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Relationship Between Genotype Status and Clinical Outcome in Hypertrophic Cardiomyopathy.
Bonaventura, Jiri; Rowin, Ethan J; Chan, Raymond H; Chin, Michael T; Puchnerova, Veronika; Polakova, Eva; Macek, Milan; Votypka, Pavel; Batorsky, Rebecca; Perera, Gayani; Koethe, Benjamin; Veselka, Josef; Maron, Barry J; Maron, Martin S.
Afiliación
  • Bonaventura J; Department of Cardiology, 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic.
  • Rowin EJ; Hypertrophic Cardiomyopathy Center Lahey Hospital and Medical Center Burlington MA USA.
  • Chan RH; Hypertrophic Cardiomyopathy Center Lahey Hospital and Medical Center Burlington MA USA.
  • Chin MT; Division of Cardiology, Peter Munk Cardiac Centre Toronto General Hospital, University Health Network Ontario Canada.
  • Puchnerova V; Molecular Cardiology Research Institute Tufts Medical Center Boston MA USA.
  • Polakova E; Department of Cardiology, 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic.
  • Macek M; Department of Cardiology, 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic.
  • Votypka P; Department of Biology and Medical Genetics, 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic.
  • Batorsky R; Department of Biology and Medical Genetics, 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic.
  • Perera G; Molecular Cardiology Research Institute Tufts Medical Center Boston MA USA.
  • Koethe B; Molecular Cardiology Research Institute Tufts Medical Center Boston MA USA.
  • Veselka J; Institute for Clinical Research and Health Policy Studies, Tufts Medical Center Boston MA USA.
  • Maron BJ; Department of Cardiology, 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czech Republic.
  • Maron MS; Hypertrophic Cardiomyopathy Center Lahey Hospital and Medical Center Burlington MA USA.
J Am Heart Assoc ; 13(10): e033565, 2024 May 21.
Article en En | MEDLINE | ID: mdl-38757491
ABSTRACT

BACKGROUND:

The genetic basis of hypertrophic cardiomyopathy (HCM) is complex, and the relationship between genotype status and clinical outcome is incompletely resolved. METHODS AND

RESULTS:

We assessed a large international HCM cohort to define in contemporary terms natural history and clinical consequences of genotype. Consecutive patients (n=1468) with established HCM diagnosis underwent genetic testing. Patients with pathogenic (or likely pathogenic) variants were considered genotype positive (G+; n=312; 21%); those without definite disease-causing mutations (n=651; 44%) or variants of uncertain significance (n=505; 35%) were considered genotype negative (G-). Patients were followed up for a median of 7.8 years (interquartile range, 3.5-13.4 years); HCM end points were examined by cumulative event incidence. Over follow-up, 135 (9%) patients died, 33 from a variety of HCM-related causes. After adjusting for age, all-cause and HCM-related mortality did not differ between G- versus G+ patients (hazard ratio [HR], 0.78 [95% CI, 0.46-1.31]; P=0.37; HR, 0.93 [95% CI, 0.38-2.30]; P=0.87, respectively). Adverse event rates, including heart failure progression to class III/IV, heart transplant, or heart failure death, did not differ (G- versus G+) when adjusted for age (HR, 1.20 [95% CI, 0.63-2.26]; P=0.58), nor was genotype independently associated with sudden death event risk (HR, 1.39 [95% CI, 0.88-2.21]; P=0.16). In multivariable analysis, age was the only independent predictor of all-cause and HCM-related mortality, heart failure progression, and sudden death events.

CONCLUSIONS:

In this large consecutive cohort of patients with HCM, genotype (G+ or G-) was not a predictor of clinical course, including all-cause and HCM-related mortality and risk for heart failure progression or sudden death. G+ status should not be used to dictate clinical management or predict outcome in HCM.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cardiomiopatía Hipertrófica / Genotipo Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Am Heart Assoc Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cardiomiopatía Hipertrófica / Genotipo Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Am Heart Assoc Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido