Luis Escobar-Lopez1, Juan Pablo Ochoa2, Jesús G Mirelis1, María Ángeles Espinosa3, Marina Navarro4, María Gallego-Delgado5, Roberto Barriales-Villa6, Ainhoa Robles-Mezcua7, María Teresa Basurte-Elorz8, Laura Gutiérrez García-Moreno9, Vicente Climent10, Juan Jiménez-Jaimez11, María Victoria Mogollón-Jiménez12, Javier Lopez13, María Luisa Peña-Peña14, Ana García-Álvarez15, María Brion16, Tomas Ripoll-Vera17, Julián Palomino-Doza18, Coloma Tirón19, Uxua Idiazabal20, Maria Noël Brögger21, Soledad García-Hernández22, María Alejandra Restrepo-Córdoba1, Esther Gonzalez-Lopez1, Irene Méndez3, María Sabater4, Eduardo Villacorta23, José M Larrañaga-Moreira6, Ana Abecia8, Ana Isabel Fernández3, José M García-Pinilla7, José F Rodríguez-Palomares9, Juan Ramón Gimeno-Blanes4, Antoni Bayes-Genis24, Enrique Lara-Pezzi25, Fernando Domínguez26, Pablo Garcia-Pavia27. 1. Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, Amsterdam, the Netherlands. 2. Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, Amsterdam, the Netherlands; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. 3. CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Department of Cardiology, Hospital General Universitario Gregorio Marañón, Madrid, Spain. 4. CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, Amsterdam, the Netherlands; Inherited Cardiac Disease Unit, University Hospital Virgen de la Arrixaca, Murcia, Spain. 5. CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Inherited Cardiac Diseases Unit, Department of Cardiology, Instituto de Investigación Biomédica de Salamanca, Complejo Asistencial Universitario de Salamanca, Gerencia Regional de Salud de Castilla y León, Salamanca, Spain. 6. CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Inherited Cardiac Diseases Unit, Instituto de Investigación Biomédica de A Coruña, Complexo Hospitalario Universitario de A Coruña, Servizo Galego de Saúde, Universidade da Coruña, A Coruña, Spain. 7. CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Heart Failure and Familial Heart Diseases Unit, Cardiology Department, Hospital Universitario Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga, Málaga, Spain. 8. Department of Cardiology, Área del Corazón, Complejo Hospitalario de Navarra, Pamplona, Spain. 9. CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Inherited Cardiovascular Diseases Unit, Department of Cardiology, Hospital Universitari Vall d´Hebron, Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona, Barcelona, Spain. 10. Inherited Cardiovascular Diseases Unit, Department of Cardiology, Hospital General Universitario de Alicante, Institute of Health and Biomedical Research, Alicante, Spain. 11. Department of Cardiology, Hospital Universitario Virgen de las Nieves, Granada, Spain. 12. Department of Cardiology, Complejo Hospitalario Universitario de Cáceres, Cáceres, Spain. 13. CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Department of Cardiology, Instituto de Ciencias del Corazón, Hospital Clínico Universitario Valladolid, Valladolid, Spain. 14. Inherited Cardiac Diseases Unit, Hospital Universitario Virgen del Rocío, Seville, Spain. 15. CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain; August Pi i Sunyer Biomedical Research Institute, Hospital Clínic, Departament of Medicine, Universitat de Barcelona, Barcelona, Spain. 16. CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Xenética Cardiovascular, Instituto de investigación Sanitaria de Santiago, Unidad de Cardiopatías Familiares, Department of Cardiology, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain. 17. Inherited Cardiac Diseases Unit, Cardiology Department, Hospital Universitario Son Llatzer and Institut d'Investigaciò Sanitària Illes Balears, Palma de Mallorca, Spain. 18. CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Inherited Cardiac Diseases Unit, Cardiology Department, Hospital Universitario 12 de Octubre, Instituto de Investigación i+12, Madrid, Spain. 19. Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitari Dr. Josep Trueta, Girona, Spain. 20. Depatment of Cadiology, Clinica San Miguel, Pamplona, Spain. 21. Department of Cardiology, Health in Code, A Coruña, Spain. 22. Inherited Cardiac Diseases Unit, Instituto de Investigación Biomédica de A Coruña, Complexo Hospitalario Universitario de A Coruña, Servizo Galego de Saúde, Universidade da Coruña, A Coruña, Spain; Department of Cardiology, Health in Code, A Coruña, Spain. 23. CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Inherited Cardiac Diseases Unit, Department of Cardiology, Instituto de Investigación Biomédica de Salamanca, Complejo Asistencial Universitario de Salamanca, Gerencia Regional de Salud de Castilla y León, Salamanca, Spain; Departament of Medicine, Facultad de Medicina, Universidad de Salamanca, Salamanca, Spain. 24. Heart Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. 25. CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. 26. Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, Amsterdam, the Netherlands; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain. Electronic address: fdominguezrodriguez@gmail.com. 27. Heart Failure and Inherited Cardiac Diseases Unit, Department of Cardiology, Hospital Universitario Puerta de Hierro, Madrid, Spain; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain; European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart, Amsterdam, the Netherlands; Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain; Universidad Francisco de Vitoria, Pozuelo de Alarcón, Spain. Electronic address: pablogpavia@yahoo.es.
