Association of Genetic Variants With Outcomes in Patients With Nonischemic Dilated Cardiomyopathy

被引:89
作者
Escobar-Lopez, Luis [1 ,2 ,3 ]
Ochoa, Juan Pablo [1 ,2 ,3 ,4 ]
Mirelis, Jesus G. [1 ,2 ,3 ]
Espinosa, Maria Angeles [2 ,5 ]
Navarro, Marina [2 ,3 ,6 ]
Gallego-Delgado, Maria [2 ,7 ]
Barriales-Villa, Roberto [2 ,8 ]
Robles-Mezcua, Ainhoa [2 ,9 ]
Basurte-Elorz, Maria Teresa [10 ]
Garcia-Moreno, Laura Gutierrez [2 ,11 ]
Climent, Vicente [12 ]
Jimenez-Jaimez, Juan [13 ]
Mogollon-Jimenez, Maria Victoria [14 ]
Lopez, Javier [2 ,15 ]
Pena-Pena, Maria Luisa [16 ]
Garcia-Alvarez, Ana [2 ,4 ,17 ]
Brion, Maria [2 ,18 ]
Ripoll-Vera, Tomas [19 ,20 ]
Palomino-Doza, Julian [2 ,21 ]
Tiron, Coloma [22 ]
Idiazabal, Uxua [23 ]
Brogger, Maria Noel [24 ]
Garcia-Hernandez, Soledad [8 ,24 ]
Restrepo-Cordoba, Maria Alejandra [2 ,3 ]
Gonzalez-Lopez, Esther [2 ,3 ]
Mendez, Irene [2 ,5 ]
Sabater Molina, Maria [2 ,3 ,6 ]
Villacorta, Eduardo [2 ,7 ,25 ]
Larranaga-Moreira, Jose M. [2 ,8 ]
Abecia, Ana [10 ]
Fernandez, Ana Isabel [2 ,5 ]
Garcia-Pinilla, Jose M. [2 ,9 ]
Rodriguez-Palomares, Jose F. [2 ,11 ]
Gimeno-Blanes, Juan Ramon [2 ,3 ,6 ,26 ]
Bayes-Genis, Antoni
Lara-Pezzi, Enrique [2 ,4 ]
Dominguez, Fernando [1 ,2 ,3 ,4 ]
Garcia-Pavia, Pablo [1 ,2 ,3 ,4 ,27 ]
机构
[1] Hosp Univ Puerta de Hierro, Dept Cardiol, Heart Failure & Inherited Cardiac Dis Unit, Madrid, Spain
[2] Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
[3] European Reference Network Rare & Low Prevalence, Amsterdam, Netherlands
[4] Ctr Nacl Invest Cardiovasc, Madrid, Spain
[5] Hosp Gen Univ Gregorio Maranon, Dept Cardiol, Madrid, Spain
[6] Univ Hosp Virgen de la Arrixaca, Inherited Cardiac Dis Unit, Murcia, Spain
[7] Complejo Asistencial Univ Salamanca, Inst Invest Biomed Salamanca, Inherited Cardiac Dis Unit, Dept Cardiol,Gerencia Reg Salud Castilla & Leon, Salamanca, Spain
[8] Univ A Coruna, Complexo Hosp Univ A Coruna, Inst Invest Biomed A Coruna, Inherited Cardiac Dis Unit,Serv Galedo Saude, La Coruna, Spain
[9] Hosp Univ Virgen de la Victoria, Heart Failure & Familial Heart Dis Unit, Dept Cardiol, Inst Invest Biomed Malaga, Malaga, Spain
[10] Complejo Hosp Navarra, Dept Cardiol, Area Corazon, Pamplona, Spain
[11] Univ Autonoma Barcelona, Inherited Cardiovasc Dis Unit, Dept Cardiol, Vall dHebron Inst Recerca,Hosp Univ Vall dHebron, Barcelona, Spain
[12] Hosp Gen Univ Alicante, Inst Hlth & Biomed Res, Inherited Cardiovasc Dis Unit, Dept Cardiol, Alicante, Spain
[13] Hosp Univ Virgen de las Nieves, Dept Cardiol, Granada, Spain
[14] Complejo Hosp Univ Caceres, Dept Cardiol, Caceres, Spain
[15] Hosp Clin Univ Valladolid, Dept Cardiol, Inst Ciencias Corazon, Valladolid, Spain
[16] Hosp Univ Virgen del Rocio, Inherited Cardiac Dis Unit, Seville, Spain
[17] Univ Barcelona, August Pi & Sunyer Biomed Res Inst, Hosp Clin, Dept Med, Barcelona, Spain
[18] Complexo Hosp Univ Santiago de Compostela, Xenet Cardiovasc, Inst Invest Sanitaria Santiago, Unidad Cardiopatias Familiares,Dept Cardiol, Santiago De Compostela, Spain
