Outcomes of Surgical Ablation for Atrial Fibrillation in On- versus Off-pump Coronary Artery Bypass Grafting.

OBJECTIVES: A considerable number of patients undergoing coronary artery bypass grafting surgery suffer from atrial fibrillation and should be treated concomitantly. This manuscript evaluates the impact of on-pump versus off-pump bypass grafting on the applied lesion-set and rhythm outcome. METHODS: Between January 2017 and April 2020 patients who underwent combined bypass grafting and surgical ablation for atrial fibrillation were consecutively enrolled in the German CArdioSurgEry Atrial Fibrillation registry (CASE-AF, 17 centers). Data were prospectively collected. Follow-up was planned after one year. RESULTS: 224 Patients were enrolled. No differences in baseline characteristics were seen between on- and off-pump bypass grafting, especially not in type of atrial fibrillation and left atrial size. In the on-pump group (n = 171, 76%), pulmonary vein isolation and an extended left atrial lesion-set were performed more often compared to off-pump bypass grafting. (58% vs 26%, 33 vs 9%, respectively, p < 0.001). In off-pump bypass grafting a box isolating the atrial posterior wall was the dominant lesion (72% off-pump vs 42% on-pump, p < 0.001). Left-atrial appendage management was comparable in on-pump vs off-pump bypass grafting (94% vs 91%, p = 0.37). Sinus rhythm at follow-up was confirmed in 61% in the on-pump group and in 65% in the off-pump group (p = 0.66). No differences were seen in in-hospital or follow-up complication-rates between the two groups. CONCLUSIONS: In coronary artery bypass grafting patients undergoing concomitant atrial fibrillation ablation, our data suggests that the technique applied for myocardial revascularization (off-pump vs on-pump) leads to differences in the ablation lesion set, but not in safety and effectiveness.

Epicardial and endocardial surgical ablation of atrial fibrillation: outcomes from CASE-AF Registry.

OBJECTIVES: The German CArdioSurgEry Atrial Fibrillation Registry is a prospective, multicentric registry analysing outcomes of patients undergoing surgical ablation for atrial fibrillation as concomitant or stand-alone procedures. This data sub-analysis of the German CArdioSurgEry Atrial Fibrillation Registry aims to describe the in-hospital and 1-year outcomes after concomitant surgical ablation, based on 2 different ablation approaches, epicardial and endocardial surgical ablation. METHODS: Between January 2017 and April 2020, 17 German cardiosurgical units enrolled 763 consecutive patients after concomitant surgical ablation. In the epicardial group, 413 patients (54.1%), 95.6% underwent radiofrequency ablation. In the endocardial group, 350 patients (45.9%), 97.7% underwent cryoablation. 61.5% of patients in the epicardial group and 49.4% of patients in the endocardial group presenting with paroxysmal atrial fibrillation. Pre-, intra- and post-operative data were gathered. RESULTS: Upon discharge, 32.3% (n = 109) of patients after epicardial surgical ablation and 24.0% (n = 72) of patients after endocardial surgical ablation showed recurrence of atrial fibrillation. The in-hospital mortality rate was low, 2.2% (n = 9) in the epicardial and 2.9% (n = 10) in the endocardial group. The overall 1-year procedural success rate was 58.4% in the epicardial and 62.2% in the endocardial group, with significant symptom improvement in both groups. The 1-year mortality rate was 7.7% (n = 30) in epicardial and 5.0% (n = 17) in the endocardial group. CONCLUSIONS: Concomitant surgical ablation is safe and effective with significant improvement in patient symptoms and freedom from atrial fibrillation. Adequate cardiac rhythm monitoring should be prioritized for higher quality data acquisition.

Surgical Ablation of Atrial Fibrillation in High-Risk Patients: Success versus Risk.

