Clinical Risk Score to Predict Pathogenic Genotypes in Patients With Dilated Cardiomyopathy

Luis Escobar-Lopez, Juan Pablo Ochoa, Ana Royuela, Job A J Verdonschot, Matteo Dal Ferro, Maria Angeles Espinosa, Maria Sabater-Molina, Maria Gallego-Delgado, Jose M Larrañaga-Moreira, Jose M Garcia-Pinilla, Maria Teresa Basurte-Elorz, José F Rodríguez-Palomares, Vicente Climent, Francisco J Bermudez-Jimenez, María Victoria Mogollón-Jiménez, Javier Lopez, Maria Luisa Peña-Peña, Ana Garcia-Alvarez, Bernardo López-Abel, Tomas Ripoll-VeraJulian Palomino-Doza, Antoni Bayes-Genis, Ramon Brugada, Uxua Idiazabal, Jesus G Mirelis, Fernando Dominguez, Michiel T H M Henkens, Ingrid P C Krapels, Han G Brunner, Alessia Paldino, Denise Zaffalon, Luisa Mestroni, Gianfranco Sinagra, Stephane R B Heymans, Marco Merlo, Pablo Garcia-Pavia*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1115-1126
Number of pages12
JournalJournal of the American College of Cardiology
Volume80
Issue number12
DOIs
Publication statusPublished - 20 Sept 2022

Keywords

  • Cardiomyopathy, Dilated/diagnosis
  • Cohort Studies
  • Genotype
  • Humans
  • Risk Factors
  • Ventricular Dysfunction, Left

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