0396: Sensitivity of sodium channel blocker in Brugada syndrome

International audienceIntroduction Brugada syndrome (BS) is characterized by a typical ECG pattern. To carrying out the diagnosis in patients without a spontaneous ECG pattern, sodium channel blocker (SCB) is used. However, the value of this test is not well known, particulary its sensibility because of a complex genetic model do not allowing the use of any mutation as a gold standard. To clarify the value of this test, we analyzed a database of 680 SCB performed in families affected by the syndrome, considering the mandatory transmitters (MT) as a true positive. Methods All patients who underwent a SCB and belonging to a family with at least 2 subjects with the syndrome were included. The MT was defined by an individual with at least one descendant in the first degree and an ascendant with a BS or unexplained sudden cardiac arrest. All the ECG data at baseline and at diagnosis was reviewed by two expert, blinded to the clinical and genetical status. Results Of the 137 selected families, 85 MT were identified. Excluding individuals who have not benefited from the SCB, sensitivity of test was calculated at 91% (42/46). According to the molecule used, the sensitivity was significantly better for ajmaline than flecainide with a sensitivity of 97% and 75% respectively (p =0.048). Among the 680 individuals who benefited a SBC, the duration of the S wave in DII, DIII and V5 and the R wave in aVR were significantly elongated at both baseline and diagnosis, in individuals with a positive SBC. Complications occurred in 1.6% of patients (11/680) including 4 required an electrical cardioversion. Risk factors present a complication was the youngest age and the occurrence of a complication with a member of his family. Conclusion This study demonstrates for the first time, the excellent sensitivity of SCB in BS, particulary with the use of ajmaline. Complications are rare and doesn’t appeared to be linked with QRS enlargement but with familial history of ventricular arythmia during the tes

NEXN gene in cardiomyopathies and sudden cardiac deaths: prevalence, phenotypic expression, and prognosis

International audienceBACKGROUND: Few clinical data are available on NEXN mutation carriers, and the gene’s involvement in cardiomyopathies or sudden death has not been fully established. Our objectives were to assess the prevalence of putative pathogenic variants in NEXN and to describe the phenotype and prognosis of patients carrying the variants. METHODS: DNA samples from consecutive patients with cardiomyopathy or sudden cardiac death/sudden infant death syndrome/idiopathic ventricular fibrillation were sequenced with a custom panel of genes. Index cases carrying at least one putative pathogenic variant in the NEXN gene were selected. RESULTS: Of the 9516 index patients sequenced, 31 were carriers of a putative pathogenic variant in NEXN only, including 2 with double variants and 29 with a single variant. Of the 29 unrelated probands with a single variant (16 males; median age at diagnosis, 32.0 [26.0–49.0] years), 21 presented with dilated cardiomyopathy (prevalence, 0.33%), and 3 presented with hypertrophic cardiomyopathy (prevalence, 0.14%). Three patients had idiopathic ventricular fibrillation, and there were 2 cases of sudden infant death syndrome (prevalence, 0.46%). For patients with dilated cardiomyopathy, the median left ventricle ejection fraction was 37.5% (26.25–50.0) at diagnosis and improved with treatment in 13 (61.9%). Over a median follow-up period of 6.0 years, we recorded 3 severe arrhythmic events and 2 severe hemodynamic events. CONCLUSIONS: Putative pathogenic NEXN variants were mainly associated with dilated cardiomyopathy; in these individuals, the prognosis appeared to be relatively good. However, severe and early onset phenotypes were also observed—especially in patients with double NEXN variants. We also detected NEXN variants in patients with hypertrophic cardiomyopathy and sudden infant death syndrome/idiopathic ventricular fibrillation, although a causal link could not be established

Discussion sur la réponse du Roi, lors de la séance du 5 octobre 1789

Goupil de Préfeln Guillaume François, Mirabeau André Boniface Louis Riqueti, vicomte de, Virieu François-Henri, comte de, Pétion de Villeneuve Jérome, Grégoire Baptiste Henri, Abbé, Maury Jean Siffrein, abbé, Monspey Louis Alexandre, marquis de, La Luzerne César Guillaume de, Camus Armand Gaston, Richier Jacques Raymond de, Coulmiers François Simmonet de, Montboissier Phillipe Claude, comte de, Mirabeau Honoré-Gabriel Riquetti, comte de, Ulry Augustin, Chasset Charles Antoine, Barrère de Vieuzac Bertrand, Bouche Charles-François, Robespierre Maximilien, Muguet de Nanthou François Felix, Duport Adrien Jean, Lameth Charles Malo, comte de, Prieur (de la Marne), Mounier Jean-Joseph, Toulongeon Hippolyte-Jean-René, marquis de. Discussion sur la réponse du Roi, lors de la séance du 5 octobre 1789. In: Archives Parlementaires de 1787 à 1860 - Première série (1787-1799) Tome IX - Du 16 septembre au 11 novembre 1789. Paris : Librairie Administrative P. Dupont, 1877. pp. 343-346

Discussion sur la réponse du Roi, lors de la séance du 5 octobre 1789

Goupil de Préfeln Guillaume François, Mirabeau André Boniface Louis Riqueti, vicomte de, Virieu François-Henri, comte de, Pétion de Villeneuve Jérome, Grégoire Baptiste Henri, Abbé, Maury Jean Siffrein, abbé, Monspey Louis Alexandre, marquis de, La Luzerne César Guillaume de, Camus Armand Gaston, Richier Jacques Raymond de, Coulmiers François Simmonet de, Montboissier Phillipe Claude, comte de, Mirabeau Honoré-Gabriel Riquetti, comte de, Ulry Augustin, Chasset Charles Antoine, Barrère de Vieuzac Bertrand, Bouche Charles-François, Robespierre Maximilien, Muguet de Nanthou François Felix, Duport Adrien Jean, Lameth Charles Malo, comte de, Prieur (de la Marne), Mounier Jean-Joseph, Toulongeon Hippolyte-Jean-René, marquis de. Discussion sur la réponse du Roi, lors de la séance du 5 octobre 1789. In: Archives Parlementaires de 1787 à 1860 - Première série (1787-1799) Tome IX - Du 16 septembre au 11 novembre 1789. Paris : Librairie Administrative P. Dupont, 1877. pp. 343-346