陈旭华
中国医学科学院阜外医院 心律失常中心
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.
Therapeutic advances in chronic disease 2024
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.
BMC medicine 2023
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.
Diabetology & metabolic syndrome 2023
Background:The prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) is well-established. However, whether it could facilitate the risk stratification of HF patients with implantable cardioverter-defibrillator (ICD) is still unclear.Objective:To determine the associations between baseline NT-proBNP and outcomes of all-cause mortality and first appropriate shock due to sustained ventricular tachycardia/ventricular fibrillation (VT/VF) in ICD recipients.Methods and results:N-terminal pro-B-type natriuretic peptide was measured before ICD implant in 500 patients (mean age 60.2 ± 12.0 years; 415 (83.0%) men; 231 (46.2%) Non-ischemic dilated cardiomyopathy (DCM); 136 (27.2%) primary prevention). The median NT-proBNP was 854.3 pg/ml (interquartile range [IQR]: 402.0 to 1,817.8 pg/ml). We categorized NT-proBNP levels into quartiles and used a restricted cubic spline to evaluate its nonlinear association with outcomes. The incidence rates of mortality and first appropriate shock were 5.6 and 9.1%, respectively. After adjusting for confounding factors, multivariable Cox regression showed a rise in NT-proBNP was associated with an increased risk of all-cause mortality. Compared with the lowest quartile, the hazard ratios (HRs) with 95% CI across increasing quartiles were 1.77 (0.71, 4.43), 3.98 (1.71, 9.25), and 5.90 (2.43, 14.30) for NT-proBNP (p for trend < 0.001). A restricted cubic spline demonstrated a similar pattern with an inflection point found at 3,231.4 pg/ml, beyond which the increase in NT-proBNP was not associated with increased mortality (p for nonlinearity < 0.001). Fine-Gray regression was used to evaluate the association between NT-proBNP and first appropriate shock accounting for the competing risk of death. In the unadjusted, partial, and fully adjusted analysis, however, no significant association could be found regardless of NT-proBNP as a categorical variable or log-transformed continuous variable (all p > 0.05). No nonlinearity was found, either (p = 0.666). Interactions between NT-proBNP and predefined factors were not found (all p > 0.1).Conclusion:In HF patients with ICD, the rise in NT-proBNP is independently associated with increased mortality until it reaches the inflection point. However, its association with the first appropriate shock was not found. Patients with higher NT-proBNP levels might derive less benefit from ICD implant.
Frontiers in cardiovascular medicine 2022
AIMS:This study aimed to develop and validate a competing risk nomogram for predicting all-cause mortality and heart transplantation (HT) before first appropriate shock in non-ischaemic dilated cardiomyopathy (DCM) patients receiving implantable cardioverter-defibrillators (ICD).METHODS AND RESULTS:A total of 218 consecutive DCM patients implanted with ICD between 2010 and 2019 at our institution were retrospectively enrolled. Cox proportional hazards model was primarily built to identify variables associated with death and HT. Then, a Fine-Gray model, accounting for the appropriate shock as a competing risk, was constructed using these selected variables along with implantation indication (primary vs. secondary). Finally, a nomogram based on the Fine-Gray model was established to predict 1-, 3-, and 5-year probabilities of all-cause mortality and HT before first appropriate shock. The area under the receiver operating characteristic (ROC) curve (AUC), Harrell's C-index, and calibration curves were used to evaluate and internally validate the performance of this model. The decision curve analysis was applied to assess its clinical utility. The 1-, 3-, and 5-year cumulative incidence of all-cause mortality and HT without former appropriate shock were 5.3% [95% confidence interval (CI) 2.9-9.9%], 16.6% (95% CI 11-25.0%), and 25.3% (95% CI 17.2-37.1%), respectively. Five variables including implantation indication, left ventricular end-diastolic diameter, N-terminal pro-brain natriuretic peptide, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and amiodarone treatment were independently associated with it (all P < 0.05) and were used for constructing the nomogram. The 1-, 3-, and 5-year AUC of the nomogram were 0.83 (95% CI 0.73-0.94, P < 0.001), 0.84 (95% CI 0.75-0.93, P < 0.001), and 0.85 (95% CI 0.77-0.94, P < 0.001), respectively. The Harrell's C-index was 0.788 (95% CI 0.697-0.877, P < 0.001; 0.762 for the optimism-corrected C-index), showing the good discriminative ability of the model. The calibration was acceptable (optimism-corrected slope 0.896). Decision curve analysis identified our model was clinically useful within the entire range of potential treatment thresholds for ICD implantation. Three risk groups stratified by scores were significantly different between cumulative incidence curves (P < 0.001). The identified high-risk group composed 17.9% of our population and did not derive long-term benefit from ICD.CONCLUSIONS:The proposed nomogram is a simple, useful risk stratification tool for selecting potential ICD recipients in DCM patients. It might facilitate the shared decision-making between patients and clinicians.
