Family tree helps estimate mortality risk for inherited arrhythmia patients

Family tree helps estimate mortality risk for inherited arrhythmia patients 29 February 2012 MedWire News: Dutch researchers have reconstructed family trees to estimate the mortality risk for individuals with inherited arrhythmia syndromes. “Our data might help to further guide treatment and screening strategies in an increasing group of (asymptomatic) mutation carriers who are detected by molecular genetic testing in families with an inherited arrhythmia syndrome,” report Eline Nannenberg (Academic Medical Center, Amsterdam) and co-authors. Although the risk for sudden cardiac death in symptomatic identified mutation carriers who are untreated is substantial, in asymptomatic carriers the risk is ill-defined, they explain. Preventive lifestyle advice and pharmacologic or invasive treatment can be offered, but these have side effects and impact quality of life. Nannenberg and team further investigated treatment options and screening strategies in asymptomatic patients using the Family Tree Mortality Ratio (FTMR) Method to ascertain mortality risk in six major autosomal syndromes caused by specific mutations. These were: long QT syndromes types 1, 2, and 3 (LQTS1, 2, 3); Brugada syndrome; SCN5A overlap syndrome (LQTS3/Brugada syndrome/conduction disease); and RYR2-gene related Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). The researchers used Dutch archives to reconstruct family trees for patients with these syndromes and compared death statistics in 266 people who carried a mutation in a gene linked with arrhythmia, 904 family members with a 50% likelihood for having the mutation, and the general Dutch population. They were then able to identify age ranges during which the risk for mortality increased for mutation carriers and their family members, but they had not yet been diagnosed or treated for the condition. The findings are published in Circulation: Cardiovascular Genetics. They reveal that mortality risk in LQTS1 was significantly increased during childhood, at the ages of 1–19 years, at a standardized mortality ratio (SMR) of 3.0. Additional analysis identified a smaller specific age category in which the excess mortality was significant: between 1 and 9 years, at an SMR of 2.9. In LQTS1, the SMR increased starting from the age of 15 years, at an SMR of 2.6 from 15 to 19 years, but only reached significance between 30 and 39 years, at an SMR of 4.0. There was also severe excess mortality between the ages of 15 and 19 years, at an SMR of 5.8, in LQTS3 mutation carriers. Severe excess mortality in SCN5a increased between the ages of 10 and 14 years, at an SMR of 9.8 and between 20 and 39 years, at an SMR of 3.8. However, after the age of 60 years, no excess mortality was observed. Mortality risk in catecholaminergic polymorphic ventricular tachycardia (CPVT) was highest between the ages of 20 and 39 years, at an SMR of 3.0, and in Brugada syndrome, was highest between the ages of 40 and 59 years, at an SMR of 1.72. “We have to be careful not to draw conclusions for families with arrhythmias caused by different mutations,” said Nannenberg in a press statement. “However, this new data can guide screening. In LQTS1, we advise starting genetic and heart screening of first-degree family members (children, siblings, parents) at a very young age,” he recommended. MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012 Circ Cardiovasc Genet 2012; Advance online publication