on February 10, 2009
Published online before print February 10, 2009, doi: 10.1161/CIRCEP.108.782888
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Original Article |
Yield of Genetic Screening in Inherited Cardiac Channelopathies: How to Prioritize Access to Genetic Testing
1 Maugeri Foundation, Pavia, Italy;
2 IRCCS Fondazione Salvatore Maugeri, University of Pavia
3 E-mail: spriori{at}fsm.it
Background—Identification of mutations in cardiac ion channel genes concurs to the diagnosis of long QT syndrome (LQTS), Brugada syndrome (BrS) and catecholaminergic polymorphic ventricular tachycardia (CPVT). However, since availability of genetic screening is still limited and reimbursement policies are lacking, there is a need of evidence-based criteria to prioritize access to genetic testing for these diseases.
Methods and Results—We determined the yield of genetic testing and cost per positive genotyping in 1394 consecutive probands. Among the 546 patients referred for LQTS-genes screening, those with clinical diagnosis of LQTS had the highest yield (64%) and lowest cost (US $8418) for each positive genotyping. Among 798 individuals screened for mutation on the SCN5A gene, the highest yield was obtained in patients with Type 1 BrS ECG pattern (51/405; 13%) corresponding to a cost of US $21441 per positive genotyping. In conclusive BrS patients the presence of atrioventricular block (OR: 3.3, CI1.8-6.1; P=0.0001) increases the yield (23%) of genotyping and reduces its cost (US$ 11700). Among 175 patients screened on RyR2 gene, those with documented bidirectional ventricular tachycardia had the highest incidence (62%) of mutations and the lowest cost (US $5263) per positive genotyping. Genetic screening of unselected family members of sudden cardiac death victims and idiopathic ventricular fibrillation survivors is largely ineffective (yield of 9%) and costly (US$ 71430 per one positive genotyping).
Conclusions—Genotyping can be performed at reasonable cost in individuals with conclusive diagnosis of LQTS and CPVT, and in patients with Type I BrS ECG with atrioventricular block. These patients should be given priority to access genetic testing.
Key Words: genetics • long-QT syndrome • catecholaminergic VT • Brugada Syndrome
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