Background: Glanzmann thrombasthenia (GT) is a rare bleeding disorder caused by inherited defects of the platelet alpha(IIb)beta(3) integrin. Platelet transfusions can be followed by an immune response that can block integrin function by interfering with fibrinogen binding. Objectives: In this study, we aimed to determine the prevalence of such isoantibodies and better characterize their pathogenic properties. Methods: Twelve patients with GT were evaluated for anti-alpha(IIb)beta(3) isoantibodies. Sera from patients with GT with or without anti-alpha(IIb)beta(3) isoantibodies were then used to study their in vitro effect on platelets from healthy donors. We used several approaches (IgG purification, immunofluorescence staining, and inhibition of signaling pathways) to characterize the pathogenic properties of the anti-alpha(IIb)beta(3) isoantibodies. Results: Only 2 samples were able to severely block integrin function. We observed that these 2 sera caused a reduction in platelet size similar to that observed when platelets become procoagulant. Mixing healthy donor platelets with patients' sera or purified IgGs led to microvesiculation, phosphatidylserine exposure, and induction of calcium influx. This was associated with an increase in procoagulant platelets. Pore formation and calcium entry were associated with complement activation, leading to the constitution of a membrane attack complex (MAC) with enhanced complement protein C5b-9 formation. This process was inhibited by the complement 5 inhibitor eculizumab and reduced by polyvalent human immunoglobulins. Conclusion: Our data suggest that complement activation induced by rare blocking anti-alpha(IIb)beta(3) isoantibodies may lead to the formation of a MAC with subsequent pore formation, resulting in calcium influx and procoagulant platelet phenotype.

Background The benefit–risk balance and optimal timing of surgery for severe infective endocarditis (IE) with ischemic or hemorrhagic strokes is unknown. The study aim was to compare the neurological outcome between patients receiving surgery or not. Methods In a prospective register-based multicenter ICU study, patients were included if they met the following criteria: (i) left-sided IE with an indication for heart surgery; (ii) with cerebral complications documented by cerebral imaging before cardiac surgery; (iii) with Sequential Organ Failure Assessment score ≥ 3. Exclusion criteria were isolated right-sided IE, in-hospital acquired IE and patients with cerebral complications only after cardiac surgery. In the primary analysis, the prognostic value of surgery in term of disability at 6 month was assessed by using a propensity score-adjusted logistic regression. Results 192 patients were included including ischemic stroke (74.5%) and hemorrhagic lesion (15.6%): 67 (35%) had medical treatment and 125 (65%) cardiac surgery. In the propensity score-adjusted logistic regression, a favorable 6-month neurological outcome was associated with surgery (odds ratio 13.8 (95% CI 6.2–33.7). The 1-year mortality was strongly reduced with surgery in the fixed-effect propensity-adjusted Cox model (hazard ratio 0.18; 95% CI 0.11–0.27; p < 0.001). These effects remained whether the patients received delayed surgery ( n = 62/125) or not and whether they were deeply comatose (Glasgow Coma Scale ≤ 10) or not. Conclusions In critically ill IE patients with an indication for surgery and previous cerebral events, a better propensity-adjusted neurological outcome was associated with surgery compared with medical treatment.

This report identifies a novel variant form of the inherited bleeding disorder Glanzmann thrombasthenia, exhibiting only mild bleeding in a physically active individual. The platelets cannot aggregate ex vivo with physiologic agonists of activation, although microfluidic analysis with whole blood displays moderate ex vivo platelet adhesion and aggregation consistent with mild bleeding. Immunocytometry shows reduced expression of & alpha;IIb & beta;3 on quiescent platelets that spontaneously bind/store fibrinogen, and activationdependent antibodies (ligand-induced binding site-319.4 and PAC-1) report & beta;3 extension suggesting an intrinsic activation phenotype. Genetic analysis reveals a single F153S & beta;3 substitution within the & beta;I-domain from a heterozygous T556C nucleotide substitution of ITGB3 exon 4 in conjunction with a previously reported IVS5(+1)G>A splice site mutation with undetectable platelet messenger RNA accounting for hemizygous expression of S153 & beta;3. F153 is completely conserved among & beta;3 of several species and all human & beta;-integrin subunits suggesting that it may play a vital role in integrin structure/function. Mutagenesis of & alpha;IIbF153S & beta;3 also displays reduced levels of a constitutively activated & alpha;IIb-S153 & beta;3 on HEK293T cells. The overall structural analysis suggests that a bulky aromatic, nonpolar amino acid (F,W)153 & beta;3 is critical for maintaining the resting conformation of & alpha;2- and & alpha;1-helices of the & beta;I-domain because small amino acid substitutions (S,A) facilitate an unhindered inward movement of the & alpha;2- and & alpha;1-helices of the & beta;I-domain toward the constitutively active & alpha;IIb & beta;3 conformation, while a bulky aromatic, polar amino acid (Y) hinders such movements and restrains & alpha;IIb & beta;3 activation. The data collectively demonstrate that disruption of F153 & beta;3 can significantly alter normal integrin/platelet function, although reduced expression of & alpha;IIbS153 & beta;3 may be compensated by a hyperactive conformation that promotes viable hemostasis.

BACKGROUND Detailed effects of electrode size on electrograms (EGMs) have not been systematically examined. OBJECTIVES We aimed to elucidate the effect of electrode size on EGMs and investigate an optimal configuration of electrode size and interelectrode spacing for gap detection and far -field reduction. METHODS This study included 8 sheep in which probes with different electrode size and interelectrode spacing were epicardially placed on healthy, fatty, and lesion tissues for measurements. Between 3 electrode sizes (0.1 mm/0.2 mm/0.5 mm) with 3 mm spacing. As indices of capability in gap detection and far -field reduction, in different electrode sizes (0.1 mm/0.2 mm/0.5 mm) and interelectrode spacing (0.1 mm/0.2 mm/0.3 mm/0.5 mm/3 mm) and the optimized electrode size and inter electrode spacing were determined. Compared between PentaRay and the optimal probe determined in study 2. RESULTS Study 1 demonstrated that unipolar voltage and the duration of EGMs increased as the electrode size increased in any tissue (P < .001). Bipolar EGMs had the same tendency in healthy/fat tissues, but not in lesions. Study 2 showed that significantly higher gap to lesion volume ratio and healthy to fat tissue voltage ratio were provided by a smaller electrode (0.2 mm or 0.3 mm electrode) and smaller spacing (0.1 mm spacing), but 0.3 mm electrode/0.1 mm spacing provided a larger bipolar voltage (P < .05). Study 3 demonstrated that 0.3 mm electrode/0.1 mm spacing provided less deflection with more discrete EGMs (P < .0001) with longer and more reproducible AF cycle length (P < .0001) compared to PentaRay. CONCLUSION Electrode size affects both unipolar and bipolar EGMs. Catheters with microelectrodes and very small interelectrode spacing may be superior in gap detection and far -field reduction. Importantly, this electrode configuration could dramatically reduce artifactual complex fractionated atrial electrograms and may open a new era for AF mapping. (C) 2021 Heart Rhythm Society. All rights reserved.

