Clinical Features and Natural History of PRKAG2 Variant Cardiac Glycogenosis.
AMP-Activated Protein Kinases
/ genetics
Adolescent
Adult
Cardiomyopathies
/ diagnosis
Child
DNA
/ genetics
DNA Mutational Analysis
Echocardiography
Electrocardiography
Female
Follow-Up Studies
Glycogen Storage Disease
/ diagnosis
Humans
Male
Middle Aged
Mutation
Myocardium
/ metabolism
Phenotype
Retrospective Studies
Young Adult
PRKAG2
glycogen-storage disease
heart failure
hypertrophic cardiomyopathy
left ventricular hypertrophy
pacemaker
pre-excitation
sudden cardiac death
Journal
Journal of the American College of Cardiology
ISSN: 1558-3597
Titre abrégé: J Am Coll Cardiol
Pays: United States
ID NLM: 8301365
Informations de publication
Date de publication:
14 07 2020
14 07 2020
Historique:
received:
23
01
2020
revised:
11
05
2020
accepted:
13
05
2020
entrez:
11
7
2020
pubmed:
11
7
2020
medline:
13
1
2021
Statut:
ppublish
Résumé
PRKAG2 gene variants cause a syndrome characterized by cardiomyopathy, conduction disease, and ventricular pre-excitation. Only a small number of cases have been reported to date, and the natural history of the disease is poorly understood. The aim of this study was to describe phenotype and natural history of PRKAG2 variants in a large multicenter European cohort. Clinical, electrocardiographic, and echocardiographic data from 90 subjects with PRKAG2 variants (53% men; median age 33 years; interquartile range [IQR]: 15 to 50 years) recruited from 27 centers were retrospectively studied. At first evaluation, 93% of patients were in New York Heart Association functional class I or II. Maximum left ventricular wall thickness was 18 ± 8 mm, and left ventricular ejection fraction was 61 ± 12%. Left ventricular hypertrophy (LVH) was present in 60 subjects (67%) at baseline. Thirty patients (33%) had ventricular pre-excitation or had undergone accessory pathway ablation; 17 (19%) had pacemakers (median age at implantation 36 years; IQR: 27 to 46 years), and 16 (18%) had atrial fibrillation (median age 43 years; IQR: 31 to 54 years). After a median follow-up period of 6 years (IQR: 2.3 to 13.9 years), 71% of subjects had LVH, 29% had AF, 21% required de novo pacemakers (median age at implantation 37 years; IQR: 29 to 48 years), 14% required admission for heart failure, 8% experienced sudden cardiac death or equivalent, 4% required heart transplantation, and 13% died. PRKAG2 syndrome is a progressive cardiomyopathy characterized by high rates of atrial fibrillation, conduction disease, advanced heart failure, and life-threatening arrhythmias. Classical features of pre-excitation and severe LVH are not uniformly present, and diagnosis should be considered in patients with LVH who develop atrial fibrillation or require permanent pacemakers at a young age.
Sections du résumé
BACKGROUND
PRKAG2 gene variants cause a syndrome characterized by cardiomyopathy, conduction disease, and ventricular pre-excitation. Only a small number of cases have been reported to date, and the natural history of the disease is poorly understood.
OBJECTIVES
The aim of this study was to describe phenotype and natural history of PRKAG2 variants in a large multicenter European cohort.
METHODS
Clinical, electrocardiographic, and echocardiographic data from 90 subjects with PRKAG2 variants (53% men; median age 33 years; interquartile range [IQR]: 15 to 50 years) recruited from 27 centers were retrospectively studied.
RESULTS
At first evaluation, 93% of patients were in New York Heart Association functional class I or II. Maximum left ventricular wall thickness was 18 ± 8 mm, and left ventricular ejection fraction was 61 ± 12%. Left ventricular hypertrophy (LVH) was present in 60 subjects (67%) at baseline. Thirty patients (33%) had ventricular pre-excitation or had undergone accessory pathway ablation; 17 (19%) had pacemakers (median age at implantation 36 years; IQR: 27 to 46 years), and 16 (18%) had atrial fibrillation (median age 43 years; IQR: 31 to 54 years). After a median follow-up period of 6 years (IQR: 2.3 to 13.9 years), 71% of subjects had LVH, 29% had AF, 21% required de novo pacemakers (median age at implantation 37 years; IQR: 29 to 48 years), 14% required admission for heart failure, 8% experienced sudden cardiac death or equivalent, 4% required heart transplantation, and 13% died.
