Amyloplast sedimentation repolarizes LAZYs to achieve gravity sensing in plants.

Gravity controls directional growth of plants, and the classical starch-statolith hypothesis proposed more than a century ago postulates that amyloplast sedimentation in specialized cells initiates gravity sensing, but the molecular mechanism remains uncharacterized. The LAZY proteins are known as key regulators of gravitropism, and lazy mutants show striking gravitropic defects. Here, we report that gravistimulation by reorientation triggers mitogen-activated protein kinase (MAPK) signaling-mediated phosphorylation of Arabidopsis LAZY proteins basally polarized in root columella cells. Phosphorylation of LAZY increases its interaction with several translocons at the outer envelope membrane of chloroplasts (TOC) proteins on the surface of amyloplasts, facilitating enrichment of LAZY proteins on amyloplasts. Amyloplast sedimentation subsequently guides LAZY to relocate to the new lower side of the plasma membrane in columella cells, where LAZY induces asymmetrical auxin distribution and root differential growth. Together, this study provides a molecular interpretation for the starch-statolith hypothesis: the organelle-movement-triggered molecular polarity formation.

One-stop hybrid procedure combining catheter ablation and left atrial appendage closure increases long-term risk for adverse events in patients with atrial fibrillation.

INTRODUCTION: Combined catheter ablation (CA) and left atrial appendage closure (LAAC) have proven to be a feasible and safe strategy in treating patients with nonvalvular atrial fibrillation (AF). However, the interactions between CA and LAAC have not been systematically explored. We analyzed the impact of CA on long-term outcomes of LAAC in patients with AF treated with the hybrid procedure. METHODS: A total of 107 consecutive patients with AF who underwent LAAC were divided into two groups: group A (n = 61) included patients who underwent CA followed by LAAC during the same procedure and group B (n = 46) included patients who underwent LAAC only. All patients underwent systematic transesophageal echocardiography (TEE) follow-up. RESULTS: In group A, CA resulted in severe edema of the left atrial ridge (LAR), which manifested as an increase in LAR thickness from 4.6 ± 0.4 mm before CA to 6.8 ± 0.6 mm (P < .01) after CA. TEE at 45 days showed that the incidence of peri-device leakage was significantly higher in group A than in group B (45.9% vs 4.3%, P < .001). At the 12-month follow-up, the peri-device leakage rate remained higher in group A than in group B (14.8% vs 2.2%, P < .01). Three (4.9%) patients in group A experienced transient ischemia attacks; no events were reported in group B during the 1-year follow-up. CONCLUSION: Edema of LAR with the single-stage procedure that consists of CA followed by LAAC could result in increased peri-device leakage and decreased compression rate over time, which may be also associated with elevated risk profiles when compared with an LAAC-only procedure.

Identification of circumferential pulmonary vein isolation responders among patients with persistent atrial fibrillation: clinical value of the sequential low-dose ibutilide test.

AIMS: Circumferential pulmonary vein isolation can be effective as sole treatment for persistent atrial fibrillation. However, identifying those patients who will respond to this therapy remains a challenge. We investigated the clinical value of the sequential low-dose ibutilide test for identifying patients with persistent atrial fibrillation in whom pulmonary vein isolation is effective as sole therapy. METHODS AND RESULTS: In a prospective cohort of 180 consecutive patients with persistent atrial fibrillation, intravenous low-dose (0.004 mg/kg) ibutilide was administered 3 days before ablation and after the completion of circumferential pulmonary vein isolation. In patients in whom ibutilide did not terminate atrial fibrillation pre-procedurally, but successfully terminated it intraprocedurally, no further atrial substrate modification was performed. Pre-procedural low-dose ibutilide failed to terminate the arrhythmia in all patients with persistent atrial fibrillation, while pulmonary vein isolation ± low-dose ibutilide terminated persistent atrial fibrillation in 55 (30.6%) of them (PsAF group 1). The remaining 125 (69.4%) patients underwent electrogram-based ablation (PsAF Group 2). The control group comprised 379 consecutive patients with paroxysmal atrial fibrillation who underwent pulmonary vein isolation over the same period. At 24 months follow-up, 39 (70.9%) patients in PsAF Group 1 and 276 (72.8%) patients in the control group were free from atrial tachyarrhythmias (P = NS); the arrhythmia-free rates in both groups were higher than that in PsAF group 2 (58.4%, P = 0.005). CONCLUSION: The sequential low-dose ibutilide test is a simple method for identifying patients with persistent atrial fibrillation in whom pulmonary vein isolation alone is an appropriate treatment strategy.

Radiofrequency Catheter Ablation Versus Cryoballoon Ablation in the Treatment of Paroxysmal Atrial Fibrillation: A Cost-effectiveness Analysis in China.

PURPOSE: The aim of this study was to evaluate the cost-effectiveness of radiofrequency catheter ablation (RFCA) compared with cryoballoon (CB) ablation in the treatment of patients with paroxysmal atrial fibrillation (PAF) from the payer's perspective in China. METHODS: We constructed a cohort model, combining a 12-month decision-tree model with a lifetime Markov state-transition model, in a hypothetical cohort of patients with drug-refractory PAF managed with either RFCA or CB ablation, to compare the cost-effectiveness of the 2 procedures. Data related to clinical outcomes and costs in this model were obtained from a retrospective 12-month follow-up study in patients in China and from related literature. The incremental cost-effectiveness ratio (ICER) over a 10-year time period was calculated and compared against the willingness-to-pay (WTP) threshold. We used a 1-way sensitivity analysis and a probabilistic sensitivity analysis (PSA) to access the structural uncertainty and the parameter uncertainty, respectively. FINDINGS: Over a 10-year time horizon, the total costs per patient of RFCA and CB ablation were ¥98,164.04 (US $15,339.57; €13,058.94) and ¥107,542.37 ($16,805.07; €14,306.55), respectively, and quality-adjusted life-years (QALYs) gained were 5.47 and 5.43, respectively. The ICER ratio was -¥224,365.01 (-$35,060.32; -€29,847.68) per QALY, indicating that RFCA is associated with greater QALYs and lower costs than CB ablation. The 1-way sensitivity analysis demonstrated that the model results were most sensitive to the odds ratio of the atrial fibrillation recurrence within 12 months in the RFCA group versus the CB ablation group, the cost of RFCA, and the perioperative stroke risk with RFCA. According to the results of the PSA, RFCA was associated with a high probability of being cost-effective (99.48%) compared with CB ablation at a WTP threshold of ¥161,940 ($25,305.50; €21,543.17) per QALY. IMPLICATIONS: Our analysis indicates that RFCA is cost-saving compared with CB ablation in the treatment of patients with PAF in China, based on better QALYs and lower costs over a 10-year time horizon, from the payer's perspective.

The safety and efficacy of hybrid ablation for the treatment of atrial fibrillation: A meta-analysis.

INTRODUCTION: Hybrid ablation, an emerging therapy that combines surgical intervention and catheter ablation, has become a viable option for the treatment of persistent atrial fibrillation. In this analysis, we aimed to evaluate the safety and efficacy of hybrid ablation, as well as compare the outcomes of one-step and staged approaches. METHODS: We conducted a search in major online databases and selected the studies that met the inclusion criteria. The primary endpoint was defined as no episode of atrial fibrillation or atrial tachycardia lasting longer than 30 seconds without administration of antiarrhythmic drugs. RESULTS: Sixteen studies including 785 patients (paroxysmal atrial fibrillation, n = 83; persistent atrial fibrillation, n = 214; long-standing persistent atrial fibrillation, n = 488) were selected. Average history of atrial fibrillation was (5.0±1.6) years. The pooled proportion of patients who were arrhythmia-free at the primary endpoint was 73% (95% CI, 64%-81%, Cochran's Q, P<0.001; I2 = 81%). The pooled rate of severe short-term complications was 4% (95% CI, 2%-7%, Cochran's Q, P = 0.01; I2 = 51%). The success rate after one-step procedures (69%) was lower than that after staged procedures (78%). The staged approach could ultimately prove to be safer, although complication rates were relatively low for both approaches (2% and 5%, respectively). CONCLUSIONS: Hybrid ablation is an effective and generally safe procedure. The current data suggest that staged hybrid ablation could be the optimal approach, as it is associated with a higher success rate and a seemingly lower complication rate. Additional randomized controlled trials are necessary to confirm these results.