Novel symmetry-preserving neural network model for phylogenetic inference.

Motivation: Scientists world-wide are putting together massive efforts to understand how the biodiversity that we see on Earth evolved from single-cell organisms at the origin of life and this diversification process is represented through the Tree of Life. Low sampling rates and high heterogeneity in the rate of evolution across sites and lineages produce a phenomenon denoted "long branch attraction" (LBA) in which long nonsister lineages are estimated to be sisters regardless of their true evolutionary relationship. LBA has been a pervasive problem in phylogenetic inference affecting different types of methodologies from distance-based to likelihood-based. Results: Here, we present a novel neural network model that outperforms standard phylogenetic methods and other neural network implementations under LBA settings. Furthermore, unlike existing neural network models in phylogenetics, our model naturally accounts for the tree isomorphisms via permutation invariant functions which ultimately result in lower memory and allows the seamless extension to larger trees. Availability and implementation: We implement our novel theory on an open-source publicly available GitHub repository: https://github.com/crsl4/nn-phylogenetics.

Dyssynchronous heart failure models in canines: New insights into electrocardiographic, echocardiographic and histological features.

BACKGROUND: We investigated the similarities and differences between two experimental approaches using tachy-pacing technology to induce desynchronized heart failure in canines. METHODS: A total of eight dogs were included in the experiment, four were tachy-paced in right ventricle apex (RVAP) and 4 were paced in right atrium after the ablation of left bundle branch to achieve left bundle branch block (RAP+LBBB). Three weeks of follow-up were conducted to observe the changes in cardiac function and myocardial staining was performed at the end of the experiment. RESULTS: Both experimental approaches successfully established heart failure with reduced ejection fraction models, with similar trends in declining cardiac function. The RAP+LBBB group exhibited a prolonged overall ventricular activation time, delayed left ventricular activation, and lesser impact on the right ventricle. The RVAP approach led to a reduction in overall right ventricular compliance and right ventricular enlargement. The RAP+LBBB group exhibited significant reductions in left heart compliance (LVGLS, %: RAP+LBBB -12.60 ± 0.12 to -5.93 ± 1.25; RVAP -13.28 ± 0.62 to -8.05 ± 0.63, p = 0.023; LASct, %: RAP+LBBB -15.75 ± 6.85 to -1.50 ± 1.00; RVAP -15.75 ± 2.87 to -10.05 ± 6.16, p = 0.035). Histological examination revealed more pronounced fibrosis in the left ventricular wall and left atrium in the RAP+LBBB group while the RVAP group showed more prominent fibrosis in the right ventricular myocardium. CONCLUSION: Both approaches establish HFrEF models with comparable trends. The RVAP group shows impaired right ventricular function, while the RAP+LBBB group exhibits more severe decreased compliance and fibrosis in left ventricle.

Metabolomics Profiling Predicts Ventricular Arrhythmia in Patients with an Implantable Cardioverter Defibrillator.

Implantable cardioverter defibrillators (ICDs) reduce sudden cardiac death (SCD) when patients experience life-threatening ventricular arrhythmias (LTVA). However, current strategies determining ICD patient selection and risk stratification are inefficient. We used metabolomics to assess whether dysregulated metabolites are associated with LTVA and identify potential biomarkers. Baseline plasma samples were collected from 72 patients receiving ICDs. Over a median follow-up of 524.0 days (range 239.0-705.5), LTVA occurred in 23 (31.9%) patients (22 effective ICD treatments and 1 SCD). After confounding risk factors adjustment for age, smoking, secondary prevention, and creatine kinase MB, 23 metabolites were significantly associated with LTVA. Pathway analysis revealed LTVA associations with disrupted metabolism of glycine, serine, threonine, and branched chain amino acids. Pathway enrichment analysis identified a panel of 6 metabolites that potentially predicted LTVA, with an area under the receiver operating characteristic curve of 0.8. Future studies are necessary on biological mechanisms and potential clinical use.

