Cryoballoon ablation of persistent atrial fibrillation for de novo pulmonary vein isolation: a single-center follow-up study.

BACKGROUND: Pulmonary vein isolation (PVI) alone for persistent atrial fibrillation (PersAF) remains controversial. The characteristics of cryoballoon ablation (CBA) to treat PersAF and the blanking period recurrence are underreported. METHODS: This study retrospectively analyzed patients with PersAF undergoing second-generation CBA for de novo PVI. The post-procedural efficacy and survival analysis were compared between patients with different PersAF durations. The multivariate Cox regression analysis was used to detect the risk factors for recurrence. Early and long-term recurrence were analyzed relative to each other. RESULTS: A total of 329 patients were enrolled, with a median PersAF duration of 4.0 months (interquartile range: 2.0-12.0 months); 257 patients (78.1%) were male. Kaplan-Meier analysis of freedom from atrial fibrillation recurrence at 12, 24, and 30 months showed 71.0%, 58.5%, and 54.9%, respectively. Early PersAF had a relatively favorable survival rate and a narrow P-wave duration of restoring sinus rhythm compared with that of PersAF lasting more than three months (P < 0.05). The multivariate Cox regression analysis revealed that PersAF duration and left atrial anteroposterior diameter ≥ 42 mm were the risk factors for atrial fibrillation recurrence after CBA [hazard ratio (HR) = 1.89, 95% CI: 1.01-1.4, P = 0.042; HR = 3.6, 95% CI: 2.4-5.4, P < 0.001, respectively]. The blanking period recurrence predicted the long-term recurrence (P < 0.0001). CONCLUSIONS: CBA of PersAF had safety and efficacy to reach de novo PVI. The PersAF duration and left atrial size were risk factors for atrial fibrillation recurrence after CBA. Blanking period recurrence was associated with long-term recurrence.

Design of Polymeric Zwitterionic Solid Electrolytes with Superionic Lithium Transport.

Progress toward durable and energy-dense lithium-ion batteries has been hindered by instabilities at electrolyte-electrode interfaces, leading to poor cycling stability, and by safety concerns associated with energy-dense lithium metal anodes. Solid polymeric electrolytes (SPEs) can help mitigate these issues; however, the SPE conductivity is limited by sluggish polymer segmental dynamics. We overcome this limitation via zwitterionic SPEs that self-assemble into superionically conductive domains, permitting decoupling of ion motion and polymer segmental rearrangement. Although crystalline domains are conventionally detrimental to ion conduction in SPEs, we demonstrate that semicrystalline polymer electrolytes with labile ion-ion interactions and tailored ion sizes exhibit excellent lithium conductivity (1.6 mS/cm) and selectivity (t + ≈ 0.6-0.8). This new design paradigm for SPEs allows for simultaneous optimization of previously orthogonal properties, including conductivity, Li selectivity, mechanics, and processability.

Risk of New-Onset Atrial Fibrillation Post-cavotricuspid Isthmus Ablation in Typical Atrial Flutter Without History of Atrial Fibrillation.

Aims: The aim was to describe the incidence of atrial fibrillation (AF) after cavotricuspid isthmus (CTI) ablation in patients with typical atrial flutter (AFL) without history of AF and to identify risk factors for new-onset AF after the procedure. Methods: A total of 191 patients with typical AFL undergoing successful CTI ablation were enrolled. Patients who had history of AF, structural heart disease, cardiac surgery, or ablation or who received antiarrhythmic drug after procedure were excluded. Clinical and electrophysiological data were collected. Results: There were 47 patients (24.6%) developing new AF during a follow-up of 3.3 ± 1.9 years after CTI ablation. Receiver operating characteristic (ROC) curves indicated that the cut-off values of left atrial diameter (LAD) and CHA2DS2-VASc score were 42 mm and 2, with area under the curve of 0.781 and 0.550, respectively. The multivariable Cox regression analysis revealed that obstructive sleep apnea (OSA) [hazard ratio (HR) 3.734, 95% confidence interval (CI) 1.470-9.484, P = 0.006], advanced interatrial block (aIAB) (HR 2.034, 95% CI 1.017-4.067, P = 0.045), LAD > 42 mm (HR 2.710, 95% CI 1.478-4.969, P = 0.001), and CHA2DS2-VASc score > 2 (HR 2.123, 95% CI 1.118-4.034, P = 0.021) were independent risk factors of new-onset AF. Conclusion: A combination of OSA, aIAB, LAD > 42 mm, and CHA2DS2-VASc > 2 was a strongly high risk for new-onset AF after ablation for typical AFL, and it had significance in postablation management in clinical practice.

