The combined association of physical activity and alcohol use with long-term mortality: an age-stratified analysis.

BACKGROUND: The combined association of physical activity (PA) and alcohol use (AU) with long-term mortality is yet to be investigated. METHODS: For the current study, 12,621 participants aged ≥ 20 years were enrolled from the National Health and Nutrition Examination Survey (1999-2004). The study endpoint was all-cause mortality. Cox proportional hazards regression models were used to examine the combined effect of PA and AU on long-term mortality. RESULTS: The study population was divided into young (< 60 years, N = 8,258) and old (≥ 60 years, N = 4,363) groups. The median follow-up time was 203 months. In both young and old group, sedentary lifestyle combined with even minimal AU were associated with elevated risk of death (all P < 0.05). In young group, the integration of high volume AU with any degree of PA, including sedentary PA (HR = 2.35, 95% CI 1.24-4.44, P = 0.009), low PA (HR = 1.64, 95% CI 1.01-2.68, P = 0.047), and moderate-to-vigorous PA (HR = 1.99, 95% CI 1.03-3.84, P = 0.041), was associated with an increased risk of mortality. This relationship persisted as significant after adjusting for potential confounders (all P < 0.05). In old group, combining moderate-to-vigorous PA and low volume AU (HR = 0.59, 95% CI 0.37-0.94, P = 0.027) was associated with a reduction in mortality. After adjustment, the combination of moderate-to-vigorous PA and low volume AU was independently associated with favorable prognostic outcomes (all P < 0.05). CONCLUSIONS: In both age groups, combining sedentary lifestyle with even minimal AU was a risk factor for death. In young group, combining any level of PA with high volume AU was associated with increased mortality. In old group, combining moderate-to-vigorous PA with low volume AU was related to reduced mortality.

Association between triglyceride-glucose index and the risk of heart failure hospitalization in older diabetic patients received right ventricular pacing: a retrospective cohort study.

BACKGROUND: The prognostic value of triglyceride-glucose (TyG) index is not yet known for older diabetic patients received right ventricular pacing (RVP). We aimed to investigate the association between TyG index and the risk of heart failure hospitalization (HFH) in older diabetic patients received RVP. METHODS: This study was conducted between January 2017 and January 2018 at Fuwai Hospital, Beijing, China, and included older (age ≥ 65 years) diabetic patients that received RVP for the first time. TyG index were obtained before implantation. The primary endpoint was HFH. RESULTS: A total of 231 patients were divided into three groups according to the tertiles of TyG index: < 8.5 (T1, N = 77), 8.5-9.1 (T2, N = 77), and > 9.1 (T3, N = 77). T3 group had higher rate of HFH (Log-rank = 11.7, P = 0.003). Multivariate analyses showed that, TyG index served as an independent predictor for HFH, both as numerical variable (HR = 1.94, 95% CI 1.21-3.11, P = 0.006), and as categorical variable (HR = 2.31, 95% CI 1.09-4.89, P = 0.03). RCS demonstrated that the risk of HFH was relatively low until TyG index exceeded 8.8, beyond which the risk began to increase rapidly (P-non-linear = 0.006). CONCLUSION: Preimplantation TyG index emerges as a robust, independent predictor for HFH in older diabetic patients received RVP, and TyG index > 8.8 might be the optimal cut-off value.

Implication of geriatric nutritional risk index on treatment response and long-term prognosis in patients with cardiac resynchronization therapy.

PURPOSE: Geriatric Nutritional Risk Index (GNRI) is a simple tool for assessing the nutritional status of the aging population. This study aims to explore the clinical implication of GNRI on treatment response and long-term clinical outcomes in heart failure (HF) patients receiving cardiac resynchronization therapy (CRT). METHODS: Patients who underwent CRT implantation or upgrade at our hospital were retrospectively included. The association of GNRI and its tertiles with the echocardiographic response, all-cause mortality or heart transplantation, and the first hospitalization due to HF were investigated. RESULTS: Totally, 647 patients were enrolled, with a median age of 60 [Interquartile Range (IQR): 52-67] years and mean score of GNRI at 107.9 ± 23.7. Super-response rates increased significantly among the GNRI T1, T2, and T3 groups (25.1%, 29.8% vs. 41.1%, P = 0.002). Patients with higher GNRI were more likely to have better LVEF improvement after multiple adjustments (OR = 1.13, 95% CI: 1.04-1.23, P = 0.010). Higher GNRI was independently associated with a lower risk of all-cause mortality or heart implantation (HR = 0.95, 95% CI: 0.93-0.96, P < 0.001) and HF hospitalization (HR = 0.96, 95% CI: 0.95-0.98, P < 0.001). The inclusion of GNRI enhanced the predictability of all-cause mortality based on traditional model, including sex, New York Heart Association functional class, left bundle branch block, QRS reduction, and N-terminal pro-B-type natriuretic peptide level (C statistics improved from 0.785 to 0.813, P = 0.007). CONCLUSION: Higher GNRI was associated with better treatment response and long-term prognosis in HF patients with CRT. Evaluation of nutritional status among CRT population is necessary for individualized choice of potential responders.

