Force Analysis Using Self-Expandable Valve Fluoroscopic Imaging: a way Through Artificial Intelligence.

This study aimed to develop a force analysis model correlating fluoroscopic images of self-expandable valves with stress distribution. For this purpose, a nonmetallic measuring device designed to apply diverse forces at specific positions on a valve stent while simultaneously measuring force magnitude was manufactured, obtaining 465 sets of fluorescent films under different force conditions, resulting in 5580 images and their corresponding force tables. Using the XrayGLM, a mechanical analysis model based on valve fluorescence images was trained. The accuracy of the image force analysis using this model was approximately 70% (50-88.3%), with a relative accuracy of 93.3% (75-100%). This confirms that fluoroscopic images of transcatheter aortic valve replacement (TAVR) valve stents contain a wealth of mechanical information, and machine learning can be used to train models to recognize the relationship between stent images and force distribution, enhancing the understanding of TAVR complications.

Outcomes of Upgrading to LBBP in CRT Nonresponders: A Prospective, Multicenter, Nonrandomized, Case-Control Study.

BACKGROUND: Cardiac resynchronization therapy (CRT) nonresponders account for nearly 30% of CRT candidates. Left-bundle branch pacing (LBBP) is an alternative to CRT. OBJECTIVES: This study aimed to evaluate the feasibility, clinical efficacy, and outcomes of upgrading to LBBP in CRT nonresponders, using propensity-score matching (PSM) analysis. METHODS: CRT nonresponders were defined as those with an implantable CRT-pacemaker or CRT-defibrillator for more than 12 months who remained nonresponsive (a decrease in left ventricular end-systolic volume of <15% or a left ventricular ejection fraction [LVEF] absolute increase of <5%) after optimal medical therapy and device optimization compared with baseline. In total, 145 CRT nonresponders were prospectively enrolled and randomly divided into 2 groups: upgraded to LBBP (n = 48), and continuing biventricular pacing (BVP) (control; n = 97). PSM was performed at a 1:1 ratio, and clinical evaluation and echocardiographic assessments were compared at baseline and follow-up in paired cohorts. The primary composite endpoint for clinical outcomes (heart failure-related rehospitalization events, all-cause death, or heart transplantation) was analyzed. RESULTS: Successful upgrading to LBBP was achieved in 48/49 patients (97.96%), with a significant decrease in QRS duration (P < 0.001). In the paired LBBP group, LVEF significantly increased (baseline: 29.75% ± 7.79%; 6 months: 37.78% ± 9.25% [P < 0.001]; 12 months: 38.84% ± 12.13% [P < 0.001]) with 21/44 patients (47.73%) classified as echocardiographically responsive, whereas in the BVP control group, no significant improvement was observed (29.55% ± 6.74% vs 29.22% ± 8.10%; P = 0.840). In a multivariate logistic regression model, LV end-diastolic volume and baseline LBBB QRS morphology were independent predictors of echocardiographic response after upgrading to LBBP. At a median 24 months, the primary composite endpoint was significantly lower in the LBBP group (HR: 0.31; 95% CI: 0.14-0.72; log-rank P = 0.007). CONCLUSIONS: Upgrading to LBBP is feasible and effective in achieving significant heart function improvement and better clinical outcomes in CRT nonresponders, making it a reasonable and promising pacing strategy. (LBBP in CRT Non-Response patients; ChiCTR1900028131).

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.

Electrical Resynchronization and Clinical Outcomes During Long-Term Follow-Up in Intraventricular Conduction Delay Patients Applied Left Bundle Branch Pacing-Optimized Cardiac Resynchronization Therapy.

