Performance of Subcutaneous Implantable Cardioverter Defibrillator (S-ICD) in Chinese Population with Primary Prevention Indications: A Prospective Observational Cohort Study.

BACKGROUND International studies have shown that use of a subcutaneous implantable cardioverter defibrillator (S-ICD) could reduce lead-related complications while maintaining adequate defibrillation performance; however, data from the Chinese population or other Asian groups are limited. MATERIAL AND METHODS SCOPE is a prospective, multicenter, observational cohort study. Two hundred patients with primary prevention indication for sudden cardiac death (SCD), who are candidates for S-ICD, will be enrolled. From the same population, another 200 patients who are candidates for transvenous implantable cardioverter defibrillator (TV-ICD) will be enrolled after being matched for age, sex, SCD high-risk etiology (ischemic cardiomyopathy, and non-ischemic cardiomyopathy, ion channel disease, and other) and atrial fibrillation in a 1: 1 ratio with enrolled S-ICD patients. All the patients will be followed for 18 months under standard of care. RESULTS The primary endpoint is proportion of patients free from inappropriate shock (IAS) at 18 months in the S-ICD group. The lower 95% confidence bound of the proportion will be compared with a performance goal of 90.3%, which was derived from the previous meta-analysis. The comparisons between S-ICD and TV-ICD on IAS, appropriate shock, and complications will be used as secondary endpoints without formal assumptions. CONCLUSIONS This is the first prospective multicenter study focusing on the long-term performance of S-ICD in a Chinese population. By comparing with the data derived from international historical studies and a matched TV-ICD group, data from SCOPE will allow for the assessment of S-ICD in the Chinese population in a contemporary real-world implantation level and programming techniques, which will help us to further modify the device implantation and programming protocol in this specific population in the future.

Myeloid-specific deletion of Capns1 attenuates myocardial infarction injury via restoring mitochondrial function and inhibiting inflammasome activation.

BACKGROUND: Mitochondrial dysfunction of macrophage-mediated inflammatory response plays a key pathophysiological process in myocardial infarction (MI). Calpains are a well-known family of calcium-dependent cysteine proteases that regulate a variety of processes, including cell adhesion, proliferation, and migration, as well as mitochondrial function and inflammation. CAPNS1, the common regulatory subunit of calpain-1 and 2, is essential for the stabilization and activity of the catalytic subunit. Emerging studies suggest that calpains may serve as key mediators in mitochondria and NLRP3 inflammasome. This study investigated the role of myeloid cell calpains in MI. METHODS: MI models were constructed using myeloid-specific Capns1 knockout mice. Cardiac function, cardiac fibrosis, and inflammatory infiltration were investigated. In vitro, bone marrow-derived macrophages (BMDMs) were isolated from mice. Mitochondrial function and NLRP3 activation were assessed in BMDMs under LPS stimulation. ATP5A1 knockdown and Capns1 knock-out mice were subjected to MI to investigate their roles in MI injury. RESULTS: Ablation of calpain activities by Capns1 deletion improved the cardiac function, reduced infarct size, and alleviated cardiac fibrosis in mice subjected to MI. Mechanistically, Capns1 knockout reduced the cleavage of ATP5A1 and restored the mitochondria function thus inhibiting the inflammasome activation. ATP5A1 knockdown antagonized the protective effect of Capns1 mKO and aggravated MI injury. CONCLUSION: This study demonstrated that Capns1 depletion in macrophages mitigates MI injury via maintaining mitochondrial homeostasis and inactivating the NLRP3 inflammasome signaling pathway. This study may offer novel insights into MI injury treatment.

Trimetazidine Affects Mitochondrial Calcium Uniporter Expression to Restore Ischemic Heart Function via Reactive Oxygen Species/NFκB Pathway Inhibition.