Retinal vascular density as a potential biomarker of diabetic cerebral small vessel disease.

AIM: The retina and brain share similar anatomical and physiological features. Thus, retinal imaging by optical coherence tomography angiography (OCTA) might be a potential tool for the early diagnosis of diabetic cerebral small vessel disease (CSVD). In this study, we aimed to evaluate retinal vascular density (VD) in diabetic CSVD by OCTA imaging and explore the associations between retinal VD and cerebral magnetic resonance imaging (MRI) markers and cognitive function. METHODS: In total, 131 patients were enrolled, including CSVD (n = 43) and non-CSVD groups (n = 88). The VD and foveal avascular zone of the retinal capillary plexus were measured with OCTA. A brain MRI was performed. RESULTS: MRI imaging showed that in the diabetic CSVD group, white matter hyperintensities (WMHs), particularly deep WMHs (58.82%), are the most common MRI marker, followed by cerebral microbleeds in the subtentorial and cortical areas (34.78%). The CSVD group showed increases in the prevalence of cognitive dysfunction (p = .034) and depression (p = .033) and decreases in visuospatial/executive ability and delayed recall ability. In the CSVD group, VDs of the macular superficial vascular plexus (32.93 ± 7.15% vs. 36.97 ± 6.59%, p = .002), intermediate capillary plexus (20.87 ± 4.30% vs. 23.08 ± 4.30%, p = .005) and deep capillary plexus (23.54 ± 5.00% vs. 26.05 ± 4.20%, p = .003) were lower than those of the non-CSVD group. Multiple linear regression analysis showed that VD of the macular superficial vascular plexus was independently associated with cerebral microbleeds. Meanwhile, VD of the macular intermediate capillary plexus was associated with white matter lacunar infarcts after adjustment. CONCLUSIONS: Diabetic CSVDs are characterized by MRI markers, including deep WMHs and cerebral microbleeds, and showed impaired cognition with decreased visuospatial/executive ability and delayed recall ability. OCTA imaging revealed a significant decrease in retinal microvascular perfusion in diabetic CSVD, which was related to MRI markers and cognitive function. OCTA might be a valuable potential measurement for the early diagnosis of CSVD.

The value of CT-based radiomics in predicting hemorrhagic transformation in acute ischemic stroke patients without recanalization therapy.

Objective: The aim of this study is to investigate the clinical value of radiomics based on non-enhanced head CT in the prediction of hemorrhage transformation in acute ischemic stroke (AIS). Materials and methods: A total of 140 patients diagnosed with AIS from January 2015 to August 2022 were enrolled. Radiomic features from infarcted areas on non-enhanced CT images were extracted using ITK-SNAP. The max-relevance and min-redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) were used to select features. The radiomics signature was then constructed by multiple logistic regressions. The clinicoradiomics nomogram was constructed by combining radiomics signature and clinical characteristics. All predictive models were constructed in the training group, and these were verified in the validation group. All models were evaluated with the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: Of the 140 patients, 59 experienced hemorrhagic transformation, while 81 remained stable. The radiomics signature was constructed by 10 radiomics features. The clinicoradiomics nomogram was constructed by combining radiomics signature and atrial fibrillation. The area under the ROC curve (AUCs) of the clinical model, radiomics signature, and clinicoradiomics nomogram for predicting hemorrhagic transformation in the training group were 0.64, 0.86, and 0.86, respectively. The AUCs of the clinical model, radiomics signature, and clinicoradiomics nomogram for predicting hemorrhagic transformation in the validation group were 0.63, 0.90, and 0.90, respectively. The DCA curves showed that the radiomics signature performed well as well as the clinicoradiomics nomogram. The DCA curve showed that the clinical application value of the radiomics signature is similar to that of the clinicoradiomics nomogram. Conclusion: The radiomics signature, constructed without incorporating clinical characteristics, can independently and effectively predict hemorrhagic transformation in AIS patients.