BACKGROUND: Left bundle branch-optimized cardiac resynchronization therapy (LOT-CRT) has shown encouraging results for QRS duration reduction and heart function improvement. However, the feasibility and efficacy of LOT-CRT have not been well established in intraventricular conduction delay patients. This study aims to assess and compare the efficacy and clinical outcome of CRT based on left bundle branch pacing, combined with coronary sinus left ventricular pacing (LOT-CRT) with CRT via biventricular pacing (BiV-CRT) in intraventricular conduction delay patients indicated for CRT. METHODS: Consecutive patients with intraventricular conduction delay and CRT indications were assigned nonrandomized to LOT-CRT (n=30) or BiV-CRT (n=55). Addition of the left bundle branch pacing (or coronary venous) lead was at the discretion of the implanting physician guided by suboptimal paced QRS complex and on clinical grounds. Echocardiographic parameters and clinical characteristics were accessed at baseline and during 2-years' follow-up. RESULTS: Success rate for LOT-CRT and BiV-CRT was 96.8% and 96.4%. LOT-CRT had greater reduction of QRS duration compared with BiV-CRT (42.7±17.4 ms versus 21.9±21.5 ms; P<0.001). Higher left ventricular ejection fraction was also achieved in LOT-CRT than BiV-CRT at 6-month (36.7±9.8% versus 30.5±6.4%; P<0.05), 12-month (34.8±7.6% versus 30.3±6.2%; P<0.05), 18-month (36.3±7.9% versus 28.1±6.6%; P<0.005), and 24-month follow-up (37±9.5% versus 30.5±7%; P<0.05). Adverse clinical outcomes including heart failure rehospitalization and mortality were lower in LOT-CRT group for 24 months follow-up (hazard ratio, 0.33; P=0.035). CONCLUSIONS: LOT-CRT improves ventricular electrical synchrony and may provide greater clinical outcomes as compared with BiV-CRT in intraventricular conduction delay patients. These findings need further evaluation in future randomized controlled trials.

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.

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.

Left Bundle Branch Pacing Versus Biventricular Pacing for Acute Cardiac Resynchronization in Patients With Heart Failure.

BACKGROUND: Left bundle branch pacing (LBBP) has emerged as an alternative to biventricular pacing (BVP) for delivering cardiac resynchronization therapy. We sought to compare the acute improvement of electrical and mechanical synchrony, and hemodynamics between LBBP and BVP in patients with heart failure and left bundle branch block. METHODS: LBBP and BVP were performed and compared in a crossover fashion in patients with heart failure and left bundle branch block undergoing cardiac resynchronization therapy implantation. Electrical synchrony was assessed by QRS duration and area, mechanical synchrony by the SD of time to peak velocity of 12 left ventricular segments (Ts-SD) and interventricular mechanical delay, and hemodynamics by the maximum rate of left ventricular pressure rise (dP/dtmax). RESULTS: Twenty-one patient with heart failure and left bundle branch block (mean age 67±10 years, 48% male, and 90% nonischemic cause) were included. Both LBBP and BVP provided significant improvements in electrical and mechanical synchrony, and hemodynamics compared to the baseline. Compared with BVP, LBBP achieved a larger reduction in QRS duration (-11 ms [95% CI, -17 to -4 ms]; P=0.003) and QRS area (-85 µVs [95% CI, -113 to -56 µVs]; P<0.001); LBBP achieved a greater decrease in Ts-SD (-14 ms [95% CI, -21 to -7 ms]; P=0.001), with no significant difference in interventricular mechanical delay (-2 ms [95% CI, -13 to 8 ms]; P=0.63). The increase in dP/dtmax from LBBP was significantly higher than that from BVP (6% [95% CI, 2%-9%]; P=0.002). CONCLUSIONS: LBBP delivers greater acute electrical and mechanical resynchronization and hemodynamic improvement than BVP in predominantly nonischemic heart failure patients with left bundle branch block. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04505384.

Translocation of gasdermin D induced mitochondrial injury and mitophagy mediated quality control in lipopolysaccharide related cardiomyocyte injury.

BACKGROUNDS: Inflammation underlies the mechanism of different kinds of heart disease. Cytoplasmic membrane localized N-terminal fragment of gasdermin-D (GSDMD-N) could induce inflammatory injury to cardiomyocyte. However, effects and dynamic changes of GSDMD during the process of lipopolysaccharide (LPS) related inflammatory stress induced cardiomyocyte injury are barely elucidated to date. In this study, LPS related cardiomyocyte injury was investigated based on potential interaction of GSDMD-N induced mitochondrial injury and mitophagy mediated mitochondria quality control. METHODS: HL-1 cardiomyocytes were treated with LPS and Nigericin to induce inflammatory stress. The dual-fluorescence-labelled GSDMD expressed HL-1 cardiomyocytes were constructed to study the translocation of GSDMD. The mitochondrial membrane potential (MMP) was measured by JC-1 staining. Mitophagy and autophagic flux were recorded by transmission electron microscopy and fluorescent image. RESULTS: GSDMD-N showed a time-dependent pattern of translocation from mitochondria to cytoplasmic membrane under LPS and Nigericin induced inflammatory stress in HL-1 cardiomyocytes. GSDMD-N preferred to localize to mitochondria to permeablize its membrane and dissipate the MMP. This effect couldn't be reversed by cyclosporine-A (mPTP inhibitor), indicating GSDMD-N pores as alternative mechanism underlying MMP regulation, in addition to mitochondrial permeability transition pore (mPTP). Moreover, the combination between GSDMD-N and autophagy related Microtubule Associated Protein 1 Light Chain 3 Beta (LC3B) was verified by co-immunoprecipitation. Besides, mitophagy alleviating GSDMD-N induced mitochondrial injury was proved by pre-treatment of autophagy antagonist or agonist in GSDMD-knock out or GSDMD-overexpression cells. A time-dependent pattern of GSDMD translocation and mitochondrial GSDMD targeted mitophagy were verified. CONCLUSION: Herein, our study confirmed a crosstalk between GSDMD-N induced mitochondrial injury and mitophagy mediated mitochondria quality control during LPS related inflammation induced cardiomyocyte injury, which potentially facilitating the development of therapeutic target to myocardial inflammatory disease. Our findings support pharmaceutical intervention on enhancing autophagy or inhibiting GSDMD as potential target for inflammatory heart disease treatment.

Role of the Gut Microbiota in Glucose Metabolism During Heart Failure.

Background: Blood glucose disorders are prevalent in heart failure, while the influence of the gut microbiota on this process remains unclear. Here, we used heart failure model mice and fecal microbiota transplantation (FMT) mice to evaluate the effect of the gut microbiota on the regulation of blood glucose during heart failure. Methods: Thoracic aortic constriction (TAC) surgery was performed in a heart failure model, while an antibiotic cocktail was used to eliminate the microbiota to establish a germ-free (GF) model. Blood glucose, insulin, and glucagon levels were measured, and an intraperitoneal glucose tolerance test (IPGTT) was performed. 16S rRNA sequencing and metabolomics were used to evaluate the changes in gut microbiota structure and metabolism induced by TAC. Another group of FMT mice was established to observe the effect of the gut microbiota on host metabolism. Results: After microbiota clearance, the glucagon concentration, the homeostasis model assessment for insulin resistance (HOMA-IR), and the area under the curve (AUC) of the IPGTT were decreased significantly in the TAC germ-free (TAC-GF) group in the third month as compared to the other groups. 16S rRNA sequencing indicated that TAC surgery affected the gut microbiota structure, and fecal metabolomics suggested that noradrenaline and adrenaline levels were higher in the TAC group than in the sham group. The FMT mice transplanted with the feces of the TAC (FMT-TAC) mice displayed a higher AUC of IPGTT, accompanied by a higher glucagon level, insulin level, and HOMA-IR than those of the mice in the other groups. The serum metabolomics of the FMT-TAC group showed that noradrenaline levels were significantly higher than those of the FMT-sham group. Conclusion: The gut microbiota and its metabolism were altered during heart failure, which increased blood glucose and glucagon in the host.

Current of injury is an indicator of lead depth and performance during left bundle branch pacing lead implantation.

