Elsevier

Heart Rhythm

Volume 10, Issue 2, February 2013, Pages 233-238
Heart Rhythm

Community detection of long QT syndrome with a clinical registry: An alternative to ECG screening programs?

https://doi.org/10.1016/j.hrthm.2012.10.043Get rights and content

Background

Long QT syndrome (LQTS) prevalence is estimated at 4 of 10,000 based on community electrocardiogram (ECG) screening, about which there is disagreement regarding efficacy, accuracy, cost-effectiveness, and practicality. Family studies of autosomal dominant conditions such as LQTS have revealed 8–9gene-positive family members per proband.

Objective

To evaluate a cardiac/genetic registry and family screening program as a tool to identify LQTS in the community.

Methods

Possible LQTS probands were referred to the New Zealand Cardiac Inherited Disease service. The registry was first established in the northern region (population 2.03 million), including central Auckland (population 0.46 million). After clinical evaluation, genetic testing and family cascade screening were initiated. Genotype-positive individuals were classified as definite LQTS, and others were classified as definite or probable LQTS by clinical and ECG criteria.

Results

One hundred twelve probands were identified (presentation: 7 sudden death, 82 cardiac event, 16 ECG abnormality, and 7 sudden death of a family member). Following cascade screening, 309 patients with LQTS were identified (248 definite and 61 probable). Two hundred twenty patients had LQTS-causing mutations identified (120 [55%] LQT1, 78 [35%] LQT2, 19 [9%] LQT3, 1 [0.5%] LQT 5, and 2 [1%] LQT7). Thus far, an average of 2.1 definitely or probably affected family members have been identified per proband. The community detection rate is 1.5 of 10,000 for the whole region and 2.2 of 10,000 in Auckland.

Conclusions

A high level of community detection of LQTS is possible using a clinical registry. With adequate resourcing, this has the potential to be an effective alternative to community ECG screening.

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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