Journal Reading

Argadia Y.

Pembimbing :dr. Sri Lilijanti, SpA(K)

Dilated Cardiomyopathy

Disease of heart muscle :- Ventricular chamber enlargement (Dilated)

- Contractile dysfunction

CAUSEGenetic, Secondary to other cardiovascular

disease, infection, Toxic

Dilated CardiomyopathyIn Children

• Sudden Cardiac Death (SCD) is common in DCM adult

• Cause of death CHF• NEW treatment of

Implantable cardioverter-defibrillators (ICDs)

AHA recommended in DCM Adult with (LVEF) <35%

ADULT

Incidence : 0.57 cases / 100,000 childrenPoor Prognoses40% Need cardiac transplantation

(Towbin, et.al., 2006)

• 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 cardioverter-defibrillators (ICDs) option

Dilated CardiomyopathyIn Children

• To know the Sudden Cardiac Death (SCD) incidence in DCM children (larger multicenter cohort)

• To know the risk factor for SCD in DCM children

Objectives

METHOD

• Multicenter Study – PCMR (Pediatric Cardiomyopathy

Registry), North America

• Design– Retrospective if DCM diagnosed from

1990-1995– Cohort study if DCM diagnosed >1995

Criteria (at least 1) :

• Echocardiographic criteria for DCM left ventricular [LV] dilation

[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

• Unexpected death

• Occurring <1 h after the onset of a symptomatic cardiac event

Sudden Cardiac Death

Dilated Cardiomyopathy

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

• 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

DATA ANALYSIS– Descriptive Statistic risk factor

– Classification and Regression tree [CART]• To identify the high risk group

RESULT

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 Years16.7 Years

SUBJECTCHARACTERISTIC

Cause of DCM on Children

1286

255

13610 78 38

Idiopathic

Myocarditis

Neuromuscular

Malformation Syndrome

Familial Isolated Cardiomyopathy

Inborn Error of Metabolism

SCD(35)12%

Non-SCD

(189)68%

Unknow(56)20%

Death; 280; 16%

Alive; 1523; 84%

SCD = Suddent Cardiac Death

Mortality In ChildrenDCM

SCD All Other p SCD All Other pAge at diagnosis 4.7 ± 5.6 5.3 ± 6.1 0.738 Beta-blocker 0.09Male 54.3 53.5 0.88 Yes 2.9 7 Race / ethnicity 0.649 No 40 48 White 62.9 55.3 Unknow 57.1 45 Black 22.9 21 LV end-diastolic dimension Z-Score 4.2 ± 2.3 4.3 ± 2.4 0.928 Hispanic 11.4 16.9 LV end-systolic dimension Z-Score 5.9 ± 2.2 6.0 ± 2.5 0.883 Other 2.9 6.8 LV fractional shortening Z-Score -8.8 ± 2.5 -8.5 ± 3.4 Idiopathic 77.1 71.6 0.279 LV end-diastolic posterior wall thickness Z-

Score-1.1 ± 2.8 -0.5 ± 2.0 0.047

CHF at Diagnosis 86.7 72.6 0.031 NYHA functional class IV 0.139 LV end-diastolic septal wall thickness Z-

Score-1.1 ± 1.1 -0.8 ± 1.5 0.123

Yes 34.3 23.8 No 20 19.6 LV mass Z-Score 2.0 ± 2.7 2.3 ± 2.8 0.766 Unknow 45.7 56.5 LVEF Z-Score -6.9 ± 2.5 6.0 ± 2.4 0.123Familiy history of cardiomyopaty 0.551 Raw LVEF 23.3 ± 14.6 28.5 ± 13.7 0.073 yes 11.4 12.1 LVEF <35% 8 (80.0) 330 (67.8) 0.213 no 61.4 44.9 Raw LV fractional shortening (%) 15.3 ± 6.2 16.0 ± 8.3 0.298 unknow 37.1 43 LV fractional shortening <18% 27 (77.1) 1249 (73.0) 0.282Anticongestive therapy 0.905 Log (ratio of LV posterior wall thickness