BACKGROUND: Monitoring of lead depth is crucial to achieve left bundle branch pacing (LBBP) with a low capture threshold and avoid septal perforation, but lacks informative approach. OBJECTIVE: We aimed to prospectively assess the predictive value of current of injury on the occurrence of inadequate left bundle branch (LBB) capture threshold and acute septal perforation. METHODS: Consecutive patients who received LBBP were enrolled. ST-segment elevation ≥ 25% of intrinsic R-wave amplitude on the unipolar intracardiac electrogram was defined as a sign of distinct current of injury. An LBB capture threshold of <1.5 V/0.5 ms was considered acceptable. RESULTS: LBBP was attempted 513 times in 212 patients. The LBB capture threshold was more likely to improve to an acceptable level after 10 minutes in leads with initial (33 of 47 vs 0 of 8, with vs without) and residual (29 of 33 vs 4 of 14, with vs without) current of injury recorded on the tip electrode (P < .0001). Lead perforation during the procedure has occurred in 11 patients who had no current of injury noted on the tip electrode. The ratio of current of injury recorded on the tip electrode to that on the ring electrode was correlated to the lead depth determined by sheath angiography (Spearman correlation coefficient -0.624; P < .0001), and microperforation is highly possible when the ratio is decreased to <1 (sensitivity 100%; specificity 96.6%). CONCLUSION: Current of injury is a useful tool in forecasting LBBP lead depth and septal perforation, and it could facilitate the decision-making process when the initial LBB capture threshold is undesirable.

Evaluation of electrophysiological characteristics and ventricular synchrony: An intrapatient-controlled study during His-Purkinje conduction system pacing versus right ventricular pacing.

OBJECTIVES TO BACKGROUND: To compare electromechanical ventricular synchrony when pacing from different sites, including right ventricular apex pacing (RVAP), right ventricular septum pacing (RVSP), His bundle pacing (HBP), left bundle branch pacing (LBBP), and RVSP during unipolar pacing from the ring electrode of LBBP lead (RVSPring ) in each patient and evaluate the correlations between electrophysiological characteristics and ventricular synchrony. METHODS: Twenty patients with complete atrioventricular block indicated for dual-chamber pacemaker implantation were included in the study. Unipolar pacing at different sites, including RVAP, RVSP, HBP, LBBP, and RVSPring , was successively performed in each patient. The pacing characteristics and echocardiogram parameters were collected and compared among intrinsic rhythm and pacing at different sites. RESULTS: Similar to HBP (114.84 ± 18.67 ms), narrower paced QRSd was found in LBBP (116.15 ± 11.60 ms) as compared to RVSPring (135.11 ± 13.68 ms), RVSP (141.65 ± 14.26 ms), and RVAP (160.15 ± 19.35 ms) (p < .001). LBBP showed comparable pacing parameters to RVAP or RVSP and was significantly better than HBP, with maintained cardiac function. TS-12-SD was significantly improved in LBBP (41.80 ± 20.97 ms) than RVAP (69.70 ± 32.42 ms, p = .003) and RVSP (63.30.56 ± 32.53 ms, p = .018) but similar to HBP (51.50 ± 25.67 ms, p = .283) or RVSPring (57.80 ± 25.65 ms, p = .198). Among these pacing strategies, negative values of interventricular mechanical delay (IVMD) were only identified in LBBP (-19.25 ± 18.43 ms), significantly different from RVAP (35.00 ± 30.72 ms), RVSP (22.85 ± 22.05 ms), HBP (5.20 ± 18.64 ms), and RVSPring (16.00 ± 26.76 ms (all p < .05). Using Pearson's analysis, Sti-LVAT was positively correlated with QRS duration, IVMD, TS-12-SD, LVEDV, and LVESV, while a negative relationship could be observed for left ventricular ejection fraction. CONCLUSIONS: His-Purkinje conduction system pacing (HPCSP) achieved better electrical and mechanical synchrony than conventional RV pacing. For interventricular synchrony, only LBBP initiated earlier LV activation than RV, in accordance with the right bundle branch block (RBBB) pattern of paced QRS during LBBP. Sti-LVAT might be a good parameter correlating with LV systolic function and mechanical synchrony.

Risk factors of pacing dependence and cardiac dysfunction in patients with permanent pacemaker implantation.

