Virtual Reality for Sedation During Atrial Fibrillation Ablation in Clinical Practice: Observational Study.

BACKGROUND: Connected devices are dramatically changing many aspects in health care. One such device, the virtual reality (VR) headset, has recently been shown to improve analgesia in a small sample of patients undergoing transcatheter aortic valve implantation. OBJECTIVE: We aimed to investigate the feasibility and effectiveness of VR in patients undergoing atrial fibrillation (AF) ablation under conscious sedation. METHODS: All patients who underwent an AF ablation with VR from March to May 2020 were included. Patients were compared to a consecutive cohort of patients who underwent AF ablation in the 3 months prior to the study. Primary efficacy was assessed by using a visual analog scale, summarizing the overall pain experienced during the ablation. RESULTS: The AF cryoablation procedure with VR was performed for 48 patients (mean age 63.0, SD 10.9 years; n=16, 33.3% females). No patient refused to use the device, although 14.6% (n=7) terminated the VR session prematurely. Preparation of the VR headset took on average 78 (SD 13) seconds. Compared to the control group, the mean perceived pain, assessed with the visual analog scale, was lower in the VR group (3.5 [SD 1.5] vs 4.3 [SD 1.6]; P=.004), and comfort was higher in the VR group (7.5 [SD 1.6] vs 6.8 [SD 1.7]; P=.03). On the other hand, morphine consumption was not different between the groups. Lastly, complications, as well as procedure and fluoroscopy duration, were not different between the two groups. CONCLUSIONS: We found that VR was associated with a reduction in the perception of pain in patients undergoing AF ablation under conscious sedation. Our findings demonstrate that VR can be easily incorporated into the standard ablation workflow.

Hypnosis Versus Placebo During Atrial Flutter Ablation: The PAINLESS Study: A Randomized Controlled Trial.

OBJECTIVES: The aim of this study was to assess the superiority of hypnosis versus placebo on pain perception and morphine consumption during typical atrial flutter (AFL) ablation. BACKGROUND: AFL ablation commonly requires intravenous opioid for analgesia, which can be associated with adverse outcomes. Hypnosis is an alternative technique with rising interest, but robust data in electrophysiological procedures are lacking. METHODS: This single center, randomized controlled trial compared hypnosis and placebo during AFl ablation. In addition to the randomized intervention, all patients were treated according to the institution's standard of care analgesia protocol (administration of 1 mg of intravenous morphine in case of self-reported pain ≥5 on an 11-point numeric rating scale or on demand). The primary endpoint was perceived pain quantified by patients using a visual analog scale. RESULTS: Between October 2017 and September 2019, 113 patients (mean age 70 ± 12 years, 21% women) were randomized to hypnosis (n = 56) or placebo (n = 57). Mean pain score was 4.0 ± 2.2 in the hypnosis group versus 5.5 ± 1.8 in the placebo group (p < 0.001). Pain perception, assessed every 5 min during the whole procedure, was consistently lower in the hypnosis group. Patients' sedation scores were also better in the hypnosis group than in the placebo group (8.3 ± 2.2 vs. 5.4 ± 2.5; p < 0.001). Finally, morphine requirements were significantly lower in the hypnosis group (1.3 ± 1.3 mg) compared with the placebo group (3.6 ± 1.8 mg; p < 0.001). CONCLUSIONS: In this first randomized trial, hypnosis during AFL ablation was superior to placebo for alleviating pain and reducing morphine consumption.

Prognostic value of Charlson Comorbidity Index in the elderly with a cardioverter defibrillator implantation.