Research on automatic recognition radiomics algorithm for early sacroiliac arthritis based on sacroiliac MRI imaging.

OBJECTIVE: To create an automated machine learning model using sacroiliac joint MRI imaging for early sacroiliac arthritis detection, aiming to enhance diagnostic accuracy. METHODS: We conducted a retrospective analysis involving 71 patients with early sacroiliac arthritis and 85 patients with normal sacroiliac joint MRI scans. Transverse T1WI and T2WI sequences were collected and subjected to radiomics analysis by two physicians. Patients were randomly divided into training and test groups at a 7:3 ratio. Initially, we extracted the region of interest on the sacroiliac joint surface using ITK-SNAP 3.6.0 software and extracted radiomic features. We retained features with an Intraclass Correlation Coefficient > 0.80, followed by filtering using max-relevance and min-redundancy (mRMR) and LASSO algorithms to establish an automatic identification model for sacroiliac joint surface injury. Receiver operating characteristic (ROC) curves were plotted, and the area under the ROC curve (AUC) was calculated. Model performance was assessed by accuracy, sensitivity, and specificity. RESULTS: We evaluated model performance, achieving an AUC of 0.943 for the SVM-T1WI training group, with accuracy, sensitivity, and specificity values of 0.878, 0.836, and 0.943, respectively. The SVM-T1WI test group exhibited an AUC of 0.875, with corresponding accuracy, sensitivity, and specificity values of 0.909, 0.929, and 0.875, respectively. For the SVM-T2WI training group, the AUC was 0.975, with accuracy, sensitivity, and specificity values of 0.933, 0.889, and 0.750. The SVM-T2WI test group produced an AUC of 0.902, with accuracy, sensitivity, and specificity values of 0.864, 0.889, and 0.800. In the SVM-bimodal training group, we achieved an AUC of 0.974, with accuracy, sensitivity, and specificity values of 0.921, 0.889, and 0.971, respectively. The SVM-bimodal test group exhibited an AUC of 0.964, with accuracy, sensitivity, and specificity values of 0.955, 1.000, and 0.875, respectively. CONCLUSION: The radiomics-based detection model demonstrates excellent automatic identification performance for early sacroiliitis.

Effect of short-term cardiac function changes after cardiac resynchronization therapy on long-term prognosis in heart failure patients with and without diabetes.

Background: The relationship between short-term cardiac function changes and long-term outcomes in heart failure (HF) patients undergoing cardiac resynchronization therapy (CRT) remains uncertain, especially when stratified by diabetes status. Objectives: This study aims to assess the association between short-term cardiac function changes and outcomes such as all-cause mortality and HF hospitalization in patients undergoing CRT, stratified by diabetes status. Design: This is a cohort longitudinal retrospective study. Methods: A total of 666 HF patients, treated with CRT between March 2007 and March 2019, were included in this study. Among them, 166 patients (24.9%) were diagnosed with diabetes. Cardiac function was assessed at baseline and again at 6 months, incorporating evaluations of left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left atrial diameter (LAD), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and QRS duration. The QRS duration represents the time required for a stimulus to spread through the ventricles (ventricular depolarization). The primary endpoints of the study were all-cause mortality and HF-related hospitalization. Results: During a median follow-up of 2.51 years, 172 (25.8%) patients died and 197 (29.6%) were hospitalized for HF. Changes in LVEF, LVEDD, and LAD within 6 months had similar effects on adverse outcomes in both diabetic and nondiabetic patients. However, the presence of diabetes significantly modified the association between changes in NT-proBNP and QRS duration and adverse outcomes. Short-term changes in NT-proBNP and QRS duration were positively associated with all-cause mortality and HF hospitalization in patients without diabetes. However, the relationship between short-term changes in NT-proBNP and QRS duration and adverse outcomes was non-linear in diabetic patients. Conclusion: Improvement of cardiac function after CRT implantation can reduce long-term risk of all-cause mortality and HF hospitalization in HF patients. However, the presence of diabetes may affect the association between short-term changes in NT-proBNP and QRS duration and adverse outcomes.

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.

Joint association of sedentary behavior and vitamin D status with mortality among cancer survivors.

