In order to bring you the best possible user experience, this site uses Javascript. If you are seeing this message, it is likely that the Javascript option in your browser is disabled. For optimal viewing of this site, please ensure that Javascript is enabled for your browser.


The free consultation period for this content is over.

It is now only available year-round to ESC Professional Members, Fellows of the ESC, and Young combined Members

Genetic variant score predicts cardiac events in arrhythmogenic right ventricular cardiomyopathy

Session Poster Session 1

Speaker Anneli Svensson

Congress : ESC Congress 2018

  • Topic : valvular, myocardial, pericardial, pulmonary, congenital heart disease
  • Sub-topic : Myocardial Disease - Clinical: Arrhythmogenic Right Ventricular Cardiomyopathy
  • Session type : Poster Session
  • FP Number : P688

Authors : A Svensson (Linkoping,SE), KH Haugaa (Oslo,NO), W Zareba (Rochester,US), HK Jensen (Aarhus,DK), H Bundgaard (Copenhagen,DK), T Gilljam (Gothenburg,SE), T Madsen (Aalborg,DK), J Hansen (Hellerup,DK), L Karlsson (Linkoping,SE), A Green (Linkoping,SE), B Polonsky (Rochester,US), T Edvardsen (Oslo,NO), JH Svendsen (Copenhagen,DK), C Gunnarsson (Linkoping,SE), PG Platonov (Lund,SE)

15 views

Authors:
A. Svensson1 , K.H. Haugaa2 , W. Zareba3 , H.K. Jensen4 , H. Bundgaard5 , T. Gilljam6 , T. Madsen7 , J. Hansen8 , L. Karlsson1 , A. Green9 , B. Polonsky3 , T. Edvardsen2 , J.H. Svendsen10 , C. Gunnarsson11 , P.G. Platonov12 , 1Department of Cardiology and Department of Medical and Health Sciences, Linkoping University - Linkoping - Sweden , 2Department of Cardiology, Centre for Cardiological Innovation, Institute for Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway and University of Oslo - Oslo - Norway , 3University of Rochester Medical Center, Rochester, NY - Rochester - United States of America , 4Department of Cardiology, Aarhus University Hospital, and Department of Clinical Medicine, Aarhus University - Aarhus - Denmark , 5Unit for Inherited Cardiac Diseases, the Heart Center, National University Hospital, Rigshospitalet - Copenhagen - Denmark , 6Department of Cardiology, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg - Gothenburg - Sweden , 7Department of Cardiology, Aalborg University Hospital - Aalborg - Denmark , 8Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen - Hellerup - Denmark , 9Department of Clinical Genetics, Department of Clinical Experimental Medicine, Linköping University - Linkoping - Sweden , 10Department of Cardiology, the Heart Centre, Rigshospitalet, University of Copenhagen, Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen - Copenhagen - Denmark , 11Department of Clinical Genetics, Department of Clinical Experimental Medicine, Linköping University, Centre for Rare Diseases in South East Region of Sweden, Linköping University - Linkoping - Sweden , 12Department of Cardiology, Clinical Sciences, Lund University, and Arrhythmia Clinic, Skåne University Hospital - Lund - Sweden ,

Citation:
European Heart Journal ( 2018 ) 39 ( Supplement ), 102

Background: Whether genetic information may contribute to risk stratification of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains uncertain. The Combined Annotation Dependent Depletion (CADD) score, a bioinformatic tool that measures the pathogenicity of genetic variants, has not been tested for its association with clinical manifestations of ARVC.

Objective: We aimed to assess whether CADD score is associated with cardiac events in individuals carrying pathogenic variants of plakophilin-2 (PKP-2) gene.

Methods: In this retrospective study, all individuals enrolled in the Nordic ARVC Registry and the North American Multidisciplinary ARVC Study carrying PKP-2 variants that according to the American College of Medical Genetics and Genomics (ACMG) were classified as pathogenic or likely pathogenic were included. In total, 36 unique genetic variants were reported in 187 patients (93 males, 75 probands, 101 with definite ARVC diagnosis by Task Force 2010 and median age of 38 [IQR 24–52] years). No individuals had a pathogenic genetic variant in any other ARVC-related gene. CADD scores were calculated and their association with age at (1) first ventricular tachycardia/ventricular fibrillation (VT/VF) defined as ventricular tachycardia, appropriate ICD therapy or aborted cardiac arrest or (2) cardiac event (VT/VF or syncope) evaluated. Kaplan–Meier analysis and Cox regression analysis adjusted for gender were used to assess relationship between CADD score and the risk of cardiac events before the age of 60 years.

Results: Cardiac events were reported in 81 patients (43%) and VT/VF in 63 (34%). CADD score was higher in patients with cardiac events than in those without (30.9 vs. 28.7, p=0.023) and Kaplan-Meier analysis indicated higher frequency of cardiac events in those with CADD score >30 (log rank p=0.011, Figure). In the Cox regression analysis, CADD >30 (upper tertile) was significantly associated with the risk of cardiac events (HR=1.80, 95% CI 1.12–2.88, p=0.014). No association between cardiac event rates and the most common genetic variant types (splice site, deletion, nonsense) was observed.

Conclusions: We are the first to report a significant correlation between PKP-2 mutation characteristics assessed using CADD-score and the age at first clinical manifestations of ARVC, thus indicating the potential of genetic information for risk stratification.

CADD score and risk of cardiac events


Based on your interests

Three reasons why you should become a member

Become a member now
  • 1Access your congress resources all year-round on the New ESC 365
  • 2Get a discount on your next congress registration
  • 3Continue your professional development with free access to educational tools
Become a member now

Our sponsors

ESC 365 is supported by Bayer, Boehringer Ingelheim, Bristol-Myers Squibb and Pfizer Alliance, and Novartis Pharma AG. The sponsors were not involved in the development of this platform and had no influence on its content.

logo esc

Our mission: To reduce the burden of cardiovascular disease

Who we are