BACKGROUND: Surgical atrial ablation is evaluated by surgeons in relation to the estimated surgical risk. We analyze whether high-risk patients (HRPs) experience risk escalation by ablation procedures. METHODS: The CASE-Atrial Fibrillation (AF) registry is a prospective, multicenter, all-comers registry of atrial ablation in cardiac surgery. We analyzed the 1-year outcome regarding survival and rhythm endpoints of 1,000 consecutive patients according to the operative risk classification (EuroSCORE II ≤ 2 vs. >2). RESULTS: Higher NYHA (New York Heart Association) score, ischemic heart failure, status poststroke, renal insufficiency, chronic obstructive pulmonary disease, and diabetes mellitus were strongly represented in HRPs. HRPs exhibit more left ventricular ejection fraction < 40% (19.2 vs. 8.8%; p < 0.001) but identical left atrial diameter and left ventricular end-diastolic diameter compared with low-risk patients (LRPs). CHA2DS-Vasc-score (2.4 ± 1 vs. 3.6 ± 1.5; p < 0.001), sternotomies, combination surgeries, coronary artery bypass graft, and mitral valve procedures were increased in HRPs. LRPs underwent stand-alone ablations as well. Ablation energy did not differ. Left atrial appendage closure was performed in up to 86.1% (mainly cut-and-sew procedures). Mortality corresponded to the original risk class without an escalation that may be related to ablation, stroke rate, or myocardial infarction. A total of 60.6% of HRPs versus 75.1% of LRPs were discharged in sinus rhythm. Long-term EHRA (European Heart Rhythm Association) score symptoms were lower in HRPs. Repeated rhythm therapies were rare. Additional antiarrhythmics received a minority without group dependency. A total of 1.6 versus 4.1% of HRPs (p = 0.042) underwent long-term stroke; excess mortality was not observed. Anticoagulation remained common in HRPs. CONCLUSION: Surgical risk and long-term mortality are determined by the underlying disease. In HRPs, freedom from AF and symptom relief can be achieved. Preoperative risk scores should not lead to withholding an ablation procedure.

Longer and better lives for patients with atrial fibrillation: the 9th AFNET/EHRA consensus conference.

AIMS: Recent trial data demonstrate beneficial effects of active rhythm management in patients with atrial fibrillation (AF) and support the concept that a low arrhythmia burden is associated with a low risk of AF-related complications. The aim of this document is to summarize the key outcomes of the 9th AFNET/EHRA Consensus Conference of the Atrial Fibrillation NETwork (AFNET) and the European Heart Rhythm Association (EHRA). METHODS AND RESULTS: Eighty-three international experts met in Münster for 2 days in September 2023. Key findings are as follows: (i) Active rhythm management should be part of the default initial treatment for all suitable patients with AF. (ii) Patients with device-detected AF have a low burden of AF and a low risk of stroke. Anticoagulation prevents some strokes and also increases major but non-lethal bleeding. (iii) More research is needed to improve stroke risk prediction in patients with AF, especially in those with a low AF burden. Biomolecules, genetics, and imaging can support this. (iv) The presence of AF should trigger systematic workup and comprehensive treatment of concomitant cardiovascular conditions. (v) Machine learning algorithms have been used to improve detection or likely development of AF. Cooperation between clinicians and data scientists is needed to leverage the potential of data science applications for patients with AF. CONCLUSIONS: Patients with AF and a low arrhythmia burden have a lower risk of stroke and other cardiovascular events than those with a high arrhythmia burden. Combining active rhythm control, anticoagulation, rate control, and therapy of concomitant cardiovascular conditions can improve the lives of patients with AF.

Endosperm cell death: roles and regulation in angiosperms.

Double fertilization in angiosperms results in the formation of a second zygote, the fertilized endosperm. Unlike its embryo sibling, the endosperm is a transient structure that eventually undergoes developmentally controlled programmed cell death (PCD) at specific time points of seed development or germination. The nature of endosperm PCD exhibits a considerable diversity, both across different angiosperm taxa and within distinct endosperm tissues. In endosperm-less species, PCD might cause central cell degeneration as a mechanism preventing the formation of a fertilized endosperm. In most other angiosperms, embryo growth necessitates the elimination of surrounding endosperm cells. Nevertheless, complete elimination of the endosperm is rare and, in most cases, specific endosperm tissues persist. In mature seeds, these persisting cells may be dead, such as the starchy endosperm in cereals, or remain alive to die only during germination, like the cereal aleurone or the endosperm of castor beans. In this review, we explore current knowledge surrounding the cellular, molecular, and genetic aspects of endosperm PCD, and the influence environmental stresses have on PCD processes. Overall, this review provides an exhaustive overview of endosperm PCD processes in angiosperms, shedding light on its diverse mechanisms and its significance in seed development and seedling establishment.

Surgical ablation of long-standing persistent atrial fibrillation: 1-year outcomes from the CArdioSurgEry Atrial Fibrillation (CASE-AF) registry.

