Syncope in children: how to pick the bad ones

More than 300 5-35 year olds die suddenly and unexpectedly each year in Australia,1,2 many with erroneous diagnoses prior to death- particularly epilepsy; we have to do better.There is now increasing evidence that about half such sudden deaths in young people are related to familial conditions, such as long QT syndrome, and CPVT (catecholaminergic polymorphic ventricular tachycardia) for which effective treatments are available.Syncope and funny turns occur in up to a quarter of all children. Clearly the vast majority are benign faints. So how can the clinician pick the bad ones? I present a few illustrative cases and draw some conclusions which may be helpful.

Case one

Click here to see Figure 1a     Click here to see Figure 1b

This 13 year old previously asymptomatic boy collapsed to the ground in a soccer game.

Lying on the ground he regained consciousness but looked pale and unwell. This ECG was obtained in casualty. (Figure 1a). His pulse was weak, very rapid and irregular. After electrical cardioversion (Figure 1b), there is overt pre-excitation, demonstrating the presence of an accessory pathway conducting from the atrium to the ventricle.

The ECG in Figure 1a, looks at first impression to show polymorphic ventricular tachycardia, but actually demonstrates atrial fibrillation in the presence of antegrade conduction down the accessory pathway.

Wolff-Parkinson-White syndrome (WPW) can present with cardiac arrest or syncope, secondary to atrial fibrillation, as well as the more common SVT. Catheter ablation of the pathway was arranged urgently.

Case two

Click here to see Figure 2

This six-year-old girl had a number of blackouts following pain, or when scared. Sometimes she would hold her breath before she blacked out.  She became upset when a Holter monitor was being fixed to her and had one of her typical blackouts. The Holter recording demonstrates bradycardia followed by the onset of 11 seconds of asystole.

This is a classical presentation of reflex anoxic seizures. The profound bradycardia and asystole is mediated by a huge vagal output. The long-term outlook is excellent and usually all that is required is reassurance and advice. This girl was advised to watch out for the early signs of dizziness and to lie flat on the ground until the symptoms past, and has done well. More severe forms respond to a dual chamber pacemaker. In the older child it is important to emphasise adequate hydration, salt and glucose input before, during and after exercise.

Case three

Click here to see Figure 3

This 11-year-old boy presented with sudden loss of consciousness when he became excited. Two years previously after swimming one length of a swimming pool he got out of the pool and fell down bruising on his face badly.  The maternal grandmother had had repeated episodes of loss of consciousness which stopped when she took a beta blocker for migraine. His 12 lead ECG and echocardiogram were normal. Concerned by the nature of the presentation, we implanted an implantable digital loop recorder- the “Reveal Plus” device -under the skin in the left parasternal region.³ This was activated by his mother when he had a typical collapse.

The ECG strip recorded from the Reveal device (Figure 3) demonstrates the onset of rapid polymorphic ventricular tachycardia which fortunately organised itself and returned back to sinus rhythm, whereupon he regained consciousness.

He has catecholaminergic polymorphic ventricular tachycardia (CPVT). This is usually an autosomal dominant inherited cardiac condition (affecting 50% of family members) linked to excessive calcium release in the cardiac cell triggered by adrenaline. The 12 lead ECG is normal, but ventricular extra beats or runs of VT are seen during exercise testing. It is highly lethal, but responds well to beta-blockers (as it did in the grandmother’s case). This boy has also received an intracardiac cardioverter defibrillator.

Case four

Click here to see Figure 4

An 11-year-old boy collapsed and died suddenly warming up for a game of hockey.

During life he had been diagnosed as epileptic. Despite his normal EEG, repeated episodes of sudden collapse during exercise (followed by seizures) and near drowning episodes, an ECG was never done by his neurologist.

A diagnosis was made after his death when the next door neighbour- a doctor- contacted me giving the history. A molecular genetic diagnosis of long QT syndrome was made from DNA extracted from his newborn screening card (Guthrie card). It was also found in his mother, who is now protected by beta blockers.⁴

His ECG in life would have looked something like that in Figure 4, where the QT interval is seen to be very long. The normal heart rate-corrected QT interval (QTc= QT interval divided by the square root of the preceding R-R interval) is less than 0.47 sec in females and 0.46 sec in males. It is best measured in lead 11 and V5.

