A randomized trial of long-term remote monitoring of pacemaker recipients (The COMPAS trial)

International audienceAIMS: Professional practice guidelines recommend that pacemaker recipients be followed regularly. However, the majority of scheduled ambulatory visits is unproductive and imposes a heavy burden on the health-care system. METHODS AND RESULTS: The COMPAS randomized, multicentre, non-inferiority trial examined the safety of long-term remote monitoring of pacemakers. Between December 2005 and January 2008, 538 patients were randomly assigned to remote monitoring follow-up (active group) vs. standard care (control group). The primary objective was to confirm that the proportion of patients who experienced at least one major adverse event (MAE), including all-cause death and hospitalizations for device-related or cardiovascular adverse events, was not >7% higher in the active than in the control group. MAE-free survivals and quality of life were compared in both groups. The characteristics of the study groups were similar. Over a follow-up of 18.3 months, 17.3% of patients in the active and 19.1% in the control group experienced at least one MAE (P < 0.01 for non-inferiority). Hospitalizations for atrial arrhythmias (6 vs. 18) and strokes (2 vs. 8) were fewer (P < 0.05), and the number of interim ambulatory visits was 56% lower (P < 0.001) in the active than the control group. Changes in pacemaker programming or drug regimens were made in 62% of visits in the active vs. 29% in the control group (P < 0.001). Quality of life remained unchanged in both groups. CONCLUSION: Remote monitoring was a safe alternative to conventional care and significantly lowered the number of ambulatory visits during long-term follow-up of permanently paced patients. ClinicalTrials.gov identifier: NCT00989326

Impact of clinical and genetic findings on the management of young patients with Brugada syndrome.

BACKGROUND: Brugada syndrome (BrS) is an arrhythmogenic disease associated with sudden cardiac death (SCD) that seldom manifests or is recognized in childhood. OBJECTIVES: The objectives of this study were to describe the clinical presentation of pediatric BrS to identify prognostic factors for risk stratification and to propose a data-based approach management. METHODS: We studied 106 patients younger than 19 years at diagnosis of BrS enrolled from 16 European hospitals. RESULTS: At diagnosis, BrS was spontaneous (n = 36, 34%) or drug-induced (n = 70, 66%). The mean age was 11.1 ± 5.7 years, and most patients were asymptomatic (family screening, (n = 67, 63%; incidental, n = 13, 12%), while 15 (14%) experienced syncope, 6(6%) aborted SCD or symptomatic ventricular tachycardia, and 5 (5%) other symptoms. During follow-up (median 54 months), 10 (9%) patients had life-threatening arrhythmias (LTA), including 3 (3%) deaths. Six (6%) experienced syncope and 4 (4%) supraventricular tachycardia. Fever triggered 27% of LTA events. An implantable cardioverter-defibrillator was implanted in 22 (21%), with major adverse events in 41%. Of the 11 (10%) patients treated with hydroquinidine, 8 remained asymptomatic. Genetic testing was performed in 75 (71%) patients, and SCN5A rare variants were identified in 58 (55%); 15 of 32 tested probands (47%) were genotype positive. Nine of 10 patients with LTA underwent genetic testing, and all were genotype positive, whereas the 17 SCN5A-negative patients remained asymptomatic. Spontaneous Brugada type 1 electrocardiographic (ECG) pattern (P = .005) and symptoms at diagnosis (P = .001) were predictors of LTA. Time to the first LTA event was shorter in patients with both symptoms at diagnosis and spontaneous Brugada type 1 ECG pattern (P = .006). CONCLUSION: Spontaneous Brugada type 1 ECG pattern and symptoms at diagnosis are predictors of LTA events in the young affected by BrS. The management of BrS should become age-specific, and prevention of SCD may involve genetic testing and aggressive use of antipyretics and quinidine, with risk-specific consideration for the implantable cardioverter-defibrillator

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls.

PURPOSE: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate. METHODS: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants. RESULTS: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 × 10-18) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 × 10-13). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency. CONCLUSION: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing

Les édifices antiques de Rome

dessinés et mesurés tres exactement par Antoine Desgodetz ...Titel ab Frontispiz, da kein weiteres Titelblatt vorhanden. - Name des Autors: Antoine Babuty (-) Desgodets, 1653-172

Les édifices antiques de Rome

mesurés et dessinés tres-exactement sur les lieux par ... Desgodetz ..

Prognostic value of programmed ventricular stimulation in Brugada syndrome according to clinical presentation: An updated meta-analysis of worldwide published data

International audienc

Prognostic value of programmed ventricular stimulation in Brugada syndrome according to clinical presentation: An updated meta-analysis of worldwide published data

International audienc