BACKGROUND: Sedentary behavior and vitamin D deficiency are independent risk factors for mortality in cancer survivors, but their joint association with mortality has not been investigated. METHODS: We analyzed data from 2914 cancer survivors who participated in the National Health and Nutrition Examination Survey (2007-2018) and followed up with them until December 31, 2019. Sedentary behavior was assessed by self-reported daily hours of sitting, and vitamin D status was measured by serum total 25-hydroxyvitamin D (25(OH)D) levels. RESULTS: Among 2914 cancer survivors, vitamin D deficiency was more prevalent in those with prolonged daily sitting time. During up to 13.2 years (median, 5.6 years) of follow-up, there were 676 deaths (cancer, 226; cardiovascular disease, 142; other causes, 308). The prolonged sitting time was associated with a higher risk of all-cause and noncancer mortality, and vitamin D deficiency was associated with a higher risk of all-cause and cancer mortality. Furthermore, cancer survivors with both prolonged sitting time (≥ 6 h/day) and vitamin D deficiency had a significantly higher risk of all-cause (HR, 2.05; 95% CI: 1.54-2.72), cancer (HR, 2.33; 95% CI, 1.47-3.70), and noncancer mortality (HR, 1.91; 95% CI, 1.33-2.74) than those with neither risk factor after adjustment for potential confounders. CONCLUSIONS: In a nationally representative sample of U.S. cancer survivors, the joint presence of sedentary behavior and vitamin D deficiency was significantly associated with an increased risk of all-cause and cancer-specific mortality.

The effect of background elements of pictures on the visual attention among ASD children with intellectual disabilities, children with intellectual disabilities and typical development: Evidence from eye-tracking and fMRI.

Traditional picture books for children come with colourful images and a multitude of elements to attract attention and increase the reading interest of typical-developing (TD) children. However, children with Autism Spectrum Disorder (ASD) are less capable of filtering out unimportant elements in pictures and focusing on social items (e.g., human faces). This study proposed that the removal of background and less important elements in the pictures of children's storybooks could facilitate better attention and enhance children with ASD's focus on the main object and thus the intended meaning of the storybook. We adopted pictures from a well-known children's book and modified them by removing the inessential background elements. Then, ASD children with intellectual disabilities (ASD+ID) (n = 40), children with ID (n = 38) and TD (n = 40) were asked to view the original and modified pictures in an eye-tracking experiment, respectively. Additionally, brain activation of ASD+ID participants (n = 10) was recorded as they were viewing those pictures in an fMRI scan. Eye-tracking found that ASD+ID children viewed the modified pictures with significantly longer average fixations, fewer fixations, fewer saccades, and higher fixation/saccade duration ratio. Contrary to the original pictures, no significant differences were found among ASD+ID, ID only and TD. Especially, ASD+ID group showed highly similar visual patterns to the TD participants when viewing the modified pictures and particularly focusing on the main character in the pictures. Additional fMRI evidence on ASD+ID group also revealed that modified pictures were associated with enhanced activation in bilateral fusiform gyri as compared to those from original pictures, which might suggest increased visual attention. Theoretical and practical implications were discussed in light of our findings.

Sex differences in the nonlinear association of triglyceride glucose index with all-cause and cardiovascular mortality in the general population.

BACKGROUND: The evidence on the association between the triglyceride glucose (TyG) index and the risk of death in the general population remains controversial. This study aims to investigate the relationship between the TyG index and all-cause and cardiovascular mortality in the general population, with a focus on sex differences. METHODS: This prospective cohort study analyzed data from the National Health and Nutrition Examination Survey (1999-2002), comprising 7,851 US adults. The study employed multivariate Cox proportional hazards regression and two-segment Cox hazard regression models to evaluate the sex-specific differences in the relationship between the TyG index and all-cause and cardiovascular mortality. RESULTS: After 11,623 person-years of follow-up, there were 539 deaths, with 10.56% due to all-cause mortality and 2.87% due to cardiovascular mortality. After adjusting for multiple variables, our study found a U-shaped association of the TyG index with all-cause and cardiovascular mortality, with inflection points at 9.36 and 9.52. A significant sex difference was observed in the association between the TyG index and mortality. Below the inflection point, the relationship between the TyG index and mortality was consistent in males and females. However, above the inflection point, only males exhibited a positive association between the TyG index and all-cause mortality (adjusted hazard risk [HR], 1.62, 95% confidence interval [CI], 1.24-2.12) and cardiovascular mortality (adjusted HR, 2.28, 95% CI, 1.32-3.92). CONCLUSIONS: Our study showed a U-shaped association between the TyG index and all-cause and cardiovascular mortality in the general population. Furthermore, sex differences were observed in the association between the TyG index and mortality once it exceeded a certain threshold.