ABSTRACT: Studies have demonstrated the roles of trimetazidine beyond being an antianginal agent in ischemic heart disease (IHD) treatment associated with mechanisms of calcium regulation. Our recent studies revealed that mitochondrial calcium uniporter (MCU, the pore-forming unit responsible for mitochondrial calcium entrance) inhibition provided cardioprotective effects for failing hearts. Because trimetazidine and MCU are associated with calcium homeostasis, we hypothesized that trimetazidine may affect MCU to restore the failing heart function. In the present study, we tested this hypothesis in the context of cardiac ischemia in vivo and in vitro. The IHD model was established in male C57BL/6 mice followed by trimetazidine administration intraperitoneally at 20 mg/kg q.o.d for 8 weeks. In vitro studies were performed in a hypoxia model using primary rat neonate cardiomyocytes. The mice survival outcomes and heart function, pathohistologic, and biological changes were analyzed. The results demonstrated that trimetazidine treatment resulted in longer life spans and heart function improvement accompanied by restoration of mitochondrial calcium levels and increase in ATP production via MCU down-regulation. Studies in vitro further showed that trimetazidine treatment and MCU inhibition decreased reactive oxygen species (ROS) production, inhibited the NFκB pathway, and protected the cardiomyocytes from hypoxic injury, and vice versa. Thus, the present study unveils a unique mechanism in which trimetazidine is involved in ameliorating the ischemic failing heart via MCU down-regulation and the following mitochondrial calcium homeostasis restoration, ROS reduction, and cardiomyocyte protection through NFκB pathway inhibition. This mechanism provides a novel explanation for the treatment effects of trimetazidine on IHD.

Real-world evidence for the use of subcutaneous implantable cardioverter-defibrillators in China: A single-center experience.

BACKGROUND: Subcutaneous implantable cardioverter-defibrillators (S-ICDs) have been shown to be non-inferior to transvenous ICDs in the prevention of sudden cardiac death (SCD), but there is still a lack of evidence from clinical trials in China. We investigated whether S­ICD implantation in the Chinese population is safe and feasible and should be promoted in the future. METHODS: Consecutive patients undergoing S­ICD implantation at our center were enrolled in this retrospective study. Data were collected within the median follow-up period of 554 days. Data concerning patient selection, implantation procedures, complications, and episodes of shock were analyzed. RESULTS: In total, 70.2% of all 47 patients (median age = 39 years) were included for secondary prevention of SCD with different etiologies. Vector screening showed that 98% of patients were with > 1 appropriate vector in all postures. An intraoperative defibrillation test was not performed on six patients because of the high risk of disease deterioration, while all episodes of ventricular fibrillation induced post implantation were terminated by one shock. As expected, no severe complications (e.g., infection and device-related complications) were observed, except for one case of delayed healing of the incision. Overall, 15 patients (31.9%) experienced appropriate shocks (AS) with all episodes terminated by one shock. Two patients (4.3%) experienced inappropriate shocks (IAS) due to noise oversensing, resulting in a high Kaplan-Meier IAS-free rate of 95.7%. CONCLUSION: Based on appropriate patient selection and standardized implantation procedures, this real-world study confirmed the safety and efficacy of S­ICD in Chinese patients, indicating that it may help to promote the prevention of SCD in China.

Cardiac resynchronization therapy via left bundle branch pacing vs. optimized biventricular pacing with adaptive algorithm in heart failure with left bundle branch block: a prospective, multi-centre, observational study.

AIMS: The purpose of our study was to evaluate the feasibility and efficacy of cardiac resynchronization therapy (CRT) via left bundle branch pacing (LBBP-CRT) compared with optimized biventricular pacing (BVP) with adaptive algorithm (BVP-aCRT) in heart failure with reduced left ventricular ejection fraction ≤35% (HFrEF) and left bundle branch block (LBBB). METHODS AND RESULTS: One hundred patients with HFrEF and LBBB undergoing CRT were prospectively enrolled in a non-randomized fashion and divided into two groups (LBBP-CRT, n = 49; BVP-aCRT, n = 51) in four centres. Implant characteristics and echocardiographic parameters were accessed at baseline and during 6-month and 1-year follow-up. The success rate for LBBP-CRT and BVP-aCRT was 98.00% and 91.07%. Fused LBBP had the greatest reduced QRS duration compared to BVP-aCRT (126.54 ± 11.67 vs. 102.61 ± 9.66 ms, P < 0.001). Higher absolute left ventricular ejection fraction (LVEF) and △LVEF was also achieved in LBBP-CRT than BVP-aCRT at 6-month (47.58 ± 12.02% vs. 41.24 ± 10.56%, P = 0.008; 18.52 ± 13.19% vs. 12.89 ± 9.73%, P = 0.020) and 1-year follow-up (49.10 ± 10.43% vs. 43.62 ± 11.33%, P = 0.021; 20.90 ± 11.80% vs. 15.20 ± 9.98%, P = 0.015, P = 0.015). There was no significant difference in response rate between two groups while higher super-response rate was observed in LBBP-CRT as compared to BVP-aCRT at 6 months (53.06% vs. 36.59%, P = 0.016) and 12 months (61.22% vs. 39.22%, P = 0.028) during follow-up. The pacing threshold was lower in LBBP-CRT at implant and during 1-year follow-up (both P < 0.001). Procedure-related complications and adverse clinical outcomes including heart failure hospitalization and mortality were not significantly different in two groups. CONCLUSIONS: The feasibility and efficacy of LBBP-CRT demonstrated better electromechanical resynchronization and higher clinical and echocardiographic response, especially higher super-response than BVP-aCRT in HFrEF with LBBB.

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

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

Acute hemodynamic impact of atrioventricular delay and left ventricular pacing vector programming in MultiPoint Pacing.

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.

Implantable device measured objective daily physical activity as a predictor of long-term all-cause mortality and cardiac death in patients with age > 75 years and high risk of sudden cardiac death: a cohort study : Physical activity and patients over 75 years old.

BACKGROUND: To study the relationship between objective daily physical activity (PA), as measured by implantable cardioverter defibrillators (ICDs)/cardiac resynchronization therapy defibrillators (CRTDs), and long-term prognoses in patients with age > 75 years at high risk of sudden cardiac death (SCD). METHODS: In total, 133 patients with age > 75 years old (age 79.52 ± 3.68 years) in the SUMMIT study were retrospectively analysed. The major endpoint was all-cause mortality, and the minor endpoint was cardiac death. RESULTS: The mean follow-up time was 57.1 ± 24.2 months (range: from 4 to 96 months). In total, 46 all-cause mortality and 23 cardiac death events occurred. The receiver operating characteristic curve indicated a baseline PA cut-off value of 6.47% (93 min/day) can predict all-cause mortality in patients with age > 75 years, with an area under the curve of 0.670 (95% confidence interval (CI): 0.573-0.767, P = 0.001). The sensitivity was 67.4%, and the specificity was 66.7%. Patients with baseline PA ≤ 6.47% had higher rates of all-cause mortality (51.7% vs 20.5%, P < 0.001) and cardiac death (25.0% vs 11.0%, P = 0.040). The estimated Kaplan-Meier survival curves showed that patients with PA ≤ 6.47% had an increased cumulative incidence of all-cause mortality (Log-rank P < 0.0001) and cardiac death (Log-rank P = 0.0067). Multivariate Cox regression analysis showed that PA ≤ 6.47% was an independent predictor of all-cause mortality (hazard ratio (HR) 3.137, 95% CI: 1.667-5.904, P < 0.001) and cardiac death (HR value 3.345, 95% CI: 1.394-8.028, P = 0.007). CONCLUSIONS: Daily PA of about 1.5 h was associated with lower all-cause mortality and cardiac death risk in patients with age > 75 years and high risk of SCD with ICDs/CRTDs. PA monitoring may aid in long-term management of older patients at high risk of SCD.

Association between cardiac autonomic function and physical activity in patients at high risk of sudden cardiac death: a cohort study.

