Artículos de revistas: "Anti-arrhythmic strategy"

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NAKAZATO, YUJI. "Current Strategy of Anti-arrhythmic Drug Therapy for Persistent Atrial Fibrillation". Juntendo Medical Journal 63, n.º 5 (2017): 373–77. http://dx.doi.org/10.14789/jmj.63.373.

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Bond, Richard, Brian Olshansky y Paulus Kirchhof. "Recent advances in rhythm control for atrial fibrillation". F1000Research 6 (3 de octubre de 2017): 1796. http://dx.doi.org/10.12688/f1000research.11061.1.

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Atrial fibrillation (AF) remains a difficult management problem. The restoration and maintenance of sinus rhythm—rhythm control therapy—can markedly improve symptoms and haemodynamics for patients who have paroxysmal or persistent AF, but some patients fare well with rate control alone. Sinus rhythm can be achieved with anti-arrhythmic drugs or electrical cardioversion, but the maintenance of sinus rhythm without recurrence is more challenging. Catheter ablation of the AF triggers is more effective than anti-arrhythmic drugs at maintaining sinus rhythm. Whilst pulmonary vein isolation is an effective strategy, other ablation targets are being evaluated to improve sinus rhythm maintenance, especially in patients with chronic forms of AF. Previously extensive ablation strategies have been used for patients with persistent AF, but a recent trial has shown that pulmonary vein isolation without additional ablation lesions is associated with outcomes similar to those of more extensive ablation. This has led to an increase in catheter-based technology to achieve durable pulmonary vein isolation. Furthermore, a combination of anti-arrhythmic drugs and catheter ablation seems useful to improve the effectiveness of rhythm control therapy. Two large ongoing trials evaluate whether a modern rhythm control therapy can improve prognosis in patients with AF.

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Wagner, Michael, Mirna S. Sadek, Nataliya Dybkova, Fleur E. Mason, Johann Klehr, Rebecca Firneburg, Eleder Cachorro et al. "Cellular Mechanisms of the Anti-Arrhythmic Effect of Cardiac PDE2 Overexpression". International Journal of Molecular Sciences 22, n.º 9 (1 de mayo de 2021): 4816. http://dx.doi.org/10.3390/ijms22094816.

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Background: Phosphodiesterases (PDE) critically regulate myocardial cAMP and cGMP levels. PDE2 is stimulated by cGMP to hydrolyze cAMP, mediating a negative crosstalk between both pathways. PDE2 upregulation in heart failure contributes to desensitization to β-adrenergic overstimulation. After isoprenaline (ISO) injections, PDE2 overexpressing mice (PDE2 OE) were protected against ventricular arrhythmia. Here, we investigate the mechanisms underlying the effects of PDE2 OE on susceptibility to arrhythmias. Methods: Cellular arrhythmia, ion currents, and Ca2+-sparks were assessed in ventricular cardiomyocytes from PDE2 OE and WT littermates. Results: Under basal conditions, action potential (AP) morphology were similar in PDE2 OE and WT. ISO stimulation significantly increased the incidence of afterdepolarizations and spontaneous APs in WT, which was markedly reduced in PDE2 OE. The ISO-induced increase in ICaL seen in WT was prevented in PDE2 OE. Moreover, the ISO-induced, Epac- and CaMKII-dependent increase in INaL and Ca2+-spark frequency was blunted in PDE2 OE, while the effect of direct Epac activation was similar in both groups. Finally, PDE2 inhibition facilitated arrhythmic events in ex vivo perfused WT hearts after reperfusion injury. Conclusion: Higher PDE2 abundance protects against ISO-induced cardiac arrhythmia by preventing the Epac- and CaMKII-mediated increases of cellular triggers. Thus, activating myocardial PDE2 may represent a novel intracellular anti-arrhythmic therapeutic strategy in HF.

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Mezache, Louisa, Gerard Nuovo y Rengasayee Veeraraghavan. "A Multipronged Microscopy Approach Identifies Common Anti-Arrhythmic Strategy for Atrial Fibrillation and Myocardial Infarction". Microscopy and Microanalysis 27, S1 (30 de julio de 2021): 572–73. http://dx.doi.org/10.1017/s1431927621002476.

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Ng, F. S., A. R. Lyon, I. T. Shadi, E. T. Y. Chang, R. A. Chowdhury, E. Dupont y N. S. Peters. "D Modulation of gap junctional coupling as an anti-arrhythmic strategy to prevent reperfusion ventricular arrhythmias". Heart 96, Suppl 1 (junio de 2010): A2.2—A3. http://dx.doi.org/10.1136/hrt.2010.196113.17.

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Mezache, Louisa, Gerard Nuovo y Rengasayee Veeraraghavan. "B-PO04-138 VASCULAR BARRIER PROTECTION: A COMMON ANTI-ARRHYTHMIC STRATEGY FOR ATRIAL FIBRILLATION AND MYOCARDIAL INFARCTION". Heart Rhythm 18, n.º 8 (agosto de 2021): S335—S336. http://dx.doi.org/10.1016/j.hrthm.2021.06.832.

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Huang, Weiting, Felix YJ Keng y Chi Keong Ching. "Rate or Rhythm Control of Atrial Fibrillation – Pearls for the Internist". Annals of the Academy of Medicine, Singapore 46, n.º 11 (15 de noviembre de 2017): 433–38. http://dx.doi.org/10.47102/annals-acadmedsg.v46n11p433.

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Atrial fibrillation is an epidemic in Asia that is increasingly prevalent. Apart from stroke risk stratification and management of anticoagulation, physicians managing this group of patients also need to determine an optimal strategy in terms of rate or rhythm control. With new techniques of catheter ablation to maintain patients in sinus rhythm, patients with atrial fibrillation now have more options for treatment, on top of pharmacological methods. This paper aims to review the current evidence for rate and rhythm control in both general patients and subgroups of interest commonly encountered in clinical practices such as obesity, heart failure and thyroid disease. Key words: Ablation, Anti-arrhythmic drugs, Stroke

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Brizzi, Antonella, Alfonso Trezza, Ottavia Spiga, Samuele Maramai, Francesco Scorzelli, Simona Saponara y Fabio Fusi. "2-Hydroxy-5-(3,5,7-trihydroxy-4-oxo-4H-chromen-2-yl)phenyl (E)-3-(4-hydroxy-3-methoxyphenyl)acrylate: Synthesis, In Silico Analysis and In Vitro Pharmacological Evaluation". Molbank 2021, n.º 3 (23 de julio de 2021): M1258. http://dx.doi.org/10.3390/m1258.

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Quercetin and ferulic acid are two phytochemicals extensively represented in the plant kingdom and daily consumed in considerable amounts through diets. Due to a common phenolic structure, these two molecules share several pharmacological properties, e.g., antioxidant and free radical scavenging, anti-cancer, anti-inflammatory, anti-arrhythmic, and vasorelaxant. The aim of the present work was the combination of the two molecules in a single chemical entity, conceivably endowed with more efficacious vasorelaxant activity. Preliminary in silico studies herein described suggested that the new hybrid compound bound spontaneously and with high affinity on the KCa1.1 channel. Thus, the synthesis of the 3′-ferulic ester derivative of quercetin was achieved and its structure confirmed by 1H- and 13C-NMR spectra, HSQC and HMBC experiments, mass spectrometry, and elementary analysis. The effect of the new hybrid compound on vascular KCa1.1 and CaV1.2 channels revealed a partial loss of the stimulatory activity that characterizes the parent compound quercetin. Therefore, further studies are necessary to identify a better strategy to improve the vascular properties of this flavonoid.

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Migliore, Federico, Giulia Mattesi, Alessandro Zorzi, Barbara Bauce, Ilaria Rigato, Domenico Corrado y Alberto Cipriani. "Arrhythmogenic Cardiomyopathy—Current Treatment and Future Options". Journal of Clinical Medicine 10, n.º 13 (22 de junio de 2021): 2750. http://dx.doi.org/10.3390/jcm10132750.

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Arrhythmogenic cardiomyopathy (ACM) is an inheritable heart muscle disease characterised pathologically by fibrofatty myocardial replacement and clinically by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). Although, in its original description, the disease was believed to predominantly involve the right ventricle, biventricular and left-dominant variants, in which the myocardial lesions affect in parallel or even mostly the left ventricle, are nowadays commonly observed. The clinical management of these patients has two main purposes: the prevention of SCD and the control of arrhythmic and heart failure (HF) events. An implantable cardioverter defibrillator (ICD) is the only proven lifesaving treatment, despite significant morbidity because of device-related complications and inappropriate shocks. Selection of patients who can benefit the most from ICD therapy is one of the most challenging issues in clinical practice. Risk stratification in ACM patients is mostly based on arrhythmic burden and ventricular dysfunction severity, although other clinical features resulting from electrocardiogram and imaging modalities such as cardiac magnetic resonance may have a role. Medical therapy is crucial for treatment of VAs and the prevention of negative ventricular remodelling. In this regard, the efficacy of novel anti-HF molecules and drugs acting on the inflammatory pathway in patients with ACM is, to date, unknown. Catheter ablation represents an effective strategy to treat ventricular tachycardia relapses and recurrent ICD shocks. The present review will address the current strategies for prevention of SCD and treatment of VAs and HF in patients with ACM.

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Lin, Jiunn-Cherng, Cheng-Hung Li, Yun-Yu Chen, Chi-Jen Weng, Yu-Shan Chien, Shang-Ju Wu, Chu-Pin Lo et al. "Rhythm Control Better Prevents Dementia than Rate Control Strategies in Patients with Atrial Fibrillation—A Nationwide Cohort Study". Journal of Personalized Medicine 12, n.º 4 (3 de abril de 2022): 572. http://dx.doi.org/10.3390/jpm12040572.

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Background: Atrial fibrillation (AF) increases the risk of dementia. Whether the pharmacological rhythm control of AF can reduce the risk of dementia compared to the rate control strategy remains unclear. We hypothesize that the rhythm control strategy is better than the rate control strategy in preventing dementia. Methods: AF patients aged ≥65 years were identified from the Taiwan National Health Insurance Database. Patients receiving anti-arrhythmic drugs at a cumulative defined daily dose (cDDD) of >30 within the first year of enrollment constituted the rhythm control group. Patients who used rate control medications for a cDDD of >30 constituted the rate control group. A multivariate Cox hazards regression model was used to determine the hazard ratio (HR) for dementia. Results: A total of 3382 AF patients (698 in the rhythm control group; 2684 in the rate control group) were analyzed. During a 4.86 ± 3.38 year follow-up period, 414 dementia events occurred. The rhythm control group had a lower rate of dementia than the rate control group (adjust HR: 0.75, p = 0.031). The rhythm control strategy reduced the risk of dementia particularly in those receiving aspirin (p = 0.03). Conclusions: In patients with AF, pharmacological rhythm control was associated with a lower risk of dementia than rate control over a long-term follow-up period, particularly in patients receiving aspirin treatment.

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Kossaify, Antoine. "Vernakalant in Atrial Fibrillation: A Relatively New Weapon in the Armamentarium Against an Old Enemy". Drug Target Insights 13 (enero de 2019): 117739281986111. http://dx.doi.org/10.1177/1177392819861114.

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Atrial fibrillation is the most common sustained cardiac arrhythmia, and its prevalence is increasing with age; also it is associated with significant morbidity and mortality. Rhythm control is advised in recent-onset atrial fibrillation, and in highly symptomatic patients, also in young and active individuals. Moreover, rhythm control is associated with lower incidence of progression to permanent atrial fibrillation. Vernakalant is a relatively new anti-arrhythmic drug that showed efficacy and safety in recent-onset atrial fibrillation. Vernakalant is indicated in atrial fibrillation (⩽7 days) in patients with no heart disease (class I, level A) or in patients with mild or moderate structural heart disease (class IIb, level B). Moreover, Vernakalant may be considered for recent-onset atrial fibrillation (⩽3 days) post cardiac surgery (class IIb, level B). Although it is mainly indicated in patients with recent-onset atrial fibrillation and with no structural heart disease, it can be given in moderate stable cardiac disease as alternative to Amiodarone. Similarly to electrical cardioversion, pharmacological cardioversion requires a minimal evaluation and cardioversion should be included in a comprehensive management strategy for better outcome.

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Liu, Daiqi, Xuyao Han, Zhiwei Zhang, Gary Tse, Qingmiao Shao y Tong Liu. "Role of Heat Shock Proteins in Atrial Fibrillation: From Molecular Mechanisms to Diagnostic and Therapeutic Opportunities". Cells 12, n.º 1 (30 de diciembre de 2022): 151. http://dx.doi.org/10.3390/cells12010151.

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Heat shock proteins (HSPs) are endogenous protective proteins and biomarkers of cell stress response, of which examples are HSP70, HSP60, HSP90, and small HSPs (HSPB). HSPs protect cells and organs, especially the cardiovascular system, against harmful and cytotoxic conditions. More recent attention has focused on the roles of HSPs in the irreversible remodeling of atrial fibrillation (AF), which is the most common arrhythmia in clinical practice and a significant contributor to mortality. In this review, we investigated the relationship between HSPs and atrial remodeling mechanisms in AF. PubMed was searched for studies using the terms “Heat Shock Proteins” and “Atrial Fibrillation” and their relevant abbreviations up to 10 July 2022. The results showed that HSPs have cytoprotective roles in atrial cardiomyocytes during AF by promoting reverse electrical and structural remodeling. Heat shock response (HSR) exhaustion, followed by low levels of HSPs, causes proteostasis derailment in cardiomyocytes, which is the basis of AF. Furthermore, potential implications of HSPs in the management of AF are discussed in detail. HSPs represent reliable biomarkers for predicting and staging AF. HSP inducers may serve as novel therapeutic modalities in postoperative AF. HSP induction, either by geranylgeranylacetone (GGA) or by other compounds presently in development, may therefore be an interesting new approach for upstream therapy for AF, a strategy that aims to prevent AF whilst minimizing the ventricular proarrhythmic risks of traditional anti-arrhythmic agents.

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Lomidze, N. N., V. A. Vaskovskiy, M. V. Yashkov, E. A. Artukhina y A. Sh Revishvili. "OPPORTUNITIES AND FUTURE PERSPECTIVES FOR REMOTE MONITORING OF PATIENTS WITH IMPLANTED DEVICES". Complex Issues of Cardiovascular Diseases 8, n.º 2 (23 de junio de 2019): 98–106. http://dx.doi.org/10.17802/2306-1278-2019-8-2-98-106.

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Today implantable cardiac devices (ICD) are advanced therapeutic and preventive tools ensuring the collection and transmission of statistical and diagnostic patient data. The information obtained from implanted devices allows analyzing patients’ condition, selecting optimal treatment strategy, predicting and preventing possible complications. The number of ICD recipients is rapidly growing. Over 1,000 devices per 1 million population are implanted in Europe and the US annually. In the Russian Federation this number reaches 300 devices per 1 million population. Routine medical checkups of patients with ICD should be performed 2–4 times a year, with an average length of about 20 minutes. It means that only in the Russian Federation physicians will have to work 20–40 thousand extra hours with a tendency towards its increase as this figure will grow simultaneously with growing patients’ number. Remote monitoring (RM) technologies may solve this problem. In 2000 Biotronik AG developed the world's first system for remote monitoring of anti-arrhythmic devices called the “Home Monitoring” system. It is based on the mobile RM of patients who received ICD. The information collected by the devices is transmitted to a special service center via mobile communication networks and after processing, the information is transferred to a physician’s website along with a text message and a fax. The information is instantly delivered from a patient to a physician. A closed information network "patient-service center-physician" was developed for the hospitals and their patients, providing a novel advanced monitoring and timely treatment of the patient.

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Haldar, Shouvik, Habib Rehman Khan, Vennela Boyalla, Ines Kralj-Hans, Simon Jones, Joanne Lord, Oluchukwu Onyimadu et al. "Catheter ablation vs. thoracoscopic surgical ablation in long-standing persistent atrial fibrillation: CASA-AF randomized controlled trial". European Heart Journal 41, n.º 47 (29 de agosto de 2020): 4471–80. http://dx.doi.org/10.1093/eurheartj/ehaa658.

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Abstract Aims Long-standing persistent atrial fibrillation (LSPAF) is challenging to treat with suboptimal catheter ablation (CA) outcomes. Thoracoscopic surgical ablation (SA) has shown promising efficacy in atrial fibrillation (AF). This multicentre randomized controlled trial tested whether SA was superior to CA as the first interventional strategy in de novo LSPAF. Methods and results We randomized 120 LSPAF patients to SA or CA. All patients underwent predetermined lesion sets and implantable loop recorder insertion. Primary outcome was single procedure freedom from AF/atrial tachycardia (AT) ≥30 s without anti-arrhythmic drugs at 12 months. Secondary outcomes included clinical success (≥75% reduction in AF/AT burden); procedure-related serious adverse events; changes in patients’ symptoms and quality-of-life scores; and cost-effectiveness. At 12 months, freedom from AF/AT was recorded in 26% (14/54) of patients in SA vs. 28% (17/60) in the CA group [OR 1.128, 95% CI (0.46–2.83), P = 0.83]. Reduction in AF/AT burden ≥75% was recorded in 67% (36/54) vs. 77% (46/60) [OR 1.13, 95% CI (0.67–4.08), P = 0.3] in SA and CA groups, respectively. Procedure-related serious adverse events within 30 days of intervention were reported in 15% (8/55) of patients in SA vs. 10% (6/60) in CA, P = 0.46. One death was reported after SA. Improvements in AF symptoms were greater following CA. Over 12 months, SA was more expensive and provided fewer quality-adjusted life-years (QALYs) compared with CA (0.78 vs. 0.85, P = 0.02). Conclusion Single procedure thoracoscopic SA is not superior to CA in treating LSPAF. Catheter ablation provided greater improvements in symptoms and accrued significantly more QALYs during follow-up than SA. Clinical Trial Registration ISRCTN18250790 and ClinicalTrials.gov: NCT02755688

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Berte, Benjamin, Gabriella Hilfiker, Federico Moccetti, Thomas Schefer, Vanessa Weberndörfer, Florim Cuculi, Stefan Toggweiler, Frank Ruschitzka y Richard Kobza. "Pulmonary vein isolation using ablation index vs. CLOSE protocol with a surround flow ablation catheter". EP Europace 22, n.º 1 (13 de septiembre de 2019): 84–89. http://dx.doi.org/10.1093/europace/euz244.

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Abstract Aims Pulmonary vein isolation (PVI) using ablation index (AI) incorporates stability, contact force (CF), time, and power. The CLOSE protocol combines AI and ≤6 mm interlesion distance. Safety concerns are raised about surround flow ablation catheters (STSF). To compare safety and effectiveness of an atrial fibrillation (AF) ablation strategy using AI vs. CLOSE protocol using STSF. Methods and results First cluster was treated using AI and second cluster using CLOSE. Procedural data, safety, and recurrence of any atrial tachycardia (AT) or AF >30 s were collected prospectively. All Classes 1c and III anti-arrhythmic drugs (AAD) were stopped after the blanking period. In total, all 215 consecutive patients [AI: 121 (paroxysmal: n = 97), CLOSE: n = 94 (paroxysmal: n = 74)] were included. Pulmonary vein isolation was reached in all in similar procedure duration (CLOSE: 107 ± 25 vs. AI: 102 ± 24 min; P = 0.1) and similar radiofrequency time (CLOSE: 36 ± 11 vs. AI: 37 ± 8 min; P = 0.4) but first pass isolation was higher in CLOSE vs. AI [left veins: 90% vs. 80%; P < 0.05 and right veins: 84% vs. 73%; P < 0.05]. Twelve-month off-AAD freedom of AF/AT was higher in CLOSE vs. AI [79% (paroxysmal: 85%) vs. 64% (paroxysmal: 68%); P < 0.05]. Only four patients (2%) without recurrence were on AAD during follow-up. Major complications were similar (CLOSE: 2.1% vs. AI: 2.5%; P = 0.87). Conclusion The CLOSE protocol is more effective than a PVI approach solely using AI, especially in paroxysmal AF. In this off-AAD study, 79% of patients were free from AF/AT during 12-month follow-up. The STSF catheter appears to be safe using conventional CLOSE targets.

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Sughimoto, Koichi, Kozo Matsuo, Koichiro Niwa, Yasutaka Kawasoe, Shigeru Tateno, Takeaki Shirai, Masashi Kabasawa y Masanao Ohba. "Fontan completions over 10 years after Glenn procedures". Cardiology in the Young 24, n.º 2 (27 de marzo de 2013): 290–96. http://dx.doi.org/10.1017/s1047951113000280.

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AbstractObjective: Despite the broadened indications for Fontan procedure, there are patients who could not proceed to Fontan procedure because of the strict Fontan criteria during the early period. Some patients suffer from post-Glenn complications such as hypoxia, arrhythmia, or fatigue with exertion long after the Glenn procedure. We explored the possibility of Fontan completion for those patients.Methods: Between 2004 and 2010, five consecutive patients aged between 13 and 31 years (median 21) underwent Fontan completion. These patients had been followed up for more than 10 years (10 to 13, median 11) after Glenn procedure as non-Fontan candidates. We summarise these patients retrospectively in terms of their pre-operative physiological condition, surgical strategy, and problems that these patients hold.Results: Pre-operative catheterisation showed pulmonary vascular resistance ranging from 0.9 to 3.7 (median 2.2), pulmonary to systemic flow ratio of 0.3 to 1.6 (median 0.9), and two patients had significant aortopulmonary collaterals. Extracardiac total cavopulmonary connections were performed in three patients, lateral tunnel total cavopulmonary connection in one patient, and intracardiac total cavopulmonary connection in one patient, without a surgical fenestration. Concomitant surgeries were required including valve surgeries – atrioventricular valve plasty in three patients and tricuspid valve replacement in one patient; systemic outflow tract obstruction release – Damus–Kaye–Stansel procedure in two patients and subaortic stenosis resection in one patient; and anti-arrhythmic therapies – maze procedure in two patients, cryoablation in two patients, and pacemaker implantation in two patients. All patients are now in New York Heart Association category I.Conclusion:Patients often suffer from post-Glenn complications. Of those, if they are re-examined carefully, some may have a chance to undergo Fontan completion and benefit from it. Multiple lesions such as atrioventricular valve regurgitation, systemic outflow obstruction, or arrhythmia should be surgically repaired concomitantly.

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Whitaker, John, Paul C. Zei, Shahreen Ahmad, Steven Niederer, Mark O'Neill y Christopher A. Rinaldi. "The effect of ionizing radiation through cardiac stereotactic body radiation therapy on myocardial tissue for refractory ventricular arrhythmias: A review". Frontiers in Cardiovascular Medicine 9 (15 de septiembre de 2022). http://dx.doi.org/10.3389/fcvm.2022.989886.

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Cardiac stereotactic body radiation therapy (cSBRT) is a non-invasive treatment modality that has been recently reported as an effective treatment for ventricular arrhythmias refractory to medical therapy and catheter ablation. The approach leverages tools developed and refined in radiation oncology, where experience has been accumulated in the treatment of a wide variety of malignant conditions. However, important differences exist between rapidly dividing malignant tumor cells and fully differentiated myocytes in pathologically remodeled ventricular myocardium, which represent the respective radiation targets. Despite its initial success, little is known about the radiobiology of the anti-arrhythmic effect cSBRT. Pre-clinical data indicates a late fibrotic effect of that appears between 3 and 4 months following cSBRT, which may result in conduction slowing and block. However, there is clear clinical evidence of an anti-arrhythmic effect of cSBRT that precedes the appearance of radiation induced fibrosis for which the mechanism is unclear. In addition, the data to date suggests that even the late anti-arrhythmic effect of cSBRT is not fully attributable to radiation.-induced fibrosis. Pre-clinical data has identified upregulation of proteins expected to result in both increased cell-to-cell coupling and excitability in the early post cSBRT period and demonstrated an associated increase in myocardial conduction velocity. These observations indicate a complex response to radiotherapy and highlight the lack of clarity regarding the different stages of the anti-arrhythmic mechanism of cSBRT. It may be speculated that in the future cSBRT therapy could be planned to deliver both early and late radiation effects titrated to optimize the combined anti-arrhythmic efficacy of the treatment. In addition to these outstanding mechanistic questions, the optimal patient selection, radiation modality, radiation dose and treatment planning strategy are currently being investigated. In this review, we consider the structural and functional effect of radiation on myocardium and the possible anti-arrhythmic mechanisms of cSBRT. Review of the published data highlights the exciting prospects for the development of knowledge and understanding in this area in which so many outstanding questions exist.

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Dunnington, Gansevoort H., Carrie L. Pierce, Susan Eisenberg, Liem L. Bing, Peter Chang-Sing, Daniel W. Kaiser, Shelby Burk, Linda C. Moulton y Armin Kiankhooy. "A heart-team hybrid approach for atrial fibrillation: a single-centre long-term clinical outcome cohort study". European Journal of Cardio-Thoracic Surgery, 13 de julio de 2021. http://dx.doi.org/10.1093/ejcts/ezab197.