BACKGROUND: Elderly patients are often underrepresented in implantable cardioverter defibrillator (ICD) trials, and ICD implantation in patients ≥75 years consequently remains controversial. We aimed to evaluate mortality, appropriate ICD therapy rates and survival gain in an elderly population after risk stratification according to the Charlson Comorbidity Index (CCI). METHODS: This monocentric retrospective study included elderly ICD patients ≥75 years. They were subdivided according to their CCI score into 3 categories (0-1, 2-3 or ≥4 points). Elderly patients were matched 1:2 with younger control ICD patients on gender, type of prevention (primary or secondary) and type of device (associated cardiac resynchronization therapy or not). RESULTS: Between January 2009 and July 2017, 121 elderly patients (mean age 78 ± 3; 83% male) matched with 242 controls (mean age 66 ± 5) were included. At 5 year follow-up after ICD implantation, overall survival was 78%, 57%, and 29% (P = 0.002) in the elderly with a CCI score of 0-1, 2-3 and ≥4 respectively, and 72% in controls. There was no significant difference regarding ICD appropriate therapy between the 3 subgroups despite a trend towards lower rates of therapy in CCI ≥ 4 points patients (34.2%, 39.7% and 22.8% respectively; P = 0.45). Median potential survival gain after an appropriate therapy was >5, 4.7 and 1.4 years, with a CCI score of 0-1, 2-3 and ≥4 respectively (P = 0.01). CONCLUSION: Elderly patients with CCI score ≥ 4 had the lowest survival after ICD implantation and little survival gain in case of appropriate defibrillator therapy. More than age alone, the burden of comorbidities assessed by the CCI could be helpful to better select elderly patients for ICD implantation.

[Screening and diagnosis of atrial fibrillation]. / Dépistage et diagnostic de la fibrillation atriale.

Screening and diagnosis of atrial fibrillation. Screening for atrial fibrillation (AF) is crucial as this arrhythmia is asymptomatic in a third of patients and 5% of patients present a stroke as the first manifestation of their AF. The European Society of Cardiology recommends opportunistic screening of AF in patients over 65 years of age and systematically in patients over 75 years of age. The simplest way is pulse taking, but the number of connected devices for AF screening allows to multiply the frequency of screening and thus increase sensitivity, with another advantage of a digitalized transmission of the tracing. However many questions remain. No scientific evidence has demonstrated a benefit for AF screening. We do not know what duration and frequency of screening is relevant. The burden of AF which increases thromboembolic risk is not known. What population should be screened and how to consider subclinical AF? We will obtain answers to our questions in the coming years thanks to the results of the various studies in progress.

Dépistage et diagnostic de la fibrillation atriale. Le dépistage de la fibrillation atriale (FA) est primordial, car cette arythmie est asymptomatique chez 15 à 30 % des patients, et 1 patient sur 20 est victime d'un accident vasculaire cérébral comme première manifestation de sa fibrillation. La Société européenne de cardiologie recommande le dépistage de la FA de manière opportuniste chez les plus de 65 ans et de manière systématique chez les plus de 75 ans. Le moyen le plus simple est la prise du pouls, mais les objets connectés permettent dorénavant de multiplier la fréquence de dépistage, et donc d'augmenter la sensibilité, avec aussi l'avantage d'une transmission numérisée du tracé pour la plupart. Enfin, ils sont moins contraignants que les appareils les plus anciens. Toutefois, de nombreuses questions demeurent. Il n'y a pas encore de preuve scientifique ayant démontré un bénéfice du dépistage de la FA. Nous ne savons pas quelle durée et quelle fréquence de dépistage sont pertinentes. La durée de fibrillation à partir de laquelle il existe une augmentation du risque thromboembolique n'est pas connue. Quelle population faut-il dépister et comment faut-il considérer la fibrillation infraclinique ? Nous obtiendrons des réponses à nos interrogations dans les prochaines années grâce aux résultats des différentes études en cours.

Baroreflex sensitivity assessed with the sequence method is associated with ventricular arrhythmias in patients implanted with a defibrillator for the primary prevention of sudden cardiac death.