Abstract
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: 1.09-2.07; 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.
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: 1.09-2.07; 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.
Authors: Daniel Reichart; Eric L Lindberg; Henrike Maatz; Hendrik Milting; Michela Noseda; Gavin Y Oudit; Matthias Heinig; Jonathan G Seidman; Norbert Hubner; Christine E Seidman; Antonio M A Miranda; Anissa Viveiros; Nikolay Shvetsov; Anna Gärtner; Emily R Nadelmann; Michael Lee; Kazumasa Kanemaru; Jorge Ruiz-Orera; Viktoria Strohmenger; Daniel M DeLaughter; Giannino Patone; Hao Zhang; Andrew Woehler; Christoph Lippert; Yuri Kim; Eleonora Adami; Joshua M Gorham; Sam N Barnett; Kemar Brown; Rachel J Buchan; Rasheda A Chowdhury; Chrystalla Constantinou; James Cranley; Leanne E Felkin; Henrik Fox; Ahla Ghauri; Jan Gummert; Masatoshi Kanda; Ruoyan Li; Lukas Mach; Barbara McDonough; Sara Samari; Farnoush Shahriaran; Clarence Yapp; Caroline Stanasiuk; Pantazis I Theotokis; Fabian J Theis; Antoon van den Bogaerdt; Hiroko Wakimoto; James S Ware; Catherine L Worth; Paul J R Barton; Young-Ae Lee; Sarah A Teichmann Journal: Science Date: 2022-08-05 Impact factor: 63.714
Authors: Anna Chiara Valenti; Alessandro Albini; Jacopo Francesco Imberti; Marco Vitolo; Niccolò Bonini; Giovanna Lattanzi; Renate B Schnabel; Giuseppe Boriani Journal: Biology (Basel) Date: 2022-03-30
Authors: Kevin Willy; Julia Köbe; Florian Reinke; Benjamin Rath; Christian Ellermann; Julian Wolfes; Felix K Wegner; Patrick R Leitz; Philipp S Lange; Lars Eckardt; Gerrit Frommeyer Journal: J Pers Med Date: 2022-07-28
Authors: Jesús G Mirelis; Luis Escobar-Lopez; Juan Pablo Ochoa; María Ángeles Espinosa; Eduardo Villacorta; Marina Navarro; Guillem Casas; Nerea Mora-Ayestarán; Roberto Barriales-Villa; María Victoria Mogollón-Jiménez; José M García-Pinilla; Pablo E García-Granja; Vicente Climent; Julian Palomino-Doza; Ana García-Álvarez; María Álvarez-Barredo; Eva Cabrera-Borrego; Tomás Ripoll-Vera; María Luisa Peña-Peña; Elena Rodríguez-González; María Gallego-Delgado; Josefa Gonzalez-Carrillo; Ana Fernández-Ávila; José F Rodríguez-Palomares; Ramón Brugada; Antoni Bayes-Genis; Fernando Dominguez; Pablo García-Pavía Journal: Eur J Heart Fail Date: 2022-05-22 Impact factor: 17.349