OBJECTIVES: The CArdioSurgEry Atrial Fibrillation (CASE-AF) registry is a prospective, multicentre study for collecting and analysing real-world data of surgical atrial fibrillation (AF) treatment. This study aimed to evaluate outcomes of surgery for long-standing persistent AF at 1 year. METHODS: In total, 17 centres consecutively include all eligible patients with continuous AF lasting for ≥1 year. Exclusion criteria are missing informed consent or age <18 years. For patient-reported outcomes measures, the European Heart Rhythm Association score was used. No presence of AF (based on ECG findings including Holter ECG and/or implanted devices), no re-ablation, no further cardioversion and no rehospitalization due to AF after a 3-month blanking period defined no AF recurrence at 1 year. RESULTS: From January 2017 to January 2020, a total of 1115 patients were enrolled in CASE-AF. Of them, 202 patients (mean age 69.7 ± 7.8 years, 27.2% female) underwent surgical ablation of long-standing persistent AF (study cohort), mostly accompanied by left atrial appendage closure (n = 180 [89%], resection n = 75 [42%]) and predominantly performed as concomitant (n = 174 [86%]) and left atrial only procedure (n = 144 [71%]). Early mortality (30 days) was 2.0% and morbidity was low. At follow-up (median 14.4 months, interquartile range, 12.7-17.6 months, 100% complete), 106 patients (56%) had no AF recurrence and 93% of them were asymptomatic. AF recurrence was accompanied by AF-related rehospitalization (n = 12, P = 0.003), direct current shock cardioversion (n = 23, P < 0.001), AF ablation (n = 7, P = 0.003) and stroke (n = 3, P = 0.059). Multivariable analysis identified cryoablation, predominantly performed endocardially including additional left atrial (74%) and biatrial (42%) lesions, as a significant factor for freedom from AF recurrence (odds ratio 2.7, 95% confidence interval 1.07-6.79, P = 0.035). CONCLUSIONS: According to CASE-AF, surgical ablation of long-standing persistent AF is most effective when concomitantly performed using endocardial cryoablation. Ongoing follow-up allows further elucidation of efficacious treatment strategies.

Neutrophils for Revascularization Require Activation of CCR6 and CCL20 by TNFα.

BACKGROUND: Activation of immune-inflammatory pathways involving TNFα (tumor necrosis factor alpha) signaling is critical for revascularization and peripheral muscle tissue repair after ischemic injury. However, mechanisms of TNFα-driven inflammatory cascades directing recruitment of proangiogenic immune cells to sites of ischemia are unknown. METHODS: Muscle tissue revascularization after permanent femoral artery ligation was monitored in mutant mice by laser Doppler imaging and light sheet fluorescence microscopy. TNFα-mediated signaling and the role of the CCL20 (C-C motif chemokine ligand 20)-CCR6 (C-C chemokine receptor 6) axis for formation of new vessels was studied in vitro and in vivo using bone marrow transplantation, flow cytometry, as well as biochemical and molecular biological techniques. RESULTS: TNFα-mediated activation of TNFR (tumor necrosis factor receptor) 1 but not TNFR2 was found to be required for postischemic muscle tissue revascularization. Bone marrow-derived CCR6+ neutrophil granulocytes were identified as a previously undescribed TNFα-induced population of proangiogenic neutrophils, characterized by increased expression of VEGFA (vascular endothelial growth factor A). Mechanistically, postischemic activation of TNFR1 induced expression of the CCL20 in vascular cells and promoted translocation of the CCL20 receptor CCR6 to the cell surface of neutrophils, essentially conditioning VEGFA-expressing proangiogenic neutrophils for CCL20-dependent recruitment to sites of ischemia. Moreover, impaired revascularization of ischemic peripheral muscle tissue in diabetic mice was associated with reduced numbers of proangiogenic neutrophils and diminished CCL20 expression. Administration of recombinant CCL20 enhanced recruitment of proangiogenic neutrophils and improved revascularization of diabetic ischemic skeletal muscles, which was sustained by sequential treatment with fluvastatin. CONCLUSIONS: We demonstrate that site-specific activation of the CCL20-CCR6 axis via TNFα recruits proangiogenic VEGFA-expressing neutrophils to sites of ischemic injury for initiation of muscle tissue revascularization. The findings provide an attractive option for tissue revascularization, particularly under diabetic conditions.

Endosperm cell death promoted by NAC transcription factors facilitates embryo invasion in Arabidopsis.

