顾敏
中国医学科学院阜外医院 心律失常中心
Harvesting biomechanical energy from cardiac motion is an attractive power source for implantable bioelectronic devices. Here, we report a battery-free, transcatheter, self-powered intracardiac pacemaker based on the coupled effect of triboelectrification and electrostatic induction for the treatment of arrhythmia in large animal models. We show that the capsule-shaped device (1.75 g, 1.52 cc) can be integrated with a delivery catheter for implanting in the right ventricle of a swine through the intravenous route, which effectively converts cardiac motion energy to electricity and maintains endocardial pacing function during the three-week follow-up period. We measure in vivo open circuit voltage and short circuit current of the self-powered intracardiac pacemaker of about 6.0 V and 0.2 μA, respectively. This approach exhibits up-to-date progress in self-powered medical devices and it may overcome the inherent energy shortcomings of implantable pacemakers and other bioelectronic devices for therapy and sensing.
Nature communications 2024
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: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.
Animal models and experimental medicine 2024
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.
Journal of cardiovascular translational research 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 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 benefits of cardiac resynchronization therapy (CRT) in heart failure patients have been shown to depend on device programming, particularly atrioventricular delay (AVD) and left ventricular (LV) pacing site selection. This study compared the hemodynamic AVD optimization for commonly used biventricular (BiV) and MultiPoint Pacing(MPP, Abbott) LV vector selection strategies.METHODS:After de novo CRT-D (Abbott Quadra Assura MP) and quadripolar LV lead (Abbott Quartet) implant, acute LV pressure was measured across a range of AVDs (60-225 ms) in four pacing modes: BiV with most proximal cathode, BiV with most distal cathode, MPP using two cathodes with earliest and latest right ventricle (RV)-LV activation times, and MPP using two cathodes with maximal anatomical separation. Hemodynamic improvement was evaluated by changes in maximum LV pressure first-derivative versus RV pacing (ΔdP/dt).RESULTS:Twenty patients (64 years old, 68% male) completed the acute pacing protocol at six centers in China. Hemodynamic improvement versus RV pacing for BiV (proximal), BiV (Distal), MPP (electrical), and MPP (anatomical) was 22.1% ± 13.6%, 23.7% ± 13.4%, 24.5% ± 13.4%, and 25.1% ± 13.9%, respectively. The best MPP setting was marginally superior to the best BiV across all patients (25.8% ± 13.4% vs. 24.5% ± 13.1%, p = .040) and in the majority of patients (75.0% vs. 25.0%, p = .004). AVD programmed as little as 20 ms from optimum significantly reduced the ΔdP/dt benefit for all modes.CONCLUSIONS:The maximal hemodynamic improvement across AV delays in this population was greater with MPP than BiV. Furthermore, patient-specific AVD programming was critical in achieving the full hemodynamic response for all BiV and MPP modes.
Pacing and clinical electrophysiology : PACE 2022
BACKGROUND:The novel arrhythmogenic right ventricular cardiomyopathy (ARVC)-associated ventricular arrhythmias (VAs) risk-prediction model endorsed by Cadrin-Tourigny et al. was recently developed to estimate visual VA risk and was identified to be more effective for predicting ventricular events than the International Task Force Consensus (ITFC) criteria, and the Heart Rhythm Society (HRS) criteria. Data regarding its application in Asians are lacking.OBJECTIVES:We aimed to perform an external validation of this algorithm in the Chinese ARVC population.METHODS:The study enrolled 88 ARVC patients who received implantable cardioverter-defibrillator (ICD) from January 2005 to January 2020. The primary endpoint was appropriate ICD therapies. The novel prediction model was used to calculate a priori predicted VA risk that was compared with the observed rates.RESULTS:During a median follow-up of 3.9 years, 57 (64.8%) patients received the ICD therapy. Patients with implanted ICDs for primary prevention had non-significantly lower rates of ICD therapy than secondary prevention (5-year event rate: 0.46 (0.13-0.66) and 0.80 (0.64-0.89); log-rank p = 0.098). The validation study revealed the C-statistic of 0.833 (95% confidence interval (CI) 0.615-1.000), and the predicted and the observed patterns were similar in primary prevention patients (mean predicted-observed risk: -0.07 (95% CI -0.21, 0.09)). However, in secondary prevention patients, the C-statistic was 0.640 (95% CI 0.510-0.770) and the predicted risk was significantly underestimated (mean predicted-observed risk: -0.32 (95% CI -0.39, -0.24)). The recalibration analysis showed that the performance of the prediction model in secondary prevention patients was improved, with the mean predicted-observed risk of -0.04 (95% CI -0.10, 0.03).CONCLUSIONS:The novel risk-prediction model had a good fitness to predict arrhythmic risk in Asian ARVC patients for primary prevention, and for secondary prevention patients after recalibration of the baseline risk.
Journal of clinical medicine 2022
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
