1. ECG screening in asymptomatic children Delith Garrick

2. Aim To assess the use of ECG as a screening tool for causes sudden cardiac death in asymptomatic children

3. Case scenario

4. What conditions can be identified? Long QT syndrome Wolf Parkinson White Hypertrophic cardiomyopathy – ECG changes not detectable until late adolescent/ early adulthood

5. Options 1.Screening of those with known family history of sudden death. 2.Screening of young people involved in high level sport. 3.Screening of all young people.

6. Current standards No specific screening programme UK Italy – pre-participation screening including ECG for athletes 12-35yrs US – some universities do pre-participation screening for athletes Japan – mass screening of school age children including history, exam and ECG

7. Paper Electrocardiogram Screening for Disorders That Cause Sudden Cardiac Death in Asymptomatic Children: A Meta-analysis Rodday AM, Triedman JK, Alexander ME, Cohen JT, Ip S, Newburger JW, Parsons SK, Trikalinos TA, Wong JB and Leslie LK. Pediatrics 2012; 129(4).

8. Did the review address a clearly focused question? Q1 –P – Asymptomatic children and young adults (3-25 years) –I – ECG +/- Echo –C –O - Phenotypic (ECG or echo) prevalence of paediatric disorders associated with sudden cardiac death (HCM, LQTS, WPW) Q2 –P – Relatives of known cases –I – ECG +/- Echo –C – ‘Gold standard’ – eg Genetic test –O - Sensitivity, specificity and predictive value of ECG +/- echo What the paper did not address –If detection of these conditions prevents deaths –Cost effectiveness of screening

9. Did the authors look for the right type of papers? Yes

10. Do you think the important relevant studies were included? Limitations acknowledged in the discussion –Only MEDLINE articles used –Possible publication bias – eg studies that show poor diagnostic value may not have been included

11. Did the reviewers do enough to assess the quality of the studies included? Yes –Clear exclusion criteria –At least 2 researchers independently looked at each paper

12. If the results of the review have been combined was it reasonable to do so? Phenotypic prevalence estimates –Given for each condition by combining studies –Substantial heterogeneity between studies in each case (I 2 >90%, reaching statistical significance) Test value –Studies combined to give HSROCs showing variation of specificity with sensitivity for different test thresholds (separate curves for ECG +/- echo) –Estimated phenotypic prevalence then used to calculate PPV, NPV and numbers needed to screen

13. What are the overall results of the review? HCM –Phenotypic prevalence 45 per 100,000 (CI 10-79) –Maximal accuracy (Best point of combination of sensitivity and specificity) NPV 100%, PPV <1%, screen 2600 to detect 1, 400 false positives per case –Maximal specificity NPV 100%, PPV 2-21%, screen 4000 – 57000 to detect 1, 4 -57 false positives per case Echo or echo + ECG better than ECG alone

14. What are the overall results of the review? LQTS –Phenotypic prevalence 7 per 100,000 –Maximal accuracy (Best point of combination of sensitivity and specificity) NPV 100%, PPV <1%, screen 16000 to detect 1, 2000 false positives per case detected –Maximal specificity NPV 100%, PPV <1%, screen 135000 to detect 1, 135 false positives per case

15. What are the overall results of the review? WPW –Phenotypic prevalence 136 per 100,000 –Sensitivity and specificity not calculated as ECG is ‘gold standard’

16. Can the results be applied to the local population? Meta- analysis involved studies of general population of a number of different developed countries – no reason to suspect different findings locally

17. Were all outcomes considered? Yes

18. Are the benefits worth the harms and the costs? HCM + LQTS –Better sensitivity leads to high rate false positives – potential for anxiety –High specificity leads to large numbers screened for a few cases – potentially expensive HCM –Echo seems to be a much better test –What age to screen?

19. Summary and conclusion Case for setting up a screening programme not established by this meta-analysis Problems with screening for rare disease – large numbers screened to detect a few cases, potential for many false positives Further analysis needed to look at cost effectiveness of screening Study does not address whether screening will reduce cardiac death in young people