BACKGROUND: High levels of physical activity (PA) and heart rate variability (HRV) are associated with cardiovascular benefits in patients with cardiovascular diseases. HRV, representing cardiac autonomic function, is positively associated with PA. However, the impacts of PA and cardiac autonomic function on cardiovascular outcomes were not analysed in the same study population. This lack of evidence supported our hypothesis that PA might contribute to cardiovascular benefits via enhanced cardiac autonomic function. METHODS: Patients with implantable cardioverter defibrillator (ICD) or cardiac resynchronisation therapy defibrillator (CRT-D) implantation were included from the SUMMIT registry. HRV and PA values were assessed during the first 30-60 days post device implantation using a continuous home monitoring system. Causal mediation analysis was conducted to explore the possible mediation function of HRV in the association of PA with long-term cardiac death and all-cause mortality in patients at a high risk of sudden cardiac death. RESULTS: Over a mean follow-up period of 47.7 months, 63 cardiac deaths (18.9%) and 85 all-cause death events (25.5%) were observed among 342 patients with ICD/CRT-D implantation. A positive linear association between HRV and PA was demonstrated and the ß value of HRV was 0.842 (95% confidence interval [CI]: 0.261-1.425, P = 0.005) in the multiple linear regression analysis. Multivariable Cox proportional hazards analysis revealed that high levels of PA (≥11.0%) and HRV (≥75.9 ms) were independent protective factors against cardiac death (PA: hazard ratio [HR] = 0.273; 95% CI, 0.142-0.526, P < 0.001; HRV: HR = 0.224; 95% CI, 0.103-0.489, P < 0.001) and all-cause mortality (PA: HR = 0.299; 95% CI, 0.177-0.505, P < 0.001; HRV: HR = 0.394; 95% CI, 0.231-0.674, P = 0.001). Causal mediation analysis demonstrated partial mediation effects of PA that were mediated through HRV on cardiac death (mediation proportion = 12.9, 95%CI: 2.2-32.0%, P = 0.006) and all-cause mortality (mediation proportion = 8.2, 95%CI: 1.6-20.0%, P = 0.006). CONCLUSIONS: HRV might be a modest mediator in the association between high levels of PA and the reduced risks of cardiac death and all-cause mortality in ICD/CRT-D recipients. This finding supports that enhanced cardiac autonomic function might be one of the underlying mechanisms by which regular PA contributes to cardiovascular benefits.

A new method to recommend left ventricular lead positions for improved CRT volumetric response and long-term prognosis.

OBJECTIVES: Using ECG-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), we sought to develop and validate a new method to recommend left ventricular (LV) lead positions in order to improve volumetric response and long-term prognosis after cardiac resynchronization therapy (CRT). METHODS: Seventy-nine patients received gated SPECT MPI at baseline, and echocardiography at baseline and follow-up. The volumetric response referred to a reduction of ≥ 15% in LV end-systolic volume 6 months after CRT. After excluding apical, septal, and scarred segments, there were three levels of recommended segments: (1) the optimal recommendation: the latest contracting viable segment; (2) the 2nd recommendation: the late contracting viable segments whose contraction delays were within 10° of the optimal recommendation; and (3) the 3rd recommendation: the viable segments adjacent to the optimal recommendation when there was no late contracting viable segment. RESULTS: After excluding 11 patients whose LV lead was placed in apical or scarred segments, 75.6% of the patients concordant to recommended LV segments (n = 41) responded to CRT while 51.9% of those with non-recommended LV lead locations (n = 27) were responders (P = .043). Response rates were 76.9%, 76.9% , and 73.3% (P = .967), respectively, when LV lead was implanted in the optimal recommendation (n = 13), the 2nd recommendation (n = 13), and the 3rd recommendation (n = 15). LV leads placed at recommended segments reduced composite events of all-cause mortality or heart failure (HF) rehospitalization compared with pacing at non-recommended segments (log-rank χ2 = 5.623, P = .018). CONCLUSIONS: Pacing in the recommended LV lead segments identified on gated SPECT MPI was associated with improved volumetric response to CRT and long-term prognosis.

Pericardial effusion caused by accidently placing a Micra transcatheter pacing system into the coronary sinus.

BACKGROUND: Leadless pacemaker has been acknowledged as a promising pacing strategy to prevent pocket and lead-related complications. Although rare, cardiac perforation remains a major safety concern for implantation of Micra transcatheter pacing system (TPS). CASE PRESENTATION: A 83-year-old female with low body mass index (18.9 kg m-2) on dual anti-platelet therapy, was indicated for Micra TPS implantation due to sinus arrest and paroxysmal atrial flutter. The patient developed mild pericardial effusion during the procedure since the delivery catheter was accidentally placed into the coronary sinus for several times. Cardiac perforation with moderate pericardial effusion and pericardial tamponade was detected 2 h post-procedure. The patient was treated with immediately pericardiocentesis and recovered without further invasive therapy. CONCLUSION: Pericardial effusion caused by accidently placing a delivery catheter into the coronary sinus is rare but should be carefully considered in Micra TPS implantation, especially for those with periprocedural anti-platelet therapy.

The risk factors of new-onset atrial fibrillation after pacemaker implantation.