Safety and Efficacy Using the Second-Generation Cryoballoon in Patients With Atrial Fibrillation and a Common Ostium of Inferior Pulmonary Veins.

Background: Common ostium of inferior pulmonary veins (COIPV) is a kind of pulmonary vein variation. The safety and efficacy of COIPV isolation using the second-generation cryoballoon (CB) ablation remain unknown. Methods: A total of 10 patients with COIPV from a consecutive series of 1,751 patients with atrial fibrillation (AF) were included. Pulmonary vein isolation (PVI) was performed using the second-generation CB. Results: The prevalence of a COIPV was 0.57% in this study. PVI was achieved in all pulmonary veins (PVs) without the need for a touch-up. A segmental freeze strategy was applied for each inferior PV, respectively. The mean number of freeze cycles of inferior PVs was 1.4 ± 0.5 for the left inferior pulmonary vein (LIPV), and 2.0 ± 0.9 for the right inferior pulmonary vein (RIPV). Pulmonary vein potential (PVP) of RIPV could not be monitored in real-time in three cases. Eight of 10 patients (80%) were free from atrial arrhythmias without the use of antiarrhythmic drugs during a follow-up period of 23.6 ± 12.9 months. No procedure-related complications occurred in any of the 10 patients. Conclusions: Common ostium of inferior pulmonary veins is a rare but challenging PV variant. PVI with this unusual anatomic variation using the second-generation 28-mm CB is effective and safe.

Novel Clue to Locate Conduction Gaps in the Pulmonary Vein Isolation Ablation Line.

Background: Several methods have been reported for locating the conduction gap (CG) in the pulmonary vein isolation (PVI) ablation line. However, the value of the interval between far-field atrial potential (FFP) and pulmonary vein potential (PVP) remains unknown. Methods: Consecutive patients with a CG during observation on the table after PVI were included. The PVP, FFP, and the CG location were evaluated to develop a novel algorithm to identify the CG location in the left superior pulmonary vein. The performance of this novel algorithm was prospectively tested in a validation cohort of consecutive patients undergoing repeat PVI ablation. Results: A total of 116 patients with atrial fibrillation (AF) were recruited, 56 of whom formed the validation cohort. The interval between FFP and PVP of the left superior pulmonary vein was associated with the CG location, and an interval <5 ms predicted the presence of CG in the upper portion of the ostium with a sensitivity of 92.9% and a specificity of 96.9%. In the prospective evaluation, the interval was able to correctly predict the site of CG in 89.6% of cases. Conclusions: The interval between FFP and PVP is a novel and accurate index that can be used to predict the CG location in the left superior pulmonary vein. An far-field atrial potential and pulmonary vein potential (FFP-PVP) interval value of ≥5 ms could be used to exclude a CG in the upper portion of the ostium in the majority of patients undergoing AF ablation.

Non-HDL-C Is More Stable Than LDL-C in Assessing the Percent Attainment of Non-fasting Lipid for Coronary Heart Disease Patients.