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Abstract OBJECTIVES The Cox-maze IV is the gold standard for surgical ablation of atrial fibrillation (AF). A heart-team hybrid approach using selected epicardial thoracoscopic surgical ablations and completion endocardial ablations to replicate the Cox-maze IV lesion set has gained popularity and early results have been promising. We herein report our single-centre long-term clinical outcomes using the heart-team hybrid approach with 455 patients. METHODS From 1 March 2013 to 1 July 2019, we prospectively collected data on all patients referred to our heart team for rhythm-control strategy for AF. Baseline characteristics, procedural complications and long-term freedom from AF (FFAF) both on and off anti-arrhythmic drug therapy were analysed. Ambulatory monitoring (>7 days) was obtained at 3 months and annually thereafter. RESULTS Four hundred and fifty-five patients completed the hybrid approach. Four hundred and forty-five (97.8%) patients had non-paroxysmal AF (long-standing persistent AF n = 249, 54.7%; persistent AF n = 196, 43.1%; paroxysmal AF n = 10, 2.2%). Average duration of AF was 5.9 ± 6.1 years. Average left atrial diameter was 4.8 ± 0.8 cm. FFAF at 3, 12, 24 and 36 months was 92%, 87%, 81% and 72%, respectively. FFAF without the use of anti-arrhythmic medications was 75%, 81%, 76% and 66%. Any surgical complications occurred in 28 (6.1%) patients. CONCLUSIONS A heart-team hybrid strategy for the treatment of AF is safe and effective. In a predominantly non-paroxysmal population with AF, at the 3-year follow-up, FFAF in patients on and off anti-arrhythmic drugs approaches that of patients who had the Cox-maze IV.

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Al-Hadithi, Ali B. A. K. y Noel G. Boyle. "A Clinical Review of Ventricular Arrhythmias in Patients with Congestive Heart Failure". EMJ Cardiology, 6 de septiembre de 2019. http://dx.doi.org/10.33590/emjcardiol/10311539.

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Heart failure is an increasingly prevalent condition, which is associated with ventricular arrhythmias. The reduction in cardiac pumping efficiency leads to the activation of several compensatory mechanisms. These mechanisms eventually lead to cardiac remodelling and a decline in haemodynamic status, contributing to the formation of a substrate conducive to arrhythmias, including increased automaticity, triggered activity, and, most commonly, re-entry circuits. In turn, ventricular arrhythmias can lead to the worsening of heart failure. A diagnosis of heart failure and ventricular arrhythmias is obtained using the patient’s history, examination findings, and investigation results. A key tool in this is echocardiogram imaging, which visualises the cardiac chambers, determines ventricular ejection fraction, and identifies structural abnormalities. A reduction in ejection fraction is a significant risk factor for the development of ventricular arrhythmias. Arrhythmias are diagnosed by ECG, Holter monitoring, and telemetry or event monitoring, and should initially be treated by optimising the medical management of heart failure. Anti-arrhythmic drugs, including beta-blockers, are usually the first-line therapy. Sudden cardiac death is a significant cause of mortality in heart failure patients, and implantable cardioverter defibrillator devices are used in both primary and secondary prevention. Anti-arrhythmic drugs and catheter ablation are important adjunctives for minimising shock therapy. In addition, autonomic modulation may offer a novel method of controlling ventricular arrhythmias. The objective of this review is to provide a practical overview of this rapidly developing field in relation to current evidence regarding the underlying pathophysiology, burden of disease, and management strategies available.

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Mezache, Louisa, Gerard Nuovo y Rengasayee Veeraraghavan. "Abstract P333: The Vascular Barrier: A Common Anti-arrhythmic Target In Atrial Fibrillation And Myocardial Infarction". Circulation Research 129, Suppl_1 (3 de septiembre de 2021). http://dx.doi.org/10.1161/res.129.suppl_1.p333.

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Vascular leak is a major sequela of inflammation, which is associated with arrhythmic pathologies such as atrial fibrillation (AF) and myocardial infarction (MI). We recently demonstrated that the vascular leak-inducing cytokine vascular endothelial growth factor (VEGF; 90-580 pg/ml - levels found in AF patients) induces acute remodeling (30-60 minutes) of sodium channel (Na V 1.5) -rich intercalated disk (ID) nanodomains, disrupting their ultrastructure and prompting translocation of Na V 1.5 from these sites. This in turn disrupted impulse propagation and promoted arrhythmias in murine atria. Here, we tested the hypotheses that i) similar acute pro-arrhythmic remodeling occurs in the ventricles of MI patients, and ii) protecting the vascular barrier may prevent arrhythmias following an acute inflammatory insult. First, we examined myocardial samples from five human MI patients. VEGF was overexpressed in both cardiomyocytes and vascular endothelium in the border zone surrounding <6 month-old infarcts. Notably, co-localization analysis showed significantly reduced Na V 1.5 near both connexin43 and N-cadherin within the border zone in 1-, 3-, and 9-day-old infarcts, paralleling our observations in mouse atria. Next, we returned to our murine model of AF induced by acute inflammatory insult (100 pg/ml VEGF for 60 minutes) to test the antiarrhythmic efficacy of protecting the vascular endothelial barrier. Overall, median in vivo arrhythmia burden was higher in VEGF-treated mice relative to vehicle controls (7.5±11 vs. 0±6 s/hr). We tested two strategies shown to prevent vascular barrier breakdown: Blocking connexin43 hemichannels (αCT11 peptide) decreased in vivo arrhythmia burden to 0 ± 6.07 s/hr. Panx1-IL2 (a peptide inhibitor of Panx1 channels) treatment decreased also in vivo arrhythmia burden (0 ± 15.57 s/hr with 1.6 μM Panx1-IL2). Similar antiarrhythmic efficacy was also achieved with small molecule inhibitors of Cx43 and Panx1. These results highlight VEGF-induced vascular leak as a novel mechanism for acute arrhythmias both in the early stage AF and following MI. Indeed, this mechanism may contribute to post-MI AF. Importantly, vascular-barrier protection may be a viable strategy to prevent these arrhythmias.

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Bolderman, Robert W., Rob J. Hermans, Leonard M. Rademakers, Tim S. Jansen, Monique M. De Jong, Peter Bruin, Aylvin A. Dias, Frederik H. Van der Veen y Jos G. Maessen. "Abstract 4098: Epicardial Amiodarone-Releasing Hydrogel Reduces Inducibility of Atrial Fibrillation in Goats". Circulation 118, suppl_18 (28 de octubre de 2008). http://dx.doi.org/10.1161/circ.118.suppl_18.s_828.

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Amiodarone (AM) is one of the most effective anti-arrhythmic drugs to prevent postoperative atrial fibrillation (AF). However, due to systemic side effects, prophylactic AM therapy is only appropriate for patients at high risk for postoperative AF. This study addressed the hypothesis that local epicardial delivery of AM produces therapeutic myocardial drug concentrations, while systemic levels remain low. Goats (n=14) were instrumented with right atrial epicardial patch electrodes, and a PEG-based hydrogel with AM (1 mg/kg bw) (n=9) or without drug (n=5) was applied to the right atrial epicardium. AF inducibility was assessed up to 28 days in awake goats by applying burst stimuli. Myocardial and plasma AM concentrations were analysed by HPLC. AM-hydrogel produced higher subepicardial than subendocardial drug concentrations, which both remained therapeutic up to 21 days after hydrogel application (fig. 1a ). In this period, AF inducibility was significantly lower in the AM-hydrogel group compared to hydrogel alone (fig. 1b ; p<0.05). Plasma AM and metabolite levels were below detection limits (<30 ng/L) during the 28-day follow-up. Epicardial AM-releasing hydrogel produces sufficient myocardial drug concentrations to reduce AF inducibility up to 3 weeks, whereas plasma drug levels remain undetectably low. This study demonstrates that local delivery of anti-arrhythmic drugs is a feasible approach to obtain therapeutically effective myocardial drug concentrations, while minimizing risk for systemic side effects. Locally applied AM-releasing hydrogel may be a novel strategy to prevent postoperative AF. Figure 1a. Amiodarone Distribution in Right Atrium (n=5) Figure 1b. AF Inducibility After Hydrogel Application (mean + SD)

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Politi, Cecilia, Tiziana Ciarambino, Letizia Riva, Stefania Frasson, Donata Lucci, Gualberto Gussoni, Lucio Gonzini et al. "Sex-gender and atrial fibrillation treatment in the ATA-AF Study". Italian Journal of Medicine 10 (16 de febrero de 2016). http://dx.doi.org/10.4081/itjm.2016.649.

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Atrial fibrillation (AF) is the most common cardiac arrhythmia. This analysis aimed to determine the sex-gender differences in patients with AF enrolled in the observational ATAAF study. The study was conducted in 360 centers in Italy. During a 4-week period, all consecutive inpatients and outpatients aged ≥18 years, with a documented primary or secondary diagnosis of AF, were included. A total of 7148 patients (47% females) were enrolled. Females were significantly older, they more frequently needed assistance and were affected with severe cognitive impairment. The preferred anti-arrhythmic strategy in both genders was heart rate control (females: 54.7%, males: 48.4%, p75 was not (1.00, 95% CI 0.79-1.26). This study defines sex-gender differences in AF patients, including lower OAC prescription in females despite of higher thrombotic risk. Concomitant higher hemorrhagic risk and other characteristics that were more frequent in females (i.e. severe cognitive and functional impairment) may at least partly explain this trend towards gender-related under-prescription of OAC.

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Hazzy, Fandy y Ardian Rizal. "C65. Pace and Ablate as an Alternative Approach for Rate Control Strategy in Patient with Atrial Fibrillation". European Heart Journal Supplements 23, Supplement_F (1 de noviembre de 2021). http://dx.doi.org/10.1093/eurheartjsupp/suab125.064.

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Abstract Background AF patient with refractory to optimal medical therapy for rate or rhythm control, atrioventricular (AV) nodal ablation with permanent pacemaker (PPM) implantation is an effective strategy for symptomatic relief. Maintenance of controlled ventricular rate helps to avoid frequent exacerbations of CHF and tachycardia-mediated cardiomyopathy, and is also associated with improved quality of life. Case Summary Female 66-year-old suffered from Heart Failure exacerbations caused by paroxysmal AF with rapid ventricular response (RVR) with underlying hypertensive cardiovascular disease. Rhythm control strategy with drip Amiodarone induce sinus bradycardia with unstable hemodynamic, when drugs was stopped then AF RVR reappeared, we tried to rate control strategy with Digoxin but, she experienced same condition as before. She underwent a pragmatical technique AV nodal ablation with cardiac pacing for rate control and she had drastic improvement of symptoms within the next 24 h. Complete AV block was achieved after application of 2 radiofrequency energies over the anatomic AV node. A permanent pacemaker (PPM) was programmed to VVIR at the rate of 70 bpm. Discussion Conventional medical therapies, including beta-blockers, non-dihydropyridine calcium channel blockers, digoxin, and anti-arrhythmic drugs, may fail to control the ventricular rate. Atrioventricular junction ablation and pacing (AVJAP) can be applied for patients whom medication is inadequate or associated with side effects (Recommendation IIA). According to our case, AVJAP is possible but an attractive choice for some elderly patients who are not compliant with treatment or associated with dangerous side effect for patients.

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Wang, Tao, Wei Li, Qianqian Huang, Chuqiao Yuan, Liping Qu, Xiaohe Xiao y Wenjun Zou. "The Clinical Efficacy and Safety of 11 Commonly Used Treatment Strategies Improving Arrhythmia of CHD in China: A Network Meta-Analysis". Frontiers in Pharmacology 12 (20 de septiembre de 2021). http://dx.doi.org/10.3389/fphar.2021.741716.

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Purpose: Arrhythmia which as a common complication of CHD, has a high incidence. At present, more and more anti-arrhythmic drugs are used in clinical practice. However, which drug has the best efficacy and high safety is still unknown. Therefore, we decided to use NMA to solve this problem.Method: We searched CNKI, Wanfang database, VIP database, Pubmed, Embase and Cochrane libraries, and collected all RCTs of arrhythmia of CHD, and used RevMan (5.3) and Stata (13.0) to carry out this NMA. The primary outcome indicator of this study is efficiency; the secondary outcome indicator is the incidence of adverse reactions.Result: A total of 134 RCTs, 13,951 patients, and 11 treatment strategies were included in this NMA. The results show that all treatment strategies can effectively improve the arrhythmia of patients. Among them, PMA+AM, AM+AT, AM+WG have higher effective rates, and PMA+AM, WG+ME, SC+ME have better safety. The effectiveness and safety of the treatment strategies which combined TCM and chemical drugs, are significantly better than that of using chemical drugs alone.Conclusion: The treatment strategy of combination of multiple drugs usually has higher efficiency and safety. PMA+AM seems to be the most recommended treatment strategy. In addition, the rational combination of TCM and chemical drugs may provide potential benefit.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021229693.

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Crinion, D., M. H. S. Hassan Shariat, D. G. Gupta, E. E. G. Gul, B. G. Glover, J. H. Hashemi, H. A. Abdollah et al. "5203Ablation of scar-related ventricular tachycardia: paced electrogram feature analysis (PEFA) is a novel and effective substrate based strategy". European Heart Journal 40, Supplement_1 (1 de octubre de 2019). http://dx.doi.org/10.1093/eurheartj/ehz746.0061.

