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Background: Macroreentry stands as the predominant mechanism of typical and atypical flutter. Despite advances in mapping, many aspects of macroreentrant atrial tachycardia remain unsolved. In this translational study, we applied principles of topology to understand the activation patterns, entrainment characteristics, and ablation responses in a large clinical macroreentrant atrial tachycardia database., Methods: Because the atrium can be topologically seen as a closed sphere with holes, we used a computational fixed spherical mesh model with a finite number of holes to induce and analyze macroreentrant atrial tachycardia. The ensuing insights were used to interpret high-density activation maps, postpacing interval-tachycardia cycle length values (difference between postpacing interval and tachycardia cycle length), and ablation response in 131 cases of typical and atypical flutter (n=106 left atrium, n=25 right atrium)., Results: Modeling of macroreentrant atrial tachycardia revealed that reentry on closed surfaces consistently manifests itself as paired rotation and that an odd number of critical boundaries is mathematically impossible. Together with mathematical confirmation by the index theorem, this led to a unifying construct that could explain the number of loops, difference between postpacing interval and tachycardia cycle length values, and ablation outcomes (termination, no change, or prolongation in tachycardia cycle length) in all 131 cases., Conclusions: Combining topology with the index theorem offers a novel and cohesive framework for understanding and managing typical and atypical flutter.

Aims: Achieving acute and durable mitral isthmus (MI) block remains challenging using radiofrequency (RF) catheter ablation alone. Vein of Marshall (VoM) ethanolization results in chemical damage along the MI resulting in the creation of a durable transmural lesion with a very high rate of procedural block. However, no studies have systematically assessed the efficacy of MI ablation alone when no anatomical VoM is present., Methods and Results: Thirty seven patients without VoM evidenced after careful angiographic examination were included. Ablation parameters and result were compared with a matched control group in whom the posterior MI line was performed without assessing the presence of the VoM. Mitral isthmus block was achieved in 36 out of 37 patients without VoM (97%), with endocardial ablation only in 5/37 (14%) and combined endocardial and coronary sinus ablation in 32/37 patients (86%). There was a significant difference in the occurrence of block between patients without a VoM and the control group (97.3% vs. 65% respectively, P < 0.01), with a trend towards less needed RF {26 [interquartile range (IQR) 20-38] vs. 29 [IQR 19-40] tags [P = 0.8], 611 [IQR 443-805] vs. 746 [IQR 484-1193] seconds [P = 0.08]}., Conclusion: The absence of a VoM is associated with a very high rate of procedural block during posterior MI ablation. The higher rate of MI block in this specific population would also suggest the crucial role of the VoM (when present) in resistant MI block., Competing Interests: Conflict of interest: All authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Competing Interests: Conflict of interest: none declared.

Background: Idiopathic ventricular fibrillation (IVF) can be associated with undetected distinct conditions such as microstructural cardiomyopathic alterations (MiCM) or Purkinje (Purk) activities with structurally normal hearts., Objectives: This study sought to evaluate the characteristics of recurrent VF recorded on implantable defibrillator electrograms, associated with these substrates., Methods: This was a multicenter collaboration study. At 32 centers, we selected patients with an initial diagnosis of IVF and recurrent arrhythmia at follow-up without antiarrhythmic drugs, in whom mapping demonstrated Purk or MiCM substrate. We analyzed variables related to previous ectopy, sinus rate preceding VF, trigger, and initial VF cycle lengths. Logistic regression with cross validation was used to evaluate the performance of criteria to discriminate Purk or MiCM substrates., Results: Among 95 patients (35 women, age 35 ± 11 years) meeting the inclusion criteria, IVF was associated with MiCM in 41 and Purk in 54 patients. A total of 117 arrhythmia recurrences including 91% VF were recorded on defibrillator. Three variables were mostly discriminant. Sinus tachycardia (≤570 ms) was more frequent in MiCM (35.9% vs 13.4%, P = 0.014) whereas short-coupled (<350 ms) triggers were most frequent in Purk-related VF (95.5% vs 23.1%, P = 0.001), which also had shorter VFCLs (182 ± 15 ms vs 215 ± 24 ms, P < 0.001).The multivariable combination provided the highest prediction (accuracy = 0.93 ± 0.05, range 0.833-1.000), discriminating 81% of IVF substrates with a high probability (>80%). Ectopy were inconsistently present before VF., Conclusions: Characteristics of arrhythmia recurrences on implantable cardioverter- defibrillator provide