Grey correlation analysis on influencing factors of Yang deficiency constitution / 数字中医药（英文）

@#【Objective 】 To explore the influencing factors of Yang deficiency constitution in traditional Chinese medicine (TCM) from the perspective of mathematics with the use of calculation formulas, so as to protect patients from getting diseases caused by Yang deficiency constitution and provide suggestions for TCM disease prevention. 【Methods】  Based on the classification and determination criteria of TCM constitution implemented by China Association of Chinese Medicine, data for 24 solar terms from May 5, 2020(Start of Summer) to April 20, 2021 (Grain Rain) for the identification of Yang deficiency were collected by mobile constitution identification system. The grey correlation analysis method was used to determine the grey correlation degree of the factors influencing Yang deficiency constitution. In addition, a random forest model was constructed for the verification of the results from the grey correlation analysis, and for the evaluation of correlation degree between Yang deficiency constitution and its influencing factors. 【Results】  A total of 16 259 sets of data were collected from healthy or sub-healthy individuals aged from 18 to 60 years living in the central and northeastern parts of Sichuan Province(China) for the identification of TCM constitutions. After screening and preprocessing, a total of 544 sets of data for the identification of Yang deficiency constitution, involving 18 aspects of factors influencing Yang deficiency constitution. The results of the grey correlation analysis showed that there were 12 influencing factors whose grey correlation degree with Yang deficiency constitution was greater than 0.6. The accuracy of these 12 influencing factors with the training set and validation set of the Yang deficiency constitution random forest model were 98.39% and 93.12%, respectively. 【Conclusion】  In the sample data selected in this paper, grey correlation analysis is the appropriate technology to analyze the influencing factors of Yang deficiency constitution. It provides a new idea and a new methodological reference for the research and analysis of the influencing factors of TCM constitution.

Left Bundle Branch Area Pacing versus Biventricular Pacing for Cardiac Resynchronization Therapy on Morbidity and Mortality.

BACKGROUND: Left bundle branch area pacing (LBBAP) has emerged as an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT). We aimed to compare the morbidity and mortality associated with LBBAP versus BVP in patients undergoing CRT implantation. METHODS: Consecutive patients who received CRT from two high-volume implantation centers were retrospectively recruited. The primary endpoint was a composite of all-cause death and heart failure hospitalization, and the secondary endpoint was all-cause death. RESULTS: A total of 491 patients receiving CRT (154 via LBBAP and 337 via BVP) were included, with a median follow-up of 31 months. The primary endpoint was reached by 21 (13.6%) patients in the LBBAP group, as compared with 74 (22.0%) patients in the BVP group [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.43-1.14, P = 0.15]. There were 10 (6.5%) deaths in the LBBAP group, as compared with 31 (9.2%) in the BVP group (HR 0.91, 95% CI 0.44-1.86, P = 0.79). No significant difference was observed in the risk of either the primary or secondary endpoint between LBBAP and BVP after multivariate Cox regression (HR 0.74, 95% CI 0.45-1.23, P = 0.24, and HR 0.77, 95% CI 0.36-1.67, P = 0.51, respectively) or propensity score matching (HR 0.72, 95% CI 0.41-1.29, P = 0.28, and HR 0.69, 95% CI 0.29-1.65, P = 0.40, respectively). CONCLUSION: LBBAP was associated with a comparable effect on morbidity and mortality relative to BVP in patients with indications for CRT.

Transition structures for the oxy-ene reaction.

An overlooked pericyclic reaction between allyl alcohols and alkenes to form carbonyl compounds is analyzed. It combines the characteristic features of the Alder-ene reaction and of the oxy-Cope rearrangement. This oxy-ene reaction could be involved in biosynthetic pathways.

Cationic-palladium catalyzed regio- and stereoselective syn-1,2-dicarbofunctionalization of unsymmetrical internal alkynes.

π-Extended tetrasubstituted olefins are widely found motifs in natural products, leading drugs, and agrochemicals. Thus, development of modular strategies for the synthesis of complex all-carbon-substituted olefins always draws attention. The difunctionalization of unsymmetrical alkynes is an attractive approach but it has remained faced with regioselectivity issues. Here we report the discovery of a regio- and stereoselective syn-1,2-dicarbofunctionalization of unsymmetrical internal alkynes. A cationic Pd-catalyzed three-component coupling of aryl diazonium salts, aryl boronic acids (or olefins) and yne-acetates enables access to all-carbon substituted unsymmetrical olefins. The transformation features broad scope with labile functional group tolerance, building broad chemical space of structural diversity (94 molecules). The value of this synthetic method is demonstrated by the direct transformation of natural products and drug candidates containing yne-acetates, to enable highly substituted structurally complex allyl acetate analogues of biologically important compounds. Synthetic versatility of the carboxylate bearing highly substituted olefins is also presented. The reaction outcome is attributed to the in situ formation of stabilized cationic aryl-Pd species, which regulates regioselective aryl-palladation of unsymmetrical yne-acetates. Control experiments reveal the synergy between the carboxylate protecting group and the cationic Pd-intermediate in the regioselectivity and reaction productivity; density functional theory (DFT) studies rationalize the selectivity of the reaction.

