Clinical Risk Score to Predict Pathogenic Genotypes in Patients With Dilated Cardiomyopathy
Escobar-Lopez, Luis (Instituto de Salud Carlos III)
Ochoa, Juan Pablo (European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart)
Royuela, Ana (Instituto Investigación Sanitaria Puerta de Hierro)
Verdonschot, Job A.J. (Maastricht University Medical Center)
Ferro, Matteo Dal (University of Trieste)
Espinosa, Maria Angeles (Hospital General Universitario Gregorio Marañón)
Sabater-Molina, Maria (Hospital Clínico Universitario Virgen de la Arrixaca (El Palmar, Múrcia))
Gallego-Delgado, Maria (Complejo Asistencial Universitario de Salamanca)
Larrañaga-Moreira, Jose M. (Universidade da Coruña)
Garcia-Pinilla, Jose M. (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Basurte-Elorz, María Teresa (Hospital Universitario de Navarra)
Rodríguez Palomares, José F. (Vall d'Hebron Institut de Recerca (VHIR))
Climent, Vicente (Hospital General Universitario de Alicante (Alacant, País Valencià))
Bermudez Jimenez, Francisco J. (Hospital Universitario Virgen de las Nieves (Granada))
Mogollón-Jiménez, María Victoria (Complejo Hospitalario Universitario de Cáceres)
Lopez, Javier (Hospital Clínico Universitario de Valladolid)
Peña-Peña, Maria Luisa (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
García-Álvarez, Ana (Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares)
López-Abel, Bernardo (Complejo Hospitalario Universitario de Santiago de Compostela)
Ripoll-Vera, Tomás (Hospital Universitari Son Llàtzer (Palma de Mallorca, Balears))
Palomino-Doza, Julian (Hospital 12 de Octubre (Madrid))
Bayés-Genís, Antoni (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Brugada, Ramon (Hospital Universitari de Girona Doctor Josep Trueta)
Idiazabal, Uxua (Clinica San Miguel)
Mirelis, Jesus G. (Instituto de Salud Carlos III)
Dominguez, Fernando (Instituto de Salud Carlos III)
Henkens, Michiel T.H.M. (Maastricht University Medical Center)
Krapels, Ingrid P.C. (Maastricht University Medical Center)
Brunner, Han G. (Radboud University Medical Center)
Paldino, Alessia (University of Trieste)
Zaffalon, Denise (University of Trieste)
Mestroni, Luisa (University of Colorado Anschutz Medical Campus)
Sinagra, Gianfranco (University of Trieste)
Heymans, Stephane R.B. (Center for Molecular and Vascular Biology (Bèlgica))
Merlo, Marco (University of Trieste)
García-Pavia, Pablo (Universidad Francisco de Vitoria)
Universitat Autònoma de Barcelona

Date:	2022
Abstract:	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. This study sought to develop and externally validate a score that predicts the probability for a positive genetic test result (G+) in DCM/LVSD. 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. 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). The Madrid Genotype Score is an accurate tool to predict a G+ result in DCM/LVSD. (J Am Coll Cardiol 2022;80:1115-1126) © 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.
Grants:	Instituto de Salud Carlos III PI17/01941 Instituto de Salud Carlos III PI19/01283 Instituto de Salud Carlos III PI20/0320
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Dilated cardiomyopathy ; Genetic variant ; Genetics ; Genotype ; Predictor
Published in:	Journal of the American College of Cardiology, Vol. 80 (september 2022) , p. 1115-1126, ISSN 1558-3597

DOI: 10.1016/j.jacc.2022.06.040
PMID: 36109106

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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