phenotypic markers of the distinct and hidden substrates underlying IVF. These findings have significant clinical and genetic implications., Competing Interests: Funding Support and Author Disclosures Dr Haissaguerre has received grant support from Biosense Webster. Dr Marijon has received grant support and consulting fees from Medtronic, Boston Scientific, Abbott, Microport, Biotronik, and Zoll. Pr Gandjbakhch has received lecture fees from Biotronik; and consulting fees from Medtronic, Microport, and Abbott. Dr Tilz is a consultant for Boston Scientific, Biotronik, Biosense Webster, and Abbott Medical; has received speaker honoraria from Boston Scientific, Biotronik, Biosense Webster, Abbott Medical, and Lifetech; and has received research grants from Abbott, Biosense Webster, and Lifetech. Dr Roten has received research grants from Medtronic, the Swiss National Foundation, the Swiss Heart Foundation, the Immanuel and Ilse Straub Foundation, and the Sitem Insel Support Fund, all for work outside the submitted study; and has received speaker/consulting honoraria from Abbott and Medtronic. Dr Reichlin has receivedresearch grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the Sitem Insel support funds, Biotronik, Boston-Scientific, and Medtronic, all for work outside the submitted study; and has received speaker/consulting honoraria or travel support from Abbott/SJM, Biosense-Webster, Biotronik, Boston-Scientific, and Medtronic, all for work outside the submitted study. Support for his institution’s fellowship program from Abbott/SJM, Biosense-Webster, Biotronik, Boston-Scientific, and Medtronic for work outside the submitted study. Dr Sacher has receivedspeaking honorarium from Abbott, Boston Scientific, and Biosense Webster; and equity from InHeart. Dr Nogami has received lecture fees from Abbott; and endowments from Medtronic. Dr Massoullié has received lecture fees from Boston Scientific, Biosense Webster, and Abbot. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Esophageal safety following radiofrequency (RF) left atrial (LA) linear ablation has not been established. To determine the esophageal safety profile of LA linear RF lesions, we performed systematic esophagogastroduodenoscopy in all patients with intraesophageal temperature rise (ITR) ≥ 38.5°C., Methods and Results: Between December 2021 and July 2023, a total of 200 consecutive patients with atrial tachyarrhythmia (ATA) underwent linear ablation with posterior dome (roof or floor) or posterior mitral isthmus line transection. Patients with ITR ≥ 38.5°C were scheduled for esophageal endoscopy ~3 weeks after ablation. Patient and ATA characteristics, procedural parameters, endoscopy findings and ablation lesion data were collected and analyzed. One hundred thirty-three out of 200 (67%) patients showed ITR ≥ 38.5°C during LA linear ablation. ITR (with maximal temperature of 45.7°C) was more frequently observed during floor line ablation (82% of cases). ITR was less observed during roof line ablation (34%) and posterior mitral isthmus ablation (4%). Endoscopy, performed in 115 patients after 24 ± 10 days, showed esophageal ulceration in four patients (two patients Kansas City classification [KCC] 2a and two patients KCC 2b). No patient showed esophageal perforation or fistula., Conclusion: Temperature rise during LA linear ablation is frequent and ulceration risk exists, particularly when floor line is performed. Safety measures are needed to avoid potential severe complications like esophageal perforation and fistula., (© 2024 Wiley Periodicals LLC.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Introduction: Through systematic scientific rigor, the CLOSE guided workflow was developed and has been shown to improve pulmonary vein isolation durability. However, this technique was developed at a time when using power-controlled ablation catheters with conventional power ranges was the norm. There has been increased adoption of a high-power and very high-power short-duration ablation practice propelled by the availability of the temperature-controlled radiofrequency QDOT MICRO catheter., Methods: There are fundamental differences in biophysics between very high-powered temperature guided ablation and conventional ablation strategy that may impact patient outcomes. The catheter's design and ablation modes offer flexibility in technique while accommodating the individual operator's clinical discretion and preference to deliver a durable, transmural, and contiguous lesion set., Results: Here, we provide recommendations for 3 different workflows using the QDOT MICRO catheter in a step-by-step manner for pulmonary vein isolation based on our cumulative experience as early adopters of the technology and the data available in the scientific literature., Conclusions: With standardization, temperature-controlled ablation with the QDOT MICRO catheter provides operators the flexibility of implementing different ablation strategies to ensure durable contiguous pulmonary vein isolation depending on patient characteristics., (© 2024 Wiley Periodicals LLC.)

