BACKGROUND SCN5A variants are associated with a spectrum of cardiac electrical disorders with clear phenotypes. However, they may also be associated with complex phenotypic traits like overlap syndromes or pleiotropy, which have not been systematically described. In addition, the involvement of SCN5A in dilated cardiomyopathies (DCMs) remains controversial. OBJECTIVE We aimed to evaluate the different phenotypes associated with pathogenic (P)/likely pathogenic (LP) SCN5A variants and to determine the prevalence of pleiotropy in a large multicentric cohort of P/LP SCN5A variant carriers. METHODS The DNA of 13,510 consecutive probands (9960 with cardiomyopathies) was sequenced with a custom panel of genes. Individuals carrying a heterozygous single P/LP SCN5A variant were selected and phenotyped. RESULTS The study included 170 P/LP variants found in 495 patients. Of them, 119 (70%) were exclusively associated with a single well-established phenotype: 91 with Brugada syndrome, 15 with type 3 long QT syndrome, 6 with progressive cardiac conduction disease, 4 with multifocal ectopic Purkinje-related premature contractions, and 3 with sick sinus syndrome. Thirtytwo variants (19%) were associated with overlap syndromes or pleiotropy. The 19 remaining variants (11%) were associated with atypical or unclear phenotypes. Of those, 8 were carried by 8 patients presenting with DCM with a debatable causative genotype/phenotype link. CONCLUSION Most P/LP SCN5A variants were found in patients with primary electrical disorders, mainly Brugada syndrome. Nearly 20% were associated with overlap syndromes or pleiotropy, underscoring the need for comprehensive phenotypic evaluation. The concept of SCN5A variants causing DCM is extremely rare (8/9960) if not questionable.

AbstractAimsLittle is known about patients with right bundle branch block (RBBB)-ventricular tachycardia (VT) and arrhythmogenic cardiomyopathy (ACM). Our aims were: (i) to describe electrocardiogram (ECG) characteristics of sinus rhythm (SR) and VT; (ii) to correlate SR with RBBB-VT ECGs; and (iii) to compare VT ECGs with electro-anatomic mapping (EAM) data.Methods and resultsFrom the European Survey on ACM, 70 patients with spontaneous RBBB-VT were included. Putative left ventricular (LV) sites of origin (SOOs) were estimated with a VT-axis-derived methodology and confirmed by EAM data when available. Overall, 49 (70%) patients met definite Task Force Criteria. Low QRS voltage predominated in lateral leads (n = 37, 55%), but QRS fragmentation was more frequent in inferior leads (n = 15, 23%). T-wave inversion (TWI) was equally frequent in inferior (n = 28, 42%) and lateral (n = 27, 40%) leads. TWI in inferior leads was associated with reduced LV ejection fraction (LVEF; 46 ± 10 vs. 53 ± 8, P = 0.02). Regarding SOOs, the inferior wall harboured 31 (46%) SOOs, followed by the lateral wall (n = 17, 25%), the anterior wall (n = 15, 22%), and the septum (n = 4, 6%). EAM data were available for 16 patients and showed good concordance with the putative SOOs. In all patients with superior-axis RBBB-VT who underwent endo-epicardial VT activation mapping, VT originated from the LV.ConclusionsIn patients with ACM and RBBB-VT, RBBB-VTs originated mainly from the inferior and lateral LV walls. SR depolarization and repolarization abnormalities were frequent and associated with underlying variants.