We developed a detailed imaging phenotype of the cerebral complications in critically ill patients with infective endocarditis (IE) and determine whether any specific imaging pattern could impact prognostic information. One hundred ninety-two patients admitted to the intensive care units of seven tertiary centers with severe, definite left IE and neurological complications were included. All underwent cerebral imaging few days after admission to define the types of lesions, their volumes, and their locations using voxel-based lesion-symptom mapping (VLSM). We employed uni- and multi-variate logistic regression analyses to explore the associations among imaging features and other prognostic variables and the 6-month modified Rankin Scale (mRS) score. Ischemic lesions were the most common lesions (75%; mean volume, 15.3 ± 33 mL) followed by microbleeds (50%; mean number, 4 ± 7.5), subarachnoidal hemorrhages (20%), hemorrhagic strokes (16%; mean volume, 14.6 ± 21 mL), and hemorrhagic transformations (10%; mean volume, 5.6 ± 11 mL). The volume of hemorrhagic transformations, the severity of leukopathy, and the compromises of certain locations on the motor pathway from the VLSM were associated with a poor 6-month mRS score on univariate analyses. However, upon multivariate analyses, no such specific imaging pattern independently predicted the mRS; this was instead influenced principally by age (OR = 1.03 [1.004–1.06]) and cardiac surgery status (OR = 0.06 [0.02–0.16]) in the entire cohort, and by age (OR = 1.04 [1.01–1.08]) and Staphylococcus aureus status (OR = 2.86 [1.19–6.89]) in operated patients. In a cohort of severely ill IE patients with neurological complications, no specific imaging pattern could be highlighted as a reliable predictor of prognosis.

BACKGROUND Purkinje ectopics (PurkEs) are major triggers of idiopathic ventricular fibrillation (VF). Identifying clinical factors associated with specific PurkE characteristics could yield insights into the mechanisms of Purkinje-mediated arrhythmogenicity. OBJECTIVE The purpose of this study was to examine the associations of clinical, environmental, and genetic factors with PurkE origin in patients with PurkE-initiated idiopathic VF. METHODS Consecutive patients with PurkE-initiated idiopathic VF from 4 arrhythmia referral centers were included. We evaluated demographic characteristics, medical history, clinical circumstances associated with index VF events, and electrophysiological characteristics of PurkEs. An electrophysiology study was performed in most patients to confirm the Purkinje origin. RESULTS Eighty-three patients were included (mean age 38 +/- 14 years; 44 [53%] women), of whom 32 had a history of syncope. Forty-four patients had VF at rest. PurkEs originated from the right ventricle (RV) in 41 patients (49%), from the left ventricle (LV) in 36 (44%), and from both ventricles in 6 (7%). Seasonal and circadian distributions of VF episodes were similar according to PurkE origin. The clinical characteristics of patients with RV vs LV PurkE origins were similar, except for sex. RV PurkEs were more frequent in men than in women (76% vs 24%), whereas LV and biventricular PurkEs were more frequent in women (81% vs 19% and 83% vs 17%, respectively) (P < .0001). CONCLUSION PurkEs triggering idiopathic VF originate dominantly from the RV in men and from the LV or both ventricles in women, adding to other sex-related arrhythmias such as Brugada syndrome or long QT syndrome. Sex-based factors influencing Purkinje arrhythmogenicity warrant investigation.

Background Conventional bipolar electrodes (CBE) may be suboptimal to detect local abnormal ventricular activities (LAVAs). Microelectrodes (ME) may improve the detection of LAVAs. This study sought to elucidate the detectability of LAVAs using ME compared with CBE in patients with scar-related ventricular tachycardia (VT). Methods We included consecutive patients with structural heart disease who underwent radiofrequency catheter ablation for scar-related VT using either of the following catheters equipped with ME: QDOTTM or IntellaTip MIFITM. Detection field of LAVA potentials were classified as three types: Type 1 (both CBE and ME detected LAVA), Type 2 (CBE did not detect LAVA while ME did), and Type 3 (CBE detected LAVA while ME did not). Results In 16 patients (68 +/- 16 years; 14 males), 260 LAVAs electrograms (QDOT = 72; MIFI = 188) were analyzed. Type 1, type 2, and type 3 detections were 70.8% (QDOT, 69.4%; MIFI, 71.3%), 20.0% (QDOT, 23.6%; MIFI, 18.6%) and 9.2% (QDOT, 6.9%; MIFI, 10.1%), respectively. The LAVAs amplitudes detected by ME were higher than those detected by CBE in both catheters (QDOT: ME 0.79 +/- 0.50 mV vs. CBE 0.41 +/- 0.42 mV, p = .001; MIFI: ME 0.73 +/- 0.64 mV vs. CBE 0.38 +/- 0.36 mV, p < .001). Conclusions ME allow to identify 20% of LAVAs missed by CBE. ME showed higher amplitude LAVAs than CBE. However, 9.2% of LAVAs can still be missed by ME.

HomeCirculation: Arrhythmia and ElectrophysiologyVol. 14, No. 11Catheter Ablation for Atrial Fibrillation in Hyperthyroid Patients Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessLetterPDF/EPUBCatheter Ablation for Atrial Fibrillation in Hyperthyroid Patients Philipp Krisai, MD, Ghassen Cheniti, MD, Tsukasa Kamakura, MD, Takamitsu Takagi, MD, Clémentine André, MD, F. Daniel Ramirez, MD, MSc, Yosuke Nakatani, MD, Takashi Nakashima, MD, Romain Tixier, MD, MSc, Rémi Chauvel, MD, Xavier Pillois, PhD, Josselin Duchateau, MD, PhD, Thomas Pambrun, MD, Nicolas Derval, MD, Frédéric Sacher, MD, PhD, Mélèze Hocini, MD, Michel Haïssaguerre, MD and Pierre Jaïs, MD Philipp KrisaiPhilipp Krisai Correspondence to: Philipp Krisai, MD, Electrophysiology and Ablation Unit, Hospital Haut-Lévêque, Centre hospitalier universitaire de Bordeaux, Av. Magellan, 33600 Pessac, France. Email E-mail Address: [email protected] https://orcid.org/0000-0002-4367-2363 Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France. , Ghassen ChenitiGhassen Cheniti https://orcid.org/0000-0001-7305-311X Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France. , Tsukasa KamakuraTsukasa Kamakura https://orcid.org/0000-0002-3055-7913 Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France. , Takamitsu TakagiTakamitsu Takagi https://orcid.org/0000-0001-6734-0569 Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France. , Clémentine AndréClémentine André Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France. , F. Daniel RamirezF. Daniel Ramirez https://orcid.org/0000-0002-4350-1652 Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France. , Yosuke NakataniYosuke Nakatani https://orcid.org/0000-0002-5427-5048 Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France. , Takashi NakashimaTakashi Nakashima https://orcid.org/0000-0002-8538-9259 Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France. , Romain TixierRomain Tixier https://orcid.org/0000-0003-4093-0483 Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France. , Rémi ChauvelRémi Chauvel Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France. , Xavier PilloisXavier Pillois Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France. , Josselin DuchateauJosselin Duchateau https://orcid.org/0000-0002-4367-1117 Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France. , Thomas PambrunThomas Pambrun Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France. , Nicolas DervalNicolas Derval https://orcid.org/0000-0002-6189-1308 Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France. , Frédéric SacherFrédéric Sacher https://orcid.org/0000-0001-8348-9320 Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France. , Mélèze HociniMélèze Hocini https://orcid.org/0000-0002-7957-8766 Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France. , Michel HaïssaguerreMichel Haïssaguerre https://orcid.org/0000-0001-7644-6146 Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France. and Pierre JaïsPierre Jaïs https://orcid.org/0000-0002-4700-7811 Electrophysiology and Ablation Unit and L'Institut de rythmologie et modélisation cardiaque (LIRYC), Centre hospitalier universitaire de Bordeaux, Bordeaux-Pessac, France. Originally published25 Oct 2021https://doi.org/10.1161/CIRCEP.121.010200Circulation: Arrhythmia and Electrophysiology. 2021;14:e010200Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: October 25, 2021: Ahead of Print The safety and outcome of catheter ablation in hyperthyroid atrial fibrillation (AF) patients is unknown. However, urgent rhythm control may be needed due to severe symptoms or heart failure. We therefore aimed to retrospectively investigate the safety, acute and long-term success of catheter ablation in patients with hyperthyroid AF compared with propensity-score matched, euthyroid controls.Patients were considered overt hyperthyroid if thyroid-stimulating hormone levels were ≤0.4 mUI/L and free thyroxine levels elevated, subclinically hyperthyroid with thyroid-stimulating hormone ≤0.4 mUI/L and normal free thyroxine levels. First procedures consisted of pulmonary vein isolation (PVI) with optional additional lesions (lines, coronary sinus, focal ablation, defragmentation, and ethanol vein of Marshall ablation). Redo-ablation was based on arrhythmia mechanisms and line reconnections. Follow-up included inpatient visits with 24-hour Holter-ECG at 3, 6, and 12 months, referring physician visits at 1 and 9 months and additional 12-lead ECGs in case of symptoms. The primary outcome was documented AF or atrial tachycardia. We propensity-score matched 1:2 (criteria: sex, age, AF-type, first/redo procedure, ablation modality [radiofrequency, cryoablation, or pulsed-field ablation]) with euthyroid controls. The study was approved by the institutional review board, and subjects gave informed consent. The data that support the findings of this study are available from the corresponding author upon reasonable request. Statistical analyses were performed using SPSS V25 and SAS 9.4.In 39 hyperthyroid patients, mean (SD) age was 60.3 (10.6) years, 76.9% were male, and 76.9% had persistent AF. Mean (SD) thyroid-stimulating hormone, T4 and T3 levels were 0.1 (0.1) μUI/mL, 19.0 (7.1) pmol/L, and 5.7 (3.4) pmol/L, respectively. Twenty-four (61.5%) patients were overt, 15 (38.5%) subclinical hyperthyroid. Causes of hyperthyroidism were amiodarone-induced in 31 (79.5%) patients, unknown in 6 (15.4%), and oversubstitution in 2 (5.1%). Three (7.7%) patients showed hyperthyroidism-related symptoms: weight-loss in 2 and insomnia with irritability in 1, the other patients were asymptomatic. The matched cohort was similar in age, sex, AF-type, AF duration, comorbidities, and antiarrhythmic drugs but had a higher left ventricular ejection fraction (58.7% versus 52.3%, P=0.01).It was the first procedure in 43.6%, second in 25.6%, and third or more in 30.8% of the hyperthyroid patients. Radiofrequency was used in 36 (92.3%), cryoballoon in one (2.6%), both radiofrequency and cryoballoon in one (2.6%), and pulsed-field ablation in one (2.6%) patient. Most common ablation targets next to PVI (74.4%) were the cavotricuspid-isthmus (43.6%), left atrial roof (43.6%), and lateral mitral isthmus (35.9%). Acute success with block was achieved for all PVI and cavotricuspid-isthmus lines, in 16/17 (94.1%) left atrial roof lines and in 13/14 (92.9%) mitral isthmus lines. No postprocedural thyrotoxicosis or periprocedural complications, except for one groin hematoma, occurred.The matched cohort showed no differences in the number of procedures, indication for ablation and ablation type compared with the hyperthyroid patients. However, in the euthyroid patients, more PVI (91.0% versus 74.4%, P=0.02), but less left atrial roof lines (16.7% versus 43.6%, P=0.002), coronary sinus ablation (16.7% versus 35.9%, P=0.02), and focal left atrial ablation (5.1% versus 25.6%, P=0.002) were performed. Complications in the matched cohort included 2 pericardial tamponades (managed with percutaneous pericardiocentesis and operative evacuation, respectively), and 1 groin hematoma.Over a mean (SD) follow-up of 10.2 (3.7) months, 18 hyperthyroid patients experienced an AF/atrial tachycardia recurrence: 34.7% at 6 months and 50.8% at 12 months. One patient was lost to follow-up. Compared with the matched cohort with 22 (28.2%) recurrences, the recurrence rate was higher in hyperthyroid patients (P=0.007) (Figure).Download figureDownload PowerPointFigure. Survival curves for the recurrence of atrial fibrillation or atrial tachycardia after catheter ablation in hyperthyroid and propensity score matched, euthyroid patients.Of 36 (92.3%) patients with information on hyperthyroidism treatment, 10 (27.8%) received antithyroid treatment, amiodarone was stopped in all with amiodarone-induced hyperthyroidism, and a watch-and-wait strategy was chosen in 22 (61.1%). Of 30 (76.9%) patients with known subsequent thyroid status, 27 (90%) were euthyroid during follow-up. In the remaining, hyperthyroidism was amiodarone-induced and a watch-and-wait strategy was pursued.Thyroid hormones lead to electrophysiological changes in ion channels and modulate their mRNA expression.1-3 Thereby, the atrial action potential duration and refractory period shorten and render the atria more susceptible for ectopy. These changes are most dominant in the PV but also play an important role inside the atria, suggesting that additional ablation of non-PVI triggers might be beneficial in hyperthyroid patients.2,4 Moreover, data demonstrating prior hyperthyroidism as a predictor of AF-recurrence suggest that these changes may persist after restoration of euthyroidism.4 This is supported by our study: 90% of hyperthyroid patients were euthyroid during follow-up, but still had a higher recurrence rate. Larger studies testing different ablation approaches in hyperthyroid patients are needed to improve outcomes and ascertain safety. Study limitations include the retrospective, nonrandomized design, short follow-up, limited patient number with both overt and subclinical hyperthyroidism, nonuniform hyperthyroidism etiologies (mainly amiodarone-induced), and the inclusion of both first and redo procedures.In conclusion, catheter ablation for AF in hyperthyroid patients was associated with a high acute success rate and no increased risks for periprocedural complications. The long-term success rate was lower compared with euthyroid patients, with 49% of the hyperthyroid patients being arrhythmia free 1 year after ablation.Article InformationSources of FundingDr Krisai is supported by the University of Basel, the Mach-Gaensslen foundation, and the Bangerter-Rhyner foundation. F. Daniel Ramirez is supported by a Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research.DisclosuresNone.FootnotesFor Sources of Funding and Disclosures, see page 1038.Correspondence to: Philipp Krisai, MD, Electrophysiology and Ablation Unit, Hospital Haut-Lévêque, Centre hospitalier universitaire de Bordeaux, Av. Magellan, 33600 Pessac, France. Email philipp.[email protected]chReferences1. Wustmann K, Kucera JP, Zanchi A, Burow A, Stuber T, Chappuis B, Diem P, Delacrétaz E. Activation of electrical triggers of atrial fibrillation in hyperthyroidism.J Clin Endocrinol Metab. 2008; 93:2104–2108. doi: 10.1210/jc.2008-0092CrossrefMedlineGoogle Scholar2. Chen YC, Chen SA, Chen YJ, Chang MS, Chan P, Lin CI. Effects of thyroid hormone on the arrhythmogenic activity of pulmonary vein cardiomyocytes.J Am Coll Cardiol. 2002; 39:366–372. doi: 10.1016/s0735-1097(01)01731-4CrossrefMedlineGoogle Scholar3. Watanabe H, Ma M, Washizuka T, Komura S, Yoshida T, Hosaka Y, Hatada K, Chinushi M, Yamamoto T, Watanabe K, et al.. Thyroid hormone regulates mRNA expression and currents of ion channels in rat atrium.Biochem Biophys Res Commun. 2003; 308:439–444. doi: 10.1016/s0006-291x(03)01420-7CrossrefMedlineGoogle Scholar4. Wongcharoen W, Lin YJ, Chang SL, Lo LW, Hu YF, Chung FP, Chong E, Chao TF, Tuan TC, Chang YT, et al.. History of hyperthyroidism and long-term outcome of catheter ablation of drug-refractory atrial fibrillation.Heart Rhythm. 2015; 12:1956–1962. doi: 10.1016/j.hrthm.2015.06.004CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails November 2021Vol 14, Issue 11Article InformationMetrics © 2021 American Heart Association, Inc.https://doi.org/10.1161/CIRCEP.121.010200PMID: 34693719 Originally publishedOctober 25, 2021 Keywordscatheter ablationatrial fibrillationatrial tachycardiahyperthyroidismoutcomePDF download Advertisement SubjectsArrhythmiasAtrial FibrillationCatheter Ablation and Implantable Cardioverter-Defibrillator