Background: Early recurrence of atrial tachyarrhythmia (ERAT) is associated with ablation-induced proarrhythmogenic inflammation; however, existing studies used intermittent monitoring or nonoptimized radiofrequency (RF) applications (noncontiguous or without ablation index target value)., Objective: The purpose of this study was to investigate the relationship between ERAT and late recurrence based on insertable cardiac monitor (ICM) data., Methods: We compiled data from Close-To-Cure and Close Maze studies, which enrolled patients who underwent RF ablation for paroxysmal or persistent atrial fibrillation (AF). All patients were implanted with an ICM 2-3 months before ablation., Results: We studied 165 patients (104 with paroxysmal AF, 61 with persistent AF). Over the 1-year follow-up period, 41 of the patients experienced late recurrence. The risk of late recurrence was higher in patients experiencing ERAT (hazard ratio [HR] 6.2; 95% confidence interval [CI] 3.0-13.0), with negative and positive predictive values of 90.5% and 45.7%, respectively. Median burden of AF during the blanking period was significantly higher in patients with late recurrence (7.9% [0.0%-99.6%]) compared to those without recurrence (0.0% [0.0%-6.0]; P <.001). For each 1% increase in AF burden during the blanking period, late recurrence increased by 4.6% (HR 1.046; 95% CI 1.035-1.059). The best tradeoff for predicting AF from ERAT occurrence was AF burden of 0.6% and last ERAT at 64 days., Conclusion: In patients ablated for paroxysmal and persistent AF with a durable RF lesion set and implanted with a continuous monitoring device, postablation early AF recurrence and burden significantly predict late recurrence. The post-AF ablation blanking period should be reduced to 2 months., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The outcomes of persistent atrial fibrillation (AF) ablation are modest with various adjunctive strategies beyond pulmonary vein isolation (PVI) yielding largely disappointing results in randomised controlled trials. Linear ablation is a commonly employed adjunct strategy but is limited by difficulty in achieving durable bidirectional block, particularly at the mitral isthmus. Epicardial connections play a role in AF initiation and perpetuation. The ligament of Marshall has been implicated as a source of AF triggers and is known to harbour sympathetic and parasympathetic nerve fibres that contribute to AF perpetuation. Ethanol infusion into the Vein of Marshall, a remnant of the superior vena cava and key component of the ligament of Marshall, may eliminate these AF triggers and can facilitate the ease of obtaining durable mitral isthmus block. While early trials have demonstrated the potential of Vein of Marshall 'ethanolisation' to reduce arrhythmia recurrence after persistent AF ablation, further randomised trials are needed to fully determine the potential long-term outcome benefits afforded by this technique.

Aims: Pulsed field ablation (PFA) is a promising ablation technique for pulmonary vein isolation (PVI) with appealing advantages over radiofrequency (RF) including speed, tissue selectivity, and the promise of enhanced durability. In this study, we determine the procedural performance, efficacy, safety, and durability of PFA and compare its performance with a dataset of optimized RF ablation., Methods and Results: After propensity score matching, we compared 161 patients who received optimized RF-guided PVI in the PowerPlus study (CLOSE protocol) with 161 patients undergoing PFA-guided PVI for paroxysmal or persistent atrial fibrillation (AF; pentaspline basket catheter). The median age was 65 years with 78% paroxysmal AF in the PFA group (comparable characteristics in the RF group). Pulsed field ablation-guided PVI was obtained in all patients with a procedure time of 47 min (vs. 71 min in RF, P < 0.0001) and a fluoroscopy time of 15 min (vs. 11 min in RF, P < 0.0001). One serious adverse event [transient ischaemic attack] occurred in a patient with thrombocytosis (0.6 vs. 0% in RF). During the 6-month follow-up, 24 and 27 patients experienced a recurrence with 20 and 11 repeat procedures in the PFA and the RF groups, respectively ( P = 0.6 and 0.09). High-density mapping revealed a status of 4 isolated veins in 7/20 patients in the PFA group and in 2/11 patients in the RF group (35 vs. 18%, P = 0.3)., Conclusion: Pulsed field ablation fulfils the promise of offering a short and safe PVI procedure, even when compared with optimized RF in experienced hands. Pulmonary vein reconnection is the dominant cause of recurrence and tempers the expectation of a high durability rate with PFA., Competing Interests: Conflict of interest: M.D. received speaker fees from Biosense Webster not related to this work. The other authors report no conflict of interest to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: This study aims to investigate the relationship between serum uric acid levels and endothelial function, oxidative stress, and hemodynamic parameters, and to determine if uric acid levels provide additional insights beyond traditional factors like ageing and hypertension in volunteers with low cardiovascular risk factors. Serum uric acid is known for its antioxidant properties, but it may also contribute to cardiovascular risk., Materials and Methods: The study enrolled 40 male participants, divided into three groups based on age and blood pressure status. Group 1 comprised younger participants, group 2 included older individuals without hypertension, and group 3 consisted of older patients with hypertension. The study assessed endothelial function using laser Doppler imaging and measured acetylcholine- and sodium nitroprusside-induced hyperaemia. The heat microcirculatory response was also examined in the presence of L-NAME, an inhibitor of NOS synthase. The study evaluated oxidative stress and arterial stiffness by measuring allantoin, angiotensin II, Homocitrulline/Lysine, and Chloro-Tyrosine/Tyrosine ratios, as well as by performing non-invasive measurements of aortic augmentation indexes and carotid-femoral pulse wave velocity., Results: The study found that uric acid levels did not differ significantly among the three groups. Augmentation indexes increased with ageing, but hypertension did not have an additional effect. Blood pressure and carotid-femoral pulse wave velocity differed among the groups, with the lowest values among younger participants and the highest values among older individuals with hypertension. Allantoin and angiotensin II levels did not differ among the groups. However, Homocitrulline/Lysine and Chloro-Tyrosine/Tyrosine ratios were significantly lower in young subjects. Correlation and multivariable analysis showed that uric acid had no effect on any of the studied parameters. Despite a strong association between ageing and systolic blood pressure with impaired endothelial function, oxidative stress, and arterial stiffness, only ageing retained a significant effect in the multivariable analysis., Conclusion: In healthy or hypertensive adults with normal renal function, serum uric acid appears to be a futile bystander in endothelial function, oxidative stress, and arterial stiffness, in contrast to ageing, which reduces NO bioavailability. This study suggests that traditional factors such as ageing and hypertension should be the focus of clinical assessment and management of cardiovascular risk, rather than uric acid levels.

