TY - JOUR
T1 - Nationwide experience of catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations
AU - Broendberg, Anders Krogh
AU - Nielsen, Jens Cosedis
AU - Bjerre, Jesper
AU - Pedersen, Lisbeth Noerum
AU - Kristensen, Jens
AU - Henriksen, Finn Lund
AU - Bundgaard, Henning
AU - Jensen, Henrik Kjaerulf
N1 - © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Objective The aim of this study was to characterise disease penetrance, course of disease and use of antiarrhythmic medication and implantable cardioverter-defibrillator (ICD) therapy in a Danish nationwide cohort of patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) due to mutations in the ryanodine receptor-2 (RyR2) gene. Methods The study population was identified through the national hereditary heart disease database (Progeny). The study population was divided into three groups: probands, symptomatic and asymptomatic relatives. Results We identified 23 symptomatic probands, 18 symptomatic and 10 asymptomatic relatives with a RyR2 mutation. Twenty (87%) probands and 10 (36%) relatives had severe presenting symptoms (sudden cardiac death (SCD), aborted SCD (ASCD) or syncope). As compared with symptomatic relatives, probands had lower age at onset of symptoms (16 years (IQR, 10-33) vs 43 years (IQR, 25-54), p<0.0001) and were more prone to fatal or near-fatal events (ASCD, SCD) (16vs5, p<0.0001). Twenty-eight patients had an ICD implanted, and eight experienced appropriate ICD therapy during follow-up (65 months (IQR, 43-175)). Electrical storm was seen in two of the 28 ICD treated patients (7%). No patients receiving treatment died during follow-up (57 months (IQR, 32-139)). Multifocal atrial tachycardia was the predominant symptom in five patients. Conclusions In a national cohort of RyR2 mutation-positive CPVT patients, SCD, ASCD and syncope were presenting events in the majority of probands and also occurred in 36% of relatives identified through family screening. Probands were younger at disease onset and more prone to fatal or near-fatal events than relatives.
AB - Objective The aim of this study was to characterise disease penetrance, course of disease and use of antiarrhythmic medication and implantable cardioverter-defibrillator (ICD) therapy in a Danish nationwide cohort of patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) due to mutations in the ryanodine receptor-2 (RyR2) gene. Methods The study population was identified through the national hereditary heart disease database (Progeny). The study population was divided into three groups: probands, symptomatic and asymptomatic relatives. Results We identified 23 symptomatic probands, 18 symptomatic and 10 asymptomatic relatives with a RyR2 mutation. Twenty (87%) probands and 10 (36%) relatives had severe presenting symptoms (sudden cardiac death (SCD), aborted SCD (ASCD) or syncope). As compared with symptomatic relatives, probands had lower age at onset of symptoms (16 years (IQR, 10-33) vs 43 years (IQR, 25-54), p<0.0001) and were more prone to fatal or near-fatal events (ASCD, SCD) (16vs5, p<0.0001). Twenty-eight patients had an ICD implanted, and eight experienced appropriate ICD therapy during follow-up (65 months (IQR, 43-175)). Electrical storm was seen in two of the 28 ICD treated patients (7%). No patients receiving treatment died during follow-up (57 months (IQR, 32-139)). Multifocal atrial tachycardia was the predominant symptom in five patients. Conclusions In a national cohort of RyR2 mutation-positive CPVT patients, SCD, ASCD and syncope were presenting events in the majority of probands and also occurred in 36% of relatives identified through family screening. Probands were younger at disease onset and more prone to fatal or near-fatal events than relatives.
KW - Adolescent
KW - Adult
KW - Child
KW - DNA/genetics
KW - DNA Mutational Analysis
KW - Electrocardiography
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Mutation
KW - Pedigree
KW - Retrospective Studies
KW - Ryanodine Receptor Calcium Release Channel/genetics
KW - Tachycardia, Ventricular/genetics
KW - Young Adult
U2 - 10.1136/heartjnl-2016-310509
DO - 10.1136/heartjnl-2016-310509
M3 - Journal article
C2 - 28237968
SN - 1355-6037
VL - 103
SP - 901
EP - 909
JO - Heart
JF - Heart
IS - 12
ER -