Viewpoint: CounterpointRoutine ECG screening in infancy and early childhood should not be performed
Section snippets
Evaluation of outcome of neonatal ECG screening
Population-based ECG screening programs have established the likely prevalence of LQTS in Italian and Japanese children at around 1 in 2000.9, 10, 11 However, as Saul et al admit, no studies of clinical utility of such a program have been carried out. We do not know whether such a program will save lives or not, nor what the adverse consequences will be. These facts alone indicate that further research is required before mandatory mass ECG screening should be allowed to become health policy.
The ECG is an unreliable diagnostic tool with unacceptable reproducibility, specificity, and sensitivity
Saul et al propose to reevaluate every infant found with a corrected QT (QTc) interval of greater than 0.45 seconds at 3–4 weeks of life. Given that an average QTc interval for gene carriers with LQTS is 0.454 seconds,27 almost half of the individuals may not be detected. Clearly, at least one-third of the long QT gene carriers will be missed by this cutoff. One can only guess what the future medicolegal consequences of missing so many gene carriers will be, particularly in the United States.
Unintended costs and adverse effects of population screening
There have been no studies to evaluate unintended costs or potential adverse effects of population ECG screening, including of athletes.33 These costs may, for example, be financial, related to repeated investigations of the individual and family, employment issues, and unnecessary treatments, or psychosocial, from being given a wrong or uncertain diagnosis.
Mass screening and mass uncertainty
Saul et al admit that there may be unknown “minor adverse effects of population-based ECG screening.” One outcome is uncertainty for a
Excluding LQTS in borderline cases: The questionable application of genetic testing
An essential feature of any screening program is the ability to finally diagnose or exclude the condition in 100% of cases identified. Newborn oximetry is the most recent example, where an echocardiogram diagnoses or excludes congenital heart disease.35
It is very hard to “undo” a wrong diagnosis of LQTS.36 Saul et al suggest genetic testing as a means to reclassify false-positive patients, that is, lack of a known mutation implying that LQTS is not present. Given that at least 20%–30% of those
Paucity of data for non-Whites
Ethnic diversity is reflected in the ECG and in the genes. ECGs in Italian infants and in Japanese children may be different from those in other ethic groups. Different races have different repolarization patterns.39, 40 We do not know whether, on a population basis, infants from different races will have longer or shorter QT intervals.
With regard to genetics, it is increasingly evident that a pathogenicity of genetic variants varies with ancestry. For example, R1193Q in SCN5A causes Brugada
The better alternative: Detection of inherited heart diseases in the community through an active multidisciplinary program to detect probands and screen family members, based around a clinical registry
The many inherited heart conditions that are known to cause sudden death in young people are being detected in thousands internationally as multidisciplinary cardiac genetic services develop around the world.8, 46, 47, 48, 49, 50, 51
In parts of New Zealand, 1 in 4500 of the community at large have already been identified with LQTS.4 This particular service is poorly funded, with only one part-time coordinator in a country of 4.3 million over a geographic area the size of the United Kingdom.
Conclusion
There remain far too many unknowns around neonatal ECG screening for LQTS, and it fails to meet the accepted criteria for population screening for disorders.61 Mandatory screening has the potential to cause significant harm and to waste public health resources, and it requires much more research before implementation should be considered.
Instead, we recommend that health funding agencies devote efforts toward cardiac genetic services in general. They should raise public and medical awareness of
References (61)
- et al.
Community detection of long QT syndrome with a clinical registry: an alternative to ECG screening programs?
Heart Rhythm
(2013) - et al.
Active cascade screening in primary inherited arrhythmia syndromes: does it lead to prophylactic treatment?
J Am Coll Cardiol
(2010) - et al.
Clinical implications for patients with long QT syndrome who experience a cardiac event during infancy
J Am Coll Cardiol
(2009) - et al.
Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals
J Am Coll Cardiol
(2011) - et al.
Risk factors for recurrent syncope and subsequent fatal or near-fatal events in children and adolescents with long QT syndrome
J Am Coll Cardiol
(2011) - et al.
Posthumous diagnosis of long QT syndrome from neonatal screening cards
Heart Rhythm
(2010) - et al.
Inaccurate electrocardiographic interpretation of long QT: the majority of physicians cannot recognize a long QT when they see one
Heart Rhythm
(2005) - et al.