BACKGROUND: Left ventricular ejection fraction lacks accuracy in predicting sudden cardiac death, resulting in unnecessary implantation of cardioverter defibrillators for the primary prevention of sudden cardiac death. Baroreflex sensitivity could help to stratify patients at risk of ventricular arrhythmia. AIM: To assess the association between cardiac baroreflex sensitivity and ventricular arrhythmias in patients implanted with an implantable cardioverter defibrillator for the primary prevention of sudden cardiac death after myocardial infarction. METHODS: This case-control single-centre study took place between 2015 and 2016. Cases (n=10) had experienced ventricular arrhythmias treated by the implantable cardioverter defibrillator in the previous 3 years; controls (n=22) had no arrhythmia during the same period. Baroreflex sensitivity was assessed using the temporal sequence method (mean slope) and cross-spectral analysis (low-frequency gain and high-frequency gain). RESULTS: The mean age was 65 years; 94% of the patients were men. 24-hour Holter electrocardiogram autonomous nervous system variables, left ventricular ejection fraction and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) concentration did not differ between cases and controls. The mean slope was lower in cases than in controls (8 vs. 15ms/mmHg [P=0.009] in the supine position; 7 vs. 12ms/mmHg [P=0.038] in the standing position). The mean slope in the supine position was still significantly different between groups after adjustment for age, left ventricular ejection fraction and NT-proBNP (P=0.03). By comparison, low-frequency gain and high-frequency gain did not differ between groups in either the supine or the standing position. CONCLUSION: Patients with ventricular arrhythmias had a lower mean slope compared with those who were free of arrhythmia. A prospective study is needed to confirm this association.

Twenty-four-hour ambulatory ECG monitoring relevancy in myotonic dystrophy type 1 follow-up: Prognostic value and heart rate variability evolution.

BACKGROUND: Patient prognosis in type 1 myotonic dystrophy (DM1) is very poor. Annual 24-hour holter ECG monitoring is recommended but its relevance is debated. Main objective was to determine whether holter ECG parameters could predict global death in DM1 patients and secondarily to assess whether they could predict cardiovascular events and sudden cardiac death, to compare DM1 patients and healthy controls, and to assess their evolution in DM1 over a 5-year period. METHODS: This retrospective study included genetically confirmed DM1. Primary endpoint was global death. Secondary endpoints were labeled "sudden cardiac death" which was a composite of sudden cardiac death, aborted sudden cardiac death, implantable cardioverter defibrillator therapy, sustained ventricular tachycardia, atrioventricular block grade 3, pause >3 s; and "cardiovascular events" which was a composite of all-cause mortality, pacemaker or cardioverter defibrillator implantation, sustained ventricular tachycardia, supraventricular tachycardia, hospitalization for acute cardiac cause and heart failure. RESULTS: Forty-seven patients (22 women, 40 ± 13 years old) were included. Three (7%) DM1 patients died, 9 (19%) experienced "sudden cardiac death" endpoint and 21 (45%) experienced "cardiovascular event" endpoint during mean follow-up of 95 ± 22 months. None of holter ECG parameters were discriminant to predict death or secondary endpoints. Compared to healthy controls, DM1 patients had higher SDNN and LF/HF ratio. Finally, heart rate variability parameters remained stable over a mean interval of 61 ± 15 months excepting pNN50 which decreased significantly. CONCLUSION: Results suggest that annually-repeated holter ECG in DM1 is not useful for stratifying risk of sudden death and cardiovascular outcomes.

Contractibility sensor signal evolution predicts cardiovascular events in patients with cardiac resynchronization therapy.