Background: The folded valve is a manual shortening of the Melody device, which has been validated as a valuable therapeutic option for the management of dysfunctional right ventricular outflow tracts needing a short valved stent. In this article, we aimed to evaluate, in a multicenter cohort, the mid-term outcomes of patients in whom a percutaneous pulmonary valve implantation was performed using the folded valve technique. Methods: A 2012 to 2018 retrospective multicenter study was performed in 7 European institutions. All patients who benefit from percutaneous pulmonary valve implantation with a folded Melody valve were included. Results: A total of 49 patients (median age, 19 years [range 4–56], 63% male) were included. The primary percutaneous pulmonary valve implantation indication was right ventricular outflow tract stenosis (n=19; 39%), patched native right ventricular outflow tracts were the most common substrate (n=15; 31%). The folded technique was mostly used in short right ventricular outflow tracts (n=28; 57%). Procedural success was 100%. After a median follow-up of 28 months (range, 4–80), folded Melody valve function was comparable to the immediate postimplantation period (mean transvalvular peak velocity=2.6±0.6 versus 2.4±0.6 m/s, P>0.1; only 2 patients had mild pulmonary regurgitation). Incidence rate of valve-related reinterventions was 2.1% per person per year (95% CI, 0.1%–3.9%). The probability of survival without valve-related reinterventions at 36 months was 90% (95% CI, 76%–100%). Conclusions: The folded Melody valve is a safe technique with favorable mid-term outcomes up to 6.5 years after implantation, comparable with the usual Melody valve implantation procedure. Complications and reinterventions rates were low, making this technique relevant in selected patients.

BACKGROUND Beyond pulmonary vein isolation (PVI), the optimal ablation strategy for persistent atrial fibrillation (AF) remains poorly defined. OBJECTIVE The purpose of this study was to examine a novel comprehensive ablation strategy (Marshall bundle elimination, Pulmonary vein isolation, and Line completion for ANatomical ablation of persistent atrial fibrillation [Marshall-PLAN]) strictly based on anatomical considerations. METHODS Left atrial (LA) sites were sequentially targeted as follows: (1) coronary sinus and vein of Marshall (CS-VOM) musculature; (2) PVI; and (3) anatomical isthmuses (mitral, roof, and cavotricuspid isthmus [CTI]). The primary endpoint was 12-month freedom from AF/atrial tachycardia (AT). RESULTS Seventy-five consecutive patients were included (age 61 +/- 9 years; 10 women; AF duration 9 +/- 11 months; mean LA volume 197 +/- 43 mL). VOM ethanol infusion was completed in 69 patients (92%). The full Marshall-PLAN lesion set (VOM, PVI, mitral, roof, and CTI with block) was successfully completed in 68 patients (91%). At 12 months, 54 of 75 patients (72%) were free from AF/AT after a single procedure (no antiarrhythmic drugs) in the overall cohort. In the subset of patients with a complete Marshall-PLAN lesion set (n = 68), the single procedure success rate was 79%. After 1 or 2 procedures, 67 of 75 patients (89%) remained free from AF/AT (no antiarrhythmic drugs). After 1 or 2 procedures, VOM ethanol infusion was complete in 72 of 75 patients (96%). CONCLUSION A novel ablation strategy that systematically targets anatomical atrial structures (VOM ethanol infusion, PVI, and prespecified linear lesions) is feasible, safe, and associated with a high rate of freedom from arrhythmia recurrence at 12 months in patients with persistent AF.

OBJECTIVES This study systematically evaluated mechanisms of atrial tachycardia (AT) by using ultra-high-resolution mapping in a large cohort of patients. BACKGROUND An incomplete understanding of the mechanism of AT is a major determinant of ablation failure. METHODS Consecutive patients with >= 1 AT (excluding cavotricuspid isthmus-dependent flutter) were included. Mapping was performed with a 64-pole mapping catheter. The AT mechanism was defined based on activation mapping and confirmed by entrainment in selected cases. RESULTS A total of 132 patients were included (60 +/- 12 years; 31 [23%] female; 111 [84%] previous atrial fibrillation [AF] ablation; 5 [4%] previous left atriotomy). One hundred four (94%) of the 111 post-AF ablation AT patients had substrate-based ablation during the index AF ablation. A total of 214 ATs were mapped, with complete definition of the AT mechanism in 206 (96%). A total of 129 (60%) had anatomic macro-re-entry (circuit diameter 44.2 +/- 9.6 mm), 57 (27%) had scar-related localized re-entry (circuit diameter 25.8 +/- 12.2 mm), and 20 (9%) had focal AT. Fifty-eight (45%) patients had multiple ATs (27 [20%] dual-loop re-entry; 60 [43%] sequential AT) with complex and highly variable transitions between AT circuits. A total of 116 (90%) of 129 macro-re-entrant ATs, 56 (98%) of 57 localized AT, and 20 (100%) of 20 focal ATs terminated after radiofrequency ablation. After a mean follow-up of 13 +/- 9 months, 57 (46%) patients experienced recurrence of AT. CONCLUSIONS Among patients with AT in the context of previous atrial interventions, particularly post-AF ablation patients, multiple complex AT circuits are common. Despite complete delineation of arrhythmia circuits using ultra-high-resolution mapping and high acute ablation success rates, long-term freedom from AT is modest. (C) 2020 by the American College of Cardiology Foundation.

AIMS We hypothesized that an epicardial approach using ethanol infusion in the vein of Marshall (EIVOM) may improve the result of ablation for perimitral flutter (PMF). METHODS AND RESULTS  We studied 103 consecutive patients with PMF undergoing high-resolution mapping. The first 71 were treated with radiofrequency (RF) ablation alone (RF-group), and the next 32 underwent EIVOM followed by RF on the endocardial and epicardial mitral isthmus (EIVOM/RF-group). Contact force was not measured during ablation. Acute and 1-year outcomes were compared. Flutter termination rates were similar between the RF-group (63/71, 88.7%) and EIVOM/RF-group (31/32, 96.8%, P = 0.27). Atrial tachycardia (AT) terminated with EIVOM alone in 22/32 (68.6%) in the EIVOM/RF-group. Bidirectional block of mitral isthmus was always achieved in the EIVOM/RF-group, but significantly less frequently achieved in the RF-group (62/71, 87.3%; P = 0.05). Median RF duration for AT termination/conversion was shorter [0 (0-6) s in the EIVOM/RF-group than 312 (55-610) s in the RF-group, P < 0.0001], as well as for mitral isthmus block in the EIVOM/RF-group [246 (0-663) s] than in the RF-group [900 (525-1310) s, P < 0.0001]. Pericardial effusion was observed in 1/32 (3.2%) in EIVOM/RF-group and 5/71 (7.0%) in RF-group (P = 0.66); two in RF-group required drainage and one of them developed subsequent ischaemic stroke. One-year follow-up demonstrated fewer recurrences in the EIVOM/RF-group [6/32 (18.8%)] than in the RF-group [29/71 (40.8%), P = 0.04]. By multivariate analysis, only EIVOM was significantly associated with less AT recurrence (hazard ratio = 0.35, P = 0.018). CONCLUSION Ethanol infusion in the vein of Marshall may reduce RF duration required for PMF termination as well as for mitral isthmus block without severe complications, and the mid-term outcome may be improved by this approach.

