刘曦
中国医学科学院阜外医院 心血管内科
BACKGROUND AND OBJECTIVE:Left bundle branch pacing (LBBP) has shown the benefits in the treatment of dyssynchronous heart failure (HF). The purpose of this study was to develop a novel approach for LBBP and left bundle branch block (LBBB) in a canine model.METHODS:A "triangle-center" method by tricuspid valve annulus angiography for LBBP implantation was performed in 6 canines. A catheter was then applied for retrograde His potential recording and left bundle branch (LBB) ablation simultaneously. The conduction system was stained to verify the "triangle-center" method for LBBP and assess the locations of the LBB ablation site in relation to the left septal fascicle (LSF).RESULTS:The mean LBB potential to ventricular interval and stimulus-peak left ventricular activation time were 11.8 ± 1.2 and 35.7 ± 3.1 ms, respectively. The average intrinsic QRS duration was 44.7 ± 4.7 ms. LBB ablation significantly prolonged the QRS duration (106.3 ± 8.3 ms, p < .001) while LBBP significantly shortened the LBBB-QRS duration to 62.5 ± 5.3 ms (p < .001). After 6 weeks of follow-up, both paced QRS duration (63.0 ± 5.4 ms; p = .203) and LBBB-QRS duration (107.3 ± 7.4 ms; p = .144) were unchanged when comparing to the acute phase, respectively. Anatomical analysis of 6 canine hearts showed that the LBBP lead-tip was all placed in LSF area.CONCLUSION:The new approach for LBBP and LBBB canine model was stable and feasible to simulate the clinical dyssynchrony and resynchronization. It provided a useful tool to investigate the basic mechanisms of underlying physiological pacing benefits.
Journal of cardiovascular electrophysiology 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
PURPOSE:We aimed to evaluate the electrical characteristics and pacing parameters at different locations of His-Purkinje system pacing.METHODS:Patients who successfully underwent His-Purkinje system pacing with bradycardia indications from April 2018 to August 2019 were retrospectively analyzed according to the lead location confirmed by visualization of the tricuspid value annulus, postoperative echocardiography, and pacing electrocardiogram. The electrical characteristics and pacing parameters were compared among these patients.RESULTS:A total of 135 patients were retrospectively analyzed. Among them, 30 patients received atrial side HBP (aHBP group), 52 received ventricular side HBP (vHBP group), and 53 received left bundle branch pacing (LBBP group). The proportion of non-selective pacing was significantly lower in aHBP group (30.0%) than in vHBP (75.0%) and LBBP group (90.6%). LBBP had significantly shorter procedural and fluoroscopic duration than aHBP and vHBP. The capture threshold was significantly higher (1.07 ± 0.26 V/1.0 ms vs. 0.89 ± 0.22 V/1.0 ms vs. 0.77 ± 0.18 V/0.4 ms, P < 0.01, respectively), and the R-wave amplitude was significantly lower (3.71 ± 1.72 mV vs. 5.81 ± 2.37 mV vs. 10.27 ± 4.71 mV, P < 0.05 respectively) in aHBP group than those in the other two groups at implantation and during 3-month follow-up. No significant differences were observed in complications among groups during 3-month follow-up.CONCLUSION:VHBP and LBBP had better pacing performances than aHBP and might be more ideal pacing methods for bradycardia patients.
Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing 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: Left ventricular ejection fraction (LVEF) is a suboptimal indicator of risk stratification for patients with an implantable cardioverter defibrillator (ICD). Studies have shown that left ventricular end-diastolic diameter (LVEDD) was associated with all-cause mortality and ventricular arrhythmias. We examined the quantified prognostic value of LVEF and LVEDD for clinical outcomes, respectively. Method: This study retrospectively enrolled patients with ICD implantation in a single center. The associations between LVEF or LVEDD and all-cause mortality and appropriate shocks were analyzed using Cox regression and Fine-gray competing risk regression, respectively. Result: During a median follow up of 59.6 months, 168/630 (26.7%) patients died. LVEF and LVEDD were strongly associated with all-cause mortality (LVEF per 10%: HR 0.77, 95%CI 0.64−0.93, p = 0.006; LVEDD per 10 mm: HR 1.54, 95%CI 1.27−1.85, p < 0.001). After a median interrogation time of 37.1 months, 156 (24.8%) patients received at least one shock. LVEF was not associated with appropriate shock, whereas larger LVEDD (per 10 mm) was significantly associated with a higher risk of shock (HR: 1.27, 95%CI 1.06−1.52, p = 0.008). The addition of LVEF or LVEDD to clinical factors provided incremental prognostic value and discrimination improvement for all-cause mortality, while only the addition of LVEDD to clinical factors improved prognostic value for shock intervention. Conclusions: Baseline LVEF and LVEDD show a linear relationship with all-cause mortality in patients with ICD. However, whereas LVEF is not associated with shock, a linear relationship exists between LVEDD and appropriate shock. LVEDD adds more predictive value in relation to all-cause mortality and appropriate shocks than LVEF.
Journal of cardiovascular development and disease 2022
Background:Ventricular arrhythmias in patients with hypertrophic cardiomyopathy (HCM) may lead to sudden cardiac death (SCD). We aimed to investigate the relationship between electrocardiogram (ECG) indicators and the risk of appropriate implantable cardioverter-defibrillator (ICD) therapy in HCM.Methods:The HCM patients receiving ICD implantation were enrolled consecutively. QT interval correction (QTc) was calculated using Bazett's formula. Long or deep S wave in V4 lead was defined as duration time >50 ms and/or voltage amplitude >0.6 mV. The endpoint in our study was at least one ICD appropriate therapy triggered by ventricular tachyarrhythmia (VT) or ventricular fibrillation (VF), including anti-tachyarrhythmia pacing (ATP) and electrical shock.Results:A total of 149 patients with HCM (mean age 53 ± 14 years, male 69.8%) were studied. Appropriate ICD therapies occurred in 47 patients (31.5%) during a median follow-up of 2.9 years. Cox regression analysis showed that long or deep S wave in V4 lead [hazard ratio (HR) 1.955, 95% confidence interval (CI) 1.017-3.759, P = 0.045] and QTc interval (HR 1.014, 95% CI 1.008-1.021, P < 0.001) were independent risk factors for appropriate ICD therapy. The ROC showed that the optimal cut-off point value for the QTc interval to predict the appropriate ICD therapy was 464 ms, and the AUC was 0.658 (95% CI 0.544-0.762, P = 0.002). The AUC for S wave anomalies in V4 lead was 0.608 (95% CI 0.511-0.706, P = 0.034). We developed a new model that combined the QTc interval and S wave anomalies in V4 lead based on four patient groups. Patients with QTc ≥464 ms and long or deep V4-S wave had the highest risk of developing appropriate ICD therapy (log-rank P < 0.0001). After adding QTc interval and V4-S wave anomalies into the HCM-risk-SCD model, the prediction effect of the new model was significantly improved, and the NRI was 0.302.Conclusions:In this HCM cohort, QTc and S wave anomalies in V4 lead were found to be significant and strong predictors of the risk of appropriate ICD therapy. Patients with QTc ≥464 ms and long or deep S wave had the highest risk. After QTc interval and V4-S wave anomalies adding to the HCM-risk-SCD model, the prediction effect is significantly improved.
Frontiers in cardiovascular medicine 2022
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.
Cardiovascular drugs and therapy 2022
