Long-term outcomes of left atrial appendage closure with or without concomitant pulmonary vein isolation:a propensity score matching analysis based on CLACBAC study.

BACKGROUND: The combined procedure of left atrial appendage closure (LAAC) with concomitant pulmonary vein isolation (PVI) has demonstrated its efficacy and safety. However, there is still a lack of comparative investigations regarding the long-term benefits of the combined procedure when compared to LAAC alone. Our study aims to assess the long-term outcomes of combined procedure of LAAC with concomitant PVI in comparison with a propensity matched LAAC alone group. METHODS: Propensity score matching (PSM) was employed to rectify covariate imbalances, resulting in the inclusion of 153 comparable patients from the initial cohort of 333 non-valvular atrial fibrillation (AF) patients. Clinical outcomes, encompassing thrombotic events, major cardiocerebrovascular adverse events (MACCE), re-hospitalization due to cardiovascular disease (CVD), and atrial tachycardia (AT), were juxtaposed between the two groups. Bleeding events and peri-device complications, such as residual flow, device-related thrombus, and device replacement, were also compared. Additionally, a patients group underwent PVI alone was included for comparing AF recurrence rates between the PVI alone group and the combined group. RESULTS: Following PSM, 153 patients (mean age 70.3 ± 8.9, 62.7% men) were included, with 102 undergoing the combined procedure and 51 undergoing LAAC alone. No significant differences were found in baseline characteristics between the two groups. The mean follow-up time was 37.6 ± 7.9 months, and two patients were lost to follow-up in the combined procedure group. Thrombotic events were observed in 4 (7.8%) patients in the LAAC alone group and 4 (4.0%) in the combined group (Log-rank p = 0.301). The proportion of patients experiencing MACCE, re-hospitalization due to CVD, and AT between the two groups was comparable, as were bleeding events and peri-device complications. Among patients from the combined procedure group without AF recurrence, a significant difference was noted in prior-procedure left ventricular ejection fraction (LVEF) and LVEF at the 12th month after the procedure (57.2% ± 7.1% vs. 60.5% ± 6.5%, p = 0.002). CONCLUSION: The concomitant PVI and LAAC procedure did not increase procedure-related complications, nor did it confer significant benefits in preventing thrombotic events or reducing other cardiovascular events. However, the combined procedure improved heart function, suggesting potential long-term benefits.

Improved in situ analysis of lead isotopes in low-Pb melt inclusions using laser ablation-multi-collector-inductively coupled plasma-mass spectrometry.

RATIONALE: In situ Pb isotope analyses of tiny melt inclusions using laser ablation-multi-collector-inductively coupled plasma-mass spectrometry (LA-MC-ICP-MS) are crucial for exploring the origins of mafic lavas. However, quantitative use of this technique with low-Pb (<10 ppm) melt inclusions is difficult due to their low 204 Pb content and 204 Hg interference. METHODS: Pb isotopic ratios of various reference glasses and olivine-hosted melt inclusions were determined using LA-MC-ICP-MS. Multiple ion counters were used to simultaneously determine signal intensities of all Pb isotopes and 202 Hg. An Hg signal-removal smoothing device reduced its signal in the gas blank by >80%. Instrumental mass bias was corrected using the standard-sample bracketing method. RESULTS: With 24-90 µm diameter laser spots, 2-4 Hz repetition rates, and 2.5-4 J cm-2 energy fluence, the analytical precisions of 20x Pb/204 Pb ratios (x = 6, 7, 8) for standards BHVO-2G, ML3B-G, NIST 614, NKT-1G, T1-G, GOR132-G, and StHs6/80-G were <1.0% (2RSD) when 208 Pb signals >100 000 cps. The Wangjiadashan melt inclusions have 206 Pb/204 Pb = 17.14-18.44, 207 Pb/204 Pb = 15.28-15.66, and 208 Pb/204 Pb = 37.12-38.68. CONCLUSIONS: The described method improves the precision and accuracy of in situ Pb isotope analysis in low-Pb melt inclusions using LA-MC-ICP-MS. The Pb isotopic compositions of the Wangjiadashan melt inclusions indicate the coexistence of LoMu and EMII+young HIMU components in the mantle source of weakly alkaline basalts.

Evaluation of Patients with Angiographically-Confirmed Coronary Artery Disease to Investigate the Association Between Epicardial Fat Thickness and Atrial Fibrillation.

BACKGROUND Epicardial fat thickness (EFT) is increasingly recognized as an independent risk factor of the presence, severity, and recurrence of atrial fibrillation (AF). We investigated the associations between EFT and AF prevalence and identified its correlation with other risk factors. MATERIAL AND METHODS A total of 199 participants who underwent coronary angiography and had confirmed coronary artery disease (CAD) were enrolled in this study. The EFT was measured by echocardiography and the association of EFT with other AF risk factors was evaluated by multivariate logistic regression analysis. RESULTS The EFT was significantly higher in patients with comorbidity of AF and CAD than those with CAD alone (6.86±1.96 mm vs 5.91±1.71 mm, P<0.001). Logistic regression analysis indicated that EFT was a predictive factor of the occurrence of AF in CAD, after adjusting for body mass index (BMI), systolic blood pressure (SBP), left circumflex artery (LCX) stenosis, LA diameter, B-type natriuretic peptide (BNP), creatinine (Cr), and blood urea nitrogen (BUN). LA diameter, SBP, and LCX stenosis are also independent risk factors for CAD complicated by AF. Correlation analysis revealed significant positive linear correlations between EFT and BMI (P<0.01), EFT, and LA diameter (P<0.05), as well as positive correlations between LA diameter and BNP, Cr, or BUN. CONCLUSIONS Epicardial fat thickness is a strong predictor for AF prevalence in patients with CAD, independent of other AF risk factors such as LA diameter, BMI, and SBP, while LA diameter, SBP, and LCX stenosis are also independent AF risk factors for CAD.

Higher FT4 level within the normal range predicts the outcome of cryoballoon ablation in paroxysmal atrial fibrillation patients without structural heart disease.

BACKGROUND: Accumulated evidence has indicated that a high-normal FT4 level is an independent risk factor for the clinical progression of AF. However, the association between elevated FT4 concentration within the normal range and AF recurrence after cryoballoon ablation in China is unknown. METHODS: This retrospective and observational study included 453 AF patients who underwent cryoballoon ablation from January 2016 to August 2018. Patients were classified into quartiles based on preprocedural serum FT4 concentration. The clinical characteristics of the patients and the long-term rate of AF recurrence after ablation were assessed. RESULTS: After a mean follow-up period of 17.4 ± 9.0 months, 91 (20.1%) patients suffered from AF recurrence. The AF recurrence rate by FT4 quartile was 17.7%, 19.0%, 21.4%, and 22.3% for participants with FT4 in quartile 1, 2, 3, and 4, respectively (p < .001). On multivariate Cox regression, FT4 concentration (HR: 1.187, 95% CI: 1.093-1.290, p < .001) and left atrial diameter (HR: 1.052, 95% CI: 1.014-1.092, p = .007) were significant predictors of AF recurrence. When stratifying for AF type, the rate of postoperative recurrence was independently increased as FT4 concentration increased in paroxysmal AF, but not in persistent AF (p < .001 in paroxysmal AF and p = .977 in persistent AF). CONCLUSION: Higher FT4 level within the normal range predicted the outcome of cryoballoon ablation in Chinese paroxysmal AF patients without structural heart disease.

Recurrent atrial fibrillation after initial cryoballoon ablation: New perspectives for intensive ablation in right superior pulmonary vein ostium for atrial fibrillation.

A significant proportion of patients with recurrent atrial fibrillation (AF) require repeat radiofrequency (RF) ablation after cryoballoon (CB) ablation. However, little is known about the pulmonary vein (PV) potential reconnection to left atrium and localization of gaps in the initial lesion sets following cryoablation in patients with recurrent AF. The data of 29 consecutive patients with repeat RF ablation for recurrent AF were analyzed. During the second ablation procedures, PV foci of AF were explored in 116 PVs by the CARTO system. All patients had complete PV isolation from initial cryoablation procedure. The fluoroscopy duration, mean cryoablation time and mean cryoablation frequency were lowest for the right superior pulmonary vein (RSPV) (58.69 ± 9.18 s, 185.10 ± 49.25 s and 1.07 ± 0.26; p = 0.024, p = 0.042 and p = 0.032). A significantly higher incidence of conduction gaps per patient was found for the RSPVs compared to the other PVs (p < 0.05 or p < 0.01). For RSPVs, it seemed that gaps were predominantly located at the anterior segment (22 gaps) and inferior segment (22 gaps). RSPV reconnection was independently related to a lower risk of major adverse events after the second ablation during follow up in the study patients (HR 0.275, 95%CI 0.078-0.967, p = 0.044). AF recurrence in patients after cryoablation is significantly associated with conduction gaps in the anterior and inferior segments of RSPVs. Various ablation strategies of close touch of CB on anterior and inferior segments of RSPV ostium, more freezing time and frequency for RSPV may help achieving durable PV isolation during follow up.