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Abstract Background Ablation of scar related ventricular tachycardia (VT) has been shown to be superior to escalation of drug therapy. However, the incremental benefit remains modest, with 42% experiencing recurrent shocks and 64% appropriate anti-tachycardia pacing (ATP) in the VANISH study. Improved ablation strategies are needed. Paced electrogram feature analysis (PEFA) is a novel substrate based ablation technique. Purpose To investigate the effectiveness of the PEFA based VT ablation technique. Methods A single centre, prospective study. Consecutive cases of scar related VT that had an implantable cardiac defibrillator (ICD) and no prior ablations were recruited. Close coupled pacing was performed at the right ventricular apex and the VT isthmus(es) identified on high density mapping catheters by increased electrogram (EGM) duration and latency. A algorithm was developed to identify the latest EGM component after the S2 pacing artefact,. This millisecond value was displayed on the geometry as a colour (PEFA map) (St Jude Ensite Precision Electroanatomic Mapping). PEFA identified VT isthmus sites were targeted for ablation (Figure 1). Follow up ICD interrogation data was utilized to assess for VT recurrence. Results A total of 20 patients were recruited. These comprised ischaemic cardiomyopathy (CM) (17/20), dilated CM (2/20), and arrhythmogenic CM (1/20), male (18/20), and endocardial only approach (19/20). Mean age was 64.3±11.3 years, ejection fraction 24.4% ± 14.4, and ablation time was 1989.9±1078.1 seconds. Non-inducibility was demonstrated at the end of the case in 18/20. A class I or III anti-arrhythmic drug was continued in 50%. VT recurred in three cases (Day 28,30,55). One death occurred following a stroke on day 181. Mean follow up was 437.5±231.7 days. Figure 1 Conclusion This is the largest study to date on PEFA based VT ablation, the first to include non-ischaemic aetiologies, and reports a longer mean follow up. A high proportion of cases were non-inducible, and low VT recurrence rates were observed. PEFA appears to be a promising tool to guide VT ablation targets. Acknowledgement/Funding This research was funded in part by the Canadian Institute for Health Research (139080) and a grant from St. Jude Medical.

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Kim, Daehoon, Pil-Sung Yang, Seng Chan You, Jung-Hoon Sung, Eunsun Jang, Hee Tae Yu, Tae-Hoon Kim et al. "Association of rhythm control with incident dementia among patients with atrial fibrillation: a nationwide population-based cohort study". Age and Ageing 51, n.º 1 (enero de 2022). http://dx.doi.org/10.1093/ageing/afab248.

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Abstract Background Atrial fibrillation (AF) increases the risk of dementia, and catheter ablation of AF may be associated with a lower risk of dementia. We investigated the association of a rhythm-control strategy for AF with the risk of dementia, compared with a rate-control strategy. Methods This population-based cohort study included 41,135 patients with AF on anticoagulation who were newly treated with rhythm-control (anti-arrhythmic drugs or ablation) or rate-control strategies between 1 January 2005 and 31 December 2015 from the Korean National Health Insurance Service database. The primary outcome was all-cause dementia, which was compared using propensity score overlap weighting. Results In the study population (46.7% female; median age: 68 years), a total of 4,039 patients were diagnosed with dementia during a median follow-up of 51.7 months. Rhythm control, compared with rate control, was associated with decreased dementia risk (weighted incidence rate: 21.2 versus 25.2 per 1,000 person-years; subdistribution hazard ratio [sHR] 0.86, 95% confidence interval [CI] 0.80–0.93). The associations between rhythm control and decreased dementia risk were consistently observed even after censoring for incident stroke (sHR 0.89, 95% CI 0.82–0.97) and were more pronounced in relatively younger patients and those with lower CHA2DS2-VASc scores. Among dementia subtypes, rhythm control was associated with a lower risk of Alzheimer’s disease (sHR 0.86, 95% CI 0.79–0.95). Conclusions Among anticoagulated patients with AF, rhythm control was associated with a lower risk of dementia, compared with rate control. Initiating rhythm control in AF patients with fewer stroke risk factors might help prevent subsequent dementia.

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Zhang, Tao, Xiaojiao Du, Yue Gu, Yingying Dong, Wei Zhang, Zhirong Yuan, Xingmei Huang et al. "Analysis of Diurnal Variations in Heart Rate: Potential Applications for Chronobiology and Cardiovascular Medicine". Frontiers in Physiology 13 (8 de marzo de 2022). http://dx.doi.org/10.3389/fphys.2022.835198.

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Circadian factors likely influence the occurrence, development, therapy, and prognosis of cardiovascular diseases (CVDs). To determine the association between the heart rate (HR) diurnal parameters and CVD risks, we designed an analytical strategy to detect diurnal rhythms of HR using longitudinal data collected by clinically used Holter monitors and wearable devices. By combining in-house developed algorithms with existing analytical tools, we obtained trough phase and nocturnal variation in HR for different purposes. The analytical strategy is robust and also sensitive enough to identify variations in HR rhythms influenced by multiple effectors such as jet lag, geological location and altitude, and age from total 211 volunteers. A total of 10,094 sets of 24-h Holter ECG data were analyzed by stepwise partial correlation to determine the critical points of HR trough phase and nocturnal variation. The following HR diurnal patterns correlate with high CVD risk: arrhythmic pattern, anti-phase pattern, rhythmic patterns with trough phase less than 0 (extremely advanced diurnal pattern) or more than 5 (extremely delayed diurnal pattern), and nocturnal variation less than 2.75 (extremely low) or more than 26 (extremely high). In addition, HR trough phases from wearable devices were nearly identical to those from 24-h Holter monitoring from 12 volunteers by linear correlation and Bland-Altman analysis. Our analytical system provides useful information to identify functional diurnal patterns and parameters by monitoring personalized, HR-based diurnal changes. These findings have important implications for understanding how a regular heart diurnal pattern benefits cardiac function and raising the possibility of non-pharmacological intervention against circadian related CVDs. With the rapid expansion of wearable devices, public cardiovascular health can be promoted if the analytical strategy is widely applied.

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Maqoud, Fatima, Rosa Scala, Malvina Hoxha, Bruno Zappacosta y Domenico Tricarico. "ATP-sensitive potassium channel subunits in the neuroinflammation: novel drug targets in neurodegenerative disorders". CNS & Neurological Disorders - Drug Targets 20 (19 de enero de 2021). http://dx.doi.org/10.2174/1871527320666210119095626.

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: Arachidonic acids and its metabolites modulate plenty of ligand-gated, voltage-dependent ion channels, and metabolically regulated potassium channels including ATP-sensitive potassium channels (KATP). KATP channels are hetero-multimeric complexes of sulfonylureas receptors (SUR1, SUR2A or SUR2B) and the pore-forming subunits (Kir6.1 and Kir6.2) likewise expressed in the pre-post synapsis of neurons and inflammatory cells, thereby affecting their proliferation and activity. KATP channels are involved in amyloid-β (Aβ)-induced pathology, therefore emerging as therapeutic targets against Alzheimer’s and related diseases. The modulation of these channels can represent an innovative strategy for the treatment of neurodegenerative disorders; nevertheless, the currently available drugs are not selective for brain KATP channels and show contrasting effects. This phenomenon can be a consequence of the multiple physiological roles of the different varieties of KATP channels. Openings of cardiac and muscular KATP channel subunits, is protective against caspase-dependent atrophy in these tissues and some neurodegenerative disorders, whereas in some neuroinflammatory diseases benefits can be obtained through the inhibition of neuronal KATP channel subunits. For example, glibenclamide exerts an anti-inflammatory effect in respiratory, digestive, urological, and central nervous system (CNS) diseases, as well as in ischemia-reperfusion injury associated with abnormal SUR1-Trpm4/TNF-α or SUR1-Trpm4/ Nos2/ROS signaling. Despite this strategy is promising, glibenclamide may have limited clinical efficacy due to its unselective blocking action of SUR2A/B subunits also expressed in cardiovascular apparatus with pro-arrhythmic effects and SUR1 expressed in pancreatic beta cells with hypoglycemic risk. Alternatively, neuronal selective dual modulators showing agonist/antagonist actions on KATP channels can be an option.

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Subramanya, Vinita, J’Neka S. Claxton, Pamela L. Lutsey, Richard F. MacLehose, Lin Y. Chen, Alanna M. Chamberlain, Faye L. Norby y Alvaro Alonso. "Sex differences in treatment strategy and adverse outcomes among patients 75 and older with atrial fibrillation in the MarketScan database". BMC Cardiovascular Disorders 21, n.º 1 (diciembre de 2021). http://dx.doi.org/10.1186/s12872-021-02419-2.

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Abstract Background Women with atrial fibrillation (AF) experience greater symptomatology, worse quality of life, and have a higher risk of stroke as compared to men, but are less likely to receive rhythm control treatment. Whether these differences exist in elderly patients with AF, and whether sex modifies the effectiveness of rhythm versus rate control therapy has not been assessed. Methods We studied 135,850 men and 139,767 women aged ≥ 75 years diagnosed with AF in the MarketScan Medicare database between 2007 and 2015. Anticoagulant use was defined as use of warfarin or a direct oral anticoagulant. Rate control was defined as use of rate control medication or atrioventricular node ablation. Rhythm control was defined by use of anti-arrhythmic medication, catheter ablation or cardioversion. We used multivariable Poisson and Cox regression models to estimate the association of sex with treatment strategy and to determine whether the association of treatment strategy with adverse outcomes (bleeding, heart failure and stroke) differed by sex. Results At the time of AF, women were on average (SD) 83.8 (5.6) years old and men 82.5 (5.2) years, respectively. Compared to men, women were less likely to receive an anticoagulant or rhythm control treatment. Rhythm control (vs. rate) was associated with a greater risk for heart failure with a significantly stronger association in women (HR women = 1.41, 95% CI 1.34–1.49; HR men = 1.21, 95% CI 1.15–1.28, p < 0.0001 for interaction). No sex differences were observed for the association of treatment strategy with the risk of bleeding or stroke. Conclusion Sex differences exist in the treatment of AF among patients aged 75 years and older. Women are less likely to receive an anticoagulant and rhythm control treatment. Women were also at a greater risk of experiencing heart failure as compared to men, when treated with rhythm control strategies for AF. Efforts are needed to enhance use AF therapies among women. Future studies will need to delve into the mechanisms underlying these differences.

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Tang, Lisa Y., Nathaniel Hawkins, Laurent Macle, Kendall Ho, Roger Tam, Marc Deyell, Michael Lim, Paul Khairy y Jason Andrade. "Abstract 10366: Comparative Evaluations of Six Risk Scores Proposed for Baseline Prediction of Atrial Fibrillation Recurrence Post Catheter Ablation". Circulation 144, Suppl_1 (16 de noviembre de 2021). http://dx.doi.org/10.1161/circ.144.suppl_1.10366.

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Background: Being able to identify patients who are at risk of arrhythmia recurrence following catheter ablation is important for prognostication, shared-decision making, etc. While numerous predictive models for atrial fibrillation recurrence (AFR) have been proposed, few models have underwent external validation, and few studies compared multiple models using the same patient cohort. Aims: To evaluate six prediction models using an external dataset. Methods: Data from 632 patients was pooled from two independent clinical trials that enrolled patients with anti-arrhythmic drug refractory atrial fibrillation who underwent catheter ablation. Primary outcome for both trials was documented atrial tachyarrhythmia (atrial fibrillation/flutter/tachycardia as adjudicated by a clinical committee blinded to treatment strategy). We compared 6 models for predicting AFR recorded between days 91-365 post ablation using standard metrics and ranked them according to the positive and negative clinical utility indices. Results: As the figure shows, the top performing model was CHA2DS2-VASc, followed by DR-FLASH, albeit both achieved positive and negative predictive values lower than 65%. Many models achieved high specificity but low sensitivity, except for CAAP-AF, which achieved high sensitivity but low specificity. In summary, all achieved area under receiver operating characteristic curve lower than 56% and were deemed to have poor clinical utility (less than 0.5 out of 1) when evaluated on our dataset. Conclusion: All models performed poorly and had objectively limited clinical utility. There remains a need to develop generalizable tools for predicting post ablation AFR.

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Berkowitsch, A., J. Hutter, S. Zaltsberg, M. Tomic, P. Kahle, A. Hain, M. Kuniss y T. Neumann. "Impact of comorbidities and ablation strategy on outcome after pulmonary vein isolation with cryo-balloon in patients with non- paroxysmal atrial fibrillation". European Heart Journal 42, Supplement_1 (1 de octubre de 2021). http://dx.doi.org/10.1093/eurheartj/ehab724.0360.