Persistent atrial fibrillation (AF) is a diverse condition that includes various subtypes and underlying causes of arrhythmia. Progress made in catheter ablation technology in recent years has significantly enhanced the durability of ablation. Despite these advances however, the effectiveness of ablation in treating persistent AF is still relatively modest. Studies exploring the mechanisms behind persistent AF have identified substrate-driven focal and re-entrant sources within the atrial body as crucial in sustaining AF among individuals with persistent AF. Furthermore, the widespread adoption of atrial late gadolinium enhancement cardiac magnetic resonance (CMR) imaging and the ongoing refinement of invasive voltage mapping techniques have allowed for detailed assessment of fibrotic remodelling prior to or at the time of procedure. Translation into clinical practice, however, has yielded overall disappointing results. The clinical application of AF mapping in ablation procedures has not shown any substantial advantages beyond the use of pulmonary vein isolation (PVI) alone and adjunct ablation of fibrotic areas has yielded conflicting results in recent randomized trials. The emergence of pulsed field ablation represents a welcome development in the field and several studies have demonstrated an enhanced safety profile and increased procedural efficiency with this non-thermal energy modality. Pulsed field ablation also holds promise for safe and efficient substrate ablation beyond the pulmonary veins, but further trials are needed to assess its impact on longer term success rates. Continued advancements in our comprehension of AF mechanisms, alongside ongoing developments in catheter technology aimed at safe formation of transmural lesions, are essential for achieving better clinical outcomes for patients with persistent AF., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Background: In patients with persistent atrial fibrillation (PersAF), catheter ablation aiming for pulmonary vein isolation (PVI) is associated with moderate clinical effectiveness. We investigated the benefit of continuing previously ineffective class 1C or 3 antiarrhythmic drug therapy (ADT) in the setting of a standardized PVI-only ablation strategy., Methods: In this multicenter, randomized controlled study, patients with PersAF (≥7 days and <12 months) despite ADT were prospectively randomized 1:1 to PVI with ADT continued versus discontinued beyond the blanking period (ADT ON versus ADT OFF). Standardized catheter ablation was performed aiming for durable isolation with stable, contiguous, and optimized radio frequency applications encircling the pulmonary veins (CLOSE protocol). Clinical visits and 1-to-7-day Holter were performed at 3, 6, and 12 months. The primary end point was any documented atrial tachyarrhythmia lasting >30 seconds beyond 3 months. Prospectively defined secondary end points included repeat ablations, unscheduled arrhythmia-related visits, and quality of life among groups., Results: Of 200 PersAF patients, 98 were assigned to ADT OFF and 102 to ADT ON. The longest atrial fibrillation episode qualifying for PersAF was 28 (10-90) versus 30 (11-90) days. Clinical characteristics and procedural characteristics were similar. Recurrence of atrial tachyarrhythmia was comparable in both groups (20% OFF versus 21.2% ON). No differences were observed in repeat ablations and unscheduled arrhythmia-related visits. Marked improvement in quality of life was observed in both groups., Conclusions: In patients with PersAF, there is no benefit in continuing previously ineffective ADT beyond the blanking period after catheter ablation. The high success rate of PVI-only might be explained by the high rate of durable isolation after optimized PVI and the early stage of PersAF (POWDER-AF2)., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03437356., Competing Interests: Disclosures None.