This study aimed to compare the percentage attainment of fasting and non-fasting LDL-C and non-HDL-C target levels in coronary heart disease (CHD) patients receiving short-term statin therapy. This study enrolled 397 inpatients with CHD. Of these, 197 patients took statins for <1 month (m) or did not take any statin before admission (CHD1 group), while 204 patients took statins for ≥1 m before admission (CHD2 group). Blood lipid levels were measured at 0, 2, and 4 h after a daily breakfast. Non-fasting LDL-C and non-HDL-C levels significantly decreased after a daily meal (P < 0.05). Both fasting and non-fasting LDL-C or non-HDL-C levels were significantly lower in the CHD2 group. The percentage attainment of LDL-C <1.4 mmol/L at 2 and 4 h after a daily breakfast was significantly higher than that during fasting (P < 0.05), but the percent attainment of non-fasting non-HDL-C <2.2 mmol/L was close to its fasting value (P > 0.05). Analysis of c-statistic showed that non-fasting cut-off points for LDL-C and non-HDL-C were 1.19 and 2.11 mmol/L, corresponding to their fasting goal levels of 1.4 and 2.2 mmol/L, respectively. When post-prandial LDL-C and non-HDL-C goal attainments were re-evaluated using non-fasting cut-off points, there were no significant differences in percentage attainment between fasting and non-fasting states. Non-HDL-C is more stable than LDL-C in assessing the percent attainment of non-fasting lipid for coronary heart disease patients. If we want to use LDL-C to assess the percent attainment of post-prandial blood lipids, we may need to determine a lower non-fasting cut-off point.

Comparison of Using Second-Generation Cryoballoon and Radiofrequency Catheter for Atrial Fibrillation Ablation in Patients With the Common Ostium of Inferior Pulmonary Veins.

Aims: To compare the procedural outcomes of cryoballoon ablation (CBA) and radiofrequency ablation (RFA) in atrial fibrillation (AF) patients with the common ostium of inferior pulmonary veins (COIPV) and to explore the effect of COIPV on CBA performance through the assessment of anatomical factors. Methods: A total of 18 AF patients with COIPV were included. Pulmonary vein isolation (PVI) was performed with second-generation CBA or RFA. The anatomical characteristics of COIPV and procedural outcomes were collected. Results: The prevalence of COIPV was 0.82% in the enrolled population. PVI was achieved in all pulmonary veins (PVs) without any complications. The "tricircle" strategy was applied for RFA, and the segmental freeze strategy was performed for CBA. Compared with RFA, CBA had shorter procedural time (median: 53.0 vs. 78.0 min, p < 0.001) and longer fluoroscopy time (median: 13.5 vs. 6.0 min, p < 0.001). Higher ovality index of the ostium was seen in patients with ≥4 freezes in inferior PVs [IPVs; 0.95 (0.78-1.05) vs. 0.49 (0.21-0.83), p = 0.047]. During a median of 23.5 months of follow-up, the atrial arrhythmias-free survival after the procedure was comparable between CBA and RFA (p = 0.729). Conclusion: The second-generation CBA is an efficient and safe alternative for RFA in AF patients with COIPV. Anatomical characteristics of COIPV bring the challenge to the procedure performance of RFA and CBA.

Pd-Catalyzed γ-C(sp3)-H Fluorination of Free Amines.

The first example of free amine γ-C(sp3)-H fluorination is realized using 2-hydroxynicotinaldehyde as the transient directing group. A wide range of cyclohexyl and linear aliphatic amines could be fluorinated selectively at the γ-methyl and methylene positions. Electron withdrawing 3,5-disubstituted pyridone ligands were identified to facilitate this reaction. Computational studies suggest that the turnover determining step is likely the oxidative addition step for methylene fluorination, while it is likely the C-H activation step for methyl fluorination. The explicit participation of Ag results in a lower energetic span for methylene fluorination and a higher energetic span for methyl fluorination, which is consistent with the experimental observation that the addition of silver salt is desirable for methylene but not for methyl fluorination. Kinetic studies on methyl fluorination suggest that the substrate and PdL are involved in the rate-determining step, indicating that the C-H activation step may be partially rate-determining. Importantly, an energetically preferred pathway has identified an interesting pyridone-assisted bimetallic transition state for the oxidative addition step in methylene fluorination, thus uncovering a potential new role of the pyridone ligand.