Palladium-Catalyzed Regioselective Arylalkenylation of Ynamides.

A cationic palladium-catalyzed arylalkenylation of ynamides is presented. The putative keteniminium arylpalladium intermediate likely dictates the regioselective carbopalladation of the ynamide to form a vinylpalladium species. The capture of this complex by the olefin yields linear conjugated ß-alkenyl aminodienes (especially with trans selectivity). The transformation features a broad scope with labile functional group tolerance and makes 42 unusual molecular scaffolds with structural diversity. DFT studies provide valuable insights into the reaction mechanism.

Screening influencing factors of blood stasis constitution in traditional Chinese medicine / 数字中医药（英文）

@#Objective To study the influencing factors of blood stasis constitution and provide a basis for treating blood stasis-related diseases by traditional Chinese medicine (TCM) constitution identification. Methods Data were collected using the self-developed TCM constitution identification platform based on B/S model by the project team. The obtained data were divided into blood stasis constitution and normal constitution groups. The differences of the categorical type influencing factors (gender, birth mode, feeding mode within four months of birth, family history, marital status, eating habits, sleeping habits, exercise habits, emotional state, stress situation, and living environment) and the quantitative type influencing factors (sleep time, age, and mother's age at birth) on the constitution of the two groups were analyzed. In the single-factor analysis, the Pearson's chi-square test was selected for the categorical variable, and the independent sample t test and Mann-Whitney U nonparametric test were selected for the quantitative variables according to whether they conformed to the positive-terrestrial distribution; the binary logistic stepwise regression method was selected for the multi-factor analysis. Results The data of 318 cases were collected from the TCM composition identification platform, and 159 cases of blood stasis constitution were used as the experimental group and 159 cases of normal constitution were used as the control group. The Pearson's chi-square test yielded significant differences (P < 0.05) in the effects of gender, pressure situation, family history, living environment, emotional state, exercise habits, and dietary habits on blood stasis constitution. The independent samples t test yielded differences in sleep duration between the blood stasis constitution and normal constitution populations (P < 0.05), which meant sleep duration of the blood stasis constitution population was less than that of the normal constitution population. The Mann-Whitney U nonparametric test results accepted the original hypothesis that there was no difference in the distribution of age and mother’s age at birth across constitution types (P > 0.05). Binary logistic regression analysis showed that gender, family history, marital status, living environment, exercise habits, and emotional state were risk factors for blood stasis constitution (P < 0.05). Conclusion Gender, family history, living environment, emotional state, and exercise habits were significant influencing factors of blood stasis constitution. Blood stasis constitution populations can pay more attention to these influencing factors in their daily life for the prevention and reconciliation of blood stasis constitution.

Yb(iii)-catalysed syn-thioallylation of ynamides.

Reported herein is a syn-thioallylation of ynamides incorporating a sulfide moiety at the α-position and an allyl group at the ß-position of the ynamide. The transformation is successful under ytterbium(iii)-catalysis, providing access to highly substituted thioamino-skipped-dienes with broad substrate scope. Thus, tetrasubstituted olefins (with four different functional groups: amide, phenyl, thioaryl/alkyl, and allyl on the carbon centers) are made in a single step from readily accessible ynamides, preserving complete atom economy. The reaction can be extended to the synthesis of selenoamino dienes by ynamide syn-selenoallylation. DFT studies and control experiments provide insight into the reaction mechanism.

Machine learning-based long-term outcome prediction in patients undergoing percutaneous coronary intervention.

BACKGROUND: Traditional prognostic risk assessment in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) is based on a limited selection of clinical and imaging findings. Machine learning (ML) can consider a higher number and complexity of variables and may be useful for characterising cardiovascular risk, predicting outcomes, and identifying biomarkers in large population studies. METHODS: We prospectively enrolled 9,680 consecutive patients with coronary artery disease who underwent PCI at our institution between January 2013 and December 2013. Clinical features were selected and used to train 6 different ML models (support vector machine, decision tree, random forest, gradient boosting decision tree, neural network, and logistic regression) to predict cardiovascular outcomes, 10-fold cross-validation to evaluate the performance of models. RESULTS: During the 5-year follow-up, 467 (4.82%) patients died. Eighty-seven risk baseline measurements were used to train ML models. Compared with the other models, the random forest model (RF-PCI) exhibited the best performance on predicting all-cause mortality (area under the receiver operating characteristic curve: 0.71±0.04). Calibration plots demonstrated a slight overprediction for patients using the RF-PCI model (Hosmer-Lemeshow test: P>0.05). The top 15 features related to PCI candidates' long-term prognosis, among which 11 were laboratory measures. CONCLUSIONS: ML models improved the prediction of long-term all-cause mortality in patients with coronary artery disease before PCI. The performance of the RF model was better than that of the other models, providing a meaningful stratification.