AIMS: Right ventricular pacing (RVP) dependence could impair left ventricular ejection fraction (LVEF). This study aimed to illuminate the relationship between RVP proportion and LVEF, as well as disclosing independent predictors of RVP dependence. METHODS AND RESULTS: Patients indicated for permanent pacemaker implantation were included (2016-2020). The ventricular pacing lead was placed in right ventricular apex or septum. Pacing mode programming followed universal standard. Electrocardiographic, echocardiographic, and serological parameters were collected. RVP dependence was defined according to its influence on LVEF. This study was of case-control design. Included patients were matched by potentially confounding factors through propensity score matching. A total of 1183 patients were included, and the mean duration of follow-up was 24 months. Percentage of RVP < 80% hardly influenced LVEF; however, LVEF tended to decrease with higher RVP proportion. High degree/complete atrioventricular block (AVB) [odds ratio (OR) = 5.71, 95% confidence interval (CI): 3.66-8.85], atrial fibrillation (AF) (OR = 2.04, 95% CI: 1.47-2.82), percutaneous coronary intervention (PCI) (OR = 2.89, 95% CI: 1.24-6.76), maximum heart rate (HRmax ) < 110 b.p.m. (OR = 2.74, 95% CI: 1.58-4.76), QRS duration > 120 ms (OR = 2.46, 95% CI: 1.42-4.27), QTc interval > 470 ms (OR = 2.01, 95% CI: 1.33-3.05), and pulmonary artery systolic pressure (PASP) > 40 mmHg (OR = 1.93, 95% CI: 1.46-2.56) were proved to predict RVP dependence. CONCLUSIONS: High RVP percentage (>80%) indicating RVP dependence significantly correlates with poor prognosis of cardiac function. High degree/complete AVB, AF, ischaemic aetiology, PCI history, HRmax  < 110 b.p.m., QRS duration > 120 ms, QTc interval > 470 ms, and PASP > 40 mmHg were verified as independent risk factors of RVP dependence.

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.

Prediction of response after cardiac resynchronization therapy with machine learning.

AIMS: Nearly one third of patients receiving cardiac resynchronization therapy (CRT) suffer non-response. We intend to develop predictive models using machine learning (ML) approaches and easily attainable features before CRT implantation. METHODS AND RESULTS: The baseline characteristics of 752 CRT recipients from two hospitals were retrospectively collected. Nine ML predictive models were established, including logistic regression (LR), elastic network (EN), lasso regression (Lasso), ridge regression (Ridge), neural network (NN), support vector machine (SVM), random forest (RF), XGBoost and k-nearest neighbour (k-NN). Sensitivity, specificity, precision, accuracy, F1, log-loss, area under the receiver operating characteristic (AU-ROC), and average precision (AP) of each model were evaluated. AU-ROC was compared between models and the latest guidelines. Six models had an AU-ROC value above 0.75. The LR, EN and Ridge models showed the highest overall predictive power compared with other models with AU-ROC at 0.77. The XGBoost model reached the highest sensitivity at 0.72, while the highest specificity was achieved by Ridge model at 0.92. All ML models achieved higher AU-ROCs that those derived from the latest guidelines (all P < 0.05). The effect size analysis identified left bundle branch block, left ventricular end-systolic diameter, and history of percutaneous coronary intervention as the most crucial predictors of CRT response. An online tool to facilitate the prediction of CRT response is freely available at http://www.crt-response.com/. CONCLUSIONS: ML algorithms produced efficient predictive models for evaluation of CRT response with features before implantation. Tools developed accordingly could improve the selection of CRT candidates and reduce the incidence of non-response.

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.

Left ventricular-only fusion pacing versus cardiac resynchronization therapy in heart failure patients: A randomized controlled trial.