OBJECTIVE: The aim of this study was to determine the incidence of newly detected atrial fibrillation (AF) in patients following dual-chamber pacemaker (PPM) implantation and to define the clinical predictors of new-onset AF in a Chinese cohort. METHODS: A total of 219 patients without documented AF that underwent dual-chamber PPM implantation for sick sinus syndrome (SSS) (n = 88) or atrioventricular block (AVB) (n = 131) were prospectively studied. All patients were invited to follow-up at 1 month, 3 months and 6 months after the pacemaker implantation procedure, and once every 6 months thereafter. An atrial high-rate episode (AHRE) ≥5 min and an atrial rate ≥180 bpm was defined as AF. RESULTS: During follow-up of 884 ± 180 days, AF was detected in 56 (26%) patients. Using Kaplan-Meier survival curves with Log-rank test, SSS patients with a cumulative percentage of ventricular pacing (Cum % VP) ≥60% had a significantly higher rate of new-onset AF compared to AVB patients (p = 0.026) and SSS patients with Cum % VP <60% (p = 0.018). On multivariate Cox regression analysis, higher Cum % VP independently predicted higher morbidity of newly detected AF (hazard ratio [HR] 1.01; confidence interval [CI] 1.00 ~ 1.02; p = 0.035) among SSS patients. Larger left atrial (LA) dimension was a predictor of newly detected AF (HR 1.06; CI 1.01 ~ 1.14; p = 0.046) in AVB patients. CONCLUSION: The incidence of AF following dual-chamber PPM implantation was relatively high in this Chinese cohort. High Cum % VP and larger LA dimension could independently predict new-onset AF after dual-chamber PPM implantation in SSS and AVB patients, respectively.

Angiotensin II Increases HMGB1 Expression in the Myocardium Through AT1 and AT2 Receptors When Under Pressure Overload.

High-mobility group box 1 (HMGB1) is increased in the myocardium under pressure overload (PO) and is involved in PO-induced cardiac remodeling. The mechanisms of the upregulation of cardiac HMGB1 expression have not been fully elucidated. In the present study, a mouse transverse aortic constriction (TAC) model was used, and an angiotensin II (Ang II) type 1 (AT1) receptor inhibitor (losartan) or Ang II type 2 (AT2) receptor inhibitor (PD123319) was administrated to mice for 14 days. Cardiac myocytes were cultured and treated with Ang II for 5 minutes to 48 hours conditionally with the blockage of the AT1 or AT2 receptor. TAC-induced cardiac hypertrophy was observed at 14 days after the operation, which was partially reversed by losartan, but not by PD123319. Similarly, the upregulated HMGB1 expression levels observed in both the serum and myocardium induced by TAC were reduced by losartan. Elevated cardiac HMGB1 protein levels, but not mRNA or serum levels, were significantly decreased by PD123319. Furthermore, HMGB1 expression levels in culture media and cardiac myocytes were increased following Ang II treatment in vitro, positively associated with the duration of treatment. Similarly, Ang II-induced upregulation of HMGB1 in vitro was inhibited by both losartan and PD123319. These results suggest that upregulation of HMGB1 in serum and myocardium under PO, which are partially derived from cardiac myocytes, may be induced by Ang II via the AT1 and AT2 receptors. Additionally, amelioration of PO-induced cardiac hypertrophy following losartan treatment may be associated with the reduction of HMGB1 expression through the AT1 receptor.

Patient-tailored SyncAV algorithm: A novel strategy to improve synchrony and acute hemodynamic response in heart failure patients treated by cardiac resynchronization therapy.

