ATRIAL VOLUME: A NOVEL AND STRONG PREDICTOR OF SUDDEN CARDIAC DEATH IN HYPERTROPHIC CARDIOMYOPATHY

1
ATRIAL VOLUMEA NOVEL AND STRONG PREDICTOR OF
SUDDEN CARDIAC DEATH IN HYPERTROPHIC
CARDIOMYOPATHY

• Rod Pellenberg, Karen Texter, Susan Denfield,
• Nancy Ayres, Bryan Cannon, Jeffrey Towbin,
  Ricardo Pignatelli,
• J Lynn Jefferies, Jack Price, Jeffrey Kim, and
• Shuping Ge
• Baylor College of Medicine
• Texas Childrens Hospital
• Texas Heart Institute
• Houston, TX

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To An Athlete Dying Young

• The time you won your town the raceWe chaired
  you through the market-placeMan and boy stood
  cheering by,And home we brought you
  shoulder-high.To-day, the road all runners
  come,Shoulder-high we bring you home,And set
  you at your threshold down,Townsman of a stiller
  town.
• -Housman (1896)
• This is perhaps one of the most well-known poems
  pertaining to premature or early death in this
  case, that of a young man at the height of his
  physical glory

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Abstract

• Hypertrophic Cardiomyopathy (HCM) is the
  leading cause of Sudden Cardiac Death (SCD) in
  adolescents and young adults. To date, there are
  few reliable indicators of SCD risk in children
  with HCM. One purpose of our study was to
  identify echocardiographic risk factors that
  predict SCD in children with HCM. Recently, left
  atrial volume has been suggested to be a a useful
  measure for left ventricular diastolic function.
  Our study evaluated the relationship between LA
  size and clinical outcome in children with HCM.
  All children with HCM at Texas Childrens
  Hospital (1995-2007) were retrospectively
  reviewed. Using the apical four chamber view,
  atrial volumes were measured for three different
  groups of patients 1. personal history of SCD 2.
  family history of SCD. 3. no history of SCD.
  Our study results demonstrated that LA and RA
  are significantly enlarged in HCM pts with
  SCD/aborted SCD or a family history of SCD.
  Furthermore, a LA size of gt 34 cm3/m2 was shown
  to be strong predictor for SCD in HCM

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Epidemiology of HCM

• Between 1 in 500 and 1 in 1000 births could be
  affected by HCM
• Estimated that as many as 300,000 people in the
  United States have HCM
• HCM is nearly 7 times more common than Cystic
  Fibrosis
• Sudden Cardiac Death is the most feared
  complication of HCM

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SCD Risk Factors in HCM

• 2003 American College of Cardiology/European
  Society of Cardiology (ACC/ESC) consensus
  statement on the management of HCM identified
  seven major risk factors for SCD in HCM patients
• Prior cardiac arrest
• Spontaneous sustained VT
• Family history of SCD
• Syncope
• Asymptomatic NSVT
• Abnormal BP response to exercise (a decrease in
  systolic pressure of more than 20 mmHg)
• Extreme LVH ( 3 cm maximum wall thickness)

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Sudden Cardiac Death in Hypertrophic
Cardiomyopathy

• Hypertrophic Cardiomyopathy (HCM) is the leading
  cause of Sudden Cardiac Death (SCD) in
  adolescents and young adults
• To date, there are few reliable indicators of SCD
  risk in children with HCM
• Recently, left atrial volume has been suggested
  to be a a useful measure for left ventricular
  diastolic dysfunction
• Preliminary studies in our institution have
  suggested that left and right atrial enlargement
  on EKG are more common in children with HCM who
  experience a SCD event

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Cardiac Remodeling in HCM

• Left ventricular hypertrophy (posterior wall or
  interventricular septum hypertrophy)
• Hyperdynamic systolic function (measured by
  ejection or shortening fraction)
• Diastolic dysfunction is common
• Advanced HCM, may develop
• Thinning of the maximal left ventricular wall
  thickness
• LV enlargement
• LV systolic dysfunction

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Echocardiography and Outcome in HCM

• Studies have shown that tissue Doppler indices
  are lower in patients with HCM than in normal
  controls
• In adult patients with HCM, a transmitral to
  septal annular early diastolic ratio gt 15 is
  predictive of sudden death in adults with HCM
• In pediatric studies, a decrease in the septal
  annular velocity and increase in the ratio of
  transmitral early diastolic to septal anular
  annular velocity ratio is predictive of all cause
  mortality
• Lack of pediatric data with high sensitivity and
  specificity for predicting SCD