Electrical isolation of the superior vena cava using second-generation cryoballoon in patients with atrial fibrillation.

BACKGROUND: The safety and efficacy of superior vena cava (SVC) isolation using second-generation cryoballoon (CB) ablation remain unknown. METHODS: A total of 26 (3.2%) patients with SVC-related paroxysmal atrial fibrillation (AF) from a consecutive series of 806 patients who underwent second-generation CB were included. Pulmonary vein isolation was initially achieved by CB ablation. If the SVC trigger was determined, the electrical isolation of SVC isolation was performed using the second-generation CB. RESULTS: Real-time SVC potential was observed in all patients. Isolation of the SVC was successfully accomplished in 21 (80.8%) patients. The mean number of freeze cycles in each patient was 2.1 ± 1.1. The mean time to isolation and ablation duration were 22.5 ± 14.2 seconds and 94.5 ± 22.3 seconds, respectively. A transient phrenic nerve (PN) injury was observed in five patients (19.2%). There were two patients (7.7%) experienced reversible sinus node injury during the first application. During a mean follow-up period of 13.2 ± 5.8 months, four patients (15.4%) had atrial arrhythmia recurrences. CONCLUSION: Isolation of SVC using the second-generation 28-mm CB is feasible when SVC driver during AF is identified. Vigilant monitoring of PN function during CB ablation of SVC is needed to avoid PN injury.

Transient Directing Group Enabled Pd-catalyzed γ-C(sp3)-H Oxygenation of Alkyl Amines.

We report a general protocol for γ-C(sp3)-H acyloxylation and alkoxylation of free amines using 2-hydroxynicotinaldehyde as the transient directing group. In the presence of an electrophilic fluorinating bystanding oxidant and acetic acid, a wide range of aliphatic amines could be oxygenated selectively at the γ-methyl positions. A vast variety of aryl, heteroaryl, and aliphatic acids could also be successfully coupled under this C-O bond formation reaction to afford amine containing esters. Switching the nucleophile from acids to alcohols enables alkoxylation of free amines. Importantly, natural products and drug molecules such as ibuprofen, isozepac, fenbufen, and lithocholic acid are all compatible coupling partners. Notably, synthesis of these mono-protected amino alcohols from free amino alcohols using conventional selective protection are not always feasible.

Determination of optimal cut-off points after a high-fat meal corresponding to fasting elevations of triglyceride and remnant cholesterol in Chinese subjects.

BACKGROUND: Postprandial high triglyceride (HTG), marking elevated level of remnant cholesterol (RC), is an independent risk factor of coronary heart disease (CHD). The postprandial cut-off points for HTG and high RC (HRC) after a daily meal are recommended as 2.0 mmol/L and 0.9 mmol/L, respectively, by the European Atherosclerosis Society (EAS), while those after a high-fat meal in Chinese subjects were not explored. METHODS: Ninety subjects, including 60 CHD patients (CHD group) and 30 non-CHD controls (CON group), were enrolled in this study. Serum levels of blood lipids, including calculated RC, were monitored at 0, 2, 4 and 6 h after a high-fat meal with 800 kcal and 50 g fat. Analysis of c-statistic was used to determine the cut-off points for postprandial HTG and HRC. RESULTS: Postprandial levels of triglyceride (TG) and RC significantly increased and peaked at 4 h after a high-fat meal in two groups, although those in CHD group were significantly higher (P < 0.05). The optimal cut-off point to predict HTG at 4 h corresponding to fasting TG ≥ 1.7 mmol/L was 3.12 mmol/L, and that to predict HRC at 4 h corresponding to fasting RC ≥ 0.8 mmol/L was 1.36 mmol/L. According to the new cut-off points, the omissive diagnosis rates of postprandial HTG and HRC decreased obviously. CONCLUSION: The cut-off points of postprandial HTG and HRC in Chinese subjects after a high-fat meal were higher than those after a daily meal recommended by the EAS, indicating that specific cut-off points should be determined after a certain high-fat meal.