HomeCirculation: Genomic and Precision MedicineVol. 16, No. 3Phenotypic Characterization of Timothy Syndrome Caused by the CACNA1C p.Gly402Ser Variant No AccessResearch ArticleRequest AccessFull TextAboutView Full TextView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toNo AccessResearch ArticleRequest AccessFull TextPhenotypic Characterization of Timothy Syndrome Caused by the CACNA1C p.Gly402Ser Variant Antoine Delinière, Christelle Haddad, Claudia Herrera-Siklódy, Alexis Hermida, Etienne Pruvot, Sabrina Bressieux-Degueldre, Gilles Millat, Alexandre Janin, Jean-Sylvain Hermida, Babken Asatryan and Philippe Chevalier Antoine DelinièreAntoine Delinière https://orcid.org/0000-0002-3742-9674 National Reference Center for Inherited Arrhythmias of Lyon, Department of Cardiac Electrophysiology, Hôpital Cardiologique Louis Pradel, Hospices Civils de Lyon (HCL), Lyon, France (A.D., C.H., P.C.). University of Lyon, Claude Bernard Lyon 1 University, MeLiS, CNRS UMR 5284, INSERM U1314, Institut NeuroMyoGène, Lyon, France (A.D., P.C.). , Christelle HaddadChristelle Haddad National Reference Center for Inherited Arrhythmias of Lyon, Department of Cardiac Electrophysiology, Hôpital Cardiologique Louis Pradel, Hospices Civils de Lyon (HCL), Lyon, France (A.D., C.H., P.C.). , Claudia Herrera-SiklódyClaudia Herrera-Siklódy https://orcid.org/0000-0001-6881-3073 Arrhythmia Unit, Department of Cardiology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland (C.H.-S., E.P.). , Alexis HermidaAlexis Hermida https://orcid.org/0000-0003-2392-3759 Cardiology, Arrhythmia, and Cardiac Stimulation Service, Amiens-Picardie University Hospital, Amiens, France (A.H., J.-S.H.). , Etienne PruvotEtienne Pruvot https://orcid.org/0000-0003-1386-9285 Arrhythmia Unit, Department of Cardiology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland (C.H.-S., E.P.). , Sabrina Bressieux-DegueldreSabrina Bressieux-Degueldre https://orcid.org/0000-0001-5011-1495 Pediatric Cardiology Unit, Woman-Mother-Child Department, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland (S.B.-D.). , Gilles MillatGilles Millat https://orcid.org/0000-0001-6127-0694 Cardiogenetic laboratory, Centre de biologie et pathologie Est, Hospices Civils de Lyon (HCL), Lyon, France (G.M., A.J.). , Alexandre JaninAlexandre Janin https://orcid.org/0000-0003-3571-003X Cardiogenetic laboratory, Centre de biologie et pathologie Est, Hospices Civils de Lyon (HCL), Lyon, France (G.M., A.J.). , Jean-Sylvain HermidaJean-Sylvain Hermida https://orcid.org/0000-0001-9276-2886 Cardiology, Arrhythmia, and Cardiac Stimulation Service, Amiens-Picardie University Hospital, Amiens, France (A.H., J.-S.H.). , Babken AsatryanBabken Asatryan https://orcid.org/0000-0002-0050-5717 Department of Cardiology, Inselspital, Bern University Hospital, Bern, Switzerland (B.A.). and Philippe ChevalierPhilippe Chevalier Correspondence to: Philippe Chevalier, MD, PhD, Department of Rhythmology, Louis Pradel Cardiovascular Hospital, 26 Avenue du Doyen Jean Lépine 69500 Bron, France. Email E-mail Address: [email protected] https://orcid.org/0000-0001-8185-2229 National Reference Center for Inherited Arrhythmias of Lyon, Department of Cardiac Electrophysiology, Hôpital Cardiologique Louis Pradel, Hospices Civils de Lyon (HCL), Lyon, France (A.D., C.H., P.C.). University of Lyon, Claude Bernard Lyon 1 University, MeLiS, CNRS UMR 5284, INSERM U1314, Institut NeuroMyoGène, Lyon, France (A.D., P.C.). Originally published3 Apr 2023https://doi.org/10.1161/CIRCGEN.122.004010Circulation: Genomic and Precision Medicine. 2023;16:280–282FootnotesFor Sources of Funding and Disclosures, see page 281.Circulation: Genomic and Precision Medicine is available at www.ahajournals.org/journal/circgenCorrespondence to: Philippe Chevalier, MD, PhD, Department of Rhythmology, Louis Pradel Cardiovascular Hospital, 26 Avenue du Doyen Jean Lépine 69500 Bron, France. Email philippe.[email protected].frReferences1. Reichenbach H, Meister EM, Theile H. The heart-hand syndrome. A new variant of disorders of heart conduction and syndactylia including osseous changes in hands and feet.Kinderarztl Prax. 1992; 60:54–56. PMID: 1318983MedlineGoogle Scholar2. Walsh MA, Turner C, Timothy KW, Seller N, Hares DL, James AF, Hancox JC, Uzun O, Boyce D, Stuart AG, et al. A multicentre study of patients with Timothy syndrome.Europace. 2018; 20:377–385. doi: 10.1093/europace/euw433CrossrefMedlineGoogle Scholar3. Splawski I, Timothy KW, Decher N, Kumar P, Sachse FB, Beggs AH, Sanguinetti MC, Keating MT. Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations.Proc Natl Acad Sci U S A. 2005; 102:8089–8096; discussion 8086. doi: 10.1073/pnas.0502506102CrossrefMedlineGoogle Scholar4. Giudicessi JR, Ackerman MJ. Calcium revisited: new insights into the molecular basis of long-QT syndrome.Circ Arrhythm Electrophysiol. 2016; 9:002480. doi: 10.1161/CIRCEP.116.002480LinkGoogle Scholar5. Hermida A, Jedraszak G, Kubala M, Bourgain M, Bodeau S, Hermida J-S. Use of ranolazine as rescue therapy in a patient with Timothy syndrome type 2.Rev Esp Cardiol (Engl Ed). 2022; 75:447–448. doi: 10.1016/j.rec.2021.11.003CrossrefMedlineGoogle Scholar eLetters(0)eLetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.Comments and feedback on AHA/ASA Scientific Statements and Guidelines should be directed to the AHA/ASA Manuscript Oversight Committee via its Correspondence page.Sign In to Submit a Response to This Article Previous Back to top Next FiguresReferencesRelatedDetails June 2023Vol 16, Issue 3 Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/CIRCGEN.122.004010PMID: 37009738 Originally publishedApril 3, 2023 Keywordsatrioventricular blockventricular fibrillationTimothy syndromesudden deathmexiletineranolazinelong QT syndromePDF download Advertisement SubjectsGeneticsSudden Cardiac DeathVentricular Fibrillation