Background: Persistent shock-resistant atrial fibrillation (AF) is a challenging entity, with modest results from catheter ablation according to conventional survival analysis., Objectives: The aim of this study was to determine the effect of catheter ablation on atrial tachyarrhythmia (ATA) burden in persistent AF patients undergoing first-time ablation with the use of an implantable cardiac monitor (ICM)., Methods: Patients with drug-resistant ongoing persistent AF and at least 1 previous failed cardioversion were implanted with an ICM 2 months before the procedure. All patients underwent pulmonary vein isolation with or without additional substrate ablation depending on the presence of self-terminating AF on ICM and left atrium size. Median AF burden before and after ablation, off antiarrhythmic medication, was determined from ICM recordings after review by 2 independent investigators., Results: Sixty patients were recruited (mean age 66 ± 9 years, 70% male). Mean left atrial diameter was 48 ± 6 mm and median CHA 2 DS 2 VASc score was 2. Ten patients (17%) unexpectedly demonstrated self-terminating AF before ablation. The median burden of ATA before ablation was 100% (95% CI: 19.6%-100%), decreasing to 0% (95% CI: 0%-95.8%) after ablation during the post-blanking follow-up period (median reduction 100%; 95% CI: 4%-100%; P < 0.001). Twenty-seven patients (45%) experienced recurrent ATA during 12-month follow-up. In these patients, median burden before ablation was 100% (95% CI: 26.9%-100%), decreasing to 11.4% (95% CI: 0.35%-99.7%) after ablation (P < 0.001). Quality of life improved significantly from baseline, driven by lack of recurrence., Conclusions: Patient-tailored catheter ablation results in a significant reduction in ATA burden (off antiarrhythmic medication) in shock-resistant persistent AF patients using ICMs implanted 2-months pre-procedure. These data suggest that conventional arrhythmia-free survival analysis does not capture the true impact of catheter ablation in this challenging cohort., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Very high-power, short-duration (90-W/4-second) ablation for pulmonary vein isolation (PVI) may reduce procedural times. However, shorter applications with higher power may impact lesion quality., Objectives: In this multicenter, randomized controlled trial, the authors compared procedural efficiency, efficacy, and safety of PVI using 90-W/4-second ablation to 35/50-W ablation., Methods: Patients with paroxysmal or persistent atrial fibrillation undergoing first-time PVI were randomized to pulmonary vein encirclement with contiguous applications using very high-power, short-duration applications (90 W over 4 seconds) or 35/50-W applications (titrated up to ablation index >550 anteriorly and >400 posteriorly). Prospective endpoints were procedural efficiency (procedure time and first-pass isolation), safety (including esophageal endoscopic evaluation), and 6-month effectiveness using repetitive Holter monitoring., Results: A total of 180 patients were randomized, 90 to the 90-W group (mean age: 64.2 ± 8.9 years) and 90 to the 35/50-W group (mean age: 62.3 ± 10.8 years). Procedural time was shorter in the 90-W group vs the 35/50-W group (70 [IQR: 60-80] minutes vs 75 [IQR: 65-88.3] minutes; P = 0.009). A nonsignificant trend towards lower rates of first-pass isolation was seen in the 90-W group (83.9% vs 90%; P = 0.0852). No major complications were observed in both groups with esophageal injury occurring in 1 patient per group. At 6 months, 17% of patients in the 90-W group vs 15% in the 35/50-W group experienced recurrent arrhythmia (P = 0.681)., Conclusions: Contiguous ablation using very high-power, short-duration applications results in a significant but modest reduction in procedure time with similar safety and 6-month efficacy vs a conventional approach. A hybrid approach combining both ablation modalities might be the most optimal strategy. (POWER PLUS [Very High Power Ablation in Patients With Atrial Fibrillation Schedule for a First Pulmonary Vein Isolation]; NCT04784013)., Competing Interests: Funding Support and Author Disclosures Dr Kobza has served as a consultant for Biosense-Webster, Biotronik, and Medtronic, not related to this work. Drs Duytschaever and Scherr have received speaker fees from Biosense Webster, not related to this work. Dr Manninger has received research grants from Biosense Webster, not related to this work., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The superior vena cava (SVC) is well described as one of the most common non-pulmonary vein (PV)-triggers for atrial tachyarrhythmias (ATA). In our study we evaluated a standardized approach for electrical isolation of the SVC from the right atrium using a horseshoe-shaped lesion set with optimized and contiguous ostial RF lesions. The results are promising, demonstrating a very high rate of acute SVC isolation in a safe and time efficient manner (mostly less than 10 min)., (© 2022 Wiley Periodicals LLC.)

