Response relating to the latest evidence summary produced by the NSC

Response relating to the latest evidence summary produced by the National Screening Committee on: Screening to reduce sudden cardiac death in people aged 12-39 years: an appraisal against UKNSC criteria

We read with interest the report commissioned by the UK National Screening Committee (NSC) that essentially summarised part of the existing literature on screening to reduce sudden cardiac death (SCD) in young individuals. Although, there is little doubt, based on current evidence, that screening of young individuals for conditions predisposing to SCD remains a challenge, the review commissioned does very little to advance the field. The false premise and misleading conclusions of the report are a cause for concern as it depicts the field of inherited cardiac diseases and sports cardiology void of any evidence to guide investigation and management of individuals suspected or diagnosed with conditions associated with SCD. Of most concern, however, is the fact that this document will be potentially read by the thousands of families devastated by SCD and will falsely lead them to believe that there is very little anyone can do to prevent further tragedies in their family. In addition, this review is likely to cause confusion and undo all the hard work that the charitable organization Cardiac Risk in the Young (CRY) has done, as its conclusions are in direct opposition to the recommendations of the Department of Health and the National Institute of Health and Care Excellence (NICE).

Although we concede that high quality evidence relating to the effectiveness of screening in preventing SCD is lacking, it is imperative that major parts of this report are revised to ensure the NSC provides the public and in particular health system stakeholders, policy and decision makers with accurate conclusions. Below we provide a list of key points that should be reviewed. It is worth noting that most of these points were highlighted to the NSC during the consultation process. Unfortunately, it appears that the views and information provided by experts in the field were not conveyed to the authors of the document and as such the literature review forming the basis of this summary missed important evidence. The involvement of individuals with expertise in the field under investigation is of paramount importance in order to reach accurate and clinically useful conclusions that will benefit the population’s health.

  1. Incidence data in Europe and the rest of the World: We disagree with the authors that there is little peer-reviewed evidence relating to the incidence of SCD in the young. There are numerous studies in multiple countries in the literature that report on the incidence of SCD in the young, many quoted by the authors of the NSC review. Although there is variability relating to the quality of the evidence and definitions of the terms “young” and “athlete”, it is the responsibility of the reviewers to assess the quality of the data. For example data relating to the studies by Maron et al. are predominantly based on a large dataset that Dr Maron has collected over the years. Although the effort is admirable, that dataset is largely dependent on media reports, which is hardly a sound scientific methodology upon which to base policy. It is very hard to believe that those data are reliable as they attempt to collect deaths from the whole of the United States (more than 300 million). As such they can be considered, at best, the absolute minimum rather than an accurate estimate of the incidence of SCD in the US. The same limitations apply to the Israeli data by Steinvil et al. where the authors are basing their whole research and conclusions on a “systematic review” of two main newspapers.

Additional studies across Europe and the US that the authors should consider including in the review are studies in Ireland, Sweden and studies in young military recruits. For the benefit of the committee we provide a table summary with respective references.

Table 1: Summary of studies reporting the incidence of SCD and SADS in different young populations.
Country (Ref)

(Region)

 Studied population Nature of study Time period Age in years Incidence of SCD (SADS) per 100,000
USA1

(Olmsted county)

 General Prospective 1960-1989 20-40 3.6

 
USA2 Military recruits Retrospective 1977-2001 18-35 11.2

 
USA3 Military personnel Retrospective 1998-2008 18-35 3.5

 
Sweden4 General Retrospective 1992-1999 15-35 0.93

 
Denmark5 General Retrospective 2000-2006 1-35 2.8

 
Ireland6 General Retrospective 2005-2007 14-35 2.9

 
USA7

(Minnesota)

 High school athletes Retrospective 1985-1997 15-17 0.46

 
USA8 High school athletes Retrospective 2006-2007 14-17 4.4

 
Italy9

(Veneto)

 Athletes Prospective 1979-2004 12-35 1.9

 

 