BACKGROUND Sodium channel Mocker (SCB) infusion is used to unmask the electrocardiographic pattern of Brugada syndrome. The test may also induce premature ventricular complexes (PVCs) in individuals without Brugada pattern, the clinical relevance of which is little known. OBJECTIVE The purpose of this study was to describe the prevalence of short-coupled (Sc) PVCs induced by ajmaline or flecainide in patients with suspected or documented severe ventricular arrhythmias. METHODS We reviewed the SCB tests performed in 335 patients with suspected ventricular arrhythmias and structurally normal hearts in 9 centers. ScPVCs were defined as frequent and repetitive PVCs with an R-on-T pattern on SCB tests. Repeated SCB tests were performed in 7 patients and electrophysiological mapping of ScPVCs in 9. RESULTS Sixteen patients (8 men; mean age 36 +/- 11 years) showed ScPVCs and were included. ScPVCs appeared 229 +/- 118 seconds after the initiation of infusion and displayed coupling intervals of 288 +/- 28 ms. ScPVC patterns were monomorphic in 12 patients, originating from the Purkinje system in mapped patients. Repetitive PVCs were induced in 15 patients (94%) including polymorphic ventricular tachycardias in 9 (56%). SCB infusion was repeated 45 (interquartile range 0.6-46) months later and induced identical ScPVC in all. SCB test was the only mean to reveal the malignant arrhythmia in 6 patients. Catheter ablation was performed in 9 patients, resulting in arrhythmia elimination in 8 with a follow-up of 6 (interquartile range 2-9) years. CONCLUSION SCB can induce ScPVC, mostly from Purkinje tissue, in a small subset of patients with idiopathic ventricular arrhythmias. Its high reproducibility suggests a distinct individual mechanism.

BACKGROUND:There is no consensus on the most effective radiofrequency ablation strategy for the initial or repeated treatment of persistent atrial tachyarrhythmia (ATa). OBJECTIVE:To describe success and complication rates after the creation of left atrial (LA) linear lesions for recurrent persistent ATa following an index cryoballoon pulmonary vein isolation (PVI), and to identify predictors of ATa recurrence. METHODS:During March 2013 to March 2020, we prospectively included all consecutive patients undergoing repeat procedures for the treatment of persistent ATa. Radiofrequency ablation consisting of the creation of linear lesions: a roofline, a mitral isthmus and/or septal line, and a cavotricuspid isthmus line. All patients were prospectively followed up for ATa recurrence. RESULTS:Overall, 133 patients underwent 170 procedures after initial cryoballoon PVI (n=715). At least one pulmonary vein reconnection was observed in 60 patients (45.1%), all of whom underwent successful re-disconnection. After all the procedures, >90% of patients had a lesion pattern consisting of a roofline, a mitral isthmus and/or septal line, and a cavotricuspid isthmus line. ATa was terminated in 41 patients (35%). There were three cases of tamponade (3/170 procedures, 1.8%). Ninety-two patients (69.2%) were in sinus rhythm after a median (interquartile range) of 36 (21-53) months since the index cryoballoon PVI. Diagnosis-to-ablation time and LA area were predictors of recurrence in multivariable analysis. CONCLUSION:The creation of linear lesions is a safe and effective treatment strategy for the recurrence of persistent ATa after cryoballoon PVI. Longer diagnosis-to-ablation time and larger LA area were predictive of ATa recurrence.