BACKGROUND:Morphology algorithms are currently recommended as a standalone discriminator in single-chamber implantable cardioverter defibrillators (ICDs). However, these proprietary algorithms differ in both design and nominal programming.OBJECTIVE:To compare three different algorithms with nominal versus advanced programming in their ability to discriminate between ventricular (VT) and supraventricular tachycardia (SVT).METHODS:In nine European centers, VT and SVTs were collected from Abbott, Boston Scientific, and Medtronic dual- and triple-chamber ICDs via their respective remote monitoring portals. Percentage morphology matches were recorded for selected episodes which were classified as VT or SVT by means of atrioventricular comparison. The sensitivity and related specificity of each manufacturer discriminator was determined at various values of template match percentage from receiving operating characteristics (ROC) curve analysis.RESULTS:A total of 534 episodes were retained for the analysis. In ROC analyses, Abbott Far Field MD (area under the curve [AUC]: 0.91; P < .001) and Boston Scientific RhythmID (AUC: 0.95; P < .001) show higher AUC than Medtronic Wavelet (AUC: 0.81; P < .001) when tested for their ability to discriminate VT from SVT. At nominal % match threshold all devices provided high sensitivity in VT identification, (91%, 100%, and 90%, respectively, for Abbott, Boston Scientific, and Medtronic) but contrasted specificities in SVT discrimination (85%, 41%, and 62%, respectively). Abbott and Medtronic's nominal thresholds were similar to the optimal thresholds. Optimization of the % match threshold improved the Boston Scientific specificity to 79% without compromising the sensitivity.CONCLUSION:Proprietary morphology discriminators show important differences in their ability to discriminate SVT. How much this impact the overall discrimination process remains to be investigated.

Introduction: Persistent atrial fibrillation (PsAF) ablation remains time consuming, even when guided by non-invasive mapping. We investigated the role of a multielectrode irrigated circular radiofrequency (RF) catheter for PsAF ablation. Methods: A circular catheter (nMARQ®, Biosense Webster, Inc) with 10 irrigated simultaneous mapping and ablation electrodes was used in 50 patients with PsAF (age 60 ± 11 years, left atrial (LA) size 21.8 ± 9.7 cm2 and atrial fibrillation (AF) maximum duration 10.6 ± 9.3 months). Ablation was guided by non-invasive mapping (ECUVETM, Cardioinsight Inc.) in 32 (64%) patients. Pulmonary vein isolation (PVI) was systematically performed. Results: After targeting additional non-PV regions including 3 ± 2 indicated by ECVUETM (1-6), AF terminated in 37 (74%) patients, into atrial tachycardia (AT) in 22 and directly into sinus rhythm (SR) in 15 patients. Thirteen patients were in SR during the procedure. PVI required 8.01 ± 5.27 minutes of RF. Eleven patients required direct current (DC) shock to terminate AF. Linear lesions were performed for AT: 14 LA roof lines, 13 mitral isthmus lines and 27 cavo tricuspid isthmus (CTI). Using total of 20.24 ± 17.25 minutes of RF. Interestingly, 5/8 roof line block, 4/5 mitral isthmus line block and 19/24 CTI line block, were blocked with circular catheter only with 5.08 ± 4.58, 3.30 ± 2.56 and 3.26 ± 2.12 minutes of RF duration, respectively. A single tip conventional ablation catheter was required to complete linear lesions and obtain the block in 3 roof lines, 1 mitral isthmus line and 5 CTI. Mean procedure duration was 3.18 ± 1.03 hours. Complications included 1 pericardia effusion managed conservatively and 1 transient ischemic attack (TIA) resolved without any neurological sequelae. One year follow up data was available in 27 (54%) patients, 18 (67%) patients were in SR and 9 (33%) patients had AF recurrence in whom 1 (3%) patient had AT recurrence. Conclusion: Circular radiofrequency ablation catheter demonstrated encouraging results for rapid, safe and effective PsAF ablation when guided by non-invasive phase mapping. The catheter can be used for linear ablations and CTI in addition to PVI, thus obviating the need for an additional ablation catheter in the majority of patients.

BackgroundTo assess the relationship between heart rate response and exercise tolerance in adults with systemic right ventricle (sRV) after atrial switch repair for Transposition of the Great Artery (TGA) in addition to other physiological parameters.MethodsAll patients with a sRV after atrial switch repair for TGA followed in our institution between June 2015 and April 2018 who underwent cardiopulmonary exercise testing (CPET) were analyzed. Cardiac imaging performed within a six-month time period of the CPET were also collected. Chronotropic incompetence was defined as the inability to achieve 80% of age-predicted maximal heart rate reserve (HRR) and <62% on a beta-blocker regimen. Patient characteristics were assessed according to tertiles of the percentage of predicted pVO2 (%ppVO2).ResultsWe studied 70 patients (mean of age 32.4 ± 7.6 years old, 51 males). Mean peak oxygen uptake was 21.5 ± 5.8 mL/kg/min, corresponding to a %ppVO2 of 57 ± 14.1% while mean VE/VCO2 slope was 37.1 ± 8.2. There was a trend toward more exaggerated hyperventilation in patient with lower pVO2. Mean age-adjusted HRR was 68.5 ± 19%. Chronotropic incompetence was observed in 65.7% and was correlated with %ppVO2 (r = 0.482; p < 0.001) as physical training evaluated with Ventilatory Anaerobic threshold (r = 0.571; p < 0.001), while no difference was found based on respiratory parameters. No echocardiographic or Magnetic Resonance Imaging parameters assessing sRV systolic function at rest were correlated with %ppVO2.ConclusionsExercise limitation is related to the inability to increase cardiac output during exercise and is notably due to the degree of chronotropic incompetence.

Essentials Acquired Glanzmann thrombasthenia (GT) is generally caused by anti-αIIb β3 autoantibodies. We report the case of a man with an acquired GT phenotype associated with macrothrombocytopenia. Perturbed platelet function were associated with an activating anti-αIIb β3 IgM autoantibody. This novel clinical entity raises interesting questions about the αIIb β3 integrin signaling. SUMMARY: Background Acquired Glanzmann thrombasthenia (GT) is a bleeding disorder generally caused by anti-αIIb β3 autoantibodies. Objectives We aimed to characterize the molecular mechanism leading to a progressive GT-like phenotype in a patient with chronic immune thrombocytopenia. Patient, Methods, and Results The patient suffered from repeated episodes of gastrointestinal bleeding; further studies indicated a moderate platelet aggregation defect. A few months later, platelet function showed abolished aggregation using all agonists, but normal agglutination with ristocetin. No platelet-bound antibodies were detected, but the presence of large amounts of an IgM type antibody detected together with αIIb β3 in the patient permeabilized platelets suggested that this IgM was an autoantibody causing the internalization of the complex. This was confirmed by the fact that the patient IgM bound to normal platelets but not to platelets from GT type I patients. Moreover, patient's plasma activated αIIb β3 on controls' platelets as evidenced by increased PAC-1 binding. We also demonstrated that the patient plasma triggered αIIb β3 outside-in signaling, as β3 Tyr773 and FAK were phosphorylated, and increased the rate of actin polymerization in resting platelets reflecting an impairment of cytoskeletal reorganization. Because different signs of dysmegakaryopoiesis were also observed in our patient, we evaluated the ability of its serum to impair proplatelets formation and showed that it significantly decreased the number of proplatelet-bearing megakaryocytes in controls' bone marrow stem cells culture compared with normal serum. Conclusions We present the case of a patient with a progressive and severely perturbed platelet function associated with the presence of an IgM activating autoantibody directed against αIIb β3 .

BACKGROUND:Macrothrombocytopenia (MTP) is a rare but enigmatic complication of Glanzmann thrombasthenia (GT), an inherited bleeding disorder caused by the absence of platelet aggregation due to deficiencies of the αIIbβ3 integrin.OBJECTIVES:We report a family with type I GT and a prolonged bleeding time but unusually associated with congenital mild thrombocytopenia and platelet size heterogeneity with giant forms.METHODS AND RESULTS:Sanger sequencing of DNA from the propositus identified 2 heterozygous ITGB3 gene mutations: p.P189S and p.C210S both of which prevent αIIbβ3 expression and are causative of GT but without explaining the presence of enlarged platelets. High-throughput screening led to the detection of a predicted disease-causing heterozygous mutation in the TUBB1 gene: p.G146R, encoding β1-tubulin, a component of the platelet cytoskeleton and a gene where mutations are a known cause of MTP.CONCLUSIONS:Family screening confirmed that this rare phenotype results from oligogenic inheritance while suggesting that the GT phenotype dominates clinically.

Background The natural history and long‐term outcome in pediatric patients with idiopathic ventricular fibrillation (IVF) are poorly characterized. We sought to define the clinical characteristics and long‐term outcomes of a pediatric cohort with an initial diagnosis of IVF. Methods and Results Patients were included from an International Registry of IVF (consisting of 496 patients). Inclusion criteria were: (1) VF with no identifiable cause following comprehensive analysis for ischemic, electrical or structural heart disease and (2) age ≤16 years. These included 54 pediatric IVF cases (age 12.7±3.7 years, 59% male) among whom 28 (52%) had a previous history of syncope (median 2 syncopal episodes [interquartile range 1]). Thirty‐six (67%) had VF in situations associated with high adrenergic tone. During a median 109±12 months of follow‐up, 31 patients (57%) had recurrence of ventricular arrhythmias, mainly VF. Two patients developed phenotypic expression of an inherited arrhythmia syndrome during follow‐up (hypertrophic cardiomyopathy and long QT syndrome, respectively). A total of 15 patients had positive genetic testing for inherited arrhythmia syndromes. Ten patients (18%) experienced device‐related complications. Three patients (6%) died, 2 due to VF storm. Conclusions In pediatric patients with IVF, a minority develop a definite clinical phenotype during long‐term follow‐up. Recurrent VF is common in this patient group.

