Importance of genotype for risk stratification in arrhythmogenic right ventricular cardiomyopathy using the 2019 ARVC risk calculator

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetic disease (1:5,000 population) associated with high risk of dangerous arrhythmias and sudden cardiac death in the young. Intense exercise can facilitate the development of the disease and has been associated with arrhythmias. Globally 1 in 4 patients with this condition can develop a dangerous arrhythmia in a 10-year period.

Patients with this condition that are considered to be prone to develop dangerous arrhythmias are offered an implantable defibrillator (ICD) capable of treating arrhythmias or delivering a life-saving shock in an acute emergency. This device (the ICD) is very effective to treat arrhythmias but requires a surgical procedure and can be associated with some complications like infections, pain, unnecessary shocks and psychological impact, etc.


How do we know who is at high risk of a dangerous arrhythmia?

In the evaluation of a patient with ARVC the symptoms are very important. In particular the presence of loss of consciousness (syncope) and rapid palpitations are key.  There are different tests like making an ECG, exercise test, ambulatory ECG recording, echocardiography, cardiac magnetic resonance, etc. that helps the cardiologist to assess the risk of dangerous arrhythmias. Formulas or calculators, called “arrhythmia risk scores”, are available that can estimate the likelihood of developing an arrhythmia in the future.


What does this study add to the knowledge of the disease?

This international multicentric study which included clinical information from 554 patients with ARVC assessed the performance of the most used “ARVC risk score”, taking into consideration the genetic information. The formula predicted the occurrence of dangerous arrhythmias or sudden death better in the group of patients with ARVC caused by disease causing variants in plakophilin-2 (PKP-2) but it performed less well when considering disease causing variants in other genes like desmoplakin (DSP) or in those patients in whom a causative genetic variant could not be identified. In these patients it overestimated the risk of dangerous arrhythmias.

The authors led by Dr. Alexandros Protonotarios from the St. Bartholomew´s Hospital in London, concluded that genetic information is of outmost importance in the process of risk estimation with the “ARVC risk score” formula, and should be taken into account for the indication of preventive therapies.


Link to original article

Translated by Juan Gimeno, Virgen de la Arrixaca University Hospital, Murcia, Spain

Protonotarios A, Bariani R, Cappelletto C, Pavlou M, García-García A, Cipriani A, Protonotarios I, Rivas A, Wittenberg R, Graziosi M, Xylouri Z, Larrañaga-Moreira JM, de Luca A, Celeghin R, Pilichou K, Bakalakos A, Lopes LR, Savvatis K, Stolfo D, Dal Ferro M, Merlo M, Basso C, Freire JL, Rodriguez-Palomares JF, Kubo T, Ripoll-Vera T, Barriales-Villa R, Antoniades L, Mogensen J, Garcia-Pavia P, Wahbi K, Biagini E, Anastasakis A, Tsatsopoulou A, Zorio E, Gimeno JR, Garcia-Pinilla JM, Syrris P, Sinagra G, Bauce B, Elliott PM. Importance of genotype for risk stratification in arrhythmogenic right ventricular cardiomyopathy using the 2019 ARVC risk calculator. Eur Heart J. 2022 Aug 21;43(32):3053-3067. doi: 10.1093/eurheartj/ehac235. Erratum in: Eur Heart J. 2022 Aug 05;: PMID: 35766183; PMCID: PMC9392652.