INTRODUCTION: Several automatic algorithms have developed to optimize the timing cycle setting in cardiac resynchronization therapy (CRT). The present study aims to investigate whether the novel device-based SyncAV algorithm could elicit better synchrony and acute hemodynamic response. METHODS AND RESULTS: Thirty five patients undergoing CRT implantation were prospectively studied. The device was programmed to three biventricular (BiV) pacing modes sequentially after the procedure: QuickOpt algorithm (mode I), SyncAV algorithm with default 50 ms offset (mode II), and SyncAV algorithm with optimized offset minimizing QRS duration (QRSd) (mode III). After each setting, electrocardiographic and echocardiographic data were collected. As a result, QRSd was reduced from 172.8 ± 17.9 ms during intrinsic conduction to 153.1 ± 15.9 ms in mode I, further narrowed to 140.5 ± 16.7 ms in mode II, and reached shortest (134.8 ± 16.1 ms) in mode III (P < .01 for all). Besides, significantly shorter QT intervals were observed in mode I (453.2 ± 45.5 ms), mode II (443.9 ± 34.2 ms) and mode III (444.1 ± 28.7 ms), compared with native condition (472.5 ± 51.2 ms) (P < .01). All three BiV modes exhibited comparable Tp Te interval and Tp Te /QT ratio (P > .05). Mode I presented significantly higher aortic velocity time integral than intrinsic conduction (21.0 ± 6.4 cm vs 18.4 ± 5.5 cm; P < .01), which was even higher in mode II (22.0 ± 6.5 cm) and mode III (23.7 ± 6.5 cm). All three BiV modes significantly reduced standard deviation of time to peak contraction of 12-LV segments (Ts-SD) (Mode I: 55.2 ± 16.5 ms, Mode II: 50.2 ± 14.7 ms, Mode III: 45.4 ± 14.4 ms) compared with intrinsic conduction (66.3 ± 18.4 ms) (P < .01), with Mode III demonstrating the smallest (P < .01). CONCLUSION: SyncAV CRT ameliorated electrical and mechanical synchrony as well as acute hemodynamic response beyond conventional QuickOpt optimization. An additional individualized adjustment to the SyncAV offset added to its advantage.

Left bundle branch area pacing is superior to right ventricular septum pacing concerning depolarization-repolarization reserve.

INTRODUCTION: Left bundle branch area pacing (LBBAP) has recently been reported to be a new physiological pacing strategy with clinical feasibility and safety. The present study aims to investigate depolarization-repolarization measures including QT interval, QT dispersion (QTD), and Tpeak-end interval (Tp Te ) in this novel LBBAP strategy. METHODS AND RESULTS: A total of 131 pacing-indicated patients were prospectively enrolled and randomized to the LBBAP group (n = 66) and right ventricular septum pacing (RVSP) group (n = 65). LBBAP was successfully achieved in 61 subjects with stable lead performance and comparable complications (ie, pocket hematoma, lead perforation, and dislodgement) compared with RVSP. Of the 61 patients with successful LBBAP, the mean LV peak activation time was 67.89 ± 6.80 ms, with the LBB potential mapped in 46 cases (75.4%). Electrocardiogram (ECG) indices were compared between these two groups before and after implantation. As a result, LBBAP yielded a narrower paced QRS duration (121.49 ± 9.87 ms vs 145.62 ± 8.89 ms; P < .001), shorter QT interval (434.16 ± 32.70 ms vs 462.66 ± 32.04 ms; P < .001), and QTc interval (472.44 ± 33.30 ms vs 499.65 ± 31.35 ms; P < .001), lower QTD (40.10 ± 8.68 ms vs 46.11 ± 10.85 ms; P = .001), and QTc D (43.57 ± 8.78 ms vs 49.86 ± 11.98 ms; P = .001), and shorter Tp Te (96.59 ± 10.76 ms vs 103.77 ± 10.16 ms; P < .001) than RVSP. However, Tp Te /QT ratio did not differ between these two groups (0.223 ± 0.026 vs 0.225 ± 0.022; P = .733). Furthermore, LBBAP displayed less increased QRS duration, QTc interval, QTD, QTc D, and a more shortened QT interval compared with RVSP (all P < .05). CONCLUSION: LBBAP proves to be a feasible and safe pacing procedure with better depolarization-repolarization reserve, which may predict lower risk of ventricular arrhythmia and sudden cardiac death.

Electrophysiological parameters and anatomical evaluation of left bundle branch pacing in an in vivo canine model.