end-diastolic dimension)-2.24 ± 0.38 -2.13 ± 0.32 0.016

Yes 5.7 6 No 54.3 52.7 Moderate to severe tricuspid regurgitation 0.078 Unknow 40 41.3 Yes 8.6 3.7 Antiarrhythmic therapy 0.025 No 14.3 26.3 Yes 20.0 12.1 Unknow 77.1 69.9 No 22.9 41.4 Moderate to severe mitral regurgitation 0.176 Unknow 57.1 46.5 Yes 14.3 9.3 ACE Inhibitor 0.023 No 11.4 20.9 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.

SCD All Other p SCD All Other pAge at diagnosis 4.7 ± 5.6 5.3 ± 6.1 0.738 Beta-blocker 0.09Male 54.3 53.5 0.88 Yes 2.9 7 Race / ethnicity 0.649 No 40 48 White 62.9 55.3 Unknow 57.1 45 Black 22.9 21 LV end-diastolic dimension Z-Score 4.2 ± 2.3 4.3 ± 2.4 0.928 Hispanic 11.4 16.9 LV end-systolic dimension Z-Score 5.9 ± 2.2 6.0 ± 2.5 0.883 Other 2.9 6.8 LV fractional shortening Z-Score -8.8 ± 2.5 -8.5 ± 3.4 Idiopathic 77.1 71.6 0.279 LV end-diastolic posterior wall thickness Z-

Score-1.1 ± 2.8 -0.5 ± 2.0 0.047

CHF at Diagnosis 86.7 72.6 0.031 NYHA functional class IV 0.139 LV end-diastolic septal wall thickness Z-

Score-1.1 ± 1.1 -0.8 ± 1.5 0.123

Yes 34.3 23.8 No 20 19.6 LV mass Z-Score 2.0 ± 2.7 2.3 ± 2.8 0.766 Unknow 45.7 56.5 LVEF Z-Score -6.9 ± 2.5 6.0 ± 2.4 0.123Familiy history of cardiomyopaty 0.551 Raw LVEF 23.3 ± 14.6 28.5 ± 13.7 0.073 yes 11.4 12.1 LVEF <35% 8 (80.0) 330 (67.8) 0.213 no 61.4 44.9 Raw LV fractional shortening (%) 15.3 ± 6.2 16.0 ± 8.3 0.298 unknow 37.1 43 LV fractional shortening <18% 27 (77.1) 1249 (73.0) 0.282Anticongestive therapy 0.375 Log (ratio of LV posterior wall thickness

end-diastolic dimension)-2.24 ± 0.38 -2.13 ± 0.32 0.016

Yes 5.7 6 No 54.3 52.7 Moderate to severe tricuspid regurgitation 0.078 Unknow 40 41.3 Yes 8.6 3.7 Antiarrhythmic therapy 0.025 No 14.3 26.3 Yes 20.0 12.1 Unknow 77.1 69.9 No 22.9 41.4 Moderate to severe mitral regurgitation 0.176 Unknow 57.1 46.5 Yes 14.3 9.3 ACE Inhibitor 0.023 No 11.4 20.9 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.

Transplantation

Non-SCD

SCD

DCM Survival

RISKSuddent Cardiac Death

FACTORPrediction From The Time of DCM Was Diagnosed

Associated No-Associated

• CHF at DCM diagnosis• Antiarrhythmic therapy• Lower Log (ratio of LV posterior wall

thickness end-diastolic dimension)• LV posterior wall thickness z-score

• Race• Sex• Cause of DCM• Family history of SCD or

cardiomyopaty• NYHA class• Anticongestive or B-blocker• Other echocardiograph finding

Multivariable CART Analysis

Prediction From The Time of DCM Was Diagnosed

HIGH RISK GROUP1. LV end-diastolic posterior wall

thickness z-score <-1.72. 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%.

