Yangang Su

Background: While cardiac resynchronization therapy is effective in dyssynchronous heart failure, suboptimal response remains frequent. The acute hemodynamic profile of different left bundle‐branch (LBB) area pacing modalities is poorly defined. Moreover, atrioventricular optimization guided by QRS duration (QRSd) may not yield the greatest hemodynamic benefit. Methods: Twenty‐four patients with heart failure, reduced ejection fraction, and LBB block underwent sequential testing of right ventricular septal pacing, left ventricular septal pacing, nonselective LBB pacing, and selective LBB pacing during cardiac resynchronization therapy implantation in a prospective, within‐subject physiological study. At each modality, electrical end points were QRSd and vectorcardiographic QRS area; hemodynamics were assessed with beat‐to‐beat systolic blood pressure (SBP). The atrioventricular interval producing maximal SBP improvement was compared with that producing the narrowest QRSd. Results: LBB area pacing modalities significantly reduced QRSd , compared with right ventricular septal pacing (nonselective LBB pacing, 114.0±16.8 milliseconds; selective LBB pacing , 118.4±14.1 milliseconds; left ventricular septal pacing, 124.6±16.0 milliseconds; right ventricular septal pacing, 144.4±27.6 milliseconds; all P P <0.05). Across modalities, the atrioventricular interval that maximized ΔSBP was consistently shorter than that minimizing QRSd (mean difference, 18–29 milliseconds). Conclusions: Selective LBB pacing yields the greatest acute hemodynamic benefit, and the hemodynamic‐optimal atrioventricular interval is shorter than the electrical‐optimal atrioventricular interval, suggesting that modest atrioventricular interval shortening after electrical optimization may better maximize hemodynamics. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT07032064.

Aims: Accurate prediction of the clinical course in implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D) patients is crucial, as their disease progression varies significantly due to comorbidities and individual characteristics. Methods: This retrospective study included 3321 patients from four hospitals in China, with 3207 for model development and internal validation and 114 for external testing. Five machine learning (ML) models were evaluated using the C-index, time-dependent AUROC, and Brier score. Decision curve analysis (DCA) assessed clinical utility, while Kaplan–Meier curves stratified patients into high-, intermediate-, and low-risk groups. SHAP analysis identified key predictors and explained model outputs. Results: The Random Survival Forest (RSF) model demonstrated favorable numerical performance across multiple evaluation metrics, achieving the highest time-dependent AUROC (0.74, 0.74) and C-index (0.71, 0.70) in internal and external test sets. It also had the lowest time-dependent Brier score (0.17) in the internal test and ranked second (0.13) in the external test. DCA demonstrated numerically higher net benefit for the RSF model across evaluated threshold probabilities. Kaplan–Meier curves revealed distinct survival trajectories, with high-risk patients showing significantly higher mortality than low-risk patients (HR: 4.50, 95% CI: 3.10–6.55, p < 0.0001), while intermediate-risk patients also had increased mortality (HR: 2.49, 95% CI: 1.69–3.68, p < 0.0001). LVEDD was the most influential predictor of mortality. Conclusions: The RSF survival model enables individualized, time-resolved prediction of all-cause mortality risk in ICD and CRT-D patients, supporting risk stratification and future evaluation of clinical utility, while requiring cautious interpretation of longer-term predictions due to limited numbers at risk.

Background and purpose: The real-world safety and performance of the Micra VR leadless pacemaker have been well-established by previous clinical trials. However, there is little clinical data from these studies specific to patients in China. The purpose of this study was to characterize the safety and performance of the Micra VR leadless pacemaker in a Chinese cohort. Methods: The primary endpoints of the Micra Acute Performance Greater China (MAP China) study were acute (≤30 days post-implant) and 12-month major complication rate following implantation of the Micra VR leadless pacemaker. Electrical performance was characterized from the time of implant through 12-month follow-up. Patient baseline and procedural characteristics and major complications were compared to the China pre-market and global Post-Approval Registry studies. Results: A total of 100 patients were enrolled and successfully implanted with the Micra VR system between June 2021 and October 2022 across 11 sites in mainland China. Average follow-up was 11.1 ± 4.1 months. One major complication was reported in 1 patient within 30 days from the time of implant for an acute and 12-month complication rate of 1.0% (95% confidence interval: 0.025%–5.446%). Risk of major complications was in line with the China pre-market and global Post-Approval Registry studies. Conclusion: The Micra VR leadless pacemaker had high implant success and low major complication rates in patients from China, in agreement with the China pre-market and global Post-Approval Registry studies.