Acute left atrial ridge lesion after cryoballoon ablation: How does this affect left atrial appendage closure combined procedure?

BACKGROUND: Acute left atrial ridge (LAR) lesions have been observed following atrial fibrillation (AF) ablation. However, LAR lesions had not yet been quantitatively evaluated and their influence on procedure combining cryoballoon (CB) ablation with left atrial appendage closure (LAAC) remained to be explored. METHODS: The profile of LAR lesions was measured by transesophageal echocardiography (TEE) in 117 consecutive nonvalvular AF patients, who underwent the combined procedure of CB ablation and LAAC. We thoroughly investigated how LAR lesions correlated with baseline variables and clinical outcomes. RESULTS: A total of 95 out of 96 available TEE images presented prominent acute LAR lesions. In terms of dimensions, there was a greater change in width (Δwidth = 3.6 ± 2.3 mm) than the thickness (Δthickness = 2.6 ± 3.5 mm), and the outer ostium was narrowed (Δouter ostium diameter = -3.4 ± 4.0 mm), while the inner ostium remained unchanged. A higher nadir temperature when freezing the left superior pulmonary vein (LSPV) led to an LAR lesion with a two times greater width (adjusted odds ratio = 1.16; 95% confidence interval, 1.02-1.31). In the evaluation of LAAC outcomes, four patients implanted with Watchman devices had minimal residual flow at the inferior border, while two implanted with LAmbre devices developed residual flow at the LAR side. Clinical outcomes were similar between groups divided by lesion size. CONCLUSION: Acute LAR lesions frequently occurred following the CB ablation combined procedure, and lesion width positively correlates with LSPV nadir temperature. The presence of these lesions affects the measurement of pacifier devices but has little impact on that of occluder devices.

Efficacy and safety of cryoballoon ablation for Chinese patients over 75 years old: A comparison with a younger cohort.

INTRODUCTION: Cryoballoon ablation (CBA) results in satisfactory outcomes for drug-resistant atrial fibrillation (AF) patients. However, the efficacy and safety of CBA have not yet been tested in the Chinese elderly population. Therefore, this study compared the recurrence of AF and complications of CBA in patients ≥75 years and <75 years. METHODS: A total of 677 patients (<75 years, n = 550; ≥ 75 years, n = 127) with paroxysmal (n = 603) or persistent (n = 74) non-valvular drug-resistant AF were included. The efficacy was assessed by the recurrence of AF, and the safety was evaluated by peri- and post-procedural complications. RESULTS: The CHA2DS2-VASc (2.6 ± 1.7 vs 4.8 ± 1.6, P < .01) and HAS-BLED (1.8 ± 0.8 vs 2.0 ± 0.8, P = .01) scores were significantly higher in the elderly group. The instant pulmonary vein isolation success rate was comparable (99.11% younger vs 98.98% older, P = .99). After a mean follow-up time of 12.8 ± 9.6 months, the 1-year freedom from AF rate was 80.6% vs 85.8% in the older and younger groups, respectively, while the survival analysis showed a nonsignificant difference in the rate of freedom from AF (log-rank P = .46). Cox regression showed that age was not a predictive factor for AF recurrence and was not dichotomized (hazard ratio [HR] = 0.868, 95% confidence interval [CI] 0.509-1.481; P = .6046) or continuous (HR = 0.990, 95% CI, 0.968-1.012, P = .3642). Similar complications rates were observed, including stroke (1.0% younger vs 0.93% older, P = .95) and major hemorrhagic events (1.2% younger vs 0% elder, P = .25). CONCLUSIONS: The efficacy and safety profiles of CBA in patients older than 75 years are comparable with those in younger patients.

In situ determination of trace elements in melt inclusions using laser ablation inductively coupled plasma sector field mass spectrometry.

