1. Cardivascular Causes of Sudden Infant Death
Alpay Çeliker M.D.
Hacettepe University
Pediatric Cardiology Department
Ankara, Türkiye

2. Sudden Infant Death Syndrome
Unexplained, unexpected death within the first year of life.There is no obvious cause of death on postmortem examination.
Postulated Hypotheses:
Abnormal brain stem respiratory control of arousal, dysautonomia, malignant cardiac arrhythmias
Risk Factors:
Prematurity, siblings of SIDS victim, maternal drug use, prone sleeping position, multiple gestations
Laboratory Tests:
EEG, Pulse oximetry, ECG, Holter, sleep studies, apnea monitorization

3. Causes of Cardiovascular Sudden Death
Children With Known Heart Disease
Aortic Stenosis
Congenital Heart Block
Cardiomyopathy & Myocarditis
Children With Unknown Heart Disease
Hypertrophic Cardiomyopathy
Long QT Syndrome
Wollf-Parkinson-White Syndrome
Primary Ventricular Tachycardia and Ventricular Fibrillation

4. Sudden Cardiac Death
VT & VF

5. VT VF

6. Polymorphic VT

7. Polimorphic Ventricular Tachycardia
Congenital Long QT Syndrome
Acquired Long QT Syndrome
Cathecolaminergic Polimorphic VT
Idiopatic VT & VF
Brugada Syndrome
Normal ECG (Belhassen)

8. Long QT Syndrome: Prevalence &History
On the basis of molecular genetics the prevalence of LQTS estimated to be one per births.
Description: 1957 (Jervell-Lange-Nielsen) and (Romano-Ward)
“Registry”: 1979 (Moss&Schwartz)
Genetic Analysis: 1991 (Keating)

9. Clinical Findings Syncope Family history ECG Findings Genetics
QT Interval Prolongation
Abnormal T Morphology
Prolonged QT Dispertion
T wave Alternans
Low Heart Rate
AV Blocks
Genetics
ECHO Findings

10. Syncope Attacks
Syncope occurs due to “torsade de pointes” or ventricular fibrillation.
Syncope develops during excitement or crying.
Especially during fear or excitement
Physical activity (swimming)
Syncope may occur during rest periods in LQTS3 type.

11. “Torsade de Pointes”
Polimorphic, twisted axis VT

12. Causes of Syncope

13. QT Interval
Corrected QT interval (QTc) can be measured by Bazzet formula.It should be measured from DII.
It is abnormal if prolonged >440 msec. It is more pronounced in sick girls. There are some cases with normal QT interval (abnormal genotype, normal fenotype).

14. Measurement of QTc Interval
Bazzet Formula
QTc= QT interval
RR
QTc= 0.52 second
1.21second
0.48 second or 480 milsec

15. Age and Sex & QTc (sec) 1-15 year Men Women Normal <0.44 <0.43
<0.45
Borderline
Prolonged
>0.47
>0.46
>0.48

16. T Morpholgy
There are changes in T wave morphology beside long QT interval.
T wave may be biphasic or humped. These findings are generally seen in V2-V5 leads, and prominent in V3 and V4.
This finding may be exaggrated after exercise test. Humps are generated by early after depolarization (EAD), and It is more common in symptomatic cases.

17. T Wave Changes
LQT3
LQT2
LQT1

18. Heart Rate Abnormalities
There is bradycardia. This feature is more apparent in children. Exercise test may also show inappropriately low heart rate increase.
There may be >1.2 second pause without marked sinus arrhythmia and this may provoke TdP. After pauses some may see humps at T wave.

19. Molecular Genetics *: sensoryneural deafness Type Gen
Inheritance
Gen
Gen & Ion Channel
Triggered causes
T Wave
LQT1 OD
11p5.5
KVLQT1, Iks
Stress, swimming
Wide T
LQT2
7q35-36
HERG, Ikr
Stress, fear
Twave with hump and low volume
LQT3
3p21-24
SCN5A, Na Channel
Sleeping
Normal, Late T
LQT4
4q25-27 ?
Sinusoidal T-U, AF
LQT5
21q22
KCNE1 (minK), Iks
LQT6
KCNE2 (MiRP1), Ikr
JLN* 1-2 OR
KCNE1, Ikr
*: sensoryneural deafness

20. Molecular Abnormalities in LQTS

21. Genetics I
Molecular analysis should be done in patients and their families.
Molecular analysis is very helpful in asymptomatic carriers.
Genetic analysis can reveal molecular diagnosis in percent of patients, since many of the genes responsible for LQTS have not been known nowadays. Molecular diagnosis may take several months.

