Journal Critical TITLE WITH Incidence of and Risk Factors for Sudden Cardiac Death in Children With Dilated Cardiomyopathy

3. Disease of heart muscle :
- Ventricular chamber enlargement (Dilated)
- Contractile dysfunction
CAUSE
Genetic, Secondary to other cardiovascular
disease, infection, Toxic

4. Incidence : 0.57 cases / 100,000 children
Poor Prognoses
40%  Need cardiac transplantation
(Towbin, et.al., 2006)
ADULT
• Sudden Cardiac Death
(SCD) is common in DCM
adult
• Cause of death  CHF
• NEW treatment of
Implantable cardioverterdefibrillators (ICDs)
 AHA recommended in
DCM Adult with (LVEF)
<35%
• Lack information of DCM incidence and SCD
in LARGE population
• Lack information of SCD risk factor
• Need Information about high-risk child 
criteria for Implantable cardioverterdefibrillators (ICDs) option

5. Objectives
• To know the Sudden Cardiac Death (SCD)
incidence in DCM children
(larger multicenter cohort)
• To know the risk factor for SCD in DCM
children

7. • Multicenter Study
– PCMR (Pediatric Cardiomyopathy
Registry), North America
• Design
– Retrospective if DCM diagnosed from
1990-1995
– Cohort study if DCM diagnosed >1995

8. Criteria (at least 1) :
Dilated
Cardiomyopathy • Echocardiographic criteria
ventricular [LV] dilation
for DCM left
[i.e., LV end-diastolic dimension [EDD] > 2SD]
depressed LV systolic function [LV fractional shortening
or LVEF >2 SD
•
Pathologic findings consistent with DCM at
autopsy or by endomyocardial biopsy;
•
Other clinical evidence of DCM provided by
the cardiologist
Sudden Cardiac Death
•
Unexpected death
•
Occurring <1 h after the onset of
a symptomatic cardiac event

9. EXCLUSION CRITERIA
•
specific secondary causes of myocardial abnormalities
• Congenital heart disease
• Endocrine disorders known to cause myocardial damage
• chemotherapy or pharmacology-associated cardiotoxicity
• chronic arrhythmia,
• pulmonary parenchymal or
• Vascular disease,
• Immunologic disease

10. • Risk Factor :
– Demographic information, clinical evidence
of CHF, New York Heart Association
functional class, family history of
cardiomyopathy, medication classes, and
other therapies
– Echocardiographic measurements
•
•
•
•
•
•
LV EDD (Left Ventricular End-Diastolic Dimension)
LV end-systolic dimension,
LV fractional shortening,
LV septal and LV posterior wall thicknesses,
LV mass,
Tricuspid or mitral regurgitation

11. DATA ANALYSIS
– Descriptive Statistic  risk factor
– Classification and Regression tree
[CART]
• To identify the high risk group

12. RESULT

13. CHARACTERISTIC
Time
1990-2009
DCM case
1,803 cases
Mean age at diagnosis
5.3 ± 6.1 Years
Mean LV EDD z-score
4.3 ± 2,7
LV Fractional Shortening
16 ± 9 %
LFEF
28 ± 14%
Median Follow up (Patient With no Death or Transplatation Event)
Max
2.6 Years
16.7 Years

14. Cause of DCM on Children
136
10 78
38
Idiopathic
255
Myocarditis
Neuromuscular
Malformation Syndrome
1286
Familial Isolated
Cardiomyopathy
Inborn Error of Metabolism

15. DCM
Mortality In Children
Alive
1523
84%
Death
280
16%
SCD = Suddent Cardiac Death
Unknow
(56)
20%
Non-SCD
(189)
68%
SCD
(35)
12%