AIMS:In arrhythmogenic cardiomyopathy (ACM), sustained ventricular tachycardia (VT) typically displays a left bundle branch block (LBBB) morphology while a right bundle branch block (RBBB) morphology is rare. The present study assesses the VT morphology in ACM patients with sustained VT and their clinical and genetic characteristics. METHODS AND RESULTS:Twenty-six centres from 11 European countries provided information on 954 ACM patients who had ≥1 episode of sustained VT spontaneously documented during patients' clinical course. Arrhythmogenic cardiomyopathy was defined according to the 2010 Task Force Criteria, and VT morphology according to the QRS pattern in V1. Overall, 882 (92.5%) patients displayed LBBB-VT alone and 72 (7.5%) RBBB-VT [alone in 42 (4.4%) or in combination with LBBB-VT in 30 (3.1%)]. Male sex prevalence was 79.3%, 88.1%, and 56.7% in the LBBB-VT, RBBB-VT, and LBBB + RBBB-VT groups, respectively (P = 0.007). First RBBB-VT occurred 5 years after the first LBBB-VT (46.5 ± 14.4 vs 41.1 ± 15.8 years, P = 0.011). An implanted cardioverter-defibrillator was more frequently implanted in the RBBB-VT (92.9%) and the LBBB + RBBB-VT groups (90%) than in the LBBB-VT group (68.1%) (P < 0.001). Mutations in PKP2 predominated in the LBBB-VT (65.2%) and the LBBB + RBBB-VT (41.7%) groups while DSP mutations predominated in the RBBB-VT group (45.5%). By multivariable analysis, female sex was associated with LBBB + RBBB-VT (P = 0.011) while DSP mutations were associated with RBBB-VT (P < 0.001). After a median follow-up of 103 (51-185) months, death occurred in 106 (11.1%) patients with no intergroup difference (P = 0.176). CONCLUSION:RBBB-VT accounts for a significant proportion of sustained VTs in ACM. Sex and type of pathogenic mutations were associated with VT type, female sex with LBBB + RBBB-VT, and DSP mutation with RBBB-VT.

Atrial fibrillation (AF) is the most frequent heart rhythm disorder, affecting 33.5 million people worldwide in 2010.The incidence of AF increased to a greater extent in developed than in developing countries between 1990 and 2010.AF increases the risks of stroke and heart failure and the rates of hospitalization and mortality.The estimated age-adjusted incidence per 100,000 inhabitants is higher for men than for women: 77.5 (95% CI, 65.2-95.4)versus 59.5 (95% CI, 49.9-74.9) in 2010 [1].The first-line treatment of symptomatic paroxysmal AF is based on antiarrhythmic drugs.In accordance with the European Society of Cardiology (ESC) recommendations, percutaneous catheter ablation is reserved for patients with symptomatic episodes despite treatment with antiarrhythmic drugs (class I indication).Several randomized studies have demonstrated its efficacy in this context [2].Catheter ablation of symptomatic paroxysmal AF in first line is only a class IIa indication [2].This recommendation resulted from the publication of the RAAFT 1 and 2 and MANTRA PAF studies, which found a high rate of recurrences in the two groups and a worrying number of complications in the ablation group.In addition, the results of the MANTRA PAF study, despite indicating a trend towards lower rates of recurrence with ablation, did not reach statistical significance.It is only by compiling the data from these 3 studies, corresponding to a total of 491 patients, that a meta-analysis showed that catheter ablation appeared to be superior [3].Three new randomized trials comparing firstline ablation, this time by cryoballoon, with antiarrhythmic drugs, were published in 2021.