Aims: Atrial fibrillation (AF) occurs frequently after mitral valve (MV) surgery. This study aims to evaluate the efficacy and long-term clinical outcomes after the first AF ablation in patients with prior MV surgery., Methods: Sixty consecutive patients with a history of MV surgery without MAZE referred to three European centers for a first AF ablation between 2007 and 2017 (group 1) were retrospectively enrolled. They were matched (propensity score match) with 60 patients referred for AF ablation without prior MV surgery (group 2)., Results: After the index ablation, 19 patients (31.7%) from group 1 and 24 (40%) from group 2 had no recurrence of atrial arrhythmias (ATa) ( p = 0.3). After 62 (48-84) months of follow-up and 2 (2-2) procedures, 90.0% of group 1 and 95.0% of group 2 patients were in sinus rhythm ( p = 0.49). In group 1, 19 (31.7%) patients had mitral stenosis, and 41 (68.3%) had mitral regurgitation. Twenty-seven (45.0%) patients underwent mechanical valve replacement and 33 (55.0%) MV annuloplasty. At the final follow-up, 28 (46.7%) and 33 (55.0%) patients were off antiarrhythmic drugs ( p = 0.46). ATa recurrence was seen more commonly in patients with prior MV surgery (54 vs. 22%, respectively, p < 0.05). No major complication occurred., Conclusion: Long-term freedom of atrial arrhythmias after atrial fibrillation catheter ablation is achievable and safe in patients with a history of mitral valve surgery. In AF patients without a history of mitral valve surgery, repeated procedures are needed to maintain sinus rhythm., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Almorad, O'Neill, Wielandts, Gillis, De Becker, Nakatani, De Asmundis, Iacopino, Pambrun, Marc, Jaïs, Haïssaguerre, Duytschaever, Chierchia, Derval and Knecht.)

Recurrent atrial tachycardia (AT) is a common phenomenon after catheter ablation for AF, particularly in the setting of additional substrate ablation, with many studies demonstrating gap-related macro re-entrant AT (predominantly mitral and roof dependent) to be the dominant mechanism. Although multiple inducible ATs after ablation of the clinical AT are commonly described at repeat procedures, the optimal ablation strategy, and procedural endpoints are unclear in this setting. A recent randomized study addressing the question of non-inducibility as a procedural endpoint demonstrated no additional benefits to the ablation of all induced, non-clinical ATs, but it was limited by small numbers and high rates of non-inducibility. Nevertheless, once ablation of the clinical AT has been successfully performed, ensuring durable linear block and PV isolation may be sufficient for the prevention of further AT. Durable linear block, particularly at the mitral isthmus, is difficult to achieve but may be facilitated by the real-time evaluation of lesion quality and contiguity and the novel technique of vein of Marshall ethanol infusion. Large-scale, randomized trials are needed, nonetheless, to fully assess the optimal ablation strategy in the setting of recurrent AT post-AF ablation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 O’Neill, De Becker, De Smet, Le Polain De Waroux, Tavernier, Duytschaever and Knecht.)

Chemerin is a multifunctional protein initially characterized in our laboratory as a chemoattractant factor for leukocyte populations. Its main functional receptor is CMKLR1. We identified previously chemerin as an anti-tumoral factor inhibiting the vascularization of tumor grafts. We show here that overexpression of bioactive chemerin in mice results in a reduction of the density of the retinal vascular network during its development and in adults. Chemerin did not affect vascular sprouting during the post-natal development of the network, but rather promoted endothelial cell apoptosis and vessel pruning. This phenotype was reversed to normal in CMKLR1-deficient mice, demonstrating the role of this receptor. Chemerin inhibited also neoangiogenesis in a model of pathological proliferative retinopathy, and in response to hind-limb ischemia. Mechanistically, PTEN and FOXO1 antagonists could almost completely restore the density of the retinal vasculature, suggesting the involvement of the PI3-kinase/AKT pathway in the chemerin-induced vessel regression process., (© 2021. The Author(s).)