Long QT syndrome (Romano Ward syndrome) is a group of conditions caused by defective potassium and sodium channels within the cardiac cell wall resulting in prolonged and abnormal repolarisation. Death occurs due to rapid ventricular tachycardia. Management involves beta blockers,⁵ and avoiding triggers, such as some medications (see http://www.qtdrugs.org/), competitive sport and swimming. Intracardiac cardioverter defibrillators are used in those at highest risk.

50% of family members will be gene carriers with varied level of risk, largely proportional to the length of the QT interval.^6-8 Family screening is essential.

Long QT syndrome and CPVT account for 10 to 15% of sudden infant deaths,⁹ and a similar proportion of those between one and 35 years of age.^10,11

Other conditions causing arrhythmic syncope in the young

Inherited cardiomyopathies are an important killer of young athletes- particularly hypertrophic cardiomyopathy (HCM),¹² with an incidence of 1 in 500, and arrhythmogenic right ventricular cardiomyopathy (ARVC).¹³ A family history may reveal young sudden deaths for some generations.

Warning signs in syncope

Features of the history suggesting an arrhythmic cause for syncope:

1. Relationship to exercise, particularly swimming.
2. Sudden onset.
3. No symptoms immediately prior to the collapse.
4. Facial injury (unconscious before hitting the ground).
5. Nocturnal seizures (In some conditions VT occurs with bradycardia)
6. Family history of sudden death in the young (less than 40 years of age) including sudden infant death.
7. Family history of recurrent syncope associated with exercise or excitement.*

(*Note: A family history of epilepsy is not reassuring; in fact it is the opposite. We have several families in whom familial epilepsy has erroneously been diagnosed when the cause of the problem has been long QT syndrome. Note also a positive tilt-table test does not exclude a malignant arrhythmia at other times!).

Conclusions

Clinical and family history are the two most important parts of the investigation of syncope in the young. An ECG may reveal WPW or Long QT syndrome, or features of hypertrophic or other cardiomyopathy. An exercise test and an echocardiogram are mandatory in exercise or excitement-triggered collapse. The implantable digital loop recorder is helpful when the history and other tests are inconclusive.

Any sudden death in a young person must be reported to the coroner, and proceed to a full forensic autopsy, with preservation of tissue suitable for DNA extraction.  If the post mortem is negative or a cardiomyopathy is found, family screening for inherited heart diseases should be done by a cardiac genetics service.¹⁴

Useful References

Websites

1. Practice Guidelines for the management of inherited (and other) cardiac diseases, from the Cardiac Society of Australia and New Zealand. www.medeserv.com.au/csanz/guidelines/practice/index.htm
2. Family support group for victims of sudden death: http://sads.org.au/sads/
3. New Zealand Cardiac Inherited Diseases Group: http://www.cidg.org/
4. Drugs to avoid in long QT syndrome: http://www.qtdrugs.org/