Clinical outcome of lesion size index-guided high-power radiofrequency catheter ablation for pulmonary vein isolation in patients with atrial fibrillation: 2-year follow-up.

INTRODUCTION: The long-term efficacy of high-power (50 W) ablation guided by lesion size index (LSI-guided HP) for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF) remains undetermined. Our study sought to assess the clinical efficacy of LSI-guided HP ablation for PVI in patients with AF and explore the potential predictors associated with clinical outcomes. METHODS: We consecutively included 186 patients with AF who underwent LSI-guided HP (50 W) ablation at Fuwai Hospital from June 2019 to October 2021. The target LSI values of 4.5-5.5 and 4.0-4.5 at the anterior and posterior walls, respectively, were used in our study. The baseline clinical characteristics, procedural and ablation data, and clinical outcomes were evaluated. The independent potential predictors associated with AF recurrence were further evaluated. RESULTS: The incidence rate of first-pass PVI was 83.9% (156/186). A total of 11 883 lesions were analyzed, and compared with posterior walls of pulmonary veins, anterior walls had significantly lower mean contact force (8.2 ± 3.0 vs. 8.3 ± 2.3 g, p = .015), longer mean radiofrequency duration (16.9 ± 7.2 vs. 12.9 ± 4.5 s, p < .001) and higher mean LSI (4.8 ± 0.2 vs. 4.4 ± 0.2, p < .001). The overall incidence of periprocedural complications was 3.7%, and steam pops without pericardial effusion occurred in three patients (1.6%). During a mean follow-up of 24.0 ± 8.4 months, the overall AF recurrence-free survival was 87.1% after a single procedure. Patients with paroxysmal AF had a higher incidence of freedom from AF recurrence than those with persistent AF (91.2% vs. 80.8%, log-rank p = .034). Higher LSI (HR 0.50, p < .001) and paroxysmal AF (HR 0.39, p = .029) were significantly associated with decreased AF recurrence. By receiver operating characteristic analysis, the LSI of 4.7 and 4.3 for the anterior and posterior walls of the PVs had the highest predictive value for AF recurrence, respectively. CONCLUSION: LSI-guided HP (50 W) ablation for PVI was an efficient and safe strategy and led to favorable single-procedure 2-year AF recurrence-free survival in patients with AF. Higher LSI and paroxysmal AF were independent predictors of decreased 2-year AF recurrence. The LSI of 4.7 for the anterior wall and 4.3 for the posterior wall of the PVs were the best cutoff values for predicting AF recurrence after LSI-guided HP ablation.

Incremental Value of Right Ventricular Outflow Tract Diameter in Risk Assessment of Chronic Heart Failure Patients with Implantable Cardioverter Defibrillators: Development of RVOTD-ICD Benefit Score in Real-World Setting.

Background: Left ventricular ejection fraction (LVEF) remains the basic reference for the prevention of sudden cardiac death (SCD) patients, while right ventricular (RV) abnormalities have now been associated with SCD risk. A modified benefit assessment tool incorporating RV function parameters in consideration of implantable cardioverter defibrillators (ICD) insertion should be taken into account. Methods: We enrolled 954 chronic heart failure (CHF) patients (age 58.8 ± 13.1 years; 79.0% male) with quantitative measurements of right ventricular outflow tract diameter (RVOTD) before ICD implantation and then divided them according to the median level of RVOTD. The predictive value of RVOTD in life-threatening ventricular tachycardia (VT)/ventricular fibrillation (VF) vs. non-arrhythmic mortality (defined as death without prior sustained VT/VF), was evaluated respectively. Based on RVOTD and other identified risk factors, a simple risk assessment tool, RVOTD-ICD benefit score, was developed. Results: A higher RVOTD level was significantly associated with an increased risk of VT/VF (per 1 standard deviation (SD) increase, hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.11-1.33; p = 0.002) but not non-arrhythmic mortality (per 1 SD increase, hazard ratio, 0.93; 95% CI, 0.66-1.33; p = 0.709) after multivariable adjustment. Three benefit groups were created based on RVOTD-ICD benefit score, which was calculated from VT/VF score (younger age, higher RVOTD, diuretic use, prior non-sustainable VT, prior sustainable VT/VF) and non-arrhythmic mortality scores (older age, renin-angiotensin-aldosterone system inhibitors use, diabetes, higher left ventricular end-diastolic diameter, New York Heart Association III/IV, higher N-terminal pro-B-type natriuretic peptide levels). In the highest RVOTD-ICD benefit group, the 3-year risk of VT/VF was nearly 8-fold higher than the corresponding risk of non-arrhythmic mortality (39.2% vs. 4.8%, p < 0.001). On the contrary, the 3-year risk of VT/VF was similar to the risk of non-arrhythmic mortality (21.9% vs. 21.3%, p = 0.405) in the lowest benefit group. RVOTD-ICD benefit score system yielded improvement in discrimination for VT/VF, non-arrhythmic mortality, and all-cause mortality than Multicenter Automatic Defibrillator Implantation Trial (MADIT)-ICD benefit score in this cohort. Conclusions: Higher RVOTD was associated with significantly increased risk of sustained VT/VF in CHF patients. A simple risk assessment tool incorporating RVOTD (RVOTD-ICD benefit score) could be generalized to ICD populations, and optimize the decision-making process of ICD implantation.

Machine Learning-Based Phenomapping in Patients with Heart Failure and Secondary Prevention Implantable Cardioverter-Defibrillator Implantation: A Proof-of-Concept Study.

Background: Previous studies have failed to implement risk stratification in patients with heart failure (HF) who are eligible for secondary implantable cardioverter-defibrillator (ICD) implantation. We aimed to evaluate whether machine learning-based phenomapping using routinely available clinical data can identify subgroups that differ in characteristics and prognoses. Methods: A total of 389 patients with chronic HF implanted with an ICD were included, and forty-four baseline variables were collected. Phenomapping was performed using hierarchical k-means clustering based on factor analysis of mixed data (FAMD). The utility of phenomapping was validated by comparing the baseline features and outcomes of the first appropriate shock and all-cause death among the phenogroups. Results: During a median follow-up of 2.7 years for device interrogation and 5.1 years for survival status, 142 (36.5%) first appropriate shocks and 113 (29.0%) all-cause deaths occurred. The first 12 principal components extracted using the FAMD, explaining 60.5% of the total variability, were left for phenomapping. Three mutually exclusive phenogroups were identified. Phenogroup 1 comprised the oldest patients with ischemic cardiomyopathy; had the highest proportion of diabetes mellitus, hypertension, and hyperlipidemia; and had the most favorable cardiac structure and function among the phenogroups. Phenogroup 2 included the youngest patients, mostly those with non-ischemic cardiomyopathy, who had intermediate heart dimensions and function, and the fewest comorbidities. Phenogroup 3 had the worst HF progression. Kaplan-Meier curves revealed significant differences in the first appropriate shock (p = 0.002) and all-cause death (p < 0.001) across the phenogroups. After adjusting for medications in Cox regression, phenogroups 2 and 3 displayed a graded increase in appropriate shock risk (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.03-2.28, p = 0.033; HR 2.21, 95% CI 1.42-3.43, p < 0.001, respectively; p for trend < 0.001) compared to phenogroup 1. Regarding mortality risk, phenogroup 3 was associated with an increased risk (HR 2.25, 95% CI 1.45-3.49, p < 0.001). In contrast, phenogroup 2 had a risk (p = 0.124) comparable with phenogroup 1. Conclusions: Machine-learning-based phenomapping can identify distinct phenotype subgroups in patients with clinically heterogeneous HF with secondary prophylactic ICD therapy. This novel strategy may aid personalized medicine for these patients.

Independent and Joint Association of Statin Therapy with Adverse Outcomes in Heart Failure Patients with Atrial Fibrillation Treated with Cardiac Resynchronization Therapy.

Background: The joint association of atrial fibrillation (AF) and statin therapy with adverse outcomes in heart failure (HF) patients with cardiac resynchronization therapy (CRT) has not been fully investigated so far. The purpose of this study was to explore the independent and joint association of AF and statin therapy with adverse outcomes. Methods: Study patients were divided into four groups according to AF status and statin use: Non-AF/Statin, Non-AF/Non-Statin, AF/Statin, and AF/Non-Statin. Multivariate Cox proportional hazards regression models were used to evaluate the independent and joint association of AF and statin therapy with poor prognosis. Results: Among 685 CRT patients, there were 180 deaths (26.5%) and 198 HF hospitalization (29.6%) during the 14 years of follow-up. AF was associated with a 46% increased risk of all-cause mortality (HR, 1.46; 95% CI, 1.03-2.07) and a 59% increased risk of HF hospitalization (HR, 1.59; 95% CI, 1.16-2.20) than those without AF. However, statin therapy failed to improve the prognosis. In the joint analysis, compared with the Non-AF/Statin group, the AF/Non-Statin group suffered a higher risk of all-cause mortality (HR, 1.75; 95% CI, 1.04-2.93) and HF hospitalization (HR, 1.76; 95% CI, 1.08-2.86). Furthermore, adding AF to the traditional risk factor model significantly improved the predictive value for death (C-statistic from 0.654 to 0.691) and HF (C-statistic from 0.613 to 0.675). Conclusion: AF was associated with poor prognosis, and statin use failed to improve the prognosis. Further analysis showed that statin therapy is ineffective in improving prognosis and fails to attenuate the adverse effects of AF.