16. SCD
All Other
p
SCD
All Other
4.7 ± 5.6
5.3 ± 6.1
0.738
Age at diagnosis
Beta-blocker
54.3
53.5
0.88
Yes
2.9
7
Male
0.649
No
40
48
Race / ethnicity
White
62.9
55.3
Unknow
57.1
45
Black
22.9
21
4.2 ± 2.3
4.3 ± 2.4
LV end-diastolic dimension Z-Score
Hispanic
11.4
16.9
5.9 ± 2.2
6.0 ± 2.5
LV end-systolic dimension Z-Score
Other
2.9
6.8
-8.8 ± 2.5
-8.5 ± 3.4
LV fractional shortening Z-Score
77.1
71.6
0.279
Idiopathic
LV end-diastolic posterior wall thickness Z-1.1 ± 2.8
-0.5 ± 2.0
Score
86.7
72.6
0.031
CHF at Diagnosis
0.139
NYHA functional class IV
LV end-diastolic septal wall thickness Z-1.1 ± 1.1
-0.8 ± 1.5
Score
Yes
34.3
23.8
No
20
19.6
2.0 ± 2.7
2.3 ± 2.8
LV mass Z-Score
Unknow
45.7
56.5
-6.9 ± 2.5
6.0 ± 2.4
LVEF Z-Score
0.551
23.3 ± 14.6 28.5 ± 13.7
Familiy history of cardiomyopaty
Raw LVEF
yes
11.4
12.1
8 (80.0)
330 (67.8)
LVEF <35%
no
61.4
44.9
15.3 ± 6.2
16.0 ± 8.3
Raw LV fractional shortening (%)
unknow
37.1
43
27 (77.1)
1249 (73.0)
LV fractional shortening <18%
0.905
Anticongestive therapy
Log (ratio of LV posterior wall thickness
-2.24 ± 0.38 -2.13 ± 0.32
end-diastolic dimension)
Yes
5.7
6
No
54.3
52.7
Moderate to severe tricuspid regurgitation
Unknow
40
41.3
Yes
8.6
3.7
0.025
No
14.3
26.3
Antiarrhythmic therapy
Yes
20.0
12.1
Unknow
77.1
69.9
No
22.9
41.4
Moderate to severe mitral regurgitation
Unknow
57.1
46.5
Yes
14.3
9.3
0.023
No
11.4
20.9
ACE Inhibitor
Yes
20
38.3
Unknow
74.3
69.9
No
22.9
18.5
Unknow
57.1
43.2
ACE : angiotensin-converting enzyme; CHF : congestive heart failure; CI : confidence interval; LV : left ventricular; LVEF : left ventricular
ejection fraction; NYHA : New York Heart Association; SCD : sudden cardiac death.
p
0.09
0.928
0.883
0.047
0.123
0.766
0.123
0.073
0.213
0.298
0.282
0.016
0.078
0.176

17. SCD
All Other
p
SCD
All Other
4.7 ± 5.6
5.3 ± 6.1
0.738
Age at diagnosis
Beta-blocker
54.3
53.5
0.88
Yes
2.9
7
Male
0.649
No
40
48
Race / ethnicity
White
62.9
55.3
Unknow
57.1
45
Black
22.9
21
4.2 ± 2.3
4.3 ± 2.4
LV end-diastolic dimension Z-Score
Hispanic
11.4
16.9
5.9 ± 2.2
6.0 ± 2.5
LV end-systolic dimension Z-Score
Other
2.9
6.8
-8.8 ± 2.5
-8.5 ± 3.4
LV fractional shortening Z-Score
77.1
71.6
0.279
Idiopathic
LV end-diastolic posterior wall thickness Z-1.1 ± 2.8
-0.5 ± 2.0
Score
86.7
72.6
0.031
CHF at Diagnosis
0.139
NYHA functional class IV
LV end-diastolic septal wall thickness Z-1.1 ± 1.1
-0.8 ± 1.5
Score
Yes
34.3
23.8
No
20
19.6
2.0 ± 2.7
2.3 ± 2.8
LV mass Z-Score
Unknow
45.7
56.5
-6.9 ± 2.5
6.0 ± 2.4
LVEF Z-Score
0.551
23.3 ± 14.6 28.5 ± 13.7
Familiy history of cardiomyopaty
Raw LVEF
yes
11.4
12.1
8 (80.0)
330 (67.8)
LVEF <35%
no
61.4
44.9
15.3 ± 6.2
16.0 ± 8.3
Raw LV fractional shortening (%)
unknow
37.1
43
27 (77.1)
1249 (73.0)
LV fractional shortening <18%
0.375
Anticongestive therapy
Log (ratio of LV posterior wall thickness
-2.24 ± 0.38 -2.13 ± 0.32
end-diastolic dimension)
Yes
5.7
6
No
54.3
52.7
Moderate to severe tricuspid regurgitation
Unknow
40
41.3
Yes
8.6
3.7
0.025
No
14.3
26.3
Antiarrhythmic therapy
Yes
20.0
12.1
Unknow
77.1
69.9
No
22.9
41.4
Moderate to severe mitral regurgitation
Unknow
57.1
46.5
Yes
14.3
9.3
0.023
No
11.4
20.9
ACE Inhibitor
Yes
20
38.3
Unknow
74.3
69.9
No
22.9
18.5
Unknow
57.1
43.2
ACE : angiotensin-converting enzyme; CHF : congestive heart failure; CI : confidence interval; LV : left ventricular; LVEF : left ventricular
ejection fraction; NYHA : New York Heart Association; SCD : sudden cardiac death.
p
0.09
0.928
0.883
0.047
0.123
0.766
0.123
0.073
0.213
0.298
0.282
0.016
0.078
0.176

18. DCM Survival
Transplantation
Non-SCD
SCD

19. RISK
FACTOR
Associated
• CHF at DCM diagnosis
• Antiarrhythmic therapy
• Lower Log (ratio of LV posterior wall
thickness end-diastolic dimension)
• LV posterior wall thickness z-score
No-Associated
•
•
•
•
Race
Sex
Cause of DCM
Family history of SCD or
cardiomyopaty
• NYHA class
• Anticongestive or B-blocker
• Other echocardiograph finding

20. Prediction From The Time of DCM Was
Diagnosed
HIGH RISK GROUP
1. LV end-diastolic posterior wall
thickness z-score <-1.7
2. Group with :
• LV end-diastolic posterior
wall thickness z-score >-1.7
• Age at diagnosis < 13.1 yo
• Septal thickness z-score 0.8,
• Using antiarrhythmic
therapy within a month of
presentation with DCM
57% sensitivity and 78% specificity.
Positive predictive value (percentage of % SCD among those identified as high risk) = 5%,
Negative predictive value (percentage of non-SCD among those identified as lower risk) = 99%.

