Community detection of long QT syndrome with a clinical registry: An alternative to ECG screening programs?
Introduction
Sudden unexpected death has a devastating effect on families and communities, particularly when it occurs in the young. Yet if presymptomatic individuals with an inherited risk can be identified in the community, lifesaving interventions can be provided.1 One cause of sudden death in the young with a prevalence estimated at 4 of 10,000 is long QT syndrome (LQTS), characterized by prolonged ventricular repolarization and susceptibility to life-threatening arrhythmias.2
For LQTS and other causes of sudden cardiac death (SCD) in the young, much discussion surrounds the value of electrocardiogram (ECG) screening of the general pediatric population or specific populations considered to be at a higher risk.3, 4, 5, 6, 7 The ECG, however, is neither sensitive nor specific, both of which are essential requirements of any clinical screening program.8 Consequently, children are referred for further assessment that may be unwarranted, increasing the financial costs and anxiety associated with uncertain diagnoses.9
An alternative approach is to identify probands and then exhaustively screen family members. With an autosomal dominant disease such as LQTS, half the targeted population would be affected individuals and so the overdiagnosis from poor test specificity is reduced, particularly when supported by genetic testing.
A consent-based clinical registry for patients with LQTS has been in operation in the northern region of New Zealand since 2003 (with ethics committee approval). Since the establishment of the registry, there have been efforts to raise awareness of LQTS among clinicians and the public. The LQTS registry is part of a wider inherited heart disease registry run by the Cardiac Inherited Diseases Group (CIDG), a network of clinicians and scientists. This report addresses the question as to whether this LQTS registry (and thus others like it) can identify LQTS in the community at a high enough frequency that it might be a viable alternative to community ECG-based screening programs.
Section snippets
Methods
New Zealand has a population of 4.43 million and a relatively large geographical area with a density of 16 people per square kilometer.10 The northern region (defined in this report as the 5 northernmost district health board areas Northland, Auckland, Waitemata, Counties Manukau, and Waikato), in which the CIDG and the LQTS registry are based, comprises nearly half of New Zealand’s population (2.03 million) and includes the cities of Auckland and Hamilton.
Since 2003, living probands suspected
Results
Eighty-five probands with definite LQTS and 27 probands with probable LQTS were enrolled in the registry (Figure 1). The reasons for referral were as follows: 7 (6%) sudden unexplained deaths, 7 (6%) sudden unexplained deaths of family members, 82 (73%) cardiac events, and 16 (14%) incidental ECG abnormalities. A further 163 definite and 34 probable cases were identified through family screening, giving a total of 309 cases of LQTS in the northern region of New Zealand. Baseline characteristics
Discussion
We have demonstrated that a clinical LQTS registry incorporating diagnostic genetic testing can facilitate identification of many patients with LQTS, including victims of sudden unexplained death and their families. Community-based ECG screening elsewhere has led to an estimated prevalence of LQTS of 4 of 10,000.2 The registry and program we describe, which has been in existence for 9 years, has thus far detected 1.5 of 10,000 individuals with LQTS in the northern region of New Zealand and 2.2
Conclusions
A high level of community detection of LQTS is possible by using a clinical registry with an active program to detect probands and screen their families. In some areas, this has detected more than half of the anticipated prevalence, despite the limited resources of the registry and only partially successful family screening. This detection frequency can be expected to increase in time as further family cascade screening takes place, particularly if resources are increased to facilitate this
Acknowledgments
This article is presented on behalf of the Cardiac Inherited Diseases Group, which is generously supported by Cure Kids. Nikki Earle is supported by a postgraduate scholarship from the Auckland Medical Research Foundation.
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