Comparison of non-fasting LDL-C levels calculated by Friedewald formula with those directly measured in Chinese patients with coronary heart disease after a daily breakfast.

BACKGROUND: LDL-C level can be measured by direct methods (LDL-CM) or calculated by Friedewald formula (LDL-CC). The aim of this study was to investigate the difference between LDL-CM and LDL-CC after a daily breakfast in Chinese patients with coronary heart disease (CHD). METHODS: Three hundred and three inpatients, including 203 CHD patients (CHD group) and 100 non-CHD controls (CON group), were enrolled in this study. Serum levels of blood lipid parameters, including LDL-CC and LDL-CM, at 0, 2 and 4 h (h) were monitored after a daily breakfast in all subjects. RESULTS: LDL-CM was significantly higher than LDL-CC in fasting state in each group and at 4 h postprandially in CHD group (P < .05). Postprandial LDL-CM and LDL-CC significantly decreased in each group (P < .05). Postprandial decline in LDL-CM was significantly greater than that of LDL-CC (P < .05). For CHD patients taking statins for ≥1 month before admission, non-fasting percent attainment of LDL-CM or LDL-CC was significantly higher than its fasting value, especially at 4 h (P < .05). The percent deviation of LDL-CM from 1.8 mmol/L at 4 h was significantly different from its fasting value. However, there was no significant difference in percent deviation of LDL-CC from 1.8 mmol/L between fasting and non-fasting states. CONCLUSIONS: It indicated that the clinical monitoring of non-fasting LDL-C level in CHD patients could be relatively complex, and the judgement may depend not only on the method to acquire LDL-C level, but also on the evaluation method.

Changes in non-fasting concentrations of blood lipids after a daily Chinese breakfast in overweight subjects without fasting hypertriglyceridemia.

BACKGROUND: Overweight is always accompanied by hypertriglyceridemia (HTG), but the change in non-fasting triglyceride (TG) concentration in overweight subjects without postprandial hypertriglyceridemia was unknown. METHODS: Concentrations of serum lipids were measured at 2 and 4 h in matched overweight (OW group, n = 54) and control subjects (CON group, n = 55) after a daily meal. Concentrations of remnant cholesterol and non-HDL cholesterol were calculated according to the formulas. The diagnostic criteria for non-fasting HTG were based on 2 different consensus statement. ROC curve was used to determine the pointcut of postprandial HTG. RESULTS: OW group had higher fasting concentrations of RC and non-HDL-C than CON group. Non-fasting concentrations of triglyceride and RC significantly increased in 2 groups while were higher in OW group (p < .05). The proportion of non-fasting HTG increased after a daily meal in OW group was significantly higher than the percentage of fasting HTG (p < .05). There was a significant correlation between the postprandial concentrations of TG and RC. CONCLUSIONS: Overweight subjects were more likely to develop non-fasting hypertriglyceridemia and higher concentrations of RC and non-HDL-C. Additionally, 2.0 mmol/l at 4 h after breakfast could be a pointcut value to detect changes in lipid profile of Chinese overweight people.

Overcoming the Limitations of γ- and δ-C-H Arylation of Amines through Ligand Development.

L,X-Type transient directing groups (TDGs) based on a reversible imine linkage have emerged as broadly useful tools for C-H activation of ketones and free amines. However, competitive binding interactions among multiple reaction components (TDG itself, substrate, and substrate-TDG adduct) with the palladium catalyst often lead to the formation of multiple unreactive complexes, rendering ligand development extremely challenging. Herein, we report the finding of versatile 2-pyridone ligands that addresses these problems and significantly improves the γ-methylene arylation of alkyl amines, extending the coupling partners to a wide range of medicinally important heteroaryl iodides and even previously unreactive heteroaryl bromides. The combination of an appropriate transient directing group and pyridone ligand has also enabled the δ-arylation of alkyl amines. Notably, our transient directing group design reveals the importance of matching the size of the Pd-chelation with different transient directing groups and the size of palladacycles generated from γ- and δ-C-H bonds: TDGs that coordinate with Pd(II) to form a six-membered chelate are selective toward γ-C-H bonds, whereas TDGs that coordinate with Pd(II) via a five-membered chelate tend to activate δ-C-H bonds. These findings provide an avenue for developing protecting group free and selective C-H functionalization using the transient directing group strategy.

