Transcript Cardivascular Causes of Sudden Infant Death

Cardivascular Causes of
Sudden Infant Death
Alpay Çeliker M.D.
Hacettepe University
Pediatric Cardiology Department
Ankara, Türkiye
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
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
Sudden Cardiac Death
ELECTRICAL DISORDERS
MYOCARDIAL DISORDERS
CONGENITAL ANOMALIES
LQTS
Myocarditis
Aortic Stenosis
Cathecolaminergic VT
Dilated Cardiomyopathy
Coronary Anomalies
Brugada Syndrome
Hypertrophic Cardiomyopathy
AV Blocks
WPW Syndrome
VT & VF
VT
VF
Polymorphic VT
Polimorphic Ventricular
Tachycardia
• Congenital Long QT Syndrome
• Acquired Long QT Syndrome
• Cathecolaminergic Polimorphic VT
• Idiopatic VT & VF
– Brugada Syndrome
– Normal ECG (Belhassen)
Long QT Syndrome:
Prevalence &History
• On the basis of molecular genetics the
prevalence of LQTS estimated to be one per
3000-4000 births.
• Description: 1957 (Jervell-Lange-Nielsen) and
1963-64 (Romano-Ward)
• “Registry”: 1979 (Moss&Schwartz)
• Genetic Analysis: 1991 (Keating)
Clinical Findings
• Syncope
• Family history
• ECG Findings
–
–
–
–
–
–
QT Interval Prolongation
Abnormal T Morphology
Prolonged QT Dispertion
T wave Alternans
Low Heart Rate
AV Blocks
• Genetics
• ECHO Findings
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.
“Torsade de Pointes”
Polimorphic, twisted axis VT
Causes of Syncope
100
80
60
STRESS
40
REST
20
0
LQT1
LQT2
LQT3
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).
Measurement of QTc Interval
R
Bazzet Formula
QTc= 0.52 second
1.21second
R
QTc= QT interval
RR
0.48 second or 480 milsec
Age and Sex & QTc (sec)
1-15 year
Men
Women
<0.44
<0.43
<0.45
Borderline 0.44-0.46
0.43-0.45
0.45-0.47
Prolonged
>0.46
>0.48
Normal
>0.47
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.
T Wave Changes
LQT3
LQT2
LQT1
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.
Molecular Genetics
Type
Gen
Gen & Ion Channel Triggered
causes
T Wave
LQT1 OD
11p5.5
KVLQT1, Iks
Wide T
LQT2 OD
7q35-36 HERG, Ikr
Stress, fear Twave with
hump and
low volume
LQT3 OD
3p21-24 SCN5A, Na
Channel
Sleeping
Normal,
Late T
LQT4 OD
4q25-27 ?
?
Sinusoidal
T-U, AF
LQT5 OD
21q22
KCNE1 (minK), Iks
?
?
LQT6 OD
21q22
KCNE2 (MiRP1),
Ikr
?
?
JLN*
1-2
11p5.5
21q22
KVLQT1, Iks
KCNE1, Ikr
?
?
Inheritan
ce
OR
Stress,
swimming
*: sensoryneural deafness
Molecular Abnormalities in
LQTS
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 30-50 percent of patients,
since many of the genes responsible for
LQTS have not been known nowadays.
Molecular diagnosis may take several
months.
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.
Incomplete Penetration
Diagnostic Criteria
• ECG FİNDİNGS:
– QTc:
• >480 ms
• 460-470 ms
• 450 ms
– Torsade de Pointes
– T wave alternans
– Humps at three ECG Leads
– Low heart rate
• History
Points
3
2
1
2
1
1
0.5
– Stress induced syncope
– Syncope without stress
– Congenital deafness
2
1
0.5
– LQTS family cases
– <30 year unexpected sudden death
1
0.5
• Family History
<1 point: Low probability, 2-3 point: moderate probability LQTS,
>4 point: high probability LQTS
Treatment
•  blockage
•
•
•
•
•
Permanent pacemaker implantation
Left Cardiac Sympatethic Denervation
ICD (Implantable Cardiac Defibrillator)
Gene specific treatment
Avoid of drugs that prolongs QT interval
Long QT ve Second Degree Type II AV
Block
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
Pentamidine
Procainamide
Hypokalemia
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.
Schwartz PJ. Et al.
Prolonged QT
And SIDS.
New Eng. J Med.
330; 709, 1998.
Long QT and SIDS
• 34.462 healthy newborn enrolled and
33.064 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.
• 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
1000. 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
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
440
430
420
410
400
390
380
370
Alive at 1
Year
Died of Other Died of SIDS
Causes
Schwartz PJ. Et al.Prolonged QT And SIDS
• Schwartz et al. N
Eng. J Med. 1999.
• They showed SCN5A
mutation in this
resusiated sudden
death case.
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.
-------------------
!!!!???
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.
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.
*
SVE
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.
AF
Manifest WPW
VF
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
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.
Complete Heart Block
QRS
QRS
QRS
* * * * *
*: P waves
Permanent Pacemaker
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.
Dilated Cardiomyopathy
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.
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.
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.
Hypertrophic Cardiomyopathy
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.
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.
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.