22. Genetics II
Gene-specific treatment can be used after genetic analysis. In LQTS3, mexiletine (Na channel blocking agent) may lessen QT interval and attacks.
Incomplete penetration is very common.Ventricular arrhtyhmia can be seen in some conditions in these patients.
Some drugs may cause prolonged QT interval in these cases. QT interval would be normal if this drug will be stopped.

23. Incomplete Penetration

24. Diagnostic Criteria ECG FİNDİNGS: Points History Family History
QTc:
>480 ms ms
450 ms
Torsade de Pointes 2
T wave alternans 1
Humps at three ECG Leads 1
Low heart rate
History
Stress induced syncope 2
Syncope without stress 1
Congenital deafness
Family History
LQTS family cases 1
<30 year unexpected sudden death 0.5
<1 point: Low probability, 2-3 point: moderate probability LQTS,
>4 point: high probability LQTS

25. Treatment Permanent pacemaker implantation
 blockage
Permanent pacemaker implantation
Left Cardiac Sympatethic Denervation
ICD (Implantable Cardiac Defibrillator)
Gene specific treatment
Avoid of drugs that prolongs QT interval

26. Long QT ve Second Degree Type II AV Block

27. Drugs Should be Avoided !!!
Drugs causes QT Interval Prolongation:
Fenotiasins: Haldol, klorpromazin vs
Tricyclic Antidepressants: İmipramin, lityum
Makrolide Antibiotics: Erithromisin, azitromisin, cetocanazole
Nonsedative Antihystamins: Terfenadine, astemizol
Class I AA Drugs: Quinidin, procainamide, dysopyramide
Class III AA Drugs: Sotalol, amiodarone
Gastric Motility Agents: Cisapride
Stimulants
 stimulants, metylksantins, metilphenidate
Drug Abuse and Addicts
Nicotine, cocaine, amphetamine, marihuana, LSD, fensyklydine

28. Pentamidine
Procainamide
Hypokalemia

30. SIDS and Long QT Syndrome
Schwartz et al. demonstrated a correlation between QT prolongation and SIDS.!!!
In the first 48 hours there is a transient QT prolongation (fewer than two to three per 1000), secondary to fetal-maternal eletrolyte fluxes and transient alterations in autonomic control. ECG screening should be done after a few days of life.
The efficacy of therapeutic interventions in infants with prolonged QT interval is impossible to predict. Since many of these prolongations are due to transient autonomic instability.

31. Schwartz PJ. Et al.
Prolonged QT
And SIDS.
New Eng. J Med.
330; 709, 1998.

32. Schwartz PJ. Et al.Prolonged QT And SIDS.
Long QT and SIDS
healthy newborn enrolled and could be followed for one year.
12 lead ECG’s were obtained at the third or fourth day of life, and RR, QT and QTc intervals were measured from lead II.
1408 children were lost to follow-up when their families moved.
Schwartz PJ. Et al.Prolonged QT And SIDS.

33. There was no difference between SIDS and others regarding sex.
During one year of follow-up there were 34 deaths; 24 due to SIDS and 10 due to other causes.
The incidence of SIDS was 0.7 per Most deaths due to SIDS occurred in the second and third month of life.
There was no difference between SIDS and others regarding sex.
No victim of SIDS had a family history of LQTS.
Schwartz PJ. Et al.Prolonged QT And SIDS

34. ECG Findings Heart rate were not different between groups. QTc
SIDS: 43545 msec
NonSIDS Deaths: 39324 msec (p<0.05 )
Survivors: 40020 msec (p<0.05)
12 of 24 infants who died of SIDS (50 percent) had a QTc greater than 440 msec.
Schwartz PJ. Et al.Prolonged QT And SIDS

35. Schwartz PJ. Et al.Prolonged QT And SIDS

36. Schwartz et al. N Eng. J Med. 1999.
They showed SCN5A mutation in this resusiated sudden death case.

37. Prevention of SIDS Assessment of family history
ECG recordings at 2-3 weeks after birth.
If QTc> 470 msec after second ECG,  blockers may be used.
Schwartz PJ.

38.
!!!!???

