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Clinical Features and Natural History of PRKAG2 Variant Cardiac Glycogenosis

2020; Elsevier BV; Volume: 76; Issue: 2 Linguagem: Inglês

10.1016/j.jacc.2020.05.029

1558-3597

Ángela López‐Sainz, Fernándo Domínguez, Luís R. Lopes, Juan Pablo Ochoa, Roberto Barriales‐Villa, Vicente Climent, Marijke Linschoten, Coloma Tirón, Chiara Chiriatti, Nuno Marques, Torsten B. Rasmussen, María Ángeles Espinosa, Roy Beinart, Giovanni Quarta, Sergi César, Ella Field, José Manuel García‐Pinilla, Zofia T. Bilińska, Alison Muir, Angharad M. Roberts, Enrique Santas, Esther Zorio, María Luisa Peña‐Peña, Marina Navarro Peñalver, Adrián Fernández, Julián Palomino-Doza, Olga Azevedo, Massimiliano Lorenzini, Ana García‐Álvarez, Dina Bento, Morten K. Jensen, Irene Méndez, Laura Pezzoli, Geòrgia Sarquella-Brugada, Óscar Campuzano, Esther González-López, Jens Mogensen, Juan Pablo Kaski, Michael Arad, Ramón Brugada, Folkert W. Asselbergs, Lorenzo Monserrat, Iacopo Olivotto, Perry Elliott, Pablo García‐Pavía, Torsten B. Rasmussen, Morten K. Jensen, Roberto Barriales‐Villa, José M. Larrañaga‐Moreira, Diego Alonso-García, Ivonne J. Cárdenas-Reyes, Marcos Cicerchia, German García-Ferro, Soledad García-Hernández, Lorenzo Monserrat, María Nöel-Bröger, Juan Pablo Ochoa, Martín Ortiz, Olga Azevedo, Dina Bento, João Bispo, Teresa Mota, Raquel Menezes Fernandes, Hugo Costa, Nuno Marques, Vicente Climent, Ana García‐Álvarez, Sergi César, Geòrgia Sarquella-Brugada, Alison Muir, Laura Pezzoli, Giovanni Quarta, Adrián Fernández, Ella Field, Juan Pablo Kaski, Olga Azevedo, Enrique Santas, Chiara Chiriatti, Iacopo Olivotto, Ramón Brugada, Óscar Campuzano, Coloma Tirón, Olga Azevedo, Julián Palomino Doza, Rafael Salguero‐Bodes, María Valverde-Gómez, María Ángeles Espinosa, Irene Méndez, Marta Cobo Marcos, Fernándo Domínguez, Luis Escobar, Pablo García‐Pavía, Esther González-López, Ángela López‐Sainz, Javier Segovia, Silvia Vilches, José Manuel García‐Pinilla, Ainhoa Robles Mezcua, Miguel A. López-Garrido, Luis Morcillo‐Hidalgo, V. Abad, Marina Navarro Peñalver, María Sabater‐Molina, Juan R. Gimeno, Esther Zorio, María Luisa Peña‐Peña, Jens Mogensen, Paul J.R. Barton, Stuart A. Cook, Angharad M. Roberts, James S. Ware, Michael Arad, Roy Beinart, Perry Elliott, Luís R. Lopes, Massimiliano Lorenzini, Petros Syrris, Grażyna Truszkowska, Ewa Michalak, Rafał Płoski, Zofia T. Bilińska, Folkert W. Asselbergs, Annette F. Baas, Dennis Dooijes, Marijke Linschoten,

Lysosomal Storage Disorders Research

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.