ESC heart failure 2022
AIMS:Low blood pressure (BP) has been shown to be associated with increased mortality in patients with chronic heart failure. This study was designed to evaluate the relationships between diagnosed hypertension and the risk of ventricular arrhythmia (VA) and all-cause death in chronic heart failure (CHF) patients with implantable cardioverter-defibrillators (ICD), including those with preserved left ventricular ejection fraction (HFpEF) and indication for ICD secondary prevention. We hypothesized that a stable hypertension status, along with an increasing BP level, is associated with a reduction in the risk of VA in this population, thereby limiting ICD efficacy.METHODS:We retrospectively enrolled 964 CHF patients, with hypertension diagnosis and hospitalized BP measurements obtained before ICD implantation. The primary outcome measure was defined as the composite of SCD, appropriate ICD therapy, and sustained VT. The secondary endpoint was time to death or heart transplantation (HTx). We performed multivariable Cox proportional hazard regression and entropy balancing to calculate weights to control for baseline imbalances with or without hypertension. The Fine-Gray subdistribution hazard model was used to confirm the results. The effect of random BP measurements on the primary outcome was illustrated in the Cox model with inverse probability weighting.RESULTS:The 964 patients had a mean (SD) age of 58.9 (13.1) years; 762 (79.0%) were men. During the interrogation follow-up [median 2.81 years (interquartile range: 1.32-5.27 years)], 380 patients (39.4%) reached the primary outcome. A total of 244 (45.2%) VA events in non-hypertension patients and 136 (32.1%) in hypertension patients were observed. A total of 202 (21.0%) patients died, and 31 (3.2%) patients underwent heart transplantation (incidence 5.89 per 100 person-years; 95% CI: 5.16-6.70 per 100 person-years) during a median survival follow-up of 4.5 (IQR 2.8-6.8) years. A lower cumulative incidence of VA events was observed in hypertension patients in the initial unadjusted Kaplan-Meier time-to-event analysis [hazard ratio (HR): 0.65, 95% confidence interval (CI): 0.53-0.80]. The protective effect was robust after entropy balancing (HR: 0.71, 95% CI: 0.56-0.89) and counting death as a competing risk (HR: 0.71, 95% CI: 0.51-1.00). Hypertension diagnosis did not associate with all-cause mortality in this population. Random systolic blood pressure was negatively associated with VA outcomes (p = 0.065).CONCLUSIONS:In hospitalized chronic heart failure patients with implantable cardioverter-defibrillators, the hypertension status and higher systolic blood pressure measurements are independently associated with a lower risk of combined endpoints of ventricular arrhythmia and sudden cardiac death but not with all-cause mortality. Randomized controlled trials are needed to confirm the protective effect of hypertension on ventricular arrhythmia in chronic heart failure patients.
Journal of clinical medicine 2022
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.
Journal of cardiovascular development and disease 2022
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.
Frontiers in cardiovascular medicine 2022
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.
Journal of inflammation research 2022
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.
Journal of cardiovascular development and disease 2022