[19] Hosp Univ Son Llatzer, Dept Cardiol, Inherited Cardiac Dis Unit, Palma De Mallorca, Spain
[20] Inst Invest Sanitaria Illes Balears, Palma De Mallorca, Spain
[21] Hosp Univ 12 Octubre, Inherited Cardiac Dis Unit, Inst Invest I 12, Dept Cardiol, Madrid, Spain
[22] Hosp Univ Dr Josep Trueta, Dept Cardiol, Inherited Cardiac Dis Unit, Girona, Spain
[23] Clin San Miguel, Dept Cardiol, Pamplona, Spain
[24] Hlth Code, Dept Cardiol, La Coruna, Spain
[25] Univ Salamanca, Fac Med, Dept Med, Salamanca, Spain
[26] Hosp Badalona Germans Trias & Pujol, Inst Heart, Badalona, Spain
[27] Univ Francisco de Vitoria, Pozuelo De Alarcon, Spain
关键词
dilated cardiomyopathy; genetics; heart failure; left ventricular reverse remodeling; mutation; prognosis; sudden cardiac death; ventricular arrhythmia; RISK; DEFIBRILLATOR; GUIDELINES; MANAGEMENT; STATEMENT;
D O I
10.1016/j.jacc.2021.08.039
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND The clinical relevance of genetic variants in nonischemic dilated cardiomyopathy (DCM) is unsettled. OBJECTIVES The study sought to assess the prognostic impact of disease-causing genetic variants in DCM. METHODS Baseline and longitudinal clinical data from 1,005 genotyped DCM probands were retrospectively collected at 20 centers. A total of 372 (37%) patients had pathogenic or likely pathogenic variants (genotype positive) and 633 (63%) were genotype negative. The primary endpoint was a composite of major adverse cardiovascular events. Secondary endpoints were end-stage heart failure (ESHF), malignant ventricular arrhythmia (MVA), and left ventricular reverse remodeling (LVRR) RESULTS After a median follow-up of 4.04 years (interquartile range: 1.70-7.50 years), the primary endpoint had occurred in 118 (31.7%) patients in the genotype-positive group and in 125 (19.8%) patients in the genotype-negative group (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.17-1.94; P = 0.001). ESHF occurred in 60 (16.1%) genotype-positive patients and in 55 (8.7%) genotype-negative patients (HR: 1.67; 95% CI: 1.16-2.41; P = 0.006). MVA occurred in 73 (19.6%) genotype-positive patients and in 77 (12.2%) genotype-negative patients (HR: 1.50; 95% CI: 1.092.07; P = 0.013). LVRR occurred in 39.6% in the genotype-positive group and in 46.2% in the genotype-negative group (P = 0.047). Among individuals with baseline left ventricular ejection fraction #35%, genotype-positive patients exhibited more major adverse cardiovascular events, ESHF, and MVA than their genotype-negative peers (all P < 0.02). LVRR and clinical outcomes varied depending on the underlying affected gene. CONCLUSIONS In this study, DCM patients with pathogenic or likely pathogenic variants had worse prognosis than genotype-negative individuals. Clinical course differed depending on the underlying affected gene. (J Am Coll Cardiol 2021;78:1682-1699) (c) 2021 by the American College of Cardiology Foundation.
引用
收藏
页码:1682 / 1699
页数:18
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