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Abstract Background Presence of several comorbidities in patients with atrial fibrillation is well known, but impact of them on outcome after pulmonary vein isolation with cryo-balloon is not enough investigated. First aim of the study was analysis of the impact of comorbidities on long term outcome after PVI with cryo-balloon new generation (CBA) and secondary goal was evaluation of the impact of additional posterior roof ablation (PRA) in these patients. Methods Patients with non-paroxysmal AF ablated with CBA in our institution since May 2012 and completed follow up >3 months were enrolled in the study. The history of AF, cardiac comorbidities (CAD, Non ischemic-cardiomyopathy, heart insufficiency, right ventricular dysfunction) diabetes mellitus, and renal failure were assessed at admission, all patients received echocardiographic examination and blood test. After a single trans-septal access and PV angiography PVI was performed using a 28-mm CBA. Mapping of PV signals before, during, and after each cryo application was performed with a 3F lasso catheter. The procedural endpoint after PVI was defined as complete elimination of all fragmented signals at the PV antrum with verification of entrance and exit block. In some patients PRA was performed additionally to PVI at discretion of physician. The primary endpoint of this study was the first documented recurrence of atrial tachyarrhythmia (>30 sec.), hospitalization due to cardio-vascular cause, re-do procedure or re-administration of anti-arrhythmic drugs. Results Among 560 patients 78 (13.9%) had no comorbidity and 299 (53.4%) were lasted with >1 comorbidity. A total of 260 (46.4%) recurrences were obtained within median follow up of 28 (12–57) months. Female gender, long time from first diagnosis >12 months and cardiac comorbidity were revealed to be independent predictors for long term recurrences whereas additional PRA performed in 176 pts independently improved outcome (61.9% vs 49.7%). Conclusion Cardiac comorbidities increased probability of post ablation recurrences, but performing of additional posterior roof ablation improved outcome in our cohort. These results should be confirmed in multi-center randomized study Funding Acknowledgement Type of funding sources: None.

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Oka, T., Y. Koyama, K. Inoue, N. Tanaka, K. Tanaka, Y. Hirao, M. Okada et al. "Extensive ablation strategy for persistent atrial fibrillation impairs left atrial function but reduces recurrence rate". European Heart Journal 43, Supplement_2 (1 de octubre de 2022). http://dx.doi.org/10.1093/eurheartj/ehac544.462.

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Abstract Background In catheter ablation for persistent atrial fibrillation (AF), extensive ablation strategy, such as linear ablation and/or complex fractionated atrial electrogram (CFAE) ablation in addition to pulmonary vein isolation (PVI-plus), might impair left atrial function more severely than PVI-alone strategy. Purpose The aim of this study is to investigate the impact of extensive ablation strategy on LA function and assess the relationship between post-ablation LA function and recurrence. Methods This study is a post-hoc subanalysis of the EARNEST-PVI randomized controlled trial, which investigated the efficacy of the PVI-alone strategy in comparison with PVI-plus strategy for persistent AF. From the 497 participants of EARNEST-PVI trial, we enrolled 191 patients with full datasets of pre- and post-ablation cardiac computed tomography (CT) at our Hospital. Patients were divided into PVI-alone and PVI-plus groups. Within one month before and 3 months after ablation, LA volume index (LAVI) and LA emptying fraction (LAEF) were calculated by using the Comprehensive Cardiac Analysis software on the Extended Brilliance Workspace. We assessed i) post-ablation LA function, ii) AF/atrial tachycardia (AT) -free rate after single and final session, and iii) relationship between post-ablation LAEF and ablation success in each group. Results The indices of baseline LA remodeling were not different between PVI-alone (N=96) and PVI-plus groups (N=95) [LAVI: 71.4 (57.8, 82.0) vs. 68.7 (61.0, 78.1), P=0.92, LAEF: 13.7 (10.0, 17.4) vs. 13.0 (10.0, 16.9), PVI-alone vs. PVI-plus, P=0.78]. In overall patients, post-ablation LAEF did not differ among them [34.4 (26.1, 40.7) vs. 31.6 (26.0, 37.4), P=0.13]. In the analysis of patients showing sinus rhythm during the CT study, LAEF was significantly higher in PVI-alone (N=87) than in PVI-plus group (N=93) [35.7 (29.0, 41.0) vs. 31.7 (26.1, 37.5), P=0.011] (Figure 1A). AF/AT-free survival rate during median follow-up of 44 months was not different after first session (63.5% vs. 68.4%, P=0.33), while PVI-plus had a tendency towards higher success rate after final session (72.9% vs. 84.2%, P=0.053) (Figure 2). In receiver operating characteristics analysis for recurrence after first session, post-ablation decreased LAEF had significantly related to recurrence after PVI-alone (AUC: 0.733, P<0.0001), but not after PVI-plus (AUC: 0.567, P=0.31) (Figure 1B, C). Conclusion Compared with PVI-alone strategy, PVI-plus strategy damaged LA function more severely, but tended to be related to higher success rate. Post-ablation LA function was related to recurrence in PVI-alone, but not in PVI-plus. Extensive ablation might have additional anti-arrhythmic effect regardless of iatrogenic myocardial damage. Myocardial injury by extensive ablation may less attribute to recurrence than intrinsic damage of LA. Funding Acknowledgement Type of funding sources: None.

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Pak, HN, SY Yang, M. Kim, HT Yu, TH Kim, JS Uhm, BY Joung, MH Lee y JW Park. "Efficacy and safety of 50-60 Watt high-power short-duration radiofrequency catheter ablation of atrial fibrillation: A propensity score matching study". EP Europace 23, Supplement_3 (1 de mayo de 2021). http://dx.doi.org/10.1093/europace/euab116.210.

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Abstract Funding Acknowledgements Type of funding sources: None. Introduction Although high-power short-duration (HPSD) radiofrequency (RF) energy is commonly utilized in atrial fibrillation (AF) catheter ablation (CA), its efficacy, safety, and autonomic neural effects have not yet been evaluated in a large patient number. We compared HPSD-AFCA and conventional power (ConvP)-AFCA after propensity score matching. Methods Among 3,221 consecutive AF ablation patients, we included 1,720 patients (74.4% male, 59 ± 10 years old, 56.5% paroxysmal type) who underwent AFCA after propensity score matching: 430 in 50∼60W HPSD group vs. 1,290 in the ConvP group. We evaluated the procedural factors, complication risk, rhythm outcome, and 3-month heart rate variability (HRV) between the two groups and subgroups. Results Procedure times were significantly shorter in the HPSD group (p < 0.001), but the complication rate (p = 0.088) and the 3rd-month HRV did not differ between the two groups. At the 12-month follow-up, rhythm outcomes did not differ between the two groups (Overall, Log-rank p = 0.212; anti-arrhythmic drug off Log rank p = 0.246). These efficacy and safety outcomes were consistently similar regardless of the AF type or ablation lesion set. In the Cox regression analysis, the left atrium volume index measured by computed tomography (HR 1.009 [1.003-1.015]), p = 0.005) and extra-pulmonary vein triggers (HR 1.587 [1.033-2.440], p = 0.035) were independently associated with 1-year clinical recurrence, while the HPSD strategy was not (HR 1.188 [0.903-1.564], p = 0.218). Conclusions HPSD-AFCA significantly shortened the procedure time with similar rhythm outcomes, complication risks, and autonomic neural effects as ConvP-AFCA, regardless of the AF type or ablation lesion set. Abstract Figure.

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Mohanty, S., C. Trivedi, D. G. Della Rocca, C. Gianni, B. MacDonald, A. Mayedo, M. Bassiouny et al. "Long-term outcome of endocardial-only versus combined endocardial-epicardial homogenization of the scar for treatment of ventricular tachycardia in patients with ischemic cardiomyopathy". European Heart Journal 42, Supplement_1 (1 de octubre de 2021). http://dx.doi.org/10.1093/eurheartj/ehab724.0364.

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Abstract Introduction We investigated the ablation success of scar homogenization with combined (epicardial + endocardial) versus endocardial-only approach for ventricular tachycardia (VT) in patients with ischemic cardiomyopathy (ICM) at 5 years of follow-up. Method Consecutive ICM patients undergoing VT ablation at our center were classified into group 1: endocardial scar homogenization and group 2: endocardial +epicardial scar homogenization. Patients with previous open heart surgery were excluded. All patients underwent bipolar substrate mapping with standard scar settings defined as normal tissue >1.5 mV and severe scar <0.5 mV. Non-inducibility of monomorphic VT was the procedural endpoint in both groups. Patients were followed up twice a year for 5 years with implantable device interrogations. Results A total of 361 (Group 1: 291 and group 2: 70) patients were included in the study (mean age: 67 years, male: 88.4%). At 5 years, significantly higher number of patients from group 2 remained arrhythmia-free (figure 1). Of those patients, 87 (45%) and 51 (89%) from group 1 and 2 respectively were off-anti-arrhythmic drugs (AAD) (p<0.001). After adjusting for age, gender, hypertension, diabetes, and obstructive sleep apnea, scar homogenization using endo-epicardial approach was associated with 51% less recurrence compared to the endocardial ablation strategy (Hazard Ratio: 0.49, 95% CI: 0.27–0.89, p: 0.02). Conclusion In this series of patients with ischemic cardiomyopathy and VT, endo-epicardial scar homogenization was associated with a lower need for AAD and a significantly lower recurrence rate at 5-years of follow-up compared to the endocardial ablation alone. Funding Acknowledgement Type of funding sources: None. Figure 1

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Norrish, Gabrielle, Henry Chubb, Ella Field, Karen McLeod, Maria Ilina, Georgia Spentzou, Jan Till et al. "Clinical outcomes and programming strategies of implantable cardioverter-defibrillator devices in paediatric hypertrophic cardiomyopathy: a UK National Cohort Study". EP Europace, 22 de noviembre de 2020. http://dx.doi.org/10.1093/europace/euaa307.

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Abstract Aims Sudden cardiac death (SCD) is the most common mode of death in paediatric hypertrophic cardiomyopathy (HCM). This study describes the implant and programming strategies with clinical outcomes following implantable cardioverter-defibrillator (ICD) insertion in a well-characterized national paediatric HCM cohort. Methods and results Data from 90 patients undergoing ICD insertion at a median age 13 (±3.5) for primary (n = 67, 74%) or secondary prevention (n = 23, 26%) were collected from a retrospective, longitudinal multi-centre cohort of children (<16 years) with HCM from the UK. Seventy-six (84%) had an endovascular system [14 (18%) dual coil], 3 (3%) epicardial, and 11 (12%) subcutaneous system. Defibrillation threshold (DFT) testing was performed at implant in 68 (76%). Inadequate DFT in four led to implant adjustment in three patients. Over a median follow-up of 54 months (interquartile range 28–111), 25 (28%) patients had 53 appropriate therapies [ICD shock n = 45, anti-tachycardia pacing (ATP) n = 8], incidence rate 4.7 per 100 patient years (95% CI 2.9–7.6). Eight inappropriate therapies occurred in 7 (8%) patients (ICD shock n = 4, ATP n = 4), incidence rate 1.1/100 patient years (95% CI 0.4–2.5). Three patients (3%) died following arrhythmic events, despite a functioning device. Other device complications were seen in 28 patients (31%), including lead-related complications (n = 15) and infection (n = 10). No clinical, device, or programming characteristics predicted time to inappropriate therapy or lead complication. Conclusion In a large national cohort of paediatric HCM patients with an ICD, device and programming strategies varied widely. No particular strategy was associated with inappropriate therapies, missed/delayed therapies, or lead complications.

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Cataldi, C., M. Andronache, R. Eschalier, F. Jean, R. Bosle, M. Farhat y G. Massoullie. "P957Characteristics of atrial tachycardia after mitral surgey via biatrial trans-septal approach using high density mapping system". EP Europace 22, Supplement_1 (1 de junio de 2020). http://dx.doi.org/10.1093/europace/euaa162.222.

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Abstract Background The biatrial trans-septal approach (BTSa) ameliorates mitral valve (MV) exposure in difficult cases when routine left atriotomy doesnt"t allow it. Main steps are an oblique incision on the right atrium (RA), reaching medially the right pulmonary veins (PV), a septal incision from the fossa ovalis, extended up to reach the first incision, then on the left atrium (LA). Purpose We aim to study the arrhythmic burden in this post-surgical context, focusing on atrial tachycardia (AT), to investigate the complexity of several possible circuits. Methods All patients (>18yo) with previous MV surgery via BTSa for MV repair or replacement, who underwent ablation of AT from January 2017 to September 2019, were enrolled. Patients ablated for persistent or paroxysmal AF, or with AF during the index procedure were excluded. Patients with associated surgery on other valves or congenital defects, coronary, surgical or percutaneous rhythm interventions weren’t excluded. Electroanatomical mapping was created using 2 different high-density mapping system. Substrate and activation map and radio-frequency (RF) ablation (25-50W, Ablation Index target 400) were realized. Cartographies were analysed to evaluate AT re-entry circuit, critical isthmus (CI) location and characterization, atrial vulnerability. Procedural outcomes (AT termination, sinus rhythm (SR) restoration, anti-arrhythmic drugs (AAD) withdrawal), and peri-procedural complications were also evaluated. Results We enrolled 49 patients (median age 57 ± 15), finding a maximum of 5 AT per procedure (2 ± 1). A total of 112 AT were mapped: the majority (72%) were persistent AT, 8,2% common atrial flutter. Cycle length was 314 ± 74 msec, with proximal-distal activation of coronary sinus (78%). A multiple re-entry circuit was observed in 70% of index AT. We identified 152 critical isthmus (maximum 5 per procedure). Only 27,9% of our patients had a single CI; CTI was the most frequent one (n = 37), envolved in 33% of all AT, while BTS scars altogether were envolved in 65% AT. A complete AT circuit was mapped in the RA, the LA and both atria in respectively 49%, 11,5% and 39%AT. The distribution of CIs is shown in figure 1. Biatrial and left AT leads to superior procedure, RF and fluoroscopy duration (p <0,05). SR was restored in 93,4%of patients, requiring a DC shock in 4 cases. Immediate AAD withdrawal was achieved after 41%procedures. No pericardial, oesophageal, vascular or phrenic complication occurred. 4 pace-maker implantations were realized because of 3 interatrial, 2 AV block and a sinus node dysfunction. Conclusions AT occurring after a BTSa have a high prevalence of multiple re-entry circuits with multiple critical isthmus. Ablation in this context is feasible and safe but often requires a left atrial access. Mapping of both atria should be considered to identify critical isthmus and tailored ablation strategy. Abstract Figure 1. Critical Isthmus Distribution

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Van Der Heijden, CAJ, P. Segers, A. Masud, V. Weberndorfer, SM Chaldoupi, JGLM Luermans, S. Van Kuijk et al. "Minimally invasive atrial fibrillation ablation and left anterior descending bypass grafting". EP Europace 24, Supplement_1 (18 de mayo de 2022). http://dx.doi.org/10.1093/europace/euac053.278.

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Abstract Funding Acknowledgements Type of funding sources: None. Background Minimally invasive direct coronary artery bypass (MIDCAB) with robotic left internal mammary artery (LIMA) harvesting for a critical left anterior descending (LAD) stenosis and thoracoscopic ablation for atrial fibrillation (AF) may represent safe and effective alternatives to more invasive surgical approaches via sternotomy. Purpose To evaluate the feasibility, safety and efficacy of a MIDCAB procedure with concomitant thoracoscopic AF ablation. Methods We prospectively analysed all patients who underwent a minimally invasive, off-pump, MIDCAB through a left mini-thoracotomy with concomitant left-sided thoracoscopic AF ablation using a bipolar radio frequent clamp between 2017 and 2021. Results Twenty-three patients were included (age 69±8 years, BMI 29±4kg/m2, paroxysmal AF 61%, LAVI 42±11 ml/m2). All patients received an off-pump LIMA-LAD anastomosis. Ablation of the left (n=23) and right (n=22) pulmonary veins and box (n=21) was succeeded by epicardial validation of exit- and entrance block (n=22). No procedural complications were observed and complications during hospital admission and after discharge were: bleeding of the LIMA-LAD anastomosis n=1; myocardial infarction requiring percutaneous intervention of the LIMA-LAD n=1, respiratory insufficiency due to pleural effusion or atelectasis n=3, hospital readmission due to pleural- and pericardial effusion n=2. Duration of hospital stay was 6±2 days. After 12 months, 16/20 (80%) patients were in sinus rhythm when allowing anti-arrhythmic drugs and 18/20 (90%) patients were free from myocardial infarction. Conclusion Robot-assisted MIDCAB surgery for LIMA-LAD grafting concomitant with left-sided thoracoscopic AF ablation is a feasible, safe and efficacious minimally invasive treatment strategy for patients with a critical LAD stenosis and AF suitable for minimally invasive surgery.

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Panagopoulos, D., S. Nagy, S. Kim, M. Lampridou, N. Linton, D. Lefroy, Z. Whinnett et al. "P967Role of low voltage ablation in catheter ablation of patients with persistent AF- a single centre experience". EP Europace 22, Supplement_1 (1 de junio de 2020). http://dx.doi.org/10.1093/europace/euaa162.224.

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Abstract Funding Acknowledgements Research grant from Abbott Introduction We have recently described a novel evaluation of AF voltage which correlates better with MRI-DE defined scar than sinus rhythm voltage. We evaluated the clinical efficacy of additional voltage-based substrate modification in the Persistent AF patient cohort in a single centre case series. Methods 22 PsAF patients undergoing catheter ablation were recruited. Left atrial electroanatomical maps were created in AF before any ablation was performed in all patients. Mean peak to peak AF voltage mapping was undertaken using 8s segments of AF (<0.35mV). PVI was then performed in all patients after which, further ablation lesions were delivered on the underlying scar tissue (transection, box formation or homogenisation). Results Of the 22 patients currently under follow up, 16 patients are more than 12 months after their initial procedure. 11/16 patients have had no recurrence and no patient is currently on anti-arrhythmic medication. Conclusion From our series, 69% of PsAF patients remain arrhythmia free at one year follow up post blanking period with a single procedure. Ablation of low voltage areas appears to infer incremental benefit in the Persistent AF population. Table 1 Mean Age, yrs 64 ± 9 Male 19 (86.3) Diabetes mellitus 1 (4.5) Hypertension 7 (31.8) TIA/CVA 2 (9) Left ventricular EF ≥55% 22 (100.0) LA size (diameter, according to British Society of Echocardiography Guidelines) Normal -Mild 12 (54.5) Moderate - Severe 10 (45.5) Mean AF duration, months 24.2 ± 20.8 Current antiarrhythmic strategy Amiodarone 3 (13.6) Sotalol 1 (4.5) Current anticoagulation Warfarin 3 (13.6) Direct oral anticoagulants 19 (86.3) Values are mean ± SD or N (%) or duration in months ± SD AF = atrial fibrillation; CVA= cerebrovascular accident; EF = ejection fraction; LA = left atrium; TIA = transient ischaemic attack. Baseline characteristics of patients (n = 22) Abstract Figure. Ablation sets and AF Voltage

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Mezache, Louisa, Andrew Soltisz, Scott R. Johnstone, Brant Isakson y Rengasayee Veeraraghavan. "Abstract 120: Vascular Endothelial Barrier Protection Prevents Atrial Fibrillation By Preserving Cardiac Nanostructure". Arteriosclerosis, Thrombosis, and Vascular Biology 42, Suppl_1 (mayo de 2022). http://dx.doi.org/10.1161/atvb.42.suppl_1.120.

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Atrial fibrillation (AF) patients experience inflammation and vascular dysfunction and have elevated levels of cytokines that promote vascular leak and edema, such as vascular endothelial growth factor (VEGF). We previously identified edema-induced disruption of sodium channel (Na V 1.5) -rich intercalated disk (ID) nanodomains as a novel arrhythmia mechanism. Therefore, we hypothesized that: (i) VEGF-induced vascular leak acutely slows action potential propagation in the atria and increases arrhythmia risk by disrupting ID nanodomains, and (ii) protection of the vascular barrier can prevent vascular leak-induced atrial arrhythmias. Electron microscopy revealed ID nanodomain swelling, near both gap junctions (GJ) and mechanical junctions (MJ) following VEGF treatment (60 minutes) in mouse hearts. Super-resolution STORM and STED microscopy both revealed Na V 1.5 enrichment at GJ and MJ relative to other ID sites in control hearts. VEGF reduced Na V 1.5 enrichment at both sites, consistent with Na V 1.5 translocation from ID nanodomains. VEGF increased distance from GJs to 90% of Na V 1.5 signal (3.17μm vs. 0.47 μm in vehicle controls), measured by a distance transformation-based analysis of 3D confocal images of IDs. VEGF slowed atrial conduction (optical mapping) and increased atrial arrhythmia incidence (ECG) relative to vehicle controls in both ex vivo (80 vs 0%) and in vivo (70 vs 20%) studies. Overall, in vivo arrhythmia burden was higher in VEGF-treated mice (7.5±11 vs. 0±6s/hr in vehicle controls). Preserving the vascular barrier by blocking endothelial Panx1 channels (PxIL2P peptide) decreased VEGF-induced in vivo arrhythmia burden (0 ± 6.09 s/hr with 1.6 μM PxIL2P). Concurrently, distance from GJs to 90% of Na V 1.5 was restored to control levels (0.57μm) in these hearts. In summary, these results highlight inflammation-induced vascular leak as a novel AF mechanism, and suggest vascular barrier protection as an anti-arrhythmic strategy.

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Mol, D., MJ Mulder, R. Veenstra, CP Allaart, IE Hof, MJB Kemme, M. Khan et al. "Strategies for repeat ablation for atrial fibrillation: a multicentre comparison of non-pulmonary vein versus pulmonary vein target ablation". EP Europace 24, Supplement_1 (18 de mayo de 2022). http://dx.doi.org/10.1093/europace/euac053.190.

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Abstract Funding Acknowledgements Type of funding sources: None. Introduction Approximately 18% of patients with atrial fibrillation (AF) undergo a repeat ablation within 12 months after their index ablation. Despite the high prevalence, comparative studies on non-pulmonary vein (PV) target strategies in repeat AF ablation are scarce. Purpose: This study aims to describe 12 months efficacy of non-PV and PV target ablations as a repeat ablation strategy. Methods A multicentre retrospective, descriptive study was conducted with data of 280 patients who underwent repeat AF ablation. Ablation strategy for repeat ablation was at the operators’ discretion. Non-PV target ablation (n=140) included posterior wall isolation, mitral line, roofline and/or complex fractionated atrial electrogram ablation. PV target ablation (n=140), included re-isolation and/or wide atrium circumferential ablation. Patients’ demographics and rhythm outcomes during 12-months follow-up were analysed. Results: Overall, the mean age was 63 ± 9 years, 64% were male, and body mass index was 27.1 ± 4.2. Patients undergoing non-PV target ablation had more frequently persistent AF (47.9% vs 14.3%, p < 0.001), and had a higher CHA2DS2 VASc (2.0 vs 1.3, p < 0.001). At 12 months, more atrial tachyarrhythmias were observed in the non-PV target group (48.6%) compared to the PV target group (29.3%, p=0.001). Similarly, a significantly higher AF and atrial tachycardia (AT) recurrence rate was observed after non-PV target ablation compared to PV target ablation (36.4% versus 22.1% and 22.9% versus 10.7%). After adjusting for several associated covariates, a significantly higher AT recurrence risk remained in the non-PV target group (adjusted OR 2.19 95% CI 1.18 – 4.42, p = 0.023) (Figure 1C). Sensitivity analysis was performed with inverse propensity weighting to assess the robustness of the multivariate model and demonstrated comparable outcomes. Both groups significantly de-escalated anti-arrhythmic drug use, de-escalation was more profound after PV target ablation. Patients with isolated PVs during non-PV target ablation had a significantly higher risk for AF recurrence than those with reconnected PVs (Figure 1B). Conclusion: Compared to PV target ablation, non-PV target repeat ablation did not improve outcomes after 12 months and was independently associated with a higher risk for AT recurrences.

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Mezache, Louisa, Heather Struckman, Anna Phillips, Stephen Baine, Amara Greer-short, Sandor Gyorke, Przemyslaw Radwanski, Thomas J. Hund y Rengasayee Veeraraghavan. "Abstract 13383: The Vascular Endothelial Barrier: A Novel Therapeutic Target for Preventing Atrial Fibrillation". Circulation 142, Suppl_3 (17 de noviembre de 2020). http://dx.doi.org/10.1161/circ.142.suppl_3.13383.