In flowering plants, two fertilization products develop within the limited space of the seed: the embryo and the surrounding nutritive endosperm. The final size of the endosperm is modulated by the degree of embryo growth. In Arabidopsis thaliana, the endosperm expands rapidly after fertilization, but later gets invaded by the embryo that occupies most of the seed volume at maturity, surrounded by a single remaining aleurone-like endosperm layer.1,2,3,4 Embryo invasion is facilitated by the endosperm-expressed bHLH-type transcription factor ZHOUPI, which promotes weakening of endosperm cell walls.5,6 Endosperm elimination in zou mutants is delayed, and embryo growth is severely affected; the endosperm finally collapses around the dwarf embryo, causing the shriveled appearance of mature zou seeds.5,6,7 However, whether ZHOUPI facilitates mechanical endosperm destruction by the invading embryo or whether an active programmed cell death (PCD) process causes endosperm elimination has been subject to debate.2,8 Here we show that developmental PCD controlled by multiple NAC transcription factors in the embryo-adjacent endosperm promotes gradual endosperm elimination. Misexpressing the NAC transcription factor KIRA1 in the entire endosperm caused total endosperm elimination, generating aleurone-less mature seeds. Conversely, dominant and recessive higher-order NAC mutants led to delayed endosperm elimination and impaired cell corpse clearance. Promoting PCD in the zhoupi mutant partially rescued its embryo growth defects, while the endosperm in a zhoupi nac higher-order mutant persisted until seed desiccation. These data suggest that a combination of cell wall weakening and PCD jointly facilitates embryo invasion by an active auto-elimination of endosperm cells.

Efficacy and safety of hybrid epicardial and endocardial ablation versus endocardial ablation in patients with persistent and longstanding persistent atrial fibrillation: a randomised, controlled trial.

Background: Endocardial catheter ablation (CA) has limited long-term benefit for persistent and longstanding persistent atrial fibrillation (PersAF/LSPAF). We hypothesized hybrid epicardial-endocardial ablation (HA) would have superior effectiveness compared to CA, including repeat (rCA), in PersAF/LSPAF. Methods: CEASE-AF (NCT02695277) is a prospective, multi-center, randomized controlled trial. Nine hospitals in Poland, Czech Republic, Germany, United Kingdom, and the Netherlands enrolled eligible participants with symptomatic, drug refractory PersAF and left atrial diameter (LAD) > 4.0 cm or LSPAF. Randomization was 2:1 to HA or CA by an independent statistician and stratified by site. Treatment assignments were masked to the core rhythm monitoring laboratory. For HA, pulmonary veins (PV) and left posterior atrial wall were isolated with thoracoscopic epicardial ablation including left atrial appendage exclusion. Endocardial touch-up ablation was performed 91-180 days post-index procedure. For CA, endocardial PV isolation and optional substrate ablation were performed. rCA was permitted between days 91-180. Primary effectiveness was freedom from AF/atrial flutter/atrial tachycardia >30-s through 12-months absent class I/III anti-arrhythmic drugs except those not exceeding previously failed doses. It was assessed in the modified intention-to-treat (mITT) population who had the index procedure and follow-up data. Major complications were assessed in the ITT population who had the index procedure. Thirty-six month follow-up continues. Findings: Enrollment began November 20, 2015 and ended May 22, 2020. In 154 ITT patients (102 HA; 52 CA), 75% were male, mean age was 60.7 ± 7.9 years, mean LAD was 4.7 ± 0.4 cm, and 81% had PersAF. Primary effectiveness was 71.6% (68/95) in HA versus 39.2% (20/51) in CA (absolute benefit increase: 32.4% [95% CI 14.3%-48.0%], p < 0.001). Major complications through 30-days after index procedures plus 30-days after second stage/rCA were similar (HA: 7.8% [8/102] versus CA: 5.8% [3/52], p = 0.75). Interpretation: HA had superior effectiveness compared to CA/rCA in PersAF/LSPAF without significant procedural risk increase. Funding: AtriCure, Inc.

Unloading, ablation, bridging and transplant: different indications and treatments using the Impella 5.5 as longer-term circulatory support in one patient-an interdisciplinary case report.

Background: In patients with cardiogenic shock the clinical treatment often involves temporary mechanical circulatory support for initial haemodynamic stabilization to enable further assessment of therapeutic strategies. The surgically implanted Impella 5.5 can be used for several indications like ventricular unloading, haemodynamic support during high-risk interventions, and as a bridge-to-transplant strategy.We present an interdisciplinary managed case of using Impella 5.5 for multiple indications and treatment strategies in one patient. Case summary: A 66-year-old patient with known dilated cardiomyopathy was admitted with non-ST-elevation myocardial infarction and underwent urgent coronary bypass grafting. His native heart function did not recover and he experienced recurrent episodes of sustained ventricular tachycardia (VT) and electrical storm. He was evaluated for heart transplantation (OHT) and received a VT-ablation. However, he suffered an in-hospital cardiac arrest (IHCA) with subsequent implantation of an extracorporeal life support system (ECLS). After surgical placement of an Impella 5.5 due to left ventricular distension and pulmonary congestion, the ECLS was successfully weaned. He showed good neurological outcomes and underwent another high-risk VT-ablation. The patient was further stabilized under Impella 5.5 support in a bridge-to-transplant strategy. After 34 days he underwent a successful OHT. Discussion: In this interdisciplinary case report the surgically implanted Impella 5.5 as temporary mechanical circulatory support was used for multiple different indications and treatment strategies like ventricular unloading, haemodynamic support during high-risk interventions, and as bridge-to-transplant strategy in one patient.