References quoted in this article

1. Doolan A, Langlois N, Semsarian C. Causes of sudden cardiac death in young Australians. Med J Aust. 2004; 180: 110-2.
2. Puranik R, Chow CK, Duflou JA, Kilborn MJ, McGuire MA. Sudden death in the young. Heart Rhythm. 2005; 2: 1277-82.
3. Kothari DS, Riddell F, Smith W, Voss J, Skinner JR. Digital implantable loop recorders in the investigation of syncope in children: benefits and limitations. Heart Rhythm. 2006; 3: 1306-12.
4. Skinner JR, Chong B, Fawkner M, Webster DR, Hegde M. Use of the newborn screening card to define cause of death in a 12-year-old diagnosed with epilepsy. J Paediatr Child Health. 2004; 40: 651-3.
5. Moss AJ, Zareba W, Hall WJ, Schwartz PJ, Crampton RS, Benhorin J, Vincent GM, Locati EH, Priori SG, Napolitano C, Medina A, Zhang L, Robinson JL, Timothy K, Towbin JA, Andrews ML. Effectiveness and Limitations of {beta}-Blocker Therapy in Congenital Long-QT Syndrome. Circulation. 2000; 101: 616-23.
6. Hobbs JB, Peterson DR, Moss AJ, McNitt S, Zareba W, Goldenberg I, Qi M, Robinson JL, Sauer AJ, Ackerman MJ, Benhorin J, Kaufman ES, Locati EH, Napolitano C, Priori SG, Towbin JA, Vincent GM, Zhang L. Risk of Aborted Cardiac Arrest or Sudden Cardiac Death During Adolescence in the Long-QT Syndrome. JAMA. 2006; 296: 1249-54.
7. Priori SG, Schwartz PJ, Napolitano C, Bloise R, Ronchetti E, Grillo M, Vicentini A, Spazzolini C, Nastoli J, Bottelli G, Folli R, Cappelletti D. Risk Stratification in the Long-QT Syndrome. N Engl J Med. 2003; 348: 1866-74.
8. Sauer AJ, Moss AJ, McNitt S, Peterson DR, Zareba W, Robinson JL, Qi M, Goldenberg I, Hobbs JB, Ackerman MJ, Benhorin J, Hall WJ, Kaufman ES, Locati EH, Napolitano C, Priori SG, Schwartz PJ,Towbin JA, Vincent GM, Zhang L. Long QT syndrome in adults. J Am Coll Cardiol. 2007; 49: 329-37.
9. Arnestad M, Crotti L, Rognum TO, Insolia R, Pedrazzini M, Ferrandi C, Vege A, Wang DW, Rhodes TE, George AL, Jr., Schwartz PJ. Prevalence of long-QT syndrome gene variants in sudden infant death syndrome. Circulation. 2007; 115: 361-7.
10. Tan HL, Hofman N, van Langen IM, van der Wal AC, Wilde AA. Sudden unexplained death: heritability and diagnostic yield of cardiological and genetic examination in surviving relatives. Circulation. 2005; 112: 207-13.
11. Tester DJ, Ackerman MJ. Postmortem long QT syndrome genetic testing for sudden unexplained death in the young. J Am Coll Cardiol. 2007; 49: 240-6.
12. Maron BJ. Hypertrophic cardiomyopathy. Circulation. 2002; 106: 2419-21.
13. Corrado D, Basso C, Thiene G. Arrhythmogenic right ventricular cardiomyopathy: diagnosis, prognosis, and treatment. Br Heart J. 2000; 83: 588-95.
14. Ingles J, Semsarian C. Sudden cardiac death in the young: a clinical genetic approach. Intern Med J. 2007; 37: 32-7.

Useful review articles

1. Francis J, Sankar V, Nair VK, Priori SG. Catecholaminergic polymorphic ventricular tachycardia. Heart Rhythm. 2005; 2(5): 550-4.
2. Goldenberg I, Moss AJ, Zareba W. Sudden cardiac death without structural heart disease: update on the long QT and Brugada syndromes. Curr Cardiol Rep. 2005; 7(5): 349-56.
3. Skinner JR.  Is there a link between SIDS and long QT interval?  Arch Dis Child 2005; 90: 445-449.

Article kindly contributed by: Dr Jonathan R. Skinner, MB ChB FRACP FRCPCH MD; Paediatric Cardiologist; Paediatric and Congential Cardiac Services; Auckland City Hospital; New Zealand; Editorial Advisory Board Member; Virtual Cardiac Centre; JSkinner@adhb.govt.nz
Jon Skinner is consultant paediatric cardiologist and arrhythmia specialist at the Starship Children’s and Auckland City Hospitals. He runs the national arrhythmia and pacing service for children in New Zealand. He is chairman of New Zealand’s national Cardiac Inherited Diseases Group (CIDG), and also of TRAGADY (trans-Tasman Response AGAinst sudden Death in the Young).  CIDG is sponsored by Cure Kids. New members of TRAGADY are welcome- contact Dr Skinner.