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

被引：108

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

共 30 条

[11] A gene-centric strategy for identifying disease-causing rare variants in dilated cardiomyopathy [J].

Horvat, Claire ;

Johnson, Renee ;

Lam, Lien ;

Munro, Jacob ;

Mazzarotto, Francesco ;

Roberts, Angharad M. ;

Herman, Daniel S. ;

Parfenov, Michael ;

Haghighi, Alireza ;

McDonough, Barbara ;

DePalma, Steven R. ;

Keogh, Anne M. ;

Macdonald, Peter S. ;

Hayward, Christopher S. ;

Roberts, Amy ;

Barton, Paul J. R. ;

Felkin, Leanne E. ;

Giannoulatou, Eleni ;

Cook, Stuart A. ;

Seidman, J. G. ;

Seidman, Christine E. ;

Fatkin, Diane .

GENETICS IN MEDICINE, 2019, 21 (01) :133-143

[12] Truncating titin mutations are associated with a mild and treatable form of dilated cardiomyopathy [J].

Jansweijer, Joeri A. ;

Nieuwhof, Karin ;

Russo, Francesco ;

Hoorntje, Edgar T. ;

Jongbloed, Jan D. H. ;

Deprez, Ronald H. Lekanne ;

Postma, Alex V. ;

Bronk, Marieke ;

van Rijsingen, Ingrid A. W. ;

de Haij, Simone ;

Biagini, Elena ;

van Haelst, Paul L. ;

van Wijngaarden, Jan ;

van den Berg, Maarten P. ;

Wilde, Arthur A. M. ;

Mannens, Marcel M. A. M. ;

de Boer, Rudolf A. ;

van Spaendonck-Zwarts, Karin Y. ;

van Tintelen, J. Peter ;

Pinto, Yigal M. .

EUROPEAN JOURNAL OF HEART FAILURE, 2017, 19 (04) :512-521

[13] The mutational constraint spectrum quantified from variation in 141,456 humans [J].

Karczewski, Konrad J. ;

Francioli, Laurent C. ;

Tiao, Grace ;

Cummings, Beryl B. ;

Alfoldi, Jessica ;

Wang, Qingbo ;

Collins, Ryan L. ;

Laricchia, Kristen M. ;

Ganna, Andrea ;

Birnbaum, Daniel P. ;

Gauthier, Laura D. ;

Brand, Harrison ;

Solomonson, Matthew ;

Watts, Nicholas A. ;

Rhodes, Daniel ;

Singer-Berk, Moriel ;

England, Eleina M. ;

Seaby, Eleanor G. ;

Kosmicki, Jack A. ;

Walters, Raymond K. ;

Tashman, Katherine ;

Farjoun, Yossi ;

Banks, Eric ;

Poterba, Timothy ;

Wang, Arcturus ;

Seed, Cotton ;

Whiffin, Nicola ;

Chong, Jessica X. ;

Samocha, Kaitlin E. ;

Pierce-Hoffman, Emma ;

Zappala, Zachary ;

O'Donnell-Luria, Anne H. ;

Minikel, Eric Vallabh ;

Weisburd, Ben ;

Lek, Monkol ;

Ware, James S. ;

Vittal, Christopher ;

Armean, Irina M. ;

Bergelson, Louis ;

Cibulskis, Kristian ;

Connolly, Kristen M. ;

Covarrubias, Miguel ;

Donnelly, Stacey ;

Ferriera, Steven ;

Gabriel, Stacey ;

Gentry, Jeff ;

Gupta, Namrata ;

Jeandet, Thibault ;

Kaplan, Diane ;

Llanwarne, Christopher .

NATURE, 2020, 581 (7809) :434-+

[14] Defibrillator Implantation in Patients with Nonischemic Systolic Heart Failure [J].