BackgroundThe literature data on the outcomes of radiofrequency catheter ablation for atrial fibrillation (AF) in women are contradictory.AimTo determine and compare the outcomes and complications of cryoballoon pulmonary vein isolation (cryo-PVI) in men vs. women, and to identify predictors of atrial tachyarrhythmia (ATa) recurrence.MethodsWe included all consecutive patients having undergone cryo-PVI for the treatment of symptomatic AF in our center since 2012. Peri-operative complications were documented. All patients were prospectively monitored for the recurrence of ATa, and predictors were assessed.ResultsA total of 733 patients were included (550 men (75%) and 183 (25%) women). Paroxysmal AF was recorded in 112 (61%) female patients and 252 male patients (46%; p < 0.001). Female patients were older (p < 0.001) and had a greater symptom burden (p = 0.04). Female patients were more likely to experience complications (p = 0.02). After cryo-PVI for paroxysmal AF, 66% of the female patients and 79% of the male patients were free of ATa at 24 months (p = 0.001). Female sex was the only independent predictive factor for ATa recurrence (hazard ratio [95% confidence interval] = 1.87 [1.28; 2.73]; p = 0.001). After cryo-PVI for non-paroxysmal AF, 37% of the male patients and 39% of the female patients were free of ATa at 36 months (p = 0.73). Female patients were less likely than male patients to undergo repeat ablation after an index cryo-PVI for non-paroxysmal AF (p = 0.019).ConclusionA single cryo-PVI procedure for paroxysmal AF was significantly less successful in female patients than in male patients. Overall, the complication rate was higher in women than in men.

We report a detailed case of type 2 TS due to a p.(Gly402Ser) mutation in exon 8 of the CACNA1C gene. The patient shows a marked prolongation of repolarization with a mean QTc of 540 ms. He shows no structural heart disease, syndactyly, or cranio-facial abnormalities. However, he shows developmental delays, without autism, and dental abnormalities. The cardiac phenotype is very severe, with a resuscitated cardiac arrest at 2.5 years of age, followed by 26 appropriate shocks during nine years of follow-up. Adding mexiletine to nadolol resulted in a reduction of the QTc and a slight decrease in the number of appropriate shocks.

A 79-year-old woman was referred to our centre for left atrial appendage (LAA) occlusion. She had permanent atrial fibrillation and experienced bleeding while being treated with rivaroxaban. Her Congestive Heart Failure, Hypertension, Age (≥75 years), Diabetes, Stroke/Transient Ischemic Attack, Vascular Disease, Age (65-74 years), Sex (Female) (CHA2DS2-VASc) score was 9 (congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease, female). Transseptal access was achieved, guided by transesophageal echocardiography. We then introduced the occluder delivery system into the left atrium, without difficulty. The system was perfused with saline with an autopump. Contrast was injected into the LAA (Fig. 1). After delivery of the device, contrast was injected again. Just after, we clearly visualized an air bubble trapped in the LAA (Fig. 2). We provide a video showing the bubble moving into the LAA (Video 1 view video online). We immediately examined the delivery system and noted that the valve was unclipped from the delivery sheath. We had to push strongly to correctly reclip it. The transesophageal echocardiography did not show any flow from the LAA after device placement.Figure 2Air bubble trapped in the left atrial appendage. (Red arrows) point the bubble.View Large Image Figure ViewerDownload Hi-res image Download (PPT) We finished the procedure and tried to once again unclip the valve, which proved to be impossible. We conclude that the system had a manufacturing defect. Our patient did not experience an ischemic event in relation to this accident. Forty-eight hours later, we performed an x-ray and noted the spontaneous disappearance of the bubble. This case, which could have ended badly, is a reminder that the material integrity of devices must be verified before starting a procedure.Novel Teaching Points•An air bubble trapped in the left atrial appendage can disappear spontaneously.•Careful examination of the material integrity of the device is needed before starting any percutaneous procedure. •An air bubble trapped in the left atrial appendage can disappear spontaneously.•Careful examination of the material integrity of the device is needed before starting any percutaneous procedure. The authors report no funding sources.

Aims Treatment guidelines for patients with atrial fibrillation (AF) suggest that patients should be managed with an anti-arrhythmic drug (AAD) before undergoing catheter ablation (CA). This study evaluated whether pulmonary vein isolation employing cryoballoon CA is superior to AAD therapy for the prevention of atrial arrhythmia (AA) recurrence in rhythm control naive patients with paroxysmal AF (PAF). Methods and results A total of 218 treatment naive patients with symptomatic PAF were randomized (1:1) to cryoballoon CA (Arctic Front Advance, Medtronic) or AAD (Class I or III) and followed for 12 months. The primary endpoint was >= 1 episode of recurrent AA (AF, atrial flutter, or atrial tachycardia) >30 s after a prespecified 90-day blanking period. Secondary endpoints included the rate of serious adverse events (SAEs) and recurrence of symptomatic palpitations (evaluated via patient diaries). Freedom from AA was achieved in 82.2% of subjects in the cryoballoon arm and 67.6% of subjects in the AAD arm (HR= 0.48, P= 0.01). There were no group differences in the time-to-first (HR= 0.76, P = 0.28) or overall incidence [incidence rate ratio (IRR)=0.79, P = 0.28] of SAEs. The incidence rate of symptomatic palpitations was lower in the cryoballoon (7.61 days/year) compared with the AAD arm (18.96 days/year; IRR= 0.40, P < 0.001). Conclusions Cryoballoon CA was superior to AAD therapy, significantly reducing AA recurrence in treatment naive patients with PAF. Additionally, cryoballoon CA was associated with Lower symptom recurrence and a similar rate of SAEs compared with AAD therapy. [GRAPHICS] .

The French left atrial appendage (LAA) closure registry (FLAAC) aimed to assess the safety and efficacy of LAA closure in daily practice.

Background Percutaneous left atrial appendage (LAA) closure is an alternative to oral anticoagulation (OAC) for atrial fibrillation (AF) patients with high thromboembolism risk, particularly with contraindications to OAC. The LAA itself could possess proarrhythmogenic properties. As patients undergoing LAA closure could be candidates for cardioversion or ablation, we aimed to evaluate AF disease progression following LAA closure and the outcome of patients undergoing a rhythm control strategy after the procedure. Methods The prospective multicenter French Nationwide Observational LAA Closure Registry (FLAAC) comprises 33 French interventional cardiology departments. Patients were included if they fulfilled the following criteria: history of non-valvular AF, successful LAA closure and long-term ECG follow-up. Results A total of 331 patients with successful LAA closure were enrolled in the study. Patients mean age was 75.4 ± 0.5 years. The study population was characterized by a high thromboembolic risk (CHA 2 DS 2 -VASc score: 4.5 ± 0.1) and frequent comorbidities. The median follow-up was 11.9 months. One hundred and nineteen (36.0%) patients were in sinus rhythm (SR) at baseline. Among SR patients, documented AF was observed in 16 (13.4%) patients whereas 15 (7.1%) patients in AF at baseline restored SR, at the end of follow up. Finally, only 13 patients (4%) underwent procedures to restore SR without complications during the follow-up. Conclusions The vast majority of patients undergoing LAA closure have the same AF status at baseline and one year after the index procedure. During the follow-up, a very small proportion (4%) of our population underwent procedures to restore SR without complications whatever the post-procedural antithrombotic strategy was.

Abstract Aims  We aimed to provide contemporary real-world data on wearable cardioverter-defibrillator (WCD) use, not only in terms of effectiveness and safety but also compliance and acceptability. Methods and results  Across 88 French centres, the WEARIT-France study enrolled retrospectively patients who used the WCD between May 2014 and December 2016, and prospectively all patients equipped for WCD therapy between January 2017 and March 2018. All patients received systematic education session through a standardized programme across France at the time of initiation of WCD therapy and were systematically enrolled in the LifeVest Network remote services. Overall, 1157 patients were included (mean age 60 ± 12 years, 16% women; 46% prospectively): 82.1% with ischaemic cardiomyopathy, 10.3% after implantable cardioverter-defibrillator explant, and 7.6% before heart transplantation. Median WCD usage period was 62 (37–97) days. Median daily wear time of WCD was 23.4 (22.2–23.8) h. In multivariate analysis, younger age was associated with lower compliance [adjusted odds ratio (OR) 0.97, 95% confidence interval (CI) 0.95–0.99, P < 0.01]. A total of 18 participants (1.6%) received at least one appropriate shock, giving an incidence of appropriate therapy of 7.2 per 100 patient-years. Patient-response button allowed the shock to be aborted in 35.7% of well-tolerated sustained ventricular arrhythmias and in 95.4% of inappropriate ventricular arrhythmia detection, finally resulting in an inappropriate therapy in eight patients (0.7%). Conclusion Our real-life findings reinforce previous studies on the efficacy and safety of the WCD in the setting of transient high-risk group in selected patients. Moreover, they emphasize the fact that when prescribed appropriately, in concert with adequate patient education and dedicated follow-up using specific remote monitoring system, compliance with WCD is high and the device well-tolerated by the patient.