Background: Unexplained syncope and palpitations are common chief complaints in the outpatient department of cardiology. Their sporadic and unpredictable poses significant diagnostic challenges. Implantable cardiac monitors (ICMs) can monitor arrhythmia events efficiently, and can overcome the shortcomings of traditional electrocardiogram (ECG) detection tools such as Holter. However, the high cost of imported ICM devices limits accessibility for patients in China. The MA01‐100 (Singular Medical, Suzhou, China), the first domestically developed ICM, may offer a cost‐effective alternative. This study aimed to evaluate the safety and efficacy of the MA01‐100 compared with standard surface electrocardiography (ECG) for arrhythmia monitoring in Chinese patients. Methods: A prospective, paired design trial was conducted across six hospitals in China. Sixty‐four participants underwent implantation of the MA01‐100 ICM device. As the self‐control group, patients were also assessed using a surface ECG at implantation, and 30‐ and 90‐day follow‐ups. The primary efficacy endpoints were the sensitivity and positive predictive value (PPV) of R wave detection at 30 days post‐implantation. Secondary endpoints included R wave amplitude stability, QRS complex morphology consistency, arrhythmia event detection rate, arrhythmia event identification accuracy, clinical performance evaluation of the programmer, and remote transmission function assessment. Safety was evaluated by the incidence rates of major adverse events (MAEs), serious adverse events (SAEs), and device defects within 3 months of follow‐up. Results: All 64 patients who met the inclusion criteria were enrolled in the trial. They underwent successful cardiac monitor implantation with acceptable sensitivity and PPV of R wave detection. The mean sensitivity was 99.98 ± 0.10%, with a minimum of 99.34%. The two‐sided 95% confidence interval (CI) for the compliance rate was (94.40%–100.00%). The mean PPV was 99.94 ± 0.35%, with a minimum of 97.35%. The two‐sided 95% CI for the compliance rate was (94.40%–100.00%). Two patients (3.1%) experienced mild implantation site infections; no device defects or SAEs were observed. All pre‐defined efficacy and safety benchmarks were met. Conclusion: This study provides the first prospective, multicenter clinical evaluation of the safety and efficacy of an intracardiac monitor (ICM) independently developed in China. It systematically validated the device's clinical performance, thereby filling the gap in China's ICM field across the entire chain of “independent development–clinical validation–translational application.” The results demonstrate that the ICM meets the requirements for clinical use, providing new support for improving the accessibility of arrhythmia diagnostic services in China and offering a reference for formulating globally cost‐effective cardiac monitoring strategies.

Mixed lineage kinase 3 (MLK3), a member of the MAP3K family, is known to participate in cellular stress and inflammatory responses, but its role in neutrophil-mediated myocardial ischemia–reperfusion (I/R) injury remains unclear. In this study, we investigated the function and downstream signaling of MLK3 in neutrophils using genetically modified mouse models with neutrophil-specific MLK3 knockout or overexpression. MLK3 deficiency in neutrophils reduced infarct size, improved cardiac function, and decreased neutrophil infiltration, NET formation, and pro-inflammatory cytokine release following I/R. Transcriptomic profiling revealed that MLK3 promotes the expression of the antimicrobial peptide CRAMP by stabilizing and activating the transcription factor C/EBPβ. Administration of exogenous CRAMP abolished the protective effects of MLK3 deletion, confirming its functional relevance. Furthermore, treatment with CEP-1347, a small-molecule MLK3 inhibitor, attenuated myocardial injury, reduced apoptosis, and limited adverse remodeling in vivo. In acute myocardial infarction (AMI) patients, elevated levels of phosphorylated MLK3 (pMLK3) in circulating neutrophils were associated with increased levels of MPO-DNA, cTnT, and CK-MB, as well as a trend toward higher rates of cardiovascular rehospitalization. These findings identify a neutrophil-intrinsic MLK3–C/EBPβ–CRAMP axis that amplifies myocardial inflammation and injury, and suggest MLK3 as a promising therapeutic target and potential biomarker for ischemic heart disease.