Pulse oximetry with clinical assessment to screen for congenital heart disease in neonates in China: a prospective study
Lancet
(2014) - et al.
Spectrum and prevalence of cardiac sodium channel variants among black, white, Asian, and Hispanic individuals: implications for arrhythmogenic susceptibility and Brugada/long QT syndrome genetic testing
Heart Rhythm
(2004) - et al.
Redefining the ECG in urban South Africans: electrocardiographic findings in heart disease-free Africans
Int J Cardiol
(2013)
Nav1.5/R1193Q polymorphism is associated with both long QT and Brugada syndromes
Can J Cardiol
Guidelines for genetic testing of inherited cardiac disorders
Heart Lung Circ
The emerging role of the cardiac genetic counselor
Heart Rhythm
Familial cardiological and targeted genetic evaluation: low yield in sudden unexplained death and high yield in unexplained cardiac arrest syndromes
Heart Rhythm
Prospective, population-based long QT molecular autopsy study of postmortem negative sudden death in 1 to 40 year olds
Heart Rhythm
Review of first 5 years of screening for familial hypercholesterolaemia in the Netherlands
Lancet
Origin of the Swedish long QT syndrome Y111C/KCNQ1 founder mutation
Heart Rhythm
Diagnostic yield in sudden unexplained death and aborted cardiac arrest in the young: the experience of a tertiary referral center in the Netherlands
Heart Rhythm
Cardiac channel molecular autopsy: insights from 173 consecutive cases of autopsy-negative sudden unexplained death referred for postmortem genetic testing
Mayo Clin Proc
Con: Newborn screening to prevent sudden cardiac death?
Heart Rhythm
Rational and objectives for ECG screening in infancy and early childhood
Heart Rhythm
Risk stratification in the long-QT syndrome
N Engl J Med
Electrocardiogram screening of infants for long QT syndrome: survey of pediatric cardiologists in North America
J Electrocardiol
Cascade screening in families with inherited cardiac diseases driven by cardiologists: feasibility and nationwide outcome in long QT syndrome
Cardiology
Founder mutations characterise the mutation panorama in 200 Swedish index cases referred for long QT syndrome genetic testing
BMC Cardiovasc Disord
Yield of molecular and clinical testing for arrhythmia syndromes: report of 15 years’ experience
Circulation
Prevalence of the congenital long-QT syndrome
Circulation
Long QT syndrome and associated gene mutation carriers in Japanese children: results from ECG screening examinations
Clin Sci (Lond)
Electrocardiographic screening of 1-month-old infants for identifying prolonged QT intervals
Circ Arrhythm Electrophysiol
Arrhythmia phenotype during fetal life suggests long-QT syndrome genotype: risk stratification of perinatal long-QT syndrome
Circ Arrhythm Electrophysiol
Cited by (22)
Important unanswered research questions related to torsades de pointes
2022, Torsades de PointesThe natural history of fetal long QT syndrome
2016, Journal of ElectrocardiologyCitation Excerpt :Fifth, anticipatory postnatal care from a prenatal diagnosis improves outcome has been shown to improve outcome [25]. Lastly, screening every newborn with a 12 lead ECG is controversial, and will not detect all cases of LQTS [26]. Once suspected, the diagnosis of fetal LQTS can be confirmed by fMCG in two ways.
Genetic purgatory and the cardiac channelopathies: Exposing the variants of uncertain/unknown significance issue
2015, Heart RhythmCitation Excerpt :Then, amidst the calls for universal infant ECG screening for the early detection of LQTS,34 calls for universal genetic screening of the LQTS genes have surfaced. Although the former is clearly debatable,35 the latter has failed totally to respect the issue of background genetic noise. If 1 in 2000 whites have LQTS, and we accept the high-end contribution of 10% for SCN5A-mediated LQTS (LQT3), then accordingly, this implies that approximately 1 in 20,000 whites have LQT3.
Letter to the editor - Detection of long QT syndrome in the community
2015, Heart RhythmNeonatal ECG screening: Opinions and facts
2015, Heart RhythmComparison of formulas for calculation of the corrected QT interval in infants and young children
2015, Journal of Pediatrics
Dr Skinner receives salary support from Cure Kids.