Association between body mass index and results of cryoballoon ablation in Korean patients with atrial fibrillation: an analysis from the Korean Heart Rhythm Society Cryoablation registry.

AIMS: Pulmonary vein isolation using cryoablation is effective and safe in patients with atrial fibrillation (AF). Although both obesity and underweight are associated with a higher risk for incident AF, there is limited data on the efficacy and safety following cryoablation according to body mass index (BMI) especially in Asians. METHODS AND RESULTS: Using the Korean Heart Rhythm Society Cryoablation registry, a multicentre registry of 12 tertiary hospitals, we analysed AF recurrence and procedure-related complications after cryoablation by BMI (kg/m2) groups (BMI < 18.5, underweight, UW; 18.5-23, normal, NW; 23-25, overweight, OW; 25-30, obese Ⅰ, OⅠ; ≥30, obese Ⅱ, OⅡ). A total of 2648 patients were included (median age 62.0 years; 76.7% men; 55.6% non-paroxysmal AF). Patients were categorized by BMI groups: 0.9% UW, 18.7% NW, 24.8% OW, 46.1% OI, and 9.4% OII. Underweight patients were the oldest and had least percentage of non-paroxysmal AF (33.3%). During a median follow-up of 1.7 years, atrial arrhythmia recurred in 874 (33.0%) patients (incidence rate, 18.9 per 100 person-years). After multivariable adjustment, the risk of AF recurrence was higher in UW group compared with NW group (adjusted hazard ratio, 95% confidence interval; 2.55, 1.18-5.50, P = 0.02). Procedure-related complications occurred in 123 (4.7%) patients, and the risk was higher for UW patients (odds ratio, 95% confidence interval; 2.90, 0.94-8.99, P = 0.07), mainly due to transient phrenic nerve palsy. CONCLUSION: Underweight patients showed a higher risk of AF recurrence after cryoablation compared with NW patients. Also, careful attention is needed on the occurrence of phrenic nerve palsy in UW patients.

Increased risk of incident atrial fibrillation in young adults with mental disorders: A nationwide population-based study.

BACKGROUND: Mental disorders and cardiovascular diseases are closely related. However, a paucity of information on the risk of incident atrial fibrillation (AF) in patients with mental disorders exists. OBJECTIVE: We aimed to assess the association between mental disorders and the risk of AF, particularly in young adults. METHODS: Using the Korean National Health Insurance Database between 2009 and 2012, we identified adults aged 20-39 years without a history of AF and who have been diagnosed with mental disorders. Mental disorders were defined as having one of the following diagnoses: depression, insomnia, anxiety disorder, bipolar disorder, or schizophrenia. The primary outcome was new-onset AF during follow-up. RESULTS: A total of 6,576,582 subjects (mean age 30.9 ± 5.0 years; 3,919,339 [59.6%] men) were included. Among the total population, 10% had mental disorders. During the follow-up period, 8932 incident AF events occurred. Patients with mental disorders showed a higher AF incidence than did those without (25.4 per 100,000 person-years vs 17.7 per 100,000 person-years). After multivariable adjustment, mental disorders were associated with a significantly higher risk of AF (adjusted hazard ratio 1.526; 95% confidence interval 1.436-1.621). Patients with bipolar disorder or schizophrenia had a 2-fold higher risk of AF and those with depression, insomnia, and anxiety disorder had a 1.5- to 1.7-fold higher risk of AF than did those without mental disorders. CONCLUSION: Young adults diagnosed with mental disorders have a higher risk of incident AF. Awareness for AF in high-risk populations should thus be considered.

Impact of mental disorders on the risk of atrial fibrillation in patients with diabetes mellitus: a nationwide population-based study.

BACKGROUND: It is unclear whether mental disorders are an independent risk factor for atrial fibrillation (AF) in patients with diabetes. We aimed to investigate whether patients with diabetes who have mental disorders have an increased risk for AF. METHODS: Using the Korea National Health Insurance Service database, we enrolled 2,512,690 patients diagnosed with diabetes without AF between 2009 and 2012. We assessed five mental disorders: depression, insomnia, anxiety, bipolar disorder, and schizophrenia. Newly diagnosed AF was identified during the follow-up period, and multivariate Cox regression analysis was performed. RESULTS: Among the 2,512,690 patients (mean age 57.2 ± 12.3 years; 60.1% men), 828,929 (33.0%) had mental disorders. Among the five mental disorders, anxiety (68.1%) was the most common, followed by insomnia (40.0%). During a median follow-up duration of 7.1 years, new-onset AF was diagnosed in 79,525 patients (4.66 per 1,000 person-years). Patients with diabetes who had mental disorders showed a higher risk for AF (adjusted hazard ratio [HR] 1.19; 95% confidence interval [CI] 1.17-1.21; p-value < 0.001). Depression, insomnia, and anxiety were significantly associated with higher risk for AF (adjusted HR [95% CI]: 1.15 [1.12-1.17], 1.15 [1.13-1.18], and 1.19 [1.67-1.21], respectively; all p-values < 0.001), whereas bipolar disorder and schizophrenia were not. CONCLUSIONS: Mental disorders, especially depression, insomnia, and anxiety, were associated with an increased risk for AF in patients with diabetes. Greater awareness with a prompt diagnosis of AF should be considered for patients with both DM and mental disorders.