BACKGROUND: While a multicentre trial has demonstrated that the SonR™ contractibility sensor is as effective as echocardiography-guided optimization at improving response to cardiac resynchronization therapy, an association between SonR™ values and clinical endpoints has not been established. AIMS: The primary objective was to assess the predictive value of SonR™ signal evolution regarding cardiovascular events in patients implanted with a cardiac resynchronization therapy device. The secondary objective was to evaluate whether SonR™ signal evolution was associated with cardiovascular death. METHODS: All patients with a SonR™ system implanted between 2012 and 2016 were included in this retrospective study. SonR™ signal evolution was calculated over the first 6 months after implantation: ([month 6 value-month 1 value]/month 1 value)*100. The primary endpoint (cardiovascular events) was a composite of cardiovascular death, hospitalization for acute heart failure or ventricular arrhythmia. RESULTS: Seventy-four patients (median age 67 years; 81% men) were followed up over a median 20 (13; 29) months. Cumulative incidence function showed that SonR™ signal evolution was predictive of cardiovascular events (threshold<10.70%; P=0.023) and predictive of cardiovascular death (P=0.0018). After multivariable analysis, SonR™ signal evolution was independently associated with the onset of cardiovascular events (hazard ratio: 4.03, 95% confidence interval: 1.31-12.43; P=0.015), even after adjustment for left bundle branch block and chronic kidney disease. CONCLUSIONS: In this first study publishing data on SonR™ signals in a real-life setting, SonR™ signal evolution over the first 6 months after cardiac resynchronization implantation was an independent predictor of cardiovascular events at follow-up. This variable could be useful to identify patients at higher risk of further adverse events after cardiac resynchronization implantation.

Left ventricular longitudinal strain impairment predicts cardiovascular events in asymptomatic type 1 myotonic dystrophy.

BACKGROUND: Type 1 myotonic dystrophy (DM1) patients' prognosis is very poor. Up until now, only a few prognostic factors for cardiovascular events have been identified, and they are predictive of end-stage disease. The aim was to assess the prognostic value of global longitudinal strain (GLS) for cardiovascular events in asymptomatic DM1 patients. METHODS: DM1 patients were included between 2011 and 2015 and followed up until January 2016. Patients underwent a transthoracic echocardiography at inclusion. The primary endpoint was a composite of all-cause mortality, type 2 Mobitz 2 and type 3 atrioventricular block, symptomatic sino-atrial block, HV interval≥70ms at invasive electrophysiology exploration, left ventricular ejection fraction (LVEF) ≤45% and newly developed atrial fibrillation. RESULTS: Forty-six patients (25 males, mean age 40years old) were included. The primary outcome was reached in 14 patients with a mean follow-up of 38months. GLS of patients who reached the primary endpoint was significantly impaired as compared to those who did not (-15.1 [-16.7; -12.7] vs. -18.2 [-19.2; -16.7] respectively; P=0.001). According to ROC curve analysis, probability of primary outcome occurrence was significantly greater in patients with GLS values≥-17.2% (P=0.001). On multivariate analysis, PR electrocardiogram interval and GLS remained significantly and independently associated with the primary endpoint [hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01-1.04, P=0.006 for PR interval; HR 1.4, 95% CI 1.1-1.7, P=0.002 for GLS] while LVEF alone was not. CONCLUSION: Left ventricular GLS is a powerful marker to predict cardiovascular events in asymptomatic DM1 patients, independently of LVEF.

Apical left ventricular myocardial dysfunction is an early feature of cardiac involvement in myotonic dystrophy type 1.

INTRODUCTION: Left ventricular (LV) dysfunction is a major prognostic determinant in myotonic dystrophy type 1 (DM1). Therefore, markers of early-stage LV impairment may be useful. The aim of this study was to evaluate 2D echocardiographic LV strain in a cohort of DM1 patients with preserved left ventricular ejection fraction (LVEF) and to compare the results with matched controls. METHODS: This prospective single-center study included 33 consecutive DM1 patients between February 2014 and February 2015. Mean age was 38.2±12.9 years, and 17 (52%) were males. Exclusion criteria were LVEF <55%, QRS >120 milliseconds, history of atrial fibrillation, and presence of a pacemaker with ventricular pacing. DM1 patients were matched to healthy controls according to sex and age. RESULTS: DM1 patients showed significant impairment of global longitudinal strain (GLS) as compared to controls (-18.0±1.9 vs -19.1±2.4; P=.03), characterized by a marked alteration at the apex (-20.0±3.3 vs -22.7±3.1; P<.001). DM1 patients had also global radial strain impairment (20.0±9.8 vs 27.5±14.9; P=.024) compared to controls while global circumferential strain was not statistically different between groups (P=.94). Intra- and inter-observer analysis showed good reproducibility of GLS. CONCLUSION: Despite preserved LVEF, DM1 patients exhibited significantly altered LV GLS, particularly at the apex, as compared with controls. The detection of impaired myocardial deformation at early stages of the disease might help to screen high-risk patients who need closer follow-up.

