Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives.
J Am Coll Cardiol
; 83(17): 1640-1651, 2024 Apr 30.
Article
em En
| MEDLINE
| ID: mdl-38658103
ABSTRACT
BACKGROUND:
Disease penetrance in genotype-positive (G+) relatives of families with dilated cardiomyopathy (DCM) and the characteristics associated with DCM onset in these individuals are unknown.OBJECTIVES:
This study sought to determine the penetrance of new DCM diagnosis in G+ relatives and to identify factors associated with DCM development.METHODS:
The authors evaluated 779 G+ patients (age 35.8 ± 17.3 years; 459 [59%] females; 367 [47%] with variants in TTN) without DCM followed at 25 Spanish centers.RESULTS:
After a median follow-up of 37.1 months (Q1-Q3 16.3-63.8 months), 85 individuals (10.9%) developed DCM (incidence rate of 2.9 per 100 person-years; 95% CI 2.3-3.5 per 100 person-years). DCM penetrance and age at DCM onset was different according to underlying gene group (log-rank P = 0.015 and P <0.01, respectively). In a multivariable model excluding CMR parameters, independent predictors of DCM development were older age (HR per 1-year increase 1.02; 95% CI 1.0-1.04), an abnormal electrocardiogram (HR 2.13; 95% CI 1.38-3.29); presence of variants in motor sarcomeric genes (HR 1.92; 95% CI 1.05-3.50); lower left ventricular ejection fraction (HR per 1% increase 0.86; 95% CI 0.82-0.90) and larger left ventricular end-diastolic diameter (HR per 1-mm increase 1.10; 95% CI 1.06-1.13). Multivariable analysis in individuals with cardiac magnetic resonance and late gadolinium enhancement assessment (n = 360, 45%) identified late gadolinium enhancement as an additional independent predictor of DCM development (HR 2.52; 95% CI 1.43-4.45).CONCLUSIONS:
Following a first negative screening, approximately 11% of G+ relatives developed DCM during a median follow-up of 3 years. Older age, an abnormal electrocardiogram, lower left ventricular ejection fraction, increased left ventricular end-diastolic diameter, motor sarcomeric genetic variants, and late gadolinium enhancement are associated with a higher risk of developing DCM.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Cardiomiopatia Dilatada
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Penetrância
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Genótipo
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
País como assunto:
Europa
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article