Fertility loss in senescing Arabidopsis ovules is controlled by the maternal sporophyte via a NAC transcription factor triad.

Flowers have a species-specific fertile period during which pollination and fertilization have to occur to initiate seed and fruit development. Unpollinated flowers remain receptive for mere hours in some species, and up to several weeks in others before flower senescence terminates fertility. As such, floral longevity is a key trait subject to both natural selection and plant breeding. Within the flower, the life span of the ovule containing the female gametophyte is decisive for fertilization and the initiation of seed development. Here, we show that unfertilized ovules in Arabidopsis thaliana undergo a senescence program that generates morphological and molecular hallmarks of canonical programmed cell death processes in the sporophytically derived ovule integuments. Transcriptome profiling of isolated aging ovules revealed substantial transcriptomic reprogramming during ovule senescence, and identified up-regulated transcription factors as candidate regulators of these processes. Combined mutation of three most-up-regulated NAC (NAM, ATAF1/2, and CUC2) transcription factors, NAP/ANAC029, SHYG/ANAC047, and ORE1/ANAC092, caused a substantial delay in ovule senescence and an extension of fertility in Arabidopsis ovules. These results suggest that timing of ovule senescence and duration of gametophyte receptivity are subject to genetic regulation controlled by the maternal sporophyte.

Functional and developmental convergence in the reproductive "nurse cells" of flowering plants.

The successful sexual reproduction of flowering plants depends upon double fertilisation, during which pollen grains, produced within the male floral organ (the anther) deliver two sperm cells to the ovule, buried deep within the ovary, triggering the development of the embryo and the surrounding tissues of the seed. Although much attention has been given to pollen and embryo development, less has been focused on the supporting tissues surrounding these organisms as they develop, the tapetum and the endosperm. Intriguingly, despite their very different origins, these tissues appear to have converged functionally and developmentally. Here we will discuss this apparent convergence and its molecular and physiological basis.

Le succès de la reproduction des plantes à fleurs réside en la double fécondation, un processus au cours duquel les grains de pollen, produits à l'intérieur des pièces florales males (anthères), apportent 2 cellules spermatiques à l'ovule, enfouie profondément au sein de l'ovaire, déclenchant ainsi le développement de l'embryon et des tissus environnants de la graine. Bien qu'une attention particulière a été accordée au développement du grain de pollen et de l'embryon, les tissus qui les entourent et qui soutiennent leurs développements, respectivement le tapis et l'albumen, ont fait l'objet d'une attention moindre. De manière intrigante, ces tissus semblent avoir convergé au niveau de leur fonction et de leur développement malgré leurs origines très différentes. Nous disserterons ici les bases moléculaires et physiologiques de cette convergence apparente.

The German Cardiosurgery Atrial Fibrillation Registry: 1-Year Follow-up Outcomes.

OBJECTIVES: This study of German Cardiosurgery Atrial Fibrillation (CASE-AF) registry aims to describe the 1-year outcomes of patients undergoing ablative procedures for atrial fibrillation (AF) in a cardiosurgical setting. METHODS: Between January 2017 and April 2020, 17 German cardiosurgical units enrolled 1,000 consecutive patients undergoing concomitant or stand-alone ablation for AF. In-hospital and 1-year follow-up data were collected on web-based electronic case report forms. The protocol mandated telephone-based follow-up contact after 1 year. RESULTS: At 1-year follow-up (median, 14.5 months [12.6-18.2 months]), significant improvement (p < 0.0001) in baseline modified European Heart Rhythm Association Class I was reported in both concomitant and stand-alone patients. Follow-up examinations were completed in 97.9% of cases, and a sinus rhythm was reported in 60.2 and 63.6% of stand-alone and concomitant patients, respectively. Statistically significant factors determining late recurrence were female gender (p = 0.013), preoperative persistent AF (p < 0.0001), and presence of cardiac implantable electronic device (p = 0.011). All-cause mortality at 1 year was 1% (n = 1) in stand-alone patients and 6.7% (n = 58) in concomitant patients. CONCLUSION: Surgical ablation of AF is safe and provides satisfactory results at short-term follow-up, with significant improvement in patient symptoms. Adequate cardiac rhythm monitoring should be prioritized for higher quality data acquisition.