Length of Hospitalization-Related Differences and Associated Long-Term Prognosis of Patients with Cardiac Resynchronization Therapy: A Propensity Score-Matched Cohort.

Previous studies indicated that prolonged lengths of hospitalization (LOH) during cardiac resynchronization therapy (CRT) implantation are associated with poorer physical status and higher in-hospital mortality. However, evidence on the impact of LOH on the long-term prognosis of CRT patients is limited. The purpose of this study was to assess LOH-related prognostic differences in CRT patients. In the propensity score-matched cohort, patients with standard LOH (≤7 days, n = 172) were compared with those with prolonged LOH (>7 days, n = 172) for cardiac function and study outcomes during follow-up. The study outcomes were all-cause death and heart failure (HF) hospitalization. In addition, cardiac function and changes in cardiac function at the follow-up period were used for comparison. At a mean follow-up of 3.36 years, patients with prolonged LOH, as compared with those with standard LOH, were associated with a significantly higher risk of all-cause death (hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.18−2.96, p = 0.007), and a higher risk of HF hospitalization (HR 1.68, 95% CI 1.08−2.63, p = 0.023). Moreover, patients with standard LOH had a more significant improvement in cardiac function and a pronounced reduction in QRS duration during follow-up than those with prolonged LOH. LOH-associated differences were found in the long-term prognosis of CRT patients. Patients with prolonged LOH had a worse prognosis than those with standard LOH.

Combined association of triglyceride-glucose index and systolic blood pressure with all-cause and cardiovascular mortality among the general population.

BACKGROUND: The combined association of triglyceride-glucose (TyG) index and different systolic blood pressure (SBP) levels with all-cause and cardiovascular mortality among the general population remains unclear. METHODS: In this study, 6245 individuals were from the National Health and Nutrition Examination Survey (1999-2002). The study endpoints were all-cause and cardiovascular mortality. Multivariate Cox proportional hazards regression models were used to explore the combined association of TyG index and different SBP levels with all-cause and cardiovascular mortality. RESULTS: During a mean follow-up period of 66.8 months, a total of 284 all-cause deaths (331/100000 person-years) and 61 cardiovascular deaths (66/100000 person-years) were recorded. Multivariate Cox regression analysis revealed that the combination of low TyG index and low SBP (< 120 mmHg and < 130 mmHg) was associated with a reduced risk of all-cause and cardiovascular mortality than others. However, survival benefit was not observed in the combined group with the low TyG index and SBP < 140 mmHg. Furthermore, the mortality rate in the combined group of low TyG index and low SBP gradually increased with the elevation of SBP level. CONCLUSION: The combination of low TyG index and low SBP (< 120 mmHg and < 130 mmHg) was associated with a lower risk of all-cause and cardiovascular mortality. However, no survival benefit was observed in the combined group of low TyG index and SBP < 140 mmHg.

Toward Better Risk Stratification for Implantable Cardioverter-Defibrillator Recipients: Implications of Explainable Machine Learning Models.