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Atrial fibrillation (AF), the most common arrhythmia, is associated with inflammation and vascular dysfunction. AF patients have elevated levels of vascular endothelial growth factor (VEGF; 90-580 pg/ml), which promotes vascular leak and edema. We have previously identified edema-induced disruption of sodium channel (Na V 1.5) -rich intercalated disk (ID) nanodomains as a novel arrhythmia mechanism. We hypothesized that (i) elevated VEGF levels promote AF by disrupting ID nanodomains, and slowing atrial conduction, and (ii) protection of the vascular barrier can prevent these arrhythmias. Clinically-relevant VEGF levels (500 pg/ml, 60 minutes) increased FITC-dextran extravasation (99.3% vs. 24.3% in vehicle controls) in WT mouse hearts, consistent with increased vascular leak. Electron microscopy revealed ID nanodomain swelling, near both gap junctions (perinexi; 64±9nm vs 17±1nm) and mechanical junctions (63±4nm vs 27±2nm) in VEGF-treated hearts relative to controls. Super-resolution STORM microscopy revealed Na V 1.5 enrichment at perinexi (9±2 fold) and N-cadherin-rich sites (7±1 fold) relative to non-junctional ID sites in control hearts. VEGF reduced Na V 1.5 enrichment at both sites (6±1 and 4±1 fold, respectively), consistent with Na V 1.5 translocation from ID nanodomains. Atrial conduction, assessed by optical mapping, was slowed by VEGF (10±0.4 cm/s vs 21.3±1.3 cm/s at baseline). VEGF increased atrial arrhythmia burden both ex vivo (80% vs 0% in vehicle controls) and in vivo (70% vs 20% in vehicle controls). Next, we tested two strategies shown to prevent vascular barrier breakdown. Blocking connexin43 hemichannels (αCT11 peptide) decreased both incidence (40%) and duration (1.45±3.42s) of VEGF-induced arrhythmias. Likewise, blocking pannexin1 channels (Panx1-IL2 peptide) shortened VEGF-induced arrhythmias (2.48±0.83s). Mefloquine and spironolactone, which are small molecules that respectively inhibit Cx43 hemichannels and pannexin channels, were also found to effectively prevent VEGF-induced atrial arrhythmias. These results highlight VEGF-induced vascular leak as a novel mechanism for AF, and suggest vascular barrier protection as an anti-arrhythmic strategy.

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Chubb, Henry, Kara Motonaga, William R. Goodyer, Anthony Trela, Deb Hanisch, Nicole Boramanand, Erin Lencioni, Mithras Maurille, Anne M. Dubin y Scott R. Ceresnak. "Abstract 11134: The Feasibility of a Mail-Out 12-Lead ECG in a Pediatric Cardiac Electrophysiology Telemedicine Environment". Circulation 144, Suppl_1 (16 de noviembre de 2021). http://dx.doi.org/10.1161/circ.144.suppl_1.11134.

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Introduction: The COVID pandemic has driven an expansion of telemedicine. Telemedicine may be well-suited for pediatric electrophysiology (EP) outpatient consultations. However, an ECG forms part of the standard of care and there is no established strategy for performing a remote 12-lead ECG. Hypothesis: The use of mail-out 12 lead ECG in a pediatric cardiology telemedicine environment is feasible. Methods: Between Nov 2020 and June 2021, select patients with telemedicine EP consultation were offered a mail-out 12 lead ECG (QT Medical, Diamond Bar, CA). The equipment was sent to the patient’s home with technical support from both company and the cardiac clinic. ECGs were read and reported on the electronic health record. ECG quality was independently rated by 2 reviewers. Patient experience was recorded via survey (Qualtrics, Seattle, WA). Results: A total of 146 ECG recordings were transmitted in 31 patients [age 13 ± 5 years, 11 female (35%)]. Indications were prior arrhythmia [24 (77%)] or new cardiac symptoms [7 (23%)]. Prior arrhythmia diagnoses included WPW, paced rhythm, Brugada syndrome, ventricular tachycardia, complete heart block, long QT and monitoring of introduction of anti-arrhythmic medication. A median 3 (IQR 3-6) ECGs were recorded per patient. All patients had recordings suitable for clinical decision-making [21 had an ‘excellent’ recording (68%), 10 ‘good’ (32%), Figure 1]. Total time to perform the ECG (including app set up, application of device and recording transmission) was 46 ± 18 min. 77% found it ‘easy’ or ‘extremely easy’ to perform, and 80% were ‘confident’ or ‘moderately confident’ in the recording. Median travel time to clinic saved was 62 min (IQR 30-151 min). However, only 33% would prefer to perform the ECG at home rather than in clinic Conclusions: Clinically acceptable pediatric 12-lead ECGs may be performed at home by the patient and family. This technology may be considered for adjunctive use with telemedicine consultation in pediatric EP.

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Ding, Jun, Aijuan Cheng, Peng Li, Yingchuan Yan, Yutian Shi, Zuochen Xue, Shan Sun y Jing Xu. "Cryoballoon catheter ablation or drug therapy to delay progression of atrial fibrillation: A single-center randomized trial". Frontiers in Cardiovascular Medicine 9 (19 de octubre de 2022). http://dx.doi.org/10.3389/fcvm.2022.1003305.

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BackgroundDelaying atrial fibrillation (AF) progression is a key goal in cardiovascular treatment. However, numbers of previously published studies on delayed AF progression are relatively limited. The purpose of this study was to determine whether a cryoballoon catheter ablation (CA) strategy could delay AF progression compared to anti-arrhythmic drug (AAD) treatment in patients with paroxysmal AF.MethodsA total of 204 subjects were enrolled in the trial, including 102 in the cryoballoon CA group and 102 in the AAD group. Participants were followed up with for 36 months. The primary study endpoint was the first occurrence of persistent atrial tachyarrhythmia, while secondary endpoints included the event rates of persistent atrial tachyarrhythmia at 1 and 2 years. The primary safety endpoint was serious adverse events.ResultsOverall, the 36-month follow-up was completed by 154 subjects (75.5%). At 3 years, documented progression from paroxysmal AF to persistent atrial tachyarrhythmia had occurred in 2 of the 102 patients assigned to undergo cryoballoon CA [2.203% (95% confidence interval (CI), 0.554–8.537)] and in 17 of the 102 patients assigned to receive AADs [20.223% (95% CI, 13.040–30.604)] [hazard ratio (HR), 0.107; 95% CI, 0.043–0.262; P < 0.001]. Lower rates of progression in the cryoballoon CA group compared to the AAD group were already obvious at 1 year [1.053% (95% CI, 0.149–7.238) vs. 5.284% (95% CI, 2.233–12.237)] [HR, 0.193; (95% CI, 0.039–0.956; P = 0.09)] and 2 years [2.203% (95% CI, 0.554–8.537) vs. 12.430% (95% CI, 7.066–21.371)] (HR, 0.169; 95% CI, 0.057–0.501, P < 0.001). Serious adverse events occurred in 7 of the 102 patients (6.9%) in the cryoballoon CA group and 9 of the 102 patients (8.8%) in the AAD group.ConclusionCryoballoon CA was superior to AAD therapy in preventing the occurrence of persistent atrial tachyarrhythmia in patients with paroxysmal AF who had not received prior rhythm control therapy. Serious adverse events were rare.

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Lankveld, T., S. Zeemering, I. C. Van Gelder, K. E. Odening, H. J. Crijns y U. Schotten. "Dominant frequency predicts sinus rhythm maintenance after electrical cardioversion for persistent atrial fibrillation in men but not in women". European Heart Journal 41, Supplement_2 (1 de noviembre de 2020). http://dx.doi.org/10.1093/ehjci/ehaa946.0542.

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Abstract Background Women are usually underrepresented in studies evaluating rhythm control strategies in patients with atrial fibrillation (AF). Subsequently, the same holds true for studies looking at predictors for success of a rhythm control strategy for AF. Purpose To study the predictive power of the non-invasively determined dominant frequency (DF) on the electrocardiogram (ECG) in men and women undergoing electrical cardioversion (ECV) for persistent AF. Methods We matched 105 female patients undergoing elective ECV for persistent AF and 105 male control patients based on age and cardiovascular comorbidity profile. We determined the DF on all 12 leads of a standard digital 10 seconds ECG recorded on the day of ECV. Recurrences of AF within the first year after ECV were documented. Results There were no differences in comorbidities, AF duration, left ventricular systolic function, indexed left atrial volume and anti-arrhythmic drugs between male and female patients. The dominant frequency was significantly lower in male patients without an AF recurrence on all leads. The best performing lead to identify patients with recurrences was lead III with an AUC 0.752. The optimal cut-off point was a DF <5.98 Hz with a sensitivity 84% and a specificity 67%. There was no significant difference in DF between female patients with and without an AF recurrence. The AUC in lead III was 0.47 (Figure 1). Conclusion The non-invasively measured dominant frequency is able to predict AF recurrence after electrical cardioversion in male patients with persistent AF but not in a matched female cohort. This difference might be explained by different pathophysiological mechanisms underlying AF in male and female patients. Therefore, future research is needed on pathophysiological differences between men and women that can explain and might overcome these challenges. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Network for Translational Research in Atrial Fibrillation (grant no. 261057), the Center for Translational Molecular Medicine (COHFAR),

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Antonelli, Giorgio, Valeria Cammalleri, Valeria Maria De Luca, Ombretta Annibali, Annunziata Nusca, Simona Mega, Myriam Carpenito et al. "957 EMERGING FROM THE DARKNESS. SUDDEN CARDIAC DEATH IN CARDIAC AMYLOIDOSIS". European Heart Journal Supplements 24, Supplement_K (14 de diciembre de 2022). http://dx.doi.org/10.1093/eurheartjsupp/suac121.581.

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Abstract Cardiac amyloidosis (CA) manifests as infiltrative cardiomyopathy with a hypertrophic pattern, usually presenting with heart failure with preserved ejection fraction (HFpEF). In addition, degenerative valvular heart disease, particularly severe aortic stenosis, is commonly seen in patients with CA. However, amyloid fibril deposition may also infiltrate the conduction system and promote the development of electrical disorders, including ventricular tachyarrhythmias (VT), atrio-ventricular block, or acute electromechanical dissociation (EMD). These manifestations can increase the risk of sudden cardiac death (SCD). This review summarizes the pathophysiological mechanisms and risk factors for sudden cardiac death in cardiac amyloidosis and focuses on the major current concerns regarding medical and device management in this challenging scenario. Heart involvement is the major determinant of survival in patient with amyloidosis and a “sudden death” occurs in approximately two-thirds of patients with cardiac amyloidosis. Moreover, the AL amyloid fibrils are shown to be highly cytotoxic to the ventricular myocardial, explaining why ventricular arrhythmias appear more frequently in AL over ATTR. Proposed mechanisms driving electrophysiological manifestations of CA involve intramural coronaries, microvascular ischemia, or patchy myocardium infiltration of amyloid fibrils, causing the development of anatomical re-entrant circuits responsible for ventricular arrhythmia. The prevalence of non-sustained ventricular tachycardia (NSVT) in AL amyloidosis ranges from 5 to 27% with routine monitoring and 100% during the stem cell transplant period. The guidelines don't provide specific indications regarding insertion of implantabile cardioverter defibrillator (ICD) and they don't clarify whether some patients subtypes can benefit from them. Amyloid infiltration into the conduction system enhances the genesis of rhythm disturbances, including fatal ventricular arrhythmias and SCD. Current pharmacological anti-arrhythmic therapies are poorly tolerated in CA, and there are no robust recommendations on the management of ventricular arrhythmias in this subset of patients. Furthermore, the benefit of ICD implantation is highly variable according to the different clinical stages of the disease. Therefore, further studies are needed to create a standardized diagnostic algorithm and appropriate treatment strategy for this special population.

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Dalgaard, F., S. Al-Khatib, J. Pallisgaard, C. Torp-Pedersen, T. B. Lindhardt, G. Gislason y M. Ruwald. "3153Rate versus rhythm control and mortality in atrial fibrillation patients: a Danish nationwide cohort study". European Heart Journal 40, Supplement_1 (1 de octubre de 2019). http://dx.doi.org/10.1093/eurheartj/ehz745.0041.

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Abstract Background Treatment of AF patients with rate or rhythm drug therapy have shown no difference in mortality in clinical trials. However, the generalizability of these trials to real-world populations can be questioned. Purpose We aimed to investigate the all-cause and cardiovascular (CV) mortality risk in a nationwide AF cohort by treatment strategy (rate vs. rhythm) and by individual drug classes. Methods We queried the Danish nationwide registries from 2000 to 2015 to identify patients with AF. A rate control strategy included the use of one or more of the following medications: beta-blocker, digoxin, and a class-4 calcium channel blocker (CCB). A rhythm control strategy included the use of an anti-arrhythmic drug (amiodarone and class-1C). Primary outcome was all-cause mortality. Secondary outcome was CV mortality. Adjusted incidence rate ratios (IRR) were computed using Poisson regression with time-dependent covariates allowing patients to switch treatment during follow-up. Results Of 140,697 AF patients, 131,793 were on rate control therapy and n=8,904 were on rhythm control therapy. At baseline, patients on rhythm control therapy were younger (71 yrs [IQR: 62–78] vs 74 [65–82], p<0.001) more likely male (63.5% vs 51.7% p<0.001), had more prevalent heart failure (31.1% vs 19.4%, p<0.001) and ischemic heart disease (40.1% vs. 23.3%, p<0.001), and had more prior CV-related procedures; PCI (7.4% vs. 4.0% p<0.001) and CABG (15.0% vs. 2.3%, p<0.001). During a median follow up of 4.0 (IQR: 1.7–7.3) years, there were 64,653 (46.0%) deaths from any-cause, of which 27,025 (19.2%) were CVD deaths. After appropriate adjustments and compared to rate control therapy, we found a lower IRR of mortality and CV mortality in those treated with rhythm control therapy (IRR: 0.93 [95% CI: 0.90–0.97] and IRR 0.84 [95% CI: 0.79–0.90]). Compared with beta-blockers, digoxin was associated with increased risk of all-cause and CV mortality (IRR: 1.26 [95% CI: 1.24–1.29] and IRR: 1.32 [95% CI: 1.28–1.36]), so was amiodarone: IRR for all-cause mortality: 1.16 [95% CI: 1.11–1.21] and IRR for CV mortality: 1.12 [95% CI: 1.05–1.19]. Class-1C was associated with lower all-cause (0.43 [95% CI: 0.37–0.49]) and CV mortality (0.35 [95% CI: 0.28–0.44]). Figure 1. Models were adjusted for age, sex, ischemic heart disease, stroke, chronic obstructive pulmonary disease, chronic kidney disease, valvular atrial fibrillation, bleeding, diabetes, ablation, pacemaker, implantable cardioverter defibrillator, hypertension, heart failure, use of loop diuretics, calendar year, and time on treatment. Abbreviations; CCB; calcium channel blocker, PY; person years. Conclusions In a real-world AF cohort, we found that compared with rate control therapy, rhythm control therapy was associated with a lower risk of all-cause and CV mortality. The reduced mortality risk with rhythm therapy could reflect an appropriate patient selection. Acknowledgement/Funding The Danish Heart Foundation

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Griffin, A., A. Thiyagarajah, M. Middeldorp, D. Lau y P. Sanders. "Incidence of new-onset atrial fibrillation after cavotricuspid isthmus ablation for isolated typical atrial flutter: a systematic review and meta-analysis". EP Europace 23, Supplement_3 (1 de mayo de 2021). http://dx.doi.org/10.1093/europace/euab116.266.