INTRODUCTION: Left bundle branch pacing (LBBP), a form of conduction system pacing in addition to His bundle pacing (HBP), can potentially maintain left ventricular electrical synchrony with better sensing and a low and stable capture threshold. METHODS: We performed both HBP and LBBP using a canine model (n = 3; male; weight 30-40 kg). The electrocardiogram (ECG), intracardiac electrogram characteristics, and pacing parameters were compared between HBP and LBBP. The hearts were isolated and stained by Lugol's iodine (5%) to assess the relative locations of the leads in relation to the conduction system. RESULTS: The average potential to ventricle interval was longer with HBP compared to LBBP (26.67 ± 3.06 ms vs 12.67 ± 1.15 ms; P = .002). There were also notable differences in the pacing parameters between HBP and LBBP: R-wave amplitude (2.67 ± 0.42 mV vs 11.33 ± 3.06 mV; P = .008), pacing impedance (423.3 ± 40.4 vs 660.0 ± 45.8; P = .003), and threshold (2.30 ± 0.66 V/0.4ms vs 0.67 ± 0.15 V/0.4 ms; P = .014). The paced morphology of ECG was similar to the intrinsic with HBP while a right bundle branch block pattern was noted with LBBP. The anatomical evaluation revealed the location of the leads and the average lead depth was significantly more with LBBP as compared to HBP (12.33 ± 1.53 mm vs1.83 ± 0.29 mm; P < .0001). Furthermore, with LBBP, the tip of the lead helix was noted to be around the LBB. CONCLUSION: This in vivo canine model study confirms the significant differences between HBP and LBBP. Furthermore, this model provides a precise anatomic evaluation of the location and the depth of the leads in relation to the conduction system.

Dose-response association of implantable device-measured physical activity with long-term cardiac death and all-cause mortality in patients at high risk of sudden cardiac death: a cohort study.

BACKGROUND: Cardiovascular implantable electronic devices (CIEDs) with physical activity (PA) recording function can continuously and automatically collect patients' long-term PA data. The dose-response association of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy defibrillator (CRTD)-measured PA with cardiovascular outcomes in patients at high risk of sudden cardiac death (SCD) was investigated. METHODS: In total, 822 patients fulfilling the inclusion criteria were included and divided into three groups according to baseline PA tertiles: tertile 1 (< 8.04%, n = 274), tertile 2 (8.04-13.24%, n = 274), and tertile 3 (> 13.24%, n = 274). The primary endpoint was cardiac death, the secondary endpoint was all-cause mortality. RESULTS: During a mean follow-up of 59.7 ± 22.4 months, cardiac death (18.6% vs 8.8% vs 5.5%, tertiles 1-3, P < 0.001) and all-cause mortality (39.4% vs 20.4% vs 9.9%, tertiles 1-3, P < 0.001) events decreased according to PA tertiles. Compared with patients younger than 60 years old, older patients had a lower average PA level (9.6% vs 12.8%, P < 0.001) but higher rates of cardiac death (13.2% vs 8.1%, P = 0.024) and all-cause mortality (28.4% vs 16.7%, P < 0.001) events. Adjusted multivariate Cox regression analyses showed that a higher tertile of PA was associated with a lower risk of cardiac death (hazard ratio (HR) 0.41, 95% confidence interval (CI): 0.25-0.68, tertile 2 vs tertile 1; HR 0.28, 95% CI: 0.15-0.51, tertile 3 vs tertile 1, P trend < 0.001). Similar results were observed for all-cause mortality. The dose-response curve showed an inverse non-linear pattern, and a significant reduction in endpoint risk was observed at the low-moderate PA level. The HR for cardiac death was reduced by half with 12.32% PA (177 min), and the HR for all-cause mortality was reduced by half with 11.92% PA (172 min). Subgroup analysis results indicated that older adults could benefit from PA and the range for achieving optimal benefits might be lower. CONCLUSIONS: PA monitoring may aid in long-term management of patients at high risk of SCD. More PA will generate better survival benefits, but even low-moderate PA is already good especially for older adults, which is relatively easy to achieve.

The feasibility and safety of left bundle branch pacing vs. right ventricular pacing after mid-long-term follow-up: a single-centre experience.

