title: Diagnostic Approach to Unexplained Cardiac Arrest (from the FIVI-Gen Study).
abstract: Unexplained cardiac arrest (UCA) can be caused by low-penetrance genetic disorders. The aim of this cross-sectional study is to assess the usefulness of a new diagnostic protocol: Thirty-five patients were recruited from 9 Spanish centers. Electrocardiogram, echocardiogram, and coronary catheterization were used to rule out electrical or structural heart disease in all subjects. Patients underwent pharmacologic tests with epinephrine and flecainide, followed by assessment of family members using electrocardiogram and echocardiogram, and next-generation genetic sequencing to analyze 126 genes if all the other test results were negative. A firm diagnosis of channelopathy required phenotypic proof of the condition in unmasking tests, the presence of a pathogenic variant consistent with the phenotype observed, and/or co-segregation of the mutation found in a family member's phenotype. A firm diagnosis was made in 18 cases. The diagnoses were 7 Brugada syndrome, 5 catecholaminergic polymorphic ventricular tachycardia, 3 long QT syndrome, 2 early repolarization syndrome, and 1 short QT syndrome. Pharmacologic testing was the most frequent method of diagnosis. In 5 cases, the diagnosis was made based on positive genetic testing without phenotypic alterations. In conclusion, this sequential diagnostic protocol allows diagnoses to be made in approximately half of the UCA cases. These diagnoses are low clinical penetrance channelopathies. If interpreted carefully, genetic tests can be a useful tool for diagnosing UCA without a phenotype.
authors.affiliation: Cardiology Clinical Management Unit, Granada University Hospitals, Granada Institute of Biohealth Research, Granada, Spain. Electronic address: jimenez.jaimez@gmail.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Jiménez-Jáimez
authors.affiliation: Cardiology Department, La Paz University Hospital, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Peinado
authors.affiliation: Cardiology Department, La Fe University Hospital, Valencia, Spain.
authors.forename: Esther Zorio
authors.initials: EZ
authors.lastname: Grima
authors.affiliation: Cardiology Department, Gran Canaria Island Hospital, Las Palmas de Gran Canaria, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Segura
authors.affiliation: Cardiology Department, Juan Ramón Jiménez Hospital, Huelva, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Moriña
authors.affiliation: Cardiology Department, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Sánchez Muñoz
authors.affiliation: Cardiology Department, Reina Sofía University Hospital, Córdoba, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Mazuelos
authors.affiliation: Cardiology Department, Virgen de Macarena University Hospital, Seville, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Cózar
authors.affiliation: Cardiology Department, Virgen de la Arrixaca University Hospital, Murcia, Spain.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Gimeno
authors.affiliation: Cardiology Department, Virgen de Valme University Hospital, Seville, Spain.
authors.forename: Rocío P
authors.initials: RP
authors.lastname: Heras
authors.affiliation: Cardiology Department, Health in Code SL, A Coruña, Spain.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Monserrat
authors.affiliation: Cardiology Department, La Fe University Hospital, Valencia, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Domingo
authors.affiliation: Cardiology Department, Health in Code SL, A Coruña, Spain.
authors.forename: Martín
authors.initials: M
authors.lastname: Ortiz-Genga
authors.affiliation: Cardiology Department, Virgen de la Victoria University Hospital, Málaga, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Fernández Pastor
authors.affiliation: Cardiology Clinical Management Unit, Granada University Hospitals, Granada Institute of Biohealth Research, Granada, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Álvarez
authors.affiliation: Cardiology Clinical Management Unit, Granada University Hospitals, Granada Institute of Biohealth Research, Granada, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Tercedor
mesh_terms: D000293:Adolescent; D000328:Adult; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000175:diagnosis*; D053840:Brugada Syndrome / Q000150:complications / Q000175:diagnosis; D006328:Cardiac Catheterization / Q000379:methods; D002985:Clinical Protocols; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004452:Echocardiography / Q000379:methods; D004562:Electrocardiography / Q000379:methods; D004837:Epinephrine; D005190:Family; D005260:Female; D005424:Flecainide; D005820:Genetic Testing / Q000379:methods; D006323:Heart Arrest / Q000209:etiology*; D006331:Heart Diseases / Q000150:complications / Q000175:diagnosis; D006801:Humans; D008133:Long QT Syndrome / Q000150:complications / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D013566:Sympathomimetics; D017180:Tachycardia, Ventricular / Q000150:complications / Q000175:diagnosis; D055815:Young Adult; D000098850:Polymorphic Catecholaminergic Ventricular Tachycardia
chemical_list: D000889:Anti-Arrhythmia Agents; D013566:Sympathomimetics; D005424:Flecainide; D004837:Epinephrine