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Hypotheses

• 1) Atrial enlargement is an echocardiographic
  marker predictive of SCD
• 2) LV diastolic dysfunction is a significant risk
  factor
• 3) Newer echocardiographic indices of diastolic
  dysfunction can predict increased risk of SCD

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Objectives

• 1. To identify echocardiographic risk factors
  that predict SCD in children with HCM
• 2. To evaluate the relationship between LA size
  and clinical outcome in children with HCM

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Methods

• All children with HCM at Texas Childrens
  Hospital (1995-2007) were retrospectively
  reviewed
• A total of 47 children were included in the study
• Three groups were identified
• 1 Patients with a personal history of a SCD
  event (defined as a sudden unexpected
  cardiovascular collapse), either resuscitated or
  not resuscitated
• 2 Patients with a family history of SCD
  secondary to HCM
• 3 Patients with HCM without a personal or family
  history of SCD comprised our control group
• No pts in the SCD group had a family history of
  SCD

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Methods

• Demographic Data included
• Gender
• Body Surface Area (BSA)
• Age at Diagnosis
• Age at Echo
• Length of follow-up
• Clinical Data included
• Presence of an SCD event
• Age of SCD event
• Two-dimensional echocardiographic data included
• Left ventricular shortening fraction
• Presence and degree of left ventricular outflow
  tract obstruction (LVOT)
• Presence and degree of mitral regurgitation
• Pattern of hypertrophy (septal, apical,
  concentric)

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Exclusion Criteria

• A significant structural congenital heart defect
• Chronic atrial fibrillation
• Significant mitral regurgitation
• Noonans syndrome, an identified syndrome known
  to co-exist with HCM

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Atrial Volume Measurement

• Using the apical 4-chamber view, L and R atrial
  length and area were measured twice for each
  patient
• Using the average of the two measurements, atrial
  volume was calculated according to the area/
  length formula according to the ASE
  recommendations and adjusted for body surface
  area (BSA
• Volume 8xAreaxArea
• 3p L

.
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Statistical Analysis

• Demographic, clinical, and echocardiographic data
  between the three groups were analyzed using
• Students t-test
• ANOVA
• Chi-Square
• There was no difference in age at diagnosis, age
  at echo, length of follow-up, gender, body size,
  presence of LV outflow tract obstruction (LVOTO),
  degree of outflow tract obstruction, pattern of
  hypertrophy, or LV shortening fraction among the
  3 groups
• Only LA and RA volumes, among the variables that
  we studied, were significantly different in
  Groups 1 and 2 compared to Group 3

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Results Demographic Data
 
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Results Echocardiographic Data
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Atrial Volume/BSA
plt0.001




19
LA Volume/BSA SCD OutcomeROC Curve
AUC 0.9
sensitivity
LA size of 34 cm3 / m2 95 C.I.
(0.7-.98) Sensitivity 80 Specificity 97
1-specificity
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Results cont.

• By ROC analysis, an enlarged LA volume with a
  cutoff value of 34 cm3/m2 yielded 80 sensitivity
  and 97 specificity for occurrence of SCD.
• Using a Kaplan Meier survival curve for patients
  with LA size either greater or less than 34
  cm3/m2, there is a significant difference between
  the two groups.
• Only one patient who presented with SCD had LA
  size lt 34. Otherwise, there were no deaths
  throughout follow-up in patients with LAV lt 34.
• Looking five years forward , for patients with LA
  size gt 34, we see a survival to 50, although the
  95 confidence interval is large - 26. For
  patients with LA size lt 34, the survival is 96
  (95 confidence interval of 89-98.5)

21
Survival Curve Using Threshold of LA Volume 34
cm3/m2
95 C.I.
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Results Cont.
We then went back to our cutoff value of LA
volume gt 34 cm3/m2 to assess the accuracy of this
cutoff identifying patients with either a
personal Hx or a Family Hx of SCD as having
increased risk compared to those without a SCD
history.
Using a cutoff LA size of gt 34 cm3/m2, yields a
sensitivity of 85 and a specificity of 93 for
correctly identifying patients with a personal or
family history of SCD.
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Limitations

• Retrospective review
• Low incidence of SCD
• Single Plane measurements for atrial volume
  calculation
• Heterogenous disease process

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Conclusions

• LA and RA are significantly enlarged,
  representing biventricular diastolic dysfunction,
  in HCM pts with SCD/aborted SCD or a family
  history of SCD
• A LA size of gt 34 cm3/m2 is a strong predictor
  for SCD in HCM
• Further prospective study is warranted to confirm
  these findings and to develop strategies for
  individualized primary prevention of SCD in HCM

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Thank you.