DFT Analysis into the Calcium(II)-Catalyzed Coupling of Alcohols With Vinylboronic Acids: Cooperativity of Two Different Lewis Acids and Counterion Effects.

The mechanism of the calcium-catalyzed coupling of alcohols with vinylboronic acids has been analyzed by means of density functional theory computations. This study reveals that the calcium and boron Lewis acids associate to form a superelectrophile able to promote a pericyclic group transfer reaction with allyl alcohols. With other alcohols, the two Lewis acids act synergistically to activate the OH functionality and trigger a SNi reaction pathway. These two mechanisms are affected by the nature of the counterions, which has been rationalized by electronic and steric factors.

Global and regional cardiac dysfunction quantified by 18F-FDG PET scans can predict ventricular arrhythmia in patients with implantable cardioverter defibrillator.

BACKGROUND: A low appropriate therapy rate indicates that a minority of patients will benefit from their implantable cardioverter defibrillator (ICD). Quantitative measurements from 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) may predict ventricular arrhythmia (VA) occurrence after ICD placement. METHODS: We performed a prospective observational study and recruited patients who required ICD placement. Pre-procedure image scans were performed. Patients were followed up for VA occurrence. Associations between image results and VA were analyzed. RESULTS: In 51 patients (33 males, 53.9 ± 17.2 years) analyzed, 17 (33.3%) developed VA. Compared with patients without VA, patients with VA had significantly larger values in scar area (17.7 ± 12.4% vs. 7.0 ± 7.9%), phase standard deviation (51.4° ± 14.0° vs. 34.0° ± 15.0°), bandwidth (172.9° ± 39.8° vs. 128.7° ± 49.9°), sum thickening score (STS, 29.5 ± 11.1 vs. 17.8 ± 13.2), and sum motion score (42.9 ± 11.5 vs. 33.0 ± 19.0). Cox regression analysis and receiver operating characteristic curve analysis showed that scar size, dyssynchrony, and STS were associated with VA occurrence (HR, 4.956, 95% CI 1.70-14.46). CONCLUSION: Larger left ventricular scar burden, increased dyssynchrony, and higher STS quantified by 18F-FDG PET may indicate a higher VA incidence after ICD placement.

Alkynophilicity of Group 13 MX3 Salts: A Theoretical Study.

The concept of alkynophilicity is revisited with group 13 MX3 metal salts (M = In, Ga, Al, B; X = Cl, OTf) using M06-2X/6-31+G(d,p) calculations. This study aims at answering why some of these salts show reactivity toward enynes that is similar to that observed with late-transition-metal complexes, notably Au(I) species, and why some of them are inactive. For this purpose, the mechanism of the skeletal reorganization of 1,6-enynes into 1-vinylcyclopentenes has been computed, including monomeric ("standard") and dimeric (superelectrophilic) activation. Those results are confronted with deactivation pathways based on the dissociation of the M-X bond. The role of the X ligand in the stabilization of the intermediate nonclassical carbocation is revealed, and the whole features required to make a good π-Lewis acid are discussed.

Validation of Three European Risk Scores to Predict Long-Term Outcomes for Patients Receiving Cardiac Resynchronization Therapy in an Asian Population.

To validate externally and recalibrate three European risk scores for all-cause mortality and transplantation in patients receiving cardiac resynchronization therapy (CRT) in an Asian population. Data were collected at our institution between January 2010 and December 2017. The primary endpoints were all-cause mortality and heart transplantation. Of the 506 patients who were followed for 2 years, 104 reached the primary endpoint. The Kaplan-Meier event-free survival analysis, stratified according to the three scores, yielded significant results (log-rank test, all P < 0.05), with a good fit between the predicted and observed event rates (Hosmer-Lemeshow goodness-of-fit test, all P > 0.05). The ScREEN score yielded the best discriminatory power for the primary endpoints compared with the VALID-CRT and EAARN scores. ScREEN was the best predictor of all-cause mortality and heart transplantation. Risk scores based on different populations should be selected cautiously. Graphical Abstract.