RATIONALE: In situ trace element analysis of melt inclusions by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) provides important geochemistry information. However, the precision and accuracy of this technique are affected by many factors, such as matrix effect, laser conditions, and calibration method. In addition, many previous LA-ICP-MS studies ablated entire melt inclusions along with their host minerals and obtained trace element composition by deconvoluting the mixed ablation signal, which may induce much uncertainty. METHODS: A 193 nm ArF laser ablation system combined with inductively coupled plasma sector field mass spectrometry (ICP-SF-MS) was used to investigate matrix effect, laser conditions, choice of external calibration standards, and data reduction strategy for in situ analysis of 36 major and trace elements in six common silicate reference glasses. The validity of the protocol presented here was demonstrated by measuring trace elements in olivine-hosted melt inclusions. Instead of ablating entire melt inclusions along with their host minerals, melt inclusions were polished to the surface to avoid laser ablating the mineral host. RESULTS: The calibration lines calculated from the calibration standards should cross the coordinate origin, especially for low-concentration elements (<10 ppm). As the laser crater size increased from 17 to 33 µm, the precision was improved from <20% to <8% (2RSD), and accuracy was improved from ±20% to better than ±10%. Most measured trace elements in Dali melt inclusions are consistent with those in their host rocks. For mobile elements (Ba, Sr, Pb), melt inclusions display much smaller variations than their host rocks. CONCLUSIONS: A simple but accurate approach for in situ analysis of trace elements in melt inclusions by LA-ICP-SF-MS has been established, which should greatly facilitate the wider application of in situ trace element geochemistry to melt inclusion studies.

Design, synthesis and biological evaluation of inhibitors of cathepsin K on dedifferentiated chondrocytes.

Selective proteinase inhibitors have demonstrated utility in the investigation of cartilage degeneration mechanisms and may have clinical use in the management of osteoarthritis. The cysteine protease cathepsin K (CatK) is an attractive target for arthritis therapy. Here we report the synthesis of two cathepsin K inhibitors (CKIs): racemic azanitrile derivatives CKI-E and CKI-F, which have better inhibition properties on CatK than the commercial inhibitor odanacatib (ODN). Their IC50 values and inhibition constants (Ki) have been determined in vitro. Inhibitors demonstrate differential selectivity for CatK over cathepsin B, L and S in vitro, with Ki amounting to 1.14 and 7.21 nM respectively. We analyzed the effect of these racemic inhibitors on viability in different cell types. The human osteoblast-like cell line MG63, MOVAS cells (a murine vascular smooth muscle cell line) or murine primary chondrocytes, were treated either with CKI-E or with CKI-F, which were not toxic at doses of up to 5 µM. Primary chondrocytes subjected to several passages were used as a model of phenotypic loss of articular chondrocytes, occurring in osteoarthritic cartilage. The efficiency of CKIs regarding CatK inhibition and their specificity over other proteases were validated in primary chondrocytes subjected to several passages. Racemic CKI-E and CKI-F at 0.1 and 1 µM significantly inhibited CatK activity in dedifferentiated chondrocytes, even better than the commercial CatK inhibitor ODN. The enzymatic activity of other proteases such as matrix metalloproteinases or aggrecanases were not affected. Taken together, these findings support the possibility to design CatK inhibitors for preventing cartilage degradation in different pathologies.

Strontium isotope measurement of basaltic glasses by laser ablation multiple collector inductively coupled plasma mass spectrometry based on a linear relationship between analytical bias and Rb/Sr ratios.

RATIONALE: In situ strontium (Sr) isotope analysis of geological samples by laser ablation multiple collector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) provides useful information about magma mixing, crustal contamination and crystal residence time. Without chemical separation, during Sr isotope analysis with laser ablation, many kinds of interference ions (such as Rb+ and Kr+ ) are on the Sr isotope spectrum. Most previous in situ Sr isotope studies only focused on Sr-enriched minerals (e.g. plagioclase, calcite). Here we established a simple method for in situ Sr isotope analysis of basaltic glass with Rb/Sr ratio less than 0.14 by LA-MC-ICP-MS. METHODS: Seven Faraday cups, on a Neptune Plus MC-ICP-MS instrument, were used to receive the signals on m/z 82, 83, 84, 85, 86, 87 and 88 simultaneously for the Sr isotope analysis of basaltic glass. The isobaric interference of 87 Rb was corrected by the peak stripping method. The instrumental mass fractionation of 87 Sr/86 Sr was corrected to 86 Sr/88 Sr = 0.1194 with an exponential law. Finally, the residual analytical biases of 87 Sr/86 Sr were corrected with a relationship between the deviation of 87 Sr/86 Sr from the reference values and the measured 87 Rb/86 Sr. The validity of the protocol present here was demonstrated by measuring the Sr isotopes of four basaltic glasses, a plagioclase crystal and a piece of modern coral. RESULTS: The measured 87 Sr/86 Sr ratios of all these samples agree within 100 ppm with the reference values. In addition, the Sr isotopes of olivine-hosted melt inclusions from the Emeishan large igneous province (LIP) were measured to show the application of our method to real geological samples. CONCLUSIONS: A simple but accurate approach for in situ Sr isotope measurement by LA-MC-ICP-MS has been established, which should greatly facilitate the wider application of in situ Sr isotope geochemistry, especially to volcanic rock studies.