39. Long QT Syndrome & SIDS Major Drawbacks
International studies have failed to demonstrate any excess of SIDS in families with known LQTS.
The incidence of SIDS is rare in some countries.
The incidence of sudden death decreased by changing of sleep position, cessation of parental smoking.
There is no proven relationship between the prolonged QT and molecular diagnosis.
Problems of screening methods.
There is no consensus on diagnosis and treatment.

40. Wolf-Parkinson-White Syndrome
The incidence in children is 0.1 %.
If there is a rapidly conducting accessory pathway, atrial fibrillation may cause to VF.
Some proarrhythmic (new arrhythmia caused by antiarrhythmic drugs) antiarrhythmic drugs may also cause this complication.

42. *
SVE

43. WPW Syndrome and VF
Atrial fibrillation is more common in patients with this syndrome.
If accessorry pathway refractory period is less than 220 msec, there is a risk of ventricular fibrillation during atrial fibrillation.
Some drugs, that prolongs AV conduction may provoke VF during AF due to rapid conduction via AP.

44. AF
Manifest WPW VF

45. Congenital Heart Block I
These babies have been diagnosed due to low heart rates. But most of them do not need pacemaker implantation. Close follow-up is mandatory to avoid the sudden cardiac death.
Pacemaker Indications (Class I):
No CHD, awake heart rate <65 bpm
CHD, awake heart rate <55 bpm
Heart failure
Prolonged QT Interval

46. Congenital Heart Block II
Mothers of babies with congeniatl AV block should be evaluated for antinuclear antibodies.
QT interval measurement is very important, since Long QT Syndrome may be the cause of AV block. Prolonged repolarisation results with AV block.

47. Complete Heart Block
QRS
QRS
QRS
*: P waves * * * * *

48. Permanent Pacemaker

49. Dilated Cardiomyopathy & Myocarditis
The etiology of DCM is idiopathic. Only 2-15 % of the children with DCM has biopsy proven myocarditis.
There are familial DCM cases.
Histologic features classically include myocyte hypertrophy, degeneration and varying degrees of interstitial fibrosis.
There is ventricular dilation and decreased left ventricular systolic function.

50. Dilated Cardiomyopathy

51. Dilated Cardiomyopathy & Myocarditis
Fibrosis of ventricular myocardium may occur, resulting in an irritable focus that causes ventricular arrhythmias.
In Holter monitoring 46 % of patients had arrhythmias. Ventricular arrhytmias are more common than atrial arrhythmias.
If there is a serious ventricular arrhythmia, amiodarone should be the drug of choice to prevent sudden death.

52. Myocarditis
Acute or myocarditis have been reported as pathologic findings in up to 42 % of patients with SCD.
Some patients may have subtle findings such as tachycardia and low-grade ventricular ectopy.
Occasionally AV block may develop during myocarditis.

54. Hypertrophic Cardiomyopathy
It is the most common hereditary cardiac disease.
Left ventricular outflow tract obstruction and diastolic dysfunction are the main pathophysiologic abnormalities.
The histologic features consistent with with HCM include myocyte hypertrophy with great variation in size and shape, cardiac muscle cell disarray, fibrosis and abnormalities of small intramural coronary arteries.

56. Hypertrophic Cardiomyopathy

57. Hypertrophic Cardiomyopathy
Muscle cell disarray may be a reason for ventricular arrhythmias.
Any kind of supraventricular and ventricular arrhythmias may occur in patients with HCM.
HCM is the most common cause of sudden cardiac death in young adults.
The prognosis of infants who present before one year of age continues to be dismal.
Amiodarone has been suggested as an effective medication for the treatment of rhythm problems. Sometimes ICD implantation is required to prevent sudden death due to VF.

58. Aortic Stenosis
The incidence of sudden death is 5.4 % in patients with AS.
The development of myocardial ischemia is thought to be the initiating factor for terminal ventricular arrhythmias in patients with severe AS.
Syncope, chest pain, dyspnea, left ventricular strain on ECG, severe LVOT obstruction were identified as risk factors for SCD.

59. Coronary Artery Anomalies
These anomalies may be diagnosed during postmortem examination.
Types of anomalies:
Anomalous origin of left coronary artery from pulmonary artery (ALCAPA)
Left main coronary artery from the right sinus Valsalva
Acute angle takeoff of a coronary artery
Intramural coronary artery
Single right coronary artery
ALCAPA is the mostcommon type that presents symptoms during infancy.