  1. Incidence data in the UK: The section relating to the incidence of SCD in the UK is unfortunately inaccurate and incomplete. 1. The authors reference the database from the UK National Audit of Sudden Arrhythmic Death Syndrome and give the impression that within a period of four and a half years there were only 165 young deaths. The reader could justifiably infer that those numbers equate to less than 40 young deaths within the UK per annum, which is clearly not the case. Sudden Arrhythmic Death Syndrome (SADS) is only one aspect of young SCD. The term SADS is reserved for SCDs where the post-mortem fails to identify a cause of death and the heart appears structurally normal. Research has shown that a significant proportion of such deaths is due to inherited primary arrhythmia syndromes such as Long QT syndrome and Brugada Syndrome amongst others. So the terms SADS and SCD should not be used interchangeably. In addition, the SADS audit although initially an admirable initiative, it unfortunately failed to serve its purpose due to a number of reasons that I am sure the NSC committee identified during the initial consultation. As such the reported numbers are likely to be an underestimate of the true impact of SADS. 2. The authors refer to the study by Elston et al. It is important to highlight that the NSC commissioned this study and it was a “simulation” of the Italian data as published by Corrado et al. in the UK population. As such although the study may offer some insights to the potential impact of screening of young athletes in the UK, it should definitely not be used to quote incidence rates. 3. There is no reference to the most important UK data published to date (Papadakis M, et al. The magnitude of sudden cardiac death in the young: a death certificate-based review in England and Wales. Europace. 2009;11:1353-1358). It is hard to understand how this could be the case as this study refers to the issue under investigation by the authors and in the relevant population cohort. In that particular study we reported an incidence of SCD of 1.8 per 100,000 per year for England and Wales, alone, with SADS accounting only for 57 of the 419 (13.6%) SCDs annually. 4. Finally, in the same section the research paper by Wilson et al. is quoted. This paper reported on diagnostic rates after cardiac screening of conditions predisposing to SCD, not incidence rates of young SCD and does not belong in this section.
  2. Investigation and management of individuals identified through screening: This section lacks scientific rigor and the conclusions are false and misleading. The authors state in their key messages that “The conditions that lead to sudden cardiac death are poorly understood and there is no evidence to guide clinicians regarding treatment or lifestyle advice when such a problem is found in a family member or when detected at a screening examination.” The authors go on to quote the consensus statements form the American Heart Association, the American College of Cardiology and the European Society of Cardiology relating to the management of patients with ventricular arrhythmias and participation of athletes with cardiac disease in competitive sports. It is beyond the scope of our response to outline the relevant literature relating to the investigation and management of conditions implicated in young SCD. However, below are a few pertinent points: 1. Screening to reduce SCD in the young is indeed challenging as we are looking for more than one condition, some of which are fairly novel and lack evidence based management. 2. However, for most conditions there is reasonable evidence in the literature. Such conditions include Hypertrophic cardiomyopathy, Arrhythmogenic right ventricular cardiomyopathy, Dilated cardiomyopathy, Long QT syndrome, Cathecholaminergic polymorphic ventricular tachycardia, Brugada Syndrome and Accessory pathways (WPW), amongst others. 3. The fact that there are guidelines/recommendations for some of the conditions indicates that there is guidance for physicians who identify individuals with heart disease, irrespective of the level of evidence such recommendations are base on. 4. The conclusions of the review contradict the UK government. If indeed there is no established treatment then why did the Department of Health commission the 8th chapter of the National Service Framework for coronary heart disease, aimed at facilitating early identification of individuals at risk of SCD. That particular chapter states that “Quality requirement three: Sudden Cardiac Death. When sudden cardiac death occurs, NHS services have systems in place to identify family members at risk and provide personally tailored, sensitive and expert support, diagnosis, treatment, information and advice to close relatives.” It also states “Sudden cardiac death in younger people is often indicative of inherited cardiac disease. There is real potential to prevent further tragedies by the appropriate care of family members in these cases.” In line with these recommendations a number of specialists units, such as the one we run at St George’s Healthcare Trust have been created, in order to accommodate for the family needs, provide appropriate investigations, risk stratify individuals and prevent further SCDs.