[In Situ Infrared Spectroscopic Determination of Enzyme Activity].

A real-time infrared (IR) spectroscopy measurement is an effective means to obtain enzymatic information either in vitro or in living cells, as it can provide direct, continue test of biomacromolecule reactions. The principles of measurements are performed basing on the fact that the absorption bands in spectra of reactants and products are usually separated to each other and changed independently with time. Therefore, it is possible to measure the enzymatic efficiency at any reaction time according to the changes of characteristic band, from either reactant or product. That is, IR spectroscopy can be used to obtain intracellular structural information during the cells metabolic processes, as which can provide detailed and reliable scientific evidences. In this paper, we summarized the new developments of IR spectra in the in vitro enzymatic assay for several representative enzymes, as well the screening of enzyme inhibitors, which was further extended to the identical aspect by using living cells as detection model. Such important enzymatic examination closes to the physiological conditions without labeling, supplying structural information of the related biomolecules. The developing trends of IR spectra are discussed and the perspectives of it in the research area are also provided in this review.

Mechanisms of pathogenicity in the hypertrophic cardiomyopathy-associated TNNI3 c.235C > T variant.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is typically manifested as a hereditary disorder, with 30 %-60 % of cases linked to cardiac sarcomere gene mutations. Despite numerous identified TNNI3 mutations associated with HCM, their severity, prevalence, and disease progression vary. The link between TNNI3 variants and phenotypes remains largely unexplored. This study aims to elucidate the impact of the TNNI3 c.235C > T mutation on HCM through clinical research and cell experiments and to explore its mechanism in HCM development. METHODS: We screened an HCM family for pathogenic gene mutations using gene sequencing. The proband and family members were assessed through electrocardiography, echocardiography, and cardiac MRI, and a pedigree map was created for disease prediction analysis. Mutant plasmids were constructed with the TNNI3 c.235C > T mutation and transfected into the AC16 human cardiomyocyte cell line to investigate the mutation's effects. RESULTS: The TNNI3 c.235C > T mutation was identified as the disease-causing variant in the family. This mutation led to the upregulation of hypertrophy-associated genes ANP, BNP, and MYH7, increased cardiomyocyte size, and activation of the ERK signaling pathway. Further investigations revealed that the TNNI3 c.235C > T mutation impaired mitochondrial function, disrupted cardiomyocyte metabolism, and increased cellular autophagy and apoptosis. CONCLUSIONS: The TNNI3 c.235C > T gene mutation may be a pathogenic factor for HCM, showing heterogeneous features and clinical phenotypes. This mutation induces myocardial hypertrophy, activates the ERK signaling pathway, and exacerbates mitochondrial dysfunction, apoptosis, and autophagy in cardiomyocytes. These findings provide insights into the mechanism of HCM caused by gene mutations and may inform HCM treatment strategies.

Age and blood pressure stratified healthy vascular aging, organ damage and prognosis in the community-dwelling elderly: insights from the North Shanghai Study.