Elevated resting heart rates are a risk factor for mortality among patients with coronavirus disease 2019 in Wuhan, China.

BACKGROUND: We evaluated the association between higher resting heart rates (RHRs) and adverse events in COVID-19 patients. METHODS: One hundred and thirty-six patients with laboratory-confirmed COVID-19 were admitted. Outcomes of patients with different RHRs were compared. RESULTS: Twenty-nine patients had RHRs of <80 bpm (beat per min), 85 had 80-99 bpm and 22 had ≥100 bpm as tachycardia. Those with higher RHRs had lower pulse oxygen saturation (SpO2) and higher temperatures, and there was a higher proportion of men upon admission (all P < 0.05). Patients with higher RHRs showed higher white blood cell counts and D-dimer, cardiac troponin I (TnI), N-terminal pro-B-type natriuretic peptide and hypersensitive C-reactive protein levels, but lower albumin levels (all P < 0.05) after admission. During follow-up, 26 patients died (mortality rate, 19.1%). The mortality rate was significantly higher among patients with tachycardia than among the moderate and low RHR groups (all P < 0.001). Kaplan-Meier survival curves showed that the risks of death and ventilation use increased for patients with tachycardia (P < 0.001). Elevated RHR as a continuous variable and a mean RHR as tachycardia were independent risk factors for mortality and ventilator use (all P < 0.05) in the multivariable adjusted Cox proportional hazards regression model. CONCLUSIONS: Elevated average RHRs during the first 3 days of hospitalisation were associated with adverse outcomes in COVID-19 patients. Average RHRs as tachycardia can independently predict all-cause mortality.

Comprehensive plasma metabolites profiling reveals phosphatidylcholine species as potential predictors for cardiac resynchronization therapy response.

AIMS: This study aimed to identify the plasma metabolite fingerprint in patients with heart failure and to develop a prediction tool based on differential metabolites for predicting the response to cardiac resynchronization therapy (CRT). METHODS AND RESULTS: We prospectively recruited 32 healthy individuals and 42 consecutive patients with HF who underwent CRT between January 2018 and January 2019. Peripheral venous blood samples, clinical data, and echocardiographic signatures were collected before CRT implantation. Liquid chromatography-mass spectrometry was used to perform untargeted metabolites profiling for peripheral plasma under ESI+ and ESI- modes. After 6 month follow-up, patients were categorized as CRT responders or non-responders based on the alterations of echocardiographic characteristics. Compared with healthy individuals, patients with HF had distinct metabolomic profiles under both ESI+ and ESI- modes, featuring increased free fatty acids, carnitine, ß-hydroxybutyrate, and dysregulated lipids with heterogeneous alterations such as phosphatidylcholines (PCs) and sphingomyelins. Disparities of baseline metabolomics profile were observed between CRT responders and non-responders under ESI+ mode but not under ESI- mode. Further metabolites analysis revealed that a group of 20 PCs metabolites under ESI+ mode were major contributors to the distinct profiles between the two groups. We utilized LASSO regression model and identified a panel of four PCs metabolites [including PC (20:0/18:4), PC (20:4/20:0), PC 40:4, and PC (20:4/18:0)] as major predictors for CRT response prediction. Among our whole population (n = 42), receive operating characteristics analysis revealed that the four PCs-based model could nicely discriminate the CRT responders from non-responders (area under the curve = 0.906) with a sensitivity of 83.3% and a specificity of 90.0%. Cross-validation analysis also showed a satisfactory and robust performance of the model with the area under the curve of 0.910 in the training dataset and 0.880 in the testing dataset. CONCLUSIONS: Patients with HF held significantly altered plasma metabolomics profile compared with the healthy individuals. Within the HF group, the non-responders had a distinct plasma metabolomics profile in contrast to the responders to CRT, which was characterized by increased PCs species. A novel predictive model incorporating four PCs metabolites performed well in identifying CRT non-responders. These four PCs might severe as potential biomarkers for predicting CRT response. Further validations are needed in multi-centre studies with larger external cohorts.

Plasma Metabolomic Profiles Differentiate Patients With Dilated Cardiomyopathy and Ischemic Cardiomyopathy.

Dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) are common causes of heart failure (HF). Though they share similar clinical characteristics, their differential effects on cardiovascular metabolomics have yet to be elucidated. In this study, we applied a comprehensive metabolomics platform to plasma samples of HF patients with different etiology (38 patients with DCM and 18 patients with ICM) and 20 healthy controls. Significant differences in metabolomics profiling were shown among two cardiomyopathy groups and healthy controls. Two hundred thirty three dysregulated metabolites were identified between DCM vs. healthy controls, and 204 dysregulated metabolites between ICM patients and healthy controls. They have 140 metabolites in common, with fold-changes in the same direction in both groups. Pathway analysis found the commonalities of HF pathways as well as disease-specific metabolic signatures. In addition, we found that a combination panel of 6 metabolites including 1-pyrroline-2-carboxylate, norvaline, lysophosphatidylinositol (16:0/0:0), phosphatidylglycerol (6:0/8:0), fatty acid esters of hydroxy fatty acid (24:1), and phosphatidylcholine (18:0/18:3) may have the potential to differentiate patients with DCM and ICM.

Association Between Subcutaneous Implantable Cardioverter Defibrillator Preimplantation Screening and the Response to Cardiac Resynchronization Therapy.

BACKGROUND AND OBJECTIVES: Preimplantation QRS-T morphology screening (TMS) is a composite tool for selecting subcutaneous implantable cardioverter defibrillator (S-ICD) candidates. However, its role in predicting the patient's response to cardiac resynchronization therapy (CRT) is uncertain. METHODS: A total of 55 consecutive de novo CRT candidates were enrolled between January 2016 and March 2017. Electrocardiogram (ECG) and TMS were performed before and soon after implantation. The ECG parameters were recorded, including QRS duration and morphology (such as ΔQRS_Index, QTc during biventricular pacing mode [BiV pacing QTc], and QRS/T ratio during biventricular pacing mode [BiV pacing QRS/T ratio]). TMS monitored three sensory vectors of the S-ICD. Six months after implantation, the responses to CRT were evaluated. RESULTS: Thirty-nine patients (70.9%) passed the TMS during biventricular pacing mode. At the six-month follow-up, the number of responders and super-responders was significantly higher in the passing group than in the non-passing group (responders: 31/39 [79.5%] vs. 5/16 [31.3%], p<0.001; super-responders: 9/39 [23.1%] vs. 1/16 [6.3%], p=0.020). The super-response rate was higher among patients who passed all three vectors than among those who passed 1 or 2 vectors (3 vs. 2 vectors, p=0.018; 3 vs. 1 vector, p=0.003). A smaller left atrial diameter, vectors that passed TMS during biventricular pacing mode, and larger ΔQRS_Index values were independently associated with good CRT response. CONCLUSIONS: Our study demonstrated that patients on CRT who pass the TMS during biventricular pacing mode are more likely to respond and super-respond to CRT.

A Predictive Model for Super-Response to Cardiac Resynchronization Therapy: The QQ-LAE Score.

OBJECTIVES: It is important to identify super-responders who can derive most benefits from cardiac resynchronization therapy (CRT). We aimed to establish a scoring model that can be used for predicting super-response to CRT. METHODS: We retrospectively reviewed 387 CRT patients. Multivariate logistic regression analysis was performed to identify predictors for super-response (defined as an absolute increase in left ventricular ejection fraction of ≥15% at 6-month follow-up) and to create a score model. Multivariate Cox proportional-hazard regression analysis was conducted to assess associations with the long-term endpoint (defined as cardiac death/heart transplant, heart failure (HF) hospitalization, or all-cause death) across the score categories at follow-up. RESULTS: Among 387 patients, 109 (28.2%) met super-response. In multivariable analysis, 5 independent predictors (QQ-LAE) were identified: prior no fragmented QRS (odds ratio (OR) = 3.10 (1.39, 6.94)), QRS duration ≥170 ms (OR = 2.37 (1.35, 4.12)), left bundle branch block (OR = 2.57 (1.04, 6.37)), left atrial diameter <45 mm (OR = 3.27 (1.81, 5.89)), and left ventricular end-diastolic dimension <75 mm (OR = 4.11 (1.99, 8.48)). One point was attributed to each predictor, and three score categories were identified. The proportion of super-response after 6-month CRT implantation in patients with scores 0-3, 4, and 5 was 14.6%, 40.3%, and 64.1%, respectively (P < 0.001). Patients with score 5 had an 88% reduction in the risk of cardiac death/heart transplant (P=0.042), a 71% reduction in the risk of HF hospitalization (P=0.048), and an 89% reduction in the risk of all-cause mortality (P=0.028) compared to patients with scores 0-3. CONCLUSIONS: The QQ-LAE score can be used for prediction of super-response to CRT and selection of most suitable patients in clinical practices.