RESUMEN
The genetic causes of atrial fibrillation (AF) with slow conduction are unknown. Eight kindreds with familial AF and slow conduction, including a family affected by early-onset AF, heart block, and incompletely penetrant nonischemic dilated cardiomyopathy (DCM) underwent whole exome sequencing. A known pathogenic mutation in the desmin (DES) gene resulting in p.S13F substitution (NM_001927.3:c.38C>T) at a PKC phosphorylation site was identified in all four members of the kindred with early-onset AF and heart block, while only two developed DCM. Higher penetrance for AF and heart block prompted a genetic screening for DES modifier(s). A deleterious mutation in the phosphodiesterase-4D-interacting-protein (PDE4DIP) gene resulting in p.A123T substitution (NM_001002811:c.367G>A) was identified that segregated with early-onset AF, heart block, and the DES mutation. Three additional novel deleterious PDE4DIP mutations were identified in four other unrelated kindreds. Characterization of PDE4DIPA123T in vitro suggested impaired compartmentalization of PKA and PDE4D characterized by reduced colocalization with PDE4D, increased cAMP activation leading to higher PKA phosphorylation of the ß2-adrenergic-receptor, and decreased PKA phosphorylation of desmin after isoproterenol stimulation. Our findings identify PDE4DIP as a novel gene for slow AF and unravel its epistatic interaction with DES mutations in development of conduction disease and arrhythmia.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Fibrilación Atrial , Cardiomiopatía Dilatada , Proteínas del Citoesqueleto/genética , Desmina/genética , Fibrilación Atrial/genética , Cardiomiopatía Dilatada/genética , Humanos , Mutación , Penetrancia , Secuenciación del ExomaAsunto(s)
Antivirales/efectos adversos , Arritmias Cardíacas/inducido químicamente , Infecciones por Coronavirus/tratamiento farmacológico , Frecuencia Cardíaca/efectos de los fármacos , Hidroxicloroquina/efectos adversos , Neumonía Viral/tratamiento farmacológico , Potenciales de Acción/efectos de los fármacos , Anciano , Antivirales/farmacocinética , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatología , COVID-19 , Cardiotoxicidad , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/virología , Femenino , Humanos , Hidroxicloroquina/farmacocinética , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Tratamiento Farmacológico de COVID-19RESUMEN
We present a case of post herpetic neuralgia in a patient admitted with a prior herpetic infection complicated by recurrent episodes of asystole and cardiac arrest. We first tried medical therapy with the use of high doses of intravenous analgesics, opiates, carbamazepine and phenytoin. However, the high recurrence rate of the pain episodes with concomitant cardiac arrest and cardiopulmonary resuscitation warranted first the placement of a temporary pacing lead, and shortly after a permanent device as a rescue procedure. This case illustrates the treatment difficulties in such an uncommon and extreme situation.
Asunto(s)
Paro Cardíaco/etiología , Herpes Zóster/complicaciones , Neuralgia Posherpética/complicaciones , Anciano , Analgésicos Opioides/administración & dosificación , Reanimación Cardiopulmonar/métodos , Femenino , HumanosRESUMEN
Breath-holding spells (BHS) are frequent and benign in children. Medical treatment is rarely needed but exceptionally severe forms require the implantation of a pacemaker. We describe here the case of an 18-month-old girl who presented to our department with severe episodes of BHS associated with loss of consciousness. This child necessitated the insertion of a pacemaker, which resolved her BHS.
