Mortality of Inherited Arrhythmia Syndromes; Insight into Their Natural History
Background—For most arrhythmia syndromes the risk of sudden cardiac death (SCD) for asymptomatic mutation carriers is ill-defined. Data on the natural history of these diseases are therefore essential. The Family Tree Mortality Ratio (FTMR) method offers the unique possibility to study the natural history at a time when the disease was not known and patients received no treatment.
Methods and Results—In six inherited arrhythmia syndromes, caused by specific mutations, we analyzed all-cause mortality with the FTMR method (main outcome measure: Standardized Mortality Ratio (SMR)). In long QT syndrome type 1 (LQTS1), severely increased mortality risk during all years of childhood was observed (1-19 years), in particular during the first 10 years of life (SMR 2.9, 95% CI 1.5-5.1). In LQTS2, we observed increasing SMRs starting from the age of 15 which just reached significance between 30-39 years (SMR 4.0, 95% CI 1.1-10.0). In LQTS3, the SMR was increased between 15 and 19 years (SMR 5.8, 95% CI 1.2-16.9). In the SCN5A-overlap syndrome excess mortality was observed between age 10 and 59, with a peak between 20-39 years (SMR 3.8, 95 % CI 2.5-5.7). In Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), excess mortality was restricted to age category 20-39 years (SMR 3.0, 95% CI 1.3-6.0). In Brugada syndrome, excess mortality was observed between 40-59 years (SMR 1.79, 95% CI 1.2-2.4), in particular in males.
Conclusions—We identified age ranges during which the mortality risk becomes manifest in an unselected and untreated population. This can guide screening of these families.
- Received September 5, 2011.
- Accepted December 29, 2011.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited