Pediatric Cardiomyopathy Registry

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Pediatric Cardiomyopathy Registry

• Etiology-specific Outcome in Pediatric
  Hypertrophic Cardiomyopathy

Steven D. Colan, M.D. Childrens Hospital Boston
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Co-Authors

• Gerry Cox, MD
• Steven Lipshultz, MD
• April Lowe, MS

• Paul Lurie, MD
• Lynn Sleeper, ScD
• Jeffrey Towbin, MD

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Conflict of Interest
No relationships to disclose
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Hypertrophic Cardiomyopathy

• Defined as ventricular hypertrophy without an
  identifiable hemodynamic cause
• Exists in pure and mixed forms, the latter
  having additional features such as ventricular
  dysfunction or noncompaction
• Etiology includes familial, metabolic disorders,
  neuromuscular disorders, malformation syndromes,
  and idiopathic

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Hypertrophic Cardiomyopathy in Children

• Available data are primarily derived from small,
  retrospective, single center studies
• Etiologically diverse but etiologic-specific
  incidence and outcomes are not known
• The Pediatric Cardiomyopathy Registry (PCMR) is a
  NIH-funded registry established in 1996 to assess
  the incidence and outcome of CM in children

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PCMR Methods

• Patients 0 to lt18 years at time of diagnosis
• Retrospectively-enrolled cohort1990-1995
• Prospectively-enrolled cohort 1996-present
• Comprehensive regional (New England and Central
  Southwest) data collection in prospective cohort
  for incidence data
• Longitudinal data collection in both groups for
  natural history and outcome data

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PCMR Longitudinal Data Collection

• Demographics
• Personal and family history
• Symptoms and therapy
• Laboratory data (ECG, ECHO, CATH, serum and
  tissue analysis, autopsy)
• Outcome

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Etiology-Specific Subgroups

• Inborn errors of metabolism (such as glycogen
  storage disease)
• Neuromuscular diseases (such as Friedreich
  ataxia)
• Malformation syndromes (such as Noonan syndrome)
• Sarcomeric HCM (genetically characterized
  sarcomeric defects)

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Other Subgroup Definitions

• 61 of cases are idiopathic
• Diverse etiology under age 1, gt age 1 most
  idiopathic cases have sarcomeric HCM
• We defined presumed sarcomeric HCM (pSHCM) as
  patients with genetically proven SHCM, lt1 yr with
  family history of HCM, or 1 yr with idiopathic
  HCM

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PCMR HCM Results

• Total 961 patients diagnosed with HCM at age
  lt18 years
• Pure HCM 855 children
• Mixed HCM 106 children
• This report focuses on the incidence and outcome
  data in the Pure HCM subgroup

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Results Etiology
Subgroup N ( )

• Inborn errors of metabolism 74 ( 9)
• Malformation syndromes 77 ( 9)
• Neuromuscular disorders 64 ( 7)
• Presumed sarcomeric HCM 557 (65)
• genetically proven (n115)
• family history HCM lt1 yr (n 6)
• idiopathic 1 yr (n 436)
• Idiopathic Infantile HCM (lt1 yr) 83 (10)

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Survival by Etiologic Subgroup
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Survival from Diagnosis by Age for All-cause HCM
Log rank plt0.001
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Age at Death for All HCM
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Survival from Diagnosis in pSHCM Grouped by Age
at Diagnosis
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Age at Death for pSHCM
100
90
80
70
60
Percentage
50
40
30
20
10
0
0
2
4
6
8
10
12
14
16
18
20
22
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Age at Death (years)
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pSHCM Predictors of Death

• 557 patients,18 (3) deaths
• Annual mortality 1
• Risk factor analysis (age race sex family
  history of CM or sudden death CHF LV size,
  function LV mass, septal thickness, wall
  thickness) None significant
• Limited Power due to few deaths

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HCM Diagnosed at Age lt1

• 328 patients total 1, 2, and 5 year survival
  post-CM diagnosis 76, 73, and 71
• 48 (15) Metabolic disorders
• 50 (15) Malformation syndromes
• 3 ( 1) Neuromuscular disorders
• 144 (44) presumed Sarcomeric HCM
• 83 (25) Idiopathic Infantile HCM

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Idiopathic Infantile HCM

• 83 patients, 1 year survival post-CM diagnosis of
  30
• Lack of an etiologic diagnosis and high incidence
  of death in this group seriously impedes our
  ability to calculate accurate etiologic-specific
  survival rates
• Patients who survive beyond age 1 but remain
  idiopathic have 2 and 5 year survivals of 97 and
  95

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Conclusions

• Infants without an etiologic disorder have the
  worst outcome
• Metabolic disorders and malformation syndromes
  have a worse outcome than neuromuscular disorders
  or pSHCM
• Annual mortality in pSHCM is 1, similar to the
  experience in adults with HCM