 

Consistency or more explicit justification of recommendation differences between the NSC, Department of Health and NICE is imperative to avoid confusion of the public in general and health system stakeholders, policy and decision makers in particular.

 

  1. The different approaches to screening: In their conclusion the authors state that until further evidence is available the dichotomy between the American Heart Association and the Italian approach to screening is likely to remain unresolved. This statement is correct but it is important to highlight a few key points: 1. The American Heart Association approach to screening is not supported by any evidence whatsoever, while ECG based screening is. On the contrary, there are studies, even from Dr Maron, the chair of the recommendations committee, which suggest that most individuals are unlikely to benefit from the American Heart Association approach to screening. So the question based on the available scientific data is either no screening or screening utilizing the 12-lead ECG. 2. There are a number of studies, most included in your references, comparing the two models, which unanimously show that ECG based screening is the most cost-effective option of the two, identifying more individuals at risk at the expense of more people being subjected to investigations (higher false positive rate). 3. The AHA views do not represent the views of the whole US scientific community and this is reflected in their screening practice. Most of the professional sporting organisations and colleges follow the Italian protocol utilizing the 12-lead ECG. There are even charitable organisations, similar to Cardiac Risk in the Young, that perform ECG screening of young, physically active individuals in a large scale (Young Hearts for Life, http://www.yh4l.org/, Marek et al. Feasibility and findings of large-scale electrocardiographic screening in young adults: Data from 32,561 subjects. Heart Rhythm. 2011; 8:1555–1559).

 

  1. The test: 1. Although there is no doubt that the ECG, similarly to other screening tests, has its limitations, it is a simple, safe and validated test as required by the WHO and UKNSC criteria. Moreover, the ECG has been studied extensively as a screening tool, particularly in the UK, where our group amongst others has tested the ECG in young individuals of different gender, ethnicity, level of exercise and sporting discipline. Our group, through its extensive screening programme is leading the field, Internationally, and there are two clear recommendation documents from the ESC and the Seattle group that not only provide the clinician with clear recommendations of how to interpret an athlete’s ECG but are also accompanied by on-line training modules. For the benefit of the committee I have appended some of our seminal publications on ECG, all conducted in a British population (References 10-16, up till Jan 2014). 2. There are a number of studies referring to the sensitivity and specificity of the 12-lead ECG as a screening tool which are not referenced in the review. (References 17-23, up till Jan 2014). 3. The conclusions of the authors appear to be directly at odds with the NICE support for commissioning for transient loss of consciousness (http://www.nice.org.uk/guidance/sfcqs71/chapter/the-quality-statements-and-their-commissioning-and-resource-implications), which states that “A 12‑lead ECG is an important initial diagnostic test for identifying the likely cause of transient loss of consciousness in some people, and especially in predicting adverse events (for example, ECG abnormalities that are ‘red flag’ signs or symptoms may suggest structural heart disease or potential for arrhythmic syncope).”

 

  1. There should be evidence from high quality Randomised Controlled Trials that the screening programme is effective in reducing mortality or morbidity: We agree in principle with the authors that this is the ideal standard we should all aspire to. However, that standard is not always achievable in many aspects of science and life, in general. Sudden cardiac death in the young is thankfully not a common occurrence and the conditions that cause it are relatively rare. As such a large population would be required over decades to prove benefit. This is something we aspire to do through our CRY screening programme. However, it would be technically and ethically challenging to perform a large scale randomized controlled study, particularly in the light of the results of the 2006 Corrado et al. study and studies relating to the effective management of individuals identified with an inherited cardiac disease. In addition, in the UK, as is the case with most European countries and North America, there has been increasing demand for screening of young individuals. As such substantial parts of the population are being screened throughout the country. It would therefore be impossible to identify a large enough population, which is not being screened and will not be screened over the next decade.

 

This particular point has been discussed extensively on previous occasions with the NSC, as we feel that is unacceptable to fall back on the lack of randomized controlled trials as the basis for insufficient evidence. We would expect the NSC to be more explicit on what they would require from research to influence policy. If a randomized controlled trial is the standard they require, then commissioning regular reviews is a thankless task.

 

REFERENCES

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