We hypothesized acute moderate and drastic reductions in uric acid concentration exert different effects on arterial function in healthy normotensive and hypertensive adults. Thirty-six adults (aged 58 [55;63] years) with or without primary hypertension participated in a three-way, randomized, double-blind, crossover study in which [placebo] and [febuxostat] and [febuxostat and rasburicase] were administered. Febuxostat and rasburicase reduce the uric acid concentration by xanthine oxidoreductase inhibition and uric acid degradation into allantoin, respectively. Endothelial function was assessed in response to acetylcholine, sodium nitroprusside, heating (with and without nitric oxide synthase inhibition) using a laser Doppler imager. Arterial stiffness was determined by applanation tonometry, together with blood pressure, renin-angiotensin system activity, oxidative stress, and inflammation. Uric acid concentration was 5.1 [4.1;5.9], 1.9 [1.2;2.2] and 0.2 [0.2;0.3] mg/dL with [placebo], [febuxostat] and [febuxostat-rasburicase] treatments, respectively (p < 0.0001). Febuxostat improved endothelial response to heat particularly when nitric oxide synthase was inhibited (p < 0.05) and reduced diastolic and mean arterial pressure (p = 0.008 and 0.02, respectively). The augmentation index decreased with febuxostat (ANOVA p < 0.04). Myeloperoxidase activity profoundly decreased with febuxostat combined with rasburicase (p < 0.0001). When uric acid dropped, plasmatic antioxidant capacity markedly decreased, while superoxide dismutase activity increased (p < 0.0001). Other inflammatory and oxidant markers did not differ. Acute moderate hypouricemia encompasses minor improvements in endothelial function, blood pressure, and arterial stiffness. Clinical Trial Registration: NCT03395977, https://clinicaltrials.gov/ct2/show/NCT03395977., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background Uric acid (UA) is a plasmatic antioxidant that has possible effects on blood pressure. The effects of UA on endothelial function are unclear. We hypothesize that endothelial function is not impaired unless significant UA depletion is achieved through selective xanthine oxidase inhibition with febuxostat and recombinant uricase (rasburicase). Methods and Results Microvascular hyperemia, induced by iontophoresis of acetylcholine and sodium nitroprusside, and heating-induced local hyperemia after iontophoresis of saline and a specific nitric oxide synthase inhibitor were assessed by laser Doppler imaging. Blood pressure and renin-angiotensin system markers were measured, and arterial stiffness was assessed. CRP (C-reactive protein), allantoin, chlorotyrosine/tyrosine ratio, homocitrulline/lysine ratio, myeloperoxidase activity, malondialdehyde, and interleukin-8 were used to characterize inflammation and oxidative stress. Seventeen young healthy men were enrolled in a randomized, double-blind, placebo-controlled, 3-way crossover study. The 3 compared conditions were placebo, febuxostat alone, and febuxostat together with rasburicase. The allantoin (μmol/L)/UA (μmol/L) ratio differed between sessions ( P <0.0001). During the febuxostat-rasburicase session, heating-induced hyperemia became altered in the presence of nitric oxide synthase inhibition; and systolic blood pressure, angiotensin II, and myeloperoxidase activity decreased ( P ≤0.03 versus febuxostat). The aldosterone concentration decreased in the febuxostat-rasburicase group ( P =0.01). Malondialdehyde increased when UA concentration decreased (both P <0.01 for febuxostat and febuxostat-rasburicase versus placebo). Other parameters remained unchanged. Conclusions A large and short-term decrease in UA in humans alters heat-induced endothelium-dependent microvascular vasodilation, slightly reduces systolic blood pressure through renin-angiotensin system activity reduction, and markedly reduces myeloperoxidase activity when compared with moderate UA reduction. A moderate or severe hypouricemia leads to an increase in lipid peroxidation through loss of antioxidant capacity of plasma. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03395977.

: Uric acid levels are higher in humans than in other mammals. Best known as an extracellular antioxidant, uric acid also increases salt sensitivity, fat storage, and lipogenesis. Xanthine oxidase-related oxidative stress may also induce endothelial dysfunction and renal vasoconstriction. Renal structure abnormalities contribute to salt-sensitive and uric acid-independent hypertension. Maternal hyperuricemia during pregnancy and hyperuricemia early in life are likewise independent risk factors for hypertension. Genetic polymorphism is potentially involved in the activity of xanthine oxidoreductase, but further studies are needed. Xanthine oxidase inhibition consistently decreases blood pressure in younger hypertensive patients, albeit modestly. Hyperuricemia affects one out of five adults as a result of the Western diet, insulin resistance, and renal dysfunction. This review advocates lifestyle changes to maintain uric acid levels within the normal range in young (pre)hypertensive individuals or normotensives with a family history of hypertension, metabolic disorders, or obesity; moreover, antihypertensive medications that increase uric acid levels should be avoided.

