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Eur J Heart Fail. 2019 Jun;21(6):792-800. doi: 10.1002/ejhf.1423. Epub 2019 Feb 21.

High risk of heart failure associated with desmoglein-2 mutations compared to plakophilin-2 mutations in arrhythmogenic right ventricular cardiomyopathy/dysplasia.

Author information

1
Centre de Référence Pour les Maladies Cardiaques Héréditaires, APHP, Hôpital de la Pitié Salpêtrière, Paris, France.
2
Sorbonne Universités, UPMC Université Paris 6, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, ICAN, Département de Cardiologie, Paris, France.
3
Service de Rythmologie, Centre Hospitalo-Universitaire, Amiens, France.
4
Département de Cardiologie, Hôpital Pontchaillou, Rennes, France.
5
Institut du Thorax, Centre Hospitalo-Universitaire, Nantes, France.
6
Département de Cardiologie, Centre Hospitalo-Universitaire, Marseille, France.
7
Département de Cardiologie, Centre Hospitalo-Universitaire, Lyon, France.
8
Département de Cardiologie, Centre Hospitalo-Universitaire, Lille, France.
9
AP-HP, Groupe Hospitalier Ambroise Paré, UVSQ, INSERM U1018, CESP, Boulogne, France.
10
Service de Cardiologie, Hôpital de L'Ile, Berne, Switzerland.
11
Département de Cardiologie, Centre Hospitalo-Universitaire, Tours, France.
12
Département de Cardiologie, Centre Hospitalo-Universitaire, Caen, France.
13
Département de Cardiologie, Centre Hospitalo-Universitaire Bichat-Claude-Bernard, Paris, France.
14
Emergency Department, University Hospital Zurich, Zurich, Switzerland.
15
Statistic Unit - StatEthic, Levallois-Perret, France.

Abstract

BACKGROUND:

Previous studies suggested that genetic status affects the clinical course of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients. The aim of this study was to compare the outcome of desmoglein-2 (DSG2) mutation carriers to those who carry the plakophilin-2 (PKP2) mutation, the most common ARVC/D-associated gene.

METHODS AND RESULTS:

Consecutive ARVC/D patients carrying a pathogenic mutation in PKP2 or DSG2 were selected from a national ARVC/D registry. The cumulative freedom from sustained ventricular arrhythmia and cardiac transplantation/death from heart failure (HF) during follow-up was assessed, compared between PKP2 and DSG2, and predictors for ventricular arrhythmia and HF events determined. Overall, 118 patients from 78 families were included: 27 (23%) carried a DSG2 mutation and 91 (77%) a PKP2 mutation. There were no significant differences between DSG2 and PKP2 mutation carriers concerning gender, proband status, age at diagnosis, T-wave inversion, or right ventricular dysfunction at baseline. DSG2 patients displayed more frequent epsilon wave (37% vs. 17%, P = 0.048) and left ventricular dysfunction at diagnosis (54% vs. 10%, P < 0.001). During a median follow-up of 5.6 years (2.5-16), DSG2 and PKP2 mutation carriers displayed a similar risk of sustained ventricular arrhythmia (log-rank P = 0.20), but DSG2 mutation carriers were at higher risk of transplantation/HF-related death (log-rank P < 0.001). The presence of a DSG2 mutation vs. PKP2 mutation was a predictor of transplantation/HF-related death in univariate Cox analysis (P = 0.0005).

CONCLUSIONS:

In this multicentre cohort, DSG2 mutation carriers were found to be at high risk of end-stage HF compared to PKP2 mutation carriers, supporting careful haemodynamic monitoring of these patients. The benefit of early HF treatment needs to be assessed in DSG2 carriers.

KEYWORDS:

Arrhythmogenic right ventricular cardiomyopathy/dysplasia; Cardiac transplantation; Desmoglein-2; Heart failure; Plakophilin-2; Ventricular arrhythmia

PMID:
30790397
DOI:
10.1002/ejhf.1423

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