Background Cryoballoon ablation (CBA) as a first-line rhythm control strategy is superior to antiarrhythmic drugs (AADs) for preventing atrial fibrillation (AF) recurrence; the impact of first-line CBA on quality of life (QoL) and symptoms has not been well characterized. Methods Patients aged 18 to 75 with symptomatic paroxysmal AF naive to rhythm control therapy were randomized (1:1) to CBA (Arctic Front Advance, Medtronic) or AAD (Class I or III). Symptoms and QoL were assessed at baseline, 1, 3, 6, 9, and 12 months using the EHRA classification and Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) and SF-36v2 questionnaires. Symptomatic palpitations were evaluated via patient diary. Results Overall, 107 patients were randomized to CBA and 111 to AAD; crossovers occurred in 9%. Larger improvements in the AFEQT summary, subscale and treatment satisfaction scores were observed at 12 months with CBA vs AAD (all P < 0.05). At 12 months, the mean adjusted difference in the AFEQT summary score was 9.9 points higher in the CBA group (95% CI: 5.5 -14.2, P < 0.001). Clinically important improvements in the SF-36 physical and mental component scores were observed at 12 months in both groups, with no significant between group differences at this timepoint. In the CBA vs AAD group, larger improvements in EHRA class were observed at 6, 9 and 12 months ( P < 0.05) and the incidence rate of symptomatic palpitations was lower (4.6 vs 15.2 days/year post-blanking; IRR: 0.30, P < 0.001). Conclusions In patients with symptomatic AF, first-line CBA was superior to AAD for improving AF-specific QoL and symptoms. Trial registration ClinicalTrials.gov number: NCT01803438.

Late initiation of antiretrovirals in pregnancy is associated with increased risk of perinatal transmission and higher infant mortality. We report the final 72-week postpartum results for efficacy and safety of dolutegravir-based compared with efavirenz-based regimens in mothers and infants.DolPHIN-2 was a randomised, open-label trial. Pregnant women in South Africa and Uganda aged at least 18 years, with untreated but confirmed HIV infection and an estimated gestation of at least 28 weeks, initiating antiretroviral therapy in third trimester were eligible for inclusion. Eligible women were randomly assigned (1:1) to receive either dolutegravir-based (50 mg dolutegravir, 300 mg tenofovir disoproxil fumarate, and either 200 mg emtricitabine in South Africa or 300 mg lamivudine in Uganda) or efavirenz-based (fixed dose combination 600 mg tenofovir disoproxil fumarate plus either emtricitabine in South Africa or lamivudine in Uganda) therapy. The primary efficacy outcome was the time to a viral load of less than 50 copies per mL measured at 6, 12, 24, 48, and 72 weeks postpartum with a Cox model adjusting for viral load and CD4 cell count. Safety endpoints were summarised by the number of women and infants with events. This trial is registered with ClinicalTrials.gov, NCT03249181.Between Jan 23 and Aug 15, 2018, 280 women were screened for inclusion, of whom 268 (96%) women were randomly assigned: 133 (50%) to the efavirenz group and 135 (50%) to the dolutegravir group. 250 (93%; 125 [50%] in the efavirenz group and 125 [50%] in the dolutegravir group) women were included in the intention-to-treat analysis of efficacy. Median time to viral load of less than 50 copies per mL was 4·1 weeks (IQR 4·0–5·1) in the dolutegravir group compared with 12·1 weeks (10·7–13·3) in the efavirenz group (adjusted hazard ratio [HR] 1·93 [95% CI 1·5–2·5]). At 72 weeks postpartum, 116 (93%) mothers in the dolutegravir group and 114 (91%) in the efavirenz group had a viral load of less than 50 copies per mL. Of 57 (21%) mothers with a severe adverse event, three (2%) in the dolutegravir group and five (4%) in the efavirenz group were related to the drug (dolutegravir drug-related events were one woman each with suicidal ideation, suicide attempt, herpes zoster meningitis; efavirenz drug-related events were one woman each with suicide attempt and liver cirrhosis, and three people with drug-induced liver injury). Of 136 (56%) infants in whom severe adverse events were recorded, none were related to the study drugs. In addition to the three infant HIV infections detected at birth in the dolutegravir group that have been previously reported, an additional transmission in the efavirenz group occurred during breastfeeding despite optimal maternal viral suppression and serial negative infant tests in the first year of life.Dolutegravir was safe and well tolerated, supporting updated WHO treatment recommendations in pregnant and breastfeeding women. Infant HIV transmissions can occur during breastfeeding despite persistently undetectable maternal viral load highlighting the need for continued infant testing.Unitaid.

