Download Assessment of Cardiac Function in Duchenne Muscular Dystrophy

Assessment of Cardiac Function in Duchenne
Muscular Dystrophy
The Cincinnati Experience
Parent Project Muscular Dystrophy
2011 CONNECT Conference
Kan N. Hor, MD
The Heart Institute
Cincinnati Children’s Hospital
Assessment of Cardiac Function in Duchenne
Muscular Dystrophy
The Cincinnati Experience
Parent Project Muscular Dystrophy
2011 CONNECT Conference
Kan N. Hor, MD
The Heart Institute
Cincinnati Children’s Hospital
No Relationships to
Disclose
Duchenne muscular dystrophy (DMD)
  Incidence 1:3500 live male births
  X linked skeletal and cardiac myopathy
  Most frequently inherited muscular
dystrophy
  Deficiency in dystrophin protein leads to
skeletal and cardiac findings
Duchenne muscular dystrophy (DMD)
The Heart in DMD
  Heart failure symptoms often go
unrecognized secondary to physical
inactivity due to skeletal muscle disease
  Symptoms of cardiac dysfunction can be
vague and non-specific
The Heart in DMD
  Currently most patients come to the
attention of the cardiologist late in the
disease process
  Proactive approach is needed
  Get to patients early
  Stimulate research to change cardiac the
outcome with evidence base practice
  Enhance both duration and quality of life
The Heart in DMD: How the Heart Squeeze
The Heart in DMD: How the Heart Squeeze
The Heart in DMD: How the Heart Squeeze
The Heart in DMD: How the Heart Squeeze
The Heart in DMD: Beyond Squeezing
The Heart in DMD: Beyond Squeezing
The Heart in DMD: Beyond Squeezing
The Heart in DMD: Beyond Squeezing
The Heart in DMD: Beyond Squeezing
Puchalski et al, Int J Cardiovasc Imaging, 2009
Silva et al, JACC 2007
The Heart in DMD: Beyond Squeezing
Hor et al, unpublished data
The Heart in DMD: Beyond Squeezing
The Heart in DMD: Beyond Squeezing
The Heart in DMD: Beyond Squeezing
The Heart in DMD: Beyond Squeezing
Normal
DMD
DMD
DMD
The Heart in DMD: Beyond Squeezing
The Heart in DMD: Beyond Squeezing
The Heart in DMD: Beyond Squeezing
•  Cardiac contraction is a bit
more complicated than may
be understood just by
looking at ejection fractions
  Circumferential fiber tracts
Robb JS AHJ 1942
  results in circumferential and
radial shortening
  Oblique fiber tracts
  results in ventricular twist, or
“torsion”
Sengupta JACC 2006
The Heart in DMD: Beyond Squeezing
Duchenne muscular dystrophy (DMD)
Adapted from Nael Osman, PhD
Background: Concept of Strain
•  Motion: Velocity and Displacement
•  Deformation: Strain (circumferential,
radial and longitudinal)
displacement
Circumferential
Strain
Radial Strain
The Heart in DMD: Beyond Squeezing
Myocardial Tagged Imaging different disease stage
The Heart in DMD: Beyond Squeezing
The Heart in DMD: Beyond Squeezing
DMD Patient
Control Subject
The Heart in DMD: Beyond Squeezing
A = Control subjects age match to DMD boys
B = DMD < 10 Years with normal EF
C = DMD > 10 Years with abnormal EF
D = DMD > 10 Years with abnormal EF but no fibrosis
E = DMD > 10 Years with abnormal EF with fibrosis
The Heart in DMD: Beyond Squeezing
The Heart in DMD: Beyond Squeezing
Hor et al, JACC 2009
The Heart in DMD: Beyond Squeezing
  Serial strain over a 12 – 14 month period
showed decline in all boys
  Ejection fraction in the same period were
more variable
  Serial circumferential strain more sensitive
Ejection Fraction
Circumferential Strain
Hagenbuch et al Am J Cardiol 2010
The Heart in DMD: Summary
  Ventricular function may be more
complex than can be described by
“traditional” functional indices such as
ejection fraction
  Our studies show that strain is more
sensitive than ejection fraction and
detects occult disease before global EF
decline
  What’s next??
The Heart in DMD: Summary
  Need to prove that strain is more reliable and
sensitive indicator of cardiac dysfunction
  Need to combine with myocardial
characteristics such as myocardial fibrosis
  Prove that strain not only predict presence of
heart disease early but that it can predict
development of fibrosis/scar
  Need a means to detect disease before overt
cardiac disease
The Heart in DMD: Summary
  Many great cardiac drug trials going on
  Do we have the right tool to assess efficacy?
  Do we have a more sensitive tool to assess
cardiac dysfunction than ejection fraction?
  Until then great drug trials for cardiac
disease rely on a tool that is just not that
sensitive
The Heart in DMD: Summary
  So is circumferential strain ready for
prime time?
  Need to critically prove with larger
studies over longer period of time so
there is clear evidence
  Need to think out of the box and move
from status quo practice
  Before we treat cardiac issues we need a
sensitive and reliable tool
The Heart in DMD: Summary
  The future of the boys depend on
developing the right tool to tells us that
the treatment is effective or even if it is
harmful
  We should demand such high quality
ability to assess the effectiveness of drug
therapy
  In conjunction with PPMD, clinical and
basic scientist can achieve this goal
Acknowledgements