Multivariable CART Analysis

Prediction From The Last Available Follow-up (64%)

HIGH RISK GROUPMeet 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%.

DISCUSSION

5 year Cumulative Incidence of SCD in children with DCM =

2.4 %

SCD INCIDENCE IN DCM CHILDREN

5 year Cumulative Incidence of SCD in

children with DCM = 2.4 %

SCD INCIDENCE IN DCM CHILDREN

CompareNo 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%)

INCHILDREN

DCM • SCD has lower incidence than adult• Death caused by progressive CHF is more

common• Children had fewer “ventricular arrhythmia”

5 year Cumulative Incidence of SCD in

children with DCM = 2.4 %

SCD INCIDENCE IN DCM CHILDREN

CompareNo 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%)

INCHILDREN

DCM • SCD has lower incidence than adult• Death caused by progressive CHF is more

common• Children had fewer “ventricular arrhythmia”

DIFFERENT NATURAL HISTORY THAN ADULT

DCM with SSD risk faktorConsidering for had ICDIMPLANTABLE CARDIOVERTER-DEFIBRILLATORS

(Criteria for ICD?)

First Diagnosed Last Available Follow-up

Prediction at Diagnosed Decision for ICD

DCM with SSD risk faktorConsidering for had ICDIMPLANTABLE CARDIOVERTER-DEFIBRILLATORS

(Criteria for ICD?)

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 wouldreceive an ICD at the time of diagnosis of cardiomyopathy

44% of subjects might receive an ICD

ICD For HighRisk Group of DCM ChildrenNot Yet Recommeded

Dubin et al (2003) :• incidence of inappropriate ICD discharge was 25%

Need further study for ICD safety

CRITICAL APPRAISAL

PICO

PICO

Children With Dilated Cardiomyopathy

High Risk Factor

No High Risk Factor

Sudden Cardiac Death

Are the results of this prognosis study valid?

1,083 defined sample

VA

LID

Defined and Representative

Sample

Long Follow-Up

Blind Outcome Criteria

Adjustment Important Factor

18 years folow-up

Sudden Cardiac Death(possible unblind)

2 subgroup criteria :- At diagnosed- Last Folow-up

Are the valid results of this prognosis study important?

SSD Cumulative Incidence Rate1-year 1.3%

3-year 2.0%

5-year 2.4%

(95% CI: 1.7% to 3.4%)

High Risk Group for SSD in DCM Children

At diagnosed

24 % had SSD

57% sensitivity and 78% specificity

Positive predictive value 5%, negative predictive value 99%

At last follow-up

44 % had SSD

86% sensitivity and 57% specificity

Positive predictive value 4%, negative predictive value 99%

Are the valid results of this prognosis study important?

High RiskN = 415

Non high Risk

N = 1332

SCD 20 15

Non-SCD 395 1317

OD RATIO 20 x 1317395 x 15

= 4.44

Can you apply this valid, important evidence about prognosis in caring for your patient?

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%

VALID IMPORTANT APLICABLE

CONCLUSION• SUDDEN CARDIAC DEATH IN CHILDREN WITH DILATED

CARDIOMYOPATHY HAD 5-YEAR CUMULATIVE INCIDENCE OF 2.4%

• DILATED CARDIOMYOPATHY CHILDREN WITH CRITERIA OF :First Diagnosed Last Available Follow-

up

1. LV end-diastolic posterior wall thickness z-score <-1.72. 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

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

HAD HIGH RISK OF SUDDEN CARDIAC DEATH

Recomendation• DILATED CARDIOMYOPATHY CHILDREN SHOULD BE DETECTED

FOR HIGH RISK GROUP• A HIGH RISK DILATED CARDIOMYOPATHY CHILDREN MAY

NEED IMPLANTABLE CARDIAC DEFIBRILATOR

THANK YOU

Implantable Cardiac Defibrillator