Pd-Catalyzed Remote Meta-C-H Functionalization of Phenylacetic Acids Using a Pyridine Template.

An effective pyridine based U-shaped template has been developed to enable a diverse range of meta-C-H functionalizations of phenylacetic acid scaffolds. This new template has extended the reaction scope to cross-coupling with ArBF3K as well as iodination using 1,3-diiodo-5,5-dimethylhydantoin as the iodination reagent.

Potential Medication Treatment According to Pathological Mechanisms in Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is a vascular disease with high mortality. Because of the lack of effective medications to stop or reverse the progression of AAA, surgical operation has become the most predominant recommendation of treatment for patients. There are many potential mechanisms, including inflammation, smooth muscle cell apoptosis, extracellular matrix degradation, oxidative stress, and so on, involving in AAA pathogenesis. According to those mechanisms, some potential therapeutic drugs have been proposed and tested in animal models and even in clinical trials. This review focuses on recent advances in both pathogenic mechanisms and potential pharmacologic therapies of AAA.

Identification of monodentate oxazoline as a ligand for copper-promoted ortho-C-H hydroxylation and amination.

The use of a weakly coordinating monodentate directing group for copper mediated ortho-hydroxylation and amination reactions allows for the identification of an external oxazoline ligand as a promoter.

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Low-altitude unmanned aerial vehicles (UAV) remote sensing system overcomes the deficiencies of space and aerial remote sensing system in resolution, revisit period, cloud cover and cost, which provides a novel method for ecological research on mesoscale. This study introduced the composition of UAV remote sensing system, reviewed its applications in species, population, community and ecosystem ecology research. Challenges and opportunities of UAV ecology were identified to direct future research. The promising research area of UAV ecology includes the establishment of species morphology and spectral characteristic data base, species automatic identification, the revelation of relationship between spectral index and plant physiological processes, three-dimension monitoring of ecosystem, and the integration of remote sensing data from multi resources and multi scales. With the development of UAV platform, data transformation and sensors, UAV remote sensing technology will have wide application in ecology research.

Pd-Catalyzed γ-C(sp3)-H Arylation of Free Amines Using a Transient Directing Group.

Pd(II)-catalyzed γ-C(sp3)-H arylation of primary amines is realized by using 2-hydroxynicotinaldehyde as a catalytic transient directing group. Importantly, the catalyst and the directing group loading can be lowered to 2% and 4% respectively, thus demonstrating high efficiency of this newly designed transient directing group. Heterocyclic aryl iodides are also compatible with this reaction. Furthermore, swift synthesis of 1,2,3,4-tetrahydronaphthyridine derivatives is accomplished using this reaction.

Ligand-accelerated enantioselective methylene C(sp3)-H bond activation.

Effective differentiation of prochiral carbon-hydrogen (C-H) bonds on a single methylene carbon via asymmetric metal insertion remains a challenge. Here, we report the discovery of chiral acetyl-protected aminoethyl quinoline ligands that enable asymmetric palladium insertion into prochiral C-H bonds on a single methylene carbon center. We apply these palladium complexes to catalytic enantioselective functionalization of ß-methylene C-H bonds in aliphatic amides. Using bidentate ligands to accelerate C-H activation of otherwise unreactive monodentate substrates is crucial for outcompeting the background reaction driven by substrate-directed cyclopalladation, thereby avoiding erosion of enantioselectivity. The potential of ligand acceleration in C-H activation is also demonstrated by enantioselective ß-C-H arylation of simple carboxylic acids without installing directing groups.