Eltrombopag for Post-Transplant Poor Graft Function in East Asian Patients.

Poor graft function (PGF) is a serious, potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation. Eltrombopag has shown multilineage responses in patients with refractory severe aplastic anemia, supporting the idea that it may improve cytopenia in patients with PGF. This retrospective, single center analysis included 8 Korean patients receiving eltrombopag for PGF. Median interval between transplant and eltrombopag treatment was 73 days, and the median duration treatment was 3.5 weeks. With median maximum daily dose of 50 mg, the time to best response was 93 days. Median hemoglobin increased from 8.2 g/dL to 10.9 g/dL, platelet from 18.5 × 109/L to 54 × 109/L, and absolute neutrophil count from 1.25 × 109/L to 3.32 × 109/L. In conclusion, eltrombopag is a good option for PGF in Korean patients, even at a lower dose compared to western patients.

Melittin-loaded Iron Oxide Nanoparticles Prevent Intracranial Arterial Dolichoectasia Development through Inhibition of Macrophage-mediated Inflammation.

Rationale: In intracranial arterial dolichoectasia (IADE) development, the feedback loop between inflammatory cytokines and macrophages involves TNF-α and NF-κB signaling pathways and leads to subsequent MMP-9 activation and extracellular matrix (ECM) degeneration. In this proof-of-concept study, melittin-loaded L-arginine-coated iron oxide nanoparticle (MeLioN) was proposed as the protective measure of IADE formation for this macrophage-mediated inflammation and ECM degeneration. Methods: IADE was created in 8-week-old C57BL/6J male mice by inducing hypertension and elastase injection into a basal cistern. Melittin was loaded on the surface of ION as a core-shell structure (hydrodynamic size, 202.4 nm; polydispersity index, 0.158). Treatment of MeLioN (2.5 mg/kg, five doses) started after the IADE induction, and the brain was harvested in the third week. In the healthy control, disease control, and MeLioN-treated group, the morphologic changes of the cerebral arterial wall were measured by diameter, thickness, and ECM composition. The expression level of MMP-9, CD68, MCP-1, TNF-α, and NF-κB was assessed from immunohistochemistry, polymerase chain reaction, and Western blot assay. Results: MeLioN prevented morphologic changes of cerebral arterial wall related to IADE formation by restoring ECM alterations and suppressing MMP-9 expression. MeLioN inhibited MCP-1 expression and reduced CD68-positive macrophage recruitments into cerebral arterial walls. MeLioN blocked TNF-α activation and NF-κB signaling pathway. In the Sylvian cistern, co-localization was found between the CD68-positive macrophage infiltrations and the MeLioN distributions detected on Prussian Blue and T2* gradient-echo MRI, suggesting the role of macrophage harboring MeLioN. Conclusions: The macrophage infiltration into the arterial wall plays a critical role in the MMP-9 secretion. MeLioN, designed for ION-mediated melittin delivery, effectively prevents IADE formation by suppressing macrophage-mediated inflammations and MMP activity. MeLioN can be a promising strategy preventing IADE development in high-risk populations.

Crystal structure of filamentous aggregates of human DJ-1 formed in an inorganic phosphate-dependent manner.

Mutations in the DJ-1 gene have been implicated in the autosomal recessive early onset parkinsonism. DJ-1 is a soluble dimeric protein with critical roles in response to oxidative stress and in neuronal maintenance. However, several lines of evidence suggest the existence of a nonfunctional aggregated form of DJ-1 in the brain of patients with some neurodegenerative diseases. Here, we show that inorganic phosphate, an important anion that exhibits elevated levels in patients with Parkinson disease, transforms DJ-1 into filamentous aggregates. According to the 2.4-A crystal structure, DJ-1 dimers are linearly stacked through P(i)-mediated interactions to form protofilaments, which are then bundled into a filamentous assembly.