Background: Current guideline-based implantable cardioverter-defibrillator (ICD) implants fail to meet the demands for precision medicine. Machine learning (ML) designed for survival analysis might facilitate personalized risk stratification. We aimed to develop explainable ML models predicting mortality and the first appropriate shock and compare these to standard Cox proportional hazards (CPH) regression in ICD recipients. Methods and Results: Forty-five routine clinical variables were collected. Four fine-tuned ML approaches (elastic net Cox regression, random survival forests, survival support vector machine, and XGBoost) were applied and compared with the CPH model on the test set using Harrell's C-index. Of 887 adult patients enrolled, 199 patients died (5.0 per 100 person-years) and 265 first appropriate shocks occurred (12.4 per 100 person-years) during the follow-up. Patients were randomly split into training (75%) and test (25%) sets. Among ML models predicting death, XGBoost achieved the highest accuracy and outperformed the CPH model (C-index: 0.794 vs. 0.760, p < 0.001). For appropriate shock, survival support vector machine showed the highest accuracy, although not statistically different from the CPH model (0.621 vs. 0.611, p = 0.243). The feature contribution of ML models assessed by SHAP values at individual and overall levels was in accordance with established knowledge. Accordingly, a bi-dimensional risk matrix integrating death and shock risk was built. This risk stratification framework further classified patients with different likelihoods of benefiting from ICD implant. Conclusions: Explainable ML models offer a promising tool to identify different risk scenarios in ICD-eligible patients and aid clinical decision making. Further evaluation is needed.

Independent and joint association of N-terminal pro-B-type natriuretic peptide and left ventricular mass index with heart failure risk in elderly diabetic patients with right ventricular pacing.

Background: Elevated levels of N-terminal pro-B natriuretic peptide (NT-proBNP) and left ventricular hypertrophy (LVH) are independent risk factors for heart failure (HF). In addition, right ventricular pacing (RVP) is an effective treatment strategy for bradyarrhythmia, but long-term RVP is associated with HF. However, there is limited evidence on the independent and combined association of NT-proBNP and left ventricular mass index (LVMI) with HF risk in elderly diabetic patients with long-term RVP. Methods: Between January 2017 and January 2018, a total of 224 elderly diabetic patients with RVP at Fuwai Hospital were consecutively included in the study, with a 5-year follow-up period. The study endpoint was the first HF readmission during follow-up. This study aimed to explore the independent and joint relationship of NT-proBNP and LVMI with HF readmission in elderly diabetic patients with long-term RVP, using a multivariate Cox proportional hazards regression model. Results: A total of 224 (11.56%) elderly diabetic patients with RVP were included in the study. During the 5-year follow-up period, a total of 46 (20.54%) patients suffered HF readmission events. Multivariate Cox proportional hazards regression analysis showed that higher levels of NT-proBNP and LVMI were independent risk factors for HF readmission [NT-proBNP: hazard risk (HR) = 1.05, 95% confidence interval (CI): 1.01-1.10; LVMI: HR = 1.14, 95% CI: 1.02-1.27]. The optimal cut-off point of NT-proBNP was determined to be 330 pg/ml by receiver operating characteristic (ROC) curve analysis. Patients with NT-proBNP > 330 pg/ml and LVH had a higher risk of HF readmission compared to those with NT-proBNP ≤ 330 pg/ml and non-LVH (39.02% vs. 6.17%; HR = 7.72, 95% CI: 1.34-9.31, P < 0.001). Conclusion: In elderly diabetic patients with long-term RVP, NT-proBNP and LVMI were associated with the risk of HF readmission. Elevated NT-proBNP combined with LVH resulted in a significantly higher risk of HF readmission.

Bronchoscopic Treatment of Giant Emphysematous Bullae with Endobronchial Silicone Plugs.

Purpose: Surgical bullectomy is the standard treatment of giant emphysematous bulla (GEB). However, bronchoscopic treatment should be considered as an alternative approach for patients who are unfit for surgical treatment. The study aimed to evaluate the clinical efficacy of endobronchial occlusion for the treatment of GEB using silicone plugs. Methods: This retrospective study recruited four patients with GEB who were unsuitable for surgery. Preoperative planning was performed using high-resolution computed tomography and a virtual bronchoscopic navigation system. Customized silicone plugs were then placed in the target airway via bronchoscopy to cause GEB regression and atelectasis. Results: All procedures were completed successfully in four patients. Three months after the procedures, compared with baseline, increases in the mean forced expiratory volume in 1 s (from 1.20 L/s to 1.33 L/s), forced vital capacity (from 2.63 L to 2.90 L), diffusion lung capacity for carbon monoxide (from 29% to 41% of the predicted value) and 6-minute walking test (from 412 m to 474 m) were observed. Additionally, the mean total lung capacity (from 6.80 L to 6.35 L), residual volume (from 3.97 L to 3.52 L), and St. George's Respiratory Questionnaire scores (from 67 to 45) were all lower than baseline data. Conclusion: Our preliminary results demonstrated that the endobronchial placement of silicone plugs could be a low-cost, safe, and effective choice for the treatment of GEB in surgically unfit patients.