21. Prediction From The Last Available
Follow-up (64%)
HIGH RISK GROUP
Meet 3 following criteria
• LV end-systolic dimension z-score
>2.6;
• DCM diagnosis at age younger
than 14.3 years;
• LVPWT:EDD ratio <0.14
86% sensitivity and 57% specificity.
Positive predictive value (percentage of % SCD among those identified as high risk) = 4%,
Negative predictive value (percentage of non-SCD among those identified as lower risk) = 99%.

22. DISCUSSION

23. 5 year Cumulative Incidence of SCD in
children with DCM =
2.4 %

24. 5 year Cumulative Incidence of SCD in
children with DCM = 2.4
%
Compare
No
Author
Years
Result
1
Dimas vv, et al
2009
2
Rhee, et al.,
2007
Incidence SCD in DCM children and Congenital Heart Disease was
3
Shekha K., et al
2005
[ADULT] SCD in DCM adult was
4
Kadish, et al.
2004
[ADULT] SCD occurred in
DCM
IN
CHILDREN
DCM children, died suddenly
of 458 adults with DCM (with LVEF 36%)
• SCD has lower incidence than adult
• Death caused by progressive CHF is more
common
• Children had fewer “ventricular arrhythmia”

25. 5 year Cumulative Incidence of SCD in
children with DCM = 2.4
%
Compare
No
Author
Years
Result
1
Dimas vv, et al
2009
1% DCM children, died suddenly
2
Rhee, et al.,
2007
Incidence SCD in DCM children and Congenital Heart Disease was 1.3
3
Shekha K., et al
2005
[ADULT] SCD in DCM adult was low
4
Kadish, et al.
2004
[ADULT] SCD occurred in 7.4% of 458 adults with DCM (with LVEF 36%)
DCM
IN
CHILDREN
%
• SCD has lower incidence than adult
• Death caused by progressive CHF is more
common
• Children had fewer “ventricular arrhythmia”
DIFFERENT NATURAL HISTORY THAN
ADULT

26. First Diagnosed
Prediction at Diagnosed
Last Available Follow-up
Decision for ICD

27. First Diagnosed
Last Available Follow-up
Prediction at Diagnosed
Decision for ICD
1. LV end-diastolic posterior wall
thickness z-score <-1.7
2. Group with :
• LV end-diastolic posterior
wall thickness z-score >-1.7
• Age at diagnosis < 13.1 yo
• Septal thickness z-score 0.8,
• Using antiarrhythmic therapy
within a month of
presentation with DCM
Meet 3 following criteria
• LV end-systolic dimension z-score
>2.6;
• DCM diagnosis at age younger than
14.3 years;
• LVPWT:EDD ratio <0.14
24% of children with DCM would
receive an ICD at the time of diagnosis
of cardiomyopathy
44% of subjects might receive an ICD

28. Not Yet Recommeded
Dubin et al (2003) :
• incidence of inappropriate ICD discharge was 25%
Need further study for ICD safety

30. Children With Dilated Cardiomyopathy
High Risk Factor
No High Risk Factor
Sudden Cardiac Death

31. VALID
Defined and
Representative Sample
Long Follow-Up
Blind Outcome Criteria
Adjustment Important
Factor

32. 1-year
1.3%
3-year
2.0%
5-year
2.4%
(95% CI: 1.7% to 3.4%)
24 % had SSD
57% sensitivity and 78% specificity
Positive predictive value 5%, negative predictive value 99%
44 % had SSD
86% sensitivity and 57% specificity
Positive predictive value 4%, negative predictive value 99%

33. High Risk
N = 415
SCD
Non-SCD
20
395
OD RATIO
20 x 1317 = 4.44
395 x 15
Non high
Risk
N = 1332
15
1317

34. Mean age at diagnosis
5.3 ± 6.1 Years
Mean LV EDD z-score
4.3 ± 2,7
LV Fractional Shortening
16 ± 9 %
LFEF
28 ± 14%

35. First Diagnosed
1.
2.
LV end-diastolic posterior wall thickness z-score <-1.7
Group with :
•
LV end-diastolic posterior wall thickness z-score >-1.7
•
Age at diagnosis < 13.1 years old
•
Septal thickness z-score 0.8,
•
Using antiarrhythmic therapy within a month of
presentation with DCM
Last Available Follow-up
Meet 3 following criteria
• LV end-systolic dimension zscore >2.6;
• DCM diagnosis at age younger
than 14.3 years;
• LVPWT:EDD ratio <0.14