When is a child with status epilepticus likely to have Dravet syndrome?

PURPOSE: To identify clinical risk factors for Dravet syndrome (DS) in a population of children with status epilepticus (SE). MATERIAL AND METHODS: Children aged between 1 month and 16 years with at least one episode of SE were referred from 6 pediatric neurology centers in Switzerland. SE was defined as a clinical seizure lasting for more than 30min without recovery of normal consciousness. The diagnosis of DS was considered likely in previously healthy patients with seizures of multiple types starting before 1 year and developmental delay on follow-up. The presence of a SCN1A mutation was considered confirmatory for the diagnosis. Data such as gender, age at SE, SE clinical presentation and recurrence, additional seizure types and epilepsy diagnosis were collected. SCN1A analyses were performed in all patients, initially with High Resolution Melting Curve Analysis (HRMCA) and then by direct sequencing on selected samples with an abnormal HRMCA. Clinical and genetic findings were compared between children with DS and those with another diagnosis, and statistical methods were applied for significance analysis. RESULTS: 71 children with SE were included. Ten children had DS, and 61 had another diagnosis. SCN1A mutations were found in 12 of the 71 patients (16.9%; ten with DS, and two with seizures in a Generalized Epilepsy with Febrile Seizures+(GEFS+) context). The median age at first SE was 8 months in patients with DS, and 41 months in those with another epilepsy syndrome (p<0.001). Nine of the 10 DS patients had their initial SE before 18 months. Among the 26 patients aged 18 months or less at initial SE, the risk of DS was significantly increased for patients with two or more episodes (56.3%), as compared with those who had only one episode (0.0%) (p=0.005). CONCLUSION: In a population of children with SE, patients most likely to have DS are those who present their initial SE episode before 18 months, and who present with recurrent SE episodes.

Replication of association between a SCN1A splice variant and febrile seizures.

In the present study, we assessed a SCN1A single nucleotide polymorphism (SNP) (rs3812718, IVS5N+5 G>A), first analyzed by Schlachter et al. We genotyped 164 patients with febrile seizures (FS) [of those 62 adults with focal epilepsy (FEFS(+)) and 102 children with pure FS (Pure FS)] and 199 matched controls. Moreover, we also tested a third subgroup of 113 patients with focal epilepsy syndromes without a history of FS (FEFS(-)); they all were Caucasian. Our results, as in the initial study of Schlachter et al., showed an increase in the A-allele and AA-genotype frequencies in patients with FS compared to the controls, but these current differences did not reach statistical significance. Subsequently, we pooled our data with previously published Caucasian groups. No statistically significant difference was found for the FEFS(-), but analyses for FEFS(+) and Pure FS are significantly different compared to controls (p = 8.08 e(-6) and p = 3.56 e(-4), respectively). Furthermore, pooled patients with FS (FS + FEFS(+)) tested against those without FS (Controls + FEFS(-)) showed an even greater statistical significance (p = 4.82 e(-8)). These results reinforced rs3812718 involvement in FS vulnerability.

A case of SUDEP in a patient with Dravet syndrome with SCN1A mutation.

A boy with a clinical history of pharmacologically resistant Dravet syndrome died suddenly after falling asleep. The autopsy concluded that the cause of death was sudden unexpected death in epilepsy (SUDEP). Postmortem molecular analysis of the SCN1A gene by multiplex ligation-dependent probe amplification (MLPA), high-resolution melting curve analysis (HRMCA), and sequencing revealed a frameshift duplication of adenosine at position 504. The incidence of this mutation is discussed as a potential cause of SUDEP.

Genetic and epigenetic analysis of SSAT gene dysregulation in suicidal behavior.