HomeCirculation: Arrhythmia and ElectrophysiologyVol. 12, No. 6Right Ventricular Electrical Activation in Patients With Repaired Tetralogy of Fallots Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBRight Ventricular Electrical Activation in Patients With Repaired Tetralogy of FallotsInsights From Electroanatomical Mapping and High-Resolution Magnetic Resonance Imaging Zakaria Jalal, MD, PhD, Frédéric Sacher, MD, PhD, Emmanuelle Fournier, MD, Hubert Cochet, MD, PhD, Nicolas Derval, MD, Michel Haissaguerre, MD, PhD, Elvis Teijeira Fernandez, MD, Xavier Iriart, MD, Arnaud Denis, MD, Sylvain Ploux, MD, PhD, Xavier Pillois, PhD, Pierre Bordachar, MD, PhD and Jean-Benoît Thambo, MD, PhD Zakaria JalalZakaria Jalal Zakaria Jalal, MD, PhD, University Hospital of Bordeaux, Ave Magellan, 33600 Pessac, France. Email E-mail Address: [email protected] Department of Pediatric and Adult Congenital Cardiology (Z.J., E.F., X.I., J.B.-T.), Bordeaux University Hospital (CHU), Pessac. IHU Liryc, Electrophysiology and Heart Modeling Institute, Foundation Bordeaux Université, Pessac-Bordeaux (Z.J., F.S., H.C., N.D., M.H., E.T.F., X.I., A.D., S.P., X.P., P.B., J.-B.T.). INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, France (Z.J., F.S., H.C., N.D., M.H., E.T.F., A.D., P.B., J.-B.T.). , Frédéric SacherFrédéric Sacher Electrophysiology and Ablation Unit (F.S., N.D., M.H., A.D., S.P., P.B.), Bordeaux University Hospital (CHU), Pessac. IHU Liryc, Electrophysiology and Heart Modeling Institute, Foundation Bordeaux Université, Pessac-Bordeaux (Z.J., F.S., H.C., N.D., M.H., E.T.F., X.I., A.D., S.P., X.P., P.B., J.-B.T.). INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, France (Z.J., F.S., H.C., N.D., M.H., E.T.F., A.D., P.B., J.-B.T.). , Emmanuelle FournierEmmanuelle Fournier Department of Pediatric and Adult Congenital Cardiology (Z.J., E.F., X.I., J.B.-T.), Bordeaux University Hospital (CHU), Pessac. , Hubert CochetHubert Cochet Department of Radiology (H.C., E.T.F.), Bordeaux University Hospital (CHU), Pessac. IHU Liryc, Electrophysiology and Heart Modeling Institute, Foundation Bordeaux Université, Pessac-Bordeaux (Z.J., F.S., H.C., N.D., M.H., E.T.F., X.I., A.D., S.P., X.P., P.B., J.-B.T.). INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, France (Z.J., F.S., H.C., N.D., M.H., E.T.F., A.D., P.B., J.-B.T.). , Nicolas DervalNicolas Derval Electrophysiology and Ablation Unit (F.S., N.D., M.H., A.D., S.P., P.B.), Bordeaux University Hospital (CHU), Pessac. IHU Liryc, Electrophysiology and Heart Modeling Institute, Foundation Bordeaux Université, Pessac-Bordeaux (Z.J., F.S., H.C., N.D., M.H., E.T.F., X.I., A.D., S.P., X.P., P.B., J.-B.T.). INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, France (Z.J., F.S., H.C., N.D., M.H., E.T.F., A.D., P.B., J.-B.T.). , Michel HaissaguerreMichel Haissaguerre Electrophysiology and Ablation Unit (F.S., N.D., M.H., A.D., S.P., P.B.), Bordeaux University Hospital (CHU), Pessac. IHU Liryc, Electrophysiology and Heart Modeling Institute, Foundation Bordeaux Université, Pessac-Bordeaux (Z.J., F.S., H.C., N.D., M.H., E.T.F., X.I., A.D., S.P., X.P., P.B., J.-B.T.). INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, France (Z.J., F.S., H.C., N.D., M.H., E.T.F., A.D., P.B., J.-B.T.). , Elvis Teijeira FernandezElvis Teijeira Fernandez Department of Radiology (H.C., E.T.F.), Bordeaux University Hospital (CHU), Pessac. IHU Liryc, Electrophysiology and Heart Modeling Institute, Foundation Bordeaux Université, Pessac-Bordeaux (Z.J., F.S., H.C., N.D., M.H., E.T.F., X.I., A.D., S.P., X.P., P.B., J.-B.T.). INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, France (Z.J., F.S., H.C., N.D., M.H., E.T.F., A.D., P.B., J.-B.T.). , Xavier IriartXavier Iriart Department of Pediatric and Adult Congenital Cardiology (Z.J., E.F., X.I., J.B.-T.), Bordeaux University Hospital (CHU), Pessac. IHU Liryc, Electrophysiology and Heart Modeling Institute, Foundation Bordeaux Université, Pessac-Bordeaux (Z.J., F.S., H.C., N.D., M.H., E.T.F., X.I., A.D., S.P., X.P., P.B., J.-B.T.). , Arnaud DenisArnaud Denis Electrophysiology and Ablation Unit (F.S., N.D., M.H., A.D., S.P., P.B.), Bordeaux University Hospital (CHU), Pessac. IHU Liryc, Electrophysiology and Heart Modeling Institute, Foundation Bordeaux Université, Pessac-Bordeaux (Z.J., F.S., H.C., N.D., M.H., E.T.F., X.I., A.D., S.P., X.P., P.B., J.-B.T.). INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, France (Z.J., F.S., H.C., N.D., M.H., E.T.F., A.D., P.B., J.-B.T.). , Sylvain PlouxSylvain Ploux Electrophysiology and Ablation Unit (F.S., N.D., M.H., A.D., S.P., P.B.), Bordeaux University Hospital (CHU), Pessac. IHU Liryc, Electrophysiology and Heart Modeling Institute, Foundation Bordeaux Université, Pessac-Bordeaux (Z.J., F.S., H.C., N.D., M.H., E.T.F., X.I., A.D., S.P., X.P., P.B., J.-B.T.). , Xavier PilloisXavier Pillois IHU Liryc, Electrophysiology and Heart Modeling Institute, Foundation Bordeaux Université, Pessac-Bordeaux (Z.J., F.S., H.C., N.D., M.H., E.T.F., X.I., A.D., S.P., X.P., P.B., J.-B.T.). , Pierre BordacharPierre Bordachar Electrophysiology and Ablation Unit (F.S., N.D., M.H., A.D., S.P., P.B.), Bordeaux University Hospital (CHU), Pessac. IHU Liryc, Electrophysiology and Heart Modeling Institute, Foundation Bordeaux Université, Pessac-Bordeaux (Z.J., F.S., H.C., N.D., M.H., E.T.F., X.I., A.D., S.P., X.P., P.B., J.-B.T.). INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, France (Z.J., F.S., H.C., N.D., M.H., E.T.F., A.D., P.B., J.-B.T.). and Jean-Benoît ThamboJean-Benoît Thambo Department of Pediatric and Adult Congenital Cardiology (Z.J., E.F., X.I., J.B.-T.), Bordeaux University Hospital (CHU), Pessac. IHU Liryc, Electrophysiology and Heart Modeling Institute, Foundation Bordeaux Université, Pessac-Bordeaux (Z.J., F.S., H.C., N.D., M.H., E.T.F., X.I., A.D., S.P., X.P., P.B., J.-B.T.). INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, France (Z.J., F.S., H.C., N.D., M.H., E.T.F., A.D., P.B., J.-B.T.). Originally published22 May 2019https://doi.org/10.1161/CIRCEP.119.007141Circulation: Arrhythmia and Electrophysiology. 2019;12:e007141Surgical repair of tetralogy of Fallot almost universally induces a right bundle branch block (RBBB). The noninvasive assessment of right ventricular (RV) activation, using ECG or transthoracic echocardiography, has become a mainstay in the follow-up of these patients because QRS duration has been identified as a predictor of sudden death, ventricular arrhythmias, or hemodynamic impairment.1 Although the origin of this RBBB is mainly related to surgical lesions of the conduction pathways, its evolutive course is seemingly associated with infundibular or global RV remodeling and fibrosis.2,3 In this setting, this prospective study aimed to (1) characterize RV electrical activation in patients with repair of tetralogy of Fallot with hemodynamic and arrhythmic complications using endocardial electroanatomical mapping and (2) study the anatomical, surgical, and ventricular volumetric features associated with RV activation.Consecutive repair of tetralogy of Fallot patients referred for endocardial electrophysiological study (EPS) were included prospectively between 2011 and 2016. Indications for electrophysiological study were as follows: (1) symptomatic arrhythmia and (2) pulmonary valve dysfunction requiring valve replacement (pulmonary valve replacement). An 8F ablation catheter (Navi-Star, Biosense Webster) was inserted under conscious sedation through the femoral vein up to the RV allowing the generation of electroanatomical voltage maps followed by programmed ventricular pacing.3 RV activation maps were constructed from the same recordings, on which the following data were analyzed: (1) RV activation delay, measured between the onset of surface QRS serving as reference and the first endocardial RV activation; (2) RV apical activation (measured between the first RV activation and the first electrogram activated in the apex); (3) RV activation duration (RVAD) measured between the first and the last RV endocardial activation (excluding low-voltage peri-scar zones [<0.5 mV] with fragmented electrograms on which the measurements were not reproducible); and (4) RV activation pattern defined as the activation sequence of the following 4 RV regions: septum, apex, anterior free wall, and the infundibulum.In addition, the patients underwent a standardized protocol including 12-lead ECG and 1.5T magnetic resonance imaging (Aera, Siemens Medical Systems, Erlangen, Germany) assessing ventricular volumetry, function, and fibrosis using high spatial resolution sequences (Figure [A] through [C]). Data are presented as median (interquartile range) or number (percentage). Comparisons between the quantitative variables of the different subgroups were performed using the Student t test when n≥20 and the Mann-Whitney test if n<20. For nominal variables, a χ2 test was used if n≥5 in all groups and Fisher exact test if at least 1 group had n<5. A linear regression test was used for correlation analyses. A probability P<0.05 was considered significant. Data analysis was performed using the STATA software (StataCorpLP, College Station, TX). The study protocol was approved by the local ethics committee. A written consent was signed by all patients. The data that support the findings of this study are available from the corresponding author on reasonable request.Download figureDownload PowerPointFigure. Magnetic resonance imaging (MRI)–based fibrosis analysis in a patient admitted for pulmonary valve replacement. On high spatial resolution late gadolinium enhancement images (A), a subendocardial contour is drawn (B). The intensity of the parietal enhancement is thresholded, with only those pixels with an intensity >50% of the maximum being considered as cicatricial. The septal and infundibular scar areas are measured on a surface map of the enhancements over the entire right ventricular (RV; C). D–G, Electroanatomical RV voltage and activation mapping of a 30-year-old patient admitted for before pulmonary valve replacement. Anterior (D and E) and posterior (F and G) views of the RV. D and F, RV activation maps: electrical activation emerges at the mid portion of the interventricular septum (in red) and propagates toward the apex followed by the infundibulum before ending in the anterior free wall. E and G, RV voltage maps: low-voltage areas (red) correspond to surgical scars at the level of the ventricular septum defect (VSD) and infundibular patches. When analyzing the activation pattern as a function of the surgical scars substrate, we can observe that the septal activation breakthrough is followed by 2 spreads of activation: (1) toward the basal septum which undergoes a conduction block (* in F) in an area which corresponds to the VSD patch on the corresponding voltage map (G) and (2) toward the apex followed by the anterior free wall. This propagation wave (F) appears to bypass the infundibular scar visible on the corresponding voltage map (E). IVS indicates interventricular septum; PA, pulmonary artery; RVOT, right ventricular outflow tract; and TA, tricuspid annulus.Fifty-six consecutive patients were included (median age 29 years [23–45], male n=40 [71.4%], right ventriculotomy n=56 [100%]) as part of a preoperative pulmonary valve replacement assessment (n=36) and for ablation (n=20). Complete RBBB was present in 90.6% (n=48) of cases (median QRS duration 159 ms [140–171], 9 patients [17%] had QRS ≥180 ms, and 27 [51%] had QRS ≥160 ms).Median magnetic resonance imaging–indexed RV end-diastolic volume and end-systolic volume were 152 mL/m2 (135–175.5) and 105 mL/m2 (96–127), respectively. Quantitative analysis of myocardial fibrosis was available in 37 patients (72.5%). The median total RV, RV septal scar, and RV infundibular fibrotic surface areas were 18.9 cm2 (14.2–24.6); 6.7 cm2 (4.6–9); and 10.8 cm2 (7.8–14.9), respectively. Total RV and infundibular fibrotic areas were significantly increased in patients with a QRS ≥180 ms (31.1 versus 15.5 cm2; P=0.007 and 18 versus10 cm2; P=0.017, respectively).Endocardial mapping showed a median RV activation delay of 21 ms (8–35) and a prolonged RVAD of 134 ms (118–157). Median apical activation time was 30 ms (0–56); 16 patients (28.5%) had central RBBB (apical activation time >40 ms), whereas the remaining patients (n=40, 71.5%) had peripheral RBBB.4 Patients with a QRS≥180 ms and RV end-diastolic volume ≥150 mL/m2 had a significantly longer RVAD (155 ms versus 131 ms; P=0.0013 and 143 ms versus 126 ms; P=0.034, respectively). The linear correlations with RVAD were weak albeit significant with regard to QRS duration (r=0.44; P<0.001)5 and RV end-diastolic volume (r=0.32; P<0.05).The RV activation sequence found in the majority of patients was as follows: a single breakthrough located in the interventricular septum (80.4%), then frontwave propagation toward the apex (69.6%), followed by the infundibulum (67.9%). The latest region was the free wall (76.8%) or the infundibulum (19.6%; Figure [D] through [G]). Patients whose infundibulum was the latest activated region had a significantly longer RVAD (164 ms versus 130.5 ms; P=0.001). When superimposing voltage and activation maps, surgical scars were found to impact the electrical activation according to 2 pathways (Figure [D] through [G]):The propagation of the activation originating from the basal septum incurred a conduction block at the basal portion of the interventricular septum in an area corresponding to the VSD patch on voltage maps.The impulse propagating on the RV anterior wall appeared to bypass the ventriculotomy scars and infundibular/transannular patches.To our knowledge, this is the largest cohort including repair of tetralogy of Fallot patients with arrhythmic and valvular complications in whom RV activation was assessed invasively. In conclusion, we showed that (1) there was a predominant activation sequence ending in the RV free wall in a majority of patients, (2) the RV activation was significantly prolonged in the whole RV including areas free from scars, due in particular to anatomic factors and to RV dilatation, and (3) surface QRS duration only partially reflects RV activation process. Additional studies focusing on ventricular electromechanical coupling and involving LV activation are needed to improve our understanding of the underlying mechanisms leading to long-term complications in these patients.Sources of FundingThis study received financial support from the French Government as part of the "Investments of the future" program managed by the National Research Agency (ANR), Grant reference ANR-10-IAHU-04.DisclosuresDr Sacher received speaking honoraria from Biosense Webster. The other authors report no conflicts.Footnotes*Drs Bordachar and Thambo contributed equally to this work.Zakaria Jalal, MD, PhD, University Hospital of Bordeaux, Ave Magellan, 33600 Pessac, France. Email [email protected]comReferences1. Gatzoulis MA, Till JA, Somerville J, Redington AN. Mechanoelectrical interaction in tetralogy of Fallot. QRS prolongation relates to right ventricular size and predicts malignant ventricular arrhythmias and sudden death.Circulation. 1995; 92:231–237.LinkGoogle Scholar2. Horowitz LN, Alexander JA, Edmunds LH. Postoperative right bundle branch block: identification of three levels of block.Circulation. 1980; 62:319–328.LinkGoogle Scholar3. Uebing A, Gibson DG, Babu-Narayan SV, Diller GP, Dimopoulos K, Goktekin O, Spence MS, Andersen K, Henein MY, Gatzoulis MA, Li W. 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June 2019Vol 12, Issue 6 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/CIRCEP.119.007141PMID: 31113235 Originally publishedMay 22, 2019 Keywordsechocardiographyarrhythmiahemodynamicelectrophysiologytetralogy of FallotPDF download Advertisement SubjectsCongenital Heart DiseaseElectrophysiology

