Published online before print February 10, 2009, doi: 10.1161/CIRCEP.108.782888
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Original Articles |
Yield of Genetic Screening in Inherited Cardiac Channelopathies
How to Prioritize Access to Genetic Testing
From the Molecular Cardiology (R. Bai, C.N., R. Bloise, N.M., S.G.P.), IRCCS Fondazione Salvatore Maugeri, Pavia, Italy; Department of Cardiology (S.G.P.), University of Pavia, Pavia, Italy; Cardiovascular Genetics Program (S.G.P.), Leon Charney Division of Cardiology, New York University, New York, NY; and Department of Cardiology/Internal Medicine (R. Bai), Tong-Ji Hospital, Tong-Ji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China.
Correspondence to Silvia G. Priori, MD, PhD, Molecular Cardiology, Salvatore Maugeri Foundation, University of Pavia, Via Ferrata 8; 27100 Pavia, Italy. E-mail spriori{at}fsm.it
Received March 27, 2008; accepted November 6, 2008.
Background— Identification of mutations in cardiac ion channel genes concurs to the diagnosis of long-QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. However, because 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 long-QT syndrome-genes screening, those with clinical diagnosis of long-QT syndrome 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 Brugada syndrome ECG pattern (51 of 405; 13%) corresponding to a cost of US $21441 per positive genotyping. In conclusive Brugada syndrome patients the presence of atrioventricular block (odds ratio: 3.3, CI: 1.8 to 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 1 positive genotyping).
Conclusions— Genotyping can be performed at reasonable cost in individuals with conclusive diagnosis of long-QT syndrome and catecholaminergic polymorphic ventricular tachycardia, and in patients with type I Brugada syndrome ECG with atrioventricular block. These patients should be given priority to access genetic testing.
Key Words: genetics • long-QT syndrome • catecholaminergic VT • Brugada syndrome
CLINICAL PERSPECTIVE
Related Articles
- Cost-Effectiveness of Genotyping in Inherited Arrhythmia Syndromes: Are We Getting Value for the Money?
- Arthur A.M. Wilde and Yigal M. Pinto
Circ Arrhythm Electrophysiol 2009 2: 1-3.[Extract] [Full Text] [PDF]
- Yield of Genetic Screening in Inherited Cardiac Channelopathies: How to Prioritize Access to Genetic Testing
- Rong Bai, Carlo Napolitano, Raffaella Bloise, Nicola Monteforte, and Silvia G. Priori
Circ Arrhythm Electrophysiol 2009 2: 6-15.[Abstract] [Full Text] [PDF]
This article has been cited by other articles:
 |
|
 |
|
  M. Cerrone and S. G. Priori Routine electrocardiogram and medical history in syncope: a simple approach can identify most high-risk patients Europace, August 25, 2009; (2009) eup230v1. [Full Text] [PDF]
|
|
|
|
 |
|
 A. A.M. Wilde and Y. M. Pinto Cost-Effectiveness of Genotyping in Inherited Arrhythmia Syndromes: Are We Getting Value for the Money? Circ Arrhythm Electrophysiol, February 1, 2009; 2(1): 1 - 3. [Full Text] [PDF]
|
|