It has recently been proposed that the SSAT gene plays a role in the predisposition to suicidal behavior. SSAT expression was found to be down-regulated in the brain of suicide completers. In addition, a single nucleotide polymorphism (SNP) rs6526342 was associated both with variation in SSAT expression and with suicidal behavior. In this study, we aimed to characterize the relationship between SSAT dysregulation and suicide behavior. To this end, we measured SSAT expression levels in the ventral prefrontal cortex (VPFC) of suicide completers (n = 20) and controls (n = 20) and found them to be significantly down-regulated in suicide victims (P = 0.007). To identify the basis of the regulation of SSAT expression, we performed an association analysis of 309 SNPs with SSAT transcript levels in 53 lymphoblastoid cell lines from the CEPH collection. We then examined the methylation status of the SSAT promoter region in males and females suicide completers and control subjects whose SSAT brain expression had been measured. We found no evidence to support a role for SNPs in controlling the level of SSAT expression. SSAT promoter methylation levels were not different between suicide completers and controls and did not correlate with SSAT expression levels. In addition, we found no indication of a genetic association between suicidal behavior and SNPs located within the SSAT gene. Our study provides new results which show that dysregulation of SSAT expression does play a role in suicide behavior. However, our data do not support any association between rs6526342 and variation in SSAT expression or suicidal behavior.

Chemokine analogues show suitable stability for development as microbicides.

New prevention strategies are urgently needed to slow the spread of the HIV/AIDS pandemic, and in the absence of an effective vaccine, there is hope that "microbicides"-HIV inhibitors applied to mucosal surfaces before sexual intercourse-may be able to make an impact. Because developing countries are at the center of the epidemic, affordability and stability during storage are key criteria for candidate microbicides. Furthermore, because formulation strategies that provide long-duration protection after a single dose may enhance acceptability and compliance, stability in the vaginal environment and in the presence of semen should also be considered. PSC-RANTES, a human chemokine analog, has shown promise as a candidate microbicide, but because it contains nonnatural structures that necessitate chemical synthesis steps, it is not suitable for production at a feasible cost and scale for general distribution in developing countries. We have recently developed 2 new fully recombinant chemokine analogs, 5P12-RANTES and 6P4-RANTES, which show equivalent anti-HIV activity to PSC-RANTES. In this study, we tested the stability of these molecules under conditions related to use as microbicides. Our results suggest that stability issues will not present a major obstacle to the further development of these promising molecules as microbicides.

Management of subacute and delayed right ventricular perforation with a pacing or an implantable cardioverter-defibrillator lead.

The development of small-diameter active fixation pacing and implantable cardioverter-defibrillator leads may be associated with increased risk for delayed right ventricular perforation. The management of this unforeseen complication has been poorly described. Eleven successive patients referred for right ventricular subacute or delayed perforation (no evidence of lead perforation at the time of the procedure, perforation of the right ventricle diagnosed > or =5 days after implantation) were reviewed. The perforation was related to a pacing (n = 7) or an implantable cardioverter-defibrillator (n = 4) lead. The main symptoms were major dyspnea with pericardial effusion requiring emergency pericardial drainage (n = 3), inappropriate implantable cardioverter-defibrillator shock (n = 1), syncope (n = 2), abdominal pain (n = 1), mammary hematoma (n = 1), diaphragm stimulation (n = 1), and chest pain (n = 1). One patient was strictly asymptomatic. Signs of lead dysfunction were observed in all 11 patients. The diagnosis of lead perforation was confirmed by chest x-ray, echocardiography, or computed tomography. Surgery was directly performed in 1 patient with suspicion of digestive perforation. In the remaining 10 patients, the leads were removed by simple traction under fluoroscopic guidance in the operating room, with surgical backup support. The need for close monitoring was highlighted by the occurrence in 1 patient of tamponade requiring percutaneous pericardiocentesis and urgent surgical revision. The postoperative course of these patients was unremarkable. In conclusion, subacute ventricular perforation is a rare but potentially life threatening complication of lead implantation. In most patients, the leads can safely be removed under fluoroscopic guidance, with surgical backup support and close monitoring.