CONCLUSIONS
PRKAG2 syndrome is a progressive cardiomyopathy characterized by high rates of atrial fibrillation, conduction disease, advanced heart failure, and life-threatening arrhythmias. Classical features of pre-excitation and severe LVH are not uniformly present, and diagnosis should be considered in patients with LVH who develop atrial fibrillation or require permanent pacemakers at a young age.
Identifiants
pubmed: 32646569
pii: S0735-1097(20)35324-9
doi: 10.1016/j.jacc.2020.05.029
pii:
doi:
Substances chimiques
DNA
9007-49-2
PRKAG2 protein, human
EC 2.7.11.1
AMP-Activated Protein Kinases
EC 2.7.11.31
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
186-197Subventions
Organisme : Department of Health
ID : HICF-R6-373
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T005181/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U120085815
Pays : United Kingdom
Organisme : British Heart Foundation
ID : SP/10/10/28431
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/T024062/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 107469/Z/15/
Pays : United Kingdom
Investigateurs
Torsten B Rasmussen
(TB)
Morten K Jensen
(MK)
Roberto Barriales
(R)
Jose María Larrañaga-Moreira
(JM)
Diego Alonso-García
(D)
Ivonne Johana Cárdenas-Reyes
(IJ)
Marcos Cicerchia
(M)
German García-Ferro
(G)
Soledad García-Hernández
(S)
Lorenzo Monserrat
(L)
María Nöel-Bröger
(M)
Juan Pablo Ochoa
(JP)
Martin Ortiz
(M)
Pedro Azevedo
(P)
Dina Bento
(D)
João Bispo
(J)
Teresa Mota
(T)
Raquel Fernandes
(R)
Hugo Costa
(H)
Nuno Marques
(N)
Vicente Climent
(V)
Maria I García-Álvarez
(MI)
Sergi Cesar
(S)
Georgia Sarquella-Brugada
(G)
Alison R Muir
(AR)
Laura Pezzoli
(L)
Giovanni Quarta
(G)
Adrian Fernandez
(A)
Ella Field
(E)
Juan Pablo Kaski
(JP)
Olga Azevedo
(O)
Enrique Santas
(E)
Chiara Chiriatti
(C)
Iacopo Olivotto
(I)
Ramon Brugada
(R)
Oscar Campuzano
(O)
Coloma Tiron
(C)
Olga Azevedo
(O)
Julian Palomino Doza
(JP)
Rafael Salguero-Bodes
(R)
Maria Valverde-Gomez
(M)
Maria Angeles Espinosa
(MA)
Irene Mendez
(I)
Marta Cobo-Marcos
(M)
Fernando Domínguez
(F)
Luis Escobar
(L)
Pablo Garcia-Pavia
(P)
Esther González-López
(E)
Ángela López-Sainz
(Á)
Javier Segovia-Cubero
(J)
Silvia Vilches
(S)
Jose Manuel Garcia-Pinilla
(JM)
Ainhoa Robles-Mezcua
(A)
Miguel López-Garrido
(M)
Luis Morcillo Hidalgo
(LM)
Victoria Doncel Abad
(VD)
Marina Navarro
(M)
Maria Sabater-Molina
(M)
Juan Ramón Gimeno-Blanes
(JR)
Esther Zorio
(E)
Maria Luisa Peña-Peña
(ML)
Jens Mogensen
(J)
Paul J Barton
(PJ)
Stuart A Cook
(SA)
Angharad M Roberts
(AM)
James S Ware
(JS)
Michael Arad
(M)
Roy Beinart
(R)
Perry M Elliott
(PM)
Luis Rocha Lopes
(LR)
Massimiliano Lorenzini
(M)
Petros Syrris
(P)
Grażyna Truszkowska
(G)
Ewa Michalak
(E)
Rafal Ploski
(R)
Zofia Bilińska
(Z)
Folkert Asselbergs
(F)
Annette F Baas
(AF)
Dennis Dooijes
(D)
Marijke Linschoten
(M)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2020 American College of Cardiology Foundation. All rights reserved.