BACKGROUND: It is unclear whether clinical benefits of cardiac resynchronization can be achieved by pacing only the left ventricle. HYPOTHESIS: We aimed to compare the effect of a novel adaptive left ventricular-only fusion pacing (LVP) on ventricular function with conventional biventricular pacing (BVP) in cardiac resynchronization therapy (CRT) indicated patients. METHODS: This prospective, randomized, multicenter study enrolled CRT-indicated patients with PR interval ≤ 200 ms who were randomized in the adaptive LVP group (using the AdaptivCRT™ algorithm with intentional non-capture right ventricular pacing) or the echocardiography-optimized BVP group. Cardiac function and echocardiography were evaluated at baseline and follow-ups. CRT super response was defined as two-fold or more increase of left ventricular ejection fraction (LVEF) or final LVEF >45%, and LV end-systolic volume (LVESV) decrease >15%, and New York Heart Association (NYHA) class improved by at least one level. RESULTS: Sixty-three patients were enrolled in the study (LVP = 34 vs. BVP = 29). At 6-month follow-up, significant improvements in LVEF, LVESV, and NYHA class were observed in both groups. The CRT super response rate was significantly higher in patients with high-percentage adaptive LV-only pacing in LVP group (68.4%) than in BVP group (36.4%, p = .04). CONCLUSIONS: Adaptive LV-only pacing was comparable to BVP in improving cardiac function and clinical condition in CRT-indicated patients. This finding raises the possibility that an adaptive LVP algorithm with appropriate right ventricular sensing to fuse with intrinsic right ventricular activation in a two-lead (right atrium and left ventricle) device may provide clinical benefit in a subset of CRT patients with intact atrioventricular conduction.

Procedure-Related Complications of Left Bundle Branch Pacing: A Single-Center Experience.

Background: Although left bundle branch pacing (LBBP) has emerged as a novel physiological pacing strategy with a low and stable threshold, its safety has not been well-documented. In the present study, we included all the patients with procedure-related complications at our centre to estimate these LBBP cases with unique complications. Methods: We enrolled 612 consecutive patients who received the procedure in Zhongshan Hospital, Fudan University, between January 2018 and July 2020. Regular follow-ups were conducted (at 1, 3, and 6 months in the first year and every 6-12 months from the second year), and the clinical data of the patients with complications were collected and analyzed. Results: With a mean follow-up period of 12.32 ± 5.21 months, procedure-related complications were observed in 10 patients (1.63%) that included two postoperative septum perforations (2/612, 0.33%), two postoperative lead dislodgements (2/612, 0.33%), four intraoperative septum injuries (4/612, 0.65%), and two intraoperative lead fractures (2/612, 0.33%). Pacing parameters were stable during follow-up, and no major complications were observed after lead repositioning in the cases of septum perforation and lead dislodgement. Conclusion: The incidence of procedure-related complications for LBBP, namely postoperative septum perforation, postoperative lead dislodgement, intraoperative septum injury, and intraoperative lead fracture, were low. No adverse clinical outcomes were demonstrated after successful repositioning of the lead and appropriate treatment.

Protective effects of cardiac resynchronization therapy in a canine model with experimental heart failure by improving mitochondrial function: a mitochondrial proteomics study.

PURPOSE: Cardiac resynchronization therapy (CRT) is well acknowledged as an effective treatment for dyssynchronous heart failure. However, the molecular mechanism is unclear to date. Mitochondrial dysfunction and impaired energetic metabolism are two important mechanisms that lead to heart failure. Therefore, we aim to screen the changes of mitochondria-associated proteins and signaling pathways involved in heart failure and CRT treatment. METHODS: A total of 24 beagle dogs were randomly assigned into control (CON), heart failure (HF), or CRT group. Myocardial mitochondria from the free wall of left ventricle was extracted for isobaric tags for relative and absolute quantitation (iTRAQ) labeling coupled with two-dimensional liquid chromatography tandem mass spectrometry analysis (2DLC-MS/MS). RESULTS: A total of 2190 proteins were identified, among which 234 proteins were differentially expressed in HF compared with CON group, 151 proteins were differentially expressed in CRT compared with HF group. A total of 192 of the 234 differentially expressed proteins in HF group were changed oppositely by CRT treatment, and 128 of the 151 CRT-induced differentially expressed proteins showed opposite trend of expression to HF/CON. Gene Ontology analysis of the 128 proteins revealed that 16 were localized in mitochondria, 17 were associated with calcium signaling, and 7 could be secreted extracellularly for cell-to-cell signaling. Calpain-1 (CAPN1), which is localized to mitochondria and related to calcium signaling, was upregulated in HF and downregulated after CRT treatment. CRT treatment also improved mitochondrial morphology and function and reduced collagen areas of both interstitial and perivascular fibrosis. CONCLUSIONS: CRT treatment significantly improved cardiac function, reduced myocardial fibrosis, and enhanced mitochondrial function in the failing heart through CAPN1 downregulation.

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.