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Observational Study
. 2018 Mar;41(3):343-348.
doi: 10.1002/clc.22870. Epub 2018 Mar 22.

Identification of clinically relevant phenotypes in patients with Ebstein anomaly

Rodrigo Cabrera  1 , Marta Catalina Miranda-Fernández  1 , Victor Manuel Huertas-Quiñones  2   3   4 , Marisol Carreño  5 , Ivonne Pineda  5 , Carlos M Restrepo  6 , Claudia Tamar Silva  6 , Rossi Quero  6 , Juan David Cano  7 , Diana Carolina Manrique  7 , Camila Camacho  7 , Sebastián Tabares  7 , Alberto García  2   4   7   8 , Néstor Sandoval  2   4 , Karen Julieth Moreno Medina  9 , Rodolfo José Dennis Verano  9   10
Affiliations
Observational Study

Identification of clinically relevant phenotypes in patients with Ebstein anomaly

Rodrigo Cabrera et al. Clin Cardiol. 2018 Mar.

Abstract

Background: Ebstein anomaly (EA) is a heterogeneous congenital heart defect (CHD), frequently accompanied by diverse cardiac and extracardiac comorbidities, resulting in a wide range of clinical outcomes.

Hypothesis: Phenotypic characterization of EA patients has the potential to identify variables that influence prognosis and subgroups with distinct contributing factors.

Methods: A comprehensive cross-sectional phenotypic characterization of 147 EA patients from one of the main referral institutions for CHD in Colombia was carried out. The most prevalent comorbidities and distinct subgroups within the patient cohort were identified through cluster analysis.

Results: The most prevalent cardiac comorbidities identified were atrial septal defect (61%), Wolff-Parkinson-White syndrome (WPW; 27%), and right ventricular outflow tract obstruction (25%). Cluster analysis showed that patients can be classified into 2 distinct subgroups with defined phenotypes that determine disease severity and survival. Patients in cluster 1 represented a particularly homogeneous subgroup with a milder spectrum of disease, including only patients with WPW and/or supraventricular tachycardia (SVT). Cluster 2 included patients with more diverse cardiovascular comorbidities.

Conclusions: This study represents one of the largest phenotypic characterizations of EA patients reported. The data show that EA is a heterogeneous disease, very frequently associated with cardiovascular and noncardiovascular comorbidities. Patients with WPW and SVT represent a homogeneous subgroup that presents with a less severe spectrum of disease and better survival when adequately managed. This should be considered when searching for genetic causes of EA and in the clinical setting.

Keywords: Congenital Heart Defect; Ebstein Anomaly; Epidemiology; Genetics; Phenotype.

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Conflict of interest statement

The authors declare no potential conflicts of interest.

Figures

Figure 1
Figure 1
Patient classification using cluster analysis. (A) Dendrogram illustrating the 2 main clusters obtained through hierarchical cluster analysis. WPW/SVT patients were mostly assigned to CL 1, whereas RVOTO patients were mostly assigned to CL 2. (B) Distribution of comorbidities in CL 1. (C) Distribution of comorbidities in CL 2. (D) Severity of disease per Carpentier classification in CL 1. (E) Severity of disease per Carpentier classification in CL 2. Abbreviations: ASD, atrial septal defect; CL, cluster; CRBBB, complete right bundle branch block; RVOTO, right ventricular outflow tract obstruction; SVT, supraventricular tachycardia; WPW, Wolff‐Parkinson‐White syndrome
Figure 2
Figure 2
Survival to adulthood. All patients were evaluated for survival to adulthood (age 18 years) using Kaplan–Meier analysis. The thick line represents the survival to adulthood of patients with WPW and/or SVT, who had a significantly better survival than the patients without WPW and/or SVT, represented by the dotted line. Cumulative survival for all patients is shown in the intermediate line labeled “All patients.” Abbreviations: CUM, cumulative; SVT, supraventricular tachycardia; WPW, Wolff‐Parkinson‐White syndrome
See this image and copyright information in PMC

References

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