BACKGROUND: This study aimed to investigate the prognostic value of age and blood pressure stratified healthy vascular aging (HVA) defined in the North Shanghai Study (NSS), and illustrate its relationship with organ damage (OD). METHODS: This study enrolled 3590 community-dwelling elderly Chinese aged over 65 years and finally 3234 participants were included. 3230 individuals were included in the final analysis, with 4 participants lost to follow-up. NSS HVA was defined as low carotid-femoral pulse wave velocity (PWV) which had a higher cutoff value with advanced age and level of blood pressure. OD was thoroughly assessed and classified into vascular, cardiac and renal OD. Primary endpoints were major adverse cerebrocardiovascular events (MACCE) and all-cause mortality. RESULTS: Nine hundred seventy-eight participants out of 3234 participants (43.1%) were identified as having NSS HVA. The NSS HVA group exhibited a younger age, lower blood pressure levels, lower body mass index, and milder OD compared to the non-NSS HVA group. Over follow-up of 5.7 ± 1.8 years, 332 MACCE (1.82 per 100 person-year) and 212 all-cause deaths (1.14 per 100 person -year) occurred. NSS HVA was associated with a reduced risk of MACCE (HR [95% CI] = 0.585, 0.454-0.754) and all-cause death (HR [95%CI] = 0.608 [0.445, 0.832]), especially in those subgroups without clinical diagnosed cardiovascular disease (CVD) or diabetes mellitus but with at least one type of OD. Moreover, NSS HVA exhibited improved prognostic value for MACCE, all-cause death and CVD death compared to other definitions of HVA. CONCLUSIONS: Age and blood pressure stratified NSS HVA could serve as an improved indicator against serious adverse events in the community-dwelling elderly Chinese. TRIAL REGISTRATION: Prognosis in the Elderly Chinese: The Northern Shanghai Study (NSS), NCT02368938, https://clinicaltrials.gov/study/NCT02368938?cond=NCT02368938&rank=1 .

Prognosis of early-stage HFpEF in the community-dwelling elderly: The Northern Shanghai Study.

OBJECTIVE: Heart failure with preserved ejection fraction (HFpEF) is a growing concern among the elderly population, significantly impacting morbidity and mortality rates. This study aimed to screen and investigate the characteristics and prognosis of early-stage HFpEF in the elderly. METHODS: A total of 1789 community-dwelling individuals aged over 65 from northern Shanghai were enrolled. According to American Heart Association (AHA) guidelines, participants were classified into four groups: HFpEF stage 0, HFpEF stage A, HFpEF stage B and HFpEF stage C. Major endpoints included major adverse cardiovascular events (MACEs), all-cause death and cardiovascular death. RESULTS: After a mean follow-up period of 7.10 ± 1.27 years, 1623 elderly subjects were included [HFpEF stage 0 (10.3%), HFpEF stage A (16.3%), HFpEF stage B (60.6%) and HFpEF stage C (12.8%)]. Patients with HFpEF stage A, HFpEF stage B and HFpEF stage C exhibited more MACEs than those in HFpEF stage 0 (P < 0.01). Patients with HFpEF stage C had a significantly higher cardiovascular (P < 0.001) and all-cause death ratio (P < 0.01). With HFpEF stage 0 as a reference, the increases in MACEs were significantly associated with HFpEF stage A [hazard ratio (HR): 2.97, 95% confidence interval (CI) (1.13, 7.82), P < 0.05], HFpEF stage B [HR: 2.69, 95% CI (1.09, 6.64), P < 0.05] and HFpEF stage C [HR: 4.86, 95% CI (1.88, 12.59), P < 0.01] in the Cox regression analysis. Our finding remains unaltered in the sensitivity analysis, with no interaction for effectiveness. CONCLUSIONS: Compared with those with HFpEF stage 0, patients with HFpEF, whether in stage B or C, exhibit significantly higher cardiovascular and all-cause mortality in the elderly. This study underscores the importance of early-stage HFpEF screening, particularly in older, asymptomatic stage B individuals.

The presence of spontaneous echo contrast didn't increase the risk for left atrial appendage closure: A propensity score matching analysis based on the CLACBAC study.

Background: Left atrial appendage closure (LAAC) was effective in preventing thromboembolic events and stroke in patients with atrial fibrillation (AF). However, whether left atrial spontaneous echo contrast (LA-SEC) poses a higher risk for thromboembolism is contradictory. We aimed to investigate whether LA-SEC is a risk factor for thromboembolic events in patients who underwent LAAC. Methods: 258 consecutive patients who underwent successful LAAC were enrolled and divided according to the presence or absence of LA-SEC detected by transesophageal echocardiography (TEE). Propensity score matching (PSM) was used to eliminate covariate imbalances. Baseline characteristics, periprocedural details, and clinical outcomes were compared between LA-SEC and non-LA-SEC groups and PSM-matched groups. Results: Of the 258 patients enrolled, mean age was 71.8 ± 8.3 years and 59.3 % were male. LA-SEC group had a higher percentage of persistent AF and worse cardiac function. No significant difference in peri-procedure parameters was found. Through follow-up of 38.1 ± 10.7 months, the total incidence of thromboembolic events and stroke was 7.8 % and 6.6 %, respectively. Though the event-free survival rate of thromboembolic events (Log-Rank P = 0.042) and stroke (Log-Rank P = 0.010) was significantly lower in the LA-SEC group, multivariable COX regression analysis showed LA-SEC was not an independent predictor of thromboembolic events (Hazard ratio 2.073, 95 % Confidence interval 0.845-5.082, P = 0.111). Further survival analysis between PSM-matched groups with comparable baseline characteristics presented no significant difference in survival free from thromboembolic events (Log-Rank P = 0.616) and stroke (Log-Rank P = 0.312). Conclusion: Patients with LA-SEC had worse condition, while LA-SEC per se did not increase the incidence of thromboembolic events and stroke for patients who underwent LAAC.

Liquid Nitrogen Cryoballoon Ablation System for Paroxysmal Atrial Fibrillation: A Multicenter, Prospective, Single-Arm Clinical Trial.

Background: Cryoballoon ablation (CBA) has emerged as an effective treatment for atrial fibrillation (AF). Objectives: This study sought to assess the performance of a novel liquid nitrogen-driven CBA system and evaluate its safety and efficacy in the treatment of drug-resistant paroxysmal atrial fibrillation (PAF). Methods: This was a prospective multicenter single-arm clinical trial with 10 participating tertiary hospitals enrolling 176 patients with PAF. All participants received liquid nitrogen-driven CBA developed by the Cryofocus Medtech Company. Scheduled follow-up was performed before discharge and 3 months, 6 months, and 12 months after CBA. The primary endpoints were defined as 1) treatment success (freedom from antiarrhythmic drugs and atrial tachycardia at 12 months after CBA); and 2) immediate success rate of pulmonary vein isolation. The safety endpoint was the incidence of device- and procedure-related adverse events (AEs) and all-cause mortality. Results: A total of 172 participants were included, with an average age of 59.22 ± 9.25 years and 99 (57.56%) of them men. Immediate success rate was 97.67% (95% CI: 94.15%-99.36%) and 12-month treatment success rate was 82.56% (95% CI: 76.89%-88.23%), including a late recurrence rate of 13.61%. Incidences of device- and procedure-related AEs were 2.27% and 25.00%, respectively. Phrenic nerve palsy (PNP) occurred in 6 patients, of which 5 recovered during follow-up. Although the incidence of total severe AEs was 17.05%, including an all-cause mortality of 0.57%, only 1 case of permanent PNP was related to the CBA procedure. Conclusions: This premarketing prospective multicenter single-arm clinical trial demonstrated that the liquid nitrogen cryoablation system is safe and effective in the treatment of PAF.

Guiding atrial fibrillation ablation combined with left atrial appendage occlusion procedure by fluoroscopy with or without transesophageal echocardiography achieved comparable outcomes.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia and can be treated with catheter ablation (CA) combined with left atrial appendage occlusion (LAAO). The study is designed to compare the safety and efficacy of guiding the combined procedure by digital subtraction angiography (DSA) with or without transesophageal echocardiography (TEE). METHODS: From February 2019 to December 2020, 138 patients with nonvalvular AF who underwent CA combined with LAAO procedure were consecutively included, and two cohorts were built according to intraprocedural guidance (DSA or DSA with TEE). Periprocedural and follow-up outcomes were compared with investigate the feasibility and safety between the two cohorts. RESULTS: 71 patients and 67 patients were included in the DSA cohort and TEE cohort, respectively. Age and gender were comparable, despite the TEE cohort having a higher proportion of persistent AF (37 [55.2%] vs. 26 [36.6%]) and hemorrhage history (9 [13.4%] vs. 0). The procedure time of the DSA cohort was significantly reduced (95.7 ± 27.6 vs. 108.9 ± 30.3 min, p = .018), with a nonsignificant longer fluoroscopic time (15.2 ± 5.4 vs. 14.4 ± 7.1 min, p = .074). And the overall incidence of peri-procedural complications was similar between cohorts. After an average of 24 months of clinical follow-up, only three patients in the TEE cohort had ≤3 mm residual flow (p = .62). Kaplan-Meier estimates showed nonsignificant differences between the cohorts for freedom from atrial arrhythmia (log-rank p = .964) and major adverse cardiovascular events (log-rank p = .502). CONCLUSIONS: Compared with DSA and TEE guidance, DSA-guided combined procedure could shorten the procedural time, while achieving similar periprocedural and long-term feasibility and safety.

