Clinical Risk Score to Predict Pathogenic Genotypes in Patients With Dilated Cardiomyopathy
Por:
Escobar-Lopez, L, Ochoa, JP, Royuela, A, Verdonschot, JAJ, Dal Ferro, M, Espinosa, MA, Sabater-Molina, M, Gallego-Delgado, M, Larranaga-Moreira, JM, Garcia-Pinilla, JM, Basurte-Elorz, MT, Rodriguez-Palomares, JF, Climent, V, Bermudez-Jimenez, FJ, Mogollon-Jimenez, MV, Lopez, J, Pena-Pena, ML, Garcia-Alvarez, A, Lopez-Abel, B, Ripoll-Vera, T, Palomino-Doza, J, Bayes-Genis, A, Brugada, R, Idiazabal, U, Mirelis, JG, Dominguez, F, Henkens, MTHM, Krapels, IPC, Brunner, HG, Paldino, A, Zaffalon, D, Mestroni, L, Sinagra, G, Heymans, SRB, Merlo, M and Garcia-Pavia, P
Publicada:
20 sep 2022
Ahead of Print:
1 sep 2022
Resumen:
BACKGROUND Although genotyping allows family screening and influences risk-stratification in patients with nonischemic dilated cardiomyopathy (DCM) or isolated left ventricular systolic dysfunction (LVSD), its result is negative in a significant number of patients, limiting its widespread adoption.OBJECTIVES This study sought to develop and externally validate a score that predicts the probability for a positive genetic test result (G+) in DCM/LVSD.METHODS Clinical, electrocardiogram, and echocardiographic variables were collected in 1,015 genotyped patients from Spain with DCM/LVSD. Multivariable logistic regression analysis was used to identify variables independently predicting G+, which were summed to create the Madrid Genotype Score. The external validation sample comprised 1,097 genotyped patients from the Maastricht and Trieste registries.RESULTS A G+ result was found in 377 (37%) and 289 (26%) patients from the derivation and validation cohorts, respectively. Independent predictors of a G+ result in the derivation cohort were: family history of DCM (OR: 2.29; 95% CI: 1.73-3.04; P < 0.001), low electrocardiogram voltage in peripheral leads (OR: 3.61; 95% CI: 2.38-5.49; P < 0.001), skeletal myopathy (OR: 3.42; 95% CI: 1.60-7.31; P = 0.001), absence of hypertension (OR: 2.28; 95% CI: 1.67-3.13; P < 0.001), and absence of left bundle branch block (OR: 3.58; 95% CI: 2.57-5.01; P < 0.001). A score containing these factors predicted a G+ result, ranging from 3% when all predictors were absent to 79% when $4 predictors were present. Internal validation provided a C-statistic of 0.74 (95% CI: 0.71-0.77) and a calibration slope of 0.94 (95% CI: 0.80-1.10). The C-statistic in the external validation cohort was 0.74 (95% CI: 0.71-0.78). CONCLUSIONS The Madrid Genotype Score is an accurate tool to predict a G+ result in DCM/LVSD. (J Am Coll Cardiol 2022;80:1115-1126)(c) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
Filiaciones:
Escobar-Lopez, L:
Hosp Univ Puerta de Hierro, Dept Cardiol, Heart Failure & Inherited Cardiac Dis Unit, IDIPHISA, Madrid, Spain
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
European Reference Network Rare & Low Prevalence, Madrid, Spain
Ochoa, JP:
Hosp Univ Puerta de Hierro, Dept Cardiol, Heart Failure & Inherited Cardiac Dis Unit, IDIPHISA, Madrid, Spain
European Reference Network Rare & Low Prevalence, Madrid, Spain
Royuela, A:
CIBERESP, Puerta de Hierro Biomed Res Inst IDIPHISA, Biostat Unit, Madrid, Spain
Verdonschot, JAJ:
Maastricht Univ, Med Ctr, Dept Clin Genet, Maastricht, Netherlands
Dal Ferro, M:
European Reference Network Rare & Low Prevalence, Madrid, Spain
Univ Trieste, ASUGI, Cardiothoracovasc Dept, Trieste, Italy
Espinosa, MA:
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Hosp Gen Univ Gregorio Maranon, Dept Cardiol, Madrid, Spain
Sabater-Molina, M:
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
European Reference Network Rare & Low Prevalence, Madrid, Spain
Univ Hosp Virgen de la Arrixaca, Inherited Cardiac Dis Unit, Murcia, Spain
Gallego-Delgado, M:
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Complejo Asistencial Univ Salamanca, Gerencia Reg Salud Castilla & Leon SACYL, Inst Invest Biomed Salamanca IBSAL, Inherited Cardiac Dis Unit,Dept Cardiol, Salamanca, Spain
Larranaga-Moreira, JM:
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Univ A Coruna, Serv Galego Saude SERGAS, Complexo Hosp Univ A Coruna, Inherited Cardiac Dis Unit,Inst Invest Biomed A C, La Coruna, Spain
Hosp Univ Virgen de la Victoria, Heart Failure & Familial Heart Dis Unit, Dept Cardiol, IBIMA, Malaga, Spain
Garcia-Pinilla, JM:
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Basurte-Elorz, MT:
Hosp Univ Navarra, Area Corazon, Dept Cardiol, Pamplona, Spain
Rodriguez-Palomares, JF:
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Univ Autonoma Barcelona, Vall dHebron Inst Recerca VHIR, Hosp Univ Vall dHebron, Inherited Cardiovasc Dis Unit,Dept Cardiol, Barcelona, Spain
Climent, V:
Hosp Gen Univ Alicante, Inst Hlth & Biomed Res, Dept Cardiol, Inherited Cardiovasc Dis Unit, Alicante, Spain
Bermudez-Jimenez, FJ:
Hosp Univ Virgen de las Nieves, Dept Cardiol, Granada, Spain
Mogollon-Jimenez, MV:
Complejo Hosp Univ Caceres, Dept Cardiol, Caceres, Spain
Lopez, J:
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Hosp Clin Univ Valladolid, Inst Ciencias Corazon ICICOR, Dept Cardiol, Valladolid, Spain
Pena-Pena, ML:
Hosp Univ Virgen del Rocio, Inherited Cardiac Dis Unit, Seville, Spain
Garcia-Alvarez, A:
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Univ Barcelona, Dept Cardiol, IDIBAPS, Hosp Clin, Barcelona, Spain
CNIC, Madrid, Spain
Lopez-Abel, B:
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Complexo Hosp Univ Santiago de Compostela, Dept Cardiol, Inherited Cardiac Dis Unit, Santiago De Compostela, Spain
Ripoll-Vera, T:
Hosp Univ Son Llatzer, Dept Cardiol, Inherited Cardiac Dis Unit, Palma De Mallorca, Spain
IdISBa, Palma De Mallorca, Spain
Palomino-Doza, J:
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Hosp Univ 12 Octubre, Dept Cardiol, Inherited Cardiac Dis Unit, Inst Invest I 12, Madrid, Spain
:
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Hosp Badalona Germans Trias & Pujol, Heart Inst, Barcelona, Spain
Brugada, R:
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
Hosp Univ Dr Josep Trueta, Dept Cardiol, Inherited Cardiac Dis Unit, Girona, Spain
Idiazabal, U:
Clin San Miguel, Dept Cardiol, Pamplona, Spain
Mirelis, JG:
Hosp Univ Puerta de Hierro, Dept Cardiol, Heart Failure & Inherited Cardiac Dis Unit, IDIPHISA, Madrid, Spain
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
European Reference Network Rare & Low Prevalence, Madrid, Spain
Dominguez, F:
Hosp Univ Puerta de Hierro, Dept Cardiol, Heart Failure & Inherited Cardiac Dis Unit, IDIPHISA, Madrid, Spain
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
European Reference Network Rare & Low Prevalence, Madrid, Spain
Henkens, MTHM:
Maastricht Univ, Med Ctr, Dept Cardiol, Maastricht, Netherlands
Krapels, IPC:
Maastricht Univ, Med Ctr, Dept Clin Genet, Maastricht, Netherlands
Brunner, HG:
Maastricht Univ, Med Ctr, Dept Clin Genet, Maastricht, Netherlands
Maastricht Univ, GROW Inst Dev Biol & Canc, Maastricht, Netherlands
Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Human Genet, Nijmegen, Netherlands
Paldino, A:
European Reference Network Rare & Low Prevalence, Madrid, Spain
Univ Trieste, ASUGI, Cardiothoracovasc Dept, Trieste, Italy
Zaffalon, D:
European Reference Network Rare & Low Prevalence, Madrid, Spain
Univ Trieste, ASUGI, Cardiothoracovasc Dept, Trieste, Italy
Mestroni, L:
Univ Colorado, CU Cardiovasc Inst, Anschutz Med Campus, Aurora, CO USA
Sinagra, G:
European Reference Network Rare & Low Prevalence, Madrid, Spain
Univ Trieste, ASUGI, Cardiothoracovasc Dept, Trieste, Italy
Heymans, SRB:
Maastricht Univ, Med Ctr, Dept Cardiol, Maastricht, Netherlands
Katholieke Univ Leuven, Dept Cardiovasc Sci, Ctr Mol & Vasc Biol, Leuven, Belgium
Merlo, M:
European Reference Network Rare & Low Prevalence, Madrid, Spain
Univ Trieste, ASUGI, Cardiothoracovasc Dept, Trieste, Italy
Garcia-Pavia, P:
Hosp Univ Puerta de Hierro, Dept Cardiol, Heart Failure & Inherited Cardiac Dis Unit, IDIPHISA, Madrid, Spain
Inst Salud Carlos III, CIBER Cardiovasc, Madrid, Spain
European Reference Network Rare & Low Prevalence, Madrid, Spain
UFV, Pozuelo De Alarcon, Spain
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