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High risk of heart failure associated with desmoglein-2 mutations compared to plakophilin-2 mutations in arrhythmogenic right ventricular cardiomyopathy/dysplasia
- Source :
- European Journal of Heart Failure, European Journal of Heart Failure, Oxford University Press (OUP), 2019, ⟨10.1002/ejhf.1423⟩, European Journal of Heart Failure, 2019, ⟨10.1002/ejhf.1423⟩
- Publication Year :
- 2018
-
Abstract
- International audience; 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.
- Subjects :
- Proband
Adult
Male
medicine.medical_specialty
Heterozygote
[SDV]Life Sciences [q-bio]
DNA Mutational Analysis
Desmoglein-2
030204 cardiovascular system & hematology
Right ventricular cardiomyopathy
03 medical and health sciences
Electrocardiography
Young Adult
0302 clinical medicine
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Internal medicine
medicine
Humans
Arrhythmogenic Right Ventricular Dysplasia
Retrospective Studies
Heart Failure
Plakophilin-2
Desmoglein 2
business.industry
DNA
Middle Aged
medicine.disease
Arrhythmogenic right ventricular cardiomyopathy/dysplasia
3. Good health
Pedigree
Transplantation
Phenotype
Dysplasia
Heart failure
Cohort
Mutation (genetic algorithm)
Mutation
Cardiology
Ventricular arrhythmia
Cardiac transplantation
Female
Cardiology and Cardiovascular Medicine
business
Plakophilins
Follow-Up Studies
Subjects
Details
- ISSN :
- 18790844 and 13889842
- Volume :
- 21
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- European journal of heart failure
- Accession number :
- edsair.doi.dedup.....84deb3c560c4e4169c835ed35be6a188