OBJECTIVES This study sought to evaluate the relation between bipolar electrode spacing and far- and near-field electrograms. BACKGROUND The detailed effects of bipolar spacing on electrograms (EGMs) is not well described. METHODS With a HD-Grid catheter, EGMs from different bipole pairs could be created in each acquisition. This study analyzed the effect of bipolar spacing on EGMs in 7 infarcted sheep. A segment was defined as a 2-mm center-to-center bipole. In total, 4,768 segments (2,020 healthy, 1,542 scar, and 1,206 in border areas, as defined by magnetic resonance imaging [MRI]) were covered with an electrode pair of spacing of 2 mm (Bi-2), 4 mm (Bi-4), and 8 mm (Bi-8). RESULTS A total of 3,591 segments in Bi-2 were free from local abnormal ventricular activities (LAVAs); 1,630 segments were within the MRI-defined scar and/or border area. Among them, 172 (10.6%) segments in Bi-4 and 219 (13.4%) segments in Bi-8 showed LAVAs. In contrast, LAVAs were identified in 1,177 segments in Bi-2; 1,118 segments were within the MRI-defined scar and/or border area. Among them, LAVAs were missed in 161 (14.4%) segments in Bi-4 and in 409 (36.6%) segments in Bi-8. In segments with LAVAs, median far-field voltage increased from 0.09 mV (25th to 75th percentile: 0.06 to 0.14 mV) in Bi-2, to 0.16 mV (25th to 75th percentile: 0.10 to 0.24 mV) in Bi-4, and to 0.28 mV (25th to 75th percentile: 0.20 to 0.42 mV) in Bi-8 (p < 0.0001). Median near-field voltage increased from 0.14 mV (25th to 75th percentile: 0.08 to 0.25 mV) in Bi-2, to 0.21 mV (25th to 75th percentile: 0.12 to 0.35 mV) in Bi-4, and to 0.32 mV (25th to 75th percentile: 0.17 to 0.48 mV) in Bi-8 (p < 0.0001). The median near-/far-field voltage ratio decreased from 1.67 in Bi-2, to 1.43 in Bi-4, and 1.23 in Bi-8 (p < 0.0001). CONCLUSIONS Closer spacing better discriminates surviving tissue from dead scar area. Although far-field voltage systematically increases with spacing, near-field voltages were more variable, depending on local surviving muscular bundles. Near-field EGMs are more easily observed with smaller spacing, largely due to the reduction of the far-field effect. (C) 2019 by the American College of Cardiology Foundation.