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

来源：

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY | 2021年 / 78卷 / 17期

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

页码：1682 / 1699

页数：18

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