Kober, Lars ;

Thune, Jens J. ;

Nielsen, Jens C. ;

Haarbo, Jens ;

Videbaek, Lars ;

Korup, Eva ;

Jensen, Gunnar ;

Hildebrandt, Per ;

Steffensen, Flemming H. ;

Bruun, Niels E. ;

Eiskjaer, Hans ;

Brandes, Axel ;

Thogersen, Anna M. ;

Gustafsson, Finn ;

Egstrup, Kenneth ;

Videbaek, Regitze ;

Hassager, Christian ;

Svendsen, Jesper H. ;

Hofsten, Dan E. ;

Torp-Pedersen, Christian ;

Pehrson, Steen .

NEW ENGLAND JOURNAL OF MEDICINE, 2016, 375 (13) :1221-1230

[15] Long-Term Arrhythmic and Nonarrhythmic Outcomes of Lamin A/C Mutation Carriers [J].

Kumar, Saurabh ;

Baldinger, Samuel H. ;

Gandjbakhch, Estelle ;

Maury, Philippe ;

Sellal, Jean-Marc ;

Androulakis, Alexander F. A. ;

Waintraub, Xavier ;

Charron, Philippe ;

Rollin, Anne ;

Richard, Pascale ;

Stevenson, William G. ;

Macintyre, Ciorsti J. ;

Ho, Carolyn Y. ;

Thompson, Tina ;

Vohra, Jitendra K. ;

Kalman, Jonathan M. ;

Zeppenfeld, Katja ;

Sacher, Frederic ;

Tedrow, Usha B. ;

Lakdawala, Neal K. .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2016, 68 (21) :2299-2307

[16] Closing the Genotype-Phenotype Loop for Precision Medicine [J].

MacRae, Calum A. ;

Seidman, Christine E. .

CIRCULATION, 2017, 136 (16) :1492-1494

[17] Epidemiology of the inherited cardiomyopathies [J].

McKenna, William J. ;

Judge, Daniel P. .

NATURE REVIEWS CARDIOLOGY, 2021, 18 (01) :22-36

[18] Dilated Cardiomyopathy: A Paradigm of Revolution in Medicine [J].

Merlo, Marco ;

Cannata, Antonio ;

Sinagra, Gianfranco .

JOURNAL OF CLINICAL MEDICINE, 2020, 9 (11)

[19] Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases [J].

Pinto, Yigal M. ;

Elliott, Perry M. ;

Arbustini, Eloisa ;

Adler, Yehuda ;

Anastasakis, Aris ;

Boehm, Michael ;

Duboc, Denis ;

Gimeno, Juan ;

de Groote, Pascal ;

Imazio, Massimo ;

Heymans, Stephane ;

Klingel, Karin ;

Komajda, Michel ;

Limongelli, Giuseppe ;

Linhart, Ales ;

Mogensen, Jens ;

Moon, James ;

Pieper, Petronella G. ;

Seferovic, Petar M. ;

Schueler, Stephan ;

Zamorano, Jose L. ;

Caforio, Alida L. P. ;

Charron, Philippe .

EUROPEAN HEART JOURNAL, 2016, 37 (23) :1850-1858

[20] 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure [J].

Ponikowski, Piotr ;

Voors, Adriaan A. ;

Anker, Stefan D. ;

Bueno, Hector ;

Cleland, John G. F. ;

Coats, Andrew J. S. ;

Falk, Volkmar ;

Ramon Gonzalez-Juanatey, Jose ;

Harjola, Veli-Pekka ;

Jankowska, Ewa A. ;

Jessup, Mariell ;

Linde, Cecilia ;

Nihoyannopoulos, Petros ;

Parissis, John T. ;

Pieske, Burkert ;

Riley, Jillian P. ;

Rosano, Giuseppe M. C. ;

Ruilope, Luis M. ;

Ruschitzka, Frank ;

Rutten, Frans H. ;

van der Meer, Peter .

EUROPEAN HEART JOURNAL, 2016, 37 (27) :2129-U130

← 1 2 3 →