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Abstract Funding Acknowledgements Type of funding sources: None. Background There is a lack of consensus guidelines regarding the continuation of anticoagulant therapy following cavotricuspid isthmus (CTI) ablation for typical atrial flutter. This is despite a significant number of patients developing new-onset atrial fibrillation (AF) following the procedure. Furthermore, a summary of Kaplan-Meier estimates for drug-free, arrhythmia-free survival has never been reported. Purpose To estimate the incidence of drug-free, new-onset AF stratified by rhythm monitoring strategy in patients undergoing CTI ablation for isolated typical atrial flutter. Methods PubMed, Embase and MEDLINE databases were searched to identify relevant studies. Only studies where anti-arrhythmic drugs were discontinued post-ablation and that accounted for patient censoring by reporting results in the form of time to event data were included. Data was extracted from published Kaplan-Meier curves using a digitizing software and confidence intervals for the survivor function were estimated based on the number at risk at the time point of interest. Results were pooled in a random effects model using the DerSimonian-Laird estimator. Results Thirteen relevant studies incorporating 1712 patients (79 % male, mean age 63.2 +/-11.2 years, LVEF 55.2 +/-10.8%) were identified. The estimated freedom from new-onset atrial fibrillation was 89.7% (95% CI: 80.3-90.1%) at 1 year and 86.2% (95% CI: 78.4-94.0%) at 2 years in patients undergoing predominantly symptom –based monitoring, 74.6% (95%CI: 67.0-82.3%) at 1 year and 69.5% (95%CI: 63.5-75.6%) at 2 years in patients undergoing regular clinic follow-up with periodic Holter monitoring and 51.4% (95% CI: 41.8-61.0%) at 1 year and 22.7% (95% CI: 8.7% - 36.6%) at 2 years in patients with implantable loop recorders. Conclusion With the advent of implantable loop recorders, it is apparent that most patients with isolated atrial flutter manifest new-onset AF following CTI ablation and the merits of discontinuing anticoagulation must be carefully considered in this population. Symptom-based monitoring likely severely underestimates the incidence of new-onset AF and may lead to adverse outcomes, particularly in patients with a high risk of stroke.

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Khanra, D., A. Mukherjee, S. Deshpande, D. Padmanabhan, S. Mohan, H. Khan, D. Kella y N. Kathuria. "Catheter ablation outscores all other treatment modalities in reducing all-cause mortality and heart failure related morbidity in patients of persistent atrial fibrillation with systolic heart failure". EP Europace 23, Supplement_3 (1 de mayo de 2021). http://dx.doi.org/10.1093/europace/euab116.217.

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Abstract Funding Acknowledgements Type of funding sources: None. Background Catheter ablation in the setting of persistent AF (PeAF) with heart failure (HF) is challenging and often has poor outcome. However, guideline and studies indicate ablation strategy in this group to reduce mortality and HF-related hospitalization. Purpose We have conducted a network meta-analysis (NMA) of all-cause mortality and improvement of HF-related QOL in patients of PeAF with systolic heart failure comparing rate controlling drugs (RCDs), anti-arrhythmic drugs (AAD), catheter ablation (CA) of PeAF and AV nodal ablation with univentricular or biventricular pacing (AVNA). Method Bayesian network meta-analysis of randomized controlled studies comparing mortality and QOL among individual treatment arms (e.g. RCDs, AADs, CA and AVNA) and pair-wise network meta-analysis comparing CA and other treatment arms (RCD, AAD and AVNA) were performed using MetInsight V3. Markov chain Monte Carlo (MCMC) modeling was used to estimate the relative ranking probability of each treatment group. Results Published data of 14 studies including 3698 patients were included in the NMA with a median follow-up of two years (1A, 2A). The Bayesian modelling with MCMC analysis for pair-wise comparison clearly demonstrated that, AAD [OR (95% CrI): 2.10 (0.43-9.0)], AVNA [OR (95% CrI): 1.32 (0.14-11.7)] and RCDs [OR (95% CrI): 2.76 (0.5-14.1)] have higher all-cause mortality than CA but not within the radar of statistical significance (1B). The Bayesian modelling with MCMC analysis for pair-wise comparison clearly demonstrated that, AADs [MD (95% CrI): 8.02 (-8.32-27.8)], AVNA [MD (95% CrI): 17.0 (-1.9-33.1)] and RCDs [MD (95% CrI): 13.0 (0.1-24.5)] have lesser improvement in QOL than CA but not within the radar of statistical significance (2B). Based on the Bayesian model, CA results in lower all-cause mortality and highest improvement of QOL in the patients of AF with HF (3A, 3B). Conclusion This shapes way for future treatment guidelines in patients with PeAF with HF group and points towards CA to be undertaken before medical therapy fails. This also paves way for further research to confirm the longevity of the beneficial effects and to find the specific subsets of AF with HF patients that would be benefited most from CA. Abstract Figure

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Stronati, G., A. Urbinati, M. Alfieri, L. Brugiatelli, F. Maiorino, G. Lombardi, A. Barbarossa et al. "Pure and impure tachycardiomiopathy: key differences and long term prognosis". EP Europace 24, Supplement_1 (18 de mayo de 2022). http://dx.doi.org/10.1093/europace/euac053.136.

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Abstract Funding Acknowledgements Type of funding sources: None. Introduction Tachycardiomioathy (TCM) is a reversible cause of left ventricular (LV) dysfunction, secondary to both atrial and ventricular arrhythmias as well as high burden of ectopic beats. Almost 10% of all hospitalizations for acute heart failure (HF) meet the criteria for TCM. TCM is known to frequently recur and therefore cardiovascular related hospitalizations are often needed. While this is true in pure TCM, long term prognosis of impure TCM is still unknown. Purpose To compare long term prognosis of pure TCM to that of impure TCM in terms of survival rate, time free of recurrence and time free of hospitalizations. Methods Prospective, observational study enrolling all consecutive patients admitted for de novo acute heart failure, with a confirmed diagnosis of TCM, which was suspected in all patients admitted for heart failure (HF) with a LV ejection fraction <50% and concomitant persistent atrial or ventricular arrhythmia, and confirmed after clinical and echocardiographic recovery. Pure tachycardiomiopathy was defined as an arrhythmia-induced LV dysfunction in an otherwise healthy heart. Impure tachycardiomiopathy was defined as an arrhythmia-mediated TCM, where the arrhythmia may exacerbate an underlying condition and facilitate LV dysfunction. Results Population included 123 patients with pure TCM and 40 patients with impure TCM. Patients with pure TCM were significantly younger (68±13 vs. 74±10 years; p=0.008) but a with similar risk factor profile and the same prevalence of male gender (63% vs 72%; p=ns). Similarly, echo characteristics did not significantly differ between the two groups, while pure TCM presented a higher HR at admission (124±28 vs. 106±28 bpm; p=0.001) but not at discharge (70±15 vs. 71±14 bpm; p=ns). Pure and impure TCM had similar EF on admission (33±9 vs. 34±7%; p=ns) and time to recovery after the acute event (4.9±0.6 vs. 4.4±1.4 months; p=ns). Pure TCM were more often treated in the acute phase with a rhythm control strategy (81% vs. 67%; p=0.001), mainly electric cardioversion followed by anti-arrhythmic drugs (80% vs. 46%; p<0.001) and AF ablation (16% vs. 3%; p=0.025). Kaplan Meier curves showed that pure TCM present a lower incidence of recurrence (26% vs. 50%; p=0.05; Figure 1) over a 40-month median follow-up. Cumulative incidences of death (24% vs. 30%; p=ns; Figure 2) and thromboembolism (3% vs. 3%; p=ns) were similar between the two groups over the same period. All-cause hospitalizations were similar between the two groups (62% vs. 67%; p=ns) with the impure TCMs experiencing more unplanned hospitalizations for HF recurrences. Conclusions While pure and impure TCM patients differs in terms of baseline characteristics, they present similar risk of death, thromboembolic events, and hospital admission during a long-term follow-up. Treatment strategy of pure TCM is more often rhythm-oriented and this could explain the lower incidence of HF recurrence.

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Hagiwara, H., M. Watanabe, Y. Fujioka, T. Koya, M. Nakao, Y. Takahashi, R. Kamada, Y. Ohba y T. Anzai. "Suppression of ventricular arrhythmia by mitochondrial calcium uptake via mitochondrial calcium uniporter in the ischemic heart failure mice". European Heart Journal 41, Supplement_2 (1 de noviembre de 2020). http://dx.doi.org/10.1093/ehjci/ehaa946.3699.

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Abstract Background In heart failure (HF), diastolic calcium (Ca) leak from sarcoplasmic reticulum (SR) via ryanodine receptor (RyR) causes delayed after depolarization (DAD), leading ventricular arrhythmias (VAs). Recent study reported that Ca uptake into mitochondria via mitochondrial calcium uniporter (MCU) suppress Ca waves (CaWs) and DAD in catecholaminergic polymorphic ventricular tachycardia, in which diastolic Ca leak is thought to be a major cause of VAs as in HF. However, such anti-arrhythmic effect of mitochondrial Ca uptake via MCU remains unclear in HF. Purpose We sought to investigate whether mitochondrial Ca uptake via MCU decreases CAWs and VAs incidence in ischemic HF mice. Methods Ten-week-old male C57BL/6J mice were divided into 2 groups; sham operation mice (Sham) or HF mice (HF) in which myocardial infarction was induced by left coronary artery ligation. After 4–6 weeks, cardiomyocyte or mitochondria was isolated respectively from the myocardium of Sham and the non-infarct myocardium of HF. Influence of MCU activation on Ca dynamics, VA inducibility and left ventricular hemodynamics were evaluated using Kaemenpferol, a MCU activator. Intracellular Ca dynamics and mitochondrial Ca uptake were measured in isolated cardiomyocytes loaded with Fluo-4 AM on an epifluorescence microscopy and by estimating the extra-mitochondrial Ca reduction with Fluo-5N on a spectrofluoro-photometer, respectively. VAs was induced by programmed stimulation in the Langendorff perfused hearts. Left ventricular (LV) pressure was measured using a microtip transducer catheter. Finally, the effect of intravenous administration of Kaempferol (5mg/kg) on hemodynamic parameters was examined 30 minutes after administration in Sham and HF. Results HF mice showed left ventricular dysfunction, as well as the increased heart and lung weights compared to Sham. MCU protein expression in cardiomyocytes did not differ between Sham and HF. Kaempferol increased mitochondrial Ca uptake in the isolated mitochondria both in Sham and HF. The number of the diastolic CaWs was higher in HF compared to Sham. Such increased number of CaWs in HF was attenuated by 10 μM Kaempferol, which was, however, abolished by a MCU blocker Ruthenium Red. The incidence of induced VA was significantly higher in HF than Sham, which was suppressed by Kaempferol. In vivo measurements, intravenous administration of Kaempferol did not show significant changes in hemodynamic parameters in Sham and HF mice. Conclusions Mitochondrial Ca uptake via MCU suppresses CaWs and VAs, but did not change LV hemodynamics in HF. Whereas traditional antiarrhythmic drugs have limited use in heart failure patients, a novel strategy that promotes Ca uptake into mitochondria might be a new and safer option for treating VAs in HF. Funding Acknowledgement Type of funding source: None

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