AIMS: The aim of this study is to prospectively assess the feasibility and safety of left bundle branch pacing (LBBP) when compared with right ventricular pacing (RVP) during mid-long-term follow-up in a large cohort. METHODS AND RESULTS: Patients (n = 554) indicated for pacemaker implantation were prospectively and consecutively enrolled and were non-randomized divided into LBBP group and RVP group. The levels of cTnT and N-terminal pro-B type natriuretic peptide were measured and compared within 2 days post-procedure between two groups. Implant characteristics, procedure-related complications, and clinical outcomes were also compared. Pacing thresholds, sensing, and impedance were assessed during procedure and follow-up. Left bundle branch pacing was feasible with a success rate of 94.8% with high incidence of LBB potential (89.9%), selective LBBP (57.8%), and left deviation of paced QRS axis (79.7%) with mean Sti-LVAT of 65.07 ± 8.58 ms. Paced QRS duration was significantly narrower in LBBP when compared with RVP (132.02 ± 7.93 vs. 177.68 ± 15.58 ms, P < 0.0001) and the pacing parameters remained stable in two groups during 18 months follow-up. cTnT elevation was more significant in LBBP when compared with RVP within 2 days post-procedure (baseline: 0.03 ± 0.03 vs. 0.02 ± 0.03 ng/mL, P = 0.002; 1 day post-procedure: 0.13 ± 0.09 vs. 0.04 ± 0.03 ng/mL, P < 0.001; 2 days post-procedure: 0.10 ± 0.08 vs. 0.03 ± 0.08 ng/mL, P < 0.001). The complications and cardiac outcomes were not significantly different between two groups. CONCLUSION: Left bundle branch pacing was feasible in bradycardia patients associated with stable pacing parameters during 18 months follow-up. Paced QRS duration was significantly narrower than that of RVP. Though cTnT elevation was more significant in LBBP within 2 days post-procedure, the complications, and cardiac outcomes were not significantly different between two groups.

Circulating metabolite profiles to predict response to cardiac resynchronization therapy.

BACKGROUND: Heart failure is associated with ventricular dyssynchrony and energetic inefficiency, which can be alleviated by cardiac resynchronization therapy (CRT) with approximately one-third of non-response rate. Thus far, there is no specific biomarker to predict the response to CRT in patients with heart failure. In this study, we assessed the role of the blood metabolomic profile in predicting the response to CRT. METHODS: A total of 105 dilated cardiomyopathy patients with severe heart failure who received CRT were included in our two-stage study. Baseline blood samples were collected prior to CRT implantation. The response to CRT was defined according to echocardiographic criteria. Metabolomic profiling of serum samples was carried out using ultrahigh performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry. RESULTS: Seventeen metabolites showed significant differences in their levels between responders and non-responders, and these metabolites were primarily involved in six pathways, including linoleic acid metabolism, Valine, leucine and isoleucine biosynthesis, phenylalanine metabolism, citrate cycle, tryptophan metabolism, and sphingolipid metabolism. A combination of isoleucine, tryptophan, and linoleic acid was identified as an ideal metabolite panel to distinguish responders from non-responders in the discovery set (n = 51 with an AUC of 0.981), and it was confirmed in the validation set (n = 54 with an AUC of 0.929). CONCLUSIONS: Mass spectrometry based serum metabolomics approach provided larger coverage of metabolome which can help distinguish CRT responders from non-responders. A combination of isoleucine, tryptophan, and linoleic acid may associate with significant prognostic values for CRT.

The mechanical effects of CRT promoting autophagy via mitochondrial calcium uniporter down-regulation and mitochondrial dynamics alteration.

The mechanism of cardiac resynchronization therapy (CRT) remains unclear. In this study, mitochondria calcium uniporter (MCU), dynamin-related protein-1 (DNM1L/Drp1) and their relationship with autophagy in heart failure (HF) and CRT are investigated. Thirteen male beagle's dogs were divided into three groups (sham, HF, CRT). Animals received left bundle branch (LBB) ablation followed by either 8-week rapid atrial pacing or 4-week rapid atrial pacing and 4-week biventricular pacing. Cardiac function was evaluated by echocardiography. Differentially expressed genes (DEGs) were detected by microarray analysis. General morphological changes, mitochondrial ultrastructure, autophagosomes and mitophagosomes were investigated. The cardiomyocyte stretching was adopted to imitate the mechanical effect of CRT. Cells were divided into three groups (control, angiotensin-II and angiotensin-II + stretching). MCU, DNM1L/Drp1 and autophagy markers were detected by western blots or immunofluorescence. In the present study, CRT could correct cardiac dysfunction, decrease cardiomyocyte's size, alleviate cardiac fibrosis, promote the formation of autophagosome and mitigate mitochondrial injury. CRT significantly influenced gene expression profile, especially down-regulating MCU and up-regulating DNM1L/Drp1. Cell stretching reversed the angiotensin-II induced changes of MCU and DNM1L/Drp1 and partly restored autophagy. CRT's mechanical effects down-regulated MCU, up-regulated DNM1L/Drp1 and subsequently enhanced autophagy. Besides, the mechanical stretching prevented the angiotensin-II-induced cellular enlargement.