Circumferential Pulmonary Vein Isolation With vs Without Additional Low-Voltage-Area Ablation in Older Patients With Paroxysmal Atrial Fibrillation

JAMA Cardiology · 2023 · 65 citations

• Medicine
• Cardiology
• Internal medicine

Importance: The overall success rate of circumferential pulmonary vein isolation (CPVI) treatment in patients with paroxysmal atrial fibrillation (AF) remains suboptimal, especially in older patients. Objective: To explore the incremental benefit of low-voltage-area ablation after CPVI in older patients with paroxysmal AF. Design, Setting, and Participants: This randomized clinical trial was an investigator-initiated trial to compare the efficacy of additional low-voltage-area ablation beyond CPVI vs CPVI alone in older patients with paroxysmal AF. Participants were patients aged 65 to 80 years with paroxysmal AF who were referred for catheter ablation. They were enrolled in 14 tertiary hospitals in China from April 1, 2018, to August 3, 2020, and follow-up occurred through August 15, 2021. Interventions: Patients were randomized (1:1) to undergo CPVI plus low-voltage-area ablation or CPVI alone. Low-voltage areas were defined as areas with amplitude less than 0.5 mV in more than 3 adjacent points. If low-voltage areas existed, additional substrate ablation was performed in the CPVI plus group but not the CPVI alone group. Main Outcomes and Measures: The primary end point of the study was freedom from atrial tachyarrhythmia as documented by electrocardiogram during a clinical visit or lasting longer than 30 seconds during Holter recordings occurring after a single ablation procedure. Results: Among 438 patients who were randomized (mean [SD] age, 70.5 [4.4] years; 219 men [50%]), 24 (5.5%) did not complete the blanking period and were not included for efficacy analysis. After a median follow-up of 23 months, the recurrence rate of atrial tachyarrhythmia was significantly lower in the CPVI plus group (31/209 patients, 15%) compared with the CPVI alone group (49/205, 24%; hazard ratio [HR], 0.61; 95% CI, 0.38-0.95; P = .03). In subgroup analyses, among all patients with low-voltage area, CPVI plus substrate modification was associated with a 51% decreased risk of ATA recurrence compared with CPVI alone (HR, 0.49; 95% CI, 0.25-0.94; P = .03). Conclusions and Relevance: This study found that additional low-voltage-area ablation beyond CPVI decreased the ATA recurrence in older patients with paroxysmal AF compared with CPVI alone. Our findings merit further replication by larger trials with longer follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT03462628.

Prediction Models for Conversion From Mild Cognitive Impairment to Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Frontiers in Aging Neuroscience · 2022 · 96 citations

• Medicine
• Internal medicine
• Psychology

Background and Purpose: Alzheimer's disease (AD) is a devastating neurodegenerative disorder with no cure, and available treatments are only able to postpone the progression of the disease. Mild cognitive impairment (MCI) is considered to be a transitional stage preceding AD. Therefore, prediction models for conversion from MCI to AD are desperately required. These will allow early treatment of patients with MCI before they develop AD. This study performed a systematic review and meta-analysis to summarize the reported risk prediction models and identify the most prevalent factors for conversion from MCI to AD. Methods: We systematically reviewed the studies from the databases of PubMed, CINAHL Plus, Web of Science, Embase, and Cochrane Library, which were searched through September 2021. Two reviewers independently identified eligible articles and extracted the data. We used the Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies (CHARMS) checklist for the risk of bias assessment. Results: In total, 18 articles describing the prediction models for conversion from MCI to AD were identified. The dementia conversion rate of elderly patients with MCI ranged from 14.49 to 87%. Models in 12 studies were developed using the data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). C-index/area under the receiver operating characteristic curve (AUC) of development models were 0.67-0.98, and the validation models were 0.62-0.96. MRI, apolipoprotein E genotype 4 (APOE4), older age, Mini-Mental State Examination (MMSE) score, and Alzheimer's Disease Assessment Scale cognitive (ADAS-cog) score were the most common and strongest predictors included in the models. Conclusion: In this systematic review, many prediction models have been developed and have good predictive performance, but the lack of external validation of models limited the extensive application in the general population. In clinical practice, it is recommended that medical professionals adopt a comprehensive forecasting method rather than a single predictive factor to screen patients with a high risk of MCI. Future research should pay attention to the improvement, calibration, and validation of existing models while considering new variables, new methods, and differences in risk profiles across populations.

Silk‐Inspired In Situ Hydrogel with Anti‐Tumor Immunity Enhanced Photodynamic Therapy for Melanoma and Infected Wound Healing

Advanced Functional Materials · 2021 · 117 citations

• Materials science
• Cancer research
• Medicine

Abstract Easy cancer recurrence and wound infections have been clinical challenges after surgical treatment of melanoma. Herein, a silk‐inspired in situ gelation system containing methacrylated silk fibroin (SF) and chlorine e6 for improved cancer therapy with enhanced wound healing is developed. Favored by the macrophage recruitment capacity of the SF hydrogel, promising antitumor immune responses can be turned “on” via near infrared irradiation in a controllable manner to achieve combination therapy with photodynamic therapy to significantly suppress melanoma recurrence. Moreover, the effective photodynamic antibacterial activity of this bioactive system with the capacity of light‐controllable modulating macrophage phenotype promotes remarkable tissue ingrowth with hair follicle regeneration for Staphylococcus aureus infected wound healing. Thus, this multifunctional silk‐based hydrogel system, as a desirable wound dressing, provides a new platform for promising melanoma therapy and skin regeneration.

Vascular endothelial S1pr1 ameliorates adverse cardiac remodelling via stimulating reparative macrophage proliferation after myocardial infarction

Cardiovascular Research · 2020 · 60 citations

• Medicine
• Cardiology
• Internal medicine

AIMS: Endothelial cell (EC) homoeostasis plays an important role in normal physiological cardiac functions, and its dysfunction significantly influences pathological cardiac remodelling after myocardial infarction (MI). It has been shown that the sphingosine 1-phosphate receptor 1 (S1pr1) was highly expressed in ECs and played an important role in maintaining endothelial functions. We thus hypothesized that the endothelial S1pr1 might be involved in post-MI cardiac remodelling. METHODS AND RESULTS: Our study showed that the specific loss of endothelial S1pr1 exacerbated post-MI cardiac remodelling and worsened cardiac dysfunction. We found that the loss of endothelial S1pr1 significantly reduced Ly6clow macrophage accumulation, which is critical for the resolution of inflammation and cardiac healing following MI. The reduced reparative macrophages in post-MI myocardium contributed to the detrimental effects of endothelial S1pr1 deficiency on post-MI cardiac remodelling. Further investigations showed that the loss of endothelial S1pr1-reduced Ly6clow macrophage proliferation, while the pharmacological activation of S1pr1-enhanced Ly6clow macrophage proliferation, thereby ameliorated cardiac remodelling after MI. A mechanism study showed that S1P/S1pr1 activated the ERK signalling pathway and enhanced colony-stimulating factor 1 (CSF1) expression, which promoted Ly6clow macrophage proliferation in a cell-contact manner. The blockade of CSF1 signalling reversed the enhancing effect of S1pr1 activation on Ly6clow macrophage proliferation and worsened post-MI cardiac remodelling. CONCLUSION: This study reveals that cardiac microvascular endothelium promotes reparative macrophage proliferation in injured hearts via the S1P/S1PR1/ERK/CSF1 pathway and thus ameliorates post-MI adverse cardiac remodelling.