity via either chemical inhibitor or genetic ablation enhances VC. HDAC1 protein, but not mRNA, is reduced in cell and animal calcification models and in human calcified coronary artery. Under calcification-inducing conditions, proteasomal degradation of HDAC1 precedes VC and it is mediated by MDM2 E3 ubiquitin ligase that initiates HDAC1 K74 ubiquitination. Overexpression of MDM2 enhances VC, whereas loss of MDM2 blunts it. Decoy peptide spanning HDAC1 K74 and RG 7112, an MDM2 inhibitor, prevent VC in vivo and in vitro. These results uncover a previously unappreciated ubiquitination pathway and suggest MDM2-mediated HDAC1 ubiquitination as a new therapeutic target in VC.
•The risk of 30-day heart failure (HF) readmission or death can be estimated with 12 variables.•The risk for short-term HF-specific readmission or death can be calculated easily.•The model has the ...potential to reduce readmission by identifying high-risk patients.•The risk model can be utilized to guide suitable interventions or care in patients.
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.
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.
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 (χ2=8.540, p=0.3826).
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.