[Effects of Green, Blue, and Blue-green Roofs on Runoff Quality].

Roofs occupy a great proportion of urban impervious surfaces, and the implementation of eco-roof construction in urban areas is beneficial to alleviate the ecological and environmental problems caused by rapid urbanization. In this study, different eco-roofs (i.e., 68.6%-90.7%, and 39.8%-54.5%, respectively. However, all the eco-roofs were sources of NO-3-N, DCr, DFe, and DNi. The blue roof was a sink of DCu (with a pollutant load reduction rate of 21.9%) and did not affect the cumulative load of PO3-4-P in runoff. However, the green roof and blue-green roof were the sources of PO3-4-P and DCu. The RQI value of the blue roof was the highest, followed by that of the blue-green roof and green roof. The RQI value of the green roof was significantly lower than that of the blue and blue-green roofs (P<0.05). These results indicated that the runoff quality of the blue roof was the best, whereas that of the green roof was the worst. Adding a storage layer to the green roofs could significantly improve the runoff quality. The results of this study provide scientific references for the selection and design of eco-roof facilities.

Tumor Microenvironments-Adaptive Apoptotic Effects of Cytidine 5'-monophosphate-Capped Gold Nanoclusters.

In the present work, cytidine 5'-monophosphate capped gold nanoclusters (AuNCs@CMP) are reported as a catalyst for redox reactions, which show both oxidase- and excellent peroxidase-like activity. When employing 3,3',5,5'-tetramethylbenzidine (TMB) as a substrate in the presence of hydrogen peroxide (H2O2), the maximum velocity (Vmax) was 175 × 10-8 M s-1in vitro. Besides, the AuNCs@CMP exhibited high catalytic activity for reactive oxygen species (ROS) generation with H2O2. Particularly, they also displayed excellent catalytic activity for ROS generation in tumor cells, being activated and promoted by the tumor microenvironment (TME). Consequently, the AuNCs@CMP show an excellent antitumor effect on HeLa and SW480 cells as assayed by flow cytometry. The antitumor mechanism of AuNCs@CMP was attributed to the high ROS generation based on the specific environments of the TME. Therefore, the present study provides TME-adaptive AuNCs@CMP with excellent mimetic peroxidase activity, producing significant ROS to kill the tumor cells in TME.

Patients With Larger Left Atrial Appendage Orifice Presented Worse Prognosis Contributed by Acute Heart Failure After Left Atrial Appendage Closure.

Background Left atrial appendage (LAA) closure (LAAC) could prevent stroke in patients with atrial fibrillation. However, LAAC may impair the compliance of the left atrium and result in poor prognosis. This study aimed to comparatively evaluate the prognosis of LAAC among patients with different sizes of LAA orifice. Methods and Results Three hundred two consecutive patients who underwent successful LAAC were included and divided into 4 groups based on LAA orifice size that was measured using transesophageal echocardiography. Clinical outcomes including thromboembolic events, major cardiocerebrovascular adverse events, and acute heart failure (AHF) were compared among 4 quartile groups and between propensity-score matched groups of large and small LAAs. Through follow-up of 39.6±8.4 months, survival of thromboembolic events was similar. Survival of major cardiocerebrovascular adverse events was significantly lower in the group with the largest LAA orifice (log-rank P<0.001), including a higher incidence of AHF with New York Heart Association class III to IV (21.4%, log-rank P=0.009). A large LAA orifice (by cutoff) could predict major cardiocerebrovascular adverse events (hazard ratio, 3.749 [95% CI, 2.074-6.779]) in most patients, except for subgroups of those aged <65 years, with paroxysmal atrial fibrillation, and/or with failed rhythm/rate control. Further compared with a propensity-score matched small-LAA group, the large-LAA orifice group still presented worse survival of AHF with New York Heart Association class III to IV (log-rank P=0.010). Conclusions Patients with a larger LAA orifice presented a worse prognosis after LAAC, including a higher incidence of AHF. A large LAA orifice could predict a post-LAAC AHF event in most patients, except for young patients, patients with paroxysmal atrial fibrillation, and/or with failed rhythm/rate control. Registration URL: clinicaltrials.gov; Unique identifier: NCT04185142.