Cryoballoon pulmonary vein isolation (PVI) for persistent atrial fibrillation (AF) ablation is an increasingly used strategy. We aimed to determine the results and predictors of arrhythmia recurrence after a single procedure of cryoballoon PVI for patients with persistent and long-standing persistent AF. We included all consecutive patients who underwent cryoballoon PVI for the treatment of persistent symptomatic drug-refractory AF since 2012. All patients were prospectively followed to detect the recurrence of atrial tachyarrhythmia (ATa). Predictors of recurrence were assessed. Cryoballoon PVI was performed on 399 patients with persistent AF, among whom 52 (13%) had long-standing persistent AF. Patients with long-standing persistent AF had a significantly larger left atrium than those with persistent AF. A 28-mm cryoballoon was used for 322 patients (93%). In total, 359 patients (90%) completed the 12-month follow-up visit and the median follow-up was 24 months (interquartile range 43 to 13). The 2-year probability of freedom from ATa recurrence was 51% for persistent AF and 27% for long-standing persistent AF. Long-standing persistent AF and left atrial area/volume were independent predictors of ATa recurrence. Ten patients (2.5%) experienced phrenic nerve palsy, 1 tamponade (0.25%), 2 stroke (0.5%), 2 pericardial effusions (0.5%), and 5 vascular complications (1.25%). In conclusion, 2-year ATa-free survival rates were 51 and 27% for persistent and long-standing persistent AF patients, respectively. Complications were rare. Long-standing persistent AF and left-atrial area/volume were predictors of recurrence.

Atrial fibrillation (AF) catheter ablation is more and more performed without interruption of direct oral anticoagulants (DOAC), with a risk of puncture site complications. To evaluate safety and feasibility of figure-of eight-suture to achieve hemostasis of puncture site in AF catheter ablation without interruption of DOAC. All patients receiving DOAC who underwent AF catheter ablation from November 2017 to December 2018 were prospectively enrolled. Unfractionated heparin (UH) was administrated during the procedure to obtain a target ACT > 300s. At the end of the procedure, a last ACT was assayed and a figure-of-eight suture was performed to remove the sheaths, without further manual compression. Puncture site complications were recorded during the hospitalization and at the 3 months control consultation. One hundred and thirty-eight patients underwent AF catheter ablation without DOAC interruption with a median follow-up of 119 days (99–149). Median last ACT before sheath removal was 300s (259–337). Figure-of-eight suture was able to be performed in all patients. No protamine reversal was necessary to obtain puncture site hemostasis. Puncture site complications occured in 8 patients (hematoma: 4; 2.9% − pseudoaneurysm: 1;0.7% − arteriovenous fistula (AVF): 2;1.4%). All complications were detected during hospitalization except for one patient for which pseudoaneurysm was diagnosed and treated ambulatory. Only 2 (1.4%) patients needed to be treated surgically for AVF. No death was reported. Figure-of-eight suture is safe and feasible to achieve puncture site hemostasis, without manual compression or protamine reversal, in AF catheter ablation without DOAC interruption.

BACKGROUND:Long-term outcomes in terms of thromboembolic events (TEs) are poorly described after cryoballoon pulmonary vein isolation (cryo-PVI) for atrial fibrillation (AF). We evaluated the long-term incidence and predictive factors of TE after cryo-PVI. METHODS:All consecutive patients who underwent cryo-PVI for paroxysmal or persistent AF between November 2012 and October 2017 were included. They were prospectively followed for at least 12 months in the ablation center and then by their cardiologist. Data on all ischemic events (stroke, transient ischemic attack (TIA), systemic embolism) were collected. RESULTS:In total, 450 patients (78% men, median age 61 years) were included. The mean CHA2DS2-VASc score was 1.6 ± 1.3 and 26 patients (6%) had a history of stroke/TIA before the procedure. OAT was discontinued for 75 patients (17%) after the procedure, among whom 50 (67%) had no indication for long-term anticoagulation. Six patients experienced an ischemic event, all considered as a TE: three strokes, two TIAs, and one acute lower-limb ischemia. The mean follow up was 30 months. Thus, the incidence of TE was 0.53%/year. Three of the six patients who experienced a TE had no recurrence of atrial arrhythmia documented before, at the time, or after the event. All patients who experienced a TE had a class I or class IIa indication for long-term anticoagulation. After multivariate analysis, the CHA2DS2-VASc Score (p = .0005) was a predictor of TEs. CONCLUSION:The long-term incidence of TEs after cryo-PVI was 0.53%/year. The CHA2DS2-VASc Score was the only independent predictor of TEs.