Inflammation-induced cardiac dysfunction, driven by an abnormal immune response, significantly contributes to sepsis-related mortality. Controlling excessive pro-inflammatory cytokine production by immune cells remains a significant challenge. This study investigated the role of N-acetyltransferase 10 (NAT10) in macrophage activation and its contribution to inflammation-induced cardiac dysfunction. Using bone marrow-derived macrophages and an endotoxemia mouse model, we found that NAT10 is significantly upregulated in response to lipopolysaccharide (LPS) due to the deubiquitinating enzyme USP39, which stabilizes the NAT10 protein. ac4C RNA sequencing identified ETS2 as a direct target of NAT10, where the ac4C modification enhanced ETS2 mRNA stability and translation, promoting a pro-inflammatory phenotype in macrophages. NAT10 deficiency reduces LPS-induced macrophage activation and cytokine production, improving cardiac function in mice. Pharmacological inhibition of NAT10 using remodelin produced similar protective effects. Our findings reveal a novel post-transcriptional pathway and highlight the therapeutic potential of targeting NAT10 to mitigate inflammation-induced cardiac injury in endotoxemia

Background: Left bundle branch area pacing (LBBAP) emerges as an alternative to traditional right ventricular pacing, demonstrating safety and feasibility through superior access for implantation. Case summary: An 89-year-old female, with a prior history of pacemaker pocket infection and a tricuspid endocarditis during follow-up, was referred to our hospital for management due to a sinus arrest. The patient underwent pacemaker removal due to a pocket infection in the right subclavian area, necessitating tricuspid valvuloplasty for infective endocarditis. Venography revealed occlusion in the left brachiocephalic vein. Subsequently, LBBAP pacemaker implantation via the right iliac vein was performed, with follow-up indicating proper functioning of the pacing system. Discussion: The feasibility of the right iliac vein access for LBBAP implantation is highlighted, demonstrating good stability and offering a practical alternative. This approach mitigates unnecessary risks associated with thoracotomy and epicardial lead placement, providing a safer and effective option for cardiac pacing.

Purpose Macrophage-mediated inflammation plays a crucial role in the pathophysiological process of myocardial ischemia/reperfusion (I/R) injury. Recent studies have highlighted the importance of mitochondrial function and inflammasome activation in the inflammatory process. Kirenol, a well-known natural compound, has been shown to regulate inflammation in various diseases. This study investigated whether Kirenol could exert anti-inflammatory effects on macrophages during myocardial I/R injury. Methods Mouse myocardial I/R models were established by 45 min of ischemia followed by 24 h of reperfusion. Saline or Kirenol treatment was administered. In vivo assessments included the evaluation of cardiac function, infarcted area, and immune cell infiltration. Subsequently, bone marrow-derived macrophages (BMDMs) were isolated, and mitochondrial function and pyroptosis were assessed. Furthermore, the study compared the cardioprotective effects of Kirenol with a specific NOX1/NOX4 inhibitor, GKT137831. Results Kirenol gavage improved cardiac function, decreased infarct area, and alleviated inflammatory infiltration in mice subjected to myocardial I/R injury. Mechanistically, Kirenol inhibited NOX1 and NOX4 and enhanced mitochondrial function, ultimately attenuating the pyroptosis of macrophages. The therapeutic effects of Kirenol and GKT137831 were not significantly different. Conclusion This study demonstrates that Kirenol mitigates myocardial I/R injury by inhibiting NOX1 and NOX4, restoring mitochondrial function, and ameliorating macrophage pyroptosis.