Nucleotides play a role in inflammation processes: cAMP and cGMP in the endothelial barrier function, ADP in platelet aggregation, ATP and UTP in vasodilatation and/or vasoconstriction of blood vessels, UDP in macrophages activation. The aim of this study is to develop and validate a LC/MS-MS method able to quantify simultaneously nine nucleotides (AMP, cAMP, ADP, ATP, GMP, cGMP, UMP, UDP and UTP) in biological matrixes (cells and plasma). The method we developed, has lower LOQ's than others and has the main advantage to quantify all nucleotides within one single injection in less than 10 min. The measured nucleotides concentrations obtained with this method are similar to those obtained with assay kits commercially available. Analysis of plasma and red blood cells from healthy donors permits to estimate the physiological concentration of those nucleotides in human plasma and red blood cells, such information being poorly available in the literature. Furthermore, the protocol presented in this paper allowed us to observe that AMP, ADP, ATP concentrations are modified in human red blood cells and plasma after a venous stasis of 4 min compared to physiological blood circulation. Therefore, this specific method enables future studies on nucleotides implications in chronic inflammatory diseases but also in other pathologies where nucleotides are implicated in., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Propylene glycol and glycerol are electronic cigarettes vehicles allowing liquid vaporization and nicotine transport. The respective effects of these different constituents on the cardiovascular system are unknown. We assessed the differential effects of vehicles (propylene glycol and glycerol) and nicotine on microcirculatory function, arterial stiffness, hemodynamic parameters and oxidative stress. Twenty-five tobacco smokers were exposed to vaping with and without nicotine, and sham vaping, in a randomized, single blind, 3-period crossover design study. Neither sham-vaping nor vaping in the absence of nicotine resulted in modifications of cardiovascular parameters or oxidative stress. In contrast, vaping with nicotine: 1) impaired acetylcholine mediated vasodilation (mean ± standard error mean) (area under curve, perfusion unit (PU), 3385 ± 27PU to 2271 ± 27PU, p < 0.0001); 2) increased indices of arterial stiffness, namely augmentation index corrected for heart rhythm (-3.5 ± 1.5% to 1.9 ± 2.3%; p = 0.013) and pulse wave velocity (4.9 ± 0.1 m.s -1 to 5.3 ± 0 .1 m.s -1 ; p < 0.0001); 3) increased systolic and diastolic blood pressures as well as heart rate (all p < 0.0001) and finally; 4) raised plasma myeloperoxidase (median [interquartile range]) (13.6 ng.ml -1 [10-17.7] to 18.9 ng.ml -1 [12.2-54.4], p = 0.005). Our findings demonstrated that high temperature e-cigarette vehicle vaporization does not alter micro- and macro-vascular function, and oxidative stress, and that these effects are solely attributable to nicotine.

Atrial fibrillation (AF) and hypertension (HT) are expected to rapidly rise worldwide in the next few years. Important improvements in AF therapy are hampered by pro-arrhythmic and bleeding risks of current medications. Prevention of AF is an important matter as it will not only prevent the disease but also medications side effects, and it is likely to be cost effective. HT is a major contributor to AF. As a modifiable risk factor, its treatment might reduce new-onset AF, and recurrent AF after cardioversion or ablation as well. We review here the effect of HT treatment to prevent AF. Renin-angiotensin system (RAS) blockers prevent new-onset AF in patients at high cardiovascular risk, and especially so in heart failure patients. The evidence is less strong among hypertensive patients, except in the presence of left ventricular hypertrophy or if at high cardiovascular risk. In such circumstances, losartan or valsartan were more effective than atenolol or amlodipine. After medical or electrical cardioversion, RAS blockers favourably affect AF recurrence and this class of drug should figure among the prescribed antihypertensive medications. Last, the addition of renal denervation to pulmonary vein isolation may provide even further therapeutic opportunities in patients with refractory HT and AF., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Air pollution has recently been associated with the development of acute decompensated heart failure, but the underlying biological mechanisms remain unclear. A pulmonary vasoconstrictor effect of air pollution, combined with its systemic effects, may precipitate decompensated heart failure. The aim of the present study was to investigate the effects of acute exposure to diesel exhaust (DE) on pulmonary vascular resistance (PVR) under resting and stress conditions but also to determine whether air pollution may potentiate acquired pulmonary hypertension. Eighteen healthy male volunteers were exposed to ambient air (AA) or dilute DE with a particulate matter of <2.5 μm concentration of 300 μg/m(3) for 2 h in a randomized, crossover study design. The effects of DE on PVR, on the coefficient of distensibilty of pulmonary vessels (α), and on right and left ventricular function were evaluated at rest (n = 18), during dobutamine stress echocardiography (n = 10), and during exercise stress echocardiography performed in hypoxia (n = 8). Serum endothelin-1 and fractional exhaled nitric oxide were also measured. At rest, exposure to DE did not affect PVR. During dobutamine stress, the slope of the mean pulmonary artery pressure-cardiac output relationship increased from 2.8 ± 0.5 mmHg · min · l (-1) in AA to 3.9 ± 0.5 mmHg · min · l (-1) in DE (P < 0.05) and the α coefficient decreased from 0.96 ± 0.15 to 0.64 ± 0.12%/mmHg (P < 0.01). DE did not further enhance the hypoxia-related upper shift of the mean pulmonary artery pressure-cardiac output relationship. Exposure to DE did not affect serum endothelin-1 concentration or fractional exhaled nitric oxide. In conclusion, acute exposure to DE increased pulmonary vasomotor tone by decreasing the distensibility of pulmonary resistive vessels at high cardiac output., (Copyright © 2015 the American Physiological Society.)